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The effect of daytime restriction of dietary protein on the nutrient intakes and efficacy of levodopa… Paré, Sara 1990

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THE EFFECT OF DAYTIME RESTRICTION OF DIETARY PROTEIN ON THE NUTRIENT INTAKES AND EFFICACY OF LEVODOPA THERAPY IN PARKINSON'S DISEASE by SARA PARE B.Sc. (Biology), Laval University, Quebec City, 1984 B.Sc. (Dietetics), Laval University, Quebec City, 1987 A THESIS' SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES DIVISION OF HUMAN NUTRITION SCHOOL OF FAMILY AND NUTRITIONAL SCIENCES We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA May 1990 © Sara Pare, 1990 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of f f tL lhW ftoCi Dm R Win A) ft/ S c t ' t X J C i S S The University of British Columbia Vancouver, Canada DE-6 (2/88) ABSTRACT P r e v i o u s c o n t r o l l e d s t u d i e s have shown t h a t severe daytime r e s t r i c t i o n of d i e t a r y p r o t e i n improves the e f f i c a c y of L-dopa and reduces response f l u c t u a t i o n s i n some P a r k i n s o n ' s d i s e a s e i n - p a t i e n t s . The main purpose of the p r e s e n t study was t o i n v e s t i g a t e the n u t r i t i o n a l adequacy of the r e s t r i c t e d p r o t e i n d i e t . Other o b j e c t i v e s were t o a s s e s s the p a t i e n t s ' a c c e p t a n c e of the d i e t and t o i d e n t i f y the p r a c t i c a l d i f f i c u l t i e s e n c o untered i n f o l l o w i n g the d i e t a t home. The e f f e c t of t h e r e s t r i c t e d p r o t e i n d i e t on the s u b j e c t s ' response t o levodopa was a l s o examined. S u b j e c t s were 11 f r e e - l i v i n g , o t h e r w i s e h e a l t h y P a r k i n s o n ' s d i s e a s e p a t i e n t s who s u f f e r e d from u n p r e d i c t a b l e response f l u c t u a t i o n s t o Sinemet (L-dopa c o n t a i n i n g m e d i c i n e ) . T h i s c o n d i t i o n i s . a l s o d e s c r i b e d as the " o n - o f f " phenomenon. They were c o u n s e l l e d t o consume a daytime r e s t r i c t e d p r o t e i n d i e t f o r 6 weeks (mean ± s.d. p r o t e i n i n t a k e b e f o r e e v e n i n g meal 12 + 2 g f o r females and 14 + 3 g f o r m a l e s ) . Food i n t a k e was u n r e s t r i c t e d from d i n n e r u n t i l bedtime, and s u b j e c t s were encouraged t o consume n u t r i e n t - d e n s e foods d u r i n g t h i s p e r i o d . The s u b j e c t s were r e q u i r e d t o complete a s e r i e s of t h r e e 6-day f o o d r e c o r d s and " o n - o f f " c h a r t s ( p r e - d i e t , d i e t week 2, d i e t week 6 ) . The " o n - o f f " c h a r t s i n d i c a t e d the d a i l y number of hours spent i n the "on" s t a t e (when m e d i c a t i o n i s e f f e c t i v e and p a r k i n s o n i a n symptoms a r e c o n t r o l l e d ) and i n the " o f f " s t a t e (when m e d i c a t i o n i s not e f f e c t i v e and symptoms a r e not w e l l c o n t r o l l e d ) . Hemoglobin, plasma albumin, p r e a l b u m i n and f e r r i t i n were measured b e f o r e and a f t e r the 6-week d i e t p e r i o d . S u b j e c t i v e e v a l u a t i o n q u e s t i o n n a i r e s were completed by a l l p a r t i c i p a n t s and t h e i r spouses or c a r e g i v e r s . R e s u l t s from d i e t a r y r e c o r d a n a l y s i s showed t h a t the r e s t r i c t e d p r o t e i n d i e t was a s s o c i a t e d w i t h s i g n i f i c a n t d e c r e a s e s i n t o t a l i n t a k e s of p r o t e i n , c a l c i u m , i r o n , magnesium, phosphorus, n i a c i n , r i b o f l a v i n , v i t a m i n B6 and p a n t o t h e n a t e , i n comparison t o " u s u a l " i n t a k e s . I n t a k e of energy, c a r b o h y d r a t e s , l i p i d s , p o t a s s i u m , t h i a m i n , f o l a c i n , and v i t a m i n s A, C and B12 d i d not change s i g n i f i c a n t l y . While on the r e s t r i c t e d p r o t e i n d i e t , o n l y c a l c i u m i n t a k e was s u b s t a n t i a l l y l e s s than the RNI. B i o c h e m i c a l measures of n u t r i t i o n a l s t a t u s were not s i g n i f i c a n t l y reduced. Mean body weight tended t o d e c r e a s e (p=.054) over the f i r s t 2 weeks and then s t a b i l i z e d u n t i l the end of the s t u d y p e r i o d . The r e s u l t s of the " o n - o f f " c h a r t s showed t h a t t h r e e of t h e e l e v e n s u b j e c t s s i g n i f i c a n t l y i n c r e a s e d t h e i r d a i l y time "on" w h i l e on the r e s t r i c t e d p r o t e i n d i e t . S u b j e c t i v e l y , s i x i n d i v i d u a l s noted an improvement i n daytime m o b i l i t y and i n d i c a t e d t h a t they would m a i n t a i n the d i e t f o r an i n d e f i n i t e p e r i o d of t i m e . Problems i d e n t i f i e d by the s u b j e c t s i n c l u d e d hunger p r i o r - ' t o the e v e n i n g meal and a l a c k of v a r i e t y i n f o o d c h o i c e s . These r e s u l t s show t h a t o t h e r w i s e h e a l t h y and m o t i v a t e d p a t i e n t s w i t h P a r k i n s o n ' s d i s e a s e can m a i n t a i n an adequate i n t a k e of energy, p r o t e i n , and most n u t r i e n t s w h i l e on th e daytime r e s t r i c t e d p r o t e i n d i e t . The d i e t appeared t o be r e l a t i v e l y w e l l t o l e r a t e d by p a t i e n t s who o b t a i n e d a s u b j e c t i v e b e n e f i t . I t i s s u g g e s t e d t h a t i n p a t i e n t s whose i i i regular diets are marginally adequate, the restricted protein diet might compromise nutrient intakes. Counselling by a registered dietitian is recommended for a l l patients who undertake this type of diet. iv TABLE OF CONTENTS A b s t r a c t i i T a b l e of C o n t e n t s v L i s t of T a b l e s v i i L i s t of F i g u r e s v i i i Acknowledgements i x I. I n t r o d u c t i o n 1 I I . Review of the l i t e r a t u r e 3 P a r k i n s o n ' s d i s e a s e , a b r i e f overview 3 L-dopa t h e r a p y and the " o n - o f f " phenomenon 4 The e f f e c t of d i e t a r y p r o t e i n on the e f f i c a c y of L-dopa 6 A p p l i c a t i o n of a r e s t r i c t e d p r o t e i n d i e t t o f r e e - l i v i n g i n d i v i d u a l s w i t h P a r k i n s o n ' s d i s e a s e 8 Assessment of p a r k i n s o n i a n d i s a b i l i t y ..10 Assessment of d i e t a r y s t a t u s 11 Assessment of p r o t e i n and i r o n s t a t u s 14 Serum albumin and p r e a l b u m i n 14 Hemoglobin and f e r r i t i n 15 Summary 16 I I I . E x p e r i m e n t a l d e s i g n and methods IV S c r e e n i n g and s e l e c t i o n of s u b j e c t s 17 P r o t o c o l 18 The d i e t a r y r e c o r d and the " o n - o f f " c h a r t 20 The r e s t r i c t e d p r o t e i n d i e t 23 A n t h r o p o m e t r i c measurements 24 B i o c h e m i c a l a n a l y s e s .24 Q u e s t i o n n a i r e s 25 Data t r a n s f o r m a t i o n and s t a t i s t i c a l a n a l y s e s 25 D i e t a r y r e c o r d s 25 "On-off" c h a r t s 27 B i o c h e m i c a l parameters 27 Body weight 28 Q u e s t i o n n a i r e s 28 L i m i t a t i o n s of the study 28 IV. R e s u l t s 30 S u b j e c t s ' c h a r a c t e r i s t i c s 30 Adequacy of the s u b j e c t s ' n u t r i e n t i n t a k e s r e l a t i v e t o the RNIS....32 Changes i n energy and n u t r i e n t i n t a k e s 32 v P e r c e n t time "on" ; 37 B i o c h e m i c a l a n a l y s e s 37 Body weight 40 S u b j e c t i v e e v a l u a t i o n s 40 S u b j e c t s ' p e r c e p t i o n s 40 Sup p o r t e r s ' p e r c e p t i o n s . . . . 44 V. D i s c u s s i o n 48 Energy and n u t r i e n t i n t a k e s p r i o r t o and d u r i n g the daytime r e s t r i c t e d p r o t e i n d i e t 49 Regular d i e t 49 R e s t r i c t e d p r o t e i n d i e t 50 E v a l u a t i o n of the v a l i d i t y of t h e 6-day r e c o r d method 52 E f f e c t of the r e s t r i c t e d p r o t e i n d i e t on body weight 53 E f f e c t of the r e s t r i c t e d p r o t e i n d i e t on parameters of p r o t e i n and i r o n s t a t u s 54 E f f e c t of t h e r e s t r i c t e d p r o t e i n d i e t on p e r c e n t time "on" 55 Comments on the a p p l i c a t i o n of t h e r e s t r i c t e d p r o t e i n d i e t t o f r e e - l i v i n g i n d i v i d u a l s 57 VI. C o n c l u s i o n 59 B i b l i ography 61 appendix 1. Recruitment l e t t e r t o s u b j e c t s 66 appendix 2. Consent form 68 appendix 3. M i n i - m e n t a l s t a t e e x a m i n a t i o n form 72 appendix 4. L e t t e r t o G e n e r a l P r a c t i t i o n e r 74 appendix 5. C e r t i f i c a t e of a p p r o v a l from the C l i n i c a l S c r e e n i n g Committee f o r Research and Other S t u d i e s I n v o l v i n g Human S u b j e c t s . 76 appendix 6. I n s t r u c t i o n s f o r k e e p i n g a s i x day f o o d r e c o r d 78 appendix 7. "On-off" c h a r t 84 appendix 8. G u i d e l i n e s f o r the r e s t r i c t e d p r o t e i n d i e t 86 appendix 9. P a t i e n t s ' q u e s t i o n n a i r e 94 appendix 10. S u p p o r t e r s ' q u e s t i o n n a i r e 97 v i LIST OF TABLES I . Age, a n t h r o p o m e t r i c d a t a and m e d i c a l c h a r a c t e r i s t i c s of the 11 s u b j e c t s 31 * I I . Mean d a i l y i n t a k e of energy and 15 n u t r i e n t s of the 11 s u b j e c t s a c c o r d i n g t o sex and d i e t 33 I I I . R e s u l t s of the r e p e a t e d measure ANOVA on the changes i n n u t r i e n t i n t a k e s over t h e t h r e e r e c o r d i n g p e r i o d s 36 IV. R e s u l t s from the one-way ANOVA on d a i l y p e r c e n t "on" time 38 V. B i o c h e m i c a l parameters i n male and female s u b j e c t s b e f o r e and a f t e r t h e s i x week r e s t r i c t e d p r o t e i n d i e t p e r i o d 39 VI. T o t a l s of m u l t i p l e c h o i c e answers c o l l e c t e d from p a t i e n t s ' q u e s t i o n n a i r e s 42 V I I . P a t i e n t s ' comments 43 V I I I . T o t a l s of m u l t i p l e c h o i c e answers c o l l e c t e d from s u p p o r t e r s ' q u e s t i o n n a i r e s .45 IX. S u p p o r t e r s ' comments 46 v i i LIST OF FIGURES Experimental protocol v i i i ACKNOWLEDGEMENTS I s i n c e r e l y thank my r e s e a r c h s u p e r v i s o r Dr. Susan B a r r f o r her e x c e l l e n t g uidance, c o n s t a n t support and e n d l e s s encouragement throughout t h e c o m p l e t i o n of t h i s t h e s i s . I am e x t r e m e l y g r a t e f u l t o Susan Ross who i n i t i a t e d the p r o j e c t and Susan Cain e f o r h a v i n g always been a v a i l a b l e d e s p i t e t h e i r h e c t i c s c h e d u l e s and f o r t h e i r i n v a l u a b l e h e l p w i t h a l l a s p e c t s of the study. S p e c i a l thanks t o Dr. L i n d a McCargar f o r her c o n s t a n t i n t e r e s t i n the p r o j e c t , support and a s s i s t a n c e . I g r a t e f u l l y thank Dr. L e i c h t e r and Dr. Caine f o r s e r v i n g on my committee. I acknowledge t h e generous c o l l a b o r a t i o n r e c e i v e d from JoAnne Douglas, Karen P o u l i n and K a r o l T r a v i s s i n the development of the d i e t e d u c a t i o n m a t e r i a l and I thank them a l l . I thank LIV-N-WELL D i s t r i b u t o r s L t d . (Richmond, B.C.) f o r k i n d l y s u p p l y i n g l o w - p r o t e i n p r o d u c t samples. I g i v e my thanks t o t h e N a t u r a l S c i e n c e s and E n g i n e e r i n g Research C o u n c i l of Canada f o r p r o v i d i n g a p o s t g r a d u a t e s c h o l a r s h i p and t o the U n i v e r s i t y H o s p i t a l F o u n d a t i o n f o r f u n d i n g the p r o j e c t . F i n a l l y , super s p e c i a l thanks t o the 11 s u b j e c t s and t h e i r s u p p o r t e r s f o r t h e i r e n t h u s i a s t i c p a r t i c i p a t i o n i n the study. i x I. INTRODUCTION Levodopa g i v e n i n a s s o c i a t i o n w i t h a p e r i p h e r a l dopa d e c a r b o x y l a s e i n h i b i t o r such as c a r b i d o p a (e.g. SINEMET), i s the most e f f e c t i v e drug f o r symptomatic treatment of P a r k i n s o n ' s d i s e a s e . However, p r o l o n g e d t h e r a p y i s a s s o c i a t e d w i t h the development of wide and u n p r e d i c t a b l e motor-response f l u c t u a t i o n s or the " o n - o f f " phenomenon, which l e a d s t o a c o n s i d e r a b l e i n c r e a s e i n d i s a b i l i t y . M e d i c a l approaches f o r o p t i m i z i n g c l i n i c a l management of f l u c t u a t i o n s have met w i t h o n l y l i m i t e d s u c c e s s (Lees 1989). C o n t r o l l e d s t u d i e s have shown t h a t severe daytime r e s t r i c t i o n of d i e t a r y p r o t e i n (<7g p r o t e i n p r i o r t o e v e n i n g meal) can reduce the f r e q u e n c y and d u r a t i o n of " o f f " p e r i o d s , t h e r e b y i m p r o v i n g m o b i l i t y ( T s u i et a l . 1989, P i n c u s and B a r r y 1987ab, 1988). D i e t a r y p r o t e i n r e s t r i c t i o n c o u l d t h e r e f o r e r e p r e s e n t a p o t e n t i a l l y u s e f u l a d j u n c t t o drug t h e r a p y f o r p a t i e n t s e x p e r i e n c i n g response f l u c t u a t i o n s . P r i o r t o s u p p o r t i n g such a r e s t r i c t i v e d i e t as p a r t of the c l i n i c a l management of the " o n - o f f " phenomenon, n u t r i t i o n a l and o t h e r p r a c t i c a l i m p l i c a t i o n s need t o be c o n s i d e r e d . In t h i s study e l e v e n f r e e - l i v i n g P a r k i n s o n ' s d i s e a s e p a t i e n t s s u f f e r i n g from u n p r e d i c t a b l e response f l u c t u a t i o n s t o levodopa underwent a daytime r e s t r i c t e d p r o t e i n d i e t f o r s i x weeks. The study was d e s i g n e d t o a s s e s s the p o t e n t i a l impact of daytime p r o t e i n r e s t r i c t i o n on energy and n u t r i e n t i n t a k e s and o t h e r f a c t o r s i n f l u e n c i n g the n u t r i t i o n a l s t a t u s of P a r k i n s o n ' s d i s e a s e p a t i e n t s . A d d i t i o n a l o b j e c t i v e s of t h i s 1 research project were to evaluate acceptance of the diet and to identify the difficulties encountered in following the diet at home. The effect of the diet on the efficacy of medication was also assessed. It was hypothesized that: 1) while consuming the experimental diet, average energy and nutrient intakes of the subjects would be similar to their "usual" intakes; 2) the experimental diet would not affect body weight; 3 ) the experimental diet would not affect protein and iron status, as assessed by serum prealbumin and ferrit in, respectively; 4) while consuming the experimental diet, some subjects would experience a significant increase in daily percentage of "on" hours. The following assumptions were made: 1) the subjects would adhere to the experimental diet for a period of six weeks; 2) food intake records would reflect the subjects' actual intakes; 3 ) "on-off" charts would reflect the actual proportion of time each subject spent in the "on" and in the "off" states; 4) a six week period would be long enough to induce changes in serum prealbumin and ferritin levels if the subjects' protein and iron intakes respectively, were inadequate; 5) the subjects' activity level would remain stable throughout the 8-week study period. 