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  1. Chewing gum: hidden harms

    There are a variety of reasons why people chew gums; to freshen their breath, to clean their mouth and even to reduce food cravings, theoretically helping them to avoid eating unhealthy foods. However, while some research has shown that chewing gum can indeed decrease the appetite and the motivation to eat,[1] [2] it has also highlighted the fact that gum chewers' meals can actually end up being less nutritious than those chosen by non-gum-chewers.[3] One study showed, for example, that people who chewed gum were less likely to eat fruit and instead were more motivated to eat junk food.[3] This is likely due to a minty flavor in the gum making fruits and vegetables taste sour or bitter. Regardless of the reason for gum chewing, it can have numerous ill effects on health. This is especially true for people with pre-existing jaw conditions like the painful chronic condition temporomandibular joint disorder (TMJ or TMD).[4] However, even in healthy people, excessive gum chewing can aggravate the cartilage and surrounding joints in the mouth through extra wear and tear.[5] The strain placed on the jaw and surrounding muscles can also increase the incidence of chronic headaches.[6] Chewing gum also causes you to swallow excess air,[7] which can contribute to abdominal pain and bloating seen with irritable bowel syndrome (IBS).[8] Furthermore, chewing gum sends physical signals to the body indicating that food is about to be ingested, resulting in increased production of stomach acid in preparation.[9] Excess stomach acid can have a wide range of negative effects on the digestive system, including ulceration.[10]  Sugar free chewing gums often contain artificial sweeteners, such as aspartame or sucralose. Aspartame has been linked to numerous deleterious effects on health, including headaches, insomnia and seizures,[11] as well as changes in metabolism and weight gain.[12] Sucralose consumption can also have numerous ill effects. Animal studies showed that 12 weeks sucralose administration reduced beneficial gut bacteria, increased fecal pH, and altered the expression of enzymes involved in drug metabolism.[13] So next time you chew gum, remember that you may be doing more to your body than just freshening your breath. Gum chewing has been linked to effects on metabolism and appetite, as well as potentially causing harm to the jaw and digestive system. Chewing gum should therefore ideally be kept to a minimum where possible.   [1] Park, E, et al. (2016) Short-term effects of chewing gum on satiety and afternoon snack intake in healthy weight and obese women. Physiol Behav. 159. 64-71. [2] Hetherington, MM & Boyland, E. (2007) Short-term effects of chewing gum on snack intake and appetite. Appetite. 48(3). 397-401. [3] Swoboda, C & Temple, JL. (2013) Acute and chronic effects of gum chewing on food reinforcement and energy intake. Eating Behaviours. 14(2). 149-56. [4] Haggman-Henrikson, B, et al. (2004) Endurance during chewing in whiplash-associated disorders and TMD. J Dent Res. 82(12). 946-50 [5] Blasberg, B & Greenberg, MS. (2003) Temporomandibular disorders In Burket’s Oral Medicine. PMPH, USA [6] Watemberg, N, et al. (2014) The influence of excessive chewing gum use on headache frequency and severity among adolescents. Pediatr Neurol. 50(1). 69-72. [7] Silva, AC, et al. (2015) Effect of gum chewing on air swallowing, saliva swallowing and belching. Arg Gastroenterol. 52(3). 190-4. [8] Friedman, G. (1991) Diet and the irritable bowel syndrome. Gastroenterol Clin North Am. 20(2). 313-24. [9] Helman, CA. (1988( Chewing gum is as effective as food in stimulating cephalic phase gastric secretion. Am J Gastroenterol. 83(6). 640-2/ [10] Hunt, RH, et al. The stomach in health and disease. Gut. 64(10). 1650-1668. [11] Humphries, P, et al. (2008) Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 62. 451-62.  [12] Feijo Fde, M, et al. (2013) .Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels. Appetite. 60(1). 203-7. [13] 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. 71(21). 1415-29.
