Nutrigenetics for weight loss | 703-844-0184 | Optifast | Nutrimed weight loss | Fairfax, Va 22306 | Dr. Sendi

Nutrigenetics 2018:

Goldilocks: “like porridge, leptin needs to be juuuuust right.”

Leptin is a hormone secreted primarily in white adipose fat cells and plays a role in regulating energy balance by curbing or stimulating hunger.  Often referred to as the “satiety hormone,” leptin works by signaling the need to start or stop eating. In the short term, as fat supplies are reduced, leptin levels drop to signal when enough food has been consumed per meal.

Leptin levels vary exponentially, not linearly, with fat mass.1,2  White fat, or white adipose tissue, is traditionally linked to the development of obesity, heart disease and diabetes, because it stores up calories, in contrast to brown fat which burns calories to generate heat.

Leptin also works on a more seasonal basis. Leptin is released from the body’s fat base and is a longer term signaling mechanism to indicate when it is time to build more fat supplies to ensure survival. If fat supplies are adequate, then leptin levels will be high. If fat supplies are low, then the corresponding lower leptin levels will signal that it is time to eat carbohydrates to rebuild fat supplies. This is a natural metabolic feedback mechanism that plays out for multiple species.

It is possible however for the body to become leptin resistant, just as it is possible to become insulin resistant.  High circulating levels of leptin can result in downregulation of leptin receptors. As a result, the elevated levels of leptin fail to signal the need to stop eating.  Over eating and the associated incremental weight gain is common with leptin resistance.

The SH2B adapter protein 1 (SH2B1) has been identified as a positive regulator of insulin, IGF–1 and leptin action.4-7 It is well known that insulin’s primary role is to regulate glucose and lipid metabolism. SH2B1 deletion results in marked insulin and leptin resistance, obesity, and type 2 diabetes in mice as well as humans, indicating that SH2B1is required for the maintenance of normal body weight, insulin sensitivity, and glucose metabolism.7-12 In addition, it has been consistently demonstrated that SNPs in the SH2B1 gene are associated with obesity and/or BMI. The rs7498665 SNP of the SH2B1 gene, which is included in the Kashi Health Weight Management Genetic Panel, results in the non-synonymous amino acid exchange Thr484Ala in a splice variant-independent position with low conservation. The association of increased BMI with SH2B1 SNP (rs7498665 and/or rs7359397) risk alleles has been robustly replicated in a study of 249,796 individuals of European ancestry,13 and in 34,416 subjects of various ethnicities14.  Another study, conducted in 1,700 Dutch women, 15demonstrated that the risk allele at rs7498665 was associated with increased intake of total fat (per allele effect: 1.08 g/d), saturated fat (per allele effect: 0.60 g/d) and monounsaturated fat (per allele effect: 0.37 g/d). These results suggest that consumption of a diet high in fat, and particularly a diet high in saturated fat, places people who possess the SH2B1 risk allele at a greater risk of obesity.

The Kashi Health Weight Management Panel provides valuable genetic data so providers can offer the best guidance to each patient on the ideal diet approaches for individualized weight loss goals.  The lifestyle recommendations support this work by identifying key eating and exercise strategies.


  1. Lönnqvist F, Arner P, Nordfors L, Schalling M (1995). “Overexpression of the obese (ob) gene in adipose tissue of human obese subjects”. Nat. Med. 1 (9): 950–3. doi:10.1038/nm0995-950. PMID 7585223.
  2. Madej T (1998). “Considerations in the use of lipid-based drug products”. J Intraven Nurs. 21 (6): 326. PMID 10392096.
  3. J Clin Endocrinol Metab. 2000 Aug;85(8):2685-91. Twenty-four-hour leptin levels respond to cumulative short-term energy imbalance and predict subsequent intake. Chin-Chance C1, Polonsky KS, Schoeller DA.
  4. Kotani K et al. SH2-B alpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase. Biochem. J. 1998;335:103–109
  5. Maures TJ et al. SH2B1(SH2–B) and JAK2: a multifunctional adaptor protein and kinase made for each other. Trends Endocrinol Metab. 2007;18: 38–45
  6. Morris DL et al. SH2B1 enhances insulin sensitivity by both stimulating the insulin receptor and inhibiting tyrosine dephosphorylation of insulin receptor substrate proteins. Diabetes. 2009;58:2039-2047
  7. Ren D et al. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest 2007;117:397–406
  8. Duan C et al. Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. Mol Cell Biol 2004;24:7435–7443
  9. Ren D et al. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metabolism. 2005;2:95–104
  10. Li M et al. Differential role of SH2-B and APS in regulating energy and glucose homeostasis. Endocrinology. 2006;147: 2163–2170
  11. Bochukova EG et al. Large, rare chromosomal deletions associated with severe early onset obesity. Nature. 2010;463:666–670
  12. Walters RG et al. A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature. 2010;463:671–67597.
  13. Speliotes EK et al. Association analyses of 249,796 individuals reveal eighteen new loci associated with body mass index. Nat Genet. 2010;42:937–948
  14. Thorleifsson G et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009;41:18–24
  15. Bauer F et al. Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr. 2009;90:951–959

Call 503-206-4989 to order the free Weight Management Poster, request patient education brochures, and begin using this informative tool in your practice.


Kashi Health References


  1. Liu CCI, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol.  2013 Feb 9 (2):106-18.  Doi: 10.1038/nrneurol. 2012.263.
  2. Shankar GM, Li S Mehta TH, Garcia-Munoz A., Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA Regan CM, Walsh DM, Sabatinis BL, Selkoe DJ (Aug 2008). “Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory”. Nature Medicine. 14 (8): 837-42. dol:10.1038/nm1782.
  3. Prelli F, Castario E., Glenner GG, Frangione B (Aug 1988). “Differences between vascular and plaque core amyloid in Alzheimer’s disease”.  Journal of Neurochemistry.  51 (2):648-51.  Doi:10.1111/j.1471-4159.1988.tb01087.x.
  4. Harold, D. et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet. 41, 1088-1093 (2009).
  5. Lambert, J.C. et al Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease.   Genet.41, 1094-1099 (2009).

Behavioral Health

  1. Woo JM et al. The association between panic disorder and the L/L genotype of catechol-O-methyltransferase. J Psych Res. 2004; 38:365-370.
  2. Ganji V et al. Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey. Int Arch Med. 2010; 3:29.
  3. Beydoun MA et al. Serum folate, vitamin B-12 and homocysteine and their association with depressive symptoms among US adults. Psychosom Med. 2010; 72:862-873.
  4. Gilbody S et al. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidem. 2007; 165:1-13.
  5. Samer CF et al. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013; 17:165-184.

Bone Health

  1. Estrada K et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012; 44(5):491–501.
  2. Koller DL et al. Meta-analysis of genome-wide studies identifies WNT16 and ESR1 snps associated with bone mineral density in premenopausal women.  J Bone Miner Res. 2013; 28(3):547–558.
  3. Haussler CA et al. Molecular Mechanisms of Vitamin D Action. Calcified Tissue International 2013; 92:77-98
  4. Kim JH et al. Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskel Dis. 2014; 5(1):13–31.
  5. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville (MD): Office of the Surgeon General (US): 2004.

Cardiac Health

  1. Wilson PWF.  Overview of the risk equivalents and established risk factors for cardiovascular disease.
  2. Munir M et al. The association of 9p21-3 locus with coronary atherosclerosis: a systematic review and meta-analysis. Medical Genetics. 2014; 15:1-10.
  3. Karvanen J et al. The Impact of Newly Identified Loci on Coronary Heart Disease, Stroke and total Mortality in the MORGAM Prospective Cohorts. Genetic Epidemiology. 2009; 33:237-246.
  4. Zende PD et al. Apolipoprotein E Gene Polymorphism and Its Effect on Plasma Lipids in Arteriosclerosis. Journal of Clinical and Diagnostic Research. 2013; 7:2149-2152.
  5. Kotze MJ & SJ van Rensburg. Pathology supports genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer’s disease. Metabolic Brain Disease. 2012; 27:255-266.
  6. Szabo GV. The role and importance of gene polymorphisms in the development of atherosclerosis. Interventional Medicine & Applied Science. 2013; 5(1):46-51.
  7. Goracy I et al. C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in Polish subjects. J Appl Genet. 2009;50(1):63–7.
  8. Daly A. Pharmacogenetics of adverse drug reactions. Genome Medicine. 2013; 5 (5):1-12
  9. Gharani N et al. The Coriell personalized medicine collaborative pharmacogenomics appraisal, evidence scoring and interpretation system. Genome Medicine. 2013; 5 (93):1-19.
  10. Mendis S et al. World Health Organization; 2011. Global atlas on cardiovascular disease prevention and control.

Nutritional Health

  1. Borel P et al. Genetic Variations Involved in Interindividual Variability in Carotenoid Status. Mol Nutr and Food Res. 2012; 56(2):228-40.
  2. Benyamin B et al. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat Genet. 2009; 41:1173-1175
  3. Malik S et al. Common variants of the vitamin D binding protein gene and adverse health outcomes Crit Rev Clin Lab Sci, 2013; 50(1):1–22.
  4. Tanaka T et al. Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations. Am. J. Hum. Genet., 2009; 84:477–482.
  5. Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–3.

Pain Management

  1. Janicki P. Pharmacogenomics of Pain Management in T.R. Deer et al. (eds.) Comprehensive treatment of chronic pain by medical, interventional, and integrative approaches. 2013; 23-33.
  2. Marucci C et al, Unrecognized drug-drug interactions; a cause of intraoperative cardiac arrest? Anesth Analg. 2006; 102(5):1569-1572.
  3. Phillips KA et al. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001; 286(18):2270-2279.
  4. Ingelman-Sunberg M: Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci 2004; 25:193-200.
  5. Galley HF et al. Pharmacogenetics and anesthesiologists. Pharmacogenomics 2005; 6:849-856.
  6. Fagerlund TH and O Braaten. No pain relief from codeine? An introduction to pharmacogenetics. Acta Anaesthesiol Scand 2001; 45:140-149.

Weight Management

  1. Loos RJF et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genetics. 2008;40:768-775.
  2. Frayling TM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007; 316: 889–894.
  3. Masuo K et al. Relationships of Adrenoreceptor Polymorphisms with Obesity. Journal of Obesity. 2011.
  4. Bauer F et al. Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. American Journal of Clinical Nutrition. 2009; 90: 951-959.
  5. Baier LJ et al. An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance. J Clin Invest.1995;95:1281-1287.
  6. Jaaskelainen A et al. Meal Frequencies Modify the Effect of Common Genetic Variants on Body Mass Index in Adolescents of the Northern Finland Bith Cohort 1986. PLOS One. 2013; 8:9: e73802.
  7. Contact Us for a More Extensive Reference List


  1. Frosst P  et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–3.
  2. Van der Put NM et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998; 62(5):1044–51.
  3. Weisberg I et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64:169–72.

Celiac – DQ2/DQ8

  1. Megiorni F et al. HLA-DQ and risk gradient for celiac disease. Hum Imm. 2009; 70:55-59.
  2. Megiorni F et al. HLA-DQA1 and HLA-DQB1 in celiac disease predisposition: practical implications of the HLA molecular typing. J of Biomed Sci. 2012; 19:88.
  3. Abadie et al. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu. Rev. Immunol. 2011; 29:493-525.
  4. Kagnoff MF. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest. 2007; 117:41-49.
  5. Megiorni F et al. HLA-DQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects. Am J Gastroenterol. 2008; 103:997-1003.
  6. Karell et al. HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02(DQ2) heterodimer: results from the European genetics cluster of celiac disease. Hum Immunol. 2003; 64:469-477

A Leptin Resistance Solution?

Leptin is a hormone that signals the very important message, “I am not hungry”. In a culture that has easy access to tempting foods, why would anyone ever want to stop eating? The answer to this question lies in the body’s ability to feel full. Leptin is produced primarily by adipose tissue and, when the systems works the way it should, the body increases leptin levels which triggers a decrease in appetite1. At first glance this may seem like a perfect system, but just as with insulin, when the levels of leptin are high for an extended period of time, resistance to the signal develops 2. The consequence of this is called leptin resistance and it leads to an increased feeling of hunger, decreased feelings of satiety, and more eating action resulting in weight gain. This is an important survival mechanism when there is only seasonal supply of food, and when it is important to build up energy stores to be burned when less food is available. However, in modern times, when food is available all year round, leptin resistance increases the risk of a patient becoming obese.

As incidence of leptin resistance is increasing in the obese population, providers are looking for ways to improve the leptin signaling process and decrease resistance. Since leptin is a key link between nutrition and many physiologic systems, understanding leptin resistance, and possibly finding a way to intervene between insulin and leptin signaling, has become a major goal3,4. Any diet which is high in sugar, particularly fructose,5 leads to excess insulin being secreted by the body 6. Chronically elevated insulin levels help to block leptin’s negative feedback signal.The moral of the story here is to significantly reduce carbohydrate, especially refined, simple carbohydrate.

Genetics can also play an important role in the way the hypothalamus processes the signal leptin. Research established a gene called SH2B1 which encodes for a protein that is a positive regulator of both insulin and leptin action8. Deletion of the SH2B1 gene entirely can very easily lead to severe obesity, insulin resistance, and leptin resistance8. Some people possess a single nucleotide polymorphism (SNP) in SH2B1 called rs7498665 which has been associated with an alteration to the protein product. The SNP rs7498665 has also been strongly correlated to an increased BMI in people who possess the variant.9 Because leptin resistance is associated with receptor signaling in the hypothalamus, researchers are starting to look at the connection between this SNP in the gene SH2B1 and obesity. Understanding the influence genes have on patient presentation can help the practitioner to focus their treatment. When treating patients with the SNP rs7498665 it is important to optimize the body’s response to leptin.

As leptin resistance is better understood, treatment of this condition is becoming more important to clinicians. Some research shows that a long-term exercise strategy can be a valuable tool for gradually decreasing leptin resistance by reducing both insulin and leptin levels; however changing diet away from simple carbohydrates and saturated fats and portion control can have the greatest long term effect. Genetic testing can be a valuable tool for identifying patients that maybe at risk for leptin resistance, and can help the practitioner target their treatment protocol to each specific patient.


  1. Kam, Katherine. Reviewed by Martin, Laura MD (01/2010). WebMD. The Facts on Leptin: FAQ.
  2. Munzberg Heike, Flier Jeffrey, Bjorbaek, Christian. “Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice”. Endocrinology 145 (11) (2004) 4880-4889.
  3. Ozcan L, Ergin AS, Lu A, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9(1):35-51.
  4. Mancour LV, Daghestani HN, Dutta S, et al. Ligand-induced architecture of the leptin receptor signaling complex. Mol Cell. 2012;48(4):655-61.
  5. Merat S, Casanada F, Sutphin M, Palinski W, Reaven PD. Western-type diets induce insulin resistance and hyperinsulinemia in LDL receptor-deficient mice but do not increase aortic atherosclerosis compared with normoinsulinemic mice in which similar plasma cholesterol levels are achieved by a fructose-rich diet. Arterioscler Thromb Vasc Biol. 1999;19(5):1223-30.
  6. Aijälä M, Malo E, Ukkola O, et al. Long-term fructose feeding changes the expression of leptin receptors and autophagy genes in the adipose tissue and liver of male rats: a possible link to elevated triglycerides. Genes Nutr. 2013;8(6):623-35.
  7. Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front Neurosci. 2013;7:51.
  8. Maures Tj. Et al. SH2B1 (SH2-B) and JAK2: a muiltifunctional adaptor protein and kinase made for each other. Trends Endocrinol Metab. 2007; 18: 38-45.
  9. WillerCj et al. Six new loci associated with body mass index highlight a neuronal influence on bodyweight regulation. Nature Genetics. 2009:25-34.

Leptin resistance genetics

MC4RGene – the Obesity Link

The escalating population prevalence of obesity and its serious implications for public health are now generally accepted. Throughout the last twenty years, the industrialized world has transitioned from low calorie density food to high calorie density food. The ease of resource distribution, the invention of trans-fats which prolonged shelf life of food, the recent unlimited availability of low-cost calorie-dense food, along with increasing sedentary lifestyle, has played a major role in the adult obesity pandemic.

The major driving force behind obesity in modern society is overeating, which is largely coded in genes that are responsible for appetite and satiety regulation. Appetite is the desire to eat, while satiety refers to the sensation of fullness after eating. The Melanocortin4 Receptor (MC4R) refers to a gene found on chromosome 18 and the receptor that this gene creates. The MC4R is located in the hypothalamus, a region of the brain responsible for appetite (among other functions). Mutations in and near the MC4R gene account for up to 6% of severe early-onset obesity cases, suggesting an important role for the central melanocortin system in the maintenance of normal body weight. MCR4 variant has been linked to obesity, diminished insulin response in the brain, altered eating behaviors, and is believed to impair MC4R function.

The MC4R allele results in a tendency for increased appetite and a preference for calorie-dense foods. However, studies in children and teens show that even though carriers of the high risk variant near MC4R are more prone to weight gain, homozygous variant carriers may be even more responsive than non-carriers or heterozygotes to lifestyle modifications. The most effective weight loss strategy for the MC4R variant carriers is calorie restriction through portion control and smart food choice.

The MC4R Variant – Diet and Lifestyle Tips

  • Limit fat in the diet. High fat diets stimulate overeating even after returning to a normal fat diet. Low fat diets reduce the risk of overeating. The ideal allocation of calories is approximately 45% Carbohydrates, 35% Protein, 20% Fat.
  • Control carbohydrate intake and focus on eating low starch carbohydrates such as cruciferous vegetables, fruit with skins, root vegetables with low sugar content such as carrots and rutabagas.
  • Eat a high fiber diet to maintain that feeling of being full for a longer period of time.
  • Eat 5+ small meals a day. MC4R genotype can have an increase tendency to snack so it is better to plan for these tendencies and spread out calories over many small meals.
  • Exercise daily. 50 minutes daily at 65-75% maximum heart rate reduces the influence of the allele. 50-60 minutes may be too large of a time frame for some people to set aside to exercise. It is okay to break this amount into 2-6 smaller intervals over the course of the day but it is important to get the full 50-60 minutes into the daily schedule. Research has shown that there is some benefit to smaller intervals of exercise more frequently in the day, but the most important thing is that the body moves for at least an hour a day to best reduce the effects of the MC4R variant on weight loss efforts.

Coconut oil the Super Food

Is it Right for Everyone?

Most people who think about healthy foods think about coconut oil. With the surge of interest you can now find it in every store. But the question most people should be asking is if it is right for everyone. FABP2 is a gene that is involved in fat absorption through the digestive tract by encoding for a protein that is crucial for the effective binding of fatty acids2. Some people have an allele that causes them to absorb certain types of fatty acids more easily, this variant is called Ala54Thr2,3,4. These people have a change in the common gene that causes an amino acid conversation to take place in the fatty acid binding protein there by increasing its binding affinity for both long chain saturated fats and unsaturated fatty acids by two-fold2,3,4. It is no surprise that a person with this genetic variation might struggle with maintaining a healthy BMI.

In the past, all foods containing saturated fatty acids were thought to be unhealthy, however research concerning coconut oil has shown that not all these fats contribute to disease. Research has shown that coconut oil contains mostly medium chain triglycerides (MCT) that are formed from fatty acids of chain length 8:0 to 14:05. MCT have been shown in research studies to decrease fat deposits in comparison to consumption of other fats. Because coconut oil contains mostly medium chain triglycerides, its absorption rate is not affected by the variant FABP2.


  1. LIU Zhongchen CHEN Daiwen* YU Bing LV Mei MAO Xiangbing HAN Guoquan CHEN Hong MAO Qian(Key. Effects of Different Fat Sources on Growth Performance and Lipid Metabolism in Weened Piglets., 2011-09.
  2. Baier Lj et al. An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding increased fat acid binding, increased fat oxidation, and insulin resistance. J Clin Invest.1995;95:1281-1287.
  3. Almeida JC et al. The Ala54Thr polymorphism of the FABP2 gene influences the postprandial fatty acids in patients with type 2 diabetes. J Cin Endocrin Met. 2010;95:3909-3917.
  4. Levy E et al. The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants. J Biol Chem. 2001;276:39679-39684.
  5. Pehowich DJ., Gomes AV., Barnes JA., Fatty acid composition and possible health benefits of coconut oil. The West Indian Medical Journal (2000). 49(2):128-133.

Heart Health, Brain Health and Apolipoprotein E.

The heart and the brain may seem separate at first glance, but doctors know everything is connected. Heart and brain health are important to help patients to both survive, and thrive. One of the key players in the health of these two systems is a protein by the name of Apolipoprotein E (ApoE). ApoE is an important lipid transporting protein whose job is to carry cholesterol from the blood into the cell; it is the principle cholesterol carrier of the brain.1 The gene that encodes for ApoE can produce three different isoforms of the protein depending of which allele is carried. These different isoforms can affect the body differently causing either an increase or decrease in both cardiovascular health as well as plaque formation in the brain.2 So what are the three isoforms of ApoE and how do they affect patients?

The three isoforms: ApoE2, ApoE3, and ApoE42 have different effects on the body. Of the three, ApoE3 is considered the wild type; it neither increases nor decreases the chance of developing cardiovascular disease or Alzheimer’s disease.2 People with this isoform transport cholesterol into cells at a normal rate. However people with the isoform E4 have difficulty with cholesterol transportation which causes a buildup of cholesterol in the vascular system which leads to atherosclerosis.3 Another way in which the Apoe4 isoform can affect the body is by reduced break down of peptide beta amyloid plaques (Aβ) which are seen to be high in patients with Alzheimer’s disease.4-6 Lastly the isoform E2 actually conveys a decreased chance of developing cardiovascular disease and has been shown to increase the breakdown of Aβ plaques in the neural tissue causing a protective effect to the brain.7 However in less than 2% of people with the E2/E2 genotype a condition can develop called type III hyperlipoproteinemia which is characterized by high levels of total cholesterol, LDL and triglycerides. People who have two copies of the E2/E2 allele will benefit greatly from routine lab work checking their cholesterol and triglyceride levels.2,7

Apolipoprotein E may seem like one tiny little player in the lipid transport pathway, but its variation in isoforms can have serious effects on a patient. Prior knowledge of a person’s genotype can be a huge advantage to managing their care. When a patient presents with a family history of either Alzheimer’s Disease or Cardiovascular Disease, it is worth testing the gene to understand the particular risk that patient is facing. Information confers power, knowing the risk can help both you and the patient take proactive steps to maintain health for as long as possible.


  1. Puglielli L, Tanzi RE, Kovacs DM (April 2003). “Alzheimer’s disease: the cholesterol connection”. Nature Neuroscience. 6 (4): 345–51. doi:10.1038/nn0403-345. PMID 12658281.
  2. Weisgrabert K., InnerarityT., Mahley R. Abnormal Lipoprotein Receptor-binding Activity of the Human E Apoprotein due to Cysteine-Arginine Interchange at a Single Site. March 10, 1982 Journal of Biological Chemistry. Vol 257. Pp. 2518-2521
  3. Mahley, Robert, Rall SC Apolipoprotein E:far more than a lipid transport protein. Annual Rev Genomics Hum Genet. 200; 1:507-37.
  4. Liu CCI, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013 Feb 9 (2):106-18. Doi: 10.1038/nrneurol. 2012.263.
  5. Liu Y1, Yu JT2, Wang HF3, Han PR4, Tan CC5, Wang C5, Meng XF5, Risacher SL6, Saykin Aj6, Tan L2. APOE genotype and neuroimaging markers of
  6. Alzheimer’s disease: systematic review and meta-analysis. Neurol Neurosurg Psychiatry. 2015 Feb;86(2):127-34. Doi: 10.1136/jnnp-2014-307719.
  7. Haung Wl, Qiu C, von Strauss E, Winblad B, Fratiglioni L. APOE genotype, family history of dementia, and Alzheimer’s disease risk: a 6-year follow-up study. Arch Neurol. 2004 Dec; 61 (12):1930-4.
  8. Mahley, Robert, Hauang, Yadong, Rall C. Stanley Jr. Pathogenesis of type III hyperlipoproteinemia (dsybetalipoporteinemia): questions, quandaries and paradoxes. Journal of Lipid Research. 1999. 40:1933-1949.


Pharmacogenetic References

Pain Management PGx

  1. Janicki PK. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches. Deer TR et al. eds. 2013.
  2. Phillips KA et al. Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions. JAMA. 2001; 286(18):2270.
  3. Xu Y and Johnson A. Opioid therapy pharmacogenomics for noncancer pain: efficacy, adverse events, and costs. Pain Res Treat. 2013; 2013:943014.
  4. U.S. Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling. 08/18/2014. Available at:
  5. Trescot AM and Faynboym S. A Review of the Role of Genetic Testing in Pain Medicine. Pain Physician. 2014; 17:425-445.
  6. Samer CF et al. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013; 17(3):165-84.
  7. Jannetto PJ and Bratanow NC. Pharmacogenomic considerations in the opioid management of pain. Genome Med. 2010; 2:66.
  8. Hicks JK et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther. 2013; 93(5):402-8.
  9. Lamba J et al. PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenet Genomics 2012; 22(7):555-8.
  10. Sadhasivam S and Chidambaran V. Pharmacogenomics of opioids and perioperative pain management. Pharmacogenomics. 2012; 13(15):1719-40.

Psychotropic- PGx

  1. Bloom D et al. The Global Economic Burden of Non-Communicable Diseases. Geneva: World Economic Forum. 2011:1-48.
  2. Zandi PP and Judy JT. The Promise and Reality of Pharmacogenetics in Psychiatry. Psychiatr Clin North Am. 2010;33(1):181-224.
  3. Rush AJ et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. 2006; 163:1905-1917.
  4. Kelly K et al. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-18.
  5. Haddad PM et al. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Relat Outcome Meas. 2014; 5:43-62.
  6. Velligan DI et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry. 2009; 70 Suppl 4:1-46; quiz 47-8.
  7. U.S. Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling. 08/18/2014. Available at:
  8. Hicks JK et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther. 2013; 93(5):402-8.
  9. Samer CF et al. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013; 17(3):165-84.

