Aspartame

[Pan]

Just speaking for myself, I would observe that Sam does not disagree in order to be disagreeable. If you don't like arguments that are on-topic, a discussion board is definitely not for you. But the pity is, if you don't make any further replies, you can't give us specific references to the studies you generically refer to. Could or would you please advance the discussion on aspartame by pointing to some studies that show any kind of danger from the substance? Frankly, I am suspicious of aspartame (and hate its taste, anyway), but when I did a PubMed search, I found that all referenced studies in recent years showed nothing but positive effects from aspartame. So if you'd just thicken your skin a little bit, we might yet derive some benefit from your presence in this thread.

[alacarte]

If you just want to focus on the taste of Splenda vs. Nutrasweet vs. plain old sugar, I recommend this article, which ran on Slate awhile back.

[mudbug]

I've grown stevia. Stevia is an herb and it is a wonderful alternative for sugar and sugar substitutes. Just top by a farmer's market in the spring or a greenhouse. Pick of a leaf of the plant and chew it. You'd be amazed how sweet it is.

Last month I posted a question regarding making sugarless peanut brittle from scratch and Whey Low was recommended. I ordered it and made the brittle. It came out very well. No complaints.

Whey Low

[Pan]

My father has a fair degree of glucose intolerance (I think it's called), so he generally substitutes stevia where sugar is called for in recipes. He finds that he gets the same degree of sweetness as expected when he uses half the amount of stevia that he would have used of sugar. (I had trouble figuring out how to write that sentence clearly; did that work? )

Mudbug, where are you located? I understand that most stevia is grown in Argentina, I think Patagonia?? Which would call for a cool, pretty dry climate, I imagine.

[jsolomon]

jsolomons - yeah i know - i don't put a whole lot of stock in the FDA anyway - too deep in the pockets of the Pharmaceuticals.

I think you're taking me out of context. I put a lot of faith in the FDA. I work in the medical field giving drugs to poor saps who come under my care, and I have spent time researching drugs as well. I think there are a good many times that the FDA has come through for Americans. Granted, I can think of at least as many ways in which their oversight has kept beneficial drugs from coming to the pharmacopeia. But, a lot of my criticism of the FDA is a social argument and a satiric commentary on our current society.

Be that as it may, allergic reactions can be very serious life threats at times. I applaud you for listening to your body. However, since I don't hold that foodstuffs such as peanuts which have a higher incidence of serious allergy should have a warning lable or be pulled from the shelves, I don't think that aspartame should be pulled because of a handful of isolated allergies. At some point the consumer has to take responsibility for the foods they put in their mouths, just as the consumer, not the producer is responsible when some poor shlub chokes to death in a steak house because he couldn't chew his well-done piece of leather.

That's why I get mine seared and warm, and not much else

[tryska]

i don't feel it should be banned - just as i don't feel anything should be banned - what we put inside ourselves should be at our discretion, and i guess that's where my libertarian streak comes through. But i do believe that people should have all the facts, and listen to their bodies - if it's not good to you, it's probably not good for you - and that applies to just about everything. *lol*

[jat]

Even though I have decided not to engage in forum discussions , except the

RecipeGullet and it's discussion board, I feel that Aspartame IS an important

issue that deserves proper consideration. I would like to make a comparison to

it's use to cigarettes, being that people should be informed and be able to decide

for themselves what to do with that information. So I hope some of the information

will shed a little light and help others to question the possible risks to their health.

I feel all aspects need to be discussed. Everything from it's history, current

independent research studies, case histories, etc, Due to the verbage of replys

here, I better provide some excellent supporting information and I feel I do have

some to share. It is extensive and needs to be to cover this properly.

I contacted the writer of the medical journal I quoted from and also I contacted

Mark Gold, who is familiar with the world research on aspartame toxicity and

who speaks regularly with independent scientists around the world on the issue.

He is currently arranging a collaboration between independent scientists in the U.S.

and Europe to further study aspartame toxicity issue.

He told me that it was important that persons differentiate between studies

conducted by the manufacturer and their consultants and independent studies.

Manufaacturer funded studies appear convincing in summary form, but when

lookin at the complete publication one sees numerous deceptive practices that

we will discuss later. After I present ALL the information, Mark is willing

to discuss more.

As an INTRODUCTORY comment, the evidence related to toxicity of aspartame

is found primarily is three areas:

1. Formaldehyde Exposure. The formaldehyde exposure from aspartame is

significant. Aspartame breaks down into methanol, amino acids and several

other chemicals. The methanol is quickly absobed and converted into formaldehyde. THe methanol found in foods and alcoholic beverages is also

absorbed, but there are protective chemical in these traditionally ingested foods and beverages that prevents the conversion of methanol to formaldehyde.

Formaldehyde is known to cause gradual damage to the nervous sysstem, the immune system and has recently been shown to cause irreversible genetic damage

at long-term, low-level expossure.

The most recent, independent research shows that the situation related to aspartame may be more serious than simply regular formaldehyde exposure. The research on animals demonstrates that the formaldehyde appears to accumulate

as adducts (bound to protein molelcules) in the organs and tissues of the animals (when aspartmae is ingested at relatively low doses):

"These are indeed extremely high levels for adducts of formaldehyde, a substance responsible for chronic deleterious effects that has also been considered carcinogenic. It is concluded that a consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts." -Life Sciences,

(Scientific Journal), Vol. 63, No. 5, pp, 337 l998.

A comment from an independent research scientist regarding this and other

recent aspartame research:

"It was a very interesting paper that demonstrates that formaldehyde formation from aspartame ingestion is very common and does indeed accumulate within the cell, reacting with cellular proteins (mostly enzymes) and DNA )both

mitochondrial and nuclear). The fact that it accumulates with each dose, indicates

grave consequences among those who consume diet drinks and food stuffs on a

daily basis." - Russell Blaylock, MD Neurosurgeon and Neuroscientist.

The damage caused by formaldehyde from aspartame may be worsened by

other aspartame breakdown chemicals, especially the aspartic acid. In animal reasearch where formaldehyde is given to the animals to cause damage and pain, amino acids such as aspartic acid and glutamic acid are given at the same time

to worsen reaction. The amino acids from aspartame are absorbed suddenly

unlike protein-bound amino acids found in food.

2. Independent reasearch finds problems with aspartame. An analysis of peer reviewed medical literature using MEDLINE and other databases was conducted by

Ralph G. Walton, MD Chairman. The Center for Behavioral Medicine, Professor of Clinical Psychiatry, Northeastern Ohio Universities College of Medicine. Dr. Walton analyzed 164 studies which were felt to have relevance to human safety questions. Of the 90 non industry-sponsored (independent) studies, 83 (92%)

identified one or more problems with aspartame. Of the 74 aspartame industry sponsored studies, all 74 (100%) claimed that no problems were found with aspartame.

3. Extremely large number of reported toxicity reactions to aspartame. As of

1995 when the U.S. Food and Drug Administration (FDA) was quoted as saying they stopped accepting adverse reaction reports on aspartame, over 75 %

of the adverse reactions reported to the FDA Adverse Monitoring Systems,

(ARMS) were due to aspartmae. After considering the fact that an extremely low

percentage of adverse reactions are reported to the FDA< it becomes clear that there are milliions of known cases of aspartame toxicity reactions and possibly many other cases where the person ingesting aspartame is either 1) unaware that

their symptoms are caused or contributed by aspartame; or 2) not yet experiences clinically obvious symptoms from the breakdown products of aspartmae, but may eventually experience chronic health problems fromt he regular exposure to significant doses of formaldehyde. Some of the toxicity symptoms reported include seizures, headaches, memory loss, tremors, convulsions, vision loss, nausea, dizziness, confusion, depression, irritability,

anxiety attacks, personality changes, heart palpitations, chest pains, skin diseases, loss of blood sugar control, arthritic symptoms, weight gain, excessive thirst or

urination. Regular exposure to a toxic substance such as formaldehyde may

worsen, or in some cases contribute to the development of chronic diseases.

Before I get upset responses, please let me PROVIDE ALL THE INFORMATION,

research data, etc. I will start this discussion on the beginning and history and

background material of aspartame. Right now I need to do breakfast.

[jsolomon]

It sounds to me like the clear solution to the problem is to make sure and ingest ethanol whenever you are ingesting aspartame to make sure that you counteract any sort of methanol/formaldehyde toxicity.

