The Hidden Cause of Heart Disease: Inflammation vs. Cholesterol

For most of my career, the cholesterol panel was the heart-health conversation. LDL high? Statin. LDL fine? You’re good to go. But I kept seeing people with “perfect” cholesterol who were anything but healthy, and people with higher LDL who never developed disease. I saw a version of this firsthand as the primary author of a vitamin D trial in people with heart failure, which I’ll share below.

The research has now caught up with what many of us in functional nutrition suspected. In September 2025, the American College of Cardiology formally called inflammation a driver of heart disease that is compelling and ready to act on, and recommended screening for it alongside cholesterol. So which one should you actually worry about more? Here is what the evidence says, in plain language.

Here’s the problem: the public hasn’t caught on yet. Most people still walk out of their annual physical knowing their cholesterol numbers and nothing about their inflammation. Headlines, food packaging, and even many routine checkups are still built around the old cholesterol-only story. After 25 years in clinical nutrition and my own work in cardiovascular research, I’m here to change that, and this post is where I’m starting.

Cholesterol Is the Fuel, Inflammation Is the Spark

Atherosclerosis starts when LDL and other apoB-containing particles slip into the artery wall and get trapped. That part is well established: genetic studies, drug trials, and decades of population data all show that more LDL exposure over a lifetime means more plaque. This is why the 2026 ACC/AHA guideline pushes for lowering LDL earlier in life.

But trapped cholesterol alone does not cause a heart attack. The immune system treats oxidized cholesterol in the artery wall as a threat. Macrophages swallow it, become foam cells, and release inflammatory signals like IL-1β and IL-6. That smoldering inflammation enlarges the plaque, thins its protective cap, and eventually can crack it open. A cracked plaque triggers a clot, and the clot is what blocks blood flow.

This is why framing it as “inflammation vs. cholesterol” is a little misleading. They are partners. Still, the question of which one predicts trouble better has a surprisingly interesting answer.

What the Research Says About Which Predicts Risk Better

Two landmark analyses from Dr. Paul Ridker’s group at Brigham and Women’s Hospital shifted the conversation.

The 30-year Women’s Health Study (NEJM, 2024). Researchers measured hs-CRP, LDL cholesterol, and lipoprotein(a) once in nearly 28,000 healthy women (average age 55) and followed them for three decades. Women in the highest fifth of hs-CRP had about a 70% higher risk of a major cardiovascular event than those in the lowest fifth. For LDL, the increase was 36%. For Lp(a), 33%. All three added independent information, and women high in all three had the greatest risk.

People already on statins (The Lancet, 2023). A pooled analysis of more than 31,000 statin-treated patients from three major trials compared “residual inflammatory risk” with “residual cholesterol risk.” High hs-CRP was a stronger predictor of future heart attacks, strokes, cardiovascular death, and death from any cause than LDL. In this group, the leftover LDL barely moved the needle, while inflammation more than doubled the risk of dying from cardiovascular disease.

That second finding is the one I want you to sit with. Once cholesterol is brought down, inflammation is often the biggest risk that remains, and most people have never had it measured.

Statins help, but they only partially fix inflammation. They do lower hs-CRP somewhat, and that’s part of why they work. In the JUPITER trial, rosuvastatin lowered LDL by about 50% but hs-CRP by only about 37%. Statins don’t address what’s actually fueling the fire: excess visceral fat, blood sugar swings, a leaky gut, chronic stress, poor sleep, ultra-processed food, or daily exposure to foods your immune system reacts to. That’s why so many people on statins, with LDL numbers their doctors are happy with, still carry elevated inflammation and the heart risk that comes with it. Cardiologists call this “residual inflammatory risk,” and it’s exactly the gap that nutrition and lifestyle are best positioned to close.

Where I Stand on Statins

I’ll be honest: I’m not a fan of statins as the automatic, one-size-fits-all answer. They lower LDL, but they only partially address inflammation, many people struggle with side effects like muscle aches, and they do nothing for the upstream drivers of disease. When someone truly needs their LDL lowered, I think there are better tools to consider.

