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Artificial Sweeteners: a Review Kranthi Kumar Poshala School of Health and Life Sciences, Teesside University, England

Artificial Sweeteners: a Review Kranthi Kumar Poshala School of Health and Life Sciences, Teesside University, England

ISSN 2321 3361 © 2020 IJESC

Research Article Volume 10 Issue No.10

Artificial Sweeteners: A Review Kranthi Kumar Poshala School of Health and Life Sciences, Teesside University, England

Abstract: gained a bitter name regards to health. Consumption of more involves risk of more calories which leads to diseases like obesity, and cardiovascular problems in human body. These days which is sugar free acquired much more reputation because of their low or no calorie content. So as a result many food industries use different low calorie artificial sweeteners instead of sugars. Food and Drug Administration (FDA or USFDA) accepted the use of six sugar substitutes (, saccharine, , , acesulfame-k and ) safe human consumption. and extract from swingle fruit have recently discovered and added to the list of nonnutritive sweeteners. These artificial sweeteners or sugar substitutes are extensively applied in the fields of processed , dairy and therapeutic industries. The main aim of this review is to discuss the different types of artificial sweeteners, their history, synthesis, , uses, , therapeutic use, nontherapeutic use, health benefits and toxic effects.

Keywords: Artificial sweeteners, diabetes, nonnutritive sweeteners, obesity, sugar substitutes.

I. INTRODUCTION Many of Non-nutritive sweeteners (NSSs) have been manufactured, but intense research and development in natural In the recent and current years people are very much conscious NSSs is expanding (Toews et al., 2019). about their health and showing a great concern on quality of life. Imbalanced consumption of excess calories and saturated is Non-nutritive sweeteners (NSSs) vary from sugars not only in leading most of the population to obesity. their properties of , but also in metabolic rate and physiological processes (Ferrazzano et al., 2015). Obesity became a notable subject all over the world (Serdula et al., 1999, Scott et al., 2006). Studies show that most of the Non-nutritive sweeteners (NSSs) are sweeter than and individuals are disturbed by overweight and well-being have very few calories. All of these sweeteners are distinctive in associated consequences (type II diabetes) (Sorensen et al., intensity and persistence (Mortensen, 2006). 2003). In few situations, the word “artificial sweeteners” is considered The frighten prevalence of obesity has been impute to as a synonym for Non-nutritive sweeteners (NSSs). diversification of social-economic components like food habits and lifestyle (Story et al., 2008). In this review we use NSSs as artificial sweeteners / Artificial sweeteners (non-nutritive sweeteners) are sugar substitutes Responsibility on sugar consumption have taken into which are several times sweeter than normal sugar. consideration from 1970s where obesity outbreak has started (Kavey, 2010). These days the ultimate target of diabetes is to These food additives gives sweet taste same as sugar while control the or sugar levels in blood. having no making it no calorie sweeteners (Whitehouse, Boullata and McCauley, 2008). By raised interest of customers in reducing sugars in foodstuffs having non-sugar sweeteners (NSSs) instead of simple sugars Non-nutritive sweeteners (artificial sweeteners) are produced have become more popular (Sakurai et al., 2013). from extracts of plants or by safe chemicals (Wani and Bhat, 2019). Sweeteners are categorized as nutritive and non-nutritive sweeteners. Nutritive sweeteners are further classified into These sugar substitutes are extensively used in processed foods sugars, modified sugars, sugar alcohols and natural caloric (powdered , soft drinks, carbonated beverages, baked sweeteners. foods, canned foods, dairy products, jams and jellies) (Zeynep and Sifa, 2014). Non-nutritive sweeteners (NSSs) classification includes artificial sweeteners and natural non-caloric sweeteners (Grembecka, Artificial sweeteners used in processed foods are aspartame, 2015) (fig 1). , sucralose, , cyclamate, neotame, , rare sugars, and D-allose (Whitehouse, Boullata Non-nutritive sweeteners (NSSs) have sensible sweetness but and McCauley, 2008). Characteristic attributes of artificial due to low metabolic rate in human body they do not increase sweeteners are shown in Table 1. the calories (Miller and Perez, 2014) (Cheungpasitporn et al., 2014).

