Compiled By Rich Murray, MA
Room For All
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Posted: 26 July 2005
Stevia (stevioside) is safe: Prof. Jan M.C. Geuns: Murray 2005.07.06

Stevioside is safe
Press Conference by Prof. Jan M.C. Geuns
Lab. Functional Biology, KULeuven
Kasteelpark Arenberg 31 3001 Leuven - Belgium
+32-16-321510 e-mail:

Stevioside, the main sweet component in the leaves of Stevia rebaudiana (Bertoni) Bertoni tastes about 300 times sweeter than sucrose (0.4% solution).

As the incidence of diabetes type 2 and obesity is sharply increasing, the last one also due to too much fat and salt intake, stevioside is a good substitute for table sugar.

The yearly costs of these diseases were estimated to be 30 billion euro in Germany, 5 billion in Belgium and 300 billion USD in the USA. This sum includes the money for drugs, for hospitalisation, amputations, eye diseases going to blindness, treatment of heart and blood circulation problems, special diets, dental care, costs of the medical staff and so on. Assuming that the European population ( 454,000,000) is in a similar bad condition as the Belgian one, the costs may be estimated at about 225 billion euro! Even this might be an underestimation as it does not include social aspects and human suffering.

The advantages of stevioside as a dietary supplement (daily intake estimated to be below 200 mg) for human subjects are manifold.

It is stable, non-calorific, and it maintains good dental health by reducing the intake of sugar, and it opens the possibility for use by diabetic and phenylketonuria patients and obese persons.

High concentrations of stevioside (250 mg thrice a day up to 500 mg thrice a day) lower blood pressure of hypertensive patients. Blood biochemistry parameters including lipid and glucose showed no significant changes. No significant adverse effect was observed and a quality of life assessment showed no deterioration. No decrease of male potency was observed.

Moreover, stevioside possesses potential as treatment for type 2 diabetes. Recently it was demonstrated that oral intake of stevioside causes a clear-cut reduction in the glycaemic response to a test meal.

Brazil, Korea, Maleysia and Japan, Stevia leaves, stevioside and highly refined extracts are officially used as a low-calorie sweetener. In the USA, powdered Stevia leaves and refined extracts from the leaves have been used as a dietary supplement since 1995. In 2000, the European Commission refused to accept Stevia or stevioside as a novel food or food additive respectively because of a lack of critical scientific reports on Stevia and the discrepancies between cited studies with respect to possible toxicological effects of stevioside and especially its aglycon steviol.

In 2004 researchers of the KULeuven (Belgium) organised an international symposium on "The Safety of stevioside". Scientists from all over the world concluded that stevioside is safe:

The lobby against stevioside is trying to circulate rumours of effects on male fertility. Contrary to these rumours, stevioside does not influence male fertility.

High concentrations of stevioside can be used for lowering blood pressure even without affecting the male potency (as do some of the other drugs used in hypertension).

The false rumours are based on a nonsense experiment with rats. In that experiment, each rat was daily force-fed extracts from about 2.668 g of dry Stevia leaves per day, i.e. 5.34 % of the body weight!

This is a very large amount: 53.4 g Stevia leaves/kg BW at the start of the experiments (rats weighing about 50 g) and about 13.75 g/kg BW at the end (rats weighing about 194 g).

For an adult person of 65 kg this means extracts of 3.47 kg of dry Stevia leaves or about 34.7 kg fresh leaves/day, i.e. more than 50% of the body weight.

The significance of such experiments in which only one extremely large concentration was tested, should be questioned. If we assume a steviol glycoside content of 10%, this means that the young animals received 5.3 g steviol glycosides/kg BW and the older ones about 1.3 g/kg BW.

In the sixty-third meeting of the Joint Expert Committee for Food Additives of the WHO (JECFA; 8-17 June 2004), a temporary Allowable Daily Intake (ADI) of 2 mg/kg BW (expressed as steviol) has been accepted, a step in the right direction for the worldwide general acceptance of stevioside and related compounds. However, Jecfa asked for additional research on the effects of low and high concentrations in patients with hypo- and normotension, in insuline dependent and -independent diabetes, stability studies and a better specification of the steviol glycoside mixture. To organise this research, we urgently need 600,000 euro.

The "Proceedings of the first symposium on the "Safety of Stevioside" are available at Euprint, Parkbosstraat 3, 3001 Heverlee, Belgium. Email:


The editors acknowledge the "Onderzoeksraad KULeuven - Belgium" for grant OT/00/15 and the FWO for grant G.0111.01, Medherbs Germany, Specchiasol Italy, DIC Japan and Brulo-Beheer The Netherlands for their financial support.

