TABLE 3.
Overview of studies investigating the effect of dietary proteins 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 |
|---|---|---|---|---|---|
| Juncos, 1987 (48); crossover intervention | n = 6, motor fluctuationsMean ± SE age = 59 ± 2.5 yMean ± SE disease duration = 14 ± 2 yH&Y = III to VLevodopa/carbidopa useDose = usual daily dose | Single high-protein load (0.4 g protein/kg body weight, 33% above RDA for 1 meal) versus diet adhering to RDAFour-hour measurement after protein meal | -Plasma LNAA concentrations-Motor symptoms and dyskinesia severity (both measured with 4-point modified Colombia rating scale) | -Increased LNAA concentrations after high-protein load-High-protein load worsened motor response with mean increase of 1.7 points.-High-protein load reduced dyskinesia symptoms with mean reduction of 2.3 points-No effect of RDA meals on motor responses | Low |
| Pincus, 1987 (49); crossover intervention | n = 7, motor fluctuations Mean age (range) = 56 (46–63) y Mean disease duration (range) = 16 (8–22) y H&Y = — Levodopa/carbidopa use Dose (range) = 1243 (400–2800) mg/d | PRD (7 g protein until supper) versus high-protein diet (160 g protein until supper), both combined with normal supper meal (25 g protein); intervention diets on consecutive days | -Plasma LNAA concentrations -Plasma levodopa concentrations-Motor disability: measured by NYUDS -Dyskinesia severity (AIMS) | -Higher LNAA concentrations during high-protein diet versus PRD (1439 vs. 467 μmol/L; change, 71%; P = 0.005) -Higher levodopa concentrations during high-protein diet versus PRD (1.15 vs. 0.80 μmol/L; change, 30%; P = 0.025) -Lower motor disability (better motor performance) on PRD versus high-protein diet (12 vs. 31 points; change, 61%; P = 0.01)-Higher dyskinesia severity on PRD versus high-protein diet (16 vs. 2 points; change, 800%; P = 0.005) | Low |
| Frankel, 1989 (42); pre/post intervention | n = 4, levodopa-related motor fluctuations Mean age (range) = 65 (59–73) y Mean disease duration (range) = 10 (8–15) y H&Y = — Duodenal levodopa infusion Dose = 50 mg bolus, then continue infusion of 50 mg/h | Levodopa infusion for 7.5 h; single oral high-protein drink (60 mg protein) after 4-h infusion | -Plasma concentrations LNAA -Plasma concentrations levodopa -Motor performance: finger-tapping speed (taps/30 s) and walking speed (time/12 m) | -Increased LNAA concentrations after protein drink versus baseline (1913 vs. 1106 μmol/L; change, 72%) -Relatively unaltered levodopa concentrations after protein drink versus baseline (7.5 vs. 6.5 μmol/L; change, 15%) -Slower tapping speed (39 vs. 55 taps; change, 29%) and walking speed (14 vs. 10 s; change, 40%) after protein drink versus baseline | Moderate |
| Berry, 1991 (43); randomized crossover intervention | n = 9 Mean ± SE age = 60.6 ± 1.9 y Mean ± SE disease duration = 12.4 ± 1.4 y H&Y = 2.3 ± 0.2 Levodopa/carbidopa use Dose = 1000 mg/d | Together with levodopa dose, breakfast of “high-protein/low-carb” or “high-carb/low-protein” or balanced carb/protein (5/1) Interventions on 3 consecutive days, overnight wash-out | -Plasma concentrations LNAA -Plasma concentrations levodopa -Subjective motor assessment -Purdue pegboard test -Writing speed test | -Compared with baseline, LNAA concentrations increased after high protein (change, 24%), decreased after high carbohydrate (change, 18%) and was unaltered after balanced breakfast (change, 3%) -Increase in levodopa concentrations (% change from baseline), respectively, 1 and 2 h after high-protein (151%, 29%), high-carb (73%, 82%), and balanced breakfast (83%, 20%) -5 of 9 patients worse subjective motor assessment after high-protein, 3 of 9 worse dyskinesias after high-carb, 1 of 9 worse dyskinesia after balanced breakfast -Pegboard motor performance: steady increase 2 h after balanced breakfast, peak after 1 h, and decline after 2 h in high-protein and high-carb breakfast -No differences in writing time | Moderate |
| Bracco, 1991 (50); pre/post intervention | n = 16, motor fluctuations Mean age (range) = 65 (53–75) y Mean disease duration (range) = 9 (3–14) y H&Y = II-IV Levodopa/carbidopa use with different adjuvants Dose (range) = 625 (375–1000) mg/d | PRD (0.8 g protein/kg body weight, no protein before supper); evaluation at day 7 and 10, follow-up 1–12 mo | -Motor disability: measured by NYURS | -Lower motor disability (better motor performance) while on PRD (23 points) compared with baseline (34 points; P < 0.01) -5 of 16 patients: motor performance improved >20% -11 of 16 patients: motor performance improved up to 12% -3 of 16 patients developed dyskinesias | Low |
