Can Diet Soda and Sugarless Gum Cause Cancer?

*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1237
ubiquitous potent uncontrolled co-factors in nutrition research are
formaldehyde from wood and tobacco smoke and many sources,
including from methanol in dark wines and liquors, in pectins
in fruits and vegetables, and in aspartame:
Murray 2006.01.13, more 2006.02.14

February 14, 2006 Dear Prof. David L. Katz and colleagues,

It is with great respect and appreciation that I looked over your fine
work in the public media, the Yale-Griffin Hospital
Prevention Research Center, and the Integrative Medicine Center,
after viewing your comments on Monday, February 13 on ABC
with Diane Sawyer for 4 minutes:

http://www.abcnews.go.com/GMA/Health/story?id=1611955&page=1

re the NY Times article, a full newspaper page, on February 12:

http://www.nytimes.com/2006/02/12/business/yourmoney/12sweet.html?_r=1&oref=slogin

I cite key mainstream research findings that clarify essential facts,
which can motivate effective action to alleviate gratuitous suffering.

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, 37 mg,
is 18.5 times the USA EPA limit for daily formaldehyde in
drinking water, 2.0 mg in 2 L average daily drinking water.

Dark wines and liquors, as well as aspartame, provide
similar levels of methanol, above 100 mg daily, for
long-term heavy users, 2 L daily, about 6 cans.

Methanol is inevitably largely turned into formaldehyde,
and thence largely into formic acid.
It is the major cause of the dreaded symptoms of "next
morning" hangover.

Any unsuspected source of methanol, which the body always quickly
and largely turns into formaldehyde and then formic acid, must be
monitored, especially for high responsibility occupations, often with
night shifts, such as pilots and nuclear reactor operators.

In particular, the next review gives many recent mainstream
peer-reviewed studies that show formaldehyde,
always inevitably derived in the body from any methanol source,
including aspartame, causes endothelial injury,
ie, diabetic neuropathy -- among the most serious and complex
complications of diabetes.

http://groups.yahoo.com/group/aspartameNM/message/1263
many studies on endothelial injury (diabetic neuropathy) by adducts of
formaldehyde derived from methylamine from many of the same sources
as also supply methanol (formaldehyde), including aspartame:
PH Yu et al: DJ Conklin et al: Murray 2005.12.04

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text Trocho & Alemany 1998.06.26
Universitat Autònoma de Barcelona : Murray 2002.12.22

http://groups.yahoo.com/group/aspartameNM/message/1250
aspartame causes cancer in rats at levels approved for humans,
Morando Soffritti et al, Ramazzini Foundation, Italy &
National Toxicology Program
of National Institute of Environmental Health Sciences
2005.11.17 Env. Health Pers. 35 pages: Murray

http://groups.yahoo.com/group/aspartameNM/message/1291
European Food Safety Authority to decide aspartame safety by May:
caffeine diet drinks cause female hypertension, WC Winkelmayer et al,
JAMA 2005.11.09: PubMed lists 50 items for "diet soft drinks" since
2004 Oct.: Murray 2006.01.24

As a medical layman, I suggest that evidence mandates immediate
exploration of the role of these ubiquitious, potent formaldehyde
sources as co-factors in epidemiology, research, diagnosis,
and treatment in a wide variety of disorders.

Folic acid, from fruits and vegetables, plays a role by powerfully
protecting against methanol (formaldehyde) toxicity.

Many common drugs, such as aspirin, interfere with folic acid,
as do some mutations in relevant enzymes.

The majority of aspartame reactors are female.

In mutual service, Rich Murray
*******************************************************

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and act upon the facts
about healthy and safe food, drink, and environment."

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

http://groups.yahoo.com/group/aspartameNM/messages
group with 151 members, 1,302 posts in a public, searchable archive
http://RmForAll.blogspot.com http://AspartameNM.blogspot.com

Dark wines and liquors, as well as aspartame, provide
similar levels of methanol, above 100 mg daily, for
long-term heavy users, 2 L daily, about 6 cans.

Methanol is inevitably largely turned into formaldehyde,
and thence largely into formic acid.
It is the major cause of the dreaded symptoms of "next
morning" hangover.

185 times the New Jersey limit,
615 times the California and Maine limits,
1850 times the Maryland limit.

The 1999 July EPA 468-page formaldehyde profile admits that
four states substantially exceed the federal EPA limit:

Environmental Protection Agency 2.00 mg in 2 L daily
drinking water

California and Maine------------ 0.06 mg
Maryland---------------------- 0.02 mg
New Jersey-------------------- 0.20 mg

http://groups.yahoo.com/group/aspartameNM/message/1108
faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of
Bialystok, Poland, abstracts -- ethanol, methanol,
formaldehyde, formic acid, acetaldehyde, lipid peroxidation,
green tea, aging: Murray 2004.08.08 2005.07.11

http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July
1999: Murray 2002.05.30 rmforall
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1106
hangover research relevant to toxicity of 11% methanol in aspartame
(formaldehyde, formic acid): Calder I (full text): Jones AW:
Murray 2004.08.05 rmforall

Since no adaquate data has ever been published on the exact disposition
of toxic metabolites in specific tissues in humans of the 11% methanol
component of aspartame, the many studies on morning-after hangover
from the methanol impurity in alcohol drinks are the main available
resource to date.

