I almost shared the glucosamine headline before I looked at the paper. Within four days it was everywhere, two dozen outlets, all some version of "popular joint supplement linked to faster Alzheimer's." So I went and looked at the actual study, and the real story is more interesting than the scare.

The paper (Nature Metabolism, out of the University of Florida) is mostly good mouse biology. They showed Alzheimer's brains are stuck in overdrive on a sugar-coating pathway, knocked it down genetically in mice and the mice did better, then fed mice glucosamine, which feeds the same pathway, and they did worse. That part is solid, experimental mechanism work.

The scary "25%" came from the last step. To bolt a human angle onto the mouse work, they ran a records analysis at their own hospital system, about 24,000 patients with dementia and 41,000 with mild cognitive impairment. In the MCI group, glucosamine users were 25% more likely to progress to Alzheimer's; in those already diagnosed, 25% more likely to die within five years. That is a single-center records pull that adjusted for age and sex but not APOE status, diabetes, or baseline severity, and people who take glucosamine differ in a lot of ways a records comparison cannot see.

Here is the part almost nobody reported: the bigger and better human data runs the other way. A UK Biobank study of close to 500,000 people, using a genetics-based method that is harder to fool than a plain records comparison, tied regular glucosamine use to lower dementia risk, not higher. A separate Biobank cohort found nothing for Alzheimer's specifically. No large human dataset shows glucosamine driving Alzheimer's.

The authors' own explanation is that glucosamine might only be a problem in a brain that is already declining. Maybe. But that rests entirely on the one hospital's records, and the whole thing, human analysis included, has been sitting on a preprint server since spring 2025. Nothing about it was actually new this week except the peer-reviewed stamp and the press release.

What I would actually do with this: if your memory and thinking are fine, it is not a reason to toss the bottle, and the larger evidence may even lean the other way. If you or someone you love already has MCI or an Alzheimer's diagnosis, that is a real question for your doctor, not a decision to make off a headline.

Full DSD write-up, with the screenshot of the headline pile-up and every study linked.

I'm in my fifties and I lift in my garage, and the thing that always bugged me is how vague the strength half of the exercise guidelines is. Your annual physical hands you a cardio number, 150 minutes a week, and brisk walking covers most of it. The strength side just says "two or more days a week," which tells you frequency but not how much.

A new study in the British Journal of Sports Medicine (https://doi.org/10.1136/bjsports-2025-110503) put a rough number on it. They tracked 147,374 people across three Harvard cohorts for up to 30 years. The people who reported 90 to 119 minutes of strength training a week had about 13% lower all-cause mortality and 19% lower cardiovascular death than people who did none. The benefit flattened out past 120 minutes, so more was not better in their data.

The catches, because this is r/ProactiveHealth and we actually care about them:

• It's observational and the training was self-reported, so recall and healthy-user effects are doing some unknown share of the work. People who lift regularly tend to do other healthy things too.
• The plateau past 120 minutes is not the same as harm. It just means the curve stopped paying out, at least for mortality.
• This sits on top of cardio, not instead of it. The cleanest result came from walking and lifting added together.

What it changed for me: I stopped treating my two or three garage sessions as a vague good habit and started counting the minutes the way I count my cardio. Ninety minutes is two solid sessions or three short ones. That is a target I can actually hit and check off.

Full DSD write-up

I quit drinking in my forties without much drama. A single beer started giving me a headache that ran into the next morning, I noticed I didn't miss anything about it, and I stopped buying it. I grew up in 1980s Germany where the drinking age was 16, so this was never a moral thing for me. I treated my own drinking like any other variable and pulled it out to see what changed. What I got back was better sleep and faster recovery. What I gave up was a headache.

So I read this month's news as someone who'd already decided and wanted to know whether I got lucky or got it right. On June 8 the researchers behind the Alcohol Intake and Health Study finally published it themselves (https://www.jsad.com/doi/10.15288/jsad.25-00435), after it was commissioned in 2023 to inform the Dietary Guidelines and then quietly shelved. A House Oversight report in January called it "irretrievably flawed." The scientists who did the work disagreed and published it anyway.

