Is this Yale sucralose study legit?

I use Splenda because I have reactive hypoglycemia. I’ve had it since my mid-20s. These are my bona fides, so you know I’m not one of those people who read and article, and decided I had hypoglycemia because I get cranky when I’m hungry: I was diagnosed by a doctor after he had me check my blood sugar regularly with a glucometer 5x/day for a month, and confirmed by both a check of A1C, and a glucose tolerance test. (If you don’t want the long story, skip to the arrow.)

If you don’t know, a glucose tolerance test consists fasting for 12 hours, having a baseline blood draw, drinking what tastes like pure glucose, then having 8 blood draws with a finger-stick each time for a glucometer check. After the sixth blood draw, my blood glucose level was 25. 90-100 is normal for a fasting non-diabetic (who was previously eating normally). 0 is dead. Diabetics shoot up as high as 500 sometimes after the glucose drink. I never went higher than 115, and my second draw was already something like 80. Normal non-diabetics can go as high as 140, and come down slowly. They don’t go lower than about 85.

They called my doctor after the sixth draw, and he said the halt the test and send me to the ER for an IV drip with something to raise my blood sugar slowly, and something to eat with complex carbs and protein.

My point is, that my pancreas does not function correctly. Right now, it is sort of doing the opposite of what a diabetic’s would, but that is actually besides the point.

On my father’s side of the family, there is a heritable form of adult-onset (age 50-70) insulin-dependent diabetes. Clinically, it looks just like “juvenile” diabetes, but clearly it isn’t, with a middle age to elderly onset.

The cause appears to be autoimmune. There’s no treatment, other than to manage it as diabetes.

My doctor tells me that I am at especially high risk for it because of the hypoglycemia. A pancreatic malfunction of one manifestation, could come to manifest another way.

–> My point, and I do have one, is that after having reactive hypoclycemia from age 26, or thereabouts, to whatever age I am when my pancreas finally gives up, and I become insulin-dependent, and then live however many years that way, is likely to shave time off whatever potential lifespan my genes bestowed upon me.

Just an illustration of the fact that any group of people using Splenda long-term is probably going to include people with pathologies, so it’s going to be very hard to tease out the effects of Splenda alone.

I will say that if I ate sugar like I eat Splenda, well, I couldn’t. I get terrible symptoms when my blood sugar is low. The chances that I would do something stupid, like kill myself in a car accident with a combination of poor judgment and poor motor control both caused by low blood sugar, and shave a lot more years off of my life than eating Splenda ever would are very real.

Not one related to the study, given that they specifically excluded regular consumers of non-nutritive sweeteners.

Many years ago I read a rat study (probably in The New England Journal of Medicine, because my father was a doctor and it used to lie around the house. but it was a long time ago, so I’m not sure) in which rats were either put on a diet of:

unlimited rat chow and water
unlimited rat chow and sugar water
unlimited rat chow and saccharine water

They measured the total caloric intake of the three groups of rats. The third group, who consumed saccharine, consumed the most calories. The rats who drank sugar water consumed a little more calories than the control rats, but not much, because the ate less rat chow.

The hypothesis was that the rats tasted the sweet water, didn’t feel the expected sugar-boost, and so felt hungry. That is, artificial sweeteners may mess up the link your gut and brain have between what food tastes like and what it does to you.

I wish I had a source. But I have taken this to heart, and avoided “fake foods” and tried to pay attention to how I feel, and whether my body actually wants more food. While I gained a lot of weight with each pregnancy, and I am fat, my weight has otherwise been quite stable throughout my adulthood. I believe there is some innate appetite control, and I think it’s incredibly plausible that fake sweeteners mess it up.

For more information, look into the relationship between artificial sweeteners and metabolic syndrome. For example, this recent review paper

Metabolic syndrome refers to a cluster of factors, such as high blood pressure, weight, and others which puts people at a risk of heart problems and diabetes.

When a very small study, like in the OP, finds a result it can mean several things. A few odd measurements skewed the results, and it is meaningless. The effect size is so large, that it is detected in even a small study. Either way, the answer is more studies! Seriously, there is nothing wrong with small studies if interpreted correctly, and followed up with larger studies when it seems warranted. I do not have an opinion on the merits of the study in the OP.

O really? I thought it’s the original Yale, the slave owner doing the study himself. It’s so exciting he came back from the grave!

If I wanted to get an expert (or several) opinion on this, who should ask?

