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NCP Miracle II
161 Richardson-Bass Rd
Kenly, NC 27542
Tel:(919)284-6002 Fax:(919)284-4197
EMail: info1@ncpmiracle2.com
161 Richardson-Bass Rd
Kenly, NC 27542
Tel:(919)284-6002 Fax:(919)284-4197
EMail: info1@ncpmiracle2.com
| Zinc |
Zinc
Over 300 enzymes in the body need zinc to order to function properly; is needed to make
important antioxidant enzymes; is essential for protein synthesis and collagen formation;
governs the contractibility of muscles; helps in the formation of insulin; helps prevent
macular degeneration (one of the most common causes of vision loss in the elderly), and
helps prevent the onset of cataracts; important for blood stability; exerts a normalizing
effect on the prostate and is important in the development of all reproductive organs; is
critical in the male sex drive and is involved in hormone metabolism, sperm formation and
sperm motility; helps prevent and reduces the length and severity of the common .cold;
helps decrease cholesterol deposits; helps heal stomach ulcers, relieves symptoms of
rheumatoid arthritis; prevents acne outbreaks, and regulates the activity of oil glands;
promotes a healthy immune system and the healing of wounds; has shown to be important in
brain function and in the treatment of schizophrenia; makes your fingernails strong and gets
rid of white spots on your nails; helps prevent cancer sores, loss of appetite, taste and
smell problems, dermatitis, and binge-eating; believed to retard the aging process.
Zinc is an essential trace element for all forms of life. The significance of zinc in human
nutrition and public health was recognized relatively recently. Clinical zinc deficiency in
humans was first described in 1961, when the consumption of diets with low zinc
bioavailability due to high phytic acid 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
developing countries (2).
Function
Numerous aspects of cellular metabolism are zinc-dependent. Zinc plays important roles in
growth and development, the immune response, neurological function, and reproduction.
On the cellular level, the function of zinc can be divided into three categories: 1) catalytic, 2)
structural, and 3) regulatory (3).
Catalytic role
Nearly 100 different enzymes depend on zinc for their ability to catalyze vital chemical
reactions. Zinc-dependent enzymes can be found in all known classes of enzymes (4).
Structural role
Zinc plays an important role in the structure of proteins and cell membranes. A finger-like
structure, known as a zinc finger motif, stabilizes the structure of a number of proteins. For
example, copper provides the catalytic activity for the antioxidant enzyme copper-zinc
superoxide dismutase (CuZnSOD), while zinc plays a critical structural role (4, 5). The
structure and function of cell membranes are also affected by zinc. Loss of zinc from
biological membranes increases their susceptibility to oxidative damage and impairs their
function (6).
Regulatory role
Zinc finger proteins have been found to regulate gene expression by acting as transcription
factors (binding to DNA and influencing the transcription of specific genes). Zinc also plays a
role in cell signaling and has been found to influence hormone release and nerve impulse
transmission. Recently zinc has been found to play a role in apoptosis (gene-directed cell
death), a critical cellular regulatory process with implications for growth and development,
as well as a number of chronic diseases (7).
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. Metallothionein traps copper within intestinal cells
and prevents its systemic absorption (see Copper). More typical intakes of zinc do not affect
copper absorption and high copper intakes do not affect zinc absorption (5).
Iron
Supplemental (38-65 mg/day of elemental iron) but not dietary levels of iron may decrease
zinc absorption. 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 more than 60 mg/day of elemental
iron (8, 9).
Calcium
High levels of dietary calcium impair zinc absorption in animals, but it is uncertain whether
this occurs in humans. 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 (10), but 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 (11). Calcium in combination
with phytic acid reduces zinc absorption. This effect is particularly relevant to individuals
consuming a diet that is highly dependent on tortillas made with lime (calcium oxide). For
more information on phytic acid, see Food Sources.
Folic acid
The bioavailability of dietary folate is increased by the action of a zinc-dependent enzyme,
suggesting a possible interaction between zinc and folic acid. In the past, some studies
found low zinc intake to decrease folate absorption, while other studies found folic acid
supplementation to impair zinc utilization in individuals with marginal zinc status (4, 5).
However, a more recent study found that supplementation with a relatively high dose of
folic acid (800 mcg/day) for 25 days did not alter zinc status in a group of students being fed
low-zinc diets (3.5 mg/day), nor did zinc intake impair folate utilization (12).
DEFICIENCY
Severe 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. 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 corneas, 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 (5, 13). Although 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, may also result in severe
zinc deficiency.
