Most Everyone Has Plaque

The Way of Life

Would you subject yourself to chemotherapy if you found out you had one cancer cell? How about 100 cancer cells? 1000? A million cancer cells? How about a billion cancer cells? Cancer becomes detectable typically at a billion cells. Stage 1.

Would you take insulin if you found out you were insulin-resistant? How about if you were pre-diabetic? How about if you were a Type II diabetic? It takes decades to develop insulin resistance. The average time to go from full insulin resistance to a diagnosis of diabetes is 13 years. Once someone is pre-diabetic, the average is ~ five years to diabetes.

What if I told you that if you are over the age of twenty, there is a 77% likelihood that you have plaque growing in your arteries?

If you are over fifty, then you have 91% likelihood.

The plaque will grow and grow year by year until it occludes your arteries. That is what the data has declared again and again over the past seven decades. The average age of a heart attack in men is 61 and in women, 71. And it is the global #1 killer. 20 million people a year.

I’m on this hit list, but I am learning how to get myself off it.

Food for thought. This newsletter is a long one, but I think it is so important that I’m not going to edit it down to half the usual length I write.

The Scan

I got a calcium heart scan because my close friend, Rob died suddenly of a heart attack at 58. Super fit. Seemingly healthy. No warning had been communicated to him. Just gone, with the abruptness that only the cardiovascular system can manage, before any of the conversations that were supposed to happen. I am a physician. I left clinical medicine in 2000, thinking I’d build an Internet company for three to six months. I wanted to do health as philanthropy and make $ on the Internet. It’s been 25 years, but the physician’s mind does not leave, and what it does with grief is turn it into a question. First: Why Rob? Now: Why me? And who else? What happened?

A calcium score of 505 means significant atherosclerotic burden. Your coronary arteries have been accumulating calcified plaque for long enough that a CT machine can measure the mineral deposits and assign them a number. A score above 400 places you in the highest risk category. A likely heart attack in the next two to five years. Ominous. The standard response in conventional cardiology is statins, aspirin, and watchful management of a disease that will continue to progress.

My first thought, shocking and surprising, was that it must be my extreme cycling. I had been riding the North Shore mountains aggressively for a decade, covering up to 7,000 kilometres and gaining 100,000 meters of elevation per year. I was familiar with the literature on extreme endurance athletes and coronary calcification. I wondered whether I had done this to myself. Rob was also an athlete, climbing the Matterhorn three times. Extreme.

I sat on the ledge of my bathtub at two in the morning as I prayed and pondered my results and my future. I had so many questions that I could not answer. How could this be? Then a revelation.

In my few spare moments, I read scientific and medical research studies. The autopsy studies. Mice studies. Human studies. The food studies. The biochemical pathways. Before, I had a hard time remembering the differences between LDL and HDL. Now I feel like they are my close friends. The PDAY data. The Bogalusa Heart Study. I now have a good, high-level overview of what happens to us over the decades.

Why wasn’t this being taught in medical schools? In books? In the news? Why didn’t I ever hear this?

If I hadn’t been exercising, I would likely not be here right now.

It started when I was a teenager.

The Carefree Teenager

I grew up eating fried food. A lot. In my thirties, I became health-aware. I was eating organic. But I loved Korean and American fried chicken, tempura, the crisp oil-saturated foods that felt like pleasure and were, at the cellular level, a sustained assault on the endothelial lining of every vessel in my body.

The autopsy literature is unambiguous about when plaques begin. The Bogalusa Heart Study found fatty streaks in the coronary arteries of half the children between the ages of two and fifteen. The Korean War autopsies of 1953 found gross coronary atherosclerosis in 77% of soldiers with an average age of 22.1 years. My calcium score of 505 was not the product of five years of cycling up mountains. It was the product of four decades of compounding plaque buildup.