Cardiac PGx

  1. Ganesh SK et al. Genetics and genomics for the prevention and treatment of cardiovascular disease: update: a scientific statement from the American Heart Association. Circulation. 2013; 128(25):2813-51.
  2. Samer CF et al. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013; 17(3):165-84.
  3. Sim SC et al. Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects. Pharmacogenomics J. 2013; 13(1):1-11.
  4. Kitzmiller JP et al. Pharmacogenomic testing: relevance in medical practice: why drugs work in some patients but not in others. Cleve Clin J Med. 2011; 78(4):243-57.
  5. Van Driest SL et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin Pharmacol Ther. 2014; 95(4):423-31.
  6. Johnson JA et al. Institutional profile: University of Florida and Shands Hospital Personalized Medicine Program: clinical implementation of pharmacogenetics. Pharmacogenomics. 2013; 14(7):723-6.
  7. Tomaszewski M et al. Statin-induced myopathies. Pharmacol Rep. 2011; 63(4):859-866.
  8. Link E et al. SLCO1B1 variants and statin-induced myopathy–a genomewide study. N Engl J Med. 2008; 359(8):789-99.
  9. Ramsey LB et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014; 96(4):423-8.
  10. Johnson J et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011; 90(4):625-9.
  11. Scott S et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther. 2011; 90(2):328-332.
  12. Voora D and Ginsburg GS. Clinical application of cardiovascular pharmacogenetics. J Am Coll Cardiol. 2012; 60(1):9-20.
  13. Varga E and Moll S. Prothrombin 20210 mutation (factor II mutation). Circulation. 2004; 110:e15-8.
  14. Shaheen K et al. Factor V Leiden: how great is the risk of venous thromboembolism? Cleve Clin J Med. 2012; 79(4):265-72.
  15. McNulty H et al. Homocysteine, B-vitamins and CVD. Proc Nutr Soc. 2008; 67(2):232-7.
  16. Miranda-Massari JR et al. Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control. Curr Clin Pharmacol. 2011; 6(4):260-273.
  17. Refsum H et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with disease. J Nutr. 2006; 136:1731S-1740S.
  18. Kitzmiller JP et al. Statin pharmacogenomics: pursuing biomarkers for predicting clinical outcomes. Discov Med. 2013; 16(86):45-51.

Weight Management

Weight Management is a challenge for many patients.  The extra pounds contribute to a myriad of health issues and can also result in a destructive cycle of shame and self-blame which impedes the healing process further.With an array of potential diet plans now available, it can be a challenge to know which approach to recommend for each individual patient.  The Kashi Weight Management Panel takes the guesswork out of determining the right plan by going straight to genetics for the answers. Our test provides analysis of genes highly associated with weight gain and elevated body mass index (BMI). Using your results, we offer dietary and lifestyle recommendations that are scientifically supported to help get the fastest results without all the trial-and-error of dieting. For many, a personalized strategy tailored to their genetic code can make a significant impact.

Genetic Markers Included in the Weight Management Panel

FTO Appetite Regulation, Calorie Intake, Frequent Cravings
MC4R Appetite Regulation, Carbohydrate Digestion, Metabolism Regulation, Insulin Regulation
FABP2 Dietary Fat Sources, Fat Utilization, Metabolism Regulation, Insulin Regulation
ADRB2 Physical Activity, Carbohydrate Digestion, Insulin Regulation
SH2B1 Leptin Production, Carbohydrate Cravings, Insulin Regulation

Ideal Candidates are Patients with the Following Symptoms or Conditions

  • Poor Results From Prior Dietary Changes
  • Frequent Cravings and Over-eating
  • Sedentary Lifestyle
  • Persistent Weight Gain
  • High BMI (>25)
  • Weight Gain In The Stomach, Hips And Thighs

VA Using Ketamine for PTSD and Depression | IV Ketamine for Depression | 703-844-0184 | Alexandria, Va | 22306 | Ketamine therapy | IV Ketamine center | Ketamine doctor | Springfield, Va | Fairfax, Va 22314 22304

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia

CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.  << Email for questions to the doctor

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Ketamine Virginia = Ketamine IV Drip Doctors

The IV Medical Center - IV Vitamin Drips for wellness and recovery


The VA Recognizes Ketamine As An Emergency Treatment For PTSD And Depression Patients At High Suicide Risk

CLEARWATER, Fla., Sept. 27, 2018 /PRNewswire/ — Long used as an safe and effective sedative for surgery, Ketamine has found new life as a treatment for severe depression, PTSD and suicidal ideation. Praised by some mental health experts, the drug so far has achieved very good results in clinical trials. The military now recognizes its’ potential, and last fall Brooke Army Medical Center in San Antonio became part of study on its effects. BAMC will treat active-duty troops with Ketamine, while a VA hospital near Yale will treat veterans. Another study is currently underway at a Veterans Affairs medical center in Cleveland, Ohio. The VA is trying to stem the tide of rising suicide rates among veterans, which average 22 per day – that’s one suicide every 65 minutes.

A staff psychiatrist at the Louis Stokes Cleveland VA Medical Center in Ohio, Dr. Punit Vaidya stated “30% of individuals with major depression don’t respond to traditional medications, so people can become desperate for things that work, because they can have a huge impact on their quality of life, and their overall functioning. The effects of the ketamine infusion can often be seen within a day, if not hours,” Vaidya explained. “If you look at their depression ratings and suicidal ratings given right before treatment and even four hours later you can see a significant reduction and I think that’s really quite remarkable,” Vaidya said.

Dr. Ashraf Hanna, a board certified physician and director of pain management at the Florida Spine Institute in Clearwater, Florida discusses PTSD and Treatment-Resistant Depression: “There are many forms of depression that can be treated by a psychiatrist with various modalities, anti-depressants and psychotherapy. IV Ketamine therapy is only reserved for those patients that have Treatment-Resistant Depression that have failed conventional therapy. IV Ketamine infusion therapyhas offered a new hope to patients that had no hope.”

When asked what prompted his use of IV Ketamine for PTSD and Depression and if any universities were involved in its development, Dr. Hanna went on to say: “There have been multiple universities involved in the research such as Harvard, Yale and Stanford that have proven the success rate of IV Ketamine for treatment-resistant depression. Since I was already successfully using IV Ketamine for CRPS/RSD,FibromyalgiaNeuropathy, and Post-Treatment Lyme Disease Syndrome, with over 10,000 infusions to date, I wanted to expand the treatment for PTSD, Depression, bipolar and Obsessive Compulsive Disorders. Since I am not a psychiatrist, I do not treat depression, but I work with qualified psychiatrists, and if he or she feels the patient has failed other treatment modalities, I then administer IV Ketamine for treatment-resistant depression.”

Dr. Bal Nandra and Ketamine patient Jason LaHood on how Ketamine is redefining the way patients are treated for depression



Links for Ketamine Articles

  1. – What It’s Like to Have Your Severe Depression Treated With a Hallucinogenic Drug
  2. Huffington Post – How Ketamine May Help Treat Severe Depression
  3. Murrough, Iosifescu, Chang et al. Antidepressant Efficacy in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial  Am J Psychiatry. 2013 Oct 1, 170(10): 1134-1142
  4. Murrough, Perez, Pillemer, et al.. Rapid and Longer0Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression Biol Psychiatry 2013 Aug 15; 74(4): 250-256
  5. Murrough, Burdick, Levitch et al. Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial Neuropsychopharmacology 2015 Apr; 40(5): 1084-1090
  6. Feder, Parides, et al. Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder A Randomized Clinical Trial Jama Psychiatry 2014 June;71(6): 681-8
  7. Schwartz, Murrough, Iosifescu Ketamine for treatment-resistant depression: recent developments and clinical applications Evid Based Ment Health 2016 May; 19(2):35-8
  8. Rodriguez, Kegeles, et al Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept Neuropsychopharmacology 2013 Nov; 38(12): 2475-2483
  9. Singh, Fedgchin, Daly et al. A Double-Blind, Randomized, Pacebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry 2016 August; 173(8): 816-826
  10. Taylor,  Landeros-Weisenberger, Coughlin et al. Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial  Neuropsychopharmacology 2017 August;



We will ask you to fast for 8 hours before your infusion. Once you have checked in, you will complete a questionnaire to assess your current status. The IV will be started in your hand or your arm using a small catheter. This may feel like a sting from a small bug bite. The Ketamine will be administered through your IV over a period of 40 minutes. We will take your vital signs before, during, and after the infusion. After resting for an additional 15-20 minutes after the infusion, you will be discharged home with your driver.

  1. What is Ketamine? 
    Ketamine is an anesthetic drug that has been available since the 1960’s. In high doses, it can cause a ‘dissociative anesthesia” which induces hypnosis like states as well as unconsciousness. Around 2000, scientists started looking at Ketamine IV infusions carefully when its clinical usefulness was expanded to include a role in the management of mood disorders as well as chronic pain.
  2. Why can I not drive the day of the infusion?
    Ketamine is a potent anesthetic. As with any anesthetic, we advise our patients to NOT operate any heavy machinery for the remainder of the day due to potential residual effects.
  3. What are the side effects?
    Less than 2% of people will experience side effects. Some of the common side effects are: drowsiness, nausea, dizziness, poor coordination, blurred vision, and feeling strange or unreal. Most of these symptoms dissipate after the first hour of receiving the infusion.
  4. Are there certain conditions that are contra-indications for Ketamine treatment?
    Yes. If you have a history of cardiovascular disease, uncontrolled hypertension, history of psychosis, history of failed Ketamine infusion treatment, history of substance abuse or dependence within the year (patients will undergo a screening process) you will not qualify for Ketamine infusion treatments.
  5. How will I know if I need a booster infusion and how frequently will I require them?
    The duration of antidepressant efficacy after the initial treatment is different for everyone. The studies show that the variance can be 15 days to indefinitely. This is quite a range and unfortunately, there are no predictors for the duration.
  6. Is there a guarantee that this will work for me?
    Unfortunately, we cannot give guarantees.  Studies have shown that 70% of people will obtain efficacy.  After the first 2 infusions, we will be able to ascertain whether the infusions will work for you. We will not advise you to continue your treatment after the first 2 infusions if we do not see a certain amount of improvement.
  7. Isn’t Ketamine addictive? 
    Ketamine has the potential to be addictive. Studies have shown that at these doses and frequency, Ketamine is not addictive.
  8. Do I have to continue my current treatments for depression? 
    Yes. We advise that you alert your current health care provider that you are undergoing these treatments and that you maintain your current regimen.  It can be dangerous to stop taking your medications without the care of a physician. Our patients have a brighter outlook and a positive drive after their treatment that has allowed them to have higher success rates with psychotherapy. We will be happy to work with your current health care provider to provide the optimal outcome.


CBD Allergies | CBD Medical Use| 703-844-0184 | Fairfax, Va 22306


CBD and allergies | CBD and Health | Addiction Domain Link 

The link above is the start for this stream of consciousness:


A Guide to cannabis allergies:

A Growing Need for Information About Cannabis Allergies

Nobody likes allergies, right? In fact, everyone I know absolutely despises them. According to the American College of Asthma, Allergy, and Immunology, more than 50 million Americans suffer from allergies each year. Cumulatively, that’s a huge number of people who will experience some sort of allergic reaction at a point in their life, whether it be to a particular variety of food, pollen, mold, or perhaps a more specific irritant such as cats.

What if, however, you found yourself with an allergic reaction to your job, or to something you greatly enjoyed, or, even worse, to something that you need? Stories of cannabis allergies have been emerging at a growing rate since legalization and reveal that they can frequently strike down budtenders, recreational consumers, and medical patients with a variety of symptoms.

Can Cannabis Users Donate Blood?

For example, here is one of the typical communications we receive on the topic:

“I have tried one medical marijuana, and I used it for about 12 days. I found I was allergic to it. Then just to verify it was the hemp, I smoked a little, and got the same reaction. Bad allergies, total constant nasal drip, watery eyes, stuffy head. My eyes would even burn at times. Is there something equivalent for pain, that will not give me such bad effects? Or is there somewhere I can investigate further? I think it really does some of my arthritic pain. Thank You.” – Anonymous

Given the increasing frequency of these stories about people being allergic to cannabis, and the apparent need for more information, we felt it necessary to investigate the matter further.

An Unusual Background: Cannabis Allergy Research

Allergy research

After scooting beneath the radar of the scientific community for the longest time, marijuana allergies appear to be on the rise. Just as cannabis consumption has been trickling towards the mainstream in the U.S., cannabis allergies have been attracting increased attention from researchers. The correlation between the rise in allergies and the increase in legalization initiatives is surely significant.

From the outset, we should outline a number of quixotic attributes specific to cannabis and its production that make it particularly interesting as a source of allergies. First off, similar to plants such as ragweed, cannabis pollen grains are very buoyant, allowing for distribution across many miles, which can increase their effectiveness as an irritant. Though typically only produced by male plants, pollen can also be produced by females that express hermaphroditic male flowers. That there are a variety of preparations of cannabis sativa adds another level of complexity.

Cannabis Anatomy: the Parts of the Plant

As you might be well aware, there are a multitude of ways in which cannabis products can be consumed. They can be smoked, vaporizedchewed, taken as a tincture, or used as a topical lotion. In addition to these factors, the isolation of female flowering plants, which aims to prevent pollination, increases the plant’s psychoactive properties by raising its THC content. As a result, the potency of cannabis has increased drastically over the years. Tragically, this could also play a role in allergic disease because THC has been suggested as a potential cannabis allergen.

Can You Really be Allergic to Cannabis?

Box of tissues

Allergies are an immune overreaction by the body attempting to protect the respiratory system from outside invaders. The antibodies produced by the body succeed in keeping the perceived foreign invaders out, but also cause the symptoms characteristic of allergic responses. Pollen, the most common allergen, is a powder released by trees, grasses, and weeds to fertilize the seeds of neighboring plants. Mold, somewhat differently, is a spore that grows on rotting logs, dead leaves, and grasses. While dry-weather mold species exist, many types of mold thrive in moist conditions.

Root Rot, Mildew, and Leaf Septoria: How to Deal with These 3 Cannabis Plant Diseases

Perhaps not so shockingly, given that both these allergens are associated with cannabis, researchers in Belgium recently published an article entitled “Emerging allergens: Cannabis.” The researchers focused in particular on cannabis sativa, one of the two species we all know colloquially as marijuana. They found that the plant can cause a number of allergic symptoms such as allergic rhinitis (hay fever), conjunctivitis (pink eye), skin rashes, and asthmatic symptoms when smoked, inhaled, or chewed. Yikes! On reading that our interest was piqued. This is a thing; an actual thing!

What are Cannabis Allergies and Their Symptoms?

Asthma inhaler with spirometry test results

Before getting too far ahead of ourselves, it’s important to differentiate between legitimate cannabis allergy symptoms and allergic reactions to substances found in cannabis that are actually not inherent to the plant, such as molds. Put simply, cannabis can become moldy when stored and people with mold allergies may have reactions. Some people could even experience reactions to both the plant and mold.

It’s a tad confusing, but we do have proof. The presence of fungal contamination in marijuana samples has been demonstrated, occasionally being capable of putting patients with sub-par immune systems at risk for invasive disease. A case of allergic bronchopulmonary aspergillosis attributed to the fungal contamination of a patient’s marijuana supply has even been described. Doesn’t sound good, right? It took a course of steroids to remedy the situation.

How Long is My Cannabis Good For? Leafly's Guide to Storing Cannabis

To be pedantic, a true cannabis allergy is a reaction to a specific substance contained within the cannabis plant. In “Cannabis Sativa: the unconventional ‘weed’ allergen”, Ocampo and Rans provide an excellent review of the existing literature on the subject. They outline how reports in the medical literature have described episodes of allergic reactions, hypersensitivity, and even anaphylaxis to cannabis in its various forms.

Cannabis pollen inhalation has been noted to cause symptoms of allergic rhinitis, conjunctivitis, and asthma. Pollen or smoke exposure has resulted in nasal congestion, rhinitis, sneezing, conjunctival injection, pharyngeal pruritus (itchy throat), coughing, wheezing, and dyspnea (difficulty breathing).

Cases of skin irritations thought to be associated with cannabis consumption have been described. Skin contact through the handling of plants has been associated with urticarial (hives), generalized pruritus (itching), and periorbital angioedema (swelling). Anaphylaxis (a serious reaction) associated with ocular symptoms, urticaria (hives), angioedema (swelling), dyspnea (difficult breathing), and dysphonia (difficulty in speaking) has been reported as a result of hemp seed ingestion. Allergic asthma triggered by seasonal and occupational exposure to cannabis also has been reported.

Can Cannabis Help Asthma Patients?

Cannabis consumption has even been speculated as a contributing factor in a case of eosinophilic pneumonia where the symptoms began after recreational exposure to marijuana. (And you were about to complain about those itchy eyes, you big softy!)

Varying Means of Exposure to Cannabis Allergens

Cannabis farmer

Much like other airborne substances that can trigger allergic reactions (pollen, we’re looking at you!), cannabis sensitization can be influenced by aerobiology. People who live in areas where large quantities of marijuana plants are grown may be especially prone to experiencing allergic reactions to the pollen.

In Omaha, Nebraska, where the plant reportedly grows wildly and commercially, one study looked at cannabis sensitization. This study noted that 61% of 127 patients with allergic rhino conjunctivitis and/or asthma symptoms had a positive cannabis pollen skin prick test reaction.

Rhino conjunctivitis is characterized by one or several of the following symptoms:

  • Nasal congestion
  • Runny nose
  • post-nasal drip
  • Sneezing
  • Red eyes
  • Itching of the nose or eyes
6 Smoke-Free Ways to Consume Cannabis

Seventy three percent of randomly selected patients in a cannabis-sensitive subgroup reported respiratory symptoms during the cannabis pollination season. Sensitization associated with cannabis consumption also has been suggested. Ominously, this study demonstrated a higher prevalence of skin test reaction positivity in marijuana smokers (14.6%) and even more so in those who reported frequent consumption (18.2%) compared with nonsmokers (5%).

For all the aspiring budtenders out there, allergic reactions associated with occupational exposure to cannabis sativa have been shown. A medical marijuana grower, who previously tolerated personal recreational marijuana consumption, developed skin irritations from handling plants. Two patients who did not consume cannabis noted nasal and respiratory symptoms after several years of work in a laboratory. One patient had more pronounced symptoms with handling of the sinsemilla (high-THC marijuana from the female plant), suggesting the possible allergenic role of THC in this case.

Whether in or outdoors, it seems that there might not be anywhere to hide. Not only that, but some European studies have investigated potential cross-reactivity between cannabis and other plants. Gamboa et al reported on a case of a 28-year-old cannabis smoker with progressive allergic symptoms who went on to develop urticaria to peach peel, food pollen syndrome to several foods, and anaphylaxis to tomato, pepper, and fig. Ebo et al further suggested allergic cross-reactivity to fruits, vegetables, and nuts, and even the possibility of a “cannabis–plant food syndrome.”

Identifying Cannabis Allergens

Close up of a cannabis bud

As we have seen so far, cannabis pollen has been shown to cause allergic reactions in several studies, and individuals who show sensitivity to it are usually also sensitive to pollen from other plants. However, this does not explain the cases of cannabis allergy caused by female plants with no signs of hermaphroditism. In these instances, something else must be to blame.

There have been efforts to identify specific allergens for cannabis with scientists pinpointing a number of possible culprits. A study published in 1971 suggested cannabinoids as allergens based on positive skin prick test reactions in case patients. As we’ve already mentioned, THC was specifically suggested in the case of a forensic laboratory worker handling sinsemilla variants of cannabis sativa.

More recently, a study identified a nonspecific LTP (ns-LTP) relevant to cannabis and named it Can s 3. LPTs (Lipid Transfer Proteins) are responsible for the transfer of lipids and other fatty acids across cell membranes and are often involved in food allergies. Further investigation by both Larramendi and Ebo supported the potential of Can s 3 as a major allergen in cannabis allergy.

Cannabinoids 101: What Makes Cannabis Medicine?

Additional studies have found ns-LTPs on immunoblotting, an analytical technique used to detect specific proteins. One study, aiming to define cannabis allergens, identified potential allergens including a protein called RuBisCO and a 23-kDa oxygen-evolving enhancer protein 2. Other less consistently demonstrated allergens included adenosine triphosphate synthase, phosphoglycerate kinase, glyceralderhyde-3-phosphate dehydrogenase, and luminal binding protein.

Though a lot of this terminology may seem impenetrable to the layman, the identification and characterization of cannabis allergens is crucial to the further understanding of allergic sensitization specific to this species of plant.

How is a Cannabis Allergy Diagnosis Made?

Allergy test

If you think you might have a cannabis allergy, what’s your next step? What do you do? Where do you go? Well, it’s pretty simple. You book an appointment with an allergist, of course.

The evaluation of cannabis allergies is dependent largely on skin testing. A skin prick test can detect if a person is sensitive to a specific allergen. If sensitive, to protect the body from a perceived threat, the immune system produces a type of antibody called immunoglobulin E (IgE). An allergen-specific IgE blood test is done to check whether a person is allergic to a particular substance. Because IgE antibodies are unique to each allergen, checking for specific variants in the blood can help determine if an allergy is present. The tests are not invasive and tend to produce quick results.

Cannabis Use Won’t Prevent You From Getting Insurance, But It Might Cost You

A positive skin prick test to a particular allergen does not necessarily indicate that a person will experience a reaction caused by that allergen. Therefore, healthcare practitioners must compare the skin test results with the time and place of a person’s symptoms to see if they match. If the results of prick tests are negative, they may be followed by intradermal tests, which give allergists more details about what’s causing the underlying symptoms. After either test, the area of the skin is observed for about 15 minutes to see if a reaction develops. The “wheal” (an itchy, red bump) and “flare” (surrounding redness) indicate the presence of an allergy antibody. The larger the wheal and flare, the greater the sensitivity to the allergen.

Although skin testing may seem simple, it must be carried out by trained practitioners with an understanding of the variables and risks of the testing procedure. Extracts for testing are typically created with crushed buds, leaves, and flowers of the cannabis plant. Differences in source material and extraction techniques can introduce significant variability while contaminants and additives in the native allergen can cloud diagnostic evaluation. Consequently, without reliable standardized diagnostic testing options and often poor correlation between testing and true clinical allergy, the importance of patient history in making evaluations is paramount.

Is Treatment Available for Cannabis Allergies?

Box of allergy medicine

William Silvers, a Colorado allergist, published an editorial in February 2016 discussing three recent patients with symptoms suggestive of marijuana allergies. He provides a great insight into the practical experience of an allergist dealing with potential marijuana allergies in a state where cannabis has been wholly legalized.

One patient, a frequent marijuana smoker, experienced nasal congestion that later developed into a chronic cough once he began work as a trimmer at a marijuana growth facility. Treatment with a nasal spray and inhaler helped to reduce symptoms.

Does Cannabis Make You Grumpy?

A second patient, without any prior history of asthma or allergies, demonstrated symptoms after exposure to marijuana when he began work in a grow facility and dispensary. He was diagnosed as having asthma exacerbated by marijuana exposure with hay fever, eye inflammation, and suspected contact dermatitis to marijuana. Treatment recommendations included minimizing his environmental exposure to marijuana as much as possible. The patient significantly improved with a prescribed medication program.

The final patient, a heavy marijuana consumer, was referred by an emergency department physician with suspected anaphylaxis after exposure to marijuana smoke. He admitted to smoking concentrate, a carbon dioxide extracted marijuana wax, that contained up to 60% to 70% THC levels. Puzzlingly, he showed a lack of sensitization to marijuana extracts and pollen tests were negative. The wax concentrate might have contained a contaminant or additive to which the patient reacted.

What is Cannabis Oil, Shatter, and Wax?

Despite the low, mumbled presentiments of an epidemic, in Dr. Silvers’ opinion:

…the relatively low numbers of “presentations since legalization of marijuana in Colorado suggests that cannabis sativa is a mild allergen, with significant exposure required to elicit respiratory and dermatologic allergic reactions.”

This sounds like good news for cannabis lovers and, as demonstrated, treatment is available for allergy sufferers depending on the seriousness of the reaction. Unfortunately for the chronically-allergic cannabis consumer, as with other allergens, avoidance is recommended.

Still, factors such as local aerobiology and occupational exposures need to be taken into consideration. Antihistamines, intranasal steroids, and nasal decongestants can be used to treat symptoms of allergic rhino conjunctivitis. Asthma can be treated with Beta agonists or an inhaled corticosteroid if required. EpiPens should be prescribed for patients with a history of anaphylaxis.

There have even been rare cases of treatment with immunotherapy in the literature. One report demonstrated desensitization in two patients and improvement was noted in a cohort of hemp workers who received immunotherapy extract twice a week for a year. For those experiencing symptoms, we’re not claiming that a cannabis-allergy Kryptonite has been discovered, but there are certainly a variety of options out there.

Hemp 101: What is Hemp, What's It Used for, and Why is It Illegal?


Although still relatively uncommon, allergies associated with cannabis are being reported with increased frequency. Allergic reactions as severe as anaphylaxis attributed to cannabis have been noted with sensitization associated with pollinosis, cannabis consumption, occupational exposure, and potential plant cross-reactivity. However, there is no reason to panic. It’s to be expected that the reporting of cannabis allergies would increase as cannabis consumption became more mainstream.

Cannabis allergies can be treated in much the same way as other allergies but the lack of standardization in testing limits validation and the widespread applicability of diagnostic testing. Much research is still neededto more accurately define allergens, develop a standardized extract, establish diagnostic specificity, and clarify treatment options for patients.

Without a shadow of a doubt, the legal limitations to obtaining cannabis extracts poses challenges as the only federally approved source of cannabis species in the United States is located at the University of Mississippi, while the illicit nature of cannabis consumption is still creating obstacles for patient reporting. If we’re to learn more about cannabis allergies, we need to overcome the former by enabling more wide-ranging research, while eliminating the latter by encouraging silent cannabis allergy sufferers to breach the surface of public opinion and engaging them in a non-judgmental way.      Cannabis sativa the unconventional weed allergen   << Allergists Article

Is Cannabis Addictive?