Mild zinc deficiency
More recently, it has become apparent that milder zinc deficiency contributes to a number
of health problems, especially common in children who live in developing countries. The
lack of a sensitive indicator of mild zinc deficiency hinders the scientific study of its health
implications. However, controlled trials of moderate zinc supplementation have
demonstrated that mild zinc deficiency contributes to impaired physical and
neuropsychological development, and increased susceptibility to life-threatening
infections in young children (13). For a more detailed discussion of the relationship of zinc
deficiency to health problems, see Disease Prevention.
Individuals at risk of zinc deficiency: (5)
• Infants and children
• Pregnant and lactating (breastfeeding) women, especially teenagers
• 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
• Individuals with alcoholic liver disease have increased urinary zinc excretion and low
liver zinc levels
• Individuals with sickle cell anemia
• Older adults (65 years and older)
• Strict vegetarians: The requirement for dietary zinc may be as much as fifty percent
greater for strict vegetarians whose major food staples are grains and legumes because
high levels of phytic acid in these foods reduce the absorption of zinc (4) (see Food
Sources).
The Recommended Dietary Allowance (RDA)
The U.S. recommended dietary allowances (RDA) for zinc are listed for all age groups
because infants, children, 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 was 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 (4).
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
Breastfeeding 18 years and younger 13
Breastfeeding 19 years and older - 12
PREVENTION OF DISEASES RELATED TO ZINC DEFICIENCY
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 (14).
More recently, a number of larger studies in developing countries observed similar results
with modest zinc supplementation. A meta-analysis of growth data from zinc intervention
trials recently confirmed the widespread occurrence of growth limiting zinc deficiency in
young children, especially in developing countries (15). Although the exact mechanism for
the growth limiting effects of zinc deficiency are not known, recent 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) (16).
Delayed neurological and behavioral development in young children
Low maternal zinc nutritional status has been associated with diminished attention in the
newborn infant and poorer motor function at 6 months of age. Zinc supplementation has
been associated with improved motor development in very low-birth-weight infants, more
vigorous activity in Indian infants and toddlers, and more functional activity in Guatemalan
infants and toddlers (17). Additionally, zinc supplementation was associated with better
neuropsychologic functioning (e.g., attention) in Chinese first grade students, but only
when zinc was provided with other micronutrients (18). Two other studies failed to find an
association between zinc supplementation and measures of attention in children diagnosed
with growth retardation. Although initial studies suggest that zinc deficiency may depress
cognitive development in young children, more controlled research is required to
determine the nature of the effect and whether zinc supplementation is beneficial (19).
Impaired immune system function
Adequate zinc intake is essential in maintaining the integrity of the immune system (20), and
zinc deficient individuals are known to experience increased susceptibility to a variety of
infectious agents (21).
Increased susceptibility to infectious disease in children
Diarrhea: It is estimated that diarrheal diseases result in the deaths of over 3 million
children in developing countries each year. The adverse effects of zinc deficiency on
immune system function are likely to increase the susceptibility of children to infectious
diarrhea, while persistent diarrhea contributes to zinc deficiency and malnutrition. Recent
research indicates that zinc deficiency may also potentiate the effects of toxins produced by
diarrhea-causing bacteria like E. coli (22). 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 (23).
Pneumonia: Zinc supplementation may also reduce the incidence of lower respiratory
infections, such as pneumonia. A pooled analysis of a number of studies in developing
countries demonstrated a substantial reduction in the prevalence of pneumonia in children
supplemented with zinc (24).
Malaria: Several studies have indicated that zinc supplementation may reduce the incidence
of clinical attacks of malaria in children (25). A placebo-controlled trial in preschool children
in Papua New Guinea found that zinc supplementation reduced the frequency of health
center attendance due to plasmodium falciparum malaria by 38% (26). Additionally, the
number of malaria episodes accompanied by high blood levels of the malaria-causing
parasite were reduced by 68%, suggesting that zinc supplementation may be of benefit in
preventing more severe episodes of malaria. However, a 6-month trial in more than 700
west African children did not find the frequency or severity of malaria episodes caused by P.
falciparum to be different in children supplemented with zinc compared to those given a
placebo (27).
Immune response in the elderly
Age-related declines in immune function are similar to those associated with zinc deficiency,
and the elderly represent a group that is vulnerable to mild zinc deficiency. However, the
results of zinc supplementation trials on immune function in the elderly have been mixed.
Certain aspects of immune function in the elderly have been found to improve with zinc
supplementation (28). For example, a randomized placebo-controlled study in men and
women over 65 years of age found that a zinc supplement of 25 mg/day for 3 months
increased levels of some circulating immune cells (CD4 T-cells and cytotoxic T-lymphocytes)
compared to placebo (29). However, other studies have not found zinc supplementation to
improve parameters of immune function, indicating that more research is required before
any recommendations regarding zinc and immune system response in the elderly can be
made.
