Metabolism and Physiological Effects of the Polyols (Alditols)

Downloaded by UNIV OF CALIFORNIA SAN DIEGO on September 14, 2014 | http://pubs.acs.org Publication Date: June 1, 1975 | doi: 10.1021/bk-1975-0015.ch007

7 Metabolism and Physiological Effects of the Polyols (Alditols) OSCAR TOUSTER Department of Molecular Biology, Vanderbilt University, Nashville, Tenn. 37235

I. Introduction Polyols, or alditols, are of course not strictly carbohydrates, but since they are produced chemically and biologically from sugars, we can consider them honorary carbohydrates. They are now established in mammalian metabolism and are of some importance in nutrition and pathology. In this paper I survey the roles of polyols and emphasize some of the most pertinent current uses and problems. II. Survey of the Occurrence and Enzymology of the Polyols The occurrence of polyols in animals is summarized in Table I. TABLE I. POLYOLS IN ANIMAL METABOLISM Occurrence in tissues Sorbitol—fetal blood, seminal vesicles and plasma, nerve, lens of alloxan-diabetic rats or rats given cataractogenic dose of D-xylose Xylitol—lens of rats given cataractogenic dose of D-xylose Dulcitol—various tissues after cataractogenic dose of D-galactose Occurrence in urine Erythritol D-arabitol, L-arabitol Sorbitol D-mannitol Utilization by mammals in vivo High--xylitol, ribitol, sorbitol Variable--D-mannitol (oral dose moderately utilized; parenteral--poorly) Poor--arabitol (D andL),dulcitol 123 In Physiological Effects of Food Carbohydrates; Jeanes, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1975.


124

PHYSIOLOGICAL

EFFECTS

O F FOOD

CARBOHYDRATES

S o r b i t o l i s most widely d i s t r i b u t e d , o c c u r r i n g in fetal blood and in seminal v e s i c l e s and plasma, where the p o l y o l is un doubtedly a normal metabolic intermediate. S o r b i t o l accumulates i n some t i s s u e s of d i a b e t i c animals, a matter which is discussed i n greater d e t a i l below. X y l i t o l and, to a smaller extent, sor bitol accumulate in the lens of r a t s given c a t a r a c t o g e n i c doses of Πτ-xylose (1). D u l c i t o l , or galactitol, accumulates a f t e r c a t aractogenic doses of D-galactose, and it is a l s o found i n the human genetic d i s e a s e , galactosemia. Several p o l y o l s have been i s o l a t e d from human u r i n e : e r y t h r i t o l (2), a r a b i t o l (3), mannitol and s o r b i t o l (4,5). The utilization of p o l y o l s by mammals is a l s o i n d i c a t e d i n Table I, with the wide range of utilization i n d i c a t e d . The most a p p r e c i a b l y used p o l y o l s are xylitol, ribitol, and s o r b i t o l . The main biochemical r e a c t i o n s of p o l y o l s a r e shown below:

Enzymatic

Reactions of P o l y o l s

General

Polyol

Mammals a

L-Xylulose

D-Glucose ^

b

s

s

xylitol

sorbitol

a

a

s

D-xylulose

*D-fructose

P o l y o l s undergo o x i d a t i o n to the corresponding ketose (a) or to the corresponding aldose ( b ) , or phosphorylation to the p o l y o l 1-phosphate ( c ) . Many examples of r e a c t i o n s (a) and (b) a r e found i n mammals. The L - x y l u l o s e - x y l i t o l - D ^ x y l u l o s e i n t e r c o n v e r s i o n occurs i n the g l u c u r o n a t e - x y l u l o s e c y c l e . The glucoses o r b i t o l - f r u c t o s e i n t e r c o n v e r s i o n occurs i n male accessory organs and undoubtedly i n other t i s s u e s as w e l l . However, the phos p h o r y l a t i o n of p o l y o l s occurs i n microorganisms but not i n mam mals. A review on p o l y o l s w i l l supply the reader with a d d i t i o n a l information i n t h i s biochemical area ( 6 ) .

In Physiological Effects of Food Carbohydrates; Jeanes, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1975.

7.

III.

