More Vitamin D Not Better for Reducing Cancer or CVD Incidence

Roxanne Nelson, RN, BSN

January 10, 2022

Vitamin D supplementation did not appear to influence the incidence of cancer or major cardiovascular disease (CVD) events in older adults who largely already had adequate vitamin D levels, according to a new randomized controlled study.

In the cohort of nearly 2500 healthy individuals, the researchers found no differences in cancer or CVD incidence over 5 years between the groups randomly assigned to vitamin D supplementation and to placebo.

The findings, published online January 4 in the American Journal of Clinical Nutrition, may be influenced by the fact that most participants had sufficient vitamin D levels at baseline, and thus received higher than recommended doses of vitamin D during the study.

"Vitamin D3 supplementation with 1600 or 3200 IU/day for 5 years did not reduce the incidence of major CVD events, any invasive cancer, or mortality among generally healthy and mostly vitamin D sufficient older adults in Finland," write the authors, led by Jyrki Virtanen, RD, PhD, associate professor of nutrition and public health at University of Eastern Finland, Kuopio.

"The low number of subjects with low vitamin D concentrations was a bit of a surprise for us also, but it likely reflects the quite successful food fortification policy in Finland, " Virtanen told Medscape Medical News.

Prior research has found that vitamin D insufficiency is associated with a higher risk of nearly all diseases. Although the evidence on the benefits of vitamin D supplementation remains more limited, three meta-analyses published in 2019 reported a consistent and significant 13% reduction in cancer mortality in those who received vitamin D supplements.

In this study, Virtanen and colleagues investigated the effects of vitamin D3 supplementation on cancer and CVD incidence in a cohort of 2495 healthy participants.

Men 60 years or older and women 65 years or older were randomly assigned to one of three groups: placebo, 40 micrograms (1600 IU) of daily vitamin D3, or 80 micrograms (3200 IU) of daily vitamin D3.

Data collected at baseline and throughout the trial included serum 25(OH)D concentrations, nutrition, sun exposure, medication use, mental health, and other factors that could affect the risk of disease.

The study's primary endpoints were incident of major CVD and invasive cancer. Secondary endpoints included incidence of myocardial infarction, stroke, and CVD mortality as well as site-specific cancers and cancer death.

Follow-up occurred via annual study questionnaires and national registry data. A representative sub-cohort of 551 participants had more detailed in-person evaluations. In the sub-cohort, mean serum 25(OH)D concentration was 75 nmol/L (30 ng/mL) at baseline; 9.1% had concentrations < 50 nmol/L (20 ng/mL) and 50.0% had concentrations ≥ 75 nmol/L (30 ng/mL).

The authors identified no major differences between the three arms at baseline, but noted that compared to the overall study population, those in the sub-cohort were younger, more likely to use their own vitamin D supplements, and more likely to rate their health as good or excellent.

Among 503 participants that had complete data from baseline, the mean increase in serum 25(OH)D in participants receiving 1600 IU/day vitamin D3 was 23.4 nmol/L (9.4 ng/mL) and 43.6 nmol/L (17.4 ng/mL) in the arm receiving 3200 IU/day between baseline and 6 months. The authors observed a small additional increase in levels between the 6-month and 12-month visits, but few changes in vitamin D3 levels in the placebo arm.

At the 5-year follow-up, major CVD events occurred in 4.9% of participants in the placebo arm, 5% in those in the 1600 IU/d arm (hazard ratio [HR], 0.97), and 4.3% of those in the 3200 IU/d arm (HR, 0.84; P = .44). Invasive cancer at follow-up was diagnosed in 4.9% of placebo recipients, 5.8% of those on 1600 IU/d supplementation (HR, 1.14; P = .55), and 4.8% in the 3200 IU/d group (HR, 0.95; P = .81). No significant differences were observed in the secondary endpoints or in total mortality.

The authors did not conduct a subanalysis in participants who had low 25(OH)D concentrations levels at baseline because "there were too few participants to do any meaningful analyses," said Virtanen, who noted that blood samples were available for a representative subgroup of 550 subjects and only 9% of them had low 25(OH)D concentrations at baseline.

Virtanen noted that future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status.

The study was supported by funding from the Academy of Finland (#137826), University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation. Virtanen has disclosed no relevant financial relationships.

Am J Clin Nutr. 2022;nqab419. Abstract

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