UBC Theses and Dissertations

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UBC Theses and Dissertations

The antithyrogenic effect of thiamine, riboflavin, and pyridoxine on the basal metabolic rate, after… Goranson, Ewald Swan 1943

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The A n t i t h y r o g e n i e E f f e c t o f T h i a m i n e , R i b o f l a v i n , a n d P y r i d o x i n e on t h e B a s a l M e t a b o l i c R a t e , a f t e r I n d u c e d Hyperthyroidism hy  '  E w a l d Swan G o r a n s o n , B.A.  A Thesis submitted i n P a r t i a l F u l f i l m e n t of The R e q u i r e m e n t s f o r t h e Degree o f MASTER OF ARTS i n t h e Department o f , ZOOLOGY  The U n i v e r s i t y o f B r i t i s h O c t o b e r , 1943.  Columbia  ACKNOWLEDGMENTS  I w o u l d , l i k e t o express Dr.  my s i n c e r e  thanks,  J . A l l a r d y c e , u n d e r whose d i r e c t i o n t h i s r e s e a r c h was c a r r i e d o u t .  D r . W. A. C l e m e n s , f o r t h e i n t e r e s t t a k e n i n t h i s work. • P r o f e s s o r G» J . S p e n c e r , f o r . t h e ' e x a m i n a t i o n of s l i d e s o f g l a n d u l a r t i s s u e , which i t h a d been i n t e n d e d t o u s e i n t h i s w o r k , anffl t o Mr. K. S t a r k , f o r t h e p r e p a r a t i o n o f the s l i d e s . D r . W. J . L a i n g , S h a u g h n e s s y M i l i t a r y H o s p i t a l , .for information regarding t h y r o i d therapy and f o r a d e m o n s t r a t i o n o f t h e a p p a r a t u s u s e d i n m a k i n g B.M..R. d e t e r m i n a t i o n s .  iii  TABLE OF CONTENTS ' Page 1.  INTRODUCTION  1.  11. .. SURVEY  6.  A. I n d i c a t i o n s f o r t h e Use o f V i t a m i n B l , B2, and B6 S u p p l e m e n t s i n Hyperthyroidism a. Weight  Loss and A n o r e x i a  b. G l y c o l y s i s  6.  .  8»  c. T i s s u e L o s s o f V i t a m i n B l  9,  d. M e t a b o l i s m  9.  B. T o l e r a n c e t o t h e V i t a m i n s B 1 B 2 , and B6  10.  C. F a c t o r s G o v e r n i n g Rate  11.  ?  the Basal Metabolic  a. F a s t i n g  „  11.  b. E n v i r o n m e n t a l T e m p e r a t u r e -  12.  c. Time o f Day  22.  d. Age  III.  6.  ,  13.  e. B a r o m e t r i c P r e s s u r e .  13.  D. T h y r o i d P r e p a r a t i o n s a n d Manner o f Administration "  13.  EXPERIMENTAL  16.  A. A n i m a l s  16.  B. E n v i r o n m e n t  16.  C» D i e t  17.  D. S o u r c e o f T h y r o x i n a n d V i t a m i n s  '  17.  iv. Page E. The A p p a r a t u s  19.  a. M o d i f i c a t i o n s f r o m t h e O r i g i n a l  , .  Design  19.  b. O p e r a t i o n  23.  P. Measurement o f t h e B.M.R.  25.  G. Methods E m p l o y e d  28.  a. F a c t o r s I n f l u e n c i n g t h e B.M.R.  28.  • ', . 1. F a s t i n g 2. E n v i r o n m e n t a l  28. Temperature  3. Age  29..  '  29.  4. Time o f Day  30.  b. D e s i c c a t e d T h y r o i d  30.  1. A d m i n i s t e r e d  after Fasting  30.  2. A d m i n i s t e r e d  prior to Fasting  31.  c. V i t a m i n s B1,B2,B6,and l / l O G r a i n Thyroid  32.  d. V i t a m i n s B1,B2,B6, a n d -J- G r a i n Thyroid v  33.  e. C o n t r o l s  34.  RESULTS ( T a b l e s  a n d Graphs )  DISCUSSION  _35-49  incl.  ^50.  A. A n i m a l s  50.  B. A p p a r a t u s  50.  C. F a c t o r s A f f e c t i n g t h e B.M.R. a. F a s t i n g  51. 51.  b. T e m p e r a t u r e  52.  Page c. Age  54.  d. T i m e o f Day  55.  D. D e s i c c a t e d T h y r o i d  55.  a. A d m i n i s t e r e d  after Pasting  55.  b. A d m i n i s t e r e d  prior to Pasting  56.  E. V i t a m i n s a n d t h e T h y r o i d a.- V i t a m i n s B1,B2,B6 a n d l / l O G r a i n Thyroid  57.  b. V i t a m i n s B1,B2,.B6 and £ G r a i n Thyroid  58.  F. C o n t r o l s VI.  . 5 7 .  60.  SUMMARY 61.  V I I . REFERENCES  CITED  65.  THE ANTITHYROGENIC EFFECT OF THIAMINE,RIBOFLAVIN, AND PYRIDOXINE ON THE BASAL METABOLIC RATE,AFTER INDUCED HYPERTHYROIDISM INTRODUCTION ;  ~". .  The i n v e s t i g a t i o n o f v a r i o u s ficial  s u b s t a n c e s bene-  i n t h y r o i d t h e r a p y has c l a i m e d t h e a t t e n t i o n of a  l a r g e number o f w o r k e r s d u r i n g  the past t h i r t y years.  A  v e r y good summary o f t h i s w o r k , p r i o r t o 1 9 3 5 , h a s b e e n given  b y A.T.Cameron(6). Among t h e s u b s t a n c e s s t a t e d t o  have p r o d u c e d s a t i s f a c t o r y r e s u l t s a r e q u i n i n e ,  insulin,  a d r e n o c o r t i c a l hormone,potassium permanganate, sodium o r a m  m o n l u m f l u o r i d e , and c e r t a i n s a l t s o f c o p p e r , a r s e n i c  and  other minerals..Though e n t h u s i a s t i c claims  sporadically f o r t h e i r therapeutic hyperthyroid been  were made  use i n a l l e v i a t i n g the  c o n d i t i o n , most o f t h e s e c l a i m s  have  apparently  disputed. Other attempts t o t r e a t h y p e r t h y r o i d  by t h e r a p e u t i c thyroidectomized  conditions  m e a s u r e s i n c l u d e d t h e u s e o f serum o f a n i m a l s , o f myxedematous  patients,or the  "immune serum" f r o m g o a t s f e d t h y r o i d p r e p a r a t i o n s . underlying  The  p r i n c i p l e o f s u c h t h e r a p y was b a s e d on t h e f a c t  that the blood or t i s s u e s contained  a substance  t o t h e t h y r o i d p r i n c i p l e , a l t h o u g h d i v e r s e and views were h e l d  as t o t h e n a t u r e o f t h i s  antagonistic"  contradictory  antagonistic  p r i n c i p l e . Romeis(6) suggested that a s p e c i f i c p r o t e c t i v e compound does e x i s t . He f o u n d t h a t  i f he added b l o o d  along  w i t h thyroxine t o water c o n t a i n i n g tadpoles, the well-known metamorphosis and r e t a r d a t i o n o f growth produced by thyroxine •-"'did n o t a p p e a r . A d r i e d - b l o o d p r e p a r a t i o n h a s b e e n e m p l o y e d with b e n e f i c i a l r e s u l t s , although i o n s must be e n f o r c e d .  certain dietary restrict-  I f the treatment  i s specific, i t i s  d i f f i c u l t t o u n d e r s t a n d why d i e t a r y s t r i n g e n c y i s n e c e s s a r y . The  existence of a chalonic  mechanism(inhibitory  hormone) a c t i n g t o r e s t o r e a h y p e r t h y r o i d c o n d i t i o n t o n o r m a l was i n v e s t i g a t e d b y S t a r r a n d PomerenzeC^/) i n 1 9 4 1 . They o b s e r v e d t h a t a n o c c a s i o n a l c a s e o f h y p e r t h y r o i d i s m subsided But  r a p i d l y as t h o u g h such a mechanism were i n operation.  a t t e m p t s t o produce a c h a l o n e o f t h i s t y p e by t h e admin-  i s t r a t i o n of. d e s i c c a t e d t h y r o i d , t h y r o t r o p h i c hormone, vitamin A,vitamin  C, o r t e s t o s t e r o n e p r o p r i o n a t e  proved  ineffective. In medical  p r a c t i c e t o d a y , two m e a s u r e s a r e  g e n e r a l l y adopted i n t h e treatment  of a hyperthyroid  c o n d i t i o n . Severe cases a r e t r e a t e d by p a r t i a l a b l a t i o n of t h e gland, and l e s s severe  o r m i l d e r cases by t h e use  o f compounds o f i o d i n e , u s u a l l y L u g o l ' s  s o l u t i o n , which  contains potassium i o d i d e . Since thyroidectomy, while the basal metabolic  performed  r a t e i s h i g h , o f t e n proved  fatal,  p a t i e n t s s u f f e r i n g - f r o m Grave's d i s e a s e a r e u s u a l l y g i v e n i o d i n e i n some f o r m t o r e d u c e t h e m e t a b o l i c  rate  an o p e r a t i o n . I n some c a s e s , h o w e v e r , p r o l o n g e d operative treatment  w i t h Lugol's  before pre-  s o l u t i o n has been f o u n d  t o produce a r e f r a c t o r i n e s s t o i o d i n e ( & ) . A f t e r a  period  of twenty days the b e n e f i c i a l  e f f e c t s wear o f f , t h e  metabolic  the  r a t e i n c r e a s e s , and  symptoms o f t h e  t h y r o i d c o n d i t i o n r e t u r n . I n m i l d cases of the a c t i v e t h y r o i d c o n d i t i o n , a j u d i c i o u s use b e n e f i c i a l , but  there i s a recurrence  as soon as t h e t r e a t m e n t s t o p s . The  hyper-  over-  of i o d i n e i s  of' t h e  condition  p r e c i s e a c t i o n of  i o d i n e i n remedying the h y p e r t h y r o i d Grave's d i s e a s e , i s not y e t  basal  condition, particularly  understood.  D u r i n g the; l a s t d e c a d e an i n c r e a s i n g amount o f w o r k has  b e e n done on t h e a n t i t h y r o g e n i c a c t i o n o f t h e  vitamins.  The  review  B  of the l i t e r a t u r e , which f o l l o w s ,  g i v e s a f a i r l y comprehensive survey of t h i s work w h i c h i s concerned mainly countering  with'the  e f f e c t of the  weight l o s s , diminished  food  B vitamins  In  i n t a k e and  anorexia,  g l y c o l y s i s o f t h e l i v e r and b o d y t i s s u e s , and storage  o f t h e v i t a m i n s . The  the use  of the B vitamins  some c o t m t e r c l a i m s The B vitamins  the  tissue  work, i n the main, suggests  i n hyperthyroid  therapy,  although  a r e a l s o made.  argument a d v a n c e d h e r e i n f o r t h e u s e  i n combatting hyperthyroidism  i s that  of  favorable  r e s p o n s e t o t r e a t m e n t w i t h v i t a m i n s u p p l e m e n t s can e x p e c t e d o n l y when t h e d i s o r d e r has of a s p e c i f i c v i t a m i n o r v i t a m i n s Since  excessive  the  be  been caused by d e f i c i e n c y  or by i n a b i l i t y t o use  amounts o f t h y r o x i n s t i m u l a t e c a t a b o l i s m  t h e b o d y t i s s u e s and  p a r t i c u l a r l y of the  liver(main  them. of  storage  4. d e p o t o f t h e B v i t a m i n s w h i c h t h e body i s a b l e t o r e t a i n ) (8 )  , i t i s expected and has indeed  the B v i t a m i n s w i l l , destroyed.  been shown t h a t  a t t h e same t i m e , be d e p l e t e d o r  C o n s e q u e n t l y , t h e more t h y r o x i n e made a v a i l a b l e  i n t h e body, t h e g r e a t e r t h e requirement f o r t h e B v i t a m i n s . The  d i a g n o s t i c t e s t now g e n e r a l l y e m p l o y e d t o  c o n f i r m o r -disprove t h e e x i s t e n c e o f a t h y r o i d d i s e a s e i s the determination  of the basal metabolic  rate. In conditions  of h y p e r a c t i v i t y o f t h e t h y r o i d gland, t o t a l metabolism i s a c c e l e r a t e d i n p r o p o r t i o n t o t h e degree o f h y p e r t h y r o i d i s m . According  t o Hawk a n d B e r g e i m C ^ , t h e b a s a l m e t a b o l i c  does n o t e s t a b l i s h a d i a g n o s i s o f h y p e r t h y r o i d i s m ,  rate  but i n  the m a j o r i t y o f cases v a r i a t i o n s i n t h e B.M.R.(basal  metabolic  r a t e ) c a n be i n t e r p r e t e d a s v a r i a t i o n s i n t h e f u n c t i o n s o f t h e t h y r o i d g l a n d . A number o f d i s e a s e s , d i e t a r y f a c t o r s , and  environmental  conditions w i l l a f f e c t the basal  r a t e , b u t , a s s u m i n g t h a t no o t h e r d i s e a s e s and  the environmental  metabolic  are present,  conditions are conducive t o a basal  c o n d i t i o n , a y a r i a t i o n i n t h e B.M.R. i s i n d i c a t i v e o f a thyroid condition. I n o n l y one r e p o r t e d i n s t a n c e ( 3 ? ) h a s v i t a m i n B l been r e p o r t e d t o h a v e a l o w e r i n g e f f e c t  on t h e B.M.R. i n  a h y p e r t h y r o i d c o n d i t i o n and t h i s c l a i m has been d i s p u t e d ^ ) . The  present  i n v e s t i g a t i o n was u n d e r t a k e n t o d e m o n s t r a t e  the e f f e c t of the vitamins t h i a m i n e ! B l ) , r i b o f l a v i n ( B 2 ) , a n d " p y r i d o x i n e ( B 6 ) , s i n g l y and i n c o m b i n a t i o n ,  on t h e b a s a l  metabolic r a t e of the a l b i n o r a t a f t e r induced hyperthyroidism. M e t a b o l i s m i s r e g a r d e d a s b a s a l when t h e h e a t production^of  an i n d i v i d u a l i s m i n i m a l , and i s p r e s e n t  o n l y u n d e r c o n d i t i o n s I n v o l v i n g c o m p l e t e p h y s i c a l and m e n t a l r e l a x a t i o n , ,the c o m p l e t e a b s e n c e o f d i g e s t i v e a c t i v i t y , and when t h e e n v i r o n m e n t a l t e m p e r a t u r e i s s u c h as t o m i n i m i z e heat p r o d u c t i o n . revealed  A survey of, the  literature  the f a c t that the experimental conditions  under  . w h i c h m e t a b o l i s m i s b a s a l have n o t y e t been w e l l e s t a b l i s h e d f o r s t u d i e s on t h e w h i t e r a t . There i s s t i l l  some u n c e r t a i n t y  regarding: (I) the length of the f a s t i n g period before metabolism i s b a s a l . (ii) (iii)  the temperature of thermal n e u t r a l i t y . t h e age o f t h e r a t b e f o r e m e t a b o l i s m i s  constant. ( i v ) t h e i n f l u e n c e o f t h e '"diurnal f a c t o r on basal  metabolism. T h e s e f a c t o r s w e r e i n v e s t i g a t e d , p r i o r and  I n c i d e n t a l t o a^study o f t h e main problem, a l r e a d y  stated.  SURVEY I n d i c a t i o n s f o r t h e Use of V i t a m i n Supplements i n H y p e r t h y r o i d i s m  Bl,B2,andB6  :  a. W e i g h t L o s s a n d A n o r e x i a Among t h e e a r l i e s t  investigations into the  r e l a t i o n s h i p between t h e B v i t a m i n s and h y p e r t h y r o i d i s m ;  was t h a t o f H i m w i c k , G o l d f a r b a n d C o w g i l l U ^ ) They r e p o r t e d  i n 1931.  