Writing in the BMJ, the team says the effect of vitamin and mineral supplements on the risk of non-communicable diseases in “generally healthy” populations is controversial.
They point to randomised trial evidence that does not support use of vitamin, mineral, and fish oil supplements to reduce the risk of these diseases, such as cardiovascular disease, cancer, or T2 diabetes.
“To date, randomised trials have largely shown no benefit of vitamin, mineral, and fish oil supplements on the risk of major non-communicable diseases in people without clinical nutritional deficiency,” says the team led by Dr Fang Fang Zhang, associate professor at the Friedman School of Nutrition Science and Policy at Tufts University.
“These results contrast with findings from observational studies, where supplemental nutrient intakes are often associated with a reduced risk of these diseases.
“The apparent associations from observational studies may result from unknown or unmeasured confounding factors such as socioeconomic status and lifestyle factors, including a better overall diet.”
The team points to a review of 15 randomised trials that appears to confirm the lack of benefits of supplements on cardiovascular events, mostly among patients with risk factors.
This review, along with others focuses on vitamins, minerals and omega-3 fatty acid intake, which has shown some benefits, namely a reduction in myocardial infarction (heart attack) cases.
This result is largely consistent with findings from meta-analyses that fish oil supplementation did not have substantial effects on the primary or secondary prevention of cardiovascular disease.
However, a meta-analysis including the most recent trials reported a significant reduction in risk of myocardial infarction.
Folic acid, vitamins B12 & B6
Along with colleagues from Ulster University and the University of British Columbia, the team also highlight randomised folic acid trials, alone or in combination with vitamins B12 or B6, that found significant reductions in plasma homocysteine levels but found no reduction in total cardiovascular events.
Another systematic review reported a reduced risk of stroke in association with supplementation of homocysteine lowering B vitamins, but the result was largely driven by one large trial in China.
The Vitamin D and Omega-3 Trial (VITAL), one of the few randomised trials of supplements for primary prevention of cardiovascular disease, found no effect of vitamin D supplementation (2000 IU/day) on its primary endpoint (myocardial infarction, stroke, or cardiovascular death) in healthy people.
“Current evidence does not support recommending vitamin or fish oil supplements to reduce the risk of non-communicable diseases among populations without clinical nutritional deficiency,” the team says.
“Continuing efforts are warranted to further understand the potentially different roles of nutrients from foods versus supplements in health promotion among a generally healthy population as well as individuals or groups with specific nutritional needs, including those living in low- and middle-income countries.”
The team also examine the role of vitamin and mineral supplements in cancer risk, with evidence suggesting potential harm.
The α-Tocopherol, β-Carotene Cancer Prevention Study reported an 18% increase in relative risk among smokers randomised to β-carotene (20 milligrams per day (mg/day)) compared with those who did not.
Meanwhile, the Selenium and Vitamin E Cancer Prevention Trial found that vitamin E (400 International Unit per day (IU/day)) supplementation was associated with a 17% increase in prostate cancer risk among men.
“Randomised trials have failed to detect a benefit of vitamin D supplementation, alone or combined with calcium, on cancer risk at either high or low doses despite some evidence suggesting reduced total cancer mortality,” the team says. “The limited evidence on fish oil supplementation suggests it does not reduce cancer risk.”
Type 2 diabetes
The team also point to current evidence as unsupportive of the use of supplements with vitamins C or E, β-carotene, or fish oil to reduce the risk of type 2 diabetes, although they acknowledge the overall evidence from randomised trials is limited.
A recent placebo-controlled trial of vitamin D supplementation (4000 IU/day) failed to reduce the risk of type 2 diabetes despite significantly increasing serum 25-hydroxyvitamin D concentrations.
“Although randomisation reduces confounding, relying exclusively on the results of randomised trials also has limitations,” the team admits.
“Trials are often conducted among high risk populations with pre-existing conditions, so the findings may not be applicable to healthy individuals.
“Supplements may also have health benefits for population subgroups, such as people with inadequate nutrient intake from foods, but randomised trials are not usually designed to evaluate subgroup differences.
“Furthermore, financial and practical constraints mean that most trials are able to investigate only a single dose, which may result in selection of a dose that is either too low (no efficacy) or too high (untoward outcomes).”
Published online ahead of print: doi.org/10.1136/bmj.m2511
“Health effects of vitamin and mineral supplements.”
Authors: Fang Fang Zhang et al.