Bioavailability of dietary supplements
The Pharmaceutical Journal Vol 264 No 7084p304-305
February 19, 2000 Forum
National Institutes of Health/American Society for Nutritional Sciences
Bioavailability of dietary supplements
The use of dietary supplements is increasing rapidly, but knowledge of the factors that influence the safety and efficacy of these products has not kept pace with public demand. One of these factors is bioavailability. A two-day international conference to consider this issue was organised by the US Office of Dietary Supplements (ODS) of the National Institutes of Health (NIH) in collaboration with the Life Sciences Research Office (LSRO) of the American Society for Nutritional Sciences (ASNS). Held at the NIH campus in Bethesda, Maryland, US, on January 5-6, 2000, it attracted more than 250 participants, mainly from academia and industry. Pamela Mason reports
Reflecting on the growing understanding of the importance of nutrition in the prevention of chronic disease, Professor MARY FRANCES PICCIANO (department of nutrition, Pennsylvania State University and visiting nutrition scientist, ODS) highlighted the increased use of dietary supplements throughout the western world. Many individuals viewed these products as an important component of a healthy lifestyle, but scientific knowledge of their efficacy and safety was limited, with the result that health professionals had little rigorous evidence on which to base recommendations and advice to the public.
Natcher building, NIH campus, Bethesda, Maryland, venue for the conference
Definitions and concepts
One of the problems with bioavailability discussed at the conference is that there is no consensus as to how it should be defined. Indeed, several speakers provided different definitions, some regarding bioavailability simply as the proportion of a nutrient or bioactive ingredient that was absorbed from the gastrointestinal tract, while others included metabolism, excretion, utilisation and a measure of efficacy in their definitions. Comparisons were frequently made with the concept of drug bioavailability which emphasises the rate at which a drug reached its target organ or body system where it produced the desired effect.
Traditionally, the most important consideration relating to nutrient bioavailability has been the attainment of an adequate nutritional status. However, the conference was told that supplements containing vitamins and minerals, as well as those containing other bioactive ingredients (eg, garlic, Gingko biloba, isoflavones, echinacea) were being used by consumers for effects other than adequate nutrition. Such effects included lipid lowering, memory enhancement and treatment of depression ?effects, which, if proven, were pharmacological rather than nutritional.
This means that the bioavailability of ingredients in dietary supplements should probably include a measure of efficacy, although there was general agreement at the meeting that bioavailability might need to be defined differently for each ingredient. Concepts related to drug bioavailability might be useful in some cases.
The bioavailability of a drug is often characterised by its plasma concentration, and this measure could be applied to the active ingredients of some herbal products, vitamins and minerals, the meeting was told. However, for a mineral such as calcium, measurement of plasma concentration does not give an adequate indication of bioavailability. This is because plasma calcium concentration is tightly controlled, even when calcium status (ie, the amount of calcium in the body) changes.
In elderly people, plasma levels of fat- soluble vitamins can be misleading. This is because chylomicron clearance is delayed in the elderly, and this can result in, for example, raised plasma levels of vitamin A, which does not necessarily reflect increased bioavailability.
In addition to age, an important determinant of bioavailability is physiological status such as pregnancy. According to Professor JANET KING (director, Western Human Nutrition Research Center, University of California), nutrient needs increased during pregnancy but were often met by homeostatic adjustments such as increased absorption and renal conversion. However, these homeostatic mechanisms varied for different nutrients and rigorous studies were required to determine the potential benefits of supplements during both pregnancy and lactation.
But why was bioavailability thought to be so important and why was it being considered at this particular time? Dr ELIZABETH YETLEY (director, office of special nutritionals, Food and Drug Administration) pointed out that under the US Dietary Supplement and Health Education Act (DSHEA), dietary supplements were regulated as foods. (A similar situation also exists in the UK where supplements are regulated as foods rather than as medicines.)
The regulatory framework for foods was not as rigorous as it was for medicines so bioavailability of supplements had often been overlooked. But with the increasing - and relatively uncontrolled - use of these products, issues of safety and efficacy were raising awareness of the need to look at bioavailability. Thus, if two products claimed to have the same ingredients in the same quantities, but had different bioavailabilities (because of, say, formulation differences) both safety and efficacy could be affected. On one hand, high bioavailability was not always beneficial, simply because it could result in toxicity, but, on the other, low bioavailability could result in a supplement that did not have the intended effect.
