MT 120 LECTURE 2: VITAMINS AND TRACE ELEMENTS

Lectured by: Alessandra Kamille P. Mallari, MD, DPSP

Generalities
 There are about 23 vitamins and trace elements that are considered essential micronutrients.
 These are a collection of dietary heterogeneous ingredients necessary for health, development, and longevity (they are seen in a lot of
types of foods that we eat in our daily lives)
 Essential Micronutrients
o Very small amounts are required to satisfy their physiological roles and functions in the body.
o Critically needed in small amounts for metabolism of proteins, carbohydrates, fats, and for body structure.
 Vitamin C and E are antioxidants, Vitamin K is important in the body structure and bone matrix, while trace elements such as
selenium is important co-factor in a lot of body processes
o Deficiency and toxicity- often insidious and attributed to inappropriate intake (malnutrition) or defective utilization
 Definition of Terms
o Dietary Reference Intake (DRI)- reference values that provide quantitative estimates of the dietary level of each of the essential
nutrients
o Recommended Dietary Allowance (RDA)- average daily dietary amount sufficient for the nutrient requirements of most healthy
individuals (97-98%) categorized by age, gender and physiological need.
o Adequate Intake (AI)- is a recommended daily intake value when the RDA cannot be determined
o Tolerable Upper Intake Level (UL)- is the highest level
of daily nutrient intake likely to pose no risk of adverse
health effects for most individuals in the general
population

Vitamins
 Organic molecules (μg or mg) that are required for health,
growth, and reproduction.
 Except Vitamin D, the body depends completely on the
dietary intake for vitamins.
o Some enteric bacterial production of vit K, nicotinic
acid, riboflavin, biotin, cobalamin, and folic acid.
o Occur mostly in the colon and are not nutritionally
significant (poorly absorbed).
 Classified according their properties- function, nutritional
source or their solubility in water
o Water-Soluble easily absorbed, minimal storage
(toxicities rarely happens), deficiencies develop quickly
 Since most of the vitamins that we need are obtained
from the good we eat, removing one particular food
from the diet that is rich in a particular vitamin may
cause deficiency to occur.
 Easily excreted in the body, and the body has low
storage areas for this vitamin.
 Example: When taking Vit C tablet and upon
urination in the next few hours, urine will be intensely yellow in color, which is the Vit C being excreted in the urine.
 Thiamine, Riboflavin, Niacin, Pyridoxine, Cobalamin, Vitamin C, Folate, Pantothenic acid, and Biotin
o Water-Insoluble or Fat-Soluble depend on normal lipid digestion and micellar solubilization for absorption, such as the bile.
 Deficiencies do not develop as quickly as water-soluble, however they are much harder to absorb in the body because these type
of vitamins needs bile to absorb it into the body
 Examples: Patients who have removed their gallbladder (decreased bile) will have harder time absorbing these vitamins.
 Vitamins A, D, E, and K

Water-Soluble Vitamins
 Vitamin B1- Thiamine (Thiamine pyrophosphate/TPP)
o Function o RDA: M: 1.2 mg; F: 1.1 mg
 Essential cofactor of enzymes involved in carbohydrate amino acid intermediary metabolism
 Important for brain function.
o Cycle: Produced in colon by normal colonic bacteria. Bound to albumin in plasma when absorbed. Excess is excreted in the urine.
o Source: Yeast (bread, cakes, anything that uses yeast), legumes (peanuts), enriched grain products, and pork
o Testing
 Red blood cell transketolase activity with or without TPP- Useful test for assessing thiamine
deficiency
  Uses heparinized blood or fresh specimen
 Parenteral administration of thiamine- Most reliable method
o Toxicity: No toxicity is described
o Deficiency
 Infantile form- Occurs in infants that are breastfed for months without supplementation
 Manifest as cardiac failure may be sudden and rapidly fatal
 Alcohol abuse- Often associated with deficiency; Alcohol interferes with thiamine uptake and metabolism
 Poor nutrition- especially older people dependent on parenteral nutrition (incomplete parenteral nutrition)
 Early signs of deficiency: Anorexia, weight loss, muscle weakness, apathy, confusion, and irritability
 Late signs of deficiency: Edema and high output cardiac failure (wet beriberi), polyneuropathy with depressed reflexes,
paresthesias, weakness and muscle atrophy (dry beriberi), and psychosis (Wernicke-Korsakoff syndrome) characterized by
dementia, ataxia (coordination abnormality), and ophthalmoplegia (eyesight involvement).
