Zinc may help diarrhea and dysgeusia; studies are mixed on colds.

[DFM ] Letter Key

Description

Zinc is an essential trace element.

Food Sources

Meats, shellfish, whole grains, seeds, nuts, legumes, vegetables, eggs, and milk

Mechanism/Pharmacokinetics

• Zinc is a cofactor for more than 200 enzymes, including alcohol dehydrogenase, carbonic anhydrase, and carboxypeptidase (1). Zinc is needed in biomembranes, for binding transcription factors, and for stabilizing some hormone-receptor complexes (2).
• The human body contains 1.4 to 2.5 g zinc, mostly in bone and muscle; the highest concentrations are in skin, hair, nails, retina, and testes (3). Twenty percent to 30% of dietary zinc is absorbed intestinally, most is excreted via bile; 2% to 10% is found in urine (2). The average American consumes 10 mg zinc/day.

[Outline]

• DDescription
• FFood Sources
• MMechanism/Pharmacokinetics

[C ] Letter Key

Clinical Trials

• Colds
  • A meta-analysis of eight placebo-controlled randomized controlled trials (RCTs) found no significant effect of zinc on symptoms at 7 days (4). A review of eight double-blind placebo-controlled trials found trials evenly split; neither of the two small trials that looked at incidence of infection after nasal inoculation of rhinovirus found a benefit (5).
  • A double-blind, placebo-controlled trial of 213 participants with cold symptoms found that zinc gluconate nasal gel, applied four times daily until symptoms resolved, significantly shortened duration of symptoms (2.3 ± 0.9 days, compared with 9.0 ± 2.5 days in the placebo group) (6).
• Taste and smell
  • A placebo-controlled RCT in 18 patients receiving head and neck radiation tested zinc sulfate (45 mg t.i.d., from the onset of taste alterations to 1 month after radiation ended) (7). Placebo-treated patients had greater worsening of taste acuity and had slower recovery of taste acuity than zinc-treated patients.
  • An earlier double-blind crossover trial found no benefit of zinc 100 mg/day for hypogeusia (decreased taste) of various etiologies in 106 patients (8); concurrent medications may have affected results (9).
  • A double-blind RCT of 98 patients with taste disorders found no benefit for zinc gluconate (22.6 mg t.i.d. × 4 months) over placebo, although zinc-deficient participants benefited from treatment (10).
  • In one study, 426 patients with sensorineural olfactory disorder received topical corticosteroids and oral B complex, zinc sulfate (300 mg/day, for "more than 1 month"), or both (11). Zinc benefited only those with posttraumatic olfactory disorder.
• Diarrhea
  • A double-blind RCT of 937 children (age 6 to 35 months) in India found that 20 mg elemental zinc/day as an adjunct to oral rehydration therapy and vitamins reduced the risk of continued diarrhea by 23% [95% confidence interval (CI) 12% to 32%] (12). Another 15-day trial of 684 children (age 6 to 24 months) found that elemental zinc acetate (14.2 mg or 40 mg daily), but not vitamin A [4,500 µg retinol equivalents (RE)], reduced duration of diarrhea 13% and reduced prolonged diarrhea by 43% (13). In 87 hospitalized children (age 6 to 36 months) with persistent diarrhea in Pakistan, 3 mg/kg/day elemental zinc as an adjunct to a rice-lentil and yogurt diet (14) provided no additional benefit in malnourished children with persistent diarrhea. Zinc decreased already low plasma copper levels and may be detrimental in severely malnourished children.
• Head injury
  • A double-blind RCT found a benefit for supplemental zinc versus standard zinc therapy in 68 patients with severe closed-head injury on Glasgow coma scale scores and mortality rates (15). More controls underwent craniotomy, possibly skewing results.
• Atopic eczema
  • A double-blind placebo-controlled trial found no benefit for oral zinc sulphate (185.4 mg/day × 8 weeks) in 50 children with atopic eczema (16).
• Tinnitus
  • A double-blind, placebo-controlled trial found no benefit of oral zinc sulphate (22 mg elemental zinc t.i.d. × 8 weeks) in 48 patients with tinnitus and normal serum zinc levels (17).
  • Macular degeneration
  • A double-blind, placebo-controlled RCT in 112 patients with age-related, bilateral macular degeneration and unilateral exudative lesions found no benefit of zinc sulfate (200 mg q.d. × 2 years) in preventing progression in the second eye (18).
• Leg ulcers
  • A systematic review of six RCTs found no benefit of zinc sulfate for healing chronic venous or arterial ulcers (19).
• Infant/fetal growth
  • A placebo-controlled RCT in apparently healthy breast-fed infants (6 to 12 months) in Ethiopia found that zinc sulfate (10 mg q.d. for 6 days a week × 6 months) increased weight and length in stunted and nonstunted infants and decreased morbidity (20).
  • A double-blind RCT in 580 healthy African-American pregnant women with low zinc levels tested zinc sulfate (25 mg/day from 19 weeks gestational age until delivery). All received a zinc-free multivitamin/mineral. Zinc-supplemented infants, compared with placebo-treated infants, had significantly greater birthweight and head circumference (21).
• Arthritis
  • Three placebo-controlled studies in a total of 86 patients with rheumatoid arthritis (RA) found no benefit of zinc sulphate (up to 220 mg t.i.d.) on clinical criteria (22–24). The longest trial lasted 4 months.
  • A double-blind placebo-controlled crossover trial in 24 participants with psoriatic arthritis (220 mg zinc sulphate t.i.d. × 6 weeks) found that zinc significantly benefited joint pains (but not overall condition, morning stiffness, or functional capacity) (25).