Pregnancy complications
It has been estimated that 82% of pregnant women worldwide are likely to have inadequate
zinc intakes. Poor maternal zinc nutritional status has been associated with a number of
adverse outcomes of pregnancy, including low birth weight, premature delivery, and labor
and delivery complications. However, the results of maternal zinc supplementation trials in
the U.S. and developing countries have been mixed (17). Although some studies have found
maternal zinc supplementation to increase birth weight and decrease the likelihood of
premature delivery, two recent studies in Peruvian and Bangladeshi women found no
difference between zinc supplementation and placebo in the incidence of low birth weight
or premature delivery (30, 31). Supplementation studies designed to examine the effect of
zinc supplementation on labor and delivery complications have also generated mixed
results, though few have been conducted in zinc deficient populations (17).
Disease Treatment
Common cold
Zinc lozenges
The use of zinc lozenges within 24 hours of the onset of cold symptoms and continued
every 2-3 hours while awake until symptoms resolve has been advocated for reducing the
duration of the common cold. At least ten controlled trials of zinc gluconate lozenges for the
treatment of common colds in adults have been published. Five studies found that zinc
lozenges reduced the duration of cold symptoms, while five studies found no difference
between zinc lozenges and placebo lozenges with respect to the duration or severity of
cold symptoms. A recent meta-analysis of published randomized controlled trials on the use
of zinc gluconate lozenges in colds found that evidence for their effectiveness in reducing
the duration of common colds was still lacking (32). Two clinical trials examined the effect of
zinc acetate lozenges on cold symptoms. While one study found that zinc acetate lozenges
(12.8 mg of zinc per lozenge) taken every 2-3 hours while awake reduced the duration of
overall cold symptoms (4.5 vs. 8.1 days) compared to placebo (33), another study found zinc
acetate lozenges no different than placebo in reducing the duration or severity of cold
symptoms (34).
Despite numerous well-controlled clinical trials, the efficacy of zinc lozenges in treating
common cold symptoms remains questionable. The physiological basis for a beneficial effect
of high-dose zinc supplementation on cold symptoms is not known. Taking zinc lozenges
every 2-3 hours while awake often results in daily zinc intakes well above the tolerable
upper level of intake (UL) of 40 mg/day (see Safety). Short-term use of zinc lozenges (e.g.,
five days) has not resulted in serious side effects, though some individuals experienced
gastrointestinal disturbances and mouth irritation. Use of zinc lozenges for prolonged
periods (e.g., 6-8 weeks) is likely to result in copper deficiency. For this reason, some
experts have recommended that a person who does not show clear evidence of
improvement of cold symptoms after 3-5 days of zinc lozenge treatment seek medical
evaluation (33
.
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 also marketed as over-the-counter cold remedies. While two
placebo-controlled trials found that intranasal zinc gluconate modestly shortened the
duration of cold symptoms (35, 36), two other placebo-controlled studies found intranasal
zinc to be of no benefit (37, 38). In the most rigorously controlled of these studies, intranasal
zinc gluconate did not affect the severity or duration of cold symptoms in volunteers
inoculated with rhinovirus, a common cause of colds (37). Of concern are several case
reports of individuals experiencing loss of the sense of smell (anosmia) after using
intranasal zinc as a cold remedy (39, 40). Since zinc-associated anosmia may be irreversible,
intranasal zinc preparations should be avoided.
Age-related macular degeneration
A leading cause of blindness in people over the age of 65 in the U.S. is a degenerative
disease of the macula, known as age-related macular degeneration (AMD). In the back of the
eye, the macula is the portion of the retina involved with central vision. Zinc is hypothesized
to play a role in the development of AMD for several reasons: 1) zinc is found in 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 activity of some zinc-dependent retinal enzymes has
been shown to decline with age. However, scientific evidence that zinc intake is associated
with the development or progression of AMD is limited. Observational studies have not
demonstrated clear associations between dietary zinc intake and the incidence of AMD (41-
43). A randomized controlled trial provoked interest when it found that 200 mg/day of zinc
sulfate (81 mg/day of elemental zinc) over 2 years reduced the loss of vision in patients with
AMD (44). However, a later trial using the same dose and duration found no beneficial effect
in patients with a more advanced form of AMD in one eye (45). A large randomized controlled
trial of daily antioxidant (500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of beta carotene)
and high-dose zinc (80 mg of zinc and 2 mg of copper) supplementation found that the
antioxidant combination plus high-dose zinc and high-dose zinc alone significantly reduced
the risk of advanced macular degeneration compared to placebo in individuals with signs of
moderate to severe macular degeneration in at least one eye (46). At present, there is little
evidence that zinc supplementation would be beneficial to people with early signs of
macular degeneration, but further randomized controlled trials are warranted (47).
Diabetes mellitus
Moderate zinc deficiency may be relatively common in individuals with diabetes mellitus.
