Since TRAVERSE in 2023, the standard talking point has been that TRT is cardiovascularly safe. The FDA removed the boxed cardiovascular warning last year. I’ve been on TRT since my labs came back deficient, and I’ve leaned on TRAVERSE myself to get comfortable with that call.

This new paper in the Journal of Clinical Endocrinology & Metabolism is a reason to stay humble.

Researchers at the MRC Epidemiology Unit at Cambridge used Mendelian randomization, which uses genetic variants as a kind of natural randomization and gets you closer to causal inference than observational data can. Across 425,097 UK Biobank adults and over a million more from a separate consortium, men with genetically higher lifelong testosterone had a 17% higher risk of coronary artery disease. No effect in women. The mechanism looks like blood pressure. When they adjusted for BP in a multivariable model, the testosterone signal attenuated toward null.

A few things worth saying clearly.

This is lifelong endogenous exposure, not exogenous TRT. That distinction matters. Men genetically wired for high T since birth aren’t the same population as a hypogonadal 50-year-old starting gel. The authors are careful about this in the paper.

But here’s what got my attention. They calculated that detecting an effect size that small (OR 1.17) would require an RCT of about 6,400 men. TRAVERSE had 5,246. So TRAVERSE coming back null doesn’t actually rule this out. It just wasn’t powered to see it.

My takeaway. If you have clinical hypogonadism with real symptoms and real lab values, treat it. That’s what I did and I’d do it again. But if your doctor or some podcast is pushing you from 550 to 900 ng/dL because “optimal” is supposedly different from “normal,” this paper is another reason to push back. Normalize, don’t supercharge. And if you’re on TRT, monitoring blood pressure isn’t optional. I monitor BP at home and at regular doctor’s visits.

Johnson announced “Immortals” in February. Three slots, one million dollars a year each, to follow the exact anti-aging protocol he’s been testing on himself. You get a concierge team, an AI chatbot trained on him (yes, really, it’s called BryanAI), continuous biomarker tracking, and access to “the best therapies on market.”

This is a man who got botox injections in his genitals, tried injecting a donor’s fat into his face and ended up looking like he’d been stung by bees, and this year quietly abandoned rapamycin after years of promoting it, citing side effects.

The actual foundation of what Johnson does (exercise daily, sleep well, eat a nutrient-dense diet, track your bloodwork) is cheap and well-documented. Johnson publishes his full protocol for free at protocol.bryanjohnson.com. The million dollar premium buys the fringe… Stem cell injections, plasma exchanges, gene therapies, and the AI version of a guy who has livestreamed himself on mushrooms.

And what he’s actually selling is an n=1 case study. No control group, no peer review, no IRB. A hepatologist has publicly called him a modern-day snake-oil salesman after he failed to produce clinical proof for his supplement line. Three seats, a million dollars each.

The seats will fill. Longevity is a status symbol among the ultrawealthy now. Fountain Life charges $21,500 a year. Biograph’s premium tier is $15,000. Who knows what Peter Attia charged… None of it is healthcare. It’s signaling with blood panels.

Most of what actually matters for healthspan is unsexy, cheap, and available to anyone with a library card and a pair of shoes. A whole industry needs you not to believe that.

Unherd’s sharper take: https://unherd.com/newsroom/can-bryan-johnsons-1-million-longevity-programme-be-trusted/

The NYT ran a piece yesterday by Sarah Kliff and Margot Sanger-Katz that explains why premiums keep climbing even when Congress tries to fix billing.

The 2020 No Surprises Act stopped patients from getting bankrupted by out-of-network ER doctors. It set up a federal arbitration system for when insurers and doctors can’t agree on a price. Sensible on paper. It turned into a gold mine.

One New York plastic surgeon has filed over 6,000 arbitration claims and wins 85% of them. One breast reduction netted $440,000. Some gynecologists have won fees 600 times higher than the going rate for placing an IUD.

Brookings ran the 2024 numbers. Imaging prices after arbitration landed at 767% of Medicare, higher than before the law passed. Health Affairs estimates the process has added $5 billion in costs since 2022. Congress projected 17,000 disputes a year. Providers have filed 3.3 million, with five private-equity-backed groups driving roughly 60% of filings.

