Mark Gold
Aspartame Toxicity Center

Posted: 18 September 2008

This article was originally posted at:

In 2007, a review of aspartame entitled, "Aspartame: A Safety Evaluation Based on Current Levels, Regulations, and Toxicological and Epidemiological Studies" was published in the scientific journal, "Critical Reviews in Toxiology" (Magnuson 2007). Shortly after the publication, a flurry of press releases proclaimed:

"A new review of aspartame research -- the most comprehensive ever conducted -- once again has concluded the widely used sugar substitute is safe, even among its heaviest users."


"International Scientists Conclude Sweetener Is Safe Across Population Groups."

What these press releases did not tell readers is that this review was funded by the aspartame manufacturer, the authors had serious conflicts of interests, and in page after page after page of the review, research was misrepresented and important research and information was omitted from the review. This analysis is intended to help readers understand how manufactures pay for and get published reviews that put their toxic products in a positive light.

A. Conflicts of Interest

The review was funded by Ajinomoto of Japan. Ajinomoto along with Monsanto have been the world's biggest producers and sellers of aspartame. The authors of the review had numerous, obvious conflicts of interests as described below. Yet this information was apparently not disclosed to the journal it was published in. The parent company of the journal stated in a press release that, "There were no known conflicts of interest with the sponsor or potential biases of the authors" (Informa 2007).

Gary M. Williams was the Chairman of the American Health Foundation (AHF) which was funded in part by The NutraSweet Company and other companies selling aspartame-containing products (Williams 1987). AHF Board of Directors have included representatives of PepsiCo and the National Soft Drink Association (CSPI 2003). The AHF received more than $163,000 in grants from Philip Morris. "Regarding an AHF press kit prepared by the PR firm, Ruder and Finn, William Ruder writes to Philip Morris: 'please note that we have handled it so that there is not one single mention of the problem of smoking and health.'" (CSPI 2003, Ruder 1975). In 1987, the American Health Foundation (AHF) convened a conference, Sweeteners: Health Effects where an AHF representative concluded that aspartame and other sweeteners were safe: "It is clear from the perspective of potential cancer risk that the sweeteners described in some detail in this report are safe and wholesome, and perhaps more so, than sugar. As we noted, it is our hope that this workshop will be the basis for international recognition of this fact, so that medical research effects can be directed effectively to areas more relevant to health maintenance." (Weisburger 1987)

Two of the authors, Robert Kroes and Gary M. Williams joined with Ian C. Munro, the president of the Cantox Health Sciences International corporate advocacy group, to work with Monsanto to review its herbicide, glyphosate (Williams 2000). The work of these authors, directly with Monsanto, was not disclosed in this aspartame review.

Cantox (now known as Intrinsik) specializes "in assisting clients in their efforts to develop, gain regulatory approval and market products nationally or internationally." Cantox is famous as a corporate advocacy group for whitewashing the dangers of Agent Orange, another toxic product created by Monsanto (Dominion 2007). In 2002, the president of Cantox, Ian C. Munro (see above), worked directly with NutraSweet company employees and consultants on an aspartame review where he stated: "After 30 plus years of rigorous scientific research, it is time to put questions of aspartame safety to rest. ... The continuing debate over such a 'nonissue' only serves to divert attention and the allocation of resources from more important health issues that need to be addressed." (Butchko 2002).

Bernadene Magnuson, the lead author of this review was also the Senior Scientific and Regulatory Consultant for Cantox Health Sciences International, a corporate advocacy group mentioned above (UT 2008). The president of Cantox had already called aspartame toxicity a "nonissue," yet the lead author of this review worked for Cantox!

