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  1. Metabolomics identifies increases in the acylcarnitine profiles in the plasma of overweight subjects in response to mild weight loss: a randomized, controlled design study. Kang M, Yoo HJ, Kim M, Kim M, Lee JH. Lipids Health Dis. 2018 Oct 15;17(1):237. doi: 10.1186/s12944-018-0887-1. PMID: 30322392 https://lipidworld.biomedcentral.com/track/pdf/10.1186/s12944-018-0887-1 Abstract BACKGROUND: Using metabolomics technique to analyze the response to a dietary intervention generates valuable information concerning the effects of the prescribed diet on metabolic regulation. To determine whether low calorie diet (LCD)-induced weight reduction causes changes in plasma metabolites and metabolic characteristics. METHODS: Overweight subjects consumed a LCD (n = 47) or a weight maintenance diet (control, n = 50) in a randomized, controlled design study with a 12-week clinical intervention period. Plasma samples were analyzed using an UPLC-LTQ-Orbitrap MS. RESULTS: The 12-week LCD intervention resulted in significant mild weight loss, with an 8.3% and 10.6% reduction observed in the visceral fat area (VFA) at the level of the lumbar vertebrae L1 and L4, respectively. The LCD group showed a significant increase in the mean change of serum free fatty acids compared to the control group. In the LCD group, we observed a significant increase in the acylcarnitine (AC) levels, including hexanoylcarnitine, L-octanoylcarnitine, 9-decenoylcarnitine, trans-2-dodecenoylcanitine, dodecanoylcarnitine, 3,5-tetradecadiencarnitine, cis-5-tetradecenoylcarnitine, 9,12-hexadecadienoylcarnitine, and 9-hexadecenoylcarnitne at the 12-week follow-up assessment. When the plasma metabolite changes from baseline were compared between the control and LCD groups, the LCD group showed significant increases in hexanoylcarnitine, L-octanoylcarnitine, trans-2-dodecenoylcanitine, and 3,5-tetradecadiencarnitine than the control group. Additionally, the changes in these ACs in the LCD group strongly negatively correlated with the changes in the VFA at L1 and/or L4. CONCLUSION: Mild weight loss from 12-week calorie restriction increased the plasma levels of medium- and long-chain ACs. These changes were coupled with a decrease in VFA and an increase in free fatty acids. KEYWORDS: Acylcarnitine; Low calorie diet; Metabolomics; Mild weight loss; Visceral fat area Social Isolation and Mortality in US Black and White Men and Women. Alcaraz KI, Eddens KS, Blase JL, Diver WR, Patel AV, Teras LR, Stevens VL, Jacobs EJ, Gapstur SM. Am J Epidemiol. 2018 Oct 16. doi: 10.1093/aje/kwy231. [Epub ahead of print] PMID: 30325407 Abstract Social isolation is associated with higher mortality in studies of mostly white adults, yet associations among black adults is unclear. This prospective cohort study evaluated whether associations of social isolation with all-cause, cardiovascular disease and cancer mortality differ by race and sex. Adults enrolled into Cancer Prevention Study-II in 1982/1983 were followed for mortality through 2012 (n = 580,182). Sex- and race-specific multivariable-adjusted hazard ratios and 95% confidence intervals were estimated for associations of a five-point social isolation score with risk of death. Social isolation was associated with all-cause mortality in all subgroups (P-trend ≤ 0.005); for the most versus the least isolated, the hazard ratios (95% confidence intervals) were 2.34 (1.58, 3.46) and 1.60 (1.41, 1.82) among black and white men, respectively (P-interaction = 0.40), and 2.13 (1.44, 3.15) and 1.84 (1.68, 2.01) among black and white women, respectively (P-interaction = 0.89). The association did not differ between black men and women (P-interaction = 0.33) but was slightly stronger in white women than white men (P-interaction = 0.01). Social isolation was associated with cardiovascular disease mortality in each subgroup (P-trend < 0.03) but with cancer mortality only among whites (P-trend < 0.0001). Subgroup differences in the influence of specific social isolation components were identified. Identifying and intervening with socially isolated adults could improve health outcomes. An association of urinary sodium-potassium ratio with insulin resistance among Korean adults. Park YM, Kwock CK, Park S, Eicher-Miller HA, Yang YJ. Nutr Res Pract. 2018 Oct;12(5):443-448. doi: 10.4162/nrp.2018.12.5.443. Epub 2018 Sep 28. PMID: 30323912 Abstract BACKGROUND/OBJECTIVES: This study was conducted to investigate the effects of sodium-potassium ratio on insulin resistance and sensitivity in Korean adults. SUBJECTS/METHODS: Subjects were 3,722 adults (1,632 men and 2,090 women) aged 40-69 years participating in the Korean genome and epidemiology study_Ansan and Ansung study. Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HoMA-IR) and fasting insulin, and insulin sensitivity was assessed by using the quantitative insulin sensitivity check index (QUICKI). The 24-h urinary sodium and potassium excretion were estimated from spot urinary samples using the Tanaka formula. The generalized linear model was applied to determine the association between urinary sodium-potassium ratio and insulin resistance. RESULTS: HoMA-IR (P-value = 0.029, P-trend = 0.008) and fasting insulin (P-value = 0.017, P-trend = 0.005) levels were positively associated with 24-h estimated urinary sodium-potassium ratio in the multivariable model. QUICKI was inversely associated with 24-h estimated urinary sodium-potassium ratio in all models (P-value = 0.0002, P-trend < 0.0001 in the multivariate model). CONCLUSION: The present study suggests that high sodium-potassium ratio is related to high insulin resistance and low insulin sensitivity. Decreasing sodium intake and increasing potassium intake are important for maintaining insulin sensitivity. Further studies are needed to confirm these findings in longitudinal studies. KEYWORDS: Sodium; insulin resistance; insulin sensitivity; potassium Physical Activity and Association Between Frailty and All-Cause and Cardiovascular Mortality in Older Adults: Population-Based Prospective Cohort Study. Higueras-Fresnillo S, Cabanas-Sánchez V, Lopez-Garcia E, Esteban-Cornejo I, Banegas JR, Sadarangani KP, Rodríguez-Artalejo F, Martinez-Gomez D. J Am Geriatr Soc. 2018 Oct 16. doi: 10.1111/jgs.15542. [Epub ahead of print] PMID: 30325012 Abstract OBJECTIVES: To examine the separate and joint association between physical activity and frailty and long-term all-cause and cardiovascular disease (CVD) mortality in older adults. DESIGN: Population-based prospective cohort study. SETTING: Cohort representative of the noninstitutionalized Spanish population. PARTICIPANTS: Individuals aged 60 and older (N=3,896) in 2000-01. MEASUREMENTS: Participants reported their physical activity using a validated instrument, and frailty was ascertained using the Fatigue, low Resistance, limitation in Ambulation, Illness and weight Loss (FRAIL) scale. Those with 0 frailty criteria were considered to be robust, with 1 or 2 criteria to be prefrail, and with 3 of more criteria to be frail. Participants were followed until 2014 to identify all-cause and CVD deaths. Associations were summarized using hazard ratios (HRs) and Cox regression after adjustment for main covariates. RESULTS: During a median 14 years of follow-up, 1,801 total deaths occurred, 672 from CVD. Compared with being robust, the multivariate hazard ratio (95% confidence interval) for all-cause mortality was 1.29 (1.14-1.45) in prefrail individuals, and 2.16 (1.82-2.58) in frail individuals (p-trend <.001). Compared with being physically inactive, being physically active was associated with a statistically significant 18% (1-32%), 28% (16-39%) and 39% (17-55%) lower all-cause mortality among robust, prefrail, and frail individuals, respectively (all p <.001). Compared with participants who were robust and physically active, those who were frail and inactive showed the highest all-cause mortality 2.45 (95%CI: 1.95-3.06); however, the hazard ratio (95% confidence interval) for all-cause mortality in frail individuals who were physically active was comparable to that in pre-frail and inactive participants: 1.70 (1.32-2.19) and 1.56 (1.34-1.82), respectively. Mortality of prefrail active participants was similar to that of robust inactive participants. Results were similar for CVD mortality. CONCLUSION: Physical activity might partly compensate for the greater mortality risk associated with frailty in old age. KEYWORDS: elderly; frailty; mortality; physical activity Prolonging healthy aging: Longevity vitamins and proteins. Ames BN. Proc Natl Acad Sci U S A. 2018 Oct 15. pii: 201809045. doi: 10.1073/pnas.1809045115. [Epub ahead of print] PMID: 30322941 https://sci-hub.tw/10.1073/pnas.1809045115 Abstract It is proposed that proteins/enzymes be classified into two classes according to their essentiality for immediate survival/reproduction and their function in long-term health: that is, survival proteins versus longevity proteins. As proposed by the triage theory, a modest deficiency of one of the nutrients/cofactors triggers a built-in rationing mechanism that favors the proteins needed for immediate survival and reproduction (survival proteins) while sacrificing those needed to protect against future damage (longevity proteins). Impairment of the function of longevity proteins results in an insidious acceleration of the risk of diseases associated with aging. I also propose that nutrients required for the function of longevity proteins constitute a class of vitamins that are here named "longevity vitamins." I suggest that many such nutrients play a dual role for both survival and longevity. The evidence for classifying taurine as a conditional vitamin, and the following 10 compounds as putative longevity vitamins, is reviewed: the fungal antioxidant ergothioneine; the bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine; and the plant antioxidant carotenoids lutein, zeaxanthin, lycopene, α- and β-carotene, β-cryptoxanthin, and the marine carotenoid astaxanthin. Because nutrient deficiencies are highly prevalent in the United States (and elsewhere), appropriate supplementation and/or an improved diet could reduce much of the consequent risk of chronic disease and premature aging. KEYWORDS: aging; essential minerals; nutrition; vitamins A comparison of blood pressure indices as predictors of all-cause mortality among middle-aged men and women during 701,707 person-years of follow-up. Rosenblad A. J Hum Hypertens. 2018 Jul 10. doi: 10.1038/s41371-018-0085-7. [Epub ahead of print] PMID: 29991703 Abstract High systolic blood pressure (SBP) is often used as a measure of hypertension in epidemiological studies. Alternative blood pressure (BP) indices include diastolic blood pressure (DBP), pulse pressure (PP), mid-blood pressure (MBP) and mean arterial pressure (MAP). The present study compares the predictive ability for all-cause mortality (ACM) of these indices and the novel BP index mean proportional arterial pressure (MPAP), defined as the weighted mean of SBP and DBP where the weights are proportional to SBP's and DBP's contributions to the sum of SBP and DBP. Using a Swedish cohort of 32,238 middle-aged men and women, not being on antihypertensive treatment, examined in 1989-2000 and followed-up until March 9, 2017, the predictive abilities for ACM of SBP, DBP, PP, MBP, MAP and MPAP were compared using a likelihood-based R2-type measure for adjusted and unadjusted Cox regression models. Of the included participants (mean age 45.4 years, 48.2% men), 2936 (9.1%) died during a mean follow-up time of 21.8 years, equalling 701,707 person-years at risk. Higher BP were for all indices significantly associated with increased ACM. For all models, those including MPAP had the highest predictive ability, followed in turn by models including MBP, SBP, MAP, DBP and PP, respectively. The difference was significant for SBP, DBP and PP in unadjusted models and for PP in fully adjusted models. In conclusion, MPAP and MBP are the best predictors of ACM. Until the clinical usefulness of these indices has been evaluated, they may primarily be useful for epidemiological studies.
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    Hypocaloric Diet Prevents the Decrease in FGF21 Elicited by High Phosphorus Intake. Pineda C, Rios R, Raya AI, Rodriguez M, Aguilera-Tejero E, Lopez I. Nutrients. 2018 Oct 13;10(10). pii: E1496. doi: 10.3390/nu10101496. PMID: 30322116 https://www.mdpi.com/2072-6643/10/10/1496/htm Abstract The effect of dietary phosphorus (P) on fibroblast growth factor 21 (FGF21)/β-klotho axis was investigated in rats that were fed diets with: Normal (NP) or high P (HP) and either normal (NC), high (HC) or low calories (LC). Sampling was performed at 1, 4 and 7 months. Plasma FGF21 concentrations were higher (p < 0.05) in NC and HC than in LC groups. Increasing P intake had differing effects on plasma FGF21 in rats fed NC and HC vs. rats fed LC at the three sampling times. When compared with the NP groups, FGF21 concentrations decreased at the three sampling points in rats fed NC-HP (80 vs. 194, 185 vs. 382, 145 vs. 403 pg/mL) and HC-HP (90 vs. 190, 173 vs. 353, 94 vs. 434 pg/mL). However, FGF21 did not decrease in rats fed LC-HP (34 vs. 20, 332 vs. 164 and 155 vs. 81 pg/mL). In addition, LC groups had a much lower liver FGF21 messenger ribonucleic acid/glyceraldehyde 3-phosphate dehydrogenase (mRNA/GAPDH) ratio (0.51 ± 0.08 and 0.56 ± 0.07) than the NC-NP (0.97 ± 0.14) and HC-NP (0.97 ± 0.22) groups. Increasing P intake reduced liver FGF21 mRNA/GAPDH in rats fed NC and HC to 0.42 ± 0.05 and 0.37 ± 0.04. Liver β-klotho mRNA/GAPDH ratio was lower (p < 0.05) in LC groups (0.66 ± 0.06 and 0.59 ± 0.10) than in NC (1.09 ± 0.17 and 1.03 ± 0.14) and HC (1.19 ± 0.12 and 1.34 ± 0.19) groups. A reduction (p < 0.05) in β-klotho protein/α-tubulin ratio was also observed in LC groups (0.65 ± 0.05 and 0.49 ± 0.08) when compared with NC (1.12 ± 0.11 and 0.91 ± 0.11) and HC (0.93 ± 0.17 and 0.87 ± 0.09) groups. In conclusion β-klotho is potently regulated by caloric restriction but not by increasing P intake while FGF21 is regulated by both caloric restriction and increased P intake. Moreover, increased P intake has a differential effect on FGF21 in calorie repleted and calorie depleted rats. KEYWORDS: calories; fibroblast growth factor 21; phosphorus; rat
