2071

Received 2020-11-13

Revised 2020-11-20

Accepted 2020-12-05

Role of Zinc in Improvement, Prevention, and Treatment of the Noncommunicable Oral

Diseases: Review of Literature

Farzaneh Agha-Hosseini 1, 2,3, Mahdieh-Sadat Moosavi 1, 2, Sanam Talaei 4

1 Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Oral Medicine, Faculty of Dentistry, Tehran University of Medical Sciences, Tehran, Iran

3 The Academy of Medical Sciences, Tehran, Iran

4 Department of Oral & Maxillofacial Medicine, Alborz University of Medical Sciences, karaj, Iran

Abstract

Zinc, as the second most abundant trace element present in the living organisms after iron, plays a key role in the structural, catalytic, and signaling fields. Beyond the numerous systemic symptoms of zinc deficiency, it may also contribute to different processes of oral diseases.

The articles were collected from three search engines including PUBMED, GOOGLE SCHOLAR, and SCOPUS. The search keywords are as follows: Zinc, trace elements, zinc deficiency, oral diseases, oral lesions, recurrent aphthous stomatitis, oral lichen planus, oral squamous cell carcinoma, burning mouth syndrome, xerostomia, neuropathy. Many diverse articles including original article, case report/case series, and review articles were collected. Several studies have investigated the role of zinc and its deficiency in the development of various types of noncommunicable oral lesions including recurrent aphthous stomatitis (RAS), oral lichen planus (OLP), precancerous lesions of the oral cavity (leukoplakia and submucosal fibrosis), oral cancer, xerostomia and burning mouth syndrome, periodontal disease, and Caries. Therefore, the present research was conducted to review the previous studies performed in this field.

[GMJ.2021;10:e2071] DOI:2071

Keywords: Aphthous Stomatitis; Burning Mouth Syndrome; Oral Cancer; Oral Lichen Planus; Trace Element; Zinc

Correspondence to:

Sanam Talaei, Department of Oral & Maxillofacial Medicine, alborz University of Medical Sciences, katoueizadeh Av, golshahr , karaj, Iran

Telephone Number: +989391872254

Email Address: sanamtalaei66@gmail.com

GMJ.2021;10:e2071

www.gmj.ir

Introduction

Zinc is the second most abundant trace element (transition metal) in living organisms after iron, and is the only metal present in all enzyme classes [1]. Zinc is essential for the life of organisms; this was first approved in 1869 about the species of Aspergillus and subsequently for the growth and evolution of other species, including plants, rats, and birds. In 1961, zinc was discovered as an essential element for humans, and it was reported that its nutritional deficiencies would lead to symptoms such as severe anemia, growth retardation, hypogonadism, skin disorders, and mental lethargy [2].

According to the WHO (World Health Organization) classification in 1973 and the Friedens’ classification in 1981, zinc was included in the essential trace elements. This means that the daily requirement of the body is less than 100 mg. Iron, copper, iodine, and selenium are also in this category [1].

These components enter the body through the diet and, enter the bloodstream in case of deficiency, and they enter the cell in case of low intracellular levels. They are excreted if the blood and intracellular levels are sufficient or increased. The content of zinc required by the body is about 15 mg per day, which is mainly supplied from animal products including meat, milk, and fish. People most at risk for zinc deficiency are vegetarians, the elderly, alcoholics, people with HIV (human immunodeficiency virus), IBD (Inflammatory bowel disease), and the sickle cell anemia. A number of nutritional factors, including cadmium, iron, copper, phytates and fiber may reduce zinc absorption [3].

Numerous studies have described the types of symptoms of zinc deficiency as follows: persistent diarrhea, alopecia, taste disturbances, immune insufficiency, brain dysfunction, wound healing defects, loss of appetite, chronic inflammation, liver disease, and neuropsychological changes such as emotional instability, irritability and depression.

