RECENT PEER-REVIEWED STUDIES CRITICAL OF ASPARTAME (METHANOL, FORMALDEHYDE, FORMIC ACID)


Compiled By Rich Murray, MA
Room For All
1943 Otowi Road
Santa Fe, New Mexico 87505 USA
Telephone: 505-501-2298
E-Mail: rmforall@comcast.net
Web Site: http://health.groups.yahoo.com/group/aspartameNM



Posted: 27 August 2011


By year, recent peer-reviewed studies critical of aspartame (methanol, formaldehyde, formic acid): Rich Murray 2011.06.27

Introduction:

http://www.endthehabit.com/content/health_canada2.htm

"For example, a pack-a-day smoker will smoke 7,300 cigarettes a year and will inhale the equivalent of almost 1 gram of formaldehyde that year."

Their chart shows that smoking a pack of 20 cigarettes gives mg 0.7 -- 2.6 mg daily formaldehyde.

FEMA found 1.2 ppm formaldehyde in April 2005 in one of over 120,000 mobile homes supplied for recent hurricane victims -- 75 times more than the 0.016 level set for 8-hour working days by the National Institute for Occupational Safety and Health for workers to be required to wear respirators.

http://www.arb.ca.gov/toxics/tac/appendxc.htm

1 ppm FA in air = 1.23 mg/cubic meter, so breathing 20 cubic meters average daily air intake would retain about 20 mg FA daily, ten times the 1999 EPA alarm level for drinking water, 2 mg formaldehyde in 2 L daily drinking water.

High levels of methanol come from dark wines and liquors, as well as aspartame, above 120 mg daily for long-term heavy users, who drink 2 L daily, about 6 cans.

The aspartame quickly releases its methanol, which the ADH enzyme promptly turns into toxic formaldehyde. However, ethanol preempts the ADH enzyme, which turns ethanol into toxic acetaldehyde -- it is only after 9-13 hours in most people that blood ethanol levels become so low that the remaining blood methanol starts being converted by the ADH enzyme into formaldehyde directly in tissues next to blood capillaries.

Ingested methanol soon appears in the blood with a half-life of about 2.5 hours, so after 13 hours, the methanol blood level will be reduced 32 times to about 3% of its starting level. 2 L aspartame soft drink will give 120 mg methanol in the body (blood), dropping to about 3% in 13 hours to 3.6 mg in the body (blood). The average body has about 5.6 L blood, so the initial methanol blood level will be 20 mg/L, and after 13 hours the level will be only about 3%, about 0.6 mg/L, resulting in concentrations of formaldehyde in tissues where the ADH enzyme is concentrated: brain, liver, kidney, retina, skin, prostate, muscles, breast, womb...


J. D. Trasher et al in 1990 found many symptoms in 19 mobile home residents, living with 0.05 to 0.5 ppm formaldehyde in indoor air -- far less than the harmful 1.2 ppm levels found by FEMA in many mobile homes.

http://www.drthrasher.org/formaldehyde_1990.html full text
Jack Dwayne Thrasher, Alan Broughton, Roberta Madison.
Immune activation and autoantibodies in humans with long-term inhalation exposure to formaldehyde. Archives of Environmental Health. 1990; 45: 217-223. "Immune activation, autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term formaldehyde inhalation." PMID: 2400243

"The patients in our study had symptoms and complaints related to several organs, as described previously, (4,5,9) which were similar to symptoms of workers with multiple chemical sensitivity,(11) cacosmia,(12) and other chemical exposures. (13-15)

We report on the differences in humoral and cell-mediated immunity in humans with long-term inhalation exposure to HCHO vs. asymptomatic students (controls) who experienced short-term, periodic exposure to the chemical."

"All patients in this study had sought continuous medical attention because of multiple organ symptoms involving the central nervous system (CNS) (headaches, memory loss, difficulty completing tasks, dizziness), upper- and lower respiratory symptoms, skeletal-muscle complaints, and gastroenteritis.

Three common symptoms were expressed: (1) and initial flu-like illness from which they had not fully recovered; (2) chronic fatigue, and (3) an olfactory sensitivity to ambient conditions containing low concentrations of chemicals. (4,9,11)"

"(2.) Mobile home residents consisted of 19 patients (6 males, 13 females, mean age 41 +-20 y) who currently lived in mobile homes.

The patients had lived in their environments for 2-7 y and reported multiple symptoms. (4,9)

Measured HCHO concentrations ranged from 0.05 to 0.5 ppm at the time blood samples were taken."

Victoria Inness-Brown, 3 books and 5-part video on 2.5 year study on many large tumors in 60 rats fed NutraSweet (aspartame, dextrose, maltodextrine): Joseph Mercola: Rich Murray 2011.06.23
http://rmforall.blogspot.com/2011_06_01_archive.htm
Thursday, June 23, 2011
[At end of each long page, click on Older Posts]
http://groups.yahoo.com/group/aspartameNM/message/1627

______________________________________________

An intelligent citizen videotaped her own study at home, feeding 30 male and 30 female rats NutraSweet, at the US FDA human limit of 50 mg aspartame per kg body weight -- 3,000 mg (3 grams) for humans, about 15 12-oz diet drinks daily -- a level reached by some users.

Rodents are about ten or more times resistant to methanol (formaldehyde, formic acid) toxicity as humans -- this is why a century ago animal tests led scientists to decide that methanol was safe for humans.

http://www.ihealthtube.com/aspx/viewvideo.aspx?v=6d2705d064bf79a1

Information From: iHealthTube Admin
Added: 6/21/2011
Time: 14:17
Views: 52
Dr. Joseph Mercola speaks with Victoria Inness-Brown about artificial sweeteners, particularly aspartame. She looks at the negative effects of aspartame and why it should be avoided. This is part one of a five-part video series.
Contributor(s): Mercola, Joseph D.O.
Tags: artificial sweeteners, aspartame
Transcript: None

http://www.mpwhi.com/aspartame_study_female_rats_developed_visible_tumors.pdf
3 page summary 2011.03.03 color photos
Aspartame Study: 67% of Female Rats Developed Visible Tumors
By Victoria Inness-Brown, M.A.

http://www.aspartameexperiment.com links automatically to http://www.writerswithoutborders.net/vib/aspartame

My Aspartame Experiment: Report from a Private Citizen, is available in two versions.

The color edition provides full color photos of the results of my experiment.
https://www.createspace.com/900002308 $ 23.95 164 pages 201.04.15

The black and white edition is intended to be more affordable, though less dramatic, as all photos are in black and white.
https://www.createspace.com/900002309 $ 9.95 164 pages 2010.04.15

My newest publication called Are Your Diet Sodas Killing You? Results from My Aspartame Experiment, is an extract of the color version intended for those primarily interested in my photographic results.
https://www.createspace.com/3507100 $ 14.95 56 pages 2010.11.30
ISBN/EAN13: 1456377736 / 9781456377731

About the author:
Victoria Inness-Brown was graduated from the University of California, San Diego with bachelor's and master's degrees in mathematics. For nearly thirty years, she has worked as an award-winning technical writer for numerous high-tech companies.

My Aspartame Experiment
Report from a Private Citizen (Color Edition)
Authored by Victoria Inness-Brown, M.A.
Edited by Gini Energy, Cher Gilmore, Lalchumi Ralte, Damien Andrews, Sally Altman

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 artificial 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 2-1/2 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 results from intermixing thousands of toxic chemicals within the plant and animal kingdoms sustaining our planet.

Publication Date: Apr 15 2010
ISBN/EAN13: 1439210403 / 9781439210406
Page Count: 164
Binding Type: US Trade Paper
Trim Size: 8" x 10"
Language: English
Color: Full Color
Related Categories: Health & Fitness / Safety

http://writerswithoutborders.net/vib/victoriainnessbrown
Resume vib@writerswithoutborders.net

http://www.linkedin.com/pub/victoria-inness-brown/a/ba7/3b7

30 female pet store rats drinking lifelong 13.5 mg aspartame, 1/3 packet of Equal, had 33% with obvious tumors -- also bulging, sick, and missing eyes, paralysis, obesity, skin sores -- agrees with Ramazzini Foundation results, Victoria Inness-Brown: Murray 2008.02.15
http://rmforall.blogspot.com/2008_02_01_archive.htm
Friday, February 15, 2008
http://groups.yahoo.com/group/aspartameNM/message/1521

Aspartame, acesulfame K, saccharin, fructose each "caused accelerated senescence in human dermal fibroblasts" (re metabolic syndrome and diabetes), Kyung-Hyun Cho et al, Yeungnam University, Korea, Mol Cells. 2011 Apr 21: Rich Murray 2011.05.21
http://rmforall.blogspot.com/2011_05_01_archive.htm
Saturday, May 21, 2011
http://groups.yahoo.com/group/aspartameNM/message/1624

Aspartame doubts aired by EU MPs Corinne Lepage and Antonyia Parvanova -- EFSA National Experts agreed that "there should be more clarity about the metabolism of aspartame": Rich Murray 2011.04.24
http://rmforall.blogspot.com/2011_04_01_archive.htm
Sunday, April 24, 2011
http://groups.yahoo.com/group/aspartameNM/message/1621

Aspartame water in rats for 6 months causes liver harm, RH Nair et al, Mahatma Gandhi U, Food Chem Toxicol 2011.03.02: Rich Murray 2011.03.12
http://rmforall.blogspot.com/2011_03_01_archive.htm
Saturday, March 12, 2011
http://groups.yahoo.com/group/aspartameNM/message/1620

http://www.ncbi.nlm.nih.gov/pubmed/21376768

Food Chem Toxicol. 2011 Mar 2. [Epub ahead of print] Effect of long term intake of aspartame on antioxidant defense status in liver.
Abhilash M, Paul MV, Varghese MV, Nair RH.
School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India, 686560.
harikumarannair@hotmail.com, harinair@fastmail.fm

Careful expert lifetime study on mice shows liver and lung cancers from aspartame, M Soffritti et al, Ramazzini Institute, Italy, checked by US National Toxicology Program experts, confirms many previous studies from 2001 on: Rich Murray 2011.02.27
http://rmforall.blogspot.com/2011_02_01_archive.htm
Sunday, February 27, 2011
http://groups.yahoo.com/group/aspartameNM/message/1619

Re GC Ebers study, females harmed more by body making methanol into formaldehyde in brain via ADH enzyme: 589 references, WC Monte, retired Prof. Nutrition: Rich Murray 2011.01.08
http://rmforall.blogspot.com/2011_01_01_archive.htm
Saturday, January 8, 2011
http://groups.yahoo.com/group/aspartameNM/message/1614

Woodrow C Monte, PhD, Emiritus Prof. Nutrition gives many PDFs of research -- methanol (11% of aspartame) puts formaldehyde into brain and body -- multiple sclerosis, Alzheimer's, cancers, birth defects, headaches: Rich Murray 2010.05.13
http://rmforall.blogspot.com/2010_05_01_archive.htm
Thursday, May 13, 2010
http://groups.yahoo.com/group/aspartameNM/message/1601

[Other formaldehyde sources include alcohol drinks and tobacco and wood smoke, while adequate folic acid levels protect most people.]

http://whilesciencesleeps.com/about

http://while-science-sleeps.com/references/pdf/586
[summary, not peer reviewed]
Monte WC.
Methanol: A chemical Trojan horse as the root of the inscrutable U.
Medical Hypotheses 2010;74(3):493-6
DOI 2010.10.16

Monte WC.
Bittersweet: Aspartame Breast Cancer Link.
Fitness Life 2008 Jan. 34: 32-36

Monte WC.
A Deadly Experiment. Methanol and MS
Fitness Life 2007 Dec. 34: 36-41

Monte WC.
Sickly Sweet: Is your Diet Sweetener killing you?
Fitness Life 2007 Nov. 33: 31-33

http://whilesciencesleeps.com/references
589 references for above articles and upcoming book

http://whilesciencesleeps.com/montediet
[and Fitness Life 2007 Dec. 34: 36-41]

Methanol: Where Is It Found? How Can It Be Avoided?

AVOID the following, ranked in order of greatest danger:

  1. Cigarettes.
  2. Diet foods and drinks with aspartame.
  3. Fruit and vegetable products and their juices in bottles, cans, or pouches.
  4. Jellies, jams, and marmalades not made fresh and kept refrigerated.
  5. Black currant and tomato juice products, fresh or processed.
  6. Tomato sauces, unless first simmered at least 3 hours with an open lid.
  7. Smoked food of any kind, particularly fish and meat.
  8. Sugar-free chewing gum.
  9. Slivovitz: You can consume one alcoholic drink a day on this diet -- no more! [no fruit brandies]
  10. Overly ripe or near rotting fruits or vegetables.

Selection from Article 2, Fitness Life, December 2007, and well discussed in the DVD video:

"Identical Symptoms of MS, Methanol Poisoning and Aspartame Toxicity

The symptoms of multiple sclerosis (44, 83, 85, 169), chronic and acute methanol poisoning (13, 144, 189), and Aspartame toxicity (54, 58, 93, 181), are in all ways identical.

There is nothing that happens to the human body from the toxic effect of methanol that has not been expressed during the course of MS... nothing (143, 144).

This generalization extends even to the remarkable opthomological conditions common to both: transitory optic neuritis and retrolaminar demyelinating optic neuropathy with scotoma of the central visual field (which occasionally manifests as unilateral temporary blindness (85, 138, 163).

In fact, these opthomological symptoms have been thought of for years in their respective literatures to be "tell tale" indications for the differential diagnosis for each of these maladies independently (85, 138, 148, 163, 169).

The common symptoms of
headache (13, 83, 181, 189)
nervousness (13, 83, 181)
depression (58, 83, 189, 181)
memory loss (18, 147, 85, 169, 181)
tingling sensations (13, 85, 168, 138, 169)
pain in the extremities (13, 85, 169)
optic neuritis (85, 138, 148, 163, 169)
bright lights in the visual field (139, 83)
seizures (21, 83, 160)
inability to urinate or to keep from urinating (139, 146, 167)
are all shared by each of these conditions and shared yet again by complaints from aspartame poisoning (54, 58, 93, 181)

I take these strikingly similar symptom patterns as evidence that these disorders act on identical components of the central nervous system and in the same way.

The "Miracle" that MS shares with Methanol poisoning

In the early stages of MS, or when a non-lethal dose of methanol has been administered, complete recovery is a possibility.

The only two afflictions for which such dramatic "remissions" are reported from identical neuromuscular and opthomological damage, even "blindness" is relapsing-remitting multiple sclerosis (85) and methyl alcohol poisoning (138, 163).

The pathology of the two maladies is in may ways identical, particularly when it comes to destruction of the myelin sheath with no harm to the axon itself (18, 148, 176).

Sex Ratios for MS and Aspartame Reactions

Women bear the brunt of multiple sclerosis (91a-c) and lupus (SLE)(73) with fully three-fold representations in infliction numbers over men for both diseases.

This is exactly the proportion represented by adverse reactors to Aspartame reported by the US Center for Disease Control in their study of 1984 (58).

The Center found three women to every man whose Aspartame consumption complaints were serious enough to warrant investigation (93).

Although the female/male ratio for those stricken with MS has always been high, recent estimates place it at over 3 to 1 (91, 91a, 91c).

What might account for the difference across sexes in incidence?

A study published in the New England Journal of Medicine (94) reports biopsies of the gastric lining of men and women.

A result was that the concentration of ADH in the gastric lining of men was much higher than for woman.

Men have the advantage of removing methanol from the bloodstream four times faster on an equal-body-size basis than women.

Thus, for men, methanol is more likely to be removed from the blood before it reaches the brain.

The brain is spared but the methanol removed would still be metabolized to formaldehyde in the gut where it would reap its havoc on a more forgiving organ.

This may help explain why men have more gastrointestinal complaints from both methanol and Aspartame consumption (93, 99).

On the other hand, women's complaints from both more frequently involve serious neurological complications."...

______________________________________________

Methanol (11% of aspartame), made by body into formaldehyde in many vulnerable tissues, causes modern diseases of civilization, summary of a century of research, Woodrow C Monte PhD, Medical Hypotheses journal: Rich Murray 2009.11.15
http://rmforall.blogspot.com/2009_11_01_archive.htm
Sunday, November 15, 2009
http://groups.yahoo.com/group/aspartameNM/message/1589

Aspartame abstinance cures fibromyalgia chronic pain in 2 French adults: R Ciappuccini et al, Clin Exp Rheumatol 2010 Nov: Rich Murray 2010.02.19
http://rmforall.blogspot.com/2011_02_01_archive.htm

Saturday, February 19, 2011
http://groups.yahoo.com/group/aspartameNM/message/1617

Formaldehyde from 0.2 mg daily methanol from aspartame in Singulair (montelukast) chewable asthma medicine causes severe allergic dermatitis in boy, SE Jacob et al, Pediatric Dermatology 2009 Nov: Rich Murray 2010.09.27
http://rmforall.blogspot.com/2010_09_01_archive.htm
Monday, September 27, 2010
http://groups.yahoo.com/group/aspartameNM/message/1613

2011

http://www.ncbi.nlm.nih.gov/pubmed/21533907

Mol Cells. 2011 Apr 21. [Epub ahead of print]
Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state.
Jang W, Jeoung NH, Cho KH. Source
School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, Korea. chok@yu.ac.kr

[Correspondence to: Dr Kyung-Hyun Cho, School of Biotechnology, Aging-associated Vascular Disease Research Center, Yeungnam University, Gyeongsan, 712-749, Korea E-mail: chok@yu.ac.kr ]

Abstract

Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns.

However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently.

We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects.

Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure.

The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment.

They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages.

Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts.

These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL.

PMID: 21533907

http://www.ncbi.nlm.nih.gov/pubmed/21376768

Food Chem Toxicol. 2011 Mar 2. [Epub ahead of print]
Effect of long term intake of aspartame on antioxidant defense status in liver.
Abhilash M, Paul MV, Varghese MV, Nair RH.
School of Biosciences, Mahatma Gandhi University
Kottayam, Kerala, India, 686560
harikumarannair@hotmail.com, harinair@fastmail.fm
Abstract

The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats, weighing 150 - 175 g, were randomly divided into three groups as follows: first group was given aspartame dissolved in water in a dose of 500 mg/kg.b.wt; the second group was given a dose of 1000 mg/kg.b.wt; and controls were given water freely. Rats that had received aspartame (1000 mg/kg.b.wt) in the drinking water for 180 days showed a significant increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and y-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of rats that had received aspartame (1000 mg/kg.b.wt). Glutathione was significantly decreased in both the experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-treated rats (1000 mg/kg.b.wt). It can be concluded from these observations that long term consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status mainly through glutathione dependent system. Copyright 2011. Published by Elsevier Ltd. PMID: 21376768

Souganth Paul, MV - Research Fellow

Abhilash, M - Research Fellow

Mathews V Varghese - Research Fellow

http://www.mgu.ac.in/index.php?option=com_content&view=article&id=493&Itemid=96

School of Bio-Sciences Teacher Profiles

Name: Dr. R. Harikumaran Nair
Designation: Assistant Professor
Address: Room No. 5
School of Biosciences
Mahatma Gandhi University
Priyadarshini Hills. P O., Kottayam-686 560
Kerala, India
Phone: +91-481-2731035 Extension: 16
Mobile Phone: +91-94472 60362
Email: harikumarannair@hotmail.com, harinair@fastmail.fm
Home page: http://www.biophysiol.org

Research Interest

In our laboratory, we study the effect of food additives such as monosodium glutamate, aspartame, drug component arsenic trioxide and other toxins like organic solvents on different physiological mechanisms in rats and tissue culture model systems. Another area of interest is environmental and occupational stress.

Academic Profile

Ph. D - Physiology (2001), School of Biosciences
Mahatma Gandhi University, Kottayam, Kerala, India
M. Sc - Zoology (1994)
University of Kerala, Thiruvananthapuram, Kerala, India
B. Sc - Zoology (1992)
University of Kerala, Thiruvananthapuram, Kerala, India


http://www.ncbi.nlm.nih.gov/pubmed/20886530

Am J Ind Med. 2010 Sep 30. [Epub ahead of print]
Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice.
Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L, Bua L.
Cesare Maltoni Cancer Research Center, Ramazzini Institute, Bentivoglio, Bologna, Italy
Morando Soffritti MD, Fiorella Belpoggi DBS, Marco Manservigi DBS, Eva Tibaldi DBS, Michelina Lauriola PhD, Laura Falcioni DVM, Luciano Bua MD
Article first published online: 30 SEP 2010
DOI: 10.1002/ajim.20896
Copyright Â(c) 2010 Wiley-Liss, Inc.

Abstract

BACKGROUND:
Aspartame (APM) is a well-known intense artificial sweetener used in more than 6,000 products. Among the major users of aspartame are children and women of childbearing age. In previous lifespan experiments conducted on Sprague-Dawley rats we have shown that APM is a carcinogenic agent in multiple sites and that its effects are increased when exposure starts from prenatal life.

OBJECTIVE:
The aim of this study is to evaluate the potential of APM to induce carcinogenic effects in mice.

METHODS:
Six groups of 62-122 male and female Swiss mice were treated with APM in feed at doses of 32,000, 16,000, 8,000, 2,000, or 0 ppm from prenatal life (12 days of gestation) until death. At death each animal underwent complete necropsy and all tissues and organs of all animals in the experiment were microscopically examined.

RESULTS:
APM in our experimental conditions induces in males a significant dose-related increased incidence of hepatocellular carcinomas (P<0.01), and a significant increase at the dose levels of 32,000 ppm (P<0.01) and 16,000 ppm (P<0.05). Moreover, the results show a significant dose-related increased incidence of alveolar/bronchiolar carcinomas in males (P<0.05), and a significant increase at 32,000 ppm (P<0.05).

