Jump to content


  • Content Count

  • Joined

  • Last visited

About AlPater

  • Birthday 06/09/1947

Profile Information

  • Gender

Recent Profile Visitors

1,120 profile views
  1. Sex Differences In Postprandal Responses To Different Dairy Products On Lipoprotein Subclasses: A Randomized Controlled Cross-Over Trial. Hansson P, Holven KB, Øyri LKL, Brekke HK, Gjevestad GO, Thoresen M, Ulven SM. Br J Nutr. 2019 Jun 18:1-25. doi: 10.1017/S0007114519001429. [Epub ahead of print] PMID: 31208475 Abstract Men have earlier first time event of coronary heart disease, and higher postprandial triglyceride response, compared to women. The aim of this exploratory sub-study was to investigate if intake of meals with the same amount of fat from different dairy products affects postprandial lipoprotein subclasses differently in healthy women and men. Thirty-three women and 14 men were recruited to a randomized controlled cross-over study with four dairy meals consisting of butter, cheese, whipped cream or sour cream, corresponding to 45 grams of fat (approximately 60 energy percent). Blood samples were taken at 0, 2, 4 and 6 hours postprandially. Lipoprotein subclasses were measured using nuclear magnetic resonance, and analyzed using a linear mixed model. Sex had a significant impact on the response in M-VLDL (P=0.04), S-LDL (P=0.05), XL-HDL (P=0.009), and L-HDL (P=0.001) particle concentration (P), with women having an overall smaller increase in M-VLDL-P, a larger decrease in S-LDL-P, and a larger increase in XL-, and L-HDL-P compared to men, independent of meal. Men showed a decrease in XS-VLDL-P compared to women after intake of sour cream (P&lt;0.01). In men only, XS-VLDL-P decreased after intake of sour cream compared to all other meals (vs. butter: P=0.001; vs. cheese: P&lt;0.04; vs. whipped cream: P=0.006). Meals with the same amount of fat from different dairy products induce different postprandial effects on lipoprotein subclass concentrations in men and women. KEYWORDS: CHD Coronary heart disease CRP C-reactive protein CVD Cardiovascular disease E% Energy percent HDL-C High-density lipoprotein-cholesterol iAUC Incremental area under the curve IDL Intermediate-density lipoprotein IS Ischemic stroke L Large LDL-C Low-density lipoprotein-cholesterol LPL Lipoprotein lipase M Medium MFGM Milk fat globule membrane MI Myocardial infarction P Particle concentration S Small TC Total cholesterol TG Triglyceride TRL Triglyceride-rich lipoprotein XL Very large XS Very small XXL Extremely large; HDL; LDL; VLDL; butter; cheese; cream; dairy matrix; lipoprotein subclasses; postprandial; sex differences; sour cream Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults. Shi L, Brunius C, Bergdahl IA, Johansson I, Rolandsson O, Donat Vargas C, Kiviranta H, Hanhineva K, Åkesson A, Landberg R. J Nutr. 2019 Jun 18. pii: nxz068. doi: 10.1093/jn/nxz068. [Epub ahead of print] PMID: 31209490 Abstract BACKGROUND: There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish. OBJECTIVE: The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults. METHODS: In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression. RESULTS: We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P < 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake. CONCLUSIONS: Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence. EYWORDS: O2PLS modeling; fish biomarkers; metabolomics; nested case-control study; persistent organic pollutants; type 2 diabetes
  2. Effects of the DASH Diet and Sodium Intake on Bloating: Results From the DASH-Sodium Trial. Peng AW, Juraschek SP, Appel LJ, Miller ER 3rd, Mueller NT. Am J Gastroenterol. 2019 Jun 17. doi: 10.14309/ajg.0000000000000283. [Epub ahead of print] PMID: 31206400 Abstract INTRODUCTION: Bloating is one of the most common gastrointestinal complaints. Evidence has linked fiber and sodium to bloating; however, randomized trials examining these diet components are lacking. Here, we used a randomized trial to examine the effects of the high-fiber DASH diet and dietary sodium intake on abdominal bloating. We hypothesized that both the high-fiber DASH diet and higher sodium intake would increase bloating. METHODS: The DASH-Sodium trial (1998-1999) randomized healthy adults to a high-fiber (32 g/d) DASH or low-fiber (11 g/d) Western diet (control). On their assigned diet, participants ate 3 sodium levels (50, 100, and 150 mmol/d at 2100 kcal) in 30-day periods in random order, with 5-day breaks between each period. The participants reported the presence of bloating at baseline and after each feeding period. Statistical analyses included log-binomial models to evaluate the risk of bloating. RESULTS: Of 412 participants (mean age 48 years; 57% women; 57% black), 36.7% reported bloating at baseline. Regardless of the diet, high sodium intake increased the risk of bloating (risk ratio = 1.27; 95% confidence interval: 1.06-1.52; P = 0.01). The high-fiber DASH diet also increased the risk of bloating over all sodium levels (risk ratio = 1.41; 95% confidence interval: 1.22-1.64; P < 0.001). The effect of high-fiber DASH on bloating was greater in men than in women (P for interaction = 0.001). DISCUSSION: Higher dietary sodium increased bloating, as did the high-fiber DASH diet. Although healthful high-fiber diets may increase bloating, these effects may be partially mitigated by decreasing dietary sodium intake. Future research is needed to explore mechanisms by which sodium intake and diet can influence bloating.
  3. Dietary vinegar prevents kidney stone recurrence via epigenetic regulations. Zhu W, Liu Y, Lan Y, Li X, Luo L, Duan X, Lei M, Liu G, Yang Z, Mai X, Sun Y, Wang L, Lu S, Ou L, Wu W, Mai Z, Zhong D, Cai C, Zhao Z, Zhong W, Liu Y, Sun Y, Zeng G. EBioMedicine. 2019 Jun 12. pii: S2352-3964(19)30379-2. doi: 10.1016/j.ebiom.2019.06.004. [Epub ahead of print] PMID: 31202812 https://www.ebiomedicine.com/article/S2352-3964(19)30379-2/pdf Abstract BACKGROUND: Epidemiological evidence of over 9000 people suggests that daily intake of vinegar whose principal bioactive component is acetic acid is associated with a reduced risk of nephrolithiasis. The underlying mechanism, however, remains largely unknown. METHODS: We examined the in vitro and in vivo anti-nephrolithiasis effects of vinegar and acetate. A randomized study was performed to confirm the effects of vinegar in humans. FINDINGS: We found individuals with daily consumption of vinegar compared to those without have a higher citrate and a lower calcium excretion in urine, two critical molecules for calcium oxalate (CaOx) kidney stone in humans. We observed that oral administration of vinegar or 5% acetate increased citrate and reduced calcium in urinary excretion, and finally suppressed renal CaOx crystal formation in a rat model. Mechanism dissection suggested that acetate enhanced acetylation of Histone H3 in renal tubular cells and promoted expression of microRNAs-130a-3p, -148b-3p and -374b-5p by increasing H3K9, H3K27 acetylation at their promoter regions. These miRNAs can suppress the expression of Nadc1 and Cldn14, thus enhancing urinary citrate excretion and reducing urinary calcium excretion. Significantly these mechanistic findings were confirmed in human kidney tissues, suggesting similar mechanistic relationships exist in humans. Results from a pilot clinical study indicated that daily intake of vinegar reduced stone recurrence, increased citrate and reduced calcium in urinary excretion in CaOx stone formers without adverse side effects. INTERPRETATION: Vinegar prevents renal CaOx crystal formation through influencing urinary citrate and calcium excretion via epigenetic regulations. Vinegar consumption is a promising strategy to prevent CaOx nephrolithiasis occurrence and recurrence. KEYWORDS: Acetate; Calcium; Citrate; Epigenetic regulation; Nephrolithiasis; Vinegar; microRNA
  4. Depressive Disorders and Religious Engagement in Very Old People.Strinnholm S, Gustafson Y, Niklasson J.Gerontol Geriatr Med. 2019 May 10;5:2333721419846576. doi: 10.1177/2333721419846576. eCollection 2019 Jan-Dec.PMID: 31192277AbstractObjective: To examine associations between religious engagement and depressive disorders in very old people. Method: This cross-sectional study uses data from the Umeå 85+/Gerontological Regional Database (GERDA) study. Every other 85-year-old, every 90-year-old, and everyone more than 95 years from eight municipalities in northern Sweden and Finland were invited: 1,014 persons accepted participation. Data were gathered using questionnaires and assessment scales during structured home visits. Results: The prevalence of depressive disorders was 35.8%. In a logistic regression model, several factors were adjusted for, such as demographic variables including social factors, diseases, and cognitive and physical functional level. A high level of self-reported religious engagement was independently associated with not having depressive disorders (odds ratio [OR] = 0.58, confidence interval [CI] = [0.38, 0.89]). After stratifying by gender, religious engagement was only significant for women (OR = 0.49, CI = [0.29, 0.82]). Discussion: There is an association between a high level of religious engagement and being free from diagnosis of depressive disorders among very old women.KEYWORDS:80 and above; aged; depression; religion; salutogenesisUp-regulation of FOXO1 and reduced inflammation by β-hydroxybutyric acid are essential diet restriction benefits against liver injury.Miyauchi T, Uchida Y, Kadono K, Hirao H, Kawasoe J, Watanabe T, Ueda S, Okajima H, Terajima H, Uemoto S.Proc Natl Acad Sci U S A. 2019 Jun 13. pii: 201820282. doi: 10.1073/pnas.1820282116. [Epub ahead of print]PMID: 31196960AbstractLiver ischemia and reperfusion injury (IRI) is a major challenge in liver surgery. Diet restriction reduces liver damage by increasing stress resistance; however, the underlying molecular mechanisms remain unclear. We investigated the preventive effect of 12-h fasting on mouse liver IRI. Partial warm hepatic IRI model in wild-type male C57BL/6 mice was used. The control ischemia and reperfusion (IR) group of mice was given food and water ad libitum, while the fasting IR group was given water but not food for 12 h before ischemic insult. In 12-h fasting mice, serum liver-derived enzyme level and tissue damages due to IR were strongly suppressed. Serum β-hydroxybutyric acid (BHB) was significantly raised before ischemia and during reperfusion. Up-regulated BHB induced an increment in the expression of FOXO1 transcription factor by raising the level of acetylated histone. Antioxidative enzyme heme oxigenase 1 (HO-1), a target gene of FOXO1, then increased. Autophagy activity was also enhanced. Serum high-mobility group box 1 was remarkably lowered by the 12-h fasting, and activation of NF-κB and NLRP3 inflammasome was suppressed. Consequently, inflammatory cytokine production and liver injury were reduced. Exogenous BHB administration or histone deacetylase inhibitor administration into the control fed mice ameliorated liver IRI, while FOXO1 inhibitor administration to the 12-h fasting group exacerbated liver IRI. The 12-h fasting exerted beneficial effects on the prevention of liver IRI by increasing BHB, thus up-regulating FOXO1 and HO-1, and by reducing the inflammatory responses and apoptotic cell death via the down-regulation of NF-κB and NLRP3 inflammasome.KEYWORDS:FOXO1; fasting; ischemia and reperfusion injury; β-hydroxybutyric acidDietary Glycemic Index and Load and the Risk of Type 2 Diabetes: A Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies.Livesey G, Taylor R, Livesey HF, Buyken AE, Jenkins DJA, Augustin LSA, Sievenpiper JL, Barclay AW, Liu S, Wolever TMS, Willett WC, Brighenti F, Salas-Salvadó J, Björck I, Rizkalla SW, Riccardi G, La Vecchia C, Ceriello A, Trichopoulou A, Poli A, Astrup A, Kendall CWC, Ha MA, Baer-Sinnott S, Brand-Miller JC.Nutrients. 2019 Jun 5;11(6). pii: E1280. doi: 10.3390/nu11061280. Review.PMID: 31195724AbstractPublished meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dose-response meta-analysis(DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relationswould support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit>1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). Thecombined T2D-GI RR was 1.27 (1.15-1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that forthe T2D-GL RR was 1.26 (1.15-1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet.The corresponding global DRM using restricted cubic splines were 1.87 (1.56-2.25) (p < 0.001, n =10) and 1.89 (1.66-2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GLwere robustly associated with incident T2D. Together with mechanistic and other data, thissupports that consideration should be given to these dietary risk factors in nutrition advice.Concerning the public health relevance at the global level, our evidence indicates that GI and GLare substantial food markers predicting the development of T2D worldwide, for persons ofEuropean ancestry and of East Asian ancestry.KEYWORDS:alcohol; cohort studies; dietary fiber; epidemiology; glycemic index; glycemic load; meta-analysis; protein; type 2 diabetesAspirin for Primary Prevention of Cardiovascular Events.Abdelaziz HK, Saad M, Pothineni NVK, Megaly M, Potluri R, Saleh M, Kon DLC, Roberts DH, Bhatt DL, Aronow HD, Abbott JD, Mehta JL.J Am Coll Cardiol. 2019 Jun 18;73(23):2915-2929. doi: 10.1016/j.jacc.2019.03.501.PMID: 31196447AbstractBACKGROUND:The efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.OBJECTIVES:The purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.METHODS:Randomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.RESULTS:A total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.CONCLUSIONS:Aspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.KEYWORDS:aspirin; cardiovascular events; primary preventionAssociation of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studies.Zheng Y, Li Y, Satija A, Pan A, Sotos-Prieto M, Rimm E, Willett WC, Hu FB.BMJ. 2019 Jun 12;365:l2110. doi: 10.1136/bmj.l2110.PMID: 31189526 Free Articlehttps://www.bmj.com/content/bmj/365/bmj.l2110.full.pdfAbstractOBJECTIVE:To evaluate the association of changes in red meat consumption with total and cause specific mortality in women and men.DESIGN:Two prospective cohort studies with repeated measures of diet and lifestyle factors.SETTING:Nurses' Health Study and the Health Professionals Follow-up Study, United States.PARTICIPANTS:53 553 women and 27 916 men without cardiovascular disease or cancer at baseline.MAIN OUTCOME MEASURE:Death confirmed by state vital statistics records, the national death index, or reported by families and the postal system.RESULTS:14 019 deaths occurred during 1.2 million person years of follow-up. Increases in red meat consumption over eight years were associated with a higher mortality risk in the subsequent eight years among women and men (both P for trend<0.05, P for heterogeneity=0.97). An increase in total red meat consumption of at least half a serving per day was associated with a 10% higher mortality risk (pooled hazard ratio 1.10, 95% confidence interval 1.04 to 1.17). For processed and unprocessed red meat consumption, an increase of at least half a serving per day was associated with a 13% higher mortality risk (1.13, 1.04 to 1.23) and a 9% higher mortality risk (1.09, 1.02 to 1.17), respectively. A decrease in consumption of processed or unprocessed red meat of at least half a serving per day was not associated with mortality risk. The association between increased red meat consumption and mortality risk was consistent across subgroups defined by age, physical activity, dietary quality, smoking status, or alcohol consumption.CONCLUSION:Increases in red meat consumption, especially processed meat, were associated with higher overall mortality rates.Body mass index and risk of inflammatory bowel disease: A systematic review and dose-response meta-analysis of cohort studies of over a million participants.Rahmani J, Kord-Varkaneh H, Hekmatdoost A, Thompson J, Clark C, Salehisahlabadi A, Day AS, Jacobson K.Obes Rev. 2019 Jun 12. doi: 10.1111/obr.12875. [Epub ahead of print] Review.PMID: 31190427AbstractThe relationship between body mass index (BMI) and risk of inflammatory bowel disease (IBD) is controversial. We performed a dose-response meta-analysis to investigate the association between BMI and risk of incident ulcerative colitis (UC) and Crohn's disease (CD) using prospective cohort studies. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception to January 2019. DerSimonian and Laird random-effects model was used to estimate combined hazard ratios (HRs). Overall, 882 articles were screened, and 42 full-text articles were reviewed for inclusion using the study eligibility criteria. Five studies evaluated the association between BMI and IBD with 1 044 517 participants. Pooled results showed a significant association between participants affected by obesity and risk of CD (HR: 1.42, 95% CI: 1.18-1.71, I2 : 0.00). There was a significant nonlinear association between BMI and risk of CD (P = .01, coeff = 0.5024). Pooled results did not show any significant association between being underweight and risk of UC (HR: 1.07, 95% CI: 0.96-1.19, I2 : 0.00) or CD (HR: 1.11, 95% CI: 0.93-1.31, I2 : 12.8). There was no difference in the risk for UC among participants affected by obesity compared with participants categorized as having normal BMI (HR: 0.96, 95% CI: 0.80-1.14, I2 : 8.0). This systematic review and meta-analysis identified significant dose-response relationship between being affected by obesity, as a risk factor, and incidence of CD.KEYWORDS:Crohn's disease; body mass index; inflammatory bowel disease; ulcerative colitisSerum Sodium and Pulse Pressure in SPRINT.Nowak KL, Chonchol M, Jovanovich A, You Z, Bates J, Foy C, Glasser S, Killeen AA, Kostis J, Rodriguez CJ, Segal M, Simmons DL, Taylor A, Lovato LC, Ambrosius WT, Supiano MA; SPRINT Research Group.Am J Hypertens. 