
Study: Artificial sweeteners toxic to digestive gut bacteria - shawn
https://www.cnbc.com/2018/10/03/artificial-sweeteners-are-toxic-to-digestive-gut-bacteria-study.html
======
biomcgary
The underlying research article
([https://www.mdpi.com/1420-3049/23/10/2454](https://www.mdpi.com/1420-3049/23/10/2454))
is set up as a "no-fail" experiment since it infers toxicity with the
slightest change (inhibition or induction) in a very sensitive reporter
(luciferase). They are NOT measuring change in growth rate of the bacterial
cells, the traditional measure of toxicity (aka IC, or inhibitory
concentration). The study has positive and negative controls, but this assay
is poorly controlled relative to how it is being interpreted (impact of
artificial sweeteners on human gut microbiome).

The only way to accurately calibrate this novel assay for relevance to human
health is to expose the bacteria to a wide range of natural foods (e.g.,
avocado, spinach, berries, honey, etc) and show that it does not return a
positive result. If nearly everything is toxic, the assay is not useful.
However, if most natural foods have no toxicity signal, then the assay has
genuine value.

~~~
mohaine
I've always found any of these studies that treat artificial sweeteners as a
single group very suspect.

1) The only thing the different types of Artificial Sweeteners have in common
is a high sweetness value per volume (2k-4k time more sweet than sugar is
common). Other than that they are different chemicals so it seems strange to
treat them a single group. Sure a few of them might have issues but it seems
silly to say they all have the same single issue. Really a red flag for who
funded the study.

2) Due to the very high sweetness levels compared to sugar, even if the
artificial sweetener is many times worse than sugar per volume, it is still
safer due to only 1/2k being actually being used.

~~~
Bartweiss
> _treat artificial sweeteners as a single group_

In defense of an otherwise-poor study, it didn't do this. Six of the most
common artificial sweeteners were tested on the bacterial assay and their
results reported and discussed separately. Another sequence of assays was run
on a panel of sports supplements with varying sweeteners. It looks to me like
the only reason for grouping these chemicals was practical - they have
interchangeable dietary uses, so it's helpful to observe their varying
responses on a single test.

It'd be a pretty interesting study, except that the assay's quality and
sensitivity seem hugely in doubt.

~~~
bunderbunder
Doubling down on that point a bit more -

I think that, assuming the study is high quality, one that looks at all the
popular artificial sweeteners together is probably more valuable from a
"practical application" perspective, because it allows you to make more of an
apples-to-apples comparison among the individual sweeteners.

If all you've got is bunch of isolated studies that only look at one of them
at a time, you'll always have some room for doubt about whether a difference
in outcome reflects the sweetener being tested, or some difference in the
experimental protocol.

------
cheeko1234
Top comment at r/science:

Ordinary table salt and most other essential non-organic mineral naturally
found in healthy foods, are toxic in increasing doses to bacteria. As a
biochemist I'd be willing to bet that those necessary minerals in the human
diet would stress the hell out of these bacteria in increasing doses also. The
bacteria in this paper do NOT show growth inhibition with these artificial
sweeteners in the doses used.

It's a pretty huge jump in scientific presumption - from a change in
fluorescence in a contrived sub-inhibitory bacterial "stress" assay, to the
authors statement of "we may speculate that the response observed in our study
may be relevant to gut microbiome and thus may influence human health".
(statements in italics not tested by authors)

So doubt their basic premise has any validity.

[https://www.reddit.com/r/science/comments/9ki9nw/scientists_...](https://www.reddit.com/r/science/comments/9ki9nw/scientists_report_many_artificial_sweeteners/)

Not only that, they were only using a fluorescing E. coli as a proxy for the
incredibly diverse gut microbiota. For it to have any real bearing on human
health, they'd need to do at least an animal model study and show a difference
in 16s rRNA quantitation and/or sequencing for relative abundances of
different species. But I sympathize with the need to make your study sound
significant and worth doing....

------
qwerty456127
The article doesn't say which sweeteners did they study and this is a very bad
style. Fortunately it links to an article on EurekAlert which in its turn
links to the actual scientific paper (doi.org/10.3390/molecules23102454). It
says aspartame, sucralose, saccharine, neotame, advantame and acesulfame
potassium-k (ace-k) (BTW at least saccharine and ace-k are already known to be
carcinogenic AFAIK) were tested against Escherichia Coli (I would rather be
interested in testing them against Lactobacillaceae).

Lactulose is a great prebiotic (not widely known infortunately) very good for
gut bacteria (AFAIK), has geroprotective properties, is a mild osmotic
laxative, has zero calories, doesn't affect blood sugar/insulin and tastes
great. I use it instead of maple syrup. As far as I also know erythritol
(looks, feels and cooks almost exactly like sugar) and palatinose (same, but
has calories yet doesn't kick insulin and doesn't feed mouth bacteria so is
safe for teeth) are good for gut bacteria too. We could also mention inulin
(which is a well-known prebiotic very beneficial for gut microbiome) but it's
sweetness is weaker.