Tighter regs proposed for pesticides used on Colorado pot < Link


15 Health Benefits of Cannabis and Hemp Oil For Pain You Need to Know



Cannabis oil is widely beneficial and is considered as one of the most effective oils for alleviation of certain conditions and illnesses.

Researchers believe there are at least two active chemicals in cannabis that have medicinal applications:  cannabidiol and tetrahydrocannabinol. Cannabidiol, also known as CBD, impacts the brain without a high, and tetrahydrocannabinol, also known as THC, has pain relieving properties.

The health benefits of cannabis oil are caused by these medicinal applications. Here are the top 15 health benefits of cannabis oil:


Cannabis oil is often suggested for people who suffer from chronic pain, inflammation and occasionally in emergency pain relief. This is the reason why people who have been diagnosed with cancer turn to cannabis-related products, including cannabis oil, when they need relief from the pain of the chemotherapy or the disease itself.


The effects of cannabis oil, more specifically the cannabinoids such as THC, help to control seizures by attaching to the brain cells that are responsible for regulating relaxation and controlling excitability.


The effects of cannabis oil may be able to slow the progression of Alzheimer’s disease. THC, the active chemical in cannabis oil, slows the establishment of amyloid plaques by blocking the enzyme in the brain that makes them. Amyloid plaques are what kill brain cell and ultimately cause Alzheimer’s disease.


The elusive oils in cannabis oil can help improve heart health by balancing out the negative oils that are in a person’s system. In addition, the oil can stimulate antioxidant processes such as maximising the health of the cardiovascular system and scraping off excess cholesterol.

Eases Multiple Sclerosis Pain

One of the health effects of cannabis oil includes the ease of pain symptoms from multiple sclerosis. The THC in the cannabis oil attaches to the receptors in the nerves and muscles in order to relieve pain. There are also studies that suggest THC helps to control muscle spasms.


It’s a well-known fact that those who consume cannabis in any form notice an increased appetite. However, the use of cannabis oil can help you regulate your appetite and encourage hunger. At the same time, it can stimulate your digestive system in order to operate on a regular level.


Studies suggest one of the effects of cannabis oil could aid patients with inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. The THC and CBD chemicals interact with the body’s cells, which plays an important role in immune responses and gut functions.  The THC-like compounds that the body produce increase the permeability of the intestines, which allows bacteria in. The cannabinoids from cannabis oil block these body-made cannabinoids helping to prevent the permeability and ensuring the intestinal cells have a tightened bond.


If you suffer from the constant anxiety during the night time hours, or suffer from insomnia or struggle from getting a restful, undisturbed sleep, then cannabis oil might be the solution for you. The cannabis oil works by relaxing the mind and body, and generating a lower energy level, it will be easier for you to get your heart rate down and clear your mind to allow for a long, restful sleep.


The health benefits of cannabis oil in regards to rheumatoid arthritis include promoting sleep, reducing inflammation, and alleviating pain. These effects of cannabis oil combined help to relieve the pain and discomfort that people with arthritis have.


In regards to eye health, cannabis oil has been linked to the reduction in glaucoma and the prevention of macular degeneration. As people age, eye health is one of the major reasons why people turn to cannabis oil.


The effects of cannabis have been shown to reduce pain and tremors, and improve sleep for those who have Parkinson’s disease. There has also been research that demonstrated improved fine motor skills among its patients.


One of the most popular and well-known uses of cannabis oil is for the purpose of relief from anxiety and stress. The natural compounds found in cannabis oil are effective for releasing relaxing the mind, releasing pleasure hormone, reducing stress and inducing a sense of calmness and relaxation to the user.


The naturally occurring cannabinoids, similar to THC, contribute to the health benefits of cannabis oil. The cannabinoids help to regulate the system that causes anxiety and fear in the brain and body.  This specific use of cannabis oil has been connected to benefiting veterans with post-traumatic stress disorder.


Research shows that the effects of cannabis may help to protect the brain from the damage that is caused by a stroke. This is done by reducing the size of the area that was affected by the stroke. There has been research that has shown neuroprotective effects from cannabis that protects the brain in the case of other traumatic events, like concussions.


Early reports of research have shown that the active ingredients in cannabis oil can reduce tumour size and have preventative effects on cancer, and says that the oil makes it easier to beat cancer for those suffering with the disease


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Commonly used household cleaners could be making children overweight by altering their gut microbiota, suggests a Canadian study published in CMAJ (Canadian Medical Association Journal).

The study analyzed the gut flora of 757 infants from the general population at age 3-4 months and weight at ages 1 and 3 years, looking at exposure to disinfectants, detergents and eco-friendly products used in the home.

Researchers from across Canada looked at data from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort on microbes in infant fecal matter. They used World Health Organization growth charts for body mass index (BMI) scores.

Associations with altered gut flora in babies 3-4 months old were strongest for frequent use of household disinfectants such as multisurface cleaners, which showed lower levels of Haemophilus and Clostridium bacteria but higher levels of Lachnospiraceae. The researchers also observed an increase in Lachnospiraceae bacteria with more frequent cleaning with disinfectants. They did not find the same association with detergents or eco-friendly cleaners. Studies of piglets have found similar changes in the gut microbiome when exposed to aerosol disinfectants.

“We found that infants living in households with disinfectants being used at least weekly were twice as likely to have higher levels of the gut microbes Lachnospiraceae at age 3-4 months; when they were 3 years old, their body mass index was higher than children not exposed to heavy home use of disinfectants as an infant,” said Anita Kozyrskyj, a University of Alberta pediatrics professor, and principal investigator on the SyMBIOTA project, an investigation into how alteration of the infant gut microbiome impacts health.

Babies living in households that used eco-friendly cleaners had different microbiota and were less likely to be overweight as toddlers.

“Those infants growing up in households with heavy use of eco cleaners had much lower levels of the gut microbes Enterobacteriaceae. However, we found no evidence that these gut microbiome changes caused the reduced obesity risk,” she said.

She suggests that the use of eco-friendly products may be linked to healthier overall maternal lifestyles and eating habits, contributing in turn to the healthier gut microbiomes and weight of their infants.

“Antibacterial cleaning products have the capacity to change the environmental microbiome and alter risk for child overweight,” write the authors. “Our study provides novel information regarding the impact of these products on infant gut microbial composition and outcomes of overweight in the same population.”

A related commentary provides perspective on the interesting findings.

“There is biologic plausibility to the finding that early-life exposure to disinfectants may increase risk of childhood obesity through the alterations in bacteria within the Lachnospiraceae family,” write epidemiologists Dr. Noel Mueller and Moira Differding, Johns Hopkins Bloomberg School of Public Health, in a related commentary.

They call for further studies “to explore the intriguing possibility that use of household disinfectants might contribute to the complex causes of obesity through microbially mediated mechanisms.”

Dr. Kozyrskyj agrees and points to the need for studies that classify cleaning products by their actual ingredients. “The inability to do this was a limitation of our study.”

The research study was funded by the Canadian Institutes of Health Research (CIHR) with funding from the Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence for the CHILD study.

Original article from above – sciencedaily


Gut microbe composition different in young children with, without type 1 diabetes

Date:June 12, 2014Source:Diabetologia

Summary:Children diagnosed with type 1 diabetes have a less balanced composition of gut bacteria compared with children of the same age without diabetes, research shows. The incidence of type 1 diabetes is increasing worldwide, showing a particularly sharp increase among children under the age of 5 years. Recent studies indicate that adverse changes in gut microbiota are associated with the development of type 1 diabetes, but little is known about the microbiota in children who have diabetes at an early age.

New research published in Diabetologia (the journal of the European Association for the Study of Diabetes) shows that children diagnosed with type 1 diabetes have a less balanced composition of gut bacteria compared with children of the same age without diabetes. The research is by Dr Marcus de Goffau and Dr Hermie Harmsen, University Medical Center Groningen, the Netherlands, and colleagues.

The incidence of type 1 diabetes is increasing worldwide, showing a particularly sharp increase among children under the age of 5 years. Recent studies indicate that adverse changes in gut microbiota are associated with the development of type 1 diabetes, but little is known about the microbiota in children who have diabetes at an early age. Thus in this new study the microbiota of children aged 1 years with new-onset type 1 diabetes was compared with the microbiota of age-matched healthy controls.

A deep global analysis of the gut microbiota composition was done by phylogenetic microarray analysis using a Human Intestinal Tract Chip (HITChip), an analytical device designed specifically for studying gut bacteria.

Patients were recruited into two research projects — the DIPP (Finnish Type 1 Diabetes Prediction and Prevention) study in Finland and the international VirDiab (Viruses in Diabetes) study, which included cases and control children from seven European countries.

Faecal samples were collected from children newly diagnosed with type 1 diabetes and controls. DNA was successfully isolated from 28 diabetic children: four from France, one from Greece, three from Estonia, two from Lithuania and 18 from Finland. The diabetic children were matched with control children according to age; DNA was isolated successfully from 27 control children. One of the control children was from Lithuania and the rest were from Finland. The samples were collected from the diabetic children within 4 weeks of the diagnosis of diabetes and were coupled with samples from age-matched controls. Samples were collected by the parents at home and shipped by mail at ambient temperature to the laboratory, where they were subsequently stored at -75°C.

The researchers found that in children younger than three years, the combined abundance of the class Bacilli (notably streptococci) and the phylum Bacteroidetes were higher in diabetic children, whereas the combined abundance of the important (usually beneficial) Clostridium clusters IV and XIVa was higher in the healthy controls.

Controls aged three years and older were characterised by a higher fraction of butyrate-producing species within Clostridium clusters IV and XIVa than was seen in the corresponding diabetic children or in children from the younger age groups, while the diabetic children older than three years could be differentiated by having an unusually high microbial diversity. An increased diversity is often associated with unstable or with unusual bacterial networks; in children with coeliac disease or adults with colorectal cancer an abnormally high microbial diversity is found.*

The authors discuss that the ideal scenario for the gut is to have the right balance of bacteria to produce the fermentation product butyrate, which is readily absorbed by the human gut and turned into energy. Production of sufficient butyrate by bacteria in the gut leads to optimal gut function and prevents/minimises inflammation and other metabolic problems. The authors explain that, as the gut microbiota of very young children (1-3 years) is still developing very rapidly**, the proper kind of balance to produce butyrate is not yet exactly the same as it is when children are older than 3 years.

The authors also recalculated their results without the non-Finnish children to adjust for any geographical differences, and their main findings remained unchanged.

They say: “The results from both age groups suggest that non-diabetic children have a more balanced microbiota in which butyrate-producing species appear to hold a pivotal position. Although distinct differences have been found in each age category between the healthy and diabetic children, the main differences with regard to Clostridium clusters IV and XIVa appear to represent two sides of the same coin, as they together emphasise the importance of developing balanced bacterial cross-feeding complexes that have sufficient potential for butyrate formation.”

They add: “Dietary interventions aimed at achieving or maintaining optimal butyrate production levels might measurably reduce the risk of developing type 1 diabetes, especially in children with genetic risk for developing type 1 diabetes.”

The authors say more work needs to be done on establishing exactly what foods are best for promoting ideal gut conditions, however they conclude: “We think a diet high in fruits and vegetables is best as these are rich in fibre/complex carbohydrates, which are important because butyrate-producing species are dependent upon them indirectly via cross-feeding relations with fibre degraders. Simple sugars, on the other hand, cause an overabundance of species which are very proficient in quickly utilising sugars — Streptococci for example — thus outcompeting or limiting the amount of species which are beneficial for human health. Excessive protein and animal fat consumption might similarly indirectly negatively affect butyrate production as they stimulate non-butyrate-producing species which are very good in utilising this type of food source (such as Bacteroides).”

Story Source:

Materials provided by DiabetologiaNote: Content may be edited for style and length.

Journal Reference:

  1. Marcus de Goffau, Hermie Harmsen et al. Aberrant gut microbiota composition at the onset of type 1 diabetes in young childrenDiabetologia, June 2014 DOI: 10.1007/s00125-014-3274-0



Maintaining Your Microbiome for Health and Weight Loss

By MealEnders
July 18, 2017


Chances are, you’ve heard of probiotics: the beneficial bacteria that naturally inhabit the human gut. They’re found naturally in several food products, like yogurt, kefir, kimchi, and miso, as well as in supplement form; but they’re also popping up in processed food products like chips, juices, and snack bars. Research has shown that probiotics can boost health in a number of ways, from improving digestive health to boosting mood. And in the past few years, research has found that probiotics may also play a role in body weight and metabolism.

First, a refresher: probiotics are just one group of bacteria that make up your microbiome, the collection of microorganisms (both good and bad) that live in and on the human body. A well-balanced microbiota plays a variety of roles in the human body, including providing immune support, inhibiting the colonization of harmful pathogens, breaking down indigestible carbohydrates, synthesizing vitamins, moderating mood and cognition, and metabolism of nutrients. Alterations to the microbiome, including antibiotic use, quality and diversity of diet, exercise, and smoking, can upset this balance, leading to dysbiosis. An altered microbiome has been implicated in a number of consequences, including inflammatory bowel disease and obesity.

Several studies1,2,3 led by Peter Turnbaugh, PhD and Assistant Professor at UCSF studying the impact of the human gut microbiome on pharmacology and nutrition, have found that the microbiomes of normal weight adults versus obese adults are very different. The studies looked at two of the most prevalent families of bacteria in the gut: bacteroidetes and firmicutes. Specifically, obese individuals tend to have more firmicutes and fewer bacteroidetes than normal weight people. What’s more, when obese individuals followed low calorie diets and lost weight, their microbiome began to resemble that of a normal-weight person’s.1 Another study found that when obese individuals added a probiotic drink into their diet, they showed significant reductions in body weight, BMI, waist and hip circumference, and body fat mass.4

How exactly can probiotics regulate weight? It used to be a commonly held belief that weight loss was a matter of calories in and calories out: if you burn more calories than you eat, you’ll lose weight. But it turns out that it’s not so simple: there are factors that affect how your body metabolizes those calories that are coming in. One of those factors may be the microbiome: your gut flora may play a role in how your body extracts calories from food. For example, one strain of probiotics–Lactobacillus gasseri SBT2055–has been found to inhibit the absorption of dietary fat, thereby reducing the amount of calories your body absorbs.4,5,6 Other studies suggest that probiotics may also influence hormones, like glucagon-like peptide 1 (GLP-1). GLP-1 inhibits gastric secretion and motility, delaying the absorption of carbohydrates and thus contributing to satiety.7 In addition, obesity has been linked with inflammation–and probiotics can moderate inflammation.8 Despite these suggested mechanisms, more research is needed to explore the ways by which probiotics affect nutrient absorption.

Further complicating matters is the fact is that not all strains of probiotics are beneficial. In fact, some research implies that certain strains may promote weight gain, not loss. Certain lactobacillus strains, including L. acidophilus and L. fermentum, were associated with weight gain in both humans and animals.9L. acidophilus is a strain that is particularly prevalent in the US and is found in acidophilus milk (meant for lactose intolerant individuals) and some yogurts. And many studies fail to show any weight-reducing benefits of probiotics whatsoever.10

It’s important to remember that much of this research is new, and more studies should be done to replicate these findings. And, of course, adding probiotics to your diet isn’t the silver bullet for weight loss. If you are thinking of adding probiotics–in food or supplement form–here are our recommendations:Choose a strain with research to back it upLactobacillus gasseri is one of the most promising strains for weight loss. In one human study, adults who drank milk with L. gasserifor 12 weeks experienced reductions in weight, visceral fat, and waist and hip circumference.4 When they stopped taking the supplement, however, they gained back the weight–indicating that supplementation should be constant. L. gasseri can be found in many fermented foods, including miso, kefir, sauerkraut, and tempeh. Another product that has promising research behind it is VSL#3, a probiotic supplement made of 8 different strains. VSL#3 may actually help protect against weight gain: in a 2015 study, non-obese participants who supplemented with VSL#3 and ate a high-fat, hypercaloric diet–which required them eating 1,000 extra calories per day–gained less fat and total weight compared with those who did not take the probiotic strain.11 VSL#3 probiotic supplement is a proprietary combination of beneficial bacteria and is not found naturally in foods (although its 8 strains appear in a number of fermented foods); currently it’s available online and at certain pharmacies

Eat plenty of fiber. In order for probiotics to thrive, they need a constant supply of prebiotics, indigestible food components that act as food for and stimulate the growth of probiotics. Prebiotics are a type of fiber that remain undigested as they travel through the upper GI tract; in the lower GI tract, they are fermented by probiotics. Rich sources of prebiotics include chicory root, dandelion greens, and jerusalem artichoke, but they’re also found in more commonly eaten foods like oats, barley, bananas, asparagus, apples, leeks, onions, and garlic. If you’re already eating a diet high in vegetables, whole grains, and legumes, you’re likely already getting enough prebiotics in your diet. If you’re not, aim to increase your fiber intake to reach the recommended minimum amount of 25 and 38 grams per day for women and men, respectively. If you’re working up to this amount, start slowly–adding too much fiber at once can cause GI distress and bloating!

Limit added sugars and harmful fats. The health of your microbiome depends not only on the presence of probiotics, but also on the absence of harmful bacteria. Harmful bacteria thrive on food too: research has found that both high-fat and high-sugar diets can change the composition of the microbiome within just one day, leading to changes in microbiome gene expression and adiposity.12 Artificial sweeteners may also negatively influence the microbiome: in one study, the consumption of artificial sugars in both mice and humans increased the risk of glucose intolerance (elevated blood sugar levels that can be a precursor to diabetes), a characteristic of metabolic syndrome.13

In addition to supplements, add a wide range of probiotic-rich foods to your diet.  Beneficial bacteria found in foods and supplements frequently come from the genera Lactobacillus and Bifidobacterium. With probiotic supplements, you can select a single specific strain to add to your health regimen. Foods don’t offer that type of specificity, but typically provide more than one type of probiotic at varying levels of concentration.  For general health, a variety of probiotic-rich foods can support a healthy microbiome (plus, most probiotic-rich foods have other nutritional benefits).  In addition to yogurt, kefir, kimchi and miso, try adding tempeh, buttermilk, natto, pickles, kombucha, and sauerkraut to your diet.  Cheeses such as mozzarella, Gouda, cheddar and cottage cheese also contribute good bacteria to your system.

Augmenting your diet with probiotics could provide the extra boost you need to get the most out of a healthy, balanced diet, but it is unlikely to provide enough weight regulation power to counteract an unhealthy diet.  If you’re already eating a diet rich in fiber and plentiful fruits and vegetables, just incorporating a couple of the right probiotic-rich foods, or supplements, into your daily routine could be enough to have a positive impact on gut health, overall wellness, and, potentially, weight reduction.


  • Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006; 444(7122):1022-3.
  • Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE et al. A core gut microbiome in obese and lean twins. Nature. 2009; 457(7228):480-4.
  • Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122);1027-31.
  • Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y et al. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr. 2010; 64:636-643.
  • Ogawa A, Kobayashi T, Sakai F, Kadooka Y, Kawasaki Y. Lactobacillus gasseri SBT2055 suppresses fatty acid release through enlargement of fat emulsion size in vitro and promotes fecal fat excretion in healthy Japanese subjects. Lipids Health Dis. 2015; 14:30.
  • Hamad EM, Sato M, Uzu K, Yoshida T, Higashi S, Kawakami H et al. Milk fermented by Lactobacillus gasseri SBT2055 influences adipocyte size via inhibition of dietary fat absorption in Zucker rats. Br J Nutr. 2009;101(4):716-24.
  • Yadav H, Lee JK, Lloyd J, Walter P, Rane SG. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J Biol Chem. 2013; 288(35):25088-97.
  • Lescheid DW. Probiotics and inflammation: A review. Functional Foods in Health & Disease. 2014;4(7).
  • Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D. Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microbial pathogenesis. 2012;53(2):100-108.
  • Park S, Bae JH. Probiotics for weight loss: a systematic review and meta-analysis. Nutrition Research. 2015;35(7):566-575.
  • Osterberg KL, Boutagy NE, McMillan RP, Stevens JR, Frisard MI, Kavanaugh JW. Supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults. Obesity. 2015;23(12):2364-70.
  • Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. Effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14.
  • Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;513(181-186).



Why the Gut Microbiome Is Crucial for Your Health

What Is the Gut Microbiome?

Bacteria, viruses, fungi and other microscopic living things are referred to as microorganisms, or microbes, for short.

Trillions of these microbes exist mainly inside your intestines and on your skin.

Most of the microbes in your intestines are found in a “pocket” of your large intestine called the cecum, and they are referred to as the gut microbiome.

Although many different types of microbes live inside you, bacteria are the most studied.

In fact, there are more bacterial cells in your body than human cells. There are roughly 40 trillion bacterial cells in your body and only 30 trillion human cells. That means you are more bacteria than human (12).

What’s more, there are up to 1,000 species of bacteria in the human gut microbiome, and each of them plays a different role in your body. Most of them are extremely important for your health, while others may cause disease (3).

Altogether, these microbes may weigh as much as 2–5 pounds (1–2 kg), which is roughly the weight of your brain. Together, they function as an extra organ in your body and play a huge role in your health.

How Does It Affect Your Body?

Humans have evolved to live with microbes for millions of years.

During this time, microbes have learned to play very important roles in the human body. In fact, without the gut microbiome, it would be very difficult to survive.

The gut microbiome begins to affect your body the moment you are born.

You are first exposed to microbes when you pass through your mother’s birth canal. However, new evidence suggests that babies may come in contact with some microbes while inside the womb (456).

As you grow, your gut microbiome begins to diversify, meaning it starts to contain many different types of microbial species. Higher microbiome diversity is considered good for your health (7).

Interestingly, the food you eat affects the diversity of your gut bacteria.

As your microbiome grows, it affects your body in a number of ways, including:

Therefore, there are a number of different ways in which the gut microbiome can affect key bodily functions and influence your health.

The Gut Microbiome May Affect Your Weight

There are thousands of different types of bacteria in your intestines, most of which benefit your health.

However, having too many unhealthy microbes can lead to disease.

An imbalance of healthy and unhealthy microbes is sometimes called gut dysbiosis, and it may contribute to weight gain (21).

Several well-known studies have shown that the gut microbiome differed completely between identical twins, one of whom was obese and one of whom was healthy. This demonstrated that differences in the microbiome were not genetic (2223).The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus New Insights into Old Diseases. | Gut microbiota, obesity and diabetes

Interestingly, in one study, when the microbiome from the obese twin was transferred to mice, they gained more weight those that had received the microbiome of the lean twin, despite both groups eating the same diet (22). Child Weight Gain Trajectories Linked To Oral Microbiota Composition |  Cultured gut microbiota from twins discordant for obesity modulate adiposity and metabolic phenotypes

These studies show that microbiome dysbiosis may play a role in weight gain.

Fortunately, probiotics are good for a healthy microbiome and can help with weight loss. Nevertheless, studies suggest that the effects of probiotics on weight loss are probably quite small, with people losing less than 2.2 pounds (1 kg) (24). Effect of probiotics on body weight and body-mass index | Using probiotics in clinical practice Where are we now

It Affects Gut Health

The microbiome can also affect gut health and may play a role in intestinal diseases like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) (252627). Probiotics for the treatment of depressive symptoms An anti-inflammatory mechanism | Gut microbiota role in irritable bowel syndrome New therapeutic strategies |  Dynamics of the human gut microbiome in inflammatory bowel disease.  |   Irritable bowel syndrome A microbiome-gut-brain axis disorder

The bloating, cramps and abdominal pain that people with IBS experience may be due to gut dysbiosis. This is because the microbes produce a lot of gas and other chemicals, which contribute to the symptoms of intestinal discomfort (28). Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome

However, certain healthy bacteria in the microbiome can also improve gut health.

Certain Bifidobacteria and Lactobacilli, which are found in probiotics and yogurt, can help seal gaps between intestinal cells and prevent leaky gut syndrome.

These species can also prevent disease-causing bacteria from sticking to the intestinal wall (2930).Intestinal permeability – a new target for disease prevention and therapy

In fact, taking certain probiotics that contain Bifidobacteria and Lactobacilli can reduce symptoms of IBS (31). Meta-analysis of probiotics for the treatment of irritable bowel syndrome.Treating irritable bowel syndrome with probiotics the evidence

The Gut Microbiome May Benefit Heart Health

Interestingly, the gut microbiome may even affect heart health (32).

A recent study in 1,500 people found that the gut microbiome played an important role in promoting “good” HDL cholesterol and triglycerides (33).Gut Microbiota and Cardiovascular Uremic Toxicities. |  The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

Certain unhealthy species in the gut microbiome may also contribute to heart disease by producing trimethylamine N-oxide (TMAO).

TMAO is a chemical that contributes to blocked arteries, which may lead to heart attacks or stroke.

Certain bacteria within the microbiome convert choline and L-carnitine, both of which are nutrients found in red meat and other animal-based food sources, to TMAO, potentially increasing risk factors for heart disease (343536). Gut microbiota metabolism of L-carnitine and cardiovascular risk. |  Feeding the microbiota-gut-brain axis diet, microbiome, and neuropsychiatry |  Time for food The impact of diet on gut microbiota and human health |  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease |  Gut Microbiota and Cardiovascular Uremic Toxicities. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids  | Role of carnitine and its derivatives in the development and management of type 2 diabetes.

However, other bacteria within the gut microbiome, particularly Lactobacilli, may help reduce cholesterol when taken as a probiotic (37). Effect of probiotic Lactobacillus on lipid profile A systematic review and meta-analysis of randomized, controlled trials. | Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals


Science and Politics of Nutrition_ Role of the gut microbiota in nutrition and health

It May Help Control Blood Sugar and Lower the Risk of Diabetes

The gut microbiome also may help control blood sugar, which could affect the risk of type 1 and 2 diabetes.

One recent study examined 33 infants who had a genetically high risk of developing type 1 diabetes.

