Unlocking Longevity Benefits: Alpha-Lipoic Acid vs. R-Lipoic Acid

In a nutshell

  1. Alpha-lipoic acid (ALA) is a powerful antioxidant with several potential health benefits, including improved mitochondrial function, blood sugar control, cardiovascular health, and neuroprotection.
  2. The primary difference between ALA d and R-lipoic acid is their molecular composition. ALA is comprised of both R-lipoic acid and S-lipoic acid. While the latter is synthetically produced and not readily absorbable by the body, R-lipoic acid is highly bioavailable and responsible for all of the health benefits associated with alpha-lipoic acid.
  3. Therefore, R-lipoic acid is considered more potent and better absorbed by the body than ALA. So, taking pure R-lipoic acid as a supplement can be more effective.

What is Alpha-Lipoic Acid?

Alpha-lipoic acid, commonly known as ALA or lipoic acid, is an organic sulfur compound that originates from caprylic acid. While the human body naturally produces alpha-lipoic acid in the mitochondria, it can also be obtained from various food sources.

ALA that is produced within the body is bound to proteins and functions as a cofactor for numerous essential mitochondrial multienzyme complexes that play a role in energy generation and amino acid metabolism.1 Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 2018 May 18;293(20):7522-7530. doi: 10.1074/jbc.TM117.000259. Epub 2017 Nov 30. PubMed Source

What is the difference between R-Lipoic Acid and Alpha-Lipoic Acid?

ALA consists of two forms of lipoic acid, R form, and S form. These forms are identical in terms of chemical composition but have a mirrored structure.2 Salehi, Bahare et al. “Insights on the Use of α-Lipoic Acid for Therapeutic Purposes.” Biomolecules vol. 9,8 356. 9 Aug. 2019. PubMed Source The R form of lipoic acid is a naturally occurring compound that can be found in various foods and is also produced by the body. In contrast, the S form is synthetic and not naturally present in the body. It’s worth noting that the R form is responsible for all of the health benefits that alpha lipoic acid provides to the body.

Although the human body produces ALA in small amounts, its amount is insufficient to meet the cell’s energy needs. Therefore, we primarily obtain ALA from our diet or supplementation.

Food is a natural source of R form lipoic acid. Foods that are rich in lipoic acid are red meat, organ meats (such as liver, kidneys, and heart), vegetables (especially leafy greens like spinach, broccoli, and Brussels sprouts), and some yeast (brewer’s yeast). Some lipoic acid can be found in fruits but in much smaller amounts. We can also get ALA from supplements.

Health Benefits of Alpha-Lipoic Acid

Antioxidant and anti-inflammatory effects

ALA is a powerful antioxidant that has been shown to improve mitochondrial function, which can help to slow down the aging process and reduce the risk of age-related diseases. 3Hong YS, Jacobia SJ, Packer L, Patel MS. The inhibitory effects of lipoic compounds on mammalian pyruvate dehydrogenase complex and its catalytic components. Free Radic Biol Med. 1999 Mar;26(5-6):685-94. PubMed Source 4 Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann N Y Acad Sci. 2002 Apr;959:133-66. doi: 10.1111/j.1749-6632.2002.tb02090.x. PubMed Source

ALA also has anti-inflammatory effects.5 Moura FA, de Andrade KQ, dos Santos JC, Goulart MO. Lipoic Acid: its antioxidant and anti-inflammatory role and clinical applications. Curr Top Med Chem. 2015;15(5):458-83. PubMed Source It can help to reduce inflammation by decreasing the production of pro-inflammatory cytokines, inhibiting the activation of transcription factors that promote inflammation, and scavenging free radicals that can cause oxidative stress and inflammation. Studies have suggested that ALA may be beneficial in reducing inflammation associated with various chronic diseases such as diabetes, arthritis, and cardiovascular disease.

Reduces weight and regulates BMI

One study that analyzed results from many other studies on ALA supplementation showed that prolonged use reduces body weight, BMI, and waist circumference.6 Vajdi M, Abbasalizad Farhangi M. Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose-response meta-analysis of randomised placebo-controlled clinical trials. Int J Clin Pract. 2020 Jun;74(6):e13493. doi: 10.1111/ijcp.13493. Epub 2020 Mar 26 PubMed Source

Improves glucose metabolism

ALA improves insulin sensitivity and increases glucose uptake in insulin-resistant cells because it can mimic insulin’s properties.7 Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, Kim MS, Kim SW, Lee KU, Park JY. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun. 2005 Jul 8;332(3):885-91. PubMed Source

ALA is widely used as a natural method for relieving nerve pain in diabetes.8Ibrahimpasic K. Alpha lipoic acid and glycaemic control in diabetic neuropathies at type 2 diabetes treatment. Med Arch. 2013;67(1):7-9. PubMed Source It has this effect due to its ability to lower blood glucose, protecting from nerve damage.

