Trace Elements

Trace Elements

Fundamentals

  • Trace elements are chemical elements required by the human body in very small amounts (typically less than 100 mg/day) yet they are essential for life.

  • They are also called micronutrients or oligoelements.

  • They participate in numerous biochemical and physiological processes, often as cofactors for enzymes, structural components of proteins, or regulators of gene expression.

  • They are minerals that make up 5% of our diet.

Physiological Roles of Trace ElementsCategories:

  • Catalytic: Many trace elements are integral to metalloenzymes that drive metabolic pathways (e.g., Zn in carbonic anhydrase, Cu in cytochrome c oxidase).

  • Structural: Stabilize biological molecules and cell structures (e.g., Zn fingers in transcription factors, F in hydroxyapatite of teeth).

  • Regulatory: Participate in hormone synthesis, redox signaling, and gene regulation (e.g., I in thyroxine, Se in selenoproteins).

Balance & Imbalance:

  • Deficiency (Hypo): May cause anemia (Fe), hypothyroidism (I), growth retardation (Zn), cardiomyopathy (Se).

  • Excess (Hyper): Often toxic due to accumulation (e.g., hemochromatosis from Fe overload, selenosis from Se excess).

  • Some trace elements can be toxic in non-physiologic forms or doses (e.g., Cr6+ is carcinogenic, while Cr3+ is essential).

Essential Trace Elements1. Iron (Fe)

  • Most essential trace element.

  • In the respiratory chain, iron functions as an electron carrier.

  • Iron is responsible for the transport of molecular oxygen in higher organisms.

  • Most of the iron found in the body is associated with two types of protein:

  • Hemoproteins

  • Iron storage and/or transport proteins

Iron Deficiency & Treatment:

  • Deficiency: Anemia; can also occur in patients being maintained on hemodialysis.

  • Treatment: 3 - 6 mg of elemental iron/kg/day.

  • An iron compound used for replacement or supplemental therapy must meet two requirements:

  1. Be biologically available

  2. Be non-irritating

  • Official Oral preparations of iron:

  • Ferrous sulfate

  • Ferrous fumarate

  • Ferrous gluconate

  • Adverse effects: Epigastric pain, nausea, vomiting, gastritis, metallic taste, constipation or diarrhea.

  • Liquid prep: Staining of teeth.

2. Zinc (Zn)

  • Second most abundant trace element.

  • Cofactor for: DNA polymerase, alkaline phosphatase, carboxypeptidase.

  • Regulates: Growth, immune system, collagen synthesis, wound healing, bone metabolism, reproduction, taste, smell & vision.

Medicinal and Pharmaceutical Uses:

  • Reduces the duration of diarrhea.

  • High doses of zinc prevent dysmenorrhea.

  • Required in producing testosterone.

  • Treatment of common cold.

  • Treatment of warts.

Zinc Deficiency:

  • In children: Growth retardation & skeletal abnormalities.

  • In adults: Impaired smell & taste, decreased appetite, skin lesions, and hair loss.

3. Copper (Cu)

  • 3rd most important trace element.

  • Diet rich in copper: Red meat, shellfish, water pumped through copper pipes.

  • Body content of copper is 80 - 120 mg.

  • Transported through metalloenzymes: 90% bound to ceruloplasmin, 9% to albumin, and 1% is free.

Body Functions:

  • Hemoglobin formation: Despite an adequate supply of iron, copper is required to prevent anemic conditions.

  • Three postulated roles for copper in hemoglobin synthesis:

  1. Facilitate iron absorption.

  2. Stimulatory to the enzymes in the heme and/or globin biosynthetic pathways.

  3. Involved in the mobilization of stored iron, preparative to the incorporation of iron into the hemoglobin molecule.

  • Other roles:

  • Important in oxidative phosphorylation.

  • Associated with the formation of aortic elastin.

  • Component of tyrosinase, an enzyme responsible for the conversion of tyrosine to the black pigment, melanin.

Copper Imbalances:

  • Copper Deficiency: Fragile hair, depigmented skin, myeloneuropathy, anemia.

  • Copper Overaccumulation:

  • Wilson's Disease: Autosomal recessive disorder caused by mutation in the ATP7b gene resulting in excessive accumulation of Cu.

  • Clinical features: Diarrhea, vomiting, cardiac & renal failure, hepatic necrosis, encephalopathy.

4. Chromium (Cr)

  • In 1957, extracted from pork kidney and named "glucose tolerance factor" as it corrected hyperglycemia.

  • Chromium supplementation has been shown to improve or normalize impaired glucose tolerance in some diabetics, elderly people, and malnourished children.

  • Regulates plasma lipoprotein concentration and reduces cholesterol and triglycerides.

5. Manganese (Mn)

  • Essential for normal growth and development.

  • Encompasses a broad class of enzymes with manganese cofactors: oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, lectins, and integrins.

  • The reverse transcriptases of many retroviruses (though not lentiviruses such as HIV) contain manganese.

6. Sulfur (S)

  • Integral to amino acids methionine and cysteine, which are building blocks of proteins.

