Dietary Cholesterol: Does it Matter?

While staying a couple of days in the hospital for the birth of my daughter, I received 3 free meals a day, which I was very happy about! The menu was also well laid out and patient friendly. I noticed that they had "healthy" options, meals for cardiac patients, and food for patients on liquid diets like my pregnant wife. My eye was drawn to a section of the menu about cholesterol in which meals that were low and high in cholesterol were called out using symbols. Seeing these brought me back to pharmacy school when we learned about the DASH diet and other ways of eating that could decrease your cardiac risk. One such way was to limit how much cholesterol you consumed. We were taught that patients with risk factors for heart disease shouldn't eat more than 200 mg/day.

I remember raising my hand and asking the professor why this mattered. Wasn't it the case that dietary cholesterol had little to no effect on circulating cholesterol levels? Having not received a totally convincing answer, I walked away from that class like most students and memorized the 200 mg number, which many would regurgitate to patients later. That was until I started writing about the number one killer of Americans in the 21st century and the thought came back to me... Does dietary cholesterol really matter?

The vast majority of the data for this week's article comes from a publication in Circulation by the American Heart Association (AHA) in 2020. In that publication, Carson JAS et al. provided a scientific advisory for dietary cholesterol and cardiovascular risk, along with a great history of recommendations for cholesterol consumption in the United States. Speaking of which, the 200 mg number I mentioned earlier was pulled from the National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia in 2015, which was taught to me in 2018 as a pharmacy student. Specifically, the guidance was as follows: "A diet that has a total fat content of 25–30% of calories, saturated fat content of ≤7% of calories and dietary cholesterol <200 mg/day is beneficial in lowering LDL-C and non-HDL-C." Note: LDL-C and HDL-C stand for low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, respectively.

So, what are the current recommendations from the major players in this space? Turns out that the AHA, American College of Cardiology (ACC), and Dietary Guidelines for Americans (DGA) have all removed recommendations for specific daily cholesterol intake. There are a ton of reasons for this, and we will talk about some of them here. However, for a comprehensive understanding, I would suggest reading the entire article from the AHA.

Let's start with the typical cholesterol intake in the United States which was 293 mg/day in 2014. This means that the average American was already consuming the recommended amount of daily cholesterol for healthy adults, which the US Department of Agriculture determined to be <300 mg/day at the time. Remember that the 200 mg cutoff was for patients with dyslipidemia. Because of this, many of the studies looking at the effect of dietary cholesterol on cardiovascular health will use a cutoff of <300 mg/day as a control.

But what do all of these studies say? The honest answer is that the data is all over the place. This is often the case in nutritional epidemiology. But generally speaking, neither findings from observational studies nor interventional studies have supported an association between dietary cholesterol and cardiovascular disease (CVD) risk. This is also the case for egg consumption! Eggs are the source of roughly 25% of all dietary cholesterol in the United States. For reference, one large egg contains ≈186 mg of cholesterol. That's nearly ALL of the cholesterol a patient with dyslipidemia would have been recommended to eat in 2015.

To reiterate, the data is not at all consistent. Dietary cholesterol or egg consumption was associated with all of the following in different studies:

• Stroke
• Protection from stroke
• Heart disease
• Protection from heart disease
• Increased total cholesterol
• No effect on total cholesterol
• Increased LDL-C
• No effect on LDL-C
• Increased HDL-C
• No effect on HDL-C
• NO EFFECT (MOST COMMON OUTCOME ACROSS ALL STUDIES)

