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Artificial sweeteners linked to glucose intolerance (newscientist.com)
412 points by bensedat on Sept 17, 2014 | hide | past | web | favorite | 180 comments



I like how all the people who benefit from artificial sweeteners are refuting something which the study doesn't claim. For example:

  "The International Sweeteners Association (ISA) says it strongly
   refutes the claims made in the study: 'There is a broad body of
   scientific evidence which clearly demonstrates that low-calorie
   sweeteners are not associated with an increased risk of obesity
   and diabetes as they do not have an effect on appetite, blood
   glucose levels or weight gain.'"
It's true that artificial sweeteners have no immediate effect on appetite, blood glucose levels, nor weight gain. None of these are claims made by the study. Everyone is refuting the immediate effects of artificial sweeteners. The study claims that after consuming artificial sweeteners, if you then consume something naturally sweet, the prior consumption of an artificial sweetener alters your glucose tolerance levels.

It's the equivalent of saying that removing all the trees from around rivers has no effect on fish population because clearly fish don't live in trees. But it's the secondary effects of this which such a statement ignores: the increase in soil erosion impacting water quality, change in water temperature due to having more direct sunlight, and so on.

Also:

  "'Decades of clinical research shows that low-calorie sweeteners
   have been found to aid weight-control when part of an overall
   healthy diet, and assist with diabetes management,' says Gavin
   Partington of the British Soft Drinks Association."
This has little meaning without having a reference point to compare the results to. If the study is correct, take one group of people who use diet soft drinks with an overall healthy diet and compare it to another group of people who consume the same overall healthy diet but drink water instead of diet soft drinks, and the group that drinks water should have a better glucose tolerance response than the diet soft drink group.


You just hit one of my pet peeves. "...when part of a healthy diet". Only cigarettes fail that test as far as I can tell.

Eating deep-fried Twinkies and a 32oz Mountain Dew is not bad for you, when done as part of an overall healthy diet.


Right, by definition, consuming any food is not bad for you, when done as part of an overall healthy diet -- any overall diet in which the food was bad for you would not, ipso facto, be a healthy diet when that food was included.

The claim would only begin to be meaningful if instead of "when part of a healthy diet" it was "when included in an otherwise healthy diet".


Not necessarily. You could smoke one cigarette now, and you would be less healthy. But if you never smoked again, you would not have transitioned to unhealthy

The first term is relative, the second absolute. If the diet is overall healthy, it's possible it has some bad food. It's less healthy than if it didn't, but not unhealthy.


Which just made me wonder if it's possible to train a hidden markov model for detecting that. Trigger a flag that says "wowzers, now you're in unhealthy state territory". Otherwise it's real hard to tell if occasional engagements with unhealthy behaviors are having an impact on health overall. I imagine we'll get to the point of being able to do this sort of thing in about five years.


"In about 5 years" is often code for, "It is really cool, and it seems feasible, but I have no idea how difficult it really is."

Also, we have the basic capability for this now. Regular blood testing, etc. Get a physical. Get blood work every 3-6 months. Its just basic stats for your body. I do this. To me it is like checking the oil levels in a car. Why would you not collect this type of data for your body, which is arguably one of the most important "possessions" a person can own?


What's included in the blood testing?

I'm in Canada, and the idea of routine blood testing for young people (I'm 29) doesn't seem to have caught on.


That's because our medical system isn't for-profit, so we only get blood tests when they're medically necessary and not just for convenience.


> Which just made me wonder if it's possible to train a hidden markov model for detecting that. Trigger a flag that says "wowzers, now you're in unhealthy state territory".

Unlikely, because how much "less healthy" becomes "unhealthy" is an arbitrary subjective point rather than being something fixed and objective (and because the degree of health impact of various decisions varies widely based on individual factors that aren't all known with any kind of precision, so, even with a fixed objective of 'healthy state', the point at which the average person would reach it and the point at which you reach it may be not at all similar.)

> I imagine we'll get to the point of being able to do this sort of thing in about five years.

I imagine we'll not be meaningfully closer to being able to do this than we are now in about five years. (OTOH, I wouldn't be surprised to see someone marketing something that purports to do this in that time.)


I'm not sure I understand. Are you implying there is evidence showing that smoking one cigarette causes you to be permanently unhealthy?


His claim is the opposite of that.

Smoking one cigarette does not make you unhealthy. Smoking one cigarette does make you slightly less healthy.

Think of it as death by a thousand cuts. Lopping off the tip of my finger won't likely kill me, though it does hurt. Keep lopping though, and eventually I am less and less healthy, until at some point, I am dead.


That depends on which camp you plant your flag. Dr. Ron Rosedale would probably have something to say about that insofar as any overintake of dietary glucose is a bad thing. We simply don't need even moderate amounts of it in our diets, especially for primarily sedentary lifestyles.

His position is that even a small degree of glycosylation contributes to accelerated aging, albeit the degree of which determines how chronic and insidious that damage will actually be.

I tend to agree with his take on the matter. Objectively speaking, especially if you subscribe to the insulin hypothesis of adiposity, there are several "unhealthy" biomarkers that occur as a result of intaking deep-fried twinkies and mountain dew — irrespective of peri-indiscretion nutrition.


"Part of this nutritious breakfast". Actual nutritious breakfast pictured surrounding nutritionally vapid sugar-coated ground corn husk "cereal" thats probably not even properly considered a food.


Mountain Dew like most soda is bad for you. If nothing else it's bad for your teeth and the acid harms your throat.

Now, it's not all that harmful and if your starving the calories are useful but starvation is not a healthy diet.


It seems like we have no idea whether soda is bad for you, since people who consume soda live long lives. As far as I know, their throats are also fine. It's not even necessarily a fact that sugar harms teeth as long as someone is brushing each day.


Soda is not in contact with your teeth for long enough to cause any damage, the acidity in basically all fruit would be just as bad by any meaningful measure of harm.

Carbohydrate snacks like crisps etc are much worse.


People eat fruit fairly quickly. But, many people sip soda for hours a day which is a vary different situation. Not only do they get acid but the constant low levels of sugar promote significant bacterial growth.

Also, unlike fruit soda has water and sugar, but no nutrients what so ever.

http://www.wda.org/your-oral-health/sip-all-day

http://health.usnews.com/health-news/articles/2012/06/11/5-m...


So, in your wold view death is the only measure of harm? Because, most people also assume pain such as that caused by a cavity's is also bad. And, historically people had far fewer cavity's before refined sugar became part of everyone's diet. Modern dentistry can mitigate that significantly, but it's not a panacea.

edit: The studies linked are interesting, but I think this quote stands on it's own.

"Soft drinks have emerged as one of the most significant dietary sources of tooth decay, affecting people of all ages." http://www.colgate.com/app/CP/US/EN/OC/Information/Articles/...

Harnack L, Stang J, Story M. Soft drink consumption among US children and adolescents: Nutritional consequences. Journal of the American Dietetic Association 1999;99:436-444.

Brimacombe C. The effect of extensive consumption of soda pop on the permanent dentition: A case report. Northwest Dentistry 2001;80:23-25.