Your doctor? They read these studies and have access to the full reports.

But seriously, do you need an expert to explain that a study based upon a group of only 13 people in an self reported and uncontrolled environment is meaningful?

Also, has anyone in this board actually read the report that is behind a paywall.

What do you want to know?
Is the study any good?
Should you stop eating artificial sweeteners?

The best possible study of 13 people says “do a larger study”. In an extreme case, it might say, “do x until that larger study is done, because it looks plausible.”

Honestly, based on data unrelated to that study I have been avoiding artificial sweeteners for years. But that study doesn’t shift my opinion significantly.

average doctor has ZERO clue.

yes. I want to know if it’s any good. By the way, don’t you think that if anyone here knows that 13 is a low number, that professional researchers at Yale know that and yet, went ahead with the study? Just to waste their time and make fools of themselves?

There is obviously more to this than saying “13 is a low number”.

Small studies can do lots of tests to determine what an effective way to set up a larger study might be.

Their Human Investigations Committee recommended termination due to adverse events, namely HOMA-IR elevation in that majority of the sucralose plus maltodextrin group. There’s nothing improper here AFAICT. No time was wasted and they’re certainly not the ones looking foolish here.

The reason studies require a lot of people relates to being sure of your conclusion. If the change is fairly small, you need a lot of people to increase the study power so you know the changes are not due to chance.

A study of 13 people consuming sweetener for two weeks is not going to allow any meaningful conclusions. People want to know if sweeteners are bad in the long term, not measured in this study. People who use sweeteners may be doing so because they are overweight - and may be making many other dietary choices apart from the sweetener.

Sweeteners have been studied pretty extensively and are generally safe at doses people would ingest. A small study like this will not change the needle at all. There are benefits to limiting dietary sugar (to an average of 40 grams per day) and it makes sense to limit the amount of sweetener one consumes as well. Personally, if you drink 2 or 3 diet sodas a day, this would not concern me one iota.

To be clear. The point of a small study is to see if a larger study may be warranted. You don’t want to waste the resources testing everything with huge studies, so you start small. A lot of these smaller studies are done at colleges since that’s where the researchers coming up with new ideas often are. They’ll either be professors or students doing the study for their degree.

Based on what you’ve said, this sounds like a study that warrants a larger study. Still it’s too common for things from smaller studies not to work out to say anything definitive yet.

We also saw this with COVID-19 treatments, where a small study showed promise but a larger one didn’t. People who didn’t understand how science tends to operate would sometimes say these were some sort of conspiracy, but they weren’t.

So what is suggest is that you stay on the lookout for more studies, while maybe just keeping track of you sucralose consumption and getting your blood sugar tested as often as your doctor requires.

This. Doing dietary studies is extremely difficult unless the participants are monitored 24 hours a day. In addition this particular study essentially had three experimental groups and no control.

Group 1 - sucralose only beverage
Group 2 - sucrose only beverage
Group 3 - sucralose with maltodextrin beverage

Presumably group 2 was supposed to be a type of control, but then they used maltodextrin rather than sucrose for group 3. A better study would have used sucralose + sucrose rather than maltodextrin for the 3rd group.

I’m now speculating. Most people eat a diet very high in carbs. Adding 30 more grams of sucrose per day, as in the Group 2 of this study, is unlikely to make much of a difference. My hypothesis is that the changes they saw in the maltodextrin group were due to the maltodextrin and not the fact that it was combined with sucralose. They would possibly have found the same changes in a maltodextrin only group.

From talking with my brother, research is slowly moving to this kind of complex control group, based on different and more advanced understanding of statistics.

Also the study had equal sweetness and equal or zero carb calories per dose, whereas the proposed sucrose/sucralose does not. Using sucrose instead of glucose does introduce a difference though. I don’t recall seeing any mention of that in the paper.

No need for a no-dose control here.

Perhaps equal sweetness, but it would still be obvious which was which based on taste. Non-sugar sweeteners, both artificial and natural, have a very distinct taste that is immediately obvious.

The taste difference is real but doesn’t appear to matter, given that they measure no difference in fMRI-BOLD difference maps between sucrose and sucralose at the group level, and the same correlation between insulin difference scores and BOLD-difference maps. Not so with the combo group.

They’re not trying to trick anyone here, e.g. with a placebo. This is a psych group looking at brain responses to various stimuli, one being sweetness. They get baseline scans before dosing.

What exactly is “this kind of complex control group”? I’m not seeing how it works.