2019 Jun 11;32(7):649-656. doi: 10.1093/ajh/hpz055.PMID: 30977767https://academic.oup.com/ajh/article/32/7/649/5449002AbstractBACKGROUND:High dietary sodium intake may induce a small, yet physiologically relevant rise in serum sodium concentration, which associates with increased systolic blood pressure. Cellular data suggest that this association is mediated by increased endothelial cell stiffness. We hypothesized that higher serum sodium levels were associated with greater arterial stiffness in participants in the Systolic Blood Pressure Intervention Trial (SPRINT).METHODS:Multivariable linear regression was used to examine the association between baseline serum sodium level and (i) pulse pressure (PP; n = 8,813; a surrogate measure of arterial stiffness) and (ii) carotid-femoral pulse wave velocity (CFPWV; n = 591 in an ancillary study to SPRINT).RESULTS:Baseline mean ± SD age was 68 ± 9 years and serum sodium level was 140 ± 2 mmol/L. In the PP analysis, higher serum sodium was associated with increased baseline PP in the fully adjusted model (tertile 3 [≥141 mmol] vs. tertile 2 [139-140 mmol]; β = 0.87, 95% CI = 0.32 to 1.43). Results were similar in those with and without chronic kidney disease. In the ancillary study, higher baseline serum sodium was not associated with increased baseline CFPWV in the fully adjusted model (β = 0.35, 95% CI = -0.14 to 0.84).CONCLUSIONS:Among adults at high risk for cardiovascular events but free from diabetes, higher serum sodium was independently associated with baseline arterial stiffness in SPRINT, as measured by PP, but not by CFPWV. These results suggest that high serum sodium may be a marker of risk for increased PP, a surrogate index of arterial stiffness.KEYWORDS:CKD; blood pressure; electrolyte imbalances; hypernatremia; hypertension; pulse pressure; pulse-wave velocityEffects of ad libitum consumed, low-fat, high-fiber plant-based diet supplemented with plant-based meal replacements on cardiovascular risk factors.Jakše B, Jakše B, Pajek J, Pajek M.Food Nutr Res. 2019 May 21;63. doi: 10.29219/fnr.v63.1560. eCollection 2019.PMID: 31191190AbstractBACKGROUND:Sustainable nutritional strategies to reduce risk factors of cardiovascular diseases are highly needed. Inclusion of meal replacements may increase adherence to plant-based diets (PBDs).OBJECTIVE:The aim of this study was to test the effects of a transition from a western-type diet to a new nutritional paradigm with a PBD from predominately unrefined whole food sources, eaten ad libitum and including nutrient-enriched plant-based meal replacements twice daily.DESIGN:This was a single-arm, prospective interventional trial for 10 weeks in 36 participants with extension to 36 weeks in 18 participants. The main endpoint was serum low-density lipoprotein (LDL)-cholesterol measured at baseline, after 10 weeks (phase 1), and after 36 weeks (phase 2). Secondary endpoints included total, non-high-density lipoprotein (HDL) and HDL-cholesterol, fasting glucose, uric acid, and insulin-like growth factor-1 (IGF-1).RESULTS:The mean reduction in LDL-cholesterol was 0.6 (95% confidence interval [CI], 0.3-0.8) mmol/L (-15%, P < 0.001) at the end of phase 1, with no further change by the end of phase 2. Similar reductions were noted for non-HDL-cholesterol and total cholesterol. HDL-cholesterol was reduced by 0.16 mmol/L (95% CI, 0.1-0.2). There was a borderline reduction in fasting glucose (5.2 to 5 mmol/L in phase 1, P = 0.08) and a small significant rise in serum uric acid levels of 15 (95% CI, 1-28) μmol/L, P < 0.05. Median baseline value for IGF-1 concentration was 156 μg/L. Participants with baseline IGF-1 below median had a significant increase in IGF-1 value from baseline 110 ± 31 to 132 ± 39 at the end of phase 1 (mean change of +22 μg/L, 95% CI, 11-33, P = 0.001). Participants with baseline IGF-1 above median had no significant change in IGF-1. Significant reductions in body weight, body fat, and visceral fat were observed.CONCLUSIONS:Supplemented, unrefined PBD eaten ad libitum was effective in improving total and LDL-cholesterol, non-HDL-cholesterol, and IGF-1 in low baseline IGF-1 subgroup.KEYWORDS:atherosclerosis; cholesterol; fat; nutrition; obesity; weight reductionTotal Fermented Dairy Food Intake Is Inversely Associated with Cardiovascular Disease Risk in Women.Buziau AM, Soedamah-Muthu SS, Geleijnse JM, Mishra GD.J Nutr. 2019 Jun 13. pii: nxz128. doi: 10.1093/jn/nxz128. [Epub ahead of print]PMID: 31192363AbstractBACKGROUND:The relation between fermented dairy consumption and type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in an Australian population remains to be established.OBJECTIVES:The aim of this study was to investigate the association between fermented dairy consumption and T2DM and CVD risk.METHODS:The Australian Longitudinal Study on Women's Health included Australian women (aged 45-50 y) at baseline in 2001, who were followed up through 5 surveys until 2016. Dietary intake was assessed through the use of a validated 101-item FFQ at baseline. Main study outcomes were self-reported physician-diagnosed T2DM and CVD. Logistic regression models adjusted for sociodemographic and lifestyle factors were used to estimate the association between dairy intake and T2DM and CVD risk.RESULTS:Of 7633 women free of diabetes at baseline, 701 (9.2%) developed T2DM during a maximum 15-y follow-up period. Women in the highest tertile of yogurt intake had lower adjusted odds of T2DM than those in the lowest tertile (OR: 0.81; 95% CI: 0.67, 0.99; P = 0.041). This relation became nonsignificant after adjustment for dietary variables and total energy intake (OR: 0.88; 95% CI: 0.71, 1.08; P = 0.21). Of 7679 women free of CVD at baseline, 835 (10.9%) cases of CVD were reported during follow-up. High intake of yogurt and total fermented dairy was associated with lower CVD risk (OR: 0.84; 95% CI: 0.70, 1.00; P = 0.05, 0.80; 0.67, 0.96; 0.017, respectively) than observed in the lowest tertile of dairy product intake. Additional adjustment attenuated the relation (OR: 0.87; 95% CI: 0.72, 1.04; P = 0.13, 0.83; 0.69, 1.00; 0.048, for yogurt and total fermented dairy, respectively). No associations were found with other dairy groups.CONCLUSION:The findings from this population-based study of Australian women suggest an inverse association between total fermented dairy intake and CVD risk, which may partly be accounted for by other dietary components.KEYWORDS:Australia; cardiovascular disease; cheese; coronary heart disease; dairy; fermented dairy; stroke; type 2 diabetes mellitus; women's health; yogurtEffects of dietary and physical activity interventions on the risk of type 2 diabetes in South Asians: meta-analysis of individual participant data from randomised controlled trials.Jenum AK, Brekke I, Mdala I, Muilwijk M, Ramachandran A, Kjøllesdal M, Andersen E, Richardsen KR, Douglas A, Cezard G, Sheikh A, Celis-Morales CA, Gill JMR, Sattar N, Bhopal RS, Beune E, Stronks K, Vandvik PO, van Valkengoed IGM.Diabetologia. 2019 Jun 15. doi: 10.1007/s00125-019-4905-2. [Epub ahead of print] Review.PMID: 31201437AbstractAIMS/HYPOTHESIS:Individuals of South Asian origin have a high risk of type 2 diabetes and of dying from a diabetes-attributable cause. Lifestyle modification intervention trials to prevent type 2 diabetes in high-risk South Asian adults have suggested more modest effects than in European-origin populations. The strength of the evidence of individual studies is limited, however. We performed an individual participant data meta-analysis of available RCTs to assess the effectiveness of lifestyle modification in South Asian populations worldwide.METHODS:We searched PubMed, EMBASE, Cochrane Library and Web of Science (to 24 September 2018) for RCTs on lifestyle modification interventions incorporating diet and/or physical activity in South Asian adults. Reviewers identified eligible studies and assessed the quality of the evidence. We obtained individual participant data on 1816 participants from all six eligible trials (four from Europe and two from India). We generated HR estimates for incident diabetes (primary outcome) and mean differences for fasting glucose, 2 h glucose, weight and waist circumference (secondary outcomes) using mixed-effect meta-analysis overall and by pre-specified subgroups. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence of the estimates. The study is registered with the International Prospective Register of Systematic Reviews ([PROSPERO] CRD42017078003).RESULTS:Incident diabetes was observed in 12.6% of participants in the intervention groups and in 20.0% of participants in the control groups. The pooled HR for diabetes incidence was 0.65 (95% CI 0.51, 0.81; I2 = 0%) in intervention compared with control groups. The absolute risk reduction was 7.4% (95% CI 4.0, 10.2), with no interactions for the pre-specified subgroups (sex, BMI, age, study duration and region where studies were performed). The quality of evidence was rated as moderate. Mean difference for lifestyle modification vs control groups for 2 h glucose was -0.34 mmol/l (95% CI -0.62, -0.07; I2 = 50%); for weight -0.75 kg (95% CI -1.34, -0.17; I2 = 71%) and for waist -1.16 cm (95% CI -2.16, -0.16; I2 = 75%). No effect was found for fasting glucose. Findings were similar across subgroups, except for weight for European vs Indian studies (-1.10 kg vs -0.08 kg, p = 0.02 for interaction).CONCLUSIONS/INTERPRETATION:Despite modest changes for adiposity, lifestyle modification interventions in high-risk South Asian populations resulted in a clinically important 35% relative reduction in diabetes incidence, consistent across subgroups. If implemented on a large scale, lifestyle modification interventions in high-risk South Asian populations in Europe would reduce the incidence of diabetes in these populations.KEYWORDS:Diet; Individual participant data meta-analysis; Lifestyle intervention; Physical activity; Prevention; RCT; South Asians; Type 2 diabetes
  5. AlPater