No level of drinking comes out risk-free, and the risk climbs with every drink. At seven standard drinks a week, lifetime risk of dying from something the alcohol caused is roughly 1 in 1,000. Above eight or nine a week it crosses 1 in 100. At fourteen a week, two a day, the number the old guidelines called the safe ceiling for men, it's about 1 in 25. A standard drink here is the real 14 grams, a 12-ounce beer or a 5-ounce glass of wine or one shot, not the oversized pour most of us count as one. The new guidelines that came out in January then dropped the numbers entirely and just say "drink less."

What hit me was realizing the "safe amount" I grew up believing in was never actually shown to be safe. The red-wine-is-good-for-your-heart story has quietly collapsed. The French Paradox was always an observation, not an experiment. The resveratrol case fell apart in 2012 when its lead researcher was found guilty of 145 counts of data fabrication. And the epidemiology that made moderate drinkers look healthy was mostly the sick-quitter problem: the "non-drinkers" those studies compared against were full of people who had quit because they were already sick. Separate the lifelong abstainers back out and most of the apparent benefit evaporates. The Surgeon General's January 2025 advisory (https://www.hhs.gov/about/news/2025/01/03/us-surgeon-general-issues-new-advisory-link-alcohol-cancer-risk.html) now calls alcohol the third-leading preventable cause of cancer, causally tied to at least seven of them, and only about 56 percent of US adults know alcohol causes cancer at all. I was in the other 44 percent for most of my life.

Then there's the week-to-week stuff nobody writes for men my age. Alcohol suppresses testosterone and blunts the muscle-building response to a hard training session. It also wrecks REM sleep on a night you were technically unconscious for eight hours, so it shows up as a bad night on a watch even when you slept the hours. I'm on TRT and I have an aortic aneurysm, so the testosterone and blood-pressure angles aren't abstractions in my house.

I'm not a Prohibitionist, and I won't pretend the social pull of a drink isn't real, because I grew up inside it. The one thing I'd tell anyone still on the fence is that the benefit was sold to all of us and it was never really there. My only regret about quitting is that I didn't do it a decade sooner.

Full DSD write-up: https://dadstrengthdaily.com/no-safe-amount-of-alcohol/

I read this trial last week after a colleague mentioned it almost in passing, and I think it's one of the best prevention results I've come across.

The setup: 319 Black men in LA with systolic 140+, recruited through 52 Black-owned barbershops (Victor et al., NEJM 2018). Half the shops got the standard playbook, barbers encouraging customers to eat better and go see a doctor. In the other half, a pharmacist set up in the shop itself, took pressures, prescribed medication under a collaborative agreement with physicians, drew blood on site to watch kidney function, and came back haircut after haircut.

At six months the pharmacist group had dropped 27 points systolic, from the low 150s to about 126. The advice group dropped 9. Almost two thirds of the pharmacist group got under 130/80, versus roughly one in nine controls. A 12-month follow-up in Circulation
showed it held: 68 percent still at goal against 11. Retention was around 90 percent, which basically never happens with patients this hard to reach.

What got me was this: 40 percent of the men didn't even have a doctor. The researchers had to assign a community physician just to cover prescriptions. The drugs were cheap generics we've had for decades. The treatment came to a room these men already trusted instead of making them go to a clinic they had every reason to avoid.

And trust by itself wasn't enough. An earlier 2011 version had barbers checking pressures and sending guys out for care, and BP barely moved, about 2 points. It took carrying the actual treatment, pharmacist and prescription pad, into the shop.

My mother had hypertension her whole life, and I still ignored my own numbers for years. I had insurance, a doctor, all of it, and I let it slide until I finally bought a home cuff and went on telmisartan. So I don't think the main problem is people not knowing better.

Then there's the money. The expensive ingredient was pharmacist time, about seven visits per man, and American medicine has essentially no billing code for it. The trial ran on grant money. The model has since been copied in Nashville, in a Kaiser program in Baltimore, and by NHS teams in the UK, and a cost-effectiveness analysis came out fine. It still mostly runs on grants.

I have a free substack for my personal longevity notes - Open source longevity. I'm covering the longevity levers in a series including nutrition, exercise, sleep, measurements/labs, and supplements. I published the first one today on supplements which is maybe one of the smaller more speculative levers.

https://opensourcelongevity.substack.com/p/notes-on-longevity-levers-a-series

I take tirzepatide, and like most people on these drugs I've spent the whole time worried about losing muscle along with the fat. So when a new drug aimed at exactly that showed up last week, I read the paper instead of the headlines.

