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  1. Association of dietary glycaemic index, glycaemic load, and total carbohydrates with incidence of type-2 diabetes in adults aged ≥40 years: The Multi-Rural Communities Cohort (MRCohort). Young Kim S, Won Woo H, Lee YH, Hoon Shin D, Shin MH, Youl Choi B, Kyung Kim M. Diabetes Res Clin Pract. 2020 Jan 14:108007. doi: 10.1016/j.diabres.2020.108007. [Epub ahead of print] PMID: 31953108 https://sci-hub.tw/https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(19)31185-4/fulltext Abstract AIMS: To examine potential associations between the glycaemic index (GI), glycaemic load (GL), and carbohydrates and the incidence risk of type-2 diabetes (T2D) and the effect modification of obesity among Korean adults aged ≥40 years. METHOD: Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2D were estimated in 8,310 participants using a modified Poisson regression model. Dietary indices were averaged using repeated dietary assessments during follow-up. RESULT: After adjusting for potential confounders, a positive association between GI and T2D was found among women (IRR=1.63, 95% CI=1.06-2.51 in the highest tertile (T3) vs. the lowest tertile (T1) for GI, p trend=0.0310), but not for GL and carbohydrate intake. This positive association with GI was stronger in obese women (IRR=1.91, 95% CI: 1.15-3.19 in T3 vs. T1, p trend=0.0137 for body mass index ≥ 23 kg/m2; IRR=2.35, 95% CI: 1.01-5.48, p trend=0.0350 for waist circumference (WC) ≥ 85 cm). In men, there was no association before stratification by obesity, but IRRs of GI (T3 vs. T1) were significant and stronger with increased WCs (IRR=2.26, 95% CI: 1.02-4.98, p trend=0.0439 for WC ≥90). CONCLUSION: GI may be positively associated with the incidence of T2D in women, particularly in obese women. The association of GI with T2D incidence risk may also be positive even in men with high WC. KEYWORDS: Carbohydrates; Glycaemic index; Glycaemic load; Prospective cohort study; Type 2 diabetes Physical Activity Compared to Adiposity and Risk of Liver-Related Mortality: Results from Two Prospective, Nationwide Cohorts. Simon TG, Kim MN, Luo X, Yang W, Ma Y, Chong DQ, Fuchs CS, Meyerhardt JA, Corey KE, Chung RT, Stampfer M, Zhang X, Giovannucci EL, Chan AT. J Hepatol. 2020 Jan 15. pii: S0168-8278(20)30013-1. doi: 10.1016/j.jhep.2019.12.022. [Epub ahead of print] PMID: 31954204 Abstract BACKGROUND & AIMS: Obesity in adulthood has been associated with increased risk of liver-related mortality. Whether higher levels of physical activity counteract the excess risk conferred by obesity remains unknown. We simultaneously evaluated the long-term impact of physical activity and adiposity on liver-related mortality, within two nationwide populations. METHODS: We conducted a prospective cohort study of 77,238 women and 48,026 men, with detailed, validated assessments of weekly physical activity (metabolic equivalent task [MET]-hours]), adiposity (body mass index [BMI], waist circumference), and diet, alcohol use and clinical comorbidities, biennially from 1986 through 2012. Using Cox proportional hazards regression models, we calculated multivariable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for liver-related mortality, including death from hepatocellular carcinoma (HCC) and other cirrhosis complications. RESULTS: Over 1,856,226 person-years, we recorded 295 liver-related deaths (108 HCC; 187 cirrhosis). Risk of liver-related mortality increased monotonically with higher BMI during adulthood (Ptrend<0.0001) and with weight gain during early-adulthood (Ptrend<0.0001). The risk of liver-related mortality also declined progressively, with increasing physical activity (Ptrend=0.0003); the aHRs across increasing physical activity quintiles were: 1.0, 0.70 (95%CI=0.51-0.96), 0.59 (95%CI=0.42-0.84), 0.52 (95%CI=0.36-0.74) and 0.46 (95%CI=0.31-0.66). Compared to lean-active adults (BMI<25; ≥18 MET-hours/week), the aHRs for obese-active, lean-sedentary, and obese-sedentary adults were: 1.04 (95%CI=0.73-1.37), 2.08 (95%CI=1.21-3.33) and 3.40 (95%CI=2.06-5.56), respectively. Findings were similar for HCC-specific and cirrhosis-specific mortality. Overall, engaging in average-pace walking for >3 hours/week could have prevented 25% of liver-related deaths (95%CI=0.12-0.38). CONCLUSIONS: In two prospective, nationwide cohorts, both excess adiposity and reduced PA were significant predictors of liver-related mortality. Achieving higher PA levels counteracted the excess liver-related risks associated with obesity. KEYWORDS: cirrhosis; lifestyle; modifiable risk factor; prevention The relationship between consumption of nitrite or nitrate and risk of non-Hodgkin lymphoma. Yu M, Li C, Hu C, Jin J, Qian S, Jin J. Sci Rep. 2020 Jan 17;10(1):551. doi: 10.1038/s41598-020-57453-5. PMID: 31953513 Abstract Epidemiologic studies of the relationship between nitrite or nitrate consumption and risk of non-Hodgkin lymphoma (NHL) remain controversial. The current meta-analysis aimed to reexamine the evidence and quantitatively evaluate that relationship. Manuscripts were retrieved from the Web of Science, Chinese National Knowledge Infrastructure and PubMed databases up to May 2019. From the studies included in the review, results were combined and presented as odds ratios (OR). To conduct a dose-response (DR) analysis, studies presenting risk estimates over a series of categories of exposure were selected. Our data indicate that the consumption of nitrite was linked to a significantly increased hazard of NHL (OR: 1.37; 95% CI: 1.14-1.65), rather than nitrate (OR: 1.02; 95% CI: 0.94-1.10). According to Egger's and Begg's tests (P > 0.05), there was no evidence of significant publication bias. Moreover, our DR analysis indicated that the risk of NHL grew by 26% for each additional microgram of nitrite consumed in the diet per day (OR: 1.26; 95% CI: 1.09-1.42). Through subset analysis of the nitrite studies, data from the high-quality studies indicated that consumption was positively associated with carcinogenicity, leading to NHL (OR: 1.44; 95% CI: 1.17-1.77) and positively correlated with the development of diffuse large B-cell lymphoma (OR: 1.55; 95% CI: 1.07-2.26), but not other NHL subtypes. In addition, the data suggested that females (OR: 1.50; 95% CI: 1.15-1.95) and high levels of nitrite intake (OR: 1.64; 95% CI: 1.28-2.09) had a higher risk of NHL. Our meta-analysis supports the hypothesis that nitrite intake, but not that of nitrate, raises the risk of developing NHL. In the future, better designed prospective research studies should be conducted to confirm our findings, clarify potential biological mechanisms and instruct clinicians about NHL prophylaxis. Red Cell Distribution Width Is Directly Associated with Poor Cognitive Performance among Nonanemic, Middle-Aged, Urban Adults. Beydoun MA, Hossain S, Beydoun HA, Shaked D, Weiss J, Evans MK, Zonderman AB. J Nutr. 2020 Jan 1;150(1):128-139. doi: 10.1093/jn/nxz182. PMID: 31912144 https://watermark.silverchair.com/nxz182.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlQwggJQBgkqhkiG9w0BBwagggJBMIICPQIBADCCAjYGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2w8Uzw19FIgDKgLEAgEQgIICB2ulZd0jP61koX9hfWrJhwnEJLHLAsOW9JWnf_sZPQI87JuoRORbgtOK6b8My8ojlRDqsTKa1zhFW2JlZlw6SU5kG_KVPLCRiWJTA1Tw1KkMTK26sqWeA3ruBeDXxTheqDMG1vt7HKTrxvLzmToHAl6hcTn8ym7jcSFypUUbxxN0XttsDYboP3D8_yjAvfxrvJ7g35C4FC5e0rPkglv2Xy0C09AfbG3Ciif1xdA4ZZVstJ2iUDSte9ZzfyOhpuNMjhSXcVUlUlQ6qhFfFFC2-GZ7POU8sXiz_4LbN7Bg0AFiSvPiL7SaKOnv47vafj4vhRD-isHAaiORrEObsD2OUUeOoxG9FEy_bLBOXeaweYAkY1z-fh3Gq5yPUTZxUObkzYEiLNOr7GC1TyV-_0slQc1jhVdQAA9--S1-M-vaM2CzspCNHJkN1mMu_tuEUnYaw_sAu0RDAwBR39b75mpXAqZkYHW_TPhPRIb5AFGGUzwrSKZb7PbXmxYIxmzSl2MD7KE4teulJ68ecZqFnKGy68OJbnB2VCFPQmOydc7_VHmt918a97fSuc-m8KCoNTQ6dmE0CQQjzqsRN4yFJxdbenUec9kVoW39dZDFrn04hG8ENUxRK6VItr1FwzDNr_gfEF3tHbvOqw70JMnm4PWK07qR3gWUwZyku20tVW2EyxwDi4rWQMyfDQ Abstract BACKGROUND: Epidemiological evidence suggests that both anemia and elevated red cell distribution width (RDW) are associated with cognitive impairment. However, the interplay between these 2 predictors has been understudied. OBJECTIVES: We examined sex- and anemia-specific associations between RDW and cognitive performance among urban adults in the United States. METHODS: Data from the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study (Baltimore, MD; participants aged 30-65 y at baseline, ∼59% African-American, 45% men) were used. Participants were selected based on the completion of 11 cognitive tasks at baseline (2004-2009) and follow-up (2009-2013) visits (mean time between visits: 4.64 ± 0.93 y) and availability of exposure and covariate data, yielding a sample of between 1526 and 1646 adults out of the initial 3720 adults recruited at baseline. Multiple linear mixed-effects regression models were conducted with RDW as the main exposure of interest and anemia/sex as the key effect modifiers. RESULTS: Overall, high RDWs were linked to poorer baseline performance on the California Verbal Learning Test (CVLT) List A (per 1 unit increase in RDW %, main effect: γ01 = -0.369 ± 0.114; P = 0.001) and to slower rates of decline on the CVLT Delayed Free Recall (per 1 unit increase in RDW %, RDW × time: γ11 = +0.036 ± 0.013; P = 0.007). Among nonanemic participants, RDWs were consistently associated with poorer baseline performance on the Trailmaking Test, Part A (γ01 = +3.11 ± 0.89; P < 0.001) and on the CVLT List A (γ01 = -0.560 ± 0.158; P < 0.001). Moreover, RDWs were associated with poorer baseline performance on the Brief Test of Attention in the total population (γ01 = -0.123 ± 0.039; P = 0.001) and among men (γ01 = -0.221 ± 0.068; P = 0.001). We did not detect an association between hemoglobin (Hb) and baseline cognitive performance or changes over time. CONCLUSIONS: Elevated RDW had a consistent cross-sectional association with poor cognitive performance in the domains of verbal memory and attention among the nonanemic group in a sample of middle-aged, urban adults. Anemia and Hb concentrations were not associated with cognition. More longitudinal studies are needed to replicate our findings. KEYWORDS: anemia; cognitive performance; red cell distribution width; urban adults; aging Carbohydrate-restricted diet alters the gut microbiota, promotes senescence and shortens the life span in senescence-accelerated prone mice. He C, Wu Q, Hayashi N, Nakano F, Nakatsukasa E, Tsuduki T. J Nutr Biochem. 2019 Dec 20;78:108326. doi: 10.1016/j.jnutbio.2019.108326. [Epub ahead of print] PMID: 31952014 Abstract This study examined the effects of a carbohydrate-restricted diet on aging, brain function, intestinal bacteria and the life span to determine long-term carbohydrate-restriction effects on the aging process in senescence-accelerated prone mice (SAMP8). Three-week-old male SAMP8 were divided into three groups after a week of preliminary feeding. One group was given a controlled diet, while the others fed on high-fat and carbohydrate-restricted diets, respectively. The mice in each group were further divided into two subgroups, of which one was the longevity measurement group. The other groups fed ad libitum until the mice were 50 weeks old. Before the test period termination, passive avoidance test evaluated the learning and memory abilities. Following the test period, serum and various mice organs were obtained and submitted for analysis. The carbohydrate-restricted diet group exhibited significant decrease in the survival rate as compared to the other two diet groups. The passive avoidance test revealed a remarkable decrease in the learning and memory ability of carbohydrate-restricted diet group as compared to the control-diet group. Measurement of lipid peroxide level in tissues displayed a marked increase in the brain and spleen of carbohydrate-restricted diet group than the control-diet and high-fat diet groups. Furthermore, notable serum IL-6 and IL-1β level (inflammation indicators) elevations, decrease in Enterobacteria (with anti-inflammatory action), increase in inflammation-inducing Enterobacteria and lowering of short-chain fatty acids levels in cecum were observed in the carbohydrate-restricted diet group. Hence, carbohydrate-restricted diet was revealed to promote aging and shortening of life in SAMP8. KEYWORDS: Aging; Carbohydrate-restricted diet; Gut microbiota; Senescence-accelerated mice; Short-chain fatty acids Association between breastfeeding and osteoporotic hip fracture in women: a dose-response meta-analysis. Xiao H, Zhou Q, Niu G, Han G, Zhang Z, Zhang Q, Bai J, Zhu X. J Orthop Surg Res. 2020 Jan 16;15(1):15. doi: 10.1186/s13018-019-1541-y. PMID: 31948457 Abstract OBJECTIVE: Approximately 300 mg of calcium a day is provided into infants to maintain the physical development of infants, and 5 to 10% bone loss occurs in women during breastfeeding. Hip fractures are considered the most serious type of osteoporotic fracture. We performed this meta-analysis to investigate the association between breastfeeding and osteoporotic hip fractures. MATERIAL AND METHODS: PubMed and Embase were searched until May 1, 2019, for studies evaluating the relationship between breastfeeding and osteoporotic hip fracture in women. The quality of the included studies was evaluated by the methodological index for non-randomized studies (MINORS). For the dose-response meta-analysis, we used the "generalized least squares for trend estimation" method proposed by Greenland and Longnecker to take into account the correlation with the log RR estimates across the duration of breastfeeding. RESULTS: Seven studies were moderate or high quality, enrolling a total of 103,898 subjects. The pooled outcomes suggested that breastfeeding can decrease the incidence of osteoporotic hip fracture (RR = 0.64 (95% CI 0.43, 0.95), P = 0.027). Dose-response analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the increase of breastfeeding time. The RR and 95% CI for 3 months, 6 months, 12 months, and 24 months were RR = 0.93, 95% CI 0.88, 0.98; RR = 0.87, 95% CI 0.79, 0.96; RR = 0.79, 95% CI 0.67, 0.92; and RR = 0.76, 95% CI 0.59, 0.98, respectively, whereas no significant relationship was found between them when the duration of breastfeeding time was more than 25 months. CONCLUSIONS: Our meta-analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the extension of breastfeeding time. However, there is no significant relationship between them when the duration of breastfeeding time was more than 25 months. KEYWORDS: Breast feeding; Hip fractures; Meta-analysis
  2. AlPater

    Al's CR updates

    Deletion of Nrf2 shortens lifespan in C57BL6/J male mice but does not alter the health and survival benefits of caloric restriction. Pomatto LCD, Dill T, Carboneau B, Levan S, Kato J, Mercken EM, Pearson KJ, Bernier M, de Cabo R. Free Radic Biol Med. 2020 Jan 14. pii: S0891-5849(19)32365-2. doi: 10.1016/j.freeradbiomed.2020.01.005. [Epub ahead of print] PMID: 31953150 https://sci-hub.tw/10.1016/j.freeradbiomed.2020.01.005 Abstract Caloric restriction (CR) is the leading non-pharmaceutical dietary intervention to improve health- and lifespan in most model organisms. A wide array of cellular pathways is induced in response to CR and CR-mimetics, including the transcriptional activator Nuclear factor erythroid-2-related factor 2 (Nrf2), which is essential in the upregulation of multiple stress-responsive and mitochondrial enzymes. Nrf2 is necessary in tumor protection but is not essential for the lifespan extending properties of CR in outbred mice. Here, we sought to study Nrf2-knockout (KO) mice and littermate controls in male C57BL6/J, an inbred mouse strain. Deletion of Nrf2 resulted in shortened lifespan compared to littermate controls only under ad libitum conditions. CR-mediated lifespan extension and physical performance improvements did not require Nrf2. Metabolic and protein homeostasis and activation of tissue-specific cytoprotective proteins were dependent on Nrf2 expression. These results highlight an important contribution of Nrf2 for normal lifespan and stress response.
