By Jerome Burne
Over the past year I have been wondering whether there is something deeply flawed about research into the effects of high fat diets on rats and mice, done presumably to clarify the effects on humans. The rodent work consistently tells us that high fat diets make you fat and diabetic, while research on humans finds they do the opposite. What is going on?
The forty-year-old standard advice warning us off saturated fat is looking increasingly dated, even though experts in some quarters – looking at you Diabetes UK– still cling to it. But the world of the lab rat seems to exist in a parallel universe or in a time warp when low fat high carbohydrate (LFHC) diet was widely believed to be the way to lose weight and stay healthy.
So are the results telling us that the increasingly popular low carb high fat approach is wrong? That after all there’s no need for official bodies to perform a major U-turn? Not as far as I can tell. In fact it seems the rodent work is highly misleading. Not only are the so called ‘high fat diets’ they are fed nothing like the low carbohydrate diets any informed human would follow, but the animals have been selectively bred to ensure they become fat and diabetic on a high fat diet. This is not research, it is a rigged game.
Low carbohydrate diet helps humans lose weight
The confusion this fake research is (intentionally?) generating can be seen by comparing a couple of recent results from human studies with a couple from the labs. Here is a randomised controlled study published in 2014 in the Annals of Internal Medicine and involved 148 healthy men and women, who had their weight and various health biomarkers measured over a year.
Half were on a standard low fat high carbs (LFHC) diet; the others were on a HFLC diet. The conclusion was that: ‘The low carbohydrate (HFLC) diet was more effective for weight loss and cardiovascular risk factor reduction.’
Around the same time Yale University put out a press release on a rodent study with the headline: ‘Mother’s high fat (HFLC) diet alters metabolism in offspring leading to higher obesity risk’.
There was no attempt to suggest that the reaction of rodents might be different to that of humans – a basic caveat with any animal research. The assumption is that what’s bad for mouse mums is bad for humans as well.
The study found the diet damaged a part of the mouse brain (hypothalamus) that controls basic functions like sex drive, appetite and the way energy is handled. As a result: ‘the offspring remained overweight and had abnormalities in glucose metabolism throughout life. ‘This is another way of saying they were fat and diabetic.
High fat diet damages human foetuses
The release then goes on unhesitatingly to declare that the human foetus would be harmed by high fat in the same way. ‘The findings suggest that the third trimester of pregnancy in humans is the most critical period,’ the release continues. What’s more, say the authors, by avoiding high fat meals and ‘altering their food intake’ (presumably returning to a low fat diet), ‘mothers can control or even reverse their offspring’s disposition to obesity.’
There are a number of high quality studies just in the last year that strongly suggest that high levels of fats are not a problem for humans. One was also published in the Annals of Internal Medicine – a review of 44 trials involving over 500,000 people, looking at how much fat they ate and how much fat they had in their blood.
The conclusion: ‘Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.’ A good and detailed summary of the saturated fat debate can be found in an article entitled ‘Don’t Blame Fat ‘in Time magazine, June 23 2014.
Meanwhile studies on the risks of high fat are still being pumped out from the parallel rodent world. Here’s one from October 2014 from the University of California, Berkeley, which found that drinking grapefruit juice could cut the amount of weight gain caused by feeding mice a high fat diet.
The mice were fed a diet that contained either 60% fat or 10% for 100 days. This pushed up their weight and their glucose levels; grapefruit juice reduced both. Grapefruit juice, the researchers concluded, might help to cut diabetes risk.
Rodent high fat studies deeply misleading
Grapefruit juice may or may not help obese and diabetic humans; a good way to find out would be to give it to humans in a trial. So why does fat has this effect on rodents and does it tell us anything useful about humans? It seems unlikely since it flies in the face of dozens of other studies (see example from HIUK post.)
In fact they are deeply misleading and not simply because humans are different to mice. Cancer, for instance, is easy to cure in rats and mice but, as researchers are well aware, the results usually fail to translate to humans. However nutrition researchers such as the ones at Yale don’t seem to think that is even worth mentioning.
I have no idea if a responsibly designed high fat diet eaten during a human pregnancy is more likely to predispose a child to diabetes and obesity than a low fat one with lots of glucose generating carbohydrates, but it seem unlikely.