It found that the diversity of the microbiome dropped suddenly before the onset of type 1 diabetes. It also found that levels of a number of unhealthy bacterial species increased just before the onset of type 1 diabetes (38). Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer. |  The Dynamics of the Human Infant Gut Microbiome in Development and in Progression towards Type 1 Diabetes

Another study found that even when people ate the exact same foods, their blood sugar could vary greatly. This may be due to the types of bacteria in their guts (39). Personalized Nutrition by Prediction of Glycemic responses |  Cell-Specific Competition for Calories Drives Asymmetric Nutrient-Energy Partitioning, Obesity, and Metabolic Diseases in Human and Non-human Animals.

Added sugars drive nutrient and energy deficit in obesity a new paradigm

It May Affect Brain Health

The gut microbiome may even benefit brain health in a number of ways.

First, certain species of bacteria can help produce chemicals in the brain called neurotransmitters. For example, serotonin is an antidepressant neurotransmitter that’s mostly made in the gut (4041). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. | ADHD-originating in the gut The emergence of a new explanatory model

Second, the gut is physically connected to the brain through millions of nerves.

Therefore, the gut microbiome may also affect brain health by helping control the messages that are sent to the brain through these nerves (4243).

A number of studies have shown that people with various psychological disorders have different species of bacteria in their guts, compared to healthy people. This suggests that the gut microbiome may affect brain health (4445).Altered fecal microbiota composition in patients with major depressive disorder. |  Liking and wanting linked to Reward Deficiency Syndrome (RDS) |  Addiction and brain reward and antireward pathways |  Correlation of tryptophan metabolites with connectivity of extended central reward network in healthy subjects. |  Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.

However, it’s unclear if this is simply due to different dietary and lifestyle habits.

A small number of studies have also shown that certain probiotics can improve symptoms of depression and other mental health disorders (4647). The Gut-Brain Axis, the Human Gut Microbiota and Their Integration in the Development of Obesity |  Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters brain activity  | Altered fecal microbiota composition in patients with major depressive disorder.

How Can You Improve Your Gut Microbiome?

There are many ways to improve your gut microbiome, including:


Leaky Gut Syndrome

Is Leaky Gut Syndrome a Real Condition? An Unbiased Look

A phenomenon called “leaky gut” has gained quite a bit of attention lately, particularly among natural health enthusiasts.

Leaky gut, also known as increased intestinal permeability, is a digestive condition in which bacteria and toxins are able to “leak” through the intestinal wall.

Mainstream medical professionals do not recognize leaky gut as a real condition.

However, there is quite a bit of scientific evidence that leaky gut does exist and may be associated with multiple health problems.

This article takes a critical look at the evidence on leaky gut syndrome.

What Is Leaky Gut?

The human digestive tract is where food is broken down and nutrients are absorbed.

The digestive system also plays an important role in protecting your body from harmful substances. The walls of the intestines act as barriers, controlling what enters the bloodstream to be transported to your organs.

Small gaps in the intestinal wall called tight junctions allow water and nutrients to pass through, while blocking the passage of harmful substances. Intestinal permeability refers to how easily substances pass through the intestinal wall.

When the tight junctions of intestinal walls become loose, the gut becomes more permeable, which may allow bacteria and toxins to pass from the gut into the bloodstream. This phenomenon is commonly referred to as “leaky gut.”

When the gut is “leaky” and bacteria and toxins enter the bloodstream, it can cause widespread inflammation and possibly trigger a reaction from the immune system.

Supposed symptoms of leaky gut syndrome include bloating, food sensitivities, fatigue, digestive issues and skin problems (1).

However, leaky gut is not a recognized medical diagnosis. In fact, some medical professionals deny that it even exists.

Proponents claim that it’s the underlying cause of all sorts of conditions, including chronic fatigue syndrome, migraines, multiple sclerosis, fibromyalgia, food sensitivities, thyroid abnormalities, mood swings, skin conditions and autism.

The problem is that very few scientific studies mention leaky gut syndrome.

Nevertheless, medical professionals do agree that increased intestinal permeability, or intestinal hyperpermeability, exists in certain chronic diseases (12).

What Causes Leaky Gut?

Leaky gut syndrome remains a bit of a medical mystery, and medical professionals are still trying to determine exactly what causes it.

A protein called zonulin is the only known regulator of intestinal permeability (34).

When it’s activated in genetically susceptible people, it can lead to leaky gut. Two factors that trigger the release of zonulin are bacteria in the intestines and gluten, which is a protein found in wheat and other grains (345).

However, some studies have shown that gluten only increases intestinal permeability in people with conditions like celiac disease or irritable bowel syndrome (67).

There are likely multiple contributing factors to leaky gut syndrome.

Below are a few factors that are believed to play a role:

  • Excessive sugar intake: An unhealthy diet high in sugar, particularly fructose, harms the barrier function of the intestinal wall (89).
  • Non-steroidal anti-inflammatory drugs (NSAIDs): The long-term use of NSAIDs like ibuprofen can increase intestinal permeability and contribute to leaky gut (101112).
  • Excessive alcohol intake: Excessive alcohol intake may increase intestinal permeability (1013).
  • Nutrient deficiencies: Deficiencies in vitamin A, vitamin D and zinc have each been implicated in increased intestinal permeability (81415).
  • Inflammation: Chronic inflammation throughout the body can contribute to leaky gut syndrome (16).
  • Stress: Chronic stress is a contributing factor to multiple gastrointestinal disorders, including leaky gut (17).
  • Poor gut health: There are millions of bacteria in the gut, some beneficial and some harmful. When the balance between the two is disrupted, it can affect the barrier function of the intestinal wall (18).
  • Yeast overgrowth: Yeast is naturally present in the gut, but an overgrowth of yeast may contribute to leaky gut (18).
Diseases Associated With Leaky Gut

The claim that leaky gut is the root of modern health problems has yet to be proven by science. However, many studies have connected increased intestinal permeability with multiple chronic diseases (3).

Celiac Disease

Celiac disease is an autoimmune disease characterized by a severe sensitivity to gluten.

Several studies have found that intestinal permeability is higher in patients with celiac disease (167).

In fact, one study found that ingesting gluten significantly increases intestinal permeability in celiac patients immediately after consumption (6).


There is some evidence that increased intestinal permeability plays a role in the development of type 1 diabetes (1).

Type 1 diabetes is caused by an autoimmune destruction of insulin-producing beta cells in the pancreas (19).

It has been suggested that the immune reaction responsible for beta cell destruction may be triggered by foreign substances “leaking” through the gut (2021).

One study found that 42% of individuals with type 1 diabetes had significantly elevated zonulin levels. Zonulin is a known moderator of intestinal permeability (22).

In an animal study, rats that developed diabetes were found to have abnormal intestinal permeability prior to developing diabetes (23).

Crohn’s Disease

Increased intestinal permeability plays a significant role in Crohn’s disease. Crohn’s is a chronic digestive disorder characterized by persistent inflammation of the intestinal tract (12425).

Several studies have observed an increase in intestinal permeability in patients with Crohn’s disease (2627.)

A few studies also found increased intestinal permeability in relatives of Crohn’s patients, who are at an increased risk of developing the disease (2628).

This suggests that increased permeability may be connected to the genetic component of Crohn’s disease.

Irritable Bowel Syndrome

Studies have found that people with irritable bowel syndrome (IBS) are likely to have increased intestinal permeability (2930).

IBS is a digestive disorder characterized by both diarrhea and constipation. One study found that increased intestinal permeability is particularly prevalent in those with diarrhea-predominant IBS (31).

Food Allergies

A few studies have shown that individuals with food allergies often have impaired intestinal barrier function (3233).

A leaky gut may allow food proteins to cross the intestinal barrier, stimulating an immune response. An immune response to a food protein, which is known as an antigen, is the definition of a food allergy (10).


Is Leaky Gut a Cause or Symptom of Disease?

Proponents of leaky gut syndrome claim it’s the underlying cause of most modern health problems.

Indeed, plenty of studies have shown that increased intestinal permeability is present in several chronic diseases, specifically autoimmune disorders.

However, it is difficult to prove that leaky gut is the cause of disease.

Skeptics argue that increased intestinal permeability is a symptom of chronic disease, rather than an underlying cause (34).

Interestingly, animal studies on celiac disease, type 1 diabetes and IBS have identified increased intestinal permeability prior to the onset of disease (233435).

This evidence supports the theory that leaky gut is involved in the development of disease.

On the other hand, a study found that intestinal permeability in people with celiac disease returned to normal in 87% of people who followed a gluten-free diet for over a year. A gluten-free diet is the standard treatment for celiac disease (36).

This suggests that the abnormal intestinal permeability may be a response to gluten ingestion, rather than the cause of celiac disease.

Overall, there is not yet sufficient evidence to prove that leaky gut is the underlying cause of chronic diseases.

Some Claims About Leaky Gut Syndrome Are Not Backed by Science

There is enough evidence to demonstrate that leaky gut syndrome does exist. However, some of the claims being made are not backed by science.

Proponents of leaky gut have claimed that it’s connected to a wide variety of ailments, including autism, anxiety, depression, eczema and cancer. Most of these claims have yet to be proven by scientific studies.

A few studies have found that a proportion of autistic children have increased intestinal permeability, but other studies have found that intestinal permeability was normal (373839).

Currently, there are no studies that show leaky gut presence prior to the onset of autism, which means there is no evidence that it is a causative factor.

There is some evidence that bacteria crossing the intestinal wall may play a role in anxiety and depression, but more research is needed to prove this possible connection (404142).

The results of studies on eczema and intestinal permeability have been inconsistent, and there is currently no scientific basis for the claim that leaky gut leads to cancer (434445).

Furthermore, some of the proposed treatments for leaky gut syndrome have weak scientific support.

Many supplements and remedies being sold by websites have not yet been proven to be effective (34).

How to Improve Your Gut Health

Leaky gut syndrome is not an official medical diagnosis and there is not yet a recommended course of treatment.

Nevertheless, there are steps you can take to improve your gut health. One of the keys to a healthier gut is increasing the number of beneficial bacteria in it.

Here are a few strategies to support a healthy gut:

Some Probiotics May Prevent Weight Gain

Losing weight is not the only way to fight obesity. Prevention is even more important, as in preventing the weight from accumulating in the first place.

In one 4-week study, taking a probiotic formulation called VSL#3 reduced weight gain and fat gain on a diet where people were overfed by 1000 calories per day (26). The Gut Microbiome and Its Role in Obesity. |  Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults.

On this graph, you can see how the probiotic group gained significantly less fat:

This indicates that some probiotic strains might be effective at preventing weight gain in the context of a high-calorie diet. However, this needs to be studied a lot more.

Some Probiotic Strains May Increase the Risk of Weight Gain and Obesity

Not all studies have found that probiotics help with weight loss.

Some studies have even found that certain probiotic strains might lead to weight gain, not loss. This includes Lactobacillus acidophilus (27).Comparative meta-analysis of the effect of Lactobacillus species on weight gain

One recent study reviewed 4 controlled clinical studies. It concluded that probiotics did not reduce body weight, BMI or body fat levels in overweight or obese adults (28).

However, this review study did not include many of the studies mentioned above.

Probiotics May Be One Part of The Puzzle

Probiotics offer a wide range of health benefits.

However, their effects on weight are mixed, and seem to depend on the type of probiotic.

Evidence indicates that Lactobacillus gasseri may help people with obesity lose weight and belly fat. Additionally, a blend of probiotics called VSL#3 may reduce weight gain on a high-calorie diet.

At the end of the day, certain types of probiotics may have modest effects on your weight, especially when combined with a healthy, real food-based diet.

Nevertheless, there are many other reasons to take a probiotic supplement besides weight loss.

They can improve digestive health, reduce inflammation, improve cardiovascular risk factors and even help fight depression and anxiety.

8 Surprising Things That Harm Your Gut Bacteria

The human gut is home to over 100 trillion bacteria, known as the “gut flora.” Having a healthy gut flora is incredibly important for your overall health.

Interestingly, many diet, lifestyle and other environmental factors can negatively affect your gut bacteria.

What Are Gut Bacteria and Why Are They Important?

Hundreds of species of bacteria reside in your gut. Some of them are friendly, while others are not.

Most bacteria in the gut belong to one of four groups: FirmicutesBacteroidetesActinobacteriaor Proteobacteria (12).

Each group plays a role in your health and requires different nutrients for growth (3).

The friendly gut bacteria are important for digestion. They destroy harmful bacteria and other microorganisms and produce vitamin K, folate and short-chain fatty acids (45).

When the gut flora contains too many harmful bacteria and not enough friendly bacteria, an imbalance can occur. This is known as dysbiosis (67).

Both dysbiosis and a reduction in gut flora diversity have been linked to insulin resistance, weight gain, inflammation, obesity, inflammatory bowel disease and colorectal cancer (891011).

Therefore, it’s important to keep your gut bacteria as friendly and abundant as possible.

Without further ado, here are 8 surprising things that can cause harm to your gut bacteria.

1. Not Eating a Diverse Range of Foods

Generally, a rich and diverse gut flora is considered to be a healthy one (12).

A lack of diversity within the gut bacteria limits recovery from harmful influences, such as infection or antibiotics (1314).

A diet consisting of a wide variety of whole foods, such as fruits, vegetables and whole grains, can lead to a more diverse gut flora. In fact, changing up your diet can alter your gut flora profile after only a few days (121516).

This is because the food you eat provides nutrients that help bacteria grow. A diet rich in whole foods provides your gut with a variety of nutrients that help promote the growth of different types of bacteria, resulting in a more diverse gut flora.

Unfortunately, over the past 50 years, much of the diversity in the Western diet has been lost. Today, 75% of the world’s food supply comes from only 12 plants and five animal species (12).

Interestingly, studies show that those living in rural regions of Africa and South America have a more diverse gut flora than those living in the US and Europe (1718).

Their diets are generally unaffected by the Western world and are rich in fiber and a variety of plant protein sources.

2. Lack of Prebiotics in the Diet

Prebiotics are a type of fiber that passes through the body undigested and promotes the growth and activity of friendly gut bacteria (19).

Many foods, including fruits, vegetables and whole grains, naturally contain prebiotic fiber.

A lack of them in the diet may be harmful to your overall digestive health (20).

Foods high in prebiotics include:

  • Lentils, chickpeas and beans
  • Oats
  • Bananas
  • Jerusalem artichokes
  • Asparagus
  • Garlic
  • Leeks
  • Onions
  • Nuts

One study in 30 obese women found that taking a daily prebiotic supplement for three months promoted the growth of the healthy bacteria Bifidobacterium and Faecalibacterium (21).

Prebiotic fiber supplements also promote the production of short-chain fatty acids (22).

These fatty acids are the main nutrient source for the cells in your colon. They can be absorbed into your blood, where they promote metabolic and digestive health, reduce inflammation and can reduce the risk of colorectal cancer (2324).

Moreover, foods rich in prebiotic fiber may play a role in reducing insulin and cholesterol levels (2526).

3. Drinking Too Much Alcohol

Alcohol is addictive, highly toxic and can have harmful physical and mental effects when consumed in large amounts (2728).

In terms of gut health, chronic alcohol consumption can cause serious problems, including dysbiosis.

One study examined the gut flora of 41 alcoholics and compared them to 10 healthy individuals who consumed little-to-no alcohol. Dysbiosis was present in 27% of the alcoholic population, but it was not present in any of the healthy individuals (29).

Another study compared the effects of three different types of alcohol on gut health.

For 20 days, each individual consumed 9.2 ounces (272 ml) of red wine, the same amount of de-alcoholized red wine or 3.4 ounces (100 ml) of gin each day (30).

Gin decreased the number of beneficial gut bacteria, whereas red wine actually increased the abundance of bacteria known to promote gut health and decreased the number of harmful gut bacteria like Clostridium.

The beneficial effect of moderate red wine consumption on gut bacteria appears to be due to its polyphenol content.

Polyphenols are plant compounds that escape digestion and are broken down by gut bacteria. They may also help reduce blood pressure and improve cholesterol (3132).

4. Antibiotic Use

Antibiotics are important medicines used to treat infections and diseases caused by bacteria, such as urinary tract infections and strep throat. They work by either killing bacteria or preventing them from multiplying and have saved millions of lives over the past 80 years.

However, one of their drawbacks is that they affect both good and bad bacteria. In fact, even a single antibiotic treatment can lead to harmful changes in the composition and diversity of the gut flora (333435).

Antibiotics usually cause a short-term decline in beneficial bacteria, such as Bifidobacteria and Lactobacilli, and can temporarily increase harmful bacteria like Clostridium (36).

However, antibiotics can also lead to long-term alterations in the gut flora. After completing a dose of antibiotics, most bacteria return after 1–4 weeks, but their numbers often don’t return to previous levels (373839).

In fact, one study found that a single dose of antibiotics reduced the diversity of Bacteroides, one of the most dominant bacterial groups, and increased the number of resistant strains. These effects remained for up to two years (40).

5. Lack of Regular Physical Activity

Physical activity is simply defined as any movement of the body that burns energy.

Walking, gardening, swimming and cycling are all examples of physical activity.

Being physically active has a number of health benefits, including weight loss, lower stress levels and a reduced risk of chronic disease (41424344).

What’s more, recent studies suggest that physical activity may also alter the gut bacteria, improving gut health (454647).

Higher fitness levels have been associated with a greater abundance of butyrate, a short-chain fatty acid that’s important for overall health, and butyrate-producing bacteria (4849).

One study found that professional rugby players had a more diverse gut flora and twice the number of bacterial families, compared to the control groups matched for body size, age and gender (50).

Moreover, athletes had higher levels of Akkermansia, a bacteria shown to play an important role in metabolic health and the prevention of obesity (5051).

Similar results have been reported in women.

A study compared the gut flora of 19 physically active women to 21 non-active women (52).

Active women had a higher abundance of health-promoting bacteria, including Bifidobacteriumand Akkermansia, suggesting that regular physical activity, even at low-to-moderate intensities, can be beneficial.

6. Cigarette Smoking

Tobacco smoke is made up of thousands of chemicals, 70 of which can cause cancer (53).

Smoking causes harm to nearly every organ in the body and raises the risk of heart disease, stroke and lung cancer (54).

Cigarette smoking is also one of the most important environmental risk factors for inflammatory bowel disease, a disease characterized by ongoing inflammation of the digestive tract (55).

Furthermore, smokers are twice as likely to have Crohn’s disease, a common type of inflammatory bowel disease, compared to non-smokers (56).

In one study, smoking cessation increased gut flora diversity, which is a marker of a healthy gut (57).

7. Not Getting Enough Sleep

Getting good sleep is very important for overall health.

Studies show that sleep deprivation is linked to many diseases, including obesity and heart disease (585960).

Sleep is so important that your body has its own time-keeping clock, known as your circadian rhythm (61).

It’s a 24-hour internal clock that affects your brain, body and hormones. It can keep you alert and awake, but it can also tell your body when it’s time to sleep (6263).

It appears that the gut also follows a daily circadian-like rhythm. Disrupting your body clock through a lack of sleep, shift work and eating late at night may have harmful effects on your gut bacteria (646566).

A 2016 study was the first to explore the effects of short-term sleep deprivation on the composition of gut flora (67).

The study compared the effects of two nights of sleep deprivation (about 4 hours per night) versus two nights of normal sleep duration (8.5 hours) in nine men.

Two days of sleep deprivation caused subtle changes to the gut flora and increased the abundance of bacteria associated with weight gain, obesity, type 2 diabetes and fat metabolism (6768).

Nevertheless, sleep deprivation’s effects on gut bacteria is a new area of research. Further studies are required to determine the impact of sleep loss and poor sleep quality on gut health.

8. Too Much Stress

Being healthy isn’t only about diet, physical activity and adequate sleep.

High stress levels can also have harmful effects on the body. In the gut, stress can increase sensitivity, reduce blood flow and alter the gut bacteria (69).

Studies in mice have shown that different types of stress, such as isolation, crowding and heat stress, can reduce gut flora diversity and alter gut profiles (707172).

Stress exposure in mice also affects bacterial populations, causing an increase in potentially harmful bacteria like Clostridium and reducing beneficial populations of bacteria like Lactobacillus (7374).

One study in humans looked at the effect of stress on the composition of gut bacteria in 23 college students (75).

The composition of gut bacteria was analyzed at the beginning of the semester and at the end of the semester during final examinations.

The high stress associated with final exams caused a reduction in friendly bacteria, including Lactobacilli.

While promising, research on the relationship between stress and gut flora is fairly new, and human studies are currently limited.

How to Improve Gut Health

A healthy gut flora that’s high in friendly bacteria is essential for overall health.

Here are some tips on how to improve your gut flora:

  • Eat more prebiotic foods: Eat plenty of foods rich in prebiotic fibers, such as legumes, onions, asparagus, oats, bananas and others.
  • Consume more probiotics: Probiotics may increase the abundance of healthy gut bacteria. Fermented foods, such as yogurt, kimchi, kefir and tempeh, are all excellent sources. You could also start taking a probiotic supplement.
  • Make time for quality sleep: To improve sleep quality, try cutting out caffeine late in the day, sleeping in complete darkness and making a structured sleep routine so that you go to sleep and wake up at the same time each day.
  • Reduce stress: Regular exercise, meditation and deep breathing exercises may help reduce your stress levels. If you regularly feel overwhelmed with stress, you may want to consider seeing a psychologist.
  • Eat foods rich in polyphenols: Good sources include blueberries, red wine, dark chocolate and green tea. Polyphenols are not digested very efficiently and often make their way to the colon, where they are digested by bacteria.


Diet Review

Diets aren’t one size fits all–which is why there’s no perfect diet for everyone. Research agrees: the best diet is the one that you, as an individual, can stick to. That means that the diet you find to be most successful might not be the same one that worked for your your best friend. And that’s okay. Some people do better with rules and restrictions, while others prefer looser diet guidelines. We’ve reviewed the most popular and highly ranked diets here, providing an overview as well as the advantages and disadvantages of each.


The DASH Diet was developed by the National Heart, Lung, and Blood Institute to prevent or reduce high blood pressure (DASH stands for Dietary Approaches to Stop Hypertension). Its hallmark characteristics are low fat and low salt; it encourages consumption of lots of fruits and vegetables, whole grains, nuts, poultry, and fish while limiting sweets, sugar-sweetened beverages, and red meat. These guidelines serve the purpose of reducing overall sodium intake to below 2300 mg, saturated fat to under 6% of daily caloric intake, and limiting cholesterol to 150 mg. High servings of fruits, vegetables, and low-fat dairy mean you’ll get plenty of heart-healthy potassium, as well as magnesium, calcium, phosphorus, and fiber. Research has found that following the DASH Diet can reduce systolic blood pressure between 2-7 mm/Hg, and each 5 mm/Hg reduction in blood pressure may reduce your risk of developing coronary artery disease by 15% and stroke by 27%.


The DASH Diet is nutritionally balanced and emphasizes whole foods, and because it doesn’t outlaw any specific foods—just discourages them—it’s sustainable for the long-term. Although it wasn’t originally designed as a weight loss diet, studies have shown that it can be effective in helping you lose weight. A 2010 study found that obese individuals who followed the DASH Diet, attended weight loss classes, and exercised regularly lost an average of 19 pounds over four months. There are plenty of recipes that fit the DASH Diet, and because it’s supported in the medical journals, you can likely lean on dietitians or doctors for support.


The average man currently eats 4,200 mg of salt today and women consume about 3,300 mg. Reducing those numbers to 2,300 mg can be difficult, especially if many of the foods you rely on are packaged or processed. But foods included in the DASH Diet are naturally low in sodium, which gives you a little more freedom with the salt shaker. Eating out can be difficult, as restaurant meals are often loaded with fat, salt, and sugar. And because it discourages processed foods, meal prepping and cooking might take up more of your time.


The Flexitarian Diet—coined by Registered Dietitian Dawn Jackson Blatner in her 2009 book—is a plant-based diet that celebrates vegetarian nutrition while still allowing you to consume small amounts of meat and fish. Rather than focusing on the exclusion of certain foods, the diet focuses on adding in five food groups: plant-based proteins like soy, beans, lentils, peas, nuts, seeds, and eggs; fruits and vegetables; dairy; whole grains; and flavor boosters—including spices and chocolate. Beginner flexitarians generally avoid meat two days a week; advanced flexitarians skip it four days a week; and expert flexitarians enjoy meat-free meals five days a week. In addition to outlining what is involved in the flexitarian diet, Blatner’s book also provides the tools needed to build a sustainable healthy lifestyle. To keep things simple, her book is based around the theme of five. She provides a five-week meal plan along with more than 100 recipes, as well as five “Flex Fitness Factors” to help you build a solid exercise foundation, and five “FlexLife troubleshooters” intended to help you make sustainable changes to your diet. Blatner encourages her readers to make small changes one at a time instead of making a complete diet overhaul.


Plenty of research has found that a plant-based diet can lead to improved health. In addition to helping you lose weight, the Flexitarian Diet might also help reduce your risk for heart disease, diabetes, and cancer. Blatner’s book and her strategies are backed by evidence as well as tried-and-true tips—as a registered dietitian, Blatner has worked with many clients in helping them achieve their weight loss goals, so she knows firsthand what works and what doesn’t. The Flexitarian Diet provides much more leeway than other weight loss diets–eating out and drinking alcohol both fit into the program.


If you don’t already like fruits and vegetables, this diet might be hard to follow. And if you don’t like to cook, you might have trouble following the guidelines and recipes. While flexibility allows you to eat the foods you want when you want them, that lack of structure might mean slower weight loss for some.


Jenny Craig offers a variety of services designed to help support you on your weight loss journey – from delivered low-calorie meals and individualized exercise programs to one-on-one nutritional counseling and access to online tools. Unlike other diet plans that forbid certain foods and food groups, as you near your goal weight, Jenny Craig allows you to eat what you want—provided that splurges, like alcohol, are occasional indulgences. Calories range from about 1,200-2,300, depending on your height and weight and a number of other individual factors like exercise level and goals.

Jenny Craig has four phases. The first phase is the most restrictive and from there you are gradually given more autonomy over what you eat and when you eat. This slow gradual process allows you to learn the skills you need in order to lose weight and keep it off.

