Loading ...
Sorry, an error occurred while loading the content.

methanol from cigarette and wood smoke, aspartame, canned fruits -- made into formaldehyde by ADH1 enzyme in islets of Langerhans in pancreas -- causes epigenetic changes in diabetes 2 -- WC Monte paradigm: Rich Murray 2014.03.10

Expand Messages
  • Rich Murray
    methanol from cigarette and wood smoke, aspartame, canned fruits -- made into formaldehyde by ADH1 enzyme in islets of Langerhans in pancreas -- causes
    Message 1 of 1 , Mar 10 12:14 AM
    • 0 Attachment
      methanol from cigarette and wood smoke, aspartame, canned fruits -- made into formaldehyde by ADH1 enzyme in islets of Langerhans in pancreas -- causes epigenetic changes in diabetes 2 -- WC Monte paradigm: Rich Murray 2014.03.10



      free full text

      Editor: 
      John M. Greally, Albert Einstein College of Medicine, United States of America

      Received:
      July 20, 2013; Accepted: December 20, 2013; Published: March 6, 2014

      Tasnim Dayeh <Tasnim.Dayeh@...>,
      Petr Volkov,
      Sofia Salö,
      Elin Hall, 
      Emma Nilsson,
      Anders H. Olsson,
      Clare L. Kirkpatrick, 
      Claes B. Wollheim, 
      Lena Eliasson,
      Tina Rönn, 
      Karl Bacos,
      Charlotte Ling <charlotte.ling@...>,

      Genome-Wide DNA Methylation Analysis of Human Pancreatic Islets from Type 2 Diabetic and Non-Diabetic Donors Identifies Candidate Genes That Influence Insulin Secretion. 

      PLoS Genetics, 2014; 10 (3): e1004160
      DOI: 10.1371/journal.pgen.1004160



      Featured Research
      from universities, journals, and other organizations

      Epigenetic changes could explain type 2 diabetes

      Date: March 7, 2014
      Source: Lund University

      Summary:

      People with type 2 diabetes have epigenetic changes on their DNA that healthy individuals do not have. 
      This has been shown in a major study by researchers who also found epigenetic changes in a large number of genes that contribute to reduced insulin production. "This shows that the risk of developing type 2 diabetes is not only genetic, but also epigenetic," said the leading author.

      People with type 2 diabetes have epigenetic changes on their DNA that healthy individuals do not have. 
      This has been shown in a major study by researchers at Lund University.
      The researchers also found epigenetic changes in a large number of genes that contribute to reduced insulin production.

      "This shows that the risk of developing type 2 diabetes is not only genetic, but also epigenetic," said Charlotte Ling, who led the study.

      Epigenetic changes occur as a result of factors including environment and lifestyle, and can affect the function of genes. 

      Charlotte Ling and her colleagues have analysed insulin- producing cells of both healthy individuals and patients with type 2 diabetes. 

      The analysis revealed epigenetic changes in approximately 800 genes in those with type 2 diabetes.

      Over 100 of the genes also had altered expression and many of these could contribute to reduced insulin production. 

      Reduced insulin production is one of the underlying causes of type 2 diabetes.

      In order to work out which is the chicken and which is the egg, i.e. whether the epigenetic changes are a consequence of the disease or if the disease is a result of the changes, the researchers also investigated whether healthy individuals had epigenetic changes caused by age, BMI and raised blood sugar levels.

      "We were able to observe that a number of epigenetic changes had already taken place in healthy subjects as a result of age or high BMI, and were therefore able to conclude that these changes could contribute to the development of the disease," said Charlotte Ling.

      "Unlike genes that can't be changed, epigenetic changes are reversible," added Tasnim Dayeh, first author of the publication in PLOS Genetics.

      Drugs that cause epigenetic changes have long been used in the treatment of cancer and epilepsy. 

      The new survey changes the view of epigenetics in relation to diabetes, according to Charlotte Ling.

      "It shows that epigenetics is of major significance for type 2 diabetes, and can help us to understand why people develop the condition. 

      This also opens the way for the development of future drugs."



      "Introduction

      Type 2 diabetes (T2D) is a complex multifactorial disorder characterized by chronic hyperglycemia due to impaired insulin secretion from pancreatic β-cells, elevated glucagon secretion from pancreatic α-cells and insulin resistance in target tissues.

      As a result of aging populations and an increasing prevalence of obesity and physical inactivity, the number of patients with T2D has dramatically increased worldwide [1]. 

      Family studies together with genome-wide association studies (GWAS) have shown that the genetic background also influences the risk of T2D [2], [3].

      The majority of T2D single nucleotide polymorphisms (SNPs) identified by GWAS are associated with impaired insulin secretion rather than insulin action, pointing to pancreatic islet defects as key mechanisms in the pathogenesis of T2D [3]–[5]. 

      However, the identified SNPs only explain a small proportion of the estimated heritability of T2D, suggesting that additional genetic factors remain to be identified [3].

      Genetic variants can interact with environmental factors and thereby modulate the risk for T2D through gene-environment interactions [6].

      The interaction between genes and environment may also happen through direct chemical modifications of the genome by so called epigenetic modifications, including DNA methylation and histone modifications [7]. 

      These are known to influence the chromatin structure and DNA accessibility and can thereby regulate gene expression [8], [9].

      Epigenetic alterations may subsequently influence phenotype transmission and the development of different diseases, including T2D [7], [10]. 

      Our group has recently found increased DNA methylation in parallel with decreased expression of PPARGC1A, PDX-1 and INS in human pancreatic islets from patients with T2D by using a candidate gene approach [11]–[13]. 

