TUMS

Azin Nowrouzi, PhD

Minerals in nature
There are 92 naturally occurring elements on earth but only eight elements make over 98% of the minerals on the Earth's crust. They are, in decreasing quantity, 1 oxygen, 2 silicon, 3 aluminum, 4 iron, 5 calcium, 6 sodium, 7 potassium, 8 magnesium. The graph below shows you the amounts of these elements in the Earth's crust.

Minerals in human body

Minerals are elements of the periodic table More than 25 have been isolated from the body. 22 elements have been shown to be essential (excluding C,H, and O) minerals make up about 4 to 5% of body weight (for a 70 kg individual: 2.8 kg) many minerals are found in ionic form (others as ligands or covalent compounds) 3

Minerals (function)
Minerals = Inorganic elemental atoms that are essential nutrients and electrolytes.
1.

Nutritionally essential
Serve both structural and functional roles in the body.
Structural minerals (calcium and phosphorus) are the major inorganic matrix of bone and teeth. Functional minerals (calcium, phosphorus and all the others) 1. Participation in all cellular activities 2. Serve as enzyme cofactors or in oxidation/reduction reactions. 3. Maintain the delicate cellular fluid balance 4. Maintain the acid-base balance in body fluids 5. Control the osmolarity in the fluid compartment 6. provide for electrochemical nerve activity 7. Regulate muscle tone and activity (including organ muscles like heart, stomach, liver, etc

2.

Nutritionally beneficial
Effects of boron in the presence of Vitamin D depletion

3.

Pharmacologically beneficial
Fluoride to prevent dental caries Lithium salts to treat maniac depression

Minerals and Toxicity

Minerals are stored in bone and muscle tissue
So toxicity is a possibility although it is rare.
Occurs when one isolated mineral is ingested without any supportive cofactor nutrients. Toxic levels accumulate only if massive overdoses are used for a long period of time.

There is a dose-effect relationship.

Classification
Macro or Major minerals
Sodium, potassium, magnesium, calcium, phosphorus, sulfur, chloride

Micro or Trace minerals (body needs relatively less)

Chromium, manganese, iron, cobalt, molybdenum, copper, zinc, fluoride, iodine, selenium, silicon, tin, arsenic, nickel

Present in body tissues at concentrations >50 mg/kg (50 ppm)

Present in body tissues at concentrations <50 mg/kg (50 ppm)

Those present at ( g/dL) in body fluids or (mg/kg) in tissue = Trace elements Those found at ng/dL or g/kg = Ultratrace elements 6

Important minerals
Macro Element Ca P K Na Cl S Mg g/kg 15 10 2 1.6 1.1 1.5 0.4 Trace Element Fe Zn Cu Mo Se I Mn Co
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mg/kg 20-50 10-50 1-5 1-4 1-2 0.3-0.6 0.2-0.5 0.02-0.1

Minerals Homeostasis
Varying dietary intakes; so mechanisms of mineral homeostasis include:
1. Regulation of intestinal absorption. 2. Transport systems in blood. 3. Uptake and storage mechanisms in tissue.
There are specific metalloproteins for transport and safe storage of very reactive metal ions; examples: Metallothionein (Cu, Zn) Transferrin, ferritin, hemosiderin (Fe) Ceruloplasmin (Cu) Feces (Cu, Zn), Urine (halides as I, F and Se, B, Mo, Cr), Hair, Nails, Skin cell desquamation.
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4. Control of excretion.

Food as source of minerals

Bioavailability of minerals in intestines
Found in all food groups. More reliably found in animal products. Often other substances in foods decrease absorption (bioavailability) of minerals: Oxalate, found in spinach, prevents absorption of most calcium in spinach. Phytate, form of phosphorous in most plants; In the plant, this molecule is a regulator of signaling in the cell; and in seeds, it acts as a phosphate storage molecule. It binds such minerals as calcium and iron and zinc very well, and since it is not digested, animals that consume grains with phytate will lose these minerals as the phytate passes through their gut.
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Antagonistic interactions
Dietary calcium aggravates phytic acid blocking of zinc absorption by forming insoluble Ca-Zn-phytate complex. Zinc ions block copper (Cu) absorption
Formation of intestinal metallothionein that binds copper. Pharmacological use in Wilsons disease.

