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Connecticut bans artificial sweeteners in schools, Nancy Barnes, New Milford Times: Murray 2006.05.12

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  • Rich Murray
    Connecticut bans artificial sweeteners in schools, Nancy Barnes, New Milford Times: Murray 2006.05.12 http://groups.yahoo.com/group/aspartameNM/message/1341
    Message 1 of 1 , May 12, 2006
      Connecticut bans artificial sweeteners in schools, Nancy Barnes,
      New Milford Times: Murray 2006.05.12
      http://groups.yahoo.com/group/aspartameNM/message/1341

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

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

      http://groups.yahoo.com/group/aspartameNM/messages
      group with 73 members, 1,341 posts in a public, searchable archive
      http://RMForAll.blogspot.com http://AspartameNM.blogspot.com

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

      http://www.zwire.com/site/news.cfm?newsid=16628924&BRD=1655&PAG=461&dept_id=13091&rfi=6

      School food act knocks soda and snacks
      By: Nancy Barnes 05/12/2006

      When students return to the halls of the New Milford public school
      system this fall, healthier foods and beverages will be in place, thanks
      to "An Act Concerning Healthy Food and Beverages in Schools"
      passed by the General Assembly on April 27.

      The new legislation, which takes effect July 1, applies to "any source"
      within school property, including, but not limited to, school stores,
      vending machines, school cafeterias, and any fund-raising activities on
      school premises, whether or not they are sponsored by the school,
      during regular school hours.

      Milk, for instance, may be flavored but contain no artificial sweeteners
      and no more than four grams of sugar per ounce.
      [ 48 grams per 12 oz ]
      Water may be flavored but contain no added sugars, sweeteners,
      artificial sweeteners or caffeine.
      One hundred percent fruit juice, vegetable juice or a combination
      of these juices shall contain no added sugars, sweeteners
      or artificial sweeteners, according to the legislation.

      "The Department of Education was supportive of it," said Susan Fiore,
      nutrition education coordinator in the State Department of Education,
      referring to the legislation.
      "We've been trying to work to help schools promote healthy eating
      as well as physical activity for kids."

      "It's bigger than an obesity issue," she said with reference to the catalyst
      for the legislation, while terming obesity among school children a big
      epidemic. "The bottom line is healthy kids, no matter what their size."

      "Obesity was the driving force behind all this, because it keeps climbing
      and climbing," she acknowledged. "We worry about the health of all kids.
      Many normal-weight kids are not healthy. They are not eating food that
      will keep them healthy in the long run, like fruits and vegetables."

      "We really looked at the concept of promoting less processing and more
      whole, natural foods," she said, with regard to the ban on
      artificial sweeteners.
      "Even if kids are drinking diet soda, they're not drinking milk,
      and they need to drink water."

      The vote for the legislation was close, with the final tally
      in the House 76 to 74, with four state representatives absent,
      and the vote in the Senate 24 to 8, also with four assemblymen absent.

      "I think it had a lot to do with party lines," Ms. Fiore said,
      noting that the bill came from State Sen. Donald E. Williams, Jr.
      (D-Brooklyn), who is president pro tempore of the state Senate.

      "There was opposition from the soda companies and the Teamsters,"
      she said, noting that the union had argued "there'd be nothing for delivery.

      "The soda companies sell juice. They sell water," she said,
      referring to the new markets the statewide legislation
      will open up as it decreases others.

      The legislation also includes incentives for school districts to apply
      nutritional standards to food that does not fall within federally assisted
      programs such as the National School Lunch Program,
      the School Breakfast Program, the School Milk Program
      and the After-School Snack Program,
      for which the New Milford school district,
      like others throughout the state, is presently reimbursed.

      "There are many other foods at schools that are not reimbursable,"
      she said, citing the sale of hot dogs or hamburgers.

      "There are no standards for those foods so now, everything besides
      the meals will have standards," she said, referring to standards the state
      Department of Education had worked out for foods
      within the past two years.

      The second part of the legislation gives school districts the option of
      applying DOE nutritional standards to all food items it sells.
      "If the school chooses to apply those standards to its food,
      it will get additional funding," she said, adding that the funding formula
      is still being calculated.

