Long before we could simply buy foods from a grocery store, our ability to detect the presence of sugars in foods was critical to our survival as a species. We as humans have evolved to recognize sugary foods as tasting "good," because they are nutrient dense (high in calories) and "good" for us to eat, though today that's not entirely true. Rather, sugary foods used to be good for us to eat long ago when we were hunting and gathering in the wild. Back then, we needed the extra calories to survive. Today, however, many of the foods that we eat are very nutrient dense and have many calories in the form of fat, protein, or sugar. Sugar is far more prevalent now that we know how to refine and process it on an industrial scale. Most of us don't really need to gather fruits to get sugar in our diet. We can just buy a Snickers bar off the shelf at any convenience store.
This abundance of sugar has made life easier and tastier, but it has also come at a cost. Increased sugar consumption contributes to the world-wide epidemics of obesity and diabetes. As a result, there has been a lot of research effort into the development of artificial sweeteners and other products than can cut calories from food. Sugar substitutes have the potential to positively impact world-wide health and save billions of dollars of healthcare costs per year. Obesity leads to cardiovascular and liver diseases as well as type 2 diabetes mellitus.
There are also less altruistic but equally valid reasons for developing artificial sweeteners. Another major goal is to cut costs in food and beverage manufacturing. Consider a product like soda, where the major components are water and sugar, often in the form of high fructose corn syrup. An alternative to sugar that tastes the same but costs less to produce could save companies millions or billions of dollars per year.
When most people think of artificial sweeteners, we first think of diet soda, which is sweetened by artificial chemicals such as apartame, acesulfame potassium (acesulfame K), and/or sucralose. Many of the products that we consume also contain artificial sweeteners known as sugar alcohols, though they don't get a lot of attention and many people have probably never heard of them. Let's explore a bit about sweet taste, sugars, and sugar alcohols after the jump....
|Three common monosaccharides (shown in linear form)|
|Glucose, fructose, and sucrose, shown in ring form|
But the first place that your body detects sugars in your mouth, through the sweet taste receptors on the surface of certain cells on your tongue. There's only one type of sweet taste receptor that we know of, but it can detect multiple types of monosaccharide and disaccharide sugars. The ability of the sweet taste receptor to detect multiple types of sugar structures is going to be important when we discuss artificial sweeteners.
When the sweet receptors detect sugar, they stimulate taste cells to send a signal to nerves that connect to your brain. The exact neural pathways that sweet taste activates in your brain are complex, but they include reward pathways that affect our responses to sweet taste. Studies have suggested that sweet taste may activate similar reward centers of the brain as those that are activated by opioid drugs or by alcohol in the brains of alcoholics. This serves to reinforce our preference for sweet tastes. Genetic variations in sweet taste receptors and/or neural pathways in the brain may create differences in individual preference for sweet foods similarly to how genetic differences are thought contribute to susceptibility to alcoholism or drug addiction. The neurology and psychology of sweet taste is an active area of research, because sweet taste preferences may have important implications for sugar consumption and thus obesity or diabetes.
Creating an artificial sweetener is a pretty cool concept when you think about it. The evolutionary purpose of sweet taste is to identify nutrient-rich foods like fruits. The goal of an artificial sweetener is to trick your body, specifically the cells with the sweet taste receptors on your tongue, into thinking something is nutrient dense by activating the sweet receptors on the sweet-taste-responsive cells on your tongue. In reality though, the ideal artificial sweetener is a molecule that our bodies can't metabolize very well or can't absorb and thus can't derive much energy from.
|Two artificial sweeteners that are very different in structure from sugars|
|Soda can showing aspartame and acesulfame K as ingredients|
|Three chloride atoms distinguish sucrose from sucralose|
Sucralose was first approved for use in the US in 1998, and its use has exploded since then. Thousands of sweet beverages, candy, and baked goods contain sucralose, often under the brand name Splenda®. Many people say that sucralose has less of an "artificial" or "metalic" flavor than some other artificial sweeteners. Part of this is due to cross-reactivity of some artificial sweeteners with other types of taste receptors. For example, aspartame is also a weak activator of some types of bitter taste receptors, and thus it can impart undesirable tastes along with the sweetness. Sucralose has much less cross reactivity with other receptors because its structure is much more similar to a real sugar. Also, because it is sweeter than many other artificial sweeteners, much less of it can be used to achieve the desired sweetness.
