The Oldest Woman (117) Had “High” Cholesterol 🩸— Here’s What That Really Means🤔(Link 🔗 in 8/8)
1/8) The world’s oldest woman just died. Before she passed, she pleaded, “Please study me.”
A new paper in Cell Reports Medicine (PMID: 39322234) just published provides a deep dive into her genes, metabolism and microbiome. What made this 117-year-old such a supercentenarian?
As a metabolism scientist, this is the kind of data I’d die for (figuratively speaking). Stick with me. I’ll break down what her biology really tells us about aging, and why we might be obsessed with the wrong biomarkers.
2/8) When I first read the paper, I noticed something odd.
The authors detailed her lipid profile (HDL, VLDL-TG, etc.) but her LDL-C and ApoB—the numbers most doctors obsess over—was nowhere in the main text.
I had to go hunting in the supplementary data. There it was, buried in a single line of Supplemental Figure 8B: elevated, and in the “red.” -- Granted, it wasn’t super high… but it wasn’t low either.
So what gives? Why was it not mentioned in the main text. I provide thoughts (not conspiracy theories) in the letter. But now I know I have your attention…
cc @realDaveFeldman @AdrianSotoMota
3/8) Now for the next “paradox” - her telomeres 🧬😲
Telomeres are the protective caps on our chromosomes. Think of them like the plastic tips on a shoelace. The prevailing wisdom is that as they shorten with age, our health declines.
You’d expect a 117-year-old to have either freakishly long telomeres or be riddled with disease. Maria Morera had neither.
Her telomeres were tiny!!! I was expecting Godzilla telomeres and was met with chihuahuas exactly as short as you'd predict for her chronological age.
Yet, she was remarkably healthy. This is a crucial finding: telomere length may simply be a clock, not a direct measure of your healthspan.
cc @bryan_johnson, of interest?
4/8) So if it wasn't long telomeres, what set her apart?
Her mitochondria. As every high schooler knows, these are the “powerhouses in our cells,” and their decline is a key hallmark of aging.
Maria’s, however, were functioning like those of someone decades younger. The paper notes her mitochondria showed "not only preserved but also robust mitochondrial function."
cc @ChrisPalmerMD @MitoPsychoBio
5/8) The evidence for her low "inflammaging" status is compelling. Beyond her genetics, her bloodwork showed remarkably low levels of GlycA and GlycB—advanced biomarkers of systemic inflammation. 🔥
Summary so far: Genetics gave her an edge → leading to highly efficient mitochondria and a low inflammatory burden → which created a biological environment where factors like high LDL or short telomeres didn't lead to disease.
6/8) So, what about her lifestyle? For the last 20 years of her life, she ate a consistent diet that included a conspicuous amount of yogurt—three servings per day.
And the paper even specified the bacterial strains: Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus. She was also a heavy user of egg protein and olive oil.
I feel almost as if I designed her diet!
P.S. Smoked Maldon Salt Greek Yogurt is a 12/10
7/8) The clinical implications here are profound. Her case suggests that a state of low inflammation, a “highly engaged lipid metabolism,” and good mitochondrial health can grant resilience against factors we typically view as "bad." Yes, she was genetically gifted. But we can still turn her insights into action… What do we do with this knowledge?
8/8) In the rest of the letter (linked below), we turn these insights into action.
While you can't change your genes, you can support your mitochondria.
I break down her full meal plan, the specific U.S. yogurt brands I found that contain those exact bacterial strains, and actionable strategies — from fasting protocols to light exposure — that support the same mitochondrial resilience seen in this remarkable supercentenarian.
As a Neuroscientist, this Graph changed how I think about Dementia Risk Factors
1/5) Microplastics are accumulating in the human brain at an alarming rate. Over the past ~8 years, brain microplastics have increased by ~50%.
But that’s not the worst part…
Consistently, microplastic levels in the brain are much higher in people with dementia (purple) than in those without dementia.
The association is so massive the graphs needs a Y-axis break!
2/5) The researchers behind this work hypothesize that the exponentially increasing concentrations of micro- and nanoplastics in the environment are driving a parallel increase in plastic accumulation in the human brain.
True—correlation ≠ causation. But you cannot do randomized controlled trials here. It’s neither ethical nor feasible.
And when an association is this large—and reverse causality is unlikely—it demands serious attention.
3/5) Mechanistically, this makes sense. Microplastics can drive oxidative stress, chronic neuroinflammation, and vascular injury—three core pillars underlying dementia.
Cholesterol Debates in the Era of Medical Mistrust
1/4) This graph shows the hazard ratio for coronary heart disease associated with insulin resistance score (LP-IR) versus LDL cholesterol.
It’s not even close. Insulin resistance dwarfs LDL—with a >14-fold difference in relative risk.
2/4) So why does LDL get all the attention?
Simple: It’s easy to manipulate—and highly profitable.
The statin industry alone generates over $20 billion annually. It would be naive to pretend financial interests don’t shape medical priorities.
That’s not a conspiracy theory. It’s acknowledgement of incentive structures that ultimately dictate the spotlight of research, guidelines and medicine.