Improves cognitive performance

Healthcare providers may recommend ALA supplements to provide additional support in safeguarding their patients from neuron damage, memory loss, motor impairment, and cognitive dysfunction, due to ALA’s potent antioxidant properties.

Studies show that supplementation with ALA can improve learning and memory in Alzheimer’s disease.9 Quinn JF, Bussiere JR, Hammond RS, Montine TJ, Henson E, Jones RE, Stackman RW Jr. Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Neurobiol Aging. 2007 Feb;28(2):213-25. doi: 10.1016/j.neurobiolaging.2005.12.014. Epub 2006 Jan 31. PubMed Source

Improves cardiovascular health

Due to its antioxidant properties, ALA demonstrates a strong cardioprotective effect.10 Geleijnse JM, de Goede J, Brouwer IA. Alpha-linolenic acid: is it essential to cardiovascular health? Curr Atheroscler Rep. 2010 Nov;12(6):359-67. doi: 10.1007/s11883-010-0137-0. PubMed Source In fact, it has been shown that increased intake of ALA is associated with a 10% lower risk of cardiovascular diseases and a 20% lower risk of fatal ischaemic heart disease.11Sala-Vila A, Fleming J, Kris-Etherton P, Ros E. Impact of α-Linolenic Acid, the Vegetable ω-3 Fatty Acid, on Cardiovascular Disease and Cognition. Adv Nutr. 2022 Oct 2;13(5):1584-1602. PubMed Source ALA’s anti-inflammatory and antioxidant effects help prevent the development of atherosclerosis and hypertension.

Role of Alpha-Lipoic Acid in Longevity

Due to the ALA’s ability to reduce the progression of Alzheimer’s disease and improve diabetes, it is often considered a powerful anti-aging substance. However, studies on its ability to prolong lifespan showed controversial results.12 Farr, Susan A et al. “Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice.” Journal of Alzheimer’s disease : JAD vol. 32,2 (2012): 447-55. PubMed Source 13Lee, Cheol-Koo et al. “The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice.” Free radical biology & medicine vol. 36,8 (2004): 1043-57.  PubMed Source

Some studies show that ALA can extend the lifespan of different animals like fruit flies, worms and mice. 14Du G, Qiao Y, Zhuo Z, Zhou J, Li X, Liu Z, Li Y, Chen H. Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction. EMBO Rep. 2020 Aug 5;21(8):e49583. doi: 10.15252/embr.201949583. PubMed Source 15 Lemon JA, Boreham DR, Rollo CD. A complex dietary supplement extends longevity of mice. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):275-9.  PubMed Source 16 Brown MK, Evans JL, Luo Y. Beneficial effects of natural antioxidants EGCG and alpha-lipoic acid on life span and age-dependent behavioral declines in Caenorhabditis elegans. Pharmacol Biochem Behav. 2006 Nov;85(3):620-8. PubMed Source  It can restore mitochondrial function in cells, reversing their age. On the other hand, a study in genetically modified mice, showed that ALA shortened their lifespan.17Farr SA, Price TO, Banks WA, Ercal N, Morley JE. Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. J Alzheimers Dis. 2012;32(2):447-55. PubMed Source

Currently, no sufficient, well-conducted studies in humans demonstrate that ALA extends lifespan, probably due to its low bioavailability. Until recently, most ALA products on the market contained the unnatural S form because R form is very unstable and difficult to produce. So, most of the clinical research conducted at ALA and its health benefits were carried out using the blend of R and S forms.

Nowadays, R forms of ALA also became available, although at a higher price compared to ALA. But this makes us believe that improved formulations can increase ALA absorption and bioavailability leading to new promising results.

How to Take Alpha-Lipoic Acid and What Form is Better?

According to a study, the bioavailability of ALA significantly decreases when consumed with food.18 Gleiter CH, Schug BS, Hermann R, Elze M, Blume HH, Gundert-Remy U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol. 1996;50(6):513-4. PubMed Source As a result, it has been advised that ALA should be consumed at least two hours after eating. Alternatively, it can be taken 30 mins before the meal.

However, most longevity experts agree that the best time to take ALA would be in the morning on an empty stomach.19 DAVID SINCLAIR “Alpha Lipoic Acid For Mitochondrial Health” | Dr David Sinclair Interview Clips. URL This is because the acidic pH of the stomach in the morning is favorable for ALA absorption, and it doesn’t compete with other nutrients for absorption.

It is important to remember that supplements usually contain a 50/50 blend of the R and S forms. And since the S form possesses relatively low biological activity, only the R form will be absorbed by the body. So, supplementing with a pure R form of lipoic acid could yield more benefits.