  • Found in vitamins thiamine (B1) and biotin.

  • Forms disulfide bonds in protein structures; stabilizes tertiary and quaternary structures (e.g., insulin, antibodies).

  • Widely distributed as:

  • Sulfhydryl groups of cysteine

  • Disulfide linkages in protein from cysteine

  • Sulfate salts and esters found in mucopolysaccharides and sulfolipids

  • Involved in liver detoxification via glutathione and phase II conjugation.

  • Component of cartilage and connective tissue (chondroitin sulfate).

Sulfur Imbalances:

  • Deficiency (Hypo): Rare because sulfur needs are met if protein intake is adequate. Possible in severe protein-energy malnutrition or restrictive diets lacking methionine and cysteine.

  • Symptoms: Poor growth and wound healing, weak hair/nails, fatigue, impaired detoxification capacity.

  • Excess (Hyper): Usually from high exposure to sulfur dioxide gas or sulfite preservatives.

  • Symptoms: Respiratory irritation, asthma exacerbation in sensitive individuals, GI upset with large oral doses of sulfates. Chronic excessive intake of certain sulfur-containing amino acids may contribute to acid load and bone demineralization.

7. Iodine (Iodide / I)

  • An essential ion necessary for the synthesis of two hormones produced by the thyroid gland: triiodothyronine (T3) and thyroxine (T4).

  • Iodine Deficiency:

  • Results in enlargement of the thyroid gland, known as simple or colloid goiter (characterized by swelling at the neck).

  • The enlargement is a compensatory mechanism where the body attempts to make up for hormone deficiency by increasing the size of the gland.

8. Selenium (Se)

  • Least abundant trace element.

  • May be of therapeutic value in the treatment of kwashiorkor (a protein deficiency affecting large numbers of children).

  • Functions:

  • Component of Glutathione peroxidase (GTH-Px): plays an important role in immune system function and a crucial role in controlling oxygen metabolism.

  • Deficiency: Low selenium leads to Keshan's disease (a type of cardiac myopathy discovered in China where soil selenium was absent).

9. Molybdenum (Mo)

  • Acts as a catalytic center in metalloenzymes that facilitate oxidation-reduction reactions.

  • Involved in:

  • Purine catabolism: Xanthine oxidase (purine metabolism to uric acid).

  • Sulfur metabolism: Sulfite oxidase (detoxification of sulfites).

  • Detoxification pathways: Aldehyde oxidase (drug metabolism).

10. Cobalt (Co)

  • Present in Vitamin B12 (cyanocobalamin, hydroxocobalamin).

  • Used in treating pernicious anemia and Vitamin B12 deficiency neuropathies.

  • Cobalt as part of Vitamin B12 is required for:

  • DNA synthesis

  • Erythropoiesis

  • Neurologic function (myelin maintenance)

  • Vitamin B12-dependent enzymes:

  • Methionine synthase (methylation reactions)

  • Methylmalonyl-CoA mutase (fatty acid & amino acid metabolism)

Non-Essential Trace Elements1. Bromine (Bromide / Br)

  • Introduced for its antiepileptic effect to produce a beneficial depression of convulsions associated with epilepsy.

  • Potassium bromide may still be useful for grand mal seizures in children for whom other drugs prove unsuitable.

  • Previously utilized in certain cases of sleeplessness.

  • Toxicity (Bromism): Early signs include insomnia, restlessness, dizziness, weakness, and headache.

  • Elimination: Tends to be hastened by the administration of sodium chloride; ammonium chloride may be used when sodium intake must be limited.

2. Lithium (Li)

  • Central nervous system depressant.

  • Preparations like lithium carbonate and lithium citrate are valuable in treating hypomanic and manic states.

  • Lithium salts should be discontinued if a satisfactory response is not obtained in 14 days.

  • Has a diuretic action and can induce a diabetes insipidus condition by interfering with vasopressin action.

  • Toxicity: Aggravated by a reduction in sodium intake. Intoxication is treated by withholding the lithium salt and providing adequate sodium intake.

3. Gold (Au)

  • Discovered as gold cyanide to be effective in vitro against tubercle bacillus, marking the beginning of modern gold therapy.

  • Chrysotherapy: Used primarily in the treatment of rheumatoid arthritis (based on an early belief that the disease was an atypical form of tuberculosis).

  • Administered on a weekly basis because it remains bound to albumin for several days.

  • Also used in non-disseminated lupus erythematosus.

  • Toxicity: Involves the skin, joints, blood, kidney, and liver.

  • Toxicity Treatment: Can be managed by cessation of gold administration and supportive treatment; dimercaprol can be used to remove accumulated gold in severe cases.

4. Arsenic (As)

  • As potassium arsenite, previously used in the treatment of trypanosomiasis.

  • As 1% arsenic trioxide solution, used for leukemia because it lowers leukocyte count.

5. Antimony (Sb)

  • Differs from arsenicals by being less readily absorbed and by producing topical irritation because it is more caustic than arsenicals.

  • As antimony potassium tartrate (tartar emetic) and antimony sodium tartrate, previously used as a treatment for schistosomiasis.