To read more about heart disease and cholesterol, check out this eBook on the Diet–Heart Myth.
Cardiovascular disease is one of the most misdiagnosed and mistreated conditions in medicine. In the first article in this series, I explained the evidence suggesting that eating cholesterol and saturated fat does not increase cholesterol levels in the blood for the majority of the population.
In this article, I will debunk the myth that high cholesterol in the blood is the cause of heart disease.
Myth #2: High Cholesterol Is the Cause of Heart Disease
Part of the confusion about cholesterol and its role in heart disease is caused by imprecise terminology. So, before I explain why high cholesterol is not the underlying cause of heart disease, we have to cover some basics.
In order for cholesterol to be transported around the body in the blood, it has to be carried by special proteins called lipoproteins. These lipoproteins are classified according to their density; two of the most important in heart health and cardiovascular disease are low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
I know this can get confusing quickly, so let me use an analogy to make this more clear. Imagine your bloodstream is like a highway. The lipoproteins are like cars that carry the cholesterol and fats around your body, and the cholesterol and fats are like passengers in the cars. Scientists used to believe that the number of passengers in the car (i.e. concentration of cholesterol in the LDL particle) is the driving factor in the development of heart disease. More recent studies, however, suggest that it’s the number of cars on the road (i.e. LDL particles) that matters most.
The crucial test for heart disease risk you’ve probably never heard of.
Coronary arteries are essentially hollow tubes, and the endothelium (lining) of the artery is very thin—only one cell deep. The blood, which carries lipoproteins like LDL, is in constant contact with the endothelial lining. So why does the LDL particle leave the blood, penetrate the endothelium and enter the artery wall? The answer is that it’s a gradient-driven process. Going back to our analogy, the more cars there are on the road at one time, the more likely it is that some of them will “crash” into the fragile lining of the artery. It’s not the number of passengers (cholesterol) the cars are carrying that is the determining factor, but the number of cars on the highway.
The significance of this in terms of determining your risk of heart disease is profound. When you go to the doctor to get your cholesterol tested, chances are he or she will measure your total, LDL and HDL cholesterol. This tells you the concentration of cholesterol (passengers) inside of the lipoproteins (cars), which is not the driving factor behind plaque formation and heart disease. Instead, what should be measured is the number of LDL particles in your blood.
LDL cholesterol levels and LDL particle number are often concordant (i.e. when one is high, the other is high, and vice versa), and this is probably why there is an association between LDL cholesterol and heart disease in observational studies. The elevated LDL cholesterol was more of a proxy marker for elevated LDL particle number in these cases. But here’s the kicker: they can also be discordant. In layperson’s terms, it’s possible to have normal or even low cholesterol, but a high number of LDL particles. (1) If this person only has their cholesterol measured, and not their particle number, they will be falsely led to believe they’re at low risk for heart disease. Even worse, the patients that are the most likely to present with this pattern are among the highest risk patients: those with metabolic syndrome or full-fledged type 2 diabetes.
On the other hand, patients with high LDL cholesterol (LDL-C) and low LDL particle number (LDL-P) are not at high risk of heart disease. In fact, studies suggest they’re at even lower risk than patients with low LDL-C and low LDL-P. (3) Yet they will often be treated with statin drugs or other cholesterol lowering medications, because the clinician only looked at LDL-C and failed to measure LDL particle number. This is a concern for two reasons. First, statin drugs aren’t harmless. (I’ll go into more detail on this in the third post of the series.) Second, studies suggest that low cholesterol can increase the risk of death, especially in women and the elderly.
