FDA and NIH Disappoint on Sweetener Safety

By Myra L. Karstadt, Ph.D
 
Did you enjoy your acesulfame today?  How much did you eat?  Do you know whether acesulfame is safe to eat?

 Those are not trick questions.  Acesulfame is currently one of the best-selling artificial sweeteners in America, but it’s likely that very few people even know that acesulfame is in many of their foods and beverages. 

The FDA has approved acesulfame as a food additive, but it based its decision on flawed studies.

Stealth Sweetener
There’s a good reason why acesulfame has such a low profile: it’s usually a back-up player, used in sweetener blends with other artificial sweeteners.  Most frequently, you’ll encounter acesulfame in blends with sucralose (Splenda), the #1 artificial sweetener in the country. 

When you see “Sweetened with Splenda” on the front of a package of processed food, take a look at the ingredients list on the back of the package.  Most likely, before or after sucralose you’ll see an entry for acesulfame or acesulfame potassium (the longer name for the chemical).  Ingredients are listed in descending order of amount in a product, and artificial sweeteners such as sucralose, acesulfame and aspartame usually appear way down towards the end of the ingredient listings.  That’s because you don’t need much “high-intensity” artificial sweetener:  acesulfame is approximately 200 times sweeter than sugar, while sucralose is approximately 600 times sweeter than sugar.

The range of products in which acesulfame appears is very wide; some products are listed in Table I.  Many diet sodas contain acesulfame, in blends with either aspartame or sucralose. The product range is so wide because, unlike some other artificial sweeteners such as aspartame, acesulfame and sucralose are stable to heat and cold.  Also, acesulfame is said to create what is claimed to be a better-balanced sweet taste than you would get with Splenda or aspartame alone.

Table 1: Some processed food products containing acesulfame*

 

Product

December 2005

September 2008

Jell-O gelatin, sugar free

aspartame, acesulfame

aspartame, acesulfame

Murray cookies, sugar free

sorbitol, sucralose, acesulfame

acesulfame, sucralose

4C Totally Light, naturally decaffeinated, natural lemon flavor

sucralose, acesulfame

acesulfame, sucralose

Kool-Aid, sugar free

aspartame, acesulfame

aspartame, acesulfame

Ocean Spray Light/ Diet Ocean Spray Cranberry

acesulfame, sucralose

acesulfame, sucralose

Breyer’s, no sugar added, Double Churn

sucralose, acesulfame

sucralose, acesulfame

Swiss Mix cocoa mix

Splenda, acesulfame (Diet with calcium)

acesulfame, sucralose (Sensible Secrets Diet 25 calories

The one product where acesulfame takes a starring role is Domino Pure D’Lite, a baking blend which combines sugar with three sweeteners: acesulfame, maltodextrin (a derivative of corn or wheat), neotame (a modified aspartame reported to be approximately 8000 times sweeter than sugar).  Consumer Reports recently rated the Domino baking product better for baking than the Splenda baking blend. (1). (The reason the Domino product contains acesulfame is that Domino, although probably the best-known brand sugar, couldn’t use sucralose in its baking blend because of exclusivity agreements between Tate & Lyell, the producer of sucralose, and a Johnson & Johnson subsidiary which markets Splenda products in the U.S.)

Concerns About Acesulfame
Acesulfame was never demonstrated to be non-carcinogenic and FDA should not have approved it for use as a food additive. Food additives such as acesulfame are required to be pre-cleared for safety before an additive is marketed.  In addition, the Delaney Clause still applies to food additives, so if a food additive is carcinogenic and will appear in foods consumed by people, it cannot be approved. 

The long-term animal test data purporting to show acesulfame’s safety, specifically as regards cancer potential, are deeply flawed.

The animal tests on acesulfame were carried out in the mid-1970s, a period when  standards and procedures for animal carcinogenicity tests were being developed.  Science staff at FDA who reviewed the tests of acesulfame in the 1980s noted that: “[the] question remains whether these studies are sufficiently definitive or rigorous in light of the potential for widespread, high exposure to acesulfame potassium in all group [sic] in the population.” (2).