Hmm... sounds like a good reason to drink Irish coffee

[slkinsey]

1. From a letter in The Lancet:

Aspartame, a dipeptide composed of phenylalanine and aspartic acid linked by a methyl ester bond, is not absorbed, and is completely hydrolysed in the intestine to yield the two constituent aminoacids and free methanol. Opponents of aspartame suggest that the phenylalanine and methanol so released are dangerous. In particular, they assert that methanol can be converted to formaldehyde and then to formic acid, and thus cause metabolic acidosis and neurotoxicity.

Although a 330 mL can of aspartame-sweetened soft drink will yield about 20 mg methanol, an equivalent volume of fruit juice produces 40 mg methanol, and an alcoholic beverage about 60-100 mg. The yield of phenylalanine is about 100 mg for a can of diet soft drink, compared with 300 mg for an egg, 500 mg for a glass of milk, and 900 mg for a large hamburger. Thus, the amount of phenylalanine or methanol ingested from consumption of aspartame is trivial, compared with other dietary sources. Clinical studies have shown no evidence of toxic effects and no increase in plasma concentrations of methanol, formic acid, or phenylalanine with daily consumption of 50 mg/kg aspartame (equivalent to 17 cans of diet soft drink daily for a 70 kg adult).

2. I note that Ralph G. Walton's study (aolready of dubious reliability, due to being a meta-analysis) is not published in a peer-reviewed journal.

3. The reason the FDA stopped tracking adverse reaction reports on aspartame is because they determined that they did not have any merit.

More information on the various anti-aspartame scams may be found here. As the good folks at about.com suggest, if the word of the FDA and the mainstream medical research community is not good enough for you, read through the last 20 years of research on Medline and decide for yourself.

[jat]

I will prove otherwise. Walton's import was simply in pointing out that

the independent studies showed that there is a problem with aspartame,

whereas the manufacturer, paying enourmous sums, does not report any

problems with aspartame.

I have spoken with many people, including my husband who report eliminating

their symptoms after quitting aspartame. BUt I'll report on this way later.

You will see why the history and background is so important, I'll post that next.

Edited January 19, 2004 by jat (log)

[jat]

How did the American Medical Association's Council on Scientific Affairs fail to

reveal toxic side effects on aspartame?

Let's look at the History:

1964 The development of new pharmaceuticals was the focus of research at the

international pharmaceutical company, G.D. Searle and Company (Farber 1989,

page 29). A group working on an ulcer drug was formed including Dr. Robert Mazer, James Schlatter, Arthur GOldkemp and Imperial Chemical. In particular, they were looking for an inhibitor of the gastrointestinal secretory hormone gastrin (Stegink 1984a, page 3).

l965 In 1965, while creating a bioassay, an intermediate chemical was synthesized- aspartyphenylalanine-methyl-ester (aspartme). In December of 1965, while James Schlatter was recrystalling aspartame from ethanol, the mixture spilled onto the outside of the flask. Some of the powder got onto his fingers. Later, when he licked his fingers to pickup a piece of paper, he noticed a very strong sweet taste. He realized that the sweet taste might have been aspartame. So, believing that the dipeptide aspartame wasnot likely to be toxic, he tasted a little bit and discovered its sweet taste (Stegink 1984a, page 4). The discovery was reported in 1966, but there was no mention of the sweetness (Furia, 1972).

1969 The investigators first reported the discovery of the artificial sweetener in the

Journal of the American Chemical Society stating (Mazur 1969):

"We wish to report another accidental discovery of an organic compaound with a profound sucrose (table sugar) like taste... Preliminary tasting showed this compound to have a potency of 100-200 times sucrose depending on concentration and on what other flavors are present to be devoid of unpleasant aftertaste."

In 1969, former Commissioner of the FDA, Dr. Herbert L. Ley was quoted as follows (Griffin l974):

"The thing that bugs me is that people think the Food and Drug Administration (FDA) is protecting them--it isn't. What the FDA is doing and what the public thinks it's doing and what the public thinks it's doing are as different as night and day."

1970 The discovery of aspartame is reported in the well-known publication, Science (Cloninger l970).

G.D. Searle approached Dr. Harry Waisman, Biochemist, Professor of Pediatrics, Director of the University of Wisconsin's Joseph P. Kennedy Jr. Memorial Laboratory of Mental Retardation Research and a respected expert in phenylalanine toxicity, to conduct a study of the effects of aspartame on primates. THe study was initiated on January 15, 1970 and was terminated on or about April 25, l971. Dr. Waisman died unexpectedly in March, l971.

Seven infant monkeys were given aspartame with milk. One died after 300 days. Five others (out of seven total) had grand mal seizures. The actual results were hidden from the FDA when G.D. Searle submitted its initial applications (Stoddard 1995a, page 6; Merrill 1977: graves 1984, page S5506 of Congressional Record 1985a: Gross 1976b, page 333 of US Senate 1976b).

G.D. Searle denied knowledge of or involvement with the initiation, design or performance of the study. Yet, the false results were submitted to the FDA like the rest of the 150 G.D. Searle studies (on aspartame and other products), bearing a Searle Pathology-Toxicology project number. Both Dr. Waisman and G.D. Searle were responsible for the study design. A number of false statements were unavailable for purchase for autopsy after the termination of the study.

Neuroscientist and researcher John W> Olney found that oral intake of glutamate, aspartate and cysteine (in free form-unbound to protein such as aspartate in aspartame), all excitotoxic amino acids, cause brain damage in mice (Olney 1970).

An internal G.D. Searle memo layed out the strategy for getting aspartame approved (Helling 1970):

At this meeting (with FDA officials). the basic philosophy of our approach to food and drugs should be to try to get them to say "Yes," to rank the things that we are going to ask for so we are putting first those questions we would like to get a "Yes" to, even if we have to throw some in that have no significance to us, other than putting them in a yes saying habit.

We must create affirmative atmosphere in our dealing with them. It would help if we can get them or get their people involved to do us any such favors. This would also help them into subconcious spirit of participation.

The FDA banned the sweetener cyclamate. Robert Scheuplein, who was acting Director of FDA's Toxocological Services Center for FOod Safety and Applied Nutrition was quoted as saying "the decision was more a matter of politics than science." (Stoddard 1995a, page 7).

1971 Ann Reynolds, a researcher who was hired by G.D. Searle and who has done research for the Glutamate (MSG) Association, confirmed aspartame's neurotoxicity in infant mice (Reynolds 1971).

Dr. John W. Olney informed G.D. Searle that aspartic acid caused holes in the brains of mice. G.D. Searle did not inform the FDA of this study until after aspartame's approval. None of the tests submitted by G.D> Searle to the FDA contradicted these findings (Olney 1970, Gordon 1987, page 493 of US Senate 1987).

1972 FDA Toxicologist Dr. Adrian Gross came upon some irregularities in the submitted tests of the G.D. Searle drug Flagyl. G.D> Searle did not respond for another two years. Their response raised serious questions about the validity of their tests (Gross 1975, page 35: Schmidt 1976b, page 6).

1973 On March 5, 1973, G.D. Searle's petition to the FDA for approval to market aspartame as a sweetening agent was ppublished in the Federal Register (1973).

On March 21, 1973, the MBR report was submitted to G.D. Searle.

Background: In August of 1970, G.D. Searle conducted two 78-week toxicity studies on rats for what was to become a best-selling heart medication, Alcactone. One study was conducted at G.D. Searle and one at Hazelton Laboratories. In March 1972, the rats for autopsied and the pathology slides were analyzed. For confirmation of the results, G.D. Searle sent the slides to Biological Research, Ltd.

where board certified pathologist, Dr. Jacqueline Mauro examined the data. She discovered that the drug appeared to induce tumors in the liver, testes, and thyroid of the rats. The report submitted to G.D. Searle by Dr. Mauro was known as the MBR Report.

These statistically significant findings were confirmed by G.D. Searle's Mathematics-Statistics Department. Instead of submitting these alarming findings to the FDA, G.D. Searle contracted with another pathologist, Dr. Donald A. Willigan. He was given 1,000 slides to examine. The Willigan Report was more to G.D. Searle's liking because it revealed a statistically significant increase in thyroid and testes tumors, but not in liver tumors. Liver tumors are of much more concern to the FDA. The Wilingan Report was immediately submitted to the FDA.

G.D. Searle did not disclose the MBR report until August 18, 1975, 27 months after it had been given to G.D. Searle (Schmidt 1976b, page 14, Merrill 1977, page S10828-S10831).

