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Found 21 results

  1. Todd Allen

    What's Wrong with Eggs Now?!

    [Admin Note: Over on the LDL particle size thread, Todd asked the question of why eggs are bad. Seems like a question that deserves its own thread, given the recent supposed exoneration of dietary cholesterol. So here it is.] The important difference between consumption of dietary cholesterol, which has a negligible influence on heart disease risk, and cholesterol produced endogenously in the body (which can be a marker of risk, depending on a complete profile).... So why exactly is it that eggs are so damn bad? http://www.whfoods.com/genpage.php?tname=foodspice&dbid=92
  2. [Admin note: I've (obviously) shifted this conversation about HbA1c from its old home in the thread about best biomarkers to a new thread dedicated to the topic, since I think it is of general and lasting enough interest to deserve it's own thread.] Has Lustgarten mentioned his fasting glucose / post-prandial glucose / A1C% targets? I've been curious what others are setting for a goal in these areas. Last I checked, my A1C measured 4.9% on a low-carb diet (down from 5.3% on a higher carb diet), although I'm not sure if lower is continually better or if there's some optimal U-Curve there (beneficial hormesis?)
  3. Dean Pomerleau

    Omega-6 PUFA the Healthiest Fat?

    All, This new study [1] published today in JAMA (popular press account) seems to suggest Omega-6 PUFA is the type of fat associated with the lowest all-cause mortality. If followed the 80K women and 40K men in the Nurses/Health Professionals Studies checking their dietary intake of fats through food frequency questionnaires every couple years. During the followup period of 1980-2012, 33K of them died. Interestingly, being in the quintile that ate the most fat and the least carbs was associated with a 16% reduction in total mortality compared with the other extreme. Just goes to show how crappy the carbs are that the average American eats... Regarding the association of specific fats and mortality, here was the ordering of most-healthy to least-healthy: Omega-6 PUFA > MUFA > Omega-3 PUFA > Saturated Fat > Trans-fat. Here are the mortality hazard ratios (95% CI) associated with being in the top (vs. bottom) quintile for consumption of each fat type, after controlling for "known & suspected risk factors": ω-6 PUFA 0.81 (0.78-0.84) MUFA 0.89 (0.84-0.94) ω-3 PUFA 0.96 (0.93-1.00) Saturated 1.08 (1.03-1.14) Trans-fat 1.13 (1.07-1.18) I don't have the full text yet, so I haven't looked at the details, but it is interesting to see that omega-6 PUFA came out on top as the healthiest fat to consume. This seem to contradict the conventional (folk?) wisdom that Omega-6 PUFA is pro-inflammatory and so we shouldn't eat very much of it, at least without balancing it with sufficient Omega-3 fats (e.g. in a 3:1 ratio). Some interesting quotes from the popular press interview with one of the authors: f people replaced a mere 5% of their calorie intake from "bad" fats with polyunsaturated fats, they could reduce their risk of death by 27%. If those calories came from monounsaturated fats, the risk of mortality dropped by 13%. One reason MUFA may not have done better is the fact that a large fraction of the MUFA in the average American diet comes from animal products, which contain saturated fat along with other unhealthy components, which the researchers couldn't entirely control for: "A large proportion of food sources of monounsaturated fat in the typical American diet are animal-sourced, such as dairy and red meats," Hu said, pointing out that those are also major sources of saturated fats. "Therefore, current analysis may not be able to completely distinguish the benefits of monounsaturated fat from the effects of food source and saturated fats." The Omega-6 PUFA that was protective was, not surprisingly linoleic acid: One polyunsaturated fat, an omega-6 fatty acid called linoleic acid, was shown in the Harvard study to be especially protective against death by cancer and coronary artery disease, Hu said. Prior studies showed linoleic acid to reduce total and bad cholesterol, and to be associated with better blood pressure and insulin sensitivity. Though some studies have connected too much omega-6 with inflammation in the body, others find no such link. Linoleic acid is found in sunflower, soybean and safflower oils, as well as nuts and seeds. Walnuts, Brazil nuts and peanuts are excellent sources, as are safflower, pumpkin and squash seeds. Omega-3 Alpha-linolenic acid (e.g. from flax seeds and walnuts) wasn't protective against all-cause mortality, but does appear to be healthy for the brain, as other studies have found: Another key polyunsaturated fat, the omega-3 fatty acid called alpha-linolenic, was not associated with "all-cause mortality," Hu said, but "interestingly, we found that alpha-linolenic acid was protective against death due to neurodegenerative disease." I'd be really interested to hear Michael's take on this one, particularly the Omega-6 vs. Omega-3 finding - even if it's just an off-the-cuff remark. As Sthira mentioned yesterday in the olive oil thread, a little of Michael's insight is better than an in-depth report from him that he never has time to finish to his own satisfaction... --Dean ----------- [1] JAMA Intern Med. Published online July 05, 2016. doi:10.1001/jamainternmed.2016.2417 Association of Specific Dietary Fats With Total and Cause-Specific Mortality Dong D. Wang, MD, MSc1,3; Yanping Li, PhD1; Stephanie E. Chiuve, ScD1,2; Meir J. Stampfer, MD, DrPH1,2,3,4; JoAnn E. Manson, MD, DrPH2,3,4; Eric B. Rimm, ScD1,3,4; Walter C. Willett, MD, DrPH1,3,4; Frank B. Hu, MD, PhD1,3,4 ABSTRACT Importance Previous studies have shown distinct associations between specific dietary fat and cardiovascular disease. However, evidence on specific dietary fat and mortality remains limited and inconsistent. Objective To examine the associations of specific dietary fats with total and cause-specific mortality in 2 large ongoing cohort studies. Design, Setting, and Participants This cohort study investigated 83 349 women from the Nurses’ Health Study (July 1, 1980, to June 30, 2012) and 42 884 men from the Health Professionals Follow-up Study (February 1, 1986, to January 31, 2012) who were free of cardiovascular disease, cancer, and types 1 and 2 diabetes at baseline. Dietary fat intake was assessed at baseline and updated every 2 to 4 years. Information on mortality was obtained from systematic searches of the vital records of states and the National Death Index, supplemented by reports from family members or postal authorities. Data were analyzed from September 18, 2014, to March 27, 2016. Main Outcomes and Measures Total and cause-specific mortality. Results During 3 439 954 person-years of follow-up, 33 304 deaths were documented. After adjustment for known and suspected risk factors, dietary total fat compared with total carbohydrates was inversely associated with total mortality (hazard ratio (HR) comparing extreme quintiles, 0.84; 95% CI, 0.81-0.88; P < .001 for trend). The HRs of total mortality comparing extreme quintiles of specific dietary fats were 1.08 (95% CI, 1.03-1.14) for saturated fat, 0.81 (95% CI, 0.78-0.84) for polyunsaturated fatty acid (PUFA), 0.89 (95% CI, 0.84-0.94) for monounsaturated fatty acid (MUFA), and 1.13 (95% CI, 1.07-1.18) for trans-fat (P < .001 for trend for all). Replacing 5% of energy from saturated fats with equivalent energy from PUFA and MUFA was associated with estimated reductions in total mortality of 27% (HR, 0.73; 95% CI, 0.70-0.77) and 13% (HR, 0.87; 95% CI, 0.82-0.93), respectively. The HR for total mortality comparing extreme quintiles of ω-6 PUFA intake was 0.85 (95% CI, 0.81-0.89; P < .001 for trend). Intake of ω-6 PUFA, especially linoleic acid, was inversely associated with mortality owing to most major causes, whereas marine ω-3 PUFA intake was associated with a modestly lower total mortality (HR comparing extreme quintiles, 0.96; 95% CI, 0.93-1.00; P = .002 for trend). Conclusions and Relevance Different types of dietary fats have divergent associations with total and cause-specific mortality. These findings support current dietary recommendations to replace saturated fat and trans-fat with unsaturated fats. PMID: 27379574
  4. All, I'm usually reluctant to post studies that try to associate single nucleotide polymorphisms (SNPs) with health or longevity outcomes. There are several reasons to be skeptical of such gene studies, including: They often fail to replicate across different populations The effects of individual SNP variations are often quite small - since there are usually many genes and polymorphisms that contribute to any important health/longevity outcome Often it's not even clear from the study what the specific allele variation(s) the authors are evaluating You often can't even find out what variant of an allele you have - since only some of us have our own genetic data and even that is only partial coverage through 23andMe. There is nothing you can do about it anyway - your genes are your genes. These polymorphisms and their effects often have nothing to do with CR. But this new meta-analysis [1] posted by Al Pater (thanks Al!) seems to suffer from none of these shortcomings. It focuses on a SNP in the FoxO3 gene (rs2802292) which has been previously associated with longevity - is it overrepresented in centenarians [2], as discussed here, and summarized as: [T]he odds ratio for reaching 100 years of age for rs2802292(G;G) vs (T;T) carriers was 2.75 (p = 0.00009; adjusted p = 0.00135). One's odds of living to 100 with one copy of 'G' for rs2802292 (i.e. G:T), appears to be about 1.5-2 times greater than people with T:T. Those results were encouraging, but didn't address causality, and was limited to a homogeneous population of men. Plus it only seemed relevant for people without other 'gotchas' (genetic or otherwise) that might kill them off long before reaching 100. What about the rest of us mortals, who may not be destined to live that long? Does having copies of the 'G' allele for rs2802292 do the rest of us any good on the way to extreme longevity? Apparently - Yes! Study [1] followed three pretty large groups of Americans with Japanese (N ≈ 3600), Caucasian (N ≈ 1600), or African (N ≈ 1000) ancestory for 17 years to assess the association between SNP rs2802292 status and mortality. Interestingly, the frequency of being a lucky 'G' Allele Carrier (GAC) for this SNP varied between the three populations - 47% of Japanese, 58% of Caucasian and 92% of African ancestry folks were GACs. Across all three populations, being a GAC was associated with a 10% reduction in all-cause mortality over the 17 year follow-up, with virtually all of the benefit resulting from a 26% reduction in heart disease mortality. Here is the most important figure from the free full text: As you can see the effect was quite consistent across the three populations. The difference in the confidence interval for the three groups was a result of the different population sizes. The cool thing is that those of us with 23andMe data can find out our status for SNP rs2802292. Simply log in to 23andMe and follow this link. I'm fortunate to be in the ~60% of caucasian people who is a 'G' carrier for this allele (I've got one copy). But for anyone who isn't lucky enough to be a GAC for this allele, there is still hope. Why? Because FoxO3 gene activity is something we know quite a bit about, including ways of boosting its activity, like the G allele for rs2802292 apparently does. Curiously, cider vinegar appears to upregulate DAF-16, the C. Elegans equivalent of FoxO3, which in turn resulted in the worms living 25% longer, as discussed here. So maybe cider vinegar is worth including in one's diet. I do. But even more relevant, we know that both CR and cold exposure increase FoxO3 gene expression largely by upregulating SIRT1, as discussed recently here. So everybody wins! --Dean ------------------ [1] The FoxO3 gene and cause-specific mortality. Willcox BJ, Tranah GJ, Chen R, Morris BJ, Masaki KH, He Q, Willcox DC, Allsopp RC, Moisyadi S, Poon LW, Rodriguez B, Newman AB, Harris TB, Cummings SR, Liu Y, Parimi N, Evans DS, Davy P, Gerschenson M, Donlon TA. Aging Cell. 2016 Apr 13. doi: 10.1111/acel.12452. [Epub ahead of print] Free Article http://onlinelibrary.wiley.com/doi/10.1111/acel.12452/full http://onlinelibrary.wiley.com/doi/10.1111/acel.12452/pdf Abstract The G allele of the FOXO3 single nucleotide polymorphism (SNP) rs2802292 exhibits a consistently replicated genetic association with longevity in multiple populations worldwide. The aims of this study were to quantify the mortality risk for the longevity-associated