Adverse Effects of High doses of Intravenous Alpha Lipoic Acid on Liver Mitochondria

Abstract

Alpha lipoic acid (ALA, thioctic acid), among other actions, is an essential coenzyme in the conversion of pyruvate to acetyl co-enzyme A. Therefore, it is necessary for the production of energy for aerobic organisms. Scientists have found that it can be used medically to help regenerate liver tissue, reverse the complications of diabetes mellitus, slow or stop the growth of cancer cells, and chelate heavy metals, among other actions. In this article, the authors describe the cellular mitochondrial damage from excessively high doses of this beneficial agent.

α-Lipoic Acid Protects Against Ischemia-Reperfusion Injury in Simultaneous Kidney-Pancreas Transplantation

“…Nausea 38 and itching have been reported with high doses (1 200-1 800 mg) of ALA. 39 However, recently, adverse effects on liver mitochondria have been reported with high IV doses. 40 This high dose (90-100 mg/kg) extremely exceeded the dose used in our study (600 mg). In our study, we detected no side effects, such as those described in the studies mentioned above.…”

Alpha-lipoic acid treatment of acetaminophen-induced rat liver damage

“…Ç akatay (2006) added that this pro-oxidant effect is determined by the model of oxidant stress and the physiological status of the body. Another explanation for disparate fi ndings has been suggested (Moini et al 2002a, Bhatti et al 2005, Vigil et al 2014. When large amounts of ALA come in contact with diatomic oxygen in the mitochondrion, they form superoxide anions that react with the unsaturated double bonds in lipids of the mitochondrial membranes, which causes lipid oxidation and liver necrosis.…”

Ascorbic acid prolongs the viability and stability of isolated perfused lungs: A mechanistic study using 31P and hyperpolarized 13C nuclear magnetic resonance

“…Although there is a debate about glutathione uptake by the lung [90], the significant increase in the alanine ratio and decrease in the lactate ratio are consistent with the previous studies [91], and suggest that GSH was taken up by the lung cells that are actively metabolizing pyruvate [92].. ALA is a coenzyme of the PDHc, and an effective antioxidant against ROS and associated mitochondrial dysfunction [86,93]. Although the decrease in the bicarbonate ratio in the presence of 2mM ALA was not significant (figure 5a), the increase in lactate ratio in ALA-perfused lungs shows that sufficient ALA was taken up to influence metabolism as well [94]. These studies suggest that the primary means by which ascorbic acid increases PDHc activity is not related to a general ROSscavenging or antioxidant effect.…”