Sweetener Side Effects

Today, we look at the not-so-sweet side of sweeteners. And, we start with one called “erythritol.” 

It’s funny; when you search for information about the low-calorie sweetener erythritol in the scientific literature, you stumble across papers like this, describing a use for erythritol that I had not imagined. But you think that’s explosive? What about headlines like these? Erythritol associated with increased body fat in young adults, metabolic dysfunction, coronary heart disease, heart failure, pre-diabetes, full-blown diabetes, and diabetic complications like kidney damage and blindness. 

But wait, I thought erythritol has been reported to be a totally safe and even have anti-oxidant properties. Let’s take a closer look at these studies.

Upon entering college, many young adults experience weight gain—the dreaded “freshman 15”—which can start them off on the wrong course in life in terms of developing chronic illness. But not all freshmen do; so, researchers wanted to try to tease out why some gained weight and others didn’t. So, on one of their first days at school, a bunch of students got their blood drawn, and then nine months later were reweighed and got more blood taken. About a quarter of the students maintained a stable weight, but the other three quarters gained an average of about nine pounds. Then, they did something interesting. They pooled the blood of all those who remained stable, and compared that to the collection of blood from all the gainers to see if they could pick out any differences. And the ones who gained weight had significantly higher levels of erythritol in their blood, and not just by a little—15 times higher levels. Those found to have poor blood sugar control had 21 times higher blood erythritol levels.

And the same thing with heart disease. What did people who developed heart disease have more in their blood than those that didn’t? Erythritol. The same thing with diabetes and diabetes complications. Okay, so what’s going on? Is erythritol contributing to obesity, heart disease, and diabetes, or is it just an innocent bystander? Maybe it’s reverse causation, meaning instead of erythritol leading to more weight gain, maybe weight gain led to more erythritol. After all, that’s who tends to go for the low-calorie sweeteners. But wait a second. In this study, for example, they took blood before and after a period of over 20 years. Was erythritol even around back then? The first blood draws were in the 80s, and erythritol wasn’t approved until 2001. It’s the same thing with the heart disease study. The blood samples were taken in the late 80s. So, the presence of erythritol in their blood cannot be explained by consumption of erythritol as a sugar replacement. So, wait. How did they end up with so much erythritol in their system?

Their own body made it. We know that your body can take excess blood sugar and convert it into erythritol. If you give people radioactively labeled sugar, within two hours radioactively labeled erythritol shows up in your blood. It turns out erythritol is a pentose-phosphate pathway metabolite, meaning that’s the pathway by which blood sugar is converted into erythritol. And the pentose-phosphate pathway is a protective pathway. It’s a way your body disposes of excess blood sugar by trying to convert the sugar to other things to bring down blood sugar levels. So, having erythritol in your system seems to be a consequence of too high sugars––not the cause. So, no wonder erythritol is associated with diabetes. That may be just like saying high blood sugar levels are associated with high blood sugar levels. And high blood sugars are also associated with obesity and heart disease.

In fact, erythritol synthesis could be an adaptive mechanism to counter the oxidative stress induced by obesity and high blood glucose. In other words, not just a way to reduce blood sugar, but since erythritol can act as an antioxidant, maybe your body is making it specifically to help sop up the mess.

The bottom line is that there are no studies linking the consumption of erythritol to any disease outcomes. But the flip side of that is yeah, the studies that have been done on erythritol do show it to be relatively innocuous and possibly beneficial, but the effects of chronic erythritol consumption have not been evaluated either way.

That’s where the science was, until 2023 when a prestigious lab out of the Cleveland Clinic found increased clotting susceptibility in human blood in a test tube and mouse blood in a mouse artery. That was at blood concentrations like 45 micromoles, or even 290. But have people chug two tablespoons of the stuff and erythritol blood levels jump up into the thousands within a matter of minutes, and so until we have clinical studies exonerating the stuff, I would recommend people to stay away from erythritol.

Next up, we look at the conflicting data on the intake of aspartame, sold as NutraSweet, with respect to non-Hodgkin’s lymphoma, multiple myeloma, leukemia, and pancreatic cancer.

