Artificial sweeteners are to be found everywhere. From Diet coke to dental chewing gum, and from sugar free barbecue sauce to many dietary supplements on the market. The problem arises with the discovery of the correlation between sugar and weight gain. With the increasing levels of obesity and diabetes in the population, people are trying to lose weight and therefore cut down on their consumption of calories, saturated fats, and also sugars. It is therefore that a great deal of low calorie, no sugar products in order to accommodate this demand for diet products. Starting with the discovery of Saccharine in 1879, dozens of artificial sweeteners were created to sweeten foods without having the bad side effects of real sugar. Unfortunately, it was soon discovered that not all of these sweeteners were very healthy for the body. The chemical structure of these sweeteners were artificial, and therefore difficult for the body to digest and possibly co- responsible for illnesses such as cancer. It is therefore that it became of crucial importance to test the carcinogenic effect of these substances. With hundreds of millions of people taking these sweeteners on a daily basis, strict research needed to be conducted.
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Aspartame, today probably the best known artificial sweetener, is a non- saccharide sweetener two hundred times sweeter than sugar that is added to a lot of different food and beverage products. It was first synthesized in 1965 as a methyl ester of phenylalanine and aspartic acid dipeptide. In 1980, the USDA (United States Food and Drug Administration) approved of its use. Nonetheless it's first negative side effect was discovered in people with the disease phenylketonuria. This genetic disorder causes a deficiency of the enzyme phenylalanine hydroxylase in a person, making it impossible for them to digest the amino acid phenylalanine. Since aspartame of course contains this amino acid it can have severe side effects on people with PKU.
Nonetheless, studies were soon to be conducted on the possible carcinogenic effects of this artificial sweetener. The interest of the public needed to be satisfied, as even today most people try avoiding aspartame due to its supposed negative side effects. In an article on physical and nutritional health and their link to cancer, a team of researchers from the American cancer society constituted that there was no correlation between aspartame and cancer (American Cancer Society). Backing up this idea is a multitude of research such as a study done by an Italian research team lead by Dr S. Gallus where 14,000 patients in an Italian hospital (7,000 with cancer 7000 without) were interviewed on their consumption of aspartame and other artificial sweeteners. The conclusion was that both aspartame as well as saccharin did not correlate with the patients' obtaining of cancer (Gallus et. al). On top of that, another study done by a team led by James G. Gurney proved negative in correlation. This study was conducted because certain dietary constituents when nitrosated in the stomach could create the carcinogenic N- Nitroso compounds. Research done by Shepard et al. however showed only a weak correlation between cancer and the nitrosated compouds of aspartame. Nonetheless, a few studies such as that of Morando Soffritti et al. showed an increase in lymphomas and leukemias in rats. This could be generalized to humans when the researchers discovered that the cancer could be related to methanol, a metabolite of aspartame, which is metabolized to formaldehyde and then formic acid in both humans and rats (Soffritti et al.). This experiment came as a bit of a shock, yet the overwhelming amount of studies proving there to be no link between cancer and aspartame made for the USDA to keep the substance legal nonetheless.
Saccharin is also one of those sweeteners that has been heavily criticized by researchers and the public for not being a possible carcinogenic agent. The basic component of saccharin is benzoic sulfimide, which is extremely sweet but due to its metallic essence leaves a bitter and metalloid aftertaste. Today it is most commonly synthesized through a reaction between anthranilic acid, sulfur dioxide, chlorine, and ammonia. Saccharin is a legal substitute in the united states, largely due to the severe pressure of soft drink companies and the public to keep it legal, however is not legal everywhere in the world. Being the oldest existing sugar substitute, it is also the best researched.
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A significant amount of studies conducted especially in the 1960s and 1970s demonstrated a large increase in bladder cancer among rats and thyroid cancer in mice. In particular a study done by Taylor et al. showed that at increased saccharin intake levels, rats suffered a larger amount of neoplasm of which a majority was malignant (Taylor et al.). A later study by Cohen et al. showed that when ascorbic acid (Vitamin C) was fed to rats in similar doses to that of saccharin, the was an increase in the rats' neoplasm as well. It turns out that rodents have a high urine osmolarity, which increases the formation of calcium phosphate containing crystals in the epithelium of the bladder. This being cytotoxic to the bladder causes the abnormal growth and increased cancer risk (Cohen et al.). A study done by Jensen et al. on people alive during the years 1941-1945, when saccharin consumption was at its highest also revealed no increased incidence of bladder cancer. Since the year 2000 Saccharin is no longer on the US National Institute of Environmental Health Sciences list of suspected human carcinogens. Nonetheless, research is still in progress.
Acesulfame Potassium is the an artificial devoid of calories and is therefore a favorite in protein powders and other muscle building products. Discovered in 1967, it had a chemical structure of a potassium salt consisting of methyl, and oxathiazine dioxide. Due to its slightly bitter after taste it is often combined with other sweeteners, but is reputed for its superior stability under heat, making it a good sweetener for baking. Being a relatively new sweetener like many others, there has been hardly any incriminating evidence provided by researchers. Even though the USDA discarded this little research, critics still argue that there has been hardly enough research done to ascertain this product's safety.
