Each review contains information about the ingredient’s clinical applications, formulations, dosing & administration, adverse effects, and pharmacokinetics. Learn more about our critical appraisal research or contact us for initial guidance and more information.

Zinc

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

Acne vulgaris
General outcomes from A-level evidence	↓ number of acne papules (moderate to large effect, SMD=0.73-0.82) within the first 12 weeks using oral or topical formulations compared to placebo, with ~ 2.8 better odds of clinical improvement; however, oral zinc may be more effective (3.5 better odds) (171) Note: Zinc may provide benefit via anti-bacterial and anti-inflammatory properties and through reduced sebum production (20)
Dosing & administration	50-140 mg (from zinc sulfate) per day for 6-12 weeks
Outcomes	↓ acne score slightly more than placebo (65) ↓ number of papules, infiltrates, and cysts compared to placebo (156) Note: A greater proportion of Px and clinicians indicated subjective improvement by 12 weeks compared to placebo (76)
Class of evidence	B
Dosing & administration	30 mg (from zinc gluconate) per day for three months
Outcomes	↓ inflammatory score compared to placebo (50) Achieved more than ⅔ decrease in lesions in 31% of Px Note: Zinc gluconate was not as effective as 100 mg of minocycline (17% superiority after three months) (51)
Class of evidence	C

Antioxidative, immune, anti-inflammatory profile
General outcomes from A-level evidence	↑ total antioxidative capacity (225.96 mmol/L), GSH (49.99 μmol/L), (110) & SOD (357.57 U/gHb) in hemodialysis, (159) CD4 cells (large effect, SMD= 1.11), & IL-2 (2.96 pg/ml); (54)(81) ↓ MDA (0.42-0.49 μmol/L) (78)(110) & in hemodialysis (1.275 μmol/L), (159) neutrophil levels (small effect, SMD= 0.46), CRP (0.92-2.81 mg/L), hs-CRP (0.52 mg/L), TNF-ɑ (0.49-8.22 pg/ml), & IL-6 (0.76-3.15 pg/ml) (54)(78)(81)(109) Note: No effects were observed on nitric oxide levels, (110) white blood cells, lymphocytes, monocytes, CD3 levels, (81) or TNF-ɑ. (54)
Dosing & administration	Up to 40-50 mg per day
Outcomes	↓ CRP (~1.0 mg/L) with the greatest efficacy when the dose is 50 mg (1.97 mg/L), (109) IL-6 (0.76 pg/ml), & TNF-ɑ (0.37 pg/ml) ↑ IL-2 (2.96 pg/ml) Note: While doses higher than 40 mg may further reduce IL-6, this was shown to increase TNF-ɑ, thus providing the better indication for lower dose therapy (54)
Class of evidence	A
Dosing & administration	30-45 mg (from zinc gluconate) per day for 2-12 months to adults
Outcomes	↑ T-cells (30%), (14) IL-mRNA (62%), & total antioxidative capacity (17-24%) ↓ TNF-ɑ (48%), hs-CRP (24-36%), IL-6 (24-78%), MCP-1 (11%), secretory phospholipase A2 (30%), sVCAM-1 (11%), sE-selectin (10%), MDA (21-23%), & 8-OHdG (26%) (13)(82)(90) Note: The incidence of infections was 79% lower with zinc compared to placebo (126)
Class of evidence	B
Dosing & administration	20 mg (from zinc carnosine) per day for 12 weeks to older adults with zinc deficiency
Outcomes	↑ SOD activity (33%) compared to placebo ↓ DNA damage (24%) (144)
Class of evidence	B
Dosing & administration	7-10 mg (from zinc gluconate) per day for 3-9 months to children with or at risk of nutritional deficiency
Outcomes	lymphocyte concentration (11%) & eosinophils (~45%) compared to placebo (87) ↑ rise in T cells (25%), helper T cells (64%) & helper T: suppressor T cell ratio (73%) compared to control (140)
Class of evidence	B