Molybdate ion forms insoluble Cu-Mo complex, limits Cu absorption.

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Synergistic interactions
Interaction between selenium and iodine.
Important for thyroid function. Deiodinase enzymes are selenoproteins, remove iodine from T4 to form T3, Glutatione peroxidase = a selenoprotein in thyroid in removing H2O2.

Selenium deficiency is exacerbated by Vitamin E depletion. Zinc and Vitamin A are interrelated.
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Mineral interaction

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Factors affecting requirements

1. Physiological state/level of production 2. Interactions with other minerals 3. Tissue storage

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(1)Sodium
RDA (recommended daily allowance): 0.5 g ADI (average daily intake): 5 g Above 45 mg per day interferes with riboflavin and phosphorus uptake. One of the three main electrolytes in the body. Deficiency symptoms: excessive sweating, chronic diarrhea, nausea, respiratory failure, heat exhaustion, impaired carbohydrate digestion. Functions:
Fluid balance Neuromuscular excitability Maintenance of viscosity of blood Role in resting membrane potential Role in action potential

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Sodium absorption
Occurs by sodium pump situated in basal and lateral plasma membrane or intestinal and renal cells. Na-pump actively transports Na into extracellular fluid.
Total sodium Unexchangeable (complexed in bone) Exchangeable Extracellular Intracellular Plasma 4000 mmol 30% (70%) 135 -145 mmol/L 4 10 mmol/L 135-145 mmol/L

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Simplified potassium daily balance

Fluid Na+ K+ 4 140 Ca2+ Mg2+ 5 1 3 58 Cl103 4 Amino Glucose acids mg% 5 40 90 0-20 Extracellular 142 Intracellular

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Potassium is the major intracellular cation (150 mEq/L). Extracellular fluid (ECF) and the normal concentration of plasma potassium is 3.5 to 5.5 mEq/L (or 20mg/dl). Total body content of potassium is about 200 mg/dl or 50 mEq/Kg (40 mEq/kg in females). Disruption of potassium balance usually caused by:
Increase in renal, gastrointestinal, or skin losses which produce negative balance. Decreases in renal excretion which produces a positive balance.

K++ is actively transported in exchange for Na++ by Na++-K++-ATPase.

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(2)Potassium
RDA: 3500 mg ADI: 2500 mg Up to 5 grams is safe. Plasma concentration of K+ is 3.5-5 mEq/L. Functions:
Influences muscular activity Involved in acid-base balance Important for cardiac function Cofactor for certain enzymes (pyruvate kinase) Neuromuscular irritability and nerve conduction process

Individuals with kidney diseases should not take supplemental K. K on empty stomach can cause nausea. Processing of foods fills it with sodium. Diet is better to be high in K and low in Na. K+ balance in the kidney:
Acute regulation: Hormonal control; Release of insulin uptake of K+ by cells Chronic regulation: K+ adaptation 17

Potassium inside the kidney

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Factors that regulate the distribution of potassium

Potassium concentration in ECF depends on:
1. External balance (matching daily intake and output) 2. Internal balance (distributing potassium between extracellular and intracellular fluid)

Factors Regulating Internal balance (Plasma Potassium) Factors Regulating External balance (Body Potassium Content)
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Factors Regulating Plasma Potassium (Internal Balance)

1. Blood pH
Acidemia causes a shift of K+ from the intracellular space of cells into the plasma. Alkalemia causes a shift of K+ from the plasma into cells. Plasma K+ may rise about 0.6 mEq/L for each decrease in pH of 0.1 units. Different types of acids result in different magnitudes of potassium shifts
shifts in the distribution of potassium usually do not result from acidosis caused by nonmineral or organic acidosis

At constant blood pH, infusion of sodium bicarbonate leads to a decrease in plasma potassium concentration

2. Insulin
Insulin is the first-line defense against hyperkalemia. A rise in plasma K+ stimulates insulin release by the pancreatic beta cell. Insulin, in turn, enhances cellular potassium uptake, returning plasma K+ towards normal. plasma potassium and insulin participate in a feedback control mechanism.

