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rmforall
01-03-2007, 11:07 PM
Aspartame Controversy, in Wikipedia democratic encyclopedia, 72
references (including AspartameNM # 864 and 1173 by Murray), brief
fair summary of much more research: Murray 2007.01.01
http://groups.yahoo.com/group/aspartameNM/message/1395


"It is well known that formaldehyde (HCHO) and reactive oxygen species
(ROS), such as free radicals, are cytotoxic as well as potentially
carcinogenic.
Although the individual effects of these reactants on cells have been
investigated, the cytotoxicity exerted by the coexistence of HCHO and
reactive radicals is poorly understood."

Toxicology. 2005 Jun 1; 210(2-3): 235-45.
Cytotoxic effect of formaldehyde with free radicals via increment of
cellular reactive oxygen species.
Saito Y, Nishio K, Yoshida Y, Niki E. yoshida-ya@aist.go.jp,
yoshiro-saito@aist.go.jp,etsuo-niki@aist.go.jp,
[ included in Reference 50 of 72 in Aspartame Controversy, in
Widipedia democratic encyclopedia ]

[ Reference 21 is:
http://groups.yahoo.com/group/aspartameNM/message/864
Butchko, Tephly, McMartin: Alemany, aspartame formaldehyde adducts in
rats: Murray 2002.09.08 ]

http://en.wikipedia.org/wiki/Aspartame_controversy

[ Rich Murray: Without altering text, spacing has been added to
increase readability. ]

Aspartame controversy
>From Wikipedia, the free encyclopedia
Jump to: navigation, search
* This page was last modified 21:18, 23 December 2006.

Aspartame has been the subject of a vigorous public controversy
regarding its safety and the circumstances around its approval.
A few studies have recommended further investigation into alleged
connections between aspartame and diseases such as brain tumors, brain
lesions, and lymphoma.[1] [2] [3]
These findings, combined with notable conflicts of interest in the
approval process, have engendered vocal activism regarding the possible
risks of aspartame.[4] [5]

Contents

* 1 Known effects
o 1.1 Methanol and Formaldehyde
o 1.2 Phenylalanine
o 1.3 Aspartic acid
o 1.4 Aspartylphenylalanine diketopiperazine
o 1.5 Responses
o 1.6 Recently-published research
* 2 See also
* 3 External links
o 3.1 Films
o 3.2 Pro-aspartame
o 3.3 Anti-aspartame
o 3.4 News & General Articles
* 4 References

[edit] Known effects

In 1995, FDA Epidemiology Branch Chief, Thomas Wilcox reported that
aspartame complaints represented 75% of all reports of adverse
reactions to substances in the food supply from 1981 to 1995. [6]
Concerns about aspartame frequently revolve around symptoms and health
conditions that are allegedly caused by the sweetener.
A total of 92 different symptoms and health conditions were reported by
physicians and consumers,
although this does not mean physician-reported or self-reported health
effects are a basis for drawing scientific conclusions.[7]

Questions have been raised about brain cancer, lymphoma, and genotoxic
effects such as DNA-protein crosslinks,
but these questions are primarily not based on reported case histories.

The sources for reported symptoms and health conditions that have
raised questions include:

1. Reports and analysis of case histories in scientific journals and
at medical conferences

2. Symptoms reported to the FDA and other governmental agencies

3. Symptoms reported to non-governmental organizations, researchers,
and physicians

4. Reports of symptoms and health conditions in the media

5. Self-reported cases on the Internet.

There is debate in the scientific and medical community as to whether
these symptoms are or are not caused by short-term or long-term
exposure to aspartame.
Some human and animal studies have found adverse effects [8] [9] [10]
and some have found no adverse effects [11] [12] [13].

It is not only the results of the research that have been questioned,
but the design of the research that led to specific outcomes.
For example, in human research of aspartame, the aspartame is usually
provided in slow-dissolving capsules.
But the biochemical changes from ingesting aspartame in slow-dissolving
capsules are many times smaller than those from ingesting aspartame
dissolved in liquids (such as carbonated beverages).[14]

Some human studies provide more than the daily allowance of aspartame,
but in an encapsulated form.
Based on the above-cited research, the equivalent amount of
"real-world" aspartame in these human studies would be less.
Other questions that have been raised about aspartame research
involving the length of the studies,
the number of test subjects,
conflict of interest issues,
and improper testing procedures.