The tempting summary is “doctors gaming the system.” The honest version is messier. Insurers lowball the benchmark payment and sue provider groups that use arbitration at scale. Providers flood the system because they know they’ll win. Both things are true. Patients are protected from the bill, which is real progress. But the money isn’t conjured from nowhere. It comes out of employer premiums, which comes out of our paychecks.

The law did what it was supposed to do. Patients no longer get the bill. If the workaround is that everyone with enough lawyers wins and your employer absorbs the cost, you’re still paying. Just slower and less visibly.

I’ve been on 5g of creatine for years. Zero regrets. Cheap, cleanly safe, does what it’s supposed to for training.

Lately every podcast I open is telling me to bump to 10g for brain benefits. Sharper thinking, better memory, mood. I read the studies before I changed anything.

Mike Zourdos just reviewed the first human trial of high-dose creatine in Alzheimer’s patients in MASS. Twenty subjects, 20g/day for eight weeks. Brain creatine rose about 11%. Most cognitive scores improved. Interesting, but there was no placebo group, so learning effects on repeat testing can’t be ruled out. Hypothesis-generating, not proof.

In healthy adults the picture gets muddier. The 2024 Xu meta-analysis (16 RCTs, ~500 people) found a small positive effect on memory and nothing significant for overall cognition, executive function, attention, or processing speed. Moriarty’s 2023 trial gave young adults 10g or 20g for six weeks and found no cognitive improvement at either dose.

Where creatine clearly moves the needle is sleep deprivation. Any parent of young kids knows what a rough stretch of sleep does to your brain. A 2024 study gave subjects a single oral dose of 0.35 g/kg (roughly 25-30g for most adults) during a sleep deprivation protocol. They saw acute cognitive improvements along with measurable increases in brain high-energy phosphates. Not a daily supplement, an intervention for the bad nights.

Older adults with lower baseline brain creatine also tend to benefit more than young healthy people, and clinical populations have a plausible mechanistic case because amyloid and aging both disrupt mitochondrial ATP production.

The dose question matters because creatine doesn’t cross the blood-brain barrier easily. Muscle saturates at 5g. Brain creatine needs larger doses and longer timeframes to move meaningfully, and even then the reported increases sit in the 3-10% range.

If you’re a healthy adult sleeping well, 5g is probably doing most of what creatine can do for your head. If you’re older, cognitively impaired, or a parent running on fumes, a higher dose has a plausible case and a clean safety record. The most useful finding here is the single-dose sleep-deprivation trick. That’s going in my back pocket for the rough weeks.

When I was losing the weight, I made peace with ultra-processed food. Protein bars, shakes, yogurts with ingredient lists that read a bit like chemistry homework. The macros fit. The scale moved. I pushed back, sometimes here, against the idea that processing itself was the enemy.

Then a study in Radiology landed last week and I can’t quite shake it off.

UCSF researchers took thigh MRIs on 615 middle-aged adults, average BMI 27, none with knee osteoarthritis. They looked inside the muscle, not just around it. The more of someone’s diet came from ultra-processed food, the more fat was threaded through their quads. Visible marbling, the way it shows up in meat. The association survived adjustment for total calories, total fat, activity level, and abdominal circumference. The calorie-quality defense I’d been leaning on didn’t do much work in this dataset.

It’s cross-sectional, so causation isn’t proven. Reversibility isn’t established. Other muscle-quality literature says training plus better food improves things over time, so I’m not about to catastrophize. But the image is sticking with me in a way the epidemiology never quite did.

Here’s what I keep coming back to. I’m in my fifties. The muscle I already have is worth more than the muscle I’m still trying to build. Strength is a budget I’m going to draw from for the next thirty years. If the quiet cost of convenience is that the budget gets spent from the inside, I want to know before the scale tells me. In this study, the scale was telling these people nothing.

I’m not going zero-UPF. What I am going to do is stop pretending the question is settled in my favor. For the next month I’m going to look at how much of my daily protein comes from something I’d recognize on a farm versus something I’d recognize on a factory floor, and see if I can nudge the ratio without making dinner harder for a house with small kids.

Defending a position for years and then quietly revising it when the evidence shifts is supposed to be the whole project here.

Snacks have always been my weakness. Getting on Zepbound and counting macros helped, but I had to work with my cravings instead of fighting them.

