Fluoride and Other Trace Elements in Dental Hard Tissue

Abstract

Fluorides and other trace elements are a part of various biological and chemical responses in the human body. They collaboratively work with all proteins, enzymes, and co-enzymes to carry out the different functions and in redox reactions. The dietary substances may not have an adequate amount of these essential trace elements, resulting in the development of dental soft and hard tissue disorders associated with their deficiencies. To tackle this, dietary supplements will be needed. So, the current chapter has thoroughly addressed the importance of trace elements in dental hard tissues. This has also discussed the effect of fluoride and other trace elements on dental hard tissues, as there is limited literature available in this area. This will provide an overall understanding of how trace elements are an essential part and their importance in oral diseases control and prevention.

1. Introduction

Carbon, hydrogen, and nitrogen elements make up about 96 percent of all living things. In the living system, nearly half of all recognized elements are present in detectable concentrations. The physiological activities of 23 elements are identified in humans and other mammals, 11 of which are categorized as trace elements (TEs) [1]. Vanadium, chromium, manganese (Mn), iron (Fe), cobalt, copper (Cu), zinc (Zn), and molybdenum are transition elements, while selenium (Se), fluorine, and iodine are non-metal elements [1, 2]. TEs, unlike sodium, calcium, magnesium, potassium, and chlorine, which are macronutrients that must be consumed in large quantities, are micronutrients that must be consumed in small amounts. (usually lower than 100 mg/day). Major and Minor TEs are both essential for human health. Due to natural or man-made causes, a lack or excess of these elements may have serious clinical implications [2].

A tooth’s structure includes hard tissue (enamel, dentine, and cement) as well as soft tissue (pulp and periodontal ligaments). A tooth has a multicellular structure that can collaborate with the maxillofacial region functionally [2, 3].

Trace elements (TEs) are essential for human health. Toxic effects are caused by a lack of or an overabundance of TEs. TEs have a huge impact on both human and dental health. It is involved in the functions of essential biological polyphosphate compounds such as ATP, DNA, and RNA. In the tooth structure, TEs are found in various concentrations. Teeth are affected by changes in the density of certain TEs. Caries susceptibility is increased when the density of certain TEs is altered. Others function as a barrier to the development of caries. Zinc (Zn), phosphorus (P), and magnesium (Mg) are common TEs that have a significant impact on dental health. The use of tissue samplings such as blood, semen, teeth, nails, and hair to measure TE values in order to define and correct these effects has a significant impact. Teeth are widely regarded as a reliable indicator of TEs. As a result, TEs have a big impact on the development of healthy teeth [4].

2. Trace elements in dental hard tissues

The hard tissue that protects the tooth’s surface is known as enamel. This layer’s job is to protect the dentine-pulp complex. Enamel is the body’s toughest and most resistant tissue. It’s made up of 95–97% inorganic material (calcium hydroxyapatite crystals) and 1–2% organic material (proteins like amylogenic, enameline, ameloblastin, and tuftelin, to name a few), and 2–4% water [5]. TEs make up a small percentage of the 97 percent inorganic content and consists of Phosphorus (P-17%), calcium (Ca-36.5%), fluoride (F-0.016%), 3.0% carbon dioxide, 0.2% Na, 0.3% potassium (K), 0.016% Fluoride, 0.1% sulfur (S), 0.01% copper (Cu), 0.016% Zn, 0.003% silicon (Si); and low amounts of silver (Ag), strontium (Sr), barium (Ba), chromium (Cr), manganese (Mn), Vanadium (V). TE is deposited in human tooth enamel by the environment before and after the tooth’s mineralization and maturation [6].

After Enamel, the next layer to the tooth is Dentin consists of an inorganic matrix 70% in weight (40–45% in volume) Organic matrix 20% by weight (30% in volume), and water 10% by weight (20–25% in volume). The organic portion consists of proteins like osteonectin, osteopontin, osteoclastin-like dentin Gla protein, dentin phosphorene, dentin matrix protein, and dentin sialoprotein and type I collagen fiber [6, 7]. The inorganic material consists of hydroxyapatite crystals and TEs (40 in number) which include Zn, Sr., Fe, Al, B, Ba, Pb having up to 1000 ppm concentration and Ni, Li, Ag, As, Se, Nb, Hg having 100 ppb concentration. An analysis of the relation with age of 10 trace elements in dentine found that boron (B), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn), rubidium (Rb), strontium (Sr), molybdenum (Mo), cadmium (Cd), and lead (Pb) and suggested that human dentine is an appropriate substance for relating sex and age [8].

3. Cementum

Cementum is a type of connective tissue that connects the periodontal ligament to the root surface and covers the root surface’s outermost layer of calcite matrix [9]. Cement is a vascularized, mineralized tissue and has higher regeneration potential. It connects the dentin to the periodontal ligament and aids in the repair and regeneration of periodontal tissue after injury [10]. Cement’s inorganic portion is identical to that of bone, dentin, and enamel.

