|Year : 2014 | Volume
| Issue : 2 | Page : 100-104
Trace elements in oral health and disease: An updated review
Noopur Kulkarni1, Ketki Kalele1, Meena Kulkarni1, Rahul Kathariya2
1 Department of Oral Pathology and Microbiology, Dr. D Y Patil Dental College and Hospital, Dr. D Y Patil Vidyapeeth, Pune, Maharashtra, India
2 Department of Periodontics and Oral Implantology, Dr. D Y Patil Dental College and Hospital, Dr. D Y Patil Vidyapeeth, Pune, Maharashtra, India
|Date of Web Publication||5-Jun-2014|
Department of Periodontics and Oral Implantology, Dr. D Y Patil Dental College and Hospital, Dr. D Y Patil Vidyapeeth, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Enzymes of trace elements are an important part of certain biological and chemical reactions. They work in harmony with proteins and often with certain other co enzymes. They attract substrate molecules and enable their conversion to a specific end product. Some trace elements are involved in redox reactions. Modern day diet, comprising of refined foods is a cause of concern, as it may not have a sufficient amount of these trace elements. Dietary supplements may be of required to combat this shortage. The present paper has thoroughly discussed trace elements, as this area of research has not received the deserved attention. Thus, a comprehensive understanding of these trace elements is essential and significant for disease control and for maintaining optimal health.
Keywords: Health, micro-nutrients, trace elements
|How to cite this article:|
Kulkarni N, Kalele K, Kulkarni M, Kathariya R. Trace elements in oral health and disease: An updated review. J Dent Res Rev 2014;1:100-4
|How to cite this URL:|
Kulkarni N, Kalele K, Kulkarni M, Kathariya R. Trace elements in oral health and disease: An updated review. J Dent Res Rev [serial online] 2014 [cited 2019 May 20];1:100-4. Available from: http://www.jdrr.org/text.asp?2014/1/2/100/133959
| Introduction|| |
The human body contains elements that can be classified as abundant elements and trace elements. Abundant elements are those that are involved in the formation of covalent bonds, which are important constituents of tissues and semi-major elements, which often exist in the ionic state, and are involved in functions of the living body through maintenance of osmotic pressure and membrane potentials. 
Trace elements or micro-nutrients are chemical elements required in minute amounts, usually as part of a vital element. There are 19 trace elements divided into three groups (WHO classification):
- Essential elements
- Probably essential elements
- Potentially toxic elements. 
Essential trace element include zinc (Zn), copper (Cu), selenium (Se), chromium (Cr), cobalt (Co), iodine (I), manganese (Mn), and molybdenum (Mo). Although they account for only 0.02% of the total body weight, they play a significant role. As each trace element is related to many enzymes, deficiency of one trace element is not associated with any specific clinical presentation, but rather presents as a combination.
| Biological Significance of Trace Elements|| |
Enzymes of trace elements are an important part of certain biological and chemical reactions. They work in harmony with proteins and often with certain other co enzymes. ,,,,
They attract substrate molecules and enable their conversion to any specific end product. Some trace elements are involved in redox reactions; e.g. in the burning of food products. Some have structural roles by helping to impart stability and three-dimensional structures to vital biological molecules.
| Homeostat of Trace Elements|| |
When an essential trace element is absent or is not available in adequate quantities, it might lead to life-threatening consequences. Homeostatic regulation is a process involving absorption, storage, and excretion. The relative importance of these three processes is significantly different among each of these trace elements.  The amount absorbed from the gastrointestinal tract, often is the center for the controlling mechanism for cationic elements that is copper, iron, and zinc. The daily dietary requirements of trace elements are tabulated in [Table 1]. Excretions occurring through sweat, urine, bile, and breathe is a major mechanism for controlling the quantity of these elements in any organisms. To prevent adverse reactions, some of these elements are stored in inactive forms when available in excess quantities.
|Table 1: Daily dietary requirements of trace elements in adult males (body weight: 50 kg) |
Click here to view
| Factors Affecting Trace Elements Requirement|| |
Though trace elements play a vital role in a variety of processes needed for life, the occurrence of their deficiencies of any of the trace elements is relatively uncommon due to the strong homeostatic mechanisms. However, there are situations that may make a trace element nutritionally valuable. ,
Recently, Tapp and Natelson have presented a formula.
