DON'T STOP AT LDL IN PREVENTING CARDIOVASCULAR DISEASE
I talk a lot about LDL, ApoB, and their causal role in atherosclerosis. But there's another side of this equation that deserves just as much attention: the health of the endothelium, or the delicate lining of our blood vessels.
Think of ApoB-containing lipoproteins, the main one by far being LDL, as the wood feeding the fire of atherosclerosis. Because "sparks" are inevitable in all human bodies, the more wood (LDL/ApoB) available, and the longer it's there, the greater the opportunity for fire (plaque) to develop.
But what about the environment within which the fire may or may not start?
In other words, what about the endothelium?
Its health influences vascular function, inflammation, blood clotting, and many of the processes that determine how atherosclerosis develops and progresses. While ApoB retention is central to plaque initiation, the condition of the vascular environment can profoundly influence what happens next, and potentially even the rate of ApoB retention itself.
And interestingly, there's another connection here. Elevated LDL itself can impair endothelial function, even apart from its role in plaque formation. So the relationship can work in both directions: more LDL can contribute to a less healthy vascular environment, which in turn may further promote ApoB retention and plaque development.
In other words, the wood itself can help make the fire pit more vulnerable to fire.
WE NEED TO ADDRESS BOTH SIDES OF THIS EQUATION.
Here's where nutrition gets particularly interesting. A major 2025 meta-analysis in the American Journal of Clinical Nutrition examined 133 randomized controlled trials investigating the effects of foods and dietary patterns on endothelial function, primarily using flow-mediated dilation (FMD), a measure of how well arteries respond to increased blood flow.
The findings were fascinating.
Fruits, vegetables, soy foods, nuts, seeds, cocoa, and tea all demonstrated improvements in endothelial function. Mediterranean dietary patterns also showed significant benefits.
Egg consumption showed a small negative effect, while other research suggests dairy is mostly neutral or sometimes beneficial. The evidence for individual meats and fish is more limited or mixed. The researchers were also clear to point out that a lot of the research in this area is of low to moderate certainty, so we can only draw so much directly from it.
However, there's also a substantial body of research showing that high-fat meals can temporarily impair endothelial function, although the magnitude depends on several factors, including fat type, total fat load, the accompanying foods, and the individual's metabolic health.
AND THIS IS ONE REASON I'M CAUTIOUS ABOUT LOWER-CARB, HIGHER-FAT DIETS, EVEN WHEN THE FATS ARE MOSTLY UNSATURATED.
When we eat a high-fat meal, circulating triglyceride-rich lipoproteins increase for several hours. This postprandial state can be associated with oxidative stress, altered nitric oxide signaling, and transient reductions in endothelial function.
And if someone is eating high-fat meals two or three times every day, it's reasonable to ask whether repeated postprandial lipemia could have consequences for endothelial health over time, even if those meals contain mostly unsaturated fats.
Now, this doesn't mean that olive oil, nuts, or other unsaturated fat sources are equivalent to saturated fat, or that every high-fat meal causes endothelial dysfunction. In fact, nuts and Mediterranean dietary patterns have demonstrated vascular benefits in clinical trials, and some studies suggest that unsaturated fats may be considerably less disruptive than saturated fats.
But it does raise a question I think deserves more attention: Even if the types of fat we're eating are relatively healthy, could repeatedly consuming large amounts of fat throughout the day still be less than ideal for someone trying to aggressively treat existing atherosclerosis?
We don't yet have the long-term clinical outcomes evidence to answer that definitively. And importantly, transient postprandial changes in FMD don't necessarily translate into greater plaque progression or more cardiovascular events.
Still, when treating someone with substantial coronary disease, I think it's a reasonable consideration, and another reason I tend to favor a relatively low-total-fat, whole-food, plant-based approach over one that relies heavily on added oils and large amounts of high-fat foods.
So what happens when we put all this together?
THE DIET THAT MAY BE MOST EFFECTIVE AT TREATING ATHEROSCLEROSIS IS ONE THAT MAXIMIZES THE FOODS THAT SUPPORT ENDOTHELIAL HEALTH WHILE MINIMIZING THOSE THAT MAY IMPAIR IT.
This is where I think the severity of someone's cardiovascular disease should influence how aggressively we approach nutrition. For someone at relatively low risk, who is more in "prevention mode" rather than "treatment mode," eating a predominantly plant-rich Mediterranean style of diet would very likely be an excellent approach.
But, for someone with established coronary artery disease, and especially someone with substantial plaque burden, or particularly high cardiovascular risk, why wouldn't we want to push the nutritional intervention further?
To get the best possible results, we would want to a) maximize foods with demonstrated vascular benefits, b) minimize foods that are relatively neutral, and c) avoid foods with evidence of harm, especially when healthier alternatives are available.
THAT'S WHERE A WELL-DESIGNED, WHOLE-FOOD, PLANT-BASED DIET MAY HAVE ITS GREATEST ADVANTAGE.
Think about it for a second.
A diet centered on vegetables, fruits, legumes, intact whole grains, and other minimally processed plant foods provides an enormous variety of fiber, polyphenols, antioxidants, nitrates, and other compounds that may support vascular function.