At first, G.D. Searle claimed that they did not submit the MBR Report to the FDA because of an "oversight". Later, they claimed that Dr. Mauro's MBR Report was not submitted because they did not like the terminology Dr. Mauro used in evaluating the thyroid slides. They claime that her inaccurate terminology in this case showed that Dr. Mauro was unreliable as a pathologist. Yet, G.D. Searle never notified Dr. Mauro of any questions and on June 1, 1973, they wrote to MBR and stated that the report "looks just fine" (Merrill l977).

( I will post this in case my computer erases it )

[jat]

The FDA Commissioner from 1972 to 1976, Alexander Schmidt, M.D. felt that "Superficially, it seemed like, if there would ever be a safe kind of product, that would be it. THe idea that two naturally occurring amino acids could harm someone in relatively small amounts.." (Mullarkey 1992, page 15)

In an FDA memorandum dated September 12, 1973, Martha M. Freeman, M.D. of the FDA Division of Metabolic and Endocrine Drug Products addressed the adequacy of the information by G.D. Searle in their petition to approve aspartame (Freeman 1973):

"Although it was stated that studies were also performed with diketoperazine (DKP) an impurity which results form acid hydrolysis of Aspartame, no data are provided on this product."

Commenting on one particular single dose study:

"It is not feasible to extrapolate results of such single dose testing to the likely condition of use of Aspartame as an artificial sweetener."

It is important to note that Dr. Freeman pointed out the inadequacy of single-sose tests of aspartame as early as 1973. Since then, the NutraSweet Company has flooded the scientific studies with single-dose studies.

"Chemistry - No information is provided other than formulas for Aspartame and its diketo-piperazine."

"Pharmacology - Reference is made to 2 year rat studies, but no data are provided on acute or chronic toxicity."

"Clinical - No protocols nor curriiculum vitae information are provided for the 10 completed clinical studies. Results are reported in narrative summary form, and tabulations of mean average values only. No information is given as to (except rarely), or normal values. (Reported units for several parameters cannot be verified at the time.)

"No pharmacokinetic data are provided on absorption, excretion, metabolism, half-life: nor bioavailability of capsule vs. food-additive administration."

Dr. Freeman concludes:

"1. The adminstration of Aspartame, as reported in these studies at high dosage levels for prolonged periods, constitutes clinical investigational use of a new drug substance."

"2. THe information submitted for our review is inadequate to permit a scientific evaluation of clinical safety."

She went on to recommend that marketing of aspartame be contingent upon proven clinical safety of aspartame. The FDA Bureau of Foods rejected Dr. Freeman's recommendation (Graves 1984, page S5498 of Congressional Record 1985a).

Construction of a large aspartame manufacturing plant in Augusta, Georgia was halted. It was thought that aspartame's uncertain regulatory future was the main reason for the stopping of construction (Farber 1989, page 47). In the 1973 G.D. Searle Annual Report, an executive stated that "commercial quantities of the sweetener will be supplied from the enlarged facility of Ajinomoto." Ajinomoto is the inventor and main producer of the food additive MSG>

1974 Ninety of the 113 aspartame studies which were submitted by G.D. Searle to the FDA were conducted in the early to mid-1970's. All of the tests that were described by the FDA as "pivotal" were conducted by G.D. Searle or by their major contractor, Hazelton Laboratories, Inc. (Graves 1984, page S5397 of Congressional Record 1985a).

Dr. J. Richard Crout, the acting director of the FDA Bureau of Drugs stated that "The information submitted for our review was limited to narrative clinical summaries and tabulated mean values of laboratory studies. No protocols, manufacturing controls information or preclinical data were provided. Such deficiencies in each area of required information precluded a scientific evaluation of the clinical safety of this product..." (Mullarkey 1992, page 23)/

Dr. John Olney and Consumer Interest attorney, James Turner, Esq. met with G.D. Searle to discuss the results of Olney's experiments. G.D. Searle represenatives claim that Olney's data raises no health conerns (Stoddard 1005a, page 7).

The FDA approved aspartame for limited use on July 26, 1974. The allowable uses included free-flowing sugar substitiute, tablets for sweetening hot beverages, cereals, gum, and dry bases (Farber 1989, Federal Register 1974). It was not approved for baking goods, cooking, or carbonated beverages. This approval came despite the fact that FDA scientists found serious deficiencies in all of the 13 tests related to genetic damage which were submitted by G.D. Searle.

In August 1974, befor Aspartame could go on the market, Dr. John Olney, James Turner, and Label Inc, (Legal Action for Buyers' Education and Labeling) filed a formal objection stating that they believe aspartame could cause brain damage. THey were particularly worried about aspartame's effects on children (graves 1984, page S5498 of Congressional Record 1985a: Federal Register l075, Olnay 1087, page 3).

G.D. Searle's response to queries about the testing of their drug Flagyl, serious and unexpected side effects from other drugs they developed, and information from Dr. John Olney's studies started a controversy within the FDA as to the quality and validity of G.D. Searle's test of aspartame and pharmaceuticals (Graves 1984 page S5498 of Congressional Record 1985a).

1975 In July 1075, the FDA COmmissioner, Dr. Alexander Schmidt appointed a special Task Force to look at 25 key studies for the drugs Flagyl, Aldactone, Norpace, and the food additive aspartame. Eleven of the pivotal studies examined involved aspartame. All of the studies whether conducted at G.D. Searle or Hazelton laboratories were the responsibility of the Pathology)Toxicology Department of G.D. Searle. (Gross 1987a, page 430 of the US Senate 1980). The special Task Force was headed by Philip Brodsky, FDA's lead investigator and assisted by FDA Toxicologist, Dr. Adrian Gross. The Task Force was especially interested in "pivotal" tests ad described in an article from Commoon Cause Magazine by Florence Graves (Graves 1984, page S5499 of Congressional Record 1985a):

"Before the task force had completed its investigation in 1976, Searle had submitted the vast majority of the more than 100 tests it ultimately gave the FDA in an effort to get aspartame approved. These included all tests ever described as "pivotal" by the FDA> About half the pivotal tests were done by Searle; about

one-third were done at Hazelton Laboratories. 'Pivotal' tests include lont-term (two-year-tests such as those done to determine whether aspartame might cause cancer. Former FDA commissioner Alexander Schmidt said in a recent inerview that if a pivotal test is found to be unreliable, it must be repeated 'Some studies are more important than others, and they have to be done impeccably.' Schmidt said."

G.D. Searle executives admitted to "payments to employees of certain foreign governments to obtain sales of their products." (Searle 1975).

[jat]

On July 10, 1975, Senator Edward Kennedy chaired a hearing on drug-related research before the Senate Subcommittee on Health of the Committee on Labor and Public Welfare (US Senate 1975). Preliminary reports of discrepancies discovered about G.D. Searle were discussed. The findings of the FDA Task Force were later presented at further hearings on January 20, l976 (US Senate 1976a) and April 8, 1976 (US Senate 1976b).

On December 5, l975, Dr. John Olney and James Turner waived their right to a hearing at the suggestion of the FDA General Counsil after the FDA and G.D. Searle agreed to hold a public Board of Inquiry (PBOI) (Federal Register 1975, page 286, Mullarkey 1994b, page 5-6).

On December 5, l975, the FDA put a hold on the approval of aspartame due to the preliminary findings of the FDA Task Force. The Public Board of Inquiry is also put on hold (Mullarkey 1994b, page 5-6: Federal Register 1975). The evidence of the

aspartame pivotal studies were protected under FDA seal on December 3. 1975 (Sharp l975).

G.D. Searle had invested 19.7 million dollars in an incomplete production facility and 9.2 million dollars in aspartame inventory. On December 8, l975, stockholders filed a class action lawsuit alledging that G.D. Searle had concealed

information from the public regarding the nature and quality of animal research

at G.D. Searle in violation of the Securities and Exchange Act (Farber 1989, page 48).

1976 On January 7, l976, G.D. Searle submitted to the FDA their proposal for the adoption of "Good Laboratory Practices" (Buzzard 1976b). G.D. Searle's input was used in FDA's adoption of Good Laboratories Practice.

In March 1976, the FDA Task Force completed a 500-page report with 15,000 pages of exhibits (80 page summary) to the FDA after completing their investigation (Schmidt 1976c, page 4 of US Senate 1976b).

