Highlights & Basics
- Zinc deficiency is rarely severe and usually congenital. Milder zinc deficiency is usually acquired and is common in older people.
- Manifestations of zinc deficiency may be subtle and can affect many organ systems. Delayed wound healing, impaired taste, loss of appetite, hair loss, fertility issues, and increased susceptibility to infection are common manifestations.
- Plasma or serum zinc levels are useful in the evaluation of patients with suspected zinc deficiency. Milder forms of zinc deficiency may not be detected in plasma or serum tests, but supplementation may still be considered for patients with typical symptoms.
- In most cases, standard oral zinc supplementation leads to increased zinc levels and amelioration of symptoms.
- Zinc supplementation is generally safe, although acute toxicity with high doses may lead to adverse changes in immune, iron, copper, and cholesterol status, as well as to potential genitourinary problems.
Quick Reference
History & Exam
Key Factors
increased susceptibility to infection
taste disorders
stomatitis
delayed wound healing
acrodermatitis enteropathica
fertility issues/adverse pregnancy outcomes
Other Factors
fatigue
gastrointestinal symptoms
short stature
bone fracture
impaired glucose tolerance
dermatitis
weight loss
alopecia
paronychia
fever
intention tremor
depression
impaired concentration
nystagmus
dysarthria
night blindness
hypogeusia
anosmia
blepharitis
dementia
Diagnostics Tests
1st Tests to Order
serum or plasma zinc levels
serum iron level
serum 25-OH vitamin D level
serum folate
serum vitamin B12
Emerging Tests
cell zinc content
analysis of zinc levels in hair
genetic testing for acrodermatitis enteropathica
Treatment Options
acute
acquired
zinc supplementation
treatment of underlying condition and symptomatic care
copper supplementation
acrodermatitis enteropathica
lifelong zinc supplementation
copper supplementation
Definition
Classifications
Acrodermatitis enteropathica
Acquired zinc deficiency
Vignette
Common Vignette 1
Common Vignette 2
Other Presentations
Epidemiology
Etiology
- Nutritional: diet low in meat, high in phytates (found in whole grains and soy products) or oxalates (found in many vegetables including spinach, nuts, okra, and tea)
- Host: presence of a chronic disease (chronic gastrointestinal [GI] disease, liver disease, diabetes mellitus, sickle cell disease, renal disease, alcoholism, HIV infection) or chronic or recurrent infections.
Pathophysiology
Images
Diagnostic Approach
Clinical evaluation
- Alcoholics tend to be deficient in zinc, along with a variety of other nutrients
- Low meat intake or high phytate/oxalate intake can contribute to zinc deficiency. Phytates and oxalates are found in many grain and vegetable products including soy, bran, whole grains, spinach, berries, chocolate, and tea. This is compounded by the tendency of diets low in meat to be high in the fibrous plant products that bind zinc, further limiting absorption.
- Growth and development: growth retardation, hypogonadism, osteopenia (increased risk of bone fracture), weight loss
- Neurologic: intention tremor, depression, impaired concentration, nystagmus, dysarthria, night blindness, hypogeusia, anosmia, dementia
- Dermatologic: alopecia, dermatitis, paronychia, stomatitis
- Gastrointestinal: anorexia, abdominal pain, diarrhea, glossitis
- Miscellaneous: fatigue, delayed wound healing, fever, pica, increased infections, blepharitis, impaired glucose tolerance, infertility/adverse pregnancy outcomes, taste disorders.
Laboratory tests
- Cell zinc content: because 95% of zinc is intracellular, zinc levels in a variety of cell populations (red blood cells, platelets, white blood cells) have been evaluated in research settings. Although cellular zinc levels fluctuate less than serum, they are technically more difficult than serum- or plasma-based tests, and superiority has not been clearly demonstrated.[73]
- Analysis of zinc levels in hair: the utility of hair zinc analysis is unclear, and has been used primarily in research settings.[73]
Risk Factors
History & Exam
Tests
Differential Diagnosis
Hypothyroidism
Differentiating Signs/Symptoms
- May be clinically difficult to differentiate.
- Headaches, cold intolerance, hearing impairment, muscle cramps, modest weight gain, dry skin, eyelid edema, thick tongue, facial edema.
Differentiating Tests
- Serum thyroid-stimulating hormone (TSH): elevated TSH level.
Depression
Differentiating Signs/Symptoms
- May be clinically difficult to differentiate.
- History of depressed mood, anhedonia, libido changes, sleep disturbance, psychomotor problems, excessive guilt, poor concentration, suicidal ideation.
Differentiating Tests
- Clinical diagnosis.
- Serum or plasma zinc levels: normal.
Iron deficiency
Differentiating Signs/Symptoms
- May coexist with cases of zinc deficiency and be difficult to differentiate clinically.
Differentiating Tests
- CBC with peripheral smear: microcytic anemia; pale red cells with anisopoikilocytosis (variation in size and shape) and pencil cells.
- Serum iron: low.
- TIBC (total iron binding capacity): increased.
- Transferrin saturation: <16%.
- Serum ferritin: low.
Vitamin B12 deficiency
Differentiating Signs/Symptoms
- May coexist with cases of zinc deficiency and be difficult to differentiate clinically.
Differentiating Tests
- CBC with peripheral smear: macrocytic anemia; leukopenia or thrombocytopenia (severe disease); hypersegmented polymorphonucleated cells and megalocytes. May have normal hematologic parameters in mild disease.
- Serum vitamin B12 level: <200 picograms/mL.
Folate deficiency
Differentiating Signs/Symptoms
- May coexist with cases of zinc deficiency and be difficult to differentiate clinically.
