What Is Alpha-Lipoic Acid? Other Names: Acetate Replacing Factor, Acide Thioctique, Thioctic Acid

What is Alpha-Lipoic Acid?

This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Alpha-lipoic acid (ALA) is a naturally occurring compound that plays a crucial role in mitochondrial dehydrogenase reactions. It has garnered significant attention due to its potent antioxidant properties and potential therapeutic benefits in various medical conditions. This article explores the biochemical functions, therapeutic applications, and safety profile of alpha-lipoic acid. Other names include: A-Lipoic Acid, Acetate Replacing Factor, Acide Alpha-Lipoïque, Acide Alpha-Lipoïque R, Acide DL-Alpha-Lipoïque,Acide Lipoïque, Acide Thioctique, Acide 1,2-dithiolane-3-pentanoïque, Acide 1,2-dithiolane-3-valérique, Acide 5 Valérique (1,2-dithiolan-3-yl), Acide 6,8-dithiooctanoïque, Acide 6,8-Thioctique, Acido Alfa Lipoico, ALA, Biletan, DHLA, Dihydrolipoic Acid, Extrait d’acide Alpha-Lipoïque, Lipoic Acid, Lipoicin, R-ALA, R-Alpha-Lipoic Acid, (+-)-1,2-Dithiolane-3-Pentanoic Acid, (R)-Dithiolane-3-Pentanoic Acid,R, S-Alpha Lipoic Acid, (R)-Lipoic Acid, R-Lipoic Acid, RS-Alpha-Lipoic Acid, S-Alpha-Lipoic Acid, S-Lipoic Acid, Sodium-R-Lipoate, Thioctacid, Thioctan,Thioctic Acid.

Biochemical Functions

Alpha-lipoic acid is essential for mitochondrial oxidative metabolism, acting as a cofactor for mitochondrial respiratory enzymes. It participates in the oxidative decarboxylation of pyruvate and alpha-ketoglutarate, which are critical steps in cellular energy production1 4. ALA exists in both oxidized and reduced forms, with the reduced form, dihydrolipoic acid, exhibiting strong antioxidant properties. It can neutralize reactive oxygen species (ROS) such as superoxide radicals, hydroxyl radicals, and peroxyl radicals, thereby protecting cells from oxidative damage1 6.

Antioxidant Properties

ALA’s antioxidant capabilities extend beyond direct scavenging of ROS. It interacts with other antioxidants like vitamin C and glutathione, which can recycle vitamin E, enhancing the overall antioxidant defense system of the body1 9. Additionally, ALA has been shown to modulate the activity of transcription factors such as NF-kappa B, which plays a role in the cellular response to oxidative stress9.

Therapeutic Applications of Alpha-Lipoic Acid

Diabetes and Insulin Sensitivity

ALA has been extensively studied for its potential benefits in diabetes management. It enhances glucose transport and utilization, improving insulin sensitivity in patients with type-2 diabetes. Clinical studies have demonstrated that both intravenous and oral administration of ALA can significantly increase insulin-stimulated glucose disposal5 7. Moreover, ALA has shown promise in alleviating symptoms of diabetic polyneuropathy, a common complication of diabetes8.

Weight Management

Research indicates that ALA may aid in weight management. A randomized, double-blind, placebo-controlled trial found that obese individuals who took 1800 mg of ALA daily experienced modest weight loss compared to those who received a placebo2. This suggests that ALA could be considered as an adjunctive therapy for obesity.

Liver Health

ALA has therapeutic potential in liver diseases, particularly those involving oxidative stress. It has been used successfully in treating conditions such as alcohol-induced liver damage, mushroom poisoning, and metal intoxication6. Recent studies have also highlighted its role in improving insulin resistance and diabetic polyneuropathy, further supporting its use in liver-related metabolic disorders6.

Neuropathic Pain and Gynecological Conditions

ALA’s antioxidant and anti-inflammatory properties make it beneficial in treating neuropathic pain and certain gynecological conditions. It has been used in combination with other compounds to manage conditions like polycystic ovary syndrome (PCOS) and endometriosis4. Additionally, ALA supplementation during pregnancy has shown potential in preventing diabetic embryopathy and premature rupture of fetal membranes4.

Safety Profile

A systematic review and meta-analysis of randomized placebo-controlled clinical studies have confirmed that ALA supplementation is generally safe. The analysis, which included data from 71 clinical studies, found no significant increase in the risk of adverse events associated with ALA supplementation3. Common side effects, such as urticaria and itching, were mild and transient2.

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Adverse Effects of Alpha-Lipoic Acid

Gastrointestinal and Skin Reactions

Common adverse effects include nausea, vomiting, dizziness, cutaneous rash, and gastrointestinal issues such as urticaria and itching sensation1 3 4.

Hypoglycemia and Hypotension

ALA can cause hypoglycemia and hypotension, particularly at higher doses (800 mg/day and 1200 mg/day)1.

Serious Adverse Events

Serious adverse events reported include insulin autoimmune syndrome, angioedema, and anaphylactic shock. These events are rare but significant4.

General Safety Profile

Meta-analyses and systematic reviews indicate that ALA supplementation is generally safe and not associated with an increased risk of adverse events in most populations, including those with metabolic diseases, cardiovascular conditions, and during pregnancy5 6 9.