While the safety of some "non-nutritive sweeteners" like aspartame has been disputed by some, there is little hard scientific or clinical evidence to support any toxicity in humans at present. One health concern is that the use of non-nutritive sweeteners can lead to increased consumption of calories by other means. For example, someone may feel that drinking a diet soda gives them the dietary leeway to eat a candy bar, too, and thus they end up consuming even more calories in the end. In fact, some studies have linked consumption of "high-intensity" sweeteners like aspartame or sucralose is correlated with increased levels of diabetes and obesity, which may be due to alterations in eating patterns or the ability to interpret or predict the calorie content of foods that due actually contain sugar. In other words, drinking soda sweetened with hyper-sweet aspartame make make a candy bar sweetened with real sugar not seem so sweet, which may make people think candy bars aren't so bad and that they can eat more. More research is needed to really tease out how artificial sweeteners affect us, but the American Heart Association and American Diabetes Association stress that limitation of added dietary sugars is a key component of diabetes, obesity, and cardiovascular disease management; non-nutritive sweeteners may indeed have a benefit if they are used in this role as part of a well structured diet.
|Sorbitol is made by the reduction of glucose|
Some sugar alcohols are produced naturally, but most of the ones used today are chemically derived from sugars. Thus, most sugar alcohols actually cost more to produce than sugars. Also, because their sweetness is often not as "high intensity" as other artificial sweeteners like sucralose, more sugar alcohols have to be used to achieve the same relative level of sweetness as other compounds like sucralose and aspartame. While not as "cost effective" per se, the use of sugar alcohols has many other benefits that we'll discuss below.
Xylitol is one of the most common sugar alcohols used. Because it is almost twice as sweet than sorbitol, it is a more attractive ingredient because less of it needs to be used. Xylitol is considered to be "isosweet" (the same sweetness; iso = the same) as sucrose, while sorbitol is only 50-80% as sweet as sucrose. Xylitol naturally occurs in very small amounts in certain fruits and vegetables as well as in our own bodies as an intermediate (or a short-lived product that gets converted into something else) in a biochemical pathway called the glucuronic acid cycle, also called the uronic acid pathway. The glucuronic acid cycle is important because it converts glucose into a reactive form of glucuronate (UDP-glucuronate) that can be used to detoxify foreign substances in the liver as well as to build or break down a class of chemicals called mucopolysaccharides (also called glycosaminoglycans) such as heparin and hyaluronic acid.
Most of the xylitol found in food and pharmaceuticals is made from xylan, a polysaccharide made from long chains of a monosaccharide called xylose that is found in trees and other plants. Xylitol has been approved in the US as a "food additive" for special purposes since 1963, but its use is limited, because it is more expensive to produce than other artificial sweeteners. However, it is a mainstay of sugar free gum and mouthwashes, and has beneficial effects for oral health that we'll describe later on. In other countries, xylitol has more widespread use. In some areas, sugar substitutes that are sold for baking that are nearly 100% xylitol.
|Hermann Emil Fischer|
For many decades after xylitol was discovered, no one was very interested in it. It wasn't until the 1960s that the use of xylitol as a food and drug additive began to get serious study, and the use of xylitol has exploded in recent years. Xylitol is used as a sweetener in products such as sugar-free candy and gum, but also in other "low carb" or "low calorie" products such as muffins and cookies. Additionally, it is found in a countless number of pharmaceuticals, from cold medications to toothpastes to mouthwashes.
One of the main benefits is that sugar alcohols like xylitol and sorbitol (another common ingredient in sugar-free gum) are not able to be fermented by bacteria in the mouth. Xylitol may actually inhibit the ability of these bacteria to metabolize other sugars. When one of the most common oral bacteria, Streptococcus mutans, tries to metabolize xylitol, enzymes in the bacteria phosphorylate it to xylitol-5-phosphate; different bacterial enzymes then convert xylitol-5-phosphate back to xylitol, creating a futile "energy wasting" metabolic cycle. Xylitol may also inhibit the fermentation of Streptococcus mutans and other bacteria by inhibiting key bacterial enzymes as well. Thus, using xylitol or sorbitol as a sweetener does not contribute to and may actually inhibit bacteria growth, plaque build-up, and formation of cavities. Interstingly, though, because of this, xylitol cannot be used as a sweetener in products containing yeast, like sweet breads, as xylitol is also a potent inhibitor of yeast fermentation and growth.
Xylitol also absorbs heat as it dissolves in water, an endothermic (or heat absorbing) reaction. As a result, products with crystalline xylitol can also create a pleasant cooling affect that fits very well in a minty chewing gum or mouthwash. Furthermore, xylitol may be able to associate with calcium ions and contribute to tooth remineralization, possibly giving it an added benefit in dental products like gum and toothpaste. Further research is needed to more fully understand this role of xylitol.
