Atherosclerosis, Glucorticoids & The Fried Lard Diet

Blatently stolen from Steven Guyenets blog.
He has already done the work for me and now the case is closed as far as SF goes, imho.


Monday, December 14, 2009
The Dirty Little Secret of the Diet-Heart Hypothesis
The diet-heart hypothesis is the idea that saturated fat, and in some versions cholesterol, raises blood cholesterol and contributes to the risk of having a heart attack. To test this hypothesis, scientists have been studying the relationship between saturated fat consumption and heart attack risk for more than half a century. To judge by the grave pronouncements of our most visible experts, you would think these studies had found an association between the two. It turns out, they haven't.

The fact is, the vast majority of high-quality observational studies have found no connection whatsoever between saturated fat consumption and heart attack risk. The scientific literature contains dozens of these studies, so let's narrow the field to prospective studies only, because they are considered the most reliable. In this study design, investigators find a group of initially healthy people, record information about them (in this case what they eat), and watch who gets sick over the years.

A Sampling of Unsupportive Studies

Here are references to ten high-impact prospective studies, spanning half a century, showing no association between saturated fat consumption and heart attack risk. Ignore the squirming about saturated-to-polyunsaturated ratios, Keys/Hegsted scores, etc. What we're concerned with is the straightforward question: do people who eat more saturated fat have more heart attacks? Many of these papers allow free access to the full text, so have a look for yourselves if you want:

A Longitudinal Study of Coronary Heart Disease. Circulation. 1963.

Diet and Heart: a Postscript. British Medical Journal. 1977. Saturated fat was unrelated to heart attack risk, but fiber was protective.

Dietary Intake and the Risk of Coronary Heart Disease in Japanese Men Living in Hawaii. American Journal of Clinical Nutrition. 1978.

Relationship of Dietary Intake to Subsequent Coronary Heart Disease Incidence: the Puerto Rico Heart Health Program. American Journal of Clinical Nutrition. 1980.

Diet, Serum Cholesterol, and Death From Coronary Heart Disease: The Western Electric Study. New England Journal of Medicine. 1981.

Diet and 20-year Mortality in Two Rural Population Groups of Middle-Aged Men in Italy. American Journal of Clinical Nutrition. 1989. Men who died of CHD ate significantly less saturated fat than men who didn't.

Diet and Incident Ischaemic Heart Disease: the Caerphilly Study. British Journal of Nutrition. 1993. They measured animal fat intake rather than saturated fat in this study.

Dietary Fat and Risk of Coronary Heart Disease in Men: Cohort Follow-up Study in the United States. British Medical Journal. 1996. This is the massive Physicians Health Study. Don't let the abstract fool you! Scroll down to table 2 and see for yourself that the association between saturated fat intake and heart attack risk disappears after adjustment for several factors including family history of heart attack, smoking and fiber intake. That's because, as in most modern studies, people who eat steak are also more likely to smoke, avoid vegetables, eat fast food, etc.

Dietary Fat Intake and the Risk of Coronary Heart Disease in Women. New England Journal of Medicine. 1997. From the massive Nurse's Health study. This one fooled me for a long time because the abstract is misleading. It claims that saturated fat was associated with heart attack risk. However, the association disappeared without a trace when they adjusted for monounsaturated and polyunsaturated fat intake. Have a look at table 3.

Dietary Fat Intake and Early Mortality Patterns-- Data from the Malmo Diet and Cancer Study. Journal of Internal Medicine. 2005.

I just listed 10 prospective studies published in top peer-reviewed journals that found no association between saturated fat and heart disease risk. This is less than half of the prospective studies that have come to the same conclusion, representing by far the majority of studies to date. If saturated fat is anywhere near as harmful as we're told, why are its effects essentially undetectable in the best studies we can muster?

Studies that Support the Diet-Heart Hypothesis

To be fair, there have been a few that have found an association between saturated fat consumption and heart attack risk. Here's a list of all four that I'm aware of, with comments:

Ten-year Incidence of Coronary Heart Disease in the Honolulu Heart Program: relationship to nutrient intake. American Journal of Epidemiology. 1984. "Men who developed coronary heart disease also had a higher mean intake of percentage of calories from protein, fat, saturated fatty acids, and polyunsaturated fatty acids than men who remained free of coronary heart disease." The difference in saturated fat intake between people who had heart attacks and those who didn't, although statistically significant, was minuscule.