Repatha (evolocumab). This injectable PCSK9 inhibitor lowers LDL far more powerfully than most statins, often by 50 to 70%. It now has strong outcome data behind it, too. In the VESALIUS-CV trial of more than 12,000 high-risk adults who had never had a heart attack or stroke, adding evolocumab cut the risk of a first heart attack, stroke, or coronary death by 25% and heart attacks alone by 36%. A 2026 follow-up analysis found a 20% reduction in death from any cause. One important detail: in these trials, Repatha was added on top of the highest statin dose people could tolerate, so they show the benefit of lowering LDL further, not of replacing statins outright.

Berberine. This plant compound works through the same basic pathway as Repatha, reducing PCSK9 so the liver clears more LDL from the blood. The LDL drop is more modest, roughly in the range of a low-dose statin, but berberine does things statins don’t. It improves blood sugar and insulin resistance, lowers triglycerides, supports a healthier gut microbiome and gut barrier, and calms inflammatory signals like TNF-alpha and IL-6. In other words, it works on several branches of the inflammation umbrella at once. I’ve even convinced cardiologists I used to work with to take it themselves. I cover the research in depth in my post on berberine for gut, heart, and brain health.

A few cautions matter here. Berberine hasn’t yet been tested in large trials measuring heart attacks and deaths the way statins and Repatha have, and the 2026 cholesterol guideline doesn’t endorse supplements for lowering LDL. Berberine also affects liver enzymes that process many drugs, including some statins and blood thinners. If you’re on a statin or any heart medication, please don’t stop or swap anything on your own. Bring these options to your prescriber and decide together.

So Why Hasn’t Cholesterol Lost Its Crown?

To be fair to cholesterol, there are real reasons it stays central:

• LDL is proven to be causal. Genetic studies show that people born with lower LDL have fewer heart attacks, and nearly every drug that lowers LDL lowers events. CRP itself does not appear to be causal. It is a messenger, a smoke detector for the upstream IL-1β and IL-6 pathway that genuinely does drive disease.
• Lower LDL works. Statins, ezetimibe, and PCSK9 inhibitors have decades of outcome data behind them.
• Anti-inflammatory drugs are newer and mixed. The CANTOS trial proved in 2017 that blocking IL-1β reduced heart attacks without touching cholesterol, and low-dose colchicine is now FDA-approved for stable heart disease. But a large 2025 trial of colchicine right after a heart attack (CLEAR SYNERGY) did not show benefit, so this area is still maturing.

Even the experts don’t fully agree on testing yet. The 2025 ACC scientific statement calls for near-universal hs-CRP screening. The 2026 ACC/AHA dyslipidemia guideline, published six months later, still uses hs-CRP more selectively, as a “risk enhancer” to refine decisions when someone’s calculated risk is borderline or uncertain, while recommending that every adult get Lp(a) measured once.

Inflammation Is a Much Bigger Umbrella Than LDL

Here is where the “bigger risk for health” question really tips toward inflammation. High LDL is primarily a cardiovascular problem. Chronic low-grade inflammation is a common thread running through most of the chronic diseases that shorten and diminish lives. A 2019 review in Nature Medicine estimated that more than half of all deaths worldwide are attributable to inflammation-related diseases, including heart disease, stroke, cancer, diabetes, chronic kidney disease, fatty liver disease, and autoimmune and neurodegenerative conditions.

Autoimmune disease. In autoimmune conditions like rheumatoid arthritis, lupus, psoriasis, Hashimoto’s, and inflammatory bowel disease, the immune system turns inflammation against the body’s own tissues. Anything that adds to the background inflammatory load, like a poor diet, a leaky gut barrier, chronic stress, or poor sleep, tends to fuel flares. The connection runs both ways, too: autoimmune disease dramatically raises heart risk, which I’ll come back to below.

Dementia and cognitive decline. Inflammation doesn’t stay out of the brain. In a large U.S. study published in Neurology, people with higher inflammatory markers in midlife had steeper cognitive decline over the next 20 years. Inflammatory signals like IL-6 activate the brain’s immune cells (microglia), and chronic activation is implicated in the damage seen in Alzheimer’s disease. To be fair to cholesterol, the 2024 Lancet Commission on dementia did add high LDL to its list of modifiable risk factors. But inflammation touches the brain through far more pathways.