Jones AW (1987) found next-morning hangover from red wine with
100 to 150 mg methanol
(9.5% w/v ethanol, 100 mg/l methanol, 0.01%,
one part in ten thousand).

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) --
the same amount that produces hangover from red wine.

The expert review by Monte WC (1984) states:
"An alcoholic consuming 1500 calories a day from alcoholic sources
alone may consume between 0 and 600 mg of methanol each day
depending on his choice of beverages (Table 1)...."
Table 1 lists red wine as having 128 mg/l methanol,
about one part in ten thousand.

An editorial review by Ian Calder, F.R.C.A.,
"Hangovers: not the ethanol-- perhaps the methanol",
British Medical Journal 1997 Jan 4; 314(7073): 2
[Tel/Fax: 0171 720 9279
Consultant Anaesthetist at the National Hospital
for Neurology and Neurosurgery, London WCIN 3BG, UK]
http://bmj.bmjjournals.com/search.dtl search to get free full text ],
states:

"In fact, ethanol itself may play only a minor part in producing the thirst,
headache, fatigue, nausea, sweating, tremor, remorse, and anxiety that
hangover sufferers report.... [ Also, dizziness is common. ]

"Between a quarter and a half of drinkers claim not to experience
hangover symptoms despite having been intoxicated. (three citations)"

The symptom list is similar to reports by aspartame reactors.

If only a fraction of aspartame users happen to be vulnerable to the
methanol, that would account well for the disbelief by those who are
not aspartame reactors, as well as the scientific difficulty in proving
aspartame toxicity in the general population.

Research can study whether the hangover prone are also vulnerable to
aspartame, methanol, formaldehyde, and formic acid, and determine
the specific biochemistry for different groups.

Hangover treatments may help aspartame reactors. For instance,
adaquate folic acid (folate) helps humans eliminate the toxic products
from methanol.

Reprod Toxicol. 1996 Nov-Dec; 10(6): 455-63.
Influence of dietary folic acid on the developmental toxicity of methanol
and the frequency of chromosomal breakage in the CD-1 mouse.
Fu SS, Sakanashi TM, Rogers JM, Hong KH, Keen CL.
Department of Nutrition, University of California, Davis 95616, USA.

"These results show that marginal folate deficiency in pregnant dams
significantly increases the teratogenicity of MeOH." PMID: 8946559

There are no reports of hangover from heavy use of orange juice,
34 mg/l methanol, since the methanol in many fruits and vegetables
is locked up in complex pectin molecules,
not released by human digestion. (Monte WC 1984)

I've never found any reports by aspartame reactors,
who are often sensitive even to a single breath mint
or stick of chewing gum (0.4 to 0.8 mg methanol),
of having the same symptoms from fruits or vegetables.

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

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

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 2003.12.31 Mark Sherman, AP writer:
Robert Swift, MD [ formaldehyde from methanol in aspartame ]:
Murray 2004.01.16 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 2004.01.18

http://groups.yahoo.com/group/aspartameNM/message/1099
Diagnose-Me.com: formaldehyde from 11 % methanol part
of aspartame: recent abstracts for methanol and hangovers:
Murray 2004.07.10

http://bmj.bmjjournals.com/search.dtl search to get free full text
British Medical Journal 1997 (4 January); 314(7073): 2.
Ian Calder, F.R.C.A. [ Tel/Fax: 0171 720 9279
Consultant Anaesthetist at
the National Hospital for Neurology and Neurosurgery,
London WCIN 3BG, UK ]

Editorials Hangovers: Not the ethanol - perhaps the methanol

"Wine is only sweet to happy men," wrote an unhappy John Keats to
his sweetheart.(1) His observation seems to have been vindicated.

Harburg et al found that psychosocial factors such as guilt about
drinking, a neurotic personality, becoming angry or depressed while
drinking, and having suffered "negative life events"
in the past 12 months are better predictors of symptoms
of hangover than the amount of ethanol drunk.(2)

In fact, ethanol itself may play only a minor part in producing the thirst,
headache, fatigue, nausea, sweating, tremor, remorse, and anxiety that
hangover sufferers report.
Hangover symptoms are worst at a time when almost all ethanol and its
metabolite acetaldehyde have been cleared from the blood,
and peak blood ethanol or acetaldehyde levels are not related to the
severity of hangover.(3 )

Between a quarter and a half of drinkers claim not to experience
hangover symptoms despite having been intoxicated.(2, 3, 4)

Congeners -- complex organic molecules such as polyphenols,
higher alcohols including methanol, and histamine,
which occur in varying amounts in ethanolic drinks -- are
probably more to blame than ethanol.

Chapman found that hangover symptoms were almost twice as
common in volunteers who drank 1.5 ml/kg [ body weight ]
of bourbon whiskey -- which has methanol concentrations of 26 mg/l --
as in those drinking the same dose of vodka
( 3.9 mg of methanol per litre ). (5)
[For a 60 kg person, this would be 90 mg bourbon, 0.09 l,
giving 2.34 mg methanol, which led to twice
as many symptoms as the 0.35 mg methanol from vodka.
The bourbon gave as about as much methanol as an ounce of diet soda.]

Pawan compared the hangover produced by different types of drink
(but only one brand of each) in his study of 20 volunteers.
The severity of hangover symptoms declined in the order of brandy,
red wine, rum, whisky, white wine, gin, vodka, and pure ethanol.(6)
Vodka and pure ethanol caused only mild headaches in two volunteers.