Bioavailability also had implications for the cost of an effective dose of a supplement to the consumer, Dr JOHN HATHCOCK (vice president, Council for Responsible Nutrition) said. For example, in the US, the cost of a 30-day supply of a calcium supplement (providing 1,000mg of calcium a day) varied from $1.90 for calcium carbonate and $4.62 for calcium lactate to $12.95 for calcium gluconate, and calcium carbonate was, generally considered to be the most bioavailable source.
Lack of data
Dr ALLISON YATES (director, Food and Nutrition Board, US National Academy of Sciences) acknowledged the relative lack of biovailability data for dietary supplements. For example, the bioavailability of folate from food was often quoted as being half that of folic acid from supplements, but more work was required to be certain that this really was the case.
The biovailability of iron was known to vary, depending on the type of food and diet consumed. Although a plant-based diet might contain as much, if not more, iron than an omniverous diet, the bioavailability of iron from plant foods was considerably less than that from animal produce. Some US studies had shown that up to 98 per cent of vegetarian women had inadequate iron status compared with only 25 per cent of omniverous women. This pointed to the importance of bioavailability in looking at nutritional requirements for people consuming different types of diets.
Bioavailability data were needed to set dietary standards (eg, Dietary Reference Values, Recommended Daily Amounts), Dr Yates continued. For example, recommendations for vitamin B12 intakes were based on the assumption that 50 per cent of the vitamin was absorbed from food and that gastric, pancreatic and ileal function were normal - assumptions which were not necessarily valid in older people, many of whom had atrophic gastritis. For those over the age of 50, supplements and/or fortified foods might be needed to meet the vitamin B12 requirement.
Labelling and standardisation
Bioavailability also has implications for labelling of products, the meeting was told. The content declared on the label - even if accurate - does not necessarily give an indication of bioavailability. According to Professor ROBERT HEANEY (John A. Creighton Professor, Creighton University, Nebraska, US), the bioavailability of active ingredients depended on the presence of "enhancers" (eg, vitamin C with iron) and "inhibitors" (eg, iron with zinc and vice versa). These could be present both in the supplement and the diet. Interactions with drugs would also have an influence. Bioavailability would depend on the nutritional and physiological status of the individual, and although it would be useful to have such detailed data, this was not currently practical because measuring bioavailability in individuals was expensive and time consuming. Bioavailability therefore had to be determined on the basis of the product, not the individual.
Dr V. SCRINI SRINIVASAN (director, dietary supplements division, US Pharmacopeia) highlighted the fact that the US Pharmacopeia had developed disintegration and dissolution standards for vitamins and minerals (PJ 1999;263:611). Acknowledging that the USP dissolution tests were a "good step forward", Professor HEANEY argued that solubility, and hence dissolution, tests were not always appropriate measures of bioavailability. Disintegration tests were vital, but in the complex environment of the gut, a dissolution test might not be meaningful. Moreover, the most soluble calcium salts (eg, calcium citrate) were less bioavailable than the relatively insoluble ones (eg, calcium carbonate). Formulation had a more significant impact on bioavailability of calcium than solubility.
For botanicals such as echinacea, Gingko biloba and isoflavones, the source of the plant material could affect bioavailability and there was a clear need for standardised materials. Professor KENNETH SETCHELL (professor of pediatrics, Childrens' Hospital Medical Center, Cincinnati) illustrated this by discussing isoflavones, ingredients which are increasingly promoted for menopausal symptoms and prevention of cancer and cardiovascular disease. High performance liquid chromatography (HPLC) analysis of several products taken from pharmacy and health food stores in the US had demonstrated significant variations in concentrations of active ingredients, with some containing almost nothing despite label claims to the contrary.
In her conference summary, Professor PICCIANO recognised that bioavailability was defined in many different ways and that no single definition was appropriate for every ingredient. However, bioavailability was crucial because it had implications for safety, efficacy and cost of dietary supplements. When advising consumers, there was a need to admit limitations in the research data and the difficulty of providing evidence-based information.
In relation to herbal products, there was a need to identify which were the active ingredients. For example, hypericin had been assumed to be the main active ingredient in St John's Wort, but this was no longer certain. Traditionally, herbalists had talked in terms of the importance of the whole plant, but when putting extracts into tablets and capsules, there was a need to know which ingredients were potentially efficacious, whether they interacted with each other and whether they were bioavailable.
Standardised reference material should be made available, in particular so that results from studies could be properly compared. Early studies with garlic, for example, had shown inconsistent results, partly because some researchers used water soluble material, while others used oil soluble material.
Herbal products were complex, and numerous variables could influence their efficacy. Therefore, study conditions should always be carefully specified.
Citation: The Pharmaceutical Journal URI: 20000531
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