Longevity Digest, October 11–18: what Peter Attia no longer takes, and a phase 3 failure for NAD boosters
In the week of October 11–18, 2026: Peter Attia revisits eight years of his own positions, a phase 3 trial finds an NAD precursor left early Parkinson's symptoms slightly worse, Blueprint publishes a complete training week, and Sinclair reports OSK data from rats with liver disease.
This digest covers the public output of Peter Attia, David Sinclair, Bryan Johnson's Blueprint team, and Rhonda Patrick between October 11 and October 18, 2026, Pacific Time. Peter Attia used his 400th episode to revisit positions he has held for years, and the list includes metformin for longevity and heavy barbell lifts. The same week brought a phase 3 test of an NAD precursor in Parkinson's, and the trial came back negative. Blueprint published a full training week, and David Sinclair described a second reprogramming program aimed at the liver.
The week in one screen
| Figure | Focus this week | Primary evidence tier | Actionable takeaway |
|---|---|---|---|
| Peter Attia | An AMA revisiting eight years of positions, plus a premium article on gray-market peptides' patent history 12 | A clinician's reflection episode; a review of 25 compounds whose findings sit behind a paywall | He no longer takes metformin for longevity, has grown more uncertain about rapamycin, and has moved off heavy squats and deadlifts; the free page gives conclusions, the reasoning sits in members' notes 1 |
| Bryan Johnson / Blueprint | A seven-day training template, written in the first person 3 | Company blog built on population studies and standard programming | At least 150 minutes of zone 2, 75 minutes of hard cardio, and two or three strength sessions a week 3 |
| Rhonda Patrick | Berberine's lipid numbers; a failed phase 3 trial of nicotinamide riboside in Parkinson's 45 | A meta-analysis of 14 placebo-controlled trials; a 410-person phase 3 trial | Berberine lowered LDL by about 18 mg/dL on average; nicotinamide riboside at 500 mg twice daily for a year did not help 45 |
| David Sinclair | OSK in rats with liver disease and a new ER-300 program; an NMN bone study in mice 67 | Company-reported preclinical data; a mouse study combining two drugs | OSK beat OSKM on survival and fibrosis in rats; the NMN result cannot be separated from the STING inhibitor it was given with 8 |
Peter Attia: a protocol he has revised
Peter Attia is a physician, the founder of the Early Medical practice, and the host of The Peter Attia Drive. He released two things in the window: episode #411, an Ask Me Anything recorded at the podcast's 400-episode mark and released on October 12, and a premium article on October 17 12.
The keto diet still works; his explanation changed
For three years Attia ate a ketogenic diet, and he calls that stretch "probably the best I ever felt" 9. His average morning beta-hydroxybutyrate, the ketone the diet raises, ran between 1.8 and 2.0 millimoles per liter 9. He stopped because he was tired of eating that restrictively, and he still describes the diet as effective 9.
What changed is his account of why it works. He once credited insulin suppression; today he thinks a ketogenic diet works the way other restrictive diets do, by making energy intake easier to control 9. His illustration is a person in ketosis who is gaining weight: low insulin on its own left the problem in place 9.
The practical consequence is less dogmatism about tactics. Attia says he has no strong preference among low-carb, low-fat, and mostly pescetarian approaches once a few principles are met, and he names one of them: "at a minimum, I want them hitting 1.4 grams per kilogram" of body weight 9.
Extended fasting, and how autophagy actually behaves
Attia spent about three years fasting on a schedule: seven to ten days once a quarter, plus a three-day fast in each of the other two months 9. He was chasing autophagy, the process by which cells break down and recycle their own damaged components 9.
The detail that changed his mind is measurement. Ketosis has a threshold he can read on a meter, roughly 0.5 to 1 millimole of beta-hydroxybutyrate; autophagy has no equivalent unit, and it ramps up gradually instead of switching on 9. From the preclinical literature and conversations with researchers, three days looked like the point where fasting goes beyond what exercise produces 9.
His summary of why he stopped is one line in the public preview: "the evidence, but also the cost" 9. The full episode and its show notes sit behind the membership paywall, so the accounting behind that sentence stays with the source 1.
The positions he says he has revised
The episode page lists the rest with timestamps, as conclusions waiting on members' notes to explain them 1. Metformin comes first. The page says Attia explains "why he no longer takes metformin for longevity" and why he no longer views it as geroprotective for metabolically healthy people 1. The ground has been shifting for months: a July article he co-wrote reviewed metformin's cancer-prevention case and found no benefit in the MAST trial, and this episode applies a similar test to longevity use 10.
Rapamycin gets a similar treatment: compelling animal data, unresolved human dosing, and what the page calls Peter's "growing uncertainty" 1. On cancer screening, he describes declining whole-body MRI quality and a shift toward more targeted alternatives, and he argues that early-stage detection is what matters while calling liquid biopsy technology "fuzzy" 1.