      Ms. Fiore affirmed that the legislation leaves optional the sale of foods
      that do not meet its nutritional standards in their faculty areas.
      "The school could choose to leave it in a faculty lounge," she said.
      ©New Milford Times 2006
      *******************************************************

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      http://www.team.uconn.edu/teachers.htm
      Connecticut's Team Nutrition Program

      If you have any questions about Team Nutrition please contact:

      Colleen Thompson, MS, RD (860) 486-1787
      cthompso@...

      Ellen Shanley, MBA, RD, CD-N (860) 486-0119
      eshanley@...

      University of Connecticut
      College of Agriculture and Natural Resources
      Department of Nutritional Sciences

      http://www.team.uconn.edu/teachers.htm#vending
      For more information on Connecticut Team Nutrition
      or the Healthy Vending and Snack Sales Pilot,
      contact Susan S. Fiore, MS, RD, Team Nutrition Director,
      at (860) 807-2075 or susan.fiore@...
      *******************************************************

      The Comet assay can quickly show whether aspartame or its body
      products (methanol, formaldehyde, formic acid -- the same as in
      hangovers from dark wines and liquors) are genotoxic:
      Murray 2006.05.09

      http://groups.yahoo.com/group/aspartameNM/message/1337
      Comet assay finds DNA damage from sucralose, cyclamate, saccharin,
      aspartame in mice: Sasaki YF & Tsuda S Aug 2002:
      Murray 2006.05.08

      [ Borderline evidence, in this pilot study of 39 food additives,
      using test groups of 4 mice, for DNA damage from for stomach, colon,
      liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame --
      a very high dose. Methanol is the only component of aspartame that
      can lead to DNA damage. ]

      http://groups.yahoo.com/group/aspartameNM/message/934
      24 recent formaldehyde toxicity [Comet assay] reports:
      Murray 2002.12.31

      http://groups.yahoo.com/group/aspartameNM/message/961
      genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
      sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
      Murray 2003.01.27 [A detailed look at the data] ]

      This study tests 39 common food additives for DNA damage,
      comparing a control group of 4 mice against
      test groups of 4 mice each, killed 3 hr and 24 hr
      after oral ingestion of up to 2000 mg/kg.

      Aspartame has high values for 2000 mg 3 hr for Stomach, Colon, Liver,
      Bladder, Lung -- not statistically significant for just 4 mice.

      However, there are only 21 unique control groups, with widely varying
      values. By using the averages for all 21 control groups to make
      comparison with the groups exposed to the food additives, it is easy
      to see that many additives cause
      about 140% to about 180% to over 300%
      of the averages of all control groups for the 8 organs measured.
      By using more mice, statistical significance may be easily proved for
      most of these easily noticable high values,
      which are not significant for just 4 mice.

      Mutat Res 2002 Aug 26; 519(1-2): 103-19
      The comet assay with 8 mouse organs: results with 39 currently used
      food additives. Yu F. Sasaki
      Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K,
      Iwama K, Taniguchi K, Tsuda S.
      Laboratory of Genotoxicity, Faculty of Chemical and Biological
      Engineering, Hachinohe National College of Technology,
      Tamonoki Uwanotai 16-1, Aomori 039-1192, Japan.
      yfsasaki-c@...; s.tsuda@...;

      We determined the genotoxicity of 39 chemicals currently in use as food
      additives. They fell into six categories-- dyes, color fixatives and
      preservatives, preservatives, antioxidants, fungicides, and sweeteners.

      We tested groups of four male ddY mice once orally with each additive
      at up to 0.5xLD(50) or the limit dose (2000 mg/kg) and performed the
      comet assay on the glandular stomach, colon, liver, kidney,
      urinary bladder, lung, brain, and bone marrow 3 and 24 h after treatment.

      Of all the additives, dyes were the most genotoxic. Amaranth, Allura
      Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal
      induced dose-related DNA damage in the glandular stomach, colon,
      and/or urinary bladder.

      All seven dyes induced DNA damage in the gastrointestinal organs at a
      low dose (10 or 100mg/kg).

      Among them, Amaranth, Allura Red, New Coccine, and Tartrazine
      induced DNA damage in the colon
      at close to the acceptable daily intakes (ADIs).