Artificial sweetener sales soar, stevia and tagatose available: Murray 2005.03.31
Reply to Ferne Hudson, Tate & Lyle PLC, re Splenda (sucralose) policy: Murray 2005.02.08
UN FAO & WHO approve Steviol glycosides as sweetener June 2004, imports to UK no longer blocked: Martini: Murray 2004.10.17
26 stevia safety abstracts since 1993: aspartame vs stevia debate on, George Schmidt, OD: Murray 2004.05.25
Short review: research on aspartame (methanol, formaldehyde, formic acid) toxicity: Murray 2005.07.06
Research on aspartame (methanol, formaldehyde, formic acid) toxicity: Murray 2004.04.29
Methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full plain text, 2001: substantial sources are degradation of fruit pectins, liquors, aspartame, smoke: Murray 2005.04.02

Fully 11% of aspartame is methanol-- 1,120 mg aspartame in 2 L diet soda, almost six 12-oz cans, gives 123 mg methanol (wood alcohol). If 30% of the methanol is turned into formaldehyde, the amount of formaldehyde is 18 times the USA EPA limit for daily formaldehyde in drinking water, 2 mg in 2 L water.

Aspartame (NutraSweet, Equal, Canderel, E951), after eight years of controversy, was suddenly and capriciously approved by a new FDA commissioner, Arthur Hull Hayes, Jr, just appointed by President Reagan, a pharmacologist who had been in office less than three months and had little background in food additives, in July 1981, overturning the vote of his own Scientific Board of Inquiry.

Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%), both ordinary amino acids, bound loosely together by methanol (wood alcohol, 11%). The readily released methanol from aspartame is within hours turned by the liver into formaldehyde and then formic acid, both potent, cumulative toxins.

A team in a Searle Co. lab, led by J.A. Oppermann, proved that 30% of the methanol in aspartame fed to rats remained, indubitably as toxic products of formaldehyde and formic acid in all tissues (1973, 1976).
Aspartame puts formaldehyde adducts into tissues, Part 1/2 full text, Trocho & Alemany 1998.06.26: Murray 2002.12.22

This was confirmed by an expert team at the University of Barcelona (Trocho, Alemany et al, 1998):
"...the binding of methanol-derived carbon to tissue proteins was widespread, affecting all systems, fully reaching even sensitive targets such as the brain and retina...These are indeed extremely high levels for adducts of formaldehyde, a substance responsible for chronic deleterious effects (33), that has also been considered carcinogenic (33,47)."
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation carcinogenicity results Dec 2002: Soffritti: Murray 2003.08.03

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal tract to become free methyl alcohol, which is metabolized in the liver to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level methanol exposure. CIIT Act. 14: 1-7.
Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats. M. Soffritti et al. Cancer Research Center, European Ramazzini Foundation for Oncology and Environmental Sciences, Bologna, Italy.
Eight depressed people react strongly to aspartame, Prof. Ralph G. Walton, MD, 1993 double-blind study, full text: Murray 2004.04.26 Despite the very small number of subjects, the results were dramatic and statistically significant. The eight depressed patients reported with aspartame, compared to placebo, much higher levels of nervousness, trouble remembering, nausea, depression, temper, and malaise.

Many scientific studies and case histories report:

* headaches * many body and joint pains (or burning, tingling, tremors, twitching, spasms, cramps, stiffness, numbness, difficulty swallowing) * fever, fatigue, swollen glands * "mind fog", "feel unreal", poor memory, confusion, anxiety, irritability, depression, mania, insomnia, dizziness, slurred speech, sexual problems, poor vision, hearing (deafness, tinnitus), or taste * red face, itching, rashes, allergic dermatitis, hair loss, burning eyes or throat, dry eyes or mouth, mouth sores, burning tongue * obesity, bloating, edema, anorexia, poor appetite or excessive hunger or thirst * breathing problems, shortness of breath * nausea, diarrhea or constipation * coldness * sweating * racing heart, low or high blood pressure, erratic blood sugar levels * hypothryroidism or hyperthyroidism * seizures * birth defects * brain cancers * addiction * aggrivates diabetes, autism, allergies, lupus, ADHD, fibromyalgia, chronic fatigue syndrome, multiple chemical sensitivity, multiple sclerosis, pseudotumor cerebri and interstitial cystitis (bladder pain).
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval: Turner: Murray 2002.12.23
Mark Gold exhaustively critiques European Commission Scientific Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references
Genotoxicity of aspartame in human lymphocytes 2004.07.29 full plain text, Rencuzogullari E et al, Cukurova University, Adana, Turkey 2004 Aug: Murray 2004.11.06
Murray, full plain text & critique: chronic aspartame in rats affects memory, brain cholinergic receptors, and brain chemistry, Christian B, McConnaughey M et al, 2004 May: 2004.06.05
Eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV Belsito, Nov 2003: Murray 2004.03.30
Continuing aspartame debate in British Medical Journal, John Biffra, Bob Dowling, Nick Finer, Ian J Gordon: Murray 2005.02.09
Politicians and celebrities hooked on diet sodas (aspartame): Murray 2004.03.24 gives 585,000 websites for "aspartame" , with the top 7 of 10 listings being anti-aspartame, while lists 786 aspartame items. ************************************************************

