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 2004.05.17

[ the EU report:
http://www.foodstandards.gov.uk/multimedia/webpage/stevia

Herein, I copy in plain text the full text of 26 PubMed abstracts since
1994, all of the stevia studies that in some way studied safety and
beneficial effects-- they are overwhelmingly positive for diabetes
treatment, blood pressure reduction, and even antibiotic effects, with
little evidence for genotoxicity, and in one study, reduction in fertility
in male rats (Melis, 1999).

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


From: Dr. George Schmidt (doc@(REMOVE)i-care.net)
Subject: Re: Splenda or Stevia ? Pubmed Studies
Newsgroups: alt.support.diabetes
Date: 2004-05-11 09:35:45 PST

"Iowa883" <dswebber@...> wrote in message
news:c7p2a7$ivl$1@....
> Are these good substitutes for diabetics ? Type 2 ? Do they make any
> difference on Blood sugar readings ?
> Thanks, Iowa883

Actually, a few studies have shown a benefit to Type 2 Diabetics from stevia
consumption, as well as lowering blood pressure:

There is no good reason that stevia is not permitted to be sold in the USA
as a sweetener, other than politics (the artificial sweetener and sugar
industries have powerful lobbyists). Stevia is commonly used in Europe,
where you can't even buy moderate dose vitamin C without a prescription.

Studies have confirmed stevia's safety:

Splenda and aspartame may be safe, but no studies have shown a beneficial
effect for diabetics, other than from reducing sugar/caloric consumption.
Stevia comes in different forms, one of which is a thick molasses-like
liquid, which tastes horrible. The powdered form tastes best.

George L. Schmidt, O.D.
http://www.i-care.net


From: Dr. George Schmidt (doc@(REMOVE)i-care.net)
Subject: Studies Question Safety of Aspartame (NutraSweet)
Newsgroups: alt.support.diabetes
Date: 2004-05-14 10:43:12 PST

At the risk of irritating some members of this group (you know who you are),
I present this information for the education of the open-minded majority,
others please ignore:

While Pubmed has few studies posted showing any adverse effects of Aspartame
(aka NutraSweet®, Equal®), the studies that confirm its safety are mostly
sponsored by the companies which profit from its sale, creating a
significant conflict of interest. Of 166 studies felt to have relevance for
questions of human safety, 74 had Nutrasweet® industry related funding and
92 were independently funded. One hundred percent of the industry funded
research attested to aspartame's safety, whereas 92% of the independently
funded research identified a problem. The studies that were NOT industry
sponsored is at:
http://www.dorway.com/nonindus.html

More references on safety issues are at:
http://www.dorway.com/peerrefs.html

The number of studies, especially during the investigation-phase of this
product, which showed adverse effects certainly makes Stevia look like a
much safer alternative, especially for diabetics who might benefit from its
BG lowering effects. The key is to be consistent in its use and monitor
your sugar carefully. Try different brands of stevia before giving up on
it, as some are nasty tasting. It's also much sweeter than Equal®, so use
significantly less than you might think is necessary.

George L. Schmidt, O.D.


From: Dr. George Schmidt (doc@(REMOVE)i-care.net)
Subject: STEVIA is SAFE and BENEFICIAL - Studies Prove it:
Newsgroups: alt.support.diabetes
Date: 2004-05-14 20:39:09 PST

For the record, I had never heard of Betty Martini previous to my earlier
thread and just noticed references to her at http://dorway.com. I have only
recently become interested in the relative differences between stevia and
aspartame after reading this newsgroup last week and have learned much from
my researching the two. I do not sell stevia, although I've taken it in my
coffee each morning for a couple of years.

Regarding STEVIA: After reading the link that "Old Al" provided in a
previous thread http://www.foodstandards.gov.uk/multimedia/webpage/stevia
(and the link within that link), the whole gist of the European non-approval
was not that Stevia is hazardous, but rather that there were not adequate
safety studies. The few negative studies of stevioside were found in rats
at extremely high doses, and included male infertility (not a problem for
me, I've already got my four kids!). This and the other cytotoxicity
concerns have all since been disproven (see Pubmed references below).

The reason there weren't many studies showing safety has only to do with the
lack of patent protection (hence, funding) for the studies and the fact that
it's been used for centuries safely in South America with no ill effects
(wouldn't you think that it would be banned there if it were toxic?). If
you don't think politics played a role in the banning of stevia in the EU as
well as the USA, you don't understand how corporate power and money can
corrupt. Another reason, I'm sure is that stevia lowers blood glucose, a
well documented side effect and medicinal use. The EU (and USA)
pharmaceutical companies do not like any natural substance which might
decrease sales of their patent drugs. You cannot even buy 100mg vitamin C
tablets in the EU, which shows how restrictive their laws are!

More recently, many good toxicity studies have been done, none of which were
industry sponsored (except maybe by the NutraSweet people, who would have
hoped for different results) making them all the more believeable. To read
the abstracts go to http://www.Pubmed.com and use the search terms: "stevia
toxicity". Interestingly NOT ONE NEGATIVE STUDY SHOWS UP WITH THIS SEARCH,
even at levels a hundred times higher than one would normally consume!

That's in spite of the fact that these studies were likely done because the
researchers very likely expected to find significant toxicity (negative
results are not very newsworthy).

On the POSITIVE SIDE OF STEVIA, go to http://www.pubmed.com and do a search
on "stevia blood glucose". EVERY abstract shows that stevia improved
insulin sensitivity, improved pancreatic insulin output and benefitted Type
II Diabetics! These are both human and animal studies. Of course, it's not
a cure, and one should always consult their physician, carefully monitor
their BG levels and be consistent in their stevia consumption every day.
(The pharmaceutical companies don't want you to reduce your medications, so
they won't approve of this.) It's too bad that aspartame doesn't have the
positive independent studies that stevia has!

Those who say stevia is toxic are totally ignorant of the facts, and
unwilling to change their thinking, even when it's wrong. They are spouting
what the artificial sweetener people want you to believe, and are blind to
the facts. Are they big enough to admit it? I doubt it.

Anybody who has actually LOOKED AT the studies above may reply to this post,
but if you just want to spout more rosenbergisms, please don't show your
ignorance and lack of interest in sharing the truth! Focus on the facts,
and avoid personal attacks. (I'm a poet, and don't know it!)

George L. Schmidt, O.D.
http://www.i-care.net


From: Baerana (usenet1@...)
Subject: Re: STEVIA is SAFE and BENEFICIAL - Studies Prove it:
Newsgroups: alt.support.diabetes
Date: 2004-05-15 03:51:30 PST

> Those who say stevia is toxic are totally ignorant of the facts, and
> unwilling to change their thinking, even when it's wrong. They are
spouting
> what the artificial sweetener people want you to believe, and are blind to
> the facts. Are they big enough to admit it? I doubt it.
> Anybody who has actually LOOKED AT the studies above may reply to this >
post, but if you just want to spout more rosenbergisms, please don't show
> your ignorance and lack of interest in sharing the truth! Focus on the
> facts, and avoid personal attacks. (I'm a poet, and don't know it!)

I agree with you 1000%. At first I was wary of Stevia as I am wary of
all things before I research them, and when I started looking into
Stevia I did find several hysterical websites calling it poison (you can
find sites like that on just about any artificial sweetener, drug, food,
etc. you want). However, looking deeper, I find the real story - it
can't be patented thus the sugar and artificial sweetener companies are
in a rage about it. It's "unfair competition" because, since it can't
be patented and thus one company can't hold an artificial monopoly on it
it can be sold cheaply and they can't keep ripping off their customers
if it comes into widespread use here (in the U.S.). Well, tough - this
isn't a communist country and you aren't entitled to your "fair share"
of customers just because. If you can't compete, you die and that's
just the way capitalism works.

