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  2. Sedentary leisure-time in relation to mortality and survival time. Larsson SC, Wolk A. J Sci Med Sport. 2018 Nov 28. pii: S1440-2440(18)30282-2. doi: 10.1016/j.jsams.2018.11.020. [Epub ahead of print] PMID: 30522752 Abstract OBJECTIVE: To examine the association between sedentary leisure-time and all-cause mortality and differences in survival time. DESIGN: Prospective cohort study. METHODS: Information on sedentary leisure-time, defined as TV viewing and/or sitting reading, was collected from 72003 Swedish adults who were 45-83 (median 60) years of age and completed a self-administered questionnaire at baseline and were followed up for 17years through linkage with the Swedish Death Register. RESULTS: The association between sedentary leisure-time and all-cause mortality was modified by age with a more pronounced association in middle-aged (<60years of age) than in older adults (≥60years of age) (p-interaction<0.001). During follow-up, 3358 and 15217 deaths occurred in the middle-aged and older age group, respectively. The multivariable-adjusted hazard ratios for the highest (>6h/day) versus lowest category (<1h/day) of sedentary leisure-time were 1.72 (95% confidence interval [CI] 1.29-2.30) in middle-aged adults and 1.19 (95% CI 1.05-1.36) in older adults. This corresponded to a difference in survival time of respectively 2.4 (95% CI -4.1 to -0.8) years and 1.5 (95% CI -2.2 to -0.7) years. CONCLUSIONS: Prolonged sedentary leisure-time was associated with a significantly decreased survival time up to 2.4 years in middle-aged adults. KEYWORDS: Cohort studies; Mortality; Sedentary leisure-time; Survival; TV viewing Can the design of a running shoe help prevent injury? A B.C. researcher says he has the answer Barefoot? Big sole? For years, runners have been getting conflicting advice about the ideal shoe Kelly Crowe · CBC News · Posted: Dec 15, 2018 https://www.cbc.ca/news/health/running-shoe-injury-prevention-second-opinion-1.4947408 "One study reported that in a single year about 50 per cent of all runners will suffer knee injuries, or other running-related problems including plantar fasciitis, Achilles tendinopathy and stress fractures of the foot and the tibia." Growth Signaling and Longevity in Mouse Models. Kim SS, Lee CK. BMB Rep. 2018 Dec 14. pii: 4454. [Epub ahead of print] PMID: 30545442 Abstract Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns. Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: a systematic review and meta-analysis. Gjuladin-Hellon T, Davies IG, Penson P, Amiri Baghbadorani R. Nutr Rev. 2018 Dec 13. doi: 10.1093/nutrit/nuy049. [Epub ahead of print] PMID: 30544168 Abstract CONTEXT: Carbohydrate-restricted diets may increase low-density lipoprotein cholesterol and thereby cardiovascular risk. OBJECTIVE: A systematic review and meta-analyses were conducted to compare the effects of very low, low, and moderate carbohydrate, higher fat diets versus high-carbohydrate, low-fat diets on low-density lipoprotein cholesterol and other lipid markers in overweight/obese adults. DATA SOURCES: Medline, PubMed, Cochrane Central, and CINAHL Plus were searched to identify large randomized controlled trials (n > 100) with duration ≥ 6 months. DATA EXTRACTION: Eight randomized controlled trials (n = 1633; 818 carbohydrate-restricted diet, 815 low-fat diet) were included. DATA ANALYSIS: Quality assessment and risk of bias, a random effects model, and sensitivity and subgroup analyses based on the degree of carbohydrate restriction were performed using Cochrane Review Manager. Results were repor RESULTS: Carbohydrate-restricted diets showed no significant difference in low-density lipoprotein cholesterol after 6, 12, and 24 months. Although an overall pooled analysis statistically favored low-fat diets (0.07 mmol/L; 95% confidence interval [CI], 0.02-0.13; P = 0.009], this was clinically insignificant. High-density lipoprotein cholesterol and plasma triglycerides at 6 and 12 months favored carbohydrate-restricted diets (0.08 mmol/L; 95%CI, 0.06-0.11; P < 1 × 10-5 and -0.13 mmol/L; 95%CI, -0.19 to -0.08; P < 1 × 10-5, respectively). These favorable changes were more marked in the subgroup with very-low carbohydrate content (< 50 g/d; 0.12 mmol/L; 95%CI, 0.10-0.14; P < 1 × 10-5 and -0.19 mmol/L; 95%CI, -0.26 to -0.12; P = 0.02, respectively). CONCLUSIONS: Large randomized controlled trials of at least 6 months duration with carbohydrate restriction appear superior in improving lipid markers when compared with low-fat diets. Dietary guidelines should consider carbohydrate restriction as an alternative dietary strategy for the prevention/management of dyslipidemia for populations with cardiometabolic risk. Dietary intake of nutrients involved in folate-mediated one-carbon metabolism and risk for endometrial cancer. Lu J, Trabert B, Liao LM, Pfeiffer RM, Michels KA. Int J Epidemiol. 2018 Dec 13. doi: 10.1093/ije/dyy270. [Epub ahead of print] PMID: 30544261 Abstract BACKGROUND: Studies disagree as to whether intakes of folate-mediated one-carbon metabolism nutrients are associated with endometrial cancer. METHODS: Using data from the large, prospective NIH-AARP Diet and Health Study, we used Cox proportional hazards models to evaluate endometrial cancer risk associated with calorie-adjusted dietary intake of several B vitamins and methionine. All models accounted for age, race, body mass index (BMI), smoking, oral-contraceptive use, menopausal hormone therapy use and caloric intake. We estimated associations by time from baseline (≤3 or >3 years) and stratified models by BMI (<25 or ≥25 kg/m2). During 16 years of follow-up, we identified 2329 endometrial cancer cases among 114 414 participants. RESULTS: After adjustment for confounding, we observed increased risk for endometrial cancer with greater consumption of dietary total folate, natural folate, B2, B6 and B12 [hazard ratios (HRs) ranging from 1.14 to 1.24 for the highest quintile (Q5) vs the lowest (Q1)]. Higher intakes of total folate, natural folate, B6 and B12 continued to be associated with increased risk when limiting follow-up to >3 years from baseline. We observed risks for the highest intakes of B2 [Q5 vs Q1: HR 1.27 95% confidence interval (CI) 1.07-1.50], B12 (Q5 vs Q1: HR 1.38 CI 1.17-1.63) and methionine (Q5 vs Q1: HR 1.26 CI 1.07-1.48) among women who were overweight/obese, but not among normal/underweight women. CONCLUSIONS: Our findings indicate that one-carbon metabolism plays a role in endometrial carcinogenesis and exploration of this role in tissue and cellular biology studies is warranted. Dietary Fat Intake and Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Studies. Kim M, Park K. Nutrients. 2018 Dec 12;10(12). pii: E1963. doi: 10.3390/nu10121963. Review. PMID: 30545042 Abstract Dietary fat intake is associated with the risk of colorectal cancer (CRC); however, the results of epidemiological studies on this are controversial. Therefore, this study aimed to summarize the available scientific evidence regarding the association between dietary fat and the risk of CRC. We conducted a systematic search of PubMed, Web of Science, and the Cochrane library for articles related to dietary fat and the risk of CRC. The summary relative risks with 95% confidence intervals (CI) were calculated via a random effect model. Begg's test was used to detect publication bias. A total of 18 articles were identified. The pooled relative risk with 95% CI for the risk of CRC were 1.00 (95% CI: 0.90⁻1.12), 0.97 (95% CI: 0.86⁻1.10), 1.08 (95% CI: 0.92⁻1.26), and 0.99 (95% CI: 0.93⁻1.04) for total fat, saturated fatty acid, monounsaturated fatty acid, and polyunsaturated fatty acid, respectively. No significant associations were found in subgroup analyses. Begg's test for all exposures revealed no publication bias (total fat, p = 0.3; saturated fatty acid, p = 0.1; monounsaturated fatty acid, p = 0.08; polyunsaturated fatty acid, p = 0.2). The studies included in this review and meta-analysis revealed that dietary fats and fatty acids had no effects on the risk of CRC. KEYWORDS: colorectal neoplasms; dietary fats; fatty acids; meta-analysis; systematic review Calcium intake and survival after colorectal cancer diagnosis. Yang W, Ma Y, Smith-Warner SA, Song M, Wu K, Wang M, Chan AT, Ogino S, Fuchs CS, Poylin V, Ng K, Meyerhardt JA, Giovannucci EL, Zhang X. Clin Cancer Res. 2018 Dec 13. pii: clincanres.2965.2018. doi: 10.1158/1078-0432.CCR-18-2965. [Epub ahead of print] PMID: 30545821 Abstract PURPOSE: Although evidence suggests an inverse association between calcium intake and colorectal cancer incidence, the influence of calcium on survival after colorectal cancer diagnosis remains unclear. EXPERIMENTAL DESIGN: We prospectively assessed the association of postdiagnostic calcium intake with colorectal cancer-specific and overall mortality among 1,660 non-metastatic colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis and were followed up for death. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards regression. RESULTS: Comparing the highest to the lowest quartile intake of postdiagnostic total calcium, the multivariable HRs were 0.56 (95% CI, 0.32 to 0.96, P trend = 0.04) for colorectal cancer-specific mortality and 0.80 (95% CI, 0.59 to 1.09, P trend = 0.11) for all-cause mortality. Postdiagnostic supplemental calcium intake was also inversely associated with CRC-specific mortality (HR = 0.67; 95% CI, 0.42 to 1.06; P trend = 0.047) and all-cause mortality (HR = 0.71; 95% CI, 0.54 to 0.94; P trend = 0.008), although these inverse associations were primarily observed in women. In addition, calcium from diet or dairy sources was associated with lower risk in men. CONCLUSIONS: Higher calcium intake after the diagnosis may be associated with a lower risk of death among patients with colorectal cancer. If confirmed, these findings may provide support for the nutritional recommendations of maintaining sufficient calcium intake among colorectal cancer.
  3. AlPater

    Al's CR updates

    Modulation of senoinflammation by calorie restriction based on biochemical and Omics big data analysis. Bang E, Lee B, Noh SG, Kim DH, Jung HJ, Ha S, Yu BP, Chung HY. BMB Rep. 2018 Dec 14. pii: 4456. [Epub ahead of print] PMID: 30545444 Abstract Aging is a complex and progressive process characterized by physiological and functional decline with time that increases susceptibility to diseases. Aged-related functional change is accompanied by a low-grade, unresolved chronic inflammation as a major underlying mechanism. In order to explain aging in the context of chronic inflammation, a new integrative concept on age-related chronic inflammation is necessary that encompasses much broader and wider characteristics of cells, tissues, organs, systems, and interactions between immune and non-immune cells, metabolic and non-metabolic organs. We have previously proposed a novel concept of senescent (seno)-inflammation and provided its frameworks. This review summarizes senoinflammation concept and additionally elaborates modulation of senoinflammation by calorie restriction (CR). Based on aging and CR studies and systems-biological analysis of Omics big data, we observed that senescence associated secretory phenotype (SASP) primarily composed of cytokines and chemokines was notably upregulated during aging whereas CR suppressed them. This result further strengthens the novel concept of senoinflammation in aging process. Collectively, such evidence of senoinflammation and modulatory role of CR provide insights into aging mechanism and potential interventions, thereby promoting healthy longevity.
  4. Peter Attia interview with Navdep Chandler, a specialist in metabolism who underlines the role of ROS (reactive oxygen species) in cellular signalling. bottom line is that too many antioxydants (usually by supplements) can have a detrimental effect by inhibiting ROS signalling. the interview also contains an extensive discussion on metformin and longevity
  5. mccoy

    Back to CE but...