Pathological effects = Organic Vulnerability × Stress
This formula seems quite applicable to trace element nutrition.
| Trace Elements and Nutrition|| |
Our diet today, comprises of refined food. This is a cause of concern to a modern man as he may not be receiving sufficient amount of trace elements in his food sources, and dietary supplements may be of usage in combating this shortage. The interactions of micro-nutrients are difficult to study, since; they occur together in various forms and amounts; their absorption from the intestinal tract may be exclusively dependent on their relative concentrations; they can be synergetic or antagonistic; the amount could depend on the other essential trace elements in the diet.
Essential nutritional elements
decide if a micro-nutrient is "essential" or not, a wide variety of criteria are applicable, such as, the presence of the nutrient in a living healthy tissue, if it is seen in the fetus and neonates and if the body maintains its equilibrium control over its uptake in the hematopoietic stream or tissue and its excretion. 
The following list is considered as essential micro-nutrients: ,,
Cobalt, copper, chromium, fluorine, iron, iodine, manganese, molybdenum, selenium, and zinc. Nickel, tin, vanadium, silicon, and boron have off late been found to be important as micro-nutrients, Aluminum, arsenic, barium, bismuth, bromine, cadmium, germanium, gold, lead, lithium, mercury, rubidium, silver, strontium, titanium, and zirconium are all found in plant and animal tissue, but their importance is still being determined.
| Functions of Trace Elements|| |
Chromium is an important mineral for obese people, and it is one of the key minerals in controlling blood sugar and lipid levels. As the main ingredient of glucose tolerance factor (GFT), chromium helps insulin in reducing the blood glucose, by stimulating glucose uptake from the muscles and other tissues. When the chromium levels are less, the circulating level of (GFT) is less, and as a result, insulin is less effective in reducing blood sugar. Hence, blood sugar remains high, stimulating further insulin release, which is again blocked from being effective. ,,
Copper in its many forms is the third most abundant mineral in the body, apart from being important for many other enzymes. Copper is involved in the release process of energy inside the cell and contributes in the functioning of many antioxidants. The formation and regulation of hormones like melatonin is controlled by copper, via a wide range of neurotransmitters and other neuroactive compounds including the catecholamine's. Moreover, collagen production, formation of red blood cells and the oxidation of fats are dependent on copper concentration. Copper is also needed for the proper functioning of vitamin C and iron absorption. ,,,,
Zinc is a mineral with a wide application in human health. It is needed for a healthy immune system. It is also needed for cell division, hair, tissue, nails, skin, and muscle growth, synthesis of protein and collagen- which are needed for wound healing. ,,,,
Selenium salts are toxic in excess amounts, but trace amounts of selenium are needed for cellular functioning in many organisms. Interest in the biological role of selenium was centered on its action as an ingredient of the antioxidant enzymes glutathione peroxides and thioredoxin reductase. 
The most important role of molybdenum is sharing a common cofactor, molybdoprotein, at the active site in certain enzymes. Molybdoprotein is bound on molybdenum atom through adjacent sulfur atoms. In humans, a process of purine catabolism is catalyzed by a molybdenum containing enzyme. Molybdenum concentration also affects protein synthesis, the metabolism process, and growth of the body. 
The major role of iodine in nutrition arrives from the role it plays in thyroid hormones in regard to the growth and development of humans. The effects of iodine-deficiency on growth and development are denoted by iodine-deficiency disorders that are seen at all stages of development.
Iodine nutritional status can be assessed by means of goiter surveys, the determination of urinary iodine excretion, and the measurement of thyroid hormones and pituitary thyroid stimulating hormone. ,,
Manganese is an element that comprises only 0.00016% of the human body. It has a dual function as both an activator and a constituent of several enzymes in the body. ,,
Silicon the second most abundant element in the earth's crust, is not found free in nature, and occurs as oxides and silicates. It is present in the stroma of mammals probably giving them rigidity and strength. Plus, the essential role of silicon in the development of bone in two species of experimental animals has been documented. ,,
Nickel is not normally of biological interest. About 8% and 50% of nickel that is ingested in drinking water after an overnight fast is absorbed by humans, those results in marked hypernickelemia. In addition, contact dermatitis is the most important clinical effect of excess nickel exposure. ,,
There has been no opportunity to investigate possible indicators for a sufficient boron status. ,,
Vanadium is one of the least common elements and was not regarded as being of biological interest. However, in mammals the element has its beneficial effects on teeth, and hemopoiesis. ,,
Fluorine is only a minute part of the weight of man and enters the body by both drinking water and foods. Body fluoride status depends on multiple factors. ,,
A low level of fluorine in drinking water is connected to tooth decay. The dental tissue usually shows signs of toxicity, and mottling of tooth enamel is a well-known feature of excess fluoride ingestion. Long-term exposure to high levels of fluoride leads to dental decay. Further, in the body ionic fluoride rarely exists in blood, most ingested fluoride is trapped in the bone tissue.