      Another group has analyzed DNA methylation of ~0.1% of the CpG sites in the human genome in pancreatic islets from five T2D and 11 non-diabetic donors [14]. 

      Animal studies further support the hypothesis that epigenetic modifications in pancreatic islets may lead to altered gene expression, impaired insulin secretion and subsequently diabetes [15]–[17]. 

      Although these studies point towards a key role for epigenetic modifications in the growing incidence of T2D, comprehensive human epigenetic studies, covering most genes and regions in the genome in pancreatic islets from diabetic and non-diabetic donors, are still lacking.

      Human studies further need to link T2D associated epigenetic modifications with islet gene expression and eventually impaired insulin and/or glucagon secretion.

      Moreover, the human methylome has previously not been described in human pancreatic islets. In the present study, we analyzed the genome-wide DNA methylation pattern in pancreatic islets from patients with T2D and non-diabetic donors using the Infinium HumanMethylation450 BeadChip, which covers ~480,000 CpG sites in 21,231 (99%) RefSeq genes. 

      The degree of DNA methylation was further related to the transcriptome in the same set of islets.

      A number of genes that exhibited both differential DNA methylation and gene expression in human T2D islets were then selected for functional follow up studies; insulin and glucagon secretion were analyzed in clonal β- and α-cells, respectively where selected candidate genes had been either overexpressed or silenced.

      Also, reporter gene constructs were used to study the direct effect of DNA methylation on the transcriptional activity.

      Together, our study provides the first detailed map of the human methylome in pancreatic islets and it provides new target genes with altered DNA methylation and expression in human T2D islets that contribute to perturbed insulin and glucagon secretion."

      " Human pancreatic islet donors

      Human pancreatic islets from 15 donors with T2D and 34 donors not diagnosed with diabetes were included in the genome-wide analysis of DNA methylation and mRNA expression. 

      Donors were considered to have T2D if they had been diagnosed with the disease prior to their death.

      Selection criteria for non-diabetic donors were to have an HbA1c below 6.0%. 

      Clinical characteristics of these donors are given in Table 1.

      Moreover, the impact of HbA1c levels, age and BMI on DNA methylation was studied in pancreatic islets from 87 non-diabetic donors.

      Their characteristics are given in Table S6.

      Human pancreatic islets were provided by the Nordic Network for Islet Transplantation, Uppsala University, Sweden. "


      Marloes Dekker Nitert <m.dekker@...>,
      Elin Hall <Elin.Hall@...>,
      Anders H. Olsson <Anders_H.Olsson@...>,
      Tina Rönn <Tina.Ronn@...>,
      Tasnim Dayeh <Tasnim.Dayeh@...>,
      Charlotte Ling <charlotte.ling@...>,



      "ADH1 is "unusually highly concentrated" in the million tiny "isles
      of Langerhans" in the pancreas, where the beta cells make insulin --
      cigarette use correlates with diabetes 2 risk, with a doubling of risk
      for smoking over a pack daily.
      [ page 172, "While Science Sleeps", 2012 January, Prof. Woodrow C.
      Monte, Food Science and Nutrition, Arizona State University, retired
      2004 ]

      WhileScienceSleeps.com includes free online archive of 745 full
      text medical research references:





      " #6 diabetes 2 risk high for 2 cans aspartame diet drink weekly 14
      years 66K women study, Guy Fagherazzi et al AJCN 2013 Jan -- methanol
      (cigarettes, aspartame) formed into formaldehyde inside cells in
      pancreas by ADH1 enzyme, WC Monte paradigm: Rich Murray 2013.02.13


      The WC Monte January 2012 text is available at Amazon.com, "While
      Science Sleeps", low cost ebook,  backed by his online archive of 745
      free full text medical research references at WhileScienceSleeps.com ,
      while two full chapters are free: Chapter 9, "Multiple Sclerosis" and
      12, "Autism and Other Birth Defects."


      ADH1 is "unusually highly concentrated" in the million tiny "isles
      of Langerhans" in the pancreas, where the beta cells make insulin --
      cigarette use correlates with diabetes 2 risk, with a doubling of risk
      for smoking over a pack daily.
      [ page 172, "While Science Sleeps", 2012 January, Prof. Woodrow C.
      Monte, Food Science and Nutrition, Arizona State University, retired
      2004 ]

      WhileScienceSleeps.com includes free online archive of 745 full
      text medical research references:



      Bühler R., Pestalozzi D., Hess M., Von Wartburg JP.
      Immunohistochemical localization of alcohol dehydrogenase in human
      kidney, endocrine organs and brain.
      Pharmacol Biochem Behav. 1983;
      18 Suppl 1:55-9 1983;18(Suppl 1):55-9.

      Willi C., Bodenmann P., Ghali WA., Faris PD., Cornuz J.
      Active smoking and the risk of type 2 diabetes: a systematic review
      and meta-analysis.
      JAMA 2007;298(22):2654-64.

      Wei M, Gibbons L, Mitchell T, Kampert J, Blair S.
      Alcohol intake and incidence of type 2 diabetes in men.
      Diabetes Care 2000;23(1):16-21. Ming Wei mwei@... ]


      Many of these diseases, including diabetes 2, are twice as harmful for
      those who never drink ethanol, compared to those who have just one
      standard drink a day, due to the inhibition by ethanol of formation of
      formaldehyde from methanol by ADH1.

