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Magnesium and Zinc: Is Erythrocyte Testing Useful?


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September 2012

A recent review of Mayo Medical Laboratories test requests revealed an increase in orders for erythrocyte magnesium (Mg-RBC) and erythrocyte zinc (Zn-RBC). Discussions with health care providers ordering these tests indicate that Mg-RBC is used almost solely to assess nutritional status in diabetic patients. Use of Zn-RBC determinations to differentiate transient from permanent hypothyroidism has been described in the literature, although it is also possible that testing is being done to assess nutritional levels. Since Mayo Medical Laboratories offers the serum test for zinc  and magnesium, we investigated the utility of red blood cell testing.


Zinc is an essential element and is required for active wound healing and also has a role in thyroid homeostasis. Along with cysteine compounds, zinc is involved in the synthesis of thyroid hormones. Some research shows that zinc deficiency correlates with short-term decreased triiodothyronine (T3) and thyroxine (T4) levels1 Zinc depletion occurs either because it is not absorbed from the diet or it is lost after absorption. Dietary deficiency may be due to absence (total parenteral nutrition) or because the zinc in the diet is bound to fiber and not available for absorption. Excess copper and iron in the diet  (eg, iron supplements) interfere with zinc uptake. The 2 most common routes of loss are 1) exudates from open wounds (eg, burn patients who lose zinc in the exudates from burn sites) and 2) gastrointestinal loss. Hepatic cirrhosis causes loss of zinc by enhancing renal excretion. Other diseases that cause low serum zinc are ulcerative colitis, Crohn disease, regional enteritis, sprue, intestinal bypass, neoplastic disease, and increased catabolism induced by anabolic steroids. The conditions of anorexia and starvation also result in low zinc levels. Increased loss of zinc by frequent urination appears to contribute to the marginal zinc nutritional status that has been observed in diabetics.

Measurement of zinc can be performed in plasma or serum, red blood cells, neutrophils, lymphocytes, and hair. Measurement of zinc in the plasma or serum is simple, readily available, and is useful if the specimen is not hemolyzed and other conditions (eg, infections, acute stress, myocardial infarction, and intravascular hemolysis) are ruled out. Hair and red blood cell turnover is slow; thus, the zinc levels in these specimen types do not reflect recent changes with respect to zinc status2.

One peer-reviewed publication addresses the clinical use of Zn-RBC. The 2011 paper by Kuriyama and colleagues indicates that zinc levels in red blood cells can differentiate transient hypothyroidism from permanent hypothyroidism.1A careful read of the paper indicates only marginal differentiation. The Mayo Clinic Endocrinology Thyroid Group advises that there are better methods to differentiate the 2 disorders. Mayo Medical Laboratories offers testing (TAB/82041 Thyroid Autoantibodies Profile, Serum)  to predict the long-term probability of hypothyroidism. Stefan Grebe, MD, director of the endocrine laboratory at Mayo Clinic in Rochester, Minnesota, provides information regarding transient hypothyroidism. (see sidebar)


Magnesium, along with potassium, is a major intracellular cation. Approximately 70% of magnesium ions are stored in bone. The remainder is involved in intermediary metabolic processes; about 70% is present in free form, while the other 30% is bound to proteins (especially albumin), citrates, phosphate, and other complex formers. The serum magnesium level is kept constant within very narrow limits. Regulation takes place mainly via the kidneys, primarily the ascending loop of Henle.

Magnesium testing may be ordered to assess a deficiency as part of an evaluation of malabsorption, malnutrition, diarrhea, or alcoholism. Magnesium levels may also be monitored in patients with a kidney disorder or uncontrolled diabetes, along with kidney function tests such as a BUN and creatinine, to monitor kidney function and make sure that the person is not excreting or retaining excessive amounts of magnesium.

Only 2 peer-reviewed papers in the medical literature address the clinical use of Mg-RBC3,4. A 2011 paper  by Sales and colleagues concludes that serum Mg  (Mg-S) provides fundamentally the same information as Mg-RBC regarding the involvement of Mg in control of glucose. The authors provide considerable insight regarding the effect of Mg-S on glucose, but only mention Mg-RBC as an alternative. Mg-RBC provides no additional clinical utility beyond that provided by Mg-S, but requires unusual specimen handling to isolate packed red blood cells immediately after collection.

Since there is no demonstrable benefit to the red blood cell testing, we strongly recommend that nutritional assessment be accomplished using the serum magnesium (MGS/8448 Magnesium, Serum) and serum zinc (ZNS/8620 Zinc, Serum) tests.

Authored by Thomas Moyer, PhD

Transient Hypothyroidism is Most Commonly Seen in the Following Situations:

  1. Subacute thyroiditis (silent and symptomatic type) is acute or subacute inflammation of the thyroid gland NOT related to underlying autoimmune thyroid disease, but probably caused by host response to a pathogen that affects the gland. There is initial glandular destruction (hyperthyroid phase because of release of stored thyroid hormone), followed 2 to 6 weeks later by a hypothyroid phase (hormone stores depleted, parts of the thyroid destroyed), lasting 2 to 6 months, and then, usually within a year, complete recovery. However, 10% to 20% of patients will have lost so much thyroid tissue in the process that they do not recover and are left with permanent hypothyroidism.
  2. Postpartum thyroiditis is very similar to subacute thyroiditis, but autoimmune in etiology in predisposed women. It is thought to be triggered by the sudden immune system upregulation that takes place after delivery, as the immune system is quite suppressed during the second and third trimester. This thyroiditis does not have a pronounced hyperthyroid phase (more gradual development) but, again, the hypothyroid phase that ensues usually lasts no more than a year. Permanent hypothyroidism is seen in 20% to 40% of these women.
  3. Thyrotoxicosis hypothyroidism typically develops 4 to 10 weeks after radioiodine treatment. Depending on the dose given, and the uptake in the patient’s gland and the gland’s size, this may be permanent or transient. If transient, recovery can progress within a few months to a euthyroid state (with an increased risk of recurrence of thyrotoxicosis at some later stage).
  4. Drug-related hypothyroidism can occur with amiodarone and some of the interferones. The pathology is similar to typical autoimmune hypothyroidism. Drug-related hypothyroidism may or may not resolve when the drug is discontinued. In fact, often drug-related hypothyroidism does not resolve.


  1. Kuriyama C, Mori K, Nakagawa Y, et al: Erythrocyte zinc concentration as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism from permanent hypothyroidism. Endocrine Journal 2011; 58(1):59–63
  2. Prasad AS: Laboratory diagnosis of zinc deficiency. J Am Coll Nutr 1985; 4(6):591–598
  3. Sales CH, Pedrosa L, Lima JG, et al: Influence of magnesium status and magnesium intake  on the blood glucose control in patients with  type 2 diabetes. Clinical Nutrition 2011;30: 359–364
  4. Corica F, Allegra A, Ientile R, et al: Reduced intraplatelet magnesium concentrations in elderly patients with non-insulin dependent diabetes mellitus (NIDDM). Arch Gerontol Geriatr 1997;25:255–262