All the *real* studies I've read show Stevia as perfectly safe and
tasty. It makes up 40% of the sweetener market in Japan and everyone is
always raving about how healthy people in Japan are. It's also sold
extensively in South America.

The FDA "banned" it because, since it wasn't patentable, there were no
huge companies willing to give them millions to study it. The FDA has
now approved it as a supplement, so that should assure everyone it's
safe to consume. Aspartame and other artificial sweeteners taste like
crap to me - I'm very sensitive to them and can't consume anything with
the slightest amount of either. So far, Splenda and Stevia are the only
ones I can stand.

Anyway, I bought a box of Stevia yesterday. If I suddenly stop posting,
I guess you can assume it killed me :)


From: Dr. George Schmidt (doc@(REMOVE)i-care.net)
Subject: Re: STEVIA is SAFE and BENEFICIAL - Studies Prove it:
Newsgroups: alt.support.diabetes
Date: 2004-05-15 15:58:01 PST

"Truthfulness is the foundation for all human virtues." I don't lie, unlike
you, Ted and Mack. What has that got to do with anything, anyway? I'm
beginning to believe that you two are shills for the aspartame industry.
That's a common tactic, accusing others of doing what you do, to take the
focus off of you. You say Stevia is poison. Show us the studies, please.
Personal attacks just show your ignorance and your lack of decorum.

Your diatribes (look it up, Ted) cause much more harm to this newsgroup than
help. Newbies who come here asking legitimate questions are accused wrongly
of being <snips>. Who would want to return after that kind of abuse? If
you backed up your statements with facts, it might be excusable, but in the
short time I've been here, none of them have been factual.


From: Dr. George Schmidt (doc@(REMOVE)i-care.net)Subject: Re: STEVIA is SAFE
and BENEFICIAL - Studies Prove it:
Newsgroups: alt.support.diabetes
Date: 2004-05-16 15:01:06 PST

"J.C. Hartmann" <jch@...> wrote in message
news:2go1tlF4v3ngU1@....
<snip>
> Gee, George, you appear on ASD touting the dangers of Aspartame and
> pushing Stevia. You aren't diabetic, so you must have an agenda. What
> could that agenda be?
>
> Could it be the same one you have used over the past few years spamming
> various health oriented NGs with your supplement business? Google seems
> to show that you like to try to pass off "alternative" crap on sick
> people. Oh, and sell e-mail spamming services.

Again, if you can't fight the facts of the stevia debate, you attack the
messenger! None of you anti-steviaites has made one argument backing your
original claim, that stevia was dangerous. Regarding your post, however, I
will respond to your questions and statements:

1. My agenda is to educate the public about recent research which can
prevent and reduce eye and health problems. Regarding aspartame,
I'm concerned about my patients because methanol (aspartame is 11% methanol)
is a well documented macular toxin, and the recent increase in macular
disease is alarming retinal specialists. Diabetics are more prone to
macular degeneration than the general public. Could Nutrasweet be a
contributing cause? I don't know for sure, but I'm sure that stevia isn't
responsible (which I don't sell, so there goes that "agenda", although maybe
I should begin doing so since it appears to be so helpful for diabetics.)

2. I was experimenting with various online businesses 6-8 years ago, before
I knew better, but have not done so since 1998. You are talking ancient
history for the internet here, Pal, I was still using a text based browser
in those days!

3. Other than participating as a panelist on the internationally acclaimed
"Ask the Doctors" website/newsgroup, I have rarely posted on any newsgroups
since 1998.

> And then, despite you claiming you have never heard of Betty Martini or
> Nancy Markle, you manage to include her main scam site. Then, along
> comes her #1 buttboy, Little Richie Murray, to lend a hand.
<snip> Jim

I came across the http://www.dorway.com website recently while investigating
both sides of the aspartame argument. I have never contacted Martini or
Markle or even knew who they were (I only looked at the studies, not caring
who put the website up). I recently emailed Murray to ask where studies are
that show that there is any danger to humans from consuming aspartame, as I
found very few on Pubmed. Which studies that he posted earlier do you have
an issue with? He has read the entire studies thoroughly, something that I
don't have time to do and has come to a conclusion based on the results.
What he documents about Nutrasweet makes sense. (I doubt he owns stock in a
stevia growing business, so there's no financial motive for him, or anyone
else for that matter, to knock Nutrasweet.)


From: Alan (loralweightandcarbs@...)
Subject: Stevia and Glycemic and Hypertension Control
Newsgroups: alt.support.diabetes
Date: 2004-05-14 15:23:39 PST

Hullo All.

It appears that many people did not see this the first time round, and
it got "lost" in the expected argument on supplements etc.

But in the various arguments on Stevia, it's safety, or danger of
side-effects, and use as a sweetener, it seems to have been missed that
there are other implications apart from sweetness as a sugar substitute.

I should preface what follows by saying that I started investigating
this knowing nothing about Stevia other than the statements, some quite
strongly negative, made by posters on this group and m.h.d. So I was
expecting to find negative reports on the safety of stevia.

I had no real interest in the product, have never used it, and would not
know where to buy it. But, with a little time on my hands I decided to
do a little research.

I still found no info on medscape, and little on druginfo. But get ready
for a surprise, below is what I found on medline.
The studies may be devalued by some because some are on small groups,
some are on rats, none are in the US.

But they were all recent, well after the FDA and EU decisions, and they
were all positive.

And the most surprising thing for me was not just that they imply or say
stevia is safe, but that they imply that it may be a future drug for
type 2 diabetes management. I have only selected some of the reports,
and I have only searched medscape and medline with the term:
"stevia rebaudiana bertoni". I won't be doing any more research at this
stage, but it is certainly food for thought. You may wish to extend this
start if you have an interest.

I will at least have an open mind on this product for the future.

I have used selective snipping for brevity.

Small study in Denmark on "Twelve type 2 diabetic patients were included
in an acute, paired cross-over study."

Stevioside acts directly on pancreatic beta cells to secrete insulin:
actions independent of cyclic adenosine monophosphate and adenosine
triphosphate-sensitive K+-channel activity.

"In conclusion, stevioside and steviol stimulate insulin secretion via a
direct action on beta cells. The results indicate that the compounds may
have a potential role as antihyperglycemic agents in the treatment of
type 2 diabetes mellitus."

Geuns JM
Laboratory of Plant Physiology, Catholic University of Leuven,
Kasteelpark Arenberg 31, B 3001 Leuven, Belgium

"The conclusion is that Stevia and stevioside are safe when used as a
sweetener. It is suited for both diabetics, and PKU patients, as well as
for obese persons intending to lose weight by avoiding sugar supplements
in the diet. No allergic reactions to it seem to exist."

Phytomedicine 2002 Jan; 9(1): 9-14 (ISSN: 0944-7113)
Study in Denmark on rats.

"In conclusion, stevioside exerts antihyperglycaemic, insulinotropic,
and glucagonostatic actions in the type 2 diabetic GK rat, and may have
the potential of becoming a new antidiabetic drug for use in type 2
diabetes."

Clin Ther 2003 Nov; 25(11): 2797-808 (ISSN: 0149-2918)
This study was undertaken to investigate the long-term (2-year) efficacy
and tolerability of stevioside in patients with mild essential
hypertension.

