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Dean Pomerleau posted a topic in CR PracticeAll, One of the initial motivations for studying the possible benefits of the Omega-3s PUFAs DHA & EPA came from observations that the Inuits of Greenland, whose diet contains a very high proportion of polyunsaturated fat from cold-water fish and marine mammals, suffer from relatively low rates of cardiovascular disease. But randomized control trials of the benefits of DHA / EPA supplements for (primary or secondary) prevention of cardiovascular disease have generally been disappointing (e.g. ). This new study  in Science, might suggest at least part of the explanation for this apparent paradox. That paper used population-genetic analysis of Greenland Inuits to discover regions of two chromosomes that seem to have experienced strong selection in the recent past. Those regions also happen to contain genes involved in fatty acid metabolism; and the variants of the genes that have increased in frequency in Inuits are also associated with small stature and lower weight. From the abstract: By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs. In an accompanying commentary, there is a fascinating map of relatively recent human genetic variations and where they occur around the world (click to enlarge): The one that isn't shown that I find very interesting is the salivary amylase gene (AMY1) for digesting starch. Several studies (e.g. ) have found that the number of duplicates of the AMY1 a person has can vary from 2 to about 15 from one individual to the next. The more AMY1 copies you have, the better you are at digesting starch / carbohydrates, and the less prone you are to obesity . Study  looked at how the number of AMY1 copies varied between people of different ethnic groups and found a striking correlation between the amount of starch in their ancestral diet and the number of AMY1 copies their genome contained. Here is that result illustrated on a map (click to enlarge): In short, it appears that in cultures whose ancestral diet contained a large fraction of carbohydrates, more copies of the AMY1 gene were selected for since it helped them better process carbs. The bottom line appears to be that there is no "one size fits all" diet that is right for everyone. To some extent at least, the best diet for an individual depends on his/her genes. --Dean --------------------------------  Arch Intern Med. 2012 May 14;172(9):686-94. doi: 10.1001/archinternmed.2012.262. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Kwak SM(1), Myung SK, Lee YJ, Seo HG; Korean Meta-analysis Study Group. Collaborators: Myung SK, Ju W, Oh SW, Bae JH, Kim YK, Park CH, Jeon YJ, Lee EH, Chang YJ, Park SM, Eom CS, Lee YJ, Jung HS, Kwak SM. BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease. PMID: 22493407 -----------------  Science. 2015 Sep 18;349(6254):1343-1347. Greenlandic Inuit show genetic signatures of diet and climate adaptation. Fumagalli M(1), Moltke I(2), Grarup N(3), Racimo F(4), Bjerregaard P(5), Jørgensen ME(6), Korneliussen TS(7), Gerbault P(8), Skotte L(2), Linneberg A(9), Christensen C(10), Brandslund I(11), Jørgensen T(12), Huerta-Sánchez E(13), Schmidt EB(14), Pedersen O(3), Hansen T(15), Albrechtsen A(16), Nielsen R(17). The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs. Copyright © 2015, American Association for the Advancement of Science. PMID: 26383953 -----------------  Nat Genet. 2014 May;46(5):492-7. doi: 10.1038/ng.2939. Epub 2014 Mar 30. Low copy number of the salivary amylase gene predisposes to obesity. Falchi M(1), El-Sayed Moustafa JS(2), Takousis P(3), Pesce F(4), Bonnefond A(5), Andersson-Assarsson JC(6), Sudmant PH(7), Dorajoo R(8), Al-Shafai MN(9), Bottolo L(10), Ozdemir E(3), So HC(11), Davies RW(12), Patrice A(13), Dent R(14), Mangino M(15), Hysi PG(15), Dechaume A(16), Huyvaert M(16), Skinner J(17), Pigeyre M(18), Caiazzo R(18), Raverdy V(13), Vaillant E(16), Field S(19), Balkau B(20), Marre M(21), Visvikis-Siest S(22), Weill J(23), Poulain-Godefroy O(16), Jacobson P(24), Sjostrom L(24), Hammond CJ(15), Deloukas P(25), Sham PC(11), McPherson R(26), Lee J(27), Tai ES(28), Sladek R(29), Carlsson LM(24), Walley A(30), Eichler EE(31), Pattou F(18), Spector TD(32), Froguel P(33). Comment in Nat Rev Endocrinol. 2014 Jun;10(6):312. Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies. PMID: 24686848 -------------------------  Perry, G. H., Dominy, N. J., Claw, K. G., Lee, A. S., Fiegler, H., Redon, R., et al. (2007). Diet and the evolution of human amylase gene copy number variation. [10.1038/ng2123]. Nat Genet, 39(10), 1256-1260.