      Many people are protected by methanol in their blood from fermentation
      by bacteria in the GI tract. "



      Table 5.2 is the key chart -- ADH1 enzyme at high levels in 20 tissues
      in body and fetus makes methanol into formaldehyde right inside cells,
      initiating over 20 human diseases, with full text references, WC Monte
      paradigm: Rich Murray 2013.03.21


      [ See also:,
      2013.03.13  292,095 visits in a week ]

      [ welcome to a scientific bouquet -- some tasty dishes are presented twice... ]

      A liter of diet drink gives the same methanol (wood alcohol) as the
      smoke from a pack of cigarettes, 60 mg -- methanol has a half-life in
      the human bloodstream of 3 hours, showing that its elimination is
      slow, while it reaches every part of the body and the fetus every
      minute.

      Methanol is actually less toxic than ethanol, except when it goes
      easily into cells that also happen to have high levels of free
      floating ADH1 enzyme, in 19 specific human tissues, including inner
      walls of blood vessels in the brain and eye, as well as in the rods
      and cones of the retina -- the methanol is made quickly into free
      floating formaldehyde inside these cells, where it naturally wrecks
      havoc, interfering with all biochemistry, just as in its well known
      uses for embalming and sterilizing medical tools.

      The resulting stew of formaldehyde modified proteins activates the
      inflammation process of the immune system, producing complex evolving
      pussy lesions -- brain in Alzheimer's and multiple sclerosis, inner
      walls of blood vessels in atherosclerosis, skin fibroblasts in lupus,
      pancreas in diabetes 2, retina in macular degeneration, joint
      fibroblasts in rheumatoid arthritis...

      Methylation of DNA and RNA leads to cell dysfunction and death, many
      later cancers, and birth defects, spina bifida, autism, preterm birth,
      Fetal Alcohol Sydrome.

      Two key ATP enzymes are impaired in mitochrondria, shutting down
      aerobic energy metabolism, leading to reduced metabolism and anaerobic
      buildup of lactic acid, resulting in acidosis.



      Table 5.2: Target Organs of Methanol Toxicity (Bad ADH1 Sites)
      pages 60-1 "While Science Sleeps" textbook 2012 January, 236 pages,
      Chapter 5 "The Silent Battle That Turns Methanol into Disease" --

      the key chart that summarizes how ADH1 enzyme in high levels in 20
      tissues in body and fetus makes methanol into formaldehyde right
      inside cells, initiating over 20 human diseases:


      7 ADH1 references (listed below) for 16 tissue types (some tissues
      have several diseases)  218, 220, 221, 357, 503, 514, 563, 637, 638,
      640;

      18 target tissues for formaldehyde harm;

      over 20 specific modern novel "diseases of civilization";

      each with huge growth in incidence in the last 35 years -- 25 references;

      U shaped curve (those who never drink ethanol get twice the harm for 6
      of these diseases as those who drink once daily, since ethanol is a
      potent antidote that prevents ADH1 from making methanol into
      formaldehyde) -- 8 references;

      18 diseases from smoking cigarettes (a strong methanol source)  -- 24
      references;

      13 diseases from using aspartame -- 22 references;

      Monte didn't have enough room on this 2-page figure to include the
      suite of 12 of the same symptoms and tissues from cases of often fatal
      chronic and acute methanol toxicity, page 133, with copious
      references.

      This is a work in progress, highly incomplete, as this is an
      introductory update on the status of an breakthrough paradigm in
      toxicology, that presents multiple strong lines of evidence, allowing
      any intelligent layperson to come to their own decisions about
      methanol and resulting chronic formaldehyde toxicity diseases for
      specific high ADH1 sites, ranging from breast cancer to diabetes 2.

      Table 5.2: target organs of methanol toxicity (bad ADH1 sites) [ edited ]

      brain, vascular tissue,
      tau protein  -- Alzheimer's
      myelin basic protein -- multiple sclerosis
      vascular lining -- headache, seizures, glioblastoma cancer

      eye, retina, ADH1 in rods and cones -- macular degeneration

      blood vessels, intima and media (inner walls),
      LDL low density lipoproteins -- atherosclerosis

      skin, fibroblasts -- skin cancer, dermatitis, lupus (SLE systemic
      lupus erythematosus)

      breast, epithelial (milk ducts) -- adenocarcinoma

      kidney, epithelial tubule -- kidney cancer, poor function

      bone, synovial fibroblast -- rheumatoid arthritis

      pancreas, islets of Langerhans -- reduced insulin,  diabetes 2

      lung, fibroblasts -- COPD chronic obstructive pulmonary disease, adenocarcinoma

      fetus, no ADH1 in placenta,
      DNA methylation -- terata (birth defects), autism
      liver, lung, kidney harm -- preterm delivery

      liver, highest ADH1 in body, many targets -- hepatic cancer


      "While Science Sleeps" textbook, 2012 January:

      "Methanol travels easily to breast tissue and has been found in human milk. 219

      The cells that produce milk within the breast, cells prone to develop
      the most common of breast cancers, adenocarcinoma 358, contain high
      levels of ADH1 enzyme, 358 allowing methanol's conversion to
      formaldehyde [ inside the cells as free floating acidic hydrated
      formaldehyde, highly reactive on both sides of molecule ].

      Mammary epithelial cells have no way to protect themselves from
      formaldehyde 216 -- no means to render it harmless.