Type 2 diabetes and insulin resistance. This is one of the clearest links on the list. Inflammatory cytokines like TNF-alpha and IL-6 interfere directly with insulin signaling, so cells stop responding to insulin the way they should and blood sugar climbs. In the same Women’s Health Study cohort discussed above, women with the highest CRP levels had about four times the risk of developing type 2 diabetes over four years compared with women with the lowest levels, even after accounting for weight, family history, smoking, and exercise. A leaky gut adds fuel: when bacterial fragments called lipopolysaccharides (LPS) cross a damaged gut barrier, they trigger inflammation and insulin resistance, a process researchers call metabolic endotoxemia. And insulin resistance feeds back into heart disease, raising triglycerides and the number of plaque-forming particles. Inflammation, blood sugar, and cholesterol are all part of the same loop.

Depression, fatty liver, and cancer. Roughly a quarter of people with depression have elevated CRP, and this “inflammatory depression” often responds poorly to standard antidepressants. Chronic inflammation also drives fatty liver disease and creates an environment that favors some cancers. In the CANTOS trial, lowering inflammation unexpectedly reduced lung cancer rates as well as heart attacks.

Lowering LDL with a medication can protect your arteries, and that’s valuable. But it won’t touch most of the conditions on that list. Lowering inflammation can.

Autoimmune Disease and Diabetes Multiply Heart Risk

If you want to see how much inflammation matters for the heart, look at what happens to people living with inflammatory diseases. The numbers are staggering.

Diabetes doubles the risk. In a landmark analysis of nearly 700,000 people across 102 studies, having diabetes meant about twice the risk of coronary heart disease and 2.27 times the risk of an ischemic stroke, independent of age, smoking, blood pressure, and weight. Here’s the part that matters most for this post: that risk barely budged when researchers also accounted for cholesterol. Diabetes raises heart risk through pathways a lipid panel doesn’t capture, including high blood sugar damaging blood vessel walls, insulin resistance, and chronic inflammation. The extra risk was even greater in women and in people in their 40s and 50s, and the researchers estimated that diabetes accounts for roughly 1 in 10 cardiovascular deaths in developed countries.

Autoimmune disease raises it just as much, and sometimes more. The 2022 Lancet study drew on health records for 22 million people in the UK, comparing about 446,000 people with autoimmune disease to more than 2 million matched people without it. Over roughly six years, 15.3% of the autoimmune group developed cardiovascular disease compared with 11% of the comparison group. Every one of the 19 autoimmune diseases studied raised heart risk, which led the researchers to conclude that autoimmunity itself, not any single condition, is the risk factor. The findings are hard to ignore:

• Systemic sclerosis raised cardiovascular risk about 3.6 times, Addison’s disease and lupus about 2.8 times, and type 1 diabetes about 2.4 times.
• Risk climbed with each additional autoimmune condition. People with three or more had nearly 3.8 times the risk.
• Younger people were hit hardest. Those diagnosed with autoimmune disease before age 45 had 2.3 times the risk of their peers.
• The extra risk showed up across every type of cardiovascular disease studied and held after accounting for traditional risk factors like blood pressure, cholesterol, and smoking.

The study’s authors pointed out that this excess risk is on par with type 2 diabetes. Yet while people with diabetes get targeted heart screening and prevention, people with autoimmune disease usually don’t. If you’re a woman in your 30s with lupus or Hashimoto’s and “normal” cholesterol, a standard heart checkup may tell you you’re low risk when you’re not. That’s exactly the blind spot a cholesterol-only approach creates, and it’s why the 2026 guideline now lists chronic inflammatory disease as a heart-risk enhancer.

If you live with an autoimmune condition, diabetes, or prediabetes, ask for hs-CRP alongside your lipid panel, and treat calming inflammation as heart protection, not just symptom relief.

