ARTIFICIAL SWEETNERS

HASEEB HAKKIM MS10081 IISER MOHALI

Sweetness is one of the five basic tastes and is universally regarded as a pleasurable experience . A great diversity of chemical compounds, such as aldehydes and ketones are sweet. Among common biological substances, all of the simple carbohydrates are sweet to at least some degree.

Sucrose (table sugar) is the prototypical example of a sweet substance. Sucrose in solution has a sweetness perception rating of 1, and other substances are rated relative to this. For example, another sugar, fructose, is somewhat sweeter, being rated at 1.7 times the sweetness of sucrose. Some of the amino acids are mildly sweet: alanine, glycine, and serine are the sweetest. Foods rich in simple carbohydrates such as sugar are those most commonly associated with sweetness, although there are other natural and artificial compounds that are sweet at much lower concentrations, allowing their use as non-caloric sugar substitutes . Some other amino acids are perceived as both sweet and bitter.

Lugduname is the sweetest chemical known. It is 2,00,000 to 3,00,000 times sweeter than sucrose.

Two types of sugar substitutes are available: Bulk and Intense.

Intense sweeteners are artificial sweeteners, synthesized from a variety of starting materials. These sweeteners are intense due to their sweetness being hundreds, sometimes thousands times sweeter than that of sucrose, and their mode of action on the sweet taste bud are all similar. However, there are some clear distinctions as to their mode of action within the body.

Many bulk sweeteners have the same caloric values as sucrose, but are chosen for financial reasons/motives. Polyols, or sugar alcohols, lead the list of most common sugar replacements, although many have a fraction of the sweetness of sucrose, along with some other less desirable characteristics; the leader being their laxative effects.

Sugar substitute is the broad term used to describe any substance that replaces sugar (sucrose) as a sweetener in a food item . A sugar substitute could either be from a natural source or artificially derived. Artificial sweeteners are basically considered non-caloric. They offer a great trade-off for diabetics or individuals trying to reduce sugar and/or calories in their diet by giving the sweetness without the carbohydrates or calories. They are widely used in baked goods, soft drinks, powdered drink mixes, candy, puddings, canned foods, jams and jellies, dairy products, and numerous other foods and beverages.

Sugar substitutes are used for a number of reasons, including:

To assist in weight loss – Replacing high-energy sugar or corn syrup with other sweeteners having little or no food energy allows us to eat the same foods we normally would, while allowing them to lose weight and avoid other problems associated with excessive caloric intake.

Dental care – sugar substitutes are tooth-friendly, as they are not fermented by the microflora of the dental plaque. An example of a sweetener that can benefit dental health is xylitol. Xylitol works to prevent bacteria from adhering to the tooth surface, thus preventing plaque formation and eventually decay. The carbohydrates and sugars consumed usually adheres to the tooth enamel. Bacteria can feed upon this food source, converting it to acid waste that in turn decays the tooth structure. Xylitol cannot be fermented by these bacteria, so the bacteria have difficulty thriving, thus helping to prevent plaque formation.

Diabetes mellitus – People with diabetes have difficulty regulating their blood sugar levels. By limiting their sugar intake with artificial sweeteners, they can enjoy a varied diet while closely controlling their sugar intake. Also, some sugar substitutes do release energy, but are metabolized more slowly, potentially allowing blood sugar levels to remain more stable over time.

Reactive hypoglycemia – Individuals with reactive hypoglycemia will produce an excess of insulin after quickly absorbing glucose into the bloodstream. This causes their blood glucose levels to fall below the amount needed for proper body and brain function. As a result, like diabetics, they must avoid intake of high-glycemic foods like white bread, and often choose artificial sweeteners as an alternative.

Avoiding processed foods – individuals may opt to substitute refined white sugar with less-processed sugars, such as fruit juice or maple syrup.

Cost – many sugar substitutes are cheaper than sugar. Alternative sweeteners are often low in cost because of their long shelf-life and high sweetening intensity. This allows alternative sweeteners to be used in products that will not perish after a short period of time.

The long-term costs and risks of using artificial sweeteners -- weight gain, diabetes type II, and desensitization of gustatory (taste) sense -- outweigh this alleged benefit, however.

HOW TASTE WORKS ?

The tongue is covered with papillae - within the papillae are the taste buds. The taste buds are actually small groups of epithelial cells forming a complex interactive unit comprised of 50-150 neural receptors. These receptors are sensitive to the electrophysiological characteristics of sweet molecules ; particularly the highly polar regions of the sugar molecule making for the strong association between sugars and sweetness. Glucose specifically binds to the hetero dimeric receptors, T1R2 and T1R3, which recognize both natural and synthetic sweeteners. After this binding there is a series of neural firings in the brain that evokes memory retention about the sweetness.

It is these same receptors that molecules of artificial sweeteners are triggering as well. They are most effective at lower concentrations, which correspond well to packaging due to their intense perception of sweetness. However, at higher concentrations some molecules can also bind to another taste receptor, the TRPV1 receptor, which triggers the bitter and sometimes metallic aftertaste associated with some of the artificial sweeteners.

