review article nutritional aspects of essential trace elements in...

Review ArticleNutritional Aspects of Essential Trace Elements in Oral Healthand Disease An Extensive Review

Preeti Tomar Bhattacharya1 Satya Ranjan Misra2 and Mohsina Hussain1

1Department of Oral Medicine and Radiology Haldia Institute of Dental Sciences and Research Haldia West Bengal 721645 India2Department of Oral Medicine and Radiology Institute of Dental Sciences Bhubaneswar Orissa 753001 India

Correspondence should be addressed to Preeti Tomar Bhattacharya preeti kgmurediffmailcom

Received 31 December 2015 Accepted 31 May 2016

Academic Editor Susana Zeni

Copyright copy 2016 Preeti Tomar Bhattacharya et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Human body requires certain essential elements in small quantities and their absence or excess may result in severe malfunctioningof the body and even death in extreme cases because these essential trace elements directly influence the metabolic and physiologicprocesses of the organism Rapid urbanization and economic development have resulted in drastic changes in diets with developingpreference towards refined diet and nutritionally deprived junk food Poor nutrition can lead to reduced immunity augmentedvulnerability to various oral and systemic diseases impaired physical andmental growth and reduced efficiency Diet and nutritionaffect oral health in a variety of ways with influence on craniofacial development and growth and maintenance of dental and oralsoft tissues Oral potentially malignant disorders (OPMD) are treated with antioxidants containing essential trace elements likeselenium but even increased dietary intake of trace elements like copper could lead to oral submucous fibrosis The deficiency orexcess of other trace elements like iodine iron zinc and so forth has a profound effect on the body and such conditions are oftendiagnosed through their early oral manifestations This review appraises the biological functions of significant trace elements andtheir role in preservation of oral health and progression of various oral diseases

1 Introduction

Appropriate nutrition of all the metabolically active cells andtissues is essential for preserving health of the human body asa whole Micronutrients including trace elements vitaminsand antioxidants play a vital role in continuously occurringregenerative processes coping with ongoing oxidative stressin the body tissues and sustaining ample immunity againstpathogens [1 2]Themanifestations of undernutrition as wellovernutrition of micronutrients on the oral health are vastand can result in defects of the dental hard tissues as well asoral mucosa [3 4]

The word ldquotrace elementsrdquo is used for elements existingin natural and perturbed environments in small amountswith excess bioavailability having a toxic effect on the livingorganism [5] Trace elements are chemical micronutrientswhich are required rather in minute quantity but play avital role in maintaining integrity of various physiologicaland metabolic processes occurring within living tissues

The deficiency of any of the trace elementsmay be apparent asa combination of various clinical manifestations rather than aspecific presentation as each trace element is related to manyenzyme systems

Healthy nutritional habits with regular intake of essentialvitamins andminerals are of immense significance to generalas well as oral health As there had been limited knowledgeamong the oral physicians regarding significance of traceelements in human nutrition the current review focuses onthe role of those essential trace elements which have a provenrole in maintaining oral health and their implications invarious oral diseases and disorders

2 Classifications of Trace Elements

Limited attempts have been made for classifying trace ele-ments solely The classifications which address the presenceof trace elements have been listed

Hindawi Publishing CorporationScientificaVolume 2016 Article ID 5464373 12 pageshttpdxdoiorg10115520165464373

2 Scientifica

21 WHO Classification 1973 [6] As per this classificationnineteen trace elements have been divided into three groups

(1) Essential elements zinc (Zn) copper (Cu) selenium(Se) chromium (Cr) cobalt (Co) iodine (I) man-ganese (Mn) and molybdenum (Mo)

(2) Probably essential elements(3) Potentially toxic elements

22 Friedenrsquos Classification of Elements In 1981 Frieden pro-posed a biological classification of trace elements based ontheir amount in tissues [7]

(1) Essential trace elements boron cobalt copperiodine iron manganese molybdenum and zinc

(2) Probably essential trace elements chromium fluo-rine nickel selenium and vanadium

(3) Physically promotive trace elements bromine lith-ium silicon tin and titanium

23 Friedenrsquos Categorical Classification of Elements [8]Twenty-nine types of elements present in the human bodyhave been classified into five major groups as follows

(i) Group I basic components of macromolecules suchas carbohydrates proteins and lipids Examplesinclude carbon hydrogen oxygen and nitrogen

(ii) Group II nutritionally important minerals alsoreferred to as principal or macroelements The dailyrequirement of these macroelements for an adult per-son is above 100mgday Examples include sodiumpotassium chloride calcium phosphorous magne-sium and sulfur

(iii) Group III essential trace elementsThe trace elementsare also called minor elements An element is con-sidered a trace element when its requirement per dayis below 100mg The deficiency of these elements israre but may prove fatal Examples include copperiron zinc chromium cobalt iodine molybdenumand selenium

(iv) Group IV additional trace elements Their role isyet unclear and they may be essential Examplesinclude cadmium nickel silica tin vanadium andaluminumThis group may be equivalent to probablyessential trace elements in the WHO classification

(v) Group V these metals are not essential and theirfunctions are not known They may produce toxicityin excess amounts Examples include gold mercuryand lead This group is equivalent to potentially toxicelements defined in the WHO classification

3 Discussion

An extensive and complex system is functioning inside thehuman body tomanage andmaintain the amount of essentialtrace elements within a normal range Micronutrients from

diet are transported into the blood if there is deficiencyenter cells if cellular levels are not adequate or are excretedif blood and cell levels are satisfactory or elevated Variousessential trace elements along with nutritional requirementand dietary sources have been listed in Table 1

31 Copper Copper is the thirdmost abundant trace elementwith only 75ndash100mg of total amount in the human body[9] Copper is present in almost every tissue of the bodyand is stored chiefly in the liver along with the brain heartkidney and muscles [10] Copper is absorbed in the gut andtransported to the liver In human blood copper is principallydistributed between the erythrocytes and in the plasma [11]It is transported in the form of ceruloplasmin into the plasmawhere its metabolism is controlled and is excreted in bile [12]Ceruloplasmin accounts for 90 of the copper content inblood and is responsible for carrying copper to the deficientcells [13] Copper-zinc metalloenzyme superoxide dismutasecontains 60of the copper in erythrocytes and the remaining40 is loosely bound to other proteins and amino acids

311 Biological Functions A significant number ofmetabolicenzymes function properly due to copper [13ndash16]The biolog-ical functions of copper have been listed [14ndash16]

(1) The enzyme cytochrome c oxidase comprising cop-per and iron plays a vital role in energy productionduring aerobic respiration

(2) Copper is also present in superoxide dismutase whichdetoxifies superoxides by converting them to oxygenand hydrogen peroxide

(3) Copper is also a component of lysyl oxidase whichtakes part in the synthesis of collagen and elastinCopper is also essential for maintaining the strengthof the skin hair blood vessels and epithelial andconnective tissue throughout the body

(4) Cu plays a considerable role in the production ofhemoglobin Ceruloplasmin catalyzes the oxidationof iron which subsequently is necessary to bind to itstransport protein transferrin [12]

(5) Melanin production copper containing enzymetyrosinase converts tyrosine to melanin

(6) Myelin production Cu is also necessary for thesynthesis of phospholipids found inmyelin sheaths inperipheral nerves [13 16]

(7) Copper is also required for the production of thethyroid hormone thyroxine [13]

(8) Copper can act as both an antioxidant and a prooxi-dant As an antioxidant Cu scavenges or neutralizesfree radicals and may reduce or help prevent someof the damage they cause [16ndash19] Copper promotesfree radical damage to the tissues when it acts asprooxidant [20]

