http://www.medscape.com/viewarticle/752984
"Our results support the possibility that genetically predisposed patients with Parkinson's disease may develop levodopa-induced vitamin B12 deficiency with subsequent neurotoxic methylmalonic acid accumulation," the authors report.

"In view of these data," the editorialists add, "we now need well-designed unselected population-based investigations and at best prospective epidemiologic studies, as well as experimental and clinical/electrophysiologic studies either demonstrating or refuting a direct causative link between levodopa exposure in idiopathic Parkinson's disease, neuropathy, and vitamin B12 deficiency or increased homocysteine and methylmalonic acid."

Meanwhile, what should be done for patients with Parkinson's disease?

The investigators call for clinical assessment of neuropathy in patients treated with levodopa on a long-term basis. They also recommend a classic workup including vitamin B12, homocysteine, methylmalonic acid levels in patients with confirmed neuropathy.

Finally, they suggest possible systematic B12 or folate supplementation.

Imad

That's me. Got diagnosed with pernicious anaemia (B12 def.) earlier this year.

I'll have to research what 'neurotoxic methylmalonic acid accumulation' means.

I certainly have developed the most painful legs along with it and no-one seems to know what to do about them other than give me some truly hideous stockings. I am getting the B12 and folate supplementation, but can't say that it has improved the way I feel.

The deficiency itself can cause nerve damage, and demyelination with spinal cord involvement (subacute combined degeneration of the spinal cord). A good reason to get it checked out.......

Interestingly there is also a Helicobactor pyelori connection. Does l-dopa accelerate this, cause it, or is it a predisposition? There is little out there to help people find out.... Rick, would be interested to know how you would fit this into the braak stuff, is it another chicken and egg thing?

My doctor says that most cases are discovered when looking at regular blood workups, quite by accident, and often get missed as different countries use different levels to assess the normal reading. There is not a real consensus on what is a deficiency, until it is really abnormally low. The pernicious anaemia society (PAS) has a lot of people who say the supplementation by injection has it's own problems, and often does not last long enough. Another group of struggling people who are trying to find answers.......

Thanks for posting this......

I believe that long-term Vitamin B12 deficiency was a significant factor in my mom's development of PD. Her 23andme genetic results show that she is +/+ for a mutation on the MTRR gene (rs1801394), which means she has a reduced ability to generate the methyl form of B12 (active form most directly involved with neurological health). The other gene she is +/+ for a mutation is MTHFR (rs1801131), which involves recycling of BH2 back to BH4, so she likely has lower BH4 than what is normal ... BH4 is a required cofactor for the conversion of l-tyrosine to l-dopa. I truly believe that the combination of these 2 gene mutations plus chronic stress played a significant role in her development of PD. I am currently trying an approach where we target BH4 in an effort to increase her endogenous l-dopa production, since this alone could explain her reduced l-dopa levels.

Lindylanka, if you have done the 23andme genetic testing, it would be interesting to see if you have any strong (+/+) mutations in any of the B12 and/or folate related genes. If you are not taking the active forms (methyl-B12, methyl-folate) , you may want to consider trying them, especially if you know from your genetic results that you have mutations in the folate/B12 cycles. Also, you can get your methylmalonic acid (MMA) checked through a urine organic metabolite test, which my mom is currently awaiting results for. Finally, for the leg pains, have you checked your potassium levels? It may be worth looking into?