    Al's CR updates

    Mammary protein synthesis upon long-term nutritional restriction was attenuated by oxidative stress induced inhibition of v-ATPase/mTORC1 signaling. Zhong H, Song Y, Wang P, Feng B, Zhang X, Che L, Lin Y, Xu S, Li J, Wu, Fang Z. J Agric Food Chem. 2019 Jun 13. doi: 10.1021/acs.jafc.9b02170. [Epub ahead of print] PMID: 31189310 Abstract To determine how nutritional restriction compromised milk synthesis, sows were fed 100% (control) or 76% (restricted) of the recommended feed allowance from postpartum day (PD)-1 to PD-28. Compared with the control, more body reserves loss, increased plasma triglyceride and high-density lipoprotein cholesterol levels while decreased plasma methionine concentrations were observed in the restricted group at PD-21. The increased plasma malondialdehyde level while decreased plasma histidine, taurine concentrations and decreased glutathione peroxidase activity were observed at PD-28 when backfat loss further increased in the restricted group. In mammary glands, the vacuolar H+-adenosine triphosphatase (v-ATPase), as the upstream of mechanistic target of rapamycin (mTOR) signaling, showed decreased activity, while phosphorylation of mTOR, S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1, and β-casein abundance were all decreased following feed restriction. Altogether, long-term nutrition restriction could induce progressively aggravated oxidative stress and compromise mammary protein synthesis through repression of v-ATPase/mTORC1 signaling. Calorie restriction with regular chow, but not a high-fat diet, delays onset of spontaneous osteoarthritis in the Hartley guinea pig model. Radakovich LB, Marolf AJ, Culver LA, Santangelo KS. Arthritis Res Ther. 2019 Jun 13;21(1):145. doi: 10.1186/s13075-019-1925-8. PMID: 31196172 https://arthritis-research.biomedcentral.com/track/pdf/10.1186/s13075-019-1925-8 Abstract BACKGROUND: Obesity is a leading risk factor for osteoarthritis (OA). In contrast, calorie restriction (CR) may lessen OA due to improved systemic inflammatory status and reduced weight-bearing. The aim of this study was to determine how CR with regular chow versus a high-fat diet (HFD) alters OA progression using the Hartley guinea pig model of disease. METHODS: Twenty-four male guinea pigs were allocated to four groups at 2 months of age: (1) ad libitum regular chow (obese), (2) CR regular chow (lean), (3) ad libitum HFD, and (4) CR HFD. Animals in both HFD groups ate identical amounts and were combined into one HFD group for analyses. At 5 months, hind limbs were harvested for microcomputed tomography (microCT) and histopathologic evaluation of knee OA. Total body, gonad fat, and infrapatellar fat pad (IFP) masses were recorded. IFPs were collected for gene expression analysis. Immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1) was performed on intact joints. Serum was utilized for protein C3 measurement. All data were compared using ordinary one-way ANOVA analyses with Tukey's post-hoc tests. RESULTS: Body mass in the lean and HFD groups were similar and lower than the obese group. Despite this, gonad fat pads in the HFD group were comparable to the obese group. MicroCT and histologic OA scores were similar in obese and HFD groups; both scores were significantly lower in the lean group. Obese and HFD groups displayed increased gene expression of pro-inflammatory and catabolic mediators in IFPs relative to lean animals. Consistent with this, immunohistochemistry for MCP-1 in knee joints demonstrated strong positive staining in obese and HFD groups but was minimally detected in lean animals. Serum protein C3 levels were also statistically higher. CONCLUSIONS: This study demonstrated that CR with a regular chow diet lessened knee OA in the Hartley guinea pig and was associated with decreased local and systemic inflammation compared to obese animals. HFD animals, although under CR conditions, had OA scores and inflammatory markers similar to obese animals. Thus, diet composition, and not solely body weight, may be a key factor in development of OA. KEYWORDS: Calorie restriction; Hartley guinea pig; High-fat diet; Obesity; Osteoarthritis Cognitive Effects of Adding Caloric Restriction to Aerobic Exercise Training in Older Adults with Obesity. Hugenschmidt CE, Leng X, Lyles M, Michael L, Dougherty A, Babcock P, Baker LD, Brinkley TE, Nicklas BJ. Obesity (Silver Spring). 2019 Jun 14. doi: 10.1002/oby.22525. [Epub ahead of print] PMID: 31199592 Abstract OBJECTIVE: This study examined the short- and long-term effects of adding caloric restriction to 5 months of aerobic exercise training on executive function in sedentary older adults with obesity. METHODS: Sedentary adults with obesity aged 65 to 79 years completed a randomized trial investigating the cardiorespiratory benefits of adding moderate (~ 250 kcal) or high (~ 600 kcal) caloric restriction to a 20-week aerobic exercise program. Approximately half (n = 88) completed a cognitive assessment battery at baseline, post intervention, and 18 to 24 months after intervention completion. The primary outcome was an executive function composite score. RESULTS: In the overall sample, the executive function composite increased 0.114 from baseline to postintervention (P = 0.01). Randomization to caloric restriction did not significantly alter executive function over aerobic exercise alone, nor were there between-group differences on any individual executive function test following the intervention or at long-term follow-up. Adding caloric restriction to exercise was associated with a modest increase in Mini-Mental State Examination score (P = 0.04). In the overall sample, increases from baseline at long-term follow-up were noted in digit symbol and word list recall performance as well. CONCLUSIONS: Adding caloric restriction to a 20-week aerobic exercise program does not worsen or improve executive function more than exercise alone assessed up to 24 months post randomization. Age- and Experience-Related Plasticity of ATP-Mediated Signaling in the Neocortex. Lalo U, Bogdanov A, Pankratov Y. Front Cell Neurosci. 2019 May 29;13:242. doi: 10.3389/fncel.2019.00242. eCollection 2019. PMID: 31191257 [pdf availed from PMID site.] Abstract There is growing recognition of the important role of interaction between neurons and glial cells for brain longevity. The extracellular ATP have been shown to bring significant contribution into bi-directional glia-neuron communications, in particular into astrocyte-driven modulation of synaptic plasticity. To elucidate a putative impact of brain aging on neuron-glia networks, we explored the aging-related plasticity of the purinoreceptors-mediated signaling in cortical neurons and astrocytes. We investigated the age- and experience-related alterations in purinergic components of neuronal synaptic currents and astroglial calcium signaling in the layer2/3 of neocortex of mice exposed to the mild caloric restriction (CR) and environmental enrichment (EE) which included ad libitum physical exercise. We observed the considerable age-related decline in the neuronal P2X receptor-mediated miniature spontaneous currents which originated from the release of ATP from both synapses and astrocytes. We also found out that purinergic astrocytic Ca2+-signaling underwent the substantial age-related decline but EE and CR rescued astroglial signaling, in particular mediated by P2X1, P2X1/5, and P2Y1 receptors. Our data showed that age-related attenuation in the astroglial calcium signaling caused a substantial decrease in the exocytosis of ATP leading to impairment of astroglia-derived purinergic modulation of excitatory synaptic currents and GABAergic tonic inhibitory currents. On a contrary, exposure to EE and CR, which enhanced purinergic astrocytic calcium signaling, up-regulated the excitatory and down-regulated the inhibitory currents in neurons of old mice, thus counterbalancing the impact of aging on synaptic signaling. Combined, our results strongly support the physiological importance of ATP-mediated signaling for glia-neuron interactions and brain function. Our data also show that P2 purinoreceptor-mediated communication between astrocytes and neurons in the neocortex undergoes remodeling during brain aging and decrease in the ATP release may contribute to the age-related impairment of synaptic transmission. KEYWORDS: AMPA receptor; GABA receptor A; ageing; calcium; diet; exercise; glia-neuron interaction; synaptic strength
  6. Dietary glycemic index, glycemic load, and risk of mortality from all causes and cardiovascular diseases: a systematic review and dose-response meta-analysis of prospective cohort studies. Shahdadian F, Saneei P, Milajerdi A, Esmaillzadeh A. Am J Clin Nutr. 2019 Jun 12. pii: nqz061. doi: 10.1093/ajcn/nqz061. [Epub ahead of print] PMID: 31187856 Abstract BACKGROUND: Previous findings on the association of dietary glycemic index (GI) and glycemic load (GL) with mortality are conflicting. OBJECTIVES: The aim of this study was to summarize earlier findings on the association between dietary GI and GL and the risk of cardiovascular disease (CVD) and all-cause mortality. METHODS: A comprehensive literature search was performed of electronic databases, including MEDLINE (PubMed), Scopus, ISI Web of Science, EMBASE, and Google scholar, up to September 2018. Prospective cohort studies that reported GI and GL as the exposure and all-cause or CVD mortality as the outcome were included in the analysis. The random-effects model was used to estimate pooled RR and 95% CIs of all-cause and CVD mortality. RESULTS: Eighteen cohort studies with a total of 251,497 participants, reporting 14,774 cases of all-cause mortality and 3658 cases of CVD mortality, were included in the present analysis. No significant association was found between dietary GI and all-cause mortality (RR: 1.07; 95% CI: 0.96, 1.19) and CVD mortality (RR: 1.02; 95% CI: 0.87, 1.20). In addition, dietary GL was not associated with all-cause mortality (RR: 1.08; 95% CI: 0.93, 1.27) or CVD mortality (RR: 1.07; 95% CI: 0.92, 1.25). However, the highest dietary GI, in comparison to the lowest one, significantly increased the risk of all-cause mortality in women (RR: 1.17; 95% CI: 1.02, 1.35). No evidence for a nonlinear association between dietary GI or GL and all-cause and CVD mortality was found (P > 0.05). CONCLUSIONS: This meta-analysis of prospective cohort studies showed no significant association between either dietary GI or GL and all-cause and CVD mortality in men, but a positive association of GI with all-cause mortality in women. KEYWORDS: CVD mortality; all-causes mortality; glycemic index; glycemic load; meta-analysis Adult cancer risk in women who were breastfed as infants: large UK prospective study. Yang TO, Cairns BJ, Green J, Reeves GK, Floud S, Bradbury KE, Beral V; Million Women Study Collaborators. Eur J Epidemiol. 2019 Jun 11. doi: 10.1007/s10654-019-00528-z. [Epub ahead of print] PMID: 31187313 Abstract There are known short-term benefits in breastfed infants versus bottle-fed infants in terms of lower risks of infection and obesity in infancy and childhood, but the long-term effect on the risk of adult cancers is unclear. In a cohort of 1 in 4 UK women born in 1935-1950 we report the incidence of adult cancers in relation to having been breastfed in infancy. In median year 2001 (interquartile range 2000-2003) 548,741 women without prior cancer reported whether they had been breastfed. There was 81% agreement between women's report of having been breastfed and information on breastfeeding recorded when they were 2 years old. Participants were followed by record-linkage to national cancer registration, hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CI) by having been breastfed or not for eight cancer sites with > 2000 incident cases and for related conditions, where appropriate. Of the eight cancers examined here one association was highly statistically significant: an increase in colorectal cancer incidence among women who had been breastfed versus not (RR 1.18, 95% CI 1.12-1.24, n = 8651). To investigate further the findings for colorectal cancer, we studied eight other gastro-intestinal conditions, and found increased risks in women who had been breastfed versus not for benign colorectal polyps (RR 1.09, 95% CI 1.05-1.13, n = 17,677) and for appendicitis (RR 1.19, 95% CI 1.07-1.31, n = 2108). The greater risks of adult colorectal cancer, colorectal polyps and appendicitis associated with having been breastfed in infancy suggest possible long-term effects of infant feeding practices on the gastrointestinal tract. Further studies are required to clarify this novel association. KEYWORDS: Breast cancer; Breast milk; Colorectal cancer; Infant feeding