Jones has suggested that it is the metabolism of methanol to
formaldehyde and formic acid that causes symptoms of hangover,
with quicker methanol metabolisers suffering more.(7)
The justification for this suggestion is threefold:
the types of drink associated with more severe hangovers
contain higher levels of methanol;
the time course of methanol metabolism corresponds
to the onset of symptoms;
and a small dose of ethanol,
which blocks the formation of formaldehyde and formic acid,
provides an effective treatment for hangovers
("the hair of the dog").

The economic and social consequences of hangovers are probably
considerable but difficult to quantify.
Performance accuracy is impaired synergistically by sleep deprivation
and hangover.(8)
Drivers perform less well in simulators when tested the morning after
drinking ethanol.(9)
Making driving with a hangover a criminal offence might be logical,
but is probably impractical in the absence of a simple diagnostic test
like breath alcohol.

Many pathophysiological disturbances occur during hangover,
including dehydration; metabolic acidosis; hypoglycaemia; disturbed
prostaglandin synthesis; abnormal secretion of vasopressin, cortisol,
aldosterone, renin, and testosterone; increased cardiac output;
tachycardia; and vasodilatation.

Hypoglycaemia and acidosis can be treated with fructose or glucose,(9)
and the cardiovascular abnormalities with ß blockade,(10)
but symptoms are not alleviated.
However, rehydration and anti-inflammatory analgesics are helpful,
particularly if treatment is started before bedtime.(11)

A completely effective treatment is probably unattainable (since so
many factors -- such as lack of sleep, active or passive smoking,
dietary indiscretions, unaccustomed physical activity,
intermittent upper airway obstruction, and emotional disturbances --
must play a part)
and is arguably undesirable since the fear of hangover prompts most
people to moderate their ethanol intake.(4 )

Even moderate amounts of ethanol can be damaging,(12) so a penalty
for consumption is in our interests. Perhaps those who aspire to be
one of Dr Johnson's "heroes" by drinking brandy (13)
are sensible as well as brave.

Ian Calder, Consultant anaesthetist, Department of Neuroanaesthesia,
National Hospital for Neurology and Neurosurgery,
Queen Square, London WC1N 3BG UK

1. Keats J. Letter to Fanny Brawne. In: Tripp RT, ed. The international
thesaurus of quotations. England: Penguin, 1976: 266.

2. Harburg E, Gunn R, Gleiberman L, DiFranceisco W, Schork A.
Psychosocial factors, alcohol use and hangover signs
among social drinkers: a reappraisal.
J Clin Epidemiol 1993; 46: 413-22. [Medline]

3. Ylikahri RH, Huttunen M, Eriksson CJ, Nikkila EA.
Metabolic studies on the pathogenesis of hangover.
Eur J Clin Invest 1974; 4: 93-100.

4. Smith CM, Barnes GM.
Signs and symptoms of hangover; prevalence and relationship
to alcohol use in a generally adult population.
Drug Alcohol Depend 1983; 11: 249-69. [Medline]

5. Chapman LF.
Experimental induction of hangover.
Q J Stud Alcohol 1970; 5: 67-85. [Medline]

6. Pawan GLS.
Alcoholic drinks and hangover effects.
Proc Nutr Soc 1973; 32: 15A.

7. Jones AW.
Elimination half-life of methanol during hangover.
Pharmacol Toxicol 1987; 60; 217-20.

8. Peeke SC, Callaway E, Jones RT, Stone GC, Doyle J.
Combined effect of alcohol and sleep deprivation in normal young adults.
Psychopharmacol 1980; 67: 279-87. [Medline]

9. Seppala T, Leino T, Linnoila M, Huttunen MO, Ylikahri RH.
Effects of hangover on psychomotor skills related to driving: modification
by fructose and glucose.
Acta Pharmacol Toxicol 1976; 38: 209-18.

10. Bogin RM, Nostrant TT, Young MJ.
Propranolol for the treatment of the alcoholic hangover.
Am J Drug Alcohol Abuse 1986; 12: 279-84.

11. Khan MA, Jensen K, Krogh HJ.
Alcohol induced hangover. A double blind comparison
of pyritinol and placebo in preventing hangover symptoms.
Q J Stud Alcohol 1973; 34: 1195-201. [Medline]

12. Karhunen PJ, Erkinjuntti T, Laippala P.
Moderate alcohol consumption and loss of cerebellar Purkinje cells.
BMJ 1994; 308: 1663-7.

13. Boswell J.
Life of Johnson. April 7th 1779. Oxford University Press: Oxford, 1970.

This article has been cited by other articles:

M. H. Pittler, A. R. White, C. Stevinson, and E. Ernst.
Effectiveness of artichoke extract in preventing alcohol-induced hangovers:
a randomized controlled trial
Can. Med. Assoc. J., December 9, 2003; 169(12): 1269 - 1273.
[Abstract] [Full Text] [PDF]

W. T Thompson, M. E Cupples, C. H Sibbett, D. I Skan, and T. Bradley.
Challenge of culture, conscience, and contract to general practitioners'
care of their own health: qualitative study
BMJ, September 29, 2001; 323(7315): 728 - 731.
[Abstract] [Full Text] [PDF]

"Systemic methanol is extensively metabolized
by liver alcohol dehydrogenase and catalase-peroxidase enzymes to
formaldehyde,
which is in turn rapidly oxidized to formic acid
by formaldehyde dehydrogenase enzymes
(Goodman and Tephly, 1968; Heck et al., 1983; Røe, 1982;
Tephly and McMartin, 1984)."

