CHAPTER THREE

Essential, Trace, and Nonessential Ions

Overview

Essential ions are needed by the body for normal and adequate functioning. They have specialized biochemical
functions. Trace ions are needed in minute quantities but are also important for physiological functioning. Nonessential
ions are generally not needed for body functions but some may have beneficial pharmacological action in appropriate
dosage. Some of these may even have toxicological action in levels found in the environment. Deficiency syndromes are
common for essential and trace ions most of which can be remedied through food supplementation or through
medication in more severe cases.

Essential and Trace Ions

Iron (Fe2+)

Most iron found in the body is of two types:

a. Hemoprotein; This is responsible for respiration and for carrying oxygen. Cytochrome c is an example of a
respiratory enzyme whose iron is complexed in a porphyrin (heme) ring system. Iron is in the form of either ferrous
or ferric. Catalase and peroxidae are oxidative enzymes also containing iron. The other types are myoglobin and
hemoglobin which store and/or transport oxygen. Patients with iron-deficiency anemia have a decreased capability
of transporting oxygen.

b. Iron Storage and/or Transport Proteins. Ferritin and hemosiderin are iron storage proteins in the liver, spleen,
and bone marrow. Iron storage proteins are biological reserves of iron for utilization. The iron in ferritin is stored in
the ferric form but is incorporated and released in the ferrous form. Transferrin is the major iron transport protein
of the blood plasma. It carries iron across biological membranes.

Diet is the primary source of iron; however,supplementation may be necessary due to the low percentage
absorption of iron from food. Most iron absorption takes place in the duodenum whee contents are still acidic; thus
during iron supplementation; ascorbic acid is given concomitantly.

Recommended Dietary Allowance (RDA) males - 8 mg/d; Females 18 mg/d

Food sources: Iron can be found in liver, kidney, shellfish, muscle meats, poultry, heart, egg yolk, dried legumes,
cane molasses, and nuts in average to high quantities while low in milk and refined sugar.
Functions: Iron is an essential component of several important metalloproteins such as hemoglobin, myoglobin,
and many oxidation-reduction enzymes.
Deficiency Syndromes: Hypochromic microcytic anemia is the characteristic end result of iron deficiency.
Depending on severity the anemia is accompanied by listlessness (quality of state of lacking physical strength or
vigor) and tiredness, palpitation on exertion, sore tongue, angular stomatitis ( inflammation of the corners of
the mouth), dysphagia ( difficulty in swallowing), and kilonychia (spoon nails, a disease that indicates
hyperchromic anemia in iron- deficiency anemia).
Toxicity: Moderate excess above RDA is considered harmless in normal patients. However, individuals with
 Essential, Trace, and Nonessential Ions

metabolic defects such as those whose iron absorption is not carefully controlled and even those who have
normal iron intake may develop hemochromatosis resulting from excess tissue accumulation.
Iron-Deficiency Anemia

OFFICIAL IRON COMPOUNDS :

1. Ferrous fumarate USP38/NF33
Brand Name: Ferrovit, Fergesol
Content: 33% of elemental iron
2. Ferrous gluconate USP38/NF33
Brand Name: Fergon
Content: approximately 12% of elemental iron
3. Ferrous sulfate USP38/NF33
Brand names: United Home ferrous sulfate, Feosol, Ferglobin
Content : 20% of elemental iron
4. Iron Dextran Injection USP38/NF33
Brand name: Dexferrum
Description: It is a sterile, colloidal solution of ferric hydroxide in complex with
partially hydrolyzed dextran of low molecular weight, in water, for injection.
5. Iron sorbitex Injection USP38/NF33
Description: It is a sterile solution of a complex of iron, sorbitol, and citric acid
that is stabilized with the aid of dextrin and an excess of sorbitol.
NOTE: Calculation of dosage for iron preparations should always be based on the
amount of elemental iron to be administered.

Copper (Cu+,Cu 2+)

Copper may be Stored in the liver, incorporated in ceruloplasmin, or excreted in bile. Copper deficiency can lead to a
lack of iron available to the newly-forming red blood cell.
Other uses/importance of copper:
1. Oxidative phosphorylation (ATP production by cellular respiration). Copper is a constituent of cytochrome
oxidase, the terminal oxidase in the electron transport mechanism from which high-energy phosphate bonds
are derived.
2. Formation of aortic elastin. It may be that copper is needed for amine oxidase activity and may play a role in
the formation of cross linkages of elastin.
3. Component of tyrosinase

Recommended Dietary Allowance (RDA): 900 ug/d

Food Sources: Copper can be found in liver, kidney, shellfish, nuts, dry legumes, whole-grain cereals in average
to high quantities but low in milk, muscle meat, eggs, fruit, and Vegetable.
Functions: Copper functions in the absorption and utilization of iron, electron transport, connective tissue metabolism,
phospholipid formation, purine metabolism, and the development of the nervous system.
Deficiency Syndromes: The most common defect observed in copper-deficiency is anemia. Other abnormalities
Include growth depression, skeletal defects, demyelination and degeneration of the nervous system, ataxia, defects in
pigmentation and structure of hair or wool, reproductive failure, and cardiovascular lesions, including dissecting
aneurysms.
Toxicity: a genetic disease in humans, leads to excess copper accumulation in the brain, liver, and kidney, resulting in
mental and neurological abnormalities. Penicillamine is the drug of choice to remove excess copper from the body.

