"new" link between diet and atherosclerosis

Cowboyjim · Oct 10, 2012

http://www.sciencedaily.com/releases/2012/10/121009131511.htm

Columbia University Medical Center (CUMC) researchers have found that a diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme associated with the development of atherosclerosis, and, conversely, that a diet high in omega-3 polyunsaturated fat lowers levels of this enzyme.

The findings establish a "new" link between diet and atherosclerosis and suggest a novel way to prevent cardiovascular heart disease. In addition, the research may help to explain why the type 2 diabetes drug rosiglitazone (Avandia) has been linked to heart problems.

these results need to be confirmed in human studies," said Dr. Deckelbaum. "The findings might also explain some of the cardiovascular benefits that have been attributed to omega-3 fatty acids."

"So we hypothesized that if rosiglitazone activates ppar-gamma, it might also activate EL, which would explain its effects on the heart."

In a similar vein (groan)
http://www.sciencedaily.com/releases/2012/10/121009112129.htm
Using these mice to study how disruption of PPAR-gamma leads to high blood pressure, the researchers uncovered a new biological pathway (called the Cullin-3 pathway) in blood vessels, which may be the key to the blood pressure-lowering effects of TZD drugs.
thiazolidinedione drugs (also known as TZDs), which are used to treat type 2 diabetes. These are highly effective in controlling blood glucose levels and have an added benefit of lowering blood pressure in some patients. However, TZDs cause unrelated but potentially severe side effects in some patients

Osidge · Oct 13, 2012

Hi all

This may be of interest to those following a low carb/high fat diet - although not yet confirmed in humans.

Regards

Doug

borofergie · Oct 13, 2012

Might be interesting to rats eating a low-carb diet...

Actually, since the rats weren't eating a low-carb diet, it's not even relevant to low-carb rats, it certainly isn't relevant to low-carb humans.

The key thing about a low-carb diet is that it has to be low in carbohydrate. Adding extra fat to a high-carbohydrate diet is much more relevant to people eating a regular "balanced" diet.

IanD · Oct 13, 2012

From the study cited:

In the current study, a strain of mice susceptible to atherosclerosis was fed a normal diet enriched with either palmitic acid (a common saturated fat) or eicosapentaenoic acid (an omega-3 fatty acid,

It is well-known that palmitic acid causes problems, but that these problems do NOT occur with the naturally occurring saturated fats such as butter containing also linolenic acid.

I followed this up with a researcher who did the same sort of research with cells & with rats. In reply he recommended a low carb/low fat diet (I must ask him where we get our energy from - protein? but he's a specialist in diabetes related kidney disease) but concluded:

please keep spreading the toast with butter (but maybe not too thickly and certainly not to excess). There is no real problem with a healthy intake of saturated fatty acids - infact they are good for you at reasonable amounts. However, someone eating 20 slices of buttered toast a day may be putting themsleves at risk!

Palmitic acid is NOT a fat. It is component of saturated fats. This sort of research will go on, & produce results that will "prove" animal fats are bad. Why did they not feed the mice on added cheese - 1/3 fat ?

I will resurrect & link the thread where I reported on this.

IanD · Oct 13, 2012

I wrote:

I was very interested in your presentation at Hounslow last Tuesday, particularly because my Dr s monitoring my kidney function. My eGFR has been around 60 for several years, while my wife's is around 55. My wife's brother had a transplant 21 years ago.

Your work with EK on "Alpha-Linolenic acid protects renal cells against palmitic acid lipotoxicity via inhibition of endoplasmic reticulum stress" was of particular concern - my low carb diet includes significant amounts of animal fats. I also eat nuts & use olive oil in my cooking. I could only access the title of your papers.

I did a google search for palmitic acid & found "Palmitic acid: the horror never ends"
http://high-fat-nutrition.blogspot.com/2011/04/palmitic-acid-horror-never-ends.html
Quote: "Oleate alone did not cause mtROS generation and mtDNA damage, and its addition to palmitate prevented palmitate-induced mtDNA damage, increased total ATP levels and cell viability, and prevented palmitate-induced apoptosis and inhibition of insulin-stimulated Akt (Ser(473)) phosphorylation." That confirms Elias findings using a-linolenic acid.

That referred me to: "A low-carbohydrate diet may prevent end-stage renal failure in type 2 diabetes. A case report." http://www.ncbi.nlm.nih.gov/pubmed/16774676
Quote: "An obese patient with type 2 diabetes whose diet was changed from the recommended high-carbohydrate, low-fat type to a low-carbohydrate diet showed a significant reduction in bodyweight, improved glycemic control and a reversal of a six year long decline of renal function."

