5-year trial shows high-dose vitamin D does not prevent CVD, cancer

Vitamin D3 supplementation, when taken in amounts that exceeded the recommended daily allowance, did not lower the occurrence of major CVD events or invasive cancer among older adults, data from a 5-year randomized controlled trial showed.

The NIH recommends that adults aged 51 to 70 years consume 600 IU of vitamin D daily and adults aged 70 years and older consume 800 IU daily. However, previously published research has suggested that 1 billion people worldwide may have deficient or insufficient levels of vitamin D.

Jyrki K. Virtanen, PhD, an associate professor of nutrition and public health at the Institute of Public Health and Clinical Nutrition at the University of Eastern Finland, and colleagues reviewed data from 2,495 “generally healthy” older white adults (mean age, 68.2 years; 43% women) who lived in Finland. According to the researchers, the country’s location in the Northern hemisphere limits cutaneous vitamin D production to the summer months. In the study, most of the adults gave their baseline blood in the spring, fall or winter, “making it unlikely” that vitamin D production in the skin contributed to the adults’ baseline serum 25-hydroxyvitamin D levels.

The participants were randomized in an approximate 1:1:1 ratio to receive either 1,600 IU of vitamin D3 daily, 3,200 IU of vitamin D3 daily or placebo. All participants, including those assigned to placebo, were permitted to use their own vitamin D supplements of up to 800 IU per day. However, most participants said they did not use personal vitamin D supplements during the study period, according to the researchers.

Most participants (n = 1,944) were monitored through annual questionnaires and national registry data. The researchers assessed a representative subcohort of 551 adults during more detailed, in-person visits. Participants in the subcohort tended to be younger, have a higher education, were more likely to be married, more likely to consume their own vitamin D supplements and rated their health as “good” or “excellent,” had taken a vacation in a sunny place more often during the prior 12 months and more commonly used sunscreen during the summer months, according to the researchers.

Virtanen and colleagues reported in the American Journal of Clinical Nutrition that a major CVD event — which they defined as a composite endpoint of myocardial infarction, stroke and death from CVD — occurred in 4.9% of the placebo cohort, 5% of the 1,600 IU daily cohort (HR vs. placebo = 0.97; 95% CI, 0.63-1.49) and 4.3% of the 3,200 IU daily cohort (HR vs. placebo = 0.84; 95% CI, 0.54-1.31) during the follow-up period. Invasive cancer was diagnosed in 4.9% of the placebo cohort, in 5.8% of the 1,600 IU daily cohort (HR vs. placebo = 1.14; 95% CI, 0.75-1.72) and in 4.8% of the 3,200 IU daily cohort (HR vs. placebo = 0.95; 95% CI, 0.61-1.47). Nineteen adults had death as their first incident event during the follow-up period; there was no statistically significant differences in the event rates between the three cohorts.

Among participants in the subcohort, the mean baseline serum 25-hydroxyvitamin D concentration was 75 nmol/L. After 1 year, these concentrations were 73 nmol/L in the placebo cohort, 100 nmol/L in the 1,600 IU daily cohort and 120 nmol/L in the 3,200 IU daily cohort. Among 1,609 adults who completed the last questionnaire, 74.8% said they had consumed all the pills during the study and 95.3% said they consumed 80% or more of the pills.

“In conclusion, vitamin D3 supplementation with 1,600 or 3,200 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,” Virtanen and colleagues wrote. “As in other similar large trials with mainly null findings, the baseline vitamin D levels have been sufficient in a large majority of the participants. Future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status." 

References:

• Taking high-dose vitamin D supplements for five years did not affect the incidence of cardiovascular disease or cancer. https://www.eurekalert.org/news-releases/939321. Published Jan. 5, 2022. Accessed Jan. 6, 2022.
• Virtanen JK, et al. Am J Clin Nutr. 2022;doi:10.1093/ajcn/nqab419.
• Vitamin D. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed Jan. 6, 2022.