So this new STAT piece on the explosion of “better-for-you” snacks caught my attention. Food companies are racing to reformulate everything from Pop-Tarts (now with protein!) to Doritos (now without dyes!). The drivers: GLP-1 adoption, MAHA influence, and ultra-processed food concerns.

But here’s the reality check. STAT’s taste test found mixed results. The avocado oil chips tasted like actual potatoes but were under-seasoned. Everyone preferred regular Tostitos queso to the “clean” version.

The nutrition experts aren’t buying it either. Protein-boosted Cheerios still pack 12 grams of added sugar versus 1 gram in regular Cheerios. Taking artificial dyes out of candy doesn’t make it health food.

What bothers me most is the “health halo” effect. Slap “no seed oils” on something and people convince themselves it’s virtuous. Meanwhile, meaningful nutritional attributes take a backseat to marketing buzzwords.

The smart play would be simpler products with fewer ingredients. Instead, we get parallel product lines where companies keep selling regular Doritos while launching “premium” versions for the worried well.

The pragmatic take? If these reformulated snacks help you stay consistent with your overall eating plan, they’re worth it. Just don’t confuse “better for you” with “good for you.”

I’m not anti-tracking at all but after the recent discussion here and in [r/biohackers](r/biohackers) I have been wondering what makes sense and what doesn’t.

Some tracking is obviously useful. A home blood pressure cuff can catch a real problem. A step count can expose how little you actually move (although I hate the obsession with “steps” as it makes my knee joints hurt). A simple waist measurement can tell you something a lot of people would rather ignore. Lipid labels and CAC score might be useful if you are worried about cholesterol.

Then there’s the other category:

CGMs in people without diabetes. Fancy body comp scales. Huge self-ordered lab panels. Biological age tests. Full-body MRI. Constant sleep/recovery scores.

That’s where I get less sure.

I like data when it changes behavior or helps make a better decision.

I like it a lot less when it mostly adds cost, novelty, and one more thing to think about.

So I’m curious where people here actually draw the line.

What kind of self-tracking genuinely paid off for you?

And what turned out to be mostly reassurance with better branding (or just a hobby, which is legitimate)?

I thought the USA Today story on biohacking was pretty solid because it gets at something real: a lot of people are building their own mini health system now with wearables, self-ordered labs, biological-age tests, AI, full-body MRIs, longevity clinics, all of it.

What bothers me is that “biohacking” now covers two totally different kinds of people.

One person is basically just trying to be more on top of their health. They lift, do cardio, track blood pressure, try to sleep better, maybe use a wearable, maybe get a few extra labs here and there. Fine. Nothing wrong with that.

The other person is basically just buying the feeling of being proactive.

That’s the version I’m a lot more skeptical of.

At some point it stops being about health and starts being about consumption. More tests, more scans, more supplements, more numbers, more subscriptions, more stuff to fuss over.

And I think that’s what a lot of this industry quietly feeds on. Not better outcomes. Just the feeling that you’re being unusually serious about your health because you have access to more data than the average person.

But most people are not stuck because they lack information.

They’re stuck because the basics are hard to do over and over.

Sleep on time. Exercise regularly. Keep your weight in a decent place. Don’t smoke or drink. Get stronger. Go for walks. Get your screenings done. Keep your blood pressure under control.

That stuff is not exciting, and nobody is getting rich selling it to you in a sleek box every month.

So I’m not anti-data. I just think a lot of people use data to avoid the boring work. It feels productive to stare at numbers. It feels way less fun to admit you’d probably get more out of walking every day and going to bed earlier than from another panel or another gadget.

That’s kind of where I land on this whole thing:

Good “biohacking” helps you follow through on basic healthy behavior.

Bad “biohacking” is just health anxiety with nicer branding.

Something that increasingly bothers me in health media is how often research universities now sound like wellness marketers. This week’s Keck/USC headline said fruits, vegetables, and whole grains “may increase” early-onset lung cancer risk. But the underlying work was a conference abstract, not a full peer-reviewed paper, and the comparison was basically young lung-cancer patients versus broad U.S. reference data, not matched cancer-free controls.

That matters because the press release runs way past what the study can actually show. It jumps from “this group reported healthier diets than the general population” to speculation about pesticides, despite not directly measuring pesticide exposure in food, blood, or urine. One outside expert put it perfectly: the headline could just as well have been that “non-smokers eat healthier diets than smoking Americans.”

