Mineral Biomarkers: Serum Zinc

Optimal Takeaways

Zinc is an essential micronutrient that participates in numerous metabolic functions, including carbohydrate, protein, fat, DNA, and RNA metabolism, glucose regulation, acid-base balance, digestion, antioxidant activity, immunity, wound healing, thyroid hormone production, and heme synthesis. A zinc deficiency compromises each function and contributes to chronic disease. An excess of zinc can be toxic and can cause severe metabolic consequences.

Standard Range: 50.00 – 130.00 ug/dL (7.64 – 19.88 umol/L)

The ODX Range: 99 - 130 ug/dL (15.15 - 19.89 umol/L)

Low serum zinc may be associated with diarrhea, skin rash, hypogeusia, anorexia, alopecia, vision problems, disruptions in acid-base balance, reduced alkaline phosphatase activity, decreased breakdown of alcohols, compromised protein digestion, decreased heme production, reduced folate absorption, diminished insulin signaling, and impaired protein synthesis, wound healing, and immunity. Levels can also decline with stress, infection, and steroid therapy (Gropper 2021).

Low levels are also associated with Crohn’s disease, increased intestinal permeability, “leaky gut”, cancer including gastrointestinal, gallbladder, lung, prostate, ovarian, and head and neck cancer (Skrovanek 2014), hypothyroidism and subclinical hypothyroidism (Betsy 2013), stress, infection, inflammation (Noland 2020), low prealbumin (Pagana 2021), proton pump inhibitor use (Farrell 2011, Skrovanek 2014), and low alkaline phosphatase (Ray 2017).

Zinc insufficiency may be associated with atherosclerosis, obesity, diabetes, immune deficiency (Skalny 2020), metabolic syndrome, diabetes, hypertension (Olechnowicz 2018), inflammation, stunted growth, impaired taste and smell, sexual dysfunction, emotional lability (Maxfield 2021), depression, alopecia (Yanagisawa 2004), and iron deficiency anemia (Kelkitli 2016).

High serum zinc may be associated with zinc toxicity, copper deficiency, headache, GI upset, nausea, vomiting, bloody diarrhea, metallic taste, and immune suppression (Gropper 2021). Increased serum zinc is associated with flare-ups of ulcerative colitis and is accompanied by elevated complement component C3C and antinuclear antibodies (Skrovanek 2014).

Overview

Zinc is an essential trace mineral found throughout the body and participates in hundreds of metabolic functions, including the metabolism of carbohydrates, protein, lipids, and nucleic acids. Several enzymes require zinc, including hydrolases, isomerases, ligases, lyases, oxidoreductases, and transferases. Specific enzymes that depend on zinc include carbonic anhydrase (acid-base balance, CO2 metabolism), alkaline phosphatase (phosphate ­release), alcohol dehydrogenase (vitamin A metabolism, alcohol metabolism), carboxypeptidase and aminopeptidase (protein digestion), superoxide dismutase (antioxidant activity), phospholipase C (phospholipid metabolism), polyglutamate hydrolase (releases folate from food), and delta-aminolevulinic acid dehydratase (heme synthesis) to name a few (Gropper 2021).

Zinc plays a vital role in gastrointestinal health, especially in maintaining the integrity and function of the gut epithelial barrier. Zinc insufficiency can increase intestinal hyperpermeability, contributing to “leaky gut syndrome.” Diarrhea is a common manifestation of zinc deficiency, and levels should be assessed and addressed promptly. Zinc insufficiency is common in GI disorders, including celiac and Crohn’s, and should be replenished appropriately. Zinc supplementation has been found to improve tight junctions and potentially reduce the migration of white blood cells and antigens across the mucosal barrier. Excess intake of phytates, found in whole grains, nuts, and seeds, can bind zinc and reduce its absorption, contributing to insufficiency (Skrovanek 2014),

Chronic use of proton pump inhibitors (PPIs) can reduce serum zinc and contribute to deficiency. In one small study, PPI users had significantly lower mean serum zinc of 75 ug/dL (11.5 umol/L) versus controls with a mean of 91 ug/dL (13.9 umol/L) (Farrell 2011).

Zinc also supports cell membrane function, insulin metabolism, taste acuity, basal metabolic rate regulation, and immune competence. A serum below 70 ug/dL (10 umol/L) suggests zinc deficiency. It is associated with diarrhea, skin rash, hypogeusia, anorexia, alopecia, vision problems, lethargy, depression, impaired protein synthesis, delayed wound healing, and compromised immunity. Excess zinc can disrupt the same metabolic processes, and supplementation at levels as low as 40 mg/day can induce a copper deficiency (Gropper 2021).

Additional signs of zinc insufficiency may include mental disturbance, emotional liability, irritability, impaired taste and smell, recurrent infections, dermatitis, hair and nail changes, night blindness, photophobia, hypogonadism, low bone mineral density, and stunted growth (Maxfield 2021).

Zinc is also required for thyroid hormone production, while thyroid hormone is needed for zinc absorption. One case study of an individual with hypothyroidism, weakness, anorexia, depression, alopecia, scaly skin lesions, and a serum zinc of 62 ug/dL (9.49 umol/L). These clinical symptoms didn’t improve with thyroid replacement but did improve dramatically with zinc supplementation and a multivitamin supplement (Betsy 2013). Decreased serum zinc is also seen in hyperthyroidism. A cross-sectional observational study of41 hyperthyroid subjects found that serum zinc was significantly lower at 48.93 mg/dL (7.49 umol/L) versus 90.59 mg/dL (13.86 umol/L) in controls (Sinha 2015).