CONCLUSIONS: The results of the present study confirm that APM 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). No carcinogenic effects were observed in female mice. Am. J. Ind. Med. (c) 2010 Wiley-Liss, Inc. PMID: 20886530

Clin Exp Rheumatol. 2010 Nov-Dec;28(6 Suppl 63):S131-3. Epub 2010 Dec 22.
Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain.
Ciappuccini R, Ansemant T, Maillefert JF, , Tavernier C, Ornetti P.
Department of Rheumatology, Dijon University Hospital
Burgundy University, Faculty of Medicine, Dijon, France.
http://www.u-bourgogne.fr

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

http://onlinelibrary.wiley.com/doi/10.1111/j.1525-1470.2008.00855.x/abstract

Pediatr Dermatol. 2009 Nov-Dec;26(6):739-43.
Systematized contact dermatitis and montelukast in an atopic boy.
Castanedo-Tardan MP, González ME, Connelly EA, Giordano K, Jacob SE, Mari Paz Castanedo-Tardan, Mercedes E. González, Elizabeth A. Connelly, Kelly Giordano, Sharon E. Jacob
University of Miami, Miller School of Medicine
Department of Dermatology and Cutaneous Surgery
Miami, Florida, USA.
Article first published online: 2 APR 2009
DOI: 10.1111/j.1525-1470.2008.00855.x
(c) 2009 Wiley Periodicals, Inc.

Abstract

Upon ingestion, the artificial sweetener, aspartame is metabolized to formaldehyde in the body and has been reportedly associated with systemic contact dermatitis in patients exquisitely sensitive to formaldehyde. We present a case of a 9-year-old Caucasian boy with a history of mild atopic dermatitis that experienced severe systematized dermatitis after being started on montelukast chewable tablets containing aspartame. Patch testing revealed multiple chemical sensitivities which included a positive reaction to formaldehyde. Notably, resolution of his systemic dermatitis only occurred with discontinuation of the montelukast chewables. PMID: 20199453

2010

Am J Clin Nutr. 2010 Jun 30. [Epub ahead of print] 8 pages Intake of artificially sweetened soft drinks and risk of preterm delivery: a prospective cohort study of 59,334 Danish pregnant women.
Halldorsson TI, lur@ssi.dk; Strøm M, mrm@ssi.dk; Petersen SB, marp@sund.ku.dk; Olsen SF. sfolsen@hsph.harvard.edu
Centre for Fetal Programming, Division of Epidemiology
Statens Serum Institut, Copenhagen, Denmark, Reykjavik, Iceland.
Thorhallur I Halldorsson, Marin Strøm, Sesilje B Petersen, and Sjurdur F Olsen

Abstract

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 (<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: /=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 >/=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. PMID: 20592133

  1. From the Centre for Fetal Programming, Division of Epidemiology, Statens Serum Institut, Copenhagen, Denmark (TIH, MS, SBP, and SFO); the Unit for Nutrition Research, Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland (TIH), Reykjavik, Iceland; and the Department of Nutrition, Harvard School of Public Health. Boston, MA (SFO).

  2. Supported by the European Union (EU), Integrated Research Project, EARNEST (FOOD-CT-2005-007036). The EU project EARNEST http://www.metabolic-programming.org receives financial support from the Commission of the European Communities under the FP 6 priority 5: food quality and safety. The Danish National Birth Cohort has been financed by the March of Dimes Birth Defects Foundation, the Danish Heart Association, the Danish Medical Research Council, and the Sygekassernes Helsefond, Danish National Research Foundation, Danish Pharmaceutical Association, Ministry of Health, National Board of Health, Statens Serum Institut.

  3. Address correspondence to TI Halldorsson, Centre for Fetal Programming, Division of Epidemiology, Statens Serum Institut, Artillerivej 5, Building 206, DK-2300 Copenhagen S, Denmark. E-mail: lur@ssi.dk; Received November 19, 2009. Accepted for publication June 3, 2010. doi: 10.3945/ajcn.2009.28968.

Of the 59,334 pregnant women,

Over 4 artificially sweetened carbonated soft drinks daily __ 340 0.6 %

noncarbonated soft drinks __ 1,753 3.0 %

2-3 cans daily artificially carbonated _______________ 834 1.4 %

noncarbonated ___________ 3,643 6.1 %

So, over 3% of pregnant women in 1996-2002 used 4 or more artificially sweetened soft drinks daily, while over 6 % had 2-3 drinks daily.

This does not include aspartame from other foods.

"A monitoring survey from 2005 quantified artificial sweeteners in 76 soft drinks from the Danish market (30). For carbonated soft drinks, aspartame and acesulfame-K were primarily used in products from the major international brands, and the average concentration of these 2 sweeteners was around 2--3-fold higher in carbonated than in noncarbonated soft drinks (30)."

"After ingestion, aspartame is broken down into aspartic acid, phenylalanine, and methanol. Methanol is oxidized into formaldehyde and then to formic acid, which is considered responsible for the toxic effects of methanol. Despite arguments that aspartame intake should not affect blood methanol concentrations (34), animal studies have reported the accumulation of formaldehyde adducts derived from aspartame in tissue components (22). This might be one explaining factor for reports on headaches linked to the intake of aspartame (10). More relevant to our findings, a study in low dose methanol exposure through inhalation in nonhuman primates observed a significant decrease in the length of gestation in exposed animals compared with control animals (21). A shortening of gestation was even observed at methano vapor concentrations that barely affected blood methanol concentrations in these animals (200 ppm; 2.5 h/d). Furthermore, 5 out of 28 exposed animals needed medical intervention and were delivered by cesarean delivery either because of vaginal bleeding (n = 4) or unproductive labor (n = 1). None of the 9 control animals required cesarean delivery. The authors suggested that the observed shortening of gestation could either be related to the effects of methanol on the fetal neuroendocrine system (hypothalamic-pituitary-adrenal axis) or an indirect action of methanol on the maternal uterine environment. The latter explanation would be more compatible with our findings of an increased risk of medically induced preterm deliveries."

1917

WC Monte gives 1917 rabbit study that shows blood vessel thickening by formic acid, made by ADH in many tissues from methanol -- sources are canned fruits, wood & tobacco smoke, alcohol drinks, aspartame: Rich Murray 2010.07.04
http://rmforall.blogspot.com/2010_07_01_archive.htm
Sunday, July 4, 2010
http://groups.yahoo.com/group/aspartameNM/message/1608

_______________________________________________

Rich,

Yes there is a lot of thickening of connective tissue lining the vessels of individuals poisoned with methanol who live long enough for the changes to occur. This is to be expected since the layers of the veins and arteries that contain ADH are indeed the the ones that are involved in thickening. I have attached an article from 1917 -- take a look at page 770.

Woody 2010.07.03 12:36 PM MST

"My impression is that the apparent increase of the connective tissue is due not only to the fact that the parenchyma cells have disappeared, but to the actual proliferation of the fixed tissue cells, as seen by the very marked thickening of the adventitia and the media of the blood-vessels."

'In cases of long standing, in addition to the above general appearance there is also a marked increase of the connective tissue, especially around the blood-vessels."

http://whilesciencesleeps.com/references

589 references

15 Eisenberg AA.; 1917. "Visceral Changes in Wood Alcohol Poisoning by Inhalation", American Journal of Public Health 7:765

http://whilesciencesleeps.com/references/pdf/15 7 pages

[This is the time before Roe when it was unknown that humans were many times more sensitive to methanol than any other animal.

Keen eyes, a century ago, noted a progression of horrors in a variety of tissues -- worth quoting at length.]

Arthur Alexander Eisenberg, BA, MD
Director, Pathological Laboratories, St. Vincent's Charity Hospital, Cleveland.

"But Pohl (8) observed experimentally that while no bad effects followed immediately after the administration to an animal of a small dose of methyl alcohol, very serious results were noticeable a few days later, the experiment in many instances terminating fatally. If a small non-lethal dose be repeated a few times, fatal issue occurs invariably, while ethyl alcohol, similarly administered, produces no such effects.

How are we to explain such paradoxical phenomenon? Why does a substance, non-lethal in a single dose, become lethal after a few repeated doses, and vice versa? The explanation as given by Pohl is as follows: Ethyl alcohol is very rapidly oxidized in the animal body, in fact so rapidly that over 90 per cent. of it is converted to carbon dioxide and water, whereas methyl alcohol is oxidized very slowly, with the formation of formaldehyde and then formic acid.

It is formic acid and its cumulative action that is responsible for the untoward effects of methyl alcohol, the variability of individual results depending on the individual power of oxidation, the action of wood alcohol thus becoming especially dangerous in those who are ill nourished...

The histo-chemical investigations of Placet (9) show that the power of fixing methyl alcohol varies with the different tissues, the following organs being given in the order of their affinity: brain, liver, kidney and muscles. This statement of Placet finds abundant confirmation in the results of my experiments...

The most striking observation was the uniformity of lesions (practically in every case the same organs, and those only, were involved), the extent of lesions varying with the duration of time exposure, thus the fatty degeneration of the cardiac muscle or destruction of the perenchyma cells of the cerebrum being more extensive in the rabbit which had been exposed for 6 months than in the one which had inhaled wood alcohol or Columbian spirits [ more refined] for but 2 months...

...the central nervous system -- notably the cerebrum -- appears to bear the brunt of the attack, it being together with the optic nerve the most frequently as well as the most extensively involved organ. Next in frequency, but not necessarily in extent, of involvement are the kidneys, the liver, and the muscle -- the latter again showing a very marked inequality of involvement, the cardiac muscle being affected in every case while the striated and the smooth muscle were involved but in 10 per cent. of the cases...no difference between the effects of wood alcohol when imbided and when inhaled.

The lesions found in the various parts of the cerebrum, the cerebellum, the medulla and the pons consisted of different degrees of inflammatory and degenerative processes. Macroscopically the tissues appear yellowish, glistening; the line of demarcation between the grey and the white matter is not as sharp as in the control animals, in the more prolonged cases the gray matter appearing quite thinned -- the entire picture being one of a nonspecific atrophy.

Microscopically, the neurocytes are diminished, assuming a spindle-like shape, Nissl's granules also are diminished, with brownish pigment scattered here and there.

In the more severe cases the parenchyma cells are greatly reduced in numbers as well as in size. Thus, for example, the brain of the rabbit which had been exposed to the inhalation of Columbian Spirits showed practically nothing but neuroglia cells, and no trace of parenchyma cells, the latter being represented by masses of granular debris and fat droplets, partly taken up by the so-called contractile cells, i.e. leucocytes, lymphocytes, and according to Birch-Hirschfield, endothelial cells.

The different states of parenchymatous degeneration depend, of course, on the length of the exposure to which the animal has been subjected, the nuclear changes varying from the wandering of the nucleus to the periphery of the cell to the total karyolysis.

My impression is that the apparent increase of the connective tissue is due not only to the fact that the parenchyma cells have disappeared, but to the actual proliferation of the fixed tissue cells, as seen by the very marked thickening of the adventitia and the media of the blood-vessels.

The entire microscopical picture corresponds very closely to Adami's "exhaustion" condition, which is "anatomically recognized by the disappearance of cells and fibres and the secondary overgrowth of glial tissue filling in the space."

The lesions of the liver and the kidney present, both macroscopically and microscopically, the typical characteristic of albuminous degeneration (cloudy swelling) and fatty degeneration -- the increased size of the organ, softened consistence, the tissue being almost friable (etat crible), glistening yellowish color, the protoplasm being uniformly dull-grey, the outline of the cells in most cases being altered or lost. The nuclei are much smaller than they normally are, lost in many cases, and appearing as vague, shadowy structures in others. The cell bodies are filled with granular, dust-like masses.

In cases of long standing, in addition to the above general appearance there is also a marked increase of the connective tissue, especially around the blood-vessels.

The muscle cells, especially the heart, present an appearance very similar to that of the liver and the kidney, as well as both fragmentation and segmentation, in some of the cases.

The lung shows in many cases patches of broncho-pneumonia, which, however, are not uniform, either in distribution or in extent."

Alcohol Clin Exp Res. 1997 Aug; 21(5): 939-43.
Endogenous production of methanol after the consumption of fruit.
Lindinger W, Taucher J, Jordan A, Hansel A, Vogel W.
Institut fur Ionenphysik, Leopold Franzens Universitat Innsbruck, Austria.

After the consumption of fruit, the concentration of methanol in the human body increases by as much as an order of magnitude. This is due to the degradation of natural pectin (which is esterified with methyl alcohol) in the human colon. In vivo tests performed by means of proton-transfer-reaction mass spectrometry show that consumed pectin in either a pure form (10 to 15 g) or a natural form (in 1 kg of apples) induces a significant increase of methanol in the breath (and by inference in the blood) of humans. The amount generated from pectin (0.4 to 1.4 g) [400 -1400 mg] is approximately equivalent to the total daily endogenous production (measured to be 0.3 to 0.6 g/day) [300 to 600 mg] or that obtained from 0.3 liters of 80-proof brandy (calculated to be 0.5 g). [500 mg] This dietary pectin may contribute to the development of nonalcoholic cirrhosis of the liver. PMID: 9267548

[Methanol has a blood half-life of about 2.5 hours, so after 13 hours, its blood level is reduced to about 3 %, which would be 12 to 42 mg for the whole body, if the degradation of pectin by bacteria in the GI tract is fast, while slower production of methanol from pectin would produce lower peak methanol levels.

The ADH enzyme does not start to convert methanol into formaldehyde until blood levels of ethanol have become very low -- then the resulting conversion of the residual methanol into formaldehyde in specific tissues is the main cause of "morning after" hangover symptoms.

High levels of folic acid protect many people from this toxic production of formaldehyde, but not for the brain or retina.]

Alcohol Clin Exp Res. 1995 Oct; 19(5): 1147-50.
Methanol in human breath.
Taucher J, Lagg A, Hansel A, Vogel W, Lindinger W.
Institut fur Ionenphysik, Universitat Innsbruck, Austria.

Using proton transfer reaction-mass spectrometry for trace gas analysis of the human breath, the concentrations of methanol and ethanol have been measured for various test persons consuming alcoholic beverages and various amounts of fruits, respectively. The methanol concentrations increased from a natural (physiological) level of approximately 0.4 ppm up to approximately 2 ppm a few hours after eating about 1/2 kg of fruits, and about the same concentration was reached after drinking of 100 ml brandy containing 24% volume of ethanol and 0.19% volume of methanol. [24 ml = 64 mg ethanol and 0.19 ml = 0.33 mg methanol] PMID: 8561283

2009

[http://health.groups.yahoo.com/group/aspartameNM/message/1589 full text]

Methanol: A Chemical Trojan Horse as the Root of the Inscrutable U, Prepublication Copy; Medical Hypotheses [innovative articles not peer-reviewed in this journal] 06 November 2009 (10.1016/j.mehy.2009.09.059)
http://www.medical-hypotheses.com/article/S0306-9877(09)00693-8/abstract
Woodrow C. Monte PhD woodymonte@xtra.co.nz
Professor of Food Science (retired)
Arizona State University
corresponding author : Woodrow C. Monte PhD
470 South Rainbow Drive
Page, Arizona 86040
Key Words: food epidemiology; diseases of civilization; methanol; formaldehyde; aspartame; autism; multiple sclerosis; Alzheimer's; U-shaped curve.

Abstract: Until 200 years ago, methanol was an extremely rare component of the human diet and is still rarely consumed in contemporary hunter and gatherer cultures. With the invention of canning in the 1800s, canned and bottled fruits and vegetables, whose methanol content greatly exceeds that of' their fresh counterparts, became far more prevalent. The recent dietary introduction of aspartame, an artificial sweetener, 11% methanol by weight, has also greatly increased methanol consumption. Moreover, methanol is a major component of cigarette smoke, known to be a causative agent of many diseases of civilization (DOC). Conversion to formaldehyde in organs other than the liver is the principal means by which methanol may cause disease. The known sites of class I alcohol dehydrogenase (ADH I), the only human enzyme capable of metabolizing methanol to formaldehyde, correspond to the sites of origin for many DOC. Variability in sensitivity to exogenous methanol consumption may be accounted for in part by the presence of aldehyde dehydrogenase sufficient to reduce the toxic effect of formaldehyde production in tissue through its conversion to the much less toxic formic acid. The consumption or endogenous production of small amounts of ethanol, which acts as a competitive inhibitor of methanol's conversion to formaldehyde by ADH I, may afford some individuals protection from DOC.

"For both, subsequent intentional challenges with aspartame and unintentional exposures brought back each of their respective symptoms."

"After the last occurrence of her nausea, headaches, and vertigo, she has since not consumed aspartame in any product or form and has been symptom free for 22 years."

"Except for six mild reoccurrences of his symptoms within 24 hours of unintentionally consuming something with aspartame (hypoesthesia anterior to the tragus and mild tinnitus) lasting 2-4 hours, he has been symptom free for over six years now."

Cases J. 2009 Sep 15; 2: 9237.
Vestibulocochlear toxicity in a pair of siblings 15 years apart secondary to aspartame: two case reports.
Pisarik P, Kai D.
University of Oklahoma College of Medicine, Tulsa
1111 S. St. Louis Ave. Tulsa, OK 74120-5440, USA.

Abstract

INTRODUCTION:
Aspartame may have idiosyncratic toxic effects for some people; however, there are few case reports published in the medical literature. We present two case reports in a pair of siblings, one with a vestibular and the other with a cochlear toxicity to aspartame. The cochlear toxicity is the first case to be reported, while the vestibular toxicity is the second case to be reported.

CASE PRESENTATION:
A 29-year-old white female had a 20-month history of nausea and headache, progressively getting worse with time and eventually to also involve vomiting, vertigo, and ataxia. She was extensively evaluated and diagnosed with a vestibular neuronitis versus a chronic labyrinthitis and treated symptomatically with limited success. In response to a newspaper article, she stopped her aspartame consumption with total cessation of her symptoms.

Fifteen years later, her then 47-year-old white brother had a 30-month history of an intermittent, initially 5-10 minute long episode of a mild sensorineural hearing loss in his right ear that progressed over time to several hour episodes of a moderately severe high-frequency sensorineural hearing loss to include tinnitus and a hypoesthetic area in front of his right tragus. After a negative magnetic resonance scan of the brain, he remembered his sister's experience with aspartame and stopped his consumption of aspartame with resolution of his symptoms, although the very high frequency hearing loss took at least 15 months to resolve. For both, subsequent intentional challenges with aspartame and unintentional exposures brought back each of their respective symptoms.

CONCLUSION:
Aspartame had a vestibulocochlear toxicity in a pair of siblings, suggesting a genetic susceptibility to aspartame toxicity. Even though the yield may be low, asking patients with dizziness, vertigo, tinnitus, or high-frequency hearing loss about their aspartame consumption and suggesting cessation of its use, may prove helpful for some. PMID: 20126318 [PubMed - in process] PMCID: PMC2815650 Free PMC Article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815650/pdf/1757-1626-0002-0000009237.pdf 4 pages 165 KB

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815650/?tool=pubmed

Cases J. 2009; 2: 9237.
Published online 2009 September 15.
doi: 10.4076/1757-1626-2-9237.
PMCID: PMC2815650
Copyright (c)2009 Pisarik and Kai
Licensee Cases Network Ltd. licensee BioMed Central Ltd.

Vestibulocochlear toxicity in a pair of siblings 15 years apart secondary to aspartame: two case reports
Paul Pisarik 1 and Dasha Kai 2
1 University of Oklahoma College of Medicine, Tulsa
1111 S. St. Louis Ave. Tulsa, OK 74120-5440, USA
2 University Physician's Hospital
2800 E. Ajo Way, Tucson, AZ 85713, USA
Corresponding author.
Paul Pisarik: paul-pisarik@ouhsc.edu; Dasha Kai: dasha456@comcast.net
Received January 2, 2009; Accepted August 25, 2009.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction

Aspartame was approved by the United States Food and Drug Administration (FDA) in 1981 for use in dry products such as breakfast cereal and as a tabletop sweetener [1]. Later in 1983 it was approved for use in sodas and in 1995 as a general sweetener in all foods and drinks. Because of its very sweet taste, aspartame has been extensively used as a food additive. It is included in over 6000 products and consumed by 200 million people around the world [2]. Because of its ubiquity in our food supply, the FDA has received many complaints over the years that allege that aspartame was responsible for a myriad of consumers' illnesses.

A PubMed search only shows only 14 case reports or case series regarding potential aspartame toxicity. The neurotoxic reactions reported include migraines, carpal tunnel syndrome, a movement disorder of the arms and legs, an orofacial sensitivity reaction, vertigo and ataxia, and seizure and mania. This will be the first paper to show a sensorineural hearing loss temporally related to aspartame and the second to show a vestibular toxicity temporally related to aspartame [3].

Case presentation

Case report 1

The first case was a 29-year-old white non-Hispanic female nurse (one of the authors) who started experiencing nausea and vomiting 3 weeks after conceiving her first pregnancy that persisted throughout her pregnancy. Her pregnancy was complicated with a 114-pound weight gain and pre-eclampsia. Her delivery was complicated with shoulder dystocia and post partum hemorrhage. After her delivery in January 1985, her symptoms got better in that she only had nausea in the mornings that cleared by 1 or 2 P.M. She also had headaches on awakening in the morning up to 3 days a week.

She was on no medications and had no allergies to medications. She denied use of alcohol, cigarettes, or any other drugs. Her past medical history was significant for intermittent hypertension. She had multiple right eye surgeries for strabismus in the early 1960s and a tonsillectomy and adenoidectomy in 1965. She was 5 foot and 11 inches tall and weighed 165 lbs prior to her pregnancy, 264 lbs just after her delivery that decreased over the time to 180 lbs at time of her self-diagnosis.

She went to see her physician in July 1985 with these symptoms. Her physician treated her with oral prochlorperazine and meclizine; however, these medications did not have much effect on her.

In January 1986, she again saw her physician with the same complaints. The neurological exam was normal except for showing a few beats of nystagmus on lateral gaze. She was again treated symptomatically with metoclopramide and trimethobenzamide. Over the next several months, the nausea progressed to encompass the entire day along with some vomiting. In addition, she was experiencing vertigo with motion and lying in bed.

