|Year : 2020 | Volume
| Issue : 1 | Page : 4-12
The role of copper and zinc in the prevention of dental caries - A systematic review
Ambar Khan, Basavaraj Patthi, Ashish Singla, Ravneet Malhi, Divyangi Goel, Monika Kumari
Department of Public Health Dentistry, D.J. College of Dental Sciences and Research, Modinagar, Uttar Pradesh, India
|Date of Submission||25-Jun-2019|
|Date of Decision||26-Aug-2019|
|Date of Acceptance||13-Jan-2020|
|Date of Web Publication||2-Mar-2020|
Department of Public Health Dentistry, D.J. College of Dental Sciences and Research, Modinagar, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Dental caries is one among the major public health problems and has been found to have a multifactorial etiology. Thus, understanding the role of trace elements such as Copper and Zinc in the prevention of dental caries is of utmost importance to the clinicians. The aim is to systematically review the literature on the role of Copper and Zinc in the prevention of Dental Caries. A literature review was performed in PubMed Central and Cochrane library, and Embase, Google Scholar were searched up to February 2019 to identify appropriate studies. Randomized controlled trials and crosssectional studies assessing the role of copper and zinc in the prevention of dental caries in the adult and pediatric population searched above were included. The methodological quality was assessed using a five and sevenpoint ordinal scale, respectively. The search was performed from 1990 to February 2019 for all the mentioned databases. There was no lower limit for the analyzed time frame and no language restrictions. In the various articles available through the electronic database, eight articles fulfilled the inclusion criteria and were selected for the review. The primary outcome measure was salivary concentrations of copper and zinc in caries free and caries active individuals as measured by the World Health Organization (1997) decayed, missing, and filled teeth/decayedextractedfilled teeth index. The limitations were that it cannot definitely establish the negative correlation of salivary concentrations of copper and zinc with caries activity due to the lack of studies done on these trace elements and the inconsistency of the data found in the existing literature. Of the total 58 articles which were searched, 8 articles fulfilled the criteria and were selected for the review. One article which was received through email was also included. It was found that the amount of copper and zinc in low carious individuals is high, whereas it is low in cases of high caries individuals. Copper and zinc have a negative correlation with dental caries activity. There are relatively few studies evaluating the role of Copper and Zinc in the prevention of dental caries. By analyzing the elements affecting caries activity, it can be derived that copper and zinc have a negative effect on the dental caries process.
Keywords: Copper, dental caries, diet, trace elements, zinc
|How to cite this article:|
Khan A, Patthi B, Singla A, Malhi R, Goel D, Kumari M. The role of copper and zinc in the prevention of dental caries - A systematic review. J Indian Assoc Public Health Dent 2020;18:4-12
| Introduction|| |
Dental caries is a multifactorial disease involving a complex interplay among a number of factors in the oral environment which include the host, diet, time, and the microbial flora. The development of caries requires both the presence of bacteria and fermentable carbohydrates.Streptococcus mutans and Streptococcus sobrinus, two species of the Mutans streptococci, are the most significant microorganisms found in human caries. Deep, narrow occlusal fissures and lingual and buccal pits tend to trap food debris and bacteria, which can cause tooth decay. The interdental areas and malalignment of the teeth, such as crowding and unusual spacing can upsurge the vulnerability to caries.,,, The role of refined carbohydrates, especially the disaccharide sucrose, in the etiology of dental caries is well established. The quantity of sugar ingested, its oral clearance rates, and frequency of consumption is an important factor in the etiology.,,,, While there have been continuous efforts to reduce its prevalence, dental caries remains to be the most common chronic disease affecting human beings since ages. It is ubiquitous in all populations worldwide, and is the prime factor responsible for dental pain and tooth loss. Thus, it is considered to be one of the world's major public health problems.
Saliva is composed of about 99% water and 1% solids; 0.5% inorganic substances (chloride, sodium, phosphorus, calcium, potassium, nitrogen, oxygen, bicarbonate, dissolved carbon dioxide, and trace elements) and 0.5% organic substances (protein, vitamin, lipid, hormone-like substance, free amino acid, urea, microbial, shed cells, and antimicrobial substances). Studies have shown that the organic and inorganic constituents of saliva play an essential role in the caries process besides other physiological functions. Elements that are present only in minute quantities in animal tissues are called trace elements regardless of their abundance in nature. Some of these, such as fluoride (F), iron (Fe), iodine (I), copper (Cu), zinc (Zn), manganese (Mn), and molybdenum (Mo) are physiologically essential for the various bodily functions. These trace elements form an important composition of the enamel. The enamel contains elements such as fluoride (F), potassium (K), copper (Cu), zinc (Zn), sodium (Na), magnesium (Mg), iron (Fe), lead (Pb), strontium (Sr), and other minor ionic components as trace elements. Deficits in these trace elements such as fluoride, copper, zinc, and iron content of the enamel are accomplices with progressive caries.
