A T-Nation Consumer Report
All too often I'll hear various statements about certain artificial sweeteners being harmful. "Toxic" seems to be a word that the general public likes to throw around. In the following article, I'd like to address some of the completely false statements I've seen being made about one sweetener in particular: sucralose.
Before I do that, however, I want to give a quick toxicology lesson.
Is This Toxic?
When people say that a given compound might be "toxic" without any further explanation, it's really an incorrect use of the word in a strictly toxicological sense. The reason? Well, just about anything can be toxic at a given dose.
NaCl or table salt can be toxic, at a given dose. Oxygen (yep, O2, the stuff you inhale) can be toxic at a given dose, too. Another life sustaining substance, water, can be toxic as well... at a given dose. As the toxicology professor used to say, the dose makes the poison.
Furthermore, "toxicity," or a toxicological response, is something that needs to be described for a given compound. For example, a response could be things like diarrhea and nausea or slightly increased heart rate, or it could be something much more harmful, like arrhythmia or a coma. This is why toxicologists invest so much in the principle of developing a dose-response curve for a given chemical. It allows them not only to understand at what dose a chemical will start to have a given effect, but what those measurable effects may be.
Now, the reason I mention this is simply because while valuable for toxicologists, employing such methods creates areas for certain authors to create hysteria, false concerns, and even downright false statements about certain chemicals. What the general public doesn't understand is that when these scientists are trying to establish a dose-response curve, they're going to keep increasing the dose more and more until a response is observed in the given tissue/organ or entire organism, whatever the case may be.
However, this unfortunately makes for an easy assault by those who wish to create false concern as they can point and say, "You see what happened when they gave it to this animal!" Obviously, this couldn't be more misleading.
For example, administering oxygen or water at one end of the dose-response curve, you'd see no harmful effects. Going further along the line however, you'd start to see that you have deleterious effects (nausea, dizziness, vomiting) continuing further and further along, typically accruing more and more severe side effects until a peak or maximum response is seen (death in these cases).
So, using this type of "logic", oxygen and water are toxic and can kill you!
Sucralose: The Whole Truth
Now, having said all of that, I'd like to directly address some of the completely false statements I've seen made about sucralose and talk about some of the studies that have been conducted on it. Please keep what I've said above in mind throughout the article.
False Statement #1: Sucralose is structurally similar to DDT and thus is fat-soluble and gets stored in your body fat where it'll cause deleterious effects.
In actuality, sucralose is in no way similar to the pesticide DDT. Sucralose isn't lipophilic like DDT, but freely soluble in water, as one would expect.
This is something that simply can't be disputed and is a matter of very basic principles. Even if you didn't know the physiochemical properties of each compound, any person who's ever taken organic chemistry should be able to look at the large number of hydroxyl groups and oxygen atoms on the sucralose molecule and realize it's ideal for a great deal of hydrogen bonding, while DDT obviously lacks such a thing.
However, you won't need a single course in chemistry to be able to see that sucrose (table sugar) is much more similar to sucralose than DDT, as you'd obviously and logically expect. DDT and sucralose are in no way chemically or pharmacologically similar.
Sucrose (Table Sugar) (1)
Statement #2:Sucralose is absorbed, even though the manufacturers claim it's not, and metabolized after ingestion. Then some of it finds its way to the liver and kidneys.
In reality, I've never seen where the manufacturers of sucralose have claimed that it isn't absorbed. Poorly absorbed yes, but I've never seen in one paper in the literature where the authors claim that it isn't absorbed. Rather, the only claim that I've seen from the manufacturer was that sucralose isn't metabolized in the sense of being used as an energy source.
The statement that sucralose is distributed to the liver and kidneys is yet another to make the average person think that this is some unique event and that the "toxic" sucralose will cause renal and hepatic damage. The truth is that this is a basic route of metabolism that most certainly isn't unique to sucralose.
And what about sucralose being metabolized? Again, the word "metabolized" is being misused, deliberately or not. Sucralose is metabolized in the sense that the liver conjugates it so that the kidneys can excrete it (again a basic pharmacological principle). Again, it's not hydrolyzed or metabolized for energy, as this hasn't been demonstrated in any of the species studied, including humans. (2-14)
Statement #3: Sucralose caused caecal enlargement and pelvic mineralization in rats.
This statement is true, however, going back to what I discussed earlier, this is a result of feeding the rats extremely large amounts. (And by the way, such an effect wasn't seen in mice, dogs, or non-human primates.)