3. Catecholamines
Beta-2-agonists lower plasma potassium (by causing a cellular uptake of potassium). Alpha agonists increase plasma potassium concentration.

4. Physical Conditioning and Exercise

Strenuous exertion may injure muscle cells and allow leakage of K+ into the ECF.

5. Activity of Cell Membrane Na-K ATPase

insulin, physical training, catecholamines may exert their effect by altering the activity of the sodium potassium ATPase in

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Factors Regulating Body Potassium Content (External Balance)

1. Renal Excretion of K+
The Kidney can rapidly excrete large loads of potassium, 200-300 mEq/day, without a change in plasma K+ or body K+ content. Potassium is filtered freely at the gomerulus but 90-95% is reabsorbed in the proximal tubule The major site of renal regulation of potassium excretion occurs in the distal tubules and collecting ducts the ability to reduce excretion to zero or very low levels is slow, taking perhaps 2 to 4 weeks Aldosterone
Aldosterone stimulates distal nephron secretion of potassium. In the absence of aldosterone, body potassium content and plasma K+ are increased due to a decrease in renal excretion of potassium An increased plasma K+ stimulates aldosterone secretion and decreased plasma K+ suppresses it. Increase urinary flow rate increases urinary potassium excretion Sodium delivery to distal nephron may promote K+ excretion (Na-K exchange) Sulfates and others create favorable electrical (lumen negative) gradients for passive secretion of potassium into the urine Increased plasma K+ leads to an increased rate of secretion Alkalosis leads to an increase in the K+ concentration of the cells of the distal tubule, this leads to a more favorable gradient that is associated with increased urinary secretion of potassium. Acidosis has the opposite effect.

major determinants of urinary potassium excretion include:

Urine Flow Rate

Urinary Sodium Concentration Non Reabsorbable Anions (Urinary Cl- Concentration) Plasma K+ Concentration pH of the Blood

2.

Gastrointestinal Potassium Excretion

Normally 10 15% of K+ intake is excreted by the gut. Aldosterone is one of the regulators of secretion of potassium by the gastrointestinal tract. Diarrhea increased fecal K+ losses, particularly laxative-related diarrhea. Diarrhea may contain 100 mEq/L of K+ Working in hot temperatures may produce up to 10-12 liters of sweat per day containing 10 mEq/L of K+. Thus major K+ losses may occur via this route. Sweat K+ is also under control of the hormone aldosterone.

3.

Skin Potassium Excretion

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Consequences of Hypokalemia
Metabolic effects: Hypokalemia supresses insulin release glucose intolerance. K+ deficiency in children retards growth. Cardiovascular effects: Electrophysiologic abnormalities changes in EKG

Decreases amplitude or inversion of the T wave Increases amplitude of the U wave Prolongation of the Q-U interval Increased amplitude of the P wave, prolongation of the P-R interval Widening of the QRS complex 22

Consequence of Hyperkalemia
Cardiac effects: Acute rise in plasma K+ raises cell membrane potential toward threshold potential. ECG effects:

ca. 6 mEq/l increased amplitude of T wave with shortened Q-T interval ca. 7-8 mEq/l widening of QRS complex, decreased amplitude of P wave with eventual loss of P wave following these changes ventricular fibrillation, cardiac standstill. 23

(3)Magnesium
RDA: 350 mg/day
pregnancy and lactation: 450 mg

Second most plentiful cation in intracellular fluids. Normal plasma Mg concentration ranges from 1.4 to 2.1 mEq/L (0.70 to 1.05 mmol/L).
~50% of total amount in bone. ~45% in muscle and nervous tissue. ~ 5% in extracellular fluids. blood plasma magnesium : ~ 2 -3 mg/dl.
60% is ionized 10% complexed with other ions 30% bound with proteins

a. Functions in more than 300 enzyme systems:

cofactor of all enzymes involved in phosphate transfer reactions that use ATP and other nucleotide triphosphates such as: phosphatases pyrophosphatases 24

Magnesium
b. Most metabolically active tissues: brain, heart, liver and kidney
Essential for the conversion of vitamin D to its biologically active form to help absorb and use calcium. Prevents cardiovascular disease. CNS (central nervous system):
hypomagnesemia ---- CNS irritability, disorientation, psychotic behavior, convulsions.

neuromuscular system:
magnesium has a direct depressant effect on skeletal muscle. magnesium also causes a decrease in Ach release at motor end plate (used in treatment of eclamptic seizures). Abnormally low concentrations of Mg in the extracellular fluid ---increased Ach release ---- increased muscle excitability (tetany).

