Featured article | June 2026
The Nutritional Relationships of Copper
Watts, D.L. (1989). Journal of Orthomolecular Medicine, 4(2), 99–108.
Copper serves as a cofactor for enzymes involved in iron metabolism, energy production, antioxidant defense, connective tissue formation, neurotransmitter synthesis, and histamine degradation. Watts argues that many manifestations of copper deficiency arise through impaired activity of these copper-dependent enzymes.
Discussed in the article:
Iron mobilization and utilization
- Ceruloplasmin, a copper-dependent ferroxidase, converts ferrous iron (Fe²⁺) into ferric iron (Fe³⁺), allowing transport by transferrin.
- Copper deficiency impairs ceruloplasmin activity and reduces the mobilization of iron from tissue stores.
- Iron can accumulate in tissues while functional iron deficiency develops elsewhere.
- Anemia may occur despite adequate or elevated tissue iron levels.
Cellular energy production
- Copper is a component of cytochrome c oxidase, the terminal enzyme of the mitochondrial electron transport chain.
- Cytochrome c oxidase is required for efficient oxygen utilization and ATP production.
- Copper deficiency compromises mitochondrial energy metabolism.
- Reduced energy production may contribute to fatigue and other deficiency symptoms.
Protection against oxidative stress
- Copper-zinc superoxide dismutase (Cu/Zn-SOD) neutralizes superoxide radicals generated during normal metabolism.
- Copper deficiency reduces Cu/Zn-SOD activity, weakening antioxidant defenses.
- Increased oxidative stress can promote tissue injury and inflammatory processes.
Connective tissue integrity
- Copper-dependent lysyl oxidase catalyzes cross-linking of collagen and elastin.
- Proper cross-linking strengthens blood vessels, bone, skin, and connective tissues.
- Copper deficiency impairs connective tissue formation and structural integrity.
Neurotransmitter synthesis
- Dopamine β-hydroxylase converts dopamine into norepinephrine.
- Copper is required for normal activity of this enzyme.
- Copper deficiency can reduce norepinephrine production, potentially affecting neurological function and stress adaptation.
Histamine regulation
- Diamine oxidase (histaminase) helps degrade histamine.
- Copper serves as a cofactor for this enzyme.
- Inadequate copper can reduce histamine degradation and alter histamine metabolism.
Pigment formation
- Copper-dependent tyrosinase participates in melanin synthesis.
- Deficiency can impair normal pigmentation.
Endocrine Influences on Copper
- Estrogen promotes copper retention and can increase tissue copper levels.
- Pregnancy and oral contraceptive use have been associated with elevated copper status.
- Hormonal influences should be considered when interpreting copper levels.
Copper functions within a larger nutrient network
- Copper metabolism is influenced by interactions with zinc, iron, manganese, selenium, molybdenum, and sulfur-containing compounds.
- Excessive intake of antagonistic nutrients can impair copper utilization.
- Functional deficiency can develop even when dietary copper intake appears adequate.
Why It Matters
Copper is often viewed as a minor trace mineral, yet it occupies critical positions in iron transport, mitochondrial energy production, antioxidant protection, connective tissue formation, neurotransmitter synthesis, and histamine metabolism. Deficiency can disrupt multiple physiological systems simultaneously through impaired enzyme function.
“Often the adverse effects of copper toxicity are given more consideration than copper deficiency. … Just as much consideration should be given to the possibility of copper deficiency as to copper toxicity.”
