Vitamin research — Preparing for the Future

“During the last decade, approaches to evidence-based medicine, with its heavy reliance on the randomized controlled trial (RCT), have been adapted to nutrition science and policy (1). However, there are distinct differences between the evidence that can be obtained for the testing of drugs using RCTs and that needed for the development of nutrient requirements or dietary guidelines: 1) medical interventions are designed to cure a disease not produced by their absence, while nutrients prevent dysfunction that would result from their inadequate intake; 2) drug effects are generally intended to be large and with limited scope of action, while nutrient effects are typically broad in scope and comparably small in effect size; 3) drug effects can be tested against a non-exposed (placebo) control group, whereas it is impossible and/or unethical to attempt to use a zero-intake group for nutrient trials; and 4) therapeutic drugs are intended to be efficacious within a relatively short term while the impact of nutrients on the reduction of risk of chronic disease may require decades to demonstrate.

Not surprisingly, RCTs investigating the effects of micronutrient supplementation on the prevention of multi-factorial chronic diseases have most often failed to show significant benefits. However, there is strong epidemiological evidence linking increased micronutrient intake (via food and/or supplements) to reduced risks of a range of diseases. Such RCTs (and their meta-analyses) are therefore often flawed, not so much in their conduct but in their design (2). For example, the control group’s intake of the nutrient under study may not be low enough, or the participants in the treatment group may already have a sufficient intake of the nutrient at the beginning of the study (therefore removing the need for supplementation). It is also impos-sible to let the nutrient under study manifest its own proper effect if the treatment group does not already have an adequate intake of other essential nutrients. For all these reasons, it would be useful to find some alternatives to RCTs that better reflect people’s dietary patterns and the unique features of nutrients as well as recognizing the need to deal with uncertainty arising from situations where we are unable to obtain evidence from RCTs. We cannot be as confident in nutrient recommendations as we can in those for drugs (and nutrients with a high benefit-risk ratio may require less certainty of efficacy). Unlike for drugs, where irrefutable proof of efficacy should always be demanded, decisions about nutrient recommendations should instead be based on whether the observational evidence links insufficient (or excessive) intake to probable harm.

The insights gained from the last 100 years of vitamin research and its applications have contributed sub-stantially to our fundamental understanding of biology and, more importantly, to the promotion of human health. There is no reason to believe that the next 100 years will be any less fruitful if we are committed to preparing for them, particularly by changing four critical nutrition paradigms:

• First, we must move beyond the concept of preventing vitamin deficiencies and inadequacies. We must instead focus on establishing health and achieving optimal physiological function. Each essential vitamin possesses different concentration thresholds for its variety of effects, and the required balance needed to achieve each has yet to be fully defined;

• Second, we must apply the approaches and methods of “-omics” (e.g., metabolomics and proteomics) and systems biology research in order to define the dynamic role of vitamins and their broad array of genomic, molecular, and biochemical interactions. Such work is necessary to understand the multiplicity of vitamin actions and to ultimately apply them directly at the level of the individual;

• Third, we must revise the concept of evidence-based nutrition, moving away from its current hierarchical system to recognizing in a comprehensive and integrated way the contributions of each type of approach to research. To adhere to the single gold standard of the randomized controlled trial ignores both how we have moved forward so productively over the last 100 years and the vital information that can be obtained from basic research and other human studies; further, it acts to stifle innovation in both scientific and regulatory affairs;

• Fourth, we must understand that changes in the supply and distribution of food during the next century are likely to be at least as dramatic as those that have occurred during this one. For example, inevitable environmental constraints will require that more food protein is derived from plant rather than animal sources, a shift that will directly impact dietary sources of vitamins.

In order to meet the challenge of achieving global health by 2112 among a population of 9 billion people, we must come up with new and creative ways in which those in academia, industry, and governmental and non-governmental organizations can work together to effectively manage these four changes.”

Based on: Blumberg J. Vitamins – Preparing for the Future. Symposium ‘100 years of vitamins – Past, present, future: Micronutrients – Macro impact’. November 2012. Basel, Switzerland.

1. Blumberg J. et al. Evidence-based criteria in the nutritional context. Nutrition Reviews. 2010; 68(8): 478-484.
2. Heaney R. P. et al. EBN ( Evidence-Based Nutrition) Ver. 2.0. Nutrition Today. 2011; 46(1):22-26.