Diet and 20-Year Mortality From Coronary Heart Disease: the Ireland-Boston Diet-Heart Study. New England Journal of Medicine. 1985. "Overall, these results tend to support the hypothesis that diet is related, albeit weakly, to the development of coronary heart disease."

Relationship Between Dietary Intake and Coronary Heart Disease Mortality: Lipid Research Clinics Prevalence Follow-up Study. Journal of Clinical Epidemiology. 1996. "...increasing percentages of energy intake as total fat (RR 1.04, 95% CI = 1.01 – 1.08), saturated fat (RR 1.11, CI = 1.04 – 1.18), and monounsaturated fat (RR 1.08, CI = 1.01 – 1.16) were significant risk factors for CHD mortality among 30 to 59 year olds... None of the dietary components were significantly associated with CHD mortality among those aged 60–79 years." Note that the associations were very small, also included monounsaturated fat (like in olive oil), and only applied to the age group with the lower risk of heart attack.

The Combination of High Fruit and Vegetable and Low Saturated Fat Intakes is More Protective Against Mortality in Aging Men than is Either Alone. Journal of Nutrition. 2005. Higher saturated fat intake was associated with a higher risk of heart attack; fiber was strongly protective.

The Review Papers

Over 25 high-quality studies conducted, and only 4 support the diet-heart hypothesis. If this substance is truly so fearsome, why don't people who eat more of it have more heart attacks? In case you're concerned that I'm cherry-picking studies that conform to my beliefs, here are links to review papers on the same data that have reached the same conclusion:

The Questionable Role of Saturated and Polyunsaturated Fatty Acids in Cardiovascular Disease. Journal of Clinical Epidemiology. 1998. Dr. Uffe Ravnskov systematically demolishes the diet-heart hypothesis simply by collecting all the relevant studies and summarizing their findings.

A Systematic Review of the Evidence Supporting a Causal Link Between Dietary Factors and Coronary Heart Disease. Archives of Internal Medicine. 2009. "Insufficient evidence (less than or equal to 2 criteria) of association is present for intake of supplementary vitamin E and ascorbic acid (vitamin C); saturated and polyunsaturated fatty acids; total fat; alpha-linolenic acid; meat; eggs; and milk" They analyzed prospective studies representing over 160,000 patients from 11 studies meeting their rigorous inclusion criteria, and found no association whatsoever between saturated fat consumption and heart attack risk.

Where's the Disconnect?

The first part of the diet-heart hypothesis states that dietary saturated fat raises the cholesterol/LDL concentration of the blood. This is held as established fact in the mainstream understanding of nutrition. The second part states that increased blood cholesterol/LDL increases the risk of having a heart attack. What part of this is incorrect?

There's definitely an association between blood cholesterol/LDL level and heart attack risk in certain populations, including Americans. MRFIT, among other studies, showed this definitively, although the lowest risk of all-cause mortality was at an average level of cholesterol. The association between blood cholesterol and heart attack risk does not apply to Japanese populations, as pointed out repeatedly by the erudite Dr. Harumi Okuyama. This seems to be generally true of groups that consume a lot of seafood.

So we're left with the first premise: that saturated fat increases blood cholesterol/LDL. This turns out to be largely a myth, based on a liberal interpretation of short-term feeding studies. In fact, it isn't even true in animal models of heart disease. In the 1950s, the most vigorous proponent of the diet-heart hypothesis, Dr. Ancel Keys, created a formula designed to predict changes in blood cholesterol based on the consumption of dietary saturated and polyunsaturated fats. This formula is extremely inaccurate and has gradually been dropped from the modern medical literature. Yet the idea that saturated fat consumption increases blood cholesterol/LDL lives on...

This is it, folks: the diet-heart hypothesis ends here. It's been kept afloat for decades by wishful thinking, puritan sensibilities and selective citation of the evidence. It's time to put it out of its misery.

Whole Health Source: Cardiovascular disease
 
Add to this all of the evidence on the proper omega 6/omega 3 ratio AND the evidence on excess sugar consumption in general and HFCS in particular and you have all you need to prevent most lifestyle diseases in this country.

