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  1. Influence of genetic polymorphisms and habitual caffeine intake on the changes in blood pressure, pulse rate, and calculation speed after caffeine intake: A prospective, double blind, randomized trial in healthy volunteers. Yoshihara T, Zaitsu M, Shiraishi F, Arima H, Takahashi-Yanaga F, Arioka M, Kajioka S, Sasaguri T. J Pharmacol Sci. 2019 Feb 1. pii: S1347-8613(19)30011-8. doi: 10.1016/j.jphs.2019.01.006. [Epub ahead of print] PMID: 30773300 https://reader.elsevier.com/reader/sd/pii/S1347861319300118?token=186FBFAA7DE77CAE70F8110EF18B9BB41E8DB1583DDB42B5439CB6D1A3BBE6FC8DE780979B1B0DA274292395896C2BA2 Abstract The aim of this study was to investigate the contribution of gene polymorphisms, in combination with habitual caffeine consumption, to the effect of caffeine intake on hemodynamic and psychoactive parameters. A double-blind, prospective study was conducted with 201 healthy volunteers randomly allocated 2:1 to the caffeinated group (150 mL decaffeinated coffee with additional 200 mg caffeine) or decaffeinated group (150 mL decaffeinated coffee). We measured the changes in blood pressure (BP) and calculation speed upon coffee intake, stratifying with gene polymorphisms, e.g., those in adenosine A2A receptor (ADORA2A) and cytochrome P450 (CYP) 1A2, and daily caffeine consumption (≤90 mg/day and >90 mg/day). Overall, caffeine intake independently increased BP and calculation speed (p-values < 0.05), irrespective of the polymorphisms. In stratified analysis, a statistical significance within the caffeinated group was observed for the change in systolic BP in the stratum of CYP1A2 polymorphism with daily caffeine consumption ≤90 mg/day: change in systolic BP in the CYP1A2 rs762551 CC group (mean ± SD = 11.8 ± 5.9) was higher than that in the AA/CA group (4.1 ± 5.5). Gene polymorphisms may limitedly modify the effect of caffeine intake on hemodynamic parameters in combination with habitual caffeine consumption. KEYWORDS: ADORA2A; Blood pressure; CYP1A2; Caffeine; Polymorphism Dietary exposure to polychlorinated biphenyls and risk of heart failure - A population-based prospective cohort study. Åkesson A, Donat-Vargas C, Berglund M, Glynn A, Wolk A, Kippler M. Environ Int. 2019 Feb 15;126:1-6. doi: 10.1016/j.envint.2019.01.069. [Epub ahead of print] PMID: 30776745 Abstract BACKGROUND: Beneficial effects of fish consumption on heart failure (HF) may be modified by contaminants in fish. Polychlorinated biphenyls (PCBs) are of particular concern as they have been associated with well-established risk factors of HF, but current data are limited. OBJECTIVES: We aimed to assess the association between dietary PCB exposure and risk of HF, accounting for dietary intake of long-chain omega-3 fish fatty acids. DESIGN: We used the prospective population-based research structure SIMPLER (previously the Swedish Mammography Cohort and Cohort of Swedish Men) comprising 32,952 women and 36,546 men, free from cancer, cardiovascular disease and diabetes at baseline in 1997. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)] were obtained via a food frequency questionnaire at baseline. Incident cases of HF were ascertained through register linkage. RESULTS: During an average of 12 years of follow-up, we ascertained 2736 and 3128 incident cases of HF in women and men, respectively. In multivariable-adjusted models, mutually adjusted for PCBs and EPA-DHA, the relative risk (RR) for dietary PCB exposure was 1.48 (95% CI 1.12-1.96) in women and 1.42 (95% CI 1.08-1.86) in men, comparing extreme quintiles. Corresponding RRs for EPA-DHA intake were 0.71 (95% CI 0.54-0.93) and 0.82 (95% CI 0.63-1.07), respectively. CONCLUSIONS: Dietary exposure to PCBs was associated with an increased risk of HF in both women and men. EPA-DHA intake was associated with a lower risk of HF in women, with a similar tendency in men. KEYWORDS: Fish; Heart failure; Long-chain omega-3 fish fatty acids; Polychlorinated biphenyls Primary and secondary prevention of preterm birth: a review of systematic reviews and ongoing randomized controlled trials. Matei A, Saccone G, Vogel JP, Armson AB. Eur J Obstet Gynecol Reprod Biol. 2019 Jan 25. pii: S0301-2115(18)31153-9. doi: 10.1016/j.ejogrb.2018.12.022. [Epub ahead of print] Review. PMID: 30772047 Abstract BACKGROUND: Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interventions aimed at preventing PTB can be classified as primary, secondary, or tertiary prevention. OBJECTIVE: To conduct a review of systematic reviews on the effectiveness and safety of primary and secondary preterm birth prevention interventions. SEARCH STRATEGY: A systematic literature search of the Cochrane, PubMed/Medline, EMBASE and CINAHL databases was conducted on 2 September 2015, and updated on 21 November 2016. SELECTION CRITERIA: We included any published systematic review of randomized controlled trials (RCTs) or individual patient data (IPD) of RCTs related to primary or secondary prevention of PTB, published between 2005-2016 where gestational age at birth (of any interval) was a pre-specified outcome. Individual trials and non-systematic reviews were not eligible. DATA COLLECTION AND ANALYSIS: The population of interest was all pregnant women, regardless of PTB risk. The primary outcome was PTB < 37 weeks. MAIN RESULTS: In total, 112 reviews were included in this study. Overall there were 49 Cochrane and 63 non-Cochrane reviews. Eight were individual participant data (IPD) reviews. Sixty reviews assessed the effect of primary prevention interventions on risk of PTB. Positive effects were reported for lifestyle and behavioural changes (including diet and exercise); nutritional supplements (including calcium and zinc supplementation); nutritional education; screening for lower genital tract infections. Eighty-three systematic reviews were identified relating to secondary PTB prevention interventions. Positive effects were found for low dose aspirin among women at risk of preeclampsia; clindamycin for treatment of bacterial vaginosis; treatment of vaginal candidiasis; progesterone in women with prior spontaneous PTB and in those with short midtrimester cervical length; L-arginine in women at risk for preeclampsia; levothyroxine among women with tyroid disease; calcium supplementation in women at risk of hypertensive disorders; smoking cessation; cervical length screening in women with history of PTB with placement of cerclage in those with short cervix; cervical pessary in singleton gestations with short cervix; and treatment of periodontal disease. CONCLUSION: The overview serves as a guide to current evidence relevant to PTB prevention. Only a few interventions have been demononstrated to be effective, including cerclage, progesterone, low dose aspirin, and lifestyle and behavioural changes. For several of the interventions evaluated, there was insufficient evidence to assess whether they were effective or not. KEYWORDS: Neonatal; Obstetrics; Prematurity; Preterm birth; Prevention
  2. AlPater

    Al's CR updates

    HSF1/HSP pathway in the hippocampus is involved in SIRT1-mediated caloric restriction-induced neuroprotection after surgery in aged mice. Yao M, Zhao Z, Wei L, Zhou D, Xue Z, Ge S. Exp Gerontol. 