Well to be fair you could smoke a cigar infrequently enough to have no defineable effect on your health and the act of sitting down and relaxing quietly for a half hour for a good cigar is likely to be beneficial to your health.

So given enough twisting of the facts you can argue anything is good in moderation. I mean infrequent heroin use given the proper precautions and clean product could be part of a "healthy lifestyle", but its still shooting heroin.

Part of a healthy diet should mean you can do it at least daily not once a month.


Well, except for the mouth cancer...


Except alcohol does the same and people consume that a lot more frequently and doctors advocate moderated use.


I think they say that because they don't want people to think there is just one thing in their diet they have to change.


Pet peeves, falling for anti-cigarette propaganda.

In moderation with a healthy diet they are as fine as Twinkies and 32oz Mountain Dew.

Like Mountain Dew they are abused so perhaps abstinence is best, depends on personal will power.


> It's true that artificial sweeteners have no immediate effect on appetite

Yes, but the quote you give doesn't mention immediate effects in particular. And to the contrary, they mention things like obesity and diabetes which are not immediate effects.

To me, it sounds like they are not saying what you say they are.


The mentions of obesity and diabetes are written as direct causal relationships. To rearrange their quote without changing the meaning:

  "because low-calorie sweeteners do not have an effect on
   appetite, blood glucose levels or weight gain, they are not
   associated with an increased risk of obesity and diabetes"
Essentially, this says "if (no effect) then (no risk caused by effects)". As long as it's true that low-calorie sweeteners themselves don't have an effect on appetite, blood glucose levels, or weight gain then they're free to make the above implication. However, the statement is only a partial truth and has no bearing on the study under discussion.

If they wanted to directly respond to the study, they wouldn't keep quoting old studies which didn't attempt to investigate the results of the new research; they should instead say that they will study it and attempt to replicate the results, then issue a statement once they've understood the full implications. Of course, that wouldn't be a strong defensive statement of their vested interest so they of course can't say that.


They are saying what they always say whenever anyone questions the safety/healthiness of their products. Their response is the equivalent of a form letter. It's akin to the statements that the tobacco companies made before congress, well-rehearsed and carefully worded to be deceiving. It's why they always seem to not address the specifics of what the scientific study actually found...because they intentionally aren't addressing it.

It's part of their larger playbook for continuing to poison the US population. That same playbook also has strategies for when regulation is proposed (increase campaign contributions, stress individual freedom to choose and responsibility and begin self-imposed reforms) and they've been doing it ever since the McGovern report suggested that our food might be harmful to our health. Thus far, they've gotten away with it every single time.


For each quote, I wondered whether the journalist selected the worst part to make them look arrogant/ignorant. Later in the article there are more reasonable answers they could have used, saying there has been research (and funds?) allocated to this topic and they had found nothing, saying that there are several levels of peer review until a scientific study acquires the credit of trust, that further research and counter-studies are necessary before anything is confirmed, that based on the current knowledge there is nothing to worry about.

The obsession of dodging the issue of the PR people quoted in the article raised red flags all around my mind.


Here's a nice write up about the results: http://www.newscientist.com/article/mg22329872.600-artificia...

Note that the mice were given the human equivalent of 18 to 19 cans of diet soda a day.


This write up also only implicates saccharin in the harmful alterations of the gut flora, not other sweeteners. Yet the introductory text talks about artificial sweeteners are a group.

You cannot confirm the effects of "artificial sweeteners" as a category with an experiment that is based on saccharin. They are all different molecules. A bacterium that thrives on saccharin might not consume sucralose or aspartame.

Also glaringly absent is any mention of the sugar alcohols: sorbitol, xylitol, maltitol.

Who cares about saccharin. It is an outdated sweetener which is not widely used. Where can you find a diet soft drink or protein bar sweetened with saccharin?


First, I care, since saccharin is (was?) my preferred sweetener, for coffee, etc. Second, saccharin is very widely available at restaurants and so forth, coming in a very close second to aspartame, in my experience.


I know that it's available if you want it; but then, so are alcohol and cigarettes.

If a study could link popular, widely-deployed sweeteners found in processed foods and drinks, that would point to a big public health issue.

A problem with saccharin doesn't point to a wide-spread public health issue. Sacharrin has been vilified on and off over its entire lifetime. My parents' and grandparents' generation believed that it was a harmful poison, for instance; I remember hearing that as a kid. Only in the year 2000, in the US, were requirements for warning labels lifted, which had been in the effect since the 1970's, when saccharin was linked to cancer in rodents:

http://en.wikipedia.org/wiki/Saccharin#Warning_label_additio...

In spite of the lift, it doesn't seem that saccharin has made a comeback. Part of the reason could be taste. Particular mixtures of sweeteners are used in diet foods sweeteners in order to better simulate the taste of sugar.


People who use saccharine probably are unaware that that's what "sweet n low" or even "the pink packet" is.


Sweet'n'low packets are very common, and so are an easy way for anyone to get saccharin just by reaching into a jar.

Interestingly though, here in Canada, Sweet'n'Low is sodium cyclamate. Saccharin continues to be banned here as a food additive because of that (now long believed to be flawed) 1970's research which linked it to cancer.

I had no idea that Sweet'n'Low is saccharin south of the border!


Further, when Equal introduced saccharin and sucralose packets a few years back, it produced them in exactly the same color as Sweet n Low and Splenda, meaning that consumers can continue to just reach for the pink packet or yellow packet to get what they expect. There was some question about trademark infringement, I recall from somewhere. So, yeah, in the US, "pink" means saccharin.


From the Wiki article linked above:

The current status of saccharin is that it is allowed in most countries, and countries like Canada have lifted their previous ban of it as a food additive


Interesting. I also prefer saccharin, but I have to specifically buy my own to keep at home and the office. Everywhere else seems to, nowadays, have sucralose (more so) and/or aspartame (less so). This is in the UK, Ireland and South Africa.


As I mentioned partially elsewhere, in the US, you'll typically find aspartame, then saccharin, then sucralose. Almost every restaurant has all three already on the table when you sit, in case you order coffee or tea. If one's missing, it's probably sucralose. If only one is available, it's probably aspartame.

You can buy all these and other varieties in most grocery stores, but due to the history of when soda use exploded here in the 1980s, and the debunking of the old saccharin studies not becoming widely known until well after that, virtually all soft drinks in the US use aspartame, and I'm not aware of any that are saccharin only.


No, the study covered three sweeteners in mice. From the original study (paywalled, accessed via my university):

> To determine the effects of NAS on glucose homeostasis, we added commercial formulations of saccharin, sucralose or aspartame to the drinking water of lean 10-week-old C57Bl/6 mice

They found effects from all three sweeteners, though the strongest effects were from saccharin.

The followup study confirming the effects on humans, which was a much smaller study, only involved saccharin.


I, for one, care. About 100% of my artificial sweetener consumption is saccharin mixed in coffee or iced tea. I much prefer the taste over sucralose or others, but that preference is based on the assumption they are all otherwise biologically equivalent.


>You cannot confirm the effects of "artificial sweeteners" as a category with an experiment that is based on saccharin. //

Hmm. Yes you can, you just can't generalise the result.