312 Role in Oral Health and Diseases The symptoms ofcopper deficiency are hypochromic anemia neutropenia

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Table 1 Showing trace elements their RDI RDA and UL in the body and rich dietary sources [64 66 83]

Trace elementRecommendeddaily intake(RDI)

Recommended dietary allowance(RDA) Tolerable upper intake level (UL) Dietary sources

Copper 2000 120583g

Children 1 to 3 years old340mcgday 4 to 8 years old440mcgday 9 to 13 years old700mcgday 14 to 18 years old890mcgdayMen and women aged 19 years andolder 900mcgdayPregnancy 1000 mcgdayLactation 1300mcgday

Children 1 to 3 years old 1mgday4 to 8 years old 3mgday 9 to 13years old 5mgday 14 to 18 yearsold 8mgdayAdults 19 years old and above(including lactation) 10mgdayPregnancy 8mgday

Oysters other shell fishwhole grains beansnuts potatoes organmeats (kidney liver)dark leafy greens driedfruits and yeast

Iron 18mg

Children 1 to 3 years old 7mgday4 to 8 years old 10mgday 9 to 13years old 8mgdayBoys 14 to 18 years old11mgdayGirls 14 to 18 years old 15mgdayAdults 8mgday for men aged 19and older and women aged 51 andolderWomen 19 to 50 years old18mgdayPregnant women 27mgdayLactating mothers 10mgday

Infants and children from birth tothe age of 13 40mgdayChildren aged 14 and adults(including pregnancy andlactation) 45mgday

Haem iron liver meatpoultry and fishNonhaem iron cerealsgreen leafy vegetableslegumes nuts oilseedsjaggery and dried fruits

Zinc 15mg

Infants and children 7 months oldto 3 years old 3mgday 4 to 8 yearsold 5mgday 9 to 13 years old8mgdayGirls 14 to 18 years old 9mgdayBoys and men aged 14 and older11mgdayWomen 19 years old and above8mgdayPregnant women 11mgdayLactating women 12mgday

Infants 4-5mgdayChildren 1 to 3 years old 7mgday4 to 8 years old 12mgday 9 to 13years old 23mgday 14 to 18 yearsold 34mgdayAdults 19 years old and above(including pregnancy andlactation) 40mgday

Animal food meatmilk and fishBioavailability of zinc invegetable food is low

Cobalt 6120583g

Infants 05mcgChildren 1ndash3 years old 09mcg 4ndash8years old 12mcg 9ndash13 years old18mcgOlder children and adults 24mcgPregnant women 26mcgLactating mothers 28mcg

Not known

Fish nuts green leafyvegetables (broccolispinach) cereals andoats

Chromium 120 120583g

Children 1 to 3 years old 11mcg 4to 8 years old 15mcgBoys 9 to 13 years old 25mcgMen 14 to 50 years old 35mcgMen 51 years old and above 30mcgGirls 9 to 13 years old 21mcg 14 to18 years old 24mcgWomen 19 to 50 years old 25mcg51 years old and above 20mcgPregnant women 30mcgLactating women 45mcg

Doses larger than 200mcg are toxicBest sources processedmeats whole grains andspices

Molybdenum 75 120583g

Children 1 to 3 years old17mcgday 4 to 8 years old22mcgday 9 to 13 years old34mcgday 14 to 18 years old43mcgdayMen and women aged 19 years andabove 45mcgdayPregnancy and lactation50mcgday

Children 300ndash600mcgdayAdults (including pregnancy andlactation) 1100ndash2000mcgday

Animal food livervegetables lentils driedpeas kidney beanssoybeans oats andbarley

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Table 1 Continued



Selenium 70120583g

Children 1ndash3 years old 20microgramsdayChildren 4ndash8 years old 30microgramsdayChildren 9ndash13 years old 40microgramsdayAdults and children 14 years old andabove 55 microgramsdayPregnant women 60microgramsdayBreastfeeding women 70microgramsday

The safe upper limit for selenium is400 micrograms a day in adults

Liver kidney seafoodmuscle meat cerealcereal products dairyproducts fruits andvegetables

Iodine 150120583g

Children 1 to 8 years old90mcgday 9 to 13 years old120mcgdayChildren aged 14 and adults150mcgdayPregnant women 209mcgdayLactating mothers 290mcgday

Children 1 to 3 years old200mcgday 4 to 8 years old300mcgday 9 to 13 years old600mcgday 14 to 18 years old900mcgdayAdults above the age of 19 includingpregnant and breastfeeding women1100mcgday

Best sources seafoods(sea fish and sea salt)and cod liver oilSmall amounts milkvegetables and cereals

FluorineIn drinkingwater 05 to08mg

Children 1 through 3 years old07mg 4 to 8 years old 1mg 9 to 13years old 2mg 14 to 18 years old3mgMen 19 years old and above 4mgWomen 14 years old and above(including pregnant orbreastfeeding women) 3mg

07ndash9mg for infants13mg for children 1 to 3 years of age22mg for children 4 to 8 years ofage10mg for children above 8 years oldadults and pregnant andbreastfeeding women

Drinking water foods(sea fish and cheese)and tea

hypopigmentation of hair and skin abnormal bone formationwith skeletal fragility and osteoporosis joint pain loweredimmunity vascular aberrations and kinky hair [21]

(1) Deficiency of Cu in diet for a prolonged periodespecially during stages of active growth leads toanemia and defective keratinisation in the oral cavity[22] The anemic effect is attributed to decreasedferroxidase activity of ceruloplasmin and reducediron oxidation [5]

(2) Infections lowered immunity can result in variousinfections of the oral cavity due to accompaniedneutropenia [23] Granulocytematuration disorder inthe bonemarrow and vacuolation in neutrophils havebeen noted [5]

(3) Bone abnormalities and pain bone changes in copperdeficiency include a loss of trabecular formation withthinning of the cortexTheremay be osteoporosis andoccipital horn formation due to functional impair-ment of copper-requiring enzymes such as ascorbateoxidase and lysyl oxidase in case of copper deficiency[10]

(4) Oral lesions various studies found that the meanserum copper levels were significantly higher in thesera of patients with oral potentially malignant dis-orders such as oral leukoplakia and oral submucous

fibrosis and also malignant tumors such as squamouscell carcinoma The average intake of copper in Indiais 21ndash39mgday whereas due to areca nut chewingit is more than 5mgday It has been postulated thatcopper released from areca nuts while chewing camein direct contact with the oral epithelium and isdissolved in the saliva Copper is reportedly presentin the saliva for as long as 30 minutes The longer thepresence of copper in saliva the higher the chancesof its uptake by the oral epithelium [24] It has beenadvocated that copper appears in the blood after15mins of ingestion of areca nut and its products[25] In oral submucous fibrosis patients the serumlevels of Cu gradually increase as the clinical stage ofthe disease progresses However local effect of raisedsalivary copper may have a more important role toplay than the raised serum levels Other schools ofthoughts appraised decrease in the copper serumconcentrations due to usage of copper in upregulationof lysyl oxidase leading to excessive cross linkage ofcollagen [26]

(5) Cu is also believed to possess caries promoting prop-erty [27]

32 Zinc There is 2ndash4 grams of Zn distributed throughoutthe human body [28] Zinc is stored in prostate parts of

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the eye brain muscle bones kidney and liver [29] It is thesecond most abundant transition metal in organisms afteriron and it is the only metal which appears in all enzymeclasses [28 30] In blood plasma Zn is bound to and trans-ported by albumin (60) and transferrin (10) [31] Sincetransferrin also transports iron excessive iron can reducezinc absorption and vice versa [32]The concentration of zincin blood plasma stays relatively constant regardless of zincintake