  7. Time-restricted feeding delays the emergence of the age-associated, neoplastic-prone tissue landscape. Serra M, Marongiu F, Pisu MG, Serra M, Laconi E. Aging (Albany NY). 2019 Jun 12. doi: 10.18632/aging.102021. [Epub ahead of print] PMID: 31188781 https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/dxZSX3zGcxpqLhW4T.pdf Abstract Aging increases the risk of cancer partly through alterations in the tissue microenvironment. Time-restricted feeding (TRF) is being proposed as an effective strategy to delay biological aging. In the present studies, we assessed the effect of long-term exposure to TRF on the emergence of the age-associated, neoplastic-prone tissue landscape. Animals were exposed to either ad libitum feeding (ALF) or TRF for 18 months and then transplanted with hepatocytes isolated from pre-neoplastic nodules. Both groups were continued ALF and the growth of transplanted cells was evaluated 3 months later. A significant decrease in frequency of larger size clusters of pre-neoplastic hepatocytes was seen in TRF-exposed group compared to controls. Furthermore, TRF modified several parameters related to both liver and systemic aging towards the persistence of a younger phenotype, including a decrease in liver cell senescence, diminished fat accumulation and up-regulation of SIRT1 in the liver, down-regulation of plasma IGF-1, decreased levels of plasma lipoproteins and up-regulation of hippocampal brain-derived growth factor (BDNF).These results indicate that TRF was able to delay the onset of the neoplastic-prone tissue landscape typical of aging. To our knowledge, this is the first investigation to describe a direct beneficial effect of TRF on early phases of carcinogenesis. KEYWORDS: aging; carcinogenesis; time restricted feeding; tissue microenvironment
  8. Associations Between Linoleic Acid Intake and Incident Type 2 Diabetes Among U.S. Men and Women. Zong G, Liu G, Willett WC, Wanders AJ, Alssema M, Zock PL, Hu FB, Sun Q. Diabetes Care. 2019 Jun 10. pii: dc190412. doi: 10.2337/dc19-0412. [Epub ahead of print] PMID: 31182488 Abstract OBJECTIVE: To investigate the association between intakes of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk in three prospective cohort studies of U.S. men and women. RESEARCH DESIGN AND METHODS: We followed 83,648 women from the Nurses' Health Study (NHS; 1980-2012), 88,610 women from NHSII (1991-2013, and 41,771 men from the Health Professionals Follow-Up Study (1986-2012). Dietary data was collected every 2-4 years by using validated food-frequency questionnaires. Self-reported incident diabetes, identified biennially, was confirmed by using a validated supplementary questionnaire. RESULTS: During 4.93 million person-years of follow-up, 18,442 type 2 diabetes cases were documented. Dietary n-6 PUFAs accounted for 4.4-6.8% of total energy, on average, and consisted primarily of linoleic acid (LA; ≥98%). In multivariate-adjusted models, hazard ratios (95% CIs) of type 2 diabetes risk comparing extreme n-6 PUFA quintiles (highest vs. lowest) were 0.91 (0.85, 0.96; P trend = 0.002) for total n-6 PUFAs and 0.92 (0.87, 0.98; P trend = 0.01) for LA. In an isocaloric substitution model, diabetes risk was 14% (95% CI 5%, 21%; P = 0.002) lower when LA isocalorically replaced saturated fats (5% of energy), 17% (95% CI 9%, 24%; P < 0.001) lower for trans fats (2% energy), or 9% (95% CI 17%, 0.1%; P = 0.047) lower for carbohydrates (5% energy). Replacing n-3 PUFAs or monounsaturated fats with LA was not significantly associated with type 2 diabetes risk. CONCLUSIONS: Our study provides additional evidence that LA intake is inversely associated with risk of type 2 diabetes, especially when replacing saturated fatty acids, trans fats, or carbohydrates. Dietary Glycemic Index and Glycemic Load and the Risk of Prostate Cancer: An Updated Systematic Review and Dose-Response Meta-Analysis. Sadeghi A, Sadeghi O, Khodadost M, Pirouzi A, Hosseini B, Saedisomeolia A. Nutr Cancer. 2019 Jun 11:1-10. doi: 10.1080/01635581.2019.1621356. [Epub ahead of print] PMID: 31184513 https://sci-hub.tw/10.1080/01635581.2019.1621356 Abstract A meta-analysis in 2015 revealed no significant association between glycemic index (GI), glycemic load (GL), and prostate cancer. Moreover, until now, no study has examined the dose-response association of GI, GL, and prostate cancer yet. The online databases were searched by two independent researchers for relevant publications up to Jan. 2019, using relevant keywords. Nine studies including five prospective and four case-control studies were included in the current systematic review and meta-analysis. These studies have included 290,911 individuals. We found a significant positive dose-response association between dietary GI and prostate cancer (Pnonlinearity = 0.03). Comparing individuals in the highest category of GI with those in the lowest category, no significant association was found between GI and prostate cancer (combined effect size: 1.08, 95% CI: 0.97-1.19, P = 0.17). Furthermore, no significant association was seen between dietary GL and prostate cancer in both dose-response analysis and when comparing the highest versus lowest categories of GL (combined effect size: 1.03, 95% CI: 0.91-1.16, P = 0.65). In conclusion, we found a significant positive dose-response association between dietary GI and prostate cancer. However, significant association was not seen for dietary GL. Metformin prevents murine ovarian aging. Qin X, Du D, Chen Q, Wu M, Wu T, Wen J, Jin Y, Zhang J, Wang S. Aging (Albany NY). 2019 Jun 10. doi: 10.18632/aging.102016. [Epub ahead of print] PMID: 31182682 Abstract A number of studies have shown that metformin can delay aging process and extend healthy lifespan in animals. However, its role in female reproductive lifespan is unclear. This study was aimed to explore the potential anti-aging effect of metformin on the ovary and its possible mechanisms. Female C57BL/6 mice of 27-week old were divided into two groups, the control group (CON) and metformin-treated group (MET). CON mice were fed ad libitum, while MET mice were fed on chows supplied with 100mg/kg metformin for half a year. Ovarian reserve and function were assessed by ovarian follicle counts, estrous cycle and sex hormones levels. The expressions of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), and ovarian aging associated proteins P16, SIRT1, p-rpS6 and Bcl2 were examined. The MET mice exhibited increased level of serum E2 hormone and higher percentage of regular estrous cycles after 6 months' feeding, compared to the CON mice. The amount of primordial and primary follicles and the expression of SIRT1 were significantly increased, but the levels of P16, 8-OHdG, 4-HNE and p-rpS6 were decreased in the MET mice. These results indicate that metformin can delay ovarian aging process, probably by inducing the expression of SIRT1 and reducing the oxidative damage. KEYWORDS: SIRT1; metformin; ovarian aging; oxidative stress When battling high blood cholesterol, white meat is no better than red meat, study says Research followed 113 people on controlled diets to garner results contradicting conventional wisdom CBC News · Posted: Jun 11, 2019 https://www.cbc.ca/news/health/health-white-meat-red-meat-cholesterol-science-1.5168534 >>>>>>>>>>>>>>>>>>>>>>>> Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial. Bergeron N, Chiu S, Williams PT, M King S, Krauss RM. Am J Clin Nutr. 2019 Jun 4. pii: nqz035. doi: 10.1093/ajcn/nqz035. [Epub ahead of print] PMID: 31161217 https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqz035/5494812 https://watermark.silverchair.com/nqz035.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlAwggJMBgkqhkiG9w0BBwagggI9MIICOQIBADCCAjIGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMasb8QHNzeTgS8ccEAgEQgIICA_Q13ymYNFRljhS_NilkiErxI_SnuwbC6-7bcNiI3G2ShO_WGAql0vw2STPzEIXbB8ek9S37-RUXiP6z57B200jGbv-bl_EouHSOlvmMfvUQ2FbI_xmH84LfEf5f8h-Mv7m65RSEzTrGWZptlaX84Pko0_ql_97PB7rswTGtjchY6mWvxVmtjjLfANuAYgoxAdktXbFenbmVFskpn7W5MgqNwnlby-jRUtv03k2zhWGv98i9RSLMwlBa8bebzlDDe7eXIjuPCaM6h1kI9WuEhbGGseGNZAHxJpm3wcbXkJnlNZnR7Pg44aUsOT8c8j7tQPlfXLEA7EYTeIzBS4tXzETuCtiHQeVi1OtUTNSC83MIGWExclAk-SlsadFzwPurlkwqrTYmkBlCM07veK0rYWQgLiwttd_y7bKpSe6DdxZx15i7NrjnbIGMXidb8zMib8hoeSEHTdhwPuyZRmmeuUqyIZFjtnR0FRkAm-0HGuab4HPlQNZLDCX1EFeiaxImlDy2kCNj9hyhJnXWU_G4vpeIjU8_ZVezuibK1ib8N0pkVNo9EwvldyNCsF_tA6lSvkgIoR7KzqroLrm9sP5nYEnbRHhjipUzRM2WOJj-nYSEgZmW86y75X-b6zwDbZFQYNGJv3KylQrtC6hV6cVNG1cHEL1EyZxN5rvDbTJmOhombhvf Abstract BACKGROUND: Dietary recommendations to limit red meat are based on observational studies linking intake to cardiovascular disease (CVD) risk together with the potential of its saturated fatty acid (SFA) content to raise low-density lipoprotein (LDL) cholesterol. However, the relation of white meat to CVD risk, and the effects of dietary protein source on lipoprotein particle subfractions, have not been extensively evaluated. OBJECTIVE: We tested whether levels of atherogenic lipids and lipoproteins differed significantly following consumption of diets with high red meat content compared with diets with similar amounts of protein derived from white meat or nonmeat sources, and whether these effects were modified by concomitant intake of high compared with low SFAs. METHODS: Generally healthy men and women, 21-65 y, body mass index 20-35 kg/m2, were randomly assigned to 1 of 2 parallel arms (high or low SFA) and within each, allocated to red meat, white meat, and nonmeat protein diets consumed for 4 wk each in random order. The primary outcomes were LDL cholesterol, apolipoprotein B (apoB), small + medium LDL particles, and total/high-density lipoprotein cholesterol. RESULTS: Analysis included participants who completed all 3 dietary protein assignments (61 for high SFA; 52 for low SFA). LDL cholesterol and apoB were higher with red and white meat than with nonmeat, independent of SFA content (P < 0.0001 for all, except apoB: red meat compared with nonmeat [P = 0.0004]). This was due primarily to increases in large LDL particles, whereas small + medium LDL and total/high-density lipoprotein cholesterol were unaffected by protein source (P = 0.10 and P = 0.51, respectively). Primary outcomes did not differ significantly between red and white meat. Independent of protein source, high compared with low SFA increased LDL cholesterol (P = 0.0003), apoB (P = 0.0002), and large LDL (P = 0.0002). CONCLUSIONS: The findings are in keeping with recommendations promoting diets with a high proportion of plant-based food but, based on lipid and lipoprotein effects, do not provide evidence for choosing white over red meat for reducing CVD risk. This trial was registered at Clinicaltrials.gov as NCT01427855. KEYWORDS: beef; chicken; dairy fat; dietary recommendations; lipoprotein particle distribution; plant protein; poultry; vegetable protein
  9. AlPater

