Essential Minerals: Magnesium

Essential Minerals

• Minerals include magnesium, phosphorus, zinc, nickel, manganese, molybdenum, selenium, cobalt, chromium, lithium, fluoride, and iodine
• Minerals are categorized into major elements and trace elements
• Major: calcium, magnesium, phosphorus, sodium, potassium, chloride, sulphur
• Trace: iron, iodine, copper, manganese, zinc, molybdenum, selenium, fluoride
• Minerals can be necessary with unknown function, nonessential and present in tissues or toxic.
• Necessary: chromium, nickel, bromine, lithium, barium
• Nonessential: rubidium, silver, gold, bismuth
• Toxic: aluminum, lead, cadmium, mercury

Magnesium (Mg)

• Total body content of magnesium is 25 grams
• 60% is in bone
• Recommended Daily Allowance (RDA) is 400 mg/day for men
• Sources include green leafy vegetables and cereals
• Normal magnesium serum level ranges from 1.8 to 2.2 mg/dL
• Biochemically functions include acting as an activator of enzymes like alkaline phosphatase, hexokinase, fructokinase, and phosphofructokinase
• Magnesium decreases neuromuscular irritability.
• Magnesium is a constituent of bone and teeth
• Magnesium is involved in insulin sensitivity
• Hypomagnesaemia is defined as a magnesium level less than 1.7 mg/dL

Causes of Hypomagnesaemia

• Reduced intake such as dieting and unbalanced diet
• Vomiting and diarrhea
• Liver cirrhosis
• Increased excretion such as alcoholism, laxative abuse, and treatment with diuretics or digitalis
• Impaired absorption due to gastrointestinal diseases

Clinical Features of Hypomagnesaemia

• Neuromuscular irritability
• Cardiac arrhythmias
• Tremors
• Carpopedal spasm

Causes of Hypermagnesemia

• Excess intake orally or parenterally
• Renal failure
• Hyperparathyroidism
• Oxalate poisoning
• Rickets
• Multiple myeloma
• Dehydration
• Use of drugs like aminoglycosides, antacids, calcitriol, and tacrolimus

Phosphorus (P)

• Total phosphorus content in the body is 1 kg
• 80% is in bone and 10% in muscle
• Primarily an intracellular element
• Daily requirement is 500 mg
• Sources include milk and cereals and meat
• Normal serum level is 3.4 - 4.5 mg/dL in adults, 5-6 mg/dL in children.
• 40% circulates as free ions, 50% complexed with other ions, 10% is protein bound
• Fasting level is higher post prandial level
• Whole blood level is 40mg/dl
• Renal threshold is 2mg/dl

Biochemical Functions of Phosphorus

• Bone and teeth formation
• Production of high-energy phosphates
• Synthesis of nucleoside coenzymes
• DNA & RNA synthesis
• Production of phosphate esters
• Activation of enzymes
• Formation of buffers

Serum Calcium and Phosphate Combinations

• Increased P with decreased Ca seen in hypoparathyroidism and renal disease
• Increased P with normal or increased Ca seen in milk alkali syndrome and hypervitaminosis D
• Decreased P with increased Ca seen in hyperparathyroidism and sarcoidosis
• Decreased P and Ca seen in malabsorption, vitamin D deficiency and renal tubular acidosis

Causes of Hyperphosphatemia

• Increased absorption of phosphate due to excess vitamin D or phosphate infusion
• Increased cell lysis
• Decreased excretion of phosphorus due to renal impairment or hypoparathyroidism
• Other: Hypocalcemia ,massive blood transfusions and Thyrotoxicosis
• Intake of Chlorothiazide, Nifedipine and Furosemide drugs.

Causes of Hypophosphatemia

• Decreased absorption of phosphate
• Malnutrition
• Malabsorption
• Chronic diarrhea
• Vitamin D deficiency
• Intracellular shift: Insulin therapy, glucose phosphorylation, respiratory alkalosis
• Increased urinary excretion of phosphate: Hyperparathyroidism, Fanconi's syndrome, hypophosphatemic rickets
• Other: Hereditary hypophosphatemia, hypercalcemia, chronic alcoholism.
• Use of Antacids, Diuretics and Salicylate intoxication.