Increased urinary zinc excretion appears to contribute to the marginal zinc nutritional status
that has been observed in diabetics (48). Although zinc supplementation has been reported
to improve immune function in diabetics, zinc supplementation of 50 mg/day adversely
affected control of blood glucose in insulin-dependent (type 1) diabetics (49). More recently,
supplementation of type 2 diabetics with 30 mg/day of zinc for 6 months reduced a non-
specific measure of oxidative stress (plasma TBARS), without significantly affecting blood
glucose control (50). Presently, the influence of zinc on glucose metabolism requires further
study before high-dose zinc supplementation can be advocated for diabetics (5).
HIV/AIDS
Sufficient zinc is essential in maintaining immune system function and HIV infected
individuals are particularly susceptible to zinc deficiency. Decreased serum zinc levels have
been associated with more advanced disease and increased mortality in HIV patients (51,
52). In one of the few zinc supplementation studies conducted in AIDS patients, 45 mg/day of
zinc for one month resulted in a decreased incidence in opportunistic infections compared
to placebo (53). However, the HIV virus also requires zinc, and excessive zinc intake may
stimulate the progression of HIV infection. In an observational study of HIV-infected men,
increased zinc intake was associated with more rapid disease progression and any intake of
zinc supplements was associated with poorer survival (54). These results indicate that
further research is necessary to determine optimal zinc intakes for HIV-infected individuals
(20).
Sources
Food sources
Shellfish, beef, and other red meats are rich sources of zinc. Nuts and legumes are
relatively good plant sources. 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 certain amino acids (cysteine
and methionine) that improve zinc absorption. The zinc in whole grain products and plant
proteins is less bioavailable due to their relatively high content of phytic acid, a compound
that inhibits zinc absorption (5). The enzymatic action of yeast reduces the level of phytic
acid in foods. Therefore, leavened whole grain breads have more bioavailable zinc than
unleavened whole grain breads. Recently, national dietary surveys in the U.S. estimated that
the average dietary zinc intake was 9 mg/day for adult women and 13 mg/day for adult men
(4). The zinc content of some relatively zinc-rich foods is listed in milligrams (mg) in the table
below. For more information on the nutrient content of foods you eat frequently, search the
USDA food composition database.
Food Serving Zinc (mg)
Oysters 6 medium (cooked) 43.4
Crab, Dungeness 3 ounces (cooked) 4.6
Beef 3 ounces* (cooked) 5.8
Pork 3 ounces (cooked) 2.2
Chicken (dark meat) 3 ounces (cooked) 2.4
Turkey (dark meat) 3 ounces (cooked) 3.5
Yogurt, fruit 1 cup (8 ounces) 1.8
Cheese, cheddar 1 ounce 0.9
Milk 1 cup (8 ounces) 1.0
Cashews 1 ounce 1.6
Almonds 1 ounce 1.0
Peanuts 1 ounce 0.9
Beans, baked 1/2 cup 1.8
Chickpeas (garbanzo beans) 1/2 cup 1.3
*A three-ounce serving of meat is about the size of a deck of cards.
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. Profuse sweating, weakness, and rapid
breathing may develop within 8 hours of zinc oxide inhalation and persist 12-24 hours after
exposure is terminated (4, 5).
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) have been
found to result in signs of copper deficiency. In order to prevent copper deficiency, the U.S.
Food and Nutrition Board set the tolerable upper level of intake (UL) for adults at 40 mg/day,
including dietary and supplemental zinc (4).
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 year 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
(55), and there have been several case reports of individuals who developed anosmia after
using intranasal zinc gluconate (39, 40). Since zinc-associated anosmia may be irreversible,
zinc nasal gels and nasal sprays should be avoided.
Drug Interactions
Concomitant administration of zinc supplements and certain antibiotics, specifically
tetracyclines and quinolones, may decrease absorption of the antibiotic with potential
reduction of its efficacy. Taking zinc supplements and these antibiotics at least two hours
apart should prevent this interaction (56). The therapeutic use of metal chelating (binding)
agents like penicillamine (used to treat copper overload in Wilson's disease) and
diethylenetriamine pentaacetate or 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. The tuberculosis medication, ethambutol, has metal
chelating properties and has been shown to increase zinc loss in rats (5).
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/multimineral supplement containing 100% of the daily values (DV) of most
nutrients will generally provide 15 mg/day in of zinc in addition to that in foods.
Adults over the age of 65
Although the requirement for zinc is not known to be higher for older adults, their average
zinc intake tends to be considerably less than the RDA. A reduced capacity to absorb zinc,
increased likelihood of disease states that alter zinc utilization, and increased use of drugs
that increase zinc excretion may contribute to an increased risk of mild zinc deficiency in
older adults. Because the consequences of mild zinc deficiency, such as impaired immune
system function, are particularly relevant to the health of older adults, they should pay
particular attention to maintaining adequate zinc intake.