Here is what cycling had actually done: it built collateral vessels. Natural coronary bypasses. When a coronary artery narrows progressively, the body grows alternative routes. Small vessels enlarge and reroute the blood supply. This is why I could ride at the intensity I rode, why I was in the best aerobic shape of my life at 55, and why my CT showed multi-vessel coronary artery disease simultaneously. The cycling had not caused the disease. It had made me functionally elite despite it.

I had the arteries of a man heading for a cardiac event in the next two to five years. I also had the cardiovascular capacity of a competitive athlete. I rode with the fastest in the city. How could both be true at the same time?

The Logic of Choice

A June 17 CT angiogram confirmed multi-vessel disease: 77% obstruction in the D1 coronary artery, 55% in the Ramus Intermedius vessel, and significant disease in all vessels. Traditional cardiology had a clear pathway: a stent for the 77% lesion, statins, aspirin, and regular monitoring. Standard of care. Evidence-based. And, as I thought about it that night, obviously insufficient.

If I stented the 77% vessel, I would fix one obstruction in a system where multiple vessels were diseased, while the underlying biological process continued to run. The 55% obstruction would continue toward 70%, the conventional threshold for the next intervention. I was 55 years old. On the conventional trajectory: two stents, then three, then a bypass conversation in my sixties.

I thought about Dr. Caldwell Esselstyn, a former Cleveland Clinic surgeon, Phi Beta Kappa from Yale, Olympic gold medalist in rowing, who spent the second half of his career reversing coronary artery disease through diet alone. One of his patients arrived with 100% occlusion of a major coronary artery. At 32 months on the protocol, the angiogram showed complete resolution. The vessel had reopened. He’s a healthy 92-year-old still preaching his gospel to reverse heart disease through an oil-free, whole food, plant-based diet. I am very grateful that he has explained why such a simple remedy works. It’s so simple, people will gloss over it. I did so as well, even after listening to his lectures dozens of times. I am rereading his book again with a new lens. How foolish we can be.

I adopted the Esselstyn protocol: whole food plant-based diet, fat held below 25 grams per day, no oils, no animal products.

Then, after month one, I added to this foundation diet and layered fasting: 16 to 8 daily, one OMAD (one meal a day) weekly, and 2 to 3 days fast monthly.

The HIIT cycling continued, now understood as a targeted delivery of nitric oxide to every coronary endothelial cell with every pedal stroke. My pressure washes for the arteries, once I had established the right biochemical environment for my arteries.

And a synergy stack: Vitamin K2 MK-7 from natto with its nattokinase, fresh garlic, black garlic and aged garlic extract, pomegranate juice, green tea tablets and green tea, 1g of omega-3 fatty acids.

Full Reversal in Just Three Months

The carotid ultrasound at three months showed something I had hoped for but had not been certain enough to expect: both carotid arteries were completely clear. Not reduced. Clear. The plaques had resolved bilaterally in just three months. And the CIMT, the intima-media thickness that had read like an 85-year-old when I started, crossed into high-normal for age 55. By month ten, it was mid-normal. A 53% bilateral reduction in carotid arterial wall thickness, confirmed on imaging another three times afterwards, always improving.

My arterial age dropped 30 years in just 3 months.

The coronary picture is different. The D1 stenosis at 79% (slight increase from 77% and likely just measurement difference) on structural CT imaging. But the CT-FFR, the measure of actual blood flow past the obstruction, improved from 0.75 to 0.80. The pipe looks the same. The river is flowing better. Something is changing in the functional architecture of the vessel before the structural regression becomes visible on imaging. But I was still extremely disappointed that the coronary arteries didn’t regress like the carotids. Why not?

I felt delighted at the carotid result. And underneath the delight, the quieter pressure of a much larger question.

Why the Carotids and Not the Coronaries?

I wondered about this for months. Both carotid plaques had vanished on imaging in three months. The coronary plaque had not moved structurally, though the FFR had improved from 0.75 to 0.80, from a stentable reading to a low-normal one. Something was changing in the coronary territory. But not the same thing, and not at the same speed.