Additional material:
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999: Murray 2002.05.30
RTM: Smith, Terpening, Schmidt, Gums:
Full text: aspartame, MSG, fibromyalgia 2002.01.17
Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums Relief of Fibromyalgia Symptoms Following Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706. Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.

BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is often difficult to treat effectively.

CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome for two to 17 years are described. All had undergone multiple treatment modalities with limited success. All had complete, or nearly complete, resolution of their symptoms within months after eliminating monosodium glutamate (MSG) or MSG plus aspartame from their diet. All patients were women with multiple comorbidities prior to elimination of MSG. All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD Asst. Clinical Prof. Community Health and Family Medicine, U. Florida, Gainesville, FL Shands Hospital West Oak Clinic Gainesville, FL 32608-3629 352-376-5071
Formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA: Gold: Wilson: CIIN: Murray 2002.12.12

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.
Sam-1 Trust, Alto, New Mexico, USA. Full text
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
Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde adducts in rats: Murray 2002.09.08 rmforall Prof. Alemany vigorously affirms the validity of the Trocho study against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review available for $35, [an industry paid organ]. Butchko
"When all the research on aspartame, including evaluations in both the premarketing and postmarketing periods, is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use."

In the same report, Schiffman concludes on page S49, not citing any research after 1997, "Thus, the weight of the scientific evidence indicates that aspartame does not cause headache." Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University 919-684-3303, 660-5657
RTP ties to industry criticized by CSPI: Murray: 2002.12.09
Aspartame in Merck Maxalt-MLT worsens migraine, AstraZeneca Zomig, Eli Lilly Zyprexa, J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab, Pfizer Cool Mint Listerine Pocketpaks: Murray 2002.07.16

Migraine MLT-Down: an unusual presentation of migraine in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame, while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research
Blumenthall & Vance: aspartame chewing gum headaches Nov 1997: Murray 2002.07.28

Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches. Headache 1997 Nov-Dec; 37(10): 665-6. Department of Neurology, University of Oklahoma College of Medicine, Tulsa, USA.
Aspartame, a popular dietetic sweetener, may provoke headache in some susceptible individuals. Herein, we describe three cases of young women with migraine who reported their headaches could be provoked by chewing gum sweetened with aspartame. [ 6-8 mg aspartame per stick chewing gum ]

Finally, an intripid and much published team in Japan has found DNA damage in 8 tissues from single non-lethal doses of aspartame (near-significant high levels of DNA damage in 5 tissues) and many other additives in groups of just 4 mice:

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

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

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

Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg).

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

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

Based on these results, we believe that more extensive assessment of food additives in current use is warranted. PMID: 12160896
24 recent formaldehyde toxicity [Comet assay] reports: Murray 2002.12.31
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in mice: Sasaki YF & Tsuda S Aug 2002: Murray 2003.01.01 [ 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.]
Genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor; sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002: Murray 2003.01.27 [A detailed look at the data] ] original documents and long reviews of flaws in aspartame toxicity research: Murray 2002.07.31
Samuels: Strong: Roberts: Gold: flaws in double-blind studies re aspartame and MSG toxicity: Murray 2002.08.01

"Survey of aspartame studies: correlation of outcome and funding sources," 1998, unpublished:
Walton found 166 separate published studies in the peer reviewed medical literature, which had relevance for questions of human safety. The 74 studies funded by industry all (100%) attested to aspartame's safety, whereas of the 92 non-industry funded studies, 84 (91%) identified a problem. Six of the seven non-industry funded studies that were favorable to aspartame safety were from the FDA, which has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio Universities, College of Medicine, Dept. of Psychiatry, Youngstown, OH 44501, Chairman, The Center for Behavioral Medicine, Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown, OH 44501 330-740-3621
Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity: Murray 2001.06.04 Four double-blind studies

Headache 1988 Feb; 28(1):
10-4 The effect of aspartame on migraine headache.
Koehler SM, Glaros A PMID: 3277925, UI: 88138777
Shirley M. Koehler, PhD 904-858-7651
Alan Glaros 816-235-2074

