The Antioxidant of Antioxidants – How Alpha-Lipoic Acid Benefits Fertility, Metabolism and More
What is Alpha-Lipoic Acid (ALA)?
Alpha-lipoic acid (ALA) is an organosulfur compound produced in the mitochondria from octanoic acid (caprylic acid). In the body, only the R-form of ALA is naturally produced, and it is always bound to proteins as a cofactor. While best known as a versatile antioxidant in both fat- and water-soluble tissues, ALA also supports energy metabolism within the mitochondria as a coenzyme in the citric acid cycle (CAC).1
Preclinical studies show that ALA boosts skeletal muscle glucose uptake, and indirectly increases the NAD+/NADH ratio which enhances sirtuin 1 (SIRT1) activity and can promote AMPK activation. These effects can support improved mitochondrial function, insulin sensitivity and weight management in metabolic disorders.2,3
ALA may also support brain energy metabolism, reduce inflammation and protect against oxidative stress (including via Nrf2 activation) in age-associated and neuroinflammatory conditions (preclinical evidence).4-9
Free ALA levels in the body are normally very low, but supplementation can transiently raise circulating levels, enabling systemic antioxidant and redox-balancing effects.1
Figure 1. Antioxidant and Other Activities of Alpha-Lipoic Acid (ALA)10
NB: ALA and dihydrolipoic acid (DHLA) are a redox pair – ALA is the oxidised form and DHLA is the reduced form. They scavenge several reactive oxygen species (ROS). DHLA also regenerates vitamin C and vitamin E, and helps maintain intracellular glutathione.1 When vitamin E scavenges a peroxyl radical, it forms a vitamin E radical that can be regenerated by vitamin C, ubiquinol and glutathione. DHLA can reduce all of these antioxidants and is itself regenerated by cellular reductases. Together, ALA and DHLA play crucial roles in the body’s antioxidant network.10
What Are the Key Clinical Applications of ALA?
Clinical applications of ALA are predominantly cardiometabolic and neuroinflammatory in nature, aligning with activities highlighted in Figure 1. Evidence shows that ALA is of benefit in the following conditions, with doses ranging from 20 to 1800 mg/day (though most commonly prescribed at a dose of 600 mg/day):
- Female11-15 and male fertility,16 including in women undergoing IVF
- Cardiometabolic parameters17-22 and diseases including PCOS,23,24 NAFLD,25 gestational diabetes,26-28 diabetes29 and its complications (diabetic nephropathy,30,31 neuropathy32,33 and hypertension),34 obesity,35-38 and post stroke39,40
- Chronic kidney disease41
- Psychiatric and neurological disorders including schizophrenia,42 Alzheimer’s disease,42,43 multiple sclerosis,44 and migraine prophylaxis45,46
- Sensory dysfunction (smell,47 taste48 and noise-induced hearing loss)49 and vision in dry age-related macular degeneration50
- Pain disorders (burning mouth syndrome,51-53 carpal tunnel syndrome,54-56 chronic neck pain,57 chronic lumbosacral radicular pain from herniated disc,58 radicular syndrome from herniated disc,59 sciatic pain from herniated disc,60 chemotherapy-induced neuropathy,61,62 chronic pelvic pain,63-65 and idiopathic pain)66
* Some IV administration trials included in meta-analyses; ALA combined with other nutrients or drugs in some trials and meta-analyses
Co-Prescribing with ALA
Some studies have combined ALA with other nutrients, including inositol,12,13,15,24 several vitamins (B group vitamins, vitamin C and vitamin E), acetyl-L-carnitine, coenzyme Q10 (CoQ10), polyunsaturated fatty acids (PUFAs), resveratrol, N-acetylcysteine (NAC), selenium, creatine, phosphatidylserine, Ginkgo, curcumin,21,25,42,56,67-71 and palmitoylethanolamide (PEA),65,67,72 among others. Theoretically, Siberian Ginseng may also be worth co-supplementing in cases of sensory dysfunction73 and diabetic neuropathy.74
Recall, from the description below Figure 1, that ALA is an important component of the body’s antioxidant network, providing key context for critically evaluating the potential benefits of co-prescribing it alongside other antioxidants or cofactors, such as NAC and selenium to support glutathione activity.
ALA Safety Considerations
ALA is well tolerated when used appropriately at typical doses.1,75,76
ALA has been associated with rare cases of toxicity when ingested in high amounts, particularly when taken over a short period of time; avoid high doses.77-81
*For more information refer to the Eagle Clinical Alpha-Lipoic Acid Monograph or contact Clinical Support at clinicalsupport@integria.com.
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