Recommendations for micronutrient intakes are based on the assumption that there are daily amounts that meet the average needs of almost all healthy populations of the same age and sex living under similar circumstances. The example of vitamin C, however, has shown that these estimates are not universally valid. The outcomes of several studies which recorded varying intakes and plasma concentrations of vitamin C were pooled in a meta-analysis (1). Based on the data the average intakes and the range (deviations) needed to achieve an estimated optimal vitamin C concentration of 50 μmol/L (2) was calculated. On average, the calculated intake for adults was 100 mg per day, which corresponds approximately to the recommendations of most European nutrition organizations (e.g., 3) and the US Food and Nutrition Board (4). The variation did not follow a normal distribution curve, but showed a bias toward higher intakes, which indicates that there are segments of the population who need to consume larger amounts of vitamin C to reach the recommended plasma concentration of 50 μmol/L. This concurs with studies which suggested a recommended intake of up to 150 mg per day for healthy adults (2).
Moreover, there are increasing indications that certain population groups have genetic variations (polymorphisms) that influence their micronutrient status and, hence, their intake requirements. Recent research with female volunteers showed that almost 50 percent of the population has a genetic variation that reduces their ability to produce sufficient amounts of vitamin A from beta-carotene. Studies have shown that younger women who carry this genetic variation are especially at risk: they have a tendency to consume too little vitamin A rich food and are therefore very dependent on the beta-carotene form of the nutrient (5). As part of a recent study blood samples from over 15,000 women were analyzed and a polymorphism was found in a gene that encodes a transport protein responsible for the uptake of vitamin C in the intestine (6). The genetic variant was associated with low concentrations of ascorbic acid in the blood, which is possibly linked to restricted transport function. It is not yet clear whether this polymorphism increases the risk of an inadequate supply of vitamin C and associated diseases (7).
The following example shows how such genetic variants can influence study outcomes and their interpretation: in neither the HOPE Study nor its follow-up, HOPE-TOO, did results in the form of the average values for all participants indicate an association between the daily intake of 400 IU vitamin E and a reduced risk of suffering from heart and vascular diseases (heart attack, stroke, heart failure, etc.) (8). However, closer analysis of the data obtained from these studies showed that some patients had benefited greatly from supplementation with vitamin E: these were type 2 diabetics who carry a particular genetic variant of the hemoglobin transporter “haptoglobin” (Hp). This genotype (Hp 2-2) is characterized by haptoglobin with comparatively modest antioxidant activity.Cardiovascular disease deaths and non-fatal myocardial infarctions were markedly rarer in type 2 diabetics who were HP 2-2 carriers and consumed supplemental vitamin E (9). Evidently diabetics with this genotype have an increased requirement for antioxidant micronutrients and were able to derive health benefits from the targeted consumption of vitamin E. A more recent study with subjects suffering from type 2 diabetes and carrying Hp 2-2 confirmed this observation: the risk of cardiovascular illness among participants who took vitamin E was substantially lower (10). The effect was so striking that it led to early termination of the study: it would not have been ethical to stop the placebo group taking the vitamin E preparations. It is estimated that the frequency of the Hp 2-2 genotype in western populations is around 36 percent.
These and other factors should be taken into consideration when planning future intervention studies and developing intake recommendations for the prevention of cardiovascular and other diseases.