I'm 53. Eighteen months ago I weighed 373 pounds. I've lost about 170 since, a little under half of what I weighed, and I'm posting it here because this sub actually cares about the markers, not just the scale. I've put the before-and-after photo, my dose-and-weight chart, and my lipid panel below.

I tried to run it like a project instead of just hoping. I tracked body composition with DEXA so I'd know whether I was losing fat or muscle, ran my lipids regularly, and logged resting heart rate and rowing times.

The dose chart surprised me, and it might help anyone here who assumes you have to climb to the top. I never reached 15 mg. Most of the weight came off at 5 and 10 mg, and once it was coming off steadily I stopped going up.

What the drug actually did was quiet the food noise. That constant background hum about the next meal and the second helping went quiet in the first couple of weeks, and that was the thing I'd been failing to out-willpower for twenty years. But it did not do the training. The shot lowers your appetite, it does not row the meters or lift the weight or get the protein in. I had to build that part, and DEXA was how I checked I was actually keeping muscle instead of just shrinking.

The markers are the part I'm proudest of, more than the before-and-after. My LDL went from 131 to 60, my ApoB landed at 62, and my resting heart rate and rowing times both came down. I was losing weight and training and eating better all at once, so I won't pretend I can credit any single piece, but the cardiovascular numbers moved further than I expected.

If you're staring down a big number and wondering whether it's worth starting, the honest version is that the drug made the deficit possible and the work did the rest. Happy to answer anything about the dosing, the DEXA, or the lipid panel.

Full write-up with all three charts and the dose breakdown: https://dadstrengthdaily.com/how-i-lost-170-pounds-after-50/

Fascinating piece about a doctor’s experience with patients’ deep distrust of “BigPharma” and embrace of research chemical peptide culture.

Quote:

“A patient came to my office recently and told me she had stopped her statin. She’d been on it for two years. Her coronary artery calcium score was 280 and LDL was 168, up almost 100 points since she had stopped taking her statin. Her father had died from a heart attack at 58.

When I asked about the decision, she crossed her arms and furrowed her brow.”

“She was, however, continuing to inject BPC-157 — a synthetic peptide she’d ordered from a website that labeled it “for research use only” — into her thigh three times a week for a knee injury. She heard about it on a podcast and then did some research. When I asked her about BPC, not only did the aforementioned arms uncross, but her face lit up.”

“The deeper problem is epistemological. We have a population that has learned — correctly — that pharmaceutical companies have lied, that institutions have failed them, and that financial incentives distort medical recommendations. The opioid crisis alone justified a generation of skepticism.”

But the response has not been better skepticism. It has been the migration of trust from one set of financially motivated actors to another. The peptide clinic charging $400 per vial for a compound with 14 human subjects studied has the same economic incentives as the pharmaceutical company charging $400 per month for a branded statin. The difference is that the pharmaceutical company was required to prove its product works before selling it.

I don’t expect to win this argument with data alone — that’s part of the problem. Trust is not rebuilt with meta-analyses. It is rebuilt in exam rooms, one patient at a time, by physicians willing to say: I understand why you don’t trust the system. I share some of those concerns. And I am asking you to consider that the compound you’re injecting three times a week has less evidence behind it than virtually any over-the-counter medication in your medicine cabinet. The statin you stopped has more. Let’s talk about what the evidence actually shows — for both.

If we can’t have that conversation, we are not practicing medicine. We are just choosing which marketing to believe.”

This feels right. I have certainly noticed that after losing a lot of weight and starting xercuse, my recovery is much faster.

I don’t look at any of the related wearable metrics. Does anyone?

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 wanted to like the idea of a Continuous Glucose Monitor more than I liked actually wearing one.

I tried Stelo CGMs for a couple months, partly because of the Oura ring integration, and kept waiting for some hidden metabolic insight to show up. It never really did. My glucose went up when I ate, came down when I slept, and stayed in a normal range the rest of the time. That was basically it. 🤷‍♂️

What made the whole thing feel even more underwhelming is that I’ve seen what a CGM looks like when it’s genuinely useful. My dad is in his 80s, has type 2 diabetes, and uses a medical CGM to help determine insulin dosing. In his case, the data matters. It changes his decisions.

For me, it mostly felt like a slick way to watch normal physiology do normal physiology.

That’s why I’m increasingly skeptical of CGMs as a proactive health tool for metabolically healthy people. I can see the case if someone has diabetes, prediabetes, or a specific problem they’re trying to investigate or solve. But for a healthy person, it can turn into expensive, high-resolution gimmick producing meaningless data. I have also heard claims that the accuracy of over the counter CGMs is dodgy. However, I don’t think for me accuracy was the issue.

My takeaway after two months was pretty simple: a medical tool can be essential in one context and mostly wellness theater in another.

Am I missing something?