 Vitamin B2- Riboflavin
o Riboflavin destroyed by light. o RDA: M: 1.3 mg; F: 1.1 mg
o Function
 Forms 2 coenzymes: flavin mononucleotide and flavin adenine dinucleotide
 Important role in electron transport in several oxidative systems.
o Cycle: Absorption is mostly in the jejunum.
o Source: Milk and dairy products, meat, poultry, fish and green vegetables. Bread and cereals are fortified with riboflavin
o Testing: 24-hour urine screen will indicate recent riboflavin intake.
o Deficiency
 Riboflavin is so prevalent in the diet that deficiency severe enough to cause marked debilities is not known.
 Mild riboflavin deficiency is common
 Occurs in association with a lack of thiamine and/or niacin  During infancy and childhood- impaired growth
 Prolonged deficiency: Cracking and swelling of the lips (cheilosis); cracking and inflammation of the angles of the mouth
(angular stomatitis); deep red smooth tongue, called magenta tongue (glossitis, that leads to atrophy); a greasy scaling of the
cheeks and the areas behind the ears (seborrheic dermatitis); and normocytic anemia
 Vitamin B3- Niacin
o 1 mg niacin = 60mg tryptophan o RDA: M: 16 mg NE/d; F: 14 mg NE/d
o Function
 Major role in the formation of nicotinamide adenine dinucleotide (NAD) and its phosphate (NADP) (byproducts in the
oxidation reactions in phosphorylation processes in the body like Kreb’s cycle, Tricarboxylic acid cycles)
 Important in intermediary metabolism and a large number of oxidation reactions
o Cycle: Urine is the main excretory path for niacin metabolites.
o Source
 Animal proteins are food high in tryptophan (e.g. meat, eggs and milk)
 Good sources for endogenously synthesized niacin
 Grains; except corn which is a poor source of tryptophan (niacin is bound and poorly available)
o Deficiency: Pellagra
 Common: Malnourished alcoholics and those who do not eat sufficient protein which become tryptophan deficient; Hartnup
disease (malabsorption syndrome of tryptophan) or carcinoid syndrome (tryptophan is consumed to make serotonin)
 Patients with Hartnup disease or carcinoid syndrome may produce mild symptoms of pellagra.
 Common in areas where corn is the staple food (Latin Americas)
 Characterized by: dermatitis, diarrhea, dementia, and, if untreated, death.
 Scaly dermatitis- can form on areas exposed to light or pressure (knees and elbows)
 The hands show a rough, scaly dermatitis with a glove like distribution and a pattern of hyperkeratosis,
vascularization, and chronic inflammation
 Pyridoxine and Riboflavin Deficiency increases the requirement for niacin because they are both cofactors
and are required for the synthesis of niacin (if pyridoxine and riboflavin are affected, niacin is also affected).
o Toxicity
 Excessive intake of niacin causes flushing (burning and itching of the face, chest and arms) and gastric irritation.
 Liver damage may result from very high doses.  Example: Used in the past to treat elevated cholesterol
 Vitamin B6- Pyridoxine
o Function: o RDA: M/F: 1.3 mg
 Coenzyme that participates in more than 100 transamination, decarboxylation, and other reactions
 Initial step of porphyrin synthesis  Amino acid transsulfuration
 Glycogen mobilization  Neurotransmitter synthesis
o Source
 Fortified cereals organ meats, muscle foods, potatoes, and fruits other than citrus.
 Cooking results in leaching (degradation) of the pyridoxine.
o Cycle: Urine is the major excretory pathway.