Attention-deficit hyperactivity disorder (ADHD)
General outcomes from A-level evidence	Note: There is little support for the use of zinc to manage pediatric ADHD (64)(70)
Dosing & administration	40 mg (from zinc sulfate) per day for 12 weeks to children with ADHD
Outcomes	↓ total ADHDS score (~100%) compared to placebo, which was driven by improvement in hyperactive, impulsive, and impaired socialization subscores Note: However, there was no greater benefit in full therapeutic response rates between zinc and placebo (18)
Class of evidence	B
Dosing & administration	15 mg (from zinc sulfate) per day for six weeks adjunct to methylphenidate to children with ADHD
Outcomes	↑ parent and teacher’s impression of improvement scores compared to methylphenidate alone (4)
Class of evidence	C

Cancer therapy support
General outcomes from A-level evidence	↓ risk (29%), (45) severity (large effect, SMD= 0.89), (31) and duration of oral mucositis, & oral pain and dry mouth caused by radiotherapy or chemoradiotherapy, but not chemotherapy alone in the majority of studies (77) ↓ risk of radiation-induced dysgeusia (28%), but whether it improves taste acuity post-radiotherapy is less certain (21)(33) Note: Zinc may not reduce the risk of radiation-induced oral mucositis or its severity (145)
Dosing & administration	45 mg (from zinc sulfate) three times per day at the start of radiation therapy for four weeks to Px with head and neck cancer
Outcomes	↓ risk of radiation-induced dysgeusia (28%) (33)
Class of evidence	A
Dosing & administration	50 mg (from zinc sulfate) three times per day for two weeks or until the end of chemotherapy starting on the first day of chemotherapy to Px with cancer
Outcomes	↓ incidence of oral mucositis (2.1x lower), severity (56-84%), (127) & xerostomia (8)
Class of evidence	B
Dosing & administration	50 mg (from zinc sulfate) three times per day for 6-8 weeks starting on the first day of radiotherapy to Px with head and neck cancer
Outcomes	↓ incidence of oral mucositis (92%) (53) & may delay/reduce the severity of mucositis and dermatitis (98)
Class of evidence	B

Cardiometabolic profile
General outcomes from A-level evidence	Improves glycemic control via: (44) ↓ glycemic index (moderate effect, SMD= 0.65), FBG (8.82-19.69 mg/dl, moderate effect, SMD= 0.52), 2-h postprandial glucose (34.87-39.87 mg/dl), insulin resistance (0.46-0.87), HbA1C (0.35-0.54%, moderate effect, SMD= 0.65), and hs-CRP (1.63 mg/L) across various states of health including obesity, pre-diabetes, type II diabetes, or in Px who are generally considered as healthy (26)(35)(83)(124)(161) ↓ lipid profile (small effect, SMD= 0.41), triglycerides (10.92-25.68 mg/dl, moderate effect, 0.66), total cholesterol (10.92-32.37 mg/dl, moderate effect, SMD=0.65), LDL (6.87-11.19 mg/dl) and VLDL (large effect, SMD= 1.59) across various states of health, including obesity, pre-diabetes, type II diabetes, or in Px who are generally considered as healthy (9)(83)(88)(124)(128) Note: Individual analyses may also show no difference in insulin, (161) insulin resistance, TGs, total cholesterol, LDL, HDL, SBP, DBP, and anthropometric indices (weight, BMI, or WC). (52)(59)(88)(128) Effectiveness may be related to the level and duration of the dose. (9)(124)
Dosing & administration	Up to 25 mg per day for a minimum of 12 weeks in Px with varying health statuses, including obesity, type II diabetes, pre-diabetes, gestational diabetes, or in Px who are generally considered healthy
Outcomes	↓ FBG (18-19 mg/dl), insulin resistance (0.63), TGs (19-25 mg/dl), total cholesterol (11-13 mg/dl), & LDL (8.5-11 mg/dl) Note: Higher doses and shorter durations may still provide benefit for factors such as HbA1C, insulin resistance, or TGs, but lower dosing for longer durations seems to improve more risk factors (124)
Class of evidence	A
Dosing & administration	Up to 100 mg per day for up to 12 weeks to Px with type II diabetes
Outcomes	↓ TGs (17.08 mg/dl) & total cholesterol (26.16 mg/dl) Note: Short-term (<12 weeks) may improve TGs (~33 mg/dl) and total cholesterol (~43 mg/dl) to the greatest extent, as well as provide improvements in LDL-C (~27 mg/dl), but longer durations (>12 weeks) may begin to attenuate in efficacy. (9)
Class of evidence	A
Dosing & administration	30 mg (from zinc gluconate) per day for six weeks to women with gestational diabetes
Outcomes	↓ FBG (~7.2 mg), insulin (7.9 μIU/mL), insulin resistance (two points), beta-cell function (27.2 points), insulin sensitivity (0.02 points), TGs (32.3 mg/dL), & VLDL (6.5 mg/dL) differences compared to placebo (86)
Class of evidence	B