I had three hypotheses, and I turned each one over during my long therapeutic rides through the North Shore.

Hypothesis #1: Vessel geometry and flow mechanics.

The carotid arteries are relatively straight vessels that carry blood upward to the brain, with blood flow predominantly in a slower, laminar pattern. Laminar flow is protective: it delivers smooth, directional shear stress to the endothelium, which upregulates eNOS and nitric oxide production. The coronary arteries, by contrast, are small, curved vessels with multiple bifurcations and bends, where flow becomes turbulent and oscillatory at every curve. Turbulent flow creates the low-shear-stress environments that damage the endothelium and invite lipid deposition in the first place. The same turbulence that built the plaque may be slowing its reversal. I had to be prescriptive in my HIIT rides up mountains. I do that by throttling my heart rate to 150 bpm. Temporary rises to 170 bpm, I ease off. My Gran Fondo ride of 125 km last June 8 clocked my heart rate at 172 average for the 4 hours and 18 minutes. And I thought I was taking it easy. My heart was working extremely hard. At that time, I did not yet know the full extent of my disease. Now I do.

Hypothesis #2: Vessel diameter.

The carotid arteries are substantially larger in diameter than the coronary arteries. A larger vessel means a given plaque volume represents a smaller fraction of the total wall. The reverse cholesterol transport machinery, the HDL particles and macrophage efflux mechanisms that extract cholesterol from the plaque, must work through a smaller absolute lipid burden relative to vessel size in the carotids than in the coronaries. In a small coronary artery, even a modest plaque represents an enormous proportion of the vessel wall. The biology has less room to work.

Hypothesis #3: Plaque age.

This was the one that felt right from first principles. The ASAP study establishes that coronary disease develops earlier in life than carotid disease. The carotid territory follows the coronary in the anatomical sequence of progression. If the carotid plaques arrived later, they were younger lesions: softer, more lipid-rich, less fibrotic, less calcified, more biologically mobile. Young plaque reverses the way young bone heals, faster and more completely than older, denser, more mineralized tissue. My coronary plaques have been building since my teens. My carotid plaques began in my forties. Three decades of additional compounding had made the coronary lesions structurally different and much harder to reverse. Joe Crowe’s reversal happened at 44.

And then the calcification data settled it.

My coronary artery calcium score of 505 confirmed what first principles suggested. Two-thirds of my coronary plaque burden is calcified, Stage 5 in the AHA classification, the equivalent of mature rock. These are lesions that began accumulating calcium in my thirties and forties. The outer shell has mineralized. They are not going to dissolve in three months. They may not dissolve in three years. The biology of calcified plaque reversal is not the biology of soft plaque reversal.

But here is what I also concluded: the non-calcified third of my coronary plaque is still Stage 3 to Stage 4, still lipid-rich, still biologically active, still operating by the same rules that cleared my carotid arteries. Smaller vessels, older lesions, more demanding mechanical environment, yes. But the same reverse cholesterol transport mechanisms, the same nitric oxide pathway, the same eNOS upregulation from cycling, the same DDAH protection from pomegranate and EGCG. The biology does not change. Only the timeframe does.

My realistic expectation: 12 to 24 months to clear the non-calcified coronary component. And for the calcified component, not dissolution but stabilization, depleting the lipid core beneath the calcium so that what remains is an inert mineral shell in a vessel that flows freely. Think of it like osteoporosis in reverse: the mineral remains, but the biological danger inside it is gone.

I expect my coronary FFR to continue improving as the soft plaque recedes. The CT angiogram in June 2028 will either confirm this or refute it. I will report my thoughts and metrics weekly, with labs every 6 weeks and CT scans twice a year.

Where Else?