  Plasma pyridoxal 5-phosphate (PLP) is the major coenzyme form in the body and the primary form of circulating vitamin B6
on plasma (Normal: >30 nmol/L which indicates adequate status in adults)
o Testing
 Urinary 24-hour 4-pyridoxic acid level- reflects recent dietary intake of vitamin B6 status
 Urinary xanthurenic acid- after a tryptophan (methionine) oral load; indirect measure of functional vitamin B6 deficiency
o Deficiency
 Seen along with other vitamin or protein deficiencies and can occur in alcoholics.
 In patients who had overnight drinking sessions (high alcohol intake), sometimes these individuals can take vitamin B6
(pyridoxine) supplements to lessen (not to remove) the hangover symptoms.
 Uncommon and may cause microcytic hypochromic anemia.
o Toxicity: High doses of pyridoxine (>100 mg/d in adults) cause peripheral sensory neuropathy and possibly skin lesions.
 Vitamin B12- Cobalamin
o RDA: M/F: 2.4 ug
o Function: Complex cobalt-containing molecule, synthesized only by bacteria
 Cyanocobalamin and hydroxycobalamin are pharmacological forms.
 Adenosylcobalamin and methylcobalamin are the main biological forms.
 Main known cofactor roles:
 Synthesis of succinate from methylmalonate  Synthesis of methionine from homocysteine
o Cycle
 Absorption requires formation of a complex between cobalamin and intrinsic factor (in parietal cells of stomach).
 ¼ of plasma cobalamin are bound to transcobalamin, therefore available for transport to cells.
o Testing
 Plasma cobalamin <80 pg /mL- cobalamin deficiency
 Schilling test- Radiolabeled cobalamin used to measure absorption on different days (with or without intrinsic factor)
 Used to diagnose cobalamin deficiency before pernicious anemia.
 Cobalamin needs intrinsic factor produced by the stomach, so absence of intrinsic factors such as seen in pernicious anemia will
also result into the decrease in the absorption of cobalamin.
 Measure how much the patient absorbed or excreted cobalamin by measuring in urine (e.g. 100 units of cobalamin given to the
patient, and the patient excreted 100 units of cobalamin in the urine, this indicates that there is no absorption that happened)
o Deficiency
 Similar to folate deficiency: Impaired DNA synthesis resulting to megaloblastic anemia
 Neuropsychiatric damage- Not relieved and may even be worsened by folate treatment
 Folate (Folic Acid or Pterolyglutamic Acid)
o RDA: M/F: 400 ug (Pregnant women: 600 ug, Lactating women: 500 ug)
o Function
 Coenzyme role in one carbon transfer reactions.  Important for the maturation of erythrocytes.
o Source: Widely available from plants; green leafy vegetables, legumes,
cereals
 More than half of the folate content is lost during cooking.
o Deficiency
 Leads to impaired synthesis of purines and pyrimidines (which is
important in DNA synthesis)
 Causes megaloblastic anemia and leukopenia (DNA of these cells are
underdeveloped)
 In pregnant women: fetal neural tube defects- an abnormality that causes
any disruption in the formation of the brain and spinal cord
 Folic acid supplementation is important, especially in the 1st trimester
 Vitamin C- Ascorbate
o RDA: M: 90 mg/day; F 75 mg/day
o Function
 Powerful reducing agent, involved in oxidation reduction reactions and transfer of protons.
 Participates in the synthesis of chrondroitin sulfate and formation of the hydroxyproline of collagen.
 Important in wound healing (skin elasticity).  Biosynthesis of neurotransmitters and immune
function.
 Essential for gums, arteries and other soft tissues; bone (collagen synthesis); brain and nerve function (neurotransmitter and
hormone synthesis); nutrient metabolism (iron, protein and fat); and antioxidant defense and free radical scavenging.
 Found in leukocytes, adrenals, pituitary glands, and brain.
o Source: Fruits- citrus, berries, tomatoes, and vegetables; Loss in prolonged storage and overcooking
o Deficiency: Scurvy
 Characterized: bleeding gums, painful swollen joints, poor wound healing, confusion, fatigue and
diminished immune function (discovered in the 18th century).
 Mostly seen in alcoholics and elderly individuals with poor diet.
