MEJAA

SERUM ZINC AND COPPER CONCENTRATION
IN HUMAN AGE-RELATED CATARACT

Issa Nourmohammadi, PhD1
College of Allied Medicine, Cellular Molecular Research Center
Iran University of Medical Sciences,
Tehran, Iran

Mansour Mirsamadi
Department of Ophthalmology
Iran University of Medical Science
Tehran, Iran

Keywords: Zinc, copper, trace elements, cataract

Abstract

Background: There is much evidence suggesting that nutrition and nutritional factors, especially the trace elements zinc and copper may play a role in the formation of human cataract, a disease that is on the increase due to the growing percentage of elderly persons in the world population.
Objective: We have evaluated the serum levels of zinc and copper in cataractic subjects and compared these findings to the levels of healthy controls to supplement our earlier research on the status of other biochemical factors in cataract patients.
Methods: A group of patients diagnosed with cataract and a group of healthy controls were chosen as subjects. Serum was analyzed by flame atomic absorption spectrophotometry for zinc and copper content. Results were statistically evaluated by SPSS/PC software and student t-test.
Findings: A significant difference was found in mean zinc and copper concentrations in comparison of patient group to control group (p < 0.05). Both serum zinc and copper levels in patient group were found to be lower than that of control group.
Conclusion: In spite of the fact that this study was carried out on a relatively small sample population, the findings suggest some thought-provoking questions, considering that there has been a good amount of controversy regarding the status of these trace elements and their possible role in senile cataractogenesis suggesting the need for further studies.

Introduction

As we enter the early years of the third millennium and we witness a steady rise in the mean age of the global population, we are faced with greater challenges in meeting the needs of this growing segment of society as their health and nutritional problems become more critical. A rise in the prevalence of senile cataract is one of the consequences of this expanding

elderly population.^1,2 The causes of cataract, the world's largest single cause of blindness, are multifactorial and the disorder is a major financial burden on both the individual and health care systems.^4,5 Animal and human studies have for years suggested an association between nutrition and ocular lens opacitication (cataract) and, subsequently various inorganic minerals have been linked to cataract formation.^4,5 Among these elements, zinc (Zn) and copper (Cu) have recently attracted much attention as possible causative factors in development of cataract.^6,7,8 Animal studies and in vitro experiments found unspecified diet-related cataract in certain animals in published reports from a number of countries. Diets low in total protein and high in lactose and phytic acid have been identified as determinants of cataract formation in animals.^9,10,11 Ketola¹² fed a diet containing 40% white fish meal of high ash content to rainbow trout (Salmo garidneri) fry and observed lenticular opacities in 87%. Increasing the dietary calcium, phosphorus, sodium and potassium content increased the cataract incidence to 98%. By contrast, supplementation of diet with Zn successfully prevented the appearance of cataract. Zn is a constituent of various metalloenzymes and is found in abundance in the eye, hence, there has been much speculation on the correlation between Zn deficiency and visual impairment and investigators have begun to question the role that Zn could play in eye related disease.¹³ In addition, it has been hypothesized that transitional metal ion-catalyzed formation of hydroxyl radical (HOo) could contribute to the protein modification observed in cataract and may play a role in the etiology of age-related cataract.¹⁴ Studies on Cu and Zn found concentrations of this element to be higher in cataract lens compared to healthy controls.^7,8 The Iranian population is unique in terms of its dietary regimes and nutritional habits and there is scarce information relating to the correlation of Zn and Cu status and cataract in Iranian subjects. This investigation was undertaken to determine the serum levels of Zn and Cu of patients with cataract and to supplement our previous results on our continuing and extensive investigation into status of trace elements in cataract patients. ^15,16.17

Patients and Methods

We recruited 69 patients diagnosed as having cataract, 37 males and 32 females and 51 eligible controls, 21 male and 30 female. Both groups were interviewed and asked to complete a questionnaire concerning their use of drugs, including use of any diabetes medication or steroids, smoking or other habits that could affect the outcome of the results. Patients and controls were categorized in terms of occupation such as agricultural worker, housewife, laborer or other. An ophthalmologist gave all patients and controls a routine eye examination including visual activity, slit lamp examination, ophthalmoscopy, intraocular pressure and blood pressure control (high blood pressure considered having a systolic pressure of 140-190 mmHg for more than 10 years). 40% of our patients reported a positive family history for cataract. 74.8% had cataract of one eye only; and 25.2% had cataract in both eyes. Blood samples were collected in metal-free tubes from patients and controls after an overnight fast. Serum was removed by centrifugation, weighed and stored in pre-cleaned metal-free tubes at -86° C until analysis. Zn and Cu levels in both patients and controls were determined by flame atomic absorption spectrophotometry (UNICAM 929, UK). Samples were diluted by dionized water by a factor of 4. Calibration was done by the standard addition method. All determinations were made in triplicate and results were averaged. The instrumental parameters adopted are reported in Table 1. The data are expressed as mean ± SD by using SPSS/PC software. Comparisons between patient and control groups were made using student T-test.

