Effects of alpha-lipoic acid on the plasma levels of asymmetric dimethylarginine in diabetic end-stage renal disease patients on hemodialysis: a pilot study.
OBJECTIVE
Endothelial dysfunction due to reduced nitric oxide (NO) availability precedes the development of atherosclerosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is not only a cause of endothelial dysfunction, but also a predictor of the cardiovascular outcome in end-stage renal disease (ESRD) patients on hemodialysis (HD). Alpha-lipoic acid (ALA), a strong antioxidant, increases NO-mediated vasodilation in diabetic patients. We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD.


METHODS
Fifty patients undergoing HD three times per week were randomized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group. We measured the plasma levels of cholesterol, albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA in both groups at baseline and at 12 weeks.


RESULTS
In the control group, the levels of total cholesterol, serum albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA did not change. In the treatment group, the plasma levels of ADMA decreased significantly from a median of 1.68 (range 0.45-3.78) microM to a median of 1.31 (range 0.25-3.19) microM (p = 0.001).


CONCLUSIONS
Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients, ALA may have the potential of a beneficial effect in them, in part by decreasing the plasma level of ADMA.
Chang
Jai Won
JW
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Lee
Eun Kyoung
EK
Kim
Tae Hee
TH
Min
Won Ki
WK
Chun
Sail
S
Lee
Ki-Up
KU
Kim
Soon Bae
SB
Park
Jung Sik
JS
D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications* / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology / Q000628:therapy; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction / Q000187:drug effects; D010865:Pilot Projects; D006435:Renal Dialysis; D008063:Thioctic Acid / Q000627:therapeutic use*; D016896:Treatment Outcome
D000975:Antioxidants; D001120:Arginine; D015415:Biomarkers; D002097:C-Reactive Protein; D002784:Cholesterol; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; D019001:Nitric Oxide Synthase; D008063:Thioctic Acid; C099252:oxidized low density lipoprotein; C018524:N,N-dimethylarginine