      They, unlike other breast tissue, contain no aldehyde dehydrogenase
      enzyme (ADH 3) that could transform formaldehyde into the
      non-carcinogenic formic acid. 216

      Of particular interest are recent findings implicating ADH as playing
      a pivotal role in the formation of breast cancer, documenting a
      greater incidence of the disease in women with higher levels of ADH1
      activity in their breasts. 357"


      Labreche F, Goldberg M.
      Exposure to Organic Solvents and Breast Cancer in Women: A Hypothesis.
      American Journal of Industrial Medicine 1997;32:1-14.

      Triano E, Slusher L, Atkins T, Beneski J, Gestl S.
      Class I Alcohol Dehydrogenase Is Highly Expressed in Normal Human
      Mammary Epithelium but not in Invasive Breast Cancer: Implications for
      Breast Carcinogenesis.
      Cancer Research Arch 2003;63:3092-100.

      Crabb D, Matsumoto M, Chang D, You M.
      Overview of the role of alcohol dehydrogenase and aldehyde
      dehydrogenase and their variants in the genesis of alcohol-related
      pathology.
      Proceedings of the Nutrition Society 2004;63:49-63.

      Coutelle C.
      Risk Factors in Alcohol Associated Breast Cancer: Alcohol
      Dehydrogenase Polymorphism and Estrogens.
      International Journal of Oncology 2004;25:1127-32.


      #6 diabetes 2 risk high for 2 cans aspartame diet drink weekly 14
      years 66K women study, Guy Fagherazzi et al AJCN 2013 Jan -- methanol
      (cigarettes, aspartame) formed into formaldehyde inside cells in
      pancreas by ADH1 enzyme, WC Monte paradigm: Rich Murray 2013.02.13


      The WC Monte January 2012 text is available at Amazon.com, "While
      Science Sleeps", low cost ebook,  backed by his online archive of 745
      free full text medical research references at WhileScienceSleeps.com ,
      while two full chapters are free: Chapter 9, "Multiple Sclerosis" and
      12, "Autism and Other Birth Defects."


      ADH1 is "unusually highly concentrated" in the million tiny "isles
      of Langerhans" in the pancreas, where the beta cells make insulin --
      cigarette use correlates with diabetes 2 risk, with a doubling of risk
      for smoking over a pack daily.
      [ page 172, "While Science Sleeps", 2012 January, Prof. Woodrow C.
      Monte, Food Science and Nutrition, Arizona State University, retired
      2004 ]

      WhileScienceSleeps.com includes free online archive of 745 full
      text medical research references:



      Bühler R., Pestalozzi D., Hess M., Von Wartburg JP.
      Immunohistochemical localization of alcohol dehydrogenase in human
      kidney, endocrine organs and brain.
      Pharmacol Biochem Behav. 1983;
      18 Suppl 1:55-9 1983;18(Suppl 1):55-9.

      Willi C., Bodenmann P., Ghali WA., Faris PD., Cornuz J.
      Active smoking and the risk of type 2 diabetes: a systematic review
      and meta-analysis.
      JAMA 2007;298(22):2654-64.

      Wei M, Gibbons L, Mitchell T, Kampert J, Blair S.
      Alcohol intake and incidence of type 2 diabetes in men.
      Diabetes Care 2000;23(1):16-21. Ming Wei mwei@... ]


      Many of these diseases, including diabetes 2, are twice as harmful for
      those who never drink ethanol, compared to those who have just one
      standard drink a day, due to the inhibition by ethanol of formation of
      formaldehyde from methanol by ADH1.

      Many people are protected by methanol in their blood from fermentation
      by bacteria in the GI tract.


      high levels of ADH1:

      liver, kidney, lung;
      intima and media (inner walls) of blood vessels, notably base of brain
      and retina;
      rods and cones in retina;
      purkinje cells of vermis in cerebellum;
      islets of Langerhans in pancreas;
      fibroblasts in skin, bone marrow, synovial tissues in joints;
      milk ducts of breast;


      Men have several times more ADH1 in their GI tract than women, so less
      methanol gets into the blood to attack other tissues, so now four
      times as many women get multiple sclerosis as men.


      sources of methanol (wood alcohol):

      smoke from cigarettes, wood, peat;

      aspartame, and chewing gums;

      some dark wines and liquors;

      fresh tomatoes, black currants;

      unfresh fruits juices vegetables cut up and preserved wet at room
      temperature in sealed cans jars plastic containers (including home
      preserves and jugs of apple cider by farming families);

      jams jellies marmalades;

      smoked fermented spoiled foods;

      some fresh coffees;

      approved food additive dimethyl dicarbonate;

      vehicle fuels;

      medical chemical mortuary facilities, home and industry solvents,
      factories for processed wood and paper products -- formaldehyde heated
      to 150 deg C releases methanol...


      Eng L. Localizations of Spacific Brain Antigens.
      In: Boese A, editor. Search for the Cause of Multiple Sclerosis and
      other Chronic Diseases of the Central Nervous System.
      Basel: Verlag Chemie; 1980. p. 15-460.

