Robb Wolf: On Palmitic Acid, Carbs, LDL and CVD
Palmitic acid is 16 carbons long, fully saturated, and commonly found in palm oil and animal products, including beef, eggs, milk, poultry, and seafood. Palmitic acid has long been implicated in CVD, as it tends to raise LDL cholesterol. Among the saturated fats, it would appear palmitic acid does pose the greatest likelihood of increasing LDL cholesterol. However, palmitic acid has also recently been shown to be vital both to forming new memories and accessing long-held memories. As we shall see when we investigate how our diet has changed, a Paleo diet supplies an adequate amount of palmitic acid for optimum cognitive function while limiting the intake to levels that are not harmful to the cardiovascular system. It is also important to note that excessive carbohydrate intake leads to palmitic acid production. If you recall from the insulin chapter, when liver glycogen is full, additional carbohydrate is converted to palmitic acid. This process appears to blunt our sensitivity to leptin, which then inhibits our satiety to a normal meal. This is the beginning of insulin resistance and is at the heart of the mechanism of how we cease to respond to food by feeling "full."
From The Paleo Solution by Robb Wolf 2010, p. 108.
Point-by-Point Comments
- Palmitic acid content of various animal products varies widely. See my Fatty Acid Contents posts.
- A citation for the role of palmitic acid in memory would be nice here. I personally have observed that cognitive function of those from cultures historically consuming low fat primarily seafood based diets does not seem to be impaired. And no that's not a stereotype, it's first hand knowledge, given my majors/fields, having studied and worked with many Asian students.
- What is the evidence that "a Paleolithic diet" supplies just the right amount of palmitic acid? Given the wide variety of "paleo" diets, even those that could be constructed within the guidelines Robb sets out in the book.
- Do we even know what this proper balance is? Is there any research on minimum levels for cognitive function and/or maximum levels above which cardiovascular function and leptin sensing are impaired?
- If palmitic acid is required for good cognitive function, why would de novo lipogenesis of "excess" carbs be necessarily a bad thing? I've somewhat jokingly addressed this before: There's no dietary need for saturated fat ... . One point made in that post would seem to go against the notion of a palmitic acid requirement for proper cognitive function, that being that DNL is only upregulated in times of excess, not scarcity. One might make the case that since we evolved to consume large amounts in the diet no endogenous source is required, but then why wouldn't we have evolved to manufacture EPA and DHA from excesses?
- Even in gross excesses, palmitic acid produced by the liver is on the order of a few grams per day (see here and here). If palmitic acid blunts leptin sensitivity, then dietary intake would far exceed DNL and blunt leptin sensitivity long before we get to excess carb contributing its piddly amount. So ... if palmitic acid manufactured from excess carbs are detrimental, why aren't larger quantities obtained directly from the diet even moreso?
- Leptin is not a postprandial satiety hormone. If it were, it would indeed need to "spike" after meals, counter to claims made by some. Then impaired leptin sensitivity would be a plausible route to reduced satiety. But if anything leptin is depressed slightly after a "normal" mixed meal.
- The last statement, "This is the beginning of
insulin resistance and is at the heart of the mechanism of how we cease
to respond to food by feeling 'full'." is a huge stretch. Stated as definitively yet vaguely as it was, I consider irresponsible. Robb was careful to use the qualifier "appears to" with regards to leptin sensitivity. At the very least a "may be" in plase of "is" is in order in that statement. But going from leptin sensitivity to insulin resistance and impaired satiety signalling in basically one sentence? This is the sort of thing readers pick up on, perhaps hear someone else say similar, and before long it becomes "fact" and "common knowledge", repeated more and more and nobody questions where the concept came from.
Comments
I ask again - most people on the paleo diet report that their LDL-C levels INCREASE on a paleo diet yet are told to IGNORE this since their pattern size usually changes to large and buoyant.
This I don not understand.
See: Pruitt, Garcia & Holbrook, Regulation of Psyrohic Histamines Through The Process Of Palmitosis, Journal of Scientific Things Involving Dietary Stuff, Issue 8, pp. 83-122 (1997)
Taubes, for instance, was clearly reticent to have his cholesterol tested on Oz for this very reason.
"Keep in mind as you go through these that I do indeed eat three eggs with cheese, bacon and sausage for breakfast every morning, typically a couple of cheeseburgers (no bun) or a roast chicken for lunch, and more often than not, a ribeye or New York steak (grass fed) for dinner, usually in the neighborhood of a pound of meat. I cook with butter and, occasionally, olive oil (the sausages). My snacks run to cheese and almonds. So lots of fat and saturated fat and very little carbohydrates. A deadly diet, according to Dr. Oz. Without further ado, here are my numbers"
http://garytaubes.com/2011/04/before-sugar-were-talking-about-cholesterol/
TC - 204
Trigs - 64
HDL - 68
LDL - 116
To a family doctor? To a hospital affiliated walk-in clinic? To a respectable physician he knows?
