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The nutritional implications of lactose intolerance Tolensky, Arlene Frances 1975

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THE NUTRITIONAL IMPLICATIONS OF LACTOSE INTOLERANCE i-  *>y  \  ARLENE FRANCES TOLENSKY B.Sc,  McGill University,  1972  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS  FOR THE DEGREE OF  MASTER OF SCIENCE  i n the D i v i s i o n of Human N u t r i t i o n S c h o o l o f Home Economics  We accept t h i s t h e s i s as conforming  t o the  r e q u i r e d standard  The U n i v e r s i t y o f B r i t i s h Columbia December, 197^  In p r e s e n t i n g t h i s  thesis  an advanced degree at  further  agree  fulfilment  of  the  requirements  the U n i v e r s i t y of B r i t i s h Columbia, I agree  the L i b r a r y s h a l l make it I  in p a r t i a l  freely  available  for  t h a t p e r m i s s i o n f o r e x t e n s i v e copying o f  of  this  representatives. thesis for  It  financial  that  reference and study. this  thesis  f o r s c h o l a r l y purposes may be granted by the Head of my Department by h i s  for  or  i s understood that copying or p u b l i c a t i o n gain s h a l l  written permission.  Depa rtment The U n i v e r s i t y o f B r i t i s h Columbia Vancouver 8, Canada  not  be allowed without my  i  ABSTRACT  Adult  l a c t o s e i n t o l e r a n c e due t o low l a c t a s e l e v e l s  i s often associated with varying  degrees o f abdominal d i s t r e s s  r a n g i n g from b l o a t i n g and d i s t e n s i o n t o severe cramps and diarrhea.  Recent s t u d i e s have suggested t h a t these  i n t e s t i n a l disturbances of n u t r i e n t s  may i n t e r f e r e w i t h normal  i n addition to lactose.  gastro-  absorption  I n order t o i n v e s t i g a t e  t h i s p o s s i b i l i t y , both human and animal s t u d i e s were conducted. Twenty-three h e a l t h y C a u c a s i a n a d u l t s were used t o study the e f f e c t o f l a c t o s e on t h e a b s o r p t i o n a s c o r b i c a c i d and p r o t e i n .  of v i t a m i n A,  E i g h t o f the 2 3 s u b j e c t s were  l a c t o s e i n t o l e r a n t on the b a s i s o f a maximum r i s e o f blood glucose o f l e s s than  2 0 mg/100  ml over the f a s t i n g blood  g l u c o s e l e v e l a f t e r i n g e s t i o n o f 5 0 g o f l a c t o s e i n 3 0 0 ml water.  I n each study, blood samples were drawn a f t e r an f a s t and a t i n t e r v a l s up t o k hours a f t e r consuming  overnight  5 0 g l a c t o s e i n an aqueous s o l u t i o n or t e s t meal g e l a t i n , v i t a m i n C or v i t a m i n A.  containing  Sucrose r e p l a c e d  l a c t o s e as  a control. The  r e s u l t s from the human s t u d i e s f a i l e d t o demon-  s t r a t e t h a t l a c t o s e had an e f f e c t on the a b s o r p t i o n  of a s c o r b i c  a c i d , v i t a m i n A or p r o t e i n i n l a c t o s e i n t o l e r a n t s u b j e c t s . may be t h a t the composition of t h e t e s t d r i n k which  It  contained  f a t and p r o t e i n , may have a f f e c t e d the r a t e o f a b s o r p t i o n o f  the n u t r i e n t s t e s t e d through a delay  i n g a s t r i c emptying time.  However, the f i n d i n g t h a t a b s o r p t i o n  of v i t a m i n C remained  unaffected  even when consumed w i t h an aqueous s o l u t i o n of  l a c t o s e , i s a t t r i b u t e d to the p o s s i b i l i t y t h a t the l e v e l of a s c o r b i c a c i d g i v e n was  too low  t o show measurable d i f f e r e n c e s  i n blood l e v e l s of t h a t n u t r i e n t . To study the e f f e c t of l a c t o s e on the a b s o r p t i o n calcium,  f a t and  postweaning r a t s .  p r o t e i n , balance s t u d i e s were conducted The  the  using  experimental groups r e c e i v e d e i t h e r 10?S,  20fo or 3 0 $ l a c t o s e d i e t s , w h i l e an e q u i v a l e n t replaced  of  amount of sucrose  l a c t o s e i n the c o n t r o l d i e t s .  In a d d i t i o n , postweaning r a t s were g i v e n v i t a m i n A i n t r a g a s t r i c a l l y w i t h e i t h e r l a c t o s e or sucrose t o the e f f e c t of l a c t o s e on v i t a m i n A  investigate  absorption.  From the balance s t u d i e s w i t h r a t s , the r e s u l t s i n d i c a t e t h a t f e c a l n i t r o g e n and c a n t l y (p  <0,05)  However, f e c a l c a l c i u m  as  excretion  found t o be g e n e r a l l y lower f o r each l a c t o s e group r e l a t i v e  t o the c o n t r o l s , but the d i f f e r e n c e was cant  signifi-  h i g h e r i n a l l the animals f e d l a c t o s e  compared t o the c o n t r o l s . was  f a t e x c r e t i o n was  (p<0.05)  only a t the  Improved c a l c i u m  absorption  30$  may  l e v e l of l a c t o s e  signifi-  intake.  have important n u t r i t i o n a l  i m p l i c a t i o n s where d i e t a r y c a l c i u m though, t h a t the  statistically  intake  i s low.  I t appears  l e v e l of d i e t a r y l a c t o s e would most l i k e l y have  t o exceed the l i m i t s of normal l a c t o s e consumption t o have an e f f e c t on the a b s o r p t i o n  of n u t r i e n t s .  ACKNOWLEDGEMENT  I would l i k e t o thank my p a r e n t s f o r the l o v e , understanding and encouragement g i v e n me.  t h a t they have always  T h i s work i s d e d i c a t e d t o them.  I a l s o wish t o thank Dr. J . L e i c h t e r f o r h i s assistance  i n t h i s study, and Dr. M. Lee and Dr. J . A n g e l  f o r s e r v i n g on my committee.  iv. TABLE OF CONTENTS PAGE I . INTRODUCTION  1 k  I I . LITERATURE REVIEW A. A d u l t _ L a c t o s e _ I n t o l e r a n c e  4  1. D i a g n o s i s .  4  2. Pathogenesis  o f Symptoms  4  3. E t i o l o g y  5  a. G e n e t i c Theory.............  5  b. L a c t a s e I n d u c t i o n by M i l k Consumption  7  c. D i e t a r y I n h i b i t o r s . . . . ,  8  d. Disease H y p o t h e s i s .  8  B. T h e _ E f f e c t _ o f _ I n t e s t £&2$2§§-lGt:2i§ .§52§» •••••••••••••  9  1. The E f f e c t o f I n t e s t i n a l M o t i l i t y on N u t r i e n t Absorption.  9  r  2. The E f f e c t o f G a s t r i c Emptying,on N u t r i e n t Absorption • •  14  3. The E f f e c t o f D i e t Composition on Symptoms o f L a c t o s e I n t o l e r a n c e and N u t r i e n t A b s o r p t i o n . . . . . . 16 I I I . MATERIALS AND METHODS A. Human_Studies  19 •  1, E x p e r i m e n t a l Procedures.  19 20  a. The E f f e c t o f L a c t o s e on the A b s o r p t i o n o f P r o t e i n and V i t a m i n A  20  b. The E f f e c t o f Lactose on the A b s o r p t i o n o f Vitamins A and C  20  v. PAGE c. The E f f e c t o f Lactose on the A b s o r p t i o n of Vitamins A and C 2. Methods  21 22  a. Plasma Glucose D e t e r m i n a t i o n  22  b. Plasma Urea N i t r o g e n D e t e r m i n a t i o n . . . . . . . . . . . .  22  c. Plasma V i t a m i n A D e t e r m i n a t i o n . . . . .  23  d. Plasma V i t a m i n C D e t e r m i n a t i o n  23  3. S t a t i s t i c a l A n a l y s i s B. Animal_Studies  23 2k  1. E x p e r i m e n t a l Procedures. a. The E f f e c t o f L a c t o s e on the E x c r e t i o n o f Fat, N i t r o g e n and Calcium. b. The E f f e c t o f L a c t o s e on the A b s o r p t i o n o f Vitamin A 2. Methods  2^ 2k 26 27  a. N i t r o g e n D e t e r m i n a t i o n .  27  b. C a l c i u m D e t e r m i n a t i o n .  27  c. D e t e r m i n a t i o n o f F a t Content  27  d. Plasma V i t a m i n A D e t e r m i n a t i o n  27  3. S t a t i s t i c a l A n a l y s i s IV. RESULTS  27 29 29  A. Human_Studies 1. The E f f e c t o f Lactose on the A b s o r p t i o n o f Protein....  29  2. The E f f e c t o f Lactose on the A b s o r p t i o n o f Ascorbic Acid •  29  3. The E f f e c t Vitamin A  33  o f Lactose on the A b s o r p t i o n o f  vi. PAGE B. AnimalJ3tudies  33  1. The E f f e c t o f Lactose on the E x c r e t i o n o f F a t . N i t r o g e n and Calcium.  33  a. Body Weight Gain and Food Consumption  33  b. The E f f e c t o f L a c t o s e oh F e c a l F a t E x c r e t i o n . . . 35 c. The E f f e c t o f L a c t o s e on F e c a l and U r i n a r y Nitrogen Excretion  ,. 37  d. The E f f e c t o f Lactose on F e c a l and U r i n a r y Calcium E x c r e t i o n  37  2. The E f f e c t Vitamin A V.  of Lactose on the A b s o r p t i o n o f 41  DISCUSSION  45  A. HumanJStudies  4-5  B  • Animal J S t u d i e s  48  1. The E f f e c t o f Lactose on the E x c r e t i o n o f N i t r o g e n . F a t and C a l c i u m  48  2. The E f f e c t o f Lactose on t h e A b s o r p t i o n o f V i t a m i n A.  52  V I . RECOMMENDATIONS  53  VII. SUMMARY  55  BIBLIOGRAPHY  58  APPENDIX  70  vii. LIST OF TABLES PAGE I. II.  III.  IV,  V.  VI. VII.  Composition  of Diets  25  Mean Maximum R i s e + S.D. i n Plasma Urea i n Lactose T o l e r a n t and I n t o l e r a n t S u b j e c t s Given 5 5 g G e l a t i n and 2 5 , 0 0 0 IU V i t a m i n A With E i t h e r 5 0 g Lactose or 5 0 g Sucrose  30  Mean Maximum R i s e ± S.D. i n Plasma A s c o r b i c A c i d i n L a c t o s e T o l e r a n t and I n t o l e r a n t S u b j e c t s Given 5 0 0 mg V i t a m i n C and 2 5 , 0 0 0 IU v i t a m i n A w i t h E i t h e r 5 0 g Lactose or 5 0 g Sucrose  30  Mean Maximum R i s e ± S.D. i n Plasma A s c o r b i c A c i d i n Lactose I n t o l e r a n t S u b j e c t s G i v e n 2 0 0 , 0 0 0 IU V i t a m i n A and 1 g V i t a m i n G w i t h a T e s t Meal C o n t a i n i n g 1 5 g C a s i l a n , 2 5 ml O l i v e O i l and E i t h e r 4 5 g Lactose or 4 5 g Sucrose  32  Mean Maximum R i s e + S.D. i n Plasma V i t a m i n A i n L a c t o s e I n t o l e r a n t ~ S u b j e c t s Given 2 0 0 , 0 0 0 IU V i t a m i n A and 1 g V i t a m i n C w i t h a T e s t Meal C o n t a i n i n g 1 5 g C a s i l a n , 2 5 ml O l i v e O i l , and E i t h e r 4 5 g Lactose or 4 5 g Sucrose  32  Mean Weight Gain + S.D. of E x p e r i m e n t a l and C o n t r o l Animals Over a Ten Day P e r i o d ( N = 6 ) . . . . . . . . . .  34  Average Food Consumption + S.D. o f E x p e r i m e n t a l and C o n t r o l Animals Over a Ten Day P e r i o d (N=6).... 3 4  VIII.  E f f e c t of D i f f e r e n t Levels o f D i e t a r y Lactose on F e c a l E x c r e t i o n o f F a t (N=6)  36  IX.  E f f e c t of D i f f e r e n t Levels o f D i e t a r y Lactose on F e c a l E x c r e t i o n o f N i t r o g e n (N=*6)  38  E f f e c t o f D i f f e r e n t Levels of Dietary Lactose on U r i n a r y E x c r e t i o n o f N i t r o g e n (N=6)  39  E f f e c t o f D i f f e r e n t L e v e l s o f D i e t a r y L a c t o s e on F e c a l E x c r e t i o n o f C a l c i u m (N=6)  40  X. XI. XII. XIII.  E f f e c t o f D i f f e r e n t L e v e l s o f D i e t a r v Lactose on U r i n a r y E x c r e t i o n o f Calcium (N=6) Mean Plasma V i t a m i n A L e v e l s i n Postweaning Rats A f t e r I n t r a g a s t r i c A d m i n i s t r a t i o n o f 2 5 0 0 IU o f V i t a m i n A w i t h E i t h e r 5 0 0 mg Lactose or 5 0 0 mg Sucrose ( 4 animals p e r subgroup)  42  43  1.  I. INTRODUCTION Adult  l a c t o s e i n t o l e r a n c e due t o low l e v e l s o f  i n t e s t i n a l l a c t a s e a c t i v i t y i s common i n t h e m a j o r i t y throughout the world. races  I t i s p a r t i c u l a r l y evident  of adults  i n certain  and e t h n i c groups ( 1 ) , a f a c t t h a t accounts f o r i t s high  incidence  on a worldwide b a s i s .  Asians ( 8 - 1 5 ) , 21,28-29)i greater  I n Eskimos ( 2 , 3 ) ,  Jews  (4-7),  Negroes ( 1 6 - 2 7 ) and North American Indians ( 3 ,  the i n c i d e n c e  of lactose intolerance i s generally  than 7 0 $ and may even be as high as 90%.  On the other  hand, i n some peoples, i n c l u d i n g northwestern Europeans, the incidence  of lactose intolerance  i s o f t e n below 2 0 $ ( 1 ) .  In those i n d i v i d u a l s w i t h low l a c t a s e l e v e l s , sumption o f one or more g l a s s e s  of milk w i l l  induce  con-  various  degrees of abdominal d i s t r e s s r a n g i n g  from b l o a t i n g and d i s -  t e n s i o n t o severe cramps and d i a r r h e a  (30,31).  The symptom-  a t i c response o f a l a c t o s e i n t o l e r a n t i n d i v i d u a l i s a s s o c i a t e d w i t h t h e accumulation of l a c t o s e i n the i n t e s t i n a l lumen. Since  l a c t a s e l e v e l s are low, the a b i l i t y t o h y d r o l y z e  to i t s constituent  monosaccharides, glucose and g a l a c t o s e ,  which a r e r e a d i l y absorbed, i s reduced.  Consequently,  accumulates i n the lumen o f t h e s m a l l i n t e s t i n e c a u s i n g and  e l e c t r o l y t e changes which i n c r e a s e  In the c o l o n ,  lactose  lactose fluid  intestinal motility.  f e r m e n t a t i o n products r e s u l t i n g from b a c t e r i a l  a c t i o n on the unabsorbed l a c t o s e impair  absorption  l o a d and i n t e s t i n a l m o t i l i t y i s f u r t h e r enhanced.  o f the f l u i d Therefore,  the d i s t e n s i o n o f the s m a l l i n t e s t i n e and the i n c r e a s e d m o t i l i t y  2.  of both the s m a l l and abdominal d i s c o m f o r t  l a r g e i n t e s t i n e are r e s p o n s i b l e seen i n l a c t o s e  Although the  incidence  and  for  the  intolerance. the e t i o l o g y of a d u l t  l a c t o s e i n t o l e r a n c e have been i n v e s t i g a t e d e x t e n s i v e l y ,  little  i s known about the e f f e c t of l a c t o s e i n t o l e r a n c e  absorp-  t i o n o f n u t r i e n t s other than l a c t o s e . food  ant  Since r a p i d t r a n s i t  through the g a s t r o i n t e s t i n a l t r a c t may  time f o r the a b s o r p t i o n i n d i v i d u a l may  on the  of  not a f f o r d s u f f i c i e n t  of d i e t a r y n u t r i e n t s , a lactose  intoler-  not be d e r i v i n g f u l l n u t r i t i o n a l b e n e f i t s  when consuming only m i l k or other l a c t o s e - c o n t a i n i n g  products.  R e c e n t l y , Paige and Graham ( 3 2 ) noted t h a t l a c t o s e i n t o l e r a n t subjects  r e c e i v i n g a lactose-based  d i e t , showed an i n c r e a s e  in  s t o o l water, f a t and n i t r o g e n e x c r e t i o n as compared t o v a l u e s o b t a i n e d on a sucrose-based d i e t .  