In fact, this same exact thing occurs when rats are fed large amounts of other poorly absorbed, osmotic compounds such as lactose, xylitol, sorbitol, polydextrose, and magnesium sulfate. This makes it obvious that this is a side effect unique to rats, which occurred as a result of the sucralose being poorly absorbed and osmotically active. The World Health Organization has even come to similar conclusions in terms of poorly absorbed and osmotic compounds causing caecal enlargement. (The caecum is part of the large bowel, in case you didn't know.)
Last, but certainly not least, men were administered 1,000 mg/day of sucralose for 12 weeks and found no gastrointestinal side effects. (2-14)
Statement #4: They might have the pharmacokinetic data for animals and humans, but there's no way to predict how much humans will consume in the real world, nor if that amount is safe.
I'd like to address this by explaining how the acceptable daily intake (ADI) and estimated daily intake (EDI) are determined for a compound like sucralose.
First, what they did was choose the highest dosage in animals where no adverse effects were observed. In this case, the rodents were fed ~1,500 mg per kg of bodyweight per day for 104 weeks with absolutely no adverse effects whatsoever. This was therefore determined to be the highest no-adverse-effect level (HNEL).
From the HNEL, the ADI is determined. The ADI is considered to be the amount of a food additive which could be consumed during a human's entire life and would be considered safe by a large margin. They do so by dividing the HNEL by a large safety factor of 100 fold (though in some cases it may be more or less). This therefore gives an ADI of 15 mg/kg of bodyweight per day. Ideally, the ADI should also exceed the amount that's considered the EDI.
After this, they determined the EDI by having an independent research group survey 2,000 households by asking each to keep a detailed diary for two weeks, keeping track of all food and beverages consumed. From this the researchers then assumed that sucralose would replace all sweeteners, including sugar, in all of the foods and beverages for which it would be approved for use in.
Their analysis revealed that even in the highly unlikely event sucralose replaced all such sweeteners, and again sugar as well, the EDI was 1.1 mg per kg per day, for people of all ages. They then also calculated an EDI for those who may consume sucralose in a larger amount than most others throughout their lives (i.e., those in the 90th percentile for consumption), and found an EDI of 2.3 mg/kg/day. As you can see, there is level upon level of safety factors.
As a side note, daily dosages of 4.8 to 8.0 mg/kg for human males and 6.4 to 10.1 mg/kg for females were given over a 13-week period and found to cause no adverse effects. As an interesting note, in order for a 160-pound human to reach an amount equivalent to the HNEL, he'd have to ingest 1,500 twelve-ounce sodas every single day. (2-14)
Oh, and before someone claims that this is some flawed program, the ADI was initiated by the Joint FAO (Food and Agriculture Organization)/WHO (World Health Organization) Expert Committee On Food Additives. While I think most people should recognize these prestigious committees, for those who may not, I'm including a direct quote from a paper that explains how the members are selected in the references.* (15)
Statement #5: Sucralose breaks down into compounds which haven't been studied.
While this hasn't been shown in vivo in any species, sucralose can hydrolyze, very slowly, into two compounds, provided that the conditions are right. For example, after one year at 25°C and a pH of 3, hydrolysis of less than 1% of the sucralose occurs. At a pH of 4 and 6 however, no loss is detected.
In essence, sucralose is extremely stable and the idea that you'd encounter little, if any, of the hydrolyzed products is pretty unlikely. Nonetheless (and contrary to what some say) these compounds have been studied. Both were studied for any carcinogenic, genotoxic, neurotoxic, and reproductive toxicity, and nothing of any toxicological significance to humans was found. (2-14)
Statement #6: Sucralose has chlorine atoms in it so it's basically like you're eating chlorine!
As ridiculous as a statement like this is, I believe that this was likely brought up during the FDA review process, where anyone, regardless of their background, could've submitted a question or comment and had it given complete consideration. Since any consumer interest group and even competitors could have submitted questions and comments during the review, I'd assume this was where it stemmed from.
The statement is completely false. Dechlorination doesn't occur in vivo in any of the species studied, nor would it realistically be expected. People also need to understand that diatomic chlorine gas (Cl2) is not to be confused with a single chlorine atom, as it's paired with another, different atom. Just as an example, you do in fact have chlorine in the form of KCl and NaCl in your body right now.
Unfortunately, some people will take data from the effects known from Cl2 exposure and try to pass that off as "evidence" of what will happen if you consume sucralose, which is just plain nonsense. (2-14)
Statement #7: There have hardly been any studies on sucralose.
There have been 113 studies conducted on sucralose and its hydrolyzed metabolites for over 20 years. (2-14)
A Note On Stevia
I've often seen comments from people claiming that stevia is the best thing since sliced bread and that the FDA has a hidden agenda (I have no clue what that is) and thus won't approve it as a sweetener. Well, there are actually a few very good reasons that I doubt you'll ever see stevia approved as a sweetener in the U.S., at least not without some modifications or warnings to certain portions of the population which I'll discuss later.