125

Polyols (Alditols)

TOUSTER

X y l i t o l i n Metabolism and N u t r i t i o n

Many years ago, when we were i n v e s t i g a t i n g the metabolism of L r x y l u l o s e , the sugar excreted i n gram q u a n t i t i e s by humans w i t h the genetic metabolic abnormality known as e s s e n t i a l p e n t o s u r i a , we discovered that ^ - x y l u l o s e i s normally u t i l i z e d as shown i n the f o l l o w i n g equations:


CH.OH \

CH.OH I

2

0 0

1

HCOH I HOCH » CH OH

NADPH

ΝADP

1

HOCH I HCOH ο I HOCH CH OH 2

L-Xylulose

CH 0H I HCOH I HOCH I

NAD

NADH

HCOH I CH OH

D-Xylulose

Xylitol CH 0H I HCOH o 2

I

CH 0H ! C=0 I HOCH I HCOH I CH OH o 2

o 1

CH 0H I HCOH o 2

\

HCOH I

HOCH I

CH OH

HOCH I HOCH I CH OH

L-Arabitol

The J±-xylulose i s reduced t o x y l i t o l by an u n u s u a l l y s p e c i f i c NADPH-linked p o l y o l dehydrogenase (7,8) . The x y l i t o l i s then r e o x i d i z e d t o D-xylulose by an NAD-linked enzyme of r a t h e r broad but d e f i n i t e s p e c i f i c i t y . This enzyme i s most commonly known as s o r b i t o l dehydrogenase. P e n t o s u r i c i n d i v i d u a l s excrete smaller amounts o f L - a r a b i t o l , probably as a " d e t o x i c a t i o n " product of the accumulated L - x y l u l o s e . The s u b s t r a t e s p e c i f i c i t y of s o r b i t o l dehydrogenase, which i s b e t t e r expressed by the name, J v - i d i t o l dehydrogenase, i s shown below: S o r b i t o l dehydrogenase i s s p e c i f i c f o r erythro-1,2,4-polyol c o n f i g u r a t i o n .

CH OH 2

hOH hOH



126

PHYSIOLOGICAL

EFFECTS

OF

FOOD

CARBOHYDRATES

As can be seen from the formula on the r i g h t , s o r b i t o l , x y l i t o l , and r i b i t o l are good s u b s t r a t e s . The low l e v e l of o x i d a t i o n of L - a r a b i t o l by t h i s enzyme even when h i g h l y p u r i f i e d has not been explained. The work on L - x y l u l o s e metabolism i n our l a b o r a t o r y and of King, Burns and others on L-ascorbic a c i d b i o s y n t h e s i s l e d to the formulation of the glucuronate-xylulose c y c l e (9,10), which i s shown i n F i g u r e 1. This c y c l e occurs i n a l l mammals i n which i t has been studied, the r e a c t i o n s g e n e r a l l y o c c u r r i n g i n the l i v e r and i n the kidney. The f u n c t i o n of the c y c l e i s not completely understood. Since an i n a b i l i t y to c a r r y out the r e d u c t i o n of J±x y l u l o s e to x y l i t o l i s apparently not d e l e t e r i o u s , pentosuria i s an i n h e r i t e d metabolic d i s o r d e r (11,12), not a metabolic d i s e a s e . The e a r l y r e a c t i o n s i n the c y c l e are obviously important. I t appears that most higher animals b i o s y n t h e s i z e L r a s c o r b i c a c i d , although primates, the guinea p i g , f l y i n g mammals, and i n s e c t s (13) do not. I t has been demonstrated that man, the monkey, and the guinea p i g l a c k the l i v e r microsomal oxidase that converts L-gulonolactone to the keto d e r i v a t i v e . I would a l s o point out the numerous o x i d a t i o n - r e d u c t i o n s using p y r i d i n e n u c l e o t i d e l i n k e d coenzymes which e f f e c t i v e l y move hydrogen from NADPH to NAD, thereby p o s s i b l y serving a transhydrogenase f u n c t i o n . I should a l s o mention that although i t i s accepted that UDP-glucose and UDP-glucuronate are e a r l y members of the c y c l e , and obviously serve as precursors of sugar moieties i n glyco-polymers, there i s some u n c e r t a i n t y as to how the f r e e glucuronate i s produced. Since, i n the conversion of glucuronate to I±-xylulose v i a L-gulonate, there occurs a decarboxylation of the C5 carbon of glucuronate, t h i s carbon being the same as of glucose, t h i s c y c l e can be considered a o x i d a t i o n pathway f o r glucose. It may then be asked whether much glucose i s o x i d i z e d normally through t h i s pathway. S p e c i f i c studies i n d i c a t e that only a small amount of glucose i s handled v i a t h i s route. From the f a c t that pentosuric i n d i v i d u a l s normally excrete s e v e r a l grams of Lr x y l u l o s e each day and from experiments on the extent of augmenta t i o n of t h i s e x c r e t i o n on feeding the precursor Ιλ-glucuronolactone, i t can be estimated that the carbohydrate f l u x through the c y c l e i s between 5 and 15 grams per day (14). I t was t h e r e f o r e of some i n t e r e s t that Winegrad and h i s a s s o c i a t e s reported s e v e r a l years ago that the o x i d a t i o n of glucose i s enhanced i n a l l o x a n - d i a b e t i c r a t s (15) and that L r x y l u l o s e l e v e l s i n the serum of d i a b e t i c humans are s e v e r a l times higher than normal (16). These f i n d i n g s are not w e l l understood. I t does appear, however, that i n diabetes the s o - c a l l e d i n s u l i n dependent pathways are more prominently employed and that more glucose appears to be o x i d i z e d v i a glucuronate and v i a s o r b i t o l , as w i l l be discussed i n more d e t a i l below. The u t i l i z a t i o n of p o l y o l s became of s p e c i a l i n t e r e s t when the metabolic importance of s o r b i t o l and x y l i t o l was discovered. The high conversion of an administered p o l y o l to l i v e r glycogen