Early Onset of Adverse Events

Most adverse events occur within the first 30 days of ALA use, suggesting that initial monitoring is crucial4.

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How has Alpha-Lipoic Acid Improved Patient Outcomes?

Improvement in Diabetic Polyneuropathy Symptoms

ALA significantly reduces sensory symptoms in diabetic sensorimotor peripheral neuropathy (DSPN), showing dose-dependent improvements in total symptom scores and global satisfaction2 4.

Long-term ALA treatment (4 years) improves neuropathic impairments and prevents progression, especially in patients with higher disease burden and controlled cardiovascular risk factors5.

Enhanced Glycemic Control and Insulin Sensitivity

ALA supplementation significantly decreases fasting glucose, insulin levels, insulin resistance, and HbA1c in patients with metabolic diseases7.

Oral ALA treatment improves insulin sensitivity in type-2 diabetes patients, as evidenced by increased insulin-stimulated glucose disposal10.

Reduction in Oxidative Stress

ALA decreases oxidative stress markers, even in diabetic patients with poor glycemic control and albuminuria, indicating its robust antioxidant effects9.

Cardiovascular and Hemodialysis Benefits

In diabetic patients on hemodialysis, ALA reduces inflammation, oxidative stress, and erythropoietin resistance, while improving glycemic control and cardiovascular risk markers1.

Post-Surgical Recovery in Carpal Tunnel Syndrome

ALA improves clinical and neurophysiologic outcomes in patients undergoing surgery for idiopathic carpal tunnel syndrome, with significant improvements noted even before surgery3.

Potential Benefits in Acute Ischemic Stroke

ALA use in diabetic patients with acute ischemic stroke treated with thrombolysis is associated with better functional outcomes, lower risks of early neurological deterioration, and hemorrhagic transformation8.

Possible Role in COVID-19 Management

Preliminary data suggest that ALA may reduce organ failure scores and 30-day all-cause mortality in critically ill COVID-19 patients, though larger studies are needed to confirm these findings6.

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Alpha-Lipoic Acid Mechanisms of Action

Antioxidant Activity and Radical Scavenging

ALA and its reduced form, dihydrolipoic acid, directly scavenge reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), protecting cells from oxidative damage1 2 7 8.

ALA recycles other antioxidants such as vitamin C, vitamin E, and glutathione, enhancing the overall antioxidant defense system1 2 7 8.

Modulation of Transcription Factors

ALA influences the activity of several transcription factors, including NF-kappa B, which plays a role in inflammatory responses and oxidative stress1 2 8.

It also modulates the transcription factors SREBP-1, FoxO1, and Nrf2 via the SIRT1/LKB1/AMPK pathway, contributing to lipid metabolism and antioxidant responses4.

Insulin Receptor Activation

ALA activates the insulin receptor/PI3-kinase/Akt pathway, providing cytoprotective effects and reducing apoptosis in hepatocytes. This action is partly due to ALA’s direct binding to the insulin receptor tyrosine kinase domain3.

Metabolic Effects

ALA has been shown to activate AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptors (PPARs), which are involved in metabolic regulation, weight loss, and improving insulin sensitivity4 5.

Pro-oxidant Effects

While ALA generally acts as an antioxidant, it can exhibit pro-oxidant properties under certain conditions, such as in non-diabetic kidneys, where it may increase oxidative stress and renal dysfunction6 7 8.

Anti-cancer Activity

ALA induces cell cycle arrest and apoptosis in cancer cells, such as MCF-7 human breast cancer cells, by reducing ROS levels and modulating the PI3-K/Akt signaling pathway and apoptotic proteins10.

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Common Complaints Associated with Alpha-Lipoic Acid Use

Mild and Transient Skin Reactions

Urticaria (hives) and itching sensation are common but generally mild and transient adverse events associated with ALA use1.

General Safety Profile

A systematic review and meta-analysis of 71 clinical studies found that ALA supplementation is not associated with an increased risk of any treatment-emergent adverse events, indicating a generally safe profile across various populations, including those with cardiovascular disease, diabetes, and neurological disorders2.

Adverse Events in Diabetic Neuropathy Treatment

In a study involving diabetic patients with symptomatic polyneuropathy, the rates of adverse events were not significantly different between the ALA and placebo groups, suggesting that ALA does not cause significant adverse reactions in this context3.

Severe Reactions in Children

A case report highlighted a severe adverse reaction in a 14-month-old child who ingested an unknown amount of ALA, leading to status epilepticus (a serious condition involving continuous seizures). This indicates that ALA can cause severe side effects in children, particularly when ingested in large amounts4.

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Disclaimer

The content presented in this blog is generated by Consensus, an AI-powered academic search engine, and is based on publicly available scientific literature. While every effort is made to provide accurate, up-to-date, and well-researched information, the content is intended for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before making any decisions regarding medical conditions, treatments, or medications. The AI system’s analysis may not cover all perspectives, emerging research, or individual cases, and it is not a substitute for professional expertise. Neither the blog publisher nor the developers of the AI-powered search engine are responsible for any actions taken based on the information provided in this content. Use of this information is at your own risk. Citations to the original scientific studies are included for reference, but these studies should be reviewed in full and interpreted with the guidance of a healthcare or research professional.

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