2019 Feb 14. pii: S0531-5565(18)30537-0. doi: 10.1016/j.exger.2019.02.011. [Epub ahead of print] PMID: 30772489 Abstract Postoperative cognitive dysfunction is common in the elderly. Endoplasmic reticulum stress (ER-stress) increases neuronal apoptosis after surgery, and chaperone molecules, such as heat shock proteins (HSPs), help reduce unfolded protein reactions, thereby promoting protein homeostasis. Mammal sirtuin1 (SIRT1)-mediated deacetylation of heat shock factor 1 (HSF1) upregulates HSF1 binding to the HSP70 promoter. Caloric restriction (CR) improves cognition in many neurodegenerative models. In this study, we evaluated whether CR improves impaired learning and memory after surgery by attenuating ER-stress in an SIRT1-dependent manner. Male 18-month-old C57BL/6J mice receiving a 12-week CR or an ad libitum (AL) diet pre-intervention were challenged with tibial open fracture surgery and anesthesia or no treatment. We found a significant protective effect of CR on memory in contextual fear conditioning test after surgery compared with the AL group. CR alleviated ER-stress and neuronal apoptosis in the hippocampus induced by surgery. CR increased HSP70 expression through the HSF1/HSP pathway in a SIRT1-mediated manner, and inhibition of SIRT1 in the hippocampus by lentivirus injection partially reduced the benefits of CR (increased HSP70, deacetylated HSF1, reduced ER-stress, and improved memory). Taken together, our results showed that CR alleviates memory impairment postoperatively via attenuation of ER-stress in the hippocampus in an SIRT1-dependent manner, and the SIRT1/HSF1/HSP70 pathway is involved in this process. KEYWORDS: Caloric restriction; HSF1; HSP70; Neuroprotection; SIRT1 SAHMRI research reveals why high-protein diets are bad for you Clare Peddie, Science Reporter, The Advertiser February 14, 2019 https://www.adelaidenow.com.au/news/south-australia/sahmri-research-reveals-why-highprotein-diets-are-bad-for-you/news-story/9277b39a4ad84b5f1ce38b6ddfaf001f?nk=db94ec9b47b2d84b4dda8cee105fbb26-1550338206 >>>>>>>> Regulation of the Elongation Phase of Protein Synthesis Enhances Translation Accuracy and Modulates Lifespan. Xie J, de Souza Alves V, von der Haar T, O'Keefe L, Lenchine RV, Jensen KB, Liu R, Coldwell MJ, Wang X, Proud CG. Curr Biol. 2019 Feb 4. pii: S0960-9822(19)30031-4. doi: 10.1016/j.cub.2019.01.029. [Epub ahead of print] PMID: 30773367 https://www.cell.com/action/showPdf?pii=S0960-9822(19)30031-4 Xie et al. report that eukaryotic elongation factor 2 kinase (eEF2K), which impairs the rate of elongation, decreases misreading or termination readthrough errors and promotes the correct recognition of start codons in mRNAs. Depletion of the eEF2K ortholog or other factors implicated in translation fidelity in C. elegans decreases lifespan. Highlights •eEF2 kinase enhances the accuracy of protein synthesis under a range of conditions •mTORC1 inhibition improves translation accuracy by activating eEF2K •eEF2K assists correct start codon selection during translation initiation •Impairing translation fidelity reduces lifespan in C. elegans Summary Maintaining accuracy during protein synthesis is crucial to avoid producing misfolded and/or non-functional proteins. The target of rapamycin complex 1 (TORC1) pathway and the activity of the protein synthesis machinery are known to negatively regulate lifespan in many organisms, although the precise mechanisms involved remain unclear. Mammalian TORC1 signaling accelerates the elongation stage of protein synthesis by inactivating eukaryotic elongation factor 2 kinase (eEF2K), which, when active, phosphorylates and inhibits eEF2, which mediates the movement of ribosomes along mRNAs, thereby slowing down the rate of elongation. We show that eEF2K enhances the accuracy of protein synthesis under a range of conditions and in several cell types. For example, our data reveal it links mammalian (m)TORC1 signaling to the accuracy of translation. Activation of eEF2K decreases misreading or termination readthrough errors during elongation, whereas knocking down or knocking out eEF2K increases their frequency. eEF2K also promotes the correct recognition of start codons in mRNAs. Reduced translational fidelity is known to correlate with shorter lifespan. Consistent with this, deletion of the eEF2K ortholog or other factors implicated in translation fidelity in Caenorhabditis elegans decreases lifespan, and eEF2K is required for lifespan extension induced by nutrient restriction. Our data uncover a novel mechanism linking nutrient supply, mTORC1 signaling, and the elongation stage of protein synthesis, which enhances the accuracy of protein synthesis. Our data also indicate that modulating translation elongation and its fidelity affects lifespan. KEYWORDS: Caenorhabditis elegans; caloric restriction; eEF2; eEF2K; elongation; lifespan; mTOR; tRNA; translation fidelity ROLE of IGF-1 System in the Modulation of Longevity: Controversies and New Insights From a Centenarians' Perspective. Vitale G, Pellegrino G, Vollery M, Hofland LJ. Front Endocrinol (Lausanne). 2019 Feb 1;10:27. doi: 10.3389/fendo.2019.00027. eCollection 2019. Review. PMID: 30774624 https://www.frontiersin.org/articles/10.3389/fendo.2019.00027/full Abstract Human aging is currently defined as a physiological decline of biological functions in the body with a continual adaptation to internal and external damaging. The endocrine system plays a major role in orchestrating cellular interactions, metabolism, growth, and aging. Several in vivo studies from worms to mice showed that downregulated activity of the GH/IGF-1/insulin pathway could be beneficial for the extension of human life span, whereas results are contradictory in humans. In the present review, we discuss the potential role of the IGF-1 system in modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better physiologic reserve capacity, a shift of cellular metabolism from cell proliferation to repair activities and a decrease in accumulation of senescent cells. Therefore, understanding of the link between IGF-1/insulin system and longevity may have future clinical applications in promoting healthy aging and in Rehabilitation Medicine. KEYWORDS: IGF-1; aging; caloric restriction; centenarians; insulin; longevity; rehabilitation medicine
  3. Influence of Eating Schedule on the Postprandial Response: Gender Differences. Masihy M, Monrroy H, Borghi G, Pribic T, Galan C, Nieto A, Accarino A, Azpiroz F. Nutrients. 2019 Feb 14;11(2). pii: E401. doi: 10.3390/nu11020401. PMID: 30769861 https://www.mdpi.com/2072-6643/11/2/401/htm Abstract Ingestion of a meal induces conscious sensations depending of the characteristics of the meal and the predisposition of the eater. We hypothesized that the eating schedule plays a conditioning role, specifically, that an extemporaneous meal is less rewarding than when eaten at the habitual schedule. We conducted a randomized parallel trial in 10 women and 10 men comparing the responses to a consistent savoury lunch-type meal (stewed beans) eaten at the habitual afternoon schedule or at an unconventional time in the morning. Schedule and gender differences were analyzed by repeated measures analysis of covariance. In women, the sensory experience induced by the probe meal, particularly postprandial satisfaction, was weaker when eaten at an unconventional time for breakfast. Men were resilient to the schedule effect and experienced the same sensations regardless of the timing of ingestion; the effect of the eating schedule was significantly more pronounced in women for fullness (F(1,55) = 14.9; p < 0.001), digestive well-being (F(1,36.8) = 22.3; p < 0.001), mood (F(1,12.4) = 13.8; p < 0.001), and anxiety (F(1,11.9) = 10.9; p = 0.001). No differences in the physiological responses induced by the afternoon and morning meals were detected either in women or men. Our data indicate that women are more susceptible to changes in meal schedule than men. KEYWORDS: eating habits; gender differences; hedonic response; homeostatic responses; meal ingestion; meal schedule; postprandial sensations Searching Tardigrades for Lifesaving Secrets Researchers are drawing inspiration from the proteins that they think let hearty water bears cheat time by decelerating their biology. Tardigrades have special proteins that scientists believe help them achieve suspended animation. By Steph Yin Feb. 15, 2019 https://www.nytimes.com/2019/02/15/health/tardigrades-suspended-animation.html