  3. Diabetes mellitus, blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies. Aune D, Schlesinger S, Neuenschwander M, Feng T, Janszky I, Norat T, Riboli E. Nutr Metab Cardiovasc Dis. 2018 Jul 25. pii: S0939-4753(18)30230-8. doi: 10.1016/j.numecd.2018.07.005. [Epub ahead of print] PMID: 30318112 Abstract BACKGROUND AND AIM: The strength of the association between diabetes and risk of heart failure has differed between previous studies and the available studies have not been summarized in a meta-analysis. We therefore quantified the association between diabetes and blood glucose and heart failure in a systematic review and meta-analysis. METHODS AND RESULTS: PubMed and Embase databases were searched up to May 3rd 2018. Prospective studies on diabetes mellitus or blood glucose and heart failure risk were included. A random effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). Seventy seven studies were included. Among the population-based prospective studies, the summary RR for individuals with diabetes vs. no diabetes was 2.06 (95% CIs: 1.73-2.46, I2 = 99.8%, n = 30 studies, 401495 cases, 21416780 participants). The summary RR was 1.23 (95% CI: 1.15-1.32, I2 = 78.2%, n = 10, 5344 cases, 91758 participants) per 20 mg/dl increase in blood glucose and there was evidence of a J-shaped association with nadir around 90 mg/dl and increased risk even within the pre-diabetic blood glucose range. Among the patient-based studies the summary RR was 1.69 (95% CI: 1.57-1.81, I2 = 85.5%, pheterogeneity<0.0001) for diabetes vs. no diabetes (n = 41, 100284 cases and >613925 participants) and 1.25 (95% CI: 0.89-1.75, I2 = 95.6%, pheterogeneity<0.0001) per 20 mg/dl increase in blood glucose (1016 cases, 34309 participants, n = 2). In the analyses of diabetes and heart failure there was low or no heterogeneity among the population-based studies that adjusted for alcohol intake and physical activity and among the patient-based studies there was no heterogeneity among studies with ≥10 years follow-up. CONCLUSIONS: These results suggest that individuals with diabetes are at an increased risk of developing heart failure and there is evidence of increased risk even within the pre-diabetic range of blood glucose. KEYWORDS: Blood glucose; Diabetes mellitus; Heart failure; Meta-analysis; Systematic review The Role of Lifestyle Factors and Sleep Duration for Late-Onset Dementia: A Cohort Study. Larsson SC, Wolk A. J Alzheimers Dis. 2018 Oct 3. doi: 10.3233/JAD-180529. [Epub ahead of print] PMID: 30320581 Abstract BACKGROUND: The role of lifestyle factors and sleep for dementia is uncertain. OBJECTIVE: To examine the associations of major lifestyle factors and sleep duration with risk of late-onset dementia. METHODS: We used data from a population-based cohort of 28,775 Swedish adults who were ≥65 years of age and completed a questionnaire about lifestyle and other modifiable factors in the autumn of 1997. Dementia cases were ascertained by linkage with the Swedish National Patient Register. RESULTS: During a mean follow-up of 12.6 years, dementia was diagnosed among 3,755 participants (mean age at diagnosis 83.2±5.1 years). There were no associations of an overall healthy diet (defined by a modified Dietary Approaches to Stop Hypertension Diet score or a Mediterranean diet score), alcohol and coffee consumption, or physical activity with dementia incidence. Compared with never smokers, dementia risk was increased in former and current smokers (hazard ratio [95% confidence interval] = 1.13 [1.04-1.23] and 1.10 [1.00-1.21], respectively). Extended time of sleep (>9 h per night) was associated with an increased risk of dementia. However, this association appeared to be related to a reverse causation effect since the association did not remain after exclusion of cases diagnosed within the first five or ten years of follow-up. CONCLUSIONS: This study found no evidence that major lifestyle factors, aside from smoking, or sleep duration influence the risk of dementia. KEYWORDS: Cohort studies; dementia; diet; lifestyle; prospective studies; sleep The effects of whole-grain compared with refined wheat, rice, and rye on the postprandial blood glucose response: a systematic review and meta-analysis of randomized controlled trials. Musa-Veloso K, Poon T, Harkness LS, O'Shea M, Chu Y. Am J Clin Nutr. 2018 Oct 1;108(4):759-774. doi: 10.1093/ajcn/nqy112. PMID: 30321274 https://sci-hub.tw/10.1093/ajcn/nqy112 Abstract BACKGROUND: Whole grains are often referred to collectively, despite differences in their composition, physical structure, processing, and potential health benefits. OBJECTIVE: The aim of this study was to compare the postprandial blood glucose response of whole-grain with refined wheat, rice, or rye, while controlling for the food delivery matrix and the processing of the grain (e.g., grinding, germination). DESIGN: Eleven electronic databases were systematically searched to identify studies published up to and including November 2017. Randomized controlled trials comparing the effects of whole-grain wheat, rice, or rye with those of each grain's refined counterpart on postprandial blood glucose area under the curve (AUC) were included. Pooled effect sizes were computed by using the difference in the blood glucose AUC after the consumption of the whole compared with the refined grain. RESULTS: Twenty publications were included, with 10, 14, and 5 strata (or active-control comparisons) on whole-grain wheat, rice, and rye, respectively. The consumption of ground (wholemeal) wheat, compared with white wheat, was not associated with a significant reduction in blood glucose AUC (-6.7 mmol/L ⋅ min; 95% CI: -25.1, 11.7 mmol/L ⋅ min; P = 0.477). The consumption of wholemeal rye, compared with endosperm rye, was not associated with a significant reduction in blood glucose AUC (-5.5 mmol/L ⋅ min; 95% CI: -24.8, 13.8 mmol/L ⋅ min; P = 0.576). The consumption of intact (whole-grain) rice, compared with white rice, was associated with a significant reduction in blood glucose AUC (-40.5 mmol/L ⋅ min; 95% CI: -59.6, -21.3 mmol/L ⋅ min; P < 0.001). CONCLUSIONS: Compared with white rice, whole-grain rice significantly attenuates the postprandial blood glucose response. In most of the studies on wheat and rye, the postprandial blood glucose responses to foods formulated with wholemeal compared with refined flours were compared. Whether reductions in the blood glucose AUC can be achieved with whole-grain (as opposed to wholemeal) wheat and rye requires further investigation.
  4. Protein malnutrition mitigates the effects of a high-fat diet on glucose homeostasis in mice. Branco RCS, Camargo RL, Batista TM, Vettorazzi JF, Lubaczeuski C, Bomfim LHM, Silveira LR, Boschero AC, Zoppi CC, Carneiro EM. J Cell Physiol. 2018 Oct 14. doi: 10.1002/jcp.27361. [Epub ahead of print] PMID: 30317568 Abstract Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation. KEYWORDS: fat-enriched diet; gastrocnemius; insulin sensitivity; protein restriction Major trauma and acceleration of the ageing process. Sullivan J, Mirbahai L, Lord JM. Ageing Res Rev. 2018 Oct 11. pii: S1568-1637(18)30187-9. doi: 10.1016/j.arr.2018.10.001. [Epub ahead of print] Review. PMID: 30316759 http://sci-hub.tw/http://www.sciencedirect.com/science/article/pii/S1568163718301879 Abstract It is well established that numerous factors can affect the rate at which we age biologically. Diet, physical activity, lifestyle and our genes all play a major role in influencing the ageing trajectory and longevity. Major trauma affects millions globally, is the major cause of death in young adults and could influence ageing processes but has largely been ignored by biogenterologists. The long-term health consequences of physical trauma are well known in the medical community, how trauma effects the ageing process at a molecular level is not. It has long been difficult to assess ageing trajectories due to the absence of a biomarker of biological rather than chronological age. Recent advances in epigenetics have helped by identifying specific DNA methylation sites as good indicators of biological age. Recent investigations into the impact of psychological trauma and the associated physical stress on accelerating ageing as measured by epigenetic drift are promising. The physical and metabolic stress which is synonymous with physical trauma may also accelerate the ageing process. We suggest that long term epigenetic profiling is required to understand to what degree the ageing trajectory is altered by trauma, which will in turn add support for the development of novel therapies to improve health outcomes for survivors of traumatic injury. KEYWORDS: DNA methylation; ageing; epigenetic; injury; trauma >>>>>>> [Don't drink and drive: https://www.archives-pmr.org/article/S0003-9993(13)00532-7/pdf .] Searching for longevity hotspots in Denmark. Hansen AV, Mortensen LH, Westendorp R. Aging (Albany NY). 