an i n c r e a s e i n t h e requirement o f undi-fferent  i a t e d v i t a m i n B by t h e dog d u r i n g i n t e r v a l s o f f e e d i n g d e s i c c a t e d t h y r o i d , as d e t e r m i n e d by t h e p e r i o d o f onset o f anorexia  and l o s s , o f body w e i g h t . C o w g i l l  and•Palmieri(y),  u s i n g d e s i c c a t e d t h y r o i d and. H a r r i s y e a s t  as a s o u r c e  o f v i t a m i n B, f o u n d ' s i m i l a r r e s u l t s w i t h  pigeons,i.e.,the  v i t a m i n B r e q u i r e m e n t p r o v e d t o be g r e a t e r i n h y p e r t h y r o i d ! than under normal c o n d i t i o n s . The  protective influence of the B vitamins  a g a i n s t w e i g h t l o s s a n d a n o r e x i a due t o t h y r o i d  feeding  was f u r t h e r d e m o n s t r a t e d b y S u r e and Smith(#7) i n 1934, u s i n g a l b i n o r a t s . They r e p o r t e d t h a t r e t a r d a t i o n o f l o s s o f w e i g h t c a n be s e c u r e d  i n animals,  r e c e i v i n g t o x i c doses  of pure c r y s t a l l i n e t h y r o x i n e ( i n t r a v e n o u s ) , b y t h e a d m i n i s t r a t i o n of a potent vitamin B l concentrate.  The  i s o l a t i o n o f B l i n p u r e c r y s t a l l i n e f o r m b y M e r c k and Go. made p o s s i b l e a q u a n t i t a i v e s t u d y and  of t h e problem. Sure  Buchanan(^50 f o u n d t h a t a d o s e o f 30 t o 100 gammas o f  p u r e B i was e f f e c t i v e i n c o u n t e r a c t i n g t h e t o x i c i t y o f as h i g h a d a i l y d o s e a s .2 mg. o f t h y r o x i n e . Drill had  a n d Sherwood(/<?) l i k e w i s e f o u n d t h a t  an a n t i t h y r o g e n i c e f f e c t I n o v e r c o m i n g a n o r e x i a and  weight .loss. Hyperthyroid yeast, regained t h y r o i d gland. to  thiamine  rats*  t r e a t e d w i t h v i t a m i n B l and  l o s t weight though s t i l l r e c e i v i n g t h e V i t a m i n B l and y e a s t  concentrate  was f o u n d  g r e a t l y stimulate the food i n t a k e . I n v e s t i g a t i n g the  caloric  Intake  and w e i g h t b a l a n c e  of hyperthyroid  dogs,  D r i l l ( / 4 ) f o u n d t h a t t h e f o o d i n t a k e o f - s i x d o g s , on a n o r m a l d i e t , i n c r e a s e d t o n e a r l y t w i c e n o r m a l when t h y r o i d f e e d i n g was s t a r t e d . A f t e r t h r e e weeks t h e f o o d i n t a k e showed a decline, suggesting a depletion of the stores o f the B v i t a m i n s . The i n j e c t i o n . o f B l r e s t o r e d t h e a p p e t i t e t o the previous- h y p e r t h y r o i d l e v e l , w i t h a r e s t o r a t i o n o f w e i g h t y When y e a s t was removed f r o m t h e n o r m a l d i e t o f h y p e r t h y r o i d dogs, t h e food i n t a k e dropped complete a n o r e x i a weight, D r i l l ( ^ )  sharply,  r e s u l t i n g i n some c'ases. A l l dogs obtained  t h e same r e s u l t s w i t h  lost  rats.  Rats f e d BI and t h y r o i d d i d n o t g a i n weight u n l e s s a r i c h source  o f B2 was added t o t h e d i e t . D r i l l  and Overman(/<£>)  r e p o r t e d t h a t t h e i n j e c t i o n o f B6 a n d c a l c i u m  pantothenate  r e p l a c e d t h i s a d d i t i o n o f B2. T h u s , i n a d d i t i o n t o t h i a m i n e , p y r i d o x i n e , r i b o f l a v i n and p a n t o t h e n i c to  a c i d were a l s o f o u n d  b e r e q u i r e d i n l a r g e amounts i n e x p e r i m e n t a l  thyroidism.  hyper-  8. b. G l y c o l y s i s Using a standard vitamin content, functions  Drill  d i e t , w i t h y e a s t ©f known  and Iiays(/5) s t u d i e d t h e l i v e r  o'f *dogs a t two l e v e l s o f t h y r o i d f e e d i n g . I n  some c a s e s t h e l i v e r was n o r m a l , i n o t h e r s  a b n o r m a l , when  v i t a m i n - B l was p r e s e n t i n t h e d i e t . I n a l l c a s e s t h e l i v e r was a b n o r m a l when t h e vitam'Ih was a b s e n t . D r i i l ( / 7 )  reported  t h a t r a t s r e c e i v i n g n o r m a l d i e t s c o n t a i n i n g 2.1 t o 2.4 i n t e r n a t i o n a l u n i t s o f B l a n d 2.4 t o 2.6 S h e r m a n - B o u r q u i n u n i t s o f v i t a m i n B2 t o g e t h e r  w i t h 1 mg. o f t h y r o x i n e ,  s u b c u t a n e o u s l y , p e r d a y , l o s t w e i g h t a n d showed l o w l i v e r glycogen values.  The same d i e t w i t h o u t t h e t h y r o x i n  r e s u l t e d i n weight gains  and normal l i v e r g l y c o g e n . Rats  f e d a n o r m a l d i e t w i t h 54 i n t e r n a t i o n a l u n i t s o f B l a n d 60 S h e r m a n - B o u r q u i n u n i t s t o g e t h e r  w i t h 1 mg. o f t h y r o i d -  d a i l y g a i n e d weight' o r remained a t a c o n s t a n t showed n o r m a l l i v e r g l y c o g e n  weight and  values.  Mamikawa(5^) d e m o n s t r a t e d t h a t t h e . h e i g h t e n e d . a c t i v i t i e s of t i s s u e r e s p i r a t i o n and g l y c o l y s i s I n t h e v i s c e r a , i n s t i g a t e d by thyroxine  a d m i n i s t r a t i o n , were  weakened f o l l o w i n g t h e a d m i n i s t r a t i o n o f t h y r o x i n s u p p l e m e n t e d w i t h B l . Kubo {H>l) showed t h a t promotes g l y c o g e n e s i s  i n healthy  thiamine  r a b b i t s . T h i s was f o u n d  t o be m a r k e d when t h e s t o m a c h was empty. In.some c a s e s o f diabetes,  the i n j e c t i o n of B l a l l e v i a t e d t o a great  extent  9« the hyperglycemia  and g l y c o s u r i a , f o l l o w i n g m e a l s .  S u p p l e e , B e n d e r and Hanford(^/3) h a v e r e c e n t l y reported that rats deficient  i n thiamine,  riboflavin,  pantothenic  a c i d and p y r i d o x i n e show an i n e f f i c i e n t  utilization  o f f o o d and i m p a i r e d  When a n i m a l s  i n the l i v e r .  were d e p l e t e d o f a n y one o f t h e s e  the others, a r i s e i n the l i v e r the'missing factor'was these  glycogenesis  glycogen  and g i v e n  r e s u l t e d when  s u p p l i e d . This demonstrated t h a t  v i t a m i n s a r e c o m p l e m e n t a r y t o one a n o t h e r a n d t h a t  e a c h may p a r t i c i p a t e i n t h e b u i l d i n g u p o f g l y c o g e n in  stores  the l i v e r .  c» T i s s u e L o s s o f B l D r i l l i / 3 ) d e m o n s t r a t e d t h a t r a t s r e c e i v i n g 12 gm. .of n o r m a l d i e t  t o g e t h e r w i t h 100 mg. o f t h y r o i d g l a n d  showed n o r m a l amounts o f B l i n t h e s p l e e n , a r e d u c t i o n i n the kidney  a n d a marked r e d u c t i o n i n t h e l i v e r ,  when  compared w i t h n o r m a l r a t s o n t h e same d i e t . When t h e d i e t was s u p p l e m e n t e d w i t h 500•gammas o f t h i a m i n e  p e r day, t h e  r a t s showed n o r m a l amounts o f B l i n t h e s p l e e n a n d m u s c l e , s l i g h t l y more i n t h e h e a r t k i d n e y and l i v e r .  and a d e f i n i t e r e d u c t i o n , i n t h e  B o t h g r o u p s e l i m i n a t e d t h e same amount  of B l . d.  Metabolism Scrutinio  (38) ha.s r e p o r t e d t h a t v i t a m i n B l ,  e s p e c i a l l y when i n j e c t e d i n t r a v e n o u s l y , w i l l d e c r e a s e t h e b a s a l m e t a b o l i c r a t e a n d i n c r e a s e t h e body w e i g h t o f  10. ( 2 6 ) has l i k e w i s e  hyperthyroid  patients. J o l l i f e  an i n c r e a s e d  r e q u i r e m e n t f o r B l when t h e r e i s g r e a t l y  augmented m e t a b o l i s m s u c h as o c c u r s i n On t h e o t h e r , h a n d , F r a z i e r had  reported  hyperthyroidism.  a n d R a v d i n (o-o) f o u n d t h a t B l  no . e f f e c t on t h e B.M.R. o f t h y r o t o x i c p a t i e n t s ,  a l t h o u g h t h e p a t i e n t s were o b s e r v e d t o g a i n  weight.  Tolerance t o the B Vitamins K l a u s and C l a r k  (?/) report that  the prolonged  a d m i n i s t r a t i o n o f l a r g e amounts o f i n d i v i d u a l v i t a m i n s o f t h e B g r o u p t o r a t s , s u b s i s t i n g on d i e t s e i t h e r e n t i r e l y f r e e f r o m o r p a r t l y d e f i c i e n t ' i n one o r more f a c t o r s o f t h e B complex, f a i l e d t o aggravate m a n i f e s t a t i o n s d e f i c i e n c y . Regarding the tolerance  of t h e  of r a t s t o l a r g e  doses  o f t h e B v i t a m i n s , Kuhn (2>?) s t a t e s t h a t t h e a d m i n i s t r a t i o n o f one t h o u s a n d t i m e s t h e p h y s i o l o g i c a l r e q u i r e m e n t o f B2 d i d n o t c a u s e i n j u r y . Demole ( 2 - ^ ) a l s o o b s e r v e d t h a t  rats  d i d n o t s u f f e r i n j u r y f r o m d o s e s as l a r g e a s . f i v e t h o u s a n d times the p r o t e c t i v e l e v e l of the B Vitamin  vitamins.  B l h a s b e e n g i v e n t o n o r m a l humans i n  d o s e s o f ;S00 mg. ( 150,000 I.U.) d a l l y - w i t h o u t any u n t o w a r d effects  ). S t e i n b e r g  (^z-) r e p o r t s t o x i c a c t i o n i n l e s s  t h a n one p e r c e n t of. h i s c a s e s t r e a t e d w i t h m a s s i v e d o s e s of B l . Sydenstricker,Geeslin,Templeton report that r i b o f l a v i n administered  a n d Weaver {*/<f )  i n d a i l y doses as h i g h  as 3 mg. i n t r a m u s c u l a r l y , 25 mg. i n t r a v e n o u s l y , 50 mg. s u b c u t a n e o u s l y and 60 mg. o r a l l y p r o d u c e d no i l l e f f e c t s on humans. O r a l a n d i n t r a v e n o u s d o s e s o f 100 t o 200 mg. o f p y r i d o x i n e were f o u n d b y W e i g a n d , E c k l e r a n d Chen (5"'/-) t o p r o d u c e no u n t o w a r d was  symptoms i n humans, a l t h o u g h p a i n  r e p o r t e d i n some c a s e s a f t e r i n t r a m u s c u l a r  injections.  F a c t o r s Governing the B a s a l Metabolic. Rate . a. F a s t i n g I n g e n e r a l m o s t w o r k e r s have f o l l o w e d t h e v  rule  t h a t t h e metabolism- i s b a s a l i n a l b i n o r a t s , a f t e r e i g h t e e n h o u r s f a s t i n g . B e n e d i c t and M a c L e o d . ( ^ ) f o u n d t h a t t h e B.M.R. o f t h e f a s t i n g r a t d r o p p e d f r o m c e s s a t i o n o f f e e d i n g to  t h e I 7 t h h o u r p o s t - a b s o r p t i o n and t h e r e a f t e r  remained  e s s e n t i a l l y c o n s t a n t t o t h e 6 4 t h hour p o s t - a b s o r p t i o n . With r a t s f o u r a n d o n e - h a l f months i n age, B e n e d i c t and MacLeod o b t a i n e d a d e c r e a s e ' o f a p p r o x i m a t e l y 10$ i n t h e  first  t w e n t y f o u r h o u r s a f t e r f e e d i n g . Wesson (5"?-) f o u n d t h a t • the  B.M.R. o f t h e f a s t i n g r a t i n c r e a s e s f r o m t h e 1 4 t h t o t h e  2 4 t h hour p o s t - a b s o r p t i o n and s u b s e q u e n t l y d r o p s , r e a c h i n g a l e v e l a t t h e 32nd h o u r . K i n g d o n , B u n n e l a n d G r i f f i t h s i p o ) found t h a t the maximal heat p r o d u c t i o n o c c u r r e d d u r i n g t h e f i r s t hour a f t e r f e e d i n g stopped. Making h o u r l y d e t e r m i n a t i o n s from the f i r s t  hour a f t e r f e e d i n g , they observed  that the metabolic rate d e c l i n e d during the f i r s t  twenty  h o u r s a n d t h e n showed a s h a r p r i s e t o t h e 2 4 t h h o u r ,  12. f o l l o w e d by a d r o p t o t h e 3 6 t h h o u r p o s t - a b s o r p t i o n , b. E n v i r o n m e n t a l  Temperature  B e n e d i c t and MacLeod {if ) made d e t e r m i n a t i o n s o v e r a t e m p e r a t u r e r a n g e o f f r o m 10 C t o 32 G o f t h e b a s a l m e t a b o l i c r a t e s o f a l b i n o r a t s . They r e p o r t e d t h a t b a s a l m e t a b o l i s m was  the  l o w e r e d as t h e t e m p e r a t u r e I n c r e a s e d  up t o 28 C. Above t h i s t e m p e r a t u r e , t h e y f o u n d  thattthe-  b a s a i r - m e t a b o l i s m became c o n s t a n t . S w i f t and F o r b e s ( f ? ) t e s t e d r a t s by s u b m e r g i n g  them,in f o u r - l i t e r j a r s  filled  w i t h a i r , I n w a t e r b a t h s a t v a r i o u s t e m p e r a t u r e s . The o f t e m p e r a t u r e on t h e B.M.R. was o f f r o m 7.5  s t u d i e d over a  G t o 35 G. T h e y r e p o r t e d t h a t t h e  t e m p e r a t u r e was  effect  range  critical  somewhat h i g h e r ( 30 C) t h a n B e n e d i c t and  MacLeod h a d f o u n d . H e r r i n g t o n (5-3) s t a t e d t h a t t h e r m a l n e u t r a l i t y f o r t h e a l b i n o r a t o c c u r s b e t w e e n 28 C and 29 c. T i m e . o f  Day  Horst,Mendel,and  Benedict ( 2 f )  reported that the  b a s a l m e t a b o l i s m of t h e r a t i s s u b j e c t t o d i u r n a l The  C.  o x y g e n c o n s u m p t i o n was  variation.  f o u n d t o be h i g h i n t h e  morning  a n d . l a t e a f t e r n o o n but low a t midday. U s i n g f o u r - r a t s ,  they  f o u n d t h a t t h e v a l u e s o b t a i n e d i n t h e e a r l y m o r n i n g and  late  a f t e r n o o n w e r e f r o m 13 t o 50$ g r e a t e r d u r i n g t h e s e p e r i o d s t h a n a t m i d d a y . On t h e b a s i s o f t h e s e r e s u l t s ,  they  recommended t h a t b a s a l m e t a b o l i s m . m e a s u r e m e n t s s h o u l d be c o n f i n e d t o t h e p e r i o d b e t w e e n 10 A.M.  and 4 P.M.,  d u r i n g t h i s p e r i o d , h e a t p r o d u c t i o n i s more b a s a l .  since  13. d. Age D a v i s ( 10 ) a n d D a v i s a n d H a s t i n g s  (// ) f o u n d  the oxygen consumption p e r k i l o g r a m weight o f r a t s rapidly during the f i r s t  f o u r months a n d more  that  falls  slowly  t h e r e a f t e r . G u l i c k (>/ ) r e p o r t e d t h a t t h e B.M.R. i n c r e a s e s during the f i r s t  f i v e weeks a f t e r " b i r t h , r e a c h e s t h e  maximum i n t h e s i x t h week a n d s u b s e q u e n t l y f a l l s t o approach normal. Kestner the higher metabolic  (2.7 ) a n d B l a n k ( 5" ) b e l i e v e d  that  r a t e per u n i t weight observed i n  s m a l l a n i m a l s c a n n o t be a s c r i b e d t o t h e r e l a t i v e l y  larger  surface area,but rather t o the p r o p o r t i o n of a c t i v e metabolic  tissue.  e. B a r o m e t r i c  Pressure  Wesson ( 5 V ) h a s r e p o r t e d the b a s a l metabolic pressure gas  r a t e due t o c h a n g e s i n t h e  h a v e no a p p r e c i a b l e  Thyroid  determinations.  