If the carotid plaques resolved in three months, when did they develop? If they developed, what was happening simultaneously in my coronary arteries, which the autopsy literature says accumulate disease earlier in the anatomical sequence? And if both territories carry disease that began when I was a teenager, what is happening right now in the arterial territories I cannot imagine with a simple ultrasound?

My cerebral vessels: the plaque that could embolize to my brain, the same pathway that put a clot in my father’s middle cerebral artery when he was 78, producing complete right hemiplegia, which he spent months recovering from. My father recovered 90%. I gave him high-dose green tea EGCG and omega-3 fatty acids from the first week, and the biology of both compounds supports recovery of that magnitude. That was in 2014 so I already knew how to reverse plaque. I didn’t realize how at that time, but now that I delve into the biochemical pathways, now I see.

My mesenteric arteries feeding the intestine. My femoral arteries feeding my legs, where I have never felt claudication because the collateral circulation has not yet reached its limit. My thoracic and abdominal aorta, where atherosclerosis weakens the arterial wall and produces aneurysmal dilatation that kills without warning when the wall gives way. I watched a man die of this in the CT scanner when I was a medical resident on my surgery rotation.

And then, my eyes.

The Eyes Don’t See

On May 10, 2020, I was diagnosed with wet macular degeneration in my right eye. Wet AMD involves abnormal vessel growth beneath the retina driven by VEGF (vascular endothelial growth factor) signaling in a hypoxic, ischemic environment. It progresses rapidly. Ophthalmology considers it chronic and irreversible, managed with regular anti-VEGF injections directly into the eye. A major and severe cause of blindness. My prognosis? Most likely blind in years… unless I receive monthly anti-VEGF shots in each eye until I go blind.

I treated it as a retinal disease, which at its biological root it is. But it’s also a vascular disease. The choroidal vessels beneath the retina are subject to the same atherosclerotic and endothelial dysfunction processes as every other vascular territory. A retina deprived of adequate choroidal blood flow becomes hypoxic. Hypoxia drives VEGF. VEGF drives neovascularization.

Since beginning my REVERSAL protocol, my vision has been improving. The mechanism is coherent: if the protocol restores endothelial function and improves choroidal perfusion the way it restored my carotid arteries and improved my coronary FFR, the hypoxic signal diminishes and the neovascularization recedes. I did not have any eye shots at all for three years. I had to get one last December as I was so focused on my heart, but now that I understand better, my protocol treats both, 80% with the same foundational treatment and 20% more specific for the organ.

How many diseases that medicine treats as isolated organ pathologies are actually systemic vascular disease wearing different masks?

What the Autopsies Declare

The medical literature has understood the anatomical sequence of this disease for over seventy years, and has communicated it to the public with remarkable silence.

In 1953, pathologist William Enos (love his last name) published autopsies of 300 American soldiers killed in Korea. 

• Average age: 22.1 years. 

• Finding: 77.3% had gross evidence of coronary arteriosclerosis. 

The paper should have reoriented how medicine thinks and talks about cardiovascular disease. It changed very little.

Gerald Berenson spent 38 years tracking the children of Bogalusa, Louisiana. When cohort members died of accidents, he examined their arteries. Fatty streaks in the aorta: present in every individual. Fatty streaks in the coronary arteries: present in half of the children between the ages of two and fifteen.

Two years old!

The ASAP study, 3,400 autopsies across six arterial territories, confirmed the sequence: 

• abdominal aorta in the first decade of life, 

• then thoracic aorta, 

• then coronary arteries, 

• then carotid arteries, 

• then ascending aorta, 

• then cerebral arteries. 

By the sixth decade of life, 42% of individuals have Grade III coronary stenosis and 25% have Grade IV.

Everyone has this disease. Almost no one is told.

Why this Artery, Why this Stage?

The ASAP study did not just document that atherosclerosis is universal. It documented that it follows a fixed anatomical sequence with a precision that looks almost designed. The abdominal aorta before the thoracic. The coronary arteries before the carotid. The carotid before the cerebral. This sequence is not random. Each step follows from the physical mechanics of blood flow operating in that specific vascular territory.