Zinc deficiency is an international concern leading to 4% of child mortality in developing countries. Conversely, zinc deficiency is growing in senior citizens in developed countries.The effectiveness of zinc supplements in humans has been confirmed in the form of reducing mortality from diarrhea in children, improving immune function and reducing the incidence of infections, improving growth and weight gain in children, reducing the incidence of blindness and reducing the risk of age-related macular degeneration.

Zinc has low level of toxicity; it is generally believed to be safe, but its overdose can be toxic resulting in side effects such as inadequate copper absorption [2]. Numerous studies have presented zinc deficiency in various systemic conditions, including psoriasis, acne vulgaris, pernicious anemia, tuberculosis, and liver cirrhosis [4]. Zinc is present as a covalent divalence (Zn2+) and is not redox active (but redox neutral) under biological conditions; it is active in many biological processes as a lewis acid, and therefore it plays a key role in structural, catalytic, and signaling fields. Performing these roles requires specific systems to pass zinc through biological membranes. Therefore, zinc transport proteins play a vital role in the process of physiological effects. In particular, ZnT (Zinc transporter), Zrt (Zinc-regulated transporter), and ZIP (Zrt-like proteins) participate in a variety of cellular and physiological functions, including “immunity, endocrine, reproductive, skeletal, and neurological” through precise control of zinc homeostasis.

Due to its strong Lewis acid property, in catalytic functions, zinc activates substrates in enzymes by steadying negative charges [5].

Zinc also acts as a mediator of signaling processes; hence, it is named “21st Century Calcium”. The signaling function of zinc occurs due to an increase in the concentration of Zn2+, which is triggered by stimuli [2]. Serum zinc contains only 0.1% of the body’s total zinc, 80% of which binds insecurely to albumin, and 20% binds firmly to alpha 2 macroglobulin [6].

0.1% of body zinc is recovered daily by nutrition. Zinc uptake in the duodenum and geogenome is precisely regulated. If dietary intake of zinc is limited, this absorption will increase by up to 90% and if too much zinc is ingested through food, the excess will be released by GI secretions, mucosal cell proliferation, and renal excretion [7, 8]. Therefore, the human body can regulate changes in food intake up to 10 times [2]. Previous studies suggest that use of various spices and herbs in food recipes and medicinal preparations is a source of essential trace metal supplements such as zinc [9].

Search Strategy

Numerous studies have explored the role of zinc and its deficiency in developing various types of oral lesions, including noncommunicable oral diseases such as recurrent aphthous stomatitis (RAS), oral lichen planus (OLP), precancerous lesions of the oral cavity (leukoplakia and submucosal fibrosis), oral cancer, xerostomia and Burning Mouth Syndrome (BMS)F, periodontal disease and Caries. In this study, we decided to review the studies conducted in this field.

The articles were collected from three search engines including PUBMED, GOOGLE SCHOLAR, and SCOPUS. The search keywords are as follows: Zinc, trace elements, zinc deficiency, oral diseases, oral lesions, recurrent aphthous stomatitis, oral lichen planus, oral squamous cell carcinoma (OSCC), burning mouth syndrome, xerostomia, neuropathy. Articles published after 2000 were selected for review.

Results

Many diverse articles including original article, case report/case series, and review articles were collected (PRISMA Flow Diagram). The results of the article review - based on the disorder – have been presented separately in Tables 1 to 5.

Discussion

Given the important and proven role of zinc in structural, catalytic, and signaling processes (known as 21st century calcium because of its basic signaling role), it is important to examine the role of this trace element in the etiopathogenesis of common oral diseases and its therapeutic effect. Based on our review of articles focusing on the effect of zinc on oral disorders, most studies have examined the effect of zinc on oral lesions including RAS, precancerous and malignant lesions, OLP, periodontal disease, xerostomia, BMS, and taste disorders.