genotype and to discover the particular cause(s) of death associated with this allele in older Americans of diverse ancestry. It involved a 17-year prospective cohort study of 3584 older American men of Japanese ancestry from the Honolulu Heart Program cohort, followed by a 17-year prospective replication study of 1595 white and 1056 black elderly individuals from the Health Aging and Body Composition cohort. The relation between FOXO3 genotype and cause-specific mortality was ascertained for major causes of death including coronary heart disease (CHD), cancer, and stroke. Age-adjusted and multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) for all-cause and cause-specific mortality. We found G allele carriers had a combined (Japanese, white, and black populations) risk reduction of 10% for total (all-cause) mortality (HR = 0.90; 95% CI, 0.84-0.95; P = 0.001). This effect size was consistent across populations and mostly contributed by 26% lower risk for CHD death (HR = 0.74; 95% CI, 0.64-0.86; P = 0.00004). No other causes of death made a significant contribution to the survival advantage for G allele carriers. In conclusion, at older age, there is a large risk reduction in mortality for G allele carriers, mostly due to lower CHD mortality. The findings support further research on FOXO3 and FoxO3 protein as potential targets for therapeutic intervention in aging-related diseases, particularly cardiovascular disease. KEYWORDS: FOXO3; heart disease; longevity; mortality PMID: 27071935 -------------- [2] Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13987-92. doi: 10.1073/pnas.0801030105. Epub 2008 Sep 2. FOXO3A genotype is strongly associated with human longevity. Willcox BJ(1), Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD. Author information: (1)Pacific Health Research Institute, 846 South Hotel Street, Honolulu, HI 96813, USA. bjwillcox@phrihawaii.org Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity. However, to date human data have been scarce. Studies have been hampered by small sample sizes, lack of precise phenotyping, and population stratification, among other challenges. Therefore, to more precisely assess potential genetic contributions to human longevity from genes linked to IIS signaling, we chose a large, homogeneous, long-lived population of men well-characterized for aging phenotypes, and we performed a nested-case control study of 5 candidate longevity genes. Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs. homozygous major alleles between the cases and controls was 2.75 (P = 0.00009; adjusted P = 0.00135). Long-lived men also presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls. Several of these aging phenotypes were associated with FOXO3A genotype. Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity and this was associated with homozygosity for the FOXO3A GG genotype. Further exploration of the FOXO3A gene, human longevity and other aging phenotypes is warranted in other populations. PMCID: PMC2544566 PMID: 18765803
  5. Low testosterone (hypogonadism), besides potentially reducing quality of life (a commonly held notion the validity of which many of us male CR folks would contend...), has been thought to be potentially associated with increased mortality, particularly from cardiovascular disease, at least among the general (non-CR) population. Here again is a situation where we hope that our low testosterone (as frequently but not universally experienced by CR men) has different health/longevity implications than hypogonadism in the general population, where it is frequently associated with obesity and other indicators of ill-health. Well, this study posted by Al Pater (thanks Al!) from the Framingham Heart Study may help ease those doubts and concerns. It found that even in a general population of 254 elderly men (avg age 75), neither low testosterone nor absolute level or change in other sex hormones were associated with increased mortality at either 5 or 10 year follow-up, once other confounding factors were statistically factored out. The confounders they corrected for were age, body mass index, smoking, total cholesterol, high-density lipoprotein cholesterol, type 2 diabetes, systolic blood pressure, and antihypertensive medication - all of which seem reasonable to factor out. To quote from the discussion of the free full text: Leveraging the unique data set and design of the community-based FHS, the present study is the first to investigate longitudinal trajectory patterns of serial sex steroid and gonadotropins measurements and their associations with 5-year and 10-year risk of incident clinical CVD and all-cause mortality. We observed no consistent association of sex steroids, gonadotropins, and their trajectories with incident clinical CVD or all-cause mortality risk in 254 elderly men in the community. In other words, it appears that if you are a healthy elderly man (i.e. without the confounders listed above, which hopefully most CR folks do/will avoid), having low testosterone is not associated with an increased risk of cardiovascular disease or overall mortality. So we've got that goin' for us... --Dean ----------- [1] Association of sex steroids, gonadotrophins, and their trajectories with clinical cardiovascular disease and all-cause mortality in elderly men from the Framingham Heart Study. Haring R, Teng Z, Xanthakis V, Coviello A, Sullivan L, Bhasin S, Murabito JM, Wallaschofski H, Vasan RS. Clin Endocrinol (Oxf). 2013 Apr;78(4):629-34. doi: 10.1111/cen.12013. PMID: 22901104 Free PMC Article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161203/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161203/pdf/nihms622794.pdf Abstract BACKGROUND: Emerging data from longitudinal studies suggest that low sex steroid concentrations in men are associated with increased cardiovascular risk and mortality. The impact of longitudinal trajectory patterns from serial sex steroid and gonadotrophin measurements on the observed associations is unknown to date. METHODS: We prospectively evaluated 254 elderly men (mean age, 75·5 years) of the Framingham Heart Study with up to four serial measurements of serum total testosterone (TT), dehydroepiandrosterone sulphate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total estradiol (EST); and constructed age- and multivariable-adjusted Cox proportional hazard regression models relating baseline hormone concentrations and their mean, slope and variation over time (modelled as continuous and categorized into quartiles) to the incidence of clinical cardiovascular disease (CVD) and all-cause mortality at 5- and 10-year follow-up. RESULTS: We observed no association between baseline concentrations of sex steroids, gonadotrophins and their trajectories with incident clinical CVD over 5- and 10-year follow-up. Although higher baseline TT concentrations were associated with lower mortality risk at 5 years (hazard ratio per quartile increment, 0·74; 95% confidence interval, 0·56-0·98), correction for multiple statistical testing (P < 0·005) rendered this association statistically nonsignificant. Repeat analyses at the 10-year follow-up time point also demonstrated no significant association between sex steroids, gonadotrophins or their trajectories and mortality. CONCLUSION: Investigating longitudinal trajectory patterns of serial sex steroid and gonadotrophin measurements, the present study found no consistent associations with incident clinical CVD and all-cause mortality risk in elderly men from the community.
  6. Dean Pomerleau

    Nuts and Mortality

    Al Pater posted the following prospective study [1] (thanks Al!) on the association between nut intake and mortality amongst a group of 20,000 middle aged Italians. It found that compared with people who didn't consume nuts, people who consumed them more than 8 times per month had about a 50% reduction in all-cause mortality risk during the 4 years of followup, largely due to reduced cancer risk. They found the nut eaters also had lower levels of inflammation. Not surprisingly, nut consumption was more beneficial for those who otherwise didn't adhere to a Mediterranean diet. More evidence that nuts are a very healthy food! --Dean ------------- [1] Br J Nutr. 2015 Sep;114(5):804-11. doi: 10.1017/S0007114515002378. Nut consumption is inversely associated with both cancer and total mortality in a Mediterranean population: prospective results from the Moli-sani study. Bonaccio M(1), Di Castelnuovo A(1), De Curtis A(1), Costanzo S(1), Bracone F(1), Persichillo M(1), Donati MB(1), de Gaetano G(1), Iacoviello L(1). Author information: (1)1Department of Epidemiology and Prevention,IRCCS Istituto Neurologico Mediterraneo,Neuromed,86077 Pozzilli,Isernia,Italy. Nut intake has been associated with reduced inflammatory status and lower risk of CVD and mortality. The aim of this study was to examine the relationship between nut consumption and mortality and the role of inflammation. We conducted a population-based prospective investigation on 19 386 subjects enrolled in the Moli-sani study. Food intake was recorded by the Italian version of the European Project Investigation into Cancer and Nutrition FFQ. C-reactive protein, leucocyte and platelet counts and the neutrophil:lymphocyte ratio were used as biomarkers of low-grade inflammation. Hazard ratios (HR) were calculated using multivariable Cox proportional hazard models. During a median follow-up of 4·3 years, 334 all-cause deaths occurred. As compared with subjects who never ate nuts, rare intake (≤2 times/month) was inversely associated with mortality (multivariable HR=0·68; 95 % CI 0·54, 0·87). At intake ≥8 times/month, a greater protection was observed (HR=0·53; 0·32, 0·90). Nut intake (v. no intake) conveyed a higher protection to individuals poorly adhering to the Mediterranean diet (MD). A significant reduction in cancer deaths (HR=0·64; 95 % CI 0·44, 0·94) was also observed, whereas the impact on CVD deaths was limited to an inverse, but not significant, trend. Biomarkers of low-grade inflammation were reduced in nut consumers but did not account for the association with mortality. In conclusion, nut intake was associated with reduced cancer and total mortality. The protection was stronger in individuals with lower adherence to MD, whereas it was similar in high-risk groups (diabetics, obese, smokers or those with the metabolic syndrome), as compared with low-risk subjects. Inflammation did not explain the observed relationship. PMID: 26313936 [PubMed - in process]
  7. All, Loneliness and social support are things we don't talk about much around here and (speaking for myself) are things we may not pay enough attention to in general, both for their direct impact on quality of life (i.e. social engagements are an important part of what makes life worth living for many people), and for their instrumental benefits (i.e. loneliness and one's social network size seem to have a pretty dramatic impact on longevity). Regarding this second, instrumental benefit of a strong social network on longevity, I found that there are several recent studies similar to [1]. It followed 600 men and women who were 70+ at baseline for 18 years, measuring at several time points their self-reported loneliness (i.e. how frequently a person feels lonely) and their social network, which was characterized as follows: ocial networks were measured by using four separate indicators including: marital status (married = 1, unmarried = 0), number of children, contact frequency with children and with friends, with scores ranging from 0 (do not meet at all) to 4 (almost everyday), and household size (number of people residing with the respondent). What they found regarding self-reported loneliness was: Mortality was higher among lonely men compared to those who were not lonely (46.9% and 34.3%, respectively) and among lonely women (58% and 48.4%, respectively). Here are the four survival curves for lonely/not-lonely men/women over the 18 years of followup from the full text: As you can see, women outlived men (no surprise) and both lonely men and women died significantly sooner than their not-lonely peers. Regarding the impact of one's social network on mortality, they found: [T]he variables that were found to significantly predict mortality among men were health status (self-rated health and co-morbidity), functional status (ADL), and social variables (marital status and size of household), suggesting that mortality was higher among those who were in poorer health and impaired functional status, were unmarried, and lived in smaller households. Among women only economic status was found to significantly predict mortality, suggesting that mortality was higher among poorer women. In short, for men in particular, a feeling of loneliness, being unmarried and living alone appear to be predictors of early mortality. These results raise two questions in my mind: 1) How and to what extent does the practice of CR impact one's social network and feeling of loneliness? Given that some of us eat strict and unusual diets, and eat at unusual times/intervals, it seems pretty plausible that this could (and in fact does, in my case) serve to isolate us to some degree from family and friends, who typically don't follow the same dietary habits. Eating together serves such an important social function in all cultures, it would seem almost inevitable that eating differently will impact one's relationship with others. Such an increase in social isolation could lead to loneliness, and the possibility of increased mortality - perhaps even negating the longevity benefits of CR. On the flip side, I'm pretty convinced from personal experience that CR can contribute to increased psychological resilience and a sense of well-being, which could counterbalance the negative influence of increased social isolation and reduce one's sense of loneliness. 