The essential mineral part of cementum consists of calcium hydroxyapatite with amorphous calcium phosphate (Ca10 (PO4) 6 (OH) 2) and has a lower crystallinity than other calcifying tissues [11]. This lower crystallinity causes the cementum, to be easily decalcified and increases the tendency to absorb nearby ions like fluoride. That’s why a higher concentration of fluoride is found in cementum ad compared to other parts of the tooth. In comparison to other calcifying tissues, the cement of adult mature teeth has higher fluoride content. The amount of magnesium in the cement is about half that of the dentin. In the deep layers of the cement, Mg levels gradually rise [9, 10].

4. Dental pulp

Dental pulp consists of Odontoblastfibroblast (collagen and elastic fibers forming cells), blood vessels, nerves, and lymphatic vessels that make up the tooth pulp that develops from the dental papilla [11]. The cells which are responsible for the formation of pre-dentin, dentin, and reparative dentin are Odontoblast [11]. When the pulp’s health is threatened the pulp cells especially fibroblasts produce inflammatory mediators such as IL-8, IL-6, and vascular endothelial growth factors that are responsible for producing symptoms of pulp infection. The tooth pulp is responsible for a variety of biological functions, including nutrition, sensitivity, building, and defense. The health of the pulp is largely influenced by changes in blood pressure and arterial flow in the apical area. When tooth pulp is affected by stimulus or irritants like mechanical, chemical, thermal, or microbial agents causing vascular inflammatory responses like local tissue reactions and lymphatasis(affecting lymphatic drainage of pulp area) [12, 13, 14].

Dental caries is a microbiological infectious disease that causes the degradation of calcified tissues and the destruction of the organic part of the tooth leads to cavitation. The bacteria (from mutans Streptococci and Lactobacillus species), a susceptible tooth surface (host), and a nutrient (diet) to provide bacterial growth are all needed for the formation of dental caries. From enamel, caries progress to dentin and causes inflammation of the pulp [15, 16].

In a systematic review analysis of various studies assessing the role of trace elements in oral health, it was found that there are some trace elements that cause dental caries progression whereas certain trace elements may decrease the risk of developing dental caries [4].

The effects of fluoride and various trace elements on dental hard tissues are as follows:

1. Fluoride as trace element

Of the existing anticaries agents, fluoride is the most powerful and well-tested. Understanding the mechanism of fluoride’s action in the prevention of dental caries is critical for developing the best fluoride delivery systems for optimal caries reduction. Although the exact and full mechanism of action of fluoride cannot be determined at this time, there is enough evidence to suggest that fluoride has a number of subtle effects on the calcium-phosphate system as well as the dental plaque metabolism. Fluorides can affect calcium-phosphate interactions in tooth enamel during the mineralization stage (before the tooth emerges) and, also, post eruptively by surface interactions with enamel, as well as during a carious attack [17, 18].

• Mineral phase of enamel - a review

Ca2+, PO43-, OH-, and carbonate are the key chemical components of tooth enamel (CO3²⁻). These components are found in the form of microcrystals in enamel and dentin, and their spatial structure resembles that of the pure ternary mineral hydroxyapatite, Ca10(PO4)6(OH)2. Carbonate is a component of enamel’s relatively large apatite crystals. Furthermore, teeth’s mineral phase contains a variety of trace elements, the most significant of which is fluoride. Some of the elements are adsorbed on the surface of hydroxyapatite crystals, while others with the right size and charge will fill voids or replace calcium or phosphate in the crystal interior. As a result, it’s obvious that enamel bioapatite is not pure apatite, but rather includes CO32-, Na+, Mg2+, F-, Sr2+, CI-, and other ions. Enamel apatite deviates from the stoichiometry of pure apatite in terms of Ca/P ratios due to a large number of substitutions in the crystal lattice. Enamel crystals also have a lot of flaws and are low in calcium and hydroxyl ions. The solubility of enamel tends to increase as voids and deviations from stoichiometry increase [19].

Fluoride incorporation within the apatite lattice has significant consequences. The formation of fluorapatite is caused by the replacement of hydroxyl groups by smaller fluoride ions, which causes a decrease in the dimension of the unit cell and has many effects on the physical and chemical properties of the crystals. Surface enamel (first 10 um) obtained from people living in fluoridated areas may contain 3000–4000 ppm of fluoride, whereas pure fluorapatite has a fluoride concentration of 38,000 ppm. It is clear that drinking fluoridated water causes just a small amount of fluoride ions to be substituted for hydroxyl ions, around 10%. Even this minor substitution appears to play a role in the strong cariostatic impact. The acquisition of fluoride by enamel is considered before exploring the mechanisms of fluoride action [19, 20, 21, 22].

