Vitamin A retinol

Vitamins are substances that are essential for normal metabolism and must be chiefly supplied in the diet.

Humans cannot synthesise vitamins in the body except some vitamin D in the skin and nicotinamide from tryptophan. Lack of a particular vitamin may lead to a specific deficiency syndrome. This may be primary (inadequate diet), or secondary, due to failure of absorption (intestinal abnormality or chronic diarrhoea), or to increased metabolic need (growth, pregnancy, lactation, hyperthyroidism).

Vitamin deficiencies are commonly multiple, and complex clinical pictures occur. There are numerous single and multivitamin preparations to provide prophylaxis and therapy.

It has often been suggested, but never proved,

Vitamin A is a generic term embracing substances having the biological actions of retinol and related substances (which are called retinoids). The principal functions of retinol are to:

• sustain normal epithelia

• form retinal photochemicals

• enhance immune functions

• protect against infections and probably some cancers.

Deficiency of retinol leads to metaplasia and hyperkeratosis throughout the body. This metaplasia is reminiscent of the early stage of transformation of normal tissue to cancer.

Retinol and derivatives are used in doses above those needed for nutrition, i.e. pharmacotherapy, in dyskeratotic skin diseases (psoriasis, acne) and in leukaemia.

Tretinoin is retinoic acid. It is used in acne by topical application, see page 313, and orally to induce remission in promyelocytic leukaemia.

Isotretinoin is a retinoic acid isomer (t\ 20 h). It is used orally in acne (see p. 313). It is effective in preventing second primary tumours in patients who have been treated for squamous cell carcinoma of the head and neck.

Acitretin is a retinoic acid derivative (iV2 48 h). It is used orally for psoriasis, see p. 313.

Retinol itself is used in prevention and treatment of deficiency (tV2 7-14 d).

Adverse effects

Toxic effects occur with prolonged high intake (in children 25 000-500 000IU daily). A diagnostic sign of chronic poisoning is the presence of painful tender swellings on the long bones. Anorexia, skin lesions, hair loss, hepatosplenomegaly, papilledema, bleeding and general malaise also occur. Vitamin A is very cumulative (it is stored in liver and fat) and effects take weeks to wear off. Most cases of vitamin A poisoning have been due to mothers administering large amounts of fish-liver oils to their children in the belief that it was good for them.

Chronic overdose also causes an increased liability of biological membranes and of the outer layer of the skin to peel. An extreme example of this is the case of the hungry Antarctic explorer who in 1913 ate the liver of his husky sledge dogs. His feet felt sore and the sight of my feet gave me quite a shock, for the thickened skin of the soles had separated in each case as a complete layer ... I did what appeared to be the best thing under the circumstances: smeared the new skin with lanoline ... and with bandages bound the skin soles back in place.1

Vitamin A and its derivatives are teratogenic at

1 Shearman J C 1978 Vitamin A and Sir Douglas Mawson. British Medical Journal 1: 283.

above physiological doses, i.e. with pharmacotherapy (for precautions, see use in acne and psoriasis, p. 313). Misguided pregnant health enthusiasts may take enough self-prescribed supplements to hazard a fetus. The Teratology Society advises that supplements should not exceed 8000 IU (2400 micrograms) per day.

Acute overdose: Travellers have been made ill by eating the livers of Arctic carnivores:

Eskimos never eat polar-bear liver, knowing it to be toxic, and husky dogs, with instinctive wisdom, also avoid it. Those who pooh-pooh the Eskimos' fears of the husky dogs' instincts and are tempted to enjoy a man's portion of polar-bear liver — appetites get sharp near the North Pole — will consume anything up to 10 000 000 IU of vitamin A (normal daily requirement is 5000 IU). This is too much of a good thing, and the diner will probably soon find himself drowsy then overcome by headache and vomiting, and finally losing the outer layer of his skin.2

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