It’s now clear that rodent research which is being used as the basis for advice about how best to feed our children and stay healthy has been done on lab animals fed a high fat diet that is virtually guaranteed to make them fat. What’s more there is a widely used strain that have been bred over generation from animals that naturally put on weight in response to fat.
Rodent high fat diet studies not to be used to advise humans
The first witness to support this serious charge is an article on the site of the University of California Davis Health System uploaded in 2008. This says that although rodent studies provide: ‘the foundation for much of the belief that high fat diets are detrimental to health,’ most aren’t properly designed: ‘so we can’t use the results to give people recommendations on diet’.
The article goes on to identify what’s wrong. It reveals that high fat diet often consists of 60% lard, 20% sugar and 20% milk protein, which it described as ‘the mouse equivalent of pork rinds, ribs and coke’. In the trials this combination is compared with a natural low fat vegetable based high fibre diet known as chow. The problem is that the trials ignore other elements in each diet that have direct health effects.
The UC Davis article is referring to a paper published in Cell Metabolism the previous year, which goes on to explain that rodent chow also contains lots of soy which has an oestrogen-like effect on how much food and water the animals want, how active they are and how much fat they store. Meanwhile the sugar in the high fat diet is linked to weight gain and insulin resistance. Combining high fat with sugar is what makes human junk food moreish and damaging.
This dubious mixture is then fed to animals that are unlike any found in nature as they have been selected for fat sensitivity; one widely used variant puts on weight and develops raised insulin even when being fed zero carbohydrates!
The rat that is specially designed to get fat on fat
Evidence for this comes from the second witness Richard Feinman Professor of Biochemistry at State University of New York Downstate Medical Center who is a long-term advocate of the benefits of the HFLC diet and has written about it for HealthInsightUK. He naturally wanted to find an explanation for the dramatically different effects the diet had on rodents and humans.
In a paper for Nutrition Metabolism in 2012, he goes into detail about this ‘zero carbs’ mouse, known as the C57BL/6 (also as B/6 or Black six ) strain. It is used in the vast majority of mouse experiments and has been selected specifically to put on weight and raise glucose in response to a high fat diet. The only way a regular rodent high fat study could produce a surprise result using B/6 would be for weight and glucose levels to drop.
In fact it is possible to feed them in such a way that doesn’t result in damaging diabetic symptoms but it is tricky and involves a delicate balance. In one study putting B/6’s on a diet made up of 95% fat, 5% protein (very low) and no carbohydrates at all, got the same beneficial results found in humans on very low carbohydrate diets. These include weight loss with no cut in calories, increased energy, improved glucose tolerance and reduced insulin.
However when Feinman ran a study keeping B/6s on very high fat, zero carbohydrates but raising the protein proportion to a more normal 20%, all the benefits were lost and the animals went back to weight gain plus a rise in glucose and insulin. So the idea that these animals can tell us anything about what happens to humans eating a nutritionally informed high fat diet is a gross distortion of the research.
Make high fat diets on rodents transparent
Remarkably, these seriously misleading high fat rodent studies are relied on as evidence for the dangers of fat by experts who should know better, such as Jeremy Pearson, vascular biologist and associate medical director at the British Heart Foundation. In an article in the magazine New Scientist in July last year entitled ‘The truth about saturated fat’ he defended the benefits of the low fat diet, commenting that the idea that a diet high in saturated fat raises the risk of heart disease: ‘remains persuasive’.
In support of this he pointed to the ‘hard evidence from studies in animals where the dietary control is possible to a degree it is not in people. They repeatedly show that high saturated fat leads to high LDL cholesterol and hardened arteries.’
I appreciate that I have combined a number of different things in this post – studies showing that high fat causes diabetes related problems; research showing that high fat doesn’t lead to heart disease. And that I’ve used fat and saturated fat interchangeably. But this is not a scientific paper. Its intention is to point up a serious and avoidable source of confusion in an area already rife with confusion and misinformation.
A useful start to correct it would be for all studies to make clear what the high fat diet actually consisted of and what strain of specially selected rodent was being used and what it had been selected for. Until then, before swallowing any rodent high fat result, season it with a large pinch of salt.
With special thanks to Peter Dobromylskyj a vet with physiology degree, who runs a very sophisticated academic blog on diet and health at http://high-fat-nutrition.blogspot.co.uk/ His comments were invaluable in sorting out various questions I had about animal research but any errors are mine.