At the same time, especially when designed to be low in saturated fat, it can substantially reduce LDL cholesterol and ApoB. Plus, if also relatively low in overall fat, it may reduce the amount of fat surging into the bloodstream after a meal (postprandial lipemia), which can potentially offer even more benefit to endothelial health.
In other words, back to our fire analogy, this dietary approach is essentially improving the condition of the fire pit AND removing much of the wood feeding the fire.
That's a pretty powerful combination.
To be clear, that's not to say we know for sure that lower total fat is always better, regardless of what replaces it. But it's interesting to note that the dietary interventions used by Morrison, Pritikin, McDougall, Esselstyn, and Ornish, all of which produced highly encouraging cardiovascular results, shared two important features: very low saturated fat AND relatively low total fat. How much each of those contributed to their results remains an open question, but it's another potential benefit worth considering, especially when someone's lipid levels and other cardiovascular risk markers improve with this approach.
Also to be clear, the meta-analysis above does not definitively prove that a strict whole-food, plant-based diet is superior to a Mediterranean diet for endothelial function. We don't have enough direct head-to-head evidence to establish that. And there may be reasons why for some people, a Mediterranean diet is a better overall approach, whether or not it was the absolute best way to eat for artery lining function.
However, the totality of evidence does still make a compelling case for studying and using more intensive, at least plant-rich nutrition, especially in people with established disease.
And again, the Mediterranean findings are very encouraging too, especially when we consider versions of it that emphasize vegetables, legumes, whole grains, and other plant foods, with minimal saturated fat and dietary cholesterol. The so-called Green Mediterranean diet is especially interesting here, but again there is still more to learn.
HERE'S THE GOOD NEWS: IT DOESN'T HAVE TO BE ALL OR NOTHING.
If someone isn't ready to eat a completely whole-food, plant-based (WFPB) diet, they can still eat that way for many or even most of their meals and likely derive significant benefits.
Imagine, for example, eating WFPB breakfasts and lunches every day, along with several WFPB dinners each week. Then, for the remaining meals, following a very plant-rich, low-saturated-fat Mediterranean pattern.
That's a tremendous amount of high-quality nutrition, and potentially gets someone quite close to the overall dietary pattern we're aiming for, and perhaps even close enough that the actual goal of stabilization and possible reversal of some plaque can be attained.
MORE EVIDENCE TO CONSIDER
When we zoom out even further, this all starts connecting some very interesting dots.
Let's consider, for example, traditional populations of people with historically very low rates of coronary heart disease. Their diets weren't identical, and were not completely vegan, but many of the best-studied groups of people emphasized minimally processed plant foods, high fiber intake, and relatively low saturated fat.
Then consider the decades of clinical observations and interventions from physicians and researchers such as Lester Morrison, Nathan Pritikin, John McDougall, Caldwell Esselstyn, and Dean Ornish.
They all took slightly different approaches, recommended different degrees of dietary restriction, and all of their studies (like so many in nutrition) had some limitations. But what is quite clear is the remarkable amount of common ground they still shared: They all recommended diets centered on minimally processed plant foods, generally low in or absent of animal foods and especially saturated fat.
Collectively, their work reported substantial improvements in cardiovascular risk factors and symptoms, with some interventions also demonstrating improvements in measures of coronary atherosclerosis, including regression in selected patients. Of course, the strength of the evidence varies considerably across these studies.
Then again consider the much larger body of observational and clinical trial evidence supporting plant-rich Mediterranean dietary patterns for cardiovascular prevention.
These aren't all equivalent forms of evidence, and we shouldn't pretend they prove the same thing. But they do point in a broadly consistent direction.
THE MORE SERIOUS THE DISEASE, THE STRONGER THE RATIONALE FOR USING THE MOST INTENSIVE, EVIDENCE-INFORMED NUTRITIONAL APPROACH WE CAN SUSTAIN.
To be clear, none of this means nutrition replaces lipid-lowering medications or other evidence-based treatments, when indicated. Quite the opposite actually. For someone with established ASCVD, combining intensive nutritional changes with appropriate lipid-lowering therapy likely offers complementary benefits that make for an even more powerful effect.
However, it should also be acknowledged that, at least in some cases, there is evidence suggesting that when someone is very thorough and consistent with their dietary (and other lifestyle) changes, plaque stabilization and even regression may be possible without medications. That doesn't establish that medication can safely be omitted in patients for whom it is indicated.
We don't yet know whether strict WFPB nutrition is superior to an optimized Green Mediterranean diet for cardiovascular events, and I wouldn't try to definitively claim it is.
But when I am just thinking logically, considering the evidence on ApoB, endothelial function, plant foods, intensive dietary interventions, and cardiovascular outcomes together, AND looking at the experiences of my patients from my own practice, I think there's a very strong biological and clinical rationale for making a minimally processed, low-saturated-fat, relatively low-total-fat, plant-centered diet the foundation of aggressive nutritional treatment.
For those willing and able to take that approach all the way to WFPB, I think there's a reasonable argument that it may be among our most powerful dietary strategies. If not, you absolutely may still be able to do plenty enough to control your situation very well.
LESS WOOD + AN ANTI-FIRE ENVIRONMENT = SMALLER FIRE.
