I've spent the last three years and roughly $4,200 testing longevity supplements on myself. I've run baseline blood panels, biological age tests (TruDiagnostic and TruAge), grip strength benchmarks, VO2max retests, and an embarrassing number of sleep trackers. I've also read more papers on senolytics, sirtuins, and NAD+ metabolism than is probably healthy for a layperson.
Here's the short version: most of what gets marketed as "longevity science" is sold on the back of mouse studies. A few supplements have genuinely solid human evidence. The rest live somewhere between "promising but unproven" and "you're paying for hope."
This guide is what I actually take, what I stopped taking, and what the evidence supports as of 2026.
Verdict box / Key takeaways
- Creatine monohydrate (3-5g/day) — the most-studied supplement in sports science, with growing evidence for cognitive and bone benefits in older adults.
- Magnesium glycinate (300-400mg) — most Americans are deficient; affects sleep, glucose handling, and cardiovascular markers.
- Omega-3 (EPA+DHA) (2-3g combined) — cardiovascular benefits, inflammation markers, and modest dementia-risk data.
- Vitamin D3 (2,000-5,000 IU based on blood levels) — broad effects on immunity, bone, and mortality risk in deficient populations.
- Oral glutathione (poorly absorbed)
- "Sirtuin activator" branded products
- Senolytics outside of clinical trials
- Most "longevity blends" that combine 12 ingredients at sub-therapeutic doses
- Creatine monohydrate, 5g daily
- Magnesium glycinate, 400mg evening
- Omega-3, 2.4g EPA+DHA daily
- Vitamin D3, 4,000 IU + K2 MK-7
- Tru Niagen (NR), 300mg morning
- Methylene blue (USP grade), 5mg, 3x/week
Total cost: about $95/month. Was higher when I was testing NMN, resveratrol, spermidine, and Ubiquinol together — peaked around $310/month and produced no measurable change in any biomarker I tracked.
The honest summary: if you got the four "high evidence" supplements right and stopped there, you'd capture probably 80% of the achievable benefit. Everything beyond is rounding error or experimentation.
The longevity stack framework: what we're actually optimizing for
Before I list supplements, it's worth being precise about what "longevity" means in this context. The marketing implies you're buying extra years. The reality is more modest.
What we can plausibly influence with supplements:
- Nutrient sufficiency. Filling gaps that diet doesn't reliably cover (D3, omega-3, magnesium for many people).
- Inflammation markers. Things like hs-CRP can shift modestly with omega-3 and lifestyle.
- Muscle mass preservation. This is the single biggest leverage point for healthspan past 40. Creatine and protein are the tools.
- Mitochondrial function. Theoretical for most supplements; better evidence for exercise.
- Sleep quality. Magnesium, glycine — modest but real.
What we probably cannot meaningfully influence with supplements:
- Telomere length (no supplement has shown durable change in well-controlled trials)
- Biological age in the absence of lifestyle changes
- "Cellular senescence" outside of experimental senolytics
If a supplement marketing page promises any of the second category, I'd skip it.
The 4 supplements with the most evidence
Creatine monohydrate
The single supplement with the strongest evidence base, period. There are over 1,000 human studies on creatine, and the safety profile is well-established at 3-5g/day for long-term use (Kreider et al., JISSN 2017).
What the research suggests creatine may support:
- Muscle mass and strength — especially when combined with resistance training. The effect is real but modest (around 1-2kg of added lean mass over 8-12 weeks of training in most trials).
- Cognitive function — particularly under sleep deprivation or stress (Avgerinos et al., 2018).
- Bone health — emerging evidence in postmenopausal women (Chilibeck et al., 2015).
- Mood — small but consistent signal in depression trials.
My personal take: of every supplement I've taken, creatine is the one I'd never give up. My deadlift went up roughly 15 pounds after the first 8 weeks of adding it (training was unchanged). More notably, my morning cognitive sharpness during a brutal 6-week stretch of poor sleep felt subjectively better than it had any right to be.
Dose: 3-5g daily. Loading (20g/day for 5-7 days) is unnecessary unless you want to reach saturation faster.
Form: Monohydrate. Skip the "buffered," "HCl," and "ethyl ester" versions — none have shown superiority to monohydrate at a 5x markup.
