Quick Review of Monsanto/NutraSweet's PR Statments Regarding the Aspartame / Brain Cancer Research Published by Dr. John W. Olney, et al. in the Journal of Neuropathology and Experimental Neurology (Nov. 1996) by Mark Gold mgold@holisticmed.com http://www.holisticmed.com/aspartame/ (See web page for more information and sweetener resources.) Dr. Dimitrio Trichopoulos ------------------------- According the "The Observer" of London, Dr. Trichopoulos was approached by the manufacturer, Monsanto/NutraSweet, to write a critique of the study for them. Therefore, his statements are obviously not the statements of an independent scientist. > "This paper has a misleading title. The 'Results' section which, as > a rule, addresses the original contribution of the paper, does not > even include the word 'aspartame' that nevertheless figures > prominently in the title and the running title." The title of the paper is: "Increasing Brian Tumor Rates: Is There a Link to Aspartame?" The title is clearly intended to show that the paper examines the increasing brain tumors rates and tries to determine if aspartame is a possible cause. It is hardly misleading. The "Results" section is the results of the analysis of the rates of various types of brain tumors. The "Discussion" section is used to discuss whether aspartame may play a part in the increasing rates of certain types of brain tumors. Such comments are really silly and have no place in a serious discussion of the aspartame / brain cancer link. > "Instead, the paper examines time trends of brain tumor incidence and > mortality in the United States, as many other authors have > previously done, with a twist that is methodologically so unsound as > to make the conclusions of the paper clearly untenable." Given that Dr. Trichopoulos was reviewing this study at the request of the manufacturer, it may not surprise some that he made this comment. However, this statement contains no discussion of why the methodology was unsound -- it is just the opinion of someone reviewing the study for the industry. > "Therefore, the arguments presented by Olney et al. fly in the face > of the ecological evidence that they invoke. The introduction and > widespread use of aspartame coincides in time with a *deceleration of > an increasing trend that has been apparent well before aspartame was > introduced. No one could seriously claim that this deceleration is > due to aspartame, but the sugestion that aspartame causes brain > cancer on the basis of these data is even more preposterous." A common trick of aspartame industry PR is to argue against a point that no one (including Dr. Olney) is trying to make. The above comment is looking at the *overall* brain cancer incidence rates over the past 15-20 years. It is clear that brain cancer incidence rates have been climbing rapidly since the 1970s. Dr. Trichopoulos may be correct that *overall* brain cancer incidence rates are not increasing quite as rapidly as they did before aspartame was approved. However, all of this seems to have little to do with Dr. Olney's research. Dr. Olney points out that it is the rates of the extremely deadly forms of brain cancer (e.g., glioblastoma and anaplastic astrocytoma) in the most susceptible populations that went up significantly not long after aspartame's approval. The rates of the much less deadly brain cancer (i.e., astrocytoma) went down not long after aspartame approval. It is the increase in the rate of conversion of astrocytic tumors from a lower to higher grade (i.e., more deadly) that Dr. Olney, et al. focused on, not simply the change in overall brain tumor rates. >"The arguments of Olney et al. implicitly require two biologically >indefensible assumptions: that a certain factor (aspartame) could >cause a solid tumor (brain cancer) with a latency period of less than >four years and that subsequent widespread exposure to this factor >would cause no further increase in the incidence of that cancer. >These assumptions are preconditions in their futile effort to >explain, in causal terms, an arbitrarily chosen and improperly >illustrated transient shift in the secular incidence of brain >tumors." As you can see, Dr. Trichopoulos once again seems to avoid discussing the large shift of brain tumor rates to much more deadly forms of brain tumors. He seems set on discussion overall brain cancer rates despite the fact that it is only briefly discussed in Dr. Olney's paper. Dr. Olney quite clearly expresses in the "Method" section of the paper that he will be discussing specific tumor types in relation to aspartame: "In prior studies, the focus has been primarily on total tumor incidence without adequate attention to individual tumor types, and there has been a tendency to assess the magnitude of overall change in incidence from one extreme time point to another (e.g., from the early 1970s to the mid 1980s) without determining whether the increases occurred episodically or on a steadily progressive basis. Because increases attributable to aspartame would be expected to have a unique temporal pattern corresponding to the pattern of public exposure to this agent, and might be limited to increases in only specific tumor types, we plotted the incidence rate for each year and each