    At last we had a little snow, just around freezing point, absolutely nothing like siberia or Canada but I enjoyed walking outside in a sleevless polo shirt. Mostly I walked under a patio and only shortly under the snow. I find that, once full thermogenesis kicks into, cold is not perceived very much, unless it's windy. In more extreme temperatures it's probably better to don long sleeved shirts, unless your name is Wim Hof.
  6. This is a pretty interesting episode of the stemtalk series, with John Ioannidis, the professor who led the critical analysis on the PREDIMED study which turned out not to be a randomized study (although the results hold the same after a reassessment). https://www.ihmc.us/stemtalk/episode-77/ Ioannidis talks about some more or less surprising aspects of the world of medical literature. Nutritional epidemiology is criticized because of food questionnaires of uncertain value and the presence of many correlated variables (confounders). Signal to noise ratio is pretty low. Discussion on the difficulties of an objective assessment of the 'best' diet. More on the drawbacks of scientifical medical literature, like vested interests, repetition, favouring quantity over quality and so on. I wonder if there is some quick index to assess the quality of a paper without havign to consult specialists in the field.
  7. mccoy

    Coratina EVOO

    Oilalà sent me the lab report but it's relative to last year's crop, apparently the complete analyses are provided on january. TP as Tyrosol is 744 ppms and they expect it to be even higher this year, I don't know how they know that. Most probably the method is the colorimetric one cited by Michael, altough to be sure we should look at the relevant regulations cited in the certificate. Acidity is very low and the price is reasonable, although pretty high relative to local producers (12 euro per liter). I'm going to order 10 or 20 liters.
  8. Michael R

    Olive oil? Healthy or not?!