Results

Total serum Zn level for male and female patients combined was determined to be 123.39 ± 76.94 µg/dl and that figure for controls was 146.84 ± 41.33 µg/dl. Statistical analysis showed these results to be statistically significant with p < 0.05. Total mean Cu level in patients was 119.51 ± 48.70 µg/dl and that for controls, 147.57 ± 63.0 µg/dl, indicating a significant difference between the two study groups (p < 0.05).
In comparing female patients to female controls, we found no significant difference in either Zn levels or Cu levels even though both Zn and Cu levels in female patients were lower than that of controls, (p > 0.05).
In our evaluation of male patients to male controls, we found the mean levels of Zn to have no meaningful difference with p > 0.05. Cu value for male patients was 110.39 ± 20.71 µg/dl and for controls, 135.54 ± 68.07 µg/dl. Analysis of these results indicated a significant difference (p < 0.05).
Statistical evaluation of data revealed no significant difference in Zn levels of male patients when compared to female patients. However, a meaningful difference was found in Cu levels of male patients compared to female patients (p < 0.05).

Conclusion

Although these results are from a relatively small sample population and limited only to serum content of Zn and Cu, they indicate some thought-provoking findings. This is particularly true when we consider that there has been a good amount of controversy regarding the status of these trace elements in serum as well as in the tissue of the eye like aqueous humor and lens and their possible role in senile cataractogenesis. Akyol⁶ on a study of cataract patients reported serum Zn concentration within the normal range (80-140 µg/dl), whereas Cu concentrations were slightly higher (90-160 µg/dl) and no significant difference was found. Jacques¹⁸ studied serum Cu levels and increased risk of cataract but the association was not statistically significant.
Bhat¹⁹ in a study in India showed that plasma levels of Zn and Cu were lower in patients compared to controls but Mohan²⁰ and his colleagues in a larger study were unable to demonstrate such association.
Here we observed significant differences in Zn and Cu serum levels comparing controls and cataract patients. In addition, in contrast with Akyol,⁶ comparing levels of Cu and Zn, we showed a higher level of Zn and lower level of Cu supporting the negative correlation existing between the two indicating that Zn and Cu have an antagonistic effect on one another.
Poor Zn intake might result in deficiency and loss of Zn-dependent coenzymes associated with age related cataract and pharmacological Zn might well provide some protection against vision loss.¹³ Several epidemiological studies suggest a possible role for Zn, and also Cu, as an antioxidant in reducing cataract because both are cofactors for superoxide dismutase (SOD) which is believed to protect the lens protein from oxidation.²¹ In our previous study¹⁵ we found SOD activity increased in cataract patients while Girodon²² did not report a correlation between Zn and Cu serum levels and SOD activity. Some claim the body's defense mechanism activates the increase in synthesis of SOD thereby combating the effects of the oxidation process.^18,20
Levels of Zn and Cu increase in cataractic lenses^7,8,23 but our lower serum levels maybe due to the accumulation of these elements in the lens reflecting the build-up of metal-associated molecules that may accumulate with age or increase in highly polluted areas. The build-up of metal-associated molecules such as proteins causes oxidation of the sulfahydrate group causing protein damage and eventually leading to cataract.⁸
In animal studies, metabolic alteration responsible for Zn deficient cataracts has been ascribed to dietary calcium interfering with Zn utilization due to the fact that high calcium (and phosphorus) will reduce Zn bioavailibility.¹² Low Zn levels due to high dietary phytate and other mineral binding agents in food which act as chelating agents may be important in initiating cataract formation.¹¹ It has also been reported that during stress caused by infection or inflammation, there is a metabolic alteration in the levels of Zn and Cu.²⁴
Since there is much evidence suggesting that nutrition may influence cataract occurrence in humans, results on the nutritional factors studied in this investigation are consistent with the hypothesis that cataract formation may be due to the status of trace elements such as Zn and Cu. Several epidemiological studies from various countries on elderly subjects showed lower Zn levels with values ranging from 18% lower levels to 40%.²² However, whether these concentration changes are the actual cause of cataract development or are the consequence of disease itself must be further studied. We should also carry out more assessment on the safety and efficacy of Zn and Cu dietary supplementation in the treatment of senile cataract.

Acknowledgements:

This research was conducted at the Cellular and Molecular Biology Research Center (IUMS). Our thanks to Drs. Moddares, Pakdel and Mohebi for their long discussions with one of the authors and their invaluable advice. We would also like to thank Ehsan Noor-Mohammadi for editing of the manuscript.