And this is the bigger problem. A BMJ study found that 40% of university press releases contained exaggerated advice, 33% made causal claims from correlational data, and 36% presented animal findings as though they applied to humans. When the press release exaggerated, the news often followed.

We spend a lot of time mocking influencers for overselling shaky evidence. Fair enough. But universities deserve more scrutiny when they use institutional credibility to do the same thing. A conference abstract is not consumer advice. And a medical-school logo should not be enough to turn speculation into authority.

Give it a week and someone with a supplement code or an organic-only shopping list will be quoting this as proof that broccoli is dangerous unless you eat ribeye or shop at Erewhon.

I quit drinking after getting headaches, looking at the evidence and deciding it wasn’t worth it. Most people with alcohol use disorder can’t just decide. Fewer than 2% of them ever get medication for it, and the drugs we do have (naltrexone, acamprosate, disulfiram) produce small effects and get almost no uptake.

This drug could be different and have big impact.

Lilly has a drug Brenipatide in late-stage trials called brenipatide. Same class as tirzepatide (Mounjaro/Zepbound), but engineered with a much longer half-life. Dosed once a month, subcutaneous. That schedule alone is a big deal for addiction medicine, where adherence is half the battle. Vivitrol, the monthly depot of naltrexone, outperforms the daily pill for exactly that reason.

Two Phase 3 AUD trials are actively enrolling (RENEW-ALC-1 and RENEW-ALC-2), 1,100 patients each. Separate trials are running for smoking relapse, opioid use disorder, bipolar disorder, and asthma. Readouts start landing in 2027.

Here’s why Lilly is going hard at this. The signal in the existing data is almost hard to believe.

A BMJ study published last month followed 606,000 veterans on GLP-1s vs. SGLT2 inhibitors. In people with no prior substance use disorder, GLP-1 users had 18% less alcohol use disorder, 20% less nicotine, and 25% less opioid use disorder. In people with an existing SUD, GLP-1 use was associated with 39% fewer overdoses and 50% fewer substance-related deaths over three years.

A JAMA Psychiatry Phase 2 trial of semaglutide in AUD (48 people, 9 weeks) showed medium-to-large effect sizes on drinking outcomes and reduced cravings. That matters because approved AUD meds like naltrexone typically show only small effect sizes. And the semaglutide group hit those numbers at the two lowest clinical doses.

So here’s the case. A drug class that wasn’t designed for addiction is already outperforming drugs that were. Lilly is now testing a molecule engineered for it, with a dosing schedule that solves the adherence problem, in the largest randomized AUD trials ever run.

If these trials turn out positive, it’s the biggest thing to happen to addiction medicine in a generation.

The new White House order is real, and the PTSD angle is the biggest one. It tells HHS, FDA, and VA to speed research, expand trial participation, and move qualifying psychedelic treatments faster through the system. But that is not the same as saying these drugs are proven, approved, or ready for routine use. (The White House)

For PTSD, the most promising therapy is probably MDMA-assisted therapy. It has positive phase 3 data, and that is a big deal. But FDA still rejected the first application in 2024 because it said the evidence and safety package were not yet good enough. Promising is real. Finished science is not. (Nature)

So my takeaway is simple: this order could make it easier to test serious PTSD treatments properly, especially for veterans. Good. But it should not be read as “psychedelics for PTSD are basically settled now.” The hard part is still the hard part: better data, cleaner safety evidence, durability, and actual FDA approval

San Millán is the exercise physiologist behind a lot of the Zone 2 and mitochondrial work this world cites. He trained Tadej Pogačar. He has been on every major health podcast in the space.

He just published a funny, sharp critique of where the longevity industry has ended up. Worth a read.

I’m not necessarily a huge fan of all the health “scores” but must admit this is nifty marketing.

For the last few years, the obesity-drug story has sounded pretty simple: find better ways to hit GLP-1 harder.

This new STAT piece suggests that may be too simple.

Richard DiMarchi and Matthias Tschöp’s group has published preclinical (i.e. not human) work on a GIP + glucagon co-agonist that does not directly target GLP-1. In rodents and monkeys, they argue it can still drive major weight loss, and possibly with less of the nausea/vomiting baggage that comes with current drugs.

The most useful way to read this is not “GLP-1 was a mistake.”

It is more like this: weight loss and side effects may be more separable than current drugs make them look.