RAS

The etiology of RAS is unknown, but an autoimmune theory has been proposed for it due to the presence of antibodies against epithelial antigens. The potential role of zinc as a modifier of the RAS course may be due to the ability of zinc to stimulate the production of IL1, IL6, TNFα in peripheral blood mononuclear cells and monocytes and because of its deficiency, IL2 secretion may be restricted resulting in a decrease in the number of T-helper1 (Th1) cells and cytokines (showing the importance of Th1-induced immunity in RAS etiopathogenesis).

The following reasons have led to the study of zinc in these patients:

1) Zinc participation in the ongoing wound healing process

2) Being the scavenger of free radicals due to its antioxidant activity

According to Table-1, studies on the relationship between zinc and RAS can be divided into three categories:

1) The first category includes the studies examining the serum in patients with RAS. As shown in Table-1, there are conflicting results in this regard. Some studies reported a significant deficiency in patients and others did not achieve any significant results.

2) The second category includes the studies that have examined the results of the effect of systemic treatment on patients with RAS. In this regard, the results have been also contradictory; some studies reported this type of treatment to be significantly effective, while others did not achieve significant results.

3) The third category of studies measured the local effect of zinc on RAS. Only one study was performed in this regard, according to which, topical treatment did not lead to a significant difference in the wound healing process [10].

Finally, the assessment on Behcet’s syndrome, which has been conducted by measuring the serum levels of various vitamins and trace elements, including vitamins A, C, E, and β-carotene, selenium, and zinc, revealed that zinc levels in these individuals were even higher than in healthy individuals [11].

Pre-malignant / Malignant Oral Lesions

In studies conducted with the aim of investigating the role of zinc in pre-malignant and malignant oral lesions, the largest volume of studies has been on Oral Sub Mucous Fibrosis (OSMF), which includes a series of repeated studies (Table-2). In 11 studies performed on serum, all but one study reported significantly lower levels of zinc in the serum of patients with OSMF. While in salivary studies (3 studies in total), a significant decrease in zinc in saliva of patients with OSMF was reported in only one study and no significant differences were reported in the other two studies; the only study on zinc mucosal levels in OSMF reported significant reduced levels.

* The results of 12 studies on the effects of zinc on oral cancer have been found to be contradictory. The results of 9 studies on serum are also contradictory; 6 studies reported a significant decrease, 1 study a non-significant increase and 1 study a significant increase in zinc in the serum of patients with oral cancer. One study also claimed that the relationship between serum zinc and oral cancer was U-shaped and its overuse and deficiency both leads to an increased risk of oral cancer.

Seven studies have been performed on the effect of zinc on leukoplakia. Out of six studies performed on serum, all but one study reported a significant reduction in serum zinc in patients. In addition, in the only study performed on saliva in this group, a significant reduction in zinc levels was reported. According to the hypotheses of these studies, superoxide dismutase, a natural antioxidant in the body, is a protein complex containing Zinc-Copper. It has been proven - in OSMF - to have anti-carcinogenic effect. Zn inhibits the cross-linking of collagen peptides by reducing the activity of lysyl oxidase enzyme containing copper. In addition, through collagenase and matrix metalloproteinases, it leads to partial breakdown of collagen. Therefore, zinc and copper are inversely related and excess zinc interferes with the mucosal absorption of copper (because both elements are absorbed through metallothioneins).

Zinc is a cofactor for the enzyme superoxide dismutase, and several studies have shown that serum zinc is reduced in precancerous lesions such as leukoplakia. Low serum zinc levels in patients with OSCC and OSMF are probably because malignant cells need higher content of zinc, and the removal of these excess amounts from serum leads to a decrease in serum zinc [12].

Zinc may stop carcinogenesis through two mechanisms by playing its antioxidant role:

1. Protecting sulfhydryl groups against oxidation and hindering production of reactive oxygen species by transition metals.

2. Concentrations above the physiological limit of zinc have an antioxidant-like effect (In organelle-based systems and isolated cell-based systems).

