 I want you to imagine it's 1878, and you're a young, 28-year-old scientist named Konstantin Fahlberg, working at Johns Hopkins on coal tar extracts. You head for home to have dinner, and you spot a bit of something on the back of your fingers, so being an evolved ape, you lick it or otherwise put your hand in your mouth. There's an intensely sweet flavor, and you think, that's odd. We've just discovered saccharin, or an hydro-orthosulfamine benzoic acid, a substance over 200 times sweeter than cane sugar. Congratulations, it will revolutionize the sweetener industry by starting a new class of substances that are sweet, without the same calories as sugars. It will also kick off a search for other, similar substances that continues today. We'll come back to saccharin in a minute. Slash forward to 1937 at the University of Illinois. Graduate student Michael Sveta puts down his cigarette because, yes, he was smoking in the research lab, a common practice until the 1970s. He was working on anti-pyretics or anti-fever medications, but what ended up on his cigarette was a substance called sodium cyclomate, brand name, sugar twin. Another lab, another day, 1965, James Schlotter, working for a company looking for stomach ulcer medication. He was leafing through some lab papers, licked his finger, and the result was aspartame, brand name, neutrosweet. On to 1976, where a young Indian-born scientist, Shashakan Fodness, was evaluating new chemicals for use in research products. His boss asked him to test a particular chlorinated form of sucrose. He misunderstood and instead tasted what would become sucralose, brand name Splenda. Anyone else noticing a theme? I suspect the next big sweetener is waiting to be discovered on the back of someone's lab book. I suggest any of you out there that work in labs begin tasting every spill and stain on the bench. Let's jump back to saccharin. Initially it was recognized that it could benefit diabetics, and its low cost made it competitive with cane sugar, although many dislike the bitter aftertaste. U.S. President Teddy Roosevelt was quite a fan and user, and when the predecessor of the FDA proposed regulation on the use of saccharin as a cheap substitute for sugar, Teddy stepped in and formed his own scientific board to review the safety of saccharin. The board returned a positive bill of health, and saccharin remained in use thanks to presidential intercession. Saccharin became very popular following sugar rationing during World War II, and post-war America continued to use saccharin as both a low-cost and low-calorie option. Everything was great until the 1970s, when tests of the sweetener showed evidence of increased risk of bladder cancer in rats. There were immediate calls to ban the substance, but since it was the only diet sweetener on the market, it was left available, but with a warning label. And so the world decided that saccharin was a carcinogen. The labels made that very clear, and our memories are long on such things. Saccharin causes cancer. You knew that, right? In late 2000, those labels were removed. They were removed because saccharin doesn't cause cancer in humans, like it doesn't rats. Rats have some distinctive urinary characteristics that make them susceptible to saccharin's effects. They excrete protein complexes and calcium phosphate in their urine. The saccharin was being excreted, but at high pH it was forming precipitants, and this irritated the bladder lining, which resulted in a slight increase in bladder cancer. If you have a pet rat, do not allow them to drink saccharin. What about humans, though? No linkage to human cancers has ever been well demonstrated for saccharin. When the unique properties of rat urine are taken into account, it appears to be harmless in them as well. Most importantly for a possible carcinogen, saccharin doesn't interact with DNA. It's not a mutagen. The mechanism by which most artificial substances promote cancer. Admittedly, I hate the taste of saccharin, as do a lot of people. It has that terrible bitter aftertaste, and the flavor is just a little too fake tasting. But even though it's made from coal tar, it's about as safe as the sugar that's extracted from giant piles of cane grass. Switch focus to a more recent addition to the low-calorie sweetener market in the US, Stevia, or Stevia, if you prefer. Stevia is a natural product extracted from a family of shrubs and herbs. The key ingredient, a class of compounds called Steviolglycosides, or Steviocides, are hundreds of times sweeter than sucrose, yet contribute very few calories, and can actually be anti-inflammatory, and have a positive effect on regulating blood sugar. I want very much to love this sweetener, but there's a catch. Like saccharin, some or all Steviolglycosides are known to interact with DNA. Not much, mind you, and Stevia has been repeatedly cleared for carcinogenic activity, but it possesses the mutagenic potential that saccharin does not. I'm not saying it's bad, I'm saying that escalating doses of it will have escalating risks, where saccharin has a relatively flat risk. I want to kick off this video with a short discussion of the appeal to nature fallacy. You couldn't wish for a better example of it. Saccharin, which is made from oily coal residue, is the