• Acquisition of fluoride in enamel

Fluoride enters dental enamel by two mechanisms: (1) systemically, through absorption of fluorides in water, drinks, foods, or fluoride supplements, and (2) topically, through oral fluids such as saliva, urine, plaque fluid, and topical fluoride solutions bathing enamel. Topical fluoride acquisition is limited to the enamel surface, mostly the first 10- to 30-pm layer, and is often limited to etched surfaces and incipient lesions.

• Systemic acquisition of fluoride

During the mineralization process, fluorides are introduced pre-eruptively into enamel from tissue fluid. The fluoride level acquired is determined by the fluoride concentration in the plasma, which is a feature of the fluoride consumed in water, food, or supplements. The fluoride concentration is relatively high during the early stages of enamel development, but it gradually decreases as the tooth matures and acquires more minerals [23].

During the pre-eruptively maturation period, when enamel undergoes rapid and more full mineralization, the majority of fluoride is incorporated into the sound surface of the enamel.

Since primary teeth have a shorter time of enamel maturation than permanent teeth, they absorb less fluoride. The slight variations in fluoride concentration between permanent teeth can also be explained by differences in tooth maturation time. In both fluoride and non-fluoride regions, a gradient concentration occurs with a declining concentration towards the dento-enamel junction in unerupted and erupted teeth [23].

While the majority of fluoride is acquired during the pre-eruptive growth of teeth, it is important to note that a large portion of the mineral component of enamel (about 10% in bovine enamel) is acquired during post-eruptive maturation [24].

Furthermore, the optimum value for enamel crystallinity is reached several years after the eruption. A significant amount of fluoride is introduced into surface enamel during this process of mineral deposition. Fluoride is less likely to disperse as teeth age and become more mineralized, so deposition is more limited to the surface. This causes a more pronounced fluoride concentration gradient, with lower concentrations towards the interior of enamel, though this is later decreased by abrasion on exposed areas of the tooth. The concentration of fluoride in populations that consumed water that was optimally fluoridated (1 ppm) during the development of the dentition is higher, Fluoride concentrations in total enamel of permanent teeth range from 200 to 300 ppm, with levels as high as 3000 ppm in the first 10 micrometer. The comparable fluoride concentration in non-fluoridated areas is about 150 ppm in whole enamel and under 2000 ppm in surface enamel. In the outer few micrometers of enamel, the gradient is very steep. These levels are lower in primary teeth, with fluoridated and non-fluoridated communities having 900 and 650 ppm in surface enamel, respectively [17, 25]. Fluoride concentration is the highest in surface enamel and decreases towards the inner parts. Fluoride concentrations in enamel vary from one surface to another on the same tooth. Fluoride concentrations in newly erupted tooth surface enamel are higher near the incisal edge than near the cervical margin [26]. However, after the eruption, subsequent wear and attrition of the enamel destroy the fluoride-rich outer enamel of the incisal edge at a faster rate than it is obtained, allowing it to fall below the cervical enamel.

Topical obtainment of fluoride is often acquired post-eruptively from the oral atmosphere in the enamel surface, but the accumulation is mostly limited to the surface. Foods, water, fluoride-containing beverages, toothpastes, mouth rinses, prophylactic pastes, topical solutions, and gels are all sources of fluoride.

• Mechanisms of Cariostatic Action

1. Fluoride’s Effect on Enamel Solubility- It is widely accepted that caries are caused by bacterial acids demineralizing the mineral phase of the tooth. As a result, the solubility of tooth minerals may have an impact on the caries process. A potential mechanism by which fluoride decreases caries is by influencing the solubility of dental enamel, according to these claims. It is relatively easy to show that trace amounts of fluoride (−1 ppm) in an acid buffer solution significantly reduce enamel solubility, and that enamel readily acquires reduced solubility properties when exposed to a fluoride solution.

   At pH 4.5, Ten Cate and Duijsters [27] found that 2 ppm F in a solution containing 2.2 mM Ca and P effectively prevented enamel demineralization. Proof that the slight rise of fluoride in enamel caused by drinking fluoridated water causes significant solubility differences is less conclusive.

   Isaac et al. and Jenkins [28, 29] Solubility tests of intact enamel obtained from teeth of individuals living in fluoridated and non-fluoridated areas show a trend towards less solubility in the fluoridated classes. Moreno et al. [30] used apatites with well-defined levels of fluoride ranging from 0 to 3.4 percent to come to the conclusion that fluoride concentrations of 4000–8000 ppm were required to produce a significant decrease in enamel solubility. Fluoride concentrations in the molecular layers of surface enamel in fluoridated zones can be higher than those detected by the normal imprecise methods of collecting outer enamel. Explaining how a restricted substitution of fluoride ions for hydroxyl ions in enamel apatite can affect enamel solubility requires another consideration. Low levels of fluoride in the solution can react with the outer surfaces of dissolving hydroxyapatite crystals, forming a shell with fluorapatite solubility properties, according to Brown et al. [22].