  4. The exceptional longevity of the naked mole-rat may be explained by mitochondrial antioxidant defenses. Munro D, Baldy C, Pamenter ME, Treberg JR. Aging Cell. 2019 Feb 15:e12916. doi: 10.1111/acel.12916. [Epub ahead of print] PMID: 30768748 Abstract Naked mole-rats (NMRs) are mouse-sized mammals that exhibit an exceptionally long lifespan (>30 vs. <4 years for mice), and resist aging-related pathologies such as cardiovascular and pulmonary diseases, cancer, and neurodegeneration. However, the mechanisms underlying this exceptional longevity and disease resistance remain poorly understood. The oxidative stress theory of aging posits that (a) senescence results from the accumulation of oxidative damage inflicted by reactive oxygen species (ROS) of mitochondrial origin, and (b) mitochondria of long-lived species produce less ROS than do mitochondria of short-lived species. However, comparative studies over the past 28 years have produced equivocal results supporting this latter prediction. We hypothesized that, rather than differences in ROS generation, the capacity of mitochondria to consume ROS might distinguish long-lived species from short-lived species. To test this hypothesis, we compared mitochondrial production and consumption of hydrogen peroxide (H2 O2 ; as a proxy of overall ROS metabolism) between NMR and mouse skeletal muscle and heart. We found that the two species had comparable rates of mitochondrial H2 O2 generation in both tissues; however, the capacity of mitochondria to consume ROS was markedly greater in NMRs. Specifically, maximal observed consumption rates were approximately two and fivefold greater in NMRs than in mice, for skeletal muscle and heart, respectively. Our results indicate that differences in matrix ROS detoxification capacity between species may contribute to their divergence in lifespan. KEYWORDS: Heterocephalus glaber ; antioxidants; mitochondria; reactive oxygen species; skeletal muscle heart
  5. AlPater

    Al's CR updates

    FEBRUARY 14, 2019 Uncovering a 'smoking gun' of biological aging clocks by Harvard T.H. Chan School of Public Health https://medicalxpress.com/news/2019-02-uncovering-gun-biological-aging-clocks.html >>>>>>>>>>>>>>>> Ribosomal DNA harbors an evolutionarily conserved clock of biological aging. Wang M, Lemos B. Genome Res. 2019 Feb 14. doi: 10.1101/gr.241745.118. [Epub ahead of print] PMID: 30765617 https://sci-hub.tw/10.1101/gr.241745.118 Abstract The ribosomal DNA (rDNA) is the most evolutionarily conserved segment of the genome and gives origin to the nucleolus, an energy intensive nuclear organelle and major hub influencing myriad molecular processes from cellular metabolism to epigenetic states of the genome. The rDNA/nucleolus has been directly and mechanistically implicated in aging and longevity in organisms as diverse as yeasts, Drosophila, and humans. The rDNA is also a significant target of DNA methylation that silences supernumerary rDNA units and regulates nucleolar activity. Here, we introduce an age clock built exclusively with CpG methylation within the rDNA. The ribosomal clock is sufficient to accurately estimate individual age within species, is responsive to genetic and environmental interventions that modulate life-span, and operates across species as distant as humans, mice, and dogs. Further analyses revealed a significant excess of age-associated hypermethylation in the rDNA relative to other segments of the genome, and which forms the basis of the rDNA clock. Our observations identified an evolutionarily conserved marker of aging that is easily ascertained, grounded on nucleolar biology, and could serve as a universal marker to gauge individual age and response to interventions in humans as well as laboratory and wild organisms across a wide diversity of species. [Calorie restriction (CR) has long been reported to extend lifespan and retard aging. For the C57BL/6 mice subjected to CR starting at 14 wk old, we observed lower rDNAm age compared to their ad libitum (AL) controls (one-tailed t-test of the differences between rDNAm age and chronological age, P = 1.17 × 10−9) (Fig. 3A). The CR effect remained obvious when instead examining the B6D2F1 strain mice (P = 0.002) (Supplemental Fig. S7A).]
  6. AlPater

    Al's CR updates

    The association between dietary protein intake, energy intake and physical frailty- results from the Rotterdam Study. Schoufour JD, Franco OH, Kiefte-de Jong JC, Trajanoska K, Stricker B, Brusselle G, Rivadeneira F, Lahousse L, Voortman T. Br J Nutr. 2018 Nov 13:1-23. doi: 10.1017/S0007114518003367. [Epub ahead of print] No abstract available. PMID: 30419973 https://sci-hub.tw/10.1017/S0007114518003367 Interaction of growth hormone and calorie restriction. Masternak MM, Bartke A. Expert Rev Endocrinol Metab. 2006 Nov;1(6):775-781. doi: 10.1586/17446651.1.6.775. PMID: 30754151 https://sci-hub.tw/https://www.tandfonline.com/doi/full/10.1586/17446651.1.6.775 Abstract Sustaining health and extending longevity have been perpetual goals of all human societies. For almost as long, there has been an ongoing effort to develop treatments that could prevent aging and, more importantly, make us live longer and more healthily. At present, there is one known intervention that delays aging, increases lifespan and prevents diseases in many animal species: calorie restriction. There are other physiological factors that are believed to have corresponding impacts on longevity and aging, including growth hormone and the insulin/insulin-like growth factor 1 signaling pathway. However, there is still much debate regarding the complex action of growth hormone on lifespan and aging. KEYWORDS: Ames dwarf; GHR-KO; calorie restriction; growth hormone; growth hormone receptor; knockout; longevity
  7. Conjugated Linoleic Acid Effects on Cancer, Obesity, and Atherosclerosis: A Review of Pre-Clinical and Human Trials with Current Perspectives. den Hartigh LJ. Nutrients. 2019 Feb 11;11(2). pii: E370. doi: 10.3390/nu11020370. Review. PMID: 30754681 [pdf availed from https://www.mdpi.com/2072-6643/11/2/370 site.] Abstract Obesity and its comorbidities, including type 2 diabetes and cardiovascular disease, are straining our healthcare system, necessitating the development of novel strategies for weight loss. Lifestyle modifications, such as exercise and caloric restriction, have proven effective against obesity in the short term, yet obesity persists because of the high predilection for weight regain. Therefore, alternative approaches to achieve long term sustainable weight loss are urgently needed. Conjugated linoleic acid (CLA), a fatty acid found naturally in ruminant animal food products, has been identified as a potential anti-obesogenic agent, with substantial efficacy in mice, and modest efficacy in obese human populations. Originally described as an anti-carcinogenic fatty acid, in addition to its anti-obesogenic effects, CLA has now been shown to possess anti-atherosclerotic properties. This review summarizes the pre-clinical and human studies conducted using CLA to date, which collectively suggest that CLA has efficacy against cancer, obesity, and atherosclerosis. In addition, the potential mechanisms for the many integrative physiological effects of CLA supplementation will be discussed in detail, including an introduction to the gut microbiota as a potential mediator of CLA effects on obesity and atherosclerosis. KEYWORDS: atherosclerosis; cancer; conjugated linoleic acid (CLA); diabetes; gut microbiota; obesity The Role of the Microbiome in Cancer Initiation and Progression: How Microbes and Cancer Cells Utilize Excess Energy and Promote One Another's Growth. Whisner Curr Nutr Rep. 2019 Feb 13. doi: 10.1007/s13668-019-0257-2. [Epub ahead of print] Review. PMID: 30758778 https://sci-hub.tw/10.1007/s13668-019-0257-2 Abstract PURPOSE OF REVIEW: We use an ecological lens to understand how microbes and cancer cells coevolve inside the ecosystems of our bodies. We describe how microbe-cancer cell interactions contribute to cancer progression, including cooperation between microbes and cancer cells. We discuss the role of the immune system in preventing this apparent 'collusion' and describe how microbe-cancer cell interactions lead to opportunities and challenges in treating cancer. RECENT FINDINGS: Microbiota influence many aspects of our health including our cancer risk. Since both microbes and cancer cells rely on incoming resources for their survival and replication, excess energy and nutrient input from the host can play a role in cancer initiation and progression. Certain microbes enhance cancer cell fitness by promoting proliferation and protecting cancer cells from the immune system. How diet influences these interactions remains largely unknown but recent evidence suggests a role for nutrients across the cancer continuum. KEYWORDS: Caloric restriction; Cancer; Cell proliferation; Diet; Ecology; Immune system; Inflammation; Metastasis; Microbe; Microbiome; Microbiota; Neoplasms; Neoplastic processes; Nutrition; Western diet Meals with Similar Fat Content from Different Dairy Products Induce Different Postprandial Triglyceride Responses in Healthy Adults: A Randomized Controlled Cross-Over Trial. Hansson P, Holven KB, Øyri