IJESC, October 2020 27416 http:// ijesc.org/ Table.1. Characteristic features of artificial sweeteners (Whitehouse, Boullata and McCauley, 2008). General name or Most popular Brand Intensity of Kilo Uses common name names sweetness calories per compared to table gram sugar (kcal/g) Saccharin Sweet’ N Low, 300 0 Soft drinks, beverages, fruit drinks, Sweet Twin powdered dessert mixes, Tabletop sweetener, Jams, , Baked goods, canned fruits

Acesulfame K Sunett, 180-200 0 Tabletop sweeteners (in packets), Sweet One carbonated beverages, desserts which are frozen, , Chewing gum, Dairy products, syrups and sauces

Aspartame NutraSweet, 200 4 Tabletop sweetener (in packets), Natrataste, sugar chewing gums, instant and tea, twin, gelatins, puddings, Soft drinks, Yoghurt, Pharmaceuticals

Neotame Same as common 10000 0 Baked goods, Soft drinks, Chewing name (neotame) gum, Jams, Jellies, Puddings, Processed fruit and fruit

Sucralose 600 0 Tabletop sweetener (in packets), baked foods, Frozen desserts and dairy products, Fruit juices, Chewing gum, gelatins, gelatins

II.TYPES OF ARTIFICIAL SWEETENERS through kidneys (Whitehouse, Boullata and McCauley, 2008). Saccharin is sometimes combined with other artificial Saccharin sweeteners like aspartame because of its slight bitter and Saccharin is an artificial sweetener with zero food energy and no metallic taste (Zeynep and Sifa, 2014). calories. This is the earliest and one of the oldest sugar substitute used for about a century in processed food and beverages Uses industries (Zeynep and Sifa, 2014). Saccharin is 300 times more Saccharin is used in various food products like carbonated soft sweetener than sucrose (Whitehouse, Boullata and McCauley, drinks, tabletop sweeteners, and in few desserts. In hygiene oral 2008). products this sweetener hides the taste of undesirable of other . Apart from its usage as sugar substitute, History saccharin is used as deposition of nickel in electrolyte Saccharin has been identified by Fahlberg and Remsen in the (Periyasamy, 2019). year 1879 at university of John Hopkins (Baltimore). This was accidentally found by Fahlberg during the research on oxidation Toxicity mechanisms of toluene sulfonamide. Saccharin was widely Excess intake or ingestion of saccharin causes severe headache, spread during global wars when the sugar shortage provoked difficulty in breathing, eruptions on skin and diarrhea (Arnold, 1983). Saccharin was banned in the year 1981, because (Whitehouse, Boullata and McCauley, 2008). this caused bladder in rats after giving overdose of saccharin. No clear research has shown the connection between Acesulfame potassium (Ace-k) saccharin intake and risk of cancer in humans (Weihrauch and Acesulfame potassium is used as general sweetener. This is a Diehl, 2004). white crystalline material which is stable up to high temperatures (250 °C). Because of its high stability under high Synthesis and metabolism temperature it is used in many bakery products (Nabors, 1994).

Synthesis of sugar substitute saccharin includes the chemical History oxidation of ortho toluene sulfonamide with reactive chemical Acesulfame potassium has been identified as sugar substitute by agents like permanganate of potash, tetraoxochromic acid, Hoechst (Clauss and Jensen, 1970). During the research on electrochemically to corresponding carboxylic acid. The oxathiazinone oxides this sweetener was discovered by chance. dehydration of ortho isomeric part gives the sweetener saccharin Many other oxathiazinone oxides are sweet in taste but they (Bennett et al. 1992). Saccharin is not metabolized after have less advantageous characteristics (Clauss and Jensen, ingestion, it is excreted from body as it is without any change 1970).