She saw her physician in June 1986 and was noted to have nonfatiguing nystagmus on looking to the right. She had audiologic testing that was normal but had an electronystagmograph (ENG) that showed a direction-fixed right-beating positional nystagmus of about six degrees. She was referred to an otolaryngologist who noted a positioning nystagmus consistent with the ENG that was easily reproduced and persistent. Radiographs of the internal auditory canals were normal. Because of the persistence of her symptoms, she was then referred to a neurologist. He ordered a brainstem auditory evoked response test and a magnetic resonance imaging scan of the brain, both of which were normal. His final diagnosis was a vestibular neuronitis versus a chronic labyrinthitis and he gave her diazepam to take as needed.

Over the next two months, her symptoms got worse to where she was experiencing problems with muscle coordination manifested by occasionally not being able to negotiate doorways and occasionally not being able to place a spoon squarely in her mouth.

In September 1986, she read a doctor-advice column in the local paper that mentioned aspartame was anecdotally associated with nausea and headaches. She had first begun to drink an aspartame-sweetened drink -- Crystal Light (R) -- right after the birth of her son and was drinking 16 to 32 ounces per day, sipping on it throughout the day. She made sure that she did not consume it during her pregnancy. After reading the article, she stopped drinking Crystal Light (R), her only source of aspartame, and within a week, she was symptom free. About a month later, she challenged herself with 8 ounces of Crystal Light (R) and within 1 to 2 hours started having nausea, headaches, and vertigo that lasted for 48 hours. About 3 to 4 weeks later she drank a 12-ounce can of Diet Pepsi (R) and within 1 hour started to have the exact same symptoms, again lasting about 48 hours. She had a recurrence of the symptoms two times after that, each time after accidentally drinking a beverage with aspartame in it. After the last occurrence of her nausea, headaches, and vertigo, she has since not consumed aspartame in any product or form and has been symptom free for 22 years.

Primary diagnosis is a vestibular neuronitis versus chronic labyrinthitis secondary to aspartame. Secondary diagnosis is nausea and vomiting of pregnancy.

Case report 2

In January of 2002 at the age of 47, a non-Hispanic white male physician (one of the authors and brother of case report 1) had an intermittent right-sided tinnitus associated with a hearing loss that would last 6-8 hours at a time. In addition, at the same time, he had a 1.5 cm diameter area of hypoesthesia in the region just anterior to the tragus of his right ear. He had noted a very minor right-sided hearing loss for at least two years prior to this, but it would never last more than for a few minutes, perhaps once a month, and he never thought much about it. There was no vertigo, nausea, headaches, or other neurological symptoms associated with this.

He was 6'3" tall and weighed 180 pounds. His past medical history was pertinent for benign prostatic hypertrophy treated with finasteride since January 1998. He had no allergies to medications. He denied use of alcohol, cigarettes, or other drugs. His past surgical history was pertinent for a tonsillectomy and adenoidectomy in 1963 and an open reduction and internal fixation of a comminuted left distal radius fracture in May of 2001 with subsequent removal of hardware in August of 2001. Family history was pertinent for a sister 15 years earlier having a vestibular neuronitis versus chronic labyrinthitis secondary to aspartame.

Between January and August 5, 2002, he had five such prolonged episodes, along with the episodes that lasted for a few minutes. On August 5th, he woke up with one such episode that lasted 10 hours before it went away. On August 8th, he had another episode that started at noon and unlike his previous episodes, lasted three days with a severe tinnitus and hearing loss. He contacted an otolaryngologist and was started on prednisone. He had an audiogram on August 9th that showed a right-sided high frequency sensorineural hearing loss (see table 1). By the time he saw the otolaryngologist on August 12th, the hearing loss resolved clinically and another audiogram was done and was much improved and similar to a previous audiogram he had done in 1987, except for a remaining 35-decibel loss at 8000 Hertz (Hz) (see table 1).

At the time of his otolaryngologist appointment, his physical exam was normal. A magnetic resonance imaging scan of the brain with and without gadolinium was normal.

Table 1

Hearing threshold levels in dB (re: ANSI-1969) of case report 2 for each ear at different points in time.

When the otolaryngologist did not have an explanation for his symptoms, the patient remembered that his sister had the adverse reaction to aspartame 15 years earlier. Up until now, he had consumed foods with aspartame, undeterred by his sister's experience. At this time, he was consuming aspartame in the form of one to two cans of Caffeine Free Diet Coke(r) along with a bowl of Fiberall (R) cereal a day. Thereafter he stopped consuming aspartame in any form. Over the next two months, he had no more severe episodes of tinnitus and hearing loss but did have two further episodes of milder right-sided tinnitus and hearing loss (30% of prior intensity) and only lasting 3-4 hours.

Thinking that it might not be due to aspartame, he drank a can of Caffeine-free Diet Coke(r) a day for four days in a row. On each of these days, he had a mild episode of right-sided tinnitus and hearing loss for 2-3 hours each day. He permanently stopped his aspartame consumption after that. He had one milder episode of tinnitus and hearing loss a couple of weeks after he finished his challenge.

Follow-up audiograms showed a slowly improving 8000 Hz hearing loss: November of 2002 showed only a 20 decibel loss compared to 1987 and November of 2003 showed a 10 decibel loss compared to 1987 (see table 1).

Primary diagnosis is tinnitus and sensorineural healing loss secondary to aspartame.

Except for six mild reoccurrences of his symptoms within 24 hours of unintentionally consuming something with aspartame (hypoesthesia anterior to the tragus and mild tinnitus) lasting 2-4 hours, he has been symptom free for over six years now.

Conclusion

Aspartame had a vestibulocochlear toxicity in a pair of siblings suggesting an idiosyncratic genetic predisposition to aspartame toxicity. In addition, the cochlear toxicity in case report 2 took at least 15 months to clear after his cessation of aspartame use suggesting that aspartame's cochlear toxicity can be long lasting.

Patients with dizziness, vertigo, tinnitus, and hearing loss present not only to otolaryngologists and neurologists, but also to primary care clinicians frequently. Even though the yield may be low, asking them about their aspartame consumption and suggesting cessation of its use, may prove helpful for some.

Abbreviations

ENG: electronystagmograph
FDA: Food and Drug Administration

Consent

Written informed consent was obtained from the patients for publication of these case reports. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

DK obtained copies of her medical records when her health clinic closed down in the late 1980s and contributed both subjective and objective findings to case report 1. PP contributed to case report 2 and did the literature search. All authors read and approved the final manuscript.

References

US FDA.
Artificial Sweeteners: No Calories ... Sweet!
FDA Consumer Magazine. July-August 2006.

Butchko HH, Stargel WW.
Aspartame: scientific evaluation in the postmarketing period.
Regul Toxicol Pharmacol. 2001;34:221-233.
doi: 10.1006/rtph.2001.1500. [PubMed]

Gulya AJ, Sessions RB, Troost TR.
Aspartame and dizziness: preliminary results of a prospective, nonblinded, prevalence and attempted cross-over study.
Am J Otol. 1992;13:438-442. [PubMed]

Articles from Cases Journal are provided here courtesy of BioMed Central

http://www.medscape.com/viewarticle/579335

Dermatitis. 2008; 19(3): E10-E11.
(c) 2008 American Contact Dermatitis Society
Formaldehyde, Aspartame, and Migraines: A Possible Connection
Sharon E. Jacob; Sarah Stechschulte
Published: 09/17/2008
[Extract]

Abstract

Aspartame is a widely used artificial sweetener that has been linked to pediatric and adolescent migraines. Upon ingestion, aspartame is broken, converted, and oxidized into formaldehyde in various tissues. We present the first case series of aspartame-associated migraines related to clinically relevant positive reactions to formaldehyde on patch testing.

Case Series

Six patients (ages 16 to 75 years) were referred for evaluation of recalcitrant dermatitis. By history, five of the patients were noted to have developed migraines following aspartame consumption; the sixth reported dermatitis flares associated with diet cola consumption of >2 liters/day.

All six patients had current environmental exposures to formaldehyde or formaldehyde-releasing preservatives in their personal hygiene products and/or regular consumption of "sugar-free food" artificially sweetened with aspartame.

Based on their histories and clinical presentations, these patients were patch-tested with the North American Contact Dermatitis Group 65-allergen Standard Screening Series and selected chemicals from the University of Miami vehicle, fragrance, bakery, and textile trays.

All six patients had positive reactions to formaldehyde, and four had additional positive reactions to formaldehyde-releasing preservatives (FRPs). Expert counseling on allergen avoidance (including avoidance of formaldehyde, FRPs, and aspartame) and alternative product recommendations were provided to the patients.

At their follow-up appointments (between 8 and 12 weeks), all the patients showed clearance of their dermatitis. Four patients (two inadvertently) resumed their consumption of aspartame and subsequently returned for an additional follow-up visit. Three of the first five patients had recurrences of both their migraines and their dermatitis; the sixth patient (who had no migraines) had a positive rechallenge dermatitis. These four patients were again counseled on avoidance regimen.

Formaldehyde, aspartame, and migraines, the first case series, Sharon E Jacob-Soo, Sarah A Stechschulte, UCSD, Dermatitis 2008 May: Rich Murray 2008.07.18
http://rmforall.blogspot.com/2008_07_01_archive.htm
Friday, July 18, 2008
http://groups.yahoo.com/group/aspartameNM/message/1553

Formaldehyde from many sources, including aspartame, is major cause of Allergic Contact Dermatitis, SE Jacob, T Steele, G Rodriguez, Skin and Aging 2005 Dec.: Murray 2008.03.27
http://rmforall.blogspot.com/2008_03_01_archive.htm
Thursday, March 27, 2008
http://groups.yahoo.com/group/aspartameNM/message/1533

"For example, diet soda and yogurt containing aspartame (Nutrasweet), release formaldehyde in their natural biological degradation.

One of aspartame's metabolites, aspartic acid methyl ester, is converted to methanol in the body, which is oxidized to formaldehyde in all organs, including the liver and eyes. 22

Patients with a contact dermatitis to formaldehyde have been seen to improve once aspartame is avoided. 22

Notably, the case that Hill and Belsito reported had a 6-month history of eyelid dermatitis that subsided after 1 week of avoiding diet soda. 22"

Avoiding formaldehyde allergic reactions in children, aspartame, vitamins, shampoo, conditioners, hair gel, baby wipes, Sharon E Jacob, MD, Tace Steele, U. Miami, Pediatric Annals 2007 Jan.: eyelid contact dermatitis, AM Hill, DV Belsito, 2003 Nov.: Murray 2008.03.27
http://rmforall.blogspot.com/2008_03_01_archive.htm
Thursday, March 27, 2008
http://groups.yahoo.com/group/aspartameNM/message/1532

Sharon E. Jacob, MD, Assistant Professor of Medicine (Dermatology)
University of California, San Diego 200 W. Arbor Drive
#8420, San Diego, CA 92103-8420
Tel: 858-552-8585 ×3504 Fax: 305-675-8317
sjacob@contactderm.net; Sarah A. Stechschulte, BA sstechschulte@gmail.com

"The results indicate that there is a significant positive association between formaldehyde exposure and childhood asthma."

http://ehp.niehs.nih.gov/docs/2009/0901143/abstract.pdf
http://ehp.niehs.nih.gov/members/2009/0901143/0901143.pdf
[Study accepted for publication, text still in process]

Formaldehyde Exposure and Asthma in Children: A Systematic Review
Gerald McGwin, Jr., Jeffrey Lienert, and John I. Kennedy, Jr.
Environmental Health Perspectives
National Institutes of Health
U.S. Department of Health and Human Services
doi: 10.1289/ehp.0901143 (available at http://dx.doi.org )
Online 6 November 2009
ehponline.org

Gerald McGwin, Jr. 1, Jeffrey Lienert 2, John I. Kennedy, Jr. 3,4
1. Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
2. Franklin and Marshall College, Lancaster, PA
3. Department of Veterans Affairs Medical Center, Birmingham, AL
4. Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
Address for correspondence: Gerald McGwin, Jr., M.S., Ph.D.
922 7th Avenue South, Suite 120, Birmingham, AL 35294
mcgwin@uab.edu 205-975-3030 (ph.); 205-975-3040 (fax)

ABSTRACT

Objective:
Despite multiple published studies regarding the association between formaldehyde exposure and childhood asthma, a consistent association has not been identified. This study reports the results of a systematic review of published literature in order to provide a more comprehensive picture of this relationship.

Data Sources:
Seven peer-reviewed studies providing quantitative results regarding the association between formaldehyde exposurre and asthma in children were identified following a comprehensive literature search. There was heterogeneity across studies with respect to the definition of asthma (e.g., self-report, physician diagnosis). The majority of studies were crosssectional in nature.

Data Extraction:
For each study, an odds ratio (OR) and 95% confidence interval (CI) for asthma was either abstracted from published results or calculated based on the data provided. Characteristics regarding the study design and population were also abstracted.

Data Synthesis:
Fixed and random effects models were used to calculate pooled ORs and 95% CIs; measures of heterogeneity were also calculated. The results of a fixed effects model produced an OR of 1.03 (95% CI 1.02-1.04), and random effects model an OR of 1.17 (95% CI 1.01-1.36), both reflecting an increase of 10 microg/m3 of formaldehyde. Both the Q and I2 statistics indicated a moderate amount of heterogeneity.

Conclusions:
The results indicate that there is a significant positive association between formaldehyde exposure and childhood asthma. Given the largely cross-sectional nature of the studies underlying this meta-analysis, there remains a need for well-designed prospective epidemiologic studies.

Key Words: asthma, children, epidemiology, formaldehyde, meta-analysis

Acknowledgements and Grant Support: None

Competing Interests Declaration: Dr. McGwin has been paid as an expert witness regarding the health effects of formaldehyde exposure.

List of abbreviations and definitions used in manuscript:
NIOSH (National Institute for Occupational Safety and Health)
ppm (parts per million)
ppb (parts per billion)
OR (odds ratio)
CI (confidence interval)

Article Descriptor: asthma

Outline of Section Headers
Abstract
Introduction
Methods
Results
Discussion
Conclusion
References
Tables
Figure Legends
Figures

http://www.eyes.uab.edu/directory/mcgwin.html

Gerald McGwin, Jr., PhD
Professor and Vice Chair of Epidemiology

Address:
Department of Ophthalmology
University of Alabama at Birmingham
Callahan Eye Foundation Hospital
700 S. 18th Street, Suite 609
Birmingham, AL 35294-0009
Phone: (205) 325-8117 Fax: (205) 325-8692
E-mail: mcgwin@uab.edu

Gerald McGwin, Jr. is originally from Portland, Maine. He received his B.S. degree from the University of Vermont (1993) majoring in Education. He received an M.S. degree in Health and Social Behavior from the Harvard University School of Public Health (1995) and a Ph.D. degree in Epidemiology from the University of Alabama at Birmingham (1998). Throughout his academic training, Dr. McGwin's research interests focused on injuries, particularly as they relate to elderly populations.

Since 1998 Dr. McGwin has been on the faculty of the University of Alabama at Birmingham, where he is currently Professor and Vice Chair of Epidemiology with secondary appointments in the Departments of Ophthalmology and Surgery. His current research interests focus on the epidemiology of injuries, particularly motor vehicle collisions and burns, aging-related eye diseases, and lupus.

John I. Kennedy, Jr., M.D.
Associate Chief of Staff -- Acute & Specialty Care
Chief, Medical Service, Birmingham VA Medical Ctr.
UAB Hospital
1802 6th Avenue South
Birmingham, AL 35249
(205) 934-9999
Specialty: Allergy and Asthma, Pulmonary
Allergy and Critical Care Medicine
Hospital Affiliations: UAB Hospital
Faculty Title: Professor
School of Medicine: Southwestern Medical School, 1981
Internship: University of Alabama at Birmingham From 1981 To 1982
Residencies: University of Alabama at Birmingham From 1982 To 1984
Fellowships: University of Alabama at Birmingham From 1984 To 1986
Certifications: American Board of Critical Care Medicine, 1987
American Board of Internal Medicine, 1984
American Board of Pulmonary Medicine, 1986
Diseases Treated/Clinical Interests: Critical care medicine, interstitial lung disease, COPD, pulmonary thromboembolic disease.

"Lin's team looked at the cumulative average beverage intake, derived from food questionnaires completed in 1984, 1986, and 1990. The women replied whether they drank the beverages less than once a month, one to four times a month, two to six times weekly, once daily but less than twice, or twice a day or more often."

[Aspartame, approved in the USA for beverages in July, 1983, was by far the dominant artificial sweetener in beverages in 1984 to 1990.]

3,267 women, median age 67 in 2000, in Nurses Health Study:

"When the researchers compared kidney function of the women in 1989 and 2000, they found that 11.4% or 372 women had a kidney function decline of 30% or more. When they looked at the diet information, they found that the 30% decline in kidney function was associated with drinking two or more artificially sweetened sodas a day. This was true even after taking into account factors such as age, high blood pressure, diabetes, and physical activity."

http://www.modernmedicine.com/modernmedicine/Modern+Medicine+Now/ASN-Sodium-Swee\teners-and-Fructose-Raise-HealthRi/ArticleNewsFeed/Article/detail/638324?contextCategoryId=40137

Study presented at the American Society of Nephrology's 42nd Annual Meeting and Scientific Exposition, held from Oct. 27 to Nov. 1 in San Diego

In separate studies, Julie Lin, M.D., and Gary Curhan, M.D., of Brigham and Women's Hospital in Boston, and colleagues examined the effects of sodium and artificial sweeteners on kidney function among more than 3,000 women in the Nurses Health Study. Higher dietary sodium intake was found to be associated with a greater kidney function decline in women with well-preserved kidneys, while the odds for kidney decline doubled for women consuming two or more daily servings of artificially sweetened soda.

"While more study is needed, our research suggests that higher sodium and artificially sweetened soda intake are associated with greater rate of decline in kidney function," Lin said in a statement.

http://www.webmd.com/news/20091102/diet-sodas-hard-on-the-kidneys

Diet Sodas May Be Hard on the Kidneys Women Who Drink 2 or More Diet Sodas Daily Double Their Risk of Kidney Function Decline, Study Shows By Kathleen Doheny WebMD Health News Reviewed by Louise Chang, MD Nov. 2, 2009 -- Diet soda may help keep your calories in check, but drinking two or more diet sodas a day may double your risk of declining kidney function, a new study shows.

Women who drank two or more diet sodas a day had a 30% drop in a measure of kidney function during the lengthy study follow-up, according to research presented Saturday at the annual meeting of the American Society of Nephrology in San Diego.

"Thirty percent is considered significant,'' says researcher Julie Lin, MD, MPH, assistant professor of medicine at Harvard Medical School and a staff physician at Brigham and Women's Hospital in Boston. That's especially true, she says, because most study participants had well-preserved kidney function at the start of the study.

Diet Soda and Kidneys: Study Details
The researchers evaluated 3,256 women already participating in the Nurses' Health Study who had submitted dietary information, including their intake of sugary beverages -- sugar-sweetened drinks, sugar-sweetened soda, and artificially sweetened soda. Sugar-sweetened drinks included soda, fruit juices, punch, and iced tea.

Information was also available on measures of kidney function. Their median age was 67.

Lin's team looked at the cumulative average beverage intake, derived from food questionnaires completed in 1984, 1986, and 1990. The women replied whether they drank the beverages less than once a month, one to four times a month, two to six times weekly, once daily but less than twice, or twice a day or more often.

Diet Soda and Kidneys: Study Results
When the researchers compared kidney function of the women in 1989 and 2000, they found that 11.4% or 372 women had a kidney function decline of 30% or more. When they looked at the diet information, they found that the 30% decline in kidney function was associated with drinking two or more artificially sweetened sodas a day. This was true even after taking into account factors such as age, high blood pressure, diabetes, and physical activity.

Put another way: the women who drank two or more diet sodas a day had a decline in their glomerular filtration rate, a measure of kidney function, of 3 milliliters per minute per year. "With natural aging, kidney function declines about 1 mL per minute per year after age 40," Lin says. No link was found with the other beverages. And less than two sodas a day didn't seem to hurt. "We didn't see any association up to two artificially sweetened beverages a day," Lin says.

"A serving was reported as either a glass, a can, or a bottle of a beverage," Lin tells WebMD. "It was not more specific than that."

"The mechanisms aren't clear," Lin says of the association mshe found. In another study she presented at the meeting, she found higher salt intake is also associated with faster kidney function decline.

All of the participants were women, so Lin can't say for sure that the association holds for men, although she says there is "no biological reason to think it wouldn't."

About 20 million Americans have some evidence of chronic kidney disease, according to the society. Kidney disease diagnoses have doubled each of the last two decades. [4X more in 20 years]

http://news.yahoo.com/s/livescience/20090825/sc_livescience/obesepeoplehaveseverebraindegeneration

Obese People Have 'Severe Brain Degeneration'

hyyp://www.livescience.com - Tue Aug 25, 10:35 am ET

A new study finds obese people have 8 percent less brain tissue than normal-weight individuals. Their brains look 16 years older than the brains of lean individuals, researchers said today.

Those classified as overweight have 4 percent less brain tissue and their brains appear to have aged prematurely by 8 years.

The results, based on brain scans of 94 people in their 70s, represent "severe brain degeneration," said Paul Thompson, senior author of the study and a UCLA professor of neurology.

"That's a big loss of tissue and it depletes your cognitive reserves, putting you at much greater risk of Alzheimer's and other diseases that attack the brain," said Thompson. "But you can greatly reduce your risk for Alzheimer's, if you can eat healthily and keep your weight under control." The findings are detailed in the online edition of the journal Human Brain Mapping.

Obesity packs many negative health effects, including increased risk of heart disease, Type 2 diabetes, hypertension and some cancers. It's also been shown to reduce sexual activity.

More than 300 million worldwide are now classified as obese, according to the World Health Organization. Another billion are overweight. The main cause, experts say: bad diet, including an increased reliance on highly processed foods.

Obese people had lost brain tissue in the frontal and temporal lobes, areas of the brain critical for planning and memory, and in the anterior cingulate gyrus (attention and executive functions), hippocampus (long-term memory) and basal ganglia (movement), the researchers said in a statement today.

Overweight people showed brain loss in the basal ganglia, the corona radiata, white matter comprised of axons, and the parietal lobe (sensory lobe).