321 Biological Functions Zinc functions in biology arenumerous but can be separated into three main categoriescatalytic regulatory and structural roles It is required forthe catalytic activity of a large number of enzymes [33 34] Itplays an important role in immune function wound healingprotein synthesis DNA synthesis and cell division [34ndash36]Zinc is required for proper sense of taste and smell [37 38]It also supports normal growth and development duringpregnancy childhood and adolescence [39ndash42] Allegedlyit also possesses antioxidant properties and thus may play arole in speeding up the healing process after an injury andprotecting against accelerated aging [40 43] Zinc ions areeffective antimicrobial agents even at low concentrations

322 Role in Oral Health and Diseases The roles of zinc inoral health and diseases are summarized as follows

(1) In the oral cavity zinc is present naturally in plaquesaliva and enamel Zinc is transformed into oralhealth products to control plaque reduce malodorand retard calculus formation The zinc elevatedconcentrations can be sustained for prolonged peri-ods in plaque and saliva following delivery frommouthrinses and toothpastes Although low concen-trations of zinc can both reduce enamel demineralisa-tion and modify remineralisation the anticariogenicefficacy is yet disputable and not supported by variousresearches [44]

(2) Taste disorders the role of zinc in taste functions isappreciable at various levels of organization such astaste buds the taste sense nerve transmission andbrain Zinc plays an important role in cell struc-ture architecture maintaining the cell membraneintegrity and functions of various cytoplasmic andmembrane enzymes Early researchers concluded thatzinc deficiency secondary to any etiology leads to tastedisturbances and thus still zinc depletion is correctedfor patients reporting with taste imbalances [45]

(3) A study conducted on rodents concluded that zinc-deficient diet can result in parakeratosis of normallyorthokeratinized oral mucosa Hence zinc deficiencycan be a potential risk factor for oral and periodontaldiseases The parakeratotic changes in cheek tongueand esophagus are a sign of zinc deficiency Thicken-ing of the buccal mucosa is a common manifestationalong with loss of filiform papillae [46]

(4) As stated above zinc is a cofactor for superoxidedismutase enzyme and various studies have shown

lower levels of serum zinc in patients with potentiallypremalignant disorders like oral leukoplakia Thismay be due to consumption of zinc in counterreaction to high content of copper in areca nut oroxidants released during tobacco usage [47]

(5) Similarly concentration of zinc in serum is signif-icantly decreased in oral squamous cell carcinomaand oral submucous fibrosis patients with history oftobacco consumption when compared to the controlgroup and gradually decreased with the duration ofthe habitThe serum level of zincwas reportedly lowerin oral squamous cell carcinoma patients than in oralsubmucous fibrosis patients [25 48]

(6) As transferrin transports both iron and zinc the levelof zinc increases as the level of iron decreases iniron deficiency patients Thus patients of OSMF alsosuffering from iron deficiency anemia show higherserum levels of zinc [25 48]

(7) Superoxide dismutase which is a natural antioxidantof the body is a Cu-Zn protein complex that hasan anticarcinogenic effect in OSMF Secondly zincdecreases the activity of copper containing lysyloxidase enzyme and thus causes inhibition of crosslinkage of collagen peptides It also plays a signifi-cant role in promoting collagen degradation throughcollagenase and matrix metalloproteinase Zinc thusbears an inverse relationship with copper and therebyinterferes with the mucosal absorption of copperExcess zinc particularly impairs copper absorption asboth metals are absorbed through metallothioneinsThe ratio of copper to zinc is also believed to be a reli-able biomarker in the development and progressiontowards carcinogenesis [48]

(8) On the contrary to the popular belief of protectivefunction of zinc limited literature suggests carcino-genic effect of zinc [49]

33 Iron Iron is the most abundant essential trace elementin the human body The total content of iron in the body isabout 3ndash5 g with most of it in the blood and the rest in theliver bone marrow and muscles in the form of heme [50]Iron is absorbed in the gut from diet in case of depletion andtransported in the form of ferritin Hemosiderin is a goldenbrownpigmentwhich is a byproduct ofmetabolismof ferritinand is deposited in the cells of the reticuloendothelial system[51] Homeostasis of iron maintains the iron levels in serumwithin normal range only by upregulation or downregulationof absorption mechanism of iron which is unique becauseit maintains homeostasis by regulating the absorption andnever excretion

331 Biological Functions Heme is themajor iron containingsubstance in ferrous or ferric state which is present inhemoglobin myoglobin and cytochrome There are numer-ous enzymes associated with iron namely cytochrome a-c p450 cytochrome c reductase catalases peroxidases

6 Scientifica

xanthine oxidases tryptophan pyrrolase succinate dehy-drogenase glucose-6-phosphate dehydrogenase and cholinedehydrogenase Heme forms covalent bonds with the globinprotein to form hemoglobin which is the major oxygencarrying pigment in RBCs of mammalians It takes part ina myriad of metabolic cycles such as in the energy producingreactions (the cytochromes of the Krebs cycle) in all the cellsand activates the energy producing oxidizing enzymes Apartfrom participation inmaintaining innumerable physiologicaland metabolic processes it is also necessary for DNA RNAcollagen antibody synthesis and so forth [52]The biologicalroles of iron in the human body are beyond the scope of thispaper and only few important ones have been listed

332 Role in Oral Health and Diseases The roles of iron inoral health and diseases are summarized as follows

(1) Iron deficiency anemia is the most commonmanifes-tation of low serum levels of this important trace ele-ment Microcytic hypochromic RBCs fatigue achlo-rhydria atrophy of epithelium loss of attention irri-tability dyspnea and lowered memory are some ofthe features of iron deficiency anemia [25] The oralmanifestations of iron deficiency anemia can be sum-marized as angular cheilitis atrophic glossitis gen-eralised oral mucosal atrophy candidal infectionspallor and stomatitis Plummer-Vinson syndrome orPaterson-Kelly syndrome or sideropenic dysphagia isa rare condition characterized by iron deficiency ane-mia dysphagia and koilonychia with women beingaffected more than men Dysphagia results fromthe presence of abnormal esophageal webs whichhave predisposition towards malignant transforma-tion [53]

(2) Oral premalignant lesions and conditions a signif-icant decrease in serum iron concentrations withelevated total iron-binding capacity has been foundin OSMF patientsThe decreased iron levels in OSMFpatients might be due to utilization of iron in collagensynthesis In addition deficient iron in the oraltissues results in decreased vascularity which furtherfacilitates percolation of arecoline (byproduct of arecanut) Further damage is caused by increased arecolinepercolation which enhances fibroblastic proliferationand collagen formation [25] Though majority of theliterature suggests that OSMF leads to iron deficiencydue to impaired dietary habits Bhattacharya et alreported an interesting case where iron deficiencyanemia primarily resulted in development of oral sub-mucous fibrosis whichwas successfully treated by oraladministration of iron supplements and antioxidants[54] Similarly low serum levels of iron have beenassessed in patients suffering from oral leukoplakia

(3) It has also been noted that serum ferritin levels areelevated and serum iron concentrations are decreasedwith tumor progression in head and neck carcinomasand thus heme can be used as a follow-up tool forpatients along with nutritional assessment [47]

34 Cobalt The presence of cobalt in animal tissues was firstestablished by Bertrand and Macheboeuf in 1925 which waslater confirmed by various researches using spectrographicmethods [55 56] Cobalt is an essential trace element for thehuman body and can occur in organic and inorganic formsIn organic form it forms an integral part of vitamin B12and has a substantial role in the formation of amino acidsand neurotransmitters Inorganic forms of cobalt are toxicto the human body and the longer they stay in the bodythe more the detrimental effects they cause in cells Cobaltions are absorbed within the human body through severalpathways firstly with food secondly by the respiratorysystem thirdly by the skin and finally as a component ofbiomaterials The cobalt ions enter the body through any ofthe abovementioned routes and bind with proteins within thebloodstream and get transported with blood to be depositedin tissues and cells The total body content of cobalt has beenestimated between 80 and 300mcg of vitamin B12 [57ndash59]