"Practices that were noted in connection with any given such study were quite likely to have been noted also for other studies that were audited, and this was a situation which was in no way unexpected; after all, the set of all such studies executed by that firm from about 1968 to the mid-seventies were conducted in essentially the same facilities, by virtually the same technicians, professional workers and supervisors, and the nature of such studies does not differ much whether a food additive or a drug product is being tested for safety in laboratory animals. It is in this sense, therefore, that the overall conclusion summarized at the beginning of the Searle Task Force Report have relevance to all the studies audite in 1975 (whether they had references to aspartame or to any of the six drug products of experimental studies carried out by that firm around that time- 1968-1975."

A few of the conclusions of the FDA Task FOrce (Gross 1987a,page 2-3):

"At the heart of the FDA's regulatory process is its ability to rely upon the integrity of the basic safety data submitted by sponsors of regulated products. Our investigation clearly demonstrates that, in the case of G.D. Searle Company, we have no basis for such reliance now."

"We have noted that Searle has not submitted all the facts of experiments to FDA,

retaining unto itself the unpermitted option of filtering, interpreting, and not submitting information which we would consider material to the safety evaluation of the product.. Finally, we have found instances of irrelevant or unproductive animal research where experiments have been poorly conceived, carelessly executed, or inaccurately analyzed or reported."

"Some of our findings suggest an attitude of disregard for FDA's mission of protection of the public halth by selectively reporting the results of studies in a manner which allay the concerns of questions of an FDA reviewer."

"Unreliability in Searle's animal research does not imply, however that its animal studies have provided no useful information on the safety of its products. Poorly controlled experiments containing random errors blur the differences between treated and control animals and increase the difficulty of discriminating between the two populations to detect a product induced effect. A positive finding of toxicity in the test animals in a poorly controlled study provides a reasonable lower bound on the tru toxicity of the substance. The agency must be free to conclude that the results from such a study, while admittedly imprecise as to incidence or severity of the untoward effect, cannot be overlooked in arriving at a decision concerning the toxic potential of the product." ( )

A few of the relevant findings summarized from various documents describing the FDA Task Force Report:

a. "Excising masses (tumors) from live animals, in some cases without histologic

examination of the masses, in others without reporting them to the FDA."( )

(Schmidt 1976c,page 4 of US Senate l976b) Searle's representatives, when caught andquestioned about these actions, stated that "these masses were in the head and neck area and prevented the animals from feeding." (Buzzard 1976a)

"Failure to report to the FDA all internal tumors present in the experimental rats, e.q./polyps in the uterus, ovary neoplasms as well as other lesions." (Gross 1987a,page 8).

b. G.D. Searle "stored animal tissues in formaldehyde for so long that they deteriorated." (Gordon 1987, page 496 of US Senate l987: US Schmidt 1976c, page 25, 27 of US Senate 1976b).

c. "Instead of performing autopsies on rhesus monkeys that suffered seizures after being fed aspartame, the company had financed a new monkey seizure study with a different methodology that showed no problems." (Gordon 1987, page 496 of US Senate l987)

d. "Reporting animals as unavailable for necropsy when, in fact, records indicate that the animals were available but Searle chose not to purchase them." (Schmidt 1976c, page 5 of US Senate 1976b).

e. "Animals which had died were sometimes recorded as being alive and vice versa. "These include approximately 20 instances of animals reported as dead and then reported as having vital signs normal again at subsequent observation periods." ( ) (Gross 1985, page S10835)

f. "Selecting statistical procedures which used a total number of animals as the denominator when only a portion of the animals were examined, thus reducing the significance of adverse effects." (Schmidt 1976c,page 4 of US Senate 1976b)

g. G.D. Searle told the FDA that 12 lots of DKP were manufactured and tested in one study, yet only 7 batches were actually made. (Gross l985, page S10835)

h. "Significant deviations from the protocols of several studies were noted which may have compromised the valuse of these studies.. In at least one study, the Aspartame 52 weeks monkey study, the protocol was written after the study had been initiated." (Gross 1985, page S10835)

i. "It is significant to note that the Searle employee responsible for reviewing most of the reproduction studies had only one year of prior experience, working on population dynamics of cotton tail rabbits while employed by Illinois Wildlife Service. In order to prepare him for this title of 'Senior Research Assistant in Teratology' (fetal damage) Searle bought him books to read on the subject and also sent him to a meeting of the Teratology Society. This qualified him to submit 18 of the initial tests to the FDA, in addition to training an assistant and 2 technicians. He kept them busy because Searle claimed that 329 teratology examinations were conducted in just 2 days. He estimated that he himself examined about 30 fetuses a day, but officials for the Center for Food and Applied Nutritiion could never determine how that was possible." (Stoddard 1995, page 9: Graves 1984, page S5500 of Congressional Record 1985a)

j. "In each study investigated, poor practices, inaccuracies, and discrepancies were noted in the antemortem phases which could compromise the study." (Gross 1985, page S10836 of Congressional Record 1985b)

k. "Presenting information to FDA in a manner likely to obscure problems, such as editing the report of a consulting pathologist.. Reporting one pathology report while failing to submit, or make reference to another usually more adverse pathology report on the same slide." ( ) (Schmidt 19766c,page 4-5 of US Senate 1976b)

l. Animals were not removed from the room during the twice per month exterminator sprayings. (Gross 1985, page S10836 of Congressional Record 1985b)

m. Often the substance being tested which was given to animals was not analyzed or tested for homogeneity. "NO records were found to indicate that any treatment mixtures used in the studies were ever tested or assayed for pesticide content..Running inventory records for either treatment mixtures or the test compounds used in treatment mixtures are not maintained." (Gross 1985, page S10836 of Congressional Record 1985b)

n. In the Aspartame (DKP) 115 wek rat study the writte observatins of the pathology report was changed by the supervising pathologist, Dr. Rudolph Stejskal even though he was not physically presnet during the autopsies and could not have verified the observations of the pathologist who did perform the autopsies. The pathologist who did perform some of the autopsies had no formal training for such procedures. (Gross 1985, page S10837 of Congressional Record 1985b)

o. "Contrary to protocol, slides were not prepared of this unusual lesions from the Aspartame (DKP) study tissue for microscopic examinations." (Gross l985, page

S10837 of Congressional Record l985b)

( I will try to continue tomorrow, I am just trying to establish the importance of

reliability in comparing Independent Research, when I show the current findings.)

[slkinsey]

Um... so what? There still remains the fact that the vast majority of reputable, peer-reviewed science does not support the assertion that aspartame is any more unsafe than, say, mangos.

[cdh]

apparently i'm part of that minority that gets headaches, chills, and fatigues from nutrasweet (nothing makes me crash out faster than being accidentally dosed with diet coke), gets damn near anaphylactic shock  from ace-k (tingly back of the tongue, it swells, i find it hard to breathe etc)...

That's very odd. The FDA says that "carefully controlled clinical studies show that aspartame is not an allergen."

I wonder if it's something else. Do you get the same reaction from just raw aspartame by itself? I wonder if if would happen if you drank a diet coke that had been spiked with enough high fructose corn syrup that you were unable to taste the difference. I am not suggesting, of course, that you don't react the way you say you react. I just wonder a bit about what might be causing it.

Upon reading through this thread, the thought of checking out what Harold McGee had to say about aspartame in 1984 came to mind. He's somewhat enlightening, I think:

It has the disadvantages of breaking down and losing its sweetness at cooking temperatures and in acid foods, and of being unsafe for people who are born with the metabolic defect called phenylketonuria and who must limit their intake of phenylalanine.

Maybe those who react adversely are sufferers of this metabolic problem, rather than victims of some great conspiracy to market poison to the masses? Regardless of what the FDA says or does, companies pushing Aspartame could get bankrupted by a well placed lawsuit if proof of the poison conspiracy to a jury were possible. Since that hasn't happened... well... I'll continue my practice of avoiding diet stuff anyway.

Edited January 19, 2004 by cdh (log)

[slkinsey]

Upon reading through this thread, the thought of checking out what Harold McGee had to say about aspartame in 1984 came to mind.  He's somewhat enlightening, I think:

It has the disadvantages of breaking down and losing its sweetness at cooking temperatures and in acid foods, and of being unsafe for people who are born with the metabolic defect called phenylketonuria and who must limit their intake of phenylalanine.

Maybe those who react adversely are sufferers of this metabolic problem, rather than victims of some great conspiracy to market poison to the masses?

This specifically refers to people with phenylketonuria (PKU). PKU is a rare inherited disease in which individuals cannot properly metabolize the amino acid phenylalanine. This is why all products containing aspartame in the US feature the warning: "Phenylketonurics: Contains Phenylalanine."