This was a multicenter, randomized, double-blind, placebo-controlled
trial in Chinese men and women aged between 20 and 75 years with mild
essential hypertension (systolic blood pressure [SBP] 140-159 mm Hg and
diastolic blood pressure [DBP] 90-99 mm Hg). Patients took capsules
containing 500 mg stevioside powder or placebo 3 times daily for 2 years

"after 2 years, 6 of 52 patients (11.5%) in the stevioside group had
left ventricular hypertrophy (LVH), compared with 17 of 50 patients
(34.0%) in the placebo group (P < 0.001). Of those who did not have LVH
at baseline, 3 of 46 patients (6.5%) in the stevioside group had
developed LVH after 2 years, compared with 9 of 37 patients (24.3%) in
the placebo group (P < 0.001).
CONCLUSIONS: In this 2-year study in
Chinese patients with mild hypertension, oral stevioside significantly
decreased SBP and DBP compared with placebo. QOL was improved, and no
significant adverse effects were noted."

Cheers Alan, T2, Australia.
Remove weight and carbs to email.
--
dx May 2002 , A1C 8.2=>5.9, wt 117kg=>92kg,
No diabetes meds. Diet and not enough exercise.
I have no medical qualifications beyond my own experience.
Choose your advisers carefully, because experience can be
an expensive teacher.

Everything in Moderation - Except Laughter.
Cheers, Alan, T2 d&e, Australia.
Remove weight and carbs to email.
--
Everything in Moderation - Except Laughter.
*************************************************************

Clin Ther. 2003 Nov; 25(11): 2797-808.
Efficacy and tolerability of oral stevioside in patients with mild essential
hypertension: a two-year, randomized, placebo-controlled study.
Hsieh MH, Chan P, Sue YM, Liu JC, Liang TH, Huang TY, Tomlinson B, Chow MS,
Kao PF, Chen YJ.
Department of Medicine, Taipei Medical University--Wan Fang Hospital, Taipei
City, Taiwan.

BACKGROUND: Stevioside, a natural glycoside isolated from the plant Stevia
rebaudiana Bertoni, has been used as a commercial sweetening agent in Japan
and Brazil for >20 years.
Previous animal and human studies have indicated that stevioside has an
antihypertensive effect.
OBJECTIVES: This study was undertaken to investigate the long-term (2-year)
efficacy and tolerability of stevioside in patients with mild essential
hypertension. Secondary objectives were to determine the effects of
stevioside on left ventricular mass index (LVMI) and quality of life (QOL).
METHODS: This was a multicenter, randomized, double-blind,
placebo-controlled trial in Chinese men and women aged between 20 and 75
years with mild essential hypertension (systolic blood pressure [SBP]
140-159 mm Hg and diastolic blood pressure [DBP] 90-99 mm Hg).
Patients took capsules containing 500 mg stevioside powder or placebo 3
times daily for 2 years.
Blood pressure was measured at monthly clinic visits; patients were also
encouraged to monitor blood pressure at home using an automated device. LVMI
was determined by 2-dimensional echocardiography at baseline and after 1 and
2 years of treatment.
QOL [ Quality Of Life ] was assessed using the Medical Outcomes Study
36-Item Short-Form Health Survey.
Electrocardiographic, laboratory, and QOL parameters were assessed at the
beginning of treatment, and at 6 months, 1 year, and 2 years.
RESULTS: One hundred seventy-four patients (87 men, 87 women) were enrolled
in the study, and 168 completed it: 82 (42 men, 40 women; mean [SD] age, 52
[7] years) in the stevioside group and 86 (44 women, 42 men; mean age, 53
[7] years) in the placebo group.
After 2 years, the stevioside group had significant decreases in mean (SD)
SBP and DBP compared with baseline (SBP, from 150 [7.3] to 140 [6.8] mm Hg;
DBP, from 95 [4.2] to 89 [3.2] mm Hg; P < 0.05) and compared with placebo (P
< 0.05).
Based on patients' records of self-monitored blood pressure, these effects
were noted beginning approximately 1 week after the start of treatment and
persisted throughout the study.
There were no significant changes in body mass index or blood biochemistry,
and the results of laboratory tests were similar in the 2 groups throughout
the study.
No significant difference in the incidence of adverse effects was noted
between groups, and QOL scores were significantly improved overall with
stevioside compared with placebo (P < 0.001).
Neither group had a significant change in mean LVMI. However, after 2 years,
6 of 52 patients (11.5%) in the stevioside group had left ventricular
hypertrophy (LVH), compared with 17 of 50 patients (34.0%) in the placebo
group (P < 0.001).
Of those who did not have LVH at baseline, 3 of 46 patients (6.5%) in the
stevioside group had developed LVH after 2 years, compared with 9 of 37
patients (24.3%) in the placebo group (P < 0.001).
CONCLUSIONS: In this 2-year study in Chinese patients with mild
hypertension, oral stevioside significantly decreased SBP and DBP compared
with placebo.
QOL was improved, and no significant adverse effects were noted.
Publication Types: Clinical Trial Multicenter Study Randomized Controlled
Trial
PMID: 14693305


Metabolism. 2004 Jan; 53(1): 101-7.
Effects of stevioside on glucose transport activity in insulin-sensitive and
insulin-resistant rat skeletal muscle.
Lailerd N, Saengsirisuwan V, Sloniger JA, Toskulkao C, Henriksen EJ.
Muscle Metabolism Laboratory, Department of Physiology, University of
Arizona College of Medicine, Tuscon, USA.

Stevioside (SVS), a natural sweetener extracted from Stevia rebaudiana, has
been used as an antihyperglycemic agent.
However, little is known regarding its potential action on skeletal muscle,
the major site of glucose disposal.
Therefore, the purpose of the present study was to determine the effect of
SVS treatment on skeletal muscle glucose transport activity in both
insulin-sensitive lean (Fa/-) and insulin-resistant obese (fa/fa) Zucker
rats.
SVS was administered (500 mg/kg body weight by gavage) 2 hours before an
oral glucose tolerance test (OGTT).
Whereas the glucose incremental area under the curve (IAUC(glucose)) was not
affected by SVS in lean Zucker rats, the insulin incremental area under the
curve (IAUC(insulin)) and the glucose-insulin index (product of glucose and
insulin IAUCs and inversely related to whole-body insulin sensitivity) were
decreased (P<.05) by 42% and 45%, respectively.
Interestingly, in the obese Zucker rat, SVS also reduced the IAUC(insulin)
by 44%, and significantly decreased the IAUC(glucose) (30%) and the
glucose-insulin index (57%).
Muscle glucose transport was assessed following in vitro SVS treatment.
In lean Zucker rats, basal glucose transport in type I soleus and type IIb
epitrochlearis muscles was not altered by 0.01 to 0.1 mmol/L SVS.
In contrast, 0.1 mmol/L SVS enhanced insulin-stimulated (2 mU/mL) glucose
transport in both epitrochlearis (15%) and soleus (48%).
At 0.5 mmol/L or higher, the SVS effect was reversed.
Similarly, basal glucose transport in soleus and epitrochlearis muscles in
obese Zucker rats was not changed by lower doses of SVS (0.01 to 0.1
mmol/L). However, these lower doses of SVS significantly increased
insulin-stimulated glucose transport in both obese epitrochlearis and soleus
(15% to 20%).
In conclusion, acute oral SVS increased whole-body insulin sensitivity, and
low concentrations of SVS (0.01 to 0.1 mmol/L) modestly improved in vitro
insulin action on skeletal muscle glucose transport in both lean and obese
Zucker rats. These results indicate that one potential site of action of SVS
is the skeletal muscle glucose transport system. PMID: 14681850


Metabolism. 2004 Jan; 53(1): 73-6.
Antihyperglycemic effects of stevioside in type 2 diabetic subjects.
Gregersen S, Jeppesen PB, Holst JJ, Hermansen K.
Department of Endocrinology and Metabolism C, Aarhus University Hospital,
Denmark.

