In 1916, Bateman showed the toxicity of a diet that contained large amounts of crude eggs in rats. In 1931 Gyorgyi hypothezied the role of a vitamin deficiency in this disease and named it " the disease of crude egg white ". This vitamin is called vitamin H.

Later, in yeast Wieldlers discovered growth factors that he called bios or biotin. Vitamin H, bios and biotine are the same product, theis compound will be named " vitamin B8 " and it belongs to the water-soluble vitamins. The disease of crude egg white is caused by by a glycoprotein : avidin – which binds strongly biotine. Avidin is thermolabile.

Biotin is a cofactor of carboxylases that are implicated in cellular metabolism. In 1981 Munich described biotin-carboxylase failures, inherited metabolic diseases, and their improvement by large supplements of biotin.

Biotin is a cofactor of carboxylases that catalyse CO2 binding on different substrates. These reactions are called carboxylation and transcarboxylation.

In humans, 4 biotin-dependant carboxylases are known, they act in glucose, fatty acids, and certains amino-acid metabolism

These are principally:
Pyruvate carboxylase,
Acetyl-COA carboxylase,
Propionyl-COA carboxylase,
b -methylcrotonyl-COA carboxylase.

Normal diet covers daily biotin needs. Adults must absorb 100 to 300 µg biotin per day, and children should absorb 50 to 90 µg biotin per day. However, a biotin deficiency may occur in persons who eat crude eggs, or in parenteral feeding.

Dry yeast contains 180 to 400 µg biotin per 100 g. Liver contains about 80 µg biotin, eggs 20 mg per 100 g. Musrooms, beans, meat, fish and bread contain less biotin. Milk, cheese, vegetables and fruit only contain a little biotin (<5 µg/100g). Boiling foods in water distroys up to 40% biotin.

After a 3-4 weeks period of unsufficient intakes, astheny and anorexia appear. Sometimes, a slim weight loss also occurs. They are accompanied by :

Skin signs : skin lesions, onyxis and perionyxis, candida albicans

Psychiatric signs : depression, drowsiness, hallucinations, sensitivity troubles and muscle pain

Digestive signs : nausea, vomiting, liver steatosis

Biological signs : metabolic acidosis (acidocetosis, hyperlactatemia, hyper ammonemia) and organic aciduria.

In children a psychological and motor delay is observed, along with hypotonia, ataxia, and convultions. Metabolic acidosis may cause coma.

If unsupplemented, parenteral nutrition may cause biotin deficiency as parenteral fluids contains no vitamin B8. Deficiency signs appear after 6 month to 3 years in adults, faster in children ( 3-6 monthes). Daily 30µg/kg supplements prevent any deficiency.

Inherited metabolic diseases : the first biotin-carboxylase deficiency was described in 1979 by Cowan and Wara. It is the most frequent cause of inborn metabolic acidosis, it can be cured by large per-os biotin supplements.

Rarely, other causes may trigger a biotin deficiency :
Absorption of large quantities of crude eggs. Indeed, avidin binds strongly biotin and thus prevents it from being absorbed in gut.
Breast feeding when milk is not rich enough in biotin.
Haemodialysis : brain and nerve failures have been described, they can be reversed by biotin
Fifth day fit : low hepatic biotin concentrations have been found (Johnson 1980)
Global nutritional unsufficiency.

Low biotin status

Sometimes, biotin levels are low, but without clinical expression :
Chronic antiepileptic treatments : biotin absorption is depressed by competition with antiepileptic drugs, and biotinidase binding is altered.
Alcoolism
Gut diseases, older persons, burns

Biotin status is not altered in vegetarians. (Lombard, 1989)

Biotin is not toxic, even at large dosages.

Diagnosis

Deficiency diagnosis is based on :
Global signs, shin signs, psychiatric and digestive signs
Biological signs : metabolic acidosis and aciduria.

Haemodialysis, parenteral nutrition, inborn errors of metabolism represent most at-risk situations of biotin deficiency.

Diagnosis of biotin deficiency will be confirmed by a blood measurement, after an overnight fasting and before any supplementation.