Sugar is toxic to mice in 'safe' doses, study says

A mouse emerges from its territory to investigate a food resource. Researchers at the University of Utah studied mice in semi-natural “mouse barns” to reveal that sugar is toxic to mice in doses proportional to those now considered safe for humans – the equivalent of a healthy human diet plus three sweetened soda drinks daily. Credit: Douglas H. Cornwall, University of Utah

When mice ate a diet of 25 percent extra sugar – the mouse equivalent of a healthy human diet plus three cans of soda daily – females died at twice the normal rate and males were a quarter less likely to hold territory and reproduce, according to a toxicity test developed at the University of Utah.

"Our results provide evidence that added sugar consumed at concentrations currently considered safe exerts dramatic adverse impacts on mammalian health," the researchers say in a study set for online publication Tuesday, Aug. 13 in the journal Nature Communications.

"This demonstrates the of added sugars at human-relevant levels," says University of Utah biology professor Wayne Potts, the study's senior author. He says previous studies using other tests fed large doses of sugar disproportionate to the amount people consume in sweetened beverages, and candy.

"I have reduced refined sugar intake and encouraged my family to do the same," he adds, noting that the new test showed that the 25 percent "added-sugar" – 12.5 percent dextrose (the industrial name for glucose) and 12.5 percent – was just as harmful to the health of mice as being the inbred offspring of first cousins.

Even though the mice didn't become obese and showed few metabolic symptoms, the sensitive test showed "they died more often and tended to have fewer babies," says the study's first author, James Ruff, who recently earned his Ph.D. at the University of Utah. "We have shown that levels of sugar that people typically consume – and that are considered safe by regulatory agencies – impair the health of mice."

The new placed groups of mice in room-sized pens nicknamed "mouse barns" with multiple nest boxes – a much more realistic environment than small cages, allowing the mice to compete more naturally for mates and desirable territories, and thereby revealing subtle toxic effects on their performance, Potts says.

"This is a sensitive test for health and vigor declines," he says, noting that in a previous study, he used the same test to show how inbreeding hurt the health of mice.

"One advantage of this assay is we get the same readout no matter if we are testing inbreeding or added sugar," Potts says. "The mice tell us the level of health degradation is almost identical" from added-sugar and from cousin-level inbreeding.

The study says the need for a sensitive toxicity test exists not only for components of our diet, but "is particularly strong for both pharmaceutical science, where 73 percent of drugs that pass preclinical trials fail due to safety concerns, and for toxicology, where shockingly few compounds receive critical or long-term toxicity testing."

The study was funded by the National Institutes of Health and the National Science Foundation.

A Mouse Diet Equal to What a Quarter of Americans Eat

The experimental diet in the study provided 25 percent of calories from added sugar – half fructose and half glucose – no matter how many calories the mice ate. Both high-fructose corn syrup and table sugar (sucrose) are half fructose and half glucose.

Potts says the National Research Council recommends that for people, no more than 25 percent of calories should be from "added sugar," which means "they don't count what's naturally in an apple, banana, potato or other nonprocessed food. … The dose we selected is consumed by 13 percent to 25 percent of Americans."

The diet fed to the mice with the 25 percent sugar-added diet is equivalent to the diet of a person who drinks three cans daily of sweetened soda pop "plus a perfectly healthy, no-sugar-added diet," Potts says.

Ruff notes that sugar consumption in the American diet has increased 50 percent since the 1970s, accompanied by a dramatic increase in metabolic diseases such as diabetes, obesity, fatty liver and cardiovascular disease.

The researchers used a mouse supply company that makes specialized diets for research. Chow for the mice was a highly nutritious wheat-corn-soybean mix with vitamins and minerals. For experimental mice, glucose and fructose amounting to 25 percent of calories was included in the chow. For control mice, corn starch was used as a carbohydrate in place of the added sugars.

University of Utah biology professor Wayne Potts, left, and former Ph.D. student James Ruff conducted a new study showing that sugar is toxic to mice in doses proportional to those now considered safe for humans -- the equivalent of a health human diet plus three sweetened soda drinks daily. They are standing in one of their "mouse barns," which were used for a new, sensitive toxicity test in which house mice compete for territory in a more natural environment than small cages. Credit: Lee J. Siegel, University of Utah.

