Posted: 23 February 2010
Chemico-Biological Interactions, JA Bond, MA Medinsky, can share WC Monte paradigm re harm by formaldehyde via ADH enzyme & methanol in blood capillaries -- tobacco, wood smoke; dark wines, liquors; aspartame; canned tomatoes: Rich Murray 2011.02.21
Monday, February 21, 2011
[at end of each long page, click on Older Posts]
This would meet an urgent need to inform, heal, and protect people worldwide.
http://whilesciencesleeps.com/about WC Monte paradigm
http://ees.elsevier.com/chembioint CBI private journal, Santa Fe, NM
Remember, the dose makes the poison The New Mexican
Posted: Saturday, February 19, 2011 [Standard aspartame PR...]
[More info from these sources is given at the end of this post.]
Cynde Reid Gustafson wrote:
From: "Cynde Reid Gustafson" firstname.lastname@example.org
Subject: Chemico-Biological Interactions
Date: Mon, 5 Nov 2001 19:43:12 –0500
Content available at: http://www.sciencedirect.com/science/journal/00092797
Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes.
Special emphasis is placed on mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro.
Endpoints of interest include, but are not limited to, carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.
Subscribers have access to full-text articles.
Editor: James A. Bond, Ph.D.
Remember, the dose makes the poison The New Mexican
Posted: Saturday, February 19, 2011 - 2/20/11
In 1933, at his first inauguration, President Franklin D. Roosevelt famously stated, "The only thing we have to fear is fear itself." Although this statement was made in response to a bank panic in the midst of the Great Depression, the same sentiment can describe what is an overreaction to the common artificial sweetener, aspartame, which was relayed in the Feb. 13 My View, "Gov. Martínez, take a stand for consumer protection," by Stephen Fox.
Mr. Fox suggests that Gov. Martinez "might take further protective actions about the terrible effects of aspartame." We could not disagree more with this recommendation because it strikes fear in the minds of people regarding the use of aspartame in consumer products including soft drinks, Jell-O and gum. As board-certified toxicologists, we consider the statements in the article regarding aspartame toxicity such as, "aspartame ... a poisonous substance," "terrible effects of aspartame" and "neurotoxic, carcinogenic artificial sweetener" misleading and without scientific basis.
We have no financial or other interest in aspartame. Our interest derives from the desire to advise others against making statements regarding the toxicity of materials, including aspartame, without using sound scientific and toxicological principles.
The fundamental principle in the science of toxicology is "the dose makes the poison." This principle was articulated by Paracelsus, a 15th-century physician, who stated "What is there that is not poison?" What we find lacking in Mr. Fox's view is a discussion regarding dose. Instead, there is the implicit assumption that any intake of aspartame, however small, will have adverse health effects, including cancer and neurological disorders. Nothing could be further from the truth.
Aspartame is composed of two common amino acids, aspartic acid and phenylalanine. Amino acids are the building blocks for proteins. After ingestion, aspartame is broken down into these two amino acids with the release of methanol.
Methanol is further transformed by the body into formaldehyde and formate. The amount of methanol (and thus formaldehyde and formate) produced by the breakdown of aspartame is less than what is in fruit or fruit juices, where methanol occurs naturally.
It is true that at high doses methanol can cause blindness or even death, but the levels of methanol that are produced after consuming aspartame are hundreds of times lower than the doses of methanol that cause toxicity.
High doses, poisonous; low doses, not poisonous.
Numerous regulatory agencies, including the FDA, have reviewed the toxicological data on aspartame collected in laboratory animals and people and have concluded that aspartame is not carcinogenic and is safe at the Accepted Daily Intake level.
This is the amount of a substance that can be consumed every day over a lifetime without any adverse effects.
The ADI for aspartame is 50 milligrams/kilogram of body weight, or the equivalent of drinking 21 cans of diet soda daily for an average adult.
The FDA also reviewed reports suggesting that aspartame is neurotoxic and found them to be without merit. We say to Gov. Martínez, yes, take a stand for consumer protection, but focus on facts, not fear.
James A. Bond, Ph.D., and Michele A. Medinsky, Ph.D. are toxicology consultants in Santa Fe.
