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12-18-2011, 06:45 PM | #1 | |||
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http://www.medscape.com/viewarticle/725699
...To discern the etiology of PN in IPD patients, the authors examined a number of known causes of neuropathy, most of which were unrevealing. Although similar cobalamin levels were found in the IPD groups with and without PN, fasting homocysteine and methylmalonic acid (MMA) levels were significantly higher in the IPD group with PN. The odds ratio for exposure to L-dopa in the IPD patients with PN was 12.4 (95% confidence interval, 1.4–109.1). ...Cumulative L-dopa exposure was associated not only with PN, but also with elevated fasting MMA levels across all IPD patients in the study. L-dopa exposure was also associated with PN severity in the IPD patients with PN. This intriguing study demonstrates a somewhat unexpectedly high prevalence of PN in IPD patients and cites an association with elevated MMA levels, perhaps mediated by exposure to L-dopa. L-dopa may indeed interact with methylation pathways involved in folate metabolism, providing a mechanism for MMA elevation....if verified, this study may change the way we care for patients with IPD. PN in IPD could substantially contribute to gait disturbance and disability in some patients with IPD, and prevention of PN would be an important advance. Exposure to L-dopa is inevitable in most IPD patients at some point during their course, but perhaps we should be measuring MMA levels in these patients and treating with cobalamin supplementation to reduce MMA levels and prevent neuropathy. Further studies, including treatment trials, seem warranted. (FYI: Methylmalonic acid is a precursor to the production of succinyl-CoA which is a key part of the Kreb’s cycle. Anyone who has studied biochemistry cringes when they hear the words “Kreb’s Cycle” because memorization and understanding of this process is the key to understanding human metabolism and energy production. The step of enzymatic conversion of the Methylmalonic –CoA into succinyl-CoA requires vitamin B12, and as a result methylmalonic acid levels are reliably elevated in patients with vitamin B12 deficiency.http://methylmalonicacid.org/)
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