"The brains of obese people looked 16 years older than the brains of those who were lean, and in overweight people looked 8 years older," Thompson said.

Obesity is measured by body mass index (BMI), defined as the weight in kilograms divided by the square of the height in meters. A BMI over 25 is defined as overweight, and a BMI of over 30 as obese.

The research was funded by the National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, and the American Heart Association.

Hum Brain Mapp. 2009 Aug 6. [Epub ahead of print]
Brain structure and obesity.
Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller LH, Hua X, Leow AD, Toga AW, Thompson PM.
Department of Pathology, University of Pittsburgh
School of Medicine, Pittsburgh, Pennsylvania.

Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke.

These cardiovascular afflictions increase risk for cognitive decline and dementia, but it is unknown whether these factors, specifically obesity and Type II diabetes, are associated with specific patterns of brain atrophy.

We used tensor-based morphometry (TBM) to examine gray matter (GM) and white matter (WM) volume differences in 94 elderly subjects who remained cognitively normal for at least 5 years after their scan.

Bivariate analyses with corrections for multiple comparisons strongly linked body mass index (BMI), fasting plasma insulin (FPI) levels, and Type II Diabetes Mellitus (DM2) with atrophy in frontal, temporal, and subcortical brain regions.

A multiple regression model, also correcting for multiple comparisons, revealed that BMI was still negatively correlated with brain atrophy (FDR <5%), while DM2 and FPI were no longer associated with any volume differences.

In an Analysis of Covariance (ANCOVA) model controlling for age, gender, and race, obese subjects with a high BMI (BMI > 30) showed atrophy in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus compared with individuals with a normal BMI (18.5-25).

Overweight subjects (BMI: 25-30) had atrophy in the basal ganglia and corona radiata of the WM.

Overall brain volume did not differ between overweight and obese persons.

Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects.

Obesity is therefore associated with detectable brain volume deficits in cognitively normal elderly subjects.

Hum Brain Mapp, 2009. (c) 2009 Wiley-Liss, Inc.
PMID: 19662657

http://www3.interscience.wiley.com/journal/122539667/abstract?CRETRY=1&SRETRY="0

Cyrus A. Raji 1 2, April J. Ho 3, Neelroop N. Parikshak 3, James T. Becker 4 5 6, beckerjt@upmc.edu, Oscar L. Lopez 6, lopezol@upmc.edu, Lewis H. Kuller 7, Xue Hua 3, Alex D. Leow 3, feuillet@ucla.edu, Arthur W. Toga 3, Paul M. Thompson 3 *

  1. Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
  2. Department of Radiology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
  3. Laboratory of Neuro Imaging, Department of Neurology, University of California Los Angeles, School of Medicine, Los Angeles, California
  4. Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
  5. Department of Psychology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
  6. Department of Neurology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
  7. Department of Epidemiology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania
email: Paul M. Thompson ( thompson@loni.ucla.edu )
*Correspondence to Paul M. Thompson, Professor of Neurology
Laboratory of Neuro Imaging, Department of Neurology
UCLA School of Medicine, 635 Charles E. Young Drive South, Suite 225E, Los Angeles, CA 90095-7332

Cyrus A. Raji and April J. Ho contributed equally to this work.

Funded by:
NIA
NIBIB
NCRR; Grant Number: AG016570, EB01651, RR019771
National Institute of Aging; Grant Number: AG 20098, AG05133, AG15928
American Heart Association; Grant Number: 0815465D

Keywords: brain atrophy, obesity, tensor-based morphometry

Received: 23 April 2009; Revised: 3 June 2009; Accepted: 3 July 2009

Digital Object Identifier (DOI) 10.1002/hbm.20870

Addict Biol. 2005 Dec;10(4): 351-5.
Concentration changes of methanol in blood samples during an experimentally induced alcohol hangover state.
Woo YS, Yoon SJ, Lee HK, Lee CU, Chae JH, Lee CT, Kim DJ.
Chuncheon National Hospital, Department of Psychiatry
The Catholic University of Korea, Seoul, Korea.
http://www.cuk.ac.kr/eng
sysop@catholic.ac.kr
Songsin Campus: 02-740-9714
Songsim Campus: 02-2164-4116
Songeui Campus: 02-2164-4114
http://www.cuk.ac.kr/eng/sub055.htm eight hospitals

[Han-Kyu Lee]

A hangover is characterized by the unpleasant physical and mental symptoms that occur between 8 and 16 hours after drinking alcohol.

After inducing experimental hangover in normal individuals, we measured the methanol concentration prior to and after alcohol consumption and we assessed the association between the hangover condition and the blood methanol level.

A total of 18 normal adult males participated in this study.

They did not have any previous histories of psychiatric or medical disorders. The blood ethanol concentration prior to the alcohol intake (2.26+/-2.08) was not significantly different from that 13 hours after the alcohol consumption (3.12+/-2.38).

However, the difference of methanol concentration between the day of experiment (prior to the alcohol intake) and the next day (13 hours after the alcohol intake) was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively).

A significant positive correlation was observed between the changes of blood methanol concentration and hangover subjective scale score increment when covarying for the changes of blood ethanol level (r=0.498, p<0.05).

This result suggests the possible correlation of methanol as well as its toxic metabolite to hangover. PMID: 16318957

[The toxic metabolite of methanol is formaldehyde, which in turn partially becomes formic acid -- both potent cumulative toxins that are the actual cause of the toxicity of methanol.]

This study by Jones AW (1987) found next-morning hangover from red wine with 100 to 150 mg methanol (9.5 % w/v ethanol, 100 mg/l methanol, 0.01 %). Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet soda, almost six 12-oz cans, gives 123 mg methanol (wood alcohol).

Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.
Elimination half-life of methanol during hangover.
Jones AW. wayne.jones@RMV.se
Department of Forensic Toxicology
University Hospital, SE-581 85 Linkoping, Sweden.

This paper reports the elimination half-life of methanol in human volunteers. Experiments were made during the morning after the subjects had consumed 1000-1500 ml red wine (9.5 % w/v ethanol, 100 mg/l methanol) the previous evening. [100 to 150 mg methanol] The washout of methanol from the body coincided with the onset of hangover. The concentrations of ethanol and methanol in blood were determined indirectly by analysis of end-expired alveolar air. In the morning when blood-ethanol dropped below the Km of liver alcohol dehydrogenase (ADH) of about 100 mg/l (2.2 mM), the disappearance half-life of ethanol was 21, 22, 18 and 15 min. in 4 test subjects respectively. The corresponding elimination half-lives of methanol were 213, 110, 133 and 142 min. in these same individuals. The experimental design outlined in this paper can be used to obtain useful data on elimination kinetics of methanol in human volunteers without undue ethical limitations. Circumstantial evidence is presented to link methanol or its toxic metabolic products, formaldehyde and formic acid, with the pathogenesis of hangover. PMID: 3588516

Thrasher (2001): "The major difference is that the Japanese demonstrated the incorporation of FA and its metabolites into the placenta and fetus. The quantity of radioactivity remaining in maternal and fetal tissues at 48 hours was 26.9 % of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde.
[100 references]
Thrasher JD, Kilburn KH. toxicology@drthrasher.org
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html

http://www.drthrasher.org/formaldehyde_1990.html
Jack Dwayne Thrasher, Alan Broughton, Roberta Madison.
Immune activation and autoantibodies in humans with long-term inhalation exposure to formaldehyde. Archives of Environmental Health. 1990; 45: 217-223. "Immune activation, autoantibodies, and anti-HCHO-HAS antibodies are associated with long-term formaldehyde inhalation." PMID: 2400243

Clin J Pain. 2009 Jun; 25(5): 446-52.
Foods and supplements in the management of migraine headaches.
Sun-Edelstein C, Mauskop A.
The New York Headache Center, New York, NY 10021, USA. drsun@nyheadache.com
[Alexander Mauskop, MD, Director, 30 East 76th Street, New York, NY 10021
Telephone: 877-669-4323
Westchester: 99 Maple Avenue, White Plains, NY 10605
Tel: 212-794-3550
http://www.nyheadache.com/blog/ Alexander Mauskop's blog

http://www.thedailyheadache.com/2008/01/mauskop-blog.html ]

OBJECTIVE:
Although a wide range of acute and preventative medications are now available for the treatment of migraine headaches, many patients will not have a significant improvement in the frequency and severity of their headaches unless lifestyle modifications are made.

Also, given the myriad side effects of traditional prescription medications, there is an increasing demand for "natural" treatment like vitamins and supplements for common ailments such as headaches.

Here, we discuss the role of food triggers in the management of migraines, and review the evidence for supplements in migraine treatment.

METHODS:
A review of the English language literature on preclinical and clinical studies of any type on food triggers, vitamins, supplements, and migraine headaches was conducted.

RESULTS:
A detailed nutritional history is helpful in identifying food triggers.

Although the data surrounding the role of certain foods and substances in triggering headaches is controversial, certain subsets of patients may b sensitive to phenylethylamine, tyramine, aspartame, monosodium glutamatenitrates, nitrites, alcohol, and caffeine.

The available evidence for the efficacy of certain vitamins and supplements in preventing migraines supports the use of these agents in the migraine treatment.

CONCLUSIONS:
The identification of food triggers, with the help of food diaries, is an inexpensive way to reduce migraine headaches.

We also recommend the use of the following supplements in the preventative treatment of migraines, in decreasing order of preference: magnesium, Petasites hybridus, feverfew, coenzyme Q10, riboflavin, and alpha lipoic acid. PMID: 19454881

http://nyheadache.com/index.php?option=com_content&task=view&id=12&Itemid=46

Alexander Mauskop, MD FAAN, DIRECTOR

Dr. Mauskop is the Director and founder of the New York Headache Center. He is board-certified in Neurology with subspecialty certification in Headache Medicine.

Dr. Mauskop has been conducting research in the field of headaches for over 20 years and has published numerous articles in scientific journals. He has delivered over 400 scientific presentations and lectures and serves as a reviewer for the New England Journal of Medicine, Neurology, Headache, and several other medical journals.

Dr. Mauskop is a Fellow of the American Academy of Neurology, Fellow of the New York Academy of Medicine and member of other professional organization. He is an Associate Professor of Neurology at SUNY - Downstate Medical Center, Past-President of the Eastern Pain Association, and, for the past 21 years, has been the Director of an annual educational symposium for physicians.

Over 200 doctors from around the world have visited the New York Headache Center to learn advanced treatment techniques, such as Botox injections, magnesium infusions, and other.

Dr. Mauskop is a licensed acupuncturist and author of The Headache Alternative: A Neurologist's Guide to Drug-Free Relief, a book published by Dell and What Your Doctor May Not Tell You About Migraines: The Breakthrough Program That Can Help End Your Pain, published by Warner Books.

He has repeatedly been chosen as one of New York magazine's Best Doctors in New York, as one of New York Times Magazine's, "Super Doctors" and as Castle and Connolly's "Best Doctors". Dr. Mauskop has appeared on local and national television shows, including Tom Brokaw's News Hour, Extra, and PBS specials, and he has been featured in Vogue, O Magazine, and many other publications. He has given lectures at institutions such as Cornell, Harvard, Columbia, NYU and Dartmouth Medical Schools, Mayo and Cleveland Clinics.

Christina Sun-Edelstein MD, Headache and Epilepsy Specialist

Dr. Christina Sun-Edelstein is a Board-Certified Neurologist with subspecialty training and experience in both Headache and Epilepsy.

She graduated from SUNY Brooklyn College of Medicine with honors, and then completed her neurology residency at Mount Sinai Medical Center in New York.

Dr. Sun-Edelstein subsequently spent a year in Melbourne, Australia as an Epilepsy Fellow at St. Vincent's Hospital, then returned to New York for her fellowship training in Headache Medicine at Roosevelt Hospital's Headache Institute.

During her Headache Fellowship, and in clinical practice since then, Dr. Sun Edelstein has accumulated a great deal of experience in diagnosing and managing headache patients. She has also participated in research trials, and has skills in developing and implementing research protocols.

Dr. Sun-Edelstein's awards and honors include the American Academy of Neurology's Resident Scholarship Award, the David Coddon Memorial Award (given by the Headache Cooperative of New England), the American Headache Society's Clinical Fellowship Award, and the American Headache Society's Travel Award. She has also been published in academic journals such as Archives of Neurology and Headache, and has written multiple headache topics for the online medical reference UptoDate.

2007

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1530-0277.2007.00541.x

Alcoholism: Clinical and Experimental Research
Volume 31 Issue 12 Page 2114-2120, December 2007

Bhushan M. Kapur, b.kapur@utoronto.ca
Arthur C. Vandenbroucke, PhD, FCACB
Yana Adamchik
Denis C. Lehotay, dlehotay@health.gov.sk.ca
Peter L. Carlen carlen@uhnres.utoronto.ca
(2007) Formic Acid, a Novel Metabolite of Chronic Ethanol Abuse, Causes Neurotoxicity, Which Is Prevented by Folic Acid
Alcoholism: Clinical and Experimental Research 31 (12), 2114-2120.
doi:10.1111/j.1530-0277.2007.00541.x

Abstract

Background:
Methanol is endogenously formed in the brain and is present as a congener in most alcoholic beverages.

Because ethanol is preferentially metabolized over methanol (MeOH) by alcohol dehydrogenase, it is not surprising that MeOH accumulates in the alcohol-abusing population.

This suggests that the alcohol-drinking population will have higher levels of MeOH's neurotoxic metabolite, formic acid (FA).

FA elimination is mediated by folic acid.

Neurotoxicity is a common result of chronic alcoholism.

This study shows for the first time that FA, found in chronic alcoholics, is neurotoxic and this toxicity can be mitigated by folic acid administration.

Objective:
To determine if FA levels are higher in the alcohol-drinking population and to assess its neurotoxicity in organotypic hippocampal rat brain slice cultures.

Methods:
Serum and CSF FA was measured in samples from both ethanol abusing and control patients, who presented to a hospital emergency department. [CSF = Cerebral Spinal Fluid]

FA's neurotoxicity and its reversibility by folic acid were assessed using organotypic rat brain hippocampal slice cultures using clinically relevant concentrations.

Results:
Serum FA levels in the alcoholics (mean ± SE: 0.416 +- 0.093 mmol/l, n = 23) were significantly higher than in controls (mean ± SE: 0.154 +- 0.009 mmol/l, n = 82) (p < 0.0002).

FA was not detected in the controls' CSF (n = 20), whereas it was >0.15 mmol/l in CSF of 3 of the 4 alcoholic cases.

Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours to the rat brain slice cultures caused neuronal death as measured by propidium iodide staining.

When folic acid (1 umol/l) was added with the FA, neuronal death was prevented. [umol = micromole]

Conclusions:
Formic acid may be a significant factor in the neurotoxicity of ethanol abuse.

This neurotoxicity can be mitigated by folic acid administration at a clinically relevant dose.

Key Words: Formic Acid, Folic Acid, Methanol, Neurotoxicity, Alcoholism.

From the Department of Clinical Pathology (BMK), Sunnybrook Health Science Centre, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada

St. Michael's Hospital (ACV), Toronto, Canada

Department of Laboratory Medicine and Pathobiology, (BMK, ACV), Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Departments of Medicine (Neurology) and Physiology (YA, PLC), Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada

And University of Saskatchewan (DLC), Saskatchewan, Canada.

Received for publication May 1, 2007; accepted September 24, 2007.

Reprint requests: Dr. Bhushan M. Kapur, Department of Clinical Pathology, Sunnybrook Health Science Centre, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada; Fax: 416-813-7562; E-mail: b.kapur@utoronto.ca

Copyright 2007 by the Research Society on Alcoholism. DOI: 10.1111/j.1530-0277.2007.00541.x
Alcoholism: Clinical and Experimental Research 2007 Dec.
Alcohol Clin Exp Res, Vol. 31, No 12, 2007: pp 2114-2120
NEUROTOXICITY AND BRAIN damage are common concomitants findings of chronic alcoholism (Carlen and Wilkinson, 1987; Carlen et al., 1981; Harper, 2007).

The cause of ethanol-induced neurotoxicity is still unclear.

We present here a novel hypothesis for neurotoxicity: increased formic acid (FA) levels produced from methanol (MeOH), whose catabolism is blocked by ethanol.

Axelrod and Daly (1965) demonstrated the endogenous formation of MeOH from S-adenosylmethionine (SAM) in the pituitary glands of humans and various other mammalian species.

Presence of MeOH in the breath of human subjects was reported by Ericksen and Kulkarni (1963).

Most alcoholic beverages also have a small amount of MeOH as a congener (Sprung et al., 1988).

As ethanol (EtOH) has a higher affinity for alcohol dehydrogenase (ADH) than MeOH, EtOH is preferentially metabolized (Mani et al., 1970).

As a result, MeOH accumulation from endogenously produced MeOH, and/or, that consumed as part of an alcoholic beverage, has been reported in concentrations up to 2 mmol/l in heavy drinkers (Majchrowicz and Mendelson, 1971).

Toxicity resulting from MeOH consumption is extensively documented in both humans and animals and has been attributed to its metabolite, FA (Benton and Calhoun, 1952; Roe, 1946, 1955; Wood, 1912; Wood and Buller, 1904).

The rate of formate oxidation and elimination is dependent on adequate levels of hepatic folic acid, particularly hepatic tetrahydrofolate (THF) (Johlin et al., 1987; Tephly and McMartin, 1974).

Significantly higher formate levels were obtained when folate-deficient animals were exposed to MeOH as compared with folate-sufficient animals (Lee et al., 1994; McMartin et al., 1975; Noker et al., 1980).

To understand ethanol's toxicity, one must consider FA produced from MeOH, and its elimination mediated by folic acid.

We postulate that in the chronically drinking patient, we will find higher levels of FA than in the nondrinking population, and that formate is neurotoxic.

We also hypothesize that treatment with folic acid, which is a critical factor in the catabolism of FA, can prevent or diminish FA neurotoxicity.

Drug Chem Toxicol. 2008; 31(4): 447-57.
Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin.
Bandyopadhyay A, Ghoshal S, Mukherjee A.
Centre of Advanced Study, Cell and Chromosome Research, Department of Botany, University of Calcutta, Kolkata, India.

Authors:
Atrayee Bandyopadhyay a; atrayee.banerjee@gmail.com; Sarbani Ghoshal b; Anita Mukherjee a

Affiliations:
a) Centre of Advanced Study, Cell and Chromosome Research, Department of Botany, University of Calcutta, Kolkata, India
b) Present address: Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA

Low-calorie sweeteners are chemicals that offer the sweetness of sugar without the calories.

Consumers are increasingly concerned about the quality and safety of many products present in the diet, in particular, the use of low-calorie sweeteners, flavorings, colorings, preservatives, and dietary supplements.

In the present study, we evaluated the mutagenicity of the three low-calorie sweeteners in the Ames/Salmonella/microsome test and their genotoxic potential by comet assay in the bone marrow cells of mice.

Swiss albino mice, Mus musculus, were orally administered with different concentrations of aspartame (ASP; 7, 14, 28, and 35 mg/kg body weight), acesulfame-K (ASK; 150, 300, and 600 mg/kg body weight), and saccharin (50, 100, and 200 mg/kg body weight) individually.

Concurrently negative and positive control sets were maintained.

The animals were sacrificed and the bone marrow cells were processed for comet assay.

The standard plate-incorporation assay was carried with the three sweeteners in Salmonella typhimurium TA 97a and TA 100 strains both in the absence and presence of the S9 mix.

The comet parameters of DNA were increased in the bone marrow cells due to the sweetener-induced DNA strand breaks, as revealed by increased comet-tail extent and percent DNA in the tail.

ASK and saccharin were found to induce greater DNA damage than ASP.

However, none could act as a potential mutagen in the Ames/Salmonella/microsome test.

These findings are important, since they represent a potential health risk associated with the exposure to these agents. PMID: 18850355

Sarbani Ghoshal
Email: sarbanighoshal@uky.edu
Title: Post-Doctoral Scholar
Department: Pharmaceutical Sciences
Address: 561 Charles T Wethington Building 40536-0200
Phone 859 323-4993 home phone 859 323-9610

http://www.psgcas.ac.in/downloads/FreePaperpresentation.pdf

POSTER PRESENTATION (11.01.2007) THURSDAY SESSION IX (4.30 TO 6.00 PM)

PP 18 Atrayee Bandyopadhyay, et.al.,
atrayee.banerjee@gmail.com
Center for Advanced Study, Cell & Chromosome Research, Dept. of Botany, Univ of Calcutta , Kolkata
DNA damage induced by Aspartame a low calorie sweet

PP 10 Ms. Salma Ghosh & Anita Mukherjee
anitamukherjee28@gmail.com
Center of Advanced Study in cell & Chromosome Research, Dept. of Botany, Univ of Calcutta, Kolkata
Evaluation of DNA damage by ophenylenediamine in Allium assay

http://www.hsph.harvard.edu/faculty/marc-weisskopf/index.html

Marc G. Weisskopf
Mark and Catherine Winkler Assistant Professor of Environmental and Occupational Epidemiology
Department of Environmental Health
Department of Epidemiology
401 Park Dr., Rm 3-104
Landmark Center, PO Box 15697
Boston, Massachusetts 02215
617.384.8872 mweissko@hsph.harvard.edu

Education:
ScB, Neuroscience, Brown University, 1989
PhD, Neuroscience, University of California, San Francisco, 1994
ScD, Epidemiology, Harvard School of Public Health, 2006
http://www.hsph.harvard.edu/faculty/marc-weisskopf/files/AAN_ALS_chem_press_release.pdf
EMBARGOED FOR RELEASE UNTIL 2:00 P.M. CT/3:00
P.M. ET, WEDNESDAY, APRIL 16, 2008
Media Contacts:
Angela Babb, (651) 695-2789, ababb@aan.com
Rachel Seroka, (651) 695-2738, rseroka@aan.com
AAN Press Room 179B (April 12â?"18): (312) 791-7053

http://www.youtube.com/watch?v=h3ISwNRe4Xk&feature=related
4:15 minute video by John Gever, Medscape Today
http://www.4woman.gov/News/English/614428.htm
http://www.healthfinder.gov/news/newsstory.asp?docid=614428
http://www.medicinenet.com/script/main/art.asp?articlekey=88726

"...there are only about 5,500 new cases in the United States each year."