Aspartame in Merck Maxalt-MLT worsens migraine, AstraZeneca Zomig, Eli Lilly Zyprexa, J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab, Pfizer Cool Mint Listerine Pocketpaks: Murray 2002.07.16
Migraine MLT-Down: an unusual presentation of migraine in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame, giving 0.4 mg methanol, while 12 oz diet soda has 200 mg, methanol 22 mg.]
Headache Institute, St. Lukes-Roosevelt Hospital Center
New York, NY
Department of Neurology email@example.com
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research RLipton@aecom.yu.edu
Blumenthall & Vance: aspartame chewing gum headaches
Nov 1997: Murray 2002.07.28
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches. Headache 1997 Nov; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine, Tulsa, USA. firstname.lastname@example.org
Aspartame, a popular dietetic sweetener, may provoke headache in some susceptible individuals. Herein, we describe three cases of young women with migraine who reported their headaches could be provoked by chewing gum sweetened with aspartame.
[6-8 mg aspartame per stick chewing gum]
Older women drinking over 2 aspartame beverages weekly had 30% decline kidney function in 11 years, Nurses Health Study, Julie Lin, Gary C Curhan, Brigham and Women's Hospital, Boston: Rich Murray 2009.11.02
Monday, November 2, 2009
[Over 400 mg aspartame/7 days = over 57 mg aspartame/day, over 6 mg methanol/day ]
"Lin's team looked at the cumulative average beverage intake, derived from food questionnaires completed in 1984, 1986, and 1990. The women replied whether they drank the beverages less than once a month, one to four times a month, two to six times weekly, once daily but less than twice, or twice a day or more often."
[Aspartame, approved in the USA for beverages in July, 1983, was by far the dominant artificial sweetener in beverages in 1984 to 1990.]
3,267 women, median age 67 in 2000, in Nurses Health Study:
"When the researchers compared kidney function of the women in 1989 and 2000, they found that 11.4% or 372 women had a kidney function decline of 30% or more. When they looked at the diet information, they found that the 30% decline in kidney function was associated with drinking two or more artificially sweetened sodas a day. This was true even after taking into account factors such as age, high blood pressure, diabetes, and physical activity."... [more]
James A. Bond, Ph.D., DABT
25 Rabbitbrush Road, Santa Fe, NM 87506-7782, USA
Fax: +1 505 988 1298, Tel: +1 505 988 1298
[M. Medinski has the same phone number]
Department of Molecular Toxicology, School of Pharmacy, University of Southern California (USC), 1985 Zonal Avenue- PSC 616, Los Angeles, 95616-8501, USA, Fax: +1 323 224 7473, Tel: +1 323 442 1418, Email: email@example.com
Department of Pediatrics, TBRC/CRI/CPPT, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA, Fax: +1 414 955 6651, Tel: +1 414 456 4322, Email: firstname.lastname@example.org
Albert P. Li, Ph.D.
In Vitro ADMET Laboratories LLC, Advanced Pharmaceutical Sciences, Inc., 15235 Shady Grove Road, Suite 303, Rockville, 20850, USA, Fax: +1 301 926 8891, Tel: + 1 301 926 4900, Email: email@example.com
Inst. of Environmental Medicine, Division of Biochemical Toxicology, Karolinska Institutet, Box 210, S-171 77 Stockholm, Sweden, Fax: +46 8 343849, Tel: +46 8 524 87574, Email: Ralf.Morgenstern@ki.se
Abby C. Collier
Assistant Professor of Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, BioSciences 320-3, 651 Ilalo Street, Honolulu, HI 96813, USA, Fax: +1 808 692 1777, Tel: +1 808 692 1613, Email: firstname.lastname@example.org
Antiseptic? antifungal? antiviral? methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full plain text, 2001: substantial sources are degradation of fruit pectins, liquors, aspartame, smoke: Murray 2005.01.05 rmforall
Free full text
A Biologically Based Dynamic Model for Predicting the Disposition of Methanol and Its Metabolites in Animals and Humans.
Robert C. Brunet,
and Gaétan Carrier.
