The Straight Dope on Cholesterol: 10 Things You Need to Know – Part 1
This is a guest post by Peter Attia and is a summary based on a 10-part series of the same name that you can find at The Eating Academy.
To put this summary post and, more importantly, this 10-part series in perspective, let’s examine one of the most pervasive pieces of dietary advice given to people worldwide:
“Eating foods that contain any cholesterol above 0 mg is unhealthy.”
- T. Colin Campbell, PhD, author of The China Study.
No summary of this length can begin to fully address a topic as comprehensive as cholesterol metabolism and the pathogenesis of atherosclerosis. In fact, those of us who challenge conventional wisdom often find ourselves needing to do exactly what Frederic Bastiat suggested:
“We must admit that our opponents in this argument have a marked advantage over us. They need only a few words to set forth a half-truth; whereas, in order to show that it is a half-truth, we have to resort to long and arid dissertations.”
So, at the risk of trying to minimize the “long and arid” part of this process, below are the 10 things you need to know to be the judge – for yourself – if the conventional advice about cholesterol is correct.
1. The sine qua non of atherosclerosis is the presence of a sterol in an artery wall. How it gets there is the only thing we should be worrying about.
Contrary to popular belief, atherosclerosis is not caused by many of things we think of, such as smoking, high blood pressure, diabetes, high LDL (the so-called “bad” cholesterol), or low HDL (the so-called “good” cholesterol). Some of these are certainly markers of risk – low HDL, for example – while others accelerate the process – smoking, for example – but none of these are the direct cause of atherosclerosis.
The sine qua non of atherosclerosis is the presence of sterols (cholesterol or phytosterol) in arterial wall macrophages. Sterols are delivered to the arterial wall by the penetration of the endothelium by an apoB-containing lipoprotein, which transport the sterols. In other words, unless an apoB-containing lipoprotein particle violates the border created by an endothelium cell and the layer it protects, the media layer, there is no way atherogenesis occurs. If this is a bit confusing, don’t worry. It’s all made clear below.
2. Cholesterol is vital for life; no cholesterol = no life.
Cholesterol is a 27-carbon molecule shown in the figure below. Each line in this figure represents a bond between two carbon atoms. That’s it. Mystery over.
All this talk about “cholesterol” and most people don’t actually know what it is. So, there you have it. Cholesterol is “just” another organic molecule in our body.
I need to make one distinction that will be very important later. Cholesterol, a steroid alcohol, can be “free” or “unesterified” (“UC” as we say, which stands for unesterified cholesterol) which is its active form, or it can exist in its “esterified” or storage form which we call a cholesterol ester (“CE”). The diagram below shows a free (i.e., UC) molecule of cholesterol. An esterified variant (i.e., CE) would have an “attachment” where the arrow is pointing to the hydroxyl group on carbon #3, aptly named the “esterification site.”
One of the biggest misconceptions is that cholesterol is “bad.” This could not be further from the truth. Cholesterol is very good! In fact, there are (fortunately rare) genetic disorders in which people cannot properly synthesize cholesterol. One such disease is Smith-Lemli-Opitz syndrome (also called “SLOS,” or 7-dehydrocholesterol reductase deficiency) which is a metabolic and congenital disorder leading to a number of problems including autism, mental retardation, lack of muscle, and many others.
Cholesterol is absolutely vital for our existence. Every cell in our body is surrounded by a membrane. These membranes are largely responsible for fluidity and permeability, which essentially control how a cell moves, how it interacts with other cells, and how it transports “important” things in and out. Cholesterol is one of the main building blocks used to make cell membranes (in particular, the ever-important “lipid bilayer” of the cell membrane).
Beyond cholesterol’s role in allowing cells to even exist, it also serves an important role in the synthesis of vitamins and steroid hormones, including sex hormones and bile acids. Make sure you take a look at the picture of steroid hormones synthesis and compare it to that of cholesterol (above). If this comparison doesn’t convince you of the vital importance of cholesterol, nothing I say will.
One of the unfortunate results of the eternal need to simplify everything is that we (i.e., the medical establishment) have done the public a disservice by failing to communicate that there is no such thing as “bad” cholesterol or “good” cholesterol. All cholesterol is imperative for life to exist!
The only “bad” outcome is when cholesterol ends up inside of the wall of an artery, most famously the inside of a coronary artery or a carotid artery, AND leads to an inflammatory cascade which results in the obstruction of that artery (make sure you check out the pictures in the links above). When one measures cholesterol in the blood we really do not know the final destination of those cholesterol molecules!
3. The cholesterol we eat has little to do with the cholesterol we measure in our bloodstream.
We ingest (i.e., take in) cholesterol in many of the foods we eat and our body produces (“synthesizes”) cholesterol de novo from various precursors. About 25% of our daily “intake” of cholesterol – roughly 300 to 500 mg – comes from what we eat (called exogenous cholesterol), and the remaining 75% of our “intake” of cholesterol – roughly 800 to 1,200 mg – is made by our body (called endogenous production). To put these amounts in context, consider that total body stores of cholesterol are about 30 to 40 gm (i.e., 30,000 to 40,000 mg) and most of this resides within our cell membranes. Nearly every cell in the body can produce cholesterol, and thus very few cells actually require a delivery of cholesterol. Cholesterol is required by all cell membranes and to produce steroid hormones and bile acids.
Of this “made” or “synthesized” cholesterol, our liver synthesizes about 20% of it and the remaining 80% is synthesized by other cells in our bodies. The synthesis of cholesterol is a complex four-step process (with 37 individual steps) that I will not cover here, but I want to point out how tightly regulated this process is, with multiple feedback loops. In other words, the body works very hard (and very “smart”) to ensure cellular cholesterol levels are within a pretty narrow band (the overall process is called cholesterol homeostasis). Excess cellular cholesterol will crystalize and cause cellular apoptosis (programmed cell death). Plasma cholesterol levels (which is what clinicians measure with standard cholesterol tests) often have little to do with cellular cholesterol, especially artery cholesterol, which is what we really care about. For example, when cholesterol intake is decreased, the body will synthesize more cholesterol and/or absorb (i.e., recycle) more cholesterol from our gut. The way our body absorbs and regulates cholesterol is really amazing, so I want to spend a bit of time discussing it.
- The blue circle in this figure represents something called a Niemann-Pick C1-like 1 protein (NPC1L1). It sits at the apical surface of enterocytes and it promotes active influx (i.e., bringing in) of gut luminal unesterified cholesterol (UC) as well as unesterified phytosterols into the enterocyte. Think of this NPC1L1 as the ticket-taker at the door of the bar (where the enterocyte is the “bar”); he lets most cholesterol (“people”) in. However, NPC1L1 cannot distinguish between cholesterol (“good people”) and phytosterol (“bad people” – for reasons I won’t discuss here) or even too much cholesterol (“too many people”).
- The pink circle in this figure represents a structure called the adenosine triphosphate (ATP)-binding cassette (ABC) transporters ABCG5 and ABCG8. This structure promotes active efflux (i.e., kicking out) of unesterified sterols (cholesterol and plant sterols – of which over 40 exist) from enterocytes back into the intestinal lumen for excretion. Think of ABCG5/G8 as the bouncer at the bar; he gets rid of the really bad people (e.g., phytosterols, as they serve no purpose in humans) you don’t want in the bar who snuck past the ticket-taker (NPC1L1). Of course, in cases of hyperabsorption (i.e., where the gut absorbs too much of a good thing) they can also efflux out un-needed cholesterol. Along this analogy, once too many “good people” get in the bar, fire laws are violated and some have to go. The enterocyte has “sterol-excess sensors” (a nuclear transcription factor called LXR) that do the monitoring, and these sensors activate the genes that regulate NPC1L1 and ABCG5/G8.
There is another nuance to this, which is where the CE versus UC distinction comes in:
- Only free or unesterified cholesterol (UC) can be absorbed through gut enterocytes. In other words, cholesterol esters (CE) cannot be absorbed because of the bulky side chains they carry.
- Much (> 50%) of the cholesterol we ingest from food is esterified (CE), hence we don’t actually absorb much, if any, exogenous cholesterol (i.e., cholesterol in food).