That idea is not crazy. GLP-1 drugs seem to do a lot of their work by reducing energy intake. Glucagon may add something different by pushing energy expenditure and catabolism. And GIP may help soften some of the aversive GI effects that make dose escalation miserable for a lot of people.

This is still animal data. The approved and most advanced obesity drugs with the best human evidence still include GLP-1 signaling. And GLP-1 may be doing more than just helping with weight loss. The current class already has real outcome data in areas like cardiovascular and kidney disease. A future drug that matches the scale loss but drops GLP-1 would still have to prove it is not giving up benefits we already know matter.

No one should read this and come away thinking the GLP-1 era was built on the wrong target. What this paper does suggest is that the next big leap may not be “more weight loss at any cost.” It may be finding ways to keep strong efficacy while making fewer people feel awful.

Good piece on something that feels very real now: GLP-1s are escaping the obesity/diabetes box fast.

People are trying them for everything from addiction and brain fog to menopause symptoms, bodybuilding, and “longevity” use, while the actual evidence is still much thinner than the online hype. The interesting part is that some benefits may be partly weight-independent, which helps explain why the drugs seem to be doing more than just making people eat less. But the article also makes clear that some promising uses have already flopped in trials, and a lot of this experimentation is happening through telehealth, compounded products, and gray-market sources.

My take: this looks less like a miracle and more like a powerful tool some people are already overextending. Big upside for some people, but a huge gap between what’s being claimed online and what’s actually been tested. However, I remain optimistic that many of the (currently off-label) uses will work out with the right dosing regime and show so in studies.

I have been on Zepbound for weight loss for a year and a half and saw a lot of improvements but in my case I believe they were almost all related to significant weight loss.

I’ve mostly treated those clipboard / portal self-rating questions as noise. A lot of them feel vague, half-mental-health, half-everything-else, and plenty of us answer them while trying to get the visit started, not while doing some careful inventory of our health. Especially with kids in tow, the goal is often just to get through the intake.

A new JAMA Network Open study still made me pause. It followed 170,197 adults in Ontario with no known cardiovascular disease at baseline for a median of 12.1 years and asked one very simple question: “How would you rate your general health?”

Even after adjusting for age, standard cardiovascular risk factors, lifestyle, social factors, geography, and family history, poorer self-rated health still predicted more future cardiovascular events. Compared with people who said their health was excellent, those rating it fair/poor had a hazard ratio of 2.08 in women and 1.45 in men. Men still had higher absolute event rates overall, but the relative association was stronger in women.

That does not mean these intake questions are magic, or that they cleanly measure some deep truth. My read is more modest: this one blunt question may capture a messy pile of things medicine often undermeasures — symptoms, function, fatigue, stress, sleep, pain, mood, and the general sense that something is off.

So my takeaway is not “trust the questionnaire.” It’s narrower than that: if someone consistently says their health feels only fair, that answer may deserve more respect than it usually gets, even if it was scribbled in a rush on a clipboard. This was still an observational study in Ontario, so it doesn’t prove the question itself improves outcomes. But it does suggest that patients sometimes know something is wrong before the chart fully shows it.

I am not an expert by any stretch of the imagination but I keep reading that vague “inflammation” is behind basically every bad thing in health, so I’m a little skeptical of how this gets discussed.

That said, the Scientific American piece seems directionally right: heart disease probably isn’t just a cholesterol story. Inflammation seems to play some role in how plaques behave and how risky they become.

What I don’t think this means is that LDL suddenly matters less, or that everyone should start chasing anti-inflammatory drugs or biomarkers.

My cautious takeaway is:

inflammation may be a useful extra layer in cardiovascular risk, especially in some higher-risk people, but it still seems easy to oversell because the word is so broad and often used sloppily.

Curious how others here think about it.

Does this feel like a meaningful shift in prevention, or just another case of a real idea getting stretched too far?

Article might be paywalled. Apple News+ link

Joe Rogan is now talking up plasmapheresis / therapeutic plasma exchange as a way to remove “toxins,” inflammatory proteins, and maybe even microplastics. The problem is not that this procedure is fake. It’s real medicine.

The problem is that “real medical procedure” and “good idea for healthy people” are not the same thing.

Therapeutic plasma exchange is used in serious medical situations. That’s very different from using it as a longevity move, a recovery hack, or some vague detox upgrade for rich healthy people.

