Zinc

Biochemical action of zinc

Zinc belonging to the supplement class acts as a signalling agent and helps regulate muscle contraction, neurotransmitter release, hormone secretion, and gene expression. Zinc acts via Zinc homeostasis.

In the small intestine, zinc is absorbed via carrier-mediated transport, with the ZIP4 protein facilitating zinc uptake into intestinal cells and the ZNT1 protein releasing it into the bloodstream. After entering the bloodstream, zinc binds to albumin, a plasma protein. Zinc transporters are abundant in many tissues and help to regulate zinc homeostasis. Zinc is mostly excreted in the faeces. This highly regulated system provides zinc availability for vital physiological functions like as enzyme activity, DNA synthesis, immunological response, and growth while limiting excessive buildup, which could lead to toxicity and harmful effects.

Half-life: 11 days after cessation of therapy (inhibition of copper uptake).

Zinc is available in caplets, capsules, tablets, gums, lozenges and injectable solutions.

• Capsules and tablets are to be swallowed whole with water/liquid, as applicable.
• Gums are to be chewed thoroughly to absorb the zinc through the mucosa in the mouth, as applicable.
• Lozenges are to be placed in your mouth between your gums and your cheek, as applicable.
• Injectable solutions will be administered parenterally, as applicable.

Zinc can be used as a supplement support for bone mineralization.

Zinc supplement supports the immune system, helping the body fight infections and illnesses.

Zinc is essential as a supplement for healthy growth and development, particularly in children and adolescents.

Adequate intake of Zinc supplements may be used to enhance faster healing of wounds, cuts, and ulcers.

Vitamins and natural supplements should not replace a balanced diet.

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

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

• Deficiency: Traditional uses of zinc supplementation include the treatment of defects or their prevention in several diseases, including acrodermatitis enteropathica, anorexia nervosa, malabsorption syndromes, persistent diarrhoea, and others. Also, athletes utilise zinc to make up for sweat-related losses.
• Common cold: Zinc lozenges or syrup can accelerate the recovery from a cold, although the impact on the severity of the symptoms is yet unknown. However, the ideal zinc dose, type, frequency, and duration for treating the common cold should be determined through further research.
• Pneumonia in children: Studies conducted in countries with low incomes indicate that zinc supplementation reduces young children's risk of pneumonia. Zinc doesn't appear to accelerate healing or lessen pneumonia-related mortality.
• HIV in children and adults: Low zinc levels are common in HIV-positive patients. This happens as a result of their inability to absorb zinc from meals. They also have diarrhoea often, which accelerates zinc loss. According to several research, more zinc reduces diarrhoea and HIV implications.
• Childhood diarrhoea: Diarrhoea often kills children in underdeveloped nations. Numerous young children are zinc deficient or otherwise malnourished, and studies suggest that zinc supplementation help shorten the length of diarrhoea in children.
• Age-related macular degeneration (AMD): AMD is an eye condition that slowly impairs vision. In significant trials, older AMD patients who took daily dietary supplements, including zinc and other elements, for five years had a reduced probability of acquiring advanced AMD than those who did not take the supplements. These patients were at a high risk of developing advanced AMD.
• Type 2 diabetes: Low zinc levels are expected in type 2 diabetics. According to some studies, taking zinc supplements may help decrease cholesterol and blood sugar levels. However, further research is required to determine whether zinc supplementation for type 2 diabetics is beneficial.
• Wound healing: Zinc is essential for immune system health and wound healing. In conditions of inadequate nourishment and deficiency-related wound healing, supplements help increase zinc levels. Zinc can be used orally or topically to enhance healing and decrease infection.

Zinc supplementation may be administered orally or parenterally.

• Orally: Zinc supplements are available in tablets, capsules, lozenges and gum and are taken orally. The most effective is when they are taken at least 1 hour before or 2 hours after meals.
• Parenterally: The injectable solution of zinc is administered intravenously or intramuscularly.

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).