Zinc (Zn2+)
Recommended Dietary Allowance (RDA): Males - 11 mg/d; Females - 8 mg/d

Food Sources: Zinc can be found in meat, egg yolk, whole-grain cereals, oysters, fowl, milk, fruits, fish, and
vegetables in average to high quantities.
Functions: Zinc occurs in many vital metalloproteins such as carbonic anhydrase, carboxypeptidases A and B,
alcohol dehydrogenase, glutamic dehydrogenase, D-glyceraldehyde-3-phosphate dehydrogenase, lactic
dehydrogenase, malic dehydrogenase, alkaline phosphate, aldolase and many more. It is also required for the
growth of every animal species is involved in the regulation of gene expression; in the secretion of insulin, and in
the function of the hormone. Zinc is known to play a central role in the immune system experience increased
susceptibility to a variety of pathogens. It is likewise important for the normal development and functions of cells
mediating nonspecific immunity as neutrophils and killer cells. Moreover, it has a profound effect on key
immunologic mediators as zinc has a role in basic cellular functions such as DNA replication, RNA transcription, cell
division, and cell activation.
Deficiency Syndromes: Impaired synthesis of nucleic acids and proteins has been observed in inc deficiency. Other
characteristics of deficiency include skin lesions, alopecia, abnormal feathering in birds, deformed and poorly
mineralized bones, hyperkeratinization of esophagus, reduced numbers of circulating lymphocytes, impaired
reproduction in males and females, fetal abnormalities, and decreased learning ability.
Toxicity : Acute toxicity of zinc is characterized by dehydration, electrolytic imbalance, stomach pain, lethargy,
dizziness, muscular incoordination, and renal failure. High zinc intakes are known to lower copper absorption.
 Essential, Trace, and Nonessential Ions

Iodine (I1-)

Iodine is an essential ion needed for the synthesis of the two hormones;- triiodothyronine (T3) and
thyroxine (T4), both of which are produced by the thyroid gland. The other role of iodine is its pharmacological
action as a fibrinolytic agent, expectorant, and bactericidal agent.

Recommended Dietary Allowance (RDA): 150ug/d

Food Sources: Iodine can be found in salt water fish, shellfish, iodized salt, and milk in average to high quantities.
Function: The only known function of iodine is to produce the thyroid hormones to regulate cellular oxidation;
Deficiency Syndromes: The iodine deficiency disease is goiter. Among the young, iodine deficiency results in
depressed growth, delayed sexual development, rough skin, and thin hair. In severe deficiency; cretinism, feeble-
mindedness, and deaf-mutism occur. Among adults, reproductive failure in female and decreased fertility in male
can set in.
Toxicity: Iodism may develop in individuals with too much intake of iodine, characterized by pain in the salivary
glands, watery eyes, and exacerbation of acne.

Official Iodine Products :

1. Iodine USP38/NF33
2. Iodine Topical Solution USP38/NF33 a skin antiseptic.
3. Strong iodine solution USP38/NF33, along with antithyroid medicines prepares the thyroid gland for surgical
removal and treats certain overactive thyroid conditions (hyperthyroidism, thyroid storm) by shrinking the size of
the thyroid gland and by decreasing the amount of thyroid hormones the body makes. It may also protect the
thyroid gland after radioactive iodine treatment.
4. lodine tinctures USP38/NF33, an antiseptic.
5. Strong iodine tincture USP38/NF33 is an antiseptic and disinfectant applied on superficial cuts, abrasions, insect
bites, and minor bruises.
6. Povidone iodine USP38/NF33 is an antiseptic to prevent or treat infections in wounds including ulcers, burns,
cuts, minor surgical procedures and other minor injuries.
7. Potassium iodide USP38/NF33 is an expectorant to liquefy thick and tenacious sputum in several lung conditions.
Moreover, it is an adjunctive treatment in cystic fibrosis, in chronic sinusitis, and after surgery, in the prevention of
atelectasis (collapse of the expanded lung); and in hyperthyroidism in adjunction with an antithyroid drug and in
nuclear radiation emergency. Off-label uses include acute febrile neutrophilic dermatosis and lymphocutaneous
sporotrichosis.

