High doses of ALA without the Biotin can interfere with some of the biotin-controlled enzyme pathways, creating for all effects and purposes a biotin deficiency.
PMID: 9278559 [PubMed - indexed for MEDLINE]
J Neurochem. 1992 Apr;58(4):1460-3. Related Articles, Links
Biotin transport in primary culture of astrocytes: effect of biotin
deficiency.
Rodriguez-Pombo P, Ugarte M.
Departamento de Biologia Molecular, Facultad de Ciencias,
Universidad Autonoma de Madrid, Spain.
The uptake of radioactive biotin has been studied in glial cell
cultures from dissociated cerebral hemispheres of newborn rats. We
describe saturable kinetics for the biotin uptake at biotin
concentrations of less than 60 nM and linear at greater than 60 nM. The
uptake appeared temperature sensitive, Na+ independent, nonsensitive to
valinomycin, and not affected by metabolic inhibitors such as sodium
fluoride or azide. Lipoic acid and biocytin were effective in inhibiting
the biotin uptake. These findings are consistent with biotin uptake by
the primary culture of astrocytes as a process of facilitated diffusion.
Moreover, biotin uptake in astrocytes grown in biotin-restricted
conditions was significantly higher compared with the control. This
increase appeared mediated through a pronounced increase (10-fold) in
the Vmax of the biotin uptake without any change in the apparent Km.
PMID: 1548480 [PubMed - indexed for MEDLINE]
What the study means is simply that if you take lipoic acid, be sure to
supplement with biotin.
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J Nutr. 1997 Sep;127(9):1776-81. Related Articles, Links
Lipoic acid reduces the activities of biotin-dependent carboxylases
in rat liver.
Zempleni J, Trusty TA, Mock DM.
Department of Pediatrics, University of Arkansas for Medical
Sciences and the Arkansas Children's Hospital Research Institute, Little
Rock, AR 72202, USA.
In the past, lipoic acid has been administered to patients and test
animals as therapy for diabetic neuropathy and various intoxications.
Lipoic acid and the vitamin biotin have structural similarities. We
sought to determine whether the chronic administration of lipoic acid
affects the activities of biotin-dependent carboxylases. For 28 d, rats
received daily intraperitoneal injections of one of the following: 1) a
small dose of lipoic acid [4.3 micromol/( kg.d)]; 2) a large dose of
lipoic acid [15.6 micromol/(kg.d)]; or 3) a large dose of lipoic acid
plus biotin [15.6 and 2.0 micromol/(kg.d), respectively]. Another group
received n-hexanoic acid [14.5 micromol/(kg.d)], which has structural
similarities to lipoic acid and biotin and thus served as a control for
the specificity of lipoic acid. A fifth group received
phosphatidylcholine in saline injections and served as the vehicle
control. The rat livers were assayed for the activities of acetyl-CoA
carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and
beta-methylcrotonyl-CoA carboxylase. Urine was analyzed for lipoic acid;
serum was analyzed for indicators of liver damage and metabolic
aberrations. The mean activities of pyruvate carboxylase and
beta-methylcrotonyl-CoA carboxylase were 28-36% lower in the lipoic
acid-treated rats compared with vehicle controls (P < 0.05). Rats
treated with lipoic acid plus biotin had normal carboxylase activities.
Carboxylase activities in livers of n-hexanoic acid-treated rats were
normal despite some evidence of liver injury. Propionyl-CoA carboxylase
and acetyl-CoA carboxylase were not significantly affected by
administration of lipoic acid. This study provides evidence consistent
with the hypothesis that chronic administration of lipoic acid lowers
the activities of pyruvate carboxylase and beta-methylcrotonyl-CoA
carboxylase in vivo by competing with biotin.