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Artificial Sweeteners

The Bitter News
In 1975, the book Sugar Blues - The Bitter Taste of Sugar by American author William Dufty, was considered daring and shocking. He analyzes centuries of history of sugar, condemning and comparing it to other drugs that have a great power of addiction, what the author calls the "white market." In 2012 the World Health Organization (WHO) declared that weight gain, obesity and mortality from chronic non-communicable diseases, such as cardiovascular disease and diabetes, is attributed to excess sugar. Merely in 2012, 38 million people died from these causes around the world. This theme was the on the cover of Essentia Magazine, in September of 2013.

Currently, some researchers support the argument that sugar added to processed products should be regulated as strongly as the sale of cigarettes and alcohol, being that this indiscriminate addition is a major contributor to the worldwide increase of people suffering from serious diseases such as obesity, diabetes and cancer. (1)

In the search for a replacement for sugar, artificial sweeteners that promise zero calories have appeared. For years this substitution was said to be perfect, and supermarket shelves have become filled with light, diet and 'no sugar' products. Recently, researches have found a link between the use of artificial sweeteners and the increase of body weight - completely opposite to the initial intended use of these substances.

After years of being used in beverages and processed foods with the purpose reducing or even completely eliminating dreaded calories, artificial sweeteners are now under fire from scientists. The current hypothesis is that they increase appetite and thus, body weight, altering the quality of diet and causing changes in gut microbiota.

Although they are considered as being safe by the regulatory agencies of certain countries such as Brazil and the USA, the toxicity and risks of these products continue to cause controversy and have divided the medical and scientific community


The concept of the gut and brain being closely linked, and that this interaction plays a role not only in gastrointestinal function, but also in certain emotional states, appetite and satiety, is quite recent. Neurobiological perceptions about this cross-talk between the gut and the brain revealed a complex two-way communication system that also ensures the proper maintenance of gastrointestinal homeostasis, digestion and has multiple effects on cognitive functions. When this communication is altered, a range of disorders may develop, such as functional and inflammatory gastrointestinal diseases, obesity and eating disorders. (2,3,4,5)

Increasing evidence suggests that artificial sweeteners distort the mechanisms of such communication in regard to satiety, what is known as "food reward", acting in a different way than sugar. Magnetic resonance imaging in normal-weight men showed that sugar intake results in the activation of this signal in the hypothalamus, alternately, a decrease in signal of the hunger center. However, the same pattern of response was not observed with the ingestion of artificial sweetener sucralose. This divergence suggests that the hypothalamic response of satiety requires the combination of sweet taste and energy content (6). Accordingly, some studies have shown that the use of some artificial sweeteners results in an increase in appetite, proving that total caloric intake is not necessarily altered by the use of sweeteners (7).


Besides affecting the communication between the brain and gut, recent research has detected another unexpected and harmful effect of artificial sweeteners: altering gut microbiota that results in dysbiosis. In other words, causing an imbalance between beneficial bacteria and pathogens present in the human gut, is harmful to one’s health. Although these are preliminary studies, the results, recently published in the renowned and respected journal Nature, indicate that the widespread use of these food additives should be reassessed and that non-caloric artificial sweeteners "may have directly contributed to enhancing the exact epidemic that they themselves were intended to fight." (8)

The chance that artificial sweeteners may enhance metabolic disorders such as diabetes is a real blow to those who have followed dietary recommendations and have replaced sugar. In a study conducted by the Department of Food Science of the University of Copenhagen, Denmark, researchers examined the differences between gut flora, or microbiota, of diabetic and non-diabetic adults. Results indicate that type 2 diabetes in humans is associated with compositional changes of gut microbiota, and that the level of glucose tolerance should be considered as the link with metabolic diseases such as obesity, seeking strategies to control these diseases by modifying gut microbiota (9).


Artificial sweeteners may also enable something that psychologists call cognitive distortions. Exchanging a common soda for a diet drink now means permission for a slice of chocolate cake later. This results in the notion that one can eat more food than one really should. Psychology is a factor, however, physiology can also be altered, reports Swithers (10), study author of High-intensity sweeteners and energy balance published in 2010 in Physiology & Behavior journal.

Replacing sugar with artificial sweeteners may not have a positive influence in the control of appetite, since, for example, the artificial sweetener aspartame, can eventually promote appetite inhibition. This effect demonstrates that not all sweeteners result in exacerbation due to release a metabolite. On the other hand, the intake of the same sweetener may reduce the enjoyment of sweetness, which increases the desire for sweets and carbohydrates, increasing appetite and consequently higher energy consumption and possible weight gain (11).