"That substantial amounts of methanol metabolites or by-products are
retained for a long time is verified by Horton et al. (1992)
who estimated that 18 h following an iv injection of 100 mg/kg
of 14C-methanol in male Fischer-344 rats,
only 57% of the dose was eliminated from the body.

From the data of Dorman et al. (1994)
and Medinsky et al. (1997),
it can further be calculated that 48 h
following the start of a 2-h inhalation exposure
to 900 ppm of 14C-methanol vapors in female cynomolgus monkeys,
only 23% of the absorbed 14C-methanol
was eliminated from the body.

These findings are corroborated by the data of Heck et al. (1983)
showing that 40% of a 14C-formaldehyde inhalation dose
remained in the body 70 h postexposure."

"Exposure to methanol also results from the consumption of certain
foodstuffs (fruits, fruit juices, certain vegetables, aspartame sweetener,
roasted coffee, honey) and alcoholic beverages
(Health Effects Institute, 1987; Jacobsen et al., 1988)."

"However, the severe toxic effects are usually associated with the
production and accumulation of formic acid,
which causes metabolic acidosis and visual impairment
that can lead to blindness and death at blood concentrations
of methanol above 31 mmol/l
(Røe, 1982; Tephly and McMartin, 1984; U.S. DHHS, 1993).

Although the acute toxic effects of methanol in humans
are well documented, little is known
about the chronic effects of low exposure doses,
which are of interest in view of the potential use of methanol
as an engine fuel and current use as a solvent and chemical intermediate.

Gestational exposure studies in pregnant rodents (mice and rats)
have also shown that high methanol inhalation exposures
(5000 or 10,000 ppm and more,
7 h/day during days 6 or 7 to 15 of gestation) can induce birth defects
(Bolon et al., 1993; IPCS, 1997; Nelson et al., 1985)."

"The corresponding average elimination half-life of absorbed methanol
through metabolism to formaldehyde
was estimated to be 1.3, 0.7-3.2, and 1.7 h."

"Inversely, in monkeys and in humans, a larger fraction of body burden
of formaldehyde is rapidly transferred to a long-term component.
The latter represents the formaldehyde that (directly or after oxidation
to formate) binds to various endogenous molecules..."

"Animal studies have reported that systemic methanol is eliminated
mainly by metabolism (70 to 97% of absorbed dose)
and only a small fraction is eliminated as unchanged methanol in urine
and in the expired air (< 3-4%)
(Dorman et al., 1994; Horton et al., 1992).

Systemic methanol is extensively metabolized
by liver alcohol dehydrogenase and catalase-peroxidase enzymes to
formaldehyde,
which is in turn rapidly oxidized to formic acid
by formaldehyde dehydrogenase enzymes
(Goodman and Tephly, 1968; Heck et al., 1983; Røe, 1982;
Tephly and McMartin, 1984).

Under physiological conditions, formic acid dissociates to formate and
hydrogen ions.

Current evidence indicates that, in rodents, methanol is converted
mainly by the catalase-peroxidase system
whereas monkeys and humans metabolize methanol
mainly through the alcohol dehydrogenase system
(Goodman and Tephly, 1968; Tephly and McMartin, 1984).

Formaldehyde, as it is highly reactive, forms relatively stable adducts
with cellular constituents (Heck et al., 1983; Røe, 1982)."

"The whole body loads of methanol, formaldehyde, formate,
and unobserved by-products of formaldehyde metabolism were followed.

Since methanol distributes quite evenly in the total body water,
detailed compartmental representation of body tissue loads
was not deemed necessary."

"According to model predictions,
congruent with the data in the literature
(Dorman et al., 1994; Horton et al., 1992),
a certain fraction of formaldehyde is readily oxidized to formate,
a major fraction of which is rapidly converted to CO2 and exhaled,
whereas a small fraction is excreted as formic acid in urine.

However, fits to the available data in rats and monkeys
of Horton et al. (1992) and Dorman et al. (1994) show that,
once formed, a substantial fraction of formaldehyde
is converted to unobserved forms.

This pathway contributes to a long-term unobserved compartment.

The latter, most plausibly, represents either the formaldehyde that
(directly or after oxidation to formate) binds to various endogenous
molecules (Heck et al., 1983; Røe, 1982)
or is incorporated in the tetrahydrofolic-acid-dependent one-carbon
pathway to become the building block of a number
of synthetic pathways (Røe, 1982; Tephly and McMartin, 1984).

That substantial amounts of methanol metabolites or by-products
are retained for a long time is verified by Horton et al. (1992)
who estimated that 18 h following an iv injection of 100 mg/kg of
14C-methanol in male Fischer-344 rats,
only 57% of the dose was eliminated from the body.

From the data of Dorman et al. (1994) and Medinsky et al. (1997),
it can further be calculated that 48 h following the start of a 2-h
inhalation exposure to 900 ppm of 14C-methanol vapors
in female cynomolgus monkeys,
only 23% of the absorbed 14C-methanol was eliminated from the body.

These findings are corroborated by the data of Heck et al. (1983)
showing that 40% of a 14C-formaldehyde inhalation dose remained
in the body 70 h postexposure.

