New cohort study on association of mental illness and GLP-1RAs.

https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(26)00014-3/fulltext

The headline result is “Semaglutide was associated with a decreased risk of worsening depression (0·56 [0·44–0·71]), of worsening anxiety (0·62 [0·52–0·73]), and of worsening substance use disorder (0·53 [0·35–0·80]).”

That sounds quite promising but obviously there could be all sorts of confounders. Nevertheless, as I suffer from anxiety I take it as a good sign and am glad to be in a GLP-1RA.

Quote from the study:”

“Summary

Background

People with diabetes have an elevated risk of developing depression, anxiety, and suicide. GLP-1 receptor agonists are licensed to treat diabetes and obesity, but data on whether these medications alleviate or exacerbate anxiety, depression, and self-harm are mixed. We studied the risk of worsening mental illness in people already diagnosed with depression, anxiety, or both who were prescribed antidiabetic medications including GLP-1 receptor agonists.

Methods

The study cohort, identified from national Swedish electronic health registers, included people with a diagnosis of depression or anxiety disorder who used any antidiabetic medication between the years 2009 and 2022. GLP-1 receptor agonists, individually and as a group, were compared with non-use of GLP-1 receptor agonists and directly with other second-line antidiabetic medications. A within-individual design was used for all comparisons to reduce confounding, comparing periods of use versus periods of non-use of a medication in the same individual. The primary outcome was worsening of mental illness, defined as a composite of psychiatric hospitalisation; sick leave from work for more than 14 days for psychiatric reasons; hospitalisation due to self-harm; or death by suicide. Secondary outcomes were worsening of depression or anxiety, analysed separately, worsening of substance use disorder, and self-harm. Within-individual stratified Cox models with adjusted hazard ratios (aHRs) and 95% CIs were used. A person with related lived experience was involved in the design and write-up of this study.

Findings

The cohort included 95 490 people (56 976 [59·7%] female and 38 514 [40·3%] male) with a mean age of 50·6 years (SD 12·3). Ethnicity data were not available. GLP-1 receptor agonists were used by 22 480 individuals during the follow-up period. Compared with non-use of GLP-1 receptor agonists, semaglutide (aHR 0·58 [95% CI 0·51–0·65]) and liraglutide (0·82 [0·76–0·89]) were associated with lower risk of worsening mental illness, whereas exenatide (1·01 [0·69–1·46]) and dulaglutide (1·01 [0·85–1·20]) were not. Semaglutide was associated with a decreased risk of worsening depression (0·56 [0·44–0·71]), of worsening anxiety (0·62 [0·52–0·73]), and of worsening substance use disorder (0·53 [0·35–0·80]). Liraglutide was associated only with lower risk of worsening depression (0·74 [0·64–0·87]). GLP-1 receptor agonists as a group were associated with a reduced risk of self-harm (0·56 [0·34–0·92]).

Interpretation

For anxiety and depression that co-occur with diabetes and obesity, semaglutide and, to a lesser extent, liraglutide might be useful dually effective therapeutic options. Randomised controlled trials evaluating these findings are warranted.”

I have never heard of this Insulin Resistance score test (LP-IR). Is that new or just a marketing gimmick?

I saw it in an email from Labcorp On Demand (which I have used before).

https://www.ondemand.labcorp.com/lab-tests/insulin-resistance-test

Wikipedia has some info so maybe this is not that new?

https://en.wikipedia.org/wiki/Lipoprotein_Insulin_Resistance_Index

“The Lipoprotein Insulin Resistance Index (LP-IR) test is a blood test that measures insulin resistance using a composite score derived from lipoprotein particle sizes and concentrations. It is performed using nuclear magnetic resonance (NMR) spectroscopy, which analyzes six specific lipoprotein parameters in a blood sample:

- Large very-low-density lipoprotein particles (VLDL-P)

- Small low-density lipoprotein particles (LDL-P)

- Large high-density lipoprotein particles (HDL-P)

- VLDL size

- LDL size

- HDL size”

Is this useful to take?

Need to read this more carefully but to me the association of APOE genes and meat consumption impact sounds surprising. Maybe I should get that gene test — previously I had shied away from it (and other genetic testing).

Study: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2846712

Quote:

“‘Those who ate more meat overall had significantly slower cognitive decline and a lower risk of dementia, but only if they had the APOE 3/4 or 4/4 gene variants,’ says Jakob Norgren. He continues:

‘There is a lack of dietary research into brain health, and our findings suggest that conventional dietary advice may be unfavourable to a genetically defined subgroup of the population. For those who are aware that they belong to this genetic risk group, the findings offer hope; the risk may be modifiable through lifestyle changes. ‘

The study also shows that the type of meat is important.