Bernadene Magnuson became a member of the corporate advocacy group, The Burdock Group in 2005. (Nutra 2005). The Burdock Group offers its clients "technically rigorous, comprehensive safety and regulatory management of their products. .... The Burdock Group offers the highest quality consulting services for the safety and regulatory issues facing the Food and Beverage, Dietary Supplement, Cosmetics/ Personal Care and Pet Food Industries. Together, we form a cohesive team that offers single-source solutions for your business's safety assessment and regulatory needs." (Burdock 2008). This author's work for pro-aspartame advocacy group, Cantox and corporate advocacy group, Burdock Group was not disclosed in this aspartame review.

Gary Marsh has had researched funded by the Formaldehyde Institute, a trade association consisting of Monsanto, Dupont and other chemical companies (CSPI 2008a, Tataryn 1983). The Formaldehyde Institute raised money for research in an attempt to portray formaldehyde exposure in a good light. Since independent published research has shown that aspartame ingestion leads to formaldehyde accumulation in the brain, kidneys, liver and other organs and tissues (Trocho 1998), Gary Marsh's research for the Formaldehyde Institute is a serious conflict of interest. This author's funding from the Monsanto-supported Formaldehyde Institute was not disclosed in this aspartame review.

Michael Pariza was a scientific advisor to the industry-funded advocacy group, "American Council on Science & Health" (ACSH) (CSPI 2008a). According to an article in the Washington Post:

"In 1982, the American Council on Science and Health ( ACSH ) filed a friend-of-the-court brief in a Formaldehyde Institute lawsuit that overturned a federal ban on formaldehyde insulation. .... At least a third of ACSH 's funding comes from such companies as Allied Corp., Coca-Cola, the National Soft Drink Association, Colgate-Palmolive Co., Dow Chemical Canada, du Pont, Eli Lilly, Exxon, General Mills, General Foods Fund, Gulf Oil, Hershey Foods, Johnson & Johnson, Kellogg's, Monsanto Fund, Mobil Foundation, M&M/Mars, Pillsbury Foundation, Procter & Gamble, Pfizer, Shell Oil, Upjohn and Velsicol Chemical." (Kurtz 1984).

Michael Pariza is also a member of the Board of Trustees of the International Life Sciences Institute (ILSI), a chemical and food company research association funded by Ajinomoto, Monsanto, Coca Cola, PepsiCo, Nestle, and many other food and chemical companies involved in the production, use and sale of aspartame (Nutrition 2003, CSPI 2008b, ILSI 2005). This author's official positions within industry associations funded by Ajinomoto and Monsanto were not disclosed in this aspartame review.

Ronald Walker spent seven (7) years as the ILSI's Chairman of their Scientific Committee on Toxicology/Food Safety in Europe (Walker 2001). As mentioned above, ILSI is funded by Monsanto, Ajinomoto, Coca Cola, Pepsi Cola, etc. He was a consultant for DSM Nutritional Products, a company that sold "Twinsweet" from Holland Sweetener Company which is a mixture of aspartame and acesulfame-k. The DSM web site contained aspartame advocacy articles written by Holland Sweetener Company (Walker 2007, DSM 2008). He was a consultant Numico Beheer BV / Danone Group, a company that had a joint venture with Ajinomoto (the sponsor of this review) (Walker 2007, Asia 2007). He is a paid consultant to the corporate public relations group, the European Food Information Council with corporate members that include Coca Cola, PepsiCo, Danone, Nestle, etc. (Walker 2007, EUFIC 2008). Finally, he was a paid consultant for Cantox Health Sciences International (Walker 2005).

Ronald Walker wrote a glowing review of another Ajinomoto product, monosodium glutamate (MSG) for a symposium funded by an Ajinomoto managed trade group, International Glutamate Technical Committee (IGTC) (Walker 2000, Ishii 2003). He has participated in another aspartame review where he claimed that aspartame was safe (SCF 2002). This author's funding from companies selling aspartame, official positions with associations who are supported by aspartame manufacturers and marketers as well as his past positions defending aspartame was not disclosed in this aspartame review.

