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  1. Low 24-hour core body temperature as a thrifty metabolic trait driving catch-up fat during weight regain after caloric restriction. Calonne J, Arsenijevic D, Scerri I, Miles-Chan JL, Montani JP, Dulloo AG. Am J Physiol Endocrinol Metab. 2019 Aug 20. doi: 10.1152/ajpendo.00092.2019. [Epub ahead of print] PMID: 31430205 Abstract The recovery of body weight after substantial weight loss or growth retardation is often characterized by a disproportionately higher rate of fat mass vs lean mass recovery, with this phenomenon of 'preferential catch-up fat' being contributed by energy conservation (thrifty) metabolism. To test the hypothesis that a low core body temperature (Tc) constitutes a thrifty metabolic trait underlying the high metabolic efficiency driving catch-up fat, the Anipill® system - with the telemetry capsules implanted in the peritoneal cavity - was used for continuous monitoring of Tc for several weeks in a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis. In animals housed at 22°C, 24h Tc was reduced in response to semistarvation (-0.77°C, p<0.001), and remained significantly lower than in controls during the catch-up fat phase of refeeding (-0.27°C on average, p<0.001); the lower Tc during refeeding being more pronounced during the light phase than during the dark phase of the 24h cycle (-0.30°C vs -0.23°C, p<0.01), and with no between-group differences in locomotor activity. A lower 24h Tc in animal showing catch-up fat was also observed when the housing temperature was raised to 29°C (i.e. at thermoneutrality). The reduced energy cost of homeothermy in response to caloric restriction persists during weight recovery, and constitutes a thrifty metabolic trait that contributes to the high metabolic efficiency that underlies the rapid restoration of the body's fat stores during weight regain, with implications for obesity relapse after therapeutic slimming and the pathophysiology of catch-up growth. KEYWORDS: Thermogenesis; Thrifty phenotype; caloric restriction; catch-up growth; obesity Longitudinal analysis of the impact of loneliness on cognitive function over a 20-year follow-up. Wang H, Lee C, Hunter S, Fleming J, Brayne C; CC75C Study Collaboration. Aging Ment Health. 2019 Aug 20:1-7. doi: 10.1080/13607863.2019.1655704. [Epub ahead of print] PMID: 31429312 Abstract Background: Loneliness and cognitive impairment are both commonly experienced by older old people, but evidence for the association between these has been inconsistent. Moreover, most evidence has been cross-sectional in nature and largely based on studies with relatively young later life age groups rather than 'the oldest old'. We aimed to test the potential impact of loneliness amongst older old people on their cognitive function over a 20-year period. Method: Data were drawn from wave 3 to wave 10 of the Cambridge City over-75s Cohort (CC75C) study. The impact of loneliness on transition between normal and impaired cognitive states was examined by multi-state modelling. The associations between loneliness changes and cognitive function decline were tested by using generalized estimating equation (GEE) with an independent working correlation structure. Missing data were imputed by using multiple imputation chained equations. Results: At wave 3, 713 participants were interviewed, of whom 657 (92%) had Mini-Mental State Examination (MMSE) assessments. Of individuals who had an MMSE score, approximately one quarter reported feeling lonely, and another 16% felt slightly lonely. The prevalence of feeling lonely or slightly lonely varied between waves. Results from multi-state modelling indicated that loneliness was not related to cognitive function transitions, and results from the GEE model showed that loneliness was not significantly associated with cognitive function decline after adjusting for cohort effects, follow-up time, sex, education, and interaction terms for sex, education and time. Conclusions: Loneliness did not exert long-term harmful effects on cognitive function in the oldest old. KEYWORDS: Loneliness; cognition; longitudinal analysis; older people The Effect of Pharmaceutical Innovation on Longevity: Patient Level Evidence from the 1996-2002 Medical Expenditure Panel Survey and Linked Mortality Public-use Files. Lichtenberg FR. Forum Health Econ Policy. 2013 Jan 1;16(1):1-33. doi: 10.1515/fhep-2012-0032. PMID: 31419866 Abstract This study uses patient-level data to analyze the effect of technological change embodied in pharmaceuticals on the longevity of elderly Americans. Previous patient-level studies could not control for important patient attributes such as education, income, and race; they did not provide estimates of the effect of using newer drugs on life expectancy, or of the overall cost-effectiveness of new drugs relative to old drugs; and they were not based on nationally representative samples of individuals. Our data, primarily derived from the Medical Expenditure Panel Survey and the Linked Mortality Public-use Files, enable us to overcome those limitations. We investigate the effect of the vintage (year of U.S. Food and Drug Administration approval) of the prescription drugs used by an individual on his or her survival and medical expenditure, controlling for a number of demographic characteristics and indicators and determinants of health status. When we control only for age, sex, and interview year, we estimate that a 1-year increase in drug vintage increases life expectancy by 0.52%. Controlling for a much more extensive set of other attributes (the mean year the person started taking his or her medications, and dummy variables for activity limitations, race, education, family income as a percent of the poverty line, insurance coverage, Census region, body mass index, smoking, and more than 100 medical conditions) has virtually no effect on the estimate of the effect of drug vintage on life expectancy. Between 1996 and 2003, the mean vintage of prescription drugs increased by 6.6 years. This is estimated to have increased the life expectancy of elderly Americans by 0.41-0.47 years. This suggests that not less than two-thirds of the 0.6-year increase in the life expectancy of elderly Americans during 1996-2003 was due to the increase in drug vintage. The 1996-2003 increase in drug vintage is also estimated to have increased annual drug expenditure per elderly American by $207, and annual total medical expenditure per elderly American by $218. This implies that the incremental cost-effectiveness ratio (cost per life-year gained) of pharmaceutical innovation was about $12,900. This estimate of the cost per life-year gained from the use of newer drugs is a small fraction of leading economists' estimates of the value of (willingness to pay for) an additional year of life. It is also consistent with estimates from clinical trials. KEYWORDS: innovation; longevity; mortality; pharmaceuticals; prescription drugs Platelet Indices and Risk of Death and Cardiovascular Events: Results from a Large Population-Based Cohort Study. Patti G, Di Martino G, Ricci F, Renda G, Gallina S, Hamrefors V, Melander O, Sutton R, Engström G, De Caterina R, Fedorowski A. Thromb Haemost. 