|
Zinc
Introduction
Zinc is an important element that is found in every cell
in the body. More than 300 enzymes in the body need zinc in order to
function properly. Although the amount of zinc we need in our daily diet
is tiny, it's very important that we get it. However, the evidence
suggests that many of us do not get enough. Mild zinc deficiency
seems to be fairly common.
Severe zinc deficiency can cause a major loss of immune
function, and mild zinc deficiency might impair immunity slightly. For
this reason, making sure to get enough zinc may help keep you from
catching colds or other infections. But zinc may be helpful for colds in
a completely different way, too, by directly interfering with viruses in
the nose or throat. For this purpose, it is used either as a nasal spray
or in the form of lozenges taken every 2 hours from the first sign of
cold symptoms.
Intriguing evidence suggests that zinc supplements may
have other specific benefits as well, including helping stomach ulcers
heal, relieving symptoms of rheumatoid arthritis, slightly improving
acne symptoms, increasing sperm count, aiding recovery from anorexia
nervosa, improving growth rate in children with sickle-cell disease, and
preventing "sickle-cell crisis" (a serious condition in people with
sickle-cell anemia).
Requirements/Sources
The official U.S. recommendations for daily intake of
zinc are as follows:
- Infants 0-6 months, 2 mg
7-12 months, 3 mg
- Children 1-3 years, 3 mg
4-8 years, 5 mg
- Males 9-13 years, 8 mg
14 years and older 11 mg
- Females 9-13 years, 8 mg
14-18 years, 9 mg
19 years and older, 8 mg
- Pregnant women, 11 mg (13 mg if 18 years old or
younger)
- Nursing women, 12 mg (14 mg if 18 years old or
younger)
The average diet in the developed world commonly provides
insufficient zinc, especially in women, adolescents, infants, and the
elderly.1-5 Thus, it may be a wise idea to increase your
intake of zinc on general principles.
Individuals with alcoholism, sickle-cell anemia,
diabetes, or kidney disease are also thought to be at increased risk for
zinc deficiency.
Various drugs may also inhibit zinc absorption, including
captopril and possibly other ACE inhibitors, drugs which reduce stomach
acid (including H2 blockers and proton pump inhibitors), and
oral contraceptives.6-12 Certain nutrients may have the same
effect, such as calcium, soy, manganese, copper, and iron.13-29
Contrary to previous reports, folate is not likely to significantly
affect zinc absorption.30
Thiazide diuretics ("water pills") can cause excessive
loss of zinc in the urine.31,32
Oysters are by far the best food source of zinca single
serving will give you about 10 times the recommended daily
intake! Seeds and nuts, peas, whole wheat, rye, and oats are not nearly
as high in zinc, but you can get about 3 mg per serving of these foods.
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. When you
purchase a supplement, you should be aware of the difference between the
milligrams of actual zinc the product contains (so-called elemental
zinc) and the total milligrams of the zinc product. All figures given in
this article refer to the amount of actual zinc to take.
Therapeutic Dosages
For most purposes, zinc should simply be taken at the
recommended daily requirements listed previously. For best absorption,
zinc supplements should not be taken at the same time as high-fiber
foods;33,34 however, many high-fiber foods provide zinc in
themselves.
When taking zinc long term it is advisable to take 1 to 3
mg of copper daily as well, because zinc supplements can cause copper
deficiency.35,36 Zinc may also interfere with magnesium37
and iron38 absorption.
For treatment of colds, much higher doses of zinc are
used, although only for a short period of time. The usual dosage is 13
to 23 mg of zinc as zinc gluconate every 2 hours for a week or two (but
no longer). The purpose is not to increase zinc levels in your body, but
to interfere with the action of viruses in the back of your throat (or,
in the case of zinc nasal spray, in the nose). It appears that of the
common forms of zinc, only zinc gluconate and zinc acetate have the
required antiviral properties.39,40 Also, some 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.
Long-term use of relatively high-dose zinc (90 mg daily
or more) has been tried for various conditions such as acne, sickle-cell
anemia, and rheumatoid arthritis, but medical supervision is essential
because of the risk of toxicity (see Safety Issues).
Therapeutic Uses
Good evidence suggests that if you take zinc lozenges
every 2 hours at the beginning of a cold, you will recover much more
quickly.41 One study suggests that zinc nasal spray may be
even more effective.42 These methods supply a high dose of
zinc for a short time, and are thought to work by directly interfering
with viruses in the nose and throat. Zinc can also be taken at
nutritional doses orally to improve immunity;43,44 however,
this approach probably only works if you are deficient in zinc to begin
with.
Topical zinc may also be helpful for cold sores.45
Pregnant women should make sure to get enough zinc. One
large double-blind study in zinc-deficient pregnant women found that a
standard zinc supplement could significantly improve the birth weight
and head size of their newborn children.46 However, zinc
supplements failed to make any difference in another large double-blind
study of pregnant women that did not specifically select zinc-deficient
women.47
Evidence also suggests that zinc can reduce symptoms of
acne,48-53 although most studies used high, possibly toxic,
doses of zinc.
Growing evidence suggests that zinc, especially in
combination with antioxidants, can help slow the progression of macular
degeneration.105,106,156
Zinc may also improve growth rate in children with sickle
cell anemia161 and help prevent the development of
sickle-cell crisis.54 Zinc might also speed the healing of
stomach ulcers.55,56
Zinc has been tested as a treatment for rheumatoid
arthritis with mixed results;57-62,159,160 overall, the
evidence is not encouraging.