Stevioside is present in the plant Stevia rebaudiana Bertoni (SrB).
Extracts of SrB have been used for the treatment of diabetes in, for
example, Brazil, although a positive effect on glucose metabolism has not
been unequivocally demonstrated.
We studied the acute effects of stevioside in type 2 diabetic patients.
We hypothesize that supplementation with stevioside to a test meal causes a
reduction in postprandial blood glucose.
Twelve type 2 diabetic patients were included in an acute, paired cross-over
study.
A standard test meal was supplemented with either 1 g of stevioside or 1 g
of maize starch (control).
Blood samples were drawn at 30 minutes before and for 240 minutes after
ingestion of the test meal.
Compared to control, stevioside reduced the incremental area under the
glucose response curve by 18% (P =.013).
The insulinogenic index (AUC(i,insulin)/AUC(i,glucose)) was increased by
approximately 40% by stevioside compared to control (P <.001).
Stevioside tended to decrease glucagon levels, while it did not
significantly alter the area under the insulin, glucagon-like peptide 1, and
glucose-dependent insulinotropic polypeptide curves.
In conclusion, stevioside reduces postprandial blood glucose levels in type
2 diabetic patients, indicating beneficial effects on the glucose
metabolism. Stevioside may be advantageous in the treatment of type 2
diabetes.
Publication Types: Clinical Trial Randomized Controlled Trial
PMID: 14681845

Br J Clin Pharmacol. 2000 Sep; 50(3): 215-20.
A double-blind placebo-controlled study of the effectiveness and
tolerability of oral stevioside in human hypertension.
Chan P, Tomlinson B, Chen YJ, Liu JC, Hsieh MH, Cheng JT.
Division of Cardiovascular Medicine, Taipei Medical College and affiliated
Taipei Wan Fang Hospital, Taiwan.

AIMS: Stevioside is a natural plant glycoside isolated from the plant Stevia
rebaudiana which has been commercialized as a sweetener in Japan for more
than 20 years.
Previous animal studies have shown that stevioside has an antihypertensive
effect. This study was to designed to evaluate the effect of stevioside in
human hypertension.
METHODS: A multicentre, randomized, double-blind, placebo-controlled study
was undertaken.
This study group consisted of 106 Chinese hypertensive subjects with
diastolic blood pressure between 95 and 110 mmHg and ages ranging from 28 to
75 years with 60 subjects (men 34, women 26; mean +/- s.d., 54.1+/-3.8
years) allocated to active treatment and 46 (men 19, women 27; mean +/-
s.d., 53.7+/-4.1 years) to placebo treatment.
Each subject was given capsules containing stevioside (250 mg) or placebo
thrice daily and followed-up at monthly intervals for 1 year.
RESULTS: After 3 months, the systolic and diastolic blood pressure of the
stevioside group decreased significantly (systolic: 166.0+/-9.4-152.6+/-6.8
mmHg; diastolic: 104.7 +/- 5.2-90.3+/-3.6 mmHg, P<0.05),
and the effect persisted during the whole year.
Blood biochemistry parameters including lipid and glucose showed no
significant changes.
No significant adverse effect was observed and quality of life assessment
showed no deterioration.
CONCLUSIONS: This study shows that oral stevioside is a well tolerated and
effective modality that may be considered as an alternative or supplementary
therapy for patients with hypertension. Publication Types: Clinical Trial
Multicenter Study Randomized Controlled Trial PMID: 10971305

Phytochemistry. 2003 Nov; 64(5): 913-21.
Stevioside.
Geuns JM.
Laboratory of Plant Physiology, Catholic University of Leuven, Kasteelpark
Arenberg 31, B 3001 Leuven, Belgium. jan.geuns@...

Stevioside is a natural sweetener extracted from leaves of Stevia rebaudiana
(Bertoni) Bertoni.
The literature about Stevia, the occurrence of its sweeteners, their
biosynthetic pathway and toxicological aspects are discussed.
Injection experiments or perfusion experiments of organs are considered as
not relevant for the use of Stevia or stevioside as food, and therefore
these studies are not included in this review.
The metabolism of stevioside is discussed in relation with the possible
formation of steviol.
Different mutagenicity studies as well as studies on carcinogenicity are
discussed. Acute and subacute toxicity studies revealed a very low toxicity
of Stevia and stevioside.
Fertility and teratogenicity studies are discussed as well as the effects on
the bio-availability of other nutrients in the diet.
The conclusion is that Stevia and stevioside are safe when used as a
sweetener. It is suited for both diabetics, and PKU patients, as well as for
obese persons intending to lose weight by avoiding sugar supplements in the
diet.
No allergic reactions to it seem to exist.
Publication Types: Review Review Literature PMID: 14561506


J Agric Food Chem. 2003 Oct 22; 51(22): 6618-22.
Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts
by human microflora.
Gardana C, Simonetti P, Canzi E, Zanchi R, Pietta P.
Department of Food Science and Microbiology, Division of Human Nutrition,
University of Milan, Via Celoria 2, 20133 Milan, Italy.

Stevia rebaudiana standardized extracts (SSEs) are used as natural
sweeteners or dietary supplements in different countries for their content
of stevioside or rebaudioside A.
These compounds possess up to 250 times the sweetness intensity of sucrose,
and they are noncaloric and noncariogenic sweeteners.
The aim of this study was to investigate the in vitro transformation of
stevioside and rebaudioside A after incubation with human microflora, the
influence of these sweeteners on human microbial fecal community and which
specific groups metabolize preferentially stevioside and rebaudioside A.
The experiments were carried out under strict anaerobic conditions in batch
cultures inoculated with mixed fecal bacteria from volunteers.
The hydrolysis was monitored by HPLC coupled to photodiode array and mass
spectrometric detectors.
Isolated bacterial strains from fecal materials incubated in selective
broths were added to stevioside and rebaudioside A.
These sweeteners were completely hydrolyzed to their aglycon steviol in 10
and 24 h, respectively.
Interestingly, the human intestinal microflora was not able to degrade
steviol. Furthermore, stevioside and rebaudioside A did not significantly
influence the composition of fecal cultures;
among the selected intestinal groups, bacteroides were the most efficient in
hydrolyzing Stevia sweeteners to steviol. PMID: 14558786


Metabolism. 2003 Mar; 52(3): 372-8.
Antihyperglycemic and blood pressure-reducing effects of stevioside in the
diabetic Goto-Kakizaki rat.
Jeppesen PB, Gregersen S, Rolfsen SE, Jepsen M, Colombo M, Agger A, Xiao J,
Kruhoffer M, Orntoft T, Hermansen K.
Department of Endocrinology and Metabolism, Molecular Diagnostic Laboratory,
Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark.