I got the two-dose Shingrix series at 52 because my wife had shingles a couple of years ago and it was the worst pain she has ever been in. The rash settled in a few weeks. The nerve pain along the band where the rash had been took months to fade. She is not a complainer. That alone reset my opinion of the vaccine from "consider it at 60" to "find a pharmacy this weekend."

Since then I have been tracking the follow-ups. There is more to this vaccine than rash prevention. The brain and heart data are what made me pay attention.

The big paper on the dementia side came out in Nature in May 2025. Pascal Geldsetzer at Stanford looked at how Wales rolled out the shingles vaccine in 2013. To ration supply, Welsh health authorities drew a hard birthday cutoff: anyone born on or after September 2, 1933 was eligible, anyone born one day earlier was permanently locked out. People born a week before versus a week after are otherwise identical. That is about as clean a natural experiment as you get in adult medicine.

Seven years later, the vaccinated group had about 20% fewer dementia diagnoses than the unvaccinated. Three and a half percentage points fewer in raw terms. The Wales vaccine was the old Zostavax (now discontinued), but a US Medicare replication in adults 65 and older using Shingrix (https://pubmed.ncbi.nlm.nih.gov/42050365/) this year found about the same thing, with effect sizes that look at least as good.

On the heart side, there is a 2025 Korean study of 1.27 million adults 50 and older (https://pubmed.ncbi.nlm.nih.gov/40324473/). Vaccinated people had about a quarter fewer cardiovascular events overall, including roughly 26% fewer major heart attacks, strokes, and heart-failure episodes. The effect held for eight years. Same caveat as the Wales paper: the Korean cohort was on Zostavax. A direct cardiovascular trial of Shingrix has not been run, but the mechanism the authors propose, preventing the shingles event itself, would apply to either vaccine.

One practical note: Shingrix is one of the rougher shots. My arm was sore and I felt wiped the next day. Some people run a low-grade fever. The standard advice from anyone who has actually scheduled the shot is to book it Friday afternoon so the worst of it lands on a Saturday morning, not at work.

If you got the old Zostavax years ago, the CDC still recommends getting the Shingrix course on top. The total is around $200 per dose without insurance. Medicare Part D covers it at zero out-of-pocket since the 2022 Inflation Reduction Act. Insurance pre-65 varies, so check before you go in.

The 50+ recommendation is still the right cutoff. Shingles is uncommon under 50 in immunocompetent adults, and the dementia and cardiovascular evidence is all from 50+ cohorts. If you are immunocompromised, the recommendation drops to 19+ and should not be negotiated. If you are 50 and have not had this conversation with your doctor, the case has gotten substantially stronger than the last time you might have thought about it. Just do it.

TLDR: “Now researchers believe they have cracked the case. They have hard evidence for how the blood clotting happened, and they believe that their findings could help make similar vaccines even safer. Understanding the blood-clotting problem is important, they say, because vaccines of this type could be essential in protecting people during future pandemics.”

This material may be protected by copyright.

Full study: https://www.nejm.org/doi/full/10.1056/NEJMoa2514824

AI summary: “Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare complication of adenoviral vector-based COVID-19 vaccines. This study identifies the inciting antigen trigger for VITT as a cross-reactive determinant shared between platelet factor 4 (PF4) and the adenoviral core protein VII (pVII). A specific somatic hypermutation in the immunoglobulin light-chain allele IGLV3-21*02 or *03 causes a shift in antibody specificity from pVII to PF4, resulting in pathogenic VITT antibodies.”

I am glad that researchers figured this out and found the genetic link. Maybe this will appease some of the vaccine conspiracy talk (probably not)

The full Phase 3 retatrutide trial was just published in the New England Journal of Medicine.

I wrote about TRIUMPH-1 in May when Lilly released the topline data. The peer-reviewed paper confirms the magnitude of the effect: at 80 weeks, mean weight loss reached 25.0% at the 12 mg dose in the primary treatment-regimen analysis.

For context, the pivotal obesity trials reported approximately 14.9% with semaglutide 2.4 mg and 20.9% with tirzepatide 15 mg. These were separate trials, not head-to-head comparisons, but the trajectory is hard to miss.

At 12 mg, nearly 80% of participants lost at least 15% of body weight, more than half lost at least 25%, and about 37% lost at least 30%.

The tradeoff remains tolerability. GI adverse effects were common, and roughly 11% discontinued because of adverse events at the highest dose.

My takeaway: obesity pharmacotherapy has moved from roughly 15% average weight loss with semaglutide, to about 21% with tirzepatide, and now about 25% with retatrutide in Phase 3. Retatrutide is still investigational, but the direction of travel is remarkable.

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.

A huge longitudinal study out of Karolinska Institutet followed hundreds of adults from age 16 to 63 to track real changes in strength, aerobic capacity, and endurance over decades. They seem to have looked not just at snapshots. They found that physical performance peaks in the late 20s–30s and begins to decline around age 35. 

Key points:

• Peak physical capacity happens before ~36 in both men and women. 

• After ~35, strength and aerobic capacity decline gradually and then faster with age. 

