Biotin supplementation

Prenatal and postnatal diagnoses can be made by enzyme assay of cultured amniocytes, fibroblasts or white blood cells. Treatment remains symptomatic. Sodium bicarbonate is necessary to correct the acidosis. Aspartic acid supplementation will improve the systemic condition but has no effect on the neurological disturbances. Biotin supplementation is of no value. 

Acquired biotin deficiency is extremely rare but may occur in special conditions such as long-term parenteral nutrition without biotin supplementation, short bowel syndrome and after excessive intake of raw egg white, which contains the potent bio-tin-binding protein avidin. The main symptoms are alopecia and skin abnormalities which resolve after administration of biotin [2, 30]. 

Children with any of the isolated carboxylase deficiencies do not improve with biotin supplementation, whereas those with multiple carboxylase deficiency do. A trial of biotin is often expedient and useful in discriminating between the isolated carboxylase deficiencies and the multiple carboxylase deficiencies. Isolated carboxylase deficiencies can be definitively confirmed by demonstrating deficient enzyme activity of one of three mitochondrial carboxylases in extracts of peripheral blood leukocytes (prior to biotin therapy) or cultured fibroblasts, whereas the activities of the other two carboxylases are normal. 

The organic acid analysis in the urine of this child was consistent with biotin deficiency or multiple carboxylase deficiency. Biotin deficiency usually can be excluded unless there is a history of dietary indiscretion, such as consuming a diet containing raw eggs or few biotin-containing foods, or there is a history of prolonged parenteral hyperalimentation without biotin supplementation. Low serum biotin concentrations can be useful in differentiating... 

The mainstay of therapy in biotinidase deficiency is biotin supplementation. To date, all symptomatic children with biotinidase deficiency have improved after treatment with 5 to 10 mg of biotin per day. Biotin appears to be required in the free form as opposed to the bound form. This is based on the findings of two children who were fed yeast as a form of therapy. Neither improved because essentially all of the biotin in yeast is protein bound, and these children could not recycle the biotin. These children, however, did improve when treated with free biotin. Treatment with biotin is essential and sufficient to prevent or resolve the symptoms. It is not necessary to treat children with biotinidase deficiency with protein-restricted diets as it is in some of the isolated carboxylase deficiencies because with biotin therapy all the carboxylase activities are normal. Symptoms of biotinidase deficiency are preventable if patients are diagnosed and treated at birth or before symptoms occur. 

Reddi A, DeAngelis B, Frank O, Lasker N, and Baker H (1988) Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice. Life Sciences 42, 1323-30. 

Velazjt)uez,. A., Teran, M., Baez, A., Gutierrez, J., and Rodriguez, R. (1995). Biotin supplementation affects lymphocyte carboxylases and plasma biotin in severe protein-energy malnutrition. Am. /. CJiti. j jdr. 61, 3S5-39L... 

Supplements. Biotin is available in multivitamin and mnltivitamin/multimineral products as well as in single ingredient products. The major benefit of biotin as a dietary supplement is in strengthening hair and nails. Some skin disorders, such as cradle cap, improve with biotin supplements. Biotin has also been used to combat premature graying of hair, though it is likely to be useful only for those with a low biotin level. Biotin has been used for people in weight-loss programs to help them metabolize fat more efficiently. 

A negative correlation between deficient biotin status and blood lipid concentrations was found in rats (Marshall et al. 1976) as well as in humans (Marshall et al. 1980). A decrease in plasma lipids was observed in human healthy volunteers within 30 min of absorption of 100 mg of biotin infusion. It was shown that oral biotin supplementation affected plasma lipid concentrations. The administration of 5 mg/day of biotin decreased hypercholesterolemia in atherosclerosis and hyperlipidemia patients (Dukusova and Krivoruchenko 1972). A 15 mg/day treatment by biotin for 28 days decreased hypertriglyceridemia of subjects whose triacylglycerol concentrations were more than 25% above the normal of 1.8mmol/L (Baez-Saldana 2004). 

