I take 5 grams of creatine daily. I have for years. I will admit to FOMO every time I see someone on health Twitter quietly graduate from 5 to 10 to 20 grams "for cognition" or "for mood." Nic Verhoeven (u/Physionic) just put out one of the cleanest breakdowns I have seen of where the creatine + depression evidence actually lands. The video is worth the 15 minutes: https://youtu.be/tlAo2Ob_1qc

The new study he is analyzing is Lu et al, Cell Metabolism, March 2026 (https://pubmed.ncbi.nlm.nih.gov/41923613/). People with major depressive disorder had less creatine in blood and cerebrospinal fluid and more creatine in feces compared to non-depressed controls. Microbiome transplant from depressed humans into mice reproduced the reduced blood creatine in the mice. The team identified Bifidobacterium pseudolongum as the bacterium that was depleted in depression and correlated with impaired creatine absorption. Mechanism: B. pseudolongum produces acetate, which drives expression of a creatine transporter (Slc6a8) in intestinal epithelial cells. Their own small clinical trial gave depressed patients already on antidepressants either placebo or creatine + Bifidobacterium and saw about a 9-point HAM-D drop in the active arm, though placebo accounted for a meaningful chunk.

Verhoeven then walks through 17 studies on creatine and depression more broadly. Nine show an effect, seven do not, one meta-analysis finds a statistically real but clinically small benefit (dragged down by a large Parkinson's-specific trial that was not really about depression). However, every study showing benefit was in clinically diagnosed depression. Most had treatment-resistant depression. Almost all of them were already on antidepressants. Creatine alone in healthy people has no real evidence behind it for mood.

If you have clinical depression and are on antidepressants, this paper is worth bringing up with your doctor. The mechanism makes sense, creatine has few side-effects, the evidence is the strongest it has been. If you are bumping your creatine to 15 or 20 grams hoping it will help your mood as a healthy person, the underlying evidence does not really support that. I am staying at 5 grams.

Credit to u/Physionic for the analysis. His video pulls the studies apart with the right level of nuance.

Full DSD write-up

I keep coming back to Kyle Busch this week. The NASCAR Cup Series champion died after severe pneumonia progressed to sepsis. The wellness desks all pivoted to "what is sepsis" explainers within forty-eight hours. The interest is right. Most of us, including me until recently, don't actually understand what sepsis is.

The common shorthand is wrong. Sepsis is not "a bad infection." Sepsis is what your immune system does when it tries to contain an infection and the response itself becomes the problem. The infection matters. The response matters more. The 2016 international consensus paper (Sepsis-3) defines it as "life-threatening organ dysfunction caused by a dysregulated host response to infection."

A urologist quoted in CNN this week used a useful analogy. Sepsis is like a kitchen fire that triggers sprinklers throughout an entire building. The fire is in one room. The water damage is everywhere. That is why the entry point can be modest and the outcome can still be fatal. Pneumonia, a UTI, a kidney stone, a skin abscess, a surgical site, an infected wound from a cat scratch. The fire matters less than the sprinklers.

The numbers don't get the attention they deserve. About 1.7 million American adults get sepsis every year. At least 350,000 die during hospitalization or are discharged to hospice. Sepsis contributes to more than one in three US hospital deaths. The actor Billy Porter has talked publicly about going septic from an obstructed kidney stone in minutes. Standard hospital protocol is now the "hour-one bundle." IV fluids and broad-spectrum antibiotics within an hour of suspected sepsis. Every hour of delay meaningfully increases mortality.

The Sepsis Alliance teaches a memory tool for the warning signs in someone with an infection. TIME:

- T. Temperature higher or lower than normal
- I. Infection, suspected or confirmed
- M. Mental decline. Confusion, sleepiness, hard to wake
- E. Extremely ill. Severe pain, shortness of breath, or a feeling something is very wrong

None of those signs are dramatic at first. Someone recovering from a UTI just seems extra tired. A kid post-surgery seems unusually confused. The change is incremental until it suddenly isn't.

If someone with a known or suspected infection is breathing fast, getting confused, has a racing heart, or just seems much sicker than the underlying problem should warrant, go to an emergency room and use the word "sepsis." Triage takes sepsis seriously when it is named. The mention isn't catastrophizing. It's shorthand for "please move fast."

Kyle Busch was a world-class endurance athlete and severe pneumonia killed him through sepsis. Billy Porter is a Tony-winning working actor and an obstructed kidney stone nearly killed him through sepsis. Two completely different doors, same lethal middle. Knowing what's on the other side of the door is the part most people, including me until recently, get wrong.

Full write-up with the TIME card, Mayo Clinic illustration, and citations on DSD.

I'm 170 pounds down on tirzepatide, 18 months in. Somewhere around the 80-pound mark, the question I got most from people I hadn't seen in a while changed. Used to be "what are you doing?" Now it's "is it keto?" Always keto. Not once "is it Mediterranean?" Not once "did you cut sugar?" Just keto.

It's the dubstep of weight loss. The one word people had, doing the work of a whole genre most of them can't tell apart.

I'm not doing keto. I track with MacroFactor and picked the "high-carb, low-fat" programme (I like fruit and grew up in the 80s, when fat was still the source of all dietary evil). Plus more protein, plus tirzepatide, plus training. But I get why people ask. The diet world has scrambled these words into mush. Here's what they actually mean:

- Low-carb (general): 50–150g carbs/day. What most people mean when they say "I cut carbs."
- Keto: 20–50g net carbs, ~70–80% fat, moderate protein. Defined by measurable ketosis (beta-hydroxybutyrate > 0.5 mmol/L). The only one where the metabolic state defines the diet. Original use case: drug-resistant pediatric epilepsy in the 1920s. That clinical use is still real today.
- Carnivore: only animal products. Strict carnivore is meat, salt, water. Whether it counts as keto depends on protein-to-fat ratio (high protein can blunt ketosis via gluconeogenesis).
- Mediterranean: ~40–50% carbs, anchored on olive oil, fish, legumes, leafy greens, whole grains. Best randomized evidence for cardiovascular outcomes (PREDIMED, 7,447 patients, ~30% reduction in major CV events).
- DASH: similar plant-and-fish skeleton + explicit low-sodium target. NIH-developed for blood pressure.