2 II. REVIEW OF THE LITERATURE The " o n - o f f " phenomenon i s a consequence of p r o l o n g e d levodopa t h e r a p y i n p a t i e n t s w i t h P a r k i n s o n ' s d i s e a s e . Severe daytime p r o t e i n r e s t r i c t i o n has been su g g e s t e d as a p o s s i b l e s t r a t e g y t o h e l p c o n t r o l motor-response f l u c t u a t i o n s . However, the p o t e n t i a l l o n g - t e r m n u t r i t i o n a l i m p l i c a t i o n s of such a d i e t have not y e t been i n v e s t i g a t e d . In t h i s c h a p t e r , a r e v i e w of the p e r t i n e n t l i t e r a t u r e i n the f o l l o w i n g t o p i c a r e a s w i l l be p r e s e n t e d : D e s c r i p t i o n of P a r k i n s o n ' s d i s e a s e ; levodopa t h e r a p y and the " o n - o f f " phenomenon; the e f f e c t of d i e t a r y p r o t e i n on t h e e f f i c a c y of l e v o dopa; and the a p p l i c a t i o n of a r e s t r i c t e d p r o t e i n d i e t t o f r e e - l i v i n g i n d i v i d u a l s w i t h P a r k i n s o n ' s d i s e a s e . A d d i t i o n a l s e c t i o n s w i l l a d d r e s s the i s s u e s of assessment of p a r k i n s o n i a n d i s a b i l i t y , t h e use of the w r i t t e n f o o d r e c o r d i n a s s e s s i n g d i e t a r y s t a t u s and the e v a l u a t i o n of p r o t e i n and i r o n s t a t u s . PARKINSON'S DISEASE, A BRIEF OVERVIEW P a r k i n s o n ' s d i s e a s e i s a n e u r o d e g e n e r a t i v e d i s o r d e r c h a r a c t e r i z e d by slowness and p o v e r t y of movement ( b r a d y k i n e s i a ) , muscular r i g i d i t y and r e s t i n g tremor. These c l i n i c a l symptoms are a t t r i b u t e d t o dopamine d e p l e t i o n i n a r e g i o n of the b r a i n t h a t c o n t r o l s movement, the s u b s t a n t i a n i g r a . Dopaminergic c e l l death of unknown e t i o l o g y i s a t the o r i g i n of the dopamine d e p l e t i o n . P a r k i n s o n ' s d i s e a s e u s u a l l y appears i n the l a t t e r decades of l i f e , between ages 50 and 70 ( M a r t t i l a 1987). In the USA, i t i s b e l i e v e d t o 3 a f f e c t one p e r c e n t of the p o p u l a t i o n over age 50 w i t h no d i f f e r e n c e i n i n c i d e n c e based on gender, a r e a of r e s i d e n c e , o c c u p a t i o n or s o c i a l s t a t u s ( D u v o i s i n 1984). L-DOPA THERAPY AND THE "ON-OFF" PHENOMENON The most e f f e c t i v e t h e r a p e u t i c agent a v a i l a b l e f o r symptomatic tre a t m e n t of P a r k i n s o n ' s d i s e a s e i s o r a l l y a d m i n i s t e r e d L-dopa ( l e v o d o p a ) . Levodopa i s t r a n s p o r t e d from plasma i n t o b r a i n by the s a t u r a b l e l a r g e n e u t r a l amino a c i d (LNAA) t r a n s p o r t system of the b l o o d -b r a i n - b a r r i e r . Once i n s i d e the b r a i n , i t i s taken up by i n t a c t nerve c e l l s and d e c a r b o x y l a t e d i n t o dopamine, t h e r e b y r e p l e n i s h i n g , a t l e a s t i n p a r t , the d e f i c i e n t s t o r e s . I n i t i a l l y , most P a r k i n s o n ' s d i s e a s e p a t i e n t s b e n e f i t from a c o n s t a n t and s t a b l e l o n g - d u r a t i o n r e sponse t o levodopa. In t h i s r e g a r d D u v o i s i n (1984) r e l a t e s : "Most p a t i e n t s a r e not aware of the e f f e c t of each i n d i v i d u a l dose. Nor ar e t h e y aware of any d e f i n i t e change i f t h e y miss a g i v e n dose." A f t e r a v a r i a b l e p e r i o d of time on c h r o n i c levodopa t h e r a p y , p a t i e n t s b e g i n t o e x p e r i e n c e motor-response f l u c t u a t i o n s . One t y p e of f l u c t u a t i o n i s c a l l e d the " w e a r i n g - o f f - e f f e c t " i n which the d u r a t i o n of e f f i c a c y of each dose becomes s h o r t e r , a l l o w i n g a g r a d u a l r e t u r n of p a r k i n s o n i a n symptoms b e f o r e the subsequent dose t a k e s e f f e c t (Klawns 1984). A more severe type of f l u c t u a t i o n i s d e s c r i b e d as t h e " o n - o f f " phenomenon i n which p a t i e n t s u n p r e d i c t a b l y e x h i b i t abrupt a l t e r a t i o n s i n 4 motor performance without any apparent temporal r e l a t i o n s h i p t o o r a l i n t a k e of levodopa (Klawns 1984). F o r the p a t i e n t s , the l o s s of response t o levodopa means more time spent i n a p a r k i n s o n i a n s t a t e ( " o f f " ) and l e s s i n an improved one ("on"). When these " o n - o f f " o s c i l l a t i o n s become u n p r e d i c t a b l e , s u b j e c t s can no l o n g e r p l a n d a i l y a c t i v i t i e s around drug a d m i n i s t r a t i o n and the impact on l i f e - s t y l e i s p r o f o u n d (Quinn 1987). These c o n c e p t s a r e w e l l i l l u s t r a t e d i n the f o l l o w i n g e x t r a c t from a l e t t e r w r i t t e n by a p a t i e n t w i t h the " o n - o f f " phenomenon (Lees 1989): ""On" i s q u i t e simply normal; I can s u r v i v e a d i n n e r p a r t y , d r i v e a c a r , w r i t e a f a i r , round hand, my v o i c e i s normal. I can f a i l a s l e e p r a t h e r e a s i l y u n l e s s I am t r y i n g not t o . " O f f " on the o t h e r hand i s v e r y u n p l e a s a n t . I l o s e almost a l l motor power i n my l e g s ; and t h i s p a r a l y s i s i n c r e a s i n g l y now spreads t o my arms. Sometimes odd p a i n s and cramps move round th e body. There i s no p o s i t i o n i n which I am c o m f o r t a b l e . I can't w r i t e . I c a n ' t t y p e , my speech i s s l u r r e d and low powered. The " o f f " comes on w i t h i n c r e a s i n g l y l i t t l e warning." The development of u n p r e d i c t a b l e motor o s c i l l a t i o n s i s u s u a l l y accompanied by the appearance of secondary e f f e c t s such as d y s k i n e s i a s (abnormal i n v o l u n t a r y movements) a t the time of maximum b e n e f i t from m e d i c a t i o n (Quinn 1987). A c c o r d i n g t o Quinn (1987), most p a t i e n t s p r e f e r e x p e r i e n c i n g i n v o l u n t a r y movements over a s t a t e of p a r k i n s o n i s m . However, f o r some p a t i e n t s w i t h s e v e r e "on" p e r i o d d y s k i n e s i a s , t h e "on" s t a t e can be almost as d i s a b l i n g as the " o f f " s t a t e (Quinn 1987). Random o s c i l l a t i o n s i n motor performances a r e c o n s i d e r e d t o be the most s e r i o u s problem e n c o u n t e r e d w i t h levodopa t h e r a p y , p r i m a r i l y 5 because t h e r e i s no u n i v e r s a l treatment f o r i t (Lees 1989). A f t e r about f i v e y e a r s of use, over 50% of p a t i e n t s e x p e r i e n c e u n s t a b l e c l i n i c a l r e s p o n s e s t o levodopa (Quinn 1984). The mechanism l e a d i n g t o the l o s s of c l i n i c a l e f f i c a c y of L-dopa over time i s thought t o be m a i n l y due t o a d e c r e a s e i n t h e c a p a c i t y of the b r a i n t o produce and s t o r e dopamine ( K u r l a n 1987). As a r e s u l t , d e c l i n e s i n t h e c i r c u l a t i n g c o n c e n t r a t i o n s of levodopa a r e no l o n g e r b u f f e r e d by the b r a i n and r e s u l t i n motor f l u c t u a t i o n s . Other f a c t o r s such as changes i n the p e r i p h e r a l p h a r m a c o k i n e t i c h a n d l i n g of levodopa are s uggested t o p l a y a r o l e i n the development of the " o n - o f f " phenomenon (Quinn 1989). THE EFFECT OF DIETARY PROTEIN ON THE EFFICACY OF L-DOPA A d m i n i s t r a t i o n of l o w - p r o t e i n d i e t s t o p a t i e n t s w i t h u n p r e d i c t a b l e motor f l u c t u a t i o n s has c o n s i s t e n t l y been shown t o improve motor performance and i n c r e a s e t o t a l p e r c e n t a g e of time "on", when compared w i t h h i g h or r e g u l a r p r o t e i n d i e t s ( P i n c u s and B a r r y 1987abc, 1988, T s u i a t a l . 1989). T h i s phenomenon appears t o r e s u l t m a i n l y from a d e c r e a s e i n the plasma c o n c e n t r a t i o n of d i e t a r y - d e r i v e d LNAAs t h a t compete w i t h levodopa f o r t r a n s p o r t i n t o the b r a i n ( D a n i e l e t a l . 1975, Nutt e t a l . 1984). In a s e r i e s of s h o r t - t e r m h o s p i t a l - b a s e d s t u d i e s , P i n c u s and B a r r y (1987abc, 1988) compared the e f f e c t of v e r y low daytime p r o t e i n i n t a k e (7g) w i t h the e f f e c t of h i g h e r p r o t e i n i n t a k e (65g or 160g) on the motor 6 performance of groups of p a t i e n t s s u f f e r i n g from u n p r e d i c t a b l e response f l u c t u a t i o n s t o levodopa. The levodopa dose f o r each p a t i e n t was co n s t a n t d u r i n g the p e r i o d of study. In each t r i a l , over 80% of the s u b j e c t s p erformed s i g n i f i c a n t l y b e t t e r when consuming low amounts of p r o t e i n t h a n h i g h amounts, as measured by a " b l i n d " p h y s i c i a n u s i n g a s t a n d a r d i z e d d i s a b i l i t y s c a l e . P i n c u s and B a r r y (1987c) r e p o r t e d t h a t i n the c o u r s e of a day, plasma LNAA c o n c e n t r a t i o n s appeared t o be i n v e r s e l y r e l a t e d t o the c l i n i c a l performance of p a t i e n t s . When plasma LNAA l e v e l s were h i g h , the p a t i e n t s were " o f f " ; when t h e s e l e v e l s were r e l a t i v e l y low, the p a t i e n t s were "on". More r e c e n t l y , t e n p a r k i n s o n i a n p a t i e n t s e x p e r i e n c i n g u n p r e d i c t a b l e response f l u c t u a t i o n s t o levodopa p a r t i c i p a t e d i n a d o u b l e - b l i n d c r o s s - o v e r s t u d y ( T s u i et a l . 1989). The s u b j e c t s r e c e i v e d two d i f f e r e n t p r o t e i n - c o n t a i n i n g d i e t s , which l o o k e d and t a s t e d a l i k e . Each d i e t was consumed f o r f i v e c o n s e c u t i v e days, w i t h a two day r e s t p e r i o d i n between. The h i g h p r o t e i n d i e t p r o v i d e d 70g p r o t e i n f o r women and 80g p r o t e i n f o r men, e q u a l l y d i s t r i b u t e d throughout each day. The low p r o t e i n d i e t c o n t a i n e d 40 and 50g p r o t e i n / d a y f o r men and women r e s p e c t i v e l y , w i t h minimal p r o t e i n i n t a k e d u r i n g daytime ( l e s s t h a n 7g) and the r e s t a f t e r 5:00 PM. Three times d a i l y , the s u b j e c t s were r a t e d by a " b l i n d " p h y s i c i a n f o r t h e i r motor performance, a c c o r d i n g t o a s t a n d a r d i z e d d i s a b i l i t y s c a l e . The p a r t i c i p a n t s kept h o u r l y r e c o r d s of t h e i r motor f l u c t u a t i o n s u s i n g an " o n - o f f " c h a r t . The r e s u l t s i n d i c a t e d t h a t seven out of t e n s u b j e c t s e x p e r i e n c e d a s i g n i f i c a n t improvement i n 7 motor performance and s i g n i f i c a n t l y fewer " o f f " p e r i o d s w h i l e on the low p r o t e i n d i e t . S u b j e c t i v e l y , s i x p a t i e n t s n o t e d improvement w h i l e on the low p r o t e i n d i e t . The r e s u l t s from t h e s e c o n t r o l l e d i n p a t i e n t s t u d i e s appear t o demonstrate t h a t r e s t r i c t i o n of d i e t a r y p r o t e i n i s a s u c c e s s f u l approach t o c o n t r o l motor f l u c t u a t i o n s . However, the q u e s t i o n as t o whether the r e s t r i c t e d p r o t e i n d i e t i s p r a c t i c a l l y a p p l i c a b l e t o f r e e - l i v i n g p a t i e n t s was not a d d r e s s e d . APPLICATION OF A RESTRICTED PROTEIN DIET TO FREE-LIVING INDIVIDUALS WITH PARKINSON' S DISEASE To d a t e , o n l y one study ( R i l e y and Lang 1988) has attempted t o i n v e s t i g a t e the e f f e c t of a r e s t r i c t e d p r o t e i n d i e t on an o u t p a t i e n t p o p u l a t i o n w i t h P a r k i n s o n ' s d i s e a s e . T h i r t y s u b j e c t s e x p e r i e n c i n g r e s p onse f l u c t u a t i o n s t o L-dopa were i n d i v i d u a l l y i n s t r u c t e d on how t o l i m i t daytime p r o t e i n i n t a k e t o a p p r o x i m a t e l y seven grams. Food i n t a k e was u n r e s t r i c t e d from d i n n e r u n t i l bedtime. The r a t i o n a l e of t h i s approach was t o enhance the p a t i e n t s ' s e n s i t i v i t y t o levodopa d u r i n g daytime, and t o use the l a s t p a r t of the day as a c a t c h - u p p e r i o d f o r i n t a k e of p r o t e i n and o t h e r n u t r i e n t s . The s u b j e c t s were asked t o remain on the d i e t f o r a minimum of f o u r weeks and were r e q u i r e d t o keep a r e c o r d of t h e i r d a i l y "on" and " o f f " f l u c t u a t i o n s . The a u t h o r s r e p o r t e d t h a t w i t h i n a week, 17 of the 28 s u b j e c t s who completed the study e x p e r i e n c e d a s u b s t a n t i a l and s u s t a i n e d improvement 8 i n c l i n i c a l r esponse t o levodopa. T h i s was m a n i f e s t e d by a 50% r e d u c t i o n i n the number of hours spent i n the " o f f " s t a t e . However, no s t a t i s t i c a l a n a l y s i s was r e p o r t e d and t h u s , o n l y l i m i t e d c o n c l u s i o n s can be drawn from t h e s e r e s u l t s . The p o t e n t i a l impact of the r e s t r i c t e d p r o t e i n d i e t on n u t r i t i o n a l s t a t u s of p a t i e n t s was i n v e s t i g a t e d by measuring plasma albumin a t the b e g i n n i n g of the study and a f t e r f o u r weeks on the d i e t and by m o n i t o r i n g body weight changes. Because of i t s r e l a t i v e l y l o n g h a l f -l i f e and l a r g e body p o o l s i z e ( H a i d e r and H a i d e r 1984), plasma albumin may not have r e f l e c t e d s h o r t - t e r m changes i n p r o t e i n metabolism caused by a moderate r e d u c t i o n i n d i e t a r y p r o t e i n . The a u t h o r s d i d not p r o v i d e the serum albumin r e s u l t s . However, t h e y i n d i c a t e d t h a t weight l o s s a veraged 0.32 kg over the f o u r week d i e t p e r i o d . The s t a t i s t i c a l s i g n i f i c a n c e of t h i s change was not r e p o r t e d . The p a r t i c i p a n t s ' g e n e r a l a c c e p t a n c e of the d i e t appeared t o be p o s i t i v e s i n c e the o v e r a l l drop out r a t e was low. N o n e t h e l e s s , the s u b j e c t s complained of a p e r s i s t e n t f e e l i n g of daytime hunger and about the p a l a t a b i l i t y of the d i e t . The f i n d i n g s from R i l e y and Lang's study seem t o i n d i c a t e t h a t the r e s t r i c t e d p r o t e i n d i e t c o u l d be s u c c e s s f u l l y used by f r e e - l i v i n g p a t i e n t s t o c o n t r o l motor f l u c t u a t i o n s . However, the p o t e n t i a l i m p l i c a t i o n s of the r e s t r i c t e d p r o t e i n d i e t on t h e n u t r i e n t i n t a k e s and n u t r i t i o n a l s t a t u s of p a t i e n t s have not y e t been i n v e s t i g a t e d . 9 ASSESSMENT OF PARKINSONIAN DISABILITY Methods t h a t have been d e v e l o p e d t o a s s e s s the s e v e r i t y of p a r k i n s o n i a n d i s a b i l i t y and the c l i n i c a l response t o t h e r a p y i n c l u d e : 1) D i s a b i l i t y s c a l e s , i n which s k i l l e d e v a l u a t o r s s u b j e c t i v e l y q u a n t i f y motor symptoms and/or p a t i e n t s ' a b i l i t y t o p e r f o r m a c t i v i t i e s of d a i l y l i v i n g ; 2) n e u r o p h y s i o l o g i c a l t e s t s t h a t o b j e c t i v e l y q u a n t i f y p a r t i c u l a r motor d i s t u r b a n c e s , e.g. t o r q u e motor t o measure r i g i d i t y a t the w r i s t ; and 3) " o n - o f f " c h a r t s , on which p a t i e n t s r a t e each hour of the day as "on" or " o f f " a c c o r d i n g t o t h e i r c l i n i c a l s t a t u s . A c c o r d i n g t o J a n k o v i c (1987): "The most u s e f u l i n d i c a t o r of c l i n i c a l d i s a b i l i t y i n a p a t i e n t w i t h l e v o d o p a - i n d u c e d c l i n i c a l f l u c t u a t i o n s , i s not n e c e s s a r i l y the degree of tremor, r i g i d i t y , b r a d y k i n e s i a or p o s t u r a l i n s t a b i l i t y observed i n the o f f i c e , but t h e p e r c e n t a g e of time " o f f " d u r i n g the t o t a l waking t i m e . " In the o p i n i o n of s e v e r a l a u t h o r s ( J a n k o v i c k 1982, Marsden e t a l . 1984), t h e p e r c e n t a g e of time "on" and " o f f " i s a l s o v e r y s i g n i f i c a n t from the p a t i e n t s ' p o i n t of view because of the marked d i f f e r e n c e i n f u n c t i o n a l c a p a c i t y between the two s t a t e s . The " o n - o f f " c h a r t method r e p r e s e n t s a s u b j e c t i v e measure of p a r k i n s o n i a n d i s a b i l i t y s i n c e p a t i e n t s i n t e r p r e t and r a t e t h e i r own c l i n i c a l c o n d i t i o n s . N e v e r t h e l e s s , i t i s the o n l y method t h a t can be p r a c t i c a l l y a p p l i e d i n an o u t p a t i e n t s e t t i n g . The s e l f - s c o r i n g c h a r t has been used by r e s e a r c h e r s as an e x c l u s i v e i n d i c a t o r of motor performance i n f r e e - l i v i n g P a r k i n s o n ' s d i s e a s e p a t i e n t s (Lees e t a l . 1977, R i l e y and Lang 1988). 10 ASSESSMENT OF DIETARY STATUS There are s e v e r a l methods used f o r c o l l e c t i n g f o o d consumption d a t a and i n p r a c t i c e none has been shown " t o be b e t t e r t h a n o t h e r s . A c c o r d i n g t o Young (1981), i n a r e p o r t t o the Committee on Food Consumption P a t t e r n s , the b e s t method i s one t h a t w i l l be s e l e c t e d and adapted t o meet the needs of the p a r t i c u l a r study t o be undertaken. The w r i t t e n f o o d i n t a k e r e c o r d method has been s u c c e s s f u l l y used t o a s s e s s energy and n u t r i e n t i n t a k e s i n groups of f r e e - l i v i n g o l d e r p eople ( C a i r d e t a l . 