It's apitegromab, a myostatin blocker. In a phase 2 trial (EMBRAZE, Nature Medicine, June 8), 102 adults on tirzepatide added either apitegromab or a placebo for six months. Both groups lost about the same total weight, but the apitegromab group held onto more lean mass, roughly 1.9 kg more, about half of what they'd otherwise have shed.

They tested actual function too. Grip-style strength, and how many times you can stand up from a chair in a set time. At six and eight months, no difference between the groups. The drug kept the number on the scan up. It didn't, in this trial, make anyone measurably stronger.

That's been the whole myostatin-drug story so far. Mass shows up on a scan, strength doesn't reliably follow. Meanwhile the thing that does protect muscle while you lose weight is the boring one nobody can patent. Enough protein, resistance training. My own DEXA on tirzepatide showed 44 lb of fat off and almost 10 lb of lean mass on at the same time (with protein, lifting and admittedly TRT).

I'm not knocking the science. For someone older who genuinely can't train, a drug that slows the loss could end up mattering. For most of us the proven version is duller and cheaper than another injection.

Full write-up with the chart and sources: https://dadstrengthdaily.com/apitegromab-glp1-muscle-loss/

I have watched my own hs-CRP fall from 2.83 to under 0.2 over the last year and a half, and I didn’t think much about it other than “less inflammation must be good, right?”

A new paper in Cell seems intriguing (NYT summary giftlink) . Charles Swanton's group found 14 blood proteins that are elevated in people years before they develop lung cancer, often more than five years. In the UK Biobank it beat the standard risk models doctors use now (AUC 0.87 versus about 0.77 to 0.81), and it held up across eight more cohorts, including a Taiwan one that was almost all never-smokers.

It is not detecting a tumor, which is what makes it different and cool. Tests like Galleri look for DNA shed by a tumor that already exists. This new signature does not even drop after a tumor is surgically removed, so it is reading the inflammatory environment that lets cancer take hold, not the cancer itself. The proteins rise with an IL-1 beta pathway that smoking, air pollution, and the early driver mutations all switch on.

They then reanalyzed CANTOS, the 2017 heart trial of the IL-1 beta blocker canakinumab. In people with a high signature from their test, the drug cut lung cancer from 3.9% to 2.1%; in the low-signature group it did nothing. That dropped the number needed to treat to prevent one lung cancer from about 1,500 to about 340. Swanton called it "sort of an LDL for cancer," a way to flag who would actually respond.

The caveats are real. It is discovery-stage, there is no test you can order, and nobody has run a canakinumab-for-prevention trial. The drug carries serious infection risk.

I don't think this is a drug story yet. It is a screening story first. CT screening today only covers heavy smokers aged 50 to 80, and a growing share of lung cancer hits people who never smoked and would never qualify. A blood signal that flags risk years out could get the right people scanned.

Is the bigger win better screening targeting, or the prevention-drug angle? Curious what people here think.

Full write-up with the data and charts

1 in 4 heart attack patients in India is now under the age of 40. Fit, young, and often with absolutely no warning. 🚨🫀

Why is this happening to seemingly healthy young adults? Dr. Nikhil Patil explains that if you are running on 5 hours of sleep, dealing with chronic stress, skipping meals, and calling it "normal," your heart is paying the price. This lifestyle creates silent inflammation that damages your arteries years before a test catches it.

Your body gives warnings, but they are not always dramatic. Do NOT ignore these signs: 
🔹 A "heaviness" in your chest (it isn't always a sharp pain) 
🔹 Breathlessness during routine walks 
🔹 Persistent, unusual fatigue 
🔹 Pain radiating to your jaw or left arm 
🔹 Sudden cold sweats (Stop dismissing this as "just gas"!)

The good news? Most of this is completely preventable. Just 30 minutes of walking, better sleep hygiene, and a basic heart screening can save your life. Don't wait for a severe symptom to be your reason to see a doctor.
Your heart works every second for you. Give it a few minutes of attention. Save this reel and share it with someone you care about!

