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  1. 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.
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    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.
  3. 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
  4. 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
  5. 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.
  6. 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
  7. 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
  8. AlPater

    Al's CR updates

    Healthy aging and the Mediterranean diet ROZALYN ANDERSON DECEMBER 3RD 2018 https://blog.oup.com/2018/12/healthy-aging-mediterranean-diet/ In this Q&A, Rozalyn Anderson, PhD and Co-Editor in Chief of the biological sciences section of The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, sits down with Luigi Fontana, PhD, and Mediterranean Diet expert. Dr. Luigi Fontana is well-known for his research focused primarily on healthy aging and longevity. His interest in this field began years ago in his native country, Italy, when he was practicing clinician in internal medicine. At that time in the late 1990s, the emphasis was primarily on diagnosis and treatment, not preventative care. Dr. Fontana was interested in following a different path. While working on his PhD in nutrition and metabolism, he reached out to international leaders in basic research focused on nutrition and health including Dr. Rick Weindruch, a leader in caloric restriction, and Dr. John Holloszy, an expert in exercise and health studies. For nearly 20 years since, Dr. Fontana has been engaged in aging and nutrition research at the Washington University School of Medicine. He has maintained research programs in the US and in Italy and has written extensively on nutrition and health. His newest adventure began in the summer of 2018 when he moved to Australia to work on a new initiative in health and aging at the University of Sydney. Rozalyn Anderson: How would you describe your perspective in aging research? Luigi Fontana: My emphasis is more toward nutrition and exercise than drug discovery. The goal is to identify the molecular determinants of aging and use that information to design diets, lifestyle strategies, and preventative interventions to ensure prolonged health into old age. RA: So one of the areas you are best known for is your work with people on the caloric restriction diet, what is the latest there? LF: It’s really amazing. We are now seeing people from the Caloric Restriction Society reach their 70s and 80s in robust health. Many of them at this age are active, prescription free, and still without complications of age-associated diseases and disorders. The diet is really delivering on the promise of healthy aging. RA: What do you see as the next steps? LF: We really need to know the framework of how diet influences aging and health. We need biomarkers of health and of risk for age-related conditions. With these tools, we can really appreciate the impact of nutrition on disease risk and figure out what works to promote healthy aging. At this stage, we are looking for alternate ways to enhance health. For example, it is possible to choose a diet that promotes health such as the Mediterranean Diet without actually doing full-blown caloric restriction. RA: So what are we talking about when we talk about the Mediterranean Diet? LF: A key feature of this health-promoting diet is that it is largely plant-based. The emphasis is on local fruit and vegetables, whole grains, beans, and nuts – with protein sources from grains, legumes, and fish, rather than red meat. A glass of wine taken with food is not unusual. Traditionally the diet is also associated with extra-virgin olive oil but there is a caveat here; in times gone by individuals on this kind of diet has an active lifestyle with physically demanding tasks being a routine day to day occurrence. The amount of food eaten must be matched to energy demands on the body, especially with the modern sedentary lifestyle, otherwise, the benefits may not be as strong. RA: How did you first learn about this diet? LF: When I was a child, I lived in a small town in the Dolomites close to Lake Garda. My mother became interested in what was known then as the macrobiotic diet, which basically has many commonalities with the Mediterranean Diet. We had a small garden and grew our own vegetables. You could say I have had a healthy diet since the very beginning. RA: There are a number of different diets out there, how do we know what will work? LF: There is really great support for health benefits of the Mediterranean diet, from epidemiology studies of large populations that are basically observational studies to randomized clinical trials that are strictly regulated studies. All the evidence suggests improvements in health from cognition, to cardiovascular disease, diabetes, and even cancer. Keep in mind though that for any diet to really be beneficial it has to be balanced with lifestyle and physical activity. RA: So how will we get to eventually seeing this work in clinical practice? LF: The current clinical paradigm waits until you are sick and then begins treating the condition. I really believe that the future of healthcare is going to be preventative medicine where the focus is on strategies to maintain health. To get there, basic research will be super important. This is the driving force to develop ideas and then we can test these ideas in human studies. Translatability is key but without basic science, we would have no leads to follow, it’s hard to see how any advances in human aging biology could be made without this foundational work. Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia. Sudo Y, Otsuka H, Miyakawa R, Goto A, Kashiwase Y, Terawaki K, Miyano K, Hirao Y, Taki K, Tagawa R, Kobayashi M, Okita N, Uezono Y, Higami Y. Int J Mol Sci. 2018 Dec 3;19(12). pii: E3852. doi: 10.3390/ijms19123852. PMID: 30513935 https://www.mdpi.com/1422-0067/19/12/3852/htm Abstract Despite the similar phenotypes, including weight loss, reduction of food intake, and lower adiposity, associated with caloric restriction (CR) and cancer cachexia (CC), CC is a progressive wasting syndrome, while mild CR improves whole body metabolism. In the present study, we compared adipose metabolic changes in a novel rat model of CC, mild CR (70% of the food intake of control rats, which is similar to the food consumption of CC rats), and severe CR (30% of the food intake of controls). We show that CC and severe CR are associated with much smaller adipocytes with significantly lower mitochondrial DNA content; but, that mild CR is not. CC and both mild and severe CR similarly upregulated proteins involved in lipolysis. CC also downregulated proteins involved in fatty acid biosynthesis, but mild CR upregulated these. These findings suggest that CC might impair de novo fatty acid biosynthesis and reduce mitochondrial biogenesis, similar to severe CR. We also found that rikkunshito, a traditional Japanese herbal medicine, does not ameliorate the enhanced lipolysis and mitochondrial impairment, but rather, rescues de novo fatty acid biosynthesis, suggesting that rikkunshito administration might have partially similar effects to mild CR. KEYWORDS: caloric restriction; cancer cachexia; rikkunshito; sterol regulatory element-binding transcription factor 1c Effects of intermittent versus continuous energy restriction for weight loss on diet quality and eating behavior. A randomized trial. Sundfør TM, Tonstad S, Svendsen M. Eur J Clin Nutr. 2018 Dec 4. doi: 10.1038/s41430-018-0370-0. [Epub ahead of print] PMID: 30514879 Abstract BACKGROUND/OBJECTIVES: Weight loss diets affect food choices and control of eating. We evaluated the effects of intermittent energy restriction (IER) vs. continuous energy restriction (CER) on nutritional composition and eating behavior. SUBJECT/METHODS: Individuals with BMI 30-45 kg/m2, abdominal obesity and ≥1 additional metabolic syndrome component were randomized to IER vs. CER with similar energy restriction. Of 112 participants, 98 completed weighed dietary records and the Three Factor Eating Questionnaire at baseline and three months. In statistical analysis, changes were adjusted for baseline values. RESULTS: Weight loss, energy intake, and macronutrient composition were similar in the IER and CER groups. The CER group reported a greater increase in fruit and berries (45 g/day [95% CI 21, 71] vs. 2 g/day [-28, 33]; p = 0.047) and vegetables (135 g/day [91, 179] vs. 65 g/day [35, 96]; p = 0.010) than the IER group. Fiber intake increased in the CER compared to the IER group (1.0 g/MJ/day [0.8, 1.2] vs. 0.2 [0.0, 0.4]; p < 0.001). Sugar intake was reduced in the CER compared to the IER group (-2.2E% [-3.2, -2.2] vs. -0.1E% [-1.2, 1.0]; p = 0.007). Intakes of folate, potassium, and magnesium decreased more in the IER than the CER group, while vitamin C increased more in the CER group (all p-values <0.014). Both diets improved eating behavior scores, but cognitive restraint increased more in the CER than the IER group (34 [30, 39] vs. 17 [12, 22]; p = 0.013). CONCLUSIONS: Men and women with obesity had more favorable changes in nutritional composition and eating behavior with CER than IER.
