R-Lipoic Acid vs Alpha-Lipoic Acid: Which Is The Best Antioxidant? (2024)

Energy

By Performance Lab
Last Updated: Oct 12, 23
7 minute read

Antioxidants are a big thing in the wellness world, and there’s no question as to why. Whether it’s environmental toxins, food chemicals, or intense exercise, free radicals seem to come from all angles.

And while the body is equipped with what it needs to neutralize and eliminate radicals to prevent damage, sometimes endogenous stores run low, or our antioxidant system isn't running as it should be.As a result, free radicals exceed what our antioxidant defense system can deal with, and we’re left with oxidative stress.

Because oxidative stress underlies a number of diseases, loading up on antioxidants is never a bad thing. We want you to give your body a little extra love. With that said, we’re talking about one of the antioxidants that doesn’t get much attention—lipoic acid.

But if you’re looking for a lipoic acid supplement, there are a couple of forms you’ll find. We’ve done the work for you, and we’re breaking down the benefits of lipoic acid and the more effective form for antioxidant protection.

What Is Lipoic Acid?

Lipoic acid, usually referred to as alpha-lipoic acid or ALA, is an organosulfur compound derived from caprylic acid. In humans, alpha-lipoic acid is naturally produced in the mitochondria, but is also found in several food sources.

Endogenously synthesized alpha-lipoic acid is protein-bound and serves as a cofactor for several critical mitochondrial multienzyme complexes involved in energy production and amino acid metabolism ¹.

There are two main forms of lipoic acid that you’ll see: R- and S-enantiomers ¹. These enantiomers are mirror images of each other, but only the R-form is synthesized by the body and bound to proteins but also found in food sources. In supplements, you’ll generally find only R-lipoic acid or a 50/50 mix of S-lipoic acid and R-lipoic acid.

However, the therapeutic effect of supplemental lipoic acid is often attributed to its role as an antioxidant. Both DHLA, the reduced form of lipoic acid, and lipoic acid itself possess metal-chelating capacity and scavenge ROS, but DHLA can also regenerate endogenous antioxidants (vitamin E, vitamin C, and glutathione) and repair oxidative damage ².

But the one super beneficial thing about lipoic acid as an antioxidant is that it’s both water-soluble and fat-soluble—whereas most other antioxidants are either or—which makes it a powerful radical scavenging agent in virtually every cell and tissue in the body ³.

The Benefits Of Lipoic Acid

1. Antioxidant

The antioxidant function of lipoic acid is perhaps its most well-known role in the human body, and it’s the major reason we’re huge fans of it.

As we said, as both a water- and fat-soluble antioxidant, it steps ahead of most other endogenous and exogenous antioxidants that are only water-soluble like vitamin C or only fat-soluble like vitamin E. As a powerful antioxidant, there are a few functions in which lipoic acid is involved in:

Scavenging RONS: Reactive oxygen and nitrogen species are highly reactive compounds that can damage DNA, proteins, and lipids in cell membranes. Both lipoic acid and DHLA act as direct radical scavengers that neutralize radical molecules and protect cells from damage ⁴.
Antioxidant regeneration: When antioxidants scavenge free radical molecules, in the process of neutralization they become oxidized and cannot scavenge additional radicals until they have been reduced. Lipoic acid, however, is a powerful reducing agent that can reduce several key antioxidants, including CoQ10, vitamin C, vitamin E, and glutathione ^5-7.
Metal chelation: Heavy metal toxicity is something that’s come to the forefront for a lot of wellness gurus because it can have major impacts on neurological function. Metals like iron and copper can induce oxidative damage by acting as catalysts for reactions that generate free radicals. Both lipoic acid and DHLA have been shown to prevent copper and iron-mediated oxidative damage, which may be beneficial for neurodegenerative conditions and other diseases where oxidative stress is an underlying component ^{8, 9}.
Activates signaling pathways: Glutathione (GSH) is one of the most powerful endogenous antioxidants in the human body that also plays a role in the detoxification and elimination of carcinogens and toxins. Decreases in GSH synthesis and tissue concentrations can reduce the body’s ability to deal with oxidative stress, but research shows that lipoic acid may enhance the synthesis of GSH via upregulating expression of γ-glutamylcysteine ligase (γ-GCL), the rate-limiting enzyme involved in its production, but also by increasing cellular uptake of cysteine, a precursor amino acid required for GSH synthesis ^{10, 11}.

2. Regulates Glucose Uptake

Diet plays a major role in mitigating the risk of diabetes and controlling blood sugar, but if you’re looking for supplements that help, recent research suggests ALA might help to increase insulin sensitivity and reduce blood sugar and lipids.

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As a compound that plays an essential role in mitochondrial bioenergetic reactions, it’s gained a fair bit of attention as an antioxidant for use in managing diabetic complications ¹².

Research shows that one important action of lipoic acid for blood glucose is the expression of AMPK in the hypothalamus and peripheral tissues. AMPK activation inhibits certain energy-consuming biosynthetic pathways and the activation of ATP-producing catabolic pathways ¹².

Additionally, AMPK also influences the transcription of specific genes involved in energy metabolism, thus exerting long-term metabolic control.

A 2011 study looked at the effects of alpha-lipoic acid supplementation over two months on fasting blood glucose (FBG), insulin resistance (IR), and glutathione peroxidase (GH-Px) activity in type 2 diabetics ¹³.