The debate over possible adverse health effects has focused mainly on
four chemical components of aspartame:

[edit] Methanol and Formaldehyde

There has been some concern that aspartame metabolism releases
methanol.[citation needed]
Methanol is quickly absorbed and distributed throughout the body.
It is quickly broken down into formaldehyde, formic acid, and then
shuttled into the energy production pathway.[citation needed]
The blindness caused by methanol's toxicity is due to the peculiarities
of methanol metabolism around the nerves in the eye rather than an
inherit toxicity of the molecule itself.[citation needed]
It is believed that the methanol cannot be a problem because:
(a) there is not enough methanol absorbed to cause toxicity,
(b) methanol and formaldehyde are already a by-product of human
metabolism, and
(c) there is more methanol in some alcoholic beverages and fruit juices
than is derived from aspartame ingestion.[15] [16]

Other scientists think
(a) fruit juices and alcoholic beverages always contain protective
chemicals such as ethanol that block conversion of methanol into
formaldehyde, but aspartame contains no protective factors,
(b) the levels of methanol and particularly formaldehyde have been
proven to cause chronic toxicity in humans, and
(c) the low levels of methanol and formaldehyde in human metabolism are
tightly-controlled such that significant increases from aspartame
ingestion are not safe.[17][18]

In 1998, a team of scientists in Spain conducted an experiment on
rodents to indirectly measure the levels of formaldehyde adducts in the
organs after ingestion of aspartame.
They did this by radiolabeling the methanol portion of aspartame.
The scientists concluded that formaldehyde bound to protein and DNA
accumulated in the brain, liver, kidneys and other tissues after
ingestion of either 20 mg/kg or 200 mg/kg of aspartame.[19]
However, it has been argued by Tephly that these scientists were not
directly measuring formaldehyde,
but simply measuring levels of some by-product of the methanol from
aspartame.[20]
Tephly thinks that the by-product was not formaldehyde.
The researchers have stated that the data in the experiment have proven
it was formaldehyde.[21]

[edit] Phenylalanine

One of the functional groups in aspartame is phenylalanine,
which is unsafe for those born with phenylketonuria.
Phenylalanine is an amino acid commonly found in foods.
Approximately 50% of aspartame (by mass) is broken down into
phenylalanine.
Because aspartame is metabolized and absorbed very quickly
(unlike phenylalanine-containing proteins in foods),
it is known that aspartame could spike blood plasma levels of
phenylalanine.[14][22]
The debate centers on whether a significant spike in blood plasma
phenylalanine occurs at typical aspartame ingestion levels,
whether a sudden influx of phenylalanine into the bloodstream adversely
affects uptake of other amino acids into the brain and the production
of neurotransmitters (since phenylalanine competes with other Large
Neutral Amino Acids (LNAAs) for entry into the brain at the blood brain
barrier), and
whether a significant rise in phenylalanine levels would be
concentrated in the brain of fetuses and be potentially neurotoxic.
Note that many of the nutritional supplements suppliers who are
denouncing aspartame as toxic also sell phenylalanine as a nutritional
supplement.

Based on case histories from aspartame users,
measuring levels of neurotransmitters in the brains of animals and
measuring the potential of aspartame to cause seizures in animals,
some scientists think that aspartame may affect neurotransmitter
production.[23][24][25]
They think that even a moderate spike in blood plasma phenylalanine
levels from typical ingestion may have adverse consequences in
long-term use.
They are especially concerned that the phenylalanine can be
concentrated in fetal brains to a potentially neurotoxic level.[26][27]
Other scientists think that a rise in blood plasma phenylalanine is
negligible in typical use of aspartame[28] and
their studies show no significant effects on neurotransmitter levels in
the brain or changes in seizure thresholds.[29][30][31]
In addition, they say that proven adverse effects of phenylalanine on
fetuses has only been seen when blood phenylalanine levels stay at high
levels as opposed to occasionally being spiked to high levels.[32]

[edit] Aspartic acid

Aspartic acid is an amino acid commonly found in foods.
Approximately 40% of aspartame (by mass) is broken down into aspartic
acid.
Because aspartame is metabolized and absorbed very quickly (unlike
aspartic acid-containing proteins in foods),
it is known that aspartame could spike blood plasma levels of
aspartate.[14][33]
Aspartic acid is in a class of chemicals known as excitatory amino
acids, which also includes glutamate (found in MSG).
At high levels, excitatory amino acids can be toxic and might be
considered excitotoxins.
Abnormally high levels of excitotoxins have been shown in hundreds of
animals studies to cause damage to areas of the brain unprotected by
the blood-brain barrier and a variety of chronic diseases arising out
of this neurotoxicity.[34][35]
The debate amongst scientists has been raging since the early 1970s,
when Dr. John Olney found that high levels of aspartic acid caused
damage to the brains of infant mice.[36]
Dr. Olney and consumer attorney, James Turner filed a protest with the
FDA to block the approval of aspartame.
The debate is complex and has focused on several areas:
(a) whether the increase in plasma aspartate levels from typical
ingestion levels of aspartame is enough to cause neurotoxicity in one
dose or over time,
(b) whether humans are susceptible to the neurotoxicity from aspartic
acid seen in some animal experiments,
(c) whether aspartic acid increases the toxicity of formaldehyde,
(d) whether neurotoxicity from excitotoxins should consider the
combined effect of aspartic acid and other excitotoxins such as
glutamic acid from monosodium glutamate.
The neuroscientists at a 1990 meeting of the Society for Neuroscience
had a split of opinion on the issues related to neurotoxic effects from
excitotoxic amino acids found in some additives such as aspartame.[37]