Toxicological Sciences 64, 169-184 (2001)
Copyright © 2001 by the Society of Toxicology
"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).
[It's unusual for a mainstream journal article to mention "fruits, fruit juices, certain vegetables, aspartame sweetener" and "alcoholic beverages" to be methanol sources.]
... little is known about the chronic effects of low exposure doses... Systemic methanol is extensively metabolized by liver alcohol dehydrogenase [ ADH ] and catalase-peroxidase enzymes to formaldehyde, which is in turn rapidly oxidized to formic acid by formaldehyde dehydrogenase enzymes...
Formaldehyde, as it is highly reactive, forms relatively stable adducts with cellular constituents...
Primates and humans appear to be more susceptible to the acute toxicity of methanol than rodents...
Although methanol has been reported to be metabolized mainly in the liver, pulmonary metabolism is also likely to occur. Indeed, the catalase-peroxidase system responsible for a major fraction of methanol metabolism in rats is widely distributed in mammalian tissues...
The model included a constant background whole body methanol burden of 2.133 mmol, which corresponds to the mean blood concentration of 0.5 mg/L of methanol measured by Osterloh et al. (1996) in control subjects at the end of an 8-h frequent blood sampling period...
... 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; Roe, 1982)...
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...
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."
If we assume 30% retention of durable cumulative toxic products of formaldehyde and formic acid, then a 12-oz can diet drink gives 200 mg aspartame, 22 mg methanol, and 7 mg formaldehyde and formic acid at 30% cumulative retention. We may add that well-known sources of formaldehyde include both wood and tobacco smoke, and, notoriously, mobile homes. Two teams give evidence that formaldehyde and formic acid from methanol in ethanol drinks (often far above the 100 mg/L methanol in red wines, two times the level in aspartame drinks) are the main cause of the many symptoms of "morning after" hangovers.
Folic acid prevents neurotoxicity from formic acid, made by body from methanol impurity in alcohol drinks [also 11 % of aspartame]
BM Kapur, PL Carlen, DC Lehotay, AC Vandenbroucke, Y Adamchik, U. of Toronto, 2007 Dec., Alcoholism Cl. Exp. Res.: Murray 2007.11.27
Furthermore, BM Kapur et al, 2007 give evidence that formic acid from methanol in ethanol drinks is a major cause of Fetal Alcohol Syndrome, readily preventable by adequate levels of folic acid, which expedites the safe metabolism of formaldehyde, in most people.
"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." ...
"MeOH concentrations between 4 and 4500 mg/l can be present in various alcoholic beverages (Sprung et al., 1988)."
A variety of mutations, as well as aspirin and many painkillers, impede folic acid. However, fruits and vegetables give enough folic acid to mitigate harm from their methanol. Then again, formaldehyde may in many people treat infections by fungi, bacteria, and virusus. All these unexamined co-factors have confused attempts to study aspartame toxicity for three decades.
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.
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 2007.11.27
A widely proclaimed NIH-AARP mass survey by U Lim et al. 2006, while failing to show specific cancers with feeble diet drink consumption data for a year for seniors, did find that 4% of a half-million seniors drank 3 and more cans daily diet soda
[12-oz can gives 200 mg aspartame, 22 mg methanol, 7 mg formaldehyde and formic acid at 30% cumulative retention]
Aspartame mg/d --- 0 ----- under 100 - 100-200 - 200-400 - 400-600 - 600-1200 - over 1200
Cohort % -------- 46 --------- 25 -------- 13 -------- 7 --------- 5 ------ about 3 ----under 1%
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 12oz 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.
The highest level 3400 mg aspartame [ 17 12-oz cans ] gives 11% = 374 mg methanol, 48 times the recommended daily limit of consumption of 7.8 mg as recommended by the Environmental Protection Agency (EPA).3
At 30% retention of cumulative toxic products of formaldehyde and formic acid, these would be 125 mg, 60 times higher than the 1999 EPA alarm level for formaldehyde in daily drinking water of 1 ppm = 2 mg for average daily drinking water of 2 L daily.
Since no adequate 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.
