Zinc as a therapeutic supplement

• DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.
• PRINCIPAL PROPOSED USES: Colds, general nutritional supplementation, macular degeneration
• OTHER PROPOSED USES: Acne, anorexia nervosa, attention deficit disorder, benign prostatic hyperplasia, cold sores, depression, diabetes, diarrhea, eczema, enhancing mental function in seniors, human immunodeficiency virus support, impotence, prostatitis, radiation therapy support, rheumatoid arthritis, sickle cell anemia, tinnitus, ulcers

Overview

Zinc is an important element found in every cell of the body. More than three hundred enzymes in the body need zinc to function properly. Although the amount of zinc needed in the daily diet is tiny, it is very important that individuals meet this requirement. However, evidence suggests that many people do not get enough. Mild zinc deficiency is fairly common, especially in women, adolescents, infants, and older adults, so taking a zinc supplement at nutritional doses may be beneficial for some, on a doctor's recommendation.

However, taking too much zinc can cause toxicity. This article discusses the possible uses of zinc at various doses. People should always talk to a doctor before beginning to use any supplement.

Requirements and Sources

The official US recommendations (in milligrams, or mg) for daily intake of zinc are as follows:

Infants up to six months (2 mg) and seven to twelve months (3 mg); children between one and three years (3 mg), between four and eight years (5 mg); and between nine and thirteen years (8 mg); males fourteen years and older (11 mg); females aged fourteen to eighteen years (9 mg); women older than nineteen (8 mg); pregnant girls fourteen to eighteen (12 mg) and pregnant women over nineteen (11 mg); and nursing girls (13 mg) and nursing women (12 mg).

Various drugs may reduce zinc levels in the body by inhibiting absorption or increasing excretion. These include captopril and possibly other angiotensin-converting enzyme (ACE) inhibitors, oral contraceptives, thiazide diuretics, and drugs that reduce stomach acid, including H2 blockers and proton pump inhibitors. Certain nutrients, including calcium, soy, manganese, copper, and iron, may also inhibit zinc absorption. Contrary to previous reports, folate is not likely to have this effect.

Oysters have a very high zinc content; one oyster provides at least the full daily dose of zinc—about 8 to 15 mg. Besides oysters, other types of shellfish, along with poultry and meat (especially organ meats), are high in zinc, providing 1 to 8 mg of zinc per serving. Whole grains, nuts, and seeds provide smaller amounts of zinc, ranging from 0.2 to about 3 mg per serving, and the zinc from them is not as absorbable. Breakfast cereals and nutrition bars are often fortified with substantial amounts of zinc.

Zinc can also be taken as a nutritional supplement in many forms. Zinc citrate, zinc acetate, or zinc picolinate may be the best absorbed, although zinc sulfate is less expensive. People who purchase a supplement should know the difference between the milligrams of actual zinc that the product contains (so-called elemental zinc) and the total milligrams of the zinc product, including the weight of the sulfate, picolinate, and more. All dosages given in this article refer to elemental zinc (unless otherwise stated).

Therapeutic Dosages

For most purposes, zinc should be taken at the recommended daily requirements of 8 to 15 mg. Some evidence suggests that 30 mg of zinc daily may be helpful for acne. For most people, doses up to 40 mg each day are deemed safe for adults and 4 mg per day for children under six months. However, in most studies of zinc for acne, a much higher dose was used: 90 mg daily or more. Doses this high should be used only under physician supervision. Potentially dangerous doses of zinc have also been recommended for sickle cell anemia, macular degeneration, and rheumatoid arthritis.

Zinc supplements should not be taken at the same time as high-fiber foods for best absorption. However, many high-fiber foods provide zinc in themselves. Zinc gluconate may be slightly better absorbed than zinc oxide.

When taking zinc for a long time, taking 1 to 3 mg of copper daily is advisable because zinc supplements can cause copper deficiency. Zinc may also interfere with magnesium and iron absorption.