Among these elements, copper and zinc are the potential components related to the formation of and changes within the enamel matrix. The majority of zinc is accumulated in teeth directly after their eruption, and protein binding is a mechanism that determines the zinc level. Zinc also interacts with hydroxyapatite through the absorption to the crystal surface and its incorporation in the crystal lattice. Low concentrations of this element modify or inhibit remineralization; however, they also significantly reduce enamel dissolution. On the other hand, copper has a significant impact on the acid solubility of enamel, which is a basic process in the development of dental caries and erosion. The dissolution of enamel is reduced in the presence of copper ions. The ability to precipitate a protective copper phosphate phase on the tooth surface decreases and inhibits demineralization through stabilization of the crystal lattice of enamel surface. Furthermore, copper exerts a cariostatic effect through inhibition of the bacterial growth and the various bacterial metabolic enzymes.
Despite considerable interest in trace element concentrations in the enamel as a determinant of dental caries, there have been comparatively few attempts to analyze the trace element composition of saliva. Even fewer studies have been attempted to correlate human caries susceptibility with the salivary concentration of copper and zinc. This is surprising because saliva constantly bathes the teeth and is important in the prevention and remineralization of early enamel caries. An understanding of the mineral components of saliva is, therefore, of great importance in the prevention of dental caries. Thus, this systematic review will be helpful to the clinicians in evaluating if copper and zinc in dental plaque and saliva have a role in the prevention of dental caries.
Does copper and zinc in plaque and saliva play a role in the prevention of dental caries among pediatric and adult population?
The study objective was to review the role of copper and zinc in the prevention of dental caries in the pediatric as well as adult population.
| Materials and Methods|| |
Search method for identification of studies
For the identification of the studies included in this review, we devised the search strategy for each database. The search strategy used a combination of controlled vocabulary and freetext terms, as follows: (((((“dental caries“ [MeSH Terms] OR (“dental“ [All Fields] AND “caries“ [All Fields]) OR “dental caries“ [All Fields]) AND (“copper“ [MeSH Terms] OR “copper“ [All Fields])) AND (“zinc“ [MeSH Terms] OR “zinc“ [All Fields])) AND (“prevention“ [Subheading] OR “prevention“ [All Fields] OR “prevention“ [All Fields] OR “prevention“ [MeSH Terms])). The main databases searched were PubMed, PubMed Central, Cochrane Review, Embase, and Google Scholar [Figure 1]. All the articles which were published in English, dated from the year 1980 to February 2019 were included in this review.
- PubMed (1980–2019)
- PubMed Central (1980–2019)
- Cochrane Library (1980–2019).
- Embase (1980–2019).
- Google Scholar (1980–2019).
The search terms for articles were the terms either mentioned in the title or abstract. Full-text original research articles were taken. Unpublished articles in press and personal communications, etc., were screened and excluded. Our focus was to be broad in scope to include as much relevant existing data as reasonably possible.
- Original research articles
- In vivo human studies
- Randomized controlled trials (RCTs)
- Cross-sectional studies
- Studies emphasizing the effective role of copper and zinc in the prevention of dental caries.
- Narrative review articles
- Case series, case reports and letters to the editor
- The articles for which the results were inconsistent
- Unpublished articles in the press.
Types of outcome measures
Salivary concentrations of copper and zinc in caries free and caries active individuals as measured by the World Health Organization (1997) decayed, missing, and filled Teeth/decayed-extracted-filled teeth index is the primary outcome measure to be assessed. The following secondary outcomes were considered relevant: decrease in plaque pH and acidogenicity of the plaque biofilm.