      Two antioxidants (butylated hydroxyanisole (BHA) and butylated
      hydroxytoluene (BHT)), three fungicides (biphenyl, sodium
      o-phenylphenol, and thiabendazole), and four sweeteners (sodium
      cyclamate, saccharin, sodium saccharin, and sucralose)
      also induced DNA damage in gastrointestinal organs.

      Based on these results, we believe that more extensive assessment of
      food additives in current use is warranted. PMID: 12160896


      Also tested were acesulfame K, aspartame, stevia, and glycyrrhizin --
      which all came out nonsignificant, while, as the abstract mentions,
      sodium cyclamate had 4, saccharin 3, sucralose 3,
      and sodium saccharin 5 significant results.

      Each test condition had just 4 mice, and, according to the text, each
      additive had its own control group of 4 mice. However, there are only
      21 unique sets of control groups, with 8 sets used once, 10 sets used
      twice, 2 sets used 3 times, and 1 set used 4 times, a total of 38 food
      additives listed [Sodium erythorbic acid was left out of Table 2, while
      mentioned in the report 3 times, "...erythorbic acid and its sodium salt
      did not increase DNA damage in any of the organs studied."].

      Aspartame was assigned the control group that had the highest levels of
      Migration of damaged nuclear DNA for Liver and Bladder,
      and the second highest for Brain.

      The same control group was used for the xanthene dye, erythrosinc,
      which had Migration as high as 42.4+-2.17 um [micro-meter],
      measured on 50 nuclei from stomach cells, 3 hours after ingestion.
      So, the high control groups values had no effect on
      the statistical analysis for erythrosinc.

      The available range of the 21 control groups ranged for the Liver from
      1.1 to 3.6 um. For aspartame, the Liver Migration, the average length
      of the "comet" tail of damaged, broken DNA pulled out of 50 Liver cell
      nuclei by an electric field for 15 minutes, was, average of 4 mice:

      control value used 3.59+-0.50 um [1.1 to 3.6 range in 21 controls]
      2000 mg/kg 3 hr 3.26+-0.16 um
      2000 mg/kg 24 hr 0.57+-0.22 um

      The 3 hr aspartame test value was about the same as the control value.
      This may be discordant with the Trocho (1998) findings that rats given
      200 mg/kg oral doses of aspartame for 11 days, about the same total
      dose, had accumulation of formaldehyde adducts, bound to DNA, RNA,
      and proteins, in liver, kidneys, brain, retinas, and other tissues, at about
      the same total dose, spread over 11 days.

      Appying the lowest available control group liver level 1.06+-0.12 um
      would make the aspartame level of 3.26+-0.16 um significant
      [ratio 3.1].

      How significant is a ratio of about 2?
      I found two examples in the data, where P<.05 existed for BHT, Bladder,
      1000 mg/kg, 3 hr:
      10.9+-1.32 vs control 4.77+-0.40 [range 3.6 to 7.1 for 21 controls],
      [ratio 2.3]
      and sodium cyclamate, Stomach, 1000 mg/kg, 3 hr:
      12.2+-1.38 vs control 6.37+-0.57 [range 4.3 to 8.6 for 21 controls]
      [ratio 1.9].

      However, not significant was:
      sodium saccharin, Liver, 2000 mg/kg, 3 hr:
      5.95+-2.42 vs control 1.94+-0.36 [range 1.1 to 3.6 for 21 controls]
      [ratio 3.1], since the +- error was 33% of the test value. So, if the
      data for 4 mice is scattered, then the mean value of the test group has
      to be over 3 times that of the control group to be significant.

      For Liver, 5 of the 21 control groups, with values 1.67, 1.63, 1.29,
      1.06, 1.65 would make some 3 hr aspartame values
      approach or reach significance.

      Ratios about 2 for different tissues with aspartame that would be close
      to significant would exist for many of the 21 control groups:
      Stomach 1 Colon 5 Liver 5 Bladder 11 Lung 5 .

