Reference
Bobe G, Michels AJ, Zhang WJ, et al. 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. J Nutr. 2020;150(9):2336-2345.
Study Objective
Primary: Assess the efficacy of (R)-alpha lipoic acid (R-LA) in reducing elevated plasma triglycerides in overweight and obese adults
Secondary: Assess efficacy of alpha-lipoic acid in promoting weight loss and/or improving oxidative stress and/or inflammation
Design
Randomized, double-blind, placebo-controlled trial
Intervention
The duration of the trial was 24 weeks. Participants received either 2 capsules containing 300 mg R-LA each or matched inert tablets on an empty stomach 30 minutes before breakfast. Researchers asked the participants not to change any other aspect of diet or lifestyle during the course of the study.
Participants
The trial involved 81 adults (57% women; aged 21 to 60 years; body mass index [BMI] ≥ 25 kg/m2).
All participants had elevated baseline plasma triglycerides (≥100 mg/dL).
Study Parameters Assessed
Primary:
- Plasma triglycerides
Secondary:
- Bodyweight and body fat mass
- Cellular and plasma antioxidant pool and capacity
- Gene expression of antioxidant enzymes
- Lipid peroxidation
- Cellular and plasma markers of inflammation
- Blood markers of immune surveillance
Primary Outcome Measures
Change in plasma triglycerides.
Key Findings
- Plasma triglycerides did not decrease with R-LA supplementation.
- Treatment group had a greater reduction in BMI at 24 weeks than the placebo group (−0.8; P=0.04)
- At 24 weeks, women and obese participants in the treatment group (BMI ≥35) lost the most weight (−5.0% and −4.8%, respectively; both P<0.001) and body fat (−9.4% and −8.6%, respectively; both P<0.005).
- Antioxidant gene expression in mononuclear cells, as expressed by heme oxygenase 1 (HMOX1) genetic expression, was higher in the treatment group at 24 weeks.
- Multiple markers assessing oxidative stress and inflammation were lower in the treatment group at 24 weeks, including less urinary F2-isoprostanes (−25%; P=0.005).
Practice Implications
In some people, obesity and overweight are strongly correlated to concomitant health risks including elevated triglycerides,1,2 inflammation,3 and oxidative stress.4
The extent to which these physiological changes can impact overall health5 and mortality6 is significant and warrants a multidisciplinary approach in working with this patient population.
At 24 weeks, women and obese participants in the treatment group (BMI ≥35) lost the most weight.
The journey of thoroughly and permanently implementing foundational, health-promoting lifestyle changes can be a long, winding, arduous one. Therefore, taking advantage of supplementary aids to help people improve their BMI makes sense. When that support works directly to improve key physiological factors that may otherwise contribute to eventual pathological changes, it makes even more sense.
Although this study showed no effect in terms of its primary outcome, impacts seen in various secondary outcomes strongly suggest that R-LA may still fit that bill. Arguably, the changes in the intervention group may have a more impactful contribution to health than the primary outcome measure does.
While this study did not show that R-LA lowered triglycerides, the clear impacts on inflammation and oxidative stress that this nutrient appears to have in this patient population make R-LA clinically relevant. This is especially the case when one considers the negative impacts of inflammation and oxidative stress on cardiovascular risk induced by hypertriglyceridemia.6,7
Theoretically, the lack of effect seen in R-LA’s primary outcome measure of plasma triglycerides could be interpreted to mean there is no utility in R-LA use. However, triglycerides are not thought to be directly atherogenic themselves, but rather a biomarker of risk because they frequently correlate with other atherogenic factors.8
In fact, an elevation in triglycerides may have questionable negative impacts when inflammation is under control. Some evidence suggests that clear effects on endpoint markers of cardiovascular disease may occur even when triglycerides increase with treatment if inflammation and oxidative stress improve.9
As always, we should strive for using a multipronged approach in the care of patients, well-grounded in foundational health-promoting principles (diet, exercise, sleep, stress reduction, etc.). However, various real-life circumstances that can come into play during patients’ efforts may slow or hinder their progress. Having additional tools like R-LA on board, or at the ready, can serve to protect our patients in important ways while they work toward ever-improving health-promoting lifestyle practices and an improved level of health.
