Copper (Gluconate/Bisglycinate)
1. Introduction – What is the product, chemical/botanical basics, mechanism of action
Copper is an essential trace mineral vital for the survival of all living organisms. It is naturally present in many foods and is available as a dietary supplement, often in the form of copper gluconate or copper bisglycinate. Copper is a necessary cofactor for several enzymes, known as cuproenzymes, which are involved in a wide range of physiological processes in the human body [1].
Copper Gluconate is the copper salt of D-gluconic acid. It is one of the most common forms of copper found in dietary supplements and is generally considered to have good, intermediate bioavailability [2].
Copper Bisglycinate (also known as copper glycinate chelate) is a form where the copper ion is chelated (bonded) to two molecules of the amino acid glycine. This chelated structure protects the mineral from interacting with other compounds in the gut, which is thought to enhance its absorption directly into the bloodstream, resulting in superior bioavailability compared to other forms like gluconate or sulfate [2, 3].
Mechanism of Action
Copper’s primary mechanism of action is its role as a cofactor for cuproenzymes. These enzymes catalyze critical reactions:
- Ceruloplasmin (CP): This is the most abundant cuproenzyme in the blood, carrying over 95% of total plasma copper. It acts as an oxidase, playing a key role in iron metabolism by oxidizing ferrous iron (Fe²⁺) to ferric iron (Fe³⁺), allowing it to bind to transferrin for transport [1].
- Superoxide Dismutase (SOD): Copper-zinc SOD (Cu/Zn-SOD) is a major antioxidant enzyme that catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide, providing crucial defense against oxidative damage [1].
- Cytochrome c Oxidase (CCO): This enzyme is the terminal component of the electron transport chain in mitochondria, essential for cellular energy production (ATP synthesis) [3].
- Lysyl Oxidase (LOX): This enzyme is copper-dependent and required for the cross-linking of collagen and elastin, which is fundamental for the integrity of connective tissue, bone, and blood vessels [1].
2. Chemical Composition/Key Bioactive Roles
| Compound | Chemical Basis | Key Bioactive Role |
|---|---|---|
| Copper (Cu) | Essential trace mineral | Cofactor for cuproenzymes, necessary for numerous metabolic pathways. |
| Copper Gluconate | Copper salt of D-gluconic acid | Supplement form with good bioavailability; provides elemental copper. |
| Copper Bisglycinate | Copper chelated with two glycine molecules | Supplement form with high bioavailability; provides elemental copper. |
| Ceruloplasmin (CP) | Copper-dependent enzyme | Iron metabolism, antioxidant activity, copper transport. |
| Superoxide Dismutase (SOD) | Copper-dependent enzyme | Primary defense against cellular oxidative stress. |
| Lysyl Oxidase (LOX) | Copper-dependent enzyme | Cross-linking of collagen and elastin for connective tissue strength. |
3. Health Benefits – Detailed health benefits with scientific evidence (cite studies)
Copper is essential for maintaining health across multiple systems, with benefits primarily derived from its enzymatic functions.
A. Iron Metabolism and Red Blood Cell Formation
Copper is crucial for the proper utilization of iron. The cuproenzyme ceruloplasmin oxidizes iron, enabling its transport and subsequent use in the formation of hemoglobin and red blood cells. Copper deficiency can lead to secondary iron-deficiency anemia because iron cannot be properly mobilized from storage sites [1]. Copper supplementation, therefore, supports healthy iron status and prevents this type of anemia [1].
B. Connective Tissue and Bone Health
Copper is required for the activity of lysyl oxidase, an enzyme that cross-links collagen and elastin, the major structural proteins in the body. This function is vital for the formation and maintenance of strong bone, cartilage, skin, and blood vessels [1]. Studies in animals and humans have shown that copper deficiency can lead to connective tissue disorders and bone defects, including osteoporosis [1, 4]. Supplementation with copper (2.5–3 mg/day) has shown good results in slowing down bone mineral loss in some studies [5].
C. Antioxidant Defense
As a component of the antioxidant enzyme Cu/Zn-SOD, copper plays a significant role in protecting cells from damage caused by free radicals. This enzyme converts the highly reactive superoxide radical into less harmful molecules, thereby reducing oxidative stress, which is implicated in aging and various chronic diseases [1, 3].
D. Immune System Function
Copper is necessary for the normal development and maintenance of the immune system. Copper deficiency is associated with an increased risk of infection and impaired immune response, including neutropenia (low white blood cell count) [1, 4].