    All: in a post in another thread, I noted: Certainly, both the epidemiological evidence within Mediterranean countries where olive oil is used in meaningful quantities, as well as now large-scale clinical trials, demonstrate that plant-based MUFA, and especially real extra-virgin olive oil (or, though less celebrated, canola) reduces cardiovascular events and mortality, likely total mortality, and mortality from some cancers. A recent report supports this specifically for CVD risk, without even narrowly specifying olive oil (let alone high-phenolic EVOO):
  9. Tennis tops list of sports for increasing life expectancy Social connection might be the key to sport's longevity benefits Australian Broadcasting Corporation · Posted: Dec 10, 2018 https://www.cbc.ca/news/health/sports-life-expectancy-1.4939918 Sarcopenia Definitions and Their Associations With Mortality in Older Australian Women. Sim M, Prince RL, Scott D, Daly RM, Duque G, Inderjeeth CA, Zhu K, Woodman RJ, Hodgson JM, Lewis JR. J Am Med Dir Assoc. 2018 Dec 5. pii: S1525-8610(18)30590-5. doi: 10.1016/j.jamda.2018.10.016. [Epub ahead of print] PMID: 30527277 Abstract OBJECTIVES: To investigate the relationship of 4 sarcopenia definitions with long-term all-cause mortality risk in older Australian women. DESIGN: Data from the Perth Longitudinal Study in Aging Women from 2003 to 2013 was examined in this prospective cohort study. The 4 sarcopenia definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and adapted FNIH (AUS-POPF) and EWGSOP (AUS-POPE) definitions using Australian population-specific cut-points [<2 standard deviation (SD)] below the mean of young healthy Australian women. All-cause mortality was captured via linked data systems. SETTING AND PARTICIPANTS: In total, 903 community-dwelling older Australian women (baseline mean age 79.9 ± 2.6 years) with concurrent measures of muscle strength (grip strength), physical function (timed-up-and-go; TUG) and appendicular lean mass (ALM) were included. MEASURES: Cox-proportional hazards modeling was used to examine the relationship between sarcopenia definitions and mortality over 5 and 9.5 years. RESULTS: Baseline prevalence of sarcopenia by the 4 definitions differed substantially [FNIH (9.4%), EWGSOP (24.1%), AUS-POPF (12.0%), AUS-POPE (10.7%)]. EWGSOP and AUS-POPE had increased age-adjusted hazard ratios (aHRs) for mortality over 5 years [aHR 1.88 95% confidence interval (CI) (1.24‒2.85), P < .01; aHR 2.52 95% CI (1.55‒4.09), P < .01, respectively] and 9.5 years (aHR 1.39 95% CI (1.06‒1.81), P = .02; aHR 1.94 95% CI (1.40‒2.69), P < .01, respectively). No such associations were observed for FNIH or AUS-POPF. Sarcopenia components including weaker grip strength (per SD, 4.9 kg; 17%) and slower TUG (per SD, 3.1 seconds; 40%) but not ALM adjusted-variants (ALM/body mass index or ALM/height2) were associated with greater relative hazards for mortality over 9.5 years. CONCLUSIONS/RELEVANCE: Unlike FNIH, the EWGSOP sarcopenia definition incorporating weak muscle strength and/or poor physical function was related to prognosis, as was the regionally adapted version of EWGSOP. Although sarcopenia definitions were not developed based on prognosis, this is an important consideration for globally standardizing the sarcopenia framework. KEYWORDS: Mortality; geriatrics; lean mass; muscle strength; physical function The tooth loss and mortality from all causes, cardiovascular diseases and coronary heart disease: Systematic review and dose-response meta-analysis. Peng J, Song JK, Han J, Chen Z, Yin X, Zhu J, Song J. Biosci Rep. 2018 Dec 7. pii: BSR20181773. doi: 10.1042/BSR20181773. [Epub ahead of print] PMID: 30530864 http://www.bioscirep.org/content/ppbioscirep/early/2018/12/07/BSR20181773.full.pdf Abstract BACKGROUND: The association of tooth loss with mortality from all causes, cardiovascular diseases (CVD), and coronary heart disease (CHD) has been studied for many years; however, the results are inconsistent. METHOD: PubMed, Embase, Web of Knowledge, and Cochrane Oral Health Group's Trials Register databases were searched for papers published from 1966 to August 2018. We conducted dose-response meta-analysis to quantitatively evaluate the relation between tooth loss and risk of mortality from all causes, CVD, and CHD. RESULTS: In this study, 18 prospective studies were considered eligible for analysis. In the analysis of linear association, the summarized relative risk (RR) values for each 10-, 20-, and 32-tooth loss for all-cause mortality were 1.15 (1.11-1.19), 1.33 (1.23-1.29), and 1.57 (1.39-1.51), respectively. Subgroup and sensitivity analyses showed consistent results. Subgroup and sensitivity analyses revealed inconsistent results. Tooth loss showed linear association with CHD mortality but not with CVD mortality. The susceptibility to all-cause mortality increased by almost 1.48 and 1.70 times for CVD and CHD, respectively, at very high tooth loss (28-32). The curve exhibited slight flattening; however, no statistical significance was detected. CONCLUSION: In the meta-analysis, our findings confirmed the positive relationship between tooth loss and susceptibility to all-cause mortality, but not for circulatory mortality. Tooth loss may be a potential risk marker for all-cause mortality: however, their association must be further validated through large prospective studies. KEYWORDS: CardioVascular Diseases; Coronary Heart Disease; Mortality; Systematic Review; Tooth Loss >>>>>>>>>>>>>>>> Gerodontology. 2005 Dec;22(4):234-7. Eight-year mortality associated with dental occlusion and denture use in community-dwelling elderly persons. Yoshida M1, Morikawa H, Yoshikawa M, Tsuga K, Akagawa Y. PMID: 16329232 Abstract OBJECTIVE: To evaluate the influence of dental occlusion, with or without the use of dentures, on mortality in community-dwelling elderly persons. SUBJECTS: A total of 1030 randomly selected healthy independent elderly aged 65 and over were surveyed in 1995. For the study reported here, subjects were classified into three groups according to the presence or absence of maxillo-mandibular tooth contacts. Subjects with no maxillo-mandibular tooth contacts were further subdivided into those with and without dentures. METHODS: Data on mortality were obtained from Kure City Council in September 2003. Cox regression models were used in analysing the risk for death with gender and age as covariates. RESULTS: Individuals whose teeth had contact in at least the bilateral premolar regions at baseline had 0.78 times (95% CI: 0.60-0.99) smaller risk for death during the succeeding 8 years than those who had no occlusion. Among those who had no occlusion with their own teeth, the risk for mortality among denture non-users was 1.52 times (95% CI: 1.25-1.83) higher than the risk for denture users. CONCLUSION: These results may support the view that, in the elderly; poor dental occlusion is associated with an increased risk for mortality and that, in the edentulous, the use of dentures is associated with a decreased risk for mortality. Erythrocyte sedimentation rate as an independent prognostic marker for mortality: a prospective population-based cohort study. Fest J, Ruiter R, Mooijaart SP, Ikram MA, van Eijck CHJ, Stricker BH. J Intern Med. 2018 Dec 9. doi: 10.1111/joim.12853. [Epub ahead of print] PMID: 30537394 https://sci-hub.tw/10.1111/joim.12853 Abstract BACKGROUND: A very high erythrocyte sedimentation rate (ESR) is usually an indication of underlying pathology. Additionally, a moderately elevated ESR may also be attributable to biological ageing. Whether the ESR is a prognostic factor for mortality, regardless of age, has been scarcely investigated. Therefore, the objective was to analyse the association between elevated ESR levels and the risk of mortality in a prospective cohort of the general population. METHODS: We studied data from the Rotterdam Study (1990-2014). ESR levels were measured at baseline and individuals were followed until death or end of study. Associations between moderately (20-50 mm h-1 ) and markedly (>50 mm h-1 ) elevated ESR levels and all-cause mortality were assessed using multivariate Cox proportional hazard models. RESULTS: In total, 5226 participants were included, and the mean age was 70.3 years. During a median follow-up time of 14.9 years, 3749 participants died (71.7%). After adjustment, both a moderately elevated ESR and a markedly elevated ESR were associated with a significantly higher risk of overall mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12-1.35 and HR 1.89, 95% CI 1.38-2.60, respectively]. Although the ESR becomes higher with age, in a group aged above 75 years, without any comorbidities, an ESR > 20 mm h-1 remained associated with a significantly increased risk of mortality (HR 1.29, 95%CI 1.01-1.64). CONCLUSION: An elevated ESR is an independent prognostic factor for mortality. Despite the fact that ESR increases with age, it remains associated with an increased risk of mortality and warrants close follow-up. KEYWORDS: ageing; erythrocyte sedimentation rate; general population; low-grade inflammation; mortality Social determinants, health status and 10-year mortality among 10,906 older adults from the English longitudinal study of aging: the ATHLOS project. Kollia N, Caballero FF, Sánchez-Niubó A, Tyrovolas S, Ayuso-Mateos JL, Haro JM, Chatterji S, Panagiotakos DB. BMC Public Health. 2018 Dec 10;18(1):1357. doi: 10.1186/s12889-018-6288-6. PMID: 30526556 https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-018-6288-6 https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-018-6288-6 Abstract BACKGROUND: In either rich or poor countries, people's health widely depends on the social conditions in which they live and work - the social determinants of health. The aim of the present work was to explore the association of educational and financial status with healthy aging and mortality. METHODS: Data from the English Longitudinal Study of Aging (ELSA) were studied (n = 10,906 participants, 64 ± 11 years, 55% women). A set of 45 self-reported health items and measured tests were used to generate a latent health metric reflecting levels of functioning referred to as health metric (higher values indicated better health status). Overall mortality after 10-years of follow-up (2002-2012) was recorded. RESULTS: Both education and household wealth over time were positively associated with the health metric (p < 0.001) and negatively with overall mortality (p < 0.001). Lifestyle behaviors (i.e., physical activity, smoking habits and alcohol consumption) mediated the effect of education and household wealth on the health metric and the latter mediated their effect on overall mortality. CONCLUSIONS: In conclusion, reducing socioeconomic disparities in health by improving the access to education and by providing financial opportunities should be among the priorities in improving the health of older adults. KEYWORDS: Education; Financial status; Health; Healthy aging; Mortality; Social determinants; Socioeconomic A 5-day high-fat diet rich in cottonseed oil improves cholesterol profiles and triglycerides compared to olive oil in healthy men. Polley KR, Oswell NJ, Pegg RB, Paton CM, Cooper JA. Nutr Res. 2018 Dec;60:43-53. doi: 10.1016/j.nutres.2018.09.001. Epub 2018 Sep 9. PMID: 30527259 https://sci-hub.tw/10.1016/j.nutres.2018.09.001 Abstract Modifying dietary fat composition is important for minimizing cardiovascular disease risk. The purpose of this study was to determine the effects of a 5-day, high-fat diet rich in cottonseed oil (CSO) or olive oil (OO) on lipid profiles. Based on previous human and animal models, we hypothesized that the CSO-rich diet would lead to lower fasting and postprandial lipid levels, whereas the OO-rich diet would not significantly change lipid levels in 5 days. Fifteen normal-weight men completed a randomized crossover design with 2 controlled feeding trials (3-day lead-in diet, prediet visit, 5-day CSO- or OO-rich diet, postdiet visit). The 5-day diets (50% fat) were rich in either CSO or OO. At pre- and postdiet visits, subjects consumed test meals rich in the oil that coincided with their 5-day diet, and blood draws were performed. Fasting total cholesterol, low-density lipoprotein cholesterol, and triglycerides (TG) were lower following CSO diet intervention (total cholesterol: 148.40 ± 6.39 to 135.93 ± 6.31 mg/dL; low-density lipoprotein cholesterol: 92.20 ± 5.57 to 78.13 ± 5.60 mg/dL; TG: 80.11 ± 4.91 to 56.37 ± 5.46 mg/dL for pre- to postdiet, respectively; P < .05). High-density lipoprotein cholesterol increased following CSO diet intervention (46.67 ± 2.41 to 50.24 ± 2.20 mg/dL for pre- to postdiet, respectively; P < .05). Postprandial TGs were lower following CSO diet (area under the curve of 954.28 ± 56.90 vs 722.16 ± 56.15 mg/dL/8 h for pre- vs postdiet, respectively; P < .01). No changes in blood lipids were found following OO diet. A 5-day CSO-rich diet led to improvements in cholesterol and TGs, whereas no changes were observed with an OO-rich diet. KEYWORDS: Cholesterol; Cottonseed oil; Lipids; Monounsaturated fat; Olive oil; Polyunsaturated fat; Postprandial Dietary changes and cognition over 2 years within a multidomain intervention trial-The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Lehtisalo J, Levälahti E, Lindström J, Hänninen T, Paajanen T, Peltonen M, Antikainen R, Laatikainen T, Strandberg T, Soininen H, Tuomilehto J, Kivipelto M, Ngandu T. Alzheimers Dement. 