Over 300 enzymes in the body need zinc to order to function properly; is needed to make
important antioxidant enzymes; is essential for protein synthesis and collagen formation;
governs the contractibility of muscles; helps in the formation of insulin; helps prevent
macular degeneration (one of the most common causes of vision loss in the elderly), and
helps prevent the onset of cataracts; important for blood stability; exerts a normalizing
effect on the prostate and is important in the development of all reproductive organs; is
critical in the male sex drive and is involved in hormone metabolism, sperm formation and
sperm motility; helps prevent and reduces the length and severity of the common .cold;
helps decrease cholesterol deposits; helps heal stomach ulcers, relieves symptoms of
rheumatoid arthritis; prevents acne outbreaks, and regulates the activity of oil glands;
promotes a healthy immune system and the healing of wounds; has shown to be important in
brain function and in the treatment of schizophrenia; makes your fingernails strong and gets
rid of white spots on your nails; helps prevent cancer sores, loss of appetite, taste and
smell problems, dermatitis, and binge-eating; believed to retard the aging process.
Zinc is an essential trace element for all forms of life. The significance of zinc in human
nutrition and public health was recognized relatively recently. Clinical zinc deficiency in
humans was first described in 1961, when the consumption of diets with low zinc
bioavailability due to high phytic acid 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
developing countries (2).
Function
Numerous aspects of cellular metabolism are zinc-dependent. Zinc plays important roles in
growth and development, the immune response, neurological function, and reproduction.
On the cellular level, the function of zinc can be divided into three categories: 1) catalytic, 2)
structural, and 3) regulatory (3).
Catalytic role
Nearly 100 different enzymes depend on zinc for their ability to catalyze vital chemical
reactions. Zinc-dependent enzymes can be found in all known classes of enzymes (4).
Structural role
Zinc plays an important role in the structure of proteins and cell membranes. A finger-like
structure, known as a zinc finger motif, stabilizes the structure of a number of proteins. For
example, copper provides the catalytic activity for the antioxidant enzyme copper-zinc
superoxide dismutase (CuZnSOD), while zinc plays a critical structural role (4, 5). The
structure and function of cell membranes are also affected by zinc. Loss of zinc from
biological membranes increases their susceptibility to oxidative damage and impairs their
function (6).
Regulatory role
Zinc finger proteins have been found to regulate gene expression by acting as transcription
factors (binding to DNA and influencing the transcription of specific genes). Zinc also plays a
role in cell signaling and has been found to influence hormone release and nerve impulse
transmission. Recently zinc has been found to play a role in apoptosis (gene-directed cell
death), a critical cellular regulatory process with implications for growth and development,
as well as a number of chronic diseases (7).
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. Metallothionein traps copper within intestinal cells
and prevents its systemic absorption (see Copper). More typical intakes of zinc do not affect
copper absorption and high copper intakes do not affect zinc absorption (5).
Iron
Supplemental (38-65 mg/day of elemental iron) but not dietary levels of iron may decrease
zinc absorption. 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 more than 60 mg/day of elemental
iron (8, 9).
Calcium
High levels of dietary calcium impair zinc absorption in animals, but it is uncertain whether
this occurs in humans. 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 (10), but 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 (11). Calcium in combination
with phytic acid reduces zinc absorption. This effect is particularly relevant to individuals
consuming a diet that is highly dependent on tortillas made with lime (calcium oxide). For
more information on phytic acid, see Food Sources.
Folic acid
The bioavailability of dietary folate is increased by the action of a zinc-dependent enzyme,
suggesting a possible interaction between zinc and folic acid. In the past, some studies
found low zinc intake to decrease folate absorption, while other studies found folic acid
supplementation to impair zinc utilization in individuals with marginal zinc status (4, 5).
However, a more recent study found that supplementation with a relatively high dose of
folic acid (800 mcg/day) for 25 days did not alter zinc status in a group of students being fed
low-zinc diets (3.5 mg/day), nor did zinc intake impair folate utilization (12).
DEFICIENCY
Severe 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. 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 corneas, 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 (5, 13). Although 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, may also result in severe
zinc deficiency.
Mild zinc deficiency
More recently, it has become apparent that milder zinc deficiency contributes to a number
of health problems, especially common in children who live in developing countries. The
lack of a sensitive indicator of mild zinc deficiency hinders the scientific study of its health
implications. However, controlled trials of moderate zinc supplementation have
demonstrated that mild zinc deficiency contributes to impaired physical and
neuropsychological development, and increased susceptibility to life-threatening
infections in young children (13). For a more detailed discussion of the relationship of zinc
deficiency to health problems, see Disease Prevention.