[Check Momentous Creatine price -->]
[Check Thorne Creatine on Amazon -->]
Magnesium glycinate
Roughly 50% of Americans don't hit the RDA for magnesium (USDA NHANES data). Magnesium is involved in over 300 enzymatic reactions, including ATP production, glucose handling, and neurotransmitter regulation.
What the research suggests magnesium may support:
- Sleep quality — especially in deficient adults
- Blood pressure — modest reductions in meta-analyses
- Insulin sensitivity — particularly in prediabetic populations
- Migraine prevention (at higher doses than I'd use generally)
I tried magnesium citrate first — gave me reliable GI issues by day 4. Glycinate is gentler and has the added benefit of glycine, which has its own sleep-quality data.
Dose: 300-400mg elemental magnesium, evening with dinner.
Form: Glycinate (also sold as "bisglycinate"). Avoid magnesium oxide — cheap, but absorption is poor enough that it's mostly a laxative.
[Check Pure Encapsulations Magnesium Glycinate price -->]
Omega-3 (EPA + DHA)
The data here is messier than it was a decade ago. The VITAL trial and REDUCE-IT produced conflicting results, but the picture I take from the totality of evidence is: omega-3s in pharmacological doses (2-4g/day combined EPA+DHA) plausibly support cardiovascular markers and brain health, particularly in people whose dietary intake is low.
What omega-3s may support:
- Triglyceride reduction (this one is well-established)
- Inflammation markers like hs-CRP
- Cognitive function in older adults (Yurko-Mauro et al., 2010)
- Mood — modest signal in depression trials
Dose: Aim for 2-3g combined EPA+DHA. Don't read the "fish oil 1,000mg" label — read the back panel for actual EPA+DHA content. A lot of cheap fish oil is 30% active, meaning a 1,000mg capsule has only ~300mg of what you actually want.
Form: Triglyceride form is better absorbed than ethyl esters. I rotate between Carlson's, Nordic Naturals, and Thorne.
Quality matters here more than most categories. Fish oil oxidizes. Buy from brands that publish third-party oxidation testing (IFOS or similar). I've thrown out two bottles in the last three years because they smelled rancid by month 3.
[Check Nordic Naturals Ultimate Omega -->]
Vitamin D3 (with K2)
The case for D3 is strongest when you're actually deficient — which is most people in the northern hemisphere from October through April. Get a 25-hydroxy-D blood test before assuming.
What the research suggests vitamin D may support:
- Bone density (well-established)
- Immune function — modest effect on respiratory infection risk
- All-cause mortality in deficient populations (controversial in sufficient populations)
- Mood in winter — modest
My 25-OH-D ran 22 ng/mL before supplementing. After 6 months at 4,000 IU/day with K2, I was at 48 ng/mL. The target range I aim for is 40-60 ng/mL.
Dose: 2,000-5,000 IU/day depending on baseline. Test, supplement, retest in 3 months.
Form: D3 (cholecalciferol), paired with K2 (MK-7 form) to direct calcium to bone rather than soft tissue.
[Check Thorne D/K2 -->]
The supplements with moderate evidence
This is the tier where I think reasonable, evidence-respecting people can disagree. I take some of these. I've stopped others.
NAD+ precursors (NR and NMN)
The animal data on NAD+ precursors is genuinely impressive. The human data is more modest, mixed, and frankly underwhelming relative to the marketing.
What we know:
- NR (nicotinamide riboside) reliably raises blood NAD+ levels in humans.
- NMN does the same, though it's less well-studied in humans.
- The downstream clinical effects (improved muscle function, metabolic health, etc.) are inconsistent across trials.
- I'm not aware of any human RCT that has shown changes in biological age markers (DNA methylation clocks) from NAD+ precursors.
My personal experience: I ran 500mg/day of NMN for 9 months. I tracked grip strength, VO2max, biological age (TruDiagnostic), and standard blood panels at baseline, 3 months, and 9 months. None of them showed meaningful change. I switched to NR (Tru Niagen) and have stayed there mainly because NR has the cleaner safety record in human trials.
Honest take: I take 300mg NR daily as a low-cost hedge on a plausible-but-unproven mechanism. If I were starting fresh and had a tight budget, I'd skip this category entirely and put the money toward better food.
