Zinc / Copper Ratio - Kresser Institute Membership Site

Marker Name: Zinc / Copper ratio

REFERENCE RANGE FOR ZINC/COPPER RATIO:

Functional reference range: 0.85–1.2

DESCRIPTION:

Zinc and copper are trace elements that are essential to the function of hundreds of proteins in humans. Zinc is a cofactor for RNA and DNA polymerase, carbonic anhydrase, alkaline phosphatase, and approximately 200 other enzymes.¹ Zinc is essential for cell signaling, growth and development, lipid metabolism, and nervous system and immune system function.² Copper is an integral component of numerous metalloenzymes involved in cellular respiration, collagen cross-linking, neurotransmitter synthesis, bone formation, and thrombosis, among others.^3,4

Zinc and copper can be found throughout the body, but 50 to 60 percent of total body stores of these minerals is held within bone and muscle.^3,5 In humans, total body copper content is between 50 and 120 mg, while zinc content is two orders of magnitude higher, between 1.5 and 3 grams.^3,6

Zinc and copper homeostasis are closely related; intestinal absorption of copper is inhibited by zinc within the gastrointestinal tract and vice versa.^1,7 Metallothionein, a metalloprotein that binds to various divalent ions, is responsible for copper and zinc absorption in the intestine.⁸ Metallothionein regulates zinc homeostasis, yet copper binds to the metalloprotein in gut enterocytes more avidly than zinc does.³ Moreover, metallothionein acts as a storage molecule for both zinc and copper in the liver.³

Both elements are transported in the blood by carrier proteins; albumin and macroglobulin carry zinc, while ceruloplasmin carries most copper.³ The same cytokines that increase the cellular uptake of zinc also enhance the production of ceruloplasmin in the liver.⁹

As a ratio, any etiology of increased serum zinc or decreased serum copper will necessarily increase the zinc/copper ratio. Further exacerbating this imbalance is the manner in which these divalent cations are absorbed in the gut; excess of one decreases the absorption of the other.^1,7 Conversely, the ratio may be abnormally low if zinc levels diminish, copper levels increase, or both changes occur.

Importantly, copper can be transiently elevated during acute inflammation, infection, or trauma, while serum levels of zinc may decrease.^4,10-12 Consequently, the zinc-to-copper ratio would decrease substantially. Under these clinical conditions, a more accurate assessment of copper and zinc can be gathered by assessing erythrocytes levels of each trace mineral.¹⁰

Zinc and copper may be measured within a trace minerals panel.¹³ Albumin and ceruloplasmin levels can provide important diagnostic information when evaluating zinc and copper abnormalities.^8,14

FUNCTIONAL RANGE INDICATIONS:

High in:^3,15-24

Excess zinc
- Megadose zinc supplementation
- Inhalation of ZnO fumes
- Prolonged use of denture adhesives
- Familial hyperzincemia
Decreased copper
- Menkes disease
- Excessive iron ingestion
- Chronic dialysis (hemodialysis, peritoneal dialysis)
- Prolonged total parenteral nutrition
- Aceruloplasminemia
- Gastrointestinal malabsorption
  - Post-gastrectomy
  - Post-gastric bypass surgery
  - Celiac disease
  - Inflammatory bowel disease
  - Chronic diarrhea
  - Cystic fibrosis
- Hypoproteinemia
  - Malnutrition
  - Nephrotic syndrome
- Drugs
  - Corticosteroids
  - Clioquinol
  - Tetrathiomolybdate

Low in:^{3,11,14,20,25-31}

Excess copper
- Wilson disease
- Normal pregnancy
- Excessive copper intake
- Hyperthyroidism
- Hemochromatosis
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Drugs
  - Oral contraceptives
  - Estrogens
  - Carbamazepine
  - Phenobarbital
- Decreased zinc
  - States of hypoalbuminemia (e.g., cirrhosis, nephrotic syndrome)
  - Dietary inadequacy
    - Malnutrition
    - Strict vegetarian diets
    - Total parenteral nutrition (TPN) with inadequate zinc
    - Sickle cell anemia
    - Pregnancy (normal or abnormal)
    - Prolonged breastfeeding
    - Severe burns
  - Decreased absorption
    - High-phytate diets
    - Inflammatory bowel disease
    - Bowel surgery
    - Chronic diarrhea
    - Necrotizing enterocolitis in preterm infants
    - Acrodermatitis enteropathica
  - Drugs
    - Antacids
    - Histamine H₂ antagonists
    - Oral contraceptives
    - Anti-inflammatories
    - Diuretics
    - Angiotensin-converting enzyme (ACE) inhibitors
    - Anticonvulsants
    - Antiretrovirals
  - Increased copper and decreased zinc
    - Infarction
    - Coronary artery disease
    - Infection
    - Inflammation
    - Neoplastic disease (e.g., leukemia)
    - Trauma
    - Renal failure

References: