Calcium is found in several forms including calcium citrate and calcium gluconate. It is the most abundant mineral in the human body. While an average man contains about 1-1/2 kg of calcium, an average woman has about 1 kg, where 99 percent of that is in bones and teeth. The remaining 1 percent is located in the blood, lymph and other body fluids, cell membranes and structures inside cells.

Calcium participates in the metabolic functions necessary for normal activity of nervous, muscular, skeletal systems and plays an important role in normal heart function, kidney function, blood clotting, and blood-vessel integrity. Additionally, it helps to utilize vitamin B-12. It is available in both natural and synthetic sources, and some forms are only available by prescription.

How This Mineral Works in Your Body:

Note: With Complete H2O's ionic minerals, the human body absorbs the minerals much more easily at the cellular level in contrast to the food sources listed below. In addition, the chances of heavy metallic buildup within the cell structure is significantly reduced with Complete H2O's ionic minerals.

Almonds, Kelp, Kale, Brazil nuts, Milk, Broccoli, Pudding, Calcium-fortified Salmon, canned, Canned fish with bones, Cereal, rice, juice, Sardines, canned, Caviar, Tofu, Cheese, Turnip greens, Mustard greens, Cottage cheese, Yogurt, Figs, dried, Honeydew melon, Cauliflower, Walnuts, Peanuts, Baked beans, canned, Milk Chocolate, Soybeans, Crab meat, canned.

How to Use:

Take the recommended dosage of water soluable minerals with a full glass of water, juice or other liquid.

Daily recommended intakes:

Men 1000 mg

Pregnancy 1000 mg
(14-18) 1300 mg (14-18) 1300 mg
(over 55) 1200 mg Lactation 1000 mg
Women 1000 mg (14-18) 1300 mg
(14-18) 1300 mg
(over 55) 1200 mg

Cautions: Do not take if you have: Allergies to calcium or antacids High blood-calcium levels Sarcoidosis Consult your doctor if you have: Kidney disease Chronic constipation, colitis, diarrhea Stomach or intestinal bleeding Irregular heartbeat Heart problems or high blood pressure for which you are taking a calcium channel blocker

Over 55:

The likelihood of adverse reactions and side effects is greater Diarrhea or constipation are especially likely.


You may need extra calcium while pregnant. Speak with your physician about taking supplements. Do not take super doses.


The drug does pass into milk. Speak with your physician about taking supplements. DO not take super doses.


Keep in a cool and dry location and away from direct light, but do not freeze.

Keep safely away from children

Do not keep in bathroom medicine cabinet. Heat and dampness may alter the action of the mineral.

Safe dosage:

It is advised that you consult with your physician for the proper dose for your condition


Do not take calcium within 1 or 2 hours of meals or ingestion of other medications, if possible.

It is not recommended that you take calcium carbonate derived from oyster shells.

Dolomite and bone meal are probably not safe sources of calcium because they contain lead.

Symptoms of Deficiency:



Magnesium is one of the most plentiful minerals in the soft tissue. It is found in high concentrations inside cells, namely those of the brain and heart. The average adult body contains around 20-28 g of magnesium with about 60 percent is present in the bones. The rest is in the muscle, soft tissue and body fluids.

How This Mineral Works in Your Body:

With medical supervision, may supplement treatment of acute myocardial infarction, cardiac surgery, digitalis toxicity and congestive heart failure.

Where This Mineral is Found:

Note: With Complete H2O's ionic minerals, the human body absorbs the minerals much more easily at the cellular level in contrast to the food sources listed above. In addition, the chances of heavy metallic buildup within the cell structure is significantly reduced with Complete H2O's ionic minerals.

Almonds, Herring, Avocados, Leafy, green vegetables, Bananas, Mackerel, Bluefish, Molasses, Carp, Nuts, Cod, Ocean perch, Collards, beet greens, Shrimp, Dairy products, Swordfish, Flounder, Wheat germ, Halibut, Whole wheat bread, Peanuts, Baked beans, Beet greens, Brown rice, cooked, Kidney beans, can, Cashew nuts, Spinach, boiled, Halibut, baked, Chick peas, Black eyed peas, Artichokes, Apricots, dried, Sweetcorn, Green peas, Raisins,Whole wheat spaghetti, cooked, Avocado, Oatmeal, cooked.

How to Use:

Take the recommended dosage of water soluable minerals with a full glass of water, juice or other liquid.

Recommended Daily Intakes:

Suggested Intake: 350-500 mg

Men (under 30): 400 mg Lactating (14-18): 360 mg
Men (over 30): 420 mg Lactating (19-30): 310 mg
Women (under 30): 310 mg Lactating (over 30): 320 mg
Women (over 30): 320 mg Children(1-6 yrs): 80-130 mg
Pregnancy (14-18): 400 mg Children (9-13 yrs): 240 mg
Pregnancy (19-30): 350 mg Children (14-18yrs): 360-410 mg
Pregnancy (over 30): 360 mg


Do not take if you have:

Kidney failure, Heart block (unless you have a pacemaker), Had an ileostomy

Consult your doctor if you have: Chronic constipation, colitis, diarrhea Symptoms of appendicitis Stomach or intestinal bleeding

Over 55:

It is more likely that adverse reactions and side effects will be experienced Pregnancy: There is a risk to the fetus, therefore do not take. Breastfeeding: Do not take magnesium unless advised by your physician to do so.


Keep in a cool and dry location and away from direct light, but do not freeze.

Keep safely away from children

Do not keep in bathroom medicine cabinet. Heat and dampness may alter the action of the mineral.

Safe dosage:

It is advised that you consult with your physician for the proper dose for your condition


Excess magnesium is retained due to chronic kidney disease

Adverse reactions, side effects and interactions with medicines, vitamins or minerals occur only rarely when you take too much magnesium for too long or if you have kidney disease.

Symptoms of Deficiency:

Following symptoms occur rarely:



Silver originates from igneous rocks and sedimentary rocks and is found at the rate of 0.07ppm in rocks and in soils at the rate of 0. 1 ppm; fresh water at 0.000 13 ppm; sea water at 0.0003 ppm; marine algae at 0.25 ppm; land plants from 0.06 ppm to 1.4 ppm in accumulator plants growing near silver ore. Epiogonum ovalifolium is a silver indicator plant. Silver is found at 3.0 to 11.0 ppm in marine animals; in land mammals generally 0.05 to 0. 7 ppm; muscle at 0. 16 to 0.8 PPM and tortoise shell at 0.05 to 0.7ppm.

Silver has been employed in human health care and in the search for immortality since the days of the Chinese alchemist 8,000 years ago. Many feel that silver is in fact an essential element, not because it is required for an enzyme system, but rather as a systemic disinfectant and immune system support.

Sir Malcolm Morris reported in the British Medical Journal (May 12,1917) that water soluble silver is "free from the drawbacks of other preparations of silver, viz. pain caused and discoloration of the skin; indeed, instead of producing irritation it has a distinctly soothing effect. It rapidly subdues inflammation and promotes healing of the lesions, it can be used with remarkable results in enlarged prostate with irritation of the bladder, in pruritis ani and perineal eczema, and in hemorrhoids."

J.Mark Hovell reported in the British Medical Journal (December 15, 1917) that, "colloidal silver has been found to be beneficial for permanently restoring the patency of the Eustachian tubes and for reducing nasopharyngeal catarrh. Colloidal silver has also been used successfully in septic conditions of the mouth (including pyorrhea alveolysis - Rigg's disease), throat (including tonsillitis and quincies), ear (including Menier's symptoms and closure to Valsalva's inflation), and in generalized septicemia, leucorrhea, cystitis, whooping cough and shingles."

Taken internally, water-soluble silver is resistant to the action of dilute acids and alkalis of the stomach and intestine, and consequently continues their catalytic action and pass into the intestine unchanged.

T.H. Anderson Wells reported in Lancet (February 16, 1918) that a preparation of colloidal silver was "used intravenously in a case of puerperal septicemia without any irritation of the kidneys and with no pigmentation of the skin."

Silver sulfadiazine (Silvadene, Marion Laboratories) is used in 70 percent of the burn centers in America; discovered by Dr. Charles Fox, Columbia, University, sulfadiazine has been used successfully to treat syphilis, cholera and malaria; it also stops the herpes virus responsible for "coldsores" and "fever blisters."

Silver is an anti-bacterial, anti-viral, anti-fungal anti-metabolite that disables specific enzymes that microorganisms use for respiration. Silver is such an efficient anti-bactericidal that our "Great-grand mothers put silver dollars in fresh milk to keep it from spoiling at room temperature."

Humans can consume 400 mg of silver per day (as long as it is water-soluble). Silver "deficiency" results in an impaired immune system. In "The Body Electric", Robert Becker, M.D. identified a relationship between low levels of dietary silver and the rate of illness (flu, colds, etc.); he stated, "silver deficiency was responsible for the improper functioning of the immune system, and silver does more than just kill disease causing organisms; it was also causing major growth stimulation (another criteria for essentiality) of injured tissue." Human fibroblast cells were able to multiply at a great rate, producing large numbers of primitive, embryonic cells in wounds that are able to differentiate into whatever cell types that are necessary to heal the wound.

Dr. Bjorn Nordstrom, of the Karolinska Institute, Sweden, has used silver in his alternative cancer therapy programs.

According to Science Digest (Silver: Our Mightiest Germ Fighter. March 1978) silver is an antibiotic, silver kills over 650 disease causing organisms; resistant strains fail to develop; silver is absolutely non-toxic to humans at standard rates of consumption.

Even so, there is little evidence (from direct research) that silver is essential for any living organism, nor is it ranked among the more toxic trace elements. It occurs naturally in very low concentrations in soils, plants, and animal tissues, and can gain access to foods from silver-plated vessels, silver-lead solders, and silver foil used in decorating cakes and confectionary.

The fact that foods contain very little silver is supported by reports of nondetectable to less than a few nanograms of silver per gram of a variety of fruits and vegetables, and orange juice, the finding of only 10 ng silver per gram of fresh banana pulp, and the finding of 0.027 to 0.054 mg silver per liter (weighted average of 0.047 +or- 0.007 mg/liter) of cow's milk. Further support comes from the reported human dietary silver intakes of 27 ± 17 mcg/day (and <1.0 mcg/day.

The level of silver in normal human tissues is also very low. Hamilton et al. found the following mean values, expressed as micrograms of silver per gram fresh tissue: brain 0.004, kidneys 0.002, liver 0.006, lungs 0.002, lymph nodes 0.001, muscle 0.002, testis 0.002, and ovaries 0.002.


When uses of silver are mentioned here, I am talking about silver that is water-soluble; that is, silver ions only in distilled ozonated water. This solution is clear and non-toxic.

Applications include oral (as a gargle for sore throat or sores in the mouth), topical, and nasal, in the ear, vaginal or as a spray to other sensitive tissues. Silver kills all disease-causing bacteria, fungus, and viruses within a few minutes of application, but leaves the friendly microbes unharmed. Many use a silver solution daily or at least at regular intervals to boost their immune system. The silver solution does not sting, burn or hurt even the most sensitive of body tissues.

Silver can be used on warts, open sores or wounds, or a rinse for acne, eczema or other skin irritations. It can be used vaginally as a cleansing antiseptic douche, rectally as a cleansing enema, or atomized and inhaled. Silver in the water-soluble form has been used by my family as an antiseptic eye rinse.

Silver has been noted to kill over 650 microbial disease-causing organisms. This is like having a broad-spectrum antibiotic at you disposal. A few drops of silver solution can be put on a Band-Aid and worn over warts, scrapes or cuts. You can dab the silver solution directly on eczema or other itchy areas, on acne, mosquito bites or any skin problems. You can even put 3 or 4 ounces of silver into you your shampoo and use it as an antiseptic, dandruff shampoo. It can also be used as a rinse after shampooing.

Additionally, silver can be put into your water dispensers to keep not only the water sterile but also keeps the spout clean. There will be no slime in the spout or in the bottom of your dispenser here. Silver can sterilize drinking water and help keep milk fresh longer. (NOTE: The pioneers who traveled west would put silver coins in their water barrels to keep the water from spoiling). Use about 1 teaspoonful of silver per gallon of water. You can also use silver as a food preservative in canning at about 1/4 teaspoonful per quart.

Why haven't we heard of silver mineral water before?

Perhaps we have and do not remember. For many years all hospitals were required by law to use silver nitrate solution in the eyes of newborn babies. This was to insure the baby's eyesight if the mother had Gonorrhea. After application the tissue around the eyes would be stained black for a few days giving evidence of silver's use. This method was very inexpensive. But, not wanting to leave well enough alone, the hospitals abandoned its use when antibiotics became widely used. The "antiquated" silver solutions were quietly shelved in favor of the broad-spectrum antibiotics. So much for progress.



Potassium is found in several different forms, including Potassium Chloride—the most common form. It has many functions in the body such as playing a role in protein synthesis and for the conversion of blood sugar in to glycogen (sugar). It triggers a number of enzymes, namely those concerned with energy production. Potassium also stimulates normal movements of the intestinal tract. The average human body contains about 140 g of potassium.

How This Mineral Works in Your Body:

Potassium is the predominant positive electrolyte in body cells. An enzyme (adenosine triphosphatase) controls the flow of potassium and sodium into and out of cells to maintain normal function of the heart, brain, skeletal muscles and kidney, and to maintain acid-base balance.

Where This Mineral is Found:

Note: With Complete H2O's ionic minerals, the human body absorbs the minerals much more easily at the cellular level in contrast to the food sources listed above. In addition, the chances of heavy metallic buildup within the cell structure is significantly reduced with Complete H2O's ionic minerals.

Fruits, Vegetables, Whole grains, Asparagus, Molasses, Avocados, Nuts, Bananas, Parsnips, Beans, Peas (fresh), Cantaloupe, Potatoes, Carrots, Raisins, Chard, Salt substitute, Citrus fruit, Sardines, canned, Juices (grapefruit, tomato, orange), Spinach, fresh and boiled, Milk, Snapper, grilled, Prunes, Pistachios, Peanuts, Ham, Melon, Green peas, boiled, Barely, Beef.

How to Use:

Take the recommended dosage of water soluable minerals with a full glass of water, juice or other liquid.

Recommended Daily Intakes:

Suggested Intake: 2000-5000 mg

Men: 2000 mg

Women: 2000 mg


Do not take if you:

Take potassium-sparing diuretics, such as spironolactone, triamterene. or amiloride

Have allergies to any potassium supplement

Have kidney disease or are taking drugs which cause the kidney to retain potassium

Are dehydrated

Have heat cramps, ulcers

Consult your doctor if you have:

Over 55:

Carefully watch your dosage schedule; it is critical to maintain balance of potassium levels in the body. Deviation above or below normal levels can have serious implications.

There is a greater risk of hyperglycemia.


There are no problems expected, however consult your physician before use.


Studies on risks to infants is inconclusive. Consult your physician about taking supplements


Keep in a cool and dry location and away from direct light, but do not freeze.

Keep safely away from children

Do not keep in bathroom medicine cabinet. Heat and dampness may alter the action of the mineral.


Take with food.

Symptoms of Deficiency:



Copper (Cu) is an essential trace element for humans and animals. In the body, copper shifts between the cuprous (Cu1+) and the cupric (Cu2+) forms, though the majority of the body's copper is in the Cu2+ form. The ability of copper to easily accept and donate electrons explains its important role in oxidation-reduction (redox) reactions and the scavenging of free radicals. Although Hippocrates is said to have prescribed copper compounds to treat diseases as early as 400 B.C., scientists are still uncovering new information regarding the functions of copper in the human body.


Copper is a critical functional component of a number of essential enzymes, known as cuproenzymes. Some of the physiologic functions known to be copper-dependent are discussed below.

Energy production

The copper-dependent enzyme, cytochrome c oxidase, plays a critical role in cellular energy production. By catalyzing the reduction of molecular oxygen (O2) to water (H2O), cytochrome c oxidase generates an electrical gradient used by the mitochondria to create the vital energy-storing molecule, ATP.

Connective tissue formation

Another cuproenzyme, lysyl oxidase, is required for the cross-linking of collagen and elastin, which are essential for the formation of strong and flexible connective tissue. The action of lysyl oxidase helps maintain the integrity of connective tissue in the heart and blood vessels and plays a role in bone formation.

Iron metabolism

Two copper-containing enzymes, ceruloplasmin (ferroxidase I) and ferroxidase II have the capacity to oxidize ferrous iron (Fe2+) to ferric iron (Fe3+), the form of iron that can be loaded onto the protein transferrin for transport to the site of red blood cell formation. Although the ferroxidase activity of these two cuproenzymes has not yet been proven to be physiologically significant, the fact that iron mobilization from storage sites is impaired in copper deficiency supports their role in iron metabolism.

Central nervous system

A number of reactions essential to normal function of the brain and nervous system are catalyzed by cuproenzymes.

Neurotransmitter synthesis: Dopamine-b-monooxygenase catalyzes the conversion of dopamine to the neurotransmitter norepinephrine.

Metabolism of neurotransmitters: Monoamine oxidase (MAO) plays a role in the metabolism of the neurotransmitters norepinephrine, epinephrine, and dopamine. MAO also functions in the degradation of the neurotransmitter serotonin, which is the basis for the use of MAO inhibitors as antidepressants.

Formation and maintenance of myelin: The myelin sheath is made of phospholipids whose synthesis depends on cytochrome c oxidase activity.

Melanin formation

The cuproenzyme, tyrosinase, is required for the formation of the pigment melanin. Melanin is formed in cells called melanocytes and plays a role in the pigmentation of the hair, skin, and eyes.

Antioxidant functions

Superoxide dismutase: Superoxide dismutase (SOD) functions as an antioxidant by catalyzing the conversion of superoxide radicals (free radicals or ROS) to hydrogen peroxide, which can subsequently be reduced to water by other antioxidant enzymes. Two forms of SOD contain copper: 1) copper/zinc SOD is found within most cells of the body, including red blood cells, and 2) extracellular SOD is a copper containing enzyme found in high levels in the lungs and low levels in blood plasma.

Ceruloplasmin: Ceruloplasmin may function as an antioxidant in two different ways. Free copper and iron ions are powerful catalysts of free radical damage. By binding copper, ceruloplasmin prevents free copper ions from catalyzing oxidative damage. The ferroxidase activity of ceruloplasmin (oxidation of ferrous iron) facilitates iron loading onto its transport protein, transferrin, and may prevent free ferrous ions (Fe2+) from participating in harmful free radical generating reactions.

Regulation of gene expression

Copper-dependent transcription factors regulate transcription of specific genes. Thus, cellular copper levels may affect the synthesis of proteins by enhancing or inhibiting the transcription of specific genes. Genes regulated by copper-dependent transcription factors include genes for copper/zinc superoxide dismutase (Cu/Zn SOD), catalase (another antioxidant enzyme), and proteins related to the cellular storage of copper.

Nutrient-nutrient interactions

Iron: Adequate copper nutritional status appears to be necessary for normal iron metabolism and red blood cell formation. Anemia is a clinical sign of copper deficiency, and iron has been found to accumulate in the livers of copper deficient animals, indicating that copper (probably in the form of ceruloplasmin) is required for iron transport to the bone marrow for red blood cell formation (see Iron Metabolism). Infants fed a high iron formula absorbed less copper than infants fed a low iron formula, suggesting that high iron intakes may interfere with copper absorption in infants.

Zinc: High supplemental zinc intakes of 50 mg/day or more for extended periods of time may result in copper deficiency. High dietary zinc increases the synthesis of an intestinal cell protein called metallothionein, which binds certain metals and prevents their absorption by trapping them in intestinal cells. Metallothionein has a stronger affinity for copper than zinc, so high levels of metallothionein induced by excess zinc cause a decrease in intestinal copper absorption. High copper intakes have not been found to affect zinc nutritional status.

Fructose: High fructose diets have exacerbated copper deficiency in rats, but not in pigs whose gastrointestinal systems are more like those of humans. Very high levels of dietary fructose (20% of total calories) did not result in copper depletion in humans, suggesting that fructose intake does not result in copper depletion at levels relevant to normal diets.

Vitamin C: Although vitamin C supplements have produced copper deficiency in laboratory animals, the effect of vitamin C supplements on copper nutritional status in humans is less clear. Two small studies in healthy young adult men indicate that the oxidase activity of ceruloplasmin may be impaired by relatively high doses of supplemental vitamin C. In one study, vitamin C supplementation of 1,500 mg/day for 2 months resulted in a significant decline in ceruloplasmin oxidase activity. In the other study, supplements of 605 mg of vitamin C/day for 3 weeks resulted in decreased ceruloplasmin oxidase activity, although copper absorption did not decline. Neither of these studies found vitamin C supplementation to adversely affect copper nutritional status.


Clinically evident or frank copper deficiency is relatively uncommon. Serum copper levels and ceruloplasmin levels may fall to 30% of normal in cases of severe copper deficiency. One of the most common clinical signs of copper deficiency is an anemia that is unresponsive to iron therapy but corrected by copper supplementation. The anemia is thought to result from defective iron mobilization due to decreased ceruloplasmin activity. Copper deficiency may also result in abnormally low numbers of white blood cells known as neutrophils (neutropenia), a condition that may be accompanied by increased susceptibility to infection. Osteoporosis and other abnormalities of bone development related to copper deficiency are most common in copper-deficient low-birth weight infants and young children. Less common features of copper deficiency may include loss of pigmentation, neurological symptoms, and impaired growth.

Individuals at risk of deficiency

Cow's milk is relatively low in copper, and cases of copper deficiency have been reported in high-risk infants and children fed only cow's milk formula. High-risk individuals include: premature infants, especially those with low-birth weight, infants with prolonged diarrhea, infants and children recovering from malnutrition, individuals with malabsorption syndromes, including celiac disease, sprue, and short bowel syndrome due to surgical removal of a large portion of the intestine. Individuals receiving intravenous total parenteral nutrition or other restricted diets may also require supplementation with copper and other trace elements. Recent research indicates that cystic fibrosis patients may also be at increased risk of copper insufficiency.

How to Use:

Take the recommended dosage of water soluable minerals with a full glass of water, juice or other liquid.


Balanced Life

Our Balanced Life consists of a mixture of 8 ionic minerals: calcium, magnesium, potassium, sulfer, silicon, zinc, chloride and copper, then adds a balanced proprietary blend of essential micro-minerals.

The term vitamin is derived from the words vital and amine, because vitamins are required for life and were originally thought to be amines. Although not all vitamins are amines, they are organic compounds required by humans in small amounts from the diet. An organic compound is considered a vitamin if a lack of that compound in the diet results in overt symptoms of deficiency.

Minerals are elements that originate in the Earth and cannot be made by living systems. Plants obtain minerals from the soil, and most of the minerals in our diets come from directly from plants or indirectly from animal sources. Minerals may also be present in the water we drink, but this varies with geographic locale. Minerals from plant sources may also vary from place to place, because soil mineral content varies geographically.

How to Use:

Take the recommended dosage of water soluable minerals with a full glass of water, juice or other liquid.



Phytochemicals can be defined, in the strictest sense, as chemicals produced by plants. However, the term is generally used to describe chemicals from plants that may affect health, but are not essential nutrients. While there is ample evidence to support the health benefits of diets rich in fruits, vegetables, legumes, whole grains and nuts, evidence that these effects are due to specific nutrients or phytochemicals is very limited. Because plant-based foods are complex mixtures of bioactive compounds, information on the potential health effects of individual phytochemicals will be linked to information on the health effects of the foods that contain those phytochemicals.

How to Use:

Take the recommended dosage of water soluable minerals with a full glass of water, juice or other liquid.



Molybdenum is an essential trace element for virtually all life forms. It functions as a cofactor for a number of enzymes that catalyze important chemical transformations in the global carbon, nitrogen, and sulfur cycles. Thus, molybdenum-dependent enzymes are not only required for the health of the Earth's people, but for the health of its ecosystems as well.


The biological form of molybdenum present in almost all molybdenum-containing enzymes (molybdoenzymes) is an organic molecule known as the molybdenum cofactor. In humans, molybdenum is known to function as a cofactor for three enzymes. Sulfite oxidase catalyzes the transformation of sulfite to sulfate, a reaction that is necessary for the metabolism of sulfur-containing amino acids, such as cysteine. Xanthine oxidase and aldehyde oxidase catalyze hydroxylation reactions involving a number of different molecules with similar structures. Xanthine oxidase catalyzes the breakdown of nucleotides (precursors to DNA and RNA) to form uric acid, which contributes to the antioxidant capacity of the blood. Xanthine oxidase and aldehyde oxidase also play a role in the metabolism of drugs and toxins. Of these three enzymes, only sulfite oxidase is known to be crucial for human health.

Nutrient Interactions

Copper: Excess dietary molybdenum has been found to result in copper deficiency in grazing animals (ruminants). In ruminants, the formation of compounds containing sulfur and molybdenum, known as thiomolybdates, appears to prevent the absorption of copper. This interaction between thiomolybdates and copper does not occur to a significant degree in humans. One early study reported that molybdenum intakes of 500 and 1,500 mcg/day from sorghum increased urinary copper excretion. However, the results of a more recent and well-controlled study of molybdenum intake and copper metabolism in 8 healthy young men indicated that very high dietary molybdenum intakes (up to 1,500 mcg/day) did not adversely affect copper nutritional status.


Dietary molybdenum deficiency has never been observed in healthy people. The only documented case of acquired molybdenum deficiency occurred in a patient with Crohn's disease on long-term total parenteral nutrition (TPN) without molybdenum added to the TPN solution. The patient developed rapid heart and respiratory rates, headache, night blindness, and ultimately became comatose. He also demonstrated biochemical signs of molybdenum deficiency, including low plasma uric acid levels, decreased urinary excretion of uric acid and sulfate, and increased urinary excretion of sulfite. The symptoms disappeared when the administration of amino acid solutions was discontinued. Molybdenum supplementation (160 mcg/day) reversed the amino acid intolerance and improved his clinical condition.

Current understanding of the essentiality of molybdenum in humans is based largely on the study of individuals with very rare inborn errors of metabolism that result in a deficiency of the molybdoenzyme, sulfite oxidase. Two forms of sulfite oxidase deficiency have been identified: 1) isolated sulfite oxidase deficiency, in which only sulfite oxidase activity is affected and 2) molybdenum cofactor deficiency, in which the activity of all three molybdoenzymes is affected. Because molybdenum functions only in the form of the molybdenum cofactor in humans, any disturbance of molybdenum cofactor metabolism can disrupt the function of all molybdoenzymes. Together, molybdenum cofactor deficiency and isolated sulfite oxidase deficiency have been diagnosed in more than 100 individuals worldwide. Both disorders result from recessive traits, meaning that only individuals who inherit two copies of the abnormal gene (one from each parent) develop the disease. Individuals who inherit only one copy of the abnormal gene are known as carriers of the trait but do not exhibit any symptoms. The symptoms of isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are identical and usually include severe brain damage, which appears to be due to the loss of sulfite oxidase activity. At present, it is not clear whether the neurologic effects are a result of the accumulation of a toxic metabolite, such as sulfite, or inadequate sulfate production. Isolated sulfite oxidase deficiency and molybdenum cofactor deficiency can be diagnosed relatively early in pregnancy (10-14 weeks of gestation) through chorionic villus sampling, and in some cases, carriers of molybdenum cofactor deficiency can be identified through genetic testing. No cure is presently available for either disorder, although anti-seizure medications and dietary restriction of sulfur-containing amino acids may be beneficial in some cases.

The Recommended Dietary Allowance (RDA)

The recommended dietary allowance (RDA) for molybdenum was most recently revised in January 2001. It was based on the results of nutritional balance studies conducted in eight healthy young men under controlled laboratory conditions. The RDA values for molybdenum are listed in the table below in micrograms (mcg)/day by age and gender.

Recommended Dietary Allowance (RDA) for Molybdenum

Life Stage Age Males (mcg/day) Females (mcg/day)
Infants 0-6 months 2 (AI) 2 (AI)
Infants 7-12 months 3 (AI) 3 (AI)
Children 1-3 years 17 17
Children 4-8 years 22 22
Children 9-13 years 34 34
Adolescents 14-18 years 43 43
Adults 19 years and older 45 45
Pregnancy all ages 50
Breastfeeding all ages 50


Gastroesophageal cancer

Linxian is a small region in northern China where the incidence of cancer of the esophagus and stomach is very high (10 times higher than the average in China and 100 times higher than the average in the U.S.). The soil in this region is low in molybdenum and other mineral elements, so dietary molybdenum is also low. Increased intake of nitrosamines, which are known carcinogens, may be one of a number of dietary and environmental factors that contributes to the development of gastroesophageal cancer in this population. Plants require molybdenum to synthesize nitrate reductase, a molybdoenzyme necessary for converting nitrates from the soil to amino acids. When soil molybdenum content is low, plant conversion of nitrates to nitrosamines increases, resulting in increased nitrosamine exposure for those who consume the plants. Adding molybdenum to the soil in the form of ammonium molybdenate may help decrease the risk of gastroesophageal cancer by limiting nitrosamine exposure. It is not clear whether dietary molybdenum supplementation is beneficial in decreasing the risk of gastroesophageal cancer. In a large intervention trial, dietary supplementation of molybdenum (30 mcg/day) and vitamin C (120 mg/day) did not decrease the incidence of gastroesophageal cancer or other cancers in residents of Linxian over a five-year period.


Food sources

The Total Diet Study, an annual survey of the mineral content of representative diets of Americans, indicates that the dietary intake of molybdenum averages 76 mcg/day for women and 109 mcg/day for men. Thus, usual molybdenum intakes are well above the RDA for molybdenum. Legumes, such as beans, lentils, and peas, are the richest sources of molybdenum. Grain products and nuts are considered good sources, while animal products, fruits, and many vegetables are generally low in molybdenum. Because the molybdenum content of plants depends on the soil molybdenum content and environmental conditions, the molybdenum content of foods can vary considerably.


Molybdenum in nutritional supplements is generally in the form of sodium molybdate or ammonium molybdate.



The toxicity of molybdenum compounds appears to be relatively low in humans. Increased blood uric acid levels and gout-like symptoms have been reported in occupationally exposed workers in a copper-molybdenum plant and an Armenian population consuming 10 to 15 milligrams (mg) of molybdenum from food daily. In other studies, blood and urinary uric acid levels were not elevated by molybdenum intakes of up to 1.5 mg/day. There is one report of an acute toxic reaction associated with molybdenum from a dietary supplement. An adult male, reported to have consumed a total of 13.5 mg of molybdenum over a period of 18 days (300-800 mcg/day), developed acute psychosis with hallucinations, seizures, and other neurologic symptoms. However, a controlled study found no serious adverse effects of molybdenum intakes of up to 1.5 mg/day (1,500 mcg/day) for 24 days in four healthy young men.

The Food and Nutrition Board (FNB) of the Institute of Medicine found little evidence that molybdenum excess was associated with adverse health outcomes in generally healthy people. To determine the tolerable upper level of intake, the FNB selected adverse reproductive effects in rats as the most sensitive index of toxicity and applied a large uncertainty factor because animal data was used. Tolerable upper intake levels (UL) for molybdenum are listed by age group in the table below.

Tolerable Upper Intake Level (UL) for Molybdenum

Age Group UL (mcg/day)
Infants 0-12 months Not possible to establish*
Children 1-3 years 300
Children 4-8 years 600
Children 9-13 years 1,100 (1.1 mg/day)
Adolescents 14-18 years 1,700 (1.7 mg/day)
Adults 19 years and older 2,000 (2.0 mg/day)
*Source of intake should be from food and formula only.

Drug Interactions

High doses of molybdenum have been found to inhibit the metabolism of acetaminophen in rats. However, it is not known whether this occurs at clinically relevant doses in humans.


The RDA for molybdenum (45 mcg/day for adults) is sufficient to prevent deficiency. Although the intake of molybdenum most likely to promote optimum health is not known, there is presently no evidence that intakes higher than the RDA are beneficial. Most people in the U.S. consume more than sufficient molybdenum in their diets, making supplementation unnecessary. Following the Linus Pauling Institute's general recommendation to take a multivitamin/multimineral supplement that contains 100% of the daily values (DV) for most nutrients is likely to provide 75 mcg/day of molybdenum because the DV for molybdenum has not been revised to reflect the most recent RDA. Although the amount of molybdenum presently found in most multivitamin/mineral supplements is higher than the RDA, it is well below the tolerable upper intake level (UL) of 2,000 mcg/day and should be safe for adults.

Adults over the age of 65

Because aging has not been associated with significant changes in the requirement for molybdenum, our recommendation for molybdenum is the same for older adults.



Selenium is a trace element that is essential in small amounts, but can be toxic in larger amounts. Humans and animals require selenium for the function of a number of selenium-dependent enzymes, also known as selenoproteins. During selenoprotein synthesis, selenocysteine is incorporated into a very specific location in the amino acid sequence in order to form a functional protein. Unlike animals, plants do not appear to require selenium for survival. However, when selenium is present in the soil, plants incorporate it non-specifically into compounds that usually contain sulfur.



At least 11 selenoproteins have been characterized, and there is evidence that additional selenoproteins exist.

Glutathione peroxidases

Four selenium-containing glutathione peroxidases (GPx) have been identified: cellular or classical GPx, plasma or extracellular GPx, phospholipid hydroperoxide GPx, and gastrointestinal GPx. Although each GPx is a distinct selenoprotein, they are all antioxidant enzymes that reduce potentially damaging reactive oxygen species (ROS), such as hydrogen peroxide and lipid hydroperoxides, to harmless products like water and alcohols by coupling their reduction with the oxidation of glutathione (diagram). Sperm mitochondrial capsule selenoprotein, an antioxidant enzyme that protects developing sperm from oxidative damage and later forms a structural protein required by mature sperm, was once thought to be a distinct selenoprotein, but now appears to be phospholipid hydroperoxide GPx.

Thioredoxin reductase

In conjunction with the compound thioredoxin, thioredoxin reductase participates in the regeneration of several antioxidant systems, possibly including vitamin C. Maintenance of thioredoxin in a reduced form by thioredoxin reductase is important for regulating cell growth and viability.

Iodothyronine deiodinases (thyroid hormone deiodinases)

The thyroid gland releases very small amounts of biologically active thyroid hormone (triiodothyronine or T3) and larger amounts of an inactive form of thyroid hormone (thyroxine or T4) into the circulation. Most of the biologically active T3 in the circulation and inside cells is created by the removal of one iodine atom from T4 in a reaction catalyzed by selenium-dependent iodothyronine deiodinase enzymes. Through their actions on T3, T4, and other thyroid hormone metabolites, three different selenium-dependent iodothyronine deiodinases (types I, II, and III) can both activate and inactivate thyroid hormone, making selenium an essential element for normal development, growth, and metabolism through the regulation of thyroid hormones.

Selenoprotein P

Selenoprotein P is found in plasma and also associated with vascular endothelial cells (cells that line the inner walls of blood vessels). Although the function of selenoprotein P has not been clearly delineated, it has been suggested to function as a transport protein, as well as an antioxidant capable of protecting endothelial cells from damage by a reactive nitrogen species (RNS) called peroxynitrite.

Selenoprotein W

Selenoprotein W is found in muscle. Although its function is presently unknown, it is thought to play a role in muscle metabolism.

Selenophosphate synthetase

Incorporation of selenocysteine into selenoproteins is directed by the genetic code and requires the enzyme selenophosphate synthetase. A selenoprotein itself, selenophosphate synthetase catalyzes the synthesis of monoselenium phosphate, a precursor of selenocysteine which is required for the synthesis of selenoproteins.

Nutrient interactions

Antioxidant nutrients

As an integral part of the glutathione peroxidases and thioredoxin reductase, selenium probably interacts with every nutrient that affects the pro-oxidant/antioxidant balance of the cell. Other minerals that are critical components of antioxidant enzymes include copper, zinc (as superoxide dismutase), and iron (as catalase). Selenium as gluthathione peroxidase also appears to support the activity of vitamin E (a-tocopherol) in limiting the oxidation of lipids. Animal studies indicate that selenium and vitamin E tend to spare one another and that selenium can prevent some of the damage resulting from vitamin E deficiency in models of oxidative stress. Thioredoxin reductase also maintains the antioxidant function of vitamin C by catalyzing its regeneration.


Selenium deficiency may exacerbate the effects of iodine deficiency. Iodine is essential for the synthesis of thyroid hormone, but the selenoenzymes, iodothyronine deiodinases, are also required for the conversion of thyroxine (T4) to the biologically active thyroid hormone triiodothyronine (T3). Selenium supplementation in a small group of elderly individuals decreased plasma T4, indicating increased deiodinase activity with increased conversion to T3.


Insufficient selenium intake results in decreased activity of the glutathione peroxidases. Even when severe, isolated selenium deficiency does not usually result in obvious clinical illness. However, selenium deficient individuals appear to be more susceptible to additional physiological stresses.

Individuals at increased risk of selenium deficiency

Clinical selenium deficiency has been observed in chronically ill patients who were receiving total parenteral nutrition (TPN) without added selenium for prolonged periods of time. Muscular weakness, muscle wasting, and cardiomyopathy (inflammation and damage to the heart muscle) have been observed in these patients. TPN solutions are now supplemented with selenium to prevent such problems. People who have had a large portion of the small intestine surgically removed or those with severe gastrointestinal problems, such as Crohn's disease, are also at risk for selenium deficiency due to impaired absorption. Specialized medical diets used to treat metabolic disorders, such as phenylketonuria (PKU), are often low in selenium. Specialized diets that will be used exclusively over long periods of time should have their selenium content assessed to determine the need for selenium supplementation.

Keshan disease

Keshan disease is a cardiomyopathy that affects young women and children in a selenium deficient region of China. The acute form of the disease is characterized by the sudden onset of cardiac insufficiency, while the chronic form results in moderate to severe heart enlargement with varying degrees of cardiac insufficiency. The incidence of Keshan disease is closely associated with very low dietary intakes of selenium and poor selenium nutritional status. Selenium supplementation has been found to protect people from developing Keshan disease but cannot reverse heart muscle damage once it occurs. Despite the strong evidence that selenium deficiency is a fundamental factor in the etiology of Keshan's disease, the seasonal and annual variation in its occurrence suggests that an infectious agent is involved in addition to selenium deficiency. Coxsackievirus is one of the viruses that has been isolated from Keshan patients, and this virus has been found to be capable of causing an inflammation of the heart called myocarditis in selenium deficient mice. Studies in mice indicate that oxidative stress induced by selenium deficiency results in changes in the viral genome capable of converting a relatively harmless viral strain to a myocarditis-causing strain. Though not proven in Keshan disease, selenium deficiency may result in a more virulent strain of virus with the potential to invade and damage the heart muscle. See Disease Prevention for more information on selenium and viral infection.

Kashin-Beck Disease

Kashin-Beck disease is characterized by the degeneration of the articular cartilage between joints (osteoarthritis) and is associated with poor selenium status in areas of northern China, North Korea, and eastern Siberia. The disease affects children between the ages 5 and 13 years. Severe forms of the disease may result in joint deformities and dwarfism, due to degeneration of cartilage forming cells. Unlike Keshan disease, there is little evidence that improving selenium nutritional status prevents Kashin-Beck disease. Thus, the role of selenium deficiency in the etiology of Kashin-Beck disease is less certain. A number of other causative factors have been suggested for Kashin-Beck disease, including fungal toxins in grain, iodine deficiency, and contaminated drinking water.

The Recommended Dietary Allowance (RDA)

The RDA was revised in 2000 by the Food and Nutrition Board (FNB) of the Institute of Medicine. The most recent RDA is based on the amount of dietary selenium required to maximize the activity of the antioxidant enzyme glutathione peroxidase in blood plasma.

Recommended Dietary Allowance (RDA) for Selenium

Life Stage Age Males (mcg/day) Females (mcg/day)
Infants 0-6 months 15 (AI) 15 (AI)
Infants 7-12 months 20 (AI) 20 (AI)
Children 1-3 years 20 20
Children 4-8 years 30 30
Children 9-13 years 40 40
Adolescents 14-18 years 55 55
Adults 19 years and older 55 55
Pregnancy all ages 60
Breastfeeding all ages 70


Immune function

Selenium deficiency has been associated with impaired function of the immune system. Moreover, selenium supplementation in individuals who are not overtly selenium deficient appears to stimulate the immune response. In two small studies, healthy and immunosuppressed individuals supplemented with 200 mcg/day of selenium as sodium selenite for 8 weeks showed an enhanced immune cell response to foreign antigens compared with those taking a placebo. A considerable amount of basic research also indicates that selenium plays a role in regulating the expression of cell signaling molecules called cytokines, which orchestrate the immune response.

Viral infection

Selenium deficiency appears to enhance the virulence or progression of some viral infections. The increased oxidative stress resulting from selenium deficiency may induce mutations or changes in the expression of some viral genes. When selenium deficient mice are inoculated with a relatively harmless strain of coxsackievirus, mutations occur in the viral genome that result in a more virulent form of the virus, which causes an inflammation of the heart muscle known as myocarditis. Once mutated, this form of the virus also causes myocarditis in mice that are not selenium deficient, demonstrating that the increased virulence is due to a change in the virus rather than the effects of selenium deficiency on the host immune system. Recently, a study in mice that lack the cellular glutathione peroxidase enzyme (GPx-1 knockout mice) demonstrated that cellular glutathione peroxidase provides protection against myocarditis resulting from mutations in the genome of a previously benign virus. Selenium deficiency results in decreased activity of glutathione peroxidase, increasing the likelihood of mutations in the viral genome induced by oxidative damage. Coxsackievirus has been isolated from the blood of some sufferers of Keshan disease, suggesting that it may be a cofactor in the development of this cardiomyopathy associated with selenium deficiency in humans.


Animal studies

There is a great deal of evidence indicating that selenium supplementation at high levels reduces the incidence of cancer in animals. More than two-thirds of over 100 published studies in 20 different animal models of spontaneous, viral, and chemically induced cancers found that selenium supplementation significantly reduced tumor incidence. The evidence indicates that the methylated forms of selenium are the active species against tumors, and these methylated selenium compounds are produced at the greatest amounts with excess selenium intakes. Selenium deficiency does not appear to make animals more susceptible to developing cancerous tumors.

Epidemiological studies

Geographic studies have consistently shown a trend for populations who live in areas with low soil selenium and have relatively low selenium intakes to have higher cancer mortality rates. Results of epidemiological studies of cancer incidence in groups with less variable selenium intakes have been less consistent, but also show a trend for individuals with lower selenium levels (blood and nails) to have a higher incidence of several different types of cancer. However, this trend is less pronounced in women. For example, a prospective study of more than 60,000 female nurses in the U.S. found no association between toenail selenium levels and total cancer risk. Chronic infection with viral hepatitis B or C significantly increases the risk of liver cancer. In a study of Taiwanese men with chronic viral hepatitis B or C infection, decreased plasma selenium concentrations were associated with an even greater risk of liver cancer. A case-control study within a prospective study of over 9,000 Finnish men and women examined serum selenium levels in 95 individuals subsequently diagnosed with lung cancer and 190 matched controls. Lower serum selenium levels were associated with an increased risk of lung cancer and the association was more pronounced in smokers. In this Finnish population, selenium levels were only about 60% of selenium levels common in generally observed in other western countries. Another case-control study within a prospective study of over 50,000 male health professionals in the U.S. found a significant inverse relationship between toenail selenium content and the risk prostate cancer in 181 men diagnosed with advanced prostate cancer and 181 matched controls. In individuals whose toenail selenium content was consistent with an average intake of 159 mcg/day the risk of advanced prostate cancer was only 35% of that of individuals with toenail selenium content consistent with an intake of 86 mcg/day. Within a prospective study of more than 9,000 Japanese-American men, a case-control study that examined 249 confirmed cases of prostate cancer and 249 matched controls found the risk of developing prostate cancer to be 50% less in men with serum selenium levels in the highest quartile compared those in the lowest quartile, while another case-control study found that men with prediagnostic plasma selenium levels in the lowest quartile were 4 to 5 times more likely to develop prostate cancer than those in the highest quartile. In contrast, one of the largest case-control studies to date found a significant inverse association between toenail selenium and the risk of colon cancer, but no associations between toenail selenium and the risk of breast cancer or prostate cancer.

Human intervention trials

Undernourished populations: An intervention trial undertaken among a general population of 130,471 individuals in five townships of Quidong, China, a high-risk area for viral hepatitis B infection and liver cancer, provided table salt enriched with sodium selenite to the population of one township (20,847 people), using the other four townships as controls. During an 8-year follow up period the average incidence of liver cancer was reduced by 35% in the selenium enriched population, while no reduction was found in the control populations. In a clinical trial in the same region, 226 individuals with evidence of chronic hepatitis B infection were supplemented with either 200 mcg of selenium in the form of a selenium-enriched yeast tablet or a placebo yeast tablet daily. During the four-year follow up period 7 out of 113 individuals on the placebo developed primary liver cancer, while none of the 113 subjects supplemented with selenium developed liver cancer.

Well-nourished populations: In the U.S., a double blind, placebo-controlled study of more than 1300 older adults with a history of nonmelanoma skin cancer found that supplementation with 200 mcg/day of selenium-enriched yeast for an average of 7.4 years was associated with a 51% decrease in prostate cancer incidence in men. The protective effect of selenium supplementation was greatest in those men with lower baseline plasma selenium and prostate-specific antigen (PSA) levels. Surprisingly, the most recent results from this study indicate that selenium supplementation increased the risk of one type of skin cancer (squamous cell carcinoma) by 25%. Although selenium supplementation shows promise for the prevention of prostate cancer, its effects on the risk for other types of cancer is unclear. In response to the need to confirm these findings, several large placebo-controlled trials designed to further investigate the role of selenium supplementation in prostate cancer prevention are presently under way.

Possible mechanisms

Several mechanisms have been proposed for the cancer prevention effects of selenium: 1) maximizing the activity of antioxidant selenoenzymes and improving antioxidant status, 2) improving immune system function, 3) affecting the metabolism of carcinogens, and 4) increasing the levels of selenium metabolites that inhibit tumor cell growth. A two-stage model has been proposed to explain the different anticarcinogenic activities of selenium at different doses. At nutritional or physiologic doses (~ 40-100 mcg/day in adults) selenium maximizes antioxidant selenoenzyme activity and probably enhances immune system function, and carcinogen metabolism. At supranutritional or pharmacologic levels (~ 200-300 mcg/day in adults) the formation of selenium metabolites, especially methylated forms of selenium, may also exert anticarcinogenic effects.

Cardiovascular diseases

Theoretically, optimizing selenoenzyme activity could decrease the risk of cardiovascular diseases by decreasing lipid peroxidation and influencing the metabolism of cell signaling molecules known as prostaglandins. However, prospective studies in humans have not demonstrated strong support for the cardioprotective effects of selenium. While one study found a significant increase in illness and death from cardiovascular disease in individuals with serum selenium levels below 45 mcg/liter compared to matched pairs above 45 mcg/liter, another study, using the same cutoff points for serum selenium, found a significant difference only in deaths from stroke (31). A study of middle aged and elderly Danish men found an increased risk of cardiovascular disease in men with serum selenium levels below 79 mcg/liter, but several other studies found no clear inverse association between selenium nutritional status and cardiovascular disease risk. In a multi-center study in Europe, toenail selenium levels and risk of myocardial infarction (heart attack) were only associated in the center where selenium levels were the lowest. While some epidemiological evidence suggests that low levels of selenium (lower than those commonly found in the U.S.) may increase the risk of cardiovascular diseases, definitive evidence regarding the role of selenium in preventing cardiovascular diseases will require controlled clinical trials.

Disease Treatment


There appears to be a unique interaction between selenium and the human immunodeficiency viruses (HIV) that cause acquired immunodeficiency syndrome (AIDS). Declining selenium levels in HIV-infected individuals are sensitive markers of disease progression and severity, even before malnutrition becomes a factor. Low levels of plasma selenium have also been associated with a significantly increased risk of death from HIV. Adequate selenium nutritional status may increase resistance to HIV infection by enhancing the function of important immune system cells known as T cells and modifying their production of intracellular messengers known as cytokines. In HIV infection, increased oxidative stress appears to favor viral replication, possibly by activating specific transcription pathways. As an integral component of glutathione peroxidase and thioredoxin reductase, selenium plays an important role in decreasing oxidative stress in HIV-infected cells and possibly suppressing the rate of HIV replication. Recent research indicates that HIV may be capable of incorporating host selenium into viral selenoproteins that have glutathione-peroxidase activity. Though the significance of these findings requires further clarification, they suggest that both the human immune system and the activity of the virus are affected by selenium nutritional status.

Only a few trials of selenium supplementation in HIV-infected individuals have been published. Two uncontrolled trials of selenium supplementation (one using 400 mcg/day of selenium-enriched yeast and the other 80 mcg/day of sodium selenite plus 25 mg/day of vitamin C) reported subjective improvement, but did not demonstrate any improvement in biological parameters related to AIDS progression. Another trial followed 15 HIV-infected patients supplemented with 100 mcg/day of sodium selenite and 22 unsupplemented patients for 1 year and found evidence of decreased oxidative stress and a significant decrease in a biological marker of immunologic activation and HIV progression in the selenium supplemented patients. However, there were no differences in CD4 T cell count (an important biological marker of the progress of HIV infection) or mortality between the supplemented and unsupplemented patients. At least two double-blind placebo-controlled trials of selenium supplementation in HIV-positive individuals are presently under way.


Food sources

The richest food sources of selenium are organ meats and seafood, followed by muscle meats. In general, there is wide variation in the selenium content of plants and grains because plants do not appear to require selenium. Thus, the incorporation of selenium into plant proteins is dependent only on soil selenium content. Brazil nuts grown in areas of Brazil with selenium-rich soil may provide more than 100 mcg of selenium in one nut, while those grown in selenium-poor soil may provide 10 times less. In the U.S., grains are a good source of selenium, but fruits and vegetables tend to be relatively poor sources of selenium. In general, drinking water is not a significant source of selenium in North America. The average dietary intake of adults in the U.S. has been found to range from about 80 to 110 mcg/day. Because of food distribution patterns in the U.S., people living in areas with low soil selenium avoid deficiency because they eat foods produced in areas with higher soil selenium. The table below lists some good food sources of selenium and their selenium content in micrograms (mcg). For more information on the nutrient content of foods you eat frequently, search the USDA food composition database.

Food Serving Selenium (mcg)
Brazil nuts (from selenium-rich soil) 1 ounce (6-8 kernels) 839*
Shrimp 3 ounces (10-12) 34
Crab meat 3 ounces 40
Salmon 3 ounces 40
Halibut 3 ounces 40
Noodles, enriched 1 cup, cooked 35
Rice, brown 1 cup, cooked 19
Chicken (light meat) 3 ounces 20
Pork 3 ounces 33
Beef 3 ounces 17
Whole wheat bread 2 slices 15
Milk 8 ounces (1 cup) 5
Walnuts, black 1 ounce, shelled 5

*Above the tolerable upper intake level (UL) of 400 mcg/day.


Selenium supplements are available in several forms. Sodium selenite and sodium selenate are inorganic forms of selenium. Selenate is almost completely absorbed, but a significant amount is excreted in the urine before it can be incorporated into proteins. Selenite is only about 50% absorbed, but is better retained than selenate, once absorbed. Selenomethionine, an organic form of selenium that occurs naturally in foods, is about 90% absorbed. Selenomethionine and selenium-enriched yeast, which mainly supplies selenomethionine, are also available as supplements. The consumer should be aware that some forms of selenium yeast on the market contain yeast plus mainly inorganic forms of selenium. Both inorganic and organic forms of selenium can be metabolized to selenocysteine by the body and incorporated into selenoenzymes. At present, it is not clear whether one form of selenium is preferable to another. Most of the animal studies showing reduced tumor incidence used sodium selenite, as did two human trials showing enhancement of immune cell function. However, the placebo-controlled trial in humans that demonstrated a reduction in the incidence of prostate cancer used selenium yeast, which supplied mainly selenomethionine.

Selenium-enriched vegetables

Selenium-enriched garlic and ramps (wild leeks) have been shown to reduce chemically induced tumors in rats. Selenium-enriched vegetables are of interest to scientists because some the forms of selenium they produce (e.g., methylated forms of selenium) may be more potent inhibitors of tumor formation than the forms currently available in supplements. For more information on The Anti-cancer Effect of Selenium-enriched Ramps, see Dr. Phillip D. Whanger's article in the fall/winter 1999 issue of the Linus Pauling Institute newsletter.



Although selenium is required for health, high doses can be toxic. Acute and fatal toxicities have occurred with accidental or suicidal ingestion of gram quantities of selenium. Clinically significant selenium toxicity was reported in 13 individuals after taking supplements that contained 27.3 milligrams (27,300 mcg) per tablet due to a manufacturing error. Chronic selenium toxicity (selenosis) may occur with smaller doses of selenium over long periods of time. The most frequently reported symptoms of selenosis are hair and nail brittleness and loss. Other symptoms may include gastrointestinal disturbances, skin rashes, a garlic breath odor, fatigue, irritability, and nervous system abnormalities. In an area of China with a high prevalence of selenosis, toxic effects occurred with increasing frequency when blood selenium concentrations reached a level corresponding to an intake of 850 mcg/day. The Food and Nutrition Board (FNB) recently set the tolerable upper level (UL) for selenium at 400 mcg/day in adults based on the prevention of hair and nail brittleness and loss and early signs of chronic selenium toxicity. The UL of 400 mcg/day for adults (see table below) includes selenium obtained from food, which averages about 100 mcg/day for adults in the U.S., as well as selenium from supplements For more information on the data used to set the recent RDA and UL for selenium, see The New Recommendations for Dietary Antioxidants: A Response and Position Statement by the Linus Pauling Institute in the spring/summer 2000 issue of the Linus Pauling Institute newsletter.

Tolerable Upper Intake Level (UL) for Selenium

Age Group UL (mcg/day)
Infants 0-6 months 45
Infants 6-12 months 60
Children 1-3 years 90
Children 4-8 years 150
Children 9-13 years 280
Adolescents 14-18 years 400
Adults 19 years and older 400

Drug Interactions

At present, few interactions between selenium and medications are known. The anticonvulsant medication, valproic acid, has been found to decrease plasma selenium levels. Supplemental sodium selenite has been found to decrease toxicity from the antibiotic nitrofurantoin and the herbicide paraquat in animals.

Antioxidant Supplements and HMG-CoA Reductase Inhibitors (Statins)

A 3-year randomized controlled trial in 160 patients with documented coronary heart disease (CHD) and low HDL levels found that a combination of simvastatin (Zocor) and niacin increased HDL2 levels, inhibited the progression of coronary artery stenosis (narrowing), and decreased the frequency of cardiovascular events, such as myocardial infarction (heart attack) and stroke. Surprisingly, when an antioxidant combination (1,000 mg vitamin C, 800 IU alpha-tocopherol, 100 mcg selenium, and 25 mg beta-carotene daily) was taken with the simvastatin-niacin combination, the protective effects were diminished. Although the individual contribution of selenium to this effect cannot be determined, these findings highlight the need for further research on potential interactions between antioxidant supplements and cholesterol-lowering agents, such as HMG-CoA reductase inhibitors (statins).


The average American diet is estimated to provide about 100 mcg/day of selenium, an amount that is well above the current RDA (55 mcg/day) and appears sufficient to maximize plasma and cellular glutathione peroxidase activity. Although the amount of selenium in multivitamin supplements varies considerably, they rarely provide more than the Daily Value (DV) of 70 mcg. Eating a varied diet and taking a daily multivitamin supplement should provide sufficient selenium for most people in the U.S.


The only controlled trial to examine the effect of selenium supplementation on cancer risk in a well-nourished population found that 200 mcg/day of supplemental selenium significantly decreased the risk of prostate cancer in men by 51%. However, the risk of one type of skin cancer was increased by 25%. Although mortality from prostate cancer is considerably higher than mortality from squamous cell cancer of the skin, these findings suggest that the overall effects of selenium supplementation on cancer risk are not yet clear enough to support a general recommendation for an extra selenium supplement. Men taking supplemental selenium in order to reduce the risk of prostate cancer should not exceed 200 mcg/day and should take precautions to reduce the risk of squamous cell carcinoma, such as using sunscreen and avoiding prolonged sun exposure.


Because there is no evidence that selenium supplementation decreases the risk of cancer in women who are not selenium deficient, there is no reason for women to take an extra selenium supplement.

Older adults (65 years and older)

Because aging has not been associated with significant changes in the requirement for selenium, the Linus Pauling Institute Recommendation for selenium is the same for older men and women



Although trivalent chromium is recognized as a nutritionally essential mineral, scientists are not yet certain exactly how it functions in the body. The two most common forms of chromium are trivalent chromium (III) and hexavalent chromium (VI). Chromium (III) is the principal form in foods, as well as the form utilized by the body. Chromium (VI) is derived from chromium (III) by heating at alkaline pH and is used as a source of chromium for industrial purposes. It is a strong irritant and is recognized as a carcinogen when inhaled. At low levels, chromium (VI) is readily reduced to chromium (III) by reducing substances in foods and the acidic environment of the stomach, which serve to prevent the ingestion of chromium (VI).


A biologically active form of chromium participates in glucose metabolism by enhancing the effects of insulin. Insulin is secreted by specialized cells in the pancreas in response to increased blood glucose levels, for example, after a meal. Insulin binds to insulin receptors on the surface of cells, activating those receptors and stimulating glucose uptake by cells. Through its interaction with insulin receptors, insulin provides cells with glucose for energy and prevents blood glucose levels from becoming elevated. In addition to its effects on carbohydrate (glucose) metabolism, insulin also influences the metabolism of fat and protein. A decreased response to insulin or decreased insulin sensitivity may result in impaired glucose tolerance or type 2 diabetes, also known as non-insulin dependent diabetes mellitus (NIDDM). Type 2 diabetes is characterized by elevated blood glucose levels and insulin resistance.

The precise structure of the biologically active form of chromium is not known. Recent research suggests that a low-molecular-weight chromium-binding substance (LMWCr) may enhance the response of the insulin receptor to insulin. The following is a proposed model for the effect of chromium on insulin action (diagram). First, the inactive form of the insulin receptor is converted to the active form by binding insulin. The binding of insulin by the insulin receptor stimulates the movement of chromium into the cell and results in binding of chromium to apoLMWCr, a form of the LMWCr that lacks chromium. Once it binds chromium the LMWCr binds to the insulin receptor and enhances its activity. The ability of the LMWCr to activate the insulin receptor is dependent on its chromium content. When insulin levels drop due to normalization of blood glucose levels, the LMWCr may be released from the cell in order to terminate its effects.

Nutrient interactions

Iron: Chromium competes for one of the binding sites on the iron transport protein, transferrin. However, supplementation of older men with 925 mcg of chromium/day for 12 weeks did not significantly affect measures of iron nutritional status. A study of younger men found an insignificant decrease in transferrin saturation with iron after supplementation of 200 mcg of chromium/day for 8 weeks, but no long-term studies have addressed this issue. Iron overload in hereditary hemochromatosis may interfere with chromium transport by competing for transferrin binding. This has led to the hypothesis that decreased chromium transport might contribute to the diabetes associated with hereditary hemochromatosis.

Vitamin C: Chromium uptake is enhanced in animals when given at the same time as vitamin C (1). In a study of three women, administration of 100 mg of vitamin C together with 1 mg of chromium resulted in higher plasma levels of chromium than 1 mg of chromium without vitamin C.

Carbohydrates: Diets high in simple sugars (e.g., sucrose), compared to diets high in complex carbohydrates (e.g., whole grains), increase urinary chromium excretion in adults. This effect may be related to increased insulin secretion in response to the consumption of simple sugars compared to complex carbohydrates.


Chromium deficiency was reported in three patients on long-term intravenous feeding who did not receive supplemental chromium in their intravenous solutions. These patients developed evidence of abnormal glucose utilization and increased insulin requirements that responded to chromium supplementation. Additionally, impaired glucose tolerance in malnourished infants responded to an oral dose of chromium chloride. Because chromium appears to enhance the action of insulin and chromium deficiency has resulted in impaired glucose tolerance, chromium insufficiency has been hypothesized to be a contributing factor to the development of Type 2 diabetes.

Several studies of male runners indicated that urinary chromium loss was increased by endurance exercise, suggesting that chromium needs may be greater in individuals who exercise regularly. In a more recent study, resistive exercise (weight lifting) was found to increase urinary excretion of chromium in older men. However, chromium absorption was also increased, leading to little or no net loss of chromium as a result of resistive exercise.

At present, research on the effects of inadequate chromium intake and risk factors for chromium insufficiency are limited by the lack of sensitive and accurate tests for determining chromium nutritional status.

The Adequate Intake (AI)

Because there was not enough information on chromium requirements to set a recommended dietary allowance (RDA), the Food and Nutrition Board set an adequate intake level (AI) based on the chromium content in normal diets.

Adequate Intake (AI) for Chromium

Life Stage Age Males (mcg/day) Females (mcg/day)
Infants 0-6 months 0.2 0.2
Infants 7-12 months 5.5 5.5
Children 1-3 years 11 11
Children 4-8 years 15 15
Children 9-13 years 25 21
Adolescents 14-18 years 35 24
Adults 19-50 years 35 25
Adults 51 years and older 30 20
Pregnancy 18 years and younger 29
Pregnancy 19 years and older 30
Breastfeeding 18 years and younger 44
Breastfeeding 19 years and older 45


Impaired glucose tolerance and type 2 (non-insulin dependent) diabetes

In 12 out of 15 controlled studies of people with impaired glucose tolerance, chromium supplementation was found to improve some measure of glucose utilization or to have beneficial effects on blood lipid profiles. Impaired glucose tolerance refers to a metabolic state between normal glucose regulation and overt diabetes. Generally, blood glucose levels are higher than normal, but lower than those accepted as diagnostic for diabetes. Impaired glucose tolerance is associated with increased risk for cardiovascular diseases but is not associated with the other classic complications of diabetes. About 25% to 30% of individuals with impaired glucose tolerance eventually develop type 2 diabetes. Generally, chromium supplementation at doses of about 200 mcg/day, in a variety of forms for two to three months were found to be beneficial. The reasons for the variation or lack of effect in some studies are not clear, but chromium depletion is not the only known cause of impaired glucose tolerance. Additionally, the lack of an accurate measure of chromium nutritional status prevents researchers from identifying those individuals who are most likely to benefit from chromium supplementation.

Cardiovascular diseases

Impaired glucose tolerance and type 2 diabetes are associated with adverse changes in lipid profiles and increased risk of cardiovascular diseases. Studies examining the effects of chromium supplementation on lipid profiles have been notable for their inconsistent results. While some studies have observed reductions in serum total cholesterol, LDL-cholesterol, and triglyceride levels or increases in HDL-cholesterol levels, others have observed no effect. Such inconsistent responses of lipid and lipoprotein levels to chromium supplementation may reflect differences in chromium nutritional status. It is possible that only those individuals with insufficient chromium will experience beneficial effects on lipid profiles due to chromium supplementation.

Health claims

Increases muscle mass: Claims that chromium supplementation increases lean body mass and decreases body fat are based on the relationship between chromium and insulin action (see Function). In addition to affecting glucose metabolism, insulin is known to affect fat and protein metabolism. At least 12 placebo-controlled studies have compared the effect of chromium supplementation (200-1,000 mcg as chromium picolinate/day) with or without an exercise program on lean body mass and measures of body fat. In general, those studies that have used the most sensitive and accurate methods of measuring body fat and lean mass (dual energy x-ray absorbtiometry or DEXA and hydrodensitometry or underwater weighing) do not indicate a beneficial effect of chromium supplementation on body composition.

Promotes weight loss: Controlled studies of chromium supplementation (200-400 mcg as chromium picolinate/day) have demonstrated little if any beneficial effect on weight or fat loss, and claims of weight loss in humans appear to be exaggerated. In 1997 the U.S. Federal Trade Commission (FTC) ruled that there is no basis for claims that chromium picolinate promotes weight loss and fat loss in humans.


Type 2 (non-insulin dependent) diabetes

Type 2 diabetes is characterized by elevated blood glucose levels and insulin resistance. Although insulin levels in type 2 diabetics may be higher than in healthy individuals, the physiological effects of insulin are reduced. Because chromium is known to enhance the action of insulin, the relationship between chromium nutritional status and type 2 diabetes has generated considerable scientific interest. Individuals with type 2 diabetes have been found to have higher rates of urinary chromium loss than healthy individuals, especially those with diabetes of more than 2 years duration. Prior to 1997, well-designed studies of chromium supplementation in individuals with type 2 diabetes showed no improvement in blood glucose control, though they provided some evidence of reduced insulin levels and improved blood lipid profiles. In 1997, the results of a placebo-controlled trial conducted in China indicated that chromium supplementation might be beneficial in the treatment of type 2 diabetes. One hundred eighty participants took either a placebo, 200 mcg/day, or 1,000 mcg/day of chromium in the form of chromium picolinate. At the end of four months, blood glucose levels were 15%-19% lower in those that took 1,000 mcg/day compared with those that took a placebo. Blood glucose levels in those that took 200 mcg/day did not differ significantly from those that took a placebo. Insulin levels were lower in those who took either 200 mcg/day or 1,000 mcg/day. Glycosylated hemoglobin levels, a measure of long-term control of blood glucose, were also lower in both chromium-supplemented groups, but they were lowest in the group taking 1,000 mcg/day. Because the chromium nutritional status of the Chinese participants was not evaluated, and the prevalence of obesity was much lower than is typically associated with type 2 diabetics in the U.S., extrapolation of these results to a U.S. population is difficult. However, the findings in the Chinese population emphasize the need for large-scale randomized controlled trials of chromium supplementation for type 2 diabetes in the U.S .

Gestational diabetes

Few studies have examined the effects of chromium supplementation on gestational diabetes. Gestational diabetes occurs in about 2% of pregnant women and usually appears in the second or third trimester of pregnancy. Blood glucose levels must be tightly controlled to prevent adverse effects on the developing fetus. After delivery, glucose tolerance generally reverts to normal. However, 30% to 40% of women who have had gestational diabetes develop type 2 diabetes within 5 to 10 years. An observational study in pregnant women did not find serum chromium levels to be associated with measures of glucose tolerance or insulin resistance in late pregnancy, although serum chromium levels may not reflect tissue chromium levels. Women with gestational diabetes whose diets were supplemented with 4 mcg of chromium per kilogram of body weight daily as chromium picolinate for 8 weeks had decreased fasting blood glucose and insulin levels compared with those who took a placebo. However, insulin therapy rather than chromium picolinate was required to normalize severely elevated blood glucose levels.


Food sources

The amount of chromium in foods is variable, and it has been measured accurately in relatively few foods. Presently, there is no large database for the chromium content of foods. Processed meats, whole grain products, ready-to-eat bran cereals, green beans, broccoli, and spices are relatively rich in chromium. Foods high in simple sugars, such as sucrose and fructose, are not only low in chromium but have been found to promote chromium loss. Estimated average chromium intakes in the U.S. range from 23-29 mcg/day for adult women and 39-54 mcg/day for adult men. The chromium content of some foods is listed below in micrograms (mcg). Because chromium content in different batches of the same food has been found to vary significantly, the information in the table below should serve only as a guide to the chromium content of foods.

Food Serving Chromium (mcg)
Broccoli 1/2 cup 11.0
Green beans 1/2 cup 1.1
Potatoes 1 cup, mashed 2.7
Grape juice 8 fl. ounces 7.5
Orange juice 8 fl. ounces 2.2
Beef 3 ounces 2.0
Turkey breast 3 ounces 1.7
Turkey ham (processed) 3 ounces 10.4
Waffle 1 (~2.5 ounces) 6.7
Bagel 1 2.5
English muffin 1 3.6
Apple w/ peel 1 medium 1.4
Banana 1 medium 1.0


Chromium (III) is available as a supplement in several forms: chromium chloride, chromium nicotinate, chromium picolinate, and high-chromium yeast. They are available as stand-alone supplements or in combination products. Doses typically range from 50 to 200 mcg of elemental chromium. Chromium nicotinate and chromium picolinate may be more bioavailable than chromium chloride. In much of the research on impaired glucose tolerance and type 2 diabetes, chromium picolinate was the source of chromium. However, some concerns have been raised over the long-term safety of chromium picolinate supplementation (see Safety).



Hexavalent chromium or chromium (VI) is a recognized carcinogen. Exposure to chromium (VI) in dust is associated with increased incidence of lung cancer and is known to cause inflammation of the skin (dermatitis). In contrast, there is little evidence that trivalent chromium or chromium (III) is toxic to humans. Because no adverse effects have been convincingly associated with excess intake of chromium (III) from food or supplements, the Food and Nutrition Board (FNB) of the Institute of Medicine did not set a tolerable upper level of intake (UL) for chromium. Because information is limited, the FNB acknowledged a potential for adverse effects of high intakes of supplemental chromium (III) and advised caution.

Most of the concerns regarding the long-term safety of chromium (III) supplementation arise from several studies in cell culture, suggesting chromium (III), especially in the form of chromium picolinate, may increase DNA damage. Presently, there is no evidence that chromium (III) increases DNA damage in living organisms, and a study in 10 women taking 400 mcg/day of chromium as chromium picolinate found no evidence of increased oxidative damage to DNA as measured by antibodies to an oxidized DNA base.

Several studies have demonstrated the safety of daily doses of up to 1,000 mcg of chromium for several months. However, there have been a few isolated reports of serious adverse reactions to chromium picolinate. Kidney failure was reported five months after a six-week course of 600 mcg of chromium/day in the form of chromium picolinate, while kidney failure and impaired liver function were reported after the use of 1,200-2,400 mcg/day of chromium in the form of chromium picolinate over a period of four to five months. Individuals with pre-existing kidney or liver disease may be at increased risk of adverse effects and should limit supplemental chromium intake.

Drug interactions

Little is known about drug interactions with chromium in humans. Large doses of calcium carbonate or magnesium hydroxide-containing antacids decreased chromium absorption in rats. Aspirin and indomethacin (a non-steroidal anti-inflammatory drug) increased chromium absorption in rats.


The lack of sensitive indicators of chromium nutritional status in humans makes it difficult to determine the level of chromium 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 60-120 mcg/day of chromium, well above the adequate intake level of 20 to 25 mcg/day for adult women and 30 to 35 mcg for adult men.

Adults over the age of 65

Although the requirement for chromium is not known to be higher for older adults, one study found that chromium concentrations in hair, sweat, and urine decreased with age. Following the Linus Pauling Institute recommendation to take a multivitamin/multimineral supplement containing 100% of the daily values (DV) of most nutrients should provide sufficient chromium for most older adults.

Because impaired glucose tolerance and type 2 diabetes are associated with potentially serious health problems, individuals considering high-dose chromium supplementation to treat either condition should do so in collaboration with a qualified health care provider.



Iodine, a non-metallic trace element, is required by humans for the synthesis of thyroid hormones. Iodine deficiency is an important health problem throughout much of the world. Most of the Earth's iodine is found in its oceans. In general, the older an exposed soil surface, the more likely the iodine has been leached away by erosion. Mountainous regions, such as the Himalayas, the Andes, and the Alps, and flooded river valleys, such as the Ganges, are among the most severely iodine deficient areas in the world.


Iodine is an essential component of the thyroid hormones, triiodothyronine (T3) and thyroxine (T4) and is therefore, essential for normal thyroid function. To meet the body's demand for thyroid hormones, the thyroid gland traps iodine from the blood and converts it into thyroid hormones that are stored and released into the circulation when needed. In target tissues, such as the liver and the brain, T3, the physiologically active thyroid hormone, can bind to thyroid receptors in the nuclei of cells and regulate gene expression. T4, the most abundant circulating thyroid hormone, can be converted to T3 by enzymes known as deiodinases in target tissues. In this manner, thyroid hormones regulate a number of physiologic processes, including growth, development, metabolism, and reproductive function.

The regulation of thyroid function is a complex process that involves the brain (hypothalamus) and pituitary gland. In response to thyrotropin-releasing hormone (TRH) secretion by the hypothalamus, the pituitary gland secretes thyroid-stimulating hormone (TSH), which stimulates iodine trapping, thyroid hormone synthesis, and release of T3 and T4 by the thyroid gland. The presence of adequate circulating T4 decreases the sensitivity of the pituitary gland to TRH, limiting its secretion of TSH (diagram). When circulating T4 levels decrease, the pituitary increases its secretion of TSH, resulting in increased iodine trapping, as well as increased production and release of T3 and T4. Iodine deficiency results in inadequate production of T4. In response to decreased blood levels of T4, the pituitary gland increases its output of TSH. Persistently elevated TSH levels may lead to hypertrophy (enlargement) of the thyroid gland, also known as goiter (see Deficiency).


Iodine deficiency is now accepted as the most common cause of preventable brain damage in the world. According to the World Health Organization (WHO), iodine deficiency disorders (IDD) affect 740 million people throughout the world, and nearly 50 million people suffer from some degree of IDD-related brain damage. The spectrum of IDD includes mental retardation, hypothyroidism, goiter, and varying degrees of other growth and developmental abnormalities. Nearly 2.2 million people throughout the world live in areas of iodine deficiency and risk its consequences. Major international efforts have produced dramatic improvements in the correction of iodine deficiency in the 1990's mainly through the use of iodized salt and iodized vegetable oil in iodine deficient countries. For more information on the international effort to eradicate iodine deficiency visit the Web sites of the International Council for Control of Iodine Deficiency Disorders (ICCIDD) or the WHO.

Thyroid enlargement, or goiter, is one of the earliest and most visible signs of iodine deficiency. The thyroid enlarges in response to persistent stimulation by TSH (see Function). In mild iodine deficiency, this adaptation response may be enough to provide the body with sufficient thyroid hormone. However, more severe cases of iodine deficiency result in hypothyroidism. Adequate iodine intake will generally reduce the size of goiters, but the reversibility of the effects of hypothyroidism depends on an individual's stage of development. Iodine deficiency has adverse effects in all stages of development, but is most damaging to the developing brain. In addition to regulating many aspects of growth and development, thyroid hormone is important for the myelination of the central nervous system, which is most active before and shortly after birth.

The effects of iodine deficiency by developmental stage

Prenatal development: Fetal iodine deficiency is caused by iodine deficiency in the mother. One of the most devastating effects of maternal iodine deficiency is congenital hypothyroidism, a condition that is sometimes referred to as cretinism and results in irreversible mental retardation. Congenital hypothyroidism occurs in two forms, although there is considerable overlap between them. The neurologic form is characterized by mental and physical retardation and deafness. It is the result of maternal iodine deficiency that affects the fetus before its own thyroid is functional. The myxedematous or hypothyroid form is characterized by short stature and mental retardation. In addition to iodine deficiency, the hypothyroid form has been associated with selenium deficiency (see Nutrient Interactions) and the presence of goitrogens in the diet that interfere with thyroid hormone production (see Goitrogens).

Newborns and infants: Infant mortality is increased in areas of iodine deficiency, and several studies have demonstrated an increase in childhood survival when iodine deficiency is corrected. Infancy is a period of rapid brain growth and development. Sufficient thyroid hormone, which depends on adequate iodine intake, is essential for normal brain development. Even in the absence of congenital hypothyroidism, iodine deficiency during infancy may result in abnormal brain development and, consequently, impaired intellectual development.

Children and adolescents: Iodine deficiency in children and adolescents is often associated with goiter. The incidence of goiter peaks in adolescence and is more common in girls. School children in iodine deficient areas show poorer school performance, lower IQs, and a higher incidence of learning disabilities than matched groups from iodine-sufficient areas. A recent meta-analysis of 18 studies concluded that iodine deficiency alone lowered mean IQ scores in children by 13.5 points.

Adults: Inadequate iodine intake may also result in goiter and hypothyroidism in adults. Although the effects of hypothyroidism are more subtle in the brains of adults than children, recent research suggests that hypothyroidism results in slower response times and impaired mental function.

Pregnancy and lactation: Iodine requirements are increased in pregnant and breastfeeding women (see The RDA). Iodine deficiency during pregnancy has been associated with increased incidence of miscarriage, stillbirth, and birth defects. Moreover, severe iodine deficiency during pregnancy may result in congenital hypothyroidism in the offspring (see Prenatal development). Iodine deficient women who are breastfeeding may not be able to provide sufficient iodine to their infants who are particularly vulnerable to the effects of iodine deficiency (see Newborns and infants). A daily prenatal supplement providing 150 mcg of iodine will help to ensure that pregnant and breastfeeding women consume sufficient iodine during these critical periods.

Because iodine deficiency results in increased iodine trapping by the thyroid, iodine deficient individuals of all ages are more susceptible to radiation-induced thyroid cancer (see Disease Prevention) as well as to iodine-induced hyperthyroidism (see Safety).

Nutrient Interactions

Selenium deficiency can exacerbate the effects of iodine deficiency. Iodine is essential for the synthesis of thyroid hormone, but selenium-dependent enzymes (iodothyronine deiodinases) are also required for the conversion of thyroxine (T4) to the biologically active thyroid hormone, triiodothyronine (T3). Deficiencies of vitamin A or iron may also exacerbate the effects of iodine deficiency.


Some foods contain substances that interfere with iodine utilization or thyroid hormone production, known as goitrogens. The occurrence of goiter in the Democratic Republic of Congo has been related to the consumption of casava, which contains a compound that is metabolized to thiocyanate and blocks thyroidal uptake of iodine. Some species of millet and cruciferous vegetables (for example, cabbage, broccoli, cauliflower, and Brussel sprouts) also contain goitrogens. The soybean isoflavones, genistein and daidzein, have also been found to inhibit thyroid hormone synthesis. Most of these goitrogens are not of clinical importance unless they are consumed in large amounts or there is coexisting iodine deficiency. Recent findings also indicate that tobacco smoking may be associated with an increased risk of goiter in iodine deficient areas.

Individuals at risk of iodine deficiency

While the risk of iodine deficiency for populations living in iodine-deficient areas without adequate iodine fortification programs is well recognized, concerns have been raised that certain subpopulations may not consume adequate iodine in countries considered iodine-sufficient. Vegetarian and nonvegetarian diets that exclude iodized salt, fish, and seaweed have been found to contain very little iodine. Urinary iodine excretion studies suggest that iodine intakes are declining in Switzerland, New Zealand, and the U.S., possibly due to increased adherence to dietary recommendations to reduce salt intake. Although iodine intake in the U.S. remains sufficient, further monitoring of iodine intake has been recommended.

The Recommended Dietary Allowance (RDA)

The RDA for iodine was reevaluated by the Food and Nutrition Board (FNB) of the Institute of Medicine in 2001. The recommended amounts were calculated using several methods, including the measurement of iodine accumulation in the thyroid glands of individuals with normal thyroid function. These recommendations are in agreement with those of the International Council for Control of Iodine Deficiency Disorders, the World Health Organization, and UNICEF.

Recommended Dietary Allowance (RDA) for Iodine

Life Stage Age Males (mcg/day) Females (mcg/day)
Infants 0-6 months 110 (AI) 110 (AI)
Infants 7-12 months 130 (AI) 130 (AI)
Children 1-3 years 90 90
Children 4-8 years 90 90
Children 9-13 years 120 120
Adolescents 14-18 years 150 150
Adults 19 years and older 150 150
Pregnancy all ages 220
Breastfeeding all ages 290


Radiation-induced thyroid cancer

Radioactive iodine, especially 131I may be released into the environment as a result of nuclear reactor accidents. Thyroid accumulation of radioactive iodine increases the risk of developing thyroid cancer, especially in children. The increased iodine trapping activity of the thyroid gland in iodine deficiency results in increased thyroid accumulation of radioactive iodine (131I). Thus, iodine deficient individuals are at increased risk of developing radiation-induced thyroid cancer because they will accumulate greater amounts of radioactive iodine. Potassium iodide administered in pharmacologic doses (50-100 mg for adults) within 48 hours before or 8 hours after radiation exposure from a nuclear reactor accident can significantly reduce thyroid uptake of 131I and decrease the risk of radiation-induced thyroid cancer. The prompt and widespread use of potassium iodide prophylaxis in Poland after the 1986 Chernobyl nuclear reactor accident may explain the lack of a significant increase in childhood thyroid cancer in Poland compared to fallout areas where potassium iodide prophylaxis was not widely used. In the U.S. the Nuclear Regulatory Commission (NRC) requires that consideration be given to including potassium iodide as a protective measure for the general public in the case of a major release of radioactivity from a nuclear power plant.


Fibrocystic breast condition

Fibrocystic breast condition: Fibrocystic breast condition is a benign (non-cancerous) condition of the breasts, characterized by lumpiness and discomfort in one or both breasts. In estrogen treated rats, iodine deficiency leads to changes similar to those seen in fibrocystic breast condition, while iodine repletion was found to reverse those changes. An uncontrolled study of 233 women with fibrocystic breast condition found that treatment with aqueous molecular iodine (I2) at a dose of 0.08 mg of I2/kg of body weight daily over 6 to 18 months was associated with improvement in pain and other symptoms in over 70% of those treated. About 10% of the study participants reported side effects that were described by the investigators as minor. A double blind, placebo-controlled trial of aqueous molecular iodine (0.07-0.09 mg of I2/kg of body weight daily for 6 months) in 56 women with fibrocystic breast condition found that 65% of the women taking molecular iodine reported improvement compared to 33% of those taking the placebo. Although the investigators recommended larger controlled clinical trials to determine the therapeutic value of molecular iodine in fibrocystic breast condition, no further results have been published in the scientific or medical literature. The doses of iodine used in these studies (about 5 mg for a 60 kg person) were several times higher than the tolerable upper level of intake (UL) recommended by the Food and Nutrition Board (FNB) of the Institute of Medicine and should only be used under medical supervision.


Food sources

Although data from the Total Diet Study indicate that the average iodine intake in the U.S. is 240-300 mcg/day for adult men and 190-210 mcg/day for adult women, iodine intake in the U.S. has decreased significantly over the past 20 years. Between 1988 and 1994, 11% of the U.S. population was found to have low urinary iodine concentrations, more than 4 times the proportion found between 1971 and 1974. Moreover, 6.7% of pregnant women and 14.5% of women of childbearing age had urinary iodine concentrations associated with insufficient iodine intake.

The iodine content of most foods depends on the iodine content of the soil in which it was raised. Seafood is rich in iodine because marine animals can concentrate the iodine from seawater. Certain types of seaweed (e.g. wakame) are also very rich in iodine. Processed foods may contain slightly higher levels of iodine due to the addition of iodized salt or food additives, such as calcium iodate and potassium iodate. Dairy products are relatively good sources of iodine because iodine is commonly added to animal feed in the U.S. In the U.K. and northern Europe, iodine levels in dairy products tend to be lower in summer when cattle are allowed to graze in pastures with low soil iodine content (5). The table below lists the iodine content of some iodine-rich foods in micrograms (mcg). Because the iodine content of foods can vary considerably, these values should be considered approximate.

