In an 11-year study published in JAMA, male subjects, who followed a less nutritious diet but supplemented with a multivitamin found no clear impact on cardiovascular (CVD) risk or mortality.
"Intuitively, many had thought that men with 'poor' nutritional status at baseline may benefit more from long-term multivitamin use on cardiovascular outcomes. However, we did not see any evidence for this in our recent analysis," said co-author Dr Howard Sesso from the Division of Preventive Medicine and the Division of Aging at Brigham and Women’s Hospital.
"Given the continued high prevalence of multivitamin use, it remains critical for us to understand its role on nutritional status and other long-term health outcomes."
According to the researchers, the findings are all the more urgent considering the persistent and common use of multivitamins, particularly in older adults. Of equal significance is how much of an influence baseline nutritional status has on the long-term effects of multivitamin use.
Market analysts Euromonitor predicted the European dietary supplement market will be worth an estimated €7.9 bn by 2020.
Eastern Europe is expected to grow a further 18.9% by 2020.
This compares to around 6.3% in the Western European marketplace over the same period.
The study took data from The Physicians' Health Study II (PHS II), a randomised, large-scale, long-term trial that enrolled over 14,000 male doctors over the age of 50.
Of these subjects, 13 316 (91.0%) completed a food frequency questionnaire that was included in the analyses.
This questionnaire homed in on the effect various dietary factors had on baseline nutritional status.
These factors included intake of key foods, individual nutrients, dietary patterns (Alternate Healthy Eating Index (AHEI) and Alternate Mediterranean Diet (aMD) Score), and dietary supplement use that included vitamin B6, vitamin B12 and vitamin D.
Data for foods such as fruits and vegetables, whole grains, nuts, dairy products, and red and processed meats were also made available.
The study began in 1997, with continued treatment and follow-up through June 1, 2011.
The 13 316 male physicians receiving the active multivitamin exhibited no evidence of effect modification by various foods, nutrients, dietary patterns, or baseline supplement use on the effect of multivitamin use on cardiovascular disease end points.
However, significant effects were observed between multivitamin use and vitamin B6 intake on myocardial infarction (MI).
Other interactions of importance were observed between multivitamin use and vitamin D intake on CVD mortality and between multivitamin use and vitamin B12 intake on CVD mortality and total mortality.
"Our results suggest that multivitamin use among men with lower intake of major dietary factors did not lower risk of CVD or total mortality," the study said.
"However, the PHS II included male physicians, who were on average likely better nourished than the general population. Therefore, we may not have had the required ranges or extremes of dietary intake to sufficiently distinguish whether particular subgroups of men may benefit more or less from multivitamin use based on baseline nutritional status.
"Optimally, the evaluation of nutritional biomarkers would provide a more objective assessment of nutritional status and complement our findings."
Responding to the findings, Duffy MacKay, senior vice president, scientific & regulatory affairs at the Council of Responsible Nutrition said that science had already demonstrated the value of the multivitamin.
"While we are disappointed to see the null results of this study, by no means are we discouraged. The multivitamin serves many roles—from filling nutrient gaps to preventing neural tube birth defects—and is trusted as a go-to nutrition insurance policy by nearly a hundred million Americans each year. Only four years ago, the Physicians’ Health Study II found the multivitamin may have potential benefit for the prevention of cancer in a well-nourished male population.
"This well-designed study, which found no consistent impact of nutritional status on the effect of multivitamin use on cardiovascular disease risk, reminds us to manage expectations for the role of multivitamins.
"For consumers, the key takeaway of this study is that the multivitamin is not a panacea, but at the very least, given the nutrient shortfalls in our population, it can reliably fill nutrient gaps."
Comparative studies that have looked into the role of baseline nutritional status on CVD risk were limited to single or specific combinations of vitamins and minerals at higher amounts than in the current study.
The Women’s Antioxidant and Folic Acid Cardiovascular study tested a combination of folic acid (2.5 milligrams per day (mg/d)), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d) among female health professionals at higher risk of CVD.
They found no evidence of effect modification by baseline folate intake or multivitamin use.
In contrast, the China Stroke Primary Prevention trial tested a folic acid supplement (0.8 mg/d) among hypertensive women and men and reported stronger reductions in stroke among participants with a baseline folate blood concentrations lower than 5.6 ng/mL.
One consideration highlighted in the current study was multivitamin use in older men, where impaired nutrient absorption and subsequent nutritional status can alter vitamin and mineral requirements.
Diet alone may not be enough to meet these changes in nutritional requirements, said the authors.
Vitamin B12 deficiency is highly prevalent among adults 65 years or older because of poor diet and diminished absorption associated with age.
“In our analyses, men 70 years or older who were in the highest tertiles of the AHEI and more adherent to the aMD had reductions in MI risk with multivitamin use,” the study commented.
Despite the conclusions reached the team highlighted the inconsistently in their findings that were observed for selected dietary factors. End points too were observed that required multiple testing for verification.
“The PHS II included physician participants, who had on average a healthier diet than the general population,” the study explained.
“Therefore, the generalizability of these results to populations with different dietary patterns is subject to caution.”
Funding for this work was provided by Pfizer along with the National Institutes of Health, Council for Responsible Nutrition Foundation, and COFAS Marie Curie Fellowship.
Source: JAMA Cardiology
Published online ahead of print: doi:10.1001/jamacardio.2017.0176
“Effect of Baseline Nutritional Status on Long-term Multivitamin Use and Cardiovascular Disease Risk. A Secondary Analysis of the Physicians’ Health Study II Randomized Clinical Trial”
Authors: Susanne Rautiainen, J. Michael Gaziano, William Christen et al