LKL, Brekke HK, Biong AS, Gjevestad GO, Raza GS, Herzig KH, Thoresen M, Ulven SM. J Nutr. 2019 Feb 13. doi: 10.1093/jn/nxy291. [Epub ahead of print] PMID: 30759235 https://sci-hub.tw/10.1093/jn/nxy291 Abstract BACKGROUND: Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations. OBJECTIVE: We investigated the effect of meals with similar amounts of fat from different dairy products on postprandial TG concentrations over 6 h in healthy adults. METHODS: A randomized controlled cross-over study was performed on 47 subjects (30% men), with median (25th-75th percentile) age of 32 (25-46) y and body mass index of 23.6 (21.0-25.8) kg/m2. Meals included 1 of butter, cheese, whipped cream, or sour cream, corresponding to 45 g of fat (approximately 60 energy%). Serum concentrations of TGs (primary outcome), and total cholesterol (TC), low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), insulin, glucose, non-esterified fatty acids, and plasma glucose-dependent insulinotropic polypeptide (secondary outcomes) were measured before the meal and 2, 4, and 6 h postprandially. Incremental AUC (iAUC) was calculated for the responses, and data were analyzed using a linear mixed model. RESULTS: Sour cream induced a 61% larger TG-iAUC0-6 h compared to whipped cream (P < 0.001), a 53% larger TG-iAUC0-6 h compared to butter (P < 0.001), and a 23% larger TG-iAUC0-6 h compared to cheese (P = 0.05). No differences in TG-iAUC0-6 h between the other meals were observed. Intake of sour cream induced a larger HDL cholesterol-iAUC0-6 h compared to cheese (P = 0.01). Intake of cheese induced a 124% larger insulin iAUC0-6 h compared to butter (P = 0.006). No other meal effects were observed. CONCLUSIONS: High-fat meals containing similar amount of fat from different dairy products induce different postprandial effects on serum TGs, HDL cholesterol, and insulin in healthy adults. The potential mechanisms and clinical impact of our findings remain to be further elucidated. Dietary total antioxidant capacity and mortality from all causes, cardiovascular disease and cancer: a systematic review and dose-response meta-analysis of prospective cohort studies. Parohan M, Anjom-Shoae J, Nasiri M, Khodadost M, Khatibi SR, Sadeghi O. Eur J Nutr. 2019 Feb 11. doi: 10.1007/s00394-019-01922-9. [Epub ahead of print] Review. PMID: 30756144 Abstract PURPOSE: No conclusive information is available about the association between dietary total antioxidant capacity (DTAC) and risk of mortality. Current meta-analysis of prospective cohort studies was done to summarize available findings on the association between DTAC and risk of death from all-cause, cancer and cardiovascular diseases (CVDs). METHODS: Online databases were searched to detect relevant publications up to January 2018, using relevant keywords. To pool data, either fixed-effects or random-effects model was used. Furthermore, linear and non-linear dose-response analyses were also done. RESULTS: In total, five prospective studies were included in the current systematic review and meta-analysis. In a follow-up period of 4.3-16.5 years, there were 38,449 deaths from all-cause, 4470 from cancer and 2841 from CVDs among 226,297 individuals. A significant inverse association was found between DTAC and all-cause mortality (combined effect size: 0.62, 95% CI 0.60-0.64). Such finding was also seen for cancer (combined effect size: 0.81, 95% CI 0.75-0.88) and CVD (combined effect size: 0.71, 95% CI 0.63-0.82) mortality. Findings from linear dose-response meta-analysis revealed that a 5 mmol/day increment in DTAC based on ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) was associated with 7% and 15% lower risk of all-cause mortality, respectively. Based on findings from non-linear dose-response meta-analysis, a significant reduction in risk of all-cause mortality was seen when increasing FRAP from 2 to 12 mmol/day (P-nonlinearity = 0.002) and ORAC from 5 to 11 mmol/day (P-nonlinearity < 0.001). CONCLUSIONS: Adherence to diet with high total antioxidant capacity was associated with decreased risk of death from all-cause, cancer and CVDs. KEYWORDS: Antioxidants; Cancer; Cardiovascular; Dose–response; Meta-analysis; Mortality Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh. Bozack AK, Hall MN, Liu X, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Am J Clin Nutr. 2019 Feb 1;109(2):380-391. doi: 10.1093/ajcn/nqy148. PMID: 30590411 Abstract BACKGROUND: Arsenic exposure through drinking water persists in many regions. Inorganic As (InAs) is methylated to monomethyl-arsenical species (MMAs) and dimethyl-arsenical species (DMAs), facilitating urinary excretion. Arsenic methylation is dependent on one-carbon metabolism, which is influenced by nutritional factors such as folate and creatine. OBJECTIVE: This study investigated the effects of folic acid (FA) and/or creatine supplementation on the proportion of As metabolites in urine. DESIGN: In a 24-wk randomized, double-blinded, placebo-controlled trial, 622 participants were assigned to receive FA (400 or 800 μg per day), 3 g creatine per day, 400 μg FA + 3 g creatine per day, or placebo. The majority of participants were folate sufficient; all received As-removal water filters. From wk 12-24, half of the participants receiving FA received placebo. RESULTS: Among groups receiving FA, the mean decrease in ln(%InAs) and %MMAs and increase in %DMAs exceeded those of the placebo group at wk 6 and 12 (P < 0.05). In the creatine group, the mean decrease in %MMAs exceeded that of the placebo group at wk 6 and 12 (P < 0.05); creatine supplementation did not affect change in %InAs or %DMAs. The decrease in %MMAs at wk 6 and 12 was larger in the 800 µg FA than in the 400 µg FA group (P = 0.034). There were no differences in treatment effects between the 400 µg FA and creatine + FA groups. Data suggest a rebound in As metabolite proportions after FA cessation; at wk 24, log(%InAs) and %DMAs were not significantly different than baseline levels among participants who discontinued FA supplementation. CONCLUSIONS: The results of this study confirm that FA supplementation rapidly and significantly increases methylation of InAs to DMAs. Further research is needed to understand the strong cross-sectional associations between urinary creatinine and As methylation in previous studies. The effect of nuts on markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials. Tindall AM, Johnston EA, Kris-Etherton PM, Petersen KS. Am J Clin Nutr. 2019 Feb 1;109(2):297-314. doi: 10.1093/ajcn/nqy236. PMID: 30722007 Abstract BACKGROUND: Observational evidence suggests higher nut consumption is associated with better glycemic control; however, it is unclear if this association is causal. OBJECTIVES: We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effect of tree nuts and peanuts on markers of glycemic control in adults. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted. A total of 1063 potentially eligible articles were screened in duplicate. From these articles, 40 were eligible for inclusion and data from these articles were extracted in duplicate. The weighted mean difference (WMD) between the nut intervention and control arms was determined for fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) using the DerSimonian and Laird random-effects method. For outcomes where a limited number of studies were published, a qualitative synthesis was presented. RESULTS: A total of 40 randomized controlled trials including 2832 unique participants, with a median duration of 3 mo (range: 1-12 mo), were included. Overall consumption of tree nuts or peanuts had a favorable effect on HOMA-IR (WMD: -0.23; 95% CI: -0.40, -0.06; I2 = 51.7%) and fasting insulin (WMD: -0.40 μIU/mL; 95% CI: -0.73, -0.07 μIU/mL; I2 = 49.4%). There was no significant effect of nut consumption on fasting blood glucose (WMD: -0.52 mg/dL; 95% CI: -1.43, 0.38 mg/dL; I2 = 53.4%) or HbA1c (WMD: 0.02%; 95% CI: -0.01%, 0.04%; I2 = 51.0%). CONCLUSIONS: Consumption of peanuts or tree nuts significantly decreased HOMA-IR and fasting insulin; there was no effect of nut consumption on HbA1c or fasting glucose. The results suggest that nut consumption may improve insulin sensitivity. In the future, well-designed clinical trials are required to elucidate the mechanisms that account for these observed effects.