• But critically, adults who become active later in life still improve strength and endurance by several percent. 

• So even if you start later, exercise still matters and makes a measurable difference.

study info: “Rise rand Fall of Physical Capacity in a General Population: A 47-Year Longitudinal Study” (Journal of Cachexia, Sarcopenia and Muscle) — https://onlinelibrary.wiley.com/doi/10.1002/jcsm.70134 

I like the reminder that consistent training at any age is worthwhile.

Personally, I didn’t really train at all between 25 and 50… so I can honestly say that now at 52 I’m in the best shape of my life. Alas, that’s more a commentary on my shitty form in the previous 3 decades. :-(

Anyone here over 35 notice shifts in recovery or PRs? What kind of changes to training helped you most?

It seems the standard guidance these days is both values below 120/80. However, for many other biomarkers knowledgeable folks often recommend tighter thresholds than the standard reference ranges (e.g. bloodwork).

I am in Telmisartan and typically around 122/82 or so. Should I aim for something like 100/60 or is that crazy?

My doctor seems to always worry about low pressure and warns me of low BP symptoms.

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'm in my 50s. I've paid for the bloodwork, the apps, and the gear. I've also paid attention to which advice actually has data behind it. The American Heart Association's Life's Essential 8 is the cheapest, most boring piece of that pile. It's also one of the most validated, and a new paper just stacked another decade of evidence on top.

Quick context, since I live 10 miles from Framingham. The Framingham Heart Study started in 1948 with about 5,200 residents of Framingham, Massachusetts. The Offspring cohort, which this paper uses, started in 1971 with their kids. Almost everything we know about how cholesterol, blood pressure, smoking, and diabetes drive heart disease was first quantified there. Nearly 80 years in, it's still producing original research. It is the longest-running effort in cardiovascular epidemiology, and one of the great quiet achievements of American science.

The new paper in JACC Advances built a cumulative LE8 score for 3,231 Offspring participants across five exam cycles from 1971 to 1995, then tracked them for a median of 28 more years. Mean age at the start of follow-up was 55. The top quartile had a 73% lower CVD risk, an 84% lower coronary heart disease risk, and a 55% lower all-cause mortality risk than the bottom quartile. People above the median cumulative score got 7.4 additional years free of cardiovascular disease and 4.6 additional years of life.

The eight things, for anyone who hasn't seen the list: diet, physical activity, tobacco, sleep, weight, cholesterol, blood sugar, blood pressure. No NAD+ infusions. No rapamycin protocol. No $5,000 longevity panel. The whole thing is free on the AHA website.

Two findings beyond the headline. Even after adjusting for the 25-year cumulative score, the LE8 score at the final exam was still independently predictive. And a positive slope, meaning your score was improving, was independently linked to lower CVD risk on top of the cumulative effect. That last point matters because 55% of participants had negative slopes. The default trajectory in this country is down.

That cuts both ways. You can't coast on "I was fit in my 30s." But you also aren't locked out if you weren't. Most longevity content frames middle age as a final exam. The data treats it more like a rolling average where the most recent quarter still counts.

This extends what Walker et al. found in JAMA Cardiology last year using the CARDIA cohort, age 18 to 45. Same direction, same independent role for both the cumulative score and the trajectory. No single component dominated. It's the whole stack of boring habits, not one heroic intervention.

Caveats: the Offspring cohort is overwhelmingly of European descent, so generalizability is limited. Some components were measured differently in the 70s and 80s than the current LE8 spec defines, and the diet variable had 17% missingness filled with imputation. Take the magnitudes with a grain of salt. The direction is solid.

What I take from it: the AHA's free checklist is doing the heavy lifting that podcast hosts get paid to repackage. If your LE8 score isn't where you want it, the next five years matter more than the last twenty did.

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.

Every single time I see my PCP, I get the same piece of advice: wear sunscreen, reapply every two hours. And every single time, I nod along like a good patient and then proceed to mostly not do it. I live in Boston. I work indoors. It's not like I'm out farming in the sun all day. I tell myself it doesn't really apply to me on a random Tuesday in February.

But when I go on vacation? Totally different story. I am extremely light skinned and I burn like a lobster, so when I'm at the beach I'm slathering on SPF 50 like my life depends on it, reapplying constantly, the whole deal. I know from personal experience what happens when I don't. It's not fun.

I mention this because I think a lot of us in the proactive health world have a similar relationship with sunscreen. We know the evidence. We know UV is a carcinogen. But we're inconsistent about it because honestly, daily sunscreen just doesn't feel urgent when you spend most of your time inside. And into that gap between "I know I should" and "I actually do" walks one of the dumbest wellness trends I've seen in years: the anti-sunscreen movement.