  3. Dietary glycemic index and glycemic load during pregnancy and offspring risk of congenital heart defects: a prospective cohort study. Schmidt AB, Lund M, Corn G, Halldorsson TI, Øyen N, Wohlfahrt J, Olsen SF, Melbye M. Am J Clin Nutr. 2020 Jan 14. pii: nqz342. doi: 10.1093/ajcn/nqz342. [Epub ahead of print] PMID: 31942930 Abstract BACKGROUND: Prepregnancy diabetes, especially when severely dysregulated, is associated with an increased risk of congenital heart defects in offspring. This suggests that glucose plays a role in embryonic heart development. OBJECTIVE: The aim was to investigate the association between midpregnancy dietary glycemic index (GI), glycemic load (GL), and sugar-sweetened beverages and the risk of congenital heart defects in the offspring. METHODS: Offspring of mothers from the Danish National Birth Cohort who filled out a food-frequency questionnaire (FFQ) covering midpregnancy dietary intake were included. Individual-level information on GI and GL, offspring congenital heart defects, and health and lifestyle covariates was linked. The association between GI and GL and offspring congenital heart defects was estimated by logistic regression. Further, we evaluated whether maternal intake of sugar-sweetened drinks increased the risk of offspring congenital heart defects. RESULTS: In total, 66,387 offspring of women who responded to the FFQ were included; among offspring, 543 had a congenital heart defect. The adjusted OR (aOR) of congenital heart defects among offspring of mothers belonging to the highest versus the lowest GI quintile was 1.02 (95% CI: 0.78, 1.34; P-trend = 0.86). Results were similar for GL (aOR: 0.95; 95% CI: 0.72, 1.24). A high intake of sugar-sweetened carbonated beverages was associated with a statistically significant increased risk of offspring congenital heart defects (highest vs lowest intake-aOR: 2.41; 95% CI: 1.26, 4.64; P-trend = 0.03). No association was found with other types of beverages. CONCLUSIONS: The study does not support an association between a high GI and GL in midpregnancy and increased offspring risk of congenital heart defects. Nevertheless, a statistically significant association between sugar-sweetened carbonated beverages and a moderately increased risk of offspring congenital heart defects was observed. KEYWORDS: Danish National Birth Cohort; congenital heart defects; food-frequency questionnaire; glycemic index; glycemic load; pregnancy; sugar-sweetened beverages Dietary Phospholipids: Role in Cognitive Processes Across the Lifespan. Schverer M, O'Mahony SM, O'Riordan KJ, Donoso F, Roy BL, Stanton C, Dinan TG, Schellekens H, Cryan JF. Neurosci Biobehav Rev. 2020 Jan 13. pii: S0149-7634(19)31034-6. doi: 10.1016/j.neubiorev.2020.01.012. [Epub ahead of print] Review. PMID: 31945391 https://sci-hub.tw/10.1016/j.neubiorev.2020.01.012 Abstract Chronic stress and ageing are two of the most important factors that negatively affect cognitive processes such as learning and memory across the lifespan. To date, pharmacological agents have been insufficient in reducing the impact of both on brain health, and thus, novel therapeutic strategies are required. Recent research has focused on nutritional interventions to modify behaviour and reduce the deleterious consequences of both stress and ageing. In this context, emerging evidence indicate that phospholipids, a specific type of fat, are capable of improving a variety of cognitive processes in both animals and humans. The mechanisms underlying these positive effects are actively being investigated but as of yet are not fully elucidated. In this review, we summarise the preclinical and clinical studies available on phospholipid-based strategies for improved brain health across the lifespan. Moreover, we summarize the hypothesized direct and indirect mechanisms of action of these lipid-based interventions which may be used to promote resilience to stress and improve age-related cognitive decline in vulnerable populations. KEYWORDS: ageing; brain health; cognition; dietary phospholipids; gut; microbiota; stress Low-fat dietary pattern and global cognitive function: Exploratory analyses of the Women's Health Initiative (WHI) randomized Dietary Modification trial. Chlebowski RT, Rapp S, Aragaki AK, Pan K, Neuhouser ML, Snetselaar LG, Manson JE, Wactawski-Wende J, Johnson KC, Hayden K, Baker LD, Henderson VW, Garcia L, Qi L, Prentice RL. EClinicalMedicine. 2020 Jan 8;18:100240. doi: 10.1016/j.eclinm.2019.100240. eCollection 2020 Jan. PMID: 31938786 Abstract BACKGROUND: Meta-analyses of observational studies associate adherence to several dietary patterns with cognitive health. However, limited evidence from full scale, randomized controlled trials precludes causal inference regarding dietary effects on cognitive function. METHODS: The Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, in 48,835 postmenopausal women, included a subset of 1,606 WHI Memory Study (WHIMS) participants >= 65 years old, to assess low-fat dietary pattern influence on global cognitive function, evaluated with annual screening (Modified Mini-Mental State Examinations [3MSE]). Participants were randomized by a computerized, permuted block algorithm, stratified by age group and center, to a dietary intervention (40%) to reduce fat intake to 20% of energy and increase fruit, vegetable and grain intake or usual diet comparison groups (60%). The study outcome was possible cognition impairment (failed cognitive function screening) through the 8.5 year (median) dietary intervention. Those failing screening received a comprehensive, multi-phase cognitive function assessment to classify as: no cognitive impairment, mild cognitive impairment, or probable dementia. Exploratory analyses examined the composite endpoint of death after possible cognitive impairment through 18.7 years (median) follow-up. The WHI trials are registered at ClinicalTrials.gov:NCT00000611. FINDINGS: Among the 1,606 WHIMS participants, the dietary intervention statistically significantly reduced the incidence of possible cognitive impairment (n = 126; hazard ratio 0.59 95% confidence interval [CI] 0.38-0. 91, P = 0.01) with HR for dietary influence on subsequent mild cognitive impairment of 0.65 (95% CI 0.35-1.19) and HR of 0.63 (95% CI 0.19-2.10) for probable dementia (PD). Through 18.7 years, deaths from all-causes after possible cognitive impairment were non-significantly lower in the dietary intervention group (0.56% vs 0.77%, HR 0.83 95% CI 0.35 to 2.00, P = 0.16). INTERPRETATION: Adoption of a low-fat eating pattern, representing dietary moderation, significantly reduced risk of possible cognitive impairment in postmenopausal women. KEYWORDS: Cognition; Dietary modification; Low-fat dietary pattern; Randomized clinical trial; Women's Health Initiative Food consumption and depression among Brazilian adults: results from the Brazilian National Health Survey, 2013. Sousa KT, Marques ES, Levy RB, Azeredo CM. Cad Saude Publica. 2019 Dec 20;36(1):e00245818. doi: 10.1590/0102-311X00245818. eCollection 2019. PMID: 31939555 Abstract Our study aimed to evaluate the association between food consumption and depression. We used data from the Brazilian National Health Survey; a cross-sectional study carried out in 2013 among 46,785 Brazilian adults. The exposures were regular consumption (≥ 5 times/week) of the markers of healthy (beans, vegetables, fruits, and natural fruit juices) and unhealthy food (sugar sweetened beverages; sweets and the substitution of lunch or dinner for snacks); and a nutritional score elaborated by combining the frequency of consumption of markers of healthy and unhealthy food, the higher the value, the better the diet. The outcome was depression, assessed through the PHQ-9 questionnaire answered by the participants. Those with PHQ-9 scores greater than or equal to 10 were classified as presenting depression. We performed logistic regression models adjusted for potential confounders. Regular consumption of sweets (OR = 1.53; 95%CI: 1.33-1.76) and regular replacement of meals for snacks (OR = 1.52; 95%CI: 1.21-1.90) were positively associated with depression. Regular consumption of sugar sweetened beverages was positively associated with depression among women (OR = 1.27; 95%CI: 1.10-1.48). Regular consumption of beans was negatively associated with depression (OR = 0.74; 95%CI: 0.65-0.84), consistent for both sexes. Comparing the top quintile of the nutritional score (healthier diet) to the bottom quintile (less healthy) we found a negative association with depression (OR = 0.63; 95%CI: 0.52-0.75). Our results add evidence on a possible role of food consumption in depression; future longitudinal studies should explore the mechanisms of these associations. Impact of intermittent vs. continuous energy restriction on weight and cardiometabolic factors: a 12-month follow-up. Headland ML, Clifton PM, Keogh JB. Int J Obes (Lond). 2020 Jan 14. doi: 10.1038/s41366-020-0525-7. [Epub ahead of print] PMID: 31937907 Abstract BACKGROUND AND OBJECTIVE: Intermittent energy restriction continues to gain popularity as a weight loss strategy; however, data assessing it's long-term viability is limited. The objective of this study was to follow up with participants 12 months after they had completed a 12-month dietary intervention trial involving continuous energy restriction and two forms of intermittent energy restriction; a week-on-week-off energy restriction and a 5:2 programme, assessing long-term changes on weight, body composition, blood lipids and glucose. SUBJECTS AND METHODS: 109 overweight and obese adults, aged 18-72 years, attended a 12-month follow-up after completing a 12-month dietary intervention involving three groups: continuous energy restriction (1000 kcal/day for women and 1200 kcal/day for men), week-on-week-off energy restriction (alternating between the same energy restriction as the continuous group for one week and one week of habitual diet), or 5:2 (500 kcal/day on modified fast days each week for women and 600 kcal/day for men). The primary outcome was weight change at 24 months from baseline, with secondary outcomes of change in body composition, blood lipids and glucose. RESULTS: For the 109 individuals who completed the 12-month follow-up (82 female, 15 male, mean BMI 33 kg/m2), weight decreased over time with no differences between week-on and week-off and continuous energy restriction or 5:2 and continuous energy restriction with -4.5 ± 4.9 kg for continuous energy restriction, -2.8 ± 6.5 kg for week-on, week-off and -3.5 ± 5.1 kg for 5:2. Total cholesterol reduced over time and glucose, HDL, LDL and triglycerides were unchanged. DISCUSSION AND CONCLUSION: Intermittent energy restriction was as successful in achieving modest weight loss over a 24-month period as continuous energy restriction.
