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YOU ARE HERE
Minerals » Zinc
ZINC
Contents
* Summary
* Function
* Catalytic role
* Structural role
* Regulatory role
* Nutrient interactions
* Deficiency
* Inherited deficiency
* Acquired deficiency
* Individuals at risk
* Biomarkers of zinc status
* The RDA
* Disease Prevention
* Pregnancy complications and
adverse pregnancy outcomes
* Impaired growth and development
* Impaired immune system function
* Type 2 diabetes mellitus
* Disease Treatment
* Wilson's disease
* Common cold
* Age-related macular degeneration
* Diabetes mellitus
* HIV/AIDS
* Alzheimer's disease
* Depression
* Neonatal sepsis
* Sources
* Food
* Supplements
* Safety
* Toxicity
* Drug interactions
* LPI Recommendation
* Authors and Reviewers
* References
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SUMMARY
* Zinc is a nutritionally essential mineral needed for catalytic, structural,
and regulatory functions in the body. (More information)
* Severe zinc deficiency is rare and caused by an inherited condition called
acrodermatitis enteropathica. Acquired zinc deficiency is primarily due to
malabsorption syndromes and chronic alcoholism. (More information)
* Dietary zinc deficiency is quite common in the developing world, affecting an
estimated 2 billion people. Consumption of diets high in phytate and lacking
foods from animal origin drive zinc deficiency in these populations. (More
information)
* The recommended dietary allowance (RDA) for adult men and women is 11 mg/day
and 8 mg/day of zinc, respectively. (More information)
* Long-term consumption of zinc in excess of the tolerable upper intake level
(UL; 40 mg/day for adults) can result in copper deficiency. (More
information)
* Dietary zinc deficiency has been associated with impaired growth and
development in children, pregnancy complications, and immune dysfunction with
increased susceptibility to infections. (More information)
* Supplementation with doses of zinc in excess of the UL is effective to reduce
the duration of common cold symptoms. The use of zinc at daily doses of 50 to
180 mg for one to two weeks has not resulted in serious side effects. (More
information)
* Current evidence suggests that supplemental zinc may be useful in the
management of chronic conditions, such as age-related macular degeneration,
diabetes mellitus, Wilson’s disease, and HIV/AIDS. (More information)
* Zinc bioavailability is relatively high in meat, eggs, and seafood; zinc is
less bioavailable from whole grains and legumes due to their high content in
phytate that inhibits zinc absorption. (More information)
Zinc is an essential trace element for all forms of life. Clinical zinc
deficiency in humans was first described in 1961, when the consumption of diets
with low zinc bioavailability due to high phytate content (see Food sources) was
associated with "adolescent nutritional dwarfism" in the Middle East (1). Since
then, zinc insufficiency has been recognized by a number of experts as an
important public health issue, especially in low-resource countries (2, 3).
FUNCTION
Numerous aspects of cellular metabolism are zinc-dependent. Zinc plays important
roles in growth and development, immune function, neurotransmission, vision,
reproduction, and intestinal ion transport (4). Using data mining approaches, it
has been estimated that over 3,000 proteins in humans have functional
zinc-binding sites (5). At the cellular level, the function of zinc can be
divided into three categories: (1) catalytic, (2) structural, and (3) regulatory
(6).
CATALYTIC ROLE
Over 50 different enzymes depend on zinc for their ability to catalyze vital
chemical reactions (7). Zinc-dependent enzymes can be found in all six classes
of enzymes (8), as defined by the International Union of Biochemistry and
Molecular Biology (9). During enzymatic reactions, zinc may have either a direct
catalytic role or a structural role (i.e., stabilizing the structure of
catalytic enzymes; see below).
STRUCTURAL ROLE
Zinc plays an essential role in the folding of some proteins. A finger-like
structure, known as a zinc finger motif, stabilizes the structure several
proteins. Examples of zinc finger proteins include the superfamily of nuclear
receptors that bind and respond to steroids and other molecules, such as
estrogens, thyroid hormones, vitamin D, and vitamin A (10). Zinc finger motifs
in the structure of nuclear receptors allow them to bind to DNA and act as
transcription factors to regulate gene expression (see Regulatory role). Zinc
finger motifs are also involved in interactions of proteins with other proteins,
ribonucleotides, and lipids (6). Removal of zinc from zinc-containing proteins
results in protein misfolding and loss of function.
Metallothioneins are examples of proteins with a zinc-binding motif.
Metallothioneins are small metal-binding cysteine-rich proteins with a high
affinity for zinc. They work in concert with zinc transporters, regulating free
zinc concentrations in the cytosol (11). Metallothioneins are also involved in
the regulation of metal ion homeostasis, cellular defense against oxidative
stress, and detoxification of heavy metals (11, 12).
The antioxidant enzyme, copper-zinc superoxide dismutase 1 (SOD 1), is made of
two identical dimers, each including an active site with a catalytic copper ion
and a structural zinc ion. Demetalation of SOD1 has been implicated in the
formation of amyloid aggregates in some forms of inherited amyotrophic lateral
sclerosis (ALS) — a motor neuron disease leading to muscle atrophy and paralysis
(13).
REGULATORY ROLE
Zinc finger proteins have been found to regulate gene expression by acting as
transcription factors (see above). Zinc also plays a role in cell signaling via
the metal-response element (MRE)-binding transcription factor 1 (MTF1); MTF1 has
a zinc finger domain that allows its binding to MRE sequences in the promoter of
target genes and the subsequent expression of zinc-responsive genes (6). Zinc
may also have a direct regulatory function, modulating the activity of
cell-signaling enzymes and transcription factors (6). Extracellular zinc can
also stimulate a zinc-sensing receptor that triggers the release of
intracellular calcium, a second messenger in signaling pathways (14). Zinc has
been found to influence hormone release (see Type 2 diabetes mellitus) (15) and
nerve impulse transmission (16).
NUTRIENT INTERACTIONS
COPPER
Taking large quantities of zinc (50 mg/day or more) over a period of weeks can
interfere with copper bioavailability. High intake of zinc induces the
intestinal synthesis of a copper-binding protein called metallothionein (see the
article on Copper). Metallothionein traps copper within intestinal cells and
prevents its systemic absorption (see Wilson’s disease). More typical intakes of
zinc do not affect copper absorption, and high copper intakes do not affect zinc
absorption (17).
IRON
Iron and zinc compete for absorptive pathways (18). Supplemental (38-65 mg/day
of elemental iron) but not dietary levels of iron may decrease zinc absorption
(18, 19). This interaction is of concern in the management of iron
supplementation during pregnancy and lactation and has led some experts to
recommend zinc supplementation for pregnant and lactating women taking iron
supplements (20, 21). Food fortification with iron has not been shown to
negatively affect zinc absorption (22). In a placebo-controlled study,
supplementation with zinc (10 mg/day) for three months in children aged eight to
nine years significantly decreased serum iron concentrations, yet not to the
extent of causing anemia (23). Additional randomized controlled studies have
reported a worsening of nutritional iron status with chronic zinc
supplementation (24, 25).
