Levodopa, vitamins, ageing and the neuropathy of Parkinson's disease

J Neurol. 2013 Nov;260(11):2844-8. doi: 10.1007/s00415-013-7079-8. Epub 2013 Aug 30.


Higher prevalence of neuropathy has been described in patients with Parkinson's disease (PD) in comparison with age and gender-matched controls. The cause of neuropathy may be levodopa-induced impairment of vitamin B12 metabolism, suggesting levodopa-naïve subjects should be unaffected. There may, however, be other yet unidentified determinants of neuropathy in PD. We screened 33 consecutive levodopa-naïve PD patients for neuropathy. Demographics, vitamin B12 and folate levels were studied. Findings were analyzed in the light of our previous available data on levodopa-treated PD patients. Four of 33 (12.1 %) levodopa-naïve PD patients were diagnosed with neuropathy. This compared to 13/36 (36.1 %) previously evaluated levodopa-treated patients (p = 0.027) and 3/37 controls (p = 0.7). Analysis of our whole PD cohort consisting of a total of 70 subjects, including levodopa-naïve and levodopa-treated patients, revealed that neuropathy correlated with use of levodopa (p = 0.041), cumulative levodopa exposure (p = 0.046), age at time of study (p = 0.005) and serum folate levels <10 μg/L (p = 0.003). There was no association of neuropathy with PD duration. Multivariate regression analysis showed that neuropathy was only independently associated with age (p = 0.016) and serum folate levels <10 μg/L (p = 0.012). We conclude that this study confirms the roles of levodopa usage and cumulative levodopa exposure in the neuropathy of PD. However, the effects of levodopa only appear contributory and are surpassed by age and lower folate levels. In view of the independent implication of lower folate levels, the need for preventative/protective supplementation including folate in addition to vitamin B12, probably irrespective of levodopa use, may deserve consideration in patients with PD.

MeSH terms

  • Adult
  • Aged
  • Aging*
  • Antiparkinson Agents / adverse effects*
  • Cross-Sectional Studies
  • Female
  • Folic Acid / blood*
  • Humans
  • Levodopa / adverse effects*
  • Male
  • Middle Aged
  • Nervous System Diseases / chemically induced*
  • Parkinson Disease* / blood
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / epidemiology
  • Vitamin B 12 / blood*


  • Antiparkinson Agents
  • Levodopa
  • Folic Acid
  • Vitamin B 12