  4. AlPater

    Al's CR updates

    Lifestyle vs. pharmacological interventions for healthy aging. Furrer R, Handschin C. Aging (Albany NY). 2020 Jan 10:5-7. doi: 10.18632/aging.102741. [Epub ahead of print] No abstract available. PMID: 31937689 https://www.aging-us.com/article/102741/text KEYWORDS: aging; caloric restriction; exercise; metformin; rapamycin
  5. The 17β-oestradiol treatment minimizes the adverse effects of protein restriction on bone parameters in ovariectomized Wistar rats: Relevance to osteoporosis and the menopause. de Quadros VP, Tobar N, Viana LR, Dos Santos RW, Kiyataka PHM, Gomes-Marcondes MCC. Bone Joint Res. 2020 Jan 8;8(12):573-581. doi: 10.1302/2046-3758.812.BJR-2018-0259.R2. eCollection 2019 Dec. PMID: 31934328 https://online.boneandjoint.org.uk/doi/epub/10.1302/2046-3758.812.BJR-2018-0259.R2 Abstract OBJECTIVES: Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol. METHODS: Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17β-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy. RESULTS: The results showed that protein restriction negatively affected body chemical composition and bone metabolism by the sex hormone deficiency condition in the OVX group. The association between undernutrition and hormone deficiency led to bone and muscle mass loss and increased the fragility of the bone (as well as decreasing relative femoral weight, bone mineral density, femoral elasticity, peak stress, and stress at offset yield). Although protein restriction induced more severe adverse effects compared with the controls, the combination with HRT showed an improvement in minimizing these damaging effects, as it was seen that HRT had some efficacy in maintaining muscle and bone mass, preserving the bone resistance and minimizing some deleterious processes during the menopause. CONCLUSION: Protein restriction has adverse effects on metabolism, leading to more severe menopausal symptoms, and HRT could minimize these effects. Therefore, special attention should be given to a balanced diet during menopause and HRT.Cite this article: Bone Joint Res 2019;8:573-581. KEYWORDS: Hormone replacement therapy; Ovariectomy; Postmenopausal osteoporosis; Protein restriction; Rat Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study. Liu G, Zhang B, Hu Y, Rood J, Liang L, Qi L, Bray GA, DeJonge L, Coull B, Grandjean P, Furtado JD, Sun Q. Environ Health. 2020 Jan 13;19(1):5. doi: 10.1186/s12940-020-0561-8. PMID: 31931806 Abstract BACKGROUND: The associations of perfluoroalkyl substance (PFAS) exposure with blood lipids and lipoproteins are inconsistent, and existing studies did not account for metabolic heterogeneity of lipoprotein subspecies. This study aimed to examine the associations between plasma PFAS concentrations and lipoprotein and apolipoprotein subspecies. METHODS: The study included 326 men and women from the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) Lost randomized trial. Five PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), were measured in plasma at baseline. For lipoprotein and apolipoprotein subspecies, total plasma was fractionated first by apolipoprotein (apo) C-III content and then by density. Each subfraction was then measured for apoB, apoC-III, and apoE concentrations, as well as triglyceride and cholesterol contents, both at baseline and at 2 years. RESULTS: For lipids and apolipoproteins in total plasma at baseline, elevated plasma PFAS concentrations were significantly associated with higher apoB and apoC-III concentrations, but not with total cholesterol or triglycerides. After multivariate adjustment of lifestyle factors, lipid-lowering medication use, and dietary intervention groups, PFAS concentrations were primarily associated with lipids or apolipoprotein concentrations in intermediate-to-low density lipoprotein (IDL + LDL) and high-density lipoprotein (HDL) that contain apoC-III. Comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) were 4.16 (0.4) vs 3.47 (0.4) for apoB (P trend = 0.04), 2.03 (0.2) vs 1.66 (0.2) for apoC-III (P trend = 0.04), and 8.4 (0.8) vs 6.8 (0.8) for triglycerides (P trend = 0.03) in IDL + LDL fraction that contains apoC-III. For HDL that contains apoC-III, comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) of apoC-III were 11.9 (0.7) vs 10.4 (0.7) (P trend = 0.01). In addition, elevated PFNA and PFDA concentrations were also significantly associated with higher concentrations of apoE in HDL that contains apoC-III (P trend< 0.01). Similar patterns of associations were demonstrated between baseline PFAS concentrations and lipoprotein subspecies measured at 2 years. Baseline PFAS levels were not associated with changes in lipoprotein subspecies during the intervention. CONCLUSIONS: Our results suggest that plasma PFAS concentrations are primarily associated with blood lipids and apolipoproteins in subspecies of IDL, LDL, and HDL that contain apoC-III, which are associated with elevated cardiovascular risk in epidemiological studies. Future studies of PFAS-associated cardiovascular risk should focus on lipid subfractions. KEYWORDS: Epidemiology; Lipid subfractions; Perfluoroalkyl substance Nutrient-wide association study of 92 foods and nutrients and breast cancer risk. Heath AK, Muller DC, van den Brandt PA, Papadimitriou N, Critselis E, Gunter M, Vineis P, Weiderpass E, Fagherazzi G, Boeing H, Ferrari P, Olsen A, Tjønneland A, Arveux P, Boutron-Ruault MC, Mancini FR, Kühn T, Turzanski-Fortner R, Schulze MB, Karakatsani A, Thriskos P, Trichopoulou A, Masala G, Contiero P, Ricceri F, Panico S, Bueno-de-Mesquita B, Bakker MF, van Gils CH, Olsen KS, Skeie G, Lasheras C, Agudo A, Rodríguez-Barranco M, Sánchez MJ, Amiano P, Chirlaque MD, Barricarte A, Drake I, Ericson U, Johansson I, Winkvist A, Key T, Freisling H, His M, Huybrechts I, Christakoudi S, Ellingjord-Dale M, Riboli E, Tsilidis KK, Tzoulaki I. Breast Cancer Res. 2020 Jan 13;22(1):5. doi: 10.1186/s13058-019-1244-7. PMID: 31931881 https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/s13058-019-1244-7 Abstract BACKGROUND: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. METHODS: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). RESULTS: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. CONCLUSIONS: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk. KEYWORDS: Alcohol; Breast cancer; Diet; Fibre; Foods; Nutrients Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort. Gentiluomo M, Katzke VA, Kaaks R, Tjonneland A, Severi G, Perduca V, Boutron-Ruault MC, Weiderpass E, Ferrari P, Johnson T, Schulze MB, Bergmann M, Trichopoulou A, Karakatsani A, La Vecchia C, Palli D, Grioni S, Panico S, Tumino R, Sacerdote C, Bueno-de-Mesquita B, Vermeulen R, Sandanger TM, Quirós JR, Rodríguez-Barranco M, Amiano P, Colorado-Yohar S, Ardanaz E, Sund M, Khaw KT, Wareham NJ, Schmidt JA, Jakszyn P, Morelli L, Canzian F, Campa D. Cancer Epidemiol Biomarkers Prev. 2020 Jan 13. pii: cebp.0868.2019. doi: 10.1158/1055-9965.EPI-19-0868. [Epub ahead of print] PMID: 31932413 Abstract BACKGROUND: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. METHODS: To further our knowledge on this topic we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. RESULTS: We observed lower mtDNA copy number with advancing age (p=6.54×10-5) and with a high BMI level (p=0.004) and no association with sex, smoking behavior and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an OR=0.35 (95% C.I 0.16-0.79), p=0.01 when comparing the 5th quintile with the 1st using an unconditional logistic regression and OR=0.19 (95% C.I 0.07-0.52), p=0.001 with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. CONCLUSIONS: Our results, suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. IMPACT: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer. The effects of low-carbohydrate diets on cardiovascular risk factors: A meta-analysis. Dong T, Guo M, Zhang P, Sun G, Chen B. PLoS One. 2020 Jan 14;15(1):e0225348. doi: 10.1371/journal.pone.0225348. eCollection 2020. PMID: 31935216 Abstract BACKGROUND: Low-carbohydrate diets are associated with cardiovascular risk factors; however, the results of different studies are inconsistent. PURPOSE: The aim of this meta-analysis was to assess the relationship between low-carbohydrate diets and cardiovascular risk factors. METHOD: Four electronic databases (PubMed, Embase, Medline, and the Cochrane Library) were searched from their inception to November 2018. We collected data from 12 randomized trials on low-carbohydrate diets including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, and blood pressure levels, as well as weight as the endpoints. The average difference (MD) was used as the index to measure the effect of a low-carbohydrate diet on cardiovascular risk factors with a fixed-effects model or random-effects model. The analysis was further stratified by factors that might affect the results of the intervention. RESULTS: From 1292 studies identified in the initial search results, 12 randomized studies were included in the final analysis, which showed that a low-carbohydrate diet was associated with a decrease in triglyceride levels of -0.15mmol/l (95% confidence interval -0.23 to -0.07). Low-carbohydrate diet interventions lasting less than 6 months were associated with a decrease of -0.23mmol/l (95% confidence interval -0.32 to -0.15), while those lasting 12-23 months were associated with a decrease of -0.17mmol/l (95% confidence interval -0.32 to -0.01). The change in the body weight in the observation groups was -1.58kg (95% confidence interval -1.58 to -0.75); with for less than 6 months of intervention,this change was -1.14 kg (95% confidence interval -1.65 to -0.63),and with for 6-11 months of intervention, this change was -1.73kg (95% confidence interval -2.7 to -0.76). The change in the systolic blood pressure of the observation group was -1.41mmHg (95% confidence interval-2.26 to -0.56); the change in diastolic blood pressure was -1.71mmHg (95% confidence interval-2.36 to -1.06); the change in plasma HDL-C levels was 0.1mmHg (95% confidence interval 0.08 to 0.12); and the change in serum total cholesterol was 0.13mmol/l (95% confidence interval 0.08 to 0.19). The plasma LDL-C level increased by 0.11mmol/l (95% confidence interval 0.02 to 0.19), and the fasting blood glucose level changed 0.03mmol/l (95% confidence interval -0.05 to 0.12),which was not significant. CONCLUSIONS: This meta-analysis confirms that low-carbohydrate diets have a beneficial effect on cardiovascular risk factors but that the long-term effects on cardiovascular risk factors require further research.
  6. Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease. Lazic D, Tesic V, Jovanovic M, Brkic M, Milanovic D, Zlokovic BV, Kanazir S, Perovic M. Neurobiol Dis. 2020 Jan 10:104745. doi: 10.1016/j.nbd.2020.104745. [Epub ahead of print] PMID: 31931140 https://www.sciencedirect.com/science/article/pii/S0969996120300206?via%3Dihub Abstract Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing the importance of the type, onset and duration of food restriction. In the present study, we assessed the effects of preventive every-other-day (EOD) feeding regimen on neurodegenerative phenotype in 5XFAD transgenic mice, a commonly used mouse model of Alzheimer's disease. EOD feeding regimen was introduced to transgenic female mice at the age of 2 months and the effects on amyloid-β (Aβ) accumulation, gliosis, synaptic plasticity, and blood-brain barrier breakdown were analyzed in cortical tissue of 6-month-old animals. Surprisingly, significant increase of inflammation in the cortex of 5XFAD fed EOD mice was observed, reflected by the expression of microglial and astrocytic markers. This increase in reactivity and/or proliferation of glial cells was accompanied by an increase in proinflammatory cytokine TNF-α, p38 MAPK and EAAT2, and a decrease in GAD67. NMDA receptor subunit 2B, related to glutamate excitotoxicity, was increased in the cortex of 5XFAD-EOD mice indicating additional alterations in glutamatergic signaling. Furthermore, 4 months of EOD feeding regimen had led to synaptic plasticity proteins reduction and neuronal injury in 5XFAD mice. However, EOD feeding regimen did not affect Aβ load and blood-brain barrier permeability in the cortex of 5XFAD mice. Our results demonstrate that EOD feeding regimen exacerbates Alzheimer's disease-like neurodegenerative and neuroinflammatory changes irrespective of Aβ pathology in 5XFAD mice, suggesting that caution should be paid when using food restrictions in the prodromal phase of this neurodegenerative disease. KEYWORDS: 5XFAD; Alzheimer's disease; EOD dietary restriction; Inflammation; Intermittent fasting; Neuritic dystrophy; Synaptic plasticity A blood test that predicts the risk of dying Dr. Brian Goldman · CBC News · Posted: Jan 13, 2020 https://www.cbc.ca/radio/whitecoat/a-blood-test-that-predicts-the-risk-of-dying-1.5424633 Incidental lymphopenia and mortality: a prospective cohort study Marie Warny, Jens Helby, Børge Grønne Nordestgaard, Henrik Birgens and Stig Egil Bojesen CMAJ January 13, 2020 192 (2) E25-E33; DOI: https://doi.org/10.1503/cmaj.191024 Abstract BACKGROUND: It is unknown if incidental lymphopenia detected in the general population is associated with higher all-cause and cause-specific mortality. We aimed to identify the associations between lymphopenia and all-cause and cause specific mortality. METHODS: In a prospective cohort study, we examined and followed participants enrolled in the Copenhagen General Population Study between November 2003 and April 2015. In our analysis, we modelled risks using Cox proportional hazards regression for 3 groups: participants with a lymphocyte count below the 2.5th percentile; those with a lymphocyte count at or between the 2.5th and 97.5th percentiles (reference category); and those with a lymphocyte count above the 97.5th percentile. RESULTS: The cohort included 108 135 participants with a median age of 68 years. During a median follow-up of 9 (interquartile range [IQR] 0–14) years, 10 372 participants died. We found that participants with lymphopenia (lymphocyte count < 1.1 × 109/L) compared with those with a lymphocyte count in the reference range (1.1–3.7 × 109/L) had higher mortality with multivariable adjusted hazard ratios (HRs) of 1.63 (95% confidence interval [CI] 1.51–1.76) for all causes, 1.67 (95% CI 1.42–1.97) for nonhematologic cancers, 2.79 (95% CI 1.82–4.28) for hematologic cancers, 1.88 (95% CI 1.61–2.20) for cardiovascular diseases, 1.88 (95% CI 1.55–2.29) for respiratory diseases, 1.86 (95% CI 1.53–2.25) for infectious diseases, and 1.50 (95% CI 1.19–1.88) for other causes. For all-cause mortality, the highest absolute 2-year risks of death were observed in women (61%) and men (75%) who smoked and were aged 80 years or older with lymphocyte counts less than 0.5 × 109/L. Participants with a lymphocyte count higher than the reference category had increased mortality (adjusted HR 1.17, 95% CI 1.04–1.31). INTERPRETATION: We found that lymphopenia was associated with an increased risk of all-cause and cause-specific mortality. Jeanne Calment's unique 122-year lifespan: facts and factors; longevity history in her genealogical tree. Robin-Champigneul F. Rejuvenation Res. 2020 Jan 13. doi: 10.1089/rej.2019.2298. [Epub ahead of print] PMID: 31928146 https://sci-hub.tw/10.1089/rej.2019.2298 Abstract Jeanne Calment's (JC) still unmatched validated human lifespan of 122 years and 164 days, over 3 years longer than any other, surprises many. While her case is broadly accepted as a golden standard of validation, her record age still raises skepticism among some. The probability of such a record to be achieved by someone born in the second half of the 19th century, in the world population documentarily eligible to age validation, and also in the G7 countries, can be calculated by applying some logistic and Gompertz mortality models to these populations, taken respectively from the age of 117 and of 100. This probability appears substantial, respectively 7.1% and 4.7%, when using a 4-parameters logistic model which I validated on the observed survivals of centenarians until the age of 118. A 3-year interval with the second oldest is then expected. The known facts and documents constitute consistent evidence that JC died at 122: regular official records during her life, her verified memories from her 19th-century life, her usage of specialized terms and of an abbreviation system specific to this period of time, photos, her signature and handwriting, testimonies from numerous witnesses of her life, plus the expertise of gerontologists. Meanwhile, nothing contradicts her record: the daughter-mother identity swap hypothesis appears unrealistic and not supported by any evidence; especially no plausible motive can be found, on the contrary. The latest paper which defends this hypothesis, "Bayesian assessment of the longevity of JC", contains major errors, making its result subjective and invalid. The study of JC's genealogical tree on 6 generations, using longevity performance and TIAL (Total immediate ancestor longevity) indicators, shows how, in two centuries, her ancestors have been living 10% longer on average at each generation, increasingly overperforming their French 25-year-old contemporaries, from around 7% in the early 18th (...). Associations between Serum Levels of Cholesterol and Survival to Age 90 in Postmenopausal Women. Maihofer AX, Shadyab AH, Wild RA, LaCroix AZ. J Am Geriatr Soc. 2020 Jan 13. doi: 10.1111/jgs.16306. [Epub ahead of print] PMID: 31930739 Abstract OBJECTIVES: Although elevated lipid levels predict increased risk of coronary heart disease and death in middle-aged women and men, evidence is mixed if lipid levels measured in later life predict survival to very old ages. We examined lipid levels and survival to age 90 with or without intact mobility in a large cohort of older women. DESIGN: Prospective cohort. SETTING: Laboratory collection at a Women's Health Initiative (WHI) center and longitudinal follow-up via mail. PARTICIPANTS: Women aged 68 to 81 years at baseline. MEASUREMENTS: Serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were collected at baseline. Participant survival status and self-reported mobility was compared across lipid levels. RESULTS: HDL and LDL levels were not associated with survival to age 90 after adjustment for cardiovascular risk factors (HDL: quartile (Q) 2: odds ratio [OR] = 1.14 [95% confidence interval [CI] = .94-1.38]; Q3 OR = 1.08 [95% CI = .88-1.33]; Q4 OR = 1.09 [95% CI = .88-1.35]; LDL: Q2 OR = 1.07 [95% CI = .88-1.31]; Q3 OR = 1.27 [95% CI = 1.04-1.55]; Q4 OR = 1.07 [95% CI = .88-1.31]). Similarly, no associations were observed between HDL and LDL levels and survival to age 90 with mobility disability. High HDL was not associated with survival to age 90 with intact mobility after adjustment for other cardiovascular risk factors. Compared with the lowest LDL quartile, the three upper LDL quartiles were associated with greater odds of survival to age 90 with intact mobility (LDL: Q2 OR = 1.31 [95% CI = .99-1.74]; Q3 OR = 1.43 [95% CI = 1.07-1.92]; Q4 OR = 1.35 [95% CI = 1.01-1.80]; P = .05). CONCLUSION: Neither higher HDL nor lower LDL levels predicted survival to age 90, but higher LDL predicted healthy survival. These findings suggest the need for reevaluation of healthy LDL levels in older women. KEYWORDS: cholesterol; lipid; mobility; postmenopausal; quality of life High Dietary Intake of Vegetable or Polyunsaturated Fats is Associated With Reduced Risk of Hepatocellular Carcinoma. Yang W, Sui J, Ma Y, Simon TG, Petrick JL, Lai M, McGlynn KA, Campbell PT, Giovannucci EL, Chan AT, Zhang X. Clin Gastroenterol Hepatol. 