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two recent warning studies on stevia toxicity on rats and bacteria, AP Nunes et al, 2007 April, 2006 Dec, links to 18 positive abstracts from 2000 February to 2004 January: Murray 2007.05.03

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  • rmforall@comcast.net
    two recent warning studies on stevia toxicity on rats and bacteria, AP Nunes et al, 2007 April, 2006 Dec, links to 18 positive abstracts from 2000 February to
    Message 1 of 1 , May 3 4:42 PM
      two recent warning studies on stevia toxicity on rats and bacteria, AP
      Nunes et al, 2007 April, 2006 Dec, links to 18 positive abstracts from
      2000 February to 2004 January: Murray 2007.05.03
      http://groups.yahoo.com/group/aspartameNM/message/1419

      At the end of this post, I link to my 5 previous reviews in 2005
      August that give 18 full abstacts in PubMed on stevia toxicity from
      2000 February to 2004 January, which do not find that stevia is
      practically toxic to humans in ordinary use -- and give an opposite
      positive abstract using the Comet assay in 2002 December, and then
      share the conclusion from the full text of another study on
      mutagenicity, T Terai et al 2002 July.


      These two recent studies by a reputable mainstream academic research
      team in Brazil, who publish similar toxicity studies on other
      chemicals, used rats and bacteria to find negative effects, which
      justify additional careful studies, to decide if the approval of
      stevia should be reversed in Japan, South Korea, China, Brazil, and
      Paraguay, or the maximum lifetime safe dose be set at a lower level.

      The other recent studies on stevia in PubMed since 2004 January
      include no negative safety studies and many about possible positive
      therapeutic effects. I'm not going to try to master this expanding
      and complex field, but just provide some useful orientation. Every
      citizen has to find their own strategy for making practical decisions
      about risk, and assessing information sources.

      In mutual service, Rich Murray


      Food Chem Toxicol. 2007 Apr; 45(4): 662-6. Epub 2006 Oct 27.
      Analysis of genotoxic potentiality of stevioside by comet assay.

      * Nunes AP,
      * Ferreira-Machado SC,
      * Nunes RM,
      * Dantas FJ,
      * De Mattos JC,
      * Caldeira-de-Araujo A.

      Departamento de Biofisica e Biometria, Universidade do Estado do
      Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Av 28
      de Setembro, 87, 20551-030 Rio de Janeiro, RJ, Brazil.

      Stevioside is a natural non-caloric sweetener extracted from
      Stevia rebaudiana (Bertoni) leaves.

      It has been widely used in many countries, including Japan, Korea,
      China, Brazil and Paraguay,
      either as a substitute for sucrose in beverages and foods or as a
      household sweetener.

      The aim of this work was to study its genotoxic potentiality in
      eukaryotic cells.

      Wistar rats were treated with stevioside solution (4mg/mL) through
      oral administration (ad libitum) and the DNA-induced damage was
      evaluated using the single cell gel electrophoresis (comet assay).

      The results showed that treatment with stevioside generates lesions in
      peripheral blood, liver, brain and spleen cells in different levels,
      the largest effect being in liver.

      Therefore, these undesired effects must be better understood, once the
      data present here point to possible stevioside mutagenic properties.
      PMID: 17187912



      Mol Cell Biochem. 2006 Dec; 293(1-2):187-92. Epub 2006 Jun 28.
      Biological effects of stevioside on the survival of Escherichia
      coli strains and plasmid DNA.

      * Nunes AP,
      * De Mattos JC,
      * Ferreira-Machado SC,
      * Nunes RM,
      * Asad NR,
      * Dantas FJ,
      * Bezerra RJ,
      * Caldeira-de-Araujo A.

      Departamento de Biofisica e Biometria, Universidade do Estado do
      Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Avenida
      28 de Setembro #87, Rio de Janeiro, RJ 20551-030, Brazil.

      Stevioside is widely used daily in many countries as a non-caloric
      sugar substitute.