Some, but not all, studies have found that HIV-positive
individuals tend to be deficient in zinc, with levels dropping lower in
more severe disease.64-69 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.70,71,72
One preliminary study among people taking AZT found that 30 days of zinc
supplementation led to decreased rates of opportunistic infection over
the following 2 years.73 However, other research has linked
higher zinc intake to more rapid development of AIDS.74,75
The bottom line: If you have HIV, consult your physician before
supplementing with zinc.
Preliminary evidence from two small, double-blind trials
suggests that zinc supplements might be helpful in treating anorexia
nervosa, possibly enhancing weight gain and helping stabilize mood.81,82,162
One frequently quoted study often used to discredit the use of zinc in
anorexia appears to be relatively meaningless when inspected closely.83,162
One small uncontrolled study found that zinc supplements
increased sperm counts and improved fertility for men with low
testosterone levels.76 But no such effect was seen in men
whose testosterone levels were normal to begin with.
Although the evidence that it works is not yet
meaningful, zinc is sometimes recommended for the following conditions
as well: Alzheimer's disease,77-80attention deficit disorder,
benign prostatic hyperplasia,87-93bladder infection,
cataracts, diabetes,94,95,96 Down's syndrome,97,98,99impotence,100
inflammatory bowel disease (ulcerative colitis and Crohn's disease),101-104osteoporosis,107periodontal
disease, prostatitis,108psoriasis, tinnitus,109,110
and wound and burn healing.111,112,113
An 8-week double-blind trial of zinc at the somewhat high
dose of 67 mg daily failed to find any benefit for eczema symptoms.158
What Is the Scientific Evidence for Zinc?
Colds
Numerous studies have evaluated the effects of zinc
lozenges or zinc nasal spray for colds. Most found positive results, as
long as the right form of zinc is used (zinc gluconate or acetate).
In a double-blind placebo-controlled trial, 213
individuals with a newly starting cold used one squirt of zinc gluconate
gel or placebo gel in each nostril every 4 hours while awake.114
The results were dramatic: Treated participants stayed sick an average
of 2.3 days, while those receiving placebo were sick for an average of 9
days, a whopping 75% reduction in the duration of symptoms.
A more recent study found no benefits with zinc nasal
spray. In this double-blind placebo-controlled trial, 185 individuals
who had just started to develop cold symptoms were given either a zinc
spray or placebo.115 No benefits were seen in the treated
group as compared to the placebo group. However, this study used a much
lower amount of zinc per squirt of spray than that of the positive
study: 50 times lower to be exact. In addition, the spray contained zinc
sulfate rather than zinc gluconate. The exact chemical form of zinc
appears to markedly influence its ability to kill cold viruses (see
below).
Zinc lozenges also appear to be helpful. For example, in
a double-blind trial, 100 people who were experiencing the early
symptoms of a cold were given a lozenge that either contained 13.3 mg of
zinc from zinc gluconate or was just a placebo.116
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.117,118
Not all studies have shown such positive results.119
However, the overall results appear to be favorable.120 It
has been suggested that the exact formulation of the zinc lozenge plays
a significant role. Flavoring agents, such as citric acid and tartaric
acid, appear to prevent zinc from inhibiting viruses, and chemical forms
of zinc other than zinc gluconate or zinc acetate may not work.121
Sweeteners such as sorbitol, sucrose, dextrose, and mannitol are fine,
but the information on glycine as a flavoring agent is equivocal.
Besides using zinc to directly interfere with viruses,
supplementation at nutritional dosages may also help reduce the
frequency of colds by strengthening your overall health.
In a 2-year study of nursing home residents, participants
given zinc and selenium developed illnesses much less frequently than
those given placebo.122 Of course, it isn't clear from this
study which was more helpful, the zinc or the selenium. However, we do
know that chronic zinc deficiency weakens the immune system,123
and studies performed in developing countries using zinc alone have
found benefits. For example, a 6-month double-blind placebo-controlled
study of 609 preschool children in India found that zinc
supplementsreduced the rate of respiratory infections by 45%.124
Nine other studies have also found zinc supplements helpful for
preventing illness.125
Cold Sores
Cold sores are infections caused by the herpes virus. One
study suggests that topical zinc may be helpful. In this trial, 46
individuals with cold sores were treated with a zinc oxide cream or
placebo every 2 hours until cold sores resolved.126 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.
Acne
Studies suggest that people with acne have
lower-than-normal levels of zinc in their bodies.127,128,129
This fact alone does not prove that taking zinc supplements will help
acne, but several small double-blind studies involving a total of over
300 people have found generally positive results.
In one of these studies, 54 people were given either
placebo or 135 mg of zinc as zinc sulfate daily. Zinc produced slight
but measurable benefits.130 Similar results have been seen in
other studies using 90 to 135 mg of zinc daily.131-134 One
study suggests that a lower and safer dose, 30 mg daily, may also be
helpful.135 In some studies, however, no benefits were seen.136,137
Two studies have compared zinc against a standard
treatment for acne, the antibiotic tetracycline. One found that zinc was
as effective as tetracycline taken at 250 mg daily,138 but
another found the antibiotic far more effective when taken at 500 mg
daily.139
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.
Sickle-Cell Anemia
Children with sickle cell disease often do not grow
normally. In a placebo-controlled study, 42 children with sickle cell
disease (age 4 to 10) were given either zinc supplements (10 mg zinc
daily) or placebo for a period of 1 year.161 Results showed
that by the end of the study, the participants given zinc showed
enhanced growth compared to those given placebo. It is not clear whether
participants were actually deficient in zinc or simply benefited from
the zinc supplement regardless of deficiency.