The Six Arterial Territories in Order

1. Abdominal Aorta : First Decade of Life

The abdominal aorta is the first territory because it experiences the greatest oscillatory shear stress in the body. Blood leaving the heart travels as a smooth column through the thoracic aorta, but when it reaches the aortic bifurcation and the origins of the renal and mesenteric branches, the flow becomes turbulent and disturbed. Turbulent flow does not polish the endothelium. It damages it. Lipids accumulate preferentially at the outer walls of branches and at the posterior intimal surface, exactly where the PDAY study found the earliest lesions. It becomes critical when aneurysmal dilatation exceeds 5.5 centimeters, at which point the law of Laplace dictates that wall tension is proportional to radius: the wider the aorta, the more force trying to burst it open. Rupture is catastrophic and nearly always fatal within minutes.

2. Thoracic Aorta : Decades One to Two

The thoracic aorta is large in diameter and exposed to the highest pulse pressure in the body: it receives the full force of every cardiac ejection. The mechanical stress on the intima is enormous. But because the thoracic aorta is also large in diameter, the disease progresses for decades before it becomes flow-limiting. It becomes critical when atherosclerosis weakens the medial layer enough to permit aortic dissection, the catastrophic tearing of the inner aortic wall that allows blood to enter and propagate through the wall itself. Thoracic dissection can simultaneously shear off the coronary, carotid, and spinal arteries. It is survivable only with immediate surgery and kills approximately 50% of patients before they reach the hospital. This occurred to our good neighbour’s husband last summer. It’s devastating!

3. Coronary Arteries : Decades Two to Three

The coronary arteries are small vessels with a biologically unique environment: they are compressed with every heartbeat, experiencing systolic compression and diastolic perfusion in a cycle that repeats 100,000 times per day. The bending points, the bifurcations of the left anterior descending artery, the origins of the diagonal branches (that’s me 77% at D1), the curve of the right coronary artery, are where low and oscillatory shear stress creates the endothelial vulnerability that lipid deposition exploits. The LAD is the most commonly and severely affected coronary artery in every autopsy series ever published. It becomes critical at 70% stenosis, where the CT-FFR begins to fall below 0.80 and resting perfusion starts to be impaired. My D1 is at 77%. Below 0.75 the territory is ischemic at rest. My FFR is 0.80, low normal now in a 77% obstruction. Remarkable!

4. Carotid Arteries : Decades Three to Four

The carotid arteries develop disease after the coronary arteries in the anatomical sequence. The relative ease of carotid ultrasound and low cost make the carotids the clinical indicator of systemic arterial age. The disease concentrates at the carotid bifurcation, where the common carotid artery divides into the internal and external carotid arteries. At this bifurcation, the geometry creates a flow separation zone on the outer wall of the internal carotid where shear stress is chronically low, the exact condition that promotes endothelial inflammation and lipid infiltration. Carotid plaques are 70 to 90% lipid-rich, making them the most biologically active and the most responsive to reversal. They become critical when they rupture and embolize upstream, producing embolic stroke, or when they cause critical stenosis above 70% that reduces cerebral perfusion.

5. Cerebral Arteries : Decades Four to Six

The cerebral arteries are the last territory to develop significant disease because they are intracranial vessels with structural properties different from extracranial arteries: thinner walls, no external elastic lamina, and a different smooth muscle architecture. The blood-brain barrier environment also partially shields them from the systemic lipid and inflammatory burden that damages peripheral vessels. But once the upstream disease in the carotid and aortic territories is established, the cerebral arteries receive two simultaneous threats: in-situ plaque formation within the intracranial vessels themselves, and embolic disease traveling from the carotid and aortic territories. It becomes critical when it produces lacunar infarction from small vessel occlusion, or when a cerebral aneurysm at the branching points of the Circle of Willis ruptures, causing subarachnoid hemorrhage, with a mortality rate exceeding 50% in the first 30 days.