Effective against Chronic Fatigue syndrome (CFS), and noiseinduced hearing loss.

Prevents the calcification of soft tissue Bone strength and springiness food sources: all green plants (chlorophyll); meats 25

Transcellular shifts under acidosis and alkalosis

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(4)Roles of Chloride in the Body

1. 2. 3. 4. 5. 6.

Chloride is an essential mineral for humans. Chloride is the major negatively charged ion of the extracellular fluid. The normal serum (ECF) range for chloride is 98 - 108 mmol/L. The suggested amount of chloride intake ranges from 750 to 900 milligrams per day Total obligatory loss of chloride in the average person is close to 530 milligrams per day. Functions as an electrolyte,
plays a key role in maintaining proper water distribution, osmotic balance

7.

Combines with hydrogen in the stomach to make hydrochloric acid. On average, the stomach produces 2 liters of HCl daily
break down of proteins absorption of other metallic minerals activation of intrinsic factor, (absorption of vitamin B12)

8.

Chloride is transported into the gastric lumen, in exchange for another negatively charged electrolyte (bicarbonate), in order to maintain electrical neutrality across the stomach membrane. Exchange of chloride and bicarbonate, between red blood cells and the plasma helps to govern the pH balance and transport of carbon dioxide from the body. With sodium and potassium, chloride works in the nervous system 27 to aid in the transport of electrical impulses throughout the body.

9. 10.

CO2 transport

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Chloride shift

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(5)Calcium
RDA: 1200 mg ADI: 743 mg. Above 2500 mg per day may stress the kidneys, kidney stones. In the elementary composition of the human body, it ranks fifth after oxygen, carbon, hydrogen, and nitrogen Most Ca is contained in bones, about 1% is used for nerve impulses and muscle contraction. Deficiencies are linked to high blood pressure (Populations with low
calcium intakes have high rates of high blood pressure).

Calcium reduces symptoms of premenstrual syndrome (PMS), protects against colon cancer. If inadequate intake, body steals Ca from bones. Resorption of Ca2+ and Na+ go in parallel. The site of resorption of Ca2+ is entire nephron except (!!!!) thin part of loop of Henle !!!! The site of fine adjustment: late distal tubules. Parathyroid hormone (PTH) and 1,25-(OH)2-calciferol (calcitriol) decrease ca2+ excretion.
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(6)Phosphorus

ADI: 1500 mg
Adults: 800 mg/day Pregnancy and lactation: 1200 mg/day

Megadoses cause body to lose Calcium. 800 grams of P in body; 88% in bones (structural).
12% is very active metabolically: Energy transfer, Acid-base balance, Enzyme action.
High energy phosphate compounds Nucleic acids Phospholipids Phosphoproteins Coenzymes (vitamins)

metabolism of RBC, ATP production.

Found in many foods.

Slight fall in PO4 after a carbohydrate rich meal. Deficiency (hypophosphatemia) not common. 80 95% are reabsorbed, mainly in proximal tubule

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(7)Sulfur
Structural part of most proteins
Most sulfur in the diet comes in from protein sources containing sulfur amino acids such as cysteine, cystine and methionine. Some enters as inorganic sulfur (sulfate, sulfide, chondroitin sulfate and certain other sulfate esters) Sulfur is also present in thiamine, biotin, sulfolipids, conjugated bile acids and coenzyme A Found in anticoagulant heparin and in chondroitin sulfate, and glucosamine sulfate.