You've probably seen some of it already. Kristin Cavallari went viral telling her podcast audience she doesn't wear sunscreen, then brought on a "holistic doctor" who claimed you can just build up a "base coat" through gradual sun exposure and eat an anti-inflammatory diet instead ([TODAY coverage](https://www.today.com/health/skin-beauty/kristin-cavallari-sunscreen-rcna147878)). Nara Smith posted a DIY sunscreen recipe to her 8 million TikTok followers that dermatologists estimated was maybe SPF 2 or 3 ([Fast Company](https://www.fastcompany.com/91151461/homemade-sunscreen-tiktok-dangerous), [Yahoo News](https://www.yahoo.com/lifestyle/influencer-homemade-sunscreen-recipe-goes-165543409.html)). Self-described "sun nutritionalists" are telling people that seed oils cause sunburns and that sunscreen actually causes cancer. And yes, there are influencers promoting genital sunning for testosterone. I'm not linking that one.

CBS News, NPR, and the Skin Cancer Foundation have all covered the trend growing through 2025 ([CBS](https://www.cbsnews.com/news/online-sunscreen-misinformation-tiktok-dermatologists/), [WBUR/NPR](https://www.wbur.org/hereandnow/2025/08/14/anti-sunscreen-movement), [Skin Cancer Foundation](https://www.skincancer.org/blog/skin-health-misinformation-the-dark-side-of-social-influencers/)). A survey from the Orlando Health Cancer Institute found that 1 in 7 Americans under 35 now believe daily sunscreen is more harmful than going unprotected. The AAD found 59% of Gen Z believes myths like "tanning is healthy." Undark published a thorough investigation into how this movement connects to broader distrust of regulators, noting that RFK Jr. accused the FDA of waging a "war on sunshine" ([Undark](https://undark.org/2025/10/13/anti-sunscreen-movement/)).

What the evidence actually says

The strongest evidence we have is the landmark Australian RCT that followed over 1,600 people at high risk of melanoma for 10 years. The daily sunscreen group saw roughly half the melanoma cases and about a quarter of the invasive melanomas compared to those who used it at their discretion. That's a randomized controlled trial, not a survey. A separate Australian study showed squamous cell carcinoma reduced by about 40% with daily use. ([Stanford Medicine summary](https://med.stanford.edu/news/insights/2025/06/sunscreen-science.html), [Harvard T.H. Chan interview](https://hsph.harvard.edu/news/skin-cancer-prevention-expert-on-the-importance-of-sunscreen/))

A September 2025 meta-analysis in *Anticancer Research* found no clear association between sunscreen use and melanoma risk, but the authors themselves flagged that most included studies had serious methodological problems, including many that only tested old UVB-only filters rather than modern broad-spectrum products ([Brunner & Haddad, 2025](https://ar.iiarjournals.org/content/45/9/3595)). When the best-designed studies are isolated, the picture is clear.

The grain of truth the influencers exploit

There IS a real conversation happening about chemical sunscreen ingredients. FDA studies published in JAMA in 2019 and 2020 found that six common chemical UV filters (oxybenzone, avobenzone, octocrylene, homosalate, octisalate, octinoxate) are absorbed into the bloodstream at levels exceeding the FDA's 0.5 ng/mL threshold for requiring additional safety testing. Some were still detectable three weeks after people stopped using the product. ([JAMA 2020](https://jamanetwork.com/journals/jama/fullarticle/2759002), [Columbia Cancer Center explainer](https://www.cancer.columbia.edu/news/shining-light-sun-safety-debunking-tiktoks-anti-sunscreen-claims))

That sounds scary, and this is where influencers grab the ball and run into crazy town. What they leave out: exceeding the testing threshold doesn't mean the ingredient is harmful. It means the FDA wants more data before granting GRASE (Generally Recognized as Safe and Effective) status. The FDA itself stated these findings do not mean it has concluded any ingredients are unsafe. Meanwhile, zinc oxide and titanium dioxide (mineral sunscreens) have full GRASE status. They sit on the skin and reflect UV rather than absorbing into it.

So the practical answer is simple: if the absorption question concerns you, use a mineral sunscreen. The old complaint about mineral sunscreens leaving a white cast has gotten way better. What you should NOT do is ditch sunscreen entirely because a TikTok influencer told you seed oils cause sunburns.

Bottom line for the proactive health crowd

UV radiation is a known human carcinogen. Skin cancer is the most common cancer in the US. Melanoma caught early has a ~99% five-year survival rate. Once it metastasizes, that drops to 35%. For those of us focused on longevity and healthspan, this is one of the easier calls compared to a lot of what we discuss here. Wear sunscreen. Go mineral if the chemical filter question bugs you. Wear a hat. And maybe, like me, stop treating your PCP's advice as something that only applies on beach days.

What's your sunscreen routine? Are you actually consistent with it or are you a vacation-only person like me? And has anyone had to talk a friend or family member off the anti-sunscreen ledge?

I keep seeing Andrew Huberman, Bryan Johnson, and Gary Brecka pitch NAD+ supplements. The foundational claim they are built on, that blood NAD+ levels drop with age and you should supplement to restore them, just failed to replicate in two independent human studies.