As Dr Lustig said - the only liquids in your house should be water and milk (or in my case since I have an allergy to milk - coconut milk)

So - eliminate all fast food, all soft drinks, fruit juice, etc. - follow a paleolithic diet and you should, barring death by accident, die of old age!
 
Now you get the chance to go full circle. Not only are SFA's harmless, they may actually be protective because of their resistance to oxidation. Now, the "French paradox" isnt a paradox anymore. Their heart disease rate is significantly lower than ours and they eat lots of saturated fats. Their sugar consumption is a lot lower than ours too.
 
Add to this all of the evidence on the proper omega 6/omega 3 ratio AND the evidence on excess sugar consumption in general and HFCS in particular and you have all you need to prevent most lifestyle diseases in this country.

As Dr Lustig said - the only liquids in your house should be water and milk (or in my case since I have an allergy to milk - coconut milk)

So - eliminate all fast food, all soft drinks, fruit juice, etc. - follow a paleolithic diet and you should, barring death by accident, die of old age!

Now you get the chance to go full circle. Not only are SFA's harmless, they may actually be protective because of their resistance to oxidation. Now, the "French paradox" isnt a paradox anymore. Their heart disease rate is significantly lower than ours and they eat lots of saturated fats. Their sugar consumption is a lot lower than ours too.[/QUOTte]

Yep.
I think I can reject the FH Dx based upon the FH lipid vs control values used in this study:

http://www.annclinlabsci.org/cgi/reprint/32/1/50.pdf

and the fact that I have an older sister, 80yo now, who has led a spartan lifestyle and has escaped the vascular problems of my other sister and myself. Note also that our mother died at age 93 and also led a spartan lifestyle.
( at the time of the stroke(9/17/03):
tot chol=239
ldl=158
hdl=60
vldl=21
tg=106

So I think there is perhaps a, maybe, slight problem with the ldl receptor, if any, and various big problems with diet over the years.
But still I have a hard time rejecting all my feelings regarding animal fats and am considering vegetable sources instead.
Also a VAP is in order. This and much more study of the inflammatory processes is next.
Thanks
 
Now you get the chance to go full circle. Not only are SFA's harmless, they may actually be protective because of their resistance to oxidation. Now, the "French paradox" isnt a paradox anymore. Their heart disease rate is significantly lower than ours and they eat lots of saturated fats. Their sugar consumption is a lot lower than ours too.[/QUOTte]

Yep.
I think I can reject the FH Dx based upon the FH lipid vs control values used in this study:

http://www.annclinlabsci.org/cgi/reprint/32/1/50.pdf

and the fact that I have an older sister, 80yo now, who has led a spartan lifestyle and has escaped the vascular problems of my other sister and myself. Note also that our mother died at age 93 and also led a spartan lifestyle.
( at the time of the stroke(9/17/03):
tot chol=239
ldl=158
hdl=60
vldl=21
tg=106

So I think there is perhaps a, maybe, slight problem with the ldl receptor, if any, and various big problems with diet over the years.
But still I have a hard time rejecting all my feelings regarding animal fats and am considering vegetable sources instead.
Also a VAP is in order. This and much more study of the inflammatory processes is next.
Thanks

Consider this test as well

PLAC Test for Lp-PLA2 Identifies Heart Attack & Stroke Risk
 

Good lead

Lipoprotein-associated phospholipase A2: a potenti... [Curr Drug Targets Cardiovasc Haematol Disord. 2005] - PubMed result

http://www.springerlink.com/content/c7302xr261842170/fulltext.html (10.1007/s11883-009-0076-9)

It seems that ldl is back in the game:

Lp-PLA2, also known as platelet-activating factor (PAF) acetylhydrolase or type VIIA PLA2, belongs to the phospholipase A2 superfamily. Lp-PLA2 is produced by inflammatory cells involved in atherogenesis (macrophages and monocytes) and accumulates in human atherosclerotic lesions. It is now known that approximately 70% to 80% of Lp-PLA2 circulates bound to LDL and that the remainder is bound to high-density lipoprotein (HDL), lipoprotein(a), and some very low-density lipoproteins [8].

