Trace Elements and Human Health

 

Trace Elements and Human Health

PKGhatak, MD

The elements making a human body are of three categories. Elements that are plentiful like carbon, oxygen, nitrogen, hydrogen, etc. These elements form covalent bonds and make up the tissue; the less plentiful elements are sodium. chloride, potassium, etc. which are responsible for maintaining osmotic pressure gradient between cellular and extracellular fluid and finally elements that are rare like zinc, copper, chromium, cobalt, selenium, magnesium, and molybdenum. These trace elements are bio-active substances or parts of many enzymes system responsible for various functions of the body.

In addition, elements found in human tissues are not parts of normal tissue or serve any useful purpose but accumulate in the body due to persistent exposure and often are harmful to the body, for example - lead, arsenic, mercury, etc.

Trace elements and their functions.

The trace elements have similar dietary sources, digestion, absorption and transport system. The elements differ mainly by the enzyme they form, even then many enzyme systems containing the trace elements participate in sequence on the same substrate or metabolic process. This is particularly true with copper, zinc and manganese.

There are more than one standard daily requirement numbers - usual daily intake, recommended daily allowance, no adverse effects on a minimum dose, adverse effects on a dose and then various ratios. This also added confusion about the amount safe to take and should be good for the body.

Selenium.

Selenoproteins and selenium containing proteins are required for DNA synthesis, also needed for thyroid hormone production and metabolism. Selenium provides protection against infection.

Selenium exists in two forms: inorganic and organic forms. Most selenium in human tissues is incorporated non-specifically with the amino acid methionine. Skeletal muscle is the major site of selenium storage. Both selenocysteine and selenite are reduced to generate hydrogen selenide, which in turn is converted to selenophosphate for selenoprotein biosynthesis. Selenium is active as an anticancer agent; it prevents ischemic heart disease and selenium has vitamin E like effects on the body.

Daily requirement. 55 to 70 micrograms. Selenium containing food are Brazilian nuts, seafood, animal organs, cereals, shellfish and dairy products.

Chromium.

Chromium in nature exists as trivalent and hexavalent forms. Chromium is a part of glucose transport protein. For organic processes, trivalent form is required and chromium is present in the enzyme system involved in the catabolism of fatty acids and carbohydrates. It is also required for the synthesis of cholesterol. It is also considered an antioxidant. Excess chromium is considered a risk factor for carcinoma of the lung, and premature atherosclerosis. Chromium poisoning produces GI upset, peptic ulcers, liver and kidney dysfunction and growth retardation in children. It is required for parenteral nutrition. The daily dietary requirement is 35 micrograms for adults.

Manganese.

It is one of the trace element constituents of superoxide dismutase, required for mitochondrial functions and integrity of the cell membrane. It is needed for carbohydrate, cholesterol and protein metabolism, sex hormone production and growth in children. Like many other trace elements, it is required for brain cell development, connective tissue, bones & joints and blood clotting.

Manganese is absorbed in the small intestine through an active transport system and, possibly by diffusion when oral intakes are high. After absorption, some manganese remains free, but most are bound to transferrin, albumin, and plasma protein alpha-2-macroglobulin. Manganese is taken up by the liver and other tissues. The daily requirement 2 to 2.5 mg for adult males, women need lesser amounts. In poisoning from excess exposure in welding, alloy industries and agriculture. Excess manganese in the body may produce neurological symptoms including Parkinson's disease. In iron deficiency anemia and liver cirrhosis, the adverse effects of Manganese develop more readily.  Leafy green vegetables, green tea, and whole grains are good dietary sources of chromium.

Molybdenum.

Molybdenum is required for processing DNA and other proteins. Molybdenum is a structural constituent of a cofactor and is required for the function of four enzymes- sulfite oxidase, xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime reducing component (mARC). These enzymes metabolize sulfur-containing amino acids and heterocyclic compounds including purines and pyrimidines. Xanthine oxidase, aldehyde oxidase, and mARC are involved in metabolizing drugs and toxins.

The kidneys are responsible for Molybdenum excretion. Molybdenum, in the form of molybdopterin, is stored in the liver, kidney, adrenal glands, and bones. Molybdenum deficiency is rare.

Serum levels of molybdenum range from 0.28 ng/mL to 1.17 ng/mL. Daily requirement – 45 to 50 micrograms.
Legumes are the richest sources of molybdenum. Other foods high in molybdenum include whole grains, nuts, and beef liver.

Cobalt.