2018 Oct 13. doi: 10.18632/aging.101579. [Epub ahead of print] PMID: 30317223 Abstract While existing research on regions with high prevalence of centenarians has focused on selected candidate geographical regions, we explore the existence of hotspots in the whole of Denmark.We performed a Kulldorff spatial scan, searching for regions of birth, and of residence at age 71, where an increased percentage of the cohort born 1906-1915 became centenarians. We then compared mortality hazards for these regions to the rest of the country.We found a birth hotspot of 222 centenarians, 1.37 times more than expected, centered on a group of rural islands. Lower mortality hazards from age 71 onwards were confined to those born within the hotspot and persisted over a period of at least 30 years. At age 71, we found two residence-based hotspots of 348 respectively 238 centenarians, 1.46 and 1.44 times the expected numbers. One hotspot, located in high-income suburbs of the Danish capital, seems driven by selective in-migration of low-mortality individuals. The other hotspot seems driven by selective migration and lower morality among those born and residing in the hotspot.Thus, Danish centenarian hotspots do exist. The locations and interpretation depend on whether we look at place of birth or of residence late in life. KEYWORDS: Denmark; centenarian rate; cluster detection; longevity Association between lifestyle risk factors and incident hypertension among middle-aged and older Australians. Nguyen B, Bauman A, Ding D. Prev Med. 2018 Oct 11. pii: S0091-7435(18)30312-8. doi: 10.1016/j.ypmed.2018.10.007. [Epub ahead of print] PMID: 30316880 Abstract This study aimed to examine the association between individual and combined lifestyle risk factors and the incidence of hypertension 1) in middle-aged and older Australians, and 2) to compare findings in men and women. A sample of 32,393 adults aged ≥45 years from New South Wales completed baseline (2006-2008) and follow-up (2010) questionnaires. Self-reported incident hypertension was defined as not having physician-diagnosed hypertension nor taking antihypertensive medications at baseline and reporting a diagnosis/treatment of hypertension at follow-up. High-risk categories for six lifestyle risk factors were defined as: a BMI ≥ 25 kg/m2, physical activity levels <150 min/week, consuming ≥14 alcohol drinks/week, being a current smoker, consuming <2 fruit and/or <3 vegetable serves/day, and being at high risk of psychological distress (Kessler-10 score ≥ 22). The association between baseline risk factors and incident hypertension was examined using logistic regression models, adjusted for socio-demographic, medical and lifestyle risk factors. After 2.7 (SD: 0.9) years of follow-up, 17.1% developed hypertension. Compared to low-risk categories, high BMI (AOR [95% CI]: 1.99 [1.85, 2.13]), high alcohol intake (1.58 [1.44, 1.73]), low physical activity levels (1.17 [1.07, 1.27]) and being a current smoker (1.15 [1.0, 1.31]) were associated with a higher incidence of hypertension in the overall sample, with similar associations in men and women. The number of high-risk lifestyle factors was positively associated with higher odds of developing hypertension in the overall sample, men and women; with a stronger association in middle-aged men. Adopting a low-risk lifestyle may prevent hypertension among middle-aged and older adults. KEYWORDS: Blood pressure; Hypertension; Lifestyle; Prospective studies; Risk factors Broccoli consumption affects the human gastrointestinal microbiota. Kaczmarek JL, Liu X, Charron CS, Novotny JA, Jeffery EH, Seifried HE, Ross SA, Miller MJ, Swanson KS, Holscher HD. J Nutr Biochem. 2018 Sep 21;63:27-34. doi: 10.1016/j.jnutbio.2018.09.015. [Epub ahead of print] PMID: 30317146 Abstract The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index <26 kg/m2, and within this group, there were associations between bacterial relative abundance and glucosinolate metabolites. Functional prediction revealed that broccoli consumption increased the pathways involved in the functions of the endocrine system (P=.05), transport and catabolism (P=.04), and energy metabolism (P=.01). These results reveal that broccoli consumption affects the composition and function of the human gastrointestinal microbiota. KEYWORDS: Bacteroides; Brassica vegetables; Cruciferous vegetables; Glucosinolates; Microbiome
  5. When scientists want their data fudged and why you should care Some statisticians have been asked to falsify significance of research results, new study finds Kelly Crowe · CBC News · Posted: Oct 13, 2018 https://www.cbc.ca/news/health/second-opinion-scientists-data-fudging-1.4861556 >>>>>>>>>>>>>>>>>> Researcher Requests for Inappropriate Analysis and Reporting: A U.S. Survey of Consulting Biostatisticians. Wang MQ, Yan AF, Katz RV. Ann Intern Med. 2018 Oct 9. doi: 10.7326/M18-1230. [Epub ahead of print] PMID: 30304365 Abstract BACKGROUND: Inappropriate analysis and reporting of biomedical research remain a problem despite advances in statistical methods and efforts to educate researchers. OBJECTIVE: To determine the frequency and severity of requests biostatisticians receive from researchers for inappropriate analysis and reporting of data during statistical consultations. DESIGN: Online survey. SETTING: United States. PARTICIPANTS: A randomly drawn sample of 522 American Statistical Association members self-identifying as consulting biostatisticians. MEASUREMENTS: The Bioethical Issues in Biostatistical Consulting Questionnaire soliciting reports about the frequency and perceived severity of specific requests for inappropriate analysis and reporting. RESULTS: Of 522 consulting biostatisticians contacted, 390 provided sufficient responses: a completion rate of 74.7%. The 4 most frequently reported inappropriate requests rated as "most severe" by at least 20% of the respondents were, in order of frequency, removing or altering some data records to better support the research hypothesis; interpreting the statistical findings on the basis of expectation, not actual results; not reporting the presence of key missing data that might bias the results; and ignoring violations of assumptions that would change results from positive to negative. These requests were reported most often by younger biostatisticians. LIMITATIONS: The survey provides information on the reported frequency of inappropriate requests but not on how such requests were handled or whether the requests reflected researchers' maleficence or inadequate knowledge about statistical and research methods. In addition, other inappropriate requests may have been made that were not prespecified in the survey. CONCLUSION: This survey suggests that researchers frequently make inappropriate requests of their biostatistical consultants regarding the analysis and reporting of their data. Understanding the reasons for these requests and how they are handled requires further study.
