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msvnathan
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Topic Started by msvnathan
on 12/27/2008 2:41 AM
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Aspartame-Artificial Sweetener

Aspartame, an artificial sweetener used in 90 countries and found in 6,000 food & beverage products. It is mostly found in diet soft drinks and in chewing gum. It has bee recently found to cause everything from headaches to brain tumors. - Interview with Dr. Bernadene Magnuson

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rmforall
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Posted By rmforall on 12/28/2008 7:19 AM
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reasonable doubts re stevia approval: tobacco, alcohol drinks, and aspartame all expose people to methanol, formaldehyde, and formic acid: Rich Murray 2008.12.25

[ See also:

stevia herbal sweetener to be sold as Truvia (rebiana) by Cargill and Coca-Cola, if blitz of 12 studies wins FDA approval in 30-90 days: Murray 2008.05.24
http://rmforall.blogspot.com/2008_05_01_archive.htm
Saturday, May 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1540
____________________________________________________


As a volunteer medical layman information activist for aspartame toxicity and
related issues for nine years, during the last 5 years I have reviewed over two
dozen quality positive abstracts on stevia safety, and daily use about 1 tsp
green stevia powder myself, with no problems.

Reports of symptoms by users are extremely rare on the Net, while some reject
the taste.

Years ago, I encouraged the use of sucralose, only to find that its safety has
never been confirmed by adequate studies on humans, a substantial fraction of
its complex metabolites remains in the body, and there are increasing reports on
the Net of alarming symptoms.

Are these dozen studies science or yet another consummate industry propaganda
blitz, as has been the case for aspartame, neotame, sucralose, and Acesulfame-K?

If science, then financing has to be explicit, the authors, their resumes, and
full contact details listed, and, all texts put for free in the public domain.

All evidence and research re aspartame, stevia, and other sweetener toxicity
should be made fully and conveniently available for free.

The huge corporations and government agencies responsible for the major public
health debacle and cover up re aspartame rightfully should set up a hundred
billion dollar fund for compensation of injured citizens.

The evidence shows that stevia affects blood pressure and glucose. Therefore,
this is a drug. Few drugs indeed have no bad effects for some or many users.

All toxicity research has to be subject to fierce, reason and evidence based
public scrutiny and debate, open to all citizens, fully archived and searchable,
along with a perpetual record of all citizen and expert negative reports.

The authors of the dozen studies have strong conflicts of interest:

AG Renwick, AR Boobis, and GW Williams are defenders of aspartame, while many of
these authors work for Coca-Cola, Cargill, and Cantox, a dedicated industry
consultancy.

DJ Brusic ( an "independent toxicologist" ) and GW Williams are authors, both
members of Cantox and on the International Editorial Board of Food and Chemical
Toxicology.

AR Boobis is editor of Food Chemical Toxicology.

BA Magnuson and GW Williams of Cantox were authors of a massive, spurious review
in 2007, financed by Ajinomoto, that exonerated aspartame:

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

"Nearly every section of the Magnuson (2007) review has research
that is misrepresented
and/or crucial pieces of information are left out.

In addition to the misrepresentation of the research,
readers (including medical professionals) are often not told that
this review was funded by the aspartame manufacturer, Ajinomoto,
and the reviewers had enormous conflicts of interest."
____________________________________________________
[ End of Extract ] ]


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
___________________________________________________


Dermatitis. 2008 May-Jun; 19(3): E10-1.
Formaldehyde, aspartame, and migraines: a possible connection.
Jacob SE, Stechschulte S.
Department of Dermatology and Cutaneous Surgery, University of Miami,
Miami, FL, USA.

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. PMID: 18627677


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;


Dermatitis. 2008 Jan-Feb;19(1):9-15.
Systemic contact dermatitis.
Jacob SE, Zapolanski T. tamar.zapolanski@gmail.com;
Department of Dermatology and Cutaneous Surgery, University of Miami,
Miami, FL, USA.

Systemic exposure to allergens resulting in a cutaneous eruption is
known as systemic contact dermatitis (SCD).

Once sensitization occurs, varying exposures to antigens via multiple
routes (including transepidermal routes, intravenous or intramuscular
routes, inhalation, and ingestion) can result in systemic flare.

This article highlights the different categories of common
contactants, metals, medications, and plants, exposure to which leads
to SCD.

A comprehensive approach that takes into account all possible routes
of exposure is essential in diagnosing SCD and in helping patients
successfully avoid their allergens. PMID: 18346390


"We present a case of a medical student who presented with
erythematous eczematoid plaques on her trunk and legs and fine
vesiculation of her scalp, 3 weeks after starting anatomy class.

Of note, she routinely washed her face and arms after leaving the
anatomy lab, but remained in her scrubs for the rest of the day.

Formaldehyde and Quaternium-15 positive reactions in the same patient.
[ photo ]"

"Our patient underscores the importance of appropriate patch testing
and education.

Once we identified the allergy to formaldehyde and quaternium-15, we
provided patient education materials regarding the common and not-so-
common locations of these chemicals and cross-reactors.

We also gave the patient information on avoidance and safe
alternatives (see Table 5).

Fortunately, with technical advances, this student completed the
anatomy section via electronic learning tools.

By avoiding formaldehyde, including anatomy lab, FRP in her shampoo
and cosmetics, and aspartame in her diet, this patient dramatically
improved.

As with all contact dermatitides, the mainstay of treatment for
allergic contact dermatitis is avoidance."

http://www.skinandaging.com/article/5158 Skin & Aging Journal
ISSN: 1096-0120 - Volume 13 - Issue 12_2005 -
December 2005 - Pages: 22 - 27

Allergen Focus:
Focus on T.R.U.E. Test Allergens #21, 13 and 18:
Formaldehyde and Formaldehyde-Releasing Preservatives
-- By Sharon E. Jacob, M.D., Tace Steele, B.A., [now MD] and Georgette
Rodriguez, M.D., M.P.H.


http://www.eczemacenter.org/eczema_center/meetfacultystaff.htm
[ photo ]

The Eczema Center
Rady Children's Hospital of San Diego
8010 Frost Street, Suite 602, San Diego, CA 92123
or call... (858) 966-6774

Sharon E. Jacob , MD
Dr. Sharon E. Jacob is Assistant Clinical Professor of Pediatrics and
Medicine (Dermatology) at the University of California, School of
Medicine and Rady Children's Hospital.
She earned her medical degree from the Temple University, and
completed dermatology training at the University of Miami and advanced
contact dermatitis training at New York University (NYU).
She has been board certified in dermatology.

Dr. Jacob's clinical interests include atopic and contact dermatitis
and education.
She is considered a national expert on chemical sensitivities in the
skin and has published more than 45 journal articles, book chapters
and abstracts on this topic.
In 2005, Dr Jacob was the first to present contact dermatitis data on
U.S. pediatric patients to the American Contact Dermatitis Society
(ACDS).

She has received an excellence in teaching award from the University
of Miami Dermatology and the Clinical Research Award from the ACDS.
She is an active reviewer for the following medical publications
including Journal of the American Academy of Dermatology, Pediatric
Dermatology, Dermatitis, and the Archives of Dermatology.
Dr. Jacob also serves on the medical board of the Inflammatory Skin
Disease Institute and the Skin and Aging Journal.