Therefore, a decrease in zinc and zinc-dependent superoxide dismutase levels may indicate early mucosal changes prior to carcinogenesis [13,14] and probably zinc supplementation treatment would reduce the risk of developing precancerous lesions, and zinc would play a protective role in the progression of precancerous lesions [15].

Zinc deficiency disrupts apoptosis and DNA repair processes, leading to increased cell susceptibility to oxidative stress; it also induces overexpression of Cyclooxygenase-2 (COX2), stimulates cell proliferation, and inhibits apoptosis. Thus, zinc deficiency plays a role in the progression of precancerous diseases to oral cancer [16].

In addition, zinc deficiency may contribute to the onset of cancer by activating nuclear factor kappa B (Nf k-β) expression and subsequently inducing tumorigenesis signaling [17, 18].

Contrary to popular belief that zinc always has a protective function, limited articles suggest carcinogenic effects for high zinc cases [1, 19].

The toxic effects of zinc, even at micromolar levels, have been demonstrated under H2O2-induced oxidative stress. Zinc appears to be involved in acute cell death induced by H2O2 [20].

Therefore, despite the protective role of zinc against oxidative stress, what is important is that if its intracellular levels increase, it will have toxic effects on the cell. Since high levels of zinc can stimulate telomerase activity, leading to indefinite proliferation of tumor cells, excess amounts of free zinc ions can lead to oxidative damage in mitochondria [21].

OLP

Studies examining zinc and OLP are limited. Serum levels have been examined in three studies and, the effect of systemic therapy in one study and the effect of topical administration in one study (Table-3) show that, because insufficient studies, it cannot be discussed comprehensively. The reasons given for these studies are:

Zinc activates caspase-3 and DNA fragmentation, leading to keratinocyte apoptosis and inhibition of matrix metalloproteinase (MMP)1 activation and as a result, it prevents the accumulation of Tcell in OLP.

It also inhibits collagen IV cleavage by inhibiting MMP9 and maintains the integrity of the basement membrane [22, 23].

Treatment with zinc supplementation does not allow the reactive oxygen species (ROS) to be produced adequately and it decreased the expression of COX2 and finally the release of prostaglandin E2 (PGE2); thus zinc treatment reduces oral inflammation [24]. In OLP, an autoimmune reaction occurs by Tcell CD8+ [25], which results in the release of several cytokines, including tumor necrosis factor (TNF)α and interleukin (IL)12. These cytokines lead to a loss of mucosal membrane integrity [26].

Following OLP treatment with systemic zinc, a significant reduction in the burning sensation, pain and size of the lesions has been observed, which can be justified by its anti-inflammatory properties and the ability to heal wound [22].

Taste Disorders, Xerostomia and BMS

Zinc influences the sense of taste by affecting various targets including saliva, taste buds, sensory-neurotransmission, and brain. In the taste receptor, zinc not only affects the direct binding of tastants to the bud receptor, but also the transduction of this chemical energy.

Zinc has a key role in maintaining the integrity of cell membranes, cell structure, and the performance of various enzymes; zinc deficiency can lead to taste disorder, for any reason. Reciprocally, in any patient with a complaint of dysgeusia, it is necessary to measure and correct zinc levels.

Histochemical studies have shown that the enzyme alkaline phosphatase, a zinc-dependent enzyme, is present in taste buds.

Lower levels of normal zinc were found in the saliva of some people with hypogeusia. One of the salivary metalloproteins carrying zinc is called gustin, which plays a role in the development and nutrition of taste buds.

Gustin levels in patients with hypogeusia were lower than normal level. This caused pathological variations in the taste buds and dysgeusia. Gustin was increased with zinc therapy and the taste problem was resolved [27].

In rats, zinc deficiency has led to a reduction in salivary gland weight and decreased secretory activity. It also reduced the activity of alkaline phosphatase enzyme to 44% N and carbonic anhydrase to 26% N. In addition, zinc deficiency leads to a decrease in the activity of calmodulin, a calcium-binding protein, and ultimately to a decrease in Ca2+ _ATPase activity. Thus, contracting of the sarcoepithelial cells become defective, reducing salivary gland secretory function [27].