Some scientists think that humans and other primates are not as
susceptible to excitotoxins as rodents and therefore there is little
concern with aspartic acid from aspartame.[38][39]
While they agree that the combined effects of all food-based
excitotoxins should be considered[40],
their measurements of the blood plasma levels of aspartic acid after
ingestion of aspartame and monosodium glutamate demonstrate that there
is not a cause for concern.[41][42]
Other scientists think that primates are susceptible to excitotoxic
damage[43] and that humans concentrate excitotoxins in the blood more
than other animals.[44]
Based on these findings, they think that humans are approximately 5-6
times more susceptible to the effects of excitotoxins than are
rodents.[45]
While they agree that typical use of aspartame does not spike aspartic
acid to extremely high levels in adults,
they are particularly concerned with potential effects in infants and
young children,[46]
the potential long-term neurodegenerative effects of small-to-moderate
spikes on plasma excitotoxin levels[47], and
the potential dangers of combining formaldehyde exposure from aspartame
with excitotoxins given that chronic methanol exposure increases
excitoxin levels in susceptible areas of the brain [48][49] and
that excitotoxins may potentiate formaldehyde damage.[50]

[edit] Aspartylphenylalanine diketopiperazine

This type of diketopiperazine (DKP) is created in products as aspartame
breaks down over time.
For example, researchers found that 6 months after aspartame was put
into carbonated beverages, 25% of the aspartame had been converted to
DKP. [51]
Concern amongst some scientists has been expressed that this form of
DKP would undergo a nitrosation process in the stomach producing a type
of chemical that could cause brain tumors.[52][53]
Other scientists think that the nitrosation of aspartame or the DKP in
the stomach would not produce a chemical that would cause brain tumors.
In addition, only a minuscule amount of the nitrosated chemical would
be produced. [54]
There are very few human studies on the effects of this form of DKP.
However, a (one-day) exposure study showed that the DKP was tolerated
without adverse effects.[55]

[edit] Responses

There have been more than 600 studies on aspartame and thousands of
studies on aspartame breakdown products and metabolites. [citation
needed]

* The American Cancer Society argues that "since aspartame is
broken down into these components before it is absorbed into the blood
stream, aspartame in its initial form does not have the opportunity to
travel to target organs, including the brain, to cause cancer."[56]

* The Feingold Association has stated that aspartame "is reported
to cause a variety of neurological effects from headache to seizures
and brain tumors."[57]

* The American Heart Association concludes that "extensive
investigation so far hasn't shown any serious side effects from
aspartame."[58]

* The Association for Consumers Action on Safety and Health issued
a consumer alert related to the dangers of ingesting aspartame.[59]

* The National Cancer Institute argues "there is no evidence that
the regulated artificial sweeteners on the market in the United States
are related to cancer risk in humans."[60]

* The National Health Federation calls aspartame a "neurotoxic
artificial sweetener."[61]

* The Food and Drug Administration says that more than "100
toxicological and clinical studies it has reviewed confirm that
aspartame is safe for the general population."[62]

* The UK Campaign for Truth in Medicine (consumer organization)
says that "Aspartame is, by far, the most dangerous substance on the
market that is added to foods."[63]

[edit] Recently-published research

Since the FDA approved aspartame for consumption in 1981,
some researchers have suggested that a rise in brain tumor rates in the
United States may be at least partially related to the increasing
availability and consumption of aspartame.[52]
The results of a large seven-year study into the long-term effects of
eating aspartame in rats by the European Ramazzini Foundation for
cancer research in Bologna, Italy were released in July 2005.
The study of 1,900 rats found evidence that aspartame caused leukemia
and lymphoma cancer in female rats.
The study showed that there was no statistically significant link
between aspartame and brain tumors.