First, I'd like to look at some of the safety data on stevia. Rats were given 838.9 mg of stevia per kg of body weight each day for 104 weeks and no adverse effects were noted, leading to a suggested ADI of 7.938 mg/kg for humans. Hmm, I could've sworn that I'd seen something similar to this, perhaps given in greater amounts for another compound. In fact, I think this other compound had nearly doublethe ADI. Hmm.
Moving on from sarcasm, stevioside hasn't shown to be teratogenic in rats, mice, hamsters, or guinea pigs; however, stevioside and steviol have shown some possible mutagenic effects in some assays. To be fair, other studies were negative for mutagenic effects. (16-18)
I could also mention that stevia has been shown to cause renal toxicity in rats, but instead of conveniently leaving out details of toxicological significance like some "experts," I'll also mention that the route of administration (IV and Subq inj.) and amounts used make the applicability to human consumption highly questionable. (19-21)
I could also cite a study which found that stevia reduced fertility in rats. Again, however, I won't neglect to mention that a later study refuted these findings. (22-23)
Last, I could also point out that stevioside displaced DHT from androgen receptors, perhaps indicating a pro or anti-androgenic effect. It also demonstrated an anti-fertility effect in male rats, including a decrease in Testosterone levels. Again though, I'd be neglecting to mention that the concentrations used in this in vitro assay, as well as the dose in the rat bioassay, were well beyond those which would likely be seen in humans ingesting the substance. Furthermore, other studies haven't found such adverse effects. (24-27)
I hope my first point of this article, where I discussed what a toxicologist is always trying to accomplish when studying new compounds and how it's easy for someone to point out some aspects yet leave others out, is coming across.
As for my mentioning that stevia will have a more difficult time gaining status as a sweetener, the reason I say this is simple. Studies in humans have noted that stevia can cause a decrease in heart rate and a decrease in blood pressure (having a hypotensive effect). While those pharmacological effects can be potentially beneficial for those that may be suffering from certain conditions, when you broaden the use to the entire U.S. population, it's not such a great thing.
People taking beta-adrenergic blockers or calcium antagonists, not to mention a number of other drugs, could have severe side effects. Ideally, a sweetener should be just that, and not impart any other effects. Similarly, while the effects upon blood glucose are positive, it also requires caution for those that are diabetic and using certain medications. Additionally, some may feel there are some issues which remain to be resolved. (28-29)
In summary, there just isn't any data supportive of the idea that sucralose is harmful when used by humans. I'm sure the next thing I'll hear is that famous statement, "There just aren't any long-term studies in humans!" Well, unfortunately, the same can be said for just about anything.
The "long-term" studies for just about everything you ingest (if they exist to begin with) are typically no longer than a matter of a few years. Sure, if a population is followed long enough and thoroughly enough, epidemiological data can be gathered, but the power of such studies isn't always sufficient and may not be able to detect small risks.
We must also keep in mind that epidemiological data's purpose isn't to "prove" that a compound is completely harmless. In short, there's no absolute guarantee that everything you ingest each day is completely safe in the long run.
The possibilities of carcinogenic and other negative effects are evaluated just as with sucralose in animal models and in vitro assays. Most important with those methods is that pharmacokinetic data be gathered and made certain that differences in bioavailability are accounted for, as well as qualitative metabolism. If there are no discrepancies there and the level of exposure in humans is assessed and comparable to the animal models, there's very little reason for doubt of safety. Though, there are of course exceptions.
I'm also tired of certain conspiracy theory personalities complaining that animal data doesn't mean anything, yet they use animal data (dubiously) to try and provide evidence when it comes to a lack of safety. Well, which is it?
Also, I'd like to make a note about anecdotal reports. While I'm not discounting such reports by those that think they may have had a negative reaction to sucralose, it's important to note that having a hypersensitivity reaction can happen with just about any substance, even those that are extremely common.
In fact, in one of the studies with sucralose, the subjects were either given sucralose or fructose. In the group taking fructose, two had to withdraw as one developed a skin reaction, which went away after discontinuing use and reappeared when fructose was ingested once again. The other developed a sore throat, which discontinued once fructose ingestion ceased. No such effects were seen in the group taking sucralose. (2-14)
That aside, there's also the strong possibility of placebo effects and/or coincidental reactions. I don't think most people understand how many adverse reactions are seen in placebo groups during clinical trials with various drugs. I'm not talking about those that are easily explained either; I'm talking about rash, vomiting, lesions, headaches, insomnia, psychiatric side effects, you name it.