How Processed Foods Fuel the Fire

If inflammation is the umbrella, ultra-processed food is one of the biggest things feeding it. Ultra-processed foods are industrial products built from refined starches, sugars, oils, and additives: soda, packaged snacks, processed meats, sweetened cereals, frozen meals, and most fast food. They now make up well over half of the calories Americans eat.

The research linking them to inflammation keeps growing. In a 2025 study of more than 9,000 U.S. adults in The American Journal of Medicine, people who got the most calories from ultra-processed foods were significantly more likely to have elevated hs-CRP, even after accounting for age, smoking, activity, and other health factors. A 2025 scoping review of 24 human studies found that most analyses in adults showed higher CRP with greater ultra-processed food intake. And a 2024 umbrella review in the BMJ, covering nearly 10 million people, linked ultra-processed foods to 32 health outcomes, with the strongest evidence for cardiovascular death, type 2 diabetes, and common mental health disorders. Notice how closely that list matches the inflammation umbrella above.

Here’s how processed foods drive inflammation:

• They damage the gut barrier. Common emulsifiers like carboxymethylcellulose and polysorbate 80 thin the protective mucus layer in the gut and shift the microbiome toward inflammatory species. In a controlled human feeding study, carboxymethylcellulose alone reduced beneficial gut bacteria and their protective metabolites. When the gut barrier weakens, bacterial fragments leak into circulation and keep the immune system on alert.
• They spike blood sugar. Refined starches and added sugars cause rapid glucose and insulin surges that generate oxidative stress and inflammatory signaling, and over time they promote visceral fat, which pumps out IL-6.
• They starve your microbiome. Processed foods are nearly fiber-free. Without fiber, gut bacteria can’t produce short-chain fatty acids like butyrate, one of the body’s natural anti-inflammatory signals.
• They’re easy to overeat. In a tightly controlled NIH study, people ate about 500 more calories a day on an ultra-processed diet than on a minimally processed one, even though the meals were matched for sugar, fat, fiber, and sodium.
• They carry hidden reactive ingredients. Corn and soy derivatives are in a huge share of packaged foods as syrups, starches, oils, lecithin, and fillers. For the many clients who react to them on MRT, processed foods mean constant, unseen exposure.
• They’re linked to autoimmune gut disease. In a study of more than 116,000 adults across 21 countries, people eating five or more servings of ultra-processed food a day had a significantly higher risk of developing inflammatory bowel disease.

The encouraging flip side is that the single most powerful anti-inflammatory move most people can make is also the simplest: eat more foods that don’t come with an ingredient list. Growing up on a farm and ranch made me a scratch cook, and I’ve come to believe it’s possibly the single most important thing you can do for your health: eat foods you recognize as food, not food in shiny, sterile wrappers with brand names.

Notice what isn’t on the list of proven offenders: whole animal foods. In a February 2026 clinician’s guide from the American College of Cardiology’s nutrition work group, ultra-processed foods landed in the “evidence of harm” category, while whole, unprocessed red meat and moderate dairy did not. And a 2025 meta-analysis found red meat raised CRP mainly in people who already had cardiometabolic disease, ate processed forms, and ate it daily or more, not as a blanket effect. The industrial processing is the bigger problem. I break down that research, including who funded it, in assessing the myths of animal-based foods and inflammation.

Refined wheat deserves a special mention because it’s the backbone of so many processed foods. Gluten raises zonulin, a protein that loosens the tight junctions of the gut lining, and in a large Dutch population study zonulin was one of the leaky-gut markers most strongly tied to BMI, blood sugar, and CRP. A separate wheat protein family called ATIs activates the innate immune system directly, independent of gluten. A 2025 meta-analysis in Gut found roughly 1 in 10 people worldwide report gluten or wheat sensitivity, and on MRT testing I see it far more often than that, including in my own results after a decade of suspecting it. I cover the full gluten-inflammation-weight cycle in can gluten intolerance cause weight gain?

The Labs I Want You to Know

This is where my “test, not guess” philosophy comes in. A standard lipid panel is only one piece.

You can order a functional panel including hs-CRP and advanced lipids through my Labs page.

