Chapter 24 Mineral Status Evaluation
Studies assessing the bioavailability of minerals in humans first appeared in the scientific literature in the 1960s,1–3 and over the ensuing years it became clear that minerals play an important role in the biochemistry of the human body.4,5 Abnormal levels of minerals can have deleterious effects on multiple enzyme systems, neuronal structures, and organs, including the brain, heart, thyroid, liver, kidneys, and skin.4 Thus, mineral analysis can be an important health assessment tool for many patients. Opinions vary considerably as to which tissue or body fluid may be “best” for the assessment of any or all nutritional element(s).
In general, nutritional elements are better evaluated in blood or in urine. Blood mineral status can be assessed from an intracellular (e.g., potassium in erythrocytes, zinc in leukocytes) or extracellular (e.g., copper in serum) perspective, or overall in whole blood (total cellular components and serum). Levels of elements in serum will vary day-to-day depending on dietary intake. Many factors, such as specific protein carriers and the ionic charge of an element and its capacity to be in equilibrium, may affect the usefulness and reproducibility of a specific assay method and the appropriateness of a chosen tissue. The life span of the cellular components of blood is about 3 to 4 months, so any analysis using these cellular components must be interpreted with this time frame in mind; reported values will reflect exposure and absorption that occurred during that period.
When mineral analyses involve the cellular components of blood, the clinician must ensure that samples are spun down immediately after collection, thereby separating the cells from the serum. If whole blood is allowed to sit for an extended period or is shipped without such separation, some of the cellular components will break down, allowing their contained elements to disperse into the liquid component of the sample. Subsequent centrifugation will remove all of the liquid component, leaving the remaining intact cells to be analyzed for their elements. In that scenario, erroneously low levels of intracellular elements would be reported.
Although hair analysis (see Chapter 17) does have the benefit of convenience and low cost, interpretation is made difficult by the ease with which hair can be contaminated from external sources of exposure. With that proviso, hair analysis can accurately reflect exposure to, and absorption of, a limited number of elements (e.g., chromium) or deficiencies of others (e.g., copper). The most appropriate use of hair analysis appears to be in the assessment of toxic metal exposure but even then, its utility remains highly controversial (“an unproven practice” according to the American Medical Association).6
Most clinicians employ whole blood or urine analysis in the evaluation of mineral status since these fluids are the simplest and most economical to collect and transport. Whole blood requires no centrifugation and, like urine, requires no special treatment, other than collection and shipping in approved containers. Red blood cell (RBC) analysis might best be utilized in the assessment of elements that are more commonly represented intracellularly (e.g., iron, potassium). Reputable laboratories use current technology (e.g., induction-coupled plasma mass spectroscopy) operated by highly trained personnel to perform these tests and to produce accurate and precise results. Excellent reference range data are available to allow appropriate interpretation of analytic findings.
Minerals and Disease
Serum levels of various minerals have been implicated as clinical markers of disease.4 Patients with cirrhosis have demonstrated low serum selenium,7 calcium,8 magnesium,9 and zinc.10 Those with emphysema and cancer have shown elevated serum copper concentrations; copper and manganese levels are often elevated in congestive heart failure, infection, and psychoses.11 Other associations have been observed between trace minerals and breast cancer,12 gastrointestinal malignancy,13 and malignant ascites,14 although in other studies, selenium, copper, zinc, and magnesium seemed to have no diagnostic value for distinguishing malignant from nonmalignant effusions15 or cervical cancer.16 Heart tissue levels of selenium, iron, copper, zinc, and phosphorus have been associated with ejection fraction and cardiac index.17 In men infected with human immunodeficiency virus, helper T-type 4 cells seemed closely correlated with serum magnesium concentration.18
The ratios of trace elements may be indicators for various disease states. The concentrations of copper, zinc, and selenium, and their relative levels in whole blood and thyroid tissue, follow specific patterns for various thyroid disorders, including thyroid cancer. Further, and although the mechanisms are unclear, the copper-to-zinc ratio was found to be significantly increased in patients with breast cancer but not in patients with benign breast diseases.19 In one study, serum copper-to-zinc ratios were shown to be of diagnostic and prognostic value in head, face, and neck cancer, with alterations in copper, zinc, and copper-to-zinc ratio related to the stage of the disease.20 Other studies identified distinct differences in copper/zinc ratios among various levels of skin disease severity.21
There are a number of minerals that are common to all living organisms, in that they support biochemical processes in structural and functional roles. These essential elements are calcium, chloride, copper, iodine, iron, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, sodium, and zinc (and perhaps, boron, cobalt, nickel, and sulfur). Other minerals, although not discussed here, have also been described as “essential,” including chromium,22 fluoride,23 and vanadium.24
Dietary sources of calcium include dairy products, canned fish with bones (e.g., salmon, sardines), green leafy vegetables, nuts, and seeds. Assessment of dietary intake of calcium is confounded by multiple factors that affect absorption, such as the quantity of fiber and other natural chelators in the diet; gastric acidity; the ratio of dietary calcium to phosphorus (and dietary magnesium); as well as gut transit time and other factors.