House Mice Behaving Naturally

Mice often live in homes with people, so "mice happen to be an excellent mammal to model human dietary issues because they've been living on the same diet as we have ever since the agricultural revolution 10,000 years ago," Potts says.

Mice typically used in labs come from strains bred in captivity for decades. They lack the territoriality shown by wild mice. So the study used mice descended from wild house mice that were "outbred" to prevent inbreeding typical of lab mice.

"They are highly competitive over food, nesting sites and territories," he says. "This competition demands high performance from their bodies, so if there is a defect in any physiological systems, they tend to do more poorly during high competition."

So Potts' new test – named the Organismal Performance Assay, or OPA – uses mice "in a more natural ecological context" more likely to reveal of whatever is being tested, he says.

"When you look at a mouse in a cage, it's like trying to evaluate the performance of a car by turning it on in a garage," Ruff says. "If it doesn't turn on, you've got a problem. But just because it does turn on, doesn't mean you don't have a problem. To really test it, you take it out on the road."

A big room was divided into 11 "mouse barns" used for the . Six were used in the study. Each "barn" was a 377-square-foot enclosure ringed by 3-foot walls.

Each mouse barn was divided by wire mesh fencing into six sections or "territories," but the mice could climb easily over the mesh. Within each of the six sections was a nest box, a feeding station and drinking water.

Four of the six sections in each barn were "optimal," more desirable territories because the nest boxes were opaque plastic storage bins, which mice entered via 2-inch holes at the bottom. Each bin had four nesting cages in it, and an enclosed feeder.

The two other sections were "suboptimal" territories with open planter trays instead of enclosed bins. Female mice had to nest communally in the trays.

Running the Experiment

The mice in the experiment began with 156 "founders" that were bred in Potts' colony, weaned at four weeks, and then assigned either to the added-sugar diet or the control diet, with half the males and half the females on each diet.

The mice stayed in cages with siblings of the same sex (to prevent reproduction) for 26 weeks while they were fed these diets. Then the mice were placed in the mouse barns to live, compete with each other and breed for 32 more weeks. They all received the same added-sugar diet while in the mouse barns, so the study only tested for differences caused by the mice eating different diets for the previous 26 weeks.

The founder mice had implanted microchips, like those put in pets. Microchip readers were placed near the feeding stations to record which mice fed where and for how long. A male was considered dominant if he made more than 75 percent of the visits by males to a given feeding station. In reality, the dominant males made almost 100 percent of male visits to the feeder in the desirable territory they dominated.

With the 156 founder mice (58 male, 98 female), the researchers ran the experiment six times, with an average of 26 mice per experiment: eight to 10 males (competing for six territories, four desirable and two suboptimal) and 14 to 18 females.

The Findings: Added Sugar Impairs Mouse Lifespan and Reproduction

  • After 32 weeks in mouse , 35 percent of the females fed extra sugar died, twice the 17 percent death rate for female control mice. There was no difference in the 55 percent death among males who did and did not get added sugar. Ruff says males have much higher death rates than females in natural settings because they compete for territory, "but there's no relation to sugar."
  • Males on the added-sugar diet acquired and held 26 percent fewer territories than males on the control diet: control males occupied 47 percent of the territories while sugar-added mice controlled less than 36 percent. Male mice shared the remaining 17 percent of territories.
  • Males on the added-sugar diet produced 25 percent fewer offspring than control males, as determined by genetic analysis of the offspring. The sugar-added females had higher reproduction rates than controls initially – likely because the sugar gave them extra energy to handle the burden of pregnancy – but then had lower reproductive rates as the study progressed, partly because they had higher death rates linked to sugar.

The researchers studied another group of mice for metabolic changes. The only differences were minor: cholesterol was elevated in sugar-fed mice, and the ability to clear glucose from the blood was impaired in female sugar-fed mice. The study found no difference between mice on a regular diet and mice with the 25 percent sugar-added diet when it came to obesity, fasting insulin levels, fasting glucose or fasting triglycerides.

"Our test shows an adverse outcome from the added- diet that couldn't be detected by conventional tests," Potts says.

Human-made toxic substances in the environment potentially affect all of us, and more are continually discovered, Potts says.

"You have to ask why we didn't discover them 20 years ago," he adds. "The answer is that until now, we haven't had a functional, broad and sensitive test to screen the potential toxic substances that are being released into the environment or in our drugs or our food supply."

