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Low N is still interesting. If anything, it can help justify larger studies along the same lines, since there are costs for a study and researchers have to make their case to get the funding.
It isn't "Low N" though. 45 adults for a clinical study like this one is actually a very respectable size, particularly given their measures (and their respective reliability/studies backing them).

Seems like every study I read non-science people accuse it of having too few participants, without even considering the type of study (clinical Vs. statistical) and measures (subjective Vs. objective, reliability, literature, etc).

This is not a "Low N" study. If you believe it is then explain the statistics or methodology problems.

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Yes, that too. Also it's important to realize that each study is a datapoint unto itself, and over time these data points paint a picture. But even if the study is not the whole picture, we can still get a hint as to what that picture is shaping to be.
I can taste sucralose. It's very irritating, because it rings out as a clear bitter note with a definite aftertaste, but none of my peers have the problem, and so I look like a hypochondriac.
I can taste it in Lemonade, sweet tea, or coffee but not as much in some diet colas. I stay away from it but accidentally drink it from time to time. To me it’s so overpoweringly sweet and weird tasting I can get past it. When I was a teenager we tried to make Kool-aid with it when we were out of sugar and I never forgot the taste.
Years ago, I used to put a bunch of Splenda in my coffee. I can't believe I could stand the taste of it after trying it again recently. So sweet and chemically.
I'm the same. It seems to pierce any flavor profile. It's not the first thing I taste, but it quickly overwhelms other flavors and IMO ruins whatever it's in. I rarely read ingredients lists, but when I do, it's after tasting sucralose.
I can taste all these "sweeteners" and they all taste bitter to me. Cola Zero actually makes me wretch.

I just drink normal Cola but moderation is key. I have very few other sources of sugar and I eat mostly healthy home cooked (by me) food. Lots of vegetarian food too.

I love diet coke. Aspartame doesn't taste as close to sugar as sucralose does, but it has no lingering aftertaste.
Opposite for me. Coke zero is preferable to diet coke. (Neither are good.)
In Norwegian we have a proverb, "Smaken er som baken" which roughly translates to "The taste is like the butt", and it is implied that they are all different :)

I know people who prefer Zero or Diet to regular, but not many.

Coke Zero isn't bad - especially from a fountain it isn't lightyears from the real deal.

Diet Coke tastes like counterfeit battery acid.

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This has been hinted at before, some LCS have been measured to cause an insulin response in spite of being low or no calorie. Insulin added to the blood with no sugars to neutralize is bad for the body/can slowly cause insulin resistance.

What's also interesting is that Aspartame keeps on coming out ahead in study after study. No insulin response, no substantial side effects, and no proven cancer risk.

From everything I've read if you're only going to consume one LCS then make it Aspartame, it has had more research conducted on it than all of the others combined (and frankly most, even natural, food ingredients).

As a type 1 diabetic, I can confirm that vast quantities of aspartame do not cause my blood sugar to rise.
GPs claim was that non-aspartame sweeteners cause insulin to rise, not blood-sugar. This would cause non-diabetics to become hypoglycemic, and over a long-term could cause type 2 diabetes.
I always assumed that when I taste something sweet, my body starts putting insulin in my blood. Over time it learns how much to put in based on how sweet the food tasted. If that's true, I'd expect too much insulin for food with aspartame, BUT ALSO too little when food has real sugar, because of the long term learning.

I'd expect a type 1 diabetic not to see either effect because the system that aspartame wacks out of tune is turned off for them.

I appreciate that I have no actual knowledge on the subject, except that I know the body must have control loops for this stuff and they must be kept in calibration by some mechanism. Probably my model is too simple.

There have been studies where mice were fed a diet of various natural and non-caloric sweeteners. The mice were monitored for blood sugar levels and cholesterol as well as other measures. The mice who ate all three of the most popular artificial sweeteners had worse outcomes on several measures. There is some additional evidence that the effect is largely due to the sweeteners' effect on the composition of gut bacteria. I can't tell you if this holds up (or if it holds for humans) but aspartame does not seem to be harmless in these studies.