Highly toxic formaldehyde, the cause of alcohol hangovers, is made by the body from 100 mg doses of methanol fromdark wines and liquors, dimethyl dicarbonate, and aspartame: Murray 2007.08.31
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L ( becomes formaldehyde in body ): EU Scientific Committee on Foods 2001.07.12: Murray 2004.01.22
"...DMDC was evaluated by the SCF in 1990 and considered acceptable for the cold sterilization of soft drinks and fruit juices at levels of addition up to 250 mg/L (1) ...DMDC decomposes primarily to CO2 and methanol ...
[Note: Sterilization of bacteria and fungi is a toxic process, probably due to the inevitable conversion in the body of methanol into highly toxic formaldehyde and then formic acid.]
The use of 200 mg DMDC per liter would add 98 mg/L of methanol to wine which already contains an average of about 40 mg/L from natural sources.
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.
Songsin Campus: 02-740-9714
Songsim Campus: 02-2164-4116
Songeui Campus: 02-2164-4114
http://www.cuk.ac.kr/eng/sub055.htm Eight hospitals [Han-Kyu Lee]
A hangover is characterized by the unpleasant physical and mental symptoms that occur between 8 and 16 hours after drinking alcohol.
After inducing experimental hangover in normal individuals, we measured the methanol concentration prior to and after alcohol consumption and we assessed the association between the hangover condition and the blood methanol level.
A total of 18 normal adult males participated in this study.
They did not have any previous histories of psychiatric or medical disorders.
The blood ethanol concentration prior to the alcohol intake (2.26+/-2.08) was not significantly different from that 13 hours after the alcohol consumption (3.12+/-2.38).
However, the difference of methanol concentration between the day of experiment (prior to the alcohol intake) and the next day (13 hours after the alcohol intake) was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively).
A significant positive correlation was observed between the changes of blood methanol concentration and hangover subjective scale score increment when covarying for the changes of blood ethanol level (r=0.498, p<0.05).
This result suggests the possible correlation of methanol as well as its toxic metabolite to hangover. PMID: 16318957
[The toxic metabolite of methanol is formaldehyde, which in turn partially becomes formic acid -- both potent cumulative toxins that are the actual cause of the toxicity of methanol.]
This study by Jones AW (1987) found next-morning hangover from red wine with 100 to 150 mg methanol (9.5 % w/v ethanol, 100 mg/l methanol, 0.01 %). Fully 11% of aspartame is methanol -- 1,120 mg aspartame in 2 L diet soda, almost six 12-oz cans, gives 123 mg methanol (wood alcohol).
Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.
Elimination half-life of methanol during hangover.
Jones AW. wayne.jones@RMV.se
Department of Forensic Toxicology
University Hospital, SE-581 85 Linkoping, Sweden.
This paper reports the elimination half-life of methanol in human volunteers.
Experiments were made during the morning after the subjects had consumed 1000-1500 ml red wine (9.5 % w/v ethanol, 100 mg/l methanol) the previous evening. [100 to 150 mg methanol] The washout of methanol from the body coincided with the onset of hangover.
The concentrations of ethanol and methanol in blood were determined indirectly by analysis of end-expired alveolar air. In the morning when blood-ethanol dropped below the Km of liver alcohol dehydrogenase (ADH) of about 100 mg/l (2.2 mM), the disappearance half-life of ethanol was 21, 22, 18 and 15 min. in 4 test subjects respectively.
The corresponding elimination half-lives of methanol were 213, 110, 133 and 142 min. in these same individuals. The experimental design outlined in this paper can be used to obtain useful data on elimination kinetics of methanol in human volunteers without undue ethical limitations. Circumstantial evidence is presented to link methanol or its toxic metabolic products, formaldehyde and formic acid, with the pathogenesis of hangover. PMID: 3588516
Rich Murray, MA
Boston University Graduate School 1967 psychology
BS MIT 1964, history and physics
1943 Otowi Road,
Santa Fe, New Mexico 87505
http://RMForAll.blogspot.com New primary archive
Group with 118 members, 1,618 posts in a public archive
Group with 1226 members, 24,280 posts in a public archive
Participant, Santa Fe Complex http://www.sfcomplex.org