In the present study, the model proposed rests on acute exposure data,
where the time profiles of methanol and its metabolites were determined
only over short time periods
(a maximum of 6 h of exposure and a maximum of 48 h postexposure).

This does not allow observation of the slow release from the long-term
components.

It is to be noted that most of the published studies on the detailed
disposition kinetics of methanol regard controlled short-term
(iv injection or continuous inhalation exposure over a few hours)
methanol exposures in rats, primates, and humans
(Batterman et al., 1998; Damian and Raabe, 1996;
Dorman et al., 1994; Ferry et al., 1980; Fisher et al., 2000;
Franzblau et al., 1995; Horton et al., 1992; Jacobsen et al., 1988;
Osterloh et al., 1996; Pollack et al., 1993; Sedivec et al., 1981;
Ward et al., 1995; Ward and Pollack, 1996).

Experimental studies on the detailed time profiles following controlled
repeated exposures to methanol are lacking."

"Thus, in monkeys and plausibly humans, a much larger fraction of body
formaldehyde is rapidly converted to unobserved forms
rather than passed on to formate and eventually CO2."

"However, the volume of distribution of formate was larger than that of
methanol, which strongly suggests that formate distributes in body
constituents other than water, such as proteins.

The closeness of our simulations to the available experimental data
on the time course of formate blood concentrations is consistent
with the volume of distribution concept (i.e., rapid exchanges between
the nonblood pool of formate and blood formate)."

"Also, background concentrations of formate are subject to wide
interindividual variations
(Baumann and Angerer, 1979; D'Alessandro et al., 1994;
Franzblau et al., 1995; Heinrich and Angerer, 1982; Lee et al., 1992;
Osterloh et al., 1996; Sedivec et al., 1981)."

http://www.toxsci.oupjournals.org/cgi/content/full/64/2/169

Toxicological Sciences 64, 169-184 (2001)
Copyright © 2001 by the Society of Toxicology

BIOTRANSFORMATION AND TOXICOKINETIC

A Biologically Based Dynamic Model for Predicting the Disposition of
Methanol and Its Metabolites in Animals and Humans

Michèle Bouchard *, #,1, bouchmic@magellan.umontreal.ca

Robert C. Brunet, # brunet@dms.umontreal.ca

Pierre-Olivier Droz, #

and Gaétan Carrier* gaetan.carrier@umontreal.ca

* Department of Environmental and Occupational Health,
Faculty of Medicine, Université de Montréal, P.O. Box 6128,
Main Station, Montréal, Québec, Canada, H3C 3J7;

# Institut Universitaire romand de Santé au Travail,
rue du Bugnon 19, CH-1005, Lausanne, Switzerland, and

# Département de Mathématiques et de Statistique and Centre de
Recherches Mathématiques, Faculté des arts et des sciences,
Université de Montréal, P.O. Box 6128, Main Station, Montréal,
Québec, Canada, H3C 3J7

NOTES

1 To whom correspondence should be addressed at Département
de santé environnementale et santé au travail, Université de Montréal,
P.O. Box 6128, Main Station, Montréal, Québec, H3C 3J7, Canada.
Fax: (514) 343-2200. E-mail: bouchmic@magellan.umontreal.ca
******************************************************

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

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

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

Using proton transfer reaction-mass spectrometry
for trace gas analysis of the human breath,
the concentrations of methanol and ethanol have been
measured for various test persons consuming alcoholic beverages
and various amounts of fruits, respectively.
The methanol concentrations increased from a natural (physiological)
level of approximately 0.4 ppm up to approximately 2 ppm
a few hours after eating about 1/2 kg of fruits,
and about the same concentration was reached
after drinking of 100 ml brandy
containing 24% volume of ethanol and 0.19% volume of methanol.
PMID: 8561283
[ For the 100 mg brandy, 24 ml means 19 g ethanol,
and 0.19 ml means 0.15 g = 150 mg methanol.
One L diet soda has 61.5 mg methanol in the aspartame molecule,
so 100 ml diet soda has 6.15 mg methanol,
while the 100 ml brandy has 24.4 times more methanol. ]

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte [red blood cell]
membrane enzyme activity, KH Schulpis et al, two studies in 2005,
Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
Murray 2006.01.14

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[ The lowest dose level tested, 34 mg aspartame per kg body weight,
well below the FDA daily human limit of 50 mg/kg, 16 12-oz cans,
caused enzyme activity reduction by -33% in human red blood cell
membranes. ]

However, a missed opportunity in both studies is that the inevitable,
extremely and cumulatively toxic products of methanol in the human
body, formaldehyde and formic acid, which are responsible for the
toxicity of methanol, were not independently tested.

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

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

Stylianos Tsakiris. stsakir@cc.uoa.gr;

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

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

[ Papoutsakis T. tina.papoutsakis@hua.gr;

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

Abstract:

Studies have implicated aspartame (ASP) with neurological problems.
The aim of this study was to evaluate acetylcholinesterase (AChE)
activity in human erythrocyte [red blood cell] membranes
after incubation with the sum of ASP metabolites,
phenylalanine (Phe),
methanol (met) and
aspartic acid (aspt),
or with each one separately.

Erythrocyte [human red blood cell] membranes were obtained from
12 healthy individuals and were incubated with ASP hydrolysis
products for 1h at 37 degrees C.
AChE was measured spectrophotometrically.

Incubation of membranes with ASP metabolites corresponding
with 34 mg/kg, 150 mg/kg or 200 mg/kg of ASP consumption
resulted in an enzyme activity reduction by -33%, -41%, and -57%,
respectively.

