A couple of weeks before this episode, Dr. Su's pickleball coach asked him a simple question: "What's the best thing that you'd suggest I take for longevity?"
On this solo episode of the Functional Medicine Reality Podcast, TruWellness Medical Director Dr. Mark Su takes that question as a challenge. If he's forced to give one answer, what would it be? Here's what he landed on, in plain English.
Listen to the full episode
Episode 34 – Best Supplement for Longevity: Creatine, NAD, HRT, or Something Else Entirely
Why it's a hard question
Dr. Su admits he almost hates questions like this, because "there's no one size fits all."
Before answering, he'd want to understand a few things:
- Your definition: how do you define longevity, first and foremost?
- Your goals: what are you really after?
- Hidden goals: sub-goals you may not even be aware of yet, which often come out with enough conversation.
Still, he took the question as a challenge to himself. His answer is aimed at people in his and his friend's general age range, roughly 45 to 65. He also notes he has every right to change his opinion over time.
Dr. Su's four-part answer
He set out to name one thing and ended up with four. As he puts it:
I just gave a four-part answer, all right? I couldn't help myself.
Dr. Mark Su, MD · Medical Director
The answer depends on one big question: do you want to feel younger, or actually be younger?
If you want to feel younger
Creatine or HRT
- Off the cuff: creatine, the cheap and convenient option.
- More personalized: hormone replacement therapy, based on testing and whether you even warrant it.
If you want to be younger
NAD or bio age testing
- Off the cuff: NAD, for all comers, with no testing or other details.
- More precise: biological clock testing, rather than a one-size-fits-all approach.
Being younger and healthier isn't always something you'll feel. That's why he separates the two goals.
Biological age testing: find your weakest link
Dr. Su's test of choice is the TruDiagnostic TruAge test. He says the goal goes well beyond learning one number:
- Your biologic age: the starting point.
- Your rate of aging: perhaps more important.
- Your weakest link: especially important. Among the 10 to 12 body systems scored, which one or two deserve your attention so your body as a whole can be younger and healthier?
A kidney example
Say someone has a kidney condition they don't know about, and it looks normal on conventional testing like BUN, creatinine and maybe even urine microalbumin. Newer, more sensitive markers could show that the kidneys are their weakest link.
I cannot tell you that taking NAD is going to help you with your kidneys. I cannot tell you that taking creatine or HRT is going to help you with your kidneys.
Dr. Mark Su, MD · Medical Director
What the evidence really says
For fun, Dr. Su put the question to Claude, his AI program of choice: if a mid-50s male patient asks for a single best supplement or intervention for longevity, what are the top considerations?
The first point, he says, reflected his own thinking: nothing sold as a supplement has randomized controlled trial data with death or major illness as the endpoint. Instead, the evidence falls into a hierarchy:
- Robust epidemiologic cohort association: the strongest data. Examples: VO2 max, muscle mass and some HDL-related metrics.
- Surrogate marker trials: such as statins and apolipoprotein B, metformin and blood sugar markers, or omega-3 and triglycerides.
- Mechanistic and animal data: examples include rapamycin, senolytics ("zombie cell" supplements) and NAD.
- Practitioner consensus with weak or absent controlled data: including most peptides and many "longevity stacks."
Dr. Su is candid about where his own tools fall. He says he's a fan of peptides and uses them, but he's concerned that their monetization "has become a whole different animal." He also uses rapamycin and NAD, but he's cautious about how he presents them to people.
Why VO2 max comes out on top
The AI's bottom line: if the patient means any intervention, not just supplements, structured exercise targeting VO2 max improvement (a zone two base plus interval work) is the most defensible single answer. Dr. Su notes that many experts in the longevity world say the same thing.
The challenge is that it takes work:
It's a lot easier to take pills than to increase your VO2 max through exercise.
Dr. Mark Su, MD · Medical Director
How to approach it
- Get tested: you might meaningfully benefit from official, accurate VO2 max testing to see where you're at.
- Track it: use that as a metric, with less expensive gauges along the way, then retest from time to time.
- Train strategically: just walking or running more won't necessarily get you there. Talk to a practitioner or trainer who understands it.
Where IV ozone fits
As an in-between, Dr. Su says he's "a big fan of IV ozone." He describes a comparative trial among rugby players who all trained the same way. As he recalls it, those who also did one-pass IV ozone sessions improved their VO2 max by at least 18% to the low 20% range more than teammates who only did the training.
Honesty over hype
Dr. Su says this is the nature of functional medicine, for chronic illness and longevity alike: we don't have all the data we'd like. What matters is how decisions get made.
- Be thoughtful and methodical, and base decisions on as much rationale as possible.
- Admit what isn't known, and don't overstate it to colleagues or patients.
- Weigh the risks: time, money, effort, and especially side effects and potential harm.
- Decide together, with the patient's best interest at heart.
It just takes, all it takes is clear communications and transparency and integrity.
Dr. Mark Su, MD · Medical Director
Dr. Su's three summary points
- His best-supplement answer is the four-part answer above: creatine, HRT, NAD and biological age testing, depending on your goal.
- The best data-backed answer for improving longevity is increasing your VO2 max.
- Evidence comes in tiers. Practitioners need to be fair with patients and not oversell or overpromise.
From TruWellness
Longevity services at TruWellness in Newburyport
Several of the options in this episode are available at our Newburyport office:
- NAD+, as an injection or IV
- TruVitality hormone therapy: TRT for men and HRT for women
- Biological age testing, part of our AgeWell program
- VO2 max testing
- Ozone IV
What to expect
- A real conversation about your goals and what you've already tried.
- A plan built around you, using the services that fit your goals.
Patients come to our Newburyport office from Amesbury, Newbury, Salisbury, Haverhill and across the North Shore and the Merrimack Valley.
Book a ConsultationThis article is for education only and isn't medical advice. Talk with a licensed provider about what's right for you.