I don't think its possible to have a "mild case of PKU" or to be a phenylketonuric and not know about it. It is a very serious disease.

[jat]

Continuing the history later, much will be disclosed.

In response to some posts with the help of M. Gold information, lets clarify a

few things.

I note that Ralph G. Walton's study (already of dubious reliablility, due to being

a meta-analysis) is not published in a peer-reviewed journal.

It does not matter that Dr. Walton's study was not published in a journal. Anyone

who has read the scientific research on aspartame knows that independent

studies have found that aspartame causes health problems and that manufacturer-sponsored studies claim that it is safe. For example, the recent study showing a significant formaldehyde accumulation in the body from aspartame ingest was an independent study. The recent study linking aspartame to fibromalgia symptoms was an independent study. Two studies demonstrating migraines/headaches from aspartame use were independent studies. Two studies showing adverse effects on the memory from aspartame use were independent studies.

The reason why manufactuere-sponsored studies show no problems is simply because they were designed in a way to avoid finding problems. For example, two

manufacturer-sponsored studies on aspartame and seizures-- the subjects were taking anti-seizure medication during the study! Such deception is only obvious upon reading the complete published study. Medline abstracts are meaningless

because they leave out enormous amounts of key information. No serious scientist

would rely on Medline abstract for information for the following reasons:

1) Medline is only one of several important databases, and

2) the abstracts usually do not disclose funding sources, use of active placebos,

improper statistical methods, giving brain-protective drugs to subjects taking aspartame during the study, etc.

The reason the FDA stopped tracking adverse reaction reports on aspartame is they determined they did not have any merit.

When one talks about the FDA (or any government agency for that matter), it is

important to distinguish between the bureaucrats who have no understanding of the science and the actual government scientist.

There are articles on the internet written by FDA Scientists or former scientists who are actually familiar with the research. One article can be found at:

http://health.groups.yahoo.com/group/aspartame/message/13306

More information on the various anti-aspartame scams may be found here.

Persons running urban legend sites are good for things like spiders under the

toilet seat and such. But when it comes to science, they have no knowledge of the scientific literature (except perhaps reading a few summaries). It is important

to get information directly from scientists who: 1) have proven knowledge of the

scientific leterature (not just summaries), and 2) have no financial connection to the manufacturer or their trade groups. That is a useful practice when looking into any scientific issue.

Um.. so what? There still remains the fact that the vast majority of reputable, peer-reviewed science does not support the assertion that aspartame is any more unsafe than, say, mangoes.

Toxicity or adverse health effects of compounds are not determined by counting the number of studies. One actually has to read the full published studies. The latest research has already demonstrated the following:

1. A significant formaldehyde exposure and accumulation from aspartame ingestion.

"These are indeed extremely high levels for adducts of formaldehyde, a substance responsible for chronic deleterious effects that has also been considered carcinogenic.

"It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts." Life Sciences, Vol. 63

No.5, pp 337+, l998.

Recent research demonstrated this, but the funny/sad thing is that one can see it not being eliminated from the body in the pre-approval research, but it was overlooked by the FDA. The best one can hope for from the chronic formaldehyde exposure is the irreversible genetic damage seen in long-term human studies usually, it causes or contributes to neurological or immunological problems over

time - eerily similar to symptoms from long-term aspartame use.

2. A large number of independent studies finding problems with aspartame. This includes double-blind, human studies, animal studies, clinical studies, etc. Some of the more recent independent studies involved aspartame and fibromyalgia, adverse memory effects and brain tumors. But there are older independent studies demonstrating adverse effects as well.

I will continue with the important History, and eventually you will see the reasons

why this is so significant.

[jat]

History Continued:

o. "Contrary to protocol, slides were not prepared of this (unusual) lesions from the Aspartame (DP) study tissue for microscopic examinations.." (Gross 1985, page S10837 of Congressional Record 1985b)

p. "In the Aspartame 46 weeks hamster study, blood samples reported in the submission to FDA as 26 week values (For certain specified animals) were found by our investigators as being, in fact, values for different animals which were bled at the 38th week. Many of the animals for which these values were reported (to the FDA) were dead at the 38th week." (Gross 1985, page S10838 of Congressional Record l985b)

"It is apparent from the report, that the Appendix portion contains all the individual (animal) values of clinical lab data available from the raw data file. A selected portion of these values appears to have been used for selecting a portion of the data or for deleting the others in computing the means (reported to the FDA)."

(Gross l985, page S10838 of Congressional Record l985b)

q. "Searle technical personnel failed to adhere to protocols, make accurate observations, sign and date records, and accurately administer the product under test and proper lab procedures." (Farber 1989, page 109)

r. (There were) "clerical or arithmetic errors which resulted in reports of fewer

tumors." (Schmidt 1976c, page 27 of US Senate l976b)

s. (G.D. Searle) "delayed the reporting of alarming findings." (Schmidt 1976c, page 27 of US Senate 1976b)

FDA Toxicologist and Task Force member, Dr. Andrian Gross stated (Wilson 1985):

"They (G.D. Searle) lied and they didn't submit the real nature of their observations because had they done that it is more than likely that a great number of these studies would have been rejected simply for adequacy. Whar Searle did, they took great pains to camuflage these shortcomings of the study. As I say filter and just present to the FDA what they wished the FDA to know and they did other terrible things for instance animals would develop tumors while they were under study. Well they would remove these tumors from the animals." ( )

FDA Lead Investigator and Task Force Leader, Phillip Brodsky described the 1975 FDA Task Force members as some of the most experienced drug investigators. He went on to state that he had never seen anything as bad as G.D. Searle's studies (Graves 1984, page S5499 of Congressional Record 1985a).

The report quoted a letter written to G.D. Searle on July 15, 1975 from its consultant in reproduction and tetatology, Dr. Gregory Palmer, in regards to a review of some of G.D. Searle's reproductive studies submitted to the FDA (Gross 1985, page SS19838 of COngressional Record 1985b):

"Even following the track you did, it seems to me you have only confounded the issue by a series of studies most of which have severe design deficiencies or obvious lack of expertise in animal management. Because of these twin factors, all the careful and detailed examination of fetuses, all the writing, summarization and resummarization is of little avail because of the shaky foundation."

G.D. Searle officials noted that Dr. Palmer did not look at all of the teratology studies (Searle 1976b, page 21). However, there is no credible evidence that would lead a reasonable person to believe that the studies which were not presented to Dr. Palmer were much better. In fact, the evidence shows that it is very likely that all of the studies were abyssmal.

The FDA Commissioner at eh time, Alexander Schmidt stated (Graves 1984, page S5497 of Congressional Record l985a):

"(Searle's studies were incredibly sloppy science. What we discovered was reprehensible."

Dr. Marvin Legator, professor and director of environmental toxicology at the University of Texas and the pioneer of mutagenicity testing at the FDA from 1962 to 1972 was asked by Common Cause Magazine to review the FDA investigation results of G.D. Searle's tests (Graves 1984, page S5498 of COngressional Record l985a):

"All tests were scientifically irresponsible and disgraceful. I'm just shocked that that kind of sloppy work would even be sent to FDA, and that the FDA administrators accepted it. There is no reason why these tests couldn't have been carried out correctly. It's not that we are talking about some great scientific breakthrough in methodology."

Senator Edward Kennedy at the April 8, l976 hearings before the Senate Subcommittee on Labor and Public Welfare stated (Kennedy 1976): "The extensive nature of the almost unbelievable range of abuses discovered by the FDA on several major Searle products is profoundly disturbing."

In January, 1976, G.D. Searle defended their results by claiming (Searle 1976a, page 5-6):

"In all of the studies at Searle which have been examined by the FDA in its investigation, the scope of the material being considered included seven years of observation, from 1986 to date, in 57 studies involving more than 5,700 animals with over 228 million observations and calculations."

However, their deliberate misconduct and "lies" (as put by FDA Investigator, Dr. Adrian Gross) invalidated their experiments for the following reasons:

1. Many of the problems with the studies included horrendous experimental designs, questions regarding dosage given, loss of animal tissue and data, etc., which invalidates entire experiments and causes what they claim to be 4 million observations and calculations per study (average) to become irrelevant.

2. Only the key aspartame studies were looked at. It is almost a certainty that the non-key aspartame studies were equally flawed. Therefore, this would invalidate the "Hundreds of Millions" of observations and calculating made during these studies.