2018 Nov 23. pii: S1552-5260(18)33560-X. doi: 10.1016/j.jalz.2018.10.001. [Epub ahead of print] PMID: 30527596 https://www.alzheimersanddementia.com/article/S1552-5260(18)33560-X/pdf Abstract INTRODUCTION: Association between healthy diet and better cognition is well established, but evidence is limited to evaluate the effect of dietary changes adopted in older age. METHODS: We investigated the role of dietary changes in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) with 1260 at-risk participants (60-77 years) who were randomized to intensive multidomain intervention (including dietary counseling) or regular health advice for 2 years. Parallel process latent growth curves of adherence to dietary recommendations and cognitive performance were analyzed. RESULTS: Adherence to healthy diet at baseline predicted improvement in global cognition, regardless of intervention allocation (P = .003). Dietary improvement was associated with beneficial changes in executive function, especially in the intervention group (P = .008; P = .051 for groups combined). DISCUSSION: Dietary changes initiated during the intervention were related to changes in executive function in 2 years. Long-term diet appeared more influential for global cognition. KEYWORDS: Cognitive performance; Diet; Growth curve analysis; Older adults; Prevention Sleep duration and risk of end-stage renal disease: the Singapore Chinese Health Study. Geng TT, Jafar TH, Yuan JM, Koh WP. Sleep Med. 2018 Oct 24;54:22-27. doi: 10.1016/j.sleep.2018.10.007. [Epub ahead of print] PMID: 30529773 Abstract OBJECTIVES: Although epidemiological evidence suggests that short sleep duration may affect renal function, the influence of long sleep and risk of end-stage renal disease (ESRD) is unclear. We examined the association between sleep duration and risk of ESRD. METHODS: We investigated sleep duration and ESRD risk in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese in Singapore, who were aged 45-74 years at recruitment (1993-1998). Information on daily sleep duration (including naps), diet, medical history and other lifestyle factors was collected at recruitment from in-person interviews. ESRD cases were identified via linkage with the nationwide Singapore Renal Registry through year 2014. We used the Cox proportional hazards regression method to estimate hazard ratio (HR) and 95% confidence interval (CI) of ESRD in relation to sleep duration. RESULTS: After an average 16.8 years of follow-up, 1143 (1.81%) ESRD cases were documented. Sleep duration had a U-shaped association with risk of ESRD (P for quadratic trend < 0.001). Compared with participants with 7 h/day of sleep, the multivariable adjusted HR (95% CI) of ESRD was 1.43 (1.18-1.74) for short sleep (≤5 h/day) and 1.28 (1.03-1.60) for long sleep duration (≥9 h/day). The increased risk was stronger in participants with more than 10 years of follow-up compared to those with shorter follow-up time, especially for long sleep (P for interaction = 0.003). CONCLUSIONS: Our findings demonstrated that both short and long sleep durations were associated with a higher risk of ESRD in this Asian population. Plasma concentration of trimethylamine-N-oxide and risk of gestational diabetes mellitus. Li P, Zhong C, Li S, Sun T, Huang H, Chen X, Zhu Y, Hu X, Peng X, Zhang X, Bao W, Shan Z, Cheng J, Hu FB, Yang N, Liu L. Am J Clin Nutr. 2018 Sep 1;108(3):603-610. doi: 10.1093/ajcn/nqy116. PMID: 30535087 Abstract BACKGROUND: The microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been reported as a novel and independent risk factor for the development of cardiovascular and metabolic diseases, but the association with gestational diabetes mellitus (GDM) remains unclear. OBJECTIVE: The aim of this study was to investigate the association between plasma TMAO concentration and GDM in a 2-phase study. DESIGN: A 2-phase design was used in the current study. An initial phase included 866 participants (433 GDM cases and 433 matched controls) with fasting blood samples collected at the time of GDM screening (24-32 wk of gestation). An independent-phase study, with 276 GDM cases and 552 matched controls who provided fasting blood samples before 20 wk of gestation and who had GDM screened during 24-32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted in Wuhan, China, and the incidence of GDM in the cohort study was 10.8%. Plasma TMAO concentrations were determined by stable isotope dilution liquid chromatography-tandem mass spectrometry. GDM was diagnosed according to the American Diabetes Association criteria by using an oral-glucose-tolerance test. RESULTS: In the initial case-control study, the adjusted OR of GDM comparing the highest TMAO quartile with the lowest quartile was 1.94 (95% CI: 1.28, 2.93). Each SD increment of ln-transformed plasma TMAO was associated with 22% (95% CI: 5%, 41%) higher odds of GDM. In the nested case-control study, women in the highest quartile also had increased odds of GDM (adjusted OR: 2.06; 95% CI: 1.28, 3.31) compared with women in the lowest quartile, and the adjusted OR for GDM per SD increment of ln-transformed plasma TMAO was 1.26 (95% CI: 1.08, 1.47). CONCLUSIONS: Consistent findings from this 2-phase study indicate a positive association between plasma TMAO concentrations and GDM. Future studies are warranted to elucidate the underlying mechanisms. Food groups and intermediate disease markers: a systematic review and network meta-analysis of randomized trials. Schwingshackl L, Hoffmann G, Iqbal K, Schwedhelm C, Boeing H. Am J Clin Nutr. 2018 Sep 1;108(3):576-586. doi: 10.1093/ajcn/nqy151. PMID: 30535089 Abstract BACKGROUND: In previous meta-analyses of prospective observational studies, we investigated the association between food groups and risk of chronic disease. OBJECTIVE: The aim of the present network meta-analysis (NMA) was to assess the effects of these food groups on intermediate-disease markers across randomized intervention trials. DESIGN: Literature searches were performed until January 2018. The following inclusion criteria were defined a priori: 1) randomized trial (≥4 wk duration) comparing ≥2 of the following food groups: refined grains, whole grains, nuts, legumes, fruits and vegetables, eggs, dairy, fish, red meat, and sugar-sweetened beverages (SSBs); 2) LDL cholesterol and triacylglycerol (TG) were defined as primary outcomes; total cholesterol, HDL cholesterol, fasting glucose, glycated hemoglobin, homeostasis model assessment insulin resistance, systolic and diastolic blood pressure, and C-reactive protein were defined as secondary outcomes. For each outcome, a random NMA was performed, and for the ranking, the surface under the cumulative ranking curves (SUCRA) was determined. RESULTS: A total of 66 randomized trials (86 reports) comparing 10 food groups and enrolling 3595 participants was identified. Nuts were ranked as the best food group at reducing LDL cholesterol (SUCRA: 93%), followed by legumes (85%) and whole grains (70%). For reducing TG, fish (97%) was ranked best, followed by nuts (78%) and red meat (72%). However, these findings are limited by the low quality of the evidence. When combining all 10 outcomes, the highest SUCRA values were found for nuts (66%), legumes (62%), and whole grains (62%), whereas SSBs performed worst (29%). CONCLUSION: The present NMA provides evidence that increased intake of nuts, legumes, and whole grains is more effective at improving metabolic health than other food groups. For the credibility of diet-disease relations, high-quality randomized trials focusing on well-established intermediate-disease markers could play an important role. Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial. Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX, Gómez-Díaz RA, Almeda-Valdes P. Am J Clin Nutr. 2018 Sep 1;108(3):485-491. doi: 10.1093/ajcn/nqy152. PMID: 30535090 Abstract BACKGROUND: Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. OBJECTIVE: The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. DESIGN: We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group). METHODS: The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period. RESULTS: Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of -17.7% (-29.3% to -1.0%) in comparison to -2.8% (-30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350-1040 mU · L-1· min) to 671 mU · L-1· min (376-1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence. CONCLUSIONS: Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Wang Z, Bergeron N, Levison BS, Li XS, Chiu S, Jia X, Koeth RA, Li L, Wu Y, Tang WHW, Krauss RM, Hazen SL. Eur Heart J. 2018 Dec 10. doi: 10.1093/eurheartj/ehy799. [Epub ahead of print] PMID: 30535398 Abstract AIMS: Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metabolism and renal excretion. METHODS AND RESULTS: Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metabolism. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05). Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat failed to impact TMAO or its metabolites. CONCLUSION: Chronic dietary red meat increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks. Rice intake and risk of type 2 diabetes: the Singapore Chinese Health Study. Seah JYH, Koh WP, Yuan JM, van Dam RM. Eur J Nutr. 2018 Dec 10. doi: 10.1007/s00394-018-1879-7. [Epub ahead of print] PMID: 30535795 Abstract PURPOSE: The prevalence of type 2 diabetes (T2D) is increasing in Asian populations. White rice is a common staple food in these populations and results from several studies suggest that high white rice consumption increases T2D risk. We assessed whether rice, noodles and bread intake was associated with T2D risk in an ethnic Chinese population. METHODS: We included data from 45,411 male and female Chinese participants of the Singapore Chinese Health Study cohort aged 45-74 years at baseline. Usual diet at baseline was evaluated by a validated 165-item semi-quantitative food frequency questionnaire. Physician-diagnosed T2D was self-reported during two follow-up interviews. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a mean follow-up of 11 years, 5207 incident cases of T2D were documented. Rice intake was not associated with higher T2D risk [HR for extreme quintiles, 0.98 (95% CI 0.90, 1.08)] despite the large variation in intake levels (median intake for extreme quintiles: 236.5 g/day vs. 649.3 g/day), although the precise risk estimate depended greatly on the substitute food. Replacing one daily serving of rice with noodles [HR 1.14 (95% CI 1.07, 1.22)], red meat [HR 1.40 (95% CI 1.23, 1.60)] and poultry [HR 1.37 (95% CI 1.18, 1.59)] was associated with higher T2D risk, whereas the replacement of rice with white bread [HR 0.90 (95% CI 0.85, 0.94)] or wholemeal bread [HR 0.82 (95% CI 0.75, 0.90)] was associated with lower T2D risk. CONCLUSIONS: Higher rice consumption was not substantially associated with a higher risk of T2D in this Chinese population. Recommendations to reduce high white rice consumption in Asian populations for the prevention of T2D may only be effective if substitute foods are considered carefully. KEYWORDS: Bread; Grains; Noodles; Refined grains; Rice; Type 2 diabetes Parrot Genomes and the Evolution of Heightened Longevity and Cognition. Wirthlin M, Lima NCB, Guedes RLM, Soares AER, Almeida LGP, Cavaleiro NP, Loss de Morais G, Chaves AV, Howard JT, Teixeira MM, Schneider PN, Santos FR, Schatz MC, Felipe MS, Miyaki CY, Aleixo A, Schneider MPC, Jarvis ED, Vasconcelos ATR, Prosdocimi F, Mello CV. Curr Biol. 2018 Nov 28. pii: S0960-9822(18)31417-9. doi: 10.1016/j.cub.2018.10.050. [Epub ahead of print] PMID: 30528582 Abstract Parrots are one of the most distinct and intriguing groups of birds, with highly expanded brains [1], highly developed cognitive [2] and vocal communication [3] skills, and a long lifespan compared to other similar-sized birds [4]. Yet the genetic basis of these traits remains largely unidentified. To address this question, we have generated a high-coverage, annotated assembly of the genome of the blue-fronted Amazon (Amazona aestiva) and carried out extensive comparative analyses with 30 other avian species, including 4 additional parrots. We identified several genomic features unique to parrots, including parrot-specific novel genes and parrot-specific modifications to coding and regulatory sequences of existing genes. We also discovered genomic features under strong selection in parrots and other long-lived birds, including genes previously associated with lifespan determination as well as several hundred new candidate genes. These genes support a range of cellular functions, including telomerase activity; DNA damage repair; control of cell proliferation, cancer, and immunity; and anti-oxidative mechanisms. We also identified brain-expressed, parrot-specific paralogs with known functions in neural development or vocal-learning brain circuits. Intriguingly, parrot-specific changes in conserved regulatory sequences were overwhelmingly associated with genes that are linked to cognitive abilities and have undergone similar selection in the human lineage, suggesting convergent evolution. These findings bring novel insights into the genetics and evolution of longevity and cognition, as well as provide novel targets for exploring the mechanistic basis of these traits. KEYWORDS: Amazona aestiva; Psittaciformes; cognition; evolution; genome; genomics; longevity; parrot; telomerase; ultraconserved elements
  10. AlPater