      Search for the cause of multiple sclerosis and other chronic diseases
      of the central nervous system:
      1. internat. symposion of Hertie Foundation in Frankfurt/Main,
      September 1979 / ed. by A.
      Boese. — Weinheim, Deerfield Beach (Florida), Basel: Verlag Chemie, 1980.
      ISBN 3-527-25875-2  [ 38 pages from a variety of reports in 460 page
      collection ]

      Dr. Alfred Boese
      GemeinnOtzige Hertie-Stiftung
      Lyoner StraBe 15
      D-6000 Frankfurt 71


      Mori O, Haseba T, Kameyama K, Shimizu H.
      Histological distribution of class III alcohol dehydrogenase in human brain.
      Brain Research 2000;852:186-90. 5 pages

      Allili-Hassani A, Martinez S, Peralba J., et al.
      Alcohol dehydrogenase of human and rat blood vessels:
      role in ethanol metabolism.
      FEBS Letters 1997;405:26-30.  5 pages

      Buehler R, Hess M, Wartburg J.
      Immunohistochemical Localization of Human Liver Alcohol Dehydrogenase
      in Liver Tissue, Cultured Fibroblasts, and HeLa Cells.
      American Association of Pathologists 1982;108(1):89-99.   11 pages

      Coutelle C.
      Risk Factors in Alcohol Associated Breast Cancer:
      Alcohol Dehydrogenase Polymorphism and Estrogens.
      International Journal of Oncology 2004;25:1127-32.
      [ 1 page news report ]
      Coutelle C, Höhn B, Benesova M, Oneta CM, Quattrochi P, Roth HJ,
      Schmidt-Gayk H, Schneeweiss A, Bastert G, Seitz HK.
      Department of Medicine
      and Laboratory of Alcohol Research, Liver Disease and Nutrition,
      Salem Medical Centre, Heidelberg, Germany.
      6 pages

      Estonius M, Svensson S, Höög J.
      Alcohol dehydrogenase in human tissues:
      localisation of transcripts coding for five classes of the enzyme.
      FEBS Lett. 1996;397:338-42.  5 pages

      Kinne R, Bräuer R, Stuhlmüller B, Palombo-Kinne E, Burmeste GR.
      Macrophages in rheumatoid arthritis.
      Arthritis Res 2000;2(3):189-202.  14 pages
      [ no mention of ADH1 -- the cause of RA is unknown... ]

      Scott B, Weisbrot L, Greenwood J, Bogoch E, Paige C, Keystone E.
      Rheumatoid Arthritis Synovial Fibroblast and U937 Macrophage/Monocyte
      Cell Line Interaction In Cartilage Degradation.
      ARTHRITIS &amp; RHEUMATISM, American College of Rheumatology.
      1997;40(3):490-98. 9 pages
      [ a lab in vitro model of cartilage degradation did not mention ADH1
      -- some findings were puzzling. ]

      Petersen BJ., Cornell NW., Veech RL.
      Alcohol dehydrogenase in cultured human skin fibroblasts.
      Human fibroblast alcohol dehydrogenase.
      Adv Exp Med Biol 1980;132:533-41. [ abstract ]

      Smith M., Hopkinson DA., Harris H.
      Developmental changes and polymorphism in human alcohol dehydrogenase.
      Ann Hum Genet 1971;34(3):251-71.   [ abstract ]


      WC Monte finally got secret FDA memo 37 years after Searle Co. labs
      found birth defects in rabbits from aspartame (methanol, becomes
      formaldehyde via ADH1 enzyme within human cells) and its
      phenylalanine: Rich Murray 2012.06.02


      highly competent, pithy analysis of aspartame cancer study by Eva S.
      Schernhammer at Harvard, William R. Ware, PhD, showing relevance of
      Woodrow C. Monte methanol-formaldehyde toxicity paradigm: Rich Murray
      2012.12.03


      confirms WC Monte paradigm: ingested methanol becomes toxic
      formaldehyde-induced hydroxymethyl DNA adducts in all tissues in rats,
      sensitive C13 test, Kun Lu, James A Swenberg, UNC Chapel Hill
      2011.12.08 Toxicol Sci: Rich Murray 2013.01.11


      WSS p. 172 reference 297
      [ While Science Sleeps textbook, 2012 January, Prof. Woodrow C. Monte,
      Food Science and Nutrition, Arizona State University, retired 2004 --
      free online archive of 745 full text medical research references
      WhileScienceSleeps.com ]

      WSS:
      "Most startling and provocative of all was a report evaluating the
      long term symptomology of over three thousand patients with type I
      diabetes.
      The complications of long term type I diabetes are retinopathy (damage
      to the retina of the eye), neuropathy and vascular complications, all
      of which we have discussed as associated with methanol toxicity.
      This study showed that moderate alcohol consumption in these
      individuals protected against all of these complications by a
      protective factor of as much as three times compared to non-alcohol
      consumers in what the researchers concluded was a "U-shaped
      fashion."297



      Diabetologia. 2008 Sep;51(9):1631-8. doi: 10.1007/s00125-008-1091-z.
      Epub 2008 Jul 15.
      Alcohol consumption and risk of microvascular complications in type 1
      diabetes patients: the EURODIAB Prospective Complications Study.
      Beulens JW &lt; J.Beulens@...&gt;,
      Kruidhof JS,
      Grobbee DE,
      Chaturvedi N,
      Fuller JH,
      Soedamah-Muthu SS.
      Julius Center for Health Sciences and Primary Care,
      University Medical Center Utrecht,
      Room STR 6.131, P.O. Box 85500,
      3508 GA, Utrecht, The Netherlands.

      Abstract

      AIMS/HYPOTHESIS:
      The aim of this study was to investigate the association between
      alcohol consumption and risk of microvascular complications
      (retinopathy, neuropathy, nephropathy) in type 1 diabetes mellitus
      patients in the EURODIAB Prospective Complications Study.

      METHODS:
      The EURODIAB Prospective Complications Study is a follow-up study
      including 3,250 type 1 diabetes mellitus patients from 16 different
      European countries.
      We investigated the cross-sectional association between moderate
      alcohol consumption and risk of retinopathy, neuropathy and
      nephropathy among 1,857 of these patients.