Dr. Jacob enjoys taking care of children and their families and is an
advocate for children's dermatologic health.


http://www.eczemacenter.org/eczema_center/index.htm

Atopic dermatitis (AD) -- better known as eczema -- is the most common
chronic skin disorder seen in infants and children.
In fact, the prevalence of this condition has risen dramatically
during the last three decades.
Currently, 15% to 20% of children in the United States are expected to
experience this condition sometime during their lifetime, compared to
7% around 1960.

The negative impact of eczema is profound and insidious.
It affects both the patient who suffers from it and that patient's
family members, and it does so on two important levels -- physical and
emotional.

Physical:

Inflamed, itchy rashes can involve any and all of the skin surfaces
and are frequently complicated by skin breakdown and bacterial, viral,
and fungal infections.

It is linked to the development of life-long allergic conditions,
including asthma, food allergies, and rhinitis.

Any level of AD is extremely uncomfortable and, at times, painful.
Individuals with moderate to severe disease report that eczema hugely
disturbs their sleep and impacts performance of daily activities,
including adverse effects on school, sports activities, work, and peer
relationships.

In studies, individuals with eczema reported more negative impact on
quality of life than those with insulin-dependent diabetes!

Emotional:

Patients and their families experience considerable emotional
distress, anxiety, and embarrassment because of people's response to
this illness.

In fact, the emotional scarring on both patient and family members may
outlast eczema's physical effects.

Parents especially suffer because it is difficult for children
experiencing this condition to understand that their parents cannot
make the torment go away.
The stress of caring for these children is even greater than parents
caring for a child with insulin-dependent diabetes.

Patients experience considerable discrimination and social isolation
because of this illness.
People often stare, shiver with disgust or step back in fear from
those who have this condition.
The end result for patients: A life-time of struggle with their sense
of worth and self esteem.


http://aad2008.omnibooksonline.com/data/papers/CRS-113-F.pdf lecture
with photos
___________________________________________________


similar levels of daily formaldehyde and formic acid, causes of birth
defects, come from cigarettes, aspartame, and dark wines and liquors
-- folic acid protects most people: Rich Murray 2008.07.15
http://rmforall.blogspot.com/2008_07_01_archive.htm
Tuesday, July 15, 2008
http://groups.yahoo.com/group/aspartameNM/message/1552


http://www.divine.ca/en/health-and-wellness/articles/c_16_i_3295/5-reasons-to-qu
it-smoking-1.html

"A smoker who goes through one pack a day will smoke 7,300 cigarettes
a year, inhaling the equivalent of nearly 1 gram of formaldehyde
(yikes!)."

That's about 2.5 mg daily formaldehyde intake for 20 cigarettes, over
the 2 mg USA FDA alarm level for formaldehyde in average 2 liters
daily drinking water, while a single 12 oz can of diet soda also
results in about 2 mg formaldehyde toxic products in the body,
including formic acid, a notorious cause of birth defects.

Dark wines and liquors usually supply even more methanol, which the
body always turns into formaldehyde and formic acid -- the major cause
of "morning after" hangovers.

High levels of folic acid, a safe, affordable vitamin in fruits and
vegetables, largely prevents formaldehyde and formic acid toxicity in
most people.

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.

Fully 11 % of aspartame is methanol -- 1,120 mg aspartame in 2 liters
diet soda, almost six 12-oz cans, gives 123 mg methanol (wood
alcohol). The methanol is immediately released into the body after
drinking .
Within hours, the liver turns much of the methanol into formaldehyde,
and then much of that into 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, accumulating in and affecting every tissue.

If only 10 % of the methanol is retained daily 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 drinking 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 liters of
water.


formaldehyde and formic acid 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

The FEMA trailers give about the same amount of formaldehyde and
formic acid daily as from a quart of dark wine or liquor, or two
quarts (6 12-oz cans) of aspartame diet soda, from their over 1 tenth
gram methanol impurity (one part in 10,000), which the body quickly
makes into formaldehyde and then formic acid -- enough to be the major
cause of "morning after" alcohol hangovers.

Methanol and formaldehyde and formic acid also result from many fruits
and vegetables, tobacco and wood smoke, heater and vehicle exhaust,
household chemicals and cleaners, cosmetics, and new cars, drapes,
carpets, furniture, particleboard, mobile homes, buildings, leather...
so all these sources add up and interact with many other toxic
chemicals.

methanol impurity in alcohol drinks [ and aspartame ] is turned into
neurotoxic formic acid, prevented by folic acid, re Fetal Alcohol
Syndrome, BM Kapur, DC Lehotay, PL Carlen at U. Toronto, Alc Clin Exp
Res 2007 Dec. plain text: detailed biochemistry, CL Nie et al.
2007.07.18: Murray 2008.02.24
http://rmforall.blogspot.com/2008_02_01_archive.htm
Sunday, February 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1524


opportunities re BA Magnuson, GA Burdock et al., Aspartame Safety
Evaluation 2007 Sept., Critical Reviews in Toxicology:
Rich Murray 2008.07.11
http://rmforall.blogspot.com/2008_07_01_archive.htm
Friday, July 11, 2008
http://groups.yahoo.com/group/aspartameNM/message/1550
___________________________________________________
[ End of Extract ]


"Of course, everyone chooses, as a natural priority, to enjoy peace,
joy, and love by helping to find, quickly share, and positively act
upon evidence 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://RMForAll.blogspot.com new primary archive

http://groups.yahoo.com/group/aspartameNM/messages
group with 134 members, 1,569 posts in a public archive

http://groups.yahoo.com/group/aspartame/messages
group with 1,145 members, 23,096 posts in public archive
___________________________________________________
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


rmforall
United States

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Posted By rmforall on 12/28/2008 7:27 AM
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unexamined cofactors re folic acid antagonist research include methanol (quickly turns into formaldehyde and then formic acid in humans) from tobacco and wood smoke, alcohol beverages, aspartame, demethylation of caffeine: Rich Murray
2008.12.01
http://rmforall.blogspot.com/2008_10_01_archive.htm
Monday, December 1, 2008
http://groups.yahoo.com/group/aspartameNM/message/1569


http://www.eurekalert.org/pub_releases/2008-12/cmaj-met112408.php

Public release date: 1-Dec-2008
Contact: Kim Barnhardt kim.barnhardt@cma.ca
613-731-8610 x2224
Canadian Medical Association Journal

Maternal exposure to folic acid antagonists increases risks

Exposure to folic acid antagonists during pregnancy is associated with a higher
risk of placenta-mediated adverse outcomes such as preeclampsia, placental
abruption, fetal growth restriction or fetal death reports a retrospective
cohort study published in CMAJ
http://www.cmaj.ca/press/pg1263.pdf .

Folic acid antagonists include a broad range of drugs used to treat epilepsy,
mood disorders, hypertension and infections. As approximately 50% of pregnancies
in industrialized countries like Canada are unplanned, there is a risk of
unintended exposure to these medications.