2019 Aug 20. doi: 10.1055/s-0039-1694969. [Epub ahead of print] PMID: 31430798 Abstract Studies evaluating the relationship between platelet indices and cardiovascular (CV) outcomes yielded conflicting results. We assessed the incidence of adverse events according to baseline quintiles of platelet indices in the prospective cohort of the Malmö Diet and Cancer Study. A total of 30,314 individuals (age 57 ± 8 years) were followed for a median of 16 years (468,490 person-years). Outcome measures included all-cause death, CV death, myocardial infarction (MI), and ischemic stroke. The fifth quintile of platelet count (> 274.6 × 109/L) was associated with higher incidence of all-cause death (hazard ratio {HR} 1.20, 95% confidence interval [CI] 1.09-1.32, p < 0.001), CV death (HR 1.19, 95% CI 1.00-1.42; p = 0.044), MI (HR 1.32, 95% CI 1.12-1.54; p = 0.001), and ischemic stroke (HR 1.27, 95% CI 1.08-1.50, p = 0.004) compared with the first quintile (≤ 185 × 109/L), and also associated with a lower survival, regardless of previous history of MI (p for interaction = 0.58) or stroke (p for interaction = 0.42). In the highest quintile, history of stroke had a higher risk of CV death (HR 3.18, 95% CI 1.54-6.54) compared with no previous stroke (HR 1.12, 95% CI 0.96-1.31). The risk of MI and stroke was greatest in the fifth quintile, regardless of previous MI or previous stroke, respectively. The risk of all adverse events was similar across different quintiles of mean platelet volume. In conclusion, elevated platelet count is associated with higher mortality and risk of CV events, regardless of previous MI and stroke. Platelet count may thus be a useful marker for further stratification of CV risk, and especially of death. Protective Effects of Dietary MUFAs Mediating Metabolites against Hypertension Risk in the Korean Genome and Epidemiology Study. Lee H, Jang HB, Yoo MG, Chung KS, Lee HJ. Nutrients. 2019 Aug 16;11(8). pii: E1928. doi: 10.3390/nu11081928. PMID: 31426326 [pdf availed from PMID site.] Abstract BACKGROUND AND AIMS: Metabolites related to dietary factors can be used to identify biological markers to prevent metabolic disease. However, most studies have been conducted in the United States and Europe, and those in the Asian region are limited. We investigated the effects of dietary monounsaturated fatty acids (MUFAs) and metabolites on new-onset hypertension in the Korean Genome and Epidemiology Study. METHOD AND RESULTS: A total of 1529 subjects without hypertension were divided into tertiles of dietary MUFAs intake. After a 4-year follow-up, 135 serum metabolites were measured using the AbsoluteIDQ p180 kit. During the 4-year follow-up period, 193 new-onset hypertension incidences were observed. The highest MUFAs intake group was inversely associated with the risk of hypertension compared with the lowest MUFAs intake group (odds ratio (OR) = 0.49, (95% confidence interval (CI) = 0.29-0.82)). Of the 135 metabolites, eight were significantly associated with MUFAs intake. Phosphatidylcholine-diacyl (PC aa) C 38:1 and hydroxysphingomyelin (SM OH) C 16:1 were associated with a decrease in hypertension risk (PC aa C 38:1, OR = 0.60 (95% CI = 0.37-0.96); SM OH C 16:1, OR = 0.42 (95% CI = 0.20-0.90)). The highest MUFAs intake group had a significantly decreased risk of hypertension, even considering PC aa C 38:1 and SM (OH) C 16:1 as a mediator. CONCLUSION: We confirmed that dietary MUFAs intake, and PC aa C 38:1 and SM (OH) C 16:1 had protective effects against hypertension. Furthermore, high MUFAs intake combined with PC aa C 38:1 and SM (OH) C 16:1 has the most significant effect on reducing the risk hypertension. KEYWORDS: hypertension; metabolites; monounsaturated fatty acid /MUFAs
  2. Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study. Nayeem F, Chen NW, Nagamani M, Anderson KE, Lu LW. Nutr Res. 2019 Jul 3;68:70-81. doi: 10.1016/j.nutres.2019.06.007. [Epub ahead of print] PMID: 31421395 Abstract Soy isoflavones are potentially beneficial phytoestrogens, but their tissue-selective effects in women are poorly understood. We tested the hypothesis that soy isoflavones affect bone mineral density (BMD), which may be influenced by individual differences in isoflavone metabolism and serum calcium levels. Ninety-nine healthy premenopausal women were randomized to isoflavones (136.6 mg aglycone equivalence) and 98 to placebo for 5 days per week for up to 2 years. BMD, serum calcium, and urinary excretion of daidzein and genistein were measured before and during treatment. In 129 adherent subjects, we found that isoflavone exposure, determined by urinary excretion levels, but not by dose assignment, interacted with serum calcium in affecting whole body BMD, but not hip and spine BMD. The regression coefficient was -0.042 for genistein excretion (GE) and 0.091 for the interaction between GE and serum calcium (all P < .05). Daidzein excretion had similar but marginal effect. Genistein significantly decreased whole body BMD only at low normal serum calcium levels but increased whole body BMD at higher serum calcium levels. Comparing maximum to minimum GE, mean changes in whole body BMD were +0.033 and -0.113 g/cm2 at serum calcium levels of 10 and 8.15 mg/dL, respectively. These associations were not evident by intention-to-treat analysis, which could not model for inter-individual differences in isoflavone metabolism. In summary, soy isoflavones decrease whole body BMD only when serum calcium is low. Isoflavones are dietary substances that may influence calcium homeostasis by releasing calcium from bone while sparing the common fracture risk sites hip and spine. KEYWORDS: Bone metabolism; Calcium homeostasis; Daidzein; Genistein; Hormone receptor modulators; Isoflavones A Prospective Study of Dietary Meat Intake and Risk of Incident Chronic Kidney Disease. Mirmiran P, Yuzbashian E, Aghayan M, Mahdavi M, Asghari G, Azizi F. J Ren Nutr. 2019 Aug 14. pii: S1051-2276(19)30265-1. doi: 10.1053/j.jrn.2019.06.008. [Epub ahead of print] PMID: 31422013 Abstract OBJECTIVE: The aim of the present study was to investigate the association of different meat intake and substitution of them with risk of incident chronic kidney disease (CKD). METHODS: At the baseline, habitual dietary intakes of 4881 participants of the Tehran Lipid and Glucose Study who were free of CKD were assessed by a valid and reliable food-frequency questionnaire. Logistic regression, adjusted for age, sex, smoking, total energy intake, triglycerides, body mass index, physical activity, hypertension, and diabetes, was used to assess the relationship between major protein sources of food (total red meat, unprocessed red meat, and processed red meat) and incident CKD. Odds ratios (ORs) and 95% confidence intervals (CIs) for the CKD were estimated for substituting one serving of total red meat with one serving of low-fat dairy, nuts, whole grains, and legumes. RESULTS: The mean ± standard deviation age of participants was 40.1 ± 12.8 years. After adjustment for confounders, compared with the lowest quartile of total red meat intake, OR of incident CKD in the highest quartile was 1.73 (95% CI: 1.33 to 2.24; P for trend <0.001) in the final model. OR for participants in the highest compared with that in the lowest quartile of processed red meat was 1.99 (95% CI: 2.54 to 2.56; P for trend <0.001). In the substitution analyses, replacing 1 serving of total red meat and processed meat with 1 serving of low-fat dairy, nuts, whole grains, and legumes was associated with a lower risk of incident CKD. CONCLUSIONS: Higher consumption of total red meat and processed meat was associated with increased risk of incident CKD. Furthermore, substitution of total red and processed meat in the diet with other sources of dietary protein was associated with lower CKD risk.
