Copper

Copper is a natural essential mineral belonging to the supplement class.

Copper is also known as Cu or cuprum.

Copper is vital for healthy immunological function, blood sugar regulation, cellular energy, reproduction, digestion, bone formation, blood clotting, hemostasis, and protection against reactive oxygen species.

Copper deficiency leads to anaemia (microcytic, normocytic, or macrocytic), neutropenia and CNS damage like myelopathy and peripheral neuropathy.

The foods highest in dietary copper are seeds, nuts, organ meats, shellfish like oysters, wheat-bran cereals, potatoes, mushrooms, durian, avocados, chickpeas, tofu, whole-grain goods, and chocolate.

Copper is primarily absorbed in the small intestine and transported by blood to tissues, contributing to bone growth and brain function. Excess copper is excreted from the body via bile and urine.

The common side effects of copper include nausea, vomiting, bloody diarrhoea and fever.

Copper is available in tablets, capsules and injectable solutions.

Biochemical Action of Copper

Copper belonging to the supplement class helps in a number of physiological processes. Copper acts via copper enzyme-mediated biochemical pathways.

Copper absorption takes place primarily in the small intestine. Enterocytes take up copper by means of copper transporter 1 (CTR1), a copper importer found at the apical membrane (the free surface that is exposed to the luminal fluid) of intestinal cells and most tissues. The exporter ATP7A transports copper from enterocytes to the circulation. Most of the copper in portal circulation is bound to the transporter protein ceruloplasmin. When copper-bound ceruloplasmin attaches to ceruloplasmin receptors, copper is taken up by the liver. Protein metallochaperones in hepatocytes serve to allocate and transport copper to specific routes throughout the body. The copper exporter ATP7B transports copper from the hepatocyte. Excess copper is eliminated in the faeces after being released into the bile.

Copper is available in tablets, capsules and injectable solutions.

• Tablets/capsules: To be swallowed whole with water/liquid, as applicable.
• Injectable solutions: To be administered parenterally, as applicable.

Copper can be used as a supplement when the amount of copper taken from the diet is insufficient.

Copper supplements taken by mouth or IV may be used to prevent and treat copper deficiency, a condition in which the body needs copper.

Adequate oral intake of copper supplements in combination with zinc, manganese, and calcium by older women might help reduce osteoporosis.

The copper supplement helps in fat and carbohydrate metabolism, calcium absorption, and blood sugar regulation.

Copper supplements may support healthy immunological function and neuronal cells.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Copper may be useful as a supplement for the following health benefits:

• Cardiovascular disease: Studies on the effects of copper intake on heart disease have resulted in contradictory findings. More research is needed to determine whether consuming more copper through food or supplements increases or decreases the risk of cardiovascular disease.
• Immunity: White blood cell production and immune cell function are enhanced by copper, which supports the body's ability to fight infections, thus strengthening the immune system. It also maintains a robust immune response and helps defend the body against diseases.
• Enzyme cofactor: A group of cellular transporters known as cuproenzymes require copper as a vital component. By serving as an essential cofactor, copper helps produce enzymes and promotes critical physiological activities like energy synthesis, antioxidant defence, connective tissue development, and iron metabolism.
• Iron absorption: Copper supports the formation of red blood cells and prevents anaemia by facilitating the body's absorption and absorption of iron from the diet. It promotes efficient oxygen delivery for general health as well as the formation of red blood cells and anaemia prevention.
• Osteoporosis: The growth and maintenance of bones and connective tissues are influenced by copper. By helping skeletal tissues grow and remain healthy, copper promotes the production of bones. This process supports bone health and structural integrity, maintaining solid and robust bones throughout every stage of life.
• Antioxidant: Copper could serve as an antioxidant. It might help lower the generation of free radicals, which can damage DNA and cells, resulting in cancer and other disorders. Enzymes containing copper are active in antioxidant processes that defend cells from oxidative damage and support general cellular health.
• Collagen production: Collagen and elastin require copper for functioning structural Collagen production: processes. It has been demonstrated by several investigations that copper availability can regulate the formation of mature collagen and elastin. Without enough copper, the body can't repair damaged collagen or connective tissue and may cause several complications, including joint dysfunction.
• Pigmentation: By activating the tyrosinase enzyme, copper regulates pigmentation. Melanin is the pigment responsible for the colour of your skin, hair, and eyes, and is produced with the help of this enzyme. Copper's contribution to tyrosinase activity influences diverse human pigmentation variations.

Copper supplementation may be administered orally or parenterally.

• Orally: Copper supplements are available as tablets and capsules that can be taken orally. It is best taken with a meal or food.
• Parenterally: Copper supplements are generally taken by mouth but may have to be administered intravenously to all patients who require parenteral nutrition (PN).

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablet: 5mg
• Capsule: 5mg
• Injectable solutions: 0.4mg/mL (10mL)

Copper is available in tablets, capsules and injectable solutions.

Copper should be used as a supplement that helps in a number of physiological processes along with appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Avoid smoking cigarettes.
• Limit foods and drinks that are higher in added sugars, saturated fat, and sodium.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

The RDA of copper is 900 μg/day.