  2. I have found an alarming scientific article on aspartame It looks that it is a really dangerous substance, perhaps even more than thought by most. The article concluded that doses much smaller than recommended daily intake influence people's neurobehavioral health, i.e. participants who consumed aspartame were prone to depression and other mental ailments such as irritation.  I would like scientists to look for similar researches and comprehensively write on aspartame effects on our brain in layman terms
  3. Aspartame is a widely used artificial sweetener that has been associated with various health concerns, including seizures,[1] insomnia and migraines in children, adolescent and adults.[2] [3] Indeed studies suggest that aspartame can actually be a common trigger for migraines, especially when consumption is prolonged.  Aspartame is composed of phenylalanine, aspartic acid and methanol. Phenylalanine is an important regulator of neurotransmission, whereas aspartic acid actually acts as a neurotransmitter in the central nervous system.[4] When ingested and then digested, aspartame is broken down in the gut wall into these aforementioned constituents.[5] [6] Methanol, which constitutes 10% of aspartame and can also be produced by conversion from aspartic acid, is oxidized in the body to form formic acid, formaldehyde[5] and numerous other carcinogenic and toxic derivatives.[3] Formaldehyde, a carcinogen,[7]  is known to bind with nucleic acids and proteins, forming adducts that are difficult to remove via normal metabolic pathways and thus can accumulate within the body.[8] The consumption of aspartame has been linked to various neurological and behavioural reactions.[9] One study showed, shockingly, that healthy adults who were given just half of the the maximum acceptable daily intake level of 40-50 mg/kg body weight/day for just 8 days had a more irritable mood, exhibited more signs of depression and performed worse on orientation tests than those given a low aspartame diet.[9] Although some studies have found that aspartame did not cause more headaches than placebo, other evidence strongly suggests that it may be a trigger in people who consume moderate to high amounts (900 to 3000 mg/day) over a prolonged period of time.[3] Aspartame’s headache-causing properties are potentially a result of regional increases in neurotransmitters in the brain, including norepinephrine, epinephrine and dopamine.[11] It has also been shown that aspartame disrupts protein structure and metabolism, amino acid metabolism, the integrity of nucleic acids, nervous system function and hormone balances.[12] Aspartame breakdown products such as phenylalanine, aspartic acid and phenylalanine methyl ester cause neurons to fire excessively, which can indirectly cause a high rate of brain cell activity.[13] The link between aspartame ingestion and headaches, on top of all the other toxic side effects of aspartame, mean that its consumption should be avoided, particularly by those susceptible to headaches and migraines. This is especially important, as adverse effects have been seen in doses as low as half the currently recognised “safe” limit. Perhaps, therefore, it is not just our consumption that needs to change, but also the regulations that claim to be protecting us.     [1] Maher, TJ, Wurtman, RJ. (1987) Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspect. 75. 53-7. [2] Millichap, JG, Yee, MM. (2003) The diet factor in pediatric and adolescent migraine. Pediatr Neurol. 28(1). 9-15. [3] Sun-Edelstein, C, Mauksop, A. (2009) Foods and supplements in the management of migraine headaches. Clin J Pain. 25(5). 446-52. [4] Humphries, P, Pretorius, E, Naudé, H. (2008) Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 62(4). 451-62. [5] Jacob, SE, Stechschulte, S. (2008) Formaldehyde, aspartame, and migraines: a possible connection. Dermatitis. 19(3). E10-1. [6] Oppermann, JA, Muldoon, E, Ranney, RE. (1973) Metabolism of aspartame in monkeys. Nutrition. 103. 1454-9. [7] Swenburg, JA, Moeller, BC, Lu, K, Rager, JE, Fry, R, Starr, TB. (2013) Formaldehyde Carcinogenicity Research: 30 Years and Counting for Mode of Action, Epidemiology, and Cancer Risk Assessment. Toxicol Pathol. 41(2). 181-9. [8] Trocho, C, Pardo, R, Rafecas, I, Virgili, J, Remesar, X, Fernández-López, JA, Alemany, M. (1998) Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci. 63(5). 337-49. [9] Lindseth, GN, Coolahan, SE, Petros,TV, Lindseth, PD. (2014) Neurobehavioural effects of aspartame consumption. Res Nurs Health. 37(3). 185-93. [10] Maher, TJ, Wurtman, RJ. (1987) Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspect. 75. 53-7. [11] Fernstrom, JD. (1988) Effects of Aspartame Ingestion on Large Neutral Amino Acids and Monoamine Neurotransmitters in the Central Nervous System In Effects of Aspartame Ingestion on Large Neutral Amino Acids and Monoamine Neurotransmitters in the Central Nervous System. Springer, US. [12] Filer, LJ, Stegink, LD. (1988) Effects of Aspartame on Plasma Phenylalanine Concentration in Humans In Effects of Aspartame Ingestion on Large Neutral Amino Acids and Monoamine Neurotransmitters in the Central Nervous System. Springer, US. [13] Fountain, SB, Hennes, SK, Teyler, TJ. (1988) Aspartame exposure and in vitro hippocampal slice excitability and plasticity. Fundament Appl Toxicol. 11(2). 221-8.  