If you want to test the hypothesis that "artificial sweeteners cause ..." then you start by testing if something from that category causes whatever effect. That shows that "artificial sweeteners cause the effect" but as you note it doesn't show that "all artificial sweeteners cause the effect".

Of course you follow up by looking at other sweeteners as this feeds in to understanding of the underlying mechanisms.

Logical analogy: Do birds sit on telephone wires? Yes, I saw one. Does that mean all birds sit on telephone wires, no. Indeed it's demonstrable that some birds never even see a telephone wire.


When you conclude the <category> has <trait> you are implicitly assuming that the elements of that category are somewhat representative.

If you only saw some pigeons sitting an the wire it would be better to conclude that pigeons sit on wires because the assumption that those pigeons are representative of pigeons is much more reasonable than assuming that those pigeons are representative of birds.

For a more contrived example I could do a study and conclude that liquids are poisonous. Technically true but extremely misleading.


When it comes to health effects, it's not necessary to prove that all members of a category share those effects. Simply showing that at least one member of the group is dangerous can be enough to recommend that people alter their behavior.

For example, not all snakes have venom that's harmful to humans. But some do and that's enough to assume than an unknown snake is venomous until it's been shown to be otherwise. Similarly, your "liquids are poisonous" study is enough to conclude that we shouldn't be ingesting liquids that haven't been shown to be safe.

Similarly, if we can conclude that one or more artificial sweeteners are harmful to our health, we can and should be consuming unsweetened foods until such time as individual artificial sweeteners are shown to be safe.


> it's not necessary to prove that all members of a category share those effects

You're assuming "artificial sweeteners" is a meaningful category, of the same kind as "snakes" or "liquids". Since the various substances in question are very different, chemically, I think that assumption requires more justification than just a bare assertion.


With pharmaceuticals the FDA customarily insists that "class effects", meaning adverse effects and black-box warnings, apply to all drugs considered to belong to a category. It doesn't even matter if a brand new drug is far less likely to produce certain "class effects" than prior drugs in the same category, the exact same warnings must still be listed.

In other words, the implicit rule is that drugs or additives in a class are "guilty" of potentially causing an adverse effect unless thorough study provides evidence that a member of a class does not produce particular negative effects. It's a high bar for manufacturers to get over and it's seldom attempted.

The FDA can assume serious adverse effects of one artificial sweetener apply to others, if the others are officially in the same class of substances as the first.



From that article:

> The dose of sweetener was the equivalent to the maximum acceptable daily intake in humans, as set by the FDA.

Now I realize that I, random commenter from the Internet, am unlikely to find a fatal flaw in an experiment designed and carried out by folks who do this professionally, but can someone explain to me why it's okay to give mice a human-amount of sweetener, and not a mice-amount?

It just seems to me that our larger bodies are probably better capable of handling... well, most everything, and to start dosing mice with human levels of sweetener is actually going to cause a much worse reaction than if humans were to consume that amount.

Edit: Also, it looks like the effects are reversible by "wiping" gut bacteria via antibiotics. If mice can survive the process of "wiping" gut bacteria, can humans? Is there a cure for this pre-diabetic state?


can someone explain to me why it's okay to give mice a human-amount of sweetener, and not a mice-amount?

This means that the mice got a dose per unit of body weight like what humans would get if they ate that FDA-defined maximum. That's what equivalent doses are taken to mean in animal models of human nutrition or medicine. When there is known to be a different bioavailability or digestive response in animals from humans, then the dose is adjusted with that in mind before the experiment begins.

So, no, the tiny bodies of mice were not subjected to the large servings that much bigger human beings eat. They got a dose adjusted for the body weight of mice.


it's more than just a "per kg" dosing as well. Rats/mice have a very different level of metabolism than humans do just because of scale.

Basically there's a fudge factor of 0.75. Of course, the following article goes on to explain that it's actually drug mechanism dependent as well. Very complicated stuff!

"The value of the exponent for whole body metabolic rate was originally calculated by Max Kleiber in 1932 to be 0.74 (Kleiber, 1932). A few years later, Brody et al. published their famous mouse to elephant curve and calculated the exponent to be 0.734 (Brody, 1945). A value of 0.75 is now accepted because it is easier to use, and the difference from 0.734 is considered to be statistically negligible (Schmidt-Nielsen, 1984). However, it should be noted that exponents in the range 0.6–0.8 have been reported for metabolic rate (Agutter and Wheatley, 2004). A value of 0.75 means that the whole body metabolic rate increases as body weight increases, but to a lesser extent than would be expected of a simple proportional relationship. It follows on from this that the specific metabolic rate (the metabolic rate per unit mass) decreases as animals get larger (the exponent is −0.25); the metabolic rate of 1 g blue whale tissue is 1000 times less than that of 1 g shrew tissue (Kirkwood, 1983)."

from:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737649/


Okay that makes a ton of sense, and I figured it was my own lack of understanding here. Thanks. :D


The paper contains some preliminary human data as well. From the New Scientist writeup:

But can the results in mice be extrapolated to humans? To find out, the team examined data from 381 people. They found an association between glucose intolerance and general sweetener use.

and:

To explore this, the team asked seven healthy people who don't normally consume sweeteners to eat the FDA's maximum daily allowance of saccharin. ... By day five, four of the seven people had a significant decrease in their glucose tolerance, while three saw no change. Sequencing showed that those who responded to the sweetener started out with different gut bacteria to those who didn't respond. What's more, the gut bacteria of the four responders changed significantly after consuming sweeteners, while the non-responders' barely changed.


Doesn't "equivalent to" in this case mean "the mice equivalent to the maximum accetptable in humans"?


It does.

I'm no experimentalist, but my naive assumption (gut feeling, heh) would be that the way to do this is to scale by body mass.


Almost, you scale by their metabolic weight. It's about 7 times higher for mice than for humans.

I'm not a scientist (heh) so the best explanation a quick google search gave was an article on CLA from the jn - journal of nutrition:

"The relationship between basal metabolic rate or energy expenditure and body weight in different size mammals is described by the function Y = aX0.75, where Y is basal metabolic rate (kJ/d), X is body weight (kg) and a is basal metabolic rate per kg0.75 per day, which is ∼300 kJ/ (kg0.75 · d). Thus, the basal metabolic rate in different size species is proportional to the body weight raised to the 0.75 power, the so called metabolic weight."

http://jn.nutrition.org/content/131/7/2067.full


That's a really charming synonym for 'scientist'


What, "experimentalist"? That's not a synonym for "scientist", it's a subset.

At least in physics, the main categories are "experimentalist" and "theorist". You'll sometimes find intermediate categories like "phenomenologist" (people who apply basic theory to make detailed predictions for experimental measurements) or "computational(-ist?)" (people who measure experimental-style results from simulations of basic theory).


I think we should add a third category, 'modeller', as in someone who runs experiments in silica. It's not really an experiment, and it's not really just theory.


Assuming I understand you, that's what I was getting at with "computational" scientists as a separate or intermediate category.


The theorists disagree with you, and I'm sure they have a long paper with lots of equations explaining why.

(it's a joke)


Not quite. Scientists also come in the Theoretician variety.