  6. Diet-quality scores and the risk of symptomatic gallstone disease: a prospective cohort study of male US health professionals. Wirth J, Song M, Fung TT, Joshi AD, Tabung FK, Chan AT, Weikert C, Leitzmann M, Willett WC, Giovannucci E, Wu K. Int J Epidemiol. 2018 Oct 11. doi: 10.1093/ije/dyy210. [Epub ahead of print] PMID: 30312404 Abstract OBJECTIVE: To investigate the association between three diet-quality scores corresponding to adherence to healthy dietary patterns [alternate Mediterranean (aMed), Alternate Healthy Eating Index (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH)] and the risk of symptomatic gallstone disease. METHODS: The study comprised 43 635 men of the Health Professionals Follow-up Study-an ongoing prospective cohort study of US health professionals. Participants were free of symptomatic gallstone disease and diabetes and provided dietary information every 4 years from 1986 (baseline) until 2012. The aMed, AHEI-2010 and DASH scores were generated and associated with the risk of symptomatic gallstone disease using Cox proportional hazards regression. RESULTS: During 716 904 person-years of follow-up, 2382 incident cases of symptomatic gallstone disease were identified. All three scores were inversely associated with risk of symptomatic gallstone disease after adjustment for potential confounders including age, smoking, physical activity, energy and coffee intake [hazard ratios (HRs) and 95% confidence intervals (CIs)] comparing the highest with the lowest quintiles: aMed: 0.66 (0.57-0.77), AHEI-2010: 0.64 (0.56-0.74) and DASH: 0.66 (0.58-0.76)]. Findings were similar after additional adjustment for body mass index and after inclusion of asymptomatic cases. Associations were stronger when analysis was restricted to cases who had undergone cholecystectomy. CONCLUSIONS: In this prospective cohort of male US health professionals, higher adherence to the aMed, AHEI-2010 and DASH diets was associated with lower risk of symptomatic gallstone disease. Dietary recommendations focusing on high-quality diets targeting symptomatic gallstone disease may lower the incidence of this prevalent disease. Exposure to pollen-bound pesticide mixtures induces longer-lived but less efficient honey bees. Prado A, Pioz M, Vidau C, Requier F, Jury M, Crauser D, Brunet JL, Le Conte Y, Alaux C. Sci Total Environ. 2019 Feb 10;650(Pt 1):1250-1260. doi: 10.1016/j.scitotenv.2018.09.102. Epub 2018 Sep 8. PMID: 30308813 Abstract Due to the widespread use of pesticides and their persistence in the environment, non-target organisms are chronically exposed to mixtures of toxic residues. Fungicides, herbicides and insecticides are all found at low doses in the diet of pollinators such as honey bees, but due to the lack of data on the toxicological effects of these mixtures, determining their risk is difficult to assess. We therefore developed a study combining the identification of common pollen-bound pesticide mixtures associated with poor colony development and tested their effects on bee behavior and physiology. We exposed bees to the identified pesticide mixtures during the first days of their adult life, a crucial period for physiological development. Using optic bee counters we recorded the behavior of bees throughout their lives and identified two pesticide mixtures that delay the onset of foraging and slow-down foraging activity. Furthermore, one of these mixtures hampers pollen foraging. As bee longevity is strongly influenced by the time spent foraging, bees exposed to these pesticide mixtures outlived control bees. Physiological analysis revealed that perturbations of the energetic metabolism preceded the altered behavior. In conclusion, we found that early-life exposure to low doses of pesticide mixtures can have long-term effects that translate into longer-lived but slower and less efficient bees. These surprising findings contrast with the commonly reported increase in bee mortality upon pesticide exposure, and demonstrate that exposure that may seem harmless (e.g., very low doses, pesticides not intended to kill insects) can have undesirable effects on non-target organisms. KEYWORDS: Foraging; Fungicides; Honey bee; Insecticides; Pollen; Survival Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population. Zheng JS, Lin JS, Dong HL, Zeng FF, Li D, Song Y, Chen YM. Clin Nutr. 2018 Sep 26. pii: S0261-5614(18)32456-7. doi: 10.1016/j.clnu.2018.09.018. [Epub ahead of print] PMID: 30309708 Abstract BACKGROUND & AIMS: The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population. METHODS: A total of 2671 participants, aged 40-75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA. RESULTS: After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2-4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3). CONCLUSIONS: Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings. KEYWORDS: Cohort study; Erythrocyte; Fatty acids; Prospective association; Type 2 diabetes Intake of vegetables, fruit, and fish is beneficial for Age-related Macular Degeneration. de Koning-Backus APM, Buitendijk GHS, Kiefte-de Jong JC, Colijn JM, Hofman A, Vingerling JR, Haverkort EB, Franco OH, Klaver CCW. Am J Ophthalmol. 2018 Oct 9. pii: S0002-9394(18)30578-6. doi: 10.1016/j.ajo.2018.09.036. [Epub ahead of print] PMID: 30312575 Abstract PURPOSE: What patients should eat to reduce their risk of age-related macular degeneration (AMD) is still unclear. We investigated the effect of a diet recommended by Health Councils on AMD. DESIGN: Prospective population-based cohort study. METHODS: 4202 participants from the Rotterdam Study aged 55+ years, free of AMD at baseline, were included and followed up for 9.1±5.8 years. Incident AMD was graded on fundus photographs. Dietary data were collected using a validated 170-item food frequency questionnaire, and food intakes were categorized into food patterns based on guidelines from Health Councils. Associations with incident AMD were analyzed using Cox-proportional hazards models, and adjusted for age, sex, total energy intake, smoking, body mass index, hypertension, education, and income. RESULTS: A total of 754 persons developed incident AMD. Intake of the recommended amounts of vegetables (≥200gr/day), fruit (2x/day), and fish (2x/week) was 30.6%, 54.9% and 12.5%, respectively. In particular the intake of fish (2x/week) decreased the risk of incident AMD; hazard ratio (HR) 0.76 [95% Confidence Interval (CI) 0.60-0.97]). Intake of the recommended amounts of all three food groups was only 3.7%, but adherence to this pattern showed a further reduction of the risk of incident AMD (HR 0.58 [95%CI 0.36-0.93]). Younger age, higher income, and nonsmoking were associated with this food pattern, but risk lowering effects remained significant after additional adjustment for these factors. CONCLUSION: A diet of 200 grams of vegetables/day, 2x fruit/day, and 2x fish/week is associated with a significantly reduced risk of AMD.
  7. AlPater

    Al's CR updates

    Metabolic memory of dietary restriction ameliorates DNA damage and adipocyte size in mouse visceral adipose tissue. Ishaq A, Dufour D, Cameron K, von Zglinicki T, Saretzki G. Exp Gerontol. 2018 Oct 9. pii: S0531-5565(18)30390-5. doi: 10.1016/j.exger.2018.10.008. [Epub ahead of print] PMID: 30312736 Abstract Dietary restriction (DR) is thought to exert its beneficial effects on healthspan at least partially by a senolytic and senostatic action, i.e. by reducing frequencies of cells with markers of DNA damage and senescence in multiple tissues. Due to its importance in metabolic and inflammation regulation, fat is a prime tissue for health span determination as well as a prime target for DR. We aimed to determine here whether the beneficial effects of DR would be retained over a subsequent period of ad libitum (AL) feeding. Male mice were kept under either 40% DR or AL feeding regimes from 3 to 12 months of age and then either switched back to the opposite feeding regimen or kept in the same state for another 3 months. Visceral adipose tissue from 4 to 5 mice per group for all conditions was analysed for markers of senescence (adipocyte size, γH2A.X, p16, p21) and inflammation (e.g. IL-6, TNFα, IL-1β) using immuno-staining or qPCR. Macrophages were detected by immunohistochemistry. We found that both 9 and 12 months DR (long term) as well as 3 month (short term, mid-life onset) DR reduced the number of cells harbouring DNA damage and adipocyte size (area and perimeter) in visceral adipocytes with similar efficiency. Importantly, beneficial health markers induced by DR such as small adipocyte size and low DNA damage were maintained for at least 3 month after termination of DR, demonstrating that the previously identified 'metabolic memory' of the DR state in male mice extends to senescence markers in visceral fat. KEYWORDS: Adipose tissue; Ageing; DNA damage; Dietary restriction; Metabolic; Mice; Senescence New Study Shows that Whey Protein is the Best Way for Older Adults to Rebuild Muscle PR Newswire (press release) https://www.prnewswire.com/news-releases/new-study-shows-that-whey-protein-is-the-best-way-for-older-adults-to-rebuild-muscle-300727150.html >>>>>>>>>>>>>>>>>>>>>> A randomized controlled trial of the impact of protein supplementation