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

• Published in: The American journal of clinical nutrition Vol. 115; no. 5; pp. 1300 - 1310
• Main Authors: Virtanen, Jyrki K, Nurmi, Tarja, Aro, Antti, Bertone-Johnson, Elizabeth R, Hyppönen, Elina, Kröger, Heikki, Lamberg-Allardt, Christel, Manson, JoAnn E, Mursu, Jaakko, Mäntyselkä, Pekka, Suominen, Sakari, Uusitupa, Matti, Voutilainen, Ari, Tuomainen, Tomi-Pekka, Hantunen, Sari
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2022; Oxford University Press; American Society for Clinical Nutrition, Inc
• Subjects: 25-Hydroxyvitamin D; Aged; Calciferol; Cancer; cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cerebral infarction; Cholecalciferol; Dietary Supplements; Double-Blind Method; Editor's Choice; elderly; Female; Finland - epidemiology; Health risks; Humans; Invasiveness; Male; Medborgarcentrerad hälsa (Mech); Menopause; Mortality; Myocardial infarction; Neoplasms - drug therapy; Neoplasms - epidemiology; Neoplasms - prevention & control; Older people; Original Research Communications; Placebos; Post-menopause; randomized controlled trial; Research on Citizen Centered Health, University of Skövde (Reacch US); supplementation study; Supplements; Vitamin D; Vitamin D - therapeutic use; Vitamin D Deficiency - complications; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - epidemiology; Vitamin D3; Vitamin E; Vitamins - therapeutic use; Finland; cardiovascular disease; RCT; VDR; vitamin D; elderly; randomized controlled trial; CVD; VITAL; supplementation study; ViDA; 25(OH)D; FIND; cancer
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.1093/ajcn/nqab419

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.
To investigate the effects of vitamin D3 supplementation on CVD and cancer incidences.
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.
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.
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.
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