      RESULTS:
      We documented 304 cases of proliferative retinopathy,
      660 cases of neuropathy and
      157 cases of nephropathy (macroalbuminuria).

      Alcohol consumption was associated with risk of proliferative
      retinopathy, neuropathy and macroalbuminuria in a U-shaped fashion.
      Moderate consumers (30-70 g alcohol per week)
      [ 5 to 10 gram daily = 2.5 to 5 tsp 80 proof vodka ]
      had a lower risk of microvascular complications with odds ratios of
      0.60 (95% CI 0.37-0.99) for proliferative retinopathy,
      0.61 (0.41-0.91) for neuropathy and
      0.36 (0.18-0.71) for macroalbuminuria
      in multivariate-adjusted models.
      These results were similar when excluding patients who had been
      advised to drink less alcohol because of their health.
      The relation was most pronounced for alcohol consumption from wine.
      Drinking frequency was significantly, inversely associated with risk
      of neuropathy, but a similar trend was visible for proliferative
      retinopathy and macroalbuminuria.
      Alcohol consumption was not associated with occurrence of ketoacidosis
      or hypoglycaemic attacks.

      CONCLUSIONS/INTERPRETATION:
      Consistent with its effects on macrovascular complications, moderate
      alcohol consumption is associated with a lower risk of all
      microvascular complications among type 1 diabetes patients.

      PMID: 18626626


      fetal alcohol syndrome, 1/1000 births, new MRI science shows specific
      brain harm in kids,  Andrzej Urbanik, Poland -- could confirm Woodrow
      C. Monte methanol-formaldehyde toxicity paradigm: Rich Murray
      2012.11.26
      [ excerpts ]


      methanol (11% of aspartame), made by body into formaldehyde in many
      vulnerable tissues, causes modern diseases of civilization, summary of
      a century of research, Woodrow C Monte PhD, Medical Hypotheses
      journal: Rich Murray 2009.11.15
      Sunday, November 15, 2009

      "Formaldehyde produced within the cell immediately reacts with water
      to produce formal hydrate,[#27] a strong acid[#114] with twice the
      number of available hydrogen ions as the next methanol metabolite,
      formic acid.

      Formal hydrate produced from methanol by the ADH I sites found in
      the intima, media, and adventitia lining of the circulatory system of the
      heart and brain[#220] would be expected to diffuse into the localized
      tissue, quickly methylating basic molecules such as myelin basic
      protein (MS)[#224] and tau protein (Alzheimer's).[#234]"

      free full text, 5 pages
      Monte WC.
      Methanol: A chemical Trojan horse as the root of the inscrutable U.
      Med Hypotheses 2010;74(3):493-6.

      Methanol: A Chemical Trojan Horse as the Root of the Inscrutable U
      Prepublication Copy; Medical Hypotheses -- 06 November 2009
      (10.1016/j.mehy.2009.09.059)
      Woodrow C. Monte PhD
      [ extracts ]

      The Hypothesis:

      Formaldehyde produced from dietary and environmental methanol
      metabolized in situ at the non-hepatic sites of class I alcohol
      dehydrogenase (ADH I) may play a role in many diseases of
      civilization (DOC).

      Ethanol may in turn act as a competitive inhibitor of methanol's
      conversion to formaldehyde by ADH I, as reflected in the
      U-shaped curve of alcohol consumption.

      Discussion:

      July 24, 1981, should be a significant date for scientists investigating
      worldwide epidemics of Alzheimer's disease (AD),[#540],[#533]
      multiple sclerosis (MS),[#77],[#214] atherosclerotic cardiovascular
      disease (ACD),[#532] lupus,[#536] skin[#95] and breast cancer,
      [#250],[#193] autism,[#525] and other diseases of civilization
      (DOC).

      On this date the U.S. Food and Drug Administration approved the
      use of aspartame,[#472] a new artificial sweetener.[#473]
      As aspartame eventually became a major source of methanol in the
      civilized human diet,[#1] the incidence of DOC gradually began to
      rise.

      Rarely found in nature and an insignificant component of the diets of
      Pleistocene man and present-day foragers, methanol has been
      increasing incrementally in the diet of civilized humanity since 1806
      when Nicolas Appert commercialized canning, a process that traps
      methanol derived from the heating and storage of plant materials
      containing pectin.[#1]

      In addition to aspartame, and canned vegetables, fruits, and their
      juices,[#28],[#29] a major source of the methanol entering the
      modern civilized human body is cigarette smoke,[#62]
      causatively linked to atherosclerosis, multiple sclerosis,[#68]
      lupus,[#73] Alzheimer's disease,[#535] rheumatoid arthritis,[#332]
      and other DOC.[#345]

      A poison to which humans are particularly sensitive,[#3] methanol
      was responsible for the loss of hundreds of lives at the beginning of
      the twentieth century[#17] when extensive animal testing determined
      it was safer than ethanol, allowing its first use in foods and
      drugs.[#165]
      Because the toxicity of methanol in the human system cannot be
      properly tested in animals, the results of this research were specious.

      Searching for the cause of the metabolic anomaly that makes the
      human relationship to methanol distinct from all laboratory animal
      models, including primates,[#116] has always been muddied by
      industrial agendas[#39] with a vested interest in proving that the
      formaldehyde produced from methanol in the human body does no
      harm.[#40],[#121]
      The prevalence of compromised literature and the lack of an
      applicable animal model may explain why methanol, which fits many
      of the criteria of availability and stealth that one would expect of a
      usual suspect, has not yet caught the attention of scientists searching
      for the elusive etiologic agent of DOC.
      The single article that posits methanol as the possible direct cause of
      multiple sclerosis[#8] is never cited in the MS literature.