The study, conducted by researchers from Ottawa, Montreal, Saskatoon and Hunan,
China looked at 14,982 women who had taken folic acid antagonists one year prior
to delivery and 59,825 women who did not. Dr. Shi Wu Wen and co- researchers
found that maternal exposure to folic acid antagonists was associated with a
slightly higher risk of adverse pregnancy outcomes. They suggest re-classifying
some folic acid antagonists and recommend increased folic acid supplements for
women requiring folic acid antagonists during pregnancy.

In a related commentary http://www.cmaj.ca/press/pg1243.pdf , Dr. Joel Ray
suggests the research study presents some "thought-provoking findings, but the
results may not be ready for adoption by clinical practitioners or drug policy
makers." He cites some real concerns with the study design and the need for
clinically relevant finding as cautions about translating findings into
practice.


http://content.nejm.org/cgi/content/abstract/343/22/1608
abstract
http://content.nejm.org/cgi/content/full/343/22/1608
free full text
The New England Jouranal of Medicine
Volume 343: 1608-1614 November 30, 2000 Number 22

Folic Acid Antagonists during Pregnancy and the Risk of Birth Defects
Sonia Hernández-Díaz, M.D., Dr.P.H., Martha M. Werler, Sc.D., Alexander M.
Walker, M.D., Dr.P.H., and Allen A. Mitchell, M.D.

ABSTRACT

Background
Multivitamin supplementation in pregnant women may reduce the risks of
cardiovascular defects, oral clefts, and urinary tract defects in their infants.
We evaluated whether the folic acid component of multivitamins is responsible
for the reduction in risk by examining the associations between maternal use of
folic acid antagonists and these congenital malformations.

Methods
We assessed exposure to folic acid antagonists that act as dihydrofolate
reductase inhibitors and to certain antiepileptic drugs in 3870 infants with
cardiovascular defects, 1962 infants with oral clefts, and 1100 infants with
urinary tract defects and also in 8387 control infants with malformations the
risk of which is not reduced after vitamin supplementation. Mothers were
interviewed within six months after delivery about their medication use during
pregnancy.

Results
The relative risks of cardiovascular defects and oral clefts in infants whose
mothers were exposed to dihydrofolate reductase inhibitors during the second or
third month after the last menstrual period, as compared with infants whose
mothers had no such exposure, were 3.4 (95 percent confidence interval, 1.8 to
6.4) and 2.6 (95 percent confidence interval, 1.1 to 6.1), respectively. The
relative risks of cardiovascular defects, oral clefts, and urinary tract defects
after maternal exposure to antiepileptic drugs were 2.2 (95 percent confidence
interval, 1.4 to 3.5), 2.5 (95 percent confidence interval, 1.5 to 4.2), and 2.5
(95 percent confidence interval, 1.2 to 5.0), respectively. Use of multivitamin
supplements containing folic acid diminished the adverse effects of
dihydrofolate reductase inhibitors, but not that of antiepileptic drugs.

Conclusions
Folic acid antagonists, which include such common drugs as trimethoprim,
triamterene, carbamazepine, phenytoin, phenobarbital, and primidone, may
increase the risk not only of neural-tube defects, but also of cardiovascular
defects, oral clefts, and urinary tract defects. The folic acid component of
multivitamins may reduce the risks of these defects.

Source Information
From the Slone Epidemiology Unit, Boston University School of Public Health,
Brookline, Mass. (S.H.-D., M.M.W., A.A.M.); and the Department of Epidemiology,
Harvard School of Public Health, Boston (S.H.-D., A.M.W.).

Address reprint requests to Dr. Hernández-Díaz at the Slone Epidemiology Unit,
Boston University School of Public Health, 1371 Beacon St., Brookline, MA 02446,
or at shernan@bu.edu .
____________________________________________________



methanol impurity in alcohol drinks [ and aspartame ] is turned into
neurotoxic formic acid, prevented by folic acid, re Fetal Alcohol Syndrome,
BM Kapur, DC Lehotay, PL Carlen at U. Toronto, Alc Clin Exp Res 2007 Dec.
plain text: detailed biochemistry, CL Nie et al. 2007.07.18: Murray
2008.02.24
http://rmforall.blogspot.com/2008_02_01_archive.htm
Sunday, February 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1524


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.
____________________________________________________



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


Re: 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
http://rmforall.blogspot.com/2008_02_01_archive.htm
Wednesday, March 19, 2008
http://groups.yahoo.com/group/aspartameNM/message/1528


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
http://rmforall.blogspot.com/2008_02_01_archive.htm
Wednesday, March 19, 2008
http://groups.yahoo.com/group/aspartameNM/message/1528
_____________________________________________________


details on 6 epidemiological studies since 2004 on diet soda
(mainly aspartame) correlations, as well as 14 other mainstream
studies on aspartame toxicity since summer 2005: Murray 2007.11.18
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 14, 2007
http://groups.yahoo.com/group/aspartameNM/message/1490


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

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

Monte WC., Is your Diet Sweetener killing you? Fitness Life. 2007 Nov; 33:
31-33.
Monte WC., A Deadly Experiment. Fitness Life. 2007 Dec; 34: 38-42.
Monte WC., Bittersweet: Aspartame Breast Cancer Link. Fitness Life. 2008
Feb; 34: 21-22.

Article 1 http://www.thetruthaboutstuff.com/review1.shtml
Article 2 http://www.thetruthaboutstuff.com/review2.shtml
Article 3 http://www.thetruthaboutstuff.com/review3.shtml

http://www.thetruthaboutstuff.com/articles.shtml 223 references with
abstracts or full and partial texts
_____________________________________________________



ASE 3.3.1. "Exposure to Formaldehyde From Methanol in Aspartame

As is described later, methanol is metabolized to formaldehyde, which is rapidly
further metabolized."

"For example, the demethylation of the caffeine found in one cup of coffee
produces 30 mg of formaldehyde (Imbus, 1988)."

ASE 151. Imbus, H. R. (1988) A review of regulatory risk assessment with
formaldehyde as an example. Regulatory Toxicology and Pharmacology 8 , pp.
356-366. [ crossref ]

[ http://lib.bioinfo.pl/pmid:3905920 [ not in PubMed ]

J Allergy Clin Immunol. 1985 Dec; 76(6):831-40 3905920 (P,S,G,E,B)
Clinical evaluation of patients with complaints related to formaldehyde
exposure.
H R Imbus