IJESC, October 2020 27417 http:// ijesc.org/ Synthesis and metabolism Uses Early strategies for Ace-k preparation utilized flurosulfonyl Aspartame is commonly applied as artificial sweetener in all isocyanate or chlorosulfonyl with propyne acetone and reacted fields of processed food. with another chemical substances give N-chloro acetoacetamide, this is then cyclized with potassium hydroxide or caustic potash Toxicity to give crystalized Ace-k. Another technique includes treating The individuals who are suffering from a rare phenylketonuria acetoacetamide with any dual equal proportions of sulfuric genetic disorder should avoid intake of aspartame. This caution anhydride. As a result N- sulfoacetoacetamide is formed, the of intake should be clearly mentioned on packaging of processed water is removed by sulfur trioxide to yield oxathiaazinone foods containing aspartame (FDA). The end products (methanol, dioxide. and ) after metabolism of aspartame causes the following health disorders: severe headache, Oxathiaazinone dioxide upon neutralization in presence of improper vision, tumors in brain, sight problems, loss of potassium hydroxide gives the final product Ace-k (Clauss, memory and nausea sensation (Stegink, Filer and Baker, 1977). Schmidt-Rohr and Spiess, 1993). Acesulfame-k is not digested or stored in the human body. This is excreted through urine as Neotame unchanged. Most of the artificial sweeteners are generally Neotame is the recently discovered sweetener which is derived excreted through urine without any modifications (Kier, 1972). from aspartame. Neotame is formed when tertiary butyl group is added to amine free group of aspartic acid. The neotame was Uses accepted as general purpose or tabletop artificial sweetener in Acesulfame-k is mostly used in various fields of sugar the year 2002 except in poultry and by Food and Drug substitutes. Commonly used fields of Ace-k are tabletop Administration (FDA or USFDA) (Whitehouse, Boullata and sweeteners (in packet form), sweet drinks, confectioneries, McCauley, 2008). desserts, dairy products, chewing gums, products and pharmaceutical industries (Periyasamy, 2019). History After the favourable and positive results of aspartame, many Toxicity modifications such as stability to heat, low restrictions and more Methylene chloride which is present in Ace-k is carcinogenic sweetness in aspartame are made to develop a novel sugar which leads to cancer in human body. Excess intake of this may substitute. Hundreds and thousands of compounds were cause severe headache, depression, nausea sensation, mental synthesized. As a result of this research, a noval sweetener with disturbance, liver and renal problems. Ace-k forms all the desirable characters neotame was produced. Neotame got acetoacetamide in human body upon metabolism, which is approval fromFood and Drug Administration (FDA or USFDA) highly toxic and causes tumors in thyroid glands of rats, dogs in the year 2002 (Nofre, 2000). and rabbits. Few studies suggest that only 1% of acetoacetamide is collected in human body for three months (Zeynep and Sifa, Synthesis and metabolism 2014). Neotame is synthesized when tert-butyl group added to amine part of aspartic acid. Neotame is about 60 percent more sweeter Aspartame than aspartame (Nofre, 2000). Neotame is quickly digested by Aspartame is the most discussed sugar substitute which esterase present in the body, this esterase hydrolysis the methyl like sugar. This is highly stable to hot temperatures and has ester group during metabolism. Methanol is formed in little modest solubility in water. This rate of solubility of aspartame is amount which is absorbed by the body. The de-esterified directly proportional temperature (Rencüzoğulları et al., 2004). neotame is eliminated from human body through urine and fecal matter within 72 hours of intake. Neotame is safe sweetener for History those who suffer from phenylketonuria (Nofre, 2000). Aspartame was identified in the year 1965 by chemist G. D. Searle during the series of research on new gastric ulcers drugs. Toxicity Aspartame was accidentally discovered while the synthesis of Excess consumption of neotame causes toxicity in liver. Few tetrapeptide. Food and Drug Administration (FDA or USFDA) other toxic effects of neotame are change in human body weight, accepted aspartame as artificial sweetener in the year 1981. mild headache and loss of appetite (Nofre, 2000). Aspartame is mixed with other sweeteners like saccharin to Sucralose maintain sweetness and other related properties (Butchko and Sucralose is one of the largely consumed sugar substitute. Stargel, 2001). Sucralose is highly stable, safe and even used at higher