S i m i l a r l y , Calloway  Chenoweth ( 3 3 ) i n v e s t i g a t e d n u t r i e n t a b s o r p t i o n in lactose intolerant subjects. increased  and  and  retention  Their results indicated  f e c a l energy l o s s e s t h a t were l a c t o s e dose dependent  i n four i n t o l e r a n t subjects c o n t e n t over 1 2 day p e r i o d s , subjects.  each f e d d i e t s of v a r y i n g as compared to the two  lactose  control  Both s t u d i e s suggest t h a t consumption of m i l k or  other l a c t o s e - c o n t a i n i n g absorption  products might r e s u l t i n impaired ,  of n u t r i e n t s i n a d d i t i o n t o l a c t o s e . The  purpose of the p r e s e n t work was  t o examine the  e f f e c t of d i e t a r y l a c t o s e on n u t r i e n t a b s o r p t i o n  i n lactose  i n t o l e r a n t i n d i v i d u a l s as w e l l as i n postweaning r a t s , which have low  l e v e l s of i n t e s t i n a l l a c t a s e  activity.  3.  Human subjects were used to assess the e f f e c t of lactose on the absorption of vitamin A, ascorbic acid, and protein. Balance studies were c a r r i e d out using postweaning rats to examine the e f f e c t of lactose on the absorption of f a t , protein and calcium. In addition, postweaning r a t s were given vitamin A i n t r a g a s t r i c a l l y with either lactose or sucrose to investigate the e f f e c t of lactose on vitamin A absorption.  4.  I I . LITERATURE REVIEW A.  Adult_Lactose_Intolerance 1.  Diagnosis Intolerance  t o l a c t o s e has been found i n many a d u l t s  who were a b l e t o consume m i l k f r e e l y d u r i n g hood ( 5 D .  i n f a n c y and c h i l d -  Most a d u l t s who a r e l a c t o s e i n t o l e r a n t a r e a b l e t o  t o l e r a t e s m a l l q u a n t i t i e s o f milk, as i n c o f f e e or t e a . However, i n g e s t i o n o f one or more g l a s s e s  of milk  (30,31)  may  induce  symptoms r a n g i n g from f l a t u l e n c e and b l o a t i n g t o severe cramps and  diarrhea.  I n t e s t i n a l l a c t a s e a c t i v i t y as low as 7 u n i t s / g  p r o t e i n may be found i n an i n t o l e r a n t i n d i v i d u a l as compared t o approximately 7 0 u n i t s / g p r o t e i n i n a l a c t o s e t o l e r a n t (30,34).  Because o f the diminished  l e v e l s of l a c t a s e  subject activity  i n the i n t e s t i n a l brush border c e l l s , a l o a d o f l a c t o s e  will  not be s u f f i c i e n t l y h y d r o l y z e d t o i t s component u n i t s , g l u c o s e and  galactose.  C l i n i c a l l y , a f l a t l a c t o s e t o l e r a n c e curve i s  seen i n an i n t o l e r a n t s u b j e c t as i n d i c a t e d by a, r i s e o f b l o o d glucose o f l e s s than  2 0 mg/100  ml over the f a s t i n g blood  glucose l e v e l a f t e r a 5 0 g o r a l l a c t o s e load ( 3 5 ) .  T h i s low  r i s e i n blood g l u c o s e may be accompanied by g a s t r o i n t e s t i n a l symptoms.  2 . Pathogenesis of Symptoms The  symptoms a s s o c i a t e d w i t h low l a c t a s e l e v e l s a r e  caused by the accumulation o f l a c t o s e i n the i n t e s t i n a l lumen. The  unabsorbed l a c t o s e a t t r a c t s a net osmotic movement of water  5.  out  i n t o the lumen ( 3 6 ) .  of the s m a l l i n t e s t i n e ( 3 7 ) so  the sodium g r a d i e n t absorption  T h i s i s a s s o c i a t e d w i t h changes i n  o f water and  that  e l e c t r o l y t e s i s impaired.  Abdominal  d i s t e n s i o n and b l o a t i n g r e s u l t s c a u s i n g an a c c e l e r a t i o n i n t r a n s i t time  (37-39).  The  osmotic e f f e c t of the  disaccharide  i n the s m a l l i n t e s t i n e i s enhanced i n the  Here the l a c t o s e i s subjected  and  colon.  t o b a c t e r i a l d e g r a d a t i o n to a  number o f organic a c i d s , e s p e c i a l l y l a c t i c and (38-41).  accumulated  acetic acid  These are not w e l l absorbed i n the l a r g e i n t e s t i n e  i n t e r f e r e with absorption  the c o l o n ( 3 8 , 4 0 ) .  The  o f the f l u i d l o a d presented t o  symptoms seen then, are due  s i o n of the s m a l l i n t e s t i n e (42) and the both the s m a l l and f l u i d load ( 3 8 ) .  l a r g e i n t e s t i n e (42) Diarrhea  and  increased  to distenm o t i l i t y of  induced by the  increased  o c c a s i o n a l l y s t e a t o r r h e a may  be  F e c a l pH drops due  to  seen i n l a c t o s e i n t o l e r a n c e  (40,43-45).  the presence of the organic  a c i d s (46), b a c t e r i a l counts may  increased  (46), l a c t o s e as w e l l as glucose and g a l a c t o s e  may  found i n s t o o l s ( 4 7 ) .  3.  Etiology a. Genetic One  Theory  of the most w i d e l y accepted t h e o r i e s t o  the e t i o l o g y o f a d u l t l a c t o s e i n t o l e r a n c e i s the theory  (31).  explain  genetic  I t would account f o r the e q u a l l y h i g h  incidence  of l a c t o s e i n t o l e r a n c e i n those groups of people w i t h i n t h e i r n a t i v e environment and generations  those same peoples who  have l i v e d f o r  i n c o u n t r i e s of a t o t a l l y d i f f e r e n t environment  be be  than t h e i r n a t i v e l a n d . a high incidence  G i l a t et a l . (5)  f o r example, found  of l a c t o s e i n t o l e r a n c e among I s r a e l i Jews  i r r e s p e c t i v e of t h e i r o r i g i n , t h a t i s , Ashkenazi, Sephardi, Yemenite, I r a q i and there  Oriental.  i s also a high incidence  I t has  s i n c e been noted t h a t  of i n t o l e r a n c e among Canadian  and American Jews (6,7). I n v e s t i g a t i o n of the  f a m i l i a l incidence  i n t o l e r a n c e a l s o suggests a g e n e t i c intolerance  (8,40,48-51).  a l l members of two  of  lactose  e t i o l o g y of a d u l t  lactose  study, Neale (50)  In one  found t h a t  generations of a P a k i s t a n i f a m i l y  in Britain  e x h i b i t e d c l i n i c a l symptoms of l a c t o s e i n t o l e r a n c e and/or low  had  l e v e l s of i n t e s t i n a l l a c t a s e a c t i v i t y . Other workers (8,40,  48-49,51) have noted t h a t s u b j e c t s u s u a l l y had  a parent or s i b l i n g who  who  were l a c t o s e i n t o l e r a n t  had  experienced  intolerance  to lactose. In a d d i t i o n , Cook and  Kajubi  i n E a s t A f r i c a having a high i n c i d e n c e the  (23)  found a Bantu t r i b e  of l a c t o s e  "Hamitic" Hima and T u s s i t r i b e w i t h a low  Hutu and  I r u t r i b e s w i t h an intermediate  intolerance,  incidence  incidence  who  the  are  b e l i e v e d t o be of mixed Bantu/Hamitic o r i g i n .  These  suggest t h a t l a c t o s e i n t o l e r a n c e  origin.  i s of g e n e t i c  and  studies If this  i s so, then there should be no c o r r e l a t i o n between milk d r i n k i n g h a b i t s and  l e v e l s of l a c t a s e a c t i v i t y .  The  second hypothesis  c o n c e r n i n g the e t i o l o g y of l a c t o s e i n t o l e r a n c e d i s p u t e s assumption.  this  7.  b. Lactase I n d u c t i o n  by M i l k Consumption  T h i s theory s t a t e s t h a t the postweaning d e c l i n e i n l a c t a s e a c t i v i t y i n most mammals i s a normal consequence o f decreased m i l k consumption.  I f the enzyme i s a d a p t i v e , as t h i s  theory implies,  then v a r y i n g  the l a c t o s e c o n t e n t of the d i e t  should i n c r e a s e  i n t e s t i n a l lactase a c t i v i t y .  intolerant subjects, by g r a d u a l l y  In lactose  attempts a t i n d u c t i o n o f t h e l a c t a s e enzyme  i n c r e a s i n g the l a c t o s e c o n t e n t o f the d i e t have n o t  been s u c c e s s f u l  (52-56).  Conversely, i n healthy  d e n i a l of m i l k over a p e r i o d lactase a c t i v i t y  (57-58).  adult  o f time d i d not reduce  subjects,  intestinal  A c o r r e l a t i o n between the l e v e l s o f  i n t e s t i n a l l a c t a s e a c t i v i t y and m i l k d r i n k i n g h a b i t s has a l s o been d i f f i c u l t aptation  to establish (59,60-64).  I n man, t h e r e f o r e , ad-  o f i n t e s t i n a l l a c t a s e a c t i v i t y t o d i e t a r y l a c t o s e seems  u n l i k e l y as a c a u s a t i v e  factor i n adult lactose  Data from animal s t u d i e s  intolerance.  o f the a d a p t a t i o n o f  i n t e s t i n a l l a c t a s e however, have been c o n f l i c t i n g  ( 6 5 ) * A number  of workers have found t h a t l a c t a s e a c t i v i t y c o u l d be by  influenced  i n c r e a s i n g the l a c t o s e content o f the d i e t or by prolonged  lactose feeding  (66-75)«  Bolin et a l . (66-67)  demonstrated the  a d a p t i v e nature of i n t e s t i n a l l a c t a s e i n the a d u l t r a t , when an increase  i n l a c t a s e a c t i v i t y was produced a f t e r 5-8 weeks on  a 30% l a c t o s e d i e t ( 6 6 ) , as w e l l as on a 10% l a c t o s e d i e t ( 6 7 ) . However, the postweaning d e c l i n e be prevented by f e e d i n g (67).  i n l a c t a s e a c t i v i t y c o u l d not  a 10% l a c t o s e d i e t up t o 5 weeks o f age  Jones e t a l . ( 6 9 ) r e p o r t e d  s i g n i f i c a n t l y higher l e v e l s  of l a c t a s e i n 4 0 day o l d r a t s f e d a 6Q% l a c t o s e d i e t f o r one  8. to twelve weeks than i n r a t s fed glucose, sucrose or a l a b chow. A number of other i n v e s t i g a t o r s have obtained s i m i l a r r e s u l t s (70-74),  An  unsuccessful preventing  e q u a l l y l a r g e number of workers have been i n inducing  the s p e c i f i c a c t i v i t y  i t s d e c l i n e a f t e r weaning (76-80).  of l a c t a s e The  or  discrepancies  i n the f i n d i n g s are most l i k e l y due  t o d i f f e r e n c e s i n methodol-  ogy « l e n g t h of experimental p e r i o d ,  l e v e l of d i e t a r y  f e d , and  the  lactose  enzyme assay method used.  c. D i e t a r y  Inhibitors  Proponents of another theory to e x p l a i n the  etiology  of a d u l t l a c t o s e i n t o l e r a n c e , c l a i m t h a t c e r t a i n foods or drugs ingested  are l a c t a s e a n t a g o n i s t s  r e s u l t , l a c t o s e i n t o l e r a n c e may i n t e s t i n a l mucosa due  (82).  h a b i t s and  b e t e l nuts, may  which w i l l impair  a f f e c t lactase cause lactose  However, f u r t h e r s t u d i e s to i n v e s t i g a t e d i e t a r y drug usage of those r a c e s and  t i n g a high  a  A l t e r a t i o n s i n the  A l s o , drugs such as c o l c h i c i n e may  a decreased l a c t a s e p r o d u c t i o n absorption.  develop.  As  t o consumption of p a r t i c u l a r foods, f o r  example h i g h l y s p i c e d foods and activity  or i n h i b i t o r s (81).  incidence  e t h n i c groups e x h i b i -  of l a c t o s e i n t o l e r a n c e would determine  the v a l i d i t y of t h i s t h e o r y .  d. Disease Hypothesis T h i s theory suggests t h a t l a c t o s e i n t o l e r a n c e c e r t a i n population  groups may  in  be a secondary m a n i f e s t a t i o n  of  some s u b c l i n i c a l i n f e c t i o n indigenous to t h a t p a r t i c u l a r area.  9. In other words, where the high,  incidence  of l a c t o s e i n t o l e r a n c e i s  f o r example i n t r o p i c a l c o u n t r i e s ,  and/or m a l n u t r i t i o n i t s enzymes and  (85-86) may  thus impair  i n f e c t i o n (83-84)  a l t e r the  i t s absorptive  i n t e s t i n a l mucosa capacity.  and  Bowie  e t a l . (87-89) have attempted to l i n k kwashiorkor i n A f r i c a n c h i l d r e n to adult lactose intolerance. l a c t a s e l e v e l s may  They suggest t h a t  low  r e s u l t from i n t e s t i n a l mucosa damage due  p r o t e i n deprivation i n childhood. Bowie's s t u d i e s may  to  However, the c h i l d r e n i n  have been l a c t o s e i n t o l e r a n t independent  of the kwashiorkor, t h a t is, b e f o r e i t s onset. work with r a t s r e v e a l e d  In a d d i t i o n ,  t h a t p r o t e i n d e p r i v a t i o n d i d not a f f e c t  i n t e s t i n a l l a c t a s e l e v e l s (90-91). I t appears t h a t no s i n g l e theory may  account f o r the  marked d i f f e r e n c e s i n the occurence of a d u l t l a c t o s e  intolerance  i n various population  intolerance  groups.  i s probably a manifestation l a c t a s e l e v e l s i n the  of g e n e t i c  intestine.  c e r t a i n foods have damaged the may  Primary a d u l t l a c t o s e  factors influencing  Where d i s e a s e  and/or drugs or  i n t e s t i n a l mucosa, l a c t a s e l e v e l s  a l s o be a f f e c t e d r e s u l t i n g i n another, secondary type of  adult lactose  B.  intolerance.  The_Effect_of_Intestim  1. The  E f f e c t of I n t e s t i n a l M o t i l i t y ori N u t r i e n t  Absorption The responsible  parasympathetic nervous system i s l a r g e l y  f o r normal g a s t r o i n t e s t i n a l f u n c t i o n (92,93).  10. Vagal s t i m u l a t i o n o f the c h o l i n e r g i c f i b e r s t h a t are p r e s e n t w i t h i n the i n t e s t i n a l w a l l tends t o i n c r e a s e the o v e r a l l degree of a c t i v i t y by promoting p e r i s t a l s i s o f the i n t e s t i n a l D i s t e n s i o n , presence o f food or s p e c i f i c chemical  tract.  substances  can s t i m u l a t e the nerve endings and extreme i r r i t a t i o n can elicit  the " p e r i s t a l t i c r u s h " .  T h i s begins  i n the duodenum and  passes down the e n t i r e l e n g t h of s m a l l i n t e s t i n e t o the i l e o c e c a l v a l v e i n a matter o f minutes. i n t e s t i n e i s r e l i e v e d of excessive i t s contents  I n t h i s way, the s m a l l i r r i t a t i o n or d i s t e n s i o n as  a r e swept i n t o the c o l o n .  On the other hand, s t r o n g  s t i m u l a t i o n o f the sympathetic nerve supply can t o t a l l y movement o f food through the g a s t r o i n t e s t i n a l t r a c t .  block The e f f e c t  of e i t h e r extreme o f i n t e s t i n a l m o t i l i t y on n u t r i e n t a b s o r p t i o n i s d i s c u s s e d below. C l i n i c a l as w e l l as experimental  i n v e s t i g a t i o n s have  r e v e a l e d t h a t t r a n s i t time through the s m a l l i n t e s t i n e i s a c r i t i c a l f a c t o r i n optimal n u t r i e n t a b s o r p t i o n (9**—108).  In  1936, Wade (94) f i r s t noted the r e l a t i o n s h i p between m o t i l i t y and a b s o r p t i o n .  