Pre- and post-diagnosis body mass index and heart failure mortality: a dose-response meta-analysis of observational studies reveals greater risk of being underweight than being overweight.

OBJECTIVE: To investigate the dose-response association between pre- and post-diagnosis body mass index (BMI) and heart failure (HF) mortality. METHODS: Eligible observational studies were searched in databases, up to November 2017. We used random-effects generalized least squares spline models for trend estimation to derive pooled BMI unit-HF mortality relationship. RESULTS: Sixteen cohort studies (six pre-diagnosis and 10 post-diagnosis BMI) were included, comprising a total of 258,379 subjects with 13,201 deaths due to HF. A nonlinear U-shaped association was found between pre-diagnosis BMI and the risk of HF mortality, with a greater risk from being at the lowest extreme, rather than being at the top category. The combined hazard ratio of HF mortality among the highest compared to the lowest category of pre-diagnosis BMI was 1.24 (0.65-2.37, I2  = 90.7%). No significant nonlinear association was found between post-diagnosis BMI and HF mortality as well as when comparing the highest to the lowest category of BMI. CONCLUSIONS: This meta-analysis showed those with both high and low pre-diagnosis BMI had higher risk for HF mortality, with a greater risk from being too underweight, rather than being obese. No significant association was found between post-diagnosis BMI and the risk of HF mortality. Further detailed investigations are needed to accurately examine the potential mechanistic links between BMI and health outcomes.

Dietary fat, saturated fatty acid, and monounsaturated fatty acid intakes and risk of bone fracture: a systematic review and meta-analysis of observational studies.

Total dietary fat intake might influence the risk of fracture; however, conflicting findings have been reported to date. Moreover, the type of fatty acids is also of vital importance. We aimed to conduct a comprehensive review of the literature on the association between dietary fat intake, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and the risk of fracture. PubMed and Scopus were used to conduct a comprehensive search for articles published up to 7 January 2018. To pool effect sizes, random effects models (the DerSimonian-Laird method) were applied. The Cochrane Q test was used to trace the source of between-study heterogeneity. Six studies met inclusion criteria for meta-analysis. We found no significant association between total dietary fat intake and risk of fracture (pooled effect size 1.31, 95% confidence interval (95% CI) 0.95-1.79, P = 0.09). A significant positive association was observed between SFA intake and the risk of hip fracture (pooled effect size 1.79, 95% CI 1.05-3.03, P = 0.03). There was also a significant positive association between MUFAs derived from animal sources and the risk of fracture (pooled effect size 2.29, 95% CI 1.50-3.50, P < 0.0001). Our findings showed a strong positive association between SFAs intake and risk of hip fracture. Moreover, there was a significant positive association between MUFAs derived from animal sources and the risk of fracture.

Body mass index, abdominal adiposity, weight gain and risk of developing hypertension: a systematic review and dose-response meta-analysis of more than 2.3 million participants.

OBJECTIVE: This study aimed to test the association between anthropometric measures and risk of developing hypertension. METHODS: We did a systematic search using PubMed and Scopus, from inception up to January 2017. Prospective cohort studies reporting the risk estimates of hypertension for three or more quantitative categories of indices of general and abdominal adiposity were included. Summary relative risks were calculated using random-effects models. RESULTS: Fifty-seven prospective cohort studies were included. Summary relative risks were 1.49 (95% confidence interval [CI]: 1.41, 1.58; I2  = 97.4%, n = 50) for a five-unit increment in body mass index, 1.27 (95%CI: 1.15, 1.39; I2  = 95.0%, n = 14) for a 10-cm increment in waist circumference, 1.16 (95%CI: 1.09, 1.23; I2  = 77.8%, n = 5) for weight gain equal to a one-unit increment in BMI, and 1.37 (95%CI: 1.24, 1.51; I2  = 76.4%, n = 8) and 1.74 (95%CI: 1.35, 2.13; I2  = 58.9%, n = 4) for a 0.1-unit increment in waist-to-hip ratio and waist-to-height ratio, respectively. The risk of hypertension increased continuously with increasing all anthropometric measures, and also along with weight gain. CONCLUSION: Being as lean as possible within the normal body mass index range may be the best suggestion in relation to primary prevention of hypertension.

Fasting blood glucose and risk of prostate cancer: A systematic review and meta-analysis of dose-response.