  8. AlPater

    Al's CR updates

    Diets consisting of fewer calories improve cell performance Date: February 12, 2019 Source: Fundação de Amparo à Pesquisa do Estado de São Paulo Summary: Animal experiments have shown that caloric restriction causes cellular changes that can prevent diseases. https://www.sciencedaily.com/releases/2019/02/190212120125.htm
  9. Redox parameters as markers of the rate of aging and predictors of lifespan. Martínez de Toda I, Vida C, Garrido A, De la Fuente M. J Gerontol A Biol Sci Med Sci. 2019 Feb 11. doi: 10.1093/gerona/glz033. [Epub ahead of print] PMID: 30753310 Abstract Oxidative stress has been reported to increase with aging and although several age-related changes in redox parameters have been described, none of them have been verified as markers of the rate of aging and lifespan. Therefore, antioxidant (catalase, glutathione peroxidase and reductase activities and reduced glutathione) and oxidant (oxidized glutathione, basal superoxide anion and malondialdehyde concentrations) parameters were studied in whole blood cells from humans divided into different age groups (adult, mature, elderly, nonagenarian and centenarian) in a cross-sectional study. Moreover, the same parameters were investigated in peritoneal leukocytes of mice at the analogous human ages (adult, mature, old, very old and long-lived) in a longitudinal study as well as in adult prematurely aging mice (PAM). The results reveal that the age-related alterations of these markers are similar in humans and mice, with decreased antioxidants and increased oxidants in old subjects whereas long-lived individuals show similar values to those in adults. Additionally, adult PAM showed similar values to those in chronologically old mice and had a shorter lifespan than non-prematurely aging mice. Thus, these parameters could be proposed as markers of the rate of aging and used to ascertain biological age in humans.
  10. AlPater

    Al's CR updates

    Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction. Rickert E, Fernandez MO, Choi I, Gorman M, Olefsky JM, Webster NJG. J Endocr Soc. 2018 Dec 24;3(2):427-445. doi: 10.1210/js.2018-00318. eCollection 2019 Feb 1. PMID: 30746504 https://watermark.silverchair.com/js.2018-00318.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAkIwggI-BgkqhkiG9w0BBwagggIvMIICKwIBADCCAiQGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM9UXXP1GwNo5vVZJDAgEQgIIB9d8qx_eK1fyqdKdCDW0lUpsftxiWGL0qUsGMWiGPQHaZpzS3H9IBIM63-T-mF1mm4_nRzAQ73u3F6zXhC8GR8W0zkmDwIFcmwjrn7e7ROboSiskPGViNzmC7KGvKCmfuOfIUZx57cjnK0F0uqZD23z5SE7eB2TB7JAGK0pjEHU7Xuq18SSt_X1aC80j-YLGnsFr2y_ybiGu3Wevh5_VdlmZYenpWr6-86sPjtuoxX3UebbHernlD7hkBEbLjeFgLw_YWNWBePNr6mXZKMS5q6nggm-nFctqB09T8SdYOvA597aykG-VW4zLG3BF3tWs55V2U0NuV5lxLxSx2_mFrhnDN82N7IJ-4TROAEulRRl3S423OabHiUNJzq9NKMAsyJiW9mV_6z5lolpB3OgVYlcD2h1SFxM6SgoiiUOYTxXHQDySMZSea2DEB-vPSZXxX7_DNW5R-BsRrH1PttKiFmHMlpeEH1z0FuGobgQ-KtOEEJRYS8k2WG62hfEmCe-7D6bcORJ8ys82VxS7hVpCaPOx3YC4q3Qrl2FHfETX1pFedbthme65udK1vMKweGA0jlW7_7mQjS1fyTxzfItfYEhksmKqbPW4ezLLJcyWPyE9OVbGuArUyxGdZ-CoZFuLzKtLFzMyqiyKdx4aygSODy3dm6KjcXg Abstract Sirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (N-MUT) or wild-type (WT) SIRT1 (N-OX) in mature neurons. N-OX male and female mice had impaired glucose tolerance, and N-MUT female, but not male, mice had improved glucose tolerance compared with that of WT littermates. Furthermore, glucose tolerance was improved in all mice with caloric restriction (CR) but was greater in the N-OX mice, who had better glucose tolerance than their littermates. At the reproductive level, N-OX females had impaired estrous cycles, with increased cycle length and more time in estrus. LH and progesterone surges were absent on the evening of proestrus in the N-OX mice, suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology revealing fewer corpora lutea. Despite this defect, the mice were still fertile when mated to WT mice on the day of proestrus, indicating that the mice could respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms. KEYWORDS: caloric restriction; fertility; glucose intolerance; neurons
  11. Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial. Harvey CJDC, Schofield GM, Zinn C, Thornley SJ, Crofts C, Merien FLR. PeerJ. 2019 Feb 5;7:e6273. doi: 10.7717/peerj.6273. eCollection 2019. PMID: 30740270 https://peerj.com/articles/6273/ Abstract BACKGROUND: Low-carbohydrate, high-fat (LCHF) diets are useful for treating a range of health conditions, but there is little research evaluating the degree of carbohydrate restriction on outcome measures. This study compares anthropometric and cardiometabolic outcomes between differing carbohydrate-restricted diets. OBJECTIVE: Our hypothesis was that moderate carbohydrate restriction is easier to maintain and more effective for improving cardiometabolic health markers than greater restriction. DESIGN: A total of 77 healthy participants were randomised to a very low-carbohydrate ketogenic diet (VLCKD), low-carbohydrate diet (LCD), or moderate-low carbohydrate diet (MCD), containing 5%, 15% and 25% total energy from carbohydrate, respectively, for 12-weeks. Anthropometric and metabolic health measures were taken at baseline and at 12 weeks. Using ANOVA, both within and between-group outcomes were analysed. RESULTS: Of 77 participants, 39 (51%) completed the study. In these completers overall, significant reductions in weight and body mass index occurred ((mean change) 3.7 kg/m2; 95% confidence limits (CL): 3.8, 1.8), along with increases in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, (0.49 mmol/L; 95% CL; 0.06, 0.92; p = 0.03), and total cholesterol concentrations (0.11 mmol/L; 95% CL; 0.00, 0.23; p = 0.05). Triglyceride (TG) levels were reduced by 0.12 mmol/L (95% CL; -0.20, 0.02; p = 0.02). No significant changes occurred between groups. The largest improvements in high density lipoprotein cholesterol (HDL-c) and TG and anthropometric changes occurred for the VLCKD group. CONCLUSIONS: Low-carbohydrate, high-fat diets have a positive effect on markers of health. Adherence to the allocation of carbohydrate was more easily achieved in MCD, and LCD groups compared to VLCKD and there were comparable improvements in weight loss and waist circumference and greater improvements in HDL-c and TG with greater carbohydrate restriction. KEYWORDS: Adherence; Carbohydrate restriction; Cardiometabolic health; Diet; Ketogenic; LCHF; Low-carbohydrate; Nutrition Associations of specific dietary protein with longitudinal insulin resistance, prediabetes and type 2 diabetes: The Rotterdam Study. Chen Z, Franco OH, Lamballais S, Ikram MA, Schoufour JD, Muka T, Voortman T. Clin Nutr. 2019 Jan 31. pii: S0261-5614(19)30040-8. doi: 10.1016/j.clnu.2019.01.021. [Epub ahead of print] PMID: 30739809 https://sci-hub.tw/10.1016/j.clnu.2019.01.021 Abstract BACKGROUND & AIMS: High protein intake has been linked to increased type 2 diabetes (T2D) risk. However, if this association differs by protein from specific food sources, and if a habitual high protein intake affects insulin resistance and prediabetes risk are largely unknown. We aimed to investigate associations between protein intake from different food sources with longitudinal insulin resistance, and risk of prediabetes and T2D. METHODS: Our analyses included 6822 participants aged ≥45 years without diabetes at baseline in three sub-cohorts of the prospective population-based Rotterdam Study. We measured protein intake at baseline using food-frequency questionnaires. Data on longitudinal homeostatic model assessment of insulin resistance (HOMA-IR), and incidence of prediabetes and T2D were available from 1993 to 2014. RESULTS: During follow-up, we documented 931 prediabetes cases and 643 T2D cases. After adjusting for sociodemographic, lifestyle, and dietary factors, higher total protein intake was associated with higher longitudinal HOMA-IR and with higher risk of prediabetes and T2D (per 5% increment in energy from protein at the expense of carbohydrate, for HOMA-IR: β = 0.10, (95%CI 0.07, 0.12); for prediabetes: HR = 1.34 (1.24 1.44); for T2D: HR = 1.37 (1.26, 1.49)). These associations were mainly driven by total animal protein (for HOMA-IR: 0.10 (0.07, 0.12); for prediabetes: 1.35 (1.24, 1.45); for T2D: 1.37 (1.26; 1.49)). The harmful associations of total animal protein were contributed to by protein from meat, fish, and dairy (e.g. for HOMA-IR: protein from meat, 0.13 (0.10, 0.17); from fish, 0.08 (0.03, 0.13); from dairy, 0.04 (0.0003, 0.08)). After additional adjustment for longitudinal waist circumference, associations of total protein and total animal protein with longitudinal HOMA-IR and prediabetes risk were attenuated, but remained statistically significant. Total plant protein, as well as protein from legumes and nuts, from grains, from potatoes, or from fruits and vegetables, was not associated with any of the outcomes. CONCLUSIONS: Higher intake of animal protein, from meat, dairy and fish food sources, is associated with higher longitudinal insulin resistance and risk of prediabetes and T2D, which may be partly mediated by obesity over time. Furthermore, plant protein from different sources is not related to insulin resistance, and risk of prediabetes and T2D. Our findings highlight the importance of specific protein food sources and that habitual high animal protein intake may already in early stages be harmful in the development of T2D. KEYWORDS: Animal protein intake; Insulin resistance; Plant protein intake; Prediabetes; Protein intake; Type 2 diabetes Stage 1 hypertension, but not elevated blood pressure, predicts 10-year fatal and non-fatal CVD events in healthy adults: the ATTICA Study. Critselis E, Chrysohoou C, Kollia N, Georgousopoulou EN, Tousoulis D, Pitsavos C, Panagiotakos DB; ATTICA Study group. J Hum Hypertens. 