Formaldehyde Linked to Lou Gehrig's Disease
By Randy Dotinga
HealthDay Reporter

WEDNESDAY, April 16, 2008 (HealthDay News)
New preliminary research suggests that exposure to the chemical formaldehyde, present in a variety of workplaces, could greatly increase a person's chances of developing Lou Gehrig's disease.

The findings aren't definitive, and only a few thousand Americans are diagnosed with the condition -- also known as amyotrophic lateral sclerosis (ALS) - each year.

Still, the study results deserve attention, especially since formaldehyde hasn't been considered an ALS risk factor before, said study author Marc Weisskopf, an assistant professor of epidemiology and environmental health at Harvard School of Public Health. "It's a result that we view as very intriguing and worthy of follow-up."

The findings were scheduled to be released Wednesday at the American Academy of Neurology annual meeting, in Chicago.

ALS progressively causes damage to the nerve cells in the brain and spinal cord. Patients lose the ability to control their muscles, and they typically become paralyzed. There's no cure for ALS, and treatments have limited value.

Weisskopf and his colleagues examined statistics from an American Cancer Society study of more than 1 million people who were followed for 15 years.

The researchers first examined the participants' responses in 1982 to questions about exposure to 12 different chemicals, including formaldehyde. Then they followed up between 1989 and 2004 to see what happened to those people.

The researchers found that 617 men and 539 women died of ALS during the study period. Only those who reported exposure to formaldehyde had a higher risk - 34 percent higher -- of developing ALS.

Formaldehyde is used in the manufacture of a variety of products, including particle board, clothing, glues, cosmetics and shampoo. People who work in medical facilities and mortuaries may also encounter it on the job.

The pungent chemical has already been linked to higher rates of lung cancer and leukemia. It was not declared a probable human carcinogen at high exposure levels by the Environmental Protection Agency until 1987.

Those who reported more than 10 years of exposure to formaldehyde were almost four times more likely to develop ALS.

According to Weisskopf, the study design didn't allow him to estimate how many extra people may develop ALS because they are exposed to formaldehyde. However, he said there are only about 5,500 new cases in the United States each year.

Researchers have considered pesticides to be a possible cause of ALS, but formaldehyde hasn't been raised as a villain before, Weisskopf said. It's not clear how it might be linked to development of the disease, but Weisskopf said it could set off brain damage by increasing the "stress" caused by oxygen.

It's possible that other factors besides formaldehyde may be causing ALS in the study participants. Indeed, Weisskopf said the findings don't confirm a cause-and-effect relationship: "That's very hard to do. But it does provide an avenue to get more insight into the disease process, and it may give us insight that's helpful in determining other avenues to take."

Dr. Catherine Lomen-Hoerth, director of the ALS Center at the University of California, San Francisco, said it's too early for anyone to worry too much about the findings.

The research "means studies can be done in ALS rats or mice to see if formaldehyde worsens the disease process," she said, but, "I don't think we understand environmental factors very well, and in what way they affect disease processes."

"If we knew more about what causes ALS, we might know more about how formaldehydes and other chemicals might [play a role]," she added.

SOURCES: Marc Weisskopf, Ph.D., assistant professor, epidemiology and environmental health, Harvard School of Public Health, Boston; Catherine Lomen-Hoerth, M.D., Ph.D., director, ALS Center, University of California, San Francisco; April 16, 2008, presentation, American Academy of Neurology annual meeting, Chicago

Copyright (c) 2008 ScoutNews, LLC. All rights reserved.

"Regular formaldehyde exposure increased ALS risk by 34%. In addition, the longer the self-reported exposure to formaldehyde, the higher the risk for ALS. Thus, compared with those reporting no exposure, the adjusted relative risk for ALS was
1.5 in individuals who reported less than four years of exposure,
2.1 in those with four to 10 years of exposure, and
4.1 in those with more than 10 years of exposure.
Overall, 2.6% of participants reported that they had "There are several possible mechanisms for formaldehyde neurotoxicity, said Dr. Weisskopf. These include hyperexcitability of dorsal horn neurons, reduced excitability of the isolated phrenic nerve, prefrontal cortex/hippocampal neurotoxicity, a decrease in superoxide dismutase activity, an increase in malondialdehyde, and toxic tau protein misfolding."

"...other factors that might contribute to ALS were controlled for, including sex, smoking status, military service, level of education, alcohol intake, occupation, vitamin E supplement use, and exposure to other chemicals."

http://www.neurologyreviews.com/08june/FormaldehydeALS.html

Neurology Reviews.Com
Vol. 16, No. 6 June 2008

Formaldehyde Exposure May Pose Risk for Amyotrophic Lateral Sclerosis

CHICAGO -- Preliminary results suggest that exposure to the chemical formaldehyde may increase the risk for amyotrophic lateral sclerosis (ALS), according to a report at the 60th Annual Meeting of the American Academy of Neurology. Researchers found that people with more than 10 years of exposure to formaldehyde had a 4.1 times increased risk for ALS, compared with those who had no exposure.

"While pesticides have been thought to contribute to the development of ALS this is the first time that formaldehyde has been identified as a potential risk factor," commented Marc Weisskopf, PhD, Assistant Professor of Environmental and Occupational Epidemiology at Harvard School of Public Health in Boston.

Formaldehyde is used in particleboard and other wood products, permanent press fabrics, glues, photography chemicals, and other household products, such as cosmetics and shampoo. It is also used as a tissue preservative in medical laboratories and mortuaries and as an industrial disinfectant. About 20 years ago, the US Environmental Protection Agency designated high levels of formaldehyde as a probable carcinogen.

EXPOSURE TO CHEMICALS AND RISK FOR ALS

Prior research has suggested that environmental toxins, including pesticides, may be associated with ALS. This notion has been backed by case-control and genetic studies implicating genes involved in pesticide detoxification, said Dr. Weisskopf. However, the findings have been contradictory, and there have been no large prospective studies to support this hypothesis.

In the present investigation, Dr. Weisskopf's group prospectively examined the relationship between regular exposure to 12 types of chemicals and ALS in 987,229 individuals who participated in the American Cancer Society-sponsored Cancer Prevention Study II. Participants were asked about their exposure to chemicals, including formaldehyde, in 1982, and they were then followed for approximately 15 years. The researchers also analyzed exposure to asbestos, acids/solvents, coal or stone dust, coal tar pitch/asphalt, diesel engine exhaust, dyes, gasoline exhaust, pesticides/herbicides, textile fibers/dust, wood dust, and x-ray/radioactive material.

Overall, 617 men and 539 women died from ALS during the follow-up period. Regular formaldehyde exposure increased ALS risk by 34%. In addition, the longer the self-reported exposure to formaldehyde, the higher the risk for ALS. Thus, compared with those reporting no exposure, the adjusted relative risk for ALS was 1.5 in individuals who reported less than four years of exposure, 2.1 in those with four to 10 years of exposure, and 4.1 in those with more than 10 years of exposure. Overall, 2.6% of participants reported that they had been exposed to formaldehyde. By contrast, there was limited evidence for an association between ALS and pesticides/herbicides.

The study also found that an increased risk for ALS was seen with certain jobs. Nearly 25% of beauticians reported that they were exposed to formaldehyde. Pharmacists, morticians, radio/lab technicians, dentists, firemen, photographers, printers, doctors, and nurses also reported high rates of formaldehyde exposure. Individuals in these high-exposure jobs had a 28% greater risk for ALS.

There are several possible mechanisms for formaldehyde neurotoxicity, said Dr. Weisskopf. These include hyperexcitability of dorsal horn neurons, reduced excitability of the isolated phrenic nerve, prefrontal cortex/hippocampal neurotoxicity, a decrease in superoxide dismutase activity, an increase in malondialdehyde, and toxic tau protein misfolding

A CAUSAL RELATIONSHIP FOR ALS AND FORMALDEHYDE?

Dr. Weisskopf noted that the longitudinal design of the study minimizes the possibility that the results are due to bias. Additional strengths of the study include its large size and uniform case ascertainment, as well as the fact that other factors that might contribute to ALS were controlled for, including sex, smoking status, military service, level of education, alcohol intake, occupation, vitamin E supplement use, and exposure to other chemicals.

Possible limitations of the study include small numbers in some exposure categories, as well as self-assessment of exposure. In addition, only mortality data were used to identify ALS cases. Dr. Weisskopf noted, however, that because death certificates have been reported to accurately identify 70% to 80% of ALS-related deaths, they might be a reasonable surrogate for ALS incidence, due to the short survival time associated with the disease.

Dr. Weisskopf emphasized that the findings are preliminary and do not establish a causal relationship between formaldehyde and ALS. "At the moment, it is premature to make broad public health recommendations, and corroboration of the data is needed," he concluded.

NR -- Jill Stein

Suggested Reading

Morahan JM, Pamphlett R. Amyotrophic lateral sclerosis and exposure to environmental toxins: an Australian case-control study. Neuroepidemiology. 2006;27(3):130-135.

Morahan JM, Yu B, Trent RJ, Pamphlett R. A gene-environment study of the paraoxonase 1 gene and pesticides in amyotrophic lateral sclerosis. Neurotoxicology. 2007;28(3):532-540.

Neuroepidemiology. 2006; 27(3): 130-5. Epub 2006 Aug 1. Amyotrophic lateral sclerosis and exposure to environmental toxins: an Australian case-control study. Morahan JM, Pamphlett R. Department of Pathology, University of Sydney, Sydney, Australia.

It has been suggested that environmental toxins could be risk factors for sporadic amyotrophic lateral sclerosis (SALS). We therefore analysed epidemiological data on 179 SALS cases and 179 age-, ethnicity- and sex-matched controls in Australia using self-reporting questionnaires. SALS was associated with solvent/chemical exposure (OR = 1.92, 95% CI: 1.26-2.93), overall herbicide/pesticide exposure (OR = 1.57, 95% CI: 1.03-2.41) and industrial herbicide/pesticide exposure (OR = 5.58, 95% CI: 2.07-15.06). Exposure to herbicides/pesticides showed a dose-response effect. All positive findings were more statistically significant in males. These findings support those from northern hemisphere studies, indicating that environmental toxins can be risk factors for SALS. Copyright (c) 2006 S. Karger AG, Basel. PMID: 16946624

http://www.usyd.edu.au/research/opportunities/supervisors/128

Dr Morahan, Julia
position: Postdoctoral Research Fellow
department: Discipline of Pathology, School of Medical Sciences
phone: +61 2 9036 7233 fax: +61 2 9351 3429
email: morahanj@med.usyd.edu.au
location: Level 5, Room 502a
address: D06 - Blackburn
The University of Sydney
NSW 2006 Australia

Associate Professor Pamphlett, Roger
position: Associate Professor
department: Discipline of Pathology, School of Medical Sciences
phone: +61 2 9351 3318 fax: +61 2 9351 3429
email: rogerp@med.usyd.edu.au
location: Room 502A
address: D06 - Blackburn
The University of Sydney
NSW 2006 Australia

About Associate Professor Roger Pamphlett

To find a genetic cause for motor neuron disease that will enable gene therapy to halt this devastating condition.

Roger Pamphlett is a neurologist and neuropathologist who works with a team of molecular geneticists in trying to find a genetic cause for motor neuron disease.

Prof Pamphlett's research in the pathogenesis of ALS started by examining the role of environmental agents. He published 20 papers on the relationship between heavy metals and ALS, using both human tissue and animal models. This body of work showed that heavy metals enter motor neurons selectively, but that the metals by themselves are unlikely to cause ALS. This raised the possibility that genetic susceptibility to these environmental toxins may underlie ALS.

To look for genetic susceptibilities to ALS he has set up the Australian MND DNA Bank. He travels to all Australian mainland states collecting blood samples from people with ALS as well as controls. This Bank, supported by an NHMRC Enabling Grant, now contains over 1,400 DNA samples. Participants fill in detailed questionnaires to allow gene-environment studies to be undertaken. Using DNA from this Bank it has been shown that polymorphisms in the poliovirus receptor are more common in some forms of MND, and a variety of other genes that protect against toxins and viruses are under investigation.

Prof Pamphlett is now interested in novel genetic mechanisms that could underlie sporadic ALS, such as mutations that affect CNS cells predominantly (somatic mutations). To examine these possibilities he recruits ALS patients in NSW to donate their brains and spinal cords after they die to a Tissue Bank, and collaborates with other Banks in Australia and the UK to obtain further tissue samples.

Epidemiology. 2008 Mar; 19(2): 324-37.
Diet and amyotrophic lateral sclerosis.
Morozova N, Weisskopf MG, McCullough ML, Munger KL, Calle EE, Thun MJ, Ascherio A., Natalia Morozova; Marc G. Weisskopf; Marjorie L. McCullough; Kassandra L. Munger; Eugenia E. Calle; Michael J. Thun; Alberto Ascherio
Departments of *Nutrition, Harvard School of Public Health, Boston, MA 02215, USA. nmorozov@hsph.harvard.edu; mweissko@hsph.harvard.edu; marji.mccullough@cancer.org; hpklg@channing.harvard.edu; aascheri@hsph.harvard.edu; kgorham@hsph.harvard.edu; mthun@cancer.org; jcalle@cancer.org; ethacker@post.harvard.edu

BACKGROUND:
Several dietary factors have been associated with risk of amyotrophic lateral sclerosis (ALS) in case-control studies, but no prospective studies have investigated diet and ALS.

METHODS:
We prospectively assessed the association of selected foods and beverages with ALS mortality among participants of the Cancer Prevention Study II, a cohort of over 1 million men and women enrolled in 1982. Habitual diet was assessed with a 44-item food frequency questionnaire. Participant follow-up was conducted from 1989 through 2002 for ALS mortality.

RESULTS:
During the follow-up period, 862 cohort participants died of ALS. The strongest finding was an inverse association between chicken consumption and risk of ALS (P for trend = 0.0006). We also observed an increased risk of ALS among study participants with a high consumption of brown rice/whole wheat/barley (P for trend = 0.006) and decaffeinated coffee (P for trend = 0.01), and a decreased risk of ALS for high consumption of tea (P for trend = 0.02) and French fries (P for trend = 0.02); however, none of these latter associations remained significant after adjusting for multiple comparisons.

CONCLUSIONS:
Overall, these results do not provide convincing evidence that the investigated food items are related to ALS mortality. The association observed between chicken consumption and ALS mortality should be assessed in other studies. PMID: 18300717

South Med J. 2008 Sep; 101(9):969.
Overlooked aspartame-induced hypertension.
Roberts HJ.
PMID: 18708962

Overlooked Aspartame-Induced Hypertension

To the Editor: As a constructive comment on the excellent article by Trewet, C. L. and Ernst, 1 on "resistant hypertension", allow me to mention an important factor contributing to hypertension that continues to be overlooked: "diet" products containing aspartame which are being consumed by an estimated two-thirds of the population.

I reported earlier on hypertension in 64 aspartame reactors who were not known to have had an elevated blood pressure prior to using this chemical. 2

Its severity was impressive -- e.g., a registered nurse with readings as high as 280/160.

The blood pressure in another nurse rose to 240/150.

Several patients were studies to rule out pheochromocytoma.

The causative role of aspartame products was indicted by 1) the striking improvement or normalization of blood pressure after stopping aspartame, and 2) the prompt recurrence of hypertension following aspartame resumption.

The association of hypertension with the consumption of cola beverages (Diet Coke (TM)) has been confirmed by Winkelmayer et al in a large prospective study of female nurses -- but NOT with caffeine consumption. They speculated that "perhaps some other compound contained in soda-type soft drinks .... may be responsible for the increased risk of hypertension."

I have reviewed the likely pharmacologic basis, especially the conversion of phenylalanine (comprising half of the aspartame molecule) to dopamine, epinephrine, and norepinephrine ... all pressor substances. 2

Other aspartame reactors have evidenced peripheral vasomotor features (including the Raynaud phenomenon, 2 and probable pulmonary hypertension. 4

At the very least, persons with hypertension that resist conventional therapy ought to avoid aspartame products.

H. J. Roberts, MD, FACP, FCCP
Palm Beach Institute for Medical Research, Inc.
West Palm Beach, Florida

References

  1. Trewet CL, Ernest ME.
    Resistant hypertension; identifying causes and optimizing treatment regimens.
    South Med J 2008; 101: 166-173.

  2. Robert HJ.
    Aspartame Disease: An Ignored Epidemic
    West Palm Beach, Sunshine Sentinel Press, 2001.

  3. Winkelmayer WC, Stampfer MJ, Willett WC, et al.
    Habitual caffeine intake and the risk of hypertension in women.
    JAMA 2005; 294: 2330-2335.

  4. Roberts HJ.
    Aspartame induced dyspnea and pulmonary hypertension.
    Townsend Letter for Doctors and Patients 2003: 54-55.

Aspartame Induced Arrhythmias and Sudden Death, HJ Roberts 2004: Murray 2008.06.26
http://rmforall.blogspot.com/2008_06_01_archive.htm
Thursday, June 26, 2008
http://groups.yahoo.com/group/aspartameNM/message/1544

Aspartame Induced Arrhythmias and Sudden Death

By H. J. Roberts, M.D., F.A.C.P., F.C.C.P.
E-Mail: HJrobertsmd@aol.com
(c)2004 by H. J. Roberts, M.D.

A recent extensive review of sudden death in young athletes (1) made no mention of aspartame as a primary cause or suspected contributory factor, especially when demonstrable pathology was absent.

This issue has assumed great public health importance because "diet" products containing this chemical are being consumed by over two-thirds of the population -- especially weight-conscious persons.

I have repeatedly reported the serious cardiovascular, 'neuropsychiatric, metabolic and other adverse effects of aspartame products. (2-4)

Among the first 1200 aspartame reactors in my data base, 193 (16%) had symptomatic arrhythmia, 85 (7%) atypical chest pain, and 64 (5%) recent or aggravated hypertension.

One hypertensive patient developed complete heart block within hours after consuming his first diet cola.

Another had undergone unsuccessful radio frequency ablations in the heart before awareness of having aspartame disease.

Pheochromocytoma was suspected in several aspartame reactors.

The issue of sudden death related to aspartame and its breakdown products has been raised a number of times, particularly among previously well individuals using such products... including pilots and drivers, (3,4,6) and athletes.

I have detailed the release of norepinephrine, epinephrine, dopamine and free methanol by aspartame; a host of pertinent-related pathophysiologic conditions, (e.g., cumulative formaldehyde adducts derived from aspartame in tissue proteins and nucleic acids; excessive insulin release); direct oropharyngeal absorption from gum, breath fresheners and other products; and the increasing problem of aspartame addiction. (4-7)

The likelihood of pulmonary hypertension induced by the vasoconstrictive effects of aspartame products also has been considered. (5)

It is relevant that unexplained dyspnea was experienced by 110 aspartame reactors, usually with prompt improvement after abstinence.

Moreover, primary pulmonary hypertension was found at autopsy in a 27 year old female aspartame reactor.

The lack of familiarity of most physicians and medical examiners with the foregoing considerations can have serious legal consequences.

A case in point is that of a young woman (also a Sunday School teacher) who has been sentenced to serve 50 years in a Virginia prison for allegedly poisoning her husband with methyl alcohol. [Diane and Charles Fleming]

Elevated methanol blood concentrations were found postmortem in this body builder/basketball player who drank ten diet drinks and other aspartame products daily.

She remains incarcerated despite affidavits indicating that 10% of aspartame becomes free methyl alcohol after consumption.

The need for clinicians and corporate-neutral investigators to evaluate the contributory role of aspartame in cardiopulmonary disorders and sudden death, and drug interactions with aspartame, is underscored by the frequency of persons dying unexpectedly being categorized as "death due to causes yet to be determined."

One interested resident of Orange county (California) found 192 persons listed in this category between July 11 and November 15, 2003 according to the Orange county Register.

References:

Maron BJ
Sudden death in young athletes
N Engl J Med 2003; 349: 1064-1075.

Roberts HJ
Reactions to aspartame containing products: 551 cases
J Appl Nutr l988; 40: 86-94.

Roberts HJ
Aspartame (NutraSweet): Is It Safe?
Philadelphia, The Charles Press, 1989.

Roberts HJ
Aspartame Disease: An Ignored Epidemic.
West Palm Beach, Sunshine Sentinel Press, 2001.

Roberts HJ
Aspartame-induced dyspnea and pulmonary hypertension
Townsend Letter for Doctors & Patients 2003; 237 (January): 64-65.

Roberts HJ
Ignored Health Hazards for Pilots and Drivers.
West Palm Beach, Sunshine Sentinel Press, 1998.

Roberts HJ, Aspartame (NutraSweet) Addiction
Townsend Letter for Doctors & Patients, 2000; 198 (January): 52-57.

H. J. Roberts, MD, FACP, FCCP
Palm Beach Institute for Medical Research
P. O. Box 17799
West Palm Beach, Florida 33416 USA

Prev Med. 2008 Jul; 47(1): 136-9. Epub 2008 Apr 8.
Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina.
Andreatta MM, Muñoz SE, Lantieri MJ, Eynard AR, aeynard@cmefcm.uncor.edu; Navarro A. anavarro@cmefcm.uncor.edu; Escuela de Nutrición, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba.

OBJECTIVE:
To determine the role of the habitual use of the most common artificial sweeteners (AS) in the development of urinary tract tumors (UTT) in Argentina.

METHODS:
Case-control study of 197 patients with histologically confirmed UTT of transitional varieties, and 397 controls with acute, non-neoplastic, and non-urinary tract diseases, admitted to the same hospitals in Córdoba (Argentina) between 1999 and 2006.

All subjects were interviewed about their use of AS and their exposure to other known or suspected risk factors for UTT.

RESULTS:
Fifty-one UTT patients (26%) and 87 controls (22%) used AS.

The risk of UTT was significantly increased in long-term (>/=10 years) AS users compared with none-AS users.

The OR (95% CI) for long-term consumers was 2.18 (1.22-3.89) and for short-term users was 1.10 (0.61-2.00) after adjustment for age, gender, BMI, social status, and years of tobacco use.