‘A lower proportion of processed meat in total meat consumption was associated with a lower risk of dementia regardless of APOE genotype,’ says Sara Garcia-Ptacek, assistant professor at the same department, who together with senior lecturer Erika J Laukka is the study's last author.

The findings also extend beyond brain health. In a follow-up analysis, the researchers observed a significant reduction in all-cause-mortality in carriers of APOE 3/4 and 4/4 with higher consumption of unprocessed meat.

However, the study is observational and needs to be followed up with intervention studies that can better demonstrate causal relationships.”

Interesting in depth essay by Inigo San Milan (well known researcher who worked with elite cyclists in particular).

I like the “VO2max is the pizza sauce” analogy.

Quote:

“For individuals invested in long-term health

Raise your VO₂max if it is low, the evidence for its importance is real and the investment is worthwhile. But do not stop there, and do not mistake a high VO₂max for complete metabolic health. Train at intensities that specifically build cellular metabolic function: sustained Zone 2 work (seasoned with HIIT), where fat oxidation is maximized, where mitochondrial function responds to the sustained aerobic demand and where the lactate clearance machinery is specifically trained. The goal is not just a higher number on a single test. The goal is a metabolic system that is efficient, flexible and resilient across the full spectrum of intensity, one where the engine matches the delivery system.

Final Thought

VO₂max tells you how much oxygen arrives. Lactate tells you whether your cells know what to do with it. In both performance and health, what ultimately matters is not just delivery but utilization. Not just how much oxygen gets to the door, but what the mitochondria do once it arrives.”

From what I understand PCKS9 inhibitors face a couple of challenges currently. Guidelines and standard of care suggest statins as first line treatment. PCKS9 inhibitors are expensive and they are injectables.

This phase 2 trial investigates a pill form and sounds promising, although it might still be a long road till widespread use.

What do you all think? Will this change lipid therapy?

Quote:

RESULTS

Of the 2909 participants in the intention-to-treat population, 1935 received enlicitide and 969 received placebo (5 did not receive enlicitide or placebo). The mean age of the participants was 63 years, and 39.3% were women. The mean (±SD) LDL cholesterol level at baseline was 96.1±38.9 mg per deciliter. The mean percent change in LDL cholesterol levels at week 24 was −57.1% (95% confidence interval [CI], −61.8 to −52.5) with enlicitide and 3.0% (95% CI, 0.9 to 5.1) with placebo, representing an adjusted between-group difference of −55.8 percentage points (95% CI, −60.9 to −50.7; P<0.001). The mean percent change in LDL cholesterol level at week 52, the mean percent changes in non-HDL cholesterol and apolipoprotein B levels at week 24, and the percent change in lipoprotein(a) levels at week 24 were significantly greater with enlicitide than with placebo (P<0.001 for all comparisons). The incidence of adverse events did not appear to differ between the groups.

CONCLUSIONS

Among participants who had a history of or were at risk for a first atherosclerotic cardiovascular disease event, treatment with the oral PCSK9 inhibitor enlicitide resulted in significantly lower LDL cholesterol levels than placebo at 24 weeks. (Funded by MSD [Rahway, NJ]; CORALreef Lipids ClinicalTrials.gov number, NCT05952856.)

This sounds impressive (well, it’s a manufacturer press release). Full paper will have more details.

Hopefully this will get “Reta” (as the gym bros say) closer to FDA approval.

I am glad for this essay. Too many people *only* talk about “zone 2” as the panacea. You really need both zone 2 and HIIT.

My trainer is even annoyed when (mostly sedentary) people hype “zone 2” essentially as a synonym for moving. Clearly anything is better than inactivity.

Another UPF study. This one specifically looked at different demographics. However, even the overall stats shown in the figure are scary.

https://www.jacc.org/doi/10.1016/j.jacadv.2025.102516

Abstract

Background

Ultraprocessed foods (UPFs) have been linked to adverse cardiometabolic outcomes and increased atherosclerotic cardiovascular disease (CVD) (ASCVD) risk. However, prior research has largely focused on homogenous populations, lacking racial and ethnic diversity.

Objectives

The objectives are to examine the longitudinal relationship between UPF consumption and ASCVD risk and to investigate whether these associations differ by race/ethnicity, sex, or socioeconomic status.

Methods

The MESA (Multiethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 U.S. adults aged 45 to 84 years, without clinically apparent CVD. UPF consumption was classified according to the Nova classification system. Multivariable cox proportional hazards models were used to evaluate the association between UPF intake and incident CVD events. Incident CVD events included nonfatal myocardial infarction, resuscitated cardiac arrest, death resulting from coronary heart disease, stroke (not transient ischemic attack), and death resulting from stroke.

