2012 06 18 phc zinc final final

8/16/2019 2012 06 18 Phc Zinc Final Final

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Overview of Zinc


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TABLE OF CONTENTS

Acknowledgements .............................................................................................................. 3

Document guide .................................................................................................................... 4

Take home points: zinc summary chart ................................................................................ 5

A trace mineral ...................................................................................................................... 9

Historical perspective ............................................................................................................ 9

Functions and deficiencies .................................................................................................. 9Functions ................................................................................................................. 10Consequences of deficiency .................................................................................... 10Zinc-dependent cellular functions ............................................................................ 10Immune function and wound healing ....................................................................... 11Normal growth and development / growth and development of nervous system andneurological functions .............................................................................................. 13Sexual maturity and reproduction ............................................................................ 14Normal blood sugar balance and metabolic rate ..................................................... 14Proper appetite, sense of taste and smell ................................................................ 14

Age-related macular degeneration ........................................................................... 15

Symptoms of deficiency ...................................................................................................... 15

Individuals most at risk ....................................................................................................... 16


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Acknowledgements

The creation of this zinc training module would not have been possible without thecontribution of numerous sites and organizations. Specifically, the Linus Pauling Institute;the National Institutes of Health’s Office of Dietary Supplements (NIH / ODS); Wardlaw,Hampl, and DiSilvestro’s 2004 sixth edition of Perspectives in Nutrition; and TuftsUniversity’s Friedman School of Nutrition Science and Policy Introduction to HumanNutrition course (McKay, Fall 2004). Special thanks to the Flour Fortification Initiative (FFI)for their willingness to share the material on their website.

This zinc module is the third in a series of micronutrient modules adapted from an internalorganizational training program developed by Project Healthy Children (PHC). Thematerial is intended to provide the reader with an in-depth look at the major micronutrientsgenerally targeted in nutrition interventions to ensure a detailed understanding of how thenutrients work and why they are important. Previous modules include vitamin A and iron;subsequent modules cover zinc and iodine.

For any questions regarding the material, please contact Project Healthy Children’sDirector of Nutrition Programming, Laura Rowe, at [email protected].


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Document guide: suggestions on how to tackle this module

This document has been structured so that it delivers information in the same way as the

previous modules. Therefore, a similar warning pertains: reading through this entiredocument in one day may be dangerous!

Divide up the document and the time you have to read it so that you are only going througha few sections at a time. This will help you to get through it in a more manageable way.The ‘tackling technique’ is the same as that outlined for the other modules:

Each section is followed by a ‘quick recap’ to summarize main points and provide a

convenient way of returning to each section for review. However, reading the entiredocument is advised as diagrams attempt to make potentially confusing points clearer andexplain the ‘why’ behind much of what we already know about zinc.

If you understand the content included in the ‘take home points: zinc summary chart’ andthe ‘quick recaps’ you will have retained the nuts and bolts of this module. If you would likefurther explanation any of the module’s cited sources are good to review.

Please note this information is not intended to be used as individual nutritional guidance. It

is meant only to be used as education material.


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Take home points: zinc summary chart

Functions andfunctionalexplanations

• Numerous zinc-dependent enzymes exist that affect proteinstructure and synthesis, replication of DNA and RNA,regulations of gene activity, cell division and activation

o Required by more enzymes in the body than all traceminerals combined. Needed to catalyze chemicalreactions; ensure proteins and cell membranes workproperly; read DNA instructions; ensure cell signaling,hormone release, and nerve impulse transmission.

• Immune function and wound healingo Low zinc status = poor thymic development. A poorly

developed thymus = weak T-cells that are unable torecognize and fight off infection, impacting rates ofdiarrhea and respiratory tract infections.

o Due to zinc’s role in maintaining skin and mucusmembranes, zinc is important for wound healing.

o

Zinc and the common cold: zinc prevents thereplication of rhinovirus (a common cause of colds).

• Normal growth and development during pregnancy,childhood, and adolescence / growth and development ofthe nervous system and neurological functions

o Affects the growth-regulating hormone IGF-1. Withoutzinc, this growth hormone cannot do its job leading tostunted growth in young children.

o Bone growth is affected due to zinc-dependentenzymes and hormones required for bonedevelopment.

o If a pregnant woman is zinc deficient, the fetus can


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thyroid hormone without adequate zinc or iron.