John Doull was a paid consultant of Monsanto, a member of the Monsanto-funded ACSH Advisory Board, and a Trustee of the Monsanto- and Ajinomoto-funded corporate research association, ILSI (Tobacco 1993, CSPI 2008). This author's consultancy with Monsanto and official positional within Monsanto- and Ajinomoto- funded associations was not disclosed in this aspartame review.

A reader might ask, "Is it possible for there to be an unbiased review of aspartame, made by Ajinomoto and Monsanto, where the review is funded by Ajinomoto, authors have done paid work for Monsanto, several authors have offical positions in trade and research associations funded by Monsanto, Ajinomoto, Coca Cola, PepsiCo, etc., several authors work for corporate advocacy groups, one of which called aspartame toxicity a 'nonissue,' and one author who consults for companies that sell aspartame and in the past has said that aspartame is safe?" I think a reasonable answer might be, "No! Are you kidding me?!"

B. Misrepresenting the Research

It is extremely common for "Reviews" funded by manufacturers of unhealthy or toxic products to misrepresent the research so as to promote their products amongst medical professionals. However, it is becoming more common for manufacturers and trade associations to use corporate advocacy groups to hand-pick researchers to misrepresent the research for them. Not only do these reviews contribute to continued exposure of the general public to toxic products like aspartame, but some medical professionals, who do not have the time to check all references for accuracy, are duped into thinking a toxic product is safe. This section is intended to use examples from this aspartame review to demonstrate how medical professionals can be misled when research is misrepresented and key research and information is omitted.

B.1. Formaldehyde Poisoning From Aspartame

An independent study in Europe demonstrated that aspartame ingestion at relatively small levels lead to the accumulation of formaldehyde adducts (bound to protein) in the liver, kidneys, brain, and other organs and tissues (Trocho 1997). This published, peer-reviewed, independent study was not even mentioned in this review! One of the techniques for misrepresenting research is to avoid mentioning the research altogether!

Some of the side effects of chronic formaldehyde poisoning include:

- Irreversible genetic damage from long-term, low-level exposure (Shaham 1996)
- Headaches, fatigue, chest tightness (Main 1983)
- Sleeping problems, burning skin, fatigue, chest pain, dizziness (Liu 1991)
- Headaches, fatigue, IgE-mediated sensitization (Wantke 1996)
- Musculoskeletal, gastrointestinal, and cardiovascular symptoms (Srivastava 1992)
- Headaches, tiredness (Olsen 1982)
- Headaches, dizziness, nausea, lack of concentration ability (Burdach 1980)
- Cytogenic effects of blood lymphocytes (Suruda 1993)
- Fertility (adverse effects) (Taskinen 1999)
- Cognitive adverse effects (Kilburn 2000)
- Seizures and neurobehavioral impairment (Kilburn 1994)
- Headaches, skin problems (Proietti 2002)
- Low birth weight (Maroziene 2002)
- Neurobehavioral symptoms (Kilburn 1985)
- Memory problems, equilibrium and dexterity impairment.(Kilburn 1987)

Methanol is quickly absorbed from aspartame ingestion (Davoli 1986). Methanol is converted into formaldehyde in the body (Kavet 1990). Some of the formaldehyde is converted into formic acid and eliminated by the body (Kavet 1990). However, Trocho (1998) demonstrated that aspartame ingestion at low levels by rodents: 20 mg/kg body weight (acute dose) or 200 mg/kg body weight (chronic dose), lead to formaldehyde accumulation in the liver, brain, kidneys and other parts of the body. The formaldehyde was bound as "adducts" to proteins and DNA. Research in humans demonstrates that adduct formation can occur from formaldehyde exposure (Carraro 1997, 1999).

Another way the reviewers can convince medical professionals that chronic formaldehyde poisoning from aspartame is not a problem is to convince them that the methanol obtained from aspartame (and then converted into formaldehyde in the body) does not increase methanol levels in the blood plasma.