  9. Meal frequency and vegetable intake does not predict the development of frailty in older adults. Johannesson J, Rothenberg E, Gustafsson S, Slinde F. Nutr Health. 2018 Dec 5:260106018815224. doi: 10.1177/0260106018815224. [Epub ahead of print] PMID: 30514172 Abstract BACKGROUND:: Frailty is considered highly prevalent among the aging population. Fruit and vegetable intake is associated with positive health outcomes across the life-span; however, the relationship with health benefits among older adults has received little attention. AIM:: The aim was to examine if a relationship exists between meal frequency or frequency of vegetable intake and the development of frailty in a population of older adults. METHODS:: A total of 371 individuals, 80 years or older, from the study 'Elderly Persons in the Risk Zone' were included. Data was collected in the participants' home by face-to-face interviews up to 24 months after the intervention. Baseline data were calculated using Chi2-test; statistical significance was accepted at the 5% level. Binary logistic regression was used for the relationship between meal frequency or vegetable intake and frailty. RESULTS:: Mean meal frequency was 4.2 ± 0.9 meals per day; women seem to have a somewhat higher meal frequency than men (p=0.02); 57% of the participants had vegetables with at least one meal per day. No significant relationship was found between meal frequency or vegetable intake and frailty at 12 or 24 months follow-ups. CONCLUSIONS:: Among this group of older adults (80+), meal frequency was slightly higher among women than men, and just over half of the participants had vegetables with at least one meal a day. The risk of developing frailty was not associated with meal frequency or vegetable intake. The questions in this study were meant as indicators for healthy food habits. KEYWORDS: Aged 80 and older; community dwelling; frailty; meal frequency; vegetable intake 'I don't want to get old': Meet the 91-year-old who backflips off the high diving board Dubbed 'World's Most Extreme Grandpa' in viral video, John Carter of Trail, B.C., loves staying active Roshini Nair · CBC News · Posted: Dec 04, 2018 https://www.cbc.ca/news/canada/british-columbia/extreme-grandpa-backflips-diving-board-1.4932000 >>>>>>>>>>>>>>>>>> https://www.youtube.com/watch?v=CEySick9_Rw Plant-Based Diets: Considerations for Environmental Impact, Protein Quality, and Exercise Performance. Lynch H, Johnston C, Wharton C. Nutrients. 2018 Dec 1;10(12). pii: E1841. doi: 10.3390/nu10121841. Review. PMID: 30513704 https://www.mdpi.com/2072-6643/10/12/1841/htm Abstract Plant-based diets provide well-established physical and environmental health benefits. These benefits stem in part from the degree of restriction of animal-derived foods. Historically, meat and other animal-derived proteins have been viewed as an integral component of athletes' diets, leading some to question the adequacy of vegetarian or vegan diets for supporting athletic performance. The purpose of this review is to examine the impact of plant-based diets on human physical health, environmental sustainability, and exercise performance capacity. Based on currently available literature, it is unlikely that plant-based diets provide advantages, but do not suffer from disadvantages, compared to omnivorous diets for strength, anaerobic, or aerobic exercise performance. However, plant-based diets typically reduce the risk of developing numerous chronic diseases over the lifespan and require fewer natural resources for production compared to meat-containing diets. As such, plant-based diets appear to be viable options for adequately supporting athletic performance while concurrently contributing to overall physical and environmental health. Given the sparse literature comparing omnivore, vegetarian, and vegan athletes, particularly at the elite level, further research is warranted to ascertain differences that might appear at the highest levels of training and athletic performance. KEYWORDS: athlete; diet; exercise; health; nutrition; plant-based; protein; sustainability; vegan; vegetarian Plant-based diet and adiposity over time in a middle-aged and elderly population: the Rotterdam Study. Chen Z, Schoufour JD, Rivadeneira F, Lamballais S, Ikram MA, Franco OH, Voortman T. Epidemiology. 2018 Nov 30. doi: 10.1097/EDE.0000000000000961. [Epub ahead of print] PMID: 30507650 Abstract BACKGROUND: We aimed to explore whether adhering to a more plant-based diet, beyond strict vegan or vegetarian diets, may help prevent adiposity in a middle-aged and elderly population. METHODS: We included 9633 participants from the Rotterdam Study, a prospective cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline of three sub-cohorts of the Rotterdam Study (1989-93, 2000-01, 2006-08). We created a plant-based diet index by giving plant-based foods positive scores and animal-based foods reverse scores. A higher score on the index reflected an overall more plant-based and less animal-based diet. Data on anthropometrics and body composition (using dual energy X-ray absorptiometry) were collected every 3 to 5 years from 1989-2016. We used multivariable linear mixed models to analyze the associations. RESULTS: In the 9633 participants, baseline plant-based diet score ranged from 21.0 to 73.0 with a mean ± SD of 49.0 ± 7.0. In multivariable-adjusted analyses, higher adherence to a plant-based diet was associated with lower BMI, waist circumference, fat mass index, and body fat percentage across a median follow-up period of 7.1 years (per 10 points higher score, BMI: β= -0.70 kg/m, (95% CI -0.81, -0.59); waist circumference: -2.0 cm (-2.3, -1.7); fat mass index: -0.66 kg/m (-0.80, -0.52); body fat percentage: -1.1 points (-1.3, -0.84)). CONCLUSIONS: In this population-based cohort of middle-aged and elderly participants, a higher adherence to a more plant-based, less animal-based diet was associated with less adiposity over time, irrespective of general healthfulness of the specific plant- and animal-based foods. Serum gut microbe-dependent trimethylamine N-oxide improves the prediction of future cardiovascular disease in a community-based general population. Zheng L, Zheng J, Xie Y, Li Z, Guo X, Sun G, Sun Z, Xing F, Sun Y. Atherosclerosis. 2018 Nov 8;280:126-131. doi: 10.1016/j.atherosclerosis.2018.11.010. [Epub ahead of print] PMID: 30508691 https://sci-hub.tw/10.1016/j.atherosclerosis.2018.11.010 Abstract BACKGROUND AND AIMS: Recent studies have shown that trimethylamine N-oxide (TMAO) is a risk factor for cardiovascular disease (CVD) in different clinical settings, but few studies confirmed the association in a community-based general population. METHODS: This is a nested case-control study from a prospective cohort design. A total of 86 newly diagnosed CVD cases with a median follow-up period of 4.83 years and 86 matched controls were selected for the present analysis. RESULTS: Using the LC-MS/MS assays, we found that new CVD cases had a higher baseline levels of TMAO than controls [median (inter-quartile): 1.57 (0.79-2.29) μmol/L v.s 0.68 (0.23-1.40) μmol/L, p < 0.001]. After multivariable adjustment, individuals with TMAO ≥1.89 μmol/L (Q4) and 1.05-1.89 μmol/L (Q3) had odds ratio (OR) for CVD of 2.735 [95% confidence interval (CI): 1.328-5.630] and 2.544 (95% CI: 1.251-5.172) with the lowest quartile (<0.43 μmol/L) as reference. In addition, comparisons of areas under receiver operator characteristics curves confirmed that a model including TMAO had a better discrimination than one without (0.732 vs. 0.664, p = 0.045). CONCLUSIONS: In the community-based general population, there was a positive association between TMAO and future risk of CVD. Addition of TMAO improved the prediction of CVD beyond traditional risk factors. We recommend considering TMAO as a potential novel preventive target in the management of low-risk CVD adults. KEYWORDS: Cardiovascular disease; General population; Nested case-control study; Trimethylamine N-oxide Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients With Mild Hypertension. Sheppard JP, Stevens S, Stevens R, Martin U, Mant J, Hobbs FDR, McManus RJ. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4684. [Epub ahead of print] PMID: 30383082 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2708195?guestAccessKey=0215a663-f324-4bd3-bd21-f688e7028c06&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=etoc&utm_term=120518 Abstract IMPORTANCE: Evidence to support initiation of pharmacologic treatment in low-risk patients with mild hypertension is inconclusive, with previous trials underpowered to demonstrate benefit. Clinical guidelines across the world are contradictory. OBJECTIVE: To examine whether antihypertensive treatment is associated with a low risk of mortality and cardiovascular disease (CVD) in low-risk patients with mild hypertension. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal cohort study, data were extracted from the Clinical Practice Research Datalink, from January 1, 1998, through September 30, 2015, for patients aged 18 to 74 years who had mild hypertension (untreated blood pressure of 140/90-159/99 mm Hg) and no previous treatment. Anyone with a history of CVD or CVD risk factors was excluded. Patients exited the cohort if follow-up records became unavailable or they experienced an outcome of interest. EXPOSURES: Prescription of antihypertensive medication. Propensity scores for likelihood of treatment were constructed using a logistic regression model. Individuals treated within 12 months of diagnosis were matched to untreated patients by propensity score using the nearest-neighbor method. MAIN OUTCOMES AND MEASURES: The rates of mortality, CVD, and adverse events among patients prescribed antihypertensive treatment at baseline, compared with those who were not prescribed such treatment, using Cox proportional hazards regression. RESULTS: A total of 19 143 treated patients (mean [SD] age, 54.7 [11.8] years; 10 705 [55.9%] women; 10 629 [55.5%] white) were matched to 19 143 similar untreated patients (mean [SD] age, 54.9 [12.2] years; 10 631 [55.5%] female; 10 654 [55.7%] white). During a median follow-up period of 5.8 years (interquartile range, 2.6-9.0 years), no evidence of an association was found between antihypertensive treatment and mortality (hazard ratio {HR}, 1.02; 95% CI, 0.88-1.17) or between antihypertensive treatment and CVD (HR, 1.09; 95% CI, 0.95-1.25). Treatment was associated with an increased risk of adverse events, including hypotension (HR, 1.69; 95% CI, 1.30-2.20; number needed to harm at 10 years [NNH10], 41), syncope (HR, 1.28; 95% CI, 1.10-1.50; NNH10, 35), electrolyte abnormalities (HR, 1.72; 95% CI, 1.12-2.65; NNH10, 111), and acute kidney injury (HR, 1.37; 95% CI, 1.00-1.88; NNH10, 91). CONCLUSIONS AND RELEVANCE: This prespecified analysis found no evidence to support guideline recommendations that encourage initiation of treatment in patients with low-risk mild hypertension. There was evidence of an increased risk of adverse events, which suggests that physicians should exercise caution when following guidelines that generalize findings from trials conducted in high-risk individuals to those at lower risk. Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Santé Prospective Cohort Study. Baudry J, Assmann KE, Touvier M, Allès B, Seconda L, Latino-Martel P, Ezzedine K, Galan P, Hercberg S, Lairon D, Kesse-Guyot E. JAMA Intern Med. 2018 Oct 22. doi: 10.1001/jamainternmed.2018.4357. [Epub ahead of print] PMID: 30422212 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2707948?guestAccessKey=2e8694bf-5343-42e1-a7ad-097b04e4c114&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=etoc&utm_term=120518 Key Points Question What is the association between an organic food–based diet (ie, a diet less likely to contain pesticide residues) and cancer risk? Findings In a population-based cohort study of 68 946 French adults, a significant reduction in the risk of cancer was observed among high consumers of organic food. Meaning A higher frequency of organic food consumption was associated with a reduced risk of cancer; if the findings are confirmed, research investigating the underlying factors involved with this association is needed to implement adapted and targeted public health measures for cancer prevention. Abstract Importance Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk. Objective To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults. Design, Setting, and Participants In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016. Main Outcomes and Measures This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors. Results Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88; P for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96). Conclusions and Relevance A higher frequency of organic food consumption was associated with a reduced risk of cancer. If these findings are confirmed, further research is necessary to determine the underlying factors involved in this association. >>>>>>>>>>>>>>>>>>>>>> Organic Foods for Cancer Prevention-Worth the Investment? Hemler EC, Chavarro JE, Hu FB. JAMA Intern Med. 2018 Oct 22. doi: 10.1001/jamainternmed.2018.4363. [Epub ahead of print] No abstract available. PMID: 30422205 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2707943?guestAccessKey=c4e05604-c9f7-4c63-b6ba-0eaba017a6b7&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=etoc&utm_term=120518
  10. AlPater

    Al's CR updates

    Drosophila Gut-A Nexus Between Dietary Restriction and Lifespan. Lian T, Wu Q, Hodge BA, Wilson KA, Yu G, Yang M. Int J Mol Sci. 2018 Nov 29;19(12). pii: E3810. doi: 10.3390/ijms19123810. Review. PMID: 30501099 https://www.mdpi.com/1422-0067/19/12/3810/htm Abstract Aging is often defined as the accumulation of damage at the molecular and cellular levels which, over time, results in marked physiological impairments throughout the organism. Dietary restriction (DR) has been recognized as one of the strongest lifespan extending therapies observed in a wide array of organisms. Recent studies aimed at elucidating how DR promotes healthy aging have demonstrated a vital role of the digestive tract in mediating the beneficial effects of DR. Here, we review how dietary restriction influences gut metabolic homeostasis and immune function. Our discussion is focused on studies of the Drosophila digestive tract, where we describe in detail the potential mechanisms in which DR enhances maintenance of the intestinal epithelial barrier, up-regulates lipid metabolic processes, and improves the ability of the gut to deal with damage or stress. We also examine evidence of a tissue-tissue crosstalk between gut and neighboring organs including brain and fat body. Taken together, we argue that the Drosophila gut plays a critical role in DR-mediated lifespan extension. KEYWORDS: Drosophila; aging; dietary restriction; gut; intestinal epithelia barrier
  11. Reversibility of irreversible aging. Galkin F, Zhang B, Dmitriev SE, Gladyshev VN. Ageing Res Rev. 2018 Dec 1. pii: S1568-1637(18)30254-X. doi: 10.1016/j.arr.2018.11.008. [Epub ahead of print] Review. PMID: 30513346 https://sci-hub.tw/10.1016/j.arr.2018.11.008 Abstract Most multicellular organisms are known to age, due to accumulation of damage and other deleterious changes over time. These changes are often irreversible as organisms, humans included, evolved fully differentiated, irreplaceable cells (e.g. neurons) and structures (e.g. skeleton). Hence, deterioration or loss of at least some cells and structures should lead to inevitable aging of these organisms. Yet, some cells may escape this fate: adult somatic cells may be converted to partially reprogrammed cells or induced pluripotent stem cells (iPSCs). By their nature, iPSCs are the cells representing the early stages of life, indicating a possibility of reversing the age of cells within the organism. Reprogramming strategies may be accomplished both in vitro and in vivo, offering opportunities for rejuvenation in the context of whole organisms. Similarly, older organs may be replaced with the younger ones prepared ex vivo, or grown within other organisms or even other species. How could the irreversibility of aging of some parts of the organism be reconciled with the putative reversal of aging in the other parts of the same organism? Resolution of this question holds promise for dramatically extending lifespan, which is currently not possible with traditional genetic, dietary and pharmacological approaches. Critical issues in this challenge are the nature of aging, relationship between aging of an organism and aging of its parts, relationship between cell dedifferentiation and rejuvenation, and increased risk of cancer that goes hand in hand with rejuvenation approaches. Clinical evidence on the effects of saffron (Crocus sativus L.) on cardiovascular risk factors: A systematic review meta-analysis. Pourmasoumi M, Hadi A, Najafgholizadeh A, Kafeshani M, Sahebkar A. Pharmacol Res. 2018 Nov 28;139:348-359. doi: 10.1016/j.phrs.2018.11.038. [Epub ahead of print] Review. PMID: 30502528 Abstract Cardiovascular disease is a one of most common causes of mortality around the world. This meta-analysis aims to summarize and conclude the clinical evidence regarding the use of saffron and its constituents, in particular crocin, on cardiovascular risk factors. A systematic review was conducted with PubMed, Scopus, Web of Science, Cochrane library and Google Scholar up to 24 May 2018. Randomized controlled trials (RCTs) that assessed the clinical effects of saffron and/or its constituents on blood lipid profile, glycemic parameters, blood pressure and anthropometric indices in human subjects were included. Eleven publication from ten studies comprising 622 participants included in quantitative analysis. Pooling of results showed significant effect of saffron on diastolic blood pressure (-1.24 mmHg; 95% CI: -1.51 to -0.96; I2 = 0%), body weight (-1.29 kg; 95% CI: -2.14 to -0.44; I2 = 70%) and waist circumstance (-1.68 cm; 95% CI: -3.31 to -0.04; I2 = 51%). When subgroup analysis was performed based on quality of studies, a significant reduction in fasting plasma glucose levels was observed in subgroup with high quality studies (-10.14 mg/dl; 95% CI: -13.80 to -6.48; I2 = 0%). Meta-analysis did not reveal any significant change in lipid profile, fasting insulin, systolic blood pressure and body mass index following saffron consumption. Present meta-analysis suggests that saffron might be beneficial in several outcomes related with cardiovascular disease. However, further RCTs with long term intervention with different dose of administration are needed. KEYWORDS: Blood pressure; Body mass index; Fasting plasma glucose; Lipid profile; Meta-analysis; Saffron Dietary intervention with a specific micronutrient combination for the treatment of patients with cardiac arrhythmias: the impact on insulin resistance and left ventricular function. Parsi E, Bitterlich N, Winkelmann A, Rösler D, Metzner C. BMC Cardiovasc Disord. 