• Proper appetite, sense of taste and smello We need the protein gustin, found in the saliva, in

order to taste. Gustin needs zinc to function. Sincesmell and taste are connected, deficiency causesimpaired sense of taste and smell.

• Proper functioning of the retinao Zinc prevents cellular damage to the retina. A lack of

zinc = poor retina and macula functioning(responsible for central vision).

o Zinc in the retina decreases with age impactingvision.

o Zinc is needed to convert retinol to retinal allowing forproper night vision.

Consequences ofdeficiency

• Contributes to 800,000 child deaths / year due to zinc’simpact on immune functions. Global estimates indicate that~1/3 of the world’s population live in countries where the riskof zinc deficiency is high

•

Diarrhea rates are linked to insufficient levels of zinc withdiarrhea causing 18% or 3 million child deaths a year

• Causes dwarfism due to zinc’s impact on growth anddevelopment

• Impairs vitamin A metabolism contributing to vit A deficiency

Symptoms ofdeficiency

• Impaired taste and smell, hair loss, loss of appetite,diarrhea, delayed sexual maturity, growth retardation /stunting in children, mental lethargy, night blindness.

Individuals most atrisk

• Aside from diets low in zinc, deficiency is common whendiets are high in phytates. Soaking beans, grains, and seedswill activate natural phytases, which deactivate phytates.Those most at risk include:


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Sources • Bioavailability is higher in animal products due to theabsence of compounds that inhibit absorption (i.e. phytatesand oxalates) and the presence of certain amino acids (i.e.

cysteine and methionine) that improve absorption.• Good animal sources: goat, beef, shellfish, liver, eggs.

• Good plant sources: whole grains, peanuts, legumes. Breastmilk is a good source of zinc for the infant but is not affectedby maternal status.

• Supplements are recommended by WHO and UNICEF totreat acute childhood diarrhea.

RecommendedDaily Allowance(RDA)

•

RDA for adolescents and adults: 8-11 mg/day; 11-13mg/day for pregnant and lactating women (higher forlactating). Infants 0-6 months: 2mg/day; infants 7-12months: 3 mg/day.

Toxicity symptoms • UL is based on when zinc begins to interfere with copper. Acopper deficiency can reduce HDL (good cholesterol) levels.

• UL for adult: 40 mg/day

• Too much zinc can also interfere with iron causing anemia.

• Symptoms of overload: abdominal pain, diarrhea, vomiting.Nutrient-nutrientinteractions andinterconnectedness

• Zinc and vitamin A: zinc is needed by retinal binding protein(RBP). Therefore, a lack of zinc = a lack of vitamin A totissues in need. Zinc is needed to convert retinol into retinal

– retinal is needed to create rhodopsin, the protein in theeye that absorbs light. Therefore, a lack of zinc = potentialfor night blindness.

• Zinc and copper: high zinc = copper is trapped and not ableto be absorbed = lowers levels of HDL.

• Zinc and iron: too much zinc can decrease iron absorptioncausing anemia. Too much iron can decrease zinc


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phytases by soaking or allowing to ferment / germinate.

• The addition of animal sources also improves absorption.

Measurement

indicators /biomarkers

• Few reliable biomarkers for zinc deficiency exit to date.

• Serum and plasma zinc are the most common indicatorsused. A big down side is that plasma zinc decreases duringpregnancy, protein-energy malnutrition (PEM), and infection.

• Proxy indicators are used in lieu of a lack of reliablebiomarkers and include:

o Prevalence of inadequate intakes of zinc (throughdietary surveys) > 25%

o HAZ for children under the age of five > 20%.o A high prevalence of diarrhea is also often used as a

proxy indictor, although there is no designated cut-offat this point in time.


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A Trace Mineral1 Zinc is a trace mineral, which, as you may recall, means it holds the following properties ofall trace minerals:

Historical perspective2,3

Zinc was recognized as an essential nutrient for animals in the 1900s. However, thesignificance of zinc in human nutrition was not recognized until 1961, when in Egypt andIran it was determined that a zinc deficiency was the cause of growth retardation andinadequate sexual development in humans. However, the diet of these populations wasnot actually that low in zinc. The factor at play was a diet high in phytates that caused lowzinc bioavailability. Consuming mostly unleavened bread meant little zinc was absorbed

since yeast fermentation (used to leaven bread) significantly reduces the effect of phyticacid. Parasitic infections among these populations also contributed to the severe zincdeficiency.