For the most part, xylitol is extremely safe in humans. Xylitol is very slowly absorbed in the human intestine. This is because there is no "natural" transport system for you to absorb the xylitol. None of the proteins involved in sugar transport across the intestinal epithelium recognize xylitol as efficiently as they recognize naturally occurring sugars. When you ingest xylitol, you typically only absorb about one third of it, with the rest being metabolized by the gastrointestinal microbes that populate your gut. Through fermentation, they turn the xylitol into gasses (carbon dioxide, hydrogen, and methane) as well as short chain fatty acids that you can then more efficiently absorb. However, because of the poor and slow absorption of xylitol, high doses (less than 50 grams for the average person) can cause diarrhea because it draws water out of the intestines through osmosis. Also, the fermentation of xylitol and gas build up can create bloating in some people if enough xylitol is ingested.
The xylitol that you do absorb is converted in the liver first to D-xylulose and then to fructose-6-phosphate, which your body can then more readily metabolize to glucose and derive energy from. A given amount of xylitol has approximately 40% fewer calories than an equal amount of sucrose. However, the incomplete absorption of xylitol also contributes to lowering its calorie content even further. Also, because the absorption of xylitol and conversion of xylitol to glucose is slow in humans, the ingestion of xylitol does not cause a detectible increase in blood glucose as see when natural sugars like sucrose or glucose are consumed. The glycemic index is a relative measure of how fast blood glucose levels increase after ingestion of certain foods. The glycemic index of xylitol is over 10 times lower than that of glucose. Because of this, xylitol does not cause significant levels of insulin secretion in humans.
All-in-all, the discovery and use of xylitol has had pretty positive effects for humans. However, there is a hidden danger to xylitol that many people don't know about. Xylitol is extremely toxic to dogs, as we mentioned in a previous blog post. Unlike humans, dogs can rapidly absorb xylitol in their gastrointestinal tract. Peak absorption occurs after only 30 minutes. Once ingested and absorbed by the dog, xylitol stimulates insulin secretion that is about 6 times greater than that seen after ingestion of an equal amount of glucose. Ingestion of large amounts of xylitol (greater than 0.1 gram per kilogram of bodyweight) can cause rapid-onset lowering of blood sugar (hypoglycemia) due to insulin release in the absence of a real increase in blood glucose. Insulin secretion can start after as little as 20 minutes after ingestion, though it depends on the type of product ingested by the dog and how much the dog actually chews it, as slow release of the xylitol can lead to symptoms of hypoglycemia or liver toxicity taking as long as 12 hours to appear. The exact reason why xylitol stimulates insulin secretion in dogs (as well as cows, goats, and rabbits) but not humans (or rats and horses) is unknown, but some studies have suggested that xylitol directly stimulates pancreatic beta cells of dogs to secrete insulin.
Higher doses of xylitol (greater than 0.5 gram per kilogram of bodyweight) can also cause liver damage (hepatotoxicity) in dogs. The exact mechanism of this is also not very well understood, though it is thought that reactive byproducts (free radicals or reactive oxygen species) produced during the metabolism of xylitol may be damaging to liver cells. Also, as liver cells try to break down xylitol, these cells may become depleted of ATP and energy, a condition that can lead to necrosis, a type of cell death.
It is not surprising that the curiosity and indiscriminate appetite of dogs results in dogs accounting for over 70% of potential poisoning cases seen by vets. If you have a dog and suspect that he or she ate something containing xylitol, the safest thing to do is call your vet, even if there are no immediate symptoms. Some dogs require monitoring to make sure that delayed-onset symptoms do not appear. When there are symptoms (vomiting, decreased blood glucose, lethargy, altered liver enzyme levels, or even seizures), vets can treat the dogs and the prognosis is good. We previously discussed several food that are toxic for pets in a previous blog post, and likewise dog owners have to be aware of the danger of xylitol to dogs and be aware of what their dog eats so that if their dog eats something with xylitol, they can let their vet know that this could be the cause of their dogs symptoms.
Cakes, cookies, gum, or any other product made from xylitol are potently toxic to dogs. There's not good evidence that xylitol has the same type of toxicity in cats, though there are case reports of cats developing hypoglycemia after ingesting xylitol. While xylitol may or may not be safe for cats, the best strategy is still to keep xylitol-containing products away from all pets. Synonyms for xylitol that might be used on some labels include Eutrit, Kannit, Klinit, Newtol, xylite, Torch, or Xyliton. While the science behind xylitol and its use in food and pharmaceuticals has may health benefits for humans, we also have to be aware of the potential danger to our furry four-legged friends.
Text © 2013 TheMadScienceBlog.com; Images are public domain.
Sources and Further Reading
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