The presence of small amounts of fluoride during a carious attack may therefore have a major impact on the properties of enamel crystals. This may explain why fluoride-containing products (dentifrices and mouth-rinses) are highly effective cariostatic agents when used on a regular or weekly basis for long periods of time. As previously stated, substitutions and defects cause enamel apatite to deviate from the stoichiometry of pure hydroxyapatite. Fluoride stabilizes the crystal structure of enamel, while carbonate and sodium increase its solubility and reactivity. Also, Nikiforuk et al. [31] found some evidence that the presence of fluoride during enamel production results in lower carbonate content. The dissolved enamel crystals preferentially lose carbonate during an incipient carious assault. Crystals containing less carbonate are thought to have lower reactivity and solubility, making them more resistant to caries. Fortunately, as the plaque’s pH rises, recrystallization occurs, resulting in the formation of larger, more resistant crystals. The sum of these results is that fluoride has a slight but important effect on enamel solubility, even at the relatively low concentrations found in enamel.

1. Effect of fluoride on mineral phase crystal structure -As calcium phosphate precipitates from a saturated solution in the physiological pH range, the initial phase stoichiometry is typically less than the calcium/phosphate molar ratio (1.67) found in pure hydroxy-apatite. Brown et al. [22] found evidence that the initially formed solid phase is octacalcium phosphate, tricalcium phosphate, dicalcium phosphate, or a combination. The initial precipitate may also be an amorphous solid with no set calcium/phosphate ratio, according to some theories. Whatever the initial phase was like, it was transformed into hydroxyapatite and possibly some fluorapatite, the thermodynamically more stable phases under physiological conditions. Amjad and Nancollas [19] verified earlier work that fluoride at concentrations of 1–5 ppm enhanced the precipitation of the less soluble phase of calcium phosphate in very careful kinetic studies of calcium phosphate precipitation in the presence of fluoride ions. In the absence of fluoride, the phase that evolved first had the same stoichiometry as octacalcium phosphate. The Ca/P ratio of the solid phase increased in the presence of fluoride and matched that of fluorapatite. Evidence suggests that fluoride acts as a catalyst during mineralization, causing the more soluble precursor phases to transform into the thermodynamically more stable apatite. This in vitro process is active during tooth mineralization, as shown by the lower carbonate levels in enamel from fluoridated areas. Fluoride also favors the creation of more acid-resistant crystals during the demineralization-remineralization episodes that characterize carious attacks. Fluoride can be believed to stabilize the crystal structure of enamel apatite because of its ability to form a more stable apatite phase. It should be remembered that the lattice comprises columns of hydroxyl ions that are electrostatically bound to calcium ions. Some of the hydroxyl ions are still absent, and these vacancies reduce the crystal’s stability. Fluorides may fill these voids or act as a hydroxyl group replacement, forming a stronger bond to the lattice site than hydroxyl ions. The negatively charged fluoride forms a tight hydrogen bond with the oxygen atom of the adjacent hydroxyl groups. Additionally, the better match of fluoride ions between calcium ions increases the electrostatic attraction between fluorides and calcium, further stabilizing the structure. While this argument has not been corroborated, the fluoride ions’ strategic location may also prevent diffusion along the linear chain. Although this assertion has not been corroborated in synthetic hydroxyapatite with hydroxyl deficiencies similar to those found in enamel [Verbeeck et al.] [32], the strategic location of the fluoride ions can also obstruct diffusion along the linear chain. As a consequence of a small fluoride substitution in the lattice structure, the crystallinity and stability of the crystal are increased.

2. Effect of fluoride on enamel remineralization- Clinical remineralization and reversal of early carious lesions have been demonstrated experimentally in vivo [von der Fehr et al., 1970] and clinically observed [33]. Several researchers have recorded that fluorides improve this natural process in vitro [34, 35]. Salivary components and fluoride are now recognized as effective natural protection mechanism that allows enamel to respond to cariogenic challenges. In vitro, adding 0.05 mM fluoride to calcium phosphate solutions used to remineralize partially demineralized enamel increases the rate of remineralization by 4- to 8-fold [36]. In comparison to natural plaque, which has high fluoride levels, etched enamel remineralization results in higher fluoride levels in the enamel. This is referred to as enamel’s adaptative response to the acidic environment in a specific area [37]. The minerals that form during remineralization are less soluble than those that form in the same solution but do not contain fluorides.

   An important reservoir of fluoride is surface enamel from which fluoride is released during the demineralization phase of a carious attack. Fluoride ions are also released from plaque when the pH falls which may contribute to remineralization. The process of remineralization can function at the earliest stage of caries formation, i.e. when the first acid attack occurs.