341 Biological Functions Vitamin B12 also known as cobal-amin is a water soluble vitamin and contains the biochemi-cally rare element cobalt in the center of a planar tetrapyrrolecorrin ring Vitamin B12 is produced as hydroxocobalaminwithin bacteria and conversion to methylcobalamin and51015840-deoxyadenosylcobalamin enzymatically active cofactorforms occurs within the body Cyanocobalamin the fourthvitamer of vitamin B12 can be metabolized in the body toan active coenzyme form and used in food supplementsErythropoietin essential for formation of erythrocytes stim-ulation is performed by vitamin B12 containing cobalt saltsand thus the deficiency of cobalt is strongly related todisturbances in vitamin B12 synthesis resulting in anemia andhypofunction of thyroidwith increased risk of developmentalabnormalities and failure in infants [59] Apart from being animportant constituent of these various forms of vitamin B12the presence of cobalt is necessary for the efficient formationof amino acids and various proteins for myelin sheathgeneration Cobalt also plays a decisive role in generatingneurotransmitters which are requisite for proper operationof an organism On the other hand excess of cobalt ionswithin the bodymight increase the action of thyroid and bonemarrow resulting in overproduction of erythrocytes fibrosisin lungs and asthma [60]

342 Role in Oral Health The roles of cobalt in oral healthare summarized as follows

(1) Cobalt part of vitaminB12 also referred to as extrinsicfactor is essential for formation of erythrocytesThus the most well-known manifestation of cobaltdeficiency in oral cavity is pernicious anemia whichis characterized by glossitis burning sensation beefyred tongue present in the form of patches or com-pletely red tonguewhich is also referred to asHuntersrsquoor Moellerrsquos glossitis and rarely shallow ulcers [61]

(2) Apart from erythropoiesis vitamin B12 also playsa significant role in nerve repair and regenerationHence deficiency of cobalt can have adverse effectssuch as peripheral neuropathy

Scientifica 7

(3) Lichen planus and oral lichenoid reactions have beenlinked to their exposure to Cr Co Ni and amalgamalloys that are released from metal alloys commonlyused in dentistry in the oral cavity These tracemetals when released from themetal alloys come intodirect contact with oral mucosa leading to immunemediated damage of basal epithelial keratinocytesand subsequently inducing sensitivity reactions in theform of OLR Some studies have linkedOLR to risk ofmalignant transformation [62]

35 Chromium The word ldquochromerdquo is a Greek word whichmeans ldquocolorrdquo Chromiumexists in divalent [Cr(II)] trivalent[Cr(III)] and hexavalent [Cr(VI)] oxidation states withCr(VI) and Cr(III) being the most stable forms amongwhich Cr(III) and Cr(VI) are insoluble and soluble formsrespectively The total body content of chromium is relativelylow and is about 0006 g in an average healthy human adultTrivalent Cr is an essential trace element and plays animportant role in glucosemetabolism by serving as a cofactorfor insulin action Hexavalent chromium is a toxic industrialpollutant and has been classified as carcinogen possessingmutagenic and teratogenic properties Chromium exposurethrough occupation via inhalation has been associated withvarious lung GIT and central nervous system cancersChromium is excreted principally in the urine and faeces andin small quantities in the hair sweat and bile [63]

351 Biological Functions Chromium is an important traceelement for overweight people as it is one of the key min-erals in controlling blood sugar and lipid levels Chromium[Cr(III)] increases the efficacy of insulin and stimulatingglucose uptake from the muscles and other tissues being themain ingredient of glucose tolerance factor (GFT) In caseof low serum levels of chromium the circulating level of(GFT) is also less and consequently insulin is less effective inreducing blood sugar As a result high blood sugar stimulatesfurther release of ineffective insulin [64 65] Chromium isthought to repress p53 a tumor suppressor protein whoseinactivation throughmutations is associated withmany typesof human cancers Chrome ulcers corrosive reactions onthe nasal septum acute irritation dermatitis and allergiceczematous dermatitis have been reported among individualsexposed to hexavalent chromium compounds Industrialworkers exposed to chromates have been documented to beat excessive risk of lung cancer

As chromium is present in very low amounts in the bodyit is difficult to ascertain the deficient state It is believed thatif concentrations of chromium are lower than the normalvalue of 014ndash015 ngmL in serum this will indicate thepresence of a severe chromium deficiency In spite of thatelevated plasma levels can coexist with a negative tissuebalance Hyperglycemia may be concomitant with raisedplasma chromium and increased urinary excretion Theconcentrations of chromium in urine hair and body fluidscould not reflect the true chromium status of the body [65]

352 Role inOral Health andDiseases Therole of chromiumin OLR has been discussed earlier [62] Hyperglycemic statusof diabetic patients in undiagnosed chromium deficient statemay lead to a wide spectrum of oral manifestations notedin diabetics such as delayed wound healing suppurativeperiodontitis various oral fungal infections premature peri-odontal diseases and hyposalivation [66]

36 Selenium Selenium is a vital trace element which is animportant component of the antioxidant enzymes such asglutathione peroxides and thioredoxin reductase [67] Theselenium salts required for various cellular functions insidethe humanbody are toxic in excess amountsMicroorganismsreportedly have several selenium containing enzymes andit is most likely that selenoproteins other than glutathioneperoxidase remain to be discovered in higher animalsHistorically endemic in children aged 2ndash10 years and inwomen of childbearing age Keshan disease had a geographicdistribution alongwide belt-like region throughoutmainlandChina from northeast to southwest Typical manifestationswere fatigue after even mild exercise cardiac arrhythmiaand palpitations loss of appetite cardiac insufficiency car-diomegaly and congestive heart failure The disease wasprevalent among people under selenium deficient diet andthe patients improved rapidly on fortification Similarlyselenium-responsive bone and joint disease Kashin-Beckdisease has also been detected in children aged 5ndash13 years inChina and less so in southeast Siberia Kashin-Beck diseasealso occurs in areas with low levels of selenium in cultivationsoil

361 Biological Functions Selenium is known to possessimmunomodulating and antiproliferative properties andmay effect immune response by altering the expression ofcytokines and their receptors or making immune cells moreresistant to oxidative stress [68 69] As a part of enzymeglutathione peroxidase along with vitamin E catalase andsuperoxide dismutase selenium forms component of one ofthe imperative antioxidant defence systems of the bodyThereis also compelling evidence that an unknown selenoenzymeprotein has some role in the synthesis of the triiodothyroninehormone from thyroxine [70 71]

362 Role in Oral Health and Diseases The serum levels ofselenium showed progressive reduction fromhealthy subjectsto patients having premalignant lesions like oral leukoplakiaand further decrease in patients suffering from oral cancerThere was a reduction in the selenium containing glutathioneperoxidase levels aswell and therewas a concomitant increasein the oxidative stress in the same order [72]

Hence it is clearly evident that decrease in the concen-trations of selenium will result in increased oxidative stressinside the body tissues with inadvertent harmful effectsThus nutritional supplementation with trace elements suchas selenium is an important rationale in the treatment ofpremalignant lesions like leukoplakia conditions as OSMFand oral cancer patients to reduce oxidative stress inside thebody [54]

8 Scientifica

A recent study evaluated the anti-inflammatory andantioxidant effect of selenium by administration in patientssuffering from oral mucositis secondary to high dosechemotherapy The researchers maintained that adequatesupplementation of selenium could produce cytoprotectiveeffects and antiulcer activity and concluded that selenium caneffectively reduce the duration and severity of oral mucositisin these patients [73]