~~~
logfromblammo
Paranoid mistrust, cancer fears, and fart-driven explosive diarrhea had
already winnowed my list of non-sucrose sweeteners down to just erythritol,
pure stevia powder, and very small amounts of xylitol.

I'll have to look into lactulose and palatinose.... And it looks like
lactulose is out for the diarrhea reason, and isomaltulose--Palatinose is a
trademarked name for it--looks practically identical to slow-motion sucrose,
including caloric content. It has a lower glycemic index, but is half as sweet
as sucrose, so you may end up consuming more calories for the same amount of
sweetness.

Erythritol is not good for gut bacteria. It is 90% absorbed before reaching
the colon, and excreted mostly intact in urine and feces, and the early
absorption is why it doesn't have the diarrheal effect common to most sugar
alcohols. Sweeteners that are neither absorbed nor digested draw water out of
the digestive tract as they pass. Those that can be fermented by colon
bacteria also tend to produce gases, that help push the water out. Xylitol is
not fermentable, so the diarrhea you might get won't be quite so bad.

I think I'll stick with a mix of erthyritol and stevia, with proportions
titrated such that equal-volume measures of erythritol/stevia and sucrose
crystals have roughly equivalent sweetness. The flavor profile isn't quite
right, but it's good enough for me until something better comes along.

(edit) I'll also add that it seems to work best in foods where other flavors
can dominate. While you can sort of taste it as not being real sugar in
lemonade, in sugar-free fudge, all you can taste is the sweetness. But it also
forms crystals during cooling, and I haven't quite worked that out yet.
Gritty/crunchy fudge is not exactly ideal.

~~~
jfhufl
I've found that stevia sweeteners with inulin (not insulin) seen to be
beneficial for my gut bacteria. Actually seems to help with "loose days".

Sweetleaf is generally what I use.

~~~
qwerty456127
Inulin may "help with loose days" much more than you probably think. It may
actually help to systematically decrease your appetite and insulin resistance,
decrease ghrelin (the "hunger hormone") and increase leptin (the "fullness
hormone") if you eat it every day. I can recommend Dr. Raphael Kellman's "The
microbiome diet" book for more info, it is easy and exciting to read and has a
fair amount references to scientific research in it, it may happen that you
will never have to worry about calories again after you read it.

------
raisedbyninjas
There are only 12 milligrams of sucralose in a packet of Splenda. So the toxic
levels found in mice had the same concentration as an 8 oz. cup of coffee with
16 packets of Splenda.

~~~
jaxtellerSoA
>an 8 oz. cup of coffee with 16 packets of Splenda.

I have literally seen people do such things at Dunkin Donuts. "Yeah can I get
a medium coffee with extra cream and 20 sugars." You WUT M8?