AIM: This study aimed to test the dose-response relationship between fasting blood glucose (FBG) levels and risk of prostate cancer. METHODS: A systematic search was done of PubMed and Scopus from their inception up to January 2017. Prospective and retrospective studies reporting risk estimates of prostate cancer for two or more categories of blood glucose levels were identified, and two independent authors extracted the information. Relative risk (RR) was calculated using random-effects models and pooled. RESULTS: Ten prospective cohort studies, one nested case-control study, one case-cohort study and three case-control studies (total n=1,214,947) involving 12,494 cases of prostate cancer were reviewed. The pooled RR of prostate cancer for the highest vs. lowest category of FBG was 0.88 (95% CI: 0.78-0.98, I2=25.5%, n=15 studies). A 10mg/dL increment in FBG level was not associated with risk of prostate cancer (0.98, 95% CI: 0.96-1.00, I2=45.4%, n=11 studies). Subgroup analyses yielded a significant inverse association only in the subgroup of cohort studies. Non-linear dose-response meta-analysis showed a very slight decrement in risk with increasing FBG levels. Sensitivity analyses using cohort studies showed a steep decrease in risk along with an increase in FBG from baseline levels of ≈70mg/dL across prediabetes and diabetes ranges. CONCLUSION: Higher FBG levels are associated with lower risk of prostate cancer in cohort studies, but not in case-control studies, findings that limit interpretation of our present results.

Vitamin D and serum leptin: a systematic review and meta-analysis of observational studies and randomized controlled trials.

We aimed to investigate the potential association between vitamin D and serum leptin levels by pooling together the results from observational studies and clinical trials. A systematic literature search of PubMed, Scopus and Google Scholar was conducted up to March 2015. The analysis of observational studies was conducted on six papers that reported nine correlation coefficients using Fisher's Z and its standard error. Then, effect sizes of eligible trials were pooled using random-effects models (the DerSimonian-Laird estimator). Results of observational studies showed an inverse association between leptin and 25-hydroxyvitamin D (25(OH)D) (Fisher's Z=-0.93, 95% CI: -0.95, -0.91). After combining trials, pooled mean difference (PMD) for 25(OH)D was 24.06 ng/ml (95% CI, 17.27-30.85; P<0.001) with significant heterogeneity among studies (P<0.001; I2=89.1%). Raising 25(OH)D was associated with significant increase in leptin level (PMD=4.60 ng/ml, 95% CI, 0.55-8.66, P=0.026) with significant heterogeneity (P<0.001; I2=96.4%). Population with diabetes (PMD: 13.63 ng/ml), age younger than 50 years (PMD: 1.884 ng/ml), doses less than 1000 IU/day (PMD: 1.53 ng/ml), duration less than 24 weeks (PMD: 14.668 ng/ml) and baseline 25(OH)D <50 nmol/l (PMD: 13.483 ng/ml) were sources of heterogeneity. Current evidence indicates that inverse association between leptin level and 25(OH)D concentration was observed in observational studies, which was not demonstrated in intervention studies with high heterogeneity. Clearly, there is a need for properly designed and large prospective dose-response trials with long-term follow-up to assess the sources of heterogeneity.

Effect of vitamin D3 supplementation on blood pressure in adults: An updated meta-analysis.

BACKGROUND AND AIMS: Previous randomized clinical trials (RCTs) of the effects of vitamin D3 supplementation (VD3S) on blood pressure have generated inconsistent results. We evaluated the effect of VD3S on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a meta-analysis. DATA SYNTHESIS: Literature searches of PubMed, Scopus, Ovid, and Google scholar for publications in English were conducted up to April 2015. RCTs that assessed the effect of VD3S on SBP and DBP were selected. CONCLUSIONS: A total of 30 RCTs with 41 arms including 4744 participants were included. The mean duration of the studies was 5.6 ± 4.0 months, and doses of VD3S varied between 200 and 12,000 IU/day. VD3S had no effect on SBP (-0.68 mmHg, 95%CI: -2.19 to 0.84), and DBP (-0.57 mmHg, 95%CI: -1.36 to 0.22). Subgroup analysis revealed that daily vitamin D3 therapy at a dose of >800 IU/day for <6 months in subjects ≥50 years old reduced both SBP and DBP (p < 0.001). In addition, VD3S showed hypotensive effects in healthy subjects and hypertensive patients, but a hypertensive effect in overweight and obese subjects. However, after excluding overweight and obese subjects, VD3S significantly reduced SBP and DBP. VD3S in combination with calcium supplementation significantly elevated SBP (3.64 mmHg, 95%CI: 3.15-4.13) and DBP (1.71 mmHg, 95%CI: 1.25-2.18). No evidence of publication bias was found. The effects of VD3S on blood pressure depend on dose of supplementation, treatment regimens, trial duration, and population subgroup. Supplementation may be beneficial at daily doses >800 IU/day for <6 months in subjects ≥50 years old.