1975, C l a r k e e t a l . 1981, Scythes e t a l . 1989). In a l i t e r a t e p o p u l a t i o n of e l d e r l y , t h e f o o d i n t a k e r e c o r d method minimizes memory e r r o r s a s s o c i a t e d w i t h o t h e r e x t e n s i v e l y used m e t h o d o l o g i e s , such as the d i e t a r y h i s t o r y of u s u a l i n t a k e s and t h e one o r s e v e r a l days r e c a l l ( S c h l e n k e r 1984). However, as d i s c u s s e d by B l o c k (1982), the i n t e r n a l v a l i d i t y of the f o o d r e c o r d (whether the method a c c u r a t e l y r e f l e c t s what i t i s i n t e n d e d t o measure) may be compromised by r e c o r d i n g e r r o r s . D i r e c t v a l i d a t i o n of the f o o d r e c o r d method i n a f r e e - l i v i n g p o p u l a t i o n p r e s e n t s c o n s i d e r a b l e p r a c t i c a l d i f f i c u l t i e s s i n c e i t i m p l i e s somehow knowing the " t r u e " i n t a k e . The i n t e r n a l v a l i d i t y of the seven-day d i e t a r y r e c o r d was d i r e c t l y t e s t e d by G e r s o v i t z e t a l . (1978) among a group of n o n - i n s t i t u t i o n a l i z e d e l d e r l y who were p a r t i c i p a t i n g i n a congregate meal program. S i x t y -t h r e e s u b j e c t s (ages 65 y e a r s and over) were i n s t r u c t e d on how t o complete a seven day d i e t a r y r e c o r d . Weekday l u n c h meals were p r o v i d e d a t the c o n g r e g a t e meal s i t e i n a s e t t i n g which p e r m i t t e d the 11 i n v e s t i g a t o r s t o measure the amount of f o o d t h a t was consumed by the s u b j e c t s , w i t h o u t t h e i r knowledge. By comparing mean l u n c h time i n t a k e of energy and n i n e n u t r i e n t s r e p o r t e d by the seven day r e c o r d s w i t h a c t u a l o b s erved i n t a k e s , i t was shown t h a t the r e c o r d s tended t o s y s t e m a t i c a l l y u n d e r e s t i m a t e a c t u a l i n t a k e s a l t h o u g h the d i f f e r e n c e was s i g n i f i c a n t f o r energy and t h i a m i n o n l y . U s i n g r e g r e s s i o n a n a l y s i s , the i n v e s t i g a t o r s showed t h a t the a c c u r a c y of the r e c o r d s d e c l i n e d from the b e g i n n i n g t o the end of the r e c o r d i n g p e r i o d . Records f o r days one and two were c o n s i s t e n t w i t h o b s e r v e d i n t a k e s f o r a l l n u t r i e n t s but p r o t e i n . By days f i v e t hrough seven, e s t i m a t e s f o r o n l y t h r e e n u t r i e n t s out of t e n were v a l i d . These r e s u l t s suggest g e n e r a l agreement between dat a p r o v i d e d by a group of e l d e r l y p eople u s i n g the seven-day f o o d r e c o r d method and a c t u a l mean i n t a k e s , but emphasizes the g r a d u a l d e c l i n e i n t h e respondents' r e c o r d i n g a c c u r a c y w i t h time. H i g h l y m o t i v a t e d s u b j e c t s , however, might be more l i k e l y t o r e c o r d a c c u r a t e l y over extended p e r i o d s of time. The number of f o o d i n t a k e r e c o r d days r e q u i r e d t o o b t a i n an a c c u r a t e e s t i m a t e of " u s u a l " energy and n u t r i e n t i n t a k e s f o r groups of i n d i v i d u a l s was a d d r e s s e d i n a study by B a s i o t i et a l . (1987). T h e i r c a l c u l a t i o n s were based on 365 c o n s e c u t i v e f o o d i n t a k e r e c o r d s completed by 13 male and 16 female a d u l t s , aged 21 t o 49 y e a r s . A p r e c i s e e s t i m a t e of the group's u s u a l i n t a k e of energy and n u t r i e n t s was d e f i n e d by the i n v e s t i g a t o r s as an X-day average i n t a k e f a l l i n g w i t h i n 10% of 12 the y e a r l y average i n t a k e , 95% of the time and was c a l c u l a t e d u s i n g the f o l l o w i n g f o r m u l a : D= ( Z ) 2 ( i n t e r i n d i v i d u a l S D ) 2 X 1  ( A ) ^ ( y e a r average i n t a k e ) ^ sample s i z e where D i s the number of days, Z i s the Z v a l u e d e r i v e d from s t a t i s t i c a l t a b l e s (1.96 a t the .05 l e v e l of s i g n i f i c a n c e ) ( S h a v e l s o n 1988) and A' i s the l e v e l of a c c u r a c y (10% or .1). The number of days of f o o d i n t a k e r e c o r d needed t o e s t i m a t e the groups' average i n t a k e s v a r i e d c o n s i d e r a b l y from n u t r i e n t t o n u t r i e n t , r a n g i n g from o n l y t h r e e days f o r energy t o as many as 30 t o 40 days f o r v i t a m i n s A and C. However, f o r most n u t r i e n t s , a p e r i o d of seven days was s u f f i c i e n t . Other s t u d i e s have a l s o shown wide v a r i a t i o n s i n i n t a k e of v i t a m i n s A and C and moderate v a r i a t i o n s i n energy i n t a k e w i t h i n d i f f e r e n t p o p u l a t i o n groups (Nelson e t a l . 1989). By examining the f o r m u l a i t can be seen t h a t i f s m a l l e r samples a r e used, a g r e a t e r number of days a r e r e q u i r e d t o e s t i m a t e the group's i n t a k e s a t the same l e v e l of s t a t i s t i c a l c o n f i d e n c e . However, i f the meal p a t t e r n i s more c o n s i s t e n t , i n t e r i n d i v i d u a l v a r i a b i l i t y i s reduced and s h o r t e r p e r i o d s a r e needed. T h i s s t u d y might have q u e s t i o n a b l e v a l i d i t y r e l a t e d t o the d u r a t i o n of the p e r i o d of r e c o r d k e e p i n g (1 y e a r ) , which i n t u r n might a f f e c t the p r e c i s i o n of the e s t i m a t e s . However, the r e s u l t s i n d i c a t e t h a t i n a sm a l l group of i n d i v i d u a l s , u s u a l i n t a k e of n u t r i e n t s t h a t show l a r g e i n t e r i n d i v i d u a l v a r i a b i l i t y cannot be a c c u r a t e l y e s t i m a t e d over a s h o r t p e r i o d of t i m e . In c o n c l u s i o n , k e e p i n g a w r i t t e n f o o d i n t a k e r e c o r d r e q u i r e s c o n s i d e r a b l e c o o p e r a t i o n from the s u b j e c t s , which p r o b a b l y l i m i t s i t s u s e f u l n e s s t o h i g h l y m o t i v a t e d i n d i v i d u a l s . A l t h o u g h problems of v a l i d i t y might a r i s e when the p e r i o d of r e c o r d k e e p i n g exceeds a few days, G e r s o v i t z e t a l . (1978) showed t h a t the d a t a o b t a i n e d from a group of e l d e r l y p e o p l e u s i n g t h e seven day f o o d r e c o r d method were g e n e r a l l y a c c u r a t e . F i n a l l y , l o n g e r p e r i o d s of time are r e q u i r e d t o a c c u r a t e l y e s t i m a t e u s u a l i n t a k e of n u t r i e n t s t h a t show l a r g e i n t e r i n d i v i d u a l v a r i a b i l i t y t h a n of those t h a t show s m a l l i n t e r i n d i v i d u a l v a r i a b i l i t y ( B a s i o t i s 1987). ASSESSMENT OF PROTEIN AND IRON STATUS Serum albumin and p r e a l b u m i n . Serum albumin and p r e a l b u m i n are commonly used t o a s s e s s the v i s c e r a l p r o t e i n s t a t u s of i n d i v i d u a l s and p o p u l a t i o n s . The assumption i s made t h a t a d e c r e a s e i n the serum c o n c e n t r a t i o n of t h ese p r o t e i n s i s a consequence of d e c r e a s e d l i v e r b i o s y n t h e s i s , which i s i n t u r n due t o a l i m i t e d s u p p l y of d i e t a r y energy and p r o t e i n and an a c t u a l d e c r e a s e i n organ mass (Tuten e t a l . 1985). Indeed, serum albumin has been shown t o c o r r e l a t e w i t h body c e l l mass (Forse 1980). Serum albumin has a h a l f - l i f e of about 20 days and a r e l a t i v e l y l a r g e body p o o l (60% of i t i s not i n c l u d e d i n the i n t r a v a s c u l a r compartment) and thus responds s l o w l y t o p r o t e i n and energy d e p r i v a t i o n ( H a i d e r and H a i d e r 1984). Serum prea l b u m i n has a s h o r t e r h a l f - l i f e (two t o t h r e e d a y s ) , q u i t e a s m a l l p o o l s i z e and has 14 been shown t o respond r a p i d l y t o n u t r i t i o n a l d e p l e t i o n ( C a r p e n t i e r e t a l . 1982) and r e p l e t i o n (Tuten e t a l . 1985). I t i s thus more s u i t a b l e t h a n serum albumin f o r a s s e s s i n g s h o r t - t e r m changes i n v i s c e r a l p r o t e i n s t a t u s . Hemoglobin and f e r r i t i n . A c c o r d i n g t o Cook (1976), the most d e s i r a b l e parameter of i r o n s t a t u s i n a p o p u l a t i o n i s a measurement of i r o n s t o r e s . In h e a l t h y a d u l t s , serum f e r r i t i n has been shown t o i n v e r s e l y c o r r e l a t e w i t h i r o n a b s o r p t i o n which i s c o n s i d e r e d as the most s e n s i t i v e i n d i r e c t measure of i r o n s t a t u s (Cook 1974). F e r r i t i n has a l s o been shown t o r e f l e c t m i l d i r o n d e f i c i e n c y s t a t e s (Jacobs 1982) t h a t o t h e r measurements (e.g. t o t a l i r o n b i n d i n g c a p a c i t y ) u s u a l l y f a i l t o d e t e c t ( B e u t l e r 1958). T h e r e f o r e , i t i s assumed t h a t changes i n serum f e r r i t i n l e v e l s i n normal s u b j e c t s r e f l e c t changes i n i r o n s t o r e s (Cook 1974). An a g e - r e l a t e d i n c r e a s e i n serum f e r r i t i n l e v e l s of 1-2 ng/ml/year has been observed (Cook 1974). To c o u n t e r a c t the e f f e c t of t h i s r i s e , P a t t e r s o n et a l . (1985) su g g e s t e d t h a t the c u t o f f r e f e r e n c e l e v e l f o r anemia be s h i f t e d upwards and showed t h a t serum f e r r i t i n remained a v a l u a b l e t o o l i n the assessment of i r o n s t a t u s i n o l d e r p e o p l e . Only when i r o n d e f i c i e n c y i s w e l l d e v e l o p e d w i l l hemoglobin p r o d u c t i o n be i m p a i r e d and b l o o d c o n c e n t r a t i o n s drop (Handbook of c l i n i c a l l a b o r a t o r y d a t a , 1968). The p r e v a l e n c e of below-normal hemoglobin v a l u e s i n c r e a s e s w i t h age and appears t o be i n d i c a t i v e of an 15 i n c r e a s e d p r e v a l e n c e of anemia ( T i m i r a s and Brownstein 1987). F o r t h i s r e a s o n , hemoglobin i s an important parameter t o measure i n the e l d e r l y . SUMMARY In c o n t r o l l e d environments, low daytime p r o t e i n d i e t s ( i . e . 7g b e f o r e 5PM) have been a s s o c i a t e d w i t h improvement of motor symptoms i n P a r k i n s o n ' s d i s e a s e p a t i e n t s e x p e r i e n c i n g u n p r e d i c t a b l e c l i n i c a l r esponse t o l e v o d o p a . Moreover, one study has suggested t h a t some f r e e -l i v i n g p a t i e n t s might a l s o b e n e f i t from daytime r e s t r i c t i o n of d i e t a r y p r o t e i n . P r i o r t o s u p p o r t i n g such a r e s t r i c t i v e d i e t as p a r t of the c l i n i c a l management of " o n - o f f " phenomenon, n u t r i t i o n a l and o t h e r p r a c t i c a l i m p l i c a t i o n s need t o be c o n s i d e r e d . 16 III. EXPERIMENTAL DESIGN AND METHODS SCREENING AND SELECTION OF SUBJECTS P o t e n t i a l s u b j e c t s were s e l e c t e d by s c r e e n i n g a l l c u r r e n t P a r k i n s o n ' s d i s e a s e p a t i e n t s ' m e d i c a l r e c o r d s (a t o t a l of a p p r o x i m a t e l y 300 c h a r t s ) a t the UBC Movement D i s o r d e r s C l i n i c , U n i v e r s i t y H o s p i t a l , UBC S i t e . S e l e c t i o n c r i t e r i a i n c l u d e d the f o l l o w i n g : Diagnosed as an u n p r e d i c t a b l e c l i n i c a l r e s p o n d e r t o Sinemet ( l e v o d o p a - c a r b i d o p a ) , not a l r e a d y f o l l o w i n g a severe t h e r a p e u t i c d i e t , not d y s p h a g i c and i n ot h e r w i s e good g e n e r a l h e a l t h . Recruitment l e t t e r s (appendix 1) were sent t o 30 r e s i d e n t s of g r e a t e r Vancouver, of whom 12 ( s i x men, s i x women) agre e d t o take p a r t i n the study. Each v o l u n t e e r , accompanied by a s u p p o r t e r (spouse or c a r e g i v e r ) when not l i v i n g a l o n e , was i n d i v i d u a l l y seen a t the U n i v e r s i t y H o s p i t a l , UBC S i t e p r i o r t o the b e g i n n i n g of the study. A v e r b a l d e s c r i p t i o n of the study was g i v e n a t t h a t time and w r i t t e n i n f o r m e d consent was o b t a i n e d (appendix 2 ) . A mini - m e n t a l s t a t e e x a m i n a t i o n was then performed (appendix 3 ) . F a i l u r e t o o b t a i n a normal s c o r e ( i . e . 24 out of 29) would have r e s u l t e d i n e x c l u s i o n from the study; however, none of the 12 s u b j e c t s f a i l e d the t e s t ( s c o r e range, 27 t o 29). Each p a r t i c i p a n t p r o v i d e d i n f o r m a t i o n r e g a r d i n g t h e i r a n t i p a r k i n s o n m e d i c a t i o n and d u r a t i o n of P a r k i n s o n ' s d i s e a s e . To ensure t h a t s u b j e c t s were on t h e most a p p r o p r i a t e drug regime, a c o n s u l t a t i o n a t the UBC Movement D i s o r d e r s C l i n i c was r e q u i r e d w i t h i n s i x months of b e g i n n i n g the stu d y . Appointments were made f o r t h o s e who d i d not meet t h i s r e q u i r e m e n t . L e t t e r s were sent t o each s u b j e c t ' s g e n e r a l p r a c t i t i o n e r (appendix 4) t o r e q u e s t t h a t t h e i r p a t i e n t ' s a n t i p a r k i n s o n m e d i c a t i o n remain u n a l t e r e d u n t i l t h e end of the study p e r i o d . PROTOCOL F i g u r e 1 p r e s e n t s a summary of the r e s e a r c h p r o t o c o l . The study was c a r r i e d out over a p e r i o d of e i g h t weeks d u r i n g May and June 1989. The s u b j e c t s remained on t h e i r normal d i e t d u r i n g the f i r s t two weeks and f o l l o w e d the r e s t r i c t e d p r o t e i n d i e t over the s u c c e e d i n g s i x weeks. P r i o r t o t h e b e g i n n i n g of the study, the 12 s u b j e c t s were a s s i g n e d t o one of f o u r groups. Each group of t h r e e s u b j e c t s and t h e i r s u p p o r t e r s (10 out of 12 s u b j e c t s were accompanied by a s u p p o r t e r ) was s c h e d u l e d t o a t t e n d f o u r meetings a t t h e U n i v e r s i t y H o s p i t a l d u r i n g t h e e n t i r e s t u d y p e r i o d . The groups met f o r up t o two hours on t h e f i r s t day of study weeks one, t h r e e and f i v e , and on the l a s t day of study week e i g h t . The r a t i o n a l e f o r c h o o s i n g the group meeting format (as opposed t o i n d i v i d u a l meetings) was t o p r o v i d e a s u p p o r t i v e environment i n which the p a r t i c i p a n t s c o u l d share problems and s o l u t i o n s w i t h each o t h e r . Each s u b j e c t completed a s e r i e s of t h r e e 6-day f o o d r e c o r d s of which one was completed w h i l e on t h e i r normal d i e t ( s t u d y week 2) and two were completed w h i l e on t h e r e s t r i c t e d p r o t e i n d i e t ( study weeks 4 18 < Usual diet >< Test diet-(WEEKS) -2 -1 Records 0 • Food intake • On/off 1st meeting • ins t r u c t i o n on use of forms 1 Records 2 • Food intake • On/off 2nd meeting • instruction on te s t diet • blood samples • ht/wt 3rd meeting • subjective evaluations • additional di e t i n s t r u c t i o n • wt 5 Records 6 Food intake On/off 4th meeting © subjective evaluations • blood samples • wt Figure 1 Experimental protocol and 8 r e s p e c t i v e l y ) . D u r i n g the same t h r e e 6-day p e r i o d s , the s u b j e c t s kept a r e c o r d of t h e i r d a i l y motor f l u c t u a t i o n s , u s i n g an " o n - o f f " c h a r t . The p a r t i c i p a n t s were i n s t r u c t e d on the use of the f o o d r e c o r d s and " o n - o f f " c h a r t s d u r i n g the f i r s t group meeting. The r e s t r i c t e d p r o t e i n d i e t was e x p l a i n e d d u r i n g the second group meeting. A f t e r the second and the s i x t h week on t h e r e s t r i c t e d p r o t e i n d i e t , t h e s u b j e c t s and t h e i r s u p p o r t e r s completed s u b j e c t i v e e v a l u a t i o n q u e s t i o n n a i r e s d e s i g n e d t o a s s e s s acceptance of the d i e t and t o i d e n t i f y s p e c i f i c problems encountered i n f o l l o w i n g the d i e t a t home. To determine the impact of the r e s t r i c t e d p r o t e i n d i e t on c e r t a i n a s p e c t s of the n u t r i t i o n a l s t a t u s , hemoglobin, serum albumin, p r e a l b u m i n and f e r r i t i n l e v e l s were d e t e r m i n e d a t the b e g i n n i n g and a t the end of the s i x week r e s t r i c t e d p r o t e i n d i e t p e r i o d . Body weight was m o n i t o r e d throughout the study. T h i s r e s e a r c h p r o j e c t was approved by the UBC C l i n i c a l S c r e e n i n g Committee f o r Research and Other S t u d i e s I n v o l v i n g Human S u b j e c t s (appendix 5 ) . 