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

Authors: BISCHOFF-FERRARI, HEIKE - University Hospital Zurich; WILLETT, WALTER - Harvard University; MANSON, JOANN - Harvard University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MANZ, MARKUS - University Hospital Zurich; THEILER, ROBERT - University Hospital Zurich; BRANDLE, KILIAN - University Hospital Zurich; VELLAS, BRUNO - University Hospital Zurich; RIZZOLI, RENE - Geneva University Hospital; KRESSIG, RETO - University Of Basel; STAEHELIN, HANNES - University Of Basel; DA SILVA, JOSE - University Of Coimbra; AMBRECHT, GABRIELE - Charite' University Hospital Berlin; EGLI, ANDREAS - University Hospital Zurich; KANIS, JOHN - University Of Sheffield; ORAV, ENDEL - Harvard University; GANGLER, STEPHANIE - University Hospital Zurich

Submitted to: British Medical Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2022
Publication Date: 4/25/2022
Citation: Bischoff-Ferrari, H.A., Willett, W.C., Manson, J.E., Dawson-Hughes, B., Manz, M.G., Theiler, R., Brandle, K., Vellas, B., Rizzoli, R., Kressig, R.W., Staehelin, H.B., Da Silva, J.A., Ambrecht, G., Egli, A., Kanis, J., Orav, E.J., Gangler, S. 2022. 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. British Medical Journal. 3:852643. https://doi.org/10.3389/fragi.2022.852643.
DOI: https://doi.org/10.3389/fragi.2022.852643

Interpretive Summary: This analysis was done to examine the impact of 3 public health interventions on new cases of cancer over a 3-year period in 2,157 healthy adults age 70 years and older who participated in the DO-HEALTH clinical trial carried out in 5 European countries. The interventions in this trial, each with a control group, were: 2000 IU per day of vitamin D, 1 g per day of marine omega-3s, and a simple home strength exercise program. The main results of the trial have been published. During the trial, information on new cancers was collected and 81 cases of invasive cancer were diagnosed. When the 3 interventions were considered individually, there were fewer cases of cancer in each than when compared with their control groups, but the differences were not significant. In contrast, the combination of any two of the three interventions was associated with a significant risk reduction of new cases of invasive cancer of 45 to 50%, and the combination of the 3 interventions was associated with a risk reduction of 61%. These findings suggest that the combination of daily vitamin D3, supplemental marine omega-3s, and a simple home exercise program may be effective in the prevention of invasive cancer among generally healthy adults age 70 and older.

Technical Abstract: Objective: 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. Design: The DO-HEALTH trial is a three-year, multicenter, 2x2x2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions. Setting: The trial was conducted between December 2012 and December 2017 in five European countries. Participants: Generally healthy community-dwelling adults 70 years and older were recruited. Interventions: Supplemental 2000 IU/day of vitamin D3, and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise. Main outcome: 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. Results: 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 D3, 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 D3; 0.56 (0.30-1.04; 11 vs. 21) for vitamin D3 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). Conclusion: Supplementation with daily high-dose vitamin D3 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 and older.