Nope. Taubes gets his order from an out of state diet doctor who is a psychiatrist by training, prescribes appetite suppressants along with a VLC diet, encourages eating as little as possible, claims Atkins doesn't work, etc.
Nothing out of the ordinary there?
Does the man have no sense? Amazing what some won't question in the throes of blind hero worship.
Gary says what he eats daily in his blog post. It IS VLC. Darned near zero carbs. He is flirting with acidosis - that's what the Na, Cl, BUN and CO2 levels are indicative of. Not critical, but there's a trend there, and possibly showing early signs of kidney dysfunction or heading in that direction.
So in need of a little rehabilitating from his appearance, Gary's wife suggests he get his cholesterol tested. Does he decide that it might be a good idea to have a personal physician where he has now lived for around a year? No. He takes the "easy way" out and calls up his friend, bariatric physician Bill Nagler.
Let's be real here folks, if Dr. Oz were friends with Nagler or Joel Fuhrman went this route with a doctor friend, who had a weight loss business pushing injections and pills with a vegetarianish high carb twist, and also claimed Joel's diet didn't work, they would be roundly and rightly criticized for it. But no. Such is the hero worship of Gary Taubes that he can associate himself with such a shady quack of a character and it's the fact that anyone points this out that's at issue. Taubes should have taken Hans Keer's advice and quit while he was behind.
http://www.billnagler.com/
Going on Oz he had to know this would be an issue. Did he really think Oz wasn't going to mention cholesterol? Testing was mentioned backstage before the taping. Fair or not for Oz to "sand bag" him specifically, Taubes is well versed in cholesterol and should have been able to respond intelligently instead of with the litany of excuses.
The diet section of WWGF is short, but Taubes has now graduated to "diet book" author and as such is more than just challenging the status quo, he's advocating for a pretty extreme WOE. Anyone who doesn't think practically zer0 carbs is extreme is kidding themselves. Statistically zero humans in the context of our entire species have ever eaten that way, historically or otherwise.
So, if he is going to publish his personal test results, he should do it in a legitimate fashion. This man has connections and could easily get hooked up with a personal physician sympathetic to low carbing and cholesterol levels that may be slightly out of sync by other standards but perfectly normal and healthy. It is Taubes who seems incapable of having an adult conversation with a doctor in the context of a medical examination. Why else would someone call up an out of state doctor friend to order up the test? Really, why not anyone else? So that if he didn't like the numbers nobody, including a doctor he might entrust with his health and consult for advice, would know?
Quest is a mainstream testing lab in the States. It's not a big deal to go for a checkup and have a doctor write the order for tests. It's really not expensive either, even if you have to pay for a visit out of pocket.
But as to that doctor friend, that he's a member of the ABBM only detracts from that organization. Read his website. His diet is zer0 carbs and injections so that you eat as little as humanly possible to lose weight as fast as possible. And if those injections aren't enough, he's got a bunch of other drugs to try. Sound familiar ... sans the injections and other drugs?? This is who Taubes went to to circumvent going for a routine checkup. It's repetitive I know, but if anyone else did this everyone would be jumping on it like gangbusters and you know it.
I hope GT addresses his borderline/developing acidosis for his own sake.
I thought myristic acid just as potent, if not more so?
http://www.ncbi.nlm.nih.gov/pubmed/8148355
Conspiracy theories can be endlessly concocted by doubting anything one desires. It makes more sense to accept a claim as true or mistaken rather than part of a deception, especially when credibility is at stake. Deception may be isolated when more facts about the circumstances are known. Here is an example of a viable conspiracy theory:
http://www.youtube.com/watch?v=gVKvzHWuJRU
Also, is there some evidence that "borderline/developing acidosis" causes death or disability? Or is this one of those "strong association" statements that lead to irrational conclusions like "our economic problems are strongly associated with having too many Jews"?
'Bad' Cholesterol Not as Bad as People Think, Study Shows
"Riechman and colleagues examined 52 adults from ages to 60 to 69 who were in generally good health but not physically active, and none of them were participating in a training program. The study showed that after fairly vigorous workouts, participants who had gained the most muscle mass also had the highest levels of LDL (bad) cholesterol, "a very unexpected result and one that surprised us."
"LDL serves a very useful purpose. It acts as a warning sign that something is wrong and it signals the body to these warning signs. It does its job the way it is supposed to.
"People often say, 'I want to get rid of all my bad (LDL) cholesterol,' but the fact is, if you did so, you would die," the Texas A&M professor adds. "Everyone needs a certain amount of both LDL and HDL in their bodies. We need to change this idea of LDL always being the evil thing -- we all need it, and we need it to do its job."