In the first phase you consume exclusively Jenny Craig’s pre-packaged meals within a 12 hour time frame, from 8am to 8pm. This allows you to take advantage of your circadian rhythm and eat during the time when your metabolism is naturally the fastest. During the second phase, you still stick with the meals provided by Jenny Craig, but you are not eating within a time restricted window and you are provided with more food options. These first two phases are designed to reacquaint members with healthy foods and appropriate portion sizes. During the third phase of the diet—at which point you’re nearing your goal weight—your nutritional consultant will help you transition to cooking at home and eating out, providing sustainable strategies to help you stick to healthy eating habits in the long-term. You’ve reached the final stage when you’ve achieved your goal weight, and this “maintenance” phase lasts for life.


Nutritional consultants aren’t necessarily credentialed health professionals, but their training is based off of a curriculum developed by registered dietitians. Most notably, many of the nutritional consultants are former Jenny Craig members themselves, so they are familiar with the diet and struggles that come with it. Convenience is top notch for Jenny Craig members: in the first half, the guesswork of figuring out what to have for dinner is removed entirely. Jenny Craig also has the advantage of providing its members with a strong support crew, including a personal consultant, weight loss coach, and member-exclusive blogs and forums. From a nutrition standpoint, the Jenny Craig diet is nutritionally balanced—and you won’t have to say goodbye to any of your favorite foods. As a weight loss plan, studies have shown that Jenny Craig can be effective; in a review of commercial weight loss plans, Jenny Craig participants lost the most weight over 12 months.


Jenny Craig can be costly. The initial trial period of 12 days is only $16 plus the cost of food (around $20 per day), but if you want to continue with Jenny Craig after this trial period the least expensive membership costs $19.00 per month plus a $49 enrollment fee. Premium membership is a $299 one time payment plus the cost of food.


The Mayo Clinic Diet, branded “a weight loss program for life,” is designed to help you lose pounds consistently until you reach your goal weight—and then maintain that for life. It’s backed by the Mayo Clinic, so it also has strong clinical research to back up its efficacy. Instead of eating already-prepared meals or drastically cutting out food groups, you’ll learn strategies to help you adopt healthier eating patterns and behaviors.

The diet has two phases. In the Lose It! phase, which lasts two weeks, you’ll aim to lose 6 to 10 pounds by adopting five healthy habits (like adding a healthy breakfast) and breaking five unhealthy habits (for example, removing added sugars and refraining from eating while watching TV). In the Live It! phase—which is meant to be a sustainable eating pattern for life—you’ll gain more tools to help you eat healthfully, including meal planning, and sticking to portion sizes. The goal is to lose 1 to 2 pounds per week until you reach your goal weight. In both phases, exercise is also considered a priority.

In terms of actual food, the Mayo Clinic Diet emphasizes lots of fresh fruits and vegetables as well as whole grain or fiber-rich carbohydrates, lean proteins, low-fat dairy, and heart-healthy fats. You won’t have to eliminate any favorite foods, although alcohol should be considered a treat, not an everyday indulgence.


No foods are completely forbidden in the Live It! stage, which makes the diet sustainable for life and much easier to stick to. In a 2008 pilot program, 53 obese participants lost an average of 8 pounds in the first two weeks; almost everybody lost at least 4 pounds, with many non-obese participants losing between 6 and 8 pounds. Because the diet emphasizes nutrient-rich, low-calorie foods that tend to be high in fiber or water content, like fruits and veggies, you should feel full enough even though you’re eating fewer calories than you’re used to. Membership and access to all online resources is also inexpensive (only $4 a week) and never requires you to count calories!!


Because the Mayo Clinic Diet emphasizes whole foods you’ll probably do more cooking and rely less on packaged snacks. This can can take up more time than popping a frozen pizza in the oven. The cost of whole, unprocessed food might be also be higher than processed convenience foods, but because you can pick your own recipes, you can plan them around cheaper seasonal veggies.


The Mediterranean Diet is one of the most well-known diets, and for good reason. It’s consistently ranked near the top of US News’ Best Diets in categories like Best Diets Overall, Best Diets for Healthy Eating, and Best Heart-Healthy Diets. The Mediterranean Diet is more of an eating pattern rather than a diet. It doesn’t explicitly provide calorie limits, but it does emphasize an eating pattern that prioritizes plant-based foods like fruits, vegetables, nuts, and grains and healthy fats like olive oil and fatty fish while limiting red meat and high fat dairy. It’s based off of research that shows that populations that typically eat this way—in the countries that border the Mediterranean Sea—tend to have lower rates of death from heart disease as well as lower LDL cholesterol levels.


Since the Mediterranean Diet doesn’t ban any foods, it’s more sustainable and easier to follow in the long-term than other more restrictive weight loss plans. In fact, it even allows dieters to enjoy a glass of wine at night (but there’s no need to start drinking wine if you don’t already). Following the Mediterranean Diet can benefit your health in a number of different ways. In addition to potentially leading to weight loss, it can help you reduce the risk of developing chronic diseases such as heart disease, diabetes, or cancer.


The diet encourage eating healthy fats like those found in nuts, seeds, fish, and certain oils. Since fats are higher in calories ounce for ounce than protein and carbs, it’s important to put a cap on fat intake, regardless of the source, if you’re concerned about weight control. The Mediterranean Diet isn’t specifically designed as a weight loss diet, so if that’s your goal, be sure to pay attention to portion sizes.


The goal of Nutrisystem is to simplify weight loss: the plan is a 28-day program that sends prepackaged meals and snacks right to your door. In the first week (“Turbo Takeoff”), you’ll eat around 1000 calories daily of predetermined Nutrisystem meals, shakes and snacks high in protein and fiber. After that your calorie intake increases to about 1,200 calories a day for women and 1, 500 calories a day for men. In the following weeks you are given the freedom to choose from a variety of different food options, depending on which package you select: “Basic” provides preselected meals; “Core” offers more choices as well as the Favorites Pack; and “Uniquely Yours” provides over 150 different options for meals and snacks. There are also plans to accommodate those with diabetes, vegetarians, and a special package for men who have slightly higher calorie requirements.

The calorie-controlled meal plans are designed to help you lose one to two pounds a week. You’ll need to supplement your meals with some approved grocery store items, including fruits, veggies, protein sources, and low-fat dairy.


If convenience is what you’re looking for, Nutrisystem is tops. You can pick a month’s worth of meals in a few minutes—so you’ll definitely save time when it comes to meal planning, grocery shopping and meal prepping. You also won’t have to count any calories or worry about overeating, as Nutrisystem’s meals are pre-portioned (as long as you stick to the meal plans!). As an added benefit, users get access to an online community for support and other tools to monitor your progress. Studies have shown that Nutrisystem can be effective in helping you lose weight: in one study, diabetic participants on the Nutrisystem Diet track lost an average of 15 pounds over 3 months, compared to just one in a control group.


While the cost varies from plan to plan, expect to pay about $300-$400 for meals per month—in addition to whatever snacks you buy at the grocery store. Additionally, while Nutrisystem might be great for limiting calorie intake and portion sizes while you’re on it, it can be difficult to transition back to buying, preparing and eating real food. Eating out can be difficult, but the plan provides two “flex” meals per week to accommodate social gatherings and unexpected dinners out.


The Spark Solution Diet is the diet of choice of SparkPeople, an online weight loss and healthy living community. The diet is based off of the idea that it takes about two weeks to develop new healthy habits. To keep you on track, it provides strategies and tools for transforming negative habits into positive ones, as well as fourteen days of meal plans and exercise routines. Your daily meals are built off of nutritious foods that boost metabolism, plus eight glasses of water per day. Meal plans, which include three meals and a snack, provide roughly 1,500 calories a day and contain 45-65% carbohydrates, 20-35% fats, and 16-35% protein. No foods are completely off-limits, although dining out is frowned upon until week four.

The book focuses on three main components: the metabolic makeover, in which you support a healthy, humming metabolism by choosing healthy foods regularly (no skipping breakfast!); the mindset makeover, whereby you view healthy eating and exercise as necessary ingredients to live a full, active life; and the motivation and momentum makeover, whereby you use your own healthy momentum to stick with your new healthy habits (the better you feel, the more likely you are to continue with your healthy habits–which leads you to feel even better!).


When you combine exercise and a calorie intake of 1,500 calories, it’s highly likely you’ll create an energy deficit (burning more calories than you take in)—which equals weight loss. One of the strongest components of the diet is the community—SparkPeople has more than 15 million members who can provide troubleshooting, personal success stories and roadblocks, and new recipes through


If you’re not a planner, this diet might not be for you: the first 14 days are very specific and require advance planning and patience. It may also not be sustainable in the long term, as its success depends on sticking to the prescribed calorie counts and exercise.


The Therapeutic Lifestyle Changes diet was developed by the National Institutes of Health’s National Cholesterol Education Program in order to reduce high cholesterol levels. The main focus of the diet is to reduce the amount of saturated fat in your diet to less than 7% of total calories, but it provides specific percentages for other parts of your diet as well—including limiting carbohydrate intake to 50-60% of daily calories, protein to roughly 15% of calories, and cholesterol to less than 200 mg per day.

You’ll choose your calorie range depending on whether you’re just trying to reduce cholesterol levels (2,500 calories for men and 1,800 for women) or also want to lose weight (1,600 and 1,200 calories, respectively). If, after cutting saturated fat and cholesterol intake to the recommended levels for six weeks, you haven’t seen improvement in cholesterol levels, you’ll add in 2 grams of plant stanols or sterols and 10-25 grams of soluble fiber each day. Protein is kept to a minimum (less than 5 ounces per day of lean proteins like skinless chicken and fish), while vegetables, fruits, and whole grains are emphasized.


Studies support the TLC Diet’s efficacy in promoting heart health; in fact, it’s endorsed by the American Heart Association and is clinically shown to reduce cholesterol. It’s nutritionally balanced, and it supports long-term health.


As a diet whose intent is primarily cholesterol reduction, it may not be as effective as some other diets at promoting weight loss. In a study comparing the Atkins Diet and the TLC diet, TLC dieters lost 20 pounds over six months, which is a decent result for a healthy carb-based diet, but not as dramatic as the 31 pounds lost by Atkins Dieters. It’s also time-consuming: in addition to counting calories, you also have to calculate percentages of calories coming from different nutrients. Label reading is another task that might become tedious after a while.


According to Barbara Rolls, creator of the Volumetrics Diet, we can minimize hunger—and thus overeating–by keeping our stomachs full. But the trick is to fill up with nutrient-dense, high-volume foods like vegetables and broth-based soups, which take up space without too many calories. Energy density, the number of calories a food has per unit of volume, is a key concept in this diet and defines how foods are categorized. Category 1 (very low-density) includes non-starchy fruits and vegetables, nonfat milk, and broth-based soup; Category 2 (low-density) includes starchy fruits and vegetables, grains, lean proteins, and legumes; Category 3 (medium-density) includes smaller portions of bread products, desserts, higher-fat meats, and cheeses; and Category 4 (high-density) includes fried foods, candy, cookies, nuts, and other fats.

In three meals, two snacks, and dessert, you’ll prioritize foods from Categories 1 and 2 while sticking to smaller portions of the foods found in Categories 3 and 4. Unlike more regimented diet plans, Volumetrics is more of an eating philosophy, encouraging you to choose foods that are richer in nutrients and that will fill you up for fewer calories. There are no membership fees, but the Ultimate Volumetrics Diet book (available online for less than $15) does provide helpful guidance in addition to 125 recipes and menu planners.


Low-energy-dense, high-nutrient-dense diets have shown success in promoting weight loss, especially when the diets emphasize fruits and vegetables. Because the diet is designed to be filling, you won’t feel deprived or hungry. And it’s sustainable: it’s designed to shift your preferences towards naturally healthier foods while still allowing small portions of your favorite treats.


Grocery shopping, meal planning, and meal preparation can be time-consuming. And for people who have trouble with overeating and listening to their body’s signals, it may be difficult to find a point at which you’re truly satisfied without going over or under your body’s energy needs..


Weight Watchers allows you to eat whatever you want–provided that you stick within your allotted points, which are determined by age, gender, weight and height to provide a calorie deficit. In the newer SmartPoints program, which replaced the PointsPlus system, every food is assigned a value (there are more than 287,000 single ingredients are in their database). Nutrient-dense foods that are low in calories have fewer points than processed foods with empty calories; and in an effort to steer you towards whole, unprocessed foods and away from processed, low-fat foods, fruits and vegetables have zero points. Point values also take into consideration protein, sugar, and fat content. The overall goal of the program is to gradually shift you towards an overall healthier eating pattern—while helping you shed around two pounds per week.

There are three membership options. The most basic option is OnlinePlus. This give you access to an online community with thousands of recipes, tools, and success stories (in addition to the SmartPoints program, which helps you control your calorie intake, Weight Watchers also offers FitBreak, a new app that helps you achieve your exercise goals). The second option is Meetings. In addition to all the online resources, this membership provides you with access to weekly in-person meetings with other community members. And finally, the most inclusive membership option is Coaching. Through this membership you have access to all the benefits provided by the first two memberships as well as 24-hour access to a health coach. This coach will help you set up a plan that works with your lifestyle, habits, and schedule and provide you with on demand support.


You get to pick exactly which foods you eat on the plan, which means that any eating style—vegetarian, gluten free, vegan—can do well on this plan. In addition, you’ll still get to eat your favorite foods, whether it’s mashed potatoes or chocolate cake—as long as they fit into your daily allotment of points. Instead of being a quick fix for weight loss, Weight Watchers aims to provide sustainable tips for achieving consistent weight loss and maintenance over time—so you won’t be left in the dust after just one or two months. One of the biggest benefits of Weight Watchers is its support groups, meetings, and online community, which provide plenty of accountability and motivation. Users can choose what type of support they want (in-person or online) to best suit their needs.


Depending on the plan you select, Weight Watchers can be costly: you’ll pay $20 up front, and then a monthly fee between $19.95 and $54.95 depending on how much support you’d like. Weight Watchers may also allow too much freedom for some: in theory, you could choose to spend all of your daily points on chocolate chip cookies and still be “following the rules.” In this sense, self-motivation and accountability are necessary for success.

Popular Diets That Didn’t Make Our Top 10 List [And Why]

Some diets pop up again and again in the news—but despite their temporary surges in popularity, they may not be the healthiest or most effective strategies for weight loss. Read on to find out why:

About Ketosis

The Atkins Diet is known as the first popular (or widely used) low-carbohydrate diet in the US. The backbone of this plan is ketosis, a metabolic state that occurs when the body is deprived of carbohydrates and adjusts by burning metabolites of the incomplete breakdown of stored fats. It’s important to know that exact carbohydrate restrictions needed to reach ketosis vary from person to person, and that it’s also important to restrict protein intake in order to reach ketosis—a principle that the Atkins diet doesn’t explicitly espouse.


The Atkins Diet is a low-carbohydrate diet split into four phases. In Phase 1 (Induction), you eat fewer than 20 grams of carbohydrates per day for two weeks in order to kick-start weight loss; it includes foods high in protein and fat, and low-carb vegetables. In Phase 2 (Balancing), your carbohydrate intake increases as you are allowed to add small amounts of fruits, nuts, and more low-carb vegetables back into your diet; the aim is to add carbohydrates back into your diet while still losing weight. In Phase 3 (Fine-Tuning), which is implemented when you are close to your goal weight, you can add even more carbohydrates to your diet until weight loss plateaus. In Phase 4 (Maintenance), you eat an amount of carbohydrates that won’t promote weight gain. Proponents of the Atkins Diet suggest that how you eat in Phase 4 is how you should eat in general to maintain your goal weight. Foods that are encouraged on the Atkins Diet are meats, poultry, fish, seafood, eggs, full-fat dairy, nuts, seeds, and low-carb vegetables; sugar, grains, “diet” and “low fat” foods are limited; and high-carb vegetables (turnips, carrots), high-carb fruits (bananas, grapes), starches, and legumes are limited during the induction phase only.


Research does suggest that the Atkins Diet can promote weight loss. In addition, it emphasizes whole foods, making it naturally high in micronutrients like vitamins, minerals, and antioxidants. Unlike other weight loss diets, it doesn’t promote specific packaged foods or “diet” products, which gives you the freedom to choose which foods to include in your diet. The Atkins Diet is great for people who want some structure to their diet while also promoting balance: while it does limit carbohydrates pretty strictly, there’s no actual calorie counting—so there’s still plenty of freedom to enjoy many foods that other diets would normally limit. It’s also free—there are no membership fees or certain brands of food you have to buy (the only up-front cost would, potentially, be an educational book).


For many, the Atkins Diet (especially the induction phase) can be too strict. As you drastically cut your intake of carbohydrates, you may experience fatigue, bad breath and headaches. It also requires a lot of big changes all at once: cutting out many foods that you enjoy daily, like refined sugar, alcohol, and grains, can be more difficult than making small changes one at a time. And while it can lead to short-term weight loss, its sustainability in the long-term is questionable. In addition, its focus on fat and protein may have a negative impact on your heart health, and its strictness may lead to nutrient deficiencies.

Why it’s not a top diet

The Atkins Diet might work for short-term weight loss, but studies have not found that weight loss to be sustainable; in many studies, participants gained back some or all of the weight they had lost.


The Biggest Loser Diet is designed for people who want to eat and exercise like the participants on The Biggest Loser. If you are interested in this diet you have two options. The first is a self-guided weight loss journey with support from The Biggest Loser BookThe book guides you through the Express 6-Week Weight Loss Program, which teaches you how to choose high quality foods and follow the 4-3-2-1 Pyramid: four servings of fruits and vegetables, three servings of lean protein, two servings of whole grains, and fewer than 200 calories of extras–whatever foods you want. The Biggest Loser Diet provides meal plans with three smaller meals per day as well as snacks. In addition to meal plans and recipes, you’ll receive the same exercise instructions as the contestants on the show. Exercise is heavily prioritized!! The the book costs between $10 and $15. The second option is spending a week or more at one of the Biggest Loser Resorts.

The program runs in 7-day increments. During this program you will be lead on a weight loss journey by nutrition and exercise experts. You can expect to workout 4-5 times a day, enjoy calorie-controlled meals by professional chefs, and sit in on classes about nutrition, healthy cooking, intuitive eating, and more. A week at one of their resorts ranges anywhere from around $400/ night to $900/night depending on the accommodations you choose. Most guests choose to say for a duration of 14 days, but it’s totally up to you how much time you spend at the resort.


The Biggest Loser Diet, when self-directed, is a super affordable way to get started on your weightloss journey. Additionally, the diet emphasizes healthy, whole foods like vegetables, whole grains, and lean protein—but you’re still allowed to eat from all food groups and you get 200 discretionary calories per day to eat the foods you love.

Their resort program gives you access to an incredibly strong support system. Being completely immersed in a healthy-living program for several days can also be a great way to reset if you fell off track from your health goals.


The 6-week plan outlined by the The Biggest Loser book is pretty regimented. Some users report that meals and workouts cannot be interchanged easily, which can make it difficult to stick to when unexpected events pop up or if you cannot eat certain foods. Calorie limits can also be very low, with some dipping below 1200 calories—a level that may lead to nutrient deficiency in some. The resort option is incredibly expensive and might not be a realistic options for everyone. It also should be noted that while studies have been done on contestants of The Biggest Loser, there haven’t been any rigorous studies done on regular people following the diet. The popularity of the show may also mislead you to have unrealistic expectations of the diet, as contestants of the show are used as success stories in marketing campaigns. The diet and exercise program that you will follow is inherently different from what show contestants go through. Contestants exercise up to eight hours per day and do not deal with the stresses of everyday life that make it more difficult to find time to exercise and cook healthfully.

Why it’s not a top diet

Its long-term efficacy hasn’t been evaluated by experts; so as of now, there is no data to support its capacity for sustainable weight loss and improved health.


Similar to the Atkins Diet, the South Beach Diet is a low carbohydrate diet plan designed to help promote weight loss as well as heart health (it was developed in 2003 by cardiologist Arthur Agatston). The diet focuses on helping you choose healthy fats like those found in nuts and olive oil, lean sources of protein like lean meat, poultry, and seafood, as well as a small amount of healthy, high-fiber carbohydrates with a low glycemic index. You can follow this program by reading the book and preparing your own food throughout, or subscribe to the commercial weight loss plan that includes prepared meals.

The South Beach Diet is split into three phases. In the first two-week phase, which is designed to help you lose between 8 and 13 pounds and eliminate cravings, you’ll eliminate almost all carbohydrates–including fruits, fruit juice, and all starches. If you sign up for the official diet (instead of just following along with the book), you’ll receive 14 days’ worth of healthy prepared meals that focus on lean sources of protein, healthy fats, and high-fiber vegetables. In the second phase, you will still be consuming mostly South Beach Diet prepackaged meals and you will begin adding back in some of the foods you eliminated in Phase 1, like brown rice, whole grains, and low glycemic index fruits. Phase 2 is designed to help you achieve steady weight loss until you reach your goal weight. Every week during the second phase, you’ll receive five days’ worth of prepared meals—giving you the independence to eat what you want for the other two days (South Beach recipes or eating out are equally encouraged). In the final phase, at which point you’ll have reached your goal weight, you can enjoy all foods in moderation while still following the principles of the South Beach Diet (lean proteins, healthy fats, smaller amounts of healthy carbs).


In the first two phases, the South Beach Diet is very simple: you pick from a list of approved foods and meals and that’s it—no grocery shopping, planning, or prepping. This can be especially helpful as you focus on modifying your eating patterns and tuning in to how your body feels when you add carbohydrates back into your diet. While the South Beach Diet doesn’t have any long term clinical studies backing up its efficacy for weight loss, studies have found that eating patterns that focus on vegetables, lean protein, healthy fats, and moderate amounts of whole grain carbs can have beneficial health outcomes.


While the South Beach Diet may lead to moderate weight loss in the beginning due to its low carbohydrate content and strict meal plans, weight loss might plateau as you add in more carbohydrates and are left to cook for yourself. And while it’s very structured in the beginning with the prepared and pre-portioned meals, users might have trouble with the lack of structure in Phases 2 and 3, when it’s up to you to decide how much and which carbohydrates to add back in. Plans can also be costly—up to $460 for 4 weeks of food. And because the diet encourages lots of lean protein, the cost of meats, poultry, and seafood can also add up once you start cooking for yourself. And while the South Beach Diet makes bold claims about its success, there isn’t yet evidence that these claims are effective across populations.

Why it’s not a top diet

There’s not a lot of research backing up the claims of the South Beach Diet with regard to either weight loss or managing diabetes–and experts find that its restrictiveness may make it too difficult to stick to.

The Paleo Diet


The Paleo Diet was developed by Dr. Loren Cordain, an expert on the natural diet of our ancestors during the Stone Age. In response to extensive research on the health benefits of a Stone Age die, he published The Paleo Diet in 2002, detailing what he believed to be the optimal diet and lifestyle for health and longevity. He advocates for a diet rich in lean meats, fish, eggs, fresh fruit, non-starchy vegetables, nuts, seeds, and healthful oils such as olive oil, flaxseed oil, and avocado oil. He also believes that the following foods should be avoided: cereal grains, legumes (including peanuts), dairy, refined sugar, potatoes, processed foods, refined vegetable oils, and added salt. His reasoning is that because our paleolithic ancestors did not have access to these types of foods, our bodies are not well adapted to them. We evolved eating a whole foods diet that was rich in phytonutrients (the nutrients from plants), high quality animal protein, and healthful fats such as omega 3s, all of which are plentiful within The Paleo Diet.


Because this diet is based around whole foods and encourages completely avoiding anything processed, it is likely to lead to weight loss and an overall improvement in health. In fact, several studies have shown that following The Paleo Diet can decrease markers of metabolic syndrome. The Paleo Diet also encourages avoiding many of the foods that commonly cause digestive discomfort or autoimmune-type symptoms (for example: grains, legumes, and dairy). If you suspect that you may have food intolerances The Paleo Diet might be for you. You are also given free reign to eat as much meat as you so desire, provided that you are consuming high quality protein (grass-fed beef, pasture-raised chicken, and wild-caught fish). This makes The Paleo Diet perfect for those who have higher protein requirements or simply enjoy the taste of meat.


This diet is highly restrictive and can be hard to sustain in the long run. Since it doesn’t allow for any processed food, it may require a little more thinking ahead and extra meal prep to make sure that you have Paleo-approved meals and snacks with you throughout the day. Since The Paleo Diet stresses the importance of consuming the highest quality meat and produce, you might find that your grocery bill becomes pretty steep if you are sticking to Dr. Cordain’s guidelines. No one can deny the benefits of eating organic produce and grass-fed beef, but these products are definitely pricey and can take a hit on your wallet. And finally, The Paleo Diet is extremely challenging to follow if you don’t consume meat since all grains and beans (vegetarian protein sources) have been removed.

Why it’s not a top diet

It’s unsustainable and unnecessarily restrictive. In fact, numerous studies have demonstrated the health benefits of consuming many of the foods that are restricted. For example, whole grains are an excellent source of fiber and dairy is a good source of calcium and vitamin D. Additionally, it’s easy to overindulge in high fat, high sugar foods on this diet. Many paleo cookbooks highlight paleo “alternatives” to traditionally non-paleo foods such as paleo banana bread, brownies, and even paleo snickers bars. Because these treats are made with whole foods such a nut butter and dates they are healthier than traditional cookies or candy, but indulging too frequently can result in weight gain. The Paleo Diet also isn’t specifically weight loss diet so it might not yield the results you are looking for if weight loss is your goal.


On paper, Whole30 looks pretty similar to The Paleo Diet—you’ll eliminate all ingredients that weren’t available before our modern industrialized food system. This includes added sugar of any kind, including maple syrup, agave nectar, coconut sugar, Stevia, xylitol, and other artificial sweeteners; alcohol; grains (including corn and rice); legumes; beans; all soy; dairy; and additives like carrageenan, MSG, or sulfites. That leaves a handful of whole, unprocessed foods: meat, seafood, poultry, eggs, vegetables, some fruits, nuts, seeds, and healthy oils. Unlike The Paleo Diet, however, followers are encouraged not to make junk foods or baked goods with the approved ingredients. The diet is designed as a short-term reset or elimination diet, allowing you to see how the foods you were eating and got rid of may have been impacting your health. Proponents of the diet say that many of the forbidden foods wreak havoc on your hormones, disrupt gut health, and promote systemic inflammation, causing symptoms like fatigue, breakouts, mental fogginess, and stomach troubles. The program promises a laundry list of benefits, including improved energy and mental clarity, better athletic performance, better sleep, and a happier disposition. Weight loss actually isn’t a focus: on Whole30, you’re not allowed to weigh yourself.

