Introduction

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

Essential Minerals

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