Met concentrations 0.14 mM, 0.60 mM, and 0.80 mM decreased
the enzyme activity by -20%, -32% or -40%, respectively.

Aspt concentrations 2.80 mM, 7.60 mM or 10.0 mM inhibited
membrane AChE acitivity by -20%, -35%, and -47%, respectively.

Phe concentrations 0.14 mM, 0.35 mM or 0.50 mM reduced the
enzyme activity by -11%, -33%, and -35%, respectively.

Aspt or Phe concentrations 0.82 mM or 0.07 mM, respectively,
did not alter the membrane AChE activity.

It is concluded that low concentrations of ASP metabolites had
no effect on the membrane enzyme activity,
whereas high or toxic concentrations partially or remarkably
decreased the membrane AChE activity, respectively.
Additionally, neurological symptoms, including learning and memory
processes, may be related to the high or toxic concentrations of the
sweetener metabolites. PMID: 16129618

http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 2003.01.05 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@atlas.uoa.gr;
K.H. Schulpis inchildh@otenet.gr; G.J. Reclos reklos@otenet.gr;

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

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

http://groups.yahoo.com/group/aspartameNM/message/1286
methanol products (formaldehyde and formic acid) are main cause of
alcohol hangover symptoms [same as from similar amounts of
methanol, the 11% part of aspartame]: YS Woo et al, 2005 Dec:
Murray 2006.01.20

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

[ Han-Kyu Lee ]

A hangover is characterized by the unpleasant physical and mental
symptoms that occur between 8 and 16 hours after drinking alcohol.
After inducing experimental hangover in normal individuals,
we measured the methanol concentration prior to
and after alcohol consumption
and we assessed the association between the hangover condition
and the blood methanol level.
A total of 18 normal adult males participated in this study.
They did not have any previous histories of psychiatric
or medical disorders.
The blood ethanol concentration prior to the alcohol intake
(2.26+/-2.08) was not significantly different from that
13 hours after the alcohol consumption (3.12+/-2.38).
However, the difference of methanol concentration
between the day of experiment (prior to the alcohol intake)
and the next day (13 hours after the alcohol intake)
was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively).
A significant positive correlation was observed
between the changes of blood methanol concentration
and hangover subjective scale score increment when covarying
for the changes of blood ethanol level (r=0.498, p<0.05).
This result suggests the possible correlation of methanol
as well as its toxic metabolite to hangover. PMID: 16318957
[ The toxic metabolite of methanol is formaldehyde, which in turn
partially becomes formic acid -- both potent cumulative toxins
that are the actual cause of the toxicity of methanol.]
*******************************************************

Alcohol. 2003 Nov;31(3): 167-70.
Effects of alcohol hangover on cytokine production in healthy subjects.
Kim DJ, Kim W, Yoon SJ, Choi BM, Kim JS, Go HJ,
Kim YK, Jeong J.
Department of Psychiatry, College of Medicine,
The Catholic University of Korea, 137-701 Seoul, South Korea.
KDJ922@chollian.net

A hangover is the syndrome of physical and mental symptoms that
occurs 8 to 16 h after alcohol consumption with a zero level of alcohol.
The aim of the current study was to investigate the effects of the alcohol
hangover on cytokine production in healthy subjects.
The hangover state was defined as 13 h after drinking 1.5 g/kg
of alcohol (blood alcohol level=0).
A venous blood sample was taken from 20 healthy adult men
before consumption of alcohol and during the hangover state.
Peripheral blood mononuclear cells were separated
and stimulated with phytohemagglutinin.
An enzyme-linked immunosorbent assay was used to measure
the production of the following cytokines:
interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-12,
interferon-gamma (IFN-gamma),
and tumor necrosis factor-alpha (TNF-alpha).
We found that the concentrations of IL-10, IL-12, and IFN-gamma
were significantly increased during the hangover state compared with the
concentrations in normal conditions.
These results support the suggestion that
the dysregulated cytokine pathway (IL-10, IL-12, and IFN-gamma)
is associated with the symptoms of hangovers. PMID: 14693266

Int J Neurosci. 2003 Apr; 113(4): 581-94.
The effects of alcohol hangover on cognitive functions in healthy subjects.
Kim DJ, Yoon SJ, Lee HP, Choi BM, Go HJ.
Department of Psychiatry, College of Medicine,
Catholic University of Korea, Buchon City, Kyunggi Do, Korea.

A hangover is characterized by the constellation of unpleasant physical
and mental symptoms that occur between 8 and 16 h
after drinking alcohol.
We evaluated the effects of experimentally-induced alcohol hangover on
cognitive functions using the Luria-Nebraska Neuropsychological Battery.
A total of 13 normal adult males participated in this study.
They did not have any previous histories
of psychiatric or medical disorders.
We defined the experimentally-induced hangover condition at 13 h
after drinking a high dose of alcohol (1.5 g/kg of body weight).
We evaluated the changes of cognitive functions before drinking alcohol
and during experimentally-induced hangover state.
The Luria-Nebraska Neuropsychological Battery was administrated
in order to examine the changes of cognitive functions.
Cognitive functions, such as visual, memory,
and intellectual process functions,
were decreased during the hangover state.
Among summary scales, the profile elevation scale was also increased.
Among localization scales, the scores of left frontal, sensorimotor,
parietal-occipital dysfunction, and right parietal-occipital scales
were increased during the hangover state.
These results indicate that alcohol hangovers have a negative effect
on cognitive functions, particularly on the higher cortical and
visual functions associated with the left hemisphere
and right posterior hemisphere.
Publication Types: Clinical Trial PMID: 12856484