7.

TOUSTER

127

Poly oh (Alditols)

L- Ascorbic Acid


- Keto-L-gulonoloctone L- Gulonolactone

?

ÇH OH

H0 :OH OH

2

(SOT

I

HCOH HOCH I HCOH I HCOH

HOCH HCOH I HCOH

AojH

C0 H

Ο

Ç0 H 2

HOÇH HOC H HCOH I HOCH £Η ΟΗ

[NAD]

2

2

UDP- glucuronote

0-Glucuronate

L- Gulonote

C0 H 2

HOCH I

?-°

HCOH

UOP-glucose

HOCH -Keto-LCH OHgulonote 2

Glycogen-

• C0

^Hexose phosphate ( pentose ^\ phosphate \V pathway) \ *

2

C-0 HCOH

CH 0H

HOCH CH OH

2

C-0 HOCH I HCOH I CH OP03H 2

2

CH OH

2

L-Xylulose 4L 1NADPH| 2

CH 0H

D-Xylulose \ ^ 5-phosphate

2

i-o

A O P ^ ^ HOCH A

T

P

HCOH

C H OH

the major route of u t i l i z a t i o n of administered sorbitoI^sHknown:

Route of U t i l i z a t i o n of S o r b i t o l and Fructose CH 0(f) 2

CH 0H

CH 0H

o

2

C=0 HCOH ι HOCH ι HCOH

I

C 0 I

CH OH

HOCH

-> F - l - P

HCOH

I

I

CHO I

HCOH

HCOH ι CH 0H

I

HCOH _ I

CH OH

2

CH 0H 2

Sorbitol

CHO I

CHOH C H O ®

D-Fructose

S o r b i t o l i s o x i d i z e d to f r u c t o s e , which i s then phosphorylated to fructose-l-phosphate followed by cleavage to dihydroxyacetone phosphate and glyceraldehyde. The l a t t e r i s then phosphorylated to the 3-phosphate. Both t r i o s e phosphates are members of the Embden-Meyerhof g l y c o l y t i c pathway. Gabbay (33) has r e c e n t l y observed another metabolic i n t e r r e l a t i o n s h i p between f r u c t o s e and h e x i t o l s . Dietary fructose i s converted, i n about 3% y i e l d , t o u r i n a r y ^-mannitol. He has presented evidence that the enzyme aldose reductase s u r p r i s i n g l y has the c a p a c i t y to c a t a l y z e t h i s r e d u c t i o n of f r u c t o s e to mannitol. S o r b i t o l i s i n f a c t an important metabolic intermediate as shown below:

n

n

1

NADPH. _ , , -. NAD Sorbitol

v

D-Glucose

v

(aldose reductase)

^-Fructose

(sorbitol dehydrogenase)

The s o r b i t o l pathway (34,35) i n v o l v e s the conversion of glucose to s o r b i t o l through the mediation of the enzyme aldose reductase,



7.