In one study of over 52,000 Norwegians, researchers found that women with total cholesterol levels below 195 mg/dL had a higher risk of death than women with cholesterol levels above that cut-off. (4) And a study published in the American Journal of Medicine found that people over 70 years of age with total cholesterol levels below 160 mg/dL had twice the risk of death than those with cholesterol levels between 160-199 mg/dL. (5) Low cholesterol is also associated with increased risk of disease—especially mental health and brain disorders. For example:
- A study in the Journal of Psychiatric Research found that men with low total cholesterol levels were 7 times more likely to die prematurely from unnatural causes such as suicide and accidents than other men in the study. (6)
- A 1993 study published in The Lancet found that depression was 3 times more likely in men over 70 with low cholesterol than in those with normal or high cholesterol. (7)
- A Swedish study found that women with the lowest cholesterol suffered significantly more depressive symptoms than other women in the study. (8)
- A study in the journal Neurology showed that low cholesterol is associated with increased risk of dementia. (9)
- A paper published in the European Journal of Internal Medicine linked low cholesterol levels with Alzheimer’s disease. (10)
It’s important to note that all of these studies were observational, which means that they don’t prove that low cholesterol was the cause of the increased risk of death or disease that was observed. It’s possible, for example, that these patients had another disease that caused both the lower cholesterol and increase in disease or mortality. However, given what we know about the important roles of cholesterol in the body, it’s certainly plausible that low cholesterol is capable of contributing to these problems directly.
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Wrapping Up: The Map Is Not the Territory!
Before concluding, I’d like to point out that although LDL particle number is superior to LDL cholesterol as a marker for heart disease, it’s still just that—a marker. A marker is not a disease. It’s a risk factor for a disease. Having a risk factor for a disease does not guarantee that you will get that disease—it just increases the chance that you will. There are still several gaps in our knowledge about LDL-P and its usefulness in a clinical setting. For example:
- Imagine two people with an LDL-P above 2,000, which puts them in the highest risk group. Person A follows a Paleo diet and lifestyle, gets plenty of sleep, manages stress and has no other significant risk factors for heart disease. Person B eats a Standard American Diet, doesn’t exercise, doesn’t get enough sleep, is stressed out and has several other risk factors for heart disease. Logic would dictate that Person A would be at much lower risk for heart disease than Person B, but there isn’t any comparative data to quantify the difference in risk and it’s unlikely such a study will ever be done. (Who would pay for it?)
- Imagine two people following a healthy Paleo-type diet and lifestyle. Person C has no conventional risk factors for heart disease. Person D has no conventional risk factors either, but does have an LDL-P of 2,000. Logic here would dictate that Person D is at higher risk than Person C, but again, we don’t have actual data to quantify the difference in risk.
Heart disease is a complex, multifactorial process. The likelihood that we’ll have a heart attack depends on numerous factors, including genetics, diet, lifestyle and living environment. The purpose of this article is not to suggest that LDL-P is the only risk factor that matters, or that other risk factors shouldn’t be taken into consideration. It is simply to point out that existing evidence suggests that LDL-P is a much better predictor of heart disease risk than LDL or total cholesterol, and that it appears to be one of the better markers available to us now.
Want to learn more? Check out my next article in the series “What Causes Elevated LDL Particle Number?“, followed by “Statins Don’t Save Lives in People Without Heart Disease.”
Note: if you’re interested in a much more thorough discussion of how to determine your risk of heart disease and how to use diet, supplements and lifestyle changes to protect yourself and those you love, check out the High Cholesterol Action Plan.
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Hi
Where can I get a VAP lipd test in the UK or do I have to travel to USA to obtain such a test ?
just read an article about the Farmingham study that stated folks with overall cholesterol levels less than 150 had virtually no heart attacks . That seems to contradict the above article . Please Explain
When we take liposomal Vitamin C or other liposomal products, does this also increase the cars in the blood that may lead the LDL cars to more likely drive through the artery wall, or are we talking about two unrelated kinds of traffic? Thank you.
So, here’s what I’m really interested to see for us non-technical people who are just looking to make sense of our numbers and look at it different than our non-Paleo docs: A straightforward list of the factors and the numbers that are acceptable. I understand the relationship to TSH and T3 T4, and Trigs, and the ratio of HDL:LDL, and the better predictive factor or LDL-P number – but I haven’t seen a list of what ARE healthy ranges of these numbers. Am I missing it somewhere?? Help!
Hi Chris
Is there a formula for converting ApoB concentration into LDL-P particle number, maybe taking TGs into account? Also, what are the typical ApoB and LDL-P percentiles?