      A recent series of comprehensive in-vitro studies has also
      convincingly linked Alzheimer's disease to very low concentrations of
      formaldehyde.
      This research mentions methanol as a possible in vivo source,[#234],
      [#235] but significantly, it neglects to stress the fact that there is no
      simpler way for formaldehyde to get past the blood brain barrier
      than in the form of this smallest of alcohols.[#367]

      Methanol is itself harmless but is a Trojan horse for formaldehyde,
      a chemical that can pose a severe risk to humans,[#7] who appear
      to be the only mammal exclusively endowed with a hepatic catalase
      enzyme incapable of removing dietary methanol before it can enter
      the general circulation.[#52]

      Once methanol runs the gauntlet of first-pass metabolism, its
      detoxification is no longer exclusive to the liver.

      Formaldehyde, the first metabolite of methanol, can then be
      produced within the arteries and veins,[#220] heart,[#503]
      brain,[#218] lungs,[#221] breast,[#358] bone,[#503]
      and skin.[#221]

      These major organs harbor extra hepatic sites of the only remaining
      human enzyme capable of metabolizing methanol,
      class I alcohol dehydrogenase (ADH I).[#112]

      Methanol transports its potential to become formaldehyde past
      normal biological barriers in the brain and elsewhere that
      environmental formaldehyde itself cannot usually penetrate.[#122]

      That formaldehyde produced in these organs from methanol has
      not been detected directly in humans should not be surprising since
      formaldehyde vanishes within minutes, binding to
      macromolecules[#114] even when a solution of it is injected directly
      into tissue[#122] or spiked into cell-free human serum.[#236]

      Although methylation caused by this toxic process could be
      functionally destructive to the macromolecule so modified, the
      addition of methyl groups to large molecules renders the modification
      and its source invisible to any clinical or histological testing
      procedure.[#122],[#236]

      However, in a study by Trocho et al., a portion of the C14 labeled
      methanol moiety of aspartame was shown to bind to such
      macromolecules via formaldehyde and not pass directly into the
      one-carbon cycle via formate as predicted by the generally accepted
      model of methanol toxicity,[#40] a model developed from studying
      the severe methanol poisoning of monkeys, not the chronic
      environmental exposure of humans.

      Formate derived from methanol metabolism is never measurable in
      human blood when small environmentally reflective doses of methanol
      are administered.[#42]
      During acute methanol poisoning, where the methanol concentration
      of the portal vein far exceeds that of ethanol, liver ADH I would be
      saturated with methanol.

      The liver's ample supply of aldehyde dehydrogenase would assure
      production of formic acid, which is metabolized very slowly,
      causing leakage of formate into the general circulation.
      Formate is not, however, a significant poison to humans and has,
      in fact, been used therapeutically and as a food additive.[#365]

      It certainly would be more convenient to have a stable, measurable
      entity such as formate to predict the danger of exposure to methanol,
      but an iron-clad case for the toxicological significance of this much
      less toxic, secondary metabolite has not yet been made.[#55]

      Moreover, the results of Trocho's elegant study should give one
      pause before accepting the widely held premise that formate and
      not formaldehyde is the toxic component of methanol poisoning.

      Laboratories that publish the most cited works are often financially
      supported by industries with much to lose were the safety of methanol
      disproved.
      This research must be carefully reconsidered before we can dismiss
      the potential threat posed by formaldehyde strategically placed by
      dietary methanol.

      Formaldehyde produced within the cell immediately reacts with water
      to produce formal hydrate,[#27] a strong acid[#114] with twice the
      number of available hydrogen ions as the next methanol metabolite,
      formic acid.

      Formal hydrate produced from methanol by the ADH I sites found in
      the intima, media, and adventitia lining of the circulatory system of the
      heart and brain[#220] would be expected to diffuse into the localized
      tissue, quickly methylating basic molecules such as myelin basic
      protein (MS)[#224] and tau protein (Alzheimer's).[#234]

      Such changes have been shown in these disease states.
      Formaldehyde, also known to uncouple oxidative phosphorylation
      and inhibit phosphorylation within cells,[#113] could contribute to
      these changes reported in MS[#224] and Alzheimer's.[#506]

      The immune system reacts swiftly to methylation of protein by
      formaldehyde -- a phenomenon put to good use by the vaccine
      industry for the last hundred years.[#26]

      Macrophages have activation sites specifically for formaldehyde
      modified protein[#23] and are well known to have a ravenous
      appetite for LDLs reacted with small aldehydes.[#507]

      This induces the esterification of phagocytized LDL cholesterol and
      the subsequent transformation of the macrophages to
      foam cells,[#508] similar to the sequence of events leading to
      atheroma production adjacent to the intima layer of the human aorta,
      rich in ADH I.[#220]

      The potential for antibody production against methylated self-protein
      phagocytized by macrophages has never been investigated.

      Ethanol in low concentrations acts as a powerful competitive
      inhibitor[#439] with a 16:1 preference for ethanol to acetaldehyde
      over the conversion of methanol of formaldehyde by ADH I.[#389]
      For this reason, ethanol is used, without FDA approval, as the
      preferred antidote for accidental methanol poisoning in emergency
      rooms throughout the world.[#253]

      Very low levels of ethanol in the bloodstream would substantively
      prevent all formaldehyde production from dietary methanol
      anywhere in the body.

