Zinc Abstracts 2


Comparative study of zinc levels in benign and malignant lesions of the prostate.
            (Goel and Sankhwar, 2006)  Download
OBJECTIVES:  The normal human prostate accumulates the highest levels of zinc of any soft tissue in the body. The presence of zinc in the prostate of a number of mammalian species, including rhesus monkeys and humans, has been well documented. The aims of this study were to investigate the concentrations of zinc in various disorders of the prostate and to find a correlation between them. MATERIAL AND METHODS:  A total of 80 cases were studied (20 normal, 50 benign, 10 carcinomatous). A plasma sample was taken and zinc levels were analyzed using atomic absorption spectrophotometry. RESULTS:  The mean (+/-SD) plasma zinc level in the normal cases was 94.5+/-10.38 microg/100 ml. Amongst patients with benign diseases of the prostate gland, the plasma zinc level was 145.4+/-9.67, 162.4+/-2.22 and 172.7+/-5.27 microg/100 ml (78% rise compared to normal patients) in those with a fibromuscular prostate, chronic prostatitis and benign prostatic hyperplasia, respectively, whilst patients with malignancy had a plasma zinc level of 59.6+/-3.08 microg/100 ml (37% fall compared to normal patients). There was a highly statistically significant (p < 0.01) difference in plasma zinc levels between patients with benign and malignant prostate diseases. The effect of metastasis of carcinoma of the prostate on plasma zinc levels was not significant (p > 0.05), while there was a highly statistically significant (p < 0.01) correlation between serum prostate-specific antigen and plasma zinc levels in malignancy. CONCLUSIONS:  There appears to be a strong correlation between plasma zinc levels and various prostatic diseases. Therefore, the determination of zinc levels can be used as a diagnostic or screening tool and may lead to the formulation of methods in which zinc is used to evaluate prostatic pathology.

The efficacy of zinc for treatment of chronic prostatitis.
            (Goodarzi et al., 2013) Download
AIM:  to investigate the efficacy of zinc supplementation in chronic prostatitis treatment. METHODS:  present randomized clinical trial was conducted on 120 patients with diagnosis of chronic prostatitis (IIIA NIH) after preliminary evaluation and ruling out other conditions. The study group received oral zinc sulfate 220 mg daily as capsule without any other supplements. The control group received placebo. Subjects were examined for NIH-CPSI scores every 4 weeks for 12 weeks. RESULTS:  101 subjects completed the study. There were no statistically significant differences in scores and sub-scores of NIH-CPSI between groups before intervention. Decline in the score and sub-scores were more prominent in case group after beginning of the study; though the differences were not statistically significant. Furthermore, the differences in total score and pain score at 12 weeks follow was statistically significant (p=0.003 and p=0.02, respectively). CONCLUSION:  zinc supplements may benefit in management of patients with chronic prostatitis NIH-IIIA. It can be attributable to anti-bacterial and immuno-modulatory functions of organic zinc in the body.

Study of the effects of oral zinc supplementation on peroxynitrite levels, arginase activity and NO synthase activity in seminal plasma of Iraqi asthenospermic patients.
            (Hadwan et al., 2014) Download
BACKGROUND:  Low concentrations of nitric oxide (NO) are necessary for the biology and physiology of spermatozoa, but high levels of NO are toxic and have negative effects on sperm functions. Although several studies have considered the relationship between infertility and semen NO concentrations, no study on the effects of asthenospermia treatments such as oral zinc supplementation on concentrations of NO, which are important in fertility, has been reported. Studies have shown that oral zinc supplementation develops sperm count, motility and the physical characteristics of sperm in animals and in some groups of infertile men. The present study was conducted to study the effect of zinc supplementation on the quantitative and qualitative characteristics of semen, along with enzymes of the NO pathway in the seminal plasma of asthenospermic patients. METHODS:  Semen samples were obtained from 60 fertile and 60 asthenozoospermic infertile men of matched age. The subfertile group was treated with zinc sulfate; each participant took two capsules (220 mg per capsule) per day for 3 months. Semen samples were obtained (before and after zinc sulfate supplementation). After liquefaction of the seminal fluid at room temperature, routine semen analyses were performed. The stable metabolites of NO (nitrite) in seminal plasma were measured by nitrophenol assay. Arginase activity and NO synthase activity were measured spectrophotometrically. RESULTS:  Peroxynitrite levels, arginase activity, NO synthase activity and various sperm parameters were compared among fertile controls and infertile patients (before and after treatment with zinc sulfate). Peroxynitrite levels and NO synthase activity were significantly higher in the infertile patients compared to the fertile group. Conversely, arginase activity was significantly higher in the fertile group than the infertile patients. Peroxynitrite levels, arginase activity and NO synthase activity of the infertile patient were restored to normal values after treatment with zinc sulfate. Volume of semen, progressive sperm motility percentage and total normal sperm count were increased after zinc supplementation. CONCLUSIONS:  Treatment of asthenospermic patients with zinc supplementation leads to restored peroxynitrite levels, arginase activity and NO synthase activity to normal values and gives a statistically significant improvement of semen parameters compared with controls.

Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis.
            (Kim et al., 2014) Download
Zinc deficiency in patients with atopic dermatitis (AD) and the use of zinc supplementation is still controversial. We measured hair zinc levels in 58 children with AD and 43 controls (age range 2-14 years). We also investigated the efficacy of oral zinc supplementation in AD patients with low hair zinc levels by comparing eczema assessment severity index (EASI), transepidermal water loss (TEWL), and visual analogue scales for pruritus and sleep disturbance in patients receiving zinc supplementation (Group A) and others not receiving supplementation (Group B). At baseline, the mean zinc level was significantly reduced in AD patients (113.1 μg/g vs. 130.9 μg/g, p = 0.012). After 8 weeks of supplement, hair zinc level increased significantly in Group A (p < 0.001), and EASI scores, TEWL, and visual analogue scales for pruritus improved more in Group A than in Group B (p = 0.044, 0.015 and < 0.001, respectively). Thus, oral zinc supplementation may be effective in AD patients with low hair zinc levels.

Zinc and zinc transporters in prostate carcinogenesis.
            (Kolenko et al., 2013)  Download
The healthy human prostate accumulates the highest level of zinc of any soft tissue in the body. This unique property is retained in BPH, but is lost in prostatic malignancy, which implicates changes in zinc and its transporters in carcinogenesis. Indeed, zinc concentrations diminish early in the course of prostate carcinogenesis, preceding histopathological changes, and continue to decline during progression toward castration-resistant disease. Numerous studies suggest that increased zinc intake might protect against progression of prostatic malignancy. In spite of increased dietary intake, zinc accumulation might be limited by the diminished expression of zinc uptake transporters, resulting in decreased intratumoural zinc levels. This finding can explain the conflicting results of various epidemiological studies evaluating the role of zinc supplementation on primary and secondary prostate cancer prevention. Overall, more research into the mechanisms of zinc homeostasis are needed to fully understand its impact on prostate carcinogenesis. Only then can the potential of zinc and zinc transport proteins be harnessed in the diagnosis and treatment of men with prostate cancer.

Zinc supplementation inhibits complement activation in age-related macular degeneration.
            (Smailhodzic et al., 2014) Download
UNLABELLED:  Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression. TRIAL REGISTRATION:  The Netherlands National Trial Register NTR2605.

Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation.
            (Wong et al., 2015) Download
SCOPE:  Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age-related immune defects, including chronic inflammation, coincide with declining zinc status. METHODS AND RESULTS:  An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency upregulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, which coincided with increased IL1β and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc-deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals. CONCLUSION:  Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation.

Analysis of serum and urinal copper and zinc in Chinese northeast population with the prediabetes or diabetes with and without complications.
            (Xu et al., 2013) Download
This study investigated the association of copper and zinc levels in the serum or urine of patients living in northeast China, with either prediabetes or diabetes. From January 2010 to October 2011, patients with type 1 diabetes (T1D, n = 25), type 2 diabetes (T2D, n = 137), impaired fasting glucose (IFG, n = 12) or impaired glucose tolerance (IGT, n = 15), and age/gender matched controls (n = 50) were enrolled. In the T2D group, there were 24 patients with nephropathy, 34 with retinopathy, and 50 with peripheral neuropathy. Serum copper levels were significantly higher in IFG, IGT, and T2D groups. Serum zinc level was dramatically lower, and urinary zinc level was significantly higher in both T1D and T2D subjects compared with controls. The serum zinc/copper ratio was significantly lower in all the patients with IFG, ITG, T1D, and T2D. The serum copper level was positively associated with HbA1c in T2D subjects. Simvastatin treatment in T2D patients had no significant effect on serum and urinary copper and zinc. These results suggest the need for further studies of the potential impact of the imbalanced serum copper and zinc levels on metabolic syndrome, diabetes, and diabetic complications.



Goel, T and SN Sankhwar (2006), ‘Comparative study of zinc levels in benign and malignant lesions of the prostate.’, Scand J Urol Nephrol, 40 (2), 108-12. PubMed: 16608807
Goodarzi, D, et al. (2013), ‘The efficacy of zinc for treatment of chronic prostatitis.’, Acta Med Indones, 45 (4), 259-64. PubMed: 24448329
Hadwan, MH, LA Almashhedy, and AR Alsalman (2014), ‘Study of the effects of oral zinc supplementation on peroxynitrite levels, arginase activity and NO synthase activity in seminal plasma of Iraqi asthenospermic patients.’, Reprod Biol Endocrinol, 12 1. PubMed: 24383664
Kim, JE, et al. (2014), ‘Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis.’, Acta Derm Venereol, 94 (5), 558-62. PubMed: 24473704
Kolenko, V, et al. (2013), ‘Zinc and zinc transporters in prostate carcinogenesis.’, Nat Rev Urol, 10 (4), 219-26. PubMed: 23478540
Smailhodzic, D, et al. (2014), ‘Zinc supplementation inhibits complement activation in age-related macular degeneration.’, PLoS One, 9 (11), e112682. PubMed: 25393287
Wong, CP, NA Rinaldi, and E Ho (2015), ‘Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation.’, Mol Nutr Food Res, 59 (5), 991-99. PubMed: 25656040
Xu, J, et al. (2013), ‘Analysis of serum and urinal copper and zinc in Chinese northeast population with the prediabetes or diabetes with and without complications.’, Oxid Med Cell Longev, 2013 635214. PubMed: 24175012