~~~
emodendroket
At a certain point you have to admit to yourself that you just don't like
coffee.

~~~
SketchySeaBeast
With that much sugar I'm not sure if it's the flavour or texture you don't
like.

------
KingMachiavelli
The article is a bit confusing in that they refer to two separate studies.
Both of the studies are open access

(Neotame)
[https://www.mdpi.com/1420-3049/23/2/367](https://www.mdpi.com/1420-3049/23/2/367)
(6 sweeteners)
[https://www.mdpi.com/1420-3049/23/10/2454](https://www.mdpi.com/1420-3049/23/10/2454)

Also there seems to be a typo in the article:

> ...the bacteria found in the digestive system became toxic.

I don't think they mean the bacteria themselves became toxic.

------
CannisterFlux
Seems like everything has artificial sweeteners nowadays. It's a trend that I
noticed only in the last couple of years. And not just fizzy drinks like
Sprite or Pepsi - which have sugar _and_ sweetener! - but breakfast cereals,
yoghurts, ketchup-like sauces... all have "no added sugar" on the package, you
dig a bit deeper and they are full of sweeteners.

Chewing gum and other "healthy sweet" products like that have used sweetener
for years, and have always had a warning not to take too much, or it'll give
you the shits. Clearly bad for your gut or you wouldn't be getting these side
effects. Yet here we are, with sweeteners everywhere and getting more
pervasive.

I just try to avoid sugar and sweeteners as much as possible. Seems like half
the things I add in "My Fitness Pal" have a little orange warning about
something :(

~~~
DanBC
> Clearly bad for your gut or you wouldn't be getting these side effects.

That's not how that works. Ifyou eat too much fruit the sugar in that can
cause a laxative effect,and the mecahnism is the same as with suga alcohols.
The undigested sugar causes osmosis, which floods the gut with water, which
causes diarrhea.

~~~
atomical
There have been studies done where patients were given lots of fruit and it
did not cause a laxative effect.

[https://nutritionfacts.org/2017/02/23/can-you-eat-too-
much-f...](https://nutritionfacts.org/2017/02/23/can-you-eat-too-much-fruit/)

> Seventeen people were made to eat 20 servings a day of fruit. Despite the
> extraordinarily high fructose content of this diet, presumably about 200
> g/d—eight cans of soda worth, the investigators reported no adverse effects
> (and possible benefit actually) for body weight, blood pressure, and insulin
> and lipid levels after three to six months.

~~~
hexane360
That article says nothing about a laxative effect.

~~~
atomical
Exactly.

~~~
hexane360
You failed to provide evidence that fruit exhibits no laxative effect. That
study didn't report a laxative effect because it wasn't testing for a laxative
effect.

~~~
atomical
It would have been reported as an adverse effect and it wasn't.

------
pieter_mj
Currently a perfect diabetes, obesitas (and also cancer & alzheimer's) storm
is brewing.

My gut instinct (pun intended) tells me it mainly has dietary causes which are
not limited to increased portions alone.

~~~
nervousvarun
Processed foods + sedentary lifestyles = perfect storm.

Pretty obvious "something" happened in the 70s and we've been on this ride
ever since:
[https://nchspressroom.files.wordpress.com/2010/01/obesity.gi...](https://nchspressroom.files.wordpress.com/2010/01/obesity.gif)

~~~
vezycash
If someone is sick, they'll become slow. All they'll want to do is lie down
some place quiet.

Watch kids, healthy kids. After a meal, all they want to do is run, talk, jump
- move. Sitting still is the last thing they want to do.

My point is perhaps, sedentary behavior is caused by something, a symptom
outside the control of those afflicted by it.

Here are some culprits we could explore:

Schooling: Being trained, forced to sit in a spot for hours could train people
to be sedentary.

Processed food: Maybe its doing something to the body. Like how zombie ants
are controlled by fungi.

Aging process: All animals become less active with age... Even snails.

Environment: Tech makes it harder to be active physically. A tv remote, car,
internet for shopping...

Poverty: There's a proven link between experiencing poverty at a young age and
inability to control food intake, and spend responsibly.

Genes: People used to bulk up for winter hunger. Now there's food all year
round. But the lizard brain is still in control.

There might be more reasons why people binge eat, and remain sedentary such as
processed water, poor air quality, domestication (The more Wolf gene a Dog
has, the more active it is)...

~~~
datavirtue
Refined oils, fat, and animal protien cause arterial hardening immediately,
lasting for several hours. Keep ingesting and you end up with heart
disease....arteries filled with plaque restricting blood flow, raspiration,
mental function. Ingesting refined sugar and flour causes an insulin spike
(make fat out of carbs!) that lasts for hours causing a crash and repeated
cravings for...more carbs. This leads to diabetes. Cancer needs sugar and
animal protien to live.