6. Femoral and Peripheral Arteries : Decades Four and Beyond

The femoral arteries develop disease later than the coronary and carotid arteries in the sequence, yet in adults they carry more total plaque burden than any other arterial territory: 76% prevalence compared to 45% coronary and 35% carotid in population studies. This paradox exists because the legs have extraordinary collateral vascular capacity that compensates silently for decades. It becomes critical at 60 to 70% stenosis when the collateral reserve is exhausted and claudication appears: ischemic cramping in the calf or thigh with walking that resolves with rest. Beyond that: rest pain, non-healing ulcers, gangrene, and amputation.

The Six Stages of Plaque

Think of the six stages of plaque the way oncologists think of cancer staging. Stage 1 breast cancer and Stage 4 breast cancer are different diseases wearing the same name. The staging communicates biological reality, urgency, and probability of reversal in a single number. Atherosclerotic plaque has never been routinely staged for patients. Medicine uses the phrase "coronary artery disease" as though it means one specific thing. It does not.

Stage 1: Fatty Streak

• Isolated macrophage foam cells accumulate in the intima. No structural disruption. No fibrous tissue. No lipid core. Lipid is entirely intracellular. 

• When: Childhood and adolescence. Present in every individual in an industrial diet culture. Bogalusa found it in two-year-olds. 

• Threshold: None. Fully reversible. 

• Reversal probability: Near 100% with dietary intervention.

Stage 2: Preatheroma

• Extracellular lipid pools begin to form. The arterial wall is thickening but no defined lipid core exists yet. CIMT begins to rise above age-expected norms. 

• When: Teens through early twenties in high-risk individuals. 

• Threshold: None, but this is the stage where CIMT imaging first becomes abnormal. 

• Reversal probability: Very high. The extracellular lipid pools are not yet organized into a necrotic core.

Stage 3: Soft Atheroma

• A confluent lipid-rich necrotic core has formed, covered by normal-appearing intima. No fibrous cap yet. This is the stage most vulnerable to rupture because a large lipid core behind a thin or absent cap is structurally unstable. 

• When: Late twenties through forties. This was my carotid plaque stage. Three months of the REVERSAL protocol cleared it completely. 

• Threshold: Rupture risk is high despite often modest stenosis. The 2018 SCOT-HEART data showed that low-attenuation plaque volume, the CT signature of this stage, is the strongest single predictor of heart attack, outperforming calcium score, stenosis severity, and every standard risk calculator. 

• Reversal probability: High. 70 to 90% with aggressive protocol.

Stage 4: Fibroatheroma

• A fibrous cap now covers the lipid-rich necrotic core. The plaque has organized into a two-layer architecture: lipid engine underneath, fibrous shield on top. Early calcification may be present. 

• When: Forties through sixties. 

• Critical threshold: The fibrous cap can thin and rupture, exposing the lipid core to flowing blood and triggering acute coronary syndrome. Thin-cap fibroatheroma with a cap under 65 microns is the architecture responsible for the majority of fatal heart attacks. 

• Reversal probability: Partial. The lipid core can regress through RCT (reverse cholesterol transport). The fibrous cap is more resistant to remodeling.

Stage 5: Calcified Plaque

• Dense calcium deposition within the necrotic core and fibrous cap. The plaque has mineralized. This is where my coronary disease currently sits, with a CAC score of 505. The calcified component is structurally more stable against rupture, but it is hemodynamically significant when it causes stenosis. 

• When: Fifties through seventies. 

• Threshold: Stenosis above 70% with CT-FFR below 0.80 indicates hemodynamically significant flow limitation. My D1 is at 77%, CT-FFR 0.80. 

• Reversal strategy: deplete the lipid core and macrophage burden inside the calcified scaffold, leaving an inert calcium shell. The calcium does not have to disappear for the threat to be neutralized.