Stevioside, a glycoside present in the leaves of the plant, Stevia
rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro.
Its potential antihyperglycemic and blood pressure-lowering effects were
examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat.
Rats were fed 0.025 g x kg(-1) x d(-1) of stevioside (purity > 99.6%) for 6
weeks.
An intra-arterial catheter was inserted into the rats after 5 weeks, and
conscious rats were subjected to arterial glucose tolerance test (2.0 g x
kg(-1)) during week 6.
Stevioside had an antihyperglycemic effect (incremental area under the
glucose response curve [IAUC]):
985 +/- 20 (stevioside) versus 1,575 +/- 21 (control) mmol/L x 180 minutes,
(P <.05),
it enhanced the first-phase insulin response (IAUC: 343 +/- 33 [stevioside]
v 136 +/- 24 [control] microU/mL insulin x 30 minutes, P <.05)
and concomitantly suppressed the glucagon levels (total AUC: 2,026 +/- 234
[stevioside] v 3,535 +/- 282 [control] pg/mL x 180 minutes, P <.05).
In addition, stevioside caused a pronounced suppression of both the systolic
(135 +/- 2 v 153 +/- 5 mm Hg; P <.001) and the diastolic blood pressure (74
+/- 1 v 83 +/- 1 mm Hg; P <.001).
Bolus injections of stevioside (0.025 g x kg(-1)) did not induce
hypoglycemia. Stevioside augmented the insulin content in the beta-cell
line, INS-1.
Stevioside may increase the insulin secretion, in part, by induction of
genes involved in glycolysis.
It may also improve the nutrient-sensing mechanisms, increase cytosolic
long-chain fatty acyl-coenzyme A (CoA), and downregulate phosphodiesterase 1
(PDE1) estimated by the microarray gene chip technology.
In conclusion, stevioside enjoys a dual positive effect by acting as an
antihyperglycemic and a blood pressure-lowering substance; effects that may
have therapeutic potential in the treatment of type 2 diabetes and the
metabolic syndrome. Copyright 2003, Elsevier Science (USA). All rights
reserved.
PMID: 12647278


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

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

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 rmforall
[ Also 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.]

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 rmforall [A detailed look at the data] ]

Pharmacology. 2003 Jan; 67(1): 14-20.
Mechanism of the antihypertensive effect of stevioside in anesthetized dogs.
Liu JC, Kao PK, Chan P, Hsu YH, Hou CC, Lien GS, Hsieh MH, Chen YJ, Cheng
JT.
Department of Medicine, Taipei Medical University--Wan Fang Hospital,
Taipei, Taiwan.

Stevioside is a sweet-tasting glycoside isolated from the leaves of Stevia
rebaudiana.
It has been used as a noncaloric sugar substitute in Japan and Brazil for
decades. Previous studies have shown that it lowered blood pressure in
spontaneously hypertensive rats by intravenous injection.
This study was designed to evaluate the hypotensive effect of stevioside in
dogs and to define the underlying mechanism.
After nasogastric administration of stevioside powder (200 mg/kg), the blood
pressure of healthy mongrel dogs began to significantly decrease at 60 min
and returned to baseline level at 180 min.
The reduction of blood pressure was more rapid (at 5-10 min) and effective
after intravenous injection.
However, no significant change of blood pressure was noted after injection
through left vertebral artery, implicating that the hypotensive effect is
not related to the central nervous system.
Stevioside also showed significant hypotensive effects in renal hypertensive
dogs, in a dose-dependent manner.
In cultured rat aortic smooth muscle cells (A7r5 cell line), stevioside can
dose-dependently inhibit the stimulatory effects of vasopressin and
phenylephrine on intracellular Ca(2+) in a calcium-containing medium.
However, no intracellular Ca(2+) inhibitory effect was observed in
calcium-free medium, implicating that stevioside may inhibit the Ca(2+)
influx from extracellular fluid.
Our present data show that stevioside did not influence the calcium
ionophore (A23187) induced Ca(2+) influx, indicating that the antagonistic
effect was through Ca(2+) channels.
This study confirmed that stevioside is an effective antihypertensive
natural product, and its hypotensive mechanism may be probably due to
inhibition of the Ca(2+) influx. Copyright 2003 S. Karger AG, Basel
PMID: 12444299


Biol Pharm Bull. 2002 Nov; 25(11): 1488-90.
Inhibitory effect of stevioside on tumor promotion by
12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse
skin.
Yasukawa K, Kitanaka S, Seo S. yasukawa@...
College of Pharmacy, Nihon University, Chiba, Japan.

Four steviol (ent-kaurene-type diterpenoid) glycosides, stevioside,
rebaudiosides A and C, and dulcoside A, have been isolated from Stevia
rebaudiana BERTONI.
These compounds showed strong inhibitory activity against
12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice.
The 50% inhibitory dose of these compounds for TPA-induced inflammation was
54.1-291.6 micro g/ear.
Furthermore, at 1.0 and 0.1 mg/mouse of stevioside mixture, the mixture of
these compounds markedly inhibited the promoting effect of TPA (1 micro
g/mouse) on skin tumor formation initiated with
7,12-dimethylbenz[a]anthracene (50 micro g/mouse). PMID: 12419967

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

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

Zhonghua Yi Xue Za Zhi (Taipei). 2002 Jan; 65(1): 1-6.
Antihypertensive effect of stevioside in different strains of hypertensive
rats.
Hsu YH, Liu JC, Kao PF, Lee CN, Chen YJ, Hsieh MH, Chan P.
Department of Medicine, Taipei Medical University-Wan Fang Hospital, Taiwan,
ROC.

BACKGROUND: Stevioside is a natural sweet-tasting glycoside isolated from
the herb Stevia rebaudiana, composed of stevia, a diterpenic carboxylic
alcohol with three glucose molecules, mainly used commercially as sugar
substitute.
Previous study has shown that it can lower blood pressure in anesthetized
spontaneously hypertensive rats (SHR).
This study was undertaken to evaluate the antihypertensive effect of
stevioside in different strains of hypertensive rats and to observe whether
there is difference in blood pressure lowering effect.
METHODS: Noninvasive tail-cuff method was employed to measure blood
pressure.
Stevioside at the concentrations of 50, 100 and 200 mg/kg were administered
intraperitoneally (ip) to normotensive Wistar-Kyoto rats (NTR), SHR,
deoxycorticosterone acetate-salt (DOCA-NaCl) sensitive hypertensive rats
(DHR) and renal hypertensive rats (RHR).
RESULTS: Significant hypotensive effect of stevioside administered ip was
noted in different strains of rats at the dose of 50 mg/kg.
When stevioside was increased to the concentrations of 100 and 200 mg/kg,
ip, it also caused slow and persistent lowering of blood pressure in SHR and
NTR. Data also showed that stevioside given at the concentrations of 100,
200 and 400 mg/kg ip resulted in lowering of blood pressure in SHR
dose-dependently. Blood pressure returned to previous levels after the drug
was discontinued for 2-3 days.
Drinking of 0.1% stevioside solution in mature SHR could have
antihypertensive effect and also prevented hypertension in immature SHR.
CONCLUSIONS: This study reconfirmed stevioside has hypotensive effect and
the effect is more prominent in hypertensive rats. PMID: 11939668


Phytomedicine. 2002 Jan; 9(1): 9-14.
Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic
effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats.
Jeppesen PB, Gregersen S, Alstrup KK, Hermansen K.
Department of Endocrinology and Metabolism C, Aarhus University Hospital,
Denmark. pbj@...

