PUBLISHED PEER-REVIEWED RESEARCH - ASPARTAME ARTIFICIAL SWEETENERS (NutraSweet/Equal/Canderel, etc.)

Dear Reader: Most of the Studies Referenced on this page, prior to 1999, were taken partially from our Toxicology sourcebook: Deadly Deception Story of Aspartame-Shocking Exposé of World's Most Controversial Sweetener. We wish to thank Dr. Joseph Mercola for organizing these studies into List Form and publishing the List on his extensive website. Many of the Researchers whose names appear as authors of these studies, are friends, acquaintances of mine, who have supported our Aspartame Awareness Campaign with their findings and, in some cases, also their friendship. Having provided Sworn Testimony at the Senate Hearings on Aspartame Safety, Nov. 3, 1987, and having qualified in Sworn Testimony in Court, as an Expert Medical (Aspartame) Witness, our involvement predates virtually all found published on anti-aspartame websites on the Internet. Rarely is 'attribution' given by these sites to the organization (Aspartame Consumer Safety Network) that started it all. My ACSN Co-Founder, James Turner Esq. and I did much of the investigative footwork that produced the indicting evidence of Aspartame's harm that is so freely re-published by others today … often claiming the work as their own. 

For the past three decades, I have dedicated my life to educating others the whole Truth about the Aspartame Story - using my own personal, limited funds and nothing from outside sources. I sell nothing on the Internet or elsewhere, nor do I collect a percentage of the profits for any of the good products I recommend, such as the sugarfree gum found in Health Food Stores, for example. I say this, only to clarify my involvement as one of a passionate volunteer who wants to see wrongs made right and our children and everyone else to not fall prey to a deadly toxin in the world's food supply. -- 

Respectfully,

Hon. Mary Nash Stoddard/author Deadly Deception Story of Aspartame - World's Most Controversial Sweetener (Odenwald Press 1998)

Founder: Aspartame Consumer Safety Network and Pilot Hotline (1987-present)

(Sworn Officer of the Court for the State of Texas, serving a full Term: 1977-1983 Dallas, TX)

https://twitter.com/marystod

http://marystod.blogspot.com/

www.aspartamesafety.com

Health Problem: Brain damage/Cognitive skills disruption/Retardation/Neurochemical changes in the brain/Behavioral and Mood Changes/Problems

