I get asked on a regular basis for my opinion on artificial sweeteners and I assume this is no different in your practice. In this issue I will give you information about two of the most popular sweeteners on the market today: sucralose (Splenda®) and aspartame (Equal®, NutraSweet®). I will summarize my thoughts about these sweeteners at the end of this article in the “What To Tell Our Patients” section.

Sucralose (Splenda®)

What is Sucralose?

• Splenda® is the new rave in artificial sweeteners. The marketing campaign for Splenda® has centered around the fact that sucralose, the main ingredient in Splenda®, is made from sugar. So, the marquee of the marketing campaign is “Made from sugar, so it tastes like sugar.” The clear implication is that since sucralose is made from sugar it must be good for you.
• I have read the FDA’s multi-page final ruling for the approval of sucralose and am concerned. If you are interested in reading this report you can access it by going to:



http://www.cfsan.fda.gov/~lrd/fr980403.html



• The first thing to note is that sucralose is not a natural molecule. To be a little more specific about how sucralose is made, 3 hydroxyl (-OH) groups are removed and are unnaturally replaced with chlorine. Sucralose is:



1,6 Dichloro-1,6-dideoxy-ß-D-fructofuranosyl-4-chloro-4-deoxy-ά-D-glactopyranoside



• This man-made molecule falls into the class of chemicals known as chlorinated hydrocarbons. Other chemicals that fall into this same category include many dangerous pesticides like dioxin and DDT. The chlorinated monosaccharide, 6-chloro-6-deoxy-D-glucose is a known neurotoxin. Thus, sucralose falls into a category of molecules that should immediately raise serious questions about potentially deadly health concerns.
• To be fair, however, you need to know that not all chlorinated molecules are toxic to humans. We cannot, in good faith, immediately make the connection that sucralose is a toxin just because it is a chlorinated hydrocarbon. The only way to assess what this new, unnatural molecule will do to humans is to perform studies. Since sucralose has FDA approval, you would assume that these studies had been completed in a sufficient manner. You would also assume that if the studies raised any questions about potential health concerns that the FDA would err on the side of safety and would not approve a questionable chemical as being safe for consumption.

The Testing Of Sucralose

• All of the studies submitted to the FDA for approval were animal studies. The studies submitted by McNeil revealed some very disturbing findings. I will use direct quotes from the FDA Final Report so that you can see exactly what the results were. The partial list of negative findings follows:
• The testing for genotoxicity (cancer potential) revealed:



“...sucralose and its hydrolysis products showed weakly genotoxic responses in some of the genotoxicity tests.”

“Tests for clastogenic (capable of causing breaks in chromosomes) activity of sucralose in a mouse micronucleus test and a chromosomal abberration test in cultured human lymphocytes were inconclusive. Sucralose was weakly mutagenic in a mouse lymphoma mutation assay.”

“Results of three other genotoxic tests were inconclusive: The chromosomal abberration assay in cultured human lymphocytes, the sex-linked recessive lethal assay in Drosophila melangaster, and the covalent DNA binding potential study in rates. 1-6-DCF (a by-product of sucralose) was weakly mutagenic in the Ames Test and the L5178Y TK+/- assay.”



• So, sucralose and its by-products did show genotoxicity. The FDA simply dismissed these findings stating that the 2 year cancer studies done in rats were negative and thus, the findings of genotoxicity were insignificant. In other words, the FDA suggested that since limited tests done in rats did not show any increased cancer rates, the actual finding of genotoxicity should be completely dismissed. And, they were.
• I ask you to consider how cancer develops in humans who are exposed to cancer-causing toxins. Take asbestos exposure for example. When did people exposed to this toxin develop cancer? Did it take months, a couple of years, or many years? The answer is many years. Most people did not develop cancer for over a decade. So, why the FDA simply dismissed numerous findings of genotoxicity through a two-year rat study and concluded that sucralose will not cause cancer in humans in the long-term is puzzling, if not disturbing.
• The testing for immune toxicity revealed that sucralose caused damage to the immune system:



“...when rats were fed sucralose in a 4 to 8 week range finding study the following effects were noted: Decreased thymus and spleen weights , lymphocytopenia , and cortical hypoplacia of the spleen and thymus.”



• In an effort to reduce the negative impact of these findings, McNeil then followed this up with a study that only lasted 28 days. This new study again showed disruptions in immune functions at higher dose sucralose fed rats, but not in lower dose groups. The FDA found this 28 day study to be sufficient in defining the safety of sucralose for dosing in humans to not cause immune function disruptions. The bottom line is that the studies showed that sucralose could have a negative effect on the immune system.
• One of the more disturbing findings revealed through the FDA Final Report concerned the testing to determine the neurotoxicity of sucralose. Remember that sucralose is of the same family of chlorinated hydrocarbons as are many dangerous pesticides. The question of neurotoxicity is a big one.
• McNeil conducted two neurotoxicity studies, one in mice and one in monkeys. The tests were performed for only 21 and 28 days, respectively. Here are the findings as reported by the FDA:



“Animals receiving sucralose or an equimolar mixture of sucralose hydrolysis products...did not exhibit any clinical signs of neurotoxicity. The agency concludes that the lack of neurotoxic effects by both sucralose and its hydrolysis products at the tested dose levels in these studies provides assurance that sucralose used as a food additive under the proposed condition of use will not produce neurotoxic effects.”



