What are Trace Elements? - 日本医師会

1 JMAJ, August 2004 Vol. 47, No. 8351 This article is a revised English version of a paper originally published inthe Journal of the Japan Medical Association (Vol. 129, No. 5, 2003, pages 607 612).What are Trace Elements? The human body is composed of elementswhich can be roughly divided into abundantelements and Trace elements. Abundant ele-ments consist of the major elements that areinvolved in the formation of covalent bondsWhat are Trace Elements? Their deficiency and excess states JMAJ 47(8): 351 358, 2004 Osamu WADAP rofessor Emeritus, University of TokyoAbstract:Elements which are detected in small but not precisely known amountsin the living body were called Trace elements in the past.

2 Recent advances inanalytical technologies, such as the development of atomic absorption spectrom-etry, have made it possible to measure these elements precisely and to determinetheir functions and the characteristics of their deficiency and excess so-called vitamin boom has passed, and it now appears to be boom-time fortrace elements. Nowadays, cases with Trace element deficiencies are oftenencountered clinically, especially during high-calorie parenteral therapy or enteralnutrition, and congenital abnormalities of Trace element metabolism have beenclarified successively. Thus, knowledge of the clinical aspects of Trace elements isbecoming indispensable for front-line ) Meanwhile, epidemiologicalsurveys and animal studies have suggested the possibility that some Trace elementdeficiencies are associated with a reduced anti-oxidant potential in organisms(which is believed to possibly underlie the onset of cancer and atherosclerosis),accelerated aging, developmental retardation in children, and an increased inci-dence of abnormal pregnancies, immunological abnormalities, and lifestyle-relateddiseases.

3 Thus, from the viewpoint of prophylactic medicine, study, survey, andprophylaxis of Trace elements are also attracting close words: Trace element; Trace element deficiency; Excess of Trace elements;Congenital abnormality in Trace element metabolismand are important constituents of tissues(oxygen, carbon, hydrogen, nitrogen, etc.), andsemi-major elements, which often exist in theionic state, and are involved in functions of theliving body through maintenance of osmoticpressure and membrane potentials (potassium,sodium, etc.). Major elements account for 96% Trace Elements352 JMAJ, August 2004 Vol. 47, No. 8 Table 1 Functions of Trace Elements and Symptoms of Their Deficiency and Excess StatesTraceEnzymes containingelementthe elements andPhysiological functionsSymptoms of deficiency stateSymptoms of excess stateactive formsCarbonic anhydraseProtein metabolismMajor symptoms:Acute:PeptidaseLipid metabolismGradually exacerbatingRelative Fe-Cu deficiency,Alcohol dehydrogenaseCarbohydrate metabolismeruptions, first affectingnausea, vomiting,Alkaline phosphataseBone metabolismthe face and perineumabdominal pain, melena,PolymeraseAssociated symptoms.

4 Hyperamylasemia,Zinc fingerStomatitis, glossitis, alopecia,somnolence, hypotension, changes, abdominallung edema, diarrhea,symptoms (diarrhea, vomiting),jaundice, oliguriafeverChronic:Delayed wound healing, dwarfismReduced reproductiveGrowth retardation, negativefunction, dwarfism,N balance,taste disorder, hyposmia,Immunosuppression,anemiaMental symptoms (depression),Taste disorder, anorexiaCeruloplasminHemopoiesisAnemiaNa usea, vomiting,Monoamine oxidaseBone metabolismLeukopeniaheartburn, diarrhea,Cytochrome oxidaseConnective tissueNeutropeniajaundice, hemoglobinuria,Ascorbic acid oxidasemetabolismDisturbed maturation ofhematuria, oliguria,CopperDopamine -hydroxylasemyeloleukocytesanuria, hypotension, coma,Superoxide dismutaseBone changes (children)

5 Osseous age,irregular/spurring metaphysis,bone radiolucency,bone cortex thinningGlucose tolerance factorCarbohydrate metabolismAbnormal glucose toleranceNausea, vomiting,Cholesterol metabolismReduced respiratory quotientpeptic ulcer, CNS disorder,Connective tissueWeight lossLiver/kidney dysfunction,ChromiummetabolismPeripheral neuropathygrowth retardationProtein metabolismIncreased serum free fatty acidsAbnormal nitrogen balanceMetabolic consciousnessdisturbanceGlutathione peroxidaseAntioxidant actionMyalgia (lower extremities)Selenosis (alopecia, nail(GSH-Px)T4 T3 conversionCardiomyopathydetachment, CNS disorder)Selenium5 -deiodinase (type I)Reduced carcinogenicity(myocardial cell collapse,Various selenoproteinsactionfibrosis)Nail bed whiteningArginaseBone metabolismReduced serum cholesterolParkinsonian syndromePyruvate carboxylaseCarbohydrate metabolismReduced coagulationEarly chronic:Superoxide dismutaseLipid metabolismHair reddeningImpotence, loss of vigor,ManganeseGlycosyltransferaseReprod uctionDermatitis (miliaria crystallina)somnolence, anorexia,ImmunityGrowth retardationedema, myalgia, headache,Increased radiolucency at theexcitation, fatigueepiphyses of long bonesAdvanced stage.