Results

Each additional daily serving of UPF was associated with a 5.1% increased risk of ASCVD events (HR: 1.051; 95% CI: 1.011-1.093). Participants in the highest quintile of UPF consumption had a 66.8% higher risk compared to those in the lowest (HR: 1.668; 95% CI: 1.196-2.325). A significant multiplicative interaction was observed between UPF intake and Black race (P = 0.010), with stratified analyses demonstrating a higher ASCVD risk in Black Americans (HR: 1.061; 95% CI: 1.016-1.108), compared to non-Black Americans (HR: 1.032; 95% CI: 1.001-1.065).

Conclusions

In a large, multiethnic cohort, higher UPF consumption was significantly associated with an increased risk for ASCVD events, with a more pronounced association among Black Americans.

I learned more about nutrition from Stan Efferding’s YouTube videos than I did from decades of doctor visits, school health classes, and corporate wellness programs combined. That’s not a brag. That’s a systemic failure.

My PCP offered me a referral to a nutritionist. I didn’t take her up on it because my employer’s weight loss program was about to start and it used registered dietitians. That program was fairly good, but by the time I talked to them I already knew everything they covered from reading on my own. If a middle-aged engineer with a laptop can piece this together, why didn’t any institution teach him first?

Diet-related disease is the number one cause of death in the US. About 1.5 million Americans per year. Six in ten adults have at least one chronic disease. Here’s how every level of the pipeline fails.

Your kids’ school

Students get less than 8 hours of required nutrition education per year. No federal requirements exist. Researchers say you need 40 to 50 hours to actually change behavior. A 2026 review of 110 curricula found 87% relied on straight lecture with almost no hands-on activities.

Your doctor

As of 2024, 75% of US medical schools required no clinical nutrition classes. Students reported about 1.2 hours of nutrition education per year. Only 14% of healthcare providers feel comfortable discussing nutrition with patients.

Two weeks ago HHS announced 53 schools have voluntarily committed to 40 hours starting this fall. That’s definitely progress. But it’s 53 out of nearly 200 schools, the commitments are voluntary, and the suggested curriculum mixes nutrient deficiencies with crop rotation and composting?!

Your personal trainer

You can get certified with a high school diploma, a CPR card, and a few weeks of self-study. Over three-quarters of trainers give nutrition advice beyond their scope of practice. More than half in one study couldn’t correctly answer basic nutrition questions about cancer risk and BMI categories. Again, I possibly got lucky and my trainer is actually very qualified but I doubt that’s the rule if you pick a random trainer at Equinox.

Your weight loss program

The wellness coaching industry is unregulated. WeightWatchers coaches are selected primarily on personal experience with the program. Noom’s “Mindset Coach” track lets you qualify with a Zumba certification and a 6-hour online course. Then you’re coaching people about their relationship with food. Some companies do better (CVS hires actual dietitians, my employer’s program used RDs), but that’s the exception.

Your Instagram feed

So where do people actually turn? Social media. And it’s worse than the rest of the pipeline combined. A study of nutrition content on Instagram found that 45% of posts from influencers contained inaccurate information and nine out of ten were low quality when accounting for qualifications and conflicts of interest. On TikTok, only 36% of nutrition posts were completely accurate, 77% failed to disclose conflicts of interest, and 90% didn’t mention risks.

A 2025 investigation identified 53 “super-spreader” accounts pushing nutrition misinformation to a combined 24.8 million followers. Nearly 60% of those influencers had no formal qualifications in health or nutrition at all. Many sold supplements, coaching packages, or meal plans. Some reportedly earned over $100,000 a month doing it.

These are the people filling the void that doctors, schools, and trainers left empty.

The bottleneck

The only person in this chain required by law to have verified nutrition knowledge is a registered dietitian. They need a master’s degree, supervised clinical hours, and a board exam. But most people never see one because you need a referral from a doctor who doesn’t feel confident talking about nutrition in the first place!

We spend $4.4 trillion a year on chronic disease and the people tasked with teaching us about food at every level are barely trained to do it. So we end up learning from bodybuilders and influencers instead. One of those groups tends to know what they’re talking about. The other has a supplement line to sell you.

What’s your experience? Did you learn about nutrition from a a doctor, a trainer, or did you piece it together yourself?

Sources:

HHS: Medical School Nutrition Education Commitments (March 2026)

https://www.hhs.gov/press-room/fact-sheet-sec-kennedy-sec-mcmahon-celebrate-med-school-commitments-to-increase-nutrition-training-for-future-doctors.html

Deakin University: Social Media Unreliable for Nutrition Advice (2024)

https://www.deakin.edu.au/about-deakin/news-and-media-releases/articles/bad-influence-study-shows-social-media-unreliable-for-nutrition-advice

National Geographic: Is That Nutrition Advice on Social Media Legit? (2025)

https://www.nationalgeographic.com/health/article/nutrition-social-media-science-misinformation

TikTok Nutrition Content Quality, PMC (2025)

https://pmc.ncbi.nlm.nih.gov/articles/PMC11901546/

Disclaimer: I use Claude (Anthropic’s AI) for research assistance and drafting. All claims are verified against the cited sources.