Check out China study.

~~~
haisch
Fat is slept on macronutrient because of the misguided idea that increased fat
= increased cholesterol in arteries. Vitamin K2 is an important vitamin that
isn't metabolized well from foods containing K1 (vegetables). Animal sources
and natto (fermented soy beans) are the best sources of it. It has been shown
to help with heart disease, cancer and bone health.

The interesting thing with animal protein is that no study has shown a dose
dependent increase in cancer when consuming more of it. Chronic inflammation
from gluten, processed foods, pesticides, refined carbs, and refined sugars
are the biggest culprits in dietary endorsed cancer.

~~~
datavirtue
So you are denying that endothelial dysfunction and it's triggers exist?
Interesting.

~~~
haisch
Its triggers are high insulin, high fasting blood sugar, high triglycerides
and low ldl. These are all caused by the food types I listed. High fat low
carb diets have been shown to reduce all of these symptoms.

------
ackfoo
I am concerned by the absence of a dose-response until above a threshold
concentration for all substances tested. Perhaps osmotic effects,
displacement, and chemical competition for receptors, all of which may be in-
vitro effects, may explain the curves. Is the threshold relevant to in-vivo
concentrations? No idea.

The reason toxicity is expressed as an LD50 is to account for the dose-
response of toxins. If toxins behaved as purported in this experiment, we
could use a simple concentration number instead: no effect, no effect, no
effect, dead.

Also, it looks like all the substances that showed toxic induction did so
around the same concentration. Very suspicious for chemically disparate
substances with, presumably, different mechanisms of action.

“How can we all have died at the same time? ...(thinks)...The salmon mousse!”

------
nikkwong
I was big on artificial sweeteners (I refuse to eat any sugar), mainly
erythritol and monkfruit, but some science(1) says that just their taste
profile can trick your body into thinking it's consuming a real sugar with the
associated glucose/insulin response and this could be one reason as to why
non-nutritive sweeteners can throw your blood and insulin response profiles
out of whack, which may be a reason as to why individuals who consume
artificial sweeteners suffer the same maladies as those who consume high
levels of sugar.

If the science on this issue becomes conclusively affirmative, then it's sort
of the nail in the coffin for artificial sweeteners, because it doesn't matter
what the compositional makeup of the sweetener is, it's our own bodies own
responses to the taste/smell that are giving us the ill effects.

I would definitely like to be dissuaded as to believing this is not the case,
though, as it's caused my to ignore my sweet tooth for far too long! :)

For those who are interested in and/or consume artificial sweeteners, I think
this link is definitely worth a read:

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661066/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661066/)

------
andy_ppp
It would be interesting to see some kind of health warning with stats or
articles, including replication, funding sources, invitro/animal/human studies
etc.

I just cannot trust even the most basic science announcements on mainstream
media as things stand. It is simply more important that it generates clicks
than it advanced people’s understanding these days.

------
oxymoran
Perhaps this an avenue towards a new type of antibiotic?

------
thegabez
Anecdotally I've noticed when I chew large amounts of artificially sweetened
gum (mentos pure fresh) throughout the day, I will have restless legs
throughout the night.

------
dual_basis
It's pretty clear to me that there is significant bias in the premise. Why,
specifically, should it be artificial sweeteners that are toxic to gut
bacteria? Irony is not a scientific motivation, it is a journalistic
motivation. What makes artificial sweeteners more likely to be toxic to gut
bacteria than, say, food coloring, preservatives, or (dare I say it) natural
herbs and spices?

------
dayvid
You can thank former Secretary of State Donald Rumsfeld for allowing Aspartame
to remain FDA approved despite scientific research concerns:

[https://tonic.vice.com/en_us/article/nzpbkx/the-story-of-
how...](https://tonic.vice.com/en_us/article/nzpbkx/the-story-of-how-fake-
sugar-got-approved-is-scary-as-hell)

~~~
spadros
Meh, this study is misleading. They didn't test if any other foods had the
same effect. So sure, sweeteners might have a detrimental effect by this
biomarker. But they didn't check if anything we'd consider healthy, like
broccoli or onions, have similar effects.

This is like saying "smoking increases your change of a heart attack 10X after
one puff!" without noting "...but having sex increases it 7X and drinking a
can of coke increases it 5X".