Food Serving Iodine (mcg)
Salt (iodized) 1 gram 77
Cod 3 ounces* 99
Shrimp 3 ounces 35
Fish sticks 2 fish sticks 35
Tuna, canned in oil 3 ounces (1/2 can) 17
Milk (cow's) 1 cup (8 fluid ounces) 56
Egg, boiled 1 large 29
Navy beans, cooked 1/2 cup 35
Potato with peel, baked 1 medium 63
Turkey breast, baked 3 ounces 34
Seaweed 1 ounce, dried Variable may be greater than 18,000 mcg (18 mg)
*A three-ounce serving of meat is about the size of a deck of cards.


Potassium iodide is available as a nutritional supplement, typically in combination products, such as multivitamin/multimineral supplements. Iodine makes up approximately 77% of the total weight of potassium iodide. A multivitamin/multimineral supplement that contains 100% of the daily value (DV) for iodine provides 150 mcg of iodine. Although most people in the U.S. consume sufficient iodine in their diets from iodized salt and food additives, an additional 150 mcg/day is unlikely to result in excessive iodine intake (see Safety).

Potassium iodide as well as potassium iodate may be used to iodize salt. In the U.S. and Canada, iodized salt contains 77 mcg of iodine per gram of salt. A more common recommendation for salt iodization is 20-40 mcg/gram depending on variables such as iodine intake from other sources and daily salt consumption. Iodized vegetable oil is also used in some countries as an iodine source.


Acute toxicity

Acute iodine poisoning is rare and usually occurs only with doses of many grams. Symptoms of acute iodine poisoning include burning of the mouth, throat, and stomach, fever, nausea, vomiting, diarrhea, a weak pulse, and coma.

Iodine excess

It is rare for diets of natural foods to supply more than 2,000 mcg of iodine/day, and most diets supply less than 1,000 mcg/day. People living in the northern coastal regions of Japan, whose diets contain large amounts of seaweed, have been found to have iodine intakes ranging from 50,000 to 80,000 mcg (50-80 mg) of iodine/day.

In iodine deficiency: Iodine supplementation programs in iodine-deficient populations have been associated with an increased incidence of iodine-induced hyperthyroidism (IHH), mainly in older people and those with multinodular goiter. Iodine intakes of 150-200 mcg/day have been found to increase the incidence of IHH in iodine-deficient populations. Iodine deficiency increases the risk of developing autonomous thyroid nodules that are unresponsive to the normal thyroid regulation system (see Function), resulting in hyperthyroidism after iodine supplementation. IHH is considered by some experts to be an iodine deficiency disorder. In general, the large benefit of iodization programs outweighs the small risk of IHH in iodine-deficient populations.

In iodine sufficiency: In iodine-sufficient populations (e.g., the U.S.), excess iodine intake is most commonly associated with elevated blood levels of thyroid stimulating hormone (TSH), hypothyroidism, and goiter. Although a slightly elevated TSH level does not necessarily indicate inadequate thyroid hormone production, it is the earliest sign of abnormal thyroid function when iodine intake is excessive. In iodine-sufficient adults, elevated TSH levels have been found at iodine intakes between 1,700 and 1,800 mcg/day. In order to minimize the risk of developing hypothyroidism, the Food and Nutrition Board (FNB) of the Institute of Medicine set a tolerable upper level of intake (UL) for iodine at 1,100 mcg/day for adults. Very high (pharmacologic) doses of iodine may also produce thyroid enlargement (goiter) due to increased TSH stimulation of the thyroid gland. Prolonged intakes of more than 18,000 mcg/day (18 mg/day) have been found to increase the incidence of goiter. The UL values for iodine are listed by age group in the table below. The UL is not meant to apply to individuals who are being treated with iodine under medical supervision.

Tolerable Upper Intake Level (UL) for Iodine

Age Group UL (mg/day)
Infants 0-12 months Not possible to establish*
Children 1-3 years 200 mcg/day
Children 4-8 years 300 mcg/day
Children 9-13 years 600 mcg/day
Adolescents 14-18 years 900 mcg/day
Adults 19 years and older 1,100 mcg/day (1.1 mg/day)
*Source of intake should be from food and formula only.

Individuals with increased sensitivity to excess iodine intake: Individuals with iodine deficiency, nodular goiter, or autoimmune thyroid disease may be sensitive to intake levels considered safe for the general population and may not be protected by the UL for iodine intake. Children with cystic fibrosis may also be more sensitive to the adverse effects of excess iodine.

Excess iodine and thyroid cancer: Observational studies have found increased iodine intake to be associated with an increased incidence of thyroid papillary cancer. The reasons for this association are not clear. In populations that were previously iodine deficient, salt iodization programs have resulted in relative increases in thyroid papillary cancers and relative decreases in thyroid follicular cancers. In general, thyroid papillary cancers are less aggressive and have a better prognosis than thyroid follicular cancers.

Drug interactions

Amiodarone, a medication used to prevent abnormal heart rhythms, contains high levels of iodine and may affect thyroid function. Medications used to treat hyperthyroidism, such as propylthiuracil (PTU) and methimazole may increase the risk of hypothyroidism. The use of lithium in combination with pharmacologic doses of potassium iodide may result in hypothyroidism. The use of pharmacologic doses of potassium iodide may decrease the anticoagulant effect of warfarin (coumarin).


The RDA for iodine is sufficient to ensure normal thyroid function. There is presently no evidence that iodine intakes higher than the RDA are beneficial. Most people in the U.S. consume more than sufficient iodine in their diets, making supplementation unnecessary. Given the importance of sufficient iodine during prenatal development and infancy, pregnant and breastfeeding women should consider taking a supplement providing 150 mcg of iodine/day (see Deficiency).

Adults over the age of 65

Because aging has not been associated with significant changes in the requirement for iodine, our recommendation for iodine is not different for older adults.



Iron has the longest and best described history among all the micronutrients. It is a key element in the metabolism of almost all living organisms. In humans, iron is an essential component of hundreds of proteins and enzymes.


Oxygen transport and storage

Heme is an iron-containing compound found in a number of biologically important molecules. Hemoglobin and myoglobin are heme-containing proteins that are involved in the transport and storage of oxygen. Hemoglobin is the primary protein found in red blood cells and represents about two thirds of the body's iron. The vital role of hemoglobin in transporting oxygen from the lungs to the rest of the body is derived from its unique ability to acquire oxygen rapidly during the short time it spends in contact with the lungs and to release oxygen as needed during its circulation through the tissues. Myoglobin functions in the transport and short-term storage of oxygen in muscle cells, helping to match the supply of oxygen to the demand of working muscles.

Electron transport and energy metabolism

Cytochromes are heme-containing compounds that are critical to cellular energy production and therefore, life, through their roles in mitochondrial electron transport. They serve as electron carriers during the synthesis of ATP, the primary energy-storage compound in cells. Cytochrome P450 is a family of enzymes that functions in the metabolism of a number of important biological molecules, as well as the detoxification and metabolism of drugs and pollutants. Nonheme iron-containing enzymes, such as NADH dehydrogenase and succinate dehydrogenase, are also critical to energy metabolism.

Antioxidant and beneficial pro-oxidant functions

Catalase and peroxidases are heme-containing enzymes that protect cells against the accumulation of hydrogen peroxide, a potentially damaging reactive oxygen species (ROS), by catalyzing a reaction that converts hydrogen peroxide to to water and oxygen. As part of the immune response, some white blood cells engulf bacteria and expose them to ROS in order to kill them. The synthesis of one such ROS, hypochlorous acid, by neutrophils is catalyzed by the heme-containing enzyme myeloperoxidase.

Oxygen sensing

Inadequate oxygen (hypoxia), such as that experienced by those who live at high altitudes or those with chronic lung disease, induces compensatory physiologic responses, including increased red blood cell formation, increased blood vessel growth (angiogenesis) and increased production of enzymes utilized in anaerobic metabolism. Under hypoxic conditions transcription factors, known as hypoxia inducible factors (HIF), bind to response elements in genes that encode various proteins involved in compensatory responses to hypoxia and increase their synthesis. Recent research indicates that an iron-dependent prolyl hydroxylase enzyme plays a critical role in regulating HIF and consequently, physiologic responses to hypoxia. When cellular oxygen tension is adequate, newly synthesized HIFa subunits are modified by a prolyl hydroxylase enzyme in an iron-dependent process that targets HIFa for rapid degradation. When cellular oxygen tension drops below a critical threshold, prolyl hydroxylase can no longer target HIFa for degradation, allowing HIFa to bind to HIFb and form an active transcription factor that is able to enter the nucleus and bind to specific response elements on genes.

DNA synthesis

Ribonucleotide reductase is an iron-dependent enzyme that is required for DNA synthesis. Thus, iron is required for a number of vital functions, including growth, reproduction, healing, and immune function.

Regulation of intracellular iron

Iron response elements are short sequences of nucleotides found in the messenger RNA (mRNA) that codes for key proteins in the regulation of iron storage and metabolism. Iron regulatory proteins (IRP) can bind to iron response elements and affect mRNA translation, thereby regulating the synthesis of specific proteins. It has been proposed that when the iron supply is high, more iron binds to IRPs and prevents them from binding to iron response elements on mRNA. When the iron supply is low, less iron binds to IRPs, allowing increased binding of iron response elements. Thus, when less iron is available, translation of mRNA that codes for the iron storage protein, ferritin, is reduced because iron is not available for storage. Translation of mRNA that codes for the key regulatory enzyme of heme synthesis in immature red blood cells is also reduced to conserve iron. In contrast, IRP binding to iron response elements in mRNA that codes for transferrin receptors inhibits mRNA degradation, resulting in increased synthesis of transferrin receptors and increased iron transport to cells.

Nutrient interactions

Vitamin A: Vitamin A deficiency may exacerbate iron deficiency anemia. Vitamin A supplementation has been shown to have beneficial effects on iron deficiency anemia and improve iron status among children and pregnant women. The combination of vitamin A and iron seems to ameliorate anemia more effectively than either iron or vitamin A alone.

Copper: Adequate copper nutritional status appears to be necessary for normal iron metabolism and red blood cell formation. Anemia is a clinical sign of copper deficiency. Animal studies demonstrate a role for copper in iron absorption, and iron has been found to accumulate in the livers of copper deficient animals, indicating that copper is required for iron transport to the bone marrow for red blood cell formation.

Zinc: High doses of iron supplements taken together with zinc supplements on an empty stomach can inhibit the absorption of zinc. When taken with food, supplemental iron does not appear to inhibit zinc absorption. Iron-fortified foods have no effect on zinc absorption.

Calcium: When consumed together in a single meal, calcium has been found to decrease the absorption of iron. However, little effect has been observed on serum ferritin levels (iron stores) with calcium supplement levels ranging from 1,000 to 1,500 mg/day.


Iron deficiency is the most common nutrient deficiency in the U.S. and the world. Three levels of iron deficiency are generally identified and are listed below from least to most severe:

Storage iron depletion: Iron stores are depleted, but the functional iron supply is not limited.

Early functional iron deficiency: The supply of functional iron is low enough to impair red blood cell formation, but not low enough to cause measurable anemia.

Iron deficiency anemia: There is inadequate iron to support normal red blood cell formation, resulting in anemia. The anemia of iron deficiency is characterized as microcytic and hypochromic, meaning red blood cells are measurably smaller than normal and their hemoglobin content is decreased. At this stage of iron deficiency, symptoms may be a result of inadequate oxygen delivery due to anemia and/or sub-optimal function of iron-dependent enzymes. It is important to remember that iron deficiency is not the only cause of anemia, and that the diagnosis or treatment of iron deficiency solely on the basis of anemia may lead to misdiagnosis or inappropriate treatment of the underlying cause. See Folic acid and Vitamin B12 for information on other nutritional causes of anemia.

Symptoms of iron deficiency

Most of the symptoms of iron deficiency are a result of the associated anemia, and may include fatigue, rapid heart rate, palpitations, and rapid breathing on exertion. Iron deficiency impairs athletic performance and physical work capacity in several ways. In iron deficiency anemia, the reduced hemoglobin content of red blood cells results in decreased oxygen delivery to active tissues. Decreased myoglobin levels in muscle cells limit the amount of oxygen that can be delivered to mitochondria for oxidative metabolism. Iron depletion also decreases the oxidative capacity of muscle by diminishing the mitochondrial content of cytochromes and other iron-dependent enzymes required for electron transport and ATP synthesis. Lactic acid production is also increased in iron deficiency. The ability to maintain a normal body temperature on exposure to cold is also impaired in iron-deficient individuals. Severe iron deficiency anemia may result in brittle and spoon-shaped nails, sores at the corners of the mouth, taste bud atrophy, and a sore tongue. In some cases, advanced iron-deficiency anemia may cause difficulty in swallowing due to the formation of webs of tissue in the throat and esophagus. The development of esophageal webs, also known as Plummer-Vinson syndrome, may require a genetic predisposition in addition to iron deficiency. Pica, a behavioral disturbance characterized by the consumption of non-food items, may be a symptom and a cause of iron deficiency.

Individuals at increased risk of iron deficiency

Infants and children between the ages of 6 months and 4 years: A full-term infant's iron stores are usually sufficient to last for 6 months. High iron requirements are due to the rapid growth rates sustained during this period.

Adolescents: Early adolescence is another period of rapid growth. In females, the blood loss that occurs with menstruation adds to the increased iron requirement of adolescence.

Pregnant women: Increased iron utilization by the developing fetus and placenta, as well as blood volume expansion significantly, increase the iron requirement during pregnancy.

Individuals with chronic blood loss: Chronic bleeding or acute blood loss may result in iron deficiency. One milliliter (ml) of blood with a hemoglobin concentration of 150 grams/liter contains 0.5 mg of iron. Thus, chronic loss of very small amounts of blood may result in iron deficiency. A common cause of chronic blood loss and iron deficiency in developing countries is intestinal parasitic infection. Individuals who donate blood frequently, especially menstruating women, may need to increase their iron intake to prevent deficiency because each 500 ml of blood donated contains between 200 and 250 mg of iron.

Individuals with helicobacter pylori infection: H. pylori infection is associated with iron deficiency anemia, especially in children, even in the absence of gastrointestinal bleeding.

Vegetarians: Because iron from plant sources is less efficiently absorbed than that from animal sources, the U.S. Food and Nutrition Board (FNB) has estimated that the bioavailability of iron from a vegetarian diet is only 10%, while it is 18% from a mixed diet. Therefore, the recommended dietary allowance (RDA) for iron from a completely vegetarian diet should be adjusted as follows: 14 mg/day for adult men and postmenopausal women, 33 mg/day for premenopausal women, and 26 mg/day for adolescent girls.

Individuals who engage in regular, intense exercise: Daily iron losses have been found to be greater in athletes involved in intense endurance training. This may be due to increased microscopic bleeding from the gastrointestinal tract or increased fragility and hemolysis of red blood cells. The FNB estimates that the average requirement for iron may be 30% higher for those who engage in regular intense exercise.

The Recommended Dietary Allowance (RDA)

The RDA for iron was revised in 2001 and is based on the prevention of iron deficiency and maintenance of adequate iron stores in individuals eating a mixed diet.

Recommended Dietary Allowance (RDA) for Iron

Life Stage Age Males (mg/day) Females (mg/d)
Infants 0-6 months 0.27 (AI) 0.27 (AI)
Infants 7-12 months 11 11
Children 1-3 years 7 7
Children 4-8 years 10 10
Children 9-13 years 8 8
Adolescents 14-18 years 11 15
Adults 19-50 years 8 18
Adults 51 years and older 8 8
Pregnancy all ages 27
Breastfeeding 18 years and younger 10
Breastfeeding 19 years and older 9


The following health problems and diseases may be prevented through the treatment or prevention of iron deficiency.

Impaired intellectual development in children

Most observational studies have found relationships between iron deficiency anemia in children and poor cognitive development, poor school achievement, and behavior problems. However, it is difficult to separate the effects of iron deficiency anemia from other types of deprivation in such studies. In anemic children under the age of 2 years, only one randomized double blind trial found a significant benefit of iron supplementation on indices of cognitive development. However, 4 randomized controlled trials found a significant benefit of iron supplementation on cognition and school achievement in children over 2 years of age, while 2 studies found no effect. Several possible mechanisms link iron deficiency anemia to altered cognition. Anemic children tend to move around and explore their environment less than children without anemia, which may lead to developmental delays. Conduction of auditory and optic nerve impulses to the brain has been found to be slower in children with iron deficiency anemia. This effect could be associated with changes in nerve myelination, which have been observed in iron deficient animals. Neurotransmitter synthesis may also be sensitive to iron deficiency.