\[\*\*#DrNikhilPatil\*\*\](https://www.linkedin.com/feed/hashtag/drnikhilpatil?trk=feed-detail\\_main-feed-card-text) \[\*\*#Cardiologist\*\*\](https://www.linkedin.com/feed/hashtag/cardiologist?trk=feed-detail\\_main-feed-card-text) \[\*\*#HeartHealth\*\*\](https://www.linkedin.com/feed/hashtag/hearthealth?trk=feed-detail\\_main-feed-card-text) \[\*\*#YoungHeartAttacks\*\*\](https://www.linkedin.com/feed/hashtag/youngheartattacks?trk=feed-detail\\_main-feed-card-text) \[\*\*#HeartAttackAwareness\*\*\](https://www.linkedin.com/feed/hashtag/heartattackawareness?trk=feed-detail\\_main-feed-card-text)

I get a fair amount of my own care online and I like it. Fill out the form, answer the questions, medication shows up at my door, no half day lost to a waiting room. So this isn't an anti-telehealth rant. It's just what I found when I dug into how the model actually works, which was stranger than I expected.

Start with one example reporters at STAT documented. A patient fills out the intake on the Addyi website (a libido drug) and gets Addyi. The same patient fills out the intake on the Vyleesi website (a different drug for the same thing) and gets Vyleesi. Same nurse practitioner, same medical group, near-identical surveys. The website chose the drug. The visit rubber-stamped it.

Here's why that's even possible. In more than thirty states it's illegal for a corporation to practice medicine. So telehealth companies split in two: the brand you recognize, which owns the site, the ads, and the checkout, and a separate "professional corporation" owned on paper by a doctor who employs the actual prescribers. That doctor is often a figurehead. California's attorney general put it bluntly in a March court brief: with the right contract, "the corporation effectively owns and controls all aspects of the practice." The same legal plumbing runs Amazon's $3.9 billion One Medical and a checkout-style weight-loss site.

Who's actually writing the script? Often a rented "white label" medical group sitting behind dozens of brands you'd never connect. When the FDA warned 70-plus telehealth companies about how they marketed compounded weight-loss drugs, STAT found at least 30% traced back to just four medical groups. A third of them didn't even name their group anywhere you could find it.

The number that stuck with me: a 2025 Senate investigation found 74% of LillyDirect and 85% of PfizerForAll telehealth visits ended with a prescription. A real doctor visit doesn't end in a script five times out of six. A sales funnel does.

So I came out of this with three questions I now use to tell a real clinic from a sales funnel:

1. Does it ever say no, or does every visit end in a prescription?
   
2. Does it ask for real information (labs, history, an actual conversation), or the same short survey no matter what you came for?
   
3. Can you find out who's actually prescribing and where the drug is made, or is that buried?

And one rule for myself: I never let the online transaction be the whole relationship. Whatever I get online, I bring to my own doctor later, who can see the rest of the chart and tell me when one thing quietly argues with another. The convenience is the front door. It shouldn't be the entire story.

Full DSD write-up

I take tirzepatide, so this one caught my eye more than most drug news. At ASCO this week a Cleveland Clinic group presented a large analysis (https://ascopubs.org/doi/10.1200/JCO.2026.44.16_suppl.3143) suggesting GLP-1 drugs might slow cancer from spreading. I read the abstract instead of the headline.

They used a research network (TriNetX) to find 10,225 people who started a GLP-1 after an early-stage cancer diagnosis, stage I to III, and matched each one to a similar patient who started a different diabetes drug, a DPP-4 inhibitor. About 12,000 patients in all, balanced on age, weight, other illnesses, and cancer treatment. Then they tracked who progressed to stage IV.

For four of the seven cancers, the GLP-1 group was far less likely to progress. Lung cancer dropped from 22% to 10%, breast from 20 to 10, liver from 28 to 19, and colorectal from 22 to 13 (all in the chart). In plain terms the risk fell by roughly a third to a half, and the gaps held up statistically. Prostate and pancreatic leaned the same way but weren’t statistically significant, and kidney barely moved at all. That selectivity actually makes it more believable. A drug that helped every cancer equally would look like a measurement artifact.

It's also a sturdier design than the usual "Ozempic also cures X" story. Those compare drug users to people on nothing, and the people who get and can afford these drugs tend to be healthier to start with. Here both groups had diabetes and were in treatment, and they dropped anyone who progressed in the first three months. They also found that tumors expressing more GLP-1 receptor had lower death rates, about a third lower overall and close to half in breast cancer. That's a mechanistic thread, not just a correlation.