2) To what extent can 'virtual' social networks, like connecting with other CR practitioners on this forum, make up for lack of direct social contact and reduce feelings of loneliness. Over the years I've found engaging with other folks from the CR Society through these forums and before that the CR mailing list, to be quite psychologically rewarding, producing a feeling of camaraderie,social connectedness, and a sense of being helpful to others, that would seem to me to be potentially beneficial substitute for direct face-to-face social connects. But I've never really been a very social person (e.g. I've always felt uncomfortable at parties), and so may be somewhat biased in this regard. I'd be interested in engaging with others on this topic and hearing what you think the net impact CR has had on your social network and feelings of loneliness vs. connectedness. --Dean Note: I debated whether to post this to "General Health & Longevity" or "CR Practice". I'm starting it in General Health & Longevity, since in general loneliness had nothing directly to do with CR. But I'm hoping others will engage in a discussion of how CR impacts one's social life and feeling of loneliness, in which case I'll move the thread to "CR Practice". ----------- [1] Int J Aging Hum Dev. 2011;72(3):243-63. Loneliness, social networks, and mortality: 18 years of follow-up. Iecovich E(1), Jacobs JM, Stessman J. Full Text via Sci-hub.io: http://ahd.sagepub.com.sci-hub.io/content/72/3/243.short We examined the influence of changes in loneliness and social support networks upon mortality during 18 years of follow-up among an elderly cohort and determined the gender-specific nature of this relationship. The study is based on data collected from the Jerusalem Longitudinal Study (1990-2008), which has followed a representative sample of 605 community-dwelling elderly people. Subjects were randomly selected from an age homogenous cohort born 1920-1921 and were aged 70, 78, and 85 when data were collected at baseline in 1990 and at follow-up in 1998 and 2005. All-cause mortality from age 70-88 was determined according to the National Death Registry. Sense of loneliness was found to be stable among the majority of the respondents. Loneliness among men was found in bivariate analyses to be a risk factor for mortality. Although multivariate analyses found that loneliness was not a significant predictor of mortality, nonetheless several social network factors (marital status at the baseline and living arrangements) were found to predict mortality among men. Loneliness and solitude among elderly men can be a risk factor of mortality. The findings imply that attention should be given to this high risk group. PMID: 21834390
  8. I don't usually post about the benefits of getting the RDA of specific micronutrients. It should be a no-brainer by now that people should run their diet through nutrition tracking software like CRON-O-Meter to make sure they aren't deficient in essential micronutrients. But this large new cohort study [1], posted by Al Pater to the email list (thanks Al!), found such a big benefit from higher intake of selenium (Se) that I thought it worth posting about. In [1], the researchers followed 133,000+ adult (40-75 years old) men and women for an average 8-13 years, during which time about 10,000 of them died. They looked at their likelihood of dying from CVD, cancer and all-causes based on what quintile of selenium intake they were in. What they found was pretty striking. While (surprisingly - given previous results) Se intake didn't make any difference for cancer mortality, for both CVD and all-cause mortality there was a strong inverse association between Se intake and mortality. In particular men and women in the highest quintile of Se intake were about 20% less likely to die of any cause, and men were 33% less likely to die of CVD, even after statistical adjustment for all the usual potential confounders. How much Se was the highest quintile consuming? The average intake of men in the highest quintile was 70 mcg/day, a bit higher than the US RDA of 55 mcg/day, compared with about 27 mcg/day in the lowest quintile, which is about 1/2 the US RDA. The mortality results displayed a dose-response relationship across the quintiles, making the trend quite significant (p for trend = 0.0001): The corresponding HR among men were 1·00 (reference), 0·91 (95 % CI 0·83, 0·99), 0·86 (95 % CI 0·78, 0·95), 0·82 (95 % CI 0·73, 0·91) and 0·79 (95 % CI 0·70, 0·89), respectively (P=0·0001 for trend across categories). The discussion section is quite interesting and important. In it, the authors put their results into the context of previous studies involving selenium. They cite several prospective cohort studies which found similar results, namely higher baseline selenium intake or plasma levels were associated with lower mortality. But interestingly, they say several intervention trials have not observed mortality benefits from selenium supplements, either alone or in combination with other supplemental micronutrients: Although a meta-analysis of observational studies showed a significant inverse association between Se concentration and risk of CHD (ref), randomized trials using Se in combination with other antioxidants have not shown a significant protective effect on CVD or mortality (ref, ref). However, most of these large prevention trials did not consider baseline nutrition level in their inclusion criteria and Se was given in combination with other vitamins and minerals in all but two trials (ref,ref). In short, the authors are suggesting that too much selenium (i.e. too much above the RDA), or selenium in supplement form or in combination with other supplemental micronutrients, might not be so good - hence the discrepancy between their results and intervention trials. This seems to suggest it may be important to get one's RDA of selenium, but not too much more. So don't go overboard on those brazil nuts - half of one nut per day should be sufficient, or if you'd rather not play roulette with your selenium intake, you might consider a supplement rather than a fraction of a brazil nut. --Dean ------- [1] Public Health Nutr. 2016 May 20:1-8. [Epub ahead of print] Dietary selenium intake and mortality in two population-based cohort studies of 133 957 Chinese men and women. Sun JW, Shu XO, Li HL, Zhang W, Gao J, Zhao LG, Zheng W, Xiang YB. http://journals.cambridge.org/action/displayFulltext?type=6&fid=10330859&jid=PHN&volumeId=-1&issueId=-1&aid=10330858&bodyId=&membershipNumber=&societyETOCSession=&fulltextType=RA&fileId=S1368980016001130 http://journals.cambridge.org/download.php?file=%2FPHN%2FS1368980016001130a.pdf&code=34f12fd0563e386fd563057d88374391 Abstract OBJECTIVE: To investigate the potential influence of dietary Se intake on mortality among Chinese populations. DESIGN: We prospectively evaluated all-cause, CVD and cancer mortality risks associated with dietary Se intake in participants of the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health study (SMHS). Dietary Se intake was assessed by validated FFQ during in-person interviews. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % CI. SETTING: Urban city in China. SUBJECTS: Chinese adults (n 133 957). RESULTS: During an average follow-up of 13.90 years in the SWHS and 8.37 years in the SMHS, 5749 women and 4217 men died. The mean estimated dietary Se intake was 45.48 ?g/d for women and 51.34 ?g/d for men, respectively. Dietary Se intake was inversely associated with all-cause mortality and CVD mortality in both women and men, with respective HR for the highest compared with the lowest quintile being 0.79 (95 % CI 0.71, 0.88; P trend<0.0001) and 0.80 (95 % CI 0.66, 0.98; P trend=0.0268) for women, and 0.79 (95 % CI 0.70, 0.89; P trend=0.0001) and 0.66 (95 % CI 0.54, 0.82; P trend=0.0002) for men. No significant associations were observed for cancer mortality in both women and men. Results were similar in subgroup and sensitivity analyses. CONCLUSIONS: Dietary Se intake was inversely associated with all-cause and cardiovascular mortality in both sexes, but not cancer mortality. KEYWORDS: China; Dietary; Mortality; Prospective study; Selenium intake PMID: 27197889
  9. "Mediterranean diet ... in [high risk] individuals ... associations with all-cause (HR = 1.02; 95 % CI 0.90-1.15) and CV mortality (0.94; 95 % CI 0.76-1.15) were not significant." Predictive role of the Mediterranean diet on mortality in individuals at low cardiovascular risk: a 12-year follow-up population-based cohort study. Bo S, Ponzo V, Goitre I, Fadda M, Pezzana A, Beccuti G, Gambino R, Cassader M, Soldati L, Broglio F. J Transl Med. 2016 Apr 12;14(1):91. doi: 10.1186/s12967-016-0851-7. PMID: 27071746 Free Article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830057/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830057/pdf/12967_2016_Article_851.pdf Abstract BACKGROUND: Adherence to the Mediterranean diet reduces the risk of all-cause and cardiovascular (CV) mortality and the incidence of CV events. However, most previous studies were performed in high-risk individuals. Our objective was to assess whether the adherence to the Mediterranean diet, evaluated by the MED score, was associated with all-cause and CV mortality and incidence of CV events in individuals at low CV risk from a population-based cohort, after a 12-year mean follow-up. METHODS: A cohort of 1658 individuals completed a validated food-frequency questionnaire in 2001-2003. The MED score was calculated by a 0-9 scale. Anthropometric, laboratory measurements, and the vital status were collected at baseline and during 2014. The baseline CV risk was estimated by the Framingham risk score. Participants were divided into two groups: individuals at low risk (CV < 10) and individuals with CV risk =/>10. RESULTS: During a 12-year mean follow-up, 220 deaths, 84 due to CV diseases, and 125 incident CV events occurred. The adherence to the Mediterranean diet was low in 768 (score 0-2), medium in 685 (score 4-5) and high in 205 (score >6) individuals. Values of BMI, waist circumference, fasting glucose and insulin significantly decreased from low to high diet adherence only in participants with CV risk =/>10. In a Cox-regression model, the hazard ratios (HRs) in low-risk individuals per unit of MED score were: HR = 0.83 (95 % CI 0.72-0.96) for all-cause mortality, HR = 0.75 (95 % CI 0.58-0.96) for CV mortality, and HR = 0.79 (95 % CI 0.65-0.97) for CV events, after multiple adjustments. In individuals with CV risk =/>10, the MED score predicted incident CV events (HR = 0.85; 95 % CI 0.72-0.99), while the associations with all-cause (HR = 1.02; 95 % CI 0.90-1.15) and CV mortality (0.94; 95 % CI 0.76-1.15) were not significant. CONCLUSIONS: Greater adherence to the Mediterranean diet was associated with reduced fatal and non fatal CV events, especially in individuals at low CV risk, thus suggesting the usefulness of promoting this nutritional pattern in particular in healthier individuals. KEYWORDS: All-cause mortality; Cardiovascular mortality; Cardiovascular risk; Mediterranean diet
  10. Sthira

    Radiolab labs on mortality

    Good stuff, listened here yet? http://www.radiolab.org/story/91562-mortality/ I'd review it and tease it out like Dean does so much service here for us, but I'm not as eloquent as Dean, don't have his style and time, and I'd rather hear your thoughts and comments than my own silliness. "This hour of Radiolab: is death a disease that can be cured? "We filter the modern search for the fountain of youth through personal stories of witnessing death -- the death of a cell, the death of a loved one...and the aging of a society."
  11. Al Pater posted this review article [1] from way back in 2002 on the question of whether or not worldwide life expectancy is really beginning to level off, or is marching higher at the same 1/4 of a year per year rate that it has for the last 150 years. Here are two graphs from the paper, the first showing how striking and consistent the trend towards a higher lifespan has been, and how virtually everyone predicts it is going to level off (dashed red lines at the top): The authors postulate that the impression people have that lifespan is constantly on the verge of plateauing is an illusion with a few different causes. One interesting one is political. Politicians tend to low-ball when it comes to estimating future gains in life expectancy to make the cost of social programs, particularly those directly at the elderly like social security, medicare, look less costly and burdensome on the future. More interestingly, and with more evidence it would seem, they suggest the apparent leveling off in life expectancy gains is a result of the fact that the leading nation in life expectancy improvements keeps changing, with some countries (like the US) falling off the cutting edge, while other countries, like Japan, pick up the torch and push life expectancy higher at the same old rate of 1/4 of a year per year. So for the citizen in most countries, they fact is that lie expectancy improvements have levelled off. They give as evidence for this effect this graph: As you can see, Japan comes up after WWII to overtake the rest of the world in life expectancy, and keep us on the linear curve of life expectancy increases. Here are the authors' three rather bold assertions in the concluding paragraph of the paper: This mortality research has exposed the empirical misconceptions and specious theories that underlie the pernicious belief that the expectation of life cannot rise much further. Nonetheless, faith in proximate longevity limits endures, sustained by ex cathedra pronouncement and mutual citation (1, 8, 9). In this article we add three further lines of cogent evidence. First, experts have repeatedly asserted that life expectancy is approaching a ceiling: these experts have repeatedly been proven wrong. Second, the apparent leveling off of life expectancy in various countries is an artifact of laggards catching up and leaders falling behind. Third, if life expectancy were close to a maximum, then the increase in the record expectation of life should be slowing. It is not. For 160 years, best-performance life expectancy has steadily increased by a quarter of a year per year, an extraordinary constancy of human achievement. As I said - bold words. So that was in 2002. It's been almost a decade and a half since the paper was written. Have gains in life expectancy continued their "steadily increased by a quarter of a year per year" that the authors observe happening for the last 160 years? Nope - Not quite at least. Japan remains #1, and here is a graph of Japanese life expectancy that includes the period between 2002 through 2014: The paper reports in 2002 the life expectancy of a Japanese female was "almost 85 years", and in 2014 it was almost 87 years. So that is a life expectancy increase of 2 years in 12 years, or one sixth of a year per year, rather than the quarter of a year per year trend the authors point to. That equates to an average yearly shortfall in lifespan gains of 33% relative to the authors' prediction. Of course, this may be just a short-term deviation away from the long-term trend. Perhaps new advances in treatments or therapies for the diseases of aging (e.g. stem cell therapy, CRISPR-based gene therapy) will come along and keep us on the curve. It reminds me of the supposedly inexorable Moore's Law that futurist and immortality-optimist Ray Kurzweil likes to point to, namely that computer power (actually transistor count) doubles every two years, like clockwork, and has been for at least the last 40-50 years, and much longer than that if you ask Kurzweil. Unfortunately, I looks like we're falling off that curve too, according to this recent article in Nature (Feb '16): Next month, the worldwide semiconductor industry will formally acknowledge what has become increasingly obvious to everyone involved: Moore's law, the principle that has powered the information-technology revolution since the 1960s, is nearing its end. Similarly, at this point we seem to be slowing down rather than speeding up increases in life expectancy which would move us toward longevity escape velocity, where life expectancy increases by (at least) one year per year. --Dean ---------- [1] Science. 2002 May 10;296(5570):1029-31. No abstract available. Demography. Broken limits to life expectancy. Oeppen J, Vaupel JW. Free Full text: http://www.econ.ku.dk/okocg/VV/VV-Economic%20Growth/articles/artikler-2006/Broken-limits-to-life-expectancy.pdf Summary Is human life expectancy approaching its limit? Many--including individuals planning their retirement and officials responsible for health and social policy--believe it is, but the evidence presented in the Policy Forum suggests otherwise. For 160 years, best-performance life expectancy has steadily increased by a quarter of a year per year, an extraordinary constancy of human achievement. Mortality experts have repeatedly asserted that life expectancy is close to an ultimate ceiling; these experts have repeatedly been proven wrong. The apparent leveling off of life expectancy in various countries is an artifact of laggards catching up and leaders falling behind. PMID: 12004104
  12. All, There is a new study [1] out this week getting lots of media attention with headlines like Study: Obesity more dangerous to health than lack of fitness and 'Fat but fit' counts for nothing scientists say. After reading the full text (via sci-hub.io) it appears this is a gross oversimplification, if not outright distortion of what the study really says. In the study, researchers looked at the aerobic fitness and weight of 1.3 million Swedish men at the time of their military conscription (mean age 18). Aerobic fitness was tested by seeing how long the men could keep pedalling on a stationary bike whose resistance was increased at a rate of 2.5 watts/min. The subjects were then followed for an average of 29 years (to around age 47 - so still relatively young), during which 44K of them died. They then compiled statistics about mortality rate as a function of both baseline weight and baseline aerobic fitness. The results of the entire study are nicely summarized in a single graph (don't you love it when that happens?!). Here it is: There are several interesting things that can be gleaned from this graph: Being more aerobically fit resulted in reduced mortality across all four BMI categories. There was virtually no difference in the mortality rate of men with low BMI (< 18.5) vs. normal BMI (18.5 - 25). The fact that the researchers did not correct for smoking would seem to make this lack of difference even more significant, since it is likely that the skinny group smoked more than the normal weight group, and so would be expected to have a higher mortality rate, based on many other studies. The most fit obese men were significantly more likely to die than the least fit normal or even overweight individuals. It is only the last of these three points which seem to have sparked all the media attention. But as you can see, the study has much more interesting information than just that, particularly for us CR practitioners - namely that when it comes to reducing mid-life mortality, being skinny isn't bad and being more aerobically fit is good. --Dean --------- [1] International Journal of Epidemiology, 2015, 1–10 doi: 10.1093/ije/dyv321 Aerobic fitness in late adolescence and the risk of early death: a prospective cohort study of 1.3 million Swedish men Gabriel Hogstrom, Anna Nordstrom and Peter Nordstrom Full text (via sci-hub.io): http://ije.oxfordjournals.org.sci-hub.io/content/early/2015/12/20/ije.dyv321.full Abstract Background: Fitness level and obesity have been associated with death in older populations. We investigated the relationship between aerobic fitness in late adolescence and early death, and whether a high fitness level can compensate the risk of being obese. Methods: The cohort comprised 1 317 713 Swedish men (mean age, 18 years) that conscripted between 1969 and 1996. Aerobic fitness was assessed by an electrically braked cycle test. All-cause and specific causes of death were tracked using national registers. Multivariable adjusted associations were tested using Cox regression models. Results: During a mean follow-up period of 29 years, 44 301 subjects died. Individuals in the highest fifth of aerobic fitness were at lower risk of death from any cause [hazard ratio (HR), 0.49; 95% confidence interval (CI), 0.47–0.51] in comparison with individuals in the lowest fifth, with the strongest association seen for death related to alcohol and narcotics abuse (HR, 0.20; 95% CI, 0.15–0.26). Similar risks were found for weight-adjusted aerobic fitness. Aerobic fitness was associated with a reduced risk of death from any cause in normalweight and overweight individuals, whereas the benefits were reduced in obese individuals (P< 0.001 for interaction). Furthermore, unfit normal-weight individuals had 30% lower risk of death from any cause (HR, 0.70; 95% CI, 0.53–0.92) than did fit obese individuals. Conclusions: Low aerobic fitness in late adolescence is associated with an increased risk of early death. Furthermore, the risk of early death was higher in fit obese individuals than in unfit normal-weight individuals. Key words: Fitness, obesity, death PMID: 26686843
  13. All, Testosterone (T) and other sex hormone levels have always been a topic of interest and concern to CR practitioners. Some men (like me) report dramatically reduced T levels, down to levels not typically seen in any men except the very elderly. Others seem to maintain their T at fairly normal levels for their age. So which is better? On the one hand, low testosterone has sometimes been considered a CR "badge of courage" (among men anyway) - indicating one is practicing serious CR, and a positive reflection of the body trading off fecundity for upregulation of maintenance & repair functions (similar to low IGF-1). Women live longer than men across cultures, which some attribute to differences in T level, and eunuchs have been found to live longer, by as much as 15-20 years [2]! On the other hand, low T often (but not always) has a dramatic effect on libido, and one's overall aggressive drive to succeed / accomplish things. On the health side, negative health outcomes are frequently associated with hypogonadism (low T) in men, including bone health issues [4], sarcopenia [4], cognitive decline [5], and an increased risk of cardiovascular disease. Regarding the latter, some studies (e.g. see [3] for review) have found T supplementation in hypogonadal men reduces cardiovascular disease risk, but the effect may be limited to obese men with metabolic syndrome, or may result from pharmaceutical industry bias in T supplementation trials [6]. Interestingly, this meta-analysis [6] found that in trials not sponsored by Big Pharma, CVD risk was increased among men receiving supplemental T (OR 2.06, 95% CI 1.34 to 3.17). So overall, the relationship between the low T that many serious male CR practitioners exhibit and our long-term health & longevity remains an open question. Moreover, hypogonadism in the general population is typically associated with obesity and metabolic syndrome, obviously a very different etiology than hypogonadism in CR practitioners, making the picture even more muddled... So I reacted with interest, but also some trepidation, when I saw Al Pater post this new study [1] (thanks Al!), on the association of T and other sex hormones with all-cause, cancer and cardiovascular mortality in men. So let's dive in. First off, this was not a supplementation trial - they measured the natural levels of T, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Sex Hormone Binding Globulin (SHBG), free testosterone (FT), and estradiol (E) and in 5300 men of all ages and followed them for an average of 18.5 years to see how many died, from what causes, and how their deaths were associated with these sex hormones. Here are some interesting statistics at baseline, from the free full text Table 1 (see below): As expected, T and FT was lower in older men, whereas LH, FSH, and SHBG increased. Interestingly, smokers had higher T, FT, LH, FSH, E and SHBG than non-smokers at baseline. Exercise, and particular "competitive sport" participation, was associated with increased T, FT, and lower LH. Could be reverse causality - people with high T are more aggressive and therefore more likely to be attracted to competitive sports... Overweight and obese men had dramatically lower T and FT at baseline - which will be important later. Here is the baseline data for sex hormones by demographics for anyone interested in the details (click to enlarge): Now the interesting part - the mortality results (some of which comes from the text of the supplemental material). First for cancer mortality: There was a between-quartile trend towards increased cancer mortality with higher T, but the differences was only really significant in smokers in the highest quartile of T (OR 1.53, 95%CI: 1.14 – 2.08). In non-smokers, T and FT had virtually no impact on cancer mortality. But