Vitamin D supplementation for preventing infections in children under five years of age.

BACKGROUND: Vitamin D is a micronutrient important for bone growth and immune function. Deficiency can lead to rickets and has been linked to various infections, including respiratory infections. The evidence on the effects of supplementation on infections in children has not been assessed systematically. OBJECTIVES: To evaluate the role of vitamin D supplementation in preventing pneumonia, tuberculosis (TB), diarrhoea, and malaria in children under five years of age. This includes high-, middle-, and low-income countries. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, MEDLINE, EMBASE, LILACS, the WHO International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) , ClinicalTrials.gov and the ISRCTN registry (http://www.isrctn.com/) up to 16 June 2016. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated preventive supplementation of vitamin D (versus placebo or no intervention) in children under five years of age. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts, extracted the data, and assessed the risk of bias of included trials. MAIN RESULTS: Four trials met the inclusion criteria, with a total of 3198 children under five years of age, and were conducted in Afghanistan, Spain, and the USA. Prevalence of vitamin D deficiency varied widely in these populations (range: 73.1% in Afghanistan, 10 to 12% in USA, and 6.2% in Spain). The included trials evaluated mortality (two trials), pneumonia incidence (two trials), diarrhoea incidence (two trials), hospitalization (two trials), and mean serum vitamin D concentrations (four trials).We do not know whether vitamin D supplementation impacts on all-cause mortality because this outcome was underpowered due to few events (risk ratio (RR) 1.43, 95% confidence interval (CI) 0.54 to 3.74; one trial, 3046 participants, low quality evidence).For pneumonia, episodes of 'radiologically confirmed' first or only episode of pneumonia were little different in the supplemented and unsupplemented group (Rate Ratio: 1.06, 95% confidence interval (CI) 0.89 to 1.26; two trials, 3134 participants, moderate quality evidence), and similarly for children with confirmed or unconfirmed pneumonia (RR 0.95, 95% CI 0.87 to 1.04; one trial, 3046 participants). In these two trials there were no obvious differences between supplemented and unsupplemented children regarding episodes of diarrhoea.In the single large trial from Afghanistan, the trial authors reported that vitamin D supplementation was associated with an increase in repeat episodes of pneumonia confirmed by chest radiograph (RR 1.69, 95% CI 1.28 to 2.21; one trial, 3046 participants), but not reflected in the outcome of confirmed or unconfirmed pneumonia (RR 1.06, 95% CI 1.00 to 1.13; one trial, 3046 participants).For hospital admission measured in one small trial, there was no difference detected (RR 0.86, 95% CI 0.20 to 3.62; one trial, 88 participants; very low quality evidence).The mean serum vitamin D concentrations were higher in supplemented compared to unsupplemented children at the end of supplementation (MD 7.72 ng/mL, 95% CI 0.50 to 14.93; four trials, 266 participants, low quality evidence). These results were driven primarily by two smaller trials with large magnitudes of effect. In the other two bigger trials, serum vitamin D concentrations were elevated in the intervention group for most of the trial duration but not at the end of supplementation. This may be due to time elapsed at measurement from the last dose, incomplete compliance, or increased need of vitamin D with infant age.We did not find any trial that reported on the incidence of TB, malaria or febrile illness, duration of pneumonia, duration of diarrhoea, severity of infection, and cause-specific mortality (due to TB, diarrhoea, or malaria). AUTHORS' CONCLUSIONS: Evidence from one large trial did not demonstrate benefit of vitamin D supplementation on the incidence of pneumonia or diarrhoea in children under five years. To our knowledge, trials that evaluated supplementation for preventing other infections, including TB and malaria, have not been performed.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

IMPORTANCE: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts.

BACKGROUND: In prospective studies, the relationship of self-reported consumption of dairy foods with risk of diabetes mellitus is inconsistent. Few studies have assessed dairy fat, using circulating biomarkers, and incident diabetes mellitus. We tested the hypothesis that circulating fatty acid biomarkers of dairy fat, 15:0, 17:0, and t-16:1n-7, are associated with lower incident diabetes mellitus. METHODS AND RESULTS: Among 3333 adults aged 30 to 75 years and free of prevalent diabetes mellitus at baseline, total plasma and erythrocyte fatty acids were measured in blood collected in 1989 to 1990 (Nurses' Health Study) and 1993 to 1994 (Health Professionals Follow-Up Study). Incident diabetes mellitus through 2010 was confirmed by a validated supplementary questionnaire based on symptoms, diagnostic tests, and medications. Risk was assessed by using Cox proportional hazards, with cohort findings combined by meta-analysis. During mean±standard deviation follow-up of 15.2±5.6 years, 277 new cases of diabetes mellitus were diagnosed. In pooled multivariate analyses adjusting for demographics, metabolic risk factors, lifestyle, diet, and other circulating fatty acids, individuals with higher plasma 15:0 had a 44% lower risk of diabetes mellitus (quartiles 4 versus 1, hazard ratio, 0.56; 95% confidence interval, 0.37-0.86; P-trend=0.01); higher plasma 17:0, 43% lower risk (hazard ratio, 0.57; 95% confidence interval, 0.39-0.83; P-trend=0.01); and higher t-16:1n-7, 52% lower risk (hazard ratio, 0.48; 95% confidence interval, 0.33-0.70; P-trend <0.001). Findings were similar for erythrocyte 15:0, 17:0, and t-16:1n-7, although with broader confidence intervals that only achieved statistical significance for 17:0. CONCLUSIONS: In 2 prospective cohorts, higher plasma dairy fatty acid concentrations were associated with lower incident diabetes mellitus. Results were similar for erythrocyte 17:0. Our findings highlight the need to better understand the potential health effects of dairy fat, and the dietary and metabolic determinants of these fatty acids.