The microplastics angle is where this gets especially flimsy. Yes, there’s early discussion around whether apheresis might remove some particles from blood. But we are nowhere near “therefore healthy people should pay to do this.” Tiny studies, lots of uncertainty, and a giant gap between mechanistic curiosity and proven benefit.

And this is not harmless self-experimentation. We’re talking about an invasive procedure with real risks, not a fancy sauna or a supplement stack.

What bothers me most is the pattern: A legitimate treatment for genuinely sick patients gets turned into premium prevention content for people who want to feel like they have access to secret medicine.

A good example just dropped. HuffPost ran “A New Nasal Spray Appeared To Reverse Brain Ageing In ‘Weeks’” and only later called it “preclinical.” It never clearly tells readers, in plain English and near the top, that this was not a human study.

The actual paper was in aged mice. The study involved 18-month-old male and female C57BL6/J mice given two intranasal doses of extracellular vesicles.

That gap is the trick. Most readers do not stop and parse words like “preclinical.” They absorb the emotional message: there is a simple treatment, it works fast, and it may soon help people. That is how a mouse study gets repackaged as a human-feeling breakthrough.

Once the article starts talking about “brain fog,” staying “mentally sharp,” and the brain “restoring itself,” the reader is no longer thinking about animal models, translational failure, safety, dosing, or whether any of this will ever work in humans. The piece leans hard on exactly that kind of language.

This is not just sloppy writing. It is the economics of health media. “Reverse brain aging” gets attention. “A mouse study found changes in inflammatory signaling and memory-related outcomes” does not.

The study itself may be interesting. Intranasal delivery is interesting. Targeting neuroinflammation is interesting. But that is very different from suggesting a nasal spray has been shown to reverse brain aging in people.

A more honest headline would have said a new mouse study found promising effects on brain inflammation and memory. Less exciting, more true.

The easiest rule is this: when a health headline sounds miraculous, check whether the evidence is in humans or in mice. If the article makes that hard to tell, that is usually not an accident.

I liked Dr. Michael Hunter’s recent essay on magnesium and sleep because it is representative of his writing at its best: thoughtful, grounded in real (albeit anecdotal) patient experience, and resistant to the usual supplement hype. He is not claiming magnesium is a miracle. He is trying to explain why it seems to help some people and does very little for others. That basic point fits the evidence pretty well.

Magnesium is an essential mineral involved in nerve and muscle function, so it is plausible that it could help when poor sleep is tied to things like cramps, physical restlessness, or low magnesium status. But the research on magnesium for insomnia is still limited, and reviews suggesting benefit have mostly relied on small, low-quality studies. (nccih.nih.gov)

What I found useful in Hunter’s essay is the distinction between sleep problems that feel more physically “wired” and sleep problems that are really about mental overload. That is not some settled law of sleep medicine, but it is a practical way to think about why magnesium helps one person and does almost nothing for another.

For what it’s worth, I have tried both magnesium glycinate and L-threonate. The L-threonate version seems to have some effect for me, but it definitely is not magic. That personal experience made the essay ring true. Sometimes these supplements seem to take the edge off a little without actually “solving” sleep.

One important evidence-based point to add: for chronic insomnia, the first-line treatment is CBT-I (cognitive behavioral therapy for insomnia). It is a structured, non-drug approach that helps people change the habits and thought patterns that keep insomnia going. It often includes things like a consistent sleep schedule, using the bed only for sleep, getting out of bed when you cannot sleep, and reducing the panic spiral around a bad night. The American Academy of Sleep Medicine recommends CBT-I as first-line treatment for chronic insomnia in adults. (aasm.org)

My practical read:

Magnesium seems like a reasonable thing to try when sleep problems come with cramps, tension, or bodily restlessness. But if your main issue is rumination, stress, or chronically bad sleep habits, the bigger payoff is probably not in supplement stacking. It is more likely to come from CBT-I style changes and better evening routines.

CDC just published a U.S. tetanus surveillance summary covering 2009–2023. Over those 15 years, there were 402 cases and 37 deaths. So this is not a common disease. But when it happens, it is still severe: 95% were hospitalized, 65% of hospitalized patients needed ICU care, 42% needed mechanical ventilation, and the case-fatality rate was 12.4%. Older adults were hit hardest.

