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.
Note that the mice were given the human equivalent of 18 to 19 cans of diet soda a day.
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 It is an outdated sweetener which is not widely used.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?
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.
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.
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!
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
> 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.
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.
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.
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.
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.
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.
There is also http://www.economist.com/news/science-and-technology/2161331..., via https://news.ycombinator.com/item?id=8331143.
> 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?
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.
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:
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.
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.
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."
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).
(it's a joke)
"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)."