Studying the association between cigarette smoking and serum copper, zinc, and magnesium concentrations: A cross-sectional study

Asmaa Mahmoud Mohammed; Adel F Hashish; Gamila S El-Saeed

doi:10.4103/jphpc.jphpc_36_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 4 | Issue : 1 | Page : 42-47

Studying the association between cigarette smoking and serum copper, zinc, and magnesium concentrations: A cross-sectional study

Asmaa Mahmoud Mohammed¹, Adel F Hashish², Gamila S El-Saeed³
¹ Department of Environmental and Occupational Medicine, National Research Centre, Doki, Egypt
² Department of Researches of Children with Special Needs, National Research Centre, Doki, Egypt
³ Department of Medical Biochimestry, National Research Centre, Doki, Egypt

Date of Submission	27-Aug-2022
Date of Decision	16-Sep-2022
Date of Acceptance	10-Oct-2022
Date of Web Publication	15-Feb-2023

Correspondence Address:
Dr. Asmaa Mahmoud Mohammed
Department of Environmental and Occupational Medicine, National Research Centre,12622, Doki
Egypt

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jphpc.jphpc_36_22

Abstract

Background and Objectives: Tobacco smoking causes damages almost for every organ in the body. Based on the literature review, the relationship between smoking, including nicotine dependence, and the serum zinc (Zn), copper (Cu), magnesium (Mg) status has not been studied sufficiently. The aim of the present study was to determine the relationship of cigarette smoking, including the nicotine dependence state of the smokers, with serum Cu, Zn, and Mg concentrations. Subjects and Methods: Overall, 41 active smokers and 44 nonsmokers were investigated for serum Cu, Zn, and Mg concentrations; in addition to urinary cotinine/creatinine ratio. The eight-item Fagerstrom test for nicotine dependence (FTND) questionnaire has been used to determine the nicotine dependence status of the smokers. Results: A significant hypozincemia has been detected in 34.1% of the smokers versus 9.1% of nonsmokers, with a five-fold higher risk than nonsmokers. Moreover, a significant hypomagnesemia has been detected in 24.4% of the smokers, with 6.7 fold higher risk than the nonsmokers. The serum Cu concentrations of the smokers were significantly higher (102.4 ± 17.5 μg/dl) than the nonsmokers (70.7 ± 17.1 μg/dl), (P < 0.0001). Each 1 year decrease in the initial age of starting smoking was associated with an increase in the serum Cu concentration by 0.016 μg/dl. Each increase in the serum Cu concentration by 1 μg/dl was associated with a decrease in the serum Zn and Mg concentrations by 0.4 μg/dl and 4 μg/dl, respectively. Conclusion: Cigarette smoking is a significant risk factor for hypozincemia, hypomagnesemia, and high Cu concentrations regardless of the nicotine dependence status of the smokers. Early management of hypozincemia may be a preventive measure to decrease the incidence of the oxidative stress-induced diseases.

Keywords: Copper, magnesium, nicotine dependence, smoking, zinc

How to cite this article:
Mohammed AM, Hashish AF, El-Saeed GS. Studying the association between cigarette smoking and serum copper, zinc, and magnesium concentrations: A cross-sectional study. J Public Health Prim Care 2023;4:42-7

How to cite this URL:
Mohammed AM, Hashish AF, El-Saeed GS. Studying the association between cigarette smoking and serum copper, zinc, and magnesium concentrations: A cross-sectional study. J Public Health Prim Care [serial online] 2023 [cited 2023 Jun 5];4:42-7. Available from: http://www.jphpc.org/text.asp?2023/4/1/42/369664

Introduction

Tobacco smoking is one of the biggest public health threats worldwide. Every year, it kills more than 8 million people. More than 80% of tobacco users live in low- and middle-income countries such as India and Egypt.^[1] Smoking damages almost every organ in the body, and more than 16 million Americans live with smoking-related illnesses. For every person who dies as a result of smoking, at least 30 persons live with serious smoking-related illnesses.^[2]

Zinc (Zn), magnesium (Mg), and copper (Cu) are examples of the essential trace elements which serve as cofactors in various functions of the body. They are present as a component of nutrients and constituents of enzymes, vitamins, hormones, and other processes that maintain health. Zn is an important factor in maintaining the normal structure of cells and is actively involved in protecting the body from oxidative stress as it is a component of antioxidant enzymes.^[3] The impairment in serum concentrations of Zn in smokers may cause a long-term negative health effects.^[4] Zn can influence the nicotinic receptors stimulation and may works also as a modulator for the intensity of tobacco addiction.^[5]