Exercise carries the largest revision. He describes the limitations of the 80/20 Zone 2 framework, programming cardio at lower training volumes, and a move away from heavy barbell squats and deadlifts toward deliberate management of injury risk 1. The frame for all of it is his own description of how good scientists work: "not married to a particular thesis being right," but "married to getting things as right as possible and reducing uncertainty by following the data" 1.
A second release, on where gray-market peptides come from
Attia's team also published a premium article on October 17, and only its opening is public 2. It takes on one argument used to explain why so many peptides lack clinical trials: that peptides are hard to patent, so pharmaceutical companies have no incentive to fund the studies 2.
The team says it traced the patent and development histories of 25 gray-market compounds, including BPC-157, TB-500, GLP-1 agonists, growth hormone secretagogues, and melanocortin peptides 2. The opening states the conclusion, that the ties to the pharmaceutical industry run deeper than the compounds' reputations suggest, and puts the compound-by-compound evidence behind the paywall 2. A reader can see the claim and the method, and cannot yet check either against the table.
David Sinclair: a second reprogramming program, and an NAD caveat
David Sinclair is a professor of genetics at Harvard Medical School, the author of Lifespan, and the chairman of the board of Life Biosciences. His week was mostly short posts pointing at published work, with one exception: a company result he described himself.
OSK in rats with liver disease, and a program called ER-300
On October 17 Sinclair posted a thread on reprogramming in rats with MASH, the fatty liver disease that progresses to inflammation and scarring 6. Rats treated with OSK — the three genes OCT4, SOX2, and KLF4 — survived at 100% in the MASH model, against 50% for OSKM; in MASH with cirrhosis the figures were about 90% and 45% 6.
Liver injury markers followed the same split. AST, ALT, and bilirubin were significantly lower with OSK in both chronic models, and OSKM showed no comparable protection 6. Fibrosis markers collagen I, alpha-smooth muscle actin, and desmin fell with OSK and the change held on histology, alongside lower myeloperoxidase and malondialdehyde; histological disease scores and portal pressure improved in both models 6.
The safety comparison is the striking part. OSKM-treated rats developed liver tumors, with elevated AFP and CEA tumor markers in the MASH model 6. Sinclair says ER-300 is being developed for liver disease, which makes it the company's second epigenetic-restoration program after ER-100 in glaucoma 6.
Read this as company preclinical work. The numbers come from Sinclair's own thread, no paper or company release for the liver program surfaced in the window, and the graphic attached to the thread is labelled as made with AI 6. The ER-100 readout covered here last week was a safety result in three patients; ER-300 has no human data.
An NMN bone result that used two drugs at once
Sinclair's October 18 post shares a mouse study on bone loss, and the detail that matters sits in the design 7. From 12 to 18 months of age, middle-aged mice received H-151, a drug that blocks STING, an immune-signaling pathway that turns inflammatory with age, together with nicotinamide mononucleotide, or NMN, a NAD precursor sold as a supplement 8. The combination preserved bone density and structure, increased new bone formation, lowered inflammatory markers, and improved NAD⁺ levels and mitochondrial function in the bone-marrow stem cells that build bone 8.
The mechanism explains why the two were paired. Aging marrow fat cells release a protein called DPP4 that reinforces inflammatory STING signaling, and STING raises the enzyme CD38, which degrades NAD and NMN outside cells 8. That cuts the NAD supply reaching bone-forming cells, so blocking STING and adding NMN attacked one deficit from two ends 8.
Two limits follow from that design. Lifespan News notes that giving the drugs together makes their separate effects hard to disentangle, and that the study was small 8. Alendronate, the standard osteoporosis drug used as a positive control, produced broadly similar improvements in bone structure 8.
A menopause paper, and a finasteride caveat in flies
Two shorter items from the same feed. On October 15 Sinclair flagged the Nature Medicine paper on the menopause transition, along with an interview with its senior author, Uri Alon 11. The paper reconstructs hormonal timing from more than 300 million lab results, and its central finding is covered under Rhonda Patrick below 12.
On October 18 he posted a study of finasteride, the hair-loss drug sold as Propecia, given to fruit flies 13. The treated flies showed more intestinal reactive oxygen species and shorter lifespans, with reduced starvation resistance in males, altered neuromuscular junction structure, and worse locomotor performance 13. His framing was "just FYI" 13. A fly study of a drug millions of men take carries a signal worth knowing about; how it translates to a man taking a tablet daily is untested 14.
Brown fat, in 101,243 scans
Sinclair's October 15 post describes brown fat under the arm and on the back as cold-activated tissue that generates heat, and reports an association with fewer cardiometabolic diseases and better glucose, lipid, and inflammatory markers 15. Sinclair's post describes a study of 8,700 patients; the Nature paper behind it screened 101,243 PET-CT records and quantified brown fat activity in 8,709 people with detectable tissue 16.
