FDA Proves Aspartame Studies Flawed

Yes, you read right – the FDA proved that the original aspartame studies were flawed in numerous ways. They testified in a US Senate hearing that GD Searle submitted falsified research results.

This was in 1977, and we are still waiting for them to do something about it. I wonder why it’s taking so long?

On Our Side In The ’70s

Let me get you up to date  …. in the 1970s, the FDA actually tried to protect the consumer. The following comes directly from FDA files and from US Congressional Records:

FDA Lead Investigator and Task Force Team Leader, Phillip Brodsky described the 1975 FDA Task Force members investigating the safety of aspartame 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 teratology, Dr. Gregory Palmer, in regard to a review of some of G.D. Searle’s reproductive studies submitted to the FDA (Gross 1985, page S10838 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.”

GD Searle Lied To FDA

After investigating the first FDA approval request for aspartame, FDA Toxicologist and Task Force member, Dr. Adrian Gross stated (Wilson 1985):

“They [G.D. Searle] lied and they didn’t submit the real nature of their observations because if they had done that, it is more than likely that a great number of these studies would have been rejected simply for inadequacy. Searle took great pains to camouflage these shortcomings of the study. As I say, they filtered and just presented 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 Proves Aspartame Studies Flawed

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

Below is a preliminary statement before the US Senate about the breadth of this investigation from FDA Toxicologist and Task Force team member, Dr. Andrian Gross (Gross 1987a, page 1-2):

“… the set of all such studies executed by that firm from about 1968 to the mid-1970’s 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 audited in 1975 (whether they had references to aspartame or to any of the six drug products of Searle’s) and, by extension, to the totality of experimental studies carried out by that firm around that time — 1968 to 1975.”

The FDA Task Force concluded (Gross 1987a, page 2-3):

“At the heart of 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) GD Searle Company, we have no basis for such reliance now.

“We have noted that Searle has not submitted all the facts of experiments to the 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 health 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 true 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.”

FDA Findings

Here are a few of the relevant, yet shocking, findings from FDA and Congressional documents archiving the FDA Task Force Report:

1. Excising masses (tumors) from live animals, in some cases without histological examination of the masses; in others, without reporting them to the FDA. (Schmidt 1976c, page 4 of US Senate 1976b). When questioned about these actions, Searle’s representatives stated, “These masses were in the head and neck areas and prevented the animals from feeding.” (Buzzard 1976a)
2. Failure to report to the FDA all internal tumors present in the experimental rats, e.g., polyps in the uterus, ovary, neoplasm, as well as other lesions. (Gross 1987a, page 8).
3. G.D. Searle stored animal tissues in formaldehyde for so long that they deteriorated. (Gordon 1987, page 496 of US Senate 1987; US Schmidt 1976c, page 25, 27 of US Senate 1976b)
4. Instead of performing autopsies on Rhesus monkeys that suffered seizures after being fed aspartame, the company financed a new monkey seizure study with a different methodology that showed no problems. (Gordon 1987, page 496 of US Senate 1987)
5. Reporting animals as unavailable for necropsy when, in fact, records indicate that the animals were available, but Searle choose not to purchase them. (Schmidt 1976c, page 5 of US Senate 1976b)
6. Animals that had died were sometimes recorded as being alive and visa 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)
7. 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)
8. G.D. Searle told the FDA that 12 lots of DKP were manufactured and tested in one study, yet only seven batches were actually made. (Gross 1985, page S10835)
9.  Significant deviations from the protocols of several studies were noted, which may have compromised the value of these studies . . . In the Aspartame 52 weeks Monkey Study, the protocol was written after the study had been initiated. (Gross 1985, page S10835)
10. 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 cottontail 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 certainly must have 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 Nutrition could never determine how that was possible. (Stoddard 1995a, page 9; Graves 1984, page S5500 of Congressional Record 1985a)
11. 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)
12. 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, and adding adverse pathology reports on the same slide. (Schmidt 1976c, page 4-5 of US Senate 1976b)
13. Animals were not removed from the room during the twice per month exterminator sprayings. (Gross 1985, page S10836 of Congressional Record 1985b)
14. Often the substance being tested, which was given to the 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 were not maintained. (Gross 1985, page S10836 of Congressional Record 1985b)
15. In the Aspartame (DKP) 115 week rat study, the written observations of the pathology report was changed by the supervising pathologist, Dr. Rudolph Stejskal, even though he was not physically present 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)
16. Contrary to protocol, slides were not prepared of (unusual) lesions from the Aspartame (DKP study) tissue for microscopic examinations. (Gross 1985, page S10837 of Congressional Record 1985b)
17. 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 1985b)
18. 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 in computing group means (which were reported to the FDA). It is not clear what criteria may have been used for selecting a portion of the data or for deleting the others in computing the means (reported to the FDA). (Gross 1985, page S10838 of Congressional Record 1985b)
19. 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)
20. There were clerical or arithmetic errors, which resulted in reports of fewer tumors. (Schmidt 1976c, page 27 of US Senate 1976b)
21. G.D. Searle delayed the reporting of alarming findings. (Schmidt 1976c, page 27 of US Senate 1976b)

OK FDA, we’re waiting!