CALCIUM
High levels of dietary calcium impair zinc absorption in animals, but it is
uncertain whether this occur in humans (17). One study showed that increasing
the calcium intake of postmenopausal women by 890 mg/day in the form of milk or
calcium phosphate (total calcium intake, 1,360 mg/day) reduced zinc absorption
and zinc balance in postmenopausal women (26). However, another study found that
increasing the calcium intake of adolescent girls by 1,000 mg/day in the form of
calcium citrate malate (total calcium intake, 1,667 mg/day) did not affect zinc
absorption or balance (27). Calcium in combination with phytate might affect
zinc absorption, which would be particularly relevant to individuals who very
frequently consume tortillas made with lime (i.e., calcium oxide). A study in 10
healthy women (age range, 21-47 years) found that high intake of dietary calcium
(~1,800 mg/day) did not impair zinc absorption regardless of the phytate content
of the diet (28). For more information on phytate, see Food sources.
FOLATE
The bioavailability of dietary folate (vitamin B9) is increased by the action of
a zinc-dependent enzyme. Accordingly, some studies found low zinc intake
decreased folate absorption. It was also suggested that supplementation with
folic acid — the synthetic form of folate — might impair zinc utilization in
individuals with marginal zinc status (17, 29). However, one study reported that
supplementation with a relatively high dose of folic acid (800 µg/day) for 25
days did not alter zinc absorption or status in a group of students being fed a
low-zinc diet (3.5 mg/day) (30).
VITAMIN A
Zinc and vitamin A interact in several ways. Zinc is a component of
retinol-binding protein, a protein necessary for transporting vitamin A in the
blood. Zinc is also required for the enzyme that converts retinol (vitamin A) to
retinal. This latter form of vitamin A is necessary for the synthesis of
rhodopsin, a protein in the eye that absorbs light and thus is involved in dark
adaptation. Zinc deficiency has been associated with a decreased release of
vitamin A from the liver, which may contribute to symptoms of night blindness
that are seen with zinc deficiency (31, 32).
DEFICIENCY
INHERITED ZINC DEFICIENCY
Much of what is known about severe zinc deficiency was derived from the study of
individuals born with acrodermatitis enteropathica, a genetic disorder resulting
from the impaired uptake and transport of zinc (33). The symptoms of severe zinc
deficiency include the slowing or cessation of growth and development, delayed
sexual maturation, characteristic skin rashes, chronic and severe diarrhea,
immune system deficiencies, impaired wound healing, diminished appetite,
impaired taste sensation, night blindness, swelling and clouding of the cornea,
and behavioral disturbances. Before the cause of acrodermatitis enteropathica
was known, patients typically died in infancy. Oral zinc therapy results in the
complete remission of symptoms, though it must be maintained indefinitely in
individuals with the genetic disorder (33, 34).
ACQUIRED ZINC DEFICIENCY
It is now recognized that milder zinc deficiency contributes to a number of
health problems, especially common in children who live in low-resource
countries. An estimated 2 billion people worldwide are affected by dietary zinc
deficiency (3). The lack of a sensitive and specific indicator of marginal zinc
deficiency hinders the scientific study of its health implications (8). However,
controlled trials of moderate zinc supplementation have demonstrated that
marginal zinc deficiency contributes to impaired physical and neuropsychological
development and increased susceptibility to life-threatening infections in young
children (34). In fact, zinc deficiency has been estimated to cause more than
450,000 deaths annually in children under five years of age, comprising 4.4% of
global childhood deaths (35). For a more detailed discussion of the relationship
of zinc deficiency to health problems, see the section on Disease Prevention.
In industrialized countries, dietary zinc deficiency is unlikely to cause severe
zinc deficiency in individuals without a genetic disorder, zinc malabsorption or
conditions of increased zinc loss, such as severe burns or prolonged diarrhea.
Severe zinc deficiency has also been reported in individuals undergoing total
parenteral nutrition without zinc, in those who abuse alcohol, and in those who
are taking certain medications like penicillamine (see Drug interactions) (36).
INDIVIDUALS AT RISK OF ZINC DEFICIENCY (6, 36-38):
* Premature and low-birth-weight infants
* Older breast-fed infants and toddlers with inadequate intake of zinc-rich
complementary foods
* Children and adolescents
* Pregnant and lactating (breast-feeding) women, especially adolescents
* Patients receiving total parenteral nutrition (intravenous feedings)
* Malnourished individuals, including those with protein-energy malnutrition
and anorexia nervosa
* Individuals with severe or persistent diarrhea
* Individuals with malabsorption syndromes, including celiac disease and short
bowel syndrome
* Individuals with inflammatory bowel disease, including Crohn's disease and
ulcerative colitis
* Alcoholics and those with alcoholic liver disease who have increased urinary
zinc excretion and low liver zinc levels
* Individuals with chronic renal disease
* Individuals with sickle cell anemia
* Individuals who use medications that decrease intestinal zinc absorption,
increase zinc excretion, or impair zinc utilization (see Drug interactions)
* Older adults (65 years and older)
* Vegetarians: The requirement for dietary zinc may be as much as 50% greater
for vegetarians whose major food staples are grains and legumes, because high
levels of phytate in these foods reduce zinc absorption (see Food sources)
(29).
BIOMARKERS OF ZINC STATUS
Currently, there is not a sensitive and specific biomarker to detect zinc
deficiency in humans. Low plasma or serum zinc concentrations are typically used
as indicators of zinc status in populations and in intervention studies, but
they have a number of limitations, including lack of sensitivity to detect
marginal zinc deficiency, diurnal variations, and confounding by inflammation,
stress, and hormones (38, 39).
THE RECOMMENDED DIETARY ALLOWANCE (RDA)
The recommended dietary allowance (RDA) for zinc is listed by gender and age
group in Table 1. Infants, children, adolescents, and pregnant and lactating
women are at increased risk of zinc deficiency. Since a sensitive indicator of
zinc nutritional status is not readily available, the RDA for zinc is based on a
number of different indicators of zinc nutritional status and represents the
daily intake likely to prevent deficiency in nearly all individuals in a
specific age and gender group (29).