• Capsule (zinc gluconate): 50mg
• Capsule (zinc acetate): 25mg, 50mg
• Tablet (zinc gluconate): 15mg, 30mg, 50mg, 100mg
• Tablet extended-release (zinc gluconate): 100mg
• Lozenge (zinc gluconate): 10mg, 13.3mg
• Gum: 13.3mg
• IV solution (zinc sulfate): 1mg/mL, 5mg/mL
• IV solution (zinc chloride): 1mg/mL

Dosage Adjustment for Adult Patients

Common Cold

The dose expressed as elemental zinc

4.5-23.7 mg zinc gluconate lozenge PO q2hr

Wilson Disease

Dose expressed as essential zinc

Zinc acetate (Galzin): 50 mg oral three times daily

During pregnancy: 25 mg oral three times daily which may increase to 50 mg three times daily if inadequate response.

TPN

Acute catabolic state: 4.5 to 6 mg/day added to TPN Intravenously if metabolically stable.

Metabolically stable: 2.5 to 4 mg/day; an additional 12.2 mg per litre of small bowel fluid lost, or 17.1 mg/kg of stool or ileostomy is recommended.

Zinc is available in oral solid dosage forms and parenteral solutions.

Zinc should be used as supplement support for maintaining strong bones along with appropriate dietary restrictions.

• Limit the consumption of drinks that include caffeine, such as coffee, tea, chocolate, and alcoholic beverages, as this substance could hinder zinc absorption.
• Avoid consuming calcium-rich foods like dairy products and soybeans or high-fibre foods like legumes, chai seeds and avocado, as it may interfere with Zinc absorption.
• Stay within your daily calorie needs.

The dietary restriction should be individualised as per patient requirements.

Recommended Daily Allowance (RDA)

The RDA for adults is 11 mg/day for women and 8 mg/ day for men.

Upper Tolerable Intake (UTL):

The UTL for adults is 40 mg/day.

Zinc supplementation may be contraindicated under the following conditions:-

• Hypersensitivity or allergy to zinc.
• Individuals with certain medical conditions, such as kidney disorders, Wilson's disease, or hemochromatosis, should avoid zinc as it might worsen the situation.
• Autoimmune disorders like rheumatoid arthritis, may be affected by zinc supplementation.
• Bariatric surgery reduces zinc absorption and might increase the risk of zinc deficiency.
• In open or broken skin, zinc supplements should be avoided as they may cause burning, stinging, itching, and tingling.

The treating healthcare must closely keep a watch and monitor for signs and symptoms such as GI disturbances or allergies. It is recommended to discontinue zinc in case of such reactions.

Intake of lower zinc in the diet might increase the risk of getting kidney disease

It is advised not to inhale zinc through the nose as it may lead to permanent loss of smell.

Caution is advised when consuming alcohol with zinc.

Safe to use during breastfeeding.

Safe to use during pregnancy.

Zinc is generally well-tolerated.

The adverse reactions related to zinc can be categorised as-

• Common: Stomach cramps, nausea or vomiting and diarrhoea.
• Less Common: Headache, fatigue and metallic taste in the mouth.
• Rare: Copper deficiency, neurologic deterioration, anaemia and reduced immune function.

The clinically relevant drug interactions of zinc are briefly summarized here:

• Calcium: Separate dosages by two hours; high dietary calcium levels reduce zinc absorption in animals, and it is unclear in the case of humans.
• Angiotensin-II receptor blockers and thiazide diuretics: These drugs reduce zinc status, most likely due to increased zinc excretion from the urine. In conjunction with long-term medication therapy, increased zinc consumption may be necessary.
• Coffee: Coffee reduces the absorption of zinc — separate intakes by 2 hours.
• Copper: High zinc intakes (100–150 mg/day) may interfere with copper metabolism and can lead to hypocuprinaemia with long-term use. Avoid using high-dose zinc supplements long-term, or increase the intake of copper.
• Folate: Folate intake may lower zinc levels — observe for any signs and symptoms of zinc deficiency with long-term folate supplementation.
• Iron: Supplemental (38–65 mg/day elemental) iron lowers zinc absorption— separate doses by 2 hours.
• Non-steroidal anti-inflammatory drugs: Zinc interacts with non-steroidal anti-inflammatory drugs by forming complexes with these drugs— separate dose by 2 hours.
• Tetracyclines and quinolones: Complex formation between zinc and tetracycline results in decrease absorption of both substances with a potential reduction in efficacy — separate dose by 2 hours.
• Thiazide and loop diuretics: These diuretics cause high urinary zinc loss —with long-term use, monitor for signs and symptoms of zinc deficiency. Increasing the intake of zinc may be beneficial with long-term therapy.
• Methylphenidate: The efficacy of this drug is enhanced by supplementation with zinc sulfate (15 mg zinc) for 6 weeks in children with ADHD.
• Radiotherapy: Radiotherapy lowers plasma zinc levels. Intensive radiotherapy treatment may require zinc supplementation
• Interferon-alpha/ribavirin: Zinc supplementation does not affect Interferon-alpha and ribavirin treatment for hepatitis C patients.
• Antidepressants: Zinc supplementation (25 mg elemental zinc daily) enhances the efficacy of antidepressants like Tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors (SSRIs) after 2 weeks of intervention.