- Furthermore, most of the unesterified cholesterol (UC) in our gut (on the order of about 85%) is actually of endogenous origin (meaning it was synthesized in bodily cells and returned to the liver), which ends up in the gut via biliary secretion and ultimately gets re-absorbed by the gut enterocyte. The liver is only able to efflux (send out via bile into the gut) UC, but not CE, from hepatocytes (liver cells) to the biliary system. Liver CE cannot be excreted into bile. So, if the liver is going to excrete CE into bile and ultimately the gut, it needs to de-esterify it using enzymes called cholesterol esterolases which can convert liver CE to UC.
4. The cholesterol in our bloodstream has little to do with the cholesterol in our artery walls (i.e., atherosclerosis).
To understand how cholesterol travels around our body requires some understanding of the distinction between hydrophobic and hydrophilic. A molecule is said to be hydrophobic (also called nonpolar) if it repels water, while a molecule is said to be hydrophilic (also called polar) if it attracts water. Think of your veins, arteries, and capillaries as the “waterways” or rivers of your body. Cholesterol is precious “cargo” that needs to move around, but it needs a “boat” to carry it.
The proteins that traffic collections of lipids are called apoproteins. Once bound to lipids they are called apolipoproteins, and the protein wrapped “vehicle” that transports the lipids are called lipoproteins. Many of you have probably heard this term before, but I’d like to ensure everyone really understands their important features. A crucial concept is that, for the most part, lipids go nowhere in the human body unless they are a passenger inside a protein wrapped vehicle called a lipoprotein. As their name suggests, lipoproteins are part lipid and part protein. They are mostly spherical structures which are held together by a phospholipid membrane (which, of course, contains free cholesterol). The figure below shows a schematic of a lipoprotein.
You will also notice variable-sized proteins on the surface of the lipid membrane that holds the structure together. The most important of these proteins are called apolipoproteins, as I alluded to above. The apolipoproteins on the surface of lipoprotein molecules serve several purposes including:
- Assisting in the structural integrity and solubility of the lipoprotein;
- Serving as co-factors in enzymatic reactions;
- Acting as ligands (i.e., structures that help with binding) for situations when the lipoprotein needs to interact with a receptor on a cell.
Apolipoproteins come in different shapes and sizes which determine their “class.” Without getting into the details of protein structure and folding, let me focus on two important classes: apolipoprotein A-I and apolipoprotein B. ApoA-I is the apolipoprotein that wraps HDL particles. ApoB is the apolipoprotein that wraps VLDL, IDL, and LDL particles.
5. The only way sterols end up in artery walls – the one place we don’t want them to be – is if the sterols are carried there by an apoB-containing lipoprotein particle.
So what drives a LDL particle to do something as sinister as to leave the waterway (i.e., the bloodstream) and “illegally” try to park at a dock (i.e., behind an endothelial cell)? Well, it is a gradient driven process which is why particle number is the key driving parameter.
As it turns out, this is probably a slightly less important question than the next one: what causes the LDL particle to stay there? In the parlance of our metaphor, not only do we want to know why the boat leaves the waterway to illegally park in the dock with its precious cargo, but why does it stay parked there? This phenomenon is called “retention” in lipidology-speak.
Finally, if there was some way a LDL particle could violate the endothelium, AND be retained in the space behind the cell (away from the lumen on the side aptly called the sub-endothelial space) BUT not elicit an inflammatory (i.e., immune) response, would it matter?
I don’t know. But it seems that not long after a LDL particle gets into the sub-endothelial space and takes up “illegal” residence (i.e., binds to arterial wall proteoglycans), it is subject to oxidative forces, and as one would expect an inflammatory response is initiated. The result is full blown mayhem. Immunologic gang warfare breaks out and cells called monocytes and macrophages and mast cells show up to investigate. When they arrive and find the LDL particle, they do all they can to remove it. In some cases, when there are few LDL particles, the normal immune response is successful. But, it’s a numbers game. When LDL particle invasion becomes incessant, even if the immune cells can remove some of them, it becomes a losing proposition and the actual immune response to the initial problem becomes chronic and maladaptive and expands into the space between the endothelium and the media.
The multiple-sterol-laden macrophages or foam cells coalesce, recruit smooth muscle cells, induce microvascularization, and before you know it complex, inflamed plaque occurs. Microhemorrhages and microthrombus formations occur within the plaque. Ultimately the growing plaque invades the arterial lumen or ruptures into the lumen inducing luminal thrombosis. Direct luminal encroachment by plaque expansion or thrombus formation causes the lumen of the artery to narrow, which may or may not cause ischemia.