[Note: This is a thread spun off from a post on the Cool Tools" thread about my favorite treatment for dry, cracking skin, discussed below - Dean] Moisturizer: O'Keeffe's Working Hands Cream I know I'm not the only CR Practitioners to suffer on occasion from dry, cracked skin, particularly on the fingers. It seems to happen in the drier months of fall and winter. About a year ago I found a solution that works better than any I've ever tried, and that is O'Keeffe's Working Hands Cream (or in larger size for less per oz). This stuff is amazing, and the 3500+ 5-star reviews on Amazon show that other people feel the same way. Painful hand cracks that I thought I'd be stuck with for a week or more quickly went away after applying this stuff. Fortunately I haven't suffered from finger cracks lately, possibly because of regular application of this cream, or possibly because of sufficient healthy fats in my diet. But here is a before/after picture of the kind of cracking I'm talking about (ouch!) that this product can take care of (this is an example after 1-week of use by someone who purchased the cream). Here is a description of the product: O'Keeffe's Working Hands is an odorless unique skin therapy lotion to improve the health of your skin. A water based product that contains no oil -- No Greasy Feel -- the lotion for dry skin, skin repair, cracked skin, skin relief, skin care, and skin moisturizing. Absolutely odorless No greasy feel Hypo-allergenic Not tested on animals 100% recyclable packaging Created by a pharmacist 2.7 oz. Jar The first effective treatment specifically for people who suffer from cracked and split skin. The highly concentrated proprietary formulation stimulates the skin's natural repair process by hydrating the skin, altering pH balance and retaining moisture. Safe and effective on all skin types. But I have to admit, I haven't researched the ingredients, which are: Water, Glycerin, Stearic Acid, Ammonium Stearate, Ammonium Borate, Dimethicone, Paraffin, Hydropropylmethylcellulose, Allantoin, Diazolidinyl Urea, Octyldodecyl Stearate, Iodopropynyl Butylcarbamate If anyone sees anything they consider toxic (for topical application), please let me know. Otherwise, this hand cream really does the trick and I highly recommend it. --Dean
Dean Pomerleau posted a topic in CR PracticeAll, The idea that rapid weight loss can result in release of toxins stored (relatively harmlessly) in body fat cells gets bandied about pretty regularly. In fact I've done it myself several times in just the last couple days (here and here). I've never actually looked for evidence to support this conventional wisdom, which has left me with a nagging feeling of dis-ease. I try not to make claims that I can't back up with evidence. So I figured I would look into it and start a new thread to collect the evidence and encourage discussion about it. Coincidently (or perhaps not?!), Al Pater posted this new study  today, which bears directly on the topic. In it, researchers followed 32 women who had just given birth and were breast feeding to see how the level of persistent organic pollutants (POPs) in their breast milk changed as a function of postpartum weight loss. All the women lost at least some weight in the 24 weeks of the study, and sure enough, the amount of POPs in their breast milk was highly correlated with the amount of weight they lost: Among these women, the concentration of PCB 153 in HM was significantly (p = 0.04) higher at follow-up than at baseline. Weight loss was significantly positively associated with changes in concentrations of all studied POPs (2.0-2.4% increase per percent weight loss). Since these women probably weighed in the neighborhood of 140-180 lbs to start with, it appears that the level of toxins in their breast milk went up by about 1-2% per pound of weight loss. Since not all of the toxins released end up in breast milk (especially in men and non-lactating women!) I would expect the increase in toxin load circulating in the blood per pound of weight loss to be higher than that. So  definitely supports the idea that rapid weight loss increases circulating toxin load. But even more direct and conclusive evidence of dieting-induced toxin release is study . In , researchers followed 45 morbidly obese women for 6 months following either bariatric surgery or intensive dieting. These women were really heavy to start with - average BMI around 40. And they lost quite a bit of weight (-32lbs of body weight on average) in a relatively short period of time (six months). But in fact that translates into 1.23lbs per week of weight loss, which is very close to the maximum rate of weight loss we recommend around here, ~1lb per week. So what did they find? A very large increase in the same Persistent Organic Pollutants (POPs), to the tune of a 50% increase on average: In patients who lost weight, serum [total POP] levels displayed an increase after 6 months of approximately 50%. ... [T]he increase in [Total POP] serum levels after 6 months of weight loss was more pronounced in patients losing relatively more visceral adipose tissue. So even the kind of "slow-and-steady" weight loss we recommend of 1lb of weight per week results in a dramatic increase in toxin load that persists for at least six months. And visceral fat loss is a bigger factor contributing to toxin release than subcutaneous (love-handle) fat loss. In satisfying agreement with the 1-2% increase in POPs per pound of weight loss observed in , this study found that an average of 32lbs of weight loss resulted in a 50% increase in average serum POP level, which equates to ~1.5% increase in circulating POPs per pound of weight loss. So in general even 1lb of weight loss per week may be too rapid... Ah. That feels better. My cognitive dissonance is subsiding... Now I can go back to those two posts and insert a link to this thread. And now we have a place to point next time anyone makes the statement that rapid weight loss releases toxins into the blood. --Dean ------------  Chemosphere. 