2020 Jan 9. pii: S1542-3565(20)30035-5. doi: 10.1016/j.cgh.2020.01.003. [Epub ahead of print] PMID: 31927110 Abstract BACKGROUND & AIMS: We investigated associations of intake of total fats, specific dietary fats, and fats from different food sources with risk of hepatocellular carcinoma (HCC) using data from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). METHODS: We analyzed data from a total of 138,483 women and men who participated in the NHS or HPFS. A validated semi-quantitative food frequency questionnaire was sent to NHS participants in 1980, 1984, 1986, and every 4 years thereafter; dietary information was collected from participants in the HPFS in 1986 and every 4 years thereafter. Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression. RESULTS: After an average follow-up time of 26.6 years, 160 incident HCC cases were documented. Although there was a non-significant association between total fat intake and HCC, intake of vegetable fats reduced risk of HCC (HR for the highest vs lowest quartile, 0.61; 95% CI, 0.39-0.96; Ptrend=.02), but not animal or dairy fats. Replacing animal or dairy fats with an equivalent amount of vegetable fats was associated with a lower risk of HCC (HR per 1 standard deviation, 0.79; 95% CI, 0.65-0.97). Among fat subtypes, monounsaturated and polyunsaturated fatty acids, including n-3 (HR, 0.63; 95% CI, 0.41-0.96; Ptrend=.14) and n-6 polyunsaturated fatty acids (HR, 0.54; 95% CI, 0.34-0.86; Ptrend=.02), were inversely associated with risk of HCC. Higher ratios of monounsaturated or polyunsaturated fat to saturated fat were inversely associated with HCC risk (all Ptrend≤.02). In addition, when replacing saturated fats with monounsaturated or polyunsaturated fats, the HR per 1 standard deviation was 0.77 (95% CI, 0.64-0.92). CONCLUSIONS: In an analysis of data from 2 large cohort studies, we found higher intake of vegetable fats and polyunsaturated fats to be associated with lower risk of HCC. Replacing animal or dairy fats with vegetable fats, or replacing saturated fats with monounsaturated or polyunsaturated fats, was associated with reduced risk of HCC. KEYWORDS: PUFAs; dairy fat; liver cancer; primary prevention Effects of high-fiber diets enriched with carbohydrate, protein, or unsaturated fat on circulating short chain fatty acids: results from the OmniHeart randomized trial. Mueller NT, Zhang M, Juraschek SP, Miller ER, Appel LJ. Am J Clin Nutr. 2020 Jan 11. pii: nqz322. doi: 10.1093/ajcn/nqz322. [Epub ahead of print] PMID: 31927581 Abstract BACKGROUND: short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate) are produced by microbial fermentation of fiber in the colon. Evidence is lacking on how high-fiber diets that differ in macronutrient composition affect circulating SCFAs. OBJECTIVES: We aimed to compare the effects of 3 high-fiber isocaloric diets differing in %kcal of carbohydrate, protein, or unsaturated fat on circulating SCFAs. Based on previous literature, we hypothesized that serum acetate, the main SCFA in circulation, increases on all high-fiber diets, but differently by macronutrient composition of the diet. METHODS: OmniHeart is a randomized crossover trial of 164 men and women (≥30 y old); 163 participants with SCFA data were included in this analysis. We provided participants 3 isocaloric high-fiber (∼30 g/2100 kcal) diets, each for 6 wk, in random order: a carbohydrate-rich (Carb) diet, a protein-rich (Prot) diet (protein predominantly from plant sources), and an unsaturated fat-rich (Unsat) diet. We used LC-MS to quantify SCFA concentrations in fasting serum, collected at baseline and the end of each diet period. We fitted linear regression models with generalized estimating equations to examine change in ln-transformed SCFAs from baseline to the end of each diet; differences between diets; and associations of changes in SCFAs with cardiometabolic parameters. RESULTS: From baseline, serum acetate concentrations were increased by the Prot (β: 0.24; 95% CI: 0.12, 0.35), Unsat (β: 0.21; 95% CI: 0.10, 0.33), and Carb (β: 0.12; 95% CI: 0.01, 0.24) diets; between diets, only Prot compared with Carb was significant (P = 0.02). Propionate was decreased by the Carb (β: -0.10; 95% CI: -0.16, -0.03) and Unsat (β: -0.10; 95% CI: -0.16, -0.04) diets, not the Prot diet; between diet comparisons of Carb vs. Prot (P = 0.006) and Unsat vs. Prot (P = 0.002) were significant. The Prot diet increased butyrate (β: 0.05; 95% CI: 0.00, 0.09) compared with baseline, but not compared with the other diets. Increases in acetate were associated with decreases in insulin and glucose; increases in propionate with increases in leptin, LDL cholesterol, and blood pressure; and increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin (Ps < 0.05). CONCLUSIONS: Macronutrient composition of high-fiber diets affects circulating SCFAs, which are associated with measures of appetite and cardiometabolic health. KEYWORDS: acetate; butyrate; diet; fiber; macronutrient; microbiome; propionate; protein; short-chain fatty acids; unsaturated fat Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis. Alkhushaym N, Almutairi AR, Althagafi A, Fallatah SB, Oh M, Martin JR, Babiker HM, McBride A, Abraham I. Expert Opin Drug Saf. 2020 Jan 11. doi: 10.1080/14740338.2020.1715939. [Epub ahead of print] PMID: 31928106 Abstract Objectives: To estimate the pooled pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.Methods: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.Results: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. An overall association between PPI exposure and pancreatic cancer risk was observed (OR=1.75, 95%CI=1.12-2.72, I2=99%). This was confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose (DDD) of PPI exposure. In addition to the class effect for PPIs, rabeprazole had a singular significant association with pancreatic cancer (OR=5.40, 95%CI=1.98-14.703, I2=87.9%).Conclusion: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses, but was independent of duration, and Defined Daily Dose. KEYWORDS: meta-analysis; pancreatic cancer; proton pump inhibitors; risk The effects and associations of whole-apple intake on diverse cardiovascular risk factors. A narrative review. Sandoval-Ramírez BA, Catalán Ú, Calderón-Pérez L, Companys J, Pla-Pagà L, Ludwig IA, Romero MP, Solà R. Crit Rev Food Sci Nutr. 2020 Jan 13:1-14. doi: 10.1080/10408398.2019.1709801. [Epub ahead of print] PMID: 31928209 Abstract Apples are among the world's most consumed fruits. However, while the impact of whole-apple intake on cardiovascular disease (CVD) remains unknown. This narrative review summarizes a novel integrated view of whole-apple intake, CVD risk association (through observational studies; OSs), and the effects on CVD risk factors (randomized trials; RTs). In 8 OSs, whole-apple intake was associated with a reduced risk of CVD mortality, ischemic heart disease mortality, stroke mortality, all-cause mortality, and severe abdominal aortic calcification, as well as with lower C-reactive protein (CRP) concentrations. In 8 RTs, whole-apple consumption reduced total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and plasma inflammatory cytokines, and noticeably reduced CRP, whereas it increased high-density lipoprotein cholesterol (HDLc) and improved endothelial function. Thus, consuming between 100 and 150 g/day of whole apples is associated with a lower CVD risk and decreases in blood pressure, pulse pressure, total cholesterol, low-density lipoprotein cholesterol, and inflammation status as well as with increases in HDLc and endothelial function. These results, support the regular consumption of whole apples as an aid in the prevention of CVD. KEYWORDS: Apple; blood pressure; cardiovascular; cholesterol; health Modifiable risk factors for carotid atherosclerosis: a meta-analysis and systematic review. Ji X, Leng XY, Dong Y, Ma YH, Xu W, Cao XP, Hou XH, Dong Q, Tan L, Yu JT. Ann Transl Med. 2019 Nov;7(22):632. doi: 10.21037/atm.2019.10.115. PMID: 31930033 Abstract BACKGROUND: Carotid atherosclerosis is a major cause of stroke, but the conclusion about risk factors for carotid atherosclerosis is still controversial. The aim of our present meta-analysis and systematic review was to explore the modifiable risk factors for carotid atherosclerosis. METHODS: We searched PubMed from January 1962 to October 2018 to include longitudinal and cross-sectional studies. The results were pooled using random effects model. Heterogeneity was measured by I2 statistic and publication bias was assessed by funnel plots. RESULTS: A total of 14,700 articles were screened, of which 76 with 27 factors were eligible. Our meta-analysis of cross-sectional studies indicated nine factors (hyperlipidemia, hyperhomocysteinemia, hypertension, hyperuricemia, smoking, metabolic syndrome, hypertriglyceridemia, diabetes, and higher low density lipoprotein) were significantly associated with the presence of carotid plaque, among which four (hyperlipidemia, hyperhomocysteinemia, hypertension, and hyperuricemia) could elevate the risk of atherosclerosis by at least 50%; and one factor (hypertension) was associated with increased carotid intima-media thickness. In the systematic review, another five factors [negative emotion, socioeconomic strain, alcohol, air pollution, and obstructive sleep apnea syndrome (OSAS)] were also related to the presence of atherosclerosis. The cross-sectional associations with most of the above 14 factors were further confirmed by longitudinal studies. Among them, the managements of 4 factors (hypertension, hyperlipidemia, diabetes and OSAS) were indicated to prevent carotid atherosclerosis by cohort studies. CONCLUSIONS: Effective interventions targeting pre-existing disease, negative emotion, lifestyle and diet may reduce the risk of carotid atherosclerosis. Further good-quality prospective studies are needed to confirm these findings. KEYWORDS: Carotid atherosclerosis; carotid intima-media thickness; carotid plaque; meta-analysis; risk factors
  7. Bowel movement frequency and risks of major vascular and non-vascular diseases: a population-based cohort study among Chinese adults. Yang S, Yu C, Guo Y, Bian Z, Fan M, Yang L, Du H, Chen Y, Yan S, Zang Y, Chen J, Chen Z, Lv J, Li L; China Kadoorie Biobank Collaborative Group. BMJ Open. 2020 Jan 9;10(1):e031028. doi: 10.1136/bmjopen-2019-031028. PMID: 31924633 https://bmjopen.bmj.com/content/bmjopen/10/1/e031028.full.pdf Abstract OBJECTIVE: The application of bowel movement frequency (BMF) in primary care is limited by the lack of solid evidence about the associations of BMF with health outcomes apart from Parkinson's disease and colorectal cancer. We examined the prospective associations of BMF with major vascular and non-vascular diseases outside the digestive system. DESIGN: Population-based prospective cohort study. SETTING: The China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008. PARTICIPANTS: 487 198 participants aged 30 to 79 years without cancer, heart disease or stroke at baseline were included and followed up for a median of 10 years. The usual BMF was self-reported once at baseline. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident events of predefined major vascular and non-vascular diseases. RESULTS: In multivariable-adjusted analyses, participants having bowel movements 'more than once a day' had higher risks of ischaemic heart disease (IHD), heart failure, chronic obstructive pulmonary disease, type 2 diabetes mellitus and chronic kidney disease (CKD) when compared with the reference group ('once a day'). The respective HRs (95% CIs) were 1.12 (1.09 to 1.16), 1.33 (1.22 to 1.46), 1.28 (1.22 to 1.36), 1.20 (1.15 to 1.26) and 1.15 (1.07 to 1.24). The lowest BMF ('less than three times a week') was also associated with higher risks of IHD, major coronary events, ischaemic stroke and CKD. The respective HRs were 1.07 (1.02 to 1.12), 1.22 (1.10 to 1.36), 1.11 (1.05 to 1.16) and 1.20 (1.07 to 1.35). CONCLUSION: BMF was associated with future risks of multiple vascular and non-vascular diseases. The integration of BMF assessment and health counselling into primary care should be considered. KEYWORDS: chronic diseases; cohort study; epidemiology; public health Severe food restriction activates the central renin angiotensin system. De Souza AMA, Linares A, Speth RC, Campos GV, Ji H, Chianca D Jr, Sandberg K, De Menezes RCA. Physiol Rep. 2020 Jan;8(1):e14338. doi: 10.14814/phy2.14338. PMID: 31925945 https://physoc.onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.14338 Abstract We previously showed that 2 weeks of a severe food restricted (sFR) diet (40% of the caloric intake of the control (CT) diet) up-regulated the circulating renin angiotensin (Ang) system (RAS) in female Fischer rats, most likely as a result of the fall in plasma volume. In this study, we investigated the role of the central RAS in the mean arterial pressure (MAP) and heart rate (HR) dysregulation associated with sFR. Although sFR reduced basal mean MAP and HR, the magnitude of the pressor response to intracerebroventricular (icv) microinjection of Ang-[1-8] was not affected; however, HR was 57 ± 13 bpm lower 26 min after Ang-[1-8] microinjection in the sFR rats and a similar response was observed after losartan was microinjected. The major catabolic pathway of Ang-[1-8] in the hypothalamus was via Ang-[1-7]; however, no differences were detected in the rate of Ang-[1-8] synthesis or degradation between CT and sFR animals. While sFR had no effect on the AT1 R binding in the subfornical organ (SFO), the organum vasculosum laminae terminalis (OVLT) and median preoptic nucleus (MnPO) of the paraventricular anteroventral third ventricle, ligand binding increased 1.4-fold in the paraventricular nucleus (PVN) of the hypothalamus. These findings suggest that sFR stimulates the central RAS by increasing AT1 R expression in the PVN as a compensatory response to the reduction in basal MAP and HR. These findings have implications for people experiencing a period of sFR since an activated central RAS could increase their risk of disorders involving over activation of the RAS including renal and cardiovascular diseases. KEYWORDS: RAS-Fingerprint®; angiotensin converting enzyme (ACE); angiotensin converting enzyme 2 (ACE2); caloric reduction; inadequate food intake Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma. Mukherjee P, Augur ZM, Li M, Hill C, Greenwood B, Domin MA, Kondakci G, Narain NR, Kiebish MA, Bronson RT, Arismendi-Morillo G, Chinopoulos C, Seyfried TN. Commun Biol. 2019 May 29;2(1):200. doi: 10.1038/s42003-019-0455-x. PMID: 31925059 Abstract Glioblastoma (GBM) is an aggressive primary human brain tumour that has resisted effective therapy for decades. Although glucose and glutamine are the major fuels that drive GBM growth and invasion, few studies have targeted these fuels for therapeutic management. The glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), was administered together with a calorically restricted ketogenic diet (KD-R) to treat late-stage orthotopic growth in two syngeneic GBM mouse models: VM-M3 and CT-2A. DON targets glutaminolysis, while the KD-R reduces glucose and, simultaneously, elevates neuroprotective and non-fermentable ketone bodies. The diet/drug therapeutic strategy killed tumour cells while reversing disease symptoms, and improving overall mouse survival. The therapeutic strategy also reduces edema, hemorrhage, and inflammation. Moreover, the KD-R diet facilitated DON delivery to the brain and allowed a lower dosage to achieve therapeutic effect. The findings support the importance of glucose and glutamine in driving GBM growth and provide a therapeutic strategy for non-toxic metabolic management.