Chris – Thanks for your great work.
This series comes at a critical time for me as my dad had heart issues earlier in the week. I haven’t talked to the docs yet, but was told his heart is very weak and he has “cardiomyopathy”. Will be meeting the docs this week hopefully to find out more.
I already know it will be a battle with him and the docs. 1st things I found upon arriving tonight (I live on the other side of the world) is a tube of fake fat which he was told to have instead of butter. Meanwhile loaves of white bread and sugar are fine! I may fill the tube with quality butter or lard and just not tell him.
p.s. this is the junk they recommend:
Promise Spread: Vegetable Oil Blend (Liquid Soybean Oil, Canola Oil, Palm Oil, Palm Kernel Oil), Water, Whey (Milk), Salt, Vegetable Mono and Diglycerides, Soy Lecithin, (Potassium Sorbate, Calcium Disodium EDTA) Used to Protect Quality, Vitamin E Acetate, Citric Acid, Pyridoxine Hydrochloride (Vitamin B6), Artificial Flavor, Maltodextrin (Corn), Vitamin A Palmitate, Beta Carotene (Color), Cholecalciferol (Vitamin 13), Cyanocobalamin (Vitamin B12).
Hi Chris (and previous poster Sean)
I’m in a similar situation to Sean in that my Dad three years ago had a heart attack and had two stents put in, as one thing was 100% blocked and another 90%. He has ‘high’ blood cholesterol in the family but I’m unsure if that is the Familial Hypercholesterolemia that you talk about. You seem to have different dietary recommendations for the latter and it has left me a little confused. Will you be doing a blog post about how to deal with Familial Hypercholesterolemia?
I’m afraid of broaching this topic with my parents as they have for many years followed the notion that low-fat anything is good, margarine is good and butter is bad, whole-grain muesli and bread are fantastic, and they both love biscuits and jam, etc as well as a daily coffee.
I don’t want my Dad to have another heart attack. What on earth do I do.
Patrick – Great to hear from someone else with similar experiences. Though our fathers are in different situations. Still love to hear more on this. Looking forward to the rest of this series!
Regarding my father:
– I suspect viral infection causing cardiomyopathy
Here’s why:
– He was sick 4 weeks before entering the hospital (suspected extreme flu though never visited the doctor). From then, until entering the hospital, he began to lose sleep to the point of absolutely no sleep for more than a week, often couldn’t breath and had extreme water retention. Drove himself to the ER! They immediately diagnosed congestive heart failure (which can mean many things). They said he came just in time before a heart attack or worse.
Based on research relating to cardiomyopathy, I’m thinking it could have been a viral infection.
More background:
– Age: 53
– Is not sedentary (active job)
– No family history of heart issues
– Smoked his whole life, but his lungs were perfectly clear
– Left heart cath: no blockages, no stents
– No cholesterol issues. Blood pressure is fine. Everything is healthy with him except his heart!
– Currently wearing a LiveVest defib vest until they determine if he needs a permanent one.
Are there any studies – that you know of – that measure the effect of dietary cholesterol on blood cholesterol?
If the body produces cholesterol naturally why do we need to eat any extra?
Are there any studies which show that saturated fat is a dietary necessity?
To answer your 3 questions:
There are lots of studies, Charles. Just search for that topic on the internet: “effect of dietary cholesterol on serum cholesterol”
We can’t avoid eating cholesterol. It’s part an animal’s physiology. Thus it is in our diet because the animals we eat needed it in their bodies.
Also, physiology textbooks will tell you that saturated fat is a necessity. Read online about “lipid bilayer” – the membrane that surrounds all living cells, and most viruses. Saturated fats provide the strength and tension needed for cell integrity. Unsaturated fats provide the permeability needed to exchange waste for new food and oxygen. As far as cell walls are concerned, it’s mostly just fats and cholesterol.
One other question – what is the recommended LDL – P particle number? thanks!
Hi! I’ve just discovered this site, so haven’t done a lot of research, but wonder if Chris, or anyone, can tell me about VLDL. Mine measured 82, and my doctor is flipping out. My total cholesterol is 370, HDL 95, I eat really healthy, non-carb foods. Thank you! Really, thank you!
