Critical Examiner

Artificial sweeteners are sugar substitutes that provide no nutritional value and are made by chemical processes, rather than naturally occurring in the environment.  As such, there’s always a lot of negative attention directed toward artificial sweeteners and indeed, anything labeled as “artificial.”  I’ve decided to do a series of articles on artificial sweeteners to find out what claims are true and what isn’t, instead of doing one article with a bullet point list.  There’s just too much information to condense everything into one article and I like to include as much context as possible because most things are not black and white issues, and this topic is no exception.  So the first article in this series will concentrate on what science currently has to say about the most widely used artificial sweetener on the market: sucralose.

Sucralose (Splenda)

Surcalose, best known as the key ingredient in Splenda, is a non-nutritive sweetener 600 times sweeter than sugar by weight.  The molecule itself is produced by a series of chemical reactions, starting with sugar as a base, then, stripping away 3 hydroxyl groups from the original sugar molecule and replacing them with chlorine atoms.  The added chlorine atoms make sucralose sweeter than sugar while also preventing it from being metabolized by the body.  This means that sucralose is not used as an energy source by the body and is simply eliminated as a waste product.

Sucralose is made from table sugar by displacing 3 -OH groups (green) with chlorine (red).

Numerous studies have been conducted to observe what happens to sucralose after ingestion in humans.  One such study found that on average 86% is eliminated unchanged in the feces over 5 days following a single dose of 1mg/kg body wgt of sucralose, while a small amount (14%) is absorbed and eliminated in the urine.  Similar results were found when the dose was escalated to 10mg/kg.  Most of the products recovered were unmodified sucralose, indicating that it likely isn’t reacting with anything in the body, but 2% of the total recovered portion was found to be 2 different metabolites of sucralose that were identified here, and in a seperate study, as glucuronidation products of phase II detoxification in the liver.  To be clear, “detoxification” in this context does not necessarily imply that the liver is removing a “toxic” or dangerous substance.  Glucuronidation is simply a process that makes a molecule more water soluble so that it can be removed as a waste product more easily.  It may go without saying but: systemic circulation, and, indeed our entire bodies, are composed primarily of water.  As such, anything that we don’t want our bodies to absorb should dissolve in water easily (water soluble), and remain in this state as it passes through circulation.  For instance, certain hormones that are produced by the body are water insoluble (lipid/fat soluble) and must undergo phase II detoxification and glucuronidation in the liver in order to be eliminated from the body.  Most drugs are glucuronidated as well.  This is a good thing because sucralose can not be used by the body anyway and we need to get rid of it.

However, it also raises a valid question about the water soluble nature of sucralose.  From a chemistry standpoint sucralose has 5 hydroxyl groups (-OH), making it highly water soluble because the -OH portion readily interacts with water molecules.  The 3 chlorine atoms could potentially have a small destabilizing effect because chlorine itself is only slightly water soluble, and that may explain why a small percentage of sucralose is recovered as glucuronidation products.  If there is a point where sucralose becomes water insoluble in the body, then it allows for the possibility that sucralose could move into lipids and be stored in fat (more on this point shortly).

The numbers given in the above study are the averages of the entire test group.  Even though the average recovered percent of sucralose at the end of the study was 100%, the individual amounts varied per person.  This is true for most studies I’ve looked at.  It’s not uncommon to see up to 10% of ingested sucralose that is not recovered by the end of the study.  I suspect that a lot of the variation comes from the assays used to measure the amounts of sucralose recovered.  Anyone who has taken a basic chemistry lab course knows how difficult it is to recover 100% of any product whether or not the product is changed from a chemical reaction.  Further, we know that a small percentage of sucralose does get absorbed and undergoes some changes in the body.  There’s always some loss inherent with any biochemical assay and I’m guessing that’s the case with sucralose, especially since the researchers are collecting up to three different sample types from each individual (fecal, urine and blood) over the course of a week.  I think it would stand out more as an anomaly if they recovered 100% from every individual.

With that being said, if there is any cause to think that sucralose is being absorbed and stored in fat, then it needs to be examined.

I think its interesting that research funded by interests in the sucralose industry claim that sucralose does not bio-accumulate simply because the structure of the molecule makes it very water soluble by virtue of having many hydroxyl groups.  Yet in the same breath, extol the fact that sucralose can be used in both fat and water containing substances…this could not be said if the molecule did not have fat and water soluble properties (amphiphilic).  The scientific literature points to two industry funded studies, this one and this one, that use radio-labeled carbon to track the distribution of sucralose after ingestion by rats claiming that the small amount of absorbed sucralose is evenly distributed to all tissues, indicating that sucralose remains in a water soluble state and not absorbed by fat.  I do not have access to these articles, however, so I can not critically evaluate the information myself.  However, it would be interesting to see fat tissue tested specifically in rats or mice that were chronically fed sucralose and then removing sucralose from the diet for several weeks to see if anything is found to be absorbed in the fat after having sufficient time to be eliminated from the body, but as far as I know, no such experiment exists.