  4. Aspartame: a daily toxin

    It was previously approved for use in 1974, but its approval was put on hold due to objections filed by neuroscientist[1] Aspartame is a compound consisting of 3 chemicals: methanol, and the amino acids aspartic acid and phenylalanine. It is a non-nutritional food additive (European Food Safety Authority [EFSA] additive code E951), which means that it has no nutritional value and is regulated by EFSA. Aspartame was approved by the Federal Drug Agency (FDA) for use in dry goods in 1981 and in carbonated beverages in 1983.Dr John W. Olney (who found aspartame caused holes in the brains of mice) and consumer attorney James Turner (who believed aspartame could cause brain damage), and investigations into the research practices of G.D. Searle, who did not inform the FDA of one study in which an infant monkey died after 300 days’ consumption of milk sweetened with aspartame.[1] [2] Following aspartame’s approval in the US, it quickly also gained approval in the UK in 1982, after a review of its safety by the UK's Committee on Toxicity, Consumer Products and the Environment.[3] This then led to European-wide approval of aspartame with the universal adoption of the EU Sweetener Regulations (94/35/EC) in 1994.[4] Today aspartame is widely used as a non-nutritive sweetener, as a replacement for sugar. As excessive sugar is linked to numerous health conditions including diabetes, obesity and metabolic syndrome, substituting with an artificial sweetener would seem to be beneficial for health. However this may not necessarily be the case. Aspartic acid (also known as aspartate), one of the components of aspartame, acts as neurotransmitter in the brain, facilitating the transmission of information from neuron to neuron. The excess of aspartate in the blood shortly after ingesting aspartame could therefore lead to a high level of these neurotransmitters in certain areas of the brain.[5] This surplus of neurotransmitters in the brain can kill neurons by allowing an influx of too much calcium into the cells.[6] This influx triggers the production of excessive amounts of free radicals, which destroy the cells. These chemicals are known as “excitotoxins” because they “excite” or stimulate the cell to death.[7] Disorders, such as attention deficit hyperactivity disorder (ADHD). The behaviourFurthermore, exposure to non-nutritional food additives during the critical developmental window during childhood has been implicated in the induction and severity of blood brain barrier (BBB), which protects the brain from excess glutamate (a breakdown product of aspartate), aspartate and other toxins, is not completely developed until after birth.[8] The brains of unborn and young children are therefore not fully protected from toxin exposure, such as that caused by excessive aspartame ingestion. In adults the efficacy of the BBB can also be reduced as a consequence of chronic and acute conditions.[9] However, even when intact, the BBB permits seepage of excess aspartate and glutamate into the brain, which slowly destroys neurons through excitotoxicity as described above. [10] Whilst the quantities of non-nutritional food additives in single servings may be considered “safe”, the cumulative effect of several ingested together is, at the very least, questionable.[11] Aspartame is known to have the potential to cause adverse effects, which can be serious, including seizures.[12] The severity of these reactions can be the result of unnoticed cell death within the brain, which is highly plastic in its ability to cope with widespread cell death.[13] In the light of what evidence is available, it is therefore perhaps advisable to limit aspartame intake.   [1] Nill, A (2000) The History of Aspartame. Retrieved October 2016 from,,_Ashley_-_The_History_of_Aspartame.pdf?sequence=3 [2] FDA (2003) Docket #02P-0317 Recall aspartame as a neurotoxic drug: file #7: aspartame history. Retrieved April 2016 from, [3] FSA (2016) Aspartame. Retrieved April 2016 from, [4] Ashurst, PR. (2008) Chemistry and Technology of Soft Drinks and Fruit Juices. Retrieved April 2016 from, [5] Kudo, Y, Ogura, A. (1986) Glutamate-induced increase in intracellular Ca2+ concentration in isolated hippocampal neurones. Br J Pharmacol. 89(1). 191-8. [6] Arundine, M, Tymianski, M. (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium. 34(4-5). 325-37. [7] Olney, JW. (1994) Excitotoxins in foods. Neurotoxicology. 15(3). 535-44. [8] Marc, T. (2013) Brain development and the immune system: an introduction to inflammatory and infectious diseases of the child’s brain. Handb Clin Neurol. 112. 1087-9. [9] Yang, Y, Rosenberg, GA. (2011) Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke. 42(11). 3323-8. [10] Choi, DW, Koh, JY, Peters, S. (1988) Pharmacology of glutamate neurotoxicity in cortical cell culture attenuation by NMDA antagonists. J Neurosci. 8(1). 185-96. [11] Lau, K, McLean, WG, Williams, DP, Howard, CV. (2006) Synergistic interactions between commonly used food additives in a developmental neurotoxicity test. Toxicol Sci. 90(1). 178-87. [12] Humphries, P, Pretorius, E, Naude, H. (2008) Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 62(4). 451-62. [13] Wieloch, T, Nikolich, K. (2006) Mechanisms of neural plasticity following brain injury. Curr Opin Neurobiol. 16(3). 258-64.