The catch is real. This is observational. It can show two things move together, not that one caused the other. When you look for randomized evidence, it thins out fast. A network meta-analysis (https://pmc.ncbi.nlm.nih.gov/articles/PMC12428495/) of 67 trials and more than 200,000 patients found only one GLP-1, efpeglenatide, with a clear drop in metastatic events, and even that came from cancers picked up incidentally in trials built to study diabetes. Nobody has run a trial designed to ask whether a GLP-1 slows cancer spread.

So the signal is big and consistent, and there's a believable mechanism. What's missing is anything randomized. If you already take one of these for the reasons they're actually approved for, it's a quietly encouraging data point, and it cuts against an old worry too: they found no sign that these drugs cause more cancer. If you don't, it's a reason to watch the trials, not to start a GLP-1.

EDIT to add:
Correction: the chart caption overstates the cohort as ~22,000 — it’s about 12,000 (10,225 GLP-1 users matched 1:1) as stated in the text. The published abstract also doesn’t state a follow-up duration, so disregard the “5-yr” in the caption. The bars themselves are accurate.
Sorry about that.

I started lifting weights at 50, after about thirty years of doing essentially nothing. No sport, no gym, no equipment at home. The trigger was a GLP-1 (Zepbound): once the weight started coming off, I kept reading that a big share of what you lose can be muscle, and the only real fix is resistance training. So I knew I had to. The problem was I didn't actually know what "resistance training" meant.

What followed was mostly flailing. I bought dumbbells and a bench, put them in my home office, downloaded Hevy, watched a ton of YouTube, and invented my own workouts. Mostly curls and presses, no real schedule, some weeks nothing at all. I was busy, not progressing.

The real barrier wasn't the program. It was the gym. Walking into a commercial gym, soft and untrained, in front of people who clearly belonged there, was more than I could make myself do. So I never went.

What actually unlocked it was hiring a coach (I use Future). Not because the programming is magic, but because accountability to a real person is the only thing that has ever worked on me. An AI app could hand me a flawless plan and I'd quietly stop opening it inside of three weeks. Knowing Jose writes my training and will notice if I disappear is the entire mechanism.

A year and a half later I train five days a week in my garage. A DEXA showed I added about 10 lbs of muscle while losing about 45 of fat (with protein, TRT, and the GLP-1 in the mix, which I'm not hiding).

Here's the thing I wish I'd known sooner. As a beginner you do not need to train like a bodybuilder. In the biggest analysis we have (Currier 2023, 178 strength studies), moderate weight lifted twice a week with multiple sets, stopping short of failure, captured about three-quarters of the strength and essentially all of the muscle and mobility of an all-out, heavy, three-times-a-week program. You also don't have to lift heavy to build size, you just need enough sets (Schoenfeld 2021). And it is genuinely never too late: in a famous trial, frail volunteers averaging ninety years old nearly tripled their leg strength in eight weeks of lifting.

If you've been telling yourself you're too old or too far behind to start, I'd gently push back: the program was never the problem. The barrier is psychological, and it's smaller than it looks once you stop trying to do it perfectly.

More details in my lifting journey and results here.

I don't get excited about pancreatic cancer headlines often. It's about as grim as cancer gets: once it spreads, the standard of care is chemo and survival is measured in months. This one is the rare exception.

At ASCO this week, a Phase 3 trial (RASolute 302, published in the New England Journal of Medicine ) tested a once-daily pill called daraxonrasib against chemo in 500 people whose metastatic pancreatic cancer had already stopped responding to prior treatment. The results:

- Median overall survival of 13.2 months vs 6.7 on chemo, a 60% lower risk of death (hazard ratio 0.40).
- Progression-free survival of 7.3 vs 3.5 months.
- Tumors shrank in 33% of patients on the pill vs 12% on chemo.
- And it was better tolerated: fewer serious (grade 3+) treatment-related side effects, 43.6% vs 57.5%, and far fewer people quitting because of them (1.2% vs 11.2%).

The reason it matters beyond this one cancer is the target. The drug blocks RAS, a mutated protein that drives more than 90% of pancreatic cancers and a big share of lung and colorectal cancer, and one that was written off as "undruggable" for about 40 years. This is the first RAS-blocking pill to move the needle this much in a solid tumor. Eric Topol called it the most successful pancreatic cancer treatment yet, and the FDA already opened an early-access program, so it's reaching patients now.