Zinc is used topically in lozenge or nasal gel form to treat colds. When using zinc this way, the purpose is not to increase zinc levels in the body but to interfere with the action of viruses in the back of the throat or nose. Of the common forms of zinc, only zinc gluconate and zinc acetate have the required antiviral properties. Certain sweeteners and flavorings used in lozenges can block zinc’s antiviral action. Dextrose, sucrose, mannitol, and sorbitol appear to be fine, but citric acid and tartaric acid are not. The information on glycine as a flavoring agent is a bit equivocal.

When using zinc nasal gel products, users should not deeply inhale, as this may cause severe pain. Rather, they should simply squeeze the gel into the nose, according to the directions.

Therapeutic Uses

The use of zinc nasal spray or zinc lozenges at the beginning of a cold may reduce the duration and severity of symptoms, but study results are somewhat inconsistent. These treatments are thought to work by directly interfering with viruses in the nose and throat, and they involve relatively high doses of zinc used for a short time.

Zinc can also be taken long-term at nutritional doses orally to improve overall immunity and reduce the risk of infection. However, this approach is most effective if individuals are deficient in zinc.

A significant body of evidence suggests that oral zinc can reduce symptoms of acne. However, in most studies, potentially toxic doses were used, and the observed benefits were rather slight.

Growing evidence suggests that oral zinc, especially in combination with antioxidants, can help slow the progression of macular degeneration. Oral zinc has also shown promise for sickle cell anemia, attention deficit hyperactivity disorder (ADHD), and stomach ulcers. Zinc has also been shown to be beneficial for acute diarrhea in children, the most convincing evidence coming from studies done in developing countries. This suggests that zinc is most useful for this condition in the presence of a nutritional deficiency. Topical zinc may be helpful for cold sores.

Zinc has shown some promise for treating dysgeusia (impaired taste sensation). In a study of fifty people with idiopathic dysgeusia (impaired taste sensation of no known cause), use of zinc at a rather high dose of 140 mg daily improved taste ability. Another study enrolled seniors with dysgeusia and gave them either placebo or 30 mg of zinc daily; the results were inconclusive. Dysgeusia can also be caused by radiation therapy in the vicinity of the mouth, but overall, the evidence regarding the use of zinc for this purpose is mixed. Kidney dialysis also impairs taste sensation, but once again, zinc supplements failed to prove effective. (The use of any mineral supplement by people undergoing kidney dialysis is potentially dangerous.)

In one study, use of zinc appeared to modestly decrease inflammation of the mucous membranes and skin caused by radiation therapy. Weak, contradictory results have been seen in studies of zinc for anorexia nervosa, depression, rheumatoid arthritis, enhancing sexual function in men on kidney dialysis, tinnitus, and warts.

Some studies have found that persons with human immunodeficiency virus (HIV) infection tend to be deficient in zinc, with levels dropping lower in more severe disease. Higher zinc levels have been linked to better immune function and higher CD4+ cell counts, whereas zinc deficiency has been linked to increased risk of dying from HIV. One preliminary study among people taking azidothymidine (AZT) found that thirty days of zinc supplementation led to decreased rates of opportunistic infection over the following two years. However, other research has linked higher zinc intake to more rapid development of acquired immunodeficiency syndrome (AIDS). Another study failed to find that zinc supplementation reduces diarrhea associated with HIV. People who have HIV should consult their physicians before supplementing with zinc.

Although the evidence that zinc works is not meaningful, the supplement is sometimes recommended for the following conditions: Alzheimer’s disease and minor memory loss in seniors, benign prostatic hyperplasia, bladder infection, cataracts, diabetes, Down syndrome, infertility in men, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), osteoporosis, periodontal disease, prostatitis, psoriasis, and wound and burn healing. An eight-week, double-blind trial of zinc at 67 mg daily failed to find any benefit for eczema symptoms.