  3. AlPater

    Al's CR updates

    Effects of long-term intermittent versus chronic calorie restriction on oxidative stress in a mouse cancer model. Cicekdal MB, Tuna BG, Charehsaz M, Cleary MP, Aydin A, Dogan S. IUBMB Life. 2019 Aug 19. doi: 10.1002/iub.2145. [Epub ahead of print] PMID: 31424629 https://sci-hub.tw/10.1002/iub.2145 Abstract Calorie restriction (CR) is one of the most effective methods to prevent many diseases including cancer in preclinical models. However, the molecular mechanism of how CR prevents cancer is unclear. The aim of this study was to understand the role of oxidative stress (OS) in the preventive effects of different types of CR in aging mouse mammary tumor virus-transforming growth factor-alpha (MMTV-TGF-α) female mice. Mice were enrolled in ad libitum (AL), chronic CR (CCR, 15% CR) or intermittent CR [ICR, 3 weeks AL (ICR-Refeed, ICR-RF) and 1 week 60% CR (ICR-Restriction, ICR-R) in cyclic periods] groups started at the age of 10 weeks and continued until 81/82 weeks of age. Blood samples were collected to measure malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels. There was no significant difference for MDA levels among the dietary groups although the chronic calorie restriction (CCR) group had lower MDA levels compared to intermittent calorie restriction (ICR) and AL group at different time points. There was also no change in MDA levels of CCR group with aging. On the other hand, the CCR group had higher CAT and SOD activity compared to ICR-R, ICR-RF, and AL groups. Moreover, GSH level was higher in CCR compared to ICR group at week 49/50 (p < .05). CAT and SOD activities were also positively correlated (p < .05). Here, for the first time, the long-term (72 weeks) effects of different types of CR on OS parameters were reported. In conclusion, moderate that is, 15%, CCR is more likely to be protective compared to the same overall calorie deficit implemented by ICR against OS that may play role in the preventive effects of CR. KEYWORDS: MMTV-TGF-α mice; breast cancer; energy restriction; intermittent calorie restriction; mammary tumor; oxidative stress
  4. I would say that a higher level is an overall advantage: Hematological parameters and all-cause mortality: a prospective study of older people. Frąckiewicz J, Włodarek D, Brzozowska A, Wierzbicka E, Słowińska MA, Wądołowska L, Kałuża J. Aging Clin Exp Res. 2018 May;30(5):517-526. doi: 10.1007/s40520-017-0791-y. Epub 2017 Jun 29. PMID: 28664457 Free PMC Article Abstract BACKGROUND: The effect of low and high concentration of some hematological parameters in the blood can have a negative impact on health. AIM: Therefore, we investigated the associations between hematological parameters and all-cause mortality among older people living in Poland. METHODS: The study was carried out among 75-80-year-old participants (n = 403) from Warsaw and Olsztyn regions, Poland. Information on lifestyle factors and food consumption were obtained at baseline (June 1, 1999) using a self-administered questionnaire. Red blood cell, haemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC) were determined. The data on deaths from all-causes were collected from the baseline until October 31, 2006. During an average of 7.4 years of follow-up, we ascertained 154 cases of death from all-causes. RESULTS: Compared with men in the lowest tertile of MCV, MCH, and MCHC, the multivariable hazard ratios (HRs) of all-cause mortality in those in the highest tertile were 0.35 (95% CI, 0.17-0.73), 0.32 (95% CI, 0.16-0.67), and 0.44 (95% CI, 0.22-0.88), respectively. In contrast, among women after combining the second and the third tertiles of MCV, MCH, and MCHC, the HRs were 2.01 (95% CI, 1.01-3.99), 1.71 (95% CI, 0.85-3.43), and 1.09 (95% CI, 0.62-1.94), respectively. DISCUSSION/CONCLUSION: We observed inverse associations between some hematological parameters and all-cause mortality among men, but not among women. This may be explained by a difference in iron metabolism, iron status, hormone regulations, or the occurrence of some diseases. KEYWORDS: Gender; Hematological parameters; Mortality; Older people; Prospective study
  5. Nutritional Risk Factors, Microbiota and Parkinson's Disease: What Is the Current Evidence? Boulos C, Yaghi N, El Hayeck R, Heraoui GN, Fakhoury-Sayegh N. Nutrients. 2019 Aug 14;11(8). pii: E1896. doi: 10.3390/nu11081896. Review. PMID: 31416163 [pdf availed from Pubmed site.] Abstract Parkinson's disease (PD) is a frequent neurodegenerative disease among elderly people. Genetic and underlying environmental factors seem to be involved in the pathogenesis of PD related to degeneration of dopaminergic neurons in the striatum. In previous experimental researches oxidative stress, mitochondrial dysfunction, homocysteine, and neuroinflammation have been reported as potential mechanisms. Among environmental factors, nutrition is one of the most investigated areas as it is a potentially modifiable factor. The purpose of this review is to provide current knowledge regarding the relation between diet and PD risk. We performed a comprehensive review including the most relevant studies from the year 2000 onwards including prospective studies, nested case-control studies, and meta-analysis. Among dietary factors we focused on specific nutrients and food groups, alcoholic beverages, uric acid, and dietary patterns. Furthermore, we included studies on microbiota as recent findings have shown a possible impact on neurodegeneration. As a conclusion, there are still many controversies regarding the relationship between PD and diet which, beside methodological differences among studies, may be due to underlying genetic and gender-specific factors. However, some evidence exists regarding a potential protective effect of uric acid, poly-unsaturated fatty acids, coffee, and tea but mainly in men, whereas dairy products, particularly milk, might increase PD risk through contaminant mediated effect. KEYWORDS: Parkinson’s disease; dietary factors; neurodegenerative diseases
  6. Polyphenols and Metabolites Enhance Survival in Rodents and Nematodes-Impact of Mitochondria. Dilberger B, Passon M, Asseburg H, Silaidos CV, Schmitt F, Schmiedl T, Schieber A, Eckert GP. Nutrients. 2019 Aug 13;11(8). pii: E1886. doi: 10.3390/nu11081886. PMID: 31412639 https://www.mdpi.com/2072-6643/11/8/1886/htm Abstract (1) Background: Polyphenols (PP) play an important role in the prevention of non-communicable diseases and may contribute to healthy aging. To investigate the molecular and cellular aspects of PP metabolites on longevity with a focus on mitochondrial function, we applied a pre-fermented mixture of polyphenols (Rechtsregulat®, RR) to rodents and nematodes. (2) Methods: The lifespans of Navar Medical Research Institute (NMRI) mice and C. elegans were recorded. The heat-stress resistance (37 °C) of C. elegans N2 was measured using nucleic staining. Respiration and membrane potential (ΔΨm) were measured in isolated mitochondria. The energetic metabolites adenosine triphosphate (ATP), lactate, and pyruvate were determined in lysates. Expression levels of longevity related genes were determined using quantitative real time polymerase chain reaction (qRT-PCR). Phenolic compounds were identified using ultra high performance liquid chromatography-diode array detection-Iontrap-multiple stage mass spectrometry (UHPLC-DAD-Iontrap-MSn). (3) Results: Several phenolic metabolites including protocatechuic acid (PCA) were identified in RR. Feeding of mice with RR resulted in a significantly increased lifespan. Heat-stress resistance (RR *** p = 0.0006; PCA **** p < 0.0001), median lifespan (NMRI: RR ** p = 0.0035; C. elegans RR * p = 0.0279; PCA **** p < 0.0001), and activity of mitochondrial respiratory chain complexes (RR *-** p = 0.0237 - 0.0052; PCA * p = 0.019 - 0.0208) of C. elegans were significantly increased after incubation with RR (10%) or PCA (780 µM). PCA significantly improved nematodes ΔΨm (* p = 0.02058) and ATP levels (* p = 0.029). RR significantly up-regulated lactate levels, indicating enhanced glycolysis. The expression levels of longevity related genes daf-16, sir-2.1, and skn-1 were significantly upregulated after PCA, and partially after RR administration. (4) Conclusion: Phenolic metabolites such as PCA have the potential to enhance health and lifespan and mitochondrial function, and thus may contribute to healthy aging. KEYWORDS: caenorhabditis elegans; longevity; mitochondria; polyphenol; protocatechuic acid; respiration Improvement of cognitive functions by oral intake of Hericium erinaceus. Saitsu Y, Nishide A, Kikushima K, Shimizu K, Ohnuki K. Biomed Res. 2019;40(4):125-131. doi: 10.2220/biomedres.40.125. PMID: 31413233 Abstract Hericium erinaceus has been recognized as medical mushroom since ancient time, but its scientific evidence for human health has been still uncertain. In this study, we tested a randomized, double-blind, placebo-controlled parallel-group comparative study to evaluate the improvement of the cognitive functions by taking supplements containing fruiting body of H. erinaceus for 12 weeks. We performed three kinds of tests: Mini Mental State Examination (MMSE), Benton visual retention test, and Standard verbal paired-associate learning test (S-PA). MMSE alone showed that oral intake of H. erinaceus significantly improved cognitive functions and prevented from the deterioration. We speculate that various chemical compounds, including hericenones, in the mushroom have multiple effects to the brain neural networks and improve cognitive functions. Oral intake of H.erinaceus is safe and convenient method for dementia prevention so far. >>>>>>>> https://www.crsociety.org/topic/11801-als-papers-citations-and-possibly-links-and-excerpts-or-my-synopses/?page=7&tab=comments#comment-20947
  7. AlPater

    Al's CR updates

    Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis. Matai L, Sarkar GC, Chamoli M, Malik Y, Kumar SS, Rautela U, Jana NR, Chakraborty K, Mukhopadhyay A. Proc Natl Acad Sci U S A. 2019 Aug 14. pii: 201900055. doi: 10.1073/pnas.1900055116. [Epub ahead of print] PMID: 31413197 https://www.pnas.org/content/early/2019/08/13/1900055116 Abstract Unfolded protein response (UPR) of the endoplasmic reticulum (UPRER) helps maintain proteostasis in the cell. The ability to mount an effective UPRER to external stress (iUPRER) decreases with age and is linked to the pathophysiology of multiple age-related disorders. Here, we show that a transient pharmacological ER stress, imposed early in development on Caenorhabditis elegans, enhances proteostasis, prevents iUPRER decline with age, and increases adult life span. Importantly, dietary restriction (DR), that has a conserved positive effect on life span, employs this mechanism of ER hormesis for longevity assurance. We found that only the IRE-1-XBP-1 branch of UPRER is required for the longevity effects, resulting in increased ER-associated degradation (ERAD) gene expression and degradation of ER resident proteins during DR. Further, both ER hormesis and DR protect against polyglutamine aggregation in an IRE-1-dependent manner. We show that the DR-specific FOXA transcription factor PHA-4 transcriptionally regulates the genes required for ER homeostasis and is required for ER preconditioning-induced life span extension. Finally, we show that ER hormesis improves proteostasis and viability in a mammalian cellular model of neurodegenerative disease. Together, our study identifies a mechanism by which DR offers its benefits and opens the possibility of using ER-targeted pharmacological interventions to mimic the prolongevity effects of DR. KEYWORDS: aging; dietary restriction; endoplasmic reticulum; hormesis; life span Impact of dietary fat and sucrose consumption on cardiac fibrosis in mice and rhesus monkeys. Natarajan N, Vujic A, Das J, Wang AC, Phu KK, Kiehm SH, Ricci-Blair EM, Zhu AY, Vaughan KL, Colman RJ, Mattison JA, Lee RT. JCI Insight. 2019 Aug 15. pii: 128685. doi: 10.1172/jci.insight.128685. [Epub ahead of print] PMID: 31415241 https://insight.jci.org/articles/view/128685/pdf Abstract Calorie restriction (CR) improved healthspan in two longitudinal studies in nonhuman primates (NHPs), yet only the University of Wisconsin (UW) study demonstrated an increase in survival in CR monkeys relative to controls; the National Institute on Aging (NIA) study did not. Here, analysis of left ventricle samples showed that CR did not reduce cardiac fibrosis relative to controls. However, there was a 5.9-fold increase of total fibrosis in UW hearts, compared to NIA. Diet composition was a prominent difference between the studies; therefore, we used the NHP diets to characterize diet-associated molecular and functional changes in the hearts of mice. Consistent with the findings from the NHP samples, mice fed UW or a modified NIA diet with increased sucrose and fat developed greater cardiac fibrosis compared to the NIA diet, and transcriptomics analysis revealed diet-induced activation of myocardial oxidative phosphorylation and cardiac muscle contraction pathways. KEYWORDS: Aging; Cardiology; Cardiovascular disease; Fibrosis
  8. Postprandial Responses of Serum Bile Acids in Healthy Humans After Ingestion of Turmeric Before Medium /High-Fat Breakfasts. Ghaffarzadegan T, Zanzer YC, Östman E, Hållenius F, Essén S, Sandahl M, Nyman M. Mol Nutr Food Res. 2019 Aug 14:e1900672. doi: 10.1002/mnfr.201900672. [Epub ahead of print] PMID: 31411373 https://sci-hub.tw/10.1002/mnfr.201900672 Abstract SCOPE: Bile acids (BAs) are known to regulate a number of metabolic activities in the body. However, very little is known about how BAs are affected by diet. This study aimed to investigate whether a single-dose of turmeric-based beverage (TUR) before ingestion of medium- (MF) or high-fat (HF) breakfasts would improve the BA profile in healthy subjects. METHODS AND RESULTS: Twelve healthy subjects were assigned to a randomized crossover single-blind study. The subjects received iso-caloric MF or HF breakfasts after a drink containing flavored water with or without an extract of turmeric with at least one-week wash-out period between the treatments. Postprandial BAs were measured using protein precipitation followed by ultra-high-performance liquid chromatography-mass spectrometry analysis (UHPLC-MS). The concentration of BAs was generally higher after HF than MF breakfasts. Ingestion of TUR before MF breakfast increased the serum concentrations of free and conjugated forms of cholic and ursodeoxycholic acids, as well as the concentrations of chenodeoxycholic acid and its taurine-conjugated form. However, the concentration of conjugated forms of deoxycholic acid decreased when TUR was taken before HF breakfast. CONCLUSION: TUR ingestion before MF and HF breakfasts improved BA profiles and may therefore have potential health-promoting effects on BA metabolism. KEYWORDS: Curcumin; mass spectrometry; postprandial bile acids; turmeric; ultra-high-performance liquid chromatography