3. The difference between a study showing no statistical difference and a significant statistical difference is often only a few observations or calculaations.

Therefore, had the myriad of other serious experimental errors not occured (as detailed above), the observation and calculation mistakes in each experiment investigated would, by themselves, invalidate most of the key studies.

4. It is highly unlikely that the FDA Investigation teams found all of the problems with G.D. Searle seemed so intent on covering up their misconduct, that it is quite likely that they were able to hide many of the problems from the FDA.

A series of poorly conceived, flawed studies funded by G.D. Searle were published in Volume 2 (1976) of the Journal of Toxicology and Environmental Health. An Associate Editor of this scientific journal was Robert G. McConnell, the Director of G.D. Searle's Department of Pathology and Toxicology (the department responsible for monitoring the quality of G.D. Searle's pre-approval tests investigated by the 1975 FDA Task Force). Mr. McConnell's story continues later in l977. Another G.D. Searle employee, Carl R. Mackerer was an editor of the journal. Another editor of the journal was Thomas R. Tephly, the person responsible for conducting a series of badly flawed blood methanol and formate measurements in NutraSweet-funded studies over the last 15 years.

In July 1976, the FDA decided to investigate 15 key aspartame studies submitted by G.D. Searle in which the 1975 FDA Task Force discovered problems. Three (3) of the studies were investigated at the FDA (ES, E 77/78, E89) by a 5-member

Task Force headed by FDA veteran Inspector, Jerome Bressler (Graves 1984,

page S5499 of Congressional Record l985a: Gordon 1987, page 497 of US Senate 1987; Farber 1989, page 110).

On August 4, l976, G.D. Searle representatives met with the FDA and convinced them to allow G.D. Searle to hire a private agency, University Associated for Education in Pathology (UAREP), and pay them $500,000 to "validate" the

other 12 studies (Gordon 1987 page 498 of US Senate 1987) ( ).

According the FDA Commissioner during the early 1980's, Arthur Hull Hayes, the UAREP investigation was to "make sure that the studies were actually conducted."

As described by Florence Graves (1984, page S5500 of Congressional Record 1985a):

"The pathologists were specifically told that they were not to make a judgment about aspartame's safety or to look at the designs of the tests. WHy did the FDA choose to have pathologists conduct an investigaton when even some FDA officials acknowldeged at the time that UAREP had a limited task which would only partially shed light on the validity of Searle's testing? The answer is not clear.

"Dr. Kenneth Endicott, Director of UAREP, said in an interview that the FDA had 'reasons to suspect' that Searle's tests 'were no entirely honest.' Because the FDA 'had doubts about (Searle's) veracity,' Edicott said, officials wanted UAREP 'to determine whether the reperts were accurate.'

"FDA scientist Dr. Adrian Gross, in a letter to an FDA oficial, said, 'speaking as a pathologist, it seemed questonalbe that the group could do the kind of comprehensive investigation that was required. He pointed in particular to a variety of issues that needed to be investigated. He said some of these would involve closely questioning administrators and lab technicians about their practices. Since many important issues that should be investigated 'have nothing to do with pathology' he said, only trained FDA investigators were qualified to do a comprehensive evaluation of the testing..

"Meanwhile, an interview with Endicott indicates that Adrian Gross was right: the

pathologists couldn''t--and didn't--carry out a comprhensive review... As former FDA Commissioner Aleander Schmidt put it in a recent interview, UAREF looked at ehe slides to determine whether they had been misrepresented, but didn't look at the conduct of the experiments in depth. The 1975 (FDA) Task Force investigation looked at the conduct of the experiments in depth, but did not look at the alides... Endicott agreed.... 'We could only look at what was there-the tissues.'

The findings of this investigation were released in the Bressler Report in August

1977 (see below).

1977 Donald Rumsfeld, who was a former member of the U.S. Congress and the Chief of Staff in the GErald FOrd Administration, was hired as G.D. Searle's Presidnet. Attorney James Turner, Esq. alledged that G.d. Searle hired Rumsfeld to handle aspartame approval difficulties as a "legal problem rather than a scientific problem." (Gordon 1987, page 497 of US Senate 1987).

( )

As layed out by Mary Nash Stoddard (Stoddard 1995a, page 11), Rumsfeld hired:

John Robson as Executive Vice Presidnet. He was a former lawyer with Sidley and Audtin, Searle's Law Firm and also served as chairman of the Civil Aeronautics Board, which was then connected to the Department of Transportation.

Robert Shapiro as General Counsel. He is now head of Searl's Nutrasweet Division. He had been Robson's Special Assistant at the Department of Transportation ( )

William Greener, Jr., as Chief Spokesman. He was a former splkesman in the (gerald) Ford White House.

Donald Rumsfeld is now on the Board of Directors of the Chicago Tribune which recently wrote a glowing article about the Nutrasweet Company (Millman 1995, Mullarkey 1995).

On January 10, 1977, Fda Chief Counsel Richard Merrill recommended to U.S. Attorney Sam Skinner in a 33-page letter detailing violations of the law that a grand jury be set up to investigate G.d. searle. In the letter, Merrill stated (Merrill 1977, page S10827 of Congressional Record 1985b):

"We requesst that your office convene a Grand Jury investigation into apparent violation of the Federal Food, Drug, and Cosmetic Act, 21 U.S..C. 331(e), and the False Reports to the Government Act, 18 U.S.C. 1001, by G.D. Searle and Company and three of its responsible officers for their willful and knowing failure to make reports to the Food and Drug Administration required by the Act, 21 U.S.C 355 (i), and for concealing material facts and making false statements in reports of animal studies conducted to establish the safety of the drug Aldactone and the food additive Aspartame." ( )

(o.k. we are half way through the history, time for a break.)

[jat]

History of aspartame continued:

All of the G.D. Searle studies were abyssmal as discussed earlier. However, there were two studies where the violatons of the law appeared to be especially flagrant.

The two studies cied by Merrill were the 52-week toxicity study on infant monkeys performed by Dr. Waisman which G.D. Searle with held key information from the FDA and the 46-week toxicity study of hamsters where G.D. Searle had taken blood from healthy animals at the 26th week and claimed that the tests had actualy been performed at the 38th week. Many of the animal from which G.D. Searle claimed had blood drawn from were actually dead at the 38th week.

(See earlier discussion for references). ( )

On January 26, 1977, G.D. Searle's law firm, Sidley & Austin, requested a meeting with U.S. Attorney Samuel Skinner before a grand jury is convened (Gordon

1987 page 497 of US Senate 1987, Mullarkey 1994b, page 6-7). One representative

of Sidley & Austin at that meeting was Newton Minow who is currently on the Board of Directors at the Chicago Tribune ( ) (Gorden 1987, page 497 of US Senate 1987)

On March 8, 1977, in a confidential memo to aides, while he was supposed to be pushing for fraud indictments against G.D. Searle, U.S. Attorney Samuel Skinner

stated that he had begun preliminary employment discussions with G.D. Searle's

law firm Sidley & Austin (Gordon 1987, page 497 of US Senate 1987; Mullarkdy 1994b, page 7).( )

On April 13, 1977, a U.S. Justice Department urged U.S. Attorney Samuel Skinner to proceed with grand jury investigations of G.D. Searle. THe memo points out that the statue of limitations on prosecution would run out shortly (October 10. 1977 for the Waisman monkey study and December 8, 1977 for the hamster study) (Mullarkey 1994b, page 7).

Samuel Skinner withdrew from the G.D. Searle case and Assistant U.S. Attorney William Conlon was then assigned to the Grand Jury Investigation (Gordon 1987,

page 497 of US Senate 1987)

On July 1, 1977, U.S. Attorney Ssamuel Skinner left his job to work for the

G.D. Searle law firm Sidley & Austin. ( ) Thomas Sullivan was apointed

as Samuel Skinner's successor (Gordon 1987, page 497 of US Senate 1987)

Assistant U.S. Attorney William Conlon convened a grand jury, but he let the Statue of Limitations run out on the aspartame charges (Gordon 1987, page 497 of US Senate 1987). Fifteen months later, Conlon accepted a job with the law

firm representing G.D. Searle, Sidley & Austin ( ).

(Gordon 1987, page 497 of US Senate 1987).

