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Alpha Lipoic Acid and Healthy Nervous System Function:
An interview with Dr. Vijayshree Yadav, M.D.
Q: Dr. Yadav, you have recently completed some very interesting research regarding alpha lipoic acid, which was published in the April 11th issue of Mult Scler. 2005. Can you give us a little background about yourself as well as your research interests involving alpha lipoic acid?
A: My name is Vijayshree Yadav, MD. I am a board certified neurologist and I completed my fellowship in neuroimmunology at Oregon Health & Science University/Portland VA Medical Center. My most recent project was a pilot study conducted with my mentor, Dr. Dennis Bourdette. This was a 14-day trial involving 37 subjects divided into four groups, including placebo. The doses of alpha lipoic acid within the supplemented groups were 600 mg twice per day, 1200 mg once per day and 1200 mg twice per day. The idea was to assess the tolerability and peak serum levels of alpha lipoic acid as well as its affect on matrix metalloproteinase-9 (MMP-9) activity and nervous system endothelial cell function.
Q: Why did you feel that alpha lipoic acid was an ideal choice for this study?
A: Alpha lipoic acid is a natural antioxidant with a history of use for nerve support. The main rationales for using alpha lipoic acid involves it’s potential capability to maintain healthy MMP-9 activity and endothelial cell membrane integrity. Proteins such as MMP-9 and certain endothelial cell proteins have an important role in movement of T cells into the central nervous system. We believe alpha lipoic acid can moderate the function of these proteins and thus can help preserve the structural integrity of nervous system cells. In a recent cell study, we demonstrated that alpha lipoic acid maintains healthy MMP-9 mRNA production. We found it to be supportive of immunological and neurological function in an animal model as well, so it made great sense for us to pursue this role of alpha lipoic acid in a pilot study.
Q: What are optimal serum levels of alpha lipoic acid? Why do you think serum levels varied considerably for individuals supplementing with the same dosage?
A: We do not know what the optimal serum levels would be. Median levels for subjects taking a dose of 1200 mg alpha lipoic acid were substantially higher (4.8 mg/ml) than for subjects taking 600 mg (0.2 mg/ml). However, there was considerable inter-subject variability. Subjects taking 600 mg had peak serum levels ranging from 0 to 3.7 mg/ml. Subjects taking 1200 mg had peak serum levels ranging from 0 to 19 mg/ml. Serum levels varied because the absorption of alpha lipoic acid varies in different individuals and also because food affects the absorption of lipoic acid.
Q: How did alpha lipoic acid serum levels correlate with MMP-9 activity?
A: A statistically significant correlation was found between peak serum alpha lipoic acid levels and healthy MMP-9 activity. We did not find a statistically significant difference in MMP-9 activity between the groups, however this may be due to the small study sample size.
Q: How did alpha lipoic acid serum levels correlate with nervous system endothelial cell function?
A: In this case, peak levels didn’t matter as much as did total alpha lipoic acid intake, in which case 1200 mg twice per day tended to be more supportive than 1200 mg once per day. Interestingly, our results suggest that MMP-9 activity may be influenced by peak serum levels whereas sustained blood levels of alpha lipoic acid may have more of an influence on the health of other markers of endothelial function.
Q: You found no change in complete blood count, metabolic panel or urine analysis results from alpha lipoic acid supplementation. Was alpha lipoic acid at the study levels well-tolerated and were any side effects reported?
A: Three subjects experienced nausea, one subject developed fever, mild thrombocytopenia and an allergic rash that was resolved without treatment upon discontinuing alpha lipoic acid. The most common side effects were malodorous urine and gastrointestinal side effects such as mild nausea and discomfort.
Q: What are your future study plans?
A: My goal is to conduct a phase I/phase II clinical trial on the neuro and immuno modulating properties of alpha lipoic acid. I would like to examine the immunological effects of 6 months administration of alpha lipoic acid in a group of individuals. This would be conducted at the General Clinical Research Center at Oregon Health Science University. The primary goal of the study would be to assess the role of alpha lipoic acid in maintaining healthy MMP-9 and endothelial cell function along with other parameters. The secondary outcomes would include assessment of safety of high dose alpha lipoic acid administration and benefits from 6 months of alpha lipoic acid use. The study would also further explore pharmacokinetics. The plan is to include sixty subjects randomized to receive either placebo or 1200 mg alpha lipoic acid twice a day. This proposal has been supported by the NIH.
The information contained herein is for informational purposes only and does not establish a doctor-patient relationship. Please be sure to consult your physician before taking this or any other product. Consult your physician for any health problems.
*These statements have not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.
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