In terms of cost, you can follow the diet at home using the website or book as a guide, or you can sign up for monthly, quarterly, or annual packages that include the Whole30 Setup, new meal plans each month, and access to recipes.


If you are suffering from any sort of food sensitivity or intolerance, Whole30 can be a great way to determine which foods are causing symptoms (as long as you introduce them back into your diet one at a time instead of all at once on day 31). Whole30 focuses on limiting processed ingredients, which is a great step in the right direction for anyone who wants to start eating healthier. Bonus: you won’t have to count a single calorie or carb on this diet!


The diet seems overly restrictive, even if only for a month. Eliminating entire food groups like dairy, legumes and beans, and grains means that you might miss out on key nutrients like calcium, vitamin D, and B vitamins as well as fiber. And there’s really no reason to ban such foods if they’re not causing you any problems to begin with. Despite thousands of followers claiming that Whole30 “cured” their symptoms or disease—from allergies and asthma to infertility and depression—no studies have investigated such claims. The cost of food can also be prohibitive—even though you’re not paying for prepackaged meals, the reliance on animal proteins can make it expensive.

Why it’s not a top diet

It’s unsustainable and it relies on personal anecdotes and testimonials instead of research and clinical trials to support its claims.

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Addiction and Sleep from <<< Link here

Poor sleep is common in addictions and addiction recovery. Circadian cycles are commonly off sync when you are in recovery, and the poor quality of sleep results in increased chances of relapse. The article below is pasted from Tuck. The link is above. They have a lot of excellent  articles on sleep-related concerns.

Addiction and sleep


Anyone who’s gone through addiction, or cared for a loved one with addiction, knows firsthand the devastating effects it has on a person’s life. Addiction disrupts all areas of your life, and sleep is no exception.

According to one estimate, individuals with addiction are 5 to 10 times more likely to have comorbid sleep disorders.

Sleep and addiction are intricately linked. Many people use alcohol or other drugs to help them fall asleep and treat their insomnia, and accidentally become addicted as a result. Even if one didn’t have sleep problems before their addiction, long-term substance abuse physically changes your brain’s sleep architecture, disrupting your sleep patterns and sleep quality. Then, just as they come to rely on the addiction substance to function during the day, they also can’t sleep without it. Things only get worse in recovery, with sleep problems being one of the longest-lasting symptoms of detox.

Fortunately, there is some hope: addiction, and many of the sleep problems along with it, is treatable. The better you sleep, the lower your risk of relapse. Master your sleep, and it’s much easier to stick to your recovery plan.

If you or a loved one are dealing with addiction and seeking help, please visit the Substance Abuse and Mental Health Services Administration online provider directory or call 800-662-4357 (available toll-free 24/7).

Keep reading to understand how different addictions affect sleep, the common sleep disorders associated with addiction and recovery, and how you can sleep better during recovery.


How Different Addictions Interfere with Sleep

We mentioned in our introduction that certain addictions actually alter one’s sleep architecture. Below we review how different addictions – drug, alcohol, and behavioral – negatively affect sleep.

Sedatives: alcohol and marijuana

Alcohol is a depressant, which leads many people to mistakenly view it as a sleep aid. Between 20 to 30% of Americans with insomnia report turning to alcohol to help them fall asleep.

As a depressant, alcohol does help you fall asleep, but alcohol-induced sleep isn’t restful sleep. Alcoholism or not, people who sleep after a night of drinking increase their risk of nightmares, bedwetting, night sweats, snoring and sleep apnea.

Much of alcohol’s disruption to sleep has to do with how it affects your core body temperature. Your body temperature is just one of the many mechanisms involved in regulating whether you’re asleep or not. In the evening your body temperature begins to drop, making you feel drowsy as your brain releases melatonin. In the morning, your body temperature begins to rise again, waking you up for the day. Alcohol drops your body temperature, which is why it helps you fall asleep, but as the alcohol wears off, your body responds by increasing your temperature, which leads to night sweats and early waking.

Alcoholics also spend less time in REM sleep, the stage of sleep where we dream, process learnings from the day and commit them to memory. Scientists have linked daytime cognitive performance with sufficient REM sleep. Without it, our creativity and mental performance suffer.

alcoholics spend less time in rem sleep

Alcoholics also experience alpha and delta brain waves together – rather than separately, leading to disrupted sleep. Insomnia and sleep deprivation are present throughout alcoholism and recovery.

Like alcohol, marijuana is another substance people often use as a sleep aid. It doesn’t cause early waking like alcohol, but it still interrupts with sleep, decreasing the user’s amount of REM sleep. The effect on REM sleep is so strong that marijuana users who quit are prone to vivid, odd dreams for months afterwards.

Stimulants: cocaine, amphetamines, MDMA and hallucinogens

Stimulants like cocaine, amphetamines, and MDMA are all energizing drugs, so it’s easy to imagine how they interfere with sleep.

Users of these drugs become addicted to the energizing high they create by flooding their brain with dopamine. During their high, they’ll experience insomnia, so energized that it’s tough to fall asleep, followed by periods of hypersomnia during withdrawal.

Just as a night of casually drinking alcohol affects REM sleep, so does a low dose of cocaine. Chronic use of cocaine and ecstasy both reduce REM sleep, causing sleep deprivation that has a noticeable impact on their daytime cognitive performance.

MDMA has a special effect on the brain and sleep architecture because it gradually eats away at the brain’s serotonin levels. Since serotonin is part of the melatonin production process, ecstasy users experience sleep deprivation symptoms sooner than users of other types of drugs, especially in regards to their cognitive performance (“Percent Correct” in the chart below on the left) and impulsivity:

decline in cognitive performance among mdma users associated with sleep deprivationimpulsivity score among sleep deprived mdma users
Even once they’ve gone through recovery, especially heavy MDMA users display apparently permanent changes to their sleep architecture. Heavy users of cocaine and amphetamines also appear to permanently alter their circadian rhythms and may experience disrupted sleep forever.  Additionally, cocaine withdrawal is associated with nightmares as well.


Our bodies are not equipped to handle intense levels of pain on our own, which is why opioids like methadone, oxycodone, and hydrocodone are available in prescription form. These drugs help individuals cope with the severe or chronic pain associated with surgery, cancer, or other health procedures and issues. Opioids work by attaching to the dopamine receptors in your brain, enabling your brain to better handle the pain.

Unfortunately, when abused – or not used as directed – opioids create a similar euphoric effect to cocaine, due to the way they interact with your dopamine receptors. If a person continues to abuse opioids, the more reliant they become on them in order to deal with even lesser amounts of pain. This results in addiction.

Like the other addictions on this list, opioid abusers experience less REM sleep. Their REM sleep is cut in half, as is their deep sleep (the stage of sleep where your body repairs and restores your muscles and body tissue). More of their time is spent in light sleep, which, while important, is much less restorative. They also get less sleep overall, and incur an increased risk for central sleep apnea.

All these effects combine to cause sleep deprivation that affects opioid addicts mentally and physically during the day, worsening their memory and their tolerance for pain. Even without abuse, chronic as-prescribed use of opioids interferes with your sleep architecture to such an extent that it causes fatigue.

Like most forms of addiction, opioid withdrawal is intense, but opioid addicts in particular are at increased risk for restless legs syndrome (RLS).

Sleep medication

Like opioids, prescription sleep medications like Ambien, Sonata, and Lunesta are another common and legal form of medication people become addicted to. Because it’s a legal drug, sleep medications seems safe, so people take liberties with their dosage without consulting their doctor first. They may increase their dosage or take it more often than prescribed, increasing their risk for addiction.

Like a glass of wine before bed, people think nothing of taking sleep medication before sleep. However, these drugs are not approved or intended for long-term use. Unfortunately, the more often people take them, the more likely they are to come to rely on them to fall asleep just as opioid abusers need their drugs to manage their pain.

The moment they have trouble falling asleep, people go straight back to sleep medication instead of trying other behavioral methods. This results in overuse and abuse of the medication that’s especially dangerous and associated with a tripled mortality risk, cancer, and driving while asleep.

Behavioral addictions

Behavioral addictions like gambling and internet may not initially have the devastating physical effects of other drugs, but they do interfere with sleep and worsen one’s emotional and mental health. When you consider the correlation of poor mental health with outcomes like suicide, the physical risk becomes clear.

Addictive gamblers and internet users alike are at increased risk for anxiety and mood disorders that often cause, co-exist with, or contribute to insomnia. The worse their sleep, the worse they feel about their addiction – fueling a vicious cycle.

For example, studies of college-aged smartphone addicts show a direct relationshipbetween high smartphone use and depression, anxiety, sleep problems, and associated daytime dysfunction. The sleep deprivation caused by behavioral addictions like internet addiction leads to depression and a significant increase in suicide attempts:

suicide risk increases with sleep problems in internet addicts


You probably noticed a common theme as you read the above section. Across the board, addictions reduce REM sleep, which is a problem in itself. However, many addictions are associated with specific sleep disorders as well.

While many people turn to alcohol, drugs, and other substances to help them sleep in the first place, these addictions exacerbate existing sleep problems and cause new ones of their own. Sleep problems caused by the addiction are known as substance-induced sleep disorders.

Substance-induced sleep disorders include:

  • Insomnia: Chronic insomnia describes regular difficulty falling or staying asleep, perhaps waking up too early or multiple times during the night. Insomnia is an extremely common symptom of both addiction and recovery, for sedatives, stimulants, prescription drugs, and behavioral addictions alike.
  • Hypersomnia: Hypersomnia describes excessive daytime sleepiness, or a lack of feeling unrefreshed from sleep. Often, it occurs with insomnia. People who can’t fall asleep tend to demonstrate symptoms of hypersomnia as well, frequently oversleeping or falling asleep during the day.
  • Parasomnias: This is a catch-all for abnormal sleep behaviors, such as sleepwalking or night terrors. Parasomnias are a common experience of hallucinogen abuse, and may create further insomnia, as individuals become afraid to fall asleep and experience the behavior. Nightmares are a frequent occurrence for those in marijuana or cocaine withdrawal.
  • Sleep apnea: Sleep apnea is a form of sleep-disordered breathing where the individual stops breathing momentarily during sleep. It may be caused by a relaxation of the throat muscles (as occurs with alcohol abuse and obstructive sleep apnea), or from a miscommunication with the brain (as with opioid addicts and central sleep apnea). The brain has to “wake up” in order to get you start breathing again, reducing the quality of your sleep even if you don’t remember waking up. Sleep apnea is experienced by over half of people with addiction.
  • Restless legs syndrome (RLS): RLS is a disorder where individuals experience an uncomfortable sensation in their lower limbs that can only be relieved by moving them. It typically occurs when the individual is lying down, as one is when you’re lying in bed. The constant need to move the legs in order to calm the sensation makes it difficult to relax sufficiently to fall asleep. RLS affects a third of addicts and is particularly common among opioid addicts.

Sleep deprivation

Each one of these sleep issues contributes to the sleep deprivation that makes one more reliant on their addiction to sleep, focus, or just feel okay – and makes it that much harder to stick to a detox plan.

Whether they’re not getting enough sleep overall, or the sleep they’re getting is just lower quality, people experience the same effects of sleep deprivation. These include difficulty focusing, trouble remembering things, poor decision-making, emotional volatility, decreased reaction time, and in the long-term, increased risk for cancer, diabetes, and heart disease.

Sleep deprivation is often linked with substance abuse, as both a symptom and a cause. Among adolescents, poor sleep is itself a predictor for marijuana and cigarette use. Chronic sleep deprivation reduces your dopamine, and since addicts may already be damaging their dopamine receptors, this makes them even more dependent on their addiction to regulate their emotions and response to pain.


Sleep Problems During Addiction Recovery

The beginning stages of detox are rough for all types of addiction. The first few days to a week see physical symptoms that are extremely uncomfortable, such as shakes or tremors, fever, vomiting, and headaches. Emotional symptoms understandably accompany these, including poor mood, depression, anxiety, and irritability.

Symptoms vary by individual, addiction, and the severity of their addiction. For instance, some people withdrawing from sleep medication may experience seizures, and 5% of alcoholics may experience delirium tremens (DTs). DTs describe a group of additional symptoms such as hallucinations, heavy sweating, and increased heart rate.

Because symptoms can vary, it is important to seek medical help and guidance as you begin recovery. While some can succeed with a cold turkey approach, for others it can be dangerous. Individuals with addictions to opioid and sleep medications are often advised to go slowly and taper their dosage down to minimize the severity of withdrawal symptoms and reduce their risk for relapse.

By the end of your first week of detox, most of the physical symptoms either disappear or significantly decrease in severity. Remaining symptoms will continue to gradually diminish in the following months.

Insomnia during detox

However, one pesky symptom that stays ever present seems to be sleep problems. Insomnia is one of the most common, and persistent, symptoms of withdrawal. Between one to three-quarters of people in detox experience insomnia.

Insomnia is challenging enough to deal with when you’re not in detox. As we noted above, it’s so challenging that it’s what drives many people to sedative drugs and alcohol in the first place. When you’re in withdrawal, however, you’re experiencing a variety of uncomfortable symptoms, sensations, and feelings that you haven’t encountered before – and you’re having to face them without the crutch that got you by before.

Many of the drugs we described above, such as cocaine, ecstasy, opioids, and amphetamines, upset your brain’s dopamine production. During your addiction, your brain became used to a new level of “normal” – which relied on those drugs to help you deal with pain and stay balanced emotionally. During the first few weeks of withdrawal, your brain slowly stabilizes back to normal dopamine production. While that’s happening, however, physical pain and negative emotions like stress and anxiety are much harder to bear.

It’s not just physical, either. People who drank or smoked marijuana before bed trained their mind to recognize those activities to precursors to sleep. Without them, your brain is suddenly left wondering when it’s time to go to bed.

Meanwhile, you’re running on less or poor quality sleep thanks to your detox-induced insomnia. This causes sleep deprivation that further reduces your tolerance for pain, and makes you quick to lash out at others or get irritable.

Insomnia is one of the biggest predictors of relapse, and the risk is doubled for those who develop a sleep disorder. This is why experts recommend that individuals include sleep as part of the treatment plan. Research shows that treating insomnia improves both sleep quality and symptoms of depression in those with alcoholism.

Depending on the severity of your addiction, sleep problems associated with recovery can last for years. Fortunately, once you start sleeping better consistently, you can take it as evidence that you’ve fully detoxed.


Tips for Improving Sleep During Addiction Recovery

One of the best things you can do to ease the uncomfortable symptoms of recovery and ensure your ultimate success is to get good sleep. Of course, that’s easier said than done.

Follow these tips to get better sleep during addiction recovery.

1. Get help from others.

It takes a village to recover from addiction. Open yourself up to others and ask them for help during this difficult time. Your loved ones care about you and want you to succeed; chances are they will be happy to help. Ask if you can spend the night with them during rough periods, or coordinate times for them to check in on you and see if you need anything.

Consider joining local support groups, too. Speaking with others who have gone through addiction recovery, or are currently going through it  like yourself, can be helpful because they understand just how you feel. This website lists resources for various addictions, including 12-step groups, online forums, and treatment center locator tools.

2. Try cognitive behavioral therapy.

You round out your support system further with professional therapy and medical help. and SAMHSA both offer online directories to help you find treatment centers and health professionals who specialize in treating your addiction.

Cognitive behavioral therapy in particular may be helpful. It’s a psychotherapy technique that involves 6 to 12 sessions. A therapist works with the patient to help them recognize the negative thoughts and behavioral patterns contributing to their problem. CBT treats a variety of issues ranging from addiction to mood disorders and insomnia.

CBT-I is a subset focused specifically treating insomnia. In CBT-I, therapists work with individuals to educate them about sleep hygiene (more on this in the next tip), adjusting their sleep environment to promote sleep instead of prevent it (more on this in the tip after that), and practice different therapies such as relaxation exercises to induce sleep, sleep restriction to retrain the body to follow a specific sleep schedule, and more.


3. Improve your sleep hygiene.

Sleep hygiene describes the behaviors and thoughts you have around sleep. Having good sleep hygiene is often as simple as learning what it is, and adjusting your behaviors accordingly.

For instance, good sleep hygiene includes following a regular sleep schedule, keeping your bedroom cool and dark, not eating or exercising before bed, avoiding alcohol or caffeine later in the day, and turning off your electronics before bed. Electronics energize the mind, flooding your retinas with strong blue light that tricks your brain into thinking it’s daytime and time to be up and awake.

4. Turn your bedroom into a sleep-promoting environment.

Devote your bedroom to sleep and sex only – this trains your mind to associate it as a place of relaxation only. Avoid doing work or hobbies in your bedroom.

Make this goal easier to achieve by removing stressful clutter, work items like a computer or desk, and even fun distractions like a TV from your bedroom.

Invest in a comfortable mattress that feels great to sleep on. Keep your bedroom dark and cool with blackout curtains. Force your mind to focus on sleep alone with eye masks that block out light and white noise machines that drown out the noise.

If you have difficulty falling asleep due to the feelings of anxiety that accompany the recovery process, try keeping a diary. You can write your thoughts down in there, freeing them from your mind so you can focus on sleep and leave your worries for another day.

5. Follow a regular sleep schedule.

Set a regular sleep schedule and follow it daily, even on weekends. You want to train your mind to naturally tire and wake up at the same time each day. Sticking to a schedule makes it easier to stick to other parts of your treatment plan.

Avoid taking naps if possible, but if you absolutely must, limit them to 30 minutes and don’t take them past the afternoon. Otherwise, it will only be harder to fall asleep that night.

Consider pairing your sleep schedule with a nightly bedtime routine. In the 30 minutes before bed each night, follow the same set of calming activities to teach your brain that it’s time for sleep. You might practice meditation, read a book, or listen to some relaxing music.

6. Try bright light therapy.

Bright light therapy involves sitting in front of an artificial light box that’s specially designed to mimic the strength of sunlight without the UV rays.

Exposure to this light in the morning helps reset your circadian rhythms and can offset the fatigue of sleep deprivation and hypersomnia.

Alternately, boost your energy levels by getting lots of natural sunlight. Go for a walk in the morning outside, or position your work desk to be by a window.

7. Watch your diet and exercise.

Speaking of walking, exercise is a great way to get out excess energy and physically tire your body in preparation for sleep later that night. Just be sure to do it in the earlier part of the day, or you’ll be energized to go for another run when you need to be falling asleep.

Watch what you eat as well. Avoid heavy meals before bed, and try to eat healthy generally. Healthier foods promote better mood and better sleep. Limit your caffeine intake, and satisfy your thirst with water instead.

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Revisiting the Hallucinogenic Potential of Ketamine



A Case Built on Current Research Findings

Ketamine has caused quite a stir in psychiatric practice. Sub-anesthetic administrations of ketamine have been shown to markedly improve symptoms of depression and anxiety.1 While the growing off-label use of ketamine speaks to the need for novel approaches to psychiatric care and treatment-resistant illness, it also presents an ethical dilemma, wherein widespread adoption has once again leaped ahead of scientific understanding.

The current literature suggests that therapeutic effects of ketamine involve modulation of glutamate neurotransmission, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor potentiation, downstream influences on neurotrophic signaling cascades and neuroplasticity, and functional changes in assorted neural networks. Additional work is necessary to clarify the importance and reliability of these biological findings.

Another arc to the ketamine story dates back to a decades-old era of psychedelic research and search for medications with transformative power. Indeed, although primarily conceptualized today as a dissociative anesthetic, ketamine has also been classified more broadly as a hallucinogen. Hallucinogens function by various pharmacological mechanisms of action but exhibit similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes.

Current biological theories involving ketamine’s antidepressant effect may be inseparable from these non-ordinary experiences of consciousness, but we can only know the answers to questions we ask. Here we examine findings from contemporary research that hint at the unexplored hallucinogenic potential of ketamine and considerations for future investigation.

There has been a resurgence of interest in hallucinogenic psychedelics (eg, psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-Dimethyltryptamine (DMT)) and entactogens (eg, 3, 4-methylenedioxymethamphetamine [MDMA]) in psychiatric research, which are hypothesized to achieve clinical benefit due to, in part, experiences of altered consciousness and fundamental shifts in mental frameworks.2

These drugs have been associated with cognitive states of enduring personal importance and have been compared with mystical experiences that might emerge over the ordinary course of life and carry sacred or spiritual meaning. Furthermore, these experiences may powerfully influence existential concepts of self, including moral values, self-identity, and purpose. There is converging evidence that these psychedelic effects are mediated in part by activity at 5HT-2A receptors. Ketamine may induce alterations in consciousness and personal frameworks similar to those achieved by serotonergic psychedelics while also sharing a common glutamatergic pathway of drug effect.3,4 However, there has been little investigation into how such changes might mediate the therapeutic potential of ketamine.

Preliminary data suggest that ketamine produces meaningful, transformative experiences that may help patients accept healthier values, behaviors, and beliefs related to abstinence from drugs and alcohol.5,6 Other evidence suggests that dose-related mystical-type experiences mediate the effects of ketamine on motivation to quit in cocaine-dependent research volunteers.7Few recent studies have examined whether ketamine’s hallucinogenic properties are implicated in antidepressant effects; however, psychiatric vulnerabilities to depression plausibly involve an existential dimension. This dimension includes depressive symptoms of hopelessness, guilt, and suicidality, which appear to be ketamine-sensitive.8

The evidence

Given the paucity of modern literature exploring the psychedelic and mystical properties of ketamine in depression, more widespread data on psychotomimetic and dissociative effects of ketamine provide some initial groundwork. Berman and collegeagues9 and Zarate and colleagues10 suggested that the antidepressant effects of ketamine (0.5 mg/kg over 40 min) were disconnected from ketamine-induced psychotomimetic symptoms. The antidepressant effects, measured by the Hamilton Depression Rating Scale (HDRS), were significant even after positive symptoms on the Brief Psychiatric Rating Scale (BPRS) returned to baseline. However, it was also noted that initial changes in BPRS positive symptom scales from baseline trended to predict a greater decrease in HDRS scores within a day of treatment with ketamine.

A small study further demonstrated a substantial relationship between psychotomimetic effects 30 minutes after ketamine administration (0.54mg/kg over 30 min) as measured by BPRS and antidepressant effects in the following week.11 A larger study involving 108 patients found that dissociation measured by the Clinician Administered Dissociative States Scale (CADDS) at 40 minutes was associated with HDRS score improvement at 230 minutes and 7 days after infusion.12 Although no relationship between initial BPRS positive subscale scores and antidepressant effect was found, a correlation between CADSS and BPRS scores was found at 40 minutes postinfusion.

In a small study by Valentine and colleagues,13 the proposed correlation between ketamine-induced dissociation and antidepressant efficacy was not observed. However, a larger analysis found that greater intra-infusion dissociation as measured by CADDS was one of the strongest predictors of extended antidepressant response.14 Both of these studies utilized a single 0.5 mg/kg ketamine infusion delivered over 40 minutes.

Further investigation is needed, but there is an emerging rationale for a connection between the psychotomimetic or dissociative effects of ketamine and its antidepressant efficacy. Perhaps the experience of these effects simply un-blinds patients as to whether they are receiving ketamine or placebo in randomized trials; it may also be that such symptoms are only a “side effect” of ketamine’s mechanism of action. However, it is also worth considering that the psychotomimetic or dissociative effects associated with ketamine treatment are markers or mediators of subjective experiences of potential therapeutic value seen with other hallucinogenic agents.

Recommended dosing

The recommended doses of ketamine for anesthetic induction are typically 1 to 4.5mg/kg IV and 6.5 to 13 mg/kg IM, with alternate, off-label recommendations for 0.5 to 2 mg/kg IV and 4 to 10 mg/kg IM, primarily in the context of adjuvant drug use. For use in depression, ketamine is most commonly administered at a sub-anesthetic dose of 0.5mg/kg IV across 40 minutes.

Interestingly, in a study of electroconvulsive therapy (ECT) and anesthetic induction with either a near-anesthetic dose of IV ketamine (0.8mg/kg) alone, sub-anesthetic ketamine (0.5mg/kg) plus propofol (0.8mg/kg), or propofol alone (0.8mg/kg), predicted a more rapid antidepressant effect and a higher remission rate than propofol use. The near-anesthetic dose of ketamine was associated with superior antidepressant effects than the mixed, sub-anesthetic dose.15

In a study of ketamine alongside psychotherapy for heroin addiction, Krupitsky and colleagues6compared the effects of 2 doses of ketamine (0.2 and 2.0 mg/kg IM) and found that only the higher dose was associated with a “full psychedelic experience” as measured by the Hallucinogen Rating Scale (HRS). The lower dose was considered a “sub-psychedelic” active placebo, but was nonetheless associated with some positive drug effects: patients were still affected by their experiences and considered them useful and therapeutic. The high dose group ultimately experienced higher rates of abstinence, greater effect on emotional attitudes related to abstinence, and lower rates of relapse and drug craving than the low dose group. Both doses resulted in post-treatment reductions in measures of depression and anxiety; there were no significant differences between the groups.

Similarly, Dakwar and colleagues7 compared the effects of 0.41 mg/kg and 0.71 mg/kg doses of IV ketamine given to cocaine-dependent patients. Dose-dependent mystical-type effects as measured by Hood’s Mysticism Scale (HMS) were seen as well as a relationship between HMS scores and the motivation to quit cocaine 24 hours post-infusion.

A different study involving a lower dose of intramuscular (IM) ketamine did not generate the same mystical-type phenomena.16 Perhaps these results highlight the importance of calibrating dosing and delivery. Clements and colleagues17 demonstrated that ketamine had reduced bioavailability with IM administration compared with IV administration. Taken together, these findings support the idea that positive treatment outcomes for ketamine may be dose-dependent and its psychoactive effects are based on delivery parameters.