What was wrong with the tests?  They were poorly designed, badly executed, and data from the studies weren’t analyzed properly.  Way back in the early 1980s, FDA could and should have required new good tests in rats and mice.

Unfortunately, instead of requiring that Hoechst, which manufactures acesulfame,  do new good tests, FDA let Hoechst discard a study carried out in rats whose results suggested acesulfame caused cancer, and carry out a redo of pathology for a second study in rats where there were insufficient numbers of tissues collected for evaluation.  The one study carried out in mice went on for 80 rather than 104 weeks, the standard length of long-term animal studies. Eighty weeks may not have been sufficient to detect cancers caused by acesulfame exposure.

In 1988, FDA approved Hoechst’s food additive petition (FAP) for use of acesulfame in some dry products and formulations. (3). That initial approval, which okayed  Hoechst’s test data, has been used by FDA as the basis for subsequent food additive approvals.

Flawed Tests – and Flawed Conclusion
The “big kahuna” in the artificial sweeteners world is soda.  (These days, soda consumption seems to be down from where it was in say, 1990, but artificially sweetened flavored water, energy drinks, and fruit drinks have provided new and/or increased opportunities for use of acesulfame.)

In 1996, FDA was considering a food additive petition (FAP) for use of acesulfame in soda. The Center for Science in the Public Interest (CSPI) had filed repeated objections to FDA’s approvals of acesulfame. It was clear that FDA, which had blown off CSPI’s objections to previous food additive approvals for acesulfame, wouldn’t be swayed from approving acesulfame use in soda.  However, there was a possible route to slowing the approval: getting good tests of acesulfame done by the National Toxicology Program (NTP).

NTP is the federal government’s toxicology testing agency.  NTP is an inter-agency organization, with FDA among the agencies that can nominate chemicals for testing and, it seems, veto nominations for testing made by other agencies or members of the public.  NTP developed the methodology for two-year bioassays in rats and mice, and that standardized methodology is often referred to as the “gold standard” for long-term animal testing.

In 1996, CSPI, where I was then working on acesulfame, nominated the sweetener for long-term testing by NTP in the standard two-year bioassay.  Looking at the methodology of the 1970s Hoechst tests and NTP’s “gold standard bioassays,” it’s obvious that the methodologies have little in common. There were all sorts of errors in design and implementation of the Hoechst tests related to selection of test animals, animal husbandry, selection of maximum tolerated dose (MTD), length of time animals were kept on test, and collection of tissues for study by gross and microscopic pathology.  The NTP test design was “gold,” while Hoechst’s tests looked like they had been designed by Mel Brooks.

What happened to the CSPI nomination?  The CSPI nomination was rejected even though It would have been obvious to NTP staff that the Hoechst tests were not adequate.

Although CSPI’s nomination for testing of acesulfame in the bioassay program was rejected, FDA and NTP did decide to do a study in which test animals would be treated with acesulfame.  According to Dr. Sam Wilson, Acting Director of the National Institute of Environmental Health Sciences (the parent organization of NTP): “NTP carefully reviewed the CSPI’s 1996 nomination for carcinogenicity testing of acesulfame.  In response to this nomination, the NTP carried out toxicology studies in genetically modified mice……”  (4).

Unfortunately, the GMM (genetically modified mice) strains selected for the study were known to be insensitive to chemicals like acesulfame, which are not genotoxic (interacting directly with the constituent bases of DNA).  Those studies were meaningless as regards potential carcinogenicity of acesulfame, although they did provide confirmation that acesulfame would not have any effect on the insensitive mice. NTP announced their negative test results in 2003, concluding that acesulfame hadn’t caused cancer in the GMM. The published version of the GMM test results, which came out in 2005, did note that test animals’ insensitivity to the test compound would be a possible reason for negative results.

After completion of the GMM studies of acesulfame, the meaningless negative results were then drawn on by FDA and NTP to support their conclusion that long-term bioassay of acesulfame wasn’t necessary.  According to Dr. Wilson: “Based upon the findings from the [GMM] studies and in consultation with FDA, it was determined that additional testing of acesulfame was not warranted at that time.” (5).

