Kresser Institute

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Functional Blood Chemistry Manual


Marker Name: Zinc


Laboratory reference range: 56–134 µg/dL

Functional reference range: 81–157 µg/dL


Zinc is a trace element that is essential for the proper function of approximately 250 proteins, at least 200 of which are enzymes.1 Zinc is a cofactor for carbonic anhydrase, alkaline phosphatase, and DNA polymerase, among many others.2 The mineral plays a vital role in cell growth and replication, immune system function, protein synthesis, DNA synthesis, bone and joint health, wound healing, and thyroid function.1-4 A steady supply of zinc is required for normal growth and development.5 Moreover, zinc is integral to the sense of taste and smell.4,6

A normal adult human contains between 1.5 and 3 grams of zinc at any given time.5,7 Roughly 60 percent of zinc in the body is contained within bone and muscle,7 though there is no specialized zinc storage system.4 Zinc undergoes very slow turnover; only 0.1 percent of total body zinc is replenished each day.5 The element is mainly absorbed in the upper small intestine and, to a lesser extent, in the lower small intestine and colon.8 Likewise, zinc is mainly excreted via the gastrointestinal tract, though 10 percent of circulating zinc may be secreted in the urine.7

Pancreatic enzymes release dietary zinc, which then forms complexes with organic acids, amino acids, and phosphates.9 Zinc homeostasis is mainly controlled by metallothionein, a metalloprotein found in gastrointestinal tract cells.7,10 Metallothionein binds not only to zinc, but also to other biologically important divalent ions, such as iron and copper. In fact, excess zinc intake can inhibit copper absorption by metallothionein.7,10

In the serum, 80 percent of zinc is carried by albumin, while most of the other 20 percent is shuttled by alpha-2-macroglobulin; the mineral is loosely bound to the former and tightly bound to the latter.1 Consequently, states of hypoalbuminemia can result in a higher-than-normal portion of zinc binding to macroglobulin, rendering it functionally unavailable (i.e., it is too tightly bound to dissociate for biological uses).1 Intracellular zinc may be bound to carrier molecules within cells. For example, metallothionein acts as a storage molecule for zinc in the liver.7

Elevated zinc (hyperzincemia) can occur through over-supplementation, by consuming contaminated foods, or through prolonged use of denture adhesives. Direct zinc toxicity from excess zinc consumption is rarely a clinical concern because of multiple homeostatic mechanisms. That is, excess ingested zinc is not absorbed by metallothionein in the gut, and excess zinc may be secreted by the gut into the intestinal lumen or by the kidney into the urine.10 Excessive zinc intake may be of concern when it causes hypocupremia, an abnormally low level of copper in the blood.10 Exposure to ZnO fumes, which may occur in galvanized metal welders, may lead to inhalation of enough zinc to cause acute toxicity.11

Low zinc levels (hypozincemia) can result from inadequate intake of zinc, zinc malabsorption, impaired zinc transport, or increased zinc loss. Inadequate intake of zinc may not be due to decreased consumption, but rather due to increased requirements for zinc (e.g., pregnancy, prolonged breast-feeding).12 Numerous drugs across many drug classes can cause zinc depletion.6

Plasma or serum levels are generally regarded as an acceptable indicator of zinc status in healthy individuals.5,10 During acute inflammatory states, however, plasma zinc is not a useful measurement, since plasma levels deplete.13 In these cases, zinc status can be accurately obtained by measuring zinc within red blood cells.13 Albumin and copper levels in the serum can provide critical information when evaluating serum zinc levels.10,12 Since erythrocytes carry appreciable amounts of zinc, hemolysis can cause serum zinc level to be falsely elevated.2 Gadolinium, iodine, and barium are known to interfere with serum metal testing.12


High in:11,14-17

  • Excess zinc supplementation
  • Inhalation of ZnO fumes
  • Prolonged use of denture adhesives
  • Familial hyperzincemia

Low in:8,9,12,18,19

  • Dietary inadequacy
    • Malnutrition
    • Vegetarian diets
    • Total parenteral nutrition (TPN) with inadequate zinc
    • Sickle cell anemia
    • Pregnancy
    • Prolonged breast-feeding
    • Severe burns
  • Decreased absorption
    • High-phytate diets
    • Inflammatory bowel disease
    • Bowel surgery
    • Chronic diarrhea
    • Necrotizing enterocolitis in pre-term infants
    • Acrodermatitis enteropathica
  • States of hypoalbuminemia (e.g., cirrhosis, nephrotic syndrome)
  • Drugs
    • Oral contraceptives
    • Antacids
    • Histamine H2 antagonists
    • Anti-inflammatories
    • Diuretics
    • Angiotensin-converting enzyme (ACE) inhibitors
    • Anticonvulsants
    • Antiretrovirals


High in:

  • Same as conventional indications

Low in:

  • Same as conventional indications


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