37 Molybdenum Molybdenum minerals have been knownthroughout history but the element was discovered by CarlWilhelm Scheele in 1778 and first isolated in 1781 by PeterJacob Hjelm

371 Biological Functions Molybdenum as a componentof molybdoprotein takes part in the formation of activesites for various enzymes The three principal molybdenum-containing enzymes are xanthine dehydrogenaseoxidasealdehyde oxidase and sulphite oxidase A molybdenum-containing enzyme has some role to play in purinecatabolism It also influences protein synthesis and growthof the body [74] Molybdenum has an antagonistic effectagainst copper thus high concentrations of molybdenumcan reduce copper absorption and subsequently lead tocopper deficiency [75]

372 Role in Oral Health and Diseases Boron vanadiumand molybdenum are believed to possess a cariostatic effectVarious researches from Hungary and New Zealand stronglysuggested molybdenum-flouride interaction to have a strongcariostatic effect However the cariostatic effect of molyb-denum has been critically reviewed in the literature withinconclusive results Nonetheless teeth enamel accrues con-siderable amounts of molybdenum Further researches orinvestigations are warranted to derive reliable observations[76]

38 Fluorine Fluorine makes negligible part of body weightand enters the system principally through drinking water andto a lesser extent through foods

381 Biological Functions Fluorine in the form of fluorap-atite crystals is an important part of the organized matrixof hard tissues like bone and teeth It is also believed thatfluoride in combinationwith calcium stimulates osteoblasticactivity [64]

382 Role in Oral Health and Diseases Low levels of fluoridein drinking water have been associated with dental decayThe excessive concentrations of fluoride during calcificationstage of the teeth can result in a kind of enamel hypoplasiatermed dental fluorosis Clinically dental fluorosis can varyfrom small white opacities in the enamel to severemottling ofthe tooth structure with increasing severityThe overall effectof excessive fluoride intake on the dental structure dependsonmany factors such as concentration of fluoride in drinkingwater stage of calcification of teeth when exposure occurredduration of exposure and amount of exposure [61]

39 Iodine Iodine is a vital trace element required at all stagesof life especially during formative years It is important tosustain the daily functions of human body and deficiency orexcess can have significant adverse effects on the body

391 Biological Functions Iodine is an essential componentof thyroid hormones that is tetraiodothyronine (T4 orthyroxine) and triiodothyronine (T3) It plays a significantrole in the functioning of the parathyroid glands Iodineplays an important role in general growth and developmentof the body along with maintaining metabolic processes[64]

392 Role in Oral Health and Diseases There can be innu-merable symptoms of iodine deficiency or excess The defi-ciency of iodine is more commonly evident Most commonlyreported symptoms of iodine deficiency are extreme fatigueirritability mental disturbances weight gain facial puffinessconstipation and lethargy Untreated infants have the risk ofdeveloping cretinism and end up suffering from poor growthand mental retardation [64]

It has also been hypothesized that dietary deficiency orexcess of iodine plays an imperative role in oral mucosa andin salivary glands physiology Salivary glands can protecttheir own cells fromperoxidation due to iodine concentratingability through sodium iodide symporter and peroxidaseactivity Iodide seems to have a primitive antioxidant functionin iodide concentrating organisms Significant role of iodinein oral immune defense mechanism may be substantiated byhigh concentration of iodine in thymus S Venturi and MVenturi also suggested that these actions of iodides might beimportant for prevention of various oral and salivary glandsdiseases [77]

It was also evident in a study conducted by Littleton andFrohlich in 1993 that the skeletal remains from iodine richzones of the world showed greater attrition lesser dentalcaries and reduced premature teeth loss Early loss of teethcan be a primary factor in undernutrition and loss of healthand compromised quality of life [78]

Deficiency of iodine is not uncommon in various parts ofthe world population Worldwide fortification of edible salthas been undertaken to offset the iodine deficiency Hypothy-roidism is characterized by decreased levels of thyroid hor-mone With respect to oral involvement there can be evidentthickening of lips due to deposition of glycosaminoglycans inthe subcutaneous tissues Similarly macroglossia of tonguecan be seen because of the same reason If children areaffected there may be delayed eruption of teeth without anyinfluence on teeth formation [53]

Hyperthyroidism in adults can result in diffuse brownpigmentation of the gingiva buccal mucosa palate andtongue similar to Addisonrsquos disease The mechanism throughwhich the stimulation of melanin synthesis occurs is yetunclear but pigmentation tends to resolve with the treatmentof thyroid abnormality [79]

Scientifica 9

4 Detection of Trace Elements andAssessment of Nutritional Status

This was done as follows

(1) Though various methods have been employed todetermine the presence of trace elements it is a cum-bersome and nonfruitful job due to their wide distri-bution within the living tissues and enzyme systemsColorimetric and spectrographic methods are usedcommonly to analyse the amount of trace elementsTypically spectroscopy and electrochemical methodsare preferred for solitary element analysis whereasneutron activation analysis and spectroscopic meth-ods are used for determination of more than oneelement [11]

(2) The most easily determined deficiency is of ironwhich can be determined by performing laboratorytests [80] Bone marrow smear containing no stain-able iron is definitive Elevated total iron-bindingcapacity low serum iron level and a low serumferritin concentration are considered diagnostic foriron deficiency Recently newer approaches like ery-throcyte zinc porphyrin assay have also been used inprimary screening tests for assessing iron status [81]

(3) The reported optimal plasma or serum ratio betweencopper and zinc is 070ndash100 Diagnosing zinc defi-ciency is a persistent challenge as mentioned beforein the paper Plasma or serum zinc levels are the mostcommonly used indices for evaluating zinc deficiencySevere Cu deficiency can be found by testing for lowplasma or serum copper levels low ceruloplasminand low superoxide dismutase levels but these are notvery sensitive tests and fail to determine marginalcopper deficiency [16 82]

(4) The assessment of the iodine nutritional status of apopulation or group living in an area or region sus-pected to be iodine-deficient area can be performedby assessment of the goitre rate measurement ofurinary iodine excretion and determination of thelevel of blood T3 T4 or TSH

(5) Tissue chromium stores apparently do not trulyreflect the blood chromium thus serum chromiumconcentration is not a good indicator of chromiumstatus It has been postulated that serum chromiumlevels lower than 014ndash015 ngmL indicate the pres-ence of a severe chromium deficiency Excessiveexposure of individual to chromium via occupationor accident may be reflected by elevated serumchromium

(6) Different tissues such as blood hair and nails havebeen analysed for determining the nutritional statusof selenium Generally these tissues can provide asound appraisal of selenium status if dietary seleniumintake is relatively uniform

(7) Tissue levels status of other trace elements in normalindividuals is difficult to determine

Table 2 Trace elements and preventive medicine [5]

Prevention Trace element involvedPredisposition to anemia Iron cobalt copperReduction in antioxidantpotential

Zinc iron manganeseselenium copper

Promotion of aging and itscause

Zinc copper seleniumchromium

Immunodeficiency Zinc iron copper seleniumIncreased carcinogenicity Zinc copper selenium

Promoted atherosclerosis Zinc selenium iron copperchromium

Increased incidence ofdiabetes mellitus Chromium zinc selenium

Predisposition to tastedisorder Zinc

Predisposition to dental caries Fluorine molybdenumPredisposition to goiter Iodine