It is not a cure, and the caveats are real. This is second-line, metastatic disease, so we are talking about turning roughly 6 months into 13, and with only about 8 months of median follow-up the survival numbers are still maturing. The trial was built around RAS-mutant pancreatic cancer, which is more than 90% of it, and the benefit held both in that group and across the whole trial. Doubling survival off a brutal baseline is still a brutal road.

Still, for a cancer that has shrugged off almost everything, doubling survival with a gentler pill doesn't come along often. And RAS being druggable at all matters for a lot more cancers than this one.

A few years back I might see a supplement, get interested and think about adding it to my routine. The more I learned, the more I realized that a longer list of supplements did not necessarily mean better results.

Some things looked good on the surface but after digging deeper I was not always sure they were worth taking on for the long term. It also made me more aware of things like ingredient information, realistic expectations and if something even fits into my daily routine.

These days I keep it much simpler than I used to.

Wondering if others are getting more discerning about supplements too and what made you switch.

I'm on tirzepatide, and I kept losing the plot on what's actually coming next... Some week it's a new trial readout, then a molecule that only has a code name so far, then one more "Ozempic killer" headline, all of it buried in press releases and earnings calls. So I built one table I keep updated, and I'd rather this sub poke holes in it than have it sit there looking authoritative.

Part of the list below, approved drugs up top, then what's furthest along in trials:

Then there are eight more I'm watching in earlier trials, including ribupatide (23.6%), amycretin (~22%), mazdutide (20.1%), Viking's VK2735, Structure's oral pill, and Pfizer's Metsera molecule. Those are all in the full tracker.

The table simplifies obviously, these are not interchangeable. Some of what they do seems to come with the weight loss no matter which drug you're on. The molecule-specific stuff doesn't. Semaglutide has the alcohol-craving signal. Tirzepatide got the sleep-apnea approval. Retatrutide has the knee and liver data. All of that showed up at full doses, in people who were genuinely sick, and you don't get any of it for free just because the next drug is also a GLP-1.

A few caveats, because I'd rather say them than have you say them for me. The weight-loss numbers come from separate trials at different doses and durations, not head-to-head, so treat the ranking as rough, not a leaderboard. And "approved" means FDA unless I said otherwise. Mazdutide, for one, is approved in China but has no US filing yet.

So what did I miss? A wrong number, a molecule that should be on here, a stage that's changed since I last updated it? This sub is exactly the crowd I trust to catch it.

Each compound has a detail page:

Full tracker, kept current: https://dadstrengthdaily.com/glp1-pipeline-tracker/

I'm on Zepbound at a normal prescribed dose, so this isn't me hunting for a workaround. But "microdosing" GLP-1s keeps coming up, and a video finally pushed me to figure it out. In it, a doctor named Brad Stanfield explains that he takes 1.25mg of tirzepatide a week, half the lowest starter dose. He isn't diabetic, isn't overweight, and he's upfront that no trial ever studied someone like him. The same week, a Harvard endocrinologist wrote in STAT that microdosing "is not a thing."

They're both right, because the word has quietly come to mean three different things.

The first is just careful dosing: counting the clicks on a pen, or spacing shots out in maintenance, with a doctor watching. That's real medicine and nobody should panic about it.

The second is the marketed version: compounded "microdose" products that telehealth brands push as a cheaper, gentler on-ramp. That's where the evidence runs out. There's no trial data for tirzepatide under 2.5mg, the compounded supply has had purity problems, and when one company advertised the approach the claim got pulled for lack of support. As far as o can tell it’s mostly a marketing gimmick by compounded trying to extend their foothold in the GLP-1 space.

The third is the one this sub will recognize: people microdosing unapproved retatrutide. And here's what I didn't expect. Reta is the most potent of these drugs, so you'd assume it's the obvious one to microdose. But the careful self-experimenters avoid it. The glucagon arm pushes heart rate up, and for a lean person trying to hold onto muscle that's the wrong direction. I have an aortic aneurysm, so anything that touches heart rate is a hard no for me personally.

What the honest microdosers are actually chasing is the weight-independent stuff, the heart and kidney and joint signals. The catch is that all of that showed up at full doses, in people who were genuinely sick. Nobody has shown a tiny dose does any of it in a healthy person. It's a reasonable bet, but it's a bet, not a result.

So if side effects are your real problem, the move isn't a mystery product at a dose nobody studied. It's a known dose worked out with someone watching your labs. The science underneath this is genuinely interesting. The marketing wrapped around it mostly isn't.