Extracts of leaves from the plant Stevia rebaudiana Bertoni have been used
in the traditional treatment of diabetes in Paraguay and Brazil.
Recently, we demonstrated a direct insulinotropic effect in isolated mouse
islets and the clonal beta cell line INS-1 of the glycoside stevioside that
is present in large quantity in these leaves.
Type 2 diabetes is a chronic metabolic disorder that results from defects in
both insulin and glucagon secretion as well as insulin action.
In the present study we wanted to unravel if stevioside in vivo exerts an
antihyperglycaemic effect in a nonobese animal model of type 2 diabetes.
An i.v. glucose tolerance test (IVGT) was carried out with and without
stevioside in the type 2 diabetic Goto-Kakizaki (GK) rat, as well as in the
normal Wistar rat.
Stevioside (0.2 g/kg BW) and D-glucose (2.0 g/kg BW) were administered as
i.v. bolus injections in anaesthetized rats.
Stevioside significantly suppressed the glucose response to the IVGT in GK
rats (incremental area under the curve (IAUC): 648 +/- 50 (stevioside) vs
958 +/- 85 mM x 120 min (control); P < 0.05)
and concomitantly increased the insulin response (IAUC: 51116 +/- 10967
(stevioside) vs 21548 +/- 3101 microU x 120 min (control); P < 0.05).
Interestingly, the glucagon level was suppressed by stevioside during the
IVGT, (total area under the curve (TAUC): 5720 +/- 922 (stevioside) vs 8713
+/- 901 pg/ml x 120 min (control); P < 0.05).
In the normal Wistar rat stevioside enhanced insulin levels above basal
during the IVGT (IAUC: 79913 +/- 3107 (stevioside) vs 17347 +/- 2882 microU
x 120 min (control); P < 0.001), however, without altering the blood glucose
response (IAUC: 416 +/- 43 (stevioside) vs 417 +/- 47 mM x 120 min
(control)) or the glucagon levels (TAUC: 5493 +/- 527 (stevioside) vs 5033
+/- 264 pg/ml x 120 min (control)).
In conclusion, stevioside exerts antihyperglycaemic, insulinotropic, and
glucagonostatic actions in the type 2 diabetic GK rat, and may have the
potential of becoming a new antidiabetic drug for use in type 2 diabetes.
PMID: 11924770

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.

Stevioside is a sweet-tasting glycoside occurring abundantly in the leaves
of Stevia rebaudiana (Compositae).
It has been used popularly in Japan and Brazil as a sugar substitute for
decades. Previous study has shown that it lowered blood pressure in
spontaneously hypertensive rats (SHRs) when administered intravenously.
This study shows that intraperitoneal injection of stevioside 25 mg/kg also
has antihypertensive effect in SHRs.
In isolated aortic rings from normal rats, stevioside could dose-dependently
relax the vasopressin-induced vasoconstriction in both the presence and
absence of endothelium.
However, stevioside had no effect on phenylephrine- and KCl-induced phasic
vasoconstriction.
In addition, stevioside lost its influence on vasopressin-induced
vasoconstriction in Ca(2+)-free medium.
The results indicate that stevioside caused vasorelaxation via an inhibition
of Ca(2+) influx into the blood vessel.
This phenomenon was further confirmed in cultured aortic smooth muscle cells
(A7r5). Using 10(-5) M methylene blue for 15 min, stevioside could still
relax 10(-8) M vasopressin-induced vasoconstriction in isolated rat aortic
rings, showing that this vasorelaxation effect was not related to nitric
oxide.
The present data show that the vasorelexation effect of stevioside was
mediated mainly through Ca(2+) influx inhibition. PMID: 11745013

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-tak@...

Anti-human rotavirus (HRV) activity of hot water extracts from Stevia
rebaudiana (SE) was examined.
SE inhibited the replication of all four serotypes of HRV in vitro.
This inhibitory effect of SE was not reduced on the prior exposure of SE to
HCl for 30 min at pH 2.
Binding assay with radiolabeled purified viruses indicated that the
inhibitory mechanism of SE is the blockade of virus binding.
The SE inhibited the binding of anti-VP7 monoclonal antibody to HRV-infected
MA104 cells.
The inhibitory components of SE were found to be heterogeneous anionic
polysaccharides with different ion charges.
The component analyses suggested that the purified fraction named as
Stevian with the highest inhibitory activity consists of the anionic
polysaccharide with molecular weight of 9800, and contains Ser and Ala as
amino acids.
Analyses of sugar residues suggest uronic acid(s) as sugar components.
It did not contain amino and neutral sugars and sulfate residues.
These findings suggest that SE may bind to 37 kD VP7 and interfere with the
binding of VP7 to the cellular receptors by steric hindrance, which results
in the blockade of the virus attachment to cells. PMID: 11166857

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.

The natural sweetener stevioside, which is found in the plant Stevia
rebaudiana Bertoni, has been used for many years in the treatment of
diabetes among Indians in Paraguay and Brazil.
However, the mechanism for the blood glucose-lowering effect remains
unknown.
To elucidate the impact of stevioside and its aglucon steviol on insulin
release from normal mouse islets and the beta-cell line INS-1 were used.
Both stevioside and steviol (1 nmol/L to 1 mmol/L) dose-dependently enhanced
insulin secretion from incubated mouse islets in the presence of 16.7 mmol/L
glucose (P < .05).
The insulinotropic effects of stevioside and steviol were critically
dependent on the prevailing glucose concentration, ie, stevioside (1 mmol/L)
and steviol (1 micromol/L) only potentiated insulin secretion at or above
8.3 mmol/L glucose (P < .05).
Interestingly, the insulinotropic effects of both stevioside and steviol
were preserved in the absence of extracellular Ca2+.
During perifusion of islets, stevioside (1 mmol/L) and steviol (1
micromol/L) had a long-lasting and apparently reversible insulinotropic
effect in the presence of 16.7 mmol/L glucose (P < .05).
To determine if stevioside and steviol act directly on beta cells, the
effects on INS-1 cells were also investigated.
Stevioside and steviol both potentiated insulin secretion from INS-1 cells
(P < .05). Neither stevioside (1 to 100 micromol/L) nor steviol (10 nmol/L
to 10 micromol/L) influenced the plasma membrane K+ adenosine triphosphate
((K+)ATP)-sensitive channel activity, nor did they alter cyclic adenosine
monophosphate (cAMP) levels in islets.
In conclusion, stevioside and steviol stimulate insulin secretion via a
direct action on beta cells.
The results indicate that the compounds may have a potential role as
antihyperglycemic agents in the treatment of type 2 diabetes mellitus.
PMID: 10690946


J Ethnopharmacol. 1999 Nov 1; 67(2): 157-61.
Effects of chronic administration of Stevia rebaudiana on fertility in rats.
Melis MS. msmelis@...
Departamento de Biologia, Setor de Fisiologia, Faculdade de Filosofia,
Ciencias e Letras, Universidade de Sao Paulo, Ribeirao Preto, Brazil.

A study conducted on prepubertal male rats showed that chronic
administration (60 days) of a Stevia rebaudiana aqueous extract produced a
decrease in final weight of testis, seminal vesicle and cauda epididymidis.
In addition, the fructose content of the accessory sex glands and the
epididymal sperm concentration are decreased. Stevia treatment tended to
decrease the plasma testosterone level, probably by a putative affinity of
glycosides of extract for a certain androgen receptor, and no alteration
occurred in luteinizing hormone level. These data are consistent with the
possibility that Stevia extracts may decrease the fertility of male rats.
PMID: 10619379


Life Sci. 1998; 63(19): 1679-84.
The effect of stevioside on blood pressure and plasma catecholamines in
spontaneously hypertensive rats.
Chan P, Xu DY, Liu JC, Chen YJ, Tomlinson B, Huang WP, Cheng JT.
Division of Cardiovascular Medicine, Taipei Medical College Hospital and
affiliated Taipei Wan Fang Hospital, Taiwan, ROC.

Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic
carboxylic alcohol with three glucose molecules, mainly used as a substitute
for non-alcoholic sweetener.
It has previously been shown to reduce blood pressure in studies in animals
and human.
The effect of intravenous stevioside on the blood pressure was studied in
spontaneously hypertensive rats (SHR).
The hypotensive effect on both systolic and diastolic blood pressure was
dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious
SHR. The maximum reductions in systolic and diastolic blood pressure were
31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the
hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg.
Serum dopamine, norepinephrine and epinephrine levels were not changed
significantly 60 min after intravenous injection of stevioside 100 mg/kg in
anesthetized SHR.
The present data show that stevioside given intravenously to conscious SHR
was effective in blood pressure reduction and there was no change in serum
catecholamines in anaesthetized animals with this natural compound.
PMID: 9806223


Microbiol Immunol. 1997; 41(12): 1005-9.
Bactericidal activity of a fermented hot-water extract from Stevia
rebaudiana Bertoni towards enterohemorrhagic Escherichia coli O157:H7 and
other food-borne pathogenic bacteria. tomita@...
Tomita T, Sato N, Arai T, Shiraishi H, Sato M, Takeuchi M, Kamio Y.
Faculty of Agriculture, Tohoku University, Sendai, Miyagi, Japan.

