Cancer is the second leading cause of mortality for adults; it is considered an age-related disease. To make matters worse, accelerated aging associated with lifestyle-risk factors, such as poor diet and lack of exercise, correlates with a higher incidence of cancer.
High quality multi-modality research is rare, especially combining natural products and exercise. Investigators tend to look at one agent or intervention at a time—a reductionist approach—as opposed to exploring the bio-synergistic effects of, well, how many of us actually live.
An elegant if not complex study, recently published in Frontiers of Aging, focused on more than 2,000 healthy adults over 70 years old. The participants were randomized to participate in variations of these components: vitamin D, omega-3 fatty acids, a home exercise program.
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The three-year-long, multi-country, European-based study was led by the consortium DO-HEALTH Research Group. Two of the most accomplished American researchers on nutrition, epidemiology, and dietary supplements served as scientific advisory board members to the research organization, and co-authored the published paper: Drs. Walter C. Willet and JoAnn E. Manson.
Below is an overview of the DO-HEALTH trial and outcomes, and a link to the full open-access published paper.
Study objective: To test if two specific dietary supplements (groups taking both or one) taken independently of a simple home exercise plan (SHEP), or taken in conjunction with that plan, has an impact on the risk of an invasive cancer diagnosis.
Design: A three-year, multi-center, 2x2x2 factorial design double-blind, randomized trial to test the benefit of individual and combined interventions.
Number of participants: 2,157
Participant criteria: Generally healthy, 70+ years old. Mean age: 74.9 years.
Setting: Between December 2012 and December 2017 (total study period was five years) in five European countries.
Interventions: Supplemental 2000 IU/day vitamin D3, and/or 1 gram/day of marine omega-3s, and/or SHEP, compared to placebo and control exercise.
Endpoint (primary outcome): Time-to-development for any invasive cancer required treatment.
Out of a total of 2,157 participants:
- 81 invasive cancer diagnoses
- The three individual treatments versus control: 36 versus 45 cancer diagnoses
- Vitamin D3 arm versus control: 36 versus 45 cancer diagnoses
- Omega-3 arm versus control: 32 versus 49 cancer diagnoses
- SHEP arm versus control: 35 versus 46 cancer diagnoses
- Combinations of two treatments:
~Vitamin D3 and omega-3 versus control: 15 versus 28 cancer diagnoses
~Vitamin D3 and SHEP versus control: 11 versus 21 cancer diagnoses
~Omega-3 and SHEP versus control: 12 versus 26 cancer diagnoses
- Combination of all three treatments combined: 4 versus 12 cancer diagnoses
Conclusion: Supplementation combining vitamin D3 and omega-3, plus simple home exercise program, showed statistically relevant reduction in cancer risk for generally healthy adults over 70 years of age.
…this is the first randomized-controlled trial to investigate the combination of three complementary treatments for the prevention of cancer and 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 aged 70 and older. Based on our findings, with the triple combination, we would need to treat 35 persons in order to prevent one incident case of cancer at 3 years follow-up. ~DO-HEALTH trial authors
Read the complete published paper: 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
Being a longtime advocate of lifestyle having significant impact on reducing disease risk and improving cancer survivorship, and given the stats at the beginning of this piece—leading cause of mortality in adults, aging a factor, not many studies to correlate supplementation and exercise—there is great value in this published paper. The paper itself is a boon to an older demographic and, perhaps, a proactive wake-up call for those of us who are not quite in that age group.
As such, with a mean age of 75 years, and study duration of five years—combined with a generally healthy set of participants—the investigators chose the participant criteria wisely.
The authors discuss the study of multiple anti-cancer agents for blocking multiple pathways for cancer development, and the paucity of research looking at multiple pathways to prevent cancer onset. They also describe research heretofore focused on screenings, vaccines, and smoking cessation (in regard to lung cancer).
The published paper also highlights the current literature and inconclusive findings as it relates to cancer prevention and the study of vitamin D3 and omega-3s and the prevailing mechanisms of action found for each.
Specific to the hormone vitamin D3: it inhibits the growth of cancer by regulating several genes responsible for cell proliferation and differentiation. And specific to omega-3: it may inhibit carcinogenesis by suppression of inflammation, cell proliferation, and angiogenesis (the spread of cancer cells through blood vessels).
Exercise is generally thought to reduce cancer risk by decreasing inflammation and strengthening immune function. Observational studies have consistently supported findings correlating higher levels of physical activity and lower incidences of cancer onset and cancer death.
Final Thoughts and Observations
I will be the first to recognize that the complexity of so many variables and arms of this study—the 2x2x2 multi-factorial design—make it challenging for the average layperson, who is neither a science writer nor a biomedical researcher, to fully understand all the statistics contained therein.
As an example of this complexity, notice that the number of invasive cancers for each arm do not add up to the total number of invasive cancers. Again, the byproduct of the 2x2x2 multi-factorial design.
I recall in 2012 working on a study design with a group at Harvard that would incorporate my integrative oncology and lifestyle medicine approach to manage the leukemia I was hosting. I was pushing for a truly comprehensive, multi-modal, non-reductionist design.
We all agreed that it would be the biostatistician who would be the one doing the heavy lifting, figuring out how best to design, the small study and what data to ultimately collect. The point is, once you bring quite a few variables into a study design, things can get really complex really fast.
Congratulations to the DO-HEALTH Research Group consortium for undertaking this high quality investigation and elegant, sophisticated study design. The outcomes are remarkable, and support a sensible approach to utilizing vitamin D3 to maintain a healthy blood serum level (25-hydroxyvitamin D), eating plenty of omega-3 rich cold water fish (ex.: wild salmon, halibut, mackerel, sardines, cod), supplementing accordingly, and getting plenty of consistent exercise.
Full circle, from my perspective as both a cancer coach and someone who has personally incorporated this basic approach into a larger program for over three decades, the time to act is now… and yes, of course, the common refrain follows: more studies are desperately needed.
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