Check back tomorrow for Part 2 of The Straight Dope on Cholesterol: 10 Things You Need to Know
Posted By: Mark Sisson
These are the articles I want to read: facts, real results of real researches. I’m looking forward to reading the second part.
This is GOOD stuff. Please more!
I was literally shocked to see a front page headline in the UK yesterday claiming that everyone over the age of 50 should be taking statins! An Oxford University professor who has conducted a major study into cholesterol made this claim. Can you imagine? your health can only be secured by taking drugs every day? DISGUSTING!!!
http://www.dailymail.co.uk/health/article-2194892/All-50s-statins-regardless-health-history-says-Oxford-professor.html
From the article, it seems that this recommendation is not the LAW yet but it may be if the government takes over our healthcare in this country, see Obamacare!
Yes, Eva, you are so right.
They are all dead there. No people in Sweden, no people in France (wow, Champs-Élysées can be mine), no people in Canada, etc.
Horror, horror everywhere.
I lived in socialized medicine country for 30 years and you would not like it. To get care, you would need to bribe a doctor!
Choices and de-centralization of decision making are safe…
When there is no competition and fee enterprise, nothing works…
And which socialized medicine country do you have in mind, Eva? The former Soviet Soviet Union, by any chance? East Germany? Is it possible that there are structural differences between the FSU and let’s say … France?
“When there is no competition and fee enterprise, nothing works…”
Yes, Eva, some of us (I hope most) need this high quality lecture. Yeah. Sure.
dr anna
dr anna,
You caught me on dropping the R. It was to be “free enterprise,” of course…
You knew what I meant.
Most people would agree it’s true that a competition (see Olympics) and free enterprise (see the last 200 years in this country alone) are the most dynamic force in any activity… in health care or elsewhere…
And we all benefit from it.
:=)
Eva
“Most people would agree it’s true that a competition (see Olympics) and free enterprise (see the last 200 years in this country alone) are the most dynamic force in any activity… in health care or elsewhere…
And we all benefit from it.
:=)”
Yeah, life is simple. Eva, can I recommend that you open some decent book of history before … babbling?
Yes, I can see the last 200. Hmmm – yes, I see slavery (it was free enterprise), elimination of many Indian tribes (as part of free enterprise), extermination of a significant portion of every immigration group in the past (before the New Deal) and increasingly again ( after the New Deal), etc.
How people can spend their lives on the level of propaganda and demagoguery is beyond me.
To repeat my comment:
I’d just like to point out that here in the UK, with the NHS, we still have a CHOICE as to whether we access/use the treatments recommended to us by our FREE GPs. We’re not forced to take drugs we don’t want. We may be recommeded to do so, but we have every right to not pick up the prescription if we don’t want to, and we have every right to look for alternative treatment if we want, including via private health insurance.
FREE HEALTHCARE is NOT evil, bad or wrong in any way. Instead it allows millions of people who are otherwise too poor to access the same level of care as everyone else in their society.
Eva,
Please cease and desist with the Obamacare. Go to a political blog. This is not the place, and it is becoming annoying.
Thank you, Mark, for a well written explanation of the cholesterol scam. I always try to calm our patients down following their primary care doctor diagnosing them with elevated total or LDL cholesterol levels. Endothelial damage from lipid oxidation is the demon, rather than arterial plaque deposition of cholesterol. Cholesterol is merely the patching material to repair oxidation. Homocysteine, an amino acid present at the site of oxidation is really the villain. The problem is that the pharmaceutical industry does not have a homocysteine lowering drug, but they do have statin class of drugs which blocks the liver’s production of cholesterol. Every hormone made in the body is based on cholesterol, which is why liver enzyme status is monitored so closely. It is better to regiment your diet with a rainbow of fruits and vegetables to reduce free radical damage.
Thanks Marc- this is useful advice. I’m going to look for research on homocysteine now- appreciate the tip!
Apparently the vitamins B are the ticket for scrubbing homocysteine – particularly B6, B12 and folic acid (although taking the whole vitamin B complex is probably a good idea.. there are a couple of the B’s that can cause a deficiency if one is taken to excess without the other (I think the pair is B3 and B6, but check this, I’m going from memory).