Formaldehyde is a very widely used chemical in our present society and one with
which every physician has had a first-hand experience in his early days of
training in the anatomy laboratory. The National Institute of Occupational
Safety and Health lists 52 occupations that expose people to formaldehyde. In
recent years, however, the increasing use of formaldehyde resins in the
production of building materials such as particleboard and urea-formaldehyde
foam insulation has resulted in exposures of large numbers of people in
nonoccupational settings. Consumer products such as cosmetics, cigarettes,
textiles, furniture, draperies, and preservatives release formaldehyde. It is
present in the outdoor atmosphere from products of combustion and automobile
exhaust and likewise in the home from such things as gas cooking. These more
widespread and increased exposures have resulted in concern regarding potential
health effects. Therefore, it is likely that physicians have or will encounter
patients who wish evaluations of a present or potential health effect from
formaldehyde. This article is for the purpose of providing assistance in such
evaluation.
Mesh-terms: Acute Disease; Animals; Asthma :: chemically induced; Chronic
Disease; Dermatitis, Contact :: etiology; Drug Hypersensitivity :: diagnosis;
Drug Hypersensitivity :: etiology; Environmental Exposure; Formaldehyde ::
toxicity; Human; Mice; Occupational Diseases :: chemically induced;
Radioimmunoassay; Rats; Respiratory Function Tests; Respiratory Hypersensitivity
:: diagnosis; Skin Tests; Time Factors;

http://www.nclabor.com/osha/etta/indguide/ig31.pdf 38 page
A Guide to Formaldehyde 1988 July H. R. Imbus
Health & Hygiene, Inc.
420 Gallimore Dairy Road, Greensboro, NC 27409
910-655-1818
www.Health-Hygiene.com/

http://web.archive.org/web/19981205114939/health-hygiene.com/

Merger Information

Impact Health Services, Inc. Merged with Health & Hygiene/ELB

In June, 1998, Impact Health Services, Inc., was merged with U.S. HealthWorks,
parent company of Health & Hygiene/ELB. Impact Health Services is the largest
mobile testing company providing hearing and respiratory surveillance services
throughout the country. Founded in 1972, and operating out of Kansas City,
Missouri, Impact has grown to serve over 5,000 client sites in all the 48
continental United States.

Headquartered in Greensboro, North Carolina, Health & Hygiene/ELB, which was
merged with U.S. HealthWorks in 1996, is one of the country's largest safety and
health consulting companies offering consulting, training, products and services
in the areas of industrial hygiene, occupational safety and ergonomics,
training, occupational health, hearing conservation, respiratory surveillance,
and OSHA compliance.

As a result of the recent merger, Health & Hygiene/ELB and Impact Health
Services have been merged to form U.S. HealthWorks-Preventive Services Division.
U.S. HealthWorks has appointed Jeffrey C. Morrill, formerly CEO of Impact, as
President of the new Preventive Services Division, Susan Megerson, formerly
President of Impact, will be managing on-site testing operations, and Hank
Barnum, formerly Sr. V.P.-Operations of Health & Hygiene/ELB, will be managing
consulting operations.

Company Overview

U.S. HealthWorks-Preventive Services is the nation's largest training and
consulting firm assisting employers and employer associations with the safety
and health concerns of their workforce. We are now also the nation's largest
provider of on-site medical surveillance and training services. Our mission is
to reduce absenteeism and its inherent costs by helping to provide a workplace
free of injuries and illnesses.

This is accomplished by assisting with regulatory compliance programs (OSHA,
DOT, JCAHO, EPA, etc.) and other preventative measures such as training, loss
control, and elimination of substance abuse.

Workplace absenteeism due to injuries and illnesses represents an enormous cost
to employers in wages for the absent employee and replacement employee, medical
costs, workers compensation premiums, regulatory fines, legal expenses,
retraining and rehabilitation. U.S. HealthWorks-Preventive Services strives to
significantly reduce these costs by emphasizing preventative services and
products.
Services Include:

* Occupational Medicine
* Ergonomics Consultation
* Industrial Hygiene
* Hearing Conservation
* Respiratory Surveillance
* On-Site Medical Monitoring
-Audiometric Testing - Exclusive TTC -Test, Train Counsel approach
-Pulmonary Testing
-Medical Clearance for Respirator Use
-Respirator Fit Testing
* Health Management Software & Equipment
* Safety Services
* TIOSH -- Training Institute for Occupational Safety & Health
* Data Management
* On-Site Employee Training
* Customized Hearing Protection and Communication Devices
* Network of Occupational Health Clinics

420 Gallimore Dairy Road
Greensboro, NC 27409
Phone 336-665-1818
Fax 336-665-0847
Revised June 25, 1998 ]


From:

opportunities re BA Magnuson, GA Burdock et al., Aspartame Safety Evaluation
2007 Sept., Critical Reviews in Toxicology: Rich Murray 2008.07.11
http://rmforall.blogspot.com/2008_07_01_archive.htm
Friday, July 11, 2008
http://groups.yahoo.com/group/aspartameNM/message/1550

Bernadene A. Magnuson,
George A. Burdock,
John Doull,
Robert M. Kroes, [deceased]
Gary M. Marsh,
Michael W. Pariza,
Peter S. Spencer,
William J. Waddell,
Ronald Walker,
Gary Murray Williams.
"Aspartame: A Safety Evaluation Based on Current Use Levels, Regulations,
and Toxicological and Epidemiological Studies,"
Critical Reviews in Toxicology, 37(8), 629-727, 2007 Sept [415 references]

http://www.utoronto.ca/nutrisci/faculty/Magnuson/
Bernadene A. Magnuson, Ph.D.
Adjunct Associate Professor, Department of Nutritional Sciences
Senior Scientific and Regulatory Consultant, Cantox Health Science
International, 2233 Argentia Road, Suite 308, Mississauga, ON L5N 2X7
Tel: (905) 542 2900 Fax: (905) 542 1011 BMagnuson@cantox.com;
_____________________________________________________



"Of course, everyone chooses, as a natural priority, to enjoy
peace, joy, and love by helping to find, quickly share, and positively
act upon evidence 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://RMForAll.blogspot.com new primary archive

http://groups.yahoo.com/group/aspartameNM/messages
group with 133 members, 1,569 posts in a public archive

http://groups.yahoo.com/group/aspartame/messages
group with 1144 members, 23,083 posts in a public archive
_____________________________________________________
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

Last edited Dec 28, 2008, 9:43 AM by rmforall

rmforall
United States

Send PM
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Posted By rmforall on 12/28/2008 7:42 AM
Reply to this post Go to the top of the page
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


"Of course, everyone chooses, as a natural priority, to enjoy peace, joy, and love by helping to find, quickly share, and positively act upon evidence 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://RMForAll.blogspot.com new primary archive

http://groups.yahoo.com/group/aspartameNM/messages
group with 112 members, 1,490 posts in a public,
searchable archive


http://rmforall.blogspot.com/2007_09_01_archive.htm
Saturday, September 15, 2007
http://groups.yahoo.com/group/aspartameNM/message/1472
bias, omissions, incuriosity = opportunity, aspartame safety evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more, 2007 Sept, Ajinomoto funded 98 pages html [$ 32 781888262_content.pdf]: Murray 2007.09.15
////////////////////////////////////////////////////////////


[ This layman review gives detailed access to the gist of six
epidemiological studies since 2004, two in 2007, that show correlations of diet soda (largely aspartame) with health issues.

Probably studies of the correlations at the top 0.1 to 1.0 % level of use over periods of years by people in vulnerable groups are needed.

http://groups.yahoo.com/group/aspartameNM/message/1141
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.

In total, there are 19 mainstream studies about negative effects with aspartame since summer, 2005, listed in this review, included many about the detailed biochemistry involved. ]
////////////////////////////////////////////////////////////


http://RMForAll.blogspot.com September 21, 2007
http://groups.yahoo.com/group/aspartameNM/message/1475

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

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 500 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 reflected 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.