    Al's CR updates

    mTOR, glycotoxins and the parallel universe. Green AS. Aging (Albany NY). 2018 Dec 12. doi: 10.18632/aging.101720. [Epub ahead of print] No abstract available. PMID: 30540565 KEYWORDS: advance glycation end products; aging; food restriction; rapamycin https://www.aging-us.com/article/101720/text Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice. Antunes MM, de Almeida-Souza CB, Godoy G, Crisma AR, Masi LN, Curi R, Bazotte RB. Braz J Med Biol Res. 2018 Dec 10;52(1):e8150. doi: 10.1590/1414-431X20188150. PMID: 30539971 Abstract High caloric intake promotes chronic inflammation, insulin resistance, and chronic diseases such as type-2 diabetes, which may be prevented by food restriction (FR). The effect of FR on expression of pro-inflammatory and anti-inflammatory genes in adipose tissue, liver, muscle, and brain was compared. Male Swiss mice were submitted to FR (FR group) or had free access to food (control group) during 56 days. The liver, gastrocnemius muscle, brain, and epididymal white adipose tissue (WAT) were collected for analysis of gene expressions. FR attenuated inflammation in the liver, brain, and gastrocnemius muscle but did not markedly change inflammatory gene expression in epididymal WAT. We concluded that adipose tissue was less responsive to FR in terms of gene expression of pro-inflammatory and anti-inflammatory genes. Caloric restriction rescues yeast cells from alpha-synuclein toxicity through autophagic control of proteostasis. Sampaio-Marques B, Pereira H, Santos AR, Teixeira A, Ludovico P. Aging (Albany NY). 2018 Dec 7. doi: 10.18632/aging.101675. [Epub ahead of print] PMID: 30530923 Abstract α-Synuclein (SNCA) is a presynaptic protein that is associated with the pathophysiology of synucleinopathies, including Parkinson's disease. SNCA is a naturally aggregation-prone protein, which may be degraded by the ubiquitin-proteasome system (UPS) and by lysosomal degradation pathways. Besides being a target of the proteolytic systems, SNCA can also alter the function of these pathways further, contributing to the progression of neurodegeneration. Deterioration of UPS and autophagy activities with aging further aggravates this toxic cycle. Caloric restriction (CR) is still the most effective non-genetic intervention promoting lifespan extension. It is known that CR-mediated lifespan extension is linked to the regulation of proteolytic systems, but the mechanisms underlying CR rescue of SNCA toxicity remain poorly understood. This study shows that CR balances UPS and autophagy activities during aging. CR enhances UPS activity, reversing the decline of the UPS activity promoted by SNCA, and keeps autophagy at homeostatic levels. Maintenance of autophagy at homeostatic levels appears to be relevant for UPS activity and for the mechanism underlying rescue of cells from SNCA-mediated toxicity by CR. KEYWORDS: aging; alpha-synuclein; autophagy; caloric restriction; ubiquitin-proteasome system Effects of caloric restriction on neuropathic pain, peripheral nerve degeneration and inflammation in normometabolic and autophagy defective prediabetic Ambra1 mice. Coccurello R, Nazio F, Rossi C, De Angelis F, Vacca V, Giacovazzo G, Procacci P, Magnaghi V, Ciavardelli D, Marinelli S. PLoS One. 2018 Dec 10;13(12):e0208596. doi: 10.1371/journal.pone.0208596. eCollection 2018. PMID: 30532260 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208596 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0208596&type=printable Abstract There is a growing interest on the role of autophagy in diabetes pathophysiology, where development of neuropathy is one of the most frequent comorbidities. We have previously demonstrated that neuropathic pain after nerve damage is exacerbated in autophagy-defective heterozygous Ambra1 mice. Here, we show the existence of a prediabetic state in Ambra1 mice, characterized by hyperglycemia, intolerance to glucose and insulin resistance. Thus, we further investigate the hypothesis that prediabetes may account for the exacerbation of allodynia and chronic pain and that counteracting the autophagy deficit may relieve the neuropathic condition. We took advantage from caloric restriction (CR) able to exert a double action: a powerful increase of autophagy and a control on the metabolic status. We found that CR ameliorates neuropathy throughout anti-inflammatory and metabolic mechanisms both in Ambra1 and in WT animals subjected to nerve injury. Moreover, we discovered that nerve lesion represents, per se, a metabolic stressor and CR reinstates glucose homeostasis, insulin resistance, incomplete fatty acid oxidation and energy metabolism. As autophagy inducer, CR promotes and anticipates Schwann cell autophagy via AMP-activated protein kinase (AMPK) that facilitates remyelination in peripheral nerve. In summary, we provide new evidence for the role of autophagy in glucose metabolism and identify in energy depletion by dietary restriction a therapeutic approach in the fight against neuropathic pain. Common polymorphism in the cannabinoid receptor gene type 2 (CB2R) rs3123554 are associated with metabolic changes after two different hypocaloric diets with different dietary fatty profiles. Aller R, Primo D, Izaola O, de Luis DA. Clin Nutr. 2018 Nov 30. pii: S0261-5614(18)32546-9. doi: 10.1016/j.clnu.2018.11.013. [Epub ahead of print] PMID: 30528951 Abstract BACKGROUND: The role of CB2R gene variants on weight loss after a dietary intervention has been investigated in few studies. OBJECTIVE: We evaluate the effect of this genetic variant (rs3123554) of CB2R gene on cardiovascular risk factors and weight loss secondary to high monounsaturated fat vs a high polyunsaturated fat hypocaloric diets. DESIGN: A Caucasian population of 362 obese patients was enrolled. Patients were randomly allocated during 3 months to one of two diets (Diet P high polyunsaturated (PUFAs) fat hypocaloric diet vs, Diet M high monounsaturated (MUFAs) fat hypocaloric diet). RESULTS: In both genotype groups (GG vs GA+AA), body weight, body mass index (BMI), fat mass, waist circumference and systolic blood pressure decreased after diet P and M. Body weight, BMI, fat mass and waist circumference were higher in A allele carriers than non A allele carriers. The improvement of these parameters was higher in non A allele carriers than A allele carriers. In non A allele carriers with both diets, the decrease of total cholesterol, LDL-cholesterol, insulin and HOMA-IR was higher than A allele carriers after both diets. After diet P, triglyceride levels decrease in non A allele carriers. CONCLUSION: Our data suggest that carriers of the minor allele of rs3123554 variant of CB2R gene lose less body weight during to different hypocaloric diets with different fatty acid. Moreover, non A-allele carriers showed a better response of LDL-cholesterol, HOMA-IR and insulin levels than A-carriers with both hypocaloric diets. KEYWORDS: Cannabinoid receptor gene type 2; Hypocaloric diet; Lipid profile; Obesity; rs3123554 DECEMBER 10, 2018 BY PORTSMOUTH DAILY TIMES High carb diet makes mice live longer https://www.portsmouth-dailytimes.com/opinion/33551/high-carb-diet-makes-mice-live-longer >>>>>>>>>>>>>>>> Comparing the Effects of Low-Protein and High-Carbohydrate Diets and Caloric Restriction on Brain Aging in Mice. Wahl D, Solon-Biet SM, Wang QP, Wali JA, Pulpitel T, Clark X, Raubenheimer D, Senior AM, Sinclair DA, Cooney GJ, de Cabo R, Cogger VC, Simpson SJ, Le Couteur DG. Cell Rep. 2018 Nov 20;25(8):2234-2243.e6. doi: 10.1016/j.celrep.2018.10.070. PMID: 30463018 Free Article https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31674-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124718316747%3Fshowall%3Dtrue Abstract Calorie restriction (CR) increases lifespan and improves brain health in mice. Ad libitum low-protein, high-carbohydrate (LPHC) diets also extend lifespan, but it is not known whether they are beneficial for brain health. We compared hippocampus biology and memory in mice subjected to 20% CR or provided ad libitum access to one of three LPHC diets or to a control diet. Patterns of RNA expression in the hippocampus of 15-month-old mice were similar between mice fed CR and LPHC diets when we looked at genes associated with longevity, cytokines, and dendrite morphogenesis. Nutrient-sensing proteins, including SIRT1, mTOR, and PGC1α, were also influenced by diet; however, the effects varied by sex. CR and LPHC diets were associated with increased dendritic spines in dentate gyrus neurons. Mice fed CR and LPHC diets had modest improvements in the Barnes maze and novel object recognition. LPHC diets recapitulate some of the benefits of CR on brain aging. KEYWORDS: brain aging; calorie restriction; cardiometabolic health; cognitive function; hippocampus; protein restriction
  11. Todd Allen

    Living for millions of years is possible

    I was wondering about that myself. I'd like to know how one measures how long something has been alive. I've know radio-carbon dating is fairly good for measuring how long something has been dead, assuming the living organism was largely composed of recently atmospheric carbon which probably isn't true of these bacteria. So it probably involves some other radio isotope(s) but I don't have a clue which ones or how/why. Perhaps it is? I don't think we have managed to probe very deeply there yet.
  12. Saul

    Living for millions of years is possible

    I believe it. But I don't think they have a good QOL. 😉
  13. Gordo

    Living for millions of years is possible

    I'm skeptical of their (unexplained) lifespan estimates, but interesting content nonetheless, you would think mars' interior should be teeming with life unless Earth is some miraculous exception (given that Mars' surface was carved out by water and water is very likely below the surface).
  14. Saul

    98.6 F (37.0 C) is old school

    Hi Matt! Warren gave up CR; but I'm pretty sure he still shares an apartment with Khurram.
  15. " Abstract Lifespan extension under low temperature is well conserved across both endothermic and exothermic taxa, but the mechanism underlying this change in aging is poorly understood. Low temperature is thought to decrease metabolic rate, thus slowing the accumulation of cellular damage from reactive oxygen species, although recent evidence suggests involvement of specific cold-sensing biochemical pathways. We tested the effect of low temperature on aging in 11 strains of Brachionus rotifers, with the hypothesis that if the mechanism of lifespan extension is purely thermodynamic, all strains should have a similar increase in lifespan. We found differences in change in median lifespan ranging from a 6% decrease to a 100% increase, as well as differences in maximum and relative lifespan extension and in mortality rate. Low temperature delays reproductive senescence in most strains, suggesting an extension of healthspan, even in strains with little to no change in lifespan. The combination of low temperature and caloric restriction in one strain resulted in an additive lifespan increase, indicating these interventions may work via non- or partially-overlapping pathways. The known low temperature sensor TRPA1 is present in the rotifer genome, but chemical TRPA1 agonists did not affect lifespan, suggesting that this gene may be involved in low temperature sensation but not in chemoreception in rotifers. The congeneric variability in response to low temperature suggests that the mechanism of low temperature lifespan extension is an active genetic process rather than a passive thermodynamic one and is dependent upon genotype." https://www.sciencedaily.com/releases/2018/12/181210171847.htm https://www.sciencedirect.com/science/article/pii/S0531556518305011?via%3Dihub
  16. for zombie bacteria... The discovery of what has been termed a "subterranean Galapagos" was announced by the Deep Carbon Observatory Tuesday, which said many of the lifeforms have lifespans of millions of years. https://www.cnn.com/2018/12/11/world/deep-carbon-observatory-zombie-carbon-intl/index.html and the quoted report from the Deep Carbon Observatory: https://deepcarbon.net/life-deep-earth-totals-15-23-billion-tonnes-carbon
  17. Matt

    98.6 F (37.0 C) is old school

    What happened to your website, Khuram? I remember reading it a long time ago, I think you had information about your diet, supplements and other things? But wow, yeah, that is very strict! @Saul What happened to Warren? It seems like a lot of people from the email lists never joined the forum...
  18. mccoy