Preparations  barometric  e f f e c t on t h e r e s p i r a t o r y  exchange and c a n , t h e r e f o r e , b e  metabolic  that the v a r i a t i o n si n  e l i m i n a t e d from b a s a l /  a n d Manner o f A d m i n i s t r a t i o n  B a r n e s a n d Bueno ( 7- ) f o u n d t h a t t h e B.M.R. i n c r e a s e d f r o m 3 0 % t o 4 0 % i n dogs f o l l o w i n g t h e i n j e c t i o n of t h e p i t u i t a r y t h y r e o t r o p h i c hormone. T h i s  e f f e c t was  a t t r i b u t e d t o s t i m u l a t i o n of the t h y r o i d gland  since  t h y r o i d e c t o r a l z e d dogs showed no r e s p o n s e . The d a i l y a d m i n i s t r a t i o n o f d e s i c c a t e d t h y r o i d , c o n t a i n i n g a n amount of i o d i n e equivalent  t o a l l the i o d i n e i n the gland,  14. f a i l e d t o r a i s e the  B.M.R. a s much as t h e  thyreotrophic  hormone. I t was s u g g e s t e d t h a t t h y r o g l o b u l i n , s e c r e t e d b y t h e g l a n d , i s much more e f f e c t i v e t h a n a d m i n i s t e r e d products.  Accordingly,  thyroid  a s t u d y was made t o compare t h e  r i s e i n t h e B'.M.R. due t o t h y r o i d p r e p a r a t i o n s ,  given  s u b c u t a n e o u s l y a n d o r a l l y . F i v e d o g s were t r e a t e d a n d reacted  i n the  same way.  The s u b c u t a n e o u s i n j e c t i o n s p r o v e d  f o u r .to f i v e t i m e s more e f f e c t i v e t h a n t h e o r a l l y ered  t h y r o i d . T h i s i n d i c a t e d t h a t t h e t h y r o i d hormone,  s i m i l a r t o o t h e r hormones, l o s e s c o n s i d e r a b l e the  administ-  alimentary  activity i n  c a n a l . S a l t e r (3d?) r e p o r t e d t h a t t h e hormone  i s decomposed i n - t h e g a s t r o - i n t e s t i n a l t r a c t , b e i n g 62%  as potent a d m i n i s t e r e d  only  o r a l l y as i n t r a v e n o u s l y .  Cooper ( y ) found t h a t t h e o r a l  administration  of s i n g l e doses o f o n e - t e n t h , o n e - f i f t h and o n e - h a l f  grain  desiccated t h y r o i d t o the white r a t , p r e v i o u s l y f a s t e d twenty-four  h o u r s , r e s u l t e d i n a marked r e d u c t i o n i n t h e  B.M.R. f o r s e v e r a l h o u r s f o l l o w i n g t h e a d m i n i s t r a t i o n o f the drug. This  r e d u c t i o n became l e s s m a r k e d a s t h e t h y r o i d  dose i n c r e a s e d  i n potency.  Kunde (33) f o u n d t h a t no s i g n i f i c a n t i n t h e B.M.R. o c c u r r e d  f o r seven t o twelve  s i n g l e dose o f K e n d a l l ' s  change  hours a f t e r a  t h y r o x i n was a d m i n i s t e r e d  intra-  v e n o u s l y o r d e s i c c a t e d t h y r o i d , o r a l l y , t o d o g s . He o b s e r v e d an a p p r e c i a b l e day  Increase  i n the heat production  on t h e  f o l l o w i n g t h e a d m i n i s t r a t i o n o f t h e hormone. He a l s o  15. found that a f t e r repeated d a i l y doses of e i t h e r t h y r o i d or thyroxine, the basal metabolic reaching  rate progressively  increased,  a maximum i n t h r e e weeks. He s t a t e d t h a t a  q u a n t i t a t i v e r e l a t i o n s h i p between t h e t h y r o i d i n g e s t e d t h e B.M.R. d o e s n o t e x i s t .  and  16.  EXPERIMENTAL Animals T h i r t y a l b i n o r a t s , male and f e m a l e , were u s e d i n t h i s i n v e s t i g a t i o n , a l l r a t s b e i n g the P I progeny of f o u r animals obtained from the Winstar I n s t i t u t e , P h i l a d e l p h i a . Environment  ,•  The  r a t s were h o u s e d  i n a room m e a s u r i n g  a p p r o x i m a t e l y 8 f t . by 6 f t . by 6 f t . The t e m p e r a t u r e o f t h e room was  t h e r m o s t a t i c a l l y c o n t r o l l e d a t 76 F,and t h e  r e l a t i v e ^ h u m i d i t y , was drafts  45 t o 50%. The room was  f r e e from  and v e n t i l a t e d b y d r a w i n g i n f r e s h a i r f r o m t h e  o u t s i d e . Two  60 w a t t b u l b s p r o v i d e d i l l u m i n a t i o n , a u t o -  m a t i c a l l y c o n t r o l l e d by a t i m e c l o c k t o g i v e t e n h o u r s light  p e r day. The r a t cages w e r e c o n s t r u c t e d o f g a l v a n i z e d  m e t a l , e a c h w i t h s o l i d ' s i d e s and b a c k , and a w i r e t o p , b o t t o m and f r o n t . E a c h c a g e was pan f i l l e d w i t h f i n e sawdust  equipped w i t h a dropping  t o a b s o r b m o i s t u r e and t o  f a c i l i t a t e c l e a n i n g . The c a g e s were c l e a n e d e a c h week and then sprayed w i t h  lysol.  W a t e r was  s u p p l i e d from erlenmeyer  flasks,inverted  and f a s t e n e d i n f r o n t o f t h e c a g e , w i t h a b e n t g l a s s p r o j e c t i n g i n t o t h e cage t o s e r v e as an o u t l e t The r a t s were q u a r t e r e d two  tube  tube.  or three to  a.cage.  17. F o r t h e w o r k on v i t a m i n s , i t was f o u n d e x p e d i e n t t o i s o l a t e t h e a n i m a l s , p l a c i n g them one t o a c a g e . Diet T h r o u g h o u t t h e i n v e s t i g a t i o n t h e r a t s were g i v e n w a t e r a d l i b i t u m . The r a t s w e r e f e d once e a c h d a y , a d a i l y , r a t i o n , p e r r a t , c o n s i s t i n g o f f r o m two t o t h r e e  checkers  o f s p e c i a l l y p r e p a r e d f o o d . T h e s e c h e c k e r s were s u p p l i e d by t h e P u r i n a M i l l s , S t . L o u i s , M o . , u n d e r t h e t r a d e name o f " P u r i n a F o x Chow", a n d were s t a t e d t o c o n t a i n : f l a v i n concentrate carotene wheat germ d r i e d skim m i l k l i v e r meal brewer's d r i e d y e a s t b a r l e y malt f i s h meal d r i e d meat  a l f a l f a meal corn g r i t s soybean meal molasses d r i e d beet pulp , cod l i v e r o i l 1% s t e a m e d bone m e a l 1% i o d i z e d s a l t ,  Compared t o t h e known n u t r i t i o n a l  requirements  o f t h e l a b o r a t o r y r a t , an a n a l y s i s o f t h e P u r i n a c h e c k e r s by t h e P u r i n a L a b o r a t o r i e s showed t h a t a p p r o x i m a t e l y two times t h e v i t a m i n requirements Source  are present.  of Thyroxine and Vitamins The  1. O n e - t e n t h Burroughs  f o l l o w i n g drugs were used: g r a i n d e s i c c a t e d t h y r o i d , t h e product of  W e l l c o m e & Co.  Each t a b l e t i s s t a t e d t o  represent one-tenth grain(,0065gm.) of f r e s h h e a l t h y gland substance, equivalent t o l / 3 3 r d g r a i n t h y r o i d  ?  i o d i n e c o n t e n t i s 0.1$. 2. O n e - t e n t h  g r a i n d e s i c c a t e d t h y r o i d , t h e product of  The  18. P a r k e , D a v i s & Co. E a c h t a b l e t r e p r e s e n t s o n e - t e n t h t h y r o i d , c o n t a i n i n g 0.3% 3. O n e - q u a r t e r  grain  iodine.  grain desiccated thyroid(Burroughs  & Co.). Each t a b l e t r e p r e s e n t s one-quarter  Wellcome  grain(l6  mgm.)  of f r e s h h e a l t h y g l a n d s u b s t a n c e , e q u i v a l e n t t o 8/40ths dry thyroid,B.P.  The i o d i n e c o n t e n t i s 0.25% .  4. V i t a m i n B l ( t h i a m i n e h y d r o c h l o r i d e ) . E a c h d o s e c o n s i s t e d o f 1 mg.,  e q u i v a l e n t t o 333 i n t e r n a t i o n a l  o r 333 U.S.P. u n i t s . P r o d u c t Ltd.  o f t h e B r i t i s h Drug  units  Houses,  (B.D.H.).  5. V i t a m i n B2 ( r i b o f l a v i n  ). Each dose c o n s i s t e d o f 1  e q u i v a l e n t t o 400 S h e r m a n - B o u r q u i n u n i t s . A p r o d u c t  mg.,  of the  B r i t i s h D r u g H o u s e s , L t d . (B..D.H.). 6. V i t a m i n B6 ( p y r i d o x i n e h y d r o c h l o r i d e ). E a c h d o s e c o n s i s t e d o f 1 mg.  o r 1000 m i c r o g r a m s ( g a m m a s ) .  No  commonly  a c c e p t e d b i o l o g i c u n i t i s g i v e n . The p r o d u c t o f E l i L i l l y  &  Co., and s o l d c o m m e r c i a l l y a s H e x a b e t a l i n . The above d r u g s w e r e a d m i n i s t e r e d w i t h t h e f o o d . A n o r m a l d a i l y r a t i o n o f t h e c h e c k e r s ( a p p r o x i m a t e l y 18 was p u l v e r i z e d i n a m o r t a r , a d m i x e d as h o m o g e n e o u s l y p o s s i b l e v/ith t h e d r u g u s e d , and reformed  into a  gms.  as  checker  by a d d i n g a l i t t l e w a t e r , and a l l o w i n g t h e p a s t y m i x t u r e t o d r y . S i n c e r i b o f l a v i n i s p h o t o l i t h i c , c a r e was t a k e n t o prevent i t s decomposition  by t h e l i g h t . A l l d i e t s  c o n t a i n e d t h e d r u g s were p r e p a r e d i m m e d i a t e l y feeding time.  which  before  19. Apparatus a. M o d i f i c a t i o n s f r o m t h e O r i g i n a l D e s i g n The a p p a r a t u s u s e d was .designed and F . R . G r i f f i t h , J r .  b y E.L.Schwabe  (itf ) , a t t h e U n i v e r s i t y o f B u f f a l o , t o  d e t e r m i n e "basal m e t a b o l i s m b y t h e method o f i n d i r e c t calorimetry. C e r t a i n m o d i f i c a t i o n s vrere made i n t h e a p p a r a t u s by W.Cooper ( V ) / a t t h e U n i v e r s i t y o f B r i t i s h  Columbia,  i n t h e 'manner o f r e m o v i n g t h e c a r b o n d i o x i d e a n d o f r e g i s t e r i n g t h e oxygen consumption. I n s t e a d o f u s i n g a standardized  s o l u t i o n of barium hydroxide  and b r i n g i n g t h e  chamber a i r ' . i n c o n t a c t w i t h t h i s , t o e f f e c t t h e r e m o v a l o f c a r b o n d i o x i d e C o o p e r e m p l o y e d s o d a l i m e . The a n i m a l chamber c o n s i s t e d o f two p a r t s , a n a b s o r p t i o n u n i t containing-the approximately  soda l i m e , a n d a w i d e g l a s s v e s s e l , 9-|- i n c h e s  i n diameter,  which f i t t e d over the  a b s o r p t i o n u n i t . This u n i t c o n s i s t e d of a round d i s c , 8f- i n c h e s  wooden  i n diamet-er a n d -J- i i t c h e s t h i c k . T h e soda  l i m e was p l a c e d b e t w e e n w a l l s o f c o p p e r g a u z e , c o n c e n t r i c a l l y p l a c e d around t h e o u t s i d e o f t h e c i r c u l a r o f wood a n d f i r m l y c e m e n t e d t o i t .  piece  The w a l l s were 2-jr i n c h e s  h i g h and § i n c h e s a p a r t . The a b s o r p t i o n u n i t h e l d approximately  400 grams o f soda l i m e .  The b a s e o f t h e chamber was a t h i n c o p p e r p l a t e i n w h i c h was i m p r e s s e d a c i r c u l a r t r o u g h t o f i t t h e r i m o f the. g l a s s v e s s e l . When i n u s e , t h i s t r o u g h was p a r t l y  20. f i l l e d w i t h mercury, thus  e n s u r i n g an a i r - t i g h t s e a l f o r  t h e a n i m a l chamber. An i n l e t t u b e f r o m t h e p e n e t r a t e d t h i s c o p p e r p l a t e and p a s s e d chamber t h r o u g h  i n t o the  animal  a h o l e b o r e d i n . t h e wooden b a s e o f ' t h e  absorption unit. The  apparatus  .  s o d a l i m e was  found  to give  satisfactory  r e s u l t s f o r about f i f t y twenty-minute runs, a f t e r which i t s - e f f i c i e n c y c o u l d n o t be r e l i e d u p o n . The  second m o d i f i c a t i o n c o n s i s t e d i n  substituting  a h e a v i e r f l o a t i n t h e w a t e r manometer i n p l a c e o f t h e l i g h t p a r a f f i n e d c o r k Yfhich was  used to support  t h e bamboo r o d  and w r i t i n g p o i n t . C o o p e r f o u n d t h a t s l i g h t i n the apparatus fluctuations  vibrations  were t r a n s m i t t e d t o the c o r k f l o a t c a u s i n g  I n the graph.  R e p l a c i n g t h i s l i g h t f l o a t by  heavier glass f l o a t reduced  a  t h e s e n s i t i v i t y and e l i m i n a t e d  t h e f l u c t u a t i o n s , r e c o r d i n g t h e r i s e i n t h e manometer l e v e l w i t h t h e same f i d e l i t y b u t w i t h a smmother c u r v e . In t h e o r i g i n a l d e s i g n , the animal . p l a c e d above t h e a n i m a l ' s t h e chamber was  chamber  was  oxygen s u p p l y . S i n c e the a i r i n  made t o c i r c u l a t e i n o r d e r t o e x p e d i t e  removal of carbon  the  d i o x i d e and i t s a b s o r p t i o n b y t h e b a r i u m  h y d r o x i d e , some d e v i c e was  found  necessary-to  d i f f u s i o n of the carbon d i o x i d e back i n t o the F o r t h i s r e a s o n a M u l l e r v a l v e was l i n e connecting the apparatus  prevent  the  apparatus.  i n s t a l l e d on t h e i n t a k e  w i t h the animal  chamber..  However, s i n c e t h e a b s o r p t i o n u n i t , as m o d i f i e d b y  Cooper,  21. was  contained, w i t h i n the animal  animal  chamber, and  since  the  chamber i t s e l f c o u l d be c o n v e n i e n t l y p l a c e d a t some  d i s t a n c e b e l o w t h e oxygen s u p p l y i n t h e a p p a r a t u s , M i i l l e r v a l v e was,  f o r a l l p r a c t i c a l p u r p o s e s , deemed  unessential.. Slight pressure  changes r e g i s t e r e d by  o i l manometers p l a c e d on t h e two i n d i c a t e d t h a t some s u c t i o n was  r e q u i r e d t o draw t h e  w o u l d r e s u l t f r o m t h i s f o r c i b l e s u c t i o n , and no  longer expedient  i t was. removed f r o m t h e  the  s i d e s of t h e M u l l e r v a l v e  oxygen t h r o u g h t h i s v a l v e . S i n c e a s l i g h t s o u r c e  v a l v e was  the  f o r i t s primary  of e r r o r  since  the  function,  apparatus.  A d i a g r a m of t h e a p p a r a t u s i s ; p r e s e n t e d on page 22.  For  a d e t a i l e d d e s c r i p t i o n of the apparatus,  i s g i v e n t o t h e p u b l i s h e d r e p o r t o f Schwabe and and  to the..reports of K i l b a n k  izl)  and  Cooper ( 7  reference  Griffith ).  (3.7)  23. b. O p e r a t i o n o f t h e  Apparatus  A f t e r t h e r a t i s p l a c e d i n t h e chamber, and  the  g l a s s t o p o f t h e a n i m a l chamber i s p r e s s e d f i r m l y down i n the mercury  t r o u g h t o ensure an a i r - t i g h t  apparatus i s ' f l u s h e d w i t h oxygen, from a commercial  seal,  the  s u p p l i e d to the  apparatus  c y l i n d e r o f t h e gas. As t h e a n i m a l  r e s p i r e s , and c a r b o n d i o x i d e and m o i s t u r e a r e a b s o r b e d t h e .soda l i m e , o x y g e n d i f f u s e s i n t o t h e chamber f r o m  by the  e r l e n m e y e r f l a s k (G - r e f e r t o d i a g r a m , p . 