The Cholesterol Myth and what President Eisenhower’s case teaches us

President Dwight D. Eisenhower suffered his first heart attack at the age of 64 in Denver Colorado, September 1955. During his 6 weeks stay in the hospital, his physicians gave press conferences twice daily and started to educate Americans about the risks of heart disease. By the time Eisenhower’s health returned, Americans had learned to watch their cholesterol and fat in their diets. Eisenhower himself has learned the same less even though with questionable results.

At the time of his first heart attack, his cholesterol levels were below average at 165mg/dL, he was at a normal weight and had no history of heart diseases. He used to be a chain smoker but stopped a couple years ago.
After his heart attack, President Eisenhower changed his way of eating towards a low fat and extremely low cholesterol diet. His meals were prepared in plant oils or margarine instead of butter and he reduced his egg and red meat consumption to a minimum.

However, his cholesterol, which has been low and stable before, suddenly started to rise. By 1960, his cholesterol reached 223 mg/dL, which kept increasing to above 250mg/dL, levels that most physicians consider as a high risk for heart diseases.

One year later, Ancel Keys made it on the Time magazine, promoting his hypothesis of a low cholesterol diet to prevent heart diseases and the American Heart Association went along and announced the official endorsement of low cholesterol and low fat diets as means to prevent heart diseases.

 
Ancel keys and cholesterol.png
 

Eight years later, Eisenhower died of heart failure, age 78. By then he had another dozen heart attacks. President Eisenhower’s case could have taught us at least one lesson, if we would have paid attention.

The lesson is that dietary cholesterol has little to do with our blood cholesterol and even less with heart diseases.

Dietary Cholesterol and Blood Cholesterol

A meta-analysis published in 2015 looked at 17 trials using dietary interventions as a way to study the effect of ingested cholesterol on blood cholesterol levels. [1]
Most trials compared diets in which the cholesterol intake was around 800mg/day, which is almost three times the amount of the daily recommendation, to a low cholesterol diet of 200mg/day. Not entirely surprisingly, there was an increase in the groups on the high cholesterol diets. But despite the 4 times higher intake of cholesterol, the average increase on blood cholesterol levels were meager 11.2mg/dL.

The body tightly regulates the amount of cholesterol in the blood by controlling its production and uptake. When your dietary intake of cholesterol goes down, your body simply produces more or increases the uptake and vice versa. [2]

Cholesterol is essential for life as it is a major component of each of our cells, it contributes to the membrane structure and is further needed to make hormones like testosterone and vitamins like vitamin D.

Cholesterol synthesis and uptake.jpg

The meta-analysis also looked at forty studies that examined the risk of high dietary cholesterol on heart diseases but found that: “Dietary cholesterol was not statistically significantly associated with any coronary artery disease or ischemic stroke.”

Dr. Jonny Boweden, author of the book The Great Cholesterol Myth explains that: “More than 50% of the admissions to hospitals in the USA for cardiovascular diseases happen to people with normal cholesterol and at least 50% of people with elevated cholesterol have very normal healthy hearts.” [3]

“Good” Cholesterol vs. “Bad” Cholesterol

Unlike at the times of Eisenhower, we now know that there are many different kinds of cholesterol. Commonly known are the “good” HDL and the supposedly “bad” LDL. In fact, there are at least five different types of cholesterol that describe the way cholesterol is packed and transported, as cholesterol is never really in our blood but packed in so-called lipoproteins.

classification-of-lipoproteins.gif

All of them carry a different composition of lipids and fulfill different tasks. LDL cholesterol is generally viewed as the risk factor for heart diseases. However, this view might be wrong, as well. A study published in the American Heart Journal looked at more than 130,000 people that were hospitalized with coronary artery diseases but found no correlation between elevated LDL cholesterol and heart diseases. They conclude their findings by saying that: "patients hospitalized with CAD, almost half have admission LDL levels <100 mg/dL", which is considered as low LDL levels. [4]

Image from reference [2]

Image from reference [2]

Why did we start looking at Cholesterol?