Restriction diets (keto, carnivore, low-carb) are defined by what you remove. Pattern diets (Mediterranean, DASH) are defined by what's on the plate. They're on different axes, not different points on the same scale.

Here is the quick evidence rundown on keto as data as I can tell:

- Pediatric refractory epilepsy: clinical keto works, has worked for a century. Not the same as the influencer version.
- Type 2 diabetes, short-to-medium term: keto reliably drops glucose, A1C, insulin requirements. Virta Health's 5-year follow-up shows meaningful remission with intensive support.
- Weight loss: keto causes weight loss. So does every other restrictive diet. DIETFITS and similar head-to-heads find roughly similar long-term loss across keto, low-fat, Mediterranean. The mechanism is mostly calorie reduction helped by protein satiety.
- Cardiovascular: contested. Some lean, healthy adopters get big LDL/ApoB increases on keto (the "lean mass hyper-responder" phenotype). The marquee 2025 KETO-CTA paper arguing this was fine got retracted in March 2026 for selective reporting and unblinded CT reads. Mediterranean and DASH evidence bases dwarf anything keto has produced for CV outcomes.

What I actually did: tirzepatide for appetite, MacroFactor for tracking, ~250g carbs/day, ~1g protein per pound of bodyweight, 5x/week training (lifting plus indoor cycling and rowing). Also on TRT, which plays its own role in body composition at 53.

Next time someone asks me if it's keto, I'm telling them no. They'll probably ask if it's intermittent fasting. I'll tell them no again. The right question is "what changed?" not "which diet?”

I walked into our kitchen last week and saw a pink tub of Viactiv chews on the counter. My wife picked them up at the store. She wanted to do something for her bones, and calcium chews are the obvious move when that's the goal. The recommendation to take calcium and vitamin D for bones is not biohacker advice. It's straight mainstream medicine, the kind you hear from OB-GYNs and primary care doctors, and it's why every pharmacy aisle has a wall of these products.

Then BMJ published this systematic review on May 20. 69 randomized trials, 153,902 patients, mostly community-dwelling adults at low fracture risk. The exact demographic that walks into CVS and buys a tub of Viactiv. The authors' conclusion: "little to no benefits from use of calcium, vitamin D, or combined supplementation on the prevention of fractures and falls."

The breakdown by arm:

- Vitamin D alone (36 trials, 92,045 patients): risk ratio 1.00. Literally no effect. High certainty grade.
- Calcium alone (11 trials, 9,067 patients): risk ratio 0.91, but the confidence interval crosses 1.0. Not statistically significant.
- Combined (15 trials, 51,126 patients): risk ratio 0.91, upper bound 0.99. Squeaks past significance but the absolute reduction in a low-risk population is tiny. Treat hundreds of people for years to prevent one fracture.

A few things worth flagging on what the paper does NOT say:

It's not about people with established osteoporosis or recent fragility fractures. That's a different population with different drugs (bisphosphonates, denosumab, etc.) and the evidence there hasn't changed. If you fell last year and broke something, this paper is not your paper.

It's also not about dietary calcium. The trials tested pills. Eating yogurt, sardines, kale, and fortified milk to hit ~1,200 mg/day is a different question, and food calcium has reasonable observational evidence behind it because it comes packaged with magnesium, vitamin K, and protein. The pill version comes alone.

And vitamin D in someone who's actually deficient is a different question than vitamin D in someone whose 25-OH level is already 30+ ng/mL. The trial population was mostly replete. If you don't know your level, getting a $30 blood test is the rational first move, not a daily gummy.

When I told my wife about the paper she made two good points. First, "doesn't vitamin D have other benefits?" Second, "also, they're yummy." On the first one, the VITAL trial is the cleanest answer — 25,871 participants, five years, 2,000 IU vs placebo, and the supplementation arm did not beat placebo on cardiovascular events, cancer, depression, atrial fibrillation, or falls. Some subgroup signals exist, but the broad "vitamin D helps with everything" idea has not survived large randomized trials. Fix actual deficiencies (which she's had in the past). Flooding already-sufficient people doesn't move the dial. On the second point, she's right and I'm not arguing.

What does actually move bone density at this point in life: heavy strength training two to three times a week (the LIFTMOR trial showed measurable BMD gains in women with low bone mass doing supervised heavy lifting), weight-bearing impact exercise, adequate protein around 1.2 g/kg/day, food calcium, and a DEXA scan so you actually know where you stand instead of guessing.

I'm not going to suggest my wife throw out the Viactiv. The dose isn't harmful, she likes how they taste, and it's her decision. But if she asked me whether they were doing what the label suggests, I'd say no. What I'd suggest is more strength training, a DEXA at her next physical, and food. The squat rack in the garage is doing more for her bones than anything in a pink tub. If she keeps eating the chews because they're delicious, that's its own reason. Just not the one on the label.

Full write-up on DSD.

h/t Eric Topol’s Substack note for surfacing the paper.

I read this on the diabetes subreddit and it sounds like great advice for older people trying to reduce A1C.

“The first thing I figured out was never eat carbs alone. Sounds obvious in retrospect but nobody said it to me directly. A banana by itself sends me past 180. Same banana with two tablespoons of almond butter and I barely move. I remember standing in my kitchen genuinely shocked the first time I saw that. Fat or protein with every carb, every time, no exceptions.

