The effect of vitamin D3 supplementation on atrial fibrillation in generally healthy men and women: The Finnish Vitamin D Trial.

Atrial fibrillation is a common cardiac arrhythmia with high morbidity risk. Observational studies suggest that vitamin D deficiency is associated with higher atrial fibrillation risk but there is limited evidence whether vitamin D supplementation could affect the risk. In these post hoc analyses from the Finnish Vitamin D Trial, we compared the incidence of atrial fibrillation with 5-year supplementation of vitamin D3 (1600 IU/d or 3200 IU/d) vs placebo. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.

Efficacy of vitamin D3 supplementation on cancer mortality: Systematic review and individual patient data meta-analysis of randomised controlled trials.

To evaluate the effect of vitamin D3 supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and meta-analysis of randomised, placebo-controlled trials (RCTs) and individual patient data (IPD) was conducted. Overall, 14 RCTs with a total of 104,727 participants (2015 cancer deaths) were identified and 7 RCTs, including 90 % of all study participants (n = 94,068), could be included in the IPD meta-analyses. The main meta-analysis of the 14 RCTs yielded a statistically non-significant reduction in cancer mortality by 6 % (risk ratio (RR) [95%-confidence interval (95%CI)]: 0.94 [0.86-1.02]). Subgroup analyses revealed a 12 % lower cancer mortality in the vitamin D3 group compared with the placebo group in 10 trials with a daily dosing regimen (RR [95%CI]: 0.88 [0.78-0.98]), whereas no mortality reduction was seen in 4 trials using a bolus regimen (RR [95%CI]: 1.07 [0.91-1.24]; p-value for interaction: 0.042). The IPD meta-analysis (RR [95%CI]: 0.93 [0.84; 1.02]) confirmed the finding of all trials. The IPD were used to test effect modification by age, sex, body mass index, ethnicity, baseline serum 25-hydroxyvitamin D concentration, adherence and cancer-related factors but no statistically significant findings were obtained in meta-analyses of all trials. When restricted to trials with daily dosing in a post-hoc analysis, adults aged ≥ 70 years (RR [95%CI]: 0.83 [0.77; 0.98]) and subjects with vitamin D3 therapy initiation before cancer diagnosis (RR [95%CI]: 0.87 [0.69; 0.99]) appeared to benefit most from daily vitamin D3 supplementation. Measurements of baseline 25-hydroxyvitamin D levels and inclusion of other than non-Hispanic White adults were too sparse in the trials to draw conclusions. Results for all-cause and cancer-specific survival of participants with cancer were comparable to those obtained in the general population for cancer mortality. In conclusion, vitamin D3 did not reduce cancer mortality in the main meta-analysis of all RCTs because the observed risk reduction by 6 % was not statistically significant. However, a subgroup analysis revealed that vitamin D3 administered daily, in contrast to bolus supplementation, reduced cancer mortality by 12 %.

Associations of serum n-3 and n-6 polyunsaturated fatty acids with prevalence and incidence of nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver diseases worldwide, and lifestyle and diet are significant factors in its development. Recent studies have suggested that dietary fat quality is associated with the development of NAFLD. OBJECTIVES: Our purpose was to investigate the cross-sectional and longitudinal associations of serum n-3 (ω-3) and n-6 (ω-6) PUFAs with NAFLD among middle-aged and older men and women from eastern Finland. We also investigated the associations of estimated Δ5-desaturase and Δ6-desaturase activities, enzymes involved in PUFA metabolism, with NAFLD. METHODS: After exclusions, the cross-sectional analyses included 1533 men examined in 1984-1989 and 674 men and 870 women examined in 1998-2001 in the Kuopio Ischaemic Heart Disease Risk Factor Study. The longitudinal analyses included 520 men examined in 1991-1993 and 301 men and 466 women examined in 2005-2008. Fatty liver index (FLI) was used as a surrogate for NAFLD. Hepatic steatosis was defined as FLI >60. ANCOVA and logistic regression were used for analyses. RESULTS: In the longitudinal analyses, participants with higher serum concentrations of total n-6 PUFA and linoleic acid, the major n-6 PUFA, had markedly lower FLI and lower odds for hepatic steatosis (e.g., odds ratios for incident hepatic steatosis in the highest compared with lowest quartiles were ≤0.41), whereas serum γ-linolenic acid concentration was associated with a higher FLI and higher odds for hepatic steatosis. The associations with the other PUFAs were generally weaker and nonsignificant. In the cross-sectional analyses, also the long-chain n-3 PUFAs had inverse associations. In most analyses, high estimated Δ5-desaturase activity was associated with lower risk and high estimated Δ6-desaturase activity with higher risk for NAFLD. CONCLUSIONS: In middle-aged and older Finnish adults, higher serum concentrations of total n-6 PUFAs and linoleic acid were associated with lower odds for future NAFLD.

Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial: a randomized controlled trial.

BACKGROUND: Vitamin D insufficiency is associated with risks of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited. OBJECTIVES: To investigate the effects of vitamin D3 supplementation on CVD and cancer incidences. METHODS: The study was a 5-year, randomized, placebo-controlled trial among 2495 male participants ≥60 years and post-menopausal female participants ≥65 years from a general Finnish population who were free of prior CVD or cancer. The study had 3 arms: placebo, 1600 IU/day, or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers, and cancer death. RESULTS: During the follow-up, there were 41 (4.9%), 42 (5.0%), and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (compared with placebo: HR: 0.97; 95% CI: 0.63-1.49; P = 0.89), and 3200 IU/d (HR: 0.84; 95% CI: 0.54-1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%), and 40 (4.8%) participants in the placebo, 1600 IU/d (HR: 1.14; 95% CI: 0.75-1.72; P = 0.55), and 3200 IU/d (HR: 0.95; 95% CI: 0.61-1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the subcohort, the mean baseline serum 25-hydroxyvitamin D concentration was 75 nmol/L (SD, 18 nmol/L). After 12 months, the concentrations were 73 nmol/L (SD, 18 nmol/L), 100 nmol/L (SD, 21 nmol/L), and 120 nmol/L (SD, 22 nmol/L) in the placebo, 1600 IU/d, and 3200 IU/d arms, respectively. CONCLUSIONS: Vitamin D3 supplementation did not lower the incidences of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline.

Caffeine content in newborn hair correlates with maternal dietary intake.

PURPOSE: High-maternal caffeine intake during pregnancy may be harmful for perinatal outcomes and future child health, but the level of fetal cumulative exposure has been difficult to measure thus far. Here, we present maternal dietary caffeine intake during the last trimester and its correlation to caffeine content in newborn hair after birth. METHODS: Maternal third trimester diets and dietary caffeine intake were prospectively collected in Kuopio Birth Cohort (KuBiCo) using a 160-item food frequency questionnaire (n = 2840). Newborn hair was collected within 48 h after birth and analyzed by high-resolution mass spectrometry (HRMS) for caffeine (n = 316). Correlation between dietary caffeine intake and neonatal hair caffeine content was evaluated from 203 mother-child pairs. RESULTS: Mean dietary caffeine intake was 167 mg/days (95% CI 162-172  mg/days), of which coffee comprised 81%. Caffeine in the maternal diet and caffeine content in newborn hair correlated significantly (r = 0.50; p < 0.001). Older, multiparous, overweight women, and smokers had the highest caffeine levels in the maternal diet, as well as in their newborn babies' hair. CONCLUSION: Caffeine exposure, estimated from newborn hair samples, reflects maternal third trimester dietary caffeine intake and introduces a new method to assess fetal cumulative caffeine exposure. Further studies to evaluate the effects of caffeine exposure on both perinatal and postnatal outcomes are warranted, since over 40% of pregnant women consume caffeine more than the current suggested recommendations (European Food Safety Association, EFSA recommendations).