Stage 6: Complicated Lesion

• Surface disruption, intraplaque hemorrhage, or superimposed thrombus. This is the plaque that has crossed the threshold into acute coronary syndrome. The fibrous cap has ruptured or eroded. The lipid core is exposed to flowing blood. Platelet aggregation and thrombus formation proceed within minutes. We call this a heart attack.

• When: Can occur at any stage but is most common at Stage 3 and Stage 4. Paradoxically, Stage 5 calcified plaques are more structurally stable and less likely to rupture acutely. 

• Threshold: This is the event. Myocardial territory is lost proportional to the duration and completeness of occlusion. 

• Reversal probability: The acute event cannot be reversed. But the remaining disease in every other vessel can be. Where you need to stent, bypass.

The most dangerous plaque is not the most calcified. It is the softest, most lipid-rich, least conspicuous lesion in the vessel wall, the one that does not restrict flow enough to cause a stress test abnormality, does not produce a high calcium score, and produces no symptoms until it ruptures.

The Life of the Flesh is in the Blood

I have read Leviticus 17:11 a hundred times. The life of the flesh is in the blood. I always received it as theology: a truth about atonement, about sacrifice. I filed it under faith.

It was not until I sat with my CT angiogram in my hands that I understood what it is also saying at the biological level. The life of every organ, every cell, every tissue depends entirely on the blood reaching it. When the blood stops reaching the flesh, the flesh dies.

I had always thought about what was inside the blood: the red cells carrying oxygen, the white cells mounting immunity, the platelets sealing breaches, the hormones and nutrients riding the current. I thought of blood as both the delivery truck and the garbage truck. What I never thought about was the vessel itself.

The endothelial cell is the single layer of cells lining every blood vessel in the body. One cell thick. Covering more than 7,000 square meters of surface area in an adult. Not passive. Not the walls of the pipes. An active endocrine organ that produces nitric oxide, the master vasodilator and endothelial protector, that senses shear stress from blood flow and responds by remodeling the vessel wall.

When the endothelium is injured, everything downstream of it fails. Heart disease is endothelial disease. Stroke is endothelial disease. Aortic aneurysm, pulmonary embolism, deep vein thrombosis, cerebral aneurysm, and very likely wet macular degeneration: all begin, at the biological root, with an endothelium damaged beyond its capacity to repair.

The specific mechanism: the amino acid L-arginine, drawn from food, enters the endothelial cell and binds to eNOS, endothelial nitric oxide synthase. eNOS converts arginine to nitric oxide. Nitric oxide dilates the vessels, prevents platelet adhesion, inhibits inflammation, and keeps the arterial surface clean.

There is a molecule called ADMA. Asymmetric Dimethylarginine. It is produced in every cell as a byproduct of normal protein metabolism. ADMA is structurally almost identical to arginine. The only difference is two methyl groups added to the same nitrogen atom on the guanidino end. That difference is invisible to eNOS. The enzyme cannot distinguish arginine from ADMA until it is already bound. When ADMA occupies the eNOS active site, nothing is produced. No nitric oxide. The factory is running. Nothing comes out.

The rescue enzyme is DDAH, dimethylarginine dimethylaminohydrolase. DDAH breaks down ADMA into citrulline and dimethylamine, clearing more than 80% of circulating ADMA. A meta-analysis of 22 prospective studies found that individuals in the top third of ADMA values had a 42% higher risk of cardiovascular events, 39% higher risk of coronary heart disease, and 60% higher risk of stroke.

What destroys DDAH: the Western diet. 

• Oxidized LDL directly inactivates DDAH and elevates ADMA simultaneously, a spiralling feedback loop. 

• High homocysteine down-regulates DDAH production at the genetic level. 

• Smoking, hyperglycemia, hypertension, and chronic inflammation all independently inactivate DDAH through oxidative mechanisms.

The dietary countermeasure operates on both sides. 

