Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial

The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer. The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions. The trial was conducted between December 2012 and December 2017 in five European countries. Generally healthy community-dwelling adults ≥70 years were recruited. Supplemental 2000 IU/day of vitamin D , and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise. In this pre-defined exploratory analysis, time-to-development of any verified invasive cancer was the primary outcome in an adjusted, intent-to-treat analysis. In total, 2,157 participants (mean age 74.9 years; 61.7% women; 40.7% with 25-OH vitamin D below 20 /ml, 83% at least moderately physically active) were randomized. Over a median follow-up of 2.99 years, 81 invasive cancer cases were diagnosed and verified. For the three individual treatments, the adjusted hazard ratios (HRs, 95% CI, cases intervention versus control) were 0.76 (0.49-1.18; 36 vs. 45) for vitamin D , 0.70 (0.44-1.09, 32 vs. 49) for omega-3s, and 0.74 (0.48-1.15, 35 vs. 46) for SHEP. For combinations of two treatments, adjusted HRs were 0.53 (0.28-1.00; 15 vs. 28 cases) for omega-3s plus vitamin D ; 0.56 (0.30-1.04; 11 vs. 21) for vitamin D plus SHEP; and 0.52 (0.28-0.97; 12 vs. 26 cases) for omega-3s plus SHEP. For all three treatments combined, the adjusted HR was 0.39 (0.18-0.85; 4 vs. 12 cases). Supplementation with daily high-dose vitamin D plus omega-3s, combined with SHEP, showed cumulative reduction in the cancer risk in generally healthy and active and largely vitamin D-replete adults ≥70 years. ClinicalTrials.gov, Identifier: NCT01745263.