View Full Version : stevia to be approved and cyclamates limited by Food Standards Australia New Zealand

06-05-2007, 01:21 AM
stevia to be approved and cyclamates limited by Food Standards Australia New Zealand: JMC Geuns critiques of two recent stevia studies by Nunes: Murray 2007.05.29


FSANZ mulls changes to food laws

Food Standards Australia New Zealand (FSANZ) today invited comment
on proposed changes to the Australia New Zealand Food Standards Code –
regulations that apply to all food sold in Australia and New Zealand.

Among the changes being contemplated are the deletion of two antibiotics from the Code,
the use of steviol glycosides and cyclamates as sugar substitutes,
a genetically modified corn variety and a food additive for wine.

FSANZ is inviting comment from the general public, the food industry, health
professionals and government agencies on the proposed changes to the Code.
FSANZ summarises all submissions in a final report and explains what action, if
any, it has taken in response to issues raised in submissions.

Steviol glycosides as intense sweeteners (Application A540 – Draft Assessment)

The Plant Sciences Group of Central Queensland University and Australian Stevia Mills Pty Ltd have applied for the Code to be amended to allow the use of steviol glycosides as an intense sweetener for a wide variety of foods.
Steviol glycosides extracted from the herbStevia rebaudianaare 250-300 times sweeter than sucrose.
We have estimated the dietary exposure of consumers at the maximum levels
proposed by the applicant and have concluded that there are no public health and safety concerns.
Comment is invited.

Review of cyclamate permissions (Proposal P287 – Draft Assessment)

A FSANZ-commissioned survey in 2004 on the consumption of intense sweeteners in Australia and New Zealand concluded that the estimated dietary exposure of some consumers of cyclamate products for retail sale exceeded the acceptable daily intake (ADI) for cyclamate.
The major contributors to estimated dietary cylcamate exposures were water-based flavoured drinks (eg. soft drinks, cordials).
We are therefore intending to reduce the maximum permitted level for cyclamates in water-based flavoured drinks and to allow the use of cyclamates in tabletop sweeteners.
We believe these measures will protect the public health and safety of
We invite comment from all interested parties.

Submissions: FSANZ welcomes public comment from industry, public health
professionals, government agencies and consumers.
Details of all the assessments above can be found on Food Standards Australia New Zealand .
Submissions close on 4 July 2007 .

Media contact: Lydia Buchtmann 0401 714 265 (Australia) or +61 401 714 265 (from New Zealand)

[ See later in this post for extracts from 89page review. ]

Food Standards Australia New Zealand

Food Standards Australia New Zealand FSANZ

Boeing House 55 Blackall Street BARTON ACT 2600
Ph: +61 2 6271 2222 Fax: +61 2 6271 2278
Reception: reception@foodstandards.gov.au
PO Box 7186 Canberra BC ACT 2610 Australia

Information/Publications Officer: info@foodstandards.gov.au
For: Copies of publications, fact sheets and brochures;
Website enquiries;
Consumer enquiries.

Standards Management Officer: slo@foodstandards.gov.au
for: making an application;
progress with the assessment of applications or proposals or completed
making submissions on applications and proposals which have been released for public comment;
Gazettal of amendments to the Code.

New Zealand:
Level 6 108 The Terrace WELLINGTON NEW ZEALAND
Ph: +64 4 473 9942 Fax: +64 4 473 9855
PO Box 10559 The Terrace, Wellington 6036 New Zealand
email: info@foodstandards.govt.nz


Application A540 - Stevol Glycosides as Intense Sweeteners

Draft Assessment Report - 23 May 2007 [ word | pdf 584 kb ]

Inital / Draft Assessment Report 7 December 2005 [ word | pdf 187 kb ]

http://www.foodstandards.gov.au/_src..._DAR_FINAL.pdf 89

pag1 3-07
23 May 2007
DEADLINE FOR PUBLIC SUBMISSIONS: 6pm (Canberra time) 4 July 2007
(See ‘Invitation for Public Submissions’ for details)
For Information on matters relating to this Assessment Report or the assessment process generally, please refer to Food Standards Australia New Zealand: Standards Development

06-05-2007, 01:27 AM
[ Continued ]


Application A540 - Stevol Glycosides as Intense Sweeteners

Draft Assessment Report - 23 May 2007 [ word | pdf 584 kb ]

