Mineral Biomarkers: RBC Zinc

Optimal Takeaways

Red blood cell (RBC) zinc levels offer a more stable indicator of long-term zinc status, unaffected by acute changes like dietary intake, stress, or inflammation. Furthermore, RBC zinc can help differentiate between types of thyrotoxicosis and indicate whether hypothyroidism is transient or permanent. 

Lower RBC zinc levels are observed in conditions such as obesity and hyperthyroidism, with implications for metabolic dysfunctions like insulin resistance and inflammation. Prolonged insufficient zinc intake can impact RBC zinc levels, impairing cardiorespiratory function and physical performance. High RBC zinc levels could signal zinc toxicity. 

Standard Range: 9.00 – 14.70 mg/L (137.62 – 224.78 umol/L)

The ODX Range: 10.40 – 14.70 mg/L (159.03 – 224.78 umol/L)

Low red blood cell zinc levels may be associated with hyperthyroidism (Sayama 1998, Yoshida 1990), obesity, metabolic syndrome (Olechnowicz 2018), medications such as captopril or valsartan (Braun 2013), decreased enzyme activity, cardiorespiratory function, and physical activity (Lukaski 2005).

High red blood cell zinc levels may be associated with excess zinc exposure and toxicity.

Overview

Red blood cell zinc levels may better reflect long-term zinc status as they are not as acutely affected by eating, stress, inflammation, infection, hormone therapy, steroids, or mild zinc deficiency as are serum levels. In mild deficiency, the body can redistribute zinc from tissues into circulation to maintain serum levels despite zinc insufficiency (Noland 2020).

Red blood cell zinc levels are lower in obesity and maintain an inverse association with waist circumference and BMI. Compromised zinc status in obesity contributes to characteristic metabolic dysfunctions, including dyslipidemia, insulin resistance, and inflammation. Research indicates that zinc replenishment can improve blood glucose, blood pressure, and LDL-cholesterol levels (Olechnowicz 2018).

Red blood cell zinc is lower in hyperthyroidism, inversely related to plasma T4, and can be used to differentiate Graves from transient thyrotoxicosis. In one study of 90 subjects, mean RBC zinc was 12.6 mg/L (192.7 umol/L) in euthyroid controls, 12.0 mg/L (183.5 umol/L) in silent thyroiditis, 11.8 mg/L (180.5 umol/L) in gestational thyrotoxicosis, and only 7.3 mg/L (111.7 umol/L) in Graves’ disease (Sayama 1998). An earlier study observed a lower RBC zinc of 6.4 mg/L (97.9 umol/L) in hyperthyroid patients. Researchers note that RBC zinc had a significant inverse correlation with plasma thyroid hormones (Yoshida 1990).

Measuring RBC zinc can also help distinguish thyroiditis-associated transient hypothyroidism from permanent hypothyroidism. One study found that RBC zinc was significantly lower in transient hypothyroidism versus permanent hypothyroidism. Researchers found that an RBC zinc below a cut-off of 12 mg/L (183.5 umol/L) may indicate that hypothyroidism is transient and potentially reversible. In contrast, those with permanent hypothyroidism maintained an RBC zinc of 12 mg/dL or above (Kuriyama 2011).

Although RBC zinc is not as sensitive to short-term changes in dietary intake as serum zinc, prolonged insufficient intake can reduce both levels. One double-blind, randomized cross-over of 14 young adult males found that low dietary zinc intake (~3.8 mg/day) resulted in significant reductions in serum zinc, RBC zinc, and carbonic anhydrase, the enzyme responsible for the reversible conversion of carbon dioxide to carbonic acid. Low zinc status impaired cardiorespiratory function and physical performance in this study (Lukaski 2005).

References

Braun, L A, and F Rosenfeldt. “Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy.” International journal of clinical practice vol. 67,8 (2013): 717-25. doi:10.1111/ijcp.12040

Kuriyama, Chizuko et al. “Erythrocyte zinc concentration as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism from permanent hypothyroidism.” Endocrine journal vol. 58,1 (2011): 59-63. doi:10.1507/endocrj.k10e-152

Lukaski, Henry C. “Low dietary zinc decreases erythrocyte carbonic anhydrase activities and impairs cardiorespiratory function in men during exercise.” The American journal of clinical nutrition vol. 81,5 (2005): 1045-51. doi:10.1093/ajcn/81.5.1045

Olechnowicz, J et al. “Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism.” The journal of physiological sciences : JPS vol. 68,1 (2018): 19-31. doi:10.1007/s12576-017-0571-7

Sayama, N et al. “Measurement of red blood cell zinc concentration with Zn-test kit: discrimination between hyperthyroid Graves' disease and transient thyrotoxicosis.” Endocrine journal vol. 45,6 (1998): 767-72. doi:10.1507/endocrj.45.767

Yoshida, K et al. “Erythrocyte zinc in hyperthyroidism: reflection of integrated thyroid hormone levels over the previous few months.” Metabolism: clinical and experimental vol. 39,2 (1990): 182-6. doi:10.1016/0026-0495(90)90073-l