The Science Behind Reversing Heart Disease

Updated: Mar 11, 2020

A scientific analysis of the most important pillars of the diet that has proven most successful in reversing heart disease, and a look into why the general guidelines differ from this protocol.

What are the main pillars of Dr. Esselstyn's heart reversal intervention?

  1. A Low Fat Whole Food Plant Based diet

  2. An emphasis on the Endothelium

  3. An emphasis on Nitric Oxide

  4. Getting your Total Cholesterol (TC) Under 150 mg/dL or about 3.8 mmol/L and getting your LDL Cholesterol Down to at least 80 mg/dL or about 2 mmol/L

1. Low Fat Whole Food Plant-Based Diet

We discussed and analyzed the diet in "How to Reverse Heart Disease with Diet"

If you haven't read it yet or if you want to refresh your memory, check it out.

2. Endothelium

Improving the endothelium or endothelial function is probably one of the most emphasized facets of Dr. Esselstyn's plan. Even if one would not follow Dr. Esselstyn's plan completely, knowing and applying the information in regard to improving this delicate and vitally life generating organ system, would probably be one of the most important steps you could undertake.

The endothelium, a highly dynamic cell layer, covers the entire vascular system that is full of with life and every bit as active as any other organ in the body. It can even regulate the development of other organs. How impressive is that? (1)

In adults, approximately ten trillion cells form an almost 1 kg `organ'! (2)

The endothelium is involved in a multitude of massively important physiologic functions:

  • It controls the dilation and constriction, or widening and narrowing, of the arteries and other blood vessels.

  • It maintains blood fluidity and circulatory function.

  • It transports cells and nutrients.

  • It supports the growth of new blood vessels.

  • It maintains the walls of the blood vessels. (1)

These functions aren't just vitally important for people with cardiovascular disease.

If any of these functions are compromised, health is compromised as a result.

In "Reversing Heart Disease" we have showed what devastating the effects atherosclerosis can have on your arteries which is visible on this Angiogram on the left (A).

But even if there is no visible damage on the angiogram, any sign of endothelial dysfunction provides a clear warning sign of the development of future cardiovascular events, such as heart attacks. (3)

Lowering cholesterol, more specifically LDL, (discussed further down the line) is not only important to minimize the buildup of fatty streaks within the arteries (atherosclerosis), but also to protect the endothelium from being impaired and fulfill its normal functions, due to the reduction of nitric oxide. (4), (5)

3. Nitric Oxide

Nitric oxide is absolutely essential to vascular health — a finding that won the Nobel Prize for Medicine in 1998. (6)

Endothelial nitric oxide protects against atherosclerosis and the buildup of plaque. Any atherosclerosis present reduces this protective gaseous compound from fulfilling its duty. (7)

When nitric oxide is reduced, it leads to endothelial dysfunction, which sets you up for vascular damage and future coronary events, such as a heart attack or stroke. (2)

4. Cholesterol Levels

Cholesterol is a substance your body can produce on its own, but it can be raised as a result of the food you eat. For convenience we usually speak about 'good cholesterol' or High Density Lipoprotein (HDL) and 'bad cholesterol' or Low Density Lipoprotein (LDL).

Technically, neither HDL nor LDL is actual cholesterol. They are merely the vehicles that carry cholesterol around.

It's just that if there are a lot of LDL vehicles, they are more likely to dump the cholesterol in your arteries, whereas the HDL vehicles take the cholesterol from other parts of the body back to home base, the liver. (8)

This section below mentions a lot of numbers.

If you hated math in school, then this probably doesn't sound too good right now.


...don't worry!

The values and numbers themselves are not necessary to understand on their own.

To form a conclusion about the whole cholesterol story, we DO need them to give us direction though. Let's hope that sounds convincing enough for you to keep reading.

Dr. Esselstyn advises to get your total cholesterol (TC) under at least 150 mg/dl or 3.88 mmol/L. How does that compare to the federal guideline set by The American Heart Association (AHA)?