Results showed that 300mg daily of ALA was beneficial for reducing FBG and post-prandial plasma glucose (PPG) levels, along with insulin resistance and GH-Px activity, suggesting that it may be a beneficial supplement for people dealing with metabolic dysregulation.

3. Reduces Inflammation

Chronic inflammation is a major factor that underlies many chronic diseases, including diabetes, CVD, arthritis, and even cancer ¹⁴. Research suggests that ALA supplementation can help to reduce certain markers of inflammation such as C-reactive protein (CRP), NF-kB, ICAM-1, VCAM-1, MMP-2, MMP-9, IL-6, and TNF-α ^15-20.

Its role in mitigating inflammation may also be the link for its efficacy with blood glucose control and diseases involving metabolic dysfunction.

4. Weight Loss

Along with regulating glucose uptake, ALA’s ability to reduce AMPK activity may benefit weight loss; AMPK functions as a fuel sensor in cells and is activated when cellular energy is depleted ²¹.

ALA is a cofactor of mitochondrial enzymes that can suppress the activity of AMPK, which may result in weight loss by reducing food intake and appetite, and enhancing energy expenditure. However, the extent to which ALA can support weight loss is still debatable.

What’s The Difference Between R-Lipoic Acid And Alpha-Lipoic Acid?

As mentioned before, most lipoic acid supplements are a 50/50 mix of R-lipoic acid and S-lipoic acid, both of which are enantiomers of alpha-lipoic acid.

R-lipoic acid as a sole supplement has significant benefits for everything we’ve talked about, but studies suggest that supplements containing pure R-lipoic acid are better absorbed than supplements containing a mix of R- and S-lipoic acid.

While both forms of lipoic acid offer health benefits, we gravitate towards bioenhanced R-lipoic acid like what’s found in Performance Lab® Energy.

Bio-Enhanced® Na-RALA is a purified, stabilized, and nature-identical salt form that helps eliminate gastric side effects associated with lipoic acid supplementation and maximize bioavailability.

In Energy, you’re getting ALCAR + ALA synergy to support mitochondrial synthesis and energy metabolism more effectively than when either supplement is taken alone.

Get the best price on Performance Lab Energy here

Final Thoughts

In a world that constantly throws free radicals our way, getting enough antioxidants—both through diet and supplementation—is key for maintaining optimal function throughout a lifestyle.

If you’ve already got vitamin C, vitamin E, and GSH in your supplement stack, it only makes sense that you add in the helping hand, lipoic acid.

It’s scientifically proven to be effective for supporting endogenous antioxidant defenses, and it’s one of our favorite picks for supporting energy production, mitigating free radicals and subsequent cell damage, and promoting health across all body systems.

References

L Packer, E Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling.J Clin Biochem Nutr. 2011;48(1):26-32.
GP Biewenga, GR Haenen, A Bast. The pharmacology of the antioxidant lipoic acid.Gen Pharmacol. 1997;29(3):315-331.
S Golbidi, M Badran, I Laher. Diabetes and alpha lipoic Acid.Front Pharmacol. 2011;2:69.
AR Smith, SV Shenvi, M Widlansky, JH Suh, TM Hagen. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 2004;11(9):1135-1146.
W Jones, X Li, ZC Qu, L Perriott, RR Whitesell, JM May. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Free Radic Biol Med. 2002;33(1):83-93.
Kozlov AV, Gille L, Staniek K, Nohl H. Dihydrolipoic acid maintains ubiquinone in the antioxidant active form by two-electron reduction of ubiquinone and one-electron reduction of ubisemiquinone. Arch Biochem Biophys. 1999;363(1):148-154.
May JM, Qu ZC, Mendiratta S. Protection and recycling of alpha-tocopherol in human erythrocytes by intracellular ascorbic acid. Arch Biochem Biophys. 1998;349(2):281-289.
P Ou, HJ Tritschler, SP Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol. 1995;50(1):123-126.
JH Suh, BZ Zhu, E deSzoeke, B Frei, TM Hagen. Dihydrolipoic acid lowers the redox activity of transition metal ions but does not remove them from the active site of enzymes. Redox Rep. 2004;9(1):57-61.
JH Suh, SV Shenvi, BM Dixon, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004;101(10):3381-3386.
JH Suh, H Wang, RM Liu, J Liu, TM Hagen. (R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Arch Biochem Biophys. 2004;423(1):126-135.
S Golbidi, M Badran, I Laher. Diabetes and alpha lipoic Acid.Front Pharmacol. 2011;2:69.
H Ansar, Z Mazloom, F Kazemi, M Hejazi. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients.Saudi Med J. 2011;32(6):584-588.
R Pahwa, A Goyal, P Bansal, et al. Chronic Inflammation. (Updated 2021 Sep 28). In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2021 Jan-.Available from: https://www.ncbi.nlm.nih.gov/books/NBK493173/
S Saboori, E Falahi, E Eslampour, M Zeinali Khosroshahi, E Yousefi Rad. Effects of alpha-lipoic acid supplementation on C-reactive protein level: A systematic review and meta-analysis of randomized controlled clinical trials. 2018;28(8): 779-786.
S Sola, MQ Mir, FA Cheema, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. 2005;111(3):343-348.
P Chaudhary, GH Marracci, DN Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis.J Neuroimmunol. 2006;175(1-2):87-96.
Z Cavdar, S Ozbal, A Celik, et al. The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model.Biotech Histochem. 2014;89(4):304-314.
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