1. Year Published: 1970
   Full Reference: Brain Damage in Infant Mice Following Oral Intake of Glutamate, Aspartate, or Cysteine; Nature 1970;227-609-610
   Funded By: Washington University
   Conclusion/Findings: Irreversible degenerative changes and acute neuronal necrosis
   Hyperlink to Study http://www.nature.com/nature/journal/v227/n5258/pdf/227609b0.pdf
2. Year Published: 2008
   Full Reference: Direct and Indirect Cellular Effects of Aspartame on the Brain. European Journal of Clinical Nutrition (2008) 62, 451-462; P. Humphries, E. Pretorius, and H. Naude
   Funded By: Not known
   Conclusion/Findings: Excessive aspartame ingestion might cause certain mental disorders, as well as compromised learning and emotional functioning
   Hyperlink to Study: http://www.newmediaexplorer.org/sepp/aspartamebrain.pdf
3. Year Published: 2007
   Full Reference: Life-Span Exposure to Low Doses of Aspartame Beginning During Prenatal Life Increases Cancer Effects in Rats, Morando Soffritti, Fiorella Belpoggi, Eva Tibaldi, Davide Degli Esposti, Michelina Lauriola; Environmental Health Perspectives, 115(9) Sep 2007; 115:1293-1297. doi:10.1289/ehp.10271. 
   Funded By: Not known
   Conclusion/Findings: Carcinogenicity proven a second time; with effects increased when exposure to aspartame begins during fetal life.
   Hyperlink to Study: http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info:doi/10.1289/ehp.10271
4. Year Published: 1984
   Full Reference: Effects of Aspartame and Glucose on Rat Brain Amino Acids and Serotonin. Yokogoshi H, Roberst CH, Caballero B, Wurtman RJ. American Journal of clinical Nutrition. 1984 July, 40(1):1-7
   Funded By: MIT
   Conclusion/Findings: High aspartame doses can generate major neurochemical changes in rats, especially when consumed along with carbohydrate-containing foods
   Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/6204522
5. Year Published: 1984
   Full Reference: Revelance of Animal Studies to Human Safety. Olney, JW. Neurobehavioral Toxicology and Teratology. 1984; 6:455-462
   Funded By: MIT
   Conclusion/Findings: Excitotoxins, as used in foods today, may produce blood elevations high enough to cause damage to the nervous system of young children, damage which is not detectable at the time of occurrence but which may give rise to subtle disturbances in neuroendocrine function in adolescence and/or adulthood.
   Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/6152304
6. Year Published: 1996
   Full Reference: Increasing Brain Tumor Rates: Is There a Link to Aspartame? Olney JW, Farber NB, Spitznagel E, Robins LN. Journal of Neuropatholgy & Experimental Neurology. 1996 Nov; 55(11):1115-23
   Funded By: NIH
   Conclusion/Findings: Brain tumor incidence in the US implicates the introduction of aspartame into the American diet.
   Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/8939194
7. Year Published: 2000
   Full Reference: Glutamate and Aspartate Impair Memory Retention and Damage Hypothalamic Neurons in Adult Mice. Cheol Hyoung Park, Se Hoon Coi, et al. Toxicology Letters, Vol. 115, Issue 2, May 19, 2000, pp. 117-125
   Funded By: Not known
   Conclusion/Findings: Found that aspartate shortens the memory response, impairs memory retention and damages hypothalamic neurons in mice
   Hyperlink to Study: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-408BJC1-4&_user=10&_coverDate=05%2F19%2F2000&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view
   =c&_searchStrId=1456058577&
   _rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=395a2fc9d4ef0ffceeea475146341607
   &searchtype=a
8. Year Published: 2002
   Full Reference: Effect of Aspartame on N-Methyl-D Asparate Sensitive L-(311) Glutamate Binding Sites in Rat Brain Synpatic Membranes, AV Glushakov, DM Dennis, et al. Molecular Psychiatry, 2002, Vol. 7, No. 4, pp. 359-367.
   Funded By: University of Florida
   Conclusion/Findings: Shows that aspartate has a role in causing mental retardation, but the mechanism by which it does that is still unknown.
   Hyperlink to Study: http://www.nature.com/mp/journal/v7/n4/full/4000976a.html
9. Year Published: 2006
   Full Reference: The Effect of Aspartame Metabolites on Human Erythrocyte Membrane Acetylcholinesterase Activity. Stylianos Tsakiris, Aglaia Giannoulia-Karantana, et al., Pharmacological Research, Volv. 53, Issue 1, Jan. 2006. pp. 1-5.
   Funded By: Not known
   Conclusion/Findings: Found that high concentrations of aspartame can cause neurological symptoms, including memory and learning problems.
   Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/16129618
10. Year Published: 2008
    Full Reference: Direct and Indirect Cellular Effects of Aspartame on the Brain, P Humphries, E Pretorius and H Naude, European Journal of Clinical Nutrition , 2008, 62, 451-462
    Funded By: Not known
    Conclusion/Findings: Asserts that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders (DSM-IV-TR 2000) and also in compromised learning and emotional functioning.
    Hyperlink to Study: http://www.nature.com/ejcn/journal/v62/n4/abs/1602866a.html
11. Year Published: 1986
    Full Reference: Evaluation of Reactions to Food Additives: The Aspartame Experience. MK Bradstock, MK Serdula, JS Marks, RJ Barnard, Nt Crane, PL Remington and FL Trowbridge. The American Journal of Clinical Nutrition. Vol. 43, pp. 464-469, 1986
    Funded By: Not known
    Conclusion/Findings: Identified some case reports in which the symptoms may be attributable to aspartame in commonly-consumed amounts. Headache, mood alterations (anxiety, agitation, irritability, or depression), insomnia, dizziness, and fatigue were the most frequently reported symptoms, with one case of a child in a double-blind test who became hyperactive after consuming products with aspartame.
    Hyperlink to Study: http://www.ajcn.org/cgi/reprint/43/3/464 and http://www.ajcn.org/cgi/content/abstract/43/3/464
12. Year Published: 1990
    Full Reference: Aspartame: Clinical Update, Potenza DP, el-Mallakh RS, Connecticut Medicine, 1990 Apr;54(4):235-6.
    Funded By: Not known
    Conclusion/Findings: Raises concern that so many reports of headaches, seizures, blindness, and cognitive and behavioral changes with long-term, high-dose aspartame have been reported that health officials need to be concerned.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/2667892
13. Year Published: 1993
    Full Reference: Adverse Reactions to Aspartame: Double-Blind Challenge in Patients from a Vulnerable Population. Ralph G. Walton, Robert Hudak, Ruth J. Green-Waite. Psychiatry. July 1, 1993. Vol. 34, Issue 1, pp. 13-17.
    Funded By: Dept. of Psychiatry Northeastern Ohio,Universities  College of Medicine and University Hospital of Cleveland
    Conclusion/Findings: Found that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged. In the clinical study, the project was halted by the Institutional Review Board after a total of 13 individuals had completed the study because of the severity of reactions within the group of patients with a history of depression 
    Hyperlink to Study: http://www.biologicalpsychiatryjournal.com/article/0006-3223%2893%2990251-8/abstract
14. Year Published: 1986
    Full Reference: Seizure and Mania After High Intake of Aspartame
    Funded By: Jamestown General Hospital, Jamestown, New York
    Conclusion/Findings: Case report of a woman who drank in excessive of 1 gallon per day of iced tea sweetened with aspartame, resulting in manic episode and seizure that led to hospitalization.
    Hyperlink to Study: http://psy.psychiatryonline.org/cgi/pdf_extract/27/3/218
15. Year Published: 1991
    Full Reference: Effect of Aspartame and Protein, Administered in Phenylalanine-Equivalent Doses, on Plasma Neutral Amino Acids, Aspartate, Insulin and Glucose in Man, Svend E. Moller; Pharmacology & Toxicology, Vol. 68, Issue 5, pp. 408-412.
    Funded By: Clinical Research Laboratory, Denmark
    Conclusion/Findings: The study showed that the intake of aspartame in a not unrealistically high dose produced a marked and persistent increase of the availability of Phe to the brain, which was not observed after protein intake. The study indicated, furthermore, that Phe was cleared faster from the plasma after consumption of protein compared with aspartame.
    Hyperlink to Study: http://www3.interscience.wiley.com/journal/122214234/abstract
16. Year Published: 1994
    Full Reference: Effects of Diets High in Sucrose or Aspartame on the Behavior and Cognitive Performance of Children. Mark L. Wolraich, Scott D. Lingren, et al. New England Journal of Medicine, Feb. 3, 1994; pp. 330:301-307
    Funded By: Not known
    Conclusion/Findings: Reported that it is possible that there are some children who respond adversely to sugar or aspartame.
    Hyperlink to Study: http://www.nejm.org/doi/full/10.1056/NEJM199402033300501#articleResults
17. Year Published: 1985
    Full Reference: Loss of Intellectual Function in Children with Phenylketonuria After Relaxation of Dietary Phenylalanine Restriction, Margretta R. Seashore, Estelle Friedman, Robert A. Novelly P, Vijaya Bapat MD. Pediatrics vol. 75, No. 2, Feb. 1985, pp. 226-232
    Funded By: Not known
    Conclusion/Findings: Shows decrease in intellectual function in children with PKU who have phenylalnine introduced into their diets.
    Hyperlink to Study: http://pediatrics.aappublications.org/cgi/content/abstract/75/2/226
18. Year Published: 1987
    Full Reference: Aspartame Effects on Brain Serotonin, RI Wurtman, Letter in American Journal of Clinical Nutrition, 1987 April; 45(4):799-803
    Funded By: MIT
    Conclusion/Findings: Argues that using rodents to disprove aspartame's harm to humans is not relevant, and that it reacts more negatively in humans than in mice
    Hyperlink to Study: http://www.ajcn.org/cgi/reprint/45/4/799.pdf
19. Year Published: 1986
    Full Reference: Acute Effects of Oral or Parenteral Aspartame on Catecholamine Metabolism in Various Regions of Rat Brain, Hidehiko Yokogoshi and Richard J. Wurtman, The Journal of Nutrition, November 1986
    Funded By: MIT
    Conclusion/Findings: Found higher plasma tyrosine and phenylalanine ratios and other effects on the brain.
    Hyperlink to Study: http://jn.nutrition.org/cgi/content/abstract/116/3/356
20. Year Published: 1992
    Full Reference: Aspartame Exacerbates EEG Spike Wave Discharge in Children with Generalized Absence Epilepsy, PR Camfield, CS Camfield, JM Dooley, et al;
    Funded By: Ontario Ministry of Health
    Conclusion/Findings: Neurology 1992:42:1000
    Hyperlink to Study: http://www.neurology.org/cgi/content/abstract/42/5/1000
21. Year Published: 1993
    Full Reference: The Effect of Food Chemicals on Cell Aging of Human Diploid Cells in Vitro Culture, Kasamaki A and Urasawa S, The Journal of Toxicological Sciences, 1993 Aug; 18(3):143-53
    Funded By: Toxicological Sciences, 1993 Aug; 18(3):143-53. Sapporo
    Conclusion/Findings: Showed aging of cells when treated with aspartame.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/8246307
22. Year Published: 1994
    Full Reference: Neuropharmacological Evaltuation of Movement Disorders that are Adverse Reactions to Specific Foods Including Aspartame, John W. Gerrard, J Steven Richardson and Jeffrey Donat; International Journal of Neuroscience, 1994, Vol. 76, No. 1-2, pp. 61-69
    Funded By: University of Saskatchewan, Canada
    Conclusion/Findings: Shows that in susceptible individuals, certain foods or additives, including aspartame, can trigger movement disorders through an action on dopamine and other neurotransmitter pathways in the brain.
    Hyperlink to Study: http://informahealthcare.com/doi/abs/10.3109/00207459408985992
23. Year Published: 1995
    Full Reference: Effects of Aspartame on 45 CA Influx and LDH Leakage from Nerve Cells in Culture, Sonnewald U, Unsgard G, Petersen SB; Neuropharmacology and Neurotoxicology, 1995, Vol. 6, Issue 2
    Funded By: Research Council of Norway
    Conclusion/Findings: Showed signs of severe cell damage and other neurological events with aspartame.
    Hyperlink to Study:http://journals.lww.com/neuroreport/Abstract/1995/01000/Effects_of_aspartame_on_45Ca_influx_and_LDH.23.aspx
24. Year Published: 1996
    Full Reference: Increasing Brain Tumor Rates: Is There A Link to Aspartame? JW Olney, Nuri B Farber, et al.; Journal of Neuropathology & Experimental Neurology, Nov. 1996, Vol. 55, Issue 11
    Funded By: NIH
    Conclusion/Findings: Evidence implicates aspartame as a causative agent of high incidence of brain tumors in aspartame-fed rats.
    Hyperlink to Study:http://journals.lww.com/jneuropath/Abstract/1996/11000/Increasing_Brain_Tumor_Rates__Is_There_a_Link_to.2.aspx
25. Year Published: 1998
    Full Reference: Formaldehyde Derived from Dietary Aspartame Binds to Tissues Components in Vivo, C. Trocho, R. Pardo, I. Rafecas, et al
    Funded By: University of Barcelona, Spain
    Conclusion/Findings: Showed that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts.
    Hyperlink to Study: http://www.wnho.net/formaldehyde_from_aspartame.pdf