Sulfur

• Sulfates mainly come from the amino acids cysteine and methionine
• Sulfur Functions:
• Disulfide bridges hold polypeptide units together in insulin and immunoglobulins
• Chondroitin sulfates are in cartilage and bone
• Keratin is sulfur-rich, found in hair and nails
• Enzymes/peptides have -SH at active site, e.g., glutathione
• Coenzymes from thiamine, biotin, pantothenic, and lipoic acid contain sulfur
• The total quantity of sulfur in urine is about 1 g/day
• Sulfur is categorized as:
• Inorganic Sulfates: 80% of excretion, proportional to protein intake
• Organic Sulfate or Ethereal Sulfate: 10% of urinary sulfates, representing putrefactive activity in the intestine, proportional to protein intake
• Neutral Sulfur or Unoxidized Sulfur: 10% of total sulfates, present in organic compounds like amino acids, thiocyanates, and urochrome

Zinc (Zn)

• Dietary sources include milk and dairy products, liver, egg, unmilled cereals, and pulses
• Absorption occurs in the duodenum
• Stored in metallothionein
• Excreted in pancreatic juice and to a lesser extent through sweat

Biochemical functions of Zinc

• Zinc-dependent enzymes: carboxypeptidase, carbonic anhydrase, alkaline phosphatase, lactate dehydrogenase, ethanol dehydrogenase, and glutamate dehydrogenase.
• RNA polymerase contains zinc is required for protein biosynthesis.
• Functions as an antioxidant as zinc is extracellular superoxide dismutase-dependent
• Wound healing properties

Additional Functions of Zinc

• Insulin storage and secretion as insulin stores in beta cells of pancreas which stabilizes the hormone molecule
• Commercially available preparation-protamin-zinc-insulinate (PZI) also contains zinc
• The taste sensation of the Zinc-containing protein, Gusten, in saliva is important for taste sensation
• Supports growth/reproduction where growth retardation and gonadal hypofunction are seen in Zn deficiency

Zinc Deficiency

• Results in poor wound healing and skin lesions like hyperkeratosis and dermatitis
• Impaired spermatogenesis and alopecia can occur
• Reduction in number of T and B lymphocytes
• Macrophage function is retarded
• Associated with depression, dementia, and other psychiatric disorders
• Binds with amyloid to form a plaque in Alzheimer's

Zinc Deficiency Symptoms

• Leukonychia punctate are white spots in fingernails
• Acrodermatitis enteropathica presents as a rare inherited disorder
• Defect in Zn absorption, autosomal recessive
• Causes include inflammation around mouth, nose fingers. diarrhea, alopecia, ophthalmoplegia and hypogondasim

Zinc Toxicity

• Toxicity occurs at intakes >1000 mg
• In welders, inhalation of zinc oxide fumes is toxic
• Ingestion of rat poisons may lead to toxicity
• Chronic poisoning includes gastric ulcer, pancreatitis, anemia, nausea, vomiting & pulmonary fibrosis
• Acute poisoning includes fever, excessive salivation, head ache, leukocytosis & anemia

Selenium (Se)

• The plant source depends on the nature of soil in which food crops are grown
• UGA codon for direct insertion of seleno-cysteine into selenium containing enzymes
• Seleno-cysteine is directly incorporated into protein during biosynthesis
• Seleno-cysteine may be considered as the 21st amino acid
• Daily requirement: 50–100 μg/day
• Normal serum level: 50–100 μg/dL

Selenium Functions

• Glutathione peroxidase (GP): important selenium containing enzyme
• Thyroxin is converted to T3 by 5'-de-iodinase
• Selenium deficiency leads to hypothyroidism
• Acts as a nonspecific intracellular antioxidant
• Selenium action is complementary to vitamin E
• Availability of vitamin E reduces the selenium requirement

Additional Selenium Functions

• Selenoprotein P is a highly basic protein with multiple histidine residues
• Functions as a transporter of selenium as an antioxidant
• Functions as Thioredoxin reductase, NADPH dependent enzyme which helps maintaining redox status inside cell

Selenium Deficiency Diseases

• Keshan disease is seen in Keshan province in China as soil has a deficiency in selenium
• Characterized by multifocal myocardial necrosis, cardiac arrhythmias and cardiac enlargement
• Isolated selenium deficiency in other parts of the world causes liver necrosis, cirrhosis, cardiomyopathy and muscular dystrophy
• Kashinbeck disease is an endemic human osteoarthropathy in low selenium zones, specifically in Eastern Asia
• Results in Degenerative osteoarthrosis in children 3-13 years old
• Characterized by Shortening of fingers and long bones with dysfunction of joints

Selenium Toxicity

• Selenosis: Selenium toxicity that is present in metal polishes and anti-rust compounds
• Toxicity symptoms include hair loss, falling of nails, diarrhea, weight loss, and garlicky odor in breath
• Garlic odor in breath is due to dimethyl selenide in expired air

Iodine

• 80% is in the thyroid gland
• Normal level is 5 - 10 μgm/dl
• RDA is -150-200microgram/day
• Dietary sources include drinking water, sea food, milk, meat, vegetables, cereals
• Absorption occurs in the small intestine

Metabolic Role of Iodine

• Growth and reproduction
• Biological role of iodine is in formation of thyroid hormones, thyroxine (T4) and tri-iodo thyronine (T3).