How MRT Measures Your Inflammatory Response to Foods

hs-CRP tells you that inflammation is present. It doesn’t tell you where it’s coming from. For many of my clients, and for me personally, a big piece of that answer turned out to be food.

Most people know about food allergies, which are driven by IgE antibodies and cause fast, obvious reactions like hives or swelling. Food sensitivities are different. They are delayed, dose-dependent, and often show up as symptoms you’d never connect to lunch: joint pain, headaches, bloating, brain fog, skin flares, fatigue, or congestion. And because they’re delayed, they are very hard to pin down with guesswork or elimination diets alone.

The Mediator Release Test (MRT) looks at this directly. A blood sample is exposed to 170 individual foods and food chemicals. When white blood cells react to a food, they release inflammatory mediators such as histamine, cytokines, prostaglandins, and leukotrienes, and in doing so they shrink. MRT measures that change in the cells, which gives a readout of how strongly your immune system reacts to each food. Foods are then sorted into low-, moderate-, and high-reactive categories.

The results guide the LEAP (Lifestyle Eating and Performance) protocol. Rather than cutting out dozens of foods at once, you start with your least reactive foods and systematically add others back while tracking symptoms. The goal is to lower the daily inflammatory load your immune system is dealing with, then expand your diet as far as your body allows.

This matters for the inflammation-vs.-cholesterol question because a food you react to isn’t a one-time event. If you eat it every day, your immune system is being provoked every day. That steady, low-grade stimulation is exactly the kind of chronic inflammation that the heart research is pointing to.

My own results are a good example of why guessing fails. Sunflower seeds, mustard, olive oil, cow’s milk, wheat, soybean, and lentils all came back reactive for me, and most of them are foods any “anti-inflammatory diet” would tell you to eat more of. Within 10 days of removing them, my vestibular migraines, post-nasal drip, joint aches, and chronic skin itching faded. I explain why generic anti-inflammatory diets are educated guesswork for the individual in how inflammation causes weight gain.

What MRT and LEAP Have Done for Me and My Clients

I didn’t come to MRT as a skeptic turned believer. I came to it as a patient. My own protocol led to a 96% reduction in my symptoms, and seasonal allergies I’d had for years resolved. I shared the full story in how MRT testing transformed my health from the inside out.

As a Certified LEAP Therapist, I’ve since run many clients through MRT, and the patterns surprise people. Corn shows up as reactive in roughly half of my clients, and soy in about 60%. Both are hidden in thousands of packaged foods, oils, and fillers, which is why so many people never figure it out on their own. When clients remove their reactive foods and follow LEAP, I routinely see dramatic drops in the symptoms that signal inflammation: joint pain easing, digestion settling, headaches fading, skin calming, and energy returning.

One client, eight weeks into her LEAP protocol, put it better than I can: “The binge eating stopped. I’m not white-knuckling past the kitchen at 9pm anymore. I thought I had a willpower problem. I had an inflammation problem.” That’s the cortisol and blood sugar side of inflammation settling down, and it’s the same inflammation that the heart research is pointing to.

To be transparent, the published research on MRT is still relatively small, and most of it has focused on conditions like IBS and migraine. That’s one reason I encourage pairing MRT with hs-CRP. Check your hs-CRP before you start LEAP and again a few months in. That turns “I feel better” into a number you can track, which is what “test, not guess” is all about.

MRT is not a self-checkout test on my site. I order it through a consultation so we can interpret your results together and build your LEAP plan. Learn more in my complete guide to MRT and the LEAP method, or reach out to book a consult.

How to Lower Inflammation and Cholesterol at the Same Time

The good news is that most of the best tools work on both.

