Zinc

James Meschino DC, MS, ROHP

General Features
Zinc is ubiquitous in plants, micro organisms and animals.  The average adult body contains 1.5 to 3.0 mg of zinc with approximately 60 percent in muscles, 30 percent in bones and 6 percent in skin.  The highest concentrations of zinc are in the prostate gland and sperm in men, and in red and white blood cells.  The retina of the eye, liver and kidneys also have high concentrations.

Zinc functions in over 200 (possibly 300) enzymatic reactions in the body.  It is found in every body cell, and is involved in numerous functions including synthesis and stabilization of genetic material, cell division, immune function, synthesis and secretion of insulin and other hormones, wound healing, maintenance of healthy skin, neurotransmitter function, vision, taste acuity, sense of smell, hydrochloric acid production in the stomach, prostaglandin synthesis, muscle contraction, alcohol detoxification, prostate function, testicular development, sperm production and other functions.  In fact, zinc functions in more enzymatic reactions than any other material.

Zinc Deficiency
Overt zinc deficiency can result in eczema (face and hands), hair loss, mental apathy, low sperm count, testicular atrophy, delayed sexual maturation, menstrual irregularities, decreased growth and impaired mental development.  Loss of taste acuity, sense of smell, anemia, delayed wound healing, susceptibility to infections, impotence in men and nerve damage are other possible signs and symptoms of sub-optimal zinc status.

Acrodermatitis enteropathica, a rare disease in infancy, is caused by a genetic inability to absorb zinc.  Skin rashes appear when a baby is young.  When breastfeeding is stopped, gastrointestinal problems, decreased growth and mental abnormalities are seen.

Absorption and Metabolism
The exact site of zinc absorption has not been determined, but data suggest the ileum as the primary site.  On average, 20 to 40 percent of dietary zinc is absorbed.  Zinc absorption decreases with age.  People over 65 may absorb only half as much zinc as those 25 to 30 years of age.

Zinc is absorbed via an energy-dependent carrier system that involves citric acid, picolinic acid, vitamin B₆ and possibly other yet undetermined compounds.  High intakes of copper can inhibit zinc absorption, but this is not a concern in regards to most multiple vitamin and mineral products, where there is typically more zinc than copper.  An intake of iron to zinc that exceeds 3:1 can also impair zinc absorption.  Most well-designed vitamin and mineral products do not exceed a 3:1 ratio of iron to zinc and are, therefore, a bioavailable source of both minerals.

Albumin is the main transport protein for zinc in the blood, but some is also bound to transferrin, ceruloplasmin, and gamma globulin.  Zinc excretion is almost solely via feces in healthy individuals.  Increased urinary zinc loss signifies nephrosis, diabetes, alcoholism, hepatic cirrhosis, porphyria, or starvation.¹

Recommended Daily Allowance (Zinc)

Supplementation Studies and Clinical Applications

1. Benign Prostatic Hyperplasia (BPH)

Zinc supplementation has been shown to reverse symptoms of BPH.^3,4  Zinc has been shown to inhibit the activity of the 5-alpha-reductase enzyme that irreversibly converts testosterone to dihydrotestosterone (DHT).  DHT is linked to accelerated prostate cell division, proliferation and BPH.  Zinc also inhibits specific binding of androgens to the cystosol and nuclear androgen receptors.^5,6  Zinc has also been shown to inhibit prolactin secretion by the pituitary, an effect that also reverses and helps to prevent BPH.  Prolactin increases the uptake of testostorone by the prostate, thereby increasing the potential build up of DHT.^7,8,9  Short-term studies have used as much as 45-60 mg of zinc per day.

2. Wound Healing

Delayed wound healing as people age may be related, in part, to sub-optimal zinc status.  Zinc supplementation has been shown to accelerate healing of various wounds, including post-surgical applications, gastric ulcers and venous leg ulcerations.^10-13  Zinc supplementation up to 150 mg per day has been used in these trials.  However, at this level, zinc may impair immune function and produce other side effects, such as depressed HDL levels and anemia.¹⁴

Other authorities suggest that 30-50 mg per day is adequate to boost wound healing potential in these patients.¹⁵

3. Male Infertility

A number of studies have shown that zinc supplementation can raise sperm counts (8-20 million per millilitre) in men with low sperm counts and low blood levels of testosterone.  Zinc supplementation also raised testosterone levels in these subjects.  In men with normal testosterone levels, zinc supplementation is less likely to increase sperm count.^16,17,18  Daily supplementation of 60 mg zinc per day has been used for this application.

4. Macular Degeneration

In a study conducted at the Department of Ophthalmology at the Utah School of Medicine, 151 patients with macular degeneration received either 100 mg of zinc or placebo.  Those receiving zinc had significantly less loss of vision.¹⁹  The study period was 12-24 months.  These results were not confirmed in a more recent double-blind study of 112 patients.²⁰

5. Immune Function

Poor zinc status is linked to low T-cell counts, thymic hormone levels and reduced immune function in general.

Zinc supplementation produces a reversal of the low immune function characteristics associated with aging.  Marginal zinc deficiencies are common in aging and very prevalent in the elderly.^19,20

Studies on institutionalized elderly reveal that 20 mg of zinc supplementation per day raised serum thymulin (a thymus gland hormone that declines with age) and immune function.²¹

6. Other Potential Applications
   a.Acne (several double-blind studies)

6. 6. b.Rheumatoid Arthritis – mild effect

6. 6. c. Alzheimer’s Disease – single study yielded good results

6. 6. d. Wilson’s Disease – zinc blocks copper absorption, helping to prevent copper accumulation (Requires medical supervision as high doses are required).2

6. 6. e. Osteoporosis Prevention – via increased synthesis of insulin-like growth factor-1 and the effects on enhanced protein synthesis and bone density related to these effects.22

6. f. Common cold – zinc lozenges shorten duration of colds in some, but not all studies (direct anti-viral action).6 Best results with zinc gluconate or zinc gluconate-glycine lozenges containing 15-25 mg of zinc per lozenge.23,24

Dosage Ranges

1. General Health Support: 15-20 mg (Adults) – average intake from food alone is only 8-9 mg per day.
2. Benign Prostatic Hyperplasia: 30-50 mg
3. Wound Healing: 30-50 mg
4. Low Sperm Count and Low Testosterone: 60 mg
5. Macular Degeneration: 100 mg (one year) (50-80 mg also shown to be effective)
6. Immune Strengthening: 20-50 mg¹⁵
7. Osteoporosis prevention (postmenopausal): 15-20 mg²²
8. Common cold: zinc lozenges (15-25 mg), 4-5 per day for several days only^23,24

Side Effects and Toxicity

Zinc is a very safe nutrient if taken at commonly cited intake levels (15-30 mg per day).  At higher levels, such as 150 mg per day, it can reduce HDL-cholesterol levels, induce copper–deficiency anemia and impair immune function. Acute toxicity causes vomiting.  If taken on an empty stomach, zinc supplements can produce gastrointestional upset and nausea.^2,14

Some authorities caution against the long-term supplementation of more than 50 mg of zinc per day.¹⁵

Drug-Nutrient Interactions
A great number of drugs either impair zinc absorption or deplete zinc status.  The most common drugs that may increase zinc requirements include:

1. Anticonvulsants (e.g. sodium valproate)
2. Caffeine
3. Alcohol
4. Hormone Replacement therapy²⁵

The following drugs have been shown to deplete zinc status:

1. H-2 Receptor Antagonists (antacids): reducing acidity, reduces zinc absorption²⁶
2. Tetracyclines: these drugs bind to zinc in the intestinal tract reducing absorption of the drug and the mineral^27,28
3. ACE Inhibitors: increase urinary loss of zinc²⁹
4. Clofibrate³⁰
5. Corticosteroid drugs: increase zinc excretion^31,32
6. Ethambutol (animal study)³³
7. Loop Diuretics: increase urinary excretion of zinc³⁴
8. Oral Contraceptives³⁵
9. Penicillamine³⁶
10. Thiazide Diuretics: increase urinary excretion of zinc³⁷
11. Valproic Acid³⁸
12. Zidovudine (AZT)³⁹

Nutrient-Nutrient Interactions

1. Copper: high intake of copper or zinc can reduce the absorption of the other.^40,41
2. Iron: high intake of copper or iron can reduce the absorption of the other.^42,43

1. Standard Textbooks of Nutritional Science:

– Shils M, Shike M, Olson J, Ross C.  Modern Nutrition in Health and Disease. 9^th ed.  Baltimore, MD: Lippincott Williams & Wilkins; 1993.

– Escott-Stump S, Mahan LK, editors.  Food, Nutrition and Diet Therapy. 10^th ed.  Philadelphia, PA: W.B. Saunders Company; 2000.

– Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8^th ed.  Washington, DC:.ILSI Press; 2001.

– Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective. 2^nd ed.  Upper Saddle River, NJ: Prentice Hall Inc.; 1987.

2. Murray M. Encyclopedia of nutritional supplements. Rocklin, CA: Prima Publishing; 1996.  181-9.
3. Fahim MS, Fahim Z, Der R, Harman J. Zinc treatment for the reduction of hyperplasia of the prostate.  Fed Proc 1976;35:361.
4. Leake A, Chrisholm GD, Busuttil A, Habib FK. Subcellular distribution of zinc in the benign and malignant human prostate: evidence for a direct zinc androgen interaction.  Acta endocrinol 1984;105:281-8.
5. 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;20:651-5.
6. Wallae AM, Grant JK. Effect of zinc on androgen metabolism in the human hyperplastic prostate.  Biochem Soc Trans 1975;3:540-2.
7. Judd AM, MacLeod RM, Login IS. Zinc acutely selectively and reversibly inhibits pituitary prolactin secretion.  Brain Res 1984;294:190-2.
8. Login IS, Thorner MO, MacLeod RM. Zinc may have a physiological role in regulating pituitary prolactin secretion.  Neuroendocrinology 1983;37:317-20.
9. Farnsworth WF, et al. Interaction of prolactin and testosterone in the human prostate.  Urol Res 1981;9:79-88.
10. Pories WJ, Henzel JH, Rob CG, Strain WH. Acceleration of wound healing in man with zinc sulphate given by mouth.  Lancet 1969;1:1069.
11. Greaves MW, Ive FA. Double-blind trial of zinc sulphate in the treatment of chronic venous leg ulceration.  Br J Derm 1972;87:632.
12. Frommes DJ. The healing of gastric ulcers by zinc sulphate.  Med J Aust 1975;2:793.
13. Young B, Ott L, Kasarskis E, Rapp R, Moles K, Dempsey R, et al. Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury.  J Neurotrauma 1996;1:25-34.
14. Hendler S. The doctors’ vitamin and mineral encyclopedia.  New York, NY: Simon and Schuster; 1990.  205-6.
15. Lieberman S, Bruning N. The real vitamin and mineral book.  Garden City Park, NY: Avery Publishing Group; 1997.  148-54.
16. Tikkiwal M, Ajmera RL, Mathur NK. Effect of zinc administration on seminal zinc and fertility of oligospermic males.  Ind J Phys Pharmacol 1987;31:30-4.
17. Takihara H, Cosentino MJ, Cockett AT. Zinc sulfate therapy for infertile males with or without varicocelectomy. Urology 1987;29:638-41.
18. Netter A, Hartoma R, Nahoul K. Effect of zinc administration on plasma testosterone, dihydrotestosterone and sperm count.  Arch Androl 1981;7:69-73.
19. Newsome DA, Swartz M, Leone NC, Elston NC, Miller E. Oral zinc in macular degeneration.  Arch ophthalmol 1988;106:192-8.
20. Stur M, Tihl M, Reitner A, Meisinger V. Oral zinc and the second eye in age-related macular degeneration.  Invest ophthalmol Vis Sci 1996;37:1225-35.
21. Boukaiba N, Flament C, Acher S, Chappuis P, Piau A, Fusselier M, et al. A physiological amount of zinc supplementation: effects on nutritional, lipid and thymic status in an elderly population.  Am J Clin Nutr 1993;57:566-72.
22. Devine A, Rosen C, Mohan S, Baylink D, Prince R. Effects of zinc and other nutritional factors on insulin-like growth factor-1 and insulin-like growth factor binding proteins in postmenopausal women.  Am J Clin Nutr 1998;68(1):200-6.