After saccharin, aspartame is the second most widely used artificial sweetener in the world (12). Thirty years after its approval, security issues on the use of aspartame continue to be studied exhaustively. In general, the assessed security issues are related to the toxicity of its metabolites (phenylalanine, aspartic acid and methanol), which cause neurotoxic alterations, an onset of serious diseases. (13,14)

A study published in 2008 by the European Journal of Clinical Nutrition aimed to investigate the direct and indirect cellular effects of aspartame on the brain. It was found that aspartame disturbs the metabolism of amino acids, protein structure and its metabolism, the integrity of nucleic acids, neuronal function, and alters concentration of catecholamines in the brain. It was also reported that, among others, aspartame and its deritative products cause stress in the nerves, which indirectly causes a high rate of neuronal depolarization (15).

Research conducted by Dr. Soffritti in 2005, presents findings of a long-term study on the carcinogenicity of aspartame. Results showed a statistically significant increase of leukemias, lymphomas and other types of cancer in rats. Therefore, the sweetener, even when administered at lower levels than the acceptable daily dose (40 mg/kg body weight in the European Union and 50mg/kg body weight in the United States), proved to be a carcinogenic agent capable of inducing malignant tumors (12).

In his book "Aspartame Disease: An Ignored Epidemic", H. J. Roberts reveals information on 1,200 cases that presented adverse reactions to the sweetener as were reported to him. According to the book, in 1998 products containing this substance were the cause of 80% of the complaints made to the Food and Drug Administration (FDA) on food additives, which include: headache, dizziness, mood swings, vomiting or nausea, abdominal pain and cramping, abnormal vision, diarrhea, seizures, memory loss and fatigue (16).


Sodium cyclamate

Discovered by chance in 1937, cyclamate was initially marketed as an artificial sweetener for diabetics and subsequently added to the list of substances recognized as safe by the FDA. In the 60's there was an increase in the consumption of artificial sweeteners in the country due to the combination of cyclamate with saccharin (17).

In the mid 60's, the authors of the Studies on synthetic sweetening agent. VIII. Cyclohexylamine, a metabolite of sodium cyclamate, Kojima and Ichibagase, found that sodium cyclamate was not excreted in the urine, but instead could be metabolized as cyclohexalamine, considered a carcinogen. In 1969, the link between cyclamate and saccharin, was interpreted by the FDA as inductive of bladder cancer in mice. Based on these studies, its use was banned in the United States. Nevertheless, in 1977, the Joint Expert Committee for Food Additives (JECFA), approved the use of sodium cyclamate as a sweetener in foods and beverages in more than 40 countries, including Brazil (17).


The solution that brought new problems

In 1976, the artificial sweetener sucralose (sucrose containing three chlorine atoms), unlike the majority of sweeteners that have been discovered by chance, was the result of a major research program involving the British sugar group Tate & Lyle, together with a team of researchers at the University of London, led by Professor Hough (18).

Studies that associate the use of sucralose with changes in gut microbiota, carcinogenic effects and neurologic abnormalities (19,20,21,22) are periodically published in renowned media. Despite the evidence showing the bitter truth behind its use, sucralose is still permitted worldwide.


On the one hand, there are many studies, past and recent, which reveal the dangers of sugar and state that its consumption should be reduced. On the other hand, a growing number of research warn us against the harmful effects of artificial sweeteners. So, do we have a choice? Following the current worldwide trend, (7) returning closer to nature and looking for the less toxicity is proving to be the better option.


Polyols (or sugar alcohols) comprise a group of slow digestion carbohydrates derived from the hydrogenation of sugar sources found naturally in plants. Its use as a sugar substitute and its multiple benefits such as not causing tooth decay, having a low glycemic index (does not produce insulin spikes) and low caloric content, are some of its characteristics. Among the more common types are: xylitol, erythritol, maltitol, and sorbitol.


The discovery of xylitol in the nineteenth century is credited to two researchers, Hermann Emil Fischer in Germany, and M. G. Bertrand in France. Its extraction comes from fibrous vegetables, fruits and corn, the latter being currently the main source of extraction. In the mid-1950s, researcher Touster and his colleagues concluded that xylitol is formed in the human body in about 15g a day through normal glucose metabolism (36).

Being well tolerated by the gastrointestinal tract, xylitol can be used in the same proportion as sugar and, in contrast, contains about 40% fewer calories. Nevertheless, these calories have a low glycemic index; they will only be released in the body as it is digested in the liver by the hepatic enzyme xylose (37). But be careful not to give products containing xylitol to dogs or cats, because these animals do not have this enzyme, and thus cannot digest it.

