Xylitol Poisoning in Dogs: Causes, Symptoms, Treatment, and Prevention

1. Introduction to Xylitol

Xylitol is a sugar substitute frequently used in sugar-free gum, some candies, nasal mints, chewing gum, baked goods, and other products. It is a 5-carbon sugar alcohol that was first discovered in the late 19th century. Xylitol can be found naturally in low concentrations in fruits, vegetables, mushrooms, and sugar cane. Xylitol is a type of artificial sweetener known as a sugar alcohol, which is a chemical compound, termed polyol, that has both alcohol and ketone or aldehyde groups. Because sugar alcohols are similar in structure to sugars, they can stimulate the same taste receptors on the tongue. Sugar alcohols do not contain any carbon to carbon (C–C) bonds, hence they are not fermentable by oral bacteria. Sugar alcohols are employed as food additives because they provide the sweet flavor of sugar with fewer calories and do not promote tooth decay. Elegantly designed studies have been conducted to examine the potential use of sugar alcohols in treating obesity and associated diseases like diabetes and metabolic syndrome (M. Rajapaksha et al., 2019). Although xylitol consumption has been proven to be beneficial to humans, it can be fatal to dogs (Cortinovis & Caloni, 2016).

1.1. What is Xylitol?

The aim of this section is to describe the xylitol commonly found in a dog's food. Xylitol is a sugar alcohol (polyol or sugar substitute) with the chemical composition of C5H12O5 (C5H12O5, CAS No 87-99-0). Xylitol is a 5-carbon sugar alcohol (pentitol) that is a white, crystalline solid at ambient temperature. The molecular weight of xylitol is 152.17 g mol-1 (Cortinovis & Caloni, 2016). Without an odor and with a slightly sweet taste, xylitol can occur naturally in low concentrations in various fruits (such as strawberries, pears, and plums), some vegetables (such as spinach and carrots), and in the bark of birch trees and beech trees, from which xylitol was first isolated (M. Rajapaksha et al., 2019). Xylitol is sold in powdered and crystallized forms like table sugar and is the most commonly used and consumed sugar substitute in a dog's food.

In animals, the primary role of dietary sugar alcohols is to replace sugars and artificial caloric sweeteners in food products as 'non-cariogenic' alternatives. Sugar alcohols, once ingested, do not cause any fermentation in the mouth. For example, xylitol is extensively used in sugar-free chewing gums since these products have become very much in vogue among health-conscious consumers. The consumption of sugar-free gum can help reduce the incidence of caries, and it is perceived that chewing gum can be an effective means for weight loss. While sugar-free food products substitute calorically higher sugar by non-cariogenic sugar alcohols, such as xylitol, the health benefits of reducing sugar in food can be countered by greatly increasing the intake of calorically lower sugar alcohols.

1.2. Common Sources of Xylitol

Many household food items can be toxic to dogs and cats. These include chocolate, onions, garlic, grapes, raisins, macadamia nuts, raw bread dough, caffeine, alcohol, and tobacco. Some human medications can cause serious toxicity in pets, including acetaminophen (Tylenol), ibuprofen (Advil, Motrin), antidepressants (Prozac, Effexor), alcohols (ethanol, isopropyl), and iron tablets (Cortinovis & Caloni, 2016).

One of the newest and most dangerous hazards to dogs is xylitol, a sugar replacement commonly found in sugarless gum, breath mints, toothpaste, and other sugar-free food items. Xylitol is extremely toxic to dogs but has no ill effects on humans or cats (M. Rajapaksha et al., 2019). Many newer brands of chewing gum contain xylitol as an ingredient, including fruit-flavored gums. Even a small amount can be lethal to a dog. Because it has been a common ingredient of diet food items for years, not a lot of people know that it is dangerous. Hence it is very important for dog owners to be aware of it.