  9. General and Abdominal Adiposity and Mortality in Mexico City: Prospective Study of 150 000 Adults. Gnatiuc L, Alegre-Díaz J, Wade R, Ramirez-Reyes R, Tapia-Conyer R, Garcilazo-Ávila A, Chiquete E, Gonzáles-Carballo C, Solano-Sanchez M, Clarke R, Collins R, Herrington WG, Hill M, Lewington S, Peto R, Emberson JR, Kuri-Morales P. Ann Intern Med. 2019 Aug 13. doi: 10.7326/M18-3502. [Epub ahead of print] PMID: 31404923 Abstract BACKGROUND: Some reports suggest that body mass index (BMI) is not strongly associated with mortality in Hispanic populations. OBJECTIVE: To assess the causal relevance of adiposity to mortality in Mexican adults, avoiding reverse causality biases. DESIGN: Prospective study. SETTING: 2 Mexico City districts. PARTICIPANTS: 159 755 adults aged 35 years and older at recruitment, followed for up to 14 years. Participants with a hemoglobin A1c level of 7% or greater, diabetes, or other chronic diseases were excluded. MEASUREMENTS: BMI, waist-to-hip ratio, waist circumference, and cause-specific mortality. Cox regression, adjusted for confounders, yielded mortality hazard ratios (HRs) after at least 5 years of follow-up and before age 75 years. RESULTS: Among 115 400 participants aged 35 to <75 years at recruitment, mean BMI was 28.0 kg/m2 (SD, 4.1 kg/m2) in men and 29.6 kg/m2 (SD, 5.1 kg/m2) in women. The association of BMI at recruitment with all-cause mortality was J-shaped, with the minimum at 25 to <27.5 kg/m2. Above 25 kg/m2, each 5-kg/m2 increase in BMI was associated with a 30% increase in all-cause mortality (HR, 1.30 [95% CI, 1.24 to 1.36]). This association was stronger at ages 40 to <60 years (HR, 1.40 [CI, 1.30 to 1.49]) than at ages 60 to <75 years (HR, 1.24 [CI, 1.17 to 1.31]) but was not materially affected by sex, smoking, or other confounders. The associations of mortality with BMI and waist-to-hip ratio were similarly strong, and each was weakened only slightly by adjustment for the other. Waist circumference was strongly related to mortality and remained so even after adjustment for BMI and hip circumference. LIMITATIONS: Analyses were limited to mortality. CONCLUSION: General, and particularly abdominal, adiposity were strongly associated with mortality in this Mexican population. Heart rate and premature atrial contractions at 24hECG independently predict atrial fibrillation in a population-based study. Persson AP, Fedorowski A, Hedblad B, Persson M, Juul-Möller S, Engström G, Johnson LSB. Heart. 2019 Aug 12. pii: heartjnl-2019-315119. doi: 10.1136/heartjnl-2019-315119. [Epub ahead of print] PMID: 31405897 Abstract BACKGROUND: Low resting heart rate and premature atrial contractions (PACs) predict incident atrial fibrillation (AF) and could be interdependent, since PACs occur in the gaps between normal beats. OBJECTIVE: To study the association between low heart rate at 24hECG, PACs and incident AF in a prospective population-based cohort. METHODS: In the Malmö Diet and Cancer study, 24hECGs were performed in 377 AF-free subjects. The endpoint was clinical AF retrieved from national hospital (mean follow-up 17 years). The interaction between increased supraventricular activity (SVA) top quartile of either PACs/hour or supraventricular tachycardias/hour) and mean heart rate (mHR) as regards AF risk was assessed in multivariable Cox regression analyses adjusted for age, sex, height, BMI, systolic blood pressure, antihypertensive medication, smoking and homeostasis model assessment of insulin resistance. RESULTS: There were 80 (21%) incident cases of AF. Below median mHR (80 bpm/75 bpm for women/men) was associated with increased AF incidence (HR: 1.89, 95% CI 1.18 to 3.02, p=0.008). There was no correlation between mHR and SVA (p=0.6) or evidence of a multiplicative interaction between these factors for AF risk (p for interaction=0.6) In the group with both increased SVA and below median mHR (17% of the population) the relative risk of AF was very high (HR 4.5, 95% CI 2.2 to 9.1, p=0.001). CONCLUSION: Low mHR at 24hECG independently predicts AF, but there is no association between mHR and SVA, and these factors are independent as regards AF risk. Subjects with both low mHR and increased SVA have high AF risk. KEYWORDS: 24h-electrocardiogram; atrial fibrillation; heartrate; population; supraventricular ectopy, premature atrial contraction
  10. AlPater

    Al's CR updates

    Effects of Moderate Chronic Food Restriction on the Development of Postprandial Dyslipidemia with Ageing. Fernández A, Mazuecos L, Pintado C, Rubio B, López V, de Solís AJ, Rodríguez M, Andrés A, Gallardo N. Nutrients. 2019 Aug 10;11(8). pii: E1865. doi: 10.3390/nu11081865. PMID: 31405194 https://www.mdpi.com/2072-6643/11/8/1865/htm Abstract Ageing is a major risk factor for the development of metabolic disorders linked to dyslipidemia, usually accompanied by increased adiposity. The goal of this work was to investigate whether avoiding an excessive increase in adiposity with ageing, via moderate chronic food restriction (FR), ameliorates postprandial dyslipidemia in a rat model of metabolic syndrome associated with ageing. Accordingly, we performed an oral lipid loading test (OLLT) in mature middle-aged (7 months) and middle-old-aged (24 months) Wistar rats fed ad libitum (AL) or under moderate FR for 3 months. Briefly, overnight fasted rats were orally administered a bolus of extra-virgin olive oil (1 mL/Kg of body weight) and blood samples were taken from the tail vein before fat load (t = 0) and 30, 60, 90, 120, 180, and 240 min after fat administration. Changes in serum lipids, glucose, insulin, and glucagon levels were measured at different time-points. Expression of liver and adipose tissue metabolic genes were also determined before (t = 0) and after the fat load (t = 240 min). Postprandial dyslipidemia progressively increased with ageing and this could be associated with hepatic ChREBP activity. Interestingly, moderate chronic FR reduced adiposity and avoided excessive postprandial hypertriglyceridemia in 7- and 24-month-old Wistar rats, strengthening the association between postprandial triglyceride levels and adiposity. The 24-month-old rats needed more insulin to maintain postprandial normoglycemia; nevertheless, hyperglycemia occurred at 240 min after fat administration. FR did not alter the fasted serum glucose levels but it markedly decreased glucagon excursion during the OLLT and the postprandial rise of glycemia in the 24-month-old rats, and FGF21 in the 7-month-old Wistar rats. Hence, our results pointed to an important role of FR in postprandial energy metabolism and insulin resistance in ageing. Lastly, our data support the idea that the vWAT might function as an ectopic site for fat deposition in 7-month-old and in 24-month-old Wistar rats that could increase their browning capacity in response to an acute fat load. KEYWORDS: ChREBP; adipose tissue; ageing; oral lipid loading test; postprandial hypertrigliceridemia; postprandial thermogenesis Fasting and rapamycin: diabetes versus benevolent glucose intolerance. Blagosklonny MV. Cell Death Dis. 2019 Aug 13;10(8):607. doi: 10.1038/s41419-019-1822-8. Review. PMID: 31406105 