   As the pH starts to grow after the acid attack, fluoride in the microenvironment will trigger enamel dissolution to stop sooner. If the pH increases, fresh, bigger, less soluble crystals form, containing more fluoride, such as fluoridated hydroxyapatite, and less carbonate like fluoridated hydroxyapatite. The enamel is partially remineralized as a result of the procedure. Following exposure to fluoride, saliva, or plaque fluid, the amount of new minerals at the site may increase even more. When fluoride is applied at a later stage of caries growth, such as when a white spot is apparent, fluoride penetrates the surface layer and is absorbed preferentially by the porous sponge like the body of the lesion. This also decreases the solubility of the lesion, making it more vulnerable to acid attacks in the future. On radiographs prepared from thin parts taken through the lesion, successive fluoride exposures and caries attacks often result in a laminated appearance [38]. According to in vitro remineralization tests, the entire body of the white spot lesion does not need to be remineralized to become covered. If only the surface zone of a lesion is remineralized, the lesion can be stopped. When lesions are subjected to re-mineralizing solutions containing relatively high amounts of fluoride or calcium, this is easily accomplished [34]. As a result, the appearance of natural caries white spots in the mouth does not always imply that the region is actually under attack by caries. It may actually signify a region that has been attacked but is now partly remineralized and arrested as a result. Because of the absorption of organic stains, long-standing arrested lesions often appear as brown spots [35].

   Because of the buffering effect of saliva and plaque, as well as the high concentrations of calcium and phosphate present, the caries process is complex, with periods of demineralization when plaque pH are minimal, alternating with periods of remineralization as pH rises. If the process is to be pushed in the direction of remineralization, the presence of trace amounts of fluorides released from enamel or normally present in plaque fluid is important [39]. This is a key mechanism by which fluoride decreases the incidence of caries.

3. Effect of fluoride and tooth morphology - Fluoride intake can affect the size and morphology of teeth in humans and laboratory animals. Most studies show that if fluoride is present during tooth development, diameters and cusp depths are smaller [40]. Such morphological modifications would help to reduce caries vulnerability by making teeth more self-cleaning, but it’s unclear if the effects of optimal fluoride intake are substantial enough to be clinically significant. Other trace elements (strontium and molybdenum) have similar effects in rats, raising questions about the fluoride effect’s specificity. According to Aasenden and Peebles [18], molars. Molars in subjects who consumed fluoridated water or nutrients had shallower fissures and less carious lesions than molars in a non-fluoride control sample, according to Aasenden and Peebles [18], corroborating other clinical impressions. Deep fissures collect more plaque and are more difficult to clean than shallow fissures. The improved morphology of the occlusal surface may be partly to blame for the lower level of occlusal caries observed in fluoridated areas, despite the fact that it is the least affected.

5. Distribution of trace elements other than fluoride in dental hard tissue and its mechanism of action

As per the various literature, it has been found that various trace elements have different roles in causing and preventing dental caries like Selenium, Cadmium, Magnesium, Platinum, Lead and Silicon are caries promoting elements whereas other than Fluoride, Phosphorus, Molybdenum Vanadium, Strontium and Lithium are cariostatic elements.

The effects of trace elements on oral dental tissues are as follows-.

5.1 Vanadium (V)

The vanadium is found with industrial resources such as oil refineries and power plants. The majority of food compounds contain lesser concentrations whereas Seafood has a higher concentration of Vanadium and daily uptake from all source’s ranges from 0.01–0.02 mg [41].

Various studies have been done to assess the role of Vanadium in the development of prevention of dental caries. It’s found to be caries protective in animal studies and studies on rats but on the contrary studies on monkeys when they drank water with Vanadium content tend to have more carious lesions in their mouth. So exact role in the prevention and development of caries is still not clear [4].

5.2 Strontium (SR)

Strontium is universally present in the environment. Though it is non-essential but still present in all living beings. This element bears a resemblance to Calcium as it has a tendency to be taken by bones and skeleton. Depending upon the amount received, it can have beneficial and harmful effects on humans [42].

Strontium is considered to be caries protective as per the literature. The strontium makes the enamel more stable and stronger as compared to pure calcium content. It also found that remineralized process in enamel with strontium in solution easier and faster as compared to without strontium solution and because of this the tooth enamel stable and more resistant to caries and acid attack [43].

The epidemiological studies suggest that high strontium content is associated with decreased carious lesions or good enamel. The strontium content decrease with age and is found to be more young as compared to older people.

5.3 Lithium (Li)

Lithium has an inverse relation with the development of dental caries. Various studies reported with reduced incidence of caries in presence of lithium in humans [4]. Mostly the lithium exposure occurs with drinking water and if in excess can have an effect on different tissues or organs in animals like affects the thyroid function and also causes histopathological changes in salivary glands [44]. It has medicinal use in various psychiatric disorders like bipolar disorders [45].