Individuals at risk of zinc deficiency: (5)
• Infants and children
• Pregnant and lactating (breastfeeding) women, especially teenagers
• 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
• Individuals with alcoholic liver disease have increased urinary zinc excretion and low
liver zinc levels
• Individuals with sickle cell anemia
• Older adults (65 years and older)
• Strict vegetarians: The requirement for dietary zinc may be as much as fifty percent
greater for strict vegetarians whose major food staples are grains and legumes because
high levels of phytic acid in these foods reduce the absorption of zinc (4) (see Food
Sources).
The Recommended Dietary Allowance (RDA)
The U.S. recommended dietary allowances (RDA) for zinc are listed for all age groups
because infants, children, 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 was 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 (4).
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
Breastfeeding 18 years and younger 13
Breastfeeding 19 years and older - 12
PREVENTION OF DISEASES RELATED TO ZINC DEFICIENCY
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 (14).
More recently, a number of larger studies in developing countries observed similar results
with modest zinc supplementation. A meta-analysis of growth data from zinc intervention
trials recently confirmed the widespread occurrence of growth limiting zinc deficiency in
young children, especially in developing countries (15). Although the exact mechanism for
the growth limiting effects of zinc deficiency are not known, recent 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) (16).
Delayed neurological and behavioral development in young children
Low maternal zinc nutritional status has been associated with diminished attention in the
newborn infant and poorer motor function at 6 months of age. Zinc supplementation has
been associated with improved motor development in very low-birth-weight infants, more
vigorous activity in Indian infants and toddlers, and more functional activity in Guatemalan
infants and toddlers (17). Additionally, zinc supplementation was associated with better
neuropsychologic functioning (e.g., attention) in Chinese first grade students, but only
when zinc was provided with other micronutrients (18). Two other studies failed to find an
association between zinc supplementation and measures of attention in children diagnosed
with growth retardation. Although initial studies suggest that zinc deficiency may depress
cognitive development in young children, more controlled research is required to
determine the nature of the effect and whether zinc supplementation is beneficial (19).
Impaired immune system function
Adequate zinc intake is essential in maintaining the integrity of the immune system (20), and
zinc deficient individuals are known to experience increased susceptibility to a variety of
infectious agents (21).
Increased susceptibility to infectious disease in children
Diarrhea: It is estimated that diarrheal diseases result in the deaths of over 3 million
children in developing countries each year. The adverse effects of zinc deficiency on
immune system function are likely to increase the susceptibility of children to infectious
diarrhea, while persistent diarrhea contributes to zinc deficiency and malnutrition. Recent
research indicates that zinc deficiency may also potentiate the effects of toxins produced by
diarrhea-causing bacteria like E. coli (22). 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 (23).
Pneumonia: Zinc supplementation may also reduce the incidence of lower respiratory
infections, such as pneumonia. A pooled analysis of a number of studies in developing
countries demonstrated a substantial reduction in the prevalence of pneumonia in children
supplemented with zinc (24).
Malaria: Several studies have indicated that zinc supplementation may reduce the incidence
of clinical attacks of malaria in children (25). A placebo-controlled trial in preschool children
in Papua New Guinea found that zinc supplementation reduced the frequency of health
center attendance due to plasmodium falciparum malaria by 38% (26). Additionally, the
number of malaria episodes accompanied by high blood levels of the malaria-causing
parasite were reduced by 68%, suggesting that zinc supplementation may be of benefit in
preventing more severe episodes of malaria. However, a 6-month trial in more than 700
west African children did not find the frequency or severity of malaria episodes caused by P.
falciparum to be different in children supplemented with zinc compared to those given a
placebo (27).
Immune response in the elderly
Age-related declines in immune function are similar to those associated with zinc deficiency,
and the elderly represent a group that is vulnerable to mild zinc deficiency. However, the
results of zinc supplementation trials on immune function in the elderly have been mixed.
Certain aspects of immune function in the elderly have been found to improve with zinc
supplementation (28). For example, a randomized placebo-controlled study in men and
women over 65 years of age found that a zinc supplement of 25 mg/day for 3 months
increased levels of some circulating immune cells (CD4 T-cells and cytotoxic T-lymphocytes)
compared to placebo (29). However, other studies have not found zinc supplementation to
improve parameters of immune function, indicating that more research is required before
any recommendations regarding zinc and immune system response in the elderly can be
made.