      Its sweetening power is higher than that of sucrose by approximately
      250-300 times, being extensively employed as a household sweetener, or
      added to beverages and food products.

      The purpose of this study was to ascertain stevioside genotoxic and
      cytotoxic potentiality in different biological systems, as its use
      continues to increase.

      Agarose gel electrophoresis and bacterial transformation were employed
      to observe the occurrence of DNA lesions.

      In addition to these assays, Escherichia coli strains were incubated
      with stevioside so that their survival fractions could be obtained.

      Results show absence of genotoxic activity through electrophoresis and
      bacterial transformation assays and drop of survival fraction of E.
      coli strains deficient in rec A and nth genes, suggesting that
      stevioside
      (i) is cytotoxic;
      (ii) could need metabolization to present deleterious effects on
      cells;
      (iii) is capable of generating lesions in DNA and pathways as base
      excision repair, recombination and SOS system would be important to
      recover these lesions.
      PMID: 16804638


      This positive study also used the Comet assay to assess genotoxicity:

      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
      damaged.

      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




      " In this report, we have roughly estimated the influence of
      the mutagenicity of steviol, used as low calorie sweetener in
      our daily life, in comparison to that of AF2, which was previously
      used as an authorized food preservative. In the case of
      a cup of coffee, with the assumption of the common size of
      commercial individually packed sugar in Japan as ranging
      from three to five grams, the average amount of sugar can be
      assumed as four grams per cup. To provide similar sweetness,
      only 16 mg of stevia is necessary as the sugar substitute
      for the same cup of coffee. According to the specific mutagenic
      values of our experimental data, as shown in Table 1,
      only 0.6 mg stevia is necessary to indicate the similar
      strength in mutagenicity under the absence of S9 mixture as
      that given by 16 mg of stevia. Using values for AF2, whose
      levels were permitted up to 2 mg for preserving 100 g of fish
      sausage products from 1965 to 1974 in Japan, the mutagenic
      activity given by 2 mg of AF2 is calculated to be equivalent
      to 48 g of stevia, which translates to 3000 cups of coffee.

      >From this simulation, the genetic toxicity of stevia can be regarded
      as negligible and safe, as long as we limit its use in
      ordinary amount for our daily life. Although further studies,
      such as the effect of heating on the activity of stevia, or the
      metabolic fate of its lactone derivatives in our body are necessary,
      the present paper suggests that there are no serious
      genotoxic problem with the daily usage of this low-calorie
      sweetener. "

      Chem Pharm Bull (Tokyo). 2002 Jul; 50(7): 1007-10.
      Mutagenicity of steviol and its oxidative derivatives in
      Salmonella typhimurium TM677.

      * Terai T,
      * Ren H,
      * Mori G,
      * Yamaguchi Y,
      * Hayashi T.

      Department of Applied Chemistry, Osaka Institute of Technology,
      Japan. terai@...

      Stevioside is natural non-caloric sweetner isolated from Stevia
      rebaudiana BERTONI, which has been used as a non-caloric sugar
      substitute in Japan.

      Pezzuto et al. demonstrated that steviol shows a dose-dependent
      positive response in forward mutation assay using Salmonella
      typhimurium TM677 in the presence of metabolic activation system
      (Aroclor induced rat liver S9 fraction).

      Our studies were carried out to identify the genuine mutagenic active
      substance from among the eight steviol derivatives.

      Steviol indicate almost similar levels of mutagenicity under the
      presence of S9 mixture, as reported by Pezzuto et al.

      15-Oxo-steviol was found to be mutagenic at the one tenth the level of
      steviol itself under the presence of S9 mixture.