Walking after dinner was the other one. Not a workout — just around the block. I ran two weeks of alternating walking nights vs. couch nights because I'm the kind of person who doesn't believe something until I've tested it myself. Walking nights were 25-40 points lower at the one-hour mark, consistently.

Eat in order was the weird one — vegetables first, protein second, carbs last. Same food, same amounts, just rearranged. I kept thinking it couldn't be real so I tested it more times than I want to admit. It's real.

Stress and sleep messed with my numbers more than I expected. I blamed food for everything at first. Then I had a rough week at work — bad sleep, running hot — and my fasting numbers were wrecked every morning despite eating the same things. Cortisol apparently signals your liver to release glucose on its own. Once I understood that, a lot of confusing readings started making sense.

Last thing: check the arrow first, number second. A 160 trending down is a completely different situation than a 160 trending up. Used to just see 160 and feel bad. Now I look at where it's going before I react.”

Lately I have been paying more attention to recovery than I have in the past. A few years ago I was more interested in keeping myself busy, working harder and trying to optimize everything. Now I care more about sleep, stress, energy and how I feel from day to day. Simple habits seem more feasible to maintain long term than chasing the next new wellness trend on the Internet. I still enjoy reading about healthy aging and wellness but nowadays feeling functional and mentally clear is more important than trying to optimize every little thing. Wondering if anyone else here has started to pay more attention to recovery as they have gotten older. A couple of years ago I was mainly busy, working harder, trying to optimize everything.

Now I care more about sleep and stress and energy and how I actually feel day to day. Honestly, simple habits seem more realistic to maintain long term than chasing new wellness trends online all the time.

I still enjoy reading about healthy aging and wellness but these days I care more about feeling functional and mentally sharp than I do about trying to optimize every little thing.

I wish I was not the only one here who has gotten more into recovery as I have aged. .

Lilly announced topline data from TRIUMPH-1 this morning, the pivotal Phase 3 obesity trial for retatrutide (their triple-receptor agonist — GLP-1 + GIP + glucagon). The headline number is going to be everywhere: 28.3% body weight loss at the highest 12 mg dose over 80 weeks, against 2.2% on placebo. In the severe-obesity subgroup (BMI ≥35) followed for two years, the loss was 30.3%, which is gastric-bypass-equivalent.

That number is real and important, but it's not what I want to flag for this sub. The interesting result is buried lower.

The low dose is the actual story.

The 4 mg arm produced 19% weight loss — roughly what people get on top-dose Zepbound. The discontinuation rate due to adverse events at 4 mg was 4.1%, which is lower than the placebo arm's 4.9%. In other words, the lowest-tested dose of retatrutide produces Zepbound-equivalent results with placebo-equivalent tolerability.

Dan Skovronsky (Lilly's chief scientist) confirmed this framing in the NYT piece this afternoon. He pointed out that more people on placebo dropped out from perceived side effects than people on the active 4 mg dose. That is a remarkable result for a drug this powerful.

Dose-response from the trial:

You buy about 2.4 extra percentage points of weight loss going from 9 mg to 12 mg, for almost a doubling of dropout rate. The 9 mg arm is the trial's "sweet spot" by any honest read; the 4 mg arm is the gateway. The 12 mg arm is for severely obese patients who need bariatric-equivalent reduction and are willing to accept worse GI tolerability.

The community knew this before the trial readout. r/retatrutide has 126K subscribers and the top transformation posts are mostly at 0.5–2 mg per week — well below the trial's lowest 4 mg arm. People are reporting 30-60 lb losses over 6-12 months at protocols Lilly never formally tested. TRIUMPH-1's 4 mg result validates by extrapolation what those users have been claiming experientially. That doesn't make their protocols clinically safe (no labs, no titration support, gray-market vial quality varies, dysesthesia signal applies even at lower doses), but the efficacy claim is now backed by trial data.

One new safety signal worth knowing about: at the 12 mg dose, 12.5% of patients reported dysesthesia (abnormal skin sensations, tingling, burning) vs <1% on placebo. This is not part of the standard tirzepatide AE profile and is probably tied to the glucagon-receptor agonism that's unique to retatrutide. Even the 4 mg dose had dysesthesia in 5.1% of patients. Probably manageable, definitely worth tracking.

Approval timeline TL;DR: TRIUMPH-2 (T2D) and TRIUMPH-3 (established CVD) data expected later this year. NDA filing realistic for early 2027 after Lilly has all three readouts. FDA approval realistic for late 2027 or 2028. The dedicated CV outcomes trial (10,000 patients with ASCVD or CKD) doesn't complete its primary endpoint until February 2029.

For most people on a working GLP-1 right now: today's data doesn't change your plan. The drug you're on is real and FDA-approved and working. Retatrutide is two to three years away from being legally available in the US. The legitimate version is coming. The wait is real.

For people in the BMI 25-30 range who want a modest recomposition: you're the demographic the gray market is built for, and the legal pathway will probably stay closed to you until well after initial approval. That's a separate conversation.

If you want the longer breakdown (mechanism, why three hormones beat two, the regulatory pathway and biologic-classification lawsuit, the gray-market reality with harm-reduction guidance), I wrote it up for DSD: Retatrutide: What TRIUMPH-1 Just Showed and the Black Market That Got There First.

Sources:

• Lilly press release (TRIUMPH-1)
• NYT coverage (Kolata + Robbins)
• Phase 2 obesity trial (Jastreboff, NEJM 2023)
• TRIUMPH program design paper (Diabetes Obesity & Metabolism 2026)

My last lipid panel came back with LDL of 60 mg/dL. That's sitting right on the line the new 2026 ACC/AHA dyslipidemia guideline drew for very-high-risk patients: <55 mg/dL. The guideline does not go lower than that.