The AHA states a TC of about 150 mg/dL is ideal. They sort of seem to be on one line here, although Esselstyn sees it as a limit and not as something ideal.

A note to make here is that Dr. Esselstyn made this recommendation DECADES before the The American Heart Association (AHA), which lowered their recommendation to 150 only recently, which is quite astonishing.

(9), (10)

How about Low Density Lipoprotein (LDL)?

Dr. Esselstyn prefers you to go below 80 mg/dL or about 2 mmol/L.

What about the The American Heart Association (AHA)?

They state there is no ideal target level, but in the same sentence they say that the lower is better and aim for a 100 mg/dL or lower (<2.6 mmol/L). (10)

The difference seems more substantial here.

Dr. Esselstyn likely based his numbers on evidence where an LDL below 80 arrests the progression of atherosclerosis (11) and improves inflammation and endothelial dysfunction, both important markers of abnormal vascular health. (12)

We have plenty of science nowadays, that shows that if your LDL is low enough, mortality decreases significantly.

So what are these magic numbers and how do they compare to the ones above?

For that, we have to look at some graphs below.

If you, besides math, also really hated statistics, then I offer you my sincere apologies and hope you will recover soon from the onslaught of data 🤯.

The graphs are actually fairly easy to understand.

The lines in the graphs going up, means the LDL is going up as you can see on the horizontal lines or horizontal axis (x-axis). It also means heart disease risk rises as you can see on the vertical lines on the left we call the vertical axis (y-axis).

The lower the line goes the lower the LDL and the lower the risk of heart disease.

In one study, where they measured the amount of plaque inside the arteries (atherosclerosis), you can see the lower the LDL goes, the lower the rate of atherosclerosis (see graph below). When it drops down to 50-60 mg/dL or 1.3-1.55 mmol/L, there are

no signs of atherosclerosis at all, which you can see from the red columns. (13)

In two other studies (see graphs below) they suggests that an LDL cholesterol value 67- 75 mg/dL or 1.7-1.9 mmol/L stops the progression of atherosclerosis. (12), (14)

To prevent a heart attack from happening, lower than that is even safer as the number of coronary events on the left (CHD events) goes down: (12)

And if you've had a heart attack before, then lower is even better: (12)

As you can see, lower cholesterol, more specifically lower LDL clearly lowers risk of cardiovascular disease. (12), (13), (14)

That's perfectly in line with people, who have genetically low cholesterol where the rates of heart disease are significantly lower in comparison to other populations and actually live longer on average. (12), (15)

If we look at the data we have on native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis) the physiologically normal range seems to be 50-70 mg/dl or 1.3-1.8 mmol/l. (12)

As we can see from the tables and graphs presented above, atherosclerosis is virtually non-existent in this range. Perhaps not surprising, that the LDL of newborn infants falls exactly within this range as well. (16)

Dr. Esselstyn may seem like quite the meany when it comes to diet, but he actually is rather friendly when it comes to getting your LDL down, where he sets the limit at 80 mg/L (2 mmol/L).

Granted, he sets it as a limit. He does think lower is better.

WHY is the general consensus different?

Why is this kind of diet not generally recommended if it has proven to work substantially better than anything else?

That is a complex, yet very relevant question.

First of all, there has been confusion regarding what constitutes a “normal” blood cholesterol level for a long time. (17) Even today, looking at the guidelines, they aren't too confident about it:

While there is no ideal target blood level for LDL-Cholesterol, the 2018 guideline recognizes, in principle, that “lower is better.” (10)

The average cholesterol in many nations across the globe, both total and LDL, is actually unhealthily high. (18) Not exactly surprising, since our number 1 cause of death is heart disease.

How come there is this confusion then?

As you've just learned there are multiple lines of evidence that show that higher levels of cholesterol in the blood (specifically LDL) increase the chance of dying from heart disease.