  Historically, common in sailors (rare in these days)- usually they have long expeditions, and they are at the sea for months, so
food is scarce, and they usually are in a poor diet (in British expeditions, sailors during that time died because of scurvy)
 Was called scurvy because the person who discovered it was James Lind, a Scottish surgeon who wrote about it in treaties.
o Toxicity
 Daily ingestion of >2000mg causes gastric and intestinal irritation and kidney stones, and can interfere with copper
metabolism.
 Humans are not able to complete the synthesis of ascorbate (usually are excreted in urine, causing a very acidic urine)
 Pantothenic Acid
o Function: Part of coenzyme A (CoA) and acyl carrier protein (ACP)- Both are carriers of acyl groups
 Acetyl CoA is involved in tricarboxylic acid (TCA) cycle.  CoA involved in the synthesis of lipids.
o Cycle
 It is transported in erythrocytes as coenzyme A (CoA).
 Highest tissue concentrations found in liver, adrenals, kidneys, brain, heart, and testes.
 CoA and ACP are metabolized to free pantothenic acid.
 Excreted in urine- Urine levels indicate dietary intake (Normal values: 2 mg to 7 mg/day)
o Source: Widely present in food
o Deficiency: Rare
 Occurs in severe malnutrition with other nutrient deficiencies.
 Burning Feet Syndrome- malnourished prisoners of war during WWII that responded to large doses of Ca pantothenate.
 Biotin
o Function: Coenzyme for several carboxylase enzymes:
 Pyruvate carboxylase- provides oxaloacetate for the TCA
 Acetyl CoA (Coenzyme A)  Carboxylase- for fatty acid synthesis
o Source: Found in many foods and large intestinal bacteria
o Deficiency: Rare
 Consumption of large amounts of uncooked egg whites can cause biotin deficiency, because of the presence of avidin.
 Avidin (antivitamin, present in large amounts in uncooked egg whites) which binds to biotin in the gut preventing absorption.
 Most common cause is failure to include biotin in parenteral nutrition
 Characterized by: Scaly dermatitis, glossitis, hair loss, anorexia, depression, and hypercholesterolemia

Fat-Soluble Vitamins
 Vitamin A and Retinol
o Function: Obtained from 2 compound classes:
 Preformed vitamin A, retinol, and related compounds
 Precursors β-carotene and related carotenoids (provitamins β-carotene found in yellow and red pigments in vegetables and
fruits)
o Source
 Retinol is seen in highest concentration in fish, liver, and leafy green vegetables
 Carotenoids are found in highest concentration in yellow-red pigmented vegetables (such as carrot and tomatoes)
o Retinol- For vision at low light intensities, synthesis of “active sulphate”, and reproduction
o Retinoic acid- cellular differentiation, morphogenesis, synthesis of glycoproteins, gene expression, immunity, growth and
prevention of cancer and heart disease
o Vitamin A- needed to maintain certain specialized cell membranes; for skeletal maturation; for the
formation of the light sensitive rods of the retina; and for the structure of cell membranes.
o Deficiency
 Frequent cause of blindness due to corneal damage (in poor regions of the world)
 Results in squamous metaplasia (may result eventually to dysplasia and formation of cancers if untreated)
 Earliest sign is vision loss in dim light (night blindness)
o Toxicity
 Liver and spleen are enlarged with lipid-laden macrophages, prolonged toxicity causes cirrhosis.
 Early symptoms: headache, hyperexcitability and bone pain  Lesions are reversible (if treated)
 Excessive carotene is benign- jaundice like discoloration
 Vitamin D (Cholecalciferol)
o Function
 UV light exposure of the skin converts naturally occurring 7-dehydrocholesterol to cholecalciferol
(or Vitamin D3)
 Homeostasis of calcium and phosphate (as a hormone), regulating intestinal adsorption, bone
mineralization.
 Promotes absorption of calcium and phosphate from the small intestine.
o Source
 The body can produce vitamin D (naturally occurring), some refer to it as a hormone
  A vitamin for people who are mostly staying indoors, especially in people living in the northern latitudes (in Scandinavian
countries) wherein they wear clothes that block sunlight reaching the skin.