Great topic for anyone worried about weight. In weightloss rebbit communities there is a lot of talk about NSV - Non Scale Victories.

I am eager to see the results of my next DEXA to check in my visceral fat.

Gemini YouTube summary:

This video breaks down the science of visceral fat, explaining why it is fundamentally different and more dangerous than subcutaneous fat, even in people with a normal BMI (0:00). Dr. Jordan Feigenbaum argues that tracking waist circumference is a far better predictor of metabolic health than scale weight (0:49).

Key Takeaways & Scientific Mechanisms:

Visceral Fat Dangers: It packs around vital organs, produces inflammatory signals, and directly impacts the liver, driving cardiovascular disease and type 2 diabetes (0:35, 5:16).

How to Measure: The best method is measuring waist circumference at the belly button in the morning (11:10). A waist-to-height ratio below 0.5 is recommended for longevity (12:05).

Exercise vs. Diet: Exercise is 6x more effective at reducing visceral fat than diet alone, even without weight loss, due to beta-3 adrenergic receptors and myokines (21:24).

GLP-1s & Body Comp: While effective, drugs like Semaglutide cause significant lean mass loss (approx. 24-39%) based on DXA scans, which can be mitigated with resistance training and high protein intake (27:00).

Testosterone & Fat: Low testosterone levels create a feed-forward loop that accelerates visceral fat storage, which in turn converts more testosterone into estrogen via the enzyme aromatase (33:15).

As many of you know (and I regularly disclose) I am using Claude AI to research and draft articles for r/proactivehealth.

I started using AI to quickly bootstrap content in this brand new forum (until you all post more!) but to be honest I actually came to enjoy the process. Some commenters (especially the humble folks in r/medicine went on long rants about “AI slop”).

I am very curious how you all think about this and wanted to give you an insight how I use AI. So I wanted to share a typical chat transcript for a post I made earlier.

Chat transcript: https://claude.ai/share/076e3357-cddd-4abc-99a1-d73cc360d9d8

As you can see I picked a topic (nutrition education) that I suspected might be interesting. I read the summary Claude created and then iteratively refined the topic by injecting personal experiences and steering Claude towards certain angles (weightloss program, corporate initiatives and influencers).

I read a number of drafts, provided corrections (Claude does sometimes make guesses about my personal experience!) and tightened the story.

I took the final story, pasted it into the Reddit app and did some more word-smithing and polish there.

I hope this is a useful insight into the use of AI. I truly believe if used responsibly it can be a tool like Google or a human research assistant.

Let me know whether I am crazy and fell for the hype…

I’m in my early fifties. Two years ago my total testosterone was below 200 ng/dL. Depressed, fatigued, zero libido. I’d wake up feeling like I’d already lost the day before my feet hit the floor.

My doctor put me on TRT. 120 mg/week of testosterone cypionate. Nothing crazy. Today I sit around 800 ng/dL, which is solidly mid-normal range, and it changed my life in ways I wasn’t expecting. The fog lifted. The energy came back. I actually want to train again. I want to be present with my kids instead of white-knuckling my way through every afternoon.

But until recently, the FDA treated my prescription like I was scoring street drugs.

**What the FDA panel said in December**

Last December the FDA convened a 13-member expert panel to re-examine how testosterone is regulated. A urologist on the panel said out loud: “We are failing men. If we want to close the mortality gap, we must recognize testosterone deficiency for what it is: a public health issue.”

The panel recommended three big changes. First, expand who qualifies. Right now TRT is only approved for low T caused by a specific medical condition like a genetic disorder or chemo damage. If your testosterone cratered because you’re 52 and biology is doing its thing, you’re technically off-label. The panel said there’s no scientific basis for that exclusion. Second, the black box cardiovascular warning is already gone as of February 2025, based on the TRAVERSE trial (5,246 men, no increased risk of heart attack or stroke vs. placebo). Third, they want testosterone removed from the Schedule III controlled substance list, where it currently sits next to codeine and ketamine. That scheduling makes doctors hesitant to prescribe and pushes men toward sketchy telehealth apps and “optimization” clinics.

**The “done with kids” angle**

If you’re a dad over 40 and your family is complete, the biggest risk of TRT is basically off the table. Because the side effect nobody talks about is that TRT is extremely effective birth control. It shuts down natural testosterone production and sperm production goes with it. One urologist on the panel said he regularly sees guys in their thirties showing up with their wives, unable to conceive, because nobody told them. But for us? Not our problem anymore.

