 You may have heard the expression, knowledge is power. Well, today we're going to give you more power to control your diet and lifestyle by giving you the facts. Welcome to the Nutrition Facts Podcast. I'm your host, Dr. Michael Greger. Today we look at the safety of fourth generation sweeteners, such as the rare sugar allulose. First there was sugar and high fructose corn syrup, the original industrial sweeteners. They were cheap, but had lots of empty calories and contributed to diseases such as obesity, type 2 diabetes, cavities, and metabolic syndrome. So then came the second generation sweeteners, the artificial sweeteners, the colored pastel packets, neutrosweet, splendor, sweeten low. Practically zero calories, but adverse effects have been described, cautions have been raised. For example, artificial sweeteners were found to induce glucose intolerance by altering the gut microbiome, thereby producing the counter-intuitive effect of inducing metabolic derangements. They also taste kind of funny. Enter the third generation sweeteners, sugar alcohol, such as sorbitol, xylitol, and erythritol. Low calorie sweeteners, however, their laxative effects can create difficulties, which brings us to rare sugars like allulose, which are natural sweeteners with low or zero calories and a sugar-like taste. For those of you who haven't heard of allulose, it's been through a bit of rebranding, just like rapeseed oil morphed into canola, forcing municipalities to update their town slogans. Allulose used to be called psychos, a sugar you may not want to eat in the shower. The name psychos is derived from the antibiotic from which it was isolated. That's a strange origin story for a sweetener. In the frontiers of bioengineering and biotechnology, emphasis is placed on the fact that allulose is a real unnatural sugar, rather than artificial. But ironically, if you look at the reference they cite, it talks about how allulose is made via functionalized polyhydroxyalkanoate nano-beads decorated with D-tagotos-3, a Pimmerase DTE produced in recombinant endotoxin-free branded bacteria. And now, technically, allulose is a natural sugar, a so-called rare sugar, which has been defined by the International Society of Rare Sugars, as sugars that are present in limited quantities in nature, but recent technological advances, such as enzymatic engineering using genetically modified microorganisms, now allow manufacturers to produce otherwise rare sugars like allulose in substantial quantities. But small amounts have pre-existed in the food supply, so the FDA granted it generally recognized as safe status. But it's been like really small amounts, like a few dozen milligrams, or a quarter of a quarter of a quarter of a teaspoon. See, allulose is generated when fructose is heated, and allulose is created incidentally in the process by which high fructose corn syrup is made. So, basing the safety of allulose on the fact that it's already been present in the food supply isn't very convincing. You don't know if it's safe until you put it to the test. Unlike table sugar, allulose is safe for the teeth, isn't apparently metabolized by cavity-causing bacteria to make acid and build up plaque. It doesn't raise blood sugars, even in diabetics. It can be labeled as having zero calories, though technically it may have like one and a half calories per teaspoon, similar to what you see with erythritol. Also like erythritol, it's only about 70% as sweet as table sugar, but has almost the same taste, performance, and texture as regular sugar. Are there any toxicities? Allulose is considered a relatively non-toxic sugar. What does that mean? Well, in pets we know a sweetener called xylitol can be extremely dangerous in dogs, as little as a half teaspoon and a 30-pound dog can be life-threatening, whereas a similar dose of allulose apparently wouldn't be a problem, though like over a half cup at a time could make them sick. This was a single-dose study, though. The long-term safety of allulose was tested over a period of a few months and didn't seem to cause any harmful effects at a dose of about one and a half teaspoons a day for healthy 30-pound dogs. In fact, their cholesterol actually went down, leading the investigators to suggest clinical studies to see if it's something vets should start prescribing for overweight pooches. What about in people? When the dose of allulose was gradually increased to identify the maximum single dose for occasional ingestion, no cases of severe gastrointestinal symptoms were noted until a dose of 0.4 grams per kilogram of body weight was reached, which could be about 7 teaspoons, with severe symptoms of diarrhea noted once you get up around 9 teaspoons. And you say, who can eat that much sugar at a time anyway? A single can of Coke has 10 teaspoons, and a bottle of Mountain Dew is nearly twice that. So, allulose is clearly not suitable as a standalone sweetener for sugary beverages. In terms of a daily upper limit given in smaller doses throughout the day, once you eat around 17 teaspoons a day, depending on your weight, people start getting severe nausea, abdominal pain, headache, diarrhea. So, people should probably stay under single doses of about 7 teaspoons and not exceed around 15 for the whole day. The average American may be getting 17 teaspoons of added sugar a day, so it's certainly not something the food industry can completely switch over to. In this way, allulose is close to xylitol in terms of maximal single dose, whereas the average weight man in the U.S. could get away with 14 teaspoons of erythritol at a time and the average woman 15 teaspoons. Still not enough to sweeten a bottle of Coke, but offers a little more leeway for sweetening tea or sprinkling on a grapefruit or something. Allulose is claimed to provide health benefits, though, compared to erythritol. Fourth generation sweeteners like Allulose are said to have an advantage, additional functions. We'll find out if that's true. Next. Allulose is a kind of low-calorie sugar naturally existing in very small quantities, but now industrially produced as a commercial sweetener. Said to have advantages that make it comparable to erythritol as a sugar substitute. It's said to have anti-diabetic effects, but this was in obese mice. Allulose decreases LDL cholesterol levels in high-fat-fed hamsters, and is said to have a substantial impact on obesity in lard-munching mice. But what about men and women? In a Petri dish, Allulose inhibits fat cell precursors from maturing into fat cells and reduced the amount of fat accumulation within fat cells. Therefore, the