    Al's CR updates

    Acute but Not Chronic Calorie Restriction Defends against Stress-Related Anxiety and Despair in a GHS-R1a-Dependent Manner. Lu Y, Niu M, Qiu X, Cao H, Xing B, Sun Y, Zhou Z, Zhou Y. Neuroscience. 2019 Jun 8. pii: S0306-4522(19)30398-7. doi: 10.1016/j.neuroscience.2019.05.067. [Epub ahead of print] PMID: 31185255 Abstract Ghrelin is an important orexigenic brain-gut hormone that regulates feeding, metabolism and glucose homeostasis in human and rodents at multiple levels. Ghrelin functions by binding to its receptor, the growth hormone secretagogue receptor 1a (GHS-R1a), which is widely expressed both inside and outside of the brain. Both acute and chronic calorie restriction (CR) were reported to increase endogenous ghrelin levels and lead to beneficial effects on brain functions, including anti-anxiety effects, anti-depressive effects, and memory improvement. However, the causal relationship and underlying mechanisms are not fully understood. Here, we introduced acute or chronic CR to both GHS-R1a KO (Ghsr-/-) mice and WT (Ghsr+/+) littermates, and investigated anxiety- and despair-related behaviors in the elevated plus maze (EPM), open field (OF) and forced swimming (FS) tests. We found that acute and chronic CR produced similar anxiolytic and anti-despair responses in Ghsr+/+ mice but opposite responses in Ghsr-/- mice. In particular, acute CR enhanced while chronic CR reduced anxiety- and despair-like behaviors in Ghsr-/- mice. Acute CR triggered anxiolytic and anti-despair responses in Ghsr+/+ mice. This effect was abolished by a GHS-R1a antagonist, suggesting a GHS-R1a dependent mechanism. Ad-libitum refeeding masked behavioral responses induced by acute CR in both Ghsr-/- and Ghsr+/+ mice. Altogether, our findings indicate that acute and chronic CR mitigate anxiety- and despair-like behaviors with different physiological mechanisms, with the former being dependent on endogenous ghrelin release and GHS-R1a signaling, while the latter may not be. KEYWORDS: GHS-R1a; anxiety; behaviors; calorie restriction; depression; ghrelin; mice; stress
  10. Impact of dietary protein intake and obesity on lean mass in middle-aged individuals after a 12-year follow-up: The Korean Genome and Epidemiology Study (KoGES). So E, Choi SK, Joung H. Br J Nutr. 2019 Jun 10:1-21. doi: 10.1017/S000711451900117X. [Epub ahead of print] PMID: 31177993 Abstract This study investigated the association between protein intake and lean mass according to obesity status over a 12-year period. Data on 4,412 participants aged 40-69 years were obtained from the Korean Genome and Epidemiology Study. The usual dietary protein intake of these participants was assessed at baseline using a semi-quantitative food frequency questionnaire. Body composition was measured using a bioelectrical impedance analysis at baseline and after a 12-year follow-up. Linear mixed effects models were used to examine the associations between lean mass after a 12-year follow-up and protein intake at baseline. After adjusting for covariates and lean mass at baseline, comparisons between the highest and lowest tertiles revealed that dietary protein intake was positively associated with lean mass in both men (β=0.79, p=0.001) and women (β=0.28, p=0.082) after the 12-year period; however, those differences were attenuated after additional adjustment for fat mass at baseline and were stronger in the normal-weight group (men, β=0.85, p=0.002; women, β=0.97, p&lt;0.001) but were not detected in the obese group. In the obese group, age (men, β=4.08, p&lt;0.001; women, β=2.61, p&lt;0.001) and regular physical activity (men, β=0.88, p=0.054; women, β=0.76, p&lt;0.001) were significantly associated with lean mass after 12 years of follow-up. The results of this study showed that protein intake may contribute to the prevention of ageing-related lean mass loss; however, the impact of this intake may vary depending on obesity status. Therefore, the maintenance of a healthy body weight during ageing through enhanced protein intake is likely to confer health benefits. KEYWORDS: Korean Genome and Epidemiology Study (KoGES); cohort study; lean mass; obesity; protein intake Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases. Chaix A, Manoogian ENC, Melkani GC, Panda S. Annu Rev Nutr. 2019 Jun 10. doi: 10.1146/annurev-nutr-082018-124320. [Epub ahead of print] PMID: 31180809 https://sci-hub.tw/10.1146/annurev-nutr-082018-124320 Abstract Molecular clocks are present in almost every cell to anticipate daily recurring and predictable changes, such as rhythmic nutrient availability, and to adapt cellular functions accordingly. At the same time, nutrient-sensing pathways can respond to acute nutrient imbalance and modulate and orient metabolism so cells can adapt optimally to a declining or increasing availability of nutrients. Organismal circadian rhythms are coordinated by behavioral rhythms such as activity-rest and feeding-fasting cycles to temporally orchestrate a sequence of physiological processes to optimize metabolism. Basic research in circadian rhythms has largely focused on the functioning of the self-sustaining molecular circadian oscillator, while research in nutrition science has yielded insights into physiological responses to caloric deprivation or to specific macronutrients. Integration of these two fields into actionable new concepts in the timing of food intake has led to the emerging practice of time-restricted eating. In this paradigm, daily caloric intake is restricted to a consistent window of 8-12 h. This paradigm has pervasive benefits on multiple organ systems. Methionine is a metabolic dependency of tumor-initiating cells. Wang Z, Yip LY, Lee JHJ, Wu Z, Chew HY, Chong PKW, Teo CC, Ang HY, Peh KLE, Yuan J, Ma S, Choo LSK, Basri N, Jiang X, Yu Q, Hillmer AM, Lim WT, Lim TKH, Takano A, Tan EH, Tan DSW, Ho YS, Lim B, Tam WL. Nat Med. 2019 May;25(5):825-837. doi: 10.1038/s41591-019-0423-5. Epub 2019 May 6. Erratum in: Nat Med. 2019 May 21;:. PMID: 31061538 https://sci-hub.tw/10.1038/s41591-019-0423-5 Abstract Understanding cellular metabolism holds immense potential for developing new classes of therapeutics that target metabolic pathways in cancer. Metabolic pathways are altered in bulk neoplastic cells in comparison to normal tissues. However, carcinoma cells within tumors are heterogeneous, and tumor-initiating cells (TICs) are important therapeutic targets that have remained metabolically uncharacterized. To understand their metabolic alterations, we performed metabolomics and metabolite tracing analyses, which revealed that TICs have highly elevated methionine cycle activity and transmethylation rates that are driven by MAT2A. High methionine cycle activity causes methionine consumption to far outstrip its regeneration, leading to addiction to exogenous methionine. Pharmacological inhibition of the methionine cycle, even transiently, is sufficient to cripple the tumor-initiating capability of these cells. Methionine cycle flux specifically influences the epigenetic state of cancer cells and drives tumor initiation. Methionine cycle enzymes are also enriched in other tumor types, and MAT2A expression impinges upon the sensitivity of certain cancer cells to therapeutic inhibition.
  11. AlPater