The study,[64] published in the European Journal of Oncology,
raised concerns about the levels of aspartame exposure.
However, the European Food Safety Authority's (EFSA) review found that
the European Ramazzini Foundation's conclusion that aspartame is a
carcinogen was flawed and not supported by the data.[65]
The American Food & Drug Administration's (FDA) review of the Razzamini
study is still pending.[66]

A more recent analysis of the European Ramazzini Foundation data
published in Environmental Health Perspectives found a link between
life-long aspartame consumption in the rats and cancer of the kidney
and peripheral nerves.[67]

A review of the Ramazzini study by the European Food Safety Authority
(EFSA), published 04 May 2006,
concluded that the increased incidence of lymphomas/leukaemias reported
in treated rats was unrelated to aspartame,
the kidney tumors found at high doses of aspartame were not relevant to
humans, and
that based on all available scientific evidence to date,
there is no reason to revise the previously established Acceptable
Daily Intake levels for aspartame.[68]
The European Ramazzini Foundation responded to the EFSA findings by
stating that they thought the 16% increase in incidence of lymphoma and
leukemia between the aspartame group and control group signified that
these cancers were caused by aspartame ingestion.[69]
As the EFSA had already addressed this in their 04 May 2006 press
release, no further press release was made.[70]

A study published in April 2006 sponsored by the National Cancer
Institute involved 340,045 men and 226,945 women, ages 50 to 69,
found no statistically significant link between aspartame consumption
and leukemias, lymphomas or brain tumors.[71]
The study used surveys filled out in 1995 and 1996 detailing food and
beverage consumption.
The researchers calculated how much aspartame they consumed, especially
from sodas or from adding the sweetener to coffee or tea.
The researchers report, "Our findings from this epidemiologic study
suggest that consumption of aspartame-containing beverages does not
raise the risk of hematopoietic or brain malignancies."

Critics of this study point out that while the study looked at humans,
it did not look at life-long aspartame consumption as did the Ramazzini
study.
The Ramazzini study simulated life-long consumption from childhood
through old age (e.g., simulating 60 to 90 years of use).
The new National Cancer Institute study looked at subjects who consumed
diet drinks during a 12-month period from 1995 to 1996.
The Ramazzini study had the disadvantage of being an animal study but
looked at life-long consumption of aspartame.
The National Cancer Institute study was a human study,
but only looked at subjects with relatively short-term consumption of
diet drinks.
Finally, the questionnaire did not ask users to estimate aspartame
consumption, only diet drink consumption.[72]

[edit] See also

* Sugar substitute

[edit] External links

[edit] Films

* Sweet Misery: A Poisoned World,
Google video *[1]. Directed by Cori Brackett and J. T. Waldron,
2004.
* David Icke on Aspartame
* Sweet Misery Trailer

[edit] Pro-aspartame

* Aspartame Information Service
* Aspartame Archives
* Aspartame -- American Council on Science and Health
* Sugar Substitutes (U.S. FDA web page)
* U.S. FDA web page "FDA Consumer" magazine article, "Artificial
Sweeteners: No Calories...Sweet!"
* Update on Aspartame Safety; EC Scientific Committee on Food (263
KB PDF)
* Health Canada
* GreenFacts.org: Review of the EC Scientific Committee's 2002
Update
* American Heart Association
* National Cancer Institute
* Multiple Sclerosis Foundation
* Site of the Calorie Control Council, which is, according to its
website, a "non-profit association representing the low-calorie and
reduced-fat food and beverage industry."

[edit] Anti-aspartame

* Aspartame Support Group
* Aspartame Toxicity Information Center
* Aspartame -- Dorway to Discovery
* How Excitotoxins Were Discovered
* Excitotoxins -- MSG and Aspartame
* Aspartame -- Mission Possible News/Articles
* Aspartame Consumer Safety Network
* Aspartame -- The Secret Danger
* Aspartame -- Former U.S. FDA Investigator
* Sweet Poison
* Update on Aspartame Safety; Response to EC Scientific Committee
on Food
* Responses to Aspartame and Its Effects on Health
* Nutrapoison, Part One by Alex Constantine
* Dangers of Aspartame Links Page

[edit] News & General Articles

* Deconstructing Dinner on Aspartame, featuring the European
Ramazzini Foundation study, Kootenay Co-op Radio CJLY, Canada, October
12, 2006
* Safety of Artificial Sweetener Called Into Question by MP, The
Guardian, UK, December 15, 2005
* The Straight Dope on aspartame
* Free E-course on Aspartame Dangers
* The Lowdown on Sweet? -- article in New York Times
* The Safety of Aspartame, The New York Times, USA, February 21,
2006
* Artificial Sweetener Given the All Clear, New Scientist, May 13,
2006
* Center for Disease Control Full Report on Aspartame Complaints
* "Kiss My Aspartame" -- the Urban Legends Reference Pages

[edit] References

1. ^ Olney, J.W., N.B. Farber, E. Spitznagel, L.N. Robins, 1996.
"Increasing Brain Tumor Rates: Is There a Link to Aspartame?" Journal
of Neuropathology and Experimental Neurology, Volume 55, pages
1115-1123.

2. ^ Soffritti, Morando, et al., "First Experimental Demonstration
of the Multipotential Carcinogenic Effects of Aspartame Administered in
the Feed to Sprague-Dawley Rats," Environmental Health Perspectives,
Volume 114(3):379-385, 2006.
http://www.ehponline.org/members/2005/8711/8711.pdf

3. ^ Roberts, H.J., "Does Aspartame Cause Human Brain Cancer,"
Journal of Advancement in Medicine, Volume 4(4):231-241, 1991.