Although frank biotin deficiency is rarely seen, it has been described in patients receiving parenteral nutrition without biotin supplementation and in those with biotinidase deficiency (Zempleni and Mock 1999c). Consuming large amounts of raw egg-white could also provoke biotin deficiency, decreasing biotin absorption tightly bound to avidin. 

Arslan, M., Vurucu, S., Balamtekin, N., Unay, B., Akin, R., Kurt, I., and Ozcan, O., 2009. The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid. Brain cfe Development. 31 405 10. 

Wiedmann S, Eudy JD, and Zempleni J. Biotin supplementation increases expression of genes encoding interferon-gamma, interleukin-ip and 3-methylcotonyl-CoA carboxylase and decreases expression of the gene encoding interleukin-4 in human peripheral blood mononuclear cells. J. Nutr, 133 716-719 (2003). 

Singer GM and Geshas J. The effect of chromium picolinate and biotin supplementation... 

Revilla-Monsalve C, Zendejas-Ruiz I, Islas-Andrade S, Baez-Saldana A, Palomino-Garibay MA, Hernandez-Quiroz PM, and Fernandez-Mejia C. Biotin supplementation reduces plasma triacyl glycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia. Biomed. Pharmacother. 60 182-185 (2006). 

GRIFFIN, J. B., RODRIGUEZ-MELENDEZ, R., DODE, L., WUYTACK, R, ZEMPLENL J. (2006) Biotin supplementation decreases the expression of the SERCA3 gene (ATP2A3) in Jurkat cells, thus, triggering unfolded protein response. J. Nutr. Biochem., 17,272-281. 

ZEMPLENI, J., HELM, R. M., MOCK, D. M. (2001) in vivo biotin supplementation at a pharmacologic dose decreases proliferation rates of human peripheral blood mononuclear cells and cytokine release. J. Nutr., 131, 1479-1484. 

Three months later, at a regular out-patient visit, it was decided to cease the biotin supplements. Within a week the abnormal organic acids were detected in his urine again and he was treated with varying doses of biotin until the organicaciduria ceased. This was achieved at an intake of 150 Jg/day (compared with the reference intake of 10—20 ig/day for an infant under 2 years old). 

Lymphocyte PCC activity is an early and sensitive indicator of marginal biotin deficiency. In 11 of 11 subjects, lymphocyte PCC activity decreased to abnormal values by day 28 of egg-white feeding and returned to normal in 8 of 11 within 3 weeks of resuming a general diet with or without biotin supplement. 

Data providing an accurate estimate of the dietary and parenteral biotin requirements for infants, children, and adults are lacking. However, recommendations for biotin supplementation have been formulated for oral and parenteral intake for preterm infants, term infants, children, and adults (Table 2). 

The fact that normal humans have a requirement for biotin has been clearly documented in two situations prolonged consumption of raw egg white and parenteral nutrition without biotin supplementation in patients with short bowel syndrome and other causes of malabsorption. Based on lymphocyte carboxylase activities and plasma biotin levels, some children with severe protein-energy malnutrition are biotin deficient. Investigators have speculated that the effects of biotin deficiency may be responsible for part of the clinical syndrome of protein-energy malnutrition. 

Further enzymological studies on the condition have been provided by Bartlett et al. (1980), who described a 4-year-old girl with mild metabolic acidosis and who excreted grossly increased concentrations of 3-hydroxy-isovaleric acid and 3-methylcrotonylglycine in her urine. She was responsive to biotin therapy (oral, 5 mg day ) and studies on her cultured skin fibroblasts showed deficient activities of propionyl-CoA carboxylase and of 3-methyl-crotonyl-CoA carboxylase. Studies in vivo showed that the latter enzyme was stimulated by biotin supplementation of the medium to a much greater degree than the other mitochondrial carboxylase enzymes. 

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