TABLE 5.

Overview of studies investigating the effect of other dietary interventions on levodopa treatment in patients with Parkinson's Disease¹

First author, year (reference); study design	Patient and levodopa characteristics	Dietary intervention	Outcome measures	Results	Risk of bias
Fiber
Astarloa, 1992 (56); pre/post intervention	n = 19, constipation Mean ± SE age = 67.3 ± 1.70 y H&Y = II-III Mean ± SE disease duration = 5.10 ± 0.94 y Mean ± SE disease duration = 5.10 ± 0.94 y Levodopa use with different adjuvants Dose = usual daily dose	DRIF (28 g/d fiber) for 2 mo	-Plasma concentrations of levodopa and 3-OMD -Parkinson (motor) disability (UPDRS, upper extremities coordination, gait) -Constipation (bowel movements and feces consistency)	-Compared with baseline, DRIF increased levodopa concentrations (953.8 vs. 1266.6 ng/mL, P = 0.002) and reduced 3-OMD concentrations (5786.8 vs. 5303.1 ng/mL, P = 0.034) -Compared with baseline, DRIF reduced motor disability (UPDRS; 18 vs. 11 points, P < 0.001) -DRIF caused borderline significant improvement in upper extremities coordination (P < 0.059) and gait (P < 0.050) -DRIF reduces constipation (P < 0.001)	Low
Fernandez, 2014 (57); randomized double-blind crossover intervention	n = 18 Mean ± SE age = 69.8 ± 4.2 y Mean ± SE disease duration = 1.3 ± 0.5 y H&Y = — Levodopa/carbidopa use Dose = usual daily dose	Plantago ovata husk (3.5 mg), in 200 mL water 3×/d or placebo before levodopa; 2 × 14-d intervention, 7 d wash-out	-Levodopa pharmacokinetics (Cmax, Tmax, and AUC) -Number of peaks in levodopa concentration, following single dose	-No significant differences in Cmax, Tmax, AUC -Plantago ovata husk treatment reduced number of concentration peaks: at baseline/placebo/fiber, the number of patients with multiple peaks was 8/9/2	Low
Caffeine
Deleu, 2006 (58); randomized double-blind crossover	n = 12 Mean ± SE age = 61 ± 9 y Mean ± SE disease duration = 6.3 ± 3.1 y H&Y = I-III Levodopa/carbidopa use Dose (±SE) = 604 ± 127 mg/d	Caffeine (200 mg) or placebo 15 min before single tablet of levodopa/carbidopa (250/25 mg); 4 d in total, 2-d intervention, 48-h wash-out	-Levodopa pharmacokinetics (Cmax, Tmax, and AUC) -Motor performance: walking speed (onset + magnitude), finger-tapping speed (onset + magnitude)-4-point dyskinesia scale	-Shorter Tmax with caffeine versus placebo (60 vs. 90 min, P = 0.003), no differences in Cmax and AUC -Comparing caffeine versus placebo, shorter walking onset (30 vs. 60 min, P = 0.03), higher walking magnitude (average increase of 44%, P < 0.0001), shorter tapping onset (30 vs. 90 min, P = 0.009), no difference in tapping magnitude -No difference in dyskinesia scores	Low
Soybeans
Nagashima, 2016 (59); crossover intervention	n = 7, dyskinesia and wearing-off phenomena Mean ± SE age = 67.1 ± 7.9 y Mean ± SE disease duration = 10.7 ± 3.5 y H&Y (±SE) = 3.0 ± 0.6 Levodopa/carbidopa use with different adjuvants Dose = 378.6 mg/d	Tablet of levodopa/carbidopa in combination with 11 g ground soybeans versus tablet levodopa/carbidopa without soybeans; 3-h intervention, 1-wk wash-out	-Plasma concentrations of levodopa and 3-OMD -On-periods (minutes/3 h, self-reported) -Dyskinesia severity (mAIMS)	-Comparing levodopa AUC and 3-OMD AUC without versus with soybeans, no differences; comparing EMM (adjusted for covariates) with soybeans versus without soybeans, decrease in 3-OMD (317.0 vs. 374.6 ng/mL, P = 0.03) -Longer on-periods with soy consumption (80% increase, P = 0.028) -EMM of dyskinesia severity lower with soy (1.9) versus without soy (3.9, P < 0.001)	Low
Ketogenic diet
Elbarbry, 2019 (45); pre/post intervention	n = 4 Age = — Disease duration = — H&Y = II-III Levodopa/carbidopa use Dose = —	Ketogenic diet (80% fat, 15% protein, 5% carbohydrates) for 12 wk	Levodopa pharmacokinetics (Cmax, Tmax, and AUC)	Compared with baseline, no changes in Cmax, Tmax, and AUC	Moderate

¹Cmax, maximum concentration; DRIF, diet rich in insoluble fiber; EMM, estimated marginal means; H&Y, Hoehn and Yarh stage; (m)AIMS, (modified) Abnormal Involuntary Movement Scale; Tmax, time to reach maximum concentration; UPDRS, Unified Parkinson's Disease Rating Scale; 3-OMD, 3-O-methyldopa.