Chris, I would love to read an article by you (you’re able to make things so clear) discussing particle number vs. particle size. There are some who disagree that is it simply a matter of particle number and that the particle size is the real determining factor although I know that the most current theory is what you have presented regarding particle number. I also tend to wonder if it is really just a concentration gradient issue or what other factors make the endothelium more vulnerable to infiltration in some patients and how big a role those factors play in the process. Thanks for the great articles. You take some of the most complex subjects and make them accessible to everyone. That is a real gift..
The biggest myth that I ABHOR is that eating cholesterol will make you get high cholesterol. OMFG I want to murder people when they say, “oh no, I cannot eat eggs or shrimp because I have high cholesterol” – GAHHHH!! And then, instead, they start noshing on some trans fatty acid laden food… AWESOME. Way to be educated.
In your podcast with Chris Masterjohn a couple years ago he stated “The epic Norfolk study measured by NMR, they found that particle size was useful but they found that particle number was much more useful. But when they adjusted particle number for HDL cholesterol and triglycerides once again its usefulness was very questionable.”
I believe Chirs’s thoughts then were that particle size, number and TC/HDL were all markers for LDL receptor activity and that low LDL receptor activity played a big part in heart disease. At that time he felt that TC/HDL was just as good of marker as particle size/number so if you were unable to get a particle size/number test done then TC/HDL would be a good marker.
Have there been studies published in the last 2 years that show particle number keeps its predictive value when adjusted for HDL, TG or TC/HDL?
As well have there been any studies of the particle number of people with heart attacks. ie do people with very low particle number ever have heart attacks or are almost all heart attacks in people with high particle number?
Glen,
Here is a slide based on a 2002 study, which graphically displays how LDL-P varies both with HDL and TAGs. It also shows where the concordance of LDL-P with LDL breaks down (becomes discordant) with high TAGs and low HDL.
http://www.lipidsonline.org/slides/slide01.cfm?q=framingham+offspring+study&dpg=1
This slide shows joint risk of CAD as function both of HDL and LDL
http://www.lipidsonline.org/slides/slide01.cfm?q=framingham+heart+study&dpg=5
The lowest risk is at HDL>85 and LDL of 100.
This study:” Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines”
http://www.ahjonline.com/article/S0002-8703%2808%2900717-5/fulltext#app1
contains these histograms of LDL, HDL and TAGs.
http://www.ahjonline.com/article/S0002-8703%2808%2900717-5/journalimage?allhighres=false&free=yes&ishighres=false&loc=gr1&src=fig
While admissions with HDL>=80 are about 1% and the admissions with TAGs <= 60 are about 13%, it is unfortunate that there is no analysis provided comparable to the "joint risk" above.
I am very fascinated by these cholesterol articles. I have very high genetic cholesterol. I am 38, in very good physical shape and have been a vegetarian ( to lower my cholesterol for 23 years.) after the birth of my 3rd child, I was diagnosed w Hashimoto’s disease. I refuse to take a statin for cholesterol (it’s in low 300’s range) as I am already taking Synthroid and have adopted a completly gluten free diet for the past year. I am wondering if the Paleo diet would be good for me or only serve the auto immune issue, but make the cholesterol issue worse. Thoughts?
What will make the cholesterol worse is the Synthroid. If you switch to NDT (like Armour), your cholesterol will reduce considerably. The thyroid produces more than just T4, and Synthroid is a T4 only med, which gives many people high cholesterol and sometimes even heart failure.
Your thyroid’s active form is T3, one way you can activate your thyroid from T4 to T3, is eat some unproceesed carbs, and lower fat intake a little bit (you still need fat (especially saturates) since vitamin A actually keeps a functioning thyroid). Also, just a little bit, replace a little SFA with MUFAs and eat less fatty cuts of ruminant meat just for a bit. And eat lots of food containing iodine, selenium and iron with fat soluble vitamins A, D3 and K2 so fish and shellfish, liver and egg yolks, some butter and cheese and some unprocessed starchy carbs to fix your thyroid. Seecondly, don’t worry about LDL levels, be more concerned about its particle number. SFA makes LDL particle size bigger and denser while excess carbs make LDL particle size smallr and fluffy which is problematic.