"The bottom line is that LDL -- the bad cholesterol -- serves as a reminder that something is wrong and we need to find out what it is," Riechman says.
"It gives us warning signs. Is smoking the problem, is it diet, is it lack of exercise that a person's cholesterol is too high? It plays a very useful role, does the job it was intended to do, and we need to back off by always calling it 'bad' cholesterol because it is not totally bad."
Then Dr. Gofman asked people about their health and diet. He learned that having high LDL or high triglycerides correlated with an increased risk of heart disease, high HDL correlated with a low risk of heart disease, and that the two profiles responded entirely differently to foods in the diet. (He also learned that cholesterol could be packaged either tightly clustered or loosely assembled within LDL; measuring it did little to reflect this risk.) Saturated fat raised LDL, while carbohydrates raised triglycerides, ultimately lowering HDL. (Dr. Gofman even recognized that LDL was made up of subtypes, although the meaning of the diversity was unclear at first.) It was groundbreaking work, but too advanced for the movement it ultimately spawned. With so few analytical ultracentrifuges available, researchers began using cheaper methods of counting lipoproteins, methods now offered during routine physicals. One form of cholesterol became "good," the other "bad."
Dr. Krauss was working part-time in Dr. Gofman's old lab and flipping through some data cards when he noticed a correlation that would change everything. As he combed through a recently completed study of 80 men and 54 women in Modesto, California, Dr. Krauss noticed that the people with low HDL tended to have high LDL. But not just any LDL was elevated; only the smaller forms observable to Dr. Gofman's analytical ultracentrifuge.
"I started studying these readouts, and what popped out were some amazingly strong inverse correlations," he says, still amazed at his good fortune. "It was just sitting there in the data." Dr. Krauss had found that small, dense LDL particles were the evil twin of good cholesterol. HDL and small LDL tended to move at the same time, he discovered, but in opposite directions. If your smaller forms of LDL were high, your HDL was low; if your smaller forms of LDL were low, your HDL was high. Whether one was the cause and the other was the effect was unclear, but given the newly discovered importance of HDL, the importance of smaller forms of LDL was now real.
Dr. Krauss discovered that while a diet high in saturated fat from dairy products would indeed make your LDL levels rise, "saturated fat intake results in an increase of larger LDL rather than smaller LDL particles," as he wrote in an American Journal of Clinical Nutrition review he co-authored in 2006. A diet heavy in full-fat cheese and butter — but not overloaded in calories — triggered the relatively harmless health profile described as pattern A. (Having demonstrated the benign consequences for cholesterol from consuming dairy fat, he is currently conducting studies to find out if the same holds true for diets high in saturated fat from beef.)
Not only is dairy fat unlikely to increase heart-disease risk, Dr. Krauss and others have learned, but reducing saturated fat in a way that increases carbohydrates in a diet can shift a person's LDL profile from safe to dangerous. That's pretty much what happens whenever some well-meaning person with "high LDL" starts eating "low-fat" frozen dinners filled out with corn-derived additives, all the while engaging in the customary ravaging of a basket filled with dinner rolls.
http://www.meandmydiabetes.com/2012/04/17/ron-krauss-saturated-fat-red-meat-it-depends/
When I'd mentioned previously that IIRC he'd said fairly early on, "We're all taking a big risk", that was something that was never repeated... not in the slightest.
So beef + SFA results in Pattern B, while dairy does not. Surprising. Krauss *guesses* (not stating with the certainty that LC advocates use when discussing unproven topics) that it might be from the heme iron in red meat.
So why didn't Dayspring give this illuminating evidence even the tiniest mention in his long interview with Jimmy? Maybe a clue is that it's not consistent with carbophobic marketing.
I'm taking a quick look around all the Paleo/LC advocate sites, so far I'm seeing all of them mentioning Krauss' work that supports their own view, but somehow they didn't mention this newer evidence from Krauss. Imagine that.
Any Kresser fans here? Can you show me where Kresser mentions this?
https://www.google.com/search?q=site%3Achriskresser.com+krauss
Here's a strategy to do it: do fasting to lower LDL, meanwhile try to keep HDL as high as possible with niacin and perhaps alcohol.
Then again, steroid or narcotics metabolites can be found in blood long after a high LDL count has gone away - the athletes maybe would have to come back *months* later.
I had to laugh, too, that Taubes posting an image of test results on his website is somehow considered sufficient. Maybe we can use that style in the court system: Your Honor, the defendant says he is innocent so we have to take his word for it.
No one would ever be less than honest when prestige and lots of money are at stake, no no no.
__________
Not even the less-emphatic form of the standard legal boiler plate "check with your doctor" stuff?