• Cut back on ultra-processed foods. Swap packaged snacks, soda, processed meats, and convenience meals for whole foods you prepare yourself. Reading labels for emulsifiers, added sugars, and hidden corn and soy is a good start.
• Personalize your anti-inflammatory diet. Mediterranean-style eating has strong population research behind it. In the PREDIMED trial, a Mediterranean diet rich in extra-virgin olive oil or nuts cut major cardiovascular events by roughly 30%. But a population average can’t tell you how your body responds. I’m a good example: legumes, fish, and olive oil, three pillars of the Mediterranean diet, all inflame my body. A food is only anti-inflammatory if your immune system agrees. Use whole, minimally processed foods as your starting point, then personalize with tools like MRT testing, symptom tracking, hs-CRP, and even a glucose monitor, as I describe in my CGM post.
• Get fiber from plants you tolerate. Soluble fiber lowers LDL, and fermentable fibers feed gut bacteria that produce anti-inflammatory short-chain fatty acids. Oats, flax, vegetables, berries, and beans are all good sources if they agree with you. Choose the ones your body handles well.
• Find omega-3s that work for you. Omega-3s help resolve inflammation and lower triglycerides. Fatty fish like salmon and sardines are the richest source, but if fish doesn’t agree with you, algae-based omega-3s, walnuts, chia, and flax are alternatives, and an omega-3 index test can tell you whether you’re getting enough.
• Address visceral fat and blood sugar. Belly fat is metabolically active tissue that pumps out IL-6, and inflammation in turn drives weight gain. In the SUN cohort, which followed 7,027 normal-weight adults for about 8 years, those eating the most pro-inflammatory diets had a 32% higher risk of becoming overweight or obese. Chronic inflammation also keeps cortisol elevated, which pushes fat storage toward the belly, a loop I unpack in how inflammation causes weight gain. Even modest weight loss lowers hs-CRP.
• Move daily. Regular exercise lowers CRP independent of weight loss.
• Protect your sleep and manage stress. Short sleep and chronic stress both raise inflammatory markers. I dig into the cortisol side of this in Cortisol Fix, and adaptogens like those in my ashwagandha for cortisol guide may help some people.
• Remove hidden inflammatory triggers. Gum disease, gut barrier problems, and daily exposure to reactive foods can all keep inflammation simmering. MRT and LEAP, described above, are my go-to tools for finding the food piece.
• Consider targeted polyphenols. Compounds like quercetin and resveratrol have anti-inflammatory effects in research, though they aren’t a replacement for proven therapies. Notably, the 2026 guideline advises against relying on supplements to lower cholesterol.

If your LDL or Lp(a) is high, your family history is strong, or your hs-CRP stays elevated despite lifestyle changes, please work with your physician. Medication is sometimes exactly the right tool, and nutrition makes it work better.

Heart Health Is Never Just One Number: What My Vitamin D Study Found

If there’s one thing 25 years in clinical practice has taught me, it’s that no single lab value tells the whole story, not LDL, and not hs-CRP either. Heart health is shaped by inflammation, blood sugar, hormones, nutrient status, stress, and how well the heart muscle itself is working. My own research is a good example.

Stress is a perfect example of a risk factor that never shows up on a cholesterol panel. In the landmark INTERHEART study of nearly 25,000 people across 52 countries, psychosocial stress raised the odds of a first heart attack 2.67 times, more than diabetes (2.37) or high blood pressure (1.91). Chronic stress drives sustained cortisol release, which feeds the same inflammatory cascade that damages arteries. The same study found that the ratio of ApoB to ApoA1 was the single strongest predictor of heart attack risk, yet fewer than 1% of insured Americans get ApoB tested in a given year. I dig into both findings in assessing the myths of animal-based foods and inflammation.

At Providence St. Patrick Hospital and the International Heart Institute of Montana here in Missoula, my colleagues and I conducted a six-month randomized, double-blind, placebo-controlled trial of vitamin D3 in 40 people with stable heart failure who were low in vitamin D. Half took 10,000 IU of vitamin D3 daily and half took a placebo. We published the results in BMC Cardiovascular Disorders in 2017.

It’s important to understand who was in this study. These weren’t healthy people trying to prevent heart disease. Every participant already had established heart disease, diagnosed heart failure serious enough to limit their daily activity, and was being treated by cardiologists in a specialty heart failure clinic. Most nutrition research on heart health focuses on prevention in healthy people, and far less asks whether nutrition can still help once disease has set in. Our results suggest it can. Even with established disease and full medical therapy on board, correcting a deficiency changed how people felt and how their hearts were responding. It’s never too late for nutrition to matter.