Table 1. The Recommended Dietary Allowance (RDA) for Zinc Life Stage Age Males
(mg/day) Females (mg/day) Infants 0-6 months 2 (AI) 2 (AI) Infants 7-12 months 3
3 Children 1-3 years 3 3 Children 4-8 years 5 5 Children 9-13 years 8 8
Adolescents 14-18 years 11 9 Adults 19 years and older 11 8 Pregnancy 18 years
and younger - 12 Pregnancy 19 years and older - 11 Breast-feeding 18 years and
younger - 13 Breast-feeding 19 years and older - 12
PREVENTION OF DISEASES OR CONDITIONS RELATED TO ZINC DEFICIENCY
PREGNANCY COMPLICATIONS AND ADVERSE PREGNANCY OUTCOMES
Estimates based on national food supply indicate that dietary zinc intake is
likely inadequate in most low- and middle-income countries, especially those in
Sub-Saharan Africa and South Asia (40). Inadequate zinc status during pregnancy
interferes with fetal development, and preterm neonates from zinc-deficient
mothers suffer from growth retardation and dermatitis and are at risk of
infections, necrotizing enterocolitis, chronic lung disease, and retinopathy of
prematurity (4). Maternal zinc deficiency has also been associated with a number
of pregnancy complications and poor outcomes. A recent case-control study
conducted in an Iranian hospital reported higher odds of congenital
malformations in newborns of mothers with low serum zinc concentrations during
the last month of pregnancy (41). A 2016 review of 64 observational studies
found an inverse relationship between maternal zinc status and the severity of
preeclampsia, as well as between maternal zinc intake and the risk of
low-birth-weight newborns (42). There were no apparent associations between
maternal zinc status and the risk of gestational diabetes mellitus and preterm
birth. However, the conclusions of this analysis were limited by the fact that
most observational studies were conducted in women from populations not at risk
for zinc deficiency (42).
To date, available evidence from maternal zinc intervention trials conducted
worldwide does not support the recommendation of routine zinc supplementation
during pregnancy. A 2015 systematic review and meta-analysis of 21 randomized
controlled trials in over 17,000 women and their babies found a 14% reduction in
premature deliveries with zinc supplementation during pregnancy, mainly in
low-income women (43). This analysis, however, did not find zinc supplementation
to benefit other indicators of maternal or infant health, including stillbirth
or neonatal death, low birth weight, small-for-gestational age, and
pregnancy-induced hypertension. There was also no effect of supplemental zinc on
postpartum hemorrhage, maternal infections, congenital malformations, and child
development outcomes (43). A recent review of 17 trials (of which 15 were
conducted in low- and middle-income countries) found that maternal
supplementation with multiple micronutrients (including, among others, zinc,
iron, and folic acid) reduced the risk of low-birth-weight newborns and
small-for-gestational age infants when compared to supplemental iron with or
without folic acid (44). While multiple micronutrient supplementation would
likely benefit pregnant women with coexisting micronutrient deficiencies in low-
and middle-income countries, there is no evidence to recommend zinc
supplementation in isolation in pregnant women from any settings (43, 45).
IMPAIRED GROWTH AND DEVELOPMENT
GROWTH RETARDATION
Significant delays in linear growth and weight gain, known as growth retardation
or failure to thrive, are common features of mild zinc deficiency in children.
In the 1970s and 1980s, several randomized, placebo-controlled studies of zinc
supplementation in young children with significant growth delays were conducted
in Denver, Colorado. Modest zinc supplementation (5.7 mg/day) resulted in
increased growth rates compared to placebo (46). Several meta-analyses of growth
data from zinc intervention trials have confirmed the widespread occurrence of
growth-limiting zinc deficiency in young children, especially in low- and
middle-income countries (47-49). A 2018 systematic review and meta-analysis
identified 54 trials that examined the impact of zinc supplementation during
infancy (on average, 7.6 mg/day for 30.9 weeks) or childhood (on average, 8.5
mg/day for 38.9 weeks) on child anthropometric measurements (50). There was
evidence of a positive effect of supplemental zinc on children’s height, weight,
and weight-for-age Z score (WAZ), but neither on height-for-age Z score (HAZ) or
weight-for-height Z score (WHZ). In addition, zinc supplementation did not
reduce the risks of underweight (WAZ<-2 standard deviation [SD]), wasting
(WHZ<-2 SD), or stunting (HAZ<-2 SD) in children (50). Although the exact
mechanisms for the growth-limiting effect of zinc deficiency are not known,
research indicates that zinc availability affects cell-signaling systems that
coordinate the response to the growth-regulating hormone, insulin-like growth
factor-1 (IGF-1) (51).
DELAYED MENTAL AND PSYCHOMOTOR DEVELOPMENT IN YOUNG CHILDREN
Adequate nutrition in essential for brain growth and development, especially
during the first 1,000 days of life — a critical period of development for all
organs and systems spanning from conception to 24 months of age (52). Animal
studies have established that zinc deficiency in early life interferes with
normal brain development and cognitive functions (reviewed in 53). Data on the
effect of zinc supplementation during pregnancy on infants’ neurologic and
psychomotor outcomes is very limited. In a randomized, placebo-controlled trial
in African-American women, daily maternal supplementation with 25 mg of zinc
from about 19 weeks’ gestation had no effect on neurologic development test
scores in their children at five years of age (54).
Several studies have reported on the effect of postnatal zinc supplementation on
mental and motor development. Two early randomized controlled trials, one
conducted in India and the other in Guatemala, suggested that postnatal
supplementation with 10 mg/day of zinc resulted in toddlers being more vigorous
(55) and functionally active (56). In one trial conducted in Brazilian newborns
from low-income families and weighing between 1,500 g and 2,499 g at birth,
neither zinc supplementation for eight weeks with 1 mg/day or 5 mg/day improved
mental and psychomotor development at 6 or 12 months of age compared to a
placebo and assessed using the Bayley Scales of Infant Development (BSID) for
Mental Development Index (MDI) and Psychomotor Development Index (PDI) (57).
Additionally, a randomized, placebo-controlled, double-blind trial in Chilean
newborns (birth weights >2,300 g) from low-income families reported no effect of
zinc supplementation (5 mg/day) on mental and psychomotor development indices at
6 and 12 months (58). Two other trials found that supplemental zinc failed to
improve MDI or PDI at 12 months of age when zinc (10 mg/day) was given to
six-month-old infants for six months (59) or at the end of the intervention in
toddlers aged 12-18 months when zinc (30 mg/day) was given for four months (60).
A 2012 Cochrane review of eight clinical trials found no evidence that postnatal
zinc supplementation improves mental or motor development of infants and
children from populations with presumably inadequate zinc status (61).
IMPAIRED IMMUNE SYSTEM FUNCTION
Adequate zinc intake is essential in maintaining the integrity of the immune
system (62), specifically for normal development and function of cells that
mediate both innate (neutrophils, macrophages, and natural killer cells) and
adaptive (B-lymphocytes and T-lymphocytes) immune responses (63). Because
pathogens also require zinc to thrive and invade, a well-established
antimicrobial defense mechanism in the body sequesters free zinc away from
microbes (64). Another opposite mechanism consists in intoxicating intracellular
microbes within macrophages with excess zinc (65). Through weakening innate and
adaptive immune responses, zinc deficiency diminishes the capacity of the body
to combat pathogens (63, 64). As a consequence, zinc-deficient individuals
experience an increased susceptibility to a variety of infectious agents (66).