Differentiating Tests
- CBC with peripheral smear: macrocytic anemia; leukopenia or thrombocytopenia (severe disease); hypersegmented polymorphonucleated cells and megalocytes. May have normal hematologic parameters in mild disease.
- Serum folate level: <3 nanograms/mL (<7 nmol/L).
Vitamin D deficiency
Differentiating Signs/Symptoms
- May coexist with cases of zinc deficiency and be difficult to differentiate clinically.
Differentiating Tests
- Serum 25 dihydroxyvitamin D level: low (<15 nanograms/mL).
Differentiating Signs/Symptoms
- May coexist with cases of zinc deficiency and be difficult to differentiate clinically.
Differentiating Tests
- Serum vitamin A level: low.
Screening
Treatment Approach
Zinc supplementation
- 3 mg/day for children <4 years
- 5 mg/day for children 4 to 8 years
- 8 mg/day for children 9 to 13 years
- 9 mg/day for nonpregnant and nonlactating adult women
- 11 mg/day for adult men
- 11 to 12 mg/day in pregnancy and lactation.
Treatment Options
acquired
zinc supplementation
Primary Options
Secondary Options
- zinc sulfate
2.5 to 5 mg intravenously once daily
- zinc sulfate
Comments
- For most people with acquired zinc deficiency, zinc can be adequately replenished with oral supplementation, with few adverse effects and at low cost. Unless the underlying cause can be adequately addressed (e.g., celiac disease or dietary insufficiency), lifelong supplementation should be considered.
- Formulations of supplements include zinc sulfate, zinc acetate, zinc gluconate, zinc aspartate, and zinc orotate. It is important to note that the bioavailability of zinc formulations may differ significantly (e.g., zinc oxide is less well absorbed than zinc aspartate or zinc orotate).
- People with zinc deficiency should be monitored every 1 to 3 months to ensure that manifestations resolve and serum zinc levels normalize with supplementation. Once zinc status has normalized, patients with ongoing risk factors should be monitored every 12 months, or sooner if symptoms recur.
- Copper levels should also be monitored in patients on long-term, high-dose zinc supplementation, and copper supplementation given if necessary.
- Parenteral zinc is rarely necessary, except for patients with intestinal failure and/or on prolonged total parenteral nutrition.[90]
treatment of underlying condition and symptomatic care
Comments
- For most people with acquired zinc deficiency, focus on amelioration of the predisposing condition is appropriate.
- Conditions that place patients at risk for zinc deficiency include: malabsorption syndrome, chronic gastrointestinal (GI) (celiac disease or Crohn disease) and liver disease, renal disease, diabetes mellitus, sickle cell disease, and HIV infection.[14] [15] [16] [17] [18] [19] [20] [91] [8] [21] [22] [23] [24] [25] Also those undergoing chronic treatment with certain medication (e.g., hydrochlorothiazide, penicillamine, ethambutol, certain antibiotics), alcoholics, vegetarians, vegans, and infants with nutrient-poor diets are more prone to zinc deficiency.[26] [27] [28] Zinc deficiency in older people contributes to susceptibility to infection and osteoporosis.[29] [30] Zinc supplementation has been shown to reduce the risk of infection in one study.[33]
- Symptomatic management to alleviate GI symptoms (anorexia, glossitis, abdominal pain, diarrhea) may be required.
copper supplementation
Primary Options
copper
3 mg orally once daily
Comments
- Patients on long-term, high-dose zinc supplementation should be monitored for resulting copper deficiency. If copper deficiency is detected, low-dose copper supplementation is typically effective.
acrodermatitis enteropathica
lifelong zinc supplementation
Primary Options
Comments
- In acrodermatitis enteropathica, supplementation doses are taken for life. Long-term zinc supplementation may be guided by serial serum zinc measurement to individualize dose. Copper levels should also be monitored and supplementation given if necessary.
- Cessation of therapy leads to recurrence of signs and symptoms.
- Because the skin manifestations of zinc deficiency are linked to enzyme impairment, topical treatments are generally ineffective.
copper supplementation
Primary Options
copper
3 mg orally once daily
Comments
- Zinc competes with copper absorption, so copper levels should be assessed regularly, and concurrent copper supplementation may be occasionally necessary.
Prevention
Primary Prevention
Follow-Up Overview
Prognosis
Monitoring
Complications
Citations
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Haase H, Overbeck S, Rink L. Zinc supplementation for the treatment or prevention of disease: current status and future perspectives. Exp Gerontol. 2008 May;43(5):394-408. [Abstract]
Haider BA, Bhutta ZA. The effect of therapeutic zinc supplementation among young children with selected infections: a review of the evidence. Food Nutr Bull. 2009 Mar;30(1 suppl):S41-59.[Abstract][Full Text]
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Key Articles
Other Online Resources
Referenced Articles
Guidelines
Diagnostic
Summary
Zinc deficiency is characterized by growth retardation, loss of appetite, and impaired immune function. In more severe cases it may cause hair loss, diarrhea, delayed sexual maturation, impotence, and, in males, hypogonadism.Published by
Centers for Disease Control and Prevention
Published
2019
Summary
Sets forth criteria for: diagnosing zinc deficiency with one or more symptoms of zinc deficiency or low serum alkaline phosphatase, ruling out other diseases, and low serum zinc.Published by
The Japanese Society of Clinical Nutrition
Published
2020
Treatment
Summary
Dietary recommendations by life stage, from birth through older adulthood.Published by
US Department of Health and Human Services; US Department of Agriculture
Published
2020