CONCLUSION:
Regular use of AS for 10 years or more was positively associated with UTT. PMID: 18495230

Letter to the Editor
European Journal of Clinical Nutrition advance online publication 11 June 2008; doi: 10.1038/ejcn.2008.38
There really is no controversy
A Samuels, Solana Beach, CA, USA

Correspondence: A Samuels, E-mail: adieonly@aol.com;

It is noted in the excellent review by Humphries et al. (2008) that debate [over safety] still continues 20 years after the FDA had approved the use of aspartame.

Regarding that debate, the following comments are in order.

"Aspartame has never been shown to be safe for human consumption."

"Aspartame was discovered in 1965. Required safety testing began in 1967. >To date, no research outside of the aspartame industry has found aspartame to be safe for human consumption."

"In June 1979, the US Food and Drug Administration (FDA) established a Public Board of Inquiry (PBOI) to rule on aspartame safety issues. The PBOI concluded that NutraSweet/aspartame should not be approved pending further investigations of brain tumors in animals."

"In 1981, Ronald Reagan became President of the United States; Arthur Hull Hayes Jr was named FDA Commissioner; a Commissioner's panel was established to review issues raised by the PBOI; the panel advised against approval of aspartame; Hayes overruled the PBOI, ignored the recommendations of his own internal FDA team and approved aspartame for use in dry products."

"The so-called aspartame-industry 'science' is flawed to the point of being worthless."

"Controversy about the safety of aspartame is a device used by those who profit from production and sale of the product. Industry sponsored studies referring to brain damage draw conclusions without basis. Illustrating this practice is a 1980 study which reads, in part, "On the basis of blood absorption curves...[it] is concluded that (aspartame)...does not result in hypothalamic damage in the newborn monkey (Reynolds et al., 1980)."

"Using techniques similar to those of the glutamate industry (Samuels, 1999), the aspartame industry, in studies of adverse reactions, has manipulated subjects, procedures and statistics to enable researchers to draw the conclusion that there is no significant difference in reactions following ingestion of aspartame as opposed to ingestion of placebo. The study of Geha et al., 1993 illustrates the point."

"The FDA gives every appearance of cooperating with the aspartame industry in promoting the 'safety' of aspartame."

"Badly flawed industry sponsored studies have gone unchallenged."

"Following the unwarranted approval of aspartame, the FDA Adverse Reactions Monitoring System began receiving, and accepting, unsolicited reports of reactions to aspartame. A 26 June 1997 Memorandum from Technical Information Specialist (HFS-728) to Health Hazard Evaluation Board reported that the FDA has received 7259 complaints of adverse reactions attributed to the use of aspartame."

"The FDA has a history of minimizing the extent and severity of adverse reactions to food. Reports of debilitating or life-threatening reactions are not routinely investigated, and reports of 'death,' for example, are listed as 'other.'"

"In the late 1990s, the FDA stopped accepting reports of adverse reactions to aspartame."

In conclusion, Humphries et al., 2008 suggested that 'serious further testing and research be undertaken to eliminate any and all controversies surrounding this product'. It is suggested, rather, that with thoughtful analysis of the industry sponsored studies, it will become abundantly clear that no legitimate controversy about aspartame's toxic potential exists.

References

  1. Geha R, Buckley CE, Greenberger P, Patterson R, Polmar S, Saxon A et al. (1993).
    Aspartame is no more likely than placebo to cause urticaria/angioedema: results of a multicenter, randomized, double-blind, placebo-controlled, crossover study.
    J Allergy Clin Immunol 92, 513-520. Article PubMed ChemPort

  2. Humphries P, Pretorius E, Naude H (2008).
    Direct and indirect cellular effects of aspartame on the brain.
    Eur J Clin Nutr 62, 451-462. Article PubMed ChemPort

  3. Reynolds WA, Stegink LD, Filer Jr LJ, Renn E (1980).
    Aspartame administration to the infant monkey: hypothalamic morphology and plasma amino acid levels.
    Nat Rec 198, 73-85. ChemPort|

  4. Samuels A (1999). The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information.
    Account Res 6, 259-310. PubMed

Two aspartame toxicity research studies by Resia Pretorius
U. Pretoria, South Africa, debate with JD Fernstrom: Murray 2008.04.04
http://rmforall.blogspot.com/2008_04_01_archive.htm
Friday, April 4, 2008
http://groups.yahoo.com/group/aspartameNM/message/1536

Two detailed critiques of industry affiliations and biased science in 99 page review with 415 references by BA Magnuson, GA Burdock and 8 more, Critical Reviews in Toxicology, 2007 Sept.: Mark D Gold 13 page: also Rich Murray 2007.09.15: 2008.03.24
http://rmforall.blogspot.com/2008_03_01_archive.htm
Monday, March 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1531

http://www.truthinlabeling.org Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information. Accountability in Research 1999; 6: 259-310. 52-page review adandjack@aol.com; adieonly@aol.com

http://groups.yahoo.com/group/aspartameNM/message/857
http://www.dorway.com Original documents and long reviews of flaws in aspartame toxicity research: Murray 2002.07.31

http://groups.yahoo.com/group/aspartameNM/message/858
Samuels: Strong: Roberts: Gold: flaws in double-blind studies re aspartame and MSG toxicity: Murray 2002.08.01

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
Aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter: Murray 2000.07.10

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06

http://groups.yahoo.com/group/aspartameNM/message/928

Revolving door, Monsanto, FDA, EPA: NGIN: Murray 2002.12.23

http://www.nytimes.com/2008/02/05/health/nutrition/05symp.html?ref=health

Fitness & Science
Vital Signs

Symptoms: Metabolic Syndrome Is Tied to Diet Soda
By Nicholas Bakalar
Published February 5, 2008

Researchers have found a correlation between drinking diet soda and metabolic syndrome -- ­ the collection of risk factors for cardiovascular disease and diabetes that include abdominal obesity, high cholesterol and blood glucose levels, and elevated blood pressure.

The scientists gathered dietary information on more than 9,500 men and women ages 45 to 64 and tracked their health for nine years.

Over all, a Western dietary pattern ­-- high intakes of refined grains, fried foods and red meat -- was associated with an 18 percent increased risk for metabolic syndrome, while a "prudent" diet dominated by fruits, vegetables, fish and poultry correlated with neither an increased nor a decreased risk.

But the one-third who ate the most fried food increased their risk by 25 percent, compared with the one-third who ate the least, surprisingly, the risk of developing metabolic syndrome was 34 percent higher among those who drank one can of diet soda a day compared with those who drank none.

"This is interesting," said Lyn M. Steffen, an associate professor of epidemiology at the University of Minnesota and a co-author of the paper, which was posted online in the journal Circulation on Jan. 22. "Why is it happening? Is it some kind of chemical in the diet soda, or something about the behavior of diet soda drinkers?"

Copyright 2008 The New York Times Company

Circulation. 2008
Published online before print January 22, 2008, doi: 10.1161/CIRCULATIONAHA.107.716159
Submitted on May 18, 2007
Accepted on December 7, 2007

Dietary Intake and the Development of the Metabolic Syndrome.
The Atherosclerosis Risk in Communities Study
Pamela L. Lutsey MPH, lutsey@epi.umn.edu; Lyn M. Steffen PhD, MPH, RD*, steffen@epi.umn.edu; and June Stevens PhD, MS, RD june_stevens@unc.edu

From the Division of Epidemiology and Community Health, University of Minnesota, School of Public Health, Minneapolis (P.L.L., L.M.S.), and Department of Nutrition, University of North Carolina, Chapel Hill (J.S.).

Division of Epidemiology and Community Health
University of Minnesota
1300 South Second Street, Suite 300
Minneapolis, MN 55454, USA.
lutsey@epi.umn.edu

*To whom correspondence should be addressed.
E-mail: steffen@epi.umn.edu;

Background
The role of diet in the origin of metabolic syndrome (MetSyn) is not well understood; thus, we sought to evaluate the relationship between incident MetSyn and dietary intake using prospective data from 9514 participants (age, 45 to 64 years) enrolled in the Atherosclerosis Risk in Communities (ARIC) study.

Methods and Results
Dietary intake was assessed at baseline via a 66-item food frequency questionnaire.

We used principal-components analysis to derive "Western" and "prudent" dietary patterns from 32 food groups and evaluated 10 food groups used in previous studies of the ARIC cohort.

MetSyn was defined by American Heart Association guidelines.

Proportional-hazards regression was used.

Over 9 years of follow-up, 3782 incident cases of MetSyn were identified.

After adjustment for demographic factors, smoking, physical activity, and energy intake, consumption of a Western dietary pattern (Ptrend = 0.03) was adversely associated with incident MetSyn.

After further adjustment for intake of meat, dairy, fruits and vegetables, refined grains, and whole grains, analysis of individual food groups revealed that meat (Ptrend under 0.001), fried foods (Ptrend = 0.02), and diet soda (Ptrend under 0.001) also were adversely associated with incident MetSyn, whereas dairy consumption (Ptrend = 0.006) was beneficial.

No associations were observed between incident MetSyn and a prudent dietary pattern or intakes of whole grains, refined grains, fruits and vegetables, nuts, coffee, or sweetened beverages.

Conclusions
These prospective findings suggest that consumption of a Western dietary pattern, meat, and fried foods promotes the incidence of MetSyn, whereas dairy consumption provides some protection.

The diet soda association was not hypothesized and deserves further study. PMID: 18212291

Key words: dairy products, diet, food habits, meat, metabolic syndrome X

http://www.sph.unc.edu/?option=com_profiles&profileAction=ProfDetail&profileId=1277

June Stevens, PhD
Website: http://myprofile.cos.com/stevensh31
Email: june_stevens@unc.edu
Phone: 919-966-7218 Fax: 919-962-3265
University of North Carolina at Chapel Hill
School of Public Health
137 E Franklin St., Ste 400, CB#7461
Chapel Hill, NC 27514

Summary of Research Interests
AICR/WCRF Distinguished Professor and Chair
Department of Nutrition
Professor, Department of Epidemiology
(PhD in Human Nutrition, Cornell
1986, MS, Penn State, 1980)
Dr. Stevens is a nutrition epidemiologist with a large research program focusing on the causes, consequences, and prevention of obesity and different populations. She has special interests in minority health, anthropometry, and physical activity. Through her work at the Collaborative Studies Coordinating Center, she has access to obesity-related information from several large, multi-center studies. She is the Principal Investigator of the Coordinating Center for two national trials that examine obesity and physical activity in children and adolescents. Dr. Stevens is a member of the American Society for Nutritional Sciences, the American Heart Association Council on Epidemiology, the North American Society for the Study of Obesity, the International Association for the Study of Obesity (IASO) and the Society for Epidemiologic Research. Dr. Stevens is currently Vice President for Scientific Affairs of the IASO. She serves as a reviewer for the New England Journal of Medicine, the Journal of the American Medical Association, and the American Journal of Epidemiology, Obesity Research, and the International Journal of Obesity as well as several other journals.

Educational Background
1986 Cornell University PhD
Human Nutrition, Minor Statistics
1978 Pennsylvania State University MS
Human Nutrition
1975 Cleveland Metropolitan General Hospital RD
Clinical Dietetics

Barry M. Popkin , Professor of Nutrition
Carolina Population Center
University of North Carolina
123 West Franklin Street, Chapel Hill, NC 27516-3997
E-mail: popkin@unc.edu

Kiyah J Duffey E-mail: kduffey@unc.edu
>Address: 123 W. Franklin St., CPC, University Square
CB: 8120
Telephone: (919) 966-1735
Class: Graduate Doctorate
College: School Of Public Health
Degree: Doctor Of Philosophy
Department: Nutrition (4660)
Title: Research Assistant
Department: Nutrition (4660)
Home Address: 105 Fidelity St, B10, Carrboro, NC 275102617

http://www.blackwell-synergy.com/action/showFullText?submitFullText=Full+Text+HTML&doi=\10.1111%2Fj.1742-7843.2007.00200.x

Basic & Clinical Pharmacology & Toxicology
Volume 102 Issue 2 Page 118-124, February 2008

To cite this article:
Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, Laura Falcioni, Luciano Bua (2008)
Consequences of Exposure to Carcinogens
Beginning During Developmental Life
Basic & Clinical Pharmacology & Toxicology 102 (2), 118-124.
doi:10.1111/j.1742-7843.2007.00200.x

Consequences of Exposure to Carcinogens
Beginning During Developmental Life
Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, Laura Falcioni and Luciano Bua
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology and Environmental Sciences, Bologna, Italy

Author for correspondence: Morando Soffritti
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology and Environmental Sciences, Castello di Bentivoglio, Via Saliceto 3, 40010 Bentivoglio, Bologna, Italy
fax +39 051 6640223, e-mail crcfr@ramazzini.it

Abstract:

The increased incidence of cancer over the last 50-60 years may be largely attributed to two factors: the ageing of the population and the diffusion of agents and situations presenting carcinogenic risks.

Today, we have entered into a new era in which populations are ever-increasingly exposed to diffuse carcinogenic risks, present not only in the occupational, but also in the general environment.

We must now also consider an additional factor in the carcinogenic process, that is, the age in which exposure to carcinogenic risks begins.

Apart from the paradigmatic cases of diethylstilboestrol and ionizing radiation, the available epidemiological data concerning the adult consequences of developmental exposure to carcinogens is very limited.

However, important data have been provided by long-term experimental carcinogenicity bioassays conducted using rodents.

This paper reports a selection of studies conducted in the laboratories of the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation in which exposure to the chemical agents vinyl acetate monomer, ethyl alcohol and aspartame was started during developmental life and continued into adulthood.

The results of these studies provide supporting evidence that lifespan exposure to carcinogenic agents beginning during developmental life produces an overall increase in the carcinogenic effects observed.

Moreover, when comparing prenatal and postnatal exposure, the data demonstrate that the development of cancers may appear earlier in life.

Cancer represents one of the most important issues in public health today, both in the industrialized and developing worlds.

The epidemiological dimension of the disease is epidemic, with one out of two males and one out of three females destined to become ill with cancer during their lifetimes [1].

Above all, cancer affects the oldest segment of the population, from 60-84 years of age.

Data from the Nominative Mortality Register of European Ramazzini Foundation from the period 1982-2002 show that more than 30% of the mortality in the province of Bologna, Italy, is cancer-related.

Of these deaths, 80% occurred after the age of 60-65 years [2].

If we consider the estimates that in 25 years, the number of persons over than the age of 70 years will have doubled, it is necessary to prepare for a dramatic increase in the number of tumours.

In the USA alone, it is predicted that the number of cancers will indeed double by 2050 [1].

Although the scientific effort and economic resources dedicated to cancer have increased over the last 30 years (directed especially towards the discovery of effective cancer drug therapies), in the USA, the 5-year relative survival rates based on patient follow-up from 1976-2000 have not substantially improved (table 1), with the exception of female breast, prostate and colon-rectal cancer, for which early diagnosis has certainly played an important role.

Other exceptions are cancers of the lung and bronchus in males that reflects the decrease in smoking more than the past 30 years.

The increased incidence of cancer over the last 50-60 years may be attributed to two increasing trends: (i) the increase in life expectancy (about 10 years for males and 15 years for females); and (ii) the increase in the diffusion of agents and situations presenting carcinogenic risks in both the occupational and general environment. A third factor in the carcinogenetic process is genetic predisposition; however, it is unlikely that this factor has changed significantly over the last decades.

In addition, a fourth factor must also be considered; that is, the age in which exposure to carcinogenic risks begins.

In this context, the present epidemiological dimension of cancer is undoubtedly a sign of the previous era in which the majority of the population had been exposed to carcinogenic risks either in the occupational environment as adolescents or adults.

Today, however, we are facing an era characterized by two new trends: (i) lifetime exposure to carcinogenic risks beginning during developmental life (prenatally or postnatally).

This exposure during early development, when cell mutiplication and differentiation make an organism more vulnerable, may cause an increase in carcinogenic effects later in life; and (ii) exposure to 'diffuse carcinogenic risks'. This term is used to describe carcinogenic risks of low potency, but to which almost the entire population of the planet may be exposed.

Examples of diffuse carcinogenic risks include: (i) agents that are slightly carcinogenic at any dose; (ii) low or extremely low doses of strong carcinogenic agents; or (iii) mixtures of small doses of any carcinogenic agent [3].

Apart from the paradigmatic cases of diethylstilboestrol and ionizing radiation, the available epidemiological data concerning the adult consequences of developmental exposure to carcinogenic agents are very limited.

We now know much more about the effects of this early exposure thanks to experimental long-term bioassays.

If adequately designed and conducted, these bioassays can produce data that can be effectively used to identify/predict carcinogenic risks and, consequently, to make decisions to protect public health.

Numerous long-term carcinogenicity studies have been conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF) that demonstrate the life-time consequences of chemical/physical exposures beginning during developmental life and lasting for life.

This paper presents a selection of these exemplary cases including vinyl acetate, ethyl alcohol and aspartame.

The case of vinyl acetate monomer

Vinyl acetate monomer is an important compound used in the plastics industry.

It is also used in the production of resin in chewing gum.

The limited available epidemiological data on vinyl acetate monomer do not allow for an evaluation of its potential carcinogenic risks in human beings.

Carcinogenicity studies on rats and mice, conducted prior to the most recent International Agency for Research on Cancer evaluation [4], have been in one way or another inadequate to evaluate the carcinogenic potential of vinyl acetate monomer.

In the 1980s, a series of experiments were simultaneously conducted at the CMCRC/ERF using Sprague-Dawley rats, Wistar rats and Swiss mice.

A similar protocol was applied for all three experiments.

Vinyl acetate monomer was administered by ingestion in drinking water supplied ad libitum at the concentrations of 5000, 1000 or 0 p.p.m. to 17-week-old males and females (breeders) and 12-day-old embryos (offspring).

The treatment lasted 104 weeks in rats and 78 weeks in mice.

All animals were monitored until natural death (130-150 weeks).

The plan of each experiment and the significant carcinogenic results are reported in tables 2-4.

In the tested conditions, vinyl acetate monomer was demonstrated to be a multipotent carcinogenic agent, inducing malignant tumours of the oral cavity, tongue, oesophagus and forestomach in both strains of rats and mice.

A slight increase of the incidence of adenomas/carcinomas of the lung and of malignant tumours of the uterus in mice was also observed [5-7].

Furthermore, the carcinogenic effects were strongly increased when exposure began during foetal life.

The case of ethyl alcohol

Various epidemiological studies have shown a positive relationship between consumption of alcoholic beverages and the increase of cancer risks of the oral cavity, pharynx, larynx, oesophagus and liver.

However, as reported in the most recent International Agency for Research on Cancer monograph on this agent [8], many experimental studies conducted on rats and mice exposed to various concentrations of ethyl alcohol administered in drinking water did not show the same effects.

In an experiment performed at the CMCRC/ERF laboratories, ethyl alcohol was administered by ingestion in drinking water at the concentration of 10% or 0% and supplied ad libitum to male and female Sprague-Dawley rats, both breeders and offspring.

In order to detect carcinogenic risk when exposure begins during adult life, treatment of breeders started at 39 weeks of age, 7 days before mating.

Treatment of offspring began during embryonic life.

Treatment of all rodents lasted for 104 weeks and all animals were observed until spontaneous death.

The plan of the experiment and the significant carcinogenic results are reported in table 5.

In contrast with previous studies, in the test conditions of the CMCRC ethyl alcohol was indeed demonstrated to be carcinogenic for various organs and tissues, in particular inducing malignant tumours of oral cavity, tongue and lips, and oesophagus, the same sites that were shown to be target organs in the aforementioned epidemiological studies [9].

Importantly, the incidence of malignant tumours of the oral cavity was higher when exposure began during embryonic life.

The case of aspartame

Aspartame is an artificial sweetener consumed by hundreds of millions of people worldwide.

It is used in over 6000 products, including soft drinks, chewing gum, candy, desserts and yogurt, as well as in more than 500 pharmaceutical products, in particular, syrups and antibiotics for children.

Prior to the commercialization of aspartame in the 1970s, the manufacturers of the compound conducted various experimental studies on rats and mice to test its carcinogenicity.

When taken together, the results of these studies were considered negative with regard to the carcinogenicity of aspartame.

Doubts were, however, raised by some in the scientific community about the conduct of the experiments and the fact that some cases of malignant brain tumours were found among animals treated with aspartame while none were found among the control group.

Given the limitations of these studies due to the number of animals per sex and group, the duration of the experiment, and the ever growing use of aspartame throughout the years, the CMCRC/ERF decided in the late 1990s to plan and perform an experiment that would provide an adequate evaluation of the potential carcinogenic effects of aspartame.

The first CMCRC/ERF study [10-12] was conducted on 1800 Sprague-Dawley rats (100-150/per sex/per group).

Aspartame was added to the standard rat diet in quantities of 100,000; 50,000; 10,000; 2000; 400; 80 or 0 p.p.m. in order to simulate daily intake of 5000, 2500, 500, 100, 20, 4 or 0 mg/kg of body weight.

Treatment of the animals began at 8 weeks of age and continued until spontaneous death.

The results, reported in table 6, show that aspartame causes a significant, dose-related increase of lymphomas/leukaemias and malignant tumours of the renal pelvis and ureter in females and malignant tumours of peripheral nerves in males.

These results demonstrate for the first time that aspartame is a carcinogenic agent, capable of inducing malignancies at various dose levels, including those lower than the current acceptable daily intake for humans (50 mg/kg of body weight in the USA, 40 mg/kg of body weight in the European Union).

As soon as we perceived the carcinogenic effects of aspartame during the elaboration of the data in our first mega-experiment, we planned an integrated programme of long-term bioassays, beginning treatment from prenatal life, on an additional 1500 rats and mice in order to better quantify the carcinogenic risks of aspartame.

The second CMCRC/ERRF study [13] was conducted o 400 Sprague-Dawley rats (70-95/per sex/per group).

Aspartame was added to the standard rat diet in quantities of 2000, 400 or 0 p.p.m. in order to simulate daily intake of 100, 20 and 0 mg/kg of body weight.

