Xylitol

Xylitol is a chemical compound with the formula , or HO(CH2)(CHOH)3(CH2)OH; specifically, one particular stereoisomer with that structural formula. It is a colorless or white crystalline solid that is soluble in water. It can be classified as a polyalcohol and a sugar alcohol, specifically an alditol. The name derives from , "xyl[on]", "wood", with the suffix "-itol" used to denote sugar alcohols.
Xylitol is used as a food additive and sugar substitute. Its European Union code number is E967. Replacing sugar with xylitol in food products may promote better dental health, but evidence is lacking on whether xylitol itself prevents cavities.
Structure, production, commerce.
Xylitol is naturally occurring in small amounts in plums, strawberries, cauliflower, and pumpkin; humans and animals make trace amounts during metabolism of carbohydrates. Unlike most sugar alcohols, xylitol is achiral. Most other isomers of pentane-1,2,3,4,5-pentol are chiral, but xylitol has a plane of symmetry.
Industrial production starts with lignocellulosic biomass from which xylan is extracted; raw biomass materials include hardwoods, softwoods, and agricultural waste from processing maize, wheat, or rice. The xylan polymers can be hydrolyzed into xylose, which is catalytically hydrogenated into xylitol. The conversion changes the sugar (xylose, an aldehyde) into the primary alcohol, xylitol. Impurities are then removed. The processing is often done using standard industrial methods; industrial fermentation involving bacteria, fungi, or yeast, especially "Candida tropicalis", are common, but are not as efficient.
According to the US Department of Energy, xylitol production by fermentation from discarded biomass is one of the most valuable renewable chemicals for commerce, forecast to be a US$1.4 billion industry by 2025.
Uses.
Xylitol is used as a sugar substitute in such manufactured products as drugs, dietary supplements, confections, toothpaste, and chewing gum, but is not a common household sweetener. Xylitol has negligible effects on blood sugar because it is metabolized independently of insulin. Absorbed more slowly than sugar, xylitol supplies 40% fewer calories than table sugar. It is approved as a food additive in the United States. Xylitol is also found as an additive to saline solution for nasal irrigation and has been found to be effective in improving symptoms of chronic rhinosinusitis.
Food properties.
Xylitol has about the same sweetness as sucrose, but more sweetness than similar compounds like sorbitol and mannitol. Xylitol is stable enough to be used in baking. Because xylitol and other polyols are heat stable, they do not caramelise as sugars do, and they also lower the freezing point of mixtures in which they are used.
No serious health risk exists in most humans for normal levels of consumption; The European Food Safety Authority has not set a limit on daily intake of xylitol. Due to the adverse laxative effect that all polyols have on the digestive system in high doses, xylitol is banned from soft drinks in the EU. Similarly due to a 1985 report, by the EU Scientific Committee on Food, stating that "ingesting 50 g a day of xylitol can cause diarrhea", tabletop sweeteners containing xylitol are required to display the warning: "excessive consumption may induce laxative effects". Chewing gum containing xylitol is permitted.
Health effects.
Dental care.
Research has identified carbohydrates, oral bacteria, tooth anatomy, along with their time of interaction as the main pathobiological etiology for dental caries. Sucrose is deemed to be the most cariogenic carbohydrate consumed by humans, as it is a substrate to various oral bacteria to produce insoluble polysaccharides and acid. Streptococcus mutans is a major pathological bacteria which utilizes carbohydrates via glycolysis to adhere to tooth surfaces via extracellular matrix and produce an acidic environment, thereby dissolving the outer enamel layer of teeth.
Xylitol, a sugar alcohol containing 5 carbon-polyol is metabolized via the phospho-enolpyruvate-phospho-transferase pathway (PEP-PTS) in S. mutans, which produces xylitol-5-phosphate as a product. Xylitol-5-phosphate competes with phosphofructokinase and therefore, results in inhibition of glycolysis via accumulation of glucose-6-phosphate. Over long periods of time of xylitol use, S. mutans are observed to alter their enzymatic activity.