Unfortunately, (and inexplicably) this study does not
appear to have been double-blind, which makes the results less than
fully reliable.
Zinc may also be helpful in preventing "sickle-cell
crisis" in individuals with sickle-cell anemia.140 A
double-blind placebo-controlled study treated 145 sickle-cell subjects
with either 220 mg of zinc sulfate 3 times daily or placebo. During 18
months of treatment, the zinc-treated subjects had an average of 2.5
crises, compared to 5.3 for the placebo group. However, zinc didn't seem
to reduce the severity of a crisis, as measured by the number of days
spent in the hospital for each crisis.
Warning: Sickle-cell anemia is far too serious a
condition to self-treat, and the relatively high dosages of zinc used in
this study should be taken only under the supervision of a doctor (see
Safety Issues).
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.156 Participants were randomly assigned to receive
one of the following: antioxidants (vitamin C 500 mg, vitamin E 400 IU,
and beta-carotene 15 mg), 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.141,142
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.
In addition, there is some evidence that making sure to
get your dietary requirement of zinc on a daily basis over many years
might reduce the risk of developing macular degeneration later in life.143
 Safety
Issues
Zinc seldom causes any immediate side effects other than
occasional stomach upset, usually when it's taken on an empty stomach.
Some forms do have an unpleasant metallic taste.
However, long-term use of 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.144-147
The U.S. government has issued recommendations regarding "tolerable
upper intake levels" (ULs) 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:157
- Infants 0-6 months, 4 mg
7-12 months, 5 mg
- Children 1 to 3 years, 7 mg
4 to 8 years, 12 mg
9 to 13 years, 23 mg
- Males and females 14 to 18 years, 34 mg
19 years and older, 40 mg
- Pregnant or nursing women, 40 mg (34 mg if 18 years
old or younger)
Use of zinc can interfere with the absorption of
penicillamine antibiotics in the tetracycline or fluoroquinolone (Cipro,
Floxin) families.148-153
The potassium-sparing diuretic amiloride was found to
significantly reduce zinc excretion from the body.154 This
means that if you take zinc supplements at the same time as amiloride,
zinc accumulation could occur. This could lead to toxic side effects.
However, the potassium-sparing diuretic triamterene does not seem to
cause this problem.155
Interactions You Should Know About
If you are taking
- Medications that reduce stomach acid such as Zantac
(ranitidine) or Prilosec (omeprazole); ACE inhibitors; oral
contraceptives; estrogen-replacement therapy; thiazide diuretics;
calcium; copper; or iron: You may need to take extra zinc.
- Manganese, antacids, soy, or antibiotics in the
fluoroquinolone (e.g., Cipro, Floxin) or tetracycline families: It may
be advisable to separate your doses of zinc and these substances by at
least 2 hours.
- Zinc supplements: You should also take extra
copper, and perhaps magnesium as well because zinc interferes with
their absorption. Zinc interferes with iron absorption, too, but you
shouldn't take iron supplements unless you know you are deficient.
- Penicillamine: Zinc interferes with penicillamine's
absorption so it may be advisable to take zinc and penicillamine at
least 2 hours apart.
- Amiloride: It could reduce zinc excretion from the
body, leading to zinc accumulation, which could cause toxic side
effects. Do not take zinc supplements unless advised by a physician.
References
1. Sandstead HH. Zinc nutrition in the
United States. Am J Clin Nutr. 1973;26:1251-1260.
2. Prasad AS. Role of zinc in human
health. Bol Asoc Med PR. 1991;83:558-560.
3. Prasad AS. Zinc deficiency in women,
infants, and children. J Am Coll Nutr. 1996;15:113-120.
4. Goldenberg RL, Tamura T, Neggers Y, et
al. The effect of zinc supplementation on pregnancy outcome. JAMA.
1995;274:463-468.
5. Stang J, Story MT, Harnack L, et al.
Relationships between vitamin and mineral supplement use, dietary
intake, and dietary adequacy among adolescents. J Am Diet Assoc.
2000;100:905-910.
6. Baum MK, Javier JJ, Mantero-Atienza E,
et al. Zidovudine-associated adverse reactions in a longitudinal study
of asymptomatic HIV-1-infected homosexual males. J Acquir Immune
Defic Syndr. 1991;4:1218-1226.
7. Golik A, Modai D, Averbukh Z, et al.
Zinc metabolism in patients treated with captopril versus enalapril.
Metabolism. 1990;39:665-667.
8. Golik A, Zaidenstein R, Dishi V, et al.
Effects of captopril and enalapril on zinc metabolism in hypertensive
patients. J Am Coll Nutr. 1998;17:75-78.
9. Sturniolo GC, Montino MC, Rossetto L,
et al. Inhibition of gastric acid secretion reduces zinc absorption in
man. J Am Coll Nutr. 1991;10:372-375.
10. Reyes AJ, Olhaberry JV, Leary WP, et
al. Urinary zinc excretion, diuretics, zinc deficiency and some
side-effects of diuretics. S Afr Med J. 1983;64:936-941.
11. Reyes AJ, Leary WP, Lockett CJ, et al.
Diuretics and zinc. S Afr Med J. 1982;62:373-375.
12. Webb JL. Nutritional effects of oral
contraceptive use: a review. J Reprod Med. 1980;25:150-156.
13. Argiratos V, Samman S. The effect of
calcium carbonate and calcium citrate on the absorption of zinc in
healthy female subjects. Eur J Clin Nutr. 1994;48:198-204.
