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A balanced carbohydrate: protein diet in the management of Parkinson’s disease

LevaDopa to someone with PD is like petrol is to a car, each needs the other to move.
Put more in and they travel further, run dry and they stop.
As the last few drops of petrol trickle through the engine, the car lurches to a stop.
As the remains of the levodopa are used up by the body, it becomes difficult to move or you shake more.
The problem is taking more levodopa is not the same as putting more fuel in the tank.. the levodopa has to pass through the stomach into the small intestine before it passes into the blood stream, on its way to the brain. That takes time, about 30 minutes if the stomach is empty; depending on what and how much has been eaten it can be twice as long. So there you are waiting for some levodopa to reach the brain. The more fat in your meal, the slower the journey.

A balanced carbohydrate: protein diet in the management of Parkinson’s disease
Article abstract-Although restricting dietary protein is a proposed adjunct to
treating Parkinson’s disease (PD), the effect of carbohydrate consumption is
unknown. We measured plasma levodopa and large neutral amino acid (LNAA)
levels in nine PD patients treated with carbidopa/levodopa and different isocaloric
meals containing high protein-low carbohydrate, low protein-high carbohydrate,
and balanced 5 :1 carbohydrate: protein mixtures. We found that levodopa levels
increased significantly regardless of the type of diet, but that plasma LNAA levels
varied less and motor performance was superior after the balanced diet than after
the other two meals. We conclude that PD patients can consume nutritionally
adequate meals and still maintain a stable plasma levodopa: LNAA ratio.
NEUROLOGY 1991;41:1295-1297
E.M. Berry, MD, FRCP; J.H. Growdon, MD; J.J. Wurtman, PhD; B. Caballero, MD, PhD;
and R.J. Wurtman, MD
Levodopa, the principal drug used in the treatment of

Parkinson’s disease (PD), is a large neutral amino acid
(LNAA) whose passage across biological membranes
depends on the same system that transports other
LNAAs- including valine, leucine, isoleucine, tyrosine,
tryptophan, and phenylalanine.1 Although there may be
some interaction between levodopa and the LNAAs in
absorption across the intestinal mucosa, competition
with LNAAs at the blood-brain barrier limits
levodopa’s entry into the brain because of the lowKm of
this transport system. Two factors determine the
amount oflevodopa entering the brain: the plasma concentration
of levodopa and the summed concentrations
of the LNAAs. Clinical experiments confirming the
importance of the plasma levodopa: LNAA ratio in PD
showed that administration of LNAAs to PD patients
worsened motor symptoms that had been stabilized by
constant infusions of levodopa.2,3 Pincus and Barry4
suggested that plasma levels of LNAAs in PD patients
are better predictors of clinical responses to levodopa
than levodopa levels alone.
Soon after levodopa was introduced into clinical
practice, Mena and Cotzias5 proposed that dietary manipulations
could potentiate drug effects. Subsequently,
Pincus and Barry6 recommended a diet low in protein
content for restoring clinical benefit to PD patients who
had become unresponsive to levodopa and for minimizing
fluctuations in motor activity such as on-off phenomena
and end-of-dose loss of efficacy. Whether lowprotein
diets are efficacious in PD remains controversial6-
8;they are, however, widely known and publicized.
In chronic conditions such as PD, emphasis on protein
restriction may be dangerous as it may lead to protein
malnutrition. Furthermore, protein restriction may be
unnecessary because consumption of carbohydrates, by
eliciting insulin secretion, can also lower plasma LNAA
levels. We, therefore, undertook a study to determine
the effects on plasma levodopa and LNAA levels of
giving PD patients test diets that contained carbohydrate
and protein in various ratios. Dietary means of
maintaining predictable plasma levels of LNAAs
should enhance precision in titrating oral doses of
levodopa to achieve optimal clinical benefit.
Methods. The participants in this study were nine men with
PD. All signed an informed consent form approved by the
MIT Subcommittee on the Use of Humans as Experimental
Subjects. The patients had a mean age (SEM) of 60.6 years
(1.9) and weight of80.3 kg (3.9); their mean duration of illness
was 12.4 years (1.4), and the mean Hoehn and Yahr stage was
2.3 (0.2). All patients took a combination of carbidopa/
levodopa (Sinemet) with a mean levodopa dose of 1,000 mg/d
(range, 600 to 1,750 mg/d) in divided doses. Throughout the
study, patients received their usual dose of medication; all
took 100 mg of levodopa at 8 AMwith breakfast, and four
patients also required 100 mg on rising at 6 AM.
