Jonathan V. Wright M.D.

For nearly three decades, Dr. Tory Hagen has worked to understand how lipoic acid supplements act in the body. His journey began under the mentorship of Dr. Bruce Ames at the University of California, Berkeley. Together, Hagen and Ames started on the path to understand how and why we age with the hope of learning how to live longer and feel better.

Lipoic Acid Supplements and Weight Loss
A New Clinical Trial Sheds Light on the Benefits
By Dr. Tory M. Hagen, Ph.D.

Investigators at the Linus Pauling Institute, along with their collaborators at Oregon Health & Science University, recently published results of a clinical trial using lipoic acid supplements. This study shows that lipoic acid supplements can help some people lose weight.

For over 20 years, scientists and clinicians have explored the potential health benefits of lipoic acid, including its ability to promote healthy aging and mitigate cardiovascular disease.

Researchers at the Linus Pauling Institute have documented that lipoic acid reduces oxidative stress and improves detoxification mechanisms and lipid metabolism. Although this work is primarily in rodent models, human trials at the Institute found that lipoic acid replicates some of the same effects listed above and may play a role in maintaining a normal circadian rhythm.

What is Lipoic Acid?

Lipoic acid is a naturally occurring compound produced by both plants and animals. It has a structure that is unique in nature: chemically, it is a medium-chain fatty acid with two sulfur atoms at one end.

Lipoic acid is typically found attached to enzymes, where it acts as an electron carrier. Therefore, it should be no surprise that these enzymes are involved in energy and amino acid metabolism in the mitochondria.

The body usually produces adequate amounts of lipoic acid to meet its metabolic needs.

However, something different happens when lipoic acid is taken as a supplement. Often marketed as alpha-lipoic acid, the molecule is found in a free (not protein-bound) form. This allows it to take other actions in the body, like stimulating certain types of cell signaling.

Lipoic acid supplements have been shown to stimulate glucose metabolism, antioxidant defenses, and anti-inflammatory responses. For these reasons, lipoic acid has been investigated as a complementary treatment for people with diabetes, heart disease, and age-related cognitive decline.

Changing Focus

These studies laid the foundation for better human trials. Dr. Tory Hagen, the Linus Pauling Institute’s expert on lipoic acid, just released the results of a clinical trial on lipoic acid in The Journal of Nutrition, renewing interest in the beneficial effects of lipoic acid supplements.

Over the last few decades, there have been a number of clinical studies on lipoic acid. However, Dr. Hagen and other researchers in this field felt the study designs of the previous trials needed improvement.

One persistent issue was the choice of study participants. In short, the previous trials focused on volunteers with pre-existing conditions like diabetes. This made it difficult to tell if the benefits were due to lipoic acid supplements improving disease or if lipoic acid supplements would provide potential benefits for people without a chronic disease.

Another issue was the formulation of the supplement. “Commercially, lipoic acid is often found in a combination of the R– and S- forms of the molecule, ” explained Dr. Hagen. “However, the R-form of lipoic acid is the only form that is naturally found in the body.”

Dr. Hagen has long been an advocate of only using the R-form of lipoic acid in his experiments and clinical studies because it is the form that has all the biological activity. There are some indications that the R-form is better absorbed, has fewer gastrointestinal side effects, and may act on target tissues better than the S-form of the molecule.

New Study, New Revelations

The latest study published by the Linus Pauling Institute last year was a joint effort with Oregon Health & Science University. Participants took either 600 mg per day of R-lipoic acid or a placebo for 24 weeks (roughly six months).

The study focused on people who were both overweight and had high triglyceride levels. The primary objective was to see if lipoic acid supplementation could reduce the amount of triglycerides in the blood. The principal investigators were careful not to include people who had a diagnosed disease.

In the end, some of the results were surprising. The analysis showed that the group taking lipoic acid did see a reduction in their blood triglyceride levels overall. Instead, it was clear that many participants taking lipoic acid were losing weight.

“The data clearly showed a loss of body fat that resulted in weight loss,” says Dr. Gerd Bobe, study statistician and coauthor on the study. “In some people, this resulted in lower triglyceride levels, but the weight loss had to come first.”

Some groups showed greater weight loss than others. For example, in female study participants there was over a 10% reduction in body fat in the lipoic acid group when compared to the placebo group.

Lipoic acid supplements had other effects as well. For example, participants in the lipoic acid supplement group had lower urinary F2 isoprostane levels than the placebo. This biomarker suggests that these participants were experiencing less oxidative stress.

However, it was unclear if these biomarker changes were due to the weight loss or if lipoic acid affected these biomarkers independently. Future trials by the Institute will likely focus on differentiating these effects.

The Future of Lipoic Acid Supplements

“This study shows that lipoic acid supplements can be beneficial,” said Hagen. “But like many dietary supplements, it’s possible that the effects won’t be seen by everyone taking them. Right now, it is not a perfect panacea.”

Dr. Hagen points out that just over one-third of the study participants in the lipoic acid group did not lose weight during the trial. While this was clearly an improvement over taking a placebo (in the placebo group about half of the participants gained weight), it suggests that lipoic acid might have limited effect on its own.

Also, some of the participants in this study reported side effects of the supplements like heartburn or stomach aches. Side effects are not uncommon with lipoic acid supplements, especially when taking large doses on an empty stomach.

Furthermore, cost can be an issue. Lipoic acid supplements, especially R-lipoic acid, are often quite expensive. So, it can be a costly endeavor to find out that they might not work out for you.

“If lipoic acid works better in some people and not others, we need to know why,” concludes Hagen. “It will make for a more targeted approach to lipoic acid supplementation in the future.”


Bobe et al. J Nutr 150 (2020) doi: 10.1093/jn/nxaa203
Keith et al. Biochem Biophys Res Commun 450 (2014) doi: 10.1016/j.bbrc.2014.05.112
Keith et al. Pharmacol Res 66 (2012) doi: 10.1016/j.phrs.2012.05.002

About Dr. Tory Hagen, Ph.D.

After coming to the Linus Pauling Institute in 1998, Dr. Hagen’s research team consistently published on the effects of lipoic acid supplementation in older animals. From maintaining cellular antioxidant levels to cell-signaling pathways, each study found similar results: lipoic acid could make old animals appear like young animals, at least biochemically.

In recent years, Dr. Hagen’s focus has transitioned into human studies. Although there are some clinical data demonstrating the utility of lipoic acid in diabetes treatment, there is still little evidence for lipoic acid supplements in otherwise healthy older adults. As more research emerges, Dr. Hagen hopes that funding for these trials in older adults will follow. Ultimately, it will help everyone discover if supplements like lipoic acid may be beneficial in our pursuit of health.

Reprinted from the Linus Pauling Institute Oregon State University Research Newsletter – Winter 2021 by permission.

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