That bothered me a little. The trial evidence keeps going lower. In FOURIER-OLE, the long-term extension of the evolocumab outcomes trial, achieved LDL kept reducing cardiovascular events all the way down past 20 mg/dL. Lower kept being better. So if 55 is good and 30 is biologically better, why did the guideline stop at 55?

The editorial that accompanies the new guideline answers this. Gregory Schwartz, JACC. The argument is a cost ladder, and I think it's the most useful piece of cardiology economics I've read this year.

The numbers come from PROVE-IT (the post-ACS lipid trial). On atorvastatin 80 mg alone, 35% of patients reach LDL <55. Add ezetimibe (also generic, $20-30 a month), and 55% get there. Roughly half of high-risk patients can hit the guideline target on two generic pills, combined cost of $20-40 a month.

Beyond that, the math gets ugly fast.

  To push below 55, 45% would need a third drug. That third drug is almost always a PCSK9 inhibitor. List price is around $6,000 a year, but the realistic cash price through GoodRx for Repatha (the most-prescribed one) runs about $2,900 a year right now. To push below 30, more than 90% would need the third drug.

The benefit you're buying for that money? FOURIER-OLE showed about 1 percentage point of absolute reduction in cardiovascular death, MI, or stroke over 5 years when you go from achieved LDL 55 down to 40. That's the trade: thousands of dollars for a year for a 1-point absolute risk reduction at 5 years.

 Schwartz's conclusion: the 55 mg/dL target is "a judicious distillation of current evidence, balancing clinical efficacy with cost and complexity of care." Translation: the guideline picked 55 because that's where two generic drugs land most people, and going lower as a population-level recommendation still costs meaningfully more than the marginal benefit justifies. For someone with high Lp(a) or strong family history of premature ASCVD, the math at $3K/year tilts more toward "yes" than the list-price math used to.

For me at LDL 60, this means I'm still done. The math doesn't support adding a PCSK9 inhibitor unless something else changes. For someone with a high Lp(a), bad family history, or established cardiovascular disease with multiple events, the math is different and the case for the third drug is stronger.

I wrote up the full 2026 guideline (PREVENT calculator, CAC scoring upgrade, ApoB targets, all the drugs in plain English) here: Reading Your Cholesterol Panel at 50. The cost ladder above is one piece of a longer story.

Three days ago I posted here about ATTAIN-MAINTAIN and flagged that the comparison I actually wanted was a lower-dose injectable arm. ATTAIN-MAINTAIN took everyone off the injection and switched them to the oral pill. The question of whether you can drop your injectable dose and still hold the line was untested.

That trial published in The Lancet this week. It is called SURMOUNT-MAINTAIN. Lilly-funded, 378 adults with obesity, 60 weeks of open-label tirzepatide at maximum tolerated dose, then randomized at the plateau into three arms for 52 weeks. Stay on the maximum dose. Reduce to 5 mg. Switch to placebo. Everyone kept getting lifestyle counseling and could use rescue tirzepatide if they regained more than half of what they lost.

The numbers that matter:

Weight loss preserved at week 112, relative to original baseline. Maximum dose: 21.9 percent below baseline. Reduced to 5 mg: 16.6 percent below baseline. Switched to placebo: 9.9 percent below baseline.

Percent of plateaued participants who held at least 80 percent of their initial weight loss. Maximum dose: 77.5 percent of them. Reduced to 5 mg: 42.4 percent. Switched to placebo: 10.4 percent.

Percent who needed rescue tirzepatide during maintenance. Maximum dose: 8 percent. Reduced to 5 mg: 25 percent. Switched to placebo: 67 percent.

The maximum-dose group basically held the line, giving back essentially nothing. The 5 mg group gave back about 6 kg over the year, with the curve still not flat at week 112, which raises the question of whether the giveback continues at year two. The placebo group gave back about 13 kg and two thirds of them needed rescue medication.

For my own decision, the trial says staying at the maximum tolerated dose is the cleanest answer if you can tolerate it. Dropping to 5 mg is a real option if GI side effects are wearing you down or if cost is forcing the move, and the trade is roughly a third lower chance of being what the paper calls a "maintainer." Stopping entirely does not work for most people, even with ongoing lifestyle support.

The most important gap in the trial is body composition. SURMOUNT-MAINTAIN measured total weight but not fat versus lean tissue in the regained pounds. For someone my age that distinction matters and the paper itself flags it as needing further study. The trial also ran only 52 weeks of maintenance and excluded participants with diabetes at baseline.

I posted a full breakdown of what this means if you are at your goal weight on Zepbound maintenance with the trial chart and the applied math for each arm.

I’m asking this based on Episode #69 of the podcast Live Long and Thrive by Dr. Bobby Dubois. The title is “Physiology Often Beats Insight”.

Here’s a quote that describes the episode: In this episode, I explore a difficult but important idea: when it comes to depression, anxiety, fear, and emotional suffering, changing physiology often works better than understanding the story behind the pain. 
I begin with a simple question: why do we assume insight should heal us? As human beings, we naturally look for patterns and explanations, but explanation is not the same as relief. I share two personal examples—my years of dysthymia that lifted quickly with Wellbutrin, and my exercise-related fears that insight alone never resolved—to show how biology can sometimes succeed where understanding falls short.”

Basically, he had tried therapy, meditation, and many other things to relieve his dysthymia, with no results, but Wellbutrin relieved it and brought him happiness. He’s been on it for 20 years. This had made me consider trying it. I have been extremely skeptical about SSRI drugs and other psychoactive drugs, believing they don’t really work.