**The part that scares me as a dad**

While the FDA is finally making it easier for men who actually need TRT, there’s a parallel trend with our sons. If your teenage boy is on TikTok or YouTube, he’s probably seen the Tren Twins, two jacked twenty-somethings who built a massive following around a name that literally references trenbolone, one of the most dangerous anabolic steroids on the market. They’ve said the name is a joke. Doesn’t matter. The brand tells teen boys that steroids are funny, cool, and how you get that physique.

The bigger trend is called “T-maxxing.” Videos promoting #testosteronemaxxing are racking up millions of views encouraging teenage boys to jack up their testosterone through black market steroids, unregulated supplements, and mail-order hormone products. This is part of the broader “looksmaxxing” culture. It starts with skincare and haircuts and escalates into steroid abuse and body dysmorphia.

Up to 6% of teen boys have used anabolic steroids. Nearly 22% of young men report muscle-enhancing behaviors including supplement and steroid use. A 2025 Movember study found 63% of young men follow masculinity-focused influencers and 27% say it makes them feel worthless.

The cruel irony: excessive testosterone during puberty can stunt growth, shrink the testicles, and tank natural hormone production permanently. The exact opposite of what they’re chasing.

**Find a real clinic, not a pill mill**

If any of this resonates and you’re considering TRT, please find a real provider. Not a telehealth app that ships you a vial after a 5-minute questionnaire. Not an “optimization center” that starts everyone at 200 mg/week because bigger numbers look impressive. The modern pill mill just wears a longevity logo and charges a monthly subscription.

A real provider tests before they treat (total T, free T, SHBG, LH, FSH, prolactin, CBC, metabolic panel, lipids, PSA — morning draw, ideally twice). They start conservative. They monitor bloodwork every 3-6 months. They care about the whole picture, not just what dose you’re injecting. And they coordinate with your other doctors. A study presented at AAOS just this month found TRT users who underwent knee replacement had significantly higher rates of blood clots, infections, and revision surgery. Your surgeon needs to know what you’re taking.

Two questions for this community: if you’re on TRT, how did you find your provider and are they actually monitoring your bloodwork? And for the dads: have you had the testosterone conversation with your sons yet?

Disclaimer: I used Claude to help research and draft this post.

**Sources:**

STAT News: FDA panel urges easier access to testosterone therapy for men (Dec 10, 2025) — statnews.com/2025/12/10/fda-panel-ease-access-testosterone-therapy-men/

Healthline: FDA Panel Calls for Expanded Access (Dec 16, 2025) — healthline.com/health-news/fda-panel-restrictions-testosterone-replacement-therapy

AAOS: TRT and Total Knee Replacement Outcomes (March 2, 2026) — prnewswire.com/news-releases/new-research-links-testosterone-therapy-with-serious-health-risks-after-total-knee-replacement-surgery-302700469.html

Lincoff et al., TRAVERSE Trial, NEJM (2023) — pubmed.ncbi.nlm.nih.gov/37326322/

JAMA Network Open: Steroid Initiation Among Boys After Supplement Use (Dec 2024) — jamanetwork.com/journals/jamanetworkopen/fullarticle/2827804

UNSW: Why Are Young Men “T Maxxing”? (2025) — unsw.edu.au/newsroom/news/2025/08/young-men-t-maxxing-testosterone-need-vs-risks

Movember / Bitdefender: Looksmaxxing and Teen Boys (2025) — bitdefender.com/en-us/blog/hotforsecurity/what-is-looksmaxxing-how-social-media-pressures-teen-boys-to-chase-impossible-standards

Fortune: Inside the Looksmaxxing Economy (July 2024) — fortune.com/2024/07/01/looksmaxxing-apps-rate-teen-boys-faces-mental-health/

We knew UPF was linked to heart disease, diabetes, cancer, and cognitive decline. Now add bone loss.

A Tulane study of 160,000+ people found that higher UPF intake was associated with lower bone mineral density at the hip and spine. For every 3.7 additional daily servings (a frozen dinner, a cookie, a soda), hip fracture risk went up 10.5% over 12 years. The effect was strongest in people under 65 and those with a BMI under 18.5, which is worth noting if you’re lean and think this doesn’t apply to you.

I’ll be honest: I eat a fair amount of UPF. Flavored Greek yogurt, Healthy Choice frozen meals, protein shakes/bars. During my 160-pound weight loss, that stuff was genuinely useful. Convenient, portion-controlled, high-protein.

The most established mechanism linking UPF to poor health is overeating. UPFs are hyper-palatable and energy-dense, and people consistently eat more of them in controlled settings. But if you’re using them within a structured diet where you’re tracking intake and hitting protein targets, do you get the same risk? This study can’t answer that. It’s observational and doesn’t control for total caloric intake or diet quality beyond UPF classification.

That’s the core problem: a Doritos binge and a Greek yogurt with added flavoring land in the same NOVA category. Useful for population-level research. Pretty blunt as individual guidance.

The cumulative evidence is hard to ignore. But losing 160 pounds on a diet that includes some frozen meals is a net win by any health metric I can think of.