there was a pretty strong trend towards more cancer with higher levels of LH and FSH. Keep an eye on LH in particular, it will be important later... And now, CVD mortality: Men with total testosterone levels in the highest quartile had a reduced risk of CVD mortality compared to men in the lowest quartile (HR 0.72, 95% CI: 0.53– 0.98). The same relationship held for FT. It is looking bad for us hypogonadal CRers... But this increased CVD risk with low T (and FT) was in the fully-adjusted model, which included factoring out BMI from the analysis (recall overweight/obese men had dramatically lower T and FT at baseline). In a model that adjusted for waist circumference instead of BMI, and especially in a model that adjusted for # of markers of metabolic syndrome, the increased risk of CVD with lower T and FT dropped dramatically to the point of no longer being significant between the highest and lowest quintiles of T = (OR 0.66, 95%CI: 0.38-1.16). In other words, to first approximations, if you ignore low T and FT resulting from (or associated with) metabolic syndrome, the association between low T (and FT) and increased CVD goes away... And now, the all-important All-cause mortality: There was no significant differences in all-cause mortality across age-standardized quartiles of T (OR 1.01, 95%CI: 0.87-1.18) - to some degree higher cancer risk and lower CVD risk with higher T offset each other, so all-cause mortality was a wash with higher T. The same lack of significant mortality effect was seen for inter-quartile comparison of FT (OR 0.87, 95%CI: 0.75-1.00), but when the trend from lowest to highest quartile of FT was considered, lower FT was associated with increased all-cause mortality (p for trend < 0.02). Again, looking (somewhat) bad for hypogonadal CRers... An increased all-cause mortality was seen for men in the highest (vs. lowest) quartiles of LH and estradiol, (HR 1.32, 95% CI: 1.14 –1.53) and (HR 1.23, 95% CI: 1.06 –1.43), respectively. If you are confused by now, perhaps this graphical depiction of the major study findings for all-cause and CVD mortality (with my color highlights) will help (click to enlarge): As you can see, if we focus on all-cause mortality, higher SHBG, higher LH, and lower FT are associated with increased risk. So what the heck does all this mean?!?! Here is my take on it, basically paraphrasing the authors' discussion / speculation. Obesity, and especially metabolic syndrome, are associated with increased mortality risk, and reduced T and FT levels. It may therefore be that low T (& FT) is a marker for impaired androgen signalling in men with metabolic syndrome - i.e. their sex-hormone signalling is messed up, just like some of their other pathways (e.g. insulin signalling) are messed up by all the fat they are carrying. As a result, their LH is elevated - i.e. the "captain" is asking (via increased LH) the "engine room" (i.e. Leydig cells) to produce more T, but the Leydig cells aren't up to the task perhaps because they are gummed up with fat, so T remains low despite elevated LH calling for more. This could be similar in some respects to diabetes, in which insulin doesn't work to clear glucose because of fat so the body calls for the pancreas to produce more, and eventually the beta cells in the pancreas give up the ghost and can't make enough insulin to clear blood glucose. So what does this mean for CR practitioners? In us, T is low on purpose from the body's perspective (if I may speak teleologically) - as indicated by our low LH levels (my bloodwork shows my LH to always be near or below the low end of the RR since starting CR). In other words, rather than T being low because the body can't/won't make it (as is the case in guys with metabolic syndrome), our T is low because our body doesn't need or want it. Again it is perhaps a story similar to IGF-1 and insulin. We (hopefully) have low fasting insulin not because our beta cells are messed up and can't make it (like in late-stage diabetes resulting from metabolic syndrome), but because our bodies don't need/want much insulin - we've got enough insulin to clear the modest amount of glucose we have to process, especially since our insulin sensitivity remains high. So in short, our low T and low FT may reflect an entirely different, (hopefully) healthier state to be in than having low T and FT as a result of metabolic syndrome. But then again, that might be just wishful thinking. In particular, our low T and FT may be "intentional" on the part of our body and it may not be good for us in the long run. In other words, our bodies may be hunkering down to survive the (self-induced) famine by lowering T and FT, but in the process sacrificing "non-critical" systems like muscle mass, bone health, and cognitive function - systems that apparently benefit downstream from higher levels of testosterone. It seems it could go either way. But in any case, we're unlikely to be in as bad shape along these dimensions as men who have low T and FT as a result of metabolic syndrome. I hope this has done more to clarify than confuse. But re-reading, I'm not so sure... --Dean ---------- [1] J Clin Endocrinol Metab. 2015 Oct 21:jc20152460. [Epub ahead of print] The association of reproductive hormone levels and all-cause, cancer and cardiovascular disease mortality in men. Agergaard Holmboe S, Vradi E, Kold Jensen T, Linneberg A, Husemoen LL, Scheike T, Skakkebæk NE, Juul A, Andersson AM. Full Text: http://press.endocrine.org/doi/pdf/10.1210/jc.2015-2460 Abstract CONTEXT: Testosterone levels (T) have been associated with mortality, but controversy exists. OBJECTIVE: To investigate associations between serum levels of total testosterone, SHBG, free testosterone, estradiol, LH and FSH, and subsequent mortality with up to 30 years of follow-up. DESIGN: A prospective cohort study consisting of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with complete registry follow-up. SETTING AND PARTICIPANTS: 5,350 randomly selected men from the general population aged 30, 40, 50, 60 or 70 years at baseline. MAIN OUTCOME MEASURES: All-cause mortality, cardiovascular disease (CVD) mortality and cancer mortality. RESULTS: 1,533 men died during the follow-up period; 428 from CVD and 480 from cancer. Cox proportional hazard models revealed that men in highest LH quartile had an increased all-cause mortality compared to lowest quartile (HR=1.32, 95%CI: 1.14 to 1.53). Likewise, increased quartiles of LH/T and estradiol increased the risk of all-cause mortality (HR=1.23, 95%CI: 1.06 to 1.43, HR=1.23, 95%CI: 1.06 to 1.43). No association to testosterone levels was found. Higher LH levels were associated with increased cancer mortality (HR=1.42, 95%CI: 1.10 to 1.84) independently of smoking status. Lower CVD mortality was seen for men with testosterone in the highest quartile compared to lowest (HR=0.72, 95%CI: 0.53 to 0.98). Furthermore, negative trends were seen for SHBG and free testosterone in relation to CVD mortality, however insignificant. CONCLUSION: The observed positive association of LH and LH/T, but not testosterone, with all-cause mortality suggests that a compensated impaired Leydig cell function may be a risk factor for death by all causes in men. Our findings underpin the clinical importance of including LH measurement in the diagnostic work-up of male patients seeking help for possible androgen insufficiency. PMID: 26488309 ------------ [2] Curr Biol. 2012 Sep 25;22(18):R792-3. doi: 10.1016/j.cub.2012.06.036. The lifespan of Korean eunuchs. Min KJ, Lee CK, Park HN. Free Full Text: http://www.cell.com/current-biology/abstract/S0960-9822(12)00712-9 Abstract Although many studies have shown that there are trade-offs between longevity and reproduction, whether such trade-offs exist in humans has been a matter of debate [1,2] . In many species, including humans, males live shorter than females, which could be due to the action of male sex hormones. Castration, which removes the source of male sex hormones, prolongs male lifespan in many animals, but this issue has been debated in humans [3] . To examine the effects of castration on longevity, we analyzed the lifespan of historical Korean eunuchs. Korean eunuchs preserved their lineage by adopting castrated boys. We studied the genealogy records of Korean eunuchs and determined the lifespan of 81 eunuchs. The average lifespan of eunuchs was 70.0 ± 1.76 years, which was 14.4–19.1 years longer than the lifespan of non-castrated men of similar socio-economic status. Our study supports the idea that male sex hormones decrease the lifespan of men. PMID: 23017989 -------------- [3] Expert Opin Drug Saf. 2014 Oct;13(10):1327-51. doi: 10.1517/14740338.2014.950653. Epub 2014 Aug 19. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Corona G(1), Maseroli E, Rastrelli G, Isidori AM, Sforza A, Mannucci E, Maggi M. Author information: (1)Azienda-Usl Bologna, Maggiore-Bellaria Hospital, Medical Department, Endocrinology Unit , Bologna , Italy. INTRODUCTION: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events. AREAS COVERED: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed. EXPERT OPINION: The present systematic review and meta-analysis does not support a causal role between TS and adverse CV events. Our results are in agreement with a large body of literature from the last 20 years supporting TS of hypogonadal men as a valuable strategy in improving a patient's metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease. PMID: 25139126 --------------- [4] Clin Endocrinol (Oxf). 2005 Sep;63(3):280-93. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Isidori AM(1), Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Author information: (1)Cattedra di Andrologia, Universita 'La Sapienza', Rome, Italy. andrea.isidori@uniroma1.it OBJECTIVES: Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. DATA SOURCE: A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. REVIEW METHODS: Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. RESULTS: Overall, 1,083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64.5 years (range 49.9--77.6) and mean serum testosterone was 10.9 nmol/l (range 7.8--19). Testosterone treatment produced: (i) a reduction of 1.6 kg (CI: 2.5--0.6) of total body fat, corresponding to -6.2% (CI: 9.2--3.3) variation of initial body fat, (ii) an increase in fat free mass of 1.6 kg (CI: 0.6--2.6), corresponding to +2.7% (CI: 1.1--4.4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size=0.3 standard mean difference (SMD), CI: -0.0 to 0.6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3.7% (CI: 1.0--6.4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = -0.6 SMD, CI: -1.0 to -0.2). Testosterone also reduced total cholesterol by 0.23 mmol/l (CI: -0.37 to -0.10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003). Sensitivity and meta-regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. CONCLUSION: The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems. PMID: 16117815 ------------- [5] Mol Neurobiol. 2015 Jul 8. [Epub ahead of print] Low Testosterone Level and Risk of Alzheimer's Disease in the Elderly Men: a Systematic Review and Meta-Analysis. Lv W(1), Du N(1), Liu Y(1), Fan X(1), Wang Y(1), Jia X(2), Hou X(3), Wang B(4). Sex steroids can positively affect the brain function, and low levels of sex steroids may be associated with worse cognitive function in the elderly men. However, previous studies reported contrary findings on the relationship between testosterone level and risk of Alzheimer's disease in the elderly men. The objective of this study was to comprehensively assess the relationship between low testosterone level and Alzheimer's disease risk in the elderly men using a meta-analysis. Only prospective cohort studies assessing the influence of low testosterone level on Alzheimer's disease risk in elderly men were considered eligible. Relative risks (RRs) with 95 % confidence intervals (95 % CI) were pooled to assess the risk of Alzheimer's disease in elderly men with low testosterone level. Seven prospective cohort studies with a total of 5251 elderly men and 240 cases of Alzheimer's disease were included into the meta-analysis. There was moderate degree of heterogeneity among those included studies (I (2) = 47.2 %). Meta-analysis using random effect model showed that low plasma testosterone level was significantly associated with an increased risk of Alzheimer's disease in elderly men (random RR = 1.48, 95 % CI 1.12-1.96, P = 0.006). Sensitivity analysis by omitting one study by turns showed that there was no obvious change in the pooled risk estimates, and all pooled RRs were statistically significant. This meta-analysis supports that low plasma testosterone level is significantly associated with increased risk of Alzheimer's disease in the elderly men. Low testosterone level is a risk factor of worse cognitive function in the elderly men. PMID: 26154489 ------------- [6] BMC Med. 2013 Apr 18;11:108. doi: 10.1186/1741-7015-11-108. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. Xu L(1), Freeman G, Cowling BJ, Schooling CM. Author information: (1)School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China. Comment in Evid Based Med. 2014 Feb;19(1):32-3. BACKGROUND: Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. METHODS: A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using "("testosterone" or "androgen") and trial and ("random*")" with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. RESULTS: Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). CONCLUSIONS: The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy. PMID: 23597181