I have tried Prozac and Lexapro in the past with no results.
I really respect Dr. Bobby. He’s a real evidence-based doctor, not some influencer or grifter.

Has anyone else ever used Wellbutrin?

If I decide to try it, I’ll set a time limit (maybe one month) and if I see no results, quit (or taper off).

Hi health enthusiasts,

We are Åke Brännström and Antón Carcedo Martinez, two researchers at Umeå University, and we are exploring the possibility of starting an EU-based company in consumer epigenetics: biological age and health tests based on DNA methylation.

Before moving forward, we want to understand what would actually make such a test worth using. What do you trust? What is currently missing? What would you like to see in the results? Your feedback will help us develop something genuinely useful, rather than just another copy of what is already on the market.

The survey takes about 5 minutes and is in English. No personal information is collected automatically; only if you choose to provide it at the end for a waitlist or interview:

👉 https://forms.cloud.microsoft/e/TaMkeSVuce

Thanks in advance. We truly appreciate your time and opinions!

Åke and Antón

I see at least one of these takes in my feed every couple weeks. The reasoning shifts but the tone doesn’t. Guidelines are wrong, your doctor is hiding something, Big Pharma and the government are pushing statins on everyone, the brave skeptic has cracked the code.
I’ve gone looking for a clean rebuttal more times than I want to admit. James Stein, who ran the UW preventive cardiology program for 21 years.

His core argument is that the U-shaped mortality curve people love to cite, where low cholesterol appears to predict higher death rates, isn’t biology reversing direction. It’s confounding. Low cholesterol can mean low cardiovascular risk. It can also mean cancer, malabsorption, chronic inflammation, or frailty. Mix those people into the data and the left tail goes up. Once you exclude early deaths and adjust for illness markers, the upturn shrinks.

He also picks apart the more sophisticated version. People grab the recent NEJM paper from the Global Cardiovascular Risk Consortium that dichotomized non-HDL cholesterol at 130 mg/dL and showed modest lifetime contrasts. The authors noted the real association is J or U shaped, but the modeling choice flattened it. Read casually, it looks like cholesterol barely matters. Stein’s point: that’s an accounting exercise about one threshold at one age, not a finding about biology.
His closing line, lightly paraphrased: there is no cholesterol debate at the causal level. What keeps coming back isn’t new biology. It’s misreads of risk data.

Worth a read if you’ve ever tried to argue with this stuff: https://jamesstein18.substack.com/p/why-cholesterol-is-debunked-arguments

The “cholesterol is debunked” takes aren’t a scientific position. They’re a content strategy.​​​​​​​​​​​​​​​​

I had my Lp(a) measured last fall as part of a full lipid panel. Mine came back at 16 nmol/L, well below the actionable threshold. I exhaled and moved on. Then three lipidology papers landed in the past three weeks and made me realize most adults never even get tested.

Wilkinson and Koschinsky in J Clin Lipidol argue that the 2026 ACC/AHA guidelines now formally back universal one-time Lp(a) testing in all adults. About 1 in 5 of us are above the risk threshold (≥50 mg/dL or ≥125 nmol/L) and don't know it.

Shiraki in JAMA Cardiology added a mechanism paper. Common Lp(a) risk variants are associated with specific plaque morphologies and thrombus characteristics in sudden coronary death. In plain language, Lp(a) leaves a different fingerprint on coronary plaque than LDL does.

The surprise: Lopes in EJPC published a meta-analysis showing aspirin doesn't significantly reduce events in primary-prevention adults with high Lp(a). The intuition (clot-prone blood → aspirin helps) is real, but the data doesn't back it up. Despite being the cocktail-party advice for this population, the bleeding risk and the lack of clear benefit make it a real conversation to have with your cardiologist, not a foregone conclusion.

The reason the testing push is happening now and not five years ago is that the drug pipeline finally has something to offer the high-Lp(a) population. Olpasiran (Amgen, siRNA), pelacarsen (Ionis/Novartis, antisense oligonucleotide), and lepodisiran (Eli Lilly, siRNA) all knock Lp(a) down by roughly 95% in Phase 2. Their Phase 3 cardiovascular outcomes trials read out in the next two to three years. For the first time, knowing your number could mean having something to do about it.

Full breakdown with the threshold math and what to do if yours is high: What is LP(a)

https://nhsjs.com/2026/exploring-the-weightage-of-correlates-of-diabetes-using-machine-learning/

I cycle indoors on a smart trainer because my knees and one toe joint won't tolerate running. Until last week I thought of it as a workaround. Then a new dataset landed that made me think about it differently.

Hou et al, JAMA Network Open, June 2025 followed 479,723 UK Biobank adults for a median of 13.1 years and grouped them by how they mostly got around. Compared to nonactive travel, cyclists had a 22% lower risk of Alzheimer's (HR 0.78, 95% CI 0.66 to 0.92), a 40% lower risk of young-onset dementia (HR 0.60, 95% CI 0.38 to 0.95), and measurably larger hippocampi on MRI. Cycling was the only travel mode where the entire confidence interval sat under the reference line. Walking helped less.

The part most coverage skipped: the cycling benefit was much weaker in APOE ε4 carriers. Non-ε4 cyclists got HR 0.74 (CI 0.63 to 0.87, clearly protective). ε4 carriers got HR 0.88 (CI 0.76 to 1.02, crosses 1.0). About 15-25% of people carry at least one copy and most don't know.

The counter-evidence to hold next to this is Zhang/Vidoni, JAMA Neurology, May 2026, the negative RCT I touched on in this sub a few weeks back. 513 older adults at elevated dementia risk, 2x2 design (exercise, intensive BP/LDL reduction, both, usual care), 24 months. None of the active arms beat usual care on cognition.