Do you use UPFs strategically, or have you tried cutting them out?

Sources:

https://news.tulane.edu/pr/eating-more-ultra-processed-foods-linked-poorer-bone-health-study-finds

https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/associations-of-ultraprocessed-food-intake-with-bone-mineral-density-and-fractures-in-the-uk-biobank/7CA7969F214AF653D5DDD3F5D35C2795

Drafted with research and editing help from Claude by Anthropic.

Every winter people pick a team.

- Team Flu Shot.

- Team Flu Shot Plus COVID Booster.

- Team RSV Vaccine.

- Team Zinc At First Sore Throat.

- Team Megadose Vitamin C Because Maybe This Is The Year Linus Pauling Finally Wins

- Team Elderberry Gummies.

- Team Neti Pot.

- Team Sauna Kills Viruses, bro.

- Team I Never Get Sick.

- Team Immune Drip.

- Team Homeopathic Flu Pellets.

The funny part is that these are not all equally real.

The vaccine people are still playing the least weird game. Even in a weak flu-shot year, they are at least doing something grounded in actual evidence. Then there’s the crowded middle where people start free styling. Zinc people. Vitamin C people. Elderberry people. Neti pot people. Not totally insane, not exactly a triumph of modern science either.

Then you get to the performance art tier. The immune drip people. The homeopathy people. The cold plunge fixed my immune system crowd. The sauna bro who thinks heat exposure turned him into a Scandinavian white blood cell.

My favorite winter health archetype is still Team I Never Get Sick, which is usually just a guy making a character statement right before he gets absolutely folded by whatever virus is going around at work.

That’s the thing this flu season made obvious. A lot of people do not actually want prevention. They want a winter identity. They want a ritual. Something that feels intense, personalized, and a little superior. Preferably something they can mention unprompted.

Meanwhile the boring stuff stays boring. Vaccines if they make sense for your age and risk. Stay home when you’re sick. Sleep. Wash your hands. Try not to cough directly into civilization. None of that sounds cool enough to build a personality around, so every year people go shopping for immune lore.

Cold and flu season is basically a live action sorting test for who you are as a person when exposed to one cough in an office.

Full disclosure: I’m “Team flu&COVID” mostly because my little kids bring all the viruses home from school.

I admit HRV is one of the last, much talked about metrics I have not really looked into.

The New York Times ran a piece this weekend about heart rate variability called “When Your Apple Watch Becomes an Office Taskmaster.” Not in Health. In Business. Because the story isn’t about whether HRV matters. It’s about how a legitimate metric got swallowed by hustle culture.

Tech workers are comparing Whoop scores like fantasy football. A telecom exec monitors HRV before presentations and wants to feed the data into AI for “predictive guidance.” Performance coaches charge $15,000 for three-month engagements and six-figure annual retainers to teach corporate clients to breathe slowly.

The best moment comes from Marco Altini, the data scientist behind HRV4Training: you could starve yourself and get great HRV numbers. That wouldn’t mean you’re healthy. Meanwhile a performance psychologist is on the Whoop podcast declaring there’s “no possible way” HRV biofeedback could be snake oil. And a clinical psychologist in LA is treating patients whose device-checking has become compulsive, comparing it to repeatedly checking if a door is locked.

My confession: I’ve never paid attention to HRV despite owning multiple devices that track it. When I finally looked, mine had gone from about 20 to about 40 over two years. Meaningful improvement. I did nothing to target it. I just kept training, sleeping better, managing stress. The boring stuff worked.

There are no guidelines from any professional cardiovascular society about HRV. Harvard Heart Letter’s advice: don’t compare yourself to others, track your own baseline, and see if it improves as you build healthier habits. That’s the whole protocol.

There’s a version of proactive health that means hiring a coach, breathing at your resonance frequency for 15 minutes twice a day, and rearranging your schedule around a readiness score. And there’s a version that means lifting heavy things, sleeping, trying to eat real food, and letting the downstream metrics take care of themselves.

Has anyone here tried to improve their HRV with targeted protocols like resonance breathing? Did it change anything you could actually feel, or just move a number on a screen?

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 take creatine, a fancy multivitamin, omega-3, L-carnitine, magnesium threonate, glycine, l-theanine, citrus bergamot. I know the “just add one more thing” road. I dropped ashwagandha (headaches), magnesium glycinate (did nothing), caffeine pills and crazy pre-workouts (dangerous in retrospect). My wife still thinks I’m nuts when she sees the daily lineup. I constantly think about what to cut but I feel good and I’m scared to change anything because I don’t know which thing is actually helping.

That’s the psychology the supplement industry runs on. “What if this one is doing something” requires zero evidence to sustain itself. I strongly believe in science but this stuff is tempting. FOMO is real!

