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Home > Archive > Psoriasis support > September 2005 > eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV Belsito, No
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eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV Belsito, No
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| Rich Murray 2005-09-24, 1:40 pm |
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http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 2003.30.04 2005.09.08
Rich Murray, MA Room For All rmforall@comcast.net 505-501-2298
1943 Otowi Road Santa Fe, New Mexico 87505 USA
http://groups.yahoo.com/group/aspartameNM/messages
group with 148 members, 1,212 posts in a public, searchable archive
[ Comments by Rich Murray are in square brackets. To increase the
readability of the dense, specialized, condensed text of a brief scientific
letter (usually not peer reviewed), I have added spacing without altering
text, while correcting minor typos.
I then offer some critical analyses and extensions of the references, since
the relevant scientific literature is contaminated by long-term, systematic
influence by corporate vested interests. ]
"A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis...
By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.
Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.
She had begun using an aspartame-based artificial sweetener 5 months prior
to the onset of her dermatitis. [ 12 months of low-level aspartame use until
stopping. ]
Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
completely and has not recurred over 18 months without specific
treatment....
Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied."
[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
soda gives 200 mg aspartame. An aspartame reactor can have immediate strong
symtoms from an under-the-tongue wafer with 4 mg aspartame.
(Appendix A, for comments, abstracts, and links.) ]
Contact Dermatitis. 2003 Nov; 49(5): 258-9.
Systemic contact dermatitis of the eyelids caused by formaldehyde derived
from aspartame?
Hill AM, Belsito DV. DBelsito@kumc.edu
Division of Dermatology, university of Kansas Medical Center, 3901 Rainbow
Blvd., Kansas City, KS 66160, USA. PMID: 14996049
A. Michele Hill and Donald V. Belsito
Division of Dermatology, university of Kansas Medical Center
3901 Rainbow Blvd., Kansas City, KS 66160, USA [ (Appendix B, for more
abstracts by Donald V. Belsito, selections, and institutions) ]
Key Words: allergic contact dermatitis; aspartame; eyelids; formaldehyde;
systemic contact dermatitis.
Formaldehyde is a common and ubiquitous contact allergen.
Sources of exposure include hair and skin care products, cosmetics, topical
medications, permanent press clothing, cleaning agents, disinfectants, paper
and even smoke. [ Also, new buildings, mobile homes, furniture, carpets,
drapes, particleboard, medical facilities, methanol, aspartame, dimethyl
dicarbonate, dark wines and liquors ]
Sensitization is reported in between 2.2 and 9.6% of patients patch tested
(1,2).
[ (Appendix C, for abstracts on rates of formaldehyde sensitivity in control
groups, as a possible first estimate of the impact of widespread exposure to
aspartame since 1981.) ]
Case Report
A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis.
A corticosteroid-containing opthalmologic ointment improved but did not
clear the rash.
She failed to improve when she discontinued the use of all eyelid cosmetics
and nail polishes for 2 months.
She had had a facial dermatitis in 1995, for which she had been patch tested
and found to be allergic to formaldehyde, quaternium-15 and fragrances.
She had also had incidental, non-relevant reactions to neomycin and
ethylenediamine.
Her dermatitis had resolved with a change to formaldehyde-, quaternium-15
and fragrance-free facial and nail cosmetics.
There was no personal or family history of atopy or psoriasis.
Her only oral medication was celecoxib that she had taken for years prior to
the onset of her blepharitis.
She had also taken multivitamins, calcium and flaxseed oil for many years.
She worked as a homemaker and library volunteer. [ It is relevant as to
whether she had the standard urban diet with high protein and animal fats,
meats, milk products, some inorganic fruits and vegetables, high sugars,
and processed foods. Mercury dental amalgams and mercury contaminated fish
could also play a role. Was her water fluoridated or otherwise
contaminated? Were there toxic mold exposures in her environment? Was she
exposed to pesticides in her area? ]
Her eyelid dermatitis was kept clear with tacrolimus 0.03% ointment X2
daily.
She underwent patch testing to the North American Contact Dermatitis Group
standard tray, the university of Kansas' supplemental standard tray, and to
her cosmetics, cleansers, skin and hair care products and topical
medications.
She had relevant positive reactions at days 2 and 4 to formaldehyde (++),
quaternium-15 (++), diazolidinyl urea (+), DMDM hydantoin (+) and
imidazolidinyl urea (++), her hair care products and cleansers containing
multiple sources of these allergens.
She was extensively instructed in avoidance of formaldehyde and formaldehyde
releasers, as well as that of her multiple, currently non-relevant
allergens, including fragrance, benzalkonium chloride, neomycin, bacitracin,
p-phenylenediamine and black rubber mix. [ As a medical layman, I'm
disturbed to see all these chemicals that I know nothing about. ]
By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.
Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.
She had begun using an aspartame-based artificial sweetener 5 months prior
to the onset of her dermatitis. [ 12 months of low-level aspartame use until
stopping. Aspartame reactors discover this possibiliy usually from the Net,
alternative medicine providers, media, nurses, friends, and pharmacists,
rarely from physicians. ]
Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
completely and has not recurred over 18 months without specific treatment.
[ This quick healing response is typical of cases of low-level use with few
symptoms. Long-term heavy users , above 2 L, about 6 12-oz cans daily for
years, often have severe craving and withdrawal symptoms for weeks, with
gradual recovery for months. H. J. Roberts, MD has summarized over 1200
cases. (Appendix H) Three recent case reports are added here.
(Appendix I) ]
Unfortunately, she refused to undergo rechallenge with the sweetener.
[ This is usually the case. Commonly, there is inadvertent reexposure,
with immediate painful symptoms, even with low doses. ]
Discussion
The artificical sweetener, aspartame, is consumed by 54% of adults in the
USA (3).
It has been reported to cause dry eyes and difficulty in wearing contact
lenses (3) but never allergic contact dermatitis. [ Reference (3) is given
in full here. (Appendix H) Roberts H J. Dry eyes from use of aspartame
(Nutrasweet): Associated insights concerning the Sjogren syndrome.
The Townsend Letter for Doctors, January 1994. Appendix H also quotes
several cases of eyelid dermatitis from his review of 1200 cases in
Aspartame Disease: An Ignored Epidemic (2001). ]
Aspartame, an L-aspartyl-L-phynylalanine methyl ester, is hydrolysed in the
intestine to phenylalanine (50%), aspartic acid (40%) and aspartaic acid
methyl ester (10%).
The methyl ester is then converted to methyl alcohol (methanol) and carried
by the portal vein to the liver.
Methanol is there oxidized to formaldehyde that is converted into formic
acid (formate) by alcohol dehydrogenase, aldehyde dehydrogenase and the
microsomal oxidase pathway.
This occurs not only in the liver, but also in other organs containing high
levels of these enzymes, including the eye (4,5).
Formaldehyde binds proteins and nucleic acids, forming adducts difficult to
eliminate via metabolism.
Trocho et al. (6) demonstrated the formation of formaldehyde adducts with
DNA and proteins after administration of 20 mg/kg 14C-labelled aspartame to
rats, concluding that these adducts were responsible for functional
alterations of proteins and for DNA mutations leading to autoimmunity, cell
death or malignant transformation. [ (Appendix E) gives links, comments,
and quotes for the debate on the key Trocho study. ]
In contrast to Trocho et al. (6), McMartin et al. (7) studied formaldehyde
levels after large doses (3,000 mg/kg) of 14C-labelled methanol and
14C-labelled formaldehyde in monkeys, which unlike rats are sensitive to the
toxicities of methanol.
No increased formaldehyde derived from methanol was found.
High levels of formic acid were found in all monkeys that were given
methanol or formaldehyde.
[ (Appendix F) reviews the major studies. Oppermann et al (1973, 1976)
found that 30% of the methanol from aspartame fed to monkeys remained in
body tissues, indubitably as toxic products of formaldehyde and formic acid.
They did not test methanol product retention in humans. McMartin et al
(1979) reported significant formaldehyde retention in the midbrain of one
monkey from oral aspartame, and substantial formic acid in liver, kidney,
optic nerve, cerebrum, and midbrain in two other monkeys. It is clear that
his formaldehyde assays were too insensitive to give valid measurements.
There has been a dearth of relevant primate and human studies ever since. ]
Based on the work of McMartin and al. (7), Tephly (8) concluded that the
radioactive carbon from methanol, which was found in DNA and protein by
Trocho et al., was due to the normal physiologic flow of single-carbon units
through the folate pathway.
Stegink et al. (9) have shown that doses of 100 mg/kg or greater of
aspartame are required to increase methanol blood levels (and thus,
presumable formaldehyde formic acid levels) above control.
This would be equivalent to consuming 35 cans of diet beverage at one
sitting for a 70 kg person. [ This is a typical aspartame industry PR ploy,
well designed to plant the impression that only absurdly huge amounts of
diet soda might supply damaging amounts of methanol-derived formaldehyde and
formic acid toxic residuals in body tissues, thus reducing methanol blood
levels. So, it is a classic red herring tactic to focus on methanol blood
levels.
http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall
It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans) is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time are partially eliminated as carbon dioxide and water.
However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459.]
If 10% of the methanol is retained as formaldehyde, that would give 12 mg
daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.
Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.