5.4 Copper (Cu)

Copper is a component of a variety of metalloenzymes that act as oxidases to reduce molecular oxygen. Adult men and women should consume 900 g of fiber per day. Copper intake from food is approximately 1.0 to 1.6 mg/day for adult men and women in the United States. Adults have a Tolerable Upper Intake Level (UL) of 10,000 g/day (10 mg/day), a value based on protection from liver damage as the critical adverse effect. Greater amounts of copper are found in seafood, green leafy vegetables, animal products, pulses, and grains [46].

Oral Health and Diseases: What Role Does It Play- Hypochromic anemia, neutropenia, hypopigmentation of hair and skin, irregular bone structure with skeletal fragility and osteoporosis, joint pain, reduced immunity, vascular aberrations, and kinky hair are all signs of copper deficiency [47].

• If a person has copper deficiency for a long-time during stages of active growth it can cause anemia and abnormal keratinization of oral soft tissues. Reduced iron oxidation and decreased ferroxidase activity of ceruloplasmin are responsible for the anemic impact [48].

• Infections: Due to the accompanied neutropenia, lowered immunity can result in a variety of oral infections [49]. Granulocyte maturation disorder has been observed in the bone marrow, as well as vacuolation in neutrophils.

• Bone defects and pain due to abnormal functioning of ascorbate and lysyl oxidase leads to osteoporosis like changes in the body i.e. lack of trabecular pattern and cortex thinning.

• Oral lesions: according to several reports, the average serum copper levels were present in the Sera from patients with oral potentially malignant conditions like oral leukoplakia and oral submucous fibrosis, as well as malignant tumors like squamous cell carcinoma, and was substantially higher.

• The average copper intake in India is 2.1–3.9 mg/day, but it is more than 5 mg/day due to areca nut chewing. Copper released from areca nuts during chewing is thought to come into direct contact with the oral epithelium and be dissolved in saliva. Copper is said to be found in saliva for up to 30 minutes. The longer copper is present in saliva, the more likely it is to be absorbed by the oral epithelium [48]. Copper occurs in the blood after 15 minutes of ingestion of areca nut and its ingredients, according to some [50]. Cu serum levels steadily rise in patients with oral submucous fibrosis as the condition progresses clinically. However, the local impact of increased salivary copper levels may be more significant than the increased serum levels. Other schools of thought attributed a decrease in copper serum concentrations to copper’s role in upregulating lysyl oxidase, which resulted in excessive collagen cross-linking [51].

• Cu is also thought to have a caries-promoting effect [52].

5.5 Selenium (Se)

Selenium salts are essential for a variety of cellular functions in the human body, but too much of them is toxic [53]. It is present in the liver, kidneys, seafood, poultry, grains, grain oils, milk, fruits, and vegetables, and a maximum intake of 70 micrograms is recommended [54]. It is required for the formation of anti-oxidants enzymes in the body.

Selenium is a non-metallic substance that occurs naturally and is absorbed by the body through food or inhalation. Intake of selenium was linked to an increase in dental caries. It has been stated that selenium settles in the enamel’s micro-crystal structure at the start of decay, making it more susceptible to dissolution [54].

Furthermore, a reduction in selenium levels in the body has been linked to oxidative stress. According to a new study, patients who developed oral mucositis as a result of high-dose chemotherapy significantly shortened the duration and severity of the condition and also has cytoprotective impact and antiulcer activity on subsequent reinforcement [55].

5.6 Manganese (MN)

The amount of manganese in food varies greatly. Peanuts and grains have the highest concentrations, while milk products, meat, poultry, fish, and sea products have the lowest. Manganese can also be present in coffee and tea, which account for 10% of daily intake. On average, an adult’s body contains 15 mg of manganese, which is often found in nucleic acid. The regular requirement is between 2 and 5 milligrams. Manganese is a component of metalloenzymes and acts as an enzyme activator. Manganese concentrations range from 0.3 to 2.9 ug manganese/g in all mammalian tissues. Tissues with a lot of mitochondria and pigments (like the retina and dark skin) have a lot of manganese concentrations in them.

Manganese is a TE that can be ingested by food, air, or water and incorporated into the enamel. Furthermore, Mn has the ability to change Ca′s position at HAP. Mn can be used in synthetic HAP without degrading the crystal area size, according to several studies [56].

Manganese concentrations are normally higher in bones, livers, pancreas, and kidneys than in other tissues. The bones are the most valuable manganese shop. Manganese is one of 49 elements found in enamel hydroxyapatite crystals, and it is normally present in very small amounts. Manganese concentrations in enamel range from 0.08 to 20 ppm, or 0.08–20 mg/kg, and in dentine from 0.6 to 1000 ppm. The concentration of Mn is higher in permanent dentition compared to primary dentition [57].

Manganese is being increasingly linked to the occurrence of tooth decay. According to one study, the incidence of dental caries in males increased in areas with higher manganese content. As a result, it is stressed that manganese promotes caries [4].

