u/DadStrengthDaily

I inject Zepbound every week, so I understand the retatrutide FOMO. Reta is Eli Lilly's triple agonist, the next molecule up from tirzepatide, still in Phase 3 trials and approved nowhere in the world. That is what got me looking at where people actually buy it.

Sam Sulek, one of the biggest fitness YouTubers, says on camera that he co-owns a peptide company called NewBioRx. The storefront sold a $285 pre-filled retatrutide pen under the standard research-chemical disclaimer: "Bodily introduction of any kind into humans or animals is strictly prohibited by law." A second website carrying the NewBioRx logo published a milligrams-to-units conversion table for that pen and a twelve-photo walkthrough titled "How To Give Yourself a Shot." One site swore no human may ever use the product. The other assumed a human was using it.

The timing matters. On August 12, Eli Lilly sued six US sellers of retatrutide, and its complaints lean on exactly this kind of material, the dosing calculators and injection guides, as evidence that a "research use only" label is a fiction. NewBioRx is not one of the six defendants, and nobody has sued Sulek's company. It is the same pattern, though. The FDA has separately said retatrutide cannot legally be used in compounding at all.

Then, on Sunday afternoon, while I was finishing the write-up, the pen's product page went 404 and the entire instructions site was replaced by a NewBioRx-branded "Coming soon" page. The 16 mg and 30 mg vials are still for sale. I don't know who took the pages down or why. I had archived everything first, and the write-up links to the archives.

I documented the whole paper trail, the product pages, the instructions site, the corporate filings, and Sulek's own on-camera explanation that research-only products are not "held to the same quality standards" as FDA-regulated ones, with screenshots: full write-up on my blog with the details.

The disclaimer itself is what bothers me most. It does not describe the product, and the seller's own instructions contradicted it. Its practical effect is that when something goes wrong, the person holding the pen owns the outcome, not the company that sold it. I think that is the real product being sold: deniability. Curious whether anyone here reads "research use only" differently.

On Aug 12 Lilly filed six lawsuits against US sellers of reta (Astra, Legendary, Texas and Lone Star Peptides, plus a med-spa and a compounding pharmacy), referred 200+ sellers to the FDA/DOJ, and flagged 14,000+ listings.

The part that actually hits supply: Lilly is also pressuring the payment processors, card companies and shippers these sellers use. This market already struggles to keep a card processor (why so much runs on crypto/PayPal), so that squeeze may bite harder than the suits.

Two things worth knowing: the enforcement is aimed at sellers, not buyers. And because reta isn’t approved anywhere yet, there’s no legitimate version to check a vial against, so dose and sterility stay unverifiable no matter what COA comes with it.

Not moralizing (I’m on compounded meds myself). Fuller writeup with full complaints if useful: https://dadstrengthdaily.com/is-retatrutide-legal-to-buy/

I heard about this on Peter Attia's episode with Jim Otvos, the chemist who invented NMR lipoprotein testing. Most of it was about a marker I had never come across, so I went and read the papers afterwards.

It is called MVX. The same scan that gives you a standard lipid panel also measures six other things, and those get combined into an inflammation score, a malnutrition score, and one number sitting on top. Every other marker I track names a disease. ApoB points at atherosclerosis, Lp(a) tells me what I inherited. MVX just tells you how likely you are to die of anything.

The catch is the size of it. Comparing the worst-scoring group to the best, the hazard ratio for death is 8.01 among cardiac catheterisation patients and 1.21 in a general-population cohort of 274,092. Those are group comparisons, not your personal odds. The association shrinks the further the study group gets from a hospital, and that is the part that decided it for me.

Nobody has run a trial of any kind showing you can move the number on purpose. That has not stopped the lab's own white paper from suggesting detoxification strategies for a bad score.

I am not ordering it. GlycA, the inflammation input, is steadier than the hs-CRP I use now, and you can order that one by itself for $32.

Full write-up, with every paper linked: https://dadstrengthdaily.com/mvx-test-metabolic-vulnerability-index/?utm\_source=reddit&utm\_medium=social&utm\_campaign=mvx-proactivehealth

I posted the STAT investigation here back in May. I finally went through the underlying papers myself, and the part that surprised me was not the criticism. It was that the two men who found the original Blue Zone no longer describe it the same way.

Michel Poulain, the demographer who co-coined the term, has asked twice in print for validation that has not been completed. His 2011 Okinawa paper is literally titled "A plea for in-depth validation," and he repeated the plea in 2024. Giovanni Pes, his co-author on the original Sardinian work, wrote in a 2025 rebuttal that the ages have "been extensively validated." Same finding, fifteen years apart, and the founders land in different places.

The science holds up better than the critics say. An independent 2025 review of 65 records graded Ogliastra, Okinawa and Nicoya "well-characterized," and Sardinia has the strongest documentation of the lot. The same review excluded Loma Linda outright: no epidemiological studies, just Buettner's own narratives. Which fits how it got in. Buettner told the New York Times his National Geographic editor said "you need to find America's blue zone," and told Science "I never bothered to delist it."