2018 Dec 3;18(1):220. doi: 10.1186/s12872-018-0954-6. PMID: 30509185 https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0954-6 Abstract BACKGROUND: Cardiac arrhythmias (CA) are very common and may occur with or without heart disease. Causes of these disturbances can be components of the metabolic syndrome (MetS) or deficits of micronutrients especially magnesium, potassium, B vitamins and coenzyme Q10. Both causes may also influence each other. Insulin resistance (IR) is a risk factor for diastolic dysfunction. One exploratory outcome of the present pilot study was to assess the impact of a dietary intervention with specific micronutrients on the lowering of IR levels in patients with CA with the goal to improve the left ventricular (LV) function. METHODS: This was a post hoc analysis of the randomized double blind, placebo-controlled pilot study in patients with CA (VPBs, SVPBs, SV tachycardia), which were recruited using data from patients who were 18-75 years of age in an Outpatient Practice of Cardiology. These arrhythmias were assessed by Holter ECG and LV function by standard echocardiography. Glucose metabolism was measured by fasting glucose, fasting insulin level and the Homeostasis Model Assessment of IR (HOMA-IR) at baseline and after 6 weeks of dietary supplementation. RESULTS: A total of 54 randomized patients with CA received either a specific micronutrient combination or placebo. Dietary intervention led to a significant decrease in fasting insulin ≥58 pmol/l (p = 0.020), and HOMA-IR (p = 0.053) in the verum group after 6 weeks. At the same time, parameters of LV diastolic function were improved after intervention in the verum group: significant reduction of LV mass index (p = 0.003), and in tendency both a decrease of interventricular septal thickness (p = 0.053) as well as an increase of E/A ratio (p = 0.051). On the other hand, the premature beats (PBs) were unchanged under verum. CONCLUSIONS: In this pilot study, dietary intervention with specific micronutrient combination as add-on to concomitant cardiovascular drug treatment seems to improve cardio metabolic health in patients with CA. Further studies are required. STUDY REGISTRATION: The study was approved by the Freiburg Ethics Commission International and was retrospectively registered with the U.S. National Institutes of Health Clinical Trials gov ID NCT 02652338 on 16 December 2015. KEYWORDS: Diastolic LV function; Dietary intervention; Glucose metabolism; LVMI; Premature beats Postprandial energy expenditure of protein is affected by its phosphorus content. Abdouni L, Olabi A, Obeid O. J Therm Biol. 2018 Dec;78:214-218. doi: 10.1016/j.jtherbio.2018.10.013. Epub 2018 Oct 19. PMID: 30509638 Abstract Postprandial energy expenditure (PEE) is largely dependent on ATP production, which is may be affected by phosphorus (P) availability. Proteins are known to have high levels of P and induce high levels of PEE. This study aimed at assessing the effect of P in PEE of normal and high protein meals. A single-blind randomized crossover study was conducted with two groups of 12 healthy lean male subjects who received iso-caloric (554 Kcal) meals. Group1: normal protein (NPr) meal with or without P (500 mg) and group 2: high protein (HPr) meal with or without P (500 mg), on two visits separated by a minimum of 1-week washout period. Energy expenditure and substrate oxidation were measured at baseline and every 30 min for 4 h after meal ingestion using a ventilated hood for indirect calorimetry. NPr and HPr meals had similar postprandial energy expenditure and this was significantly increased (P = 0.005) by P ingestion. Our work shows that PEE of protein meal is highly affected by P content of the meal. KEYWORDS: High protein; Normal protein; Phosphorus; Postprandial energy expenditure Lowering effects of n-3 fatty acid supplements on blood pressure by reducing plasma angiotensin II in Inner Mongolia hypertensive patients: A double-blind randomized controlled trial。. Yang B, Shi L, Wang AM, Shi MQ, Li ZH, Zhao F, Guo XJ, Li D. J Agric Food Chem. 2018 Dec 4. doi: 10.1021/acs.jafc.8b05463. [Epub ahead of print] PMID: 30511840 Abstract Whether n-3 fatty acid (FA) has hypotensive actions among Chinese adults remains inconclusive. Hypertensive patients from Inner Mongolia, China (n=126) were recruited to a double-blind, randomized controlled trial. We investigated the effects of n-3 FA supplements on blood pressure (BP, mm Hg), plasma concentrations of angiotensin II (Ang II, pg/mL) and nitric oxygen (NO, µmol/L), using fish oil (n=41, 4 capsules/day, equivalent to 2 grams of eicosapentaenoic acid plus docosahexaenoic acid) and flaxseed oil (n=42, 4 capsules/day, equivalent to 2.5 grams of α-linolenic acid). Comparing to the control group (corn oil, n=43), the mean systolic BP (-4.52±9.28 vs. -1.51±9.23, P=0.040) and the plasma Ang II levels (-12.68±10.87 vs. -4.93±9.08, P=0.023) were significantly lowered in fish oil group, whereas diastolic BP (P=0.285) and plasma NO levels (P=0.220) were not. Such findings suggest that marine-based n-3 FA has a hypotensive efficacy in Chinese hypertensive patients possibly through inhibiting Ang II-dependent vasoconstrictions.
  12. AlPater

    Al's CR updates

    Obs Rev Volume 19, Issue S1Supplement: Targeting Lifestyle Energy Expenditure in Management of Obesity & Cardiometabolic Risks: from Biology to Built environment, 9th Fribourg Obesity Research Conference (FORC 2017), Held on October 19th 2017 at the Faculty of Science, University of Fribourg, Organised by Department of Medicine‐Physiology, University of Fribourg, Switzerland, In association with the Swiss Association for Study of Obesity, Guest Editor: Abdul G. DullooPages: 1-107December 2018>>>>>>>>>>>>>>>>>>>>>>>>>>>Regulation of intestinal growth in response to variations in energy supply and demand.Nilaweera KN, Speakman JR.Obes Rev. 2018 Dec;19 Suppl 1:61-72. doi: 10.1111/obr.12780. Review.PMID: 30511508https://sci-hub.tw/https://onlinelibrary.wiley.com/doi/abs/10.1111/obr.12780AbstractThe growth of the intestine requires energy, which is known to be met by catabolism of ingested nutrients. Paradoxically, during whole body energy deficit including calorie restriction, the intestine grows in size. To understand how and why this happens, we reviewed data from several animal models of energetic challenge. These were bariatric surgery, cold exposure, lactation, dietary whey protein intake and calorie restriction. Notably, these challenges all reduced the adipose tissue mass, altered hypothalamic neuropeptide expression and increased intestinal size. Based on these data, we propose that the loss of energy in the adipose tissue promotes the growth of the intestine via a signalling mechanism involving the hypothalamus. We discuss possible candidates in this pathway including data showing a correlative change in intestinal (ileal) expression of the cyclin D1 gene with adipose tissue mass, adipose derived-hormone leptin and hypothalamic expression of leptin receptor and the pro-opiomelanocortin gene. The ability of the intestine to grow in size during depletion of energy stores provides a mechanism to maximize assimilation of ingested energy and in turn sustain critical functions of tissues important for survival.KEYWORDS:adipose tissue; hypothalamus; intestine>>>>>>>>>>>>>>>>>>>>>>>>>>>>>Changes in physical activity over the lifespan: impact on body composition and sarcopenic obesity.Westerterp KR.Obes Rev. 2018 Dec;19 Suppl 1:8-13. doi: 10.1111/obr.12781. Review.PMID: 30511504https://sci-hub.tw/https://onlinelibrary.wiley.com/doi/abs/10.1111/obr.12781AbstractPhysical activity and body composition show a typical pattern over the lifecycle. Fat-free mass and physical performance generally peak in early adulthood. Here, evidence for a relation between physical activity changes over the life span and the development of sarcopenic obesity is presented. Activity-induced energy expenditure increases with body size and physical activity during growth. The physical activity level, calculated by expressing total energy expenditure as a multiple of resting energy expenditure, gradually increases from early age to adulthood to decrease again in old age. Habitual physical activity has a significant effect on growth of fat-free mass during adolescence and thus on peak fat-free mass and physical performance in early adulthood. Older subjects have a lower fat-free mass and lower physical activity levels but there is no association, suggesting physical activity does not protect against loss of lean body mass at higher age. Prevention of sarcopenic obesity starts with a physically active lifestyle to develop a healthy peak fat-free mass and subsequent prevention of excess fat gain. The change from a physically active to a more sedentary routine in later life requires restriction of energy intake