Zinc Deficiency

para>5 " 35% of ambulatory elderly may have zinc-deficient diets (1,5).

Zinc deficiency may cause chronic ulcers and impaired recovery from infections. Poor night vision may contribute to increased falls/accidents. Loss of taste, which may contribute to worsening nutrition (6)

Reactive oxygen species leading to inflammation are involved in many chronic diseases attributed to aging: atherosclerosis and coronary artery disease, Alzheimer disease, neurodegenerative disorders, diabetes mellitus type 2, and cancer (1,3).

Increased depression and poor cognitive function in the elderly are associated with low zinc levels.

Decreased immune function: Zinc supplementation in one study, elderly subjects decreased the incidence of infection (1)[B].

Pediatric Considerations

Zinc deficiency may cause failure to thrive and may impair growth and development of secondary sexual characteristics (3).
Peak requirements during pubertal growth spurt (ages 10 to 15 years old) (2)
Supplementing deficient children decreases mortality from diarrhea (7)[A] and pneumonia in certain populations (7)[B].

Pregnancy Considerations

Requirements increase; deficiency may cause spontaneous abortion, preterm labor. Supplementation in deficient individuals reduces preterm labor but does not improve birth weight (8)[A].
Severe deficiency is associated with congenital malformations and increased maternal morbidity.

EPIDEMIOLOGY

Prevalence

Rare in the United States
Globally: Estimated 16% (1.1 billion people) are at risk for deficiency, 90% at risk live in Africa and Asia.
Highly correlated to per capita gross national income (9)
May be as high as 28% in hospitalized elderly patients
Estimated 5 " 35% in ambulatory elderly
Predominant age: all ages
Predominant sex: male = female

ETIOLOGY AND PATHOPHYSIOLOGY

Insufficient dietary intake
- Diet lacking in animal proteins (dairy, eggs, meat, seafood)
- Parenteral hyperalimentation without zinc supplementation
- Breastfeeding (infants)
- Alcoholism
- Cystic fibrosis
Increased requirements
- Pregnancy
- Lactation
- Rapid growth phase in childhood
- Burns
- Major trauma
- Systemic illness resulting in oxidative stress
Increased losses
- Diabetes
- Cirrhosis
- Renal disease
- Dialysis
- Inflammatory bowel disease, steatorrhea, enterostomy, fistula
- Sickle cell disease
- Diuretics: thiazides, chlorthalidone
Decreased absorption
- Diet high in phytates (plant fiber)
- Acrodermatitis enteropathica, an autosomal recessive deficiency in the enzyme required for intestinal absorption. These patients have bullous pustular dermatitis around oral, anal, genital orifices, thymic dysplasia, diarrhea, malabsorption, steatorrhea, and multiple repeat infections. It is fatal if untreated, although complete recovery possible with adequate supplementation.
- Parasitism
- Drugs: chelating agents, penicillamine, tetracyclines, quinolones, bisphosphonates

Genetics

Usually acquired
Rarely caused by acrodermatitis enteropathica (autosomal recessive inheritance)
Associated with sickle cell anemia (autosomal recessive)

RISK FACTORS

Drugs: diuretics, penicillamine, sodium valproate, iron chelators, ACEI/ARB, cisplatin
Low socioeconomic status
Living in developing nations
Strict vegetarian diet
Malabsorption syndromes
Thermal burns
Alcoholism
Chronic renal failure

GENERAL PREVENTION

Adequate diet
Supplementation when indicated (see "Medication " )

COMMONLY ASSOCIATED CONDITIONS

Acrodermatitis enteropathica
Sickle cell anemia
Malabsorption
Advanced age
Diarrheal illness

DIAGNOSIS

HISTORY

Mild deficiency
- Hypogeusia (decreased taste)
- Dysosmia (altered smell sensation)
- Decreased adaptation to dark
- Oligospermia
- Decreased serum testosterone level
- Decreased lean body mass
- Hyperammonemia
- Decreased IL-2 activity of T helper cells
Moderate deficiency
- All of the above
- Diarrhea
- Growth retardation
- Hypogonadism (especially male)
- Mental lethargy
- Rough skin
- Delayed wound healing
- Glucose intolerance
- Impaired cell-mediated immunity
- Hair brittle and easily broken
Severe deficiency
- All of the above
- Bullous pustular dermatitis
- Weight loss
- Growth restriction
- Recurrent infections
- Neurosensory disorders
- Nonhealing ulcers
- Emotional instability
- Tremors
- Ataxia
- Alopecia
- Death

PHYSICAL EXAM

Depends on level of deficiency
Acrodermatitis enteropathica: Erythema, scales, erosions, and/or vesiculobullous eruptions often quite dramatic in diaper area.

DIFFERENTIAL DIAGNOSIS

Congenital dwarfism
Failure to thrive in infants
Multiple micronutrient deficiencies
Primary hypogonadism
Intellectual disability

DIAGNOSTIC TESTS & INTERPRETATION

Diagnosis depends on clinical suspicion.
Plasma zinc levels are insensitive markers of deficiency, and decreased levels occur late when body wide zinc pool is depleted. Diurnal variation (highest level at 10 am), inflammation, pregnancy, oral contraceptive use, fasting/eating all affect status. Represents 0.1% of total body zinc. 70% zinc bound to albumin.
Plasma zinc concentrations are decreased in the presence of acute phase reactants (CRP) (5).
<60 ¼g/dL suggestive of deficiency, <50 ¼g/dL correlates with clinical signs
Urine zinc excretion: not enough data to use this in screening, although if deficient will have hypozincuria
Granulocyte or lymphocyte levels, alkaline phosphatase in granulocytes are other measures that are infrequently used (1).

