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

Abstract

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.

Polyneuropathy associated with duodenal infusion of levodopa in Parkinson's disease: features, pathogenesis and management

“…The prevalence of B 12 deficiency increases with age 29. This may explain the positive correlation between PNP and age in patients with PD 4 5…”

Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy

“…Levodopa therapy has been identified to be a risk factor for neuropathy (Mancini et al., 2014; Rajabally & Martey, 2013; Toth et al., 2008); however, dose dependency has not yet been studied systematically: one recent study found that IPD patients with neuropathy had an LDD of 1,180 mg, while those without neuropathy had an LDD of 775 mg (Mancini et al., 2014), and like in our study, there were no differences regarding age, gender, and H&Y stage. Our sample, however, had higher LDDs and longer disease durations and therefore very likely a higher exposure to levodopa.…”

“…Cobalamin deficiency as a potential cause of neuropathy in IPD has been investigated extensively, but with conflicting results: in levodopa‐treated IPD patients, cobalamin has been shown to be lower in those with neuropathy than in those without it (Ceravolo et al., 2013; Mancini et al., 2014); some researchers have found an association between cobalamin levels and levodopa doses (Rajabally & Martey, 2013; Toth et al., 2010), but this finding could not be confirmed by others (Mancini et al., 2014). Also folate deficiency (Rajabally & Martey, 2013) and levodopa itself, especially LCIG and its ingredients or its way of resorption (Jugel et al., 2013), have been suspected to be involved in the development of neuropathy in IPD.…”

“…Also folate deficiency (Rajabally & Martey, 2013) and levodopa itself, especially LCIG and its ingredients or its way of resorption (Jugel et al., 2013), have been suspected to be involved in the development of neuropathy in IPD.…”

Preventing and Slowing the Progression of Parkinson's: A Clinical Conversation with Laurie Mischley, ND, MPH, PhD, and Robert Rountree, MD

“…Levodopa interferes with folic acid metabolism and raises homocysteine. 26 The more levodopa someone is on, the higher the homocysteine level, which increases the risk of dementia. This is especially true in patients with Parkinson's.…”