Mucuna Pruriens Combined with Carbidopa in Parkinson’s Disease: A Case Report

Abstract

We present a 48-year-old woman with Parkinson’s disease in whom carbidopa was added to Mucuna pruriens, resulting in marked motor improvement (documented on video and using MDS-UPDRS motor scores). This case report shows that adding a dopa-decarboxylase inhibitor (DDCI) to Mucuna pruriens could fit well in a personalized approach for patients who are reluctant to start levodopa. Meanwhile, larger trials with a longer follow-up are needed to establish the true effects and tolerability of Mucuna pruriens plus a DDCI.

INTRODUCTION

We encounter many persons with Parkinson’s disease (PD) who are reluctant to start dopaminergic medication, especially in early disease stages. Arguments include fear of response fluctuations and a personal preference for alternative treatments or natural products [1]. Such patients may choose Mucuna pruriens (MP) as an alternative to levodopa. MP is a levodopa-containing leguminous plant that grows in (sub)tropical areas worldwide [2]. Randomized clinical studies suggest that MP is as effective as levodopa for improving motor symptoms, with a favorable safety profile [3, 4]. However, similar to medicinal levodopa, the efficacy of MP may be suboptimal without adding a dopa-decarboxylase inhibitor (DDCI). Here, we present a video-documented patient in whom carbidopa was added to MP, leading to marked motor improvement.

CASE DESCRIPTION

In March 2018, we saw a 48-year-old woman with PD for a second opinion. In 2013, she had developed a tremor of the right arm and leg. She later developed increasing and debilitating problems during activities of daily living, including difficulties writing, cooking and eating. She also developed painful cramps in the right foot and an insecure gait, but without falls. For several years, her sole (self-prescribed) treatment consisted of MP 800 mg four times daily, containing approximately 160 mg levodopa/day, [5] which is a relatively low dose compared to earlier MP studies [3, 6]. She experienced only limited therapeutic benefits, not alleviating her increasing disability. Nevertheless, she insisted on continuing MP instead of initiating medicinal levodopa, mainly because she had experienced considerable benefits of using MP during the first years of the disease, and also because she presumed to experience benefits of other potentially effective compounds contained within MP. However, because her symptoms were progressing, and because she was not wholly against using synthetic medications, she did agree to add synthetic carbidopa (25 mg three times/day), aiming to increase cerebral dopamine concentrations. Yet, we should emphasize that ‘hardliners’ among the patients who wish to restrict their entire treatment to purely natural products will also reject the use of carbidopa, which means that for them the solution presented here would not work. Six weeks later, her complaints had improved markedly (Supplementary Video). Scores on the MDS-UPDRS part III on medication had improved from 37 (before carbidopa) to 24 (with carbidopa). The painful cramps were less, gait had improved considerably, she no longer felt unstable and fine motor skills were markedly better. Tremor was no longer bothersome in daily life. She experienced no side effects and was eager to continue treatment.

DISCUSSION

The patient presented here showed a marked improvement in motor symptoms after adding a DDCI (carbidopa) to MP, with a total improvement of 13 points on the MDS-UPDRS part III. This striking improvement is reminiscent of what was observed during the studies performed in the early 1970s when DDCIs were first added to levodopa, which led to a more rapid clinical improvement, a greater degree of improvement, worse dyskinesias (again suggesting greater efficacy) and the need of a much smaller dose of levodopa to reach maximum benefit [7–10]. When compared to trials of pharmacotherapy or deep brain stimulation (DBS) for PD, an improvement of 13 points it is a large effect. In a 42-week randomized controlled trial, patients receiving a daily dose of 187.5 mg of levodopa/carbidopa worsened 1.4 points on the MDS-UPDRS part III, while the placebo group worsened 5.2 points (total difference 3.8 points) [11]. However, these patients were all in early disease stages, with no expected need for dopaminergic medication in the upcoming two years, which may partially account for the relatively small treatment effect. In another randomized controlled trial that compared DBS to optimal oral pharmacotherapy, mean UPDRS-III scores improved by 19.6 points for DBS patients compared to 9.5 points for controls [12].

Our findings should be interpreted with caution. The large improvement may partially result from a placebo effect, which is particularly pronounced in PD [13]. Also, MP may not offer a long-term solution for all patients due to low tolerability. Our patient tolerated MP well, both before and after introduction of carbidopa, but this may not apply to all patients. A recent randomized crossover study evaluated tolerability for daily intake of MP versus levodopa/carbidopa. Here, MP was associated with reduced tolerability, due to gastrointestinal side-effects (21%) or progressive worsening of motor performance (29%) [6]. Adding a DDCI to MP may improve tolerability, because less levodopa is metabolized peripherally. On the other hand, another trial also showed that dyskinesias were less pronounced for MP compared to levodopa [3]; which could help to promote patients’ acceptance of MP as symptomatic treatment.

The main importance of this report lies in the fact that it is not rare for PD patients to resist using levodopa and to resort to monotherapy with MP. We have seen many patients who experienced unnecessary and avoidable disability, presumably because taking MP without a DDCI is not a rational treatment. Importantly, here we chose to add carbidopa to MP instead of increasing the dose of MP alone, because the present levodopa dose was already 160 mg (i.e. largely comparable to the effective dose used in earlier trials) [11] and we aimed to increase the bioavailability of the levodopa already contained within her MP dose. If this would have been insufficiently effective, the second step would have been to increase the dose of MP, as one would do when prescribing regular levodopa/carbidopa formulations.

One might rightly argue that these patients should be persuaded to start on regular levodopa with a DDCI. However, a surprisingly large group of our patients insists on continuing MP, which they consider a form of alternative medication because of its aura as a natural product. In this time and era of personalized medicine, it is important to respect each patient’s own preferences, yet also adhere to a rational treatment regime. Therefore, when discussing the possible use of MP with a patient, it is important to provide proper information and to be cautious about the expected effects, emphasizing for example that MP contains the same levodopa as regular pharmaceutical products, but with the notable disadvantage that the exact quantification of the levodopa dose can vary when using MP. Our findings suggest that adding a DDCI to MP could fit well into a personalized approach for patients who are reluctant to start levodopa. Meanwhile, larger trials with a longer follow-up are needed to establish the true effects and tolerability of MP plus a DDCI.

CONFLICT OF INTEREST

The authors have no conflict of interest to report.