Scientist Daniel Steinberg noted:

"By 1970, many leaders in atherosclerosis research were firmly convinced that cholesterol lowering would work (well before the introduction of statins (cholesterol lowering medication). However, dietary intervention had only limited effectiveness and compliance was not easy to effect."
"There was an unwillingness to accept the notion that a very large fraction of our population actually has an unhealthily high cholesterol." (17)

Dietary interventions were limited that time, so that explains their lack of effectiveness.

What further stands out is:

"There was an unwillingness to accept the notion that a very large fraction of our population actually has an unhealthily high cholesterol."

Why this unwillingness?

And how has that developed over time?

The National Institutes of Health's Cholesterol Education Program (CEP) reported already many years ago, in 2002, that the reason the government doesn’t recommend everyone to shoot for an LDL of even just under 100 mg/dL (2.6 mmol/L), is that despite the lower risk accompanying more optimal cholesterol levels, the intensity of clinical intervention required to achieve such levels for everyone in the population would financially overload the health care system. Drug usage would rise enormously. (19), (20)

They think drug usage would rise, because their concern is that people generally would require an LDL-lowering drug, like statins, to achieve a low enough LDL cholesterol of even a 100 or lower.

I guess that they hadn't heard that a physiologically normal LDL is approximately 50-70 mg/dl. We didn't evolve with the help of statins.

We've seen what the American College of Cardiology (ACC) and the American Heart Association (AHA) recommend, namely an LDL of 100 or lower, but among children, <110 mg/dl (2.8 mmol/L), is acceptable.

What about the European Society of Cardiology (ESC)?

ESC recommends an LDL below 116 mg/dl (3 mmol/L) among low risk populations.

Higher risk populations should lower LDL further to below 70 mg/dl.

They further agree that the lower the LDL, the better and that higher risk populations should lower their LDL more substantially. (10), (21), (22)

The ACC and AHA apparently have changed their minds over the years, because now an LDL of a 100 mg/dL is more feasible. However, these levels are still not completely safe as you've come to understand.

Atherosclerosis is not uncommon even in those with relatively “normal” LDL levels (90 to 130 mg/dl. Moreover, the 10% of the population with the highest LDL levels account for only 20% of the Coronary Heart Disease (CHD) events, like heart attacks. Thus, focusing treatment only on those with very high cholesterol levels will ignore all the other people destined to suffer a Coronary Heart Disease (CHD) event. (12)

This information comes from a study before they updated the cholesterol guidelines. Since then 'ideal' Cholesterol and LDL numbers were lowered.

That means, that these numbers will not be as accurate anymore. HOWEVER, the point the study makes still remains valid, because people regarded to be at low risk, will actually still be at an increased risk due to their LDL being outside of the 'safe zone' as discussed earlier.

As you can see, these cholesterol guidelines fall dramatically short. Only high risk populations will actually fall in a more physiologically normal range. A range where atherosclerosis progressions can be halted.

Although guidelines have improved over the last decade, this approach still ignores a large part of the population with atherosclerosis.

The fact that children are allowed to have higher levels according to the AHA/ACC, is slightly mind-boggling, since it is well recognized that atherosclerosis and the development of fatty streaks start in childhood. (23), (24)

Although guidelines have come more in line with the science and Dr. Esselstyn's views, it seems that there is still some unwillingness to accept, that a large part of the population is at risk.

Esselstyn stated that the reason given by the federal government for not advocating what the science shows is best was that it might frustrate the public. (25)

"Rather than set a truly safe level of blood cholesterol and advise Americans how they can achieve it, the experts balk— often explaining that the public might have an overwhelming sense of frustration at not being able to comply with the nutrition changes necessary"

In the medical profession, people not adhering or complying is a common phenomenon, so it's not surprising. (26)

In my personal experience, I have heard a member of a nutrition center, in charge of communicating nutritional guidelines to the public, make a statement about adherence once.

The recommended amount of vegetables provided in the guideline was actually less than optimal, because of the belief the organisation had, that the people couldn't adhere to it or that it would make them frustrated and lose motivation.

Basically, part of why recommendations are not ideal is because they think you are not capable of reaching that goal. This condescending approach is not in favor of the public or general health.