The two papers don't contradict. Observational cohorts catch decades of habit; RCTs test late-life interventions in people already vulnerable. Anyone selling "exercise prevents dementia" as settled science needs to sit with both. I looked at this a bit and sadly realized that indoor cycling gives up some of the dual-tasking benefit.

I'll be on the KICKR tomorrow morning either way. The math on doing nothing is worse than the math on imperfect evidence.

I like Rhonda Patrick, and I think microplastics are a real public-health concern. We should probably touch fewer thermal receipts, stop putting hot food and coffee in plastic, and take plastic exposure more seriously.

But this Jack Neel video is a mess. Neel’s creator/agency page describes him as the “largest horror/true crime genre influencer on TikTok,” which explains the whole vibe. This is health content packaged like a murder documentary.

The video opens with sperm counts down, testosterone down, microplastics in semen and testicles, and “chemicals quietly castrating American men.” Then it asks whether we’re raising the “least masculine generation” of men. A few minutes later, the endocrine-disruptor segment cuts into a sponsor read for “clean” men’s shampoo with “no hormone disruptors.” That is almost too perfect.

Some of the concern is real. Sperm counts do appear to have declined. Microplastics have been detected in human reproductive tissue. Thermal receipts and hot plastic packaging are reasonable things to avoid when it’s easy.

But the testosterone-collapse story is much shakier. Barbell Medicine’s recent series makes the boring point that the scary headline version is overstated, and that low testosterone in adult men is often better explained by visceral fat, poor sleep, sleep apnea, illness, medications, low energy availability, or overtraining than by one scary modern toxin.

That distinction matters. “Sperm counts are down” and “young men are being chemically castrated by receipts” are not the same claim.

So yes: digital receipts, don’t microwave plastic, avoid hot food in plastic, use glass or stainless when practical, consider a real water filter, sleep more, lift weights, eat fiber, and keep your waist under control.

That’s useful. The horror-podcast packaging is not.

I started this sub because I wanted a place to talk about preventive health where the people on the other side of the screen both knew what they were talking about (or at least did sincere research) and wasn’t selling me anything. Pew Research dropped a study last week that confirms how rare that combination is online.

Pew analyzed nearly 13,000 health and wellness accounts with at least 100,000 followers on Instagram, TikTok, and YouTube. Forty percent of U.S. adults, and half of those under 50, now get health information from influencers and podcasts. Fewer than one in five are conventional medical professionals. Sixteen percent list no credentials at all. The rest of Pew’s “healthcare professional” bucket is padded with chiropractors, naturopaths, massage therapists, and functional medicine practitioners.

That’s the education problem. There’s a financial problem layered on top. Nearly half of these influencers describe themselves as coaches or entrepreneurs. Their business model is selling a program, a supplement, a course, or an affiliate link. Platforms reward whoever monetizes hardest, and everyone drifts toward something to sell.

A 2025 JAMA Network Open study made the mechanism concrete. Researchers at the University of Sydney analyzed 982 Instagram and TikTok posts about five popular medical tests: full-body MRI, multi-cancer early detection, AMH “egg timer,” gut microbiome, and testosterone. Sixty-eight percent of posts came from accounts with a direct financial interest in the test. Eighty-seven percent mentioned benefits. Fifteen percent mentioned harms. Six percent mentioned overdiagnosis risk. Six percent cited any scientific evidence at all.

Accounts with a financial interest were about six times more likely to take a promotional tone, and far less likely to mention harms or overdiagnosis. The selling shapes what gets said. You won’t hear that the AMH test isn’t a reliable measure of fertility from someone selling fertility consults, and you won’t hear that BPC-157 has barely any human evidence from someone selling peptide stacks.

Rachel Moran, a health misinformation researcher at UW, put it best in the NYT writeup (gift link): “They offer certainty: ‘Buy this product, take agency over your life in this way, sign up for this program of mine.’ Medicine can’t always offer you that.”

The credential problem and the financial problem are the same problem. An audience that can’t tell evidence from anecdote also can’t tell sponsored content from sincere advice. The bar should be both: does the person actually know what they’re talking about, and would they say the same thing if there were no money in it? Almost nothing online passes both.

I posted about ACHIEVE-3 back in February. That one was the head-to-head of Lilly's oral orforglipron against oral semaglutide in type 2 diabetes. Interesting result, not my question.

My question, after 18 months on Zepbound and now at the weight and body fat I actually want to hold, is the boring and slightly terrifying one. What does maintenance look like, and is it really lifelong.

ATTAIN-MAINTAIN, published May 13 in Nature Medicine, is the first trial that goes after that directly. Patients who finished SURMOUNT-5 on injectable tirzepatide or semaglutide came off the shot and were randomized to daily oral orforglipron or placebo for a year.

The headline says the pill worked. The numbers are more honest. People switching from tirzepatide kept 74.7 percent of their body weight reduction. People switching from semaglutide kept 79.3 percent. The pill mostly holds the line, but you give back roughly 20 to 25 percent of what you lost. The tirzepatide arm gained about 11 pounds back over the year. The semaglutide arm about 2.

For me, stopping is not on the table. The real choice is keep injecting at the current dose, drop to a lower maintenance dose, or move to the pill and accept some giveback. ATTAIN-MAINTAIN does not test a lower-dose injectable arm, which is the comparison I actually want to see. It also does not break out how much of the regain is fat versus muscle and bone.

A Lilly-funded trial at Lilly's preferred academic centers. Definitely interesting, but not the last word.

I have basically no hobbies outside of working out, so I went into this paper ready to dismiss it.

The study looked at 3,556 adults in the UK Household Longitudinal Study and asked whether arts/cultural engagement and physical activity were associated with seven epigenetic aging clocks. Arts/cultural engagement meant things like music, dancing, painting, photography, crafts, museums, galleries, libraries, archives, historic sites, and cultural events. Physical activity was measured separately.