On the other hand, the Mg plays an important role in the function of the central nervous system as well as in nicotine dependence.^[6] The key to addiction is increased dopaminergic and glutamatergic activity in the reward system.^[7] The stimulation of the N-methyl-d-aspartate (NMDA) receptor causes the release of dopamine and plays the most important role in nicotine dependence.^[8] Mg is a potent inhibitor of the NMDA receptor complex and this inhibition depends on the Mg concentration. It has been suggested that early treatment of hypomagnesemia in young people could reduce the initiation of smoking.^[9]

Several studies have documented that smoking can increase oxidative stress and impair oxidative defense systems, especially antioxidant enzymes contributing to cardiovascular diseases and cancer.^[4],[9] Both Zn and Cu are very important cofactors of the antioxidant enzyme, superoxide dismutase (SOD).^[10] An impairment in the serum concentration of one of the two elements will disturb the production of SOD. It has been reported that cigarette smoking decreases the appetite and may decrease the consumed amount of nutrients by smokers.^[4] In addition, tobacco leaves contain a significant amount of cadmium which is absorbed into the body when a person smokes or chews tobacco. This cadmium can replace the bivalent metals such as Zn and Cu.^[11]

Based on the literature survey, the studies conducted to investigate the relationship between cigarette smoking and trace elements alterations are insufficient. From about 24,000 articles and reviews indexed in databases on smoking cessation only less than 10 are focused on Mg, Zn, Cu, and other bivalent cations influence on nicotine addiction or tobacco smoking.^[7] Moreover, the relationship of the serum concentrations of these elements with the nicotine dependence has not been studied previously. The present study was designed to assess the relationship of serum Zn, Mg, and Cu concentrations with smoking as well as with nicotine dependence.

Subjects and Methods

Study design

A cross-sectional study was carried out totally on 85 male subjects, of which 41 adult male active cigarette smokers were matched by age, gender, and body mass index (BMI) to another 44 adult male nonsmokers as a control group. None of the recruited subjects were on mineral dietary supplements in the previous 6 months. In addition, the smokers who have any renal or hepatic impairment were not recruited in the study. Smokers were interviewed to fill a pretested questionnaire form included the personal history, smoking characteristics, and Fagerstrom test for nicotine dependence questionnaire (FTND). FTND is an 8-item questionnaire with a total score ≥8 indicative of high nicotine dependence. The Pack-Year Index has been calculated as mentioned in Metwally and Mohammed in 2016.^[12] Anthropometric measurements including weight (Kg) and height (cm) were assessed, and calculated BMI (Kg/m²) through dividing the individual's weight by the square of his height (m²).^[13] Before conducting the study, an ethical clearance has been obtained in accordance with Helsinki's Declaration, world medical association, 2013.

Laboratory assays

Assay of the urinary cotinine creatinine ratio

A urinary cotinine concentration was assayed by enzyme-linked immunosorbent assay (ELISA), a colorimetric method, using A commercial cotinine ELISA kits (Sigma-Aldrich, Co. LLC., USA). The manufacturer's guidelines had been followed and the results are expressed as Pg/ml
A urinary creatinine concentration was assayed by the colorimetric, alkaline picrate method (Jaffe), using A commercial creatinine colorimetric assay kits (Cayman, USA)
Correction of cotinine concentration for creatinine excretion through the calculation of cotinine:creatinine ratio.

Assay of serum zinc, copper levels

Serum Cu and Zn ions were assayed using the Agilent 5100 Synchronous Vertical Dual View by the inductively coupled plasma atomic emission spectroscopy, with the Agilent Vapor Generation Accessory 77. All samples were digested to have an acceptable matrix for measuring Zn, and Cu ions and to provide acceptable and consistent recovery compatible with the analytical method of Kumar et al.^[14] For each series of measurements, the intensity calibration curve was constructed composed of a blank and three or more standards from Merck Company (Germany). Accuracy and precision of Zn and Cu ion measurements were confirmed using external reference standards from Merck, and standard reference material and quality control sample from the National Institute of Standards and Technology, were used to confirm the instrument reading.