14. Spencer H, Kramer L, Norris C, et al.
Effect of calcium and phosphorus on zinc metabolism in man. Am J Clin
Nutr. 1984;40:1213-1218.
15. Dawson-Hughes B, Seligson FH, Hughes
VA. Effects of calcium carbonate and hydroxyapatite on zinc and iron
retention in postmenopausal women. Am J Clin Nutr. 1986;44:83-88.
16. Spencer H, Norris C, Osis D. Further
studies of the effect of zinc on intestinal absorption of calcium in
man. J Am Coll Nutr. 1992;11:561-566.
17. Crowther RS, Marriott C. Counter-ion
binding to mucus glycoproteins. J Pharm Pharmacol. 1984;36:21-26.
18. Hwang S-J, Lai YH, Chen HC, et al.
Comparisons of the effects of calcium carbonate and calcium acetate on
zinc tolerance test in hemodialysis patients. Am J Kidney Dis.
1992;19:57-60.
19. Pecoud A, Donzel P, Schelling JL.
Effect of foodstuffs on the absorption of zinc sulfate. Clin
Pharmacol Ther. 1975;17:469-474.
20. Navert B, Sandstrom B, Cederblad A.
Reduction of the phytate content of bran by leavening in bread and its
effect on zinc absorption in man. Br J Nutr. 1985;53:47-53.
21. Vohra P, Gray GA, Kratzer FH. Phytic
acid-metal complexes. Proc Soc Exp Biol Med. 1965;120:447-449.
22. Sandstrom B, Davidsson L, Cederblad A,
et al. Oral iron, dietary ligands and zinc absorption. J Nutr.
1985;115:411-414.
23. Meadows NJ, Grainger SL, Ruse W, et
al. Oral iron and the bioavailability of zinc. Br Med J (Clin Res
Ed). 1983;287:1013-1014.
24. Solomons NW, Jacob RA. Studies on the
bioavailability of zinc in humans: effects of heme and nonheme iron on
the absorption of zinc. Am J Clin Nutr. 1981;34:475-482.
25. Davidsson L, Almgren A, Sandstrom B,
et al. Zinc absorption in adult humans: the effect of iron
fortification. Br J Nutr. 1995;74:417-425.
26. Newhouse IJ, Clement DB, Lai C.
Effects of iron supplementation and discontinuation on serum copper,
zinc, calcium, and magnesium levels in women. Med Sci Sports Exerc.
1993;25:562-571.
27. Aggett PJ, Crofton RW, Khin C, et al.
The mutual inhibitory effects on their bioavailability of inorganic zinc
and iron. Prog Clin Biol Res. 1983;129:117-124.
28. Scott KC, Turnlund JR. A compartmental
model of zinc metabolism in adult men used to study effects of three
levels of dietary copper. Am J Physiol. 1994;267: E165-E173.
29. Freeland-Graves JH. Manganese: an
essential nutrient for humans. Nutr Today. 1988;23:13-19.
30. Butterworth CE Jr, Tamura T. Folic
acid safety and toxicity: a brief review. Am J Clin Nutr.
1989;50:353-358.
31. Reyes AJ, Leary WP, Lockett CJ, et al.
Diuretics and zinc. S Afr Med J. 1982;62:373-375.
32. Reyes AJ, Olhaberry JV, Leary WP, et
al. Urinary zinc excretion, diuretics, zinc deficiency and some
side-effects of diuretics. S Afr Med J. 1983;64:936-941.
33. Navert B, Sandstrom B, Cederblad A.
Reduction of the phytate content of bran by leavening in bread and its
effect on zinc absorption in man. Br J Nutr. 1985;53:47-53.
34. Vohra P, Gray GA, Kratzer FH. Phytic
acid-metal complexes. Proc Soc Exp Biol Med. 1965;120:447-449.
35. Hoffman HN II, Phyliky RL, Fleming CR.
Zinc-induced copper deficiency. Gastroenterology.
1988;94:508-512.
36. Sandstead HH. Requirements and
toxicity of essential trace elements, illustrated by zinc and copper.
Am J Clin Nutr. 1995;61(suppl 3):621S-624S.
37. Spencer H, Norris C, Williams D.
Inhibitory effects of zinc on magnesium balance and magnesium absorption
in man. J Am Coll Nutr. 1994;13:479-484.
38. Yadrick MK, Kenney MA, Winterfeldt EA.
Iron, copper, and zinc status: Response to supplementation with zinc or
zinc and iron in adult females. Am J Clin Nutr. 1989;49:145-150.
39. Marshall S. Zinc gluconate and the
common cold. Review of randomized controlled trials. Can Fam
Physician. 1998;44:1037-1042.
40. Eby GA. Zinc ion availabilitythe
determinant of efficacy in zinc lozenge treatment of common colds. J
Antimicrob Chemother. 1997;40:483-493.
41. Marshall S. Zinc gluconate and the
common cold. Review of randomized controlled trials. Can Fam
Physician. 1998;44:1037-1042.
42. Hirt M, Nobel S, Barron E. Zinc nasal
gel for the treatment of common cold symptoms: a double-blind,
placebo-controlled trial. Ear Nose Throat J. 2000;79:778-781.
43. Girodon F, Lombard M, Galan P, et al.
Effect of micronutrient supplementation on infection in
institutionalized elderly subjects: a controlled trial. Ann Nutr
Metab. 1997;41:98-107.
44. Bhutta ZA, Black RE, Brown KH, et al.
Prevention of diarrhea and pneumonia by zinc supplementation in children
in developing countries: Pooled analysis of randomized controlled
trials. J Pediatr. 1999;135:689-697.