From the paper:

"To examine the effects of pure saccharin on glucose intolerance, we followed a cohort of 10-week-old C57Bl/6 mice fed on HFD and supplemented with 0.1 mg ml 21 of pure saccharin added to their drinking water (Extended Data Fig. 1c). This dose corresponds to the FDA acceptable daily intake (ADI) in humans (5 mg per kg (body weight), adjusted to mouse weights, see Methods)."


I read "was the equivalent" to mean "Is the same ratio of grams of sweetner to pounds of mouse-flesh as the maximum ratio set by the FDA," not "is the same numeric amount."


A cure is clearly fairly likely for this particular pre-diabetic state. It does cure the problem, but the exact effects wiping out gut bacteria is not terribly well understood. In fact, this is one of the more interesting areas of research... beyond just the direct applicability to human problems, this provides a very interesting data point about how exactly gut bacteria coexist with us.


Whenever you take antibiotics, you typically 'wipe' gut bacteria. Maybe not to the same degree as in a clinical trial, but you certainly kill a lot -- healthy and unhealthy alike. Which is why several medical practitioners will prescribe/advise you take probiotics alongside the anti-, to promote good health.


There is colon hydrotherapy when the doctors fill your intestines with water. They use it for several reasons including candida elimination. So humans can survive "wiping".



For those not aware, other studies have shown that consuming diet soda may actually increase the chance of obesity. So that is not necessarily news. If you are curious, here is a pretty good study (full text):

http://onlinelibrary.wiley.com/doi/10.1038/oby.2008.284/full

More recently, studies have tried to determine whether there is a satiety or protein mechanism that can explain this, whereas this new study demonstrates that gut flora may play a role.

This needs to be confirmed, and there may still be other mechanisms at play as well, but it is interesting.

(Disclaimer: I do have a healthcare background, but am not a researcher in this field. Would be happy to hear more from anyone who is.)


Indeed. I think it helps to unpack the various claims being studied:

1) Carcinogenicity. Do certain sweeteners cause harmful mutations and increase cancer risk? This is one of the oldest and most frequent allegations, especially against saccharin and aspartame. Mostly inconclusive, though both sweeteners have been exonerated at least as often as they've been accused.

2) Insulin triggering. Artificial sweeteners may not bear the caloric load of sugars and starches -- but do they trigger the release of insulin, just the same? Again, the jury is still out, but certain sweeteners (aspartame, sucralose, and possibly saccharin) are looking suspect.

3) Caloric load. Some sweeteners and putatively indigestible molecules (sugar alcohols, "resistant starches," etc.) may contain more effective calories than in vitro studies predict them to contain. This is because the chemicals aren't digested in the traditional sense, but are fermented and absorbed in the gut. Caloric bioavailability is often different from nominal calorie count. (Indeed, this is the entire principle behind the supposed benefits of resistant sweeteners and starches; those benefits may have been overstated or misunderstood).

4) Disruption or adverse selection of gut microbiota. As detailed in this study. While not all sweeteners have been implicated here, this field of study is only just kicking into high gear. It seems reasonable to suspect that molecules fermented by / consumed by gut bacteria could have some effect on flora composition. Many sweeteners fit that criterion.

5) Other toxicities. Liver or kidney toxicity, neurotoxicity, endocrine disruption, etc. As with carcinogenicity, the jury is still out. Unlikely for some sweeteners that are not metabolized via these pathways. Possible for others. Most sweeteners (all?) on the market right now are generally recognized as safe in this respect, despite popular beliefs to the contrary. Notable exceptions exist for those with rare metabolic or genetic disorders, such as phenylketonuria (aspartame contains phenylalanine).

6) Side effects. Some sweeteners, particularly those in the sugar alcohol family (and sorbitol especially), can cause laxative effects and other GI-related issues. Individual tolerance can vary. Breaking this category out from #4 because the action here can be purely mechanical (i.e., increasing intestinal water absorption).

I'm not a doctor or medical researcher myself. Just an interested nerd. But I have been following this area for awhile. I welcome any corrections, comments, or additions from people more knowledgeable than I am. I assume there are many such people on HN. :)


Good list. Among the patients I see metabolic disturbances rank high on the list problems to manage. Some people complain of adverse effects of NAS such as headache, GI symptoms, but in the clinical setting, it's very hard to establish connections between NAS and metabolic syndrome manifestations like DM2.

The article says mouse fed any of 3 common NAS in water with/without glucose developed "glucose intolerance", which I take to mean above-normal glucose levels. That would point to either impaired insulin production or increased insulin resistance. I think the latter is much more likely.

This probably occurs in some humans too (among people genetically predisposed to develop DM2). Of course that's my extrapolation of the info, but seems a likely direction of future research. Getting insulin levels and measuring insulin resistance after NAS feeding are logical steps to take.

I agree with your comment and others that the role of colon microorganisms is a truly fascinating subject, and remains quite a mystery. Other research shows gut flora are distinct among host species. The evolution of these microbes appears intimately bound to the evolution of their host, but the nature of the link is unknown. Odds are unraveling the story of the numerous friends within (and all over) us will fill in important gaps in our knowledge in surprising ways.


> may actually increase the chance of obesity

Also, diet soda may decrease the chance of obesity by up to 100%! And may may may.


"may" can always be replaced by "may" or "may not" and also see Betteridge's law of headlines which is somewhat related


Exactly


I keep drinking diet soda and I still can't gain weight (news: big eaters get fat)


The headline is suspicious, but unfortunately, this article is paywalled, so I can't tell what's really going on. The main problem with the headline is that it lumps together "artificial sweeteners" as a category, when that is in fact a pretty widely varied class of molecules.


Agreed. From the article Nostromo just posted[1], looks like the mouse models were based on aspartame, saccharin, and sucralose, and the human subjects were taking saccharin.

[1] http://www.newscientist.com/article/mg22329872.600-artificia...


FDA acceptable daily intake (ADI) for aspartame is 50 mg per kg of body mass.[0] For an individual 180 pounds, that's about 82 kg. That means his ADI is 4100 mg. Aspartame in popular diet sodas is between 50 and 125 mg.[1]

You'd have to drink A LOT of diet soda to reach these levels.

[0] http://www.cancer.org/cancer/cancercauses/othercarcinogens/a...

[1] http://static.diabetesselfmanagement.com/pdfs/DSM0310_012.pd...


I have a friend who used to drink nothing but Diet Coke. He went through a few 2l bottles a day. According to that link (assuming it's the same in Europe), Diet Coke is 125mg per 8 ounces, so a 2l bottle is 125 / 8 x 70.4 = 1100mg. So if he drank four 2l bottles, that's over the daily limit.


This is an impressive piece of work but I worry that a larger amount of work is needed in the relationship between glucose intolerance, diabetes and metabolic syndromes in general. The fact that glucose intolerance is induced by a high sugar diet and leads towards a path of clinical outcomes ending in diabetes, doesn't necessarily indicate that glucose intolerance developed via artificial sweetener consumption is indicative of being on the same clinical pathways towards metabolic syndrome and diabetes.