Limited studies in this category (Table-4) have shown that serum zinc is lower in patients with Burning Mouth Syndrome, xerostomia, and taste disorders compared to healthy individuals, and zinc deficiency is more common in these people. However, no significant difference was observed in a study conducted on the saliva of people with BMS.

In all studies examining BMS, it is important to determine whether the case group includes patients with primary or secondary BMS, because primary and secondary BMS are different clinically and paraclinically and in terms of etiopathogenesis and management.

Therefore, to rule out secondary BMS, a comprehensive test is needed to measure the factors contributing to oral burning sensation (including serum iron levels, vitamin B12, fasting blood sugar (FBS); besides, it is essential to perform a thorough oral examination to rule out conditions such as candidiasis, lichen planus, parafunctional habits, and related underlying diseases such as diabetes, in these patients.

Periodontal Disease/caries

Studies on the effect of zinc on caries and periodontal disease (Table-5) are very limited that are often done on animals and cannot be cited for a comprehensive discussion and conclusion. The issues discussed in these limited studies are:

In a study on rats, zinc deficiency led to parakeratosis in the mucosa, which is naturally orthokeratinized [1].

Therefore, it can be suggested that zinc is a potential risk factor for oral and periodontal diseases. [28] Common manifestations of zinc deficiency in these studies include thickening of the buccal mucosa and loss of filiform papillae of tongue [1].

The presence of zinc in addition to fluoride and calcium in the mouthwash composition leads to inhibition of tooth demineralization and it enhances its remineralization, and can be useful in preventing root caries. Zinc is added to oral health products due to its properties such as reducing the formation of calculus, controlling plaque, and reducing halitosis, and it has the ability to stay in saliva and plaque for hours [19].

It is important that positive results do not lead to misconceptions about the need for oral hygiene - as the most important factor - to prevent caries and periodontal diseases, and it is necessary to emphasize this issue in studies.

The intracellular distribution of zinc is 50% in plasma, 30-40% in nucleus and 10% in membrane. These ratios fluctuate in response to different stimuli and these temporary fluctuations play a key role in the zinc signaling process [2].

Despite the fact that the amount of serum/plasma zinc is a general indicator for the whole body zinc, but this amount does not necessarily reflect the zinc content in different tissues and, this can be considered as the reason for the effectiveness and success of zinc supplement therapy in some patients with normal serum zinc range.

Therefore, it is better to use methods for local measurement of zinc in the target tissue (oral mucosa). The Erythrocytic 65 Zn uptake test, which is a plasma indicator for determining the nutritional status of zinc, may have diagnostic value, but it is not commonly used [3, 29].

Many trace elements interfere with the process of absorption, metabolism, and homeostasis of zinc. From this category, we can mention “iron”. In blood plasma, zinc is bound to albumin (60%) and transferrin (40%) and is transported through it. Since transferrin also carries iron, excess iron reduces the zinc uptake, and conversely, higher levels of zinc in serum are expected in people with iron deficiency anemia [1, 30].

In addition, since zinc and “copper” (Cu) are both absorbed through metallothioneins, they are inversely related, and excess zinc interferes with the mucosal absorption of copper.

For example, in addition to zinc, Ozturk et al. also measured selenium and copper in patients with RAS and reported lower levels of selenium, higher copper, higher Cu/Zn, and higher Cu/Se ratios for people with RAS compared to healthy people.

They stated that the Cu/Zn and Cu/Se ratios could be used as biochemical markers for RAS; disruption of the Cu/Zn ratio will lead to a decrease in the antioxidant capacity of the blood and an increase in inflammatory responses and these processes are in favor of RAS [31].

However, if B12, transferrin, and iron were also measured, the results might still change.