to maintain energy balance.KEYWORDS:Fat-free mass; fat-free mass index; physical activity level; sarcopenic obesity>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>A systematic review of the separate and combined effects of energy restriction and exercise on fat-free mass in middle-aged and older adults: implications for sarcopenic obesity.Weinheimer EM, Sands LP, Campbell WW.Nutr Rev. 2010 Jul;68(7):375-88. doi: 10.1111/j.1753-4887.2010.00298.x. Review.PMID: 20591106https://sci-hub.tw/10.1111/j.1753-4887.2010.00298.xAbstractThe systematic review presented here assessed the effects of energy restriction (ER) and exercise (EX) on fat-free mass (FFM) in overweight and obese middle-aged and older adults. PubMed was searched using the key words "weight loss or energy restriction" AND "skeletal muscle or body composition," with limitations set for "human" and "middle-aged and aged." Results from 52 studies are reported as the percentages of EX (mainly aerobic training), ER, or ER+EX groups that had a specified change in body weight and FFM, since insufficient data were available for a meta-analysis. The EX groups had modest body weight and FFM changes. Eighty-one percent and 39% of the ER and ER+EX groups, respectively, lost > or = 15% of body weight as FFM. These findings suggest that exercise is an effective tool to help men and postmenopausal women aged > or = 50 years, with a BMI greater than 25 kg/m(2) preserve FFM after moderate ER-induced weight loss, which is important for combating sarcopenic obesity.>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>Rationale for novel intermittent dieting strategies to attenuate adaptive responses to energy restriction.Sainsbury A, Wood RE, Seimon RV, Hills AP, King NA, Gibson AA, Byrne NM.Obes Rev. 2018 Dec;19 Suppl 1:47-60. doi: 10.1111/obr.12787. Review.PMID: 30511512AbstractEating patterns involving intermittent energy restriction (IER) include 'intermittent fasting' where energy intake is severely restricted for several 'fasting' days per week, with 'refeeding' days (involving greater energy intake than during fasting days) at other times. Intermittent fasting does not improve weight loss compared to continuous energy restriction (CER), where energy intake is restricted every day. We hypothesize that weight loss from IER could be improved if refeeding phases involved restoration of energy balance (i.e. not ongoing energy restriction, as during intermittent fasting). There is some evidence in adults with overweight or obesity showing that maintenance of a lower weight may attenuate (completely or partially) some of the adaptive responses to energy restriction that oppose ongoing weight loss. Other studies show some adaptive responses persist unabated for years after weight loss. Only five randomized controlled trials in adults with overweight or obesity have compared CER with IER interventions that achieved energy balance (or absence of energy restriction) during refeeding phases. Two reported greater weight loss than CER, whereas three reported similar weight loss between interventions. While inconclusive, it is possible that achieving energy balance (i.e. avoiding energy restriction or energy excess) during refeeding phases may be important in realizing the potential of IER.KEYWORDS:Diet-reducing; intermittent energy restriction; intermittent fasting; obesity
  13. Your meals are speeding up climate change, but there's a way to eat sustainably 5 tips for trimming your culinary carbon footprint that don't involve going vegan Emily Chung · CBC News · Posted: Dec 04, 2018 https://www.cbc.ca/news/technology/food-climate-change-carbon-footprint-1.4930062 Optimal protein intake during pregnancy for reducing the risk of fetal growth restriction: the Japan Environment and Children's Study. Morisaki N, Nagata C, Yasuo S, Morokuma S, Kato K, Sanefuji M, Shibata E, Tsuji M, Senju A, Kawamoto T, Ohga S, Kusuhara K; Japan Environment and Children’s Study Group. Br J Nutr. 2018 Dec;120(12):1432-1440. doi: 10.1017/S000711451800291X. Epub 2018 Nov 5. PMID: 30394228 Abstract Clinical trials show that protein supplement increases infant size in malnourished populations; however, epidemiological studies in high-income countries have reported mixed results. Although these findings suggest a non-linear relationship between maternal macronutrient intake and fetal growth, this relationship has not been closely examined. We assessed the association between maternal protein intake and fetal growth among 91 637 Japanese women with singletons in a nation-wide cohort study using validated FFQ. The respondents answered the FFQ twice, once during early pregnancy (FFQ1; 16·3 (sd 6·0) weeks), and second during mid-pregnancy (FFQ2, 28·1 (sd 4·1) weeks). Daily energy intake and percentage energy from protein, fats and carbohydrates were 7477 (sd 2577) kJ and 13·5 (sd 2·0), 29·5 (sd 6·5) and 55·3 (sd 7·8) %, respectively, for FFQ1, and 7184 (sd 2506) kJ and 13·6 (sd 2·1), 29·8 (sd 6·6) and 55·3 (sd 7·9) %, respectively, for FFQ2. The average birth weight was 3028 (sd 406) g, and 6350 infants (6·9 %) were small for gestational age (SGA). In both phases of the survey, birth weight was highest and the risk of SGA was lowest when the percentage energy from protein was 12 %, regardless of whether isoenergetic replacement was with fat or carbohydrates. Furthermore, when protein density in the maternal diet was held constant, birth weight was highest when 25 % of energy intake came from fat and 61 % came from carbohydrates during early pregnancy. We found maternal protein intake to have an inverse U-curve relationship with fetal growth. Our results strongly suggest that the effect of protein on birth weight is non-linear, and that a balanced diet fulfilling the minimum requirement for all macronutrients was ideal for avoiding fetal growth restriction. KEYWORDS: JECS Japan Environment and Children’s Study; SGA small for gestational age; Fetal growth; Macronutrients; Maternal diet; Protein; Small-for-gestational age Effect of dietary interventions in mild cognitive impairment: a systematic review. McGrattan AM, McEvoy CT, McGuinness B, McKinley MC, Woodside JV. Br J Nutr. 2018 Dec;120(12):1388-1405. doi: 10.1017/S0007114518002945. Epub 2018 Nov 9. PMID: 30409231 Abstract Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed, particularly in a mild cognitive impairment (MCI) population. This review examined the effect of diet on cognitive outcomes in MCI patients. A total of five databases were searched to find randomised controlled trial (RCT) studies, with diet as the main focus, in MCI participants. The primary outcome was incident dementia and/or Alzheimer's disease (AD) and secondary outcomes included cognitive function across different domains using validated neuropsychological tests. Sixteen studies met the inclusion criteria. There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making study comparisons difficult. Supplementation with vitamin E (one study, n 516), ginkgo biloba (one study, n 482) or Fortasyn Connect (one study, n 311) had no significant effect on progression from MCI to dementia and/or AD. For cognitive function, the findings showed some improvements in performance, particularly in memory, with the most consistent results shown by B vitamins, including folic acid (one study, n 266), folic acid alone (one study, n 180), DHA and EPA (two studies, n 36 and n 86), DHA (one study, n 240) and flavonol supplementation (one study, n 90). The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients. Further well-designed trials are needed, with standardised and robust measures of cognition to investigate the influence of diet on cognitive status. KEYWORDS: AD Alzheimer’s disease; GI glycaemic index; HF high flavonol; HR hazard ratio; LF low flavonol; MCI mild cognitive impairment; MMSE Mini Mental State Examination; RCT randomised controlled trial; Diet; Interventions; Lifestyle; Mild cognitive impairment; Systematic reviews Involvement of calcium-sensing receptor activation in the alleviation of intestinal inflammation in a piglet model by dietary aromatic amino acid supplementation. Liu H, Tan B, Huang B, Li J, Wang J, Liao P, Guan G, Ji P, Yin Y. Br J Nutr. 2018 Dec;120(12):1321-1331. doi: 10.1017/S0007114518002891. Epub 2018 Oct 30. PMID: 30375295 https://sci-hub.tw/10.1017/S0007114518002891 Abstract Ca2+-sensing receptor (CaSR) represents a potential therapeutic target for inflammatory bowel diseases and strongly prefers aromatic amino acid ligands. We investigated the regulatory effects of dietary supplementation with aromatic amino acids - tryptophan, phenylalanine and tyrosine (TPT) - on the CaSR signalling pathway and intestinal inflammatory response. The in vivo study was conducted with weanling piglets using a 2 × 2 factorial arrangement in a randomised complete block design. Piglets were fed a basal diet or a basal diet supplemented with TPT and with or without inflammatory challenge. The in vitro study was performed in porcine intestinal epithelial cell line to investigate the effects of TPT on inflammatory response using NPS-2143 to inhibit CaSR. Dietary supplementation of TPT alleviated histopathological injury and decreased myeloperoxidase activity in intestine challenged with lipopolysaccharide. Dietary supplementation of TPT