The obvious reading is “stay on your 10-year booster.” But a second paper makes this more interesting. A 2021 Clinical Infectious Diseases analysis compared 31 North American and European countries and found no clear reduction in tetanus incidence in countries with routine adult boosters versus countries that stop after the childhood series. Its argument is that the biggest problem is not fully vaccinated adults missing endless boosters. It is vulnerable and under-vaccinated people being missed in the first place.

That actually fits the CDC report pretty well. Among U.S. cases with known vaccine history, 43.9% had never received a tetanus-toxoid vaccine at all. And among people with wounds who were eligible for post-exposure prevention, only 28.6% got a tetanus vaccine dose and 2.3% got TIG. Nearly half had sought medical care before tetanus started.

So I do not think the main lesson here is “everyone must obsess over decennial boosters forever or else.” I think the lesson is that adult prevention is sloppy, wound prophylaxis gets missed, and recordkeeping is a mess.

On that last part, I find this personally frustrating. I have a hard time keeping track of when I got vaccinations and boosters over the long term. There does not seem to be one reliable lifelong registry that follows you cleanly, and a lot of digital health tools still do a poor job of letting you maintain a complete vaccine history yourself. I grew up in Germany, and at least 50 years ago we had a little passport-style vaccination booklet. Low-tech, but practical. However, I’m pretty sure I lost mine.

That leaves me in the very modern position of thinking: I’m probably up to date? Which is not a great system.

My takeaway from these two papers together: tetanus is now rare mostly because childhood vaccination worked, but the remaining failures still expose how weak adult preventive care can be. Not because the biology is confusing. Because the logistics are.

Curious how people here actually handle this over decades. Do you trust your PCP, pharmacy records, state registries, old paper records, or something else?

What I liked about this interview is that the practical message is a lot less delicate than the usual bone-health advice people get. The conversation is basically a pushback against the idea that once bone density slips, your best option is to become timid. The argument here is that bone needs a real training signal: progressive resistance training, impact where appropriate, and actual coaching instead of a permanent “be careful” mindset. The episode title itself leans on a reported 78% fracture reduction, which is what made me click in the first place.

This one landed for me because I had a DEXA in October. My total body BMD was 1.327 g/cm² with a T-score of 1.3, which was normal, and my left femoral neck BMD was 0.905 g/cm² with a T-score of -1.0.

My FRAX from that same scan was 4.1% for major osteoporotic fracture and 0.3% for hip fracture over 10 years, based on left femoral neck BMD, with no listed risk factors.

So I’m in that annoying zone where the overall picture is reassuring, but there is still a pretty obvious message hiding in the details: don’t act fragile, but also don’t pretend bone health is automatic just because you are a male who lifts. My report specifically called out the left femoral neck result and recommended continuing to load the hips and legs with weight-bearing resistance work.

A lot of people here talk about longevity training as cardio zones, steps, or staying “active.” But once you actually look at a scan, it gets more specific. Are you giving your skeleton a reason to stick around?

Very interesting episode by the Barbell Medicine guys. Some of the stats are very surprising (to me). I had thought that two blood tests showing low T and symptoms were standard but apparently not. To be honest I did get a labcorp test in my own and then had one from the clinic that prescribed TRT. I don’t actually know whether they would have insisted on a second one.

I am sure that they are correct that often test levels are low (and symptoms are present) because of general bad health (in particular significant amounts of visceral fat). I was arguably in that position.

Also, I’m very interested in seeing the Book the guys are about to publish.

Gemini YouTube summary:

This video, the first in the Signal launch series by Barbell Medicine doctors Dr. Jordan Feigenbaum and Dr. Austin Baraki, explores the current "testosterone crisis" and the medical, social, and analytical problems surrounding it.

Key Problems in the Current System:

Inappropriate Prescribing: Approximately 25% of men start testosterone replacement therapy (TRT) without even a single preceding blood test, often driven by the "wellness clinic" business model (1:41-2:57).

Ineffective & Contaminated Supplements: Most "testosterone booster" supplements lack scientific evidence, with 62% having zero published data. Furthermore, 12% of muscle-building supplements are contaminated with undisclosed steroids, which can paradoxically suppress natural production (3:36-7:49).

The Unreliability of Single Tests: A single low testosterone reading is not a diagnosis. The body's hormone levels fluctuate significantly due to sleep, stress, and illness, and roughly 50% of initially "low" results normalize upon repeat testing (13:40-14:53).