2. Xylitol Toxicity in Dogs

While dogs and other pets can still get into trouble, it becomes more challenging when humans are unaware of which items are dangerous. Many household items that one would consider safe can have serious consequences. In recent years, xylitol, an artificial sweetener, has become increasingly common in products like chewing gum and sweetened water. Unfortunately, xylitol is also toxic and potentially deadly to dogs (Cortinovis & Caloni, 2016).

The sweetener xylitol has become more common over the past decade in products such as chewing gum, breath mints, and sugar-free candies. Most people do not even know what xylitol is and think it is a safe sugar substitute. However, xylitol is extremely dangerous and potentially lethal to dogs, even in small amounts. Dogs are unique in their extreme susceptibility to xylitol toxicity; they rapidly absorb the sweetener and experience a massive release of insulin from the pancreas. Insulin secretion lowers the dog’s blood sugar (glucose) levels, leading to hypoglycemia or low blood sugar. The clinical signs of hypoglycemia, which can occur in as little as 10 minutes after ingestion, include weakness, stumbling, ataxia, lethargy, vomiting, and, if untreated, seizures, coma, and eventually death.

2.1. Mechanism of Xylitol Toxicity

As other sugar alcohols, such as sorbitol and mannitol, xylitol is an organic compound and a methylpentane polyol. Unlike glucose, xylitol is actually taken up by the liver rather than the pancreas, bile or kidneys (Cortinovis & Caloni, 2016). More importantly, enteral xylitol causes a rapid increase in insulin release and anti-diabetic hormones, which results in hypoglycemia within 30 minutes of intravenous or oral administration of xylitol. Importantly, the liver uptake of xylitol activates several limiting enzymes, including xylitol dehydrogenase and xylulose kinase, subsequently resulting in the conversion of xylitol to xylulose, which is further phosphorylated to xylulose-5-phosphate (XP). Accumulation of XP stimulates regulatory pathways of lipogenesis, and induces tubule swelling, constrictive perihepatocellular fibers, and failure of intercellular communication. Furthermore, continuing cell death and disruption of insulin receptors would enhance blood glucose decrease and aggravate hypoglycemia in dogs. Along the same line, decreased hepatic glycogen and ATP would impair other liver functions, such as albumin synthesis, detoxification of ammonia and thrombocytes, leading to hepatic encephalopathy, plasma ammonia accumulation, and blood hypercoagulability. Xylitol-induced hepatotoxicity and hepatic failure is thought to be largely different from other hepatotoxicants, such as acetaminophen and phosphorized insecticide.

2.2. Symptoms of Xylitol Poisoning

The clinical manifestations of xylitol poisoning generally begin 30-60 minutes after the consumption of xylitol (Cortinovis & Caloni, 2016). Symptoms may include lack of energy, weaknessful behavior, disorientation, stupor, collapse, seizures, and vomiting. Symptoms of xylitol toxicity can be so severe and escalate so quickly that the dog can die from xylitol poisoning, even prior to being taken to a veterinarian for care. After the ingestion of higher quantities of xylitol, acute hepatic necrosis may occur in dogs, leading to possible subsequent liver failure.

Eating xylitol on a regular basis over time can prepare a dog’s body to secrete ample amounts of insulin when a steward (its owner) diligently feeds the drug to it. Unfortunately, consuming xylitol in a shorter than normal time period can trigger a rush of insulin secretion. After ingestion of other popular sugar substitutes, such as sorbitol and aspartame, xylitol is absorbed extremely fast into a dog’s bloodstream. Blood glucose levels in dogs may drastically drop to almost nonexistent levels if treatment is not promptly initiated.

3. Diagnosis and Treatment

If you observe your dog exhibiting symptoms of xylitol toxicity, it is imperative to seek immediate veterinary attention. It is important to provide your veterinarian with specific information, including how much xylitol your dog ingested, the time of ingestion, and the weight of your dog. If your dog is conscious and showing no symptoms of poisoning, your veterinarian may recommend inducing vomiting. However, this is only advised if your dog has ingested xylitol within the past 30 minutes. Once at the veterinary clinic, a complete physical exam will be performed, and blood tests may be conducted to evaluate glucose and liver enzyme levels. When liver enzymes are elevated, additional tests are often performed. These tests may involve an ultrasound to evaluate liver blood flow and look for masses, shunts, or other pathologies (Cortinovis & Caloni, 2016). A liver biopsy may also be necessary, with microscopic evaluation of liver cells, although this procedure is more invasive and may require hospitalization.