Common cold and other respiratory tract infections
General outcomes from A-level evidence	Common cold: ↓ duration of colds (~1.5-3.0 days), common cold symptoms (59%), specifically cough (1.73 days, 46%), nasal congestion (0.7 days, 37%) and drainage (1 day, 34%), sore throat (0.46 days, 18%), scratchy throat (33%), hoarseness (43%), sneezing (22%), and muscle soreness (54%), especially using zinc acetate lozenges, (2)(72)(73)(74)(160) risk of symptom persistence by day seven (37-55%), likelihood of developing a subsequent cold, (147) & symptom severity (medium effect, SMD= 0.67) (143) Note: Intranasal zinc administration did not reduce cold symptoms within three days (38) Respiratory tract infections: ↓ duration of acute RTI symptoms in adults (47%), (2) incidence of acute lower RTIs in children (20-35%), pneumonia (13-21%) in infants aged 2-59 months or children younger than five years of age (19%), & risk of severe pneumonia mortality (57%) (3)(95)(133)(170)(158) Note: There was no reduction in risk of acute RTIs in adults, (2) and individual analyses may indicate lack of effectiveness in infants or children with pneumonia, with no improvement in symptoms, time to recovery, or mortality, (25)(170) and no improvement in the efficacy of standard antibiotics for pneumonia. (69)(154)(158)
Dosing & administration	75-80 mg (from zinc acetate in particular or gluconate as lozenges or syrup) in divided doses every 2-3 hours per day starting within 24 hours of onset and throughout the duration of the cold or for two weeks
Outcomes	↓ duration of cold (~1-3 days), cough (1.73 days, 46%), nasal congestion (0.7 days, 37%) and drainage (one day, 34%), sore throat (0.46 days, 18%), scratchy throat (33%), hoarseness (43%), sneezing (22%), muscle soreness (54%), likelihood of persisting symptoms by day seven (55%), & likelihood of developing subsequent cold (36%) (72)(73)(74)(147)
Class of evidence	A
Dosing & administration	13-23 mg every 2-3 hours to adults throughout the duration of the acute RTI
Outcomes	↓ duration of acute RTI symptoms by 47% & common cold symptoms by 59% in adults Note: Supplementation did not reduce the risk of acute RTIs in adults (2)
Class of evidence	A
Dosing & administration	10-20 mg per day for for up to 18 months to children in developing countries under five years of age
Outcomes	↓ incidence of acute lower RTIs (35%) (133)(170) & pneumonia (19%)
Class of evidence	A