• The FDA stated that 28 days of testing in monkeys and mice was enough proof for them that there would not be neurotoxic effects in humans. The important difference is that humans now use sucralose daily for years and years. How in the world would a 28 day study give the FDA enough comfort to make their conclusion that sucralose is not neurotoxic for long-term use by humans?
• Interestingly enough, a 2006 peer-reviewed study in the journal of Headache presented a case study where sucralose was a trigger for migraine headaches (Headache. 2006 Sep,46(8): 1303-4.) As clinicians, this is important information to consider when we go down the causality differential list for headache symptoms.
• Other negative findings dismissed by the FDA final report included:

Aspartame (NutraSweet® or Equal®)

History

• In 1965, the researchers at G.D. Searle were developing a new ulcer medication when they discovered that they had created a substance that was 200 times as sweet as sugar but had no calories. In 1971, Searle labs felt it had sufficient evidence of aspartame safety to approach the FDA for approval. Questions about potential brain lesions, tumors, and endocrine dysfunction delayed approval until 1981.
• The approval of aspartame was marred with questions of scandal. Dr. Adrian Gross, the chief scientist on the FDA task force investigating Searle, told CBS Nightly News in 1981 that Searle took great pains to cover up the shortcomings of their studies, even going as far as to remove tumors that developed in animals during the research in order to mask cancerous evidence. The Public Board of Inquiry (P.B.O.I.) stated in a report dated September 30, 1980:



“On the basis of the conclusion concerning Issue Number 2, the Board concludes that approval of aspartame for the use in foods should be withheld at least until the question concerning it possible oncogenic potential has been resolved by further experiments. The Board has not been presented with proof of reasonable certainty that aspartame is safe for use as a food additive under its intended conditions of use.”



• Despite numerous unanswered questions and contradictory conclusions from various investigations, Commissioner Hayes ignored the recommendations of the FDA’s own P.B.O.I. and approved aspartame for dry use. It was approved for use in liquids in 1983.

What is Aspartame?

• Aspartame is a combination of the amino acids phenylalanine, aspartic acid, and methanol. The worst of these is methanol (wood alcohol). High amounts of methanol alone results in toxicity and blindness. The amounts found in aspartame foods, however, do not have enough methanol to cause this effect.
• The real danger is that methanol is changed to the carcinogen formaldehyde. Formaldehyde has been shown to bind to tissue components in human studies (Trocho, C et al, ‘Formaldehyde derived from dietary aspartame binds to tissue components in vivo’, Life Sciences 1998, 63 (5): 337-349.) I will point out that methanol is found in some of the fruits and vegetables we eat. The difference is that these foods also contain amounts of ethanol which blocks the production of formaldehyde in the body. Aspartame contains no ethanol.

Some Disturbing Facts

• Professor Ralph Walton of Northeastern Ohio University’s College of Medicine conducted a survey of aspartame studies in peer-reviewed medical literature in 1996. Of 166 studies reviewed, 74 had aspartame industry funding and 92 were independently funded. Of the industry funded studies, 74/74 (100%) attested to aspartame’s safety. Of the independently funded studies, 84/92 (92%) demonstrated some type of adverse reaction.
• In 1987 Dr. Jacqueline Verrett, a toxicologist, testified before a U.S. Senate hearing and stated: “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 three studies were also present in all of the other studies submitted by Searle”.
• Dr. John Olney, Washington School of Medicine wrote a letter on December 8, 1987 stating: “Being a neuropathologist, I know that spontaneous brain tumors in laboratory rats are extremely rare. The archival literature documents an incidence not exceeding 0.6%. Since the above incidence in NutraSweet-fed rats is 3.75%, this suggests that NutraSweet may cause brain tumors and certainly suggests the need for additional in-depth research to rule out that possibility.”
• More recently a study published in September 2006 in the Annals of the New York Academy of Sciences concluded, “The results of this mega-experiment indicate that aspartame, in the tested experimental conditions, is a multi-potential carcinogenic agent.” Belpoggi F, Soffritti M, et al. Ann N Y Acad Sci. 2006 Sep; 107:559-77.

What to Tell Our Patients

• As clinicians, it is our responsibility to absorb information about health-related topics and to then make a determination as to how these facts will potentially impact our patients’ health. In the case of sucralose and aspartame we are charged with determining whether the outlined risks out way the benefits of using non-caloric sweeteners. The following points are simply a summary of my own personal thoughts.
• It is important to recognize that the doses used in experiments showing carcinogenesis, immune toxicity, or other health issues are much higher than would be consumed by our patients. Thus, I think that it is somewhat sensational to tell patients that they may increase their risk for cancer by consuming sucralose. I do not have the same confidence when it comes to aspartame, though. I also think that we have to recognize that some of our patients consume large amounts of these sweeteners through soft drinks and sugar-free foods. Additionally, it is impossible for us to determine which patient may be the “yellow canary in the mine” who may have a chemistry that expresses sensitivity to these substances.
• Thus, I tell my patients that there are legitimate questions about the safety of these sweeteners and that they should either stop using these products or limit their use. If a patient presents with headaches or has a past history of cancer I always tell them to discontinue the use of sucralose and aspartame.
• One group of patients who tend to be bigger users of these sweeteners are our diabetic patients. One position is that it is better for them to eat these sweeteners than to consume sugar. I strongly agree with this position when we are talking about soft drinks or foods containing high fructose corn syrup. Other options to suggest for our diabetic patients who have concerns over sucralose or aspartame are the sugar alcohol Xylitol, the herb Stevia, or pure crystalline Fructose. These can all be purchased at the local health food store. Have them test their blood sugars to make sure they can tolerate these sweeteners.
• Please feel free to direct your patients to www.ZimmerNutrition.com where they can read the patient friendly articles about these sweeteners.
• You can contact Dr. Zimmer with any questions, requests, or responses via email or at 317-813-1998 / toll free 1-888-813-1998