https://www.nature.com/articles/s41419-019-1822-8 Abstract Rapamycin (Sirolimus) slows aging, extends life span, and prevents age-related diseases, including diabetic complications such as retinopathy. Puzzlingly, rapamycin can induce insulin sensitivity, but may also induce insulin resistance or glucose intolerance without insulin resistance. This mirrors the effect of fasting and very low calorie diets, which improve insulin sensitivity and reverse type 2 diabetes, but also can cause a form of glucose intolerance known as benevolent pseudo-diabetes. There is no indication that starvation (benevolent) pseudo-diabetes is detrimental. By contrast, it is associated with better health and life extension. In transplant patients, a weak association between rapamycin/everolimus use and hyperglycemia is mostly due to a drug interaction with calcineurin inhibitors. When it occurs in cancer patients, the hyperglycemia is mild and reversible. No hyperglycemic effects of rapamycin/everolimus have been detected in healthy people. For antiaging purposes, rapamycin/everolimus can be administrated intermittently (e.g., once a week) in combination with intermittent carbohydrate restriction, physical exercise, and metformin.
  11. Trajectories of body mass index in adulthood and all-cause and cause-specific mortality in the Melbourne Collaborative Cohort Study. Yang Y, Dugué PA, Lynch BM, Hodge AM, Karahalios A, MacInnis RJ, Milne RL, Giles GG, English DR. BMJ Open. 2019 Aug 10;9(8):e030078. doi: 10.1136/bmjopen-2019-030078. PMID: 31401610 https://bmjopen.bmj.com/content/9/8/e030078.long https://bmjopen.bmj.com/content/bmjopen/9/8/e030078.full.pdf Abstract OBJECTIVE: Limited research has assessed the association between patterns of body mass index (BMI) change across adulthood and mortality. We aimed to identify groups of individuals who followed specific group-based BMI trajectories across adulthood, using weight collected on three occasions and recalled data from early adulthood, and to examine associations with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Melbourne, Australia. PARTICIPANTS: Adults (n=29 881) enrolled in the Melbourne Collaborative Cohort Study, who were aged from 40 to 70 years between 1990 and 1994, and had BMI data for at least three time points. OUTCOME: Deaths from any cause before 31 March 2017 and deaths from obesity-related cancers, cardiovascular diseases (CVDs) and other causes before 31 December 2013. RESULTS: We identified six group-based BMI trajectories: lower-normal stable (TR1), higher-normal stable (TR2), normal to overweight (TR3), chronic borderline obesity (TR4), normal to class I obesity (TR5) and overweight to class II obesity (TR6). Generally, compared with maintaining lower-normal BMI throughout adulthood, the lowest mortality was experienced by participants who maintained higher-normal BMI (HR 0.90; 95% CI 0.84 to 0.97); obesity during midlife was associated with higher all-cause mortality even when BMI was normal in early adulthood (HR 1.09; 95% CI 0.98 to 1.21) and prolonged borderline obesity from early adulthood was also associated with elevated mortality (HR 1.16; 95% CI 1.01 to 1.33). These associations were stronger for never-smokers and for death due to obesity-related cancers. Being overweight in early adulthood and becoming class II obese was associated with higher CVD mortality relative to maintaining lower-normal BMI (HR 2.27; 95% CI 1.34 to 3.87). CONCLUSION: Our findings highlight the importance of weight management throughout adulthood to reduce mortality. KEYWORDS: epidemiology; preventive medicine; public health
  12. AlPater

    Al's CR updates

    Short-term dietary restriction in old mice rejuvenates the aging-induced structural imbalance of gut microbiota. Zeng T, Cui H, Tang D, Garside GB, Wang Y, Wu J, Tao Z, Zhang L, Tao S. Biogerontology. 2019 Aug 10. doi: 10.1007/s10522-019-09830-5. [Epub ahead of print] PMID: 31401701 Abstract The world's aging population is growing rapidly. Incidences of multiple pathologies, such as abdominal obesity, cardiovascular and cerebrovascular diseases, type 2 diabetes, and malignant neoplasms, increase sharply with age. Aged individuals possess a significantly shifted composition of gut microbiota, which is suggested to play important roles in aging associated pathologies. Whether the existing shifted structural composition of microbiota in aged populations can be reverted non-pharmacologically has not been studied so far. Here, we show an intestinal flora imbalance in old C57BL/6J mice with a remarkable dominant proportion of microbes promoting lipid metabolism and inflammation. Intriguingly, short-term (2 months) dietary restriction was enough to significantly revert the imbalance of intestinal flora in aged mice toward a more balanced structural composition as shown in young mice. ... Our study provides the first evidence that short-term dietary restriction in old mice can restore the already dysfunctional aged gut microbiota, which may help ameliorate aging-related disorders plaguing the vast elderly population. KEYWORDS: Aging; Dietary restriction; Gut microbiota; Inflammation; Obesity; Rejuvenate
  13. Association of BMI, smoking and alcohol with multiple myeloma mortality in Asians: a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium. Ugai T, Ito H, Oze I, Saito E, Rahman MS, Boffetta P, Gupta PC, Sawada N, Tamakoshi A, Shu XO, Koh WP, Gao YT, Sadakane A, Tsuji I, Park SK, Nagata C, You SL, Pednekar MS, Tsugane S, Cai H, Yuan JM, Xiang YB, Ozasa K, Tomata Y, Kanemura S, Sugawara Y, Wada K, Chen CJ, Yoo KY, Chia KS, Ahsan H, Zheng W, Inoue M, Kang D, Potter JD, Matsuo K. Cancer Epidemiol Biomarkers Prev. 2019 Aug 9. pii: cebp.0389.2019. doi: 10.1158/1055-9965.EPI-19-0389. [Epub ahead of print] PMID: 31399476 Abstract BACKGROUND: To date, few epidemiological studies have been conducted to elucidate lifestyle-related risk factors for multiple myeloma (MM) in Asia. We investigated the association of body mass index (BMI), smoking, and alcohol intake with the risk of MM mortality through a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium. METHODS: The analysis included 805,309 participants contributing 10,221,623 person-years of accumulated follow-up across Asia Cohort Consortium cohorts. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between BMI, smoking and alcohol at baseline and the risk of MM mortality were assessed using a Cox proportional hazards model with shared frailty. RESULTS: We observed a statistically significant dose-dependent association between BMI categories and the risk of MM mortality (<18.5 kg/m2: HR=0.80, 95% CI: 0.52-1.24; 18.5 to 24.9 kg/m2: reference; 25.0 to 29.9 kg/m2: HR=1.17, 0.94-1.47; ≥30 kg/m2: HR=1.61, 0.99-2.64, p for trend=0.014). By sex, this association was more apparent in women than in men (P for heterogeneity between sexes=0.150). We observed no significant associations between smoking or alcohol consumption and risk of MM mortality. CONCLUSION: This study showed that excess body mass is associated with an increased risk of MM mortality among Asian populations. In contrast, our results do not support an association between smoking or alcohol consumption and the risk of MM mortality in Asian populations. IMPACT: This study provides important evidence on the association of BMI, smoking and alcohol with the risk of MM mortality in Asian populations.
