Sorbitol as a cryptic cause of diarrhea

Sorbitol is a poorly absorbed monosaccharide widely used as a 
sweetener for dietetic foods and as a drug vehicle. Ingestion of sorbitol can lead to 
gastrointestinal complaints such as cramps and diarrhea. Two patients in whom unrecognized sorbitol ingestion produced symptoms which mimicked an exacerbation of 
another underlying disorder are presented. The diagnosis of sorbitol induced symptoms may be missed or delayed because patients do not appreciate that they are 
ingesting the compound in 'sugarless foods', and drug product information may not 
list its inclusion as a sweetener.

S ORBITOI IS Wll)EI y usrn AS A SWEIT encr for dietetic foods and as ad rug veh icle.It b a monosaccharide which i~ poorly absorbed from the intestine and ingestion can induce an osmotic diarrhea.Gryboski (I) w;is the first to describe the occurrence of this diarrhea in children consuming dietetic candies.Later, Hyams l2) ~tudied the effects o( varying dose~ of sorbitol on healthy adult volunteers and demonstrated that the ingestion of even small amounts can lead to functional complaints such as cramps and bloating without diarrhea.Two cases in which cryptic sorbitol ingestion in hos• pitalized patients induced symptoms that mimicked exacerbation of their underlying medical cond itions arc presented . Division of Pediatric Gastroenrerolog) '  Ou1d revealed no pathogen~ lleostomy fl uid output remai ned elc-1-att'd Analysis of stoma effl uent revealed an osmolarity of282 mOsm/kg.sod ium 59mmoVL, potassium 6.6 mmoVL.chloride 27 mmol/L and an osmolar gap of 151 mOsm/kg.The patient was informed th,;r the symptoms migh t be due to the mg~suon of some agent wh ich induced an osmotic di ar rhea, but she den ied mg,•suon of food, medication or laxamc, A room search failed to reveal any laxativeti.lleostomy fluid a nd urine creen~ for phenolphthalein and senna wm negative.The fo llowing day the pauent and her mother vol u ntee red th e addmonal infor mation that she had for ,ome ume been chewing 14 to 28 sticks of Trident sugarless gum per day.Each su.:kcontains0.93g of sorbicol, 0.40 g of xyhtol and 0.04 g of mannitol; a total of 131 g per stick.Total daily intake of sorbitol alone ranged between 13 an d 26 g representing ingestion of 72 to 145 mOsml of poorly ahsorhablc solute pe r Jav The patient ceased chcll'mg gum and owr the next 24 h there was ;1 cessation ot ahJominal cram rs and a decrcast' in 1 lco,tomy output to less than 450 ml/day A normal diet was resumed, rarcn tera l nutnuon stopped and ileostomy cffluentrcmamcd appropriate in volume and con,1s1ency.There was no osmolar gap on repeat assessmen t

CASE TWO
In June 1987 a six-month-old (cmalc mfant with ryrosincmia was ad mined to ho,p1tal 1111th failure to th n Vl', vomiting .
\ol 2 No 4. November 1988 diarrhea and hepacosplenomegaly.There was bioche mical and rad iological evidence of rickets T he d iagnosis of tyrosincmia was based on urmary and plasma amino acid ch romatograp hy.The patient \\'as placed on nil by mouth and on total parenteral nutrition wtth parenteral calcium supplements because of the rickets.Vomiting and diarrhea resolved and the patient gained weight.
Following clinical and biochemical impm\'ement , a low tyrosine d iet and oral medications were commenced O ral medications consisted of a calcium supplement (Calc1um-Sandm syrup; Anca Pharma, 23 ml qid) providing 506 mg elemental calcium per day, 1-25 d ihy-droxycholccalc1ferol ( Rocaltrol; Roche.125 µg bid), potassium phosphate 500 mg q1d, pyridoxme 2 5 mg daily, vitamin K 2. 5 mg daily, vitamin E 50 iu per Jay and -acerylcysteme 20";, 2 ml every 4 h T he patient developed a recurrence of frequent watery stools, b ut was afebrile, not dehydrated and appeared co be improving clinically.Stool volume ranged fro m 285 to 420 ml/day.Stools were negative for reducing su bstances; stool virology and cu lture fo r bacteria fa iled to reveal the presence of pathogens.Metabolic control of the underlying ryrosinemia deteriorated with wide fl uctuations in scrum tyrosine levels.The milk-free formula fed to the in fa n t contained a mixture oflsomil (Ross Laboratories), 3200-AB (Mead-Johnson} and 80056 (Mead-Johnson ), balanced to provide essential amino acids at appropriate levels.Carbohydrate content was sucrose 7%.Feeds were discontinued and total parenteral nutrition recommenced, however, the loose, watery stools persisted.
E'\amination of prescribing 111forma• Sorb ltol and d iarrhea non ava ilable fo r the oral med1ca1mns made no mention of :-in osmmically active vehicle When ,pecific enquiries were made to the manufacturer it was learned that the sorbitol content of Calcium-Sando: syrup \\'as 0. 354 g/5 ml.The daily do,c of92 ml contamcd 6.5 g of sorhi tol representing an nsmt1t1c load ot' 16 mO,m per Jay The meJicatton was discontmued and replaced with calcium carbonat<.:.Watery d iarrhea ceased wnhin 12 hand feeds ll'erc recommenced 24 h later ll'tthout recurrence of diarrhea

DISCUSSION
Sorb1tol is a hexa hyd ric alcohol with abou t half the sweetness of sucrOSl'.Its systemic toxici ty is vcrv low ( 3.4 ) even by the parenteral route ( 5,6).Small intesti nal absorption of sorbitol is minimal ( 7 l. the majority of the drug reaching the large bowel Fcrmention by enteric bacteria further increases the osmolar load .lnge,tion of as little as 5 g can be detected hy excess breath hyd rogen production ( 2 ).After an oral dose of 10 g, 71 ''o of adult subjects note mi ld gastrointesti nal di stress with gas and bloating (8).A Cter 20 g. 57'';, develop abdominal cramps and diarrhea (H).
The Canad ian Society of Hospita l Pharmacists estimates that 31.5% of oral liquid pharmaceuticals marketed in Canada contain sorbitol (9).ln the two cases described the presence of sorbitol in the diet was not initiall y recognized and a number of investigative procedures were performed before the cause of the sym ptoms was established.In the fi rst case the symptoms induced by sorbitol ingestion mimicked an exacerbation of Crohn's disease.The unintention.ilad ministrauon of snrhitol to the second patient 111 the form of a drug \'Ch icle resulted in d1ar-Le sorbitol, une ca u se c ryptiquc de diarrhee RESUME: Le sorhitol est u nc monosaccharinc diffici le a abwrbcr qui est largement uulist't' commt' succedanc du sucre ct comme vch1cu le de medicament L'ingcst1on du s<1rhirol pt'Ut entrainer des troubles gastrointestmaux relics les crampcs ct ks diarrhccs.Nous prcsentons deux pat ients che:: q u i l'ingesuon non id cntificc de sor• hnol a pmduit de, sympti',mes 1111itant l'exacerbat1t1t1 d'un autre dcsordrt• ,ous•Jact•nt Le diagnostic correct peur ctrc manquc ou retardc parce quc lcs patients nc rcalisL'nt pas qu'ils absorben t k CtimpoM.: da ns les aliments 'sans sucrc'.D\1u 1rc pa r t, lcs re11,c1gnemcnts tourni, avec le, mt'.•dicamems n'inclucnt pas tnuinurs le sorhitol comme succt•dani• du sucre.