He suggested t h a t normal g a s t r o i n t e s t i n a l  a b s o r p t i o n i s dependent upon normal g a s t r o i n t e s t i n a l m o t i l i t y . In h i s treatment o f two c e l i a c c h i l d r e n , he a d m i n i s t e r e d  a  p e r i s t a l t i c s t i m u l a n t t o c o r r e c t the reduced m o t i l i t y o f the i n t e s t i n a l t r a c t and t o cause a p e r i o d o f more r a p i d a b s o r p t i o n of t h e chyme from the lumen.  The r e s u l t was an i n c r e a s e i n  body weight and h e i g h t , the e l e v a t i o n o f p r e v i o u s l y f l a t glucose t o l e r a n c e curves and the eventual, r e t u r n t o normal intestinal peristalsis.  I n 19^0, May and McCreary (95)  11.  conducted an experiment to prove t h a t low blood sugar i n c e l i a c disease was tine.  i n f a c t r e l a t e d t o h y p o m o t i l i t y of the s m a l l  They found a d e f i n i t e improvement i n glucose  curves where a p e r i s t a l t i c s t i m u l a n t had been i n t r a d u o d e n a l l y w i t h the glucose  load.  The  intes-  tolerance  administered  authors  concluded  t h a t the e f f i c i e n c y of a b s o r p t i o n depends upon i n t i m a t e c o n t a c t of the mucosa w i t h the i n t e s t i n a l contents accomplished by the constant tine.  Therefore,  and t h a t t h i s may  segmenting a c t i v i t y of the  they suggest t h a t e i t h e r a  be  intes-  decrease,or  i n c r e a s e i n p e r i s t a l t i c a c t i v i t y would l i k e l y r e s u l t  in a  reduction i n nutrient absorption. Subsequent s t u d i e s have s i n c e confirmed  that altered  i n t e s t i n a l m o t i l i t y , whether drug- or d i s e a s e - i n d u c e d , a d i r e c t r o l e i n the malabsorption 102,105-107).  vitamin A (102)  (96),  of c e r t a i n n u t r i e n t s  Where h y p o m o t i l i t y has been induced  t r a t i o n of a p e r i s t a l t i c 2  inhibitor  ^ s o d i u m and water  plays  have been found to be impaired.  adminis-  absorption  (96-102) (97-98),  by  and  due  (100).  to the experimental  The  c o n f l i c t i n g r e s u l t s are  procedure used t o study  a slow i n t r a d u o d e n a l  substance had been used.  a c t i v i t y of the duodenum was  absorption.  (99il01)  although  (99»101)  probably  or enhanced  i n f u s i o n procedure of the  Therefore,  man)  However, i n other  Where a b s o r p t i o n seemed to be u n a f f e c t e d (100),  of  fat (in  s t u d i e s , a b s o r p t i o n appeared to be at l e a s t u n a f f e c t e d or even improved  (96-98,  test  the segmenting  reduced, the q u a n t i t y of p e r f u s a t e  a v a i l a b l e to the mucosal s u r f a c e per u n i t o f time was c i e n t l y s m a l l t o a l l o w a b s o r p t i o n t o proceed  normally.  suffi-  12. Conversely,  where n u t r i e n t a b s o r p t i o n was  (96-98,102),  impaired  the t e s t s o l u t i o n had been i n j e c t e d d i r e d t l y i n t o the duodenum and  l i k e the c l i n i c a l s t a t e of h y p o m o t i l i t y  (celiac  disease),  the l o a d t o the mucosal s u r f a c e exceeded i t s p e r i s t a l t i c capacity.  I t appears then t h a t a b s o r p t i o n  i s i n f a c t reduced  where i n t e s t i n a l m o t i l i t y i s decreased. The  r e p o r t s concerning  the e f f e c t of h y p e r m o t i l i t y  on n u t r i e n t a b s o r p t i o n have a l s o been c o n f l i c t i n g Reduced a b s o r p t i o n  of glucose  (104),  (102-108).  f a t (102,105), and  water,  sodium and c h l o r i d e (106-10?), have been c i t e d i n drug- or hormone-induced i n t e s t i n a l h y p e r m o t i l i t y i n man S i m i l a r s t u d i e s have obtained mentioned above (99.103.108).  and  animals.  c o n t r a d i c t o r y r e s u l t s t o those T h i s may  be due  i n the i n t e s t i n a l segment chosen f o r study. i n c r e a s e i n n u t r i e n t a b s o r p t i o n may  to d i f f e r e n c e s  An  r e f l e c t the  apparent absorptive  a c t i v i t y of t h a t p a r t i c u l a r segment of the i n t e s t i n e .  In f a c t ,  the t o t a l amount of m a t e r i a l absorbed per u n i t of time, r a t h e r than per u n i t of l e n g t h , may  have a c t u a l l y been decreased.  C l i n i c a l i n v e s t i g a t i o n s of absorption hypermotile  s t a t e , such as i n t h y r o t o x i c o s i s and  sucrose-isomaltose  malabsorption  (104).  congenital  syndrome, i n d i c a t e t h a t  a b s o r p t i o n of n u t r i e n t s i s reduced. hyperthyroidism  i n a "natural"  Steatorrhea  i s common i n  L a u n i a l a (37-38) has r e p o r t e d  decrease i n p a l m i t a t e , x y l o s e and a r g i n i n e a b s o r p t i o n c h i l d with congenital sucrose-isomaltose  malabsorption.  a in a The  accumulation of l a c t o s e i n the i n t e s t i n a l lumen of l a c t o s e  13. i n t o l e r a n t i n d i v i d u a l s may  be c o n s i d e r e d  analogous to  s u c r o s e - i s o m a l t o s e m a l a b s o r p t i o n seen i n CSIM. t h a t the  lactose-induced  ance might be  I t follows  hypermotile s t a t e i n l a c t o s e  i n t e r f e r i n g with absorption  i n a d d i t i o n to l a c t o s e .  of d i e t a r y  Paige and Graham (32)  between 22 months and  then,  intolernutrients  recently  conducted a balance study u s i n g f o u r i n t o l e r a n t and subjects  the  6 years of age.  two  tolerant  They noted  that  the l a c t o s e i n t o l e r a n t c h i l d r e n r e c e i v i n g a l a c t o s e - c a s e i n d i e t d i d not r e t a i n n u t r i e n t s as w e l l as they d i d on a diet.  Their findings  include*  a) a decrease i n apparent n i t r o g e n a b s o r p t i o n of  sucrose-casein  from 93%  to  83%  intake  b) a r e d u c t i o n  i n n i t r o g e n r e t e n t i o n from 15% t o 5% of  c) a decrease i n f a t a b s o r p t i o n  as i n d i c a t e d by an  intake  elevation  i n s t o o l f a t from 3 g/day to 5 g/day d) an i n c r e a s e  i n s t o o l weight from a mean of 38 g/day t o  147  g/day. Nutrient  absorption  d i d not appear to be a f f e c t e d by  d i e t f o r the t o l e r a n t s u b j e c t s .  A c c o r d i n g t o these r e s u l t s , i t  appears t h a t l a c t o s e i n t o l e r a n t s u b j e c t s f e c a l l o s s e s of n u t r i e n t s  Four i n t o l e r a n t and  two  may  be  i n a d d i t i o n to lactose  Calloway and Chenoweth (33)  sustaining itself,  have a l s o examined t h i s p o s s i b i l i t y .  t o l e r a n t s u b j e c t s were c o n f i n e d  metabolic ward f o r 48 days d u r i n g which each s u b j e c t each of 4 d i e t s f o r twelve day a) 1000  g of homogenized low-fat  per day,  supplying  either  periods.  The  to a  received  diets consisted  m i l k d i v i d e d i n t o four meals  a t o t a l of 5 0 g l a c t o s e  ofs  14. b) 1000 g o f m o d i f i e d  low-fat  milk e n z y m a t i c a l l y  processed so  as t o reduce l a c t o s e content by approximately 50% c) 1000 g s i m u l a t e d  l o w - f a t milk w i t h glucose and g a l a c t o s e  instead of lactose d) wheaten foods only because they a f f e c t n u t r i e n t regardless  of i n t e s t i n a l lactase  absorption  levels.  Calloway and Chenoweth (33) found t h a t two o f the i n t o l e r a n t s u b j e c t s had i n c r e a s e d hydrogen l e v e l s i n the breath higher  as w e l l as  f e c a l l o s s e s o f moisture, dry s o l i d s and energy, t h a t  were l a c t o s e dose dependent.  These r e s u l t s concur w i t h those  of Paige and Graham ( 3 2 ) , t h a t l a c t o s e f e e d i n g may l e a d t o n u t r i t i o n a l l y s i g n i f i c a n t f e c a l losses of nutrients i n subjects w i t h low l a c t a s e  levels.  I t should be noted t h a t a l l these s t u d i e s have purposefully eliminated  the e f f e c t o f g a s t r i c emptying time.in order  to examine the e f f e c t o f i n t e s t i n a l m o t i l i t y alone on n u t r i e n t absorption.  Under normal c o n d i t i o n s , g a s t r i c emptying  time i n  a d d i t i o n t o the p e r i s t a l t i c a c t i v i t y o f the s m a l l i n t e s t i n e determine the r a t e o f i n t e s t i n a l a b s o r p t i o n  2.  (109-113).  The E f f e c t o f G a s t r i c Emptying on N u t r i e n t  Absorption  1  The  volume o f g a s t r i c c o n t e n t s t r a n s f e r r e d t o the  duodenum i s g e n e r a l l y under the and  i n h i b i t o r y influence of neural  hormonal f a c t o r s o r i g i n a t i n g i n the duodenum (92,109,111).  In d e c r e a s i n g  order  o f potency» f a t t y a c i d s , f a t s ,  peptones, amino a c i d s , sugars, other and  low pH p r e s e n t  proteoses,  starch digestion  i n the duodenum w i l l s t i m u l a t e the  products, intra-  15. muscular p l e x i to t r a n s m i t the e n t e r o g a s t r i c r e f l e x to stomach and consequently  i n h i b i t g a s t r i c evacuation.  the For  example, the g r e a t e r the c o n c e n t r a t i o n of s o l u t e s i n the i n t e s t i n e , the s t r o n g e r w i l l be the e x c i t a t i o n of the and  small  receptors  the s m a l l e r the volume of m a t e r i a l pumped from the stomach  i n t o the duodenum.  The  presence of f a t i n the s m a l l  w i l l a l s o delay g a s t r i c emptying v i a a hormone s y n t h e s i z e d , i n the i n t e s t i n a l w a l l .  intestine  (enterogastrone)  G a s t r i c d i s t e n s i o n alone  w i l l a c c e l e r a t e the r a t e of g a s t r i c emptying.  I t i s not  s u r p r i s i n g t h e r e f o r e , t h a t l a r g e d e v i a t i o n s i n the r a t e o f t h i s t r a n s f e r would i n f l u e n c e n u t r i e n t a b s o r p t i o n e s p e c i a l l y where the a b s o r p t i v e c a p a c i t y of the mucosa o f the s m a l l i n t e s t i n e i s impaired  i n some  way.  S t u d i e s have shown t h a t a decrease i n the r a t e of t r a n s f e r of g a s t r i c contents  i n h e a l t h y animals r e s u l t s i n a  reduced r a t e of n u t r i e n t a b s o r p t i o n (114-116).  An  increase i n  the volume of g a s t r i c contents pumped per minute i n t o the duodenum r e s u l t s i n decreased  n u t r i e n t a b s o r p t i o n only where  the a b s o r p t i v e c a p a c i t y of the s m a l l i n t e s t i n e i s impaired For example where l a c t a s e l e v e l s are low, r a t e of g a s t r i c emptying w i l l of n u t r i e n t s (118-120). presented  (117).  an a c c e l e r a t i o n i n the  lead to a reduction i n absorption  In other words, the l a c t o s e l o a d  t o the i n t e s t i n e w i l l exceed the c a p a c i t y of the  i n t e s t i n a l l a c t a s e l e v e l s to c l e a v e the l a c t o s e molecule i t s a b s o r p t i o n w i l l be impaired. g a s t r i c emptying time i n these absorption process.  and  Consequently, a delay i n  i n d i v i d u a l s i s b e n e f i c i a l to the  In t h e i r study  of c a l c i u m a b s o r p t i o n i n  16.  l a c t o s e i n t o l e r a n t i n d i v i d u a l s , Kocian e t a l . ( 1 2 1 ) n o t e i The slower supply o f chyme p r o t e c t s the s m a l l i n t e s t i n e a g a i n s t l a c t o s e o v e r l o a d i n g although the l a c t a s e a c t i v i t y o f the i n t e s t i n a l e p i t h e l i u m i s r e l a t i v e l y low and thus renders a b e t t e r u t i l i z a t i o n of c a l c i u m p o s s i b l e . The slower supply o f c a l c i u m reduces the amount o f f e r e d p e r u n i t o f time and thus a l s o increases the percentage o f absorbed c a l c i u m . T h e r e f o r e , i f a b s o r p t i o n i s improved emptying  through a d e l a y i n g a s t r i c  time, the abdominal d i s t r e s s symptoms a s s o c i a t e d w i t h  l a c t o s e i n t o l e r a n c e may be m o d i f i e d t o o , t o some e x t e n t . The r e l a t i o n s h i p of d i e t a r y m o d i f i c a t i o n o f g a s t r i c emptying and the appearance  of c l i n i c a l symptoms of l a c t o s e  time  intolerance  i s d i s c u s s e d i n the p r o c e e d i n g s e c t i o n .  3« The E f f e c t o f D i e t Composition on Symptoms o f Lactose I n t o l e r a n c e and N u t r i e n t A b s o r p t i o n The symptomatic response o f a l a c t o s e  intolerant  i n d i v i d u a l depends on the composition o f the meal i n which the lactose i s given.  A number o f workers  (122-127)?'  have shown  t h a t the f a t and/or p r o t e i n content o f a meal or even the m i l k i t s e l f , may reduce the abdominal d i s c o m f o r t individual.  o f an i n t o l e r a n t  Bayless and Paige ( 1 2 3 ) note t h a t m i l k consumed  alone seems t o induce g r e a t e r abdominal taken w i t h a meal.  d i s c o m f o r t than i f  They suggest t h a t t h e d i f f e r e n t components  of a meal may d e l a y g a s t r i c emptying  time.  I n t h i s way the low  l e v e l o f i n t e s t i n a l l a c t a s e i s not "overloaded" w i t h l a c t o s e and f l u i d and e l e c t r o l y t e balance i s not d i s t u r b e d .  Normal  p e r i s t a l s i s can be maintained, thus a v o i d i n g or a t l e a s t r e d u c i n g the symptomatic response t h a t would otherwise be seen in lactose  intolerance.  17.  Other i n v e s t i g a t o r s have shown ( 1 2 4 - 1 2 6 ) composition  of the milk i t s e l f may  that  be s u f f i c i e n t to modify  symptoms of l a c t o s e i n t o l e r a n c e a l s o through a delay emptying time.  In one  study ( 1 2 5 ) »  the  in gastric  symptomatic responses of 8  i n t o l e r a n t s u b j e c t s were compared a f t e r r e c e i v i n g 5 0 0 ml  skim  milk and a f t e r r e c e i v i n g an e q u i v a l e n t amount of whole m i l k . Less d i s c o m f o r t consumed. m i l k may  was  experienced  Therefore,  a f t e r the whole m i l k  the f a t and p r o t e i n l e v e l s of a meal or  a l l e v i a t e the symptoms of l a c t o s e i n t o l e r a n c e by  d e l a y i n g g a s t r i c emptying time and r e d u c i n g (124). less  was  intestinal motility  Whether or not n u t r i e n t a b s o r p t i o n remains impaired  is  evident. K o c i a n e t a l . ( 1 2 1 ) suggest t h a t where low  l e v e l s are p r e s e n t , l a c t o s e l o a d may  a d e l a y i n g a s t r i c emptying time a f t e r a  be important f o r a b s o r p t i o n t o occur  However, L e i e h t e r ( 1 2 5 ) showed t h a t although the response was  lactase  l e s s i n t e n s e , the r i s e  symptomatic  i n blood glucose  improve i n l a c t o s e i n t o l e r a n t i n d i v i d u a l s who  properly.  