Trace Mineral General Properties

1. Named because your body only requires very small amounts of them (lessthan 100mg/day) to function properly.

2. Although trace minerals constitute less than 1% of all minerals in the body,they are dietary essentials that have specified biological functions.

3. Includes: iron, zinc, manganese, copper, fluoride, molybdenum, iodine,

chromium and selenium.4. Plant sources are dependent on the soil content. If the soil is poor or low in a

mineral, the plant will be too.5. Animal sources are, in general, better absorbed.6. Dietary deficiency produces physiological or structural abnormalities.7. All minerals assist in energy metabolism.


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1. Numerous zinc-dependent enzymes exist that affect protein structure and synthesis,replication of DNA and RNA, regulations of gene activity, cell division and activation

2. Immune function and wound healing through the production of antibodies

3. Growth and development of the nervous system and neurological functions4. Normal growth and development during pregnancy, childhood, and adolescence5. Sexual maturity and reproduction6. Normal blood sugar balance and metabolic rate7. Proper appetite, sense of taste and smell8. Proper functioning of the retina

Consequences of deficiency

If the body does not receive adequate zinc, the consequences can be severe:

Consequences of zinc deficiency , , ,

• Contributes to 800,000 child deaths / year due to zinc’s impact on immunefunctions. Global estimates indicate that ~1/3 of the world’s population lives incountries where the risk of zinc deficiency is high. (CDC)

•

Diarrhea rates are linked to insufficient levels of zinc with diarrhea causing 18% or3 million child deaths year. (CDC, MI, Investing in the future)

• Causes dwarfism due to zinc’s impact on growth and development (NIH/ODS)

• Impairs vitamin A metabolism, thereby contributing to vitamin A deficiency

Zinc supplementation in combination with ORT (oral rehydration therapy) has shown toreduce the incidence of diarrhea in children by 27%, acute lower respiratory infection by15%, and mortality by 6%, in addition to significantly reducing the incidence of stunting12.

What is the connection?

Zinc-dependent cellular functions13,14


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influence hormone release and nerve impulse transmission. In terms of DNA, zinc isneeded to read genetic instructions. A lack of zinc = DNA instructions get misread.

Quick-recap: Zinc is required by more enzymes in the body than all trace mineralscombined. Zinc is needed to catalyze chemical reactions, to ensure proteins and cellmembranes work properly, to read DNA instructions, to ensure cell signaling, and toensure hormone release and nerve impulse transmission.

Immune function and wound healing 15,16,17,18

“Zinc has shown the most specific and in many ways the strongest effect on the function ofthe immune system of any micronutrient”, Cunningham-Rundles, Cornell University

Medical School.

In order to develop and activate T-lymphocyte cells – the body’s defense against infectionand bacteria – zinc must be present in sufficient quantities; hence the connection betweena lack of zinc and increased susceptibility to infection. How does it work? Although theexact mechanisms behind the relationship between zinc and immunity are still up fordebate, several hypotheses have been made.

First, let’s take a quick look at how the immune system is built: After birth, all immunesystem-specific cells appear first in the bone marrow. Some of these cells will have thepotential ability to recognize “self” from “non-self” (i.e. the difference between healthy cellsand infectious agents). However to gain the ability to recognize healthy cells from non-healthy cells, the cells must first become “educated” on how to do so. This “education”occurs in the thymus – a gland critical to the development of the immune system since it“educates” future fighter cells. After circulating through the thymus, cells emerge as active

(“educated”) Thymus lymphocyte cells or T-cells, for short.


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So where does zinc come into play?

Since zinc is a structural component of the thymichormone, low zinc status means poor thymic development. A poorly developed thymusleads to reduced and weak T-cells (since T-cells mature in the thymus) that are unable torecognize and fight off infection. In other words, the body requires zinc to develop andactivate T-lymphocytes since thymic weakness is induced by zinc deficiency leading toincreased susceptibility to infections, particularly in children. So T-cells can’t be ‘educated’without sufficient zinc.