Treatment of the animals began on the 12th day of foetal life and lasted until natural death.

The results of the second study show an increased incidence of lymphomas/leukaemias in female rats with respect to the first study.

Moreover, the study shows that when lifespan exposure to aspartame begins during foetal life, the age at which lymphomas/leukaemias develop in females is anticipated (fig. 1).

In addition, for the first time, a significant increase in mammary cancers in females was also observed.

The results of this second study confirm the first experimental demonstration of aspartame's multipotential carcinogenicity and demonstrate that developmental exposure aggravates the carcinogenic effects (tables 7 and 8).

Conclusions

It is well known that the latency time of most cancers (i.e. the time elapsing between the start of exposure to carcinogenic risks and the clinical manifestation of cancers) may span from 20 to 40 years [14].

In light of the fact that 80% of cancers are diagnosed over the age of 55-60 years, we may attribute the present epidemiological dimension of cancer to exposure beginning during adolescence or adulthood.

Nowadays, we are facing a new era in which exposure to carcinogenic risks begins during developmental life (prenatal and postnatal) and continues into adulthood.

Based on the results of long-term carcinogenicity bio-assays testing chemical and physical agents using rodents, there is ample evidence demonstrating that developmental, in conjunction with adult exposure to carcinogenic risks, produces an overall increase in the incidence of malignant tumours and an increased incidence of specific neoplasms related to exposures to specific carcinogens.

Moreover, when comparing prenatal and postnatal exposure, the development of certain tumours may appear earlier in life.

We must take into serious consideration the warnings provided by long-term carcinogenicity studies and take adequate action today.

Based on the evidence presented, increased attention must be given to developmental exposures to diffuse carcinogens.

It is only in this way that in the future we can hope to avoid a passive registration of a worsening epidemiological situation.

References

  1. American Cancer Society. Cancer Statistics 2006.
    Available from: http://www.cancer.org. Accessed 28 May 2007.
  2. Soffritti M, Vrahulaki C, Belpoggi F et al.
    Resoconti del registro tumori di Bologna e provincia 1982-2002.
    Eur J Oncol; in press.
  3. Soffritti M, Belpoggi F, Minardi F, Bua L, Maltoni C.
    Megaexperiments to identify and assess diffuse carcinogenic risks.
    Ann N Y Acad Sci 1999; 895: 34-55.
    Synergy, Medline, ISI, Chemport, CSA
  4. International Agency for Research on Cancer.
    IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Wood Dust and Formaldehyde, vol. 62. IARC, Lyon, France, 1995.
  5. Minardi F, Belpoggi F, Soffritti M et al.
    Results of long-term carcinogenicity bioassay on vinyl acetate monomer in Sprague-Dawley rats.
    Ann N Y Acad Sci 2002; 982: 106-22.
    Synergy, Medline, ISI, Chemport, CSA
  6. Belpoggi F, Soffritti M, Minardi F et al.
    Results of a long-term carcinogenicity bioassay on vinyl acetate monomer in Wistar rats.
    Eur J Oncol 2002; 7: 279-93.
  7. Maltoni C, Ciliberti A, Lefemine G, Soffritti M.
    Results of a long-term experimental study on the carcinogenicity of vinyl acetate monomer in mice.
    Ann N Y Acad Sci 1997; 837: 209-38.
    Synergy, Medline, ISI, Chemport, CSA
  8. International Agency for Research on Cancer.
    IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Alcohol Drinking, vol. 44. IARC, Lyon, France, 1998.
  9. Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
    Results of long-term experimental studies on the carcinogenicity of methyl alcohol and ethyl alcohol in rats.
    Ann N Y Acad Sci 2002;982:46-69.
    Synergy, Medline, ISI, Chemport, CSA
  10. Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L.
    Aspartame induces lymphomas and leukaemias in rats.
    Eur J Oncol 2005; 10: 107-16.
  11. Belpoggi F, Soffritti M, Padovani M, Degli Esposti D, Lauriola M, Minardi F.
    Results of long term carcinogenicity bioassay on Sprague-Dawley rats exposed to aspartame administered in feed.
    Ann N Y Acad Sci 2006; 1076: 559-77.
    Synergy, Medline, ISI, Chemport
  12. Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A.
    First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley Rats.
    Environ Health Perspect 2006; 114: 379-85.
    Medline, ISI, Chemport
  13. Soffritti M, Belpoggi F, Degli Esposti D, Tibaldi E, Lauriola M.
    Lifespan exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats.
    Environ Health Perspect 2007; 115: 1293-7.
    Medline, ISI, Chemport
    Owen WG.
    Diffuse mesothelioma and exposure to asbestos dust in the merseyside area.
    Br Med J 1964; 2: 214-8.
    Medline, Chemport

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Avoiding formaldehyde allergic reactions in children, aspartame, vitamins, shampoo, conditioners, hair gel, baby wipes, Sharon E Jacob, MD, Tace Steele, U. Miami, Pediatric Annals 2007 Jan.: eye contact dermatitis, AM Hill, DV Belsito, 2003 Nov.: Murray 2008.03.27
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Formaldehyde from many sources, including aspartame, is major cause of Allergic Contact Dermatitis, SE Jacob, T Steele, G Rodriguez, Skin and Aging 2005 Dec.: Murray 2008.03.27
http://rmforall.blogspot.com/2008_03_01_archive.htm
Thursday, March 27, 2008
http://groups.yahoo.com/group/aspartameNM/message/1533

Detailed critiques of JE Garst folic acid proposals by experts HJ Roberts and M Alemany: Murray 2008.03.20
http://rmforall.blogspot.com/2008_02_01_archive.htm
Thursday, March 20, 2008
http://groups.yahoo.com/group/aspartameNM/message/1530

RE: 5 mg folic acid helps methanol to not form toxic formaldehyde and formic acid -- no effect re formaldehyde from methanol in human breast and arterial epithelial tissue: Garth: Monte 2008.03.19
http://rmforall.blogspot.com/2008_02_01_archive.htm
Wednesday, March 19, 2008
http://groups.yahoo.com/group/aspartameNM/message/1529

I disagree.

Methanol can not be "stopped" from conversion into formaldehyde by folic acid... no matter how high the dosage.

It is dangerous and misleading to even suggest this (see attached diagram).

Much has been written suggesting that folic acid deficiency "might" slow the conversion of "formate" to carbon dioxide and therefore induce a buildup of formaldehyde.

In the liver which has high concentrations of the various ADH enzymes this may be the case.

However, this would have little value in an organ such as the human breast where Class I ADH exists in high concentration with little or no Class 3 ADH (aldehyde dehydrogenase which requires folic acid).

In the human breast formate supplementation would have no effect in preventing methanol conversion to formaldehyde.

The production of formaldehyde in the liver has never been my concern ... I have always feared that the real harm done from methanol was caused by its conversion in the breast and arterial epithelial tissue, as we find in the brain and elsewhere.

There is some serious concern that folic acid in the form that it is found in commercial supplementation can actually cause more harm than good.

I will always suggest that any folic acid be supplemented from natural sources, and not pharmaceutical.

The methanol literature is rich and worthy of study.

Woody Monte

5 mg folic acid helps methanol to not form toxic formaldehyde and formic acid, but most research has neglected folic acid deficiency re cancer, birth defects, and neurotoxicity -- flaws in many studies on aspartame -- breakthrough insights by John E Garst, PhD toxicologist: Murray 2008.03.19
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Sunday, February 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1524

New details on how formaldehyde and formic acid from methanol are neurotoxic: Chun Lai Nie, Rong Giao He, et al, PLoS ONE 2(7): e629 2007.07.18 Chinese Academy of Sciences, Beijing: Murray 2007.09.01
http://groups.yahoo.com/group/aspartameNM/message/1470

"Recent studies have shown that neurodegeneration is closely related to misfolding and aggregation of neuronal tau."

"The significant protein tau aggregation induced by formaldehyde and the severe toxicity of the aggregated tau to neural cells may suggest that toxicity of methanol and formaldehyde ingestion is related to tau misfolding and aggregation."

"Neuronal tau is an important protein in promoting and stabilizing the microtubule system involved in cellular transport and neuronal morphogenesis."

"Both formaldehyde and acetaldehyde can go through the blood-brain barrier and cause some lesions to CNS, especially our visual system [38].

Clinically, the lethal dose of formaldehyde for human beings is about 0.08% in the circulation [39].

We have shown in the present study that formaldehyde can significantly induce tau aggregation and polymerization at concentrations even lower than 0.08%, the clinical dose of toxicosis."

"Formaldehyde exposure leads to formation of DNA/protein crosslinks, a major mechanism of DNA damage.

The DNA/protein crosslinks have been used as a measure of dose in drug delivery [20].

Formaldehyde, as a crosslinking agent, also reacts with thiol and amino groups, leading to protein polymerization [21], [22].

Furthermore, methanol ingestion is an important public health concern because of the selective actions of its toxic metabolites, formaldehyde and formic acid, on the retina, the optic nerves and the central nervous system (CNS) [23].

Illicit consumption of industrial methylated spirits can cause severe and even fatal illness [24].

In the liver and retina, methanol is oxidized by alcohol dehydrogenase, resulting in formaldehyde.

In semicarbazide-sensitive amine oxidase (SSAO)-mediated pathogenesis of Alzheimer's disease, formaldehyde interacts with B-amyloids and produces irreversibly cross-linked neurotoxic amyloid-like complexes [21], [22], [25].

We have examined the role of formaldehyde in misfolding of protein tau [26].

In particular, we investigated the toxicity of formaldehyde-induced tau aggregates on human neuroblastoma cells (SH-SY5Y cell line) and rat hippocampal cells [27].

The results showed that low concentrations (0.01 - 0.1%) of formaldehyde are sufficient to induce formation of amyloid-like tau aggregates, which can induce apoptosis of both SH-SY5Y and hippocampal cells.

This may be significant to understand the mechanism of chronic damage caused by methanol toxicity and formaldehyde stress [18], [28].

However, we have still not known the mechanism of protein tau aggregation in the presence of formaldehyde at low concentrations.

The present study concerns the characteristic of misfolding and polymerization of extracellular and intracellular neuronal tau induced by formaldehyde at low concentrations."

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1763784\4

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000629

Formaldehyde at Low Concentration Induces Protein Tau into Globular Amyloid-Like Aggregates In Vitro and In Vivo PLoS ONE. 2007 Jul 18; 2(7): e629.
doi:10.1371/journal.pone.0000629
Chun Lai Nie 1, Yan Wei 1, Xinyong Chen 2, Yan Ying Liu 1, Wen Dui 1, Ying Liu 1, Martyn C. Davies 2, Martyn.Davies@nottingham.ac.uk; Saul J.B. Tendler 2, Saul.Tendler@nottingham.ac.uk; Rong Giao He 1* herq@sun5.ibp.ac.cn

  1. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Graduate School, Chinese Academy of Sciences, Chaoyang District, Beijing, China

  2. Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, United Kingdom

Received: March 5, 2007; Accepted: June 13, 2007
Published: July 18, 2007

Copyright: Â(c) 2007 Nie et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

*To whom correspondence should be addressed.
E-mail: herq@sun5.ibp.ac.cn

Abstract

Recent studies have shown that neurodegeneration is closely related to misfolding and aggregation of neuronal tau.

Our previous results show that neuronal tau aggregates in formaldehyde solution and that aggregated tau induces apoptosis of SH-SY5Y and hippocampal cells.

In the present study, based on atomic force microscopy (AFM) observation, we have found that formaldehyde at low concentrations induces tau polymerization whilst acetaldehyde does not.

Neuronal tau misfolds and aggregates into globular-like polymers in 0.01 - 0.1% formaldehyde solutions.

Apart from globular-like aggregation, no fibril-like polymerization was observed when the protein was incubated with formaldehyde for 15 days.

SDS-PAGE results also exhibit tau polymerizing in the presence of formaldehyde.

Under the same experimental conditions, polymerization of bovine serum albumin (BSA) or a-synuclein was not markedly detected.

Kinetic study shows that tau significantly misfolds and polymerizes in 60 minutes in 0.1% formaldehyde solution.

However, presence of 10% methanol prevents protein tau from polymerization.

This suggests that formaldehyde polymerization is involved in tau aggregation.

Such aggregation process is probably linked to the tau's special "worm-like" structure, which leaves the e-amino groups of Lys and thiol groups of Cys exposed to the exterior.

Such a structure can easily bond to formaldehyde molecules in vitro and in vivo. Polymerizing of formaldehyde itself results in aggregation of protein tau.

Immunocytochemistry and thioflavin S staining of both endogenous and exogenous tau in the presence of formaldehyde at low concentrations in the cell culture have shown that formaldehyde can induce tau into amyloid-like aggregates in vivo during apoptosis.

The significant protein tau aggregation induced by formaldehyde and the severe toxicity of the aggregated tau to neural cells may suggest that toxicity of methanol and formaldehyde ingestion is related to tau misfolding and aggregation.

Funding: This project was supported by NSFB (06J11), the NSFC (Nos. 90206041, 30570536 and 30621004) and 973-Project (2006CB500703 and 2006CB911003).

Competing interests: The authors have declared that no competing interests exist.

Academic Editor: Christophe Herman, Baylor College of Medicine, United States of America

MSG and Aspartame -- A Personal Story, TV health reporter Dick Allgire (vegetarian) healed of migraines and panic attacks: Murray 2008.02.12
http://rmforall.blogspot.com/2008_02_01_archive.htm
Tuesday, February 12, 2008
http://groups.yahoo.com/group/aspartameNM/message/1520

Subjective symptoms of medical students exposed to formaldehyde during a gross anatomy dissection course, Wei CN et al, Center for Policy Studies, Kumamoto University, Japan, Int J Immunopathol Pharmacol. 2007 Apr. Murray 2008.02.12
http://rmforall.blogspot.com/2008_02_01_archive.htm
Tuesday, February 12, 2008
http://groups.yahoo.com/group/aspartameNM/message/1519

1 ppm formaldehyde in air = 1.23 mg/cubic meter, so breathing 20 cubic meters, living in mobile homes, would retain about 20 mg formaldehyde daily, ten times the 1999 EPA alarm level for daily drinking water.

Old tiger roars -- Woodrow C Monte, PhD -- aspartame causes many breast cancers, as ADH enzyme in breasts makes methanol from diet soda into carcinogenic formaldehyde -- same in dark wines and liquors, Fitness Life 2008 Jan.: Murray 2008.02.11
http://rmforall.blogspot.com/2008_02_01_archive.htm
Monday, February 11, 2008
http://groups.yahoo.com/group/aspartameNM/message/1517

Metabolic syndrome is tied to diet soda, PL Lutsey, LM Steffen, J Stevens, Circulation 2008.01.22: role of formaldehyde and formic acid from methanol in wines, liquors, or aspartame?: Murray 2008.02.07
http://rmforall.blogspot.com/2008_02_01_archive.htm
Thursday, February 7, 2008
http://groups.yahoo.com/group/aspartameNM/message/1513

Formaldehyde in FEMA trailers and other sources (aspartame, dark wines and liquors, tobacco smoke): Murray 2008.01.30
http://rmforall.blogspot.com/2008_01_01_archive.htm
Wednesday, January 30, 2008
http://groups.yahoo.com/group/aspartameNM/message/1508

Devra Lee Davis, U. Pittsburgh Cancer Institute, rejects aspartame -- Luke Ravenstahl, Mayor, drinks 12 cans Diet Pepsi daily: accurate warning by Ronald K. Frazer: Murray 2008.01.13
http://rmforall.blogspot.com/2008_01_01_archive.htm
Sunday, January 13, 2008
http://groups.yahoo.com/group/aspartameNM/message/1503

Seizures and hyponatremia after excessive intake of diet coke, LJ Mortelmans, M Van Loo, HG De Cauwer, K Merlevede, Klina General Hospital, Brasschaat, Belgium, EJEM 2008 Feb: Mark D. Gold critique: Murray 2008.01.10
http://rmforall.blogspot.com/2008_01_01_archive.htm
Thursday, January 10, 2008
>a href="http://groups.yahoo.com/group/aspartameNM/message/1502">http://groups.yahoo.com/group/aspartameNM/message/1502

Methyl alcohol ingestion as a model etiologic agent in multiple sclerosis, WC Monte, D Glanzman, C Johnston; Methanol induced neuropathology in the mammalian central nervous system, Woodrow C. Monte, Renee Ann Zeising, both reports 1989.12.04: Murray 2007.12.28
http://rmforall.blogspot.com/2007_12_01_archive.htm
Friday, December 28 2007
http://groups.yahoo.com/group/aspartameNM/message/1499

[These seminal 1989 studies by Prof. Woodrow C. Monte are also given in this previous post, along his two recent comprehensive reviews:

Role of formaldehyde, made by body from methanol from foods and aspartame, in steep increases in fetal alcohol syndrome, autism, multiple sclerosis, lupus, teen suicide, breast cancer, Nutrition Prof. Woodrow C. Monte, retired, Arizona State U., two reviews, 190 references supplied, Fitness Life, New Zealand 2007 Nov, Dec: Murray 2007.12.26
http://rmforall.blogspot.com/2007_12_01_archive.htm
Wednesday, December 26 2007
http://groups.yahoo.com/group/aspartameNM/message/1498]

Explosion in numbers of children with serious food allergies has bewildered experts and parents, Helen Francombe, The Australian 2007.11.17: role of formic acid from methanol in liquors and aspartame, Murray 2007.11.28
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 28, 2007
http://groups.yahoo.com/group/aspartameNM/message/1496

Folic acid prevents neurotoxicity from formic acid, made by body from methanol impurity in alcohol drinks [ also 11 % of aspartame ], BM Bhushan, PL Carlen, DC Lehotay, AC Vandenbroucke, Y Adamchik, U. of Toronto, 2007 Dec., Alcoholism Cl. Exp. Res.: Murray 2007.11.27
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 27, 2007
http://groups.yahoo.com/group/aspartameNM/message/1495

Comet assay tests groups of 4 mice to show sucralose genotoxicity in stomach, colon, lung, Yu F Sasaki et al, Mutation Research 2002, full plain text: more re aspartame and stevia: Murray 2007.11.25
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Industry scientists praise aspartame saffety and benefits in Paris on 2006.05.30, Herve Nordmann, Andrew G. Renwick, Carlo La Vecchia, Tommy Visscher, Jaap Seidell, France Bellisle, Adam Drewnowski, Margaret Ashwell, Anne de la Hunty, Sigrid A. Gibson, Alan R. Boobis: Murray 2007.11.18
http://groups.yahoo.com/group/aspartameNM/message/1491

Details on 6 epidemiological studies since 2004 on diet soda (mainly aspartame) correlations, as well as 13 other mainstream studies on aspartame toxicity since summer 2005: Murray 2007.11.14
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 14, 2007
http://groups.yahoo.com/group/aspartameNM/message/1490

Interstitial cystitis symptoms worse for coffee, tea, soda, alcoholic beverages, citrus fruits and juices, hot pepper, artificial sweeteners (not sucralose), B Shorter et al, Long Island U., J. Uriology 2007 July: Murray 2007.11.13
http://groups.yahoo.com/group/aspartameNM/message/1489

"The most frequently reported and most bothersome comestibles were coffee, tea, soda, alcoholic beverages, citrus fruits and juices, artificial sweeteners and hot pepper."

Aspartame decreases evoked extracellular dopamine levels in the rat brain, Brian P Bergstrom, Muskingum College, Neuropharmacology 2007.09.29: Murray 2007.11.06
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"These findings suggest that APM has a relatively potent effect of decreasing evoked extracellular DA levels when administered systemically under the conditions specified."

Diet soda consumption was not associated with any surrogate measures of insulin resistance after adjustment for potential confounders, M Yoshida et al, Nutritional Epidemiology Program, Tufts U., J. Nutrition 2007 Sept.: Murray 2007.10.31
http://groups.yahoo.com/group/aspartameNM/message/1484

"Diet soda consumption was not associated with any surrogate measures of insulin resistance after adjustment for potential confounders ..."

13,620 seniors using more than 1 can/week artificially sweetened [aspartame] soft drinks had 8% higher death risk, 1981-2004, Paganini-Hill A, Kawas CH, Corrada MM, U. Southern Cal., Prev. Med. 2007 April 44(4) 305-10: Murray 2007.10.12
http://RMForAll.blogspot.com October 12, 2007
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"Individuals who drank more than 1 can/week of artificially sweetened (but not sugar-sweetened) soft drink (cola and other) had an 8 % increased risk (95 % CI: 1.01-1.16)."

"The increased death risk with consumption of artificially sweetened, but not sugar-sweetened, soft drinks suggests an effect of the sweetener rather than other components of the soft drinks, although residual confounding remains a possibility."

About second Ramazzini cancer rat study, M. Nathaniel Mead: Morando Soffritti: Murray 2007.10.09
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http://www.ehponline.org/docs/2007/115-9/EHP115pa460PDF.PDF
http://www.ehponline.org/docs/2007/115-9/ss.html#aspa

Environmental Health Perspectives Volume 115, Number 9, September 2007

EnviroNews Science Selections

Aspartame Cancer Risks Revisited
Prenatal Exposure May Be Greatest Concern

M. Nathaniel Mead

19,000 people, the 4% of users of aspartame who drink average 5 cans daily, have more problems in NIH AARP study of 474,000 people: Murray 2007.09.21 http://RMForAll.blogspot.com September 21, 2007
http://groups.yahoo.com/group/aspartameNM/message/1475

This is the first good data about the percentage of aspartame users who use over 3 cans daily, averaging 5 cans daily at 200 mg per 12 oz can diet soda.

About 4% of 473,984 is 19,000 people, with a peak intake of 17 cans daily, and average 5 cans daily.

It would be worthwhile to investigate a wide variety of symptoms for the 0.1% of highest level users, about 2,000 people.

For about 200 million USA aspartame users, this would be 200,000 people.