Health Problem: Headache/Migraines

26. Year Published: 1985
    Full Reference: Aspartame: Possible Effect on Seizure Susceptibility. Wurtman, RJ. Lancet. Vol. 2, no. 8463, 1060 p. 1985
    Funded By: MIT
    Conclusion/Findings: Woman who drank large amounts of Diet Coke and other aspartame-flavored beverages experienced headaches, nausea, visual hallucinations, and a grand-mal seizure.
    Hyperlink to Study: http://md1.csa.com/partners/viewrecord.php?requester=gs&collection=ENV&recid=1354938&q=Aspartame%3A+Possible+Effects+on+Seizure+Suspectibility&
    uid=789675711&setcookie=yes
27. Year Published: 1987
    Full Reference: The Effect of Aspartame on Migraine Headache. Shirley M. Koehler, Alan Glaros. Headache: The Journal of Head and Face Pain. Vol 28, Issue 1, Nov. 12, 1987
    Funded By: Not known
    Conclusion/Findings: Ingestion of aspartame by migraine sufferers causes significant increases in headache frequency
    Hyperlink to Study: http://www3.interscience.wiley.com/journal/119449495/abstract
28. Year Published: 1998
    Full Reference: Aspartame as a Dietary Trigger of Headache. Richard B. Lipton, MD, Lawrence C. Newman, MD, Joel S. Cohen, MD, Seymour Solomon, MD. The Journal of Head and Face Pain. Vol. 29, Issue 2, pp. 90-92. Sept. 1998
    Funded By
    Conclusion/Findings: Finds that aspartame may be an important dietary trigger of headache in some people.
    Hyperlink to Study: http://www3.interscience.wiley.com/journal/119429393/abstract
29. Year Published: 1991
    Full Reference: Platelet Glycine, Glutamate and Aspartate in Primary Headache, D'Andrea, G., et al., 1991. Cephalalgia, Vol. 11, pp. 197-200.
    Funded By: Not known
    Conclusion/Findings: High levels of these amino acids were found in patients with migraine with aura compared to normal subjects and other headache groups
    Hyperlink to Study: http://cep.sagepub.com/content/11/4/197.abstract
30. Year Published: 1997
    Full Reference: Chewing Gum Headaches, Blumenthal, H.J., D.A. Vance, Headache, Volume 37, Number 10, pages 665-666. 1997
    Funded By: Department of Neurology, University of Oklahoma College of Medicine, Tulsa
    Conclusion/Findings: Chewing gum with aspartame provokes headaches
    Hyperlink to Study: http://www3.interscience.wiley.com/journal/119166706/abstract
31. Year Published: 2003
    Full Reference: The Diet Factor in Pediatric and Adolescent Migraine, Millichap JG, Yee MM. Pediatric Neurology, 2003 Jan;28(1):9-15
    Funded By: Not known
    Conclusion/Findings: Aspartame is one of the substances that trigger migraines in children and adolescents
    Hyperlink to Study: http://www.drcordas.com/education/Headaches/1doc.pdf
32. Year Published: 1994
    Full Reference: Aspartame Ingestion and Headaches: a Randomized Crossover Trial. S. K. Van Den Eeden, PhD, T. D. Koepsell, MD, MPH, W. T. Longstreth, Jr., MD, MPH, G. van Belle, PhD, J. R. Daling, PhD and B. McKnight, PhD, American Academy of Neurology, Neurology. 1994;44:1787
    Funded By: University of Washington
    Conclusion/Findings: This experiment provides evidence that, among individuals with self-reported headaches after ingestion of aspartame, a subset of this group report more headaches when tested under controlled conditions. It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption.
    Hyperlink to Study: http://www.neurology.org/cgi/content/abstract/44/10/1787?ijkey=4b59bcfcba6c01af70844762469ca00f7f358c5f&keytype2=tf_ipsecsha
33. Year Published: 1990
    Full Reference: The Concept of Migraine as a State of Central Neuronal Hyperexcitability, KMA Welch, et all, 1990. Headache, Vol. 8, No. 4, pp 817-828.
    Funded By: Not known
    Conclusion/Findings: Finds that aspartate can cause migraine with aura associated with a state of central neuronal hyperexcitability
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/1979655
34. Year Published: 2001
    Full Reference: Migraine MLT-Down: An Unusual Presentation of Migraine in Patients with Aspartame-Triggered Headaches. Lawrence C. Newman, Richard B. Lipton, Headache: The Journal of Head and Face Pain, Vol. 41, Issue 9, pp. 899-901
    Funded By: The Headache Institute, St. Lukes-Roosevelt Hospital Center, New York
    Conclusion/Findings: Reports that aspartame may trigger headaches in susceptible individuals, and can worsen an ongoing attack of migraine.
    Hyperlink to Study: http://www3.interscience.wiley.com/journal/120697481/abstract
35. Year Published: 1988
    Full Reference: Aspartame as a Dietary Trigger of Headache, Richard B. Lipton, Lawrence C. Newman, Joel S. Cohen, Seymour Solomon, Headache: The Journal of Head and Face Pain, Vol. 29, Issue 2, pp. 90-92
    Funded By: Department of Neurology, Albert Einstein College of Medicine, Bronx, NY
    Conclusion/Findings: Reports that some patients with migraines reported aspartame as a trigger three times more often than those with other types of headache.
    Hyperlink to Study: http://www3.interscience.wiley.com/journal/119429393/abstract

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Health Problem: Increase in hunger, body weight, BMI