6 Extrapyramidal disorderXanthine oxidaseAmino acid metabolismTachycardiaHyperuricemia, goutXanthine dehydrogenaseUric acid metabolismPolypneaAldehyde oxidaseSulfuric acid/sulfurousNight blindnessMolybdenumNitrous acid oxidaseacid metabolismScotomaIrritabilitySomnolenceD isorientationComaCobaltVitamin B12 HemopoiesisPernicious anemiaCobalt poisoningMethylmalonic acidemiaIodineThyroid hormoneTissue metabolismGoiter, hypothyroidismGoiter, hypothyroidism(Summary of many reports) , August 2004 Vol. 47, No. 8353of the total body weight, and the semi-majorelements account for 3 to 4% of the total bodyweight. Deficiency of major elements can leadto nutritional disorders, and their presence inexcess can cause obesity.

7 Deficiencies or excessstates of semi-major elements often result inwater and electrolyte Trace elements of the human bodyinclude zinc (Zn), copper (Cu), selenium (Se),chromium (Cr), cobalt (Co), iodine (I), manga-nese (Mn), and molybdenum (Mo). Althoughthese elements account for only of thetotal body weight, they play significant roles, , as active centers of enzymes or as tracebioactive substances. A major outcome of traceelement deficiencies is reduced activity of theconcerned enzymes. However, since each traceelement is related to so many enzymes, defi-ciency of a single Trace element is often notassociated with any specific clinical manifesta-tions, but rather manifests as a combination ofvarious symptoms.

8 Because of the presence oftrace elements in very small amounts and theabsence of specific clinical features associatedwith their deficiency, it is often difficult forclinicians to identify deficiencies of some par-ticular Trace 1 lists the enzymes containing traceelements, and summarizes the physiologicalfunctions of Trace elements and the character-istics of their deficiency and excess Elements as Nutrients orMedicines2)Like vitamins, Trace elements were alsooriginally viewed as nutrients. They are listed inthe Japanese recommended dietary allowance(RDA). Because of the tendency in recenttimes towards unbalanced food intake, exces-sive purification of crops, and dieting practicedwidely to reduce body weight, deficiency ofzinc (a Trace element abundantly contained inanimal foods and crops) are encountered rela-tively elements exert pharmacological actionsif they are ingested in amounts several to tentimes higher than the nutritional ingestion of Trace elements as medi-cines has also been reported, which may occa-sionally lead to poisoning.

9 To avoid such poison-ing, the RDA table displays also the referencedose (RfD, , the highest permissible dose) foreach element. However, the RfD shown in theRDA table is relevant as reference values onlywhen Trace elements are ingested as ordinarynutrients. Table 21) lists the pharmacologicallyeffective actions of Trace elements when theyare consumed in excess. However, when deal-ing with Trace elements, caution must be exer-cised to avoid excessive Intake, Recommended DietaryAllowance, Reference Dose, andSafety Margin of Trace Elements, andCauses of Deficiency StatesTable 32) summarizes these parameters inDEFICIENCY AND EXCESS OF Trace ELEMENTST able 2 Trace Elements and the Potential Effects ofReplenishment, Prophylaxis, andPharmacological EffectsTrace elementPotential effects of replenishment,prophylaxis.

10 And pharmacological effectsIronCorrection of latent iron deficiencyResistance to infectionsWound healingImproved resistance to infections andZincimmune functionsCorrection of developmental retardationand gonadal hypoplasiaCorrection of taste disorderChromiumCorrection of carbohydrate metabolismPrevention of atherosclerosisAnti-cancer activitySeleniumPrevention of ischemic heart diseaseVitamin E-like activityFluorinePrevention of dental cariesIodineCorrection of latent iodine deficient goiter(Quoted from Wada, O. et al.: Trace elements and theirabnormalities. Integrated Handbook of Internal Medicine 6,Nakayama-Shoten Co., Ltd., Tokyo, 1995; pp. 253 263.)354 JMAJ, August 2004 Vol.