Conclusion

Considering these interactions and the co-factorial and complex involvement of zinc in many mechanisms, it is suggested that for evaluating the role of zinc in the etiopathogenesis of oral diseases or its therapeutic and preventive effect, besides zinc, albumin, Cu/Zn ratio, iron, copper, folic acid, selenium, transferrin, vitamin B12 and alkaline phosphatase should also be measured.

In addition, in terms of treatment, its amount should be measured before and after the intervention so that a more comprehensive insight can be achieved in terms of its effectiveness and mechanism.

Conflict of Interest

None.

Table 1. Studies on serum status and the effect of various zinc treatments on RAS

Conclusion

Total number of subjects

Study type

Objective

Author

No significant difference between RAS and control groups

99

Case– control

Evaluation of serum levels in cutaneous disorders

Arora et al.

2002 [32]

Reduced recurrence criteria

40

Case –control

Evaluation of the effect of systemic treatment

Orbak et al.

2003 [33]

significantly lower levels in the case group

88

Case –control

Comparative study of serum levels with healthy individuals

Khademi , Shaikhiany

2006 [34]

more significant effect than Dapson

45

RCT

(Double-blind placebo controlled study)

Evaluation of therapeutic and preventive effect of systemic administration (compared to Dapsone)

Sharquie et al.

2008 [35]

significantly higher Cu / Zn ratio in patients and significantly lower serum levels in patients

63

Case – control

Investigation of serum levels and Cu / Zn ratio

Ozturk et al.

2013 [31]

Significantly lower in the case group

50

Case – control

Comparative study of serum levels with healthy individuals

Ozler

2014 [36]

Lack of superiority of this treatment

20

RCT

Double-blind clinical trial

Evaluation of the therapeutic effect of mouthwash

Mehdipour et al.

2016 [10]

Significantly lower in patients

483

Case – control

Examination of the serum levels

Bao ZX

2016 [37]

no significant difference in serum levels and no effect on the course of the disease

147

Case – control

Comparative study of serum levels with healthy individuals

Slebioda et al.

2017 [4]

Table 2. Studies on the status and effect of zinc on malignant and precancerous lesions of the mouth.

Conclusion

N

Study type

objectives

Authors

Playing a protective role

970

CC

Evaluation of the effect of supplementation on precancerous lesions of the mouth

Hebert et al.

2001 [15]

Significant decrease

60

CC

Evaluation of serum levels in OSMF

Shettar et al. 2010 [38]

No significant difference

Significant decrease

Significant decrease

150

CC

Evaluation of serum levels in

Leukoplakia OSMF OSCC

Balpande et al. 2010 [12]

Significant reduction in both

150

CC

Assessment of serum levels in leukoplakia and OSCC

Swain et al.

2011 [39]

Significant reduction in both

150

CC

Assessment of serum levels in leukoplakia and OSMF

Ray et al.

2011 [40]

No significant difference

70

CC

Investigation of salivary levels in OSMF

Chitra et al.

2012 [41]

Significant reduction

(And a significant reduction with disease progression)

60

CC

Evaluation of serum levels in OSMF

Neethi et al.

2013 [42]

Slight and insignificant increase in both

90

CC

Assessment of serum levels in OSMF, OSCC

Khanna et al.

2013 [43]

Significant decrease

100

CC

Evaluation of serum levels in OSMF

Kapoor et al.

2013 [44]

Significant reduction in all three and significant differences between different OSCC grades

150

CC

Evaluation of serum levels in leukoplakia, OSMF and OSCC

Singh et al.

2015 [45]

Significant reduction in all three

200

CC

Evaluation of salivary levels in leukoplakia, OSMF and OSCC

Shetty et al.

2015 [13]

Significant increase

30

CC

Evaluation of serum levels in oral cancer

Keerthika et al.

2016 [46]

No significant difference

60

CC

Investigation of salivary levels in OSMF

Dey et al.