on leg lean mass and integrated muscle protein synthesis during inactivity and energy restriction in older persons Sara Y Oikawa Chris McGlory Lisa K D'Souza Adrienne K Morgan Nelson I Saddler Steven K Baker Gianni Parise Stuart M Phillips The American Journal of Clinical Nutrition, nqy193, https://doi.org/10.1093/ajcn/nqy193 Published: 04 October 2018 https://sci-hub.tw/10.1093/ajcn/nqy193 ABSTRACT Background In older persons, muscle loss is accelerated during physical inactivity and hypoenergetic states, both of which are features of hospitalization. Protein supplementation may represent a strategy to offset the loss of muscle during inactivity, and enhance recovery on resumption of activity. Objective We aimed to determine if protein supplementation, with proteins of substantially different quality, would alleviate the loss of lean mass by augmenting muscle protein synthesis (MPS) while inactive during a hypoenergetic state. Design Participants (16 men, mean ± SD age: 69 ± 3 y; 15 women, mean ± SD age: 68 ± 4 y) consumed a diet containing 1.6 g protein · kg–1 · d–1, with 55% ± 9% of protein from foods and 45% ± 9% from supplements, namely, whey protein (WP) or collagen peptides (CP): 30 g each, consumed 2 times/d. Participants were in energy balance (EB) for 1 wk, then began a period of energy restriction (ER; –500 kcal/d) for 1 wk, followed by ER with step reduction (ER + SR; <750 steps/d) for 2 wk, before a return to habitual activity in recovery (RC) for 1 wk. Results There were significant reductions in leg lean mass (LLM) from EB to ER, and from ER to ER + SR in both groups (P < 0.001) with no differences between WP and CP or when comparing the change from phase to phase. During RC, LLM increased from ER + SR, but in the WP group only. Rates of integrated muscle protein synthesis decreased during ER and ER + SR in both groups (P < 0.01), but increased during RC only in the WP group (P = 0.05). Conclusions Protein supplementation did not confer a benefit in protecting LLM, but only supplemental WP augmented LLM and muscle protein synthesis during recovery from inactivity and a hypoenergetic state. This trial was registered at http://www.clinicaltrials.gov as NCT03285737. Keyword: muscle protein synthesis, older adults, whey protein, collagen peptides, step reduction
  8. Fasting enhances extinction retention and prevents the return of fear in humans. Shi L, Deng J, Chen S, Que J, Sun Y, Wang Z, Guo X, Han Y, Zhou Y, Zhang X, Xie W, Lin X, Shi J, Lu L. Transl Psychiatry. 2018 Oct 9;8(1):214. doi: 10.1038/s41398-018-0260-1. PMID: 30301955 https://www.nature.com/articles/s41398-018-0260-1 Abstract Fear is prone to return following extinction that is the basis of exposure therapy for fear-related disorders. Manipulations that enhance the extinction process can be beneficial for treatment. Animal studies have shown that fasting or caloric restriction can enhance extinction and inhibit the return of fear. The present study examined the effects of fasting on fear acquisition, extinction, and the return of fear in humans. One hundred and twenty-five male participants were randomized into a fasting group and food group and exposed to a Pavlovian fear conditioning paradigm. Changes in plasma cortisol and ghrelin levels were examined using enzyme-linked immunosorbent assays. One-night fasting had no effect on fear acquisition but enhanced fear extinction retention and prevented the return of fear, and this effect persisted for at least 6 months. This procedure was also effective for remote fear memory. Plasma ghrelin levels were elevated after fasting and had a negative relationship with the fear response in spontaneous recovery test. However, overnight fasting did not affect cortisol levels. These findings indicate that fasting enhances extinction retention and prevents the return of fear, without influencing fear memory formation. We propose that this novel procedure may open new avenues for promoting extinction-based therapies for fear-related disorders. Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans? Madeo F, Bauer MA, Carmona-Gutierrez D, Kroemer G. Autophagy. 2018 Oct 11:1-4. doi: 10.1080/15548627.2018.1530929. [Epub ahead of print] PMID: 30306826 https://sci-hub.tw/10.1080/15548627.2018.1530929 Abstract Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested. Recent epidemiological data support this notion, showing that an increased uptake of this polyamine with spermidine-rich food diminishes overall mortality associated with cardiovascular diseases and cancer. Here, we discuss nutritional and other possible routes to counteract the age-mediated decline of spermidine levels. KEYWORDS: Autophagy; cancer; cardiovascular diseases; health span extension; longevity Acute Effects of Substitution, and Addition, of Carbohydrates and Fat to Protein on Gastric Emptying, Blood Glucose, Gut Hormones, Appetite, and Energy Intake. Giezenaar C, Lange K, Hausken T, Jones KL, Horowitz M, Chapman I, Soenen S. Nutrients. 2018 Oct 7;10(10). pii: E1451. doi: 10.3390/nu10101451. PMID: 30301241 https://www.mdpi.com/2072-6643/10/10/1451/htm Abstract Whey protein, when ingested on its own, load-dependently slows gastric emptying and stimulates gut hormone concentrations in healthy young men. The aim of this study was to determine the effects of substitution, and addition, of carbohydrate (dextrose) and fat (olive oil) to whey protein. In randomized, double-blind order, 13 healthy young men (age: 23 ± 1 years, body mass index: 24 ± 1 kg/m²) ingested a control drink (450 mL; ~2 kcal/'control') or iso-volumetric drinks containing protein/carbohydrate/fat: (i) 14 g/28 g/12.4 g (280 kcal/'M280'), (ii) 70 g/28 g/12.4 g (504kcal/'M504'), and (iii) 70 g/0 g/0 g (280 kcal/'P280'), on 4 separate study days. Gastric emptying (n = 11, 3D-ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) concentrations (0⁻180 min), appetite (visual analogue scales), and ad-libitum buffet-meal energy intake (180⁻210 min) were determined. Substitution of protein with carbohydrate and fat was associated with faster gastric emptying (lower 50% emptying time (T50)), reduced suppression of ghrelin, and stimulation of GLP-1 (all P < 0.001); while the addition of carbohydrate and fat to protein did not affect gastric emptying or gut hormone responses significantly. Total energy intake (i.e., drink plus meal) was greater after all caloric drinks than control (P < 0.001). In conclusion, substitution of whey protein with dextrose and olive oil accelerated gastric emptying. Higher protein content of a mixed macronutrient drink increased gut hormone and insulin responses. KEYWORDS: appetite; blood glucose; gastric emptying; gut hormones; whey protein Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. Imamura F, Fretts A, Marklund M, Ardisson Korat AV, Yang WS, Lankinen M, Qureshi W, Helmer C, Chen TA, Wong K, Bassett JK, Murphy R, Tintle N, Yu CI, Brouwer IA, Chien KL, Frazier-Wood AC, Del Gobbo LC, Djoussé L, Geleijnse JM, Giles GG, de Goede J, Gudnason V, Harris WS, Hodge A, Hu F; InterAct Consortium, Koulman A, Laakso M, Lind L, Lin HJ, McKnight B, Rajaobelina K, Risérus U, Robinson JG, Samieri C, Siscovick DS, Soedamah-Muthu SS, Sotoodehnia N, Sun Q, Tsai MY, Uusitupa M, Wagenknecht LE, Wareham NJ, Wu JH, Micha R, Forouhi NG, Lemaitre RN, Mozaffarian D; Fatty Acids and Outcomes Research Consortium (FORCE). PLoS Med. 2018 Oct 10;15(10):e1002670. doi: 10.1371/journal.pmed.1002670. eCollection 2018 Oct. PMID: 30303968 Abstract BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. CONCLUSIONS: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D. The Effects of Dietary Flaxseed on Cardiac Arrhythmias and Claudication in Patients with Peripheral Arterial Disease. Rodriguez Leyva D, Rodriguez-Portelles A, Weighell W, Guzman R, Maddaford TG, Pierce GN. Can J Physiol Pharmacol. 2018 Oct 11. doi: 10.1139/cjpp-2018-0280. [Epub ahead of print] PMID: 30308127 Abstract Patients with peripheral artery disease (PAD) are at increased risk for cardiovascular events and higher susceptibility for cardiac arrhythmias may be involved. The objectives of this double blinded, randomized controlled FLAX-PAD trial were to determine whether daily consumption of a diet supplemented with 30g of milled flaxseed (or placebo) over one year by PAD patients has effects on the prevalence of cardiac arrhythmias and exercise capacity. Cardiac arrhythmias were assessed on a cardiac stress test and at rest. At baseline, the PAD patients had a high incidence of cardiac arrhythmias (48% in the flaxseed group and 32% in the placebo group). After 1 year, the presence of cardiac arrhythmias in the flaxseed group decreased by 2% and increased by 12% in the placebo group (P>0.05). Electrocardiographic variables (P, PR, QRS, QT, QTc) did not change in either group during the trial. Patients from both groups improved initial and absolute claudication distances but the intergroup difference was also not statistically significant. In summary, the prevalence of cardiac arrhythmias and physical capacity trended in a positive direction for patients ingesting flaxseed but either a larger sample size or a longer intervention with flaxseed may be required to show statistically significant differences.