Lead and mercury
Of the many dietary interactions influencing the uptake of lead or its retention with calcium are important. Defects in hemoglobin synthesis and lessened erythrocyte life span provide biochemical indication of lead exposure in the absence of clinically detectable signs. ,,
Cadmium uptake is increased in elderly people with depleting iron stores. Health risks are reported when the inhalation of cadmium from occupational sources results in lung damage. Cadmium retention in body tissues is related to the formation of, a cadmium protein complex of lower molecular weight.
Trace elements and carcinogenesis
There are various elements, both macro-nutrients and micro-nutrients that promote the process of carcinogenesis. The role of trace elements in the carcinogenecity of metals is evident in epidemiological surveys. The list includes several elements such as, iron, zinc, copper, cadmium, berilium boron and so on.
Potential of metals in carcinogenesis
Metal carcinogenesis has in recent times been attracting attention both in terms of occupational diseases and in ordinary environments. Several metals act in various ways in synchronization with each other to bring out regulatory mechanisms in the human body. Dysregulation of this equilibrium leads to uncontrolled adverse reactions in the body. The following is a list of various elements and its action on the body mechanism. ,
Sarcomas and skin cancers have been reported to have developed where intramuscular injections with iron dextran were used. Different malignant neoplasms of various organs are seen in idiopathic hemochromatosis, but liver cancer is a common complication. The mechanisms of carcinogenesis are thought to be that iron bound to liver generates hydroxyl radicals via the Fenton reaction that further damage the DNA.
Collection of large amounts of copper and iron has been reported in the liver and spleen of patients that have caused cancer of the respiratory tract, urinary tract, and thorax. It is thought that enhanced copper content causes DNA damage.  Hydroxyl radicals form the DNA damage marker, and tissue 8-OHdG levels have been shown to be elevated in patients of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. ,
Zinc deficiency leads to dermatitis, alopecia, and taste disorders, and its increased intake causes acute poisoning. In models, development of teratomas and cancers were also documented. Zinc is a component of superoxide dismutase (SOD), an enzyme that removes free radicals, and as it is also needed for DNA activation, repair enzymes, zinc has the antagonist effects and protects against carcinogenesis. ,
In a study where carcinogenesis was seen where animals were exposed to arsenic, and were progressed to the development of precancerous conditions (Bowen's disease) are seen when exposed orally. Chromosomal abnormalities have been seen with the exposure of human leukocytes or cutaneous fibroblasts. 
Association between chromium and carcinogenesis has been found out in relation to lung cancer. A high evidence of lung cancer has been demonstrated as an occupational disease among workers engaged in the chromate production. 
In experiments on rats, induction of rhabdomyosarcoma was reported with an intramuscular injection of nickel sub sulfate, leading to a sarcoma and lung cancer developed. When allowed to inhale nickel dust, and high rates of lung cancer and cancer of the nasal cavity.
Vanadium promotes cell mutation in some cells, causing tyrosine kinase phosphorylation, which possibly exerts an effect on oncogenic activation. As it also interferes with proper chromosome functioning during cell division, the risk of carcinogenicity can't be ruled out.
Lung tumors have been seen in carcinogenesis experiments in response to intra tracheal administration, and intra peritoneal administration, and development of osteosarcoma has been reported with intravenous administration. 
A slight association with the development of lung cancer, stomach cancer, and brain tumors has been documented among workers in a lead smelter, and in lead poisoning. The carcinogenetic mechanism is assumed to be interfering with the DNA repair process.