tumor type from 1975 to 1992...." Dr. Olney points out that "it is currently believed that multiple separate mutations involving several types of proteins must occur to cause normal cells to become carcinogenic. Thus, in human adult or aging populations the accumulation of spontaneous mutations may be sufficient to set the stage for an environmental agent to provide a single critical factor required to trigger carcinogenesis." Therefore, in the population group that is, by far, the most susceptible to glioblastomas and anaplastic astrocytomas -- the late middle aged and elderly -- it would certainly be possible for brain tumors to progress after 4-5 years that aspartame was on the market. It is the less susceptible populations that would likely see a longer time period (on average) before the tumor develops. Dr. Paul Levy ------------- Dr. Levy has cowritten with Monsanto/NutraSweet a defense of aspartame (Neurology 45:1631). That, by itself, doesn't prove that Dr. Levy's statements are inaccurate, but it does show that Dr. Levy was not an independent researcher who happened to write comments about this study. > "...this statistical and epidemiological treatment of the SEER data > is seriously flawed and furnishes no evidence to justify the > conclusion of an association between aspartame use and increased > brain tumor incidence rates." Again, nothing but opinion. It is interesting that Monsanto/NutraSweet would approach their friends in the scientific community to comment on the study, but would quite often quote statements such as that above that have no facts or reasonining associated with them. We will just have to wait until the responses are published in the Journal of Neuropathology and Experimental Neurology before we see what (if anything) they are basing these statements on. > "When the same analysis is performed separately in age groups 0-19 > years, 20-39 years, 40-64 years, and 65 plus years, the only > significant increase with time is in the 65 plus age group which can > be explained, at least in part, by the increased access to health > care including diagnostic procedures among the elderly." Once again, it appears that Dr. Levy is now discussing *overall* brain tumor rates. Dr. Olney shows that the much more deadly types of brain cancer (glioblastoma and anaplastic astrocytoma) increased substantially in the 45-69 age group and the 70+ age group. As Dr. Olney stated, "the earlier onset of the highly malignant tumors in the older age groups could relate to the fact that they have had more years to accumulate spontaneous mutations for the proposed aspartame-linked mutations to interact with." If exposure of in utero fetuses to aspartame can cause brain tumors on a delayed basis, tumors induced by this mechanism may not become evident for another 20 or 30 years." Dr. Olney also discusses the effect of the changes in diagnostic procedures on cancer incidence rates. Here is an excerpt from Dr. Olney's paper that should help put to rest Dr. Levy's unsubstantiated statement about diagnostic precedures: "It is reasonable to question whether the steady increase in these tumors occuring in phase 2 [1985-1992] could be explained in terms of MRI (introduced circa 1983) being able to detect additional tumors not detectable by CT [technology]. We consider this unlikely for the following reasons: Sophisticated detection methods are not used for general screening, but rather for diagnosis of conditions that are producing clinical symptoms. Most if not all of these tumors are malignant enough so that when they begin to produce symptoms they are already large enough (or soon will be) to be detected by either MRI or CT. Certain occult, benign, very slow growing tumors (e.g., gangliogliomas) can be detected earlier and more effectively by MRI than CT, but the tumors in question would effectively be detected in a relatively short time by either technology." --------------- Dr. Adalbert Koestner --------------------- Dr. Koestner wrote a chapter about aspartame and brain tumors for the manufacturer's aspartame book in 1984. Once again, this shows that Dr. Koestner just didn't happen to read the study and respond as might an independent researcher. > "Dr. Olney states, 'The most striking fiding was that the 320 > aspartame-fed rats developed 12 malignant brain tumors and 120 > concurrent controls had not brain tumors.' This statement is a > misrepresentation of the facts." It amazes me that Dr. Koestner could question Dr. Olney's statements on this fact since Dr. Olney was an active participant in the pre-approval hearings when the number of tumors was discussed. It is clear that Dr. Koestner inappropriately received his tumor figures from UAREP, an organization that was reportedly paid $500,000 to "review" studies for the manufacturer. (See the footnote at the bottom of the second page of Dr. Koestner's article in "Aspartame: Physiology and Biochemistry" published by Marcel Dekker, page 447.) The *original* record clearly shows 12 brain tumors in the test animals and zero in the controls as stated by Dr. Olney: "There were other problematic aspects of the brain tumor data. In the pre-1975 records that I reviewed, it was clear that several competent pathologists had carefully examined