  9. AlPater

    Al's CR updates

    Do the Effects of Resveratrol on Thermogenic and Oxidative Capacities in IBAT and Skeletal Muscle Depend on Feeding Conditions? Milton-Laskibar I, Aguirre L, Etxeberria U, Milagro FI, Martínez JA, Portillo MP. Nutrients. 2018 Oct 6;10(10). pii: E1446. doi: 10.3390/nu10101446. PMID: 30301195 https://www.mdpi.com/2072-6643/10/10/1446/htm Abstract The aim of this study was to compare the effects of mild energy restriction and resveratrol on thermogenic and oxidative capacity in interscapular brown adipose tissue (IBAT) and in skeletal muscle. Rats were fed a high-fat high-sucrose diet for six weeks, and divided into four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy-restricted group and an energy-restricted group treated with resveratrol. Weights of IBAT, gastrocnemius muscle and fat depots were measured. Activities of carnitine palmitoyltransferase (CPT) and citrate synthase (CS), protein levels of sirtuin (SIRT1 and 3), uncoupling proteins (UCP1 and 3), glucose transporter (GLUT4), mitochondrial transcription factor (TFAM), nuclear respiratory factor (NRF1), peroxisome proliferator-activated receptor (PPARα) and AMP activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC1α) activation were measured. No changes in IBAT and gastrocnemius weights were found. Energy-restriction, but not resveratrol, decreased the weights of adipose depots. In IBAT, resveratrol enhanced thermogenesis activating the SIRT1/PGC1α/PPARα axis. Resveratrol also induced fatty acid oxidation and glucose uptake. These effects were similar when resveratrol was combined with energy restriction. In the case of gastrocnemius muscle, the effects were not as clear as in the case of IBAT. In this tissue, resveratrol increased oxidative capacity. The combination of resveratrol and energy restriction seemingly did not improve the effects induced by the polyphenol alone. KEYWORDS: energy restriction; high-fat high-sucrose diet; rat; resveratrol; thermogenesis
  10. Effect of Low Dose Docosahexaenoic Acid-Rich Fish Oil on Plasma Lipids and Lipoproteins in Pre-Menopausal Women: A Dose⁻Response Randomized Placebo-Controlled Trial. Sparkes C, Gibson R, Sinclair A, Else PL, Meyer BJ. Nutrients. 2018 Oct 8;10(10). pii: E1460. doi: 10.3390/nu10101460. PMID: 30297663 https://www.mdpi.com/2072-6643/10/10/1460/htm Abstract Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation has been shown to improve plasma lipid profiles in men and post-menopausal women, however, data for pre-menopausal women are lacking. The benefits of intakes less than 1 g/day have not been well studied, and dose⁻response data is limited. The aim of this study was to determine the effect of low doses of docosahexaenoic acid (DHA)-rich tuna oil on plasma triglyceride (TG) lowering in pre-menopausal women, and investigate if low dose DHA-rich tuna oil supplementation would increase the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle sizes. A randomized, double-blind, placebo-controlled trial was conducted, in which 53 healthy pre-menopausal women with mildly elevated plasma TG levels consumed 0, 0.35, 0.7, or 1 g/day n-3 LCPUFA as HiDHA™ tuna oil or placebo (Sunola oil) capsules for 8 weeks. Supplementation with 1 g/day n-3 LCPUFA, but not lower doses, reduced plasma TG by 23% in pre-menopausal women. This was reflected in a dose-dependent reduction in very-low-density lipoprotein (VLDL)-TG (R² = 0.20, p = 0.003). A weak dose-dependent shift in HDL (but not LDL) particle size was identified (R² = 0.05, p = 0.04). The results of this study indicate that DHA-rich n-3 LCPUFA supplementation at a dose of 1 g/day is an effective TG-lowering agent and increases HDL particle size in pre-menopausal women. KEYWORDS: DHA; lipoproteins; plasma lipids; premenopausal women
  11. Intermittent administration of a leucine-deprived diet is able to intervene in type 2 diabetes in db/db mice. Wei S, Zhao J, Wang S, Huang M, Wang Y, Chen Y. Heliyon. 2018 Sep 27;4(9):e00830. doi: 10.1016/j.heliyon.2018.e00830. eCollection 2018 Sep. PMID: 30294696 Abstract Continuous deficiency of leucine, a member of branched chain amino acids, is able to reduce obesity and improve insulin sensitivity in mice. Intermittent fasting has been shown to be effective in intervention of metabolic disorders including diabetes. However, it is unknown whether intermittent leucine deprivation can intervene in type 2 diabetes progression. We administered leucine-deprived food every other day in db/db mice, a type 2 diabetes model, for a total of eight weeks to investigate the interventional effect of intermittent leucine deprivation. Intermittent leucine deprivation significantly reduces hyperglycemia in db/db mice independent of body weight change, together with improvement in glucose tolerance and insulin sensitivity. The total area of pancreatic islets and β cell number are increased by intermittent leucine deprivation, accompanied by elevated proliferation of β cells. The expression level of Ngn3, a β cell progenitor marker, is also increased by leucine-deleted diet. However, leucine deficiency engenders an increase in fat mass and a decrease in lean mass. Lipid accumulation in the liver is elevated and liver function is compromised by leucine deprivation. In addition, leucine deficiency alters the composition of gut microbiota. Leucine deprivation increases the genera of Bacteroides, Alloprevotella, Rikenellaceae while reduces Lachnospiraceae and these changes are correlated with fasting blood glucose levels of the mice. Collectively, our data demonstrated that intermittent leucine deprivation can intervene in the progression of type 2 diabetes in db/db mice. However, leucine deficiency reduces lean mass and aggravates hepatic steatosis in the mouse. Human Umbilical Cord Blood Plasma Alleviates Age-related Olfactory Dysfunction by Attenuating Peripheral TNF-α expression. Lee BC, Kang I, Lee SE, Lee JY, Shin N, Kim JJ, Choi SW, Kang KS. BMB Rep. 2018 Oct 8. pii: 4223. [Epub ahead of print] PMID: 30293545 pdf available from http://submit.bmbreports.org/Search/View.html?tmp_tr_num=4223 Abstract Social requirements are needed for living in an aging society and individual longevity. Among them, improved health and medical cares, appropriate for an aging society are strongly demanded. Human cord blood-derived plasma (hUCP) has recently emerged for its unique anti-aging effects. In this study, we investigated brain rejuvenation, particularly olfactory function, that could be achieved by a systemic administration of young blood and its underlying mechanisms. Older than 24-month-old mice were used as an aged group and administered with intravenous injection of hUCP repetitively, eight times. Anti-aging effect of hUCP on olfactory function was evaluated by buried food finding test. To investigate the mode of action of hUCP, brain, serum and spleen of mice were collected for further ex vivo analyses. Systemic injection of hUCP improved aging-associated olfactory deficits, reducing time for finding food. In the brain, although an infiltration of activated microglia and its expression of cathepsin S remarkably decreased, significant changes of proinflammatory factors were not detected. Conversely, peripheral immune balance distinctly switched from predominance of Type 1 helper T (Th1) cells to alternative regulatory T cells (Tregs). These findings indicate that systemic administration of hUCP attenuates age-related neuroinflammation and subsequent olfactory dysfunction by modulating peripheral immune balance toward Treg cells, suggesting another therapeutic function and mechanism of hUCP administration.
  12. Commonly?: https://www.ncbi.nlm.nih.gov/pubmed/2294762 : "These symptoms did not result in a decreased ability to perform usual daily activities" versus getting the flu. How many get the flu: https://www.webmd.com/cold-and-flu/flu-statistics .