They conducted a double-blind study of patients, ages 18-55, who had a medical diagnosis of classical migraines (normally having 1-3 migraines in 4-weeks), who were not on medications (other than analgesics), and who suspected that aspartame had a negative effect on their migraine headaches. The subjects were given 1200 mg daily, aspartame or placebo, for four weeks, about 17 mg/kg. The placebo group had no increase in headaches. Approximately half of the subjects (5 of 11) who took aspartame had a large, statistically significant (p = 0.02), increase in migraine headache frequency, but not in intensity or duration, compared to baseline or placebo. Only 11 of 25 subjects completed the program: 8 dropped out, 4 began new medications, 2 had incomplete records. They were at home. Since 1/3 of the subjects dropped out, they may have been choosing to avoid headaches-- were they unpaid? To achieve statistical signifance with only 11 subjects hints that the incidence rate from aspartame is very high, about 1/2, for migraine cases who believe that they are hurt by aspartame.
Eight depressed people react strongly to aspartame, Prof. Ralph G. Walton, MD, 1993 double-blind study, full text: Murray 2004.04.26

Walton, RG, "Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population," 1993, with Robert Hudak and Ruth J. Green-Waite, Biological Psychiatry, 34 (1), 13-17.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio Universities, College of Medicine, Dept. of Psychiatry, Youngstown, OH 44501, Chairman, The Center for Behavioral Medicine, Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown, OH 44501 330-740-3621

Eight depressed patients, ages 24-60, and five non-depressed controls, ages 24-56, employed at the hospital, were given for 7 days either aspartame or a placebo, and then after a 3 day break, given the opposite. Each got 2100 mg aspartame daily, 30 mg/kg bodyweight, equal to 10-12 cans of diet soda daily, about a gallon. Despite the very small number of subjects, the results were dramatic and statistically significant. The eight depressed patients reported with aspartame, compared to placebo, much higher levels of nervousness, trouble remembering, nausea, depression, temper, and malaise. (For each symptom, p<0.01) The five normals did not report strong enough differences between aspartame and placebo to be significant. Initially, the study was to be on a group of 40, but was halted by the Institutional Review Board because of severe reactions among 3 of the depressed patients.

Again, statistical significance with only 8 depressed patients: "In this study, patients most often began to report significant symptoms after day 2 or 3." The incidence rate is very high, indeed, about 1/3. The most common symptoms are entirely typical of thousands of case histories.

Stephen K. Van Den Eeden, T.D. Koepsell, W.T. Longstreth, Jr, G. van Belle, J.R. Daling, B. McKnight, "Aspartame ingestion and headaches: a randomized crossover trial," 1994, Neurology, 44, 1787-93 Steven K. Van Den Eeden,PhD 550-450-2202 Division of Research, Kaiser Permanente Medical Care Program 3505 Broadway, Oakland, CA 94611-5714

In their introduction, they comment:

"In addition, the FDA had received over 5,000 complaints as of July, 1991 in a passive surveillance system to monitor adverse side effects. (17) Neurologic problems constitute the primary complaints in these and several other case series, with headaches accounting for 18 to 45 %, depending on the case series reported. (17-19)"

Subjects, ages 18-57, were recruited who believed they got headaches from aspartame, but were otherwise mentally and physically healthy. They were paid $ 15 total, and were at home. Of the 44 subjects, 32 contributed data to the 38-day trials: a week of inert placebo, a week of either aspartame or placebo, followed by a week of the opposite, and then this two-week cycle repeated. The daily dose was about 30 mg/kg. "The proportion of days subjects reported having a headache was higher during aspartame treatment compared with placebo treatment (aspartame = 0.33, placebo = 0.24; p = 0.04) (table 5)". Of the 12 subjects not included in the data, 7 reported adverse symptoms before withdrawing.

Again, statistical significance with a moderate number of healthy subjects, willing to be recruited by a newspaper ad, who believed aspartame hurt them. The number of headaches for each subject for each treatment week are given: it appears that 4 subjects had the strongest increase in headaches from the run-in week or placebo week to their first week on aspartame, jumping from 0 to 5, 1 to 6, 1 to 4, 0 to 5 headaches per week. So, about 4 of the 44 healthy people recruited for the study, who believed aspartame hurt them, had a strong increase in headaches from the first week of daily aspartame exposure, while 7 reported adverse symptoms before leaving, a total of 11 out of 44, an incidence ratio of 1/4.

This is sky high, if we consider that, if the incidence ratio for the about two hundred million users in the USA is 1 of 100, that is 2 million cases. It is plausible that the incidence ratio lies between 1 and 10 out of 100 for continuous daily exposure. These three flames should have set off alarm bells, with extensive follow-up studies and much more careful study of thousands of case histories. But these little flares were adroitly smothered by thick blankets of industry funded fluff:
Simmons: Gold: Schiffman: Spiers: aspartame toxicity: Murray 2001.06.04 Two double-blind studies