The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials.

This study provides a systematic review and meta-analysis of randomized controlled trials, which have examined the effect of the carnitine on adult weight loss. Relevant studies were identified by systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials and reference lists of relevant marker studies. Nine studies (total n = 911) of adequate methodological quality were included in the review. Trials with mean difference (MD) of 95% confidence interval (CI) were pooled using random effect model. Results from meta-analysis of eligible trials revealed that subjects who received carnitine lost significantly more weight (MD: -1.33 kg; 95% CI: -2.09 to -0.57) and showed a decrease in body mass index (MD: -0.47 kg m(-2) ; 95% CI: -0.88 to -0.05) compared with the control group. The results of meta-regression analysis of duration of consumption revealed that the magnitude of weight loss resulted by carnitine supplementation significantly decreased over time (p = 0.002). We conclude that receiving the carnitine resulted in weight loss. Using multiple-treatments meta-analysis of the drugs and non-pharmacotherapy options seem to be insightful areas for research. © 2016 World Obesity.

The effects of weight loss approaches on bone mineral density in adults: a systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: We assessed the impact of weight loss strategies including calorie restriction and exercise training on BMD in adults using a systematic review of randomized controlled trials. Weight reduction results in reduced BMD at the hip, but has less effect on the spine. Both calorie restriction and a combination of calorie restriction and exercise result in a decrease in hip bone density, whereas weight loss response to exercise training without dietary restriction leads to increased hip BMD. INTRODUCTION: Findings are not consistent on the effect of weight loss on bone mineral density (BMD). We conducted a systematic review on the randomized controlled trials to assess the effect of weight loss strategies, including calorie restriction and exercise programs on BMD in adults. METHODS: A structured and comprehensive search of MEDLINE and EMBASE databases was undertaken up to March 2016. Study-specific mean differences (MD) were pooled using a random-effects model. Subgroup analysis and meta-regression were used to find possible sources of between-study heterogeneity. RESULTS: Thirty-two randomized controlled trials met predetermined inclusion criteria. The meta-analysis revealed no significant difference on total BMD (MD 0.007, 95 % CI -0.020-0.034, p = 0.608). In contrast, the pooled data of studies showed a significant effect of weight loss on hip BMD (MD -0.008, 95 % CI -0.09 to -0.006 g/cm(2), p < 0.001) and also lumbar spine BMD (MD -0.018 g/cm(2), 95 % CI -0.019 to -0.017, p < 0.001). BMD in the hip site decreased after more than 4 months, especially in those who were obese. Moreover, calorie restriction interventions longer than 13 months showed a significant decreased in lumbar spine BMD. CONCLUSION: Weight loss led to significant decreases at the hip and lumbar spine BMD but not at the total. Weight loss response following calorie restriction resulted in a decrease in hip and lumbar spine bone density especially more than 1 year; whereas an exercise-induced weight loss did not.

Effect of vitamin E supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials.

C-reactive protein (CRP), a marker of chronic inflammation, has a major role in the etiology of chronic disease. Vitamin E may have anti-inflammatory effects. However, there is no consensus on the effects of vitamin E supplementation on CRP levels in clinical trials. The aim of this study was to systematically review randomized controlled trials (RCTs) that report on the effects of vitamin E supplementation (α- and γ-tocopherols) on CRP levels. A systematic search of RCTs was conducted on Medline and EMBASE through PubMed, Scopus, Ovid and Science Direct, and completed by a manual review of the literature up to May 2014. Pooled effects were estimated by using random-effects models and heterogeneity was assessed by Cochran's Q and I(2) tests. Subgroup analyses and meta-regression analyses were also performed according to intervention duration, dose of supplementation and baseline level of CRP. Of 4734 potentially relevant studies, only 12 trials met the inclusion criteria with 246 participants in the intervention arms and 249 participants in control arms. Pooled analysis showed a significant reduction in CRP levels of 0.62 mg/l (95% confidence interval = -0.92, -0.31; P < 0.001) in vitamin E-treated individuals, with the evidence of heterogeneity across studies. This significant effect was maintained in all subgroups, although the univariate meta-regression analysis showed that the vitamin E supplementation dose, baseline level of CRP and duration of intervention were not the sources of the observed heterogeneity. The results of this meta-analysis suggest that supplementation with vitamin E in the form of either α-tocopherol or γ-tocopherol would reduce serum CRP levels.