I guess after reading all of this, is there ever a “good” time for someone to go on statins? My dear friend switched to paleo, and while every other marker in his life improved, his cholesterol didn’t at all. In fact, it is really high. He went to two or three different doctors to make sure, but finally submitted to the last doctor (supposedly the best cholesterol doc in Chicago) and took the statin prescription.
thanks,
Shane
Hi chris
Thanks for the article. Just curios if lipo protein b or a is a reliable measurement as they don’t test particle size in Australia
Michael, in Australia ApoB is the closest you’ll get to an LDL-P reading. Every LDL particle has one ApoB attached so it’s a fairly close proxy.
A paleo-based diet results in low serum triglyceride and high total cholesterol levels. The three most important factors of cholesterol testing:
1) The ratio of triglycerides to HDL-cholesterol is what shows strongest association with the extent of coronary disease.
– http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664115/
2) Having triglycerides under 100 is correlated with Pattern A LDL particle size (the healthier pattern), which also often lead to high measured LDL.
– http://www.ncbi.nlm.nih.gov/pubmed/1420088
3) “In patients with low serum triglyceride and undesirably high total cholesterol levels, Friedewald equation may overestimate LDL”
http://www.ncbi.nlm.nih.gov/pubmed/18426324
Friedewald equation:
Total – (HDL + [Trigs/5]) = LDL
There is a newer equation, called the Iranian Equation, that does a better job of calculating LDL when trigs are below 100. That equation is:
(Total/1.19) + (Trig/1.9) – (HDL/1.1) -38 = LDL
Zingiber,
Without you explicitly stating it, the articles and equations you mention are saying to me:
LDL is computed after measurement of Triglycerides, and analysts don’t trust the LDL to be accurate and also it seems to be higher in patients eating a healthier diet. We are all saying “What gives?”
It’s possible that by looking at LDL the big-Pharma community has everyone looking the wrong way again? Several readers here have already stated: “Why measure LDL?”.
It seems to be coming out of all these tests of diet on cardiovascular problems that there are 2 things that really should be focused on, and yet big-Pharma has us looking at LDL.
The two things are:
1) Triglycerides – you elevate your triglycerides by eating high carb meals. There is no leeway for allowing elevated glucose in the blood. Eat carbs and you body must store them immediately, as soon as the glucose hits the blood. When the liver is full and the muscles are full (most people on poor diets have their gauges at “full” all the time) then the liver changes the glucose to triglycerides to be transported to storage in your fat cells.
2) Oxidized polyunsatured fats in the diet – This gets measured as “oxidized LDL”. I believe this just means LDL that happens to be transporting an oxidized fat, which in the SAD is most likely going to be over-heated vegetable oil or else a trans-fat. The lipoprotein itself cannot be oxidized. It is the fat that it is carrying that is oxidized.
So some of the recent tests seem to show that low triglycerides is good, and that just counting LDL doesn’t prove anything because there is proof that LDL can rise (and WILL rise when you lower triglycerides) and the people are actually less likely to have heart attacks. Other tests show it is the oxidized LDL (which isn’t really the number, size or anything to do with LDL [the vehicle, remember?] but just the passenger being carried [read “transfat”] that is causing the scarring of the endothelium, and thus the atherosclerosis that leads to heart attacks.
Here’s the kicker. What we are seeing is a “correlations” in a lipid panel and the scientific community has us busy trying to fix our systems by lowering just one number (LDL). This probably is bogus. We are thinking the correlations are due to a 1-factor CAUSE-EFFECT relationship and are trying to bring people to health by adjusting diet to change the one measurement.
The real “correlation” between triglycerides and LDL and a poor cardiovascular system is based on 2 things in the diet (at least), and is characteristic of the typical SAD diet: eating too many carbs, and eating too much ruined fats. Time and time again, when people are tested on healthy diets (as in organic, paleo) vs SAD, the LDL numbers can rise, yet the people are far less likely to have heart disease.