It's up to the public, YOU, to decide whether or not you follow guidelines or protocols.

You need to have freedom of choice. Whatever you decide to do is up to you, but at least you have a choice. You deserve to know what is the healthiest.

Besides this, don't think that all medical professionals and scientists fall within optimal range.

We know from big cohort studies that followed health professionals and nurses overtime, that they weren't much different. (27), (28), (29), (30)

If medical professionals can't get within range, then this can only strengthen a sense of denial towards optimum health.

Food Lobbies

What else can affect nutritional guidelines?

Nutritional guidelines can be corrupted by food industries.

If you place an insurmountable amount of trust in your government to have your best interest at heart, then this may sound like a conspiracy theory. But unfortunately, it is most definitely not.

Christopher Gardner, a nutrition scientist at Stanford, says:

"A lot of the advisory committee's recommendations didn't make it into the guidelines, and the health professional community is disappointed...."

He adds:

"We realize that dietary guidelines are hugely political issues..." (31)

Walter Willett, former chair (of 25 years) of the Department of Nutrition at Harvard Chan Public School of Health, said, in respect to food industry influence:

“The current system opens the guidelines up to lobbying and manipulation of data,” (32)

It's not just the United States.

In general, when it comes to nutrition policies, large multinational companies frequently have a great influence because of their economic power, government lobbying, and communication and marketing resources.

Unclear laws on conflicts of interest can further increase industry influence. (33)

That means that lobbying strategies from food industries can greatly affect health policy decisions.

But just use common sense here.

Go to your average supermarket and look at what's available. Ask yourself: How many of the products a supermarket sells is heavily refined?

How much of the 'affordable' food is actually good for you?

How much of the junk food is 'very affordable'?

As research scientists have put it:

"Governments should promote the food industry’s shift towards healthier foods, taking advantage of rapidly rising consumer demand.
Incentives should promote research, development and marketing of healthier foods in the food industry.
They should create a food environment wherein healthy foods are accessible, affordable, and desirable.
Disincentives for marketing and promoting, for example, sugar sweetened beverages and junk foods or removal of industry tax benefits for development and marketing of unhealthy products." (33)

Notice the last part, "removal of industry tax benefits".

What does that mean?

That means governments subsidize or create financial beneficial situations for companies to sell the junk food you as a consumer buy.

Governments can therefore not have your best interest at hand. At least not in regard to your health.

In addition, there is plenty of evidence that the right use of taxes and subsidies can improve the health of the public. (34), (35), (36), (37)

A final summary

If you have any degree of atherosclerosis, it means you need to change whatever you are doing, if you want to reverse that. Especially if you've already had a coronary event, such as a heart attack.

There's absolutely no doubt that you have the power to improve the quality of your own life, regardless of the risk factors you carry with you.

There is plenty of science to support Esselstyn's theories, but in the end, it's all about real world results. Even though Dr. Esselstyn's approach is considered by many as a drastic approach, it is an approach that has proven itself more than any other approach.

The importance of nitric oxide and a healthy endothelium are important pillars of the intervention. In combination with a focus on lowering your 'LDL cholesterol' and a low-fat, whole food plant based diet, you can become 'heart attack proof' as Dr. Esselstyn often states.


  • By consuming foods that promote the production of nitric oxide allowing the endothelium, the delicate inner lining of your arteries, to function at its best.

  • By avoiding foods that harm the endothelium, no matter how little that harm may be.

Can you incorporate only certain parts of the diet?

Of course you can. It's entirely up to you what decision you make.

As far as results go, the more you can incorporate the more protected you are likely to be.

Incorporating some part of the diet is surely better than incorporating nothing at all.

Lastly, federal guidelines, although not terrible, aren't the most reliable or ideal as you've come to understand. They are, however, infinitely better than the average western diet.

With this, part 3 in the series of reversing heart disease ends.


Whenever your situation looks bleak, never lose heart.

Take heart in the fact that, if you set your heart on finding a way and follow your heart, it will surely do your heart good💓💗







































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