Takes part in enzymatic, antibody and tissue activities. Deficiency: degeneration of collagen, cartilage, ligaments and tendons.32

(8)Iron
RDA: 15 mg

More than 100 mg daily, there is risk of infection and toxic side effects. 70% of iron in body is functional; found in enzymes and other molecules.
>80% of this found in red blood cells.

30% of iron is in storage depots or transport proteins. 2 types of body iron:

heme iron
hemoglobin, myoglobin, catalases, peroxidases, cytochromes (a, b and c involved in electron transport), cytochrome P450 (involved in drug metabolism)

non-heme iron
ferritin, hemosiderin, hemofuscin, transferrin, ferroflavoproteins, aromatic amino acid hydroxylases.
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Iron distribution and storage

Carried in blood stream via transferrin (a globulin)
Transferrin and transferrin receptor (TfR)

Stored in 2 forms:
ferritin hemosiderin

Stored in liver, spleen, bone marrow, intestinal mucosal cells and plasma
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Cellular uptake of iron

Transferrin and transferrin receptor (TfR)

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Iron absorption and elimination

There is no mechanism for excretion of iron. Iron is normally lost by exfoliation of intestinal mucosal cells into the stools. Trace amounts are lost in bile, urine and sweat (no more than 1 mg per day). Bleeding (vaginal, intestinal) is a more serious mechanism of elimination.
50% of women are iron deficient. 36

Iron deficiency
Initial symptoms are vague and ill-defined
easy fatigability lack of appetite headache dizziness palpitations

then: hypochromic-microcytic anemia

microcytosis (small RBCs) hypochromia (poor fill of hemoglobin) poikilocytosis (bizarre shapes) anisocytosis (variable sizes)

Low Fe levels correlated with akathisia (Greek word meaning cant sit down) or the restless leg syndrome (RLS) Over supplementation with Fe causes recurrent illnesses in athletes and infants. 37

Iron deficiency
A deficit in total body iron Three stages of iron deficiency are:
Iron depletion: earliest stage
Not recognizable by the patient Storage iron (serum ferritin) is decreased or absent. Serum iron and hemoglobin concentrations are preserved.

Iron deficiency without anemia

Additional decrease in iron storage (stores, serum ferritin, are almost exhausted) Low serum iron Low transferrin saturation Erythrocyte protoporphyrin increases. Hemoglobine falls to the lowest limit of normal But without frank anemia

Iron deficiency anemia (hypochromic microcytic anemia)

Most advanced stage Hemoglobin or haematocrit continues to fall Decreased or absent iron stores Decreased serum iron and transferrin saturation Erythrocyte protoporphyrin increases to upper limit of 38normal

 Causes: 1. Increased intestinal absorption

Iron overload

Either acutely (as in iron poisoning) Chronically (southern Africa brew their beer in iron vessels (Bantu siderosis).

2. Increased parenteral iron administration 3. Repeated blood transfusions

for treatment of refractory anemias Hemochromatosis (when iron overload is associated with damage to cells. a hereditary disease characterized by improper

Two broad types of iron overload disorders.:

processing by the body of dietary iron which causes iron to accumulate in a number of body tissues, eventually causing organ dysfunction. Periodic

phlebotomies (venesection). Hemosiderosis (without cell damage) Excess iron is deposited mainly as hemosiderin in RE cells in the liver and spleen (harmless) but with time parenchymal deposition may lead to hepatic fibrosis and myochardial damage. 39