[ http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall ]
This long-term low-level chronic toxic exposure leads to typical patterns of
increasingly severe complex symptoms, starting with headache, fatigue, joint
pain, irritability, memory loss, and leading to vision and eye problems, and
even seizures. In many cases there is addiction. Probably there are immune
system disorders, with a hypersensitivity to these toxins and other
chemicals. (Appendixes D, E, F, G, H, I, J) ]
Leon et al. (10) studied doses of 75 mg/kg of aspartame daily for 24 weeks
and found no change in blood or urine methanol levels and no symptoms of
methanol toxicity.
The dose used in Leon's study is 25 times the 90th percentile daily
consumption of aspartame (11). [ Appendix E gives an abstract by Davoli
(1986), using a properly sensitive assay, that proved a temporary rise in
blood methanol levels in humans from a single aspartame dose. Trocho
pointed out that formaldehyde adducts are persistent and thus cumulative. It
is reasonable to state that with long-term chronic formaldehyde exposure, it
may take a long time to both accumulate adducts and develop markedly
increased sensitivity and a series of complex symptoms . Adequate studies
would have to test substantial exposures over a year or longer with large
numbers of vulnerable types of people and record all symptoms. ]
Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied.
[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
soda gives 200 mg aspartame. An aspartame reactor can have immediate strong
symtoms from an under-the-tongue wafer with 4 mg aspartame. (Appendix A,
for comments, abstracts, and links.) ]
However, it is possible that the eye, with its high level of metabolic
activity, could be affected by methanol (and subsequently formaldehyde)
released from these low levels of aspartame and respond as a localized
target organ to minute amounts of her known allergen, formaldehyde, or its
metabolite, formate.
It is also possible that the amplifying effects of cell-mediated immunity
might detect trace amounts of a chemical not identified by more standard
assays, such as blood or urine levels. [ (Appendix D gives Thrasher's data
about immune system reactions from long-term, low-level formaldehyde
exposure, while Martin Pall gives a complex general theory, specifically
discussing formaldehyde as a major trigger.)
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
Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame: Martin L. Pall: Murray:
12.9.2 rmforall
FASEB J 2002 Sep; 16(11): 1407-17.
NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and
organic solvents as the mechanism of chemical sensitivity in multiple
chemical sensitivity.
Pall ML. PMID: 12205032 [ 162 references, received 1.3.2 ]
School of Molecular Biosciences, Washington State University,
Pullman, Washington 99164-4660, USA. martin_pall@wsu.edu ]
Such a hypothesis might explain why her dermatitis was limited to the
eyelids and give clinical support to Trocho's theory of formaldehyde
adducts.
Unfortunately, without rechallenging her with aspartame, we cannot test this
hypothesis.
Nonetheless, her long-lasting remission following discontinuation of
aspartame intake suggests that its breakdown to formaldehyde may have been a
possible mechanism for her prior blepharitis.
References
1. Christophersen J, Menne' T, Tanghoj P, Andersen K E, Brandrup F.
Clinical patch test data evaluated by multivariate analysis.
Contact Dermatitis 1989: 21: 291-299.
2. Fransway AF, Schmitz N A.
The problem of preservation in the 1990s.
II. Formaldehyde and formaldehyde-releasing biocides: incidences of
cross-reactivity and the significance of the positive response to
formaldehyde.
Am J Contact Dermat. 1991: 2: 78-88.
3. Roberts H J. Dry eyes from use of aspatame (Nutrasweet):
Associated insights concerning the Sjogren syndrome.
The Townsend Letter for Doctors, January 1994. [ full text in Appendix H ]
4. Murray T G, Burton T C, Rajani C, Lewandowski M F,
Burke J M, Eells J T.
Methanol poisoning: A rodent model with structural and functional evidence
for reinal involvement.
Arch Opthalmol 1991: 109: 1012-1016.
5. Eells J T.
Methanol-induced visual toxicity in the rat.
J. Pharmacol Exp Ther 1991: 257: 56-63.
6. Trocho C., Pardo R, Fafecas I, Virgili J, Remesar X,
Fernandez-Lopez, J A.
Formaldehyde derived from dietary aspartame binds to tissue components in
vivo.
Life Sci 1998 1988: 63: 337-349. [ abstract and quotes in Appendix E )
7. McMartin K E, Mrtin-Amat G, Noker P E, Tephly T R.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Biochem Pharmacol 1979: 28: 645-649. [ abstract, quotes, discussion, related
studies in Appendix F ]
8. Tephly T R: Comments on the purported generation of formaldehyde from
the sweetener aspartame.
Life Sci 1999: 65: 157-160. [ letter, usually not peer-reviewed,
abstract in Appendix E ]
9. Stegink L D, Brummel M C, McMartin-Amat G., Filer L J, Baker G L,
Tephly T R.
