Vitaminology & Trace

Elements

Abayomi O. Akanji
Professor of Clinical Pathology
Faculty of Medicine
Kuwait University
 What are Trace Elements?

Trace elements are those elements that

occur in human and animal tissues in
mg/kg amounts or less.

Essential when:
– deficient intake ►impairment of function
– restoration with physiological amounts of only
that element prevents/alleviates impairment.
 Classification of Trace Elements
 Defined biochemical functions + signs of deficiency
in humans
 Fe, Zn, Cu, Co, I, Mo, Se, fluoride
 Signs of deficiency; no clear biochemical functions
 chromium, boron
 Clear biochem function; no clear deficiency signs
 manganese
 No clear biochemical functions/ deficiency signs
 Ni, Si, Va, arsenic, Br, Pb, tin, Li
 Trace Element Functions
 amplification- small amounts produce dramatic effects on
the body e.g. Fe deficiency & anaemia

 specificity- cannot be effectively replaced by chemically

similar constituents

 homeostasis- regulated mechanisms for absorption,

storage and excretion - storage proteins such as ferritin
& metallothioneins important in regulation of Fe, Zn, Cu

 interactions- overabundance of one trace element can

interfere with metabolic use of another e.g. large dietary
Zn affect Cu absorption.
Assessment of trace element status
• clinical response to therapeutic supplementation
• measurement of metalloenzyme activities
• tissue levels, but usually invasive to obtain
– Hair & fingernails often used, but subject to environmental
contamination, tap water, shampoo, soap
– other body fluids : blood, RBC, urine, saliva, semen - but levels
do not always effectively reflect tissue status
• levels of binding proteins:
– caeruloplasmin for Cu
– ferritin for Fe.

*VERY IMPORTANT TRACE ELEMENTS STUDIED ELSEWHERE* -

IRON - haematology, anaemia; IODINE - thyroid hormones
 Copper
- essential trace metal present in many intracellular enzymes
e.g. cytochrome oxidase, superoxide dismutase, tyrosinase,
- present in plasma in association with the copper-binding protein,
caeruloplasmin.

Balance: (next slide)

Laboratory Assessment:

1. serum copper : ~10-22 µmol/L, ~ 90% bound to caeruloplasmin

2. serum caeruloplasmin - normal adult levels 200-600 mg/L
- an acute phase reactant.
- levels useful in interpretation of serum copper levels.
3. urinary copper : ~ 0.1µmol/day
Copper balance
Cu deficiency: typically found in:
- Premature babies : copper stores in liver laid in 3rd trimester
- adults : malabsorption e.g. after intestinal surgery,
prolonged parenteral nutrition

Cu toxicity : usually iatrogenic ►renal tubular damage

Inborn Errors of Cu Metabolism:

Wilson’s disease (hepatolenticular degeneration):

• results from copper deposition in liver, brain, kidney, and lens of eyes
• defect in gene encoding for enzyme responsible for Cu excretion
in bile and urinary reabsorption
• high urinary and tissue Cu, low serum Cu & caeruloplasmin

Menke’s Syndrome : rare and fatal

• presents in children as growth failure, mental retardation, bone and
vascular lesions, hair and skin changes.
• X-linked genetic defect in copper transport and storage
• ▼serum, liver, brain Cu, ▼caeruloplasmin & cytochrome oxidase activity
Biochemical Changes in Wilson’s disease
 Zinc
 essentialtrace metal present in up to 200
metalloproteins with a wide variety of functions
e.g. carbonic anhydrase, RNA/DNA polymerases,
alcohol dehydrogenase, alkaline phosphatase, steroid
hormone receptors
 present in all protein-rich foods
in plasma, bound to
Albumin 90%
α2-macroglobulin 10%
major role in protein synthesis, gene expression,
stabilization of nucleic acids and subcellular
organelles and wound healing.
Zinc Balance
Laboratory Assessment of Zinc Metabolism
1. serum zinc: < 5.0 µmol/L = deficiency
– Levels fall during an acute phase reaction to injury or infection