      Interestingly, specific mutagenicity of the lactone derivative under
      the presence of S9 mixture was ten times lower than that of the
      lactone derivative without the addition of S9 mixture.
      PMID: 12130868

      http://www.jstage.jst.go.jp/article/cpb/50/7/50_1007/_article/-char/en
      free full text
      http://www.jstage.jst.go.jp/article/cpb/50/7/1007/_pdf 68 KB

      Tadamasa Terai 1),
      Huifeng Ren 2),
      Go Mori 1),
      Yoshihito Yamaguchi 1) and
      Tetsuhito Hayashi 2)
      1) Department of Applied Chemistry, Osaka Institute of Technology
      5-16-1 Omiya, Asahi-ku, Osaka 535-8585, Japan: and
      2) Department of Food Science and Technology, Tokyo University of
      Fisheries
      4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan.
      (Received March 19, 2002) (Accepted May 7, 2002)

      References

      1) Wood H. B., Allerton R., Diehl H. W., Fletcher H. G., J. Org.
      Chem., 20, 875-883 (1955).

      2) Akashi H., Yokoyama Y., Shokuhinkougyo, 10, 34-43 (1975).

      3) Xili L., Chengjiany B., Eryi X., Fed. Chem. Toxicol., 30, 957-965
      (1992).

      4) Kato R., Gillette J. R., J. Pharmacol. Exp. Ther., 150, 285-291
      (1965).

      5) Wingard R. E., Jr., Brown J. P., Enderlin F. E., Dale J. A., Hale
      R. L., Seitz C. T., Experientia, 36, 519-520 (1980).

      6) Pezzuto J. M., Compadre C. M., Swanson S. M., Nanayakkara N. P. D.,
      Kinghorn A. D., Proc. Natl. Acad. Sci. U.S.A., 82, 2478-2482 (1985).

      7) Suttajit M., Vinitketkaumnuen U., Meevatee U., Buddhasukh D.,
      Environ. Health Perspect., 101, 53-56 (1993).

      8) Matsui M., Matsui K., Kawasaki Y., Oda Y., Noguchi T., Kitagawa Y.,
      Sawada M., Hayashi M., Nohmi T., Yoshihira K., Ishidate M., Jr.,
      Sofuni T., Mutagenesis, 11, 573-579 (1996).

      9) Yoshioka I., Saijoh S., Warers J. A., Kitagawa I., Chem. Pharm.
      Bull., 20, 2500-2502 (1972).

      10) Terai T., Nippon Nogeikagaku Kaishi, 63, 1119-1121 (1989).

      11) Skopek T., Liber H. L., Kaden D. A., Thilly W. G., Proc. Natl.
      Acad. Sci. U.S.A., 75, 4465-4469 (1978).

      12) Skopek T., Liber H. L., Krolewski J. J., Thilly W. G., Proc. Natl.
      Acad. Sci. U.S.A., 75, 410-414 (1978).

      13) Takagi Y., Goto S., Murata T., Matsushita H., Lewtas J., Taiki
      Osen Gakkaishi (J. Jpn. Soc. Air Pollution), 23, 24-31 (1988).

      14) Ren H., Hayashi T., Goto S., Ohkubo T., Endo H., Watanabe E.,
      Nippon Suisan Gakkaishi (J. Jpn. Soc. Fish. Sci.), 63, 90-96 (1997).



      http://groups.yahoo.com/group/aspartameNM/message/1201
      here's three more stevia abstracts: lowers blood pressure, Lee CN 2001
      Dec: antiviral, Takashashi K 2001 Jan: antihyperglycemic, Jeppesen
      PB,
      2000 Feb: Murray 2005.08.07

      Planta Med. 2001 Dec; 67(9): 796-9.
      Inhibitory effect of stevioside on calcium influx to produce
      antihypertension.
      Lee CN, Wong KL, Liu JC, Chen YJ, Cheng JT, Chan P.
      Department of Medicine, Taipei Medical University-Wan Fang Hospital,
      Wen Shan, Taipei, Taiwan.

      Antiviral Res. 2001 Jan; 49(1): 15-24.
      Analysis of anti-rotavirus activity of extract from Stevia rebaudiana.
      Takahashi K, Matsuda M, Ohashi K, Taniguchi K, Nakagomi O, Abe Y,
      Mori S, Sato N, Okutani K, Shigeta S.
      Department of Microbiology, School of Medicine, Fukushima Medical
      University, 1 Hikarigaoka, Fukushima-shi 960-1295, Japan.
      k-t...@...