 Cholecalciferol or Vitamin D3- diet derived from animal sources, fish, liver, and oils
 Ergocalciferol or Vitamin D2- derived from provitamin ergosterol found in fungi and plants and the major synthetic form used
to fortify milk and margarine.
o Cycle: Vitamin D2 and D3 require hydroxylation to the active form that occurs in liver and kidney.
o Deficiency
 Inadequate diet, insufficient sunlight, inadequate absorption, failure of conversion to the active
metabolite (i.e. chronic hepatic or renal disease)
 Any problems in the liver or kidneys will cause deficiency of vitamin D3.
 Bone lesion syndrome
 Rickets- in children before the epiphyses have closed  Osteomalacia- in adults (decreased bone density)
 Incidence of rickets and osteomalacia has declined in the addition of ergosterol in milk and other foods.

o Toxicity

Hypervitaminosis D- Due to ingestion of excessive vitamin D preparations
 Causes: hypercalcemia (sequelae: hypercalcuria, nephrocalcinosis, nephrolithiasis, and ectopic calcification of blood vessels)
 Early symptoms: weakness and headache
 Overexposure to UV can cause sunburn the skin, but this does not cause hypervitaminosis D.
 Sarcoidosis- Causes abnormal conversion of active metabolites
 Vitamin E (Tocopherol)
o Fat-soluble antioxidant or free radical scavenger- inactivates oxygen free radicals
o 8 naturally occurring forms; vitamin E is the only known lipid-soluble antioxidant in plasma and red cell
o Corn and soy beans are rich source
o Deficiency is very uncommon; may occur as a result of malabsorption, total parenteral nutrition, or premature infants
o There is no known toxicity.
 Vitamin K (Phytomenadione)
o Important in the activation of proteins in blood coagulation factor II, VII, IX, and X, Protein C, and Protein S.
o Deficiency result in defecting clotting and bleeding disorder.
o Vitamin K1- present in fresh green vegetables o Vitamin K2- produced by intestinal bacteria
o Dietary deficiency is uncommon, can occur in fat malabsorption, sprue, and biliary obstruction.

Trace Elements
 Trace elements are metals, except for selenium, halogen, fluoride, and iodine.
 Referred to as trace elements because long ago when the term was coined, quantitation in tissue was
not possible. But now, with the advanced chemistry/analytic machines, trace elements can now be
quantitated.
 Essential trace elements are those that result in an impairment of normal health, function, and
development. Even in the absence of these will cause abnormalities (they are essential to life).
 The roles of the trace mineral elements include structural, signal transduction, and catalytic properties. Some of the trace mineral
elements are components of metalloenzymes, function as enzyme cofactors, provide electron and oxygen transport in the body.
 10 trace mineral elements have been generally recognized as essential in humans.
 It is difficult to create a deficient model because of the ubiquitous
distribution of these elements in the environment and food supply,
which frequently causes contamination of the testing system, and
because only minute amounts are needed to support physiologic
processes.
o Very hard to quantitate the normal values for because very minimum
amount is needed in the body.
 Deficiencies
o Due to nutritional deficiency; inadequate supplementation in total
parenteral nutrition; or a disease state.
o Due to interaction between trace elements (e.g., zinc and copper) and with other nutrients (e.g., zinc and vitamin A) interfering
with absorption or adversely affecting metabolic utilization.
o Genetic defects: Menkes’ kinky hair syndrome (copper), congenital atransferrinemia (iron), acroder matitis enteropathica
(zinc), and xanthine and sulfite oxidase deficiencies (molybdenum).
 Chromium
o Function
 Enhance the action of insulin.  After absorption; binds to plasma transferrin
 Absorption of chromium from the intestines is low.  Stored in liver, spleen, other soft tissues, and bone.
o Source: Meat, whole grains, green beans, broccoli and spices
 o Deficiency: Patients receiving parenteral nutrition. Prolonged deficiency is associated with increased cardiovascular risk.
o Chromium depletion is thought to be associated with increased cardiovascular risk, and supplementation has
demonstrated increased HDL cholesterol and decreased insulin (anti-diabetic and helps promote good cholesterol)
o Hexavalent Chromium- a recognized carcinogen
 Industrial material used in leather tanning, stainless steel, and dyestuff industries.