Great article, I’ve learned a lot here. Every hormone, food and everything has 2 sides and a lot more functions than people are aware of.
Hey, we can half truth it too! Anything which wasn’t eaten 60k years ago is unhealthy. See? It’s half right but completely excludes things like kombucha and cod liver oil.
I am hearing mixed messages. On one hand, cholesterol is not bad, it is good. On the other hand, I see many articles here on how to lower cholesterol. So if it is not bad, why worry about lowering it? See how confusing this is?
I just found this out and wanted to share. High cholesterol MAYBE due to the thyroid dysfunction. See below:
“Fewer than half of the adults who had been diagnosed with high cholesterol know if they had ever been tested for thyroid disease, despite the well-documented connection between the two conditions.
Ninety percent of those surveyed were unaware of the thyroid gland’s impact on cholesterol regulation.
According to AACE President Richard A. Dickey, M.D., “Patients who have been diagnosed with high cholesterol should ask their physician about having their thyroid checked. If they have an underlying thyroid condition in addition to their high cholesterol, the cholesterol problem will be difficult to control until normal levels of thyroid hormone are restored.”
Just found out and want to share.
High cholesterol MAY BE due to the thyroid malfunctioning. See below:
“Fewer than half of the adults who had been diagnosed with high cholesterol know if they had ever been tested for thyroid disease, despite the well-documented connection between the two conditions.
Ninety percent of those surveyed were unaware of the thyroid gland’s impact on cholesterol regulation.
According to AACE President Richard A. Dickey, M.D., “Patients who have been diagnosed with high cholesterol should ask their physician about having their thyroid checked. If they have an underlying thyroid condition in addition to their high cholesterol, the cholesterol problem will be difficult to control until normal levels of thyroid hormone are restored.”
You bring up a good point. Someone else in the paleo blogosphere wrote a thorough write-up on the that and the mechanism is roughly as follows. Not enough iodine -> Low thyroid activity -> LDL receptors don’t absorb the LDL particles in your bloodstream -> LDL particles stay in the blood longer, giving a larger LDL number on your blood test, lowering bile acid production and digestion, lowering sex hormone production and libido
Eat your seaweed or get enough iodine any way you can.
I know about iodine and just tested this theory on my relative and it did not work. We suspect the Hashimoto’s disease in which case when the thyroid gland is damaged, no stimilation will help, unfortunately… We will do more tests:
-antibodies against thyroglobulin (TG) and
- thyroid peroxidase (TPO),
both detected via blood test.
If positive, then only taking RX is an option: either the synthetic thyroid hormone or from a pig thyroid called Armour Thyroid. There are no side effects from either but a patient must be monitored by a simply blood test for TSH (or also for T3 and T4 hormones) at least every 6 months. VERY important!
I would pick the natural RX but the only problem with it that the amount of the thyroid hormone is NOT precisely accurate in the pig derivative…
Mark Sisson quoting Bastiat! Me thinks Lew Rockwell is rubbing off on you.
I would very much like to see a study of smokers who exercise and follow a paleo/ PBP diet.
Reply to:
“I would very much like to see a study of smokers who exercise and follow a paleo/ PBP diet.”
Do these people exist? Can even smokers exercise? They probably cannot get up the stairs (after some time of smoking)!! If you you are paleo, you will not put these harmful chemicals into your body understanding how it works, right?
I have a daughter who started smoking at 14 and there was nothing we could do. Now she is 28 with a thyroid problem. Of course, we do not know if smoking have caused it but I always say to her: NOBODY CAN BE HEALTHY WHILE PUMPING TOXINS INTO HIS/HER BODY, period.”
I tend to differ slightly on meats that are high in cholesterol. If an animal has high cholesterol from being grainfed the meat contains many toxins. Therefore meats high in cholesterol should be avoided because of the toxins, not the cholesterol. Like humans, the cholesterol is an indicator the animal is not healthy and should not be consumed.
I was diagnosed with Primary Biliary Cirrhosis about 12 years ago, an autoimmune disease that causes fibrosis of the small bile ducts. My gastro doc tells me that this causes my liver to not metabolize cholesterol well, causing me to have a relatively high (230) blood cholesterol level. I have been resisting his advice to go on statins. I always thought I was a healthy eater, but until recently ate a lot of grains. Does anyone know the relationship between liver disease and artherosclerosis, and whether the cholesterol that is spit out by my liver into my bloodstream really makes a difference? Does the fact that I obviously have issues with inflammation make me more prone to plaque buildup? Any links to research on this would be appreciated.