  13. Influence of corticosterone on growth, home-cage activity, wheel running, and aerobic capacity in house mice selectively bred for high voluntary wheel-running behavior. Singleton JM, Garland T Jr. Physiol Behav. 2018 Oct 4. pii: S0031-9384(18)30459-1. doi: 10.1016/j.physbeh.2018.10.001. [Epub ahead of print] PMID: 30292826 https://sci-hub.tw/https://linkinghub.elsevier.com/retrieve/pii/S0031938418304591 Abstract Glucocorticoids, a class of metabolic hormones, impact a wide range of traits (e.g., behavior, skeletal growth, muscle maintenance, glucose metabolism), and variation in concentrations of circulating glucocorticoids (such as corticosterone), at the level of natural individual variation, in relation to endocrine disorders, or from exogenous supplementation, have manifold effects. Changes in circulating corticosterone concentrations can also impact multiple aspects of locomotor behavior, including both motivation and physical ability for exercise. To examine further the role of corticosterone in locomotor behavior and associated traits, we utilized laboratory house mice from a long-term experiment that selectively breeds for high levels of voluntary exercise. As compared with four non-selected control (C) lines, mice from the four replicate High Runner (HR) lines have ~2-fold higher baseline circulating corticosterone concentrations as well as ~3-fold higher voluntary wheel running on a daily basis, higher home-cage activity when deprived of wheels, higher maximal aerobic capacity, and smaller body size; potentially, all of these differences could be modulated by circulating corticosterone. We administered 50 μg/ml corticosterone-21-hemisuccinate in the drinking water of both HR and C male mice from weaning through ~8 weeks of age. As compared with mice from C lines, HR mice had higher endogenous corticosterone levels; higher daily wheel-running distance, duration, and speed; higher maximal oxygen consumption during forced exercise (VO2max); spent more time in the closed arms of an elevated plus maze; and had larger reproductive fat pads. For both HR and C mice, corticosterone treatment strongly suppressed endogenous circulating corticosterone levels, decreased growth rate and adult body mass, increased food and water consumption (both adjusted for body mass), increased entries into closed arms of an elevated plus maze, decreased home-cage activity (total and average intensity), decreased wheel-running distance and maximum speed, and decreased VO2max. At the suborganismal level, corticosterone treatment decreased relative adrenal, liver, and triceps surae muscle mass, as well as tail length, but increased both subdermal and reproductive fat pad masses, as well as hematocrit. Overall, the responses of both HR and C mice to corticosterone supplementation were "negative" from a health perspective. These results have significant implications for understanding both the evolution of baseline corticosterone levels and stress-related effects on activity levels. They also suggest that patients experiencing extended periods of glucocorticoid treatment might benefit from attempts to increase their physical activity as an adjuvant. KEYWORDS: Artificial selection; Body composition; Exercise; Food consumption; Growth; Locomotion Population-based studies of relationships between dietary acidity load, insulin resistance and incident diabetes in Danes. Gæde J, Nielsen T, Madsen ML, Toft U, Jørgensen T, Overvad K, Tjønneland A, Hansen T, Allin KH, Pedersen O. Nutr J. 2018 Oct 6;17(1):91. doi: 10.1186/s12937-018-0395-1. PMID: 30292239 https://nutritionj.biomedcentral.com/track/pdf/10.1186/s12937-018-0395-1 Abstract BACKGROUND: It has been suggested that the acidity of the diet may be related to increased risk of type 2 diabetes. To investigate this hypothesis, we tested if the acidity of the diet, measured as the Potential Renal Acid Load (PRAL) score, was associated with incident diabetes and diabetes-related intermediary traits. METHODS: A total of 54,651 individuals from the Danish Diet, Cancer and Health (DCH) cohort were included in the prospective cox regression analyses of incident diabetes over a 15 years follow-up period. Moreover, 5724 Danish individuals with baseline data from the Inter99 cohort were included in the cross sectional, multivariate and logistic regression analyses of measures of insulin sensitivity, insulin release and glucose tolerance status derived from an oral glucose tolerance test (OGTT). RESULTS: In the DCH cohort a trend analysis showed that quintiles of PRAL score were, after multifactorial adjustment, associated with a higher incidence of diabetes (ptrend = 6 × 10- 7). HR for incident diabetes was 1.24 (1.14; 1.35) (p = 7 × 10- 7) between first and fifth PRAL score quintile. In Inter99 higher PRAL score associated with insulin resistance as estimated by lower BIGTT-Si (an OGTT-derived index of insulin sensitivity) (p = 4 × 10- 7) and Matsuda index of insulin sensitivity (p = 2 × 10- 5) as well as higher HOMA-IR (p = 0.001). No association was observed for measures of insulin release, but higher PRAL score was associated with lower OGTT-based disposition index. CONCLUSIONS: A high dietary acidity load is associated with a higher risk of diabetes among middle-aged Danes. Although adjustment for BMI attenuated the effect sizes the association remained significant. The increased risk of diabetes may be related to our finding that a high dietary acidity load associates with impaired insulin sensitivity. KEYWORDS: Dietary acid load; Disposition index; Glucose; Insulin resistance; PRAL; Type 2 diabetes
  14. Nutritional epidemiology and cancer: A Tale of Two Cities. Giovannucci E. Cancer Causes Control. 2018 Oct 5. doi: 10.1007/s10552-018-1088-y. [Epub ahead of print] PMID: 30291578 https://sci-hub.tw/10.1007/s10552-018-1088-y Abstract Recently, Ioannidis questioned whether nutritional epidemiology could be reconciled with good scientific principles, and suggested that the field needs radical reform. One of the reforms he advocated was more randomized trials; though what diet would be tested and how it would be measured were unspecified, how adherence would be monitored was unclear or unimportant, and the length of time vaguely stated as "lifelong". The other reform was reanalysis of shared data, which actually already exists in a large number of cohort consortia of individual pooled data. The 2018 report analysis of diet and cancer from the World Cancer Fund/American Institute of Cancer Research presents a sharply different picture of our knowledge of nutrition and cancer, which has evolved immensely in the past 3 decades. Based on current knowledge, factors related to energy balance, encompassed by body mass anthropometric measures might account for about 10-15% of the U.S. cancer burden. This 10-15% encompasses physical activity and obesogenic effects of diet. About 5% may be attributable to alcohol, and another 5% to specific dietary factors combined (e.g., red and processed meat, whole grains, fiber, calcium, fruits, and vegetables). Surrogates such as attained height and age at menarche are influenced by nutrition and are consistent risk factors for cancer, supporting the importance of early nutrition. Recent data suggest that early life dietary patterns, which may be modifiable, may be important. Though important questions remain, our understanding of nutrition and cancer over the life course is coherent and has been informed by nutritional epidemiology and other data. KEYWORDS: Cancer; Diet; Epidemiology; Nutritional epidemiology
  15. AlPater

    Al's CR updates

    Insulin, carbohydrate restriction, metabolic syndrome and cancer. Fine EJ, Feinman RD. Expert Rev Endocrinol Metab. 2015 Jan;10(1):15-24. doi: 10.1586/17446651.2014.960392. Epub 2014 Sep 22. PMID: 30289045 https://sci-hub.tw/10.1586/17446651.2014.960392 Abstract We propose that dietary carbohydrate restriction, particularly ketogenic diets, may provide benefit as a therapeutic or preventive strategy in cancer, alone or as an adjunct to pharmacology. The argument derives from several points of evidence: There is a close association between cancer and both diabetes and obesity. Extensive evidence shows that low carbohydrate diets are the most effective dietary treatment of Type 2 diabetes and dietary adjunct in Type 1. Such diets also target all the markers of metabolic syndrome. Finally, de facto reduction in carbohydrate likely contributes to total dietary restriction, which is effective in the prevention and treatment of cancer. The idea is consistent with recent interest in treating cancer with drugs that target diabetes. To move forward, we must understand obesity and diabetes as response to a hyperglycemic state rather than simply a cause of downstream effects. KEYWORDS: IGF; caloric restriction; cancer; insulin; ketogenic diet; low carbohydrate diet; metabolic syndrome