Table 25 on page 692 of the Magnuson (2007) review purports to show several studies where plasma methanol levels did not rise except for when very large doses of aspartame were ingested (Stegink 1981, Stegink 1983, Stegink 1989). What they don't tell you, but what can be seen by reading the research is that these industry-sponsored studies used an extremely old methanol measuring technique from 1969 (Baker 1969) that would not be able to see any plasma methanol increases until it went up by 500 - 600% ! Relatively small amounts of aspartame can cause a doubling of plasma methanol levels (Davoli 1986). Legitimate researchers use plasma methanol measuring techniques that are not worthless (e.g., d'Alessandro 1994, Osterloh 1996, Cook 1991). The fact that the Magnuson (2007) reviewers did not mention any of these issues proves that they are either not familiar with the research or would knowingly keep crucial information from readers.

Another way for the reviewers to convince readers that the methanol from aspartame converting into formaldehyde and accumulating is not a problem is to compare the methanol levels in aspartame to that in fruits and other products. The reviewers state: "Similarly, Butchko and Kotsonis (1991) estimated that tomato juice provides about six times as much methanol as an equivalent volume of an aspartame- sweetened beverage. .... In conclusion, the amount of methanol contributed to the diet from aspartame-containing products consumption is likely to be less than that from natural sources."

This argument put forth by the reviewers was largely addressed in an independent review in 1984 by Dr. Woodrow Monte entitled, "Aspartame: Methanol and the Public Health" (Monte 1984). The manufacturer was concerned enough about the debunking of their argument related to aspartame, methanol and fruit that they wrote a Letter to the Editor in 1985 attempting to address Dr. Monte's arguments (Sturtevant 1985). However, these reviewers avoided citing Dr. Monte's review and even the manufacturer's response from 1985.

Dr. Monte pointed out that there are "protective factors" in traditionally-ingested foods/drinks that contain methanol. For example, wine has high levels of methanol, but it also has high levels of ethanol. The ethanol blocks the conversion of methanol into formaldehyde so that the methanol can safely be eliminated in the urine and breath (Leaf 1952, Liesivuori 1991, Roe 1982). Fruits also have protective factors to prevent the conversion of methanol into formaldehyde as detailed by Dr. Monte and as detailed in my heavily-referenced article entitled, "Scientific Abuse in Methanol / Formaldehyde Research Related to Aspartame," available at:

By not mentioning independent, published research that is well known to the manufacturer and debunks some of the manufacturer's arguments related to aspartame, methanol and formaldehyde, these reviewers once again show either their bias and/or lack of knowledge of the scientific literature as it relates to aspartame.

The reviewers recite numerous other arguments put forth in the past by the manufacturer. All of these arguments have been addressed in detail in the scientific literature and on the following web page:

B.2. Aspartame and Seizures

Section of the Magnuson (2007) review entitled, "Effect of Aspartame on Seizures" on page 696 cited two industry-funded, double-blind studies (Shaywitz 1994, Rowan 1995). The way these studies are presented, the reader gets the sense that a large amount of aspartame will not cause seizures, even in persons who are predisposed to seizures.

What they didn't tell the readers is that nearly all of the subjects in these two aspartame industry-sponsored studies were taking anti-seizure medication during the study! It is obvious that anti-seizure medication can help prevent seizures.

But the Magnuson (2007) reviewers presented these studies as if they had relevence to the overwhelming majority of people who do not take anti-seizure medication. Either they didn't read the studies they're reviewing or they knowingly left crucial information out of their review.

In addition, the reviewers left out information that the aspartame used in these studies are, according to industry consultants, not "bioequivalent" to aspartame taken in real-world products (Stegink 1987a). The aspartame was given in slow-dissolving capsules. Giving aspartame in slow-dissolving capsules tremendously-reduces the biochemical changes that normally occur from real-world aspartame ingestion. The methanol absorption is slowed tremendously, allowing the body to eliminate more of it before it is transformed into formaldehyde. The absorption of the excitotoxic amino acid is slowed so that the liver can prevent the sudden spike in plasma levels of this amino acid normally seen when aspartame is ingested in liquids (Stegink 1987a, 1987b).

