Oral cavity is the window of zinc and copper deficiency


    Diet and vitamins have an effect on oral health in lots of methods which have an impact on craniofacial improvement and increase and upkeep of dental and oral smooth tissues. 

    Teeth and bones appear as the maximum mineralized tissues in humans. 

    Several reviews advise affiliation among enamel loss or small range of closing enamel and decreased bone mineral density (BMD).

    Appropriate nutrition of all of the metabolically lively cells and tissues is important for keeping fitness of the human body as a whole. 

    Micronutrients, which include hint elements, vitamins, and antioxidants, play a critical function in constantly taking place regenerative processes, handling ongoing oxidative strain in the body tissues, and maintaining enough immunity in opposition to pathogens. 

    The manifestations of undernutrition as nicely overnutrition of micronutrients at the oral health are vast and might bring about defects of the dental hard tissues in addition to oral mucosa.



    Dietary sources of zinc are Meat,wheat,quinoa,rice,Eggs,oats,pine nuts,milk,peanuts,cashews,cheese,almonds,legumes

    Normal serum level of Zn is 84-159 µg/dl. Recommended daily intake (RDI) of zinc is about 11 mg for an adult male and 8 mg for an adult female

    Zinc, a vital chemical element for the expansion of humans and other animals, features a distinctive and intensive role in biological processes. 

    Zinc is stored in 

    • Prostate
    • Parts of the eye
    • Brain
    • Muscle
    • Bones
    • Kidney
    • Liver.  

    Zinc plays an important role in 

    • Immune function
    • Wound healing
    • Protein synthesis
    • Deoxyribonucleic acid synthesis
    • Cell division
    • For the correct sense of taste and smell
    • Supports normal growth and development throughout pregnancy, childhood, and adolescence. 

    Allegedly, it also possesses inhibitor properties and so might play a job in rushing up the healing method once an injury and protective against accelerated aging .  

    A outstanding feature of zn deficiency is that the broad vary of created pathologies and a spectrum of clinical manifestations such as 

    • Impaired growth
    • Alopecia
    • Anemia
    • Dwarfism
    • Impaired sexual development
    • Dermatitis
    • Poor appetite
    • Abnormal dark adaptation
    • Delayed wound healing and 
    • Mental lethargy. 

    Zinc is one in all the foremost potent inhibitors of amino alkanoic acid proteases, including kallikrein. 

    Zinc is additionally contained in alkaline enzymes and plays a very important role within the activation of this enzyme. 

    The bulk of zinc could be accumulated in teeth directly once their eruption, and supermolecule binding is a mechanism that determines the zinc level.

    Zinc rich foods



    Dietary sources of zinc are seafood, chickpeas, potatoes, dark leafy greens, salmon, dark chocolate, sesame seeds, cashews, mushrooms, tofu, avocados, whole grains, beans, nuts, dried fruits

    Normal serum level of Zn is 85-180 µg/dl. Recommended daily intake (RDI) of copper is about 1,400 µg for an adult male and 1,100 µg for an adult female

    Copper is the third most abundant chemical element with solely 75–100 mg of total quantity within the human body. 

    Copper is present in nearly each tissue of the body and is kept principally in the liver together with the brain, heart, kidney, and muscles. 

    Ceruloplasmin, a serious copper carrying macromolecule in the blood, oxidizes metallic element iron to ferric kind that permits iron to be transported in the circulation and bind to transferrin.  

    Copper plays an important role in 

    • Vital role within the structure and performance of the central nervous system. 
    • Assembly of the internal secretion thyroxine. 
    • Production of hemoglobin. 
    • Tyrosinase (Copper containing enzyme) converts amino alkanoic acid to melanin. 
    • Synthesis of phospholipids found in myelin sheaths in peripheral nerves. 
    • Lysyl enzyme that takes half in the synthesis of scleroprotein and elastinn
    • Enzyme (cytochrome oxidase, comprising copper and iron) plays a significant role in energy production throughout aerobic respiration.

    Copper deficiency will occur in prolonged total parenteral nutrition with inadequate copper supplementation, with hematologic abnormalities responding promptly to copper replacement. 