7- . THE DIETARY RECORD AND THE "ON-OFF" CHART D u r i n g the f i r s t group meeting, the p a r t i c i p a n t s were i n s t r u c t e d on how t o keep an a c c u r a t e 6-day f o o d r e c o r d (appendix 6 ) . They were asked t o r e c o r d a l l foods and beverages consumed, immediately a f t e r each meal or snack, i n ho u s e h o l d measures (by volume, dimension o r by 20 w e i g h t ) . Diagrams were p r o v i d e d t o h e l p the p a r t i c i p a n t s e s t i m a t e the dimension of c e r t a i n f r u i t s and v e g e t a b l e s (e.g. a medium a p p l e ) and the weight of v a r i o u s p o r t i o n s of meat and f i s h . The p a r t i c i p a n t s were asked t o i n c l u d e brand names, l a b e l i n f o r m a t i o n , methods of f o o d p r e p a r a t i o n and the time a t which each meal or snack was eat e n . I f v i t a m i n or m i n e r a l supplements were used, the brand name and daily-dosage taken had t o be r e c o r d e d . W r i t t e n i n s t r u c t i o n s and a sample meal's r e c o r d were g i v e n w i t h t h e f o o d d i a r i e s . The s u b j e c t s , a s s i s t e d by t h e i r s u p p o r t e r s ( i f a p p l i c a b l e ) were then asked t o r e c o r d t h e i r l a s t meal's f o o d and beverage i n t a k e s onto the s t a n d a r d forms. The r e c o r d s were r e v i e w e d w i t h t h e p a r t i c i p a n t s and i f needed, p r o c e d u r e s were c l a r i f i e d . D u r i n g the second h a l f of t h e meeting, the s u b j e c t s were i n s t r u c t e d on how t o keep a 6-day r e c o r d of t h e i r d a i l y motor f l u c t u a t i o n s , u s i n g an " o n - o f f " c h a r t (appendix 7 ) . They were r e q u i r e d t o r a t e each awake hour p e r i o d as "on" or " o f f " a c c o r d i n g t o t h e p r e v a i l i n g c l i n i c a l s t a t e e x p e r i e n c e d d u r i n g t h a t time i n t e r v a l ( >30 min.). The s u b j e c t s were "on" when t h e i r P a r k i n s o n ' s d i s e a s e symptoms were w e l l c o n t r o l l e d by the m e d i c a t i o n . They were " o f f " when e x p e r i e n c i n g some P a r k i n s o n ' s d i s e a s e symptoms, r e f l e c t i n g a l a c k of response t o the m e d i c a t i o n . Attempts were made t o c l a r i f y t h e d i f f e r e n c e s between d y s k i n e s i a (abnormal i n v o l u n t a r y movements) which i s a s i d e e f f e c t from levodopa and i s a s s o c i a t e d w i t h t h e "on" s t a t e and p a r k i n s o n i a n symptoms which are a s s o c i a t e d w i t h the " o f f " s t a t e . In an attempt t o q u a l i f y the s e v e r i t y of t h e i r " o f f " p e r i o d s , the s u b j e c t s were asked t o t r y t o d i s c r i m i n a t e between two d i f f e r e n t l e v e l s of symptom s e v e r i t y : L e v e l 1 when, d e s p i t e the pr e s e n c e of symptoms, they remained independent i n c a r r y i n g out d a i l y a c t i v i t i e s ; and l e v e l 2, when th e y r e q u i r e d a s s i s t a n c e i n c a r r y i n g out d a i l y a c t i v i t i e s . However, s i n c e most s u b j e c t s d i d not c o n s i s t e n t l y complete t h i s s e c t i o n of the c h a r t , t h e s e d a t a were not a n a l y z e d . F i n a l l y , the " o n - o f f " c h a r t i n c l u d e d a s e c t i o n i n which the s u b j e c t s had t o r e c o r d each Sinemet dose, p r i m a r i l y t o h e l p i n c r e a s e compliance t o the m e d i c a t i o n regimen. The s u b j e c t s were asked t o complete the f o o d r e c o r d and the "on-o f f " c h a r t f o r s e v e r a l days i n the week f o l l o w i n g the f i r s t meeting u n t i l t h e y f e l t c o n f i d e n t of t h e i r a b i l i t y t o complete them a c c u r a t e l y . These d a t a were not r e t a i n e d f o r a n a l y s i s . P a r t i c i p a n t s e n c o u n t e r i n g any problems i n the use of t h e r e c o r d i n g forms were a b l e t o c o n t a c t the i n v e s t i g a t o r over the phone a t any t i m e . Each s u b j e c t was c a l l e d on the day p r e c e d i n g the b e g i n n i n g of each r e c o r d i n g p e r i o d , t o r e v i e w b r i e f l y the r e c o r d i n g p r o c e d u r e s , and t o remind him or her t o keep r e c o r d s f o r t h e f o l l o w i n g 6-day p e r i o d . The t h r e e r e m a i n i n g meetings were h e l d on the days i m m e d i a t e l y f o l l o w i n g c o m p l e t i o n of each 6-day r e c o r d i n g p e r i o d . Completed f o o d d i a r i e s and " o n - o f f " c h a r t s were c o l l e c t e d and reviewed w i t h each s u b j e c t t o c l a r i f y any ambiguous e n t r i e s . As r e q u i r e d , new f o o d d i a r i e s and " o n - o f f " c h a r t s were p r o v i d e d f o r t h e next r e c o r d i n g p e r i o d . 22 THE RESTRICTED PROTEIN DIET The r e s t r i c t e d p r o t e i n d i e t was e x p l a i n e d t o t h e p a r t i c i p a n t s d u r i n g t h e second group meeting. The d i e t was d e s i g n e d t o l i m i t p r o t e i n i n t a k e p r i o r t o the evening meal t o about lOg, d i s t r i b u t e d between two meals and two snacks (appendix 8 ) . Daytime f o o d i n t a k e c o n s i s t e d of a maximum of t h r e e s e r v i n g s of bread or c e r e a l / a maximum of t h r e e s e r v i n g s of f r u i t and u n l i m i t e d amounts of c e r t a i n v e r y low p r o t e i n v e g e t a b l e s (e.g. l e t t u c e , cucumber), f a t s and o i l s , sugar, condiments and n o n - d a i r y creamer. Commercially p r e p a r e d low p r o t e i n p r o d u c t s such as bread, p a s t a and c o o k i e s made w i t h s t a r c h s u b s t i t u t e d f o r f l o u r were a l s o p e r m i t t e d i n u n l i m i t e d q u a n t i t i e s . However, because of t h e i r l i m i t e d a v a i l a b i l i t y and h i g h c o s t , t h e i r use was o p t i o n a l . D u r i n g the meeting t h e p a r t i c i p a n t s were i n v i t e d t o t a s t e samples of c e r t a i n of t h e s e low p r o t e i n p r o d u c t s . Food i n t a k e was u n r e s t r i c t e d from d i n n e r u n t i l bedtime and the s u b j e c t s were encouraged t o consume n u t r i e n t - d e n s e f o o d s , p a r t i c u l a r l y h i g h - p r o t e i n foods such as meat and d a i r y p r o d u c t s d u r i n g t h i s l a s t p a r t of the day. D i e t i n s t r u c t i o n m a t e r i a l i n c l u d i n g menu i d e a s was g i v e n t o each p a r t i c i p a n t (appendix 8 ) . The s u b j e c t s and t h e i r s u p p o r t e r s were then asked t o p l a n a daytime menu sample i n acc o r d a n c e w i t h the g u i d e l i n e s and the s u b j e c t s ' own t a s t e s . The menu samples were reviewed and d i s c u s s e d w i t h the p a r t i c i p a n t s . 23 ANTHROPOMETRIC MEASUREMENTS A l l s u b j e c t s were weighed, wearing l i g h t i n d o o r c l o t h i n g and wi t h o u t shoes on a H e a l t h 0 Meter s t a n d a r d i z e d s c a l e ( C o n t i n e n t a l S c a l e C o r p o r a t i o n , B r i d g e v i e w , I l l i n o i s , USA). Weights were o b t a i n e d d u r i n g the second, t h i r d and f o u r t h group meetings. H e i g h t w i t h o u t shoes was measured once d u r i n g t h e study, u s i n g a c a l i b r a t e d r o d . The Body Mass Index (body weight i n kg d i v i d e d by the square of t h e h e i g h t i n meters) was c a l c u l a t e d f o r each s u b j e c t . BIOCHEMICAL ANALYSES A b l o o d sample was o b t a i n e d by v e n i p u n c t u r e from each s u b j e c t , a t a p p r o x i m a t e l y t h e same time of day (12:00 PM), b e f o r e and a f t e r the s i x week r e s t r i c t e d p r o t e i n d i e t p e r i o d . B l o o d samples were drawn and a n a l y z e d f o r hemoglobin, serum f e r r i t i n and serum albumin a t the Department of L a b o r a t o r y M e d i c i n e , U n i v e r s i t y H o s p i t a l , UBC S i t e and a n a l y z e d f o r serum p r e a l b u m i n a t the Department of C l i n i c a l C h e m i s t r y , Vancouver G e n e r a l H o s p i t a l . Methods f o r the d e t e r m i n a t i o n s were: Hemoglobin, cyanomethemoglobin (COULTER STKR)(Mitruka and Rawnsley, 1981); albumin, b r o m c r e s o l green dye (KODAK EKTACHEM)(Savory and Hammond 1980); p r e a l b u m i n , r a d i a l i m m u n o d i f f u s i o n p l a t e s f o r q u a n t i t a t i v e p r e a l b u m i n (BEHRING)(Goldsmith and Munson 1987); and f e r r i t i n , Radio Immuno Assay (BIO-RAD)(Bauer 1980). 24 QUESTIONNAIRES A f t e r c o m p l e t i o n of two and s i x weeks on the r e s t r i c t e d p r o t e i n d i e t , d u r i n g meetings t h r e e and f o u r r e s p e c t i v e l y , s u b j e c t s and s u p p o r t e r s each answered a s u b j e c t i v e e v a l u a t i o n q u e s t i o n n a i r e (appendices 9 and 10). M u l t i p l e c h o i c e q u e s t i o n s were used t o seek i n f o r m a t i o n about both s u b j e c t s ' and s u p p o r t e r s ' p e r c e p t i o n s r e l a t i v e t o the impact of the r e s t r i c t e d p r o t e i n d i e t on the s u b j e c t s ' m o b i l i t y ; t h e s u b j e c t s ' a c c e p t a n c e of the d i e t ; and t h e u s e f u l n e s s of s p e c i a l low p r o t e i n p r o d u c t s . The items l i s t e d ( e.g. daytime m o b i l i t y ) were r a t e d on a 5 p o i n t s c a l e as p e r c e i v e d b e i n g worse (-2,-1), the same (0) o r b e t t e r (1,2) on the r e s t r i c t e d p r o t e i n d i e t than on a r e g u l a r d i e t . Other q u e s t i o n s r e q u i r e d a "yes" or "no" re s p o n s e . Open-ended q u e s t i o n s were a l s o i n c l u d e d t o c o l l e c t p e r s o n a l comments from the p a r t i c i p a n t s . DATA TRANSFORMATION AND STATISTICAL ANALYSES Dietary records D i e t a r y r e c o r d s were coded by f o o d item and amount and a n a l y z e d f o r energy and the f o l l o w i n g n u t r i e n t s : p r o t e i n , l i p i d , c a r b o h y d r a t e s , c a l c i u m , i r o n , p otassium, magnesium, phosphorus, t h i a m i n , r i b o f l a v i n , n i a c i n , f o l a c i n , v i t a m i n s A, C, B6, B12, p a n t o t h e n a t e , u s i n g t h e Nutricom program (Smart E n g i n e e r i n g L t d . , North Vancouver, B.C.), c o n t a i n i n g Canadian n u t r i e n t f i l e d a t a . The database was complete f o r a l l n u t r i e n t s a n a l y z e d except magnesium, p a n t o t h e n a t e and v i t a m i n B6, 25 f o r which t h e r e were m i s s i n g v a l u e s f o r some f o o d s . N u t r i e n t supplement i n t a k e s were not i n c l u d e d i n the a n a l y s i s of the d i e t a r y d a t a . Mean d a i l y n u t r i e n t i n t a k e s d u r i n g the two d i e t p e r i o d s ( i . e . r e g u l a r and p r o t e i n r e s t r i c t e d ) were compared w i t h the 1983 RNIs (Recommended N u t r i e n t I n t a k e s f o r C a n a d i a n s ) ( H e a l t h and W e l f a r e Canada) f o r 50-74 y e a r o l d men and women. To i n v e s t i g a t e the changes i n d i e t c o m p o s i t i o n , mean i n d i v i d u a l 6-day n u t r i e n t i n t a k e s were a n a l y z e d w i t h an a n a l y s i s of v a r i a n c e (ANOVA) f o r a 2 (sex) x 3 ( r e c o r d i n g p e r i o d ) f a c t o r i a l experiment w i t h r e p e a t e d measures (RM) on the second f a c t o r . A l l RM ANOVA performed i n t h i s s tudy met the assumption of s p h e r i c i t y , as det e r m i n e d by the v a l u e of the e p s i l o n parameter (e>.8)(Schutz and G e s s a r o l i , 1987). When a p p l i c a b l e , p o s t - h o c c o n t r a s t s were performed t o determine s t a t i s t i c a l d i f f e r e n c e s between p a i r s of means. The B o n f e r r o n i p r o c e d u r e was used t o m a i n t a i n t h e o v e r a l l comparison e r r o r r a t e a t <.05. A t - t e s t was used t o i n v e s t i g a t e the d i f f e r e n c e i n daytime p r o t e i n i n t a k e p e r kg body weight between the s u b j e c t s who showed a s i g n i f i c a n t i n c r e a s e i n p e r c e n t time "on" and t h o s e who d i d n o t , w h i l e on the r e s t r i c t e d p r o t e i n d i e t . A l l s t a t i s t i c a l a n a l y s e s were a c c o m p l i s h e d w i t h SYSTAT, system f o r s t a t i s t i c s on the PC, second e d i t i o n (1989). 26 "On-off" c h a r t s F o r each s u b j e c t , the d a i l y number of "on" and " o f f " hours were counted. Most s u b j e c t s d i d not r e c o r d from one t o a maximum of t h r e e hours/day, once or t w i c e i n each s e t of 6-day " o n - o f f " c h a r t s . The d a i l y p e r c e n t a g e of "on" hours was c a l c u l a t e d as f o l l o w s : P e r c e n t time "on" = "on" hours x 100 " o f f " hours + "on" hours To i n v e s t i g a t e i n d i v i d u a l changes i n p e r c e n t time "on" over the t h r e e r e c o r d i n g p e r i o d s , a one way ANOVA on d a i l y p e r c e n t a g e "on" hours was e x e c u t e d . Data were A r c s i n e t r a n s f o r m e d t o improve n o r m a l i t y and homogeneity of v a r i a n c e . The Tukey HSD ( h o n e s t l y s i g n i f i c a n t d i f f e r e n c e ) t e s t was used as a m u l t i p l e comparison t e s t . To i n v e s t i g a t e the group's o v e r a l l change i n mean d a i l y p e r c e n t a g e "on" hours, a one way ANOVA w i t h RM was execu t e d . Post-hoc c o n t r a s t s were performed and the B o n f e r r o n i method was used t o m a i n t a i n the o v e r a l l comparison e r r o r r a t e a t <-05. -Biochemical parameters Hemoglobin, serum f e r r i t i n , albumin and p r e a l b u m i n d a t a were a n a l y z e d w i t h an ANOVA f o r a 2 (sex) x 2 (time p e r i o d ) f a c t o r i a l experiment w i t h RM on the second f a c t o r . 27 Body weight The weight d a t a were a n a l y z e d w i t h an ANOVA f o r a 2 (sex) x 3 (time p e r i o d ) f a c t o r i a l experiment w i t h RM on the second f a c t o r . Questionnaires F o r each q u e s t i o n , the number of answers per c a t e g o r y (worse/as u s u a l / b e t t e r or yes/no) was counted. The s u b j e c t s ' and s u p p o r t e r s ' comments were l i s t e d and grouped i n t o g e n e r a l c a t e g o r i e s . The d a t a g e n e r a t e d by the q u e s t i o n n a i r e s were found t o be i n a p p r o p r i a t e f o r s t a t i s t i c a l a n a l y s i s ; however, t h e y a r e r e p o r t e d i n the r e s u l t s s e c t i o n . The r e s p o n s e s t o some q u e s t i o n s were o m i t t e d e i t h e r because of a low r a t e of response or because of a m b i g u i t y . These q u e s t i o n s were: numbers two, f o u r , n i n e and e l e v e n A i n the s u b j e c t s ' q u e s t i o n n a i r e (appendix 9) and numbers two, seven and n i n e A i n the s u p p o r t e r s ' q u e s t i o n n a i r e (appendix 10) . LIMITATIONS OF THE STUDY A n a l y s i s of d a t a c o l l e c t e d a l l o w e d i n f e r e n c e s t o be made r e g a r d i n g : 1) t h e impact of the e x p e r i m e n t a l d i e t on energy and n u t r i e n t i n t a k e s , 2) t h e adequacy of the r e s t r i c t e d p r o t e i n d i e t r e l a t i v e t o the 1983 RNIs, 3) the e f f e c t of the e x p e r i m e n t a l d i e t on c e r t a i n a s p e c t s of the n u t r i t i o n a l s t a t u s and, 4) the impact of p r o t e i n r e s t r i c t i o n on the e f f i c a c y of l e v o d o p a . 