It’s been ten years since I wrote about lowering cholesterol, so it seemed like a good time to revisit the topic. I started with three sentences: “There’s reason to question the cholesterol hypothesis’ – that cholesterol is the Big Bogeyman for heart disease. This paper won’t get into that. Suffice it to say, cholesterol may not be quite as important as you think.”

I figured that was enough. I’d pay lip service to the question, breeze past the controversy, and discharge my responsibilities to truth, transparency, and disclosure without much heavy lifting – and then I’d jump right in to talking about herbs you could take.

But then I looked at the science. And I realized those three sentences weren’t going to cut it. A lot has come into sharper focus the last ten years. What could have reasonably been labeled a “controversy” then has become much less controversial now, as paper after paper is published showing that simply lowering cholesterol has very little impact on disease progression, and meaningful endpoints like heart attack and stroke. I’m not saying the issue is settled – that it’s 100% black-and-white – that cholesterol doesn’t matter at all. But I am saying that cholesterol as an independent risk factor for heart disease has been grossly exaggerated; the risk reduction in reducing cholesterol has been vastly overstated.

Most of us have heard of the studies where cholesterol-lowering drugs have underperformed over the years. If you haven’t, I’ll put a few links in the footnotes, to summarize that research¹.

But (I hear some of you ask) that’s the pharmaceuticals – what about the natural stuff? Sure, there are a number of herbs that lower cholesterol. And if you want them, we’ve got them. But what I’m trying to say is that lowering cholesterol without addressing underlying issues should not be our primary goal².

So, if all that’s true, how could we have been so wrong, for so long? Simply put, we confounded and conflated a lot of things: dietary cholesterol with blood cholesterol; correlation with causation; markers with endpoints. We oversimplified everything. AND, some of the research may have been a little questionable, too.

Correlation vs. Causation

As far back as the 1950s, we knew that people with more cholesterol in their blood had higher rates of heart disease. We realized that atherosclerotic plaques – the fatty deposits that caused hardening of the arteries – were made of cholesterol. There was a link between cholesterol and heart disease. But a lot of things are “linked.” For example, band-aids and scars are both linked to skin injuries. But that doesn’t mean either of them cause skin injuries, or that I could reduce skin injuries by eliminating band-aids and scars. Band-aids are “linked” to skin injury as a marker; scars as an effect. Neither one is a cause.

Cholesterol has a similar relationship to heart disease.

To be clear, this isn’t just me talking. Thirty years ago, Linus Pauling suggested that cholesterol was actually a repair mechanism to patch worn-out blood vessels, sort of like glue patches a leaky bicycle tire. Sure, cholesterol leads to atherosclerotic plaque. But that’s better than loss of blood vessel integrity.

Dietary vs. Blood Cholesterol

One of the most problematic oversimplifications has been to conflate dietary cholesterol with blood cholesterol. Hard-boiled eggs, for example, are packed with cholesterol. But eating them barely raises blood

cholesterol. Meanwhile, sugar is cholesterol-free, but it can raise your blood cholesterol very significantly. We’re going to talk a lot more about sugar later….

Confounders in Nutrition Research

Nutrition research is always tough because confounders are such a problem. For example, let’s look at deli meats. People who eat bacon, cold cuts, and sausage are more likely to have heart disease. And as we know, these meats are packed with cholesterol. The connection seems clear. But let’s look deeper. These meats (if they’re from poorly raised animals) are also loaded with pro-inflammatory fats like arachidonic acid. They tend to be full of preservatives. People who eat deli meats eat more unhealthy food in general; they eat fewer fresh fruits and vegetables. There’s a correlation between deli meat consumption and low SES (socioeconomic status). (As we know, there is a causal relationship between wealth and health). So yes, eating more cholesterol is linked to worse outcomes. But is it the cholesterol?

Problems with the Clinical Trial Data

Where the rubber meets the road in medical research is actual clinical trial data. You give some people a medicine, you see what happens. Everything else is theory.

Many of the original studies on cholesterol-reducing drugs demonstrated significant benefits. Subsequent research, less so… It has been suggested this can be explained by following the money. The more positive, initial trials are almost always industry-funded; the follow-ups, funded independently or by government.

The links in the first footnote summarize a lot of this data. But I wanted to call out a recent study that drives the point home for me. “Evolucumab and clinical outcomes in patients with cardiovascular disease” was published in the New England Journal of Medicine in 2017. This paper reports on 27,564 patients taking either taking just a statin, or a statin plus an additional cutting-edge cholesterol drug, for 48 weeks. The authors conclude that the cutting-edge drug significantly reduces heart disease risk.

We’re going to dig a little deeper. LDL-C (so-called “bad cholesterol”) was lowered by 59%. That’s huge! But that 59% drop in the marker led to only a 1.5% reduction in cardiovascular events. That’s not much. But it’s not nothing, either. 219 fewer people had heart attacks, strokes, etc.

But we’re going to dig deeper still. That was a 1.5% reduction in total cardiovascular events. Let’s look at fatal cardiovascular events. There was a slight increase in cardiovascular deaths in the treatment group (251 vs. 240), as well as in increase in deaths from all causes (444 cs. 426). These numbers were too small to be considered statistically significant, so they weren’t really reported. You have to dig into the charts to see them.

Again, bear in mind this study was announced and reported as a great success, by the study authors, the medical journal, and the press – even though not a single life was saved. Even though, at around $14,000 a year, the cost of preventing a single (non-fatal!) event was roughly $900,000. (The drug company, Amgen, has since lowered the cost of the drug 60%). The study was funded by Amgen. Most of the authors received “speaking” or “consulting” fees from, or were direct employees of, Amgen.

So, are you saying we shouldn’t try to reduce cholesterol at all?

Of course none of this means we shouldn’t try to reduce our cholesterol holistically. If cholesterol is a marker for underlying health issues, effectively lowering that cholesterol can be good marker for when we’re addressing those issues. So, if you lower it through exercise, or shifting to an anti-inflammatory diet, or quitting smoking, or reducing sugar, that means something. But lower it by just taking a drug – without addressing why cholesterol is high in the first place – your real-world results are going to be questionable at best.

So, what does cause heart disease (and what can we do about it?)

Insulin-resistance is the prime culprit. I’m not saying it’s the only culprit. But almost everything else we can point to as a risk factor – high blood pressure, chronic inflammation, LDL:HDL ratio, obesity – overlaps with insulin resistance in some way. It’s in the middle of the Venn diagram. It’s the central culprit.

We’re going to talk a lot more about insulin resistance next month, plus the food, herbs, and supplements that can fix it. Can’t wait a month? In the meantime, eat more healthy dark-colored, high-fiber foods with healthy fats; exercise reasonably; and cut back on the junk.

1. Three analyses of statin performance can be found on one of my favorite sources for thoughtfully parsed and honestly summarized research, theNNT.com. I love the NNT! They simplify and they clarify, but they don’t ever dumb down. Check out https://www.thennt.com/nnt/statins-persons-low-risk-cardiovascular-disease/ and https://www.thennt.com/nnt/statins-for-heart-disease-prevention-without-prior-heart-disease-2/, which explore statins given to people at low risk or without known risk for heart disease. In both cases, the drugs do more harm than good. Here https://www.thennt.com/nnt/statins-for-heart-disease-prevention-with-known-heart-disease/, statins were given to people with known risk, and they did more good than harm. Https://www.amjmed.com/article/S0002-9343(18)30404-2/fulltext is a summary of the larger issues.
2. That being said, most of the natural stuff does more than just lower cholesterol. Depending on the herb or vitamin, it can work through improved liver function, better blood sugar metabolism, calcium metabolism, etc….