      The aspartame values at 3 hr are compared with
      the mean values for the 21 control groups:

      Somach --- Colon ------ Liver ------ Kidney ------- Bladder --

      DNA Migration at 3 hr from 2000 mg/kg dose
      8.49+-0.48; 9.18+-0.56; 3.26+-0.16; 1.91+-0.26; 10.7+-2.77;

      mean of 21 control groups
      6.31-------- 5.81 ------- 2.15 ------- 2.25 --------- 5.40 -----

      range of values for 21 control groups
      4.3--8.6 ---- 4.0--8.1----1.1--3.6 --- 1.2--2.9 ----- 3.6--7.1-

      ratio = DNA Migration/control mean
      1.4 ---------- 1.6 -------- 1.5 -------- 0.9 ---------- 2.0 ------


      Lung --------Brain ------ Bone [marrow]

      DNA Migration at 3 hr from 2000 mg/kg dose
      4.13+-1.26; 0.37+-0.70; 1.01+-0.59;

      2.61 -------- 1.48 -------- 1.12 ------- mean of 21 control groups

      1.6--4.7 ---- 0.8--2.6 ---- 0.6--1.9 --- range for 21 control groups

      1.6 ---------- 0.3 --------- 0.9 ---- ratio DNA Migration/control mean

      Wouldn't the average of all the 21 control groups be the best control
      values to use? What would then be the appropriate statistical test?
      How many mice would it take to reach significance for the 5 tissues with
      ratios over 1.4: Stomach, Colon, Liver, Bladder, Lung?

      Aspartame at 24 hours had levels too low to reach significance with any
      of the 21 control groups.

      However, people who are heavy users of aspartame for years are bound
      to accumulate toxic metabolites of the three components of aspartame:
      methanol 11%, phenylalanine 50%, aspartic acid 29%, all genotoxic
      [Trocho (1998), Karakis (1998)].

      Comparing the mean control values to the values for the other 7
      sweeteners:
      Best is acesulfame K, with no significant or high values.

      Good is glycyrrhizin (derived from licorice), two 1.4 ratios for Stomach
      and Brain.

      Next is stevia, with one high value [above ratio 1.4],
      9.48+-1.99 for Bladder, 2000 mg 3 hr, ratio 1.8 .

      Aspartame has high values for 2000 mg 3 hr for Stomach, Colon, Liver,
      Bladder, Lung.

      Sucralose has 3 significant values and 13 high values, for Stomach,
      Colon, Kidney, Bladder, Lung, Brain.

      Sodium cyclamate has 4 significant values and 10 high values for
      Stomach, Colon, Liver, Kidney, Bladder, Lung, Brain, Bone.

      Saccharin has 3 highly significant values for Colon, and 13 high values
      for Stomach, Colon, Kidney, Lung, Brain, Bone.

      Sodium saccharin has 5 highly significant values for Stomach and Colon,
      and 14 high values for Stomach, Liver, Kidney, Bladder,
      Lung, Brain, Bone.

      We should keep in mind that toxicity in humans involves many vulnerable
      groups, years of daily use, often evolution of hypersensitivity, and
      complex interactions with a multitude of foods, additives, other toxins,
      foods, and infections.

      Some of the dye data was earlier published in Tsuda (2001):
      Toxicol Sci 2001 May; 61(1): 92-9
      DNA damage induced by red food dyes orally administered to pregnant
      and male mice.
      Tsuda S, Murakami M, Matsusaka N,
      Kano K, Taniguchi K, Sasaki YF.
      Laboratory of Veterinary Public Health, Department of Veterinary
      Medicine, Faculty of Agriculture, Iwate University, Ueda 3-18-8,
      Morioka, Iwate 020-8550, Japan. s.tsuda@...

      We determined the genotoxicity of synthetic red tar dyes currently used
      as food color additives in many countries, including JAPAN: For the
      preliminary assessment, we treated groups of 4 pregnant mice
      (gestational day 11) once orally at the limit dose (2000 mg/kg) of
      amaranth (food red No. 2), allura red (food red No. 40), or acid red
      (food red No. 106), and we sampled brain, lung, liver, kidney, glandular
      stomach, colon, urinary bladder, and embryo 3, 6, and 24 h after
      treatment.

      We used the comet (alkaline single cell gel electrophoresis) assay to
      measure DNA damage. The assay was positive in the colon 3 h after the
      administration of amaranth and allura red and weakly positive in the
      lung 6 h after the administration of amaranth.

