Eur J Clin Invest. 2010 (Feb); 40 (2): 148–154
Heinisch BB, Francesconi M, Mittermayer F, Schaller G, Gouya G, Wolzt M, Pleiner J.
Medical University of Vienna, Vienna, Austria.
Diabetes mellitus is a chronic condition where the body does not produce or does not use insulin effectively. Type 2 diabetes appears to be caused by genetic defects that at first make a person not able to respond to the actions of insulin and, over time, the beta cells in the pancreas will stop releasing insulin. The long-term complications associated with diabetes are serious, often life-threatening, and diagnosed in the late stages of the disease. These changes include coronary heart disease and peripheral vascular disease, retinopathy, nephropathy, and neuropathy.
Vascular endothelial dysfunction promotes vasoconstriction and favors platelet aggregation, white blood cell adhesion, and smooth muscle cell proliferation. It is the hallmark for vascular diseases and is often regarded as the primary event in the development of atherosclerosis. Endothelial dysfunction is often seen in patients with coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia.
Alpha-lipoic acid (ALA) is referred to as alpha-lipoate, thioctic acid, or just lipoic acid. It is one of the most powerful antioxidants ever discovered. In the body, alpha-lipoic acid is converted to dihydrolipoic acid (DHLA), which also functions as a strong antioxidant. Lipoic acid is part of two enzyme systems: PDH (pyruvate dehydrogenase) and alpha-ketoglutarate dehydrogenase. These enzymes are part of the Krebs cycle and are essential in the production of energy.
This randomized, controlled, double-blinded study was performed at the Medical University of Vienna in Vienna, Austria and the purpose was to investigate whether ALA could be effective in treating endothelial dysfunction. The researchers recruited 30 patients with type 2 diabetes and proceeded to measure forearm blood flow (FBF) before and after 21 days of either intravenous treatment with 600 mg alpha-lipoic acid or placebo. In the beginning of the trial FBF responses were comparable in all patients. The patients treated with placebo experienced no change in FBF while the patients treated with ALA experienced improved vascular endothelial function. In conclusion, alpha-lipoic acid may reduce the risk of vascular endothelial dysfunction.
OBJECTIVE: The aim of this study was to investigate the effect of alpha-lipoic acid (ALA) treatment on endothelium-dependent and -independent vasodilatation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus.
RESEARCH DESIGN AND METHODS: A total of 30 subjects with type 2 diabetes were included in this randomized, controlled, double-blinded, parallel group study. FBF responses to intra-arterial acetylcholine (ACh) and glycerol trinitrate (GTN) were measured before and after 21 days of intravenous treatment with 600 mg alpha-lipoic acid or placebo.
RESULTS: FBF responses were comparable at baseline. After treatment, FBF reactivity to ACh and GTN was unchanged in subjects receiving placebo. By contrast, ALA treatment increased endothelium-dependent vasodilatation to ACh (P < 0.05) but not to GTN compared with baseline.
CONCLUSIONS: Intravenous ALA treatment improves endothelium-dependent vasodilatation in patients with type 2 diabetes, in the absence of effects on forearm vasomotor function. If this salutary action translates into vascular risk reduction remains to be established.