Aspartame Research Articles©

In My Aspartame Experiment: Report from a Private Citizen, author Victoria Inness-Brown recounts her controversial 2-1/2 year study of the effects of the artificial sweetener aspartame. Found in packets of NutraSweet or Equal, the sweetener is ingested by an estimated 200 million people and found in over 6,000 consumables, including sodas, candies, coffees, pharmaceuticals, vitamins, and dairy products. Though approved by the FDA, Inness-Brown claims the approval was based on studies cut off before the true effects of the additive could be seen. In addition, human studies use aspartame in capsules, which is not assimilated as fully as its liquid form, thereby minimizing adverse effects. Concerned about the health of family members addicted to diet soda, Inness-Brown raised 108 rats, giving 60 NutraSweet-laced water for 2 ½ years. As her rats on aspartame began manifesting tumors, paralysis, infected and bleeding eyes, and obesity, Inness-Brown made digital videos of the results, culminating in a disturbing visual record of the dangers of the additive. When leaked on the net in 2008, her findings became a hot news topic on popular blogs. Carefully researched, laced with photos and quotes from aspartame sufferers, scientists, and doctors, her book shows that a citizen can go up against a drug conglomerate and provide the public with important new information about a dangerous substance. Not since Rachel Carson’s Silent Spring, has a book held such potential for social change. Her analysis of the environment she provided her rats brings up frightening issues about pesticides, herbicides, genetically modified foods, animal products, water and air quality. She believes that we are the rats of the companies that liberally spread their synthetic chemicals worldwide. No one fully understands the long-term effects-especially the complex interactions from intermixing thousands of toxic chemicals within the plant and animal kingdoms sustaining our planet.

Isabela Finamor, Salvador Pérez, Caroline A. Bressan, Carlos E. Brenner, Sergio Rius-Pérez, Patricia C. Brittes, Gabriele Cheiran, Maria I. Rocha, Marcelo da Veiga, Juan Sastre, and Maria A. Pavanato

Redox Biol. 2017 Apr; 11: 701–707.

Published online 2017 Feb 1. doi: 10.1016/j.redox.2017.01.019

PMCID: PMC5300302 PMID: 28187322

Copyright © 2017 Published by Elsevier B.V.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ​​(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ​​(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway.Keywords: Aspartame, Cysteine, S-adenosylmethionine, N–acetylcysteine

Journal of Neuropathology & Experimental Neurology: November 1996

Oney, John W. MD; Farber, Nuri B.; Spitznagel, Edward; Robins, Lee N.

Abstract

In the past two decades brain tumor rates have risen in several industrialized countries, including the United States. During this time, brain tumor data have been gathered by the National Cancer Institute from catchment areas representing 10% of the United States population. In the present study, we analyzed these data from 197S to 1992 and found that the brain tumor increases in the United States occurred in two distinct phases, an early modest increase that may primarily reflect improved diagnostic technology, and a more recent sustained increase in the incidence and shift toward greater malignancy that must be explained by some other factor(s). Compared to other environmental factors putatively linked to brain tumors, the artificial sweetener aspartame is a promising candidate to explain the recent increase in incidence and degree of malignancy of brain tumors. Evidence potentially implicating aspartame includes an early animal study revealing an exceedingly high incidence of brain tumors in aspartame-fed rats compared to no brain tumors in concurrent controls, the recent finding that the aspartame molecule has mutagenic potential, and the close temporal association (aspartame was introduced into US food and beverage markets several years prior to the sharp increase in brain tumor incidence and malignancy). We conclude that there is need for reassessing the carcinogenic potential of aspartame.

Acta Physiol Hung. 2010 Dec;97(4):401-7. doi: 10.1556/APhysiol.97.2010.4.9.

Polyák E, Gombos K, Hajnal B, Bonyár-Müller K, Szabó S, Gubicskó-Kisbenedek A, Marton K, Ember I.

Environ Health Perspect. 1987 Nov;75:53-7.

Cell Biol Toxicol. 2002;18(1):43-50.

Oyama Y, Sakai H, Arata T, Okano Y, Akaike N, Sakai K, Noda K.

Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Japan. oyama@ias.tokushima-u.ac.jp

Abstract

Aspartame is a widely used artificial sweetener added to many soft beverages and its usage is increasing in health-conscious societies. Upon ingestion, this artificial sweetener produces methanol as a metabolite. In order to examine the possibility of aspartame toxicity, the effects of methanol and its metabolites (formaldehyde and formate) on dissociated rat thymocytes were studied by flow cytometry. While methanol and formate did not affect cell viability in the physiological pH range, formaldehyde at 1-3 mmol/L started to induce cell death. Further increase in formaldehyde concentration produced a dose-dependent decrease in cell viability. Formaldehyde at 1 mmol/L or more greatly reduced cellular content of glutathione, possibly increasing cell vulnerability to oxidative stress. Furthermore, formaldehyde at 3 mmol/L or more significantly increased intracellular concentration of Ca2+ ([Ca2+]i) in a dose-dependent manner. Threshold concentrations of formaldehyde, a metabolite of methanol, that affected the [Ca2+]i and cellular glutathione content were slightly higher than the blood concentrations of methanol previously reported in subjects administered abuse doses of aspartame. It is suggested that aspartame at abuse doses is harmless to humans.

