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Vitamins and Trace Elements: The Distances between Deficiency and Repletion and between Care and Prevention

Deficiency in micronutrients is a predominant problem of public health in the world. Iodine, vitamin A and iron are the micronutrients with the highest prevalence of deficiency, followed by zinc , folic acid and possibly vitamin B12 and vitamin D. Requirement and dietary allowance of micronutrients have been recently revised in Europe and North America (1). This revision is mainly based on epidemiological data (2). However, the biomarkers used for evaluating the nutritional status in micronutrients lack sensitivity and specificity, especially in the case of fat-soluble vitamins (3). The assay in blood of metabolic factors, the level of which depends on the cellular content in coenzymes, is an interesting approach which can be performed by mass spectrometry in specialized laboratories. This is the case for deficiencies in folate, vitamin B6, vitamin B12 and vitamin B2, using markers such as homocysteine, methylmalonate and cystathionine. However, the activity of the target enzymes depends also on genetic polymorphisms which influence the requirements for the corresponding vitamins. This illustrates the need to take into account the distribution of genetic determinants in a population to estimate better the dietary allowance of the related vitamins. In this issue, an example is given by Adjalla et al. who estimated the mutated allele frequencies of methylenetetrahydrofolate reductase 677 C→T, 1298 A→C and methionine synthase 2756 A→G polymorphisms in genomic DNA, in two populations from Benin and Togo. These polymorphisms are genetic determinants of folate and homocysteine metabolism (4). Knowledge is also lacking not only about revision of the tables of micronutrient contents of food but also about bioavailability and the factors interfering with this bioavailability. In this issue, Borel has reviewed the factors influencing intestinal absorption of fat-soluble vitamins and related biofactors. A clinical deficiency is rarely limited to symptoms related to a single vitamin, such as Addisson-Biermer disease and vitamin B12 deficiency. It results rather from a global malabsorption or malnutrition. However, vitamins may be implicated in the occurrence or evolution of multi-factorial diseases, in the absence of clinically established deficiency. For two decades, the association of the cellular status of vitamins and trace elements with degenerative diseases, such as cardiovascular and neurodegenerative diseases, malformation (neural tube defects), genetic diseases (Down’s syndrome) and cancer has been hypothesized from experimental data, using cell biology and animal models (5–8). Case-control and follow-up studies seem to confirm a number of these hypotheses. One example is the relationship between folate, vitamin B12, homocysteine and DNA methylation in digestive cancer, one topic discussed in the article of Brunaud et al. Cellular oxidant stress is a key pathomechanism of degenerative diseases which is influenced by fat-soluble anti-oxidant vitamins, vitamin C and trace elements and also by metabolites such as homocysteine, the cellular level of which is influenced by folate, vitamin B12, vitamin B6 and vitamin B2. This complexity of nutrient interactions explains the difficulty in defining an antioxidant supplementation with several micronutrients to prevent the development of degenerative diseases. These anti-oxidant micronutrients have been also evaluated as actors or therapeutic agents for preventing the development of type 2 diabetes mellitus (9). This issue is dealt with in a Review by Faure. Vitamins and trace elements also influence immunity, as shown for selenium in the study of Safir et al. This explains the interest in evaluating the link between micronutrient deficiencies and infectious diseases (10). The therapeutic interest in trace elements, particularly in selenium, has been also evidenced in experimental studies on animals. This is the case for the treatment of parasitic diseases, such as Trypanonosoma cruzi infection, by an interaction with innate immunity and acute inflammatory response, as discussed in this issue by Rivera et al. Finally, there is a growing number of experimental and epidemiological evidence for a link between vitamin and trace element status and public health problems such as degenerative diseases and cancer, in which the distance between deficiency and repletion has to be defined, as well as the evaluation of benefits and side effects of supplementation and fortified food (11, 12). In this context, a better knowledge of the relationship between the type of diet, i.e., the Mediterranean diet as reviewed in this issue by Gerber, and disease prevalence in populations will help to orientate investigation toward the complex cause/consequence relationship between and nutrition and pathology, and nutrition and genetics.