2016 Jun 6;159:96-102. doi: 10.1016/j.chemosphere.2016.05.077. Environmental organic pollutants in human milk before and after weight loss. Lignell S, Winkvist A, Bertz F, Rasmussen KM, Glynn A, Aune M, Brekke HK. Abstract Many persistent organic pollutants (POPs) are banned because they accumulate in organisms and are toxic. Lipophilic POPs are stored in maternal adipose tissue and concentrations in human milk (HM) may increase during weight loss. Our aim was to examine associations between weight loss and concentrations of chlorinated POPs in HM in lactating women participating in a weight loss study. We analysed POPs (PCB 28, PCB 153, HCB, DDE) in HM at 12 and 24 weeks postpartum from 32 women who participated in a randomized, 2 ? 2 factorial trial of diet and exercise for postpartum weight loss. Participants donated milk before and after the intervention period. We examined associations between weight loss and change in POP concentrations and estimated the intake of POPs by their breastfed infants. Most (n = 27) women lost weight during intervention, 0.45?0.30 kg/week (mean?SD). Among these women, the concentration of PCB 153 in HM was significantly (p = 0.04) higher at follow-up than at baseline. Weight loss was significantly positively associated with changes in concentrations of all studied POPs (2.0-2.4% increase per percent weight loss). Estimated mean intakes of POPs (ng/day) remained stable because infant milk consumption decreased during the study period. As infants gained weight, estimated mean intakes per kg body weight decreased 17-22%. Changes in concentrations of POPs in HM correlated positively with maternal weight loss, but it is unlikely that the balance between the benefits and risks of breastfeeding will change if the weight loss is restricted to 0.5 kg per week. KEYWORDS: Human milk; Obese; Overweight; POPs; Postpartum; Weight loss PMID: 27281542 ------------  J Clin Endocrinol Metab. 2015 Dec;100(12):4463-71. doi: 10.1210/jc.2015-2571. Epub 2015 Oct 15. Pivotal Role for the Visceral Fat Compartment in the Release of Persistent Organic Pollutants During Weight Loss. Dirinck E(1), Dirtu AC(1), Jorens PG(1), Malarvannan G(1), Covaci A(1), Van Gaal LF(1). Author information: (1)Department of Endocrinology, Diabetology, and Metabolism (E.D., L.F.V.G.), Toxicology Centre (A.C.D., G.M., A.C.), and Department of Intensive Care Medicine/Clinical Pharmacology (P.G.J.), Antwerp University Hospital, University of Antwerp, 2650 Edegem, Belgium. Full text: http://sci-hub.cc/10.1210/jc.2015-2571 CONTEXT: Polychlorinated biphenyls (PCBs), are implicated as potential endocrine disruptors and obesogens. These lipophilic substances are preferentially stored in the fat compartment and released into the circulation during weight loss. OBJECTIVE: The aim of this study was to examine the contribution of abdominal adiposity, and visceral adiposity in particular, to the increase of serum PCB levels during weight loss. MATERIALS AND METHODS: Fourty-five obese women were prospectively recruited. Twenty individuals received dietary counseling and 25 underwent bariatric surgery. Anthropometric data were collected and intra-abdominal adiposity was assessed by measurement computed tomography scanning of the abdominal fat compartment, delineating the visceral and subcutaneous compartment. Serum levels of 27 PCBs were determined and the sum of all PCBs (ΣPCBs) calculated. Follow-up measurements of anthropometric data, computed tomography scanning, and PCB levels were performed after 6 months in all patients. RESULTS: In patients who lost weight, serum ΣPCB levels displayed an increase after 6 months of approximately 50%. Both correlation and regression analysis, focusing on the relative contribution of the visceral vs the subcutaneous fat compartment, suggested that the increase in ΣPCB serum levels after 6 months of weight loss was more pronounced in patients losing relatively more visceral adipose tissue. This trend could be established in the diet-treated, but not the surgery-treated subgroup. CONCLUSION: Our study suggests that the contribution of PCBs released from the visceral fat compartment might be more pronounced compared with the subcutaneous fat compartment during weight loss. These findings are present in the entire study group whereas subanalysis of the diet vs surgery groups suggested the same effect in the diet group but failed to reach statistical significance in the surgery group. This suggests a possible weight-loss method-specific effect. PMID: 26469381