Unfortunately, if a dog experiences liver failure, the prognosis is poor, and treating liver failure can be complicated and expensive. Acute hepatic failure associated with xylitol ingestion has been reported in otherwise healthy dogs. If symptoms of poisoning are present, be prepared to leave your dog at the veterinary hospital. Symptomatic treatment is likely to begin, which may include hospitalization and intravenous fluids, glucose supplementation, blood pressure support, anti-nausea medications, and medications to diminish liver toxicity and restore proper blood flow. Symptoms of hypoglycemia (abnormal liver enzymes and low glucose levels) usually resolve within 24 hours. However, abnormalities in liver function (elevated liver enzymes) may persist for several days. Dogs with abnormal liver function must be closely monitored to prevent further damage.

3.1. Diagnosis of Xylitol Poisoning

Diagnosis will be based on clinical signs and history of exposure to xylitol-containing products. In addition, laboratory findings showing hypoglycemia (blood glucose value <60mg/dL) and other changes (prolonged prothrombin time, increases in alanine aminotransferase, aspartate aminotransferase, and total bilirubin concentration) will be considered suggestive of xylitol exposure. A definitive diagnosis will be based on identification of xylitol from the stomach contents, vomitus, or the xylitol-containing product (gum, candy, mints, etc.) by gas chromatography-mass spectrometry (GC-MS) (M. Rajapaksha et al., 2019).

However, results might not be immediately available, thus treatment will begin as soon as exposure is confirmed and clinical signs are observed. In case of ingestion of xylitol-containing products, monitoring for hypoglycemia every 2h for 18h is suggested in dogs, even in those dogs who were not treated, as hypoglycemia was documented in dogs 8h after gum ingestion. Monitoring of liver enzymes and prothrombin time is suggested in suspected cases of xylitol ingestion, even if initial values were normal.

3.2. Treatment Options

If ingestion of xylitol is witnessed, or suspected, and after contacting a veterinarian, dogs should be taken for evaluation. Typical clinical management varies by the size of the dog and the amount of xylitol consumed. Routine management of xylitol ingestion in dogs can involve inducing vomiting and administering activated charcoal, which absorbs toxins and prevents their absorption (Cortinovis & Caloni, 2016). Anticipated complications due to toxicity include hypoglycemia, liver failure, thyroid dysfunction and so on.

If needed, dogs can also receive intravenous fluids with an electrolyte solution to stabilize blood sugar, monitor liver function, receive medications to encourage urination or protect the liver, vitamin K1 to improve blood clotting, and/or other treatment options (Cortinovis & Caloni, 2016). Closely monitoring liver enzymes is critical to determining if more aggressive therapy is required. In rare, severe cases of toxicity, dogs may need surgical intervention to remove a large xylitol-related object, or treatment with antioxidants, bile acids, or transfusions.

4. Preventing Xylitol Poisoning

The best way to treat xylitol poisoning is to prevent it from occurring in the first place. As a dog owner, it is important to be aware of what food items may be toxic to dogs and ensure that those items are not kept where they are easily accessible. Avoid foods that contain xylitol or any other items that may be toxic to dogs (Cortinovis & Caloni, 2016). If you must have it in your house, make sure that it is in a place where your dogs cannot reach it. Always keep these kinds of products in a secured cupboard and remember to check the labels before offering your dog anything new. There are many dog-safe alternatives to human food products that can be used as a treat instead. Look for dog-safe peanut butter, cheese, or yogurt instead of products that contain xylitol or other potentially harmful substances.