4. ^ GAO 1986. "Six Former HHS Employees' Involvement in Aspartame's
Approval," United States General Accounting Office, GAO/HRD-86-109BR,
July 1986. http://archive.gao.gov/d4t4/130780.pdf

5. ^ Gordon, Gregory, United Press International Investigation,
"NutraSweet: Questions Swirl," 1987. http://www.dorway.com/upipaper.txt

6. ^ Food Chemical News, June 12, 1995, Page 27.

7. ^ Department of Health & Human Services (DHHS). (1993, April 1)
Adverse Reactions Associated with Aspartame Consumption (HFS-728).
Chief, Epidemiology Branch. Retrieved Oct 24, 2005 from
http://www.presidiotex.com/aspartame/Facts/92_Symptoms/92_symptoms.gif
(This is an image of part of the document)

8. ^ Walton RG, Hudak R, Green-Waite RJ, "Adverse reactions to
aspartame: double-blind challenge in patients from a vulnerable
population," Biological Psychiatry, Vol. 34, Pages 13-17, 1993

9. ^ Koehler SM, Glaros A, "The effect of aspartame on migraine
headache," Headache, Volume 28, pages 10-14, 1988

10. ^ Smith JD, Terpening CM, Schmidt SO, Gums JG, "Relief of
fibromyalgia symptoms following discontinuation of dietary
excitotoxins," The Annals of Pharmacotherapy, Volume 35, pages 702-706,
2001

11. ^ Spiers PA, Sabounjian L, Reiner A, Myers DK, Wurtman J, Schomer
DL, "Aspartame: neuropsychologic and neurophysiologic evaluation of
acute and chronic effects," American Journal of Clinical Nutrition,
Volume 68, pages 531-537, 1998

12. ^ Schiffman SS, Buckley CE 3rd, Sampson HA, Massey EW, Baraniuk
JN, Follett JV, Warwick ZS, "Aspartame and susceptibility to headache,"
New England Journal of Medicine, Volume 317, pages 1181-1185, 1987

13. ^ Gurney JG, Pogoda JM, Holly EA, Hecht SS, Preston-Martin S,
"Aspartame consumption in relation to childhood brain tumor risk:
results from a case-control study," Journal of The National Cancer
Institute, Volume 89, pages 1072-1074, 1997

14. ^ a b c NCBI, PubMed 3574137

15. ^ NCBI, pubmed 12180494

16. ^ sciencedirect article

17. ^ dorway.com about methanol

18. ^ holisticmed.com about methanol

19. ^ ncbi, PubMed 9714421

20. ^ NCBI, PubMed 12180494

21. ^ healthgroups yahoo, message 864 [ aspartameNM ]

22. ^ ncbi, PubMed 1946186

23. ^ ncbi PubMed 3319565

24. ^ ncbi, PubMed 3352866

25. ^ ncbi, PubMed 2442082

26. ^ dorway.com, elsas

27. ^ trustedhands.com, aspartame and pregnancy

28. ^ ncbi PubMed 2215254

29. ^ ncbi PubMed 2013754

30. ^ ncbi PubMed 2379890

31. ^ ncbi PubMed 2470165

32. ^ ncbi PubMed 3351801

33. ^ ncbi PubMed 3670074

34. ^ ISBN 0-89859-735-8

35. ^ holistic med.com, msg-review

36. ^ ncbi PubMed 5464249

37. ^ ncbi PubMed 2294587

38. ^ ncbi PubMed 810365

39. ^ ncbi PubMed 827619

40. ^ nlm.nih.gov document

41. ^ ncbi PubMed 903828

42. ^ ncbi PubMed 2909831

43. ^ ncbi PubMed 4626680

44. ^ holistic med.com stegink.jpg

45. ^ ncbi PubMed 6152304

46. ^ ncbi PubMed 1982368

47. ^ ncbi PubMed 7854587

48. ^ ncbi PubMed 12490131

49. ^ ncbi pubmed 12112376

50. ^ healthgroups @ yahoo: aspartameNM, message 1173

51. ^ ACS article jf000640a43

52. ^ a b ncbi PubMed 8939194

53. ^ ncbi PubMed 8505016

54. ^ ncbi PubMed 8990134

55. ^ ncbi PubMed 8409113

56. ^ cancer.org, aspartame

57. ^ feingold.org, 06-2003

58. ^ americanheart.org, doc 4447

59. ^ image on wikipedia

60. ^ cis.nci.nih.gov, 3-19

61. ^ The NHF, article 46

62. ^ FDA, sugar

63. ^ campaign for thruth, sugar body

64. ^ ramazzini.it, aspartameGE2005.pdf

65. ^ EFSA EU, press release 1472 EN

66. ^ FDA, 2006 news topic 1369

67. ^ ehp online, 2005, 8711.pdf

68. ^ EFSA EU, afc_opinions, 1471 en

69. ^ raazzini.it, doc 292

70. ^ EFSA EU, press release 1472 EN

71. ^ Seattle PI, NWSource, 265559_soda

72. ^ WNHO, diet questionnaire

Retrieved from "http://en.wikipedia.org/wiki/Aspartame_controversy"