The interactive effect of improvement of vitamin D status and VDR FokI variants on oxidative stress in type 2 diabetic subjects: a randomized controlled trial.

BACKGROUND/OBJECTIVES: The objectives were to evaluate the effects of improvement of vitamin D status on biomarkers of oxidative stress (OS) in type 2 diabetic (T2D) subjects and whether vitamin D receptor (VDR)-FokI polymorphisms could modulate the response to vitamin D3 intake. SUBJECTS/METHODS: Subjects with T2D were allocated to one of the two groups to receive either plain doogh (PD; containing 150 mg calcium and no vitamin D/250 ml, n1=50) or vitamin D3-fortified doogh (FD; containing 500 IU/250 ml, n1=50) twice a day for 12 weeks. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH)D), superoxide dismutase, glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA). VDR genotypes in 140 T2D subjects in FD were determined by FokI restriction enzyme. RESULTS: After 12 weeks, serum 25(OH)D increased significantly in FD (from 38.5±202.2 to 72.0±23.5, P<0.001) as compared with PD (from 38.8±22.8 to 33.4±22.8, P=0.28). Comparisons between FD and PD revealed significant differences in changes of serum MDA (-0.54±0.82 µmol/l vs. +0.17±1 µmol/l, P<0.001), GSH (+8.4±40.1 ng/l vs -13.1±29.4 ng/l, P=0.002) and TAC (+0.14±0.43 mmol/l vs. +0.02±0.45 mmol/l bovine serum albumin equivalent, P=0.03). Although there was no significant association between FokI genotypes and OS biomarkers, ff variant subgroup showed the weakest response to vitamin D. CONCLUSIONS: Improvement of vitamin D status via daily intake of FD ameliorates OS biomarkers in T2D subjects and the interactive effect of FokI genotypes cannot be ruled out.

Metabolic syndrome profiles, obesity measures and intake of dietary fatty acids in adults: Tehran Lipid and Glucose Study.

BACKGROUND: To determine the association between fatty acid intake and the prevalence of risk factors for the metabolic syndrome. METHODS: In this population-based cross-sectional study, a sample of 2750 Tehranian subjects (44% men and 56% women) aged 20-74 years, who completed a validated food frequency questionnaire, was studied. The metabolic syndrome (MetS) was defined in accordance with the modified guidelines of the National Cholesterol Education Program Adults Treatment Panel III, and waist circumference was coded according to the newly-introduced cut-off points for Iranian adults (≥95 cm for both sexes). Metabolic risk factors across quartile categories of each type of dietary fat [total fat intake, total poly-unsaturated fatty acid (PUFA) intake, total MUFA intake, total saturated fatty acid (SFA) intake expressed as percentage of energy and quartiles of the ratio of polyunsaturated fat to saturated fat (P : S)] were compared. RESULTS: The mean (SD) ages of participants were 40.8 (14.6) and 38.6 (12.9) years, respectively, for men and women. The mean contribution of fat to energy intake was approximately 26% in men and women. A positive trend over successive quartiles of SFA intake with low-density lipoprotein-cholesterol (LDL-C) and triglyceride, as well as P/S ratio intake with high-density lipoprotein-cholesterol (HDL-C), was found. An inverse association between HDL-C with SFA and PUFA intake and a positive association with MUFA and the P/S ratio was found. A significant association of fatty acid consumption and risk of the MetS in this population was observed, except for total PUFA intake. CONCLUSIONS: Special dietary fatty acids are associated with metabolic risk factors among the Iranian population. Because of the high prevalence of cardiovascular disease and MetS, national nutrition policies must be developed accordingly for the modification of dietary fatty acid intake with respect to causation and prevention.