The first adverse effect discovered
During the 1960s, researchers trying to determine the feasibility of using xylitol as an energy source in parenteral nutrition
made an unexpected discovery. In dogs, intravenous xylitol caused a dose-related release of insulin, greater than the amount
released in response to an equal dose of glucose, which could result in a concurrent drop in blood glucose concentrations.10,11 Insulin release is also seen with oral dosing of xylitol. In one study in dogs, peak serum insulin concentrations after
ingestion of 1 g/kg of xylitol were six times greater than those after ingestion of 1 g/kg of glucose. While serum glucose
concentrations rose after ingestion of glucose, the glucose concentrations in the dogs given xylitol orally dropped rapidly
and reached a low of about 50 mg/dl one hour after administration.6 Cases reported to the ASPCA Animal Poison Control Center (APCC) indicate that dogs ingesting > 0.1 g/kg could develop hypoglycemia.12
After xylitol ingestion, vomiting is usually the initial sign. Hypoglycemia may develop within 30 to 60 minutes.13 However, in some cases of xylitol gum ingestion, hypoglycemia may be delayed for up to 12 hours (ASPCA APCC Database: Unpublished
data, 2003-2006). The clinical signs may progress rapidly from lethargy to ataxia, collapse, and seizure.12 Initial blood work most often shows profound hypoglycemia12 ; in some cases, though, the dogs have presented with hyperglycemia (ASPCA APCC Database: Unpublished data, 2003-2006). The
latter finding may be similar to the Somogyi phenomenon that is seen in cases of iatrogenic insulin overdose.14 Other common serum chemistry abnormalities include hypokalemia, due to insulin's property of moving potassium into the cell
along with glucose,15 and hypophosphatemia, since insulin can increase cellular permeability to the phosphate ion.16
Xylitol's effect on blood glucose varies greatly among species. In people, rats, horses, and rhesus monkeys, intravenous xylitol
causes little to no increase in insulin release or changes in blood glucose concentrations.17 On the other hand, intravenous xylitol can cause large insulin release in cows, goats, rabbits, and baboons.17,18 Xylitol's effect on insulin release and blood glucose in cats and ferrets is unknown.
Warning to owners: Do not give these sweets to your dogs
A newly discovered danger
Recently, the ASPCA APCC has had reports of some dogs developing elevated liver enzyme activity within 12 to 24 hours after
xylitol ingestion.12 Several of these dogs developed acute liver failure subsequent to xylitol exposure.12 In a case report on liver failure following xylitol ingestion in eight dogs (see "Warning to owners: Don't give these sweets to your dogs"), six of the eight dogs did not appear to develop hypoglycemia before the onset of the liver failure.12 Instead, lethargy and vomiting developed nine to 72 hours after exposure. Coagulopathy, characterized by prolonged clotting
times and petechial, ecchymotic, and gastrointestinal hemorrhages, was also present in the dogs.
Clinicopathologic findings present in all the dogs included elevated alanine transaminase activity (often well beyond the
analyzer's range), mild to moderate hyperbilirubinemia, and severely prolonged coagulation times (prothrombin time, activated
partial thromboplastin time, or both). Other common findings included mild to moderate thrombocytopenia, mild elevation of
alkaline phosphatase activity, moderate hypoglycemia (a finding attributed to liver failure rather than xylitol's direct effect
on insulin release), and mild to moderate hyperphosphatemia. Hyperphosphatemia was a poor prognostic indicator.
Five of the eight dogs were either euthanized or died. Three dogs were necropsied; two had severe hepatic necrosis, while
the third had generalized loss of liver cells with collapse of the liver's architecture.12 The lowest estimated dose associated with liver failure to date has been 0.5 g/kg (ASPCA APCC Database: Unpublished data,
2003-2006); however, it is not clear at this time whether the effect is dose-related or idiosyncratic.