Much of the work performed to determine the normal range of plasma micronutrients was undertaken in healthy subjects. This information was obtained from depletion studies of single nutrients, and has been used to compile many of the nutritional guides for professionals that are still in circulation today. However, the relevance of these studies have been questioned with regard diseased individuals1. Evidence suggests that the presence of disease can alter the plasma levels of micronutrients, irrespective of dietary intake. The acceptance that plasma levels of micronutrients can be changed during particular disease states suggests that diet may not be an important factor when an apparent association with circulating levels is found. Association between disease and plasma micronutrient levels are often used as evidence that dietary deficiencies of particular nutrients cause the development of particular diseases. However, care should be exercised in attributing cause and effect.
Plasma vitamin C levels have been shown to fall in severe infection, which suggests that plasma concentrations of vitamin C are not related to dietary intake. Trauma is known to reduce the vitamin C content of lymphocytes, and cold symptoms too have been shown to correlate with a fall in the plasma levels of vitamin C. The reason for this fall in vitamin C may be the production of new neutrophils that take up the vitamin C, presumably to increase antioxidant defences or to transport the vitamin to areas of tissue infection that require higher concentrations. However, interestingly, during times of infection free iron concentration increase due to a reduction in the transferrin transport protein (and other plasma proteins). Because vitamin C is a pro-oxidant in the presence of iron, the uptake of vitamin C by neutrophils may therefore reduce the chance of oxidation in the plasma.
Plasma retinol levels can also be affected by disease. Circulating levels of retinol show disconnection from dietary intake, with the exception of when plasma levels falls below 0.7µmol/L. During a measles infection for example, retinol levels drop, but return to normal following the end of the infection. Plasma levels of retinol are dependent of the circulating levels of retinol-binding protein, which can fall during infection due to urinary losses (due to increased endothelial permeability). This can cause a fall in plasma retinol with excretion being equal to about half of the retinol daily recommended level. Vitamin E is also transported by plasma proteins, and so severe infections (such as malaria) that increase endothelial permeability can also decrease circulating vitamin E. Based on the inverse association between cardiovascular disease and vitamin E, it is tempting to speculate that sub-clinical illness causes increased endothelial permeability, a subsequent reduction in plasma proteins, and a fall in vitamin E.
Researchers2 have investigated the association between the systemic inflammation in 1303 patients as measured by plasma C-reactive protein levels, and plasma micronutrient concentrations from blood taken during routine screening. Plasma levels of zinc, copper, selenium, vitamin A, vitamin B6, vitamin C and vitamin D were all found to decrease with increasing severity of systemic inflammation. The most sensitive micronutrient changes were detected for vitamin C, vitamin B6 and selenium, which were reduced with only small increases in C-reactive protein (increases of only 5 to 10mg/mL were required to show lower levels of these micronutrients). The authors also noted large variations in the micronutrient reductions between patients suggesting a large natural biological variation in this effect. For vitamin C, selenium, vitamin B6 and vitamin D, the reduction in plasma concentration with increasing inflammation was in the order to 40%. Illness may therefore cause substantial falls in some micronutrients.
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