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50. ^ healthgroups @ yahoo: aspartameNM, message 1173

http://groups.yahoo.com/group/aspartameNM/message/1173
five recent abstracts on formaldehyde damage to cells -- vitamin E and
selenium protect, Yoshiro Saito and Yasukazu Yoshida et al, O'Brien PJ
et al, Costa M et al: Murray 2005.06.07

[ Herein I give selections from aspartameNM post #1173. ]

[Rich Murray: Here is the abstract and four more that show that many
groups are intensively studying cell damage and death from
formaldehyde, and the role of chemicals that increase or decrease this
damage from
formaldehyde. ]

"It is well known that formaldehyde (HCHO) and reactive oxygen species
(ROS), such as free radicals, are cytotoxic as well as potentially
carcinogenic.
Although the individual effects of these reactants on cells have been
investigated, the cytotoxicity exerted by the coexistence of HCHO and
reactive radicals is poorly understood."

Toxicology. 2005 Jun 1; 210(2-3): 235-45.
Cytotoxic effect of formaldehyde with free radicals via increment of
cellular reactive oxygen species.
Saito Y, Nishio K, Yoshida Y, Niki E. yoshida-ya@aist.go.jp,
yoshiro-saito@aist.go.jp,etsuo-niki@aist.go.jp,

It is well known that formaldehyde (HCHO) and reactive oxygen species
(ROS), such as free radicals, are cytotoxic as well as potentially
carcinogenic.
Although the individual effects of these reactants on cells have been
investigated, the cytotoxicity exerted by the coexistence of HCHO and
reactive radicals is poorly understood.
The present study using Jurkat cells demonstrated that the coexistence
of HCHO with water-soluble radical initiator,
2,2'-azobis-[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH)
dramatically decreased cell viability,
and that under such conditions scant cell death was observable induced
by either of the reactants alone.
Based on the results of phosphatidylserine exposure and caspase
activation, this observed cell death, in fact,
was apparently necrotic rather than apoptotic.
To understand the mechanisms of the cell toxicity of HCHO and AIPH, we
assessed two kinds of oxidative stress markers
such as cellular glutathione (GSH) content and cellular ROS,
and the DNA-protein cross-links,
which formed as the result of HCHO treatment.
A marked decrease in total cellular GSH was observed not only in the
case of the coexistence conditions but also with AIPH alone.
Dichlorodihydrofluorescein (DCF) assay revealed that cellular ROS were
synergistically increased before cell death.
The formation of DNA-protein cross-links was observed in the presence
of HCHO and AIPH,
and the extent was similar to HCHO alone.
Co-incubation with semicarbazide, which inactivates HCHO,
prevented this cell death induced by a combination of HCHO and AIPH.
Semicarbazide also exhibited an inhibitory effect on the synergistic
increment of cellular ROS and the formation of DNA-protein cross-links.
These results suggest that the free radicals from AIPH induced GSH
reduction, while HCHO resulted in the formation of DNA-protein
cross-links,
eventuating in a synergistic, incremental increase of cellular ROS and
cell death brought about by this combination.
************************************************** **************


"The toxicity and carcinogenicity of formaldehyde (HCHO) has been
attributed to its ability to form adducts with DNA and proteins."

"This work demonstrates that DNA-protein cross-links can be formed in
vitro following exposure to a variety of industrial compounds and that
most cross-links are formed at cytotoxic concentrations."

"At higher HCHO concentrations, lipid peroxidation ensued followed by
cell death."

"Antioxidants and iron chelators protected against HCHO cytotoxicity."

Chem Biol Interact. 2001 Jan 30; 130-132(1-3): 285-96.
The formaldehyde metabolic detoxification enzyme systems and molecular
cytotoxic mechanism in isolated rat hepatocytes.
Teng S, Beard K, Pourahmad J, Moridani M, Easson E, Poon R, O'Brien PJ.
Faculty of Pharmacy, University of Toronto, 19 Russell St., Ont., M5S
2S2, Toronto, Canada.
[ O'Brien Prof Peter J THE LESLIE DAN FACULTY OF PHARMACY
416-978-2716 fax 416-978-8511 peter.obrien@utoronto.ca, ]