Data analysis and extraction
Any duplicates from the gathered results were eliminated and the remaining articles were examined by the title and abstract. Subsequently, the full texts were obtained and analyzed for further inclusion/exclusion. Studies that did not meet the inclusion criteria were excluded. The full-text articles of those identified after the title and abstract were screened. All the included studies were assessed for the study design characteristics and features of internal validity. An instrument was developed to assess the quality of the eligible studies. Each study was assessed in terms of study settings, sampling strategy, measurement tools, analysis method, and generalizability of findings. For RCTs and cross-sectional studies, there are five- and seven-point ordinal scale indicators, respectively, for quality assessment, which were assessed using the Cochrane Risk of Bias Tool for RCTs and the Quality Assessment Tool for Systematic Reviews of Observational studies. For every included study, the study definition, risk of bias assessment, total length of study, unit of randomization, unit of analysis, participants' characteristics, interventions, outcomes, results, and other items were collected and analyzed.
The search also included one original article obtained through e-mail from contact with an expert which completely fulfilled the inclusion criteria for this review.
The search strategy for PubMed is described in [Figure 1]. Thus, a total of 08 full-text articles which attempted to assess the role of copper and zinc in dental caries, were retrieved for the review. Reported data were analyzed and represented in the form of figures and tables for the current review.
Synthesis of findings
The absence of significant clinical heterogeneity in terms of patient demographic characteristics and the measures used to record dental caries, along with the quality of the studies, led to the decision to pool the study data. Because clinical heterogeneity was high, the summarized findings were depicted qualitatively only without meta-analysis.
| Results|| |
By following the described strategy, the electronic search yielded 58 articles, and texts of the 52 articles which seemed to be relevant were obtained and reviewed after the removal of duplicates. Based on the title of the study, 28 articles were excluded and the remaining 24 were screened. After abstract evaluation, 18 full-text articles got eligible for the review. According to the inclusion criteria, a total of eight studies, which attempted to assess the role of copper and zinc in dental caries, were selected for the review [Figure 1]. The overall summary of all the RCTs and cross-sectional studies is described in [Table 1].
In the RCTs conducted by Afseth et al.,,, a significant reduction in acid production was found in plaque challenged with glucose solutions containing 0.25 mM Copper sulfate, or 5.0 mM Zinc acetate as compared to glucose solutions alone. Neither 0.1 mM copper sulfate nor 2.5 mM Zinc acetate reduced the acidogenicity of plaque significantly, whereas a combination of these sub-effective concentrations was effective. A rinse with the copper salt solution significantly depressed acid formation in plaque for a period of 6 h, whereas a rinse with the zinc solution was effective for 2 h. Plaque concentrations of the metals increased from <75 ppm to more than 1000 ppm 2 h after a rinse with the metal salts. 12 h after a rinse the mean plaque concentrations were 190 ppm copper or 358 ppm zinc, respectively. A significant reduction (P < 0.05) in acid formation was seen in plaque exposed to five subsequent rinses. The mean amounts of copper and zinc in plaque increased more than 10-fold after five rinses. It was concluded that these metals are retained in plaque and that their concentrations in plaque increase with repeated applications.
While in the study conducted by Duggal et al., copper was found to have a consistent, inverse relationship with caries experience. On the other hand, the concentration of zinc in saliva did not seem to have any consistent relationship with the caries experience in the children. While in the study done by Hussein et al., Salivary copper and zinc levels were found to be significantly higher in children with dental caries compared to those who remain caries-free (P < 0.05). Moreover, these elements had a positive correlation with dental caries and showed significant differences between caries and caries-free groups. In the study done by Hegde et al., the mean copper and zinc levels were found to be lower in the caries-free group than in the caries-active group and was found to be statistically significant (P < 0.0001). In the study conducted by Bhandary et al., it was revealed that the amount of copper and zinc in saliva of low caries individuals was higher than the high carious individuals. Zinc was found to have a high significant value (0.005), whereas copper was not found to be so significant (0.478). Hence, it is concluded that copper and zinc have a negative correlation with dental caries, but only zinc had a significant effect. The study by Hussein et al. demonstrated higher levels of zinc and copper in caries-free children compared to that in children with early childhood caries (ECC). Thus, a negative correlation was observed in salivary zinc and copper, while the correlation in children with ECC.
Risk of bias in included studies
The included RCTs were evaluated for random sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting to assess the risk of bias. These studies conducted by Afseth et al.
, Afseth, Afseth et al. were at high risk for random sequence generation; unclear for allocation concealment; at low risk for blinding of outcome assessment, incomplete outcome data addressed and selective outcome reporting [Table 2].
Differences between baseline and end-of-trial scores for parameters of interest are shown in [Table 3] and [Table 4].
|Table 3: Acid formation in dental plaque at time intervals after a rinse with a metal salt solution|
Click here to view
The studies conducted by Afseth et al.