INCREASED SUSCEPTIBILITY TO INFECTIOUS DISEASE IN CHILDREN
Diarrhea: Zinc promotes mucosal resistance to infections by supporting the
activity of immune cells and the production of antibodies against invading
pathogens (63, 64, 67). Therefore, a deficiency in zinc increases the
susceptibility to intestinal infections and constitutes a major contributor to
diarrheal diseases in children (66). In turn, persistent diarrhea contributes to
zinc deficiency and malnutrition (66). Research indicates that zinc deficiency
may also potentiate the effects of toxins produced by diarrhea-causing bacteria
like E. coli (68). It is estimated that diarrheal diseases are responsible for
the deaths of about 500,000 children under five years of age annually in low-
and middle-income countries (69). Zinc supplementation in combination with oral
rehydration therapy has been shown to significantly reduce the duration and
severity of acute and persistent childhood diarrhea and to increase survival in
a number of randomized controlled trials (70). A 2016 meta-analysis of
randomized controlled trials found that zinc supplementation reduced the
duration of acute diarrhea by one day in children aged >6 months who presented
signs of malnutrition (5 trials; 419 children) (71). However, there was little
evidence to suggest that zinc could be as efficacious to reduce the duration of
acute diarrheal episodes in children aged <6 months and in well-nourished
children aged >6 months. Zinc supplementation also reduced the duration of
persistent diarrhea in children by more than half a day (5 trials; 529 children)
(71).
The World Health Organization (WHO) and the United Nations Children's Fund
(UNICEF) currently recommend supplementing young children with 10 to 20 mg/day
of zinc as part of the treatment for acute diarrheal episodes and to prevent
further episodes in the two to three months following zinc supplementation (72).
Pneumonia: Pneumonia — caused by lower respiratory tract viral or bacterial
infections (LRTIs) — accounts for nearly 1 million deaths among children
annually, primarily in low-and middle-income countries (69). Vaccinations
against Haemophilus influenzae type B, pneumococcus, pertussis (whooping cough),
and measles can help prevent pneumonia (73). According to a 2009 WHO report on
disease risk factors, zinc deficiency may be responsible for 13% of all LRTI
cases, primarily pneumonia and flu cases, in children younger than 5 years (74).
Accordingly, a 2016 meta-analysis of six trials found that zinc supplementation
in children under 5 years old reduced the risk of pneumonia by 13% (75).
However, it remains unclear whether supplemental zinc, in conjunction with
antibiotic therapy, is beneficial in the treatment of pneumonia. A recent
randomized, placebo-controlled trial conducted in Gambian children who were not
zinc deficient failed to show any benefit of zinc supplementation (10 mg/day or
20 mg/day [depending on child’s age] for 7 days) given alongside antibiotics in
the treatment of severe pneumonia (76). A 2018 meta-analysis of five trials
(1,822 participants) found no improvement when zinc was used as an adjunct to
antibiotic treatment in children with pneumonia (77). There was, however,
evidence that supplemental zinc reduced the risk of pneumonia-related mortality
(3 trials; 1,318 participants) (77).
Malaria: Early studies have indicated that zinc supplementation may reduce the
incidence of clinical attacks of malaria in children (78). A placebo-controlled
trial in preschool-aged children in Papua New Guinea found that zinc
supplementation reduced the frequency of health center attendance due to
Plasmodium falciparum malaria by 38% (79). Additionally, the number of malaria
episodes accompanied by high circulating parasite concentrations was reduced by
68%, suggesting that zinc supplementation may be of benefit in preventing more
severe episodes of malaria. However, a six-month trial in more than 700 West
African children did not find any difference in the frequency or severity of
malaria episodes between children supplemented with zinc and those given a
placebo (80). Another randomized controlled trial reported that zinc
supplementation did not benefit preschool-aged children with acute,
uncomplicated malaria (81). There is also little evidence to suggest that zinc
supplementation could reduce the risk of malaria-related mortality in children
(82). At present, there is not enough evidence to suggest a prophylactic and/or
therapeutic role for supplemental zinc in the management of childhood malaria
(48). A recent randomized, placebo-controlled trial did not provide clear-cut
evidence of a protective effect of zinc (25 mg/day) administered to Tanzanian
women during their first gestational trimester until delivery on the risk of
placental malaria infection (83).
AGE-RELATED DECLINE IN IMMUNE FUNCTION
Inadequate zinc status in elderly subjects is not uncommon and is thought to
exacerbate the age-related decline in immune function (84). In one study, low
serum zinc concentrations in nursing home residents were associated with higher
risks of pneumonia and pneumonia-related and all-cause mortality (85). Trials
examining the effects of zinc supplementation on immune function in middle-aged
and elderly adults have given mixed results (reviewed in 86). Some studies
showed mixed or no effects of zinc supplementation on parameters of immune
function (87-89). However, zinc supplementation was found to have a positive
impact on certain aspects of immune function that are affected by zinc
deficiency, such as the decline in T-cell (a type of lymphocyte) function (90).
For example, a randomized, placebo-controlled study in adults over 65 years of
age found that zinc supplementation (25 mg/day) for three months increased blood
concentrations of helper T-cells and cytotoxic T-cells (91). Additionally, a
randomized, double-blind, placebo-controlled trial in 101 older adults (aged
50-70 years) with normal blood zinc concentrations showed that zinc
supplementation at 15 mg/day for six months improved the helper
T-cells/cytotoxic T-cells ratio, which tends to decline with age and is a
predictor of survival (92). However, the study also suggested that a dose of 30
mg/day of zinc might reduce the number of B-lymphocytes, which play a central
role in humoral immunity. Further, zinc supplementation had no effect on various
immune parameters, including markers of inflammation, measures of granulocyte
and monocyte phagocytic capacity, or cytokine production by activated monocytes
(92).
A more recent trial examined the effect of daily supplementation with a multiple
micronutrients, including 5 mg or 30 mg of zinc for three months, on zinc status
and markers of immune function in institutionalized elderly participants (mean
age, >80 years) with low serum zinc concentrations (93). Zinc status was
improved with the 30 mg/day dose — but not with 5 mg/day — yet the most
zinc-deficient individuals failed to achieve normal serum zinc concentrations
within the intervention period. The number of circulating T-cells was also
significantly increased in those who took the micronutrient supplement with the
higher versus low dose of zinc (93).
More research is warranted before zinc supplementation could be recommended to
older adults, especially those with no symptoms of declining immunity.
Nonetheless, the high prevalence of zinc deficiency among institutionalized
elderly adults should be addressed and would likely improve the performance of
their immune systems (86).