Pregnancy complications
It has been estimated that 82% of pregnant women worldwide are likely to have inadequate
zinc intakes. Poor maternal zinc nutritional status has been associated with a number of
adverse outcomes of pregnancy, including low birth weight, premature delivery, and labor
and delivery complications. However, the results of maternal zinc supplementation trials in
the U.S. and developing countries have been mixed (17). Although some studies have found
maternal zinc supplementation to increase birth weight and decrease the likelihood of
premature delivery, two recent studies in Peruvian and Bangladeshi women found no
difference between zinc supplementation and placebo in the incidence of low birth weight
or premature delivery (30, 31). Supplementation studies designed to examine the effect of
zinc supplementation on labor and delivery complications have also generated mixed
results, though few have been conducted in zinc deficient populations (17).
Disease Treatment
Common cold
Zinc lozenges
The use of zinc lozenges within 24 hours of the onset of cold symptoms and continued
every 2-3 hours while awake until symptoms resolve has been advocated for reducing the
duration of the common cold. At least ten controlled trials of zinc gluconate lozenges for the
treatment of common colds in adults have been published. Five studies found that zinc
lozenges reduced the duration of cold symptoms, while five studies found no difference
between zinc lozenges and placebo lozenges with respect to the duration or severity of
cold symptoms. A recent meta-analysis of published randomized controlled trials on the use
of zinc gluconate lozenges in colds found that evidence for their effectiveness in reducing
the duration of common colds was still lacking (32). Two clinical trials examined the effect of
zinc acetate lozenges on cold symptoms. While one study found that zinc acetate lozenges
(12.8 mg of zinc per lozenge) taken every 2-3 hours while awake reduced the duration of
overall cold symptoms (4.5 vs. 8.1 days) compared to placebo (33), another study found zinc
acetate lozenges no different than placebo in reducing the duration or severity of cold
symptoms (34).
Despite numerous well-controlled clinical trials, the efficacy of zinc lozenges in treating
common cold symptoms remains questionable. The physiological basis for a beneficial effect
of high-dose zinc supplementation on cold symptoms is not known. Taking zinc lozenges
every 2-3 hours while awake often results in daily zinc intakes well above the tolerable
upper level of intake (UL) of 40 mg/day (see Safety). Short-term use of zinc lozenges (e.g.,
five days) has not resulted in serious side effects, though some individuals experienced
gastrointestinal disturbances and mouth irritation. Use of zinc lozenges for prolonged
periods (e.g., 6-8 weeks) is likely to result in copper deficiency. For this reason, some
experts have recommended that a person who does not show clear evidence of
improvement of cold symptoms after 3-5 days of zinc lozenge treatment seek medical
evaluation (33
.
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 also marketed as over-the-counter cold remedies. While two
placebo-controlled trials found that intranasal zinc gluconate modestly shortened the
duration of cold symptoms (35, 36), two other placebo-controlled studies found intranasal
zinc to be of no benefit (37, 38). In the most rigorously controlled of these studies, intranasal
zinc gluconate did not affect the severity or duration of cold symptoms in volunteers
inoculated with rhinovirus, a common cause of colds (37). Of concern are several case
reports of individuals experiencing loss of the sense of smell (anosmia) after using
intranasal zinc as a cold remedy (39, 40). Since zinc-associated anosmia may be irreversible,
intranasal zinc preparations should be avoided.
Age-related macular degeneration
A leading cause of blindness in people over the age of 65 in the U.S. is a degenerative
disease of the macula, known as age-related macular degeneration (AMD). In the back of the
eye, the macula is the portion of the retina involved with central vision. Zinc is hypothesized
to play a role in the development of AMD for several reasons: 1) zinc is found in 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 activity of some zinc-dependent retinal enzymes has
been shown to decline with age. However, scientific evidence that zinc intake is associated
with the development or progression of AMD is limited. Observational studies have not
demonstrated clear associations between dietary zinc intake and the incidence of AMD (41-
43). A randomized controlled trial provoked interest when it found that 200 mg/day of zinc
sulfate (81 mg/day of elemental zinc) over 2 years reduced the loss of vision in patients with
AMD (44). However, a later trial using the same dose and duration found no beneficial effect
in patients with a more advanced form of AMD in one eye (45). A large randomized controlled
trial of daily antioxidant (500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of beta carotene)
and high-dose zinc (80 mg of zinc and 2 mg of copper) supplementation found that the
antioxidant combination plus high-dose zinc and high-dose zinc alone significantly reduced
the risk of advanced macular degeneration compared to placebo in individuals with signs of
moderate to severe macular degeneration in at least one eye (46). At present, there is little
evidence that zinc supplementation would be beneficial to people with early signs of
macular degeneration, but further randomized controlled trials are warranted (47).
Diabetes mellitus
Moderate zinc deficiency may be relatively common in individuals with diabetes mellitus.