I'd be curious if they tried this study with xylitol. I chew xylitol gum for dental health and from my understanding it's not thought to contribute to metabolic problems in reasonable quantities:

http://en.wikipedia.org/wiki/Xylitol#Diabetes


Xylitol was not included in the study. Because xylitol is absorbed more slowly from the gut and gut microflora appear to be the mechanism of action found in this study, I'd personally be at least a little concerned.

Mice in this study were given sweeteners for 11 weeks, long enough that their use apparently led to changes in microflora which were associated with glucose intolerance. Existing studies of xylitol could well be for much shorter lengths of time and might not have been able to detect these kinds of changes.


I wonder then if its the absorption of the gut or if it is the conditioning. If the gut flora have to adapt to trying to break down an impenetrable compound they might become super strong at breaking down simpler molecules no?


"from my understanding it's not thought to contribute to metabolic problems in reasonable quantities"

Xylitol is quite toxic to some animals, such as dogs tho.

http://www.vcahospitals.com/main/pet-health-information/arti...

edit: this snippet maybe worth highlighting

In both humans and dogs, the level of blood sugar is controlled by the release of insulin from the pancreas. Xylitol does not stimulate the release of insulin from the pancreas in humans. However, when non-primate species (e.g., a dog) eat something containing xylitol, the xylitol is quickly absorbed into the bloodstream, resulting in a potent release of insulin from the pancreas. This rapid release of insulin results in a rapid and profound decrease in the level of blood sugar (hypoglycemia), an effect that occurs within 10-60 minutes of eating the xylitol. Untreated, this [canine] hypoglycemia can be life-threatening.


That doesn't help much, though. There's all kinds of things that are toxic to one species and not another, even just in Mammalia, and everything that anything anywhere ever eats is definitely not good for some other species.


The mechanism of toxicity (in dogs) is specifically relevant. There are multiple studies showing that artificial sweeteners in general are unhealty -- the body recognizes them -- and takes a variety of actions as a result.

Clearly these reactions in some cases may be simply performance related (see: http://www.gssiweb.org/Article/sse-118-carbohydrate-mouth-ri...). Whilst others can be catastrophic (see: xylitol in dogs).


From the caption on one of the figures (which is all I can access without buying the article) "NAS; saccharin, sucralose and aspartame". So I don't think they tried xylitol.


Agreed, or stevia (which is found in some high-priced colas, among other products).

http://en.wikipedia.org/wiki/Stevia


Does this mean diabetes could (in some cases) be caused by gut bacteria? Can we reduce diabetes risk factors with targeted antibiotics that attack certain glucose-intolerance-causing bacteria?


It's fiendishly difficult to pry apart correlation and causation for complex conditions like diabetes (which we're steadily reconceptualizing as less of a "disease," and more of a chain reaction of metabolic and hormonal disorders). Changes in gut bacteria are associated with the condition sometimes called "pre-diabetes," or a "pre-diabetic state." But we're not yet sure if they are a causative factor, if they are the result of the condition, or if they're simply co-morbid with it.

Whatever the case, gut bacteria appear to play a vital role in our metabolic health, and we're only beginning to explore this area in earnest.


Yes, absolutely possible. There is so much potential in gut bacteria research and we are only starting to recently scratch the surface with it. I get really excited about the topic of gut bacteria for some reason, it is just very interesting.

Its hard to separate cause and effect right now though. There also may be a snowball effect. We just know so little so there is a lot of research that needs to be done.

Antibiotics are unlikely. Fecal transparents are much more likely. Fecal transparents are starting to be used for c. Diff infections with success.


There's also some indication from other studies that antibiotics killing off symbiotic gut flora may be implicated in diabetes.


This result seems pretty strange to me - why would artificial sweeteners affect bacteria's metabolism in this way?

It seems like a bizarre coincidence that bacteria would react in the same way to three different sweeteners, unless they have receptors that happen to match human taste receptors (which also seems unlikely). In other words, to bacteria these sweeteners should just seem like unrelated random chemicals.

(I read the Nature paper - most of it looks at saccharin since that had the strongest response, but all three artificial sweeteners caused marked glucose intolerance.)


Bacteria are, in general, much more capable at processing various chemicals than humans are. They can even pass around packets of genetics, called plasmids, across species. So it isn't really surprising if bacteria can flourish eating something that tastes sweet to people, but doesn't provide any calories to people. There have been some artificial sweeteners shown to hurt bacteria more than people - Xylitol is famously used in gum, for example, because it costs bacteria energy to try to eat it, but they gain nothing, thus helping to fight bacteria growth.


Aspartame is essentially just a collection of amino acids, so it's even more feasible (in a total guessing hand-wavey way) that gut bacteria would be affected.


Well, not everything makes immediate intuitive sense.


Yeah, that's pretty much the whole reason we need science.


This seems misleading.

If you go through the graphs and results, what emerges is that only the sweetener saccharin has that altering effect on the gut bacteria. I cannot find among the results any claim that the other NAS that were studied (sucralose and aspartame) have the effect.

The thing is that saccharin is not widely used any more. If saccharin is found to be harmful, that is nice to know, but not highly relevant.


The New Scientist article notes that four of the seven human subjects who consumed three to four sachets of sweetener a day saw a significant change in their gut bacteria.

As someone who has consumed significantly more than that for a very long time, my question would be, did their gut flora reconstitute itself after they stopped using the sweetener? And if not, how could you go about repopulating your microbiome short of a stool sample?


The gut flora is as resilient as any other part of human body. It might take a significant time though. I've heard Korean food helps a lot because it's fermented. Also usual bifido youghurts you'll find at any grocery store.


The does in the article is higher than your post: 3-4 sachets taken 3 times a day.

Those packets to me are sweet. I alternate between honey and half a packet in my tea.

Gut Flora do come back (eg after taking antibiotics which cuts them down). They're crowded in there, so the ratio of them is important. Everyone has different ratio and there is no easy way to measure and control that.


A probiotic might help. A gastroenterologist once recommended Align to me, if that's helpful to you.


This seems very misleading. The abstract (available without paywall) mentions a group of sweeteners, whereas the findings seem to show that only saccharin has these negative effects. I feel like NAS are probably bad, but without evidence to support it they should not claim that in the abstract.


For some biological context, we have taste receptors in our digestive tracts identical or nearly identical to those on our tongue, only the ones in our digestive tract are not hooked directly to sensory neurons, but instead trigger endocrine signals and such. Since the receptors are identical, then anything that tastes sweet on your tongue will activate these receptors as well. If I recall my metabolism course correctly, studies have found that artificial sweeteners can trigger insulin release through these receptors in the same way as real sugar (leading to possible hypoglycemia as your body compensates for a rush of sugar that never comes).

So basically, I have no trouble believing that artificial sweeteners can have many of the same long-term health effects as excessive consumption of real sugar, since they're already known to have many of the same short-term effects, including effects on insulin regulation.


So given a choice, between Diet Soda vs. Normal Soda, what would be worse for your overall health?

I imagine even with increased glucose intolerance, you're still better off choosing Diet?


You're probably better off not choosing carbonated liquid candy -- especially not doing so regularly and in significant quantities -- even if the sweetener happens to be non-caloric.

And the point where you've reduced your choices to regular soda vs. diet soda, you've already failed.


Along the same lines, there's no point in comparing the effectiveness of different forms of birth control because only abstinence is 100% effective.