  8. AlPater

    Al's CR updates

    Promoting healthspan and lifespan with caloric restriction in primates. Pifferi F, Terrien J, Perret M, Epelbaum J, Blanc S, Picq JL, Dhenain M, Aujard F. Commun Biol. 2019 Mar 15;2(1):107. doi: 10.1038/s42003-019-0348-z. No abstract available. PMID: 31924947 https://www.nature.com/articles/s42003-019-0348-z.pdf
  9. Tea consumption and risk of stroke in Chinese adults: a prospective cohort study of 0.5 million men and women. Tian T, Lv J, Jin G, Yu C, Guo Y, Bian Z, Yang L, Chen Y, Shen H, Chen Z, Hu Z, Li L; China Kadoorie Biobank Collaborative Group. Am J Clin Nutr. 2020 Jan 1;111(1):197-206. doi: 10.1093/ajcn/nqz274. PMID: 31711152 Abstract BACKGROUND: Many cohort studies have explored the relation between tea consumption and stroke risk; however, the conclusions have been inconsistent. In addition, evidence is lacking in China, where the patterns of tea consumption and main types of tea consumed differ substantially from those in high-income countries. OBJECTIVE: We aimed to systematically assess the association of tea consumption with the risk of stroke based on a Chinese large-scale cohort study. METHODS: A total of 487,377 participants from the China Kadoorie Biobank were included in the present study. Detailed information about tea consumption (including frequency, duration, amount, and tea type) was self-reported at baseline. After ∼4.3 million person-years of follow-up, 38,727 incident cases of stroke were recorded, mainly through linkage with mortality and morbidity registries and based on the national health insurance system. RESULTS: Overall, 128,280 adults (26.3%) reported drinking tea almost daily (41.4% men, 15.9% women), predominantly green tea (86.7%). Tea consumption had an inverse and dose-response relation with the risk of stroke (Ptrend < 0.001). Compared with nonconsumers, those who consumed tea occasionally, weekly, and daily had adjusted HRs and 95% CIs of 0.96 (0.94, 0.99), 0.94 (0.90, 0.98), and 0.92 (0.89, 0.95) respectively, with little difference by stroke type. Among those who consumed tea daily, the HRs for stroke decreased with the increasing duration and amount of tea consumed (all P < 0.001). These inverse associations were significant for green tea but not for other types of tea. Among men, but not women, the inverse relations could be detected, and similar inverse associations could be found for male noncurrent alcohol-consumers and noncurrent smokers as well. CONCLUSIONS: Among Chinese adults, higher consumption of tea, especially green tea, was associated with a lower risk of ischemic and hemorrhagic stroke. Serum magnesium and risk of coronary artery disease: are there implications for dietary interventions? van Dam RM. Am J Clin Nutr. 2020 Jan 1;111(1):6-7. doi: 10.1093/ajcn/nqz289. No abstract available. PMID: 31732727 https://sci-hub.tw/10.1093/ajcn/nqz289 >>>>>>>>>>>>>>>>>>> Serum magnesium and the incidence of coronary artery disease over a median 27 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study and a meta-analysis. Rooney MR, Alonso A, Folsom AR, Michos ED, Rebholz CM, Misialek JR, Chen LY, Dudley S, Lutsey PL. Am J Clin Nutr. 2020 Jan 1;111(1):52-60. doi: 10.1093/ajcn/nqz256. PMID: 31622458 Abstract BACKGROUND: Low serum magnesium (Mg) concentrations have been associated with higher coronary artery disease (CAD) risk. A previous Atherosclerosis Risk in Communities (ARIC) Study article that evaluated the Mg-CAD association, based on 319 events occurring over 4-7 y, identified a sex-interaction whereby the inverse Mg-CAD association was much stronger among women than men. More than 1700 additional ARIC CAD events have since accrued. OBJECTIVE: We aimed to test our hypothesis that serum Mg is inversely and independently associated with long-term CAD risk in ARIC and in a meta-analysis with other prospective studies. METHODS: A total of 14,446 ARIC study participants (baseline mean ± SD age: 54 ± 6 y, 57% women, 27% African American) were followed for incident CAD through 2017. CAD events were defined by myocardial infarction or CAD mortality. Serum Mg was modeled as quintiles based on mean visit 1 (1987-1989) and visit 2 (1990-1992) concentrations. Cox regression models were used. We also conducted a random-effects meta-analysis incorporating these contemporary ARIC findings. RESULTS: Over a median follow-up of 27 y, 2131 incident CAD cases accrued. Overall, low serum Mg was associated with higher CAD risk after adjustment for demographics, lifestyle factors, and other CAD risk factors than was higher serum Mg (HR Q1 compared with Q5: 1.28; 95% CI: 1.11, 1.47; P-linear trend <0.001). The association was stronger among women (HR Q1 compared with Q5: 1.53; 95% CI: 1.22, 1.92) than men (HR: 1.11; 95% CI: 0.92, 1.34) (P-interaction = 0.05). In the meta-analysis including 5 studies, the pooled RR (95% CI) for CAD in the lowest compared with the highest circulating Mg category was 1.18 (1.06, 1.31) (I2 = 22%, P-heterogeneity = 0.27). CONCLUSIONS: In this large community-based cohort and updated meta-analysis, low circulating Mg was associated with higher CAD risk than was higher Mg. Whether increasing Mg concentrations within healthy limits is a useful strategy for CAD prevention remains to be seen. KEYWORDS: circulating magnesium; cohort study; coronary artery disease; meta-analysis; observational prospective studies FGF21, not GCN2, influences bone morphology due to dietary protein restrictions. McNulty MA, Goupil BA, Albarado DC, Castaño-Martinez T, Ambrosi TH, Puh S, Schulz TJ, Schürmann A, Morrison CD, Laeger T. Bone Rep. 2019 Dec 31;12:100241. doi: 10.1016/j.bonr.2019.100241. eCollection 2020 Jun. PMID: 31921941 https://www.sciencedirect.com/science/article/pii/S2352187219300476?via%3Dihub Abstract BACKGROUND: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone. METHODS: Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (μCT) for changes in trabecular and cortical architecture and mass. RESULTS: In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture. CONCLUSIONS: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21. KEYWORDS: Dietary restriction; FGF21; GCN2; Microcomputed tomography; Protein restriction Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial. Oikawa SY, Kamal MJ, Webb EK, McGlory C, Baker SK, Phillips SM. Am J Clin Nutr. 2020 Jan 9. pii: nqz332. doi: 10.1093/ajcn/nqz332. [Epub ahead of print] PMID: 31919527 Abstract BACKGROUND: Aging appears to attenuate the response of skeletal muscle protein synthesis (MPS) to anabolic stimuli such as protein ingestion (and the ensuing hyperaminoacidemia) and resistance exercise (RE). OBJECTIVES: The purpose of this study was to determine the effects of protein quality on feeding- and feeding plus RE-induced increases of acute and longer-term MPS after ingestion of whey protein (WP) and collagen protein (CP). METHODS: In a double-blind parallel-group design, 22 healthy older women (mean ± SD age: 69 ± 3 y, n = 11/group) were randomly assigned to consume a 30-g supplement of either WP or CP twice daily for 6 d. Participants performed unilateral RE twice during the 6-d period to determine the acute (via [13C6]-phenylalanine infusion) and longer-term (ingestion of deuterated water) MPS responses, the primary outcome measures. RESULTS: Acutely, WP increased MPS by a mean ± SD 0.017 ± 0.008%/h in the feeding-only leg (Rest) and 0.032 ± 0.012%/h in the feeding plus exercise leg (Exercise) (both P < 0.01), whereas CP increased MPS only in Exercise (0.012 ± 0.013%/h) (P < 0.01) and MPS was greater in WP than CP in both the Rest and Exercise legs (P = 0.02). Longer-term MPS increased by 0.063 ± 0.059%/d in Rest and 0.173 ± 0.104%/d in Exercise (P < 0.0001) with WP; however, MPS was not significantly elevated above baseline in Rest (0.011 ± 0.042%/d) or Exercise (0.020 ± 0.034%/d) with CP. Longer-term MPS was greater in WP than in CP in both Rest and Exercise (P < 0.001). CONCLUSIONS: Supplementation with WP elicited greater increases in both acute and longer-term MPS than CP supplementation, which is suggestive that WP is a more effective supplement to support skeletal muscle retention in older women than CP. KEYWORDS: collagen peptides; muscle protein synthesis; older women; protein quality; resistance exercise; whey protein Modest improvement in CVD risk markers in older adults following quinoa (Chenopodium quinoa Willd.) consumption: a randomized-controlled crossover study with a novel food product. Pourshahidi LK, Caballero E, Osses A, Hyland BW, Ternan NG, Gill CIR. Eur J Nutr. 2020 Jan 9. doi: 10.1007/s00394-019-02169-0. [Epub ahead of print] PMID: 31919583 Abstract PURPOSE: To investigate the effect of consuming quinoa biscuits on markers of CVD risk over 4 weeks in free-living older adults. METHODS: A randomized-controlled, double-blind crossover trial was conducted in which consenting healthy adults aged 50-75 years (n = 40) consumed 15 g quinoa biscuits (60 g quinoa flour/100 g) or control iso-energetic biscuits (made using wheat flour) daily for 28 consecutive days (4 weeks), in addition to their normal diet. Following a 6-week washout, participants consumed the alternate biscuit for a final 4 weeks. Anthropometry and fasted blood samples were obtained before and after each intervention period. RESULTS: At the beginning of the trial, mean ± SD total cholesterol concentrations were 6.02 ± 1.22 mmol/L (3.7-9.2 mmol/L); 33 participants (82.5%) had high cholesterol (> 5 mmol/L). No participants were lost to follow-up and there were no changes in habitual dietary intakes or levels of physical activity between each 4-week intervention period. Significantly greater decreases in total and LDL cholesterol concentrations (- 0.30 ± 0.58 and - 0.25 ± 0.38 mmol/L, respectively), TC: HDL ratio (- 0.11 ± 0.30), weight (- 0.61 ± 0.89 kg) and BMI (- 0.22 ± 0.34 kg/m2) were apparent following consumption of the quinoa versus control biscuits (all P < 0.05). Changes in triglycerides, HDL cholesterol, or PUFA or CRP concentrations were not significant between treatment groups. CONCLUSION: Consumption of novel quinoa biscuits produced small, but favorable changes in body weight, BMI, and circulating cholesterol concentrations, all of which may contribute to lowered CVD risk in older adults. KEYWORDS: Cardiovascular disease; Cholesterol; Fatty acids; PUFA; Quinoa; Randomized controlled trial
  10. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Braidy N, Liu Y. Exp Gerontol. 2020 Jan 6:110831. doi: 10.1016/j.exger.2020.110831. [Epub ahead of print] Review. PMID: 31917996 Abstract Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials. KEYWORDS: Ageing; Cellular energetics; NAD+; Nicotinamide; Oxidative stress Tea consumption and the risk of atherosclerotic cardiovascular disease and all-cause mortality: The China-PAR project. Wang X, Liu F, Li J, Yang X, Chen J, Cao J, Wu X, Lu X, Huang J, Li Y, Zhao L, Shen C, Hu D, Yu L, Liu X, Wu X, Wu S, Gu D. Eur J Prev Cardiol. 2020 Jan 8:2047487319894685. doi: 10.1177/2047487319894685. [Epub ahead of print] PMID: 31914807 Abstract AIMS: The role of tea consumption in the primary prevention of atherosclerotic cardiovascular disease remains unclear in cohort studies. This prospective cohort study aimed to investigate the associations of tea consumption with the risk of atherosclerotic cardiovascular disease and all-cause mortality. METHODS: We included 100,902 general Chinese adults from the project of Prediction for ASCVD Risk in China (China-PAR) in 15 provinces across China since 1998. Information on tea consumption was collected through standardized questionnaires. Outcomes were identified by interviewing study participants or their proxies, and checking hospital records and/or death certificates. Cox proportional hazard regression models were used to calculate hazard ratios and their corresponding 95% confidence intervals related to tea consumption. RESULTS: During a median follow-up of 7.3 years, 3683 atherosclerotic cardiovascular disease events, 1477 atherosclerotic cardiovascular disease deaths, and 5479 all-cause deaths were recorded. Compared with never or non-habitual tea drinkers, the hazard ratio and 95% confidence interval among habitual tea drinkers was 0.80 (0.75-0.87), 0.78 (0.69-0.88), and 0.85 (0.79-0.90) for atherosclerotic cardiovascular disease incidence, atherosclerotic cardiovascular disease mortality, and all-cause mortality, respectively. Habitual tea drinkers had 1.41 years longer of atherosclerotic cardiovascular disease-free years and 1.26 years longer of life expectancy at the index age of 50 years. The observed inverse associations were strengthened among participants who kept the habit during the follow-up period. CONCLUSION: Tea consumption was associated with reduced risks of atherosclerotic cardiovascular disease and all-cause mortality, especially among those consistent habitual tea drinkers. KEYWORDS: Chinese population; Tea consumption; all-cause mortality; atherosclerotic cardiovascular disease; prospective cohort study Associations of choline-related nutrients with cardiometabolic and all-cause mortality: results from 3 prospective cohort studies of blacks, whites, and Chinese. Yang JJ, Lipworth LP, Shu XO, Blot WJ, Xiang YB, Steinwandel MD, Li H, Gao YT, Zheng W, Yu D. Am J Clin Nutr. 2020 Jan 8. pii: nqz318. doi: 10.1093/ajcn/nqz318. [Epub ahead of print] PMID: 31915809 Abstract BACKGROUND: Choline-related nutrients are dietary precursors of a gut microbial metabolite, trimethylamine-N-oxide, which has been linked to cardiometabolic diseases and related death. However, epidemiologic evidence on dietary choline and mortality remains limited, particularly among nonwhite populations. OBJECTIVES: This study aimed to investigate the associations of choline-related nutrients with cardiometabolic and all-cause mortality among black and white Americans and Chinese adults. METHODS: Included were 49,858 blacks, 23,766 whites, and 134,001 Chinese, aged 40-79 y, who participated in 3 prospective cohorts and lived ≥1 y after enrollment. Cox regression models were used to estimate HRs and 95% CIs for cardiometabolic [e.g., ischemic heart disease (IHD), stroke, and diabetes] and all-cause deaths. To account for multiple testing, P values < 0.003 were considered significant. RESULTS: Mean choline intake among blacks, whites, and Chinese was 404.1 mg/d, 362.0 mg/d, and 296.8 mg/d, respectively. During a median follow-up of 11.7 y, 28,673 deaths were identified, including 11,141 cardiometabolic deaths. After comprehensive adjustments, including for overall diet quality and disease history, total choline intake was associated with increased cardiometabolic mortality among blacks and Chinese (HR for highest compared with lowest quintile: 1.26; 95% CI: 1.13, 1.40 and HR: 1.23; 95% CI: 1.11, 1.38, respectively; both P-trend < 0.001); among whites, the association was weaker (HR: 1.12; 95% CI: 0.95, 1.33; P-trend = 0.02). Total choline intake was also associated with diabetes and all-cause mortality in blacks (HR: 1.66; 95% CI: 1.26, 2.19 and HR: 1.20; 95% CI: 1.12, 1.29, respectively), with diabetes mortality in Chinese (HR: 2.24; 95% CI: 1.68, 2.97), and with IHD mortality in whites (HR: 1.31; 95% CI: 1.02, 1.69) (all P-trend < 0.001). The choline-mortality association was modified by alcohol consumption and appeared stronger among individuals with existing cardiometabolic disease. Betaine intake was associated with increased cardiometabolic mortality in Chinese only (HR: 1.16; 95% CI: 1.08, 1.25; P-trend < 0.001). CONCLUSIONS: High choline intake was associated with increased cardiometabolic