The approval of aspartame has a controversial history. The FDA Commissioner concluded that there was “reasonable certainty that human [exposure] of aspartame…[would] not pose a risk of brain damage resulting in mental retardation, [hormonal] dysfunction, or both; and…will not cause brain tumors.” However, the FDA’s own Public Board of Inquiry withdrew their approval over cancer concerns. “Further[more], several FDA scientists advised against the approval, citing [the aspartame company’s] own brain tumor tests.” The Commissioner approved aspartame anyway, before he left the FDA, and enjoyed a “$1,000/day” consultancy position with the aspartame company’s PR firm. Then, “the FDA…actually prevented the National Toxicology Program…from doing” further cancer testing.

So, we were left with people battling over different rodent studies, some of which showed increased cancer risk, and some of which didn’t. Reminds me of the whole saccharin story, where it caused bladder cancer in rats, but not mice, leaving us with unanswerable questions like: so, are we more like a rat or a mouse? We obviously had to put the aspartame question to the test in people, but the longest human safety study lasted only 18 weeks. We needed better human data.

Since the largest rat study highlighted lymphomas and leukemias, the NIH-AARP study tracked blood cancer diagnoses. And, “[h]igher levels of aspartame intake were not associated with the risk of…cancer.” It’s a massive study, but was criticized for only evaluating relatively short-term exposure; people were only studied for five years. Hey—better than 18 weeks. But, how about 18 years?

All eyes then turned to Harvard, which started following the health and diets of medical professionals since before aspartame even came on the market. “In the most comprehensive long-term [population] study to evaluate the association between aspartame intake and cancer risk in humans,” they did find an “association between [both] diet soda and total aspartame intake and [the risk] of [both non-Hodgkin’s lymphoma] and multiple myeloma in men and leukemia in both men and women.”

Okay, but, why more cancer in men than women? A similar result was found for pancreatic cancer and diet soda, but not soda in general. In fact, the only sugar tied to pancreatic cancer risk here was the “milk sugar lactose.” It was the diet soda. So, the female/male discrepancy could have just been a statistical fluke. But, they decided to dig a little deeper.

Aspartame is broken down into methanol, and the methanol is turned into formaldehyde, “a documented human carcinogen,” by this enzyme here, alcohol dehydrogenase. The same enzyme that detoxifies regular alcohol is the same enzyme that converts methanol to formaldehyde.

Is it possible men just have higher levels of this enzyme than women? Yes, that’s why women get higher blood alcohol levels drinking the same amount of alcohol. If you look at liver samples from men and women, there’s significantly greater enzyme activity in the men. So, maybe that explains the increased cancer risk in men—the higher conversion rates from aspartame to formaldehyde. But how do we test it, though?

Well, ethanol—regular alcohol—competes with methanol for this same enzyme’s attention. In fact, regular alcohol is actually “used as an antidote for methanol poisoning.” So, men who don’t drink may have higher formaldehyde conversion rates from aspartame if this whole formaldehyde theory is correct, and indeed, consistent with this line of reasoning, it was the men that drank the least alcohol that appeared to have the greatest cancer risk from aspartame.

A third cohort study has since been published and found no increased lymphoma risk associated with diet soda during a ten-year follow-up period. So, no risk detected in the 18-week study, the 5-year study, or the 10-year study—only in the 18-year study. What should we make of all this?

Some have called for a “re-evaluation” of the safety of aspartame. The horse is kind of out of the barn at this point, with “34,000,000 pounds” of the stuff produced annually, but that doesn’t mean we have to eat it—especially, perhaps, pregnant women and children.

Finally today, the natural plant-based sweeteners stevia and monk fruit (Luo Han Guo) are pitted head-to-head against aspartame and Splenda.

A number of artificial sweeteners have been FDA-approved in North America, including aspartame and sucralose (sold as Splenda). But, there are also natural high-intensity sweeteners found in plants. The global market for non-nutritive sweeteners in general—these non-caloric sweeteners—is in the billions, including all the artificial ones, “and two natural [ones] extracted from plants…stevia…and monk fruit.” I’ve done a video about stevia; what about monk fruit?