• Plant foods stock the substrate: 

  • Pumpkin seeds at 5,200 mg of arginine per 100g, 

  • Soybeans at 2,300 mg, 

  • Lentils at 1,900 mg, 

  • Chickpeas at 1,300 mg, 

  • Black beans at 1,000 mg. 

• On the other side, polyphenol antioxidants protect DDAH from oxidative destruction: 

  • Green tea EGCG, 

  • Pomegranate punicalagins, and 

  • Omega-3 fatty acids. 

Every element of the Reversal protocol targets this pathway as well.

When I saw this diagram in a study, I thought, “Eureka!” Blood-retinal barrier injury and neovascularization. That was my wet macular degeneration! And on the other side, heart. Same mechanism. Endothelial dysfunction. Increased ADMA. 

Now I am sure I can heal my Wet AMD along with my heart disease. And not only I, but everyone who follows me.

The Question for Everyone

This is not only my question. The anatomy does not discriminate. If you are reading this, you almost certainly have this disease in some stage, in some arterial territory, accumulating silently. The question is not whether it has started. The question is which stage, which vessels, and whether the biological machinery of reversal can be activated before the disease reaches the threshold at which it announces itself.

The protocol I am running is not a personal experiment but a proof of concept. If it works in my arteries and the carotid data show it is working, then it works through mechanisms universal to human biology. The endothelium that repaired in my carotid territory responds to the same signals as the endothelium in your coronary arteries, your cerebral vessels, and your retinal circulation.

My father is still here. Thank you, God. My CT angiograms are scheduled every six months, and my target for reversal is June 2028. That is the reckoning.

Water erodes rock. The river does not stop.

Your Questions

Questions worth sitting with:

For yourself. For someone you love. Answer them in the quietness of your day.

1.  When did you last have imaging of your arteries, not just blood tests?

A lipid panel tells you risk factors. A CAC score or CT angiogram tells you what has already built up in the vessel wall. These are not the same question. Call your physician tomorrow and ask for a coronary artery calcium scan.

2.  What did you eat yesterday, and what was that food doing to your nitric oxide production?

Every meal either elevates ADMA and silences eNOS, or it provides the arginine and polyphenols that protect DDAH and keep your endothelium producing the signal that keeps your arteries open. There is no neutral meal.

3.  Who in your life has this disease right now and does not know it?

You thought of someone while reading this. Forward this to them. Ten seconds. It may matter more than either of you knows.

MORE READINGS YOU’LL ENJOY

Health

• Reversing My 77% Heart Plaques

• Stats Say You Likely Have Heart Plaque

• The Healing Power of Food: Nitric Oxide

Wealth

• The Cocoon of Wealth

• The Power of the Compound Effect

• Relentless Iteration to Mastery

Meaning

• The Courage to Your Magnum Opus

• Leave Your Mark in This World

• The Architecture of Your Life

I pray you unlock your heart to reach the height of your full potential
by discovering your calling.

Kevin Ham, MD

APPENDIX

https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1183586/full

Elevated ADMA, an endogenous inhibitor of nitric oxide synthase, drives the onset and progression of diabetic microvascular complications including retinopathy, nephropathy, neuropathy, and cardiomyopathy through endothelial dysfunction, oxidative stress, inflammation, and fibrosis.

https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2012.00132/full

Examines how vascular aging impairs endothelial function primarily through reduced nitric oxide bioavailability, identifying ADMA accumulation, oxidative stress, enhanced vasoconstrictor activity, and low-grade inflammation as the key mechanisms driving age-related cardiovascular dysfunction.

https://eaglebio.com/eaglebio-biomarker-spotlight-adma/

ADMA is an endogenous molecule detectable in human blood and urine that is structurally homologous to L-arginine and acts as an inhibitor of nitric oxide synthesis,positioning it as a clinically measurable biomarker of endothelial dysfunction and cardiovascular risk.