Chromium (Cr2+, Cr3+ )

Recommended Dietary Allowance (RDA): Males- 35 ug/d; Females - 25 ug/d

Food Sources: Chromium can be found in dried brewer's yeast, bran and germs of cereal grains,
molasses,liver, refined cereals, and refined sugar in average to high quantities.
Functions: Chromium has been designated a glucose tolerance factor; A variety of biochemical studies
attests to the required presence of insulin for all functions of chromium.
Deficiency Syndromes: The principal defect in chromium deficiency is an impairment of glucose utilization
downstream from the insulin receptor; furthermore, disturbances in protein and lipid metabolism have also
 been observed.
Toxicity: Toxicity is caused by hexavalent compounds but little toxic effect is attributed to trivalent chromium.
After contact, inhalation, or ingestion of the former, the lethal effects are: dermatitis, allergic and eczematous
skin reactions, skin and mucous membrane ulcerations, perforation of the nasal septum, allergic asthmatic
reactions, bronchial carcinomas, gastro-enteritis, hepatocellular deficiency, and renal oligo anuric deficiency.
Other reported cases associated with avoiding chromium toxicity are prevention of occupational risks,
biological monitoring of workers, and treatment of poisoning.

Manganese (Mn2+)

Recommended Dietary Allowance (RDA): Male- 2.3 mg/d; females - 1.8 mg/d
Food Sources: Manganese can be found in whole-grain cereals, dried legumes, tubers, fruits, non leafy
vegetables, fruits, root and stem vegetables, muscle meats, and milk in average to high quantities
Function: Manganese is a co-factor in the synthesis of mucopolysaccharideS of cartilage and in the
conversion of mevalonic acid to squalene.
Deficiency Syndromes: Glucose utilization is impaired in manganese deficiency. Characteristics of this
deficiency include' growth depression, skeletal abnormalities (ranging from mild rarefaction to crippling
deformities), mortality of the young, perosis (slipping of the Achilles tendon and accompanying joint
deformity) in birds, and depressed reproduction of both males and females.
Toxicity: Miners exposed to manganese dioxide dust for long periods of time develop psychiatric
abnormalities that resembles schizophrenia. This is followed by crippling neurological disorders similar to
those found in Parkinson's disease. Excessive manganese intake can lead to chronic manganism whose
symptoms include mental disturbances, progressive bradykinesia (abnormal slowness of movement),
asthenia (weakness), paresis (incomplete paralysis), dysarthria (imperfect articulation in speech), dystonia
(disordered muscle tone), and disturbances in gait.

Molybdenum (M04+ M06+)

Recommended Dietary Allowance (RDA): RDA:45ug/d)

Food Sources: Molybdenum can be found in liver, kidney, dried legumes, whole-grain cereals, leafy
vegetables, fruits, root and stem vegetables, muscle meats, and milk in average to high quantities.
Function: It is an important constituent imoxidase and aldehyde oxidases.
Deficiency Syndromes: Molybdenum cofactor deficiency (MOCOD) is a rare autosomal recessive metabolic
disorder characterized by onset in infancy of poor feeding, intractable seizures, and severe psychomotor
retardation. Characteristic biochemical abnormalities include decreased serum uric acid and increased urine
sulfite levels due to the combined enzymatic deficiency of xanthine dehydrogenase and sulfite oxidase, both
of which use molybdenum as a cofactor. Most affected individuals die in early childhood (summary by Reiss
2000; Reiss et al. 2011).
Toxicity: Toxicity in humans is not likely to occur;

Selenium (Se2-)
Recommended Dietary Allowance (RDA): 55 ug/d
Food Sources: Selenium can be found in liver and kidney.
 Essential, Trace, and Nonessential Ions

Functions: Selenium is an component of several -enzymes including glutathione peroxidase. It provides a link
between the antioxidant properties of vitamin E and the biological function of selenium in preventing most of the
same selenium deficiency problems,
Deficiency Syndromes: Deficiency of selenium can lead to the following abnormalities: growth depression,
muscular dystrophy, degeneration of myocardium, neurological lesions, liver necrosis, pancreatic fibrosis,
exudative disathesis, ceroid-pigment deposition in adipose tissue, and death.
Toxicity: Acute Selenium toxicity is characterized by abdominal pain, excess salivation, grating of teeth, paralysis,
and blindness. Eventually, disturbed respiration leads to death.

Nonessential Ions

Fluoride (F-1)
Compound:Sodium fluoride (NaF) USP38/NF33
Use: an anticariogenic to prevent osteoporosis in the elderly
Deficiency syndrome: Tooth decay is the resultant defect.
Toxicity: fluorosis, the mottling of teeth

Bromide (Brl)
Compound: The unofficial compounds are Sodium Bromide (NaBr), Poyassium Bromide (KBr) and Ammonium
Bromide ( NH4Br)
Use : It is a CNS depressant as a sedative and an anti-epileptic treatment.
Toxicity : Bromism characterized by insomia, restlessness, dizziness, and weakness.