2 2 ) t o m a i n t a i n a u n i f o r m i n t e r n a l g a s e o u s p r e s s u r e . The  gaseous p r e s s u r e  w i t h i n t h e e r l e n m e y e r f l a s k and t h e a n i m a l chamber i s k e p t a t a t m o s p h e r i c p r e s s u r e by a l l o w i n g w a t e r t o s i p h o n i n f r o m c y l i n d e r D as o x y g e n i s drawn out f r o m  flask(G).Cylinde  ( D ) i s c o n n e c t e d t o t h e manometer s y s t e m ( J ) c o n t a i n i n g t h e glass f l o a t  (K) and w r i t i n g , p o i n t ( L ) . The  gaseous p r e s s u r e  i n t h e t u b e c o n n e c t i n g c y l i n d e r (D) t o t h e manometer  system  i s l e s s t h a n a t m o s p h e r i c . Thus t h e w a t e r l e v e l i n t h e open arm o f t h e w a t e r manometer i s l o w e r t h a n t h a t i n t h e e n c l o s e d arm.  As w a t e r s i p h o n s o v e r f r o m c y l i n d e r D t o  f l a s k G, oxygen b u b b l e s i n t o D f r o m t h e r u b b e r b l a d d e r ( C) t h r o u g h tube x. C o n s e q u e n t l y  t h e g a s e o u s p r e s s u r e above t h e  e n c l o s e d arm o f t h e w a t e r manometer g r a d u a l l y r e t u r n s t o a t m o s p h e r i c as t h e w a t e r l e v e l i n D i s l o w e r e d . i n c r e a s i n g p r e s s u r e i n t h e e n c l o s e d arm  With  o f t h e manometer,  t h e w a t e r l e v e l i n t h e open arm r i s e s , c a u s i n g t h e kymograph n e e d l e  ( L ) t o r i s e . Thus t h e oxygen consumed by  24. t h e r a t c a n be computed f r o m t h e v e r t i c a l r i s e o f t h e kymograph  needle. When a r u n i s s t a r t e d , t h e kymograph drum i s  so p l a c e d t h a t t h e w r i t i n g - p o i n t r e s t s d e l i c a t e l y  against  t h e smoked g r a p h p a p e r . The drum i s t h e n spun s o t h a t a b a s e l i n e i s t r a c e d a g a i n s t t h e graph from which the v e r t i c a l r i s e o f t h e n e e d l e c a n be meastired. attached thirty  The drum i s  t o a c l o c k g e a r e d t o make one r e v o l u t i o n i n  minutes. At t h e con-clusion o f t h e run,  t h e graph paper  i s dipped i n v a r n i s h , mixed w i t h t u r p e n t i n e , t o preserve it  and t h e n s u s p e n d e d o v e r a t r o u g h u n t i l d r y . The  briefly,  procedure f o r manipulating  the valves i s ,  as f o l l o w s :  a. To o p e r a t e a p p a r a t u s ( a s s u m i n g a l l v a l v e s t o be closed) 1. a f t e r t h e a n i m a l h a s been p l a c e d i n t h e chamber, as d e s c r i b e d , Valve  open v a l v e s 12,8,9,10 and 1 1 .  9 n e e d n e v e r be c l o s e d . 2. when C i s p a r t l y i n f l a t e d ,  c l o s e 12.  3. d e f l a t e C g e n t l y t o f l u s h G and P. 4. c l o s e v a l v e s 11,8 and 10( when t h e o i l manometer r e g i s t e r s e q u a l  i n t e r n a l and e x t e r n a l  5. r e s t t h e w r i t i n g p o i n t d e l i c a t e l y  pressure. against  t h e g r a p h p a p e r a n d s p i n t h e drum t o o b t a i n a b a s e l i n e . 6. open v a l v e s 7,1 a n d 5. The a p p a r a t u s i s now in  operation.  213 & b. To d i s c o n t i n u e t h e r u n , 1. c l o s e v a l v e s 1,7 and 5. 2. open v a l v e s 8 and 11 3. t h e a n i m a l may now be removed f r o m t h e chamber c. To r e s e t t h e  apparatus,  1. c l o s e a l l v a l v e s , w i t h t h e e x c e p t i o n o f 9 and 2. open v a l v e s 2,3 and 6. 3. when t h e w a t e r i n c y l i n d e r D h a s r e t u r n e d t o level  z, c l o s e v a l v e s 2,3 and 6. d. To r e s e t the- l e v e l l i n g 1. r e f i l l  bulbs,  l e v e l l i n g bulb.B by e l e v a t i n g b u l b A  a b o v e B a n d o p e n i n g v a l v e s 3 and 4. 2. s h u t v a l v e s 3 and 4 and r e t u r n b u l b A t o i t s former p o s i t i o n . Measurement  of t h e B a s a l Metabolic  Rate  Newton's Law t h a t t h e r a t e o f c o o l i n g o f a body depended on I t s s i z e s u g g e s t e d  t o Bergman (1847) t h a t a  r e l a t i o n s h i p e x i s t e d between t h e s u r f a c e a r e a o f an and  animal  I t s h e a t p r o d u c t i o n . T h i s i s t h e b a s i s f o r most  formulae  used I n computing the b a s a l metabolic The b a s a l m e t a b o l i c  ratio  of the caloric  rates  r a t e may be e x p r e s s e d  today. as t h e  v a l u e o f t h e oxygen consumed i n a  given time, t o the'surface area of the animal. Benedict  (3 ) s t a t e d t h a t i t may be  assumed  t h a t the r e s p i r a t o r y q u o t i e n t o f a r a t w h i c h has been twenty f o u r hours without  f o o d i s c l o s e t o .72 .  On t h i s a s s u m p t i o n  h e h a s shown t h a t l i t t l e  i n t r o d u c e d i f oxygen alone i s determined  error i s  and t h e  heat  p r o d u c t i o n c a l c u l a t e d from t h i s . A c c o r d i n g t o Lusk ( 3 4 ) t h e c a l o r i c v a l u e o f one l i t e r o f o x y g e n a t S.T.P. when t h e R.Q.. i s .72 i s 4.702 c a l o r i e s . Tp o b t a i n t h e  caloric  v a l u e o f t h e o x y g e n consumed, t h e volume o f o x y g e n consumed i n t e n m i n u t e s ( o b t a i n e d f r o m g r a p h ) i s c o n v e r t e d t o one h o u r and c o r r e c t e d f o r t e m p e r a t u r e .  The c o r r e c t e d volume  i n l i t r e s , m u l t i p l i e d b y 4.702 g i v e s t h e c a l o r i c v a l u e o f t h e o x y g e n consumed i n one h o u r . A number o f f o r m u l a e surface area o f the r a t . A l i s t  e x i s t f o r e s t i m a t i n g the o f t h e s e f o r m u l a e has been  g i v e n b y C o o p e r ( 7 ). S i n c e t h e d i f f e r e n t f o r m u l a e little  show  a g r e e m e n t i n t h e B.M.R. v a l u e s o b t a i n e d , a n d s i n c e  i t was d e s i r e d t o c o r r e l a t e c e r t a i n B.M.R. v a l u e s w i t h r e s u l t s o b t a i n e d b y C o o p e r , t h e f o r m u l a -adopted h e r e i s .  .  .  .  .  .  .  ...  .  .  t h a t o f R u b n e r , i . e . , t h e S u r f a c e A r e a e q u a l s 9.1 x W e i g h t The  surface area obtained by t h i s formula i s divided by  10,000 t o c o n v e r t i t t o s q u a r e m e t e r s .  Thus t h e v a l u e f o r  the b a s a l metabolic r a t e i s expressed as c a l o r i e s p e r square meter per hour.  fig.  2.  A sample c a l c u l a t i o n  follows.  Diagrammatic r e p r e s e n t a t i o n o f a graph  2  /  To i n t e r p r e t t h e g r a p h , r e p r e s e n t e d b y f i g . 2 on t h e f o r e g o i n g p a g e , i t i s r e q u i r e d t o know t h e h o r i z o n t a l d i s t a n c e t r a v e r s e d i n a u n i t t i m e , and a l s o t o know the oxygen consumption r e p r e s e n t e d by the v e r t i c a l  rise  a b o v e t h e b a s e l i n e . T h i s c a l i b r a t e d d a t a was f o u n d t o b e : 1 cm. r i s e  -  1 cm. h o r i z o n t a l -  23.47 c c s . o f o x y g e n .625 m i n u t e s  She oxygen consumption f o r a t e n minute p e r i o d was f o u n d b y m e a s u r i n g a l o n g t h e b a s e l i n e a d i s t a n c e o f 16 cm.- f r o m t h e p o i n t , a t w h i c h i t i s i n t e r s e c t e d b y t h e graph. The v e r t i c a l h e i g h t from t h i s p o i n t t o ;  the.graph,  i s . t h e n measured. T h i s v e r t i c a l d i s t a n c e m u l t i p l i e d by t h e v o l u m e t r i c e q u i v a l e n t o f t h e manometer (23.47 c c s . ) g i v e s t h e oxygen consumption f o r a t e n minute r u n . I f t h e graph, i s n o t s t r a i g h t , t h e n ' a b a s a l p o r t i o n o f t h e c u r v e s h o u l d be s e l e c t e d , i . e . where t h e c u r v e shows t h e l e a s t inclination  t o the b a s e l i n e . Using p a r a l l e l  rulers,  the  b a s e l i n e may t h e n be moved u p o r down as t h e o c c a s i o n demands. L e t u s assume t h e v e r t i c a l r i s e i s 1.75 a n d the weight  o f t h e r a t i s 170( r a t £ 1 0 0 , tablefcfe).  temperature  i s 28° C.  The b a s a l m e t a b o l i c follows:  The  r a t e i s c a l c u l a t e d as  28. 25.47 x ,1.75 x 60 x 273 x 4.702 x 1000 ~ 27T-T —  MulK V»l. in  consumed Converted (O  minutes  to  Corrected  hours  Caloric  f o r Tump- o f of-  i  by value liter  Oxy^<tn  =37.3 cals/m^hr T/3 9.1 x W 10,000 ' Divided by tht •sor-poce. a<r-ea -  of  r«e  v  Methods E m p l o y e d  a. F a c t o r s I n f l u e n c i n g t h e B.M.R, 1. L e n g t h o f f a s t i n g P o u r r a t s ( t h e number e m p l o y e d b y E i n g d o n , Bunnel and G r i f f i t h first  ) , two o f each s e x , w e r e u s e d i n t h e  e x p e r i m e n t , w h i c h was 'commenced a t 9 A.M. a n d  c o n c l u d e d a t 3 P.M. t h e f o l l o w i n g d a y , c o n t i n u o u s d e t e r m i n a t i o n s o f t h e B.M.R. b e i n g made a t i n t e r v a l s o f six  h o u r s . The r a t s were f e d p r i o r t o t h e e x p e r i m e n t , t h e  f o o d b e i n g r e m o v e d a t 9 A.M. B e t w e e n d e t e r m i n a t i o n s o f t h e B.M.R., t h e r a t s w e r e p r o v i d e d w i t h w a t e r a n d p e r m i t t e d normal a c t i v i t y . the  The e n v i r o n m e n t a l t e m p e r a t u r e  throughout  e x p e r i m e n t was b e t w e e n 25 C a n d 3 1 G. A t t h i s  e r a t u r e , however, l i t t l e  temp-  a c t i v i t y was d i s p l a y e d . P r i o r t o  e a c h r u n t h e a n i m a l was .weighed. ( c f . T a b l e l a , g r a p h i c ) Prom t h e r e s u l t s o b t a i n e d i n t h e f i r s t it felt  experiment,  d e s i r a b l e t o r e p e a t t h e e x p e r i m e n t f r o m t h e 18 t h  29. hour onwards, making h o u r l y d e t e r m i n a t i o n s . Pour males and t h r e e f e m a l e s w e r e f a s t e d f r o m 18 t o 2 1 h o u r s a n d e x p e r i m e n t a l r u n s made e a c h h o u r u p t o 27 h o u r s . The e x p e r i m e n t was  c o n d u c t e d a t 28°G, no t i m e b e i n g a l l o w e d f o r t h e a n i m a l s  to a d j u s t t o the h i g h e r temperature.  ( c f . T a b l e l b , graph!b)  2. E n v i r o n m e n t a l T e m p e r a t u r e S i x a n i m a l s , two m a l e s a n d f o u r f e m a l e s were t e s t e d on f o u r s u c c e s s i v e d a y s , a f t e r f a s t i n g p e r i o d s o f 20 h o u r s , a t t e m p e r a t u r e s o f 21°C, to determine  27°C, 31.5°C a n d 39°C,  t h ee f f e c t o f environmental temperature  on t h e  B.M.R. o f t h e f a s t i n g r a t . By t h i s s t a g e i n t h e w o r k t h e a p p a r a t u s h a d been removed t o a s m a l l g l a s s e d - i n room, measuring  a p p r o x i m a t e l y 5 f t . b y 7 f t . The room was h e a t e d  by a s m a l l h e a t e r c o n t a i n i n g two e l e c t r i c  c o i l s , one o f  w h i c h was u n d e r t h e r m o s t a t i c c o n t r o l . The o t h e r c o i l  served  t o r e d u c e t h e t i m e r e q u i r e d t o b r i n g t h e room t o t h e d e s i r e d t e m p e r a t u r e , a t w h i c h t i m e t h i s c o i l was c u t o u t . B e f o r e t h e a c t u a l d e t e r m i n a t i o n s : w e ' r e made,/the a n i m a l s were p l a c e d i n t h e room f o r a p e r i o d - o f f r o m one t o two h o u r s i n o r d e r t o a d j u s t themselves m e t a b o l i c a l l y t o the change.in t h e e n v i r o n m e n t a l t e m p e r a t u r e . ( c f . T a b l e 2-, g r a p h % ) 3. Age As t h e s u r v e y shows, t h e B.M.R. o f t h e young r a t has b e e n o b s e r v e d t o r i s e s h a r p l y d u r i n g t h e f i r s t  s i x weeks,  p o s t - n a t a l , l e v e l s o f f , and f r o m t h e s e v e n t h week onwards d e c l i n e s t o t h e f o u r t h m o n t h a f t e r w h i c h t h e B.M.R* i n t h e  50. h e a l t h y a n i m a l r e m a i n s more o r l e s s s t a t i o n e r y u p t o two y e a r s . I t was d e s i r e d t o a s c e r t a i n t h e e a r l i e s t age a t w h i c h t h e B.M.R. becomes  c o n s t a n t , so t h a t a v a r i a t i o n f r o m  B.M.R. w o u l d d e n o t e t h e e f f e c t o f some s u p e r i m p o s e d  this  factor  s u c h a s d e s i c c a t e d t h y r o i d a n d n o t t h e e f f e c t o f age and g r o w t h . P o u r r a t s , two m a l e s  a n d two f e m a l e s , w e r e u s e d . The  a n i m a l s w e r e f a s t e d 2 4 h o u r s - p r i o r i?o t h e e x p e r i m e n t s , w h i c h w e r e c a r r i e d o u t a t a t e m p e r a t u r e o f a p p r o x i m a t e l y 28 d e g r e e s C e n t i g r a d e . The d e t e r m i n a t i o n s w e r e made a t i n t e r v a l s o f seven days throughout t h e e x p e r i m e n t a l p e r i o d , b e g i n n i n g a t t h e s i x t h week a n d c o n t i n u i n g t o t h e t w e l f t h week. V a l u e s were a g a i n o b t a i n e d a f t e r seven months. ( c f . T a b l e d  graph.3 )  4. l i m e o f d a y Pour r a t s  ( t h e same number u s e d b y H o r s t , M e n d e l  and B e n e d i c t ) , t h r e e m a l e s  a n d one f e m a l e f r o m t h e same l i t t e r ,  were u s e d t o t e s t t h e d i u r n a l e f f e c t o n t h e b a s a l m e t a b o l i c r a t e . The r a t s w e r e f a s t e d f o r 24 h o u r s a n d d e t e r m i n a t i o n s made a t a t e m p e r a t u r e o f 28°C. D e t e r m i n a t i o n s w e r e made a t , 10 A.M., 12 A.M. a n d 4 P.M. ( c f . T a b l e H , g r a p h H ) b. D e s i c c a t e d T h y r o i d 1. A d m i n i s t e r e d a f t e r  Fasting  Cooper ( 7 ) f o u n d t h a t t h e o r a l  administration  o f g r a d e d s i n g l e d p s e s o f B u r r o u g h s WeTlcome Co. d e s i c c a t e d t h y r o i d g l a n d ( l / l O t h , l / 5 t h and l / 2 g r a i n ) t o t e n r a t s f a s t e d 2 4 h o u r s , p r o d u c e d a m a r k e d r e d u c t i o n i n t h e B.M.R., measured h o u r l y f o r s i x h o u r s a f t e r t h e a d m i n i s t r a t i o n o f  31. the drug.  