Two other plausible connections between zinc and immune function are 1) zinc’s role incontrolling lymphocyte cell death (otherwise known as apoptosis), irregular death oflymphocyte cells negatively impacts immune functioning, and 2) the fact that zinc is a


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respiratory tract infections after zinc supplementation.

Finally, zinc has the ability to reduce the severity and duration of the common cold by

inhibiting the binding and preventing the replication of a virus called rhinovirus (a commoncause of colds) in the mucus of the nose and by suppressing inflammation. A recentCochrane review indicates that zinc is best at reducing colds when taken within 24 hoursof the onset of symptoms. Further research is needed, however, on optimal dosage, zincformulations, and duration of treatment.19

Quick-recap: Low zinc status = poor thymic development. A poorly developed thymus =weak T-cells that are unable to recognize and fight off infection. Due to zinc’s role inmaintaining skin and mucus membranes, zinc is important for wound healing. Zinc’simpact on the immune system is what makes it so interconnected to rates of diarrhea andrespiratory tract infections. Zinc prevents the replication of the rhinovirus (a common causeof colds).

Normal growth and development during pregnancy, childhood, and adolescence / Growthand development of the nervous system and neurological functions 20,21,22

Although the exact mechanism behind zinc’s role in limiting and / or stunting growth is notfully understood, recent research indicates that zinc affects cell-signaling systems thatcoordinate the response to the growth-regulating hormone (IGF-1). In other words, thegrowth hormone cannot do its job without zinc. This leads to stunted growth in youngchildren. Severe zinc deficiency can also affect bone growth due to the large number ofenzymes and hormones required for bone development that are dependent on zinc.

If a pregnant woman is zinc deficient, the fetus can experience growth retardation in utero.

Zinc deficiency in utero can adversely affect the child’s long-term immune functioning.Impacts of maternal zinc deficiency can also be seen on the child’s neurological andbehavioral development. Low maternal zinc status has been associated with diminishedattention in newborns and poor motor function at 6 months of age.


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Sexual maturity and reproduction23,24

Zinc plays a significant role in ensuring normal sexual maturity due to its role in celldivision and protein synthesis – both connected to growth. The health of the prostate

gland, in particular, is dependent on adequate zinc levels. This is because the prostatecontains a high percentage of zinc and requires adequate zinc for normal functioning. Atthe same time, a zinc deficiency predisposes the prostate to infection. Zinc is also neededto manufacture testosterone, may have a role in hormonal functions of various endocrineorgans, and may ensure healthy sperm. How? Low zinc levels prevent the pituitary glandfrom releasing hormones required to stimulate testosterone production. Moderate zincdeficiency leads to delayed puberty in adolescents and hypogonadism (when the sex

gland produces little to no hormones) in males.

Quick-recap: Zinc is required for the normal functioning of the prostate gland, tomanufacture testosterone, and to ensure healthy sperm. This is because zinc is needed forthe pituitary gland to release hormones needed for testosterone production. Zincdeficiency in adolescents can lead to delayed puberty.

Normal blood sugar balance and metabolic rate25

In order for our bodies to maintain a sufficient insulin response, zinc is required. Insulin is ahormone made in the pancreas that moves sugar from our bloodstream into our cells. Adecrease in zinc = a decrease in insulin response = destabilized blood sugar levels.Similarly, zinc is required to maintain a normal metabolic rate. A decrease in adequate zinclevels = a decrease in our metabolic rate (in other words the rate at which our bodycreates and uses energy decreases). Finally, low levels of zinc = decreased hormonaloutput by the thyroid gland. Recall that thyroid hormones are needed to direct braindevelopment. Therefore zinc’s role in limiting thyroid hormone release may also be linked

to the neurological effects of zinc deficiency.

Based on zinc’s effect on the thyroid hormone, zinc deficiency, like iron deficiency, canhave a similar detrimental effect on the consumption of iodized salt If someone is iron and


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can only work properly, however, if zinc is present since gustin is a zinc-binding protein.Without sufficient quantities of zinc, gustin can’t do its job of allowing us to taste. Sincesmell is connected to taste, zinc deficiency causes impaired taste and smell.