36. Year Published: 1991
    Full Reference: Chen, L. N., and Parham, E. S. "College Students'Use of High-Intensity Sweeteners Is Not Consistently Associated with Sugar Consumption." J Am Diet Assoc. 91(1991): 686–90
    Funded By: Department of Human and Family Resources at Northern Illinois University
    Conclusion/Findings: In a study of high-intensity artificial sweeteners performed on college students, there was no evidence that artificial sweetener use was associated with a decrease in their overall sugar intake. These results indicate that eating arti­ficial sweeteners simply perpetuates a craving for sweets, and overall sugar consumption is not reduced—leading to further problems controlling your weight 
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/2040783
37. Year Published: 2005
    Full Reference: "New Analysis Suggests 'Diet Soda Paradox' – Less Sugar, More Weight." UT Health Center San Antonio Press Release. June 14, 2005 · Volume: XXXVIII · Issue: 24
    Funded By: University of Texas Health Science Center at San Antonio
    Conclusion/Findings: In 2005, data gathered from the 25-year long San Antonio Heart Study also showed that drinking diet soft drinks increased the likelihood of serious weight gain – far more so than regular soda.

According to Sharon Fowler, M.P.H: 
"On average, for each diet soft drink our participants drank per day, they were 65 percent more likely to become overweight during the next seven to eight years, and 41 percent more likely to become obese." 
Hyperlink to Study: http://www.uthscsa.edu/hscnews/singleformat2.asp?newID=1539

38. Year Published: 2004
    Full Reference: "A Pavlovian Approach to the Problem of Obesity," Davidson, TL and Swithers Se, International Journal of Obesity and Related Metabolic Disorders 2004 Jul;28(7):933-5.
    Funded By: Department of Psychological Science, Ingestive Behavior Research Center, Purdue University
    Conclusion/Findings: Found that rats fed artificially sweetened liquids ate more high-calorie food than rats fed high-caloric sweetened liquids. The researchers believe the experience of drinking artificially sweetened liquids disrupted the animals' natural ability to compensate for the calories in the food. 
    Hyperlink to Study:
    http://www.ncbi.nlm.nih.gov/pubmed?term=933[page]+AND+2004/07[pdat]+AND+Davidson[author]&cmd=detailssearch
39. Year Published: 1988
    Full Reference: Uncoupling Sweet Taste and Calories, Comparison of Glucose and Three Intense Sweeteners on Hunger and Food Intake. Peter J. Rogers, Jo-ASnne Carlyle, Andrew J. Hill and John E. Blundell. Physiology & Behavior. Vol. 43; Issue 5, 1988. pp. 547-552
    Funded By: Biopsychology Group, Psychology Dept., University of Leeds, Leeds UK
    Conclusion/Findings: Intense sweeteners can produce significant changes in appetite, with aspartame causing the most pronounced effects.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/3200909
40. Year Published: 1990
    Full Reference: Oral  Stimulation with Aspartame Increases Hunger, Michael G. Tordoff and Annette M. Alleva, Physiology & Behavior, Vol. 47, Issue 3, March 1990; pp. 555-559.
    Funded By: Monell Chemical Senses Center, Philadelphia
    Conclusion/Findings: Showed that aspartame can increase the feeling of hunger
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/2359769

41. Year Published: 2010
    Full Reference: Gain Weight by "Going Diet?" Artificial Sweeteners and the Neurobiology of Sugar Cravings. Qing Yang, Yale Journal of Biological Medicine, 2010 June; 83(2): 101-108. Department of Molecular, Cellular and Developmental Biology
    Funded By: Yale University
    Conclusion/Findings: Several large scale prospective cohort studies found positive correlation between artificial sweetener use and weight gain. When matched for initial body mass index (BMI), gender, ethnicity, and diet, drinkers of artificially sweetened beverages consistently had higher BMIs. Similar observations have been reported in children. Artificial sweeteners, precisely because they are sweet, encourage sugar craving and sugar dependence.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892765/?tool=pubmed

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Other Health Problems: Multiple symptoms including retinal damage, disruption of odor-associated learning, miscellaneous toxicity problems, elevations in plasma, pre-term delivery, rise in serum methanol

