Laboratory testing in nutritional medicine—part 1 - Nutritional Influences on Illness

Townsend Letter for Doctors and Patients, Dec, 2003 by Melvyn R. Werbach

Malnutrition

A number of laboratory studies have been used in the nutritional assessment of malnutrition; however, they are unlikely to uncover marginal malnutrition. Although plasma or serum albumin is a popular measure, sick patients may have low levels for several other reasons, such as inflammatory processes, gut losses due to gastrointestinal or cardiac disease, and renal losses due to kidney disease. Moreover, even when malnutrition is chronic, this measure is often normal because of compensatory mechanisms. Typical laboratory findings include serum albumin of less than 3.5 g/dL, serum prealbumin concentration less than 10 mg/dL, total lymphocyte count less than 1,200 mm3, and an anemia of chronic disease. (1)

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Hydrochloric Acid Deficiency

Since measuring gastric acidity directly by gastric intubation is uncomfortable for the patient, other methods have been devised. Analysis can be done using the Heidelberger pH capsule gastrointestinal radio transmitter or even with a simple, inexpensive gelatin capsule containing specially treated cotton floss*.

Even when it is absent in the fasting state, acid production following the entry of food is often normal; thus testing must be performed after the patient is given a potent parietal cell stimulus. (2)

Basal serum gastrin measurement may also be helpful, as somewhat increased levels can be found in conditions associated with achlorhydria if the antrum is not severely affected--such as atrophic gastritis and pernicious anemia. (3)

Specific Nutrient Abnormalities

Calcium

Ionized calcium measures unbound serum calcium. It is a useful measure of calcium balance when it is low; however, normal levels do not rule out a negative calcium balance. (4)

Hair calcium must be interpreted with caution, as a negative calcium balance may be accompanied by elevated hair levels. (This combination suggests that possibility of a nutritionally-induced secondary hyperparathyroidism related to a low calcium, high phosphorus diet.) (5) Moreover, grey hair is naturally lower in calcium. (6)

Chromium

Functional testing methods are currently the most dependable means of assessing chromium nutriture. If, for example, the diet can be strictly controlled for an adequate period of time, then improvement of impaired glucose tolerance in response to chromium supplementation will prove that chromium nutriture was deficient. (7) Functional testing can also be performed by examining the effect of glucose loading (usually 100 g) upon the serum chromium concentration. When chromium nutriture is deficient, serum chromium may drop one hour after the glucose load; thus, following chromium supplementation, a reduction in this response compared to baseline suggests improved chromium status. (8)

Since the majority of absorbed chromium is excreted in the urine, (9) urinary chromium is a reasonable measure of chromium absorption. Hair chromium may be of some value in indicating inadequate tissue chromium nutriture, (10) although it is believed to be unreliable except for severe deficiencies. (11) Neither serum chromium (12) nor whole blood chromium (13) is a useful measure of tissue stores.

Copper

Sensitive indicators of copper status include platelet copper (14) or total erythrocyte copper, (15) as well as the activity of erythrocyte superoxide dismutase, (16) or glutathione peroxidase, (14) or of platelet cytochrome c oxidase. (14)

Serum (17) and plasma (14) copper, as well as whole blood copper (18) and ceruloplasmin. (16) are not useful indicators of copper nutriture, and hair copper may be deceptive. (19)

When an increased body copper burden is suspected, as in Wilson's disease, a D-penicillamine challenge test will confirm the diagnosis. (20)

Fatty Acids

The measurement of fatty acids in the total phospholipid fraction of plasma and erythrocytes, while probably the most practical method of assessing fatty acid nutriture, suffers from the lack of long-term prospective studies of apparently healthy populations. Such studies would uncover sub-groups whose levels may be contributing to illnesses that only later will appear. (21)

Folic Acid

Severe folate deficiency is accompanied by a macrocytic anemia, although the size of erythrocytes may be entirely normal in lesser degrees of depletion. (22) Serum folate tends to reflect dietary intake over the past few weeks, while erythrocyte folate is much less sensitive to short-term variations in folate balance. (23) However, folate depletion in erythrocytes occurs only in the later stages of folic acid deficiency and is usually accompanied by megaloblastic anemia; thus patients with both acquired and inherited folate deficiency may remain moderately deficient for months or years, taking in just enough folate to prevent low red cell folate concentrations and frank anemia. (24) Therefore, both erythrocyte and serum folate studies should be performed.

Moreover, when evaluating for folate deficiency, serum vitamin B12 levels should be measured as, when both vitamins are low, deficiency of either may be primary. This is because megaloblastic intestinal cells may not absorb properly, causing a secondary deficiency of the other vitamin. (25) Moreover, a low erythrocyte folate level may occur in primary vitamin B12 deficiency, because vitamin B12 is necessary to keep methylfolate in red cells. (25)