But I did find an **older** page (2010): "Steric is likely cardio protective, Lauric neutral, palmitic (due to actions on LDL production and Leptin/Insulin sensitivity) may be a problem."
http://robbwolf.com/2008/04/11/weston-price-vs-paleo/
And there's Kresser quoting the older Krauss data that SFA is safe. I haven't seen Kresser discussing anywhere the current study about beef. Surprise again.
Back to the Krauss interview: he says that they used a very high level of SFA, 15% of calories, and found small raising of LDL. Can anyone calculate what percentage of SFA is found in a Wolf/Lalonde/Jimmy type of diet?
(~10:25 in the Krauss audio interview - also note that the transcript is not entirely accurate)
"You have to fast for about 12 hours before the test because triglyceride levels can shoot up 20%-30% after a meal, which would throw off the equation"
http://www.health.harvard.edu/newsweek/Which_cholesterol_test_should_you_get.htm
I would guess that there is some reason for telling patients to fast 12 hours before the test, but I haven't looked deeper into it.
AJCN. First published ahead of print July 3, 2012 as doi: 10.3945/ajcn.112.037770.
Dietary intake of saturated fat by food source and incident
cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis
Results:
After adjustment for demographics, lifestyle, and dietary confounders, a higher intake of dairy SF was associated with lower CVD risk [HR (95% CI) for +5 g/d and +5% of energy from dairy SF: 0.79 (0.68, 0.92) and 0.62 (0.47, 0.82), respectively]. In contrast, a higher intake of meat SF was associated with greater CVD risk [HR (95% CI) for +5 g/d and a +5% of energy from meat SF: 1.26 (1.02, 1.54) and 1.48 (0.98, 2.23), respectively]. The substitution of 2% of energy from meat SF with energy from dairy SF was associated with a 25% lower CVD risk [HR (95% CI): 0.75 (0.63, 0.91)]. No associations were observed between plant or butter SF and CVD risk, but ranges of intakes were narrow.
Conclusion: Associations of SF with health may depend on foodspecific
fatty acids or other nutrient constituents in foods that contain SF, in addition to SF.
DISCUSSION
In this large multiethnic cohort, a higher intake of dairy SF was inversely associated with lower CVD risk. In contrast, a higher intake of meat SF was associated with higher CVD risk. Total SF was associated with slightly lower risk of incident CVD; this effect was driven by dairy SF, which was the greatest contributor to total SF consumption in this population. We observed no significant associations of plant or butter SF with CVD risk, but ranges of intake of SF from these sources were narrow.
In conclusion, we showed that associations between SF and incident CVD depend on the food source; the consumption of dairy SF is inversely associated with risk, and the consumption of meat SF is positively associated with risk. Our findings raise the possibility that associations of foods that contain SF with health may depend on specific fatty acids present in these foods or the complex admixture of other food constituents, in addition to SF.
Prediction: any future assaults on Krauss' beef study will include, "but he didn't use grassfed blah blah blah".
P.S. That is the MESA study, the subanalysis from which most formally established particle number as the real factor behind the *association* of lesser atherogenicity with large fluffy particles. Supposedly.
Btw, LC advocate Dayspring also says, IIRC, that LDLs which are too large are also a problem in being taken out of circulation by LDL receptors. Plus, let's not forget that when a large particle gets into the artery wall, it does bring more cholesterol than a smaller particle.
I would highly recommend Dayspring presentations like the following for their info-dense content on terminology and purported mechanisms. I personally wouldn't trust his conclusions:
http://www.lecturepad.org/index.php?option=com_content&view=article&id=1071&catid=154&Itemid=382
It's about an hour, even the Flash player is great. There are also other presentations there.
Meanwhile, anybody's LDL will decline with reduced calories - even on the Twinkie diet. Well, I guess there can always be exceptions - such as sometimes when diabetics see BG rise when fasting.
Speaking of diabetes, just as testing BG levels after eating can give an earlier indication of a problem (earlier than a fasting test does), so we might see postprandial TAG testing come to replace fasting TAG testing. That's the kind of testing used in the Homburg Cream and Sugar study, e.g.
I have been watching movies about World War II lately. In one scene a soldier gives a girl a chocolate bar. This reminded me that the recent increase in obesity is even affecting the military. THE MILITARY! So the idea that the increase in obesity is caused by laziness or a lack of discipline or exercise is absurd. There are factors in play that have not been discovered.
This hyper-focus on saturated fat just seems crazy. Any little "blip" in differences is looked at like some kind of revelation. The rise in obesity can be traced to an increase in consumption of ALL macro-nutrients. The problem is that we don't know WHY there is an increase in consumption of all macro-nutrients.
---An increase in lottery winners from West Virginia is not proof of that the lottery is fixed...or that we have figured out an advantage!---
That reminds me, I never did see a listing of various lipoprotein diameters compared to the range of distances between endothelial cells. As you know, the idea is that large LDLs are too large to get through.