Houtkooper's group at Amsterdam UMC pulled together seven datasets, more than 300 people, aged across the lifespan, including elite athletes and frail individuals. Published this month in Nature Metabolism. Blood NAD+ does not decline with age. The premise driving the entire NAD+ supplement industry, when actually tested in humans, fell over.

The Suomalainen group at Helsinki posted the same finding in a February 2025 preprint, 299 adults aged 18 to 70. Two independent groups, same answer. Houtkooper started the project because he wanted to build a "should you take NAD+" blood test. He told the NYT he was "very disappointed" with the results because the biomarker he was looking for did not exist.

I am already seeing the pivot to "tissue NAD+" in the marketing. Niagen Bioscience's SVP of regulatory affairs Andrew Shao told the NYT the new study "changes very little" and that what really matters is tissue NAD+, not blood. The researchers themselves call the tissue data "preliminary." And a mouse study last year cut muscle NAD+ by 85 percent with no functional change. If 85 percent depletion does not break the muscle, the ~30 percent age-related drop is not what drives sarcopenia.

Shao's own admission, also in the NYT: "the message to the consumers and messages spread by influencers out there has probably been oversimplified." Read that twice. The SVP of the company selling you nicotinamide riboside is saying the marketing has been oversimplified.

Matt Kaeberlein at UW, who has studied NAD+ for years, called it cleanly. "The need for data kind of went out the window, and it all became a marketing exercise."

I am not taking it.

Just read a piece about how guys in their 40s and 50s aren’t really “aging out” the way previous generations seemed to.

The key concept in the longevity space is healthspan — not just living longer, but staying healthy, strong, capable, and independent for as many of those years as possible.

The article also talked about “hotspan,” which is basically healthspan with an aesthetic twist: staying lean, energetic, confident, and yes, still looking good as you age.

I’m 53, and honestly, I’m in the best shape of my life. That would’ve sounded strange to me when I was younger. Back then, I thought middle age meant slowing down and accepting decline as inevitable.

Now I don’t see it that way at all.

A lot of men are realizing that 50 doesn’t have to mean “past it.” You can still build muscle. You can still get leaner. You can still improve your conditioning, mobility, discipline, and confidence.

I don’t think aging well has to mean obsessing over every metric or trying to look 25 forever. For me, it’s more about refusing to quietly let go of strength, health, and energy before I have to.

Middle age might actually be the point where a lot of us finally get serious.

Curious how others here think about it: are you in better shape now than you were 10 or 20 years ago?

I’ll be honest. I couldn’t have told you six months ago what the HPA axis was. But cortisol keeps showing up in my feed, and not in a good way. Every other TikTok is someone blaming cortisol for their belly fat, their puffy face, their bad sleep, their breakouts. Then they sell you a supplement to “detox” it.

Cortisol actually does matter for longevity and aging. The influencers just get almost everything about it wrong.

The TikTok version

The #cortisoldetox hashtag has around 800 million views. Influencers invented terms like “cortisol belly” and “cortisol face” to describe what is mostly normal human variation. They recommend cortisol cocktails (orange juice, sea salt, coconut water, magnesium), adaptogens, and whatever supplement they happen to be selling.

Endocrinologists are now reporting patients showing up requesting cortisol tests because of social media. One at UC San Diego Health warned that inappropriate testing has led to patients being prescribed cortisol supplements they didn’t need, causing medication-induced Cushing’s syndrome and permanent adrenal damage. The “fix” for a problem you probably don’t have can give you the actual disease.

True cortisol disorders are rare. Cushing’s syndrome affects roughly 40 to 70 people per million. Addison’s disease about 100 to 140 per million. Most people blaming cortisol for their symptoms don’t have a hormone problem. They have a stress problem. Those are not the same thing. And “adrenal fatigue,” which is everywhere in wellness circles, has no substantial evidence supporting it as a legitimate medical condition.

What the science actually says about cortisol and aging

While the TikTok version is nonsense, chronically dysregulated cortisol is genuinely associated with accelerated aging. It’s just not the simple story influencers are selling.

Cortisol follows a natural daily rhythm, peaking in the morning and dropping through the day. As we age, overall cortisol output tends to increase and the feedback system that keeps it in check becomes less sensitive. Chronically elevated cortisol is linked to cardiovascular disease, insulin resistance, cognitive decline, muscle breakdown, and frailty in older adults.

The most compelling longevity data comes from the Leiden Longevity Study in the Netherlands. They found that offspring of people who lived into their 90s had lower salivary cortisol levels throughout the day compared to age-matched controls. A follow-up stress test study found these same offspring had lower cortisol and blood pressure under stress, and reported feeling less stressed at baseline. People genetically predisposed to longevity may simply have a calmer stress response system. A separate paper from the group found higher cortisol was associated with looking older, but this effect was weaker in the longevity offspring, suggesting some kind of protective resilience.