Depression
General outcomes from A-level evidence	↓ depression scores (4.15 points) as solo therapy compared to control, while the highest levels of zinc intake reduced the risk for depression by 28% (172) ↓ depression scores (small to moderate effect, SMD = 0.36-0.66) as adjunct therapy compared to placebo (39)(92)(142)
Dosing & administration	25-30 mg per day for 8-12 weeks to Px with depression
Outcomes	↓ depression scores (4.15 points) as solo therapy in Px with scores initially between 20-30 points (172)
Class of evidence	A
Dosing & administration	Up to 25 mg per day for 6-12 weeks to Px with depression using antidepressants
Outcomes	↓ depression scores (small to moderate effect, SMD = 0.36-0.66) as adjunct therapy compared to placebo (39)(142)
Class of evidence	A
Dosing & administration	25 mg (from zinc sulfate) per day for 12 weeks to Px with major depression using SSRIs or tricyclic antidepressants
Outcomes	↓ depression scores (1.5-3x) compared to antidepressants plus placebo (114)(129) Improves the efficacy of imipramine in treatment-resistant depression only (148)
Class of evidence	B
Dosing & administration	30 mg (from zinc gluconate) per day for 12 weeks to obese Px with mild to moderate depressive symptoms
Outcomes	↓ depression score (37-43%) compared to placebo (173) Note: May increase BDNF (37%), but this may depend on higher baseline depressive scores (149)
Class of evidence	B
Dosing & administration	50 mg (from zinc sulfate) per day for 12 weeks to Px with multiple sclerosis with moderate to severe depression
Outcomes	↓ depression score (26%) compared to baseline, but no change in placebo (135)
Class of evidence	B

Diarrhea prevention (pediatric)
General outcomes from A-level evidence	↓ risk of diarrhea (9-20%) (105)(170)(and multiple diarrheal episodes (15-30%), (3)(122) duration of diarrhea (11.5-20 hours) (177) and persistent diarrhea ~16 hours), number of children with diarrhea for three (22-30%), five (24%), and seven days (18-39%), & risk of mortality (23%), particularly in children with malnutrition (60)(93)(96)(123)(157) Note: Individual analyses show no reduction in diarrhea-related mortality in children (170) Supplementation may increase the likelihood of vomiting (54-57%) and may only be effective in children older than six months of age or who are malnourished (60)(96)
Dosing & administration	Up to 20 mg per day for two weeks to children with diarrhea
Outcomes	↓ duration of diarrhea (~11.5 hours) and persistent diarrhea (~16 hours), number of children with diarrhea for three (23%), five (24%), and seven days (18%), particularly in children with malnutrition Note: Zinc may not be effective in children younger than six months of age (96)
Class of evidence	A
Dosing & administration	10-20 mg per day for up to 18 months to children younger than the age of five in developing countries
Outcomes	↓ incidence of diarrhea (13%) (170)
Class of evidence	A
Dosing & administration	5-10 mg per day for two weeks to children between the ages of 6-59 months in low- to middle-income settings
Outcomes	↓ proportion of children with diarrhea by day five to the same extent as 20 mg doses Note: Despite the equivalent efficacy of 5-10 mg to 20 mg, there was a reduced risk of vomiting (19-29%) in the lower dose group compared to the higher dose group, possibly indicating cause to re-evaluate the need for higher doses suggested by older analyses (47)
Class of evidence	B

Fertility (male)
General outcomes from A-level evidence	↓ semen volume (large effect, SMD = 0.99), sperm concentration (1.48×10^6 spz/ml, large effect, SMD= 3.25), sperm count (large effect, SMD= 4.95) & sperm motility (7.03%, large effect, SMD= 1.82), & percentage of normal sperm morphology (moderate effect, SMD= 0.75) (136)(138)(176)
Dosing & administration	50 mg (from zinc sulfate) twice per day for 1-4 months to males with infertility
Outcomes	↓ sperm count (11 x10^6 spz/mL averaged across trials) Note: Individual studies found within this review show improvement in other semen parameters, including semen volume, motility, and normal sperm form percentage (138)
Class of evidence	A
Dosing & administration	66 mg (zinc sulfate) per day for six months to infertile or subfertile men
Outcomes	Improves sperm morphology (33%) post varicocelectomy in infertile men (10) & sperm concentration in subfertile men (168)
Class of evidence	B
Dosing & administration	46-57.5 mg (from zinc sulfate) twice per day for three months to males with asthenozoospermia or oligozoospermia
Outcomes	↑ difference in sperm count (10.5%), progressive motility (6-8%), sperm membrane integrity (12.8-47%). immobile sperm (11.9%), antisperm antibodies (12.2%), sperm IL-4 (9.7%), total antioxidative capacity (4x), & Zn-Cu SOD (5x) compared to control ↓ MDA (60%), TNF-ɑ (79%), & sperm DNA fragmentation compared to control (118)(119)
Class of evidence	C