mortality in racially diverse populations. Legume and soy intake and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies. Tang J, Wan Y, Zhao M, Zhong H, Zheng JS, Feng F. Am J Clin Nutr. 2020 Jan 8. pii: nqz338. doi: 10.1093/ajcn/nqz338. [Epub ahead of print] PMID: 31915830 Abstract BACKGROUND: Previous findings on the associations of legume and soy intake with the risk of type 2 diabetes are conflicting. OBJECTIVE: We aimed to summarize the longitudinal associations between legume and soy intake and risk of type 2 diabetes. METHODS: We searched for relevant prospective cohort studies in PubMed, EMBASE, and Ovid up to August 2019. Study-specific, multivariable-adjusted RRs and 95% CIs were pooled by random-effects models. RESULTS: We identified 15 unique cohorts including 565,810 individuals and 32,093 incident cases. The summary RRs (95% CIs) of incident type 2 diabetes were 0.95 (0.79, 1.14; NS) for total legumes, 0.83 (0.68, 1.01; NS) for total soy, 0.89 (0.71, 1.11; NS) for soy milk, 0.92 (0.84, 0.99) for tofu, 0.84 (0.75, 0.95) for soy protein, and 0.88 (0.81, 0.96) for soy isoflavones, respectively. High heterogeneity was found for total legumes (I2 = 84.8%), total soy (I2 = 90.8%), and soy milk (I2 = 91.7%). Potential sources of heterogeneity were not evident for total legumes or soy milk, whereas for total soy, geographic location (Asia, United States; P = 0.04) and study quality (high, moderate, or low; P = 0.02) significantly predicted heterogeneity. In dose-response analysis, significant linear inverse associations were observed for tofu, soy protein, and soy isoflavones (all P < 0.05). Overall quality of evidence was rated as moderate for total legumes and low for total soy and soy subtypes. CONCLUSIONS: Dietary intakes of tofu, soy protein, and soy isoflavones, but not total legumes or total soy, are inversely associated with incident type 2 diabetes. Our findings support recommendations to increase intakes of certain soy products for the prevention of type 2 diabetes. However, the overall quality of evidence was low and more high-quality evidence from prospective studies is needed. This trial was registered as PROSPERO CRD42019126403 (https://www.crd.york.ac.uk/PROSPERO). KEYWORDS: cohort; legume; meta-analysis; soy; type 2 diabetes Food Products That May Cause an Increase in Blood Pressure. Adamczak M, Wiecek A. Curr Hypertens Rep. 2020 Jan 8;22(1):2. doi: 10.1007/s11906-019-1007-y. Review. PMID: 31915940 Abstract PURPOSE OF REVIEW: To review latest reports of the food products which might increase blood pressure and therefore might participate in the pathogenesis of hypertension. RECENT FINDINGS: Results of clinical study suggest that consumption of high-sodium food leads to transient increase in plasma sodium concentration. This is accompanied by blood pressure increase. Results of both clinical and experimental studies suggest direct vasculotoxic effects of sodium. Increased plasma sodium concentration could mediate its effects on blood pressure by changes in endothelial cell stiffness and glycocalyx integrity. Energy drinks are non-alcoholic beverages with increasing popularity. Clinical, interventional, randomized, placebo controlled, and cross-sectional studies showed that energy drinks may increase arterial blood pressure. Blood pressure increase after exposure for the energy drinks is mainly related to the caffeine content in these drinks. Many case reports were published concerning the clinically significant increase in blood pressure caused by the consumption of liquorice root or food products containing liquorice, such as candies, tea, Pontefract cookies, and chewing gum. Liquorice contains a precursor of glycyrrhetic acid. Glycyrrhetic acid reduces the activity of the 11β-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) isoenzyme, which leads to activation of the mineralocorticoid receptor by cortisol in the distal convoluted tubule resulting in hypertension, hypokalemia, and metabolic alkalosis. The relationship between chronic alcohol intake and blood pressure is well established on the basis of a diverse body of evidence including animal experiments, epidemiological studies, mendelian randomization studies, and interventional studies. Results of recent studies suggested that binge drinking (i.e., episodic consumption of a very high amount of alcohol beverages) has pronounced hypertensinogenic effects. Recently, it was documented that also low doses of alcohol may increase the risk of cardiovascular complications. Therefore, the amount of alcohol consumption that is safe is zero. High-salt food products, energy drinks, food products containing liquorice, and alcoholic beverages have hypertensinogenic properties. Patients with hypertension and other cardiovascular diseases should avoid even accidental consumption of these food products. KEYWORDS: Alcohol and hypertension; Blood pressure; Cardiovascular disease; Diet and hypertension; Salt and hypertension; Salt intake
  11. Midlife socioeconomic position and old-age dementia mortality: a large prospective register-based study from Finland. Korhonen K, Einiö E, Leinonen T, Tarkiainen L, Martikainen P. BMJ Open. 2020 Jan 6;10(1):e033234. doi: 10.1136/bmjopen-2019-033234. PMID: 31911519 Abstract OBJECTIVES: To assess the association between multiple indicators of socioeconomic position and dementia-related death, and to estimate the contribution of dementia to socioeconomic differences in overall mortality at older ages. DESIGN: Prospective population-based register study. SETTING: Finland. PARTICIPANTS: 11% random sample of the population aged 70-87 years resident in Finland at the end of year 2000 (n=54 964). MAIN OUTCOME MEASURE: Incidence rates, Kaplan-Meier survival probabilities and Cox regression HRs of dementia mortality in 2001-2016 by midlife education, occupational social class and household income measured at ages 53-57 years. RESULTS: During the 528 387 person-years at risk, 11 395 individuals died from dementia (215.7 per 10 000 person-years). Lower midlife education, occupational social class and household income were associated with higher dementia mortality, and the differences persisted to the oldest old ages. Compared with mortality from all other causes, however, the socioeconomic differences emerged later. Dementia accounted for 28% of the difference between low and high education groups in overall mortality at age 70+ years, and for 21% of the difference between lowest and highest household income quintiles. All indicators of socioeconomic position were independently associated with dementia mortality, low household income being the strongest independent predictor (HR=1.24, 95% CI 1.16 to 1.32), followed by basic education (HR=1.14, 1.06 to 1.23). Manual occupational social class was related to a 6% higher hazard (HR=1.06, 1.01 to 1.11) compared with non-manual social class. Adjustment for midlife economic activity, baseline marital status and chronic health conditions attenuated the excess hazard of low midlife household income, although significant effects remained. CONCLUSION: Several indicators of socioeconomic position predict dementia mortality independently and socioeconomic inequalities persist into the oldest old ages. The results demonstrate that dementia is among the most important contributors to socioeconomic inequalities in overall mortality at older ages. KEYWORDS: Alzheimer's disease; dementia; register study; socioeconomic factors Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer. Genkinger JM, Wu K, Wang M, Albanes D, Black A, van den Brandt PA, Burke KA, Cook MB, Gapstur SM, Giles GG, Giovannucci E, Goodman GG, Goodman PJ, Håkansson N, Key TJ, Männistö S, Le Marchand L, Liao LM, MacInnis RJ, Neuhouser ML, Platz EA, Sawada N, Schenk JM, Stevens VL, Travis RC, Tsugane S, Visvanathan K, Wilkens LR, Wolk A, Smith-Warner SA. Ann Oncol. 2020 Jan;31(1):103-114. doi: 10.1016/j.annonc.2019.09.007. PMID: 31912782 Abstract BACKGROUND: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk. PATIENTS AND METHODS: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models. RESULTS: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m2 with 21-22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m. CONCLUSION: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer. KEYWORDS: BMI; body fatness; height; pooled analysis; prostate cancer; waist Cancer death rate in U.S. shows large one-year drop Report 'shows a continued striking decline in overall cancer mortality in the United States' Thomson Reuters · Posted: Jan 08, 2020 https://www.cbc.ca/news/health/cancer-death-rate-acs-1.5419255 'excess body weight currently accounts for about seven per cent of cancers. "I'm sure that proportion will continue to increase because it takes a decade or two before you see the influence on exposure reflected in cancer rates."' Risk Factors For Hyperuricemia In Chinese Centenarians And Near-Centenarians. Han QX, Zhang D, Zhao YL, Liu L, Li J, Zhang F, Luan FX, Liu DW, Liu ZS, Cai GY, Chen XM, Zhu HY. Clin Interv Aging. 2019 Dec 19;14:2239-2247. doi: 10.2147/CIA.S223048. eCollection 2019. PMID: 31908434 Abstract PURPOSE: Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians. PATIENTS AND METHODS: In total, 966 centenarians and 788 near-centenarians were included. Community-based surveys were conducted to collect information about lifestyle. Blood examinations were performed using enzymatic assays. T-tests and χ2 tests were used to investigate significant indicators of hyperuricemia, and multivariate logistic regression was used to analyze the related risk factors. A comprehensive analysis of nineteen modifiable factors, including lifestyle characteristics, dietary habits, general characteristics and blood test indexes, was conducted. RESULTS: The prevalence of hyperuricemia was 29.02%. The percentage of men, waist circumference (WC), waist-hip ratio, estimated glomerular filtration rate (eGFR), levels of total protein (TP), alanine aminotransferase, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, serum homocysteine, serum uric acid, serum urea and serum creatinine, passive smoking, alcohol consumption, snoring, preference for fried flavors, and meat, seafood and vegetable consumption were significantly different between the hyperuricemia group and the normouricemia group (p<0.05). Multivariate logistic regression analysis showed that WC (OR=1.020), eGFR (OR=0.960), TP level (OR=1.038), serum urea level (OR=1.154), passive smoking (OR=2.589), snoring (OR=2.003), meat consumption (OR=2.506), seafood consumption (OR=1.422) and vegetable consumption (OR=0.521) were significantly associated with the risk of hyperuricemia (p<0.05). CONCLUSION: Low eGFR and vegetable consumption, high WC, TP, and serum urea levels, passive smoking, snoring, and high meat and seafood consumption were independent risk factors for hyperuricemia. It is recommended that people at high risk for hyperuricemia should actively limit their intake of fried food, alcohol and purine-rich food, increase their intake of fresh vegetables, actively treat sleep apnea syndrome, avoid passive smoking, maintain a healthy WC and seek to improve their kidney and liver function. KEYWORDS: centenarians; dietary; hyperuricemia; lifestyle; risk factors Physical activity, sedentary leisure-time and risk of incident type 2 diabetes: a prospective study of 512 000 Chinese adults. Bennett DA, Du H, Bragg F, Guo Y, Wright N, Yang L, Bian Z, Chen Y, Yu C, Wang S, Meng F, Lv J, Chen J, Li L, Clarke R, Chen Z; China Kadoorie Biobank Study Collaborative Group . BMJ Open Diabetes Res Care. 2019 Dec 18;7(1):e000835. doi: 10.1136/bmjdrc-2019-000835. eCollection 2019. PMID: 31908799 Abstract OBJECTIVE: Aim to examine the independent and joint associations of physical activity (PA) and sedentary leisure-time (SLT) with risk of diabetes and assess the extent to which these associations were mediated by adiposity. RESEARCH DESIGN AND METHODS: The prospective China Kadoorie Biobank recruited ~512 000 adults from 10 diverse areas across China. Self-reported PA was estimated based on type, frequency and duration of specific types of PA, covering four domains (occupation, leisure, household and commuting). SLT was defined as hours per day spent watching television, reading or playing card games. Stratified Cox proportional hazards models were used to estimate adjusted HRs (aHRs) for PA and SLT associated with incident diabetes. Analyses were stratified by age-at-risk (5-year intervals), sex and region and adjusted for household income, education, alcohol consumption, smoking, fresh fruit intake, self-reported general health status, family history of diabetes and body mass index (BMI) status. Analyses of total PA, occupational and non-occupational PA and SLT were mutually adjusted for each other, as appropriate. RESULTS: After ~9 years of follow-up, there were 14 940 incident diabetes cases among 460 736 participants without prior diabetes or cardiovascular diseases at baseline. The mean (SD) age at baseline was 51 (10.6) years, 59% were women and 43% resided in urban areas. Overall, the mean BMI was 23.5 (3.3) kg/m2, which differed by ~0.5 kg/m2 among individuals in the highest compared with the lowest PA and SLT groups. PA was inversely associated the risk of diabetes 16% (aHR: 0.84, 95% CI 0.81 to 0.88) lower in top than bottom fifth. After further adjustment for BMI this was attenuated to 0.99 (95% CI 0.98 to 1.00). SLT was positively associated with diabetes and each 1 hour per day higher usual level was associated with aHR of 1.13 (95% CI 1.09 to 1.17) for diabetes, attenuated to 1.05 (95% CI 1.01 to 1.09) after further adjustment for BMI. CONCLUSIONS: Among Chinese adults, higher levels of PA and lower levels of SLT were associated with lower risks of diabetes with no evidence of effect modification by each other. These associations appeared to arise mainly through adiposity. KEYWORDS: adiposity; physical activity; sedentary leisure-time; type 2 diabetes Replacing Saturated Fats with Unsaturated Fats from Walnuts or Vegetable Oils Lowers Atherogenic Lipoprotein Classes Without Increasing Lipoprotein(a). Tindall AM, Kris-Etherton PM, Petersen KS. J Nutr. 2020 Jan 7. pii: nxz313. doi: 10.1093/jn/nxz313. [Epub ahead of print] PMID: 31909809 Abstract BACKGROUND: Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood. OBJECTIVES: We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS: A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis. RESULTS: Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets. CONCLUSIONS: In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9. KEYWORDS: PCSK9; cholesterol efflux; lipids; lipoproteins; walnut
  12. AlPater

    Al's CR updates

    Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction. Jiang Y, Yan F, Feng Z, Lazarovici P, Zheng W. Cells. 2019 Dec 31;9(1). pii: E100. doi: 10.3390/cells9010100. Review. PMID: 31906091 Abstract Dietary restriction (DR), which is defined as a reduction of particular or total nutrient intake without causing malnutrition, has been proved to be a robust way to extend both lifespan and health-span in various species from yeast to mammal. However, the molecular mechanisms by which DR confers benefits on longevity were not yet fully elucidated. The forkhead box O transcription factors (FOXOs), identified as downstream regulators of the insulin/IGF-1 signaling pathway, control the expression of many genes regulating crucial biological processes such as metabolic homeostasis, redox balance, stress response and cell viability and proliferation. The activity of FOXOs is also mediated by AMP-activated protein kinase (AMPK), sirtuins and the mammalian target of rapamycin (mTOR). Therefore, the FOXO-related pathways form a complex network critical for coordinating a response to environmental fluctuations in order to maintain cellular homeostasis and to support physiological aging. In this review, we will focus on the role of FOXOs in different DR interventions. As different DR regimens or calorie (energy) restriction mimetics (CRMs) can elicit both distinct and overlapped DR-related signaling pathways, the benefits of DR may be maximized by combining diverse forms of interventions. In addition, a better understanding of the precise role of FOXOs in different mechanistic aspects of DR response would provide clear cellular and molecular insights on DR-induced increase of lifespan and health-span. KEYWORDS: AMPK; FOXO; calorie restriction mimetics; dietary restriction; insulin/IGF-1 signaling pathway; longevity; mTOR; sirtuins Energy Restriction and Colorectal Cancer: A Call for Additional Research. Castejón M, Plaza A, Martinez-Romero J, Fernandez-Marcos PJ, Cabo R, Diaz-Ruiz A. Nutrients. 2020 Jan 1;12(1). pii: E114. doi: 10.3390/nu12010114. Review. PMID: 31906264 Abstract : Colorectal cancer has the second highest cancer-related mortality rate, with an estimated 881,000 deaths worldwide in 2018. The urgent need to reduce the incidence and mortality rate requires innovative strategies to improve prevention, early diagnosis, prognostic biomarkers, and treatment effectiveness. Caloric restriction (CR) is known as the most robust nutritional intervention that extends lifespan and delays the progression of age-related diseases, with remarkable results for cancer protection. Other forms of energy restriction, such as periodic fasting, intermittent fasting, or fasting-mimicking diets, with or without reduction of total calorie intake, recapitulate the effects of chronic CR and confer a wide range of beneficial effects towards health and survival, including anti-cancer properties. In this review, the known molecular, cellular, and organismal effects of energy restriction in oncology will be discussed. Energy-restriction-based strategies implemented in colorectal models and clinical trials will be also revised. While energy restriction constitutes a promising intervention for the prevention and treatment of several malignant neoplasms, further investigations are essential to dissect the interplay between fundamental aspects of energy intake, such as feeding patterns, fasting length, or diet composition, with all of them influencing health and disease or cancer effects. Currently, effectiveness, safety, and practicability of different forms of fasting to fight cancer, particularly colorectal cancer, should still be contemplated with caution. KEYWORDS: colorectal cancer models; energy restriction; metabolism
  13. Lifestyle Factors and Risk of Myeloproliferative Neoplasms in the NIH-AARP Diet and Health Study. Podoltsev NA, Wang X, Wang R, Hofmann JN, Liao LM, Zeidan AM, Mesa R, Ma X. Int J Cancer. 2020 Jan 6. doi: 10.1002/ijc.32853. [Epub ahead of print] PMID: 31904114 https://sci-hub.tw/10.1002/ijc.32853 Abstract The etiology of Philadelphia chromosome negative myeloproliferative neoplasms (MPN) is largely unknown. We assessed potential associations between lifestyle factors and MPN risk in the NIH-AARP Diet and Health Study. In this prospective cohort with 463,049 participants aged 50-71 years at baseline (1995-1996) and a median follow-up of 15.5 years, we identified 490 MPN cases, including 190 with polycythemia vera (PV) and 146 with essential thrombocythemia (ET). Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking was not associated with MPN risk in the overall cohort, but analyses stratified by sex suggested that smoking increased the risk of MPN in women (former smoker vs. non-smokers, HR=1.43, 95% CI: 1.03-2.00, p=0.03; current smokers vs. non-smokers, HR=1.71, 95% CI: 1.08-2.71, p=0.02). Coffee consumption was inversely associated with the risk of PV (high vs. low intake, HR=0.53, 95% CI: 0.33-0.84, p-trend<0.01), but not the risk of ET or MPN overall. Further analysis revealed an inverse association between amount of caffeine intake and PV risk (high vs. low intake, HR= 0.55, 95% CI: 0.39-0.79, p-trend<0.01). While the consumption of caffeinated coffee appeared to confer a protective effect against PV, the consumption of decaffeinated coffee did not. This large prospective study identified smoking as a risk factor for MPN in women and suggests that caffeine intake is associated with a lower risk of PV. This article is protected by copyright. All rights reserved. KEYWORDS: epidemiology; lifestyle factors; myeloproliferative neoplasms PMID: 31904114 DOI: 10.1002/ijc.32853 Egg consumption and risk of coronary artery disease in the Million Veteran Program. Djoussé L, Ho YL, Nguyen XT, Quaden RM, Gagnon DR, Gaziano JM, Cho K. Clin Nutr. 2019 Dec 24. pii: S0261-5614(19)33203-0. doi: 10.1016/j.clnu.2019.12.017. [Epub ahead of print] PMID: 31902601 Abstract BACKGROUND & AIMS: Limited and inconsistent data are available on the relation between egg consumption and risk of myocardial infarction (MI) and it is unclear if adiposity or type 2 diabetes modifies egg-MI relation. We tested the primary hypothesis that egg consumption is positively associated with incidence of MI among veterans. In secondary analyses, we examined potential effect modification of egg-MI relation by adiposity and type 2 diabetes. METHODS: We analyzed data collected on 188,267 US veterans who were enrolled in the Million Veteran Program (MVP) from 2011 to 2018. Information on egg consumption was obtained via self-administered food frequency questionnaire and we used electronic health records to identify incident MI. RESULTS: The mean age was 64.4 (SD = 12.0) years and 9.9% of the population were female. We ascertained 10,260 new cases of non-fatal MI during an average follow up of 3.24 years (range: 0.002 to 7.49 y). Hazard ratio (95% CI) for non-fatal MI were 1.00 (ref), 0.93 (0.85-0.1.02), 0.96 (0.87-1.05), 0.98 (0.89-1.07), 1.08 (0.98-1.19), 1.11 (1.00-1.24), and 1.13 (1.00-1.28) for egg consumption of <1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, 1/d, and 2+/d, respectively, controlling for age, sex, race, body mass index, smoking, exercise, alcohol intake, and overall dietary pattern (p non-linear trend 0.019). In secondary analyses, we observed similar results with a composite endpoint including fatal MI, coronary angioplasty and revascularization. CONCLUSIONS: Our data showed no association of infrequent consumption of eggs with non-fatal MI but a slightly elevated risk with intake of 1 or more eggs per day among US veterans. KEYWORDS: Coronary artery disease; Diet; Epidemiology; Risk factors Midlife Modifiable Risk Factors for Dementia: A Systematic Review and Meta-analysis of 34 Prospective Cohort Studies. Li XY, Zhang M, Xu W, Li JQ, Cao XP, Yu JT, Tan L. Curr Alzheimer Res. 2020 Jan 2. doi: 10.2174/1567205017666200103111253. [Epub ahead of print] PMID: 31902364 Abstract OBJECTIVE: The aim of this study is to assess the association between midlife risk factors and dementia. METHODS: PubMed and Cochrane library were systematically searched on May 24, 2018, to retrieve prospective cohort studies. The summary relative risk (RR) and 95% confidence interval (CI) were calculated by the random-effect model to explore the association between midlife risk factors and dementia. Sensitivity analysis and meta-regression were conducted to explore the source of heterogeneity. Publication bias was examined using Begg's and Egger's tests. RESULTS: Thirty-four prospective cohort studies were included, among which 24 were eligible for meta-analysis. A total of 159,594 non-demented adults were enrolled at baseline before 65 years and 13,540 people were diagnosed with dementia after follow-up. The pooled results revealed that five factors could significantly increase the dementia risk by 41 to 78%, including obesity (RR, 1.78; 95% CI: 1.31-2.41), diabetes mellitus (RR, 1.69; 95% CI: 1.38-2.07), current smoking (RR, 1.61; 95%, CI: 1.32-1.95), hypercholesterolemia (RR, 1.57; 95% CI: 1.19-2.07), and hypertension (borderline blood pressure RR, 1.41; 95% CI: 1.23-1.62 and high systolic blood pressure (SBP) RR, 1.72; 95% CI: 1.25-2.37). However, the sensitivity analyses found that the results of hypercholesterolemia and high SBP were not reliable, which need to be confirmed by more high-quality studies. No influences due to publication bias were revealed. In the systematic review, another three factors (hyperhomocysteinemia, psychological stress, and heavy drinking) were found to be associated with elevated dementia risk. In addition, physical exercise, a healthy diet, and hormone therapy in middle age were associated with the reduction of dementia risk. CONCLUSIONS: Middle-aged people with obesity, diabetes, hypertension, or hypercholesterolemia, and current smokers in midlife are at higher risk of developing dementia later in life. KEYWORDS: Dementia; Meta-analysis; Midlife risk factors; Prospective Cohort Studies; Subgroup analyses; Systematic review Effect of Time Restricted Feeding on Metabolic Risk and Circadian Rhythm Associated with Gut Microbiome in Healthy Males. Zeb F, Wu X, Chen L, Fatima S, Haq IU, Chen A, Majeed F, Feng Q, Li M. Br J Nutr. 2020 Jan 6:1-25. doi: 10.1017/S0007114519003428. [Epub ahead of print] PMID: 31902372 https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A8C3BF83CBE5BF9CAC65ED783FA0FFD2/S0007114519003428a.pdf/div-class-title-effect-of-time-restricted-feeding-on-metabolic-risk-and-circadian-rhythm-associated-with-gut-microbiome-in-healthy-males-div.pdf Abstract Time restricted feeding (TRF) confer protection against nutritional challenges that predispose obesity and metabolic risks through involvement of clock genes and gut microbiome, but the underline mechanism is not clearly understood. Therefore, this study examined the effects of TRF on metabolic markers and circadian rhythm associated with gut microbiota in healthy males. Two groups (TRF, n=56; Non-TRF, n=24) of male adults were enrolled. TRF group provided blood at Pre-TRF and Post-TRF, while Non-TRF one time after 25 days of trial. Serum lipid and liver profiles were determined. RT-PCR was applied for circadian and inflammatory genes expression. The 16S rRNA gene were sequenced at Illumina Miseq v3 platform to comprehensively catalogue the composition and abundance of bacteria in stool. We showed that TRF ameliorated the serum lipid and liver profiles of the individuals. In TRF group, gut microbial richness was significantly enhanced, with enrichment of the Prevotellaceae and Bacteroideaceae. TRF enhanced circadian genes expression probably by activation of Sirt1, which is positively associated with gut microbiome richness. TRF could be a safe remedy for the prevention of metabolic diseases related to dyslipidemia, while regulates circadian rhythm associated with gut microbiome modulation. KEYWORDS: Circadian rhythm; Gut microbiome; Lipid profile; Metabolic risk; Time restricted feeding A word of caution against excessive protein intake. Mittendorfer B, Klein S, Fontana L. Nat Rev Endocrinol. 2020 Jan;16(1):59-66. doi: 10.1038/s41574-019-0274-7. Epub 2019 Nov 14. Review. PMID: 31728051 https://sci-hub.tw/10.1038/s41574-019-0274-7 https://sci-hub.tw/10.1038/s41574-019-0274-7 Abstract Dietary protein is crucial for human health because it provides essential amino acids for protein synthesis. In addition, dietary protein is more satiating than carbohydrate and fat. Accordingly, many people consider the protein content when purchasing food and beverages and report 'trying to eat more protein'. The global market for protein ingredients is projected to reach approximately US$90 billion by 2021, largely driven by the growing demand for protein-fortified food products. This Perspective serves as a caution against the trend of protein-enriched diets and provides an evidence-based counterpoint that underscores the potential adverse public health consequences of high protein intake. Japanese woman turns 117 years old, extends record as world's oldest person Kane Tanaka, born in 1903, lives in nursing home in southern Japan CBC News · Posted: Jan 05, 2020 7:01 AM ET | Last Updated: 5 hours ago https://www.cbc.ca/news/world/worlds-oldest-person-japan-1.5415517 Diet and Lifestyle in Prostate Cancer. Wilson KM, Mucci LA. Adv Exp Med Biol. 2019;1210:1-27. doi: 10.1007/978-3-030-32656-2_1. Abstract A variety of diet and lifestyle factors have been studied with respect to prostate cancer risk in large, prospective cohort studies. In spite of this work, and in contrast to other common cancers, few modifiable risk factors have been firmly established as playing a role in prostate cancer. There are several possible explanations for the lack of well-established risk factors. First, prostate cancer has among the highest heritability of all common cancers; second, early life exposures may play an important role in risk, rather than mid- and later-life exposures assessed in most epidemiological studies. Finally, prostate-specific antigen (PSA) screening plays a critical role in prostate cancer detection and incidence rates, which has important implications for epidemiological studies.Among modifiable risk factors, smoking and obesity are consistently associated with higher risk specifically of advanced prostate cancer. There is also considerable evidence for a positive association between dairy intake and overall prostate cancer risk, and an inverse association between cooked tomato/lycopene intake and risk of advanced disease. Several other dietary factors consistently associated with risk in observational studies, including selenium and vitamin E, have been cast into doubt by results from clinical trials. Results for other well-studied dietary factors, including fat intake, red meat, fish, vitamin D, soy and phytoestrogens are mixed.In practical terms, men concerned with prostate cancer risk should be encouraged to stop smoking, be as physically active as possible, and achieve or maintain a healthy weight. These recommendations also have the advantage of having a positive impact on risk of type 2 diabetes, cardiovascular disease, and other chronic diseases. Reducing dairy intake while increasing consumption of fish and tomato products is also reasonable advice.PMID: 31900902