TYPE 2 DIABETES MELLITUS
There is a close relationship between zinc and insulin action. Specifically, in
pancreatic β-cells, zinc is involved in insulin synthesis and storage in
secretory vesicles. Zinc is released with the hormone when blood glucose
concentrations increase (15). Zinc is also understood to stimulate glucose
uptake and metabolism by insulin-sensitive tissues through triggering the
intracellular insulin signaling pathway (94). Single-nucleotide polymorphisms
(SNPs) in the SLC30A8 (solute carrier family 30 member 8) gene, coding for a
zinc transporter that co-localizes with insulin in β-cells, have been associated
with higher risks of type 1 and type 2 diabetes mellitus (95), though the risk
for type 2 diabetes mellitus was found to be reduced with rare
protein-truncating variants of the gene (96). The first prospective cohort study
to examine the risk of type 2 diabetes in relation to zinc intakes — the Nurses’
Health Study (NHS) — followed 82,297 US registered female nurses for 24 years.
The data analysis showed an 8% lower risk of type 2 diabetes with the highest
versus lowest intake of dietary zinc (median values, 11.8 mg/day versus 4.9
mg/day) (97). This finding was consistent with the result of the Australian
Longitudinal Study on Women’s Health (ALSWH) that enrolled 8,921 women for six
years and showed a 50% lower risk of diabetes with the highest versus lowest
intake of energy-adjusted dietary zinc (98). Both NHS and ALSWH studies also
reported a reduced risk of diabetes with higher versus lower zinc-to-heme iron
ratios in the diet (97, 98), although the significance is unclear as nonheme
iron, rather than heme iron, is known to interfere with dietary zinc absorption
(see Nutrient interactions). Heme iron may be an indicator of red meat
consumption, which has been positively associated with the risk of type 2
diabetes (99). However, two other prospective cohort studies — the Multi-Ethnic
Study of Atherosclerosis (MESA; 4,982 participants) and the National Institutes
of Health-American Association of Retired Persons (NIH-AARP) Diet and Health
Study (232,007 participants) — failed to find evidence for an association
between zinc intake and risk of type 2 diabetes (100, 101). Another recent
prospective cohort study, the Malmo Diet and Cancer Study in 26,132 middle-aged
Swedish participants followed for 19 years, found an increased risk of diabetes
with higher dietary zinc intakes yet a lower risk of diabetes in zinc supplement
users (versus non-users) and in those with a higher zinc-to-iron intake ratio
(102). The authors reported a stronger inverse association between zinc-to-iron
intake ratio and risk of diabetes among obese participants carrying a specific
SLC30A8 genotype (102).
The results of a few short-term intervention studies suggest that zinc
supplementation may improve glucose handling in subjects with prediabetes. A
2015 systematic review identified three short trials (4 to 12 weeks) conducted
in adults with prediabetes and found little evidence of an improvement in
insulin resistance with zinc supplementation (103). However, a 2016 randomized,
placebo-controlled trial in 55 Bangladeshi with prediabetes showed that daily
supplementation with zinc sulfate (30 mg/day for 6 months) improved fasting
blood glucose, as well as measures of β-cell function and insulin sensitivity
(104). Similar observations were made in another recent trial in 100 Sri Lankan
randomized to receive daily supplementation with zinc (20 mg of elemental zinc)
or a placebo for one year (105). Supplemental zinc improved zinc status and
measures of glycemic control (105). Large-scale, long-term studies are necessary
to provide definite conclusions regarding the potential benefit of zinc
supplementation in subjects at risk of type 2 diabetes.
DISEASE TREATMENT
Doses of supplemental zinc in many of the below-mentioned clinical trials
exceeded the tolerable upper intake level (UL). Such high intake of supplemental
zinc may lead to adverse health effects with prolonged use (see Safety).
WILSON'S DISEASE
The protein, ATP7B, is responsible for the excretion of hepatic copper into the
biliary tract, and its impairment in Wilson's disease results in an increased
concentration of 'free' copper (i.e., not bound to the copper-carrying protein,
ceruloplasmin) in blood, an increased excretion of copper in the urine
(hypercupriuria), the deposition of copper in part of the cornea (forming
Kayser-Fleischer rings), and the accumulation of copper in the liver and brain
(106). This inherited condition is progressive and fatal if untreated. The
standard-of-care for symptomatic patients usually includes an initial phase
(around 2-6 months) of copper chelation with agents, such as penicillamine or
trientine (triethylenetetramine), followed by lifelong maintenance therapy with
penicillamine and/or trientine and/or zinc salts (107). Patients presenting
without symptoms can be treated with maintenance therapeutic doses of a
chelating agent or with zinc (108). Zinc-induced metallothionein in the
intestinal mucosa binds copper and prevents its absorption (see Nutrient
interactions). There is growing evidence to suggest that zinc salts are a safer,
much cheaper, and efficacious alternative to metal-chelating agents — which have
been associated with a worsening of symptoms during the initial phase of
treatment in some patients (109). The use of zinc is advocated as safe and
efficacious in both pediatric (110, 111) and adult patients (112-114).
COMMON COLD
ZINC LOZENGES
There is no proven treatment for common cold (115). The use of zinc lozenges
within 24 hours of the onset of cold symptoms, and continued intake every two to
three hours while awake until symptoms resolve, have been advocated for reducing
the duration of the common cold (116). Several clinical trials examining the
effect of zinc have been published to date. A 2012 systematic review and
meta-analysis of 13 randomized controlled trials reported that zinc
supplementation in the form of lozenges or syrup shortened the duration of cold
symptoms, but there was significant heterogeneity (inconsistent effects across
the included studies) for the primary outcomes (117). A 2013 Cochrane review
confirmed that oral zinc administrated within 24 hours of symptom onset could
reduce the duration of cold symptoms (14 trials, 1,656 participants) (118).
Subgroup analyses also suggested that oral zinc was effective regardless of the
age of participants (children or adults) and the type of zinc formulation
(gluconate/acetate lozenges or sulfate syrup). In addition, beneficial effects
on cold duration were seen in trials that provided more than 75 mg/day of zinc
but not in trials that used lower doses. The pooled analysis of five trials
found no evidence of an effect of oral zinc on the severity of cold symptoms.
The analysis of secondary trial outcomes suggested a faster resolution of
specific cold symptoms (cough, nasal congestion, nasal drainage, sore throat)
and a lower proportion of participants exhibiting cold symptoms after seven days
of treatment in zinc- versus placebo-supplemented participants (118).
Inconsistent findings among trials have been partly attributed to different
amounts of zinc released from various forms used in the lozenges (particularly
zinc acetate and zinc gluconate) (119, 120). It has been argued that the
unpleasant taste of zinc gluconate forming complexes with carbohydrates may have
led to poor compliance, thereby explaining negative trial results (119, 121).
However, when a meta-analysis was recently conducted on results from seven
trials (575 participants) that employed zinc lozenges at doses >75 mg/day, there
was no evidence of a difference in efficacy observed between trials that used
either zinc acetate (3 trials) or zinc gluconate (4 trials) (122).