[Outline]

• CClinical Trials
  • Colds
  • Taste and smell
  • Diarrhea
  • Head injury
  • Atopic eczema
  • Tinnitus
  • Leg ulcers
  • Infant/fetal growth
  • Arthritis

[ADP ] Letter Key

Adverse Reactions

• Zinc can cause nausea, vomiting, mouth irritation, dysgeusia, abdominal pain, or diarrhea.
• Excessive zinc interferes with copper absorption (probably by inducing metallothionein, which has a higher affinity for copper than for zinc). A dose of 60 mg zinc daily for several weeks depresses erythrocyte copper-zinc superoxide dismutase. A dose of 50 mg zinc gluconate × 10 weeks reduced hemoglobin and serum ferritin. Elevated zinc concentration reduces high density lipoprotein (HDL)-cholesterol, increases low density lipoprotein (LDL)-cholesterol, and impairs lymphocyte and neutrophil function (1). A 17-year-old who ingested up to 300 mg zinc daily for almost 2 years developed anemia, leukopenia, neutropenia, fatigue, headaches, and reduced serum copper (26). Zinc discontinuation resolved all signs and symptoms in 2 months.
• Exposure to nonsupplemental zinc
  • Zinc compounds (especially zinc chloride in concentrations greater than 20%) can erode the gastrointestinal tract and may cause acute tubular necrosis or interstitial nephritis. Gastrointestinal symptoms are more likely after ingesting zinc compounds than elemental zinc (1). Chronic ingestion of more than 425 pennies (97.6% zinc, 2.4% copper) caused diarrhea and gastrointestinal bleeding; the patient died from bacterial and fungal sepsis (1).
  • Injected zinc sulfate caused hypotension, diarrhea, vomiting, pulmonary edema, jaundice, elevated amylase concentrations, oliguria, anemia, and thrombocytopenia (1).
  • Inhaled zinc chloride can produce chemical pneumonitis and adult respiratory distress syndrome. Zinc oxide fumes can cause metal fume fever, with fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, and metallic taste. Exposed workers can develop tolerance but lose it over a weekend, causing this illness to be termed "Monday morning fever."
  • Topical zinc chloride and zinc acetate are more irritating to the skin than zinc sulfite or zinc oxide.
• Minimum risk concentration = 0.3 mg zinc/kg/day.
• Lowest observed adverse effect concentration (LOAEL) = 1 mg zinc/kg/day.
• Maximum contaminant concentration for U.S. drinking water = 5 mg zinc/L.
• Permissible exposure limit-time weighted average (PEL-TWA) zinc oxide fumes 5 mg/m³, short-term exposure limit (STEL) 10 mg/m³.

Drug Interactions

• Tetracycline: zinc decreases absorption (27)
• Fluoroquinolones: zinc decreases absorption of ciprofloxacin and norfloxacin (28)
• Folic acid (2)
• Iron (2)
• Calcium: may decrease absorption of zinc (2)

Pregnancy/Lactation

• Low zinc concentration in breast milk can cause acrodermatitis, irritability, and delayed growth in breast-fed infants (1).

[Outline]

• AAdverse Reactions
  • Exposure to nonsupplemental zinc
• DDrug Interactions
• PPregnancy/Lactation

[DFL ] Letter Key

Deficiency Signs and Symptoms

• Factors predisposing to zinc deficiency (3): Inadequate dietary intake, celiac disease, pancreatic insufficiency, inflammatory bowel disease, malabsorption, starvation, burns, diabetes, ketoacidosis, diuretic treatment, kidney damage, liver disease, sickle cell anemia, porphyria, chelation therapy, chronic blood loss, parasites, dialysis, exfoliative dermatitis, and excessive sweating.
• Zinc deficiency diseases include hypogonadal dwarf syndrome (growth retardation, anemia, altered taste and smell, poor wound healing, and hepatosplenomegaly), and acrodermatitis enteropathica (an inherited disorder characterized by alopecia, hypertrophic, ulcerated skin, chronic diarrhea, and muscle wasting) (1).
• Symptoms of deficiency (3): Anorexia, impaired smell and taste, growth retardation, hypogonadism, delayed wound healing, impotence (in renal dialysis patients), depression, intention tremor, nystagmus, dysarthria, jitteriness, photophobia, skin lesions, paronychia, nail abnormalities (growth arrest, loss, Beau’s lines), hair growth arrest, diarrhea, decreased cell-mediated immune function, and decreased folic acid availability (because dietary folate is hydrolyzed by the zinc-dependent enzyme pteroylpolyglutamate hydrolase).

Factors Decreasing Availability/Absorption

• Phytate, fiber, iron (especially ferrous), high calcium intake (especially with a phytate-rich diet), folic acid (may impair zinc status if zinc levels are low; studies are mixed) (2).

Laboratory Tests

• Plasma zinc: 70 to 130 µg/dL.
• Levels less than 50 µg/dL or hair concentration less than 70 µg/g may indicate deficiency (3).

[Outline]

• DDeficiency Signs and Symptoms
• FFactors Decreasing Availability/Absorption
• LLaboratory Tests

[RU ] Letter Key

Recommended Dietary Allowance

Upper Limits

• Quality note: Zinc gluconate tablets contain 14.3% zinc by weight. Zinc sulfate contains 23% zinc by weight (1).
• Zinc gluconate lozenges: One lozenge (>= 13.3 mg elemental zinc) every 2 hours while awake. Flavoring compounds, including citric acid and tartaric acid and possibly mannitol and sorbitol, may chelate zinc, diminishing efficacy.

[Outline]

• RRecommended Dietary Allowance
• UUpper Limits

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