Lead toxicity

Iron deficiency may increase the risk of lead poisoning in children. A number of epidemiological studies have found iron deficiency to be associated with increased blood lead levels in young children. Iron deficiency and lead poisoning share a number of the same risk factors, but iron deficiency has been found to increase the intestinal absorption of lead in humans and animals. However, the use of iron supplementation in lead poisoning should be reserved for those individuals who are truly iron deficient or for those individuals with continuing lead exposure, such as continued residence in lead-exposed housing.

Pregnancy complications

Epidemiological studies provide strong evidence of an association between severe anemia in pregnant women and adverse pregnancy outcomes, such as low birth weight, premature birth, and maternal mortality. Iron deficiency can be a major contributory factor to severe anemia, but evidence that iron deficiency anemia is a causal factor in poor pregnancy outcomes is still lacking. Nevertheless, most experts consider the control of maternal anemia to be an important part of prenatal health care. Elevated hemoglobin, especially in later pregnancy, is also associated with poor pregnancy outcomes, but there is no evidence that this association is related to high iron intakes or iron supplementation. Rather, elevated hemoglobin in pregnancy is more likely to be explained by underlying conditions like pregnancy induced hypertension or preeclampsia, which are well known to contribute to poor pregnancy outcomes.

Impaired immune function

Iron is required by most infectious agents, as well as by the infected host in order to mount an effective immune response. Sufficient iron is critical to several immune functions, including the differentiation and proliferation of T lymphocytes and the generation of reactive oxygen species (ROS) by iron-dependent enzymes, which are used for killing pathogens. During an acute inflammatory response, serum iron levels decrease while levels of ferritin (the iron storage protein) increase, suggesting that sequestering iron from pathogens is an important host response to infection. Despite the critical functions of iron in the immune response, the nature of the relationship between iron deficiency and susceptibility to infection, especially with respect to malaria, remains controversial. High-dose iron supplementation of children residing in the tropics has been associated with increased risk of clinical malaria and other infections, such as pneumonia. Studies in cell culture and animals suggest that the survival of infectious agents that spend part of their life cycle within host cells, such as plasmodia (malaria) and mycobacteria (tuberculosis) may be enhanced by iron therapy. Controlled clinical studies are needed to determine the appropriate use of iron supplementation in regions where malaria is common, as well as in the presence of infectious diseases, such as HIV, tuberculosis, and typhoid.


Restless legs syndrome

Restless legs syndrome (RLS) is a neurologic movement disorder that is often associated with sleep problems. People with RLS experience unpleasant sensations resulting in an irresistible urge to move their legs. These sensations are more common at rest and often interfere with sleep. RLS occurs in some people with iron deficiency and some RLS patients benefit from iron supplementation. Recently, ferritin levels were found to be lower and transferrin levels higher in the cerebrospinal fluid of individuals with RLS, suggesting that low brain iron concentrations may play a role in RLS. Magnetic resonance imaging (MRI) measurements of brain iron concentrations also indicate that iron insufficiency in certain regions of the brain may occur in patients with RLS. The mechanism by which low brain iron concentration contributes to RLS is not known, but may be related to the fact that the activity of an iron-dependent enzyme (tyrosine hydroxylase) is a limiting factor in the synthesis of the neurotransmitter, dopamine.


Food Sources

The amount of iron in food (or supplements) that is absorbed and used by the body is influenced by the iron nutritional status of the individual and whether or not the iron is in the form of heme. Because it is absorbed by a different mechanism than nonheme iron, heme iron is more readily absorbed and its absorption is less affected by other dietary factors. Individuals who are anemic or iron deficient absorb a larger percentage of the iron they consume (especially nonheme iron) than individuals who are not anemic and have sufficient iron stores.

Heme iron: Heme iron comes mainly from hemoglobin and myoglobin in meat, poultry, and fish. Although heme iron accounts for only 10-15% of the iron found in the diet, it may provide up to one third of total absorbed dietary iron. The absorption of heme iron is less influenced by other dietary factors than that of nonheme iron.

Nonheme iron: Plants, dairy products, meat, and iron salts added to foods and supplements are all sources of nonheme iron. The absorption of nonheme iron is strongly influenced by enhancers and inhibitors present in the same meal.

Enhancers of nonheme iron absortion

Vitamin C (ascorbic acid): Vitamin C strongly enhances the absorption of nonheme iron by reducing dietary ferric iron (Fe3+) to ferrous iron (Fe2+) and forming an absorbable iron-ascorbic acid complex.

Other organic acids: Citric, malic, tartaric, and lactic acids have some enhancing effects on nonheme iron absorption.

Meat, fish, and poultry: Aside from providing highly absorbable heme iron, meat, fish, and poultry also enhance nonheme iron absorption. The mechanism for this enhancement of nonheme iron absortion is not clear.

Inhibitors of nonheme iron absorption

Phytic acid (phytate): Phytic acid is present in legumes, grains, and rice and is an inhibitor of nonheme iron absorption. Small amounts of phytic acid (5 to 10 mg) can reduce nonheme iron absorption by 50%. The absorption of iron from legumes, such as soybeans, black beans, lentils, mung beans, and split peas, has been shown to be as low as 2%.

Polyphenols: Polyphenols, found in some fruits, vegetables, coffee, tea, wines, and spices, can markedly inhibit the absorption of nonheme iron. This effect is reduced by the presence of vitamin C.

Soy protein: Soy protein, such as that found in tofu, has an inhibitory effect on iron absorption that is independent of its phytic acid content.

National surveys in the U.S. indicate that the average dietary iron intake is 16-18 mg/day in men, 12 mg/day in pre- and postmenopausal women, and about 15 mg/day in pregnant women. Thus, the majority of premenopausal and pregnant women in the U.S. consume less than the RDA for iron and many men consume more than the RDA. In the U.S., most grain products are fortified with iron. The iron content of some relatively iron-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 Iron content (mg)
Beef 3 ounces*, cooked 2.31
Chicken, dark meat 3 ounces, cooked 1.13
Oysters 6 medium 5.04
Shrimp 8 large, cooked 1.36
Tuna, light 3 ounces, canned 1.30
Black-strap molasses 1 tablespoon 3.50
Raisin bran cereal 1 cup, dry 5.00
Raisins, seedless 1 small box (1.5 ounces) 0.89
Prune juice 6 fluid ounces 2.27
Prunes, dried ~ 5 prunes (1.5 ounces) 1.06
Potato, with skin 1 medium potato, baked 2.75
Kidney beans 1/2 cup, cooked 2.60
Lentils 1/2 cup, cooked 3.30
Tofu, firm 1/4 block (~1/2 cup) 6.22
Cashew nuts 1 ounce 1.70
*A three-ounce serving of meat is about the size of a deck of cards.


Iron supplements are indicated for the prevention and treatment of iron deficiency. Individuals who are not at risk of iron deficiency (e.g., adult men and postmenopausal women) should not take iron supplements without an appropriate medical evaluation for iron deficiency. A number of iron supplements are available, and different forms provide different proportions of elemental iron. Ferrous sulfate (heptahydrate) is 22% elemental iron; ferrous sulfate (monohydrate) is 33% elemental iron; ferrous gluconate is 12% elemental iron; ferrous fumarate is 33% elemental iron  if not stated otherwise, all of the iron doses discussed in this presentation represent elemental iron.


Several genetic disorders may lead to pathological accumulation of iron in the body. Hereditary hemochromatosis results in iron overload despite normal iron intake, while sub-Saharan African hemochromatosis appears to require a combination of high iron intake and a genetic predisposition. Iron overload due to prolonged iron supplementation is very rare in healthy individuals without a genetic predisposition. This fact emphasizes the degree to which the body's tight control of intestinal iron absorption protects it from the adverse effects of iron overload. However, supplementation of individuals who are not iron deficient should be avoided due to the frequency of undetected hereditary hemochromatosis and recent concerns about the more subtle effects of chronic excess iron intake (see Safety).

Hereditary hemochromatosis

Up to 1 in 200 individuals of northern European descent are affected by a genetic disorder known as hereditary hemochromatosis (HH). It is characterized by iron deposition in the liver and other tissues as a result of a small increase in intestinal iron absorption over many years. If untreated, tissue iron accumulation may lead to cirrhosis of the liver, diabetes, heart muscle damage (cardiomyopathy), or arthritis. HH was known to be a genetic disorder affecting intestinal iron absorption for many years, but the gene (HFE) and the mutation resulting in HH were only identified in 1996. At present, the exact role of the protein encoded by the HFE gene in intestinal iron absorption is not well understood. Iron overload in HH is treated by phlebotomy, the removal of 500 ml of blood at a time, at intervals determined by the severity of the iron overload. Individuals with HH are advised to avoid supplemental iron, but are not generally advised to avoid iron-rich foods. Alcohol consumption is strongly discouraged due to the increased risk of cirrhosis of the liver. Genetic testing, which requires a blood sample, is available for those who may be at risk for HH, for example, individuals with a family history of hemochromatosis.

Sub-Saharan African hemochromatosis

Iron overload in black people of South Africa is associated with chronic exposure to diets containing too much iron derived mainly from cooking pots and steel barrels used to ferment beer. This form of iron overload is usually more severe in adult men, whose beer consumption tends to be higher and whose iron intake may exceed 100 mg/day. Like HH, it may also result in cirrhosis of the liver or diabetes. Unlike HH, Sub-Saharan African hemochromatosis appears to require high iron intake in association with a genetic factor that has not yet been identified. African Americans may also incur significant iron overload, and it has been suggested that the mutation associated with Sub-Saharan African hemochromatosis may also occur in Americans of African descent. Unfortunately, the true incidence and the causes of iron overload among African Americans have yet to be determined.

Hereditary anemias:

Iron overload may occur in individuals with severe hereditary anemias that are not caused by iron deficiency. Excessive dietary absorption of iron may occur in response to the body's continued efforts to form red blood cells. Anemic patients at risk of iron overload include those with sideroblastic anemia, pyruvate kinase deficiency, and thalassemia major, especially when they are treated with numerous transfusions. Patients with hereditary spherocytosis and thalassemia minor do not usually develop iron overload, unless they are misdiagnosed as having iron deficiency and treated with large doses of iron over many years. The thalassemias (major and minor) are common in individuals of Mediterranean descent. It has been hypothesized that a Mediterranean form of iron overload, distinct from HH, also exists.



Overdose: Accidental overdose of iron-containing products is the single largest cause of poisoning fatalities in children under 6 years of age. Although the oral lethal dose of elemental iron is approximately 200-250 mg/kg of body weight, considerably less has been fatal. Symptoms of acute toxicity may occur with iron doses of 20-60 mg/kg of body weight. Iron overdose is an emergency situation because the severity of iron toxicity is related to the amount of elemental iron absorbed. Acute iron poisoning produces symptoms in four stages: 1) Within 1-6 hours of ingestion, symptoms may include nausea, vomiting, abdominal pain, tarry stools, lethargy, weak and rapid pulse, low blood pressure, fever, difficulty breathing, and coma. 2) If not immediately fatal, symptoms may subside for about 24 hours. 3) Symptoms may return 12 to 48 hours after iron ingestion and may include serious signs of failure in the following organ systems: cardiovascular, kidney, liver, hematologic (blood), and central nervous systems. 4) Long-term damage to the central nervous system, liver (cirrhosis), and stomach may develop 2 to 6 weeks after ingestion.

Adverse effects: At therapeutic levels for iron deficiency, iron supplements may cause gastrointestinal irritation, nausea, vomiting, diarrhea, or constipation. Stools will often appear darker in color. Iron-containing liquids can temporarily stain teeth, but diluting the liquid helps to prevent this effect. Taking iron supplements with food instead of on an empty stomach may relieve gastrointestinal effects. The Food and Nutrition Board (FNB) of the Institute of Medicine based the tolerable upper intake level (UL) for iron on the prevention of gastrointestinal distress. The UL for adolescents and adults over the age of 14 years, including pregnant and breastfeeding women is 45 mg/day. It should be noted that the UL is not meant to apply to individuals being treated with iron under close medical supervision. Individuals with hereditary hemochromatosis or other conditions of iron overload, as well as individuals with alcoholic cirrhosis and other liver diseases, may experience adverse effects at iron intake levels below the UL.

Tolerable Upper Intake Level (UL) for Iron

Age Group UL (mg/day)
Infants 0-12 months Not possible to establish*
Children 1-13 years 40
Adolescents 14-18 years 45
Adults 19 years and older 45
*Source of intake should be from food and formula only.

Diseases that have been associated with iron excess

Cardiovascular diseases: Animal studies suggest a role for iron-induced oxidative stress in the pathology of atherosclerosis and myocardial infarction (heart attack). However, epidemiological studies of iron nutritional status and cardiovascular diseases in humans have yielded conflicting results. A systematic review of 12 prospective cohort studies including 7,800 cases of coronary heart disease (CHD) did not find good evidence to support the existence of strong associations between a number of different measures of iron status and CHD. Serum ferritin concentration is the measure of iron status thought to best reflect iron stores. However, the same review found no difference in the risk of CHD between individuals with serum ferritin concentrations of 200 mcg/liter or higher and those with ferritin concentrations of less than 200 mcg/liter in the 5 prospective studies that measured serum ferritin. Two large prospective studies found increased dietary heme iron, but not total dietary iron, to be associated with increased risk of myocardial infarction. When iron stores are high, nonheme iron absorption is inhibited more effectively than heme iron absorption, suggesting that iron from animal sources may play a more important role than total iron intake in CHD risk. Although the relationship between iron stores and CHD requires further clarification, it would be prudent for those who are not at risk of iron deficiency (e.g., adult men and postmenopausal women) to avoid excess iron intake.

Cancer: A dramatically increased risk of liver cancer (hepatocellular carcinoma) in individuals with cirrhosis due to iron overload in hereditary hemochromatosis has been well documented. However, the relationship between dietary iron and cancer risk in individuals without hemochromatosis is less clear. Several epidemiological studies reported associations between measures of increased iron status and the incidence of colorectal cancer or the occurrence of precancerous polyps (adenomas), but the associations were not consistent. Dietary iron intake appears to be more consistently related to the risk of colorectal cancer than measures of iron status or iron stores. Increased red meat consumption has been associated with an increased risk of colorectal cancer, but there are a number of potential mechanisms by which increased meat consumption could affect cancer risk other than increasing iron intake. For example, increased red meat consumption increases the secretion of bile acids, which can be toxic to colonic cells, and increases exposure to carcinogenic compounds generated when meat is cooked. Increased iron in the contents of the colon, rather than increased body iron stores, could increase the risk of colon cancer by exposing colonic cells to potentially damaging reactive oxygen species derived from iron-catalyzed reactions, especially in the presence of a high fat diet. Although this possibility is presently under investigation, the relationship between dietary iron intake, iron stores, and the risk of colorectal cancer remains unclear. For more information about colorectal cancer, see the Linus Pauling Institute Newsletter article, Colorectal Cancer: Early Detection and Prevention.

Neurodegenerative diseases: Iron is required for normal brain and nerve function through its involvement in cellular metabolism, as well as the synthesis of neurotransmitters and myelin. However, accumulation of excess iron can result in increased oxidative stress, and the brain is particularly susceptible to oxidative damage. Iron accumulation and oxidative injury are presently under consideration as potential contributors to a number of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The abnormal accumulation of iron in the brain does not appear to be a result of increased dietary iron, but rather, a disruption in the complex process of cellular iron regulation. Although the mechanisms for this disruption in iron regulation are not yet known, it is presently an active area of biomedical research.

Drug Interactions

Medications that decrease stomach acidity, such as antacids, histamine (H2) receptor antagonists (e.g., cimetidine, ranitidine), and proton pump inhibitors (e.g., omeprazole, lansoprazole), may impair iron absorption. Taking iron supplements at the same time as the following medications may result in decreased absorption and efficacy of the medication: levodopa, levothyroxine, methyldopa, penicillamine, quinolones, tetracyclines, and bisphosphonates. Therefore, it is best to take these medications two hours apart from iron supplements. Cholestyramine resin, used to lower blood cholesterol levels, should also be taken two hours apart from iron supplements because it interferes with iron absorption. Allopurinol, a medication used to treat gout, may increase iron storage in the liver and should not be used in combination with iron supplements.


Following the most recent RDA for iron should provide sufficient iron to prevent deficiency without causing adverse effects in most individuals. Although sufficient iron can be obtained through a varied diet, a considerable number of people do not consume adequate iron to prevent deficiency. A multivitamin/multimineral supplement containing 100% of the daily value (DV) for iron provides 18 mg of elemental iron. While this amount of iron may be beneficial for premenopausal women, it is well above the RDA for men and most postmenopausal women.

Adult men and postmenopausal women

Since hereditary hemochromatosis is relatively common and the effects of long-term dietary iron excess on chronic disease risk are not yet clear, men and postmenopausal women who are not at risk of iron deficiency should take a multivitamin/mineral supplement without iron. A number of multivitamins formulated specifically for men or those over 50 years of age do not contain iron.