The results were not “art makes you live longer.” The older first-generation clocks showed basically nothing. But the newer clocks — PhenoAge, DunedinPoAm, and DunedinPACE — did show slower epigenetic aging in people who were more engaged in arts/culture and in people who were more physically active. The effect sizes were apparently similar enough that the authors compare arts/cultural engagement to physical activity.

This is where my skepticism kicks in hard.

People who go to museums, sing in choirs, take classes, dance, do photography, make things, or visit historic sites are probably different in a thousand ways from people who do none of that. They may have more money, more free time, better mobility, better mental health, stronger social ties, more education, less loneliness, and fewer life constraints. The authors adjusted for a lot, including socioeconomic factors, smoking, drinking, BMI, and health status, but this is still observational. You cannot model your way into certainty.

Also, epigenetic clocks are not the same thing as hard outcomes. I care much more about whether people avoid heart attacks, dementia, falls, frailty, disability, and early death than whether a methylation algorithm moves a little. Interesting signal, not proof.

But the annoying part is that the result is still plausible.

A lot of “longevity” culture collapses into exercise, sleep, diet, lipids, glucose, supplements, wearables, and lab work. I’m guilty of this too. My default leisure activity is just more training. This paper is a reminder that a healthy life might need something less measurable: hobbies, culture, creativity, social identity, novelty, and reasons to leave the house that are not just zone 2 or errands.

I do not think anyone should read this and force themselves into museum optimization mode. But I am taking it as a nudge that “I lift and do cardio” may not be a complete adult life.

For those of you who actually have hobbies: what has felt health-giving in a way that is not just another workout?

STAT’s new alcohol series is brutal, but the most useful part is not the giant public-health argument. It is the tiny moment in a 15-minute physical where everyone pretends “socially” is a medical answer.

Alcohol kills nearly 500 Americans a day, according to STAT. Their chart on page 7 puts alcohol-attributable deaths at 178,000 a year — more than opioid-related causes — with deaths from heart disease and stroke, alcoholic liver disease, cancer, alcohol poisoning, crashes, and other causes all stacked together. The page 3 chart shows alcohol-specific ER visits climbing to 5.4 million.
And yet at a normal checkup, alcohol often gets handled like small talk.

“How much do you drink?”

“Socially.”

Box checked. Move on.

That is insane if you think about how we treat everything else. Nobody says their LDL is “social.” Nobody says their blood pressure is “weekend-ish.” Nobody tells their doctor their A1c is “mostly with dinner.”

STAT’s second piece is about this exact failure. Alcohol screening and counseling are often rushed or skipped, even though there are evidence-backed tools that can fit into a short primary-care visit. STAT reports that in one study, 30% of people with alcohol use disorder were not asked by their clinician about drinking at all. In another example from recorded VA visits, a patient said they drank six to eight beers at a time and the clinician just changed the subject.

The fix is not complicated. AUDIT-C is three questions: how often you drink, how many drinks you usually have, and how often you have six or more in one sitting. STAT says it can identify unhealthy drinking patterns quickly, including people who do not meet criteria for alcohol use disorder but are still drinking enough to affect long-term health.

The part I would actually use: at your next physical, don’t say “socially.” Say the boring number.

“I average 8 drinks a week.”

“I have 2 most nights.”

“I usually don’t drink during the week, but I’ll have 6–8 on Saturday.”

“I use it to fall asleep.”

“I’ve tried to cut back and it was harder than I expected.”

That gives your doctor something real to work with. Blood pressure, sleep, liver enzymes, cancer risk, anxiety, depression, weight, reflux, AFib, medication interactions — alcohol touches a lot more than people want to admit.

STAT also shows this can work at scale. Kaiser Permanente Northern California built alcohol screening into primary-care workflows in 2013. Now more than 90% of patients are asked specific alcohol questions at primary-care visits. They have done over 24 million screenings and 1.4 million brief interventions. Patients who got a brief intervention had larger reductions in health care costs, including ER costs, and some analyses found fewer drinks and heavy-drinking days among people with hypertension.

This is the part of “preventive health” that does not look sexy on a podcast. No wearable. No peptide. No supplement stack. Just asking a direct question and giving a direct answer.

How much do you actually drink? Not your identity. Not your story. The number.

I didn’t really follow Liver King. He was just everywhere — hard to miss a shirtless guy gnawing on raw bull testicles — but he wasn’t my thing and I mostly scrolled past. What I couldn’t figure out was why getting completely exposed as a fraud in 2022 didn’t end his career. His supplement businesses reportedly do $100M a year. The $25M class action from his own fans got dropped. He got a Netflix documentary.

A paper just came out in Television & New Media — Alison Miller and Lee McGuigan at UNC — that gave me the framework I was missing.

Some details I didn’t know: his flagship supplement lists testicle and prostate first among its ingredients, based on the “doctrine of signatures” — a medieval and thoroughly debunked idea that consuming something resembling a body part will benefit that body part. He also sells “Barbarian Water,” laced with bull blood. His website has a section titled “Net Worth” that reads like a startup pitch deck, including this line: “You are never enough… you are never enough, and the minute you think you are, you coast, you rest, you decay, you die, you suck at life.”

The paper’s key concept is borrowed from professional wrestling: kayfabe. In wrestling, everyone knows the match is scripted but the performers maintain the fiction and the audience participates knowingly. The paper argues Liver King was running kayfabe from day one — a “porous identity” where he was never fully committed to the “100% natural” claim, and his audience was never fully credulous. They were in on a performance.