In the end, I'm not attempting to convince those that have already made up their minds one way or the other. Rather, I'm addressing those that are sitting on the fence. For those that are against consuming sucralose for whatever reason, I'm not saying you're stupid or outrageously paranoid. You're absolutely right to say that there's no way to say with complete and absolute certainty that sucralose is 100% completely safe across all subpopulations and across the board in terms of length of exposure and so forth.
My point, however, is that we can't really say that for a number of substances that are ingested each day. Further, I'm saying that the current available data indicates that sucralose is a safe compound.
My main reason for writing this has really nothing to do with those that choose not to consume sucralose or other artificial sweeteners; rather, I became almost ill after seeing the completely false statements perpetuated over and over on the Internet and wanted to present the data as it was.
Oh and just as with my article on fluoride, I'm open to discussions, provided that they have some data behind them. But again, I'm not talking about links to websites where the references are links to other websites. And I'm not talking about statements from people or their book.
Disagree with me? Then let's discuss it. But you better come armed with real data, bubba.
1) ChemIDplus. National Library of Medicine (Specialized Information Services)
2.-14. Food Chem Toxicol. 2000;38 Suppl 2:S1-129
2) Lu FC. "Acceptable daily intake: inception, evolution, and application." Regul Toxicol Pharmacol. 1988 Mar;8(1):45-60.
3) Xili L, et al. "Chronic oral toxicity and carcinogenicity study of stevioside in rats." Food Chem Toxicol. 1992 Nov;30(11):957-65.
4) Suttajit M, et al. "Mutagenicity and human chromosomal effect of stevioside, a sweetener from Stevia rebaudiana Bertoni." Environ Health Perspect. 1993 Oct;101 Suppl 3:53-6.
5) Pezzuto JM, et al. "Metabolically activated steviol, the aglycone of stevioside, is mutagenic." Proc Natl Acad Sci U S A. 1985 Apr;82(8):2478-82.
6) Mauri P, et al. "Analysis of Stevia glycosides by capillary electrophoresis." Electrophoresis. 1996 Feb;17(2):367-71.
7) Melis MS, Sainati AR. "Participation of prostaglandins in the effect of stevioside on rat renal function and arterial pressure." Braz J Med Biol Res. 1991;24(12):1269-76.
8) Toskulkao C, et al. "The low calorie natural sweetener stevioside: nephrotoxicity and its relationship to urinary enzyme excretion in the rat." Phytother Res 1994 (8):281-286.
9) Mazzei Planas G, Kuc J. "Contraceptive properties of Stevia rebaudiana." Science. 1968 Nov 29;162(857):1007.
10) Shiotsu S. "Fertility study of Stevia decoction in rats." Tech. J. Food Chem. Chemicals 1996 4:108 – 113.
11) Uehara OA, et al. "Stevioside-androgen interactions." 7th Symposium Braz. Med. Plants, Manaus 1982 1:74.
12) Melis MS. "Effects of chronic administration of Stevia rebaudiana on fertility in rats." J Ethnopharmacol. 1999 Nov 1;67(2):157-61.
13) Yamada A, et al. "Chronic toxicity of dietary Stevia Extracts." J. Food Hyg. Soc. Jpn 1985 26:169 – 183.
14) Oliveira-Filho RM, et al. "Chronic administration of aqueous extract of Stevia rebaudiana (Bert.) Bertoni in rats: endocrine effects." Gen Pharmacol. 1989;20(2):187-91.
15) Melis MS. "A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats." Braz J Med Biol Res. 1996 May;29(5):669-75.
16) Kinghorn AD, Soejarto DD. "Current status of stevioside as a sweetening agent for human use." Econ Med Plant Res 1985 1:1-52.
*Members are selected from a panel of internationally known experts. Panel members are chosen according to their special expertise, international standing, and agreement of their respective governments. In attending the WHO Expert Committees, they "act as international experts serving the Organization exclusively; in that capacity, they may not request or receive instructions from any government or authority external to the Organization," and "they shall enjoy the privileges and immunities . . . set forth in the Convention on the Privileges and Immunities of the Specialized Agencies," as stated in the WHO Regulations for Expert Advisory Panels and Committees (Basic Documents of WHO). Furthermore, to ensure that individual members retain their scientific judgment and conviction, they have the privileges of issuing a "minority report." Since the meetings are private, uninvited persons are not admitted. This practice allows the members to express their scientific judgment freely at the meetings. Furthermore, the Expert Committees are ad hoc in nature. In other words, at the end of the meeting, the Committee is disbanded, thus freeing the Members of any responsibility for the decisions and recommendations incorporated in the Report and any other documents prepared during the meeting.