Sometimes people want to eat and drink things because they taste good. There's nothing wrong with that, and we should be supportive of making marginal improvements rather than dismissing anything other than radical change.


Failed at what?


Failed at having a healthy diet. (That is, if he does make that choice frequently - a one time event probably won't change anything.)


In what way is it unhealthy? Aspartame has zero calories, and decades of studies showing its safety.

Put another way, if you want to avoid sugar (which is much less healthy than aspartame), besides water, there's tea, coffee, flavoring mixes like Crystal Light, and various prepared sugar free soft drinks. Many prefer variety over water. There's little scientific basis to believe drinking any of these things are bad. Drinking a mix of these is quite a bit healthier for an adult than chugging juice or sugared drinks - unless you're explicilty trying to carb-load. Milk is a healthy alternative but debatable due to its effects on some.


Not a direct answer, but noting that there's also a third choice, which is to not drink anything sweet. I'll chug a diet soda once in a while because what's the downside? But in light of new compelling evidence I might change that habit without too much fuss.


Diet. Artificial sweetener concerns aren't much different from "cell phones cause cancer" fears. Meta-analyses of decades of aspartame research shows it is safe.

Sugar, in liquid form, on the other hand - not so much.

Eg. http://www.ncbi.nlm.nih.gov/m/pubmed/12180494/


C: Ice Mint Rooibos Tea, lemon water, lime water, green tea, sparkling water with a dash of lime (not "lime flavored bottled water, which usually contains sweeteners). If none of those satisfy your tongue, you might look into diet adjustments to re-calibrate your flavor response.


I can recalibrate my taste buds in all manner of ways, and sparkling water with a dash of lime will never even be in the same satisfaction category as an ice cold Coke Zero in a sunny day.

Had you mentioned a good lager, you'd have a contender, but there's another slew of health issues there.

In the end, living is slowly killing me. Let's just focus on the slow part and not fret about small risks.


Diet soda is better than fat soda. Better train yourself to drink plain soda water (if you like carbonation) or just tap water.


Depends on how much you're consuming.


I'm not really surprised Saccharin isn't great for you personally- but this isn't so damning there are many other artificial sweeteners to choose from.

https://en.wikipedia.org/wiki/Sugar_substitute#Artificial_su...

I'd of course like to see them all studied in this manner.


I hope this doesn't hold true for stevia as well :/


Pure stevia is not artificial, but the verdict is still out on safety. It seems to be OK... for now. I use it, though I try to use honey as well.


The stevia whole leaf has been used for centuries in teas on Brazil. It has been used as an artificial sweetener in Japan for decades accounting for around 40% of the sweetener market there. Weirdly, I always bought it labeled as a dietary supplement in the US before the FDA approved some extracts as food additives.


That was my first thought too, I use stevia in almost everything.


Overall, this was a nicely done study. The microbiome is fascinating and an exciting area of research.

One criticism however would be that the dose of artificial sweetener tested was atypically high.

It'll be neat to see further research into the cause of variable responses of the subjects to the artificial sweeteners.


According to the New Scientist article others have linked to, the equivalent human dose was 9-12 packets of sweetener a day. I'm sure there are heavy coffee drinkers that go through that much.

I also don't like those studies where the human equivalent dose is like 50 pounds of sweetener a day, or something silly. This one isn't so bad.


I guess I'm having trouble figuring out where the numbers are coming from.

I'm seeing that the FDA recommended maximum dose for aspartame is 50mg/kg/day. Assuming a 70kg Standard Man, that's 3.5g/day of aspartame. Diet Coke has 125mg per 12oz. can, so that would be 28 cans/day. Each packet should be around 35mg aspartame, so 100 packets/day (the amount of aspartame per packet was hard to find, and the approx. was from an American Cancer Society article).

Agreed that 9–12 packets doesn't sound like much, but I think we're talking way more than that.


For comparison, that amount of sweetener (9-12 packets) is found in about 3 cans of Diet Coke (35mg aspartame per packet, 125mg per Diet Coke). I suspect there are quite a few people who consume more than that in a day.


The industry takeaway should be to try to isolate the bacteria that play the secondary part in the glucose resistance, then put ANOTHER additive in the drinks to kill that bacteria, then sell a more expensive NEW zero calorie drink?

People like sweet. Let's make sweet safe.



This raises more questions than it answers I think (which is a good thing)

1 - Is there such thing as a "sweet base"? Our tongues perceive sweeteners as sweet (duh) but it seems it mimics sugar in a way for bacteria as well.

2 - From the article "Wiping out the rodents' gut bacteria using antibiotics abolished all the effects of glucose intolerance in the mice. In other words, no bacteria, no problem regulating glucose levels."

Soooo... Bacteria affects absorption of glucose? They consume it? They change the intestinal PH? Or something else?


Can someone post the full paper? The charts shown at the bottom seem to contradict some of their conclusions and implications. For example, some of the sweeteners seemed to result in lower chow consumption and increased energy expenditure. That would be a positive effect that isn't mentioned in the abstract.


Can anybody explain or guess what the consequences of this intolerance are or could be?



You might find this video on fructose and metabolic disease (of which glucose intolerance is a symptom) interesting:

http://www.youtube.com/watch?v=dBnniua6-oM


It's worth noting that there are many critics of this guy.


True. As I understood them though, the criticism was primarily about his message that fructose would be the key or only reason of metabolic syndrome, or his depiction of sugar as pure evil rather than as something which you can consume in small amounts, more than about the effects of fructose itself. (When not, connections between the critic and the sugar or food industry were quick to Google, thereby reducing the credibility to zero.) This may have changed since I spent time digging into it, though, so please expand if it has.


My point was just to point out that criticism exists. Loads of people watch that video and don't do other research on the topic.


Do they compare pure sweetener diet with pure sugar diet calorie per calorie, and sweetness units per sweetness units? Sweeteners are still caloric, the point is that they provide the same sweetness for less calories.


Raised insulin levels are much more complicated than we once thought. You can get an insulin response from artificial sweeteners just swished in your mouth and spat out. Solution, eat real food when you can


Do you have a source for that? The last time I checked this worked with mice, but humans showed no insulin response from sweet taste alone.


https://www.ncbi.nlm.nih.gov/pubmed/18556090, "Cephalic phase insulin release in healthy humans after taste stimulation?". The abstract ends, "In conclusion, the current data suggest that the sweeteners sucrose and saccharin activate a CPIR even when applied to the oral cavity only." Just, Pau, Engel, Hummel 2008. Appetite. 2008 Nov;51(3):622-7. doi: 10.1016/j.appet.2008.04.271. Epub 2008 May 10.

I appreciate that you posted a comment instead of just downoting. The fucking ignorant downvoting prick squad is a key reason that I mostly gave up commenting here.


Oops, I didn't realize I was logged into abecedarius's account still on this machine. Reposting my inflammatory comment as me.


I don't right now, but from my times when competing, I used to read a lot of science based research on nutrition and there was a study that said swishing a carb rich liquid was enough to trigger it.

I think I first saw it referenced on an old edition of 'The Complete Guide to Sports Nutrition' by Anita Bean


Artificial sweeteners are not "carb rich". That's kind of the point of them...


