Lipoic Acid

Lipoic Acid Common Names

Lipoic acid | R-Lipoic acid | alpha-Lipoic acid | α-Lipoic acid | ALA | Thioctic acid

Top Benefits of Lipoic Acid

  • Supports cellular energy creation*
  • Supports mitochondrial efficiency*
  • Supports healthy metabolism*
  • Supports antioxidant defenses*
  • Supports circadian rhythms*

What Is Lipoic Acid?

Lipoic acid is an important mitochondrial compound, because it’s used in helper molecules (i.e., enzymes) for the metabolic processes that convert food energy into cellular energy (ATP). Lipoic acid is often characterized as an antioxidant, though in living systems it plays a larger role supporting the body’s own antioxidant defenses, upregulating important cellular defense molecules like glutathione and preserving Nrf2 function. It’s also involved in cellular signaling, especially with AMPK, considered a master cellular energy sensor and regulator. Lipoic acid was originally discovered in the 1930’s and has been used as a nutrient since the late 1950’s. While lipoic acid is found in many foods, amounts obtained in the diet are very low. The richest food sources are organ meats (e.g., kidney, liver) and vegetables such as spinach and broccoli. Mitochondria can make lipoic acid starting from a medium chain fat called caprylic acid (also called  octanoic acid), which is found in some foods (e.g., milk, coconut) and can also be made in the body. Many animals and human studies report functional benefits when diets are supplemented with extra lipoic acid. This suggests there are circumstances where the amount made inside cells and supplied by foods in the diet are insufficient to optimize health. 

Neurohacker’s Lipoic Acid Sourcing

We use Bio-Enhanced®, Stabilized R-Lipoic Acid (sodium R-alpha-lipoic acid), the most bioavailable and potent form of lipoic acid.

Created by GeroNova Research, Inc., a leader in lipoic acid research. 

Most lipoic acid in vitamins is a 50/50 mix of the R-(natural) and S-(unnatural) enantiomers. Only the R-lipoic acid is found in our body and used as a cofactor in human enzymes.

Supplementation with Bio-Enhanced®, Stabilized R-Lipoic Acid results in much higher lipoic acid blood levels compared to lipoic acid.[1]

Bio-Enhanced is a registered trademark of GeroNova Research, Inc.

Lipoic Acid Dosing Principles and Rationale

Lipoic acid is generally considered to be dose-dependent (see Neurohacker Dosing Principles) in the range it’s commonly dosed. Higher supplemental doses are typically used when it is given as a single nutrient, while much lower doses are used when it is given in combination with other mitochondrial nutrients (e.g., CoQ10, PQQ, L-carnitine). Lower doses can also be used when using the more bioavailable stabilized R-lipoic acid or when combining lipoic acid with other ingredients that act as bioenhancers, such as piperine from black pepper.

Lipoic Acid Key Mechanisms

 Mitochondrial biogenesis

  • Upregulates mitochondrial mass[2]
  • Upregulates mitochondrial DNA (mtDNA)[2]
  • Upregulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α)[2–5]
  • Upregulates nuclear transcription factors of mitochondrial biogenesis (nuclear respiratory factor 1 [NRF1], NRF2, mitochondrial transcription factor [TFAM])[2, 3, 5–7]
  • Induces brown-like features in adipose tissue[2]

Mitochondrial structure and function

  • Cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase[8]
  • Upregulates the NAD+ pool and the NAD+ : NADH ratio[6,9]
  • Protects from complex I-V inhibition[5,7,10]
  • Promotes oxidative phosphorylation and ATP production[4,5,7]
  • Promotes fatty acid β-oxidation[9,11]
  • Supports membrane potential[7,12]

Signaling pathways

  • Upregulates AMPK signaling[4–7,9,11,13–18]
  • Upregulates liver kinase B1 (LKB1) signaling[6,18]
  • Upregulates FOXO1 activity[6]
  • Upregulates peroxisome proliferator-activated receptor alpha (PPARα) signaling[4,19]
  • Upregulates the cAMP/CREB signaling pathway[3]


  • Supports healthy insulin sensitivity[11,15,20–25]
  • Upregulates GLUT4 activity[13,22,26]
  • Downregulates fat accumulation and blood/liver lipid levels[6,14,15]
  • Upregulates adiponectin levels[15]

Antioxidant defenses

  • Upregulates antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPx])[3,20,23,27]
  • Replenishes glutathione (GSH) levels[7,12,22,27]
  • Downregulates oxidative stress and reactive oxygen species production[12,23,27,28]

Protective effects

  • Neuroprotective against neurotoxic agents[7,27,29,30]
  • Protects vascular function[3]
  • Protects cardiac structure[17]
  • Supports healthy blood pressure[23]
  • Protects liver function[10]

Healthy aging and longevity

  • Upregulates SIRT-1 activity[2,5,6,9]
  • Upregulates SIRT-3 activity[10]
  • Upregulates uncoupling protein 1 (UCP1) activity[2]
  • Stimulates telomerase activity / protects from telomere dysfunction[3]
  • Protects DNA from damage[3]
  • Downregulates mTOR signaling[4,13]