2016 [47]

Significant decrease in both

90

CC

Examination of serum levels in OSMF and OSCC

Yunus et al.

2017 [48]

Significant decrease

60

CC

Examination of mucosal levels in OSMF

Singh J ,

Singh S

2018 [49]

Significant decrease

34

RAm

Evaluation of serum levels in OSMF

Sachdev et al. 2018 [16]

Positive U-shaped curve

1466

CC

Investigation of the relationship between serum levels and the risk of oral cancer

Chen et al.

2019 [50]

Significant reduction in both

80

CC

Evaluation of serum levels in Leukoplakia and OSMF

Garg et al.

2020 [51]

a reliable diagnostic role in the form of Cu / Zn ratio

N/A

RA

Investigation of its role as a biomarker in malignant and precancerous lesions

Rathod et al.

2020 [17]

N: Total number of subjects, CC: Case - control, RAm: Review article (meta-analysis), RA: Review article

Table 3. Studies on the status and effect of zinc in OLP

Conclusion

Total number of subjects

Study type

objectives

Authors

0.2 % zinc containing mouthwash+fluocinolone ointment

Significant reduction of surface area of lesions

20

Case - control

Examination of the effect of topical prescription on EOLP (erosive oral lichen planus)

Mehdipour M et al.

2010 [52]

Order of significant reduction of serum levels:

EOLP<OLP<NORMAL

88

Case - control

Comparative study of serum levels in EOLP, OLP and healthy individuals

Gholizadeh N. et al.

2014 [53]

Significantly lower in patients

483

Case - control

Evaluation of serum levels in OLP

Bao ZX. et al.

2016 [37]

Significant reduction in burning sensation (VAS) and lesion size (Global Index Score)

3

Case report

(case series)

Evaluation of the effect of systemic administration on the improvement of symptomatic OLP

Chaitanya et al.

2019 [22]

Significant increase in the Cu / Zn ratio and a significant decrease in serum levels in patients

80

Cross sectional study

Case - control

Comparative study of serum levels OLP versus control

Garg et al.

2020 [51]

Table 4. Studies on the status and effect of zinc on BMS, xerostomia, and taste disorders

Conclusion

Total number of subjects

Study type

objectives

Authors

Recovery after 6 months of zinc therapy

lower flow rate in its absence

150

Case - Control

Evaluation of the relationship between salivary gland function in patients with taste disorders or xerostomia with its deficiency

Tanaka.M

2002 [27]

No significant difference

60

Case - Control

Investigation of salivary levels in BMS

Pekiner et al.

2009 [54]

74% of people with BMS have zinc deficiency

Significant reduction in numerical pain standard (NS)

55

Case - Control

Investigating the cause and effect relationship between Zinc deficiency and BMS

The effect of systemic administration on BMS

Cho et al.

2010 [55]

Significantly lower in patients

483

Case - Control

Evaluation of serum levels in BMS and xerostomia

Bao ZX. et al.

2016 [37]

Table 5. Studies on the status and effect of zinc on caries and periodontal diseases

Conclusion

Total number of subjects

Study type

objectives

Authors

Significant reduction of gingival index and plaque index

14

Case – control

Animal study

Evaluation of the effect of its systemic administration on periodontal diseases

Orbak et al.

2007 [56]

1 Significantly higher levels

2 Lower levels but not significant

3 Significantly higher levels

600

Case – control

Comparative study (with healthy control group) of serum levels in

1 Type II diabetics without periodontitis

2 Type II diabetics with periodontitis

3 Non-diabetics with periodontitis

Pushparani et al.

2014 [21]

Significant reduction of gingival index

14

Case – control

Animal study

Evaluation of the effect of its systemic administration on periodontal diseases

Seyedmajidi et al.

2014 [57]

Inhibition of bacterial biofilm formation, and root dentin demineralization

30 extracted teeth

Animal study

Case – control

Inhibitory effect of desensitizing compounds

Saad et al.

2019 [58]

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