Assay of serum magnesium

Serum Mg was assayed using the automated clinical chemistry analyzer (Olympus AU 400 analyzer).

Statistical analysis

Data analysis was performed using the IBM SPSS version 20.0 software (SPSS Inc., Chicago, IL, USA). Quantitative data were expressed as mean ± standard deviation. Student's t-test was used to compare between two groups of normally distributed variables. The linear correlation between two individual variables was examined using Pearson correlation coefficient (r) and linear regression analysis. Logistic regression analysis was used and the unadjusted odds ratio with 95% confidence interval was determined. The p-values ≤0.05 were considered significant.

Results

The total mean age of the 85 male subjects of the study was 42.2 ± 9.7 years old. The Smokers' characteristics are summarized in [Table 1]. As shown in [Table 2], the mean serum Cu concentration was significantly higher among the smokers in comparison to their control group. On the contrary, the mean serum Zn and Mg concentrations were significantly lower among the smokers than that of controls. In [Table 3], there are 34.1% of the smokers versus 9.1% of the nonsmokers have Zn deficiency (i.e., hypozincemia), where the serum Zn concentration was <40 μg/dl. The risk of hypozincemia among the smokers was 5 folds higher than the nonsmokers (P = 0.008). Similarly, there are 24.4% of the smokers versus 4.6% of the nonsmokers have Mg deficiency (i.e., hypomagnesemia) where the serum Mg concentration was <1.5 μg/dl. Further, the risk of hypomagnesemia among the smokers was 6.7 folds higher than the nonsmokers (P = 0.02). No significant linear correlation could be detected between the Fagerstrom nicotine dependence score (FNDT) and any of the studied trace elements; serum Zn, Cu, and Mg (P > 0.05) as illustrated in [Figure 1], [Figure 2], [Figure 3]. There was a significant negative linear correlation between the initial age of starting smoking and the serum Cu concentration. The linear regression analysis revealed that each decrease in the initial age of smoking by 1 year was associated with an increase in the serum Cu concentration by 0.16 μg/dl as illustrated in [Figure 4].

Table 1: Summary for the smoker’s characteristics

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Table 2: Trace elements status of the studied smokers and nonsmokers control subjects

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Table 3: The risk of hypozincemia and hypomagnesemia in the smokers and nonsmokers

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Figure 1: Correlation between nicotine dependence score and serum zinc concentration

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Figure 2: Correlation between nicotine dependence score and serum magnesium concentration

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Figure 3: Correlation between nicotine dependence score and serum copper concentration

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Figure 4: Correlation between initial age of smoking and serum copper concentration

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No significant linear correlation could be detected between any of the studied trace elements and any of the other smoking parameters (P > 0.05). Moreover, significant negative linear correlations were detected between the serum Cu concentration and both serum Zn concentration and serum Mg concentration. The linear regression analysis model showed that each increase in the serum Cu concentration by 1 μg/dl was associated with a decrease in serum Zn and Mg concentrations by 0.4 μg/dl and 4 μg/dl, as illustrated in [Figure 5] and [Figure 6], respectively.

Figure 5: Linear correlation between the serum copper and serum zinc concentrations

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Figure 6: Correlation between the serum copper and magnesium concentrations

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Discussion

Tobacco smoking is a significant risk factor for developing several diseases. Several explanations have been postulated in the previous studies to explain the smoking-induced effects. Based on the literature review, the relationship between smoking, including nicotine dependence, and the serum Zn, Cu, Mg status has not been studied sufficiently.