S i n g l e d e t e r m i n a t i o n s made a t i n t e r v a l s o f 24 h o u r s  t h e r e a f t e r f o r one week f a i l e d t o show a n y i n c r e a s e i n t h e B.M.R. o v e r t h e i n i t i a l b a s a l v a l u e s . The d e p r e s s i o n i n t h e B.M.R. a p p e a r e d most marked f o r t h e l / l O g r a i n d o s e amounting t o a 40% r e d u c t i o n from the i n i t i a l b a s a l value one h o u r a f t e r f e e d i n g t h e t h y r o i d . F o r t h e l / 5 g r a i n d o s e t h i s d e p r e s s i o n w a s ' l e s s m a r k e d and f o r t h e 1/2 g r a i n d o s e only a s l i g h t reduction resulted. These experiments  were r e p e a t e d u s i n g l / l O g r a i n  Burroughs Wellcome d e s i c c a t e d t h y r o i d , a d m i n i s t e r e d  orally  a f t e r an i n i t i a l d e t e r m i n a t i o n o f the b a s a l • m e t a b o l i c r a t e was  made. S i x r a t e w e r e u s e d a n d f a s t e d f o r 24 h o u r s . The  t e s t s Yrere made, h o w e v e r , a t a n e n v i r o n m e n t a l  temperature  o f 28°G , somewhat h i g h e r t h a n t h a t u s e d b y C o o p e r .  Hourly  d e t e r m i n a t i o n s were made f o r f i v e h o u r s . ( c f . T a b l e 5" g r a p h "5 ) ""Two  o t h e r g r o u p s o f a n i m a l s were e a c h f a s t e d  19 h o u r s a n d f e d l / l O g r a i n d e s i c c a t e d t h y r o i d a f t e r t h e p r e l i m i n a r y b a s a l d e t e r m i n a t i o n s h a d b e e n made. H o u r l y d e t e r m i n a t i o n s w e r e made f o r a p e r i o d o f f o u r h o u r s w i t h one  group, c o m p r i s i n g seven a n i m a l s , and f o r seven hours  w i t h t h e s e c o n d g r o u p , composed o f e i g h t r a t s .  ( Table 5 graph5)  2. A d m i n i s t e r e d p r i o r t o F a s t i n g To  t e s t t h e e f f e c t o f a s m a l l s i n g l e dose o f  desiccated thyroid, administered prior t o fasting,  twelve  a n i m a l s w e r e u s e d . T h e s e were d i v i d e d i n t o two g r o u p s , o n e group r e c e i v i n g l / l O t h g r a i n Burroughs Wellcome d e s i c c a t e d  32. t h y r o i d , t h e second g r o u p d r e c e i v i n g l / l O t h g r a i n P a r k e , Dasris d e s i c c a t e d t h y r o i d . A l l a n i m a l s were f a s t e d 24 h o u r s a f t e r w h i c h t h e B.M.R.s were d e t e r m i n e d a t a n e n v i r o n m e n t a l t e m p e r a t u r e o f 29° C. I m m e d i a t e l y a f t e r t h e s e d e t e r m i n a t i o n s , t h e r a t s w e r e s u p p l i e d w i t h n o r m a l r a t i o n s . The B.M.R.s w e r e d e t e r m i n e d once d a i l y , f o l l o w i n g 2 4 h o u r s  fasting,  u n t i l t h e ' b a s a l v a l u e s were f o u n d t o be n o r m a l . A c o m p a r i s o n of the r e l a t i v e potencies^ o f a s i n g l e a d m i n i s t r a t i o n o f t h e s e two d r u g s i n e l e v a t i n g t h e B.M.R. i s shown b y t a b l e s 6 a , Cb-, g r a p h d> . c. V i t a m i n s B l , B2,aB6 a h d a l ^ l O g r a i n  thyroid  I n d e t e r m i n i n g t h e e f f e c t o f a d m i n i s t e r i n g B1,B2 and B6 t o r a t s whose B.M.R.s ,had been e l e v a t e d b y d a i l y ;  doses  o f l / l O g r a i n d e s i c c a t e d t h y r o i d , s i x r a t s were u s e d , f i v e m a l e s and one f e m a l e , a l l l i t t e r mates. These r a t s were f e d a p p r o x i m a t e l y 18 grams o f f o o d d a i l y a n d r e c e i v e d w a t e r a d l i b i t u m . A f a s t i n g p e r i o d o f 20 h o u r s was a l l o w e d b e t w e e n e a c h e x p e r i m e n t a l r u n . The a n i m a l s were b r o u g h t t o t h e e x p e r i m e n t a l rosom ( t e m p e r a t u r e 28°G) a t l e a s t one h o u r b e f o r e a r u n was made and w e i g h e d e a c h d a y j u s t previou-s t o t h e d e t e r m i n a t i o n o f t h e B.M.R.s » The f o l l o w i n g t e s t s were conducted: 1. F o r s e v e n d a y s t h e B.M.R. f o r e a c h r a t was d e t e r m i n e d d a i l y a f t e r a 20 h o u r f a s t . Then e a c h r a t was f e d 18 grams o f f o o d t o g e t h e r w i t h l / l O g r a i n thyroid.  desiccated  33. 2. the of  F o r the" s u c c e e d i n g n i n e d a y s , t h e r a t s  same r a t i o n o f f o o d w i t h  l / l O g r a i n t h y r o i d and 1 mg.  c r y s t a l l i n e thiamine hydrochloride. 3.  received  •  A f t e r a n i n t e r v a l o f f i v e d a y s , d u r i n g xvhich  time t h e rats: received  normal r a t i o n s  and t h e t h y r o i d , h u t  w i t h no s u p p l e m e n t o f t h i a m i n e , t h e t e s t s w e r e resumed supplementing the d i e t with  t h y r o i d and 1 mg. o f r i b o f l a v i n  d a i l y . B a s a l m e t a b o l i c v a l u e s were a g a i n d e t e r m i n e d f o r a n i n e day p e r i o d . 4. A f t e r a n o t h e r f i v e d a y i n t e r v a l d u r i n g w h i c h t h e n o r m a l r a t i o n and t h y r o i d a l o n e ?/as f e d , t h e d i e t was supplemented w i t h  1 mg. o f p y r i d o x i n e  together with the  t h y r o i d . The r e s u l t s a r e shown i n t a b l e s 1 — IT-  d. V i t a m i n s B l B 2 , B 6 and ^ g r a i n ?  r  a n d graph.;,.!  thyroid  Three,.'Ot.herogroups o f r a t s , s i x t o e a c h g r o u p , w e r e u s e d t o d e t e r m i n e t h e e f f e c t s o f t h e v i t a m i n s B1,B2 and  B6, s i n g l y and i n c o m b i n a t i o n , oh t h e b a s a l  r a t e , a f t e r i t had been e l e v a t e d  by the administration  d a i l y amounts o f \ g r a i n B u r r o u g h s W e l l c o m e thyroids as  metabolic  The same e x p e r i m e n t a l c o n d i t i o n s  of  desiccated  were o b s e r v e d  f o r the l / l O grain t h y r o i d , described i n the preceding  s e c t i o n . The f o l l o w i n g 1.  t e s t s w e r e made:  The e f f e c t o f a s i n g l e d o s e o f B u r r o u g h s  W e l l c o m e \ g r a i n t h y r o i d was a s c e r t a i n e d determinations d a i l y f o r a period  by making m e t a b o l i c  of eight  days.  34. 2. :  The  e f f e c t of r e p e a t e d d a i l y doses of the  g r a i n t h y r o i d was  k  determined over a . p e r i o d of seven days,  t e s t s b e i n g made d a i l y . 5. with  1 mg.  The  e f f e c t of % grain t h y r o i d i n  of r i b o f l a v i n was  now  d e t e r m i n e d by  t e s t s o f t h e B.M.R.s f o r a p e r i o d was  continuous w i t h 4.  the  combination  of  making d a i l y  eleven days. This  test  preceding t e s t .  A s e c o n d g r o u p o f s i x r a t s were p r e t r e a t e d  i g r a i n t h y r o i d f o r 10 d a y s , a f t e r w h i c h t h e y r e c e i v e d grain thyroid chloride  s u p p l e m e n t e d w i t h 1 mg.  with 4-  of thiamine hydro-  f o r n i n e days. 5. A t h i r d g r o u p o f s i x a n i m a l s , a f t e r b e i n g .  f e d i g r a i n t h y r o i d d a i l y f o r t e n d a y s , were g i v e n t h e ... amount o f t h y r o i d d a i l y s u p p l e m e n t e d w i t h 1 mg. hydrochloride f o r a nine-day 6.  One  the  l/lO grain  e f f e c t of t h e - - g r a i n  of a l l three vitamins,  B l , B2  pyridoxins  period.  g r o u p ofl s i x r a t s , u s e d p r e v i o u s l y  investigation with t e s t the  of  same  t h y r o i d , were now  thyroid and  B6.  against a  in  the  used  to  combination  T h e y w e r e p r e - f e d -J-  grain t h y r o i d d a i l y f o r eight'days, a f t e r which t h e i r diet was  further  supplemented w i t h  f o r n i n e d a y s , and ically. e.  1 mg.  o f e a c h o f B l , B2  the b a s a l metabolism determined  ( c f . Tables.7,^/3- /& , g r a p h s $-1%  and  B6  period-  )  Controls Ten  a n i m a l s , not  were u s e d as c o n t r o l s .  used f o r the  These c o n t r o l s  tests outlined  were s e t up  as  above,  follows:  35. 1. F o u r r a t s w e r e u s e d t o a s c e r t a i n t h e e f f e c t on t h e w e i g h t anffl t h e B.M.R. o f s u p p l e m e n t i n g t h e n o r m a l  ration  w i t h 1 mg. o f t h i a m i n e . 2. F o u r r a t s w e r e u s e d t o d e t e r m i n e t h e e f f e c t on t h e w e i g h t a n d t h e B.M.R. o f s u p p l e m e n t i n g t h e n o r m a l r a t i o n w i t h 1 mg. o f r i b o f l a v i n . 3* Two r a t s w e r e u s e d t o d e t e r m i n e t h e e f f e c t on w e i g h t a n d B.M.R. o f s u p p l e m e n t i n g t h e n o r m a l r a t i o n w i t h 1 mg. o f p y r i d o x i n e . 4. Two. r a t ' s , p r e v i o u s l y u s e d , were u s e d t o d e t e r m i n e t h e e f f e c t on w e i g h t a n d B.M.R. o f s u p p l e m e n t i n g t h e n o r m a l , r a t i o n w i t h 1 mg. o f e a c h o f B l , B 2 , and B 6 . 5. Two r a t s , p r e v i o u s l y u s e d , w e r e g i v e n t h e n o r m a l r a t i o n w i t h o u t a n y f u r t h e r supplements' o f v i t a m i n s . These r a t s s e r v e d as c o n t r o l s t o show t h e e f f e c t on w e i g h t due t o t h e n o r m a l r a t i o n a l o n e . The c o n t r o l a n i m a l s r e c e i v e d s i m i l a r r a t i o n s t o a l l t e s t a n i m a l s , a n d the. same e x p e r i m e n t a l c o n d i t i o n s were observed i n making t h e metabolic determinations,  (cf.Tables  if a - ju , graph/3 )  .  RESULTS  The r e s u l t s a r e p r e s e n t e d a s t a b l e s a n d g r a p h s w h i c h f o l l o w . T h e w e i g h t s o f t h e r a t s a r e g i v e n i n grams, t h e t e m p e r a t u r e i n d e g r e e s c e n t i g r a d e and t h e b a s a l m e t a b o l i c r a t e i n c a l o r i e s p e r s q u a r e m e t r e o f body s u r f a c e per hour.  •P  •p  Oh  Ph  • * -  o  to  to 03  « '  o> to 03  O to  to to  to 03  ID »  LO Ol  «  to LO 03  03 03  •  o> CO 03  03  «  to 03  LO  03  ,  E03  « o to  03  r-i  03  H to  LO 03  LO rH 03  CD  LO « to to  CO 0> 03  «  •-  03 « o to  o o to  CO e •  CO H to  o  ov 03  r-i  CO  to  05 CO H  CO  to  «  CO 03  O 03 03  O CO 03  to 03 to  to *  «  H e 03 to  03 03 03  r-i r-i  «  H  ^1  *  ©  bGceJ ctf • to  ft)  © . >  CQ -P  H •H ©  P3  -P  •rl  ff) •P  o  to 03  to to  *  to  O  CO CO  H  to 03  co r-i  CO Or  03  to  LO o> . 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PQ  ft  'OH H 03 '+&  *0 to O 03  ft  -P  to 03 03  •  •p  9 P-  s EH  -P  o tc| !h  cd  p" 03  o  »  •  •  • > * > « ' * ' •  «  tOO3C0HJ>Cr>C0a>C0 O O O r i H H r i r o f f l t003tOtOtOtOtOC303  *»  »  *  ft  «  ftftft  «  tOO03£>0>tOC0CQiH  »  CO  • ft  O  CD tO • (M' O t o t o to to  CD CD CO H  © r o o d O H 03 o> o 03 0 3 t O t O t O t O t 0 0 3 t O  lO t O ^  03 tO 03 • to to t o  to to  ^  a  o . k  6  e  •  •  »  •  CT>tOO3HC0tOtOC3tO cOLO£~C0I>C0CDlOCO O3O303O2O3O3O3O3O3  •  • r  • * ' * -4  • • »  t O H ^ O ) ( D H O C O t O O l O H O M C O l O H O ) w t o t o t o t o t o t o t o w  03 «  «  0 ! > t O  Z> 03 H CO tO 03 tO t o • » * • « CO CT> O O C5> 0> O O V C O 03O3tOtOO3'O3t00303  0 3 t O c 0 0 0 i « ft ft ft < ft ft «  tO CO H 03 t o LO H a> t o o j t o t o t o t o t o t o o j  O j L O t O H H ^ t O ^ t O O C5> H 03 t O r H 03 0> £ tO 03 tO tO t O tO tO 03 03  c o c o c o c ^ ! > t ~ c o ; > c o  O 3 O 3 O 3 O 3 O 3 03 03 03 O3  G D O H O J t O ^ L O C D C H0303030303030303  37.  o C5  0  o LO  c  • to  i-f  Oil  P •a LO to  • 03 03  CO o 03  . r-i  to LO OJ  to to  co  02  CO  LO  to o 03  r-i to  ..faC  -P  CQ  ©  o to  05 03 03  •r-i  to LO  to to H  r-i co to  ;C0  O  to  CO to  03  o  CO » 05 to  •  L> to  o 03 03  •  J> H  05 to  03  03  r-i  H  to  «  03 03  •  to to  * o  $  to  £-  03  1  •  r-i  LO  »  CO LO  o H 03  m  03  c03  «  r-i to LO 03  05  O to  to 03  to  •  LO o 03  to  to  •H ©  r-i LO to  »  co  03  *  K CO to  o  03  •  * CO to  CO  O LO to  LO 03  o to  CO o OJ  c<5  o  to  t*  05 to  03 s  Of-:  o  to  «  O  r-i  03 » CO to  r-i  o •p • H ©  CQ  •ri  ©  p  H O tto  O  «  LO H  © ©  faO OJ  tt  -p  LO  •  LO  r-i  to  ft  CO  co  ft '  03 CO LO  03 CO  o>  CO  ft  LO 9  rH  -  ft '  03  CO  ft  03  LO  03 rH  rH ft •  ft  1  to .  H ft "  co CO  CO CO  ft  to  ft £-  £ft  03  £>  03  to  fc-  «  03  co to  ft ••  o  LO  rH  CO  rH  0  to  CD co  tO CO to  rH  ft co  a> CD  1  tH  ;  ft -  LO to  * CO co  ft  03 CO CO to  o  03  03 03 03  o 03 to  c~ c o -.-  CO 03  03  co  to o 03  to  ft  CO  O 03  CD CO  »  03 1  to  « •  LO to  ft  ujr:  to  ft  LO,  ft  to  rH  to  rH  £-  rH  CD CD  H rH  CO  LO  rH  03  03  co  H  CO  ft '  to  tt  CD • ft -•  to  to  CO 03  •H  03  rH rH  CO"* 03-  03  O rH  rH  o  to ft 1* CO to  1  to CO  H  LO  to  rH  1  CO to  03  ft  CD  to CD  rH  LO co  .'•  ft  o LO  03  rH  03  ft  LO  H  1  rH H  CD  ft -  to o LO  to o  «  rH CO CO  ^  CO  to  ft .  to  03 CO  CO 03  « •  CO  o> 03  CO  OS LO  CO 03  I>  fcc!  ccS © tt IBs  <D  into -p as tt  re ta  0*£a,  tt  - P bD| H K  <s  ©  bC]  otfxl, -P  tt  ©  CD  40  Table 4 V a r i a t i o n I n t h e B.M.R. d u e t o t h e Diurnal Factor Rat  Q_  5-  Time  B;.M.R.  CT  5  (f  c,  Q  ^  G  B.M.R.  B.M.R.  B.M.R.  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C D t O CO CO LO CD CD CO t 0 3 0 3 0 3 0 3 0 3 <H r H CO  to O ^ •sH "5f ^ ^  0 0 t > -<0 r-i CO CD CO S> ^ LO CO CO 0 3 OS 0 3 0 3 0 3 r H I > rH. 03  ^  0 3 LO  » ft • ft ft ft  CO t O CO LO ^  OJ H  ^5  CO CD t O r H DCO !> ^ LO CD CD 03 0 3 03 0 3 0 3 H ^ ^ O H CO CO ft « ft ft ft ft CO 0 3 CO CD CO C~ to ^ ,TH.  d  T a b l e 11 - R e p e a t e d D a i l y Doses o f l / l O g r a i n Desiccated Thyroid together with 1 mg. o f R i b o f l a v i n C  Temp. 28 'C Days 0 Rat  5  .BMR  Wt.'  0*1  39.4 275 34.0 279 41.5 250  ©p'lj-  49.2  (pi Cft t  182  0* "> 36.9 262 0^ r/: 59.4 275 Av.  40.7 254  BMR  7 ,Wt. ; BMR  35.6 279 32.8 276 38.1 242 47.8  9 Wt.  Wt*  32.2 282 34.0 279 39.5 250  179  46.3  287 286 269  183  10 BMR  Wt.  31.8 288 32.4 290 38.1 268  199  41.1  30.2 266 39.1 267  28.7 270 58.1 268  282 277  27.8 283 57.2 276  197  37.3 252  36.5 255  267  34.7  267  T a b l e 12 - R e p e a t e d D a i l y D o s e s o f l / l O g r a i n Desiccated Thyroid together with 1 mg. o f P y r i d o x i n s H y d r o c h l o r i d e Temp. 28 °G Days 0  3  R a t ..' BMR  Wfc.. ..  