A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

268 VITAMINS AND TRACE ELEMENTS
doses of vitamin C taken chronically have resulted in calcium
oxalate urolithiasis. There is theoretical concern that high
doses of vitamin C (in common with other anti-oxidants) can
have pro-oxidant actions.
Pharmacokinetics
Ascorbic acid is well absorbed following oral administration
and its sodium salt may be given by intramuscular or intravenous
injection. Ascorbic acid is mainly metabolized by oxidation
to oxalic acid. Normally about 40% of urinary oxalate is
derived from ascorbic acid. When the body stores of ascorbic
acid are saturated, some ingested ascorbic acid is excreted in
the urine unchanged.
VITAMIN E (TOCOPHEROL)
Vitamin E is found in many foods, including nuts, wheatgerm
and bananas. Deficiency in animals causes abortion and degeneration
of the germinal epithelium of the testes. No defined
deficiency syndrome exists in humans, but low vitamin E
intake is associated with anaemia in premature and malnourished
infants. Vitamin E protects erythrocytes against haemolysis,
and is a fat-soluble anti-oxidant and detoxifies free radicals.
Free radicals cause membrane and epithelial injury and have
been implicated in the pathophysiology of numerous diseases,
including cancer and atheroma. Epidemiological studies suggested
that reduced vitamin E intake is associated with
increased atherogenesis (Chapter 27). Large studies of vitamin
E supplementation for a number of cardiovascular disorders
and cancers have not shown clear benefit, and there is a theoretical
risk that prolonged ingestion of high doses could be
harmful.
Key points
Vitamin deficiency and disease
• In general, vitamin deficiencies are due to inadequate
dietary intake or malabsorption.
• Vitamin B deficiencies do not often occur in isolation.
• Vitamin A deficiency causes night blindness.
• Vitamin B 1 (thiamine) deficiency causes beriberi
(neuropathy, paralysis, muscle wasting and cardiac
failure).
• Vitamin B 3 (nicotinic acid) deficiency causes pellagra
(photosensitive dermatitis, diarrhoea, dementia and
death (the 4 Ds)).
• Vitamin B 12 deficiency causes megaloblastic anaemia,
dementia and neuropathy.
• Vitamin C deficiency causes scurvy (perifollicular
petechiae, gingivitis and swollen joints).
• Vitamin D deficiency causes rickets (in young) and
osteomalacia (adults).
• Folate deficiency causes megaloblastic anaemia and
neural tube defects (in the developing fetus).
Key points
Population groups at high risk for vitamin deficiency
• Infants
• Pregnant women
• Elderly people, especially the elderly with chronic
disease
• Alcoholics and drug abusers
• Vegans and undernourished populations
• Patients taking long-term anticonvulsants
• Patients with malabsorption syndromes.
Key points
Vitamin toxicities
• Vitamin A – gastro-intestinal upsets, headache (raised
intracranial pressure), desquamation, hepatotoxicity
and teratogenicity.
• Nicotinic acid – flushing, vasodilatation and
hepatotoxicity.
• Vitamin C – hyperoxaluria and oxalate stones.
• Vitamin D – hypercalcaemia.
ESSENTIAL FATTY ACIDS
Several naturally occurring unsaturated fatty acids are essential
dietary components. Linoleic and linolenic acids occur in
vegetable oils and nuts, arachidonic acid occurs in meat, and
longer-chain fatty acids (eicosapentanoic acid and docosahexanoic
acid) are found in cold-water oily fish. Humans synthesize
arachidonic acid (C20:4) from shorter-chain (C18:2)
essential fatty acids by chain elongation and desaturation.
Arachidonic acid is present in the lipid component of cell membranes
throughout the body. It is esterified on the 2-position
of glycerol in membrane phospholipids and is liberated by
phospholipases when cells are injured or stimulated. Free
arachidonic acid is the precursor of the 2-series of prostaglandins,
thromboxanes, the 4-series of leukotrienes and epoxyeicosatetraenoic
acids which are important in many physiologic and
pathologic states, including control of inflammation, haemostasis
and vascular tone. Deficiency states have been described in
patients receiving long-term parenteral nutrition and are prevented
by the use of lipid emulsions.
TRACE ELEMENTS
A total of 13 nutritionally essential trace elements are recognized,
namely fluorine, silicon, vanadium, chromium, manganese,
iron, cobalt, nickel, copper, zinc, selenium, tin and
iodine. These are required in the human body at 0.01% of
body weight. Most of them are highly reactive chemically and
one or more of these elements is present at the active site of
many enzymes. They are present in small but adequate amounts
in a normal diet, but evidence is accumulating that in addition
to iron, cobalt (Chapter 49) and iodine (Chapter 38), zinc,