3/4) And—despite better drugs and relentless focus on LDL as the biomarker cardiology loves to hate—CVD remains a top killer.
That shouldn't be acceptable. Big problems demand hard conversations—and honest autopsies on where we’ve gone wrong in medicine.
If we’re serious about orphaning cardiovascular disease, we must target the metabolic dysfunctions beneath the surface—the ones that often get overlooked and left in the shadows.
Protein-Maxing and the Illusion of Nutritional Progress
1/8) David Bar is the world’s most hyped protein bar—boasting ~75% of Calories From Protein (CFP) and the tagline “only what’s necessary.”
But how does it stack up? Let's have a dispassionate discussion...🧵👇 (link in 8/8)
2/8) Formulation: I’d give it a 3/10.
Despite the “only what’s necessary” claim, it contains two artificial sweeteners (Ace-K and sucralose) and the controversial artificial fat EPG.
Seems like inconsistent messaging at the very least. But what about these ingredients?
3/8) Take, sucralose, for example.... It has been shown in human-controlled studies in certain contexts (co-ingested with carbohydrates) to promote insulin resistance.
TL;DR: Don’t chase David Bar with a banana.
More in letter:
🚨👉What if a diet that lowered your cholesterol… increased your risk of death? (link at the end)
1/12) That’s what a forgotten a double-blind, randomized controlled trial from the 1970s seemed to show.
It tested whether swapping saturated fats for unsaturated fats would improve heart health.
Results?
The group that lowered their cholesterol... died more often. And the lower their cholesterol went, the higher their risk of death.
And if you think you’ve heard this story before (including a proper assessment of the counterarguments and deeper nuances—you haven’t…)
2/12) The Minnesota Coronary Experiment was a randomized controlled trial conducted between 1968 and 1973 that enrolled 9,423 men and women across six mental hospitals and one nursing home.
The power of this approach—though ethically questionable by today’s standards—was that researchers could truly blind and control patients’ diets with remarkable accuracy
3/12) The researcher tested whether swapping saturated fat for vegetable oil rich in unsaturated fat would reduce heart disease and death.
Butter was replaced with margarine rich in polyunsaturated fat, leading to a diet much lower in saturated fat and higher in unsaturated fat, particularly linoleic acid.
Compared to the baseline hospital diet:
👉 Linoleic acid intake increased by 288%
👉 Saturated fat intake decreased by 51%
A Nuance Hidden in a Historic Statin Trial (link in 12/12)
1/12) Medicine is supposed to treat individuals, not populations averages. And yet, the imprecision remains, like an intellectual cancer.
So, let’s look back at one of the most pivotal studies in cardiovascular history: the 4S trial, an see what is reveals when we stratify but just two biomarkers: TG and HDL
(And if you think you know where this goes, you're in for at least one plot Twist... 🚭)
2/12) According to cardiologists, the 4S trial is widely regarded as the study that launched the statin era.
4S was a randomized, double-blind, placebo-controlled study that enrolled 4,444 participants established coronary heart disease.
Patients were assigned to receive either simvastatin (20–40 mg daily) or a placebo and followed for 5.4 years.
The headline findings were that the statin (simvastatin) significantly reduced overall and cardiovascular mortality.
But there’s another part of the story—
3/12) A follow-up published in Circulation in 2001 reanalyzed 4S participants by their HDL-C and triglyceride (TG) levels as well.
“Lipid Triad” = those with highest quartile of TG + lowest quartile HDL-C
(This pattern is characteristic of insulin resistance and metabolic syndrome.)
“Isolated High LDL” = Those with lowest quartile of TG + highest quartile HDL-C
So how did these groups differ in terms of outcomes?
Dr @PeterAttiaMD recently published an article entitled, "Pitting facts against sensationalism regarding the role of LDL cholesterol in ASCVD"
1/9) Peter opens with a quote: “We must admit that our opponents in this argument have a marked advantage over us. They need only a few words to set forth a half-truth; whereas, in order to show that it is a half-truth, we have to resort to long and arid dissertations.” ― Frédéric Bastiat
I could not agree more.
That's the purpose of today's letter... to discuss Where's the Nuance, Really?!
Specifically, where is the nuance on Longevity, Cholesterol and ApoB?
What follows is a teaser for a 25 page, 4000 word "long and arid dissertations" -- linked in 7/9 🔗
Punchline: When talking about deceptive simple messaging and biased narratives, medicine should look in the mirror as well.
Let's begin...
2/9) Here's where I want to start: The three dumbest words in medicine are: “Lower is better.”
This refers to lowering LDL cholesterol or ApoB.
It’s medical clickbait—seductive, oversimplified, and deeply devoid of nuance.
3/9) But better for what? How much better? And how are we lowering it?
“Better” typically means cardiovascular outcomes only—not brain health, not metabolic health, not overall healthspan or lifespan.
“How much better” matters too. Saving 1 life per 10,000 patients treated vs 1 life per 10 treated are radically different facts in a risk‑benefit calculation—yet both get flattened into “better.”
It’s like comparing getting a double-yolk egg to the birth of your child. Stupid.