What next?

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. 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.

Although randomisation reduces confounding, relying exclusively on the results of randomised trials also has limitations. 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).

Nutrients obtained from foods and supplements may confer different health effects. The Cancer Prevention Study (CPS)-II Nutrition Cohort found that supplemental calcium intake at ≥1000 mg/day was associated with an increased risk of all-cause mortality in men whereas high levels of calcium intake from foods had no harm.48 Among US adults in the National Health and Nutrition Examination Survey, adequate intake of nutrients from foods, but not supplements, was associated with a lower risk of all-cause mortality.6 The benefits of nutrient intake from foods may reflect synergistic interactions among multiple nutrients and other bioactive substances in foods.

The effect of supplements in specific populations warrants further investigation. Older adults are at an increased risk of malnutrition because of reduced nutrient intake and age related decreases in the bioavailability of some micronutrients. Vitamin D supplementation is recommended for breastfed infants before the introduction of whole milk and solid foods. Supplements may be more effective in reducing the risk of non-communicable disease in specific ethnic groups or people with low micronutrient intake from foods.28 With a recent increase in the proportion of people reporting that they follow restricted dietary patterns such as ketogenic, Palaeolithic, vegan, and vegetarian diets, the value of supplements to meet the needs of these specific populations requires evaluation. In addition, potential nutrient-gene interactions have rarely been examined in studies of dietary supplements. Future studies on the role of nutrigenetics should help refine and personalise targeted recommendations for supplement use (box 2).

It is also important to recognise that the need for nutrient supplements is different in countries where nutrition deficiency is common. Ensuring adequate nutrition through food fortification and nutrient supplementation can be crucial to prevent serious adverse outcomes of nutrient deficiencies in low and middle income countries, especially among children <5 years, for whom malnutrition contributes to more than half their deaths.15

In summary, 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. 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. These efforts, coupled with the integration of new research approaches, will better inform clinical practice and public health policies.