5.7 Zinc (ZN)

Zinc is found in the human body in amounts ranging from 2 to 4 grams. The prostate, eyeballs, brain, muscles, bones, kidney, and liver all store zinc. It is the only metal used in all enzyme groups and is the second most common transition metal in species after iron. The concentration of Zn in plasma (10%) remains constant even when intake is higher and in plasma 60% is tightly bound to albumin and the rest to transferrin (40%) [58, 59].

The RDA of Zinc is 15–20 mg. The pancreas and intestines excrete approximately 2–5 mg per day. Pregnancy, loss of liquid, oral contraceptive use, blood loss, and acute infection all having lower plasma zinc levels.

Zinc is needed for cell reproduction, differentiation, and metabolic functions. Zinc also aids normal development during pregnancy, infancy, and adolescence [60, 61]. Zinc is present primarily in animal products such as beef, milk, and fish. Phytonutrients are poor in zinc bio adjustment [58].

Oral Health and Diseases: What role does it play?

1. Zinc is present in the oral cavity i.e. in Enamel, Dentin, and Plaque (Naturally present). Oral health products containing zinc are used to regulate plaque, minimize odor, and delay the development of calculus. Following delivery from mouth rinses and toothpaste, zinc elevated concentrations in plaque and saliva can be retained for long periods of time. Despite the fact that low concentrations of zinc can both minimize enamel demineralization and alter remineralization, the anti-cariogenic efficacy is still debatable and contradicted by numerous studies [62].

2. Taste disorders: Zinc plays an important role in taste functions at different stages of organization, including taste buds, taste sense nerve transmission, and anatomical structures like the brain. Early researchers concluded that taste disruptions are caused by zinc deficiency due to some etiology, and therefore zinc depletion is still corrected for patients reporting taste imbalances [63].

3. A rodent study found that a zinc-deficient diet can cause parakeratosis of the normally ortho-keratinized oral mucosa. As a result, zinc deficiency can be a risk factor for periodontal and oral diseases and causes parakeratosis in soft oral mucosa like in cheeks, tongue, and food pipe [64].

4. Act as a cofactor for superoxide dismutase enzyme and zinc deficiency is a finding of patients with potentially premalignant lesions such as oral leukoplakia that could be due to more intake of zinc in reaction to higher copper found in arecanut and oxidants produced during tobacco usage [65, 66].

5. In contrast to common opinion, limited evidence indicates that zinc has a carcinogenic effect [67].

5.8 Cadmium (Cd)

Cadmium accumulates in the liver and bones as soon as it reaches the body and is released slowly (cadmium reference). It causes a major environmental issue as a result of being received by plants and entering the food chain, or as a result of being washed from the soil and hitting the water environment. Furthermore, chelating agents accelerate the downward carriage of cadmium from the soil, which can contribute to contamination of drinking and irrigation waters as it reaches underground water bodies [68, 69].

Exposure to cadmium has been linked to a number of health problems, including kidney failure and skeletal problems, and heart diseases [70]. It can be released from dentures and materials containing metal alloys in the mouth (rigidly bound with metallothioneins) and can accumulate in teeth and other oral tissues.

Cadmium has been linked to an increase in the occurrence of tooth decay. However, it is said that cadmium settlement in teeth after growth is ineffective in preventing caries. According to some animal studies, there is a clear connection between the formation of dental caries and cadmium intake during the dental growth period [4]. The power of increased exposure to and diffusion of this toxic material on the general and oral health of vulnerable populations such as children is fetching increasingly significant [4].

5.9 Lead (Pb)

Lead may be consumed by tainted food and beverages as a result of industrial activity [51]. Lead enters the food chain through vegetables grown in polluted soil, for example. Lead can be transferred from polluted soil to plants and grass, potentially resulting in toxic metal accumulation in vegetating ruminants, especially cattle. Lead accumulation causes toxic effects in animals, as well as toxic effects in people who drink toxic metal-contaminated meat and milk [71].

It is a radioactive metal that is harmful to the human body. At the HAP of teeth, lead has the potential to translocate with Ca + 2 and resulting in decreasing the size of hydroxyapatite crystals [72].

In the atmosphere or diet, lead is passed to body hard tissues such as teeth and might be having an effect on increasing dental caries. Furthermore, it has been discovered that lead promotes the development of enamel hypoplasia. As per the literature, it shows have a probable connection between increasing lead levels in saliva and the formation of dental caries in children with early tooth decay. As a result, lead is critical in the formation of new caries lesions [4, 72, 73].

5.10 Iron (Fe)

Iron (Fe) is abundant in nature and a biologically important part of all living organisms, unlike other TE. Regardless of geological abundance, when oxygen comes into contact with iron, it forms hardly soluble oxides. As a result, it is poorly absorbed by species [74].

Iron is found in liver, beef, poultry products, and fish, as well as cereals, green leafy vegetables, pulses, nuts, oilseeds, and dried fruits. Iron, as an important nutrient, is primarily absorbed by green vegetables. Enamel has been found to have low iron concentrations [75]. RDA ranges from 4 to 5 gm and is essential to maintain a healthy body.