Human T1R2-T1R3 sweet receptor – Binding for most sweet ligands occurs on the T1R2 unit. Sugars may interact with the large N termini of both T1R2 and T1R3.

The first prominent theory dealing with chemical reception for sweetness proposed that in order to be sweet, a compound must contain a hydrogen bond donor (AH) and a Lewis base (B) separated by about 0.3 nanometers . “According to this theory, the AH-B unit of a sweetener binds with acorresponding AH-B unit on the biological sweetness receptor to produce the sensation of sweetness.”

As further research developments are taken with these artificial, intense sweeteners the conformation of these molecules are studied to determine which specific characteristics are utilized in the distinction of sweetness.

Sweeteners that are currently approved by the Food and Drug Administration (FDA) include:

Saccharin , the first artificial sweetener, was discovered serendipitously, as were most artificial sweeteners. In 1879, Constantine Fahlberg was researching the oxidation mechanisms of toluene sulfonamide while working at Johns Hopkins University in the laboratory of Ira Remsen. During his research, a substance accidentally splashed on his finger; he later licked his finger and noticed the substance had a sweet taste, which he traced back to saccharin . Since that time, a number of compounds have been discovered and used as food additives for their sweetener properties. Saccharin has been in use since 1900 and obtained FDA approval in 1970.

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Saccharin has no calories and is 300 times sweeter than sugar (FDA, 2006). It is used in such products as soft drinks, tabletop sweeteners, baked goods, jams, chewing gum, canned fruit, candy, dessert toppings, and salad dressings. It has also found some applications in cosmetic products, vitamins, and pharmaceuticals.

Synthesis of Saccharin, Remsen and Fahlberg method.

Saccharin is formed by an initial reaction between toluene and chlorosulfonic acid. It is then converted to a sulfonamide with ammonia, then oxidized to a benzoic acid and heated to form the cyclic imide.

Maumee synthesis of Saccharin.

Saccharin can be produced in various ways . In 1950, an improved synthesis was developed at the Maumee Chemical Company of Toledo, Ohio . In this synthesis , anthranilic acid successively reacts with nitrous acid (from sodium nitrite and hydrochloric acid ) , sulfur dioxide, chlorine, and then ammonia to yield saccharin:

It is are very stable for baking, but have a noticeable aftertaste when used in large amounts. Biologically, following ingestion, saccharin is not absorbed or metabolized by the body . It is excreted, unchanged, via the kidneys. Because saccharin is not metabolized, the FDA considers this compound safe.

Acesulfame-K was discovered by accident by German scientists Clauss and Jensen in 1967 while they were conducting research on then new cyclic group, dihydro-oxathiaxinone dioxide. It is ideal for tabletop use and is soluble in hot and cold beverages . An advantage of Acesulfame K is that it does not break down in heat so it can be used in cooking or baking. It can’t be metabolized or stored in the body and therefore 95% of the consumed sweetener ends up excreted in the urine.

Acesulfame K synthesis from chlorophenol.

Approved in 1998 by the FDA, it is commonly used in diabetic and low-calorie foods and is 200 times sweeter than sucrose. Also it has been found that the synergistic effect of acesulfame-K with glucose, fructose, sucrose, and sucralose increases its sweetness intensity (O’Donnell, 2005).

Aspartame was discovered in 1965 by James M. Schlatter at the G.D. Searle company. To test new anti-ulcer drugs, they had to use a tetrapeptide and to synthesize this tetrapeptide, one of the steps in the process was to make an intermediate, aspartyl-phenylalanine methyl ester. Accidentally, a small amount of the compound landed on the chemist’s hand. Without noticing the compound, the chemist licked his finger and discovered a sweet taste. After realizing it was from the powder intermediate and believing it was not likely to be toxic, he again tasted the intermediate and found it was indeed sweet aspartame. It is an odorless, white crystalline powder that is derived from the two Amino acids aspartic acid and phenylalanine.

It is about 200 times as sweet as sugar and can be used as a tabletop sweetener or in frozen desserts, gelatins, carbonated soft drinks, refrigerated and non-refrigerated ready-to-drink beverages, hot cocoa mixes, teas, breath mints and chewing gum. Aspartame has very little aftertaste but it tends to denature or lose its sweet taste when it is heated.

Phenylalanine and Aspartic Acid to yield Aspartame.

Treatment of L-phenylalanine with methanol in the presence hydrochloric acid causes an ester reaction with the acid group on the phenylalanine. The product is the methyl ester of phenylalanine.The final goal is to react the methyl ester of phenylalanine with aspartic acid to give the dipeptide amide structure. A series of reactions is required so that only the acid of the base amino acid is reacted. The acid group on the side chain is protected so that it does not react.

Two of the components of aspartame (phenylalanine and aspartic acid) are chiral, which means that they have two isomers that are non-super imposable mirror images. If the incorrect isomers are used, the aspartame molecule will not have the correct shape to fit the binding site of the 'sweetness' receptors on the tongue.