Goitrogens

• Ingredients in foodstuffs, that prevent utilization of iodine seen in cassava, maize, millet, bamboo shoots, sweet potatoes ,beans
• Cabbage and tapioca contain thiocyanate-inhibits iodine uptake by thyroid
• Mustard seed contains thiourea, which inhibits iodination of thyroglobulin

Iodine Deficiency

• Can cause Goiter and Hypothyroidism
• Results in Growth retardation and impaired mental function
• May also cause Spontaneous abortion and still birth
• Can be a cause of Neurological and myxodematous cretinism
• Squint
• Nystagmus

Fluorine

• Dietary sources include drinking water, sea fish, cheese, tea, Jowar
• Safe limit of fluoride -1ppm in water
• Absorption in the small intestine
• Excreted in the urine

Functions of Fluorine

• Development of bone & teeth
• Prevention of dental carries
• Topical application will result in a fluoroapatite that protects enamel from the decay by acid
• Fluoride ions enter hydration shell surrounding apatite crystals thus teeth are more resistant to plaque bacterial attack

Fluoride Abnormalities

• Intake >2ppm results in intestinal upset, gastro enteritis, loss of weight, loss of appetite
• Intake >5ppm causes mottling of enamel, stratification and discoloration of teeth

• 10ppm intake causes fluorosis

• Alternating areas of osteoporosis and osteosclerosis, with brittle bones
• Genu valgum (Knock-knee) is the characteristic feature
• Ingested fluoride accumulates in bones

Prevention of Fluorosis

• Use fluoride free water
• Restrict intake of Jowar
• Supplementation of Vitamin C
• Regulation of fluoride containing tooth paste

Manganese

• Sources: Nuts and tea leaves; fruits & vegetables; and animal sources like liver
• Absorption is inhibited by iron
• In blood, manganese is bound to transmanganin(beta globulin)
• Excreted through bile

Biochemical Functions of Manganese

• Enzymes either contain or are activated by manganese, like hexokinase, phosphoglucomutase, pyruvate carboxylase
• Involved in isocitrate dehydrogenase, succinate dehydrogenase, arginase, glutamine synthetase, and Mn-dependent superoxide dismutase
• Integral part of glycosyl transferases
• Responsible for synthesis of glycoproteins and chondroitin sulfate
• Required for RNA polymerase activity

Manganese Deficiency

• Causes impaired growth and skeletal deformities
• Chondroitin sulfate generation is also impaired so that organic matrix of bone and cartilage becomes abnormal

Molybdenum

• Mean dietary intake: 100 microgram/day
• Sources in cereals and liver
• Xanthine oxidase and aldehyde oxidase contain molybdoprotein, (a substituted pterin to which molybdenum is bound by two sulfur atoms)

Molybdenum Disorders

• Deficiency - depression of xanthine oxidase, increased excretion of xanthine and decreased uric acid excretion
• Associated with increased incidence of esophageal cancer
• Molybdenum Toxicity - excess intake-Molybdenosis that results in growth retardation, anemia and diarrhea

Cobalt

• Vitamin B12 - only important nutrient for human beings that contain cobalt
• Stimulates production of erythropoietin
• Prolonged use in animals has resulted in polycythemia

Nickel

• Normal plasma level is 0.5 microgram/dl
• RDA is 500 microgram/day
• Nickel containing enzymes such as urease and methylcoenzyme reductase inhibit acid phosphatase
• Necessary in production of pigments in fish, birds and insects
• May be carcinogenic in higher concentrations
• Deficiency: decreased utilization of iron

Chromium

• Total body content is 6 mg
• Blood level is 20 nanogram/dl
• RDA is 30 microgram
• Radioactive (57Cr) -widely used to tag RBC
• Tagged RBCs when injected back to patient, can be seen in circulation and rate of hemolysis could be calculated.
• Used to demonstrate cytolytic effect of T lymphocytes and NK cells

Chromium Disorders

• Deficiency: impaired glucose tolerance and impaired growth leading to decrease in fertility and sperm count
• Toxicity: causes liver and kidney damage and is also carcinogenic

Chromium & Glucose Tolerance

• Chromium containing protein chromodulin facilitates binding of insulin to its receptor and receptor kinase signaling.
• Chromium deficiency leads to impaired glucose tolerance
• Efficiency of binding of insulin to its receptors on the peripheral cells is improved by chromium.

Lithium

• Lightest alkali metal
• Essential growth factor in tissue culture
• Normal human skeletal muscles contain 2–200 ng/g of weight
• Higher concentrations are seen in the brain
• Mean intake is 50 mg/day

Lithium Use and Toxicity

• Used for Treatment of manic depressive psychosis (bipolar disorders)
• Will counteract both mania and depression
• Therapeutically optimum concentration in plasma is -7–10 micrograms/mL
• A concentration of 12 micrograms is toxic
• Narrow margin of safety
• Requires constant monitoring of blood level
• Inhibits inositol phosphatase➔increased concentration of inositol phosphate in brain.
• Elevates serotonin levels and reduces catecholamines in brain tissue
• Toxicity can cause hypothyroidism, hyperparathyroidism and kidney damage