LC advocate Dayspring uses the usual imagery, I think: the lipoprotein "smashes" into the artery wall. That'd tend to mean that there would be more atheroma in certain areas: where an artery bifurcates, that 'Y' would get hit with force, and also the curves would tend to get hit - just like in any stream or river. IIRC, in many atheromas that require revascularization, that is true. Many, but not all.
But look at Dayspring's own example:
http://www.lecturepad.org/index.php?option=com_content&view=article&id=1071&catid=154&Itemid=382
Click on slide #2 on the column at left of thumbnails. That is apparently an actual very-occluded artery (from Circulation, 2007) and it is as straight as can be. Imagine any LDL being swept along through the artery and it has to take a sharp turn to "smash" perpendicularly into the artery. That makes no sense, of course - and is a big weakness in the "large LDL can't penetrate" theory. Imagine vertically holding a cardboard tube from paper towels and pouring a handful of rice through - there is no smashing against the sides.
As far as the intercellular gaps, I'd think that inflammation maybe comes into play: as the artery dilates from histamine and other vasodilators, proteases can loosen the "tight junction" proteins that bind them together... so inter-endothelial spaces widen. I never see that mentioned but it's got to be somewhere. If you used a marker to draw rectangles on a balloon, then inflate the balloon more (like vasodilation), then the spaces between rectangles get farther.
That still doesn't explain how LPs can make sharp turns and smash into straight artery walls. My guess is that they don't have to, that they alternatively can adhere to the artery first and then some process takes them inside - similar to leukocyte extravasation, except LPs can't locomote on their own. There might be something similar to Cellular Adhesion Molecules (CAMs) on endothelial cells, but used for LPs instead of for leukocytes.
Presumably, LPs have fairly stiff structure and can't squeeze through gaps. That'd be opposite to the way that monocytes and neutrophils can almost pour themselves through small gaps - like in Terminator 2. Or how red blood cells can usually be squeezed through tiny capillaries.
My guess is that no one really knows how any LP gets under the endothelium, but that's just a guess.
I decided to do something about it. I considered medical school, with the intention of helping to reform the industry from the inside out. But while allopathic medicine excels at emergency and trauma care, it isn’t very good at fostering health. (In fact the subject of health rarely comes up at all in conventional medical textbooks, which are entirely focused on disease.)
I chose instead to study Chinese medicine, which has been successfully used for over 2,000 years to promote health and longevity in addition to treating disease. Whereas Western medicine uses powerful chemicals or invasive surgery to achieve its goals, acupuncture works by stimulating the body’s highly sophisticated self-healing mechanisms. This made so much more sense to me – especially as I learned more about the dangers of pharmaceutical drugs and the impact of medical errors.
I have complemented my study of acupuncture and herbs with a thorough education in functional medicine. Functional medicine is a personalized approach to health care that recognizes the biological uniqueness of each patient. In contrast to conventional care, which is almost entirely focused on suppressing symptoms, functional medicine eliminates symptoms by addressing the underlying cause of a problem. It is an evidence-based field of health care that views the body as an interconnected whole, and recognizes the importance of these connections in health and disease. In functional medicine, the patient is empowered, educated and encouraged to play an active role in the healing process.
I graduated from the Acupuncture and Integrative Medicine College in Berkeley in April 2010. I passed the California Acupuncture Licensing Exam in August of 2010, and I have a private practice in Berkeley, CA. I also consult with patients nationally and internationally.
He's also selling this for $147.00
http://highcholesterolplan.chriskresser.com/
It turns out that not only is the amount of LDL important, but so is its size. Remember, LDL is the cholesterol that floats around in the blood and can get into the arteries. The barrier to this is in large part the "endothelium", the cells that line the arteries. The endothelial cells are very close together and form a carpet. This carpet is made up of individual cells, and there are small areas in between them that allow small particles to pass back and forth through the artery wall. The artery needs to have access to the oxygen and other nutrients in the blood, so these small "holes" make sense. By small, we mean really small . . . around 260 millionths of an inch! (A millionth of an inch is called an "Angstrom"). It makes some sense that the smaller the LDL, the more likely it is to be able to cross the wall. It turns out that most of our LDL is right around that 260 Angstrom size.
How much difference does a few millionths of an inch make? A 5% smaller diameter LDL particle leads to a 50% increase in the rate of uptake by the arterial wall! LDL particles less than 258 Angstroms can get through the holes between cells quite easily and are therefore can be quite "atherogenic" (that is, cause blockages in the arteries). Those larger than 263 Angstroms are much less likely to cause blocked arteries. Now, we all have LDL particles that range from 200-300 Angstroms. It is the "peak" LDL size that has much to do with determining our atherosclerotic risk. If we have predominantly large LDL, we're called "Pattern A", if we have lots of the nasty small LDL we're called "Pattern B". Those with LDL between 258 and 263 are intermediate, or "Pattern I".
