Motor fluctuations due to interaction between dietary protein and levodopa in Parkinson's disease

Abstract

Background: The modulation of levodopa transport across the blood brain barrier by large neutral amino acids is well documented. Protein limitation and protein redistribution diets may improve motor fluctuations in patients with Parkinson's disease but the pharmacokinetics and pharmacodynamics of levodopa and amino acids are highly variable.

Methods: Clinical records of 1037 Parkinson's disease patients were analyzed to determine the proportion of patients with motor fluctuations related to protein interaction with levodopa. Motor fluctuations due to protein interaction with levodopa were defined as dietary protein being associated with (i) longer time to levodopa effectiveness, (ii) reduced benefit or duration of benefit, (iii) dose failures or (iv) earlier wearing off from a previously effective dose. Dose failures, sudden, painful or behavioral wearing-off periods, gait freezing, nausea, hallucinations, orthostasis, and dyskinesias were taken as markers of motor fluctuations, disease severity, and levodopa side effects potentially influenced by protein.

Results: 5.9 % of Parkinson's disease patients on levodopa, and 12.4 % with motor fluctuations on levodopa correlated their fluctuations with the relative timing of levodopa and protein intake. These patients were younger at disease onset, had worse motor fluctuations and had a higher incidence of family members with Parkinson's disease. Early wearing off or decreased dose efficacy were most commonly associated with protein interaction. 60 % of patients who modified their diets had weight loss.

Conclusions: This study suggests that clinically significant protein interaction with levodopa may occur mostly in a subset of Parkinson's disease patients with earlier disease onset and those with familial disease.

Keywords: Levodopa; Motor fluctuations; Parkinson disease; Protein effect.

Fig. 1

General characteristics of all patients who exhibited protein interaction with levodopa a Age at motor onset, b duration of disease, c maximal daily levodopa dose, d years on levodopa, e percentage of patients on a dopamine agonist and f percentage with first or second degree relative with parkinsonism. (PIL; black bars) compared to those that did not (no-PIL: all; white bars) and subgroups of PIL patients with motor fluctuations (no-PIL:mot-fluct; gradient bars) and no-PIL patients matched for disease-duration (no-PIL: dis-dur; light gray bars) and age-at-motor-onset (no-PIL: age-ons; dark gray bars). The numbers of patients represented in each graph are inset. P values represent results of the chi-square or Mann–Whitney test comparing each no-PIL group to the PIL group. Legend: PIL: protein interaction with levodopa, no-PIL: no protein interaction with levodopa

Fig. 2

a Motor and non-motor characteristics of all patients (black bars: PIL, white bars: no-PIL: all) and subgroups of no-PIL patients with motor fluctuations (no-PIL: mot-fluct; gradient bars), or matched for disease-duration (no-PIL:dis-dur; light gray bars) or age-at-motor-onset (no-PIL: age-ons; dark gray bars). b Characteristics of motor fluctuations in PIL patients compared to those with motor fluctuations in the no-PIL groups. P values represent results of the chi-square or Mann–Whitney test comparing each no-PIL group to the PIL group. Legend: PIL: protein interaction with levodopa, no-PIL: no protein interaction with levodopa, motor fluct: motor fluctuations, behav. OFFs: behavioral OFFs, FOG: freezing of gait, dysk: dyskinesias, ortho.:orthostasis, halluc.: hallucinations