TPNS 43-45: Anything But LDL

Primitive Nutrition 43:
Anything but LDL, Part I

Here's a quick disclaimer to start this video.  My Anything but LDL presentation might get a bit tedious for some of you.  If you want to skip it I'll understand.  The point of this section is that you shouldn't be impressed with all the biomarkers low carbers name to make it seem like their diet strategy is healthy.  Levels of total cholesterol and LDL bad cholesterol are probably the best risk factors for heart disease out there.  Doctors know this, and they also know how to interpret all the other biomarkers to treat their patients properly.  Stay focused on lowering your total and LDL cholesterol numbers, listen to your doctor, and eat a prudent diet high in whole plant foods and you won't ever need to contemplate the alphabet soup of other biomarkers.

And now on to the content.

As you might be able to tell, I've been observing the low carb world with interest recently.  I've noticed that some low carbers say cholesterol is good for you while others claim their diet is great because it can lower cholesterol.  They can't seem to get there story straight on this molecule.

Those who want you to just ignore the whole issue of cholesterol almost always start their pitch by informing you that your body needs cholesterol.  Here Mark Sisson, in one of his articles he immodestly calls definitive, follows this formula.  He wants you to think of cholesterol in simple caveman terms: cholesterol good!

As if the scientists who have advised us to keep our cholesterol low have no idea what it actually does.

It also seems that some believe certain biomarkers, or measurable substances in the blood, are better for assessing heart health than cholesterol.  Let's take a look at a few of these and see if they're really any better than good old LDL bad cholesterol.  But first, it must be understood that all that really matters is the clinical endpoint.  In heart disease, that means something like a heart attack or heart failure.  Doctors use biomarkers because they are considered the best indicators of risk in situations where they can't observe a problem directly.  Biomarkers are just surrogates and they shouldn't be thought of as substitutes for the real endpoints.

For example, vegetables were here shown to be able to turn back heart disease in mice despite biomarkers that wouldn't have suggested this was happening.  Biomarkers aren't perfect.

Doctors sometimes use formulas based on risk factors to calculate heart health.  They aren't necessarily any more reliable for uncovering heart disease.

Let's look at some of these other biomarkers.  Uffe Ravnskov is a believer in coagulants in the blood like fibrinogen.  I guess the logic is that atherosclerotic plaque is ok as long as when pieces of it come loose they don't form a clot.  He might be heartened to know that low fat diets and hempseed can reduce coagulant activity.

Fruits and vegetables are good for that, too.  So plants are good for this issue.  Did you see that coming?  Get used to it.

Ravnskov's hypothesis about fibrinogen may not be worth much.  Experiments on genetically altered mice don't really validate the importance of fibrinogen.

Low carbers say triglycerides are a problem caused by carbs. 

However, triglycerides don't seem to predict clinical endpoints better than cholesterol.

It seems triglycerides are adversely affected by junk food carbs. 

But healthy complex carbs don't seem to cause much of an increase.

Any elevation in triglycerides seen after eating healthy carbs on a low-fat diet doesn't represent the same metabolic conditions as in high fat diets.

If keeping your triglycerides in check is your aim, then a healthy, fiber-rich vegan diet is a good option.  Plants are great for this, too.

What about the idea that it's more important that your HDL, or good cholesterol, be kept high?  This is a big one for the low carbers.

This is an idea lacking in support right now.

You may have heard about the big clinical trial that was stopped by the NIH looking into niacin and statin interventions to raise HDL.  HDL went up and triglycerides went down, but it wasn't helping these patients. I've heard this study used to argue that high-HDL is not protective.  However, often overlooked is the fact that all participants  in this trial were on aggressive drug treatments to lower their LDL.  The study may just mean that if LDL is low, you don't need high HDL.

LDL seems to be a much more useful biomarker than HDL for cardiovascular disease.

It's been known for a while that healthy low-fat diets reduce HDL by changes in the clearance rate of cholesterol from the blood, so again, we have a biomarker that means different things in different contexts.

It is understood now that the HDL idea needs some refining.

This important study also showed that a healthy high-fiber diet changes the nature of the HDL from pro- to anti-inflammatory, meaning the HDL could offer better protection.  Plants win again.

Low carbers are very invested in the idea that they are safe with higher LDL scores because their LDL particles are larger, which is somehow better.

They should know that all LDLs are atherogenic.  You see here that the large ones do indeed correspond with people eating high saturated fat diets.  Those particles hold more cholesterol. 

LDL particle size measurements may only be useful in patients with borderline-high total LDL.

It's been shown that when calories are kept constant, switching from high-fat to lower-fat diets lowers the levels of the small, dense LDLs the low carbers say they are trying to avoid.

If you want to reduce your small, dense LDLs, eat healthy plant foods, which reduce them along with total cholesterol.

You may have heard there is a so-called ultra-bad LDL that occurs when LDL is glycated, or attached to a sugar molecule. 

It is especially associated with diabetes.  A molecule called methylglyoxal causes the glycation. Forgive me for a little speculation here.  I want to play connect the dots.

For what it's worth, in this study, aminoacetone increased methylglyoxal more than sugars.

This study in rats showed that aminoacetone caused iron in the blood to damage mitochondria.  Iron overload and aminoacetone may play an important role in diabetes.  You know a bit about iron by now from my Protein Choices video.

For now, notice that the most important sources of threonine, which is needed to produce aminoacetone, are meats, unless for some reason you are eating a ton of watercresss or seaweed.

I hope you're not getting sick of biomarkers already.  There's much more in Part II!

Primitive Nutrition 44:
Anything but LDL, Part II

Low carbers also talk a lot about the issue of oxidized LDL.

Measurements of oxidized LDL may not be a reliable indicator of risk.  What is being detected may just be oxidized LDL fluxing out of arterial plaque, which is a good thing.  This is why it sometimes goes up on healthy low-fat diets.

Increases in oxidized lipids occur when damaged arteries are healing.

Oxidized LDL may be beneficial in certain contexts.  Some think it doesn't really lend itself to targeted therapy.

This may be why clinical trials of isolated antioxidants have been disappointing.  Oxidized lipids don't seem to be very good biomarkers.

Internet cholesterol confusionist Chris Masterjohn puts a lot of faith in the oxidative modification hypothesis.  He is concerned about what this stuff does to damage the layer of endothelial cells that line our arteries.  That would interfere with the production of nitric oxide, something your arteries need to stay healthy.

Caldwell Esselstyn of the Cleveland Clinic is concerned about this as well, which is why he recommends a plant-based diet, unlike Masterjohn.  He explains his reasoning in this book.

Daniel Steinberg has been one of the leading researchers in the study of oxidative stress on LDL.  He wants better drugs to control this.  Surely Masterjohn would not disagree on this subject with an authority of the stature of Steinberg, who shares his interest in oxidative modification.

I wouldn't disagree with him, either.  I agree with other comments he has made as well: High LDL is sufficient to cause heart disease.  Adopting dietary strategies to lower LDL is advisable.  LDL levels should be as low as possible.  I couldn’t agree more.  But Masterjohn would disagree with these statements. 

They both know the effect of diet on the integrity of the LDL particle.  However, only one has a personal investment in dangerous low-carb diets.  And only one is an undisputed leader in lipid research.  Guess who is who.

Masterjohn knows compounds found in plants fight this oxidation.  He mentions polyphenols.

And he is right about that.  They are found in plants and known to improve the health of the endothelium.

Fruits and vegetables are known to generally fight inflammation and oxidation.

And they help your lipoproteins this way as well.

Meanwhile, dietary cholesterol has been shown to promote LDL oxidation. 

The pharmaceutical industry is only too happy to find drugs to treat oxidation and inflammation.  But realize we are no longer talking about *preventing plaque buildup with this approach, and we are no longer talking about food.

The endothelial cells use nitric oxide to dilate vessels to allow greater blood flow.  This was shown to be adversely affected by low carb diets in this study...

and in this study.

Maybe it's because the saturated fat in those diets impairs endothelial function.

On the other hand, a vegan diet decreased oxidized LDL and total LDL in this study.  So why doesn't Masterjohn advocate a diet with lots of fruits and vegetables and minimal saturated fat and cholesterol if he thinks this is an important issue?

Loren Cordain.  meandmydiabetes.com

Let's talk about inflammation.  Another primitive idea is that plaque doesn't matter.  What matters is the inflammation.  Here is Loren Cordain saying that arterial plaque is fine as long as it doesn't break off and give you a heart attack.  I'm not sure why it wouldn't be better to not have that plaque there in the first place.  Cordain is making the argument that inflammation is the real problem.  If you have low inflammation, you have nothing to worry about.

This is an odd stance for him of all people because the relationship between inflammation and heart disease doesn't seem to exist in hunter gatherers.  This is an inconvenient study for him, I imagine.  These hunter gatherers had high levels of inflammation, but hardly any heart disease.  By the way, they did have parasites.

Of course, pharmaceutical companies welcome the prospect of treating inflammation in heart disease.  New drugs await discovery.  And they will probably help.