the original microscopic slides from the first study and agreed that there were 12 brain tumors in the NutraSweet- fed rats and zero brain tumors in the controls. When the FDA conducted a task force investigation of these laboratories in 1975, they singled out these studies for further investigation and ordered that all laboratory records, including microscopic slides etc. be impounded under FDA seal. Several years later when a group of pathologists (UAREP) was sent to authenticate these studies, they could not find the microscopic slides. The UAREP pathologists were finally taken to a laboratory where the slides were not supposed to be and there they found some but not all of the original slides. Clearly they had not been kept under FDA seal and by mysterious coincidence the slides that were finally presented to the UAREP pathologists contained evidence for 11 brain tumors in Nutrasweet-fed rats and 1 tumor in contols. It is important to recognize that if there are zero tumors in the controls, it is very difficult to argue that the tumor incidence in the control and Nutrasweet-fed rats is the same. But if there is 1 tumor in the control group, it is possible with statistical acrobatics to reach the conclusion that the incidence is the same. And, indeed, this is exactly the argument that the manufacturer and the FDA Bureau of Foods pressed at the Public Board of Inquiry. They accepted the finding of 1 brain tumor among the controls even though the authentic record showed zero brain tumors in the controls, then they proceeded to break down the animals into smaller and smaller sub groups according to sex, dose level etc. and finally the 1 brain tumor in one sub group of control animals appeared to be not significantly different from 2 or 3 tumors in each of the experimental sub groups. I seriously doubt whether this method of data analysis would stand the scrutiny of competent disinterested statisticians. Even more seriously I wonder why FDA allows microscopic slides to disappear (while supposedly impounded) and why they do not question the de novo emergence of a brain tumor among the controls when the slides reappear." > "Since aspartame in the two Searle-Hazelton studies did not fulfill > any of the criteria established for neurocarcinogenic agents and > since the incidence of brain tumors was well within the range of > spontaneous brain tumors in 2-year-old Sprague Dawley rats, there can > be no causal link between aspartame and brain tumors observed in the > Searle-Hazelton studies." Dr. Koestner is arbitrarily stating that aspartame does not meet the criteria established for neurocarcinogenic agents. He goes into detail in the chapter from the book mentioned above. His arguments in that chapter are badly flawed as I discuss in detail in the draft scientific/history review of aspartame ("Aspartylphenylalanine Diketopiperazine (DKP)" chapter) on my web page: < http://www.holisticmed.com/aspartame/ > Twelve brain tumors in the aspartame-fed rats was well outside the spontaneous brain tumor rates for 2-year-old Sprague Dawley rats. He is just making up statements out of the blue now. The Public Board of Inquiry which included the President of the American Association of Neuropathologists (and which unanimously voted *against* aspartame approval because of the brain tumors) found that the spontaneous brain tumor rate would be somewhere around 0.7% -- many times below the brain tumor rate of 3.75% found in one pre-approval study and over 3% in another pre-approval study. The FDA Commissioners own scientists were against approval and worried because of this brain tumor rate. The FDA Commissioner used a study that *did not* discuss methodoloy at all to guess that the spontaneous brain tumor rate was 2.2% (still below what was found in the pre-approval experiments). But he apparently felt it was close enough and decided to approve aspartame. And as is well-known, he became a high-paid consultant for the manufacturer's PR firm shortly thereafter. Dr. Gary Flamm --------------- > "The paper misstates critical facts and totally ignores important > facts such as the third carcinogenicity study conducted on aspartame > in rats which confirmed earlier findings that aspartame is not > carcinogenic." As is discussed in the draft review on my web page, Dr. Olney points out that 1) this study was not used in the determination for aspartame approval (as admitted to by the FDA Commissioner), 2) it appeared in a poor quality journal, 3) the report was sketchy (i.e., not detailed), and 4) the type of rats used was different than in the pre-approval studies. I further point out that the study was conducted by a close business partner of the manufactuer, Ajinomoto (who is now producing aspartame). Ajinomoto was a major part of the International Glutamate Technical Committee (IGTC). During that period of time, the IGTC funding "research" that including hiding aspartame in the drink mix of MSG experiments, using a brain protective substance on animals before giving the animals the test substances (including aspartame and MSG), and recropping a picture from an old experiment to show "no damage" in a newer experiment. One has to be unbelievably gullible to accept any sketchy study from Ajinomoto during