Scientific Evidence

Common cold. Lozenges containing zinc gluconate or zinc acetate have shown somewhat inconsistent but generally positive results for reducing the severity and duration of the common cold. For example, in a double-blind trial, one hundred people experiencing the early symptoms of a cold were given a lozenge containing either 13.3 mg of zinc from zinc gluconate or a placebo. Participants took the lozenges several times daily until their cold symptoms subsided. The results were impressive. Coughing disappeared within 2.2 days in the treated group versus four days in the placebo group. Sore throat disappeared after one day versus three days in the placebo group, nasal drainage in four days (versus seven days), and headache in two days (versus three days). Positive results have also been seen in double-blind studies of zinc acetate. While not all studies have been supportive, on balance, results favor the effectiveness of zinc lozenges for treating symptoms of the common cold.

Some research indicates that the exact formulation of zinc lozenges plays a significant role in their effectiveness, and specific flavoring agents, like citric acid and tartaric acid, might prevent zinc from inhibiting viruses. In addition, chemical forms of zinc other than zinc gluconate or zinc acetate might be ineffective, particularly zinc sulfate. Along the same lines, sweeteners, such as sorbitol, sucrose, dextrose, and mannitol, are said to be fine, while glycine has been discussed in an equivocal manner.

The use of zinc in the nose is more controversial. In addition to showing inconsistent results in studies, using zinc nasal gel can cause pain and possibly loss of sense of smell.

For example, in a double-blind, placebo-controlled trial of a widely available zinc nasal gel product, 213 people with a newly starting cold used one squirt of zinc gluconate gel or placebo gel in each nostril every four hours while awake. The results were significant: Treated participants stayed sick an average of 2.3 days, while those receiving placebo were sick for an average of 9 days, a 75 percent reduction in the duration of symptoms. Somewhat more modest but still significant, relative benefits were seen with zinc nasal gel in a double-blind, placebo-controlled study of eighty people with colds. However, another study involving seventy-seven people failed to find benefits, even with near-constant saturation of the nasal passages with zinc gluconate nasal spray. Furthermore, a study of ninety-one people using the standard commercially available nasal spray failed to find benefit. Another double-blind, placebo-controlled trial involving 185 persons failed to find benefits with zinc nasal spray. However, this study used a much lower amount of zinc (fifty times lower) per squirt of spray than was used in the studies just described.

Apart from their direct effect on viruses during an infection, zinc supplements (not lozenges) may play a role in reducing the risk of coming down with a cold in the first place. In a review of two randomized trials, which included 394 healthy children, researchers found that the groups who took zinc had fewer colds, school absences, and prescriptions for antibiotics.

Chronic zinc deficiency is known to weaken the immune system. Although low levels of zinc are uncommon in healthy children and adults living in developed countries, deficiencies may be found among older adults and are widespread among populations in developing countries. A one-year, double-blind study of fifty nursing home residents found that zinc supplements reduced rates of infection compared with placebo. Additionally, in a two-year study of nursing home residents, participants given zinc and selenium developed illnesses less frequently than those given placebo.

Numerous studies in developing countries have also found benefit. For example, a six-month, double-blind, placebo-controlled study of 609 preschool children in India found that zinc supplements reduced the rate of respiratory infections by 45 percent. In addition, more than ten other studies performed in developing countries found that zinc supplements helped prevent respiratory and other infections in children and may reduce symptom severity.

Cold sores. Cold sores are infections caused by the herpes virus. One study suggests that topical zinc may be helpful. In this trial, forty-six individuals with cold sores were treated with a zinc oxide cream or placebo every two hours until cold sores were resolved. The results showed that individuals using the cream experienced a reduced severity of symptoms and a shorter time to full recovery.

Zinc interferes with the ability of the herpes virus to reproduce itself. As with colds, the formulation of zinc must be properly designed to release active zinc ions. This study used a special zinc oxide and glycine formulation. Some participants in this study experienced burning and inflammation caused by the zinc itself, but this seldom caused a serious problem.