28 L i m i t a t i o n s of t h i s s t u d y a r e : 1) The s u b j e c t s were not randomly s e l e c t e d from the r e g i o n a l p o p u l a t i o n of P a r k i n s o n ' s d i s e a s e p a t i e n t s s u f f e r i n g from u n p r e d i c t a b l e response f l u c t u a t i o n s t o l e v o d o p a . G i v e n the p a r t i c u l a r r e q u i r e m e n t s of th e study, the s u b j e c t sample was b i a s e d i n f a v o r of i n d i v i d u a l s who were m e n t a l l y a l e r t , h i g h l y m o t i v a t e d and c o o p e r a t i v e ; 2) The p r e e x p e r i m e n t a l d e s i g n used i n t h i s study a l l o w e d some i n f e r e n c e s t o be drawn about the impact of p r o t e i n r e s t r i c t i o n on the e f f i c a c y of levodopa t h e r a p y . The use of a d o u b l e - b l i n d e x p e r i m e n t a l d e s i g n would have a l l o w e d s t r o n g e r c a u s a l i n f e r e n c e s t o be made r e g a r d i n g the e f f e c t of p r o t e i n r e s t r i c t i o n on the t h e r a p e u t i c e f f i c a c y of l e v o d o p a . However, because s e v e r a l s t u d i e s had a l r e a d y p r o v i d e d e v i d e n c e t o support t h i s r e l a t i o n s h i p , i t was d e c i d e d t h a t the major f o c u s of t h i s o u t p a t i e n t study s h o u l d be the i n v e s t i g a t i o n of the p o t e n t i a l n u t r i t i o n a l i m p l i c a t i o n s of the r e s t r i c t e d p r o t e i n d i e t . Moreover, a d o u b l e - b l i n d d e s i g n would have i n v o l v e d p r e p a r a t i o n and consumption of s y n t h e t i c d i e t s , which would have i n t e r f e r e d w i t h the p r i m a r y o b j e c t i v e s of t h i s r e s e a r c h p r o j e c t . 29 IV. RESULTS SUBJECTS' CHARACTERISTICS E l e v e n of the twelve s u b j e c t s completed the study. One woman dropped out a f t e r study week f o u r because she was unable t o comply w i t h t h e d i e t . Her dat a were not i n c l u d e d i n the a n a l y s e s . T a b l e I d i s p l a y s a summary of t h e s u b j e c t s ' c h a r a c t e r i s t i c s . The ages of the men ranged from 55 t o 69 w i t h a mean of 62 y e a r s . The women's ages ranged from 65 t o 76 w i t h a mean of 72 y e a r s . The Body Mass Indexes ranged from 17.6 t o 26.7 w i t h a m a j o r i t y of the p a r t i c i p a n t s w i t h i n the d e s i r a b l e range of 20 t o 24.9. The mean d u r a t i o n of P a r k i n s o n ' s d i s e a s e was 13.7 y e a r s (range, 7 t o 22). A l l s u b j e c t s were t a k i n g l e v o d o p a - c a r b i d o p a (Sinemet). E i g h t s u b j e c t s were a l s o t a k i n g o t h e r a n t i p a r k i n s o n m e d i c a t i o n . E i g h t s u b j e c t s ( t h r e e women, f i v e men) were m a r r i e d and l i v e d w i t h t h e i r spouse whereas t h r e e were s i n g l e . One woman r e s i d e d i n a n u r s i n g home but a l l o t h e r s l i v e d i n t h e i r own home. Among t h i s group of p a t i e n t s , f o u r ( t h r e e men, one woman) s t a t e d t h a t t h e y had been t r y i n g t o reduce t h e i r p r o t e i n consumption f o r a few months p r i o r t o the b e g i n n i n g of t h e study. However, t h e i r p r o t e i n i n t a k e w h i l e on t h e i r u s u a l d i e t s was s i m i l a r t o t h o s e of the o t h e r s u b j e c t s . 30 Table I. Age, anthropometric data and medical c h a r a c t e r i s t i c s of the 11 subjects Subject Number Age Height Weight BMI Duration of Disease Medication P r o f i l e * (yrs) (cm) (kg) (kg/m*) (yrs) Males 1 59 175.0 67.1 21.9 9 S+A 2 69 165.0 59.2 21.7 17 S+A 3 69 165.5 72.8 26.7 22 S+B+A 4 65 181.0 81.7 24.9 17 S+B 5 55 170.0 75.5 26.1 7 S+B 6 56 165. 0 70.0 25.7 13 S+B+Ar Mean 62 170.2 71.0 24.5 14 (SD) 6 6.6 7.7 2 . 2 6 Females 1 75 155.5 42.9 17.6 9 S+B 2 76 162.0 54.8 20.9 16 S 3 71 166. 0 55.3 20.1 10 S+B+A 4 65 155.0 64.2 26.7 16 S+B 5 71 155.0 52.8 22 . 0 15 S+B Mean 72 158.7 54.1 21.5 13 (SD) 4 5.0 7.6 3 . 3 3 * Parkinson's disease medication only S=Sinemet, B=Bromocriptine, A=Amantadine, Ar=Artane 31 ADEQUACY OF THE SUBJECTS' NUTRIENT INTAKES RELATIVE TO THE RNIS T a b l e I I p r e s e n t s the mean i n t a k e of energy and n u t r i e n t s on r e g u l a r and e x p e r i m e n t a l d i e t s , i n a b s o l u t e and p e r c e n t RNI v a l u e s . On the r e g u l a r d i e t , the mean i n t a k e of energy and most n u t r i e n t s exceeded the RNIs f o r males and fe m a l e s . C a l c i u m i n t a k e i n females and pa n t o t h e n a t e i n t a k e i n both males and females were s l i g h t l y below t h e RNIs. On the r e s t r i c t e d p r o t e i n d i e t , o n l y c a l c i u m , magnesium and pa n t o t h e n a t e i n t a k e s were below the RNIs. C a l c i u m i n t a k e i n females was the o n l y n u t r i e n t s u b s t a n t i a l l y below the RNI. While i n t a k e of magnesium and pan t o t h e n a t e were a l s o below the RNIs, t h e n u t r i e n t a n a l y s i s program data bank was in c o m p l e t e w i t h r e s p e c t t o these two n u t r i e n t s and i n t a k e s a r e p r o b a b l y u n d e r e s t i m a t e d . N u t r i e n t supplement i n t a k e s were not i n c l u d e d i n the a n a l y s i s of the d i e t a r y d a t a . However, the s i x s u b j e c t s who d i d use supplements m a i n t a i n e d the same s u p p l e m e n t a t i o n regimen throughout t h e stu d y p e r i o d . CHANGES IN ENERGY AND NUTRIENT INTAKES The 2 (sex) x 3 ( r e c o r d i n g p e r i o d ) ANOVAs w i t h r e p e a t e d measures (RM) on the second f a c t o r i n d i c a t e d t h a t t h e r e was no sex x r e c o r d i n g p e r i o d i n t e r a c t i o n f o r energy and a l l n u t r i e n t s examined (p>.05), thus p e r m i t t i n g a simple i n t e r p r e t a t i o n of t h e two main e f f e c t s . 32 Table I I . Mean d a i l y intakes of energy and 15 nutrients of 11 subjects according to sex and d i e t Regular Diet Experimental Diet Energy and Intake Intake  Nutrients Sex Mean±SD %RNI MeanlSD %RNI Energy F 19751196 126 17591290 112 (Kcal) M 2351±413 107 24601611 112 Protein F 71±11 177 54113 135 (g) M 83±11 143 63113 109 Calcium F 716±110 90 4631159 58 (mg) M 857±238 107 6331229 79 Iron F 15±2 214 1212 171 (mg) M 17±3 212 1513 187 Potassium F 2765±442 170 22751356 140 (mg) M 3115±424 146 29011612 136 Vitamin A F 6522±3666 245 865912138 325 (IU) M 849815083 255 1036015331 311 Vitamin C F 121±59 269 109123 242 (mg) M 137125 228 141136 235 Thiamin F 1.4±0.1 175 1.210.1 150 (mg) M 1.910.5 190 1.710.4 170 Ri b o f l a v i n F 1.610.2 160 1.210.3 120 (mg) M 1.7+0.3 142 1.510.3 125 Niacin F 3116 207 2415 160 (NE) M 3815 211 30+6 167 Folacin F 187135 98 188146 99 (meg) M 237150 108 208124 95 Phosphorus F 12001139 150 8701243 109 (mg) M 14871247 186 11361194 142 Vitamin B12 F 3.311.0 165 3.114.8 155 (meg) M 2.910.7 145 4.214.5 210 Magnesium F 234149 127 151126 82 (mg) M 257145 107 198125 82 33 Table II cont'd Vitamin B6 2 F 1.6±0.3 145 1.1+0.1 137 (mg) M 2.0±0.6 167 1.6±0.6 168 Pantothenate 2 F 4.5±0.5 90 3.5±0.7 70 (mg) M 5.1±1.1 89 4.4±0.8 77 }• Average of recording periods 2 and 3 Intake of these nutrients may be underestimated 34 Averaged over sex, the r e s t r i c t e d p r o t e i n d i e t was a s s o c i a t e d w i t h a s i g n i f i c a n t d e c r e a s e i n daytime and t o t a l i n t a k e of p r o t e i n , t o t a l i n t a k e of c a l c i u m , i r o n , magnesium, phosphorus, n i a c i n , r i b o f l a v i n , v i t a m i n B6 and p a n t o t h e n a t e ( T a b l e I I I ) . The p o s t - h o c comparisons i n d i c a t e d t h a t daytime and t o t a l i n t a k e of p r o t e i n , t o t a l i n t a k e of c a l c i u m , i r o n , magnesium, phosphorus and n i a c i n dropped from r e c o r d i n g p e r i o d 1 ( r e g u l a r d i e t ) t o r e c o r d i n g p e r i o d 2 ( t e s t d i e t , f i r s t s e t ) and then p l a t e a u e d from r e c o r d i n g p e r i o d 2 t o 3 ( t e s t d i e t , second s e t ) ( T a b l e I I I ) . However, t h e B o n f e r r o n i m u l t i p l e comparison t e s t d i d not d e t e c t d i f f e r e n c e s between p a i r s of means f o r r i b o f l a v i n , p a n t o t h e n a t e and v i t a m i n B6. Intake of energy, c a r b o h y d r a t e s , l i p i d s , p o t a s s i u m , t h i a m i n , f o l a c i n and v i t a m i n s A, C and B12 d i d not change s i g n i f i c a n t l y over the t h r e e r e c o r d i n g p e r i o d s (Table I I I ) . Averaged over the r e c o r d i n g p e r i o d s , men had a s i g n i f i c a n t l y g r e a t e r i n t a k e of energy (F=5.07, p=.051), t h i a m i n (F=22.09, p=.001), p a n t o t h e n a t e (F=5.19 p=.049), i r o n (F=10.94, p=.009), phosphorus (F=5.12, p=.05) and magnesium (F=5.81, p=.039) than women. There was no o v e r a l l d i f f e r e n c e between sexes i n the i n t a k e of a l l o t h e r n u t r i e n t s . There was no s i g n i f i c a n t d i f f e r e n c e i n daytime p r o t e i n i n t a k e i n grams per kg body weight w h i l e on the r e s t r i c t e d p r o t e i n d i e t between the s u b j e c t s who showed a s i g n i f i c a n t i n c r e a s e i n p e r c e n t a g e "on" hours (mean ± SD, 0.198 ± 0.05g/kg), and those who d i d not (mean ± SD, 0.210 ± 0.05g/kg)(T=-1.16, p=.25). 35 Table I I I . Results of the repeated measure ANOVA on the changes i n nutrient intake over the three recording periods  Mean Intake 1 Energy and Recording Period' Recording Period Nutrient 1 2 3 Ef f e c t F(n) Energy 2180 2085 2198 N. S. (kcal) Protein Total 7 ? a 3 59 b 60 b 17.1 ( <.001) (g) Protein Day 36 a 12 b 13 b 62.3 ( <.001) (g) Carbohydrate 291 268 293 N. S. (g) L i p i d 81 89 90 N. S. (g) Calcium 793 a 572 b 539 b 17.6 | <.001) (mg) Iron 16 a 12 b 1 4 a b 5.2 | ' .016) (mg) Potassium 2956 2519 2713 N. S. (mg) Magnesium 247 a 167 b 186 b 20.0 ( '<•001) (mg) Phosphorus 1357 a 1016 b 1013 b 18.3 | '<• 001) (mg) Vitamin A 7600 10174 9090 N. S. (IU) Vitamin C 130 128 124 N. S. (mg) Niacin 35 a 27 b 28 b 11.6 ( . 001) (NE) Ri b o f l a v i n 1.6 1.3 1.3 4.0 [ .036) (mg) Thiamin 1.7 1.4 1.5 N. s. (mg) Folacin 214 200 198 N. s. (meg) Vitamin B6 1.8 1.3 1.5 5.3 ( .016) (mg) Vitamin B12 3.1 3.9 3.5 N. s. (meg) Pantothenate 4.8 3.9 3 . 5 4 . 5 [ .026) (mg) Intake data are averaged over sex 2 Recording period 1: Regular d i e t (Study Week 2) Recording period 2: Restricted protein d i e t (Study Week 4) Recording period 3: Restricted protein d i e t (Study Week 8) 3 Means with d i f f e r e n t l e t t e r s are s i g n i f i c a n t l y d i f f e r e n t ( o v e r a l l p<.05) 36 PERCENT TIME "ON" Three of the e l e v e n s u b j e c t s s i g n i f i c a n t l y i n c r e a s e d t h e i r p e r c e n t a g e of "on" hours w h i l e on the r e s t r i c t e d p r o t e i n d i e t ( T a b l e I V ) . There was no s i g n i f i c a n t change f o r the r e m a i n i n g e i g h t s u b j e c t s , a l t h o u g h s e v e r a l showed a t r e n d towards improvement. The r e p e a t e d measure ANOVA performed on the group d a t a i n d i c a t e d t h a t t h e r e was no s i g n i f i c a n t sex x r e c o r d i n g p e r i o d i n t e r a c t i o n (F=.5, p=.635). The o v e r a l l group improvement i n p e r c e n t time "on" was s t a t i s t i c a l l y s i g n i f i c a n t (F=19.1, p<.001). The p o s t - h o c c o n t r a s t s i n d i c a t e d t h a t the mean p e r c e n t a g e of "on" hours i n c r e a s e d s i g n i f i c a n t l y from r e c o r d i n g p e r i o d one (56% ± 21%) t o r e c o r d i n g p e r i o d two (64% ± 18%) and p l a t e a u e d from p e r i o d two t o t h r e e (66% + 18%). Averaged over the r e c o r d i n g p e r i o d s , t h e r e was no s i g n i f i c a n t d i f f e r e n c e between males' and females' p e r c e n t "on" hours (F=3.8, p=.082). BIOCHEMICAL ANALYSES The mean b l o o d c h e m i s t r y v a l u e s a c c o r d i n g t o sex and time a r e p r e s e n t e d i n T a b l e V. F o r a l l parameters measured, the sex x time i n t e r a c t i o n was not s i g n i f i c a n t (p>.05). Averaged over sex, t h e mean l e v e l s of hemoglobin, serum albumin and p r e a l b u m i n d i d not change over time (hemoglobin F=1.37, p=.272; albumin F=1.37, p=.272; pr e a l b u m i n F=2.08, p=.183). However, mean f e r r i t i n l e v e l s i n c r e a s e d s i g n i f i c a n t l y (F=11.90, p=.007). Averaged over time, the mean v a l u e s of hemoglobin, albumin and p r e a l b u m i n f o r men were h i g h e r than f o r women (hemoglobin 37 Table IV. Results from the one-way ANOVA on d a i l y percent "on" time Subj ect Mean ± SD % "On" He purs Recording Period Number Recording Periods L E f f e c t F(p) 1 2 3 Males 44±4 a 2 1 58±8 b 59±6 b 10.6 (.001) 2 ll±8 a 25±8 b 30±ll b 7.1 (.007) 3 56±20 65±5 63±13 N.S. 4 72±8 75±17 76±24 N.S. 5 39±22 45±11 51±12 N.S. 6 58±8 64±14 71±8 N.S. Females 1 54±16 71±14 67±5 N.S. 2 85±20 93±6 93±9 N.S. 3 53±8 58±11 52±8 N.S. 4 67±0 a 78±5 D 84±5 C 24.3 (<.001) 5 80±11 77±15 85±9 N.S. Recording Period 1: Regular Diet (Study Week 2) Recording Period 2: Restricted Protein Diet (Study Week 4) Recording Period 3: Restricted Protein Diet (Study Week 8) Means ± SD with d i f f e r e n t l e t t e r s are s i g n i f i c a n t l y d i f f e r e n t (<.05). 38 Table V. Biochemical parameters i n male and female subjects before and afte r the six week r e s t r i c t e d protein d i e t p e r i o d 1 Blood or plasma l e v e l 2 Parameter Sex Pre-diet Post-diet Normal range - 3 Hemoglobin F 125±8 126±8 120-160 (g/L) M 145±10 144±6 140-180 F e r r i t i n F 87±103 97±99 10-160 (mcg/L) M 120±75 138±79 18-250 Albumin F 39.4±1.5 38.6±2.9 35-50 (g/L) M 42.011.3 41.5±0.8 35-50 Prealbumin F 325±82 277±30 100-400 (mg/L) M 412±68 413±49 100-400 Averaged over sex, only f e r r i t i n showed a s i g n i f i c a n t change over time. Mean ± SD Data provided by the laboratories that performed the analyses 39 F=15.8, p=.003; albumin F=9.1, p=.015; p r e a l b u m i n F=11.5, p=.008). There was no s i g n i f i c a n t d i f f e r e n c e between sexes f o r f e r r i t i n l e v e l s . The mean v a l u e s of hemoglobin, f e r r i t i n and albumin of men and women and the mean v a l u e s of p r e a l b u m i n of women f e l l i n the a c c e p t a b l e range, a c c o r d i n g t o the l a b o r a t o r y s t a n d a r d s . The mean serum p r e a l b u m i n v a l u e s of men were s l i g h t l y above t h e normal upper l i m i t of 400 mg/L. BODY WEIGHT D u r i n g the s i x week p e r i o d of daytime p r o t e i n r e s t r i c t i o n , n i n e s u b j e c t s l o s t from .4 t o 2.9 kg body weight, one d i d not change, and one g a i n e d 1.7 kg. The 2 (sex) x 3(time p e r i o d ) ANOVA w i t h RM on the second f a c t o r i n d i c a t e d t h a t t h e r e was no s i g n i f i c a n t sex x time i n t e r a c t i o n (F=.8,p=.471). Averaged over sex, the o v e r a l l change i n body weight from 63.3 kg ( p r e - d i e t ) t o 62.6 kg t o 62.5 kg ( a f t e r 2 and 6 weeks on the r e s t r i c t e d p r o t e i n d i e t r e s p e c t i v e l y ) , was c l o s e t o b e i n g s i g n i f i c a n t (F=3.91, p=.054). I t appears t h a t the major l o s s e s i n body weight o c c u r r e d over t h e ' f i r s t two weeks on the r e s t r i c t e d p r o t e i n d i e t . SUBJECTIVE EVALUATIONS Subjects' perceptions R e s u l t s from the q u e s t i o n n a i r e s completed by t h e s u b j e c t s a r e summarized i n T a b l e VI, and a d d i t i o n a l comments a r e p r e s e n t e d i n T a b l e V I I . A f t e r two weeks on the r e s t r i c t e d p r o t e i n d i e t , s i x s u b j e c t s ( i n c l u d i n g the t h r e e s u b j e c t s w i t h a s i g n i f i c a n t i n c r e a s e i n p e r c e n t time "on") noted an improvement i n t h e i r daytime m o b i l i t y , two noted no change and t h r e e a worsening of t h e i r symptoms. A f t e r 6 weeks, t h i s r a t i o was 7 t o 2 t o 2. The s u b j e c t s i n t h e l a t t e r c a t e g o r y complained of more sudden and u n p r e d i c t a b l e f l u c t u a t i o n s . Comments from those who noted an improvement i n t h e i r m o b i l i t y i n c l u d e d the f o l l o w i n g : More independent i n c a r r y i n g out d a i l y a c t i v i t i e s , e.g. g e t t i n g d r e s s e d ; l e s s s e v e r e " o f f " p e r i o d s ; s l e e p i n g b e t t e r . A f t e r two weeks on the r e s t r i c t e d p r o t e i n d i e t , two s u b j e c t s out of e l e v e n f e l t t h a t t h e i r e v e n i n g symptoms were worse than w h i l e on t h e i r r e g u l a r d i e t . A f t e r 6 weeks, t h i s p r o p o r t i o n i n c r e a s e d t o f i v e out of e l e v e n . In g e n e r a l , the s u b j e c t s ' o p i n i o n s about the r e s t r i c t e d p r o t e i n d i e t seemed t o be c o n s i s t e n t from week two t o week s i x . A p p r o x i m a t e l y one t h i r d of them t r u l y d i s l i k e d the d i e t (4/11 i n q u e s t i o n n a i r e s 1 and 2 ) . Hunger p r i o r t o the e v e n i n g meal and the l a c k of v a r i e t y , p a r t i c u l a r l y a t l u n c h time, appeared t o be the major problems. The p r o p o r t i o n of s u b j e c t s who e n j o y e d the r e s t r i c t e d p r o t e i n d i e t i n c r e a s e d over time from 2/11 a t week two t o 5/11 a t week s i x , and more s u b j e c t s f e l t t h e i r g e n e r a l w e l l b e i n g was improved a f t e r s i x weeks (7/11) than a f t e r two weeks (2/ 9 ) . In both q u e s t i o n n a i r e s , about 50% of the s u b j e c t s (6/11) a f f i r m e d t h a t t h e y would f o l l o w the d i e t over an i n d e f i n i t e p e r i o d of time. 41 Table VI. Totals of multiple choice answers c o l l e c t e d from patients' questionnaires Quest. Number of Answers Ouestion Number1 Worse No Chancre Better Total Daytime Mobi l i t y 1 3 2 6 11 2 2 2 7 11 Evening Mobi l i t y 1 2 5 4 11 2 5 2 3 10 General well being 1 2 5 2 9 2 4 0 7 11 Enjoyment of d i e t 1 4 5 2 11 2 4 2 5 11 Hunger s a t i s f a c t i o n 1 7 2 1 10 p r i o r to dinner 2 6 2 2 10 Yes No Would you follow the 1 6 5 d i e t i n d e f i n i t e l y ? 2 6 5 Did you t r y spe c i a l 1 5 6 low-protein foods? 2 4 7 Are s p e c i a l low-protein 1 3 5 foods essential? 2 1 8 Questionnaire 1: After 2 weeks on r e s t r i c t e d protein d i e t 11 2: After 6 weeks on r e s t r i c t e d protein d i e t Table VII. Patients* comments Topic Quest. Number-1 Comments Positive Negative About mobility Sleep better(3)^ More independent in carrying out d a i l y a c t i v i t i e s (1) Sleep better(1) More independent in carrying out d a i l y a c t i v i t i e s (3) Less severe " o f f " periods (1) More sudden fluctuations(3) Evening symptoms seem worse(1) More sudden fluctuations(2) Evening symptoms seem worse(3) Daytime fatigue (1) D i f f i c u l t i e s with d i e t Food variety (4) Increasing food intake i n evening(1) Food variety (5) Eating out of home (1) About s p e c i a l low-protein foods - Too expensive (3) - Tasteless (4) 1 Questionnaire 1: After 2 weeks on r e s t r i c t e d protein d i e t " 2: After 6 weeks on r e s t r i c t e d protein d i e t 2 Numbers i n parentheses represent the number of s i m i l a r answers given 43 F i v e of the 11 p a r t i c i p a n t s t r i e d the s p e c i a l low p r o t e i n p r o d u c t s at home. However, a f t e r 6 weeks on the d i e t , o n l y one out of n i n e respondents b e l i e v e d t h a t t h e s e p r o d u c t s were an e s s e n t i a l p a r t of the r e s t r i c t e d p r o t e i n d i e t . The p a r t i c i p a n t s commented t h a t t h e s e s p e c i a l p r o d u c t s were t o o e x p e n s i v e and d i d not t a s t e good. Supporters' perceptions R e s u l t s from the q u e s t i o n n a i r e s completed by the n i n e s u p p o r t e r s a r e summarized i n T a b l e s V I I I and IX. In most c a s e s , the s u p p o r t e r s ' and the s u b j e c t s ' assessments of the impact of the r e s t r i c t e d p r o t e i n d i e t on the s u b j e c t s ' daytime and e v e n i n g m o b i l i t y were i n agreement, w i t h a s l i g h t tendency f o r the s u p p o r t e r s ' answers t o be more o p t i m i s t i c than the s u b j e c t s ' answers. A m a j o r i t y of s u p p o r t e r s (8/11 i n q u e s t i o n n a i r e 1 and 7/9 i n q u e s t i o n n a i r e 2) f e l t t h a t the s u b j e c t s ' daytime m o b i l i t y was improved w h i l e on the r e s t r i c t e d p r o t e i n d i e t . None of them noted a worsening of t h e s u b j e c t s ' m o b i l i t y . A f t e r the second week, o n l y two out of e i g h t s u p p o r t e r s f e l t t h a t the s u b j e c t s ' e v e n i n g symptoms were worse than w h i l e on t h e i r r e g u l a r d i e t . T h i s p r o p o r t i o n d e c r e a s e d t o one out of n i n e a f t e r s i x weeks. In both q u e s t i o n n a i r e s , s i x s u p p o r t e r s out of n i n e f e l t t h a t the p a t i e n t s were l e s s dependent on t h e i r c a r e d u r i n g daytime, w h i l e on the r e s t r i c t e d p r o t e i n d i e t . A f t e r week s i x , one s u p p o r t e r s t a t e d t h a t the p a t i e n t ' s dependency on h i s c a r e was worse. The s u p p o r t e r s ' comments i n r e g a r d s 44 Table VIII. Totals of multiple choice answers c o l l e c t e d from supporters' questionnaires Quest. Number of Answers  Question Number1 Worse No Change Better Total Daytime mobility 1 0 1 8 9 2 0 2 7 9 Evening mobility 1 2 2 4 8 2 1 3 5 9 Well being of 1 0 3 6 9 patient 2 1 2 6 9 Patient's dependency 1 0 3 6 9 on your care 2 1 2 6 9 Meal Planning 2 1 3 8 0 11 2 3 5 3 11 Time for meal 2 1 1 9 1 11 preparation 2 3 5 3 11 Yes No Would you encourage the patient to follow 1 7 0 the d i e t i n d e f i n i t e l y ? 2 6 2 Are s p e c i a l low-protein 1 2 5 foods essential? 2 1 6 Questionnaire 1: After 2 weeks on r e s t r i c t e d protein d i e t Questionnaire 2: After 6 weeks on r e s t r i c t e d protein d i e t This question was answered either by the supporter or the subject 45 Table IX. Supporters' comments Quest. Comments  Topic Number1 Positive Negative  About M o b i l i t y 1 - Patient i s more - Evening symptoms independent(2) 2 seem worse(2) - Patient sleeps better (1) - "Off" periods seem shorter 2 - Patient i s more - Evening symptoms independent(3) seem worse(2) - Patient sleeps better(2) - "Off" periods seem shorter(2) Problems with 1 - Hunger (2) d i e t - Food variety (3) - Increasing food intake xn evening(1) - Hunger (1) - Food variety (4) - Increasing food intake i n evening(2) Questionnaire 1: After 2 weeks on r e s t r i c t e d protein d i e t " 2: After 6 weeks on r e s t r i c t e d protein d i e t Numbers i n parentheses represent the number of s i m i l a r answers given 46 t o the s u b j e c t s ' changes i n m o b i l i t y were s i m i l a r t o the s u b j e c t s ' comments. A m a j o r i t y of s u p p o r t e r s i d e n t i f i e d hunger, as w e l l as the l a c k of v a r i e t y i n f o o d c h o i c e s p a r t i c u l a r l y a t l u n c h time, as b e i n g the important problems w i t h the r e s t r i c t e d p r o t e i n d i e t . A l s o , some ex p r e s s e d d i f f i c u l t y i n i n c r e a s i n g t h e p a t i e n t ' s f o o d i n t a k e i n the e v e n i n g . Q u e s t i o n s f i v e and s i x were answered e i t h e r by the s u b j e c t s or t h e i r s u p p o r t e r s , as a p p r o p r i a t e , f o r a t o t a l of e l e v e n answers. In a p r o p o r t i o n of a t l e a s t 8/11, i n both q u e s t i o n n a i r e s , the p a r t i c i p a n t s s t a t e d t h a t meal p l a n n i n g and the time i n v o l v e d i n meal p r e p a r a t i o n were no problem. A f t e r two and s i x weeks, s i x out of n i n e s u p p o r t e r s f e l t t h a t the s u b j e c t s ' g e n e r a l w e l l b e i n g was improved. A f t e r s i x weeks, s i x out of e i g h t s u p p o r t e r s s t a t e d t h a t they would encourage the s u b j e c t s t o c o n t i n u e f o l l o w i n g t h e r e s t r i c t e d p r o t e i n d i e t ( t h i s p r o p o r t i o n was 7/7 i n q u e s t i o n n a i r e 1 ) . In agreement with the s u b j e c t s ' o p i n i o n , most s u p p o r t e r s (5/7 i n q u e s t i o n n a i r e 1 and 6/7 i n q u e s t i o n n a i r e 2) d i d not b e l i e v e t h a t the s p e c i a l low p r o t e i n p r o d u c t s were an e s s e n t i a l p a r t of the r e s t r i c t e d p r o t e i n d i e t . 47 V. DISCUSSION In the p r e s e n t s t u d y e l e v e n f r e e - l i v i n g Parkins.on's d i s e a s e p a t i e n t s w i t h u n p r e d i c t a b l e motor-response f l u c t u a t i o n s t o levodopa f o l l o w e d a daytime r e s t r i c t e d p r o t e i n d i e t f o r s i x weeks. The p r i m a r y g o a l was t o a s s e s s the d i e t ' s impact on n u t r i e n t i n t a k e s and s e l e c t e d a s p e c t s of n u t r i t i o n a l s t a t u s . Major f i n d i n g s were t h a t 1) energy and n u t r i e n t i n t a k e s remained g e n e r a l l y adequate a c c o r d i n g t o 1983 RNIs, d e s p i t e s i g n i f i c a n t r e d u c t i o n s i n consumption of p r o t e i n and s e v e r a l o t h e r n u t r i e n t s , 2) impact on n u t r i t i o n a l s t a t u s , as measured by body weight and c e r t a i n i n d i c a t o r s of p r o t e i n and i r o n s t a t u s , was s m a l l and 3) some s u b j e c t s s i g n i f i c a n t l y i n c r e a s e d t h e i r "on" p e r i o d s w h i l e on the r e s t r i c t e d p r o t e i n d i e t . The f o l l o w i n g d i s c u s s i o n w i l l a d d r e s s the major f i n d i n g s of the s t u d y under the f o l l o w i n g c a t e g o r i e s : 1) Energy and n u t r i e n t i n t a k e s p r i o r t o and d u r i n g the r e s t r i c t e d p r o t e i n d i e t ; 2) impact of the r e s t r i c t e d p r o t e i n d i e t on body weight and p r o t e i n and i r o n s t a t u s ; 3) e f f e c t of t h e e x p e r i m e n t a l d i e t on p e r c e n t time "on"; and 4) comments on the a p p l i c a t i o n of the r e s t r i c t e d p r o t e i n d i e t t o f r e e - l i v i n g i n d i v i d u a l s . 48 ENERGY AND NUTRIENT INTAKES PRIOR TO AND DURING THE DAYTIME RESTRICTED PROTEIN DIET Regular diet The mean energy i n t a k e of both men and women p a r t i c i p a n t s was s l i g h t l y above the RNIs on t h e i r r e g u l a r d i e t s ( T a b l e I I ) . T h e i r r e s p e c t i v e average Body Mass Index f e l l i n the a c c e p t a b l e range of 20 t o 24.9, i n d i c a t i n g normal weight r e l a t i v e t o h e i g h t ( T a b l e I ) . Mean n u t r i e n t i n t a k e s were g e n e r a l l y s i m i l a r t o or i n excess of the RNIs, except f o r c a l c i u m i n females ( T a b l e I I ) . I t i s of note t h a t energy and n u t r i e n t i n t a k e s i n t h i s s e l e c t e d group of p a t i e n t s w i t h P a r k i n s o n ' s d i s e a s e appeared t o be much b e t t e r than i n the g e n e r a l e l d e r l y Canadian p o p u l a t i o n . Indeed, s t u d i e s on g e r i a t r i c n u t r i t i o n conducted i n Canada, i n c l u d i n g the N u t r i t i o n Canada N a t i o n a l Survey (1973), have c o n s i s t e n t l y shown t h a t energy consumption of o l d e r p e o p l e tends t o be below the RNI (Yeung and Imbach 1988, Scythes et a l . 1989). These s t u d i e s have a l s o shown t h a t t h e mean i n t a k e of s e v e r a l n u t r i e n t s i n c l u d i n g c a l c i u m , i r o n , t h i a m i n and v i t a m i n A and C i s commonly low i n t h e d i e t s of e l d e r l y C anadians, p a r t i c u l a r l y i n women. The a p p a r e n t l y h i g h e r energy and n u t r i e n t i n t a k e s of the sample group c o u l d be a t t r i b u t e d t o the s u b j e c t s ' o t h e r w i s e good g e n e r a l h e a l t h s t a t u s , s o c i o e c o n o m i c s t a t u s and t o the c a r e and support p r o v i d e d by spouses or c a r e g i v e r s . A c c o r d i n g t o B a s i o t i s e t a l . (1987), a g r e a t e r number of f o o d r e c o r d s than s i x p e r s u b j e c t would have been needed t o e s t i m a t e the group's annual average n u t r i e n t i n t a k e s w i t h a h i g h l e v e l of a c c u r a c y . Based on t h e i r f i n d i n g s and on f i n d i n g s of Nelson e t a l . (1989), the e s t i m a t e s of l o ng-term i n t a k e of v i t a m i n s A and C a r e the most l i k e l y t o be b i a s e d s i n c e i n t a k e of t h e s e n u t r i e n t s appear t o be w i d e l y v a r i a b l e between i n d i v i d u a l s i n w e l l d e f i n e d p o p u l a t i o n groups. D e s p i t e t h e s e l i m i t a t i o n s the n u t r i e n t d a t a p r e s e n t e d i n T a b l e I I suggest t h a t on average, the s u b j e c t s i n t h e p r e s e n t s t u d y consumed a more than adequate d i e t . Restricted protein diet The main o b j e c t i v e i n c o l l e c t i n g t h r e e 6-day f o o d r e c o r d s from each s u b j e c t was t o i n v e s t i g a t e the impact of the r e s t r i c t e d p r o t e i n d i e t on t h e group's u s u a l n u t r i e n t i n t a k e s . D i e t a r y r e c o r d e v a l u a t i o n s showed t h a t w h i l e on the r e s t r i c t e d p r o t e i n d i e t , s u b j e c t s d i d not a l t e r energy i n t a k e but s i g n i f i c a n t l y r e d u c e d consumption of s e v e r a l n u t r i e n t s i n c l u d i n g p r o t e i n , c a l c i u m , i r o n , magnesium, phosphorus and n i a c i n ( T a b l e I I I ) . The a n a l y s i s of v a r i a n c e a l s o d e t e c t e d a s i g n i f i c a n t r e d u c t i o n i n consumption of r i b o f l a v i n , v i t a m i n B6 and p a n t o t h e n a t e , a l t h o u g h t h e B o n f e r r o n i a p o s t e r i o r i t e s t , which i s c o n s e r v a t i v e ( W i l k i n s o n 1989), f a i l e d t o d e t e c t d i f f e r e n c e s among r e c o r d i n g p e r i o d i n t a k e s . The agreement between mean v a l u e s o b t a i n e d d u r i n g r e c o r d i n g p e r i o d s two and t h r e e ( T a b l e I I I ) s u g g e s t s t h a t the 6-day f o o d r e c o r d method p r o v i d e d a r e l i a b l e r e f l e c t i o n of the changes i n n u t r i e n t i n t a k e s i n d u c e d by the r e s t r i c t e d p r o t e i n d i e t . However, a l o n g e r p e r i o d of 50 time might have been needed t o e s t i m a t e a c c u r a t e l y the impact of the e x p e r i m e n t a l d i e t on the i n t a k e of n u t r i e n t s t h a t showed l a r g e i n t e r s u b j e c t v a r i a b i l i t y , such as v i t a m i n A , C and B12 (Tabl e I I ) . The changes i n n u t r i e n t i n t a k e s a s s o c i a t e d w i t h the r e s t r i c t e d p r o t e i n d i e t d i d not seem t o a f f e c t the group's g e n e r a l d i e t a r y s t a t u s , s i n c e i n t a k e of most n u t r i e n t s remained s i m i l a r t o o r above t h e RNIs (Tabl e I I ) . These e s t i m a t e s were based on d a t a from 12 fo o d r e c o r d s p e r s u b j e c t , which i s c o n s i d e r e d s u f f i c i e n t t o r e f l e c t a c c u r a t e l y the average i n t a k e of most n u t r i e n t s d u r i n g the 6-week d i e t p e r i o d . The o n l y n u t r i e n t t h a t appeared t o p r e s e n t a problem i n comparison w i t h the RNI was c a l c i u m i n females (Ta b l e I I ) . The s i g n i f i c a n t r e d u c t i o n s i n mean i n t a k e s of p r o t e i n , c a l c i u m , and o t h e r n u t r i e n t s on the e x p e r i m e n t a l d i e t can p r i m a r i l y be a t t r i b u t e d t o a d e c r e a s e i n t o t a l consumption of h i g h p r o t e i n f o o d s . To p r e v e n t t h i s from happening, the p a r t i c i p a n t s were encouraged t o i n c r e a s e t h e i r u s u a l i n t a k e of h i g h p r o t e i n foods i n the l a t t e r p a r t of t h e day. However, t h e y appeared t o have d i f f i c u l t y d o i n g t h i s . I t can be seen from T a b l e I I I , by s u b t r a c t i n g mean daytime from mean t o t a l p r o t e i n i n t a k e , t h a t mean evening p r o t e i n i n t a k e d i d not i n c r e a s e s u b s t a n t i a l l y from the r e g u l a r d i e t p e r i o d t o the r e s t r i c t e d p r o t e i n d i e t p e r i o d ( i . e . 41, 47 and 47 g p r o t e i n f o r r e c o r d i n g p e r i o d s 1, 2 and 3 r e s p e c t i v e l y ) . Some p a r t i c i p a n t s e x p r e s s e d a d i f f i c u l t y i n i n c r e a s i n g p a t i e n t s ' f o o d i n t a k e i n t h e e v e n i n g ( T a b l e s VII and I X ) . 