42. Year Published: 1985
    Full Reference: A Metabolite of Aspartame Inhibits Angiotensin Converting Enzyme. Grobelny D, Galardy RE. Biochemical & BioPhysical Research Communications. 1985: 128(2):960-964.
    Funded By: University of Kentucky
    Conclusion/Findings: Possibility exists that consuming large amounts of aspartame inhibits angiotensin converting enzyme
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/2986632
43. Year Published: 1986
    Full Reference: Serum Methanol Concentrations in Rats and in Men after a Single Dose of Aspartame," Davoli, E., et al., 1986. Food and Chemical Toxicology, Vol. 24, No. 3, pp. 187-189
    Funded By: Not known
    Conclusion/Findings: Both treatments caused a temporary rise in serum methanol. Methanol is a highly toxic alcohol commonly found in automobile windshield washer solvent, gas line antifreeze, copy machine fluid, fuel for small stoves, paint strippers, and as an industrial solvent.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/3957170
44. Year Published: 1977
    Full Reference: Effect of a Dipeptide, Aspartame, on Lactic Acid Production in Human Whole Saliva. Y. Mishiro and H. Kaneko. Journal of Dental Research, 1977 56(11):1427
    Funded By: Nippon Dental University, Japan
    Conclusion/Findings: Aspartame affects levels of saliva lactation and pH levels. 
    Hyperlink to Study: http://jdr.sagepub.com/content/56/11/1427.full.pdf
45. Year Published: 2010
    Full Reference: Intake of Artificially Sweetened Soft Drinks and Risk of Preterm Delivery: a Prospective Cohort Study of 59,334 Danish Pregnant Women. Halldorsson TI, Strom M, Petersen SB, Olsen SF, American Journal of Clinical Nutrition, June 30, 2010
    Funded By: Center for Fetal Programming, Division of Epidemiology, Statens serum Institute, Denmark
    Conclusion/Findings: There was an association between intake of artificially sweetened carbonated and noncarbonated soft drinks and an increased risk of preterm delivery.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/20592133
46. Year Published: 1987
    Full Reference: Effects of Oral Aspartame on Plasma Phenylalanine in Humans and Experimental Rodents, RJ Wurtman and TJ Maher. Journal of Neural Transmission, Vol. 70, Nos. 1-2, March 1987, pp. 169-173
    Funded By: MIT
    Conclusion/Findings: Aspartame causes greater elevations in plasma phenylalanine than plasma tyrosine in humans.
    Hyperlink to Study: http://www.springerlink.com/content/l148w94568vt33hw/
47. Year Published: 1986
    Full Reference: Acute Effects of Aspartame on Systolic Blood Pressure in Spontaneously Hypertensive Rats. P.J. Kiritsy and T.J. Maher. Journal of Neural Transmission, Vol 66, No. 2, June 1986, pp 121-128
    Funded By: Neuropharmacology Laboratory, Dept. of Pharmacology, Massachusetts College of Pharmacy and Allied Health Science, Boston
    Conclusion/Findings: Aspartame elevates blood and brain tyrosine levels, and cause neurochemical changes that lead to tyrosine-induced drop in blood pressure.
    Hyperlink to Study: http://www.springerlink.com/content/p33231m752721l5x/?p=41116b2cb5284004987aaa24f8a945c9&pi=37
48. Year Published: 1986
    Full Reference: Aspartame-Induced Uricaria. Anthony Kulczycki Jr., M.D. Annals of Internal Medicine. Feb. 1, 1986. Volv 104. No 2. pp. 207-208
    Funded By: Grant support NIH.
    Conclusion/Findings: Aspartame-induced urticaria confirmed by double-blind challenge.
    Hyperlink to Study: http://www.annals.org/content/104/2/207.extract
49. Year Published: 1989
    Full Reference: Behavioral Assessment of the Toxicity of Aspartame, Mark D. Holder, Pharmacology Biochemistry & Behavior, Vol. 32, pp. 17-26
    Funded By: Memorial University of Newfoundland
    Conclusion/Findings: Found that aspartame may have adverse effects when intrapeitoneally injected.
    Hyperlink to Study: http://pluto.huji.ac.il/~msrazy/PDF/HolderPBB89.pdf
50. Year Published: 1989
    Full Reference: Impaired Performance on Odor-Aversion Testing Following Prenatal Aspartame Exposure in the Guinea Pig, Diana L. Dow-Edwards, Louise A. Scribani and Edward P. Riley, Neuurotoxicity and Teratology, Vol. 11, Issue 4, July-August 1989, pp. 413-416
    Funded By: Dept. of Neurosurgery State University, New York
    Conclusion/Findings: These data indicate that aspartame exposure at 500 mg/kg throughout gestation disrupts odor-associative learning in 15-day-old guinea pigs.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/2796897
51. Year Published: 2006
    Full Reference: Aspartame Products as a Potential Danger to Infants, Children & Future Generations, Dr. HJ Roberts, director, Palm Beach Institute for Medical Research
    Funded By: No funding
    Conclusion/Findings: Aspartame causes a variety of disease in children including headaches, convulsions, unexplained visual loss, rashes, asthma, gastrointestinal problems, obesity, marked weight loss, hypoglycemia, diabetes, addiction (probably largely due to the methyl alcohol), hyperthyroidism, and a host of neuropsychiatric features. The latter include extreme fatigue, irritability, hyperactivity, depression, antisocial behavior (including suicide), poor school performance, the deterioration of intelligence, and brain tumors.
    Hyperlink to Study: http://www.rense.com/general70/duut.htm
52. Year Published: 1986
    Full Reference: Plasma Amino Acid Levels After Single Dose Aspartame Consumption in Phenylketonuria Mild II Hyperphenylalaninemia and Heterozygous State for Phenylkeonuria. The Journal of Pediatrics, Vol. 109, No. 4, pp. 668-671, October 1986.Benjamin Caballero, Barbara E. Mahon, Frances J. Rohr, Harvey L. Levy, and Richard J. Wurtman. M.D
    Funded By: MIT
    Conclusion/Findings: Plasma phenylalanine concentrations may increase to unacceptable levels when patients with PKU on phenylalanine-restricted diets consume aspartame-containing soft drinks or after loading doses of the sweetener
    Hyperlink to Study: http://wurtmanlab.mit.edu/static/pdf/673.pdf
53. Year Published: 1985
    Full Reference: Aspartame-Induced Granulomatous Panniculitis. Nelson Lee Novick, MD. Annals of Internal Medicine., Vol 102, No. 2, pp. 206-207
    Funded By: Mt. Sinai Medical Center; New York
    Conclusion/Findings: This report describes the first confirmed case of aspartame-induced granulomatous panniculitis

Hyperlink to Study: http://www.annals.org/content/102/2/206.short

54. Year Published: 1984
    Full Reference: Aspartame: Methanol and the Public Health. Woodrow C.Monte. Journal Applied Nutrition 36(1):42-54
    Funded By
    Conclusion/Findings: Consumption of aspartame sweetened drinks at levels commonly used to replace lost fluid during exercise yields methanol intake between 15 and 100 times normal intakes.
    Hyperlink to Study: http://www.dorway.com/wmonte.txt
55. Year Published: 1989
    Full Reference: Excitoxins: A Possible New Mechanism for the Pathogenesis of Ischemic Retinal Damage, George H. Bresnick, Archives of Opthalmology, 1989; 107(3):339-341
    Funded By: NIH
    Conclusion/Findings: Reports that aspartame is a possible mechanism to cause retinal damage.
    Hyperlink to Study: http://archopht.ama-assn.org/cgi/content/summary/107/3/339
56. Year published:  1987
    Full reference: Plasma Amino Acid Concentrations in Normal Adults Administered Aspartame in Capsules or Solution: Lack of Bioequivalence, Lewis D. Stegin, L.J. Filer Jr,  E.F. Bell, and E.E. Ziegler, Metabolism Volume 36, Issue 5 May 1987, Pages 507-512
    Funded by: Supported in part by a grant-in-aid from G.D. Searle
    Conclusion/Findings: The data indicate different plasma phenylalanine and aspartate pharmacokinetics between aspartame in solution and capsule administration of aspartame. Peak plasma phenylalanine levels were significantly higher and were reached significantly earlier when aspartame was administered in solution than when it was administered in capsules. Administration in solution also produced a significantly higher ratio of plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids. Similarly, peak plasma aspartate concentrations were significantly higher and were reached significantly earlier when aspartame was administered in solution.
    Hyperlink to study: http://www.ncbi.nlm.nih.gov/pubmed/3574137
57. Year published: 1984
    Full reference: Evaluation of Consumer Complaints Related to Aspartame Use, MK Bradstock, MK Serdula, JS Marks, RJ Barnard, NT Crane, PL Remington and FL Trowbridge, American Journal of Clinical Nutrition, November 1984, Vol 43, 464-469
    Funded by: Division of Nutrition, Center for Health Promotion and Education, Centers for Disease Control
    Conclusion/Findings: In some case reports, the symptoms may be attributable to aspartame in commonly-consumed amounts
    Hyperlink to study: http://www.ajcn.org/cgi/content/abstract/43/3/464

---

Health Problem: Seizures/Convulsions

58. Year Published: 1987
    Full Reference: Possible Neurologic Effects of Aspartame, a Widely Used Food Additive; Timothy J. Maher and Richard J. Wurtman. Environmental Health Perspectives, Vol. 75, pp 53-57, 1987
    Funded By: MIT and Federal Government
    Conclusion/Findings: Shows that aspartame can induce seizures
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1474447/pdf/envhper00434-0053.pdf
59. Year Published: 1991
    Full Reference: Interspecies and Interstrain Studies on the Increased Susceptibility to Metrazol-Induced Convulsions in Animals given Aspartame, L. Diomede, M. Romano, et al, Milan, Italy, Food and Chemical Toxicology, Vol. 29, Issue 2, 1991; pp. 101-106
    Funded By: Istituto di Richerche, Milan, Italy
    Conclusion/Findings: Showed that they are more susceptible to convulsions when given higher doses of aspartame
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/2010138

Letters and Other Commentary from Health Sources

60. Year Published: 1995
    Full Reference: Emerging Facts about Aspartame. Dr. J. Barua, Dr. A Bal. Journal of the Diabetic  Association of India. 1995; Vol. 35, No. 4
    Funded By: No funding
    Conclusion/Findings: Cites numerous studies showing dangers of aspartame
    Hyperlink to Study: http://basichealthinfo.weebly.com/uploads/4/2/5/9/425984/article-on-aspartame.pdf
61. Year Published: 2004
    Full Reference: Aspartame: An FDA-Approved Epidemic, HJ Roberts, Palm Beach Institute for Medical Research.
    Funded By: No funding
    Conclusion/Findings: Cites thousands of consumer complaints to the FDA that include serious adverse events, that the FDA and CDC refused to acknowledge as substantive.
    