See my full breakdown: Best NAD+ Supplement: NMN vs NR vs Direct NAD+
Methylene blue
The new darling of biohacker Twitter. The research is interesting — low-dose methylene blue has shown mitochondrial benefits in animal models and some early human cognitive work — but the human longevity data is essentially nonexistent.
What it may support (early evidence):
- Mitochondrial electron transport
- Cognitive performance at very low doses
- Skin/wound healing (topical)
I take 5mg, 3 days a week. USP pharmaceutical grade only — aquarium-grade methylene blue contains heavy metals and is not safe to ingest. This is a place where supplement quality genuinely matters.
Important: Methylene blue interacts dangerously with SSRIs and MAOIs (serotonin syndrome risk). Do not combine without medical guidance.
CoQ10 / Ubiquinol
Modest evidence, particularly in adults over 50 and people on statins (which deplete CoQ10).
What it may support:
- Statin-related muscle pain
- Cardiovascular markers in heart failure (well-studied)
- Mitochondrial function (theoretical)
I tested 200mg/day of ubiquinol for 4 months. Zero perceptible effect on energy, recovery, or any biomarker. I dropped it. I'd reconsider if I were on a statin.
Resveratrol
The supplement that launched the modern longevity industry — and the one whose human data has aged the worst.
The Sinclair-era hype around resveratrol as a sirtuin activator has not held up in human trials. Bioavailability is poor (most oral resveratrol gets metabolized before it does anything). The few human RCTs are mixed at best.
I took 500mg/day for a year. No measurable effect on anything I tracked. I stopped.
Spermidine
Promising mechanism (autophagy induction), some observational human data, no large RCTs. I tried wheat-germ-derived spermidine for 3 months — no detectable effect, expensive. Stopped.
If you eat aged cheese, mushrooms, and wheat germ, you're getting meaningful dietary spermidine without paying $60/month.
The hyped supplements with weak evidence
Oral glutathione
The marketing pitch: glutathione is the "master antioxidant." True. The problem: oral glutathione is broken down in the digestive tract and absorbed minimally. The body makes its own glutathione, and the more useful intervention is providing precursors (NAC, glycine) and the cofactors (selenium, B vitamins).
Skip oral glutathione tablets. Liposomal forms have slightly better absorption claims but the human bioavailability data is still weak.
"Sirtuin activator" branded products
A marketing category, not a scientific one. Anything sold primarily on "activates sirtuins" language is leaning on mechanism, not outcome data. If a product can't point to human outcome data, it's a bet.
Senolytics
Genuinely interesting science. Drugs and compounds like dasatinib + quercetin, fisetin, and others may help clear senescent cells. The animal data is striking. The human data is early-stage — small trials, short follow-up, mixed results.
I do not take senolytics outside of brief, very-low-frequency fisetin experiments (and I'm honestly not sure those did anything). The risk/reward at this stage of the evidence isn't where I want to be.
Trevor's personal stack with rationale
| Supplement | Dose | Timing | Cost/month | Why |
|---|---|---|---|---|
| Creatine monohydrate | 5g | Morning, with coffee | ~$8 | Strongest evidence base of any supplement I take |
| Magnesium glycinate | 400mg | Evening, with dinner | ~$12 | Sleep + filling a likely dietary gap |
| Omega-3 (Nordic Naturals) | 2.4g EPA+DHA | Morning with food | ~$28 | Cardiovascular + inflammation hedge |
| Vitamin D3 + K2 | 4,000 IU D3 / 100mcg K2 | Morning with fat | ~$10 | Was deficient at baseline; retest annually |
| Tru Niagen (NR) | 300mg | Morning | ~$30 | Hedge on the NAD+ mechanism; clean safety profile |
| Methylene blue (USP) | 5mg, 3x/week | Mid-morning | ~$5 | Experimental; mitochondrial mechanism |
| Total | ~$93/month |
What I don't take that you might expect:
- A multivitamin (I'd rather get specific nutrients I'm actually deficient in)
- NMN (no measurable benefit over 9 months at 500mg)
- Resveratrol (human evidence didn't pan out)
- CoQ10 (I'm not on a statin and felt nothing)
- Berberine (interesting metabolic data, but I prefer to drive glucose handling with diet + creatine + zone 2)
- Sirtuin "activator" products (marketing, not science)
How to evaluate a supplement brand
The supplement industry is regulated less stringently than most people assume. The FDA does not pre-approve supplements. Independent testing has repeatedly found products that don't contain what they claim, are contaminated, or are spiked with undeclared ingredients (JAMA, 2013; ConsumerLab reports).
