The Heart Supplements I Recommend to Family

This letter brings together dozens of deep dives, clinical trials, and mechanistic papers to identify the most interesting, and evidence-based, heart health supplements that you can consider today.

My heart should be riddled with cardiovascular plaque.

I should be having heart attacks like rabbits have babies.

For most of the last seven years, my total cholesterol has hovered around 700 mg/dL. I also have a history of inflammatory disease (ulcerative colitis), my Lp(a) is 194 nmol/L, and my father had a cardiovascular event in his 40s.

In other words, things should not be looking great for me.

And yet, what I’ve found is the opposite: my heart is perfectly clean.

Not only am I asymptomatic, but on advanced cardiac imaging, my plaque burden is zero.

And when I say zero, I mean zero—after expert review of my coronary CT angiography for both calcified and non-calcified plaque, plus an additional AI-guided quantification designed to detect plaque down to the lowest cubic millimeter, I have 0 mm³ of plaque in my coronary arteries.

Now, yes, you could say I’m young—I turned 30 on November 3, 2025. But keep in mind: the patients with homozygous familial hypercholesterolemia, the genetic disorder whose study helped catapult LDL cholesterol into its role as cardiology’s chief villain, often had LDL and total cholesterol levels similar to my own, and were developing severe disease and having heart attacks by as young as age 10.

So, it is genuinely remarkable that I have no plaque. The reasons why are manifold. My overall good metabolic health. The physiological reason my LDL is high in the first place. And so on.

And while I certainly won’t chalk up my pristine coronary arteries to supplements, nor use my story as a lever to sell you products, my medical history has inspired a deep curiosity about everything I can do to protect my heart while supporting my overall health at the same time.

That is the purpose of this letter: to review, with rigor and precision, supplements that may support heart health through different mechanisms—and to clarify who might benefit most from what.

For example, compound #1 may offer particular advantages to someone with high blood pressure; compound #3 may make more sense for someone on statins; compound #5 for people with high Lp(a); and compound #6 may have unique relevance for people with a second X chromosome.

Author’s aside: What This Letter Is and Is Not

Before we begin, I want to clarify what this letter is, and what it is not. This is not AI slop. This is not me leveraging credentials or personal story to sell you anything other than information.

This is a synthesis of dozens of studies I’ve read, printed, marked up, and deeply processed; work I’ve discussed with colleagues in journal clubs and interviews, with evidence throughout via hyperlinks to prior deep dives (just click on the section headings) totaling tens of thousands of words.

In the end, you can decide whether this is trustworthy. But in a world of information overload, my goal is simple: to make what follows concise and high-quality. Go as deep as you’d like.

Now, let’s go on a journey of nuance, precision, rigor, and curiosity—all in the service of learning how to better protect your heart.

Nattokinase

One of the more intriguing compounds in the cardiovascular space comes from an unlikely source: nattō, a traditional Japanese fermented soybean food that has been consumed for over a thousand years.

Beyond its distinctive smell and texture, nattō has long been associated with longevity and cardiovascular health. In large observational studies, individuals with the highest intake of nattō have shown significantly lower rates of cardiovascular mortality—on the order of ~25% lower risk compared to those consuming the least.

*Higher nattō intake is associated with a 25% reduced risk of cardiovascular morality (hazard ratio 0.75). This effect appears specific to nattō and does not generalize to other soy-based products.

Now, observational data always raise the question of confounding.

Perhaps nattō eaters are simply healthier in other ways. That’s a fair concern.

But what makes this signal particularly interesting is that the benefit appears specific to nattō, not to soy intake more broadly. Other soy foods do not show the same association. Curious… That suggests there may be something unique about nattō itself.

Enter Nattokinase.

Nattokinase is an enzyme produced during the fermentation process by Bacillus subtilis. And it may be one of the key drivers of nattō’s cardiovascular effects.

In one large human study involving over 1,000 participants, individuals taking high-dose Nattokinase (10,800 fibrinolytic units daily) for one year showed something striking: regression of atherosclerosis.

Using ultrasound imaging of the carotid arteries, researchers observed:

• A ~22% reduction in carotid intima-media thickness (CCA-IMT)

• A ~36% reduction in coronary plaque surface area (CPS)

Those are not trivial changes. They suggest not just slowing of disease progression, but potential reversal.

In addition, participants experienced:

• ~16% reduction in triglycerides

• ~18% reduction in LDL cholesterol

• ~16% increase in HDL cholesterol

Now, to be clear, this was not a randomized controlled trial, and participants were compared to their own baseline. So, we cannot definitively attribute causality.

But the magnitude of the effect, combined with the biological plausibility, makes this signal difficult to ignore.

Let’s double click on that term, “biological plausibility.” Effectively, I’m just saying a mechanism with extra syllables—because that’s how we scientists do.

Pneumonoultramicroscopicsilicovolcanoconiosis anyone?

Yes, that’s a real word you learn in medical school. And apologies to anyone with hippopotomonstrosesquippedaliophobia for the jump-scare. (That’s the medical term for fear of long words.)

Okay, back on track!

How might Nattokinase be working?

Broadly, its effects can be grouped into three categories.

1. Anti-thrombotic activity

Nattokinase has what’s called fibrinolytic activity—it helps break down fibrin, the structural “mesh” that stabilizes blood clots. It also enhances the body’s natural clot-dissolving system by increasing tissue plasminogen activator (tPA) and reducing its inhibitor, PAI-1. On top of that, it appears to reduce platelet aggregation. Taken together, this shifts the balance away from clot formation and toward clot breakdown.

2. Blood pressure regulation

Nattokinase appears to inhibit angiotensin-converting enzyme (ACE), a key regulator in the renin–angiotensin system. By reducing ACE activity, it may decrease vascular constriction and lower blood pressure.

This effect has been demonstrated in randomized controlled trials.

In one such study, participants taking 2,000 fibrinolytic units daily experienced modest but meaningful reductions in both systolic and diastolic blood pressure—comparable to what might be achieved through structured dietary interventions.

3. Reduction in oxidative stress

Oxidative stress plays a central role in vascular damage, inflammation, and atherosclerosis. Nattokinase may help by upregulating endogenous antioxidant systems, protecting blood vessels, and reducing lipid oxidation.

*Mechanisms by which Nattokinase can improve cardiovascular health: by reducing blood clotting, reducing blood pressure, and reducing oxidative stress.

Stepping back, what makes Nattokinase compelling is not just any one of these mechanisms, but the convergence of effects: It influences clotting; It influences blood pressure; It influences vascular health at the biochemical level.

And, at least in preliminary human data, these effects translate into meaningful clinical changes.

But here’s the catch…

The difference between something being “interesting” and actually working often comes down to how it’s used. So, this is where things get practical: dosing.

In the rest of this letter, we’ll cover how to actually apply these ideas, not just for Nattokinase, but for 5 additional supplements. We’ll walk through how to":

• Influence ApoB naturally

• Reduce inflammation inside your arteries

• Offset some of the metabolic harms of statins

• Reduce or eliminate risk associated with high Lp(a)

All of this is grounded in the scientific literature, with links to deep dives in the section headings and throughout so you can vet everything as thoroughly as you’d like—along with specific protocols, dosing strategies, and who stands to benefit most from each intervention.

If you haven’t yet joined the premium community, I invite you to do so now, and discover why members call it the best $8 they’ve ever spent on their health, “an oasis of nuance on the internet,” and “an intellectually stimulating environment unlike anything else.”