by Allison Sayre, MSN, WHNP-BC
Alpha-lipoic acid (ALA), is a naturally occurring compound that has gained increasing attention for its multifaceted support of metabolic wellness, cellular energy, and nerve health.* ALA plays a vital role in mitochondrial function, oxidative balance, and glucose metabolism, which are areas deeply intertwined with overall vitality and longevity.* In this article we will explore the mechanisms of action and potential benefits of ALA in relation to metabolic wellness, body composition, and nerve health.*
What is Alpha-Lipoic Acid?
Alpha-lipoic acid is synthesized in the body from the medium-chain fatty acid octanoic acid, and is a component of a mitochondrial protein complex necessary for synthesis and degradation of the amino acid glycine.* ALA also acts as a cofactor for several enzymes including pyruvate dehydrogenase complex (PDC) and alpha-ketoglutarate dehydrogenase complex (KDC), two mitochondrial enzymes that are key to cellular glucose metabolism and energy production.*[1]
In addition to its metabolic functions, ALA has been shown to balance cytokine activity, support the body’s natural defenses against oxidative stress, help regenerate antioxidants such as vitamins C and E, enhance intracellular glutathione levels, and chelate certain heavy metals, all of which are functions that support oxidative balance and cellular resilience.* ALA has also demonstrated the ability to modulate key cellular pathways including NF-kB, which is involved in reparative responses, and Nrf2, which affects antioxidant defense.*[1]
So, where can we find this powerful compound? Well, small amounts of ALA are found in foods like spinach, broccoli, and organ meats, although the bioavailability of dietary ALA is somewhat unreliable, with dietary intake alone often being insufficient to significantly elevate plasma levels.* By contrast, oral supplementation has been shown to offer a more effective route to achieving physiologically meaningful concentrations in the bloodstream.*[2]
Effect of Lipoic Acid on Metabolic Health*
One key component of metabolic balance involves the body’s cellular responsiveness to insulin, a hormone that helps regulate blood sugar. Simply put, when cells respond efficiently to insulin, the body is better able to maintain stable blood sugar levels and support metabolic balance. This contributes to healthy energy production, reduces oxidative stress, and promotes optimal function across multiple organ systems.* As a result, nutrients and compounds that support normal and healthy insulin sensitivity and help maintain a healthy oxidative balance are of growing interest for supporting long-term metabolic health.*
Among these, ALA stands out for its ability to support healthy cellular metabolism.* By promoting the activity and translocation of GLUT4, an insulin-regulated glucose transporter, ALA helps facilitate more efficient glucose uptake into muscle and adipose tissue.* As a result, ALA assists in maintaining healthy blood sugar levels within normal limits and promoting balanced energy metabolism.*[4] Additionally, ALA supplementation may support healthy lipid profiles, including total and LDL cholesterol within normal limits.*[5]
Benefits of Alpha-Lipoic Acid to Body Composition*
We all know that a healthy body composition is an important factor in overall metabolic health and cardiovascular well-being.
A systematic review and meta-analysis of ALA supplementation:
· Included 12 placebo-controlled clinical trials
· Published in the journal Clinical Nutrition
· Dosage ranged from 300-1800 mg per day
· N=784
· Those participants with body mass index (BMI) was associated with a statistically significant reduction in body mass when compared to placebo.*[6]
So, what is this effect attributed to? Well, ALA appears to also influence central appetite-regulation mechanisms by acting on hypothalamic AMPK activity and supporting leptin signaling, both of which contribute to satiety cues.*[6] ALA has also been shown to help modulate enzymes like lipoprotein lipase, which regulate fat storage and mobilization.*[6]
Benefits of Alpha-Lipoic Acid to Nerve Health*
Healthy metabolic function supports nerve integrity and comfort, particularly in the lower extremities. By promoting balanced oxidative status and cellular energy, the body is better equipped to maintain sensation, strength, and overall neurological health.* Because of its ability to support the body’s natural defenses against oxidative stress, ALA has been studied as a supplement to potentially maintain the health of nerves and metabolic health.* In fact, ALA supports healthy nerve conduction velocity, improves nerve signal amplitude, and supports overall nerve function.*[7]
In a clinical investigation, 45 adults were supplemented with oral alpha-lipoic acid (ALA) at a dosage of 600 mg, three times daily, 30 minutes after a meal, for four weeks. Participants who received ALA supplementation (600 mg daily) reported notable improvements in comfort and quality of life, reflected by an average 60% improvement on a standardized wellness rating scale. Those who experienced positive results were then randomly assigned to either continue or discontinue ALA for an additional 16 weeks. Among those who continued, overall well-being scores improved by an additional 32%, and their reliance on other support measures was 50% lower compared to those who discontinued supplementation.*[7]
An earlier multicenter, randomized, double-blind, placebo-controlled study of 181 participants receiving various daily dosages of ALA (600, 1200, or 1800 mg) for five weeks, demonstrated significant improvements in subjective assessments and overall quality-of-life measures.* Notably, the 600 mg per day dose was found to be just as effective as higher doses in this trial.*[8]
Summary and Practical Recommendations
Alpha-lipoic acid offers a wide range of potential benefits for supporting metabolic health, promoting healthy body composition, and maintaining nerve function in the presence of oxidative and glycemic stress.* Because it serves as a mitochondrial cofactor and has the ability to support antioxidant activity, ALA stands out as a versatile nutrient in the toolkit of metabolic wellness.* With a growing body of evidence and a well-characterized safety profile, alpha-lipoic acid continues to be a valuable ally for those seeking to support overall well-being and cellular resilience in the modern age.*
For best results, ALA supplements are often recommended to be taken on an empty stomach, as concurrent food intake may theoretically reduce absorption. Dosages of 300–600 mg per day are commonly used in research, though individualized recommendations should be guided by a healthcare practitioner, available evidence, and individual needs.
The information provided is for educational purposes only. Consult your physician or healthcare practitioner if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
Allison Sayre, MSN, WHNP specializes in women's health and functional medicine, blending both traditional and integrative approaches. With over 17 years of experience, she has empowered women to reclaim their health through personalized nutrition and supplementation, hormone balancing, and lifestyle modifications. She received her Bachelor of Science from Mount Carmel College of Nursing and her Master of Science from the University of Cincinnati. She has been a certified women’s health nurse practitioner since 2014 and has continued her education and training in functional medicine from both the Institute for Functional Medicine as well as the American Academy of Anti-Aging Medicine