decreased serum concentration of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-12, granulocyte-macrophage colony-stimulating factor, TNF-α), as well as the mRNA abundances of pro-inflammatory cytokines in intestine but enhanced anti-inflammatory cytokines IL-4 and transforming growth factor-β mRNA levels compared with pigs fed control diet and infected by lipopolysaccharide. Supplementation of TPT increased CaSR and phospholipase Cβ2 protein levels, but decreased inhibitor of NF-κB kinase α/β and inhibitor of NF-κB (IκB) protein levels in the lipopolysaccharide-challenged piglets. When the CaSR signalling pathway was blocked by NPS-2143, supplementation of TPT decreased the CaSR protein level, but enhanced phosphorylated NF-κB and IκB levels in IPEC-J2 cells. To conclude, supplementation of aromatic amino acids alleviated intestinal inflammation as mediated through the CaSR signalling pathway. KEYWORDS: BW body weight; CCL2 CC chemokine ligand 2; CaSR calcium-sensing receptor; GM-CSF granulocyte–macrophage colony-stimulating factor; IKK inhibitor of NF-κB kinase; IκB inhibitor of NF-κB; LPS lipopolysaccharide; MCP monocyte chemoattractant protein; MPO myeloperoxidase; PLC phospholipase C; Phe phenylalanine; TGF transforming growth factor; TPT tryptophan phenylalanine and tyrosine; Trp tryptophan; Tyr tyrosine; p-NF-κB phosphorylated NF-κB; Aromatic amino acids; Calcium-sensing receptor; Inflammatory response; Piglet model
  14. AlPater

    Al's CR updates

    Low calorie dieting increases cortisol. Tomiyama AJ, Mann T, Vinas D, Hunger JM, Dejager J, Taylor SE. Psychosom Med. 2010 May;72(4):357-64. doi: 10.1097/PSY.0b013e3181d9523c. Epub 2010 Apr 5. PMID: 20368473 Free PMC Article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895000/pdf/nihms198826.pdf Abstract OBJECTIVE: To test the hypothesis that dieting, or the restriction of caloric intake, is ineffective because it increases chronic psychological stress and cortisol production--two factors that are known to cause weight gain; and to examine the respective roles of the two main behaviors that comprise dieting--monitoring one's caloric intake and restricting one's caloric intake--on psychological and biological stress indicators. METHODS: In a 2 (monitoring vs. not) x 2 (restricting vs. not) fully crossed, controlled experiment, 121 female participants were assigned randomly to one of four dietary interventions for 3 weeks. The monitoring + restricting condition tracked their caloric intake and restricted their caloric intake (1200 kcal/day); the monitoring only condition tracked their caloric intake but ate normally; the restricting only condition was provided 1200 kcal/day of food but did not track their calories, and the control group ate normally and did not track their intake. Before and after the interventions, participants completed measures of perceived stress and 2 days of diurnal saliva sampling to test for cortisol. RESULTS: Restricting calories increased the total output of cortisol, and monitoring calories increased perceived stress. CONCLUSIONS: Dieting may be deleterious to psychological well-being and biological functioning, and changes in clinical recommendations may be in order. >>>>>>>>>>>>>>>>>>>>> Psychosom Med. 2010 Jul;72(6):598-9; author reply 599-600. doi: 10.1097/PSY.0b013e3181e9df06. Epub 2010 Jul 1. Low-calorie dieting and dieters' cortisol levels: don't forget cortisone. Remer T, Shi L. PMID: 20595418 https://sci-hub.tw/10.1097/PSY.0b013e3181e9df06
  15. MIND Diet Associated with Reduced Incidence and Delayed Progression of ParkinsonismA in Old Age. Agarwal P, Wang Y, Buchman AS, Holland TM, Bennett DA, Morris MC. J Nutr Health Aging. 2018;22(10):1211-1215. doi: 10.1007/s12603-018-1094-5. PMID: 30498828 Abstract BACKGROUND: In old age, motor impairments including parkinsonian signs are common, but treatment is lacking for many older adults. In this study, we examined the association of a diet specifically developed to promote brain health, called MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), to the incidence and progression of parkinsonism in older adults. METHODS: A total of 706 Memory and Aging Project participants aged 59 -97 years and without parkinsonism at baseline were assessed annually for the presence of four parkinsonian signs using a 26-item modified version of the United Parkinson's Disease Rating Scale. Incident parkinsonism was defined as the first occurrence over 4.6 years of follow-up of two or more parkinsonian signs. The progression of parkinsonism was assessed by change in a global parkinsonian score (range: 0-100). MIND, Mediterranean, and DASH diet pattern scores were computed based on a validated food frequency questionnaire including 144 food items. We employed Cox-Proportional Hazard models and linear mixed models, to examine the associations of baseline diet scores with incident parkinsonism and the annual rate of change in global parkinsonian score, respectively. RESULTS: In models adjusted for age, sex, smoking, total energy intake, BMI and depressive symptoms, higher MIND diet scores were associated with a decreased risk of parkinsonism [(HR=0.89, 95% CI 0.83-0.96)]; and a slower rate of parkinsonism progression [(β= -0.008; SE=0.0037; p=0.04)]. The Mediterranean diet was marginally associated with reduced parkinsonism progression (β= -0.002; SE=0.0014; p=0.06). The DASH diet, by contrast, was not associated with either outcome. CONCLUSION: The MIND diet created for brain health may be a associated with decreased risk and slower progression of parkinsonism in older adults. KEYWORDS: MIND diet; Parkinsonism; dietary pattern; longitudinal; motor decline Health and sustainability outcomes of vegetarian dietary patterns: a revisit of the EPIC-Oxford and the Adventist Health Study-2 cohorts. Segovia-Siapco G, Sabaté J. Eur J Clin Nutr. 2018 Oct 2. doi: 10.1038/s41430-018-0310-z. [Epub ahead of print] Review. PMID: 30487555 Abstract Knowledge in the role of plant-based diets on health had been shaped in part by cohort studies on vegetarians. We revisited publications from two ongoing longitudinal studies comprising large proportions of vegetarians-the Adventist Health Study-2 (AHS-2) and the European Prospective Investigation into Cancer and Nutrition-Oxford (EPIC-Oxford)-to describe the food and nutrient intake, health effects, and environmental sustainability outcomes of the dietary patterns identified in these studies. The vegetarian diet groups in both cohorts have essentially no meat intake, lower intake of fish and coffee, and higher intakes of vegetables and fruits compared to their non-vegetarian counterparts. In the AHS-2 cohort, vegetarians have higher intake of whole grains, legumes, nuts, and seeds. Vegans in AHS-2 have 16% reduced risk while vegans, vegetarians, and fish-eaters in EPIC-Oxford have 11-19% lower risk for all cancers compared to non-vegetarians. Pesco-vegetarians in the AHS-2 cohort had significantly lower mortality risk from all causes and ischemic heart disease while EPIC-Oxford fish-eaters had significantly lower all-cancers mortality risk than their non-vegetarians counterparts. Morbidity risks and prevalence rates for other chronic diseases were differentially reported in the two cohorts but vegetarians have lower risk than non-vegetarians. Greenhouse gas emissions of equicaloric diets are 29% less in vegetarian diet in AHS-2 and 47-60% less for vegetarian/vegan diets in EPIC-Oxford than non-vegetarian/meat-eating diets. The beneficial health outcomes and reduced carbon footprints make the case for adoption of vegetarian diets to address global food supply and environmental sustainability. Dietary factors and risk of gout and hyperuricemia: a meta-analysis and systematic review. Li R, Yu K, Li C. Asia Pac J Clin Nutr. 2018;27(6):1344-1356. doi: 10.6133/apjcn.201811_27(6).0022. PMID: 30485934 Abstract BACKGROUND AND OBJECTIVES: To evaluate the associations of dietary factors and the risk of gout and hyperuricemia. METHODS AND STUDY DESIGN: PubMed and Embase databases were searched from inception to June 2017 for eligible studies. Nineteen prospective cohort or cross-sectional studies with adequate sample sizes are included, all involving red meat, seafoods, alcohol, fructose, dairy products, soy foods, high-purine vegetables and coffee. RESULTS: Meta-analysis revealed several dietary associations with gout risk: red meat: OR 1.29 (95% CI 1.16-1.44); seafoods: OR 1.31 (95% CI 1.01-1.68); alcohol: OR 2.58 (95% CI 1.81-3.66); fructose: OR 2.14 (95% CI 1.65- 2.78); dairy products: OR 0.56 (95% CI 0.44-0.70); soy foods: OR 0.85 (95% CI 0.76-0.96); high-purine vegetables: OR 0.86 (95% CI 0.75-0.98); coffee: OR 0.47 (95% CI 0.37-0.59).Dietary association with hyperuricemia risk (red meat: OR 1.24 (95% CI 1.04-1.48); seafoods: OR 1.47 (95% CI 1.16-1.86); alcohol: OR 2.06 (95% CI 1.60-2.67); fructose: OR 1.85 (95% CI 1.66-2.07); dairy products: OR 0.50 (95% CI 0.37-0.66); soy foods: OR 0.70 (95% CI 0.56-0.88); high-purine vegetables ingestion: OR 1.10 (95% CI 0.88-1.39), P=0.39; coffee:OR0.76 in men (95% CI 0.55-1.06), OR 1.58 in women (95% CI 1.16-2.16). CONCLUSION: The risk of hyperuricemia and gout is positively correlated with the intake of red meat, seafoods, alcohol or fructose, and negatively with dairy products or soy