2. Other body tissues and fluids:

- urine, saliva, semen, hair, RBC, WBC

3. best demonstration of marginal zinc deficiency

- positive response to supplementation

Inborn Disorders of Zinc Metabolism

1. Acrodermatitis enteropathica : retarded growth, hypogonadism,

dermatological and ophthalmic lesions, GIT disturbances.
- Low serum Zn + symptoms reversed by Zn supplementation

2. Sickle cell disease : ? reason

Skin lesions in zinc deficiency – acrodermatitis enteropathica
Acquired Disorders of Zinc Metabolism

Zinc deficiency
• Associated with:
- pregnancy: from increased fetal demands
- Nutritional: low zinc diet with high fibre content
- chronic alcoholism: increased urinary zinc excretion
- GIT disease; malabsorption; prolonged parenteral nutrition

• Features: growth retardation, testicular atrophy, oligospermia,

hepatosplenomegaly, dermatitis, poor wound healing.
• Reversed by Zn supplementation.

Zinc toxicity : uncommon

• usually iatrogenic from environmental exposure (zinc fumes).
• Accidental ingestion : GIT symptoms.
Chromium
• essential trace metal, important in glucose and lipid
metabolism
• potentiates insulin action –
– deficiency ►insulin resistance
• present mainly in meats and whole-grain products
• in plasma, bound to β-globulins, specifically transferrin

Balance :
• poorly absorbed in upper small intestine - only 0.3-2.0% of
dietary intake.
• Significant occupational exposure from steelmaking,
electroplating leather tanning and photographic industries
Disorders of Chromium Metabolism

Laboratory Assessment :
serum chromium: 0.12-2.10 µg/L
urine chromium: 100 - 200 ng/day
Others : hair 0.1-4.1 µg/g
RBC 20-36 µg/L
Chromium deficiency :
Causes : - GIT disease and malabsorption
- prolonged parenteral nutrition
Features : insulin resistance;
Reversed by Cr supplementation.
Chromium toxicity :
usually iatrogenic from occupational exposure
►allergy, conjunctivitis, dermatitis, GIT symptoms, hepatitis.
Selenium
• present in enzymes: glutathione peroxidase, thyroxine deiodinase
• important as an anti-oxidant and in thyroid hormone metabolism
• present mainly in meats, dairy, cereals and grains
• in tissue, present as selenocysteine and selenomethionine

Laboratory Assessment :
• serum selenium: 46-143 µg/L; urine selenium: 7.0-160 µg/L
• Others: hair 0.2-1.4 µg/g; RBC 75-240 µg/L
• Assay of RBC glutathione peroxidase activity

Selenium deficiency :
Causes : - GIT cancer, pregnancy, protein-calorie malnutrition
- prolonged parenteral nutrition
Associated with : Keshan disease - an endemic cardiomyopathy in China
Kashin-Beck disease : endemic osteoarthritis in China
Selenium toxicity:
• associated with loss of hair and nails, skin lesions, CNS abnormalities.
Fluoride
• unique action in preventing tooth decay
• inorganic fluoride readily absorbed in small intestine and
distributed almost entirely in bones and teeth.
• tightly regulated by renal excretion
• significant dietary contribution from drinking water
• other sources: seafood, tea, cow milk, cereals
• excessive intake : mottled teeth, skeletal changes,
ligament calcification

Laboratory Assessment :
concentrations : serum: 10-200 µg/L;
urine : 0.2-3.2 mg/L;
RBC: 450 µg/L
•Manganese
– constituent of many metalloenzymes –
• arginase, pyruvate carboxylase, superoxide dismutase
– activator for enzymes:
• hydrolases, kinases, decarboxylases
– associated with formation of connective & bony tissue, reproduction
& growth functions, CHO & lipid metabolism
– widely distributed in tissues
• highest concns in bone, liver, pancreas
– poorly absorbed from small intestine
– homeostasis maintained primarily through biliary excretion
Significance
- proven role in manganese-dependent enzymes
- No direct evidence of human manganese deficiency.