Detectable brown fat came with 58% lower odds of type 2 diabetes and 47% lower odds of chronic ischaemic heart disease, and with lower odds of depressive episodes and anxiety disorders 16. The axillary depot, under the arm, was the one most strongly tied to favorable cardiometabolic outcomes and a healthier distribution of white fat 16.
Two findings cut against a simple story. People with detectable brown fat also had higher total and LDL cholesterol and lower vertebral bone density, and the authors call the bone finding's significance uncertain 16. The study is retrospective, drawn from a cancer-center population, and the scans were taken without cold stimulation, so glucose uptake is an indirect measure of heat production 16.
Medication screening turned up losartan, a common blood-pressure drug, which raised brown-fat thermogenesis in cultured cells and energy expenditure in mice 16. Its effect on human brown fat sits untested.
Blueprint: a full training week, written in the first person
Blueprint, Bryan Johnson's protocol company, published once in the window: a training guide on October 14, under Johnson's own byline rather than a staff writer's 3. The post covers ground rules, his own routine, a seven-day sample, and pre- and post-workout nutrition.
The rules, and the week
It opens with a population number. Eleven minutes of daily exercise is linked to a 23% lower risk of early death, and the post links that claim to a paper in the British Journal of Sports Medicine 317. The four categories it asks a reader to cover each week are strength training, zone 2 cardio, high-intensity cardio, and mobility, flexibility, and balance 3.
The specific advice is conventional and concrete: two to three strength sessions a week built on compound movements, progressive overload, and four to six 30-second all-out efforts three times a week as the best return on time 3. Hard sessions should finish at least four hours before bed 3. Johnson's own targets are at least 150 minutes of zone 2 a week, at least 75 minutes of high-intensity work with about 10 minutes near maximal, and daily mobility 3.
The sample week runs from a 60-minute strength and moderate-cardio session on Monday to 20 to 30 minutes of yoga and 15 to 20 minutes of meditation on Sunday 3. Thursday is a Norwegian 4x4: four rounds of four minutes at 85% to 95% of maximum heart rate, separated by three minutes of easy work 3. Tuesday is eight rounds of 20 seconds all-out with 20 seconds of rest, which takes about five minutes 3.
Nutrition gets two timings: eat one to two hours before training, and eat protein and complex carbohydrates within an hour afterward 3. Johnson's pre-workout drink is his Longevity Mix with creatine, and the post links to the store for every product it names 3.
The page works as a training plan and a shop page at once. The 23% figure describes an association at one level of measured activity, which is a different object from a dose to aim at 17.
Rhonda Patrick: berberine's numbers, and a phase 3 miss
Rhonda Patrick is a biomedical scientist and the host of the FoundMyFitness podcast. Her newest episode is still the October 9 Q&A; this week's output was a Science Digest on October 16 and a run of posts 1819.
Berberine, with a dose and a sex difference
The October 18 post works through berberine, a plant compound sold as a supplement, and gives numbers a reader can hold 4. A meta-analysis pooling 14 placebo-controlled trials found LDL cholesterol about 18 milligrams per deciliter lower on average 4. Newer randomized evidence adds ApoB, the particle count that tracks atherosclerosis risk: in a placebo-controlled trial of 100 women, 500 milligrams twice daily for 12 weeks lowered ApoB by about 13 mg/dL relative to placebo 420.
The sex difference is the part she finds interesting. ApoB fell in both men and women, with a larger response in women, and that may be a dosing effect: at the same dose, women had almost three times the blood exposure to berberine 4. Early clinical evidence also suggests a reduction in artery plaque and a modest fall in TMAO, a gut-microbe metabolite implicated in atherosclerosis 4.
Her own word for the compound is "promising" 4. The lipid numbers rest on placebo-controlled trials; the plaque and microbiome findings come from earlier, smaller studies 4.
The NR trial her digest led with
The Science Digest's first item is a negative phase 3 trial, and it matters because it tested a supplement in people with a disease rather than in mice 19. Researchers in Norway randomized 410 people with Parkinson's diagnosed within the previous two years to nicotinamide riboside, 500 milligrams twice daily, or placebo for 52 weeks 5. Nicotinamide riboside is an NAD precursor sold as a supplement, and NAD, a molecule involved in cellular energy production, is what Sinclair's feed returned to repeatedly this week 719.
The result went the wrong way. The combined movement and non-movement symptom score rose 2.45 points on the supplement and fell 0.27 points on placebo, a 2.72-point difference favoring placebo 5. That gap sits below the 5.2 and 6.7 points the trial defined as clinically important worsening and improvement 5. Non-motor symptoms worsened more on the supplement, by 4.22 points on a separate 0–360 scale 5.