The business side bothers me more. Keeping the certification runs a city about $100,000 a year. Fifteen Iowa communities signed up, ten of them under an insurer sponsorship. When that ended, Cedar Rapids, Iowa City and Marion left. Cedar Rapids asked what renewal would cost and was told the fee was "considered proprietary information." I could not find any peer-reviewed evidence that one of these projects has added a year to anyone's measured lifespan.

Buettner himself said on Rich Roll's podcast that Okinawa is now "the least healthy prefecture in all of Japan." The Blue Zones website still tells visitors that women there live longer than any women on the planet.

My honest read: some of these clusters were real, the evidence varies enormously from one to the next, several of the advantages have since gone, and none of it establishes that nine lifestyle rules caused anything. The full write-up, with the records and the money, is here (https://dadstrengthdaily.com/are-blue-zones-real/?utm\_source=reddit&utm\_medium=post&utm\_campaign=are-blue-zones-real).

Has anyone here spent real time in one of the five? I am curious whether the day-to-day looks anything like what gets sold.

Last October this sub had a well-received thread arguing that hs-CRP now matters as much as LDL, on the strength of the ACC writeup showing it predicts events as well as or better than cholesterol in people already on statins. That prediction claim is solid. Ridker's 2023 analysis of three statin trials found the same thing, and in the Women's Health Study the top-versus-bottom quintile hazard ratio was 1.70 for hs-CRP against 1.35 for LDL-C.

Friday we got the other half of that question.

Novo Nordisk reported ZEUS. Ziltivekimab blocks interleukin-6, which is the signal hs-CRP is downstream of, so this is about as direct a test of "treat the inflammation" as anyone has run. They enrolled 6,376 people with atherosclerotic disease, chronic kidney disease and hs-CRP of 2 or above. Median hs-CRP at entry was 4.5. Their cholesterol was already handled: 88 percent were on a statin, average LDL 77.7.

The drug worked on the biology. IL-6 and hs-CRP both fell. Hazard ratio for heart attack, stroke or cardiovascular death was 0.99, with the range running 0.88 to 1.11. There were more serious infections, which follows from blocking IL-6.

This does not mean inflammation is irrelevant. Colchicine cut events in COLCOT and LoDoCo2, though CLEAR SYNERGY was flat in 2024.

CANTOS is the one that bothers me most, because you cannot blame the population for it. Same trial, same patients, one drug at three doses. hs-CRP fell 26, 37 and 41 percentage points versus placebo, neatly in order. The events did not follow that order at all. The 150 mg dose squeaked past its prespecified bar at 0.021 against a limit of 0.02115, and the 300 mg dose that suppressed hs-CRP hardest missed its bar and counts as a failure.

Which puts JUPITER in a different light for me. It selected 17,802 people on hs-CRP of 2 or above and halved their events, but the drug was rosuvastatin, and it cut their LDL by 50 percent while it cut their hs-CRP by 37. The 2026 ACC/AHA guideline reads that trial as producing a benefit "with an effect size compatible with the LDL-C-lowering effect of statins alone."

So hs-CRP looks like a good way to spot who is in trouble. Nobody has shown yet that lowering it is what gets them out. The guideline treats it that way too, listing it as a risk enhancer at 2 mg/L or above on more than one occasion, where its job is to help confirm you belong on a statin.

Has a high hs-CRP ever changed what your doctor actually did, beyond the statin conversation?

Back in April I posted the Scientific American piece about drugs that calm inflammation, and I hedged in the comments. I said inflammation gets blamed for basically everything in health and I did not think it meant anyone should start chasing anti-inflammatory drugs or biomarkers.

Last Friday Novo Nordisk reported ZEUS, which was built to answer exactly that. Ziltivekimab blocks interleukin-6, the signal your hs-CRP is downstream of. They gave it to 6,376 people with heart disease, kidney disease and an hs-CRP of 2 or above. The drug did its job on the biology, dropping both IL-6 and hs-CRP. Hazard ratio for heart attack, stroke or cardiovascular death: 0.99, range 0.88 to 1.11.

I want to be careful, because this is not "inflammation doesn't matter." Colchicine cut events in COLCOT and LoDoCo2, and canakinumab cut them in CANTOS.

CANTOS is the part that actually changed my mind, though. Same trial, same patients, one drug at three doses, and hs-CRP fell 26, 37 and 41 percentage points more than placebo, neatly in order. If the number were the thing, the biggest drop should have bought the most protection. It didn't. The middle dose scraped past its statistical bar at 0.021 against a limit of 0.02115, and the top dose, the one that crushed hs-CRP hardest, missed its bar entirely.

Meanwhile the one trial that took people picked out by a high hs-CRP and genuinely changed what happened to them was JUPITER, which cut events roughly in half using rosuvastatin. A cholesterol drug. The current ACC/AHA guideline says that trial's benefit came "with an effect size compatible with the LDL-C-lowering effect of statins alone."

So my read now is that hs-CRP is very good at spotting who is heading for a heart attack, and nobody has shown that lowering it is what helps them. The guideline seems to use it that way too: a reading of 2 or above, on more than one occasion, helps confirm someone belongs on a statin.