Popular coverage: https://www.scientificamerican.com/article/artificial-sweete...

2: https://www.businessinsider.com/artificial-sweeteners-aspart...

Link to one actual study: https://www.mdpi.com/1420-3049/23/2/367

> The dose (0.75 mg/kg body weight/day) > was 2.5× human allowed daily intake (ADI) (0.3 mg/kg body >weight/day) for neotame set by the U.S. FDA.

Neotame is 8000 * sweeter than sugar so this is the sweetness equivalent of 0.6 Kg of sugar a day or 2,348 calories for a 100kg human. This is also 8.4 * the average daily sugar consumption in the US.

Monk fruit may be promising, there has been studies in Mice where Monk Fruit even lowered blood sugar levels. However, I agree more studies must be completed.

Another study including Aspartame, monk fruit, stevia and sucrose was kind of interesting which showed sucrose (as expected) had the biggest insulin spike, but interestingly the participants made up for the sucrose calories in their next meal and actually had higher insulin spikes in the subsequent meal compared to the sucrose group. https://www.ncbi.nlm.nih.gov/pubmed/27956737

Probably best to avoid all sweeteners.

What does LCS stand for? low carb sugar?

one more q, is the insulin spike level of fake sugar similar to that of a regular sugar?

Appears to mean Low Calorie Sweetener
oh right that makes more sense thanks!
Whats absolutely wild to me is how we're learning of any of this now, despite many of the LCS's being out for decades.
Stevia tastes better and has no insulin response.
It doesn't taste better.

Now, how should we settle this dispute? Pistols at dawn?

All artificial sweeteners taste off in a bad way.
As far as I'm concerned that's the body signalling to us that we should avoid it, so I do.
That's my argument against broccoli.
I love broccoli, I wonder what that means.
I would assume that you're not a child, but as a greater point, that something you like and I dislike doesn't mean that it's necessarily going to be bad for us because I don't like it.
They all taste differently sweet. If your goal is to taste sugar, obviously sugar does so best.
No. Pistols at dawn.
Stevia tastes bitter and nasty. It's not even sweet.
I wonder if people have dramatically different sensations to artificial sweeteners like they do foods such as Cilantro or Grapefruit.
It probably is, or really just down to personal preference. Saccharin and Aspartame are awful to me, and I could never understand how anyone can touch it. Sucarlose I can handle it up to two packets. Three, and I get the same reaction as Saccharin. Stevia by itself isn't that great, either.

The only one I can use as anywhere close to a sugar substitute is Truvia, which is a Stevia/erythritol blend.

I believe so, yes.

My ex-wife used Stevia a lot and loved it. It tastes bitter and disgusting to me. Growing up, my mom always used Sweet-n-Low (saccharine sweetener) and tried to get me to use it. It always tasted bitter and disgusting to me.

I'm not a fan of grapefruit either (very bitter, no sweetness). Cilantro I'm okay with though; it doesn't taste like soap to me, but to some people it does.

It's supposed to be 100 times more sweet than sugar for the same amount, so there's that...
I think it depends on the application.

When I drink diet soda, I find that aspartame works better than splenda... and I haven't found a stevia-based soda yet that doesn't taste absolutely disqusting.

When I make a pitcher of Kool-Aid, I find that 8 packets of stevia produce a result that's better than any other sweetener I've tried (including sugar).

Taste is subjective, and varies from individual to individual, of course.

I use stevia in my trog smoothies. (Kale, ginger, coconut cream, whatever else is in the fridge.) Stevia somehow softens the sour tangy bitter acidity whatever-its-called taste of the kale.
All sweet chemicals other than sugar taste weird to me.

Stevia especially tastes like sharply-sweet chemicals. First time I tried it in orange juice I winced.

I just eat sugar as it comes in today's foods. I'm really skinny so maybe I should eat more of it?