d i d not  r e c e i v e d whole  m i l k as compared t o skim or an aqueous l a c t o s e s o l u t i o n . should be noted though, t h a t the whole m i l k may t i v e l y delayed  L  It  have e f f e c -  g a s t r i c emptying so as to reduce the r a t e of  lactose absorption,  and  e v e n t u a l l y i n c r e a s e the  q u a n t i t y of l a c t o s e absorbed.  absolute  T h i s might have been e v i d e n t  had a b s o r p t i o n been f o l l o w e d f o r a longer p e r i o d than the time of the l a c t o s e t o l e r a n c e t e s t which l a s t e d only one Paige et a l . (127)  hour.  found t h a t f e e d i n g lower l e v e l s  of l a c t o s e t o i n t o l e r a n t s u b j e c t s was  also effective i n  18. reducing  t h e i r symptomatic response, however, l a c t o s e  curves s t i l l  d i d not  improve.  Bedine and  B a y l e s s (128)  s t r a t e d t h a t i n l a c t o s e i n t o l e r a n t s u b j e c t s who a t i c , as l i t t l e s o l u t i o n (21.7 net  f l u i d and  as 3 and  $ g of l a c t o s e i n 2G0  sodium/1, 3 7 . 1 mEq  mEq  demon-  were asymptomml of e l e c t r o l y t e  potassium/1),; r e s u l t e d i n  sodium accumulation i n the s m a l l i n t e s t i n e .  From these s t u d i e s , i t appears t h a t the l e v e l s of a meal or m i l k itself  tolerance  (127-130),  may  (123-126),  f a t and  or the l a c t o s e content  be a l t e r e d so as t o a l l e v i a t e the  of l a c t o s e i n t o l e r a n c e .  protein  symptoms  However, i t i s s t i l l not c l e a r whether  or not n u t r i e n t a b s o r p t i o n  i s concurrently  improved.  On  the  other hand, s t u d i e s of the e f f e c t of a l t e r e d i n t e s t i n a l m o t i l i t y on n u t r i e n t a b s o r p t i o n  ( S e c t i o n I I . B . l ) suggest t h a t  the  symptomatic response induced when l a c t o s e i s consumed alone i n t e r f e r e with absorption The  of n u t r i e n t s i n a d d i t i o n to l a c t o s e .  p r e s e n t work i s concerned w i t h i n v e s t i g a t i o n of t h i s  possibility1  t h a t the l a c t o s e - i n d u c e d  a l a c t o s e i n t o l e r a n t i n d i v i d u a l may for  absorption  l a c t a s e l e v e l s may  afford sufficient  Consequently,  products.  in  time  an  not be d e r i v i n g f u l l  t i o n a l b e n e f i t s when consuming only m i l k or other ing  latter  state of,hypermotility  not  of d i e t a r y n u t r i e n t s ,  i n d i v i d u a l w i t h low  may  nutri-  lactose-contain-  19.  I I I . MATERIALS AND  METHODS  A. Huraan_Studies In order t o study the e f f e c t o f l a c t o s e on  the  a b s o r p t i o n o f v i t a m i n A, a s c o r b i c a c i d and p r o t e i n , twentythree r e s i d e n t s o f Vancouver, B r i t i s h Columbia were used.  All  nine females between 2 1 and 3 1 years of  age,  were Caucasians}  mean = 2 5 years, f o u r t e e n males between 2 2 and 3 3 years, mean = 28 years.  Each s u b j e c t was  questioned  about h i s g e n e r a l  p h y s i c a l c o n d i t i o n and on t h i s b a s i s was healthy.  c o n s i d e r e d t o be  None r e p o r t e d a f a m i l y h i s t o r y of d i a b e t e s . F o l l o w i n g an o v e r n i g h t f a s t , each s u b j e c t r e c e i v e d  a lactose tolerance test.  Venous b l o o d samples were drawn  w h i l e the s u b j e c t s were f a s t i n g and a t 1 5 , 3 0 and 6 0 minute i n t e r v a l s a f t e r o r a l i n g e s t i o n of 5 0 g l a c t o s e 3 0 0 ml water.  1  Development of any symptoms such as  b l o a t i n g , gas, cramps or d i a r r h e a were r e c o r d e d . r i s e i n b l o o d glucose  of l e s s than  20  i n t e s t i n a l symptoms were c o n s i d e r e d intolerance.  dissolved i n  mg/100  flatulence, A maximum  ml and  gastro-  i n d i c a t i v e of lactose  On t h i s b a s i s , e i g h t o f the s u b j e c t s were l a c t o s e  i n t o l e r a n t , and the remaining  f i f t e e n were t o l e r a n t .  The n u t r i e n t s chosen f o r study were based on the following considerations! a) the d r i n k or meal should be a c c e p t a b l e t o the s u b j e c t s  1)  ffC-lactose,  Fisher Scientific,  N.J.  20. b) peak a b s o r p t i o n of the n u t r i e n t should occur w i t h i n a f o u r hour p e r i o d c) a b s o r p t i o n of the n u t r i e n t should not be a f f e c t e d by other n u t r i e n t s present  the  i n the t e s t s o l u t i o n  d) a b s o r p t i o n of the n u t r i e n t should vary p r o p o r t i o n a l l y w i t h the q u a n t i t y I t was  decided  ingested. t h a t v i t a m i n s A and C seemed t o meet the above  considerations.  G e l a t i n ;was  a l s o g i v e n i n order to measure  changes i n b l o o d urea l e v e l s as an i n d i c a t o r of p r o t e i n absorption ( 1 3 D .  The  l e v e l s of v i t a m i n s A and C and p r o t e i n  i n g e s t e d and the time i n t e r v a l s a t which blood samples were drawn were based on s t u d i e s r e p o r t e d The  t o l e r a n t and  i n the l i t e r a t u r e  (132).  i n t o l e r a n t s u b j e c t s served as their,own  c o n t r o l s . , Sucrose r e p l a c e d the l a c t o s e i n the c o n t r o l s t u d i e s .  1 . Experimental  Procedures  a. The E f f e c t o f Lactose and V i t a m i n A  on the A b s o r p t i o n ' o f  Protein  In order t o study the e f f e c t of l a c t o s e on p r o t e i n and v i t a m i n A a b s o r p t i o n , a p r e l i m i n a r y study u s i n g 5 t o l e r a n t and 8 i n t o l e r a n t s u b j e c t s was  c a r r i e d out.  A f t e r an  overnight  f a s t , venous blood samples were drawn, w h i l e the s u b j e c t s were still  f a s t i n g and a t 6 0 , 1 2 0 , 180  a f t e r i n g e s t i o n of a t e s t d r i n k . l a c t o s e and  55 g gelatin  1  and  240 minute  The  d r i n k c o n s i s t e d o f 50 g  d i s s o l v e d i n 400  same time each s u b j e c t i n g e s t e d  25»000  intervals  ml water. 2  IU v i t a m i n A  At  the  i n capsule  form. 1 ) Knox u n f l a v o r e d g e l a t i n , Knox Foods, Trenton, O n t a r i o . 2) 2 5 , 0 0 0 IU v i t a m i n A/capsule, S t a n l e y Drug Products L t d . , Vancouver, B.C.  21. The  f o l l o w i n g week, the procedure was repeated w i t h the same  s u b j e c t s except t h a t 50 g sucrose r e p l a c e d the l a c t o s e i n the test drink.  The v o l u n t e e r s were i n s t r u c t e d t o consume the  f l u i d as q u i c k l y as p o s s i b l e because the g e l a t i n had a tendency to congeal.  b. The E f f e c t of Lactose on the A b s o r p t i o n o f Vitamins A and C Another p r e l i m i n a r y experiment  involving 9 subjects,  3 i n t o l e r a n t and 6 t o l e r a n t , was conducted  t o f o l l o w the e f f e c t  of l a c t o s e (without g e l a t i n ) on the a b s o r p t i o n on v i t a m i n s A and C.  The procedure  was s i m i l a r t o the f i r s t  experiment  except t h a t each s u b j e c t i n g e s t e d 50 g l a c t o s e d i s s o l v e d i n 400 ml water w i t h 500 mg v i t a m i n C IU v i t a m i n A i n capsule form.  1  i n t a b l e t form and 25.000  Blood samples were drawn while  the s u b j e c t s were f a s t i n g and a t 60, 120, 180 and 240 minute i n t e r v a l s a f t e r i n g e s t i o n o f the t e s t d r i n k .  T h i s was  repeated the f o l l o w i n g week with sucrose i n s t e a d of l a c t o s e .  c. The E f f e c t of Lactose on the A b s o r p t i o n o f Vitamins A and C S i n c e v i t a m i n A i s f a t s o l u b l e , i t was decided t o give our s u b j e c t s the v i t a m i n w i t h a t e s t meal, r a t h e r than a d r i n k , t o study the e f f e c t of l a c t o s e on i t s a b s o r p t i o n . The meal, adopted  from Barrowman et/;sPl). (133-) c o n t a i n e d 45 g l a c t o s e ,  1) 500 mg v i t a m i n C/ tablet,;, S t a n l e y Drug Products, Vancouver, B.C.  22. 15  g casilan  1  and  25  ml o l i v e o i l as w e l l as  200,000  IU v i t a m i n  2  A  i n c a p s u l e form.  Each s u b j e c t a l s o r e c e i v e d 1 g v i t a m i n C  because the p r e v i o u s dose of 5 0 0 mg was thought  t o be too low  t o show measurable d i f f e r e n c e s i n blood v i t a m i n C l e v e l s . Venous b l o o d samples were drawn a f t e r an o v e r n i g h t f a s t and a t 90,  180 and 240 minute i n t e r v a l s a f t e r i n g e s t i o n o f the meal.  At a l a t e r date these same s u b j e c t s r e c e i v e d a s i m i l a r meal except sucrose r e p l a c e d the l a c t o s e . 2.  Methods a. Plasma Glucose  Determination  Blood samples were drawn and t r a n s f e r r e d t o t e s t tubes c o n t a i n i n g potassium  oxalate, centrifuged at  f o r 2 0 minutes and plasma was removed and f r o z e n . was determined  2000  RPM  The g l u c o s e  w i t h i n a few days by the glucose oxidase method  (134).  b. Plasma Urea N i t r o g e n D e t e r m i n a t i o n Blood samples were drawn and t r a n s f e r r e d t o h e p a r i n i z e d t e s t tubes and t r e a t e d as above. l e v e l s were determined (135.),.-  Plasma urea n i t r o g e f r  a c c o r d i n g t o Hylandotest'"kit:;No.  030-010  ir^).-.  1 ) C a s i l a n , G l a x o - A l l e n b u r y s , Toronto, O n t a r i o . 5 0 , 0 0 0 IU v i t a m i n A/capsule ( A f a x i n ) , Winthrop Lab., D i v , o f S t e r l i n g Drugs L t d . , Aurora, O n t a r i o .  2)  23. c. Plasma V i t a m i n A V i t a m i n A was  Determination  measured by the C a r r P r i c e  with s l i g h t modifications.  ( 1 3 6 ) method  Instead o f 2 ml plasma and  e t h y l a l c o h o l , 1 ml of each was  2 ml 9 6 %  used f o r the a n a l y s i s .  e v a p o r a t i o n under n i t r o g e n 0 . 2 ml c h l o r o f o r m was  After  added i n s t e a d  of 0 . 1 ml to each c u v e t t e and 2 ml of chromogen reagent used i n p l a c e of 1 ml.  was  O p t i c a l d e n s i t y r e a d i n g s were taken i n  a Coleman J u n i o r Spectrophotometer, Model 6C a t a wavelength of 620  mu.  d. Plasma V i t a m i n C Plasma was  Determination  analysed f o r a s c o r b i c a c i d u s i n g the  d i n i t r o p h e n y l h y d r a z i n e method adapted from Roe One  ml of plasma was  and Kuether  added to 9 ml of 5% t r i c h l o r o a c e t i c  i n s t e a d o f 2 ml plasma and 8 ml t r i c h l o r o a c e t i c a c i d . samples drawn were f r o z e n immediately a n a l y s i s was  (137).  acid,  Blood  after centrifugation  and  c a r r i e d out w i t h i n 24 hours so as t o a v o i d d e s t r u c -  t i o n of v i t a m i n G.  O p t i c a l d e n s i t y r e a d i n g s f o r plasma g l u c o s e ,  urea n i t r o g e n and a s c o r b i c a c i d were taken i n a Coleman H i t a c h i Spectrophotometer, Model 1 0 1 a t wavelengths of 4 5 0 mu,  6 3 0 mju,  and 5 1 5 n»H» r e s p e c t i v e l y .  3.  S t a t i s t i c a l Analysis The pafedst t e s t was  performed i n order t o evaluate  the r e s u l t s obtained when the d i f f e r e n t sugars were consumed 1 ) V i t a m i n A Standard was r u n u s i n g USP V i t a m i n A Reference S o l u t i o n d i s t r i b u t e d by The U n i t e d S t a t e s Pharmacopeial Convention.  24. by the same group of s u b j e c t s .  The g e n e r a l i z e d t t e s t was  to assess the responses o f the c o n t r o l s and the s u b j e c t s a f t e r consuming the same sugar.  used  intolerant  Statistical  signifi-  assumed a t or below the 5% l e v e l .  cance was  B. Ariimal.Studigs 1. E x p e r i m e n t a l  Procedures  a. The E f f e c t of L a c t o s e on the E x c r e t i o n o f F a t , N i t r o g e n and C a l c i u m To i n v e s t i g a t e the e f f e c t o f 10%,  20%,  and 30%  lactose  d i e t s on the a b s o r p t i o n of p r o t e i n , f a t and c a l c i u m , t h r e e balance s t u d i e s were c a r r i e d out on postweaning weight = 164 g) f o r t e n day p e r i o d s . balance study was  similari  rats  The procedure  (initial f o r each  twelve male Sprague-Dawley r a t s  housed s i n g l y i n metabolic cages.  S i x served as c o n t r o l s  1  were  and  r e c e i v e d the d i e t c o n t a i n i n g an amount o f sucrose e q u i v a l e n t to the l e v e l of l a c t o s e i n the d i e t f e d t o the s i x experimental animals.  The c o m p o s i t i o n o f the e x p e r i m e n t a l d i e t  balance study i n shown i n T a b l e I . ad l i b .  Food and water were f e d  Weight g a i n and food consumption were r e c o r d e d . D a i l y  u r i n e and  f e c e s c o l l e c t i o n s t a r t e d a f t e r the r a t s had been on  the d i e t s f o r 48  hours.  For each animal, u r i n e was Erlenmeyer  f l a s k c o n t a i n i n g 0.5  c o l l e c t e d i n a 125  ml 6N HC1  and  days, the pooled volume of u r i n e c o l l e c t e d was  ml  transferred  d a i l y to a l a r g e r b o t t l e f o r storage i n a f r e e z e r .  1)  i n each  After  10  measured and  Obtained from B i o Breeding L a b o r a t o r i e s , Ottawa, Canada.  25.  Table I .  Composition 10% Lactose  of D i e t s . 20% Lactose  30% Lactose  CORNSTARCH, %  53  43  33  VITAMIN FREE CASEIN, %  20  20  20  5  5  5  2  2  2  10  10  10  SALT MIXTURE,  %  X  VITAMIN MIXTURE,  %  2  CORN OIL, %  1) Rogers-Harper S a l t Mix, purchased;from C h a g r i n F a l l s , Ohio.  General Biochemicals,  The s a l t mixture contained* CaCO^,  29.29%?CaHP0^.2H 0, 0.43%} KHgPO^, 34.31%!  NaCl,  25.06%i  MgS0 7H 0, 9.98%} Fe(C H C>).6H 0, 0.623%! CuSO^,  0.156%;  2  ir  2  6  5  2  MnSO^.HgO, 0.121%} Z n C l , 0.020%j 2  (NH^) M0 0 ^.4H 0, 6  7  2  0.0025%!  2  KI, 0.0005%i  Na Se0 .5H 0, 0.0015%. 2  3  2  2) V i t a m i n D i e t F o r t i f i c a t i o n Mix., purchased B i o c h e m i c a l s Corp., C l e v e l a n d , Ohio.  from  Nutritional  The v i t a m i n mixture  c o n t a i n e d i n g/kg« v i t a m i n A c o n c e n t r a t e , 4.5 (200,000 units/g)j  v i t a m i n D c o n c e n t r a t e , 0.25 (400,000 u n i t s / g ) ;  a l p h a t o c o p h e r o l , 5.0} choline chloride, acid,  5.0}  75.0$  niacin, 4.5;  h y d r o c h l o r i d e , 1,0} pantothenate, 90}  3.0}  vitamin B , 1 2  a s c o r b i c a c i d , 45.0} menadione, 2.25s  inositol,  5.0}  p-aminobenzoic  r i b o f l a v i n , 1.0} p y r i d o x i n e  thiamine h y d r o c h l o r i d e , 1.0; c a l c i u m and i n mg/kg» b i o t i n , 20;  1.35.  