More information: Paper: dx.doi.org/10.1038/ncomms3245

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BobSage
1.6 / 5 (13) Aug 13, 2013
This one is going up on the company bulletin board. So many articles say x causes y but give no statistics. In this one the stats are overwhelming.
SolidRecovery
1.3 / 5 (13) Aug 13, 2013
Very thorough and conclusive study. I am digging the picture of the pens.
metingunduz
1.5 / 5 (8) Aug 13, 2013
Evolutionary wise most of the assumptions and conclusions derived with this experimenal study are absolutely `wrong` .. Let me explain why they are wrong ..
First every species (mouse , cat ,dog ,Homo Sapiens(humans) are all adapted to their `natural environment` and their `natural diet of course ..What does this mean is dogs carnivore diet is consist of meat and not honey which is located mostly higher up at the top of the tree or high places where the honey combs are ....So the analogy and assumptions are NOT VALID for the mouse (in this experiment) and we human beings ,because the natural environments and diet are different , it is absolutely absurd to assume mouse will ever find lots of `simple sugars` at its natural habitat , so mouse carbohydrate metabolism (Enzyme systems in other words genes(DNA) and their controls in addition to end organs (pancreas,liver,brain,kidneys,intestines ...name it ) using or handling(storage , metabolism etc..) from the characteristics and capacity of evolved receptors on the each different tissue cell membrane surfaces ARE COMPLETELY DIFFERENT FROM HUMAN ...This does not mean they can not handle sugar of course ...
So assumptions and analogical conclusions derived by comparing mostly `ground and underground living animal`with less excess to simple sugar type diet and human beings has more excess to simple sugars for their `natural diet` is absolutely wrong evolutionary wise . Human Beings CAN HANDLE large amount of simple sugars in their diet than mouse can , because it is `natural for human beings to excess abundant amount of simple sugar diet` over the course of millions of years evolution because of their natural environment .
So comparing APPLES with PEARS does not necessarily give correct conclusion and CAN NOT BE AN ACCURATE GUIDE or YARD STICK to follow ...Please get wise , do not start calculations based on `MOUSE simple sugar load diet` ...Its obviously too`toxic ` on these poor animals ...Human Beings (with well known exceptions of Diabetics and Pre Diabetics which is only 347 million people of World population) http://www.who.in...s312/en/ out of over whopping 7 Billion( with a B) which means only % 5 Diabetics of whole world population will have difficulty to handle it the other % 95 of world population will have no problem with it - few pre diabetics are exception- http://www.geohiv...now.aspx
can handle simple sugars easily simply they(human being as a primate species) evolved to consume it abundantly throughout their evolution as natural diet as sweet fruits with lots of simple sugars in it and even frequent consumption of honey throughout their millions of years of evolution . Obviously ground living mouse diet is primarily ` complex carbohydrates` rather than simple
sugars .

PS : Before even starting this experiment on these poor mice ; well planned researchers `could have compared` the `sugar load curves` pre and post prandial with normal Mouse and normal Human Beings so they could have gotten the idea of APPLE and the PEARL easily .....Fight against `Obesity` needs wiser and well educated approach based on metabolsim of Human Beings rather than targeted `shot gun approach` and scare tactics against `simple sugars` ...

Thank you
Dr.Metin Gunduz

Gmr
2.2 / 5 (10) Aug 14, 2013
Dr. Metin Gunduz
Refined sugar hasn't been part of the human diet for very long, so using the mouse model is not that far fetched. In both cases you have mammals that crave and process sugar in naturally available proportions exposed, now, to concentrations and volumes unheard of even a few hundred years ago.

The push of the sugar drink industry to supplant water and milk with soda has worked, to everyone's detriment. My own children balked when I insisted we have a glass of water in addition to whatever it was we drank at dinner (I insist on 100% juice if they have juice, or milk, and eschew soda whenever I can). But I distinctly remember myself drinking water with every meal as normal.

If anything, we see an industry eager to quickly quash research that shows its product is dangerous in profitable - er, I mean - large amounts. Cigarettes tried much the same thing for years, and the Koch brothers practice it in relation to climate research.
Gmr
1 / 5 (7) Aug 14, 2013
Oh, and phys.org? You've got a flaw in letter/word count in that if somebody right-click-pastes, as Dr. Metin Gunduz has above, they can get around the maximum character limit of a comment. This can be fixed by adding the "change" event to the letter/word count in addition to the keyup/keydown/keypress. As soon as focus is lost by the field, it would do a "final" word count and truncating, but this still won't stop it from pinging off the DB if somebody directly submits to the form destination. I'd suggest putting the same truncate/limiter on the server side - client is unreliable.
Jonseer
1 / 5 (10) Aug 14, 2013
Any study that starts out with factually incorrect data is false.