My own went 2.83 to under 0.2 over a year, and I used to be quietly proud of that. However, my LDL went 110 to 56 and my ApoB 95 to 59 across the same stretch, and I am on tirzepatide, which lowers hs-CRP by itself. Four numbers moved and I had been giving the credit to the one I found most interesting. I wrote the whole thing up here, charts and all.

If your hs-CRP came back at 2.5, does that change anything you actually do?

I wrote here in June about a friend of mine who has been sober for years and still gets the cravings. He does everything the program asks and the wanting never fully switches off. A month before that he started the Wegovy pill hoping the thing that quiets food noise might quiet the other kind. Since then it mostly has. That is one guy with no control group, so it proves nothing, but it is why I read the trial news last week as closely as I did.

Two trials reported a day apart and they did not agree with each other. That same week the VA opened a Phase 3 built on the exact number they did not agree about.

The oral semaglutide trial published July 29. Fifty people, eight weeks, and it missed its primary endpoint badly. That endpoint was a single booze craving question asked in a lab after you hold and smell your drink, p=0.68. Plenty of secondaries moved, including heavy drinking days, but the authors ran about ten tests without correcting for it and call the study exploratory themselves. A conservative correction would wipe out all of it.

The day before, Altimmune reported topline results for pemvidutide, which hits the glucagon receptor as well as GLP-1. That one ran twenty four weeks in a hundred people, and it hit its primary on heavy drinking days. It also moved a blood marker of alcohol intake, which matters because everything else in both trials is self-reported. It is a press release though, not a paper, and nine of the hundred participants are missing from the denominators with no explanation of how they were handled.

https://preview.redd.it/lgtlapy0vsgh1.png?width=1080&format=png&auto=webp&s=f06fe5f3c8d472f05862e76552b433346a6bf165

Here is the part I did not know. The endpoint the VA picked for CRAVE, its 622-veteran Phase 3, is a two level drop in WHO risk drinking level. For a man that can mean going from more than seven drinks a day to three or four. It is a real change and you can reach it without ever quitting. The FDA formally qualified that endpoint back in February 2025, so this is not a drug company moving the goalposts, and the FDA offers it alongside abstinence rather than instead of it. Still, the trial that everyone will quote in 2028 is measuring drinking less.

I am not sure how I feel about that. I would not call three drinks a day recovery. But of the roughly 28 million Americans with alcohol use disorder, about 7.6 percent got any treatment at all last year, and for the other 26 million nothing reached them.

All three of these trials enroll people who are currently drinking and measure whether they drink less. My friend is not drinking. Nothing being run right now is built for the guy who already stopped and still wants it.

I went through all of it properly with the numbers and two charts over here.

If you are already sober and on a GLP-1 for weight or diabetes, has it changed the wanting for you at all? That is the group nobody is studying and I would genuinely like to know.

Retatrutide just posted its fifth positive Phase 3 — up to ~23% body-weight loss in people who already have cardiovascular disease — and Lilly says it'll file for approval in Q1 2027 as a biologic.

That one word decides what you'll eventually pay. Zepbound, the drug in my fridge, gets 5 years of exclusivity before generics can arrive and drop the price ~85%. A biologic gets 12 years. Copies cost $100–300M to build and come down only 5–25%, and it can't be legally compounded even in a shortage — which is how a lot of people actually got tirzepatide the last three years.

Right now the FDA classifies retatrutide as a drug, not a biologic. The line comes down to counting amino acids: it lands one residue short, depending on whether a non-standard one counts. Lilly is in court trying to move it over. If it wins, the strongest obesity drug we've seen stays expensive far longer, with no cheaper version legal in the meantime.

None of this is about whether the drug works. 23% in people with heart disease is a real number. It's about who's ever allowed to sell you a cheaper copy, and that's being settled by an argument over how to count to 41.

I take tirzepatide and own Lilly stock, so the patient-friendly outcome cuts against my own portfolio.

My full breakdown

Today is the long awaited FDA committee vote on peptides. This is an important event but also quite weird in many ways. For one the indications cited in are not at all what people actually use these peptides for in the wild. I don’t know anyone pinning BPC-157 for ulcerative colitis?!

There have also been a number of shenanigans with the composition of the committee. Various members were accused of ties to the peptide industry (what Bloomberg describes as the “gold rush”). Other voting-only members were hastily added in the last few days.

If you want to watch it yourself, the FDA is streaming both days on YouTube free, starting at 8 a.m. Eastern on Thursday the 23rd and again on Friday the 24th. Thursday is the day that matters most if you only watch one, since that is when BPC-157 and TB-500 come up. The agency pushed Thursday’s end time back from 4:30 to 6:20 in the evening, which tells you something about how much public comment it is bracing for. One quirk of the schedule: the public gets to speak before the FDA’s scientists present, so the panel hears the advocates first and its own reviewers second.

I expect the meeting to have a C-Span boringness to it but tonight there will likely more peptide hype than ever.