Drug Alcohol Depend. 2006 Jan 4; 81(1): 83-8. Epub 2005 Jul 6.
Increased white matter hyperintensities
in male methamphetamine abusers.
Bae SC, Lyoo IK, Sung YH, Yoo J, Chung A, Yoon SJ,
Kim DJ, Hwang J, Kim SJ, Renshaw PF.
Department of Psychiatry, Seoul National University College
of Medicine and Hospital, 28 Yongon-dong, Chongno-gu,
Seoul 110-744, South Korea;
Interdisciplinary Program for Neuroscience,
Seoul National University, Seoul, South Korea.

BACKGROUND:
The current study was conducted to compare the prevalence,
severity, and location of white matter signal hyperintensities (WMH)
on brain magnetic resonance (MR) imaging
in methamphetamine (MA) abusers.
METHODS:
Thirty-three MA abusers and 32 age- and gender-matched healthy
comparison subjects were studied.
Axial T-2 weighted images and fluid attenuated inversion recovery
axial images were obtained using 3.0T MR scanner.
The severity of WMH was assessed separately for deep and
periventricular WMH.
Ordinal logistic regression models were used to assess
the odds ratio for WMH.
RESULTS:
MA abusers had greater severity of WMH than the healthy comparison
subjects (odds ratio: 7.06, 8.46, and 4.56
for all, deep, and periventricular WMH, respectively).
Severity of deep WMH correlated with total cumulative dose
of MA (p=0.027).
Male MA abusers had greater severity of WMH
than female MA abusers (odds ratio=10.00).
While male MA abusers had greater severity of WMH
than male comparison subjects (odds ratio=18.86),
there was no significant difference in WMH severity
between female MA abusers and female comparison subjects.
CONCLUSIONS:
The current study reports increased WMH in MA abusers,
which may be related to MA-induced cerebral perfusion deficits.
In addition, female MA abusers had less severe WMH
than male MA abusers,
possibly due to estrogen's protective effect against ischemic
or neurotoxic effects of MA. PMID: 16005161

Exp Mol Med. 2005 Dec 31; 37(6): 533-45.
Role of gamma-aminobutyricacidB(GABA(B)) receptors in the regulation
of kainic acid-induced cell death in mouse hippocampus.
Lee HK, Seo YJ, Choi SS, Kwon MS, Shim EJ, Lee JY, Suh HW.
Department of Pharmacology and Institute of Natural Medicine,
College of Medicine, Hallym University, Chuncheon 200-702, Korea.

Kainic acid (KA) is well-known as an excitatory, neurotoxic substance.
In mice, KA administered intracerebroventricularly (i.c.v.)
lead to morphological damage of hippocampus
expecially concentrated on the CA3 pyramidal neurons.
In the present study, the possible role of gamma-aminobutyric acid B
(GABA(B)) receptors in hippocampal cell death
induced by KA (0.1 microg) administered i.c.v. was examined.
5-Aminovaleric acid (5-AV; GABA(B) receptors antagonist, 20 mug)
reduced KA-induced CA3 pyramidal cell death.
KA increased the phosphorylated extracellular signal-regulated
kinase (p-ERK) and
Ca(2+)/calmodulin-dependent protein kinase II (p-CaMK II)
immunoreactivities (IRs) 30 min after KA treatment,
and c-Fos, c-Jun IR 2 h, and glial fibrillary acidic protein (GFAP),
complement receptor type 3 (OX-42) IR 1 day in hippocampal area
in KA-injected mice.
5-AV attenuated KA induced
p-CaMK II, GFAP and OX-42 IR in the hippocampal CA3 region.
These results suggest that p-CaMK II may play as an important regulator
on hippocampal cell death induced by KA administered i.c.v. in mice.
Activated astrocytes, which was presented by GFAP IR,
and activated microglia,
which was presented by the OX-42 IR,
may be a good indicator for measuring the cell death in hippocampal
regions by KA excitotoxicity.
Furthermore, it showed that GABA(B) receptors appear to be involved
in hippocampal CA3 pyramidal cell death induced
by KA administered i.c.v. in mice. PMID: 16391514

Neurosci Res. 2005 Dec; 53(4): 391-5. Epub 2005 Oct 3.
Ghrelin precursor gene polymorphism and methamphetamine dependence
in the Korean population.
Yoon SJ, Pae CU, Lee H, Choi B, Kim TS, Lyoo IK,
Kwon DH, Kim DJ.
Department of Psychiatry, St. Paul's Hospital, College of Medicine,
The Catholic University of Korea, Republic of Korea.