foods. High-purine vegetables showed no association with hyperuricemia, but negative association with gout. Coffee intake is negatively associated with gout risk, whereas it may be associated with increased hyperuricemia risk in women but decreased risk in men. Selenium and sex steroid hormones in a US nationally representative sample of men: A role for the link between selenium and estradiol in prostate carcinogenesis? Van Hemelrijck M, Sollie S, Nelson WG, Yager JD, Kanarek NF, Dobs A, Platz EA, Rohrmann S. Cancer Epidemiol Biomarkers Prev. 2018 Nov 27. pii: cebp.0520.2018. doi: 10.1158/1055-9965.EPI-18-0520. [Epub ahead of print] PMID: 30482876 http://sci-hub.tw/http://cebp.aacrjournals.org/content/early/2018/11/27/1055-9965.EPI-18-0520 Abstract BACKGROUND: Given the recent findings from pooled studies about a potential inverse association between selenium levels and prostate cancer risk, the current cross-sectional study aimed to investigate the association between serum selenium and serum concentrations of sex steroid hormones including estradiol in a nationally representative sample of US men to investigate one mechanism by which selenium may influence prostate cancer risk. METHODS: The study included 1,420 men aged 20 years or older who participated in the Third National Health and Nutrition Examination Survey (NHANES III) between 1988 and 1994. We calculated age/race-ethnicity-adjusted and multivariable-adjusted geometric mean serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide (AAG), and sex hormone binding globulin (SHBG) and compared them across quartiles of serum selenium. RESULTS: Adjusting for age, race/ethnicity, smoking status, serum cotinine, household income, physical activity, alcohol consumption and percent body fat, mean total estradiol (e.g. Q1:38.00 pg/mL (95%CI:36.03-40.08) vs Q4:35.29 pg/mL (33.53-37.14); Ptrend=0.050)and free estradiol [e.g.Q1: 0.96 pg/mL (95%CI: 0.92-1.01) vs Q4: 0.90 (95%CI:0.85-0.95); Ptrend=0.065] concentrations decreased over quartiles of selenium. Stratification by smoking and alcohol consumption, showed that the latter observation was stronger for never smokers (Pinteraction=0.073) and those with limited alcohol intake (Pinteraction=0.017). No associations were observed for the other sex steroid hormones studied. CONCLUSION: Our findings suggests that a possible mechanism by which selenium may be protective for prostate cancer is related to estrogen. IMPACT: Further studies of longitudinal measurements of serum and toenail selenium in relation to serum measurements of sex steroid hormones are needed. Consumption of individual saturated fatty acids and the risk of myocardial infarction in a UK and a Danish cohort. Praagman J, Vissers LET, Mulligan AA, Laursen ASD, Beulens JWJ, van der Schouw YT, Wareham NJ, Hansen CP, Khaw KT, Jakobsen MU, Sluijs I. Int J Cardiol. 2018 Oct 22. pii: S0167-5273(17)36973-5. doi: 10.1016/j.ijcard.2018.10.064. [Epub ahead of print] PMID: 30482628 https://sci-hub.tw/https://linkinghub.elsevier.com/retrieve/pii/S0167527317369735 Abstract BACKGROUND: The effect of individual saturated fatty acids (SFAs) on serum cholesterol levels depends on their carbon-chain length. Whether the association with myocardial infarction (MI) also differs across individual SFAs is unclear. We examined the association between consumption of individual SFAs, differing in chain lengths ranging from 4 through 18 carbons, and risk of MI. METHODS: We used data from 22,050 and 53,375 participants from EPIC-Norfolk (UK) and EPIC-Denmark, respectively. Baseline SFA intakes were assessed through validated, country-specific food frequency questionnaires. Cox regression analysis was used to estimate associations between intakes of individual SFAs and MI risk, for each cohort separately. RESULTS: During median follow-up times of 18.8 years in EPIC-Norfolk and 13.6 years in Denmark, respectively, 1204 and 2260 MI events occurred. Mean (±SD) total SFA intake was 13.3 (±3.5) en% in EPIC-Norfolk, and 12.5 (±2.6) en% in EPIC-Denmark. After multivariable adjustment, intakes of C12:0 (lauric acid) and C14:0 (myristic acid) inversely associated with MI risk in EPIC-Denmark (HR upper versus lowest quintile: 0.80 (95%CI: 0.66, 0.96) for both SFAs). Intakes in the third and fourth quintiles of C4:0-C10:0 also associated with lower MI risk in EPIC-Denmark. Moreover, substitution of C16:0 (palmitic acid) and C18:0 (stearic acid) with plant proteins resulted in a reduction of MI risk in EPIC-Denmark (HR per 1 energy%: 0.86 (95%CI: 0.78, 0.95) and 0.87 (95%CI: 0.79, 0.96) respectively). No such associations were found in EPIC-Norfolk. CONCLUSION: The results from the present study suggest that the association between SFA and MI risk depends on the carbon chain-length of the SFA. Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women's Health Across the Nation. Wang D, Jackson EA, Karvonen-Gutierrez CA, Elliott MR, Harlow SD, Hood MM, Derby CA, Sternfeld B, Janssen I, Crawford SL, Huang MH, El Khoudary SR, Chae CU, Baylin A. J Am Heart Assoc. 2018 Dec 4;7(23):e010405. doi: 10.1161/JAHA.118.010405. PMID: 30482079 https://www.ahajournals.org/doi/pdf/10.1161/JAHA.118.010405 Abstract Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women's Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA - IMT ), adventitial diameter ( CCA - AD ), and carotid plaque. The associations of average HLS with CCA - IMT and CCA - AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA - IMT and CCA - AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women. KEYWORDS: atherosclerosis; cardiovascular disease; lifestyle; risk factors; women Telomere length and telomerase activity in T cells are biomarkers of high-performing centenarians. Tedone E, Huang E, O'Hara R, Batten K, Ludlow AT, Lai TP, Arosio B, Mari D, Wright WE, Shay JW. Aging Cell. 2018 Nov 28:e12859. doi: 10.1111/acel.12859. [Epub ahead of print] PMID: 30488553 Abstract It is generally recognized that the function of the immune system declines with increased age and one of the major immune changes is impaired T-cell responses upon antigen presentation/stimulation. Some "high-performing" centenarians (100+ years old) are remarkably successful in escaping, or largely postponing, major age-related diseases. However, the majority of centenarians ("low-performing") have experienced these pathologies and are forced to reside in long-term nursing facilities. Previous studies have pooled all centenarians examining heterogeneous populations of resting/unstimulated peripheral blood mononuclear cells (PBMCs). T cells represent around 60% of PBMC and are in a quiescence state when unstimulated. However, upon stimulation, T cells rapidly divide and exhibit dramatic changes in gene expression. We have compared stimulated T-cell responses and identified a set of transcripts expressed in vitro that are dramatically different in high- vs. low-performing centenarians. We have also identified several other measurements that are different between high- and low-performing centenarians: (a) The amount of proliferation following in vitro stimulation is dramatically greater in high-performing centenarians compared to 67- to 83-year-old controls and low-performing centenarians; (b) telomere length is greater in the high-performing centenarians; and (c) telomerase activity following stimulation is greater in the high-performing centenarians. In addition, we have validated a number of genes whose expression is directly related to telomere length and these are potential fundamental biomarkers of aging that may influence the risk and progression of multiple aging conditions. KEYWORDS: centenarians; healthy aging; longevity; stimulated T cells; telomerase activity; telomeres Omega-6 fats for the primary and secondary prevention of cardiovascular disease. Hooper L, Al-Khudairy L, Abdelhamid AS, Rees K, Brainard JS, Brown TJ, Ajabnoor SM, O'Brien AT, Winstanley LE, Donaldson DH, Song F, Deane KH. Cochrane Database Syst Rev. 2018 Nov 29;11:CD011094. doi: 10.1002/14651858.CD011094.pub4. [Epub ahead of print] Review. PMID: 30488422 Abstract BACKGROUND: Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated. OBJECTIVES: To assess effects of increasing omega-6 fats (linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA)) on CVD and all-cause mortality. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to May 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher versus lower omega-6 fat intake in adults with or without CVD, assessing effects over at least 12 months. We included full texts, abstracts, trials registry entries and unpublished studies. Outcomes were all-cause mortality, CVD mortality, CVD events, risk factors (blood lipids, adiposity, blood pressure), and potential adverse events. We excluded trials where we could not separate omega-6 fat effects from those of other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias of included trials. We wrote to authors of included studies. Meta-analyses used random-effects analysis, while sensitivity analyses used fixed-effects and limited analyses to trials at low summary risk of bias. We assessed GRADE quality of evidence for 'Summary of findings' tables. MAIN RESULTS: We included 19 RCTs in 6461 participants who were followed for one to eight years. Seven trials assessed the effects of supplemental GLA and 12 of LA, none DGLA or AA; the omega-6 fats usually displaced dietary saturated or monounsaturated fats. We assessed three RCTs as being at low summary risk of bias.Primary outcomes: we found low-quality evidence that increased intake of omega-6 fats may make little or no difference to all-cause mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.12, 740 deaths, 4506 randomised, 10 trials) or CVD events (RR 0.97, 95% CI 0.81 to 1.15, 1404 people experienced events of 4962 randomised, 7 trials). We are uncertain whether increasing omega-6 fats affects CVD mortality (RR 1.09, 95% CI 0.76 to 1.55, 472 deaths, 4019 randomised, 7 trials), coronary heart disease events (RR 0.88, 95% CI 0.66 to 1.17, 1059 people with events of 3997 randomised, 7 trials), major adverse cardiac and cerebrovascular events (RR 0.84, 95% CI 0.59 to 1.20, 817 events, 2879 participants, 2 trials) or stroke (RR 1.36, 95% CI 0.45 to 4.11, 54 events, 3730 participants, 4 trials), as we assessed the evidence as being of very low quality. We found no evidence of dose-response or duration effects for any primary outcome, but there was a suggestion of greater protection in participants with lower baseline omega-6 intake across outcomes.Additional key outcomes: we found increased intake of omega-6 fats may reduce myocardial infarction (MI) risk (RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low-quality evidence). High-quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little in the long term (mean difference (MD) -0.33 mmol/L, 95% CI -0.50 to -0.16, I2 = 81%; heterogeneity partially explained by dose, 4280 participants, 10 trials). Increasing omega-6 fats probably has little or no effect on adiposity (body mass index (BMI) MD -0.20 kg/m2, 95% CI -0.56 to 0.16, 371 participants, 1 trial, moderate-quality evidence). It may make little or no difference to serum triglycerides (MD -0.01 mmol/L, 95% CI -0.23 to 0.21, 834 participants, 5 trials), HDL (MD -0.01 mmol/L, 95% CI -0.03 to 0.02, 1995 participants, 4 trials) or low-density lipoprotein (MD -0.04 mmol/L, 95% CI -0.21 to 0.14, 244 participants, 2 trials, low-quality evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity. Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease. Abdelhamid AS, Martin N, Bridges C, Brainard JS, Wang X, Brown TJ, Hanson S, Jimoh OF, Ajabnoor SM, Deane KH, Song F, Hooper L. Cochrane Database Syst Rev. 2018 Nov 27;11:CD012345. doi: 10.1002/14651858.CD012345.pub3. [Epub ahead of print] Review. PMID: 30484282 Abstract BACKGROUND: Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega-3 PUFA and plant oils in omega-6 PUFA. Evidence suggests that increasing PUFA-rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. OBJECTIVES: To assess effects of increasing total PUFA intake on cardiovascular disease and all-cause mortality, lipids and adiposity in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing higher with lower PUFA intakes in adults with or without cardiovascular disease that assessed effects over 12 months or longer. We included full texts, abstracts, trials registry entries and unpublished data. Outcomes were all-cause mortality, cardiovascular disease mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included trials for further data. Meta-analyses used random-effects analysis, sensitivity analyses included fixed-effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence. MAIN RESULTS: We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Eleven included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA.Increasing PUFA intake probably has little or no effect on all-cause mortality (risk 7.8% vs 7.6%, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 19,290 participants in 24 trials), but probably slightly reduces risk of coronary heart disease events from 14.2% to 12.3% (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants) and cardiovascular disease events from 14.6% to 13.0% (RR 0.89, 95% CI 0.79 to 1.01, 17,799 participants in 21 trials), all moderate-quality evidence. Increasing PUFA may slightly reduce risk of coronary heart disease death (6.6% to 6.1%, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) andstroke (1.2% to 1.1%, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants, though confidence intervals include important harms), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, 16 trials, 15,107 participants) all low-quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality.Increasing PUFA intake probably slightly decreases triglycerides (by 15%, MD -0.12 mmol/L, 95% CI -0.20 to -0.04, 20 trials, 3905 participants), but has little or no effect on total cholesterol (mean difference (MD) -0.12 mmol/L, 95% CI -0.23 to -0.02, 26 trials, 8072 participants), high-density lipoprotein (HDL) (MD -0.01 mmol/L, 95% CI -0.02 to 0.01, 18 trials, 4674 participants) or low-density lipoprotein (LDL) (MD -0.01 mmol/L, 95% CI -0.09 to 0.06, 15 trials, 3362 participants). Increasing PUFA probably has little or no effect on adiposity (body weight MD 0.76 kg, 95% CI 0.34 to 1.19, 12 trials, 7100 participants).Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. AUTHORS' CONCLUSIONS: This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all-cause or cardiovascular disease mortality. The mechanism may be via TG reduction. Mannose impairs tumour growth and enhances chemotherapy. Gonzalez PS, O'Prey J, Cardaci S, Barthet VJA, Sakamaki JI, Beaumatin F, Roseweir A, Gay DM, Mackay G, Malviya G, Kania E, Ritchie S, Baudot AD, Zunino B, Mrowinska A, Nixon C, Ennis D, Hoyle A, Millan D, McNeish IA, Sansom OJ, Edwards J, Ryan KM. Nature. 2018 Nov;563(7733):719-723. doi: 10.1038/s41586-018-0729-3. Epub 2018 Nov 21. PMID: 30464341 https://sci-hub.tw/10.1038/s41586-018-0729-3 Abstract It is now well established that tumours undergo changes in cellular metabolism1. As this can reveal tumour cell vulnerabilities and because many tumours exhibit enhanced glucose uptake2, we have been interested in how tumour cells respond to different forms of sugar. Here we report that the monosaccharide mannose causes growth retardation in several tumour types in vitro, and enhances cell death in response to major forms of chemotherapy. We then show that these effects also occur in vivo in mice following the oral administration of mannose, without significantly affecting the weight and health of the animals. Mechanistically, mannose is taken up by the same transporter(s) as glucose3 but accumulates as mannose-6-phosphate in cells, and this impairs the further metabolism of glucose in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway and glycan synthesis. As a result, the administration of mannose in combination with conventional chemotherapy affects levels of anti-apoptotic proteins of the Bcl-2 family, leading to sensitization to cell death. Finally we show that susceptibility to mannose is dependent on the levels of phosphomannose isomerase (PMI). Cells with low levels of PMI are sensitive to mannose, whereas cells with high levels are resistant, but can be made sensitive by RNA-interference-mediated depletion of the enzyme. In addition, we use tissue microarrays to show that PMI levels also vary greatly between different patients and different tumour types, indicating that PMI levels could be used as a biomarker to direct the successful administration of mannose. We consider that the administration of mannose could be a simple, safe and selective therapy in the treatment of cancer, and could be applicable to multiple tumour types. Optimum cutoff values of anthropometric indices of obesity for predicting hypertension: more than one decades of follow-up in an Iranian population. Ramezankhani A, Ehteshami-Afshar S, Hasheminia M, Hajebrahimi MA, Azizi F, Hadaegh F. J Hum Hypertens. 2018 Aug 6. doi: 10.1038/s41371-018-0093-7. [Epub ahead of print] PMID: 30082689 Abstract We determined cutoff points of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), for predicting hypertension in an Iranian population. Study sample included 6359 (3678 female) participants aged ≥20 and <60 years of a prospective cohort. The sex stratified multivariate hazard ratios (HRs) for all indices were estimated using Cox regression in two age groups (20-39 and 40-59 years). Receiver operating characteristic (ROC) was used to evaluate the predictive ability and determine the optimal cut-off values of the indices. In both genders and two age groups, the confounders adjusted HRs were significant for general and central obesity measures indices. AUCs of the indices were similar in men; however, among women 40-59 years, WC and WHtR had significantly higher AUC compared to BMI. Generally, the optimal cut-off values were higher in the 40-59 year age group. Optimal BMI, WC and WHR and WHtR cut-off values were 24.15 kg/m2, 90.5 cm, 0.90 and 0.49 among men, aged 20-39 years; the corresponding values were 28.41 kg/m2, 86.5 cm, 0.96 and 0.50 in men aged 40-59 years, respectively. In women, the aforementioned values were 26.38 kg/m2, 83.5 cm, 0.79 and 0.51 in the age group of 20-39 years, and 29.57 kg/m2, 90.5 cm, 0.88 and 0.59 in the 40-59 year age group, respectively. Our results suggest that gender and age differences in the association between anthropometric indices and hypertension should be considered.