The toxicity and carcinogenicity of formaldehyde (HCHO) has been
attributed to its ability to form adducts with DNA and proteins.
A marked decrease in mitochondrial membrane potential and inhibition of
mitochondrial respiration that was accompanied by reactive oxygen
species
formation occurred when isolated rat hepatocytes were incubated with
low concentrations of HCHO in a dose-dependent manner.
Hepatocyte GSH was also depleted by HCHO in a dose-dependent manner.
At higher HCHO concentrations, lipid peroxidation ensued followed by
cell death.
Cytotoxicity studies were conducted in which isolated hepatocytes
exposed to HCHO were treated with inhibitors of HCHO metabolising
enzymes.
There was a marked increase in HCHO cytotoxicity when either alcohol
dehydrogenase or aldehyde dehydrogenase was inhibited.
Inhibition of GSH-dependent HCHO dehydrogenase activity by prior
depletion of GSH markedly increased hepatocyte susceptibility to HCHO.
In each case, cytotoxicity was dose-dependent and corresponded with a
decrease in hepatocyte HCHO metabolism and increased lipid
peroxidation.
Antioxidants and iron chelators protected against HCHO cytotoxicity.
Cytotoxicity was also prevented, when cyclosporine or carnitine was
added to prevent the opening of the mitochondrial permeability
transition pore which further suggests that HCHO targets the
mitochondria.
Thus, HCHO-metabolising gene polymorphisms would be expected to have
toxicological consequences on an individual's susceptibility to HCHO
toxicity and carcinogenesis. PMID: 11306052
************************************************** **************


"Chemicals such as cis-platinum, formaldehyde, chromate, copper, and
certain arsenic compounds have been shown to produce DNA-protein
cross-links in human in vitro cell systems at high doses, such as those
in the cytotoxic range."

J Toxicol Environ Health. 1997 Apr 11; 50(5): 433-49.
DNA-protein cross-links produced by various chemicals in cultured human
lymphoma cells.
Costa M, Zhitkovich A, Harris M, Paustenbach D, Gargas M.
Institute of Environmental Medicine, New York University Medical
Center,
New York 10016, USA. costam@charlotte.med.nyu.edu

Chemicals such as cis-platinum, formaldehyde, chromate, copper, and
certain arsenic compounds have been shown to produce DNA-protein
cross-links in human in vitro cell systems at high doses, such as those
in the cytotoxic range.
Thus far there have only been a limited number of other chemicals
evaluated for their ability to produce cross-links.
The purpose of the work described here was to evaluate whether select
industrial chemicals can form DNA-protein cross-links in human cells in
vitro.
We evaluated acetaldehyde, acrolein, diepoxybutane, paraformaldehyde,
2-furaldehyde, propionaldehyde, chloroacetaldehyde, sodium arsenite,
and a deodorant tablet [Mega Blue; hazardous component listed as
tris(hydroxymethyl)nitromethane].
Short- and long-term cytotoxicity was evaluated and used to select
appropriate doses for in vitro testing. DNA-protein cross-linking was
evaluated at no fewer than three doses and two cell lysate washing
temperatures (45 and 65 degrees C) in Epstein-Barr virus (EBV) human
Burkitt's lymphoma cells.
The two washing temperatures were used to assess the heat stability of
the DNA-protein cross-link, 2-Furaldehyde, acetaldehyde, and
propionaldehyde produced statistically significant increases in
DNA-protein cross-links at
washing temperatures of 45 degrees C, but not 65 degrees C, and at or
above concentrations of 5, 17.5, and 75 mM, respectively.
Acrolein, diepoxybutane, paraformaldehyde, and Mega Blue produced
statistically significant increases in DNA-protein cross-links washed
at 45 and 65 degrees C at or above concentrations of 0.15 mM, 12.5 mM,
0.003%, and
0.1%, respectively.
Sodium arsenite and chloroacetaldehyde did not produce significantly
increased DNA-protein cross-links at either temperature nor at any dose
tested.
Excluding paraformaldehyde and 2-furaldehyde treatments, significant
increases in DNA-protein cross-links were observed only at doses that
resulted in complete cell death within 4 d following dosing.
This work demonstrates that DNA-protein cross-links can be formed in
vitro following exposure to a variety of industrial compounds and that
most cross-links are formed at cytotoxic concentrations. PMID: 9140463
************************************************** *****


http://groups.yahoo.com/group/aspartameNM/message/1379
short aspartame (methanol, formaldehyde) toxicity research summary:
Murray 2007.01.01

"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."