Robert McConnell was the Director of G.D. Searle's Department of Pathology and Toxicology which oversaw most of the aspartame research. Mr. McConnell was named to Richard Merrill's attorney, his client was awarded $15,000 bonus and

asked to take a 3-year sabatical (for which he received $60,000/year) because he was a "political liability." (Gordon 1987, page 496 of US Senate 1987)

Philip Brodsky, the Lead Investigator for the original FDA Task Force looking into G.D. Searle's studies retired. He stated that his reason for retiring was the disclosure of the 1975 FDA Task Force findings before the U.S. Congress (Senator

Kennedy hearings in 1976) had become "politicized." As Gregory Gordon put it in the UPI Investigative article (Gordon 1987, page 496 of US Senate 1987):

"He said the main witness, Searle executives and top FDA officials uninvolved in the investigation gave 'the wrong answers to the wrong questions... THey didn't

even let the experts answer the questions.'"

In August 1977, the Bressler Report pertaining to three key aspartame studies, ES, E77/78 and E89, was released. Some of the findings from the three studies reviewed by the Bressler-led Task Force include (Mullarkey 1994b, page 11, 48;

Farber 1989, page 110-112; Verrett 1987, page 385 of US Senate 1987):

a. In one study, 98 of the 196 aimals died but were not autopsied until as much as

one year later. Because of the delay, much of the animal tissues could not be used and at least 20 aimals had to be excluded from postmortem examinations.

b. The original pathology sheets and the pathology sheets submitted to the FDA showed differences for 30 animals.

c. One animal was reported alive at week 88, dead from week 92 through week 104, alive at week 108, and finally dead at week 112. ( )

d. An outbreak of an infectious disease was not reported to the FDA.

e. Tissue from some animals were noted to be unavailable for analysis on the pathology sheets, yet results from an anlysis of this "unavailable" tissue was submitted to the FDA>

f. There was evidence that the diet mix was not homogeneous allowing the animals

to eat around the test substance. This evidence included a picture and statements

by a lab technician.

g. Fifteen fetuses from animals in one experiement were missing.

h. Sections from the animals were too thick for examinaton.

i. There was no documentation on the age or source of the test animals.

j. There was no protocol until one of the studies was well undeway.

k. Animals were not permanently tagged to prevent mixups.

l. SOme laboratory methods were changed during the study, but not documented.

A G.D. Searle pathologist referring to the DKP study was quoted by investigators

as saying (Graves 1984, page S5500 of COngressional Record 1985a):

"You should have seen things when this study was run-- there were five studies being run at one time--things were a mess!"

The leader of the Task FOrce, Jerome Bressler, was quoted as saying (Gordon 1987, page 497 of US Senate 1987):

"The question you have got to ask yourself is: Because of the importance of this study, why wasn't greater care taken? The study is highly questionable because of our findings. Why didn't Searle, with their scientists, closely evaluate this, knowing fully well that the whole society, from the youngest to the elderly, from the sick to the unsick..will have access to this product." ( )

Immediately after the Bressler Report was released, H.R. Roberts, Director

of the FDA's Bureau of FOods created a 5 person task force to review the Bressler Report. This review was done by a team at the Center for Food Safety and Applied Nutrition (CFSAN report). H.R. Roberts would leave the FDA to become

a vice president of the National Soft Drink Association in 1978. ( )

FDA Toxicologist, Jacqueline Verrett was appointed the Senior Scientist of the Bureau of Foods Task Force.

On September 28, 1977, H.R> Roberts, Director of the FDA's Bureau of Foods

received a report from a Bureau of Foods Task FOrce which claimed that G.D. Searle's studies reviewed appeared to be authentic (Meaning that they wer actually conducted) (Mullarkey 1994b, page 8).

For each of the discrepancies found by the Bressler-led Task Force--those listed above and many others -- there was a comment in the FDA Bureau of Foods Report minimizing the problem. It seemed that no matter how serious the mistakes were, the FDA Bureau of Foods was determined to accept the studies by G.D. Searle.

The experimental errors as described above were so bad that it proved difficult to minimize all of the major errors in these key studies. In some cases, the best that the CFSAN could do was to say that "The Task FOrce could find no evidence that this was a deliberate attempt to influence the study." or "It could not be determined if the results would have been altered.." (Farber 1989, page 111, GAO 1987, Appendix 1V).

The Senior Scientist of the FDA Bureau of FOods Task FOrce, Jacqueline Verrett had left the FDA when she openly discussed the Task Force with UPI Investigative Reporter, Gregory Gordon (Gordon 1987, page 497 of the US Senate 1987):

"Jacqueline Verrett, the senior scientist on the review team, said members were barred from stating opinions about the research quality. 'It seemed pretty obvious that somewhere along that line they (bureau officials) were working up to a whitewash,' she said. 'I seriously thought of just walking off that task force.'

Verrett, now a private consultant, said that she and other members wanted to 'just

come out and say that this whole experiment was a disaster and should be disregarded.'( )

In her testimony befor the U.S. Senate, Dr. Verrett stated the following (Verrett 1987):

"This authentication was hence intended to verify that the submitted data had not been altered; that it reflected the actual outcome of the study, and that it did not change substantially, particularly in a statistical sense, the various parameters from

which the conclusion of safety had been derived.

"Our analysis of the data in this manner revealed that in these three studies, there were really no substantial changes that resulted, although in numerous instances, a definitve answer could not be arrived at because of the basic inadequacies and improper procedure used in the execution of these studies.

"I would like to emphasize the point that we were specifically instructed not to be concerned with, or to comment upon, the overall validity of the study. This was to be done in a subsequent review, carried out at a higher level. ( ...)

"It would appear that the safety of aspartame and its breakdown products has still not been satisfactorily determined, since many of the flaws cited in these studies were also present in all of the other studies submitted by Searle. ( ...)

"Well, they told us in on uncertain terms that we were not to comment on the validity of it. And I hoped, although having been there at that point for 19 years, I

should have known better, that there really would be an objective evaluation of this beyond the evaluation we did. ( )

"I do not feel that that was done, based on what I hav read in the GAO report that I

have looked at and so forth. They definately did not objectively evaluate these studies, and I really thinkit should have been thrown out from day one.

"We were looking at a lot of little details and easy parameters in this study, when the foundation of the study, the diet and all of these other things, were worthless.

We were talking about the jockey when we should have been talking about the horse, that he had weak legs. It is built on a foundation of sand."

2 to 3 more posts to go on this one point.

[QuinaQuen]

Did I miss a post? Last time I checked, aspartame always come in blue packets. The pink ones are saccharine. Even the knockoffs and store brands stick to this formula.

[jat]

Yes, I made a mistake, and you can't erase the topic message or change it.

[rancho_gordo]

I know a few people who use the little packets and I find they often have an off sense of what is sweet and what is not.

I have one friend who drinks GALLONS of Diet Coke but reacts with disdain if offered a Diet pepsi, as if it were made with dingleberries. I think they all taste nasty.

Outside of diabetics, can a little sugar be worse than these chemical sweeteners? How much sugar does one need to consume?

For the record, I did try a soda with Splenda and it wasn't spendid. There was a distinct aftertaste.

[jat]

Aspartame History and Research Info.

The FDA general counsel wrote a letter to Consumer Attorney, James Turner,

Esq. respponding to Mr. TUrner's concern about the quality and validity of G.D. Searle's experiments. The FDA stated, "THe Public Board of Inquiry on aspartame should provide a vehicle for definitive resolution, at least for those studies about which you are most concerned." (Graves 1984, page S5498 of Congressional Record 1985a). As will be discussed later, Dr. John Olney and James Turner, Esq. were not allowed to have the quality and validity of the G.D. Searle studies considered at the Public Board of Inquiry.

1978. On December 13, 1978, UAREP submitted its results of their analysis of 12 of G.D. Searle's aspartame studies. UAREP stated in their report that "no discrepancies in any of the sponsor's reports that were of sufficient magnitude or nature that would comprise that data originally submitted." (Farber 1989, page 33)

Remember, the Director of UAREP pointed out in an interview that their pathologists did not conduct a comprehensive review of the studies, they only looked at the animal tissues )Graves 1984, page S5500 of Congressional Record 1985a).