These studies indicate that while palmitic acid alone is harmful, in it's natural combination in fatty foods any harmful effect is neutralised, while, as part of a low carb diet, fatty foods enhance health.

You will appreciate that there is on-going concern about fats in our diet & I would appreciate your comments.

He replied:

I'm glad you enjoyed my talk in Hounslow last month and that it literally gave you food for thought. As requested, I have attached a PDF copy of Elias's paper which was published in the European Journal of Pharmacology back in 2009 and which I based a lot of my talk on.

As you have mentioned, this study confirmed the findings of other studies that linolenic acid (an unsaturated fatty acid) was able to provide good protection against the renal lipotoxic effects of palmitic acid - a saturated fatty acid and is a component of animal and milk fats. This confirmed the findings of Noel Morgan's group at Peninsula Med School who looked have observed a similar effect on pancreatic beta cells.

I would certainly agree that a low carbohydrate diet can be beneficial especally when it is combined with a reasonably low fat diet which is supplemented by an good intake of unsaturated fatty acids as in your current diet which includes nuts (a good source of unsatuareted fatty acids).

However, my concern is that some people are reducing their carbohydrate intake (which is beneficial) but still have a relatively high intake of saturated fatty acids in thier diet. I would suggest that this puts considerable strain on renal (and other) cells and increase the chances of developing diabetic nephropathy and other complications. This risk may be increased could be reduced by an increased intake of unsaturated fatty acids. However, the best way to reduce the risk would be for these people to reduce their saturated fatty acid intake overall.

So my overall advice would be that moderation with regards to sataurated fatty acid intake would be best regardless of carbohydrate intake (which has its own benefits) - so please keep spreading the toast with butter (but maybe not too thickly and certainly not to excess). There is no real problem with a healthy intake of saturated fatty acids - infact they are good for you at reasonable amounts. However, someone eating 20 slices of buttered toast a day may be putting themsleves at risk!

He's coming to Hounslow again soon - I must prepare my questions .....

borofergie · Oct 13, 2012

IanD said:
I would certainly agree that a low carbohydrate diet can be beneficial especally when it is combined with a reasonably low fat diet

That's one of the funniest things that I've ever read. So basically a kidney expert recommending a very high protein diet.

Let me know if he comes to Hounslow, I'd love to have a little "chat" with him.

IanD · Oct 13, 2012

borofergie said:
IanD said:

I would certainly agree that a low carbohydrate diet can be beneficial especally when it is combined with a reasonably low fat diet

Click to expand...

That's one of the funniest things that I've ever read. So basically a kidney expert recommending a very high protein diet.

Let me know if he comes to Hounslow, I'd love to have a little "chat" with him.

Tuesday Nov. 27 - from 7 p.m.

borofergie · Oct 13, 2012

Cowboyjim said:
Columbia University Medical Center (CUMC) researchers have found that a diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme associated with the development of atherosclerosis, and, conversely, that a diet high in omega-3 polyunsaturated fat lowers levels of this enzyme.

If this were true in humans, how is it that no-one has ever been able to link saturated fat intake with increased mortality?

Why bother killing rats to try and find a mechanism for an effect that is not observed clinically?

IanD · Oct 13, 2012

borofergie said:
Cowboyjim said:

Columbia University Medical Center (CUMC) researchers have found that a diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme associated with the development of atherosclerosis, and, conversely, that a diet high in omega-3 polyunsaturated fat lowers levels of this enzyme.

Click to expand...

If this were true in humans, how is it that no-one has ever been able to link saturated fat intake with increased mortality?

Why bother killing rats to try and find a mechanism for an effect that is not observed clinically?

They haven't "found that a diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme associated with the development of atherosclerosis, " but a diet rich in palmitic acid. Palmitic acid is a fatty acid component of fats, but is not a fat. Presumably if they use butter & cheese, they do not get the harmful effects, so they use a component known to be harmful to produce harm in their tests. That is dishonest.

Patch · Oct 15, 2012

The "Study" said:
However, someone eating 20 slices of DRY toast a day WILL be putting themsleves at risk!