Inital / Draft Assessment Report 7 December 2005 [ word | pdf 187 kb ]

http://www.foodstandards.gov.au/_srcfiles/A540_Stevioside_DAR_FINAL.pdf 89 pages

pag1 3-07
23 May 2007
DEADLINE FOR PUBLIC SUBMISSIONS: 6pm (Canberra time) 4 July 2007
(See ‘Invitation for Public Submissions’ for details)
For Information on matters relating to this Assessment Report or the assessment process generally, please refer to Food Standards Australia New Zealand: Standards Development (http://www.foodstandards.gov.au/standardsdevelopment/)

pages 87-89 Attachment 5

Summary of Submissions

Initial Assessment

Sixteen submissions were received in response to the Initial Assessment Report.

Fourteen submissions supported the progression of the Application to Draft
Assessment with industry submissions strongly supporting the approval of steviol glycosides as an intense sweetener.

Two submissions suggested deferring the Draft Assessment until after JECFA had evaluated the additional studies requested at its 63rd meeting.

Submitter Comments

Complementary Healthcare Council (CHC)
The CHC has no concerns with the progression of this application.

Department of Human Services Victoria (DHS)
DHS notes steviol glycosides are not permitted for use in the EU
or USA, however, are approved and used in other countries.
DHS will provide further comment at the Draft Assessment stage
after reviewing the toxicological and dietary modelling data.

Crop & Food Research New Zealand
Crop & Food Research New Zealand support A540 based on
Initial Assessment.
It is noted that safety literature has not been examined
by Crop and Food Research.

DIC International (Australia) Pty. Ltd.
DIC International strongly supports A540.
DIC International also provided additional information including:
• history and manufacturing process of stevia;
• merits and defects of stevia as a sweetener;
• metabolism of stevia;
• some additional Toxicological information; and
• countries where stevia is approved for use.

Fonterra Brands Australia (P& B)
Fonterra Brands Australia (P & B) supports progression of A540
to Draft Assessment.
Additional Comments:
• Steviol glycosides would provide alternative intense sweeteners
for use.
• Consumer research shows interest in low caloric foods.
• Suggest FSANZ may consider why this additive is not permitted
for use in the US or Europe.

SA Department of Health SA Department of Health
has no objections to the progression of this application.


Submitter Comments
New Zealand Food Safety Authority (NZFSA)
NZFSA supports A540 proceeding to Draft Assessment.
Additional comments to consider in the Draft Assessment include:
• only a temporary ADI has been set with JECFA waiting for
further data (does this application contain the extra information
requested by JECFA?);
• consideration needs to be given to JECFA concerns regarding
pharmacological effects particularly in relation to Type I & II diabetics;
• NZFSA believe dietary modelling needs to consider exposure
from table top sweeteners;
• NZFSA is aware of a dietary supplement sold in NZ as ‘Stevia
Dietary Supplement’ which contains 60 mg Stevia rebaudiana
Bertoni extract per 1g serving; and
• NZFSA suggests clarification be sough re: status of
stevia from the Novel Foods Reference Group.

New Zealand Juice & Beverage Association Inc (NZJBA)
NZJBA support A540. NZJBA believe that this will extend the
number of approved sweeteners available increasing consumer choice.

Australian Beverages Council Ltd (ABCL)
ABCL supports approval of steviol glycosides as a food additive.
Additional comments:
• Temporary JECFA ADI is based on a 200-fold safety factor
assuming a mid-dose of 970 mg/kg of stevioside was the NOEL
in rat carcinogenicity study. ABCL and the University of
Queensland believe it to based on a NOEL of 2,000 mg/kg.
Believe the ADI can safely be assessed at 4 times that set by JECFA
• ABCL requests FSANZ approves a use level of steviol
glycosides at 1000 ppm in water based flavoured beverages and
fruit and vegetable juice products. ABC note that milk and soy
containing beverages will require more stevia sweeteners
because of their protein and fat contents and request amount
permitted to be 1000 ppm.
• ABCL suggests dietary modelling should be conservative in
assumptions of market use. They suggest dietary modelling
should be based on current uses of aspartame and other
approved sweeteners are appropriate.
• ABCL believes that JECFA’s assessment of steviol glycosides
replacing 20-30% of sugar is very optimistic market assessment.
• ABCL believe there will be consumer benefit through controlled
energy intake while enjoying food and beverages.
• ABCL also notes the potential development of a new
agricultural crop for Australia.