23. Mossad SB, Macknin ML, Medendorp SV, Mason P. Zinc gluconate lozenges for treating the common cold.  Ann Int Med 1996;125:81-8.
24. Garland ML, Hagmeyer KO. The role of zinc lozenges in treatment of the common cold.  Ann Pharmacother 1998;32:93-6.
25. Reavley N. The new encyclopedia of vitamins, minerals, supplements, and herbs.  New York, NY: M. Evans and Company Inc.; 1998.  324.
26. Sturniolo GC, Montino MC, Rossetto L, Martin A, D’Inca R, D’Odorico A, et al. Inhibition of gastric acid secretion reduces zinc absorption in man.  J Am Coll Nutr 1991;10(4):372-5.
27. Mapp RK, McCarthy TJ. The effect of zinc sulphate and of bicitropeptide on tetracycline absorption.  S Afr Med J 1976;50(45):1829-30.
28. Penttila O, Hurme H, Neuvonen PJ. Effect of zinc sulphate on the absorption of tetracycline and doxycycline in man.  Eur J Clin Pharmacol 1975;9(2-3):131-4.
29. Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, et al. Effects of captopril and enalapril on zinc metabolism in hypertensive patients.  J Am Coll Nutr 1998;17(1):75-8.
30. Powanda MC. Clofibrate-induced alterations in zinc, iron and copper metabolism.  Biochem Pharmacol 1978;27(1):125-27.
31. Fontaine J, Neve J, Peretz A, et al. Effects of acute and chronic prednisolone treatment on serum zinc levels in rats with adjuvant arthritis.  Agents Actions 1991;33(3-4):247-53.
32. Fell GS, et al. Urinary zinc levels as an indicator of muscle catabolism. Lancet 1973Feb;1(7798):280-2
33. Solecki TJ, Aviv A, Bogden JD. Effect of a chelating drug on balance and tissue distribution of four essential metals.  Toxicology 1984;31:207-16.
34. Wester PO. Urinary zinc excretion during treatment with different diuretics.  Acta Med Scand 1980;208(3):209-12.
35. Dorea JG, Ferraz E, Queiroz EF. Effects of anovulatory steroids on serum levels of zinc and copper.  Arch Latinoam Nutr 1982;32(1):101-10.
36. Lu JX, Combs GF Jr. Penicillamine: pharmacokinetics and differential effects on zinc and copper status in chicks.  J Nutr 1992;122(2):355-62.
37. Mountokalakis T, Dourakis S, Karatzas N, Maravelias C, Koutselinis A. Zinc deficiency in mild hypertensive patients treated with diuretics.  J Hypertens Suppl 1984;2(3):S571-2.
38. Hurd RW, Van Rinsvelt HA, Wilder BJ, Karas B, Maenhaut W, De Reu L. Selenium, zinc, and copper changes with valproic acid: possible relation to drug side effects.  Neurology 1984;34(10):1393-5.
39. Baum MK, Javier JJ, Mantero-Atienza E, Beach RS, Fletcher MA, Sauberlich HE, et al. Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males.  J Acquir Immune Defic Syndr 1991;4(12):1218-26.
40. Cossack ZT, van den Hamer CJ. Kinetics of copper absorption in zinc-overload states and following the withdrawal of zinc supplement:  the role of endogenous zinc status.  J Pediatr Gastroenterol Nutr 1987;6(2):296-301.
41. Hoogenradd TU, Van den Hamer CJ. 3 years of continuous oral zinc therapy in 4 patients with Wilson’s Disease.  Acta Neurol Scand 1983;67(6):356-64.
42. 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 Nut 1981;34(4):475-82.
43. Rossander-Hulten L, Brune M, Sandstrom B, Lonnerdal B, Hallberg L. Competitive inhibition of iron absorption by manganese and zinc in humans.  Am J Clin Nutr 1991;54(1):152-6.