Also,

It now seems that darapladib’s effect is independent of cholesterol abundance, demonstrating an independent role for vascular inflammation in development of atherosclerotic disease, with Lp-PLA2 as the link between lipid metabolism and inflammation.

So, it might appear that the BASIC problem isnt cholesterol levels, as we suspected was the case, but a specific type of inflammation !
Now we are really back full circle- are glucorticoids more helpful than harmful?

AAARRRRHHHHGGG
 
Good lead

Lipoprotein-associated phospholipase A2: a potenti... [Curr Drug Targets Cardiovasc Haematol Disord. 2005] - PubMed result

http://www.springerlink.com/content/c7302xr261842170/fulltext.html (10.1007/s11883-009-0076-9)

It seems that ldl is back in the game:

Lp-PLA2, also known as platelet-activating factor (PAF) acetylhydrolase or type VIIA PLA2, belongs to the phospholipase A2 superfamily. Lp-PLA2 is produced by inflammatory cells involved in atherogenesis (macrophages and monocytes) and accumulates in human atherosclerotic lesions. It is now known that approximately 70% to 80% of Lp-PLA2 circulates bound to LDL and that the remainder is bound to high-density lipoprotein (HDL), lipoprotein(a), and some very low-density lipoproteins [8].

Also,

It now seems that darapladib’s effect is independent of cholesterol abundance, demonstrating an independent role for vascular inflammation in development of atherosclerotic disease, with Lp-PLA2 as the link between lipid metabolism and inflammation.

So, it might appear that the BASIC problem isnt cholesterol levels, as we suspected was the case, but a specific type of inflammation !
Now we are really back full circle- are glucorticoids more helpful than harmful?

AAARRRRHHHHGGG

Remember - getting the Omega6/Omega3 ratio will REDUCE inflamation

The western diet and lifestyle and diseases of civilization | Julianne's Paleo & Zone Nutrition Blog

Then download the full article

Also this - Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases -- Simopoulos 21 (6): 495 -- Journal of the American College of Nutrition

Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases

http://jcem.endojournals.org/cgi/reprint/91/2/398 (Polyunsaturated Fatty Acids, Inflammation, and Cardiovascular Disease: Time to Widen Our View of the Mechanisms -- Sacks and Campos 91 (2): 398 -- Journal of Clinical Endocrinology & Metabolism)

Polyunsaturated Fatty Acids, Inflammation, and Cardiovascular Disease: Time to Widen Our View of the Mechanisms

In conclusion, traditional paradigms for cardioprotective effects of omega-6 and omega-3 PUFAs tell an incomplete story of their multivalent potential. Linoleic acid, the principal omega-6 PUFA in the diet, and the omega-3 PUFAs are clearly beneficial as a result of shared mechanisms as in reduced inflammation, and distinct mechanisms as in serum
LDL cholesterol reduction by linoleic acid and triglycerides reduction by omega-3 PUFAs. A more complete understanding is needed of the role of arachidonic acid in atherosclerosis. Information is needed on the control of arachidonic acid levels in tissues by endogenous mechanisms as well as by dietary intake of its precursor, linoleic acid; on actions of
arachidonate-rich lipoproteins in cells; on the effects of arachidonic acid on vascular function and inflammation; and on the metabolic routing of arachidonic acid through proinflammatory vs. antiinflammatory pathways. Finally, the future holds promise to exploit genetic variation that controls the metabolic fate of dietary PUFAs and their potential benefit for CVD.
 
Saturated fat, carbohydrate, and cardiovascular disease: http://www.ajcn.org/content/91/3/502.full.pdf
 
Saturated fat, carbohydrate, and cardiovascular disease: http://www.ajcn.org/content/91/3/502.full.pdf

Good study, its a keeper. But I cant agree with substituting PUFA for SFA. PUFA is way too easily oxidized and enhances AGEs. INcreasing MUFA is better for simple carbs caloric substition and is the way I do it.
 
All of the people on the "Saturated Fats are OK & MIGHT be good for you" tend to forget (or don't know yet since its a novel concept) that saturated fatty acids activate toll like receptors and cause inflammation, whereas Omega-3 fatty acids seems to inhibit this. Just Google Scholar (or even simply Google) "toll like receptor saturated fat" and see what you come up with. As for now, the research article provided in a website link below provides a wonderful wealth of information regarding what is stated in this post.

