One is okay, more is better? Pharmacological aspects and safe limits of nutritional supplements

Abstract

The use of vitamins, minerals and other supplements has increased considerably during recent years. In the National Diet and Nutrition Survey of British adults aged 19-64 years 40 % of those surveyed were taking supplements. In 2005 sales of dietary supplements in the UK were approximately £325 . 7 · 10 6 in 'bricks and mortar' shops (excluding health food shops). The physiological effects of vitamins and minerals in amounts approximating to the UK reference nutrient intake or the EU RDA are well understood in terms of reducing the risk of micronutrient deficiency. However, the effects of vitamins, minerals and other supplements in larger amounts have attracted much attention in recent decades, and these effects, some of which may be pharmacological, are not as well categorised. Some of these effects are beneficial, some are not. Although vitamins and minerals and other supplements are generally safe at higher doses, there are some safety issues that are relevant in the context of the wide availability of supplements without a doctor's prescription. Thus, several authorities throughout the world have established upper limits (UL) for the intake of vitamins and minerals, and the EU is in the process of setting maximum permitted levels (MPL) for vitamins and minerals in food supplements. The present paper discusses the potential benefits and safety issues relating to the use of supplements at doses higher than the RDA. The rationale for the establishment of UL is also discussed, explaining the differences between the values set by different authorities and the expected guidance and legislation from the European Commission on MPL for vitamins and minerals in food supplements.

The Prevalence of Micronutrient Deficiencies and Inadequacies in the Middle East and Approaches to Interventions

“…Risk assessment models used to derive tolerable upper intake levels, safe upper levels, or guidance levels for vitamins and minerals have been established by advisory or regulatory authorities in Australia, Europe, New Zealand, United Kingdom, and the USA [134]. As it is unethical and infeasible to conduct clinical trials targeted at adverse outcomes, these values are based on harm observed in animal model studies and/or available case reports of clinical evidence of toxicity.…”

The balance between food and dietary supplements in the general population

“…Adapted and combined from Refs. (40,83,109) . LRNI, lower reference nutrient intake; EAR, estimated average requirement; RNI, reference nutrient intake; SUL, safe upper level.…”

Oxidative Stress and Inflammation in Heart Disease: Do Antioxidants Have a Role in Treatment and/or Prevention?

“…Safety is the overarching issue in drug development today, but little was done historically to determine if the antioxidant being tested for an inflammatory-mediated cardiovascular manifestation is safely tolerated at the levels required to provide therapeutic relief [71, 72]. Since the high standards of chemistry, manufacturing, and controls (CMC) required for pharmaceutical drugs are unlikely to be applied to nutraceutical or dietary-supplement-type products, many of the questions regarding safety and efficacy of antioxidants will most likely be answered in the future related to the development of proprietary prodrugs seeking regulatory approval.…”