62. Year Published: 1991
    Full Reference: Recurrent Vulvovaginitis Resulting from Heavy Dietary Use of Aspartame, Strathman I, The Journal of Reproductive Medicine. 1991 Aug;36(8):572
    Funded By: No funding
    Conclusion/Findings: (This is a letter; title implies that vulvovaginitis was triggered by heavy use of aspartame)
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/1941798
63. Year Published: 1985
    Full Reference: Interaction of Aspartame and Carbohydrates in an Eating Disordered Patient. Ferguson A Jr. A Letter in the American Journal of Psychiatry. 1985, Feb. 142(2):271
    Funded By: Not applicable
    Conclusion/Findings: Reports a clinical case where aspartame combined with carbohydrates causes headaches and other symptoms typical of elevated CNS level of tyrosine.
    Hyperlink to Study: http://ajp.psychiatryonline.org/cgi/reprint/142/2/271a.pdf
64. Year Published: 1995
    Full Reference: A Health Alert: Emerging Facts About Aspartame, Dr. J Barua, Dr. A Bal, The Journal of the Diabetic Association of India, 1995: Vol. 35, No. 4
    Funded By: No funding
    Conclusion/Findings: This article summarizes a number of other people's studies on aspartame.
    Hyperlink to Study: http://smfi.is/media/misc/article-on-aspartame.pdf
65. Year Published: 1996
    Full Reference: Aspartame as a Cause of Allgeric Reactions, Including Anaphylaxis, Archives of Internal Medicine, 1996; 156(9):1027
    Funded By: Not known
    Conclusion/Findings: Letter arguing that aspartame should have been included as a causative agent of allergic reactions. Cites FDA 7,300-person database of complaints.
    Hyperlink to Study: http://archinte.ama-assn.org/cgi/content/summary/156/9/1027-a
66. Year Published: Updated April 23, 2008
    Full Reference: Is Aspartame Safe? From an FDA Q&A about aspartame
    Funded By: Not applicable
    Conclusion/Findings: While denying that aspartame is an allergen, the FDA says: However, certain people with the genetic disease phenylketonuria (PKU), those with advanced liver disease, and pregnant women with hyperphenylalanine (high levels of phenylalanine in blood) have a problem with aspartame because they do not effectively metabolize the amino acid phenylalanine, one of aspartame's components. High levels of this amino acid in body fluids can cause brain damage. Therefore, FDA has ruled that all products containing aspartame must include a warning to phenylketonurics that the sweetener contains phenylalanine.
    Hyperlink to Study: http://answers.hhs.gov/questions/3011
67. Year published: 
    Full reference: Scientific Abuse in Methanol/Formaldehyde Research Related to Aspartame
    Funded by: no funding
    Conclusion/Findings: Exposes studies "proving" safety of aspartame as deceptive, erroneous, and based on industry research using outdated plasma methanol measuring tests. No date of publication.
    Hyperlink to Study: http://thetruthaboutstuff.com/pdf/%2847%29%20Scientific%20Abuse%20in%20Methanol.pdf 

---

Health Problem: Cancer

68. Year published: 2010
    Full reference:Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. American Journal of Industrial Medicine December 2010; 53(12): 1197-1206
    Conclusion/Findings:The results of the present study confirm that [aspartame] is a carcinogenic agent in multiple sites in rodents, and that this effect is induced in two species, rats (males and females) and mice (males). Autopsies revealed a significantly increased risk of liver and lung cancer.
    Hyperlink to Study: http://www.ncbi.nlm.nih.gov/pubmed/20886530© Copyright 1997-2013 Dr. Joseph Mercola. All Rights Reserved.

Fwd: NEUROLOGICAL ASPARTAME DAMAGE

NEUROLOGICAL ASPARTAME DAMAGE 

NEUROPHARMACOLOGY AND NEUROTOXICOLOGY

Volume 6 1995 (PP318-320) Rapid Communications of Oxford Ltd

Effects of aspartame on Ca influx and LDH leakage from nerve cells in culture 

Ursula Sonnewald, Tomm Muller, Geirmund Unsgard, S.B. Peterson MR-Centre, SINTEF UNIMED, N-7034 Trondheim; University of Trondheim, Dept. of Neurosurgery, University Hospital N-7006 Trondheim; Norwegian Institute of Tecnology, Drpt. of Biotecnology, N- 7034 Trondheim, Norway.

Aspartame (ASM), an artificial sweetener, was shown to dose dependently increase CA influx into and lactate dehydrogenase (LDH) leakage from murine brain cell cultures. Astrocytes were more resistant than neurones to the effects of ASM. In cerebellar granule neurones, a 20% increase in calcium was found after an incubation time of 22 h in the presence of 0.1 mM ASM; at 0.5 mM concentration, calcium influx increased 40% compared with control cultures. At a concentration of 10mM, influx was increased 13-fold after 5 h. Morphological appearance as judged by phase contrast microscopy was first visibly affected after exposure to 1mM ASM for 22 h. Citrate, another food additive, was included in the study to demonstrate that cerebellar granule neurones could tolerate 10mM additions to the medium and citrate did not cause Ca influx or morphological changes in neurones after 22 h. LDH leakage, a sign of severe cell damage, was observed at 1 mM concentrations of ASM after 22 h. Cerebral astrocytes on the other hand were more resistant and showed morphological changes, increased calcium influx and LDH leakage first at 5 mM concentrations of ASM.

Keywords:

Aspartame, Neurotoxicity, Cerebellar granule neurones, Lactate dehydrogenase leakage (LDH) Calcium influx

INTRODUCTION

Aspartame (L-aspartyl--L-phenylalanine methyl ester, ASM) is a widely used artificial sweetener in soft drinks and low calorie food. There have been reports of adverse neurological effects such as headache (1), insomnia and seizures after ingestion of aspartame, which may be attributed to the alterations in regional concentrations of catecholamines.(2) Brain phenylalanine and tyrosine were increased following ASM ingestion. (3) Studies using radioactively labelled aspartame in comparison with labelled methanol, aspartame and phenylalanine have shown the 30-40% of the total dose of aspartame of the labelled components remains in the body after 8 h; the remainder is primarily secreted through expired air. (4) Analysis of tissue distribution of orally administered isotopically labelled aspartame in the rat showed part of the label remaining in the brain for up to 24 h. (5) From these studies it was not possible to determine whether ASM or its degradation products reached the brain.

