Clin. Bioehem. 9, (3) 141-143 (1976)

Xylose Absorption and Its Clinical Significance J. T. HINDMARSH

Division of Clinical Chemistry, Nova Scotia Pathology Institute, and Department of Pathology, Dalhousie University, Halifax, Nova Scotia B3H 1V8

CLBIA, 9, (3) 141-143 (1976) Clin. Biochem.

Hindmarsh, J. T.

Division of Cliuical Chemistry, Nova Scotia Pa- thology Instih~te, and Department of Pathology, Dalhousie University, Halifax, N.S. B3H IV8

XYLOSE ABSORPTION AND ITS CLINICAL SIGNIFICANCE

1. Xylose absorption by the small intestine proba- bly includes an active process.

2. For xylose testing, the 25-g dose appears to be preferable to 5 g.

3. Factors that influence the test result include intestinal bacterial overgrowth, reduced xylose meta- bolism in cases of liver disease;, sequestration into ascites, age, and the state of renal function.

4. The test resufts differentiate patients with ex- tensive disease of the upper small intestine from normal subjects, and from patients with steatorrhoea due to pancreatic insufficiency, in most but not all instances. Blood xylose levels combined with ur inary xylose output aids discrimination.

MECHANISM OF ABSORPTION

EARLY W0RKERS'"2' FOUND THAT D-XYLOSE ABSORPTION from the small in tes t ine was much slower than tha t of D-glucose and D-galactose and concluded that the absorpt ive mechanism of the former was by simple di f fus ion. This conclusion was soon chal lenged: Lar- son and his colleagues '~ showed that , in the rat , D- xylose is absorbed 10 t imes fas ter than L-xylose, and F a r r a r et al.'4; observed inh ib i t ion of D-xylose t r ans - port by D-glucose. More recently, Crane ~s~ found tha t a h igh concent ra t ion of D-xylose inhi,bits mucosal-cell uptake of a low concent ra t ion of D-glucose, and others have demonst ra ted fea tures of an active process. These include t r anspor t inh ib i t ion by D-glucose, ex- cessive inh ib i t ion of t r anspo r t by low tempera tures , ex t rus ion by D-glucose of D-xylose aga ins t a concen- t r a t i on g rad ien t ~'~, inh ib i t ion of D-xylose t r anspor t by sodium replacement wi th potassium, by ouabain, dini- trophenol, phlorizin, and a rbu t i n cT" s). D-xylose absorp- t ion may be delJressed in he red i t a ry glucose-galactose malabsorption(°L

Wiseman ' s group "°~ suggested tha t inh ib i t ion of i n t e s t i na l t r a n s f e r by ac t ive ly t r a n s p o r t e d subs t ances migh t be used as a tes t for active t ranspor t , and Duthie and H i n d m a r s h " " la ter found tha t D-xylose fulfi l led this cr i ter ion of active t r a n s p o r t : D- (but not L-) xylose t r ans f e r by hamster small in tes t ine was par t ia l ly inhib i ted by L-his t id ine and L-methionine, an effect not due to inh ib i t ion of water t ranspor t . Convincing proof of active t r anspo r t was obtained in 1969. Us ing Wiseman ' s everted-sac technique "'~, his

TABLE 1

TRANSPORT OF D- AND L-XYLOSE I N VITRO BY SMALL INTESTINE OF DIET-RESTRICTED AND NORMALLY FED

RATS

[Data from the report by Neale and Wiseman n4' with kind ~ermis- sion of authors and publisher.]