  14. All, It looks like an apple a day helps keep the grim reaper away, at least in elderly women according to this new study [1] shared by Al Pater (thanks Al!). Researchers followed 1500 Australian women for 15 years, assessing their intake of various fruits every few years. Over the years their reported intake of apples and other fruits remained quite stable. The authors focused on the four fruits that made up the bulk (75%) of total fruit consumption - apples (20%), pears (11%), citrus fruit (23%), & bananas (21%). They found that women who ate more than 100g of apple per day (for reference, an average medium apple weighs 182g) had a 35% lower risk of all-cause mortality during the follow-up period, even after adjusting for a bunch of potential confounders, including age, BMI, smoking status, socio-economic status, diabetes, CVD, cancer, use of antihypertensive medication, use of cholesterol-lowering medication, use of low-dose aspirin, physical activity, energy intake and alcohol intake. Here are a couple interesting figures from the full text (available from Al). First, a needle plot of morality for the different fruits and causes of death: As you can see, pears and especially citrus weren't all that great for mortality. But apples, bananas and total fruit were all beneficial. Interestingly, bananas were the best of all these fruit for cardiovascular mortality, perhaps because of the important role potassium plays in CVD risk [2]. The one reservation/caveat I can see is that higher apple intake is associated with lots of other markers for an overall healthy diet, as you can see from this figure: Women who ate a lot of apples also ate (not surprisingly) a lot more fiber, flavonoids, total fruit etc. Although the authors didn't report on it, I suspect they also probably ate more vegetables, less trans and saturated fat, etc. So while apples are certainly healthy, they may also be an indicator of an overall healthy diet and lifestyle, and therefore not the (entire) cause of reduced mortality in these women. --Dean -------------- [1] Apple intake is inversely associated with all-cause and disease-specific mortality in elderly women. Hodgson JM, Prince RL, Woodman RJ, Bondonno CP, Ivey KL, Bondonno N, Rimm EB, Ward NC, Croft KD, Lewis JR. Br J Nutr. 2016 Mar;115(5):860-7. doi: 10.1017/S0007114515005231. Epub 2016 Jan 20. Abstract Higher fruit intake is associated with lower risk of all-cause and disease-specific mortality. However, data on individual fruits are limited, and the generalisability of these findings to the elderly remains uncertain. The objective of this study was to examine the association of apple intake with all-cause and disease-specific mortality over 15 years in a cohort of women aged over 70 years. Secondary analyses explored relationships of other fruits with mortality outcomes. Usual fruit intake was assessed in 1456 women using a FFQ. Incidence of all-cause and disease-specific mortality over 15 years was determined through the Western Australian Hospital Morbidity Data system. Cox regression was used to determine the hazard ratios (HR) for mortality. During 15 years of follow-up, 607 (41·7 %) women died from any cause. In the multivariable-adjusted analysis, the HR for all-cause mortality was 0·89 (95 % CI 0·81, 0·97) per sd (53 g/d) increase in apple intake, HR 0·80 (95 % CI 0·65, 0·98) for consumption of 5-100 g/d and HR 0·65 (95 % CI 0·48, 0·89) for consumption of >100 g/d (an apple a day), compared with apple intake of <5 g/d (P for trend=0·03). Our analysis also found that higher apple intake was associated with lower risk for cancer mortality, and that higher total fruit and banana intakes were associated lower risk of CVD mortality (P<0·05). Our results support the view that regular apple consumption may contribute to lower risk of mortality. Key words Apples; Fruits; All-cause mortality; Disease-specific mortality; CVD; Cancer PMID: 26787402 -------------- [2] J Clin Hypertens (Greenwich). 2002 May-Jun;4(3):198-206. Importance of potassium in cardiovascular disease. Sica DA(1), Struthers AD, Cushman WC, Wood M, Banas JS Jr, Epstein M. Author information: (1)Section of Clinical Pharmacology and Hypertension, Division of Nephrology, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA 23298, USA. dsica@hsc.vcu.edu The pivotal role of potassium (K+) in cardiovascular disease and the importance of preserving potassium balance have become clinical hot points, particularly as relates to new and emerging cardioprotective and renoprotective therapies that promote potassium retention. Although clinicians may be aware of the critical nature of this relationship, quite frequently there is some uncertainty as to the best way to monitor potassium levels in the face of a host of pathologic states and/or accompanying drug therapies that affect serum levels and/or total body potassium balance. Moreover, guidelines for monitoring of serum potassium levels are at best tentative and oftentimes are translated according to the level of concern of the respective physician. To address these uncertainties, an expert group was convened that included representatives from multiple disciplines. They attempted to reach consensus on the importance of K+ in hypertension, stroke, and arrhythmias as well as practical issues on maintaining K+ balance and avoiding K+ depletion. Because of the complexity of this topic, issues of hyperkalemia will be addressed in a forthcoming manuscript. Copyright 2002 Le Jacq Communications, Inc. PMID: 12045369
  15. All, I'm not a big proponent of eating fish, being a vegan myself. But in the interest of presenting the fact, here is a new meta-analysis [1] from Al (thanks Al!) that seems to show eating more fish is associated with reduced all-cause mortality. Specifically, among the almost 700,000 subjects across 12 prospective cohort studies, those who ate the most fish were 6% less likely to die during the follow-up period than those who ate the least fish (RR=0.94, 95% confidence interval (CI): 0.90, 0.98; I(2)=39.1%, P=0.06). Here from the full text is the forest plot of mortality risk across the 12 studies: As you can see, for most of the studies the confidence interval spans the centerline, and several are actually right of center (higher death risk for fish eating). Nevertheless, the center of mass is left of center - meaning reduced mortality risk when the studies are all combined together. Before you get too excited Saul and other fish-eating enthusiasts, consider the following.The authors did several additional sensitivity analyses to see how much the apparent benefits of eating fish depended on various factors. I think what they found was telling. Here is the table with the results, with a few items highlighted: What these sensitivity analyses show is that the mortality benefit of eating fish was attenuated to the point of being non-significant in: The six studies that were large (40,000+ subjects) The six studies that had long follow-up periods (12+ years) The four studies that compensated for differences in red meat intake between fish eaters and fish abstainers The eight studies that compensated for differences in fruit and veggie intake between fish eaters and fish abstainers Given the small (6%) benefit to start with, coupled with all these attenuating factors, it appears to me that the purported benefits of eating fish for all-cause mortality are probably marginal at best. --Dean ----------- [1] Eur J Clin Nutr. 2016 Feb;70(2):155-61. doi: 10.1038/ejcn.2015.72. Epub 2015 May 13. Fish consumption and all-cause mortality: a meta-analysis of cohort studies. Zhao LG, Sun JW, Yang Y, Ma X, Wang YY, Xiang YB. full text: http://www.nature.com.sci-hub.io/ejcn/journal/v70/n2/full/ejcn201572a.html Abstract12 BACKGROUND/OBJECTIVES: Although fish consumption may have an influence on specific mortality of major chronic diseases, the relationship between fish consumption and all-cause mortality remains inconsistent. SUBJECTS/METHODS: We performed a systematic search of publications using PubMed and Web of science up to 31 December 2014. Summary relative risk (RR) for the highest versus lowest category of fish consumption on risk of all-cause mortality was calculated by using a random effects model. Potential nonlinear relation was tested by modeling fish intake using restricted cubic splines with three knots at fixed percentiles of the distribution. RESULTS: Twelve prospective cohort studies with 672 389 participants and 57 641 deaths were included in this meta-analysis. Compared with the lowest category, the highest category of fish intake was associated with about a 6% significantly lower risk of all-cause mortality (RR=0.94, 95% confidence interval (CI): 0.90, 0.98; I(2)=39.1%, P=0.06). The dose-response analysis indicated a nonlinear relationship between fish consumption and all-cause mortality. Compared with never consumers, consumption of 60 g of fish per day was associated with a 12% reduction (RR=0.88, 95% CI: 0.83, 0.93) in risk of total death. CONCLUSIONS: These results imply that fish consumption was associated with a reduced risk of all-cause mortality. PMID: 25969396
  16. This new study in the Lancet [1] (popular account here) is sad news for us happy people. In the study, researchers polled 700,000 women in 1996-2001 about their level of happiness, and other health markers. Then the followed up in 2012 to see how many had died, and if there was a correlation between self-reported happiness and mortality that was independent of baseline health and other (socioeconomic) factors. From the full text, here is an interesting chart of what lifestyle and health parameters made these women the most happy or unhappy - i.e. factors that correlated with self-reported happiness. The most happiness-inducing was being married with children. The most unhappiness-inducing was sleeping less than 7h per night. If I'm reading it right, it also appears the more education the women had, the less happy they reported themselves to be. Anyway, what these researchers were interested was the relationship of happiness and health/longevity. First, they eliminated women who reported having "life threatening health disorders" (e.g. cancer, heart disease, etc.) at baseline, to avoid their (presumed) unhappiness from interfering with the analysis. In the disease-free women that remained, they found unhappy women were 30% more likely to die than those who reported being happy "most of the time" or "usually happy": In crude analyses adjusted only for age, unhappiness remained associated with increased mortality (RR 1·29, 95% CI 1·25–1·33) But they found that women who self-rated their health as fair or poor were 67% more likely to die during follow-up than those who rated it good or excellent. Once they adjusted for the correlation between self-rated health and happiness, the association between happiness and reduced mortality disappeared: ]O]nce we adjusted for self-rated health, unhappiness was no longer significantly associated with all-cause mortality (RR 1·02, 0·98–1·05; table). Here is the most relevant graph, showing just how flat the mortality rate (vertical axis) is across different levels of reported happiness (horizontal axis), but that people with poor self-reported health have a mortality curve shifted much higher than those reporting themselves to be in good or excellent health: In short, this study appears to suggest that self-rated poorer health, even among women free from life threatening health conditions, was a predictor of unhappiness at the time of the survey and increased subsequent mortality. But self-reported (un)happiness itself was not an independent predictor of mortality. Another measure of well-being the researchers surveyed, and found not to be independently associated with reduced subsequent mortality was whether the women reported feeling "in control, relaxed, or not stressed". So it looks like from this study being happy and stress-free makes one's life more pleasant, but not any longer. --Dean ---------- [1] The Lancet 09 December 2015 http://dx.doi.org/10.1016/S0140-6736(15)01087-9 Does happiness itself directly affect mortality? The prospective UK Million Women Study Bette Liu, Sarah Floud, Kirstin Pirie, Prof Jane Green, Prof Richard Peto, Prof Valerie Beral Free full text: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01087-9/fulltext Summary Background Poor health can cause unhappiness and poor health increases mortality. Previous reports of reduced mortality associated with happiness could be due to the increased mortality of people who are unhappy because of their poor health. Also, unhappiness might be associated with lifestyle factors that can affect mortality. We aimed to establish whether, after allowing for the poor health and lifestyle of people who are unhappy, any robust evidence remains that happiness or related subjective measures of wellbeing directly reduce mortality. Methods The Million Women Study is a prospective study of UK women recruited between 1996 and 2001 and followed electronically for cause-specific mortality. 3 years after recruitment, the baseline questionnaire for the present report asked women to self-rate their health, happiness, stress, feelings of control, and whether they felt relaxed. The main analyses were of mortality before Jan 1, 2012, from all causes, from ischaemic heart disease, and from cancer in women who did not have heart disease, stroke, chronic obstructive lung disease, or cancer at the time they answered this baseline questionnaire. We used Cox regression, adjusted for baseline self-rated health and lifestyle factors, to calculate mortality rate ratios (RRs) comparing mortality in women who reported being unhappy (ie, happy sometimes, rarely, or never) with those who reported being happy most of the time. Findings Of 719 671 women in the main analyses (median age 59 years [iQR 55–63]), 39% (282 619) reported being happy most of the time, 44% (315 874) usually happy, and 17% (121 178) unhappy. During 10 years (SD 2) follow-up, 4% (31 531) of participants died. Self-rated poor health at baseline was strongly associated with unhappiness. But after adjustment for self-rated health, treatment for hypertension, diabetes, asthma, arthritis, depression, or anxiety, and several sociodemographic and lifestyle factors (including smoking, deprivation, and body-mass index), unhappiness was not associated with mortality from all causes (adjusted RR for unhappy vs happy most of the time 0·98, 95% CI 0·94–1·01), from ischaemic heart disease (0·97, 0·87–1·10), or from cancer (0·98, 0·93–1·02). Findings were similarly null for related measures such as stress or lack of control. Interpretation In middle-aged women, poor health can cause unhappiness. After allowing for this association and adjusting for potential confounders, happiness and related measures of wellbeing do not appear to have any direct effect on mortality. PMID: 26684609