epitome of artificial and chemical. Stevia, which is a fairly crude extract of a leaf that has been used safely by people in South America and Japan for decades, is the epitome of natural products. And yet their origins in the lab or the forest make no difference in determining their safety. Ultimately, we may conclude that Stevia is a much safer product than saccharin, or that they're both safe. But it's not where they come from that determines this. Carcinogens, mutagens, and toxins are found everywhere in nature. Perfectly safe substances can be made from petroleum, coal tar, or industrial waste. It's wrong to assume the other way as well. Not every sweet tasting stain on a lab notebook is going to turn out to be a boon for mankind. But until we empirically test something for safety, there is no way to generalize based entirely on where we found it. There is an element of vitalism in this argument, a belief in the immaterial essence of something. An artificial substance will carry with it the essence of something from the harsh lights and acrid smells of the lab, where a natural substance carries only the warm sunshine and soft earth. A simple reality check on substances like tobacco, mycotoxins, and poison dart frogs will dispel this. There's another application of the appeal to nature fallacy. And that's the argument from evolution fallacy. It's tempting to say that because we evolved to eat nuts and roots, that this diet is optimal for our biology. It sometimes happens that this is true, that natural selection is weeded out undesirable traits or behaviors or eliminated toxins, or that our physiology adapted to compensate for some external force. On the other hand, natural selection is a very poor innovator. It's just as happy with a good enough solution to a problem as to the optimal solution. It's a hallmark of evolution that it never invents. It only adapts existing structures to new tasks. So it's not a reasonable argument that natural selection validates a diet or behavior as being optimal. With this perspective in mind, let's examine just a few of the major low-calorie sweeteners. Unfortunately, there are so many non-chloric sweeteners that I've had to narrow the field. I've selected aspartame, sucralose, stevia, acesulfane potassium, and some common sugar alcohols as examples. We'll have to keep the details to a minimum to keep this short. Citations in the underbar. Before we start, I want to discuss the generalized benefits of low-calorie sweeteners. One, it seems a bit redundant, but they're low-calorie. Unlike HFCS or sucrose, they don't contribute to an excess of sugar calories, which presumably means that consuming the same portion contributes less to caloric excess, which can contribute to obesity. Two, they have a low glycemic index. With the notable exception of sugar alcohols, which we will get to, low-calorie sweeteners don't cause blood sugar spikes, which is important for people with blood sugar dysregulation. Three, here's a big one. They don't contribute to bacterial erosion of a tooth enamel, so dental health is improved. I could add lower cost here, but I personally don't think that's the case to the consumer anymore. Intense sweeteners have become associated with more expensive diet forms of popular products. What about the possible generic risks to any sweetener? One, overcompensation. This is a big one, and very controversial right now in the research community. People may, and I emphasize may, give themselves permission to eat foods bad for them. If they also consume a product perceived as diet or low-calorie, think of someone on a weight reduction diet who orders a diet coke with their McDonald's triple cheeseburger and large fries. They might buy the diet coke and justify their rest because they're cutting back on calories on the soda. The research to date has found very little evidence of this. Most studies support the use of low-calorie sweeteners for weight loss, but there are a few, especially on non-human models, that show a paradoxical weight gain, and the cause is not entirely clear. Two, addiction to sweetness. Low-calorie sweeteners reinforce our brain's demand for sweeter flavors. This might mean that we prefer foods with harsher additive-derived flavors, rather than adjusting to the softer sweetness of unmodified foods. I'm an advocate of a diet rich in vegetables and fruit, but it would seem harder to get kids to eat strawberries for dessert if they get used to super-sweetened candy or sugar-sweetened cakes and cookies. Again, there is very little evidence to support this intuitive conclusion. When people are presented with a choice of foods after drinking either sucrose-sweetened or artificially-sweetened drinks, they still made the same choices, either good or bad. Three, uncoupling the expectation of satiety and the blood sugar spike. Recent research has focused on whether people eat more food after drinking a sugary drink or an artificially-sweetened drink. Our bodies anticipate meals and begin preparing well before the first calorie of food enters the mouth. If we anticipate a blood sugar spike but none happens, what effect will that have? So far, the majority of studies point to no difference between sugar and, say, aspartame containing beverages on hunger, food