51 These r e s u l t s show t h a t t h i s group of p a t i e n t s was a b l e t o m a i n t a i n an adequate i n t a k e of most n u t r i e n t s w h i l e on t h e r e s t r i c t e d p r o t e i n d i e t . However, the f i n d i n g s suggest t h a t i n i n d i v i d u a l s whose r e g u l a r d i e t i s m a r g i n a l l y adequate and p a r t i c u l a r l y whose i n t a k e of h i g h p r o t e i n foods i s moderate, the r e s t r i c t e d p r o t e i n d i e t might compromise the a b i l i t y t o meet n u t r i e n t needs. Evaluation of the validity of the 6-day record method S i n c e the p r e s e n t s t u d y i n v o l v e d f r e e - l i v i n g i n d i v i d u a l s , d i r e c t v a l i d a t i o n of the 6-day r e c o r d method c o u l d not be performed. The f i n d i n g s from a study by G e r s o v i t z et a l . (1978) suggested t h a t a l a c k •of m o t i v a t i o n on the p a r t of the s u b j e c t s may c o n t r i b u t e t o a g r a d u a l l o s s of a c c u r a c y i n r e c o r d k e e p i n g over t i m e . The f o l l o w i n g o b s e r v a t i o n s l e a d t o the b e l i e f t h a t the 11 p a r t i c i p a n t s i n t h i s study m a i n t a i n e d a h i g h l e v e l of a c c u r a c y i n c o m p l e t i n g f o o d r e c o r d s . G iven t h e c o n s i d e r a b l e amount of time and e f f o r t t h a t the p a r t i c i p a n t s i n v e s t e d i n t h i s study, i t can be s t a t e d t h a t t h o se who completed t h e study were h i g h l y m o t i v a t e d and c o o p e r a t i v e i n d i v i d u a l s . A l l s u b j e c t s completed 18 days of f o o d r e c o r d s and " o n - o f f " c h a r t s , a c c o r d i n g t o a s t r i c t s c h e d u l e and were c o n s i s t e n t l y on time f o r a l l appointments t o the U n i v e r s i t y H o s p i t a l . S u b j e c t s and s u p p o r t e r s had a d i r e c t i n t e r e s t i n the outcome of t h e st u d y and sha r e d the f e e l i n g ' t h a t t h e i r c o n t r i b u t i o n would e v e n t u a l l y b e n e f i t o t h e r i n d i v i d u a l s w i t h P a r k i n s o n ' s d i s e a s e . The v e r y low drop-out r a t e c o n f i r m s t h e s u b j e c t s ' 52 d e d i c a t i o n t o the study. The p a r t i c i p a n t s i n t h i s study were p o s s i b l y more s o c i a l l y i n v o l v e d and o u t g o i n g than would be a r e p r e s e n t a t i v e sample of P a r k i n s o n ' s d i s e a s e p a t i e n t s i n the community. A number of o b s e r v a t i o n s emerged d u r i n g the c o u r s e of the study r e g a r d i n g d a t a c o l l e c t i o n a t home. The m a r r i e d s u b j e c t s , and p a r t i c u l a r l y the men, b e n e f i t e d from a n o t i c e a b l e support from t h e i r spouse. Indeed, i t was u s u a l l y the w i f e , whether she was the s u b j e c t o r the s u p p o r t e r , who r e c o r d e d f o o d i n t a k e . T h i s might have enhanced the a c c u r a c y of the men's r e p o r t s s i n c e i n g e n e r a l the wives a l s o p r e p a r e d t h e f o o d . The m a j o r i t y of foods consumed by the s u b j e c t s were p r e p a r e d and consumed a t home. The female s u b j e c t who l i v e d i n a n u r s i n g home r e c e i v e d remarkable a s s i s t a n c e from the chef and the n u r s i n g s t a f f i n r e c o r d i n g f o o d i n t a k e d a t a . A f t e r each meal, t h e chef r e v iewed and i f n e c e s s a r y supplemented the i n f o r m a t i o n a l r e a d y e n t e r e d by the p a t i e n t i n the f o o d i n t a k e r e c o r d . EFFECT OF THE RESTRICTED^PROTEIN DIET ON BODY WEIGHT : ' The r e s u l t s showed t h a t a m a r g i n a l l y s i g n i f i c a n t r e d u c t i o n i n average body weight o c c u r r e d d u r i n g the f i r s t two weeks of daytime p r o t e i n r e s t r i c t i o n . A n a l y s i s of week two d i e t a r y r e c o r d s r e v e a l e d a s l i g h t a l t h o u g h not s i g n i f i c a n t r e d u c t i o n i n mean energy i n t a k e compared w i t h p r e - d i e t i n t a k e ( r e c o r d i n g p e r i o d two i n T a b l e I I I ) . I t i s p o s s i b l e t h a t more severe r e s t r i c t i o n s i n f o o d i n t a k e o c c u r r e d d u r i n g 53 week one, as the s u b j e c t s were " a d a p t i n g " t o the e x p e r i m e n t a l d i e t , which might have been r e s p o n s i b l e f o r the weight l o s s . T h i s h y p o t h e s i s can not be v e r i f i e d s i n c e f o o d r e c o r d s were completed d u r i n g week two o n l y . Maintenance of average body weight over the r e m a i n i n g f o u r week p e r i o d i n d i c a t e d t h a t the s u b j e c t s ' energy i n t a k e was adequate. EFFECT OF THE RESTRICTED PROTEIN DIET ON PARAMETERS OF PROTEIN AND IRON STATUS E x a m i n a t i o n of hemoglobin and serum albumin v a l u e s ( T a b l e V ) , i n d i c a t e s t h a t the i r o n and p r o t e i n s t a t u s of t h i s group of i n d i v i d u a l s were adequate a c c o r d i n g t o the s t a n d a r d s f o r t h e n u t r i t i o n a l assessment of the e l d e r l y ( C l a r k and B l a c k b u r n 1983, P a t t e r s o n e t a l . 1985). Average serum p r e a l b u m i n and f e r r i t i n l e v e l s were comparable t o those found i n a group of 279 h e a l t h y f r e e - l i v i n g e l d e r l y males and females l i v i n g i n the USA (McGandy e t a l . 1986). These f i n d i n g s a r e c o n s i s t e n t w i t h the d i e t a r y d a t a r e p o r t e d above. An a d v e r s e impact of t h e e x p e r i m e n t a l d i e t on the group's p r o t e i n and i r o n s t a t u s would have r e s u l t e d p r i m a r i l y i n a r e d u c t i o n of the two most s e n s i t i v e parameters, serum p r e a l b u m i n and f e r r i t i n r e s p e c t i v e l y . None of t h e parameters measured i n t h i s group of s u b j e c t s was n e g a t i v e l y a f f e c t e d by the s i x week daytime r e s t r i c t e d p r o t e i n d i e t . These f i n d i n g s a r e i n agreement w i t h the f a c t t h a t mean i n t a k e of energy, p r o t e i n and i r o n appeared t o remain adequate, d e s p i t e s i g n i f i c a n t drops i n p r o t e i n and i r o n i n t a k e s . 54 U n e x p e c t e d l y , a s i g n i f i c a n t i n c r e a s e i n serum f e r r i t i n was observed over time. T h i s phenomenon d i d not appear t o r e s u l t from an i n c r e a s e i n i r o n a b s o r p t i o n s i n c e , a c c o r d i n g t o f o o d r e c o r d a n a l y s i s , i r o n i n t a k e was reduced and v i t a m i n C i n t a k e remained unchanged throughout the r e s t r i c t e d p r o t e i n d i e t p e r i o d ( T a b l e I I I ) . The s i g n i f i c a n c e of t h i s o b s e r v a t i o n i s u n c l e a r and may r e f l e c t an i n c o n s i s t e n c y i n the f e r r i t i n a n a l y s i s p r o c e d u r e . EFFECT OF THE RESTRICTED PROTEIN DIET ON PERCENT TIME "ON" Three of e l e v e n s u b j e c t s demonstrated a s i g n i f i c a n t i n c r e a s e i n p e r c e n t time "on" w h i l e on the r e s t r i c t e d p r o t e i n d i e t ( T a b l e I V ) . T h e i r daytime p r o t e i n i n t a k e p e r kg body weight was not s i g n i f i c a n t l y d i f f e r e n t t h a n the o t h e r s u b j e c t s ' i n t a k e , which i n d i c a t e s t h a t non-r e s p o n d e n t s were not l e s s c o m p l i a n t t o the d i e t than r e s p o n d e n t s . The f a c t t h a t improvement was s u s t a i n e d over a p e r i o d of s i x weeks suggests t h a t the changes were i n d u c e d by a t r e a t m e n t e f f e c t r a t h e r t h a n a p l a c e b o e f f e c t . In a d o u b l e - b l i n d study ( T s u i e t a l . 1989), seven out of t e n s u b j e c t s w i t h u n p r e d i c t a b l e f l u c t u a t i o n s s i g n i f i c a n t l y i n c r e a s e d t h e i r p e r c e n t a g e of "on" hours when l i m i t e d t o below seven grams p r o t e i n i n t a k e d u r i n g daytime, compared t o more " t y p i c a l " i n t a k e . The d i s c r e p a n c y i n t h e i n d i v i d u a l s u c c e s s r a t e between T s u i e t a l . ' s study and the p r e s e n t study c o u l d be due t o the f a c t t h a t the f r e e - l i v i n g s u b j e c t s were e s t i m a t e d t o consume a p p r o x i m a t e l y t w i c e the amount of 55 p r o t e i n t h a n the i n - h o s p i t a l s u b j e c t s d u r i n g daytime ( i . e . average of about 13g v e r s u s <7g). These r e s u l t s a r e c o n s i s t e n t w i t h the h y p o t h e s i s t h a t even moderate i n c r e a s e s i n plasma LNAAs w i l l a f f e c t the f l u x of levodopa i n t o the b r a i n ( D a n i e l e t a l . 1976). A l t h o u g h o n l y t h r e e out of e l e v e n s u b j e c t s showed a s t a t i s t i c a l l y s i g n i f i c a n t i n c r e a s e i n p e r c e n t time "on", i t i s i n t e r e s t i n g t o note t h a t s e v e r a l o t h e r s showed a tendency towards improvement ( T a b l e IV) and t h a t s u b j e c t i v e l y , s i x out of e l e v e n b e l i e v e d t h a t t h e i r o v e r a l l daytime m o b i l i t y was improved as a r e s u l t of the r e s t r i c t e d p r o t e i n d i e t ( T a b l e V I ) . A few s u b j e c t s complained of a worsening of t h e i r daytime symptoms (T a b l e V I ) ; however, none seemed t o have e x p e r i e n c e d a r e d u c t i o n i n p e r c e n t time "on" ( T a b l e I V ) . Perhaps, i n c r e a s e s i n d y s k i n e s i a were p e r c e i v e d as i n c r e a s e s i n the s e v e r i t y of p a r k i n s o n i a n symptoms, a l t h o u g h attempts were made t o e x p l a i n t h e d i f f e r e n c e s between the two c o n d i t i o n s . I t i s a l s o p o s s i b l e t h a t d i s s a t i s f a c t i o n w i t h the d i e t r e s u l t e d i n a g e n e r a l f e e l i n g of d i s c o m f o r t , which was i n t e r p r e t e d by t h e s u b j e c t s as a worsening of t h e i r c l i n i c a l c o n d i t i o n . T h i s c o n j e c t u r e i s s u p p o r t e d by the f a c t t h a t none of the s u p p o r t e r s noted a worsening of the p a t i e n t s daytime symptoms (Table V I I I ) . R i l e y and Lang (1988) r e p o r t e d t h a t 60% of a group of f r e e - l i v i n g p a t i e n t s i n c r e a s e d t h e i r p e r c e n t a g e of "on" hours i n response t o a daytime r e s t r i c t i o n i n d i e t a r y p r o t e i n . However, s i n c e no s t a t i s t i c a l a n a l y s i s was r e p o r t e d , t h e i r r e s u l t s cannot be compared w i t h the p r e s e n t study. The f i n d i n g s of t h i s study suggest t h a t t h e r e s u l t s o b t a i n e d i n c o n t r o l l e d s t u d i e s can be d u p l i c a t e d i n f r e e - l i v i n g p o p u l a t i o n s , w i t h a lower r a t e of s u c cess however. COMMENTS ON THE APPLICATION OF THE RESTRICTED PROTEIN DIET TO FREE-LIVING INDIVIDUALS The r e s t r i c t e d p r o t e i n d i e t was d e s i g n e d t o l i m i t p r o t e i n i n t a k e t o lOg p r i o r t o the e v e n i n g meal. Based on d i e t a r y r e c o r d a n a l y s i s , average daytime p r o t e i n consumption was s i g n i f i c a n t l y r e d u c e d from 35 t o 12g i n females and from 37 t o 14g i n males. A l t h o u g h average daytime p r o t e i n i n t a k e was s l i g h t l y h i g h e r than p l a n n e d , i t i s s p e c u l a t e d t h a t the l e v e l s a c t u a l l y consumed would be d i f f i c u l t t o m a i n t a i n f o r most f r e e - l i v i n g p a t i e n t s on a l o n g - t e r m b a s i s . While on the r e s t r i c t e d p r o t e i n d i e t , a m a j o r i t y of s u b j e c t s c o n s i s t e n t l y complained of a f e e l i n g of hunger p r i o r t o the e v e n i n g meal, as w e l l as a l a c k of v a r i e t y i n f o o d c h o i c e s ( T a b l e s VI and V I I ) . The s p e c i a l low p r o t e i n p r o d u c t s , made w i t h s t a r c h s u b s t i t u t e d f o r f l o u r , c o u l d have r e p r e s e n t e d a p a r t i a l s o l u t i o n t o the s u b j e c t s ' c o m p l a i n t s . However, a c c e p t a n c e of such p r o d u c t s was v e r y poor and most s u b j e c t s were r e l u c t a n t t o use them ( T a b l e s VI and V I I ) . These f i n d i n g s suggest t h a t the use of the s p e c i a l low p r o t e i n p r o d u c t s s h o u l d remain o p t i o n a l and demonstrate the importance of d e v e l o p i n g a wider s e l e c t i o n of f o o d and r e c i p e s u g g e s t i o n s adapted t o the s p e c i f i c r e q u i r e m e n t s of the r e s t r i c t e d p r o t e i n d i e t . 57 At the end of the e x p e r i m e n t a l p e r i o d , about 50% of the s u b j e c t s s t a t e d t h a t t h e y would keep f o l l o w i n g the d i e t a t home ( T a b l e V I ) . A p p r o x i m a t e l y the same p r o p o r t i o n of p a t i e n t s s u b j e c t i v e l y n o t e d an improvement i n t h e i r daytime m o b i l i t y ( T a b l e V I ) . T h e r e f o r e , i t appears t h a t s u b j e c t i v e b e n e f i t i s an e s s e n t i a l c o n d i t i o n f o r l o n g-term adherence t o the d i e t . 58 VI. CONCLUSION The r e s u l t s of t h i s study show t h a t o t h e r w i s e h e a l t h y and h i g h l y m o t i v a t e d i n d i v i d u a l s w i t h P a r k i n s o n ' s d i s e a s e can m a i n t a i n adequate d i e t a r y i n t a k e s w h i l e on the r e s t r i c t e d p r o t e i n d i e t . However, i t i s s uggested t h a t i n i n d i v i d u a l s whose r e g u l a r d i e t i s m a r g i n a l l y adequate, the r e s t r i c t e d p r o t e i n d i e t might compromise n u t r i e n t i n t a k e s . To c o r r o b o r a t e the p r e s e n t f i n d i n g s , a d d i t i o n a l l o n g - t e r m n u t r i t i o n a l s t u d i e s s h o u l d be conducted on p a t i e n t s who o b t a i n a s u b j e c t i v e b e n e f i t from the r e s t r i c t e d p r o t e i n d i e t and who a r e w i l l i n g t o adhere t o the d i e t over an extended p e r i o d of t i m e . A l t h o u g h o n l y s u b j e c t i v e measures of motor performance were used ("on-off" c h a r t s and q u e s t i o n n a i r e s ) , i t appeared t h a t some p a t i e n t s b e n e f i t e d from the lowered daytime p r o t e i n i n t a k e s . The f a c t t h a t s e v e r a l s u b j e c t s wanted t o m a i n t a i n the d i e t suggests t h a t the g u i d e l i n e s t h a t were d e v e l o p e d f o r t h i s study c o u l d be s u c c e s s f u l l y used w i t h o t h e r m o t i v a t e d f r e e - l i v i n g P a r k i n s o n ' s d i s e a s e p a t i e n t s . P r a c t i c a l measures t h a t c o u l d be taken t o improve a c c e p t a n c e of the d i e t a r e : 1) To d e v e l o p v e r y low p r o t e i n r e c i p e s u s i n g a v a i l a b l e p r o d u c t s such as s t a r c h , n o n - d a i r y p r o d u c t s , sugar, o i l e t c . and 2) t o e l a b o r a t e the l i s t of l u n c h and snack s u g g e s t i o n s . Recommendations f o r i m p l e m e n t a t i o n : 1. The'use of the r e s t r i c t e d p r o t e i n d i e t s h o u l d be l i m i t e d t o P a r k i n s o n ' s d i s e a s e p a t i e n t s who have u n p r e d i c t a b l e response 59 f l u c t u a t i o n s t o levodopa. Other p a t i e n t s can not be e x p e c t e d t o b e n e f i t from lowered p r o t e i n consumption. 2. A l l p a t i e n t s who wish t o undertake a daytime r e s t r i c t e d p r o t e i n d i e t s h o u l d be c o u n s e l l e d by a r e g i s t e r e d d i e t i t i a n . Only those whose r e g u l a r d i e t s a r e e s t i m a t e d t o be h i g h l y adequate s h o u l d be i n s t r u c t e d on the d i e t . 3. P a t i e n t s s h o u l d be i n o t h e r w i s e r e l a t i v e l y good h e a l t h and not be f o l l o w i n g a n o t h e r se v e r e t h e r a p e u t i c d i e t . 4. I f no s u b j e c t i v e b e n e f i t i s p e r c e i v e d w i t h i n the f i r s t week of adherence t o daytime p r o t e i n r e s t r i c t i o n , the d i e t s h o u l d be d i s c o n t i n u e d . 5. I t i s recommended t h a t p r o t e i n and i r o n s t a t u s , as w e l l as body weight be r e g u l a r l y m o n i t o r e d i n p a t i e n t s f o l l o w i n g t h e r e s t r i c t e d p r o t e i n d i e t over extended p e r i o d s of t i m e . 6. Consumption of n u t r i t i o n a l l y complete f o r m u l a t i o n s (e.g. ENSURE) s h o u l d be encouraged i f e v e n i n g f o o d i n t a k e i s not h i g h . 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Nutr. 50:155-167 . 63 N u t r i t i o n Canada. 1973. N u t r i t i o n a n a t i o n a l p r i o r i t y ; a r e p o r t by N u t r i t i o n Canada t o the Department of N a t i o n a l H e a l t h and W e l f a r e . Ottawa: I n f o r m a t i o n Canada. Nutt J.G., W. R. Woodward, J . P. Hammerstad, J . H. C a r t e r , and J.L. Anderson. 1984. The " o n - o f f " phenomenon i n P a r k i n s o n ' s d i s e a s e . N. Engl. J. Med. 310:483-488. P a t t e r s o n , C , I.D. T u r p i e , and A.M. Benger. 1985. Assessment of i r o n s t o r e s i n anemic g e r i a t r i c p a t i e n t s . J. Am. Geriatr. Soc. 33:764-767. P i n c u s , J.H., and K.M. B a r r y . 