      Protection from formaldehyde production may account for the yet
      unexplained dose region of apparent improvement in the
      U-shaped curve of alcohol consumption.
      Epidemiologic studies show moderate consumption of alcohol is
      associated with a reduced risk of myocardial infarction,[#485]
      dementia,[#534] lupus,[#73] and other DOC.

      Low doses of ethanol appear to provide a preventative measure
      against the causes of DOC.[#279]
      Recent studies of individuals who consumed at least one alcoholic
      drink per day show subjects had an additional 86 percent
      reduction in risk of myocardial infarction if they were genetically
      endowed with a genotype of ADH I that was 2.5 times slower to
      metabolize ethanol than the control
      These findings were "consistent with the hypothesis that a slower
      rate of clearance of alcohol enhances the beneficial effect of
      moderate alcohol consumption on the risk of cardiovascular
      disease."[#483]

      A compelling explanation of the dose region of adverse effects of
      the U-shaped curve with high ethanol consumption, which shows
      increased risk of these same diseases, could be the mechanism by
      which humans habituate to high consumption of ethanol.

      The induction of the P450 hepatic microsomal ethanol oxidizing
      system[#175] results in a considerably higher clearance rate of
      ethanol from the bloodstream for an extended period of time, thus
      accounting for more consumption leading to statistically less time
      of protection.
      Small amounts of supplemental alcohol not sufficient to induce
      P450 might be expected to prolong the residence time and avoid
      gaps in the protection afforded by ethanol in preventing methanol
      placed formaldehyde.

      It appears that the average person, whether or not an imbiber,
      may typically have endogenous ethanol in the blood[#174]
      produced by gut fermentation.[#363]
      This ethanol must pass through the liver via the hepatic portal vein
      coincidently with dietary methanol absorbed from the gut contents.
      The liver has the highest concentration of ADH I in the body.

      Even traces of ethanol in the blood, however, would seem to
      indicate the absence of available sites remaining for the oxidation
      of the much less competitive methanol, allowing most dietary
      methanol to pass freely into the general circulation.

      What follows is a biochemical game of musical chairs as methanol
      travels round and round the circulation, waiting for the ethanol levels
      to reach zero and the music to stop.
      The closest ADH I free to service the methanol will convert it to
      formaldehyde. If this happens in the liver, where there are ample
      supplies of aldehyde dehydrogenase, metabolism to carbon dioxide
      will proceed safely.

      In mammary epithelium, however,
      where human class I alcohol dehydrogenase is highly expressed[#358]
      but active aldehyde dehydrogenase[#216] is scarce, methanol placed
      formaldehyde could become a problem.

      Formaldehyde is a class I carcinogen[#11] and mutagen[#449]
      with methanol providing its only easy avenue into this tissue.

      In the vasculature of the brain[#218] and other ADH I positive
      organs, the consequences may be similarly troublesome.

      The obvious way to prevent formaldehyde from damaging this
      sensitive tissue is to keep the music playing, a solution dependent
      on our ability to answer the following questions:
      Just how much ethanol is essential in this seemingly inscrutable
      U-shaped curve?
      What measures should we take to combat this chemical Trojan horse,
      thereby reducing the methanol contamination in the diet of civilization
      and making it more like the diet of our ancient ancestors?


      Methyl alcohol ingestion as a model etiologic agent in multiple
      sclerosis, WC Monte, D Glanzman, C Johnston; Methanol induced
      neuropathology in the mammalian central nervous system, Woodrow C.
      Monte, Renee Ann Zeising, both reports 1989.12.04: Murray 2007.12.28
      2012.05.01


      Aspartame: The hidden danger [methanol/formaldehyde] in our midst and
      how it kills us, 12 page review of While Science Sleeps text (Woodrow
      C Monte), International Health News, whole June issue, Editor: William
      R Ware PhD: Rich Murray 2012.06.08

      [ much more... ]


      careful expert lifetime study on mice shows liver and lung cancers
      from aspartame, M Soffritti et al, Ramazzini Institute, Italy, checked
      by US National Toxicology Program experts, confirms many previous
      studies from 2001 on: Rich Murray 2011.02.27
      http://rmforall.blogspot.com/ 2011/02/careful-expert- lifetime-study-on-mice.html
      http://health.groups.yahoo. com/group/aspartameNM/message/ 1619



      Prof. Erik Millstone 2013.12.16 crisp critique of EFSA blatant pro-industry bias on 2013.12.10 aspartame decision --  Sepp Hasslberger blog: Rich Murray 2014.01.07
      http://rmforall.blogspot.com/ 2014/01/prof-erik-millstone- 20131216-crisp.html


      research on aspartame (methanol, formaldehyde, formic acid) toxicity: Rich Murray 2004.07.11 2014.01.21
      http://rmforall.blogspot.com/ 2014/01/research-on-aspartame- methanol.html
      http://groups.yahoo.com/group/ aspartameNM/message/1806 part 1 of 2
      http://groups.yahoo.com/group/ aspartameNM/message/1809 part 2 of 2
      http://groups.yahoo.com/group/ aspartameNM/message/1100  original


      "As a matter of course, every soul citizen of Earth has a priority to quickly find and positively share evidence for healthy and safe food, drink, environment, and society."

      within the fellowship of service,

      Rich Murray,
      MA Boston University Graduate School 1967 psychology,
      BS MIT 1964 history and physics,
      254-A Donax Avenue, Imperial Beach, CA 91932-1918


    Your message has been successfully submitted and would be delivered to recipients shortly.