In the synthesis of aspartame, the starting materials are a racemic mixture (equal quantities of both isomers) of phenylalanine, and aspartic acid. Only the L isomer of phenylalanine is desired for use. This L isomer may be separated from the D isomer by a chemical pretreatment, followed by a reaction with the enzyme porcine kidney acylase. The final separation occurs with an acidic aqueous and organic extraction, where the L isomer is more soluble in the aqueous layer and the D isomer is more soluble in the organic layer.

MECHANISM :

Sucralose is the only non-caloric sweetener made from sugar to produce a sweetener that has no calories, yet is 600 times sweeter and tastes like sugar. It passes rapidly through the body virtually unchanged. Because of its stability, it is used in a range of products such as carbonated soft drinks, low-calorie fruit drinks, maple syrup, canned fruit, low-calorie fruit drinks, baked goods, sauces, and syrups. It pours, measures, cooks, and bakes like sugar. Sucralose also can be used as a sweetener in nutritional supplements, medical foods, and vitamin/ mineral supplements.

Sucralose is a chlorinated sugar and is produced from by a selective multi-step displacement reaction that starts with cane sugar, three of the hydroxyl groups on the sugar molecule are replaced by three chlorine atoms.

From Sucrose to Sucralose

Neotame is sweeter than some marketed no-calorie sweeteners and is approximately30-40 times sweeter than Aspartame; 7,000-13,000 times sweeter than sugar. It is quickly metabolized and fully eliminated by the body via normal biological processes. It is used in foods and beverages, including, but not limited to, chewing gum, carbonated soft drinks, refrigerated and non-refrigerated ready-to-drink beverages, tabletop sweeteners, frozen desserts and novelties, puddings and fillings, yogurt-type products, baked goods, and candies. It also can be used in both cooking and baking.

Individuals who suffer from Phenylketonuria lack or have insufficient amounts of the enzyme phenylal anine hydroxylase, required to breakdown phenylalanine. Without the presence of this enzyme, phenylalanine ac cumulates. Phenylalanine buildup can significantly alter human brain function.

Neotame is similar to aspartame, but has an extra branch added to the free amine group of aspartic acid that prevents its metabolism to produce phenylalanine that as previously discussed can cause a tolerance problem in some people. This branch, a 3,3- dimethylbutyl group, blocks the peptide enzyme from catalyzing the reaction, therefore leaving the Neotame residue intact and generating a minor amount of methanol that the body absorbs. This process yields de - esterified Neotame , the major metabolite, an insignificant amount of methanol which are are eliminated from the body with recovery in urine and feces within 72 hours .

Upon ingestion, aspartame is hydrolyzed in the intes tinal lumen into its components, aspartic acid, phenylala nine, and methanol. These components are then absorbed into the blood and each is metabolized. Methanol is quickly absorbed through the stomach andsmall intestine mucosa. There methanol is converted into formaldehyde (a known carcinogen).

The methyl ester group is readily removed by enzymes (esterases), either during the intestinal transit by calcium-dependent pancreatic esterases or after absorption by plasma esterase.

Regardless of the studies provided to and provided by the FDA, artificial sweeteners continue to receive negative press from a variety of public awareness groups. Many of these groups recommend replacement sweeteners that have a more natural origin and are not synthesized in chemical laboratories.

Common Sugar Alcohols Used as Food Additives

Sugar alcohols, or polyols, are a popular substitute in baked goods as they are considered a bulk sugar – having similar volume and texture as sucrose. Polyols are chemical derivatives of sugars that have an alcohol group (-CH2OH) instead of the aldehyde group (-CHO).

CONCLUSION

The FDA regulates artificial sweeteners and sugar alcohols, and both are considered as GRASB(Generally Recognized as Safe) or approved food additives.

Guidelines for using artificial sweeteners: It is important to note that each sweetener acts differently when heated and some leave an aftertaste when used in large amounts. The best way to begin using artificial sweeteners in home cooking is to read label directions carefully.

Using a naturally occurring ingredient to sweeten your food helps prevent harmful chemicals from entering your system. There are a range of natural options that can still be safe for diabetics and can add very little calories to food.

REFERENCES• http://www.sugar.ca/english/educators/sugarscience.cfm• www.caloriecontrol.org/sweeteners-and-lite• www.diabetes.org/food-and-fitness/food/what-can-i-eat/sugar-

alcohols.html• Aspartame Information Center. (2006). Aspartame Information Center

homepage. Retrieved July 1, 2007, from www.aspartame.org . • “Low-calorie Sweeteners and Other Sugar Substitutes: A Review of the Safety

Issues”. Manfred, Kroger. Kathleen Meister & Ruth Kava. 1995 Broadway, 2nd Floor, New York, NY 10023-5860

• diabetics – NIH http://diabetes.niddk.nih.gov/DM/pubs/statistics/index.htm