  14. Effect of Flaxseed Supplementation on Lipid Profile: An Updated Systematic Review and Dose-Response Meta-Analysis of Sixty-Two Randomized Controlled Trials. Hadi A, Askarpour M, Salamat S, Ghaedi E, Symonds ME, Miraghajani M. Pharmacol Res. 2019 Dec 30:104622. doi: 10.1016/j.phrs.2019.104622. [Epub ahead of print] Review. PMID: 31899314 Abstract Raised plasma lipids are one the most important risk factors for cardiovascular disease. Flaxseed contains considerable amounts of α-linolenic acid, phenolic compounds, and lignans, which each have the capacity to reduce circulating lipid concentrations. This study aimed to systematically review current evidence to identify the potential effects of flaxseed supplementation on blood lipid profiles using a meta-analysis of randomized controlled trials (RCTs). PubMed, Scopus, Web of Science, and Google Scholar databases were searched for publications between January 1900 and May 2019. Weighted mean differences (WMDs) were analyzed using a random-effects model. The Cochrane Collaboration tool was also used to assess the risk of bias of the studies included. Sixty-two RCTs with a total of 3772 participants met the eligibility criteria. Our analysis showed that flaxseed supplementation significantly reduced total cholesterol (TC) (WMD = -5.389 mg/dL; 95% CI: -9.483, -1.295, p =  0.010), triglyceride (TG) (WMD = -9.422 mg/dL; 95% CI: -15.514, -3.330, p =  0.002), and low-density lipoprotein cholesterol (LDL-C) (WMD = -4.206 mg/dl; 95% CI: -7.260, -1.151, p =  0.007) concentrations. However, it had no effects on high-density lipoprotein cholesterol (WMD = 0.047 mg/dl; 95% CI: -0.777, 0.872, p = 0.910). This meta-analysis suggested that flaxseed supplementation improves serum TC, TG, and LDL-C, which could delay the progression of heart disease. Further studies with large-scale and better design are now needed to confirm these results. KEYWORDS: flaxseed; linseed; lipid profile; meta-analysis; systematic review Lactalbumin, Not Collagen, Augments Muscle Protein Synthesis with Aerobic Exercise. Oikawa SY, MacInnis MJ, Tripp TR, McGlory C, Baker SK, Phillips SM. Med Sci Sports Exerc. 2019 Dec 31. doi: 10.1249/MSS.0000000000002253. [Epub ahead of print] PMID: 31895298 Abstract INTRODUCTION: Protein ingestion and the ensuing hyperaminoacidemia stimulates skeletal muscle protein synthesis (MPS) in the post-exercise period. This response facilitates muscle remodeling, which is important during intensified training. The aim of this study was to determine whether supplementation with α-Lactalbumin (LA), with high leucine and tryptophan contents, would improve responses to short periods of intensified aerobic training compared to supplementation with an isonitrogenous quantity of collagen peptides (CP). METHODS: Endurance trained participants (5M, 6F, 24 ± 4 years, V[Combining Dot Above]O2= 53.2 ± 9.1 ml/kg/min, Peak power output (PPO) = 320 ± 48 W; means ± SD) consumed a controlled diet (1.0 g/kg/day protein) and refrained from habitual training for 11 days while taking part in this double-blind randomized, crossover trial. The two intervention phases, which consisted of brief intensified training (4×4-min cycling intervals at 70% of PPO on 3 consecutive days) combined with the ingestion of LA or CP supplements post-exercise (20g) and pre-sleep (40g), were separated by 4d of washout without protein supplementation (i.e., the control phase). In response to each phase, myofibrillar (MyoPS), sarcoplasmic protein synthesis (SarcPS) rates (via H2O ingestion) and parameters of sleep quality were measured. RESULTS: LA ingestion increased plasma leucine (p<0.001) and tryptophan concentrations (p<0.001) relative to CP. Intensified training increased MyoPS and SarcPS above the washout phase in LA- and CP- supplemented phases (p<0.01), with increases being 13 ± 5% and 5 ± 7% greater with LA than CP for MyoPS (p<0.01) and SarcPS, respectively (p<0.01). CONCLUSIONS: Despite an isonitrogenous diet, MPS was enhanced to a greater extent when trained participants consumed LA compared to CP during intensified aerobic training, suggesting protein quality is an important consideration for endurance-trained athletes aiming to augment adaption to exercise training. Testosterone administration during energy deficit suppresses hepcidin and increases iron availability for erythropoiesis. Hennigar SR, Berryman CE, Harris MN, Karl JP, Lieberman HR, McClung JP, Rood JC, Pasiakos SM. J Clin Endocrinol Metab. 2020 Jan 2. pii: dgz316. doi: 10.1210/clinem/dgz316. [Epub ahead of print] PMID: 31894236 https://watermark.silverchair.com/dgz316.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAnIwggJuBgkqhkiG9w0BBwagggJfMIICWwIBADCCAlQGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM__UZdlkaN6RzJQSBAgEQgIICJV02DEFTE0tBbnMtAHK8OtuQac6M3H5DmhqFBQcHLlM1Lv3WkcgtQF2Lp36SeGoFr-ml1ahALMDvUwA3HmJQudsBQfdWAivN1fK5kwOpT00pZM-5-4ZaqRRtxVkEzj7OD_TO1O9nhAJItwdPEhyHpcEWCH0lRAywHjgS1jxzoEPigRp0ohNzk0CEpMtnMP0Cr5nKemXHpxfGX3s5XAQgH2zVDhx67hXsEsCqhwJqdRJD-xAO4EXX7VzeKTBXcPE7ADi_9UmSqgKBjAcsY9hsxgR3ws_Kx8FC3y4YHNdlNEZZr0yousPluJn7GXZMzyyeSz6NCk7atYb6psxQL-7OClJPbF411kP0EG0sHYqec0t2PhlJ8OyT63MVw1ZVN5iUxHPWR-Ju8xJrKf8mgeoMWGYvFwZidfDOCgPpm6_elkdELECNlqCPqxOkZyTH-QrqkliwChZ9h1KSQcZ1lpgHkF5wglbly7uTtVJ2vzMSANJr39HXts3Ewugq3HYKYMQBhZMolhTi86z3iuM1RWI4R6Xr0SYOvqT1kVmEur6PofK3lc4lZOUdqOfjTuWfJVvjj6mAhlvhHM21df1SS1c5-TGC3q2gBZMY-HJL8l2oLU4hdvAVDLH5ISca4BXZVhEzc-tXIHUoSnRZaUomBdV3STPJeH6RgBy1ctvq3hQa0kvTMK6coz1dEYC4Z42ZhbuAVjWKtko89Xo-Xho2TwOf6W7StOLaFQ Abstract CONTEXT: Severe energy deprivation markedly inhibits erythropoiesis by restricting iron availability for hemoglobin synthesis. OBJECTIVE: The objective of this study was to determine whether testosterone supplementation during energy deficit increased indicators of iron turnover and attenuated the decline in erythropoiesis compared to placebo. DESIGN: This was a 3-phase, randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at the Pennington Biomedical Research Center. PATIENTS OR OTHER PARTICIPANTS: Fifty healthy young males. INTERVENTION(S): Phase 1 was a 14-d free-living, eucaloric controlled-feeding phase; phase 2 was a 28-d inpatient phase were participants were randomized to 200 mg testosterone enanthate/week or an isovolumetric placebo/week during an energy deficit of 55% of total daily energy expenditure; phase 3 was a 14-d free-living, ad libitum recovery period. MAIN OUTCOME MEASURE(S): Indices of erythropoiesis, iron status, and hepcidin and erythroferrone were determined. RESULTS: Hepcidin declined by 41%, indicators of iron turnover increased, and functional iron stores were reduced with testosterone administration during energy deficit compared to placebo. Testosterone administration during energy deficit increased circulating concentrations of erythropoietin and maintained erythropoiesis, as indicated by an attenuation in the decline in hemoglobin and hematocrit with placebo. Erythroferrone did no differ between groups, suggesting that the reduction in hepcidin with testosterone occurs through an erythroferrone-independent mechanism. CONCLUSIONS: These findings indicate that testosterone suppresses hepcidin, through either direct or indirect mechanisms, to increase iron turnover and maintain erythropoiesis during severe energy deficit. KEYWORDS: erythropoiesis; hepcidin; iron; testosterone
  15. Longitudinal and nonlinear relations of dietary and Serum cholesterol in midlife with cognitive decline: results from EMCOA study. An Y, Zhang X, Wang Y, Wang Y, Liu W, Wang T, Qin Z, Xiao R. Mol Neurodegener. 2019 Dec 30;14(1):51. doi: 10.1186/s13024-019-0353-1. PMID: 31888696 https://molecularneurodegeneration.biomedcentral.com/track/pdf/10.1186/s13024-019-0353-1 Abstract BACKGROUND: Previous studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. We thus investigated whether dietary and blood cholesterol were associated with cognitive decline. METHODS: Participants were drawn from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer's disease (EMCOA) study. We included 2514 participants who completed a selection of comprehensive cognitive tests and were followed for an average of 2.3 years. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were assessed and dietary intakes were investigated by food frequency questionnaire (FFQ) at baseline. Apolipoprotein E (APOE) was genotyped by Kompetitive Allele Specific PCR (KASP) sequencing. Non-high-density lipoprotein cholesterol (Non-HDL-C) and LDL-C/HDL-C ratio were calculated. The longitudinal effects of dietary and blood cholesterol on risk of global cognitive decline (decrease in Montreal Cognitive Assessment (MoCA) > 2 points) were examined using Cox proportional hazards models. The nonlinear associations with global and domain-specific cognitive decline was evaluated with mixed effect linear models. RESULTS: In Cox proportional hazards models, neither cholesterol nor egg intake was associated with a higher risk of accelerated global cognitive decline. In contrast, the higher serum concentrations of TC, LDL-C, non-HDL-C and LDL-C/HDL-C ratio were positively associated with accelerated global cognitive decline regardless of being evaluated continuously or categorically while higher HDL-C was positively associated with accelerated global cognitive decline only when being evaluated categorically (all P < 0.05). In mixed effect linear models, quadratic and longitudinal relations of dietary cholesterol and egg intakes to global cognition, processing speed and executive function were observed. Moreover, there were inverted U-shaped relations of HDL-C, with processing speed and executive function but U-shaped relations of HDL-C and LDL-C/HDL-C ratio with verbal memory. Adverse linear associations of higher LDL-C and LDL-C/HDL-C ratio with multiple cognitive comes were also revealed. Additionally adjusting for APOE genotype did not modify cholesterol-cognition associations. Dietary and serum cholesterol had variable associations with global and domain-specific cognitive decline across educational groups. CONCLUSION: Differential associations between dietary/serum cholesterol and cognitive decline across different domains of function were observed in a particular population of middle-aged and elderly Chinese. Interventions to improve cognitive reserve regarding dietary instruction and lipid management should be tailored according to specific target. KEYWORDS: Cholesterol; Cognitive decline; Nonlinear Impact of calcium, vitamin D, vitamin K, oestrogen, isoflavone and exercise on bone mineral density for osteoporosis prevention in postmenopausal women: a network meta-analysis Zijun Xu, Huwen Wang, Yue Shi, Qiuming Shen, Lhakpa Tsamlag, Zezhou Wang, Shoukai Yu, Tian Shen, Ying Wang, Yong Cai British Journal of Nutrition, Volume 123 / Issue 1, 14 January 2020, pp 84 - 103 doi: 10.1017/S0007114519002290 Published Online on 4 September 2019 Abstract The aim of this network meta-analysis is to compare bone mineral density (BMD) changes among different osteoporosis prevention interventions in postmenopausal women. We searched MEDLINE, Embase and Cochrane Library from inception to 24 February 2019. Included studies were randomised controlled trials (RCT) comparing the effects of different treatments on BMD in postmenopausal women. Studies were independently screened by six authors in three pairs. Data were extracted independently by two authors and synthesised using Bayesian random-effects network meta-analysis. The results were summarised as mean difference in BMD and surface under the cumulative ranking (SUCRA) of different interventions. A total of ninety RCT (10 777 participants) were included. Ca, vitamin D, vitamin K, oestrogen, exercise, Ca + vitamin D, vitamin D + vitamin K and vitamin D + oestrogen were associated with significantly beneficial effects relative to no treatment or placebo for lumbar spine (LS). For femoral neck (FN), Ca, exercise and vitamin D + oestrogen were associated with significantly beneficial intervention effects relative to no treatment. Ranking probabilities indicated that oestrogen + vitamin D is the best strategy in LS, with a SUCRA of 97·29 % (mean difference: +0·072 g/cm2 compared with no treatment, 95 % credible interval (CrI) 0·045, 0·100 g/cm2), and Ca + exercise is the best strategy in FN, with a SUCRA of 79·71 % (mean difference: +0·029 g/cm2 compared with placebo, 95 % CrI –0·00093, 0·060 g/cm2). In conclusion, in postmenopausal women, many interventions are valuable for improving BMD in LS and FN. Different intervention combinations can affect BMD at different sites diversely. Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials. Yang HH, Li XL, Zhang WG, Figueroa A, Chen LH, Qin LQ. Nutr Metab (Lond). 2019 Dec 26;16:89. doi: 10.1186/s12986-019-0415-y. eCollection 2019. Review. PMID: 31889969 Abstract BACKGROUND: Experimental evidence indicates that oral L-citrulline (L-Cit) may reduce resting blood pressure (BP) as well as BP responses to exercise and cold exposure (non-resting). However, results from human intervention trials are inconsistent. This study aims to summarize the clinical evidence regarding the effects of L-Cit supplementation on brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), in addition to aortic SBP and aortic DBP at rest and non-resting conditions. METHODS: Multiple databases including PubMed, Embase, Cochrane library, Web of Science, and Clinical Trials were searched systematically. Randomized controlled trials of human participants were quantitatively meta-analyzed. RESULTS: Fourteen trials contained in eight studies were available for quantitative syntheses for brachial BP. Results showed that L-Cit supplementation significantly reduced both brachial SBP (- 4.490 mmHg, 95% CI: - 7.332 to - 1.648, P = 0.002) and brachial DBP (- 3.629 mmHg, 95% CI: - 5.825 to - 1.434, P = 0.001). Nine of the trials were meta-analyzed for aortic BP which showed that L-Cit intervention significantly reduced aortic SBP (- 6.763 mmHg, 95% CI: - 10.991 to - 2.534, P = 0.002), but not aortic DBP (- 3.396 mmHg, 95% CI: - 7.418 to 0.627, P = 0.098). The observed reducing effects of L-Cit appeared stronger for non-resting than for resting brachial SBP (P for difference = 0.044). CONCLUSION: L-Cit supplementation significantly decreased non-resting brachial and aortic SBP. Brachial DBP was significantly lowered by L-Cit regardless of resting status. Given the relatively small number of available trials in the stratified analyses and the potential limitations of these trials, the present findings should be interpreted cautiously and need to be confirmed in future well-designed trials with a larger sample size. KEYWORDS: Aortic; Blood pressure; Brachial; L-citrulline; Resting status Effect of selenium supplementation on glycemic indices: a meta-analysis of randomized controlled trials. Mahdavi Gorabi A, Hasani M, Djalalinia S, Zarei M, Ejtahed H, Abdar ME, Asayesh H, Azimzadeh M, Qorbani M, Noroozi M. J Diabetes Metab Disord. 2019 Jul 4;18(2):349-362. doi: 10.1007/s40200-019-00419-w. eCollection 2019 Dec. PMID: 31890660 Abstract PURPOSE: The association between selenium supplementation and glycemic indices seems to be a controversial issue. This systematic review and meta-analysis was conducted to evaluate the effect of selenium supplementation on glycemic indices. METHODS: We systematically searched PubMed/MEDLINE, ISI/WOS, and Scopus (from their commencements up to Jan 2016) for relevant studies examining the association between intake of selenium and glycemic indices. The data were extracted from relevant qualified studies and estimated using the random-effect or pooled model and standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Twelve articles published between 2004 and 2016 were included. In all the studies, the participants were randomly assigned to an intervention group (n = 757) or a control group(n = 684). All the studies were double blind, placebo controlled trials. Selenium supplementation resulted in a significant decrease in homeostasis model of assessment-estimated β-cell function (HOMA-B) (SMD: -0.63; 95%CI: -0.89 to -0.38) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (SMD: by 0.74; 95%CI: 0.49 to 0.1) as compared with the controls. There were no statistically significant improvements in glycemic indices, such as fasting plasma glucose (FPG), insulin, homeostasis model of assessment-estimated insulin resistance (HOMA-IR), Hemoglobin A1c (HbA1c) and adiponectin. CONCLUSION: This meta-analysis indicated that selenium supplementation significantly decreased HOMA-B and increased QUICKI score. There was no statistically significant improvement in FPG, insulin, HOMA-IR, HbA1c and adiponectin indices following selenium supplementation. KEYWORDS: FPG; Glycemic indices; HbA1c; Insulin; Selenium