    Copper deficiency cause 

    • Anemia (microcytic, normocytic, or macrocytic)
    • Neutropenia
    • Infections
    • Drug toxicity
    • Myelopathy
    • Peripheral neuropathy 
    • Autoimmunity
    • B12 deficiency
    • Folic acid deficiency
    • Myelodysplastic syndrome
    • Aplastic anemia
    • Lymphoma with bone marrow involvement

    Microscopic slide smear of red blood cells showed abnormal deposition of iron in the mitochondria which forms a ring around the nucleus which commonly occur in myelodysplastic syndrome and copper deficiency.

    Photo credit: Paulo Henrique Orlandi Mourao (wikipedia commons)


    Zinc and copper exert antagonistic effects through the competitive mechanism involving competition for absorption between these bioelements. 

    Predominant concentration of 1 of them leads to the displacement of the second one, inflicting its deficiency within the body. 

    Taking zinc doses that are abundant beyond a daily reference value over long periods might cause copper absorption disorders. 

    In addition, several other effects, that were at first attributed to excess copper in the body, are caused by copper deficiency induced by high doses of this metal. 

    On the opposite hand, copper deficiency will increase zinc toxicity. 

    This relationship might apply to tooth enamel that is created within the process of amelogenesis.


    Systemic BMD is also a risk issue for the event of tooth loss and oral health issues even though enamel doesn't have the standard structure of human bone, its chemical composition is similar. 

    Hydroxyapatite and Mg phosphate are building minerals essential for bone structure, quality, and resistance whereas some trace parts (i.e., zinc and copper) are vital for bone integrity and elasticity. 

    Enamel is ceaselessly laid low with the method of damage. 

    Although tooth wear is recognized as a physiological and irreversible phenomenon, there are people in whom this process of wear happens dramatically quicker and, if not treated, could lead to the whole destruction of the stomatognathic system.   

    Excessive enamel erosion amid uncommon abrasive processes, each being core problems in tooth wear, couldn't be directly compared with porosity or fibrous tissue thinning in bone, that seem essential in osteoporosis.

    Zinc conjointly interacts with hydroxyapatite through the absorption to the crystal surface and its incorporation within the crystal lattice. 

    Low concentrations of this element modify or inhibit remineralization; however, they also considerably cut back enamel dissolution. 

    Zinc has been reported to cut back enamel solubility.
    Zinc is incorporated into enamel throughout remineralization in place despite a moderate level of a rise in zinc concentration.
    Zinc could be a constituent of roughly 300 enzymes, as well as those essential for bone metabolism (bone alkalic phosphate).
    Copper incorporates a direct protecting impact on the dissolution of enamel in acidic environment, being a significant drive for each tooth decay and erosion.
    Inhibition of enamel remineralization by Cu, presumptively due to ionic interaction with the active enamel surface following demineralization.
    Copper is aconcerned in bone metabolism as a cofactor of lysyl oxidase, one in every of the principal enzymes taking part in scleroprotein cross-linking.

    Photo credits: KDS4444 (wikipedia commons)


    In the oral cavity, zinc is of course present in numerous sites such as saliva, dental plaque and dental hard tissues. 

    Supplementation with zinc is effective against totally different oral diseases, for example, gingivitis, periodontitis, halitosis, and differentials, whereas zinc deficiency has been related to poor oral and periodontal health. 

    Zinc plays a crucial role in cell structure architecture, maintaining the cytomembrane integrity, and functions of assorted cytoplasmic and membrane enzymes.

    Zn plays a major role in promoting albuminoid degradation through enzyme and matrix metalloproteinase. 

    Zinc notably impairs copper absorption as both metals are absorbed through metallothioneins. 

    Zinc deficiency was found to be associated with the pathological process of other common oral membrane diseases such as oral lichen planus, burning mouth syndrome, atrophic glossitis, and xerostomia. 


    zinc is more targeted within the superficial layer of the enamel, creating it tougher than the subsurface and more resistant to dental caries.

    Toothpaste containing each fluoride and zinc has been evidenced to be simpler in preventing dentine demineralization and promoting remineralization, in comparison to those containing fluoride alone. 

    An increased concentration of zinc was also found to inhibit bacterial growth by targeting glycolytic enzymes particularly in streptococci mutants, inhibit acid production in plaque and inhibit the formation of plaque, all of that contribute to tooth decay prevalence.  