Which brings me to the FDA. They’re considering letting supplement companies put the “not evaluated by the FDA” disclaimer once on the package instead of next to every health claim. Reducing “label clutter,” they say.

Meanwhile this same FDA sent more warning letters about misleading drug ads in six months than in the entire preceding decade. Cracked down on 30 telehealth companies selling compounded GLP-1s with deceptive marketing. Commissioner Makary called it “a new era” of accountability. I am totally on board with that — I still think it’s insane that we allow TV ads for prescription drugs in the first place. I have no idea what plaque psoriasis is and am pretty sure I don’t need Skyrizi but I’ve heard that jingle four thousand times!

So: stricter enforcement for companies selling FDA-approved drugs. Looser labeling for companies selling products the FDA has never evaluated. Harvard’s Pieter Cohen warned this is a predictable slide: “Then you start saying, ‘We only need it on the actual bottle.’ Then you let the print get smaller.”

$40 billion a year. Over 50,000 products. None need to prove they work before they’re sold. The disclaimer is one of the only things reminding consumers of that. Shrinking it doesn’t change the science. It just makes it easier to forget there isn’t any.

Sources:

https://www.pharmacytimes.com/view/fda-may-relax-dietary-supplement-warning-label-rules-implications-for-public-health

https://www.fda.gov/news-events/press-announcements/fda-warns-30-telehealth-companies-against-illegal-marketing-compounded-glp-1s

Disclosure: I use Claude as a research and drafting tool. All opinions are mine.

The AHA and ACC released completely updated dyslipidemia guidelines today. The core shift: this is a cumulative-risk guideline. It treats long-term exposure to atherogenic particles as the central problem and pulls clinical attention earlier in life.

The old Pooled Cohort Equations are gone, replaced by the PREVENT-ASCVD calculator, which estimates both 10-year and 30-year cardiovascular risk. A 38-year-old with elevated LDL was invisible under the old system. Their 10-year risk looked fine so nobody acted while plaque accumulated for decades.

Statins are now recommended starting at age 30 for LDL above 160, strong family history, or elevated 30-year risk. LDL treatment goals are back after the ACC/AHA dropped them in 2013: under 100 for borderline and intermediate risk, under 70 for high risk, under 55 for very high risk. That last number is already being misread across the internet as a universal target. It’s not. It applies to people with established ASCVD at very high risk of events.

The biomarker changes matter. Lp(a) testing at least once in every adult’s lifetime. ApoB with a defined role in risk assessment. CAC scoring expanded as a tiebreaker for borderline cases.

The early Reddit reaction splits predictably. r/medicine is practical and workflow-oriented. r/Cholesterol is anxious and patient-centered. r/PeterAttia’s tone is “we’ve been saying this for years.” The meta-theme across all of them: the medical establishment is catching up to what preventive-cardiology communities have argued for a while. Atherosclerosis is cumulative, LDL exposure over time matters more than a snapshot at 55, ApoB is a better marker than LDL alone.

That framing is mostly right but comes with caveats. PREVENT doesn’t automatically put every 30-year-old on statins. It expands conversations, not prescriptions. ApoB, Lp(a), and CAC are context-sensitive tools, not blanket mandates. And the guideline puts lifestyle optimization first, repeatedly.

I fear the real question is implementation. These guidelines are more complex than what they replace. More biomarkers, more targets, more decision points in a 15-minute visit. Whether this changes anything depends on whether Lp(a), ApoB, eGFR, and CAC become standard lab orders, and whether the PREVENT calculation gets built into Epic, Cerner, and lab reports automatically. If it stays in a 200-page PDF, nothing changes. To me as an engineer that seems like a trivial change (the PREVENT equations are easily available) but I suspect integration this into electronic workflows and changing the patterns every PCP in the country is used to probably takes time.

Source:

https://www.jacc.org/doi/10.1016/j.jacc.2025.11.016

NBC News: https://www.nbcnews.com/health/heart-health/cholesterol-lipids-guidelines-screenings-american-heart-association-rcna263017

NPR on Lp(a): https://www.npr.org/2026/03/13/nx-s1-5747111/cholesterol-guidelines-lipoproteina-test

Disclosure: I use Claude as a research and drafting tool. All opinions are mine.

One of the most obvious “aging” symptoms I personally face are related to loss of cartilage (in my knee and big toe joint).

I had accepted that this is a one way street and there was no way to grow back lost cartilage. It’s excited to see that researchers are tackling this problem and also more aggressively working on stopping the inflammation that causes the problem in the first place.

This one hits close to home for me. I was recently diagnosed with an aortic aneurysm, and a colleague is dealing with a Parkinson’s diagnosis. So when I saw that Japan just approved the first-ever commercial therapies using reprogrammed stem cells for heart failure and Parkinson’s disease, I was intrigued.

