Alpha Lipoic Acid (ALA)

• Antioxidant
• Diabetes control*
• Weight loss

*approved for treatment of diabetic neuropathies in Germany²

Antioxidant: ALA acts as an antioxidant through free radical scavenging in vitro.^{3; 4} However, since ALA only transiently accumulates in tissues in vivo, the significance of direct free radical scavenging activity by ALA in vivo is questionable.⁵ It is more likely that ALA acts as an indirect antioxidant in vivo that induces or maintains endogenous antioxidant levels.⁵ ALA can increase glutathione levels within cells.^{6; 7} ALA can also regenerate reduced vitamin C and vitamin E from their respective oxidized vitamin forms. A pro-oxidant effect of ALA has also been described in experimental studies when relatively high concentrations of ALA are achieved. However, this pro-oxidant effect is believed to occur at levels typically higher than those observed in human studies using oral or intravenous infusion of ALA.⁸

Diabetic control: Studies that investigated the effects of ALA on diabetes control related to its role in inhibiting glycation reactions and the antioxidant mechanisms of action.

Weight loss: ALA may promote body weight and fat mass reduction via decreasing food intake and enhancing energy expenditure, possibly via suppression of hypothalamic AMP-activated protein kinase (AMPK) activity.^{9; 10}

Sporting/exercise applications: Limited studies in humans show improvements in systemic markers of oxidative stress and antioxidant capacity following muscle-damaging exercise with short-term ALA supplementation¹¹. Evidence from animal studies shows inconclusive effects on skeletal muscle oxidative stress, antioxidant enzymes, mitochondrial biogenesis, and endurance performance.¹¹ Some studies conducted in humans have investigated markers of muscle damage during recovery following an intense muscle-damaging exercise bout with supplementation with ALA (600 mg/day) for 8-10 days.^{12; 13} Zembron-Lacny et al.¹³ reported significantly lower creatine kinase following combined submaximal endurance exercise and a muscle damaging eccentric downhill treadmill run, while Zembron-Lacny et al.¹² reported no significant effect of ALA supplementation on either creatine kinase or lactate dehydrogenase levels following muscle damaging eccentric resistance exercise.

Diabetes: ALA has been found to reduce micro- and macro-vascular diabetic complications in rodents^{14; 15} and improve neuropathic pain in rodents¹⁶ and humans.² ALA has also been shown to improve insulin sensitivity in rodents¹ and humans¹⁷ with diabetes.

Weight loss: a recent meta-analysis of RCTs found a small but significant mean weight loss of 1.27 (95% CI -2.29 to -0.25) kg in clinical patients across studies using doses of 300-1800 mg LA per day for between 8-52 weeks.¹⁸

There is an overall lack of studies in humans investigating sporting/exercise-related outcomes, and no conclusive evidence to currently support ALA supplementation for benefits on endurance performance or muscle recovery from intense exercise.

Studies in diabetes are promising, however evidence is mainly limited to rodent data and small, short-term studies in patients with diabetes.

Evidence for weight loss benefits suggest only small weight loss benefits that are arguably not of clinical significance for overweight/obese individuals.

Lacking evidence for improved health or performance in athlete populations.

1. Streeper RS, Henriksen EJ, Jacob S, Hokama JY, Fogt DL, Tritschler HJ. (1997). Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. The American journal of physiology, 273, 185-191.
2. Mijnhout GS, Kollen BJ, Alkhalaf A, Kleefstra N, Bilo HJ. (2012). Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. International journal of endocrinology.
3. Packer L, Kraemer K, Rimbach G. (2001). Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition, 17, 888-895.
4. Trujillo M, Radi R. (2002). Peroxynitrite reaction with the reduced and the oxidized forms of lipoic acid: new insights into the reaction of peroxynitrite with thiols. Archives of biochemistry and biophysics, 397, 91-98.
5. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. (2009). Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochimica et biophysica acta, 1790, 1149-1160.
6. Busse E, Zimmer G, Schopohl B, Kornhuber B. (1992). Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittel- Forschung, 42, 829-831.
7. Tibullo D, Li Volti G, Giallongo C, Grasso S, Tomassoni D, Anfuso CD, Lupo G, Amenta F, Avola R, Bramanti V. (2017). Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential. Inflammation research: official journal of the European Histamine Research Society, 66, 947-959.
8. Gomes MB, Negrato CA. (2014). Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetology & metabolic syndrome, 6, 80.
9. Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Alfredo Martínez J, Moreno-Aliaga MJ. (2013). Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats. European journal of nutrition, 52, 779-787.
10. Wang Y, Li X, Guo Y, Chan L, Guan X. (2010). Alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphateactivated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice. Metabolism: clinical and experimental, 59, 967-976.
11. Mason SA, Trewin AJ, Parker L, Wadley GD. (2020). Antioxidant supplements and endurance exercise: Current evidence and mechanistic insights. Redox biology, 35, 101471.
12. Zembron-Lacny A, Slowinska-Lisowska M, Szygula Z, Witkowski K, Stefaniak T, Dziubek W. (2009). Assessment of the antioxidant effectiveness of alpha-lipoic acid in healthy men exposed to muscle-damaging exercise. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 60, 139-143.
13. Zembron-Lacny A, Gajewski M, Naczk M, Dziewiecka H, Siatkowski IJJoP, (2013). Physical activity and alpha-lipoic acid modulate inflammatory response through changes in thiol redox status. Biochemistry, 69, 397-404.
14. Lin J, Bierhaus A, Bugert P, Dietrich N, Feng Y, Vom Hagen F, Nawroth P, Brownlee M, Hammes HP. (2006). Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy. Diabetologi, 49, 1089-1096.
15. Yi X, Maeda N. (206). Alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed highfat/low-cholesterol diet. Diabetes, 55, 2238-2244.
16. Lee WY, Orestes P, Latham J, Naik AK, Nelson MT, Vitko I, Perez-Reyes E, Jevtovic-Todorovic V, Todorovic SM. (2009). Molecular mechanisms of lipoic acid modulation of T-type calcium channels in pain pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience, 29, 9500-9509.
17. Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K. (1999). Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free radical biology & medicine, 27, 309-314.
18. Kucukgoncu S, Zhou E, Lucas KB, Tek C. (2017). Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta analysis of randomized controlled trials. Obes Rev, 18, 594-601.

1. Carlson DA, Smith AR, Fischer SJ, Young KL, Packer L. (2007). The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)- lipoate to healthy human subjects. Alternative medicine review : a journal of clinical therapeutic, 12, 343-351.
2. Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D. (2005). Lipoic acid in multiple sclerosis: a pilot study. Multiple sclerosis, 11, 159-165.
3. Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R. (1999). Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-mon