DNA fragmentation and chromosome abnormalities have been documented in cultured human cells, sarcomas and testicular interstitial cell tumors.
The mechanism of gene mutations by cobalt is known to be DNA breaks and inhibition of DNA repair by cobalt, and gene mutations and carcinogenicity have been reported in cells. 
| Trace Elements in Oral Lesions|| |
Trace metals and oral lichen planus and oral lichenoid reactions 
Lichen planus, contact allergy and hypersensitivity OLR's can be linked to its exposure with metals that are released from metal alloys commonly used in dentistry. There is a hypothesis on a potential link of (OLR's) with exposure to Cr, Co, and Ni and amalgam alloys as released into the oral cavity.  Among them, the most common metal is nickel. These trace metals when come into contact with oral mucosa induce sensitivity reactions in response to the immune-mediated damage of the basal epithelial keratinocytes. Some studies state that OLR due to amalgamation may have a risk of malignant transformation.
Trace elements and oral submucous fibrosis
Oral submucous fibrosis is a well-recognized potentially malignant condition of the oral cavity, leading to oral cancer, a disfiguring and potentially fatal disease. In the developing countries, controlling the devastating, widespread effects of oral cancer needs interventions at-risk persons before the disease becomes invasive, advanced or metastatic. Therefore, early detection of these premalignancies and preventing them from malignant transformation seem to be the best available tool in the fight against oral carcinomas. ,
The function of trace elements in various diseases has been a matter of controversy with various authors. Trace elements have been extensively studied in recent years to assess if they have any modulating effects in the predisposition of oral malignant conditions. Relatively less scientific literature has been documented in the area of oral premalignant conditions, keeping the scientific premises, that the zinc levels in the tissue and serum of pre malignancies may be used in understanding the pathogenesis, and in establishing treatment. 
Trace elements and oral pre cancer and cancer
India has one of the highest incidences of oral cancer in the world. The development of cancer is a multistep process that is seen arising from a pre-existing potentially malignant lesion. Leukoplakia is the most common precancer that is seen representing 85% of such lesions. Alcohol, viruses, genetic mutations, candida infections, and chronic irritation have modifying effects in the etiology of oral cancer. Trace elements are considered as versatile anti-cancer agents that help regulate various biological mechanisms. Many researchers have observed a potential link between the trace elements and cancer mortality. Reduction in the contents of Copper (Cu) and Zinc (Zn) were seen in the blood of patients with head and neck cancer. The ratio of copper to zinc is also believed to be a reliable biomarker in the development and progression toward carcinogenesis. ,,
Trace elements such as copper and zinc have a role in the anticarcinogenic defense mechanism of the human body. Copper is involved in the cell metabolic activity, as a part of various enzymes, which are chiefly concerned with oxidation reactions. In few studies, it was evident that the mean serum copper levels were significantly higher in the sera of patients with oral premalignant and malignant lesions and conditions.  In other literatures, it was seen that there was an elevation of the serum copper in the oral leukoplakia and oral squamous cell carcinoma (OSCC) group. In one recent study, it was seen that the levels of serum copper were raised in OSMF patients and gradually increased as the clinical staging OSMF progressed.
Zinc is a cofactor for Cu-Zn SOD enzyme which is a part of the primary antioxidant system of all groups of vertebrates. Some studies have shown lower zinc levels in the serum of patients with potentially premalignant disorders like in oral leukoplakia. This might be due to the consumption of Zn in counter reacting to oxidants generated from tobacco or high copper of areca quid metabolism.  Though, there was no much significant difference between the serum Zn levels in oral leukoplakia and OSMF groups, researchers also believe that zinc inhibits the invasive/migration potential activities in the malignant prostate cell.
Reduced iron levels in OSMF patients may be due to utility of iron in collagen synthesis. It has been stated that the decreased iron content leads to decreased epithelial vascularity leading to an increased penetration of arecoline, which leading to fibrosis.  Insufficient nutrition due to a burning sensation and erosions in OSMF patients and raised tumor burden in OSCC patients are considered to be key factors for iron depletion.