Lithium (Li+)
Compound: Lithium Carbonate (Li2C03) USP38/NF33
Use: Mood stabilizer in manic-depressive psychosis with diuretic action
Toxicity: affects the kidneys and induces diabetes insipidus, evident in patients with low salt intake.

Gold (Au+)
Compounds: Göld sodium thiomalate USP 28, aurothioglucose USP 28
Uses: A cure for rheumatoid arthritis and non-disseminated -lupus erythematosus
Contraindication: These are contraindicated in patients with a kidney disease, a history of infectious hepatitis,
skin or blood disorders, diabetes, pregnancy, hypertension, or congestive heart failure.

Arsenic (Ar3+, Ar5+)

Compound: potassium arsenite (Fowler's Solution) USP38/NF33
Uses: a rat poison component and a protoplasmic poison for trypanosamiasis and amoebiasis; also a treatment
for leukemia
Toxicity: The symptoms of toxicity in humans include headaches, confusion, severe diarrhea, drowsiness and the
development of leukonychia (white spots) in the fingernails, also known as Mees' lines.
Antimony (Sb3+, Sb5+)
Compounds: Antimony potassium tartrate (Kb2 Sb2 ( C4H2O6)2) USP38/NF33, organic antimony
Uses: an expectorant in cough preparations and a medication for schistosomiasis.

Aluminum (AP+)
Compound :soluble salt like alum, chlorine, and sulfate, insoluble salt like phosphate, hydroxide.
Uses: an astringent; deodorant and a carbonate as non-systemic antacids

Silver (Ag+)
Compounds:Toughened silver nitrate (AgN03) USP38/NF33
Uses: a styptic and in silver protein preparations, an antiseptic; likewise, an,antimicrobial.
Toxicity : leads to Argyria; a discoloration of the skin.

Barium (Ba2+)
Compound: Barium sulfite (BaS04) USP38/NF33
Use: a radiopaque agent in X-ray

Cadmium (Cd2+)
Compound : Cadium sulfide (CdS) and Cadium sulfate (CdS04)
Uses: an anti-dandruff ingredient and an astringent
Toxicity: Drinking water contaminated with cadmium results in itai - itai, a disease.

Lead (Pb2+, Pb4+)

Compounds: Lead chloride (PbCl2), Lead acetate(Pb ( CH3COO)2) USP38/NF33 and lead oxide (PbO) constitute a
Goulard's extract, also referred to as subacetate of lead.
Use: an astringent}
Toxicity: Plumbism sets in, a cumulative poisoning inhibiting heme synthesis. The most serious toxic form is lead
encephalopathy which affects the brain and has a high fatality rate. Chronic lead nephropathy is common in heavy
moonshine drinkers.

Mercury (Hg22+, Hg2+)

Compounds: Mercurous chloride (Hg2Cl2), ammoniate mercury (HgNH2Cl), yelloy mercuric oxide (HgO)
Uses: a diuretic, a germicide, and an antiseptic
Toxicity: Hydrargyria an acute poisoning, is brought about by ingestion of soluble mercuric salt and chronic
poisoning from industry and contaminated food. Symptoms of toxicity include tremors, emotional changes,
insomnia, neuromuscular changes, headaches, disturbances in sensations, changes in nerve responses, and a
decline in cognitive function.

Nickel (Ni2+, Ni4+)

Compounds: Nickel bromide (NiBr2), nickel carbonate (NiC03), and (nickel sulfate (NiS04)
Uses: a cure for epilepsy and for certain parasitic-skin diseases; also a tonic
Toxicity: Causes contact dermatitis or "nickel's itch"
 Strontium (Sr2+)

Compounds: Strontium bromide (SrBr2), Strontium lactate, strontium chloride (SrCl2) USP38/NF33,strontium
ranelate
Uses: a Sedative and a treatment osteoporosis; and dentifrice.

References:

Baruthio, F. (1992). "Toxic effects of chromium and its compounds." Biological Trace Element Research, 32 (1-3), 145-153.
DOI 10.1007/BF02784599 by Humana Press.

Block, J. et al. (1974). Inorganic medicinal andpharmaceutical chemistry. Philadelphia: Lea & Febiger. Print.

Boullata, J. (2013). "Nutrients and associated substances". In Remington: the science and practice ofpharmacy.
Philadelphia, PA: Lippincott Williams and Wilkins. pp. 17131718.

Morgan, B. W., Todd, K. H., & Moore, B. (2001). "Elevated blood levels in urban moonshine drinkers". Annals ofEmergency
Medicine, 37(1), 51-4.

Reiss, J. (2000). "Genetics of molybdenum cofactor deficiency." Hum. Genet. 106: 157-163.
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