  17. All, As discussed in this thread, evidence suggests ALA may be beneficial for brain health in most people, while DHA/EPA may be a mixed blessing - only helpful for avoid Alzheimer's disease (but not other forms of dementia) in those with the APOE4 allele. And as discussed in this thread, fatty fish high in DHA/EPA may be detrimental for cardiovascular health if contaminated with PCBs, as was the case in several studies of Swedish fish eaters. But this new study [1] shared by Al Pater (thanks Al!) found in another population of fish eaters, this time from Spain, dietary DHA/EPA may in fact be beneficial for avoiding cardiovascular mortality. But dietary DHA/EPA was not significantly beneficial for all-cause mortality. For dietary Alpha Linolenic Acid (ALA) which is an omega-3 from plants (e.g. walnuts, olive oil, flax, chia seeds) the opposite was the case. Namely, dietary ALA reduced all-cause mortality, but not cardiovascular mortality risk. Putting the two together, people who met the dietary recommendations for both DHA/EPA and ALA had the lowest all-cause mortality risk - 37% lower than those who didn't meet either recommendation. Perhaps the fish from Spain have less PCBs than Swedish fish (no - I don't mean the candy :-) ). The full text of the study did not address DHA/EPA supplements - DHA/EPA intake was assessed solely from dietary sources. So it is not clear if a similar beneficial effect could be achieved through a combination of ALA from plant sources and DHA/EPA supplements as fish oil or algae oil, both of which are less likely to be contaminated with mercury or PCBs than the flesh of whole fish. --Dean ------ [1] J Am Heart Assoc. 2016 Jan 26;5(1). pii: e002543. doi: 10.1161/JAHA.115.002543. Dietary Alpha-Linolenic Acid, Marine Omega-3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study. Sala-Vila A, Guasch-Ferré M, Hu FB, et al. http://jaha.ahajournals.org/content/5/1/e002543.long http://jaha.ahajournals.org/content/5/1/e002543.full.pdf+html Abstract BACKGROUND: Epidemiological evidence suggests a cardioprotective role of Alpha-linolenic acid (ALA), a plant-derived Omega-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine Omega-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long-chain n-3 polyunsaturated fatty acids (=/>500 mg/day). METHODS AND RESULTS: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-cause mortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-cause mortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). CONCLUSIONS: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids. KEYWORDS: fatty acid; nutrition; sudden cardiac death PMID: 26813890
  18. Al posted a new study [1], that appears to me to support the theory I've been promulgating for a while that what's important for health and longevity is the quality of one's diet and lifestyle, rather than the quantity of calories one eats. The study followed over 90,000 postmenopausal women for about 13 years to see how the baseline quality of their diet (as quantified by 4 popular dietary quality metrics) impacted subsequent mortality. The dietary quality metrics were designed to gauge how well the women adhered to commonly-accepted 'good' dietary patterns, like following a Mediterranean Diet, or a DASH-like diet. All four shared much in common (emphasize fruits & vegetables, whole grains, avoid red & processed meat, etc.), and fortunately all four resulted in similar outcomes in this study, so I'll collapse all four in my brief discussion of the results below into a single notion of a "good diet". What they found was the women who had the best diet (i.e. were in the highest quintile of 'good diet' score relative to lowest quintile) had about a 20-25% lower risk of dying during the 13 year follow-up period. They also had a lower BMI (25-26 vs. 28-29) although weren't especially slim, and the exercised more than the women who ate the crappiest diet, although the researchers attempted to factor out BMI, exercise, and calories (see next point) from their statistical analysis to focus on the link between diet quality and mortality. On average the women who were eating the best diet and hence were healthier & longer-lived didn't report eating any fewer calories than the women eating the crappiest diet (although as we know food frequency questionnaires are fraught with difficulties...), they were just eating healthy foods rather than unhealthy ones. In short, this is yet one more study showing that dramatic improvements in health/longevity, on par with what we hope to achieve via CR, seem to be attainable by following a healthy obesity-avoiding diet & lifestyle, but without calorie restriction. --Dean -------- [1] Comparing indices of diet quality with chronic disease mortality risk in postmenopausal women in the Women's Health Initiative Observational Study: evidence to inform national dietary guidance. George SM, Ballard-Barbash R, Manson JE, Reedy J, Shikany JM, Subar AF, Tinker LF, Vitolins M, Neuhouser ML. Am J Epidemiol. 2014 Sep 15;180(6):616-25. doi: 10.1093/aje/kwu173. Epub 2014 Jul 17. PMID: 25035143 Free PMC Article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157698/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157698/pdf/kwu173.pdf Abstract Poor diet quality is thought to be a leading risk factor for years of life lost. We examined how scores on 4 commonly used diet quality indices-the Healthy Eating Index 2010 (HEI), the Alternative Healthy Eating Index 2010 (AHEI), the Alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH)-are related to the risks of death from all causes, cardiovascular disease (CVD), and cancer among postmenopausal women. Our prospective cohort study included 63,805 participants in the Women's Health Initiative Observational Study (from 1993-2010) who completed a food frequency questionnaire at enrollment. Cox proportional hazards models were fit using person-years as the underlying time metric. We estimated multivariate hazard ratios and 95% confidence intervals for death associated with increasing quintiles of diet quality index scores. During 12.9 years of follow-up, 5,692 deaths occurred, including 1,483 from CVD and 2,384 from cancer. Across indices and after adjustment for multiple covariates, having better diet quality (as assessed by HEI, AHEI, aMED, and DASH scores) was associated with statistically significant 18%-26% lower all-cause and CVD mortality risk. Higher HEI, aMED, and DASH (but not AHEI) scores were associated with a statistically significant 20%-23% lower risk of cancer death. These results suggest that postmenopausal women consuming a diet in line with a priori diet quality indices have a lower risk of death from chronic disease. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US. KEYWORDS: diet; diet quality indices; mortality risk; postmenopausal women; prospective cohort study
  19. [Note: This is my first thread on the new "General Health & Longevity" forum - thanks for making it!] Yet another study has found drinking a surprisingly large number of cups of coffee per day to be health promoting. This new study [1] in the Journal Circulation by Harvard researchers (press release, including a video, here) used epidemiological data from 74,890 women in the Nurses' Health Study, 93,054 women in the Nurses' Health Study 2, and 40,557 men in the Health Professionals Follow-up Study. Participants completed food questionnaires every four years during an average follow-up period of 22.5 years, providing researchers with coffee consumption data. There appeared to be a shallow, U-shaped mortality curve for coffee drinking, with the greatest reduction in non-smoker mortality (15%) among those who consumed 3-5 cups of coffee per day. Greater than 5 cups per day reduced all-cause mortality by slightly less (12%) when compared to never-drinkers. Both caffeinated and decaf coffee was found to reduce mortality. The causes of death that were significantly lower among coffee drinkers were cardiovascular disease, neurological diseases, and suicide. This Harvard study is in agreement with another large, epidemiological study [2] from earlier this year which found an even greater reduction in all-cause and cause-specific morality among a Japanese cohort of 90,000 people followed for 19 years. It too found a sweet spot around 3-4 cups per day, with a reduction in all-cause mortality of 24%. So once again, coffee is found to be good for you. But remember not to drink it too hot, and be sure to filter it, preferably with a paper filter. ---------- [1] Circulation November 16, 2015, Published online before print doi: 10.1161/CIRCULATIONAHA.115.017341 Association of Coffee Consumption with Total and Cause-Specific Mortality in Three Large Prospective Cohorts Ming Ding1; Ambika Satija1; Shilpa N. Bhupathiraju1; Yang Hu1; Qi Sun2; Jiali Han3; Esther Lopez-Garcia4; Walter Willett2; Rob M. van Dam5; Frank B. Hu2* Abstract Background—The association between consumption of caffeinated and decaffeinated coffee and risk of mortality remains inconclusive. Methods and Results—We examined the associations of consumption of total, caffeinated, and decaffeinated coffee with risk of subsequent total and cause-specific mortality among 74,890 women in the Nurses' Health Study (NHS), 93,054 women in the NHS 2, and 40,557 men in the Health Professionals Follow-up Study. Coffee consumption was assessed at baseline using a semi-quantitative food frequency questionnaire. During 4,690,072 person-years of follow-up, 19,524 women and 12,432 men died. Consumption of total, caffeinated, and decaffeinated coffee were non-linearly associated with mortality. Compared to non-drinkers, coffee consumption one to five cups/d was associated with lower risk of mortality, while coffee consumption more than five cups/d was not associated with risk of mortality. However, when restricting to never smokers, compared to non-drinkers, the HRs of mortality were 0.94 (0.89 to 0.99) for ≤ 1 cup/d, 0.92 (0.87 to 0.97) for 1.1-3 cups/d, 0.85 (0.79 to 0.92) for 3.1-5 cups/d, and 0.88 (0.78 to 0.99) for > 5 cups/d (p for non-linearity = 0.32; p for trend < 0.001). Significant inverse associations were observed for caffeinated (p for trend < 0.001) and decaffeinated coffee (p for trend = 0.022). Significant inverse associations were observed between coffee consumption and deaths due to cardiovascular disease, neurological diseases, and suicide. No significant association between coffee consumption and total cancer mortality was found. Conclusions—Higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was associated with lower risk of total mortality. PMID: 26572796 ------------ [2] Am J Clin Nutr. 2015 May;101(5):1029-37. doi: 10.3945/ajcn.114.104273. Epub 2015 Mar 11. Association of coffee intake with total and cause-specific mortality in a Japanese population: the Japan Public Health Center-based Prospective Study. Saito E(1), Inoue M(1), Sawada N(1), Shimazu T(1), Yamaji T(1), Iwasaki M(1), Sasazuki S(1), Noda M(1), Iso H(1), Tsugane S(1). BACKGROUND: Despite the rising consumption of coffee worldwide, few prospective cohort studies assessed the association of coffee intake with mortality including total and major causes of death. OBJECTIVE: We aimed to investigate the association between habitual coffee drinking and mortality from all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale, population-based cohort study in Japan. DESIGN: We studied 90,914 Japanese persons aged between 40 and 69 y without a history of cancer, cerebrovascular disease, or ischemic heart disease at the time of the baseline study. Subjects were followed up for an average of 18.7 y, during which 12,874 total deaths were reported. The association between coffee intake and risk of total and cause-specific mortality was assessed by using a Cox proportional hazards regression model with adjustment for potential confounders. RESULTS: We showed an inverse association between coffee intake and total mortality in both men and women. HRs (95% CIs) for total death in subjects who consumed coffee compared with those who never drank coffee were 0.91 (0.86-0.95) for <1 cup/d, 0.85 (0.81-0.90) for 1-2 cups/d, 0.76 (0.70-0.83) for 3-4 cups/d, and 0.85 (0.75-0.98) for >5 cups/d (P-trend < 0.001). Coffee was inversely associated with mortality from heart disease, cerebrovascular disease, and respiratory disease. CONCLUSION: With this prospective study, we suggest that the habitual intake of coffee is associated with lower risk of total mortality and 3 leading causes of death in Japan. © 2015 American Society for Nutrition. PMID: 25762807