As it turns out, UAREP pathologists who examined the test results were discovered to have missed and withheld negative findings from the FDA (Gross 1987b, page 2-5). ( ) In some cases, they completely missed cancerous brain tumors when analyzing the slides. In addition, some of the slides that were to be examined by UAREP pathologists were missing even though they were supposed to have been kept under "FDA seal." ( ) (olney 1987, page 6-7) FDA

toxicologist Adrian Gross stated that the UAREP review "may well be interpreted as nothing short of a whitewash." (Farber 1989, page 114). Given that the UAREP review results was so biased in favor of G.D. Searle, one wonders why the FDA would allow a company being investigated for fraud to pay $500.000.00 and hire an outside company to "validate" their studies. ( )

Even though the UAREP report was biased, there were numerous instances in that report which demonstrated that G.D. Searle had not submitted even marginally accurate findings to the FDA of their pre-approval aspartame tests. For example, in one study, twelve anmals acutally had cancerous brain tumors, yet UAREP

reported to the FDA that only three animals had such tumors ((Gross 1987b, page 3-4). ( )

1979 In March of 1979, the FDA somehow concluded that G.D. Searle's aspartame studies could be accepted. They decide to convene the Public Board of Inquiry (PBOI) which was agreed to by Dr. John Olney and Attorney James Turner more than four years earlier (Federal) Register 1979).

a. Whether the ingestion of aspartame either alone or together with glutamate poses a risk of contributing to mental retardation, brain damage, or undesirable effects on neuroendocrine regulatory systems.

b. Whether the ingestion of aspartame may induce brain neoplasms (tumors) in the rat.

c. Based on answer to the above questions.

(1) Should aspartame be allowed for use in foods, or, instead should approval of aspartame be withdrawn?

(2) If aspartame is allowed for use in foods, i.e. if its approval is not withdrawn, what conditions of use and labeling statemtns should be required, if any?

Dr. John Olney, G.D. Searle, and the FDA's Bureau of Foods were allowed to nominate scientists for the 3-person PBOA panel (Farber 1989, page 34, Federal Register 1981, page 38286).

It is important to note that the scope of the review was very limited in light of all of the various adverse reactions reported to the FDA> THe PBOI also disallowed any discussion of the validity of the pre-approval experiments because it accepted the word of certain FDA officials that these experiments had been "validated." Finally, the PBOI was told not to consider aspartame in beverages, only in dry goods.

In June of 1979, the acting FDA Commissioner, Sherwin Gardner selected the 3-person Public Board of Inquiry. THe panelists were Peter J. Lampert, M.D., Professor and Chairman, Department of Pathology, University of California (San DIego), Vernon R. Young, PH.D. Professor of Nutritional Biochemistry, MIT., and Walle Nauta, M.D., Ph.D., Institute Professor, Department of Psychology and Brain Science, M.I.T.

Dr. John Olney strongly objected to the COmmissioner's selection of one of the panelists, Dr. Vernon Young, on grounds of conflict of interest and lack of qualifications (Olney 1987, page 3). Dr. Young had written nonaspartame-related articles in collaboration with G.D. Searle's scientists (Brannigan 1983, page 196). In addition, Dr. Olney stated that the question of aspartic acid's neurotoxicity should be looked at by a neuropathologist and that Dr. Young was unqualified since his field was Nutritiion and Metabolism. Dr. Olney's objections were over ruled by acting FDA COmmissioner Sherwin Gardner and the panelists who he objected to was assigned to study the issue of aspartic acid toxicity.

One of the PBOI members, Dr. Walle Nauta stated (Graves 1984, page S5498 of COngressional Record 1985a):

"It was a shocking story we were told about Searle's animal testing but, there was no way we could go after it. We had absolutely no way of knowing who was tight. We had to take the FDA's word."

Dr. Nauta stated that he would have "definately" considered other tests and factors if he had known that aspartame was planned for use in soft drinks (graves 1984, page S5503 of Congressional Record 1985a).

1980 The Public Board of Inquiry voted unanimously to reject the use of aspartame until additional studies on aspartame's potential to cause brain tumors could be done. The PBOI was particularly concerned about experiment E33/34 where 320 rats recieved aspartame and a much higher percentage of animals in the aspartame group developed tumors than in the control group (Brannigan 1983, page 196). In addition, the PBOI was concerned about experiment E70 where 80 rats recieved aspartame. Both the aspartame group and the control group had an

unusually high number of tumors, leading one to suspect that both groups were actually given aspartame (federal register 1981).

The PBOI did not believe that aspartic acid presented a neurotoxic hazard. Yet Dr. Olney pointed out that (Olney 1987, page 3):

"(Dr. Young had a) lack of qualification" and that he "based his decision on a consideration of (aspartic acid) alone without regard to the real issue, i.e. is it safe to add (aspartic acid) to the large amountsof (glutamic acid) that are already adultering the food supply?"

In addition, the "conservative" safety plasma level of aspartic acid used by Dr. Young was the level at which half the animals developed brain damage (Brannigan 1983, page 197). These errors by Dr. Young throw the question of safety of asparti acid as part of aspartame into doubt. We will address this issue in more detail in a later section.

1981 On January 21, 1981, the day after Ronald Reagan takes office as U.S. Presidnet, G.D. Searle reapplied for the approval of aspartame. G.D. Searle reaplied for the approval of aspartmae. G.d. Searle submits several new studies along with their aplicaton. It was believed that Reagan would certainly replace Jere Goyan, the FDA Commissioner. G.D. Searle president, Donald Rumsfeld's connections to the Republican party were also thought to play a part in Searle's decision to reapply for aspartame's approval on the day after Ronald Reagan was inaugurated (Gordon 1987, page 499 of US Senate 1987). ( )

According to a former G.D. Searle salesperson, Patty Wood-Allott, G.D. Searle presidnet, Donald Rumsfeld told his salesforce that, if necessary, "he would call in all his markers and that no matter what, he would see to it that aspartame would be approved that year." (Gordon 1987, page 499 of US Senate 1987)

In March of 1981, a 5-member panel of scientists was established by the FDA Commissioner Jere Goyan to review the issues raised by the PBOI (Gordon 1987, page 498 of US Senate 1987; Mullarkey 1994b, page 8).

In April 1981, Arthur Hull Hayes, Jr. was appointed FDA Commissioner by Ronald Reagan (Graves 1984, page S5502 of COngressional Record 1985a),

On May 18, 1981, three of the scientists in the 5-member panel sent a letter to the panel lawyer, Joseph Levitt discussing their concerns about aspartame. Those three scientists were Satva Dubey (FDA Chief of Statistical Evaluation Branch), Douglas Park (Staff Science Advisor. and Robert Condon (Veterinary Medicine). Dubey thought that the brain tumor data was so "worrisoome" in one study that he could not recommend approval of aspartame (Gordon 1987, page 495 of US Senate 1987). In another study, Dubey said that key data appeared to have been altered (Gordon 1987, page 499 of US Senate 1987).

In his UPI Investigation, Gregory Gordon went on to describe the unusual events that followed (Gordon 1987, page 499 of US Senate 1987):

To be continued...

[Pan]

jat, I'm waiting for something in your chronology that takes place in the last 10 years or so.

[jat]

Pan, First I'm trying to show the approval process for aspartame, which gets

more interesting. This is only about the history. I feel it is significant.

In 1996 Neuroscientist Dr. John W. Olney, publishes research showing that aspartame may be a brain tumor agent. He shows that aspartame caused brain cancer in preapproval research, that a breakdown product of aspartame has caused mutations in vitro, and that from 4 to 13 years after approval there was a

significant increase in the conversion of less deadly brain tumors to much more deadly brain tumors in susceptible populations.

I need to go to the Library to find the scientific reports, right now with my knee, I

can't walk much. They will be forthcoming. One more month to go? We'll see.

Edited for references:

Olney, John W., Nuri Farber, Edward Spitznagel, Lee Robins, 1996. "Increasing Brain Tumor Rates: Is There a Link to Aspartame?" Journal of Neuropathology and Experimenal Neurology, Volume 55, No. 11, Page 1115-1123.

Dr. John Olney, from Washington University School of Medicine, has other studies

from earlier dates.

Years ago, I read the actual scientific studies showing DNA changes and personality changes in a Medical Journal that I found quite by accident.

My initial purpose was to suggest healthier forms of sweetener, and I do feel all

that is needed is more labeling on the sweeteners, like cigarettes. Though I

don't expect this post to change the initial comments of some, I didn't appreciate

the TONE of the words. And I do care for people so it didn't suit my conscience to

not post a little evidence, but I think most people are aware of the sweetener

hazards. A lot depends on the amount one consumes.

I really would have liked to just go to the lap top and post a few light topics and

recipes to unwind. I can do this but I have other things I need to do right now.

That's why I will only be doing recipes in the future. Jennifer

Edited January 23, 2004 by jat (log)