One criticism of ketamine has been its short duration of antidepressant effect, with benefits peaking at 24 hours post-infusion and generally subsiding by 72 hours. The most promising approach to this challenge thus far seems to be the strategy of repeated-dose ketamine infusions, which have observed extended time-to-relapse and increased rates of antidepressant response.18

If ketamine’s therapeutic effect is indeed mediated by psychoactive experience, it may be that repeated dosing of ketamine improves outcomes by increasing opportunities for personally meaningful events to occur. One caveat is that some studies have shown repeated dosing to be associated with fewer dissociative symptoms over time—at first glance this suggests that the antidepressant value of serial ketamine administration might be independent of hallucinogenic effects.

While this requires further investigation, it is also important to consider other interpretations of that evidence: that acclimation to altered states of consciousness may contribute to recall bias, that experimental protocols that frame dissociative symptoms as a “side effect” or “adverse event” may lead to underreporting if overall patient experiences of ketamine are positive, or even that the benefit of repeated dosing may be less related to cumulative drug effect than other factors, such as repeated interactions with care providers or increased opportunities for reflection and synthesis.

One study of repeated infusions demonstrated that antidepressant response very early in the course of treatment strongly predicted subsequent response; conversely, a lack of rapid response was a poor prognostic indicator for improvement after additional infusions. Whether positive early responses to ketamine are mediated by psychological factors, biological susceptibility, or both: it is necessary to clarify these factors in shaping sustainable strategies for treatment.

A cautious approach also seems imperative given evidence that ketamine demonstrates agonist activity at μ-opioid receptors and dopaminergic effects that may confer acute relief of depressive symptoms but also greater risk for positive drug reinforcement and dependence. With further insight into psychological responses mediated by ketamine, it may be that a therapy-based framework for ketamine administration optimizes treatment efficacy and sustainability, while also minimizing unnecessary drug exposure, adverse effects of chronic use, and dependency risk.

Further study needed

In one study, long-term abstinence in persons who were substance dependent was achieved with Ketamine Psychedelic Therapy (KPT), which incorporates 1 or 2 sessions of ketamine-facilitated existential reappraisal into an existential psychotherapy.6 Additional exploration would be needed to determine which therapeutic approaches most beneficially augment ketamine treatment and minimize risks for harm. Nevertheless, a more holistic approach to ketamine as a treatment modality may be better suited to recreate the marked, persistent effects of MDMA in patients with PTSD. For example, in one study sustained symptom reductions were achieved with 12 weeks of psychotherapy but with limited MDMA exposures of only three 8-hour sessions.19

Another area that requires further investigation is how a patient’s past history might shape psychoactive responses. These personal and quite variable histories have been explored for some hallucinogenic agents but minimally for ketamine. The expectations and personal experiences of the individual user along with the external environment of use have been identified as critical factors in influencing subjective drug effects—coined “set” and “setting,” respectively—and are now considered well-established elements of human hallucinogen research.20

Therapies aimed at the pharmacological production of a transformative experience may depend on factors such as patient personality structure, preparation for treatment, emotional activation before drug intake, treatment context, and perceived quality of the experience. Given the unique psychological risks of hallucinogen administration, it is recommended that clinicians screen for personal or family histories of psychotic or other severe psychiatric disorders prior to treatment. Clinicians are also encouraged to facilitate careful patient preparation for sessions, provide a safe physical environment for treatment administration, and allow for interpersonal support during sessions. These and other insights from hallucinogenic research might valuably inform treatment protocols for ketamine administration.

Ketamine is uniquely poised to make a tremendous impact on psychiatric care, even redefining boundaries for patients with variations in depressive disorders that were once thought to be “treatment resistant.” Our synthesis of this emerging and old literature points to the unexplored hallucinogenic potential of ketamine. By further understanding the desirable psychoactive effects of ketamine, clinicians can build on initial treatment successes and maximize patient successes.

Future directions for research include:

• Further investigating the relationship between ketamine-induced psychotomimetic and dissociative effects and treatment efficacy

• Clarifying the connection between these effects and potentially desirable hallucinogenic experiences

• Exploring the therapeutic value of such elicited experiences

• Revisiting dosing strategies that account for existential phenomena and looking beyond dissociation as simply being an “adverse event”

• Incorporating psychotherapy-based frameworks into ongoing investigation

• Assessing set and setting factors that may shape treatment responses

Some answers and clues are likely to be found in the forgotten works of older psychedelic research. Agents like ketamine can exert their greatest therapeutic effect in the afterglow of profound alterations of consciousness, revealing a propensity for growth and healing that has not been evident to the suffering, depressed patient. Wherever the journey takes us, it is exactly the right time to bring together all the strands—brain and mind, old and new, caution and thrill—in assembling the unfinished story of ketamine.



1. Feifel D. Breaking sad: unleashing the breakthrough potential of ketamine’s rapid antidepressant effects. Drug Dev Res. 2016;77;489-494.

2. Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacol (Berl). 2006;187:268-283, 292.

3. Perry EB, Cramer JA, Cho HS, et al. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacol (Berl). 2007;192:253-260.

4. Vollenweider FX, Kometer M. The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nat Rev Neurosci. 2010;11:642-651.

5. Jansen KLR. Ketamine: Dreams and Realities. Sarasota, FL: Multidisciplinary Association for Psychedelic Studies; 2001.

6. Krupitsky E, Burakov A, Romanova T, et al. Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. J Subst Abuse Treat. 2002;23:273-283.

7. Dakwar E, Levin F, Foltin RW, et al. The effects of sub-anesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine dependent research volunteers. Biol Psychiatry. 2014;76:40-46.

8. Mathew SJ, Shah A, Lapidus K, et al. Ketamine for treatment-resistant unipolar depression: current evidence. CNS Drugs. 2012;26:189-204.

9. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351-354.

10. Zarate CA, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856-864.

11. Sos P, Kirova M, Novak T, et al. Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression. Neuro Endocrinol Lett. 2013;34:287-293.

12. Luckenbaugh DA, Niciu MJ, Ionescu DF, et al. Do the dissociative side effects of ketamine mediate its antidepressant effects? J Affect Disord. 2014;159:56-61.

13. Valentine GW, Mason GF, Gomez R, et al. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res. 2011;191:122-127.

14. Pennybaker SJ, Niciu MJ, Luckenbaugh DA, Zarate CA. Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion. J Affect Disord. 2017;208:560-566.

15. Zhong X, He H, Zhang C, et al. Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression. J Affect Disord. 2016;201:124-130.

16. Lofwall MR, Griffiths RR, Mintzer MZ. Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults. Exp Clin Psychopharmacol. 2006;14:439-449.

17. Clements JA, Nimmo WS, Grant IS. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. J Pharma Sci. 1982;71:539-542.

18. Murrough JW, Perez AM, Pillemer S, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013;74:250-256.

19. Mithoefer, M. C. et al. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol. 2013;27:28-39.

20. Leary T, Litwin GH, Metzner R. Reactions to psilocybin administered in a supportive environment. J Nerv Ment Dis. 1963;137:561-573.

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The drug Ketamine is considered a breakthrough treatment for depression and some other neuropsychiatric conditions. Below are excerpts from recent articles discussing this revolutionary treatment and the links to the full articles.

Ketamine For Depression: the Highs and Lows.

The Lancet Psychiatry. VOLUME 2, ISSUE 9, P783–784, SEPTEMBER 2015

Long used as an anaesthetic and analgesic, most people familiar with ketamine know of it for this purpose. Others know it as a party drug that can give users an out-of-body experience, leaving them completely disconnected from reality. Less well known is its growing off-label use in the USA for depression, in many cases when other options have been exhausted.

David Feifel, a professor of psychiatry at the University of California, San Diego, was one of the first clinicians to use ketamine off-label to treat depression at UCDS’s Center for Advanced Treatment of Mood and Anxiety Disorders, which he recently founded. “Currently approved medications for depression all have about the same, very limited efficacy. A large percentage of patients with depression do not get an adequate level of relief from these antidepressants even when they have tried several different ones and even when other drugs known to augment their effects are added to them”, Feifel tells The Lancet Psychiatry. “The stagnation in current antidepressant medication on the one hand, and the tremendous number of treatment-resistant patients, has propelled me to explore truly novel treatments like ketamine.”

Compelling published study results and case reports exist of patients’ depression—in some cases deeply entrenched depression that has lasted months or even years—alleviating within hours of use of ketamine. However, critics have warned that the drug has not been studied sufficiently (at least outside clinical trials), and also emphasized the cost. Patients can pay more than $1000 per session for treatment that must usually be repeated several times. That cost is rarely covered by the patient’s medical insurance.

Advocates of ketamine use in depression are excited because it has a different mechanism of action to standard antidepressants, which affect signalling by monoamine neurotransmitters such as serotonin, noradrenaline, or dopamine. Ketamine is thought to act by blocking N-methyl-d-aspartate (NMDA) receptors in the brain, which interact with the amino acid neurotransmitter glutamate.

Feifel states that he has patients who have been receiving ketamine treatments every 2–4 weeks for long periods, some for around 3 years, and has not yet seen any safety issues arise.

Pharmaceutical companies are entering this exciting arena by attempting to develop new drugs based on ketamine without similar side-effects. Feifel dismisses the notion that the dissociative so-called trip induced by ketamine is actually an important negative side-effect. “Although I have had a couple patients have unpleasant ‘trips’, it’s exceedingly rare, usually dose related, and very transitory due to ketamine’s rapid metabolism.” Feifel says that, more often than not, patients find the trip to be positive, or even spiritual, and believe it is an important component of the antidepressant effect they experience afterwards. “There is no doubt the dissociative effect represents a logistical issue, requiring monitoring—and this should be addressed in any approval given for ketamine”, he adds.

Feifel says that it is not for him, but for his patients to decide where the balance of risks and benefits lies in trying ketamine to treat their depression”One could make a compelling argument that it’s unethical to withhold ketamine treatments from someone who has chronic, severe treatment resistant depression. But I know this from the patients who tell me they would not be in this world right now if it were not for the ketamine.”

Feifel concludes that it is straightforward to talk to TRD patients about ketamine. “I tell them all the relevant information. The efficacy rates, time to onset of benefits, duration limitations, alternatives, lack of insurance coverage, and other information. My job is to make sure they understand the parameters of the treatment, not to decide whether they should do it.”

Full article: The Lancet

Ketamine for depression the highs and lows b

Onetime Party Drug Hailed as Miracle for Treating Severe Depression

Washington Post, Feb 2, 2016

Ketamine, popularly known as the psychedelic club drug Special K, has been around since the early 1960s. It is a staple anesthetic in emergency rooms, regularly used for children when they come in with broken bones and dislocated shoulders. It’s an important tool in burn centers and veterinary medicine, as well as a notorious date-rape drug, known for its power to quickly numb and render someone immobile. Since 2006, dozens of studies have reported that it can also reverse the kind of severe depression that traditional antidepressants often don’t touch.

Experts are calling it the most significant advance in mental health in more than half a century. They point to studies showing ketamine not only produces a rapid and robust antidepressant effect; it also puts a quick end to suicidal thinking.  “This is the next big thing in psychiatry,” says L. Alison McInnes, a San Francisco psychiatrist who over the past year has enrolled 58 severely depressed patients in Kaiser’s San Francisco clinic. The excitement stems from the fact that it’s working for patients who have spent years cycling through antidepressants, mood stabilizers and various therapies. “Psychiatry has run out of gas” in trying to help depressed patients for whom nothing has worked, she says. “There is a significant number of people who don’t respond to antidepressants, and we’ve had nothing to offer them other than cognitive behavior therapy, electroshock therapy and transcranial stimulation.”

Ketamine does, however, have one major limitation: Its relief is temporary. Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion.

A study published in the journal Science in 2010 suggested that ketamine restores brain function through a process called synaptogenesis. Scientists at Yale University found that ketamine not only improved depression-like behavior in rats but also promoted the growth of new synaptic connections between neurons in the brain.

Patients often describe a kind of lucid dreaming or dissociative state in which they lose track of time and feel separated from their bodies. Many enjoy it; some don’t. But studies at NIMH and elsewhere suggest that the psychedelic experience may play a small but significant role in the drug’s efficacy.

As a drug once known almost exclusively to anesthesiologists, ketamine now falls into a gray zone. As the use of ketamine looks likely to grow, many psychiatrists say that use of ketamine for depression should be left to them. “The bottom line is you’re treating depression,” says psychiatrist David Feifel, director of the Center for Advanced Treatment of Mood and Anxiety Disorders at the University of California at San Diego. “And this isn’t garden-variety depression. The people coming in for ketamine are people who have the toughest, potentially most dangerous depressions. I think it’s a disaster if anesthesiologists feel competent to monitor these patients.”

Full article: The Washington Post

Onetime party drug hailed as miracle for treating severe depression

A Ketamine intravenous drip being prepared. (Amarett Jans/Courtesy of Enrique Abreu)

February 1, 2016

It was November 2012 when Dennis Hartman, a Seattle business executive, managed to pull himself out of bed, force himself to shower for the first time in days and board a plane that would carry him across the country to a clinical trial at the National Institute of Mental Health (NIMH) in Bethesda.

After a lifetime of profound depression, 25 years of therapy and cycling through 18 antidepressants and mood stabilizers, Hartman, then 46, had settled on a date and a plan to end it all. The clinical trial would be his last attempt at salvation.

For 40 minutes, he sat in a hospital room as an IV drip delivered ketamine through his system. Several more hours passed before it occurred to him that all his thoughts of suicide had evaporated.

“My life will always be divided into the time before that first infusion and the time after,” Hartman says today. “That sense of suffering and pain draining away. I was bewildered by the absence of pain.”

Ketamine could be speedy depression treatment

Ketamine is being used by researchers at The National Institutes of Health as a treatment for major depression. 

Ketamine, popularly known as the psychedelic club drug Special K, has been around since the early 1960s. It is a staple anesthetic in emergency rooms, regularly used for children when they come in with broken bones and dislocated shoulders. It’s an important tool in burn centers and veterinary medicine, as well as a notorious date-rape drug, known for its power to quickly numb and render someone immobile.

Since 2006, dozens of studies have reported that it can also reverse the kind of severe depression that traditional antidepressants often don’t touch. The momentum behind the drug has now reached the American Psychiatric Association, which, according to members of a ketamine task force, seems headed toward a tacit endorsement of the drug for treatment-resistant depression.

Experts are calling it the most significant advance in mental health in more than half a century. They point to studies showing ketamine not only produces a rapid and robust antidepressant effect; it also puts a quick end to suicidal thinking.

Traditional antidepressants and mood stabilizers, by comparison, can take weeks or months to work. In 2010, a major study published in JAMA, the journal of the American Medical Association, reported that drugs in a leading class of antidepressants were no better than placebos for most depression.

A growing number of academic medical centers, including Yale University, the University of California at San Diego, the Mayo Clinic and the Cleveland Clinic, have begun offering ketamine treatments off-label for severe depression, as has Kaiser Permanente in Northern California.

The ‘next big thing’

“This is the next big thing in psychiatry,” says L. Alison McInnes, a San Francisco psychiatrist who over the past year has enrolled 58 severely depressed patients in Kaiser’s San Francisco clinic. She says her long-term success rate of 60 percent for people with treatment-resistant depression who try the drug has persuaded Kaiser to expand treatment to two other clinics in the Bay Area. The excitement stems from the fact that it’s working for patients who have spent years cycling through antidepressants, mood stabilizers and various therapies.

“Psychiatry has run out of gas” in trying to help depressed patients for whom nothing has worked, she says. “There is a significant number of people who don’t respond to antidepressants, and we’ve had nothing to offer them other than cognitive behavior therapy, electroshock therapy and transcranial stimulation.”

McInnes is a member of the APA’s ketamine task force, assigned to codify the protocol for how and when the drug will be given. She says she expects the APA to support the use of ketamine treatment early this year.

The guidelines, which follow the protocol used in the NIMH clinical trial involving Hartman, call for six IV drips over a two-week period. The dosage is very low, about a tenth of the amount used in anesthesia. And when it works, it does so within minutes or hours.

“It’s not subtle,” says Enrique Abreu, a Portland, Ore., anesthesiologist who began treating depressed patients with it in 2012. “It’s really obvious if it’s going to be effective.

“And the response rate is unbelievable. This drug is 75 percent effective, which means that three-quarters of my patients do well. Nothing in medicine has those kind of numbers.”

So far, there is no evidence of addiction at the low dose in which infusions are delivered. Ketamine does, however, have one major limitation: Its relief is temporary. Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion.

Ketamine works differently from traditional antidepressants, which target the brain’s serotonin and noradrenalin systems. It blocks N-methyl-D-aspartate (NMDA), a receptor in the brain that is activated by glutamate, a neurotransmitter.

In excessive quantities, glutamate becomes an excitotoxin, meaning that it overstimulates brain cells.

“Ketamine almost certainly modifies the function of synapses and circuits, turning certain circuits on and off,” explains Carlos Zarate Jr., NIMH’s chief of neurobiology and treatment of mood disorders, who has led the research on ketamine. “The result is a rapid antidepressant effect.”

Rapid effect

study published in the journal Science in 2010 suggested that ketamine restores brain function through a process called synaptogenesis. Scientists at Yale University found that ketamine not only improved depression-like behavior in rats but also promoted the growth of new synaptic connections between neurons in the brain.

mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.

Psychedelic-Assisted Psychotherapy A Paradigm Shift in Psychiatric Research and Development

Psychedelics Promote Structural and Functional Neural Plasticity.

Even a low-dose infusion can cause intense hallucinations. Patients often describe a kind of lucid dreaming or dissociative state in which they lose track of time and feel separated from their bodies. Many enjoy it; some don’t. But studies at NIMH and elsewhere suggest that the psychedelic experience may play a small but significant role in the drug’s efficacy.

“It’s one of the things that’s really striking,” says Steven Levine, a Princeton, N.J., psychiatrist who estimates that he has treated 500 patients with ketamine since 2011. “With depression, people often feel very isolated and disconnected. Ketamine seems to leave something indelible behind. People use remarkably similar language to describe their experience: ‘a sense of connection to other people,’ ‘a greater sense of connection to the universe.’ ”

Although bladder problems and cognitive deficits have been reported among long-term ketamine abusers, none of these effects have been observed in low-dose clinical trials. In addition to depression, the drug is being studied for its effectiveness in treating obsessive-compulsive disorder, post-traumatic stress disorder, extreme anxiety and Rett syndrome, a rare developmental disorder on the autism spectrum.

Booster treatments

The drug’s fleeting remission effect has led many patients to seek booster infusions. Hartman, for one, began his search before he even left his hospital room in Bethesda.

Four years ago, he couldn’t find a doctor in the Pacific Northwest willing to administer ketamine. “At the time, psychiatrists hovered between willful ignorance and outright opposition to it,” says Hartman, whose depression began creeping back a few weeks after his return to Seattle.

It took nine months before he found an anesthesiologist in New York who was treating patients with ketamine. Soon, he was flying back and forth across the country for bimonthly infusions.

Upon his request, he received the same dosage and routine he’d received in Bethesda: six infusions over two weeks. And with each return to New York, his relief seemed to last a little longer. These days, he says that his periods of remission between infusions often stretch to six months. He says he no longer takes any medication for depression besides ketamine.

“I don’t consider myself permanently cured, but now it’s something I can manage,” Hartman says, “like diabetes or arthritis. Before, it was completely unmanageable. It dominated my life and prevented me from functioning.”

In 2012 he helped found the Ketamine Advocacy Network, a group that vets ketamine clinics, advocates for insurance coverage and spreads the word about the drug.

And word has indeed spread. Ketamine clinics, typically operated by psychiatrists or anesthesiologists, are popping up in major cities around the country.

Levine, for one, is about to expand from New Jersey to Denver and Baltimore. Portland’s Abreu recently opened a second clinic in Seattle.

Depression is big business. An estimated 15.7 million adults in the United States experienced at least one major depressive episode in 2014, according to the NIMH.

“There’s a great unmet need in depression,” says Gerard Sanacora, director of the Yale Depression Research Program. “We think this is an extremely important treatment. The concern comes if people start using ketamine before CBT [cognitive behavioral therapy] or Prozac. Maybe someday it will be a first-line treatment. But we’re not there yet.”

Many unknowns

Sanacora says a lot more research is required. “It’s a medication that can have big changes in heart rate and blood pressure. There are so many unknowns, I’m not sure it should be used more widely till we understand its long-term benefits and risks.”

While a single dose of ketamine is cheaper than a $2 bottle of water, the cost to the consumer varies wildly, running anywhere between $500 and $1,500 per treatment. The drug itself is easily available in any pharmacy, and doctors are free to prescribe it — as with any medication approved by the Food and Drug Administration — for off-label use. Practitioners attribute the expense to medical monitoring of patients and IV equipment required during an infusion.

There is no registry for tracking the number of patients being treated with ketamine for depression, the frequency of those treatments, dosage levels, follow-up care and adverse effects.

“We clearly need more standardization in its use,” Zarate says. “We still don’t know what the proper dose should be. We need to do more studies. It still, in my opinion, should be used predominantly in a research setting or highly specialized clinic.”

As a drug once known almost exclusively to anesthesiologists, ketamine now falls into a gray zone.

“Most anesthesiologists don’t do mental health, and there’s no way a psychiatrist feels comfortable putting an IV in someone’s arm,” Abreu says.

It’s a drug, in other words, that practically demands collaboration. Instead, it has set off a turf war. As the use of ketamine looks likely to grow, many psychiatrists say that use of ketamine for depression should be left to them.

“The bottom line is you’re treating depression,” says psychiatrist David Feifel, director of the Center for Advanced Treatment of Mood and Anxiety Disorders at the University of California at San Diego. “And this isn’t garden-variety depression. The people coming in for ketamine are people who have the toughest, potentially most dangerous depressions. I think it’s a disaster if anesthesiologists feel competent to monitor these patients. Many of them have bipolar disorder and are in danger of becoming manic. My question [to anesthesiologists] is: ‘Do you feel comfortable that you can pick up mania?’ ”

But ketamine has flourished from the ground up and with little or no advertising. The demand has come primarily from patients and their families; Zarate, for instance, says he receives “at least 100 emails a day” from patients.

Nearly every one of them wants to know where they can get it.


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Exploring the Relationship Between Depression and Dementia

Depression may be a marker for early dementia as the JAMA article above discusses. Antidepressants don’t work as well in the elderly either, possibly because depression is a different disorder than in younger individuals. Also, the article mentions that depression in youth is a risk for dementia as well.

Exploring the Relationship Between Depression and Dementia

Researchers are still trying to tease out the relationship between depression and dementia. While depression does not appear to cause dementia, it likely is a risk factor, just as dementia is a risk factor for depression, said George Alexopoulos, MD, founder and director of the Weill-Cornell Institute of Geriatric Psychiatry. At least 20% of people with dementia develop a depressive syndrome, Alexopoulos said.

Often, though, the depression comes first. Some studies suggest that depression in early life is a risk factor for dementia, while depression later in life can be a prodrome of dementia, Alexopoulos said. Although findings are mixed, a 2014 review of the literature concluded that there is convincing evidence to suggest that depression can be a risk factor and a prodromal symptom of dementia.

In a more recent large longitudinal cohort study published in 2017 in JAMA Psychiatry, researchers followed the trajectory of depressive symptoms and dementia in 10 189 UK men and women over 28 years. Unlike some previous studies, this one found that depressive symptoms in midlife, even if chronic or recurring, were not associated with an increased risk of dementia. However, participants with depressive symptoms later in life had a higher risk of dementia. Depressive symptoms appear to be a prodromal feature of dementia or, perhaps, share common causes, such as neurodegeneration and inflammation, but they do not appear to increase the risk of dementia, according to the authors.

In contrast, another longitudinal study involving 4992 older Australian men, published 2 months earlier, found that those who had a history of depression earlier in life did have a higher risk of dementia than those who did not. However, the association was greater in men who were depressed when they entered the study. Treatment with antidepressants did not decrease the risk of depression-associated dementia, leading the authors to conclude that late-life depression should be considered an early sign of dementia, not a modifiable risk factor.

“Any time you have the first episode (of depression) at a later age, that’s always concerning for a neurodegenerative disorder,” said Anna Burke, MD, a geriatric psychiatrist and the director of neuropsychiatry at Barrow Neurological Institute in Phoenix, who was not involved with either study.

Raj Shah, MD, an associate professor of family medicine with the Rush University Alzheimer Disease Center in Chicago, recommends that a first episode of depression in older individuals be considered a sentinel event, the same way a fall is. Both events should spur questions about whether patients need to have their medication adjusted or whether the fall or the mood change is a marker of other conditions, Shah said.

Difficult Diagnosis

Depression is often overlooked when it accompanies dementia, Burke said.

“The problem is the DSM-5 [Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition)] criteria we use for major depressive disorder don’t necessarily fit for this population, much like in children, where depression presents differently,” she said.

As with children, adults living with dementia and depression might not talk about emotional pain or feeling down, Burke said. Instead, they might exhibit irritability—“they may just get a little more feisty,” she said—and an increase in somatic symptoms, such as aches and pains and gastrointestinal complaints.

“Sometimes people don’t get diagnosed with depression because there is such a huge overlap in symptoms between depression and dementia as well as growing older,” Burke said. Symptoms common to both depression and dementia include loss of interest in activities and hobbies, social withdrawal, and impaired thinking.

Because the symptoms overlap, caregivers might not recognize depression in people with dementia. “I’m often the first person to bring it up,” Burke said. “Even when people do seek treatment in the community, many physicians are not focused on treating anything beyond the memory changes. Nobody ever really discusses the behavioral changes, the changes in mood.”

Still, Alexopoulos said, “If you see the patient at the wrong time, you may miss it. Patients with dementia underreport depression, and caregivers are unreliable reporters.”

As David Steffens, MD, MHS, explained, “It’s hard to notice a change in mood when somebody can’t really voice how they’re feeling.”

But that doesn’t mean depression is insignificant in the setting of dementia. “One reason to treat depression is that depression makes underlying cognitive impairment much worse,” said Steffens, chairman of psychiatry at the University of Connecticut. “You want to give them their best cognitive chance.” Besides antidepressants, he said, psychiatrists have sometimes used electroconvulsive therapy to treat severe depression in people with mild dementia.