The mechanistic detail is the one to keep. Blood NAD rose markedly, brain imaging showed no clear rise in brain NAD against placebo, and dopamine transporter imaging showed no difference in the loss of dopamine nerve terminals 519. Patrick's reading is that the trial challenges the idea that nicotinamide riboside makes the brain more resilient to Parkinson's disease, with dose, duration, and disease stage left open 19.
Serious adverse events were less common on the supplement than on placebo, 8.3% against 14.1%; the signal was on efficacy 5.
The menopause cliff, measured 12 to 15 years early
The October 13 post covers a Nature Medicine paper that reconstructed the menopause transition from more than 300 million lab results 1221. The dataset covered about 36,000 women in US health surveys and 1.3 million in Israeli medical records, compared against men to separate menopause effects from ordinary aging 19.
Two numbers carry the finding. Fifty-two of 90 physiological measures shifted abruptly around menopause, against gradual change in men, and changes in anti-Müllerian hormone, follicle-stimulating hormone (FSH), and estradiol began accelerating an estimated 12 to 15 years before the final period 19. Current hormone therapy users showed smaller shifts in many measures, especially bone, liver, kidney function, and fluid balance 19.
Osteoporosis, heart attack, and stroke became more prevalent after menopause, anemia less so, and sleep difficulty and depressive symptoms rose temporarily around the transition 19. The design is retrospective, reconstructing trajectories from medical records, which makes the comparison between hormone therapy users and nonusers an association 19.
Cross-expert check
Exercise: two training weeks in the same seven days
Attia and Blueprint landed on training in the same week, and they diverge on one element that matters for anyone past 50. Blueprint's template is built on compound movements — goblet squats, kettlebell swings and farmer's walks, lunges, step-ups — with progressive overload as a rule 3. Attia describes moving away from heavy barbell squats and deadlifts and weighing benefit against injury risk more deliberately 1.
They agree on more than they differ. Both put consistency ahead of optimization, both keep a zone 2 base, and both include hard intervals; the argument is about how much cardio volume and which lifts 13. Blueprint's plan scales down for a beginner, with two or three intervals instead of four rounds and one strength session counting as a win 3. Attia's revision prices in the injury risk that comes with the heaviest versions of those lifts 1.
NAD: a mouse result and a human failure in the same week
The sharpest disagreement of the week concerns NAD precursors, and it is a disagreement about evidence tiers. Sinclair's feed carried mouse work on NMN and a separate result in which overexpressing SIRT1, an NAD-dependent enzyme, protected mice against weight gain, heart mitochondrial dysfunction, and glucose problems on a high-fat diet 722. Patrick's digest carried a 410-person phase 3 trial in which nicotinamide riboside raised blood NAD and failed to help, with brain NAD unchanged on imaging 519.
Both can be true at once. The mouse work asks whether a pathway can be moved; the trial asks whether a pill changes a disease. What the trial adds is the tissue question: blood NAD is easy to raise, and the brain did not follow 19.
Menopause: one paper, two audiences
Patrick and Sinclair flagged the same Nature Medicine paper within three days of each other 12. Her post leads with the timing, hormone changes starting 12 to 15 years before the last period, and with the body-wide shifts 21. His post points readers to an interview with the paper's senior author, Uri Alon 11. Both are reading the same reconstruction, and neither adds data the other has.
What to carry forward
- If you are cutting calories, keep protein at 1.4 grams per kilogram or above; Attia calls that the one number he is adamant about across low-carb, low-fat, and pescetarian diets 9.
- Judge an NAD supplement on tissue, not blood: in the Parkinson's trial, blood NAD rose sharply while brain imaging showed no clear change 19.
- Hold the NMN bone result at mouse scale; the experiment gave NMN with a STING inhibitor, could not separate the two, and alendronate matched the structural benefit 8.
- If you take finasteride, the fly study is a signal to watch, and the human question stays open 14.
- Timing matters around menopause: hormonal changes begin accelerating 12 to 15 years before the final period, and 52 of 90 measures shift abruptly at the transition 19.
- Blueprint's week is a usable template if you want a structure — 150 minutes of zone 2, 75 minutes hard, two or three strength sessions — and Attia's caveat is to drop the heaviest lifts you cannot recover from 13.
References
- 1#411 ‒ AMA #90: Strong convictions, loosely held
peterattiamd.com
- 2
- 3Bryan Johnson's Workout Protocol
blueprint.bryanjohnson.co
- 4
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- 10Metformin and cancer: active surveillance needed
peterattiamd.com
- 11
- 12
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- 18FoundMyFitness episode list
foundmyfitness.com
- 19FoundMyFitness Science Digest
foundmyfitness.com
- 20
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- 22
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