 Associated with lung cancer, renal failure, dermatitis, and skin ulcers.
o Test:
 Air monitoring for Cr6+ is the usual way to test
 Increased chromium in urine is confirmation of recent occupational or environmental exposure to chromium.
 Cobalt
o Cobalt (Co) is essential for humans only as an integral part of vitamin B12 (cobalamin) metabolism.
o Cobalt has no other known function in humans. o Diet has to supply the human vitamin B12 needs.
o Microflora of the human intestine are not able to use cobalt to synthesize cobalmine; free cobalt does not impact with the body’s
vitamin B12 pool.
 Copper
o 3rd most abundant trace element in the human body, following zinc and iron.
o It is a very effective cation in reactions that involve electron transport and binding to organic molecules.
o Function
 Electron transport and oxidation reactions and is essential for cellular respiration; neurotransmitter regulation; collagen
synthesis; nutrient metabolism, especially iron; and as an antioxidant against free radicals.
 Mostly as a component of the cuproenzymes and copper-containing proteins
 Copper-containing plasma amine oxidases catabolize- tyramine, histidine, and polyamines, and inactivate the catecholamines
(norepinephrine, tyramine, dopamine, and serotonin).
 Lysyl oxidase helps collagen proteins crosslink into larger fibers
 Cytochrome C oxidase, catalyzes the cellular utilization of oxygen
 Extracellular superoxide dismutase (lungs, thyroid, and uterus)
 Copper/zinc dismutases (brain, thyroid, liver, pituitary, and erythrocytes)
 Copper-containing proteins include ceruloplasmin, albumin, and transcuperin, which transport copper; metallothionein,
which sequesters and stores copper; and clotting factor V
o Sources
 Rich sources of copper include liver, shellfish, chocolate, nuts, and seeds.
 The average daily copper intake: 1.6 mg in males and 1.2 mg in females. Adults should get at least 0.9 mg/day.
 Smoking, strenuous exercise, infections, and injuries increase the need for copper.
o Metabolism:
 Copper absorption- copper is absorbed in the stomach and especially in the small intestine
 Absorption is decreased by excessive zinc or iron intake. Too much copper will also cause iron deficiency.
 Bile adds about 5 mg/day to the ingested copper.
 Transported bound to albumin and transcuperin- rapidly cleared by the blood into the liver
 Ceruloplasmin (65-90% of plasma copper)
 Metallochaperones- transport intracellular copper into each of the cells for cellular consumption (for metabolic needs)
 Free Cu- source of oxygen free radicals, in very low amounts
o Cycle:
 Total copper in adult: 50-80mg; mainly concentrated in the liver and muscle
 Main organ containing highest amount: Liver (30-50 ug/g dry tissue)
 Serum levels: F: 49-184 μg/dL; M 59-118 μg/dL (affected by diurnal variation, peaks in the morning)
 Excretion- feces (unabsorbed dietary copper, and biliary and gastrointestinal secretions; small amounts sweat, urine, and saliva)
o Disease: Menkes’ Syndrome
 Recessive X-linked defect of copper absorption (ATP7A mutation, most commonly seen in males)
 Onset usually occurs by 3 months of age.
 Characterized by:
 Poor mental development, failure to keratinize hair, skeletal problems, and degenerative changes in the aorta.
 The brittle hair (steely) is kinky or twisted, and there is poor skin and hair pigmentation, hypothermia, and seizures.
 Copper deficient with decreased serum and liver copper. RBC copper is normal, since they are unable to absorb copper.
o Disease: Wilson’s Disease
 Autosomal recessive disease with an impaired biliary excretion of copper (ATP7B mutation)
 There is excess copper in the body, which leads to buildup of copper in the different organs of
the body, particularly in the eyes, kidneys, and the brain.
 Presents in individuals between 6 and 40 years of age.
 Characterized by:
 Sclerosis, abnormalities of kidney, cornea and brain
 Often presenting with acute or chronic or fulminant hepatitis due to the accumulation of copper in the body.