  14. Variation of all-cause and cause-specific mortality with body mass index in one million Swedish parent-son pairs: An instrumental variable analysis. Wade KH, Carslake D, Tynelius P, Davey Smith G, Martin RM. PLoS Med. 2019 Aug 9;16(8):e1002868. doi: 10.1371/journal.pmed.1002868. eCollection 2019 Aug. PMID: 31398184 Abstract BACKGROUND: High body mass index (BMI) is associated with mortality, but the pervasive problem of confounding and reverse causality in observational studies limits inference about the direction and magnitude of causal effects. We aimed to obtain estimates of the causal association of BMI with all-cause and cause-specific mortality. METHODS AND FINDINGS: In a record-linked, intergenerational prospective study from the general population of Sweden, we used two-sample instrumental variable (IV) analysis with data from 996,898 fathers (282,407 deaths) and 1,013,083 mothers (153,043 deaths) and their sons followed up from January 1, 1961, until December 31, 2004. Sons' BMI was used as the instrument for parents' BMI to compute hazard ratios (HRs) for risk of mortality per standard deviation (SD) higher parents' BMI. Using offspring exposure as an instrument for parents' exposure is unlikely to be affected by reverse causality (an important source of bias in this context) and reduces confounding. IV analyses supported causal associations between higher BMI and greater risk of all-cause mortality (HR [95% confidence interval (CI)] per SD higher fathers' BMI: 1.29 [1.26-1.31] and mothers' BMI: 1.39 [1.35-1.42]) and overall cancer mortality (HR per SD higher fathers' BMI: 1.20 [1.16-1.24] and mothers' BMI: 1.29 [1.24-1.34]), including 9 site-specific cancers in men (bladder, colorectum, gallbladder, kidney, liver, lung, lymphatic system, pancreas, and stomach) and 11 site-specific cancers in women (gallbladder, kidney, liver, lung, lymphatic system, ovaries, pancreas, stomach, uterus, cervix, and endometrium). There was evidence supporting causal associations between higher BMI in mothers and greater risk of mortality from kidney disease (HR: 2.17 [1.68-2.81]) and lower risk of mortality from suicide (HR: 0.77 [0.65-0.90]). In both sexes, there was evidence supporting causal associations between higher BMI and mortality from cardiovascular diseases (CVDs), stroke, diabetes, and respiratory diseases. We were unable to test the association between sons' and mothers' BMIs (as mothers' data were unavailable) or whether the instrument was independent of unmeasured or residual confounding; however, the associations between parents' mortality and sons' BMI were negligibly influenced by adjustment for available confounders. CONCLUSIONS: Consistent with previous large-scale meta-analyses and reviews, results supported the causal role of higher BMI in increasing the risk of several common causes of death, including cancers with increasing global incidence. We also found positive effects of BMI on mortality from respiratory disease, prostate cancer, and lung cancer, which has been inconsistently reported in the literature, suggesting that the causal role of higher BMI in mortality from these diseases may be underestimated. Furthermore, we expect different patterns of bias in the current observational and IV analyses; therefore, the similarities between our findings from both methods increases confidence in the results. These findings support efforts to understand the mechanisms underpinning these effects to inform targeted interventions and develop population-based strategies to reduce rising obesity levels for disease prevention. Co-ingestion of Black Tea Reduces the Indispensable Amino Acid Digestibility of Hens' Egg in Indian Adults. Kashyap S, Shivakumar N, Varkey A, Preston T, Devi S, Kurpad AV. J Nutr. 2019 Aug 1;149(8):1363-1368. doi: 10.1093/jn/nxz091. PMID: 31127832 Free PMC Article Abstract BACKGROUND: Tea, a commonly consumed beverage, contains high amounts of polyphenols that can impair protein digestibility, as demonstrated in vitro. There are no human studies examining the inhibitory influence of tea polyphenols (TPP) on high-quality protein digestibility. OBJECTIVE: The aim of this study was to determine the effect of black tea on the true indispensable amino acid (IAA) digestibility of whole boiled egg protein, in healthy adult humans, through use of a dual isotope tracer approach. METHODS: The effect of black TPP (4.6 mg/mL, ingested as a beverage with the meal) on 2H-labeled whole boiled egg protein, administered with ghee rice and tomato curry, was measured with reference to 13C-spirulina protein in healthy Indian adults aged 20-27 y of both sexes with BMI of 22.0 ± 2.8 kg/m2. The results were then compared to previously determined whole egg mean IAA digestibility measured by the same method, without black tea, in the same subjects (n = 5). To correct for any independent effect of TPP on spirulina protein (used as a standard protein), the true IAA digestibility of 13C-spirulina protein was independently measured with reference to a 2H-amino acid mixture, with and without co-ingestion of black tea, in 3 of the same subjects. RESULTS: The true IAA digestibility of whole boiled egg protein significantly decreased by 17% when co-ingested with black tea. However, there was no significant reduction in the true IAA digestibility of spirulina protein when co-ingested with black tea. CONCLUSIONS: TPP protein interactions reduced whole egg digestibility in healthy Indian adults but had minimal effect on spirulina protein digestibility. In populations who are at risk of dietary quality protein inadequacy, the consumption of tea during or after a meal can further increase the risk of inadequacy. KEYWORDS: black tea; dual isotope tracer technique; intrinsically labeled egg; tea polyphenol; true indispensable amino acid digestibility Intake of Dietary Fiber, Fruits, and Vegetables and Risk of Diverticulitis. Ma W, Nguyen LH, Song M, Jovani M, Liu PH, Cao Y, Tam I, Wu K, Giovannucci EL, Strate LL, Chan AT. Am J Gastroenterol. 