Growth and development
General outcomes from A-level evidence	↑ height (0.23-0.37 cm), weight (0.14-.23 kg), and weight for age score after birth, with greater effects on height (1.37 cm) and height for age score by age of two Note: Overall, there may only be small improvements (with questionable clinical relevance) in height and weight that persist up to the age of 12, though effects may only be important in children at risk of low zinc levels older than the age of two. (24)(63)(80)(99)(105)(112)(130) Some evidence suggests small benefits on weight for age and weight for length (SMD= ~0.15) in infants less than six months of age. (94) No effects are observed on risk of growth stunting, being underweight, or wasting. (63)(99) Other analyses show no benefit at all. (84)(151)
Dosing & administration	Up to 20 mg per day for up to 15 months to infants older than six months and up to 12 years of age at risk for nutritional deficiencies
Outcomes	↑ height (small effect, SMD= 0.35) & weight (small effect, SMD= 0.31) (24) Note: Use of 10 mg per day for 24 weeks produced the greatest increases in growth for children under the age of five (0.37 cm), although any dose within this range was beneficial (small effect, SMD= 0.13) (80)
Class of evidence	A
Dosing & administration	5-10 mg per day for six months to infants starting at birth
Outcomes	↑ weight for age and weight for length (small effect, SMD= ~0.15) by six months of age (94)
Class of evidence	A

Postoperative sore throat
General outcomes from A-level evidence	No data currently available.
Dosing & administration	40 mg (from a zinc sulfate lozenge) 30 minutes prior to Px requiring surgery with endotracheal intubation
Outcomes	↓ incidence of postoperative sore throat (58%) & severity of mild sore throat (55)
Class of evidence	B

Prenatal support
General outcomes from A-level evidence	↓ risk of preterm birth (14%), (30) particularly in women with low zinc or nutritional status (121) Note: Maternal supplementation did not reduce likelihood of low birthweight infants, stillbirth, child development, or maternal outcomes such as pre-eclampsia (30)(62)(66)(99)(121)
Dosing & administration	Up to 50 mg per day during pregnancy
Outcomes	↓ risk of preterm birth (14%) (30)
Class of evidence	A
Dosing & administration	15-30 mg (from zinc sulfate) per day to pregnant women with or at risk of low zinc status throughout pregnancy
Outcomes	↓ risk of preterm labor and stillbirth (88%), prolonged labor (57%), (113) incidence of infant acute diarrhea (16%), dysentery (64%), & impetigo (47-54%) at six months of age (41)(120) ↑ weight (0.54 kg), calf-circumference (1.01 cm), chest circumference (0.60 cm) of infants by four months of age, (79) & femur diaphysis length and neurobehavioral development in fetuses (106)(107)
Class of evidence	B
Dosing & administration	50 mg (from zinc sulfate) per day until delivery to pregnant women with a previous preterm delivery
Outcomes	↑ birth head circumference (1.3 cm) compared to placebo, with non-statistically significant increase in gestational age and birth weight at delivery (40)
Class of evidence	B
Dosing & administration	20 mg (from zinc sulfate) per day until delivery to pregnant adolescents at risk of nutritional deficiency
Outcomes	↓ proportion of low birthweight births (67%) and prematurity (52%) compared to placebo ↑ birth weight (79 g) of infants from mother less than 16 years old (28)
Class of evidence	B