TOUSTER

Polyols (Alditols)

131

with NADPH as coenzyme. S o r b i t o l i s o x i d i z e d to D-fructose by s o r b i t o l dehydrogenase. There i s some evidence that t h i s pathway of glucose u t i l i z a t i o n , as w e l l as the g l u c u r o n i c - x y l u l o s e c y c l e , are somewhat more e x t e n s i v e l y u t i l i z e d during i n s u l i n d e f i c i e n c y (35). Should glucose enter c e l l s i n higher amount than usual and be converted to s o r b i t o l and f r u c t o s e , which are p o o r l y permeable, osmotic changes may occur which are u n d e s i r a b l e . The evidence i s strong that t h i s sequence of events i s involved i n the production of d u l c i t o l from galactose i n the lens and the formation of c a t a r a c t i n i n d i v i d u a l s with galactosemia (1,36). Gabbay (37) has emphasized that p o l y o l accumulation i n nerve may be r e l a t e d to the occurrence of d i a b e t i c neuropathy. For example, galactosemia causes increases i n nerve d u l c i t o l and water content, and decreases the motor nerve conduction v e l o c i t y . If the animals are then placed on a normal d i e t , the d u l c i t o l and water content decrease, and the nerve conduction v e l o c i t y i s r e s t o r e d to normal. Moreover, a r t i f i c i a l l y - i n d u c e d diabetes i n the r a t causes an increase i n s o r b i t o l and f r u c t o s e as w e l l as i n glucose i n p e r i p h e r a l nerve. A decrease i n the nerve conduction v e l o c i t y occurs c o n c u r r e n t l y . In an attempt to modify these events, Gabbay, Dvornik, and t h e i r a s s o c i a t e s have been studying s y n t h e t i c i n h i b i t o r s of aldose reductase as p o s s i b l e agents f o r b l o c k i n g p o l y o l formation i n animals. A recent report demons t r a t e s that the i n h i b i t o r AY22284 reduces the accumulation of g a l a c t i t o l i n both the lens and s c i a t i c nerve of galactosemic r a t s , g r e a t l y reduces and delays the formation of d e t e c t a b l e c a t a r a c t s i n g a l a c t o s e - f e d r a t s , and reduces the accumulation of s o r b i t o l and of f r u c t o s e , but not of glucose, i n the s c i a t i c nerve of a r t i f i c i a l l y - d i a b e t i c r a t s (38) . Of course, l i t t l e work has been done on the human i n t h i s area, and there w i l l be continued d i f f i c u l t i e s i n doing such i n v e s t i g a t i o n s on human d i a b e t i c s . A cause and e f f e c t r e l a t i o n s h i p between p o l y o l accumulation i n nerve and decrease i n f u n c t i o n has not been d e f i n i t e l y establ i s h e d even i n experimental animals, and even i f t h i s were to be accomplished, i t would s t i l l remain to be determined whether d i a b e t i c neuropathy i n the human has the same cause. The moderate, and dose dependent, u t i l i z a t i o n of o r a l l y administered mannitol, and the e f f e c t s of t h i s h e x i t o l on i n t e s t i n a l f u n c t i o n , have been e x t e n s i v e l y studied (39) . The use of mannitol as a d i u r e t i c agent has r e c e n t l y been reviewed (40). V.

