Association of folate intake with cardiovascular-disease mortality and all-cause mortality among people at high risk of cardiovascular-disease.

BACKGROUND & AIMS: Due to the beneficial effect of folate on cardiovascular disease (CVD), folic acid supplementation is a more common practice among people at high-risk of CVD. However, long-term prospective investigations regarding the association of folate-intake with CVD-mortality and all-cause mortality among this specific population are still lacking. Therefore, this study aims to assess the association of folate-intake with CVD-mortality and all-cause mortality. METHODS: A total of 14,234 participants at high-risk of CVD were enrolled. Total folate equivalent (TFE), dietary folate equivalent (DFE), food folate, folic acid in fortified food, folic acid supplements, serum folate and red blood cell (RBC) folate were measured. The main outcome measures were CVD-mortality and all-cause mortality from baseline until 31 December 2015. RESULTS: During the 98,890 person-year follow-up, 2036 deaths including 682 deaths due to CVD were documented. After multivariate adjustment, a J shaped association was found: modest intake of TFE and DFE was associated with lower risk of CVD-mortality and all-cause mortality, whereas higher intake did not persistently reduce these risks. Compared to the participants without folic acid supplementation matched 28-covariates using propensity score, folic acid supplementation was associated with higher risk of CVD-mortality (HR:1.44, 95%CI:1.06-1.97, P = 0.022) and all-cause mortality (HR:1.28,95%CI:1.09-1.51, P = 0.003). The levels of serum-folate and RBC-folate in participants with folic acid supplementation were significantly greater than participants without folic acid supplementation (41.8 nmol/l vs. 64.2 nmol/l, P < 0.001 for serum-folate; 1201 nmol/l vs. 1608 nmol/l, P < 0.001 for RBC-folate). Compared with the lowest-quintile of serum-folate, the second-quintile was consistently associated with CVD-mortality (HR:0.72, 95%CI:0.53-0.99, P = 0.048) and all-cause mortality (HR:0.78, 95%CI:0.64-0.94, P = 0.013). Compared to the lowest-quintile of RBC-folate, the second-quintile was associated with lower all-cause mortality (HR:0.71,95%CI:0.56-0.90, P = 0.005), whereas the highest-quintile was associated with higher CVD-mortality (HR:1.40,95%CI:1.02-1.93, P = 0.030). The J shaped association of serum-folate and RBC-folate with CVD-mortality and all-cause mortality was also demonstrated, further supporting the results of TFE and propensity score analysis. CONCLUSIONS: This study suggested the beneficial effects of modest folate-intake on the improvement of long-term survival, and emphasized the potentially deleterious effects of excess folic acid supplementation among US adults at high-risk of CVD.

The joint effect of energy reduction with calcium supplementation on the risk factors of type 2 diabetes in the overweight population: a two-year randomized controlled trial.

Both excessive energy intake and low calcium intake are inversely associated with the aging-related diseases, particularly for type 2 diabetes mellitus(T2DM). This study examined whether energy reduction coupled with calcium supplementation aided in the prevention of T2DM among the overweight population. A randomized controlled trial(RCT) of 1021 overweight participants was performed, in which participants were randomly assigned to 4 groups: 1) energy-reduction group(ERG), 2) calcium supplementation group(CSG), 3) energy-reduction with calcium supplementation group(ER-CSG), 4) control group(CG). Nutritional habits, anthropometric and diabetes-related indicators were measured at baseline and each follow-up time. To analyze the separate effects of dietary energy reduction and calcium supplementation, ERG and ER-CSG were integrated into ERGs. Similarly, CSG and ER-CSG were integrated into CSGs. Compared to the non-energy-reduction groups(NERGs), ERGs had lower values of ΔBMI(-0.9kg/m2), ΔFSG (-0.34mmol/L), ΔHbA1c(0.16%), and ΔHOMA-IR(-0.13), and higher value of ΔGutt index(-5.82). Compared to the non-calcium supplementation groups(NCSGs), the ΔGutt index(-5.46) in CSGs showed a significant decrease. Moreover, these risk factors for T2DM were most effectively ameliorated in ER-CSG group with the decreased values of ΔFSG(-0.42mmol/L), ΔGutt index(-0.73), and the slowest increasing rate value of Δ2h-glucose(0.37mmol/L). This RCT demonstrated that energy-reduction with calcium supplementation was a useful dietary intervention strategy for preventing the development of T2DM in the overweight population.