What I meant was there is a possibility of it happening as a sweet taste (parent didn't mention sweeteners, just sweet taste) response since there is a similar response to carb rich drinks (study didn't mention the kind of carbs so no idea)


Are you referring to the salivary amylase mechanism? Sounds similar but actually requires starch to be activated.

I'm aware of no RCT or even epidemiological research to suggest that NAS causally mediates insulin response.


Doesn't seem so strange - if you create a sugar deficit in your body by significantly reducing your intake, wouldn't you expect the body to be more responsive to sugars when it encounters them?


I believe that's why they had a control group with unsweetened water.


Now let's see a human study where people who consume those sweeteners, eat carbohydrates in moderation, and exercise regularly are still at increased risk for diabetes.


"metabolic abnormalities"

Anyone know if they go into these into the paper? Really want to know what else is in the paper; I chew way too much sugar-free gum.


Most sugar-free gum uses some type of sugar alcohol (e.g. xylitol, erythritol). These are not technically-speaking considering NAS. Their mechanisms of absorption vary wildly and, while in some cases they can cause digestive stress in large amounts, there is no good evidence AFAIK that they have a deleterious effect on gut microbiota.


I chew way too much sugar-free gum.

At first I thought, yeah, this will never be a problem for me, then I realized the only thing I do consume with artificial sweeteners is gum. I do hope the doses are low enough not to be a problem, but I want to know!


Based on the doses they used you'd have to chew multiple packs of gum per day to get the same amount of sweetener.


People rarely consider how what you eat affects your microflora which then affects various other systems and may even affect your desire to consume.


Without delving into a bunch of scientific papers, how could I go about considering how my dietary choices influence my microflora for better or worse?


Well, you can't really do that. We don't know nearly enough about it. Hell, we're not even good at normal dietary science yet and the whole gut bacteria science field is really new.

You can find a healthy and fit person and get them to give you some of their gut flora and then eat it. That could probably work. It also might make you sick (I imagine) and it's terribly disgusting: "On a scale from swallowed to poo, how do you want my eaten food?"


I don't think that would work (bacteria living the colon can not necessarily survive all the way through the digestive tract). What is an accepted form of gut biome therapy is a stool transplant:

http://en.wikipedia.org/wiki/Fecal_bacteriotherapy


Could it work if put in capsules dissolving in the right stage? Anyway, thanks for the link.


"You don't." Now, that's slightly hyperbolic for effect, but let me clarify: We know SO LITTLE about actual correlations between gut microbiome and how it impacts the body in the long term. We can barely even correlate a single given feature of your gut as being related to, say, obesity. (My partner spent some time in a lab asking this precise question; I will, if I can get a source, give some sort of paper link when I get home from work) There's a lot of fad science around diet and microflora nowadays, but the sense I get as an observer of someone who is in that field, it's about as wishy washy as if you asked a computer scientist "what are the leading causes of disk failure." We know that if you shove a screwdriver through it it won't be happy, but there's still tons of debate about the finer points. (And your gut is WAY more complex than a HDD).

So, takeaway from this ramble, do what your body responds well to, and keep to generally "good patterns" of hygene and balanced diet. Anecdotally, and from many practicing physicians, this tends to work out "ok" in the long run.


The woman who wrote this book has been gathering anecdotal evidence for decades on the topic "simple sugars vs complex sugars", and claims that her diet of simple sugars helps about 80% of people with GI problems: http://www.breakingtheviciouscycle.info

I've followed some of its advice and have been very happy with it.

The main takeaway is this: Fructose and glucose are easily absorbed in the small intestine, while complex carbs are not. Instead, they are fermented mainly in the large intestine, by bacteria that specialize on that over time. The problem might be worsened by insufficient stomach acid and digestive enzymes (e.g. weakened pancreas). If you have a microbiome that has tilted towards a non-optimal constellation, then you can do damage control by eating as few complex carbs as possible for a time. That means no sugar, no grains, no potatoes or rice, not even sweet potatoes or yums. The book also recommends to employ powerful probiotics (e.g. homemade yogurt that ferments for 24h). I personally have been doing water kefir for a time (which is a wild ferment, so a bit risky) and this helped my IBS a lot. I might take a ubiome test sometime and check what exactly is wrong with my microbiome.


This is the same thing with having good oral hygiene. So many serious health problems can be traced back to poor oral hygiene.

If you go nothing else, make sure you take good care of your mouth, gums and teeth!


The maximum dose is quite high, but does the effect also occurs when consuming more sane dosage a day?


I'm paywalled out of seeing the whole article until I try a workaround (after which I may expand this comment), but I think we can all see the abstract of the article if we follow the link kindly submitted here. Yet some questions in other comments raise issues that are already responded to by the article abstract. Here is the full text of the article abstract available in the free view at the link:

"Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage."

AFTER EDIT: After reading all the comments in this thread to the time of this edit, I see that some participants here disagree entirely with how I commented at first (as above). I note their opinion with interest and say here for the record simply that I saw previous comments that raised questions about information that is available in the article abstract for all of us to read. I meanwhile did find my workaround to get the full text of the article (I have library access with journal subscriptions for one aspect of my work, which is rather slow and buggy) and from the full article text I see that the experimental approach the researchers tried--feeding mice with the artificial sweetener to see if that changed gut microbiota in the mice, and then transferring the gut microbiota to other mice--did indeed bring about clinical signs consistent with the idea that the sweetener itself might cause related clinical signs in human beings.

"To test whether the microbiota role is causal, we performed faecal transplantation experiments, by transferring the microbiota configuration from mice on normal-chow diet drinking commercial saccharin or glucose (control) into normal-chow-consuming germ-free mice (Extended Data Fig. 1e). Notably, recipients of microbiota from mice consuming commercial saccharin exhibited impaired glucose tolerance as compared to control (glucose) microbiota recipients, determined 6 days following transfer (P < 0.03, Fig. 1e and Extended Data Fig. 2e). Transferring the microbiota composition of HFD-consuming mice drinking water or pure saccharin replicated the glucose intolerance phenotype (P < 0.004, Fig. 1f and Extended Data Fig. 2f). Together, these results establish that the metabolic derangements induced by NAS consumption are mediated by the intestinal microbiota."

This preliminary finding, which of course needs to be replicated, has caused alarm in the industry, according to the link participant nostromo kindly shared in this thread.[1] There is epidemiological signal that human beings who consume a lot of artificial sweeteners are not especially healthy people compared to people who consume few. Teasing out the mechanism that may underly that observational finding will take more research, but this is important research to get right.

"To study the functional consequences of NAS consumption, we performed shotgun metagenomic sequencing of faecal samples from before and after 11 weeks of commercial saccharin consumption, compared to control mice consuming either glucose or water. To compare relative species abundance, we mapped sequencing reads to the human microbiome project reference genome database16. In agreement with the 16S rRNA analysis, saccharin treatment induced the largest changes in microbial relative species abundance (Fig. 2a, Supplementary Table 2; F-test P value < 10−10). These changes are unlikely to be an artefact of horizontal gene transfer or poorly covered genomes, because changes in relative abundance were observed across much of the length of the bacterial genomes, as exemplified by one overrepresented (Bacteroides vulgatus, Extended Data Fig. 7a) and one underrepresented species (Akkermansia muciniphila, Extended Data Fig. 7b)."