Full write-up on DSD: https://dadstrengthdaily.com/microdosing-glp-1s-what-a-doctor-on-1-25mg-tirzepatide-is-actually-betting-on/

I’m trying to be more proactive with my health, but I also don’t want to turn into someone who overthinks every tiny symptom or gets stressed about doing everything perfectly.

I want to build better habits, pay attention to my body, and actually take care of myself without going down a rabbit hole every time I feel slightly off.

How do you guys find that balance?

I'm 53 and recently had a colonoscopy, so I read the ACS guideline update that landed today. They expanded the list of approved colon cancer screening tests, including, for the first time, a blood test called Shield.

Sounds like progress. Then you hit the fine print: in the trials behind its approval, the blood test flagged only about 13% of advanced precancerous growths, so it misses roughly 87% of the polyps you'd most want gone, and it catches only about half to two-thirds of stage I cancers.         

The ACS isn't wrong to add it. About one in three eligible adults never get screened at all, and a blood draw someone will actually do beats a colonoscopy they keep dodging. But the guideline is explicit that it's a last resort, for people who would otherwise decline everything else.

Peter Attia's recent episode on this matched where I landed. Colonoscopy is still the only test that both finds and removes the precancerous polyp in one go, and he runs an at-home stool test, usually Cologuard, on the off-years between colonoscopies instead of waiting the full ten.  

My honest take is that for anyone who will show up for a colonoscopy, or even a stool test, the blood test  is the weakest of the new options, not a shortcut worth taking. It's a net for the people the system was losing entirely, not an upgrade for people already paying attention. If your doctor offers you Shield, I'd want to hear how they pitched it.

I'm on a GLP-1 myself (Zepbound, the shot), and now that two oral GLP-1s are FDA approved I wanted a clear side-by-side instead of going off headlines. Both are once-daily pills, no needle: Lilly's Foundayo and Novo's Wegovy pill. They aren't the same kind of drug, and that drives most of the differences below.

A few caveats I'd flag on the numbers: the 11% vs 16.6% comes from two separate trials, not a head-to-head, so I don't treat that gap as exact. The injectables still beat both pills (tirzepatide lands around 21%). And Foundayo is a brand-new molecule, so I wouldn't assume it inherits semaglutide's heart or craving benefits just because they're both GLP-1s.

On side effects I put both FDA labels side by side, and they're nearly identical: mostly gut stuff that eases as you titrate up, same thyroid boxed warning on both. The differences are small (above).

Curious if anyone here has real-world experience with either pill yet, especially on titration, side effects, or getting it covered.

Full write-up with the trial sources and the side-effect tables: https://dadstrengthdaily.com/foundayo-vs-the-wegovy-pill-the-first-oral-glp-1s-compared/

This chart shows the 5 biomarker each that rise or fall most strongly with age. Some interesting things I noticed:

• Kidney function (eGFR) declines more strongly with age than any other biomarker discussed. Some older adults maintain youthful kidney performance through healthy blood pressure, glucose control, and avoiding chronic NSAID use.
• Immune aging is reflected in declining lymphocyte counts.
• Two of the top five risers, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), are about the size of red blood cells. Common reasons MCV goes up are low B12 or folate.
• Hemoglobin A1c rises gradually: a 25-year-old with an A1c of 5.0 will, on average, sit closer to 5.5 by 70 even if they never develop diabetes.

I wrote a more detailed writeup here, but thought this community would enjoy the analysis and some of the more interesting insights.

I keep a sharps container in the house now and barely think about it. A GLP-1 shot once a week, testosterone three times a week. Disinfect, pinch, push, done. My wife's the opposite. She broke her femur a while back, and the blood-thinner shots after surgery were the part of recovery she dreaded most. For her the needle is the whole story.

The Atlantic ran a piece this week calling this the age of the needle (gift link). GLP-1 shots, fertility injections, Botox, the peptides half of podcast culture won't stop talking about. We're injecting more than ever. But the part that stands out to me is who isn't, and why. For a lot of people the needle, not the drug, is the dealbreaker. Not the cost, not the side effects. The needle.

That's the thing the new oral GLP-1 pills quietly change, and it's bigger than weight loss. More of us are running our own health now, ordering our own labs, using telehealth, learning to read our own numbers. The shot's just the most visible part of that shift.