      Acid red did not induce DNA damage
      in any sample at any sampling time.

      None of the dyes damaged DNA in other organs or the embryo.

      We then tested male mice with amaranth, allura red, and a related
      color additive, new coccine (food red No. 18).
      The 3 dyes induced DNA
      damage in the colon starting at 10 mg/kg.

      Twenty ml/kg of soaking liquid from commercial red ginger pickles,
      which contained 6.5 mg/10 ml of new coccine, induced DNA
      damage in colon, glandular stomach, and bladder.

      The potencies were compared to those of other rodent carcinogens. The
      rodent hepatocarcinogen p-dimethylaminoazobenzene
      induced colon DNA damage at 1 mg/kg,
      whereas it damaged liver DNA only at 500 mg/kg.

      Although 1 mg/kg of N-nitrosodimethylamine
      induced DNA damage in liver and bladder,
      it did not induce colon DNA damage.
      N-nitrosodiethylamine at 14 mg/kg
      did not induce DNA damage in any organs examined.
      Because the 3 azo additives we examined
      induced colon DNA damage at a very low dose,
      more extensive assessment of azo additives is warranted.
      PMID: 11294979

      http://groups.yahoo.com/group/aspartameNM/message/935
      comet assay finds DNA damage from sucralose, cyclamate, saccharin
      in mice: Sasaki YF & Tsuda S Aug 2002: Murray 2003.01.01

      The Single Cell Gel Assay is able to detect single-strand and
      double-strand DNA breaks in individual eukaryotic cells;
      requires small numbers of cells (<20,000 per sample);
      can detect DNA damage from low levels of toxic or physical insults;
      and is rapid, simple and efficient.
      In this assay, cells are treated with the agent of interest,
      embedded in agarose on a histological slide,
      the cell membranes are lysed,
      and the slides are placed in an electric field.
      If the DNA has single or double-strand breaks,
      it will flow out of the cells and move toward the anode,
      causing the cell and its DNA to resemble a comet.
      The more DNA released from the cell, the greater the DNA damage.
      A computerized imaging system is used to score and measure
      the comets.
      The Comet assay is not FDA approved as a human medical test,
      so it is not covered by insurance.
      It is used in many human research studies.

      http://cometassay.com/ Comet Assay Interest Group

      http://www.ems-us.org/index.asp Environmental Mutagen Society

      http://www.helix3-inc.com/comet-assay.html

      Addendum:
      summarizing the mean +- variation values for the 21 control groups,
      for each tissue, giving the smallest variation and the largest.

      Stomach --- Colon ------ Liver ------ Kidney ----- Bladder ---

      4.90+-0.26; 4.49+-0.19; 1.91+-0.19; 1.81+-0.13; 5.89+-0.24;
      -- 5% -------- 4% ------- 10% -------- 7% --------- 4% -----

      5.55+-1.26; 7.91+-1.95; 1.29+-0.69; 1.73+-0.96; 5.68+-1.30;
      - 23% ------- 25% ------- 53% ------- 56% ------- 23% -----

      Lung ------- Brain ------- Bone [marrow]

      2.44+-0.17; 2.58+-0.40; 1.16+-0.15;
      -- 7% ------- 16% ------- 13% ------

      2.56+-1.04; 1.09+-1.09; 0.75+-0.75;
      - 41% ------ 100% ---- 100% ------

      We have +- mean variation, for the 21 control groups of 4 mice, from 4
      to 100%. What causes this variation, for a specific strain of mice,
      with the same diet, environment, and age? Are there a number of
      genotoxins in the laboratory diet, with the mice exhibiting many genetic
      susceptibilities? Are there genotoxic infections?

      J Toxicol Sci. 2002 Dec; 27 Suppl 1: 1-8.
      [Genotoxicity studies of stevia extract and steviol by the comet assay]
      [Article in Japanese]
      Sekihashi K, Saitoh H, Sasaki Y. yfsasaki-c@...
      Safety Research Institute for Chemical Compounds Co., Ltd.,
      363-24 Shin-ei, Kiyota-ku, Sapporo 004-0839, Japan.