Eur J Clin Nutr. 2006 May;60(5):593-7.

Schulpis KH, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S.

Eur J Clin Nutr. 2006 May;60(5):593-7.

Food Chem Toxicol. 2008 Jun;46(6):2074-9. doi: 10.1016/j.fct.2008.01.050. Epub  2008 Feb 8.

Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.

Abhilash M, Paul MV, Varghese MV, Nair RH.

Neurotox Res. 2012 Apr;21(3):245-55. doi: 10.1007/s12640-011-9264-9. Epub 2011 Aug 6.

Abdel-Salam OM, Salem NA, Hussein JS.

Department of Toxicology and Narcotics, National Research Centre, Tahrir St., Dokki, Cairo, Egypt. omasalam@hotmail.com

Abstract

This study aimed at investigating the effect of the sweetener aspartame on oxidative stress and brain monoamines in normal circumstances and after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS; 100 μg/kg) in mice. Aspartame (0.625-45 mg/kg) was given via subcutaneous route at the time of endotoxin administration. Mice were euthanized 4 h later. Reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid-reactive substances; TBARS), and nitrite concentrations were measured in brain and liver. Tumor necrosis factor-alpha (TNF-α) and glucose were determined in brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver. The administration of only aspartame (22.5 and 45 mg/kg) increased brain TBARS by 17.7-32.8%, decreased GSH by 25.6-31.6%, and increased TNF-α by 16.7-44%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline, and dopamine. Aspartame did not alter liver TBARS, nitrite, GSH, AST, ALT, or ALP. The administration of LPS increased nitrite in brain and liver by 26.8 and 37.1%, respectively; decreased GSH in brain and liver by 21.6 and 31.1%, respectively; increased brain TNF-α by 340.4%, and glucose by 39.9%, and caused marked increase in brain monoamines. LPS increased AST, ALT, and ALP in liver tissue by 84.4, 173.7, and 258.9%, respectively. Aspartame given to LPS-treated mice at 11.25 and 22.5 mg/kg increased brain TBARS by 15.5-16.9%, nitrite by 12.6-20.1%, and mitigated the increase in monoamines. Aspartame did not alter liver TBARS, nitrite, GSH, ALT, AST, or ALP. Thus, the administration of aspartame alone or in the presence of mild systemic inflammatory response increases oxidative stress and inflammation in the brain, but not in the liver.

Drug and Chemical Toxicology, 2013 Apr;39(2):135-40. doi: 10.3109/01480545.2012.658403. Epub  2012 Mar 2.

Abhilash M, Sauganth Paul MV, Varghese MV, Nair RH
School of Biosciences, Mahatma Gandhi University, Kottayam, India

Abstract
The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Journal of Biosciences, 2012 Sep;37(4):679-88.

Iyyaswamy A, Rathinasamy S.

Department of Physiology, University of Madras, Sekkizhar campus, Taramani, Chennai 600 113, India.

This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

Eur Rev Med Pharmacol Sci. 2012 Dec;16(15):2092-101.

Abdel-Salam OM, Salem NA, El-Shamarka ME, Hussein JS, Ahmed NA, El-Nagar ME

Department of Toxicology and Narcotics, National Research Centre, Cairo, Egypt. omasalam@hotmail.com

OBJECTIVE:
The dipeptide aspartame (N-L-alpha-aspartyl-Lphenylalanine, 1-methyl ester; alpha-APM) is one of the most widely used artificial sweeteners. The present study aimed to investigate the effect of repeated administration of aspartame in the working memory version of Morris water maze test, on oxidative stress and brain monoamines in brain of mice.
MATERIALS AND METHODS:
Aspartame (0.625, 1.875 or 5.625 mg/kg) was administered once daily subcutaneously for 2 weeks and mice were examined four times a week for their ability to locate a submerged plate. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide levels (the concentrations of nitrite/nitrate) and glucose were determined in brain.
RESULTS:Only at the highest dose of 5.625 mg/kg, did aspartame significantly impaired water maze performance. The mean time taken to find the escape platform (latency) over 2 weeks was significantly delayed by aspartame 5.625 mg/kg, compared with the saline-treated control group. Significant differences occurred only on the first trial to find the escape platform. Significant increase in brain MDA by 16.5% and nitric oxide by 16.2% and a decrease in GSH by 25.1% and glucose by 22.5% occurred after treatment with aspartame at 1.875 mg/kg. Aspartame administered at 5.625 mg/kg significantly increased brain MDA by 43.8%, nitric oxide by 18.6% and decreased GSH by 32.7% and glucose by 25.8%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline and dopamine.

