What is zinc as a therapeutic supplement?

Overview

Zinc is an important element that is found in every cell in the body. More than three hundred enzymes in the body need zinc in order to function properly. Although the amount of zinc needed in the daily diet is tiny, it is very important that individuals get it. However, the evidence suggests that many people do not get enough. Mild zinc deficiency seems to be fairly common, and for this reason, taking a zinc supplement at nutritional doses may be a good idea.

However, taking too much zinc is not a good idea—it can cause toxicity. This article discusses the possible uses of zinc at various doses.

Requirements and Sources

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

Infants aged 0 to 6 months (2 mg) and 7 to 12 months (3 mg); children aged 1 to 3 years (3 mg) and 4 to 8 years (5 mg); boys aged 9 to 13 years (8 mg); males aged 14 years and older (11 mg); females aged 9 to 13 years (8 mg) and 14 to 18 years (9 mg); women (8 mg); pregnant girls (13 mg) and pregnant women (11 mg); and nursing girls (14 mg) and nursing women (12 mg).

The average diet in the developed world may provide insufficient zinc, especially in women, adolescents, infants, and the elderly. Thus, it might be a good idea to increase one’s intake of zinc.

Various drugs may tend to reduce zinc levels in the body by inhibiting its
absorption or increasing its 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 may also inhibit zinc absorption, including calcium, soy, manganese,
copper, and iron. 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 one of 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 be aware of the difference between the milligrams of actual zinc that the product contains (so-called elemental zinc) and the total milligrams of the zinc product, which includes the weight of the sulfate, picolinate, and so forth. All dosages given in this article refer to elemental zinc (unless otherwise stated).

Therapeutic Dosages

For most purposes, zinc should simply 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. This is a safe dose for most people. 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.

For best absorption, zinc supplements should not be taken at the same time as
high-fiber foods. 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, it is advisable to also take 1 to 3 mg of
copper daily 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 for the treatment of 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 in the nose. It appears that 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

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 risk of infection. However, this approach probably works only if individuals are deficient in zinc to begin with.

A significant body of evidence suggests that oral zinc can reduce symptoms of acne. However, in most studies, potentially toxic doses were used, and in any case, the benefits appear to be 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 disorder (ADD), 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 more negative than positive. 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 who were experiencing the early symptoms of
a cold were given a lozenge that contained 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 4 days in the placebo group. Sore
throat disappeared after 1 day versus 3 days in the placebo group, nasal drainage
in 4 days (versus 7 days), and headache in 2 days (versus 3 days). Positive
results have also been seen in double-blind studies of zinc acetate. While not all
studies have been supportive, on balance results appear to favor the effectiveness
of zinc lozenges for treating symptoms of the common cold.

It has been suggested that the exact formulation of the zinc lozenge plays a significant role in its effectiveness. According to this view, certain flavoring agents, such as 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. Zinc sulfate in particular might not work. 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.

Use of zinc in the nose is somewhat more controversial. In addition to showing inconsistent results in studies, use of 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, this one involving seventy-seven people, failed to find benefit 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, this one enrolling 185 persons, failed to find benefit 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 the elderly 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 were helpful for preventing respiratory and other infections in children, and that zinc might 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 reduction in severity of symptoms and a
shorter time to full recovery.

Zinc is thought to interfere 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 the elderly. 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 some evidence that individuals who make sure to get their dietary requirements of zinc on a daily basis over many years might reduce their risk of developing macular degeneration later in life. Keep in mind that 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
treatment of attention deficit disorder (ADD). In a large (approximately
four-hundred-participant), double-blind, placebo-controlled study, use of zinc at
a dose of 40 mg daily 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 ADD.

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 a total of more than three hundred people have found generally positive results.

In one of these studies, fifty-four people were given either placebo or 135 mg of zinc (as 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 dose, 30 mg daily, may offer some benefits. In some studies, however, no benefits were seen.

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.