Submitter Comments

Australian Stevia Mills Supports application A540.
Additional comments
• Stevia is a safe natural alternative to artificial sweeteners
• Stevia does not promote calories
• Stevia is safe to use in baked products and products with varying pH.
• Currently no artificial sweeteners are locally owned products,
potential cash crop for Australia.
Successful trials in Eastern states of Australia.
• The federal government supports development of stevia through
projects under RIRDC.
• Potential stakeholder benefits to federal and state governments,
diabetic and obese people, general public in reducing dental caries

Australian Food and Grocery Council (AFGC)
Supports A540 – Steviol glycoside as an intense sweetener.

Health & Herbs Ltd Supports A540 – Steviol glycoside as a sweetener

Queensland Health -Environmental Health Unit
Believe FSANZ should defer further assessment until 2007 when
additional studies on pharmacological effects of the sweetener
(required by FAO/WHO).
Suggest delay will not be significant to industry as other intense sweeteners
are available.
Also notes that EU and USA do not currently permit steviol glycosides.

Cadbury Schweppes
Supports A540 – Steviol glycosides as a sweetener in a broad
range of products

NSW Food Authority
Recommends waiting for further toxicological data required by JECFA.
Notes that the NFRG formed the view that stevia is a novel food,
therefore the novelty of this food will need to be assessed

Food Technology Association of Victoria Inc
Supports A540 – Steviol glycosides as a sweetener

page 33 Conclusions

This review of supplementary data indicated that stevioside is metabolised
completely to steviol in the gastrointestinal tract, which is absorbed into the blood stream and then exerts a pharmacological effect by lowering blood pressure and blood glucose. While the precise mechanism of pharmacological action remains to be defined, stevioside is unlikely to produce
hypoglycaemia or hypotension in humans at concentrations encountered in the diet. Studies previously reviewed by JECFA confirm the low toxicity potential of stevioside.
On this basis, there are unlikely to be any safety issues associated with the use of stevioside as a sweetener.
No suitable human study was identified that could serve as a basis of an ADI for stevioside.
However, steviol glycosides are well tolerated and unlikely to have adverse
effects on blood pressure, blood glucose or other parameters in normal, hypotensive or diabetic subjects at doses up to 11 mg/kg bw/day.

The adequacy of the existing database and a new study in humans provides a basis for revising the uncertainty factors that were used by JECFA to derive the temporary ADI for steviol glycosides in 2005.
In particular, the evidence surrounding the pharmacological effects of steviol glycosides on blood pressure and blood glucose has been strengthened so
that the additional 2-fold safety factor for uncertainty related to effects in
normotensive or diabetic individuals is no longer required.

As the ADME data indicated that stevioside is completely converted to steviol in animals and humans, the ADI is expressed in terms of steviol equivalents. This allows for any variability in the individual glycosides in mixtures of steviol glycoside extracts (e.g. different ratios of stevioside/rebaudioside) to be accounted for by the ADI being expressed in steviol equivalents.
Therefore, based on this complete metabolism, a conversion factor of 40% from the steviol glycoside, stevioside (relative molecular mass: stevioside, 805; steviol, 318) to steviol is used to calculate the ADI.

Therefore a full ADI of 4 mg/kg bw/day, derived by applying a 100-fold safety
factor to the NOEL of 970 mg/kg bw/day (equivalent to 383 mg/kg bw/day steviol) in a 2-year rat study, has been established.
At the next highest dose equivalent to 2000 and 2400 mg/kg bw/day in males and female rats, respectively reduced bodyweight gain and survival were

06-05-2007, 01:29 AM
[ Continued ]


Abudula R, Jeppesen PB, Rolfsen SED et al (2006)
Rebaudioside A potently stimulates secretion
from isolated mouse islets: studies on the dose, glucose and calcium-dependency.
Metabolism, 53, 1378-1381.

Barriocanal LA, Palacios M, Benitez G et al (2006)
Lack of pharmacological effect of steviol
glycosides as a sweetener in humans.
Studies on repeated exposures in normotensive and hypotensive
individuals and Type 1 and Type 2 diabetes. Unpublished report.