Check out the med references in WHEAT BELLY about grains’ impact on insulin metabolism and cholesterol, among other things. Lots of grains = carbo overload = mucked up metabolism.
I doubt if your gastro doc recommended your thyroid check. Did he? Let me know, please.
I have a problem with so many docs. They do not see beyond their specialty.
We need more like Dr. Mercola who has been my mentor for over a decade.
Eva
Great info! But not an easy read. I gotta bookmark this baby and come back and study!
Awesome post as always. Now I have to go and translate this to my father who has a very high cholesterol. Finally I can’t tell him not to be afraid of eggs.
So the medical/pharmacological dictate is based on lies, so we can’t trust them, nor can we trust our doctors, who are forced to practice according to these lying and false dictates. So we have to learn more than the doctors are taught, ignore the doctors advice, and learn the truth through long and arid dissertations. Well, I’ll try my best, but I did not take organic chemistry and this stuff makes my head hurt.
What my pea brain can understand is that if you are over 50 and have a lower than normal serum cholesterol level, you have a higher chance of dying from heart disease. That fact alone tells me they (big pharma/medicine) are up to no good and don’t have my best interests at heart, despite what they say. Thanks for the information. This heavy lifting is harder than the pullups – HA!
Lecithin (the solvent for cholesterol)and magnesium are the key to preventing artery disease. A protocol of calcium, magnesium, and lecithin will clean out your arteries like several of my friends have proved, and one verified with an angiogram. See Adel Davis’: Let’s Get Well. The body plugs the leaks with cholesterol, and lecithin gradually removes it. If you aren’t getting enough, the body covers the lesion with calcium.
Very interesting material… I’ll forward to some friends and family who will neither read it nor listen when I discuss it… hey, I tried.
Thanks to Stickwick from VP blog for recommending this place… I can see there’s a lot of good info to absorb here.
For those trying to bring politics into this, allow me to offer a reality check. The powerful elites will do whatever they decide to do and the ignorant masses will praise their “vision” and “leadership” while marching into the mass graves, pill bottles in hand… you can do NOTHING to change that.
Stay on point about the nutrition issues and focus on living as well as you’re allowed to, then dying honorably. Everything else is a waste of effort.
Like I pointed out before, cholesterol level has to do with our thyroid
function. Therefore, when cholesterol is elevated, it is a good idea to check
what thyroid’s numbers are (TSH, T3 and T4).
But there is more to it. All our systems are connected and depend on
each other. Now, the thyroid health relies on our digestive system:
gut and liver in particular.
I get emails from a lady who is not an M.D, but calls herself a “thyroid
coach” and knows this topic. I do not know her personally.
She sent me a link to her new Video Class #1, where you will learn:
The role of the digestive system in thyroid health.
What digestive issues you should be worried about.
What the liver does for your thyroid.
How to know if you need to cleanse your gut and your liver, and
How toxicity slows down your thyroid.
I see that her main theme here is detoxification, “cleaning house.”
I am going to watch it to learn from it:
http://thyroiddetox.com/?utm_source=Thyroid%20Diet%20Coach%20Master%20List&utm_campaign=c0d970d35d-TD_Video_19_3_2012&utm_medium=email
Eva
I recently dealt with a bizar drop in red and white blood cell count, and increased cholesterol. The cause has yet to be determined, but interestingly when my anemia (low red blood cell count) and lukocytopenia (low white blood cell count) came back to normal range, my cholesterol levels balanced out as well. Perhaps the cholesterol was high due to a diminished WBC count. Anyway, I learned a TON in this post.
Next book to tackle which speaks about cholesterol is “Good Calorie, Bad Calorie”.
It is actually a nice and helpful piece of info. I am glad that you simply shared this helpful info with us. Please stay us up to date like this. Thanks for sharing.
At age 42 i have already had a 5 way bypass due to 4 blockages and 5 years later had a stent placed, what can i do to reduce the LDL which is higher than my HDL im already on Liptor. Thanks Mike