researchers conclude Allulose may be a promising sugar substitute for an anti-obesity diet, but you don't know until you put it to the test. They gave people about a teaspoon of Allulose a half hour before eating a meal, and compared to the no sugar control group, the Allulose group started burning more fat. The researchers concluded that Allulose enhances after a meal fat burning, indicating there could be a novel sweetener to control and maintain healthy body weight through enhanced energy metabolism. Okay, but first of all, it was only 15 calories of fat burned over that four-hour period, and they didn't burn more calories overall. They just switched from burning carb calories to fat calories, and so may have just switched back later on and made up for it later in the day. You can't just look at one meal. You need to track people's actual weight over time, and here we go, a weight-reducing effect of a syrup that included about 5% Allulose compared to high-fructose corn syrup. The results show significant decreases in body weight, body fat, and waste circumference, but it was some proprietary syrup mixture and it didn't look anything would look good against high-fructose corn syrup. Evaluating the effect of Allulose for fat mass reduction in humans, over 100 individuals randomized to a placebo control, sucralose, or a teaspoon of Allulose twice a day, or one in three-quarter teaspoons twice a day, and despite no change in physical activity or calorie consumption between the two groups, body fat was significantly decreased following Allulose supplementation. They even took CT scans so they could tell where the fat was disappearing from. Now, the drop in body fat was only about 2 pounds over 12 weeks, and the drop in abdominal fat in the higher-dose group was almost totally a drop in subcutaneous fat, the flabby superficial fat, not the dangerous visceral fat deeper down that really matters for health. But still, body fat lost despite no change in calorie intake, similar to what was seen in the mice, but the hamster effect did not materialize no significant change in LDL cholesterol in either of the Allulose groups. What about the purported anti-diabetes effects? If you have people chug a beverage with up to about two teaspoons of Allulose alone, previously known as psychose, or with a big load of rapidly-digesting carbs, the Allulose alone has predictably no influence on blood glucose or insulin concentrations, yet when you consume Allulose along with the refined carbs, there is actually a suppression of the elevation of blood sugar and insulin, and by a significant amount, a 30% drop in blood sugar and insulin levels over a two-hour period. We think it's because the presence of Allulose impairs the absorption of sugar through the intestinal lining, because they all might be competing for the same sugar transporter. Yeah, but who's chugging maltodextrin? What about just like a regular meal? And in borderline diabetics, who could use some blood sugar spike suppression? A randomized double-blind placebo-controlled crossover experiment to see what drinking one and a quarter teaspoon of Allulose in a cup of tea with a meal would do, and indeed a significant drop to only about 15%. You can see how they tried to exaggerate the y-axis. They also did a second experiment, randomized people to a little over a teaspoon of Allulose three times a day with meals for 12 weeks. Nice to see there didn't appear to be any adverse side effects, but they also didn't find any weight loss effects in contrast with that other study. So the body fat data is mixed, and so too is the sugar data. This study found no effects of Allulose on blood sugars in healthy participants, though a similar study on diabetics did. A systematic review of meta-analyses of all such controlled feeding trials suggests that the acute benefits on blood sugars was of borderline significance, and it's unclear whether or not this alone could translate into meaningful improvements in blood sugar control over time, so maybe it's not enough to just add Allulose, you might actually have to also cut out the junk. Although ability to suppress blood sugar responses is one of the most well-studied aspects of Allulose, I do just want to cover one last angle. The fact that Allulose extends the lifespan of a tiny roundworm called C. elegans through a dietary restriction mechanism, even though they ate the same amount of food. Two months in, just a few percent of the control group were still alive, whereas twice as many in the low Allulose group, and about 25 percent still around in the higher Allulose group. We think it worked boosting the expression and activities of antioxidant enzymes in the body, extending lifespan by mopping up free radicals. Who cares about the survival curves of worms? Well, C. elegans is a well-studied model of aging and longevity, but mostly just for convenience sake, but does share most of the longevity genes or pathways we're interested in. Be nice to see experiments on at least human cells, and here we go. The effect of Allulose on free radicals and oxidative stress in human coronary artery endothelial cells, the cells that line the inside of our arteries, add a bunch of sugar, and free radical levels shoot up, but add the same amount of sugar along with some Allulose, and it's as if you never even added the sugar, and this then translates to inhibiting the expression of an inflammatory marker that plays a role in the build-up of atherosclerotic plaque. However, it's still too early to draw conclusions about the clinical relevance of these data. To conclude, are these rare sugars like Allulose healthy alternatives for traditional sweeteners? Well, considering the variety of potentially beneficial effects of Allulose, without known disadvantages from metabolic and toxicological studies, Allulose may currently be the most promising rare sugar. But how much is that saying? We just don't have a lot of good human data. As a result of the absence of these studies, it may be too early to recommend rare sugars for human consumption. We would love it if you could share with us your stories about reinventing your health through evidence-based nutrition, go to nutritionfacts.org slash testimonials. We may share it on our social media to help inspire others To see any graphs, charts, graphics, images, or studies mentioned here, please go to the nutritionfacts podcast landing page. There you'll find all the detailed information you need, plus links to all the sources we cite for each of these topics. 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