45. Godfrey HR, Godfrey NJ, Godfrey JC, et
al. A randomized clinical trial on the treatment of oral herpes with
topical zinc oxide/glycine. Altern Ther Health Med. 2001;7:49-54,
56.
46. Goldenberg RL, Tamura T, Neggers Y, et
al. The effect of zinc supplementation on pregnancy outcome. JAMA.
1995;274:463-468.
47. Jonsson B, Hauge B, Larsen MF, et al.
Zinc supplementation during pregnancy: a double blind randomised
controlled trial. Acta Obstet Gynecol Scand. 1996;75:725-729.
48. Dreno B, Amblard P, Agache P, et al.
Low doses of zinc gluconate for inflammatory acne. Acta Derm Venereol.
1989;69:541-543.
49. Goransson K, Liden S, Odsell L. Oral
zinc in acne vulgaris: a clinical and methodological study. Acta Derm
Venereol. 1978;58:443-448.
50. Verma KC, Saini AS, Dhamija SK. Oral
zinc sulfate therapy in acne vulgaris: a double-blind trial. Acta
Derm Venereol. 1980;60:337-340.
51. Weimar VM, Puhl SC, Smith WH, et al.
Zinc sulfate in acne vulgaris. Arch Dermatol. 1978;114:1776-1778.
52. Hillstrom L, Pettersson L, Hellbe L,
et al. Comparison of oral treatment with zinc sulphate and placebo in
acne vulgaris. Br J Dermatol. 1977;97:681-684.
53. Michaelsson G, Juhlin L, Vahlquist A.
Effects of oral zinc and vitamin A in acne. Arch Dermatol.
1977;113:31-36.
54. Gupta VL, Chaubey BS. Efficacy of zinc
therapy in prevention of crisis in sickle-cell anemia: a double-blind,
randomized controlled clinical trial. J Assoc Physicians India.
1995;43:467-469.
55. Frommer DJ. The healing of gastric
ulcers by zinc sulphate. Med J Aust. 1975;2:793-796.
56. Garcia-Plaza A, Arenas JI, Belda O, et
al. A multicenter clinical trial. Zinc acexamate versus famotidine in
the treatment of acute duodenal ulcer [in Spanish; English abstract].
Rev Esp Enferm Dig. 1996;88:757-762.
57. Simkin PA. Treatment of rheumatoid
arthritis with oral zinc sulfate. Agents Actions Suppl.
1981;8:587-596.
58. Pandey SP, Bhattacharya SK, Sundar S.
Zinc in rheumatoid arthritis. Indian J Med Res. 1985;81:618-620.
59. Mattingly PC, Mowat AG. Zinc sulphate
in rheumatoid arthritis. Ann Rheum Dis. 1982;41:456-457.
60. Rasker JJ, Kardaun SH. Lack of
beneficial effect of zinc sulphate in rheumatoid arthritis. Scand J
Rheumatol. 1982;11:168 -170.
61. Dixon JS, Bird HA, Martin MF, et al.
Biochemical and clinical changes occurring during the treatment of
rheumatoid arthritis with novel antirheumatoid drugs. Int J Clin
Pharmacol Res. 1985;5:25-33.
62. Job C, Menkes CJ, Delbarre F. Zinc
sulphate in the treatment of rheumatoid arthritis. Arthritis Rheum.
1980;23:1408-1409.
63. Simkin PA. Treatment of rheumatoid
arthritis with oral zinc sulfate. Agents Actions Suppl.
1981;8:587-596.
64. Fabris N, Mocchegiani E, Galli M, et
al. AIDS, zinc deficiency, and thymic hormone failure [letter]. JAMA.
1988;259:839-840.
65. Sappey C, Leclercq P, Coudray C, et
al. Vitamin, trace element and peroxide status in HIV seropositive
patients: asymptomatic patients present a severe beta-carotene
deficiency. Clin Chim Acta. 1994;230:35-42.
66. Odeh M. The role of zinc in acquired
immunodeficiency syndrome. JIntern Med. 1992;231:463-469.
67. Periquet BA, Jammes NM, Lambert WE, et
al. Micronutrient levels in HIV-1-infected children. AIDS.
1995;9:887-893.
68. Tomaka FL, Imoch PJ, Reiter WM, et al.
Prevalence of nutritional deficiencies in patients with HIV Infection
[abstract]. Int Conf AIDS. 1994;10:221.
69. Baum MK, Shor-Posner G, Lu Y, et al.
Micronutrients and HIV-1 disease progression. AIDS.
1995;9:1051-1056.
70. Campa A, Lai H, Shor-Posner G, et al.
Relationship between zinc deficiency and survival in HIV+ homosexual men
[abstract]. FASEB J. 1998;12:A217.
71. Baum MK, Shor-Posner G, Lu Y, et al.
Micronutrients and HIV-1 disease progression. AIDS.
1995;9:1051-1056.
72. Bogden JD, Kemp FW, Han S, et al.
Status of selected nutrients and progression of human immunodeficiency
virus type 1 infection. Am J Clin Nutr. 2000;72:809-815.
73. Mocchegiani E, Rivabene R, Santini MT.
Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT)
therapy against opportunistic infections in AIDS. Int
JImmunopharmacol. 1995;17:719-727.
74. Tang AM, Graham NHM, Kirby AJ, et al.
Dietary micronutrient intake and risk of progression to acquired
immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1
(HIV-1)-infected homosexual men. Am JEpidemiol. 1993;138:937-951.
75. Tang AM, Graham NM, Saah AJ. Effects
of micronutrient intake on survival in human immunodeficiency virus type
1 infection. Am JEpidemiol. 1996;143:1244-1256.
76. Netter A, Hartoma R, Nahoul K. Effect
of zinc administration on plasma testosterone, dihydrotestosterone, and
sperm count. Arch Androl. 1981;7:69-73.
77. Constantinidis J. Alzheimer's disease:
the zinc theory [in French; English abstract]. Encephale.
1990;16:231-239.
78. Constantinidis J. The hypothesis of
zinc deficiency in the pathogenesis of neurofibrillary tangles. Med
Hypotheses. 1991;35:319-323.
79. Cuajungco MP, Lees GJ. Zinc metabolism
in the brain: Relevance to human neurodegenerative disorders.
Neurobiol Dis. 1997;4:137-169.
80. Lovell MA, Robertson JD, Teesdale WJ,
et al. Copper, iron and zinc in Alzheimer's disease senile plaques. J
Neurol Sci. 1998;158:47-52.
81. Birmingham CL, Goldner EM, Bakan R.
Controlled trial of zinc supplementation in anorexia nervosa. Int J
Eat Disord. 1994;15:251-255.
82. Katz RL, Keen CL, Litt IF, et al. Zinc
deficiency in anorexia nervosa. J Adolesc Health Care.
1987;8:400-406.
83. Lask B, Fosson A, Rolfe U, et al. Zinc
deficiency and childhood-onset anorexia nervosa. J Clin Psychiatry.
1993;54:63-66.
84. Roijen SB, Worsaae U, Zlotnik G. Zinc
in patients with anorexia nervosa [in Danish; English abstract].
Ugeskr Laeger. 1991;153:721-723.
85. Ward NI. Assessment of zinc status and
oral supplementation in anorexia nervosa. J Nutr Med.
1990;1:171-177.
86. Castillo-Duran C, Heresi G, Fisberg M,
et al. Controlled trial of zinc supplementation during recovery from
malnutrition: effects on growth and immune function. Am J Clin Nutr.
1987;45:602-608.
87. Bandlish U, Prabhakar BR, Wadehra PL.
Plasma zinc level estimation in enlarged prostate. Indian J Pathol
Microbiol. 1988;31:231-234.
88. Gonick P, Oberleas D, Knechtges T, et
al. Atomic absorption spectrophotometric determination of zinc in the
prostate. Invest Urol. 1969;6:345-347.
89. Schrodt GR, Hall T, Whitmore WF. The
concentration of zinc in diseased human prostate glands. Cancer.
1964;17:1555-1566.
90. Gyorkey F, Min KW, Huff JA, et al.
Zinc and magnesium in human prostate gland: normal, hyperplastic and
neoplastic. Cancer Res. 1967;27:1348-1353.
91. Gyorkey F, Sato CS. In vitro
65Zn-binding capacities of normal, hyperplastic, and carcinomatous human
prostate gland. Exp Mol Pathol. 1968;8:216-224.
92. Leake A, Chisholm GD, Habib FK. The
effect of zinc on the 5 alpha-reduction of testosterone by the
hyperplastic human prostate gland. J Steroid Biochem.
1984;20:651-655.
93. Leake A, Chrisholm GD, Busuttil A, et
al. Subcellular distribution of zinc in the benign and malignant human
prostate: evidence for a direct zinc androgen interaction. Acta
Endocrinol (Copenh). 1984;105:281-288.
94. Schmidt LE, Arfken CL, Heins JM.
Evaluation of nutrient intake in subjects with non-insulin-dependent
diabetes mellitus. J Am Diet Assoc. 1994;94:773-774.
95. Blostein-Fujii A, DiSilvestro RA, Frid
D, et al. Short-term zinc supplementation in women with
non-insulin-dependent diabetes mellitus: effects on plasma
5'-nucleotidase activities, insulin-like growth factor I concentrations,
and lipoprotein oxidation rates in vitro. Am J Clin Nutr.
1997;66:639-642.
96. Rauscher AM, Fairweather-Tait SJ,
Wilson PD, et al. Zinc metabolism in non-insulin dependent diabetes
mellitus. J Trace Elem Med Biol. 1997;11:65-70.
97. Sustrova M, Strbak V. Thyroid function
and plasma immunoglobulins in subjects with Down's syndrome (DS) during
ontogenesis and zinc therapy. J Endocrinol Invest.
1994;17:385-390.
98. Licastro F, Mocchegiani E, Masi M, et
al. Modulation of the neuroendocrine system and immune functions by zinc
supplementation in children with Down's syndrome. J Trace Elem
Electrolytes Health Dis. 1993;7:237-239.
99. Lockitch G, Puterman M, Godolphin W,
et al. Infection and immunity in Down syndrome: a trial of long-term low
oral doses of zinc. J Pediatr. 1989;114:781-787.
100. Rodger RS, Sheldon WL, Watson MJ, et
al. Zinc deficiency and hyperprolactinaemia are not reversible causes of
sexual dysfunction in uraemia. Nephrol Dial Transplant.
1989;4:888-892.
101. Sjogren A, Floren CH, Nilsson A.
Evaluation of zinc status in subjects with Crohn's disease. J Am Coll
Nutr. 1988;7:57-60.
102. Van de Wal Y, Van der Sluys Veer A,
Verspaget HW, et al. Effect of zinc therapy on natural killer cell
activity in inflammatory bowel disease. Aliment Pharmacol Ther.
1993;7:281-286.
103. Mulder TP, van der Sluys Veer A,
Verspaget HW, et al. Effect of oral zinc supplementation on
metallothionein and superoxide dismutase concentrations in patients with
inflammatory bowel disease. J Gastroenterol Hepatol.
1994;9:472-477.
104. Dronfield MW, Malone JD, Langman MJ.
Zinc in ulcerative colitis: a therapeutic trial and report on plasma
levels. Gut.1977;18:33-36.
105. Stur M, Tittl M, Reitner A, et al.
Oral zinc and the second eye in age-related macular degeneration.
Invest Ophthalmol Vis Sci. 1996;37:1225-1235.
106. Newsome DA, Swartz M, Leone NC, et
al. Oral zinc in macular degeneration. Arch Ophthalmol.
1988;106:192-198.
107. Relea P, Revilla M, Ripoll E, et al.
Zinc, biochemical markers of nutrition, and type-I osteoporosis. Age
Ageing. 1995;24:303-307.
108. Neal DE Jr, Kaack MB, Fussell EN, et
al. Changes in seminal fluid zinc during experimental prostatitis.
Urol Res. 1993;21:71-74.
109. Gersdorff M, Robillard T, Stein F, et
al. The zinc sulfate overload test in patients suffering from tinnitus
associated with low serum zinc. Preliminary report [in French; English
abstract]. Acta Otorhinolaryngol Belg. 1987;41:498-505.
110. Paaske PB, Pederson CB, Kjems G, et
al. Zinc therapy of tinnitus. A placebo-controlled study [in Danish;
English abstract]. Ugeskr Laeger. 1990;152:2473-2475.
111. Han CM. Changes in body zinc and
copper levels in severely burned patients and the effects of oral
administration of ZnS04 by a double-blind method [in Chinese; English
abstract]. Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi.
1990;6:83-86, 155.
112. Agren MS, Stromberg HE, Rindby A, et
al. Selenium, zinc, iron and copper levels in serum of patients with
arterial and venous leg ulcers. Acta Derm Venereol.
1986;66:237-240.
113. Floersheim GL, Lais E. Lack of effect
of oral zinc sulfate on wound healing in leg ulcer [in German; English
abstract]. Schweiz Med Wochenschr. 1980;110:1138-1145.
114. Hirt M, Nobel S, Barron E. Zinc nasal
gel for the treatment of common cold symptoms: a double-blind,
placebo-controlled trial. Ear Nose Throat J. 2000;79:778-781.
115. Belongia EA, Berg R, Liu K. A
randomized trial of zinc nasal spray for the treatment of upper
respiratory illness in adults. Am J Med. 2001;111:103-108.
116. Mossad SB, Macknin ML, Medendorp SV,
et al. Zinc gluconate lozenges for treating the common cold: a
randomized, double-blind placebo-controlled study. Ann Intern Med.
1996;125:81-88.
117. Petrus EJ, Lawson KA, Bucci LR.
Randomized, double-masked, placebo-controlled clinical study of the
effectiveness of zinc acetate lozenges on common cold symptoms in
allergy-tested subjects. Curr Ther Res. 1998;59:595-607.
118. Prasad AS, Fitzgerald JT, Bao B, et
al. Duration of symptoms and plasma cytokine levels in patients with the
common cold treated with zinc acetate. A randomized, double-blind,
placebo-controlled trial. Ann Intern Med. 2000;133:245-252.
119. Macknin ML, Piedmonte M, Calendine C,
et al. Zinc gluconate lozenges for treating the common cold in children:
a randomized controlled trial. JAMA. 1998;279:1962-1967.
120. Marshall S. Zinc gluconate and the
common cold. Review of randomized controlled trials. Can Fam
Physician. 1998;44:1037-1042.
121. Eby GA. Linearity in dose-response
from zinc lozenges in treatment of common colds. J Pharm Technol.
1995;11:110-122.
122. Girodon F, Lombard M, Galan P, et al.
Effect of micronutrient supplementation on infection in
institutionalized elderly subjects: a controlled trial. Ann Nutr
Metab. 1997;41:98-107.
123. Sugarman B. Zinc and infection.
Rev Infect Dis. 1983;5:137-147.
124. Sazawal S, Black RE, Jalla S, et al.
Zinc supplementation reduces the incidence of acute lower respiratory
infections in infants and preschool children: a double-blind, controlled
trial. Pediatrics. 1998;102:1-5.
125. Bhutta ZA, Black RE, Brown KH, et al.
Prevention of diarrhea and pneumonia by zinc supplementation in children
in developing countries: Pooled analysis of randomized controlled
trials. J Pediatr. 1999;135:689-697.
126. Godfrey HR, Godfrey NJ, Godfrey JC,
et al. A randomized clinical trial on the treatment of oral herpes with
topical zinc oxide/glycine. Altern Ther Health Med. 2001;7:49-54,
56.
127. Pohit J, Saha KC, Pal B. Zinc status
of acne vulgaris patients. J Appl Nutr. 1985;37:18-25.
128. Amer M, Bahgat MR, Tosson Z, et al.
Serum zinc in acne vulgaris. Int J Dermatol. 1982;21:481-484.
129. Michaelsson G, Vahlquist A, Juhlin L.
Serum zinc and retinol-binding protein in acne. Br J Dermatol.
1977;96:283-286.
130. Goransson K, Liden S, Odsell L. Oral
zinc in acne vulgaris: a clinical and methodological study. Acta Derm
Venereol. 1978;58:443-448.
131. Verma KC, Saini AS, Dhamija SK. Oral
zinc sulfate therapy in acne vulgaris: a double-blind trial. Acta
Derm Venereol. 1980;60:337-340.