As I cited before; http://www.jpands.org/vol10no3/colpo.pdf
As many have pointed out here, with LDL being a computed number, all it takes is a change in triglycerides to get a change in LDL. The quickest way to drop triglycerides is to go very low on carbs. The change can be measured within a day. The result in a test will show an elevation in LDL. Big deal. So much for those measurements.
In a test, they can feed any food they want. They could go low-carb and still have the people eating junk-food type fats.
But in real life, when people are astute enough to be trying a ketogenic or just a relatively low-carb diet, they are usually also eating more green veggies (vitamins, enzymes, anti-oxidants! yum!) and they are eating mostly healthy fats, and have laid off the cheap veggie oils, fried foods, etc. that would result in “oxidized LDL”. So what you get in this situation is what looks like a “correlation” of certain lipid measurements with heart health, but is in reality measuring a correlation of two things (carbs and ruined fats) that were changed in the diet simultaneously, and resulted in a healthier body. As the cited paper points out, heart health depends more on several things, than one thing, and the most important thing may be the amount of anti-oxidants one eats (meager supply in the SAD) and not the type of fats one eats. Read the study.
Now here is more on how trans fats cause the endothelial scarring and calcium deposits:
http://www.sciencedirect.com/science/article/pii/S1567568806000328
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029600
http://ajcn.nutrition.org/content/70/5/832.long
These studies are showing a correlation between trans fats and atherosclerosis. But there are others that have indicated that any kind of ruined polyunsatured fats in the blood stream also do damage.
My conclusion (not recommending necessarily to others) is to forget about getting my blood checked, and just change my diet to one that is nutrient dense on micronutrients (green leafy veggies), and is essentially low-carb. That means very healthy organic fresh foods, including all meats, and other sources of oils. It means low-heat cooking.
I had a stent put in my LAD after unstable chest pain getting worse and culminating in 3 almost heart attacks. This was followed by coronary artery bypass graft age 54: normal cholesterol numbers, low blood pressure, healthy SAD. All of my docs said it was a ” plumbing problem” and put me on a statin, blood pressure meds and a blood thinner. This was in 2005, and i read everything i could get my hands on, ending up sending my blood on my own for the NMR lipoprofile. LPL particle size almost 2000! None of my docs saw the significance of this. I put myself on plain flushing niacin, starting out at 50 twice a day, and ended up at 1000 mg x2. ( better to not take more than twice due to elevated liver enzymes). My LDL – P went down to 600. I have been paleo since 2011 and went off niacin to see what would happen, and it shot back up to 1800!
Statins don’t touch ldl- p, but at one point my cholesterol was around 100 total and i felt very wierd. Long story short, off all heart meds, and HDL was 100 last blood test, Tg was 63 and LDL was 122.
If you decide to take niacin be careful with the sustained release it can cause problems.
How long did it take to change your LDL p with the niacin?
I have always thought that it is inflammation that causes heart disease and cholesterol just patches up the inflamed areas in arteries. This is what I have read everywhere so far. I am confused now.
I think you are right, Alina. Don’t be confused. Here’s more on that. I used these links elsewhere in a comment, but they pertain to your thoughts as well:
http://www.sciencedirect.com/science/article/pii/S1567568806000328
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029600
http://ajcn.nutrition.org/content/70/5/832.long
These studies are showing a correlation between trans fats and then inflammation and resulting atherosclerosis.
Chris,
What are your thoughts on phytosterols on atherosclerosis? Peter Attia mentions this as having a stronger connection than even oxLDL does and in the vein that industrial seed oils have been categorized as “Heart healthy” because they reduce cholesterol… And of course is not the idea ( we are hoping for).
He also mentions corn as having the highest amount of phytosterols. I’m very interested in the biggest contributors to a westernized Mexican diet to CVD and the least problematic/healthy diet options.
Henry
Chris,
Thanks for the great article and research. My question is this- what test should I specifically request from my MD in order to obtain my LDL particle number?
Thanks!