1987a. D i e t a r y method f o r r e d u c i n g f l u c t u a t i o n s i n P a r k i n s o n ' s d i s e a s e . Yale J. Biol. Med. 60:133-137. P i n c u s , J.H., and K.M. B a r r y . 1987b. I n f l u e n c e of d i e t a r y p r o t e i n on motor f l u c t u a t i o n s i n P a r k i n s o n ' s d i s e a s e . Arch. 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S t a t i s t i c a l r e a s o n i n g f o r the b e h a v i o r a l s c i e n c e s , 2nd e d i t i o n . Needham, M a s s a c h u s e t t s : A l l y n and Bacon i n c . . T i m i r a s , M.-L., and H. B r o w n s t e i n . 1987. P r e v a l e n c e of anemia and c o r r e l a t i o n of hemoglobin w i t h age i n a g e r i a t r i c s c r e e n i n g c l i n i c p o p u l a t i o n . J. Am. Geriatr. Soc. 35:639-643. T s u i , J.K., S. Ross. K. P o u l i n , J . Douglas, D. P o s t n i k o f f , S. C a l n e , W. Woodward, and D.B. C a l n e . 1989. The e f f e c t of d i e t a r y p r o t e i n on the e f f i c a c y of L-dopa: A d o u b l e - b l i n d study. Neurology 39:54 9-552. Tuten, M.B., S. Wogt, F. Dasse, and 2. L e i d e r . 1985. U t i l i z a t i o n of p r e a l b u m i n as a n u t r i t i o n a l parameter. J. Parent. Ent. Nutr. 9:709-711. W i l k i n s o n , L. 1989. SYSTAT: The system f o r s t a t i s t i c s . Evanston, I l l i n o i s : SYSTAT, I n c . Young, C M . 1981. D i e t a r y methodology. In A s s e s s i n g changing f o o d c o n s u m p t i o n - p a t t e r n s . Washington, D . C : N a t i o n a l Academy Pr e s s pp 89-118. 65 APPENDIX 1 RECRUITMENT LETTER TO SUBJECTS 66 APPENDIX 2 CONSENT FORM HOW THIS STUDY WILL BE DONE Pri o r to the beginning of the study, you w i l l be asked short seri e s of questions to test your memory. If you agree to p a r t i c i p a t e i n t h i s study, you w i l l have to follow a 6 week r e s t r i c t e d protein d i e t on wich you w i l l be instructed during a daytime v i s i t to the University Hospital. P r i o r to s t a r t i n g on t h i s special d i e t we w i l l ask you to record everything you eat and drink f o r a 6 day period, while on your usual diet. During those 6 days, you w i l l also have to record on a chart the number of hours you are "on" (mobile) and the number of hours you are " o f f " (frozen). You w i l l be instructed on how to record your food intake and how to f i l l i n the "on-off" chart during a f i r s t v i s i t to the University Hospital. During the second and the s i x t h week on the special diet you w i l l be asked , once again to record your food intake and to f i l l i n the "on-off" chart, each time for a 6 day period. At the beginning and at the end of the 6 week period on the r e s t r i c t e d protein d i e t , blood samples w i l l be taken from you to measure d i f f e r e n t indicators of your n u t r i t i o n a l status. Afte r 2 and 6 weeks on the special diet, you and your supporter w i l l be asked to f i l l i n a questionnaire about your perception of the d i e t : your enjoyment of the diet, i t s e f f i c i e n c y , the problems encountered etc.. You w i l l have to dedicate 8 weeks to the project: 2 weeks on your usual d i e t and 6 weeks on the special d i e t . During that period of time, you and your supporter w i l l have to come to the University Hospital on 4 occasions fo r daytime v i s i t s : at the beginning, aft e r 2 weeks, af t e r 4 weeks and at the end (after 8 weeks). RISKS AND INCONVENIENCES During the f i r s t days on the r e s t r i c t e d protein d i e t you may experience incresingly severe side-effects from your medication. If t h i s happens, nothing i s wrong, i t simply means that the d i e t i s "working well". However, you w i l l have to contact the U.B.C. Movement Disorders C l i n i c as soon as possible for dosage adjustment (228-7660). CONFIDENTIALITY Much of the information obtained from t h i s study w i l l eventually be used i n s c i e n t i f i c publications, but the patients' i d e n t i t i e s w i l l not be revealed i n such publications. The results w i l l be available to the investigators. C o n f i d e n t i a l i t y w i l l be maintained by the normal process of health record maintenance at the University Hospital, U.B.C. Site. 70 FINANCIAL PAYMENT No f i n a n c i a l payment w i l l be offered i n t h i s study. The investigator or his designate has answered a l l your questions. I f you have additional questions during the course of the study, or i f any problem ar i s e , you may address them to any of the above mentioned investigators, I have been given the opportunity to discuss pertinent aspects of the research study, to ask questions, and hereby consent to p a r t i c i p a t e i n the project outlined. I acknowlege receipt of a copy of t h i s consent form. Patient's signature Date Investigator's signature Date Witness's signature Date 71 A P P E N D I X 3 MINI-MENTAL STATE EXAMINATION FORM 72 MINI-MENTAL STATE PATIENT DATE EXAMINER , EXAMINATION t B A S I C MEMORY TEST FOR NEUROPSYCHOLOGY Registration . _ — 6 MINI-MENTAL SCORE Name 3 objects: 1 second to say each- Then ask the patient a l l 3 a f t e r you have said thea. Cive 1 point for each c o r r e c t answer. Then repeat then unt i l he learns a l l 3-Count t r i a l s and record. T r i a l s Attention and Calculat ion S e r i a l 7 's . 1 point for each correct. Stop after 5 answers. A l t e r n a t i v e l y spe l l "world" 'backwards. Recal l /3 Ask for the 3 objects repeated above. Cive 1 point for each c o r r e c t . IF PATIENT FAILS TO REMEMBER ALL THREE OBJECTS, CONTINUE BELOW "Repeat these words after me and remember them, I will ask you for there later: HAT, CAR, TREE, TWENTY-SIX.* Orientation Vhat i s the (year) (season) (date) (day) (month)? / 5 Where are we: (province) (c i ty) (hospital) ( f loor)? "What were those words that I asked you to remember?* HAT C A R TREE TWENTY-SIX REMAINDER OF POLSTEIN MINI-MENTAL STATE  Language Name a p e n c i l , and watch (2 points) Repeat the following "No i f s , ands or buts" (1 point) . Follow a 3-stage conaand: "Take a paper in your right hand, fold i t in half and put i t on the floor" (3 points) . Read and obey the following: CLOSE YOUR EYES (1 point) Write a sentence (1 point) . Copy design (1 point) / 9 TOTAL MINI-MENTAL SCORE / 2 9 A s s e s s l e v e l o f c o n s c i o u s n e s s a l o n g a c o n t i n u u 72 A l e r t Drowsy S t u p o r Com APPENDIX 4 LETTER TO GENERAL PRACTITIONER 74 APPENDIX 5 CERTIFICATE OF APPROVAL FROM THE CLINICAL SCREENING COMMITTEE FOR RESEARCH AND OTHER STUDIES INVOLVING HUMAN SUBJECTS 76 A P P E N D I X 6 INSTRUCTIONS FOR KEEPING A SIX DAY FOOD RECORD 78 Food Record Name: Diet: Please keep a record of everything you eat and drink on the attached form for the following period: Read these instructions c a r e f u l l y before you s t a r t to write: 1. Write down everything vou eat and drink (including alcohol). Be sure to include a l l snacks. Record immediately aft e r each meal or snack to ensure accuracy. 2. Write down how much you eat and drink. 3. Use volume measures (cups, Tbsp, tsp, or mis) for cereals, r i c e , pasta, vegetables, canned or s l i c e d f r u i t s , beverages, peanut butter, mayonnaise, salad dressing, butter, margarine, sauces, gravies, soups, sugar, honey, jam etc. 4. Use cooked weights (ounces or grams) for meat, f i s h , poultry, cheese. Use the attached diagrams and labels on packaging to determine weight. The weight of meat, poultry and fish decreases by about 25% with cooking. Examples: - 4 oz. raw beef shrinks to 3 oz. cooked beef - 6 oz. raw cod shrinks to 4.5 oz. cooked cod 5. Use s i z e for raw f r u i t s , muffins, buns, crackers, cakes, pies, cookies, desserts etc. Give dimensions (eg 1 oatmeal cookie, 2" diameter) or specify small, medium or large based on the attached models. 6. Be s p e c i f i c about the type of food, brand name i f applicable and content of mixed dishes. For example: Time Food 12.30PM 2% milk (lunch) whole wheat bread butter omelette - eggs medium - cheddar cheese - vegetable o i l digestive cookies (Dare's) 7. Don't forget the extras 1 For example: sugar on your cereal dressing on your salad 79 Amount 1/2 cup 2 s l i c e s 2 tsp 1 1/2 ounce 2 tsp 2 D i a g r a m s o f M e a t , f o u l t r y . F l s b , and C h „ „ to H e l p Y o u E s t i m a t e C o o k e d W e l , h t , CHICKEN LEG ( cooked ) 3 o u n c e s l e a n f l e s h ( t h i g h e q u a l s 2 o u n c e s ) ( d r u m s t i c k e q u a l s 1 o u n c e ) 4 ounce s k i n p l u s fa t CHICKEN BREAST ( cooked ) 1 o u n c e s ' l e a n f l e s h 14 o u n c e s s k i n p l u s f a t (photoreduced by 30%) CHICKEN WINC ( c o o k e d ) H ounce l e a n f l e s h S ounce s k i n p l u s f a t HAMBURGER PATTT ( c o o k e d ) One h a m b u r g e r p a t t y t h i s t h i c k - y 1» e q u a l t o 3 o u n c e * . One h a a b u r g e r p a t t y t h i s t h i c k — , 1* e q u a l t o 2 o u n c e t . STEWING MEAT ( c o o k e d ) One p i e c e o f c o o k e d s i e v i n g a e a t t h i s s i z e I s e q u a l t o H o u n c e . (photoreduced by 30%) 82 S e a l * *nd : i i | : i u to Help Tou D e t e r a l n e S l x e t o f Rev F r u i t s , C r a c k e r s , Cake e t c APPENDIX 7 "ON-OFF" CHART "ON-OFF" CHART Name: Date: Diet: Day: SIND1ET Dose : Color: TIME 5 am 6 am 7 am 8 am 9 am 10 am 11 am 12 P" 1 P« 2 P" J P" 4 pm 5 pm 6 Pm 7 pm 8 P» 9 P" 10 pm 11 pm 12 am SInemot Intake "ON" "OFF" Lavel 1 or 2T RATIHQ aCAUS •ON" No tremor or s t i f f n e s s ( I . e . no Parkinson's disease symptoms), with or without d y s k i n e s i a ( I . e . i n voluntary,uncoordinated movements). (photoreduced by 15%) -"OPT" S t i f f n e s s or r i g i d i t y w i t h or without tremor. L e v e l 1: Remain Independent In c a r r y i n g out d a l l y a c t i v i t i e s . L e v e l 2: ReflUJXC. flaslatanCC i n c a r r y i n g out d a l l y a c t i v i t i e s , w i t h or without being bedridden or c h a i r bound. APPENDIX 8 GUIDELINES FOR THE RESTRICTED PROTEIN DIET 86 Department of Dietetics University Hospital, UBC Site RESTRICTED PROTEIN DIET FOR PARKINSON'S DISEASE PATIENTS The following diet is being used for experimental purposes only Name: Date: 87 General Guidelines 1) During daytime: low protein diet • Consume only those foods specified in your daytime meal plan (see list 1 and 2) • Take as much free foods (see list 2) as possible to prevent weight loss 2) From dinner until bedtime: high protein diet • No food restriction • Make sure that you eat the high protein foods (see list 3) that you have been avoiding during daytime 83 Daytime Meal Plan Breakfast (before 9:00am) • 1 fruit choice Menu Ideas (See list 1) (1) 1/2 cup orange juice • 1 starchy choice 1 slice bread, butter/jam (See list 1) coffee, sugar, non-dairy creamer • free foods (See list 2) (2) 1 /2 fresh grapefruit 1/2 cup cereal, sugar/non-dairy creamer tea with honey Low protein snack (I0:00-i0:30am) (Choose 1) • 1/2 cup canned fruits • 1/2 cup apple sauce with non-dairy whipped topping • 2 soda crackers with butter/jam • 1 small fruit • 1 small cookie Lunch (12:00-12:30pm) 2 starchy choices (See list 1) OR 1 starchy choice and 1 vegetable choice (See list 1) f r e e f o o d s (See list 2) Menu ideas 1) Vegetable Sandwich: 2 slices bread with butter, tomato/cucumber slices and mayonnaise 2) 1 cup cooked pasta seasoned with basil, garlic, butter; lettuce with dressing 3) 1 /2 cup vegetable soup and 1 slice bread with butter Low protein snack (after 2:30pm) (Choose 1) • 1/2 cup canned fruits • 1/2 cup apple sauce with non-dairy whipped topping • 2 soda crackers with butter/jam • 1 small fruit • 1 small cookie oo LIST1: Low Protein Foods i) Fruits and Vegetables Serving Size 1 vegetable choice equals; all vegetables (including potato and corn) 1/2 cup tomato sauce 1/2 cup tomato or vegetable juice 1/2 cup 1 fruit choice equals; fruit juice 1/2 cup fresh or canned fruits 1 medium or 1 /2 cup ii) Starchy Food Serving Size 1 choice equals; bread (white, whole wheat, etc.) 1 slice bagel 1/2 bun 1/2 pancake, waffle (5" diam) 1 muffin (medium) 1/2 crackers 4 pieces pasta 1/2 cup cereal 1/2 cup rice 1/2 cup 90 LIST 2: Free Foods Fats and oil Sweets Beverages Condiments and seasonings — Certain vegetables Miscellaneous butter, margarine, mayonnaise, salad dressing, non-dairy topping, non-dairy creamer, vegetable oil. sugar, honey, jam, jelly, syrup, hard candies, popsicles. coffee, tea, carbonated beverages, water, fruit drink powders. herbs, spices, salt, mustard, vinegar, flavouring extracts. lettuce, cucumber, celery, green pepper. bran 91 Dinner and Evening Meal Plan Dinner (after 5pm) No food restriction. Have a regular meal and make sure to include generous amounts of high protein foods (see list 3 ) Menu Idea • soup • meat (red meat, poultry, fish or alternates) • potato/rice/pasta • vegetables • milk (or milk product) • bread, butter/margarine • dessert Evening snack No food restriction. An evening snack will help you to increase your intake of protein. Make a special effort to have a snack before bedtime if you feel that you are losing weight. Snack ideas (choose 1 or more) • hot chocolate • bowl of cereal with milk • toast with cheese or peanut butter, etc. 92 LIST 3: High Protein Foods Milk and milk products — milk, buttermilk, evaporated milk, cheese, yogurt, ice cream, etc. Meat, fish and poultry — including cold cuts, bacon, sausages, sea foods, etc. Eggs Mixed dishes pizza, lasagna, hamburgers, macaroni and cheese, chili, etc. Meat alternates nuts (peanuts, pecans, cashews, etc.), peanut butter, seeds (sunflower seeds, sesame seeds, etc), beans (kidney, lima, etc.), lentils, etc. The following food items are high in protein but low in nutrition. Choose from the above categories first. Chocolate bars, cake, pastries, cookies, pie, diet products sweetened with Aspartame, gelatin, etc. 93 APPENDIX 9 PATIENTS' QUESTIONNAIRE 94 PATIENTS' QUESTIONNAIRE Rate each of the following items as perceived while on sp e c i a l d i e t (Worse) (As Usual) (Better) 1.Mobility: -Daytime -Evening -2 -2 -1 -1 0 0 1 1 2 2 If you have noticed any change(s) i n your mobility (whether better or worse), please describe the change(s): 2. Dyskinesia (involuntary movements): -Daytime -2 -Evening -2 3. General well-being -2 • 1 0 1 2 • 1 0 1 2 • 1 0 1 2 4. P r e d i c t a b i l i t y of motor status ( a b i l i t y to predict whether you w i l l be "on" or " o f f " at s p e c i f i c times during the day) -2 -1 5. Enjoyment of die t (taste) -2 -1 6. Hunger s a t i s f a c t i o n p r i o r to evening meal -2 -1 7. D i f f i c u l t y of meal planning -2 -1 8. Time involved i n meal preparation -2 -1 9. Average cost of food -2 -1 0 0 1 2 1 2 95 10. Would you follow t h i s d i e t over a long period of time? YES NO 11. Did you use special low protein products? YES NO A-If Yes, did t h e i r use help: -Improve mobility? YES NO -Your general well-being? YES NO - S a t i s f y hunger p r i o r to evening meal? YES NO -Meal planning? YES NO -Meal preparation? YES NO B-If no, please give reason(s)? 12. Do you think special low protein products are an ess e n t i a l part of t h i s diet? YES NO 13. What were the major d i f f i c u l t i e s encountered with the d i e t at home: 14.Any other comments? 96 APPENDIX 10 SUPPORTERS' QUESTIONNAIRE 97 SUPPORTERS' QUESTIONNAIRE Rate each of the following items as perceived while was on the sp e c i a l d i e t (Worse) (As usual) (Better) 1.Mobility: -Daytime - 2 - 1 0 1 2 -Evening - 2 - 1 0 1 2 If you have noticed any change(s) i n the patient's mobility (whether better or worse), please describe the change(s): 2. Dyskinesia (involuntary movements): -Daytime - 2 - 1 0 1 2 -Evening - 2 - 1 0 1 2 3. General well-being - 2 - 1 0 1 2 4. Patient's dependency on your care - 2 - 1 0 1 2 5. D i f f i c u l t y of meal planning - 2 - 1 0 1 2 6. Time involved i n meal preparation - 2 - 1 0 1 2 7. Average cost of food - 2 - 1 0 1 2 8. Would you encourage to follow t h i s d i e t over a long period of time? YES NO 98 9.Did use s p e c i a l low protein products? YES NO A-If yes, did t h e i r use help: -Improve mobility? YES NO -His or her general well-being? YES NO -Meal planning? YES NO -Meal preparation? YES NO -What were the special low protein products used? B-If no, please state reason(s)? 10. Do you think special low protein products are an e s s e n t i a l part of t h i s diet? YES NO 11. What were the major d i f f i c u l t i e s encountered with the d i e t at home: 12.Any other comments? 99 

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