5 Conclusion

It is one of the most difficult tasks to diagnose trace elementdeficiencies nutritionally as well as clinically The deficientintake of an essential trace element may diminish significantbiological functions within tissues and restoration of physi-ological levels of that element relieves the impaired functionor prevents impairment The human body has an elaboratesystem for managing and regulating the amount of key tracemetals circulating in blood and stored in cells The abnormallevels of these trace elementsmay developwhen the body failsto function properly or there are improper levels in dietarysourcesThere are convincing lines of evidence that a diet richin antioxidants and essential minerals is indispensable for ahealthy mind and body Preventive medicine in the recentyears has gained more attention than anything else as quotedaptly ldquoprevention is better than curerdquo Selective reproductionof association between preventivemedicine and various traceelements has been presented in Table 2 [5] Oral and generalhealth cannot be viewed independently and as amatter of factthe oral cavity can mirror the systemic health effectively Thecombination of various micronutrients and trace elementshas been used as a treatment strategy for oral diseases like oralleukoplakia oral submucous fibrosis oral cancer and so forthas their collective outcome is more beneficial as compared tosolitary application Hence knowledge of the clinical aspectsof trace elements is becoming requisite for general as well asoral physicians

Competing Interests

The authors declare that they have no competing interests

References

[1] I L Chapple G R Brock M R Milward N Ling and J BMatthews ldquoCompromised GCF total antioxidant capacity inperiodontitis cause or effectrdquo Journal of Clinical Periodontol-ogy vol 34 no 2 pp 103ndash110 2007

10 Scientifica

[2] C O Enwonwu R S Phillips and W A Falkler Jr ldquoNutritionand oral infectious diseases state of the sciencerdquo Compendiumof Continuing Education in Dentistry vol 23 no 5 pp 431ndash4482002

[3] P J Moynihan ldquoThe role of diet and nutrition in the etiologyand prevention of oral diseasesrdquo Bulletin of the World HealthOrganization vol 83 no 9 pp 694ndash699 2005

[4] M Chen R M Andersen D E Barmes M H Leclerqand S V Little Comparing Oral Health Systems A SecondInternational Collaborative Study World Health OrganizationGeneva Switzerland 1997

[5] OWada ldquoWhat are trace elementsTheir deficiency and excessstatesrdquo JapanMedical Association Journal vol 47 no 8 pp 351ndash358 2004

[6] WHO Trace-Elements in Human Nutrition Report of a WHOExpert Committee WHO Technical Report Series No 532World Health Organization Geneva Switzerland 1973

[7] E Frieden ldquoNew perspectives on the essential trace elementsrdquoJournal of Chemical Education vol 62 no 11 pp 915ndash923 1985

[8] E Frieden ldquoThe evolution of metals as essential elements [withspecial reference to iron and copper]rdquo in Protein-Metal Inter-actions M Friedman Ed vol 48 of Advances in ExperimentalMedicine and Biology pp 1ndash31 Springer New York NY USA1974

[9] M S Willis S A Monaghan M L Miller et al ldquoZinc-inducedcopper deficiency a report of three cases initially recognizedon bone marrow examinationrdquo American Journal of ClinicalPathology vol 123 no 1 pp 125ndash131 2005

[10] J Osredkar and N Sustar ldquoCopper and zinc biological roleand significance of copperzinc imbalancerdquo Journal of ClinicalToxicology 2011

[11] C Minoia E Sabbioni P Apostoli et al ldquoTrace elementreference values in tissues from inhabitants of the Europeancommunity I A study of 46 elements in urine blood and serumof Italian subjectsrdquo Science of the Total Environment vol 95 pp89ndash105 1990

[12] S J Adelstein andB LVallee ldquoCoppermetabolism inmanrdquoTheNew England Journal of Medicine vol 265 pp 892ndash897 1961

[13] E D Harris ldquoCopper homeostasis the role of cellular trans-portersrdquo Nutrition Reviews vol 59 no 9 pp 281ndash285 2001

[14] J L Groff S S Gropper and S M Hunt Advanced Nutritionand HumanMetabolism West Publishing Company New YorkNY USA 1995

[15] S J Lippard and JM BergPrinciples of Bioinorganic ChemistryUniversity Science Books Mill Valley Calif USA 1994

[16] M Araya F Pizarro M Olivares M Arredondo M Gonzalezand M Mendez ldquoUnderstanding copper homeostasis inhumans and copper effects on healthrdquo Biological Research vol39 no 1 pp 183ndash187 2006

[17] M Bonham J M OrsquoConnor B M Hannigan and J J StrainldquoThe immune system as a physiological indicator of marginalcopper statusrdquo British Journal of Nutrition vol 87 no 5 pp393ndash403 2002

[18] D Rakel Integrative Medicine Saunders Elsevier 2nd edition2007

[19] C D Davis ldquoLow dietary copper increases fecal free radicalproduction fecal water alkaline phosphatase activity and cyto-toxicity in healthy menrdquo Journal of Nutrition vol 133 no 2 pp522ndash527 2003

[20] Y Christen ldquoOxidative stress and Alzheimer diseaserdquo TheAmerican Journal of Clinical Nutrition vol 71 no 2 pp 621sndash629s 2000

[21] D L Watts ldquoThe nutritional relationships of copperrdquo Journal ofOrthomolecular Medicine vol 4 no 2 pp 99ndash108 1989

[22] B L Odell Biochemical Basis of the Clinical Effects of CopperDeficiency Alan R Liss Inc New York NY USA 1982

[23] W Harless E Crowell and J Abraham ldquoAnemia and neu-tropenia associated with copper deficiency of unclear etiologyrdquoAmerican Journal of Hematology vol 81 no 7 pp 546ndash5492006

[24] C R Trivedy K A A S Warnakulasuriya T J Peters RSenkus V KHazarey andNW Johnson ldquoRaised tissue copperlevels in oral submucous fibrosisrdquo Journal of Oral Pathology andMedicine vol 29 no 6 pp 241ndash248 2000

[25] VDDesaiMV S Kumar R J Bathi I Gaurav andR SharmaldquoMolecular analysis of trace elements in oral submucous fibrosisand future perspectivesrdquo Universal Research Journal of Den-tistry vol 4 no 1 pp 26ndash35 2014

[26] P Rajalalitha ldquoMolecular pathogenesis of OSMFrdquo Journal ofOral Pathology and Medicine vol 34 no 6 pp 321ndash328 2005

[27] L Prashanth K K Kattapagari R T Chitturi V R Baddamand L K Prasad ldquoA review on role of essential trace elements inhealth and diseaserdquo Journal of NTRUniversity ofHealth Sciencesvol 4 pp 75ndash85 2015

[28] R A Wapnir Protein Nutrition and Mineral Absorption CRCPress Boca Raton Fla USA 1990

[29] C C Pfeiffer and E R Braverman ldquoZinc the brain andbehaviorrdquo Biological Psychiatry vol 17 no 4 pp 513ndash532 1982

[30] M R Broadley P JWhite J P Hammond I Zelko and A LuxldquoZinc in plantsrdquo New Phytologist vol 173 no 4 pp 677ndash7022007

[31] E N Whitney and S R Rolfes Understanding NutritionThomson Learning Boston Mass USA 10th edition 2010

[32] M Valko H Morris andM T D Cronin ldquoMetals toxicity andoxidative stressrdquoCurrentMedicinal Chemistry vol 12 no 10 pp1161ndash1208 2005

[33] H H Sandstead ldquoUnderstanding zinc recent observations andinterpretationsrdquo Journal of Laboratory and Clinical Medicinevol 124 no 3 pp 322ndash327 1994

[34] T J McCarthy J J Zeelie and D J Krause ldquoThe antimicrobialaction of zinc ionantioxidant combinationsrdquo Journal of ClinicalPharmacy andTherapeutics vol 17 no 1 pp 51ndash54 1992

[35] N W Solomons ldquoMild human zinc deficiency produces animbalance between cell-mediated and humoral immunityrdquoNutrition Reviews vol 56 no 1 pp 27ndash28 1998