Final Sugar-concentration Ratios (Serosal/Mucosal), mean 4- SEM*

Sugar Diet-restricted Normally Fed

D-xylose . . . . . . . . . . . 1.21 4- 0.06 (121 0.76 4- 0.01 (8) L-xylose . . . . . . . . . . . 0.73 ± 0.03 (8) 0.64 4- 0 02 (8)

*No. of experiments in parentheses.

group had shown":" that, in the r a t s tarved of 20% of its in i t i a l body weight, the positive absorpt ion gra- dient for D-glucose and L-his t id ine was subs tan t ia l ly increased. When this exper iment was repeated with D-xylose "'~, the in tes t ine of die t - res t r ic ted rats de- veloped a pronounced positive g rad ien t (Table 1) ; this was not the case with L-xylose (die t - res t r ic ted rat) or D-xylose (normal ly fed ra t ) . Exper iments in another laboratory indicate tha t active xylose t rans- fer may occur only with low concentrat ions, d i f fus ion p redomina t ing when these are high "~'. There is some evidence of an active t r ans fe r process in man, also "').

THE XYLOSE-ABSORPTION TEST

A typical protocol is shown in Table 2. No food should be given for 8 hours before or during the test, to eliminate the possibility of competition for absorp- tion between the poorly absorbed D-xylose and other more rapidly absorbed sugars in the food; also, food may delay gas t r ic emptying.

A 5-gram dose has been advocated by some au- thors '~°', to obviate the nausea and diarrhoea induced by the larger (25-gram) dose; unfor tuna te ly , however, the smaller dose is less d i sc r imina t ing when 5-hour u r ine collections are used c2". What remains to be

TABLE 2

PROTOCOL FOR TESTING D-XYLOSE TOLERANCE

1. Patient fasts overnight. He is ambulant during test~L 2. Patient empties bladder.

Give 25 g D-xylose in 200 ml water (for children: 0.5 g/kg, to maximum of 25 g). Give further 200 ml water 1 and 2 hours later.

3. Estimate blood xylose at 30 min, 1 hour, and 2 hours. 4. Collect urine for 5 hours, and estimate xylose contenttm;

(< 100 ml urine is considered incomplete collection). BUN, also, should be performed, although normal value does not guarantee unimpaired renal excretion of xylose 1°.

142 HINDMARSH

proved, by direct comparison, is whether the xylose con- tent of a 2-hour collection a f t e r a 5-gram dose (se) is as d iscr iminat ing as that of a 5-hour collection af te r 25 grams. There are two theoretical disadvantages of a 5-gram dose: f i rs t , it is likely tha t when there is bac- ter ia l overgrowth of the small intestine, considerable amounts of xylose are consumed - - some authors quote 10 g of a 25-g dose (-'~ - - and that in this circumstance a small dose would be more likely to give erroneous results than a large one. Second, it has been reported ,ea. e,~ tha t 15-20 g of a 25-g dose is absorbed, largely in the f i r s t 100 cm of the small intestine(='~; thus, theoretically, two-thirds of the absorptive surface of the upper small intest ine could be nonfunctioning without producing abnormal results with the 5-g dose.

FACTORS A F F E C T I N G THE TEST

Bacte r ia - - Low xylose excretion has been recorded in patients with intest inal diverticuli ~=), and antibiotic therapy ~ncreased xylose excretion in all of four pa- t ients with s tagnant- loop syndrome '=2). Therefore, care must be taken when in te rp re t ing xylose values from such pat ients . Carbohydra te metabolism. - - Wyngaarden and his colleagues '~'' showed that only about 50% of a 20-g dose of D-xylose infused i.v. could be recovered from the urine over a 48-hour period. This suggests that the remainder was metabolised (13% of the label was recovered as ~4C0~ in the breath when labelled D-xylose was infused), a theory borne out by the f inding ̀ '-a, of high blood xylose levels in cases of liver disease, which decreases the rate of carbohydrate metabolism. Thus, in such cases, blood and urine xylose vahtes may be falsely high. Carbohydra te loss into fluid spaces. - - The u r ina ry xylose output may be low when xylose is sequestered into ascites"-'L

Age and renal function. - - Xylose output declines with age. The reason for this is unknown, but it has been postulated that renal function - - and consequently xylose excretion - - is affected by the ageing process"eL In f rank renal failure, the blood level is elevated and the renal output of xylose is decreased '2"). Other factors. ~ The blood xylose level peaks sooner in pat ients who have rapid gastr ic emptying con- sequent upon gas t r ic surgery ' 'r ' . I t has been repor ted tha t abnormal thyroid function'-'"', a r t e r ia l 0.. desa- tura t ion cae', and cer ta in drugs (3" influence the tes t results , but the mechanisms have not been elucidated.