(9)Copper (Cu)
RDA: 1.5 mg 3.0 mg. Cu1+ and Cu2+ in biological systems. High dosage (15 to 35 mg) could adversely affect Zinc metabolism. High concentrations are found in brain. Found in organ meat, liver, kidney, shellfish, nuts, cocoa containing products, whole grain cereals. Important trace elements, involved in many body functions:
Helps build bones and blood, elastin, collagen. Involved in healing process, energy production, hair and skin coloring, taste sensitivity. Needed for healthy nerves and joints.
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Cu functions
1. 2. 3. 4. Energy Production Cytochrome c oxidase is a multi-subunit complex containing copper and iron and is essential for oxidative phosphorylation. Connective tissue formation Lysyl oxidase is a cuproenzyme essential for stabilization of extracellular matrixes. Enzymatic crosslinking of collagen and elastin. Iron metabolism Ferroxidase I (ceruloplasmin) and ferroxidase II, oxidize ferrous iron to ferric iron. Central nervous system Dopamine monooxygenase (DMO) requires copper as cofactor and ascorbate as electron donor. It catalyzes conversion of dopamine to norepinephrine, important neurotransmitter. Monoamine oxidase catalyzes the degradation of serotonin in the brain and is involved in the metabolism of catecholamine. Melanin synthesis Tyrosinase is copper-containing enzyme, present in melanocytes and catalyzes synthesis of melanin. Antioxidant functions SODs (superoxide dismutase) are Cu and Zn containing enzymes that convert superoxide radical to H 2O2. Regulation of gene expression Cu-dependent proteins act as transcription factors
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5. 6. 7.

Inborn errors of copper metabolism

Menkes disease: Impaired intestinal transport of copper caused by mutation in ATP7A gene leads to severe copper deficiency. Wilsons disease: Mutation in ATP7B gene affects incorporation of copper into ceruloplasmin and copper excretion, leading to accumulation of copper in liver, brain, kidney, cornea, other tissues. Aceruloplasminemia: Failure in hepatic synthesis of ceruloplasmin. Carciovascular disease: due to deficiency in animals, but in humans increased plasma copper is a cardiovascular risk factor. 42

(10)Fluoride
99% is found in bones and teeth Functions (cariostatic activity and anti-osteoporotic activity):
Interacts with hydroxyapatite to form fluorhydroxyapatite that less acid soluble. promotes the remineralization of enamel in early caries. Inhibits bacterial growth in mouth decreases cavity formation.

Fluoride is thought to have osteoblastic activity and, in partnership with calcium, stimulates the production of new bone.
Calcium needs F and nine other elements to build bone. promotes mineralization of calcium and phosphate.

Molybdenum combined with F is more effective in fighting cavities. New and improved toothpastes are on their way to market. Main sources include drinking water and plants (spinach, lettuce, onions). Added to water in 0.7-1.2 mg/L (ppm). >2ppm intestinal upset. Excess can cause mottled enamel (fluorosis) (> 5ppm).

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(11)Iodine
RDA: 150 mcg 25-30 mg in the body. 5-10 g/dl blood. Not toxic up to 2000 mcg daily, but may exacerbate acne. Iodine is necessary for the formation of thyroid hormones (T-4 and T-3) Regulation in body:
30% of Iodine in food is absorbed. Excess removed in urine.

Salt water fish best food source. Even breathing sea air prevents goiter. Iodine can be absorbed by the skin. Some food prevent utilization of iodine (called goiterogenous substances); for example, cabbage contains thiocyanate which inhibits iodine uptake by thyroid. Deficiency: Goiter (less severe)
Enlarged thyroid gland due to bodys attempt to increase thyroid hormone production.

Cretinism (more severe)

Severe iodine deficiency during pregnancy serious problems in baby.
Stunted growth, deaf, mute, mentally retarded.

To prevent the development of endemic goiter, table salt has been spiked with sodium iodide. 44

(12)Zinc
RDA: 15 mg to 19 mg, ADI: 8.6 mg Toxicity is low up to 500 mg/day. Zinc absorption appears to be dependent on a transport protein, metallothionein. Helps fight acne. Similar results to tetracycline in superficial acne and good results in deep acne. For blemish-free skin. Deficiencies include poor growth, delayed wound healing, impairment of sexual development and decreased taste acuity
zinc is present in gustin, a salivary polypeptide that is necessary for the development of taste buds.