, Afseth, Afseth et al., presented baseline data and end of trial scores with respect to changes in time within each group [Table 3] and [Table 4]. From these three studies, the general trend was found to be that mouth-rinsing with varying concentrations of copper and zinc solutions, showed significant change between baseline and end of the trial score for all evaluated parameters.
| Discussion|| |
Human saliva is a unique secretion of major and minor salivary glands to maintain normal physiological functions of oro-biological structures. Saliva is the first line of defense against dental caries. Hence, it is very important to understand the physiochemical nature of saliva to use its beneficial effect to combat dental caries. The saliva contains a lot of organic and inorganic substances. Apart from these, there are a few elements which are present in very minute quantity but play a significant role in maintaining the health of the teeth. They are known as trace elements. These are present in biological substances and fluid in amounts as low as microgram per gram or less in concentration. The composition of saliva is potential of great importance to the prevention of caries. The relationship of trace elements such as copper and zinc, in the saliva to dental caries activity, has interested scientists for many years. Conflicting reports from researchers who have investigated copper and zinc in saliva indicate that the nature of the role that these elements play in the carious process remains undefined. An intimate and perhaps significant relationship between copper and zinc and the number of decayed tooth surfaces has been reported.
It has been observed that Cu2 + and Zn2 + inhibit acid formation in the plaque biofilm. There seems to be an inverse correlation between the metal content and acid formation in plaque. It has been found that acid production in dental plaque following a mouth rinse with copper sulfate or zinc acetate was significantly lower. A much smaller concentration of the metal ions was needed to obtain a significant effect on the acidogenicity of plaque. The pH values are also found to be significantly reduced following copper and zinc mouth rinses. However, the concentrations of copper and zinc in plaque were markedly elevated even 12 h after a mouth rinse. The long retention time indicates a relatively strong binding of these metals in the plaque. It seems possible that the acidogenicity is only affected when the metal concentration in plaque is above a certain critical level. These findings have been supported by RCTs conducted by Afseth et al.
, Afseth, Afseth et al. It is thus concluded that the increased concentration of zinc and copper in plaque helps in reducing the acid formation and thus, helps in the prevention of dental caries.
Copper and zinc seem to have a direct relationship with dental caries activity. The salivary concentration of copper and zinc is found to be different in caries-free and caries active individuals. The cross-sectional studies conducted by Duggal et al. and Bhandary et al. supports that the salivary concentrations of copper and zinc were found to be significantly low in the high caries activity group. While in a study done by Hussein et al., the salivary concentrations of copper and zinc were found to be low in children with ECC as compared to children who were Caries free.
Interestingly, similar cross-sectional studies conducted by Hussein et al. and Hegde et al. support that the salivary concentrations of copper and zinc were found to be significantly high in the high caries activity group. This could be attributed to the possibility of tiny amounts of copper and zinc present in the tooth dissolving into the saliva by demineralization, thereby resulting in the increased levels in the mixed saliva.
The findings of these studies are inconsistent with each other, and these variations have been explained on the fact that the studies have been conducted on a very small sample population. Studies on a larger number of subjects might contribute more to an understanding of the relationship between low concentrations of copper and zinc in oral fluids and individual caries experience. Thus, the limitations of the systematic review were that it cannot completely establish the negative correlation of salivary concentrations of copper and zinc with caries activity. This can be attributed to the lack of studies done on these trace elements and the inconsistency of the data found in the existing studies. However, even with the limited literature available at present regarding the role of copper and zinc in dental caries, it can be said that copper and zinc seem to have a significant negative correlation with caries activity and their reduced salivary concentrations are an indicative of increased caries activity.
| Conclusion|| |
The present systematic review revealed that the amount of copper and zinc in low carious individuals is high, whereas it is low in cases of high caries individuals. Copper and zinc have a negative correlation with dental caries activity. This implies that zinc and copper have a negative effect on the dental caries process. Dental caries is one among the major public health problems. Understanding the etiology and factors affecting dental caries activity requires a multidisciplinary approach. By analyzing the elements affecting caries activity, it can be derived that these elements (copper and zinc) can be incorporated into oral supplementation and applications such as mouth rinse and toothpaste to produce an inhibitory effect on caries activity and beneficial effect on tooth structures.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Klimuszko E, Orywal K, Sierpinska T, Sidun J, Golebiewska M. The evaluation of zinc and copper content in tooth enamel without any pathological changes – An in vitro
study. Int J Nanomedicine 2018;13:1257-64.