      The genotoxicity of steviol, a metabolite of stevia extract, was evaluated
      for its genotoxic potential using the comet assay.
      In an in vitro study, steviol at 62.5, 125, 250, and 500 micrograms/ml
      did not damage the nuclear DNA of TK6 and WTK1 cells in the
      presence and absence of S9 mix.
      In vivo studies of steviol were conducted
      by two independent organizations.
      Mice were sacrificed 3 and 24 hr after one oral administration of steviol
      at 250, 500, 1000, and 2000 mg/kg.
      DNA damage in multiple mouse organs was measured by the comet
      assay as modified by us.
      After oral treatment, stomach, colon, liver, kidney and testis DNA were
      not demaged.
      The in vivo genotoxicity of stevia extract was also evaluated for its
      genotoxic potential using the comet assay.
      Mice were sacrificed 3 and 24 hr after oral administration of stevia
      extract at 250, 500, 1000, and 2000 mg/kg.
      Stomach, colon and liver DNA were not damaged.
      As all studies showed negative responses, stevia extract and steviol are
      concluded to not have DNA-damaging activity in cultured cells and
      mouse organs. PMID: 12533916
      *******************************************************

      Dark wines and liquors, as well as aspartame, provide
      similar levels of methanol, above 120 mg daily, for
      long-term heavy users, 2 L daily, about 6 cans.

      Within hours, methanol is inevitably largely turned into formaldehyde,
      and thence largely into formic acid -- the major causes of the dreaded
      symptoms of "next morning" hangover.

      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.

      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.

      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).

      http://groups.yahoo.com/group/aspartameNM/message/1100
      research on aspartame (methanol, formaldehyde, formic acid) toxicity:
      Murray 2004.07.19 rmforall


      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@...
      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).

      [ So, the normal methanol level was 2.62 mg per liter,
      and increasing that by 50% = 1.3 mg per liter to 3.88 mg per liter
      caused hangover symptoms. The human body has about
      5.6 liters blood, so adding 1.3 mg per liter gives an estimate
      of 7.3 mg added methanol, as much as 4 oz diet soda.

      Diet soda is about 200 mg aspartame per 12 oz can,
      which is 22 mg (11% methanol), 1.83 mg methnol per ounce.

      This suggests that alcohol drinkers are more sensitive to methanol
      than the average diet soda drinker, some of whom find symptoms
      from a third of a diet soda.]

      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.]
      *******************************************************

      http://groups.yahoo.com/group/aspartameNM/message/1100
      research on aspartame (methanol, formaldehyde, formic acid) toxicity:
      Murray 2004.07.16

      http://groups.yahoo.com/group/aspartameNM/message/1052
      DMDC: Dimethyl dicarbonate 200mg/L in drinks adds
      methanol 98 mg/L [ becomes formaldehyde in body ]: EU Scientific
      Committee on Foods 2001.07.12: Murray 2004.01.22

      http://groups.yahoo.com/group/aspartameNM/message/1143
      methanol [formaldehyde, formic acid] disposition: Bouchard M et al,
      full plain text, 2001: substantial sources are degradation of fruit pectins,
      liquors, aspartame, smoke: Murray 2005.05.30 2005.07.24 rmforall

      "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 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 full text

      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 *, #, michele.bouchard@...

      Robert C. Brunet, # brunet@...

      Pierre-Olivier Droz, #

      and Gaétan Carrier* gaetan.carrier@...

      * Department of Environmental and Occupational Health,
      Faculty of Medicine, Université de Montréal, P.O. Box 6128,
      Main Station, Montréal, Québec, Canada, H3C 3J7
      Fax: (514) 343-2200

      # 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
      *******************************************************


      http://groups.yahoo.com/group/aspartameNM/message/1328
      migraine from sucralose, Bigal ME & Krymchantowski AV,
      Headache 2006 March; formaldehyde from 11% methanol part of
      aspartame or from red wine causes same toxicity (hangover) harm:
      Murray 2006.05.04

      http://groups.yahoo.com/group/aspartameNM/message/1329
      aspartame or MSG affects circadian rhythms in rats, two studies,
      P. Subramanian, T. Manivasagam et al 2004:
      Murray 2006.04.27

      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

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

      http://groups.yahoo.com/group/aspartameNM/message/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@...;
      K.H. Schulpis inchildh@...; G.J. Reclos reklos@...;

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