  20. Diet & Colon Cancer Prevention While researching the Adventists diet study for prostate cancer prevention, Al Pater kindly pointed me to a similar study [1] of diet and colon cancer risk among the Adventists in the AHS-2 study by the same authors (thanks Al!). It followed 96,000 Adventists of both genders for an average follow-up time of 7.3 years to see which diets were associated with a reduced risk of colon cancer. As expected, all vegetarians combined were 22% less likely than omnivores to develop any form of colon cancer during the follow-up (HR 0.78: 95% CI, 0.64-0.95). Here is the breakdown of colon cancer risk by various types of vegetarian diets, again relative to omnivores: Vegans 0.84 (95% CI, 0.59-1.19); lacto-ovo vegetarians 0.82 (95% CI, 0.65-1.02); pescovegetarians, 0.57 (95% CI, 0.40-0.82) semivegetarians, 0.92 (95% CI, 0.62-1.37) For colon cancer, it appears to be the pesky pesco-vegetarians who have the lowest risk of colon cancer. But vegans win overall, at least among this healthy Adventist population relative to all cancers (not just prostate or colon cancer), according to [2]. From the abstract: ... vegan diets showed statistically significant protection for overall cancer incidence (HR, 0.84; 95% CI, 0.72-0.99) in both genders combined. Here is the diagram from [2] comparing the overall cancer risk for different forms of vegetarian diets, relative to omnivores: If we look at the male & female line (first highlight) or the male-only line (second highlight) in the fully adjusted model (including adjusting for BMI), it is only the vegan dietary pattern that reaches the level of 0.05 significance, and is P < 0.05 for the combined gender group. The other vegetarian subgroups failed to show a statistically significant lower overall risk of cancer relative to omnivores. Go ahead - call my Dr. Greger. But thems the data... --Dean ----------- [1] JAMA Intern Med. 2015 May;175(5):767-76. doi: 10.1001/jamainternmed.2015.59. Vegetarian dietary patterns and the risk of colorectal cancers. Orlich MJ(1), Singh PN(2), Sabaté J(1), Fan J(2), Sveen L(2), Bennett H(2), Knutsen SF(1), Beeson WL(2), Jaceldo-Siegl K(1), Butler TL(2), Herring RP(2), Fraser GE(1). IMPORTANCE: Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. OBJECTIVE: To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS: The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96,354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77,659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES: Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURES: The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. RESULTS: During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64-0.95) for all colorectal cancers, 0.81 (95% CI, 0.65-1.00) for colon cancer, and 0.71 (95% CI, 0.47-1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59-1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians, 0.57 (95% CI, 0.40-0.82); and in semivegetarians, 0.92 (95% CI, 0.62-1.37) compared with nonvegetarians. Effect estimates were similar for men and women and for black and nonblack individuals. CONCLUSIONS AND RELEVANCE: Vegetarian diets are associated with an overall lower incidence of colorectal cancers. Pescovegetarians in particular have a much lower risk compared with nonvegetarians. If such associations are causal, they may be important for primary prevention of colorectal cancers. PMCID: PMC4420687 PMID: 25751512 ------------ [2] Cancer Epidemiol Biomarkers Prev. 2013 Feb;22(2):286-94. doi: 10.1158/1055-9965.EPI-12-1060. Epub 2012 Nov 20. Vegetarian diets and the incidence of cancer in a low-risk population. Tantamango-Bartley Y(1), Jaceldo-Siegl K, Fan J, Fraser G. Author information: (1)Department of Epidemiology and Biostatistics, Loma Linda University, School of Public Health, Loma Linda, CA 92350, USA. ytantamango@hotmail.com BACKGROUND: Cancer is the second leading cause of death in the United States. Dietary factors account for at least 30% of all cancers in Western countries. As people do not consume individual foods but rather combinations of them, the assessment of dietary patterns may offer valuable information when determining associations between diet and cancer risk. METHODS: We examined the association between dietary patterns (non-vegetarians, lacto, pesco, vegan, and semi-vegetarian) and the overall cancer incidence among 69,120 participants of the Adventist Health Study-2. Cancer cases were identified by matching to cancer registries. Cox proportional hazard regression analysis was conducted to estimate hazard ratios, with "attained age" as the time variable. RESULTS: A total of 2,939 incident cancer cases were identified. The multivariate HR of overall cancer risk among vegetarians compared with non-vegetarians was statistically significant [hr, 0.92; 95% confidence interval (CI), 0.85-0.99] for both genders combined. Also, a statistically significant association was found between vegetarian diet and cancers of the gastrointestinal tract (HR, 0.76; 95% CI, 0.63-0.90). When analyzing the association of specific vegetarian dietary patterns, vegan diets showed statistically significant protection for overall cancer incidence (HR, 0.84; 95% CI, 0.72-0.99) in both genders combined and for female-specific cancers (HR, 0.66; 95% CI, 0.47-0.92). Lacto-ovo-vegetarians appeared to be associated with decreased risk of cancers of the gastrointestinal system (HR, 0.75; 95% CI, 0.60-0.92). CONCLUSION: Vegetarian diets seem to confer protection against cancer. IMPACT: Vegan diet seems to confer lower risk for overall and female-specific cancer than other dietary patterns. The lacto-ovo-vegetarian diets seem to confer protection from cancers of the gastrointestinal tract. PMCID: PMC3565018 PMID: 23169929
  21. [Another one for the "Non-CR Health forum"...] Recently there has been much hype in the popular press, including a Time Magazine story, with this provocative cover: that claim we've been wrong about saturated fat (like butter) all along. These stories have been based on meta-analyses like this one [1], that purport to find no association between saturated fat and chronic diseases, even cardiovascular disease. One of my favorite nutrition bloggers, PlantPositive, did a thorough debunking of the Time story and the people & studies it uses as sources. Among other faults of these previous meta-analyses outlined in PlantPositive's post, some of the biggest problems include: Over correction by factoring out serum cholesterol in the analysis - which is elevated by saturate fat intake and so shouldn't be controlled for. Failing to factor out the low cholesterol of saturated fat eaters who take statins to control their cholesterol. Failing to account for the health effects of what people choose to eat instead when they don't eat saturated fat-rich foods. As I recall (but an unable to verify due to the archives being down... ), we talked about all these studies and their shortcomings on the CR email list before. But now, we have something even better than critical analysis of flawed studies. We have a new prospective cohort study [2] of some of the best data available on diet, lifestyle and health from the Health Professionals and Nurses Health Studies. It appears to do a much better job, particularly with respect to the third confounder - food substitution effects. Here is popular press coverage of the new study. The Harvard researchers have followed these two cohorts of 42K men and 84K women for over 30 years, assessing their diet, lifestyle and health repeatedly during that time. This study looked at their fat consumption habits, and in particular changes in those habits over time and how those changes relate to coronary heart disease (CHD). In a nutshell, they found that: Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10). Here is a graphical depiction of these results: As you can see, trans fat is toxic relative to any other foods, including saturate fat - no surprise. More interestingly, it is about a wash to substitute saturated fat with refined carbohydrates when it comes to heart disease risk. But substituting any of the following for saturated fat results in significantly reduced CHD risk - MUFA, PUFA and whole grain carbohydrates. PUFAs appear particularly protective. Unfortunately the study did not address other healthy carbohydrate sources besides whole grains, like fruits, vegetables or legumes (which I willing to bet would do at least as well as whole grains at reducing CHD risk relative to saturated fat). They also didn't discriminate between the health effects of different types of saturated fats, some of which might not be as bad as others (i.e. those found in plants vs. animal sources). One concern is that when people clean up their diet by eliminating saturated fat, they might also undertake other health promoting lifestyle changes, making it appear that reducing saturated fat was beneficial when it actually was the other changes that made the difference. The authors addressed this potential problem by controlling for a host of other factors in their analysis, including: The multivariable model was adjusted for total energy intake, the energy contribution from protein, cholesterol intake, alcohol intake, smoking status, body mass index, physical activity, use of vitamins and aspirin, family history of myocardial infarction and diabetes, and presence of baseline hypercholesterolemia and hypertension. These results confirm what I think most people have believed all along - that saturated fat is detrimental to heart health, but probably no more so than what people will normally eat instead, crappy carbs. This explains those previous studies that found lower saturated fat intake was often not associated with lower risk of heart disease - people who ate less saturated fat were eating more refined carbs instead, and so weren't any better off. But when you replace saturated fat-rich foods with healthy fats or healthy carbs, you reduce your risk of heart disease dramatically. --Dean --------------- [1] BMJ. 2015 Aug 11;351:h3978. doi: 10.1136/bmj.h3978. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. de Souza RJ(1), Mente A(2), Maroleanu A(3), Cozma AI(4), Ha V(5), Kishibe T(6), Uleryk E(7), Budylowski P(8), Schünemann H(9), Beyene J(10), Anand SS(11). OBJECTIVE: To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled. Heterogeneity was assessed and quantified. Potential publication bias was assessed and subgroup analyses were undertaken. The GRADE approach was used to evaluate quality of evidence and certainty of conclusions. RESULTS: For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90 501-339 090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12 942-230 135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27). Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18 (1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73 to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated fat and all outcomes was "very low." The certainty of associations of trans fat with CHD outcomes was "moderate" and "very low" to "low" for other associations. CONCLUSIONS: Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats. © de Souza et al 2015. PMCID: PMC4532752 PMID: 26268692 ------------ [2] J Am Coll Cardiol. 2015 Oct 6;66(14):1538-48. doi: 10.1016/j.jacc.2015.07.055. Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study. Li Y(1), Hruby A(1), Bernstein AM(2), Ley SH(1), Wang DD(1), Chiuve SE(3), Sampson L(1), Rexrode KM(4), Rimm EB(5), Willett WC(5), Hu FB(6). BACKGROUND: The associations between dietary saturated fats and the risk of coronary heart disease (CHD) remain controversial, but few studies have compared saturated with unsaturated fats and sources of carbohydrates in relation to CHD risk. OBJECTIVES: This study sought to investigate associations of saturated fats compared with unsaturated fats and different sources of carbohydrates in relation to CHD risk. METHODS: We followed 84,628 women (Nurses' Health Study, 1980 to 2010), and 42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years. RESULTS: During 24 to 30 years of follow-up, we documented 7,667 incident cases of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates from whole grains were significantly associated with a lower risk of CHD comparing the highest with lowest quintile for PUFAs (hazard ratio : 0.80, 95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend = 0.003). In contrast, carbohydrates from refined starches/added sugars were positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p trend = 0.04). Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10). CONCLUSIONS: Our findings indicate that unsaturated fats, especially PUFAs, and/or high-quality carbohydrates can be used to replace saturated fats to reduce CHD risk. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. PMCID: PMC4593072 [Available on 2016-10-06] PMID: 26429077