BMR  0^7 CP 1  280 265 248 172 260 257  7  Q, io <¥>  il  Av.  37.2 36.7 38.0 52.8 37.7 38.5  40.1 247  6  7  10  w t . •'  BMR  Wt.  BMR  Wt.  35 • *7283 •'. 36.9 279 39.2 245 45.9 186 34.9 281 34.6 272  279 280 249 189 278 275  31/4 37.6 40 ;.5 46.4 36.1 35.7  272 273 248 179 271 262  33.1 39.2 38.3 43.0 35.4" 34.2  270 273 257 188 270 266  37.9 258  258  37.8 251  wt.  :  37.2 254  46.  T a b l e 15 - R e p e a t e d D a l l y Doses o f |- g r a i n ., , Desiccated Thyroid together with 1 mg. o f P y r i d o x i n e H y d r o c h l o r i d e Temp. 28°C Days; Rat,;,,  . 0  -  • ' •. -4  B.M.R:. /Weight  7  Cf .'* <f"+ CT if Q. <b (y 'i (y.'-i  Average  B.M.R.  Weight  \  9 B.M.R.  Weight  33.1 234 38.1 247 32.3 394 48.8, 214. 37.9 229  32.4 43.9 34.5 45.3 36.4  239 245 393 213 231  34.7 44.8 .33.0 44.5 32.3  238 246 387 218 230  34.8  33.2  261  34.0  259  260  57.5 265  . 57.6 264  37.2 263  T a b l e 14 - R e p e a t e d D a i l y Doses o f \ g r a i n Desiccated Thyroid together with 1 mg. o f T h i a m i n e H y d r o c h l o r i d e Temp. 28°C Days .  0  Rat  :  <y "?  Average  B.M.R„.  ;  4 Weight  B.'M.R.  Weight  ' 36.1 37.4 58.4 40.9 42.7 45.3  306 258 386 231 204 194  39.5 .35.9 38.9 39.0 ' 42.0: ,43.9  298 260 391 226 207 195  40.1  263  39.5  .266  ;  9  :  B.M.R.  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LO CD . ft Iftft CO  LO t - CO CO 0 5 0 5 0 5 35 CO H r H rH 03 03  03 H - ft ft  LO CD LO  to to. co  LO CO 03  ft• ft  —i  CD  03  O O  ft  CD [CO CO  to  03  0 3 CO O co 0 3 02 03 <tf r H r H H 03 0 3  «  LO 0 3 1  to LO to to to  - *  O to  •>  >  05 jtO 0 3  05 05 05 CO CO CO CO rH rH 03 0 3  «;  oVo*  coLO co to co  a ft  cd  PQ  ft m K  O 0 CO 03  © cd  o  Pi  cd  EH.P  +3  © IOr04<.  .. o ;co  h# C 3  © VXt r H  [LO.05 05 03 r H  LO r H CO CO CO  'ft  K\3 0 3  ^DlCO H o  03 O to ^  CD  a  03 rH  CO  o  LO  0>  03 03 0 3 CD rib  tt ft tO to  £- o o to 03 03  •ft'  0 3 <tf - .ft -  LO 0 5  to to  rH rH  03 03  '© to  ft  03 t O • «  •sH O tO  £H CO <H H 03  03  to CO to t o  it— c*  cd P  48.  T a b l e 17c - Normal D i e t S u p p l e m e n t e d . 1 mg. P y r i d o x i n e  with  Temp. 28°C Days:  0  3  9  12  'Rat  BMR' W e i g h t  BMR .;Weight  BMR  Q. '7  34.3 40.1 3Y .'d  36.2 38.7 37*5  35.2 179 37.3 202 "36.3" 191  Av.  174 196 13b  186 204 195  Weight  BMR  Weight  37.3 180 42.7 204 40.0" 1 9 1 5 —  T a b l e 17d - N o r m a l D i e t S u p p l e m e n t e d w i t h 1 mg. o f e a c h o f V i t a m i n s B1,B2 and B6 Temp. 28«G fays.:: Rat 0  3o %q  rAV*,/  :  0  1  6  BMR  Weight  Weight  BMR  37.3 34.2 35.7  204 180 X92  206 185  40.3 38.2  195  11  •Weight' BMR 215 199  Days  0  RatWeight 0. •\i g. Av.  169 196 " 182  39.0 35.3  39.3' 2 0 7  T a b l e 17e - N o r m a l D i e t w i t h o u t Supplements  Weieht 224 215  37.2—320  Vitamin  5  6  9  10  Weight  Weight  Weight  Weight  182 214 198  184 213  181 209 190"  178 210 OTP"""  ",  1  T  4  -  50.  DISCUSSION •  /  Animals All breeding  a n i m a l s u s e d were t h e o f f s p r i n g o f f o u r  animals obtained  from t h e Wistar  Institute,  Phila-  d e l p h i a , i n S e p t e m b e r , 1942. No r a t s u s e d were u n d e r f o u r months o f a g e , t h e m a j o r p a r t o f t h e w o r k b e i n g done when t h e y were f r o m s e v e n t o t e n months o f a g e . The r a t s a p p e a r e d t o be i n n o r m a l h e a l t h , a l t h o u g h  a few d e v e l o p e d a c o n d i t i o n  s y m p t o m a t i c o f v i t a m i n B2 d e f i c i e n c y . E v i d e n c e o f t h e c o n d i t i o n appeared as l o s s o f h a i r , r e d d e n i n g  and f o r m a t i o n  o f a s c a r a r o u n d t h e e y e . Not more t h a n one eye was a f f e c t e d and  i t was o b s e r v e d t h a t t h e c o n d i t i o n d i d n o t r e a p p e a r  a f t e r t h e a d m i n i s t r a t i o n o f r i b o f l a v i n . B2 c l e a r e d up t h i s c o n d i t i o n i n two o f t h e a n i m a l s so a f f e c t e d . Though some o f t h e t e s t a n i m a l s were f e d t h y r o i d c o n t i n u o u s l y f o r a p e r i o d of almost seven weeks, a l l a n i m a l s s u r v i v e d , a l t h o u g h  some  w o r k e r s ( f\<) have r e p o r t e d a f a i r l y h i g h i n c i d e n c e o f m o r t a l i t y among r a t s a s a r e s u l t o f t h y r o i d t o x i c i t y  induced  b y t h y r o i d f e e d i n g . T h a t t h i s was n o t f o u n d t o o c c u r ,  may  be a t t r i b u t e d t o t h e f a c t t h a t t h e r e I n t e r v a l s o f v i t a m i n f e e d i n g , w h i c h , i t i s b e l i e v e d , tended t o o f f s e t t h e t o x i c i t y r e s u l t i n g from the induced hyperthyroid  condition.  Apparatus The e x p e r i m e n t a l  c o n d i t i o n s under which t h e t e s t s  51. were made w e r e as u n i f o r m as p o s s i b l e . I t m i g h t be emphas i z e d here t h a t a c o n s i d e r a b l e source of e r r o r w i l l  arise  u n l e s s c a r e i s t a k e n t o r e p l e n i s h t h e soda l i m e u s e d t o a b s o r b t h e c a r b o n d i o x i d e and m o i s t u r e f r o m t h e a n i m a l chamber. T h i s i g r r o r c a n e a s i l y l e a d t o a m i s i n t e r p r e t a t i o n of  r e s u l t s , s i n c e f a i l u r e t o a b s o r b t h e carbarn d i o x i d e  will  g r e a t l y r e t a r d r e s p i r a t i o n i n t h e a n i m a l chamber. As menti o n e d p r e v i o u s l y , i t i s recommended t h a t t h e s o d a l i m e  be  r e n e w e d a f t e r n o t more t h a n 48 t w e n t y m i n u t e r u n s , o r , i f t h e a p p a r a t u s i s i n f r e q u e n t l y u s e d , a t l e a s t once e a c h week. A f t e r u s i n g , t h e s o d a l i m e s h o u l d be p l a c e d i n t h e d r y i n g o v e n . The k i n d and q u a l i t y o f s o d a l i m e s h o u l d be the:  same> t h r o u g h o u t t h e i n v e s t i g a t i o n .  F a c t o r s A f f e c t i n g the B a s a l M e t a b o l i c Rate a. P a s t i n g As t h e v a l u e s i n T a b l e l a show, t h e m e t a b o l i c r a t e showed a marked d r o p f r o m c e s s a t i o n o f f e e d i n g t o t h e 18th  hour p o s t - a b s o r p t i o n . A s t i l l  lower value f o r the  B.M.R. w a s - o b t a i n e d a f t e r 30 h o u r s f a s t i n g . A t t h e 2 4 t h h o u r , h o w e v e r , a v a l u e s l i g h t l y above t h a t a t 18 h o u r s was  f o u n d . The  the  f i n d i n g s o f Kingdon,Bunnel and G r i f f i t h  the  r i s e i n . t h e BMR  a s  r e s u l t s a r e t h e r e f o r e i n agreement w i t h (3<>) a l t h o u g h  f r o m t h e 1 8 t h t o t h e 2 4 t h h o u r wasenot  pronounced. T a b l e l b shows t h e r e s u l t s o f t h e  subsequent  t e s t t o determine the f a s t i n g metabolism of the r a t from  the 1 9 t h t o t h e 2 7 t h hour , making h o u r l y d e t e r m i n a t i o n s t h e B.M.R. a n d u s i n g s e v e n r a t s . T h i s t e s t c o n f i r m e d t h e p r e v i o u s one, a s l i g h t l y  h i g h e r v a l u e "being f o u n d a t t h e  24-th h o u r o f f a s t i n g . Kingdon,Bunnel a n d G r i f f i t h l o o k on t h e low metabolism  o b s e r v e d a f t e r 18 h o u r s  midway b e t w e e n t h e m e t a b o l i s m  f a s t i n g as b e i n g  o f mixed f o o d s t u f f s and  one  e x c l u s i v e l y o f f a t , b y which they attempt  for  t h e h i g h e r m e t a b o l i c r a t e a f t e r 24 h o u r s  e x p l a n a t i o n has support  t o account fasting. Thi  i n t h e work o f Benedict  ( 3 ) , who  stated that ther e s p i r a t o r y quotient of ther a t , fasted 24 h o u r s , i s .72 , w h i c h  i s t h e R.Q.. when f a t a l o n e i s  m e t a b o l i z e d b y t h e b o d y . These r e s u l t s a r e o f i n t e r e s t since they help t o c l a r i f y the apparently c o n t r a d i c t o r y r e s u l t s o b t a i n e d when t h e d e s i c c a t e d t h y r o i d was a d m i n i s t e r e d t o t h e f a s t i n g r a t . ( c f . T a b l e 5,graph 5 ). I t i s concluded from t h i s t e s t , t h a t since t h e B.M.R. does n o t a p p e a r c o n s i s t e n t a f t e r 18 h o u r s  fasting,  i n m a k i n g a s e r i e s o f d a i l y d e t e r m i n a t i o n s o f t h e B.M.R., t h a t t h e same i n t e r v a l o f f a s t i n g b e a l l o w e d between e a c h determination. b. E n v i r o n m e n t a l The  Temperature  a v e r a g e B.M.R.s o f ; t h e s i x r a t s u s e d a p p e a r  i n T a b l e 2, page 3 8 , a s f o l l o w s - . Temperature .Average,B.M.R.,  21°C 27°C 40.15 37.01  3±.5°C 39°C 37.71 58.3  53. The V a l u e s show a d e f i n i t e d r o p i n t h e B.M.R. a t 27"C as compared t o 21"C, i n d i c a t i n g t h a t a t 21°C t h e m e t a b o l i s m i s n o t b a s a l , what p r o b a b l y c o n t r i b u t e d t o t h e h i g h e r v a l u e a t 21°0 i s t h a f a c t t h a t a t t h i s  temperature  i t was d i f f i c u l t t o c o n t r o l t h e a c t i v i t y o f t h e a n i m a l . A t 27°C, w h i c h i s somwwhat h i g h e r t h a n t h a t o f t h e r a t ' s environment  (25.5^0), a c t i v i t y i s p r a c t i c a l l y n i l .  normal  As many  w r i t e r d h a v e p o i n t e d o u t , b a s a l m e t a b o l i s m does n o t e x i s t when t h e r e i s a c t i v i t y p r e s e n t . The h i g h e r m e t a b o l i s m a t 21 C i s i n p a r t a t t r i b u t a b l e t o t h e g r e a t e r t i s s u e m e t a b o l i s m w h i c h o c c u r s t o h e l p m a i n t a i n t h e body temperature i n t h i s lower environmental temperature. B e n e d i c t a n d MacLeod ( j f ) r e p o r t e d t h a t 28°C was the temperature o f thermal n e u t r a l i t y f o r the albino r a t . S w i f t and Forbes  set a s l i g h t l y h i g h e r temperature o f  30"G a s t h i s " c r i t i c a l t e m p e r a t u r e " . The r e s u l t s o b t a i n e d i n d i c a t e t h a t t h e B.M.R. i s o n l y s l i g h t l y a f f e c t e d b y a n i n c r e a s e i n t e m p e r a t u r e f r o m 27°C t o 31°C. A t a t e m p e r a t u r e o f 39°G, t h e m e t a b o l i s m  showed  a c o n s i d e r a b l e i n c r e a s e ( 5 7 . 5 % o v e r t h a t a t 21°C). The i n f e r e n c e f r o m t h i s h i g h v a l u e i s t h a t above a c e r t a i n t e m p e r a t u r e , i n t e r m e d i a t e b e t w e e n 31.5°C a n d 39"C, e x t e r n a l h e a t h a s a t h e r m o g e n i c e f f e c t on m e t a b o l i s m . The a n i m a l s a p p e a r e d t o s u f f e r f r o m t h e h i g h t e m p e r a t u r e , became i n e r t , and showed a d i m i n i s h e d f o o d i n t a k e f o r a f e w d a y s . I t may t h e r e f o r e be i n f e r r e d f r o m t h e above r e s u l t s , h o w e v e r  meagre  t h e y are> t h a t t h e r e i s a m a x i m a l t e m p e r a t u r e b e l o w w h i c h  . the  ...  -  , 54.  h e a t p r o d u c t i o n v a r i e s i n v e r s e l y as t h e t e m p e r a t u r e , and  a m i n i m a l t e m p e r a t u r e abarve w h i c h t h e r e i s a t h e r m o g e n i c e f f e c t , a c c e l e r a t i n g metabolism u n t i l death r e s u l t s . .The e x p e r i m e n t a l c o n d i t i o n s f o r c o n d u c t i n g t h i s e x p e r i m e n t were i d e a l . The a n i m a l s were p l a c e d i n t h e e x p e r i m e n t r o o m f o r u p w a r d s o f one h o u r b e f o r e t h e r u n s were made and were t h u s a d j u s t e d m e t a b o l i c a l l y t o t h e e n v i r o n m e n t a l t e m p e r a t u r e . The room t e m p e r a t u r e was t h e same as t h a t o f t h e a n i m a l chamber d u r i n g t h e r u n . c Age The r e s u l t s o f t h e i n v e s t i g a t i o n t o d e t e r m i n e t h e v a r i a t i o n i n t h e B.M-.R. a s i n f l u e n c e d b y age a r e shown i n T a b l e 3, p a g e 3 9 . The a v e r a g e v a l u e s show a f a i r l y  steady  drop i n t h e b a s a l v a l u e s w i t h i n a short space o f time. I t is  t o be r e g r e t t e d t h a t - t i m e d i d n o t p e r m i t c o n t i n u a t i o n o f  t h i s p o r t i o n o f t h e i n v e s t i g a t i o n , beyond t h e 1 2 t h week. The r e s u l t s show a s h a r p d r o p i n the-B.M.R. f r o m t h e 6 t h to  t h e 9 t h week, a f t e r w h i c h t h e v a l u e s a p p e a r e d  fairly  c o n s i s t e n t t o t h e 1 2 t h week. W e e k l y d e t e r m i n a t i o n s were n o t c a r r i e d on a f t e r t h e 1 2 t h week, b^ct v a l u e s o b t a i n e d at  28 weeks o f age show t h a t t h e d r o p f r o m t h e 1 2 t h week  i s n o t c o n s i d e r a b l e . A c o m p a r i s o n o f t h e B.M.R.s t o t h e growth gains i n d i c a t e s t h a t the g r e a t e s t a c c e l e r a t i o n i n g r o w t h o c c u r r e d d u r i n g t h e f e w weeks when t h e m e t a b o l i s m was h i g h . .  d. Time o f D a y The  r e s u l t s f r o m T a b l e 4,page 4 0 , show a v e r y  s l i g h t v a r i a t i o n i n t h e B.M.R. m e a s u r e d a t 10 A.M.,at 12 A.M. and a t 5 P.M. Prom 10 A.M. t o noon t h e r e i s a r e d u c t i o n o f l.dfo  i n t h e a v e r a g e B.M.R. s, and a t 3 P.M. t h e r e i s a r i s e  o f 4.1$ o v e r m i d d a y . T h i s v a r i a t i o n i s s l i g h t a s compared w i t h t h e v a r i a t i o n . d u e t o o t h e r f a c t o r s such as temperature and. f a s t i n g . ' W h i l e t h e d i u r n a l v a r i a t i o n may b e p r o n o u n c e d when o t h e r v a r i a b l e s o r d i n a r i l y e n c o u n t e r e d , temperature,feeding y e t where a n a t t e m p t  such as  t i m e s , and a c t i v i t y have t o b e c o n s i d e r e d i s made t o m i n i m i z e  these v a r i a b l e s  by e x p e r i m e n t a l a n d l a b o r a t o r y c o n d i t i o n s , t h e d i u r n a l v a r i a t i o n c a n be e x p e c t e d the environmental throughout  t o be s m a l l . F u r t h e r , s i n c e  c o n d i t i o n s o f t h e colony r a t s are u n i f o r m  t h e y e a r , i t followed t h a t s e a s o n a l  variations  can l i k e w i s e be e l i m i n a t e d from m e t a b o l i c d e t e r m i n a t i o n s . Desiccated Thyroid a.. A d m i n i s t e r e d a f t e r F a s t i n g The  v a l u e s o f t h e "B.M.R.S a f t e r t h y r o i d  r a t i o n s to. t h e f a s t i n g anima^L'eaflSB shown i n T a b l e  administ5,page 4 1 .  