temperatures (baked food products). Sucralose is up to 1000 Synthesis and metabolism times more sweeter than sucrose, thrice sweet as aspartame and Aspartame is manufactured by the reaction between acesulfame potassium and sucralose is twice sweet as saccharin phenylalanine methyl ester with aspartic acid or asparaginic (Sims, Roberts, Daniel and Renwick, 2000). acid. This sweetener is metabolized into small amounts of phenylalanine, methanol, aspartic acid. Methanol (carbinol) is History further break down into methyl aldehyde () which Sugar substitutesucralose was unintentionally found by Tate and in turn forms formic acid in the liver of human body. The excess Lyle in the year 1976 while series of research on sucrose. The formaldehyde is excreted through urine through kidney. Little Food and Drug Administration (FDA or USFDA) approved quantity of is produced when aspartame is consumed in sucralose for use in 15 different processed foods (Sims, Roberts, diet (Humphries, Pretorius and Naudé, 2007). Daniel and Renwick, 2000).

IJESC, October 2020 27418 http:// ijesc.org/ Synthesis and metabolism Non therapeutic use Sucralose is synthesized by substituting three hydroxyl groups Aspartame taste same as common sugar which is used as sugar of sucrose with chlorines. This sugar substitute is not substitute in various processed foods. In few beverage and food metabolized and absorbed in human body. Sucralose is excreted industries aspartame is used as a sugar substitute which not only same as it is through fecal matter (Kroger, Meister and Kava, gives sugar taste but also enhances and even intensifies the 2006). (Bellisle and Drewnowski, 2007).

Toxicity HEALTH BENEFITS Toxic effects of sucralose include shrinking of thymus glands, Artificial sweeteners do not increase the sugar levels in blood diarrhea and giddiness (Sims, Roberts, Daniel and Renwick, which is responsible for diabetes. These sugar substitutes have 2000). no calories. As these artificial sweeteners do not increase THERAPEUTIC AND NON THERAPEUTIC USES calories in body they help people to control their weight. They provide good oral health (Whitehouse, Boullata and McCauley, Therapeutic use 2008). Replacement of common table sugar with less or no calorie sugar in food products allows less calories intake into the body TOXIC EFFECTS OF ARTIFICIAL SWEETENERS which in turn helps in reducing weight. High sucrose containing Artificial sweeteners like saccharin, ace-k and aspartame foods may cause dental decay, in order to reduce this problem involves in genetic change, especially in DNA of lymphatic doctors prescribe to use sugar substitutes. People suffering from cells. Few by-products produced from sugar substitutes cause diabetes have fluctuations in blood sugar use of sugar substitutes breakage in DNA strands. These can change the metabolic or artificial sweeteners in diet instead of table sugar allows more properties of human body. Toxic effects of artificial sweeteners stability in blood sugar levels (Bellisle and Drewnowski, 2007). are given in Table 2.

Table.2. Toxic effects of artificial sweeteners (Whitehouse, Boullata and McCauley, 2008). Name of artificial Metabolites Annual Daily Acute problems Chronic problems sweeteners Intake (mg/kg)

Saccharin Ortho 5 Nausea, vomiting, Low birth weight, , sulfamoylbenzoic acid diarrhea hepatotoxicity

Acesulfame- K or ace- Acetoacetamide 15 Headache Thyroid tumors in rats, k clastogenic, high doses cause genotoxicity

Methanol, aspartic 50 Headache, dry Lymphomas and leukemia in case Aspartame acid & phenylalanine mouth, dizziness, of rodents nausea, vomiting, thrombocytopenia, mood swings

Neotame Methanol and de- 2 Headache, Lower birth rate, weight loss, esterified neotame hepatotoxic at high cancer in offspring, doses hepatotoxicity

Sucralose 5 Diarrhea, dizziness, Thymus shrinkage, enlargement stomach pain of cecal in rodents

ADI - Annual Daily Intake

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