The present study revealed markedly lower serum Mg (1.83 ± 0.4 μg/dl) and Zn (50.9 ± 13.6 μg/dl) concentrations among the smokers than that observed among the nonsmokers (2.06 ± 0.3 and 82.6 ± 27.8 μg/dl, respectively) [Table 2]. Moreover, hypozincemia (serum Zn <40 μg/dl) has been detected among 34.1% of the smokers and the risk of developing hypozincemia among the smokers was 5 times higher than the nonsmokers. In addition, hypomagnesemia (serum Mg <1.5 μg) was detected among 24.4% the smokers with 6.7-fold more at risk than the nonsmokers [Table 3].These findings may have been resulted from deficient dietary intake among the smokers as a result of tobacco-induced decreased appetite and decreased consumed amounts of nutrients by smokers. It may be also due to deficient absorption of Zn and Mg; caused by a tobacco chelating effect. Furthermore, cigarette smoking has been shown to be a factor that can increase cadmium levels to an extent that significantly increase Zn excretion.^[15] Anyway, Bloomer, in 2007,^[16] reported that even though dietary intake of minerals in smokers was adequate, the habitual diet was not able to maintain the serum Zn concentration in the normal ranges, and thus making them more susceptible to diseases. On the contrary, the serum Cu concentration showed significantly higher levels among the smokers (102.4 ± 17.5 μg/dl) than that detected among the nonsmokers (70.7 ± 17.1 μg/dl) [Table 2]. This finding is in agreement with the previous studies which reported a significantly higher serum Cu concentration among the smokers, as compared to nonsmokers^[4],[17] [Table 2]. Mussalo-Rauhamaa, et al., in 1986^[18] Studied the cigarettes as a source of some trace and heavy metals in man and reported that the Cu content in tobacco leaves was 15.6, g/g. Smoking apparently increases the serum Cu levels from 1.14 mg/l in nonsmokers to 1.21 mg/l in light smokers, and 1.31 mg/l in smokers of more than 10 cigarettes/day.^[19]

A significant inverse linear correlation was detected between the serum Cu concentration of the smokers and their initial age of starting smoking. In this study, it is predicted that each decrease by 1 year in the initial age of starting smoking, will increase the serum Cu concentration by 0.16 μg/dl [Figure 4]. This finding may be due to increased number of years of tobacco exposure and enhances the prohibition and criminalization of smoking in children and adolescents. The previous studies found that the higher serum concentration levels of Cu causes problems with the function of the kidneys, liver, and cardiac muscle and damages the central nervous system with manifestation of mental symptoms.^[20],[21] However, fortunately, the elevated Cu levels among the smokers in our study were within the normal range of the laboratory reference values (50–140 μg/dl), i.e., no cases of hypercupremia were detected in the study. We detected also an inverse linear correlation between the serum Cu concentration, and the serum Zn and Mg concentrations. We found that each increase in the serum Cu concentration by 1 μg/dl was associated with a decrease in the serum Zn concentration by 0.4 μg/dl and a decrease in the serum Mg concentration by 0.004 mg/dl (i.e., 4 μg/dl) [Figure 5] and [Figure 6].

As regards the nicotine dependence, we could not detect any significant correlation between the nicotine dependence status of the smokers; based on the Fagerstrom nicotine dependence test score (FTND); and the serum Zn, Mg, and Cu concentrations [Figure 1], [Figure 2], [Figure 3]. However, It is reported that the alpha-3 beta-2 (α3 β2) nicotinic receptors are inhibited by Zn, and α4 β2, α2 β4 receptors exhibited a biphasic modulation by Zn.^[5] Thus, the early detection and treatment of the hypozincemia in the smokers may decrease and modulate the intensity of nicotine dependence.

This study has few limitations; the sample size of the study was relatively small (n = 85) and larger scale study is recommended. However, the study demonstrated significant associations between cigarette smoking and hypozincemia, hypomagnesemia, and hypercupremia. Further, the correlation between the initial age of starting smoking and the hypercupremia has not been studied previously.

Conclusion

Based on the results of the study, it is concluded that cigarette smoking is a significant risk factor for hypozincemia and hypomagnesemia regardless of the nicotine dependence status of the smokers. A significant higher serum Cu concentration was detected among the smokers and it was inversely correlated with the serum Zn, Mg concentrations, and the initial age of starting smoking. Early detection of these impairments through routine investigation in primary health-care settings and early management of the hypozincemia in the smokers through dietary supplementations may be a preventive measure to avoid or decrease the incidence of the oxidative stress-induced diseases. Moreover, treating the hypomagnesemia and hypozincemia may modulate the intensity of nicotine dependence and help in smoking cessation programs. Smoking at an early age is a significant risk factor for higher serum Cu concentrations and consequently, for more oxidative stress-induced diseases. Hence, the role of health education and the brief opportunistic advice in health-care facilities by primary health-care providers is critical as a primary preventive measure.

Acknowledgment

The authors would like to thank the National Research Centre, Egypt, for the great help and support to complete this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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