selection, and food intake, but it's worth further research. The rest I'll say for discussion on the particular sweeteners, one, aspartame. I did briefly discuss aspartame in my video on MSG, because they're related compounds. Aspartame is aspartic acid and phenylalanine joined with a methanol backbone. Both of these subunits, called amino acids, are found throughout the body as part of proteins. The methanol is processed very rapidly in your liver and detoxified. Now if you are the type who forwards emails about aspartame being linked to MS or lupus, there's very little I could do to convince you. The same for people who think Jo Merkola is an authority on health research or who believe that the government is controlling your brainwaves through secret military broadcasts. For those of you who care about evidence and understand how science works, aspartame is one of the most studied sweeteners. We're pretty certain that for healthy, normal people, there are no adverse effects below a certain threshold that your body can handle. That amount is around 50 milligrams per kilogram of body weight, so a 160-pound person could handle 3,600 milligrams or 3.6 grams. A packet of Equal contains about 33 milligrams, so about 110 of those in a day would exceed your daily allowance. Diacoke on the other hand contains about 131 milligrams per can, so more than 27 of those per day would be a real problem. Of course you'll need to do some label hunting to find all the diet products that contain aspartame. Certain rare individuals with a condition called phenylkinonuria should avoid anything with aspartame in it as they're unable to break down excess phenylalanine and it builds up to toxic levels. Is aspartame linked to chronic disease? Animals have been subjected to amounts a hundred times the safe level in humans for periods of months with no increase in cancer or chronic disease. The weight of the published evidence is that consuming a safe level of aspartame does not increase your risk for any disease. I anticipate someone is going to cite the claim that in a critical review of papers on safety, those studies that were funded by industry were 100% in support, while papers by independent agencies identified problems in 92% of cases. I spent a little time reviewing the two lists and I identified the cause of the disparity. The industry supported papers were tests of safety in dietary consumption. The independent papers were in one of three categories. 1. Known activists opposed to oxytotoxins 2. Using aspartame to induce an animal disease model not observed in humans 3. Documenting cases of sensitivity to aspartame with symptoms like dizziness, headaches or mood disorders not revealing serious chronic disease. I have no doubt that funding source is biased research. But in this case the very worst effect found was an increased potential for seizures in certain animal models at extremely high doses. The same effect has not been observed in humans at safe doses. 2. Sucralose Sucralose is a chlorinated sugar compound. The marketing slogan is made from sugar so it tastes like sugar, which is attempting to harness the argument from nature. Three of the hydroxyl groups in sucrose have been replaced by chlorine. As a result it is largely unmetabolized and therefore low calorie. It also makes it about 600 times sweeter than sucrose, so very small amounts are needed. So little is needed that it is almost always sold with a filler material, usually a blend that includes maltodextrin, which is itself a sugar. Critics of sucralose will point out that organochlorides or chlorocarbons are not common in nature and include a number of particularly nasty toxins. However, sucralose of all the sweeteners seems to have the strongest evidence in favor of safety. Rat studies have been conducted at escalated doses over a two-year time course from fetus to late adult and the rats had no increase in disease or cancer and a general reduction in weight gain, although this was found later to be complicated by the fact that the high sucralose was less palatable to the rats. The rats that were fed 3% sucralose did have elevated risk of certain renal conditions at older ages, but this was attributable to the fact that so much sweetener was being processed by the kidney that it sometimes mineralized there, much like the issues saccharine had in rats. At relevant doses there was no risk escalation. I still think we need to keep an eye on any substance that is excreted in urine, but there's no good evidence to be especially concerned about this in splendid type products. One initial study in the 90s found some shrinking of the thymus in a rat population, but this result couldn't be repeated by other groups and it's likely it was a statistical fluke. An interesting source I came across is the CSPI or Center for Science in the Public Interest, a research watchdog group with no industry ties or support. They tend to be hypersensitive to risks and lead towards anti-corporate perspectives, but while they are critical of lack of data on aspartame and some other sweeteners, they rate sucralose as safe the only sweetener to get this rating. I'll be honest, I found this pretty compelling. They scrutinize both the research and regulatory data before making a call and it says