Does dietary protein reduce levodopa absorption?

Short answer: No. High-protein meals may interfere with effectiveness of levodopa, for some patients, by some other mechanism.

Longer answer: Patients are frequently counseled to avoid taking levodopa after protein-heavy meals, based on the theory that protein interferes with levodopa absorption in the digestive system. At a molecular level, levodopa is absorbed by a membrane transporter, LAT1, which is also used to take up hydrophobic amino acids, including tyrosine, which is chemically very similar to levodopa. So there is a plausible rationale for this advice, as well as several empirical studies with data suggesting protein intake can dramatically delay levodopa absorption, and somewhat reduce the total amount absorbed. A figure from one such study is shown below.

Figure from Murata, M. J Neurol (2006) 253(Suppl 3): iii47. https://doi.org/10.1007/s00415-006-3009-3.

Other, arguably more rigorous, studies have cast significant doubt on this theory, such as the one below, which shows no significant impact of protein consumption.

Figure from Robertson, D. , Higginson, I. , Macklin, B. , Renwick, A. , Waller, D. and George, C. (1991), The influence of protein containing meals on the pharmacokinetics of levodopa in healthy volunteers.. British Journal of Clinical Pharmacology, 31: 413-417. doi:10.1111/j.1365-2125.1991.tb05555.x

In fact, multiple studies have shown increased levodopa levels in blood after protein consumption. The various studies differ in terms of the amount of protein, number and age of patients, and other parameters, making it difficult to sort out the reasons for the different conclusions. The overall balance of evidence, however, suggests little to no effect of protein consumption on levodopa absorption.

That does not, however, necessarily imply that the timing of levodopa doses with respect to protein-rich meals is irrelevant to Parkinson’s patients. Some of the same studies showing no significant impact of protein on levodopa levels in blood did in fact show some impact on drug efficacy for managing Parkinson’s disease symptoms. That is, dietary protein consumption could impact levodopa through some mechanism other than by reducing absorption; some authors have speculated that competition between levodopa and dietary amino acids could be happening at the blood-brain barrier, rather than in the gut. It remains unclear, however, whether the impact of dietary protein on effectiveness of levodopa is universal or restricted to certain types of patients.