Cobalt: only known function: integral component of vit B12

Molybdenum: in metallo-enzymes: xanthine oxidase, aldehyde oxidase
- no well-defined cases of dietary human deficiency
 Vitamins
• Definition:
– unrelated organic catalysts that are not endogenously
synthesized but necessary in trace amounts for normal
metabolism
• Classification:
– Water soluble:
• B-Complex: B1 (thiamine), niacin, folate, riboflavin (B2),
pyridoxine (B6), cyanocobalamin (B12),
• Others: ascorbate (C)
– Fat-soluble:
• A (retinol), D (cholecalciferol), K (phytomenadione), E
(tocopherol)
 Vitamin deficiency
Causes:
– Inadequate intake with normal requirements
– Impaired absorption
– Impaired metabolism (e.g. vitamin D)
– Increased requirements e.g. pregnancy
– Increased losses

• Deficiencies typically multiple

• Vitamin deficiency ► mobilization of body stores ► tissue depletion

► biochemical impairment (sub-clinical deficiency ► frank deficiency

• Functions typically intracellular

• Plasma concns do not reflect intracellular levels or function –
unreliable
• Tissue concns most reliable but not always easily available
Water-soluble Vitamins– folate & B12 not considered here

Vitamin sources function

B1 Whole grain cereals, Cofactor in metabolism of pyruvate
organ meats, flours, and 2-oxoglutarate and in pentose
thiamine nuts, green vegs phosphate shunt (transketolase)
B2 Milk, organ meats, Oxidation-reduction enzymatic
riboflavin eggs, green vegs actions
B6 Meat, poultry, fish, Enzyme systems –amino acid
pyridoxine potatoes, vegetables transaminases, phosphorylases,
decarboxylases
niacin Whole grain, meat, fish, Coenzymes – NAD, NADP – in
legumes, nuts, cereals, glycolysis and oxid phosphorylation

C- Citrus fruits, tomatoes, Antioxidant, formation of connective

ascorbate melons, cabbage, straw tissue & catecholamines; cholesterol
berries, green vegs metabolism
Fat-soluble Vitamins

Vitamin sources function

A - retinol Animal – fish liver oils, Vision, growth of epithelia, immune
butter, milk, liver, eggs responses, reproduction, anticancer
Plants – green/yellow agent; constituent of retinal pigment
vegs, margarine, fruits rhodopsin
E– Vegetable oils, wheat Antioxidant – membrane stability,
tocopherols germ, rice germ, nuts, cardiovascular disease prevention,
legumes, green vegs RBC function; fertility
K- Green vegetables, Coagulation factors – prothrombin,
spinach, cabbage, liver, VII, IX, X; osteocalcins – binding of
synthesis in intestine calcium to proteins
D– Fish liver oils, fortified Calcification of bone and teeth (will
calciferol milk, sun exposure, be considered in greater detail later)
small amounts in butter,
eggs, liver, salmon
VITAMIN DEFICIENCIES
Complications of Vitamin A deficiency
LESIONS RESULTING FROM VITAMIN A DEFICIENCY
LESIONS IN RICKETS
Complications of Thiamine (vitamin B1) Deficiency (Beri-beri)
Complications of Niacin Deficiency (Pellagra)
Complications of Riboflavin (vitamin B2) Deficiency
Complications of Ascorbate (Vitamin C) Deficiency
LESIONS IN SCURVY
Classification of Vitamins
Hypervitaminosis
Classically seen with fat-soluble vitamins: A, D
Seen with excessive vitamin nutritional supplements
• Hypervitaminosis A
– Acute toxicity: neurologic symptoms: headache,
vomiting, stupor, papilloedema
– Chronic toxicity: neurologic, skeletal (loss of cortical
bone), cutaneous (fissuring, ulcers), hepatomegaly with
parenchymal damage.
– Symptoms subside with discontinuation of excess vit A
intake
• Hypervitaminosis D: ▲intestinal absorption of Ca, PO4
► hypercalcaemia, hyperphosphataemia, bone resorption
►renal calculi, osteoporosis, metastatic calcification