That’s exactly the opposite of the correct conclusion: negative results likely linked to the GMM insensitivity to acesulfame didn’t give any insights into whether or not acesulfame caused cancer in animals. Long-term tests were needed to clear that up.                          

In mid-1998, FDA approved acesulfame for use in soda.  A few sodas containing acesulfame, usually in combination with aspartame, went onto the market, but it wasn’t until sucralose (approved for general use in food in 2002) zoomed in popularity that acesulfame’s own sales took off.

Still Awaiting Better Testing
By 2006, “Sweetened with Splenda” processed foods with acesulfame as a “stealth sweetener” were all over the supermarket shelves.  I became concerned about the sudden increase in acesulfame use, and that year I filed FOIAs with NIEHS to obtain documentation of why CSPI’s 1996 nomination of acesulfame had been rejected.  In addition, I published a letter in Environmental Health Perspectives (EHP) (6) expressing my concern about acesulfame’s widespread use without adequate safety testing.  I also nominated acesulfame for testing by NTP.

Once again, the nomination for NTP bioassay of acesulfame was rejected.  Subsequent FOIA attempts by me and by me in cooperation with Dr. Michael F. Jacobson, Executive Director of CSPI, to obtain information on why the 2006 nomination had been rejected, were unsuccessful.  NIH simply stonewalled the FOIA requests.

Finally, I asked my Congressman’s office to send a letter to NTP asking them why they hadn’t been willing to test acesulfame.  I’ve quoted from the NIEHS reply above. The letter to Rep. Van Hollen from Sam Wilson, Acting Director of NIEHS as of mid-2008, makes it clear that FDA didn’t want acesulfame tested and the meaningless GMM tests were selected by NTP with FDA to take the place of bioassays.

So where are we now?  Because acesulfame, unlike saccharin, wasn’t considered carcinogenic by FDA, and the chemical, unlike aspartame, hasn’t been linked with illness in people, there is no warning on a food label to call people’s attention to the presence of acesulfame.  People- and especially children- are consuming, most likely without even being aware of it, a food additive of unknown toxicity.

Millions of people are currently consuming acesulfame. Poor safety tests carried out in the 1970s that were inadequate in the 1980s are certainly inadequate now, given the sweetener’s extensive use.  Good tests of quality consistent with the NTP bioassays are needed, and, if FDA and NTP continue to resist carrying out good tests or ordering the manufacturer to do them, Congress may need to do a review of the activities at FDA in the food additives area in general and acesulfame in particular.

Until the safety of acesulfame is established, it would be wise to follow CSPI’s good advice: avoid foods containing acesulfame. (7).

Myra L. Karstadt, Ph.D is an adjunct assistant professor at Drexel University’s School of Public Health.

References
1. Consumer Reports. 2007.  Sweeteners.  How the brands measure up.  October 2007: 16-17.
Unfortunately, Consumer Reports, with which I have corresponded, has shown little interest in discussing potential carcinogenicity of acesulfame in their articles on artificial sweeteners.

2. Taylor LL. 1986.  Memorandum: Request for CAC Evaluation of the Carcinogenic Potential of Acesulfame K: Update.  U.S. Food and Drug Administration, Additives Evaluation Branch re: Food Additive Petition No. 2A-3659 (June 19, 1986).  This memorandum was obtained from FDA through FOIA.

3. U.S. Food and Drug Administration. 1988.  Press release: Acesulfame Potassium (Sweetner) [sic] Approval.  (July 27, 1988); Food and Drug Administration (1988).  Food additives permitted for direct addition to food for human consumption; Final rule.  53 FR 28379-28383 (July 28,1988).

4. Wilson SH. 2008.  Letter to the Honorable Chris Van Hollen (June 16, 2008).

5. Wilson SH. 2008.  4, supra.

6. Karstadt ML. 2006. Testing needed for acesulfame potassium, an artificial sweetener.  Environ. Health Perspect 114(9): A516 (September 2006). 

7. Schardt D. 2004. Sweet Nothings: Not All Sweeteners are Equal.  Nutrition Action Health Letter (May 2004): 8-11.