VALUE OF THE TEST

In thei r studies of large groups of patients, Benson e t al (~'~ and Christiansen et al (3a) found abnormal 5- hour xylose excretion in most of those with small- intest ine disease, a feature that dist inguished them from those with pancreatic insufficiency. Results of the very extensive studies by Beck and his group ('7''~'"' supported this conclusion ~ and emphasized the im- portance of considering blood levels - - and Findlay et a/(ee) arr ived at s imilar conclusions. Sladen and Kumar (~'~ considered the test of limited value; how- ever, none of thei r 36 pat ients with jejunal disease

~ ¢ _

=~ 3o- • x

• g l u t e n - sensitive enteropathy , untreated o ~j tuten - sensitive enteropalhy, treated • c h r o n i c pancreat i t is w i l h steaiorrhoea m advanced l i ve r c i r r h o s i s ,~ intestinal lymphangiectasia wi th stealorrhoea x norma l

0 , , ,

0 ! 2 5 - I(OUR URINARY EXCRETION OF XYLOS[ I q I

Fig. 1 - - S e r u m xylose levels and ur inary xylose excret ion in patient, s w i th and w i thou t d isorders o/ the sn~zl[ in- testicle. - - , normal l imits .

had a normal ll/2-hour blood level phts normal 5-hour ur inary excretion of xylose, and none of their 38 pat ients without GI disorder had the reverse f indings (ll /~-hour blood level < 30 mg/100 mI, plus 5-hour urine output < 4g). In a retrospective (unpublished) study by C. N. Will iams and J. T. Hindmarsh, the f indings (Fig. 1) were s imi la r to those in Sladen and Kumar 's group: none of the pat ients with untreated gluten-sensit ive enteropathy had abnormal xylose values in both the 1-hour serum specimen and the 5- hour urine collection. Correlation with the established diagnosis showed that results fal l ing within the shaded areas on Fig. 1 could be reliably accepted as normal or abnormal ; those outside the shaded areas indicate a need for re-evaluation.

C O N C L U S I O N S

In most cases of steatorrhoea, a combination of the history, physical findings, and roentgenograms usually indicate clearly whether one should proceed to intes- t inal biopsy or pancreatic-function tests (to d i f ferent i - ate between disorders of the upper small intest ine and pancreas) . However, the xylose-tolerance test is a cheap~ painless, and reasonably reliable method on which to base one's choice of these la t ter ra ther un- p leasan t and t ime-consuming tests, and for monitor- ing the response to t r ea tmen t of g luten-sensi t ive enteropathy,

R E F E R E N C E S

1. Cori, C. F. (1925). J. Biol. Chem. 66, 691-715. 2. Verz~r, F. and McDougall, E. J. (1936). Absorptio,~

f r o m the In tes t ine . Longmans, Green, London, New York, and Toronto, p. 122.