The FDA has set the ADI (acceptable daily intake) of sucralose to 5mg/kg body wgt/day.  They arrived at this number because studies in animals have shown that consuming 500mg/kg body wgt/day have shown no toxicity, and other studies have shown that sucralose doses of up to 200 times that amount have shown no observed effect in rats and mice.  Additionally, there’s been no evidence that sucralose is mutagenic, genotoxic or carcinogenic (it doesn’t damage DNA or cause cancer).  The FDA has to play it safe and set the daily limit to a reasonable number when determining acceptable daily limits, so by dividing 500mg/kg/day by 100, we come to the ADI of 5mg/kg/day.  The average daily intake for a consumer of sucralose is about 1-3mg/kg body wgt/day.  To put all of this into perspect, a packet of Splenda contains 11.9mg of sucralose, this means a 150lb (68kg) person can consume 28 packets of Splenda in a day and still be within the ADI set by the FDA.  A 12oz can of soda sweetened with sucralose contains 70mg of sucralose, so this person can also consume roughly 5 cans of soda per day.  To reach the no-observed-effect dose of 500mg/kg/day they would have to drink a ridiculous amount of 486 12oz sodas or 2,857 packets of Splenda.

With that said, should we be concerned about the small amount of sucralose that may be absorbed, despite evidence that suggests sucralose is harmless?  Probably not, but I think it’s a question that certainly merits further investigation, if this stuff is being stored in our fat, does it just accumulate forever?

Daphnia magna – a freshwater crustacean that may be effected by sucralose.

It seems very unlikely that sucralose is undergoing any chemical reactions within the body.  In fact, sucralose is so stable that it has been found completely unchanged in sewage, waste water, drinking water and as far reaching as the Atlantic Gulf Stream.  Sucralose is heat stable and only begins to breakdown in highly acidic conditions.  For example, 1% of sucralose is broken down under acidic conditions (pH~3) at room temperature for a year, but remains stable at anything above a pH of 3.  The half life of sucralose in ordinary water is on the order of several years, that is, it takes several years for half of the sucralose in a given sample of water to degrade.  Historic studies have not shown that sucralose presents any danger to aquatic life, however, recent evidence has suggested that sucralose alters the swimming behavior of certain crustaceans and may be exhibiting neurotoxic effects in these animals related to elevated acetylcholinesterase activity.  Turns out, its really difficult to remove sucralose using traditional methods of water treatment, but may be treatable using an electrochemical oxidizing processes that turns sucralose into harmless fructose and sugar alcohol.  The problem of sucralose persisting in water sources for long periods of time is not going away any time soon, as the use of artificial sweeteners increase.

There have been other issues that have been raised as well, this review covers them in detail.  However I find it to be highly speculative, using poorly controlled studies as evidence and drawing conclusions based on other “organochloride” molecules which are mostly irrelevant to the discussion, but they do make some good points which I have already covered.  For example the basis of many of their claims comes from one study finding that Splenda given to mice at ADI levels altered the amounts of beneficial bacteria in the gut, they make other claims as well such as Splenda altered levels of certain proteins involved in drug metabolism.  However, the study appears to have been poorly controlled, the experimental mice received varying doses of Splenda, while control mice only received water.  Splenda consists of 1% sucralose and 99% maltodextrin, a complex carbohydrate (polysaccharide), so in this case the control mice should have received equal amounts of maltodextrin, not just water, to rule out the possibility that fluctuations in bacteria levels were due to carbohydrate intake.  Additionally, the Western blots used to evaluate protein expression do not appear to control for blot to blot variation and do not seem to indicate a dose response.  Taken together, these issues invalidates the claims made in their paper, but I think the study is worth repeating.  It is unfortunate since a separate study found that sucralose can inhibit growth of bacteria in the mouth that cause gum disease, and while this would actually be a positive side effect of sucralose, it also implies that sucralose can have an effect on bacteria.  Gut bacteria are extremely important to human health, so this would be an important finding if true.

Clearly, the potential environmental impact of sucralose has been under-appreciated and probably overshadowed by the desire to prove or disprove its safety in regards to human health, but it remains an issue that needs to be closely monitored.  Overall, the evidence does not suggest sucralose is the cause of any obvious discernible negative health effects in humans.  To achieve an equivalent sweetness of a 12-ounce soda sweetened with 0.07 grams of sucralose one would have to use about 40 grams of sugar (over 99% more sugar than sucralose), an amount that already exceeds the recommended dietary guidelines by 6 grams.  I’ve already touched on how dangerously high the American carboyhydrate intake has become over the last 30 years in my article about high fructose corn syrup, and that is without a doubt contributing to or exacerbating many health problems.  There’s no solid evidence that shows that sucralose leads to weight loss and some of the information out there is poor and conflicting.  Its possible the body might be compensating for the lack of nutrition compared to the perceived sweetness of the product, but we still need some good studies in humans to evaluate this possibility and examine a potential connection between sucralose and satiety.  Still, I think substituting 40g of sugar a day with sucralose is a good trade-off.  Of course, reducing sugars and cutting artificial sweeteners entirely will always be the best option.