A fermented aqueous extract from Stevia rebaudiana Bertoni showed strong
bactericidal activity towards a wide range of food-borne pathogenic bacteria
including enterohemorrhagic Escherichia coli O157:H7.
The colony-forming ability of the food-borne pathogenic bacteria tested so
far was reduced to < 10(-7) when exposed to > or = 40% (v/v) solutions of
the fermented extract at 37 C for 2 hr.
Secretion of verocytotoxin 1 and 2 by enterohemorrhagic E. coli was also
diminished by fermented extract at a concentration of > or = 10% (v/v).
In contrast, the fermented extract did not significantly kill Bifidobacteria
or Lactobacilli.
The active principle(s) of the fermented Stevia extract were bactericidal
under acidic conditions. PMID: 9492187


J Med Assoc Thai. 1997 Sep; 80 Suppl 1: S121-8.
Lack of mutagenicity of stevioside and steviol in Salmonella typhimurium TA
98 and TA 100.
Klongpanichpak S, Temcharoen P, Toskulkao C, Apibal S, Glinsukon T.
Department of Physiology, Faculty of Science, Mahidol University, Bangkok,
Thailand.

Stevioside, a sweet-tasting diterpene glycoside derived from Stevia
rebaudiana, and steviol, a product from enzymatic hydrolysis of stevioside,
were tested for mutagenic activity by the in vitro Ames test, a
preincubation method, using Salmonella typhimurium TA 98 and TA 100 as the
tester strains, either in the presence or absence of metabolic activating
system derived from the sodium phenobarbital and 5,6-benzoflavone pretreated
liver S9 fractions from various animal species including rat, mouse, hamster
and guinea pig.
Stevioside and steviol at the concentrations up to 50 mg and 2 mg per plate,
respectively showed no mutagenic effect on both tester strains either in the
presence or absence of metabolic activating system.
However, at the high concentration both stevioside and steviol showed some
toxic effects on both tester strains.
The toxic effect was decreased in the presence of the metabolic activating
system. PMID: 9347659


Mutagenesis. 1996 Nov; 11(6): 573-9.
Evaluation of the genotoxicity of stevioside and steviol using six in vitro
and one in vivo mutagenicity assays.
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.
Division of Genetics and Mutagenesis, National Institute of Health Sciences,
Tokyo, Japan.

Stevioside, a constituent of Stevia rebaudiana, is commonly used as a
non-caloric sugar substitute in Japan.
The genetic toxicities of stevioside and its aglycone, steviol, were
examined with seven mutagenicity tests using bacteria (reverse mutation
assay, forward mutation assay, umu test and rec assay), cultured mammalian
cells (chromosomal aberration test and gene mutation assay) and mice
(micronucleus test).
Stevioside was not mutagenic in any of the assays examined.
The aglycone, steviol, however, produced dose-related positive responses in
some mutagenicity tests, i.e. the forward mutation assay using Salmonella
typhimurium TM677, the chromosomal aberration test using Chinese hamster
lung fibroblast cell line (CHL) and the gene mutation assay using CHL.
Metabolic activation systems containing 9000 g supernatant fraction (S9) of
liver homogenates prepared from polychlorinated biphenyl or phenobarbital
plus 5,6-benzoflavone-pretreated rats were required for mutagenesis and
clastogenesis. Steviol was weakly positive in the umu test using
S.typhimurium TA1535/pSK1002 either with or without the metabolic activation
system. Steviol, even in the presence of the S9 activation system, was
negative in other assays, i.e. the reverse mutation assays using
S.typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and
Escherichia coli WP2 uvrA/pKM101 and the rec-assay using Bacillus subtilis.
Steviol was negative in the mouse micronucleus test.
The genotoxic risk of steviol to humans is discussed. PMID: 8962427


Braz J Med Biol Res. 1996 May; 29(5): 669-75.
A crude extract of Stevia rebaudiana increases the renal plasma flow of
normal and hypertensive rats.
Melis MS.
Departamento de Biologia, Faculdade de Filosofia, Ciencias e Letras de
Ribeirao Preto, Universidade de Sao Paulo, Brasil.

The effect of S. rebaudiana extract on renal function was evaluated in
normotensive and in experimental renal hypertensive rats (GII) using
clearance techniques.
Experiments were performed on male Wistar rats weighing 300-330 g (10
animals per group).
Goldblatt GII experimental hypertension was induced by placing a silver clip
with an internal gap of 0.25 mm around the left renal artery under ether
anesthesia. The contralateral kidney was left untouched.
Stevia was administered 10-12 weeks after clipping.
Oral-administration of Stevia extract, corresponding to 2.67 g dry
leaves/day for 30 days, resulted in a significant decrease in mean arterial
pressure in both the normo-(N) and hypertensive rats (H) (N rats: 113 +/-
3.0 mmHg in the control (C) group vs 69.5 +/- 4.0 mmHg in the Stevia (S)
group; H rats: 155 +/- 3.0 mmHg in C vs 108 +/- 4.0 mmHg in S; P < 0.05).
Glomerular filtration rate was constant in the N rats and increased
significantly in the H rats after Stevia treatment 16.47 +/- 1.29 vs 14.2
+/- 1.33 ml min-1 kg-1 in the C and S groups, respectively, P < 0.05).
Normo- and hypertensive rats presented an increase in renal plasma flow
following oral Stevia administration (N rats: 16.4 +/- 3.10 ml min-1 kg-1 in
the C group vs 33.3 +/- 3.20 ml min-1 kg-1 in the S group. P < 0.05; H rats:
19.30 +/- 2.45 ml min-1 kg-1 in the C group vs 37.0 +/- 3.93 ml min-1 kg-1
in the S group, P < 0.05).
Stevia administration provoked an increase in urinary flow in both N and H
animals (1.37 +/- 0.08% vs 2.32 +/- 0.11%, P < 0.05 and 1.47 +/- 0.07% vs
2.96 +/- 0.13%, P < 0.05 in N and H rats, respectively).
Sodium excretion increased in N and H animals after Stevia treatment (N
rats: 0.61 +/- 0.07% in the C group vs 1.55 +/- 0.20% in the S group, P <
0.05; H rats: 0.70 +/- 0.10% in the C group vs 2.22 +/- 0.45% in the S
group, P < 0.05).
These results are consistent with impairment of a renal autoregulation
mechanism in this hypertensive model after Stevia administration.
In conclusion, it was shown that Stevia extract, at doses higher than used
for sweetening purposes, is a vasodilator agent in normo- and hypertensive
animals.
PMID: 9033821


J Ethnopharmacol. 1995 Jul 28; 47(3): 129-34.
Chronic administration of aqueous extract of Stevia rebaudiana in rats:
renal effects.
Melis MS.
Departamento de Biologia, Faculdade de Filosofia, Ciencias e Letras
Universidade de Sao Paulo, Ribeirao Preto, Brazil.

