Drug-Nutrient Interactions: Do We Want to Rely upon Nutrition or Drugs?
Anthea Webb, WFP Indonesia Country Director, is quoted in the United Nations Global Nutrition Agenda (UNGNA v1.0), “As we come to grips with the double burden of under- and over nutrition, empowering people to choose a healthy, balanced diet becomes even more urgent. The UN Global Nutrition Agenda will be judged by how it helps ease that burden.”
As someone trained in nutrition, I accept the premise that nutritional status affects disease risk. I especially believe in the 6th core principle underlying the UN’s interagency work on nutrition – Good nutrition is necessary for functioning education systems, social protection, and efforts to eradicate poverty and reduce inequality. As our CEO of DSM, Feike Sijbesma, has said, “You cannot be successful, nor call yourself successful, in a society that fails.”
Why then do so many recent randomized controlled trials (RCTs) fail to show a benefit from nutritional supplementation? One reason is the tendency to conduct secondary analyses on RCTs; in other words mining for secondary associations other than those proposed in the original RCT.
Some may argue RCTs fail to show benefit because dietary supplements are a poor substitute for whole foods. This is not accurate. Vitamin D fortification of orange juice is as effective as oral supplements in maintaining vitamin D status (although vitamin D2 is not equivalent to D3). Red blood cell docosahexaenoic acid (DHA) concentration increase in a dose-dependent, linear fashion regardless of whether individuals consume DHA-fortified snack bars or dietary supplements. Dietary supplements, like foods, can be an important source of nutrition.
There is an alternative explanation. Increasingly, concurrent use of pharmaceuticals may confound the the results of nutrition RCTs. Approximately 45% of the AREDS2 individuals were following statin and aspirin therapy. Statins are known to alter serum n-3:n-6 ratios, predictably increasing the dietary DHA requirement to maintain RBC DHA concentrations.
Blackwood and colleagues now report that statin therapy (ezetimibe) inhibits the absorption of omega-3 fatty acids. These findings provide perspective on the 2012 meta-analysis by Rizos et al. As the use of statins (and other medications) has increased in RCTs examining the health effects of n-3 fatty acids, the apparent efficacy of n-3 interventions has been reduced. Could statin drugs be negating the benefits of increasing omega-3 fatty acid intake?
Research seems to be providing insight. Drugs can affect disease outcomes but they also impact nutritional status. Should nutrition or disease be our first choice in managing disease risk and health outcomes? What is your preference?
Blackwood DP, LaVallee RK, Busaidi AA, Jassal DS, Pierce GN. A randomized trial of the effects of ezetimibe on the absorption of omega-3 fatty acids in cardiac disease patients: A pilot study. 2015 Clin Nutr ESPEN doi: 10.1016/j.clsnesp.2015.07.002
Biancuzzo RM, Young A, Bibuild D, Cai MH, Winter MR, Klein EK, Ameri A, Reitz R, Salameh W, Chen TC, Holick MF. Fortification of orange juice with vitamin D2 or vitamin D3 is as effective as an oral supplement in maintaining vitamin D status in adults. 2010 Am J Clin Nutr doi: 10.3945/ajcn.2009.27972
Arterburn LM, Oken HA, Hoffman JP, Bailey-Hall E, Chung G, Rom D, Hamersley J, McCarthy D. Bioequivalence of docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food. 2007 Lipids doi: 10.1007/s11745-007-3098-5
Chew EY, Clemons TE, Agron E, Launer LJ, Grodstein F, Bernstein PS, for the Age-Related Eye Disease Study 2 (AREDS2). Effect of omega-3 fatty acids, lutein/zeaxanthin, or other nutrient supplementation on cognitive function: the AREDS2 randomized clinical trial. 2015 JAMA doi: 10.1001/jama.2015.9677
Nozue T, Michishita I. Statin treatment alters serum n-3 to n-6 polyunsaturated fatty acid ratio in patients with dyslipidemia. 2015 Lipids Health Dis doi: 10.1186/s12944-015-0066-6
Rizos EC, Ntzani EE, Bika E, Kostapanos MA, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular events: a systematic review and meta-analysis. 2012 JAMA doi: 10.1001/2012.jama.11374