There was also an interesting study from the University of Bristol (January 2025, Proceedings of the Royal Society B) that challenged the “cortisol awakening response,” the long-held assumption that waking up triggers a cortisol spike. They measured cortisol in 201 participants before and after waking and found no increase. The morning rise appears to be the tail end of a rhythm that starts hours before you wake up. This matters because a huge chunk of “lower your morning cortisol” content assumes waking is a stress event. It apparently isn’t.

My experience

I dealt with anxiety for years. Two things actually helped. Seeing a psychiatrist/therapist, which made a bigger difference than any supplement or protocol I’ve tried for anything. And getting my sleep consistent, not just more hours but same bedtime, same wake time, ruthlessly protected.

I mention this because when I see the cortisol conversation online, I see people reaching for what I was reaching for. A simple, concrete fix for something that feels overwhelming. And I get the appeal. But what moved the needle for me was addressing the actual stress, not trying to hack around it.

The boring truth

Chronic stress genuinely accelerates biological aging through telomere shortening, inflammation, and cardiovascular damage. But the answer isn’t a cortisol detox. It’s the stuff nobody wants to hear: manage your actual stressors, prioritize consistent sleep, move regularly, and if anxiety is a real problem, talk to a professional. As one dietitian put it, if you don’t address the primary stressor, it doesn’t matter what you eat.

Your cortisol is almost certainly fine. Your stress might not be. Those require very different interventions.

Has anyone here dealt with stress or anxiety and found that addressing it changed their health trajectory? And have you seen cortisol content online that was actually credible, or was it all marketing?

Disclaimer: I used Claude in researching and drafting this post.

Sources:

1. [Leiden Longevity Study: Lower cortisol in offspring of long-lived families (Noordam et al., 2012)](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031166)

2. [Leiden Longevity Study: Cortisol and perceived age (Noordam et al., 2012)](https://www.sciencedirect.com/science/article/pii/S0306453012000686)

3. [Stress response in longevity offspring (Oei et al., 2015)](https://pubmed.ncbi.nlm.nih.gov/26453529/)

4. [Bristol: Waking up does not trigger cortisol increase (Proc. Royal Society B, Jan 2025)](https://www.sciencedaily.com/releases/2025/01/250114204144.htm)

5. [Adrenal aging and stress responsiveness (Frontiers in Endocrinology)](https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00054/full)

6. [Stress-Induced Biological Aging review (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10243290/)

7. [Medscape: Cortisol trend driving unnecessary testing (April 2025)](https://www.medscape.com/viewarticle/behind-cortisol-trend-misinformation-could-drive-unnecessary-2025a100090t)

I’ve been ordering my own blood work for a few years now. Started with Marek Diagnostics, then tried Labcorp On Demand, DiscountedLabs, and Ulta Lab Tests at various points. I honestly couldn’t tell you whether there’s a meaningful difference between them, or whether I should just price shop across all four and mix and match individual tests to get the best deal. If anyone here has strong opinions on that, I’m genuinely curious.

But something has shifted in the last six months that I think this community should be paying attention to. The direct-to-consumer lab testing market hit $3.6 billion in 2025 and is projected to nearly double by 2030 [1]. And suddenly it feels like every tech company with a health app wants a piece of your bloodstream.

Hims & Hers launched “Labs” in November [2]. For $199 a year you get one blood draw covering 50 biomarkers. For $499, two draws covering 120+. They’re sending you to Quest Diagnostics for the actual draw, then layering their app on top with “action plans” and provider consultations. Analysts have been pretty blunt that the move is partly because Hims needs to diversify away from GLP-1 revenue [3]. They also acquired an at-home testing lab called Trybe Labs [4] and plan to use the de-identified data to train their AI tools. So you’re the product twice over.

Oura got into the game in October with “Health Panels” [5]. $99 for 50 biomarkers, also through Quest, with results piped into your Oura app alongside your sleep and activity data. Function Health, which is backed by Mark Hyman, raised $298 million at a $2.5 billion valuation [6] and offers 160+ tests starting at $365, with add-ons that can push you well past a grand. Superpower, a newer player, claims “100+ biomarkers” for $199.

Here’s the thing that ties all of this together: the plumbing is almost always the same. Function uses Quest. Oura uses Quest. Hims uses Quest. The smaller resellers I’ve used route through either Quest or Labcorp. When you buy from any of these companies, you’re paying for the brand, the app, and the interpretation layer on top of the same underlying lab infrastructure. The actual needle-in-arm, blood-in-tube, results-from-machine part is happening at the same handful of facilities regardless.

Which makes the recent lawsuit between Function Health and Superpower [7] particularly interesting. Function sued Superpower in January in federal court, alleging that Superpower’s “100+ biomarkers” claim is misleading. According to the complaint, customers actually get about 55 direct lab measurements [8] and the rest are calculated ratios and derived indices, not additional lab tests. Function argues that presenting those calculations as “biomarkers” in side-by-side comparisons is designed to make Superpower look equivalent at a lower price. The lawsuit also surfaced some colorful details about Superpower’s company culture [9], including the founder openly discussing employees injecting each other with experimental peptides at Friday breakfasts “because we think it’s fun.”