Recap and final thoughts

The main difference between alpha-lipoic acid and R-lipoic acid is their molecular structure. Alpha-lipoic acid is a mixture of R-lipoic acid and S-lipoic acid. While S-lipoic acid is synthesized and cannot be easily absorbed by the body, R-lipoic acid is easily bioavailable and is responsible for all health benefits of alpha-lipoic acid. So supplementing with pure R-lipoic acid can be more efficient.

To learn about other vitamins and minerals that can benefit health and improve longevity, please see 7 Anti-Aging Vitamins for Health and Longevity and Top 6 Minerals for Vitality and Longevity.

References

  • 1
    Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 2018 May 18;293(20):7522-7530. doi: 10.1074/jbc.TM117.000259. Epub 2017 Nov 30. PubMed Source
  • 2
    Salehi, Bahare et al. “Insights on the Use of α-Lipoic Acid for Therapeutic Purposes.” Biomolecules vol. 9,8 356. 9 Aug. 2019. PubMed Source
  • 3
    Hong YS, Jacobia SJ, Packer L, Patel MS. The inhibitory effects of lipoic compounds on mammalian pyruvate dehydrogenase complex and its catalytic components. Free Radic Biol Med. 1999 Mar;26(5-6):685-94. PubMed Source
  • 4
    Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann N Y Acad Sci. 2002 Apr;959:133-66. doi: 10.1111/j.1749-6632.2002.tb02090.x. PubMed Source
  • 5
    Moura FA, de Andrade KQ, dos Santos JC, Goulart MO. Lipoic Acid: its antioxidant and anti-inflammatory role and clinical applications. Curr Top Med Chem. 2015;15(5):458-83. PubMed Source
  • 6
    Vajdi M, Abbasalizad Farhangi M. Alpha-lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose-response meta-analysis of randomised placebo-controlled clinical trials. Int J Clin Pract. 2020 Jun;74(6):e13493. doi: 10.1111/ijcp.13493. Epub 2020 Mar 26 PubMed Source
  • 7
    Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, Kim MS, Kim SW, Lee KU, Park JY. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun. 2005 Jul 8;332(3):885-91. PubMed Source
  • 8
    Ibrahimpasic K. Alpha lipoic acid and glycaemic control in diabetic neuropathies at type 2 diabetes treatment. Med Arch. 2013;67(1):7-9. PubMed Source
  • 9
    Quinn JF, Bussiere JR, Hammond RS, Montine TJ, Henson E, Jones RE, Stackman RW Jr. Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Neurobiol Aging. 2007 Feb;28(2):213-25. doi: 10.1016/j.neurobiolaging.2005.12.014. Epub 2006 Jan 31. PubMed Source
  • 10
    Geleijnse JM, de Goede J, Brouwer IA. Alpha-linolenic acid: is it essential to cardiovascular health? Curr Atheroscler Rep. 2010 Nov;12(6):359-67. doi: 10.1007/s11883-010-0137-0. PubMed Source
  • 11
    Sala-Vila A, Fleming J, Kris-Etherton P, Ros E. Impact of α-Linolenic Acid, the Vegetable ω-3 Fatty Acid, on Cardiovascular Disease and Cognition. Adv Nutr. 2022 Oct 2;13(5):1584-1602. PubMed Source
  • 12
    Farr, Susan A et al. “Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice.” Journal of Alzheimer’s disease : JAD vol. 32,2 (2012): 447-55. PubMed Source
  • 13
    Lee, Cheol-Koo et al. “The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice.” Free radical biology & medicine vol. 36,8 (2004): 1043-57.  PubMed Source
  • 14
    Du G, Qiao Y, Zhuo Z, Zhou J, Li X, Liu Z, Li Y, Chen H. Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction. EMBO Rep. 2020 Aug 5;21(8):e49583. doi: 10.15252/embr.201949583. PubMed Source
  • 15
    Lemon JA, Boreham DR, Rollo CD. A complex dietary supplement extends longevity of mice. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):275-9.  PubMed Source
  • 16
    Brown MK, Evans JL, Luo Y. Beneficial effects of natural antioxidants EGCG and alpha-lipoic acid on life span and age-dependent behavioral declines in Caenorhabditis elegans. Pharmacol Biochem Behav. 2006 Nov;85(3):620-8. PubMed Source 
  • 17
    Farr SA, Price TO, Banks WA, Ercal N, Morley JE. Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. J Alzheimers Dis. 2012;32(2):447-55. PubMed Source
  • 18
    Gleiter CH, Schug BS, Hermann R, Elze M, Blume HH, Gundert-Remy U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol. 1996;50(6):513-4. PubMed Source
  • 19
    DAVID SINCLAIR “Alpha Lipoic Acid For Mitochondrial Health” | Dr David Sinclair Interview Clips. URL
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