    CR with ZeroCarb

    An interesting excerpt from a Mc Dougall's talk on eskimos. From the cited articles, eskimos suffer(ed) premature death by atherosclerosis and other CV diseases, plus osteoporosis and parasitic infections. An example of evolutionary adaptation but not an example of health and longevity...
  19. Veganism, vegetarianism, bone mineral density, and fracture risk: a systematic review and meta-analysis. Iguacel I, Miguel-Berges ML, Gómez-Bruton A, Moreno LA, Julián C. Nutr Rev. 2019 Jan 1;77(1):1-18. doi: 10.1093/nutrit/nuy045. PMID: 30376075 [Free pdf Production in progress] Abstract CONTEXT: The numbers of vegans and vegetarians have increased in the last decades. However, the impact of these diets on bone health is still under debate. OBJECTIVE: This systematic review and meta-analysis sought to study the impact of vegetarian and vegan diets on bone mineral density (BMD) and fracture risk. DATA SOURCES: A systematic search was conducted of PubMed, Scopus, and Science Direct, covering the period from the respective start date of each database to November 2017. DATA EXTRACTION: Two investigators evaluated 275 studies against the inclusion criteria (original studies in humans, written in English or Spanish and including vegetarian or vegan diets and omnivorous diets as factors with BMD values for the whole body, lumbar spine, or femoral neck and/or the number of fractures as the outcome) and exclusion criteria (articles that did not include imaging or studies that included participants who had suffered a fracture before starting the vegetarian or vegan diet). The quality assessment tool for observational cohort and cross-sectional studies was used to assess the quality of the studies. RESULTS: Twenty studies including 37 134 participants met the inclusion criteria. Compared with omnivores, vegetarians and vegans had lower BMD at the femoral neck and lumbar spine and vegans also had higher fracture rates. CONCLUSIONS: Vegetarian and vegan diets should be planned to avoid negative consequences on bone health. Resveratrol supplementation significantly influences obesity measures: a systematic review and dose-response meta-analysis of randomized controlled trials. Mousavi SM, Milajerdi A, Sheikhi A, Kord-Varkaneh H, Feinle-Bisset C, Larijani B, Esmaillzadeh A. Obes Rev. 2018 Dec 5. doi: 10.1111/obr.12775. [Epub ahead of print] Review. PMID: 30515938 Abstract This study aimed to summarize earlier randomized controlled trials on the effects of resveratrol supplementation on body weight (BW), body mass index (BMI), waist circumference (WC) and fat mass (FM). We searched PubMed, SCOPUS, Cochrane Library and Google Scholar from inception to April 2018 using relevant keywords. All clinical trials investigating the effects of resveratrol supplementation on BW, BMI, WC and FM in adults were included. Overall, 28 trials were included. Pooled effect sizes suggested a significant effect of resveratrol administration on weight (weighted mean differences [WMD]: -0.51 kg, 95% confidence interval [CI]: -0.94 to -0.09; I2 = 50.3%, P = 0.02), BMI (WMD: -0.17 kg m-2 , 95% CI: -0.32, -0.03; I2 = 49.6%, P = 0.02) and WC (WMD: -0.79 cm, 95% CI: -1.39, -0.2; I2 = 13.4%, P = 0.009), respectively. However, no significant effect of resveratrol supplementation on FM was found (WMD: -0.36%, 95% CI: -0.88, 0.15; I2 = 0.0%, P = 0.16). Findings from subgroup analysis revealed a significant reduction in BW and BMI in trials using resveratrol at the dosage of <500 mg d-1 , those with long-term interventions (≥3 month), and performed on people with obesity. Taken together, the data suggest that resveratrol supplementation has beneficial effects to reduce BW, BMI and WC, but not FM. KEYWORDS: dose-response; meta-analysis; obesity; resveratrol; weight Effect of S-equol and soy isoflavones on heart and brain. Sekikawa A, Ihara M, Lopez O, Kakuta C, Lopresti B, Higashiyama A, Aizenstein H, Chang YF, Mathis C, Miyamoto Y, Kuller L, Cui C. Curr Cardiol Rev. 2018 Dec 4. doi: 10.2174/1573403X15666181205104717. [Epub ahead of print] PMID: 30516108 Abstract BACKGROUND: Observational studies in Asia show that dietary intake of soy isoflavones had a significant inverse association with coronary heart disease (CHD). A recent randomized controlled trial (RCT) of soy isoflavones on atherosclerosis in the US, however, failed to show their benefit. The discrepancy may be due to the much lower prevalence of S-equol producers in Westerners: Only 20-30% of Westerners produce S-equol in contrast to 50-70% in Asians. S-equol is a metabolite of dietary soy isoflavone daidzein by gut microbiome and possesses the most anti-atherogenic properties among all isoflavones. Several short-duration RCTs documented that soy isoflavones improves arterial stiffness. Accumulating evidence shows that both atherosclerosis and arterial stiffness are positively associated with cognitive decline/dementia. Therefore, potentially, soy isoflavones, especially S-equol, are protective against cognitive decline/dementia. METHODS/RESULTS: This narrative review of clinical and epidemiological studies provides an overview of the health benefits of soy isoflavones and introduces S-equol. Second, we review recent evidence on the association of soy isoflavones and S-equol with CHD, atherosclerosis, and arterial stiffness as well as the association of atherosclerosis and arterial stiffness with cognitive decline/dementia. Third, we highlight recent studies that report the association of soy isoflavones and S-equol with cognitive decline/dementia. Lastly, we discuss the future directions of clinical and epidemiological research on the relationship of S-equol and CHD and dementia. CONCLUSIONS: Evidence from observational studies and short-term RCTs suggests that S-equol is anti-atherogenic and improves arterial stiffness and may prevent CHD and cognitive impairment/dementia. Well-designed long-term (≥ 2years) RCTs should be pursued. Association of Periodontal Disease and Edentulism With Hypertension Risk in Postmenopausal Women. Gordon JH, LaMonte MJ, Zhao J, Genco RJ, Cimato TR, Hovey KM, Allison MA, Mouton CP, Wactawski-Wende J. Am J Hypertens. 2018 Dec 4. doi: 10.1093/ajh/hpy164. [Epub ahead of print] PMID: 30517596 Abstract BACKGROUND: Multiple cross-sectional epidemiologic studies have suggested an association between periodontal disease and tooth loss and hypertension, but the temporality of these associations remains unclear. The objective of our study was to evaluate the association of baseline self-reported periodontal disease and edentulism with incident hypertension. METHODS: Study participants were 36,692 postmenopausal women in the Women's Health Initiative-Observational Study who were followed annually from initial periodontal assessment (1998-2003) through 2015 (mean follow-up 8.3 years) for newly diagnosed treated hypertension. Cox proportional hazards regression with adjustment for potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Edentulism was significantly associated with incident hypertension in crude (HR (95% CI) = 1.38 (1.28-1.49)) and adjusted (HR (95% CI) = 1.21 (1.11-1.30)) models. This association was stronger among those <60 years compared to ≥60 years (P interaction 0.04) and among those with <120 mm Hg systolic blood pressure, compared to those with ≥120 mm Hg (P interaction 0.004). No association was found between periodontal disease and hypertension. CONCLUSIONS: These findings suggest that edentulous postmenopausal women may represent a group with higher risk of developing future hypertension. As such improved dental hygiene among those at risk for tooth loss as well as preventive measures among the edentulous such as closer blood pressure monitoring, dietary modification, physical activity, and weight loss may be warranted to reduce disease burden of hypertension. Further studies are needed to clarify these results and further elucidate a potential role of periodontal conditions on hypertension risk. Errors in estimating usual sodium intake by the Kawasaki formula alter its relationship with mortality: implications for public health. He FJ, Campbell NRC, Ma Y, MacGregor GA, Cogswell ME, Cook NR. Int J Epidemiol. 2018 Dec 1;47(6):1784-1795. doi: 10.1093/ije/dyy114. PMID: 30517688 Abstract BACKGROUND: Several cohort studies with inaccurate estimates of sodium reported a J-shaped relationship with mortality. We compared various estimated sodium intakes with that measured by the gold-standard method of multiple non-consecutive 24-h urine collections and assessed their relationship with mortality. METHODS: We analysed the Trials of Hypertension Prevention follow-up data. Sodium intake was assessed in four ways: (i) average measured (gold standard): mean of three to seven 24-h urinary sodium measurements during the trial periods; (ii) average estimated: mean of three to seven estimated 24-h urinary sodium excretions from sodium concentration of 24-h urine using the Kawasaki formula; (iii) first measured: 24-h urinary sodium measured at the beginning of each trial; (iv) first estimated: 24-h urinary sodium estimated from sodium concentration of the first 24-h urine using the Kawasaki formula. We included 2974 individuals aged 30-54 years with pre-hypertension, not assigned to sodium intervention. RESULTS: During a median follow-up of 24 years, 272 deaths occurred. The average sodium intake measured by the gold-standard method was 3769 ± 1282 mg/d. The average estimated sodium over-estimated the intake by 1297 mg/d (95% confidence interval: 1267-1326). The average estimated value was systematically biased with over-estimation at lower levels and under-estimation at higher levels. The average measured sodium showed a linear relationship with mortality. The average estimated sodium appeared to show a J-shaped relationship with mortality. The first measured and the first estimated sodium both flattened the relationship. CONCLUSIONS: Accurately measured sodium intake showed a linear relationship with mortality. Inaccurately estimated sodium changed the relationship and could explain much of the paradoxical J-shaped findings reported in some cohort studies. Unsaturated Fatty Acid Intakes During Midlife Are Positively Associated with Later Cognitive Function in Older Adults with Modulating Effects of Antioxidant Supplementation. Assmann KE, Adjibade M, Hercberg S, Galan P, Kesse-Guyot E. J Nutr. 2018 Dec 1;148(12):1938-1945. doi: 10.1093/jn/nxy206. PMID: 30517725 https://sci-hub.tw/10.1093/jn/nxy206 Abstract BACKGROUND: Given the drastic demographic changes characterized as "population aging," the disease burden related to dementia is a major public health problem. The scientific literature documenting the link between mono- and polyunsaturated fatty acids (MUFAs, PUFAs) and cognitive function during aging is plentiful, but findings are inconsistent. OBJECTIVES: We aimed to evaluate the association between intakes of unsaturated fatty acids at midlife and cognitive performance 13 y later in French adults, and to test for a modulating effect of antioxidant supplementation. METHODS: Fatty acid intakes were estimated with the use of repeated 24-h records (1994-1996) among 3362 subjects (mean ± SD age: 65.5 ± 4.6 y) of the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study, including an intervention phase (1994-2002) during which participants were randomly assigned to an "antioxidant supplementation" or placebo group. Cognitive performance was assessed at follow-up only (in 2007-2009) via a battery of 6 standardized neuropsychological tests. A global cognitive score was calculated as the sum of T-scores of the 6 tests. Multivariable-adjusted regression analyses were performed to provide regression coefficients and 95% CIs. RESULTS: In multivariable models, total MUFAs, total PUFAs, and n-6 PUFAs (ω-6 PUFAs) were positively associated with overall cognitive functioning. n-3 PUFA (ω-3 PUFA) intakes showed positive associations among supplemented participants only (mean difference Tertile3 versus Tertile1: 1.40; 95% CI: 0.30, 2.51; P-trend = 0.01, P-interaction = 0.01). A detrimental role of arachidonic acid for cognitive functioning was only detected in the placebo group (mean difference Tertile3 versus Tertile1: -1.38; 95% CI: -2.57, -0.18; P-trend = 0.02, P-interaction = 0.07). CONCLUSION: Whereas higher total MUFA and n-6 PUFA intakes may be generally beneficial for maintaining cognitive health during aging, a higher consumption of n-3 fatty acids may only be beneficial among individuals with an adequate antioxidant status. These findings underline the importance of not only focusing on specific nutrients for dementia prevention, but also considering the complex interaction between consumed nutrients. Protein Intake and Risk of Falls: A Prospective Analysis in Older Adults. Sandoval-Insausti H, Pérez-Tasigchana RF, López-García E, Banegas JR, Rodríguez-Artalejo F, Guallar-Castillón P. J Am Geriatr Soc. 2018 Dec 5. doi: 10.1111/jgs.15681. [Epub ahead of print] PMID: 30517767 Abstract BACKGROUND: The prospective association between protein intake and falls has been little studied. We assessed this association in a Spanish community-dwelling cohort. METHODS: We performed a prospective cohort study of 2464 men and women 60 years or older who were recruited in 2008-2010 and followed up through 2012. At baseline, the habitual protein intake was determined with a validated dietary history. At the end of follow-up, participants reported the number of falls experienced in the preceding year. Participants were stratified by an unintentional weight loss of 4.5 kg or more. Logistic regression was used after adjustment for the main confounders. RESULTS: A total of 522 participants (21.2%) experienced at least one fall. The odds ratios (ORs) and 95% confidence intervals (CIs) of falling for the three increasing tertiles of total protein intake were 1.00, 0.86 (0.66-1.11), and 0.93 (0.70-1.24) (p for trend = 0.14). However, a statistically significant interaction with unintentional weight loss was observed for the association between protein intake and fall risk (p for interaction = 0.004). Among 163 participants (6.6%) who experienced unintentional weight loss, the ORs (95% CI) of falling for the three increasing tertiles of total protein intake were 1.00, 0.68 (0.21-2.23), and 0.23 (0.05-1.08) (p for trend = 0.01). CONCLUSION: No protective association between protein intake and fall risk in older adults was found. However, high total protein intake tended to confer substantial benefits to participants who experienced an unintentional weight loss of 4.5 kg or more in the preceding year. KEYWORDS: animal protein intake; falls; older adults; protein intake; unintentional weight loss; vegetable protein intake Contributions of a high-fat diet to Alzheimer's disease-related decline: A longitudinal behavioural and structural neuroimaging study in mouse models. Rollins CPE, Gallino D, Kong V, Ayranci G, Devenyi GA, Germann J, Chakravarty MM. Neuroimage Clin. 2018 Nov 20. pii: S2213-1582(18)30354-1. doi: 10.1016/j.nicl.2018.11.016. [Epub ahead of print] PMID: 30503215 https://www.sciencedirect.com/science/article/pii/S2213158218303541?via%3Dihub https://ac.els-cdn.com/S2213158218303541/1-s2.0-S2213158218303541-main.pdf?