“The fruits of Luo Han Guo [monk fruit in Chinese] have [evidently] been used for hundreds of years as a natural sweetener and…folk medicine. “The non-caloric sweet taste [comes from] mogrosides, a group of cucurbitane-type triterpene glycosides that [make up] about 1% of the fruit,” and are like hundreds of times sweeter than sugar.

“The mixed mogrosides have been estimated to be about 300 times as sweet as [table sugar], so that an 80% extract was nearly 250 times sweeter than sugar.” If you read reviews in Chinese natural medicine journals, you’ll see pronouncements like this: monk fruit “has been shown to have anti-coughing effects, anti-asthma…, anti-oxidation, liver-protection, [blood sugar]-lowering, immunoregulation, and anti-cancer.” But, what they don’t tell you up front is that they’re talking about reducing ammonia-induced mouse coughs.

“A natural food sweetener with anti-pancreatic cancer properties.” Monk fruit “may be used for daily consumption as an additive in foods and drinks to prevent or treat pancreatic cancer.” Yeah, maybe in your pet mouse. And, the “[a]nti-proliferative activity of…monk fruit in colorectal cancer and throat cancer” was on colorectal and throat cancer cells in a petri dish. Now, they did show mogrosides killing off colorectal cancer cells and throat cancer cells, and our digestive tract could be directly exposed to these compounds if we ate them, but what’s missing? Right, they didn’t test it against normal cells. You could pee in a petri dish and kill off cancer cells. The whole point is to find something that kills off cancer but leaves normal cells alone, something that they weren’t able to show here.

Are there any human studies on monk fruit? No,…until, now. “Owing to the rapidly growing popularity of natural plant-[based sweeteners],” they thought it would be “of interest to determine whether natural [sweeteners] would be a healthier alternative to sugar [or] artificial [sweeteners].” So, they randomized people to drink an aspartame-sweetened beverage versus monk fruit-sweetened, versus stevia, versus table sugar. Then, they measured blood sugars over 24 hours, and there was “no significant difference…found” between any of them.

But, wait a second. The sugar group was given 16 spoonfuls of sugar, the amount of added sugar in a 20-ounce bottle of Coke; so, the other three groups consumed 16 fewer spoonfuls of sugar, and still had the same average blood sugars? But, table sugar causes a big blood sugar spike. Drink that bottle of sugar water with its 20 sugar cubes’ worth of sugar, and your blood sugars jump 40 points over the next hour. Whereas, you give them an aspartame-sweetened beverage, or monk fruit, or stevia, and nothing happens—which is what you’d expect, right? These are non-caloric sweeteners: no calories. It’s just like you’re drinking water, right? So, how could your daily blood sugar values average out the same? The only way that could happen is if the non-calorie sweeteners maybe made your blood sugar spikes worse somehow later in the day?

You give people Splenda mixed with sugar water. You get a greater blood sugar spike, a greater insulin spike chugging the sugar with sucralose than without, even though Splenda alone causes no spike of its own. So, does aspartame do the same thing? At the one-hour mark, they fed people a regular lunch. And, so, the blood sugars went back up and down as they normally would after a meal. Not spiking as high as drinking straight sugar water, just a gentle up and down. Okay, but that was in the group that drank the sugar an hour before. In the group that drank the aspartame, even though their blood sugars didn’t rise at the time, an hour later at lunch, they shot up higher, as if the person had just drank a bottle of soda.

Okay, but what about the natural sweeteners, stevia and monk fruit? Same thing. Same exaggerated blood sugar spike to a regular meal taken an hour later. So, you can see how it all equals out in terms of average blood sugars, even though in these three non-caloric sweetener groups, they took in 16 spoonfuls less sugar, at least in part because they ate more. After drinking a Diet Coke, you’re more likely to eat more at your next meal than drinking a regular Coke. In fact, so much more that the energy ‘saved’ from replacing sugar with non-caloric sweeteners “was fully compensated for at subsequent meals; hence, no difference in total daily [calorie] intake was found.”

“The [sugar]-sweetened beverage led to large spikes in [both] blood [sugar] and insulin…, whereas these responses were higher for [the three other] beverages following the…lunch later.” So, when it came to calorie intake, or blood sugars, or insulin spikes, they were all just as bad.