what's up guys back with another educational video and this week just when you thought it was safe to take in artificial sweeteners again a new studies published but first like the video subscribe to the channel and leave a comment for the algorithm i know when this study got published because it got sent to me by no less than probably a hundred people and i know andrew huberman tweeted about it and actually uh tagged me in it and so i had had a chance to look at it until just today it is a pretty cool study
to be honest so this study was published in cell cell is a reputable journal although i will say i have read some absolute crud get published in cell now i don't think this study was corrupt i think it was actually pretty good but study out of israel and what they did was compared four different artificial sweeteners or actually technically not artificial because they included stevia so they called it non-nutritive sweeteners so they compared sucralose aspartame saccharin and stevia they were looking at the gut microbiome they were looking at insulin glp1 and they actually looked at
a bunch of different tca cycle intermediates and some stuff that we're not going to cover because it's just too technical and we lose the main theme of this paper so they were comparing these non-nutritive sweeteners good good first step humans and they were in dosages that are within the acceptable daily intake range so they weren't just like blasting people with super high doses that's also a good check mark in this study's corner the other thing was they had over a hundred people in the study so for a randomized control trial it was well powered which
a power calculation is basically you look at what we hypothesize will be the difference if we want to detect that difference based on the variability that's seen in these various studies looking at these markers how many subjects are we going to need in order to be able to detect that difference and so that's kind of the basis of a power calculation so i looked at the power calculation it was solid and the amount of people they recruited for the study was good basically they had people kind of run in on a baseline for seven days
and then for two weeks had them either consume one of the four artificial sweeteners and they made a big point to say that there was glucose used in the sachets as a bulking agent so some of you guys may not know but if you look at like a patch of say sucralose or aspartame or whatever if you look in the packet it'll actually say like glucose or maltodextrin that is used as a bulking agent because the amount of non-nutritive sweetener you need is so small that it would be like just a couple granules so you
need to put in like a bulking agent with it otherwise you'd be like checking to see if you've poured out like these few little granules into your into your coffee or whatever it is so each person was consuming around five to six grams of glucose per day in addition to the non-nutritive sweeteners so another good thing they did was they had a group that just consumed sachets of glucose to match the glucose intake of the other participants very very smart good point because if they hadn't done that i would have called upon it then they
also had another group they got no glucose and no non-nutrients of sweeteners so just kind of a completely basal control group a control group that standardizes for the glucose and then your test groups and they consume those for two weeks and then they had a one-week washout period as well now what's funny is the people who love to dismiss data that does not fit with their bias when they hear two-week study they go oh it's two weeks ah the same people sending me this study like see artificial sweeteners or non-nutritive sweeteners are bad for you
it's like well what happened to the whole two weeks thing point is for what the researchers were testing i think two weeks was a reasonable period of time they were looking at blood glucose responses they were looking at insulin responses they were looking at gut microbiome which two weeks is typically enough time to see changes in the things they wanted to measure now one of the things they measured for example was hba1c which didn't change in any group which is not surprising because hba1c really you need at least kind of three months if not more
to see differences in whatever you're testing for their primary outcome data the amount of time that they did the study i think was reasonable so i'm not going to ding them on that now obviously if they could have done it for a longer period of time great but they didn't and that's okay and again here's me someone who has i don't wanna say defended non-nutritive sweeteners i've just not allowed people to make claims about them based on nonsense but here's me who a lot of people would look at as a pro non-nutritive sweetener person saying
hey the study duration is not something we can really ding them on because for what they wanted to test it was totally fine even though the outcomes of the study may not be in favor with what i have previously said but we're going to get to that so they had them also wear continuous glucose monitors and they did oral glucose tolerance tests where they challenged them with a load of oral glucose and then saw how long it takes to clear it and they did a calculation called the incremental area under the curve of glucose which
is basically looking at what is the total area under the curve for the glucose response which i think is one of the better ways to measure acute glycemic responses because one you're measuring it in response to an actual challenge of glucose and two you're looking at the total area under the curve you're not just looking at isolated time points so i think that's a great thing to measure like i said they looked at a lot of tca cycle intermediates and they looked at a lot of species of gut microbacteria and one other really unique thing
about this study was they took great care to only include people who had never used non-nutritive sweeteners and they did a very thorough dietary recall to make sure that this was accurate so for example they had a lot of people volunteer i think it was like 1500 that they screened but only about 130 were actually able to start the study because most of those people were unknowingly consuming non-nutritive sweeteners because it's in so many things in some ways it's a strength that they're doing that because when you have people who have never consumed them before
you can be sure that these acute effects that you're seeing are due to what you're doing in your study rather than things that may have happened previous to that here is the one big downside for people to be able to say they've never consumed non-nutritive sweeteners even unknowingly because most people consume some unknowingly i would say there's a high probability those people were purposefully avoiding non-nutritive sweeteners likely because they feel that they are deleterious to health additionally it's impossible to blind these people from knowing whether or not they're consuming glucose or non-nutritive sweeteners because like