Adults over the age of 65

A recent study in an elderly population found that high iron stores were much more common than iron deficiency (39). Thus, older adults should not generally take nutritional supplements containing iron unless they have been diagnosed with iron deficiency. Moreover, it is extremely important to determine the underlying cause of the iron deficiency, rather than simply treating it with iron supplements



Manganese is a mineral element that is both nutritionally essential and potentially toxic. The derivation of its name from the Greek word for magic remains appropriate because scientists are still working to understand the diverse effects of manganese deficiency and manganese toxicity in living organisms.


Manganese (Mn) plays an important role in a number of physiologic processes as a constituent of some enzymes and an activator of other enzymes.

Antioxidant function

Manganese superoxide dismutase (MnSOD) is the principal antioxidant enzyme of mitochondria. Because mitochondria consume over 90% of the oxygen used by cells, they are especially vulnerable to oxidative stress. The superoxide radical is one of the reactive oxygen species produced in mitochondria during ATP synthesis. MnSOD catalyzes the conversion of superoxide radicals to hydrogen peroxide, which can be reduced to water by other antioxidant enzymes.


A number of manganese-activated enzymes play important roles in the metabolism of carbohydrates, amino acids, and cholesterol. Pyruvate carboxylase, a manganese-containing enzyme, and phosphoenolpyruvate carboxykinase (PEPCK), a manganese-activated enzyme, play critical roles in gluconeogenesis— the production of glucose from non-carbohydrate precursors. Arginase, another manganese-containing enzyme, is required by the liver for the urea cycle, a process that detoxifies ammonia generated during amino acid metabolism.

Bone development

Manganese deficiency results in abnormal skeletal development in a number of animal species. Manganese is the preferred cofactor of enzymes called glycosyltransferases, which are required for the synthesis of proteoglycans that are needed for the formation of healthy cartilage and bone.

Wound healing

Wound healing is a complex process that requires increased production of collagen. Manganese is required for the activation of prolidase, an enzyme that functions to provide the amino acid, proline, for collagen formation in human skin cells. A genetic disorder known as prolidase deficiency results in abnormal wound healing among other problems, and is characterized by abnormal manganese metabolism Glycosaminoglycan synthesis, which requires manganese-activated glycosyltranserases, may also play an important role in wound healing.

Nutrient interactions

Iron: Although the specific mechanisms for manganese absorption and transport have not been determined, some evidence suggests that iron and manganese can share common absorption and transport pathways. Absorption of manganese from a meal is reduced as the meal's iron content is increased. Iron supplementation (60 mg/day for 4 months) was associated with decreased blood manganese levels and decreased MnSOD activity in white blood cells, indicating a reduction in manganese nutritional status. An individual's iron status can affect manganese bioavailability. Intestinal absorption of manganese is increased during iron deficiency, and increased iron stores (ferritin levels) are associated with decreased manganese absorption. The finding that men generally absorb less manganese than women may be related to the fact that men usually have higher iron stores than women.

Magnesium: Supplemental magnesium (200 mg/day) decreased manganese bioavailability slightly, either by decreasing manganese absorption or by increasing its loss in healthy adults.

Calcium: In one set of studies, supplemental calcium (500 mg/day) resulted in slightly lower manganese bioavailability in healthy adults. As a source of calcium, milk had the least effect, while calcium carbonate and calcium phosphate had the greatest effect. Several others studies have found the effect of supplemental calcium on manganese metabolism to be minimal.


Manganese deficiency has been observed in a number of animal species. Signs of manganese deficiency include impaired growth, impaired reproductive function, skeletal abnormalities, impaired glucose tolerance, and altered carbohydrate and lipid metabolism. In humans, demonstration of a manganese deficiency syndrome has been less clear. A child on long-term total parenteral nutrition (TPN) that lacked manganese developed bone demineralization and impaired growth that were corrected by manganese supplementation. Young men who were fed a low-manganese diet developed decreased serum cholesterol levels and a transient skin rash. Blood calcium, phosphorus, and alkaline phosphatase levels were also elevated, which may indicate increased bone remodeling as a consequence of insufficient dietary manganese. Young women fed a manganese-poor diet developed mildly abnormal glucose tolerance in response to an intravenous (IV) infusion of glucose.

The Adequate Intake (AI)

Because there was not enough information on manganese requirements to set a Recommended Dietary Allowance (RDA), the Food and Nutrition Board (FNB) of the Institute of Medicine set an adequate intake level (AI). Since overt manganese deficiency has not been documented in humans eating natural diets, the FNB based the AI on average dietary intakes of manganese determined by the Total Diet Study — an annual survey of the mineral content of representative diets of Americans (4). AI values for manganese are listed in the table below in milligrams (mg)/day by age and gender.

Adequate Intake (AI) for Manganese

Life Stage Age Males (mg/day) Females (mg/day)
Infants 0-6 months 0.003 0.003
Infants 7-12 months 0.6 0.6
Children 1-3 years 1.2 1.2
Children 4-8 years 1.5 1.5
Children 9-13 years 1.9 1.6
Adolescents 14-18 years 2.2 1.6
Adults 19 years and older 2.3 1.8
Pregnancy all ages 2.0
Breastfeeding all ages 2.6


Low dietary manganese or low levels of manganese in blood or tissue have been associated with several chronic diseases. Although manganese insufficiency is not currently thought to cause the diseases discussed below, more research may be warranted to determine whether suboptimal manganese nutritional status contributes to certain disease processes.


Women with osteoporosis have been found to have decreased plasma levels of manganese and an enhanced plasma response to an oral dose of manganese, suggesting they may have lower manganese status than women without osteoporosis. A study in healthy postmenopausal women found that a supplement containing manganese (5 mg/day), copper (2.5 mg/day), and zinc (15 mg/day) in combination with a calcium supplement (1,000 mg/day) was more effective than the calcium supplement alone in preventing spinal bone loss over a period of 2 years. However, the presence of other trace elements in the supplement makes it impossible to determine whether manganese supplementation was the beneficial agent for maintaining bone mineral density.

Diabetes mellitus

Manganese deficiency results in glucose intolerance similar to diabetes mellitus in some animal species, but studies examining the manganese status of diabetic humans have generated mixed results. Whole blood manganese levels did not differ significantly between 57 diabetics and 28 non-diabetic controls. However, urinary manganese excretion tended to be slightly higher in 185 diabetics compared to 185 non-diabetic controls. Additionally, a study of functional manganese status found the activity of the antioxidant enzyme, MnSOD, to be lower in the white blood cells of diabetics than in those of non-diabetic controls. Neither 15 mg nor 30 mg of oral manganese improved glucose tolerance in diabetics or non-diabetic controls when given at the same time as an oral glucose challenge. Although manganese appears to play a role in glucose metabolism, there is little evidence that manganese supplementation improves glucose tolerance in diabetic or non-diabetic individuals.

Epilepsy (seizure disorders)

Manganese deficient rats are more susceptible to seizures, and rats that are genetically prone to epilepsy have lower than normal brain and blood manganese levels. Certain subgroups of humans with epilepsy have been found to have lower whole blood manganese levels than non-epileptic controls. One study found blood manganese levels of individuals with epilepsy of unknown origin to be lower than those of individuals whose epilepsy was induced by trauma (e.g., head injury) or disease, suggesting a possible genetic relationship between epilepsy and abnormal manganese metabolism. While manganese deficiency does not appear to be a cause of epilepsy in humans, the relationship between manganese metabolism and epilepsy deserves further research.


Food sources

Estimated average dietary manganese intakes in the U.S. range from 2.1-2.3 mg/day for men and 1.6-1.8 mg/day for women. People eating vegetarian diets and western diets emphasizing whole grains may have manganese intakes as high as 10.9 mg/day. Rich sources of manganese include whole grains, nuts, leafy vegetables, and teas. Foods high in phytic acid, such as beans, seeds, nuts, whole grains, and soy products, or foods high in oxalic acid, such as cabbage, spinach, and sweet potatoes, may slightly inhibit manganese absorption. Although teas are rich sources of manganese, the tannins present in tea may moderately reduce the absorption of manganese. The manganese content of some manganese-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 Manganese (mg)
Pineapple, raw 1/2 cup, diced 1.28
Pineapple juice 1/2 cup (4 ounces) 1.24
Pecans 1 ounce 1.12
Almonds 1 ounce 0.74
Peanuts 1 ounce 0.59
Instant oatmeal (prepared with water) 1 packet 1.20
Raisin bran cereal 1 cup 1.88
Brown rice, cooked 1/2 cup 0.88
Whole wheat bread 1 slice 0.65
Pinto beans, cooked 1/2 cup 0.48
Lima beans, cooked 1/2 cup 0.48
Navy beans, cooked 1/2 cup 0.51
Spinach, cooked 1/2 cup 0.84
Sweet potato, cooked 1/2 cup, mashed 0.55
Tea (green) 1 cup (8 ounces) 0.41-1.58
Tea (black) 1 cup (8 ounces) 0.18-0.77


Several forms of manganese are found in supplements, including manganese gluconate, manganese sulfate, manganese ascorbate, and amino acid chelates of manganese. Manganese is available as a stand-alone supplement or in combination products. Relatively high levels of manganese ascorbate may be found in a bone/joint health product containing chondroitin sulfate and glucosamine hydrochloride (see Safety).



Inhaled manganese: Manganese toxicity may result in multiple neurologic problems and is a well-recognized health hazard for people who inhale manganese dust (1,4). Unlike ingested manganese, inhaled manganese is transported directly to the brain before it can be metabolized in the liver. The symptoms of manganese toxicity generally appear slowly over a period of months to years. In its worst form, manganese toxicity can result in a permanent neurological disorder with symptoms similar to those of Parkinson's disease, including tremors, difficulty walking, and facial muscle spasms. This syndrome is sometimes preceded by psychiatric symptoms, such as irritability, aggressiveness, and even hallucinations.

Methylcyclopentadienyl manganese tricarbonyl (MMT): MMT is a manganese-containing compound used in gasoline as an anti-knock additive. Although it has been used for this purpose in Canada for more than 20 years, uncertainty about adverse health effects from inhaled exhaust emissions kept the U.S. Environmental Protection Agency (EPA) from approving its use in unleaded gasoline. In 1995, a U.S. court decision made MMT available for widespread use in unleaded gasoline. A recent study in Montreal, where MMT had been used for more than 10 years, found airborne manganese levels to be similar to those in areas where MMT was not used. However, the impact of long-term exposure to low levels of MMT combustion products has not been thoroughly evaluated and will require additional study.

Ingested manganese: Limited evidence suggests that high manganese intakes from drinking water may be associated with neurological symptoms similar to those of Parkinson's disease. Severe neurological symptoms were reported in 25 people who drank water contaminated with manganese and probably other contaminants from dry cell batteries for 2-3 months. Water manganese levels were found to be 14 mg/liter almost 2 months after symptoms began and may have already been declining (1). A study of older adults in Greece found a high prevalence of neurological symptoms in those exposed to water manganese levels of 1.8-2.3 mg/liter, while a study of people in Germany drinking water with manganese levels ranging from 0.3-2.2 mg/liter found no evidence of increased neurological symptoms compared to those drinking water containing less than 0.05 mg/liter. Manganese in drinking water may be more bioavailable than manganese in food. However, none of the studies measured dietary manganese, so total manganese intake in these cases is unknown (1,4). In the U.S., the EPA recommends 0.05 mg/liter as the maximum allowable manganese concentration in drinking water.

A single case of manganese toxicity was reported in a person who took large amounts of mineral supplements for years, while another case was reported as a result of taking a Chinese herbal supplement. Manganese toxicity resulting from foods alone has not been reported in humans, even though certain vegetarian diets could provide up 20 mg/day of manganese.

Individuals with increased susceptibility to manganese toxicity

Chronic liver disease: Manganese is eliminated from the body mainly in bile. Thus, impaired liver function may lead to decreased manganese excretion. Manganese accumulation in individuals with cirrhosis or liver failure may contribute to neurological problems and Parkinson's disease-like symptoms.

Newborns: The newborn brain may be more susceptible to manganese toxicity due to a greater expression of receptors for the manganese transport protein (transferrin) in developing nerve cells and the immaturity of the liver's bile elimination system.

Due to the severe implications of manganese neurotoxicity the Food and Nutrition Board (FNB) of the Institute of Medicine set very conservative upper levels of intake (UL) for manganese, which are listed in the table below.

Tolerable Upper Intake Level (UL) for Manganese

Age Group UL (mg/day)
Infants 0-12 months Not possible to establish*
Children 1-3 years 2
Children 4-8 years 3
Children 9-13 years 6
Adolescents 14-18 years 9
Adults 19 years and older 11
*Source of intake should be from food and formula only.

Drug interactions

Magnesium-containing antacids and laxatives and the antibiotic medication, tetracycline, may decrease the absorption of manganese if taken together with manganese-containing foods or supplements.

High levels of manganese in supplements marketed for bone/joint health: Two recent studies have found that supplements containing a combination of glucosamine hydrochloride, chondroitin sulfate, and manganese ascorbate are beneficial in relieving pain due to mild or moderate osteoarthritis of the knee when compared to a placebo. The dose of elemental manganese supplied by the supplements was 30 mg/day for 8 weeks in one study and 40 mg/day for 6 months in the other. No adverse effects were reported during either study, and blood manganese levels were not measured. Neither study compared the treatment containing manganese ascorbate to a treatment containing glucosamine hydrochloride and chondroitin sulfate without manganese ascorbate, so it is impossible to determine whether the supplement would have resulted in the same benefit without high doses of manganese.


The adequate intake (AI) for manganese (2.3 mg/day for adult men and 1.8 mg/day for adult women) appears sufficient to prevent deficiency in most individuals. The daily intake of manganese most likely to promote optimum health is not known. 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 2 mg/day of manganese in addition to that in foods. Because of the potential for toxicity and the lack of information regarding benefit, manganese supplementation beyond 100% of the DV (2 mg/day) is not recommended. There is presently no evidence that the consumption of a manganese-rich plant-based diet results in manganese toxicity.

Adults over the age of 65

The requirement for manganese is not known to be higher for older adults. However, liver disease is more common in older adults and may increase the risk of manganese toxicity by decreasing the elimination of manganese from the body (see Toxicity). Manganese supplementation beyond 100% of the DV (2 mg/day) is not recommended.



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. Since then, zinc insufficiency has been recognized by a number of experts as an important public health issue, especially in developing countries.


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.

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.

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. 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.

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.

Nutrient Interactions:


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.


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.


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, 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. 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. 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.


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. 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. For a more detailed discussion of the relationship of zinc deficiency to health problems, see Disease Prevention.

Individuals at risk of zinc deficiency:

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 (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.

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


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. 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. 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).

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. 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. 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.

Impaired immune system function

Adequate zinc intake is essential in maintaining the integrity of the immune system, and zinc deficient individuals are known to experience increased susceptibility to a variety of infectious agents.

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. 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.

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.

Malaria: Several studies have indicated that zinc supplementation may reduce the incidence of clinical attacks of malaria in children. 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%. 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.

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. 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. 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. 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. 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.


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. 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, another study found zinc acetate lozenges no different than placebo in reducing the duration or severity of cold symptoms.

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.

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, two other placebo-controlled studies found intranasal zinc to be of no benefit. 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. Of concern are several case reports of individuals experiencing loss of the sense of smell (anosmia) after using intranasal zinc as a cold remedy. 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. 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. 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. 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.

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. 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. 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. Presently, the influence of zinc on glucose metabolism requires further study before high-dose zinc supplementation can be advocated for diabetics.


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. 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. 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. These results indicate that further research is necessary to determine optimal zinc intakes for HIV-infected individuals.


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. 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. 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.


A number of zinc supplements are available, including zinc acetate, zinc gluconate, zinc picolinate, and zinc sulfate. Zinc picolinate has been promoted as a more absorbable form of zinc, but there is little data to support this idea in humans. Limited work in animals suggests that increased intestinal absorption of zinc picolinate may be offset by increased elimination.



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.

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.

Tolerable Upper Intake Level (UL) for Zinc

Age Group UL (mg/day)
Infants 0-6 months 4
Infants 7-12 months 5
Children 1-3 years 7
Children 4-8 years 12
Children 9-13 years 23
Adolescents 14-18 years 34
Adults 19 years and older 40

Intranasal zinc is known to cause a loss of the sense of smell (anosmia) in laboratory animals, and there have been several case reports of individuals who developed anosmia after using intranasal zinc gluconate. 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. 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.


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 provide15 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.


Disclaimer: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, prescribe for, treat, prevent, mitigate or cure any disease. Consumers are cautioned to read all labels and follow all directions. You should always consult with your physician before using these or any such products. Pregnant or lactating women, or anyone with any illness should consult with their medical doctor prior to taking this product.

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