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  1. What is healthy artificial sweetener “Artificial sweetener” is term used for any sugar substitute used to replace sucrose (table sugar). These sugar substitutes may be synthetically manufactured or derived from chemicals that occur naturally in sources including herbs and sucrose itself. They differ from sucrose in two main respects; firstly they are known as “intense” sugars, as they are many times sweeter than traditional sugar and secondly, their calorific value is much lower, sometimes reaching zero. The fact that the quantity required for the same level of sweetness is a fraction of that of regular sugar makes sweeteners an attractive sugar substitute, both in terms of the potential for weight loss and their use by diabetics, who normally have to avoid sugar.[1] Therefore, sweeteners are widely used in processed foods including baked goods, soft drinks, canned food and dairy products, as well as being available for home use, and in cooking.    Some artificial sweeteners are considered as ‘food additives’, and are officially as such regulated by government bodies such as the European Food Safety Authority (EFSA) or the Food and Drug Administration (FDA) in the US, requiring review and approval before use. The EFSA and FDA declare a substance “generally recognised as safe” if there are sufficient scientific safety data available. However in certain cases substances may be declared safe on the basis of a long history of common use in food. Upon approval, the food safety agency establishes an acceptable daily intake (ADI) for each substance which is intended to be a lot less than the smallest amount that may result in health concerns.[2] Scrutiny of artificial sweeteners has been intense for decades. Critics believe that they cause a variety of health problems, including cancer in the case of one sweetener, saccharin, EFSA approved food additive by code E954. These concerns are mainly derived from studies performed in the 1970s which linked saccharin to bladder cancer in laboratory rats.[3] These data resulted in saccharin carrying a health warning for some time.[4] However since these initial studies, The National Cancer Institute and other health agencies have been unable to find sound scientific evidence of a link between this approved artificial sweetener and cancer,[5] [6] and the warning label on saccharin was therefore subsequently lifted in 2001.[7] Sucralose, EFSA approved food additive by code E955, an artificial sweetener marketed as Splenda®, is found in a wide variety of low calorie foods including ‘diet’ carbonated drinks, chewing gum, table top sweeteners, breakfast cereals and salad dressings. As it is intensely sweet (up to 650 times sweeter than sugar) sucralose is often mixed with other, less sweet ingredients that are not calorie free, such as dextrose or maltodextrin, to dilute its sweetness. Splenda® gained FDA approval as a table-top sweetener in 1998 and for more general use in 1999.[8] However recent studies in rats indicated that administration of Splenda®  for 12 weeks exerted numerous adverse effects, including a reduction in beneficial faecal microflora, increased faecal pH and enhanced expression of key components of the pre-systemic detoxification system involved in first class drug metabolism, known to limit the bioavailability of orally administered drugs.[9] [10]   Another artificial sweetener, aspartame, EFSA approved food additive by code E951, has also been shown to have the potential to be harmful to health. Excessive intake can lead to cell death within the brain, caused by a buildup of its key components such as aspartate in the brain, which can lead to a process called excitotoxicity.[11] Indeed, aspartame has been shown to have numerous adverse effects, a large proportion of which are serious, including seizures and death.[12] It has also been suggested that artificial sweeteners may actually increase the risk of becoming obese, and may be associated with type 2 diabetes when consumed regularly over a long period. Indeed studies have shown that people who drink 1 or more ‘diet’ drinks per day are 67% more likely to develop diabetes than those who don’t drink any.[13]  It is thought that effects such as these may be due to increased carbohydrate cravings and an inclination to overindulge.[14] [15] This is because, despite the fact that artificial sweeteners trigger more communication with the brain’s pleasure centre than sugar, artificial sweeteners provide less actual ‘sweetness’ satisfaction.[14] There are numerous adverse health effects associated with artificial sweetener intake, and seemingly minimal benefits. It may therefore be wise to avoid them and to decrease calorie intake by opting for healthier, natural alternatives.   [1] Qurrat-ul-Ain. & Khan, SA. (2015) Artificial sweeteners: safe or unsafe? J Pak Med Assoc. 65(2). 225-7. [2] EFSA (date unknown) Food Additives. Retrieved October 2016 from, https://www.efsa.europa.eu/en/topics/topic/additives   [3] Price, JM. et al. (1970) Bladder tumors in rats fed cyclohexylamin or high doses of a mixture of cyclamate and saccharin. Science. 167(3921). 1131-2. [4] NIH (2009) Artificial sweeteners and cancer. Retrieved October 2016 from, https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet [5] Mishra, A. et al. (2015) Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants. Int J Clin Pract. 69(12). 1418-26. [6] Kamenickova, A. et al. (2013) Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells. Toxicology in Vitro. 27(8). 2283-88. [7] DUJS (2008) Artificial Sweeteners: The Truth About Diet Soda. Retrieved October 2016 from, http://dujs.dartmouth.edu/2008/04/artificial-sweeteners-the-truths-and-lies-behind-diet-soda/#.WANcWOArK00 [8] Stipanuk MH. & Caudill MA. (2012) Biochemical, Physiological and Molecular Aspects of Human Nutrition. 3rd edtn. Saunders, United States [9] Abou-Donia, MB. et al. (2008) Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 71(21). 1415-29. [10] Schiffman, SS. & Rother, KI. (2013) Sucralose, a synthetic organochlorine sweetener: overview of biological issues. J Toxicol Environ Health B Crit Rev. 16(7). 399-451. [11] Arundine, M. & Tymianski, M. (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium. 34(4-5). 325-37. [12] Humphries, P. et al. (2008) Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 62(4). 451-62. [13] Nettleton JA, et al. (2009) Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 32(4). 688-94. [14] Rudenga, KJ. & Small. DM. (2012) Amygdala response to sucrose consumption is inversely related to artificial sweetener use. Appetite. 58(2). 504-7. [15] Yang, Q. (2010) Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings. Yale J Biol Med. 83(2). 101-8.