__________
his stances seem reasonable, non-extremist, and he hasn't joined the anti-vaxers (yet, that I know of)
Can't discard everything someone writes just based on that, BUuuuut ...
> successfully used for over 2,000 years
appeal to antiquity ... Ayurveda/Aryuveda beats that hands down BTW
(I started taking the "about" apart but really it's pretty standard alt-med stuff - Steve Novella, ORAC, and others do a much better job of it than I ever can)
doing reasonable to great work in a lot of fields but some areas held separate from questioning.
Heart disease is not the only way to die, nor is it necessarily the worst of possible deaths, and the focus on the heart as the be-all and end-all on health is a throwback to primitive magical thinking.
If a high-sugar diet, overweight, 40 cigarettes a day and zero exercise finds you with an LDL that's "HH", does this make you as healthy as an active VLC dieter who has the same reading?
_____
they're proposing physical smashing as the main mechanism lipoproteins get into the artery wall?
Is that any kind of current consensus?
for physical smashing, smaller denser particles would maintain more speed through a viscous fluid - if they somehow got a vector that crashes them into the wall.
What about just being squished against the wall by irregularly shaped cells? In this case I can imagine larger particles being less able to "get out of the squeeze"
"So why does having an LDL-P of 2,000 nmol/L (95th percentile) increase the risk of atherosclerosis relative to, say, 1,000 nmol/L (20th percentile)? In the end, it’s a probabilistic game. The more particles – NOT cholesterol molecules within the particles and not the size of the LDL particles – you have, the more likely the chance a LDL-P is going to ding an endothelial cell, squeeze into the sub-endothelial space and begin the process of atherosclerosis."
What about the other apoB containing lipoproteins?
Beyond the LDL particle, other apoB-containing lipoproteins also play a role in the development of atherosclerosis, especially in an increasingly insulin resistant population like ours. In fact, there is some evidence that particle-for-particle Lp(a) is actually even more atherogenic than LDL (though we have far fewer of them). You’ll recall that Lp(a) is simply an LDL particle to which another protein called apoprotein(a) is attached, which is both a prothrombotic protein as well as a carrier of oxidized lipids – neither of which you want in a plaque. The apo(a) also retards clearance of Lp(a) thus enhancing LDL-P levels. It may foster greater penetration of the endothelium and/or greater retention within the sub-endothelial space and/or elicit an even greater immune response.
In summary
The progression from a completely normal artery to an atherosclerotic one which may or may not be “clogged” follows a very clear path: an apoB containing particle gets past the endothelial layer into the sub-endothelial space, the particle and its cholesterol content is retained and oxidized, immune cells arrive, an initially-beneficial inflammatory response occurs that ultimately becomes maladaptive leading to complex plaque.
While inflammation plays a key role in this process, it’s the penetration of the apoB particle, with its sterol passengers, of the endothelium and retention within the sub-endothelial space that drive the process.
The most numerous apoB containing lipoprotein in this process is certainly the LDL particle, however Lp(a) (if present) and other apoB containing lipoproteins may play a role.
If you want to stop atherosclerosis, you must lower the LDL particle number."
This is almost directly opposing what Krauss says - that's saize matters not the number
Would you agree with me then? A reason for GT not to take the test would be because he knew he wasn't fasted and therefor his result would be skewed?
The "blip" in odds ratios seen with fat, and indeed most dietary variation for most diseases, is tiny indeed compared for the odds ratios seen when looking at parasites and other infectious agents and their correlation with disease, both protective and otherwise.
"Hygiene hypothesis" epidemiology is generating the kind of statistics that dietary epidemiologists can only dream about.
The inflammation connection.
It''s early days yet, but I'd put most of my bets on the microbiota, and guess that much of the effect of diet on disease is prebiotic (so to speak) rather than metabolic.
I believe that dairy fat, especially butter, is actually more saturated than fat in meat; for example, tallow, perhaps the most saturated animal fat, is 50% SFA, while butter is 63%.
Much meat fat consumed is pork fat, which is not highly saturated.
Never forget: http://jn.nutrition.org/content/134/4/904.full
Then again, fasting would throw off TAG more than LDL. TAG is to blood glucose testing as LDL is to HgbA1c. It takes the longer view. So while his TAG number would possibly have been off, his LDL number wouldn't be off so much AFAIK.