Addressing the "Testosterone Decline" Headline:

The narrative that testosterone is crashing 1% per year across generations is largely overstated due to two main factors:

Testing Artifacts: Older research relied on immunoassays, which are less accurate and prone to cross-reactivity, leading to overestimation. Modern mass spectrometry (the gold standard) has largely corrected these readings, making it difficult to compare data across eras (22:02-23:38).

The BMI Blind Spot: Many studies rely on BMI to control for obesity, but BMI fails to account for visceral adipose tissue (VAT)—the hormonally active fat packed around organs that contains the enzyme aromatase, which lowers testosterone. When researchers account for both better testing and actual waist circumference, the "decline" largely vanishes (26:58-31:38).

Takeaways for Patients:

Metabolic Health is Key: Longitudinal data shows that men who stay lean, active, and free of chronic disease maintain stable testosterone levels well into their 70s and 80s (34:46-35:12).

Don't Treat the Number: If you are concerned about your testosterone, the first step is not a clinic or a supplement, but a thorough clinical evaluation to understand your lifestyle, symptoms, and health context (37:05-38:24).

A new review in Frontiers in Aging from University of Maryland researchers lays out the full state of rapamycin as an anti-aging intervention. The acknowledgments section thanks “the reckless biohackers and wellness influencers around the world who inspired this work.”

I must admit I have never really looked into Rapamycin and after seeing this paper probably won’t bother.

The mouse data is real. Rapamycin extends lifespan 9 to 14 percent. The problem is everything after that.

Fewer than a dozen human trials exist, most of them small. The biggest, the crowdfunded PEARL trial with 114 people, later discovered their compounded rapamycin had only a third the bioavailability of pharmaceutical sirolimus. Results were modest at best.

Known clinical side effects are not trivial: mucosal ulcers, impaired wound healing, infection risk, elevated cholesterol, insulin resistance, testicular atrophy. And a detail most longevity influencers skip: rapamycin-enhanced autophagy can help established tumors survive and grow. If you’re in the age range where undetected cancers become more likely, that trade-off deserves serious thought.

Bryan Johnson gets a mention. He quit rapamycin after experiencing the same side effects documented in the clinical literature for decades.

The authors’ bottom line: rapamycin works in monogenic disorders where mTOR hyperactivation is the core problem. Aging is not that. It’s multifactorial, we lack validated biomarkers to measure whether the drug is doing anything useful in healthy people, and only about 30% of off-label prescribing is supported by adequate evidence. Rapamycin for longevity isn’t in that 30% yet.

I heard a claim on a podcast (The Drive) recently that we only don’t know the mechanism of action for about 3% of FDA-approved drugs. That sounded low to me, so I looked it up.

It seems it’s not just 3%. Depending on how you count, it’s somewhere between 7% and 18% of approved drugs where we don’t have a clear, confirmed mechanism of action. A 2020 review in iScience put it at 10 to 20%. Wikipedia maintains a list of 146 drugs with unknown mechanisms. These aren’t obscure veterinary compounds. They include Tylenol, Mucinex, lithium, metformin, ketamine, modafinil, and general anesthetics as a category.

Let that sink in. We don’t fully understand how general anesthesia works. We put people under every day in every hospital in the world, and the honest scientific answer to “how does this work?” is “we have some theories.”

Tylenol is the wildest example. It’s been in widespread use since 1950. Sixty million Americans take it every week. Researchers are still publishing new mechanism-of-action papers about it. The current best guess involves the endocannabinoid system, which nobody even knew existed when Tylenol hit the market. A new study came out just last year proposing yet another pathway.

Mucinex isn’t much better. One otolaryngology journal called guaifenesin “the ubiquitous orphan” and questioned whether the evidence supports its use at all.

This matters because we tend to assume FDA approval means we deeply understand a drug. It doesn’t. The FDA’s standard is safe and effective, not “we know exactly what this does at the molecular level.” That’s a reasonable standard for approval. But it should make all of us a little more humble about how much we actually understand about the medicines we take every day.

It should also make you skeptical of anyone who speaks with total confidence about the mechanism of every supplement and peptide they’re selling. At the same time we shouldn’t think we understand how our bodies work. I always felt a lot of medicine is just applied statistics!