_tid=2cb122d9-52c7-496d-ac9c-1ae8896cdffb&acdnat=1544455370_7792bb8ae70e168218db56e8d000532d Abstract Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported that obesity accelerates AD-related pathophysiology and memory impairment in mouse models of AD. However, the nature of the brain structure-behaviour relationship mediating this acceleration remains unclear. In this manuscript we evaluated the impact of adolescent obesity on the brain morphology of the triple transgenic mouse model of AD (3xTg) and a non-transgenic control model of the same background strain (B6129s) using longitudinally acquired structural magnetic resonance imaging (MRI). At 8 weeks of age, animals were placed on a high-fat diet (HFD) or an ingredient-equivalent control diet (CD). Structural images were acquired at 8, 16, and 24 weeks. At 25 weeks, animals underwent the novel object recognition (NOR) task and the Morris water maze (MWM) to assess short-term non-associative memory and spatial memory, respectively. All analyses were carried out across four groups: B6129s-CD and -HFD and 3xTg-CD and -HFD. Neuroanatomical changes in MRI-derived brain morphology were assessed using volumetric and deformation-based analyses. HFD-induced obesity during adolescence exacerbated brain volume alterations by adult life in the 3xTg mouse model in comparison to control-fed mice and mediated volumetric alterations of select brain regions, such as the hippocampus. Further, HFD-induced obesity aggravated memory in all mice, lowering certain memory measures of B6129s control mice to the level of 3xTg mice maintained on a CD. Moreover, decline in the volumetric trajectories of hippocampal regions for all mice were associated with the degree of spatial memory impairments on the MWM. Our results suggest that obesity may interact with the brain changes associated with AD-related pathology in the 3xTg mouse model to aggravate brain atrophy and memory impairments and similarly impair brain structural integrity and memory capacity of non-transgenic mice. Further insight into this process may have significant implications in the development of lifestyle interventions for treatment of AD.
  20. Earlier
  21. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KH, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Cochrane Database Syst Rev. 2018 Nov 30;11:CD003177. doi: 10.1002/14651858.CD003177.pub4. Review. PMID: 30521670 Abstract BACKGROUND: Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES: To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. MAIN RESULTS: We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5g/d LCn3 to > 5 g/d (16 RCTs gave at least 3g/d LCn3).Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs) and ALA may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence with greater effects in trials at low summary risk of bias), and probably reduces risk of arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression.There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, except LCn3 reduced triglycerides by ˜15% in a dose-dependant way (high-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event and arrhythmia risk. Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index: A Secondary Analysis of a Randomized Clinical Trial and Observational Study. Iyengar NM, Arthur R, Manson JE, Chlebowski RT, Kroenke CH, Peterson L, Cheng TD, Feliciano EC, Lane D, Luo J, Nassir R, Pan K, Wassertheil-Smoller S, Kamensky V, Rohan TE, Dannenberg AJ. JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5327. [Epub ahead of print] PMID: 30520976 Abstract IMPORTANCE: Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown. OBJECTIVE: To investigate the association between body fat and breast cancer risk in women with normal BMI. DESIGN, SETTING, AND PARTICIPANTS: This ad hoc secondary analysis of the Women's Health Initiative (WHI) clinical trial and observational study cohorts was restricted to postmenopausal participants with a BMI ranging from 18.5 to 24.9. Women aged 50 to 79 years were enrolled from October 1, 1993, through December 31, 1998. Of these, 3460 participants underwent body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up. At a median follow-up of 16 years (range, 9-20 years), 182 incident breast cancers had been ascertained, and 146 were ER positive. Follow-up was complete on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018. MAIN OUTCOMES AND MEASURES: Body fat levels were measured at baseline and years 1, 3, 6, and 9 using DXA. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analyte levels were measured in subsets of participants. RESULTS: Among the 3460 women included in the analysis (mean [SD] age, 63.6 [7.6] years), multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass. The corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively. Similar positive associations were observed for serial DXA measurements in time-dependent covariate analyses. Circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher, whereas levels of high-density lipoprotein cholesterol and sex hormone-binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass. CONCLUSIONS AND RELEVANCE: In postmenopausal women with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women. Effect of a Whey Protein Supplement on Preservation of Fat Free Mass in Overweight and Obese Individuals on an Energy Restricted Very Low Caloric Diet. Larsen AE, Bibby BM, Hansen M. Nutrients. 2018 Dec 4;10(12). pii: E1918. doi: 10.3390/nu10121918. PMID: 30518130 Abstract The obesity epidemic has caused a widespread interest in strategies to achieve a healthy "high quality" weight loss, where excess fat is lost, while fat free mass (FFM) is preserved. In this study, we aimed to examine the effect of whey protein supplementation given before night sleep on FFM preservation during a 4-week (wk) period on a very low caloric diet (VLCD). Twenty-nine obese subjects (body mass index (BMI) > 28 kg/m²) completed a 4-week intervention including a VLCD and a walking program (30 min walking × 5 times per week). Subjects were randomly assigned to either control (CON, n = 15) or a whey protein supplement (PRO, 0.4 g protein/kg/day, n = 14), ingested before bedtime. Body composition (dual-energy X-ray absorptiometry, DXA), blood analysis and physical test were performed pre and post intervention. We measured nitrogen excretion in three 24 h urine collections (Day 0, 7 and 28) to assess nitrogen balance. Changes in nitrogen balance (NB) after 7 and 28 days was different between treatment groups (interaction p < 0.05). PRO was in NB after 7 days and in positive NB at day 28. In contrast, CON was in negative NB at day 7, but in NB at day 28. Nevertheless, no significant group differences were observed in the change in pre- and post-FFM measurements (-2.5 kg, [95% CI: 1.9; 3.1], p = 0.65). In conclusion, ingestion of a whey protein supplement before bedtime during a 4-week period on a VLCD improved nitrogen balance, but did not lead to any significant improvement in the quality of the weight loss in regard to observed changes in body composition and health parameters compared with controls. KEYWORDS: FFM; VLCD; body composition; protein supplement; weight loss Three-Year Chronic Consumption of Low-Carbohydrate Diet Impairs Exercise Performance and Has a Small Unfavorable Effect on Lipid Profile in Middle-Aged Men. Pilis K, Pilis A, Stec K, Pilis W, Langfort J, Letkiewicz S, Michalski C, Czuba M, Zych M, Chalimoniuk M. Nutrients. 2018 Dec 4;10(12). pii: E1914. doi: 10.3390/nu10121914. PMID: 30518095 https://www.mdpi.com/2072-6643/10/12/1914/htm Abstract The objective of this research was to determine whether chronic (average 3.58 ± 1.56 years) deliberate adherence to low carbohydrate diets (LCDs) is associated with selected markers of metabolism, risk factors of cardiovascular disease (CVD), body mass and physical performance in apparently healthy middle-aged men (n = 12). The control group comprised age, body mass and height matched men using mixed diets (MDs). The diets used were registered for 7 days and analyzed in terms of the energy, carbohydrate, fat and protein contents. It was found that the diets used were isoenergetic, yet varied considerably in carbohydrate and fat content. The LCDs significantly intensified the ketogenesis process, increased resting blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and heart rate, (HR) and decreased respiratory exchange ratio (RER) in relation to MD subjects. An exercise trial revealed significant impairment of exercise in subjects following the LCDs. The results showed that in the case where the subjects of two investigated groups did not differ in their somatic variables, long-term adherence to the LCDs was associated with substantially reduced exercise performance in apparently healthy subjects, along with an association with a small unfavorable effect on their lipid profile. KEYWORDS: carbohydrate restriction; cardiovascular disease; diets; men; metabolism Effects of Arachidonic and Docosohexahenoic Acid Supplementation during Gestation in Rats. Implication of Placental Oxidative Stress. Reyes-Hernández CG, Ramiro-Cortijo D, Rodríguez-Rodríguez P, Giambelluca S, Simonato M, González MDC, López de Pablo AL, López-Giménez MDR, Cogo P, Sáenz de Pipaón M, Carnielli VP, Arribas SM. Int J Mol Sci. 2018 Dec 4;19(12). pii: E3863. doi: 10.3390/ijms19123863. PMID: 30518038 https://www.mdpi.com/1422-0067/19/12/3863/htm Abstract Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA and DHA availability in plasma and placenta, (2) fetal growth, and (3) placental oxidative stress, analyzing the influence of sex. Experimental diet (ED) was prepared by substituting soybean oil in the control diet (CD) by a fungi/algae-based oil containing ARA and DHA (2:1). Rats were fed with CD or ED during gestation; plasma, placenta, and fetuses were obtained at gestational day 20. DHA, ARA, and their precursors were analyzed in maternal plasma and placenta by gas chromatography/mass spectrophotometry. Fetuses and placentas were weighed, the proportion of fetuses with intrauterine growth restriction (IUGR) determined, and placental lipid and protein oxidation analyzed. ED fetuses exhibited lower body weight compared to CD, being >40% IUGR; fetal weight negatively correlated with maternal plasma ARA, but not DHA. Only ED female placenta exhibited higher lipid and protein oxidation compared to its CD counterparts; lipid peroxidation is negatively associated with fetal weight. In conclusion, high ARA during gestation associates with IUGR, through placental oxidative stress, with females being more susceptible. KEYWORDS: ARA; DHA; IUGR; fetus; oxidative stress; placenta Implications of amino acid sensing and dietary protein to the aging process. Lushchak O, Strilbytska OM, Yurkevych I, Vaiserman AM, Storey KB. Exp Gerontol. 2018 Nov 28. pii: S0531-5565(18)30467-4. doi: 10.1016/j.exger.2018.11.021. [Epub ahead of print] Review. PMID: 30502540 https://sci-hub.tw/10.1016/j.exger.2018.11.021 Abstract Every organism must adapt and respond appropriately to the source of nutrients available in its environment. Different mechanisms and pathways are involved in detecting the intracellular and extracellular levels of macronutrients including amino acids. Detection of amino acids in food sources is provided by taste cells expressing T1R1 and T1R3 type receptors. Additionally, cells of the intestine, pancreas or heart sense amino acids extracellularly. Neuronal and hormonal regulation integrates and coordinates the signals at the organismal level. Amino acid-sensitive mechanisms including GCN2 protein, mTOR and LYNUS machinery adjust cellular process according to the availability of specific amino acids. Triggering these mechanisms by genetic manipulations or by external manipulations with diets has a significant impact on lifespan. In model organisms, the restriction of protein or specific amino acids within the diet leads to lifespan-extending effects. However, the translation of results from model organisms to application in humans has to take into account lifestyle, psychology, social aspects and the possibility to choose what to eat and how it is cooked. KEYWORDS: Aging; Amino acids; Macronutrients; Sensing https://nepis.epa.gov/Exe/ZyPDF.cgi/9100RY6A.PDF?Dockey=9100RY6A.PDF >>>>>>>>>>>>>>>>>>>>>> Dietary cadmium and risk of breast cancer subtypes defined by hormone receptor status: a prospective cohort study. Grioni S, Agnoli C, Krogh V, Pala V, Rinaldi S, Vinceti M, Contiero P, Vescovi L, Malavolti M, Sieri S. Int J Cancer. 2018 Dec 4. doi: 10.1002/ijc.32039. [Epub ahead of print] PMID: 30515770 Abstract Diet is the primary source of cadmium - a proven Group 1 human carcinogen - for non-smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results. We examined the association between dietary cadmium and risk of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR) and HER2 status, in 8,924 women recruited to a prospective study between 1987 and 1992. Dietary cadmium intake was estimated using a semi-quantitative food frequency questionnaire at baseline. During a median of 22 years of follow-up, 451 incident cases of breast cancer were identified through the Varese Cancer Registry. Multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer and receptor-defined breast cancer subtypes were estimated for quintiles of dietary cadmium intake, adjusting for confounding factors. Mean dietary cadmium intake was 7.8 (standard deviation 1.4) μg/day. Women with highest quintile of cadmium intake had a greater risk of breast cancer (HR 1.54; 95% CI, 1.06 - 2.22; p-trend = 0.028) than those with lowest quintile of intake. Women premenopausal at recruitment had HR = 1.73 (95% CI, 1.10 - 2.71, highest vs. lowest quintile); postmenopausal women had HR = 1.32 (95% CI, 1.05 - 1.66 for each standard deviation increase in cadmium). Cadmium-related risk of breast cancer did not vary with ER, PR or HER2 status (p-heterogeneity not significant). These findings support the hypothesis that dietary cadmium is a risk factor for breast cancer. This article is protected by copyright. All rights reserved. KEYWORDS: Cadmium; HER2; breast cancer; estrogen receptors; progesterone receptors
  22. AlPater