M a l t i t o l and

Isomaltitol

M a l t i t o l has been studied r e c e n t l y at Charles P f i z e r and Company because of r e p o r t s that t h i s p o l y o l i s low c a l o r i c and t h e r e f o r e might be a superior sweetening agent (41 ,42) . Dr. H. H. Rennard of P f i z e r has informed me of h i s work, some of which was done i n c o l l a b o r a t i o n with Dr. J. R. Bianchine of Johns Hopkins. The low recovery of administered l a b e l e d m a l t i t o l i n the u r i n e and feces of the r a t i n d i c a t e d that i t was e f f i c i e n t l y


132

PHYSIOLOGICAL

EFFECTS

O F FOOD

CARBOHYDRATES

u t i l i z e d , and s i m i l a r l y encouraging r e s u l t s were obtained i n the human, i n c l u d i n g high recovery of -^C i n expired CO2. However, the f a c t that the expired 0 ^0 peak i n r a t s occurred a t 4 t o 5 hours a f t e r feeding suggested that the l a b e l might have been ab sorbed i n the lower gut. I t was indeed found that the m a l t i t o l was being u t i l i z e d by i n t e s t i n a l m i c r o f l o r a , which apparently were converting the l a b e l e d p o l y o l i n t o v o l a t i l e f a t t y a c i d s . In a d d i t i o n , i n t e s t i n a l mucosal preparations of r a t s have a low c a p a c i t y to hydrolyze m a l t i t o l . Therefore, although the u t i l i z a t i o n of the m a l t i t o l i s i n d i r e c t , i n v o l v i n g i t s p r e l i m i n a r y con v e r s i o n to f a t t y a c i d s , t h i s p o l y o l i s considered by Rennard t o be a w e l l u t i l i z e d substance. The u t i l i z a t i o n of i s o m a l t i t o l has a l s o been i n v e s t i g a t e d . From studies on r a t s i t was suggested that i t could be a u s e f u l i n g r e d i e n t i n c a l o r i e - r e d u c e d foods and beverages (43). 1Ζ


2

VI.

Concluding Remarks

At the present time s o r b i t o l and x y l i t o l are the most impor tant a l d i t o l s i n that they are key metabolic intermediates and are being fed or administered t o humans i n considerable amounts. As f a r as the f u t u r e i s concerned, i t appears to me that the problems which w i l l most a c t i v e l y concern i n v e s t i g a t o r s are r e l a t e d t o the more general use of x y l i t o l , f u r t h e r i n v e s t i g a t i o n of the p o s s i b l e r o l e of s o r b i t o l i n diabetes, and the p o s s i b l e advantages of p o l y o l s i n decreasing d e n t a l c a r i e s . Literature Cited

1. van Heyningen, R., in "Proceedings of the International Sym posium on Metabolism, Physiology, and Clinical Use of Pentoses and Pentitols," Hakone, Japan, August 27-29, 1967 (B. L. Horecker, K. Lang, and Y. Takagi, eds.), pp. 109123, Springer-Verlag, Berlin, Heidelberg, New York (1969). 2. Touster, O., Fed. Proc. (1960) 19, 977-983. 3. Touster, O. and Harwell, S., J. Biol. Chem. (1958) 230, 1031-1041. 4. Pitkänen, E. and Pitkänen, Α., Ann. Med. Exp. Fenn. (1964) 42, 113-116. 5. Ingram, P., Applegarth, D. Α., Sturrock, S., and Whyte,J.N. C., Clin. Chim. Acta (1971) 35, 523-524. 6. Touster, O. and Shaw, D. R. D., Physiol. Rev. (1962) 42, 181225. 7. Hollmann, S. and Touster, O., J. Biol. Chem. (1957) 225, 87102. 8. Arsenis, C. and Touster, O., J. Biol. Chem. (1969) 244, 38953899. 9. McCormick, D. B. and Touster, O., J. Biol. Chem. (1957) 229, 451-461.



7.

TOUSTER

Polyols

(Alditols)