Macular degeneration. Macular degeneration is one of the most common causes of vision loss in older adults. A double-blind, placebo-controlled trial evaluated the effects of zinc with or without antioxidants on the progression of macular degeneration in 3,640 individuals in the early stage of the disease. Participants were randomly assigned to receive one of the following: antioxidants (vitamin C 500 mg, vitamin E 400 international units, and beta-carotene 15 mg), or zinc (80 mg) and copper (2 mg), antioxidants plus zinc, or placebo. Copper was administered along with zinc to prevent zinc-induced copper deficiency. The results suggest that zinc alone, or, even better, with antioxidants, significantly slowed the progression of the disease. Previous studies of zinc for macular degeneration found mixed results, but they were much smaller.

There is also evidence that individuals who meet their daily dietary requirements for zinc over many years might reduce their risk of developing macular degeneration later in life. However, the dosages of zinc used in most of these studies are rather high and should be used only under a physician’s supervision.

Attention deficit disorder. Zinc has shown some promise for treating attention deficit hyperactivity disorder (ADHD). In a large (approximately four-hundred-participant), double-blind, placebo-controlled study, 40 mg of daily zinc produced statistically significant benefits compared with placebo among children not using any other treatment. This dose of zinc, while higher than nutritional needs, should be safe. However, the benefits seen were quite modest: About 28 percent of the participants given zinc showed improvement compared with 20 percent in the placebo group.

Another much smaller double-blind, placebo-controlled study evaluated whether zinc at 15 mg per day could enhance the effect of Ritalin. Again, modest benefits were seen. Finally, extremely weak evidence hints that zinc might enhance the effectiveness of evening primrose oil for ADHD.

Acne. Studies suggest that people with acne have lower-than-normal levels of zinc in their bodies. This fact alone does not prove that taking zinc supplements will help acne, but several small double-blind studies involving more than three hundred people have found generally positive results.

In one of these studies, fifty-four people were given a placebo or 135 mg of zinc sulfate daily. Zinc produced slight but measurable benefits. Similar results have been seen in other studies using 90 to 135 mg of zinc daily. Some evidence suggests that a lower and safer 30 mg daily may offer some benefits, including reducing inflammation and oil production and reducing scaring. However, many other studies failed to replicate these results.

Two studies have compared zinc against a standard treatment for acne, the antibiotic tetracycline. One study found that zinc was as effective as tetracycline taken at 250 mg daily, but another found the antibiotic far more effective when taken at 500 mg daily.

Topical zinc treatments for acne typically contain zinc sulfate, zinc acetate, or zinc octoate, while oral forms include zinc salts, zinc gluconate, and zinc sulfate.

The dose of zinc used in most of these studies is rather high, and some people have made themselves extremely ill by taking zinc to treat their acne symptoms. Doses of zinc higher than the recommended safe levels should be used only under a physician’s supervision.

Sickle cell disease. Children with sickle cell disease often do not grow normally. There is some evidence that people with sickle cell disease are more likely to be deficient in zinc. Since zinc deficiency can also cause delayed growth, zinc supplementation at nutritional doses has been suggested for children with sickle cell disease. In a placebo-controlled study, forty-two children (aged four to ten) with sickle cell disease were given 10 mg of zinc daily or placebo for one year. Results showed that the participants given zinc showed enhanced growth compared with those given placebo. Curiously, researchers did not find any solid connection between the severity of zinc deficiency and the extent of response to treatment.

Zinc is thought to stabilize the cell membrane of red blood cells in people with sickle cell disease and has been studied as an aid for preventing sickle cell crisis. In a double-blind, placebo-controlled study of 145 people with sickle cell disease conducted in India, participants received either a placebo or about 50 mg of zinc three times daily. During eighteen months of treatment, the zinc-treated subjects had an average of 2.5 crises, compared with 5.3 for the placebo group. However, zinc did not reduce the severity of a crisis, as measured by the number of days spent in the hospital for each crisis.