It should be noted, though, that it has been demonstrated that everyone's favorite biomarker of inflammation, C-reactive protein, or CRP, has been shown to arise from reverse causation in the context of heart disease.

Inflammatory biomarkers don't seem to be responsible for increasing atherosclerosis.

And they don't seem to cause vascular events after a stroke.

And they don't cause atrial fibrillation.

Or heart failure.

Or coronary heart disease in general. 

One of the common canards with the cholesterol confusionists is the claim that diet doesn't effect blood cholesterol that much.  As I've shown you already, this is only really true in diets that are already high in cholesterol.

CRP is like cholesterol in that if you already are inflamed or have high cholesterol, a diet that increases inflammation or cholesterol won't effect you much.  It should be noted that cholesterol itself increases inflammation.  Calorie restriction seems to help inflammation like it helps so many other metabolic problems, which is why some calorie restricted low carb studies seem to improve this biomarker.

Dietary choices can affect markers of inflammation.  Loren Cordain should know that red meat is specifically associated with C-reactive protein.

A low fat, vegan diet, however, dramatically lowers it.

It is true inflammation is important in heart disease, but this does not change the story on cholesterol.  High cholesterol and inflammation are partners in crime.

This leads me to a bigger issue, which I'll discuss in Part III.

Primitive Nutrition 45:
Anything but LDL, Part III

In my view, this argument that cholesterol levels are somehow less important than inflammatory markers raises a larger point.

This is an outstanding paper on the role of inflammation in atherosclerosis.  It is not appropriate to review it in a detailed way here.  These researchers are well aware that inflammation is important in the process of atherogenesis.  They show that our detailed understanding of atherosclerosis enabled by genetic research has illuminated the importance of inflammation as well as cholesterol.

Two of these researchers have written separately about the inflammatory process in atherosclerosis.  I just want use their graphics to illustrate how well atherosclerosis is understood now.

You can see that their description of the chain of events in its development is highly nuanced.

Here's the caption for that graphic.  Pause the video and read through it if you dare.  I find it comical that there are Crossfit trainers and exercise physiologists out there who think they understand the development of heart disease better than today's brilliant medical researchers.

Their narrative of how these plaques develop reflects our contemporary understanding. 

Read these few sentences and you can imagine all the research that has been done on cholesterol.  We're really getting into fine-grained detail.  These people are not misguided fools as Mark Sisson would you like to believe.

Here, for example, is a recent paper that has demonstrated in new detail how dietary cholesterol creates plaques.

New research into dietary cholesterol just makes it seem more and more guilty of hurting our health.

This knowledge has been facilitated by the exploding use of genetically altered lab animals, particularly mice and rats. 

Here you see that in rodents over 100 genes have been studied that influence the development of plaques.  Notice one of the researchers is Gregg Fonarow, the author of that paper about those first time heart attack sufferers, the one I talked about in Playing Games with Your Heart.  Maybe he knows what he's talking about a little better than broscientist Mark Sisson or comedian Tom Naughton.

Some of this transgenic research has demonstrated how much more important cholesterol is than triglycerides in causing heart disease.

Low carb apologists often complain that experimental animal models have their limitations in helping us understand heart disease in humans.  It’s a bit silly to read their protests that mice, for example, were not fed proper low carb diets, as if that makes any difference.  Researchers use these experiments to methodically examine every important variable they can imagine.  Do you remember when I introduced you to Anitschkow, the Russian pathologist who first induced atherosclerosis in rabbits with dietary cholesterol so long ago?  Even he understood that different animals processed cholesterol differently, and that they were all probably different than humans.

Even our closest primate relatives do not experience heart disease the same as us.

But the totality of the evidence is clear, and now that we are in the genetic age, it is ever more so.  Complaining that animals aren't good models for humans misses the forest for the trees.  My point here is that there is a huge body of knowledge behind current fat and cholesterol guidelines.  People who don't understand the science should at least understand their limitations and not attempt to contradict those who do know what they are talking about.

What has all this research taught us about biomarkers?  Well, total cholesterol is an excellent biomarker...

but nothing has yet upstaged good old LDL bad cholesterol.

The way lipoproteins work in the body is a very complicated business.  Chances are the information you see on the internet is seriously oversimplified.  We do need a way to measure what is happening in heart disease, and so far, the LDL score seems to tell us the most. 

This is because, unlike fibrinogen or CRP or any other particle that has been measured, LDL is the agent of damage to the artery.

Research with saturated fats fed to transgenic mice has demonstrated this.