------
apeace
Off-topic, here is one of my favorite HN comments ever, about artificial
sweeteners:
[https://news.ycombinator.com/item?id=9440566](https://news.ycombinator.com/item?id=9440566)

------
milin
Reading this while enjoying my diet coke was a bad idea.

~~~
jwbwater
I feel you. I was drinking a coke at dinner with a friend who started talking
about how sugar suppresses the immune system. The coke just didn't taste the
same after that.

------
dvfjsdhgfv
It looks like the study confirms what we already knew. It would be more
interesting to see what happens with what are considered more healthy
alternatives, such as xylitol or erythritol. They seem to be "mostly fine",
but more research would be very beneficial given that people use them more and
more.

------
wattengard
I'm not a mouse...

~~~
vezycash
>I'm not a mouse...

Expanded: Animal studies are just a start. Human trials might get opposite
results.

E.g. The drug Indocid or Indocin is safe for human consumption but kills rats.
It's a cheap rat killer.

If rats were tested first, we'd assume they'll kill humans. The reverse
applies as well.

------
emodendroket
Putting that aside, they also give you horrible gas.

------
clumsysmurf
Anyone know how gut bacteria respond to Stevia?

------
amelius
When will we have artificial fat?

~~~
Bartweiss
Oh man, that is a tough order.

Sugar has the convenient trait of being essentially a flavor, so all that's
needed is to trick chemical receptors on the tongue with something that's
nontoxic and either not bioavailable or very high intensity relative to
sucrose. Fat ends up affecting flavor, mouthfeel, and food traits (e.g. water
retention, bulk) - and a lot of those roles are inherently tied to fat volume.

Safe, bio-unavailable fats already exist, more or less, in the form of fatty
alcohols. They can cause minor irritation to the liver, but nonlinear long-
chain fatty acids are safe enough that we already use them in food as
emulsifiers. Wax esters, which bind fatty alcohols to fatty acids (i.e. normal
fats), are also poorly digested and extremely fat-like. Escolar and oilfish
are notable as fatty fish with wax esters making up almost all of the fat.

Unfortunately, that 'volume' issue now comes home to roost. Wax esters in low
doses (e.g. orange roughy) are fine, but in high doses (e.g. escolar), they
tend to cause stomach pain and bowel issues - not because they're toxic, but
because they simply aren't digested. Other replacement fats like Olestra (once
FDA approved as a fat substitute) have the same problem: they simply come out
in the same form they went in.

To replace a significant portion of our "fat experience" with artificial fat
means we need something which is similar in the mouth, low calorie and
cholesterol, but also digestible. The best options we've found are either
variant fats with lower absorption and calorie density, or other-macronutrient
substances which serve only some of the same roles, like pectin or whey.
Those, again, can lower cholesterol but can't do much better than half the
calorie density of fat.

I'm not sure what artificial fat on the level of artificial sugar would mean.
It would, I suppose, have to be something which is digested sufficiently to
excrete without deriving energy or other components like cholesterol. And in
an Algernon Argument sort of way, we probably shouldn't expect to find the
body digesting very many compounds it derives no benefit from, so "somewhat
better" is probably all we can hope for.

------
WhiteSage
The title is slightly misleading. The study is only about neotame, and not
artificial sweeteners in general.

EDIT: Nevermind, only one article was linked. Thank you for linking the rest
below.

~~~
ceejayoz
Huh? The second paragraph says "six common artificial sweeteners", and the
third says:

> Researchers from Ben-Gurion University of the Negev in Israel and Nanyang
> Technological University in Singapore tested the toxicity of aspartame,
> sucralose, saccharine, neotame, advantame, and acesulfame potassium-k. They
> observed that when exposed to only 1 milligram per milliliter of the
> artificial sweeteners, the bacteria found in the digestive system became
> toxic.

~~~
contingencies
It links to two studies.

Neotame (2018-02-09) @
[https://www.mdpi.com/1420-3049/23/2/367](https://www.mdpi.com/1420-3049/23/2/367)

Sweeteners (2018-09-25) @
[https://www.mdpi.com/1420-3049/23/10/2454](https://www.mdpi.com/1420-3049/23/10/2454)