Sugar may be 50/50 glucose/fructose, but Americans don't consume sugar in their sodas or a host of other sweetened products.

Instead producers use High Fructose Corn Syrup which tests have demonstrated can range widely in make up despite its the stated 55/45 fructose/glucose balance when manufacturers are asked.

There have been reports that HFCS can regularly go up to 95% fructose/5% Glucose.

Such a a dramatic difference matters as the difference in how the body uses each is dramatic.

Yet despite this info being easily accessible, they don't know.

That in itself makes me think they have the typical anti-sugar agenda driven mind set that is only looking for ways to portray sugar as evil.

Of course calling sugar toxic.

Well if you drink too much water it's toxic too.

Physorg should be more wary of publishing articles that clearly have an agenda beyond the research they claim to be pursuing.
brianweymes
1 / 5 (3) Aug 15, 2013
Jonseer, does it matter a great deal? Is High Fructose Corn Syrup much better for you than other sugars?
DarkHorse66
1 / 5 (5) Aug 16, 2013
Jonseer, does it matter a great deal? Is High Fructose Corn Syrup much better for you than other sugars?

@brianw: Yes it does matter. But high fructose corn syrup is actually worse, because it is easier for the body to convert into fat-stores than most other sugars. Here are some links. The first three should should be okay to understand, but the last is bit more technical (you should still be able to get the general gist of it):
http://en.wikiped...rn_syrup
http://en.wikiped...d_health
http://www.thekit...e-112003
http://link.sprin...3#page-1
Happy Readings,
Cheers, DH66
Gmr
1.5 / 5 (8) Aug 16, 2013
Jonseer, the amount of sugar they fed the mice was hardly an LD 50 dose. It was a chronic moderate dose rather than a high acute dose. Something that would still probably fit in what a person might consider "normal" and not excessive consumption.

This serves to show that chronic low doses still might have deleterious effects, since highly refined and concentrated sugar is not a normal part of either creature's diet.
Sinister1811
1 / 5 (7) Aug 18, 2013
So they're using mice to tell us that sugar is toxic to humans? Why don't they tell us next that chocolate will kill us after seeing what it does to dogs? Mice and humans might be genetically similar but they aren't the same animal.
Judgeking
3 / 5 (2) Aug 18, 2013
Seems to be a real agenda with the lead scientist here, very biased. He's cutting refined sugar from his and his family's diet? No real scientist would apply test results to his life this quickly. He was finding the answer he wanted.
truthisoutthere
1 / 5 (6) Aug 18, 2013
With regards to vaccines. An increase in anti-bodies has NOTHING to do with immune system strengthening, it only means the body has been exposed to something. In my view vaccines are a good idea but they are just not compatible with the fine workings of the human body.
Bronwyn
not rated yet Aug 27, 2013
The land of denial and money....regarding sugar, that is. Remember when only kings and nobility had access to refined sugar? Remember how they always had the diseases that go along with it? We know cancer feeds on sugar, but why would someone as educated as a physician-who rarely is given a single class on nutrition-tell people to modify their diet? I could so go on and on and on...I think there are a few more of us out there...
Gmr
1 / 5 (7) Aug 29, 2013
" With regards to vaccines. An increase in anti-bodies has NOTHING to do with immune system strengthening, it only means the body has been exposed to something. In my view vaccines are a good idea but they are just not compatible with the fine workings of the human body. "


Nobody brought it up but you. Please take your antivaxxer spam and there is the door, we don't need any more thank you. We're up to our navels in mumps and measles instead.
Gmr
1 / 5 (7) Aug 29, 2013
"Seems to be a real agenda with the lead scientist here, very biased. He's cutting refined sugar from his and his family's diet? No real scientist would apply test results to his life this quickly. He was finding the answer he wanted."


Ah, the "No True Scotsman" argument again. Yes. Of course. It all makes sense. A Real scientist would wait a long time before taking an action that isn't actually harmful to possibly prevent harm.

Like seatbelts.