6. Detection of trace elements and assessment of nutritional status

This was done as follows:

1. Despite the fact that different methods have been used to assess the existence of trace elements, due to their large distribution within living tissues and enzyme systems, it is a time-consuming and fruitless task. To determine the sum of trace elements, colorimetric and spectrographic methods are widely used. For solitary element analysis, spectroscopy and electrochemical methods are typically used, while for multiple-element analysis, neutron activation analysis and spectroscopic methods are typically used [76].

2. Iron deficiency can be easily diagnosed routinely by laboratory test like Complete blood count with having the high total iron-binding capability, a low serum iron level, and a low serum ferritin concentration. The erythrocyte zinc porphyrin assay, has recently been used in primary screening for determining iron status [77, 78].

3. The optimum copper-zinc plasma or serum ratio has been stated to be 0.70–1.00. As previously mentioned in the report, diagnosing zinc deficiency is a difficult task. The most popular indices for measuring zinc deficiency are plasma or serum zinc levels [79, 80].

4. Since tissue chromium stores do not appear to accurately represent blood chromium, serum chromium concentration is not an accurate measure of chromium status. The existence of an extreme chromium deficiency is thought to be indicated by serum chromium levels less than 0.14–0.15 ng/mL. A person’s serum chromium level may be elevated as a result of excessive chromium exposure from work or an accident.

5. The nutritional status of selenium has been determined using various tissues such as blood, hair, and nails. In general, if dietary selenium consumption is consistent, these tissues may provide a reliable assessment of selenium status.

6. It is difficult to assess the status of other trace elements in typical individuals’ tissue levels.

7. Sources of trace elements

The location of trace elements on dental hard tissue like enamel and dentin may differ and also within the structure. The Cu, Pb, Co, Al, I, Sr., Se, Ni, and Mn more on enamel whereas Fe and F more on dentin and cementum.

Also, within the enamel, the outer surface has more Iron, Lead, and Manganese than inside layers suggesting that mostly these come from the external environment and get deposited on tooth enamel after an eruption or during calcification.

Trace elements can reach the human body through a variety of routes, including food, water, and air. Dental materials and fluids (such as saliva, dental prosthesis, and dental porcelain) are discussed below as potential sources of trace elements in tooth enamel [81].

1. Saliva - Saliva is actively washing teeth. The structure of the enamel surface is considered to be affected by many trace elements present in saliva. It varies among the population and in a great amount the trace elements found in enamel and also found in saliva (Na, Mg, K, and Zn). The amount of trace elements in one’s saliva varies from person to person. The most abundant trace elements in saliva are also the most abundant trace elements in tooth enamel (Na, Mg, K, and Zn and it suggests that saliva can have a profound effect on enamel demineralization and remineralization.

2. Dental prostheses - Partial dentures can be a source of trace elements discovered in teeth. Patients with partial dentures have higher levels of Cr, Co, Fe, and Ni in their saliva than patients without partial dentures. As a result, the accumulation of trace elements in tooth enamel can be affected by the presence of dentures in the mouth. The effect of trace elements presents in dental prostheses on tooth enamel will be confirmed in future studies.

3. Dental porcelain - This material consists of a glass matrix and a leucite crystallite phase. It contains minerals like Si (57–66%), B (15–25%), Al (7–15%), Na (7–12%), K (7–15%), and Li (0.5–3%). The concentrations of these elements in tooth enamel were found to be closely associated. This finding suggests that dental porcelain may be another potential source of these elements in tooth enamel but need to confirm with future studies.

8. Conclusion

Though trace elements are only needed in trace amounts, their optimal presence is critical for the body’s normal physiological functioning and for upholding the body’s biodynamics. Excess and deficiency both contribute to the onset, development, and promotion of different disease processes. As a result, having a thorough understanding of these trace elements is critical for disease prevention and optimum health.

Nutritional and clinical diagnosis of trace element defects is one of the most daunting activities. Deficient intake of an important trace element can cause significant biological functions within tissues to be harmed, and restoring physiological levels of that element can restore or prevent that function from being harmed. The amount of main trace metals circulating in the blood and deposited in cells is controlled and regulated by an intricate mechanism in the human body. When the body fails to function properly or there are inappropriate levels in dietary sources, excessive levels of these trace elements may develop. A diet rich in antioxidants and essential minerals is essential for a healthy mind and body, according to numerous lines of proof. In recent years, preventive medicine has gotten more coverage than anything else, as the adage goes, “prevention is better than cure.” Oral and general health are inextricably linked, and the oral cavity can effectively reflect systemic health. Oral diseases such as oral leukoplakia, oral submucous fibrosis, oral cancer, and others have been treated with a mixture of micronutrients and trace elements because their combined effect is more effective than a single application. As a result, general and oral healthcare professionals must be familiar with the clinical aspects of trace elements.