Finally, the reviewers showed no concern that these industry studies were one day (Rowan 1995) and two weeks long (Shaywitz 1994). Roberts (1988) looked at 551 cases of reported aspartame toxicity. He showed that reactions to aspartame appeared anywhere from immediately to more than one (1) year after initial use began. Keeping the studies short helped guarantee that there would be few, if any, adverse reactions. According to a NutraSweet Company representative, the two week Shaywitz (1994) study was to be conducted on 20 subjects (Kotsonis 1987), yet only 10 subjects were described in the publication. The reviewers did not question what happened to the other 10 subjects.

B.3. Aspartame and Vulnerable Populations

On page 695 the reviewers state:

"Concerns exist that the only studies done that show no effect of aspartame are those which use healthy adults and people used to high intakes of aspartame such as diabetics and people on weight-loss regimes (Tsakiris et al., 2006). However, the effect of acute high-dose aspartame was also evaluated in a double- blinded study of 18 patients with Parkinson's disease, as this was considered a susceptible target population for adverse effects (Karstaedt and Pincus, 1993)."

Here again, industry-sponsored studies on aspartame tend to be very short, especially in susceptible population groups. This study on Parkinson's patients was less than one day long! The study purported to test whether the increase in plasma phenylalanine levels effects other measurable health-related parameters. However, since they gave the aspartame in slow-dissolving capsules, there was only a relatively small increase in plasma phenylalanine levels.

Do these reviewers actually think that one day studies for testing a chronic poison on a vulnerable population is appropriate? Apparently so, because they had absolutely no criticism of this and other similar industry-sponsored studies.

B.4. Aspartame and Medium-Term Research

The Magnuson (2007) review described an industry-sponsored study by Leon (1989) where aspartame or placebo was given to healthy adults for 24 weeks:

"The results indicated no differences between groups in body weight, vital signs blood lipid levels, urinalysis results or incidence of complaints...."

What the reviewers didn't mention is that there were approximately 50% more adverse reactions in the aspartame group than in the placebo group. However, the researchers split the reactions in 14 smaller subcategories and they could then claim that within each tiny subcategory, there was no "statistically significant" increase in aspartame reactions.

B.5. Aspartame and Migraines / Headaches

When the Magnuson (2007) reviewers discuss aspartame and headaches, they were critical of two reletively long, independent studies linking aspartame use to headaches or migraines (Koehler 1988, Van Den Eeden 1994), but had not a single criticism on an aspartame industry-sponsored study that found no link between aspartame and headaches (Schiffman 1987).

Again, these reviewers had not one criticism of the industry-sponsored Schiffman (1987) study even though it was only one day long. While the Koehler (1988) study was four weeks long and the Van Den Eeden (1994) study was 14 days long. The reviewers also neglected to point out that in the Schiffman (1987) study, 77.5% of the subjects taking the placebo experienced adverse reactions during the one-day period! 45% of the subjects taking the placebo experienced headaches. This is a ridiculously high percentage of subjects reporting adverse reactions to "placebo" in a single day. The number of participants used in this study was "sufficient to ensure that a difference of 33% in the incidence rates of headache" between the aspartame and placebo control groups would be seen as statistically significant. This means that if less than 78% (45% + 33%) of the persons taking aspartame reported headache reactions, it would not be considered statistically significant.

