Ylva Sjöström 1) and Anna Lennquist 2)

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1 Ylva Sjöström 1) and Anna Lennquist 2) 1) VMD, Swedish specialist in diseases of dogs and cats, Blue Star Animal Hospital, Gjutjärnsgatan 4, SE Gothenburg, Sweden 2) PhD in Zoophysiology, Dept. of Zoology, University of Gothenburg, Box 463, SE Gothenburg, Sweden Xylitol, grapes and raisins can be fatal for your dog Something about the effects of these substances on dogs Be careful where you put fruit and sweets if you have a dog at home! Grapes, raisins and products containing xylitol can cause life-threatening damage in dogs. The number of poisonings and subsequent deaths has increased over the past years, and it is still unclear why things that are sweet for us are toxic for dogs. Figure 1. Xylitol is used as a sweetener in many products today, due to its anticavity effects. Photo: Ylva Sjöström. CORRESPONDENCE TO Ylva Sjöström ylva.sjostrom@blastjarnan.se More and more cases reported Animal Poison Control Center (APCC), a 24 hour service centre in the US, receives calls from veterinarians and animal owners who suspect poisoning. The first calls regarding dogs that had eaten xylitol products were received in 2002, and in 2004 the first case study of a xylitol-poisoned dog was published. In February of 2008, the Veterinary Poisons Information Service in London released a request to veterinarians in Britain to be observant of xylitol poisoning, since the number of cases was increasing. Also at the Swedish Poison Control Centre the number of calls regarding xylitol and dogs appears to be increasing. Xylitol is a sugar with sweetness similar to that of ordinary glucose although with a 40% lower calorie content. Since the start of manufacturing in the 1970 s it has become an increasingly popular sweetener. In addition, xylitol has an anti-bacterial effect, and thus an anti-cariogenic effect, making it useful in, for instance, children s toothpaste. Today xylitol can be found in desserts, ice cream, sweets, jam, chewing gum, sauces and breakfast cereals. Even medicines, such as fluoride tablets, vitamins and nicotine chewing gum may contain xylitol. Lately, xylitol is being used to sweeten bread in the US and in Britain. (Fig. 1).

2 Figure 2. Both grapes and raisins can cause poisoning in dogs. Photo: Ylva Sjöström. Grapes and raisins are not new foods, but also in this case there appears to be an increase in the number of poisonings. Perhaps this is simply due to the fact that the problem has attracted more attention. In 1994, the Veterinary Poisons Information Service received the first report of a dog that had shown symptoms of poisoning after having eaten raisins, but not until 2001 was the first article regarding this observation published. Since then, the number of reported cases has increased both in the US and in Britain, and also the Poison Control Centre in Sweden receives an increasing number of calls regarding this. Grapes may be white/green or red/blue, and raisins are dried grapes. There are three different colours of raisins, where the dark ones are sundried, the brown mechanically dried and the golden ones are mechanically dried and then bleached using sulphur dioxide. Attempts have been made to find connections between poisoning and colour, origin or pesticide spraying of the grapes, but no such relationship has been found. However, most poisonings involving raisins seem to occur with sundried raisins from various commercial dealers. (Fig. 2). Xylitol drastically lowers blood sugar levels and damages the liver in dogs The most common clinical symptom in a xylitolpoisoned dog is vomiting, often within an hour. Other symptoms are lethargy, impaired muscle coordination, seizures and collapse. If xylitol poisoning is suspected, a veterinarian should be contacted immediately. In a dog, xylitol is very rapidly absorbed in the stomach to be subsequently metabolised by the liver. Xylitol triggers a massive release of insulin from the pancreas, and this in turn causes a major fall in blood sugar level hypoglycaemia. Some of the symptoms of xylitolpoisoning can be explained by the hypoglycaemia. A more serious problem is that xylitol in addition may cause acute liver failure (necrosis). There are two hypotheses for the mechanism behind this. The first hypothesis is that the liver exhausts the stores of ATP (adenosine triphosphate) during the metabolism of xylitol, and therefore lacks the necessary ATP levels to maintain normal cell functions. The second hypothesis rests on the large quantities of free oxygen radicals (please see the article on antioxidants in this issue of Bioscience Explained) formed dur- 2