Both aspartate (6) and aspartame (7) have been shown to have excitatory activity. Olney et al (8) have shown that systemic administration of glutamatae, an excitatory amino acid, produced brain damage in a number of animal species including primates, and excitotoxic analogues such as aspartame had the same effects. (9)

In order to investigate potential toxicity of aspartame on brain cells, lactate dehydrogenase leakage and (45) Ca influx into astrocytes and neurones were measured after incubation with varying concentrations of aspartame.

Materials and Methods

Plastic tissue culture dishes were purchased form NUNC A/S (Denmark), fetal calf serum from Seralab (Sussex, UK), poly-L-lysine (mol wt. 300 000) and amino acids from Sigma (St. Louis, MO) ; 45Ca was from Amersham. All other chemicals were of the purest grade available from regular commercial sources.

Cortical astrocytes were cultured essentially as described by Hertz et al. (10) Prefrontal cortex was taken from newborn NMRI mice and passed through Nitex nylon sieves (80 um pore size) into a slightly modified Dulbecco's medium (DMEM) containing 20% (v/v) fetal calf serum and plated in NUNC 3 cm culture dishes. Medium was changed twice a week. Cells were used for experiments after 2-3 weeks in culture. Cerebellar granule cells were prepared from 7-day-old mice; (11) they have been shown to possess NMDA receptors (12) and are useful in the study of neurotoxicity. (12) Tissue samples of cerebella were exposed to mild trypsinization followed by trituration in a DNAse solution containing a soyabean trypsin inhibitor. Cells were suspended (2-3 x 106 cells ml-1) in a slightly modified DMEM with 10% (v/v fetal calf serum. Cytosine arabinoside (20 uM) was added after 48 h to prevent astrocyte proliferation. Cells were used after 7 days in culture. Prior to experiments, the incubation medium was removed and substituted with Hanks balanced salt solution without MG2+ (HBBS) containing 1.5 uCi ml-1 (45)Ca. The experiments were terminated by the removal of the incubation medium. The cells were washed five times with ice-cold phosphate-buffered saline containing 25 mM MgCl2 to displace (45) Ca bound extra-cellularly. The cells were lysed in 0.5 M HCL and the (45) Ca content was determined by liquid scintillation spectrometry. When appropriate, cell integrity in the cultures was assessed by determination of leakage of lactate dehydrogenase (LDH< EC 1.1.27) from cells into the medium, using a diagnostic kit supplied by Sigma Chemical (catalogue no. DG 1340-K). LDH was measured in cell extracts and medium and expressed as percentage of total LDH ((14)

Results and Discussion

Aspartame has been shown to dose-dependently inhibit L-(3H) glutamate binding to the N-methyl-D-aspartame (NMDA) receptor in a synaptosomal preparation from rat brain. (7) The NMDA receptor is an ionotropic glutamate receptor mediating calcium influx into neurones. Aspartate, a constituent of ASM, is a potent NMDA agonist and has been shown to induce widespread late neuronal degeneration. (14) Delayed cell death mediated by the NMDA receptor depended on the presence of extracellular calcuium. (15-17) Thus the present study was undertaken to evaluate the effect of ASM on primary nerve cell cultures in terms of calcium influx. Furthermore measurement of LDH activity released to the extracellular media has been found to be a quantitative method for determining neuronal cell injury. (18) Table 1 shows that ASM dose-and time-dependently increase calcium influx into and LDH leakage from cerebellar granule neurones. No effect was detected at 0.1 mM, but at 0.5 mM ASM LDH leakage was increased slightly and at a concentration of 5 mM LDH leakage was increased by a factor of 2.5 after 22 h (Table 1). After this time cells had detached from the culture dishes and intracellular (45)Ca could not be determined. At 10 mM, calcium influx was increased 13-fold after a 5 h incubation (Table 2). Citrate, another food additive, was included in the study to demonstrate that cerebellar granule neurones could tolerate addition of organic substances at 10 mM concentration to the medium and citrate did not cause (45) Ca influx or morphological changes in neurones; however, deleterious effects on astrocytes were seen. The above findings further confirm the hypothesis of Pan-How et al (7) that the neurotoxicity produced by ASM is mediated by a calcium coupled receptor. In the case of cerebellar granule neurones it is likely to be an NMDA receptor-mediated effect. The excitotoxin responsible for this effect could either be free aspartate (an NMDA receptor agonist) derived from proteolytic cleavage of ASM or ASM directly. Astrocytes on the other hand are not believed to have NMDA receptors and the observed calcium influx at 5 mM ASM (Table 1) must therefore be mediated through a different mechanism. LDH leakage, a sign of cell damage,was also observed in astrocytes (Table 1). Thus it has been shown that ASM has adverse effects both on glia and neurones in culture.

Clearly the concentrations used in these studies are not likely to be physiological, but subpopulations of neurones might be affected by lower doses, and long term exposure to low concentrations might produce cumulative irreversible damage. Based on the results presented here, we cannot draw any conclusions for the in vivo situation, there is the need for additional in vitro and in vivo studies, to evaluate the safety of this food additive that is consumed in increasing amounts by adults and children.

References

1. Johns Dr. Migraine provoked by aspartame. N Engl J Med 315, 456 (1986) 

2. Coulomb, RA and Sharma RS. Neurobiochemical alterations induced by the artificial sweetener aspartame. Toxicol Parmacol 83d, 79-85 (1986) 

3. Fernstrom JD, Fernstrom MH and Gillis MA. Acute effects of aspartame on large neutral amino acid and monoamines in rat brain. Life Sci 32, 1651-1658 (1983) 

4. Opperman JA. Aspartame metabolism in animals. In Stegink LD and Filer Jr. eds. Aspartame Physiology and Biochemnistry. New York: Marcel Dekker, 1984: 161-200. 

5. Matsuzawa Y and O'Hara Y. Tissue distribution of orally administered isotopically labelled aspartame in the rat. In. Stegink LD and Filer Jr. eds. Aspartame Physiology and Biochemistry. New York: Marcel Dekker, 1984; 161-200 

6. Watkins JC. Excitatory amino acid and central synaptic transmission. Trends Pharmacol 5 373-376 (1984) 

7. Pan-Hou H, Ohe Y, Sumi M et al. Effect of aspartame on NMDA sensitive L-(3H)glutamate binding sites in rat brain synaptic membranes. Brain Res 520, 351-353 (1990)

8. Olney Jw. Sharpe LG and Feigin Rd. Glutamate-induced brain damage in infant primates. J Neuropathol Exp eurol 31, 464-488 (1972) 

9. Olney JW, Sharpe LG and Feigin RD. Glutamate-induced brain damage in infant primates. J Neuropathol Exp Neurol 31, 464-488 (1972) 

10. Hertz l, Juurlink BHG, Hertz E et al. Preparation of primary cultures of mouse (rat) astrocytes. IN: Shahar A, De Vellis J, Vernadakis A, Haber B, eds. A dissection and Tissue Culture Manual of the Nervous System New York: Liss, 1989:105-108 

