Tuesday, August 25, 2009

Low carbohydrate, high protein and ApoE-/- mice

OK, here's the hot abstract from back in 2007.

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.

Prompt reply from Dr Rosenzweig with the table of diet compostion, just asking now about the Ca modification and if it involves PO4 changes


Atticus said...

Science Daily is pretty crappy at linking the primary source. Found it after some digging


MarkD said...


Great comment - Not sure if this is in response to my email, but thanks anyway.


Thinking Aloud said...

Hi Peter

Funny that you commented on this idiot's paper today. My girlfriend forwarded me a bbc link to some mindless comments on this even more mindless study.

This is what I wrote to Anthony the author of this tripe. I have, as you know, no medical training whatsoever. You guys better back me up if he bothers to reply to me with more tripe.


Dear Anthony

Are you the Anthony who was interviewed for this article: http://news.bbc.co.uk/2/hi/health/8218780.stm ? If so, I would like to pose some questions to you if I may:

Which fats did you feed these mice ? We all know that PUFAs are bad for you.

Do you really believe a mutated mouse represents humans well enough to opine on nutrition for humanity ? Do you know that the function of cholesterol is ? Can you explain why all human centenarians have much higher cholesterol than people much younger than them ? Can you explain why we evolved to recycle cholesterol and not to excrete it ?

I suggest you read the work of Ron Rosedale (Interesting work of his) and some of Peter's work here http://high-fat-nutrition.blogspot.com/ before you continue to do humanity a disservice through blinkered medical research.

Most importantly, when you figure out how to bring my dead grandfather and grandmother back to life, who both followed advice like yours, let me know. Thank god I discovered the truth about the typical knowledge of people who think they are qualified to advise on diet before my mother fell to the same fate. She has followed Rosedale's eating plan at age 63 (since a health scare) and has regained vigor she has not known for the last 30 years. As has everyone else who has tried it. And it IS low carb.

Think carefully about the large numbers of lives your misinformation could ruin.

I will happily engage you in debate.


Stan Bleszynski said...

Dr. Rozenzweig decision seems to be a good illustration of Darwin at work! Eventually they will get out of our way. 8-:)

ItsTheWooo said...

If these undesired changes were not observed in WT mice (and only in the unnatural science-cultivated mutant), why would the dumbass doctor stop his LC diet? Derrr? Even if we ignore the fact mouse metabolism doesn't translate neatly to human metabolism, it simply CANT be ignored that a genetic freak mouse REALLY doesn't matter does it?

If dr did state this as a reason he stopped his LC diet, I doubt that any reasonable individual could be so easily persuaded (particularly someone familiar with science). I suspect years of fat-is-bad brainwashing made him so uncomfortable to begin and he was just looking for an excuse to bolt... sorta like kids exploring a "haunted house" who run screaming when they hear a creak.

Peter said...

Hi all,

There's an edit up about the full text.


Peter said...


It's possible to argue basing 45% of your diet on casein might not be a good idea. Sorry no reply on MCTs, stuff is busy at the mo!


pyker said...

More specifics on the diet contents are available in the "supplemental information", available for free download here. Shame on them for not putting these details into the study itself.

I'm not sure what to make of the huge increase in calcium salts in the LCHP diet, nor the large decrease in other minerals. Is that irrelevant?

Peter said...

Hi Pyker,

The Ca salt is probably important, especially if it is a phosphate. I have a paper on renal failure induced arterial calcification in mice from Malcolm Kendrick which has some possible bearing on this study. Might get time to blog on it soon.

I would also comment that no one just happens to measure EPC numbers without knowing that they matter. I find it inconceivable that they didn't know that they were going to drop the count, ie it is a set up study based on pilot where the protocol was optimised to produce the desired result.

I understand that EPC production is regulated by the kidneys and that casein based high phosphate diets accelerate renal failure. They do it far better than grain based diets.

Ordinary rat chow causes renal calcification within 13 weeks if you start them on it at 6 weeks of age. A high phosphate diet with 45% of calories from casein might well have done the same thing or worse within the time scale of this study.

I'll try and get a full post up on this some time soon.


Anonymous said...

"a low carbohydrate (‘low-carb’; 43% fat, 12% carbohydrate, 45% protein) diet"

obviously they weren't eating enough fat . . .

I'd sooner trust Jeff Volek


JohnN said...