Quick-recap: We need gustin in order to taste. Gustin needs zinc to function. Since smelland taste are connected, zinc deficiency causes impaired taste and smell.

Age-related macular degeneration27

Although the interconnectedness of zinc and vitamin A will be outlined later, it is worthnoting here due to the impact it has on theprevention of night blindness and age-related

macular degeneration – a leading cause ofblindness in people over the age of 65 in the US.(The macula is the portion of the retina in the backof the eye involved in central vision). It has beensuggested that zinc (along with other antioxidants)delays the progression of age-related maculardegeneration (AMD) and vision loss by preventingcellular damage to the retina and, therefore, themacula. Additionally, zinc is required for the enzymethat converts retinol to retinal (recall, retinal is

needed to create rhodopsin, the protein in the eye that allows light to be absorbed).Therefore, zinc deficiency can contribute to night blindness.

Let’s look at this a bit closer. There are three specific links that zinc has to AMD: 1) zinc isfound in high concentrations in the part of the retina affected by AMD or the macula,

therefore, a lack of sufficient zinc would impact functioning, 2) retinal zinc content hasbeen shown to decrease with age, and 3) the activities of some zinc-dependent retinalenzymes have been shown to decrease with age. So, a lack of zinc impacts thefunctioning of the retina and the macula responsible for central vision AND zinc content in


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loss of appetite, impaired immune function (frequent colds and infections), hair loss,diarrhea, delayed sexual maturity, impotence, hypogonadism in males (when the sex glandproduces little to no hormones), eye and skin lesions, weight loss, mental lethargy, night

blindness, swelling and clouding of the corneas, and behavioral disturbances. Oral zinctherapy can address many of these symptoms.

It is now understood that mild zinc deficiency contributes to several health problems inchildren, particularly in developing country settings, including stunting, impaired physicaland neuropsychological development, and increased susceptibility to infections. The lackof a sensitive indicator to measure mild zinc deficiency, however, hinders further study.

Quick-recap: Impaired taste and smell, hair loss, loss of appetite, diarrhea, delayed sexualmaturity, growth retardation / stunting in children, mental lethargy, night blindness.

Individuals most at risk of deficiency31,32,33

Primary risk factors for zinc deficiency include diets low in zinc or high in phytates,malabsorption disorders (including intestinal parasites and diarrhea), impaired utilization ofzinc, and genetic disorders. Those most at risk include:

Pre-term infantsPre-term infants are at risk of zinc deficiency for the same reason outlined for iron (recallthat iron is stored up by the infant during the last trimester; the same is true for infants andzinc), however, the extent of this kind of zinc deficiency has not been well studied.

Pregnant and lactating womenDue to high zinc requirements by the fetus, pregnant women are at an increased risk of

becoming zinc deficient. This is particularly the case when starting pregnancy withmarginal zinc status. Similarly, lactation can deplete maternal zinc stores.

Older infants (7-12 months of age)


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For vegetarians, the dietary zinc requirement may be as much as 50% higher due to highlevels of phytic acid found in grains and legumes. Ithas been suggested, however, that vegetarians

adapt to low zinc intake by reducing zinc excretionwhile increasing zinc absorption. A few techniquesused to increase zinc bioavailability in the diet ofvegetarians include soaking beans, grains, andseeds in water for several hours before cookingthem and allowing them to sit after soaking untilsprouts form (soaking activates phytases in thesefood, which deactivates phytates). Vegetarians can

also increase their zinc intake by consuming moreleavened grain products (such as bread) than unleavened products (such as crackers)since leavening breaks down phytates.

Alcoholics Alcoholics are at an increased risk of zinc deficiency for two reasons: 1) alcohol decreasesthe body’s ability to absorb zinc, and 2) alcohol increases urinary zinc excretion.

