What is it?

Description

Zinc is an essential micronutrient that binds to approximately 2,800 human proteins for catabolic, structural, and regulatory functions. (102) It is involved as a signaling molecule in a vast number of physiological processes and plays a structural role in 10% of all mammalian proteins. It acts as a regulator of gene expression and homeostasis, as well as an anti-inflammatory and anti-oxidative agent. (6)(139) Zinc plays important roles in the growth and health of connective tissues (e.g., bone, hair, skin, tendons, skin), the nervous system, cognition, and immunity. (12)(131)  

Low zinc levels may be associated with various auto-immune disorders, (32)(101)(137)(153) cardiovascular disorders, (71)(97)(175) cognitive and neurodegenerative disorders, (11)(23)(134)(152)(155) connective tissue disorders such as acne (171) and osteoporosis, (29) endocrine disorders including polycystic ovarian syndrome (1) and type II diabetes, (56) and male infertility (176) and prostatitis. (36) 

High levels of exercise, (34) vegetarian diets, and the use of anti-hypertensive medications (22) may lead to low zinc status, and thus supplementation or fortification may be required. (58) The recommended intakes of elemental zinc from the diet are approximately 11 mg for adult males and 8 mg for females, (111) though daily pharmacological doses are much higher, often ranging between 30 to 150 mg. (139) It should be noted that excess intake of zinc may lead to copper deficiencies, (104) making it important for clinicians to be aware of how to recommend zinc for short-term therapeutic purposes versus for maintaining zinc levels.

Please note that this review focuses on the provision of zinc in oral supplementation forms only. Dosing and administration are provided below using the elemental amount of zinc found in supplements and not the total weight of a zinc compound.

For a review of the applications of topical zinc in dermatology, please see Zinc Therapy in Dermatology: A Review. (67)

Main uses

Antioxidation, anti-inflammation
Cardiometabolic health
Immune health, common cold, and infection
Depression
Pediatric diarrhea
Prenatal support and growth
Skin, mucosal lining, and wound healing

Formulations

Form
Characteristics
Zinc bisglycinate
Contains 31% elemental zinc
Zinc bisglycinate was 43.4% more bioavailable than zinc gluconate (61)
Zinc acetate
Contains 30% elemental zinc
Zinc acetate was 43% more bioavailable than zinc oxide and more than 5.8x more bioavailable in states of hypochloridia (75)
Possesses strong astringent taste (163)
Zinc citrate
Contains 34% elemental zinc
Provided equal bioavailability to zinc gluconate, (15) but without the astringent taste and odor, and at a cheaper price. Zinc citrate had a 11% greater absorption than zinc oxide (163)
Zinc picolinate
Contains 21% elemental zinc
Provided greater absorption than zinc citrate or zinc gluconate, but serum zinc did not rise significantly (15)
Zinc gluconate
Contains 14% elemental zinc
Provides equal bioavailability to zinc citrate, (15) but may possess an astringent taste and be higher priced (due to low elemental zinc content)
Zinc gluconate had 8-11% greater absorption than zinc oxide (146)(163)
Zinc methionine
Contains 18% elemental zinc
Zinc methionine was 25% more bioavailable than zinc sulfate (132)
Zinc sulfate
Contains 23% elemental zinc
Zinc sulfate was 26% more bioavailable than zinc oxide (167)
Possesses strong astringent taste, but is inexpensive (163)
Zinc ascorbate
Contains 16% elemental zinc
Zinc ascorbate was equally bioavailable to zinc sulfate (132)
Zinc oxide
Contains 80% elemental zinc
Very low cost, but least absorbable with -11% difference compared to zinc citrate or gluconate (163)
Zinc carnosine
Contains 23% elemental zinc
Also known as Polaprezinc
Zinc aspartate
Contains 20% elemental zinc

Dosing & administration

Adverse effects

The proportion of individuals reporting adverse events from zinc supplementation may be higher in treatment groups than placebos (24-58% higher risk). This may include higher risk for experiencing bad taste (65-130%) and nausea (64-115%), but no difference for abdominal pain, constipation, diarrhea, dry mouth, or oral irritation compared to placebo was reported. (143)(147)(171) However, the use of zinc supplements at normal therapeutic doses is unlikely to cause any long-term harm. (72) In children requiring supplementation for diarrhea reduction, zinc may increase the risk of vomiting (20-94%). (60)(93)(96)(105) Zinc gluconate produced a higher frequency of vomiting than zinc sulfate or acetate in one analysis. (100)

Zinc may reduce copper retention (57) and iron absorption. (116)(117) For copper, case reports of zinc-induced copper deficiencies exist at excessively high doses (e.g., 120-180 mg over seven months to an infant, or up to 600 mg per day in adults). (19)(166) Lower level dosing does not seem to impact copper status. (17)(85)(140)(169) For iron, even modest doses of zinc can reduce iron status. (27)(43)(49) However, the risk for anemia as a result of these micronutrient deficiencies does not appear to increase between zinc doses of 10-20 mg for up to 15 months. (46)

Pharmacokinetics

Absorption

  • Between 26-34% of ingested zinc is absorbed in the small intestine (duodenum and jejunum) via transporters, including Zrt-, Irt-like protein 4 (ZIP4), and zinc transporter 1 (ZnT-1), and via passive diffusion (at high concentrations) (102)(131)
  • Aqueous zinc solutions may be better absorbed (60-70%) than solid foods (102)(131)
  • Zinc may be more efficiently absorbed in states in which greater amounts of zinc are required, such as in states of deficiency, pregnancy and lactation, and infancy (102)(131)
  • Nutritional factors such as the presence of animal proteins or citrate improve absorption, whereas reduced absorption may occur with ingestion of phytate (reduced absorption 45%; found in plant seeds, grains, and legumes), fiber, calcium, and iron (16)(102)(131)

Distribution

  • Post-absorption, zinc is moved into circulation and bound to albumin (60-70%), α-macroglobulin (30%), and transferrin (10%) for transport to various tissues (102)(131)
  • The human body contains approximately 2.6 g of zinc, found in skeletal muscle (50-57%), bone (29-36%), skin (4-6%), liver (3-5%), blood (1.5%), intestines (1.2%), brain (0.6-1.5%), kidneys (0.6-0.7%), lung (0.5%), stomach (0.5%), heart (0.3%), hair and nails (0.1-0.5%), spleen (0.1%), and eyes (<0.01%); however, this is not indicative of biological activity at these sites (102)(139)
  • For example, seminal plasma contains relatively very little zinc (0.08-0.27 mg/mL), but zinc is known to benefit various sperm parameters (48)(139)

Metabolism

  • Homeostatic balance is achieved via quick adjustments to zinc absorption or excretion depending on states of deficiency or excess (102)(131)
  • Intracellularly, zinc is bound to metallothionein proteins, which act as a reservoir to release zinc when needed and prevent cellular toxicity from an excessive presence of zinc (12)
  • Zinc may be removed from the tightly regulated intracellular environment by other ZIP and ZnT transporters (102)

Excretion

  • Approximately 50% of zinc is excreted into the feces (6.0-22.4 mg/day) via biliary and intestinal secretions (131)
  • However, zinc can be excreted in the urine (0.3-6.5 mg/day) or via losses of skin (0.29-0.67 mg/day), hair (30 mcg/day), semen (0.09-0.63 mg/day), menstruation (0.4-0.6 mcg/day), or sweat (0.5 mg/day) (16)(131)
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