With numerous well-controlled trials and meta-analyses, the efficacy of zinc
lozenges or syrup in treating common cold symptoms is no longer questionable. A
meta-analysis of seven trials recently reported a 33% reduction in the duration
of cold symptoms with the intake of zinc lozenges (>75 mg/day of elemental zinc)
(122). However, many supplemental zinc formulations available over-the-counter
have been found to release zero zinc ions (i.e., the biologically active form of
zinc) or to contain additives (e.g., magnesium, certain amino acids, citric
acid) that either cancel out the benefit of zinc or worsen cold symptoms (119).
Finally, although taking zinc lozenges for a cold every two to three hours while
awake will result in daily zinc intakes well above the tolerable upper intake
level (UL) of 40 mg/day for adults (see Safety), the use of zinc at daily doses
of 50 to 180 mg for one to two weeks has not resulted in serious side effects
(117). Bad taste and nausea were the most frequent adverse effects reported in
therapeutic trials (117). Use of zinc lozenges for prolonged periods (e.g., 6-8
weeks) is likely to result in copper deficiency (see Nutrient interactions and
Safety).
INTRANASAL ZINC (ZINC NASAL GELS AND NASAL SPRAYS)
Intranasal zinc preparations, designed to be applied directly to the nasal
epithelium (cells lining the nasal passages), are marketed as over-the-counter
cold remedies. While two placebo-controlled trials found that intranasal zinc
gluconate modestly shortened the duration of cold symptoms (123, 124), another
one found intranasal zinc to be of no benefit (125). The pooled analysis of
these three trials showed no overall benefit of intranasal zinc on the risk of
still experiencing cold symptoms by day 3 (126). The existence of a mouth-nose
biologically close electric circuit (BCEC) has been proposed to explain the
efficacy of oral rather than intranasal zinc delivery (119). Specifically, it is
suggested that the positively charged interior of the nose repels ionic zinc
(Zn2+) such that ionic zinc delivered by throat lozenges and migrating from the
mouth to the nose are more effective against rhinovirus infection than those
directly delivered into the nose (119). Of serious concern are several case
reports of individuals experiencing loss of the sense of smell (anosmia) after
using intranasal zinc as a cold remedy (127). Since zinc-associated anosmia may
be irreversible, intranasal zinc preparations should be avoided.
AGE-RELATED MACULAR DEGENERATION
Age-related macular degeneration (AMD) is a degenerative disease of the macula
and a leading cause of blindness in people aged >65 years in the US (128). The
macula is the portion of the retina in the back of the eye involved with central
vision. Zinc is hypothesized to play a role in the development of AMD for
several reasons: (1) zinc is found at high concentrations in the part of the
retina affected by AMD, (2) retinal zinc content has been shown to decline with
age, and (3) the activities of some zinc-dependent retinal enzymes have been
shown to decline with age. To date, prospective cohort studies have shown
limited evidence suggesting an association between dietary zinc intake and the
incidence of AMD (129-131).
However, an early randomized controlled trial provoked interest when it found
that 200 mg/day of zinc sulfate (81 mg/day of elemental zinc) over two years
limited the loss of vision in patients with AMD (132). Yet a later trial using
the same dose and duration found no benefit to patients with a more advanced
form of AMD in one eye (133). Small trials have generally not reported a
protective effect of vitamin and mineral supplementation on AMD (134, 135).
However, a randomized, double-blind, placebo-controlled trial in 74 patients
with AMD reported that supplementation with 50 mg/day of zinc monocysteine for
six months improved measures of macular function, including visual acuity,
contrast sensitivity, and photorecovery (136). A large randomized,
placebo-controlled trial of daily supplementation with antioxidants (500 mg of
vitamin C, 400 IU of vitamin E, and 15 mg of β-carotene) and high-dose zinc (80
mg of zinc as zinc oxide and 2 mg of copper as cupric oxide) — the Age-Related
Eye Disease Study (AREDS) — found that administration of high-dose zinc alone or
with the antioxidant combination to individuals with signs of moderate-to-severe
macular degeneration significantly reduced the risk of developing advanced
macular degeneration over a mean follow-up of 6.3 years (137). A follow-up
analysis conducted four years after the cessation of the trial in 2001,
including nearly 85% of the surviving participants, found that the benefit of
the AREDS (combined antioxidants plus zinc) formulation had persisted (138).
Indeed, the odds of developing late AMD, especially neovascular AMD, was lower
in both participants with a low risk of developing AMD and those who were at
risk and recommended to continue taking the AREDS formulation after the trial
ended. There was, however, no effect of AREDS formulation on the risk of
developing central geographic atrophy (138). Another trial, AREDS2, examined the
effect of an AREDS formulation without β-carotene and/or containing 25 mg
instead of 80 mg of zinc (139). The trial showed no apparent difference in the
risk of developing advanced AMD with the use of AREDS formulations containing
either 25 mg or 80 mg of zinc and/or β-carotene (140). A recent meta-analysis of
five trials (including the original AREDS study) confirmed the protective effect
of supplemental zinc against neovascular and advanced AMD (141).
In conclusion, the AREDS formulation combining antioxidants and zinc (25 mg or
80 mg) may delay the progression of the disease in patients with AMD. Patients,
especially smokers and those with vascular disease, are advised to discuss with
their physician the benefits versus potential harms that could be associated
with the long-term use of high-dose antioxidant vitamins and carotenoids (141).
DIABETES MELLITUS
TYPE 2 DIABETES MELLITUS
Poor glycemic control and frequent urination in patients with diabetes mellitus
may be driving urinary loss of zinc and contribute to marginal zinc deficiency
(142, 143). Yet, because of the role of zinc in β-cell function and insulin
action (see Disease Prevention), a number of randomized controlled trials have
examined whether supplementation with zinc (alone or with other minerals and
vitamins) could play a role in diabetes management, especially by improving
glycemic control in people with type 2 diabetes (15). Out of the 12 trials that
measured participants’ zinc status at baseline, supplementation with zinc
(20-240 mg/day) for 4 to 16 weeks improved fasting blood glucose in patients who
presented with zinc deficiency (6 studies). Supplemental zinc also reduced the
proportion of glycated hemoglobin (HbA1c) in two trials conducted in
zinc-deficient participants, yet not in four studies including participants
without zinc deficiency (15). Patients with type 2 diabetes should ensure that
their diet provides enough zinc to cover their needs, especially if their blood
glucose is poorly controlled.
