A compound given as a dietary supplement to overweight but otherwise healthy people in a clinical trial caused many of the patients to lose weight, according to research by Oregon State University and Oregon Health & Science University. The research, ‘A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations’, was published in The Journal of Nutrition.
"The data clearly showed a loss in body weight and body fat in people taking lipoic acid supplements," said Dr Balz Frei, director emeritus of OSU's Linus Pauling Institute and one of the scientists on the study. "Particularly in women and in the heaviest participants."
Produced by both plants and animals, lipoic acid sets up shop in cells' mitochondria, where it's normally attached to proteins involved in energy and amino acid metabolism. A specialised, medium-chain fatty acid, it's unique in having two sulphur atoms at one end of the chain, allowing for the transfer of electrons from other sources.
The body generally produces enough lipoic acid to supply the enzymes whose proper function requires it. When taken as a dietary supplement, lipoic acid displays additional properties that might be unrelated to the function in the mitochondria. They include the stimulation of glucose metabolism, antioxidant defences and anti-inflammatory responses, making it a possible complementary treatment for people with diabetes, heart disease and age-related cognitive decline.
"Scientists have been researching the potential health benefits of lipoic acid supplements for decades, including how it might enhance healthy aging and mitigate cardiovascular disease," said Dr Alexander Michels, another Linus Pauling Institute scientist involved with the study. "In both rodent models and small-scale human clinical trials, researchers at the LPI have demonstrated the beneficial effects of lipoic acid on oxidative stress, lipid metabolism and circadian rhythm."
The primary objective of the trial was to evaluate whether lipoic acid supplementation decreases elevated plasma triglycerides in overweight or adults with obesity. Secondary aims examined if lipoic acid promotes weight loss and improves oxidative stress and inflammation.
The study recruited 81 overweight adults (57% women) with elevated plasma triglycerides ≥100mg/dL were enrolled in a 24 week, randomised, double-blind, controlled trial, assigned to either (R)-α-lipoic acid (R-LA; 600 mg/d) or matching placebo, and advised not to change their diet or physical activity. Linear models were used to evaluate treatment effects from baseline for primary and secondary endpoints.
The outcomes showed that R-LA did not decrease triglyceride concentrations, but individuals on R-LA had a greater reduction in BMI at 24 weeks vs. placebo group (p=0.04). The effect of R-LA on BMI was correlated to changes in plasma triglycerides (p=0.004). Improvement in body weight was greater at 24 week in R-LA subgroups than in placebo subgroups. Women and participants with BMI ≥35 showed greater weight loss (−5.0% and −4.8%, respectively; both p<0.001) and loss of body fat (−9.4% and −8.6%, respectively; both p<0.005). Antioxidant gene expression in mononuclear cells at 24 week was greater in the R-LA group (Heme oxygenase 1 [HMOX1] : +22%; p=0.02) than in placebo. Less urinary F2-isoprostanes (−25%; P = 0.005), blood leukocytes (−10.1%; p=0.01), blood thrombocytes (−5.1%; p=0.03), and ICAM-1 (−7.4%; p=0.04) at 24 week were also observed in the R-LA group than in placebo.
"Many existing clinical studies using lipoic acid have focused on volunteers with pre-existing conditions like diabetes, making it difficult to determine if lipoic acid supplements simply act as a disease treatment or have other beneficial health effects," said Dr Tory Hagen, a professor of biochemistry and biophysics in the OSU College of Science and the study's corresponding author. "Another issue is the formulation of the supplement. Many previous studies have used the S form of lipoic acid, which is a product of industrial synthesis and not found in nature. We only used the R form of lipoic acid—the form found in the body naturally."
Identifying which patients will benefit the most from lipoic acid supplementation, and how much they need, is important for both clinical and economic reasons, he added.
"By the end of the study, some markers of inflammation declined. The findings also suggest that lipoic acid supplementation provides a mild reduction in oxidative stress. It is not a perfect panacea, but our results show that lipoic acid supplements can be beneficial. Lipoic acid supplements are often quite expensive. So understanding how we can maximise benefits with smaller amounts of the supplement is something we are interested in pursuing."