From t h e 1 8 t h t o t h e 2 4 t h h o u r p o s t - a b s o r p t i o n , t h e B.M.R.s show a r i s e ( c f .  g r a p h 5 ) . T h a t t h i s e l e v a t i o n i n t h e B.M.R.  can.not be regarded  as t h y r o i d s t i m u l a t i o n o f t h e m e t a b o l i s m  i s d e m o n s t r a t e d b y t h e B.M.R. v a l a e s o b t a i n e d f r o m t h e 2 4 t h t o t h e 2 7 t h hour o f f a s t i n g . Comparing t h e curves  obtained  i n g r a p h 5, w i t h g r a p h 1, s h o w i n g t h e . h e a t p r o d u c t i o n o f t h e f a s t i n g a n i m a l , i t a t once becomes a p p a r e n t  that the  56. administration of l / l O grain desiccated  thyroid t o the  f a s t i n g a n i m a l h a s p r a c t i c a l l y no i m m e d i a t e e f f e c t . Thus t h e r e s u l t s o b t a i n e d g r a i n dose administered explained  b y Cooper f o r t h e  24 h o u r s p o s t - a b s o r p t i o n  l/lO  may b e  o n t h i s b a s i s . The l e v e l l i n g o f t h e c u r v e f o r t h e  l / 5 t h and|r ,grain doses o f t h y r o i d a l s o lends support t o t h i s explanation,,  s i n c e these l a r g e r , doses might f e a s i b l y  s t i m u l a t e m e t a b o l i s m of t h e d i g e s t e d  and reserve  t o m a i n t a i n t h e 24 h o u r b a s a l m e t a b i l i e  f a t s so a s  r a t e , which•would  o t h e r w i s e have a tendency t o d r o p , b.  Administered before  Fasting  V a l u e s i n T a b l e 6, page 42, that the  B.M.R. i s e l e v a t e d  a n d g r a p h 6, r e v e a l  somewhat b y t h e  of a l / l O g r a i n dose o f d e s i c c a t e d  administration  t h y r o i d . The m a x i m a l  v a l u e s w e r e f o u n d 24 a n d 48 h o u r s a f t e r a d m i n i s t e r i n g t h y r o i d . A comparison o f the  the  two d r u g s i n d i c a t e s t h a t t h e  P a r k e D a v i s l / l O g r a i n t h y r o i d i s more a c t i v e p h y s i o l o g i c a l l y than t h a t o f Burroughs Wellcome. .  The a d m i n i s t r a t i o n  desiccated  t h y r o i d p r o v e d e f f e c t i v e i n e l e v a t i n g - t h e B.M.R.  to a higher page 4 3 ) .  o f a s i n g l e dose p f \ g r a i n  degree t h a n the  This  l / l O g r a i n t h y r o i d ( c f . T a b l e 7,  e f f e c t p e r s i s t e d o v e r a p e r i o d o f s i x days  a f t e r w h i c h t h e B.M-.R. was f o u n d to• r e t u r n t o n o r m a l . ;  From t h e r e s u l t s , i t a p p e a r s t h a t , t h e s i n g l e dose  o f l / l O and i g r a i n t h y r o i d , a d m i n i s t e r e d stimulatory  o r a l l y , has a  e f f e c t , n o t a p p a r e n t i m m e d i a t e l y , o n t h e B.M.R.  s  and w h i c h h a s i t s m a x i m a l e f f e c t f r o m 2 4 t o 48 h o u r s f o l l o w ing i t s administration. Vitamins ,  and t h e T h y r o i d  a . B1,B2,B6. a n d l / l O g r a i n T h y r o i d The  r e s u l t s o f these  tests to ascertain the  e f f e c t s o f tatamins B1,B2 a n d B6 on t h e B.M.R. a f t e r  inducing  a hyperthyroid condition, by feeding l / l G grain thyroid daily, are-shown i n T a b l e s  9-12,pages 44 and 45,and i n g r a p h 7 *  The  vitamins  although  g i v e n s i n g l y and a t i n t e r v a l s , a p p a r e n t l y  had  a summation e f f . e c t i n r e d u c i n g t h e B.M.R., s i n c e a t no  t i m e d i d t h e B.M.R. a p p r o a c h t h e peak a t t a i n e d a f t e r t h e I n i t i a l p e r i o d o f f e e d i n g t h e t h y r o i d ( T a b l e 9%. The 'continuous  f e e d i n g o f t h e t h y r o i d f o r t h e 46 d a y p e r i o d  a l s o appeared t o have had a c u m u l a t i v e of t h e animals,  e f f e c t on t h e w e i g h t s  s i n c e a t no p o i n t d i d t h e w e i g h t s r e t u r n t o  n o r m a l . R i b o f l a v i n h a d t h e most p r o n o u n c e d e f f e c t i n augmenting the weights The  r e s u l t s , as judged b y t h e a n t i t h y r o g e n i c  effect o f the vitamins  i n c o u n t e r a c t i n g w e i g h t l o s s and  i n c r e a s e d m e t a b o l i s m may b e summed u p f r o m T a b l e s  $-11 a s  follows: % change i n w t . B l and' l / l O g . B2 " " B6 " " l/lO g.thyroid  •  $ c h a n g e - i n B.M.R.  1.2 g a i n - 5.3 " 2.8 "  12.3 d e c r e a s e 14.7 " 7.2 "  7.4 l o s s  16.3 i n c r e a s e  As t h i s summary shows, a l l t h r e e v i t a m i n s h a v e a l o w e r i n g e f f e c t on t h e B.M.R. i n c r e a s e d 16.3$; above n o r m a l .  58. The e f f e c t s o f t h i a m i n e  and r i b o f l a v i n were most m a r k e d i n  t h i s r e s p e c t . The e f f e c t i n c o u n t e r a c t i n g w e i g h t l o s s was found to"be s l i g h t i n the case of thiamine and more marked i n t h e c a s e . o f  and'pyridoxine  riboflavin,  b . B1,B2,B6 and f- g r a i n t h y r o i d The r e s u l t s o b t a i n e d Tables  i n these  13 - 16,pages 46 and 4 7  t e s t s a r e shown i n  and as©- pr-epeHted h e r e i n  9  summary f o r m : Rats given  $c;gange i n w t .  •j- g . t h y r o i d o n l y .  % change i n B.M.R.  11.7 l o s s  IT g . t h y r o i d a n d B l ' B2 " B6 " B1,B2 & B6  0.0 l o s s 5.25 g a i n 0.84 l o s s 7.80 g a i n  23.4  increase  .8 15.5 0.0 14.5  decrease decrease decrease decrease  The a d m i n i s t r a t i o n o f t h e i g r a i n t h y r o i d was found t o e l e v a t e t h e metabolic  r a t e t o 23.4%' above n o r m a l ,  and .to p r o d u c e a weight' l o s s o f 11.7%' b e l o w n o r m a l . These p e r c e n t a g e s a r e b a s e d on t h e a v e r a g e v a l u e s o b t a i n e d three groups of animals, t o the thyrogenie  comprising  eighteen  rats.  from  Compared  e f f e c t r e s u l t i n g from the a d m i n i s t r a t i o n  of the l / l O g r a i n t h y r o i d , i t appears that the increased h y p e r t h y r o i d c o n d i t i o n i s not p r o p o r t i o n a l t o the increased d o s e . I t h a s been r e p o r t e d t h a t much o f t h e p o t e n c y o f t h e thyroid, given o r a l l y , I s l o s t in,the t r a c t , w h i c h would-make logical  i tdifficult  gastro-intestinal to predict the physio-  a c t i v i t y r e s u l t i n g from a g i v e n dosage. The a n t i t h y r o g e n i e a c t i o n o f t h i a m i n e  d o x i n e wase l e s s e v i d e n t  i n these  and p y r i -  t e s t s . No g a i n i n w e i g h t  59. was  o b s e r v e d f o r t h i a m i n e , b u t t h e w e i g h t was m a i n t a i n e d a t  the I n i t i a l  l e v e l . The B.M.R. showed a ..slight r e d u c t i o n o f  0.80$ . P y r i d o x i n e was f o u n d t o be even l e s s e f f i c i e n t i n c o u n t e r a c t i n g the heightened  m e t a b o l i s m and w e i g h t l o s s . As  t h e above t a b l e shows.., no change i n t h e B.M.R. o c c u r r e d t h e r e was a s l i g h t  reduction i n weight.  R i b o f l a v i n p r o v e d t o have t h e  greatest antagonistic  e f f e c t f o r the t h y r o i d a c t i v i t y , l o w e r i n g the metabolic 15.5$  and.  rate  a n d i n c r e a s i n g t h e w e i g h t 5.25$ . The  e f f e c t o f the a d m i n i s t r a t i o n o f the  three  v i t a m i n s had a g r e a t e r e f f e c t i n promoting a weight gain than when ^ i b o g l a v i n . a l o n e was u s e d , a n d a n e a r l y p a r a l l e l  effect  t o r i b o f l a v i n i n l o w e r i n g t h e i n c r e a s e d m e t a b o l i s m . Thus t h e three vitamins'appeared  s y n e r g i s t i c i n augmenting the weight  and. i n r e d u c i n g t h e B.M.R. T h i s seems p l a u s i b l e s i n c e  these  v i t a m i n s w e r e f o u n d t o have a c o m p l e m e n t a r y e f f e c t when t h e i r glycogenetie  f u n c t i o n s were s t u d i e d  Drill B6  (^3).  f o u n d a n addecf r e q u i r e m e n t f o r B1,B2 a n d  i n a h y p e r t h y r o i d c o n d i t i o n . No w o r k e r has. f o u n d a g r e a t e r  r e q u i r e m e n t f o r r i b o f l a v i n than' f o r e i t h e r t h i a m i n e doxine i nt h i s  c o n d i t i o n . The p h y s i o l o g i c a l r e l a t i o n s h i p o f  these v i t a m i n s t o h y p e r t h y r o i d i s m The  or,pyri-  remains t o be i n v e s t i g a t e d .  f o l l o w i n g ' e x p l a n a t i o n , though admittedley  superficial,  i s o f f e r e d b e c a u s e i t i n c l u d e s a f e w o f t h e known f a c t s . The  main storage  i n the body i s the  liver.  d e p o t f o r v i t a m i n s B l , B 2 and B6 The l i v e r h a s l e s s c a p a c i t y t o  60. s t o r e B l o r B6 t h a n i t has  (24).  f o r B2  The  a greater a b i l i t y to retain r i b i f l a v i n .  Since i n the hyper-  t h y r o i d c o n d i t i o n the B vitamin reserves hausted i n the l i v e r ,  i t m i g h t be  l i v e r a l s o shows  are q u i c k l y  ex-  expected t h a t the  s t o r e s w o u l d be d e p l e t e d l a s t . When t h e s e  riboflavin  v i t a m i n s are  s i n g l y t o t h e h y p e r t h y r o i d i n d i v i d u a l , t h e body w o u l d  given be  e x p e c t e d t o show a g r e a t e r r e t e n t i v e n e s s f o r r i b o f l a v i n , whereas t h i a m i n e l o s t . . The  and  p y r i d o x i n e w o u l d be r a p i d l y u s e d  g r e a t e r r e t e n t i v e n e s s o f t h e body f o r B2 v  t h e r e f o r e , i n part , account f o r i t s g r e a t e r  and  may,  antithyrogenie  activity. Controls The: t e s t s on t h e c o n t r o l a n i m a l s from Tables  17 a-e,pages 48 and  Supplement  No. o f Animals  Bl B2 B6 B1,B2 No  & B6  4 4 2 2  .  supplement 2 As  49,  Duration of T e s t s / Days 12,13 12,16 12 .11 10  as  % increase i n Weight  ,.  summarized  follows;  7.2 11.4 3.8 14.3  . $ change f r o m I n i t i a l B.M.R. 6.0 5.1 7.5 4.1  increase decrease increase increase  4.1  t h i s summary shows., t h i a m i n e  tendency to increase the weightj  are  exhibited a  p y r i d o x i n e showed no  slight tend-  e n c y t o i n c r e a s e t h e w e i g h t , as compared t o t h e n o r m a l w e i g h t c o n t r o l s , and r i b o f l a v i n showed a n o t i c e a b l e i n f l u e n c e t h e g r o w t h . The  g r e a t e s t p r o p o r t i o n a t e g a i n was  'feeding a l l t h r e e v i t a m i n s ; s i m u l t a n e o u s l y .  The  showed an u n m i s t a k e a b l e l i k i n g f o r t h e p r e p a r e d  on  produced animals diets  by  61. c o n t a i n i n g t h e v i t a m i n s , s i n c e i t was o b s e r v e d t h a t i t t h i s prepared  f o o d was g i v e n t o g e t h e r w i t h the r e g u l a r d i e t  the f i r s t  t o b e consumed was t h e p r e p a r e d The  c h a n g e s i n t h e B.M.R.s t a b u l a t e d above w e r e  computed f r o m v a l u e s o b t a i n e d periods  diet.  a t the termination o f the  test  a g a i n s t t h e i n i t i a l b a s a l v a l u e s . They a r e n o t  s i g n i f i c a n t , since f l u c t u a t i o n s occurred  periddically  i n t h e B . M . R . s . t h r o u g h o u t t h e t e s t as T a b l e 17 shows, a n d can  o n l y be t a k e n  as s u g g e s t i v e . W i t h t h e e x c e p t i o n o f  riboflavin., the vitamins  appeared t o have a s l i g h t  s t i m u l a t o r y e f f e c t on t h e m e t a b o l i s m . An e x a m i n a t i o n o f /7<J-e.  t h e T a b l e s A a n d g r a p h /3 w i l l  show t h a t t h e v i t a m i n s , h o w e v e r ,  h a v e no a p p r e c i a b l e e f f e c t on t h e B.M.R. SUMMARY C e r t a i n f a c t o r s which govern the b a s a l r a t e were s t u d i e d i n o r d e r t o f i n d e x p e r i m e n t a l under which heat production  metabolic conditions  i n t h e a l b i n o r a t w o u l d be  minimal. I n r e g a r d t o t h e f a s t i n g m e t a b o l i s m , i t was f o u n d t h a t , i n agreement w i t h t h e work o f Kingdon,Bunnel and G r i f f i t h , the metabolic  r a t e d e c l i n e s from c e s s a t i o n o f  f e e d i n g t o t h e "20th h o u r p o s t - a b s o r p t i o n , a f t e r w h i c h t h e r e is  a n e l e v a t i o n i n t h e B.M.R. r e a c h i n g maximum a t t h e  24th  hour f o l l o w e d b y a drop t o the 3 0 t h hour. T h i s r i s e a t t h e 2 4 t h h o u r was a t t r i b u t e d t o t h e m e t a b o l i s m o f f a t .  62. Inaccuracies i n determining the length of the f a s t i n g  period  can t h e r e f o r e l e a d t o a d i v e r s i t y o f r e s u l t s . The h e a t p r o d u c t i o n o f r a t s f a s t e d 20 h o u r s was f o u n d t o b e m i n i m a l b e t w e e n 27"C a n d 31°C.  I t appeared  f r o m t h e r e s u l t s t h a t t h e r e was a " l o w c r i t i c a l "  temperature  b e l o w w h i c h t h e m e t a b o l i s m v a r i e s I n v e r s e l y as t h e e n v i r o n m e n t a l t e m p e r a t u r e and a " h i g h c r i t i c a l " which  t e m p e r a t u r e above  the e n v i r o n m e n t a l temperature has a thermogenic  effect.  