Serum calcium is so closely regulated (by the parathyroid gland) that its use as an indicator of calcium balance is not reliable when considered in isolation. Measurement of ionized calcium may be useful in evaluation of calcium status. Urinary calcium is of value in a patient with a known low total calcium intake and persistent calciuria. Hair calcium levels are subject to considerable variability and should not be taken as a quantitative determination of calcium status (although a relationship between hair calcium level and coronary disease has been reported).25,26 In patients with high phosphorus and low calcium intakes, hair calcium level was consistently reported as much as three times higher than normal. Hair calcium returned to normal with proper supplementation and dietary changes.27
In one study that evaluated intracellular, plasma, and membranous levels of calcium and magnesium in hypertensive patients, there were no differences between controls and patients. However, the absolute levels of calcium and magnesium were lower, and the calcium/magnesium ratio in membranes was significantly higher in patients with essential hypertension than in healthy subjects.28
The best test to evaluate body calcium sufficiency may well be whole blood analysis, since this will assess calcium present in serum, intracellularly, and in the cell membranes.
Chloride is necessary for the production of hydrochloric acid in the stomach and is also essential in cellular pump functions. The main dietary source of chloride is table salt. Chloride is readily assessed in serum and in urine.
Increased serum chloride may be associated with dehydration but could be present with either a metabolic acidosis or a respiratory alkalosis. High chloride can also be present along with elevated sodium in conditions such as Cushing disease. Urine chloride analysis, and often the analysis of urine sodium as well, may be important when considering alkalosis or acidosis or when assessing high or low serum chloride levels. Low serum chloride accompanies low serum sodium; low chloride may be associated with metabolic alkalosis and is often seen with prolonged emesis or in conditions causing respiratory acidosis, such as chronic obstructive pulmonary disease.
Body chloride levels are best evaluated in serum along with other electrolytes such as sodium. Urine chloride is a necessary component of a full electrolyte assessment and/or a metabolic panel.
Cobalt is essential in the production of vitamin B12, which is synthesized by bacteria. Cobalt metabolism and testing is better discussed elsewhere, especially in the context of vitamin B12 deficiency.
Under normal conditions, far more copper is absorbed than is needed by the body. Dietary sources include beans, eggs, fish, fresh fruits, liver, milk, mushrooms, nuts, oysters, peas, poultry, and whole grains. Nearly all dietary copper is stored initially in the liver, leaving only a small percentage in the blood. The principal mechanism for the control of copper homeostasis is excretion through the biliary system.
Because 95% of copper in serum is bound to the protein ceruloplasmin, there is almost no ionic copper so urinary copper output usually is minimal. At present, analysis of copper in serum may be the best indicator of body copper levels, provided that clinical conditions known to cause abnormal copper metabolism (e.g., Wilson’s disease, cirrhosis of the liver) have been ruled out.27 Some studies have shown hair copper measurement to be an acceptable method of assessing copper status29,30 with the same provisos as mentioned previously regarding the ruling out of other illnesses known to affect copper metabolism and retention. When high copper levels are seen on hair analysis, external copper contamination (e.g., exposure to swimming pool and hot tub water, which are often disinfected with copper-containing chemicals) always should be considered.
Iodine is necessary for the synthesis of thyroid hormones; iodine deficiency may lead to enlargement of the thyroid gland (goiter). Although iodine is readily measurable in urine, levels are highly variable31; thus, evaluation of urine iodine is not a reliable method to assess body iodine status. In contrast, it has been suggested that whole body sufficiency of iodine may be assessed in urine using an “iodine loading test.”32 Interpretation of the results of this test presupposes specific receptor/storage sites that take up and store iodine/iodide. When body storage of iodine/iodide is optimal, the percentage excretion of an oral loading dose of iodine/iodide excreted in urine is maximal; some authors purport that body stores are optimal when excretion is 90% or more.33 An emerging assessment of iodine status is serum thyroglobulin, which appears to be a better measure of iodine status over weeks and months.34