  5. Logic would suggest that consuming fewer calories should result in weight loss, or at the very least, prevent weight gain. However, in the case of artificial sweeteners, which are lower in calories than sugar,  there is a paradox in that it has been shown that they can actually cause weight gain. Therefore, diet drinks are potentially far from the ‘healthier’ calorie-free alternative to regular drinks that they claim to be. As the artificial sweeteners present in diet drinks are now thought to contribute to the development of obesity,[1] they could in fact actually be quite unhealthy. Artificial sweeteners such as sucralose and aspartame have zero calories yet are intensely ‘sweet’ tasting, but the brain is not as easily fooled as the tongue. Artificial sweeteners provide less actual ‘sweetness’ satisfaction, and furthermore reduce the satisfaction obtained when ‘real’ sugar is consumed.[2] This can actually lead to increased carbohydrate cravings, boosting the inclination to overindulge.[2] [3] The first hints at the potential risks of artificial sweeteners arose over two decades ago when studies began revealing that they can stimulate the appetite,[4] with further investigations linking them to increased carbohydrate cravings,[3] the stimulation of fat storage[5] and weight gain.[1] One recent study that followed 474 diet soda drinkers for nearly 10 years, found that they had a staggering 400% greater increase in waist size during the 10 year study period than those who did not drink diet sodas.[6] This increased waist size is not just an aesthetic issue, it is a powerful indicator of the accumulation of visceral fat. This is a dangerous type of fat that gathers around the internal organs, and is strongly linked with type 2 diabetes and heart disease.[7] [8] In fact waist size is now considered a more powerful predictor of cardiovascular risks than body mass index (BMI).[9] However increased body weight is not the only controversial potential side effect of diet drinks. Early studies showed that some artificial sweeteners caused bladder cancer in laboratory animals, [10] although further studies failed to provide clear evidence of an association with cancer in humans, leaving the results inconclusive.[11] Reports also suggest an association between the consumption of aspartame, a widely used artificial sweetener, and neurological and behavioural reactions.[12] Aspartame has been shown to have the potential to induce serious adverse reactions, including seizures.[13]  So if you’re trying to lose weight, so-called ‘diet’ drinks may not be the healthy alternative that they claim to be. They have the potential for major metabolic, cardiovascular and neurological side effects and can actually contribute to weight gain. That being said, sugary drinks are also potentially damaging to health, so care should also be taken with their consumption. Why not opt for safe and simple water, the benefits of which are well known.   [1] Pepino, MY. (2015) Metabolic effects of non-nutritive sweeteners. Physiol Behav. 152(Pt B). 450-5. [2] Rudenga, KJ, Small. DM. (2012) Amygdala response to sucrose consumption is inversely related to artificial sweetener use. Appetite. 58(2). 504-7. [3] Yang, Q. (2010) Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings. Yale J Biol Med. 83(2). 101-8. [4] Rogers, PJ, Blundell, JE. (1989) Separating the actions of sweetness and calories: Effects of saccharin and carbohydrates on hunger and food intake in human subjects. Physiol Behav. 45(6). 1093-9. [5] Maersk, M, Belza, A, Stødkilde-Jørgensen, H, Ringgaard, S, Chabanova, E, Thomsen, H, Pedersen, SB, Astrup, A, Richelsen, B. (2012) Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fatdepot: a 6-mo randomized intervention study. Am J Clin Nutr. 95(2). 283-9. [6] Fowler, RP, Williams, K, Hazuda, HP. (2015) Diet soda intake is associated with long-term increases in waist circumference in a biethnic cohort of older adults: the San Antonio Longitudinal Study of Aging. J Am Geriatr Soc. 63(4). 708-15 [7] Abraham, TM, Pedley, A, Massaro, JM, Hoffmann, U, Fox, CS. (2015) Association between visceral and subcutaneous adipose depots and incident cardiovascular disease risk factors. Circulation. 132(17). 1639-47.  [8] Han, TS, Lean, ME. (2016) A clinical perspective of obesity, metabolic syndrome and cardiovascular disease. JRSM Cardiovasc Dis. [epub ahead of print] doi: 10.1177/2048004016633371. [9] Bastien, M, Poirier, P, Lemieux, I,  Després, JP. (2014) Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog Cardiovasc Dis. 56(4). 369-81. [10] Takayama, S, Sieber, SM, Adamson, RH, Thorgeirsson, UP, Dalgard, DW, Arnold, LL, Cano, M, Eklund, S, Cohen, SM. (1998) Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. J Natl Cancer Inst. 90(1). 19-25. [11] Kessler, II, Clark, P. (1978) Saccharin, cyclamate and human bladder cancer. No evidence of an association. JAMA. 240(4). 349-55.  [12] Lindseth, GN, Coolahan, SE, Petros,TV, Lindseth, PD. (2014) Neurobehavioural effects of aspartame consumption. Res Nurs Health. 37(3). 185-93. [13] Maher, TJ, Wurtman, RJ. (1987) Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspect. 75. 53-7.
  6. 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,   [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, [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, [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.