"We cannot exclude the possibility that higher aspartame consumption
than that observed in this study may be associated with an elevated risk
of hematopoietic or brain cancers."

http://cebp.aacrjournals.org/cgi/content/full/15/9/1654 free full text
http://cebp.aacrjournals.org/cgi/reprint/15/9/1654 free full text pdf

Cancer Epidemiology Biomarkers & Prevention Vol. 15, 1654-1659,
September 2006
© 2006 American Association for Cancer Research

Consumption of Aspartame-Containing Beverages and Incidence of
Hematopoietic and Brain Malignancies

Unhee Lim 1,
Amy F. Subar 2, subara@mail.nih.gov,
Traci Mouw 1,
Patricia Hartge 1,
Lindsay M. Morton 1,
Rachael Stolzenberg-Solomon 1,
David Campbell 3,
Albert R. Hollenbeck 4
and Arthur Schatzkin 1

1 Division of Cancer Epidemiology and Genetics,

2 Division of Cancer Control and Population Sciences, National Cancer
Institute, NIH, Department of Health and Human Services;

3 Information Management Services, Inc., Rockville, Maryland; and

4 AARP, Washington, District of Columbia

Requests for reprints: Amy Subar,
Division of Cancer Control and Population Sciences,
National Cancer Institute,
6130 Executive Boulevard, EPN 4005, Rockville, MD 20852-7344.
Phone: 301-594-0831; Fax: 301-435-3710. E-mail: subara@mail.nih.gov,

BACKGROUND:
In a few animal experiments, aspartame has been linked to hematopoietic
and brain cancers.

Most animal studies have found no increase in the risk of these or other
cancers.

Data on humans are sparse for either cancer.

Concern lingers regarding this widely used artificial sweetener.

OBJECTIVE:
We investigated prospectively whether aspartame consumption is
associated with the risk of hematopoietic cancers or gliomas (malignant
brain cancer).

METHODS:
We examined 285,079 men and 188,905 women ages 50 to 71 years in the
NIH-AARP Diet and Health Study cohort

Daily aspartame intake was derived from responses to a baseline
self-administered food frequency questionnaire that queried consumption
of four aspartame-containing beverages (soda, fruit drinks, sweetened
iced tea, and aspartame added to hot coffee and tea) during the past year.

Histologically confirmed incident cancers were identified from eight
state cancer registries.

Multivariable-adjusted relative risks (RR) and 95% confidence intervals
(CI) were estimated using Cox proportional hazards regression that
adjusted for age, sex, ethnicity, body mass index, and history of diabetes.

RESULTS:
During over 5 years of follow-up (1995-2000), 1,888 hematopoietic
cancers and 315 malignant gliomas were ascertained.

Higher levels of aspartame intake were not associated with the risk of
overall hematopoietic cancer
(RR for >/=600 mg/d, 0.98; 95% CI, 0.76-1.27),
glioma (RR for >/=400 mg/d, 0.73; 95% CI, 0.46-1.15;
P for inverse linear trend = 0.05),
or their subtypes in men and women.

CONCLUSIONS:
Our findings do not support the hypothesis that aspartame increases
hematopoietic or brain cancer risk. PMID: 16985027

"We cannot exclude the possibility that higher aspartame consumption
than that observed in this study may be associated with an elevated risk
of hematopoietic or brain cancers.

In the laboratory study with positive findings, animals were fed doses
starting from 4 mg up to 5,000 mg per kg body weight.

Significantly elevated lymphomas and leukemias were observed in female
rats fed 20 mg of aspartame and higher (e.g., 1,200 mg for humans
weighing 60 kg or 132 lb; refs. 13, 14).

The reported aspartame intake in our data ranged from 0 to 3,400 mg/d
with sparse numbers in the upper intake categories
(1,200 or 2,000 mg/d, which is equivalent to ~7 to 11 cans of soft
drinks daily) compared with the lowest categories,
and the associations were similarly null in both men and women."
////////////////////////////////////////////////////////////


http://RMForAll.blogspot.com October 12, 2007
http://groups.yahoo.com/group/aspartameNM/message/1479
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

"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."

Prev Med. 2007 Apr; 44(4): 305-10. Epub 2006 Dec 29.
Non-alcoholic beverage and caffeine consumption and mortality: the
Leisure World Cohort Study.
Paganini-Hill A, annliahi@usc.edu,
Kawas CH, ckawas@uci.edu,
Corrada MM. mcorrada@uci.edu,
Department of Preventive Medicine, Keck School of Medicine of the
University of Southern California, CA, USA.

OBJECTIVE:
To examine the effects of non-alcoholic beverage and caffeine
consumption on all-cause mortality in older adults.

METHODS:
The Leisure World Cohort Study is a prospective study of residents of a
California retirement community.

A baseline postal health survey included details on coffee, tea, milk,
soft drink, and chocolate consumption.

Participants were followed for 23 years (1981-2004).

Risk ratios (RRs) of death were calculated using Cox regression for 8644
women and 4980 men (median age at entry, 74 years) and adjusted for age,
gender, and multiple potential confounders.

RESULTS:
Caffeine consumption exhibited a U-shaped mortality curve.

Moderate caffeine consumers had a significantly reduced risk of death
(multivariable-adjusted RR = 0.94, 95 % CI: 0.89, 0.99 for 100-199 mg/day
and RR = 0.90, 95 % CI: 0.85, 0.94 for 200-399 mg/day
compared with those consuming <50 mg/day).

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).

Neither milk nor tea had a significant effect on mortality after
multivariable adjustment.

CONCLUSIONS:
Moderate caffeine consumption appeared beneficial in reducing risk of death.

Attenuation in the observed associations between mortality and intake of
tea and milk with adjustment for potential confounders suggests that
such consumption identifies those with other mortality-associated
lifestyle and health risks.

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. PMID: 17275898


Age Ageing. 2007 Mar; 36(2): 203-9.
Type of alcohol consumed, changes in intake over time and mortality: the
Leisure World Cohort Study.
Paganini-Hill A, Kawas CH, Corrada MM.
Department of Preventive Medicine,
Keck School of Medicine of University of Southern California, USA.
annliahi@usc.edu

BACKGROUND:
modifiable behavioural risk factors including smoking and alcohol
consumption are major contributing or actual causes of mortality.

OBJECTIVE:
to examine the effect of alcohol intake on all-cause mortality in older
adults.

Design and SETTING:
prospective population-based cohort study of residents of a California,
United States retirement community.

SUBJECTS:
8,877 women and 5,101 men (median age, 74 years) who in the early 1980s
completed a postal health survey incluing details on alcohol consumption.

METHODS:
participants were followed for 23 years (1981-2004) including two
follow-up questionnaires (in 1992 and 1998) asking about current alcohol
intake.

Age-adjusted and multivariate-adjusted risk ratios of death and 95 %
confidence intervals were calculated separately for men and women, using
proportional hazard regression.

RESULTS:
of the 8,644 women and 4,980 men with complete information on the
variables of interest and potential confounders,
6,930 women and 4,456 men had died (median age, 87 years).

Both men and women who drank alcohol had decreased mortality compared
with non-drinkers.

Those who drank two or more drinks per day had a 15 % reduced risk of death.

The reduced risk was not limited to one type of alcohol.