    Al's CR updates

    Calorie restriction activates new adult born olfactory-bulb neurones in a ghrelin-dependent manner but acyl-ghrelin does not enhance sub-ventricular zone neurogenesis. Ratcliff M, Rees D, McGrady S, Buntwal L, Hornsby AKE, Bayliss J, Kent BA, Bussey T, Saksida L, Beynon AL, Howell OW, Morgan AH, Sun Y, Andrews ZB, Wells T, Davies JS. J Neuroendocrinol. 2019 Jun 10:e12755. doi: 10.1111/jne.12755. [Epub ahead of print] PMID: 31179562 Abstract The ageing and degenerating brain show deficits in neural stem/progenitor cell (NSPC) plasticity that are accompanied by impairments in olfactory discrimination. Emerging evidence suggests that the gut-hormone ghrelin plays an important role in protecting neurones, promoting synaptic plasticity and increasing hippocampal neurogenesis in the adult brain. Here, we studied the role of ghrelin in modulating adult sub-ventricular zone (SVZ) NSPCs that give rise to new olfactory bulb (OB) neurones. We characterised the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHSR), using an immuno-histochemical approach in GHSR-eGFP reporter mice to show that GHSR is expressed in several regions, including the OB, but not in the SVZ of the lateral ventricle. These data suggest that acyl-ghrelin does not mediate a direct effect on NSPC in the SVZ. Consistent with these findings, treatment with acyl-ghrelin or genetic silencing of GHSR did not alter NSPC proliferation within the SVZ. Similarly, using a BrdU pulse-chase approach we show that peripheral treatment of adult rats with acyl-ghrelin did not increase the number of new adult-born neurones in the granule cell layer (GCL) of the OB. These data demonstrate that acyl-ghrelin does not increase adult OB neurogenesis. Finally, we studied whether elevating ghrelin indirectly, via calorie restriction (CR), regulated the activity of new adult-born cells in the OB. Overnight CR induced c-Fos expression in new adult-born OB cells, but not in developmentally born cells, whilst neuronal activity was lost following re-feeding. These effects were absent in ghrelin-/- mice, suggesting that adult-born cells are uniquely sensitive to changes in ghrelin mediated by fasting and re-feeding. In summary, ghrelin does not promote neurogenesis in the SVZ and OB, however, new adult-born OB cells are activated by CR in a ghrelin-dependent manner. KEYWORDS: Calorie restriction; Ghrelin; Neurogenesis; Olfactory bulb; Sub-ventricular zone
  12. Intakes of long-chain omega-3 polyunsaturated fatty acids and non-fried fish in relation to incidence of chronic kidney disease in young adults: a 25-year follow-up. Park I, Xun P, Tsinovoi CL, Klemmer P, Liu K, He K. Eur J Nutr. 2019 Jun 7. doi: 10.1007/s00394-019-02022-4. [Epub ahead of print] PMID: 31175412 https://sci-hub.tw/10.1007/s00394-019-02022-4 Abstract PURPOSE: The prevalence of chronic kidney disease (CKD) is increasing rapidly in many countries and has become a major public health concern. Although intakes of long-chain omega-3 polyunsaturated fatty acids (LCω3PUFA) and its food source-fish-may have renal protective effects, little is known about the longitudinal association between these dietary factors and CKD incidence. METHODS: A total of 4133 healthy individuals of black and white race aged 18-30 at baseline (1985-1986) from the Coronary Artery Risk Development in Young Adults study were enrolled and followed up over 25 years. LCω3PUFA and fish intake were assessed by an interview-based dietary history questionnaire at baseline, year 7 (1992-1993) and 20 (2005-2006). RESULTS: Four hundred and eighty-nine incident cases of CKD were identified. After adjustment for potential confounders, LCω3PUFA intake was inversely associated with CKD incidence [HR = 0.73 (95% CI 0.60-0.89), P = 0.002, with one standard division (0.19 g/day) increment in LCω3PUFA]. This inverse association was persisted among females [0.64 (95% CI 0.48, 0.84; P = 0.002], but not males (Pinteraction = 0.070). A marginal significant inverse association was also found between non-fried fish consumption and CKD incidence (HR = 0.86, 95% CI 0.73, 1.01; P = 0.073). CONCLUSIONS: Dietary LCω3PUFA intake was inversely associated with incidence of CKD among American young adults over 25 years of follow-up. The suggestive evidence of the inverse association between non-fried fish consumption with CKD incidence needs further confirmation. KEYWORDS: Chronic kidney disease; Fish; Long-chain omega-3 polyunsaturated fatty acids; Proteinuria A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults. Blanco Mejia S, Messina M, Li SS, Viguiliouk E, Chiavaroli L, Khan TA, Srichaikul K, Mirrahimi A, Sievenpiper JL, Kris-Etherton P, Jenkins DJA. J Nutr. 2019 Jun 1;149(6):968-981. doi: 10.1093/jn/nxz020. PMID: 31006811 Abstract BACKGROUND: Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials. OBJECTIVE: We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein. METHODS: We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified. RESULTS: Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: -6.71, -2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: -9.30, -3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose-response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: -0.77 to -58.60 mg/dL), although only a minority of these were individually statistically significant. CONCLUSIONS: Soy protein significantly reduced LDL cholesterol by approximately 3-4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake. KEYWORDS: LDL cholesterol; cardiovascular disease prevention; lipids; meta-analysis; soy protein; total cholesterol
  13. AlPater