Bopp and Price P (2001) Cyclamate:
In: O-Brien Nabors L. eds. Alternative Sweeteners: Third
Edition revised and Expanded. Chapter 5.
Marcel Dekker Inc, New York, pp 63-85.

Chan P, Tomlinson B, Chen YJ et al (2000)
A double-blind placebo-controlled study of the
effectiveness and tolerability of oral stevioside in human hypertension.
Br J Clin Pharmacol, 50, 215-20.

Chen TH, Chen SC, Chan P et al (2005)
Mechanism of the hypoglycaemic effect of stevioside a
glycoside of Stevia rebaudiana.
Planta Med., 71, 108-113

Chen J, Jeppesen PB, Abudula R et al (2006)
Stevioside does not cause increased basal insulin
secretion or -cell desensitisation as does sulphonylurea, glibenclamide:
studies in vit ro
Life Sciences, 78, 1748-1753.

Ferri LAF, Alves-Do-prado W, Yamada SS et al (2006)
Investigation of the anti-hypertensive effect
of oral crude stevioside in patients with mild hypertension.
Phytotherapy Research, 20, 732-736.

Ferreira EB, Neves F, Da Costa MAD (2006)
Comparative effects of Stevia rebaudiana leaves and
stevioside on glycaemia and hepatic gluconeogenesis.
Planta Med., 72, 691-696.

Gardana C, Simonetti P, Canzi E et al (2003)
Metabolism of stevioside and rebaudioside A from
stevia rebaudiana extracts by human microflora.
J Agric Food Chem, 51, 6618-6622.

Geuns JMC, Augustijns P, Mols R et al (2003)
Metabolism of stevioside in pigs and intestinal
absorption characteristics of stevioside, rebaudioside A and steviol.
Food. Chem. Toxicol., 41, 1599-1607.

Geuns JMC (2004)
Review: The safety of stevioside used as a sweetener.
Proceedings of the first symposium on the safety of stevioside.
Kuleuven, 16 April 2004. Chapter 9, pp. 85-127.

Geuns JMC and Pietta P (2004)
Stevioside metabolism by human volunteers (unpublished report).
Laboratory Functional Biology, Kuleuven, Kasteelpark Arenberg. Belgium.

Geuns, J.M., Buyse, J., Vankeirsbilck, A., Temme, E.H., Compernolle, F., Toppet,
S. (2006a).
Identification of steviol glucuronide in human urine.
J Agric Food Chem, 5, 2794-2798.

Geuns JMC, Buyse J, Vankeirsbilck A et al (2006b)
Metabolism of stevioside in healthy subjects.
Unpublished report.
Laboratory Functional Biology, Kuleuven, Kasteelpark Arenberg. Belgium.

Goto A and Clemente E (1998)
Influence of rebaudioside on the solubility and flavour of stevioisde.
Food Science and Technology, v18, Jan/April edition.

Gregersen S, Jepperson PB, Holst JJ and Hermansen K (2004)
Antihyperglycemic effects of stevioside in type 2 diabetic subjects.
Metabolism, 53, 73-76.

Hanson JR and Oliveira BH (1993)
Stevioside and related sweet diterpenoid glycosides.
Nat. Prod. Rep, 10, 301-309.

Hong J, Chen L, Jeppesen PB (2006)
Stevioside counteracts the -cell hypersecretion caused by longterm
palmitate exposure.
Am J Physiol Endocrin Metab, 290, E416-E422.

Hsieh MH, Chan P, Yuh-Mou S et al (2003)
Efficacy and tolerability of oral stevioside in patients
with mild essential hypertension: a two-year, randomized, placebo-controlled
Therapeutics, 25, 2797-2808. Abstract only.

Hutapea AM, Toskulkao C, Buddhasukh D et al (1997)
Digestion of stevioside, a natural sweetener,
by various digestive enzymes.
J. Clin. Biochem. Nutr. 23, 177-186.

Hutapea AM, Toskulkao C, Wilairat P and Buddhasukh D (1999)
High-performance liquid chromatographic separation
and quantification of stevioside and its metabolites.
J. Liq. Chrom. & Rel. Technol, 22, 1161-1170.

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

Jeppesen PB, Gregersen S, Alstrup KK and Hermansen K (2002)
Stevioside induces
antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo:
studies in the diabetic Goto-Kakizaki (GK) rats.
Phytomedicine, 9, 9-14.