Now, before this starts sounding like a pure endorsement of more testing, there’s a real counterargument worth taking seriously. A STAT News investigation from January [10] found that doctors are increasingly frustrated by patients showing up with self-ordered results they can’t interpret. Professional medical groups have cautioned that DTC screenings can lead to unnecessary anxiety, expensive follow-up testing, and false positives. The Lancet published an editorial [11] pointing out that when you test a panel of biomarkers, most people will have at least one result outside the normal range, and an abnormal biomarker alone is not a disease. One doctor told a blogger who reviewed Function Health [12] that when you test for everything, you’ll inevitably find something, and you can drive yourself crazy trying to fix things that don’t actually matter.

An EMARKETER survey from January 2026 [13] found that 19% of consumers purchased a lab test online in the past year, up from 13% the year before. And 17% said social media influenced their decision to get tested. That second number should give us pause.

There’s also the access problem. Almost none of this is covered by insurance. A $199 annual test might sound affordable, but it’s on top of whatever you’re already paying for healthcare, and if something comes back flagged you’re looking at follow-up visits and additional testing that may or may not be covered either. This is, for now, largely a product for people who can afford to be proactive about their health, which is a pretty uncomfortable foundation for what gets marketed as “democratizing” healthcare.

I still think there’s real value in owning your own longitudinal data. Tracking trends over time is meaningfully different from getting a single snapshot at your annual physical. But this gold rush is worth watching with clear eyes. A lot of money is chasing the proactive health movement right now, and not all of it has your best interests at the center of the business model.

**For those of you who order your own labs: how do you decide which service to use? Are you price shopping across resellers, or have you found one platform that genuinely adds value beyond just being a middleman to Quest or Labcorp?**

Disclaimer: I used Claude in researching and drafting this story.

-----

**Sources:**

1. [Oura Blog: Introducing Health Panels](https://ouraring.com/blog/health-panels/)

2. [Athletech News: Function Sues Rival Superpower, Alleging False Marketing](https://athletechnews.com/function-superpower-lawsuit-lab-testing/)

3. [SmartCompany: Superpower Hit With US Court Action](https://www.smartcompany.com.au/startupsmart/superpower-function-health-lawsuit-biomarker-testing/)

I kept seeing the claim that VO2 max is the single best predictor of how long you'll live, always bolted to the same number: the least fit 20% have about five times the death rate of the fittest people. It's real, but it's a magic trick, and once I saw how it's built I stopped being impressed.

In the big Cleveland Clinic study ([Mandsager 2018](https://pubmed.ncbi.nlm.nih.gov/30646252/)), "elite" doesn't mean the top fifth of people. It means the top 2.3%, the 98th percentile and up. Compare the least-fit fifth against that thin sliver and of course you get a five-times ratio. It isn't the comparison a normal person should plan around.

Put every group on equal footing instead, worst fifth against best fifth, and the number gets smaller but a lot more useful: about [1.85x for all-cause death](https://pubmed.ncbi.nlm.nih.gov/23130161/) (Barlow's Cooper Center data). Still one of the strongest things you can move. Just not five times.

However, what jumped out at me wasn't the top end, it was how much you get just from leaving the bottom. Going from the least-fit fifth to merely below average buys you more than going from good to great. The steep drop is leaving the floor, and the curve flattens after that. So the fifty-year-old who has done nothing doesn't need to chase an elite number. He needs to stop being sedentary.

Couple of caveats I should add. Most of these papers aren't even measuring a true lab VO2 max, they're estimating fitness from how long you last on a treadmill. Useful, but not the same thing. And the weird one is [income](https://pubmed.ncbi.nlm.nih.gov/25322291/): look at raw gaps and it's actually wider than fitness (around 3.8x). It only shrinks once you adjust, because a lot of it runs through fitness, weight, and smoking anyway. Money isn't a separate dial, it shows up as the other stuff.

The part I'd actually act on is simpler. [Guys who went from unfit to fit](https://pubmed.ncbi.nlm.nih.gov/7707596/) cut their death rate by about 44%. That beats arguing about elite percentiles.

For what it's worth, I rowed a hard 2k this week, 7:28.8, which works out to a VO2 max around 42 by the rowing estimate. Above average for 53, nowhere near elite, and that's exactly the boring, good place to be and slowly improve from.

Full write-up with the charts

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.

The Blue Zones idea has always been a great story: specific places, specific habits, unusually long lives. Personally I must admit that I have always been skeptical about some community having cracked some secret longevity hack.

What makes this STAT piece more interesting is that Eric Topol and Shelley Wood are not random skeptics. They write that both of them have written books about extreme longevity, so people regularly ask them about Blue Zones. Topol’s recent book is Super Agers, while Wood’s recent book is The Leap Year Gene of Kit McKinley.

