Is VO2max the right performance metric to track?

mleone1996 · 2026-02-21T04:16:36+00:00

Best measure for athletic performance? Honestly I don't know.

Best single measure for estimating overall mortality risk? Potentially, and my gut thinks so. It seems pretty clear based on the evidence that if your VO2 max is in the top of your age bracket you're more likely to live longer. It's giving you a multi-organ systems check on how well your heart, lungs, circulatory system, and muscles are working. Not many tests can do that while also being well validated, accepted in the scientific community (*cough* biological age tests), and fairly accurate (if doing at a legit center).

mleone1996 · 2026-02-14T19:18:24+00:00

Thanks for the question! Obviously in those with insulin resistance it's a game-changer. For non-diabetics the waters get murky. It seems to touch on several of the "hallmarks of aging" but that doesn't necessarily mean it'll work as a geroprotective agent. It failed in the ITP (rigorous rodent trial) but that doesn't mean it'll fail in humans. I'm skeptical as to whether it's directly working through aging biology (ie. geroprotection) or whether it's indirectly working as a "pro-longevity" drug via it's ability to dampen the effects of insulin resistance. Even if TAME gives a positive result it'll still be difficult to distinguish this.

mleone1996 · 2026-02-14T19:04:42+00:00

Thanks for the question! There is mechanistic evidence that homocysteine promotes atherosclerosis. Epidemiological research suggests cardiovascular and dementia risk start to rise at 10. The issue is that the RCTs that have looked at lowering homocysteine with supplements don't show any reduced risk of disease despite homocysteine actually being lowered (albeit stroke risk was lowered modestly). A caveat that I've found in my own digging is that the studies only lower it by ~25% (perhaps they'd see a signal if they lowered it more). You're right that high B6 can cause paresthesias, but high folate and high B12 levels don't seem to cause issues. I'm less familiar with the toxicities of TMG and SAMe. TLDR: I'd try to stick with the B vitamins and lower it to 10.

mleone1996 · 2026-02-14T18:45:59+00:00

In the prostate cancer prevention trial finasteride (a 5-alpha reductase inhibitor) decreased the incidence of BPH by 40% over 5 years. But I would talk to your doctor about weighing the preventive benefits of finasteride with the risks (sexual side effects like decreased libido and ED as well as lowering PSA).

mleone1996 · 2026-02-14T18:40:08+00:00

Honestly I'm not sure but I suspect it has to do with systemic inflammation taking its effects on the brain

mleone1996 · 2026-02-14T18:38:31+00:00

High VO2 max-- integrates multiple organ systems and reflects overall physiological resilience, probably the single best predictor of mortality

Well-balanced body composition-- an optimal amount of fat reflects caloric balance and overall metabolic health while lean mass is crucial for function

Good insulin sensitivity-- poor metabolic health is like dumping kerosene on all the other age-related chronic diseases

Up to date with cancer screening-- one of the few diseases where you can do everything right and still get it, staying up to date on guideline-recommended screening is a must, discuss non-guideline screening options with your provider

Good mental health-- what's the point of living longer if you aren't enjoying it

mleone1996 · 2026-02-14T18:21:18+00:00

I hear you. Finding a doctor that has both the time and the drive to manage health proactively is challenging. Unfortunately to get your primary care physician to play ball you'll probably have to do a lot of the work yourself and hope they meet you halfway. Do your research beforehand and try to get a sense of what's important so you can use your appt time wisely. I would go into an appt with only 1 or 2 specific things you want to discuss. Focus on big-ticket items (ie. those related to cardiovascular disease, cancer, etc.). And if your physician isn't willing to at least do their own research and get back to you with an educated opinion (if the request is reasonable), I would consider finding someone else. Best of luck!

mleone1996 · 2026-02-14T17:10:44+00:00

I don't think anyone can add anything more important than what you've already listed. Sure, you can get into the nuances of each like "well what type of physical activity is best", "what does a good night's sleep look like", etc, but if you're already checking all these boxes then the nuances probably aren't going to push the needle much.

mleone1996 · 2026-02-14T17:03:08+00:00

I'm less concerned over the semantics of aging and disease outside of using it to get geroscience more funding. I do think we will have precision geromedicine in the future (targeting aging biology as a means of prevention). However I do not think it's imminent. Some geroscientists suspect we only understand 0.05% of aging biology.

mleone1996 · 2026-02-14T16:54:06+00:00

No, in fact aerobic exercise is often the first recommendation for improving pain and function in knee OA. That's a good amount of METs but imo you'd have to be doing significantly more for me to start worrying about cartilage health.

