Nutritional influences on illness

Townsend Letter for Doctors and Patients,  Jan, 2004  by Melvyn R. Werbach

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Laboratory Testing in Nutritional Medicine--Part 2

Selenium

The definitive test for selenium deficiency remains the response to selenium supplementation. (1) Of the available tests, blood glutathione peroxidase is one that has been shown to be a sensitive index of selenium nutriture. (2)

Hair selenium is also of value. It is correlated with selenium intake as well as with selenium concentrations in the liver, lung and renal cortex. However, the use of selenium-containing shampoos will falsely elevate hair selenium levels. (3)

Toenail selenium, while unaffected by dietary intake in the prior 3 months, is a reasonable measure of intake over the past 6 to 12 months. (4) Blood selenium is of limited usefulness as, while it responds quickly to dietary intake, (5) it tends to stay in the normal range except at the extremes of tissue selenium levels. (6) Urinary selenium, although inadequate as an indicator of tissue nutriture, may be useful to confirm the results of blood selenium testing. (7)

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Sodium

Serum sodium is commonly used as a measure of sodium nutriture. The principal cation of the extracellular fluid, any change in serum sodium is associated with a fluid shift into or out of the cell. Serum levels, however, do not reflect total body sodium content. (8)

Hair sodium does not reflect dietary intake or body stores. (9)

Thiamine

The most commonly used procedure for assessing thiamine nutriture has been the measurement of erythrocyte transketolase activity and its stimulation in vitro by the addition of thiamine pyrophosphate (the thiamine pyrophosphate effect). Because of the limitations of these two tests, (3) both should be performed together, along with an assessment of thiamine intake.

If available, the erythrocyte thiamine diphosphate level may be superior to the measurement of erythrocyte transketolase activity. (10)

Vitamin A

While low concentrations of plasma or serum retinol are suggestive of frank deficiency, more subtle tests are needed to identify the presence of a marginal deficiency. (3) Of these, the modified relative-dose-response test is proving to be highly reliable, while isotope dilution assay methods (which measure total body reserves) are currently being refined. (11)

Vitamin B6

Pyridoxal-5' phosphate (PLP) and pyridoxal (PL), its hydrolysis product and the ultimate transport form of B6, are the predominant vitamin B6 vitamers in the circulation; measurement of both (preferably in the erythrocytes rather than in the plasma) is recommended. (12) The urinary pyridoxic acid level may give additional information to that obtained from a combination of pyridoxal phosphate and pyridoxal plasma levels, for example during pregnancy when plasma pyridoxal phosphate is decreased while plasma pyridoxal is increased. (13)

The activities of enzymes that are vitamin B6-dependent (such as transminases) are of some value in assessing nutriture. However, they have a number of limitations. (3)

Xanthurenic acid and kynurenine excretion after a tryptophan load most likely represents an aberrant reaction to the load and has no documented clinical significance. In addition, pregnancy and contraceptive pills may render the test abnormal due to inhibition of kynureninase by estrogens. (14)

Vitamin B12

The diagnosis of vitamin B12 deficiency is often missed by routine laboratory tests, as many practitioners are unaware that the vitamin may be deficient despite normal serum vitamin B12 levels and the absence of a megaloblastic (large cell) anemia. (15) Moreover, serum vitamin B12 levels are often normal when cerebrospinal fluid vitamin B12 is deficient. (16) Most low serum cobalamin levels are not due to vitamin B12 deficiency but to gastric dysfunction in which protein-bound cobalamin is not digested; this can be corrected with oral administration of crystal cobalamin concentrate. (17)

One reason why serum, as well as intracellular vitamin B12 may be misleading, relates to the binding of the newly absorbed vitamin to transcobalamin II, a transport protein, to form holotranscobalamin II; thus this measure indicates the earliest stage of a negative B12 balance that is measurable from the serum. (18) In the elderly, a decline of this transport protein results in higher serum B12 levels but lower intracellular B12 levels; (17) therefore, although > 150 pmol/L is usually considered as normal, older individuals with serum vitamin B12 of 150-250 pmol/L may also have a tissue B12 deficiency. (19)

Another problem with serum vitamin B12 assays is that it is commonly done using radioisotope dilution techniques, resulting in values that may be falsely increased due to the presence of inactive cobalamin analogues. (20) The solution is to employ instead, a microbiological assay, since the microorganism whose growth is measured following feeding of the patient's serum, will be unaffected by the inactive analogues. (21)

If patients have hematological, neuropsychiatric or gastrointestional disorders suggestive of cobalamin deficiency even though their serum cobalamin levels are normal, intracellular cobalamin deficiency can be diagnosed by testing for elevated serum methylmalonic acid and homocysteine levels. (22) The serum methylmalonic acid assay appears especially useful in evaluating vitamin B12 status in hepatic disease as serum vitamin B12 may be increased. (23)