TREATMENT

GENERAL MEASURES

Dietary diversification: increased animal proteins in diet, decreased phytates

MEDICATION

Zinc supplements (take at least 1 hour before or 2 hours after meals high in calcium and phytates. Take 4 hours before or 2 hours after fluoroquinolone or tetracycline class drugs and penicillamine.
Various salt forms available; dose by elemental zinc content.
Oral form: zinc gluconate (lozenges, tablets), zinc sulfate (capsules, tablets, extended-release tablets)
Injectable form: zinc chloride, zinc sulfate
Use the recommended dietary allowance (RDA) as a guideline for dosing (see "Diet " ).
Malnourished children: supplementation: 5 mg/day 7 months to 3 years, 10 mg/day >3 years.
Malnourished children: Prophylaxis in acute onset diarrhea: >6 months with mild deficiency 10 mg/day, moderate/severe 20 mg/day for 10 to 14 days. <6 months 10 mg/day for 10 to 14 days (2).
In adult patient, 2.5 to 5 mg/day of elemental zinc is recommended in parenteral nutrition; may add additional doses (20 mg IV over 10 hours) if suspect deficiency or ongoing zinc losses (increase stoma or stool output, burns, diarrhea, major trauma or sepsis), though optimal dose is unknown. Although relatively more zinc is needed for healing involved in critical illness, routine high-dose supplementation in critically ill does not improve mortality or result in decreased length of stay (10)[A].
Tolerable upper level for adults for zinc is 40 mg/day (5).

ADDITIONAL THERAPIES

Common cold: Zinc lozenges (zinc acetate or zinc gluconate) may decrease symptom duration if started within 24 hours of symptom onset. Two to four times daily for 14 days
Wilson disease: used to decrease copper levels by decreasing copper uptake and inducing metallothionein T
Age-related macular degeneration: prevents advancement of disease

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Full activity
Patient Monitoring

In patients receiving parenteral nutrition, obtain zinc at baseline and every 2 to 4 weeks. If dose is changed, measure 1 to 2 weeks until stable level is achieved.
Clinical status such as improved energy, weight gain, resolution of symptoms

DIET

Balanced omnivorous diet or vegetarian diet with supplementation
Avoid excessive intake of foods with high-phytate content (e.g., raw cereals).
Lean beef and pork, oysters, poultry, seafood, milk, eggs, beans, fortified cereals are rich in zinc.
RDA for elemental zinc (4)[C]:
- Men: 11 mg/day
- Women: 8 mg/day
- Pregnant women >19 years old: 11 mg/day
- Breastfeeding women: 12 mg/day
- Children 7 months to 3 years: 3 mg; 4 to 8 years: 5 mg; 9 to 13 years: 8 mg; 14- to 18-year-old males: 11 mg; females 14 to 18 years: 9 mg; pregnant: 12 mg, lactation 13 mg

PROGNOSIS

Immediate improvement in clinical status with treatment; full resolution of signs and symptoms
Early intervention in deficient children can improve growth trajectory.

REFERENCES

11 Prasad AS. Discovery of human zinc deficiency: its impact on human health and disease. Adv Nutr. 2013;4(2):176 " 190.22 Roohani N, Hurrell R, Kelishadi R, et al. Zinc and its importance for human health: an integrative review. J Res Med Sci. 2013;8(2):144 " 157.33 Cabrera J. Zinc, aging, and immunosenescence: an overview. Pathobiol Aging Age Relat Dis. 2015;5:25592.44 National Institutes of Health. Zinc. http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/. Accessed July 6, 2015.55 Livingstone C. Zinc: physiology, deficiency, and parenteral nutrition. Nutr Clin Pract. 2015;30(3):371 " 382.66 Mocchegiani E, Romeo J, Malavolta M, et al. Zinc: dietary intake and impact of supplementation on immune function in elderly. Age (Dordr). 2013;35(3):839 " 860.77 Liberato SC, Singh G, Mulholland K. Zinc supplementation in young children: a review of the literature focusing on diarrhoea prevention and treatment. Clin Nutr. 2015;34(2):181 " 188.88 Ota E, Mori R, Middleton P, et al. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev. 2015;(2):CD000230.99 Kumssa DB, Joy EJ, Ander EL, et al. Dietary calcium and zinc deficiency risks are decreasing but remain prevalent. Sci Rep. 2015;5:10974. doi: 10.1038/srep10974.1010 Heyland DK, Jones N, Cvijanovich NZ, et al. Zinc supplementation in critically ill patients: a key pharmaconutrient? JPEN J Parenter Enteral Nutr. 2008;32(5):509 " 519.

ADDITIONAL READING

Wessells KR, King JC, Brown KH. Development of a plasma zinc concentration cutoff to identify individuals with severe zinc deficiency based on results from adults undergoing experimental severe dietary zinc restriction and individuals with acrodermatitis enteropathica. J Nutr. 2014;144(8):1204 " 1210.
Wieringa FT, Dijkhuizen MA, Fiorentino M, et al. Determination of zinc status in humans: which indicator should we use? Nutrients. 2015;7(5):3252 " 3263.

CODES

ICD10

E60 Dietary zinc deficiency
E83.2 Disorders of zinc metabolism

ICD9

269.3 Mineral deficiency, not elsewhere classified

SNOMED

zinc deficiency (disorder)
Dietary zinc deficiency (disorder)
Secondary acquired zinc deficiency (disorder)

CLINICAL PEARLS

Zinc deficiency is uncommon in the United States.
Elderly persons living in long-term facilities may have diets deficient in zinc.
Zinc deficiency may cause poor wound healing; consider supplementation when treating chronic skin ulcers.

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