3. Larson, H. W., Blatherwick, N. R., Bradshaw, P. J., Ewing, M. E. and Sawyer, S. D. (1940). J. Biol. Chem. 136, 1-7.

4. Farrar , J. T., Small, M. D., :Bullard D. and Ingelfinger, F. J. (1956). Am. J. Physiol . 186, 549-553.

5. Crane, R. K. (1960). Biochim. Biophys . A e t a 45, 477- 482.

6. Salomon, L. L., Allums, J. A. and Smith, D. E. (] 961). Biochem. Biophys . Res . Com~lut~. 4, 12~-126.

XYLOSE ABSORPTION 143

7. Cs~ky, T. Z. and Lassen, U. V. (1964). Biochim. Biophys. Aota 82, 215-217.

8. Alvarado, F. (1966). Biochim. Biophys. Acta 112, 292- 306.

9. Meeuwisse, G. W. and Melin, K. (1969). Acta Paediat. Scand., suppl. 188, 3-18.

1{;'. Hindmarsb, J. T., Kilby, D. and Wiseman, G. (1966). J. Physiol. (Lond.) 186, 166-174.

l l . Duthie, H. L. and Hindmarsh, J. T. (1966). J. Pllysiol. (Lond.) 187, 195-200.

12. Wilson, T. H. and Wiseman, G. (1954). J. Physiol. (Lol~d.) 123, 116-125.

13. Kershaw, T. G., Neame, K. D. and Wiseman, G. (1960). J. Physiol. (Lond.) 152, 182 190.

14. Neale, R. J. and Wiseman, G. (1969). J. Phy:iol. (Lond.) 205, 159-178.

15. Salem, A. A., Cocco, A. E. and Hendrix, T. R. (1965). Am. J. Physiol. 209, 165-168.

]6. Beyreiss, K., Theile, H. and Willgerodt, H. (1968). Get. Med. Mort. 13, 544 548.

17. Roberts, J. G., Beck, I. T., Kallos, J. and Kabn, D. S. (1960). Ca~. Med. Assoc. J. 83, 112-117.

18. Roe, J. H. and Rice, E. W. (1948). J. Biol. Che~l~. 173, 507-512.

19. Kendall, M. J. (1970). Gist 11, 498-501. 20. Sammons, H. G., Morgan, D. B., Frazer, A. C., Mont-

gomery, R. D., Philip, W. M. and Phillips, M. J. (1967). Gut 8, 348-353.

2]. Joske, R. A. and Haagensen, L. J. (1964). J. Clin. Path. 17, 154-155.

22. Goldstein, F., Karacadag, S., Wirts, C. W. and Kow- lessar, O. D. (1970). Gastroenterology 59, 380 386.

23. Beck, I. T., Rona, S. and Callegarini, U. (1962). Am. J. Dig. Dis. 7, 928-935.

24. Fordtran, J. S., Soergel, K. H. and Ingelfinger,-F. J. (1962). N. Engl. J. Med. 267, 274-279.

25. Beck, I. T., Rona, S., McKenna, R. D. and Kahn, D. S. (]962). Am. J. Dig. D/s. 7, 936-948.

26. Wyngaarden, J. B., Segal, S. and Foley, J. B. (19571. J. Clim Invest. 36, 1395-1407.

27. Marin, G. A., Clark, M. L. and Senior, J. R. (1968). Anm Intern. Med. 69, 1155-1162.

2g. Finlay, J. M., Hogarth, J. and Wightman, K. J. R. (1964). Ann. Intern Med. 61, 411-422.

29. Broitman, S. A., Bondy, D. C., Yachnin, I., Hoskins, L. C., Ingbar, S., and Zamcheck, N. (1964). N. Engl. J. Med. 270, 333-337.

3(}. Milledge, J. S. (1972). Brit. Med. J. 3, 557-558. 31. K~ndall, M. J., Nutter, S., and Hawkins, C. F. (1971).

BriL Msd. J. 1, 533-536. 32. Benson, J. A., Jr., Culver, P. J., Ragland, S., J~nes,

C. M., Drummey, G. D. and Bougas, E. (1957). N. E,~gl. J. Med. 2:6, 335-339.

33. Christiansen, P. A., Kirsner, J. B. and Ablaza, .I. (1959). Am. J. Med. 27, 44~3-453.

34. Sladen, G. E. and Kumar, P. J. {1973). Brit. Med..1. :~. 223-226.