As has research in humans.  Henry Buchwald has done remarkable work to clarify the importance of LDL.  Over a 25-year time frame, Dr Buchwald has shown through surgical bypass of the ileum, a procedure that forces the elimination of LDL from the body, he was able to reduce total and heart-related deaths, while not increasing the occurrence of cancer.

Steinberg, Interpretive History

The surgery worked because it caused the elimination of bile acids, removing cholesterol from the body.  Interestingly, dogs are great at converting cholesterol into bile acids for elimination, which is why they don't get heart disease. 

When bile acids are retained in humans, they result in elevated blood cholesterol.  Drugs have been used to prevent this from happening.

Ileal bypass was seen as a possible alternative to drugs for lowering LDL cholesterol many years ago.

Here you see Dr Buchwald's paper from 1990 at the outset of his study.  He believed his procedure would save lives because of its effect on LDL, and he was right.

Here is Dr Buchwald's paper from 2010 in which he announced his accomplishment.  Congratulations to him.

There is plenty of other research into LDL, of course.  Here it is shown that mutations in the LDL receptor are less important than LDL levels.  These mutations, of course, are what cause familial hypercholesterolemia.

The lowering of LDL levels has been shown to increase plaque stability, which Loren Cordain should like.

LDL was observed to be remarkably low in vegetarians long ago.  These numbers are amazing.

The body needs and uses LDL, of course, but it makes all it needs without a diet that adds more.

Still, LDL is not a perfect surrogate for heart disease risk.  In the context of drug trials, it is now known that some drugs can lower LDL dramatically without a corresponding reduction in cardiovascular events. 

However, LDL still seems to be the best way of identifying people at risk at the moment.  Don't misunderstand my argument in this video.  All these biomarkers give doctors valuable information that helps them determine the best treatments for their patients.  All I'm saying is, don't let someone distract you with this stuff so that you can more easily rationalize eating an unhealthy diet.  I think it's pretty interesting that the most important risk factor for heart disease, high LDL, is the one low carb diets can't seem to improve unless calories get super low.

What matters more than biomarkers is the risk of cardiac events.  Dean Ornish has already shown that this can be improved with the help of a healthy diet.  This study made him famous.

Ornish was able to regress heart disease and reduce cardiac events among his study subjects even though his diet raised their triglycerides.  Should this be viewed as a failed study because their triglycerides went up?  Or should this caution us about misunderstanding triglycerides?

It shouldn't have been surprising that Ornish could do this with diet. Atherosclerosis had been turned back in animals many times.  Here you see that vervet monkeys developed atherosclerosis on a diet of entirely normal western foods.  A realistic healthier diet was able to regress these plaques a little.  Ornish just used a more aggressive diet.

Here macaques responded this way as well.  On the left side of both graphs you see that atherosclerosis escalated on a high cholesterol, high saturated fat diet.  To the right you see a regression of the atherosclerosis took place when either the diet was changed to alfalfa meal or after a cholesterol-lowering drug was administered.

We know now that plant foods can regress heart disease.

Don't fruit and berries sound like a rather enjoyable therapy?

By contrast, nutrient-poor, meat-heavy diets are associated with advancing atherosclerosis.  Let's be clear that this is not health food.

I have shown you that all these biomarkers may reflect reverse causation, or may not be informative in some cases, or are not preferable to LDL.  More importantly, I have also shown you that all of these biomarkers can be brought within their target ranges through a plant-based diet.  Often the benefits of statins are explained away by cholesterol deniers as the result of other effects they have beside cholesterol lowering, but doesn't it make sense that all risk factors should improve as heart disease is healed?  And doesn't it also make sense to use diet to accomplish this instead of drugs?

If you unwisely choose to reject what the confusionists call the conventional wisdom, which is just a weasely way of saying the accumulated knowledge of medical science, they will not be there for you when you have a cardiac event.  They want page views and sales for their products today.  They won't be there to pay your medical bills or support your family when you have a serious health problem.  If you require hospitalization you will then be in the medical system, and you will be given medication that is not based on conventional wisdom or bias but on the real knowledge and experience of medical professionals, and they will give you targeted therapies to try to help you.  You will almost certainly be put on cholesterol-lowering medication, and your quality of life will be worse, and that will be if you are lucky.

My advice to you, if you will consider it, is to abandon internet nonsense and take care of your health through diet while you are healthy.  Whole plant foods will help you do this, and probably for less money than you spend on food right now.  

Don't those berries look delightful?  Yet there is a diet out there that tries to make an enemy of colorful fruits like these.  It's a diet where colors are less vibrant and flavors are never naturally sweet.  It's a diet that is heavy and gray.  It's the gloomiest diet, next in the Primitive Nutrition Series.