Upper Tolerable Intake (UTL):

The UTL set for copper is 10,000 μg/day (10 mg/day)

Copper supplementation may be contraindicated in the following conditions:

• Hypersensitivity; sensitive to copper
• Wilson's disease
• Chronic kidney disease
• Hepatic impairment
• Idiopathic copper toxicosis
• Childhood cirrhosis
• Pheochromocytoma
• Copperoma
• Insulinoma

For individuals on hemodialysis, copper from supplements might need to be absorbed better in people.

Copper supplements should be used cautiously in liver/biliary tract dysfunction.

Since the copper supplement is acidic in nature, it should be cautiously administered intravenously or intramuscularly directly without dilution may cause tissue damage.

Aluminium is present in the injection; use caution in patients with renal impairment and premature newborns.

Caution is advised when consuming alcohol with copper.

Excreted in breastmilk is unclear; Use cautiously during breastfeeding.

Unsafe to use during pregnancy.

Limit the consumption of foods and beverages higher in added sugars, saturated fat, and sodium alcoholic beverages, as these substances could hinder copper absorption.

The adverse reactions related to copper can be categorized as-

• Common: Nausea, vomiting, abdominal pain, metallic taste and diarrhoea
• Less Common: Headaches, fatigue and allergic reactions.
• Rare: Kidney damage, hemolytic anaemia and neurological effects

The common side of copper includes the following:

• Nausea

• Vomiting

• Bloody diarrhoea

• Stomach pain

• Dizziness

• Fever

• Low blood pressure

• Anaemia

• Heart problems.

• Weakness

• Metallic taste in the mouth

The use of copper should be prudent in the following group of special populations.

• Pregnancy:

Pregnancy Category: C. Safe during pregnancy, but when taken in high doses, use with caution if the benefits outweigh the risks.

The RDA for copper in pregnant women is 1000 mcg/day.

• Paediatrics:

The maintenance of newborn growth, host defence systems, bone density, red and white cell maturation, iron transport, cholesterol and glucose metabolism, cardiac contractility, and brain development in children require copper dietary supplements.

Copper supplements are the best way to help children get enough copper daily.

The RDA for Copper in paediatrics ranges from 200-890 mcg/day.

Dosage Adjustment for Paediatric Patients

Dietary Supplement

Parenteral nutrition: 20 mcg copper/kg/day IV.

• Geriatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of Copper for use in special populations.

• Lactating mothers:

When consumed more than RDA, copper may excrete the breast milk and harm a breastfeeding infant, so it is advised to use it cautiously.

The RDA for copper in lactating mothers is 1300 mcg/day.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment for Adult Patients

Dietary Supplement

2-5 mg PO qDay or more; not to exceed 8 mg/day

Alternatively (parenteral nutrition): 0.3-0.5 mg/day IV or 0.5-1.5 mg/day IV (per manufacturer)

High Output Fistula

May use twice the recommended daily allowance.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of copper. Overdosing on copper supplements may cause symptoms such as nausea and vomiting, liver damage and neurological problems.

There is no specific antidote or treatment for excessive intake of supplemental copper. When an overdose is suspected, Copper supplements should be terminated immediately and in severe cases, chelating agents like D-penicillamine will help remove excess copper from the body. Supportive and physical therapy might be added if necessary.

Biochemistry Profile of Copper

An essential trace mineral known as copper is an integral component of numerous proteins, including a significant number of enzymes. Cu+ and Cu2+ are the two forms of the transition metal copper. Copper's cuprous reduced state is known as Cu+. The oxidised cupric form of copper is known as Cu2+. In contrast to being consumed and moving through the bloodstream in its oxidised state, copper is absorbed into cells in its reduced form. The central nervous system's structure and function, skeletal and cardiovascular development, and erythropoietic processes like iron metabolism are all controlled by copper. Although widespread copper shortage in the human population is not proven, it rarely happens due to genetic disorders and other triggering factors.

Kinetic profile:

• Absorption: Copper is absorbed mainly in the stomach and small intestine. It is absorbed in the form of free copper ions and copper complexes created with amino acids. To maintain the body's copper equilibrium, the absorption process is regulated.
• Distribution: Copper is transported through the bloodstream after absorption, mostly bound to a protein called ceruloplasmin. It is found in a variety of tissues and organs, including the liver, brain, kidneys, and muscles, where it plays an important part in enzyme functioning.

• Metabolism: Copper is used by enzymes involved in various metabolic activities in cells, including energy synthesis, iron metabolism, and antioxidant defence. Copper metabolism is essential due to its role in electron transport within the mitochondria.
• Elimination: • Excess copper and copper metabolites are mostly eliminated via the liver as bile. Copper gets transported to the intestines by bile and subsequently excreted in the faeces. A minor amount of copper is also expelled in the urine.

1. https://www.ncbi.nlm.nih.gov/books/NBK222312
2. https://www.ncbi.nlm.nih.gov/books/NBK554545/
3. https://ods.od.nih.gov/factsheets/Copper-Consumer/

4. National Institute of Nutrition. 2011. Dietary guidelines for Indians; 2nd Edition. Hyderabad. India

5. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf