Zinc is found in all organs and tissues of the body, principally intracellularly. Zinc is also present in all body fluids. The highest concentrations of zinc in humans are found in bone, liver, kidney, muscle, and skin.
The adult human body contains approximately two to three grams of zinc. Approximately 0.1% of the total zinc in the body is replaced each day. 1
Zinc is essential for the function of more than 100 enzymes, either as a structural component or for catalytic activity. 2,3 Enzymes requiring zinc have been identified from every enzyme class.
Zinc absorption from foods has been shown to vary from 12 to 59%. When the 1989 RDA was set, a value of 20% was selected as an estimate of absorption to allow for less than optimal zinc absorption or less than optimal food selection. 4 Daily intake of zinc is essential for health because zinc is not stored in the body.
Food processing may reduce bioavailability of zinc. Heating can generate zinc complexes which are resistant to hydrolysis, making the zinc unavailable.
Vitamin C (ascorbic acid) does not interfere with bioavailability of zinc. 5,6
Zinc deficiency is very rare in well-nourished people. However, it is estimated that 25% of people worldwide have zinc deficiency.
Symptoms of zinc deficiency include growth retardation, loss of appetite, weight loss, taste abnormalities, hair loss, diarrhea, delayed sexual maturation, impotence, hypogonadism in males, lesions of the eye and skin, impaired immune function, delayed wound healing, and mental lethargy.
Acute zinc toxicity: Symptoms of acute zinc toxicity include nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, and headaches.
Chronic zinc toxicity: Chronic effects of zinc toxicity include low copper status, altered iron function, reduced immune function, and reduced levels of high-density lipoproteins. Poor copper status, as measured by copper loading of a specific copper enzyme, was reported with moderately high zinc intakes (60 mg/day for up to 10 weeks).3 Also, the dose of zinc used in the AREDS study (80 mg per day of zinc in the form of zinc oxide for 6.3 years, on average) was associated with a significant increase in hospitalizations for genitourinary causes. It has been suggested that chronic intake of high levels of zinc alters some aspects of urinary physiology.12
Good dietary sources of zinc include: oysters, red meat, poultry, fish, eggs, crabmeat, shellfish, liver, fortified cereals, dairy, peanuts, lima beans, blackeyed peas, cooked oats, whole grains, and wheat germ. Phytates are present in whole-grain breads, cereals, legumes, and other plant foods. These compounds are the principal storage of phosphorus in plant tissues. Phytates bind zinc and prevent uptake in nonruminant animals (such as humans). Zinc is more available from leavened grain products (such as breads) than from unleavened products (such as flatbreads or crackers); the leavening process partially breaks down phytates.
Although zinc deficiency is rare in well-nourished populations, certain conditions and diseases can increase zinc requirements, increase zinc losses, or reduce zinc absorption. Careful food choices and zinc supplements can help to alleviate insufficiencies.
Gastrointestinal surgery and digestive disorders (such as ulcerative colitis, Crohn's disease, and short bowel syndrome), impair zinc absorption or increase zinc losses, increasing risk for zinc deficiency.
People with diabetes frequently also have zincuria. Zinc supplements or diets high in zinc may help to replace zinc lost in urine. 1
Vegetarians are at risk for zinc deficiency or inadequacy because absorption of zinc from a vegetarian diet is impared by phytates.
Pregnant and lactating women have higher requirements for zinc. Older infants who are exclusively breastfed are also at risk for zinc insufficiency.
Zinc absorption is reduced and zinc excretion is increased by alcohol; alcoholics are at risk for zinc deficiency. Approximately 30-50% of alcoholics have zinc deficiency.
People with sickle cell disease are at risk for zinc deficiency.
Quinolone antibiotics13 and tetracycline antibiotics14 bind zinc in the gastrointestinal tract. The absorption of both zinc and the antibiotic is impaired. Zinc supplements should be taken at least two hours prior to or four hours after these antibiotics to reduce this reaction.
Penicillamine is used to treat rheumatoid arthritis. Zinc reduces the absorption and action of penicillamine. Zinc and penicillamine should be taken at least two hours apart.
Thiazide diuretics increase urinary excretion of zinc and can lead to deficiency.15 People who are taking these drugs for long periods of time should be monitored for zinc status.
Thirteen trials investigating the treatment of cold symptoms were included, totaling 966 participants. Two preventive trials were included with 394 participants. Taken within twenty-four hours of the onset of common cold symptoms, consumption of zinc supplements was associated with a significant reduction in the duration and severity of symptoms (respectively, standardized mean difference (SMD) -0.97, 95% confidence interval (CI) -1.56 to -0.38, P = 0.001; SMD -0.39, 95% CI -0.77 to -0.02, P = 0.04). Fewer participants consuming zinc supplements continued to have symptoms after seven days than those in the placebo group (OR 0.45, 95% CI 0.2 to 1.00, P = 0.05). In the trials evaluating the prevention of common cold with zinc supplements, the incidence rate ratio (IRR) was reduced with zinc supplementation (IRR 0.64, 95% CI 0.47 to 0.88, P = 0.006). School absences were reduced in the zinc group compared to the placebo group (P = 0.0003). Prescription of antibiotics (P < 0.00001) was lower in the zinc group compared to the placebo group. Adverse events including bad taste and nausea were higher in the zzinc group. The authors of the review concluded that current evidence supports the idea that zinc supplements reduce both the severity and incidence of common cold but that a specific recommendation for dosage or duration cannot be made due to variations in current studies.16
Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor in patients with common cold treated with zinc acetate.