Ghrelin is a recently isolated brain-gut peptide that has growth
hormone-releasing and appetite-inducing activities.
Several recent studies have suggested that ghrelin plays a major role
in the pathophysiology of drug-seeking behavior and anxiety.
Therefore, we assessed the effect of the ghrelin precursor polymorphism
on methamphetamine dependence in the Korean population.
One hundred and eighteen patients
with methamphetamine dependence, according to the Diagnostic
and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria,
and the 144 healthy controls were enrolled in this study.
Genotyping for the ghrelin precursor polymorphism was performed by
the polymerase chain reaction-restriction
fragment length polymorphism-based technique.
The genotypic and allelic distributions of the ghrelin precursor
polymorphism in the patients with methamphetamine dependence
were not significantly different from those of the control subjects.
However, the Met72 carriers were associated with
the emotional problems of methamphetamine dependence.
The patients with the Met72 allele were more depressed
and anxious than the homozygous patients with the wild Leu72 allele.
The present study suggests that the ghrelin precursor polymorphism may
not confer a susceptibility to the development of methamphetamine
dependence in the Korean population.
However, the Leu72Met polymorphism could have a potential role
in the emotional problems that are associated with this disease.
PMID: 16207498

Neurosci Lett. 2005 Nov 11; 388(2): 112-5.
High concentrations of plasma brain-derived neurotrophic factor in
methamphetamine users.
Kim DJ, Roh S, Kim Y, Yoon SJ, Lee HK, Han CS, Kim YK.
Department of Psychiatry, College of Medicine,
Korea University Ansan Hospital, Kyunggi Province, Seoul, Korea.

Methamphetamine is a highly addictive drug that has a neurotoxic effect
on the brain.
A growing body of evidence suggests that brain-derived neurotrophic factor
(BDNF) is associated with addictive behavior.
The present study investigated the changes in plasma BDNF concentration
that were induced by chronic methamphetamine use.
Using an enzyme-linked immunosorbent assay (ELISA), we measured
peripheral BDNF levels in methamphetamine users
and in a control group.
The plasma BDNF concentrations of methamphetamine users
were significantly higher compared with those of controls
(2536.3 pg/ml versus 1352.6 pg/ml).
This finding suggests that BDNF plays some role
in the neurotoxicity of methamphetamine. PMID: 16039058

J Prev Med Pub Health. 2005 May; 38(2): 175-81.
[Estimating the burden of diseases due to high alcohol consumption
in Korea]
[Article in Korean]
Lee JK, Kim YI, Yoon SJ, Lee JY, Lee H, Park JH, Shin Y.
Ministry of Health and Welfare,
Department of Health Policy and Management,
Seoul National University College of Medicine. jungkyu@mohw.go.kr

OBJECTIVES:
This study estimated the burden of disease due to high alcohol
consumption using DALY,
a composite indicator recently developed
by the Global Burden of Disease study group.
The results were analyzed by age and sex.
METHODS:
Firstly, high alcohol consumption-related diseases,
and their relative risk (RR), were selected.
Secondly, population attributable fractions (PAFs) were computed
using formulae,
including the relative risk (RR) and prevalence of exposure (Pe).
Thirdly, the DALYs of high alcohol consumption-related diseases
were estimated.
Lastly, the attributable burdens of diseases due to high alcohol consumption
were concluded as being the sum
of the products that multiplied the DALYs
of high alcohol consumption-related diseases
by their population attributable fraction (PAF).
RESULTS:
The burden of high alcohol consumption in Korea was
2992.3 person years (PYs) per 100,000 persons in men,
and 1426.6 in women.
For men, the high alcohol consumption-induced diseases
with the five biggest burdens were
liver cirrhosis, hypertensive disease, liver cancer, cerebral infarction and
intracerebral hemorrhage.
For women, these were cerebral infarction, intracerebral hemorrhage,
hypertensive disease, liver cirrhosis and liver cancer.
CONCLUSION:
This study highlighted the attributable fraction of diseases due to exposure
to high alcohol consumption,
by quantifying the results of exposure to risk factors.
Therefore, it is now possible to assess interventions for risk factors
in quantifiable terms in each population.
Finally, measuring the risk factor burdens was expected to contribute
to priority setting and effective resource allocation in public health
policy.
PMID: 16315755

Alcohol Alcohol. 2005 Jan-Feb; 40(1): 76-79.
Epub 2004 Nov 1.
Increased fasting plasma ghrelin levels during alcohol abstinence.
Kim DJ, Yoon SJ, Choi B, Kim TS, Woo YS, Kim W, Myrick H,
Peterson BS, Choi YB, Kim YK, Jeong J.
Department of Psychiatry, KARF Hospital, 1241 Backseokdong,
Ilsangu, Goyangsi, Gyeonggido 411-816, South Korea.

AIMS:
Ghrelin is a peptide hormone that antagonizes the action of leptin and is
thereby thought to regulate feeding behaviour.
The actions of ghrelin and leptin appear to be mediated by the
neuropeptide Y (NPY) and Agouti-related protein (AGRP) system.
Recent studies have suggested that leptin and NPY
play significant roles in the pathophysiology of alcoholism.
The aim of this study was to determine
whether ghrelin is associated with the state and duration
of abstinence in individuals with alcohol dependence.
METHODS:
Fasting plasma ghrelin levels were compared between 47 individuals
with chronic alcoholism during a period of abstinence
and 50 control subjects.
RESULTS:
Fasting plasma ghrelin levels were higher in alcohol abstainers
than those in controls.
Furthermore, a positive correlation was observed between ghrelin levels
and the duration of abstinence.
In addition, daily alcohol intake prior to abstinence
was inversely related to ghrelin levels.
CONCLUSIONS:
These findings suggest that ghrelin plays a role
in the pathogenesis of alcohol dependence,
particularly during the abstinence period,
in individuals with chronic alcoholism. PMID: 15520048
*******************************************************