    Zinc is transformed into an oral health product to regulate plaque, scale back malodor, and retard calculus formation. The zinc elevated concentrations can be sustained for prolonged periods in plaque and saliva following delivery from mouthrinses and toothpastes. 


    Zinc supplementation is effective in preventing gingival disease; it will fight against Fusobacterium nucleatum and Prevotella intermedia, that cause gingivitis. 

    zinc also inhibits proteases made by Porphyromonas gingivalis. 

    zinc oxide nanoparticles were found to disrupt the cell membrane and oxidative stress in Campylobacter species further as in different gram-positive and gram-negative microorganisms found in gingivitis. 


    zinc, further as different trace elements, might function as a helpful biomarker of oral squamous cell cancer and progression from premalignant to malignant oral lesions. 

    Primarily, it's so vital to examine zinc levels in patients with suspicious lesions for early detection and treatment initiation for oral epithelial cell carcinoma that may lead to better prognosis 

    The quantitative relation of copper to zinc is additionally believed to be a reliable biomarker within the development and progression towards carcinogenesis 

    Zinc is a compound for superoxide dismutase enzyme and various studies have shown lower levels of serum zinc in patients with doubtless premalignant disorders like oral leukoplakia. 

    Although low concentrations of zinc will each scale back enamel demineralisation and modify remineralisation, the anticariogenic effectivity is yet disputable and not supported by varied researches. 


    Oral mucositis could be an acute inflammation of the oral membrane following exposure to either therapy and/or radiotherapy. 

    It harms the quality of life as patients have problems eating, drinking, and swallowing because of mouth pain. 

    zinc is a promising strategy for delaying the occurrence of chemotherapy-induced oral mucositis and reducing its intensity. 

    Zn level is considerably lower in perennial Aphthous stomatitis (RAS) patients, thus the determination of blood serum Zinc level, and prescribing metal if its humour level is low, are suggested in RAS patients. 

    Superoxide dismutase that could be a natural antioxidant of the body is a Cu-Zn macromolecule complex that has an anticarcinogenic impact in Oral submucous fibrosis. 


    Zinc deficiency has been associated with remittent style and lingual nervus trigeminus sensitivities further as reduced secretion flow. 

    The role of zinc in taste functions is considerable at various levels of organization resembling taste buds, the taste sense, nerve transmission, and brain.

    Early researchers ended that zinc deficiency secondary to any etiology results in taste disturbances and therefore still zinc depletion is corrected for patients coverage with taste imbalances. 

    The parakeratotic changes in cheek, tongue, and passageway are a proof of zinc deficiency. 

    Thickening of the buccal membrane could be a common manifestation together with loss of filiform papillae. In the oral cavity, zinc is present naturally in plaque, spittle, and enamel. 


    Low dietary intake of copper or its deficiency on bone matrix throughout growth, manufacturing reduced bone strength and, thereby, the clinically apparent osteoporosis. 

    Numerous studies found that the mean serum copper levels were considerably higher within the sera of patients with oral probably malignant disorders equivalent to oral leukoplakia and oral submucous fibrosis and conjointly malignant tumors such as epithelial cell carcinoma.  

    It's been postulated that copper discharged from areca nuts whereas chew came in direct contact with the oral epithelium and is dissolved in the spittle. 

    Copper is reportedly present in the saliva for as long as 30 minutes. 

    The longer the presence of copper in saliva, the higher the chances of its uptake by the oral epithelium. 

    It's been advocated that copper seems within the blood once 15 mins of intake of betel nut and its products. 

    In oral submucous fibrosis patients, the serum levels of copper gradually increase because the clinical stage of the illness progresses. 

    However, native results of raised salivary copper could have a lot of more important roles to play than the raised serum levels. 

    Alternative schools of thoughts appraised decrease in the copper serum concentrations because of usage of copper in upregulation of lysyl enzyme resulting in excessive cross linkage of collagen. 

    Deficiency of cu in diet for a prolonged amount particularly during stages of active growth ends up in anemia and defective organic process within the rima oris. 

    The anemic result is attributed to reduced ferroxidase activity of ceruloplasmin and reduced iron oxidation. 

    Bone changes in copper deficiency embody a loss of trabecular formation with dilution of the cortex. 