Circadian rhythms

  • Influences genes associated with governing circadian rhythms in the liver[31]
  • Modulates the expression patterns of circadian clock proteins in the liver[19]


  • Coenzyme Q10 – support of mitochondrial function[32–35]
  • Creatine – support of mitochondrial function[32–35]
  • Inositol – insulin sensitivity[36]
  • Piperine and curcumin  –  additive effects when combined[37]


[1] D. A. Carlson, A. R. Smith, S. J. Fischer, K. L. Young, L. Packer, Altern. Med. Rev. 12, 343–351 (2007).
[2] M. Fernández-Galilea et al., Biochim. Biophys. Acta. 1851, 273–281 (2015).
[3] S. Xiong, N. Patrushev, F. Forouzandeh, L. Hilenski, R. W. Alexander, Cell Rep. 12, 1391–1399 (2015).
[4] Z. Li, C. M. Dungan, B. Carrier, T. C. Rideout, D. L. Williamson, Lipids. 49, 1193–1201 (2014).
[5] T. Jiang, F. Yin, J. Yao, R. D. Brinton, E. Cadenas, Aging Cell. 12, 1021–1031 (2013).
[6] Y. Yang et al., J. Nutr. Biochem. 25, 1207–1217 (2014).
[7] G. Song et al., Food Funct. 8, 4657–4667 (2017).
[8] A. Solmonson, R. J. DeBerardinis, J. Biol. Chem. 293, 7522–7530 (2018).
[9] W.-L. Chen, C.-H. Kang, S.-G. Wang, H.-M. Lee, Diabetologia. 55, 1824–1835 (2012).
[10] Z. Liu et al., Biochimie. 116, 52–60 (2015).
[11] W. J. Lee et al., Biochem. Biophys. Res. Commun. 332, 885–891 (2005).
[12] T. M. Hagen et al., FASEB J. 13, 411–418 (1999).
[13] Y. Wang, X. Li, Y. Guo, L. Chan, X. Guan, Metabolism. 59, 967–976 (2010).
[14] K.-G. Park et al., Hepatology. 48, 1477–1486 (2008).
[15] P. L. Prieto-Hontoria, P. Pérez-Matute, M. Fernández-Galilea, J. Alfredo Martínez, M. J. Moreno-Aliaga, Eur. J. Nutr. 52, 779–787 (2013).
[16] M. Fernández-Galilea et al., Obesity . 22, 2210–2215 (2014).
[17] J. E. Lee et al., Cardiovasc. Diabetol. 11, 111 (2012).
[18] P.-Y. Cheng, Y.-M. Lee, M.-T. Chung, Y.-C. Shih, M.-H. Yen, Am. J. Hypertens. 25, 152–158 (2012).
[19] D. Keith et al., Biochem. Biophys. Res. Commun. 450, 324–329 (2014).
[20] H. Ansar, Z. Mazloom, F. Kazemi, N. Hejazi, Saudi Med. J. 32, 584–588 (2011).
[21] S. Jacob et al., Free Radical Biology and Medicine. 27, 309–314 (1999).
[22] A. Rudich, A. Tirosh, R. Potashnik, M. Khamaisi, N. Bashan, Diabetologia. 42, 949–957 (1999).
[23] A. El Midaoui, J. de Champlain, Hypertension. 39, 303–307 (2002).
[24] S. Jacob et al., Free Radic. Biol. Med. 27, 309–314 (1999).
[25] S. Jacob et al., Diabetes. 45, 1024–1029 (1996).
[26] M. Khamaisi et al., Metabolism. 46, 763–768 (1997).
[27] A. O. Abdel-Zaher, R. H. Abdel-Hady, W. M. Abdel Moneim, S. Y. Salim, Exp. Toxicol. Pathol. 63, 161–165 (2011).
[28] B. A. Maddux et al., Diabetes. 50, 404–410 (2001).
[29] O. Tirosh, C. K. Sen, S. Roy, M. S. Kobayashi, L. Packer, Free Radic. Biol. Med. 26, 1418–1426 (1999).
[30] J. T. Greenamyre, M. Garcia-Osuna, J. G. Greene, Neurosci. Lett. 171, 17–20 (1994).
[31] L. A. Finlay et al., Am. J. Physiol. Regul. Integr. Comp. Physiol. 302, R587–97 (2012).
[32] M. C. Rodriguez et al., Muscle Nerve. 35, 235–242 (2007).
[33] S. Savitha, K. Sivarajan, D. Haripriya, V. Kokilavani, C. Panneerselvam, Clin. Nutr. 24, 794–800 (2005).
[34] A. Abadi et al., Supplementation with α-Lipoic Acid, CoQ10, and Vitamin E Augments Running Performance and Mitochondrial Function in Female Mice. PLoS ONE. 8 (2013), p. e60722.
[35] S. Silvestri et al., J. Clin. Biochem. Nutr. 57, 21–26 (2015).
[36] I. Capasso et al., Trials. 14, 273 (2013).
[37] F. Di Pierro, R. Settembre, J. Pain Res. 6, 497–503 (2013).

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.