Cobalt lies in the center of the vitamin B12 molecule. The role of B12 in humans is well known and discussed in an earlier blog (see vitamin B12 blog). Besides its role in RBC, cobalt is required for nerve cell formation, as a neurotransmitter, and for nerve impulse conduction. Food is the main source of cobalt but it can be absorbed through the skin from prolonged contact and by inhalation of contaminated air. Surgical implants containing cobalt can leach and can produce toxicity, produce chronic inflammation from increased production of IL-1 and IL-6 and TNF alpha from the macrophages.

Toxicity to cobalt results from depression of cellular respiration because of the downregulation of the cytochrome P-450 enzyme. Other enzymes like catalase and aminolaevulinic synthetase involved in tissue respiration are also depressed by cobalt toxicity. Depresses Kreb cycle enzymes decrease energy and metabolism. Cobalt can replace zinc in enzymes like alcohol dehydrogenase and can increase alcohol toxicity. In toxic levels, cobalt interferes with Iodine and may result in thyroid goiter.

Copper.

Enzymes containing copper cuperoenzymes have various functions in the body.  Cuperoenzymes are needed in brain development, immune functions, angiogenesis, skin pigment production. Iron absorption and incorporation of iron into RBC is copper dependent. Copper is an important oxidase enzyme system. Ceruloplasmin, hephaestin and zyklopen are important among them. The iron transport protein - Ferroprotein, depends on these enzymes for a steady supply. Cytochrome C oxidase, required for so many cellular functions is a copper-containing enzyme system. Copper, zinc superoxide dismutase (CuZnSOD), is an antioxidant enzyme. K562 cells, a human erythroleukemic cell line, can extract copper from ceruloplasmin and incorporate it into CuZnSOD.

Only a small amount of copper is present in the body and mainly present in the skeleton and skeletal muscles. The daily requirement of copper for adults is about 900 micrograms. The main dietary sources of copper are seafood, animal organs, nuts, beans and chocolate. A small amount of copper enters food during cooking in copper wares and vinegar, wine added during cooking accelerates copper leaching into food and may cause poisoning. Excess flux used in copper plumbing in the previous generation is another source of copper poisoning. Acute copper poisoning and suicide attempts using copper sulfate are common occurrences. Excess copper is harmful to the body. Copper produces liver disease - acute hepatitis and liver necrosis after ingestion of a large amount. Chronic copper poisoning is seen in an inherited autosomal recessive disease - Wilson disease from accumulated copper in the liver producing liver cirrhosis, copper deposits on the cornea and other tissues containing ceruloplasmin. An x-link recessive inherited disease - Menkes disease, (a similar inherited defect like Hemophilia A), is due to the ATP7A gene. Mutated genes produce defects in copper transport leaving excess copper in the small intestine and renal tubules and at the same time deficiency of copper in hair, skeleton, blood vessels structural abnormalities and nerve cell suffer from deficiency. 

Zinc. 

Zinc is involved in numerous aspects of cellular metabolism. Zinc is part of approximately 100 enzymes and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division, lymphocyte proliferation response to mitogen Immune defects produce abnormal binding of nuclear factor kb and decrease in DNA, decreased production IL-2(interleukin2) and killer T-Cells. Zn acts as an antioxidant. Zinc deficiency can impair macrophage and neutrophil functions, natural killer cell activity, and complement activity, and normal growth and development. Zinc is required for a proper sense of taste. Humans have no specialized zinc storage system.

The daily requirement of zinc is 9 to 12 mg, excess intake can interfere with copper absorption and anemia.

Zinc deficiency is usually common in India mostly in breast milk fed children.  Frequent infections, diarrhea and growth retardation and hypogonadism are presenting symptoms. Excess Zinc in the elderly is not a rare occurrence in these days of megavitamins and heavy dose of minerals intake. It appears that many elderlies believe - " if 1 microgram is good then 1 gm will be better." Excess Zinc interferes with iron and copper abortion and incorporation of iron in the RBC, and copper containing enzymes.  Zinc substitution of other trace elements in enzymes results in poor functioning immune system, and frequent infection.

The gene SLC39A4 defect, either acquired or inherited as autosomal recessive mode, results in lack of absorption of zinc from the small intestine. The disease is characterized by pustular dermatitis around the mouth and anus, diarrhea, nail dystrophy, and poor health. This condition is known as Acrodermatitis enteropathica.

The buzzword of this generation is Anti Oxidant. Nutritional supplements and various chemicals marketed as antioxidants are sought after substances. It is better to be prudent and a bit skeptical before ingesting chemicals that could poison the brain, liver and kidneys.

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