For me, these results aren't surprising, especially given the numerous deep dives we've taken on RxTeach into the differences between LDL-P, LDL-C, ApoB, Lp(a), and all of their associations with atherosclerotic cardiovascular disease (ASCVD). For this reason, I tend to agree with the current approach of the ACC, AHA, and DGA in removing the old recommendations for dietary cholesterol. Having said that, I don't agree with some of the other statements in the AHA guidelines like, "For older normocholesterolemic patients, given the nutritional benefits and convenience of eggs, consumption of up to 2 eggs per day is acceptable within the context of a heart-healthy dietary pattern." Am I to believe that 3 eggs per day is unacceptable? What about 2 eggs per day plus 3oz of shrimp (equivalent to a 3rd egg in cholesterol)? If egg consumption wasn't "convenient", would the number be lower? Unless the cholesterol in the eggs is the ONLY cholesterol consumed throughout the day, everyone eating 2 eggs will be moderately over 300 mg/day. Also, total dietary cholesterol would still vary wildly from person to person depending on the rest of their diet outside of eggs. This is the case even when following "a heart-healthy dietary pattern", which they claim includes lean meats like chicken and (apparently) vegetable oil. Then there's the mention of age as this AHA recommendation is for people that are "older". What does that mean? 65 years old, 50 years old, 40 years old? Does the reference data support an association with cholesterol and CVD as we age, or is aging what increases the risk of CVD? Isn't this why when adjusting for age, the positive associations disappear in the listed studies? The only study in the guideline that specifically calls out "older" participants showed no association between dietary cholesterol and CHD (56–65 years old, P=0.364, adjusted for risk factors and energy intake).

It's for reasons like this that I don't agree with putting a number on a specific food group (like eggs) especially considering it makes up a tiny portion of daily calories (≈140 calories for 2 eggs or 7% of a 2,000-calorie diet). Not to mention all of the other nuances like size. Is a 110 lbs. female supposed to eat the same number of eggs as a 220 lbs. male? It just doesn't make sense to me.

Now, I would never say that there's no evidence to support an association between dietary cholesterol and cardiovascular risk, because there are clearly studies with that conclusion. However, I fail to see a case for dietary cholesterol limitation when looking at the data as a whole. In my opinion, the only reason to "limit" cholesterol intake would be to decrease calorie consumption in general, which can be very beneficial. This explains why many of the "positive" studies associating dietary cholesterol with CVD became useless when adjusted for overall calorie consumption. The more calories you eat, the more cholesterol you'll consume and vice versa. Cardiovascular disease is an energy intake problem, not a cholesterol one. The only reason we care about LDL-C is because it happens to be a pretty good proxy for Apo-B. The good news is that eating less cholesterol is also very unlikely to be harmful in any way. This is why I don't believe the previous recommendations caused any damage to patients either.

For all of the healthcare providers out there, you might be asking yourself, "What about ezetimibe?" For the uninitiated, ezetimibe is a medication that was first recommended in the 2018 Guidelines on the Management of Blood Cholesterol specifically for "...patients with clinical ASCVD who are on maximally tolerated statin therapy and are judged to be at very high risk and have an LDL-C level of 70 mg/dL or higher (≥1.8 mmol/L)..." The thing about ezetimibe that makes it interesting is its mechanism of action. To reduce circulating cholesterol, ezetimibe inhibits the absorption of cholesterol by the small intestine. This might suggest that dietary cholesterol must be playing a role, otherwise the clinical data for ezetimibe would have never been positive, right? Wrong. Intestinal cholesterol is derived primarily from cholesterol secreted in the bile which is part of your body's ability to "recycle" cholesterol using the liver and biliary systems. This also happens to be the idea behind bile acid sequestrants, which are hardly used anymore. On the other hand, your dietary cholesterol is barely being absorbed, if at all.

Hopefully you found this article interesting and informative! If anything, I hope you're a little bit less worried about eating eggs. They're not going to kill you (in my opinion). To conclude, I'd like to expressly point out that dietary cholesterol recommendations have changed a lot over the years. This is important to understand. The things you learn in school will often be proven wrong. That's how science works.

I'm reminded of a presentation I heard from a PharmD graduate that went on to get his MD. He was speaking about how pharmacists are often married to guidelines. I find that to be true most of the time, and I certainly felt like a lot of my schooling was focused on memorizing guideline recommendations. The same thing happens in medical schools. My recommendation to any pharmacy students reading this is to go one step further than memorization; try to understand why things are being recommended. That goes for anything you read here as well. It might be that your patient doesn't fit in the same box, a new study came out after the guideline/article was written, the author(s) made decisions that you disagree with given the supporting data, or any number of other circumstances that invalidate the recommendation. Guidelines are written by people, and they're just like everyone else: capable of making mistakes.