folic  acid,  2(5. made up t o volume.  To o b t a i n a u n i f o r m sample, the b o t t l e  c o n t a i n i n g the u r i n e was w e l l shaken p r i o r t o a i a l y s i s . A l i q u o t s were taken d i r e c t l y f o r n i t r o g e n d e t e r m i n a t i o n .  For calcium  d e t e r m i n a t i o n u r i n e samples were f i l t e r e d through f i l t e r  paper  Whatman No. 41. Feces were c o l l e c t e d d a i l y and s t o r e d i n a f r e e z e r . A f t e r 1 0 days, the pooled f e c e s f o r each r a t were weighed and then d r i e d t o a constant weight a t 60°C i n a vacuum oven, so that moisture content c o u l d be determined.  The d r i e d f e c e s  were then ground t o a powder and a l i q u o t s were taken f o r n i t r o g e n and f a t d e t e r m i n a t i o n .  directly  I n order t o determine  "  c a l c i u m content, the d r i e d feces were ashed o v e r n i g h t i n a m u f f l e furnace a t 6 0 0 ° C .  The ash was d i s s o l v e d i n concen-  t r a t e d HC1, d i l u t e d t o make a known volume, then f i l t e r e d (as u r i n e samples) and a l i q u o t s were used f o r c a l c i u m d e t e r m i n a t i o n by atomic a b s o r p t i o n  spectrophotometry.  b. The E f f e c t o f Lactose on the A b s o r p t i o n o f Vitamin A Postweaning r a t s were used t o study t h e e f f e c t o f l a c t o s e on t h e a b s o r p t i o n o f v i t a m i n A.  I n t h i s study, 72 male  Sprague-Dawley r a t s (average weight = 2 6 3 g) were randomly d i v i d e d i n t o two groups. Each group was then s u b d i v i d e d i n t o nine l o t s o f f o u r animals  each.  experimental group r e c e i v e d  500  A f t e r an o v e r n i g h t f a s t , the mg l a c t o s e and  2500  IU v i t a m i n A  1) Trans R e t i n o l P a l m i t a t e Type V I I water d i s p e r s a b l e , Sigma Chemical Co., S t . L o u i s , Mo.  27. i n 2 ml water by stomach tube w h i l e t h e c o n t r o l group was g i v e n sucrose i n s t e a d o f l a c t o s e .  Four r a t s from each group were  s a c r i f i c e d and b l o o d was drawn by h e a r t puncture a t t h e f o l l o w i n g time i n t e r v a l s : p r i o r t o r e c e i v i n g the t e s t and a t 1, 2, 2 i , 3, 3 i . 4, of the t e s t  solution  and 5 hours a f t e r a d m i n i s t r a t i o n  solution.  2. Methods a. N i t r o g e n D e t e r m i n a t i o n U r i n a r y and f e c a l n i t r o g e n were determined  by t h e  K j e l d a h l method (138).  b. C a l c i u m Determination U r i n a r y (139) by atomic a b s o r p t i o n  and f e c a l c a l c i u m (140) were  spectrophotometry.  determined  1  c. D e t e r m i n a t i o n o f E a t Content F a t content o f f e c e s was measured u s i n g the G o l d f i s c h f a t e x t r a c t i o n apparatus  (l4l),  d. Plasma V i t a m i n A D e t e r m i n a t i o n As i n Human S t u d i e s ( I I I . A . 2 ) .  3.  S t a t i s t i c a l Analysis The g e n e r a l i z e d t t e s t was used t o assess the  s i g n i f i c a n c e o f mean values obtained f o r each  experimental  1) Unicam Atomic A b s o r p t i o n Spectrophotometer,  Model SP90;  28.  group as compared to t h e i r controls for each parameter studied. Analysis of variance was also performed to t e s t the significance of the differences between the type as well as the l e v e l of carbohydrate i n each balance study and the possible i n t e r a c t i o n of both. 5% l e v e l .  S t a t i s t i c a l significance was assumed at or below the  29.  IV. RESULTS A.  Hum§n_Studies 1. The E f f e c t o f Lactose on the A b s o r p t i o n o f P r o t e i n The  mean maximum r i s e i n plasma urea above the  f a s t i n g plasma u r e a l e v e l a f t e r i n g e s t i o n the  lactose  tolerant  of 55 g g e l a t i n by  and i n t o l e r a n t s u b j e c t s i s shown i n T a b l e  I I . (The i n d i v i d u a l v a l u e s f o r each s u b j e c t a r e i n Table I, Appendix.)  There a r e no s t a t i s t i c a l l y s i g n i f i c a n t  differences  i n the maximum r i s e i n plasma urea i n e i t h e r the t o l e r a n t or i n t o l e r a n t group whether l a c t o s e  or sucrose was consumed.  The  plasma u r e a v a l u e s obtained when the same sugar was consumed by e i t h e r group o f s u b j e c t s a l s o d i d not d i f f e r s i g n i f i c a n t l y . addition,  the mean plasma u r e a l e v e l s a t each time i n t e r v a l  were s i m i l a r f o r t h e i n t o l e r a n t s u b j e c t s and t h e c o n t r o l s 1, Appendix),  (Fig.  Consequently, peak plasma urea l e v e l s occurred  at the same i n t e r v a l (240') f o r both groups. bloating,  In  gas, cramps or d i a r r h e a  Symptoms o f  were not evident i n any o f the  subjects.  2. The E f f e c t o f Lactose on the A b s o r p t i o n o f A s c o r b i c Acid The  r e s u l t s f o r the mean maximum r i s e i n plasma  ascorbic  a c i d l e v e l s i n those s u b j e c t s who r e c e i v e d  ascorbic  a c i d a r e shown i n T a b l e I I I .  are  shown i n Table I I , Appendix.)  (The i n d i v i d u a l values  There were no s i g n i f i c a n t  differences  i n the mean r i s e i n plasma a s c o r b i c  the  i n t o l e r a n t and t o l e r a n t  lactose  500 mg o f  a c i d between  s u b j e c t s whether v i t a m i n C  30.  Table I I .  Mean Maximum R i s e + S. D. i n Plasma Urea i n Lactose T o l e r a n t and I n t o l e r a n t S u b j e c t s G i v e n 5 5 g G e l a t i n and 2 5 , 0 0 0 IU V i t a m i n A w i t h E i t h e r 5 0 . g Lactose or 5 0 g Sucrose. PLASMA UREA (mg u r e a / 1 0 0 ml) Lactose  T o l e r a n t (?) Intolerant ( 5 ) P  Sucrose  ±  5.57  10.3  ±  2.78  >  0.05  9.8 ±  3.16  10.5  +  5.03  >  0.05  >  0.05  11.7  > 0.05  Table I I I .  P  Mean Maximum R i s e ± S. D. i n Plasma A s c o r b i c A c i d i n Lactose T o l e r a n t and I n t o l e r a n t S u b j e c t s Given 5 0 0 mg V i t a m i n C and 2 5 , 0 0 0 IU V i t a m i n A w i t h E i t h e r 5 0 g Lactose or 5 0 g Sucrose.  PLASMA ASCORBIC ACID (mg v i t a m i n C / 1 0 0 ml) Lactose  Sucrose  P  Tolerant ( 6 )  0.97  ±  0.31  1.02  +  0.28  >0.05  Intolerant ( 3 )  0.93  +  0.21  0.90  +  0.40  >0.05  P  >  0.05  >  0.05  was administered  with sucrose  or l a c t o s e .  I n the t o l e r a n t  s u b j e c t s , t h e peak i n a b s o r p t i o n o f v i t a m i n C f o r 5 out o f 6 s u b j e c t s occurred a t the 180 minute i n t e r v a l when t h e v i t a m i n was consumed with l a c t o s e and a t the 120 minute i n t e r v a l when consumed w i t h sucrose not c o n s i d e r e d maximum r i s e  ( F i g . 2, Appendix).  statistically significant.  This difference i s The v a l u e s  i n plasma v i t a m i n C w i t h sucrose  s i m i l a r i n the i n t o l e r a n t subjects.  f o r the  or l a c t o s e a r e  In a d d i t i o n , the i n g e s t i o n  of l a c t o s e or sucrose seemed t o have no e f f e c t on the mean maximum r i s e i n plasma a s c o r b i c a c i d when t h e s u b j e c t s as t h e i r own c o n t r o l s .  Symptoms o f gas and b l o a t i n g , cramps  and d i a r r h e a were r e p o r t e d The  served  i n some o f the i n t o l e r a n t s u b j e c t s .  r e s u l t s i n T a b l e IV show the maximum r i s e i n  plasma a s c o r b i c a c i d l e v e l s i n k i n t o l e r a n t s u b j e c t s who r e c e i v e d 1 g v i t a m i n C w i t h a t e s t meal. v a l u e s a r e shown i n T a b l e I I I , Appendix.)  (The i n d i v i d u a l The mean r i s e i n  plasma a s c o r b i c a c i d a f t e r the l a c t o s e meal, 1 . 0 5 mg v i t a m i n C/100  ml plasma, does not d i f f e r s i g n i f i c a n t l y  from t h a t  obtained when these s u b j e c t s consumed t h e sucrose meal, 1 . 0 3 mg v i t a m i n C/100 ml plasma. unaffected  A b s o r p t i o n r a t e s a l s o remain  ( F i g . 3 i Appendix).  Because o f the s m a l l sample  s i z e , one must always be c a r e f u l i n drawing c o n c l u s i o n s such d a t a .  from  In a d d i t i o n , the symptomatic response o f our  s u b j e c t s i n t h i s experiment was reduced probably  due t o  consumption o f the l a c t o s e i n the form o f a meal r a t h e r than a drink.  32.  Table IV.  Mean Maximum R i s e + S. D. i n Plasma A s c o r b i c A c i d i n Lactose I n t o l e r a n t S u b j e c t s G i v e n 2 0 0 , 0 0 0 IU V i t a m i n A and 1 g V i t a m i n C w i t h a T e s t Meal C o n t a i n i n g 15 g C a s i l a n , 2 5 ml O l i v e O i l and E i t h e r 45 g Lactose or 45 g Sucrose.  PLASMA ASCORBIC ACID (mg v i t a m i n C/100 ml) Lactose  Sucrose  I n t o l e r a n t (4) 1 . 0 5 + 0.048  T a b l e V.  1.03  t  >  0.232  0.05  Mean Maximum R i s e ± S. D. i n Plasma V i t a m i n A i n Lactose I n t o l e r a n t S u b j e c t s Given 200,000 IU V i t a m i n A and 1 g V i t a m i n C w i t h a T e s t Meal C o n t a i n i n g 1$ g C a s i l a n , 25 ml O l i v e O i l , and E i t h e r 45 g Lactose or 453g Sucrose. PLASMA VITAMIN A (mg v i t a m i n A / 1 0 0 ml) Lactose  I n t o l e r a n t (4)  0.012  ±  0.0085  Sucrose 0.031  +  0.0239  P >o.05  33.  3 . The E f f e c t o f Lactose on the A b s o r p t i o n o f V i t a m i n A The mean r i s e i n plasma v i t a m i n A l e v e l s when f o u r l a c t o s e i n t o l e r a n t s u b j e c t s consumed a meal w i t h v i t a m i n A a r e shown i n Table V, shown i n T a b l e IV, Appendix.)  200,000  IU  (Values f o r each s u b j e c t a r e  The mean maximum r i s e i n plasma  v i t a m i n A was s l i g h t l y lower a f t e r the l a c t o s e meal as compared t o the value obtained a f t e r the sucrose meal.  The d i f f e r e n c e  however, between these two v a l u e s i s not s t a t i s t i c a l l y i c a n t a t the 5 % l e v e l .  signif-  I n a d d i t i o n , the peak a b s o r p t i o n f o r  v i t a m i n A was reached a f t e r the same time i n t e r v a l whether or not l a c t o s e o r sucrose was consumed w i t h the v i t a m i n .  B.  Animal_Studies 1. The E f f e c t o f L a c t o s e on the E x c r e t i o n o f F a t , N i t r o g e n and C a l c i u m a. : Body Weight G.ain and Food Consumption The mean cumulative weight  g a i n and food consumption  of each group o f r a t s on the v a r i o u s d i e t s a r e shown i n T a b l e s VI and V I I .  Weight g a i n was s i g n i f i c a n t l y lower  (p<0.05)  in  the e x p e r i m e n t a l animals f e d the 2 0 % and 3 0 % l a c t o s e d i e t s as compared t o t h e i r c o r r e s p o n d i n g c o n t r o l s .  Food consumption  was a l s o lower f o r these same animals, although the d i f f e r e n c e between the c o n t r o l s and e x p e r i m e n t a l animals i s s t a t i s t i c a l l y significant  (p < 0 . 0 5 ) only on the 3 0 % d i s a c c h a r i d e d i e t s .  would suggest t h a t feed e f f i c i e n c y i s reduced a t the h i g h e r levels of dietary  lactose.  This  34. Table VI.  DIET  Mean Weight Gain + S. D. of Experimental and Control Animals Over a Ten Day Period. (N = 6 ) WEIGHT GAIN ( g / 1 0 days)  1 0 % Lactose  87.3  + 4.63  1 0 % Sucrose  86.2  + 8.02  2 0 % Lactose  73.8  +  2 0 % Sucrose  83.8  + 8.90  3 0 % Lactose  53.1  + 18.83  3 0 % Sucrose  74.4  +  Table VII.  > 0 . 0 5  5.93 < 0.05  < 0 . 0 5 6.71  Average Food Consumption + S. D. of Experimental and Control Animals Over a Ten Day Period. (  DIET  P  N =  6  )  FOOD CONSUMPTION (g/10 days)  10% Lactose  174.0 ± 6.75  20% Sucrose  178.7 ± 16.77  20% Lactose  177.9 + 5.75  20% Sucrose  191.9 + 15.95  3 0 % Lactose  142.0  3 0 % Sucrose  173.7 + 14.42  P  >0.05  > 0.05  + 26.57  < 0.05  35.  Loose s t o o l s were apparent i n the 3 ° % l a c t o s e group, i n d i c a t i n g t h a t d i a r r h e a was lactose intake.  induced  by the high l e v e l  These r a t s , too, as a group, appeared to  s l i g h t l y more i r r i t a b l e than those i n any However, there were u s u a l l y one d i e t a r y groups whose behavior o f food  of  or two  was  f o r the l a r g e standard  o f the other groups.  animals i n the  slightly erratic.  i n t o e x c r e t a o f t e n occurred  other Spillage  i n such cases and  d e v i a t i o n s i n the r e s u l t s .  observed t h a t the u r i n e volume was  accounts  I t was  c o n s i s t e n t l y greater  l e v e l s increased.  also  as  d i e t a r y l a c t o s e l e v e l s i n c r e a s e d , w h i l e the r e v e r s e was as sucrose  be  true  At the 3 0 % l e v e l of d i s a c c h a r i d e  i n t a k e , the d i f f e r e n c e i n u r i n e volume between the c o n t r o l s (mean =  135.0+  (mean =  255.8  14.14  m l s / 1 0 days) and  + 79.08 m l s / 1 0 days) i s s t a t i s t i c a l l y  a t the 5% l e v e l .  The  values  significant  on F e c a l Fat  Excretion  f o r f e c a l f a t e x c r e t i o n as per cent  f a t i n t a k e i n the c o n t r o l and i n Table V I I I .  group  reason f o r t h i s f i n d i n g i s not c l e a r .  b. T h e . E f f e c t of _Lacto.se The  the experimental  experimental  Significant differences  of  animals are shown in fecal  (p<0.05)  e x c r e t i o n of f a t are a s s o c i a t e d w i t h both the type of c a r b o hydrate and  l e v e l of carbohydrate i n the d i e t s .  words, f a t e x c r e t i o n was  In  other  g r e a t e r for>the experimental  r e l a t i v e t o t h e i r c o n t r o l s i a l s o f a t e x c r e t i o n was  animals  least for  both groups on the 1 0 % d i s a c c h a r i d e d i e t s , as compared t o the animals on the 2 0 % and t h e r e i s no  3 0 % disaccharide d i e t s .  In a d d i t i o n  i n t e r a c t i o n between the type o f d i s a c c h a r i d e s  and  T a b l e VIII.  E f f e c t of D i f f e r e n t Levels of Dietary Lactose on F e c a l E x c r e t i o n o f Fat.; (N = 6)  DIET  Mean F e c a l F a t E x c r e t i o n as % F a t Intake + S.D.  10% L a c t o s e  3.75 ± 0.94  10% Sucrose  2.30  20% L a c t o s e  6.54 + 2 . 3 6  20% Sucrose  3.42 ±  3 0 % Lactose  4.43 + 0.72  3 0 % Sucrose  3.51 ± 0.55  Source o f V a r i a t i o n 1. Type o f carbohydrate  *  + 0.14  1.03  F*  P**  21.5393  0.00006  2. L e v e l o f carbohydrate  8.2274  0.00142  3. I n t e r a c t i o n o f 2 and 3  2.824?  