    Al's CR updates

    Role of the variant in adiponectin gene rs266729 on weight loss and cardiovascular risk factors after a hypocaloric diet with the Mediterranean pattern. de Luis DA, Primo D, Izaola O, Gomez Hoyos E, Lopez Gomez JJ, Ortola A, Aller R. Nutrition. 2018 Aug 23;60:1-5. doi: 10.1016/j.nut.2018.08.018. [Epub ahead of print] PMID: 30508762 https://sci-hub.tw/10.1016/j.nut.2018.08.018 Abstract OBJECTIVES: The role of ADIPOQ gene variants on weight loss after a dietary intervention remain unclear. The aim of this study was to analyze the effects of rs266729 of the ADIPOQ gene on cardiovascular risk factors and adiposity parameters after adherence to a Mediterranean-type hypocaloric diet. METHOD: Eighty-three obese patients were studied before and after 12 wk on a Mediterranean-type hypocaloric diet. Anthropometric parameters and biochemical profiles were measured. The variant of ADIPOQ gene rs266729 was assessed at basal time by polymerase chain reaction at real time. RESULTS: Two genotype groups were realized (CC versus CG + GG). The final genotype distribution was 48 patients CC (57.8%), 30 patients CG (36.2%) and 5 patients GG (6%). After dietary intervention with a moderate calorie restriction and in both genotypes, body mass index (BMI), weight, fat mass, systolic blood pressure, and waist circumference decreased. After dietary intervention and in non-G allele carriers (CC versus CG+ GG), glucose (δ: -6.2 ± 1.1 versus -2.9 ± 1.2 mg/dL; P = 0.02), total cholesterol (δ:-15.2 ± 3.1 versus -3.4 ± 2 mg/dL; P = 0.02), low-density lipoprotein cholesterol (δ, -14.9 ± 3.1 versus -4.9 ± 1.2 mg/dL; P = 0.01), insulin levels (δ, -4± 0.6 versus 0.7 ± 0.3 UI/L;P = 0.01), homeostasis model assessment for insulin resistance (δ, -1.6 ± 0.4 versus -0.2 ± 0.4 units; P = 0.01), and adiponectin (δ, -10.4 ± 3.1 versus -1.3 ± 1.0 ng/dL; P = 0.01) improved. CONCLUSION: After weight loss, the CC genotype of ADIPOQ gene variant (rs266729) is associated with increases in adiponectin levels and decreases of low-density lipoprotein cholesterol, insulin and homeostasis model assessment for insulin resistance after weight loss. KEYWORDS: Adipokines; Adiponectin gene; Cardiovascular risk factors; Hypocaloric diet; rs266729
  23. Saul

    98.6 F (37.0 C) is old school

    Hi Khuram! Indeed; IMO, you may be the most calorie restricted member of the CR Society. I remember meeting you and Warren at CR2. My eyes went wide -- I said to myself, ther is someone who is REALLY on CR! 😉 -- Saul
  24. KHashmi317

    98.6 F (37.0 C) is old school

    I've never been able to get really spectacular CR bios like testosterone, body temp, etc. At 1400 cal/day, 6 ft tall, and 115-20 lbs, my CR is (and has been) pretty hard-core -- for almost 19 years now..
  25. Saul

    98.6 F (37.0 C) is old school

    Out of curiosity, I used the oral temperature probe as an ear thermometer -- I inseted the probe into my ear canal. Result: 97.4. 🙄
  26. Saul

    98.6 F (37.0 C) is old school

    Oral temperature is what I take. Like the other methods, it has it's limitations. E.g., your temperature after a hot drink is artificially high; after a cold drink artificially low. Right now, I'm towards the end of the worst cold that I've had for a long time: oral temp is 98.1. Farhead temperature varies a lot also: If you test after coming in on a hot summer day, you get a high number; in midwinter, a low number. Ear temperature varies with where in the ear the probe is placed.
  27. Saul

    CR vs. common illness

    About the possible "gold nanoparticle test for cancer": As noted at the end of the newsclip: “As it stands it is just one more technological innovation that may or may not be useful in the clinical setting.” -- Saul
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