The common side of zinc includes the following:

• Nausea and vomiting
• Diarrhoea
• Stomach cramps
• Headache
• Reduced copper absorption leads to copper deficiency
• Anaemia
• Impaired immune function in excessive doses
• Metal taste in the mouth

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

• Pregnancy:

Pregnancy category: A

The use of zinc during pregnancy is generally acceptable, and clinical studies have shown no evidence of fetal risk. Zinc is safe in pregnancy and may enhance fetal heart rate in zinc-deficient mothers

The RDA for Zinc in pregnant between the age of 14-18 years is 12 mg/day, and for age between 18-50 years is 11 mg/day.

• Paediatrics:

Zinc is essential for maintaining bone health in the pediatric population

Zinc supplements are the best way to help children get enough daily zinc.

The RDA for Zinc in paediatrics ranges from 8-11 mg/day.

Dosage Adjustment for Paediatric Patients

Total Parenteral Nutrition (TPN)

Less than 5 years: 100 mcg/kg/day added to TPN Intravenously

Premature infants (more than 1500 g birth weight to 3 kg): 300 mcg/kg/day added to TPN Intravenously.

Wilson's Disease

Zinc acetate

More than 10 years: 25 mg oral three times daily which may increase to 50 mg three times daily if inadequate response.

• Geriatrics:

Zinc helps in the prevention of infection and the maintenance of the immune system in the elderly. It is required as a nutrient for the elderly to have a good quality of life.

The RDA for zinc in geriatrics is 8-11 mg.

• Lactating mothers:

The use of zinc during breastfeeding is generally acceptable, and clinical studies have shown no evidence of fetal risk.

The RDA for Zinc in lactating is 12 to 13 mg.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge about the identification and treatment of overdosage of zinc. Overdosing on zinc supplements can cause hypercalcemia, which can cause symptoms like constipation, nausea, vomiting, and kidney stones.

There is no specific antidote or treatment for excessive intake of supplemental zinc. When an overdose is suspected, zinc should be terminated immediately and increasing fluid intake. Supportive treatment should also be given, along with addressing any symptoms that persist or worsen. Physical therapy might be added if necessary.

Biochemistry profile of zinc:

Zinc exists predominantly as Zn2+, where it works as a cofactor for enzymes, providing critical catalytic actions. It impacts several biochemical pathways, including DNA and RNA synthesis, protein synthesis, cell signalling, immunological response, and antioxidant defence. Zinc is essential for protein structure maintenance, folding, and structural integrity.

As a cofactor, zinc catalyses essential events in cellular metabolism, gene expression, and immunological response. It functions in cell signalling, influencing hormone and neurotransmitter responses, and works as an antioxidant, protecting cells from oxidative damage.

Kinetic profile:

• Absorption: Zinc absorption occurs predominantly in the small intestine, particularly in the duodenum and jejunum. It is a complicated process that includes both carrier-mediated transport and passive diffusion. Dietary zinc levels, body zinc status, and other dietary components can all influence zinc absorption.
• Distribution: Zinc interacts with plasma proteins and is distributed throughout the body via blood circulation after absorption. It is found in various tissues, with large quantities in the liver, muscles, bones, and brain.
• Metabolism: Zinc is involved in numerous metabolic pathways and is a cofactor for over 300 enzymes. It helps generate DNA, protein, immunological function, and antioxidant protection. Zinc is also required for healthy growth, development, and wound healing.
• Elimination: Zinc is largely excreted in the gastrointestinal tract, primarily in the faeces. The liver controls zinc excretion into the bile, which is eventually excreted from the body via faeces. A lesser amount of zinc is eliminated in urine and through skin shedding.

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