0.07526  F = r a t i o o f mean squares o f treatment t o mean squares of e r r o r  ** P = p r o b a b i l i t y t h a t e f f e c t o f treatments i s due t o chance  37. t h e i r l e v e l i n t h e d i e t j so t h a t the presence o f l a c t o s e would be s u f f i c i e n t t o a f f e c t  fecal excretion of fat.  c. The E f f e c t o f Lactose Nitrogen Excretion The  values  on F e c a l and U r i n a r y  f o r f e c a l n i t r o g e n e x c r e t i o n as p e r cent  of n i t r o g e n i n t a k e are presented  i n Table  n i t r o g e n i n feces i s £ s i g n i f i c a n t l y  IX.  Excretion of a f f e c t e d by the  (p<0.05)  type and l e v e l o f d i e t a r y carbohydrate allhough there interaction  alone  between the two.  i s no  Those animals f e d the l a c t o s e  d i e t s showed a g r e a t e r e x c r e t i o n o f f e c a l n i t r o g e n r e l a t i v e t o the s u c r o s e - f e d  r a t s j as d i e t a r y l a c t o s e l e v e l s  increased,  fecal  e x c r e t i o n o f n i t r o g e n was g r e a t e r . As  seen i n Table X; u r i n a r y n i t r o g e n e x c r e t i o n as  per cent o f n i t r o g e n i n t a k e i s s i g n i f i c a n t l y  (p<0.05)  only by the l e v e l o f carbohydrate i n the d i e t . e i t h e r l a c t o s e or sucrose u r i n e , and t h i s e f f e c t disaccharides  of calcium  Therefore,  may i n c r e a s e n i t r o g e n e x c r e t i o n i n  i s more apparent as l e v e l s  o f these  i n the d i e t are i n c r e a s e d .  d. The E f f e c t o f Lactose Calcium E x c r e t i o n The  on F e c a l and U r i n a r y  r e s u l t s f o r f e c a l c a l c i u m e x c r e t i o n as p e r cent  i n t a k e a r e shown i n Table X I .  Fecal  calcium  e x c r e t i o n f o r each l a c t o s e group i s s i g n i f i c a n t l y lower not only from i t s corresponding each sucrose  affected  sucrose  (p<0.05)  group but a l s o from  group i n the two other balance s t u d i e s .  38.  Table IX.  E f f e c t o f D i f f e r e n t Levels o f Dietary Lactose on F e c a l E x c r e t i o n o f N i t r o g e n . (N =  DIET  Mean F e c a l N E x c r e t i o n as % N Intake + S. D.  10% Lactose  5.02  +  0.91  1 0 % Sucrose  3.71  +  0.55 ;  2 0 % Lactose  5.23  ±  0.32  20%  3.68 +  0.19  3 0 % Lactose  6.11  +  0.92  30%  4.22  +  0.48  Sucrose  Sucrose  Source o f V a r i a t i o n  *  6)  F*  1.  Type o f carbohydrate  2.  L e v e l o f carbohydrate  3.  Interaction of  2  and  3  ? 1,  P**  57.4257  0.00000  5.9170  0.00683  0.6343  0.53795  F = r a t i o o f mean squares o f treatment t o mean squares o f e r r o r  ** P = p r o b a b i l i t y t h a t e f f e c t o f treatments chance  i s due t o  39. T a b l e X.  E f fecit o f Different L e v e l s o f D i e t a r y Lactose on U r i n a r y E x c r e t i o n o f N i t r o g e n . (N = 6)  DIET  Mean U r i n a r y N E x c r e t i o n as % N Intake + S.D.  10% L a c t o s e  36.97 + 2 . 5 1  10%  Sucrose  38.95 + 3 . 6 5  20% L a c t o s e  42.6? ± 5.55  20%  Sucrose  43.96 + 4.54  3 0 % Lactose  36.88 + 6.97  30%  42.06 + 4.18  Sucrose  Source o f V a r i a t i o n  *  F* }••'•  1. Type o f carbohydrate  3.1281  0.08725  2. L e v e l o f carbohydrate  4.0019  0.02884  3. I n t e r a c t i o n o f 2 and 3  0.5651  0.57496  F = r a t i o o f mean squares o f treatment t o mean squares o f e r r o r  ** P = p r o b a b i l i t y t h a t e f f e c t o f treatments t o chance  i s due  \  Table XI. E f f e c t of D i f f e r e n t Levels of Dietary Lactose on F e c a l E x c r e t i o n o f Calcium. (N = DIET  Mean F e c a l C a l c i u m E x c r e t i o n as % i n t a k e + S.D.  1 0 % Lactose  45.12  +  13.15  1 0 % Sucrose  51.42  +  4.10  2 0 % Lactose  38.14  +  7.00  2 0 % Lactose  44.05  i  3.50  3 0 % Lactose  28.20  +  6.10  3 0 % Sucrose  56.07  +  7.03  Source o f V a r i a t i o n  *  6)  F*  1.  Type o f carbohydrate  2.  L e v e l o f carbohydrate  3.  Interaction of  2  and  3  P**  28.5810  0.00001  3.2055  0.05481  8.4349  0.00124  F = r a t i o o f mean squares o f treatment t o mean squares o f e r r o r  ** P = p r o b a b i l i t y t h a t e f f e c t o f treatments i s due to chance  41. A c c o r d i n g t o the r e s u l t s i n T a b l e X I I , u r i n a r y c a l c i u m e x c r e t i o n i s s i g n i f i c a n t l y a f f e c t e d by the type and l e v e l o f carbohydrate of both.  i n t h e d i e t , as w e l l as the i n t e r a c t i o n  A t the 1 0 % l e v e l o f d i e t a r y l a c t o s e , c a l c i u m e x c r e -  t i o n i n u r i n e i s lower than a t the 2 0 % and 3 0 % d i e t a r y  lactose  On the 2 0 % and 3 0 % l a c t o s e d i e t s , u r i n a r y c a l c i u m  levels.  e x c r e t i o n i s n o t only h i g h e r r e l a t i v e t o t h e i r  corresponding  c o n t r o l s , but a l s o as compared t o the c o n t r o l s i n the two other balance s t u d i e s .  T h i s might be due t o the f i n d i n g t h a t  f e c a l c a l c i u m e x c r e t i o n i s lower present i n t h e d i e t .  (Table XI) when l a c t o s e i s  T h i s i n d i c a t e s an i n c r e a s e i n c a l c i u m  uptake, which might account  f o r higher l e v e l s of calcium  in urine.  2 . The E f f e c t o f Lactose on the A b s o r p t i o n o f V i t a m i n A The mean plasma v i t a m i n A l e v e l s reached intragastric administration of  2500  after  IU o f r e t i n o l p a l m i t a t e  w i t h e i t h e r 5 0 0 mg l a c t o s e or sucrose t o postweaning r a t s a r e shown i n T a b l e X I I I .  Peak a b s o r p t i o n occurred f o r both groups  a t the two hour time i n t e r v a l .  Although t h i s v a l u e i s h i g h e r  i n the l a c t o s e group, the d i f f e r e n c e i s n o t s t a t i s t i c a l l y significant  (p>  0.05).  The maximum mean plasma v i t a m i n A r i s e  ( d i f f e r e n c e between the mean f a s t i n g plasma v i t a m i n A value and the maximum mean plasma v i t a m i n A r i s e ) i n the experimental group  (0.1936  mg v i t a m i n A / t o t a l blood volume) i s s l i g h t l y  h i g h e r as w e l l r e l a t i v e t o the c o n t r o l s t o t a l blood volume).  (0.1476  mg v i t a m i n A/  The v a l u e s between the c o r r e s p o n d i n g  Table XII.  E f f e c t of D i f f e r e n t Levels of Dietary Lactose on U r i n a r y E x c r e t i o n o f Calcium. (N = 6)  DIET  Mean U r i n a r y C a l c i u m E x c r e t i o n as % Ca Intake + S. D.  10% L a c t o s e  1.28 + 0.27  10% Sucrose  1.38 ± 0.71  20 % L a c t o s e  1.64 ± 0.59  20% Sucrose  0.62 + 0.23  30% Lactose  2.87 + 0.48  30% Sucrose  1.34 + 0.84  Source o f V a r i a t i o n  *  F*  P**  1. Type o f carbohydrate  20.5826  0.00009  2. L e v e l o f carbohydrate  17.5576  0.00001  3. I n t e r a c t i o n o f 2 and 3  10.0167  0.00047  F = r a t i o o f mean squares o f treatment t o mean squares o f e r r o r  ** P = p r o b a b i l i t y t h a t e f f e c t o f treatments i s due t o chance  43.  Table X I I I .  Mean Plasma V i t a m i n A L e v e l s i n Postweaning Rats A f t e r I n t r a g a s t r i c A d m i n i s t r a t i o n o f 2 5 0 0 IU o f V i t a m i n A w i t h E i t h e r 5 0 0 mg Lactose or 5 0 0 mg Sucrose ( 4 animals p e r subgroup).  Time Interval (hrs) Fasting  mg v i t a m i n A / t o t a l blood volume* Lactose ± S.D. Sucrose ±S.D. 0.0702 +  0.0669  +  0.070  > .05  1.0  0.1725 + 0.073  0.2082 +  0.090  > .05  2.0  0.2638 + 0.124  0.2145 + 0.180  > .05  2.5  0.2435 + 0.064  0.1686 + 0.040  >  .05  3.0  0.1249 + 0.027  0.1822 +  0.097  >  .05  3.5  0.0932  0.020  0.1227 +  0.057  > .05  4.0  0.1215 + 0.018  0.1273 ± 0.015  > .05  4.5  0.1506  +  0.058  > .05  5.0  0.1399  + 0.016  Maximum Mean R i s e i n Plasma V i t a m i n A  *  0.023  P  +  0.046  0.1936  0.1153  ±  0.0916  + 0.016  < .05  0.1476  T o t a l b l o o d volume = (mg v i t a m i n A/ ml) x weight/rat)  (4.3%**  x body  ** T h i s f i g u r e r e p r e s e n t s the r a t i o o f blood volume t o body weight ( 4 . 3 ml/100 g) i n the r a t . (Rowett, H.G.Q. The r a t as a smalL mammal. London. John Murray ( P u b l i s h e r s ) L t d . , I960, p.40.)  44. points on the vitamin A absorption curve ( F i g . 5 . Appendix) differ significantly  (p<0.05)  f o r controls and the experimen-  t a l animals only at the 5 hour i n t e r v a l .  In addition, the r a t s  that received the sucrose s o l u t i o n appeared to be more e a s i l y excitable and showed signs of diarrhea which sets c e r t a i n l i m i t a t i o n s i n interpretation of these findings.  *5. V. DISCUSSION A.  Human_Studies Results  not  obtained  i n t h i s study w i t h human s u b j e c t s  i n d i c a t e t h a t l a c t o s e has  v i t a m i n A,  any  e f f e c t on the a b s o r p t i o n  a s c o r b i c a c i d or p r o t e i n i n l a c t o s e t o l e r a n t  intolerant subject.  The  findings with regard  agree w i t h those of Paige and Graham (32), Chenoweth (33). higher  who  of  and  t o p r o t e i n do  or Calloway  were r e l a t e d tqittiejlevel of d i e t a r y l a c t o s e .  not  and  found t h a t l a c t o s e i n t o l e r a n t s u b j e c t s  f e c a l l o s s e s of moisture, dry s o l i d s and  do  had  energy which  Because o f d i f f e r -  ences i n experimental procedure, i t i s d i f f i c u l t t o compare t h e i r r e s u l t s w i t h those of the present Paige and Graham (32), Chenoweth (33).  study.  as w e l l as Calloway  and  conducted balance s t u d i e s o f n u t r i e n t s over an  extended p e r i o d o f time.  In the p r e s e n t  study, changes i n  plasma urea l e v e l s only over a f o u r hour p e r i o d were used as a measure o f p r o t e i n a b s o r p t i o n .  Therefore  the  fact  l a c t o s e had no e f f e c t on plasma urea l e v e l s does not i l y mean t h a t t h e r e were no d i f f e r e n c e s i n the absorption  o f the p r o t e i n .  The  use  that necessar-  absolute  of balance s t u d i e s  s u i t a b l e f o r a s s e s s i n g the n u t r i t i o n a l s i g n i f i c a n c e of e f f e c t of l a c t o s e on p r o t e i n a b s o r p t i o n . the e f f e c t of l a c t o s e on the a b s o r p t i o n  the  Similar studies of v i t a m i n A  a s c o r b i c a c i d have not been r e p o r t e d . T h e r e f o r e , b a s i s f o r comparison.  i s more  there  of  and i s no  46. As p o i n t e d out B.3.)  the  f a t and  i t s e l f , may intolerant  i n the  protein  components of a meal, or the  a l l e v i a t e the  symptomatic response of a  i n d i v i d u a l , probably due  emptying time and  i n the  f a t and  The  or no  lactose  (122,123-127).  intolerant  s u b j e c t s who  In  the  consumed  abdominal d i s c o m f o r t d u r i n g the  presence of the p r o t e i n  protein  c o n t a i n e d i n the  g a s t r i c emptying and  i n the  o f those i n t o l e r a n t  testing  t e s t d r i n k , or  t e s t meal, may  i n d i v i d u a l s who  s o l u t i o n alone.  symp-  symptomatic response  r e c e i v e d the  In a d d i t i o n ,  the  have delayed  thus reduced the abdominal d i s t r e s s  toms i n these s u b j e c t s , as compared to the  lactose  milk  t e s t d r i n k c o n t a i n i n g g e l a t i n or i n a t e s t meal,  reported l i t t l e period.  II.  to a d e l a y i n g a s t r i c  a dilution effect  p r e s e n t study, most of the lactose  l i t e r a t u r e review ( S e c t i o n  aqueous  as K o c i a n et a l .  (121)  suggest, t h i s d e l a y i n g a s t r i c emptying i s important f o r n u t r i ent  a b s o r p t i o n to occur i n i n d i v i d u a l s w i t h low  T h i s may  a l s o be the r e a s o n why  v i t a m i n s A and not  C,  and  protein  the  rate  i n the  sumed i n the  solution  (without g e l a t i n and  v i t a m i n C l e v e l s d i d not drink i n lactose f i n d i n g i s not c o n t a i n any  subjects.  really clear.  f a t or p r o t e i n  The  of  subjects  or i n the  did con-  t e s t meal.  g i v e n w i t h an an aqueous v i t a m i n A),  plasma  d i f f e r from those a f t e r the  intolerant  levels.  or sucrose was  test drink containing protein  However, when v i t a m i n C was lactose  of a b s o r p t i o n  intolerant  d i f f e r s i g n i f i c a n t l y whether l a c t o s e  lactase  The  sucrose  explanation for t h i s  t e s t s o l u t i o n here d i d  components t h a t may  not  have caused a  47.  delay i n gastric emptying and thus a l l e v i a t e d the symptomatic response and possibly improved absorption of acorbic a c i d . Perhaps 500 mg was too small an amount to show measurable difference i n blood levels of vitamin C which might have been manifest with larger amounts of ascorbic acid. From these studies with human subjects, i t would appear that protein, ascorbic acid and vitamin A absorption i s not affected by lactose intolerance.  One may. conclude that under  normal dietary conditions a lactose intolerant i n d i v i d u a l would probably not experience s i g n i f i c a n t losses of nutrients,when consuming milk or lactose-containing  products.  48. B. Animal_Studies 1. The E f f e c t o f Lactose Fat and Calcium The  on the E x c r e t i o n o f N i t r o g e n ,  balance s t u d i e s i n d i c a t e t h a t postweaning r a t s  on l a c t o s e - c o n t a i n i n g d i e t s show g r e a t e r e x c r e t i o n o f n i t r o g e n , and  f a t but not calcium,  sucrose  diets.  increased,  as compared t o postweaning r a t s on  Furthermore, as d i e t a r y l a c t o s e l e v e l s  f e c e s were o f s o f t e r c o n s i s t e n c y and f e c a l l o s s e s o f  n i t r o g e n and f a t i n c r e a s e d .  Medler e t a l . (142) a l s o noted  t h a t f e e d i n g an i n f a n t m i l k formula t o weanling r a t s r e s u l t s i n diarrhea«iand a decrease i n net p r o t e i n u t i l i z a t i o n from 88% to 67% as compared t o f e e d i n g a formula t h a t was t r e a t e d lactase.  with  Our f i n d i n g s a l s o agree w i t h those o f Paige and  Graham (32) and Calloway and Chenoweth (33) who observed s i m i l a r l o s s e s w i t h r e s p e c t t o f e c a l n i t r o g e n and f a t e x c r e t i o n i n lactose intolerant individuals.  