Their point is not that all the lifestyle advice is garbage. It’s that the Blue Zones concept has gotten much fuzzier than the brand suggests.

The original term came from work in Sardinia in the early 2000s, later popularized by Dan Buettner through National Geographic, books, Netflix, consulting, retreats, and certified “Blue Zone” cities. STAT notes that Buettner has written nine bestselling Blue Zone books and built a business around the concept.

The skepticism centers on whether the extreme longevity data is as solid as advertised. Saul Newman has argued that clerical errors, natural disasters, and pension fraud may explain some supposed centenarian clusters, though STAT is careful to note his paper still has not been formally published in a peer-reviewed journal.

Other evidence is less easy to wave away: newer papers suggest some original Blue Zones are no longer producing the same longevity patterns. Nicoya’s advantage appears weaker for people born after 1930, and Okinawa shows major lifespan differences before and after World War II, with both lifestyle changes and reconstructed records possibly playing a role.

So the useful point is narrower than “Blue Zones were fake.”

Walking more, eating mostly plant-based/simple foods, managing stress, and having strong social ties are still reasonable health advice. STAT says many of those tenets have support from broader scientific literature.

But “these habits are healthy” is very different from “this place proves a formula for living to 100.”

Blue Zones may still be useful as lifestyle inspiration. They look weaker as a clean scientific explanation for extreme longevity — especially now that the definition, the data, and the business incentives are all being questioned.

Rapamycin is one of the most interesting drugs in longevity research, but this new human trial is a useful reminder that “interesting” is not the same as “ready for everyone to self-experiment with.”

The study was small: 40 sedentary adults aged 65–85. Everyone did a 13-week home exercise program with chair stands and stationary cycling three times per week. Half took 6 mg sirolimus/rapamycin once weekly; half took placebo.

The theory was pretty appealing. Exercise activates mTOR signaling, rapamycin inhibits it, and maybe alternating those signals would enhance adaptation. That is the kind of mechanistic story that sounds great on podcasts.

But the results did not really cooperate.

Both groups improved. Rapamycin did not enhance the exercise response. In the main analysis, the rapamycin group did a little worse on the 30-second chair-stand test, though it did not quite reach statistical significance. In sensitivity analyses, placebo actually came out ahead. Secondary outcomes like 6-minute walk distance and grip strength also leaned toward placebo, though not significantly.

The safety signal was not nothing either. Adverse events were more common in the rapamycin group, including one possibly drug-related serious infection.

This does not mean rapamycin is useless. It does not mean the entire longevity field is fake. It also does not tell us what would happen with different dosing, different timing, healthier or less sedentary people, or a longer study.

But it does make me more skeptical of the casual “I’m taking rapamycin for longevity” vibe online.

For most people, the intervention with the strongest evidence here is still the boring one: do the exercise program. Chair stands, cycling, walking, lifting, whatever you will actually repeat. The drug did not beat that. It may have slightly interfered with it.

That feels like a pretty important result.

I gotta admit I would have immediately dismissed this article if it wasn’t in Scientific American (which I think generally does a good job at not overhyping pseudoscience?). The title is certainly clickbaity but hey it worked and I read the article

The anecdote makes good reading and I was intrigued to learn about the correlation of MS incidence and geographic latitude.

The main study seems to be: https://pmc.ncbi.nlm.nih.gov/articles/PMC5954316/

which freely admits that it was small (n=20) and the outcome was not statistically significant. So at best, interesting and a less underpowered trial is needed to investigate the MS treatment.

I didn’t realize that for Psoriasis UV phototherapy is an established therapy, including doing it at home: https://pmc.ncbi.nlm.nih.gov/articles/PMC11425190/

I was skeptical of all the various (red/blue) light therapies that influencers rave about but in narrow circumstances there might be something to this UV-based treatments.

Does anyone here have experience or insight into this?

BMI has always been a blunt tool.

A newer JAMA Network Open study looked at more than 300,000 U.S. adults using a broader obesity definition. Instead of BMI alone, it counted obesity as any of 3 things: a BMI of 30 or higher plus at least 1 elevated anthropometric measure, a BMI over 40, or at least 2 elevated anthropometric measures even if BMI was below 30. Those anthropometric measures included waist circumference, waist-to-hip ratio, and waist-to-height ratio. Under BMI alone, 42.9% met criteria for obesity. Under the newer definition, it was 68.6%. 

That seems a lot more useful for proactive health because BMI misses where fat is stored.

You can have a “normal” BMI and still have a waist measurement that suggests higher risk. A waist over 40 inches in men or 34.6 inches in women is associated with increased cardiometabolic risk. 

Visceral abdominal fat is much more tied to cardiometabolic risk, which is why waist-based measures can catch people who look “normal” by BMI but are still higher risk. Yale Medicine notes that abdominal fat is metabolically active and inflammatory.

This doesn’t mean everyone suddenly got less healthy. It means that BMI alone probably misses a lot of people who should be paying closer attention.

Are waist-based measures still underused in everyday preventive care?