A police officer sees a drunk man crawling on hands and knees under a streetlight. When the officer ask the drunk what is he doing, the drunk says that he is looking for his keys.
“Is this were you lost them?” The officer ask.
“I don’t know, the drunk says, but this is where the light is”.

This phenomenon is known as the streetlight effect and describes a type of observational bias. For the 60 years, cholesterol was where the light was. Much of it started with Ancel Keys 7-Country Study [5] and the fact that physician were able to measure total cholesterol before many other more relevant factors. The history of it would be a whole blog by itself.

What causes Heart Diseases?

As we have seen, the total cholesterol levels are basically meaningless as they combine so many different types of cholesterol. The only one factor, which is probably worth watching, is your triglyceride levels.
Liver triglycerides are packaged into very low-density lipoproteins, or VLDLs, which are then exported into the blood.
Elevated VLDL cholesterol levels were found to increase Coronary Heart Diseases risk by 2.0 to 3.0 fold. [6] [7]

TG framingham study.gif

There are ways to reduce triglyceride levels. A trial published in 2007, divided people into four different carbohydrate-restrictive diet groups, ranging from a low-fat to a low-carb diet. The low-carb diet showed the greatest reduction in triglyceride levels (-52.3mg/dL after 2 months) compared to the low-fat diet (-10.9 mg/dL). [8

Especially added sugar consumption not just increases triglyceride levels but seems to be directly associated with heart diseases. A study found that people who consumed at least 25% of calories from added sugar were twice as likely to die from heart disease as those who consumed less than 10% of calories from added sugar. [9, 10]

Another risk factor for heart diseases is chronic inflammation. Having slightly elevated C-Reactive Protein levels (a marker for inflammation in the body) puts you at a much higher risk of heart failure. [11]

We find cholesterol in plaques because it acts like a fireman. It acts like a bandage for arteries that are damaged. “Blaming Cholesterol for heart diseases is like blaming the fireman for causing the fire only because he happens to be at every single fire”

We find cholesterol in plaques because it acts like a fireman. Immune cells trying to repair a wound in an artery require cholesterol but if the inflammation can't be resolved they become "exhausted" and show an uncontrollable uptake of cholesterol and a defect in its release.

“Blaming Cholesterol for heart diseases is like blaming the fireman for causing the fire only because he happens to be at every single fire”

Take Home Messages:
- There is no association between dietary cholesterol and heart diseases.
- Total blood cholesterol is insignificant for heart diseases.
- Elevated triglyceride levels are associated with heart diseases and are increased by intake of carbhohydrates and sugar.
- Inflammation is at the root of heart diseases.

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References

  1. Berger et al., Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis., Am J Clin Nutr. 2015

  2. AHS12 Peter Attia, MD — The Straight Dope on Cholesterol, Slide 8, https://www.youtube.com/watch?v=8GDx5sObceI&t=1672s

  3. Dr. Jonny Bowden "The Great Cholesterol Myth", https://www.youtube.com/watch?v=YGOpjPNtjes&t=2694s

  4. Sachdeva et al., Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines, American Heart Journal, 2009

  5. https://en.wikipedia.org/wiki/Seven_Countries_Study

  6. Castelli, Epidemiology of triglycerides: a view from Framingham. Am J Cariol, 1992

  7. Ren et al., Long-term coronary heart disease risk associated with very-low-density lipoprotein cholesterol in Chinese: the results of a 15-Year Chinese Multi-Provincial Cohort Study (CMCS)., Atherosclerosis, 2010)

  8. Garner et al., Comparison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women, JAMA, 2007

  9. Stanhope et a., Consumption of Fructose and High Fructose Corn Syrup Increase Postprandial Triglycerides, LDL-Cholesterol, and Apolipoprotein-B in Young Men and Women, JCEM, 2001

  10. Yang et al., Added sugar intake and cardiovascular diseases mortality among US adults., JAMA Intern Med.

  11. Kardys et al., C-reactive protein and risk of heart failure. The Rotterdam Study, American Heart Journal 2006