Wilson disease
General outcomes from A-level evidence	Provides positive clinical effect in 100% of presymptomatic, 55% of hepatic, & 90% of neurological symptoms, and appears to be as equally effective as D-penicillamine Note: There may not be enough evidence to claim efficacy superiority of popular treatments for Wilson disease (such D-penicillamine), but zinc may exhibit a better safety profile (7)(164)
Dosing & administration	50-150 mg (typical dosing, divided throughout the day) per day ongoing to Px with Wilson disease
Outcomes	Provides positive clinical effect in 100% of pre-symptomatic, 55% of hepatic, & 90% of neurological symptoms, and appears to be as equally effective as D-penicillamine but with a better safety profile Note: Zinc is recommended as maintenance therapy owing to its ability to reduce copper absorption, slowly producing a negative copper balance (<1 mg per day). (164) It is important to note that evidence is primarily based on long-term observational trials with no comparison groups
Class of evidence	A
Dosing & administration	140-185 mg (from zinc sulfate) per day ongoing to Px with Wilson disease
Outcomes	Px were 100% asymptomatic in the preclinical stage, while 83% who were symptomatic became asymptomatic Note: Zinc sulfate was equally as effective as D-penicillamine, but more Px switched to zinc therapy due to lower incidence of side effects (37)
Class of evidence	C

Wound healing and trauma
General outcomes from A-level evidence	↑ healing rate of pressure injuries (44%) compared to control using diet, supplements, or topical zincs (150) ↓ time to heal burn injuries by ~five days (but without statistical significance) (91) Note: Oral zinc supplementation was not associated with reduced mortality from burn injuries (91) and did not improve healing of arterial and venous leg ulcers in some analyses (115)(165)
Dosing & administration	50 mg (from zinc sulfate) per day for 12 weeks to Px with diabetic foot ulcers
Outcomes	↓ diabetic foot ulcer length (67%) & width (75%) compared to placebo Note: Benefits on glycemic control and antioxidative capacity were also noted (108)
Class of evidence	B
Dosing & administration	120 mg (from zinc sulfate) per day for 15 days to Px with severe head trauma
Outcomes	Improved neurologic recovery (measured by Glasgow Coma Scale) score (19-31%) & Sequential Organ Failure Assessment score (26%) compared to placebo ↓ CRP (52%) & erythrocyte sedimentation rate (10%) compared to baseline, but placebo increased in these inflammatory factors, attenuated rise in white blood cells (23%), & reduced number of days in hospital by 13 days compared to placebo (89)
Class of evidence	B
Dosing & administration	12-22 mg (from zinc sulfate or gluconate) per day for one month to Px with severe closed head injury
Outcomes	Improved neurologic recovery (measured by Glasgow Coma Scale) by day 15-21 & reduced deaths (14%) by one-month compared to placebo (174)
Class of evidence	B
Dosing & administration	35 mg (from polaprezinc) per day for four weeks to Px with aspirin-induced small bowel injury
Outcomes	↓ median number of erosions (from two to zero) & reddened lesions (from three to one), but control did not change (162) Note: Zinc carnosine was also shown to prevent increases in intestinal permeability in healthy volunteers (42)(103)
Class of evidence	C
Dosing & administration	50 mg (from zinc sulfate) three times per day throughout the period of wound repair after excision of pilonidal-sinus tracts
Outcomes	↑ rate of healing (~3x) with ~35 fewer days required for healing Large wounds healed 43% sooner with zinc compared to control (125)
Class of evidence	C
Dosing & administration	15 mg (from zinc sulfate) per day adjunct to standard topical therapies until hospital discharge to Px with burns
Outcomes	↓ burn mortality (7%) compared to control Note: Non-significant reductions in healing time & incidence of eschar formation compared to control and increased GSH status compared to baseline were also noted. (5)
Class of evidence	C

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)