Drug Therapy

The prescribing of antidepressants to people with dementia appears to be increasing, according to a UK studypublished in 2017. Trends in diagnosis and treatment of people with dementia suggest that the proportion prescribed antidepressants rose from 28% to 36.6% from 2005 to 2015.

Antidepressants don’t seem to work as well in people with dementia, possibly because “depression in dementia is a different illness” than depression in people with normal cognition, Alexopoulos said. Cognitive control dysfunction in dementia appears to decrease the effectiveness of some selective serotonin reuptake inhibitors (SSRIs), he and his coauthors wrote in a 2015 article. “I think it is appropriate to try to treat with as little medication as you can,” in part because polypharmacy can lead to delirium syndromes in patients with dementia, Alexopoulos said.

Although the study of Australian men found that taking antidepressants did not reduce the risk of depression-associated dementia, recent research suggests that the drugs might slow the progression to dementia in people with MCI and depression. That study, published in 2017, found that taking the antidepressant citalopram (Celexa), an SSRI, for more than 4 years was associated with a delay in progression from MCI to Alzheimer disease by about 3 years. “Three years is a big deal in this age group,” Alexopoulos said. Experiments in mice and healthy humans have shown that citalopram reduces amyloid plaque, one of the hallmarks of Alzheimer disease.

Treating depression in people with MCI with antidepressants might slow the progression to dementia, but little is known about whether drugs and other interventions developed to treat Alzheimer disease have any effect on depression.

Most clinical trials of potential Alzheimer disease treatments do not consider neuropsychiatric symptoms such as depression or irritability as primary research targets, even though “these symptoms are widely recognized as the most stressful and challenging manifestations of dementia,” concluded authors of a recent review article. Only 17.7% of the relevant studies they found on tested the effect of pharmacological or nonpharmacological interventions on neuropsychiatric symptoms, they wrote.

Beyond Medication and Talk Therapy

People with MCI might still be able to benefit from cognitive behavioral therapy or psychotherapy, but that becomes less likely as they decline, Burke said. “A huge part of psychotherapy is being able to remember what happened in a session.”

Even individuals whose dementia is too advanced for talk therapy can still benefit from lifestyle changes, though, Burke said. Engaging them in social activities and modifying their environment to minimize triggers that make them anxious or irritable can help improve their quality of life, she said.

A recent pilot study suggested that increasing exposure to daylight can reduce depression in people with dementia. The 12-week study involved 77 people living in 8 dementia care communities. At 4 of the communities, staff took study participants to a room with windows for socialization from 8 am to 10 am each day. At the other 4 communities, staff took study participants to socialize in the mornings in a room illuminated only with typical artificial light.

At the end of the study, participants who had socialized in the rooms with daylight had a statistically significant decrease in their scores on the Cornell Scale for Depression in Dementia, while the other participants did not. More studies are needed to determine the appropriate timing, duration, wavelength, and intensity of light exposure for adults with dementia, the researchers concluded.

Another recent study suggested a perceived lack of social engagement is also associated with depressive symptoms in people with dementia. Researchers measured social engagement, medication use, and depressive symptoms in 402 community-dwelling adults whose average age was 86 years. The data were collected during the first interview at which the participants met the criteria for a dementia diagnosis. The researchers found a link between perceived social isolation and the severity of depressive symptoms but not between antidepressant use and severity of depressive symptoms.

Because the study participants were newly diagnosed, their dementia was mild to moderate. “At that stage, people can still engage,” coauthor Shah said. “If we break down some of the stigma around the diagnosis of dementia, it will help people build cultures of support and inclusiveness.”

Cornell Depression Index

The Cornell Scale for Depression in Dementia

Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant


Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram.


We studied older subjects with major depression (N = 53) and non-depressed subjects (N = 30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color-Word Test, Tower of London (ToL), and Dementia Rating Scale – Initiation/Perseveration domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks.


There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control cluster (abnormal Stroop, ToL, DRS-IP), a Reward-Related cluster (IGT), and an Executively Unimpaired cluster. Decline in depression was greater in the Executively Unimpaired (t = −2.09, df = 331, p = 0.0375) and the Reward-Related (t = −2.33, df = 331, p = 0.0202) clusters than the Cognitive Control cluster. The Executively Unimpaired cluster (t = 2.17, df = 331, p = 0.03) and the Reward-Related cluster (t = 2.03, df = 331, p = 0.0433) had a higher probability of remission than the Cognitive Control cluster.


Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to selective serotonin reuptake inhibitors who may require structured psychotherapy.

An Antidepressant Decreases CSF Ab Production in
Healthy Individuals and in Transgenic AD Mice

Serotonin signaling suppresses generation of amyloid-b (Ab) in vitro and in animal models of Alzheimer’s disease
(AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant
citalopram, a selective serotonin reuptake inhibitor, decreased Ab in brain interstitial fluid in a dose-dependent
manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered
citalopram. Citalopram arrested the growth of preexisting plaques and reduced the appearance of
new plaques by 78%. In healthy human volunteers, citalopram’s effects on Ab production and Ab concentrations
in cerebrospinal fluid (CSF) were measured prospectively using stable isotope labeling kinetics, with CSF sampling
during acute dosing of citalopram. Ab production in CSF was slowed by 37% in the citalopram group compared to
placebo. This change was associated with a 38% decrease in total CSF Ab concentrations in the drug-treated group.
The ability to safely decrease Ab concentrations is potentially important as a preventive strategy for AD. This study
demonstrates key target engagement for future AD prevention trials.

An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice


Trajectories of Depressive Symptoms Before Diagnosis of Dementia

Trajectories of Depressive Symptoms Before Diagnosis of Dementia

Key Points

Question  Does the course of depressive symptoms over adulthood in those who develop dementia differ from those who remain dementia free?

Findings  This cohort study found that depressive symptoms in late life but not midlife were associated with increased risk for dementia; analysis of depressive symptoms spanning 28 years showed them to emerge approximately a decade prior to dementia diagnosis. No substantive differences in depressive symptoms were apparent between those who went on to develop dementia and dementia-free persons 12 to 28 years prior to dementia diagnosis.

Meaning  The association between depressive symptoms and dementia in older adults may be primarily due to common causes or depressive symptoms being a feature of the preclinical phase of dementia.


Brain Marker Predicts Depression Outcomes

Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression

Individuals with major depression and higher rostral anterior cingulate cortex (rACC) theta activity prior to treatment had better outcomes than those with less rACC theta activity at baseline, according to a study in JAMA Psychiatry.

The 296 patients with major depressive disorder were randomized to receive sertraline hydrochloride or placebo for 8 weeks. Among 248 patients with usable electroencephalographic (EEG) recordings, higher rACC theta activity at baseline and week 1 predicted greater depressive-symptom improvement in both placebo and treatment groups, even after controlling for other clinical and demographic variables associated with treatment outcome.

According to the authors, rACC theta activity has incremental predictive validity as a marker of treatment outcome.


Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

New Genetic Links to Depression May Pave the Way for Novel Treatment Strategies

JAMA. 2018;320(1):20-21. doi:10.1001/jama.2017.12862

Despite a revolution in depression awareness and treatment in the 1990s and the approval of more than 20 drugs for the condition, many individuals still struggle with the condition. However, the recent discovery of new regions in the human genome associated with susceptibility to major depressive disorder (MDD) could pave the way for novel therapeutic strategies and improved diagnostics.

One of the largest genome-wide association studies to date has identified new genetic risk factors for MDD.

One of the largest genome-wide association studies to date has identified new genetic risk factors for MDD.

Reported in Nature Genetics, the findings are based on a genome-wide association meta-analysis involving 135 458 clinically assessed and self-reported cases of MDD, as well as 344 901 controls. One of the largest ever conducted in psychiatric genetics, the study revealed 44 regions of the genome that may influence depression, 30 of which are novel and 14 of which had been previously identified. Some of these genetic variants are directly linked to the targets of current antidepressant medications.

“We were gratified to see overlap with pharmacologically defined targets of antidepressants. This suggests that our results are informative for treatment and that greater precision could lead to novel therapeutics,” said co–senior author Patrick Sullivan, MD, director of the Center for Psychiatric Genomics at the University of North Carolina School of Medicine at Chapel Hill.

Analyses by Sullivan, in collaboration with more than 200 investigators around the globe in diverse fields of biomedical research, uncovered different gene expression patterns between cases and controls in the prefrontal and anterior cingulate cortex—regions of the brain involved in cognition and emotion. Furthermore, the genetic findings implicated neurons rather than microglia and astrocytes as being the most important cell types involved in MDD.

The genetic associations tended to occur in genomic regions conserved across a range of placental mammals. Importantly, exons did not show enrichment, suggesting that genetic variants that change sequences within coding regions may not play a large role in MDD. Instead, results pointed to the potential importance of alternative RNA splicing, indicating that risk may be mediated not by changes in isolated amino acids but rather by changes in the proportions of protein isoforms generated from a gene.

The scientists also looked for potential genetic correlations between MDD and various other disorders and human traits. Although there was no evidence of genetic correlation with IQ, both lower educational attainment and higher body mass index (BMI) were correlated with MDD. Bidirectional mendelian randomization further suggested lower educational attainment and higher BMI may be causal risk factors for MDD.

Identifying potentially causal loci has proved challenging in the past due to the likely influence of many genetic loci, each with small effects, and MDD’s moderate heritability, high prevalence, and heterogeneity of genetic and nongenetic factors.

“We overcame these difficulties via a very large-scale collaboration. This paper was a labor of love by a dedicated consortium who have been at it for a decade,” said Sullivan.

Deeper examinations of the genetic architecture of MDD uncovered a link with daytime sleepiness, insomnia, and tiredness, as well as a partly shared biology between depression and schizophrenia. Significant positive correlations were also seen between MDD and numerous adult- and childhood-onset psychiatric disorders, suggesting that MDD is not a discrete pathophysiological entity.

Ultimately, detailed genetic analyses may help clinicians stratify patients according to their risk of recurrent depression, poor outcomes, poor treatment response, and developing other psychiatric disorders. This could form a cornerstone of precision medicine in psychiatry, according to the authors.

“This pioneering study is incredibly important for 2 reasons,” said Josh Gordon, MD, PhD, who is director of the US National Institute of Mental Health and was not involved with the study. “First, it reaffirms the value of large-scale collaborations, particularly in identifying the complex genetics underlying psychiatric illness. Second, it confirms the genetic roots for depression, offering important biological clues that we hope will lead to new and better treatments.”

Those clues include the identification of potentially novel networks involved in the neurobiology of depression, such as developmental gene regulatory networks (RBFOX1RBFOX2RBFOX3, and CELF4); genes whose mRNAs are bound by fragile X mental retardation protein; genes with roles in neuronal morphogenesis, projection, or differentiation; genes associated with schizophrenia; genes involved in cytokine and immune response; and genes known to bind to the retinoid X receptor, among others.

Additional genetic analyses of individuals with and without MDD are needed to test the validity of the associations uncovered in this study and to reveal others. “Our paper expanded our knowledge base by 3-fold, but there are more [genetic associations] out there to be discovered,” said Sullivan. “We need more data, and we need careful studies of where and when these findings may have a clinical impact. These [studies] are in progress.”

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Prior ingestion of exogenous ketone monoester attenuates glycemic response to oral glucose

Drinking a ketone supplement drink has been shown for the first time to help lower blood sugar levels which may represent a potential method to control spikes in blood sugar experienced by diabetics as published in the Journal of Physiology.

Obesity and type 2 diabetes have grown to reach epidemic levels globally, such conditions are associated with high blood sugar that can damage vessels that supply blood to vital organs and increase risks for stroke and heart disease.

Infusing ketones into the bloodstream has been shown to reduce blood sugar levels. This study shows that a single drink of ketone ester supplement enabled better control of blood sugar by reducing spikes in sugar levels which was demonstrated by researchers from the University of British Columbia and the University of Oxford.

20 healthy subjects on 2 occasions consumed either a placebo or ketone monoester supplement after a 10 hour fasting period, 30 minutes after subjects consumed a drink containing 75 grams of sugar, over the entire 2.5 hour protocol for glucose, hormone, and lipid analyses blood samples were collected every 15-30 minutes.

As this study was conducted on healthy young individuals additional studies are required to reduce the confounding influence of insulin resistance, medications, and beta-cell dysfunction to determine whether it will apply to individuals with obesity, prediabetes, and type 2 diabetes, and to gain better understandings of the physiological mechanisms underpinning improved blood sugar control. Control drinks had to be made to mimic that of the ketone supplements to blind the subjects, the ketone supplements were noted to not taste good.

Should the same responses be seen in other subjects with or at risk for type 2 diabetes it may be possible that ketone monoester supplements could be used in interventions to help lower glucose levels and improve metabolic health; additional studies are currently underway to investigate.

 The Physiological Society.

Journal Reference:

Etienne Myette-Côté, Helena Neudorf, Hossein Rafiei, Kieran Clarke, Jonathan Peter Little. Prior ingestion of exogenous ketone monoester attenuates the glycemic response to an oral glucose tolerance test in healthy young individualsThe Journal of Physiology, 2018; DOI: 10.1113/JP275709


Shivering in the cold? Exercise may protect against muscle fatigue

16 August 2018. New research published in The Journal of Physiology highlights how exercise could help people exposed to extreme temperatures protect themselves from the cold. This could be useful for people who live and work in very cold conditions.

Shivering is one of the first defences against cold and it boosts the body’s heat production. Shivering can only warm you up for so long and after a few hours your muscles will run out of fuel and will grow too tired to contract. Exercise helps build-up muscle in the limbs and this new research shows that this exercise could help the muscle shiver longer and keep people warmer for longer. Therefore this suggests that people preparing to live in extreme cold conditions should exercise in order to protect against fatigue to their muscles caused by shivering.

The study, conducted by the University of Guelph and the University of Copenhagen, assessed mice that had trained with voluntary wheels and had been exposed to cold temperature conditions. During cold exposure their changes in body weight, food intake, blood sugar levels and rectal temperature were measured, in addition to an examination of their limb muscle and fat tissue. Mice that did not exercise lost a significant amount of weight when exposed to the cold however exercise-trained mice were better able to maintain their core temperature.

It is important to note that the researchers were unable to directly measure limb muscle activity during cold exposure, which will be essential for future exploration.

David C. Wright, corresponding author on the study, commented on the future direction of the work ‘In this study we show that exercise training helps build limb muscle and in turn offers better protection against cold conditions. We would now like to determine if the responses that we saw in males also occurred in females. It would also be interesting to determine if obesity impacts the effects that we saw.’


Notes for Editors

1. Prior exercise training improves cold tolerance independent of indices associated with non-shivering thermogenesis:

Prior exercise training improves cold tolerance independent of indices associated with non‐shivering thermogenesis  << Paper

Key points:

Mammals defend against cold-induced reductions in body temperature through both shivering

and non-shivering thermogenesis. The activation of non-shivering thermogenesis is primarily

driven by uncoupling protein-1 in brown adipose tissue and to a lesser degree by the browning

of white adipose tissue.

Endurance exercise has also been shown to increase markers of white adipose tissue browning.

This study aimed to determine whether prior exercise training would alter the response to

a cold challenge and if this would be associated with differences in indices of non-shivering


It is shown that exercise training protects against cold-induced weight loss by increasing food

intake. Exercise-trained mice were better able to maintain their core temperature, independent

of differences in markers of non-shivering thermogenesis.

2. The Journal of Physiology publishes advances in physiology which increase our understanding of how our bodies function in health and disease. 

Low Dose Naltrexone | LDN | 703-844-0184 | Fairfax, Va | IV drip and hydration therapies | LOW dose Naltrexone for chronic diseases

Low Dose Naltrexone has been utilized for numerous treatments. Look at the data below for Chrone’s disease, fibromyalgia, and M.S and chronic pain. Naltrexone seems to be very helpful.

Low dose Naltrexone for induction of remission in inflammatory bowel disease patients.

Low dose Naltrexone for induction of remission in IBD



Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function.


Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples.


Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected.


Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.

The use of LDN in clinical settings is gaining interest, with Crohn’s disease, multiple sclerosis
and fibromyalgia described as potential targets for treatment with LDN.


Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.

Fibromyalgia symptoms are reduced by low-dose naltrexone a pilot study.

Fibromyalgia is a common clinical entity that can be devastating to patients and frustrating for pain management specialists. Up to 5% of women and up to 2% of men may be diagnosed with fibromyalgia. Fibromyalgia can lead to lost productivity and medical costs due to pharmacologic agents utilized for treatment. Patients may describe pain, fatigue, gastrointestinal, and other symptoms. Fibromyalgia has been described as a member of the “central sensitivity syndromes”, which are disorders including chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Centrally active cytokines that are proinflammatory are believed to lead to fatigue, increased pain sensitivity, and similar symptoms of fibromyalgia. Currently, the FDA has approved pregabalin, duloxetine and milnacipran for use in the treatment of patients with fibromyalgia. Naltrexone is an agent that the authors of this study suggest may be an adjunct in the treatment of patients with fibromyalgia. Compared to the other drugs, naltrexone is relatively inexpensive, costing less than $40 per month (per the article). LDN is suggested for study in this population because of its ability to antagonize opioids receptors, and decrease the superoxides and inflammatory mediators in microglia cells in the central nervous system (CNS). Theoretically, LDN is believed to block beta-endorphins from binding to receptors for a short time, leading to an increased production of beta-endorphins, and, therefore, clinical effect. LDN has also been evaluated in patients with multiple sclerosis and Crohn’s disease.

Patients included in the study were required to meet the American College of Rheumatology criteria for fibromyalgia (1990), and excluded were those with prior use of opioids, a history of autoimmune disease, those positive for rheumatoid factor, or those with an elevated (over 60mm/h) erythrocyte sedimentation rate (ESR). Each participant in the study received a baseline evaluation (2 weeks), a placebo (2 weeks), LDN 4.5mg (8 weeks), and washout (2 weeks). This design allowed patients to have a control phase allowing investigators to account for patient variability. Patients self-reported their symptoms via a Palm handheld computer. Questions included the severity of the patient’s pain on a visual analogue scale (VAS) from 0-100, fatigue, sadness, highest pain level, stress, sleep quality, the ability to think, concentration, gastrointestinal (GI) symptoms, and headache. Study patients also had mechanical, thermal- and cold-sensitivity testing in a lab every 2 weeks to note the effect of naltrexone on sensitivity. Side effects were minimal with drug administration, with vivid dreams and nausea and insomnia being reported. Naltrexone administration was shown to increase thermal pain thresholds by 0.9 degrees Celsius, and improve mechanical thresholds. The drug administration did not have an impact on cold pain thresholds, however. The investigators found that naltrexone had a statistically significant impact on daily pain, highest pain felt, fatigue, and stress, decreasing these in patients treated. The following parameters did not achieve statistical significance: sleep quality, GI problems, headaches, thinking and concentration, and sadness. The investigators propose that fibromyalgia is a disease entity that describes clinical conditions presenting similarly by noting that baseline levels of the ESR test correlated positively with response to naltrexone. They hypothesize that the presence of elevated ESR may identify patients who may be more responsive to LDN than those who are not. Younger and Mackey advise testing for liver functioning as well as observing for the theoretical risk of infection that may be present with administration of naltrexone. The study would be made stronger with a larger patient population and a double-blinded construction. Despite this limitation, the study does seem to suggest the need for future evaluation of the use of LDN in the treatment of patients with pain of fibromyalgia.

  1. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis.

    Gironi M, Martinelli-Boneschi F, Sacerdote P, Solaro C, Zaffaroni M, Cavarretta R, Moiola L, Bucello S, Radaelli M, Pilato V, Rodegher M, Cursi M, Franchi S, Martinelli V, Nemni R, Comi G, Martino G

    Mult Scler 2008 Sep; 8(14):1076-83

    PMID: 18728058

  2. Low-dose naltrexone therapy improves active Crohn’s disease.

    Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS

    Am J Gastroenterol 2007 Apr; 4(102):820-8

    PMID: 17222320 <LDN Resource


    Low dose naltrexone for treatment of multiple sclerosis

    Low Dose Naltrexone for Treatment of Multiple Sclerosis A Retrospective Chart Review of Safety and Tolerability

    A potential alternative or adjunctive

    therapy for MS is related to knowledge
    about the endogenous opioid system and
    its ability to modulate autoimmune diseases
    using animal models of MS.7–10 This
    novel biological pathway involves an endogenous
    opioid growth factor, chemically
    termed methionine enkephalin, and its
    nuclear-associated receptor, Opioid growth
    factor receptor.11 Modulation of this pathway
    by exogenous administration of opioid
    antagonists such as naltrexone (NTX) has
    been shown to mediate cell replication including
    T lymphocytes, astrocytes, and
    other glia that are associated with MS
    inflammation and degeneration.9 The magnitude
    and direction of change in cell
    proliferation is dependent on the duration
    of opioid receptor blockade.12 Low dosages
    of NTX (LDN), given once daily block the receptor intermittently and result
    in inhibited cell replication.

  3. Three clinical trials of LDN in MS
    have been conducted and report that
    LDN increases the quality of life of MS
    patients.13–15 Cree et al14 concluded from
    a trial of 8 weeks that 4.5 mg LDN daily
    was a safe therapy that improved quality
    of life, whereas Sharafaddinzadeh et al13
    reported safety after 17 weeks of treatment
    and recommended that longer trials be
    conducted to evaluate efficacy. Gironi et al15
    studied primary progressive MS patients
    treated with LDN for 6 months and reported
    increased endogenous opioid levels
    in the patients and improved MS. The LDN
    treatment of patients with other autoimmune
    diseases including Crohn’s disease
    and fibromyalgia has demonstrated safety
    and efficacy of the therapy.16,17 A major
    symptom of MS is fatigue,18 which is one
    of the many characteristics that patients seek
    to alleviate. Improvement in fatigue was cited
    in these clinical studies after LDN therapy,
    which suggests that there is a potential link
    between upregulated endogenous opioid
    systems and fatigue. Gironi et al15 reported
    elevated β-endorphin levels at 1, 3, and
    6 months after the onset of treatment, with
    β-endorphin levels remaining elevated for
    an additional month after LDN was discontinued.

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain

Use of LDN in chronic pain
LDN has been tested experimentally in a small number of
chronic pain conditions. One such condition is fibromyalgia
(FM). FM is a chronic pain disorder that is characterized by
diffuse musculoskeletal pain and sensitivity to mechanical
stimulation as well as profound fatigue, cognitive disruption,
and sleep difficulty. Although FM does not respond to common
anti-inflammatories and does not seem to be an inflammatory
disorder in the classic sense [13], inflammatory processes
may still be involved [14]. We have shown in two
separate, small clinical trials that LDN may be an effective
treatment for FM. In both trials, LDN was administered at
4.5 mg daily, once at night before bedtime. In the first crossover
trial, published in 2009 [15], LDN reduced fibromyalgia
pain significantly greater than placebo in 6 out of the 10
women. While the pilot study was encouraging, it had limitations
such as a single-blind design. To help validate the
findings, a second study in 30 women with fibromyalgia
was conducted [9]. In that double-blind, crossover,
counterbalanced study, 57 % of the participants were observed
to exhibit a significant (1/3) reduction of pain during LDN. At
the end of the LDN treatment, half of the participants reported
feeling “much improved” or “very much improved” from
LDN (Fig. 1). Together, these two studies suggest that LDN
is superior to placebo in reducing the pain associated with

Evidence for a novel central anti-inflammatory action
of naltrexone

Anti-inflammatory effects of LDN in vivo and in vitro
In describing LDN’s clinical utility, it is important to understand
the dual physiologic mechanisms of naltrexone and
other opioid antagonists. Most clinicians are familiar with
naltrexone as a potent and nonselective opioid receptor antagonist
and treatment for opioid addiction. Naltrexone, at typical
dosages, significantly blocks activity at mu- and delta-opioid
receptors as well as (to a lesser extent) kappa-opioid receptors
[16]. Because beta-endorphin activity at mu-opioid receptors
is associated with endogenous analgesic processes, it may
seem counterintuitive to administer naltrexone to individuals
with chronic pain, as we might expect the medication to
reduce analgesia produced by beneficial endogenous opioid
Naltrexone, however, exerts its effects on humans via at
least two distinct receptor mechanisms. In addition to the
antagonist effect on mu-opioid and other opioid receptors,
naltrexone simultaneously has an antagonist effect on nonopioid
receptors (Toll-like receptor 4 or TLR4) that are found
on macrophages such as microglia [17]. It is via the nonopioid
antagonist path that LDN is thought to exert its antiinflammatory
effects. Microglia are central nervous system
immune cells that are activated by a wide range of triggers
[18]. Once activated, microglia produce inflammatory and
excitatory factors that can cause sickness behaviors such as
pain sensitivity, fatigue, cognitive disruption, sleep disorders,
mood disorders, and general malaise [19]. When chronically
activated, the resulting proinflammatory cascade may become
neurotoxic, causing several deleterious effects [20]. Given the
wide variety of inflammatory factors produced by activated
microglia (e.g., proinflammatory cytokines, substance P, nitric
oxide, and excitatory amino acids) [21], a range of symptoms
and medical outcomes could share the pathophysiological
mechanism of central inflammation. Conditions such as fibromyalgia
may involve chronic glial cell activation and subsequent
production of proinflammatory factors. The hypothesis
is indirectly and partially supported by the high degree of
symptomatic overlap between fibromyalgia and cytokineinduced
sickness behaviors.
Both naloxone and naltrexone have been demonstrated to
exert neuroprotective and analgesic effects [22]. The neuroprotective
action appears to result when microglia activation in the brain and spinal cord is inhibited [23]. By suppressing
microglia activation, naloxone reduces the production of reactive
oxygen species and other potentially neuroexcitatory
and neurotoxic chemicals [24]. The anti-inflammatory effect
of opioid antagonists may also extend to the periphery, as
evidenced by suppressed TNF-alpha, IL-6, MCP-1, and other
inflammatory agents in peripheral macrophages [25]. It should
be noted that most animal work has used naloxone, while
most human work has used naltrexone (because of its higher
oral availability). We cannot discount the possibility that
findings from one compound would imperfectly translate to
the other.