the first time you've ever had a diet coke you're like oh man that tastes different than a regular coke so these people are going to know what they're taking in and it's a probability that they already have a negative association with those non-nutritive sweeteners now i'll get into a few kind of limitations of the study and criticisms a bit later but let's go through the results so looking at the oral glucose tolerant tests and the incremental area under the curve of blood glucose they did see an increase in blood glucose with sucralose and saccharin that
was a pretty modest increase it wasn't very big but it was a difference that was statistical stevia and aspartame had no effect on blood glucose what's interesting is they did not see an increase in insulin nor an increase in glp-1 in any of these groups so that was interesting here's where i'm going to get into some criticisms the participants were wearing continuous glucose monitors and the oral glucose tolerance tests were not performed by the researchers they were not supervised by the researchers they gave the subjects kits and instructions on how to do the oral glucose
tolerance tests to me this is a major problem the reason being this is one of your primary outcome pieces of data it's literally in the title glucose tolerance is in the title and you left it to people to do at home on their own accord the pushback would be well they're wearing continuous glucose control monitors they were given you know specific instructions and they were given the solutions of glucose to just take you know that sort of thing i don't really care when it's your primary outcome data that needs to be supervised in my opinion
because if you've got people who have been specifically avoiding non-nutritive sweeteners for basically their entire lives it's likely they have a negative perception of them and they cannot be blinded to it they know the people who are taking in probably know they are taking it and in that group what is to stop them from taking the glucose solution as well as a little bit extra now am i saying that happen i don't know i don't know what happened that's the point you don't know because the researchers did not supervise it these results could be completely
legitimate but unfortunately because they had them do them from home to me it really calls into question the legitimacy of the results from the glycemic response is there any reason it shouldn't have worked no but i just know how much care we took on testing days when we were looking at human data there was so much care taken to make sure we got it right because it's so easy to get it wrong even when you have the researchers there letting people do it on their own just introduces all kinds of potential sources of air so
to me i have a real problem with this glycemic data because i just don't know if we can trust it especially because there's no differences in insulin like how does that happen i guess you could say well somehow it raised their blood glucose but must have blunted their insulin i'd be interested to see the mechanism behind that i'm not saying that this stuff happened i'm just saying unfortunately since they weren't supervised you can't be sure and the other thing is placebo the power of placebo is very real we know this we know that the power
of suggestion the power of a pre-existing belief can actually change your physiology it is completely plausible that people who had completely avoided non-nutritive sweeteners because they thought they were bad for them if they're now taking them in that they're actually having somewhat of a stress response to taking them in because they're worried about what it's doing to their body potentially if you're having a stress response and elevate your cortisol you can absolutely elevate your blood glucose as well now again they didn't measure cortisol so we don't know that for sure i'm not saying that's what
happened i'm just saying we don't know but it is a plausible explanation for what we're seeing here finally let's say that this data is all legitimate and my criticisms are things that we don't need to be worried about they didn't happen you know those sorts of things that's totally fine uh and by the way i do think this study overall is pretty darn good every study has limitations i'm not trying to dog it i'm just really wanting to point out that as a piece of primary outcome data this should have been supervised by the researchers
in my opinion but let's say all my criticisms are wrong and this this data is completely legitimate totally fine it's 14 days and so we have to keep it all in balance with the consensus of the data which there are meta-analyses now demonstrating that when you compare non-nutritive sweeteners to sugar-sweetened beverages non-nutritive sweeteners improve glycemia they lower blood glucose they reduce body weight and they have several positive effects on hard health outcomes and even when you substitute non-nutritive sweeteners for water there was a network of meta-analysis that looked at this that showed compared to water
non-nutritive sweeteners had a slight effect on lowering body weight and they did not make any measures of glycemic control worse so okay you've got this continuous glucose monitor on for over the course of 14 days you see some effects on postprandle blood glucose okay but it doesn't seem at least as of yet to show up in long-term assessments of glycemia it does not seem to affect long-term glycemia based on the outcome data from human randomized control trials and i'll link a bunch of them in the description not saying it's not wrong i'm just saying when
we go to the actual randomized control trials in humans where they look at hard outcomes like body weight hba1c insulin sensitivity they don't see decrements when using non-nutritive sweeteners compared to sugar sweetened beverages especially and even water and they see reductions in body weight and improvements in health markers especially when substituted uh for sugar sweetened beverages so again am i saying that you should go out and drink beverages sweetened with non-nutritious sweeteners rather than just water no i'm not saying that but if you're somebody who really struggles with sweet tooth and drinking sodas i can
tell you that taking in non-nutritious sweeteners a hell of a lot better than drinking regular soda or sugar sweetened beverages and that is clear based on the long-term hard outcome human randomized control trials so again not saying this stuff doesn't matter at all i'm just saying we need to keep it in the proper perspective on balance non-nutritive sweeteners in the long term show positive effects on glycemia when substituted for sugar sweetened beverages and even when compared to water don't appear to have negative effects on glycemia in the long term and i'm just trying to reconcile