[36] A S Prasad ldquoZinc an overviewrdquoNutrition vol 11 no 1 pp 93ndash99 1995

[37] C A Heyneman ldquoZinc deficiency and taste disordersrdquo Annalsof Pharmacotherapy vol 30 no 2 pp 186ndash187 1996

[38] A S Prasad F W J Beck S M Grabowski J Kaplan and RH Mathog ldquoZinc deficiency changes in cytokine productionandT-cell subpopulations in patientswith head andneck cancerand in noncancer subjectsrdquo Proceedings of the Association ofAmerican Physicians vol 109 no 1 pp 68ndash77 1997

[39] K Simmer and R P Thompson ldquoZinc in the fetus andnewbornrdquo Acta Paediatrica Scandinavica Supplement vol 319pp 158ndash163 1985

[40] N Fabris and E Mocchegiani ldquoZinc human diseases andagingrdquo Aging Clinical and Experimental Research vol 7 no 2pp 77ndash93 1995

[41] WMaret andHH Sandstead ldquoZinc requirements and the risksand benefits of zinc supplementationrdquo Journal of Trace Elementsin Medicine and Biology vol 20 no 1 pp 3ndash18 2006

Scientifica 11

[42] Institute of Medicine and Food and Nutrition Board DietaryReference Intakes for Vitamin A Vitamin K Arsenic BoronChromium Copper Iodine Iron Manganese MolybdenumNickel Silicon Vanadium and Zinc National Academy PressWashington DC USA 2001

[43] P E Milbury and A C Richer Understanding the AntioxidantControversy Scrutinizing the ldquoFountain of Youthrdquo GreenwoodPublishing Group 2008

[44] R J Lynch ldquoZinc in the mouth its interactions with dentalenamel and possible effects on caries a review of the literaturerdquoInternational Dental Journal vol 61 supplement 3 pp 46ndash541984

[45] R I Henkin ldquoZinc in taste functionrdquo Biological Trace ElementResearch vol 6 no 3 pp 263ndash280 1984

[46] M Das and R Das ldquoNeed of education and awareness towardszinc supplementation a reviewrdquo International Journal of Nutri-tion and Metabolism vol 4 no 3 pp 45ndash50 2012

[47] A Jayadeep K Raveendran Pillai S Kannan et al ldquoSerumlevels of copper zinc iron and ceruplasmin in oral leukoplakiaand squamous cell carcinomardquo Journal of Experimental ampClinical Cancer Research vol 16 no 3 pp 295ndash300 1997

[48] J G Ray R Ghosh D Mallick et al ldquoCorrelation of traceelemental profiles in blood samples of Indian patients withleukoplakia and oral submucous fibrosisrdquo Biological TraceElement Research vol 144 no 1ndash3 pp 295ndash305 2011

[49] S J Mulware ldquoTrace elements and carcinogenicity a subject inreviewrdquo 3 Biotech vol 3 no 2 pp 85ndash96 2013

[50] D M Vasudevan and S Sreekumari Text Book of BiochemistryforMedical Students JaypeeNewDelhi India 5th edition 2007

[51] E Frieden ldquoThe chemical elements of liferdquo Scientific Americanvol 227 no 1 pp 52ndash60 1972

[52] U Satyanarayana andU Chakrapani Essentials of BiochemistryBook and Allied Kolkata India 2nd edition 2008

[53] B D Neville D D Damm C M Allen and J E BouquotOral and Maxillofacial Pathology Elsevier Chennai India 3rdedition 2009

[54] P T Bhattacharya T Khaitan S B Sarkar and R Sinha ldquoOralsubmucous fibrosis secondary to iron deficiency anemia acase report etiopathogenesis and managementrdquoThe Journal ofNutrition Health and Aging vol 20 no 2 pp 205ndash208 2016

[55] D G Barceloux ldquoCobaltrdquo Journal of ToxicologymdashClinical Toxi-cology vol 37 no 2 pp 201ndash216 1999

[56] N Yamagata S Murata and T Torii ldquoThe cobalt content ofhuman bodyrdquo Journal of Radiation Research vol 3 no 1 pp4ndash8 1962

[57] N A Taylor and T S Marks ldquoFood and nutrition boardrecommended daily allowancesrdquo Journal of Human Nutritionand Dietetics vol 32 pp 165ndash177 1974

[58] J M Christensen O M Poulsen and M Thomsen ldquoA short-term cross-over study on oral administration of soluble andinsoluble cobalt compounds sex differences in biological lev-elsrdquo International Archives of Occupational and EnvironmentalHealth vol 65 no 4 pp 233ndash240 1993

[59] K Czarnek S Terpiłowska and A K Siwicki ldquoSelected aspectsof the action of cobalt ions in the human bodyrdquo CentralEuropean Journal of Immunology vol 40 no 2 pp 236ndash2422015

[60] N Lombaert D Lison P Van Hummelen and M Kirsch-Volders ldquoIn vitro expression of hard metal dust (WC-Co)mdashresponsive genes in human peripheral blood mononucleatedcellsrdquo Toxicology and Applied Pharmacology vol 227 no 2 pp299ndash312 2008

[61] W G Shafer M K Hine and B M Levy A Textbook of OralPathology Elsevier India Chennai India 4th edition 2004

[62] S B Ismail S K S Kumar and R B Zain ldquoOral lichenplanus and lichenoid reactions etiopathogenesis diagnosismanagement and malignant transformationrdquo Journal of OralScience vol 49 no 2 pp 89ndash106 2007

[63] Z Krejpcio ldquoEssentiality of chromium for human nutrition andhealthrdquoPolish Journal of Environmental Studies vol 10 no 6 pp399ndash404 2001

[64] WorldHealthOrganizationTrace Elements inHumanNutritionand Health World Health Organization Geneva Switzerland1996

[65] J M Nguta Essential Trace Elements Trace Elements inHuman and Animal Health LAP Lambert Academic Publish-ing Saarbrucken Germany 2010

[66] N Kulkarni K Kalele M Kulkarni and R Kathariya ldquoTraceelements in oral health and disease an updated reviewrdquo Journalof Dental Research and Review vol 1 no 2 pp 100ndash104 2014

[67] M P Rayman ldquoSelenium and human healthrdquo The Lancet vol379 no 9822 pp 1256ndash1268 2012

[68] A B Serwin W Wasowicz J Gromadzinska and B Cho-dynicka ldquoSelenium status in psoriasis and its relations to theduration and severity of the diseaserdquo Nutrition vol 19 no 4pp 301ndash304 2003

[69] H W Kuo S F Chen C C Wu D R Chen and J H LeeldquoSerum and tissue trace elements in patients with breast cancerin Taiwanrdquo Biological Trace Element Research vol 89 no 1 pp1ndash11 2002

[70] J R Arthur andG R Beckett ldquoSeleniumdeficiency and thyroidhormone metabolismrdquo in Selenium in Biology and Medicine AWendell Ed pp 90ndash95 Springer Berlin Germany 1989

[71] B Contempre J E Dumont B Ngo C H Thilly A TDiplock and J Vanderpas ldquoEffect of selenium supplementationin hypothyroid subjects of an iodine and selenium deficientarea the possible danger of indiscriminate supplementationof iodine-deficient subjects with seleniumrdquo Journal of ClinicalEndocrinology and Metabolism vol 73 no 1 pp 213ndash215 1991

[72] N Swain and J G Ray ldquoAltered trace element level and antiox-idant activity in whole blood of oral leukoplakia and cancerpatients in comparison with healthy controlsrdquo InternationalJournal of Oral amp Maxillofacial Pathology vol 2 no 2 pp 2ndash6 2011