The e f f e c t o f l a c t o s e on  c a l c i u m e x c r e t i o n was not i n v e s t i g a t e d by these workers. In the balance study by Paige and Graham (32), n i t r o g e n e x c r e t i o n i n c r e a s e d from 7% i n l a c t o s e i n t o l e r a n t c h i l d r e n who r e c e i v e d sucrose-based d i e t s t o 17% when these same c h i l d r e n r e c e i v e d l a c t o s e d i e t s .  I n the present  balance  study, f e c a l n i t r o g e n e x c r e t i o n i n the c o n t r o l s was 3.71%, 3.68% and 4.22% o f n i t r o g e n intake on the 10%, 20% and 30% disaccharide d i e t s r e s p e c t i v e l y , while  i n the  experimental  groups, mean f e c a l n i t r o g e n e x c r e t i o n was 5.02%, 5.23% and 6.11% of nitrogen intake.  Although these d i f f e r e n c e s i n n i t r o g e n  losses are s t a t i s t i c a l l y s i g n i f i c a n t  (p <0.05), i t i s d o u b t f u l  49. that they a r e o f p r a c t i c a l s i g n i f i c a n c e .  I n terms o f an average  d a i l y l o s s o f n i t r o g e n , a l o s s o f 1 or 2% o f the n i t r o g e n would not be s e r i o u s .  intake  The n u t r i t i o n a l consequences o f a 10%  i n c r e a s e i n f e c a l n i t r o g e n e x c r e t i o n , as r e p o r t e d by Paige and Graham (32),  would be s i g n i f i c a n t i n an i n t o l e r a n t i n d i v i d u a l  whose d i e t a r y p r o t e i n was marginal. Graham (32)  In a d d i t i o n , Paige and 60%  f e d t h e i r s u b j e c t s a d i e t c o n t a i n i n g almost  l a c t o s e as compared t o the h i g h e s t d i e t a r y l e v e l o f l a c t o s e o f 30% i n the p r e s e n t  study.  T h i s may account f o r the more p r o -  nounced e f f e c t o f l a c t o s e on f e c a l n i t r o g e n e x c r e t i o n seen i n t h e i r study. Paige and Graham (32)  a l s o noted an i n c r e a s e i n s t o o l  f a t from 3 g t o 5 g/day when l a c t o s e i n t o l e r a n t c h i l d r e n were g i v e n l a c t o s e d i e t s a f t e r r e c e i v i n g sucrose-based d i e t s . r e s u l t s from the present  balance s t u d i e s w i t h r a t s i n d i c a t e  t h a t f a t e x c r e t i o n expressed as p e r cent o f f a t i n t a k e V I I I ) was s i g n i f i c a n t l y g r e a t e r i n the experimental i n the c o n t r o l s . represent 3.12% and  The  However, the f i g u r e s r e p o r t e d  (Table  groups than  i n Table  VIII  a maximum d i f f e r e n c e i n f e c a l f a t e x c r e t i o n o f only  ( a t the 20% l e v e l o f l a c t o s e i n t a k e ) between the c o n t r o l s the experimental  animals.  F i n a l l y , Paige and Graham (32)  r e p o r t e d an i n c r e a s e  i n d a i l y s t o o l weight from 38g/day t o l4?g/day when the l a c t o s e children i n t o l e r a n t ^ r e c e i v e d a l a c t o s e d i e t as compared t o a diet.  sucrose  I t i s l i k e l y t h a t i n t e n s e abdominal d i s t r e s s symptoms,  such as d i a r r h e a , were present  i n these c h i l d r e n due t o the  50. high l e v e l of d i e t a r y l a c t o s e . s t o o l weight i n c r e a s e d the  I n the present balance study,  by approximately 23%  i n the r a t s  l a c t o s e d i e t s r e l a t i v e to the c o n t r o l s .  l e v e l s increased, were e v i d e n t .  l o o s e r s t o o l s and  The  r a t s fed the  feces than those f e d the 10% r e c e i v i n g the 30%  20%  As  dietary  softer fecal  softer  Only the  rats  l a c t o s e d i e t seemed to s u f f e r from  With r e s p e c t  to c a l c i u m a b s o r p t i o n ,  lactose  consistency  l a c t o s e d i e t had  lactose diet.  fed  diarrhea.  the r e s u l t s from  the p r e s e n t balance study i n d i c a t e t h a t l a c t o s e reduced f e c a l losses  of c a l c i u m i n r a t s , p a r t i c u l a r l y at the 30%  lactose intake.  These f i n d i n g s are  a number of workers (143-14?) who lactose stimulates  level  of  i n agreement w i t h those  have r e p e a t e d l y  found  of  that  c a l c i u m uptake from the r a t i n t e s t i n e .  One  of the hypotheses proposed t o e x p l a i n t h i s phenomenon i s t h a t lactic  a c i d produced by b a c t e r i a l a c t i o n on the  i n t e s t i n a l lumen lowers the pH, f a v o u r a b l e to c a l c i u m uptake.  lactose  creating conditions Pansu and  more  Chapuy (143)  t h a t i n humans as w e l l , c a l c i u m a b s o r p t i o n l a c t o s e consumption i n i n d i v i d u a l s w i t h low  was  i n the  noted  improved  by  lactase l e v e l s .  They suggested t h a t l a c t o s e w i l l cause» a hyperosmolar i n t r a l u m i n a l e f f e c t , water s e c r e t i o n i n t o the lumen and i n v e r s e t r a n s f e r across the membrane. C o n d i t i o n s then, f a v o r i n g l a c t o s e accumulation i n the  intes-  t i n a l lumen would enhance c a l c i u m uptake.  Such  existed  l a r g e l e v e l s of  i n the p r e s e n t work due  dietary lactose. the  As  the  to feeding  conditions  l e v e l of d i e t a r y l a c t o s e  i n t e n s i t y of the g a s t r o i n t e s t i n a l d i s t u r b a n c e s  increased, increased.  51.  There was a l s o a concomitant improvement i n c a l c i u m a b s o r p t i o n . T h e r e f o r e , the t h e o r i e s proposed above t o e x p l a i n the e f f e c t of l a c t o s e on c a l c i u m a b s o r p t i o n seem t o be supported r e s u l t s obtained i n the p r e s e n t balance  by the  study.  However, a c c o r d i n g t o these same c r i t e r i a  i t is  d i f f i c u l t t o e x p l a i n the r e s u l t s o f Kocian e t a l . ( 1 2 1 ) t h a t l a c t o s e seemed t o improve the r a t e o f c a l c i u m uptake i n l a c t o s e tolerant subjects.  I n a d d i t i o n , these same i n v e s t i g a t o r s noted  no d i f f e r e n c e i n c a l c i u m uptake i n l a c t o s e i n t o l e r a n t s u b j e c t s who consumed m i l k and l a c t o s e f r e e m i l k . The f i n d i n g of K o c i a n e t a l . ( 1 2 1 ) t h a t l a c t o s e had no e f f e c t on c a l c i u m a b s o r p t i o n i n l a c t o s e i n t o l e r a n t s u b j e c t s may be e x p l a i n e d i n the f o l l o w i n g way.  Because the m i l k s o l u t i o n s  c o n t a i n e d f a t and p r o t e i n , g a s t r i c emptying time was probably del a y e d and i n t h i s way, i n t e s t i n a l l a c t a s e was n o t overloaded lactose.  with  Consequently, there was l i t t l e change i n g a s t r o i n t e s -  t i n a l m o t i l i t y and c a l c i u m a b s o r p t i o n was not improved.  However,  i t may a l s o be argued t h a t c a l c i u m a b s o r p t i o n was i n f a c t i n c r e a s e d a f t e r the m i l k was consumed because the probable  delay i n  g a s t r i c emptying allowed s u f f i c i e n t time f o r c a l c i u m a b s o r p t i o n to  occur.  I f one accepts the l a t t e r e x p l a n a t i o n , i t then  becomes p o s s i b l e t o account f o r the r e s u l t s obtained by Kocian et a l . ( 1 2 1 ) w i t h t o l e r a n t s u b j e c t s . . T h i s suggests  that lactose  enhances c a l c i u m a b s o r p t i o n i n t o l e r a n t and i n t o l e r a n t u a l s , however, the t h e o r i e s proposed t o e x p l a i n t h i s which a r e based on t h e accumulation  individ-  phenomenon  o f l a c t o s e , must be r e j e c t e d .  52. I f l a c t o s e enhances t o t a l c a l c i u m a b s o r p t i o n , as  the  r e s u l t s from the p r e s e n t balance s t u d i e s i n d i c a t e , and. t h i s e f f e c t i s p r o p o r t i o n a l to the l e v e l o f l a c t o s e i n the such an e f f e c t may  have important  d i e t a r y c a l c i u m i n t a k e i s low.  diet,  n u t r i t i o n a l i m p l i c a t i o n where  However, the p r a c t i c a l  signif-  icance of the e f f e c t of l a c t o s e on f a t and p r o t e i n a b s o r p t i o n is doubtful.  I t appears not only from the p r e s e n t study  but  a l s o from the work of Paige and Graham (32) t h a t the l e v e l of d i e t a r y l a c t o s e necessary  to i n t e r f e r e with n u t r i e n t absorption  would far, exceed the l i m i t s of normal d i e t a r y consumption.  2. The E f f e c t of Lactose on the A b s o r p t i o n of V i t a m i n A The r e s u l t s from the v i t a m i n A a b s o r p t i o n study i n r a t s i n d i c a t e t h a t l a c t o s e d i d not impair v i t a m i n A a b s o r p t i o n and even seemed to improve i t . However, as compared t o the l a c t o s e group, the r a t s t h a t r e c e i v e d the sucrose appeared to be more e x c i t a b l e , which may  solution  have c o n t r i b u t e d to  the o b s e r v a t i o n t h a t they were a l s o s u f f e r i n g from d i a r r h e a . These g a s t r o i n t e s t i n a l d i s t u r b a n c e s which were e v i d e n t i n the sucrose group may  have n u l l i f i e d the e f f e c t of l a c t o s e on  v i t a m i n A a b s o r p t i o n i n the l a c t o s e group.  x'Mii  53. VI.  RECOMMENDATIONS In Canada, i t i s estimated t h a t some 6.5 m i l l i o n  people, or approximately 30% o f the t o t a l Canadian are  lactose i n t o l e r a n t . 1  population,  I f a l l these i n d i v i d u a l s a r e s u s t a i n -  i n g l o s s e s o f important n u t r i e n t s due t o l a c t o s e consumption, as suggested by r e c e n t  studies.(32,33) then t h i s might become  an a r e a of p u b l i c h e a l t h concern i n Canada.  The r e s u l t s o f the  p r e s e n t work suggest t h a t under normal d i e t a r y absorption  conditions,  o f n u t r i e n t s may not be a f f e c t e d by l a c t o s e  intolerance.  However, f u t u r e r e s e a r c h  i s needed t o determine  the v a l i d i t y o f t h i s s u g g e s t i o n . A t t e n t i o n s h o u l d be focused on t h e d i e t a r y  modifi-  c a t i o n o f t h e symptomatic response o f a l a c t o s e i n t o l e r a n t i n d i v i d u a l , and what e f f e c t t h i s m o d i f i c a t i o n has on a b s o r p t i o n . I t should be e s t a b l i s h e d whether or not a l l e v i a t i o n o f g a s t r o i n t e s t i n a l symptoms by consuming l a c t o s e w i t h a meal, i s r e l a t e d t o improved n u t r i e n t a b s o r p t i o n  i n i n d i v i d u a l s w i t h low l a c t a s e  levels. A l a r g e r number o f s u b j e c t s  should be used t o study  the e f f e c t o f l a c t o s e on the a b s o r p t i o n  of various  nutrients  i n order t o o b t a i n s i g n i f i c a n t r e s u l t s . I n a d d i t i o n , c o n d u c t i n g balance s t u d i e s w i t h humans, b e s i d e s measuring blood l e v e l s o f the v a r i o u s  1)  n u t r i e n t s , would a i d i n the i n t e r p r e t a t i o n o f the  These f i g u r e s a r e based on c a l c u l a t i o n s d e r i v e d from (1)19?1 S t a t i s t i c s Canada f i g u r e s f o r the d i f f e r e n t e t h n i c p o p u l a t i o n s i n Canada and (2) the v a l u e s f o r the i n c i d e n c e o f l a c t o s e i n t o l e r a n c e f o r these e t h n i c groups t h a t have been r e p o r t e d i n the l i t e r a t u r e .  54. findings.  I n other words, where the r a t e o f a b s o r p t i o n  does  not appear t o be a f f e c t e d by l a c t o s e , changes i n the a b s o l u t e amount of n u t r i e n t a b s o r p t i o n The  c o u l d be  detected.  n u t r i t i o n a l i m p l i c a t i o n s t h a t can be drawn from  the balance s t u d i e s w i t h r a t s are not as s t r i k i n g as would be suggested by Paige and Graham (92) (33).  and Calloway and Chenoweth  Of course, one must e x e r c i s e c a u t i o n r.in e x t r a p o l a t i n g  from animal s t u d i e s t o humans. Finally,  i n any f u t u r e s t u d i e s , the l e v e l of l a c t o s e  administered to subjects  should be maintained w i t h i n the l i m i t s  of normal l a c t o s e consumption.  T h i s would a v o i d undue concern  over apparent n u t r i e n t l o s s e s due t o exaggerated l e v e l s of dietary lactose.  55.  V I I . SUMMARY A d u l t l a c t o s e i n t o l e r a n c e due t o low l a c t a s e l e v e l s i s o f t e n a s s o c i a t e d w i t h v a r y i n g degrees o f abdominal d i s t r e s s ranging  from b l o a t i n g and d i s t e n s i o n t o severe cramps and  diarrhea.  Recent s t u d i e s have suggested t h a t these g a s t r o -  i n t e s t i n a l disturbances  may i n t e r f e r e w i t h normal  of n u t r i e n t s i n a d d i t i o n t o l a c t o s e .  absorption  I n order t o i n v e s t i g a t e  t h i s p o s s i b i l i t y , both human and animal s t u d i e s were conducted. Twenty-three Caucasianst nine 3 1 years and  females between 2 1 and  o f age, mean = 2 5 years and f o u r t e e n males between 2 2  3 3 years  o f age, mean * 28 years were used t o study the  e f f e c t o f l a c t o s e on the a b s o r p t i o n o f v i t a m i n A, a s c o r b i c a c i d and p r o t e i n .  Lactose  t o l e r a n c e t e s t s r e v e a l e d t h a t 8 of  the s u b j e c t s were l a c t o s e i n t o l e r a n t on t h e b a s i s o f a maximal b l o o d glucose r i s e o f l e s s than 2 0 mg/ 1 0 0 ml over the f a s t i n g blood glucose  l e v e l and the presence o f g a s t r o i n t e s t i n a l  symptoms a f t e r a l a c t o s e t o l e r a n c e t e s t . samples were drawn a f t e r an o v e r n i g h t  I n each study,  blood  f a s t and a t i n t e r v a l s up  to 4 hours a f t e r consuming 5 0 g o f l a c t o s e i n an aqueous s o l u t i o n or t e s t meal c o n t a i n i n g g e l a t i n , v i t a m i n C or v i t a m i n A.  Sucrose r e p l a c e d l a c t o s e as a c o n t r o l . The r e s u l t s o f t h e human s t u d i e s f a i l e d t o demon-  s t r a t e t h a t l a c t o s e had an e f f e c t on t h e a b s o r p t i o n  of ascorbic  a c i d , v i t a m i n A or p r o t e i n i n l a c t o s e i n t o l e r a n t s u b j e c t s . mean maximum r i s e i n plasma u r e a ( 9 . 8 mg/100 ml), plasma  The  56.  ascorbic acid  ( 0 . 9 3 m g / 1 0 0 ml)  and plasma v i t a m i n A  1 0 0 ml) a f t e r l a c t o s e i n g e s t i o n d i d not d i f f e r (p> 0 , 0 5 ) (10.5  mg  (0.012  mg/  significantly  from the v a l u e s o b t a i n e d a f t e r consumption of sucrose u r e a / 1 0 0 ml,  vitamin A / 1 0 0 ml).  0.90  I t may  mg  ascorbic  acid/100  ml,  0.031  mg  be t h a t the composition of the t e s t  d r i n k which c o n t a i n e d f a t and p r o t e i n , may  have a f f e c t e d  the  r a t e of a b s o r p t i o n of those n u t r i e n t s through a d e l a y i n g a s t r i c emptying time.  