  Neurologic disorders and Kayser-Fleischer ring of the cornea
 Fluoride
o Used to prevent dental carries.
o Fluoridation of drinking water now reduces the incidence of tooth decay for more than 60% of the U.S.
population, and reduces the incidence of tooth decay by more than 60%.
o Dental Fluorosis
 Unsightly mottling of dental enamel
 Seen in erupting teeth of children due to excessive fluoride
 Iron (most abundant trace mineral element in the body)
o Usually present in hemoglobin, myoglobin, storage iron, and tissue iron. Iron in the body is stored as ferritin and hemosiderin.
o Rigorous conservation of iron occurs.
o Ferritin- storage form of iron seen in all cells; hepatocytes and macrophages of the marrow
o Hemosiderin- formed when ferritin is broken down. o Apotransferrin- transport form of iron
 Manganese
o Important in the formation of connective tissue and boney tissue and CHO and lipid metabolism
o Constituent of important metalloenzymes.
o Source: Whole grain foods, nuts, leafy vegetables, soy, and teas.
o Cycle: Absorbed in small intestine to liver bound to albumin.

Deficiency
o

Rare in a normal diet

Results in low plasma cholesterol, impaired glucose tolerance, skeletal abnormalities, dermatitis, color changes in hair, and
abnormal clotting.
o Toxicity: Neurologic abnormalities- similar to Parkinson’s disease
 Molybdenum
o Important in metalloenzymes and other enzymes such as sulfite oxidase and xanthine dehydrogenase.
o Source: Grains, nuts, and legumes such as peas, lentils, and beans are good sources
o Cycle: Renal homeostatic regulation occurs, and urine output directly reflects dietary intake.
o Deficiency and Toxicity:
 Rare in healthy people on a normal diet  Low toxicity in human
 Selenium
o A constituent of glutathione peroxidase- associated with vitamin E and its function
o Nonmetal and important in oxidative stress protection and regulation of thyroid hormone.
o Source: Grains, nuts, and legumes such as peas, lentils, and beans are good sources
o Cycle: Renal homeostatic regulation occurs, and urine output directly reflects dietary intake.
o Deficiency and Toxicity
 Keshan disease
 Pediatric patients, causing endemic cardiomyopathy, in areas with low soil selenium levels
 Skeletal muscle disorders with proximal weakness and serum creatinine elevation.
 Immunodeficiency can result from selnoprotein deficiency.
 Toxicity- garlic breath, hair loss, irritability and mild nerve and nail damage
 Zinc
o Normal body stores: F: 1.5 g; M: 2.5 g (distributed in all tissues)
o 2nd to iron as the most abundant trace element in the body. o Most common catalytic metal ion in the cytoplasm of
cells.
o Intracellular metal, found in 60% in skeletal muscle and 30% in bone.
o Cofactor for 300 enzymes
o Important in protein and nucleic acid synthesis and essential for gene activation.
o Zinc containing metalloenzymes include carbonic anhydrase, alkaline phosphatase, RNA and DNA polymerases, reverse
transcriptase, thymidine kinase, carboxypeptidases, alcohol dehydrogenase, and superoxide dismutase.
o Source: Ubiquitous in food. Oysters are especially rich in zinc, and other shellfish and meats are good sources.
o Metabolism:
 Absorption- occurs in duodenum (high calcium and low protein = decreased zinc absorption)
 Metallothionein regulates zinc transfer in the small intestine into intracellular
 Blood- zinc is bound to albumin and a2-macroglobulin (Reference range: 10-17 umol/L)
o Excretion: Intestine (<1 mg/day) and urine (<0.5 mg/dL)
o Deficiency:
 Common in patients with diabetes mellitus, alcohol abuse, malabsorption syndromes, and liver and kidney diseases
 Symptoms are general because of the many enzymes and tissues affected.
 Nutritional zinc deficiency
  Syndrome of growth retardation, male hypogonadism, skin changes, mental lethargy, hepatosplenomegaly, iron deficiency
anemia, and geophagia (eating clay)
o Zinc toxicity is rare in humans.
o Testing:
 No single test is definitive for the status of zinc stores
 Inductively coupled plasma-mass spectrometry (ICP-MS)- reference test for zinc in serum, plasma and other samples (70-120
ug/dL)
o Zinc levels in RBC and hair- provide long term assessment of body zinc