Stable drinkers (those who reported drinking both at baseline and
follow-up) had a significantly decreased risk of death compared with
stable non-drinkers.

Those who started drinking at follow-up also had a significantly lower risk.

Women who quit drinking were at increased risk of death.

CONCLUSION:
in elderly men and women, moderate alcohol intake exhibits a beneficial
effect on mortality.

Those who quit may do so for health reasons that affect mortality.
PMID: 17350977
////////////////////////////////////////////////////////////



" Analyses that used food frequency questionnaire data suggested that
intake of over 1 drink per day of either regular or diet soft drinks was
associated with a over 50% higher incidence of metabolic syndrome
compared with intake of under 1 soft drink per week.

" Although the association of high fructose corn syrup intake and
insulin resistance may be a contributory mechanism, 31 in the present
study, both regular and diet soft drinks appeared to pose similar
metabolic hazards,
which suggests that other factors may be operational. "

" The caramel content of both regular and diet drinks may be a potential
source of advanced glycation end products, 5 which may promote insulin
resistance 36 and can be proinflammatory. 37 "

" It is conceivable, though,
that there may be residual confounding caused by lifestyle factors not
adjusted for in the present analyses. "

" As noted above, it is conceivable that residual confounding by
lifestyle/dietary factors not adjusted for may have contributed to the
metabolic risks associated with soft drink intake. "

" The similar metabolic hazard posed by both regular and diet soft
drinks is noteworthy given the lack of calories in the latter; however,
other studies have also reported associations of diet soft drinks with
weight gain in boys 29 and with hypertension in adult women. 7 "

29. Berkey CS, Rockett HRH, Field AE, Gillman MW, Colditz GA.
Sugar-added beverages and adolescent weight change.
Obesity Res. 2004; 12: 778–788.[Abstract/Free Full Text]

7. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC.
Habitual caffeine intake and the risk of hypertension in women.
JAMA. 2005; 294: 2330–2335.[Abstract/Free Full Text]


http://circ.ahajournals.org/cgi/content/full/116/5/480 free full text
[ Extracts ]

doi:10.1161/CIRCULATIONAHA.107.689935
CLINICAL PERSPECTIVE
Circulation. 2007; 116: 480-488.
© 2007 American Heart Association, Inc.
Epidemiology

Circulation. 2007 Jul 31; 116(5): 480-8. Epub 2007 Jul 23.
Soft drink consumption and risk of developing cardiometabolic risk
factors and the metabolic syndrome in middle-aged adults in the community.
Ravi Dhingra, MD;
Lisa Sullivan, PhD;
Paul F. Jacques, PhD;
Thomas J. Wang, MD;
Caroline S. Fox, MD; foxca@nhlbi.nih.gov,
James B. Meigs, MD, MPH;
Ralph B. D’Agostino, PhD;
J. Michael Gaziano, MD, MPH;
Ramachandran S. Vasan, MD vasan@bu.edu,

From the National Heart, Lung, and Blood Institute’s Framingham Heart
Study (R.D., T.J.W., C.S.F., R.S.V.), Framingham, Mass;

Massachusetts Veterans Epidemiology Research and Information Center
(R.D., J.M.G.), VA Boston Healthcare System, Boston, Mass;

Division of Aging (R.D., J.M.G.), Brigham and Women’s Hospital, Harvard
Medical School, Boston, Mass; Alice Peck Day Memorial Hospital (R.D.),
Lebanon, NH;

Department of Biostatistics (L.S., R.B.D.), Boston University School of
Public Health, Boston, Mass;

Jean Mayer USDA Human Nutrition Research Center on Aging (P.F.J.), Tufts
University, Boston, Mass; Division of Cardiology (T.J.W.) and Department
of Medicine (J.B.M.), Massachusetts General Hospital, Harvard Medical
School, Boston, Mass;

National Heart, Lung, and Blood Institute (C.S.F.), Bethesda, Md;
Divisions of Preventive Medicine and Cardiovascular Medicine (J.M.G.),
Brigham and Women’s Hospital, Boston, Mass;

and Cardiology Section and the Department of Preventive Medicine and
Epidemiology (R.S.V.), Boston University School of Medicine, Boston, Mass.

Correspondence to Ramachandran S. Vasan, MD, Framingham Heart Study, 73
Mount Wayte Ave, Suite 2, Framingham, MA 01702-5803. vasan@bu.edu,

Received January 12, 2007; accepted May 15, 2007.

BACKGROUND:
Consumption of soft drinks has been linked to obesity in children and
adolescents, but it is unclear whether it increases metabolic risk in
middle-aged individuals.

METHODS AND RESULTS:
We related the incidence of metabolic syndrome and its components to
soft drink consumption in participants in the Framingham Heart Study
(6,039 person-observations, 3,470 in women; mean age 52.9 years) who
were free of baseline metabolic syndrome.

Metabolic syndrome was defined as the presence of over of the following:

waist circumference over 35 inches (women) or over 40 inches (men);
fasting blood glucose over 100 mg/dL;
serum triglycerides over 150 mg/dL;
blood pressure over 135/85 mm Hg;
and high-density lipoprotein cholesterol under 40 mg/dL (men)
or under 50 mg/dL (women).

Multivariable models included adjustments for age, sex, physical
activity, smoking, dietary intake of saturated fat, trans fat, fiber,
magnesium, total calories, and glycemic index.

Cross-sectionally, individuals consuming over 1 soft drink per day had a
higher prevalence of metabolic syndrome
(odds ratio [OR], 1.48; 95 % CI, 1.30 to 1.69)
than those consuming under 1 drink per day.

On follow-up (mean of 4 years), new-onset metabolic syndrome developed
in 765 (18.7 %) of 4095 participants consuming under 1 drink per day and
in 474 (22.6 %) of 2059 persons consuming over 1 soft drink per day.

Consumption of over 1 soft drink per day
was associated with increased odds of developing
metabolic syndrome (OR, 1.44; 95% CI, 1.20 to 1.74),
obesity (OR, 1.31; 95 % CI, 1.02 to 1.68),
increased waist circumference (OR, 1.30; 95 % CI, 1.09 to 1.56),
impaired fasting glucose (OR, 1.25; 95% CI, 1.05 to 1.48),
higher blood pressure (OR, 1.18; 95 % CI, 0.96 to 1.44),
hypertriglyceridemia (OR, 1.25; 95 % CI, 1.04 to 1.51), and
low high-density lipoprotein cholesterol
(OR, 1.32; 95 % CI 1.06 to 1.64).

CONCLUSIONS:
In middle-aged adults, soft drink consumption is associated with a
higher prevalence and incidence of multiple metabolic risk factors.
PMID: 17646581

Key Words: diabetes mellitus • metabolic syndrome • epidemiology •
obesity • risk factors • carbonated beverages

* Introduction

Several reports from the United States and Europe indicate increasing
consumption of soft drinks among children, adolescents, and adults over
the past 3 decades. 1,2

Many clinical studies have linked the rising consumption of soft drinks
to the present epidemic of obesity and diabetes mellitus among children
and adolescents 3–6 and to the development of hypertension in adults. 7

Furthermore, added sweeteners in soft drinks have been linked to an
increase in serum triglycerides levels in some reports 8,9 but not in
others. 10,11

The association of soft drink consumption with obesity and higher
insulin resistance has been attributed to multiple factors, including
greater caloric intake, the high fructose corn syrup content, 12 less
satiety and compensation, and a general effect of consuming refined
carbohydrates (see review by Drewnowski and Bellisle 13).