2019 Aug 7. doi: 10.14309/ajg.0000000000000363. [Epub ahead of print] PMID: 31397679 Abstract OBJECTIVES: Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis in a large cohort of women. METHODS: We followed 50,019 women in the Nurses' Health Study (1990-2014) who were aged 43-70 years and free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records. RESULTS: We documented 4,343 incident cases of diverticulitis, encompassing 1,106,402 person-years of follow-up. Compared with participants in the lowest quintile, the multivariable hazard ratio of diverticulitis in the highest quintile of total fiber intake was 0.86 (95% confidence interval: 0.78-0.95; P-trend = 0.002). Fiber from fruits and cereals, but not vegetables, was associated with a decreased risk of diverticulitis. Furthermore, intake of total whole fruit intake and specific fruits such as apples/pears and prunes were associated with reduced risk of diverticulitis with a multivariable hazard ratio for diverticulitis of 0.95 (0.92-0.98; P-trend < 0.001) for every serving increase of total whole fruit intake per day. DISCUSSION: Higher intake of dietary fiber and fiber from different food sources, except for vegetable fiber, are associated with a lower risk of diverticulitis in women. A greater intake of whole fruit is also associated with reduced risk. Chronic Consumption of a Commercial Energy Drink Reduces Blood Pressure in Normotensive Wild-Type Mice. Graneri L, D'Alonzo Z, Lam V, Mamo J, Dhaliwal S, Takechi R. Front Nutr. 2019 Jul 23;6:111. doi: 10.3389/fnut.2019.00111. eCollection 2019. PMID: 31396518 Abstract Objective: Studies report that acute consumption of energy drinks transiently increases blood pressure (BP). However, few studies report the effect of chronic energy drink consumption on BP. In this study, we investigated the effects of long-term energy drink ingestion on BP in C57BL/6J normotensive wild-type mice. Research Methods and Procedures: Groups of mice were randomized to no treatment (water) (Control group), or to Mother™ provided as a decarbonated 30% (v/v) drinking solution (Energy Drink group), sugar-free Mother™ at 30% (Sugar-free group), Coca Cola™ at 30% (Coke group) for a total intervention period of 13 weeks. Results: After 13 weeks of intervention, the control mice showed a modest increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) by 7.1 ± 8.8, 5.8 ± 9.4, and 6.3 ± 9.1 mmHg, respectively. However, the Energy Drink significantly decreased the DBP and MAP by 18.8 ± 9.9 and 15.3 ± 9.8 mmHg, respectively. Similarly, Sugar-free group mice showed significant decrease of the SBP, DBP, and MAP by 10.85 ± 5.6, 18.7 ± 6.7, and 15.6 ± 6.1 mmHg, respectively. The SBP, DBP, and MAP in Coke mice showed no significant changes. The estimated cumulative intake of caffeine, taurine, and vitamin B3 and B5 was significantly higher in the mice of Energy Drink and Sugar-free groups compared to the Control and Coke mice. Conclusion: Collectively, the data suggest that the long-term chronic consumption of energy drinks may significantly lower the BP in normotensive mice through the actions of caffeine, taurine, and/or B-vitamins. The study findings do not support consideration of energy drinks for BP management, but rather demonstrate no long-term amplification of BP in normotensive preclinical models. KEYWORDS: blood pressure; caffeine; coke; energy drink; sugar free energy drink; taurine; vitamin B
  15. AlPater

    Al's CR updates

    Change in self-efficacy, eating behaviors and food cravings during two years of calorie restriction in humans without obesity. Dorling J, Bhapkar M, Das SK, Racette SB, Apolzan JW, Fearnbach SN, Redman LM, Myers CA, Stewart TM, Martin CK; CALERIE Study Group. Appetite. 2019 Aug 6:104397. doi: 10.1016/j.appet.2019.104397. [Epub ahead of print] PMID: 31398376 Abstract Calorie restriction (CR) enhances longevity in humans who are normal weight, overweight and obese. While dietary regimens can change self-efficacy, eating behaviors, and food cravings in individuals with obesity, the responses of these measures to prolonged CR in individuals who are exclusively not obese is unknown. The aim of this analysis was to test the effects of a two-year CR intervention on self-efficacy and eating attitudes and behaviors in humans without obesity by analyzing data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study. Participants (n = 218, BMI range = 21.3-29.0 kg/m2) were randomized to a 25% CR group or an ad libitum (AL) group. Eating attitudes and behaviors and self-efficacy were assessed using validated questionnaires at baseline, 12, and 24 months. Dietary restraint and self-efficacy increased in the CR compared to the AL group (ES ≥ 0.32). Increased self-efficacy was negatively related to weight change (ρ < -0.24). In the CR group, males showed a reduction in cravings for carbohydrates and fats at month 24, whereas females did not. The CR group showed elevations in state hunger, which were transient, and disinhibited eating (ES ≥ 0.37). In individuals without obesity, dietary restraint and self-efficacy could be important in promoting long-term CR for individuals looking to use CR as a tool to improve longevity. KEYWORDS: Calorie restriction; Eating behaviors; Food cravings; Self-efficacy Impact of energy turnover on the regulation of glucose homeostasis in healthy subjects. Büsing F, Hägele FA, Nas A, Hasler M, Müller MJ, Bosy-Westphal A. Nutr Diabetes. 2019 Aug 8;9(1):22. doi: 10.1038/s41387-019-0089-6. PMID: 31395858 https://www.nature.com/articles/s41387-019-0089-6.pdf Abstract OBJECTIVE: Sedentary lifestyle increases the risk of type 2 diabetes. The aim of this study was to investigate the impact of different levels of energy turnover (ET; low, medium, and high level of physical activity and the corresponding energy intake) on glucose metabolism at zero energy balance, caloric restriction, and overfeeding. METHODS: Sixteen healthy individuals (13 men, 3 women, 25.1 ± 3.9 years, BMI 24.0 ± 3.2 kg/m2) participated in a randomized crossover intervention under metabolic ward conditions. Subjects passed 3 × 3 intervention days. Three levels of physical activity (PAL: low 1.3, medium 1.6, and high 1.8 achieved by walking at 4 km/h for 0, 3 × 55, or 3 × 110 min) were compared under three levels of energy balance (zero energy balance (EB): 100% of energy requirement (Ereq); caloric restriction (CR): 75% Ereq, and overfeeding (OF): 125% Ereq). Continuous interstitial glucose monitoring, C-peptide excretion, and HOMA-IR, as well as postprandial glucose and insulin were measured. RESULTS: Daylong glycemia and insulin secretion did not increase with higher ET at all conditions of energy balance (EB, CR, and OF), despite a correspondingly higher CHO intake (Δ low vs. high ET: +86 to 135 g of CHO/d). At CR, daylong glycemia (p = 0.02) and insulin secretion (p = 0.04) were even reduced with high compared with low ET. HOMA-IR was impaired with OF and improved with CR, whereas ET had no effect on fasting insulin sensitivity. A higher ET led to lower postprandial glucose and insulin levels under conditions of CR and OF. CONCLUSION: Low-intensity physical activity can significantly improve postprandial glycemic response of healthy individuals, independent of energy balance.