132. Weimar VM, Puhl SC, Smith WH, et al.
Zinc sulfate in acne vulgaris. Arch Dermatol. 1978;114:1776-1778.
133. Hillstrom L, Pettersson L, Hellbe L,
et al. Comparison of oral treatment with zinc sulphate and placebo in
acne vulgaris. Br J Dermatol. 1977;97:681-684.
134. Michaelsson G, Juhlin L, Vahlquist A.
Effects of oral zinc and vitamin A in acne. Arch Dermatol.
1977;113:31-36.
135. Dreno B, Amblard P, Agache P, et al.
Low doses of zinc gluconate for inflammatory acne. Acta Derm Venereol.
1989;69:541-543.
136. Weismann K, Wadskov S, Sondergaard J.
Oral zinc sulphate therapy for acne vulgaris. Acta Derm Venereol.
1977;57:357-360.
137. Orris L, Shalita AR, Sibulkin D, et
al. Oral zinc therapy of acne. Absorption and clinical effect. Arch
Dermatol. 1978;114:1018-1020.
138. Michaelsson G, Juhlin L, Ljunghall K.
A double-blind study of the effects of zinc and oxytetracycline in acne
vulgaris. Br J Dermatol. 1977;97:561-566.
139. Cunliffe WJ, Burke B, Dodman B, et
al. A double-blind trial of a zinc sulphate/citrate complex and
tetracycline in the treatment of acne vulgaris. Br J Dermatol.
1979;101:321-325.
140. Gupta VL, Chaubey BS. Efficacy of
zinc therapy in prevention of crisis in sickle-cell anemia: a
double-blind, randomized controlled clinical trial. J Assoc
Physicians India. 1995;43:467-469.
141. Newsome DA, Swartz M, Leone NC, et
al. Oral zinc in macular degeneration. Arch Ophthalmol.
1988;106:192-198.
142. Stur M, Tittl M, Reitner A, et al.
Oral zinc and the second eye in age-related macular degeneration.
Invest Ophthalmol Vis Sci. 1996;37:1225-1235.
143. Mares-Perlman JA, Klein R, Klein BE,
et al. Association of zinc and antioxidant nutrients with age-related
maculopathy. Arch Ophthalmol. 1996;114:991-997.
144. Hoffman HN II, Phyliky RL, Fleming
CR. Zinc-induced copper deficiency. Gastroenterology.
1988;94:508-512.
145. Sandstead HH. Requirements and
toxicity of essential trace elements, illustrated by zinc and copper.
Am J Clin Nutr. 1995;61(suppl 3):621S-624S.
146. Fosmire GJ. Zinc toxicity. Am J
Clin Nutr. 1990;51:225-227.
147. Porea TJ, Belmont JW, Mahoney DH Jr.
Zinc-induced anemia and neutropenia in an adolescent. J Pediatr.
2000;136:688-690.
148. Lim D, McKay M. Food-drug
interactions. Drug Information Bulletin (UCLA Dept. of
Pharmaceutical Services). 1995;15(2).
149. Drug Evaluations Annual. Vol.
2. Milwaukee, Wis: American Medical Association; 1993.
150. Neuvonen PJ. Interactions with the
absorption of tetracyclines. Drugs. 1976;11:45-54.
151. Mapp RK, McCarthy TJ. The effect of
zinc sulphate and of bicitropeptide on tetracycline absorption. S Afr
Med J. 1976;50:1829-1830.
152. Polk RE, Healy DP, Sahai J, et al.
Effect of ferrous sulfate and multivitamins with zinc on absorption of
ciprofloxacin in normal volunteers. Antimicrob Agents Chemother.
1989;33:1841-1844.
153. Campbell NR, Kara M, Hasinoff BB, et
al. Norfloxacin interaction with antacids and minerals. Br J Clin
Pharmacol. 1992;33:115-116.
154. Reyes AJ, Olhaberry JV, Leary WP, et
al. Urinary zinc excretion, diuretics, zinc deficiency and some
side-effects of diuretics. S Afr Med J. 1983;64:936-941.
155. Wester PO. Urinary zinc excretion
during treatment with different diuretics. Acta Med Scand.
1980;208:209-212.
156. Age-Related Eye Disease Study
Research Group. A randomized, placebo-controlled, clinical trial of
high-dose supplementation with vitamins C and E, beta carotene, and zinc
for age-related macular degeneration and vision loss: AREDS Report no.8.
Arch Ophthalmol. 2001;119:1417-1436.
157. Dietary Reference Intakes for Vitamin
A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese,
Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001). Available at
www.nap.edu. Accessed October 4, 2001.
158. Ewing CI, Gibbs AC, Ashcroft C, et
al. Failure of oral zinc supplementation in atopic eczema. Eur J Clin
Nutr. 1991;45:507-510.
159. Simkin PA. Oral zinc sulphate in
rheumatoid arthritis. Lancet. 1976;2:539-542.
160. Peretz A, Neve J, Jeghers O, et al.
Zinc distribution in blood components, inflammatory status, and clinical
indexes of disease activity during zinc supplementation in inflammatory
rheumatic diseases. Am J Clin Nutr. 1993;57:690-694.
161. Zemel BS, Kawchak DA, Fung EB, et.
al. Effect of zinc supplementation on growth and body composition in
children with sickle cell disease. Am J Clin Nutr.
2002;75:300-307.
162. Su JC, Birmingham CL. Zinc
supplementation in the treatment of anorexia nervosa. Eat Weight
Disord. 2002;7:20-22.
Email:
| 