CONCLUSIONS:
These findings suggest impaired memory performance and increased brain oxidative stress by repeated aspartame administration. The impaired memory performance is likely to involve increased oxidative stress as well as decreased brain glucose availability.

“The American Journal of Clinical Nutrition.” 2010 Sep;92(3):626-33. doi: 10.3945/ajcn.2009.28968. Epub  2010 Jun 30.

Halldorsson TI, Strøm M, Petersen SB, Olsen SF
Centre for Fetal Programming, Statens Serum Institut, Copenhagen, Denmark. lur@ssi.dk

BACKGROUND:

Sugar-sweetened soft drinks have been linked to a number of adverse health outcomes such as high weight gain. Therefore, artificially sweetened soft drinks are often promoted as an alternative. However, the safety of artificial sweeteners has been disputed, and consequences of high intakes of artificial sweeteners for pregnant women have been minimally addressed.

OBJECTIVE:

We examined the association between intakes of sugar-sweetened and artificially sweetened soft drinks and preterm delivery.

DESIGN:

We conducted prospective cohort analyses of 59,334 women from the Danish National Birth Cohort (1996-2002). Soft drink intake was assessed in midpregnancy by using a food-frequency questionnaire. Preterm delivery ( lt 37 wk) was the primary outcome measure. Covariate information was assessed by telephone interviews.

RESULTS:

There was an association between intake of artificially sweetened carbonated and noncarbonated soft drinks and an increased risk of preterm delivery (P for trend: le 0.001, both variables). In comparison with women with no intake of artificially sweetened carbonated soft drinks, the adjusted odds ratio for women who consumed ge 1 serving of artificially sweetened carbonated soft drinks/d was 1.38 (95% CI: 1.15, 1.65). The corresponding odds ratio for women who consumed ge 4 servings of artificially sweetened carbonated soft drinks/d was 1.78 (95% CI: 1.19, 2.66). The association was observed for normal-weight and overweight women. A stronger increase in risk was observed for early preterm and moderately preterm delivery than with late-preterm delivery. No association was observed for sugar-sweetened carbonated soft drinks (P for trend: 0.29) or for sugar-sweetened noncarbonated soft drinks (P for trend: 0.93).

CONCLUSIONS:

Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery. Further studies are needed to reject or confirm these findings.

Journal of Advancement in Medicine, Volume 4, Number 4, Winter 1991

H. J. Roberts, MD

H.J. Roberts MD is Director, Palm Beach Institute for Medical Research.  He is Senior Active Staff, St. Mary’s Hospital and Good Samaritan Hospital, West Palm Beach.  He is author of six texts and was selected the “The Best Doctors in the U.S.”  Address correspondence to H. J. Roberts MD, Palm Beach Institute for MedicalResearch, 6708 Pamela Lane, West Palm Beach, FL 33405 FAX 561-547-8008

ABSTRACT:  There has been a statistically significant increase of common primary malignant brain cancers since 1985, and perhaps as early as 1984, according to the National Cancer Institute SEER data.  This phenomenon occurred within 1-2 years following licensing of the chemical aspartame for beverages in July 1983.  Furthermore, the annual incidence rates of primary brain tumors appear to be increasing.  The SEER data also reveal an increased incidence of primary brain lymphoma in 1982- 1984.  Others have reported a tripling of the incidence of this condition, previously rare.  Again, the licensing of aspartame for “dry” use in July 1981 is relevant.  The significance of these associations is underscored by the high incidence of brain tumors in rats after the experimental administration of aspartame.

Food and Drug Administration (FDA) scientists and a Public Board of Inquiry (PBOI) strongly recommended delay in licensure pending further investigation, including repetition of the animal studies, to clarify this matter.  To the author’s knowledge, these have not been reported.

Aspartame containing products are now being consumed by an estimated 200 million persons in over 4,000 products.  These data, coupled with an unacceptably large number of aspartame-related seizures reported to the FDA and the writer, appear to warrant an “imminent public health hazard” designation for such products.

Clin Exp Rheumatol. 2010 Nov-Dec;28(6 Suppl 63):S131-3. Epub 2010 Dec 22.

Ciappuccini R, Ansemant T, Maillefert JF, Tavernier C, Ornetti P.

Department of Rheumatology, Dijon University Hospital, Burgundy University, Faculty of Medicine, Dijon, France.

Abstract

We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients’ chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient’s diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.

PMID: 21176433