The effects of administration of Stevia rebaudiana extracts for 20, 40 and
60 days on renal function and mean arterial pressure in normal Wistar rats
were evaluated.
Results showed that the Stevia rebaudiana treated rats group for 20 days did
not significantly differ from the control group.
Chronic administration of a crude extract for 40 and 60 days induced
hypotension, diuresis and natriuresis with glomerular filtration rate (GFR)
constant.
An increase of the renal plasma flow (RPF) was exclusively observed for the
group treated for 60 days.
The results suggests that oral administration to rats of an aqueous extract
of Stevia dried leaves induce systemic and renal vasodilation, causing
hypotension, diuresis and natriuresis. PMID: 8569236


Res Commun Chem Pathol Pharmacol. 1994 Apr; 84(1): 111-8.
Influence of stevioside on hepatic glycogen levels in fasted rats.
Hubler MO, Bracht A, Kelmer-Bracht AM.
Laboratory of Liver Metabolism, University of Maringa, Brazil.

The influence of stevioside, the sweet glycoside of Stevia rebaudiana
leaves, on the glycogen levels of fasted rats was investigated.
In one set of experiments, single doses of stevioside (200 mumol) or steviol
(200 mumol) were given orally to 24-hours fasted rats, either alone or
simultaneously with fructose.
Under these conditions both stevioside and steviol increased the initial
glycogen deposition in the liver.
In another set of experiments, stevioside was given to the rats in the
drinking water at the beginning of the fasting periods (5:00 p.m.) of 24 and
48 hours.
Two different concentrations were given, 1.0 and 2.0 mM.
Increased hepatic glycogen levels were found at 48 hours with stevioside
(1.0 mM) and at 24 hours with stevioside (2.0 mM).
Steviol had no effect on hepatic glycogen levels when given in the drinking
water. It can be concluded that stevioside exerts a stimulatory action on
hepatic glycogen synthesis under gluconeogenic conditions. PMID: 8042003


Environ Health Perspect. 1993 Oct; 101 Suppl 3: 53-6.
Mutagenicity and human chromosomal effect of stevioside, a sweetener from
Stevia rebaudiana Bertoni.
Suttajit M, Vinitketkaumnuen U, Meevatee U, Buddhasukh D.
Department of Biochemistry, Chiang Mai University, Thailand.

Leaves of Stevia rebaudiana Bertoni have been popularly used as a sweetener
in foods and beverages for diabetics and obese people due to their potent
sweetener stevioside.
In this report, stevioside and steviol were tested for mutagenicity in
Salmonella typhimurium strains TA98 and TA100 and for chromosomal effects on
cultured human lymphocytes.
Stevioside was not mutagenic at concentrations up to 25 mg/plate, but showed
direct mutagenicity to only TA98 at 50 mg/plate.
However, steviol did not exhibit mutagenicity in either TA98 or TA100, with
or without metabolic activation.
No significant chromosomal effect of stevioside and steviol was observed in
cultured blood lymphocytes from healthy donors (n = 5).
This study indicates that stevioside and steviol are neither mutagenic nor
clastogenic in vitro at the limited doses; however, in vivo genotoxic tests
and long-term effects of stevioside and steviol are yet to be investigated.
PMID: 8143647
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http://groups.yahoo.com/group/aspartameNM/message/1071
research on aspartame (methanol, formaldehyde, formic acid) toxicity:
Murray 2004.05.17 rmforall

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

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 2002.12.23 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1039
three-page review: aspartame (methanol, formaldehyde) toxicity:
Murray 2003.11.22 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1026
brief aspartame review: formaldehyde toxicity: Murray 2003.09.11 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 2003.09.09 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 2004.03.30 rmforall [ 150 KB ]

http://groups.yahoo.com/group/aspartameNM/message/1070
critique of aspartame review, French Food Safety Agency AFSSA 2002.05.07
aspartamgb.pdf (18 pages, in English), Martin Hirsch:
Murray 2004.04.13

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall EU Scientific Committee on Food, a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/989 On 2003.04.10
the European Union Parliament voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 2003.04.12 rmforall

http://www.eatright.org/Nutritive(1).pdf
J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners. American Dietetic Association.

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association Feb 2004,
Valerie B. Duffy & Madeleine J. Sigman-Grant: Murray 2004.05.14 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
121 members, 1084 posts in a public searchable archive

http://groups.yahoo.com/group/aspartame/messages
796 members, 16,891 posts in a public, searchable archive

It is certain that high levels of aspartame use, above 2 liters daily for
months and years, must lead to chronic formaldehyde-formic acid toxicity.

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).
The methanol is immediately released into the body after drinking--
unlike the large levels of methanol locked up in complex molecules inside
many fruits and vegetables.
Within hours, the liver turns much of the methanol into formaldehyde, and
then much of that into formic acid, both of which in time are partially
eliminated as carbon dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month, accumulating in and affecting every tissue.

If only 10% of the methanol is retained daily as formaldehyde, that would
give 12 mg daily formaldehyde accumulation-- about 60 times more than the
0.2 mg from 10% retention of the 2 mg EPA daily limit for formaldehyde in
drinking water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
Murray 2002.05.30 rmforall

This long-term low-level chronic toxic exposure leads to typical patterns of
increasingly severe complex symptoms, starting with headache, fatigue, joint
pain, irritability, memory loss, rashes, and leading to vision and eye
problems, and even seizures. In many cases there is addiction. Probably
there are immune system disorders, with a hypersensitivity to these toxins
and other chemicals.

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put into
the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours, with little
additional elimination, as carbon dioxide in exhaled air and as water in
the urine.
They did not mention that this meant that about 30% of the methanol must
transform into formaldehyde and then into formic acid, both of which must
remain as toxic products in all parts of the body.
They did not report any studies on the distribution of radioactivity in body
tissues, except that blood plasma proteins after 4 days held 4% of the
initial methanol.
This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg, about 1
part per million [ppm] of the acute toxicity level of 2,000 mg/kg, 67,000
mmol/kg, used by McMartin (1979).
Two L daily use of diet soda provides 123 mg methanol, 2 mg/kg for a 60 kg
person, a dose of 67 mmole/kg, a thousand times more than the dose in this
study.
By eight hours excretion of the dose in air and urine had leveled off at
67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine, so 68.7
% was excreted, and 31.3% was retained.
This data is the average of 4 monkeys.
"...the 14C in the feces was negligible."

"That fraction not so excreted (about 31%) was converted to body
constituents through the one-carbon metabolic pool."
"All radioactivity measurements were counted to +-1% accuracy..."
This indicates that the results could not be claimed to have a precision of
a tenth of a percent. OK, so this is a nit-pick-- but I believe espousing
spurious accuracy is a sign of scientific insecurity.

The abstract ends, "It was concluded that aspartame was digested to its
three constituents that were then absorbed as natural constituents of the
diet."
Thus, the concept is very subtly insinuated that methanol, as a
constituent of aspartame, is absorbed as a natural constituent of the diet.
"Dietary methanol is derived in large part from fresh fruits and
vegetables."
This is a serious error, since the large amounts of methanol in fresh fruits
and vegetables are not readily released by human digestion. (W. C. Monte,
1984)
Nowhere in this report are mentioned the dread words, "formaldehyde" and
"formic acid".

Of course, methanol and formaldehyde toxicity studies are highly relevant to
the issue of aspartame toxicity. [ Aspartame has to be turned into its
toxic products, formaldehyde and formic acid, in the body, before it is
toxic, so some pro-aspartame reseach studies test aspartame outside the
body, and then proclaim that they have proved that it is not toxic. ]

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA: Gold:
Wilson: CIIN: Murray 2002.12.12 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH. toxicology@...
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text

http://www.drthrasher.org/formaldehyde_1990.html full text Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223. "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation." PMID: 2400243
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