Reexamination of a Meta-Analysis of the Effect of Antioxidant Supplementation on Mortality and Health in Randomized Trials

A recent meta-analysis of selected randomized clinical trials (RCTs), in which population groups of differing ages and health status were supplemented with various doses of β-carotene, vitamin A, and/or vitamin E, found that these interventions increased all-cause mortality. However, this meta-analysis did not consider the rationale of the constituent RCTs for antioxidant supplementation, none of which included mortality as a primary outcome. As the rationale for these trials was to test the hypothesis of a potential benefit of antioxidant supplementation, an alternative approach to a systematic evaluation of these RCTs would be to evaluate this outcome relative to the putative risk of greater total mortality. Thus, we examined these data based on the primary outcome of the 66 RCTs included in the meta-analysis via a decision analysis to identify whether the results provided a positive (i.e., benefit), null or negative (i.e., harm) outcome. Our evaluation indicated that of these RCTs, 24 had a positive outcome, 39 had a null outcome, and 3 had a negative outcome. We further categorized these interventions as primary (risk reduction in healthy populations) or secondary (slowing pathogenesis or preventing recurrent events and/or cause-specific mortality) prevention or therapeutic (treatment to improve quality of life, limit complications, and/or provide rehabilitation) studies, and determined positive outcomes in 8 of 20 primary prevention studies, 10 of 34 secondary prevention studies, and 6 out of 16 therapeutic studies. Seven of the eight RCTs with a positive outcome in primary prevention included participants in a population where malnutrition is frequently described. These results suggest that analyses of potential risks from antioxidant supplementation should be placed in the context of a benefit/risk ratio

Micronutrients in the life cycle: Requirements and sufficient supply

Macronutrients (fat, protein, carbohydrates) deliver energy and important material to ensure the entire body composition. Micronutrients are needed to keep this process of continuous construction and re-construction running. Consequently, the requirement for micronutrients will differ depending on the individual need which is related to the different metabolic conditions within the life cycle. Within the first 1000 days of life, from conception to the end of the second year of life the requirement for micronutrients is high and if the supply is inadequate that might have consequences for physical and at least cognitive development. In particular, iron, iodine, vitamin D and folate are micronutrients which might become critical during that period. Due to the fact that clinical symptoms of deficiencies develop late, but inadequate supply of one or more micronutrients may have consequences for health the term hidden hunger has been introduced to describe that situation. In particular the time period of pregnancy and early childhood is critical and hidden hunger is a worldwide problem, affecting >2 billion people, primarily females and children. The importance of different requirements during the life cycle is usually not considered. In addition, we do not really know what the individual requirement is. The estimation of the requirement is based on studies calculating the supply of a micronutrient to avoid a deficiency disease within a healthy population and is not based on sound scientific methodology or data. We need to consider that at different moments in the life cycle the supply might become critical in particular in case of a disease or sudden increase of metabolic turnover. In this narrative review we summarize data from studies dealing with different micronutrient requirements in pregnancy, exercise, vegan diet, adolescents and elderly. Knowledge of critical periods and related critical micronutrients might help to avoid hidden hunger and its consequences. Keywords: Micronutrients, Recommended dietary allowance (RDA), Life cycle, Sufficient supply, Safety, Deficienc