Rich Murray, MA Room For All rmforall@comcast.net
505-501-2298 1943 Otowi Road Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 76 members, 1,395 posts in a public, searchable archive
http://RMForAll.blogspot.com

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books: updated research review of 2004.07.16:
Murray 2006.05.11


Coca-Cola carcinogenicity in rats, Ramazzini Foundation, F Belpoggi, M
Soffritti, Annals NY Academy Sciences 2006 Sept, parts of 17 pages:
Murray 2006.12.02
http://groups.yahoo.com/group/aspartameNM/message/1385

Fiorella Belpoggi & Morando Soffritti of Ramazzini Foundation prove
lifetime carcinogenicity of Coca-Cola, aspartame, and arsenic, Annals
of the NY Academy of Sciences: Murray 2006.11.28
http://groups.yahoo.com/group/aspartameNM/message/1382

http://groups.yahoo.com/group/aspartameNM/message/1383 aspartame

http://groups.yahoo.com/group/aspartameNM/message/1384 arsenic


soft drinks and adolescent hyperactivity, mental distress, conduct
problems, Lars Lien, Nanna Lien, Sonja Heyerdahl, Mayne Thoresen, Espen
Bjertness 2006 Oct., A J Pub Health: Murray 2006.10.21
http://groups.yahoo.com/group/aspartameNM/message/1376

http://groups.yahoo.com/group/aspartameNM/message/1375
healthy diet, vitamins, and fish oil help reduce depression and
violence, studies by Joseph Hibbeln, Bernard Gesch, and Stephen
Schoenthaler, articles by Felicity Lawrence in UK Guardian Unlimited
and Pat Thomas in The Ecologist: Murray 2006.10.21


http://groups.yahoo.com/group/aspartameNM/message/1378
11 members of New Mexico legislature sign letter to ban aspartame as a
source of toxic methanol and formaldehyde, Stephen Fox, NM Senator
Gerald Ortiz y Pino: Murray 2006.10.22

http://groups.yahoo.com/group/aspartameNM/message/1374
47 UK Members of Parliament now support aspartame ban initiative of
Roger Williams, MP: Murray 2006.10.16


http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and brilliant blue,
harms nerve cells, eminent C. Vyvyan Howard et al, 2005
education.guardian.co.uk, Felicity Lawrence: Murray 2005.12.21

http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic -- aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13

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

http://groups.yahoo.com/group/aspartameNM/message/1366
toxicity in rat brains from aspartame, Vences-Mejia A, Espinosa-Aguirre
JJ et al 2006 Aug: Murray 2006.09.06

http://groups.yahoo.com/group/aspartameNM/message/1373
aspartame rat brain toxicity re cytochrome P450 enzymes, expecially
CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al, 2006 Aug,
Hum Exp Toxicol: relevant abstracts re formaldehyde from methanol
in alcohol drinks: Murray 2006.09.29


http://groups.yahoo.com/group/aspartameNM/message/1369
Bristol, Connecticut, schools join state program to limit artificial
sweeteners, sugar, fats for 8800 students, Johnny J Burnham, The
Bristol Press: Murray 2006.09.22

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools, Nancy Barnes,
New Milford Times: Murray 2006.05.25

http://groups.yahoo.com/group/aspartameNM/message/1353
carcinogenic effect of inhaled formaldehyde, Federal Institute of Risk
Assessment, Germany -- same safe level as for Canada:
Murray 2006.06.02

http://groups.yahoo.com/group/aspartameNM/message/1352
Home sickness -- indoor air often worse, as our homes seal in
pollutants
[one is formaldehyde, also from the 11% methanol part of aspartame],
Megan Gillis, WinnipegSun.com: Murray 2006.06.01


http://groups.yahoo.com/group/aspartameNM/message/1349
NIH NLM ToxNet HSDB Hazardous Substances Data Bank
inadequate re aspartame (methanol, formaldehyde, formic acid):
Murray 2006.08.19

http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~HwoSfJ:1
HSDB Hazardous Substances Data Bank: Aspartame

ASPARTAME CASRN: 22839-47-0
METHANOL CASRN: 67-56-1
FORMALDEHYDE CASRN: 50-00-0
FORMIC ACID CASRN: 64-18-6


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://www.HolisticMed.com/aspartame mgold@holisticmed.com
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2100

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall EU Scientific Committee on Food,
a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ):
59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/1371
Russell L. Blaylock, MD discusses MSG, aspartame, excitotoxins
with Mike Adams: Murray 2006.09.27

http://groups.yahoo.com/group/aspartameNM/message/1372
Mike Adams interviews Randall Fitzgerald on "The Hundred Year Lie:
How Food and Medicine are Destroying Your Health" 2006.06.21:
Murray 2006.09.28
************************************************** *****


http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 2002.01.17
Jerry D Smith, Chris M Terpening,
Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center,
Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic
disorder that is often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia
syndrome for two to 17 years are described.
All had undergone multiple treatment modalities with limited success.
All had complete, or nearly complete,
resolution of their symptoms within months after eliminating
monosodium glutamate (MSG) or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD Asst. Clinical Prof. siggy@shands.ufl.edu
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071
************************************************** *****