Let Us Honor Ancel Keys, Our Patron, As We Cherry Pick Studies to Bash Fructose (Revised and Extended)
My apologies to anyone who received this in their RSS feed on Thursday as a teaser. I have now revised and extended it to include several studies showing that diet-induced obesity can be achieved in rats and mice without using any sugar at all, and have included a clearer conclusion.
Ancel Keys is best known in the assorted real food communities, or at least the assortment of real food communities friendly to dietary fat, for his infamous cherry picking.
Keys had presented data from six countries, purporting to show a clear linear relationship between the amount of fat consumed in a country and its incidence of heart disease. This graph is shown on the left below. The one problem was that data was available for 22 countries at the time, and including that data demolished the relationship. The “true” graph is shown below on the right.
December 22, 2011 Update: It would be more appropriate to say that including the data “greatly diminished” the relationship than that it “demolished” the relationship because the positive relationship still exists. See this excellent analysis by Denise Minger.
If we are going to criticize Keys for cherry picking, it behooves us to root out cherry picking from our own communities as well. This requires constant self-criticism, because bias is human nature, and anyone who isn't engaged in a devoted battle to overcome their own bias will be its prisoner. I myself cannot claim to always be victorious in this battle, but I do try.
I consider Dr. Robert Lustig an ally in the fight for real food. He makes as his primary enemies junk foods rich in refined sugar and high fructose corn syrup, and I agree these should be targeted as likely the most important causes of chronic disease. Dr. Lustig and many in the blogosphere, however, are circulating the claim that high-fat diets only induce obesity in laboratory animals if they are also high in sucrose. This simply isn't true.
Let's take a look at these diets.
About seven minutes into a recent interview on sugar and health, Dr. Lustig stated the following:
Those animal studies are very clear in terms of what's going on. If you wanna do diet-induced obesity, people say you put the rat on a high-fat diet. Garbage. Here's why. You can't get a rat to eat a high-fat diet, unless you add 20 percent sucrose to the diet. Basically what you're doing is you're giving them cookie dough. But if you give them lard, they won't eat it. They actually lose weight on that because that's the Atkins diet for them. It's not palatable, they don't like it, and they actually lose weight and their metabolic parameters improve. The only way to get an animal, rat, monkey, or any other animal for that matter, to eat a high-fat diet, is to lace the fat with sucrose. So the question is, which is doing the damage? The fat, or the sucrose in that case? And the answer is, both.
Research Diets marketed the first high-fat diet specifically designed and marketed to induce obesity in laboratory animals, and currently estimates that it ships enough high-fat diet to keep 50,000 mice worldwide on the march toward obesity at this very moment.
Nowadays, their 60% fat diet is most popular. Again, most of the fat comes from lard. The diet contains less than 7% of its calories from sucrose, which translates to about 3% of calories from fructose.
The diet also contains 13% maltodextrin, which is partially digested starch. The maltodextrin used in this diet averages ten glucose units per molecule, so can hardly be called a “sugar.” A “sugar” would contain one or two units per molecule. In any case, maltodextrin does not contain fructose.
As I pointed out in “They Did the Same Thing to the Lab Rats That They Did to Us,” the American Institute of Nutrition (AIN) recommended the inclusion of 13-15% maltodextrin broken down even further than this as well as 10% sucrose in order to reduce the amount of heat damage that would occur during the pelleting process. Thus this diet can hardly be said to be high in maltodextrin and it is pretty low in sugar.
Here's an example of a recent paper that used this 60% fat diet and compared it to the 10% fat, 35% sucrose control diet over the course of 8 weeks in mice:
Kirpich IA, Gobesjishvili LN, Bon Homme M, Waigel S, Cave M, Arteel G, Barve SS, McClain CJ, Deaciuc IV. Integrated hepatic transcriptome and proteome analysis of mice with high-fat diet-induced nonalcoholic fatty liver disease. J Nutr Biochem. 2011;22(1):38-45.
Compared to the mice eating the low-fat control diet relatively high in sucrose, the mice eating the high-fat, low-sucrose diet had 55% greater body weight and seven times as much body fat. The mice eating the high-fat diet developed fatty livers, whereas the mice eating the low-fat diet did not.
This all happened even though the mice eating the low-fat control diet were consuming over five times as much sucrose as the mice eating the high-fat diet.