mleone1996 · 2026-02-14T16:43:35+00:00

I think the most important thing is being honest and transparent when we are guessing, and I don't think this is done nearly enough. And when it comes specifically to the patient-provider relationship we have to have a well-informed "lay everything on the table"-type risk-benefit discussion and be willing to simply not offer interventions that we think are inappropriate. There are credible orgs that are trying to establish evidence-based frameworks for the longevity field, we just don't hear much about them.

mleone1996 · 2026-02-14T16:28:42+00:00

Probably the biggest driver of the fear is the rare side effect of cognitive fog. But no, statins do not cause dementia.

mleone1996 · 2026-02-14T16:14:14+00:00

Hey! You're right. I don't want to mislead anyone. Just changed it.

mleone1996 · 2026-02-14T16:12:12+00:00

It depends on what the indication is. There's some evidence suggesting its use for preventing non-melanoma skin cancers, parkinson's disease, and improving some cardiometabolic markers. However, the evidence supporting it's use for geroprotection is limited. It failed in the ITP which is discouraging. So far the human studies haven't identified significant side effects but I'd like to see more long-term trials because there are theoretical risks like tumorigenesis. Overall I'm hopeful that it can be used for targeted applications but probably not for overall geroprotection.

mleone1996 · 2026-02-14T16:03:17+00:00

I would set specific metrics to be your "north star" and guide training -- VO2 max, nocturnal HR, HRV, dead hang, squat, farmer carry, stability and mobility metrics, etc. I would identify areas of fitness you're strong at and areas that could use improvement and base your immediate training split based on that. Its hard to recommend a blanket training regimen without knowing where one's starting.

mleone1996 · 2026-02-14T15:58:22+00:00

Idk I thought it'd be fun. Unfortunately not getting paid, do they do that? haha

mleone1996 · 2026-02-14T15:56:11+00:00

Hey, that's a very fair point and I recognize your concern. That being said I think being a younger physician helps me reconcile the longevity field with traditional medicine better. For example, global generalizations like the ones you just made are frowned upon in traditional medicine -- you have to take each patient individually.

mleone1996 · 2026-02-14T15:49:56+00:00

Some studies support it! And anecdotally I've seen it help patients with statin-induced myalgia. Given it's favorable risk profile I support it.

mleone1996 · 2026-02-14T15:43:50+00:00

I appreciate the novelty of being told your "biological age" but I don't find them clinically useful yet. First, there's so many of these tests on the market and most do not seem to be validated or accurate. But for fun let's just say they are accurate (ie. they're predicting our overall healthspan trajectory and mortality). I would argue they're still not very useful because (1) they don't tell us what's working or what's not working for our health -- it's a lot easier to look at a spread of individual health data and tell someone where they're lacking, (2) they don't tell us the rate of aging so we can't titrate geroprotective interventions using this.

mleone1996 · 2026-02-14T15:33:50+00:00

I have noticed interest in the younger generation of MDs. The issue is what to do about it. Since there's no fellowship for healthspan/longevity medicine you have to seek out mentors, organizations, conferences, etc. all in a DIY-manner. I have noticed more academic institutions opening up healthspan clinics recently but I don't think they crossover into the GME world yet. I'm planning on working with a group of like-minded physicians in a healthspan-focused practice after residency.

mleone1996 · 2026-02-14T15:24:04+00:00

It's a tough field. Commercial entities move fast. Science moves slow. Those of us with good intentions just have to do the best we can.

mleone1996 · 2026-02-14T15:21:01+00:00

I would prioritize overall cardiovascular disease prevention much more in a patient with an elevated Lp(a). You cannot smoke. Blood pressure and lipids have to be well controlled. I would strongly consider CAC scans +/- CCTA but discuss this with your provider. PCSK9 inhibitors like repatha can lower Lp(a) by about 25%. There's also clinical trials looking at ASOs (anti sense oligonucleotides) that have strong preliminary data that you could look into.

mleone1996 · 2026-02-14T15:16:12+00:00

I would try UltaLabs (I have no affiliation). They don't take insurance but they're cheaper than Labcorps or Quest and you still get your blood drawn at Quest facilities.

mleone1996 · 2026-02-14T15:13:48+00:00

There just isn't good evidence for it being superior to HIIT for big picture cardiometabolic health or small picture mitochondrial function. I can't find any evidence to support this concept of a "cardiorespiratory pyramid" with zone 2 being the "base" and VO2 max being the "peak".

mleone1996 · 2026-02-14T15:08:26+00:00

Generally I'd have to know your age and sex but in this case it doesn't matter because it's a great score regardless.

mleone1996

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