Burt (2006) conducted a systematic review looking at the effect of sugar alcohols on caries activity. His systematic review included randomized controlled trials (RCT) as well as observational studies. Burt  concluded that Xylitol displayed non-cariogenic properties in all protocols tested. Interestingly, he also concluded that mothers chewing xylitol-containing gums effectively inhibited the transmission of S. mutans to their offsprings. Nayak et al. (2014) also conducted a review where they showed the positive effects of Xylitol in gummy bears, syrups, mouthrinse, dentifrice on inhibiting dental caries. Lastly, Chan et al. (2020) concluded that xylitol has inhibitory effects on S. mutans and C. albicans. However, it is important to mention that the nature of all scientific studies bears some limitations. Other studies including Muhlemann et al. (1977) seem to call for more research in this area as the results were inconclusive. A cochrane review conducted in 2015 included 10 studies which displayed a low quality evidence on the effectiveness of xylitol containing fluoride toothpastes when compared to fluoride only toothpaste.
Ear aches.
In 2011, EFSA "concluded that there was not enough evidence to support" the claim that xylitol-sweetened gum could prevent middle-ear infections with a fast onset, which is also known as acute otitis media (AOM). A 2016 review indicated that xylitol in chewing gum or a syrup may have a moderate effect in preventing ear aches in healthy children. It may be an alternative to conventional therapies (such as antibiotics) to lower risk of AOM in healthy children – reducing risk of occurrence by 25% – although there is no definitive proof that it could be used as a therapy for AOM.
Diabetes.
In 2011, EFSA approved a marketing claim that foods or beverages containing xylitol or similar sugar replacers cause lower blood glucose and lower insulin responses compared to sugar-containing foods or drinks. Xylitol products are used as sucrose substitutes for weight control, as xylitol has 40 percent fewer calories than sucrose (2.4 kcal/g compared to 4.0 for sucrose). The glycemic index (GI) of xylitol is 7 if GI is 100 for glucose.
Adverse effects.
Humans.
Xylitol has no known toxicity in humans. When ingested at high doses, xylitol and other polyols may cause gastrointestinal discomfort, including flatulence, diarrhea, and irritable bowel syndrome (see metabolism section); some people experiencing these adverse effects at lower doses. Xylitol has a lower laxation threshold than some sugar alcohols but is more easily tolerated than mannitol and sorbitol.
Increased xylitol consumption can increase oxalate, calcium and phosphate excretion to urine. These effects are termed oxaluria, calciuria and phosphaturia, respectively. These are risk factors for kidney stone disease, but xylitol ingestion has not been linked to this disease in humans.
Dogs and other animals.
In dogs, 100 mg of xylitol per kg of body weight (mg/kg bw) causes a dose-dependent insulin release that can result in hypoglycemia, which can be life-threatening. Hypoglycemia associated symptoms of xylitol toxicity may arise as quickly as 30 to 60 minutes after ingestion. Vomiting is a common first symptom. It can be followed by tiredness and ataxia. At doses above 500 mg/kg bw, liver failure is likely and may result in coagulopathies like disseminated intravascular coagulation.
Xylitol is safe for cats, which tolerate even 1000 mg/kg bw ingested doses of it. It is also safe for rhesus macaques, horses and rats.
Metabolism.
Xylitol has 2.4 kcal/g (10 kJ/mol) of food energy according to US and EU food labeling regulations. The real value can vary, depending on metabolic factors. About 50% of eaten xylitol is not absorbed by the intestines in humans. Instead, 50–75% of this amount is fermented by gut bacteria to short-chain organic acids and gases, which may cause flatulence. The rest of the unabsorbed xylitol is excreted unchanged mostly in feces and less than 2 g of xylitol out of every 100 g ingested is excreted in urine. Xylitol ingestion also increases motilin secretion, which may be related to xylitol's ability to cause diarrhea. The non-digestible but fermentable nature of xylitol also contributes to constipation relieving effects.
About 50% of xylitol is absorbed via intestines. Primarily, the liver metabolizes it. The main metabolic route in humans is: in cytoplasm, nonspecific NAD-dependent dehydrogenase (polyol dehydrogenase) transforms xylitol to D-xylulose. Specific xylulokinase phosphorylates it to D-xylulose-5-phosphate. This then goes to pentose phosphate pathway for further processing.
History.
Sugar rationing during World War II led to an interest in sugar substitutes. Interest in xylitol and other polyols became intense, leading to their characterization and manufacturing methods.