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Xylitol Toxicity

Xylitol Toxicity: Not Just Gum
Linda Barton, DVM, DACVECC

The number of dogs presenting for xylitol ingestion and toxicity has increased dramatically over the past few years. Xylitol is a crystalline sugar alcohol used as a sugar substitute sweetener in many products including sugar-free gum, candy, chewable vitamins, nutritional supplements and baked goods. It is available in a granulated form for baking. Based on demonstration of anti-cariogenic properties, xylitol is added to toothpastes and other oral hygiene products. In a retrospective evaluation of 192 cases of xylitol ingestion, 96% of the dogs presented for ingestion of sugar-free gum.xy1

Xylitol has a wide margin of safety in people but is extremely toxic to dogs. Compared to humans, dogs experience a rapid and severe increase in blood insulin resulting in profound hypoglycemia which can last up to 24 hours. Similar effects are seen in cows, goats and rabbits. Cats and ferrets have not shown toxic effects. Ingestion of large amounts of xylitol has resulted in liver failure in dogs.

Diagnosis of xylitol toxicity is based on history of ingestion, symptoms and bloodwork. Common presenting clinical signs include vomiting, lethargy and weakness. Diarrhea, collapse and seizures may be seen. Hypoglycemia has been reported within 30 minutes of ingestion but can occur up to 12 hours post-ingestion.

Treatment recommendations are based on the amount of xylitol ingested (see table below). There is no known antidote and a narrow window for safe decontamination. Xylitol is rapidly absorbed with peak plasma concentrations at 30 minutes. Emesis is recommended in asymptomatic dogs. Activated charcoal is not likely to be beneficial as charcoal does not bind to alcohol-type compounds.

Calculating the amount of xylitol contained in products can be difficult. Products that list xylitol as the first ingredient tend to be the most toxic. The amount of xylitol in gum can range from 0.9 mg to 1000 mg/piece. While some gum products specify the xylitol content on the label, many manufactures consider this to be proprietary information. The ASPCA Animal Poison Control Center (ASPCA APCC) recommends that if xylitol is the first sugar alcohol in the ingredient list, then the estimated dose should be based on the total amount of sugar alcohols. If not the first ingredient, xylitol should be estimated to be 0.3gram/piece of gum. Granulated (baking) xylitol contains 190 grams/cup. Gabapentin liquid contains 300 mg xylitol/ml and could reach toxic levels at higher doses.

The ASPCA APCC recommends that dogs ingestixy2ng 50-100 mg/kg should receive decontamination and monitoring. However, hypoglycemia has been reported in a dog ingesting an estimated 30 mg/kg xylitol dose. Dogs ingesting >100 mg/kg are at increased risk for hypoglycemia and should be treated more aggressively. Ingestion of higher doses increases the risk of liver failure and coagulopathy. All dogs reported developing xylitol induced liver failure ingested > 500 mg/kg; however, it is not clear at this time whether the effect is dose-related or idiosyncratic. In a case report of dogs developing acute liver failure subsequent to large dose xylitol exposure, six of the eight dogs did not develop hypoglycemia prior to the onset of liver failure.

The prognosis is very good for dogs treated promptly and for dogs with uncomplicated hypoglycemia. In a 2015 retrospective study reporting 192 cases of xylitol ingestion, 15.6% developed hypoglycemia and 21.9% of dogs with serum biochemistry panels performed developed mildly increased ALT or total bilirubin. No dogs developed clinical signs or biochemistry values consistent with liver failure. All dogs survived. Mild increases in liver enzymes usually resolve within a few days with supportive care.

Severe or progressive increases in liver enzyme activities (>1000),xy3 hyperbilirubinemia and coagulopathy, carry a more guarded prognosis. Mortality rate of 70-80 is reported when acute liver failure develops. Hyperphosphatemia appears to be a poor prognostic indicator. At BluePearl, we have treated several dogs with severe liver failure and coagulopathy secondary to xylitol ingestion. Although we have not been able to save all of them, we have gotten a good number home after treatment with fresh frozen plasma, fluids, GI protectants and liver protectants. In one case in which the dog ate two cups of baking xylitol, the dog developed active bleeding due to coagulopathy and ALT went up to 50,000. However, after several plasma transfusions, the dog was able to go home and bloodwork was completely normal 8 weeks later.

Ingested DoseTreatment recommendation
 50-100 mg/kgInduce vomiting if asymptomatic, observe
100-500 mg/kgInduce vomiting if asymptomatic. Obtain baseline glucose, potassium, phosphorus, biliruibin and liver enzymes. Monitor blood glucose every 1-2 hours for at least 12 hours and other tests every 24 hours for at least 72 hours. If hypoglycemia develops, 1-2 ml/kg bolus of 25% dextrose and continue fluids supplemented with 2.5-5% dextrose to maintain normal glucose. Continue until glucose concentration can be maintained without supplemental dextrose.
>500 mg/kgAs above, except administer supplemental dextrose despite normal BG.  Add liver protectants (N-acetylcysteine or Denamarin)