    There could also be pathology and occipital horn formation because of useful impairment of copper-requiring enzymes equivalent to ascorbate oxidase and lysyl oxidase just in case of copper deficiency.  

    Lowered immunity may end up in numerous infections of the oral cavity due to attended neutropenia. 

    Granulocyte maturation disorder within the bone marrow and condition in neutrophils are noted.

    Absorption and distribution of copper 


    Oral submucous fibrosis (OSF) could be a probably malignant disorder that causes fibrosis and inflammation of the oral mucosa. 

    Chewing of areca nut is the primary etiological issue for the event of OSF. 

    Inflammatory response to areca nut chewing, followed by fibrosis of the oral submucosa and so progresses to induce restriction of the mouth opening and problem in chewing and swallowing. 

    Chewing of areca nut generates reactive element species, which might cause injury to the proteins and nucleic acids within the body. 

    Zn induces activation of antioxidant catalyst superoxide dismutase (SOD) which inhibits production of reactive oxygen species. 

    Areca nut contain a high content of copper that's discharged among 5–30 minutes of chewing the nut, inducement upregulation of lysyl enzyme within the oral mucosa. 


    Dietary Zn interferes with Cu absorption by inducing the synthesis of metallothionein, a protein that sequesters copper, creating it unavailable for absorption. 

    Neutralization of free radicals generated by the betel nut might cause excessive cellular uptake of Zn, thereby leading to diminished Zn levels in the patients. 

    Zn additionally may play a very important role in preventing the event of malignancy. 

    The Zn-dependent protein p-53 gene is concerned in the repair of DNA. 

    In addition, the transcription factors of AP-1 and NF-kB that regulate programmed cell death and defense responses against aerophilic stress will bear alterations with the reduction in cellular levels of metallic elements. 

    Thus, deficiency of zinc may disrupt the processes of deoxyribonucleic acid repair, apoptosis, and increase the status of the cells to oxidative stress. 

    A lack of Zn additionally induces overexpression of cyclooxygenase-2 which can promote cell proliferation and inhibit apoptosis, thereby contributing to the malignant transformation of OSF to oral carcinomas. 


    Cu/Zn-superoxide dismutase catalyst (Cu/Zn-SOD) to function as the first-line of defense against reactive element species within the cells. 

    Cu is present in high concentrations, it generates reactive oxygen species that induce aerophilic injury to the cell. 

    High levels of cu in the blood serum of OSF patients additionally could also be attributed to the inflammatory response to the betel nut, within which the liver releases the copper-carrying ceruloplasmin protein. 

    OSF induces a state of oxidative stress, wherever ceruloplasmin may be releasing raised copper in the body. 

    The mastication of the areca nut releases copper which is taken into the oral tissue layer keratinocytes through a non-enzyme-dependent diffusion process, sure to the protein metallothionein. 

    High intracellular levels of copper will generate hydroxyl group radicals that cause damage to the DNA and protein molecules. 

    In addition, this could activate angiogenesis factors resembling tumour necrosis factor alpha and vascular epithelial tissue growth factor. 

    These angiogenic factors play a very important role in tumor growth and metastasis. 

    The blood level of ceruloplasmin (a Cu-transporting protein) has been discovered to be raised from four- to eightfold throughout OSF malignancy. 

    Ceruloplasmin is a supply of Cu(I) ions, which can initiate the method of low-density lipoprotein oxidation and play a job within the malignant transformation of OSF to oral carcinoma. 

    The high copper content can generate reactive oxygen species by Fenton and Haber–Weiss reaction.

    Photo credit: Bakshi SS. Oral submucous fibrosis. J Otolaryngol ENT Res. 2018;10(3):137. DOI: 10.15406/joentr.2018.10.00330


    Oral and general health can't be viewed severally and as a matter of truth the oral cavity will mirror the general health effectively. 

    The mixture of varied micronutrients and trace components has been used as a treatment strategy for oral diseases like oral leukoplakia, oral submucous fibrosis, oral cancer, and then forth as their collective outcome is additional useful as compared to solitary application. 

    zinc and copper supplements ought to incline to speculative teams such as pregnant women, children, adolescents and the elderly, particularly in developing countries. 

    Hence, information of the clinical aspects of trace components (micronutrients) is turning into requisite for general as well as dentists. 


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