2019 Feb 11. doi: 10.1038/s41371-019-0169-z. [Epub ahead of print] PMID: 30742050 https://sci-hub.tw/10.1038/s41371-019-0169-z Abstract The study evaluated the extent to which high normal blood pressure (HNBP), elevated BP, and Stage 1 hypertension predict 10-year incidence of cardiovascular disease (CVD). A population-based, prospective cohort study was conducted among 3042 randomly selected Greek adults, aged 18-89 years. Following 10-years follow-up (2002-2012), incidence of non-fatal and fatal CVD (ICD-10) was achieved in 2020 participants. The analytic sample (n = 1403) excluded hypertensive patients. At baseline, the prevalence rate of HNBP, elevated BP, and Stage 1 hypertension was 44.6% (n = 626), 29.0% (n = 408), and 15.5% (n = 218), respectively. During follow-up, the 10-year combined (fatal or non-fatal) CVD incidence rates in HNBP, elevated BP, and Stage 1 hypertensive individuals were 15.6% (n = 98), 12.0% (n = 49), and 22.5% (n = 49), respectively, as compared to 6.3% (n = 49) in normotensives (all p's < 0.0001). As compared to normotensives (and following the adjustment for known demographic, lifestyle and clinical confounding factors), HNBP participants had a 1.5-fold (Adjusted Hazard Ratio, Adj. HR: 1.49; 95% CI: 1.00-2.20) increased risk of 10-year CVD events. Similarly, Stage 1 hypertensive participants had an approximately twofold (Adj. HR: 1.90; 95% CI: 1.16-3.08) increased risk for 10-year CVD, particularly among males (Adj. HR: 2.03; 95% CI: 1.08-3.83). However, individuals with elevated BP did not exhibit a differential risk for developing 10-year CVD events (Adj. HR: 1.28; 95% CI: 0.82-2.02). Therefore, since HNBP and Stage 1 hypertension individuals exhibit a notable increased risk of 10-year fatal and non-fatal CVD, the implementation of targeted primary and secondary prevention interventions may deter both CVD and related adverse health outcomes. Association Between Ultraprocessed Food Consumption and Risk of Mortality Among Middle-aged Adults in France. Schnabel L, Kesse-Guyot E, Allès B, Touvier M, Srour B, Hercberg S, Buscail C, Julia C. JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7289. [Epub ahead of print] PMID: 30742202 https://sci-hub.tw/10.1001/jamainternmed.2018.7289 Abstract IMPORTANCE: Growing evidence indicates that higher intake of ultraprocessed foods is associated with higher incidence of noncommunicable diseases. However, to date, the association between ultraprocessed foods consumption and mortality risk has never been investigated. OBJECTIVE: To assess the association between ultraprocessed foods consumption and all-cause mortality risk. DESIGN, SETTING, AND PARTICIPANTS: This observational prospective cohort study selected adults, 45 years or older, from the French NutriNet-Santé Study, an ongoing cohort study that launched on May 11, 2009, and performed a follow-up through December 15, 2017 (a median of 7.1 years). Participants were selected if they completed at least 1 set of 3 web-based 24-hour dietary records during their first 2 years of follow-up. Self-reported data were collected at baseline, including sociodemographic, lifestyle, physical activity, weight and height, and anthropometrics. EXPOSURES: The ultraprocessed foods group (from the NOVA food classification system), characterized as ready-to-eat or -heat formulations made mostly from ingredients usually combined with additives. Proportion (in weight) of ultraprocessed foods in the diet was computed for each participant. MAIN OUTCOMES AND MEASURES: The association between proportion of ultraprocessed foods and overall mortality was the main outcome. Mean dietary intakes from all of the 24-hour dietary records available during the first 2 years of follow-up were calculated and considered as the baseline usual food-and-drink intakes. Mortality was assessed using CépiDC, the French national registry of specific mortality causes. Hazard ratios (HRs) and 95% CIs were determined for all-cause mortality, using multivariable Cox proportional hazards regression models, with age as the underlying time metric. RESULTS: A total of 44 551 participants were included, of whom 32 549 (73.1%) were women, with a mean (SD) age at baseline of 56.7 (7.5) years. Ultraprocessed foods accounted for a mean (SD) proportion of 14.4% (7.6%) of the weight of total food consumed, corresponding to a mean (SD) proportion of 29.1% (10.9%) of total energy intake. Ultraprocessed foods consumption was associated with younger age (45-64 years, mean [SE] proportion of food in weight, 14.50% [0.04%]; P < .001), lower income (<€1200/mo, 15.58% [0.11%]; P < .001), lower educational level (no diploma or primary school, 15.50% [0.16%]; P < .001), living alone (15.02% [0.07%]; P < .001), higher body mass index (calculated as weight in kilograms divided by height in meters squared; ≥30, 15.98% [0.11%]; P < .001), and lower physical activity level (15.56% [0.08%]; P < .001). A total of 602 deaths (1.4%) occurred during follow-up. After adjustment for a range of confounding factors, an increase in the proportion of ultraprocessed foods consumed was associated with a higher risk of all-cause mortality (HR per 10% increment, 1.14; 95% CI, 1.04-1.27; P = .008). CONCLUSIONS AND RELEVANCE: An increase in ultraprocessed foods consumption appears to be associated with an overall higher mortality risk among this adult population; further prospective studies are needed to confirm these findings and to disentangle the various mechanisms by which ultraprocessed foods may affect health. Fitness and Body Mass Index During Adolescence and Disability Later in Life: A Cohort Study. Henriksson P, Henriksson H, Tynelius P, Berglind D, Löf M, Lee IM, Shiroma EJ, Ortega FB. Ann Intern Med. 2019 Feb 12. doi: 10.7326/M18-1861. [Epub ahead of print] PMID: 30743265 Abstract BACKGROUND: Low physical fitness, obesity, and the combination of the two in adolescence may be related to risk for disability in adulthood, but this has rarely been studied. OBJECTIVE: To examine individual and combined associations of cardiorespiratory fitness and obesity in male adolescents with later receipt of a disability pension due to all and specific causes. DESIGN: Population-based cohort study. SETTING: Sweden. PARTICIPANTS: 1 079 128 Swedish adolescents aged 16 to 19 years who were conscripted into the military between 1972 and 1994. MEASUREMENTS: Cardiorespiratory fitness and body mass index (BMI) were measured at conscription and were related to information on later receipt of a disability pension obtained from the Social Insurance Agency. RESULTS: Over a median follow-up of 28.3 years, 54 304 men were granted a disability pension. Low cardiorespiratory fitness was strongly associated with later receipt of a disability pension due to all causes (hazard ratio, 3.74 [95% CI, 3.55 to 3.95] for lowest vs. highest fitness decile) and specific causes (psychiatric, musculoskeletal, injuries, nervous system, circulatory, and tumors). Obesity was associated with greater risk for receipt of a disability pension due to all and specific causes, with the greatest risks observed for class II and III obesity. Compared with being unfit, being moderately or highly fit was associated with attenuated risk for receipt of a disability pension across BMI categories. LIMITATION: The cohort did not include women, had data on smoking and alcohol intake only in a subsample, and lacked repeated measures of exposures and covariates. CONCLUSION: Low cardiorespiratory fitness, obesity, and the combination of the two were strongly associated with later chronic disability due to a wide range of diseases and causes. Although additional well-designed studies are required, these findings support the importance of high cardiorespiratory fitness and healthy body weight during adolescence to prevent later chronic disease.
