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The cardiovascular complications of obesity have prompted interest in dietary interventions to reduce weight, including low-carbohydrate diets that are generally high in protein and fat. However, little is known about the long-term effects of these diets on vascular health. We examined the cardiovascular effects of a low-carbohydrate, high-protein diet (LCHP) in the ApoE−/− mouse model of atherosclerosis and in a model of ischemia-induced neovascularization. Mice on a LCHP were compared with mice maintained on either the standard chow diet (SC) or the Western diet (WD) which contains comparable fat and cholesterol to the LCHP. LCHP-fed mice developed more aortic atherosclerosis and had an impaired ability to generate new vessels in response to tissue ischemia. These changes were not explained by alterations in serum cholesterol, inflammatory mediators or infiltrates, or oxidative stress. The LCHP diet substantially reduced the number of bone marrow and peripheral blood endothelial progenitor cells (EPCs), a marker of vascular regenerative capacity. EPCs from mice on a LCHP diet also manifest lower levels of activated (phosphorylated) Akt, a serine-threonine kinase important in EPC mobilization, proliferation, and survival. Taken together, these data demonstrate that in animal models LCHP diets have adverse vascular effects not reflected in serum markers and that nonlipid macronutrients can modulate vascular progenitor cells and pathophysiology.
Researchers use mutant mice genetically engineered to be susceptible to heart disease to ‘prove’ carbohydrate restricted diets may harm arteries.
Defects in ApoE -/- result in defects in processing blood cholesterol.
As human studies continue to show the benefits of low carbohydrate diets and the general failure of low-fat diets, it is necessary for the nutritional establishment to find more and more obscure methods of attacking dietary carbohydrate restriction.
One method is to prepare mutant animal models, to use odd diets that humans would never consume, call them low carbohydrate diets and then show some deficit. Because mice are not generally susceptible to atherosclerosis, it was necessary for Foo and coworkers to use an ApoE-/- mutant and a ridiculously high protein diet to vilify low carbohydrate diets which have been a useful alternative for many people suffering from obesity, diabetes and metabolic syndrome.
In keeping with the traditions in scientific research, the authors do not cite the numerous studies showing benefit of low carbohydrate diets compared to the low fat diet that has been in place during the obesity and diabetes epidemic. That the NIH and other government agencies continue to fund this kind of biased research is probably a minor political problem in health care but should still be of concern to people who are confused about what their diet should be.
According to Dr. Richard D. Feinman, Biochemistry Professor at Downstate Medical Center in NY, “It is a mistake to consider one experiment in a mouse mutant over riding the scientific literature where similar research trials on actual human beings clearly show benefit of carbohydrate restriction for all markers of metabolic syndrome. For some reason these studies are not the ones picked up by the media. I suppose actual advances in science aren’t hot topics for headline news stories when it concerns the proven benefits of carbohydrate restriction.
Volek JS, Ballard KD, Silvestre R, Judelson DA, Quann EE, Forsythe CE, Fernandez ML, Kraemer WJ: Effects of dietary carbohydrate restriction vs low-fat diet on flow-mediated dilation. Metabolism 2009.
Volek JS, Phinney SD, Forsythe CE, Quann EE, Wood RJ, Puglisi MJ, Kraemer WJ, Bibus DM, Fernandez ML, Feinman RD: Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009, 44(4):297-309.
the scientifically correct title of this study should be ‘Vascular effects of a low-carbohydrate high-protein diet in ApoE mice’ because that is what it is about.
And here's the press release from 2009, I've put the text up on my odds and sods blog as press releases don't last for ever on the net. The paragraphs are a bit chewed up but you can get the gist OK.
Cardiologists are impatient people. If they want to study aortic aneurisms they tend to do things like placing a balloon in the aorta via the femoral artery, inflating it and then pulling. Down the aorta, with the balloon inflated. Or they might go in there surgically, cross clamp the aorta in two places, perfuse the isolated section of aorta with some unpleasant chemical, then set all back to normal and try out the latest drug for aneurism treatment on the preparation. The prime requirement is the suspension of disbelief that the "model" has anything to do with human senile dissecting aortic aneurisms. It doesn't.
Obviously the cholesterol fed Syrian hamster is a great model for arteriosclerosis, but it's boring. There's nothing sexy about feeding a herbivore cholesterol. Sexy needs genetically modified mammals to make it happen.
So you want a mouse to get atheroma? Well, they don't. Feed them mouse chow and they get arterial damage and fibrosis all right, but not nice big juicy cholesterol filled plaque. What to do? Delete a gene.
One offspring from the impatience of cardiologists is the apoE-/- mouse. This mouse is a genetic cripple who's ability to process fat has been severely damaged. There are a very, very, very small number of people in the world who are homozygous for defective apoE. They are functionally apoE-/-. Nature does not allow this commonly. Contrast it with FH where there are hundreds of different types of FH, ie breaking your LDL receptor gene is easily done and evolution has not attempted to conserve it particularly highly.
Feeding a high fat diet to apoE-/- mice is bad news for the mice. Until anyone gives us the full text of the paper we'll have no idea of exactly what they fed to the mice but, ultimately, they broke the mice first. Actually, if Dr Murray is anything to go by, even the full text won't tell us much about what they fed the mice!
If you are apoE -/- I wish you luck. Statistically, you're not. Neither is the cardiologist, Dr Rosenzweig, who gave up his LC diet on the basis of this study. But then, he thinks the transgenic apoE-/- mouse is a model for human arteriosclerosis.
EDIT: OK, I now have the full text (thanks H) and here is the total information supplied in the methods section about the diets:
"Male pups were placed on one of the three study diets 1 week after weaning: standard chow diet (Harlan Teklad #2018 rodent chow), high-fat ‘Western’ diet (Harlan Teklad # 88137) and a custom-ordered low-carbohydrate diet manufactured to our specifications (Harlan Teklad)."
That's it. It is traditional to give enough information in the methods section to allow another group to repeat your protocol. If the problems in these mice are NOT from being apoE-/- then Foo et all are to be congratulated on developing a diet to produce more problems than the Western or Cafeteria diet, but they ain't telling anyone how to do it! No answer from Murray on the same query.