The aforementioned data raise the possibility that the consumption of
soft drinks can fuel metabolic derangements, including insulin
resistance, that can translate into a greater risk of developing
abdominal obesity, high triglyceride levels, low levels of high-density
lipoprotein cholesterol (HDL-C), elevated blood pressure, and impaired
glucose tolerance; this constellation of metabolic traits has been
collectively referred to as the metabolic syndrome. 14

Higher prevalence of the metabolic syndrome poses greater risk for
cardiovascular disease in the community, 15 although the independent
contribution of this entity to vascular risk beyond its components has
been questioned 16

In the present prospective investigation, we tested the hypothesis that
greater soft drink consumption increases the risk of developing
metabolic risk factors (alone and in combination [metabolic syndrome])
in middle-aged adults in the community.

Additionally, we evaluated whether metabolic risk varied on the basis of
consumption of sugar-sweetened ("regular") versus artificially sweetened
("diet") soft drinks.

* Methods

Study Sample

The Framingham Heart Study began in 1948 with the enrollment of 5,209
participants into the original study cohort. 17

In 1971, children of the original cohort participants and the spouses of
the children were enrolled into the Framingham Offspring Study (n=5,124). 18

Offspring study participants are evaluated approximately every 4 years.

Information on daily consumption of soft drinks was collected via a
physician-administered questionnaire at each study visit from the fourth
(1987–1991) through the sixth (1995–1998) examination cycles.

That examination questionnaire did not elicit information regarding
consumption of regular versus diet soft drinks; however, such
information was available from the self-administered food frequency
questionnaires (FFQ; Willett questionnaire) 19 completed by participants
at the fifth (1992–1995) and sixth examination cycles (see below).

For the present investigation, we selected offspring cohort participants
who attended any 2 consecutive examinations from the fourth through the
seventh (1998–2001) examination cycles.

We excluded participants with missing data on covariates (n = 207) and
those with prevalent cardiovascular disease (n = 926).

After exclusions, a total of 8997 person-observations (4871 in women)
were eligible for the cross-sectional analyses.

For prospective analyses, we excluded individuals with baseline
metabolic syndrome (n = 2897 person-observations; metabolic syndrome as
defined below) and those with any missing metabolic syndrome components
on follow-up (n = 61 person-observations).

The schema for selection of individuals eligible for cross-sectional and
longitudinal analyses is displayed in the Figure.

All participants provided written informed consent, and the protocol for
the study was approved by institutional review board of Boston Medical
Center.

Figure 1185095

Selection of study sample from baseline examinations using the
examination cola questionnaire and from the sample with available FFQ
data (within parentheses, for examinations 5 and 6).
Eligible participants and exclusions are indicated in the Figure.
CVD indicates cardiovascular disease.

Measurement of Covariates

At each Framingham Heart Study examination, participants provided a
medical history and underwent a complete standardized physical
examination that included anthropometry, blood pressure measurements,
and laboratory assessment of vascular risk factors.

Fasting levels of blood glucose, triglycerides, and HDL-C were measured
with standard assays.

Blood pressure was measured by a physician using a mercury
sphygmomanometer and with the participant resting in a seated position
for 5 minutes; the average of 2 readings obtained on the participant’s
left arm constituted the examination blood pressure.

Physical activity was assessed by calculating a "physical activity
index"; participants were asked specific questions regarding how many
hours in a typical day they spent sitting, sleeping, or performing
light-moderate or heavy physical activities. 20

Alcohol intake was assessed by averaging the number of alcoholic
beverages consumed per week.

Participants who reported smoking 1 or more cigarettes per day in the
year before the Framingham Heart Study examination were considered
current smokers.

Assessment of Soft Drink Consumption and Dietary Intake of Other Foods

At the index examinations, participants reported the average number of
12-oz servings of soft drinks (Coke, Pepsi, Sprite, or other carbonated
soft drinks, separately categorized into caffeinated or decaffeinated
drinks) consumed per day in the year preceding the examination.

The responses to the questions were entered as integers (0 or more)
separately for caffeinated and decaffeinated soft drinks.

This questionnaire (referred to as the "examination cola questionnaire")
did not separate nondrinkers from infrequent drinkers (<1 drink per day).

Accordingly, we compared individuals who reported consuming 1, over 1,
or over 2 soft drinks per day with attendees who reported consuming
under 1 soft drink per day (infrequent drinkers and nondrinkers, who
served as the referent).

Intake of regular and diet soft drinks was assessed from FFQs 19 that
were administered at the fifth and sixth examinations.

We also assessed the dietary information on consumption of total
calories, saturated fat, trans fat, fiber, magnesium, and glycemic index
from the FFQ. 19

Because a FFQ was not administered at the fourth examination cycle,
dietary covariate data from the fifth examination cycle were used for
analyses using information from the examination cola questionnaire at
all 3 examinations.

Data from the FFQ were considered valid only if total energy intakes
reported were over 2.51 MJ/d (600 kcal/d) for men and women but under
17.54 MJ/d (4200 kcal/d) for men or under 16.74 MJ/d (4000 kcal/d) for
women and if fewer than 13 food items were left blank.

Each food item was categorized in 9 categories that ranged from never or
under 1 serving per month to over 6 servings per day.

For assessment of saturated fat, trans fat, or dietary fiber, the
nutrient intakes from all specific food items were multiplied by the
frequency of consumption.

The validity of the FFQ has been demonstrated previously. 21

Definition and Components of the Metabolic Syndrome

The metabolic syndrome was considered present if 3 or more of the
following individual components were present 14,22:
waist circumference over 35 inches (88 cm) for
or over 40 inches (102 cm) for men;
fasting blood sugar over 100 mg/dL (5.5 mmol/L) or treatment with oral
hypoglycemic agents or insulin;
blood pressure over 135/85 mm Hg or treatment for hypertension;
serum triglycerides over 150 mg/dL (1.7 mmol/L)
or treatment for hypertriglyceridemia (with niacin or fibrates);
and HDL-C under 40 mg/dL (1.03 mmol/L) in men
or under 50 mg/dL (1.3 mmol/L) in women.

Statistical Analyses

Age- and sex-adjusted baseline characteristics of the participant groups
defined according to the number of soft drinks consumed in 1 day
(under 1, 1, or over 2 per day) were compared by multiple linear and
multiple logistic regression analysis for continuous and categorical
characteristics, respectively.
Data on consumption of soft drinks at each of the 3 eligible baseline
examinations (examination cola questionnaire) were used for this purpose.
Tests for trend in baseline characteristics across soft drink
consumption categories were performed with multiple regression.
We also assessed the baseline characteristics after excluding
participants with prevalent metabolic syndrome at baseline
examinations (sample used for incidence analyses; see below).