Increased urinary zinc excretion appears to contribute to the marginal zinc nutritional status
that has been observed in diabetics (48). Although zinc supplementation has been reported
to improve immune function in diabetics, zinc supplementation of 50 mg/day adversely
affected control of blood glucose in insulin-dependent (type 1) diabetics (49). More recently,
supplementation of type 2 diabetics with 30 mg/day of zinc for 6 months reduced a non-
specific measure of oxidative stress (plasma TBARS), without significantly affecting blood
glucose control (50). Presently, the influence of zinc on glucose metabolism requires further
study before high-dose zinc supplementation can be advocated for diabetics (5).
HIV/AIDS
Sufficient zinc is essential in maintaining immune system function and HIV infected
individuals are particularly susceptible to zinc deficiency. Decreased serum zinc levels have
been associated with more advanced disease and increased mortality in HIV patients (51,
52). In one of the few zinc supplementation studies conducted in AIDS patients, 45 mg/day of
zinc for one month resulted in a decreased incidence in opportunistic infections compared
to placebo (53). However, the HIV virus also requires zinc, and excessive zinc intake may
stimulate the progression of HIV infection. In an observational study of HIV-infected men,
increased zinc intake was associated with more rapid disease progression and any intake of
zinc supplements was associated with poorer survival (54). These results indicate that
further research is necessary to determine optimal zinc intakes for HIV-infected individuals
(20).
Sources
Food sources
Shellfish, beef, and other red meats are rich sources of zinc. Nuts and legumes are
relatively good plant sources. 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 certain amino acids (cysteine
and methionine) that improve zinc absorption. The zinc in whole grain products and plant
proteins is less bioavailable due to their relatively high content of phytic acid, a compound
that inhibits zinc absorption (5). The enzymatic action of yeast reduces the level of phytic
acid in foods. Therefore, leavened whole grain breads have more bioavailable zinc than
unleavened whole grain breads. Recently, national dietary surveys in the U.S. estimated that
the average dietary zinc intake was 9 mg/day for adult women and 13 mg/day for adult men
(4). The zinc content of some relatively zinc-rich foods is listed in milligrams (mg) in the table
below. For more information on the nutrient content of foods you eat frequently, search the
USDA food composition database.
Food Serving Zinc (mg)
Oysters 6 medium (cooked) 43.4
Crab, Dungeness 3 ounces (cooked) 4.6
Beef 3 ounces* (cooked) 5.8
Pork 3 ounces (cooked) 2.2
Chicken (dark meat) 3 ounces (cooked) 2.4
Turkey (dark meat) 3 ounces (cooked) 3.5
Yogurt, fruit 1 cup (8 ounces) 1.8
Cheese, cheddar 1 ounce 0.9
Milk 1 cup (8 ounces) 1.0
Cashews 1 ounce 1.6
Almonds 1 ounce 1.0
Peanuts 1 ounce 0.9
Beans, baked 1/2 cup 1.8
Chickpeas (garbanzo beans) 1/2 cup 1.3
*A three-ounce serving of meat is about the size of a deck of cards.
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. Profuse sweating, weakness, and rapid
breathing may develop within 8 hours of zinc oxide inhalation and persist 12-24 hours after
exposure is terminated (4, 5).
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) have been
found to result in signs of copper deficiency. In order to prevent copper deficiency, the U.S.
Food and Nutrition Board set the tolerable upper level of intake (UL) for adults at 40 mg/day,
including dietary and supplemental zinc (4).
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 year 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
(55), and there have been several case reports of individuals who developed anosmia after
using intranasal zinc gluconate (39, 40). Since zinc-associated anosmia may be irreversible,
zinc nasal gels and nasal sprays should be avoided.
Drug Interactions
Concomitant administration of zinc supplements and certain antibiotics, specifically
tetracyclines and quinolones, may decrease absorption of the antibiotic with potential
reduction of its efficacy. Taking zinc supplements and these antibiotics at least two hours
apart should prevent this interaction (56). The therapeutic use of metal chelating (binding)
agents like penicillamine (used to treat copper overload in Wilson's disease) and
diethylenetriamine pentaacetate or 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. The tuberculosis medication, ethambutol, has metal
chelating properties and has been shown to increase zinc loss in rats (5).
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/multimineral supplement containing 100% of the daily values (DV) of most
nutrients will generally provide 15 mg/day in of zinc in addition to that in foods.
Adults over the age of 65
Although the requirement for zinc is not known to be higher for older adults, their average
zinc intake tends to be considerably less than the RDA. A reduced capacity to absorb zinc,
increased likelihood of disease states that alter zinc utilization, and increased use of drugs
that increase zinc excretion may contribute to an increased risk of mild zinc deficiency in
older adults. Because the consequences of mild zinc deficiency, such as impaired immune
system function, are particularly relevant to the health of older adults, they should pay
particular attention to maintaining adequate zinc intake.