GESTATIONAL DIABETES MELLITUS
Gestational diabetes mellitus is defined as hyperglycemia that is first
diagnosed during pregnancy. The condition is associated with an increased risk
for adverse pregnancy outcomes (144). A group of investigators in Iran conducted
two small randomized, placebo-controlled trials to examine the effect of zinc
supplementation in pregnant women with gestational diabetes. Supplemental zinc
(30 mg/day) for six weeks during pregnancy improved zinc status, reduced fasting
blood glucose, and improved insulin sensitivity in women with gestational
diabetes but had no impact on pregnancy outcomes, including the need for
cesarean section, need for insulin therapy, newborn’s birth size and Apgar
scores, or incidence of hyperbilirubinemia (145, 146). Similar improvements of
markers of glycemic control were reported in another placebo-controlled trial
that randomized pregnant women with gestational diabetes to receive zinc (4 mg)
together with magnesium (100 mg), calcium (400 mg), and vitamin D (200 IU) twice
a day for six weeks (147). There was also some evidence suggesting that
supplemental zinc might help correct other metabolic disorders (e.g., abnormal
blood lipid profile) associated with gestational diabetes (147, 148).
HIV/AIDS
Sufficient zinc is essential to maintain immune system function, and
HIV-infected individuals are particularly susceptible to zinc deficiency. In
HIV-infected patients, low serum zinc concentrations have been associated with
disease progression and increased mortality (149, 150). In one study conducted
in AIDS patients, 45 mg/day of zinc for one month resulted in a decreased
incidence of opportunistic infections compared to placebo (151). A
placebo-controlled trial in 231 HIV-positive adults with low zinc status found
that zinc supplementation (12 mg/day for women and 15 mg/day for men) for 18
months reduced the incidence of immunological failure (defined by a CD4+ count
<200 cells/mm3) by 76% and the rate of diarrhea by 60% (152). A 2011 systematic
review that identified three randomized controlled trials in primarily
resource-poor settings concluded that zinc supplementation was safe and
efficacious in reducing opportunistic infections in HIV-positive adults (153).
Evidence of benefits of zinc supplementation in HIV-positive pregnant women and
children is very limited. In a double-blind, randomized, placebo-controlled
trial in Tanzania, the administration of zinc (25 mg/day) to women between 12
and 27 weeks’ gestation until six months after delivery failed to reduce
maternal viral load or limit mother-to-child HIV transmission (154). A
randomized placebo-controlled trial of zinc supplementation (10 mg/day for 6
months) in 96 HIV-positive children (6 months to 5 years old) in South Africa
showed no effect on CD4+ count and viral load (155). There was evidence showing
a reduction in the incidence of watery diarrhea in zinc-supplemented children
compared to those taking a placebo, yet no differences in the incidence of
pneumonia, ear infection, or upper respiratory tract infection (155). Another
trial in Uganda showed that supplemental zinc in children with severe pneumonia
effectively reduced case fatality regardless of children’s HIV status (156).
While zinc supplementation during pregnancy and infancy is recommended in
populations likely to be zinc deficient (43, 71, 75), its use in HIV infection
management requires further investigation (157).
ALZHEIMER’S DISEASE
Abnormal homeostasis of trace metals, in particular copper and zinc, has been
reported in individuals affected by Alzheimer’s disease — the most common form
of dementia. Specifically, results from case-control studies have shown higher
serum copper concentrations and lower serum zinc concentrations in people with
Alzheimer’s disease compared to cognitively healthy controls (158-160). Based on
the utilization of zinc salts in Wilson's disease, it has been proposed that
zinc supplementation could improve zinc and copper status and limit further
cognitive deterioration in individuals with Alzheimer’s disease. The use of
slow-release zinc acetate (150 mg/day for six months) in a randomized,
placebo-controlled study of 60 patients with mild-to-moderate Alzheimer’s
disease corrected low zinc status and decreased serum 'free' copper (i.e.,
unbound to ceruloplasmin) (161). Moreover, when a post-hoc analysis was
restricted to participants over 70 years of age (N=29), it was found that zinc
supplementation prevented the deterioration of cognition scores over the trial
period (161). Additional evidence is needed to confirm whether zinc
supplementation could play a role in stabilizing cognitive deficits in older
adults with dementia.
DEPRESSION
A data analysis of the Boston Area Community Health (BACH) survey, including
3,708 participants (ages, 30-79 years), reported higher odds of depression
symptoms in women (but not in men) in the lowest versus highest quartiles of
total (median values, 8.7 mg/day versus 26.8 mg/day) and dietary (median values,
7.6 mg/day versus 13.1 mg/day) zinc intakes (162). The possibility that zinc
could play a role in preventing or alleviating depression has been explored in
two trials conducted by one research group. The data from these trials were
analyzed following a per-protocol approach (i.e., restricted to the participants
who completed the studies). A preliminary randomized, double-blind,
placebo-controlled trial in 20 subjects (mean age, 43 years) treated for major
depression showed that supplementation with 25 mg/day of zinc reduced depression
symptoms at 6 and 12 weeks as assessed by the Hamilton Depression Rating Scale
(HDRS) and Beck Depression Inventory (BDI) scores (163). A second
placebo-controlled trial in 60 participants treated with the antidepressant
imipramine (Tofranil; 100-200 mg/day) assessed the therapeutic response to
supplemental zinc (25 mg/day) using HDRS, BDI, Clinical Global Impression scale
(CGI), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores (164). Zinc
supplementation improved score-based measures of therapeutic response and
remission after six weeks but only when the analysis was restricted to
participants resistant to imipramine. There was, however, no evidence of an
effect of zinc after 12 weeks (164).
NEONATAL SEPSIS
Sepsis is a life-threatening condition that causes organ dysfunction as a
consequence of a dysregulated host’s response to infection (165). Sepsis is
accompanied by changes in zinc homeostasis characterized in particular by a
decrease in serum zinc concentration and an increase in liver zinc concentration
(166). These changes in zinc distribution are thought to be part of a host’s
defense mechanism whereby the host can limit zinc availability to pathogens, as
well as stimulate the immune system. Such a mechanism has been described for
other transition metals, including iron and manganese (167). However, lower
serum zinc concentrations in critically ill patients at high risk of organ
failure have been associated with recurrent sepsis episodes and poorer outcomes
(168, 169). A 2018 systematic review identified four trials that examined the
effect of zinc supplementation in newborns with sepsis (166). Zinc
supplementation was found to result in decreased inflammation (170) and better
neurological development (171, 172). Three out of four trials that examined the
rate of mortality showed no effect of zinc supplementation (170, 172, 173).
SOURCES
FOOD SOURCES
Shellfish, beef, and other red meats are rich sources of zinc; nuts and legumes
are relatively good plant sources of zinc. Zinc bioavailability (the fraction of
zinc retained and used by the body) is relatively high in meat, eggs, and
seafood because of the relative absence of compounds that inhibit zinc
absorption and the presence of sulfur-containing amino acids (cysteine and
methionine) that improve zinc absorption. Zinc in whole-grain products and plant
proteins is less bioavailable due to their relatively high content of phytate,
which inhibits zinc absorption (174). The enzymatic action of yeast reduces the
level of phytate in foods; therefore, leavened whole-grain breads have more
bioavailable zinc than unleavened whole-grain breads.