      Metabolism. 2000 Feb; 49(2): 208-14.
      Stevioside acts directly on pancreatic beta cells to secrete insulin:
      actions independent of cyclic adenosine monophosphate and
      adenosine triphosphate-sensitive K+-channel activity.
      Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K.
      Department of Endocrinology and Metabolism, Aarhus University
      Hospital, Denmark.


      http://groups.yahoo.com/group/aspartameNM/message/1201
      here's three more stevia abstracts: lowers blood pressure, Lee CN 2001
      Dec: antiviral, Takashashi K 2001 Jan: antihyperglycemic, Jeppesen PB,
      2000 Feb: Murray 2005.08.07

      http://groups.yahoo.com/group/aspartameNM/message/1199
      yet three more stevia abstracts: mutagenic in bacteria, Terai T, 2002
      July: lowers blood pressure in rats, Hsu YH, 2002 Jan:
      antihyperglycaemic, insulinotropic and glucagonostatic benefits in
      rats,
      Jeppesen PB 2002 Jan; Murray 2005.08.07

      http://groups.yahoo.com/group/aspartameNM/message/1198
      three more stevia abstracts: no genotoxicity in mice, Sekihashi K,
      Saitoh H, Sasaki Y 2002 Dec: lowers blood pressure in dogs,
      Liu JC 2003 Jan: inhibits tumors in mice, Yasukawa K 2002 Nov:
      Murray 2005.08.05

      http://groups.yahoo.com/group/aspartameNM/message/1197
      three abstracts on expert stevia research: hypertension, Chan P
      2000 Sept; microflora, Gardana C 2003.10.22; helps blood pressure
      and glucose level, Jeppesen PB 2003 Mar: Murray 2005.08.05

      http://groups.yahoo.com/group/aspartameNM/message/1196
      Alan in alt.support.diabetes re Stevia and Glycemic and Hypertension
      Control
      2004.05.14: 2 year large scale blood pressure study, Hsieh MH, 2003
      Nov:
      insulin in muscles, Lailerd N 2004 Jan: glucose in diabetics,
      Gregersen S
      2004 Jan: Murray 2005.08.04

      http://groups.yahoo.com/group/aspartameNM/message/1179
      Stevia (stevioside) is safe: Prof. Jan M.C. Geuns: Murray 2005.07.06

      http://groups.yahoo.com/group/aspartameNM/message/1084
      26 stevia safety abstracts since 1993: aspartame vs stevia debate on
      alt.support.diabetes, George Schmidt, OD: Murray 2004.05.25 rmforall
      ///////////////////////////////////////////////////////////


      aspartame (methanol, formaldehyde) toxicity research summary: Rich
      Murray 2007.05.03
      http://groups.yahoo.com/group/aspartameNM/message/1404

      One liter aspartame diet soda, about 3 12-oz cans,
      gives 61.5 mg methanol,
      so if 30% is turned into formaldehyde, the formaldehyde
      dose of 18.5 mg is 37 times the recent EPA limit of
      0.5 mg per liter daily drinking water for a 10-kg child:
      www.epa.gov/teach/chem_summ/Formaldehyde_summary.pdf
      2007.01.05 [ does not discuss formaldehyde from methanol
      or aspartame ]
      http://www.epa.gov/teach/teachsurvey.html comments
      teach@...


      "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 74 members, 1,419 posts in a public, searchable archive
      http://RMForAll.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://groups.yahoo.com/group/aspartameNM/message/1395
      Aspartame Controversy, in Wikipedia democratic
      encyclopedia, 72 references (including AspartameNM # 864
      and 1173 by Murray), brief fair summary of much more
      research: Murray 2007.01.01


      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.
      ///////////////////////////////////////////////////////////
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