Future studies investigating the levels of Cu and Zn in precancerous and cancerous tissue and correlating them with serum changes would be useful in establishing the role of these micro-nutrients in oral carcinogenesis. However, it can be stated that Cu and Zn could be effectively used as biological markers in the process of oral carcinogenesis. Serum Cu to Zn ratio could also be used as a reliable biomarker in the literature.
| Conclusion|| |
Though trace elements are required in minimal quantities their presence in the optimal amount is essential for the normal physiological functioning of the body. They are one of the corner stone's in maintenance of biodynamic of the body. Both, excess and the deficiency states lead to initiation, promotion, and progression to various disease processes. The present paper has thoroughly discussed trace elements, as this area is away from the deserved attention. Thus, a comprehensive understanding of these trace elements is essential and significant for disease control and maintaining optimal health.
| References|| |
|1.||Bowen HJ. Trace Elements in Biochemistry. 2 nd ed. New York: Academic Press; 1976. |
|2.||Aliasgharpour M. Trace elements in human nutrition: A review. Int J Med Invest 2013;2:115-28. |
|3.||National Institutes of Health. Office of Dietary Supplements. Available from: http://ods.od.nih.gov/News/ODS_Update.aspx. [Last updated on Winter 2014]. |
|4.||Fifth Congress of the FESTEM (Federation of European Societies on Trace Elements and Minerals). Available from: http://www.festem.eu/. [Last accessed on 2014 May 03]. |
|5.||World Health Organization. Trace elements in human nutrition and health. 1996. ISBN: 92 4 156173 4. |
|6.||Bonda PLF, Porrini R, Rizzio E, Pietra R, Fortaner S, Sabbioni E. Trace elements in the oral mucosa in relation to ruber lichen planus pathology: A preliminary study carried out by neutron activation analysis. J Trace Elem Med Biol 2001;15:79-83. |
|7.||Nayak AG, Chatra L, Shenai PK. Assistant of copper, zinc levels in mucosal tissue and serum of OSMF patients. J Dent 2010;1:75-8. |
|8.||Shetty R, Babu S. Role of trace elements in oral pre cancer and oral cancer - A biochemical study. J Cancer Res Treat 2013;1:1-3. |
|9.||Vyas RK, Gupta AP, Gupta A, Aeron AK. Serum copper, zinc, magnesium and calcium levels in various human diseases. Indian J Med Res 1982;76:301-4. |
|10.||Trace Element Deficiency in Infants and Children. Japan Med Assoc 2004;47:376-81. |
|11.||Nielson FH. Ultratrace elements in nutrition. Annu Rev Nutr 1984;4;21-41. |
|12.||Trace elements. Wikipedia, the free encyclopedia. en.wikipedia.org/wiki/Trace_element. [Last accessed on 2014 May 03]. |
|13.||Nguta JM. Essential trace elements: Trace elements in human and animal health. Germany: LAP, Lambert Academic Publishing; 2010. ISBN-NR: 978-3-8433-7174-2. |
|14.||Rayman MP. Selenium and human health. Lancet 2012;379:1256-68. |
|15.||Coughlan MP. The role of molybdenum in human biology. J Inherit Metab Dis 1983;6 Suppl 1:70-7. |
|16.||Swain N, Ray JG. Altered trace element level and antioxidant activity in whole blood of leukoloplakia and cancer patients in comparison with healthy controls. Int J Oral Maxillofac Pathol 2011;2:2-26. |
|17.||Jayadeep A, Raveendran Pillai K, Kannan S, Nalinakumari KR, Mathew B, Krishnan Nair M, et al. Serum levels of copper, zinc, iron and ceruplasmin in oral leukoplakia and squamous cell carcinoma. J Exp Clin Cancer Res 1997;16:295-300. |
|18.||Fukuda H, Ebara M. Trace elements and cancer. Japan Med Assoc J 2004;47:391-5. |
|19.||Sarode S, Sarode G, Ketki K. Oral lichenoid reactions: A review. Int J Oral Maxillofac Pathol 2012;3:17-26. |
|20.||Tadakamadla J, Kumar S, GP M. Evaluation of serum copper and iron levels among oral submucous fibrosis patients. Med Oral Patol Oral Cir Bucal 2011;16:e870-3. |
|21.||21 Hughes MF, Beck BD, Chen Y, Lewis AS, Thomas DJ. Arsenic exposure and toxicology: A historical perspective. Toxicol Sci 2011;123:305-32. |
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