I've never heard of sweetening orange juice. Do you not find it sweet enough on its own?
I'm quite the fan of erythritol. I do get a 'cool' aftertaste with it though.
Maybe the right answer is to not use anything that is extracted and refined, including sugar.
I like sweet things in my coffee. I also like not being overweight. Hence, sucralose in my coffee and 1000mg daily of metformin (taken for life extension purposes, second order effect is lowering blood sugar level). The right answer need not be "abstain from what you enjoy" if we can hack together a solution from diet and engineered compounds.
I like smoking a pack of cigarettes a day and eating candy bars - I'll just switch to vaping and granola bars so I can still do what I enjoy.
Can't tell if /s. Life is meant to be lived. Make healthier choices, but still enjoy. Otherwise, what's the point?
Yes, being healthy is enjoyable. Sometimes protecting ones health means not doing those things that provide superficial, temporary feelings of joy (junk food, artificial sweeteners that could lead to cancer and other health issues, smoking, etc.) that are in fact bad for our health and likely to reduce long term joy.
You can do just about anything in moderation and it won't be bad for you, short or long term. For example, having a cigarette or two a week over a few beers with some friends. Completely abstaining from superficial, temporary feelings of joy can be detrimental to some people when they finally do give into temptation.

  Life is meant to be lived.
A tautology at best, but more likely empty rhetoric.

  Make healthier choices, but still enjoy.
This assumes healthy choices cannot produce enjoyment.

  Otherwise, what's the point?
In our modern times, it seems to me, the point of life is whatever you make of it. I'm getting the impression that the point of your life is to experience as much pleasure as possible, i.e.: hedonism. This is a perfectly valid approach to one's life, but I wouldn't assume that others are getting less enjoyment out of their existence simply because they choose to impose constraints on the pleasures they pursue.
Metformin is a pretty serious drug and that is a high dose. It's one thing to use it for off-label use like PCOS, but I would be very cautious for a more nebulous use.
Metformin is fairly safe and toxicity doesn't occur until you reach doses that are many, many times higher than therapeutic doses [1] [2]. Not a doctor, not your doctor, talk to your GP before starting such a regimen (especially for healthy kidney and liver function). My prescription was a 3 minute convo after my annual physical ("its safe, my kidneys and liver are working, I want to live longer [3] [4], and I will sign a waiver I won't hold you liable if necessary"), and I would've just ordered it online if my doctor said no.

[1] https://care.diabetesjournals.org/content/35/4/731

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934269/

[3] https://www.ncbi.nlm.nih.gov/pubmed/25041462

[4] https://clinicaltrials.gov/ct2/show/NCT02432287

Did you have diarrhea when you started Metformin?
None. Some people do, it is a documented side effect.
Not just diarrhea but this horrible greasy concoction that required a shower...

Metformin could be sold as an ultra laxative for some folks...

What does metformin do for therapeutic purposes? wiki doesn't allude to much besides diabetes treatment.

https://en.wikipedia.org/wiki/Metformin

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Basically, the TLDR is that it makes the insulin your body produces work better.

The nice thing about it is that it can't drive your blood sugar low.

> Metformin is a pretty serious drug and that is a high dose.

According to a former endocrinologist of mine, 1000mg daily is the lowest effective dose. 500mg pills are the lowest dose available. What is your source for 1000mg being a "high dose"?

For diabetes or PCOS, sure.

What is the effective dose for general life extension?

Sugar in your coffee ain't gonna make you overweight.

Have real sugar, don't take sketchy drugs, live a generally healthy balanced life.

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If you reduce the amount of sweetener slowly, you will likely eventually get used to just drinking coffee black.

I've suggested this to 5 different people over the course of my life and it worked for 100% of them.

Feel free to ignore this suggestion, but I can't see any downsides ;-) Worst case scenario is you're still drinking the same amount of sweetener a few months from now

It is. Everyone knows that the real solution to all these health problems is “eat right and exercise”, but there’s clearly a huge market of people looking for a “magic pill” to solve their problems instead of doing that.