Glucose tolerance is affected by zinc status as it is required to convert proinsulin to insulin and facilitates glucose transport into the cell. Research notes that zinc improves insulin sensitivity and reduces chronic hyperglycemia in type 2 diabetes (Cruz 2015). One cross-sectional study found a mean serum zinc level of 77.8 ug/dL (11.9 umol/L) in those with type 2 diabetes versus 95.4 ug/dL (14.6 umol/L) in controls (Olaniyan 2012).

Zinc’s role in immunity is crucial as it regulates antibacterial and antiviral immunity and the inflammatory response. Research suggests that serum zinc above 70 ug/dl (10.8 umol/L) reduces the risk of pneumonia, especially severe pneumonia, as well as prolonged illness and all-cause mortality (Skalny 2020).

The antioxidant functions of zinc are essential to health in general and apply to athletic performance. In one study of elite athletes, plasma zinc ranged from 96.7-124.8 mg/dL (14.8-19.1 umol/L). Researchers note that aerobic activity was associated with increased zinc uptake into the RBC with increased concentrations of erythrocyte metallothionein and superoxide dismutase, suggesting an adaptive increase in antioxidant capacity (Koury 2004).

Zinc can be displaced by toxins such as cadmium found in tobacco smoke. In a study of 254 apparently healthy males, 127 of whom were smokers, marginal zinc deficiency of 50-70 ug/dL (7.65-10.7 umol/L) was more common in those who smoked, as were elevated biomarkers of oxidative stress, including ceruloplasmin, total glutathione, malondialdehyde, and peroxynitrite (Mohammad 2010).

Iron metabolism depends on zinc; low zinc status is associated with iron deficiency anemia (IDA). One study of 43 IDA patients and 43 controls found that those with anemia and serum zinc below 99 ug/dL (15.15 umol/L) had significantly more neuromuscular signs of restless leg syndrome; cardiopulmonary symptoms, including shortness of breath, palpitations, and dizziness; cognitive symptoms including forgetfulness, slow thinking, and difficulty with tasks; and more epithelial manifestations including hair and nail changes, stomatitis, cheilosis, glossitis, and easy bruising (Kelkitli 2016).

References

Betsy, Ambooken et al. “Zinc deficiency associated with hypothyroidism: an overlooked cause of severe alopecia.” International journal of trichology vol. 5,1 (2013): 40-2. doi:10.4103/0974-7753.114714

Cruz, Kyria Jayanne Clímaco et al. “Antioxidant role of zinc in diabetes mellitus.” World journal of diabetes vol. 6,2 (2015): 333-7. doi:10.4239/wjd.v6.i2.333

Farrell, Christopher P et al. “Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores.” Gastroenterology research vol. 4,6 (2011): 243-251. doi:10.4021/gr379w

Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P. Advanced Nutrition and Human Metabolism. 8th edition. Wadsworth Publishing Co Inc. 2021.

Kelkitli, Engin et al. “Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia.” Annals of hematology vol. 95,5 (2016): 751-6. doi:10.1007/s00277-016-2628-8

Koury, Josely C et al. “Zinc and copper biochemical indices of antioxidant status in elite athletes of different modalities.” International journal of sport nutrition and exercise metabolism vol. 14,3 (2004): 358-72. doi:10.1123/ijsnem.14.3.358

Maxfield, Luke, et al. “Zinc Deficiency.” StatPearls, StatPearls Publishing, 28 November 2021.

MOHAMMAD, BAHEEJ Y., M. R. Haji, and D. J. Al-Tamimi. "Zinc status among smokers and non-smokers: Relation to oxidative stress." (2010): 67-73.

Noland, Diana, Jeanne A. Drisko, and Leigh Wagner, eds. Integrative and functional medical nutrition therapy: principles and practices. Springer Nature, 2020.

Olaniyan, O. O., et al. "Serum copper and zinc levels in Nigerian type 2 diabetic patients." African Journal of Diabetes Medicine Vol 20.2 (2012).

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

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Ray, Chinmaya Sundar, et al. "Low alkaline phosphatase (ALP) in adult population an indicator of zinc (Zn) and magnesium (Mg) deficiency." Current Research in Nutrition and Food Science Journal 5.3 (2017): 347-352.

Sinha, S., Kar, K., Dasgupta, A., Basu, S., & Sen, S. (2015). Correlation of Serum zinc with TSH in hyperthyroidism. Asian Journal of Medical Sciences, 7(1), 66-69.

Skalny, Anatoly V et al. “Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review).” International journal of molecular medicine vol. 46,1 (2020): 17-26. doi:10.3892/ijmm.2020.4575

Skrovanek, Sonja et al. “Zinc and gastrointestinal disease.” World journal of gastrointestinal pathophysiology vol. 5,4 (2014): 496-513. doi:10.4291/wjgp.v5.i4.496

Yanagisawa, Hiroyuki. "Zinc deficiency and clinical practice." Japan Medical Association Journal 47.8 (2004): 359-364.