A randomized, double-blind, placebo-controlled trial investigated the use of zinc acetate for common cold symptoms. Fifty volunteers suffering from common cold symptoms for less than twenty-four hours were recruited to participate in the study. Participants consumed zinc acetate-containing lozenges (13.3 mg zinc per lozenge) or a placebo every two to three hours while awake. The doses of zinc were approximately 70 to 100 mg daily. For assessment of efficacy, participants recorded subjective scores for common cold symptoms daily; additionally, plasma zinc, soluble interleukin (IL)-1 receptor antagonist, soluble tumor necrosis factor receptor 1, soluble vascular endothelial cell adhesion molecule, and soluble intercellular adhesion molecule-1 were assayed on days 1 and 5. Compared to the placebo group, common cold symptoms were significantly reduced in the zinc group. In the zinc group, mean overall duration of cold was shortened relative to placebo (4.0 vs. 7.1 days; P < 0.0001). Relative to placebo, the zinc group had shorter durations of cough (2.1 vs. 5.0 days; P < 0.0001) and nasal discharge (3.0 vs. 4.5 days, P = 0.02). These results suggest that zinc in the form of zinc acetate is effective for common cold symptoms and duration. Further studies to evaluate the necessary amount of zinc will help to clarify the results.17
Zinc lozenges as cure for the common cold--a review and hypothesis.
The results of clinical trials suggest that this ionic zinc is also responsible for activity in people suffering from the common cold. Solution chemistry evaluations of various forms of zinc used in lozenges demonstrates that zinc acetate releases nearly 100% of ionic zinc and zinc gluconate releases 72% of ionic zinc. Other zinc forms release significantly less to no ionic zinc. In clinical trials, ionic zinc from lozenges was found to reduce common cold duration (mean duration P<0.001; and median duration P<0.004). Total zinc was not correlated with changes in common cold duration. Sometimes additional ligands are added to mask the flavor of zinc in lozenges; however, these additive ligands damaged or eliminated efficacy. Reduction of cold duration for multi-ligand zinc gluconate and zinc acetate lozenges (mean 0 days, median 0.43 days) was significantly less than the reduction of duration for single ligand zinc gluconate or acetate lozenges (mean 3.37 days, median 2.9 days) (P<0.001). Zinc compounds with low stability released higher levels of ionic zinc and five of six trials with such compounds succeeded; only two of nine trials with lozenges composed of zinc compounds with high stability were successful at reducing duration of the common cold (P<0.02). This review suggests that the composition of lozenges for common cold reduction is very important. Lozenges with single ligand zinc gluconate or zinc acetate have been found to be the most effective.18
Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress.
A randomized, double-blind, placebo-controlled trial investigated the effects of zinc supplements on immune function in a group of older participants. Fifty men and women aged 55 to 87 years participated in the one year trial. Participants were randomly assigned to receive 45 mg zinc daily (as zinc gluconate) or a placebo daily for twelve months. At baseline, approximately 35% of participants were zinc deficient. Zinc supplements significantly reduced the incidence of infections among participants compared to placebo (29% vs. 88%; P<0.0001). In the zinc group, mean incidence of infections per subject in 12 months was lower (0.29 ± 0.46; P < 0.01) than in the placebo group (1.4 ± 0.95; effect size: 1.46). The results of this study suggest that zinc supplements improved immune function for this group of older participants. Further studies are needed to clarify the mechanisms involved.19
A randomized, prospective, placebo-controlled clinical trial of a novel zinc-monocysteine compound in are-related macular degeneration.
A randomized, prospective, placebo-controlled clinical trial investigated the use of zinc-monocysteine for people with dry age-related macular degeneration (AMD). Eighty people participated in the six month trial. Participants were diagnosed with dry AMD and had best-corrected visual acuity 20/25 to 20/70, macular drusen, and pigment changes. Participants were randomly assigned to receive 25 mg zinc-monocysteine twice daily or a placebo. Best-corrected visual acuity, contrast sensitivity, and light-flash recovery time were assessed at baseline, three months, and six months for all participants. The zinc monocysteine group showed improved visual acuity (p < 0.0001) and contrast sensitivity (p < 0.0001) after six months. After three months, the zinc monocysteine group showed shortened macular light flash recovery time compared to baseline (left eye, 2.1 s, p = 0.0001; right eye, 3.6 s, p < 0.0001); after six months light flash recovery time was further shortened in the zinc monocysteine group compared to baseline (left eye, 7.2 s, p < 0.0001; right eye, 7.4 s, p < 0.0001). These results suggest that zinc monocysteine may improve symptoms of AMD. It should be noted that zinc monocysteine is currently not a commercially available supplemental form of zinc; it is currently being evaluated as a pharmaceutical compound.20
Antioxidant supplements to prevent or slow down the progression of AMD: a systematic review and meta-analysis.
A meta-analysis of clinical trials of antioxidant supplements for age-related macular degeneration (AMD) evaluated the utility of these supplements. Three trials were included; a total of 23,099 participants were part of these trials. Trials had a duration ranging from four to twelve years. The pooled risk ratio for AMD was 1.03 (95% CI, 0.74-1.43). Antioxidant (beta-carotene, vitamin C, and vitamin E) and zinc supplementation were found to slow progression to advanced AMD (adjusted odds ratio=0.68, 95% CI, 0.53-0.87) and visual acuity loss (0.77, 95% CI, 0.62-0.96, respectively). The results of this meta-analysis suggest that antioxidants or zinc may slow progression of AMD. Further studies are necessary to evaluate the efficacy of zinc and antioxidants for AMD.21
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