However, the f i n d i n g t h a t a b s o r p t i o n  o f v i t a m i n C remained u n a f f e c t e d even when consumed w i t h an aqueous s o l u t i o n of l a c t o s e (without g e l a t i n ) ,  i s attributed  to the p o s s i b i l i t y t h a t , t h e l e v e l of a s c o r b i c a c i d g i v e n  was  too low t o show measurable d i f f e r e n c e s i n b l o o d l e v e l s of t h a t nutrient. I n order to study the e f f e c t of l a c t o s e on the a b s o r p t i o n of c a l c i u m , f a t and p r o t e i n , balance s t u d i e s were conducted  u s i n g postweaning r a t s .  The  experimental groups  r e c e i v e d e i t h e r 1 0 % , 2 0 % or 3 0 % l a c t o s e d i e t s , w h i l e an e q u i v a l e n t amount of sucrose r e p l a c e d the l a c t o s e i n the c o n t r o l diets. In a d d i t i o n , postweaning r a t s were g i v e n v i t a m i n A i n t r a g a s t r i c a l l y w i t h e i t h e r l a c t o s e or sucrose t o i n v e s t i g a t e the e f f e c t of l a c t o s e on v i t a m i n A a b s o r p t i o n . From the balance s t u d i e s w i t h r a t s , the r e s u l t s i n d i c a t e t h a t f e c a l n i t r o g e n and f a t e x c r e t i o n was cantly ( p < 0 . 0 5 )  h i g h e r i n a l l the animals  compared t o the c o n t r o l s . as p e r c e n t f a t i n t a k e was  signifi-  f e d l a c t o s e as  Mean f e c a l f a t e x c r e t i o n expressed 3.75%.  6 . 5 4 % and  4 . 4 3 % f o r those  57.  animals t h a t r e c e i v e d the 1 0 % , 2 0 % and 3 0 % l a c t o s e d i e t s r e s p e c t i v e l y , w h i l e the values were  2.30%,  3.42% and  S i m i l a r l y , mean f e c a l  3.51%.  e x c r e t i o n expressed as percent and  6.11%  f o r the corresponding c o n t r o l s  n i t r o g e n i n t a k e was  f o r the l a c t o s e groups and  3.71%.  3.68%  nitrogen 5.02%,  and  5.23%  4.22%  for  the c o n t r o l s on 1 0 % , 2 0 % and 3 0 % sucrose d i e t s , r e s p e c t i v e l y . However, f e c a l c a l c i u m  e x c r e t i o n was found t o be g e n e r a l l y  lower f o r each l a c t o s e group r e l a t i v e t o the c o n t r o l s , but t h e d i f f e r e n c e was s t a t i s t i c a l l y  significant  30% l e v e l of lactose intake.  The values  e x c r e t i o n as percent 28.20%  calcium  f o r each group on the  r e s p e c t i v e l y , and 51.42%,  i n t a k e were 10%,  44.05%  20%  and  (p<0.05)  only a t the  f o r mean f e c a l 45.12%,  and  30%  56.07%  calcium  3 8 . 1 4 % and  lactose diet  f o r the c o r r e s p o n -  ding c o n t r o l s . I t appears t h a t l a c t o s e impairs n i t r o g e n and f a t absorption, rats.  but enhances c a l c i u m a b s o r p t i o n  i n postweaning  Improved c a l c i u m a b s o r p t i o n may have important n u t r i -  t i o n a l i m p l i c a t i o n s where d i e t a r y c a l c i u m  intake i s low. 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I n f l u e n c e of t h e t h y r o i d gland on a b s o r p t i o n i n t h e d i g e s t i v e t r a c t . Amer. J . P h y s i o l . 123*577-588, 1938.  104.  Middleton, W.R.J.  12«172-177,  T h y r o i d hormones and the gut.  1971.  Gut  105.  M i d d l e t o n , W.R.J., and G.R. Thompson. The mechanism o f s t e a t o r r h e a i n induced h y p e r t h y r o i d i s m i n t h e r a t . J . Lab. C l i n . Med. 74t19-30, 1 9 6 9 .  106.  Matuchansky, C , P.M. Huet, J.Y. Mary, J.C. Rambaud and J . J . B e r n i e r . E f f e c t s o f c h o l e c y s t o k i n i n and raetoclopramide on j e j u n a l movements o f water and e l e c t r o l y t e s and on t r a n s i t time o f l u m i n a l f l u i d i n man.Eur. J. C l i n . In.  2*169-175. 1 9 7 2 .  107.  M o r i t z , M., G. F i n k e l s t e i n , H. Meshkinpour, J . F i n g e r u t and S.H. L o r b e r . 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G a s t r i c emptying. Amer. J . D i g . D i s . (NS) 7 * 6 7 2 - 6 7 6 , 1962.  114.  Sognen, E . E f f e c t s o f C a - b i n d i n g substances on g a s t r i c emptying as w e l l as i n t e s t i n a l t r a n s i t and a b s o r p t i o n i n i n t a c t r a t s . A c t a Pharmacol. T o x i c o l , 22t31-48, 1965.  The p a t t e r n o f g a s t r i c emptying. 182t144-149, 1966.  J . Physiol.  67.  115.  Kato, R., A. Takanaka, 0 . K i n i c h i and 0 . Yoshihito. E f f e c t of syrup on the absorption of drugs from g a s t r o i n t e s t i n a l t r a c t . Jap. J . Pharmacol. 19«331-342,  116.  Correia, J.P., and J.F.M. Nunes. Experimental studies on the absorption of I > 3 1 t r i o l e i n i n r a t s . Amer. J.  11?.  1969.  Dig.  Dis.  12il62-182,  1967.  Reynell, P.C, and G.H. Spray. The simultaneous measurement of absorption and t r a n s i t i n the gastroi n t e s t i n a l t r a c t of the r a t . J . P h y s i o l . 1 3 1 * 4 5 2 462,  1956.  118.  Pirk, F., I . Skala and M. Vulterinova. Milk intolerance a f t e r gastrectomy. Digestion 9 » 1 3 0 - 1 3 7 , 1 9 7 3 .  119.  Kocian,J.» M. Vulterinova, 0 . Bejblova and I. Skala. Influence of lactose intolerance on the bones of patients a f t e r p a r t i a l gastrectomy. Digestion 8i324-335.  120.  Wapnick, S. Milk and lactose intolerance following d i s t a l small bowel resection. Amer. J . C l i n . Nutr. 25i655-660,  121.  1973.  1972.  Kocian, J . , I. Skala and K. Bakos. Calcium absorption from milk and lactose free milk i n healthy subjects and patients with lactose intolerance. Digestion 9*317-324,  1973.  122.  Stephenson, L.S., and M.C Latham. Lactose intolerance and milk consumption* the r e l a t i o n of tolerance to symptoms. Amer. J . C l i n . Nutr. 2 7 * 2 9 6 - 3 0 3 , 1974,  123.  Bayless, T.M., and D.M. Paige. Disaccharide intolerance in feeding programs. In* Proc. Western Hemisphere Nutr. Congr. III. . ed. P.L. White. Mount Kisco, N.Y. Futura, 1 9 7 2 . p. 1 8 8 - 1 9 6 . r  124.  Reddy, V., and J . Pershad, Lactase deficiency i n Indians. Amer. J . C l i n . Nutr. 2 5 » 1 1 4 - 1 1 9 , 1972.  125.  Leichter, J . Comparison of whole milk and skim milk with aqueous lactose s o l u t i o n i n lactose tolerance t e s t i n g . Amer. J . C l i n . Nutr. 2 6 * 3 9 3 - 3 9 6 , 1 9 7 3 .  126.  Bedine, M.S., and T.M. Bayless. Modification of lactose • 1 tolerance by glucose or a meal. C l i n . Res. 20*448, 1972. (Abstract)  68. 127*  Paige, D.M., £ . Leonardo, J . Nakashima, B. A d r i a n z e n T . and G.G. Graham, Response o f l a c t o s e i n t o l e r a n t c h i l d r e n t o d i f f e r e n t l a c t o s e l e v e l s . Amer. J . C l i n . Nutr. 25i467-469, 1972.  128.  Bedine, M.S., and T.M. B a y l e s s . I n t o l e r a n c e of s m a l l amounts o f l a c t o s e by i n d i v i d u a l s w i t h low l a c t a s e l e v e l s . G a s t r o e n t e r o l o g y 65i735-743, 1973.  129.  Garza, C., Y, Garza, C. Pass and N.S. Scrimshaw. Lack o f symptoms from normal m i l k consumption i n l a c t o s e i n t o l e r a n t c h i l d r e n . Fed. P r o c . 33«684, 1974. ( A b s t r a c t s from 58th annual meeting, A t l a n t i c C i t y , N.J., A p r i l , 1974.)  130.  S k a l a , I . , and V. Lamacova. D i e t s i n l a c t o s e i n t o l e r a n c e . Nutr. Metabol. 131200-206, 1971.  131.  Eggum, B , 0 . Blood u r e a measurement as a technique f o r assessing protein quality. B r i t . J . Nutr. 24«983988, 1970.  132.  Wiseman, G. A b s o r p t i o n from the i n t e s t i n e . Acad. P r e s s , 1964.  133.  Barrowman, J.A., A. D f M e l l o and A. Herxheimer. A s i n g l e dose o f neomycin impairs a b s o r p t i o n o f v i t a m i n A ( r e t i n o l ) i n man. Eur. J . C l i n . Pharmacol. 5«199-202,  Londoni  1973.  134.  The e n z y m a t i c / c o l o r i m e t r i c d e t e r m i n a t i o n o f g l u c o s e i n whole b l o o d , plasma or serum a t 425-475 mu, per Sigma T e c h n i c a l B u l l e t i n #510 purchased from Sigma Chemical Co., S t . L o u i s , Miss. M o d i f i c a t i o n o f Raabo, E., and T.C. T e r k i l d s e n . On the enzymatic d e t e r m i n a t i o n o f b l o o d g l u c o s e . Scand. J . C l i n . Lab. I n v e s t . 12»402407. I960.  135.  F o r c o l o r i m e t r i c d e t e r m i n a t i o n of u r e a n i t r o g e n , preformed ammonia i n u r i n e and blood n o n p r o t e i n n i t r o g e n . Hyland L i s t No. 0 3 0 - 0 1 0 . Purchased from Hyland, D i v . T r a v e n o l L a b o r a t o r i e s , Inc., C o s t a Mesa, C a l i f .  136.  Manual f o r n u t r i t i o n s u r v e y s . I n t e r d e p a r t m e n t a l committee on n u t r i t i o n f o r n a t i o n a l defence. Bethesda, M.D. 1963. Plasma or serum v i t a m i n A and c a r o t e n e - C a r r P r i c e Method, p. 124-128.  137.  Roe, J.H., and C.A. Kuether. The d e t e r m i n a t i o n o f a s c o r b i c a c i d i n whole blood and u r i n e through the 2 , 4 - d i n i t r o phenylhydrazine d e r i v a t i v e of dehydroascorbic a c i d . J . B i o l . Chem. 147O99-407, 1943.  69.  138.  Bradstreet, R.B. The Kjeldahl method f o r organic nitrogen. N.Y* Acad. Press, 1 9 6 5 .  139.  W i l l i s , J.B. Determination of calcium and magnesium i n urine by atomic absorption spectroscopy. Anal. Chem, 33*556-559.  1961.  140.  Zettner, A., and D. Seligson. A p p l i c a t i o n of atomic absorption spectrophotometry i n the determination of calcium i n serum. C l i n . Chem. I G 1 8 6 9 - 8 9 0 , 1964.  141.  Pomeranz, X., and C.E. Meloan. Food analysis* theory and practice. Westport, Conn.* A v i Publ. Co., 1971.  142.  Medler, E.M., L.W. Jacobs, K.R. Bailey and L.A. Sheffner. N u t r i t i o n a l evaluation of high lactose formulas i n the r a t . Fed. Proc. 25*606, 1 9 6 6 . (Abstract)  143.  Pansu, D., and M.C. Chapuy. Calcium absorption enhanced by lactose and xylose. C a l c i f . Tissue Res. 4 (supp)i 155-156,  144.  1970.  Lengemann, F.W. The s i t e of action of lactose i n the enhancement of calcium u t i l i z a t i o n . J . Nutr. 69*232?,  1959.  145.  Finlayson, B. Lactose and i n t e s t i n a l absorption of calcium. Invest. U r o l . 7*433-441, 1970.  146.  Vaughan, O.W., and L.J. F i e r , The enhancing action of c e r t a i n carbohydrates on the i n t e s t i n a l absorption of calcium i n the r a t . J . Nutr. 71*10-14, i960.  147.  Wasserman, R.H., and F.W. Lengemann, Further observations on lactose stimulation of the g a s t r o i n t e s t i n a l absorpt i o n of calcium and strontium i n the r a t . J . Nutr. 70*377-383. I960.  70.  A  P  P  E  N  D  I  X  Table I .  Maximum r i s e i n plasma u r e a i n l a c t o s e t o l e r a n t and i n t o l e r a n t s u b j e c t s g i v e n 5 5 g g e l a t i n and 2 5 , 0 0 0 IU v i t a m i n A w i t h e i t h e r 5 0 g l a c t o s e or 5 0 g s u c r o s e .  Subject No.  (mg urea Lactose  /  1 0 0 ml) sucrose  1.  9.6  9.9  2.  16.1  12.2  3.  7.5  11.1  4.  8.2  12.9  5.  20.6  12.6  6.  13.5  7.9  7.  6.2  5.4  Lactose Tolerant  1  Mean + S.D.  Lactose Intolerant  11.7  +  5.57  10.3  ±  8.  9.4  8.4  9.  6.5  6.4  10.  7.5  5.8  11.  11.0  16.4  12.  14.5  15.3  Mean + S.D.  9.8  +  3.16  10.5  +  2.78  5.03  72.  Table I I .  Maximum r i s e i n plasma a s c o r b i c a c i d i n l a c t o s e t o l e r a n t and i n t o l e r a n t s u b j e c t s g i v e n 5 0 0 mg v i t a m i n G and 2 5 . 0 0 0 IU v i t a m i n A w i t h e i t h e r 5 0 g l a c t o s e or 5 0 g s u c r o s e .  •  Subject No.  Lactose Tolerant  1  0.75  0.93  2  0.96  0.98  3  1.3?  0.82  4  1.17  1.49  5  1.14  1.18  6  0.49  0.70  Mean + S.D.  Lactose Intolerant  Mean + S.D.  (mg v i t a m i n C / 100ml) Lactose Sucrose  0.97  + 0.31  1.02 + 0.28  7  1.00  1.29  8  0.69  0.49  9  1.09  0.93  0.93  + 0.21  0.90 + 0.40  Table I I I .  Maximum r i s e i n plasma a s c o r b i c a c i d i n l a c t o s e i n t o l e r a n t s u b j e c t s g i v e n 200,000 IU v i t a m i n A, 1 g v i t a m i n C and a t e s t meal c o n t a i n i n g 15 g c a s i l a n , 25 ml o l i v e o i l w i t h e i t h e r 45 g l a c t o s e or 45 g s u c r o s e .  Subject No.  mg v i t a m i n C / 100 ml Lactose  Sucrose  1  0.98  1.13  2  1.05  0.71  3  1.07  1.25  4  1.09  1.03  1 . 0 5 + 0.048  1 . 0 3 + 0.232  Mean + S.D.  74.  T a b l e IV.  Maximum r i s e i n plasma v i t a m i n A i n l a c t o s e i n t o l e r a n t s u b j e c t s g i v e n 2 0 0 , 0 0 0 IU v i t a m i n A, 1 g v i t a m i n C and a t e s t meal c o n t a i n i n g 1 5 g c a s i l a n , 2 5 ml o l i v e o i l with; e i t h e r 4 5 g l a c t o s e or 4 5 g s u c r o s e .  Subject No.  mg v i t a m i n A / 1 0 0 ml Lactose Sucrose  1  0.009  0.048  2  0.014  0.012  3  0.023  0.055  4  0.003  0.009  Mean +  S.D,  0.012  +  0.00855  0.031  +  0.0239  20 Time  (minutes)  FIGURE 1.  Mean P l a s m a U r e a L e v e l s i m L a c t o s e T o l e r a n t (LT) and S I n t o l e r a n t S u b j e c t s G i v e n 55 g G e l a t i n W i t h E i t h e r 50 g L a c t o s e (L) o r 50 g S u c r o s e ( S ) .  u  (LI)  LT LT LI LI  Time FIGURE 2  (minutes)  Mean P l a s m a A s c o r b i c A c i d L e v e l s i n f c L a c t o s e T o l e r a n t (LT) and 3 I n t o l e r a n t ( L I ) S u b j e c t s G i v e n 500 mg V i t a m i n C and 25,000 IU V i t a m i n A W i t h E i t h e r 50 g L a c t o s e (L) o r 50 g S u c r o s e ( S ) .  (S) (L) (L) (S)  3.00  e o o  Time  (minutes)  Mean P l a s m a A s c o r b i c A c i d L e v e l s i n L a c t o s e I n t o l e r a n t fa) S u b j e c t s G i v e n 2 00,000 IU V i t a m i n A and 1 g Vitamin C W i t h a T e s t M e a l C o n t a i n i n g 15 g C a s i l a n , 25 ml O l i v e O i l and E i t h e r 45, g ' L a c t o s e o r 45 g S u c r o s e .  0.07  Sucrose  0.06 + o o  •ri  e -p  0.05 4 Lactose  •ri  >  e 0.04  0.03 240 Time FIGURE' 4,  (minutes)  Mean P l a s m a V i t a m i n A L e v e l s i n L a c t o s e I n t o l e r a n t S u b j e c t s (4) G i v e n 200,000 IU V i t a m i n A and 1 g V i t a m i n C W i t h a T e s t M e a l C o n t a i n i n g 15 g C a s i l a n and 25 ml O l i v e O i l and E i t h e r 45 g L a c t o s e o r 45 g S u c r o s e .  00  .300.  Time FIGURE  (hours)  5. Mean P l a s m a V i t a m i n A L e v e l s i n R a t s A f t e r I n t r a g a s t r i c A d m i n i s t r a t i o n o f 500 mg L a c t o s e o r 500 mg S u c r o s e , and 2500 IU V i t a m i n A. (M « 3 0  

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