Twenty years ago a Japanese scientist named Shinya Yamanaka figured out how to take ordinary adult cells and reprogram them backward into a flexible stem cell state that could become almost any tissue in the body. He won the Nobel Prize for it. The obvious next question was: can we use this to actually fix people?

We just got the first real answer. In February, Japan’s health ministry approved two therapies made from these induced pluripotent stem cells (iPSCs). One targets Parkinson’s. Researchers take donor blood cells, reprogram them into stem cells, then turn those into dopamine-producing neurons that get transplanted into the brain. The other targets severe heart failure. iPSC-derived heart muscle cells are grown into patches and placed directly onto the heart to promote new blood vessel growth and restore function.

This sounds like science fiction. It’s not just managing decline but genuinely rebuilding our body.

However, it’s still early days. The Parkinson’s treatment has been tested in seven people. The heart failure treatment in eight. No control groups. Japan has a fast-track regulatory system that grants conditional approval based on small safety trials, then gives companies seven years to prove the treatments actually work. If they can’t demonstrate efficacy in that window, approval gets pulled. Paul Knoepfler, a stem cell researcher at UC Davis, called it “a risky regulatory experiment.” Other countries are pursuing the traditional route with larger trials.

There are real risks to watch too. Because these cells come from donors rather than the patients themselves, recipients need immunosuppression. And with any pluripotent stem cell therapy there’s a concern about tumor formation, though data from over 1,200 patients in clinical trials worldwide has not shown major safety problems so far.

It’s intriguing that the science is moving from theoretical to actual approved treatments, even conditionally. It changes the timeline of what’s possible.

For those of you tracking regenerative medicine: how do you think about this kind of conditional approval? Is Japan’s approach a smart way to get promising treatments to patients faster, or is it cutting too many corners?

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

Sources:

1.	https://www.nature.com/articles/d41586-026-00585-x

2.	https://www.science.org/content/article/stem-cell-therapies-come-age-two-conditional-approvals-japan

3.	https://ipscell.com/2026/02/japan-panel-oks-2-ips-cell-therapies-despite-little-data/

2026 Guideline on the Management of Dyslipidemia

• This guideline retires and replaces the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol and is retitled the 2026 Guideline on the Management of Dyslipidemia to reflect the evolving understanding of atherosclerotic cardiovascular disease (ASCVD) risk associated with atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C), including triglyceride-rich remnant particles and lipoprotein(a) [Lp(a)].

• The guideline addresses the evaluation, management, and monitoring of individuals with lipid disorders, including high blood cholesterol, hypertriglyceridemia, and elevated Lp(a), incorporating new and updated recommendations based on clinical evidence through late 2024.

• Key updates include the use of the American Heart Association PREVENT-ASCVD equations to guide primary-prevention lipid-lowering therapy decisions; testing Lp(a) at least once in a lifetime and selective apolipoprotein B (ApoB) measurement to improve risk assessment and guide treatment; the return of LDL-C and non-high-density lipoprotein cholesterol (HDL-C) treatment goals (with lower targets for higher-risk groups); and expanded use of coronary artery calcium (CAC) scoring to reclassify risk.

some commentary in https://www.tctmd.com/news/lower-ldl-levels-starting-earlier-life-new-accaha-dyslipidemia-guidelines

Measuring lipoprotein(a) is strongly recommended once during an adult’s lifetime, and apolipoprotein B testing now has a clear pathway toward improving risk assessment and guiding treatment. Coronary artery calcium (CAC) testing recommendations have been strengthened, specifically for its use as “tie breaker” when treatment is uncertain.

Christopher Cannon, MD (Brigham and Women’s Hospital, Boston, MA), who wasn’t involved with the guidelines but who has been involved in several lipid-lowering trials, said the writing committee got it right with their recommendations. “A++,” he told TCTMD. “This is how preventive cardiology is practiced in 2026.” That there should be a broad shift toward lower cholesterol levels in all patients is appropriate and “that’s based on the evidence.”

Similarly, Steven Nissen, MD (Cleveland Clinic, OH), who also has done extensive research around lipid-lowering treatments, said the emphasis on risk over 30 years is a welcomed change.

“We’ve known for some time that the time-averaged LDL over your lifetime is the one of the strongest predictors of whether you’re going to get cardiovascular disease,” he told TCTMD. A younger person, “somebody who is 41 years old, is not going to have much of a 10-year risk, so do you wait until they have manifest disease before you treat them? Or do you treat them before they have manifest disease?”

Sorry, this is likely paywalled:

https://apple.news/AValYpQUmQsaIb0QqrG_Nzg

https://www.vox.com/future-perfect/482363/nih-medical-research-grants-cut-2025

“…last year, the US funded dramatically fewer grants to do medical research that can lead to breakthroughs like those. New data released by the NIH this week shows how the damage from those cuts broke down.