All patients were admitted to the MIT Clinical Research
Center for 3 consecutive days and each morning consumed
breakfasts of different composition but equivalent caloric
value (table 1). All patients received the three meals in a
random order. Blood samples were collected at 8 AMfrom an
indwelling venous catheter before breakfast and levodopa, and
again 1and 2 hours after ingesting carbidopa/levodopa and the
experimental breakfast. Blood was centrifuged, and the
plasma separated and frozen at -20°C until assay. Plasma
levodopa and LNAA levels were measured by high-performance
liquid chromatography; plasma tryptophan was measured
by a spectrofluorometric method.
Three clinical measures were used to monitor the behavioral
consequences of levodopa-diet interactions at baseline
and 1 and 2 hours after levodopa administration:
(1)Subjective assessment by the patient. Subjects rated their
motor state on a qualitative scale that extended from hypokinetic
and trembling through normal to hyperkinetic and dystonic. One
ofthe investigators (E.M.B.) who did not know the composition
of the diet examined each patient during the morning to determine
the presence of involuntary movements.
Table 1. Composition of the three different breakfast
meals*
Carbo-
Carbohydrate Protein Fat hydrate:protein
Diet (g) (g) (g) ratio
High protein
High carbohydrate
Balanced
24 (15)t
128 (SO)
107 (67)
SO(50) 25 (35)
6 (3) 12 (17)
20 (12) 15 (21)
0.3
21.3
5.4 .All meals contained approximately 640 calories.
t Percent composition in parentheses.
900
600
c:::Jlime 0
IZ2I after I hr
IS:SI alter 2 hr
<t
Z
-‘
600
500
CARBOHYDRATE BALANCED PROTEIN
Figure. Plasma LNAA levels (nmol/ml) after highcarbohydrate,
high-protein, and balanced
carbohydrate:protein meals. Bars indicate SEM. LNAA
levels 1 and 2 hours after all three meals were significantly
different from each other.
(2) Purdue Pegboard Test. The number of pegs placed in
the board by the right hand, by the left hand, and then bimanually
were counted during a 30-second period. The three
scores were summed; the greater the number of pegs, the better
the performance.
(3) Writing a standard nine-word sentence. The length of
the sentence and the time taken to write it were measured.
The data were analyzed by repeated measures analysis of
variance (ANOVA) using the SAS statistical software package
(SAS Institute Inc., Cary, NC). Alpha was set at 0.05.
Post-hoc testing by the Newman-Keuls test was performed
when the ANOVA was significant.
Results. Plasma amino acid levels. Fasting levels of
LNAAs and levodopa were similar on all 3 days and did
not differ significantly across patients. There was a significant
difference (p < 0.001) in the LNAA levels in response
to the different diets (figure). Mean LNAA levels
rose 24% after the high-protein meal, fell 18% after the
high-carbohydrate meal, and remained the same «3%
change) after the balanced diet. Post-hoc analyses showed
that the LNAA levels resulting from all three diets were
significantly different from each other at 1 and 2 hours.
Levodopa levels. Levels oflevodopa increased significantly
(p < 0.01) after carbidopa/levodopa administration
regardless of diet (table 2). There was a significant
diet by time interaction in the calculated plasma
levodopa: LNAA ratio (p = 0.038); the ratio was still
rising at 2 hours after a high-carbohydrate meal, steady
after the balanced meal, and had returned to baseline
value after the high-protein meal.
Clinical assessment. According to the subjective
scores, all patients felt undermedicated before breakfast
and all improved after levodopa/carbidopa treatment
regardless of the diet consumed. Nonetheless, five ofthe
nine patients reported worsening of parkinsonian
symptoms after the high-protein diet, and three of them
also experienced dyskinesias or increased restlessness
after the high-carbohydrate meal. After the balanced
meal, only one subject developed dyskinesias, although
another felt especially energized (“like Popeye after
spinach”). Of the nine patients, only two were unaffected
by the dietary manipulations.
Motor performance. There was a significant correla- .
Table 2. Mean plasma levodopa levels (nmol/ml) in
nine patients with PD before and after ingesting
carbidopa/levodopa with breakfasts of different
nutrient composition
Time
High
carbohydrate Balanced
High
protein
Beforemeal
After 1 hr
After 2 hrs
1.95 :t 0.67
3.38 :t 0.62
3.55 :t 0.84
1.82 :t 0.51
4.57 :t 0.96
2.35 :t 0.32
1.88 :t 0.56
3.45 :t 1.06
2.26 :t 0.59
Repeated measures ANOV A:
Diet:p = 0.75.