The authors sum up their experimental findings by writing

"In summary, our results suggest that NAS consumption in both mice and humans enhances the risk of glucose intolerance and that these adverse metabolic effects are mediated by modulation of the composition and function of the microbiota. Notably, several of the bacterial taxa that changed following NAS consumption were previously associated with type 2 diabetes in humans13, 20, including over-representation of Bacteroides and under-representation of Clostridiales. Both Gram-positive and Gram-negative taxa contributed to the NAS-induced phenotype (Fig. 1a, b) and were enriched for glycan degradation pathways (Extended Data Fig. 6), previously linked to enhanced energy harvest (Fig. 2c, d)11, 24. This suggests that elaborate inter-species microbial cooperation may functionally orchestrate the gut ecosystem and contribute to vital community activities in diverging environmental conditions (for example, normal-chow versus high-fat dietary conditions). In addition, we show that metagenomes of saccharin-consuming mice are enriched with multiple additional pathways previously shown to associate with diabetes mellitus23 or obesity11 in mice and humans, including sphingolipid metabolism and lipopolysaccharide biosynthesis25."

There have been a lot of questions raised in this thread, and indeed the article itself raises plenty of interesting questions to follow up with further research. When discussing a new preliminary research finding like this, we can work outward from the article abstract to news reports about the article findings to the article text itself to focus on the known issues and define clearly the unknown issues. I appreciate comments from anyone here about how I can help contribute to more informed and thoughtful, in Hacker News sense of "thoughtful,"[2] discussion of research on human nutrition.

Other comments here asked why we should respect journal paywalls at all, and the basic answer to that question is a basic principle of economics, that people respond to incentives. (That's the same reason you don't found a startup that you expect will always lose money for all time.) Nature is one of the most-cited scientific journals in the world, so it's a big coup to be published there, and that means Nature gets a lot of submissions. To slog through all the submissions with adequate editorial work does cost money. (I used to be a junior editor of an academic journal.) The article gets more attention (it has received a lot of attention in this thread) if it is in a better rather than worse journal. Some journals are lousy enough to publish anything, and those journals beg for submissions, but Nature can charge for subscriptions and impose paywalls (which expire for government-funded research, with author sharing of author manuscripts on free sites usually being mandatory after a year embargo) because what it publishes is often worth reading (as here).

AFTER ONE MORE EDIT:

I see that while I was reading the fine article from Nature submitted to open a thread, my comment is now part of a thread that is about the New Scientist popular article on the same research finding. This will be confusing to readers newly visiting this thread. The title of the Nature article is "Artificial sweeteners induce glucose intolerance by altering the gut microbiota" (the Hacker News thread title I saw, per the usual rule of using the article headline as the submission headline) and the article DOI is

10.1038/nature13793

for the full article published online (behind a paywall) on 17 September 2014.

[1] http://www.newscientist.com/article/mg22329872.600-artificia...

[2] "The most important principle on HN, though, is to make thoughtful comments. Thoughtful in both senses: both civil and substantial."

https://news.ycombinator.com/newswelcome.html


> I see that while I was reading the fine article from Nature submitted to open a thread, my comment is now part of a thread that is about the New Scientist popular article on the same research finding. This will be confusing to readers newly visiting this thread.

Incidentally, changing the source article after active discussion -- and especially to a secondary source when the original link is to the primary source -- is a really bad idea, even given the understandable and justifiable preference for non-paywalled sources.



thank you


I meant to downvote your comment but accidentally upvoted it.

You wrote that you have nothing meaningful to say and quoted the abstract, contributing nothing to the conversation. Next time, instead of using your accumulated karma to monopolize the top spot while saying nothing, just say nothing.


> instead of using your accumulated karma to monopolize the top spot

You only get to the top spot in a comment section by getting that specific comment upvoted there.

... at least, that's certainly how I would expect it to work! If the site gives preference to comments based on preexisting karma, at least after any upvotes have been cast, then that would be highly disappointing.


The site gives preference to comments based on preexisting karma, especially shortly after they're posted.


I found it helpful. I don't really want to even bother with paywalled sites, much nicer to just read the abstract here.


The abstract is not paywalled. I understand that my comment may seem rude, but tokenadult's basically useless comment was in the first spot for a good half hour, above a better comment thread, until I posted and several readers downvoted it.

In my opinion, tokenadult abuses his high karma average somewhat too often. Here's how it works: if you have a high comment average, your comment sorts higher than others with a similar number of up-votes. So if you post early enough, before anybody has written anything very interesting, your comment will stick to the top. If it's even vaguely useful to the casual reader—you post an article abstract copied and pasted from the the submission, say—you can then hold down the top comment spot, garner a lot of up-votes, pad your average, and stifle a more meaningful discussion. Maybe you come along later and edit in some actual information.

I find it obnoxious, and I wish tokenadult would stop doing it. (And I really only commented because I accidentally upvoted him, prolonging his comment's contentless primacy.)


So the public funds studies, which they give to journals for free, who then sell access for $3.99/view. I'm really not sure this was the "free exchange of ideas" which science is based upon.

Even the New York times only charges $3.75/week (the nature price is per article/view NOT per week, it would be $4.14 if their $199 plan was weekly) and the NYT has to actually pay journalists to create the content. Nature gets all their content for free.

So what are Nature's expenses anyway? They no longer have to type set as it is just an identical PDF which is sent to them. Is hosting and management of the web-site really so costly that it is $3.99/article?


> So what are Nature's expenses anyway?

The prestige. (theoretically that means organising the peer review part of science and such)


Nature has the highest impact factor of any research journal. They can basically ask for whatever they want at this point, because someone out there will be willing to pay it to get their paper in nature.


The peer review process, I would think.


They don't pay for people to peer review as far as I know.


That the individual peer reviewers aren't paid does not imply that coordinating the peer review process is cost-free to the publication.


Nope, peer review is done by unpaid volunteers as well.


Sure, but they have a layer of editors/reviewers to filter out the bullshit.


Isn't that actually peer-reviewed too?


Peer review has always been on a volunteer basis.


iirc authors have to pay Nature to submit their articles as well.


Diet soda makes you fat.


Sweeteners are suspected to have downed the Roman empire (via lead poisoning), so, learn from history and just change your taste norm and you'll live longer and happier. I had a sweet tooth once and it took about a couple of years to even not being able to tolerate it. The weak find excuses, the strong adapt and improve. Just reject anything with refined sugar or fancy new "healthier" sweeteners - do you like sugar more than tomorrow? Cane sugar is not healthier than HCFS (it might be just slightly less harmful). Agave "Nectar" actually has significantly more fructose than HCFS... and it's not unprocessed as claimed, and so on. Stevia is slightly different, the plant has other benefits, but I wouldn't ever use the adulterated version (Reb A or whatever). Hack your taste buds, hackers!


Sugar alcohols (xylitol, sorbitol, maltitol, mannitol, erythritol) have the same negative effect on the gut microbiota.




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