Dietary habits and eating behaviors significantly modulate drug disposition and clinical performance in Parkinson's diseaseDietary Habits Influence How Parkinson's Medications Work in the Body

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder managed primarily through pharmacological dopamine replacement therapies—including levodopa (L-DOPA), dopamine receptor agonists, MAO-B inhibitors, COMT inhibitors, and novel non-dopaminergic agents like adenosine A2A receptor antagonists. However, long-term pharmacotherapy faces major challenges such as motor fluctuations, levodopa-induced dyskinesias, erratic gastrointestinal absorption, and inter-individual response variability. This review systematically synthesizes how dietary habits, macronutrient compositions, dietary patterns (e.g., Western, Eastern, Japanese, Vegetarian, Mediterranean/MIND, Ketogenic), and eating behaviors (such as restrictive eating, compulsive binge eating, and irregular meal timing) serve as critical extrinsic modulators of drug disposition and clinical performance. Multi-dimensional biological mechanisms underpin these interactions: competitive inhibition at LAT1 transporters by dietary large neutral amino acids (LNAAs), food-induced alterations in gastric emptying and hepatic/intestinal enzyme activity (e.g., CYP3A4, CYP1A2, UGT), neuroinflammatory and oxidative stress modulation via nutrient choices, and microbiota–gut–brain axis (MGBA) dynamics involving gut barrier integrity, microbial short-chain fatty acid (SCFA) production, and local bacterial enzymatic degradation of L-DOPA. In real world clinical practice, the absence of precision nutrition frameworks, protein-redistribution diets, targeted chronotherapeutic meal scheduling, and multidisciplinary nutritional support substantially hinders the effective translation of basic pharmacokinetic insights. Consequently, patients frequently encounter formidable clinical challenges, including destabilized pharmacokinetics, recurrent motor complications, and the inability to effectively delay disease progression.