Modulation of pattern recognition receptor-mediated inflammation and risk of chronic diseases by dietary fatty acids - Lee - 2009 - Nutrition Reviews - Wiley Online Library
 
All of the people on the "Saturated Fats are OK & MIGHT be good for you" tend to forget (or don't know yet since its a novel concept) that saturated fatty acids activate toll like receptors and cause inflammation, whereas Omega-3 fatty acids seems to inhibit this. Just Google Scholar (or even simply Google) "toll like receptor saturated fat" and see what you come up with. As for now, the research article provided in a website link below provides a wonderful wealth of information regarding what is stated in this post.

Modulation of pattern recognition receptor-mediated inflammation and risk of chronic diseases by dietary fatty acids - Lee - 2009 - Nutrition Reviews - Wiley Online Library


I personally welcome your input and am sure the others feel the same.
UnfortunatelyI can`t access the paper.
The ratio of omega3 vs 6 PUFA is certainly well documented in the literature as the main determinant of systemic inflammatory processes down to the cascade of chemical reactions involved. There are already many threads and posts investigating this effect in this forum.

We need to catalog them for reference, discussion and study.
 
I personally welcome your input and am sure the others feel the same.
UnfortunatelyI can`t access the paper.
The ratio of omega3 vs 6 PUFA is certainly well documented in the literature as the main determinant of systemic inflammatory processes down to the cascade of chemical reactions involved. There are already many threads and posts investigating this effect in this forum.

We need to catalog them for reference, discussion and study.

Sorry about that, see attachment for the review article, please.
 

Attachments

Sorry about that, see attachment for the review article, please.

"Therefore, the balance between different
dietary factors such as SFAs and PUFAs can be one of
the important determinants of the propensity for TLRmediated
inflammation and the subsequent development
of atherosclerosis"

That is the most interesting and extensive paper on the subject of inflammation and diet that I have ever read.
I have suspected that the SFA C-C chain length was important and not well understood.
But I wonder just how relavent these findings are in the real world. No mention was made of the
n-6 PUFA. Seems like a serious omission if trying to see the big picture. I have thought that MUFA is a good caloric replacement for simple carbs.
I am very interested in better understanding the role of the immune system in atherocslerosis. I wont lose track of this study. Do you know the date of publication? Got any more?
 
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"Therefore, the balance between different
dietary factors such as SFAs and PUFAs can be one of
the important determinants of the propensity for TLRmediated
inflammation and the subsequent development
of atherosclerosis"

That is the most interesting and extensive paper on the subject of inflammation and diet that I have ever read.
I have suspected that the SFA C-C chain length was important and not well understood.
But I wonder just how relavent these findings are in the real world. No mention was made of the
n-6 PUFA. Seems like a serious omission if trying to see the big picture. I have thought that MUFA is a good caloric replacement for simple carbs.
I am very interested in better understanding the role of the immune system in atherocslerosis. I wont lose track of this study. Do you know the date of publication? Got any more?

Year of publication date of the review article you just read is 2009.

I have included other peer-reviewed articles like you asked for via attachment form. All of them are from 2006 or later. TLR activation from SFA is a rather novel idea, with research probably only being around in the past 10 years or so discussing it.
 

Attachments

Year of publication date of the review article you just read is 2009.

I have included other peer-reviewed articles like you asked for via attachment form. All of them are from 2006 or later. TLR activation from SFA is a rather novel idea, with research probably only being around in the past 10 years or so discussing it.

Thanks! Get back to you after I read them. Wondering why you are interested in this subject?

You might find this lecture interesting:

[ame="http://www.youtube.com/watch?v=H_rPFF5X-pc"]YouTube - ?HDL: When Good Cholesterol Goes Bad?‏[/ame]
 
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ONY,
Enlighten me.

I can't find a good resource on this.

The inflammation I am referring to is the type of inflammation that is discussed in the articles I provided in my previous posts in this thread. Also Google or Google Scholar search "systemic inflammation" for more information on a type of low-grade inflammation that is associated with metabolic syndrome.
 
Do these studies isolate SFA as the ONLY variable that is causing the problem? In other words, what is the dietary context in which these studies were done where they see inflammation?
 
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