But even then TAG after a fatty non-carb meal drops back to baseline within a few hours, so he would have that arguing against his claim.
no, I never took it that they meant that the LP traverses endothelial cells, penetrating the membrane then coming out the other side (but biochemicals do that, IIRC nitroglycerin does). I'd guess they're trying to account for the atherogenic effect of hypertension, in that the LPs are forcefully getting through the spaces between endothelial cells.
wrt to Lp(a), IIRC that is low in Familial Hypercholesterolemia, is it not? Lp(a) is yet another marker which sounded great then didn't pan out. I even remember a paper saying that Lp(a) is so oxidized because it might be carrying oxidized molecules out of the plaque - it's possibly the fire truck in the often used analogy about fire trucks not causing the fires. At least Attia uses words "may" instead of pretending that uncertain things are certain.
I think that's postulated, not known. It could explain why taking lots of antioxidants does not prevent heart disease (antioxidants are in the serum where they would protect circulating LDL, but not in the subendothelial space). But AFAIK that's a guess, not a fact.
next quote:
"leading to complex plaque"
huh? My impression is that complex plaque involves previous minor rupture and some remaining thrombosis. Not every rupture and atherothrombosis ends in death, some are minor. So not every plaque is complex (or complicated). Let's look it up:
complicated plaque:
Vascular disease An advanced or fully developed lesion of atherosclerosis, defined as one or more of the following: rupture or fracture of the fibrous cap of the fibrous plaque, hemorrhage into the plaque, mural thrombosis, prominent fibrosis
http://medical-dictionary.thefreedictionary.com/complicated+plaque
or
"large complex plaques (those with ulcerations or mobile components) "
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854144/
(from Circulation 2010)
I take back my compliment about Attia :) That is, unless I'm wrong and he's right; but those two cites don't seem to agree with Attia that a "clear path" to a necessarily complex plaque as he describes is correct. Many times, the 1st rupture is the only one.
quoting Charles one last time: "This is almost directly opposing what Krauss says - that's saize matters not the number"
well no, I'd say that Krauss and Attia and Dayspring all agree that particle number is the danger. Dayspring explicitly says particle size doesn't matter at all, they all get beneath the endothelium. Krauss showed data that SFA doesn't increase number of small dense LDL, then later showed that SFA from/with beef does indeed increase number - 25% higher IIRC than from dairy.
And what about Krauss saying that diets above a certain carb % shift the pattern to small, dense from large buoyant?
If the optimal is LDL-P below a certain number with the small LDL-P being as close to zero as possible what diet would get you there?
Dayspring did suggest to Jimmy that if his dietary n=1 experiment doesn't reduce his LDL-P then he (Jimmy)should consider using a statin.
But - according to all of the paleo experts and others statins are so bad they should never be used at all?
Confusion still reigns.
http://www.foxnews.com/science/2012/10/15/chinese-scientist-says-prehistoric-humans-ate-pandas/
Regarding possible causes of obesity and heart disease: I think the hygiene hypothesis has some merit. But I would not rule out a vector borne cause that has yet to be discovered. If there is a causative agent (or missing agent), then it seems likely that it affects the hypothalamus. Other parts of the brain might also be targets.
Some questions are:
Why has there been an increase in obesity?
Why has there been an increase in autism?
Why has there been an increase in diabetes?
Why don't all obese people get type 2 diabetes or vice versa?
The whole "fat people are just out of control" idea is completely bogus, in my opinion. Something seems to be affecting the brain/appetite which causes an increased desire for certain foods. It may be something that is either introduced into the body or destroyed in the body through the consumption of certain foods.
Whatever it is, it isn't new but it certain did become more effective. It may be prionoid and would appear as a protein therefore making it extremely difficult to detect. The etiology of prions are also poorly understood.
Re LDL causing inflamation, why? And when do macrophages enter the picture?
All in all, after so many years of study, it is remarkable how little is known about the etiology of atherosclerosis.
Particles smaller than 70nm can pass through the endothelium. However, particles are only atherogenic if, after they pass through the endothelium, they are retained and taken up my macrophages. HDL partcles pass in an out and cause no problem. LDL particles, on the other hand, are often retained. There are two competing theories about what make LDL particles atherogenic. The first is the response-to-retention hypothesis which is the dominant theory of lipid researchers and the one held by Dayspring (and summarized by Attia). One version of this theory holds that Apolipoprotein B binds avidly to arterial proteoglycans and thus is retained. The alternative theory is the oxidative modification hypothesis. It holds that LDL in its natural state is not atherogenic, but that once it is modified by oxidation, it is susceptible to macrophage uptake. Daniel Steinberg first proposed this theory, and it is advocated by Chris Masterjohn.
"In the 1999-2000 period obesity prevalence in men peaked in the 60-74 age range. Why? With progress in medicine, it is likely that more obese people in that age range survived (however miserably) in the 1999-2000 period. Obesity prevalence overall tends to be highest between ages 40-74 in women, which is a wider range than in men. Keep in mind that women tend to also live longer than men.