11. Schousboe A, Meier E, Drejer J et al. Preparation of primary cultures of mouse (rat) cerebellar granule cells. In Shahar A, De Vellis J, Vernadakis A. Haber B, eds. A Dissection and Tissue Culture Manual of the Nervous System. New York: Liss, 1989: 183-186 

12. Lysko PG, Cox JA, Vignano MA et al. Excitatory amino acid neurotoxicity at the N-methyl-E-aspartame receptor in cultured neurones; pharmacological characterization, Brain Res 499, 258-266 (1989) 

13. Frandsen AA and Schousbor A. Time and concentration dependency of the toxicity of excitatory amino acids on cerebral neurones in primary culture. Neurochem Int 10, 583-591 (1987) 

14. Choi DW. Non-NMDA receptor-mediated neuronal injury in Alzheimer's disease? Neurobial Aging 10, 605-606 (1989) 

15. Hartly DM, Kurth MC , Bjerkness L et al. Glutamate receptor-induced (45) Ca2+ accumulation in cortical cell culture correlates with subsequentneuronal accumulation in cortical cell culture correlates with subsequent neuronal degeneration. J Neursci 13 1993-2000 (1993) 

16. Sijesjo BK and Bengtsson F. Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: A unifying hypothesis. J Cereb Blood Flow Metab 9, 127-140 (1989) 

17. Eimerl S and Schramm. The quantity of calcium that appears to induce neuronal death. J Neurochem 62 1223-1226 (1994) 

18. Koh JY and Choi DW. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods 20, 83-90 (1987) 

Acknowledgements: This research was supported by the Research Council of Norway. The use of the animal facilities at the University Hospital in Trondheim are gratefully acknowledged.

Received 26 October l994; accepted 25 Nov l9

Second Norway Study:

Aspartame Brain Damage In Mice

See the original athttp://www.aspartaam.nl/artikelen_eng/nordagbl.htm Hetle & Eltervaag: 

2001 thesis abstract aspartame brain damage in mice: Sommewald 1995 study.

For thesis in Norwegian, mailed by regular mail, contact: Anne V?rnes anne.varnes@medisin.ntnu.no

"Cola light, one calorie" men hva med jhernen?

Hovedfagoppgave hosten 2001 Utfort av Arnstein

Eltervaag og Elisabeth Hetle Det medisinske

fakultet Institutt for kliniske nevrofag Trondheim Norway 10.desember 2001

The 48-page thesis has 35 references, and includes an English abstract. Faculty and helpers listed in the Forword are: Ursula Sonnewald (with 134 items in PubMed since 1988, showing a distinguished research career in biochemical studies of neurotoxins-- one of her studies on aspartame, published 1995 with three partners, Tomm Muller, Geirmund Unsgard, and S.B. Peterson, is given in full at the end of this post, with 18 references, and obviously presents much the same laboratory technique as applied in 2001 in the thesis.), Hong Qu (female qu.hong@phys.ntnu.no), and Bente Urfjell. Obviously, this team has the experience, facilities, funding, faculty support, and motivation to study the biochemistry of aspartame toxicity in detail.

ABSTRACT

Introduction: Aspartame (ASM) is a product that was originally made for diabetics, but today ASM is widely used by healthy people as an artificial sweetener in many food products.

Purpose: The main goal with this research was to see whether ASM was harmful to brain cells (cerebellar granule cells). We wanted to check if the damage to the neurons is connected to the N-methyl-D-aspartate (NMDA)-receptors on these cells.

PROCEDURE

Brain cells from 7 day old mice were used. They were cultured in 24 Petri well dishes, and different quantities of ASM were added. After 7 days, the cultures were analysed by two different tests: Lactate dehydrogenases (LDH) test, which gives a picture of cell death (LDH leakage to the medium in which the cells were cultured). 3-[4,5- dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromid (MTT) test, which can be used to analyse mitochondrial activity in living cells. To test whether the NMDA-receptor was involved in the damage done by ASM, the receptor was blocked by (?)-2-amino-5 phosphonopentanocid (AP5).

RESULTS

Our results showed damage/cell death from an added quantity of 0.06 mg/ml ASM each day for 4 days. As a comparison there is 0.24 mg/ml ASM in Cola Light. MTT- and LDH-tests showed damage to the neurons at an added quantity of 1.5 and 3.00 mg/ml ASM after 22 hours of incubation. The results also show that ASM is in part acting through the NMDA- receptor because AP5 reduced or blocked the damage to the granule cells.

CONCLUSION

In light of these results, our conclusion is that in order to be on the safe side, it should be warned against use of ASM as a food additive, maybe especially in products consumed by children, because NMDA-receptors and the synapses involved also are connected to learning.

http://www.dagbladet.no/print/?/dinside/2001/12/17/301529.html

[A major newspaper in Norway]

FARLIG FOR HJERNEN?

Medisinstudent Elisabeth Hetle (32) har sluttet ? drikke lettbrus, mens medstudent Arnstein Eltervaag (40) aldri har drukket lettbrus.

I edited this into a fairly accurate English version:

DANGER FOR BRAIN?

Medical student Elisabeth Hetle (32) has stopped using aspartame diet sodas, while fellow student Arnstein Eltervaag (40) has never used them.

You can also read this article at: [article on newspage]

http://www.dagbladet.no/dinside/2001/12/17/301529.html

Dagbladet 2001:

hetle@stud.ntnu.no eltervaa@stud.ntnu.no

(Posted by Aspartame Consumer Safety Network and Pilot Hotline (since 1987) Founder: Mary Nash Stoddard marystod@airmail.net)

Other URLs:

• https://twitter.com/#!/marystod
• http://www.marystod.blogspot.com/
• http://www.goodreads.com/author_blog_posts/2119604-cancer-risks-from-aspartame-in-studies

Recent (2011-2012) 

Radio Interviews w/Mary Nash Stoddard:

• http://ppjg.me/2012/02/10/ts-radio-with-special-guest-mary-nash-stoddard-on-aspartame/
• http://www.blogtalkradio.com/theorganicview/2011/04/05/author-mary-nash-stoddard-deadly-deception-story-of-   aspartame
• http://www.blogtalkradio.com/theorganicview/2012/01/18/mary-nash-stoddard-what-you-need-to-know-about-aspartame

Aspartame Videos:
• http://www.doctoroz.com/videos/artificial-sweeteners-and-other-food-substitutes-dangerous-your-health

• http://www.youtube.com/watch?v=ELgW4KBY-o4

•http://www.youtube.com/watch?v=p2sVe8UIEhU&list=FLLJU6TCX2cZBOqgSQt0nBig&index=1&feature=plpp_video
• http://www.youtube.com/watch?v=LgBiw_Il5YM&list=PL816E179E4563EA4B&index=1&feature=plpp_video
• http://www.youtube.com/watch?v=2mVA03IzsFM&feature=related
• http://www.youtube.com/watch?v=I-vO8aY-I4Y&feature=related
• http://www.youtube.com/watch?v=hpoAtwVyzZI&feature=related
• http://www.youtube.com/watch?v=nzJ6ZbQN9mY&feature=endscreen