Jeppesen PB, Gregersen S, Alstrup KK and Hermansen K (2003)

Antihyperglycemic and blood pressure-reducing effects of stevioside
in the diabetic Goto-Kakizaki rat.
Metabolism Clinical & Experimental, 53, 372-378.

Koyama E, Sakai N, Ohori Y et al (2003a)
Absorption and metabolism of glycosidic sweeteners of stevia mixture
and their aglyocne, steviol, in rats and humans.
Food. Chem. Toxicol., 41, 875-883.

Koyama E, Kitazawa Y, Ohori O et al (2003b)
In vitro metabolism of the glycosidic sweeteners,
stevia mixture and enzymatically modified stevia in human intestinal microflora.
Food. Chem. Toxicol., 41, 359-374.

Lailerd N, Saengsirisuwan V, Sloniger JA et al (2004)
Effects of stevioside on glucose transport activity
in insulin-sensitive and insulin-resistant rat skeletal muscle.
Metabolism Clinical & Experimental, 53, 101-107.

Lee CN, Wong KL, Liu JC (2001)
Inhibitory effect of stevioside on calcium influx to produce antihypertension.
Planta Medica, 67, 796-799

Liu JC, Kao PK, Chan P et al (2003)
Mechanism of the antihypertensive effect of stevioside in anaesthetised dogs.
Pharmacology (Basel), 67, 14-20

Melis MS (1996)
A crude extract of Stevia rebaudiana increases the renal plasma flow of normal
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Brazilian J Med Biol Res, 29, 669-675

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Alternative Sweeteners,
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J. Food Hyg. Soc. Jpn., 27, 1-8.

Simonetti P, Gardana C, Bramati L and Pietta PG (2004)
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Proceedings of the first symposium on the safety of stevioside.
Kuleuvan. Euprint Editions ISBN.

Starratt AN, Kirby CW, Pocs R and Brandle JE (2002)
Rebaudioside F, a diterpene glycoside from Stevia rebaudiana.
Phytochemistry, 59, 367-370.

Sung LH (2002)
Report on the pharmacokinetic studies of T100 Sunstevia 95% stevioside in rats.
Sunlabel Pty Ltd, 21 Marsiling Industrial Estate, Road 9, Singapore 739175.
Unpublished report.

Temme EH, Vankeirsblick A and Buyse J.
A short term study of stevioside in healthy subjects.
Proceedings of the first symposium on the safety of stevioside.
Kuleuven, 16 April 2004. Chapter 7, p 63 -74.

Totté, N., Charon,L., Rohmer, M., Compernolle, F., Baboeuf, I., Geuns, J.M.C.,
Biosynthesis of the diterpenoid steviol, an ent-kaurene derivative
from Stevia rebaudiana Bertoni,
via the methylerythritol phosphate pathway.
Tetrahedron Letters 41, 6407-6410.

Wang LZ, Goh BC, Fan L and Lee HS (2004)
Sensitive high-performance liquid chromatography/mass spectrometry method
for determination of steviol in rat plasma.
Rapid. Commun. Mass. Spectrom., 18, 83086.

WHO (1999)
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Food Additives Series No. 42, WHO, Geneva.

WHO (2005)
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(steviol glucosides). WHO Technical Report Series No. 928, WHO, Geneva.

Wingard RE, Brown JP, Enerlin FE et al (1980)
Intestinal degradation and absorption of the glycosidic sweeteners stevioside
and rebaudioside A.
Experientia, 36, 519-520.

Wong KL, Lin JW, Liu JC (2006)
Antiproliferative effect of isosteviol on angiotension-II-treated rat
aortic smooth muscle cells.
Pharmacology, 76, 163-169.

Yahoo! Groups (http://groups.yahoo.com/group/aspartameNM/message/1436)
FDA's corrupt war against safe herbal sweetener stevia,
Mary Nash Stoddard, 2006 January,
Aspartame Consumer Safety Network: Murray 2007.05.24

[ See also:

stevia, balanced factual detailed review in Wikipedia: Murray
Yahoo! Groups (http://groups.yahoo.com/group/aspartameNM/message/1430)
Stevia - Wikipedia, the free encyclopedia (http://en.wikipedia.org/wiki/Stevia)

Yahoo! Groups (http://groups.yahoo.com/group/aspartameNM/message/1419)
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

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. ]