Snake oil has been around as long as humanity itself, so you might as well do some studies on it since so many people will be using it.

That is true for so many diseases, like anything related to obesity, diet, exercise and smoking. Doctors are too ready to prescribe pills instead of an exercise regimen or diet.

I wonder if doing studies on specific exercise regimes and diets would give doctors more confidence to prescribe them as cures. The problem is there is so much less money to be made for a certain industry.

There's that, and there's also compliance - if your doctor tells you you should become a vegan ultramarathoner, chances are you will probably not comply; if they tell you to take two pills every morning, you may still not, but the chances are at least better (even if the improvement is also less significant).
Doctors (in the US) run a business, and you’re not likely to get repeat customers if you tell them they need to lose weight, because they will take it personally and go find someone else who will prescribe a magic pill. Many doctors might mention it offhand, but if they really harp on it they will lose the patient to someone else.

It’s not a good situation, but it is the reality.

Exercise part of that solution is much more expensive than almost any pills (if they'd exist). 2h exercise a week at Valley tech salaries ($150/h) might cost you ~$15000 in time per year.

Another way to look at it is in 40 years it will consume two entire years of working full-time.

And that does not include cost to go to gym like transportation time, change of clothes, etc

this is all positively ridiculous.

Do you calculate all your other hobbies like this? You probably have "spent" millions playing video games

This one easy trick will save you $150! Just stay up an hour after bedtime ;)

I got in the habit of doing this kind of calculation early in my career before realising it is a) pointless unless someone will actually pay you that money if you instead do work, and b) still not a healthy way to think anyway in many cases where a) is true, due to life's necessities.

It might be "cheaper" to pay a kid to mow the lawn but sometimes I find it relaxing.

Perhaps to some people it might be ridiculous.

This, however, is not applicable to hobbies. Hobbies are what one tries to save time for. If for you gym is a hobby, you should not be doing the above calculation.

There are so many things wrong with this perspective I’m not sure where to start. Overall it sounds very much like the climate change deniers’ arguments — who cares if we all die, as long as we make some money beforehand.

You can not compare Si Valley salaries to anything, since they are irrelevant. The salary may be high, but so is the cost of living there, so it’s basically a wash. And Si Valley is not the center of the world, so comparisons to the relatively few people who live there are meaningless.

Who cares if it consumes 2 years working time if you die 10 years earlier than you would have. Also exercise gives you many health benefits, including cognitive function, so you will be more healthy and more productive when you actually are working.

Cost to go to the gym?! You can exercise at literally 0 cost. Do some push ups, go outside for a run, etc.

> Who cares if it consumes 2 years working time if you die 10 years earlier than you would have.

Your 10 years number is significantly overblown. First result in Google is:

> they found that those who did 75 minutes of moderate-intensity activity weekly lived 1.8 years longer, on average, compared with people who did no physical activity

If you believe that, it puts it into 1.25 (no exercise) vs 1.8 years, which still does not include any preparations.

Death is an awful yardstick to measure anything other than truly fatal conditions. Exercise can be the difference between spending 50 years with major health problems, joint and back pain, diabetes, etc vs spending them pain free and being able to enjoy life.
Exercise can be done without gym or special equipment. Healthy food does not mean Vegan-gluten free-paleo-ethically grown, it means balanced eating and minimally processed, the only extra thing it costs is convenience.
thanks for the article. I am cutting down on all sugar completely. Already started feeling better and lost some weight just by cutting the sugar.
This is the "let's hang a chlorine on some sugar" sweetener right? It always struck me as implausible that it would be biologically inery.
Yes, sucralose is chlorinated sucrose (table sugar).

If the structural formula looks like a pesticide it might be better to not ingest it.

> If the structural formula looks like a pesticide it might be better to not ingest it.