[73] Z Jahangard-Rafsanjani K Gholami M Hadjibabaie et alldquoThe efficacy of selenium in prevention of oral mucositis inpatients undergoing hematopoietic SCT a randomized clinicaltrialrdquo Bone Marrow Transplantation vol 48 no 6 pp 832ndash8362013

[74] M P Coughlan ldquoThe role of molybdenum in human biologyrdquoJournal of Inherited Metabolic Disease vol 6 supplement 1 pp70ndash77 1983

[75] N F Suttle ldquoRecent studies of the copper-molybdenum antag-onismrdquo Proceedings of the Nutrition Society vol 33 no 3 pp299ndash305 1974

[76] M Curzon J Kubota and B Bibby ldquoEnvironmental effects ofmolybdenum on cariesrdquo Journal of Dental Research vol 50 no1 pp 74ndash77 1971

[77] S Venturi and M Venturi ldquoIodine in evolution of salivaryglands and in oral healthrdquo Nutrition and Health vol 20 no 2pp 119ndash134 2009

[78] J Littleton and B Frohlich ldquoFish-eaters and farmers dentalpathology in the Arabian Gulfrdquo American Journal of PhysicalAnthropology vol 92 no 4 pp 427ndash447 1993

12 Scientifica

[79] M S Greenberg M Glick and J A Ship Burketrsquos OralMedicine CBS Publisher New Delhi India 11th edition 2008

[80] C Brugnara ldquoIron deficiency and erythropoiesis new diagnos-tic approachesrdquoClinical Chemistry vol 49 no 10 pp 1573ndash15782003

[81] R F Labbe and A Dewanji ldquoIron assessment tests transferrinreceptor vis-a-vis zinc protoporphyrinrdquo Clinical Biochemistryvol 37 no 3 pp 165ndash174 2004

[82] L Goldman and D Ausiello Cecil Medicine Saunders ElsevierPhiladelphia Pa USA 23rd edition 2007

[83] K Park Parkrsquos Textbook of Preventive and Social MedicineBanarsidas Bhanot Jabalpur India 21st edition 2011

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

2 Scientifica

21 WHO Classification 1973 [6] As per this classificationnineteen trace elements have been divided into three groups

(1) Essential elements zinc (Zn) copper (Cu) selenium(Se) chromium (Cr) cobalt (Co) iodine (I) man-ganese (Mn) and molybdenum (Mo)

(2) Probably essential elements(3) Potentially toxic elements

22 Friedenrsquos Classification of Elements In 1981 Frieden pro-posed a biological classification of trace elements based ontheir amount in tissues [7]

(1) Essential trace elements boron cobalt copperiodine iron manganese molybdenum and zinc

(2) Probably essential trace elements chromium fluo-rine nickel selenium and vanadium

(3) Physically promotive trace elements bromine lith-ium silicon tin and titanium

23 Friedenrsquos Categorical Classification of Elements [8]Twenty-nine types of elements present in the human bodyhave been classified into five major groups as follows

(i) Group I basic components of macromolecules suchas carbohydrates proteins and lipids Examplesinclude carbon hydrogen oxygen and nitrogen

(ii) Group II nutritionally important minerals alsoreferred to as principal or macroelements The dailyrequirement of these macroelements for an adult per-son is above 100mgday Examples include sodiumpotassium chloride calcium phosphorous magne-sium and sulfur

(iii) Group III essential trace elementsThe trace elementsare also called minor elements An element is con-sidered a trace element when its requirement per dayis below 100mg The deficiency of these elements israre but may prove fatal Examples include copperiron zinc chromium cobalt iodine molybdenumand selenium

(iv) Group IV additional trace elements Their role isyet unclear and they may be essential Examplesinclude cadmium nickel silica tin vanadium andaluminumThis group may be equivalent to probablyessential trace elements in the WHO classification

(v) Group V these metals are not essential and theirfunctions are not known They may produce toxicityin excess amounts Examples include gold mercuryand lead This group is equivalent to potentially toxicelements defined in the WHO classification

3 Discussion

An extensive and complex system is functioning inside thehuman body tomanage andmaintain the amount of essentialtrace elements within a normal range Micronutrients from

diet are transported into the blood if there is deficiencyenter cells if cellular levels are not adequate or are excretedif blood and cell levels are satisfactory or elevated Variousessential trace elements along with nutritional requirementand dietary sources have been listed in Table 1

31 Copper Copper is the thirdmost abundant trace elementwith only 75ndash100mg of total amount in the human body[9] Copper is present in almost every tissue of the bodyand is stored chiefly in the liver along with the brain heartkidney and muscles [10] Copper is absorbed in the gut andtransported to the liver In human blood copper is principallydistributed between the erythrocytes and in the plasma [11]It is transported in the form of ceruloplasmin into the plasmawhere its metabolism is controlled and is excreted in bile [12]Ceruloplasmin accounts for 90 of the copper content inblood and is responsible for carrying copper to the deficientcells [13] Copper-zinc metalloenzyme superoxide dismutasecontains 60of the copper in erythrocytes and the remaining40 is loosely bound to other proteins and amino acids

311 Biological Functions A significant number ofmetabolicenzymes function properly due to copper [13ndash16]The biolog-ical functions of copper have been listed [14ndash16]

(1) The enzyme cytochrome c oxidase comprising cop-per and iron plays a vital role in energy productionduring aerobic respiration

(2) Copper is also present in superoxide dismutase whichdetoxifies superoxides by converting them to oxygenand hydrogen peroxide

(3) Copper is also a component of lysyl oxidase whichtakes part in the synthesis of collagen and elastinCopper is also essential for maintaining the strengthof the skin hair blood vessels and epithelial andconnective tissue throughout the body

(4) Cu plays a considerable role in the production ofhemoglobin Ceruloplasmin catalyzes the oxidationof iron which subsequently is necessary to bind to itstransport protein transferrin [12]

(5) Melanin production copper containing enzymetyrosinase converts tyrosine to melanin

(6) Myelin production Cu is also necessary for thesynthesis of phospholipids found inmyelin sheaths inperipheral nerves [13 16]

(7) Copper is also required for the production of thethyroid hormone thyroxine [13]

(8) Copper can act as both an antioxidant and a prooxi-dant As an antioxidant Cu scavenges or neutralizesfree radicals and may reduce or help prevent someof the damage they cause [16ndash19] Copper promotesfree radical damage to the tissues when it acts asprooxidant [20]

312 Role in Oral Health and Diseases The symptoms ofcopper deficiency are hypochromic anemia neutropenia

Scientifica 3




Copper 2000 120583g




Iron 18mg




Zinc 15mg




Cobalt 6120583g


Not known









4 Scientifica

Table 1 Continued



Selenium 70120583g




Iodine 150120583g
















Scientifica 5















6 Scientifica











Scientifica 7










8 Scientifica















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Scientifica 3




Copper 2000 120583g




Iron 18mg




Zinc 15mg




Cobalt 6120583g


Not known









4 Scientifica

Table 1 Continued



Selenium 70120583g




Iodine 150120583g
















Scientifica 5















6 Scientifica











Scientifica 7










8 Scientifica















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















4 Scientifica

Table 1 Continued



Selenium 70120583g




Iodine 150120583g
















Scientifica 5















6 Scientifica











Scientifica 7










8 Scientifica















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Scientifica 5















6 Scientifica











Scientifica 7










8 Scientifica















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















6 Scientifica











Scientifica 7










8 Scientifica















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Scientifica 7










8 Scientifica















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















8 Scientifica















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Scientifica 9




















5 Conclusion


Competing Interests


References


10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















10 Scientifica









































Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Scientifica 11






































12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















12 Scientifica











of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















review article nutritional aspects of essential trace elements in...

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