More to the point, however, there are several studies available showing that high-fat diets can induce obesity in mice without any sugar at all.Here is what happens to two different strains of mice consuming high-fat or low-fat diets with or without sucrose for four months:
Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara AE, Opara EC, Kuhn CM, Rebuffe-Scrive M. Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism. 1995;44(5):645-51.
We can see the effect of fat if we compare the black and white bars to the patterned bars. Clearly, fat increased adiposity more than sugar in each strain of mouse, but the effects were much more pronounced in the strain of mouse shown on the right. The white bars represent a 58% fat diet that had no sucrose in it whatsoever. This diet clearly increased adiposity, especially in the susceptible strain.
Lest we be afraid the maltodextrin is the culprit, let's take a look at this study by the same authors:
After 16 weeks, fat increased adiposity in both strains (this time adjusted for body weight). The white bars represent the 58% fat diet that had no sugar. On top of this, none of the diets contained maltodextrin. Clearly high-fat diets can induce obesity in mice even without any sugar.
One interesting study showed that including sucrose instead of starch on a similarly high-fat diet can increase adiposity in rats by 23%. Unfortunately, this study did not include a low-fat control group so we can't really tell whether the sugar-free, high-fat diet induced obesity. Fortunately, however, the same authors performed a very similar study that compared starch to sucrose on a low-fat diet, which allows us to make a rough comparison:
The red and blue bars represent rats on diets that were 64% fat and 14% protein, with 21% carbohydrate as either starch or sugar. The green and purple bars represent rats on diets that were only 16% fat, 20% protein, and 54% carbohydrate as either starch or fat.
By comparing the blue and red bars, we see that a very high-fat diet produces 23 percent more adiposity in rats when it is accompanied by sucrose instead of starch. The sugar-free, high-fat diet shown in red, however, produced 74% more adiposity than the sugar-free, low-fat diet shown in purple. This would suggest that very high-fat diets produce adiposity in rats even when they do not contain any sugar at all. Or maltodextrin, for that matter.
Am I about to blame fat as the cause of obesity? Not in a million years.
There are a few reasons.
First, Research Diets boasts that they sell over 10,000 kilograms of their lard-based high-fat diet every month and that they have sold it to thousands of individuals at over 420 institutions in 33 countries. The company estimates that 50,000 mice are currently getting fat by eating it at this very moment.
What does this mean? It is well known that the response of rats and mice to these diets is highly variable. Two of the studies I cited above showed very large differences between strains of mice. Similar differences have been seen in rats, and in some strains of rats there is a very clear division between “susceptible” and “resistant” rats.As I pointed out in the “High-Fat Diets and Choline” section of my article, “The Sweet Truth About Liver and Egg Yolks — Choline Matters More to Fatty Liver Than Sugar, Alcohol, or Fat,” the first researchers who used high-fat diets to induce fatty liver noted that they could achieve this in some but not all strains of animals, and that they could achieve it during the winter but not the summer. This could, perhaps, also be true for obesity. This means there are likely to be genetic, environmental, and other factors that determine the success of the diet. If these factors confound rodent experiments, they would confound any generalization from rodents to humans to a much greater degree.
It also means that with the sheer quantity of people using this diet to induce obesity, there is plenty of room for failure to go unpublished.
In any case, fat or fructose may well operate very differently in whole foods than in purified diets. It is overall dietary patterns that produce health or disease, not isolated dietary components. This will relate to the overall nutrient-density of the diet, the diet's effect on satiety and the metabolic rate, and as Stephan Guyenet's new series is revealing, the effect of the foods within that diet on the reward centers of the brain. All of these effects are determined by interactions between different components.
As I pointed out in “Reductionism and Holism Go Hand in Hand,” looking at isolated components is important for understanding how things work, but if we don't re-synthesize the big picture our reductionism is pointless. Blaming fat because of its effect in these purified diets would be an example of “pulling a Campbell.”
There are many different factors that affect the ability of a high-fat diet to induce obesity in rodents and reviewing all of them is a gargantuan task for another day.
In any case, we can see quite clearly that fructose is not required for high-fat diets to induce obesity in rodents. While I do want to help steer our society away from junk foods full of refined sugar and high-fructose corn syrup (and fructose-free white flour!), I don't think that contriving fictitious myths about the effects of dietary fat on rodents is going to help us uncover the true causes of obesity.
That's not to say that you can't produce weight loss if you restrict carbohydrates to less than one percent and protein to less than ten percent. You can, as was done here. Although this is not because the rats won't eat the diet. But that's a topic for the next post.