Acesulfame Potassium (www.wikimedia.org)
Research conducted by Mukherjee and Chakrabarti showed no toxic side effects of acesulfame potassium on rats in low doses. Nonetheless, at higher doses the rats showed chromatid abberations. The researchers also stated that research previously conducted by Mayer et al. on Chinese hamsters revealed a number of "micronucleated polychromatic erythrocite an chromosome abberations" (Mukherjee & Chakrabarti). They cautioned people for the excessive use of this relatively new product. Nonetheless, organizations such as the USDA, FDA, and the UK handbook of pharmaceutical excipients all discard this research stating that "Long-term feeding studies in rats and dogs showed no evidence to suggest acesulfame potassium is mutagenic or carcinogenic" (UK handbook of parmaceutical excipients).
Sodium Cyclamate is the least functional of the artificial sweeteners. It is prepared as a sodium or calcium salt of cyclamic acid, which is generated by the sulfonation of cyclohexylamine by reacting it with sulfamic acid or sulfur trioxide. This is one of the most dubious of the sweeteners, and has been banned in most countries.
In 1970, a study done by Wagner et al. showed that deer mice avoided cyclamate solutions of all kinds in favor of normal water, even though the cyclamate solution was obviously sweeter. Between water and glucose solutions, the mice did go for the sweeter solution every time. On top of that, people also characterized the taste of cyclamate as being "thin" or "metallic" (Wagner et al.). The only reason people seemed to choose cyclamate over glucose was because of its zero calorie value. According to A.G. Renwick, Cyclamate is converted int cyclohexylamine, which is a metabolite reported to be quite toxic. According to further study by Sharratt et al. cyclohexylamine caused testicular atrophy and impairment of spermatogenesis in rats (Sharratt et al.). Nonetheless, studies on humans and cancer cases since 1970 have led many organizations so far not list cyclamate to be carcinogenic, and has therefore still no place on the list of carcinogens.
Xylitol is one example of the large group of sugar alcohols. It is a five sugar carbon and can be encountered in fruits and vegetables such as corn husk, oats, and berries and is therefore found naturally and organically. It is just as sweet as sugar, but also has two thirds of the caloric value, which is far more than any of the other zero caloric value sugar substitutes. It is used as a sweetener (especially in candy and chewing gum) as well in various medical products treating osteoporosis and even for increasing neutrophil counts in people in order to treat infections.
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Xylitol is metabolized as a carbohydrate, and is thus oxidized into carbon dioxide and water. One third is dehydrogenized within the liver, and the rest of it goes into the intestinal tract where certain bacteria turn it into short chain fatty acids (livestrong.com). Xylitol is even naturally produced by the body, and can therefore be safely ingested. Large amounts can nonetheless be very uncomfortable for people, and even deadly for dogs. Xylitol is one sweetener where it seems that when consumed in a reasonable manner, one need not worry about its carcinogenic effects. Nonetheless, Xylitol has a problem of its own. In an experiment on 8 dogs, Dunayer et al. discovered gastrointestinal tract hemmorages, lethargy, and vomiting in the dogs when they ingested a large amount of xylitol. It turned out that dogs had a sensitivity to it which caused them to have an extreme increase in blood insuline levels. When they tried to generalize this to humans on high concentrations of xylitol, the trial had to be terminated after three days because "subjects complained of right upper quadrant pain, nausea, headache, and vertigo" (Dunayer et al.). The researchers measured high levels of bilirubin, and high activities of the hormones ALT, AST, ALP, and LDH. This is of course bad for humans, but also for the dogs, as xylitol is being used more and more in dog food products as an artificial and "healthy"Â sweetener. In order to avoid stomach cramps and diarrhea, it is important to limit one's consumption of sugar alcohols.
Stevia is actually a genus of some 240 species of herbs and is a part of the sunflower family. One particular species called Stevia rebaudiana is which actually produces the sweetener commonly known as "sweet leaf" or just "stevia". Crystalization and separation technologies are used to separate different glycoside molecules so that a producer can isolate the sweet substances. Stevia possibly can even have positive effects, but has been banned in many countries as well precisely for its possible carcinogenic effects.
The official stevia website (stevia.net) states that the stevioside and rebaudioside breakdown product steviol was converted into a mutagenic compound quite well in the liver of rats which can cause a mutation in the cell DNA leading to the uncontrolled cell proliferation which is cancer. Nonetheless, this has only been tested in laboratories on animals, and it is till not known for sure yet whether stevia is truly carcinogenic. This is why it is still widely used in Japan and Latin America. Even in the United States the stevia rebaudioside A version is once again accepted.
In the end, most artificial sweeteners are still on the market today because there is too little evidence confirming the carcinogenic effects of any of the above products. Nonetheless, these products must be approached with caution and moderation as any other, especially due to the studies that did point in the direction of their carcinogenic effects. The fact that any living organism whatsoever can deduct cancer from an overdose of a sweetener says something about the chemical nature of these products. They were created artificially in laboratories, and were indiscriminately avoided by rats even in favor of the less sweet taste of water. Even though it is safe to consume these substances to a certain extent, it is all the more important to stress the word "artificial", and the effect that something man made and unnatural can have on our metabolism.