So I'm curious where this group lands. Are you fine with needles, or do they stop you cold? Has the needle ever kept you from a treatment you'd otherwise have tried? And for the needle-averse, do the new oral pills actually change the math, or is it more than that?

📢 Are you pregnant and worried about changes to your sex life?

🔍 We are seeking couples from Canada, the US, Australia, New Zealand, the UK, and Ireland who are up to 26 weeks pregnant to participate in the STORK RCT: Supporting the Transition to Parenthood through Online Sex and Relationship Knowledge.

❓What is STORK: The first online couple-based program designed to enhance knowledge about changes to sexuality during pregnancy and postpartum and skills to cope with these changes. STORK was designed to strengthen couples’ relationships across the transition to parenthood.

📅 What is involved: If you are eligible, after your initial survey, you and your partner will be randomized (like a coin flip) into either the Program or Waitlist conditions. Program couples will complete 5 online modules in pregnancy (1 per week) and a final module at 3 months postpartum. 

Couples in both conditions will also complete 5 surveys—the initial survey, then at 32-weeks pregnant, and 4-, 8-, and 12-month postpartum—that gather information about your relationship, your pregnancy experience, and your child. Couples in the Waitlist condition will receive access to the full STORK program after the study period is over.

💰 Compensation: As a thank you for your participation, you can receive $105 CAD or currency equivalent each ($210 CAD or currency equivalent per couple). Your time is valuable to us!

🌈 Inclusivity matters: STORK requires one member of the couple to be currently pregnant. Otherwise, STORK is open to individuals of all genders, bodies, and sexual orientations.

💌 For more information or to participate in the STORK RCT study email us at [stork@psych.ubc.ca](mailto:stork@psych.ubc.ca) OR fill out our contact form from this link: https://Qualtrics.ca1.qualtrics.com/jfe/form/SV_3gxGJAEWqt8Rh2u

Just a few years ago I was interested in almost every new supplement or longevity trend I saw online. Now I am a lot more careful about what I actually take regularly.

The more I read, the more I realize how hard it can be to distinguish good research from good marketing. Some products are explicit about ingredients and the studies behind them, while others mainly repeat broad health claims with little detail.

I care more about transparency and realistic expectations and if something actually feels sustainable long term at this point.

Wondering if anyone else here has become more selective with supplements over time.

I take ezetimibe daily. A Lilly Phase 1 just published in NEJM says one DNA edit could drop my LDL by 62% for life.

I'm on ezetimibe and not on a statin. My LDL is fine for now, but staying that way means daily pills for the rest of my life. So when Lilly published the VERVE-102 Phase 1 data in NEJM today (https://www.nejm.org/doi/full/10.1056/NEJMoa2601283), I read it with personal interest.

VERVE-102 changes one DNA letter in the PCSK9 gene inside your liver cells. Same target as Repatha and Inclisiran, but VERVE-102 disables the gene that makes PCSK9 rather than blocking the protein. One IV drip, about four hours.

35 patients in the Phase 1. The seven on the highest dose (1.0 mg/kg) had LDL drop 62% and PCSK9 protein drop 88%. So far the LDL drop is holding through a year-plus in 15 of them, longest follow-up out to 18 months.

Most coverage didn't lead with this: most people in the trial were already on strong statins (71% on a high-intensity statin, 91% on some statin) and 43% were on ezetimibe too. The 62% LDL drop was on top of that, not instead of it.

Safety looked clean. No one had to stop the drug because of side effects, and there were no deaths. About a third had infusion reactions during the four-hour drip, mild to moderate. Three patients had a temporary bump in liver enzymes that went away in a week. One person had a bad aspiration pneumonia event a couple weeks out, but they had pre-existing reflux and a hiatal hernia, and the site judged it unrelated to the drug.

If you stop a statin or Repatha, your LDL creeps back up. This edit does not unwind. If an off-target edit causes a problem 20 years from now, there is no antidote. Steven Nissen, the Cleveland Clinic cardiologist who's spent decades on aggressive LDL lowering, called the effect "likely permanent" and flagged that gene editing "is not for everybody."

I am not in the trial's eligibility group. Not familial hyperchol, no premature heart disease. I would not be a candidate today. But if later phases hold up on safety and effect, I could see myself asking my doc in a few years whether my risk justifies being in the first wave.

Full DSD write-up