Magnuson (2007) did not even mention the critque of the Schiffman (1987) study by the Editor of the journal, Headache (Edmeads, 1988), nor did they mention other published criticisms:

"Unfortunately, their experimental design was flawed in such a way that their negative results in no way support their conclusion that 'aspartame is no more likely to produce headache than placebo.'" (Elsas 1988)

"We believe that the study of Schiffman et al had some serious flaws and did not reflect the realities of migraine due to dietary factors." .... "Persons susceptible to migraine and other vascular headaches should continue to be warned of the possible aggravating role of aspartame." (Steinmetzer 1988)

B.6. Aspartame and Aspartic Acid

On page 691 of the Magnuson (2007) review, they state:

"...there have been no observed adverse effects of large doses of aspartic acid in studies with humans (see reviews: Meldrum, 1993; Institute of Medicine, 2005) or nonhuman primates (Reynolds et al., 1976, 1980)."

What they don't say is: 1) there have been no long-term studies on human subjects given free-form (unbound-to-protein) aspartic acid; 2) the concerns related to acute effects of aspartic acid involve potential irreversible damage to parts of the brain of infants and young children who are exposed to high levels of free-form aspartic acid from aspartame. These effects have been seen in infant and young animals. 3) Industry studies claiming no effect of excitotoxins such as aspartic acid on non-human primates gave brain-protected drugs to the animals and used a recroped picture from an earlier and different study to claim no effects (Olney 1993). As described by Dr. John W. Olney:

"In addition, the 2nd report by Reynolds, Filer and colleagues (Stegink 1975), admitted for the first time that their monkeys were maintained under Sernylan (phencyclidine) anesthesia throughout the 6 hr experiment. Failure to divulge in their 1st report that their animals were anesthetized with phencyclidine is a particularly critical omission, since the use of phencyclidine thoroughly invalidates the entire study in the eyes of any knowledgable neuroscientist. Phencyclidine is one of the most potent antagonists of glutamate receptors known (Wang 1990, Olney 1990, Olney 1986). Administration of phencyclidine or its various analogs, such as MK-801, totally prevents glutamate (even very high doses of glutamate) from damaging the hypothalamus (Wang 1990). Not only does the use of phencyclidine totally invalidate the primate non-susceptibility claims of Reynolds et al., their deliberate representation that 'No unusual behavior was exhibited by the infants' when they clearly were aware that their infant monkeys had actually been drugged and anesthetized, raises additional grave questions."...

"In 1976, Reynolds et al attempted to convince the world definitively that glutamate is non- toxic for the infant primate by publishing a 3rd report (Reynolds 1976) in which new evidence is presented on an additional specie of monkey (fascicularis, a specie not documented in their first 2 reports). This report is illustrated with a brain section from a 7 day old fascicularis monkey that ingested glutamate 5 hrs earlier (Appendix, Exhibit # 2). Incredibly, the brain section used to illustrate the new finding is the same brain section used in their second report (Stegink 1975) to illustrate lack of brain damage in a 1 day old rhesus monkey dosed with glutamate 6 hrs earlier ( Appendix, Exhibit #2). These illustrations are obviously spurious for two reasons: 1) They cannot possibly constitute evidence from two separate monkeys or two separate species because they are one and the same photograph which has merely been cropped differently during photographic printer; 2) Regardless how this photograph is cropped, it does not authentically document lack of glutamate toxicity because it is selected from the caudal level of the hypothalamus which lies outside the zone that is subject to damage by orally administered glutamate. When Dr. Reynolds published this spurious photograph in her 3rd paper (Reynolds 1976), she had very good reason to know that it was from the wrong region of the brain, because not only had I instructed her colleague and co-author on this matter in 1972, but I met with Dr. Reynolds herself in 1975 and briefed her very carefully and pointedly on both the science and the ethics of this matter. This briefing was one year prior to the publication of her 3rd spuriously documented report."

C. Conclusion

Nearly every section of the Magnuson (2007) review has research that is misrepresented and/or crucial pieces of information are left out. In addition to the misrepresentation of the research, readers (including medical professionals) are often not told that this review was funded by the aspartame manufacturer, Ajinomoto, and the reviewers had enormous conflicts of interest.

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