Health effects of vitamin D
Vitamin D deficiency is widespread throughout the world, and a few countries, like Finland, have fortified some foods with vitamin D. Although this has raised the average serum levels, a large proportion still has serum 25-hydroxyvitamin D [25(OH)D] levels <50 nmol/L, generally agreed to indicate deficiency. In our Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) population 65% had serum 25(OH)D <50 nmol/L and the average serum values exceeded 50 nmol/L only during the summer months and declined rapidly in the fall. We also found that low serum 25(OH)D was a significant risk factor for mortality in this study population.
There is abundant evidence from population studies that vitamin D insufficiency is associated with higher risk of chronic diseases and other adverse health outcomes, but there is no data from large randomized controlled trials (RCT) in general populations whether improvement of vitamin D status by supplementation can improve health. However, most RCTs were not either designed to evaluate the impact of vitamin D on non-skeletal outcomes, or were small in size, or the dose of vitamin D was too low or the duration too short, to be able to show an effect. In addition, the role of the quite marked inter-individual variation in the vitamin D status [serum 25(OH)D] and in the responsiveness to vitamin D supplementation needs to be investigated.
The Finnish Vitamin D Trial (FIND) started in September 2012. It is a 5-y trial of the benefits and possible risks of vitamin D3 supplementation on the incidence of major chronic diseases, their risk factors and self-rated health among men ≥60 y and women ≥65 y from the general population who were free of cardiovascular disease and cancer at baseline. The 2500 participants that started in the study were randomized into three groups: 40 μg of vitamin D3, 80 μg of vitamin D3 or placebo.
Objectives of the study are to 1) investigate the impact of 5-year vitamin D3 supplementation vs placebo on physiological effects andhealth outcomes, 2) evaluate and identify genetic and environmental factors that contribute to the inter-individual variation in the responsiveness of serum 25(OH)D concentrations to supplementation and whether these factors have a role in determining the health effects of vitamin D supplementation, and 3) investigate the impact of 5-year vitamin D supplementation on balance, muscle strength, bone mineral density, body composition and fractures.
The cohort is followed with annual study forms and data from national registries. A representative subgroup of 551 subjects visits the study site five times during the study for more detailed investigations. After the trial, the follow-up for the major chronic disease events as well as for mortality will be continued from the national registries for a minimum of 10 y.
Although several large vitamin D RCTs have recently started, FIND is the only trial in such northern latitudes and one of the few trials with two different vitamin D doses. This provides a unique opportunity to investigate the dose-response on the health effects of vitamin D supplementation.