  12. AlPater

    Al's CR updates

    Changing how we age February 10, 2019 By Peter McDermott https://www.irishecho.com/2019/02/changing-how-we-age
  13. It might give you a huge laxative effect, but: https://en.wikibooks.org/wiki/Fundamentals_of_Human_Nutrition/Glycerol_and_fatty_acids#12.3_Glycerol_and_Fatty_Acids
  14. Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared to eicosapentaenoic acid in healthy men and women. Lee JB, Notay K, Klingel S, Chabowski A, Mutch DM, Millar PJ. Am J Physiol Heart Circ Physiol. 2019 Feb 8. doi: 10.1152/ajpheart.00677.2018. [Epub ahead of print] PMID: 30735073 Abstract Supplementation with monounsaturated or omega-3 polyunsaturated fatty acids (n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-week, randomized, double-blind trial examining the effects of orally supplementing ~3g/day of EPA (n=28), DHA (n=28), or OO (n=30) on resting hemodynamics, and in a subset (n=31), MSNA. Both EPA and DHA supplements increased the Omega-3 Index ( P<0.01). Reductions in systolic BP were greater (adjusted intergroup mean difference [95% CI]) following DHA (-3.4 mmHg [-0.9,-5.9], p=0.008) and OO (-3.0 mmHg [-0.5,-5.4], P=0.01) compared to EPA, with no difference between DHA and OO ( P=0.74). Reductions in diastolic BP were greater following DHA (-3.4 mmHg [-1.3,-5.6], p=0.002) and OO (-2.2 mmHg [0.08,-4.3], P=0.04) compared to EPA. EPA increased heart rate compared to DHA (4.2 beats/min, [-0.009,8.4], P=0.05) and OO (4.2 beats/min, [0.08,8.3], P=0.04). MSNA burst frequency was higher following DHA (4 bursts/minute [0.5,8.3], p=0.02) but not OO (-3 bursts/minute [-6,0.6], P=0.2) compared to EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA but not OO increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic over-activation. KEYWORDS: Blood pressure; Dietary Supplement; Omega-3 polyunsaturated fatty acids; Sympathetic nerve activity Seasonal variation of diet quality in a large middle-aged and elderly Dutch population-based cohort. van der Toorn JE, Cepeda M, Kiefte-de Jong JC, Franco OH, Voortman T, Schoufour JD. Eur J Nutr. 2019 Feb 8. doi: 10.1007/s00394-019-01918-5. [Epub ahead of print] PMID: 30734846 https://sci-hub.tw/10.1007/s00394-019-01918-5 Abstract PURPOSE: Several studies have reported seasonal variation in intake of food groups and certain nutrients. However, whether this could lead to a seasonal pattern of diet quality has not been addressed. We aimed to describe the seasonality of diet quality, and to examine the contribution of the food groups included in the dietary guidelines to this seasonality. METHODS: Among 9701 middle-aged and elderly participants of the Rotterdam Study, a prospective population-based cohort, diet was assessed using food-frequency questionnaires (FFQ). Diet quality was measured as adherence to the Dutch dietary guidelines, and expressed in a diet quality score ranging from 0 to 14 points. The seasonality of diet quality and of the food group intake was examined using cosinor linear mixed models. Models were adjusted for sex, age, cohort, energy intake, physical activity, body mass index, comorbidities, and education. RESULTS: Diet quality had a seasonal pattern with a winter-peak (seasonal variation = 0.10 points, December-peak) especially among participants who were men, obese and of high socio-economic level. This pattern was mostly explained by the seasonal variation in the intake of legumes (seasonal variation = 3.52 g/day, December-peak), nuts (seasonal variation = 0.78 g/day, January-peak), sugar-containing beverages (seasonal variation = 12.96 milliliters/day, June-peak), and dairy (seasonal variation = 17.52 g/day, June-peak). CONCLUSIONS: Diet quality varies seasonally with heterogeneous seasonality of food groups counteractively contributing to the seasonal pattern in diet quality. This seasonality should be considered in future research on dietary behavior. Also, season-specific recommendations and policies are required to improve diet quality throughout the year. KEYWORDS: Diet quality; Dietary guidelines; Food frequency questionnaire; Food groups; Seasonality Physical activity modifies the effect of calcium supplements on bone loss in perimenopausal and postmenopausal women: subgroup analysis of a randomized controlled trial. Nakamura K, Saito T, Kobayashi R, Oshiki R, Kitamura K, Watanabe Y. Arch Osteoporos. 2019 Feb 8;14(1):17. doi: 10.1007/s11657-019-0575-4. PMID: 30734085 https://sci-hub.tw/10.1007/s11657-019-0575-4 Abstract We aimed to determine whether the effect of calcium supplements on bone metabolism is modified by physical activity (PA) through a subgroup analysis of an RCT. PA may be a favorable effect modifier of the association between calcium intake and bone loss in perimenopausal and postmenopausal women. PURPOSE: Physical exercise can potentially modify bone metabolism. Here we aimed to determine whether the effect of calcium supplements on bone metabolism is modified by physical activity (PA) through a subgroup analysis of a randomized, double-blind, placebo-controlled trial. METHODS: The trial was conducted over the course of 2 years, and participants were 450 healthy women between 50 and 75 years of age who were randomly assigned to three equally-sized (N = 150 each) groups (500 mg calcium, 250 mg calcium, and placebo). Levels of PA at baseline were evaluated by quantifying moderate (4 METs) and vigorous (6 METs) activities based on a 7-day activity recall, and the total MET-hours per week was calculated. Follow-up BMD examinations were conducted 2 years later. Two-year changes in BMD were compared between the intention-to-treat higher PA subgroup (≥ 10 MET-hours/week) and the lower PA subgroup (< 10 MET-hours/week). RESULTS: Of the 450 participants, 418 underwent follow-up BMD measurements. Regarding the lower PA subgroup, spinal BMD in the 500 mg/day calcium supplement group decreased significantly less (- 0.029 g/cm2, P = 0.042) than in the placebo group (- 0.045 g/cm2), and femoral neck BMD in the 500 mg/day calcium supplement group decreased significantly less (- 0.027 g/cm2, P = 0.049) than in the placebo group (- 0.038 g/cm2). In contrast, changes in neither spinal nor femoral neck BMD significantly differed between the three treatment groups in the higher PA subgroup. CONCLUSIONS: PA is a favorable effect modifier of the association between calcium intake and bone loss in perimenopausal and postmenopausal women with low calcium intake. KEYWORDS: Bone density; Calcium; Physical activity; Postmenopause; Randomized controlled trial Coffee, tea, caffeine, and risk of non-melanoma skin cancer in a Chinese population: The Singapore Chinese Health Study. Oh CC, Jin A, Yuan JM, Koh WP. J Am Acad Dermatol. 2019 Feb 4. pii: S0190-9622(19)30195-1. doi: 10.1016/j.jaad.2019.01.084. [Epub ahead of print] PMID: 30731173 Abstract BACKGROUND: While epidemiological studies in populations of European-descent suggest possible chemo-protective effect of caffeine against non-melanoma skin cancer (NMSC), data in Asian populations are lacking. OBJECTIVES: We examined the relations between coffee, tea and caffeine consumption, and NMSC risk among Chinese in Singapore. METHODS: We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women aged 45-74 years at recruitment from 1993 to 1998. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazard models. RESULTS: Coffee drinking was associated with reduced NMSC risk in a dose-dependent manner (P trend<0.0001); compared with those who drank coffee less than weekly, in those who drank ≥3 cups/day, HRs (95% CIs) were 0.54 (0.31-0.93) for risk of basal cell carcinoma, and 0.33 (0.13-0.84) for risk of squamous cell carcinoma. Compared with non-drinkers, daily drinkers of black tea also had reduced NMSC risk (HR=0.70; 95% CI=0.52-0.94). Caffeine intake reduced NMSC risk in a stepwise manner (P trend=0.0025); subjects with caffeine intake ≥400 mg/day had the lowest risk (HR=0.59; 95% CI=0.34-1.04). CONCLUSION: Consumption of caffeinated drinks such as coffee and black tea may reduce the risk of NMSC among Chinese. KEYWORDS: Chinese; caffeine; coffee; non-melanoma skin cancer; tea Comparative analysis of the gut microbiota in centenarians and young adults shows a common signature across genotypically non-related populations. Tuikhar N, Keisam S, Labala RK, Imrat, Ramakrishnan P, Arunkumar MC, Ahmed G, Biagi E, Jeyaram K. Mech Ageing Dev. 2019 Feb 6. pii: S0047-6374(18)30205-7. doi: 10.1016/j.mad.2019.02.001. [Epub ahead of print] PMID: 30738080 Abstract Gut microbiota is among the factors that may be involved in healthy aging. Broader and geographically spread studies on gut microbiota of centenarians can help in identifying a common signature of longevity. We identified an endogamous Indian population with high centenarian prevalence. Here, we compared the gut microbiota composition and fecal metabolites of a centenarians group (˜100 years) with young people (25-45 years) of the region with the high centenarian prevalence and the nearby region of low centenarian prevalence to decipher microbial-related longevity signatures. Also, we compared our results with publicly available datasets of similar groups including 125 centenarians from three countries (Italy, Japan, China). Our comparative analysis resulted in higher biodiversity within Ruminococcaceae in centenarians, with respect to younger adults, irrespective of their nationality. We observed bacterial signatures that are common among extremely old people of different nationality. Comparative metabolites profiling identified the fecal metabolic signature of extreme aging in the Indian study population. Our analysis of the co-occurrence network and bimodal distribution of several taxa suggested the establishment of a pervasive change in the gut ecology during extreme aging. Our study might pave the way to develop gut microbiota based biomarkers for healthy aging. KEYWORDS: Butyrate; Centenarians; Faecal metabolites; Gut microbiota; Longevity; Naga community; Ruminococcaceae
  15. AlPater

    Al's CR updates

    A Comparison of Dietary and Caloric Restriction Models on Body Composition, Physical Performance, and Metabolic Health in Young Mice. Smith NJ, Caldwell JL, van der Merwe M, Sharma S, Butawan M, Puppa M, Bloomer RJ. Nutrients. 2019 Feb 7;11(2). pii: E350. doi: 10.3390/nu11020350. PMID: 30736418 [See https://www.mdpi.com/2072-6643/11/2/350 for pdf.] Abstract Time-restricted feeding (TRF), alternate day fasting (ADF), and the dietary restriction model known as the Daniel Fast (DF; a vegan/non-processed food diet plan) have garnered attention recently as nutritional interventions to combat obesity. We compared the effects of various dietary models on body composition, physical performance, and metabolic health in C57BL/6 mice. Sixty young C57BL/6 male mice were assigned a diet of TRF, ADF, DF, caloric restriction (CR), a high-fat Western diet (HF) fed ad libitum, or standard rodent chow for eight weeks. Their body composition, run time to exhaustion, fasting glucose, insulin, and glucose tolerance test area under the glucose curve (AUC) were determined. Compared to the HF group, all groups displayed significantly less weight and fat mass gain, as well as non-significant changes in fat-free mass. Additionally, although not statistically significant, all groups displayed greater run time to exhaustion relative to the HF group. Compared to the HF group, all groups demonstrated significantly lower fasting glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), as well as improved glucose tolerance, and the ADF group displayed the best fasting glucose and glucose tolerance results, with DF having the best HOMA-IR. All investigated fasting protocols may improve body composition, measures of insulin sensitivity, and physical performance compared to a high-fat Western diet. The DF and ADF protocols are most favorable with regards to insulin sensitivity and glucose tolerance. Since our selected dietary protocols have also been investigated in humans with success, it is plausible to consider that these dietary models could prove beneficial to men and women seeking improved body composition and metabolic health. KEYWORDS: body composition; diet; exercise; fasting; insulin Effects of Caloric Restriction with Protein Supplementation on Plasma Protein Profiles in Middle-Aged Women with Metabolic Syndrome-A Preliminary Open Study. Chang CY, Tung YT, Lin YK, Liao CC, Chiu CF, Tung TH, Shabrina A, Huang SY. J Clin Med. 2019 Feb 6;8(2). pii: E195. doi: 10.3390/jcm8020195. PMID: 30736312 [See https://www.mdpi.com/2077-0383/8/2/195 for pdf.] Abstract BACKGROUND: Clinical studies have demonstrated that higher protein intake based on caloric restriction (CR) alleviates metabolic abnormalities. However, no study has examined the effects of plasma protein profiles on caloric restriction with protein supplementation (CRPS) in metabolic syndrome (MetS). Therefore, using a proteomic perspective, this pilot study investigated whether CRPS ameliorated metabolic abnormalities associated with MetS in middle-aged women. METHODS: Plasma samples of middle-aged women with MetS in CR (n = 7) and CRPS (n = 6) groups for a 12-week intervention were obtained and their protein profiles were analysed. Briefly, blood samples from qualified participants were drawn before and after the dietary treatment. Anthropometric, clinical, and biochemical variables were measured and correlated with plasma proteomics. RESULTS: In results, we found that body mass index, total body fat, and fasting blood glucose decreased significantly after the interventions but were not different between the CR and CRPS groups. After liquid chromatography⁻tandem mass spectrometry analysis, the relative plasma levels of alpha-2-macroglobulin (A2M), C4b-binding protein alpha chain (C4BPA), complement C1r subcomponent-like protein (C1RL), complement component C6 (C6), complement component C8 gamma chain (C8G), and vitamin K-dependent protein S (PROS) were significantly different between the CRPS and CR groups. These proteins are involved in inflammation, the immune system, and coagulation responses. Moreover, blood low-density lipoprotein cholesterol levels were significantly and positively correlated with C6 plasma levels in both groups. CONCLUSIONS: These findings suggest that CRPS improves inflammatory responses in middle-aged women with MetS. Specific plasma protein expression (i.e., A2M, C4BPA, C1RL, C6, C8G, and PROS) associated with the complement system was highly correlated with fasting blood glucose (FBG), blood lipids (BLs), and body fat. KEYWORDS: caloric restriction; metabolic syndrome; plasma proteomics; protein supplementation