Individuals with HIV/AIDSSufficient zinc levels are particularly critical for individuals with HIV for two reasons: 1) inorder to maintain adequate immune functioning, and 2) because individuals with HIV havean increased susceptibility to zinc deficiency. Low serum levels of zinc have beenassociated with a more advanced stage of the disease and increased mortality. However,there have been mixed outcomes to studies looking at zinc supplementation among thosewith HIV. In one study, the incidence of opportunistic infections decreased after one month

of 45mg/day among AIDS patients. Yet in another study, increased zinc intake wasassociated with more rapid disease progression and poorer survival. This is due to the factthat the HIV virus actually requires zinc and any excess zinc intake may stimulate theprogression of the infection Further research is obviously needed to ensure the right


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- Individuals with protein-energy malnutrition and anorexia nervosa- Individuals with severe or persistent diarrhea: leads to excessive loss of zinc- Individuals with malabsorption syndromes, including celiac disease

- Individuals with diabetes: due to frequent urination experienced by those withdiabetes whereby zinc is lost, moderate zinc deficiency is relatively common. Zincsupplementation among this population, however, needs further study as the impacton glucose levels is not yet known

- Individuals with inflammatory bowel disease, including Crohn’s disease, ulcerativecolitis, and short bowel disease: these conditions can decrease zinc absorption andincrease zinc losses primarily from the GI tract and, to a lesser extent, from thekidney

Quick-recap: Aside from diets low in zinc, deficiency is common when diets are high in phytates. Soaking beans, grains, and seeds will activate natural phytases, whichdeactivate phytates. Those most at risk include: preterm infants since zinc is stored upduring the last trimester; pregnant and lactating women since the fetus requires high levelsof zinc; infants older than 6 months who are still breastfeeding since breast milk providessufficient zinc for the first 4-6 months of life only; individuals with sickle cell anemia,HIV/AIDS, malabsorption problems, older adults, and alcoholics (alcohol decreases the

body’s ability to absorb zinc and increases excretion).

Absorption, transport, and storage in the body34

Zinc’s pathway of absorption, transport, and storage in the body is very similar to that ofiron. After zinc is consumed from food, absorption occurs in the small intestine. When zincis absorbed into intestinal cells, it induces the synthesis of metallothionein – a protein thatbinds zinc. (Metallothionein and zinc are analogous to ferritin and iron – both serve asbinding and storage mechanisms). And zinc must be bound for the same protectivereasons that iron must be bound. That is, free roaming zinc can promote free radicals thatdamage cells and can lead to cancer. Zinc is stored (temporarily) in metallothionein.However, there are no permanent stores of zinc in the body.


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Like iron, absorption occurs most efficiently from animal products, when body needs arehigh, and when small amounts are consumed.

Quick-recap: Zinc is absorbed in the small intestine and binds to the storage proteinmetallothionein. (Zinc must be bound or else it can cause free radicals that can damagecells). If the body does not need zinc, it is sloughed off along with dead cells and excreted


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Food Serving Zinc (mg)

Oysters 6 medium (cooked) 76.3

Beef 3 ounces (cooked) 6.0

Crab, Dungeness 3 ounces (cooked) 4.7

Turkey (dark meat) 3 ounces (cooked) 3.8

Whole grain wheat flour 1 cup 3.5

Sesame seeds ! cup 2.8

Pumpkin seeds, raw ! cup 2.6

Pork 3 ounces (cooked) 2.2

Chicken (dark meat) 3 ounces (cooked) 1.8Yogurt 1 cup (8 ounces) 1.8

Milk 1 cup (8 ounces) 1.8

Cashews 1 ounce 1.6

Almonds 1 ounce 1.0

Beans, baked 1/2 cup 1.8

Chickpeas (garbanzo beans) 1/2 cup 1.3

Spinach, boiled 1 cup 1.4Green peas, boiled 1 cup 1.9

Eggs, hardboiled 1 1.4Source: Linus Pauling Institute

OK, that’s good to know but how many of the foods listed above does one really find in alow consumption (i.e. developing country) setting? Not many. So let’s look at some morerelevant foods and their zinc content.38

Food Serving Zinc (mg)

Goat meat, cooked, roasted 1 piece / 340 g 17.9 (119% DV)


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Recent studies have demonstrated the importance of zinc in reducing stunting, diarrhea,and child mortality in addition to having a positive impact on the duration of pregnancy anda reduction in premature delivery.

WHO guidelines for therapeutic supplementation of zinc

Age group Dose and Duration

Children less than six months with diarrhea 10 mg/day for 10-14 days

Children older than six months with diarrhea 20 mg/day for 10-14 days

Pregnant women 20-90 mg/day

A number of zinc supplements are available, including zinc acetate, zinc gluconate, zincpicolinate, and zinc sulfate. WHO and UNICEF now recommend short-term zincsupplementation (20 mg of zinc per day for children older than six months, or 10 mg forinfants under 6 months, for 10–14 days) to treat acute childhood diarrhea.