When I first saw discussion of sucralose that was my response-- 'wtf, that looks like a pesticide'.

Then I found out how it was discovered: A chemist misheard 'test the compound' as 'taste the compound'. ( http://www.laleva.org/eng/2006/12/the_history_of_splenda_the... )

But the fact that it obviously looks like probably-bad-news is probably good news for its safety: It has been very widely tested, including by a lot of people who were expecting it to be poisonous. And in spite of all that testing and deployment to the public in enormous quantities, there is little to suggest that it isn't safe. If it does turn out to have negative effects, they can't be that significant or serious or we would have noticed by now.

The negative health effects of sugar are well established. To the extent that sucralose is displacing sugar it's almost certainly a net benefit.

The natural question that comes to mind is what ratio mixture of a sugar and an artificial sweetener can be used without encountering the negative metabolic effects. Being able to reduce sugar and calorie intake using such a mixture would still be better than nothing.
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Allulose is an interesting sweetener that has the same molecular formula as fructose, and IMO tastes much more similar to table sugar than other sweeteners.

It has been shown to lower glycemic and insulin response when taken with other carbs https://www.ncbi.nlm.nih.gov/pubmed/19155592

I'm guessing because of the molecular similarity I've found it to have similar browning as sugar when cooking.

A few downsides--it has a cooling sensation depending on what I use it to sweeten. Also if I consume too much it can cause bloating (a downside of not being absorbed like sugar is). In general it doesn't look like it's as well researched as other sweeteners, so it's hard to tell if there are more subtle/long term downsides.

More here: https://en.wikipedia.org/wiki/Psicose

I've always thought that LCS were far less harmful than sugar because your consuming 10 times less of the substance than a taste equivalent amount of sugar. You'll notice that when you consume a combination of Sucralose and maltodextrix, there's 10 times less of it (but they make 1tsp taste equivalnet to 1 tsp of sugar), but density is 10 times less.

If this isn't true, then it blows my mind!

This isn't particularly sound logic - that a substance is automatically less harmful because you may consume less of it for a similar effect?
They are so chemically different that that doesn't really hold. 500mg of KCN is certainly worse for you than 5g of sugar, despite being 10x less.
Why would the amount of maltodextrin in granulated sucralose products that combine maltodextrin with sucralose have anything to do with the question of whether sucralose is bad for you?
Because there's 10 times less of it there.

Hypothetically, if maltodextrin was equally bad for you as sugar, then you'd consume 10 times less harm.

When these sorts of studies first came out, I came to grips with the notion that honesty was the best policy.

Lying to your body about what it’s eating seems not to work out. You need a healthier relationship with sweets, not sugar.

Yup, it always makes me think "TANSTAAFL". I used to be a big soda drinker in my teens; pretty much cut it out as an adult but those calories were probably replaced with beer.

As someone who meal tracks and exercises regularly, I definitely generally feel (calories in)-(calories out) is most of what matters, BUT, once you start doing that, there just isn't much room for junk. You can't really exercise your way out of a tub of ice cream a day. The more you work out, the more (good) fuel you're gonna need, so there's only so much wiggle room for junk.

Sadly, when I do have my soda-or-two a month, because I DO calorie count, I've finally given in and started having something like Coke Zero, but I should probably stop lying to myself, just have the real thing, and track it for the calories it has :)

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Would it just be better for people who are getting too much sugar to eat less of it?
What does the quantity of food consumed have to do with this?
Strange study. Maltodextrin is basically pure glucose, it hits the bloodstream right away and in a very high concentration. This is why it is used in "gainers" bodybuilders take after hard workouts, to trigger insulin response and replenish muscle glycogen.

Sucrose has to go through the liver first, so its release and concentration will necessarily be much lower. Not as low as for fructose, but lower than for maltodextrin. Its half life will be longer as well.

The point is, the two sugars aren't even using the same metabolic pathways, and yet they compare them as interchangeable. WTF?

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