Sickle cell disease can also cause skin ulcers (nonhealing sores). In a twelve-week, placebo-controlled trial, using zinc at 88 mg thrice daily for twelve weeks enhanced the ulcer healing rate. However, later studies found zinc did not improve healing in leg ulcers, and scientists concluded the initial results were influenced by researcher bias.

Though research is mixed and further research is needed, zinc has shown positive impacts for individuals with sickle cell disease in aiding growth and development, reducing infection rates, and reducing the risk of vaso-occlusive crisis. While these uses are not confirmed treatments for sickle cell disease, they may help improve some symptoms and complications associated with the disease.

The high dosages of zinc used in some of these studies can cause dangerous toxicity and should be taken (if at all) only under the supervision of a doctor. The nutritional dose described in the first study, however, is safe.

Safety Issues

Zinc taken orally seldom causes any immediate side effects other than occasional stomach upset, usually when taken on an empty stomach. Some forms do have an unpleasant metallic taste. The use of zinc nasal gel, however, has been associated with anosmia (loss of sense of smell). In fact, after receiving more than 130 reports of anosmia, the US Food and Drug Administration (FDA) warned consumers and healthcare providers in 2009 to discontinue certain Zicam Cold Remedy intranasal zinc-containing products, including Zicam Cold Remedy nasal gel, Cold Remedy nasal swabs, and Cold Remedy swabs in children’s size. Furthermore, severe pain may occur if the gel is inhaled too deeply. In 2017, the FDA issued another warning about the products, saying usage could decrease the ability to smell.

Long-term use of oral zinc of 100 mg or more daily can cause toxic effects, including severe copper deficiency, impaired immunity, heart problems, and anemia. Zinc at a dose of more than 50 mg daily might reduce levels of high-density lipoprotein (HDL, or good) cholesterol. In addition, very weak evidence hints that zinc supplements might increase the risk of prostate cancer in men.

The US government has issued recommendations regarding tolerable upper intake levels (ULs, in milligrams, or mg) for zinc. The UL can be thought of as the highest daily intake over a prolonged time known to pose no risks to most members of a healthy population. The ULs for zinc are as follows:

Infants up to six months (4 mg) and seven to twelve months (5 mg); children aged one to three years (7 mg), four to eight years (12 mg), nine to thirteen years (23 mg), and fourteen to eighteen years (34 mg); adults (40 mg); pregnant and nursing girls (34 mg); and pregnant and nursing women (40 mg).

Some interactions occur between zinc and certain medications. For example, zinc can interfere with the absorption of the drug penicillamine (Cuprimine, Depen) used for rheumatoid arthritis. Antibiotics in the tetracycline (Achromycin, Sumycin) or fluoroquinolone (Cipro, Floxin) families also interact with zinc supplements.

The potassium-sparing diuretic amiloride was found to significantly reduce zinc excretion from the body. This means that if people take zinc supplements at the same time as amiloride, zinc accumulation could occur, which could lead to toxic side effects. However, the potassium-sparing diuretic triamterene does not seem to cause this problem.

Important Interactions

People who are using ACE inhibitors, estrogen-replacement therapy, oral contraceptives, thiazide diuretics, or medications that reduce stomach acid (such as H₂ blockers [Zantac] or proton pump inhibitors [Prilosec]) may need to take extra zinc. In addition, the diuretic amiloride could reduce zinc excretion from the body, leading to zinc accumulation, which could cause toxic side effects. People using amiloride should not take zinc supplements unless advised by a physician.

It may be advisable for people taking manganese, calcium, copper, iron, antacids, soy, or antibiotics in the fluoroquinolone (such as Cipro or Floxin) or tetracycline families to separate their doses of zinc and these substances by at least two hours. Zinc also interferes with penicillamine’s absorption, so it may be advisable for people to take zinc and penicillamine at least two hours apart.

Finally, people using zinc supplements should also take extra copper and perhaps magnesium because zinc interferes with their absorption. Zinc interferes with iron absorption, too, but people should not take iron supplements unless they know they are deficient.

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