Deficiency Acrodermatitis Enteropathica Adverse effects: Inhibits copper utilization, increase plasma cholesterol.
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Biological roles
Part of every cell. Over 200 enzymes depend on Zn (over 20 metalloenzymes):
Carbonic anhydrase Carboxypeptidase A
Four types of proteases Serine Cysteine Aspartic acid Zinc

ACE (angiotensin I convering enzyme) RNA and DNA polymerases

Important for body immunity (fights common cold) and strength. Male sexual function, male hormone metabolism, sperm formation, sperm motility. Deficiency may cause infertility. Vital role during pregnancy; Dose should increase; problems:
premature births, low birth weight, growth retardation, preeclampsia (pregnancy-induced hypertension), small head circumference.
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Zinc Fingers

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(13)Manganese
RDA: 2.0 to 5.0 mg ADI: 2.7 mg Total body Mn is 15 mg.
Maximum concentration is in liver. In blood it is bound to transmanganin (specific carrier protein). In the cells, it is seen inside nuclei complexed with nucleic acids.

Low levels of toxicity causes permanent insanity. Industrial manganese dust, causes locura manganica (manganese madness). Role in proper bone and cartilage formation and glucose and lipid metabolism, and reproductive functions.
Deficiency causes similar bone problems as osteoporosis.

Dietary sources: Whole grain foods, nuts, leafy vegetables, soy products, teas.
3% is absorbed Absorption inhibited by iron. 75% lost when wheat is refined to white flour. Excreted through bile and pancreatic juice.

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Manganese functions
Maganese is an activator of several different enzymes:
Phosphoglucomutase Isocitrate dehydrogenase Cholinesterase Intestinal peptidase Carboxylases ATPases Superoxide dismutase (SOD) Pyruvate carboxylase Arginase Glycosyl transferases (responsible for synthesis of glycoproteins and chondroitin sulfate, organic matrix of bone and cartilage) hexokinase However, magnesium and cobalt can replace Mn in several enzymes.
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(14)Boron
Before 1981 it was thought to be unimportant. But it is essential for:
normal growth hormones involved in bone metabolism normal balanced levels of estrogen and testosterone.

A study:
Within 8 days of boron supplementation of 3mg, postmenopausal women showed 40% less loss of Ca and 33% less loss of Mg through urine.

Supplementation causes:
increase in 25-(OH) cholecalciferol, decreased calcitonin, decreased serum glucose, increased serum triglycerides

Boron has not yet been included in Essential Nutrient list and no RDA intake levels has been given. 50

(15)Chromium
RDA: 50 g -200 g. Trivalent chromium (Cr3+) is very safe Hexavalent industrial Cr6+ is toxic and carcinogenic. In 1957, Cr was identified as the active component of glucose tolerance factor (GTF).
Very important but Cr was added to the list of RDA handbook in 1989.

Signs of Cr deficiency resemble Type II diabetes (a cofactor for insulin?)

Important in normal glucose, insulin, fatty acid metabolism and muscle growth. 98% of Cr is destroyed when flour is refined; May be why adult diabetes is winning.

Helps lose fat and gain muscle.

It makes even pigs to lose weight.

Helps raise HDL cholesterol or the Good Cholesterol

Prevents cardiovascular disease.

Found in: meat, whole grain products, green beans, broccoli, some spices, corn oil, clams, drinking water (variable)
Foodstuff rich in sucrose and fructose are low in chromium.

High doses of Chromium picolinate, dietary supplement can damage 51 kidney and liver.

(16)Lithium
Optimum concentration in plasma is 7-10 g/ml. It is an essential growth factor at least in tissue culture.
Human skeletal muscle contains 2-200 nanograms/g of wet weight. Higher concentrations are seen in nerves, and brain. Helps transport sodium metabolism in brain, nerves and muscles.

Deficiency symptoms: Nerve, mental disorders. Higher intrauterine and neonatal deaths. Therapeutic uses: Paranoid schizophrenic.
Lithium toxicity leads to hypothyroidism. Lithium treatment caused increased [inositol phosphate] in brain by inhibiting inositophosphatase.

Natural sources: Seafood

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(17)Molybdenum
RDA: 50 g to 250 g ADI: 109 g Toxicity starts at 10 mg daily, causing gout-like disease. Dietary sources: legumes, peas, lentils, beans nuts
Meats, fruits and many vegetables are poor sources.

Component of several enzymes involved in alcohol detoxification, uric acid formation, sulfur metabolism.
Sulfite oxidase (catalyses the last step in degradation of sulfur amino acids) Xanthine dehydrogenase Aldehyde oxidase flavoproteins, xanthine oxidase (oxidizes xanthine to uric acid).