National dietary surveys in the US estimate that average dietary zinc intake
from naturally and fortified food is about 12.3 mg/day in adults, with about 12%
of the adult population being at risk for inadequate intake (175). The zinc
content of some foods relatively rich in zinc is listed in Table 2 in milligrams
(mg). For more information on the nutrient content of specific foods, search
USDA's FoodData Central (176).
Table 2. Some Food Sources of Zinc Food Serving Zinc (mg) Oyster, cooked 6
medium 27-50 Beef, chuck, blade roast, cooked 3 ounces* 8.7 Beef, ground, 90%
lean meat, cooked 3 ounces 5.4 Crab, Dungeness, cooked 3 ounces 4.7 Fortified,
whole-grain toasted oat cereal 1 cup 3.8 Turkey, dark meat, cooked 3 ounces 3.0
Pork, loin, blade roast, cooked 3 ounces 2.7 Soybeans, dry roasted ½ cup 2.2
Chicken, roasting, dark meat, cooked 3 ounces 1.8 Pine nuts 1 ounce 1.8 Cashews
1 ounce 1.6 Yogurt, plain, low fat 6 ounces 1.5 Sunflower seed kernels 1 ounce
1.5 Pecans 1 ounce 1.3 Brazil nuts 1 ounce 1.2 Chickpeas (garbanzo beans),
cooked ½ cup 1.2 Milk 1 cup (8 fl. oz.) 1.1 Cheese, cheddar 1 ounce 1.0 Almonds
1 ounce 0.9 Beans, baked ½ cup 0.9 *A three-ounce serving of meat is about the
size of a deck of cards.
SUPPLEMENTS
A number of zinc supplements are commercially available, including zinc acetate,
zinc gluconate, zinc picolinate, and zinc sulfate. Zinc picolinate has been
promoted as a more absorbable form of zinc, but there are few data to support
this idea in humans. Limited work in animals suggests that increased intestinal
absorption of zinc picolinate may be offset by increased elimination (29).
SAFETY
TOXICITY
ACUTE TOXICITY
Isolated outbreaks of acute zinc toxicity have occurred as a result of the
consumption of food or beverages contaminated with zinc released from galvanized
containers. Signs of acute zinc toxicity are abdominal pain, diarrhea, nausea,
and vomiting. Single doses of 225 to 450 mg of zinc usually induce vomiting.
Milder gastrointestinal distress has been reported at doses of 50 to 150 mg/day
of supplemental zinc. Metal fume fever has been reported after the inhalation of
zinc oxide fumes. Specifically, profuse sweating, weakness, and rapid breathing
may develop within eight hours of zinc oxide inhalation and persist for 12 to 24
hours after exposure is terminated (6, 29).
ADVERSE EFFECTS
The major consequence of long-term consumption of excessive zinc is copper
deficiency. Total zinc intakes of 60 mg/day (50 mg supplemental and 10 mg
dietary zinc) for up to 10 weeks have been found to result in signs of copper
deficiency (29). Copper deficiency has also been reported following chronic use
of excessive amounts of zinc-containing denture creams (≥2 tubes per week
containing 17-34 mg/g of zinc) (177). In order to prevent copper deficiency, the
US Food and Nutrition Board set the tolerable upper intake level (UL) for adults
at 40 mg/day, including dietary and supplemental zinc (Table 3) (29).
Table 3. Tolerable Upper Intake Level (UL) for Zinc Age Group UL (mg/day)
Infants 0-6 months 4 Infants 7-12 months 5 Children 1-3 years 7 Children 4-8
years 12 Children 9-13 years 23 Adolescents 14-18 years 34 Adults 19 years and
older 40
INTRANASAL ZINC
Intranasal zinc is known to cause a loss of the sense of smell (anosmia) in
laboratory animals (178), and there have been several case reports of
individuals who developed anosmia after using intranasal zinc gluconate (127).
Since zinc-associated anosmia may be irreversible, the use of zinc nasal gels
and sprays should be avoided.
DRUG INTERACTIONS
The use of zinc supplements decreases the absorption of certain medications,
including cephalexin (Keplex) and penicillamine (Cuprimine, Depen), as well as
the antiretroviral drugs atazanavir (Reyataz) and ritonavir (Norvir) (179).
Concomitant administration of zinc supplements with certain medications like
tetracycline and quinolone antibiotics may decrease the absorption of both zinc
and the medications, potentially reducing drug efficacy. Taking zinc supplements
and these medications at least two hours apart should prevent this interaction.
The therapeutic use of metal-chelating agents, such as penicillamine (used to
treat copper overload in Wilson's disease) and diethylenetriamine pentaacetate
(DTPA; used to treat iron overload), has resulted in severe zinc deficiency.
Anticonvulsant drugs, especially sodium valproate, may also precipitate zinc
deficiency. Prolonged use of diuretics may increase urinary zinc excretion,
resulting in increased loss of zinc. Because supplemental zinc can lower blood
glucose, those taking anti-diabetic agents are advised to use zinc supplements
with caution.
LINUS PAULING INSTITUTE RECOMMENDATION
The RDA for zinc (8 mg/day for adult women and 11 mg/day for adult men) appears
sufficient to prevent deficiency in most individuals, but the lack of sensitive
indicators of zinc nutritional status in humans makes it difficult to determine
the level of zinc intake most likely to promote optimum health. Following the
Linus Pauling Institute recommendation to take a multivitamin/mineral supplement
will generally provide at least the RDA for zinc. Daily total (supplemental +
dietary) intakes of zinc should not exceed the UL (40 mg/day for adults) in
order to limit the risk of copper deficiency in particular (see Safety).
OLDER ADULTS (>50 YEARS)
Although the requirement for zinc is not known to be higher for older adults,
many have inadequate dietary zinc intakes (180, 181). A reduced capacity to
absorb zinc, increased likelihood of disease states that alter zinc utilization,
and increased use of drugs that decrease zinc bioavailability may all contribute
to an increased risk of mild zinc deficiency in older adults. Adequate dietary
intake of zinc is essential for older adults because the consequences of mild
zinc deficiency, such as impaired immune system function, are especially
relevant to maintenance of their health.
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AUTHORS AND REVIEWERS
Originally written in 2001 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in December 2003 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in October 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in June 2013 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in February 2019 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University
Reviewed in May 2019 by:
Emily Ho, Ph.D.
Endowed Director, Moore Family Center for Whole Grain Foods,
Nutrition and Preventive Health
Professor, School of Biological and Population Health Sciences
Principal Investigator, Linus Pauling Institute
Oregon State University
Copyright 2001-2022 Linus Pauling Institute
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* Vitamins
* Minerals
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* Potassium
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