Quick-recap: The bioavailability of zinc is higher in animal products due to the absence ofcompounds that inhibit absorption (i.e. phytates and oxalates) and the presence of certainamino acids (i.e. cysteine and methionine) that improve absorption. Good animal sources:

goat, beef, shellfish, liver, eggs. Good plant sources: whole grains, peanuts, legumes.Breast milk is a good source of zinc for the infant but is not affected by maternal status.Supplements are recommended by WHO and UNICEF to treat acute childhood diarrhea.

Variability of requirements across populations and recommended dosage41 Since a sensitive indicator of zinc status is not currently available, the RDA for zinc isbased on a wide range of zinc-status indicators.

The Recommended Dietary Allowance (RDA) for Zinc

Life Stage Age Males (mg/day) Females (mg/day)

Infants 0 6 months 2 (AI) 2 (AI)


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months: 3 mg/day.

Toxicity42,43

The primary consequence of long-term consumption of excessive zinc (total zinc intakes of60 mg/day [50 mg supplemental and 10 mg dietary zinc] for several weeks) is copperdeficiency. Since zinc and copper compete for similar pathways, over-supplementation ofzinc can cause low copper levels, which can have detrimental effects on thecardiovascular system by reducing levels of HDL (good cholesterol).

Similarly, since zinc and iron (elemental iron from supplements, not dietary iron) competewith one another for absorption, excessive intake of zinc could lead to impaired iron status

and, therefore, anemia.

Symptoms of acute toxicity, such as when food or beverages contaminated with zinc fromgalvanized containers are consumed, include abdominal pain, diarrhea, nausea, andvomiting. Single doses of 225 to 450 mg of zinc usually induce vomiting. Milder GI distresshas been reported at doses of 50 to 150 mg/day of supplemental zinc.

The UL, set by the Food and Nutrition Board, is based on the amount that would begin tointerfere with copper.

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 7Children 4-8 years 12

Children 9-13 years 23

Adolescents 14 18 years 34


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zinc and the antibiotic. Taking the antibiotic at least 2 hours before or 4–6 hours aftertaking a zinc supplement minimizes this interaction.

Penicillamine: Zinc can reduce the absorption and action of penicillamine, a drug used totreat rheumatoid arthritis.

Diuretics: Diuretics increase urinary zinc excretion by as much as 60% and, therefore,increases zinc excretion.

Zinc’s interconnectedness with other nutrients / nutrient-nutrient interactions45,46

Vitamin AZinc and vitamin A are connected in two rather significant ways:

1. Zinc is a component of retinol-binding protein (RBP). Recall this is necessary totransport vitamin A from the liver to target tissues in need. Therefore, during zincdeficiency, tissues in need of vitamin A do not receive it.

2. Zinc is required for the enzyme that converts retinol to retinal. Retinal is needed tocreate rhodopsin – the protein in the eye that absorbs light. Therefore, zinc

deficiency can contribute to night blindness.

Copper A high intake of zinc (50 mg/day or more over a period of weeks) can cause the creation ofmetallothionein within the intestine. Metallothionein interferes with copper bioavailability bytrapping copper in the intestinal cells and preventing if from being absorbed. The use ofzinc lozenges for up to 6-8 weeks can induce copper deficiency.

IronIron supplements (38-65 mg/day) can decrease zinc absorption, prompting some healthexperts to recommend zinc supplements for pregnant and lactating women taking moreth 60 /d f i H thi i t ti h t b f d t b th ith


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Quick-recap:

• Zinc and vitamin A: zinc is needed by RBP. Therefore, a lack of zinc = a lack ofvitamin A to tissues in need. Zinc is needed to convert retinol into retinal – retinal is

needed to create rhodopsin, the protein in the eye that absorbs light. Therefore, alack of zinc = potential for night blindness.

• Zinc and copper: high zinc = copper is trapped and not able to be absorbed =lowers levels of HDL.

• Zinc and iron: too much zinc can decrease iron absorption causing anemia. Toomuch iron can decrease zinc absorption.