a lot that they put sucralose in the category of safe to consume. If you must drink sweetened sodas, I think looking for splenda sweetened wouldn't be a terrible idea. 3. Stevia. I think stevia sides will ultimately be a safe and useful sweetener. They have a long tradition of apparently safe use in Japan and South America and they have some really great side effects. They are anti-inflammatory as I mentioned and they seem to help regulate blood sugar properly. There is some weak evidence to suggest that the products in stevia may be useful in treating chronic diseases. Stevia sides are almost completely untouched by our digestive system, but the gut bacteria often process it from stevia side to steviaal, which usually exits the body in feces, but steviaal can be a nasty substance at extremely high doses. In pregnant hamsters it levels 100 times the level humans might consume. It causes severe toxicity in both the mom and fetus. It also causes defects in sperm production in male hamsters and we know it interacts with DNA, which is usually an indication that it can lead to both cancer and birth defects. Very recently studies have also raised some concern about effects of excretion in the kidney, something we also saw in aspartame and sucralose. Right now you can't sell stevia extracts as a sweetener. The FDA looks the other way if they're labeled as dietary supplements, which is a loophole I've never liked. However, a purified component of stevia called REB-A has been approved as a commercial sweetener. It's manufactured by Cargill and Mericent and marketed by Coca-Cola as Truvia or Purvia. You'll see Truvia sweeten products on the shelf very soon if you haven't already. The CSPI and some toxicologists from UCLA urge the FDA not to approve stevia or REB-A until further studies can be completed. And I have to say I agree, but in 2008 they granted REB-A generally recognized as safe or GRAS status. On the other hand, applications in Canada and Europe were rejected. 4. Acesulfame Potassium I'm going to call this one ACK for short. It's about 200 times sweeter than sugar and like sucralose it largely passes through the body, unmetabolized. However, unlike sucralose there is some evidence that it looks just enough like a carbohydrate to stimulate a dose-dependent insulin response, which makes me a bit concerned. What bothers me most about ACK is the lack of data. It's a bit odd to find over a thousand papers on aspartame in PubMed, but only a hundred on ACK. I'm not the only person to notice this. There were really only three large-scale tests of toxicity done, and none of them were very powerful tests. There were even some troubling findings around cancer risk. My only explanation is that this work was done in the 1970s in the U.S. and there was a growing need for some sweetener to replace saccharine. The CSPI and I agree here as well. I would probably avoid ACK when possible or keep my consumption to a very low level. I'd really like to see more testing done here. A modern revisit to ACK's safety is probably long overdue. The reason why this deficiency really bothers me is the new trend for blending sweeteners. Manufacturers are looking to find a combination of intense sweeteners that have certain properties like aftertaste and bulk, hiding bitter flavor components or shelf life stability. If an unsafe sweetener is blended with a safe one, it will be very hard for those with concerns to control our intake. Five, sugar alcohols. I want to end on sugar alcohols, which are not necessarily low calorie nor low GI. In fact, your body can utilize some sugar alcohols quite effectively after some processing. There's a lot of variation in this category. Only erythritol and arabitol would qualify as intense sweeteners or low calorie. Sorbitol and maltitol frequently used by low carb dieters are actually higher calorie than the same sweetness of sucrose. One of the more common places to find sugar alcohols are in candies and sugarless gum. Sugar alcohols are almost certainly non-carcinogens and non-mutagens, but if you've ever eaten too much of them, you know what the primary problem is. Gastrointestinal distress. Somewhere between 10 grams and 40 grams you cross a threshold where you have gas, bloating, diarrhea, and this can even be severe in sensitive people. In my last video on sweeteners, I covered sucrose and high fructose corn syrup. I concluded that both were equally bad. They represent the collision of our desire for sweetness with the continuous availability not previously known by our ancestors, and they put us at risk for chronic disease and obesity. With the high intensity sweeteners, we still satisfy that craving for sweetness, but with fewer calories. It's a solution to a problem that's sorely needed. If I had to choose a sweetener on the basis of safety, I would probably prefer sucralose, the ones I have concern about are ACK and Stevia. The best solution, I suspect, isn't the product of a laboratory. It's a modification of behavior. We need to adjust our taste palates to the natural flavors of healthy foods. Given the choice between sucrose, high fructose corn syrup, and almost any of the sweeteners on this list, I'd say whatever you can do to avoid excess of sugar calories is probably best. Thanks for watching.