Here’s what we found:

• These patients were already on “everything.” Every participant was on stable, guideline-directed heart failure medications, and they were also taking statins as indicated. In other words, their cholesterol was being managed. Vitamin D still made a measurable difference, which is exactly the point of this post.
• People felt significantly better. Quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire, a validated heart failure tool, improved meaningfully in the vitamin D group and declined in the placebo group. Physical function, overall quality of life, and symptom burden all improved. For people living with heart failure, how they feel day to day is not a soft outcome. Better quality-of-life scores predict fewer hospitalizations and longer survival.
• A key heart-strain marker held steady. BNP, a hormone released when the heart is under stress and one of the strongest predictors of outcomes in heart failure, stayed nearly flat with vitamin D but rose substantially with placebo.
• Inflammation came down in men. hs-CRP dropped by about 2 mg/L in men taking vitamin D compared with placebo, though it didn’t change in women. We also found that parathyroid hormone, which is linked to inflammation and to worse heart failure outcomes, improved even more strongly with vitamin D in patients whose hs-CRP was elevated.
• Vitamin D levels rose safely. Blood levels climbed from about 20 ng/mL to an average of 70 ng/mL, calcium stayed completely normal, and no one needed a dose reduction.

To put the quality-of-life result in perspective: the clinical summary score improved by an average of 8 points with vitamin D. In our paper, we noted that this compared favorably with the changes reported in a landmark heart failure drug trial. That’s a comparison across very different studies, so it needs confirming in larger trials, but the implications could be large if it holds up.

Why would one vitamin affect so many things at once? Because vitamin D isn’t really a vitamin in the usual sense. Its active form, calcitriol, works like a hormone. Heart muscle cells, blood vessel cells, and immune cells all carry vitamin D receptors, and those receptors bind to nearly 2,800 sites across the human genome. In one randomized trial we cite, correcting vitamin D deficiency changed the expression of 291 genes in white blood cells, including genes tied to oxidative stress and blood vessel health. Vitamin D also calms inflammation directly by dialing down the NF-κB pathway and reducing inflammatory cytokines like IL-6 and TNF-alpha, the same messengers that drive plaque, insulin resistance, and the other conditions under the inflammation umbrella. When someone is deficient, a lot of systems are running below par at the same time.

I want to be clear about what our study does and doesn’t show. It was a small trial, everyone in it was low in vitamin D, and the results apply to people with existing heart failure, not necessarily to healthy people. Large trials giving vitamin D to the general population, such as VITAL, haven’t shown fewer heart attacks, likely because most participants weren’t low to begin with. Interestingly, VITAL did find a 22% reduction in new autoimmune diseases, another reminder of how closely vitamin D is tied to immune health. The takeaway isn’t “everyone should take high-dose vitamin D.” It’s “know your level, and correct a deficiency.” A 25-hydroxyvitamin D test is available on my Labs page, and anyone with heart disease should work with their cardiology team before starting high-dose supplements.

And that’s really the theme of this whole post. You can’t fully judge heart health, or whole-body health, from one number on a lab report.

My Take: Which Is the Bigger Risk?

If you forced me to choose, here is how I would put it. LDL contributes to plaque, so it still matters for your arteries. But plenty of people with low LDL go on to have heart attacks, and a cholesterol number alone can’t tell you who they are. For predicting who actually has a heart attack, inflammation is at least as important and often more so. And for your health as a whole, it isn’t close. Chronic inflammation sits upstream of autoimmune disease, dementia, diabetes, depression, fatty liver, and more, and much of it is being fed by what’s on our plates.

The better question isn’t “which one?” It’s “have I checked both?” Ask for hs-CRP the next time your cholesterol is drawn, get Lp(a) tested once, and treat inflammation as a signal worth tracking down.

The science has moved. Now it’s time for the conversation in exam rooms and kitchens to move with it. If this post changed how you think about your heart, share it with someone who is still watching only their cholesterol.

Frequently Asked Questions

References

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