the difference in these data sets because this is showing an effect whereas long-term stuff doesn't perhaps there's an initial adaptation period with things like sucralose or saccharin and then once you've become adapted to it you don't have that increase in glycemic response so they measured a bunch of metabolites as well as a bunch of different species of bacteria from the gut microbiome and did see changes now this is where it gets really tricky because people say oh my gosh their gut microbiome changed that's a bad thing we don't know we do know that if you
change almost any aspect of your diet your gut microflora will change it's very responsive what we don't know is whether or not that change is a good or bad change and i'll give you an example so from the paper they said there were 22 metabolites that were correlated with an increase in the area under the curve of glucose okay so basically the people consuming these non-nutritive sweeteners had higher levels of these metabolites and that was correlated with their increase in glycemic response so these metabolites should be bad right well the metabolites were the short chain
fatty acids propionate butyrate and valerate so i looked up and i'll link some studies in the description when they supplement people with propionate and butyrate they actually get better effects on glycemic response and they appear to have some other beneficial impacts as well so again we're balancing all right you're shifting to forms of gut microbiota that produce more butyrate and propionate but is that necessarily a bad thing this paper kind of is saying well maybe it's a bad thing but then we've got other papers saying no it's a good thing we just don't know enough
about the gut microbiome to really be able to say for sure and that's why i continue to default to what does the hard long-term human outcome data say for non-nutritive sweeteners and right now it's favorable so another example of this is in the aspartame group b fragilis was positively associated with the increase in the area under the curve of blood glucose okay well that must mean b fragilis is bad and giving aspartame increases that particular bacteria and so that's why we don't want aspartame except when you look at the research on b fragilis there's some
research showing it actually decreases intestinal inflammation so it seems to have some positive effects as well so again all this to say we just do not know enough about the gut microbiome to be able to make some of these strong statements now i'm not saying we shouldn't do more research on this stuff we absolutely should but again when i make recommendations i am looking at the consensus of the data we have quite a few studies out there on non-nutritive sweeteners and hard health outcomes like body weight body fat hba1c and a whole host of other
hard endpoint markers until i see evidence that non-nutritive sweeteners are negatively affecting those in the long term i'm going to continue to say that non-nutritive sweeteners are a reasonable tool for people to use am i saying they're metabolically inert it doesn't appear so it doesn't appear that we can say that they're metabolically inert but we don't know if that's a bad thing or a good thing right now on balance i would say it doesn't appear to go either way although hard human outcome data would suggest they're positive but mostly because people just consume less calories
is this paper a negative for non-nutritive sweeteners i suppose a little bit when i saw the title and i saw how people were sending it to me i was like oh man this seems like it's going to be really bad but again once you like read the full text of the paper i'm like okay well they saw some modest differences in you know glycemia in a couple of the groups but then when you go dig through the data a little bit more and you look at the hard human outcome data it doesn't seem to line
up with those long-term outcomes that we're seeing so it could be that this is simply an initial response during those first few weeks of consuming a brand new element to the diet that these people have never seen before again they've never consumed these before and then the body adjusts and now there's no difference you know in 10 12 however many weeks that could explain the difference between the short-term data and the long-term data but we just don't know we obviously need more studies on this hopefully they'll repeat a study like this in a population of
people who have already been consuming non-nutritive sweeteners and hopefully they'll do more research and people who have never used them i don't want to ding the study for using that population because i think that's a reasonable question to ask the downside is to how that's going to be interpreted by the mainstream media and many of you and again if people have never consumed them because they're in so many things that suggests that they were purposely avoiding them and you cannot discount the power of placebo they have shown the power of suggestion the power of placebo
can be just as powerful as actual pharmaceutical drugs in some cases many people will say oh well you can't placebo me because look that you know they're actually showing differences in blood glucose placebo is not a feeling sure you can be placebo and think you're feeling something that's not actually happening but they've shown that placebo actually can affect physiology when your brain believes something to be true it can actually affect the physiological outcomes so again a plausible explanation to this is that these folks were more stressed by consuming non-nutritive sweeteners because they've been avoiding them
and they think they're bad for them and so they have some kind of stress response and that raises their blood glucose that could be complete hogwash i'm not sure but the point is this specific population we need to keep in mind when we're analyzing this paper because this is a brand new population that's never really been assessed before when it comes to non-nutritive sweeteners my take home here is if you are consuming non-nutritive sweeteners just for the heck of it and you don't mind drinking water and you don't have any cravings for you know soda
or whatnot then okay you can just do water fine but if you're somebody who these specific non-nutritive sweeteners have allowed you to consume less calories by cutting out sugar sweetened beverages i would not cut them out based on this study i don't think the data is nearly strong enough for that and again on balance looking at the long-term hard human health outcome data they seem to be a net positive all right guys hope you like this video if you like deep dives like this into research studies make sure you check out reps which is research
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