Table 1 reveals consistent increase in problems from zero to (400 - 600) to (over 600) mg/d aspartame intake:

% of cohert ---------- 46 -------- 5 -------- 4 %

Mean aspartame mg/d --- 0 -------441 ------ 986

16+ education -------- 37 ------- 40 ------- 34 %

Diabetes history ------ 3 ------- 22 ------- 26 %

Alcohol g/d ---------- 14 ------- 11 ------- 13

Never smoke ---------- 36 ------- 31 ------- 29 %

Body Mass Index ------ 26 ------- 29 ------- 29

18.5 - 25 ------------ 42 ------- 21 ------- 19 %

30 - 35 -------------- 13 ------- 23 ------- 26 %

Over 35 -------------- 4 ------- 10 ------- 13 %

Physical activity %:

Under 3-4/mo --------- 32 ------- 32 ------- 37 %

Under 1-2/wk --------- 22 ------- 21 ------- 19 %

Over 3-4/wk ---------- 45 ------- 45 ------- 43 %

Calories kcal ----- 1,919 ---- 1,855 ---- 2,044 %

Caffeine mg/d ------ 393 ------ 364 ------ 424

There do seem to be many increases of problems from the second to third row, as mean aspartame use doubles.

Granted, this is cherry picking the data, selecting interesting patterns.

Correlations alone do not prove any direction of causation.

Nevertheless, it may be of value to study the correlations for increasing aspartame intake among the 4 % using over 600 mg, the equivalent of 3 cans 12-oz cans diet soda daily. The average use for this group is 5 cans daily.

For instance, are a minority of these heavy users displaying the great majority of the problems that are reflectted in the mean for each level of use, with most users only having little or no increase in problems?

This is a group of about 20,000 people.

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Nurses Health Study can quickly reveal the extent of aspartame (methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21

The Nurses Health Study is a bonanza of information about the health of probably hundreds of nurses who use 6 or more cans daily of diet soft drinks -- they have also stored blood and tissue samples from their immense pool of subjects, over 100,000 for decades.

Aspartame and Psychiatric Disorders, Ralph G. Walton, MD: Murray "Of course, everyone chooses, as a natural priority, to actively find, quickly share, and positively act upon the facts about healthy and safe food, drink, and environment."
http://RMForAll.blogspot.com new primary archive
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Aspartame and Psychiatric Disorders, Ralph G. Walton, M.D.: Murray 2007.09.20
http://rmforall.blogspot.com Wednesday, September 19, 2007
[You are invited to give civil, relevant comments.]
http://groups.yahoo.com/group/aspartameNM/message/1474

Food additives and hyperactive behaviour in kids, McCann D, Grimshaw K, Sonuga-Barke, Warner JO, Stevenson J, et al, The Lancet 2007.09.06 pdf 454 KB: Murray 2007.09.06
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"Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population."

Highly toxic formaldehyde, the cause of alcohol hangovers, is made by the body from 100 mg doses of methanol from dark wines and liquors, dimethyl dicarbonate, and aspartame: Murray 2007.08.31
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http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L (becomes formaldehyde in body): EU Scientific Committee on Foods 2001.07.12: Murray 2004.01.22

http://europa.eu.int/comm/food/fs/sc/scf/out96_en.pdf

"...DMDC was evaluated by the SCF in 1990 and considered acceptable for the cold sterilization of soft drinks and fruit juices at levels of addition up to 250 mg/L (1) ...DMDC decomposes primarily to CO2 and methanol ...

[Note: Sterilization of bacteria and fungi is a toxic process, probably due to the inevitable conveersion in the body of methano into highly toxic formaldehyde and then formic acid.]

The use of 200 mg DMDC/L would add 98 mg/L of methanol to wine which already contains an average of about 140 mg/L from natural sources.

A healthy person metabolises 1500 mg methanol/hr without any physiological problems and this should be compared to the amount of up to 240 mg/L methanol in wine, treated with DMDC up to 200 mg/L.

Formaldehyde induced urticarial vasculitis in male medical student, age 40, Michael Pellizzari, Gillian Marshman, Flinders U., Australasian J. Dermatol. 2007 Aug: Murray 2007.08.29
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"A complete recovery occurred only after strict elimination of all exposure to formaldehyde, both occupationally and in the home environment, was achieved."

4 cases of aspartame-induced thrombocytopenia [very low platelets in blood], HJ Roberts MD, Letter in Southern Medical Journal 2007 May: 100(5); 543: Murray 2007.08.25
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Direct and indirect cellular effects of aspartame on the brain, Humphries P, Pretorius E, Naude H, U. Pretoria, South Africa, Eur J Clin Nutr. 2007 Aug 8: Murray 2007.08.12
http://groups.yahoo.com/group/aspartameNM/message/1463

John O. Warner with U. Southampton team in 2007 finds kids hyperactive from six food colors, confirming their report in 2004 on study in 2000: Murray 2007.08.11
http://groups.yahoo.com/group/aspartameNM/message/1461

"Our study has shown that the effect of food additives on behaviour occurs independently of pre-existing hyperactive behaviour or indeed atopic status.

This is consistent with other studies which have tended to suggest that if food additives have an effect at all, it is via a pharmacological effect which is best exemplified by the non-IgE dependent histamine release. 20,21

We believe that this suggests that benefit would accrue for all children if artificial food colours and benzoate preservatives were removed from their diet.

These findings are sufficiently strong to warrant attempts at replication in other general population samples and to examine whether similar benefits of the removal of artificial colourings and sodium benzoate from the diet could be identified in community samples at older ages."

Third study by expert Greek team of neurotoxicity in infant rats by aspartame (or its parts, methanol, phenylalanine, aspartic acid), KH Schulpis et al, Food Chem Toxicol 2007.06.16: Murray 2007.08.05
http://groups.yahoo.com/group/aspartameNM/message/1459

Food Chem Toxicol. 2007 Jun 16;[Epub ahead of print]
The effect of aspartame metabolites on the suckling rat frontal cortex acetylcholinesterase. An in vitro study.

Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Experimental Physiology, Medical School
University of Athens
P.O. Box 65257, GR 15401 Athens, Greece

Aspartame (ASP) consumption is suggested to be implicated with muscarinic dysfunction.

The aim of this work was to evaluate the effect of ASP and its metabolites on acetylcholinesterase (AChE) activity in rat frontal cortex and pure enzyme.

Rat frontal cortex homogenate or pure enzyme AchE (eel E. Electricus) were incubated with ASP and each of ASP components, phenylalanine (Phe), aspartic acid (asp), and methanol (MeOH) for 1h at 37 degrees C.

AChE was measured spectrophotometrically.

The results showed that incubation of rat tissue or pure enzyme with the sum of ASP metabolites, as reported to be found in the CSF after 150 or 200mg/kg ASP consumption, inhibited frontal cortex and pure AChE about -11% to -29% (p<0.001).

Asp, Phe or MeOH concentrations related to their CSF levels after ingestion of abuse or toxic ASP doses, when separately incubated with frontal cortex or pure AChE, resulted in a significant decrease of the enzyme activities.

In conclusion:

ASP compounds may directly and/or indirectly act on the frontal cortex AChE.

High or toxic doses of the sweetener remarkably decreased the enzyme activity.

If this in vitro finding comes into human reality, it may be suggested that cholinergic symptoms are related to the consumption of the above ASP doses. PMID: 17673349

http://groups.yahoo.com/group/aspartameNMmessage/1447
Second study by expert Greek team of neurotoxicity in infant rats by aspartame (or its parts, methanol, phenylalanine, aspartic acid), KH Schulpis et al, Toxicology 2007.05.18: Murray 2007.07.04

Toxicology. 2007 May 18; [Epub ahead of print]
l-Cysteine and glutathione restore the reduction of rat hippocampal Na(+), K(+)-ATPase activity induced by aspartame metabolites.
Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Experimental Physiology
Medical School, Athens University
P.O. Box 65257, GR-15401 Athens, Greece

Studies have implicated aspartame (ASP) ingestion in neurological problems.

The aim of this study was to evaluate hippocampal Na(+),K(+)-ATPase and Mg(2+)-ATPase activities after incubation with ASP or each of ASP metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (asp) separately.

Suckling rat hippocampal homogenates or pure Na(+),K(+)-ATPase were incubated with ASP metabolites.

Na(+),K(+)-ATPase and Mg(2+)-ATPase activities were measured spectrophotometrically.

Incubation of hippocampal or pure Na(+),K(+)-ATPase with ASP concentrations (expected in the cerebrospinal fluid (CSF)) after ASP consumption of 34, 150 or 200 mg/kg resulted in hippocampal enzyme activity reduction of 26%, 50% or 59%, respectively, whereas pure enzyme was remarkably stimulated.

Moreover, incubation with hippocampal homogenate of each one of the corresponding in the CSF ASP metabolites related to the intake of common, high/abuse doses of the sweetener, inhibited Na(+),K(+)-ATPase, while pure enzyme was activated.

Hippocampal Mg(2+)-ATPase remained unaltered.

Addition of l-cysteine (cys) or reduced glutathione (GSH) in ASP mixtures, related with high/toxic doses of the sweetener, completely or partially restored the inactivated membrane Na(+),K(+)-ATPase, whereas the activated pure enzyme activity returned to normal.

CSF concentrations of ASP metabolites related to common, abuse/toxic doses of the additive significantly reduced rat hippocampal Na(+),K(+)-ATPase activity, whereas pure enzyme was activated.

Cys or GSH completely or partially restored both enzyme activities. PMID: 17602817

Kleopatra H. Schulpis, MD, PhD. Institute of Child Health
Aghia Sophia Children's Hospital, GR-11527 Athens (Greece)
Tel. +30 1 7708291, Fax +30 1 7700111 inchildh@otenet.gr

//////////////////////////////////////////////////////////

http://groups.yahoo.com/group/aspartameNMmessage/1444
Expert Greek group finds aspartame (or its parts, methanol, phenylalanine, aspartic acid) harm infant rat brain enzyme activity, KH Schulpis et al, Pharmacol. Res. 2007.05.13: Murray 2007.06.23

Pharmacol Res. 2007 May 13; [Epub ahead of print]
The effect of aspartame on acetylcholinesterase activity in hippocampal homogenates of suckling rats.
Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Experimental Physiology
Medical School, University of Athens,
P.O. Box 65257, GR-15401 Athens, Greece

BACKGROUND:

Neurological disturbances have been implicated with aspartame (ASP)consumption, and the cholinergic system with acetylcholinesterase (AChE) seems actively involved.

AIM:

To evaluate the effect of ASP and its metabolites on rat hippocampal AChE activity.

METHODS:

Hippocampal homogenate or pure enzyme AChE (eel E. electricus) was incubated with the sum or each of ASP components, phenylalanine (Phe), aspartic acid (asp) and methanol (MeOH) for 1 h at 37 degrees C.

AChE activity was measured spectrophotometrically.

RESULTS:

Incubation of rat tissue or pure enzyme with the sum of ASP metabolites in concentrations in CSF (the concentrations were calculated according to the CSF/plasma concentration ratios) following 150 or 200 mgkg(-1) of ASP consumption, resulted in significant enzyme activity reductions of 25 and 31% for hippocampal AChE and 11% (p<0.01) and 19% for pure enzyme, respectively.

Aspartic acid concentrations of 0.42 or 0.56 mM significantly reduced the enzyme activities by 13 and 20% for hippocampal AChE and 15 and 18% for pure enzyme, respectively.

Phe concentrations of 0.042 or 0.083mM decreased the enzyme activity by 12% (p<0.01) and 20% (p><0.001) for hippocampal AchE and 15 and 18% (p<0.001) for pure enzyme, respectively.

Methanol concentrations of 0.60 or 0.80 mM remarkably inhibited hippocampal AChE by about 18 and 22% and pure enzyme by about 14 and 20%, respectively.

CONCLUSIONS:

Low concentrations of ASP components had no effect on hippocampal and pure AChE activity, whereas high or toxic concentrations remarkably decreased both enzyme activities.

Muscarinic symptoms may be related to the latter concentrations of ASP metabolites. PMID: 17580119

Kleopatra H. Schulpis, MD, PhD. Institute of Child Health
Aghia Sophia Children's Hospital, GR-11527 Athens (Greece)
Tel. +30 1 7708291, Fax +30 1 7700111 inchildh@otenet.gr

http://groups.yahoo.com/group/aspartameNM/message/1279

All three aspartame metabolites harm human erythrocyte [red blood cell] membrane enzyme activity, KH Schulpis et al, two studies in 2005, Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock: Murray 2006.01.14

"High or abuse concentrations of ASP hydrolysis products significantly decreased the membrane enzyme activity, which was completely or partially prevented by L-cysteine or reduced GSH."

[Definition of Erythrocyte
Erythrocyte:
A cell that contains hemoglobin and can carry oxygen to the body. Also called a red blood cell (RBC). The reddish color is due to the hemoglobin. Erythrocytes are biconcave in shape, which increases the cell's surface area and facilitates the diffusion of oxygen and carbon dioxide. This shape is maintained by a cytoskeleton composed of several proteins. Erythrocytes are very flexible and change shape when flowing through capillaries. Immature erythrocytes, called reticulocytes, normally account for 1-2 percent of red cells in the blood.]

Eur J Clin Nutr. 2005 Dec 14; [Epub ahead of print]
The effect of L-cysteine and glutathione on inhibition of Na(+), K(+)-ATPase activity by aspartame metabolites in human erythrocyte [red blood cell] membrane.
Schulpis KH, Kleopatra H. Schulpis, MD, PhD.
Institute of Child Health, Aghia Sophia Children's Hospital, GR-11527 Athens (Greece) +30 1 7708291, Fax +30 1 7700111
inchildh@otenet.gr
Papassotiriou I, biochem@paidon-agiasofia.gr
Tsakiris T, Tsakiris S. Stylianos Tsakiris. stsakir@cc.uoa.gr
1 Institute of Child Health, Research Center
'Aghia Sophia' Children's Hospital, Athens, Greece.
ggbriass@med.uoc.gr ersi_voskaridou@yahoo.com
mmoschov@med.uoa.gr siahanidou@hotmail.com

Background:

Reports have implicated Aspartame (N-L-a-aspartyl-L-phenylalanine methyl ester, ASP) in neurological problems.

Aim:

To evaluate Na(+), K(+)-ATPase activities in human erythrocyte [red blood cell] membranes after incubation with the ASP metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (Asp).

Methods:

Erythrocyte [red blood cell] membranes were obtained frrom 12 healthy individuals an were incubated at 37 degrees C for 1 h with the sum or each of the ASP metabolites separately, which are commonly measured in blood after ASP ingestion.

Na(+), K(+)-ATPase and Mg(2+)-ATPase activities were measured spectrophotometrically.

Results:

Membrane Mg(2+)-ATPase activity was not altered.

The sum of ASP metabolite concentrations corresponding to 34, 150 or 200 mg/kg of the sweetener ingestion resulted in an inhibition of the membrane Na(+), K(+)-ATPase by -30, -40, -48%, respectively.

MeOH concentrations of 0.14, 0.60 or 0.80 mM decreased the enzyme activity by -25, -38, -43%, respectively.

Asp concentrations of 2.80, 7.60 or 10.0 mM inhibited membrane Na(+), K(+)-ATPase by -26, -40, -46%, respectively.

Phe concentrations of 0.14, 0.35 or 0.50 mM reduced the enzyme activity by -24, -44, -48%, respectively.

Preincubation with L-cysteine or reduced glutathione (GSH) completely or partially restored the inhibited membrane Na(+), K(+)-ATPase activity by high or toxic ASP metabolite concentrations.

Conclusions:

Low concentrations of ASP metabolites had no effect on Na(+), K(+)-ATPase activity.

High or abuse concentrations of ASP hydrolysis products significantly decreased the membrane enzyme activity, which was completely or partially prevented by L-cysteine or reduced GSH. [reduced glutathione]

European Journal of Clinical Nutrition advance online publication, 14 December 2005; doi:10.1038/sj.ejcn.1602355. PMID: 16391576

http://groups.yahoo.com/group/aspartameNM/message/1213
Aspartame (methanol, phenylalanine, aspartic acid) effects, detailed expert studies in 2005 Aug and 1998 July, Tsakiris S, Schulpis KH, Karikas GA, Kokotos G, Reclos RJ, et al, Aghia Sophia Children's Hospital, Athens, Greece: Murray 2005.09.09

[The lowest dose level tested, 34 mg aspartame per kg body weight, well below the FDA daily human limit of 50 mg/kg, 16 12-oz cans, caused enzyme activity reduction by -33% in human red blood cell membranes.] However, a missed opportunity in both studies is that the inevitable, extremely and cumulatively toxic products of methanol in the human body, formaldehyde and formic acid, which are responsible for the toxicity of methanol, were not independently tested.

"It is concluded that low concentrations of ASP metabolites had no effect on the [human red blood cell] membrane enzyme activity, whereas high or toxic concentrations partially or remarkably decreased the [human red blood cell] membrane AChE activity, respectively. Additionally, neurological symptoms, including learning and memory processes, may be related to the high or toxic concentrations of the sweetener metabolites."]

Pharmacol Res. 2005 Aug 26; [Epub ahead of print]
The effect of aspartame metabolites on human [red blood cell] erythrocyte membrane acetylcholinesterase activity.
Tsakiris S, Giannoulia-Karantana A, Simintzi I, Schulpis KH.
Department of Experimental Physiology, Medical School
University of Athens, P.O. Box 65257, GR-154 01 Athens, Greece.

Stylianos Tsakiris. stsakir@cc.uoa.gr

Giannoulia-Karantana A. First Department of Pediatrics, Aghia Sophia Children's Hospital, University of Athens, Greece.

Kleopatra H. Schulpis, MD, PhD. Institute of Child Health, Aghia Sophia Children's Hospital, GR-11527 Athens (Greece) Tel. +30 1 7708291, Fax +30 1 7700111 inchildh@otenet.gr [Papoutsakis T. tina.papoutsakis@hua.gr

Papadopoulos G. Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26, 41221 Larisa, Greece papg@chem.auth.gr]

Abstract:

Studies have implicated aspartame (ASP) with neurological problems. The aim of this study was to evaluate acetylcholinesterase (AChE) activity in human erythrocyte [red blood cell] membranes after incubation with the sum of ASP metabolites, phenylalanine (Phe), methanol (met) and aspartic acid (aspt), or with each one separately.

Erythrocyte [human red blood cell] membranes were obtained from 12 healthy individuals and were incubated with ASP hydrolysis products for 1h at 37 degrees C. AChE was measured spectrophotometrically.

Incubation of membranes with ASP metabolites corresponding with 34 mg/kg, 150 mg/kg or 200 mg/kg of ASP consumption resulted in an enzyme activity reduction by -33%, -41%, and -57%, respectively.

Met concentrations 0.14 mM, 0.60 mM, and 0.80 mM decreased the enzyme activity by -20%, -32% or -40%, respectively.

Aspt concentrations 2.80 mM, 7.60 mM or 10.0 mM inhibited membrane AChE acitivity by -20%, -35%, and -47%, respectively.

Phe concentrations 0.14 mM, 0.35 mM or 0.50 mM reduced the enzyme activity by -11%, -33%, and -35%, respectively.

Aspt or Phe concentrations 0.82 mM or 0.07 mM, respectively, did not alter the membrane AChE activity.

It is concluded that low concentrations of ASP metabolites had no effect on the membrane enzyme activity, whereas high or toxic concentrations partially or remarkably decreased the membrane AChE activity, respectively. Additionally, neurological symptoms, including learning and memory processes, may be related to the high or toxic concentrations of the sweetener metabolites. PMID: 16129618

http://groups.yahoo.com/group/aspartameNM/message/939
Aspartame (aspartic acid, phenylalanine) binding to DNA: Karikas July 1998: Murray 2003.01.05 rmforall Karikas GA, Schulpis KH, Reclos GJ, Kokotos G Measurement of molecular interaction of aspartame and it's metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7. Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@atlas.uoa.gr
G.J. Reclos reklos@otenet.gr

FEMA slow to safety test Katrina toxic trailers, Charles Babington, Associated Press -- 1 ppm formaldehyde in air is about half the daily dose from 3 cans aspartame diet soda and ten times the 1999 EPA alarm level for drinking water: Murray 2007.07.23
http://groups.yahoo.com/group/aspartameNM/message/1455

Souring on fake sugar (aspartame), Jennifer Couzin, Science 2007.07.06: 4 page letter to FDA from 12 eminent USA toxicologists re two Ramazzini Foundation cancer studies 2007.06.25: Murray 2007.07.18
http://groups.yahoo.com/group/aspartameNM/message/1453

"In light of the new aspartame study, which extends and corroborates the finding from an earlier study, we urge the FDA to immediately commence a careful review of the new study.

Considering how widely aspartame in consumed by young children, as well as adults, in the United States and abroad, it is essential that this review be done as expeditiously as possible.

If that review confirms that aspartame caused cancer in the laboratory animals, the FDA must invoke the Delaney amendment and revoke its approval for the artificial sweetener.8"

www.ramazzini.it/fondazione/pdfUpload/Science_06.07.2007.pdf

Phenylalanine and aspartic acid from low dose aspartame in rabbits interfere with blood coagulation, Pretorius E and Humphries P, U. of Pretoria, Ultrastruct Pathol 2007 March: Murray 2007.07.14
http://groups.yahoo.com/group/aspartameNMmessage/1452

"The authors conclude by suggesting that aspartame usage may interfere with the coagulation process and might cause delayed fibrin breakup after clot formation.p> They suggest this, as the fibrin networks from aspartame-exposed rabbits are more complex and dense, due to the netlike appearance of the minor, thin fibers.

Aspartame usage should possibly be limited by people on anti-clotting medicine or those with prone to clot formation."

Ultrastruct Pathol. 2007 Mar-Apr; 31(2): 77-83.
Ultrastructural changes to rabbit fibrin and platelets due to aspartame.
Pretorius E, Humphries P.
Department of Anatomy, Faculty of Medicine
University of Pretoria, South Africa
[Humphries P also at Department of Anatomy, University of Limpopo. Medunsa Campus, Garankuwa. South Africa]

email: E. Pretorius resia.pretorius@up.ac.za

*Correspondence to E. Pretorius
BMW Building, PO Box 2034,
Faculty of Health Sciences
University of Pretoria, Pretoria 0001, South Africa