Because age seems to be a factor in obesity prevalence among urbanites, it would be reasonable to look for a factor that significantly increased survival rates as one of the main reasons for the steep increase in the prevalence of obesity in the USA in the 1980s. If significantly more people were surviving beyond age 40 in the 1980s and beyond, this would help explain the steep increase in obesity prevalence. People don’t die immediately after they become obese; obesity is a “disease” that first and foremost impairs quality of life for many years before it kills.
Now look at the graph below, from an article by Armstrong and colleagues (7). It shows a significant decrease in mortality from infectious diseases in the USA since 1900, reaching a minimum point between 1950 and 1960 (possibly 1955), and remaining low afterwards. (The spike in 1918 is due to the influenza pandemic.) At the same time, mortality from non-infectious diseases remains relatively stable over the same period, leading to a similar decrease in overall mortality."
"When proper treatment options are not available, infectious diseases kill disproportionately at ages 15 and under (8). Someone who was 15 years old in the USA in 1955 would have been 40 years old in 1980, if he or she survived. Had this person been obese, this would have been just in time to contribute to the steep increase in obesity trends in the USA. This increase would be cumulative; if this person were to live to the age of 70, he or she would be contributing to the obesity statistics up to 2010.
Americans are clearly eating more, particularly highly palatable industrialized foods whose calorie-to-nutrient ratio is high. Americans are also less active. But one of the fundamental reasons for the sharp increase in obesity rates in the USA since the 1980s is that Americans have been surviving beyond age 40 in significantly greater numbers.
This is due to the success of modern medicine and public health is dealing with infectious diseases."
From the Centers for Disease Control:
"In the most recent period from 1969 to 2010, significant progress in the prevention, diagnosis, and treatment of cardiovascular diseases likely contributed to the 41 percent decline in age-adjusted mortality despite cancer continuing to increase from 1969 to 1990 and chronic lower respiratory diseases continuing to increase from 1969 to 1998."
Reference: http://www.cdc.gov/nchs/data/databriefs/db88.htm
http://www.cell.com/molecular-cell/abstract/S1097-2765(12)00779-4
"We propose that the membrane proximal domain rigidification in the context of a liganded cytokine receptor dimer is a key mechanism for the transactivation of Janus kinases (Jaks) bound at the intracellular receptor region."
Sometimes scientists can sound like such a pain in the Janus kinase...
I see what you mean about Krauss and size. While in that recent interview http://www.meandmydiabetes.com/2012/04/17/ron-krauss-saturated-fat-red-meat-it-depends/
at 06:38 he clearly says "but it's the particle number that matters", a few seconds later he's talking about size again: "And looking even deeper, when the total number of LDL particles is higher than normal, I and many of my colleagues would argue that the biggest concern is warranted when the number of smaller particles is high, not the larger ones."
So Dayspring says size doesn't matter, only number. The MESA analysis says size gets explained away by number. Nobody apparently believes anymore in Pattern A versus B, which is only a ratio and doesn't take overall number into account.
Btw, Krauss started the whole research into size.
Some quotes from his earlier interview, March 2010 same site:
http://www.meandmydiabetes.com/2010/03/26/ldl-cholesterol-ron-krauss-md/
"The fat that causes LDL to go up is saturated fat. Animal fat."
As far as FH (which relates to the idea that large LDL in FH shows that large LDL isn't protective): "These kinds of people have all kinds of LDL. Large and small. Whether or not it’s the small particle LDL that causes it, we don’t know. They have too much of everything."
Right before that, he discusses people with genetically very low LDL having no health problems because of it. I remember a Mercola article arguing that getting LDL too low is dangerous.
http://www.science20.com/news_articles/obesity_virus_can_ad36_cold_virus_make_kids_fat
I might point out that the loss of some infections seems to promote the harmful effects of others. For example, ad36 may not be obesigenic in children who have been exposed to pinworm (just a mad hypothetical example off the top of my head, but possibly true). And it is also unlikely to be obesigenic in many kids who aren't being fed sweetened milk, pink slime, corn this and corn that, all cooked in corn oil, fructose and gluten.
http://www.huffingtonpost.com/andrew-weil-md/carbohydrates-weight-loss_b_1937312.html?utm_hp_ref=diet-and-nutrition
and
http://www.drweil.com/drw/u/ART03415/Using-The-Carbohydrate-Density-Index.html
Kinda looks like it to me.
http://news.yahoo.com/blogs/sideshow/96-old-claims-world-oldest-father-video-202603744.html
There is another kind of cherry picking that doesn't get much attention. The kind where we pretend the high frequency of such outliers don't exist or matter.
To me it is cranking up the insanity like Chef Emeril cranks up the flavor BAMM!insanity to the nth power
Want to munch on some delicious recipes TONIGHT?
Get your awesome Paleohacks Cookbook.
Post a Comment
Comment Moderation is ON ... I will NOT be routinely reviewing or publishing comments at this time..