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NCBI Bookshelf. Hiep Nguyen ; Vikas Gupta. Authors Hiep Nguyen 1 ; Vikas Gupta 2. Alpha-lipoic acid is a medication used in managing and treating chronic diseases associated with oxidative stress such as diabetic neuropathy and slowing down the onset of metabolic syndrome by acting as an antioxidant. This activity outlines the indications, mechanism of action, contraindications, and other key elements of alpha-lipoic acid supplements in the clinical setting related to the essential points needed by members of an interprofessional team in the management treatment of oxidative stress-related to chronic metabolic disorders.
Objectives: Identify the indications for alpha-lipoic acid supplementation. Describe the pathophysiology of alpha-lipoic acid toxicity. Explain the importance of monitoring for patients on alpha-lipoic acid supplementation. Summarize the risks associated with initiating alpha-lipoic acid supplementation and summarize key patient counseling points. Alpha-Lipoic acid ALA is a caprylic acid-derived anti-oxidant. It is synthesized in the mitochondria and plays an essential role as a cofactor, assisting in the enzymatic nutrient breakdown. ALA has recently gained a reputation as an antioxidant.
In its reduced form, dihydrolipoate reacts and neutralizes ROS, such as superoxide radicals, singlet oxygen, and hydroxyl radicals. Thus, it is extremely beneficial in several oxidative-stress associated conditions such as ischemia-reperfusion or radiation injury. Secondly, numerous studies have strongly supported the role of ALA in treating diabetic neuropathy. It does so by enhancing nitric oxide-mediated endothelium-dependent vasodilation, thus improving microcirculation in patients with diabetic polyneuropathy.
Also, ALA possesses an excellent iron-chelation property. The thiol groups in ALA are responsible for chelating irons. By increasing the glutathione levels inside the cells, ALA and dihydrolipoate excrete various toxins, especially toxic metals in the body. Lipoic acid preferentially binds to Zn, Pb, and Cu. So far, ALA has the strongest evidence of its therapeutic effect in diabetic neuropathy and oxidative-stress conditions. According to the FDA, ALA is reported to be safe and effective, and that there are promising uses that can be explored in future studies.
ALA's chemical reactivity is dictated by its dithiolane ring. Both are capable of scavenging a variety of ROS. DHLA is a potent antioxidant that can neutralize free radicals without becoming one in the process. Furthermore, ALA simultaneously regenerates other antioxidant factors such as vitamin C and E, subsequently increasing glutathione synthesis.
ALA expresses its anti-inflammatory effect by inhibiting I Kappa B kinase, a converging enzyme for the activation of NF-kB, thus suppressing the activation of other inflammatory cytokines. ALA is available in the form of oral supplementation and intravenous injection.
Studies postulate promising therapeutic properties in several conditions, including type 1 and 2 diabetes mellitus DM , neuropathy, and ischemic-perfusion injury. Oral: Data demonstrates daily oral supplementation of mg of ALA over the course of 3 months maintains and improves functional vision in type 1 and type 2 DM patients, respectively. Intravenous injection: The study shows evidence for IV treatment of daily mg in improving positive neuropathic symptoms and neuropathic deficits.
ALA is considered a safe supplementation without any side affect. One study supports the safety of the drug in which an adult can take up to mg without experiencing any harmful side effects. An ALA study in on six rhesus monkeys showed that excess lethal dose in primate would cause hepatic necrosis.
This le the researchers to conclude that exceptionally high doses of intravenous ALA can produce the same symptoms that smaller doses prevent. Thus far, few studies have analyzed the safety of ALA supplementation in pregnant women or children. Therefore, these populations are advised to consult with their healthcare providers when considering taking ALA. There were very few studies on the contraindications in using ALA. Also, one should stop using ALA immediately if an allergic reaction occurs, such as skin rash, nausea, or vomiting.
There is not any established contraindication of ALA in pregnant women and infants. Even though ALA intoxication is extremely rare, close monitoring is necessary for children who are around diabetic patients, as most of the reported ALA intoxication cases belong to children ingesting ALA by accident. Also, a case of ALA intoxication was reported in which the patient attempted to commit suicide. Thus, it is worth monitoring the use of ALA in people who has suicidal thoughts or psychological issues. There is no established therapeutic index of ALA in humans. However, studies show that safety dosage has been defined in animals.
In animal studies, high levels of ALA were reported to cause hepatotoxicity, apathy, confusion, and hypokinesis. ALA is considered a safe drug, generally. However, there is no reported safety dose in children. There was a case in which a month-old was admitted to the emergency room with vomiting, lethargy, involuntary movements for several hours.
He was believed to have accidentally ingesting four pills of mg ALA. He was later diagnosed with status epilepticus because of prolonged convulsions for half an hour. In the follow-up, he was treated with midazolam infusion up to 0. In the following few days, he became conscious without further seizure recurrence. In the last two decades, there are very few reported cases of ALA toxicity in humans.
Most of these cases occur in children and are treatable. ALA intoxication cases are rare and happen mostly in the pediatric population. Most of the cases were accidental; therefore, better communication is needed between healthcare providers to provide the appropriate dosage and monitoring information to patients, especially to diabetic patients with children. Also, patients should always consult with their primary doctor before taking the ALA supplementation. ALA is a generally safe supplement that can be purchased over the counter. Primary care physicians may act as frontline and provide proper dosage and safety information to the patients.
Other specialists and health care professionals monitor and treat any adverse events of the supplement. Appropriate cooperation between all the health professionals is essential to ensure the patient receives the most effective care and optimal benefits from ALA supplementation. This book is distributed under the terms of the Creative Commons Attribution 4.
Turn recording back on. National Center for Biotechnology Information , U. StatPearls [Internet]. Search term. Affiliations 1 Nova Southeastern University. Continuing Education Activity Alpha-lipoic acid is a medication used in managing and treating chronic diseases associated with oxidative stress such as diabetic neuropathy and slowing down the onset of metabolic syndrome by acting as an antioxidant.
Mechanism of Action ALA's chemical reactivity is dictated by its dithiolane ring. Administration ALA is available in the form of oral supplementation and intravenous injection. Adverse Effects ALA is considered a safe supplementation without any side affect. Contraindications There were very few studies on the contraindications in using ALA.
Monitoring Even though ALA intoxication is extremely rare, close monitoring is necessary for children who are around diabetic patients, as most of the reported ALA intoxication cases belong to children ingesting ALA by accident. Toxicity ALA is considered a safe drug, generally. Comment on this article. References 1. Packer L, Cadenas E. Lipoic acid: energy metabolism and redox regulation of transcription and cell aling.
J Clin Biochem Nutr. Diabetes and alpha lipoic Acid. Front Pharmacol. Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells. Neurosci Lett.Recommended dose alpha lipoic acid
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