Recommended for patients with diabetes and autism, it can also be used for weight control as it helps reduce gastric emptying, has low GI and keeps levels of insulin and sugar ideal, mainly due to its metabolism being independent. Such behavior increases satiety and decreases binge eating (50). Other benefits include the reduction of oxidative damage in muscle and blood cells, increased post-workout recovery due to its constant conversion into glucose (energy) and glycogen (storage) - which is why its use between meals works to maintain a constant flow of energy - and helps in maintaining gut microbiota (38).


Erythritolis found naturally in fruits such as pears, melons, grapes, as well as in foods such as mushrooms and other derivatives from fermentation such as wine, cheese and soy sauce. It is a sweet white crystalline powder without aftertaste, similar to sucrose, and approximately 70% as sweet. The caloric value of erythritol is 0.2 cal/g (so little that is considered by many as having zero calories). Also, its high digestive tolerance distinguishes it from other polyols (25,39,40).

Rapidly absorbed in the small intestine and eliminated without alteration through the kidneys (24 hours), erythritol is considered exempt of laxative side effects, which are often associated to the excessive consumption of polyols (41).


Maltitol is the polyol family member most widely used due to its striking similarity to sucrose - about 90% as sweet as sugar, with significantly reduced calories - except for the fact of it not having good caramelization (25).

Produced by hydrogenation of maltose, which is obtained from starch, maltitol is absorbed slowly. It undergoes hydrolysis in the intestine and transforms into sorbitol and glucose prior to absorption. The reduced caloric value of maltitol (2.1 kcal/g) is also consistent with the goal of weight-control (42).


Sorbitol is a polyol found in various food products and is about 60% as sweet as sucrose, but with a third of the calories. It was discovered by a French chemist in 1872 in the rowan fruit (Sorbus aucuparia), but it occurs naturally in many other fruits and berries. Currently, it is commercially produced by the hydrogenation of glucose and is available in liquid form and crystals, also being used in pharmaceutical and cosmetic products (25).

From a pharmacological point of view, sorbitol stimulates the motility of the gallbladder, favoring emptying and the formation of bile. Bile acts in the digestion of fats and absorption of nutrients from one’s diet while passing through the intestine. However, people with a tendency to diarrhea need to be careful.


Considered safe and having been consumed for a long time, vegetable sweeteners offer a natural source alternative to replace artificial sweeteners or the various forms of sugar.


Stevia has a long history of safe usage in food and beverages throughout the world (43). Extracted from Stevia Rebaudiana, a plant native to the Amambay Mountains on the border of Brazil with Paraguay, it was discovered in 1905 and industrialized in 1970 (43). Quite common in Japan – it represents about 40% of the country’s market of low-calorie sweeteners (43). In 2010, the European Food Safety Authority (EFSA) published a statement on the safety of stevia, and during many years the Joint FAO/WHO Expert Committee on Food Additives (JECFA) reviewed the safety of steviol glycosides (originating from the stevia plant), subsequently establishing 12mg/kg body weight per day as a safe intake dose. Considering the toxicity data available in several in vitro and in vivo studies of animals and humans, the panel concluded that stevia complies with the specifications of the JECFA: it is not carcinogenic, genotoxic or associated with any reproductive or developmental toxicity (43). Due to its high sweetening power, about 400 times higher than sugar, the amount used, for example to sweeten coffee is approximately 30 milligrams - far from the limit set by JECFA (the daily equivalent of 840mg of high purity stevia, considering a person of 70 kg).


The Katemfe fruit, originating in West Africa, has high sweetening power, flavor enhancing and aroma in foods and beverages. It has been found that this fruit contains a long-chain vegetable protein, which is responsible for its sweetening power –thaumatin. This protein has unique properties and benefits: it is the sweetest substance in nature –about 2000 times sweeter than sugar, as well as having the ability to mask any undesirable bitter aftertaste (44).

Several scientific and toxicological studies attested that thaumatin does not cause any adverse health effects and can be consumed by everyone, including diabetics, phenylketonuria (a rare genetic disorder characterized by a defect in the phenylalanine hydroxylase enzyme), and pregnant women. Since it is a protein, its metabolism occurs naturally as would any vegetable protein.


The availability of a variety of sweeteners from more natural sources is a benefit to the consumer, being that, in this way, sugar can be replaced in foods and beverages in order to reduce calories as well as their harmful effects, while maintaining the attractive sweet taste in food products. When choosing the type of sweetener that will be introduced into one’s diet one should consider its origin and what it can lead to in the long term. Taste, learn and enjoy.

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