3 ing metabolism of glucose, and that these free radicals damage the tissue. Initial blood work most often show profound hypoglycemia, as well as low potassium (hypokalemia) and low phosphates (hypophosphatemia) as a result of the insulin release. High blood levels of bilirubin, a by-product from red blood cells, are also common during xylitolpoisoning. This is likely caused by the red blood cells bursting due to glucose shortage. During liver necrosis it is possible to measure increased levels of phosphate ions that are moderate to mildly elevated, and the liver enzymes, AST (aspartateaminotransferase), and ALT (alanine-aminotransferase) are often profoundly elevated. At the veterinarian, the xylitol-poisoning is treated by inducing vomiting, giving activated charcoal orally and giving glucose infusions intravenously sometimes with an addition of potassium. Transfusion with plasma or whole blood and treatment with vitamin K may also be needed during liver failure, as well as treatment with liver protectants and antioxidants. Dogs that have been affected by uncomplicated hypoglycaemia recover well after prompt treatment. If severe liver failure occurs, however, the mortality may be as high as 80%. For a ten kilo dog, as little as two or three pieces of chewing gum may cause xylitolpoisoning. Grapes and raisins may cause kidney failure in a dog Also where poisoning by grapes and raisins is concerned, vomiting is the first symptom followed by increased thirst, lethargy and impaired muscle coordination (ataxia). Some dogs also show reduced urine production. Grapes and raisins may in fact cause acute kidney failure in dogs, but the mechanism behind this remains unclear. It is not known why different individual dogs show such a varied sensitivity to this. There are some theories about the cause of the toxicity. Raisins and grapes left behind after poisoning have been screened for traces of fungicides, herbicides, pesticides, mycotoxins, heavy metals and vitamin D, but no connections or explanations have been found. There have also been discussions on whether the high sugar content could cause a shock, but this explanation does not seem to be sufficient. Another theory is that some individuals may possess special enzymatic systems within their kidney cells, responsible for metabolising some compound in the grapes to a more toxic substance. However, this idea has not been further investigated. 3

4 During poisoning by grapes or raisins, profoundly elevated levels of creatinine and urea are found in the blood. This is due to the reduced ability of the kidneys to excrete these metabolites, which leads to the higher blood levels. High levels of phosphate and calcium are also common. In the urine there may occur glucose, proteins and blood. At the veterinarian, poisoning caused by grapes and raisins is treated by inducing vomiting. Sometimes activated charcoal is also given orally. At kidney failure, fluid therapy is essential. Tube-feeding may also be necessary since the treatment often takes a long time. Acute kidney failure may require several weeks of treatment, and mortality is high, about 50%. As little as four grapes in an eight-kilo dog or a small package of raisins in a dog of 15 kilos may cause poisoning. Figure 3. The risk of poisoning in dogs increases with more xylitol products aimed at children. Photo: Ylva Sjöström. Treats for us but poison for dogs It could easily happen that a dog finds xylitol products, grapes or raisins. It is not hard to imagine that the risk is higher in a home with children, since many xylitol products target children, and since children often leave things where they are easily reachable by dogs. (Fig. 3). How can it be that humans and dogs react so differently towards these foods? Regarding xylitol it is known that the uptake in the stomach is faster in dogs than in humans. Also, in humans there is no stimulation of insulin release by xylitol or a drop in blood sugar levels. When it comes to liver necrosis, the mechanisms behind this are not known in dogs, and thus no comparisons with humans can be made. The same is true for kidney failure caused by poisoning by grapes and raisins. Hopefully, in the near future scientists will identify some of the mechanisms behind the poisonings. Still many people are unaware that xylitol, grapes and raisins may be fatal to dogs. This is also true for veterinarians. When more people become aware of the risks, further poisonings can hopefully be avoided. 4

5 Fact box 1 Toxic quantities of xylitol An ordinary piece of chewing gum weighs 1.4 gram. Most xylitol chewing gums contain 31-33% xylitol, corresponding to gram xylitol/chewing gum. 2-3 pieces of xylitol chewing gum is enough to poison a 10 kilo dog. For other products, e.g., tablets with a xylitol core, the content of xylitol is somewhat lower, about 0.35 g/tablet. But also in this case, 3 xylitol tablets are enough to poison a 10 kilo dog. For xylitol powder or home-baked products with xylitol, it can be estimated that 2.5 dl xylitol powder weighs about 200 gram. Fact box 2 Toxic amounts of grapes and raisins There are many reports of different doses causing kidney toxicity in dogs. The lowest dose reported was 4-5 grapes in a dog of 8.2 kilos and 2.4 grams raisins/kilo body weight in another dog, respectively. A small pack of raisins contains 42.5 gram which would correspond to a toxic dose for a dog of 15 kilos. However, a relationship between ingested amount and poisoning in dogs, has not been found. Fact box 3 Symptoms and treatment at home at xylitol poisoning Symptoms: Vomiting, lethargy Blood sugar decline with impaired muscle coordination and seizures Treatment: Give sugar and call a veterinarian Fact box 4 Symptoms and treatment at home at poisoning by grapes or raisins Symptoms: Vomiting, diarrhoea, increased thirst, lethargy Treatment: Give activated charcoal if available at home. Call a veterinarian 5