    Al's CR updates

    Analysis of Bone Mineral Profile After Prolonged Every-Other-Day Feeding in C57BL/6J Male and Female Mice. Piotrowska K, Zgutka K, Kupnicka P, Chlubek D, Pawlik A, Baranowska-Bosiacka I. Biol Trace Elem Res. 2019 Jun 8. doi: 10.1007/s12011-019-01758-8. [Epub ahead of print] PMID: 31175634 https://sci-hub.tw/https://link.springer.com/article/10.1007/s12011-019-01758-8 Abstract Intermitted fasting or every-other-day feeding (EOD) has many positive effects in rodents and humans. Our goal was to describe how EOD influences bone mineral composition in female and male mice under prolonged EOD feeding. Male and female adult mice were fed EOD for 9 months. After this time, we used a direct method of measurement of mineral components in ashes of long bones (humerus and radius) to estimate the content of calcium (Ca), phosphorus (P), potassium (K), magnesium (Mg), and sodium (Na). We also performed histological analysis of sections of long bones. We found no significant changes in mineral composition between ad libitum and EOD fed males and females. We noted higher Ca and P contents in control males vs. females and lower content of Mg in control males vs. females. We observed the presence of marrow adipose tissue (MAT) in sections of EOD-fed females. EOD without supplementation during feeding days did not increase loss of mineral content of bones in C57BL/6J mice, but the presence of MAT only in EOD females indicates a gender-dependent response to EOD treatment in C57BL/6J mice. KEYWORDS: Bone mineral profile; Caloric restriction; Every-other-day feeding; Gender difference
  14. Egg Consumption and Risk of Total and Cause-Specific Mortality: An Individual-Based Cohort Study and Pooling Prospective Studies on Behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Mazidi M, Katsiki N, Mikhailidis DP, Pencina MJ, Banach M. J Am Coll Nutr. 2019 Jun 7:1-12. doi: 10.1080/07315724.2018.1534620. [Epub ahead of print] PMID: 31173548 https://sci-hub.tw/10.1080/07315724.2018.1534620 Abstract The associations of egg consumption with total, coronary heart disease (CHD), and stroke mortality are poorly understood. We prospectively evaluated the link between total, CHD, and stroke mortality with egg consumption using a randomly selected sample of U.S. adults. Next we validated these results within a meta-analysis and systematic review of all available prospective results. We assessed the mean of cardiometabolic risk factors across the intake of eggs. We made the analysis based on data from the National Health and Nutrition Examination Surveys (NHANES; 1999-2010). In NHANES, vital status through December 31, 2011, was ascertained. Cox proportional hazard regression models were used to relate baseline egg consumption with all-cause and cause-specific mortality. PubMed, Scopus, Web of Science, and Google Scholar databases were also searched (up to December 2017). The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. Overall, 23,524 participants from NHANES were included (mean age of 47.7 years; 48.7% were men). Across increasing the intake of eggs, adjusted mean levels of cardiometabolic risk factors worsened. Adjusted logistic regression showed that participants in the highest category of egg intake had a greater risk of diabetes (T2DM; 30%) and hypertension (HTN; 48%). With regard to total and CHD mortality, multivariable Cox regression in a fully adjusted model showed no link in males and females. In males, egg intake had a reverse (66%) association with stroke mortality, while this link was not significant among females. The results of pooling data from published prospective studies also showed no link between CHD and total mortality with egg consumption, whereas we observed a reverse (28%) association between egg intake and stroke mortality. These findings were robust after sensitivity analysis. According to our findings, egg intake had no association with CHD and total mortality, whereas was associated with lower risk of mortality from stroke. Egg consumption was associated with T2DM, HTN, C-reactive protein, and markers of glucose/insulin homeostasis. If confirmed in clinical trials (causation), this information may have applications for population-wide health measures. Key teaching points No link between total and CHD mortality with eggs intake in males and females. In males, egg intake had a reverse association with stroke mortality, while this link was not significant among females. The results of pooling data from published prospective studies also showed no link between CHD and total mortality with egg consumption, whereas we observed a reverse association between egg intake and stroke mortality. KEYWORDS: Egg; coronary heart disease; diabetes; hypertension; mortality; stroke Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease. Okada Y, Uehara S, Shibata M, Koh H, Oue K, Kambe H, Morimoto M, Sato KK, Hayashi T. Am J Nephrol. 2019 Jun 6:1-8. doi: 10.1159/000500707. [Epub ahead of print] PMID: 31170706 Abstract BACKGROUND: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. METHODS: A prospective cohort study of 9,116 middle-aged nondiabetic -Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1-23.0 g ethanol/day), moderate drinkers (23.1-46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. RESULTS: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11-1.70), 1.58 (95% CI 1.28-1.95), 2.27 (95% CI 1.86-2.77), and 3.12 (95% CI 2.56-3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46-0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. CONCLUSIONS: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD. KEYWORDS: Alcohol; Chronic kidney disease; Estimated glomerular filtration rate; Prospective cohort study; Uric acid Prospective investigation of serum metabolites, coffee drinking, liver cancer incidence, and liver disease mortality. Loftfield E, Rothwell JA, Sinha R, Keski-Rahkonen P, Robinot N, Albanes D, Weinstein SJ, Derkach A, Sampson J, Scalbert A, Freedman ND. J Natl Cancer Inst. 2019 Jun 5. pii: djz122. doi: 10.1093/jnci/djz122. [Epub ahead of print] PMID: 31168595 Abstract BACKGROUND: Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development. METHODS: We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the ATBC cohort (N = 29,133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes. RESULTS: Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% CI = 2.00-7.74) for tyrosine to 4.95 (95% CI = 2.64-9.29) for GCA and from 4.00 (95% CI = 2.42-6.62) for GCA to 6.77 (95% CI = 3.62-12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; ORs ranged from 0.16 to 0.37. Associations persisted following diet-adjustment and for outcomes occurring >10 years after blood collection. CONCLUSIONS: A broad range of compounds were associated with coffee drinking, incident liver cancer and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee. KEYWORDS: bile acids; cirrhosis; coffee; hepatocellular carcinoma; metabolomics Towards a unified mechanistic theory of aging. Barja G. Exp Gerontol. 2019 Jun 4. pii: S0531-5565(19)30173-1. doi: 10.1016/j.exger.2019.05.016. [Epub ahead of print] Review. PMID: 31173843 Abstract A large amount of the longevity-modulating genes discovered during the last two decades are highly conserved during evolution from yeast and invertebrates to mammals. Many different kinds of evidence converge in the concept that life extending manipulations like the dietary restrictions or rapamycin signal the nucleus specifically changing gene expression to increase longevity. The response of the cell aging regulation system is to change the level of activity of many different aging effectors to modulate longevity. Aging effectors include mitROS production, lipid unsaturation, autophagy, mitochondrial DNA repair and possibly others like apoptosis, proteostasis, or telomere shortening, corresponding to different classic theories of aging. The constitutive spontaneous activity of this aging regulating system, likely including epigenetics, can also explain species longevity. The aging regulating system reconciles the previously considered independent theories of aging bringing them together into a single unified theory of aging. KEYWORDS: Aging; Autophagy; Free radicals; Longevity; Reactive oxygen species production Carbohydrate-Rich Diet Is Associated with Increased Risk of Incident Chronic Kidney Disease in Non-Diabetic Subjects. Nam KH, An SY, Joo YS, Lee S, Yun HR, Jhee JH, Han SH, Yoo TH, Kang SW, Park JT. J Clin Med. 2019 Jun 4;8(6). pii: E793. doi: 10.3390/jcm8060793. PMID: 31167515 Abstract Despite the potential relationship with metabolic derangements, the association between dietary carbohydrate intake and renal function remains unknown. The present study investigated the impact of dietary carbohydrate intake on the development of incident chronic kidney disease (CKD) in a large-scale prospective cohort with normal renal function. A total of 6746 and 1058 subjects without and with diabetes mellitus (DM) were analyzed, respectively. Carbohydrate intake was assessed by a 24-h dietary recall food frequency questionnaire. The primary endpoint was CKD development, defined as a composite of estimated glomerular filtration rate (eGFR) of ≤60 mL/min/1.73 m2 and the development of proteinuria. CKD newly developed in 20.1% and 36.0% of subjects during median follow-ups of 140 and 119 months in the non-DM and DM subjects, respectively. Categorization of non-DM subjects into dietary carbohydrate density quartiles revealed a significantly higher risk of CKD development in the third and fourth quartiles than in the first quartile (P = 0.037 for first vs. third; P = 0.001 for first vs. fourth). A significant risk elevation was also found with increased carbohydrate density when carbohydrate density was treated as a continuous variable (P = 0.008). However, there was no significant difference in the incident CKD risk among those with DM according to dietary carbohydrate density quartiles. Carbohydrate-rich diets may increase the risk of CKD development in non-DM subjects. KEYWORDS: carbohydrate density; chronic kidney disease; dietary carbohydrate; renal nutrition Prospective Association of Serum and Dietary Magnesium with Colorectal Cancer Incidence. Polter E, Onyeaghala GC, Lutsey PL, Folsom AR, Joshu CE, Platz EA, Prizment AE. Cancer Epidemiol Biomarkers Prev. 2019 Jun 5. pii: cebp.1300.2018. doi: 10.1158/1055-9965.EPI-18-1300. [Epub ahead of print] PMID: 31167754 Abstract BACKGROUND: Laboratory and epidemiological research suggests a protective role of magnesium in colorectal cancer development. We estimated the associations of serum and dietary magnesium with colorectal cancer incidence in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Serum magnesium concentration was measured in blood collected twice (1987-1989 and 1990-1992) and averaged. Dietary magnesium was assessed by food-frequency questionnaire administered twice (1987-1989 and 1993-1995) and averaged. For both dietary and serum magnesium, the averaged measures were categorized into quintiles for analysis. Analyses included 315 colorectal cancer cases among 13,009 participants for serum magnesium (followed for a median of 20.4 years), and 256 cases among 10,971 participants for dietary magnesium (followed for a median of 17.5 years). Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Multivariable-adjusted HRs (95% CI) of colorectal cancer for the highest four quintiles compared to the first quintile of serum magnesium were: Q2: 0.70 (0.49-0.99); Q3: 0.68 (0.47-1.00) Q4: 0.87 (0.62-1.21); and Q5: 0.79 (0.57-1.11; p-trend=0.04). An inverse association was present in females (HR for Q5 vs Q1: 0.59, 95% CI: 0.36-0.98, p-trend=0.01), but not males (HR for Q5 vs Q1: 1.10, 95% CI: 0.67-1.79, p-trend=0.92; p-interaction=0.34). Dietary magnesium was not statistically significantly associated with colorectal cancer risk. CONCLUSIONS: Our study found a higher risk of colorectal cancer with lower serum magnesium among females, but not males. IMPACT: If our findings are confirmed, maintaining adequate serum magnesium levels may be important for colorectal cancer prevention. Effects of aspirin and non-steroidal anti-inflammatory drugs on the risk of cholangiocarcinoma: a meta-analysis. Lapumnuaypol K, Tiu A, Thongprayoon C, Wijarnpreecha K, Ungprasert P, Mao MA, Cheungpasitporn W. QJM. 2019 Jun 1;112(6):421-427. doi: 10.1093/qjmed/hcz039. PMID: 30753687 Abstract BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the proliferation of cholangiocarcinoma (CCA) cells in vitro through inhibition of cyclooxygenase-2. However, the effects of aspirin and NSAIDs on the risk of CCA remain unclear. We performed this meta-analysis to assess the risk of biliary tract cancers in patients who take aspirin and/or NSAIDs. METHODS: A systematic review was conducted utilizing MEDLINE, EMBASE, Cochrane databases from inception through October 2017 to identify studies that assessed the association of aspirin and/or NSAIDs use with risk of biliary tract cancers including CCA, gallbladder cancer and ampulla of Vater cancer. Effect estimates from the studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Five observational studies with a total of 9 200 653 patients were enrolled. The pooled OR of CCA in patients with aspirin use was 0.56 (95% CI, 0.32-0.96). Egger's regression asymmetry test was performed and showed no publication bias for the association between aspirin use and CCA with P = 0.42. There was no significant association between NSAIDs use and CCA, with a pooled OR of 0.79 (95% CI, 0.28-2.21). One study showed a significant association between aspirin use and reduced risk of gallbladder cancer with OR of 0.37 (0.17-0.80). However, there was no significant association between aspirin and ampulla of Vater cancer with OR of 0.22 (0.03-1.65). CONCLUSIONS: Our study demonstrates a significant association between aspirin use and a 0.56-fold decreased risk of CCA. However, there is no association between the use of NSAIDs and CCA.
  15. AlPater

    Al's CR updates

    Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa. Iwamura H, Kondo K, Kikuta S, Nishijima H, Kagoya R, Suzukawa K, Ando M, Fujimoto C, Toma-Hirano M, Yamasoba T. Cell Tissue Res. 2019 Jun 6. doi: 10.1007/s00441-019-03047-1. [Epub ahead of print] PMID: 31168693 Abstract The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured. KEYWORDS: Caloric restriction; Cell proliferation; DNA microarray; Interleukin-6; Olfactory neuroepithelium A Nutrition-Longevity Tradeoff Enforced by Innate Immunity. Wani KA, Goswamy D, Irazoqui JE. Mol Cell. 2019 Jun 6;74(5):864-865. doi: 10.1016/j.molcel.2019.05.012. PMID: 31173721 Abstract Dietary restriction (DR) extends lifespan in multiple animal species, but the underlying molecular mechanisms remain poorly understood. A recent study published in Cell Metabolism by Wu et al. (2019) shows that DR represses an evolutionarily conserved p38 MAPK pathway involved in innate immunity, leading to diminished expression of p38 MAPK-regulated genes and extended lifespan. >>>>>>>>>>>>>>>>>>> Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity. Wu Z, Isik M, Moroz N, Steinbaugh MJ, Zhang P, Blackwell TK. Cell Metab. 2019 Mar 5. pii: S1550-4131(19)30102-0. doi: 10.1016/j.cmet.2019.02.013. [Epub ahead of print] PMID: 30905669 https://sci-hub.tw/10.1016/j.cmet.2019.02.013