E. Cardiovascular Health
Copper deficiency is linked to changes in blood lipid levels and cardiac abnormalities in animal models [1]. While observational studies in humans have yielded mixed results regarding copper levels and cardiovascular disease (CVD) risk, copper’s role in maintaining the structural integrity of the heart and blood vessels through its function in connective tissue synthesis is well-established [1, 6].
4. Dosage and Usage – Recommended dosages, food sources if applicable
Recommended Dietary Allowances (RDA)
The Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine established the following Recommended Dietary Allowances (RDAs) for copper [1]:
| Age Group | RDA (mcg/day) | RDA (mg/day) |
|---|---|---|
| Adults (19+ years) | 900 mcg | 0.9 mg |
| Pregnancy | 1,000 mcg | 1.0 mg |
| Lactation | 1,300 mcg | 1.3 mg |
Supplementation Dosages
Copper supplements typically contain elemental copper ranging from a few micrograms up to 15 mg [1]. Common dosages found in multivitamin/mineral supplements are often around the RDA (0.9 mg) or slightly higher (1-2 mg).
- For correcting deficiency: Dosages used in clinical studies to correct deficiency or support specific health outcomes, such as bone mineral loss, have often been in the range of 2–3 mg per day of elemental copper [5].
- General supplementation: For healthy adults, a daily supplement dose of 1-2 mg (1,000-2,000 mcg) of elemental copper is common and generally considered safe, provided the total daily intake (from food and supplements) remains below the Tolerable Upper Intake Level (UL).
Food Sources
The richest dietary sources of copper include shellfish, seeds and nuts, organ meats (especially liver), whole-grain products, and chocolate [1].
| Food Source | Copper Content per Serving (approximate) |
|---|---|
| Beef liver, pan fried (3 oz) | 12,400 mcg (12.4 mg) |
| Oysters, eastern, cooked (3 oz) | 4,850 mcg (4.85 mg) |
| Cashew nuts, dry roasted (1 oz) | 629 mcg (0.63 mg) |
| Dark chocolate (70%–85% cacao, 1 oz) | 501 mcg (0.50 mg) |
5. Safety and Precautions – Side effects, contraindications, drug interactions, warnings
Tolerable Upper Intake Level (UL)
The FNB has established a Tolerable Upper Intake Level (UL) for copper from food and supplements for healthy individuals, based on the level associated with liver damage [1]:
- Adults (19+ years): 10,000 mcg (10 mg) per day
Side Effects
Acute copper toxicity from high-dose supplementation can cause gastrointestinal symptoms, including [1]:
- Abdominal pain and cramps
- Nausea, vomiting, and diarrhea
Chronic exposure to excessive copper can result in liver damage [1].
Contraindications and Warnings
- Wilson’s Disease (Serious Warning): Individuals with Wilson’s disease, a rare genetic disorder that causes defective copper clearance, are at an extremely high risk of copper toxicity and should strictly avoid copper supplements. These individuals require lifelong medical management to reduce copper levels [1].
- High-Dose Zinc Supplementation: High dietary intakes of zinc (e.g., 60 mg/day or more) can interfere with copper absorption and may lead to copper deficiency. Individuals taking high doses of zinc supplements should consider supplementing with copper to maintain balance [1].
- Cognitive Decline: Some research suggests that high total copper intake (above 2.75 mg/day) in individuals consuming a diet high in saturated and trans fats may be associated with a faster rate of cognitive decline. Experts have suggested that individuals at increased risk of Alzheimer’s disease may consider using multivitamin/mineral supplements that do not contain copper [1].
Drug Interactions
Copper is not known to have any clinically relevant interactions with common prescription medications [1]. However, individuals on long-term medications should consult a healthcare provider before starting copper supplementation.
6. References
[1] National Institutes of Health, Office of Dietary Supplements. Copper – Health Professional Fact Sheet. https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/[2] NutriAvenue. Copper Gluconate VS Copper Glycinate: Which Is Better? https://www.nutriavenue.com/copper-gluconate-vs-copper-glycinate/[3] OptiVenture. Why Hikers Need Copper Bisglycinate Chelate for Energy & Recovery. https://optiventure.co/blogs/ingredient-spotlights/copper-copper-bisglycinate-chelate[4] Prohaska JR. Impact of copper deficiency in humans. Ann N Y Acad Sci 2014;1314:1-5. https://pubmed.ncbi.nlm.nih.gov/24758778/[5] Rondanelli M, et al. Copper as Dietary Supplement for Bone Metabolism: A Review of the Literature. Nutrients 2021 Jul 29;13(8):2616. https://pmc.ncbi.nlm.nih.gov/articles/PMC8308383/[6] Ford ES. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol 2000;151:1182-8. https://pubmed.ncbi.nlm.nih.gov/10853634/Category: Mineral