Blood methanol concentrations in normal adult subjects administered abuse
doses of aspatame.
J Toxicol Environ Health 1981: 7: 281-290.
10. Leon A S, Hunninghake D B, Bell C, Rassin D K, Tephly T R.
Safety of long-term large doses of aspartame.
Arch Intern Med 1989: 149: 2318-2324.
11. Tschanz C., Butachko H, Stargel W, Kotsonis F N (eds).
The Clinical Evaluation of a Food Additive: Assessment of Aspartame
Boca Raton: CRC Press, 1996.
************************************************************
http://groups.yahoo.com/group/aspartameNM/message/1186
aspartame induces lymphomas and leukaemias in rats, full plain text,
M Soffritti, F Belpoggi, DD Esposti, L Lambertini: Ramazzini Foundation
study 2005.07.14: main results agree with their previous methanol and
formaldehyde studies: Murray 2005.09.08
http://www.ramazzini.it/fondazione/...tameGEO2005.pdf
" In rodents and humans,
APM is metabolised in the gastrointestinal tract
into three constituents:
aspartic acid, phenylalanine and methanol 3. "
" These experiments demonstrate that the increase in
lymphomas and leukaemias,
observed in the APM study,
could be related to methanol, a metabolite of APM,
which is metabolised to formaldehyde and then to formic acid,
both in humans and rats 3. "
" Yellowing of the coat was observed in animals exposed to APM, mainly at
the highest concentrations.
This change was previously observed in our laboratory in rats exposed
to formaldehyde administered with drinking water 9. "
1. The total number of rats was 1800. 1500 were given aspartame.
2. 44 [ 14.7 % ] of the 300 control rats, given no aspartame, developed
lymphomas and leukemias (hemolymphoreticular neoplasias ), and none had
malignant brain tumors.
Of 1500 rats given aspartame, 294 [ 19.6 % ] had lymphomas and leukemias
(hemolymphoreticular neoplasias), and 12 [ 0.8 % ] had malignant brain
tumors.
In their previous methanol study, reported Dec 2002, of 200 + 100 = 300
control rats, given no methanol, there were 41+ 15 = 56 [ 18.7% ]
lymphomas and leukemias (hemolymphoreticular neoplasias), while of 600 +
100 = 700 rats given methanol, there were 187 + 15 = 202 with the same
cancers [ 28.9 % ]. They added 100 rats given 15 ppm methanol to their
Table 3 summarizing the formaldehyde data in their formaldehyde study, in
which their 200 control rats had 15 of these cancers.
In their previous formaldehyde study, reported Dec 2002, 200 control rats,
given no formaldehyde, had 15 [ 7.5 %] lymphomas and leukemias
(hemolymphoreticular neoplasias), while of the 600 rats given formaldehyde,
121 [ 20.3 % ] had these cancers.
Probably, other factors, such as viruses, bacteria, molds, or toxic
chemicals in the air, water, and food, also facilitate these cancers.
http://www.ramazzini.it/eng/fondazi...agli.asp?id=210
http://groups.yahoo.com/group/aspartameNM/message/1185
Ramazzini Institute (Italy) lifetime study with 1800 rats shows aspartame at
human use levels causes cancer (methanol, formaldehyde, formic acid), M
Soffritti and F Belpoggi: Felicity Lawrence, The Guardian (UK): Murray
2005.07.15
http://groups.yahoo.com/group/aspartameNM/message/1189
Michael F Jacobson of CSPI now and in 1985 re aspartame toxicity, letter to
FDA Commissioner Lester Crawford; California OEHHA aspartame critique
2004.03.12; Center for Consumer Freedom denounces CSPI: Murray 2004.07.27
http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartam...02-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references
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/aspartam...e/methanol.html
"Scientific Abuse in Aspartame Research"
Gold points out that industry methanol assays were too insensitive to
properly measure blood methanol levels. ]
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). If 30% of
the methanol is turned into formaldehyde, the amount of formaldehyde is 18
times the USA EPA limit for daily formaldehyde in drinking water, 2 mg in 2
L water.
http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
Murray 2002.05.30 rmforall
Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%),
both ordinary amino acids, bound loosely together by methanol (wood alcohol,
11%). The readily released methanol from aspartame is within hours turned
by the liver into formaldehyde and then formic acid, both potent, cumulative
toxins.
http://groups.yahoo.com/group/aspartameNM/message/1182
Joining together: short review: research on aspartame (methanol,
formaldehyde, formic acid) toxicity: Murray 2005.07.08 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1071
research on aspartame (methanol, formaldehyde, formic acid) toxicity: Murray
2004.04.29 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full
plain text, 2001: substantial sources are degradation of fruit pectins,
liquors, aspartame, smoke: Murray 2005.04.02 rmforall
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