It seems from the press release that the lead author has some personal bias against LC. Pehaps that explains the selection of ApoE mice and the decision to up the amount of protein.

This is one of the biggest FUD bomb (spreading fear,uncertainty and doubt) to hit the LC-community for quite a while. The personal annecdote angle can be extremely effective, disengeniously so, in disuading people from LC.

. said...

Excuse my being off-topic, but I want to ask what you think of coconut cream. I've done a search on your blog and you mention coconut oil a few times, but the only references to coconut milk/cream come from commenters.

I'm reasonably low-carb at the moment, but a bit bored and looking to expand my dietary choices.

What's sold in NZ as "coconut cream" is about the consistency of "whipping" cream, or engine oil (but tastier than the latter).

Is this a good food, d'ya think? Presumably if I drink coconut cream I get a bit of coconut oil with it (though perhaps not enough to be theraputic).

Here is the breakdown (goes without saying that I avoid the "lite" version):

Coconut Cream 52%
Water, Stabiliser (466)

Per 100ml
Energy ...... 1080kJ (285 Cal)
Protein ...... 1.3g
Fat, total .... 27.8g
-saturated .. 17.0g
Carbohydrate 1.6g
-sugars ....... 0.9g
Sodium ...... 15mg

. said...

Sorry, should have written per 100g (rather than 100ml)

Thackray said...


If that product was just coconut cream and water, the saturated fat content would be about 86 to 90% of the total fat. The fat numbers you list aren’t in that proportion. Maybe something else is added?

Here is a coconut cream product that I buy:
Note the % of saturated fat to total fat per serving.

Here is nutritional data on coconut oil:

Philip Thackray

Anonymous said...

Mark Sisson has a lot on coconut oil and etc.


I buy "creamed coconut" and stick it in curries and the like, Biona from Sri Lanka: carbs 20g/100, fats 68g of which saturated 59g, 6g protein, 14g fibre.

That'll do me, I'll probably have some tonight with a prawn curry

. said...

Thanks guys.

Few Northern hemisphere food products make it all the way down to NZ where I live, but I did find some coconut oil on line here. I've ordered a couple of jars so we'll see how it goes.

Peter said...

Hmm, the creamed coconut I get in the UK claims virtually zero carbs... Just went to check the label but found I've eaten it all!


Ellyah said...

Nice post about High protein and ApoE-/- mice

Anonymous said...

"Hmm, the creamed coconut I get in the UK claims virtually zero carbs... Just went to check the label but found I've eaten it all!

You too eh?

Yeah the carbs are mostly fibre, I guess it depends how you count them, or not. Good stuff either way . . .

. . . Michael Eades does a good takedown of this study also


Danyelle said...

Do you use coconut Peter? If so where do you get yours. Like the look of this:

Danyelle said...

Rather confused. Bought "pride" 200g block of creamed coconut. No nutrition info on it. Upon googling some coconut blakcs claim 6%,7% or 9.2%. (They include the fibre in that). A commenter on this post said theirs was 20% carbs. ALl this is too wild-a-difference to be fibre.
"Blue Dragon" brand claims to be only 1% carbs. So I have some coconut cream now but totally unsure of it's nutrition. I'm trying to lose on Atkins so really I was hoping it would be less than 5%.

Any ideas on who is right? Are there different processes in making these coconut blocks because I thought as long as the ingredients were 100% coconut the nutrition would be the same for these 200g blocks. What's going on?

Peter said...

Hi Danyelle,

This page


gives 6g sugars and 9g fibre per 100g of coconut flesh. Unless Blue Dragon are extracting the fibre in some way (which I doubt) these are probably the accurate figures. No idea how they do their labelling...


Danyelle said...

So we should assume 6% then. So I guess I ate 12g sugar when I ate a whole block (over many hours) yesterday.
No wonder I didn't get ketosis breathe then. LOL
But not the end of the world... if I ever stop trying to actually lose weight on Atkins and just want to maintain weight sounds like an ideal food.
It tastes kinda sweet so I knew it couldn't be zero.

Does the blue dragon taste sweet? I was on their website and they have a sensible figure for their "organic" creamed coconut block but the ridiculous figure for their normal non-organic block. Weird.

Unknown said...

Danyelle, I too have had this weird breath after eating a lot of coconut. I don't think it's a ketosis breath as I have been in ketosis and the breath isn't as it is when eating a lot of coconut. So It could be just the coconut.. or could it be related to candida ?