133

10. Burns, J. J. and Kanfer, J., J. Am. Chem. Soc. (1957) 79, 3604-3605. 11. Touster, O., Fed. Proc. (1960) 19, 977-983. 12. Hiatt, H. H., in "The Metabolic Basis of Inherited Disease" (J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, eds.), third ed., pp. 119-130, McGraw-Hill, New York (1972). 13. Gupta, S. D., Chaudhuri, C. R., and Chatterjee, I. B., Arch. Biochem. Biophys. (1972) 152, 889-890. 14. Hollmann, S. and Touster, O., "Non-glycolytic Pathways of the Metabolism of Glucose," p. 107, Academic Press, New York (1964). 15. Winegrad, A. I. and Shaw, W. Ν., Am. J. Physiol. (1964) 206, 165-168. 16. Winegrad, A. I. and Burden, C. L., New Engl. J. Med. (1966) 274, 298-305. 17. McCormick, D. B. and Touster, O., Biochim. Biophys. Acta (1961) 54, 598-600. 18. Horecker, B. L., Lang, Κ., and Takagi, Y., eds., "Proceed ings of the International Symposium on Metabolism, Physiology, and Clinical Use of Pentoses and Pentitols," Hakone, Japan, August 27-29, 1967, Springer-Verlag, Berlin, Heidelberg, New York (1969). 19. Lang, K. and Fekl, W., Z. Ernährungswissenschaft (1971) Suppl. 11. 20. Sipple, H. L. and McNutt, K. W., eds., "Sugars in Nutrition," Academic Press, New York, San Francisco, London (1974). 21. Förster, H., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 259-280, Academic Press, New York, San Francisco, London (1974). 22. Froesch, E. R. and Jakob, Α., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 241-258, Academic Press, New York, San Francisco, London (1974). 23. Meng, H. C., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 527-566, Academic Press, New York, San Francisco, London (1974). 24. Thomas, D. W., Edwards, J. B., and Edwards, R. G., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 567-590, Academic Press, New York, San Fran cisco, London (1974). 25. van Eys, J., Wang, Y. M., Chan, S., Tanphaichitr, V. S., and King, S. M., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 613-631, Academic Press, New York, San Francisco, London (1974). 26. Thomas, D. W., Edwards, J. B., Gilligan, J. E., Lawrence, J. R., and Edwards, R. G., Med. J. Australia (1972) 1, 12381246. 27. Brin, M. and Miller, O. N., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 591-606, Academic Press, New York, San Francisco, London (1974).



134

PHYSIOLOGICAL EFFECTS OF FOOD CARBOHYDRATES

28. Grunberg, E., Beskid, G., and Brin, M., Int. J. Vitamin and Nutrition Res. (1973) 43, 227-232. 29. Mäkinen, Κ. Κ., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 645-687, Academic Press, New York, San Francisco, London (1974). 30. Bässler, Κ. H., in "Proceedings of the International Sympo sium on Metabolism, Physiology, and Clinical Use of Pentoses and Pentitols," Hakone, Japan, August 27-29, 1967 (B. L. Horecker, K. Lang, and Y. Takagi, eds.), pp. 190-196, Springer-Verlag, Berlin, Heidelberg, New York (1969). 31. Hers, H. G., Biochim. Biophys. Acta (1960) 37, 127-138. 32. Hue, L. and Hers, H.-G., Eur. J. Biochem. (1972) 29, 268275. 33. Gabbay, Κ. H., Clin. Research (1974) XXII (3), 468A. 34. Hers, H. G., Biochim. Biophys. Acta (1956) 22, 202-203. 35. Winegrad, A. I., Clements, R. S., and Morrison, A. D., in "Handbook of Physiology," (Amer. Physiol. Soc.,J.Field, ed.), Sect. 7, Vol. I, pp. 457-471, Williams & Wilkins, Baltimore, Maryland (1972). 36. Kinoshita, J. H., Invest. Ophthalmol. (1965) 4, 786-799. 37. Gabbay, Κ. H., New Engl. J. Med. (1973) 288, 831-836. 38. Dvornik, D., Simard-Duquesne, N., Krami, M., Sestanj, Κ., Gabbay, Κ. H., Kinoshita, J. H., Varma, S. D., and Merola, L. O., Science (1973) 182, 1146-1147. 39. Nasrallah, S. M. and Iber, F. L., Am. J. Med. Sci. (1969) 258, 80-88. 40. Ginn, Η. Ε., in "Sugars in Nutrition" (H. L. Sipple and K. W. McNutt, eds.), pp. 607-612, Academic Press, New York, San Francisco, London (1974). 41. Naito, F., New Food Industry (1971) 13, 1. 42. Hosoya, Ν., Ninth Internat. Congr. Nutrition (1972) Mexico. 43. Musch, K., Siebert, G., Schiweck, H., and Steinle, G., Z. Ernährungswissenschaft (1973), Suppl. 15, pp. 3-16.


Metabolism and Physiological Effects of the Polyols (Alditols)

Recommend Documents