| Karstaedt, 1992 (46); crossover intervention | n = 43, with motor fluctuations Mean ± SE age = 69.3 ± 1.5 y Mean ± SE disease duration = 13.7 ± 1.0 y H&Y = — Levodopa/carbidopa use Dose = 839 mg/d | PRD (7 g protein before supper) versus normal hospital diet (protein content unknown) for 2–3 wk | -Motor disability: measured by NYUDS -Average “on” time (% of day) -Walking time 12 m back and forth | -Mean worst disability score lower during PRD (18.7 points) versus normal diet (31.4 points; change, 40.4%; P < 0.01) -On-time during PRD (76%) significantly higher compared with normal diet (17%; P < 0.01) -Faster walking time on PRD (6.3 s) compared with normal diet (16.0 s; P < 0.05) | Moderate |
| Karstaedt, 1993 (51); double-blind, placebo- controlled crossover | n = 18, motor fluctuations on PRD Mean ± SE age = 65.4 ± 2.0 y Mean ± SE disease duration = 11.9 ± 1.7 y H&Y = — Levodopa/carbidopa use Dose = usual daily dose | Single dose of aspartame (600 mg or 1200 mg) or placebo, 2 d intervention, wash-out overnight | -Motor disability: measured by NYUDS -Dyskinesia severity (AIMS) -Plasma levodopa concentrations -Walking speed | -No significant differences between aspartame (600 mg or 1200 mg) or placebo | Moderate |
| Simon, 2004 (39); crossover intervention | n = 20, advanced PD with motor fluctuations Mean ± SE age = 60 ± 10 y Mean disease duration = 10 y H&Y = II-IIII Levodopa use with different adjuvants Dose (± SE) = 213.7 ± 93.7 mg/d | Low-protein breakfast in the morning (7.6 g protein) vs. normal-protein lunch in the afternoon (38.7 g protein) | -Levodopa pharmacokinetics (Cmax, Tmax, AUC) | -Significant increase in AUC during normal-protein lunch (4736 μg/L ⋅ h) versus low-protein breakfast (3187 μg/L ⋅ h; P < 0.001) -After baseline corrections, no significant difference between morning and noon for Cmax, Tmax, and AUC -Carryover effect from morning levodopa concentrations | High |
| Barichella, 2006 (52); randomized single-blind crossover | n = 21, motor fluctuations Mean ± SE age = 60.6 ± 7.6 y Mean ± SE disease duration = 11.5 ± 4.3 y H&Y = II-III Levodopa use with different adjuvants Dose (± SE) = 567.5 ± 226.4 mg/d | PRD (15% protein intake in before supper) using LPP or balanced diet (60% protein intake before supper); both diets contain 0.8 g protein/kg body weight. 2 × 2 mo intervention, 2 mo wash-out | -On/off-periods (minutes/24 h, self-report) -Subjective improvement in postprandial motor blocks (GCI) | -Compared with balanced diet, PRD reduced total off-periods (271 vs. 164 min; P < 0.0001) and postprandial off-periods (79 vs. 49 minutes; P < 0.0001) -Compared with balanced diet, PRD versus prolonged total on-period (738 vs. 852 min; P < 0.0001) and postprandial on-periods (220 vs. 250 min; P < 0.0001) -Subjective improvement in 50% of patients | Low |
| Cucca, 2015 (44); randomized, double-blind, placebo-controlled trial | n = 22, fluctuating response to PRD Mean ± SE age both groups2 = 74 ± 3 y Mean ± SE disease duration both groups2 = 5.8 ± 1.5 y H&Y = — Levodopa use Dose = — | AA supplementation (2 × 8 g minimum of 1 h before levodopa) or placebo for 6 mo | -Oxidative stress, measured by ratio of GSH:GSSG -On/off motor periods | -Compared with baseline, AA supplementation decreased GSSG (5.2 vs. 2.4 μmol/L; P = 0.04) -No significant change in GSG:GSSG from baseline or placebo -No alterations on/off periods | Moderate |
1
—, results not available; AA, amino acid; AIMS, Abnormal Involuntary Movement Scale; Cmax, maximum concentration; GCI, global clinical impression; GSH, reduced form of glutathione; GSSG, oxidized form of glutathione; H&Y, Hoehn and Yarh stage; LNAA, large neutral amino acid; LPP, low-protein products; NYUDS, New York University Disability Scale; NYURS, New York University Rating Scale; PRD, protein redistribution diet; Tmax, time to reach maximum concentration; UPDRS, Unified Parkinson's Disease Rating Scale.
2
Age (intervention) = 74 ± 1 y, Disease duration (intervention) = 5.6 ± 1.5 y, Age (placebo) = 74 ± 4 y, Disease duration (placebo) = 6.0 ± 1.4 y.