Soft Drink Consumption and Prevalence of the Metabolic Syndrome

We used data from examinations 4, 5, and 6 (examination cola
questionnaire) and generalized estimating equations to compare the
prevalence of metabolic syndrome in participants who consumed over 1
soft drink per day with those who consumed under 1 soft drink per day
(referent).
Each participant could contribute up to 3 person-examinations of data
for analysis.
We also evaluated a dose response by comparing individuals
who consumed 1 soft drink per day and those who consumed over 2 soft
drinks per day with the referent group.
We constructed multivariable models in hierarchical fashion with
adjustment for age and sex (model I)
and for age, sex, physical activity index, smoking, dietary consumption
of saturated fat, trans fat, fiber, magnesium, total calories, and
glycemic index (model II).

We used soft drink consumption data from FFQs at examinations 5 and 6,
which yielded a smaller sample (Figure), to relate the prevalence of
metabolic syndrome across the following categories of intake of regular
versus diet soft drinks using generalized estimating equations:
(1) under 1 diet or regular soft drink per week (referent),
(2) 1 to 6 diet soft drinks per week,
(3) over 1 diet soft drink per day,
(4) 1 to 6 regular soft drinks per week,
(5) 1 to 6 regular or diet soft drinks per week,
and (6) over 1 regular soft drink per day.
Individuals reporting consumption of both diet and regular soft drinks
over 1/d (n = 16) were grouped into the last category empirically.
We evaluated the 2 sets of models (I and II) noted above.

Soft Drink Consumption and Incidence of the Metabolic Syndrome

To assess the relations of soft drink consumption to the incidence of
metabolic syndrome, we excluded participants with prevalent metabolic
syndrome at each of examination cycles 4, 5, and 6 (n = 2,897
person-observations).
Then, we used pooled logistic regression analyses
by combining each 4-year follow-up period of observations to relate the
number of soft drinks consumed per day (examination cola questionnaire)
to the incidence of metabolic syndrome (from examination cycles 4 to 5,
5 to 6, and 6 to 7).23
The eligible participants were free of metabolic syndrome
at each baseline examination,
and in this setting, pooled logistic regression has been shown to
provide risk estimates similar to time-dependent Cox models.24
We compared the consumption of soft drinks over 1 per day with
infrequent drinkers (under 1 per day; referent) and also
tested for a dose response by comparing groups consuming 1 and over 2
soft drinks per day with the referent group.
We evaluated 2 sets of models
(covariates as in models I and II above),
which paralleled the analyses of prevalence of metabolic syndrome.

Consumption of soft drinks varies with age and by sex.25
It has also been suggested that the effects of soft drinks and
carbohydrates on metabolic traits may vary according to age, sex,26
and baseline body weight.27
Therefore, we assessed for effect modification by age (modeled
as a continuous variable), sex, and body mass index
(under 30 versus over 30 kg/m2) by incorporating appropriate interaction
terms in the multivariable models.
We repeated analyses with additionally adjustment
for alcohol consumption and baseline levels of systolic and diastolic
blood pressure, blood glucose, serum triglycerides, and HDL-C.
These models were constructed to account for baseline levels of
metabolic traits.
Additionally, we repeated analyses to examine the association
between consumption of caffeinated and decaffeinated soft drinks,
considered separately, and incidence of the metabolic syndrome.
Because individuals with diabetes mellitus are a particularly high-risk
group for developing metabolic abnormalities, we also repeated our
analyses after excluding those with prevalent diabetes mellitus at baseline.

To compare the risk of new-onset metabolic syndrome according to the
type of soft drink consumed (regular versus diet),
we used data from the FFQs at examinations 5 and 6
and evaluated the incidence of the metabolic syndrome across categories
of soft drinks consumed.
The 6 categories of regular and diet soft drinks were those noted above
(for the analyses of the prevalence of metabolic syndrome),
and 2 sets of models were evaluated
(models I and II, as described above).

Incidence of Individual Components of Metabolic Syndrome

We used multivariable logistic regression to evaluate the relations of
soft drink consumption to the incidence of each individual component of
metabolic syndrome using data from the examination cola questionnaire.
We excluded participants who had the specific metabolic trait prevalent
at baseline; for example, we excluded individuals with blood glucose
over 100 mg/dL (5.5 mmol/L) from the "at-risk" group for analysis that
examined the incidence of impaired fasting glucose.
Thus, we examined the incidence of increased waist circumference,
impaired fasting glucose, high blood pressure, hypertriglyceridemia, and
low HDL-C (all defined as above) according to the number of soft drinks
consumed per day.

We evaluated 2 sets of models (I and II, as noted above) and compared
the risk of developing metabolic traits associated with consumption of
over 1 soft drinks per day
with that in infrequent drinkers (under 1 soft drinks per day).
We also evaluated for a dose response as detailed above.
We did not perform analyses of development of individual metabolic
syndrome components in relation to regular versus diet soft drink intake
using the FFQ data at examinations 5 and 6 because the grouping of
incident events into 6 categories resulted in modest numbers of events
in each category.

All analyses were performed with SAS software version 9.0 (SAS
Institute, Cary, NC). A 2-sided probability value of under 0.05 was
considered statistically significant.

The authors had full access to and take full responsibility for the
integrity of the data. All authors have read and agree to the manuscript
as written.

Results

The baseline characteristics of participants according to the categories
of soft drinks consumed per day are presented in Table 1.

Approximately 35 % of the participants reported consuming over 1 soft
drink per day in response to the examination cola questionnaire
(data based on all 3 examinations).

In comparison, only 22 % of participants reported intake of at least 1
soft drink (diet or regular) per day in response to the FFQ (data
available for examinations 5 and 6 only).

The lower proportion reporting daily intake on the FFQ may be related to
the greater number of options available to indicate soft drink intake;
participants drinking 1 to 6 soft drinks per week (also 22 % on the FFQ)
may have rounded their responses on the examination cola questionnaire
to the nearest integer.

View this table:

TABLE 1. Baseline Characteristics of Participants According to
Soft Drink Consumption (n = 8997)

In age- and sex-adjusted models, the prevalence of obesity (assessed
both by body mass index and by waist circumference), high blood
pressure, glucose intolerance, low HDL-C, and hypertriglyceridemia was
significantly higher in those who consumed a greater number of soft
drinks per day.

Serum total cholesterol, low-density lipoprotein cholesterol, physical
activity index, and alcohol consumption did not vary across categories
of soft drinks consumed.

Similar trends were obtained when we excluded individuals with prevalent
metabolic syndrome (Data Supplement, Table I).

Prevalence of the Metabolic Syndrome

There was a 48 % higher adjusted prevalence of metabolic syndrome among
those who consumed 1 or more soft drinks per day relative to individuals
with infrequent soft drink consumption (Table 2).

We observed a rising prevalence of metabolic syndrome across categories
of 1 and over 2 soft drinks per day

In parallel analyses with the data from the FFQ (Table 2), participants
who consumed over 1 diet or regular soft drink per day had nearly a
1.8-fold adjusted prevalence of metabolic syndrome compared with
infrequent drinkers (under 1 per week).

TABLE 2. Cross-Sectional Relationships of Soft Drink Consumption With
Prevalence of Metabolic Syndrome

Incidence of the Metabolic Syndrome

Individuals who consumed at least 1 soft drink per day had a 44 % higher