Fixed that for ya...

phoenix · Oct 15, 2012

T

hey haven't "found that a diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme associated with the development of atherosclerosis, " but a diet rich in palmitic acid. Palmitic acid is a fatty acid component of fats, but is not a fat. Presumably if they use butter & cheese, they do not get the harmful effects, so they use a component known to be harmful to produce harm in their tests. That is dishonest

Dishonest?
All the details are in on line supplements
They used mouse chow containing 19% fat: either 91% fish oil+ 9% corn oil (high omega 3 ) or 78% coconut oil + 13% olive + 9% corn oil (high in palmitic acid) both experimental diets contained the same amount of fat.(19%) There was a control group eating 5% fat mouse chow.
Palmitic acid is a SFA that is contained in varying proportions in most fats and oils.( almost a third of the fatty acid contained in butter is palmitic acid . In this experiment cholesterol amounts were kept consistent at 0.2%, I would suggest that using butter( very high in cholesterol) would have confounded the experiment.
If the coconut oil was partially hydrogenated, then that would also confound the results.However I would think they would be fully aware of the effect of trans fats.(well I am and I'm not a specialist ) They do give full details of the source of the chow which could be followed up .

I agree that results in animal models aren't always replicated in humans. Good summary of the pros and cons , and value in lipid research
http://www.dtu.dk/upload/centre/food-dt ... eminar.pdf

Butter and cheese might indeed give different results since they contain high levels of different fats and it may also be that it depends on the foods that they are combined with. (patterns of eating ie diet)
How about beef + dairy and beef + olive oil eaten by humans ? (or as Ron Krauss puts it, a cheeseburger v hamburger dressed in olive oil)
http://www.meandmydiabetes.com/2012/04/ ... t-depends/
The paper is behind a pay wall but there is a presentation of the results here:
http://www.slideshare.net/pronutritioni ... -carb-diet

IanD · Oct 15, 2012

phoenix said:
Ian said:

They haven't "found that a diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme associated with the development of atherosclerosis, " but a diet rich in palmitic acid. Palmitic acid is a fatty acid component of fats, but is not a fat. Presumably if they use butter & cheese, they do not get the harmful effects, so they use a component known to be harmful to produce harm in their tests. That is dishonest

Click to expand...

Dishonest?
All the details are in on line supplements
They used mouse chow containing 19% fat: either 91% fish oil+ 9% corn oil (high omega 3 ) or 78% coconut oil + 13% olive + 9% corn oil (high in palmitic acid) both experimental diets contained the same amount of fat.(19%) There was a control group eating 5% fat mouse chow.
Palmitic acid is a SFA that is contained in varying proportions in most fats and oils.( almost a third of the fatty acid contained in butter is palmitic acid . In this experiment cholesterol amounts were kept consistent at 0.2%, I would suggest that using butter( very high in cholesterol) would have confounded the experiment.
If the coconut oil was partially hydrogenated, then that would also confound the results.However I would think they would be fully aware of the effect of trans fats.(well I am and I'm not a specialist ) They do give full details of the source of the chow which could be followed up .

I agree that results in animal models aren't always replicated in humans. Good summary of the pros and cons , and value in lipid research
http://www.dtu.dk/upload/centre/food-dt ... eminar.pdf

Butter and cheese might indeed give different results since they contain high levels of different fats and it may also be that it depends on the foods that they are combined with. (patterns of eating ie diet)
How about beef + dairy and beef + olive oil eaten by humans ? (or as Ron Krauss puts it, a cheeseburger v hamburger dressed in olive oil)
http://www.meandmydiabetes.com/2012/04/ ... t-depends/
The paper is behind a pay wall but there is a presentation of the results here:
http://www.slideshare.net/pronutritioni ... -carb-diet

Phoenix - You didn't give a link to your source of info on the OP summary.

You say: "They used mouse chow containing 19% fat: either 91% fish oil+ 9% corn oil (high omega 3 ) or 78% coconut oil + 13% olive + 9% corn oil (high in palmitic acid) both experimental diets contained the same amount of fat.(19%) There was a control group eating 5% fat mouse chow." NOT according to the released data. You appear to be reporting a completely different study.

Coconut oil is generally accepted as containg "good" sat fats, with only around 7-10% palmitic acid - the one they use in experiments (including the one cited) to "prove" that sat fats are bad.

I reported correspondence with a professor who spoke to our support group. He did not disagree with what I had found about palmitic acid.

borofergie · Oct 15, 2012

20% fat, I'm guessing maybe 20% protein, which would leave 60% carbohydrate.

No two ways about it 20:20:60 is a low fat, high carb diet.

Good overview of research linking saturated fat to blood cholesterol levels in humans:
http://wholehealthsource.blogspot.com/2 ... rease.html
(there is none).

Since there is no research that links saturated fat consumption to either blood cholesterol or increased heart attack risk, they are having to dig deeper and deeper to try and justify their irrational hatred of saturated fats. It's laughable.

Osidge · Oct 15, 2012

This link reviews a recent meta analysis: http://m.ajcn.nutrition.org/content/92/2/459.2.short

At the end of the day, as with much in health, there is information out there and we have to make the best choices for our future health taking into account as much, or as little, of it as we choose. We will know at some stage whether we made the right or the wrong decisions.

Regards

Doug

phoenix · Oct 15, 2012

They don't actually claim that the diet they fed to the mice was high in palmitic acid. I made that assumption without thinking/reading carefully , sorry. (you did say that they were using a diet high in palmitic acid so I decided to look up the diet; these diets are usually listed as addenda to the full paper)
The mouse study part of it isn't said to be high in palmitic acid . It was, as they say, high in sat fat, (coconut oil has 85% sat fat It would be high in lauric acid.
They don't give the exact proportions of the diet; you could find the manufacturers site and look it up.
http://atvb.ahajournals.org/content/ear ... 8.abstract
check out the data supplements (DS 2)
The palimitic acid part of the experiment was a cell culture but I don't really understand your differentiation between the fatty acid and fat. Fatty acids will exist in the body either bound up as part of a triglyceride or in the cell as free fatty acids. (as I think is happening in the experiment here; though TBH I think that we'd have to be specialist biochemists to understand the detail of that part of the research)

Stephen have you read the interview with Krauss?
This postdates Stephan's article and yes is a short term feeding trial but it may explain some of the findings in longer term studies on red meat (I'd always though it was probably the processed meat that it's always lumped with)
Stephan's recent paper on Dairy fat is also later and in this he says

The evidence on cardiovascular disease is inconsistent, with a number of studies suggesting a protective association, a few suggesting a harmful one, and several suggesting no association

His caveats are also worth reading
http://wholehealthsource.blogspot.fr/20 ... -high.html

borofergie · Oct 15, 2012

Osidge said:
This link reviews a recent meta analysis: http://m.ajcn.nutrition.org/content/92/2/459.2.short

For the avoidance of doubt, the conculsion of the meta-analysis you link to is: "A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat. "

This backs up my point. No-one can (ever) say that there is zero risk, but since no-one has been able to demonstrate that saturated fat increases cholesterol or heart disease, you'd have to conclude that the influence is either zero, or too small to measure in experiments.

Be in no doubt, there is zero credible scientific evidence to back up the NHS's high-carb/low-fat dietary guidelines.

Osidge · Oct 15, 2012

I am happy to accept the fact that some fats are better than others for our health and will base my health decisions on that acceptance. If I am wrong then that will be my downfall. Incidentally, my partner, who has a rare blood cancer, is following the same path on the advice of a respected haematologist to avoid comorbidities.

Keep well

Doug

borofergie · Oct 15, 2012

phoenix said:
Stephen have you read the interview with Krauss?
This postdates Stephan's article and yes is a short term feeding trial but it may explain some of the findings in longer term studies on red meat (I'd always though it was probably the processed meat that it's always lumped with)
Stephan's recent paper on Dairy fat is also later and in this he says

The evidence on cardiovascular disease is inconsistent, with a number of studies suggesting a protective association, a few suggesting a harmful one, and several suggesting no association

Click to expand...

His caveats are also worth reading
http://wholehealthsource.blogspot.fr/20 ... -high.html

Thanks Phoenix, both great links, I enjoyed them both. I think that it would be fair to say that neither Guyenet or Krauss are of the opinion that saturated fat is directly responsible for cardiovascular disease. It would also be fair to suggest that both would agree that carbohydrate intake plays a much stronger role in determing cardiovascular outcomes than saturated fat.

From a Paleo position both are very interesting, because strict Paleo rejects dairy as a neolithic foodstuff (although in I'm sure most adherents indulge to some extent), and it seems that dairy is the factor at play. If it did turn out that dairy is a neolithic agent of disease, I think that it woud be another excellent validation of paleo / evolutionary diet principle.

As I said above, if the was a strong association between saturated fat on CVD and / or cholesterol, it would be apparent from the literature. If there is any influence at all, it is probably so small as to be insignificant. From an evolutionary viewpoint, it is quite difficult to see that it could be negative at all.

We need to remember that the only reason that saturated fat was ever demonised in the first place, is that it was required as a crutch to make the whole Keys Diet-Heart hypothesis work. It's fair to say since that hypothesis is now in tatters, that it's time to give poor old sat-fat a long awaited reprieve.

borofergie · Oct 16, 2012

Been thinking a lot about this last night. Are we really at the stage that the only way that we can implicate saturated fat in the "diet heart hypothesis" is to feed subjects a diet that consists entirely of beef covered in cheese?

Not even I eat beef, for breakfast, lunch and dinner.

Seriously, where is the data? How many diabetics are going to die because of a false insistance on low-fat and/or PUFA rich diets?

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