4.1. Tips for Preventing Xylitol Poisoning

Be Aware of Products Containing Xylitol Whether or not your dog has consumed a xylitol product, you can take steps to limit your dog’s exposure. What foods and items contain xylitol? Most commonly used as a sugar substitute in sugar-free chewing gums, xylitol is also used in other food products, including baked goods, gummies, mints, candy, liquids, sauces, chocolate, and even peanut butter. However, not all brands of products containing these ingredients use xylitol. For example, Skippy peanut butter does not contain xylitol, but a brand like Go Nuts Co. does contain xylitol (Cortinovis & Caloni, 2016). Additionally, xylitol is an ingredient in sugar-free dental products, specifically chewing gum and toothpaste. It can even be found in toothpastes designed for dogs! As newer products appear on the market, it is best to check any new products you have not had before. Contact the manufacturer by calling or checking their website for a product’s ingredients, or look for the ingredient on the product label when shopping.

Keep Xylitol Containing Products Out of Reach It is important to keep all products that could potentially contain xylitol out of your dog’s reach, especially food or dental products. This may involve storing these items in cabinets with childproof latches or locking cabinets. Do not leave products on countertops, tables, or anywhere within the bounds of a curious dog. If there is a spill, immediately clean up all remnants. Rinse any xylitol residue on the floor, as just licking some gum wrapper residue caused one dog to be severely affected.

4.2. Alternative Sweeteners for Dogs

Erythritol is a natural sugar alcohol that is 60-70% as sweet as sugar. Unlike xylitol, ingestion in dogs is not toxic, leading to a widespread search for xylitol alternatives in dog products. However, not all sweeteners are safe for canine consumption. A notable ingredient, "Stevia extract," is often used in "natural" or "herbal" products. While it does not appear to be toxic, its safety has not been fully tested in dogs.

Carob, a legume native to the Mediterranean region, is safe for dogs. Its powder is a common substitute for chocolate in dog treats. Carob is low in fat, contains no theobromine, and is naturally sweet, making it palatable for dogs. Carob is rich in fiber, antioxidants, and flavonoids, benefitting dogs with diabetes or cancer. Natural honey and molasses products have traditionally been used in dog treats, but they contain high sugar levels and do not support canine health.

Algalodextrin and other fiber additives like chicory root (inulin) are becoming more common as prebiotic fiber sources with claimed health benefits. However, there are generally no health benefits to adding fiber to dog foods or treats. Artificial sweeteners are unnecessary in dog foods and treats but commonly used in reduced-calorie, low-sugar products. Saccharin (Sweet'n Low) is not toxic to dogs (Cortinovis & Caloni, 2016) but is not considered palatable. Aspartame (NutraSweet) is not toxic but does not effectively sweeten most dog foods. Sucralose (Splenda) is not toxic to dogs but may not be palatable in high-sugar foods.

5. Conclusion and Future Research

In summary, this review describes the causes, symptoms, treatment, and prevention of xylitol poisoning in dogs. Xylitol is an artificial sweetener increasingly used in over-the-counter and prescription products. Its toxicity to dogs was documented in CellMet in 2008. Accidental ingestion of certain products in dogs induces rapid release of insulin from pancreatic beta-betal cells, resulting in hypoglycemia. Further studies are needed to fully understand the mechanism of xylitol poisoning and to develop improved treatments. Increased public awareness of product labeling can prevent dog exposure. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest (Cortinovis & Caloni, 2016).

References:

M. Rajapaksha, S., Gerken, K., Archer, T., Lathan, P., S. Liyanage, A., Mlsna, D., & E. Mlsna, T., 2019. Extraction and Analysis of Xylitol in Sugar-Free Gum Samples by GC-MS with Direct Aqueous Injection. ncbi.nlm.nih.gov

Cortinovis, C. & Caloni, F., 2016. Household Food items Toxic to Dogs and Cats. [PDF]

Cortinovis, C. & Caloni, F., 2016. Household Food Items Toxic to Dogs and Cats. ncbi.nlm.nih.gov