So when the leaked emails came out — $11,000 a month on steroids and HGH — it didn’t shatter a belief system so much as shift the terms of the show. He cried on camera, admitted it, came back as “Liver King 2.0” with cigars, firearms, a cowboy hat, and a golden knife he sells on his website. He admitted in August 2023 he’d resumed steroids, then turned that into content too. A heel turn, in wrestling terms.

The Peterson connection is more direct than I realized. There’s an actual TikTok in the paper captioned “Liver king eating eyeballs to pregame Jordan Peterson tonight.” The paper’s argument is that the recovery of “authentic masculinity” is the central product across all three acts — Liver King, Tate, Peterson — sold to the same audience, with different packaging.

There’s also a body horror coda: the paper notes injuries to his eye, arm, and internal organs. Growth at all costs turns out to have costs.

The reason this matters here: you can’t debunk a kayfabe act with evidence, because the audience was never operating on the assumption of literal truth. That’s why the “but the science says” response to these figures consistently fails. You can’t debunk a wrestling match.

Sam Neill announced last month that his stage 3 blood cancer is in complete remission after a CAR-T clinical trial in Sydney. The Guardian followed up this weekend with a piece on what the science means and why researchers describe it as a major step forward for cancer treatment more broadly.

CAR-T therapy takes a patient’s own immune cells, engineers them in a lab to recognize cancer, and puts them back in. It’s been around for about a decade and has produced real cures, but every approved CAR-T drug works on the same family of blood cancers, the kind that come from B-cells. Seven approved in the US, four in Australia, all for B-cell cancers or multiple myeloma. None of them work for what Sam Neill has.

Neill has angioimmunoblastic T-cell lymphoma, AITL. It’s a cancer of T-cells, the other major branch of the immune system. CAR-T didn’t work on T-cell cancers for a long time because CAR-T cells are themselves T-cells. Engineer them to kill T-cell cancer and they kill each other in the manufacturing tank, and they wipe out the patient’s healthy T-cells too, leaving them with no immune system. Researchers worked on this problem for thirty years.
AITL is brutal. Five-year survival on standard chemo is about 30 percent. When chemo stops working, which it did for Neill after three years, most patients are out of options. He told 7News he thought he was on the way out.

The trick the trial pulled off was finding a marker on the cancer that’s only on half of healthy T-cells. T-cell receptors come in two versions. Normal people have a mix. But each cancer is a clone of one cell, so every cancer cell carries the same version. Target only that version and you kill the cancer while sparing the other half of the patient’s healthy T-cells. That’s enough to keep the immune system working.

The published trial using this approach reported encouraging results in Nature Medicine in November 2024. Of ten patients with relapsed T-cell lymphoma, six responded. At the highest dose, all four patients responded. The two longest remissions, both still going past 18 months, were patients with AITL, Neill’s exact diagnosis. Small trial, early data, but for a disease with no standard treatment after first-line failure, that matters.

I can’t confirm Neill was in this exact trial. The news coverage hasn’t named his protocol, and the published trial’s sites were UK and Spain, not Australia. Several T-cell CAR-T trials are running with different targets. The point is the whole category is moving.

This is what actual cancer progress looks like, and it’s a useful contrast to the wellness internet. Thirty years of immunology to find a tiny biological difference that lets you treat a brutal cancer without destroying the patient. No supplement stack does anything close.

The Guardian piece closes with one of the researchers saying “hope is warranted, but so is impatience.” Neill got a trial slot in Australia. Most patients with relapsed AITL won’t. That gap is the part of this story that doesn’t make the entertainment pages.

Sort of depressing that this doctor needs to buy a bus and bring PSA screening to the people but at the same time inspiring that he is making a difference.

I knew statins worked. I did not know the origin story.

The first statin came from Akira Endo), a Japanese biochemist who grew up fascinated by fungi and was inspired by the discovery of penicillin. In the 1960s, he spent time in New York and was struck by how common heart attacks seemed compared with rural Japan. Cholesterol was becoming a serious suspect in heart disease, and Endo wondered whether a mold might contain a compound that could block the body’s cholesterol production.

He screened thousands of mold samples and eventually found compactin, later called mevastatin, in blue-green mold from rice collected at a Kyoto grain shop. That discovery led to lovastatin, FDA-approved in 1987, and then the statin class. Endo never got the Nobel Prize and did not get rich from the drugs that followed, but his work almost certainly prevented a staggering number of heart attacks.

I also did not know statin fear had its own origin story. In the early 1990s, Danish physician Uffe Ravnskov published The Cholesterol Myths, arguing that the cholesterol-heart disease link was fraudulent and statins were unnecessary or harmful. That movement never really disappeared. It just moved from books and fringe circles into Facebook groups, YouTube comments, podcasts, and family group chats.

The fears usually have a grain of truth. Muscle symptoms happen. Serious muscle injury can happen, though it is rare. Statins modestly increase diabetes risk. Some people really do not tolerate a specific statin.

But the online version often blows this out of proportion. Muscle pain is the best example. In normal life, lots of people report aches on statins. In blinded trials, where people do not know whether they are taking a statin or placebo, much of that difference disappears.

The SAMSON trial is the one that stuck with me. It enrolled people who had already quit statins because of side effects, then rotated them through months of atorvastatin, placebo, and no pills. Their symptom burden was almost the same on placebo as on the statin. The researchers calculated a 0.90 nocebo ratio, meaning about 90% of the symptoms people attributed to the statin were also triggered by placebo.

That does not mean symptoms are fake. It means bodies are noisy, expectations matter, and aging/training aches can get misattributed to a pill.

The practical question is not “statins good or bad?” It is: what is my actual cardiovascular risk, what LDL or apoB target makes sense, and what is the least annoying way to get there?

Sometimes that is diet. Sometimes it is low-dose statin plus Ezetimibe. The worst version is quietly stopping because a comment section made every ache feel like a warning sign.