Babaahmady KG, Marsh PD, Challacombe SJ, Newman HN. Variations in the predominant cultivable microflora of dental plaque at defined subsites on approximal tooth surfaces in children. Arch Oral Biol 1997;42:101-11.
Dias da Silva PR, Martins Marques M, Steagall W Jr., Medeiros Mendes F, Lascala CA. Accuracy of direct digital radiography for detecting occlusal caries in primary teeth compared with conventional radiography and visual inspection: An in vitro
study. Dentomaxillofac Radiol 2010;39:362-7.
Liu F. The relation between the resistance distribution on crown surface and caries. Zhonghua Kou Qiang Yi Xue Za Zhi 1993;28:47-9.
Marcucci M, Bandettini MV. Dental caries in the rat in relation to the chemical composition of the teeth and diet. Variations in the diet of the CA/P ratio obtained by changes in the phosphorus content. Minerva Stomatol 1981;30:17-20.
Haldi J, Wynn W, Bentley KD, Law ML. Dental caries in the albino rat in relation to the chemical composition of the teeth and of the diet. IV. Variations in the CA/P ratio of the diet induced by changing the calcium content. J Nutr 1959;67:645-53.
Burt BA, Eklund SA, Morgan KJ, Larkin FE, Guire KE, Brown LO, et al
. The effects of sugars intake and frequency of ingestion on dental caries increment in a three-year longitudinal study. J Dent Res 1988;67:1422-9.
Caldwell RC. Physical properties of foods and their caries-producing potential. J Dent Res 1970;49:1293-8.
Harris, RS. Minerals: Calcium and phosphates. In: Gould RF, editor. Dietary Chemicals Versus Dental Caries, Advances in Chemistry Services. Vol. 94. Washington (DC): American Chemical Society; 1970. p. 116-22.
Nizel, AE. Nutrition in Preventive Dentistry: Sciences and Practice. 2nd
ed. Philadelphia (PA): WB Saunders; 1981. p. 417-52.
Muchhal M, Niraj LK, Chaudhary D, Ali I, Dhama K, Patthi B. Spanning the horizon of accuracy of different intraoral radiographic modalities: A systematic review. J Contemp Dent Pract 2017;18:1206-12.
Lee Y. Diagnosis and prevention strategies for dental caries. J Lifestyle Med 2013;3:107-9.
Hussein AS, Ghasheer HF, Ramli NM, Schroth RJ, Abu-Hassan MI. Salivary trace elements in relation to dental caries in a group of multi-ethnic schoolchildren in Shah Alam, Malaysia. Eur J Paediatr Dent 2013;14:113-8.
Weatherell JA. Composition of dental enamel. Br Med Bull 1975;31:115-9.
Duggal MS, Chawla HS, Curzon ME. A study of the relationship between trace elements in saliva and dental caries in children. Arch Oral Biol 1991;36:881-4.
Joanna Briggs Institute. The Joanna Briggs Institute Critical Appraisal Tools for use in JBI Systematic Reviews: Checklist for Qualitative Research. Australia: The Joanna Briggs Institute; 2016.
Afseth J, Oppermann RV, Rolla G. The in vivo
effect of glucose solutions containing Cu++ and Zn++ on the acidogenicity of dental plaque. Acta Odontol Scand 1980;38:229-33.
Afseth J. Some aspects of the dynamics of Cu and Zn retained in plaque as related to their effect on plaque pH. Scand J Dent Res 1983;91:169-74.
Afseth J, Oppermann RV, Rølla G. Accumulation of Cu and Zn in human dental plaque in vivo
. Caries Res 1983;17:310-4.
Hegde MN, Hegde ND, Ashok A, Shetty S. Biochemical indicators of dental caries in saliva: An in vivo
study. Caries Res 2014;48:170-3.
Bhandary S, Shetty S, Shetty A, Hedge MN. Correlation of trace elements in saliva with dental caries activity. Int J Curr Res 2015;7:18574-7.
Hussein AS, Salih BA, Al-Nasir MG. The association of salivary calcium inorganic phosphorus zinc and copper in children and early childhood caries: A case-control study. J Oral Dent Res 2017;4:110-9.
Higgins JP, Altman DG, Sterne JA. Cochrane collaboration risk of bias tool: Assessing the risk of bias in included studies. In: Higgins JP, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Ch. 8. New Jersey, United States: John Wiley and Sons, The Cochrane Collaboration; 2011.
[Table 1], [Table 2], [Table 3], [Table 4]