this period of time. > "I also deeply resent the insinuation that the FDA Commissioner > approved aspartame on the basis of his judgment alone with no support > from experts in carcinogenesis. This charge is clearly contradicted > by the written record...." As Dr. Olney points out: "Also highly relevant is the fact that in the 1980 FDA convened a Public Board of Inquiry (PBOI) where a panel of scientists, including prominent neuroscientists (Walle J.H. Nauta and Peter W. Lampert), were asked to evaluate evidence from two animal studies potentially linking aspartame to malignant astrocytic brain tumors. The PBOI panel concluded that evidence from one study was 'bizarre' and totally unreliable, and evidence from the other study appeared to show that 'aspartame may contribute to the development of brain tumors.' .... The FDA Commissioner who received the PBOI report referred it to additional expert FDA consultants who concurred with the PBOI panel's recommendations." Please note that Dr. Peter W. Lampert was, at that time, the President of the American Association of Neuropathologists and, by far, the most qualified member of the PBOI to judge whether aspartame had the potential to cause brain tumors. He never waivered from his position that more studies were needed before approval should be allowed. From the FDA Commissioner's statement approving aspartame in 1981 (Federal Register, Vol. 46, No 142., 7/24/81) one can see that he relied only on his own judgement (or lack thereof) and a review performed by the FDA Bureau of Foods. It is surprising to say the least that the FDA Commissioner would ignore the PBOI suggestions, the suggestion of the FDA Commissioner's review team and instead accept a report from the FDA Bureau of Foods. > "While nitrosation of aspartame or DKP is theoretically possible as > discussed in the paper cited by Shephard et al., the product would > not be nitrosourea as was incorrectly stated by the authors. The > formation of nitrosamides would, if it occurred, proceed through > nitrosation of the peptide bond. The quantity of nitrosated product > produced with aspartame would be minuscule compared to that which > would form with dietary protein and peptides. Reaction of peptide > bonds proceed very slowly and are not considered to be a public > health problem." As Olney pointed out, the Shephard paper showed that "if aspartame is nitrosated in vitro to simulate the nitrosation that is believed to occur in the stomach, the nitrosated product has substantial mutagenic activity." That is what Shephard et al. found. If Dr. Flamm believes that the conversion of DKP to other chemicals does not create a mutagenic compound, then he should push for completely independent research to address this issue (as should have been done many years ago before approval was granted). Dr. Olney points to this as a possibility as to how aspartame may contribute to brain cancer. As I point out in my draft review, one cannot discount the effects of other breakdown products of aspartame contributing to the increase in the deadlier forms of brain cancer without adequate research. > "In conclusion, I am in deep despair over the damage the subject > paper may do to the credibility of science and to the FDA. The paper > has replaced proper scientific analysis of all relevant data with a > selective picking of just that which might support their groundless > speculation." The manufacturer of aspartame, Monsanto/NutraSweet has long since begun the destruction of the scientific process by conducting experiments on aspartame that can generously be described as "deceptive." The fact that several officials at the FDA obtained key positions in the aspartame industry and that since that time the FDA has done everything possible (including banning safe sweeteners) to help the manufacturer push aspartame on the public only serves to dig a deeper hole for the FDA. If the FDA reputation is irrepairbly damaged, the FDA officials need only look in the mirror to discover the cause of the problem. Then they should look at the large and growing number of serious toxicity reactions caused by aspartame. (See samples on my web page.) In conclusion, Dr. Olney is correct in his call for independent studies to look at the aspartame and brain cancer issue. He points out that aspartame meets the three main criteria usually invoked in evaluating the potential of an environmental agent to behave as a human carcinogen. a. Aspartame has been shown to have in vitro mutagenic potential. b. There was an increased in incidence of specific types of cancer when animals were exposed to aspartame. c. Humans have shown an increase (especially susceptible populations) in the same types of cancer since not long after aspartame has been approved. Dr. Olney is not asserting that he proved that aspartame causes brain cancer. However, he is calling for indenpendent research to settle the matter before it is too late. Obviously, there are many reasons why one would not choose to slowly poison onself with chronic, long-term aspartame use, even if aspartame didn't cause brain cancer. See the web page address below for more information. - Mark Gold mgold@holisticmed.com http://www.holisticmed.com/ http://www.holisticmed.com/aspartame/