Keep in mind that the dosages of zinc used in most of these studies are rather high; case reports indicate that people have made themselves extremely ill by taking zinc in the hope of treating 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 than others 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 either zinc supplements (10 mg of zinc daily) or placebo for a
period of one year. Results showed that by the end of the study, 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 have a stabilizing effect on the cell membrane of red blood cells in people with sickle cell disease. For this reason, it has been tried 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 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 seem to 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, use of zinc at 88 mg three times per day for twelve weeks enhanced the rate of ulcer healing.

The high dosages of zinc used in the last two 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 it is taken on an empty stomach. Some forms do have an
unpleasant metallic taste. 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 U.S. Food and Drug Administration (FDA)
warned consumers and health care providers in 2009 to discontinue use of 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, if the gel is inhaled too deeply, severe pain may occur.

Long-term use of oral zinc at dosages of 100 mg or more daily can cause a number of 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 use of zinc supplements might increase risk of prostate cancer in men.

The U.S. 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 aged 0 to 6 months (4 mg) and 7 to 12 months (5 mg); children aged 1 to 3 years (7 mg), 4 to 8 years (12 mg), 9 to 13 years (23 mg), and 14 to 18 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, the use
of zinc can interfere with the absorption of the drug penicillamine
and also with antibiotics in the tetracycline or fluoroquinolone (Cipro, Floxin) families.

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 who are 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.

Bibliography

Bao, B., et al. “Zinc Supplementation Decreases Oxidative Stress, Incidence of Infection, and Generation of Inflammatory Cytokines in Sickle Cell Disease Patients.” Translational Research: The Journal of Laboratory and Clinical Medicine 152 (2008): 67-80.

Carcamo, C., et al. “Randomized Controlled Trial of Zinc Supplementation for Persistent Diarrhea in Adults with HIV-1 Infection.” Journal of Acquired Immune Deficiency Syndromes 43, no. 2 (2006): 197-210.

Ebisch, I. M., et al. “Does Folic Acid and Zinc Sulphate Intervention Affect Endocrine Parameters and Sperm Characteristics in Men?” International Journal of Andrology 29 (2006): 339-345.

Eby, G. A., and W, W. Halcomb. “Ineffectiveness of Zinc Gluconate Nasal Spray and Zinc Orotate Lozenges in Common-Cold Treatment.” Alternate Therapies in Health and Medicine 12 (2006): 34-38.

Halyard, M. Y., et al. Does Zinc Sulfate Prevent Therapy-Induced Taste Alterations in Head and Neck Cancer Patients? Results of Phase III Double-Blind, Placebo-Controlled Trial from the North Central Cancer Treatment Group (N01C4).” International Journal of Radiation Oncology, Biology, Physics 67 (2007): 1318-1322.

Kurugol, Z., N. Bayram, and T. Atik. “Effect of Zinc Sulfate on Common Cold in Children.” Pediatrics International: Official Journal of the Japan Pediatric Society 49 (2007): 842-847.

Lazzerini, M., and L. Ronfani. “Oral Zinc for Treating Diarrhoea in Children.” Cochrane Database of Systematic Reviews 3 (2008): CD005436.

Lin, L. C., et al. “Zinc Supplementation to Improve Mucositis and Dermatitis in Patients After Radiotherapy for Head-and-Neck Cancers.” International Journal of Radiation Oncology, Biology, Physics 65 (2006): 745-750.

Maylor, E. A., et al. “Effects of Zinc Supplementation on Cognitive Function in Healthy Middle-Aged and Older Adults.” British Journal of Nutrition 96 (2006): 752-760.

Patro, B., D. Golicki, and H. Szajewska. “Meta-analysis: Zinc Supplementation for Acute Gastroenteritis in Children.” Alimentary Pharmacology and Therapeutics 28, no. 6 (2008): 713-723.

Prasad, A. S., et al. “Zinc Supplementation Decreases Incidence of Infections in the Elderly: Effect of Zinc on Generation of Cytokines and Oxidative Stress.” American Journal of Clinical Nutrition 85 (2007): 837-844.

Singh, M., and R. R. Das. “Zinc for the Common Cold.” Cochrane Database of Systematic Reviews 2 (2011): CD001364.