V a l u e s o f t h e B.M.R. i n t h e f a s t i n g a n i m a l showed o n l y , a s l i g h t v a r i a t i o n when d e t e r m i n e d a t 10 A.M. a t 12 A.M. :  and a t 3 P.M. The B.M.Rs o f r a t s s i x weeks o f age were f o u n d t o d e c l i n e r a p i d l y t o t h e t e n t h week a f t e r w h i c h t h e y a p p e a r e d to  become more c o n s t a n t . A s c e r t a i n e d when t h e r a t s were  t w e n t y - e i g h t weeks, the, B.M.R. showed a d r o p o f Q% f r o m t h e t w e l f t h week. The  a d m i n i s t r a t i o n o f a s i n g l e l / l O g r a i n dose o f  d e s i c c a t e d t h y r o i d , o r a l l y , was f o u n d t o h a v e a s l i g h t s t i m u l a t o r y e f f e c t o n t h e B.M.R., n o t i m m e d i a t e l y a p p a r e n t , , w h i c h r e a c h e s maximum i n f r o m one t o two d a y s and s u b s i d i n g t o w a r d s t h e t h i r d o r f o u r t h d a y . The s t i m u l a t o r y  effect  p e r s i s t e d l o n g e r when a s i n g l e d o s e o f t h e i g r a i n d e s i c c a t e d t h y r o i d was a d m i n i s t e r e d . R e p e a t e d d a i l y d o s e s o f t h e t h y r o i d was f o u n d t o h a v e a c u m u l a t i v e e f f e c t i n e l e v a t i n g the  B.M.R. a n d p r o d u c e d a w e i g h t The  loss.'  e f f e c t s o f v i t a m i n s B1,B2 a n d B6, s i n g l y a n d  63. i n combination, two  on t h e B.M.R. o f t h e r a t , were s t u d i e d , a t  levels of thyroid feeding. U s i n g l / l O g r a i n Burroughs Wellcome d e s i c c a t e d  thyroid, administered  d a i l y , t h e B.M.R. was f o u n d t o I n c r e a s e  16.3%. T h i s i n c r e a s e d m e t a b o l i s m was r e d u c e d 12.3$ ( 500 I.U.)  thiamine  h y d r o c h l o r i d e p e r day,  1.4.7$ w i t h 1 mg.  o f • . • r i b o f l a v i n [ 400 She r m a n - B o u r q u i n ) u n i t s ) p e r day, w i t h 1 mg. o f p y r i d o x i n e h y d r o c h l o r i d e p e r day. w e i g h t , a m o u n t i n g t o 7.4$, was  induced  w i t h 1 mg.  and 7.2$  The l o s s i h  by the t h y r o i d f e e d i n g ,  p a r t i a l l y r e g a i n e d when a c o m b i n a t i o n  of each o f these  v i t a m i n s was f e d w i t h t h e t h y r o i d . T h i a m i n e r e s u l t e d i n a w e i g h t g a i n o f 1.2$ , r i b o f l a v i n , 5 . 3 $ , a n d p y r i d o x i n e , 2.8$ , The;administration  o f ^ grain desiccated thyroid  d a i l y e l e v a t e d t h e B.M.R. 23.4$ above n o r m a l and r e d u c e d the, w e i g h t 11.7$  b e l o w n o r m a l . 1 mg. o f B l , a d m i x e d w i t h t h e  food and \ grain t h y r o i d , maintained t h y r o i d l e v e l , a n d h a d no a p p r e c i a b l e  t h e v/eight a t t h e  hyper-  effect i nlowering  B.M.R. 1 mg. o f p y r i d o x i n e , p l u s ^ g r a i n t h y r o i d , d i d n o t the metabolic, r a t e and m a i n t a i n e d hyperthyroid level.  the alter  the weight a t about t h e  1 mg. of- r i b o f l a v i n , t o g e t h e r w i t h \  g r a i n t h y r o i d , o f f s e t t h e w e i g h t l o s s w i t h a g a i n o f 5.25$ and d o w e r e d t h e m e t a b o l i s m 15.5$  . Thus r i b o f l a v i n was f o u n d  x  t o p r o d u c e t h e mo st marked a n t i t h y r o g e n i e e f f e c t , b o t h i n o f f s e t t i n g the weight l o s s and i n r e d u c i n g the  increased  b a s a l metabolism. The  a d m i n i s t r a t i o n o f \ g r a i n , t h y r o i d together  64. w i t h 1 mg.  eachi o f " a l l e t h r e e  a w e i g h t g a i n o f 7.8$  of the vitamins resulted i n  and a r e d u c t i o n i n t h e B.M.R. o f 14.5$  s u g g e s t i n g t h a t t h e t h r e e v i t a m i n s have a s y n e r g i s t i c  effect  i n c o u n t e r a c t i n g w e i g h t l o s s and I n c r e a s e d m e t a b o l i s m due t o thyroid  feeding. The a d m i n i s t r a t i o n o f Ihmg*'o£xeach o f t h e  v i t a m i n s as s u p p l e m e n t a r y t o t h e n o r m a l d i e t was f o u n d t o h a v e no a p p r e c i a b l e e f f e c t on t h e B.M.R.., t h o u g h t h e y d i d stimulate  growth.  65. REFERENCES CITED A l t h a u s e n , T.L. The d i s t u r b a n c e o f . c'ap'bohydrat.e m e t a b o l i s m i n Hyperthyroidism." J.'Am. Med. A s s o c . 115:,401, 1 9 4 0 . B a r n e s , B . O . and Bueno,J.Q. The i n f l u e n c e o f t h y r o g l o b u l i n on b a s a l m e t a b o l i s m . Amer. F o u r . P h s i o l . 113, 7, 1935. B B n e d i c t , F.G. A m u l t i - c h a m b e r a p p a r a t u s f o r r a t s and o t h e r small animals. J . N u t . 3, 1 6 1 , 1930. B e n e d i c t , F , G . , and MacLeod,G-. The h e a t p r o d u c t i o n o f t h e a l b i n o r a t . I . T e c h n i q u e , A c t i v i t y - C o n t r o l , and t h e I n f l u e n c e o f F a s t i n g . J . N u t . 1, 343, 1929. Blank,H. T l e r g r o s s e und S t o f f w e c h s e l . P f l u g e r s A r c h . 234, 310, 1934. Cameron, A.T. The t h y r o i d g l a n d and i o d i n e m e t a b o l i s m . R e c e n t Advances' i n E n d o c r i n o l o g y , 7 9 , 2nd e d i t i o n , 1935. P. B l a k i s t o n ' s Son & Co. I n c . , P h i l a d e l p h i a . Cooper,W.D. Studies of t h e b a s a l metabolism of a l b i n o r a t s . D e p t . o f C h e m i s t r y , U n i v e r s i t y of' B r i t i s h C o l u m b i a , T h e s i s , 1942. Cowgill,G.R. V i t a m i n B l and t h e C l i n i c . The V i t a m i n s . A Symposium o f t h e P r e s e n t S t a t u s o f t h e Known V i t a m i n s . Am. Med. A s s o c . 1 6 5 , 1932.  66. (9)  (10)  C o w g i l l , G . R . and P a l m i e r i , M . L . Studies i n the physiology of vitamins: the e f f e c t of experimentally induced hyperthyroidism on t h e v i t a m i n B r e q u i r e m e n t s ' o f p i g e o n s . Amer. J o u r . P h y s i o l . 1 0 5 , 1 4 6 , 1933. Davis,J.E. The e f f e c t o f a d v a n c i n g age on t h e o x y g e n consumption of r a t s . . Amer. J o u r . P h y s i o l . 119, 2 8 , 1937.  (11)  D a i s r i s , J . E . and H a s t i n g s , A . R . The measurements o f t h e o x y g e n c o n s u m p t i o n o f immature r a t s . Amer. J o u r . P h y s i o l o g y , 109, 6 8 3 , 1934. :  (12)  Drill,V.A. E f f e c t o f y e a s t on t h e l i v e r , g l y c o g e n o f w h i t e rats during hyperthyroidism. J . N u t . 1 4 , 355, 1937.  (13)  Drill,V.A. The e f f e c t .of e x p e r i m e n t a l h y p e r t h y r o i d i s m on t h e v i t a m i n B c o n t e n t of'some r a t t i s s u e s . •Amer. J o u r . . - P h y s i o l . 122, 4 8 6 , 1938.  (14)  Drill,V.A. ' The c a l o r i e i n t a k e and weight, b a l a n c e o f h y p e r t h y r o i d dogs i n r e l a t i o n t o v i t a m i n B and y e a s t . • ' Amer. J o u r . P h y s i o l . 1 3 2 , 6 2 9 , 1941. #  (15)  D r i l l , V . A . and;Hays,H.W. - •• H y p e r t h y r o i d i s m and l|.ver f u n c t i o n i n r e l a t i o n to B'vitamins. P r o c . S o c . E x p t l . B i o l . Med. 43,450,1940.  (16)  D r i l l , V . A . and. Overman,R. I n c r e a s e d r e q u i r e m e n t o f p a n t o t h e n i c a c i d and vitamin B6'during experimental hyperthyroidism. Amer, J o u r . P h y s i o l . 135, 4 7 4 , 1942.  67. (17)  D r i l l , V . A . , O v e r m a n , R . and S h a f f e r , G . B . , Carbohydrate Metabolism. ' I . E f f e c t o f B vitamins ' on l i v e r g l y c o g e n o f t h y r o i d f e d r a t s . E n d o c r i n o l o g y 3 1 , 245,. 1 9 4 2 .  (18)  D r i l l , V . A . and S h a f f e r , C i B . E f f e c t o f v i t a m i n B l a n d y e a s t on t h e c a l o r i e s i n t a k e and w e i g h t b a l a n c e o f h y p e r t h y r o i d d o g s . E n d o c r i n o l o g y 3 1 , 567, 1942.  (19)  D r i l l , V.A. and Sherweod,C.R. E f f e c t o f v i t a m i n B l and t h e v i t a m i n B2 c o m p l e x on t h e w e i g h t , f o o d i n t a k e and e s t r u a l c y c l e o f hyperthyroid rats. •Amer. J o u r . P h y s i o l . 124, 6 8 3 , 1938.  (20.)  P r a z i e r , W . D . and R a v d i n , I . S . Use o f v i t a m i n B l i n t h e p r e - o p e r a t i v e of the h y p e r t h y r o i d p a t i e n t . S u r g e r y 4, 6 8 0 , 1938.  (21)  preparation  Gulick, Addison • The b a s a l m e t a b o l i s m o f n o r m a l immature w h i t e Amer. Jour.. P h y s i o l . 7 2 , 1 8 6 , 1925.  (22)  Hawk,P.B. and"" Bergeim^O. • " " Energy Metabolism. Chapter 25, P r a c t i c a l P h y s i o l o g i c a l Chemistry. ' | l t h * e d i t i o n . 1937' P. B l a k i s t o . n ' s 'Son & C o . , I n c . , P h i l a d e l p h i a .  (23)  H e r r i n g t o n , L.P. The h e a t r e g u l a t i o n o f s m a l l l a b o r a t o r y at various"environmental'temperatures. Amer. J o u r . P h y s i o l . 1 2 9 , 1 2 3 , 1940.  (24)  rats.  animals  H i m w i c k , H . E i , G o l d f a r b , W , "and C o w g I l l , G . R . The v i t a m i n B complex i n r e l a t i o n t o f o o d i n t a k e during hyperthyroidism. P r o c . S o c . E x p t l . B i o l . & Med. 2 8 , 646, 1 9 3 1 . :  68. (25)  H o r s t , K . , M e n d e l , L . B . and B e n e d i c t , F . G . The e f f e c t s o f some e x t e r n a l f a c t o r s u p o n t h e b a s a l m e t a b o l i s m Of t h e r a t . J . N u t . 7, 2 7 7 , 1934.  (26)  Jollife,N. Recent a d v a n c e s i n c l i n i c a l a p p l i c a t i o n s o f t h e B vitamins. J . Am. D i e t . A s s o c . 1 7 , 5, 1 9 4 1 .  (27)  K e s t n e r , 0. Uber d i e O b e r f l a c h e n r e g i l d e s S t o f f e n w e c h s e l s . P f l u g e r s A r c h . 2 3 4 , 2 9 0 , 1934.  (28)  KIIbank,S.C. . Factors i n Feeding a high p r o t e i n d i e t to Wistar Rats. Dept. o f Chemistry, U n i v e r s i t y of B r i t i s h Columbia, U n p u b l i s h e d t h e s i s , 1941  (29)  K i n g , ,'G.G. . Water s o l u b l e v i t a m i n s . A n n u a l R e v i e w o f B i o c h e m i s t r y 8, 3 7 1 , 1939.  (30)  Kingdon,C., B u n n e l l , I . L . and G r i f f i t h , Jr.,F.R. The f a s t i n g r e s p i r a t o r y m e t a b o l i s m o f t h e w h i t e r a t f o r 36 "hours f o l l o \ i y i h g c o n t r o l l e d f e e d i n g . Amer. J o u r . P h y s i o l . 137, 1 1 4 , 1942.  (31)  K l a u s , U*, and C l a r k , J . D . E f f e c t ' o f l a r g e amounts o f s i n g l e v i t a m i n s o f ' t h e B group"upon'rats"deficient'in other vitamins. Amer. J . Med. Sci© 2 0 4 , 3 6 4 , 1 9 4 2 . " •  (32)  K u b o , Ryuzo E f f e c t s o f ' c r y s t a l l i n e B l p r e p a r a t i o n on s u g a r metabolism. Tokyo I g a k k a i Z a s s i ( J . T o k y o Med. A s s o c . ) 5 4 , 5 3 , 1 9 4 0 .  (33)  Kunde, M..M. S t u d i e s on "metabolism. Amer. J o u r . P h y s i o l . 8 2 , 1 9 5 , 1927.  69. (54)  L u s k , G. A n i m a l C a l o r i m e t r y , 24. A n a l y s i s o f t h e o x i d a t i o n o f m i x t u r e s o f c a r b o h y d r a t e and f a t . A c o r r e c t i o n . J . B i o l . Chem. 59, 4 1 , 1924. ••  (35)  Namikawa, I t i r o The i n t e r r e l a t i o n s h i p s between v i t a m i n s and t h e t h y r o i d hormone f r o m t h e s t a n d p o i n t o f v i s c e r a l t i s s u e r e s p i r a t i o n and g l y c o l y s i s . I I I n t e r r e l a t i o n s h i p s b e t w e e n t h y r o x i n and v i t a m i n B l . Z l k k e r S y o k a k i kyogaku( E x p e r i m e n t a l G a s t r o e n t e r o l o g y ) 15, 355, 1940.  ( 3 6 ) .' S a l t e r ; ' W.T. . F l u c t u a t i o n s i n Body'Iodine. P h y s i o l . R e v . 2 0 , 359, 1940. (37)  Schwabe,E.L. and G r i f f i t h , J r . F.R. An e a s i l y c o n s t r u c t e d r a t m e t a b o l i s m a p p a r a t u s w h i c h a u t o m a t i c a l l y r e c o r d s oxygen c o n s u m p t i o n and a n i m a l ' a c t i v i t y . J . N u t . . 1 5 , 187, 1938.  (38)  Scrutinio, Luigi ; V i t a m i n B l and'the cure of h y p e r t h y r o i d i s m . D o l . Soc. I t a l . B i o l . s p e r . 14, 565, 1939.  (39)  Sherman,H.C. and Sandels,M.R. Further"experimental d i f f e r e n t i a t i o n of B ' and .&. ' ' • " " • - ' " . J . N u t . 3, 395, 1931.  vitamins  :  (40)  Sherman,C.C. and Sherman,H.C. The V i t a m i n s . '' • ' Ann. Rev. B i o c h e m . 6, 339,  1937.  (41)  S t a r r , P . and Pomerenze,H. Therapeutic studies i n hyperthyroidism. Ann. I n t e r n a l .Med. 15, 226, 1941.  (42)  Steinberg,C.BeR. U n t o w a r d e f f e c t s r e s u l t i n g f r o m t h e use doses of v i t a m i n B l . Am. J . D i g . D i s . 5, 680, 1938.  :  of l a r g e  70, (43)  S u p p l e e , G . C . , Bender,R.C. and Hanford,Z.M. I n t e r r e l a t e d v i t a m i n r e q u i r e m e n t s . The i n f l u e n c e o f t h i a m i n e , r i b o f l a v i n , p a n t o t h e n i c a c i d and v i t a m i n B6 o n " l i f r e r ' g l y c o g e n r e s e r v e s . J . Amer. Parm. A s s o c . 3 1 , 194, 1942.  (44)  Sure,B. The p r e s e n t s t a t u s o f v i t a m i n B2. The V i t a m i n s : A symposium o n . t h e p r e s e n t s t a t u s of t h e known .vitamins. Am. M d. A s s o c . 7 8 , 1932. e  (45)  S u r e , B . and Buchanan,K.S. A n t i t h y r o g e n i c a c t i o n of c r y s t a l l i n e B l . J . N u t . 1 3 , 513, 1937.  (46)  S u r e , B . and F o r d , J r . , Z . V i t a m i n I n t e r r e l a t i o n s h i p s : B l and B2 r e l a t i o n s h i p s "in metabolism. J . B i o l ; . Chem. 146, 2 4 1 , 1942.  (47)  S u r e , B . and' S m i t h , M.E. H y p e r t h y r o i d i s m and N u t r i t i o n . thyroxin. J . N u t . 7, 547, 1934.  inter•  I . V i t a m i n B and  (48)  S w i f t , R.W. and F o r b e s , R . M . ' ' The h e a t p r o d u c t i o n o f t h e f a s t i n g r a t i n ' r e l a t i o n t o the environmental temperature. J . N u t . 18, 307, 1939.  (49)  Sydenstricker,V.P.,Geeslin,L.E.,Templeton,C.M., Weaver,J.W. R i b o f l a v i n d e f i c i e n c y i n human s u b j e c t s . J . Am. Med. A s s o c . 1 1 3 , 1697, 1939.  ( 50) Wahl,H. The r e l a t i o n between v i t a m i n B 2 ( . r i b o f l a v i n ) the thyroid. K l i n . Y/ochschr. 18, 1363, 1939.  and  and  71. (51)  W e i g a n d , C . G . , E c k l e r , C . R . and Chen,K.K. A c t i o n and t o x i c i t y o f v i t a m i n B6 h y d r o c h l o r i d e , P r o c . S o c . E x p t l . B i o l & Med. 44, 147, 1940.  (52)  Wesson,L.G. The m e t a b o l i c r a t e and r e s p i r a t o r y q u o t i e n t o f r a t s f o l l o w i n g t h e i n g e s t i o n o f d e x t r i n and during fasting. J . Nut.. 3, 5 0 3 , 1 9 3 1 .  (53)  W i l l i a m s , R . R . and S p i e s , T . D . Vitamin B l ( Thiamine) a n d " i t s use i n medicine. New Y o r k , M a c m i l l a n , 1938.  

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