• Zinc and calcium: calcium in combination with phytic acid reduces zinc absorption .

• Zinc and folic acid: folate bioavailability may go up when zinc is present.

• Zinc and protein: protein deficiency can cause zinc deficiency since zinc needs proteins to shuttle and store zinc in the body.

Absorption inhibitors / promoters47,48

Factors that affect the absorption of zinc include the body’s need for zinc and thecomposition of the meal in which zinc is consumed. Inhibitors of absorption include: fiber,phytates, oxalates, calcium, iron, and copper. Zinc competes with iron and copper for

absorption. Studies have found that up to a 50% decrease in zinc absorption occurs whencalcium supplements are taken with a meal. It should be noted, however, that althoughfoods high in phytates inhibit zinc absorption, a greater amount of zinc is absorbed whenthese food are fortified.

Enhancers of zinc absorption include: protein (amino acids cysteine and methionine),picolinic acids (from human milk), and low zinc stores.

Quick-recap: Absorption inhibitors: phytates, oxalates, fiber, calcium, iron, and copper. Absorption enhancers: phytases, protein, human milk, low zinc stores.

Stability49


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Zinc oxide tends to be the preferred choice due to its low cost and high stability over otherforms, which often tend to impact the taste of food and so are not frequently used.

Although a low extraction rate will result in reduced phytate content of cereals, it alsoreduces the zinc content. Therefore, the net effect on the zinc supply tends to be minimal.One strategy that works to increase the zinc content of low extraction flours is to activatephytases that are naturally present in most phytate-containing foods. How do you activatephytases? Germination, fermentation, and /or soaking. Therefore, a technique to increasezinc bioavailability includes soaking beans, grains, and seeds in water for several hoursbefore cooking and allowing them to sit after soaking until sprouts form. This allows for theactivation of phytates and the deactivation of phytates. The addition of animal sources can

also improve zinc absorption in high-phytate diets.

Quick-recap: Zinc oxide is the most common form of zinc used in fortification due to lowcost and high stability. Low extraction (i.e. highly processed foods) flours may allow for low

phytate but also cause a low zinc content. A good strategy to increase the zinc content oflow extraction flours: activate phytases by soaking or allowing to ferment / germinate. Theaddition of animal sources can also improve zinc absorption.


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Indicators / biomarkers of zinc deficiency53,54,55,56

Few reliable biomarkers for zinc deficiency exist to date. This is largely due to the fact that most tests used are not sensitiveenough to detect small changes in zinc status, require specialized equipment or expertise, or have readings that can beaffected by factors other than zinc status. For this reason, global prevalence of zinc deficiency is largely unknown. However,there is reason to believe zinc deficiency is common for the following reasons: 1) low plasma zinc, an indicator of severedepletion, has been demonstrated to be quite high in several population groups, and 2) several randomized control trialsamong stunted children and / or those with low plasma levels have demonstrated positive responses to zinc supplementation.

Indicator Cut-off to define deficiency Cons

Serum or plasma(most commonindicator)

25%, 2) HAZ forchildren under the age of five is > 20%, and 3) a high prevalence of diarrhea exists, although there is no designated cut-off at

53 Wardlaw, Hampl, DiSilvestro. 2004. Perspective in Nutrition. Sixth edition.

54 National Institutes of Health. Office of Dietary Supplements. http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

55 Allen L, de Benoist B, Dary O, Hurrell R. Guidelines on food fortification with micronutrients. WHO and FAO. 2006.

56 Food and Nutrition Bulletin. Volume 30. Number 1. March 2009.


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this point in time.

Quick-recap: Few reliable biomarkers for zinc deficiency exit to date. Serum or plasma zinc are the most common indicatorsused. A big downside is that plasma zinc is decreased by pregnancy, protein-energy malnutrition (PEM), and infection. Proxyindicators are used in lieu of a lack of reliable biomarkers: 1) prevalence of low serum zinc concentrations is > 20%, 2)

prevalence of inadequate intakes of zinc is > 25%, and 3) HAZ for children under the age of five is > 20%. A high prevalence ofdiarrhea is also often used as a proxy indictor, although there is no designated cut-off at this point in time.

2012 06 18 phc zinc final final

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