Time: p = 0.011.
Diet X time: p = 0.17.
tion between the patients’ subjective assessment of
treatment response and pegboard performance (r =
0.64, P = 0.0001) and also sentence length (r = 0.48, P
= 0.0001). The pegboard score differed according to the
type of breakfast eaten, with a significant diet by time
interaction (p = 0.028). With the balanced diet, performance
improved steadily over 2 hours, whereas performance
peaked at 1 hour and declined at 2 hours after
both the high-protein and high-carbohydrate meals. A
similar but nonsignificant trend was observed with an
increase in sentence length. Two hours after eating, as
sentence length increased, writing time decreased by
10% after the carbohydrate and balanced diets, but
increased by 5% after the protein meal. The
levodopa: LNAA ratio correlated significantly with
clinical performance on the pegboard test (r = 0.40,P =
0.001) and sentence length (r = O.:W,p = 0.006).
Discussion. This study indicates that in PD patients
receiving levodopa/carbidopa, plasma LNAA levels remain
stable for 2 hours after a balanced meal containing
a carbohydrate: protein ratio of 5: 1. Such a balanced
diet in the management of PD fulfills two requirements:
the diet is nutritionally complete, and it stabilizes plasma
LNAA levels for titrating levodopa dosages. An analogy
may be drawn from the treatment of diabetes in which the
optimal control of blood glucose depends on the timing
and nature of the diet as well as the dose and type of
insulin. Similarly, the management of PD should include
attention to a balanced diet as well as to the levodopa dose
and schedule. Prior recommendations for PD diets have
focused entirely on restricting protein consumption to 0.5
gjkg body weight/d5 or omitting protein at breakfast and
lunch and providing this nutrient only in the evening.6
The recommended daily allowance for protein is 0.75 to
0.8 gjkg body weight/d,9 and even this intake may be
inadequate in the elderly to prevent negative nitrogen
balance.tO Our data suggest that it is not necessary to
limit protein intake of patients with PD to achieve
stable levels of levodopa and LNAAs, and therefore a
predictable plasma levodopa: LNAA ratio. In susceptible
patients, consumption of meals containing carbohydrate,
but lacking sufficient protein, can cause signs’ of
levodopa toxicity (dyskinesias), probably because too
much drug suddenly enters the brain.8 When presented
in a ratio of 5: 1, the divergent effects of carbohydrate
—–
and protein consumption are balanced and the plasma
LNAA levels remain stable. Equally important for
chronic treatment, the balanced diet used in this study,
if consumed for the other meals, would provide sufficient
protein (60 gld, equivalent to 0.86 gjkg for a 70-kg
adult) to meet recommended daily requirements.9
The focus of our study was nutritional and biochemical;
additional research will be required in order to
explore the clinical consequences of the balanced carbohydrate:
protein diet in minimizing fluctuations in
motor activity. That performance on the pegboard test
after the balanced diet was superior than after either the
high-protein or high-carbohydrate meals is a preliminary
finding, but suggests that the balanced diet does not
worsen and may, in fact, enhance motor performance.
Acknowledgments
We wish to thank Elizabeth Campbell, RN, and Rita Tsay, RD, for
helping with the study protocol, Christine Bilmazes and Carol
Watkins for the amino acid determinations, and Raymond Gleason,
PhD, for the statistical analyses.
From the Department of Brain and Cognitive Sciences and the Clinical Research
Center, Massachusetts Institute of Technology. Cambridge. MA, and
the Department of Neurology, Massachuseits General Hospital, Boston, MA.
~ in part by a grant from the American Parkinson’s Iroease Foundation.
Received October 10, 1990.Aocept.edfor publication in final form Janwuy 18,199L
Address correspondence and reprint requests to Dr. John H. Growdon, Massachusetts
General Hospital, ACC 830, Boston, MA 02114.
References
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1984;310:483-488.
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in fluctuating parkinsonian patients. Neurology
1986;36:739-744.
4. Pincus JH, Barry KM. Plasma levels of amino acids correlate with
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1987;44:1006-1009.
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Reprinted from NEUROLOGY,Volume 41, Number 8, August 1991
@ Copyright 1991by EdgellCommunications,Inc.
Printed in U.S.A.
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July 4, 2014 - Posted by Chris | Nutrition