Low levels are associated with esophageal cancer and methionine intolerance.
Anticancer effect stems from role in detoxification of cancer causing chemicals. Enhances fluoride in cavity prevention. Small amounts of Mo helps in utilization of copper. High Mo can cause copper deficiency. 53

(18)Selenium

RDA: 70 mcg, ADI: 108 mcg Only a small amount is needed. Megadoses cause toxicity: hair and fingernail loss. Works as antioxidant with Vitamin E to destroy hyperoxides, free radicals that damage cell membranes. Fights cancers (respiratory and gastrointestinal), cardiovascular disease, diabetes, arthritis. Some biologically active compounds contain selenocysteine, where Se is substituted for S in cysteine.
Selenocysteine is now considered the twenty-first amino acid with the codon UGA.
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Functions of Selenium
Component of glutathione peroxidase (GSHPx-1 GSHPx-4)
catalyzes removal of hydrogen peroxide

GSH + H2O2

GSSG + H2O

GSH = reduced glutathione GSSG = oxidized glutathione Component of iodothyronine-5- deiodinase

Converts T4 to T3

Improves killing ability of neutrophils.

Reduces the prevalence and severity of mastitis (inflammation of the breast)

Selenoprotien P (Se carrier in plasma) Selenoprotein W (in muscle)

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Selenium ...
Selenium deficiency can cause cataract.
Because lens depends on superoxide dismutase catalase glutathione peroxidase adequate levels of Vitamin E, Vitamin C and selenium.

Keshan disease (cardiomyopathy) in Keshan region of China Kashin-Beck disease (Big Bone Disease). China Reproductive disorders Mood disorders
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(19)Silicon
ADI: 329 mg Nontoxic. But high levels observed in Alzheimers disease. After oxygen, Silicon is the most abundant element on earth. Regarded as essential element in 1972. Silicon breast implants are toxic. As a nutrient, Silicon is important for normal bone growth, integrity of skin.
appears to play an important role in the development and maintenance of cartilage (chondroitin sulfate, hyaluronic acid, keratin sulfate). may have a protective role in cardiovascular diseases (atherosclerosis).

Anti aging. Colloidal silicic acid causes improvements in thickness of skin, strength of the skin, wrinkles, and health of hair and nails. 57 Found in unrefined grains and beer.

(20)Vanadium
RDA: 10 mcg to 60 mcg. Excessive amounts lead to cramping and diarrhea. Essential role in human nutrition: it improves insulin action and even mimics the functionality of insulin. Deficiency during pregnancy: kids with serious birth defects, bone deformity, death. Less milk in mothers. natural source: Fish Therapeutic uses: heart attack prevention, high blood pressure, arteriosclerosis, diabetes. may also function as an oxidation-reduction catalyst.
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(21)Tin
Produces accelerated growth in deficient rats. Tin is similar to carbon in its tendency to form covalent bonds. May have a role with heme-containing enzymes: largest quantities are found in kidneys and skin and the thymus gland. human intake: ~ 1.5 - 3.5mg/day
heme oxygenase cytochrome P-450

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(22)Cobalt, essential part of Vitamin B12

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Functions of Cobalt and Vitamin B12

Essential coenzyme for
Propionate metabolism
methylmalonyl CoA to succinyl CoA

DNA synthesis Bacterial synthesis of methionine

Microflora of human intestine cannot use cobalt to synthesize physiologically active cobalamine.
Human vitamin B12 requirements must be supplied in the diet Free (nonvitamin B12) cobalt does not interact with the body vitamin B12 pool.
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NPK Fertilizers
NPK fertilizers have reduced soil quality because they can replace only nitrate/phosphate/potassium in the soil and not many other minerals that are essential for human growth.

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Definition of terms
RDA: Recommended Daily Allowance. FDA: Food and Drug Administration ADI: Average Daily Intake Dietary intakes of trace elements can be assessed by direct dietary analysis and by taking dietary histories. To estimate positive or negative balances: Direct measurement of total dietary intake over several days + measurement of output in urine, feces and other routes
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