What to look for:
- Third-party testing. Look for NSF Certified for Sport, USP Verified, Informed-Sport, or ConsumerLab approval. These programs actually test contents and contaminants.
- Certificate of Analysis (COA) availability. Reputable brands publish COAs by lot or make them available on request.
- GMP certification. Good Manufacturing Practices — minimum bar, not a high bar.
- Transparent dosing. Avoid "proprietary blends" that hide individual ingredient doses behind a total weight.
- Reasonable claims. If the label promises to reverse aging, walk away.
What to be skeptical of:
- "Doctor formulated" (anyone can hire a doctor)
- "Clinically proven" (proven for what? at what dose? in whom?)
- Celebrity endorsements (no comment needed)
- Free trial / subscription traps (the business model says everything)
Best brands by category
These are the brands I actually buy from, ranked by category. I have no exclusive affiliate relationships influencing this list — these are the ones that consistently pass independent testing and that I keep going back to.
| Category | Brand | Why |
|---|---|---|
| All-around quality | Thorne | NSF certified, transparent COAs, broad range |
| Premium / clean labels | Momentous | NSF Certified for Sport on most products |
| Practitioner brand | Pure Encapsulations | Hypoallergenic, clean excipients |
| Functional medicine staple | Designs for Health | Well-formulated, used by clinicians |
| Fish oil specialist | Nordic Naturals | Third-party oxidation testing |
| NAD+ category | Tru Niagen | Most human safety data of any NR product |
Affiliate links:
- [Check Thorne on Amazon -->]
- [Check Momentous price -->]
- [Check Pure Encapsulations on Amazon -->]
- [Check Designs for Health -->]
- [Check Nordic Naturals -->]
- [Check Tru Niagen -->]
What to do BEFORE starting a stack: baseline blood work
This is the part most supplement guides skip, and it's the part with the highest leverage. Without baseline data, you can't tell if you're treating a real deficiency or just generating expensive urine.
The panel I recommend (and pulled myself before starting):
- Standard CBC + CMP — kidney, liver, electrolytes
- Lipid panel with ApoB — better cardiovascular marker than LDL alone
- hs-CRP — inflammation
- HbA1c + fasting glucose + fasting insulin — glucose handling
- 25-OH Vitamin D
- Magnesium RBC (more accurate than serum)
- Omega-3 index (if you can get it — most can't through standard labs)
- Ferritin + iron panel
- TSH + free T4 — thyroid baseline
- B12 + folate + homocysteine
- Testosterone (total + free) for men over 35, especially
Cost out-of-pocket via Quest or Labcorp direct: typically $250-400 for the bundle. Ulta Lab Tests, Marek Health, and Function Health all offer comprehensive bundles.
Why this matters: I added vitamin D and magnesium because I was deficient. I dropped iron because my ferritin was 220 (high). I changed nothing about my B12 because it was already 700. Without the labs, I would have guessed wrong on at least two of those.
Stack timing: morning vs evening, with food vs without
| Supplement | When | Why |
|---|---|---|
| Creatine | Anytime | Saturation-based; timing irrelevant once you're loaded |
| Magnesium glycinate | Evening | Mild relaxation effect; pairs with sleep |
| Omega-3 | With largest fatty meal | Fat-soluble; reduces fish burps |
| Vitamin D3 / K2 | With a fatty meal | Fat-soluble; better absorbed |
| NR / NMN | Morning | Some users report mild stimulation |
| Methylene blue | Mid-morning | Avoid evening — can disrupt sleep |
| Caffeine | Morning | Half-life is roughly 6 hours; avoid late |
Don't take everything with everything. Calcium, iron, zinc, and magnesium can compete for absorption. I keep magnesium separate from other minerals.
The supplements I stopped taking and why
A partial autopsy of my supplement graveyard:
- NMN (500mg/day, 9 months) — no measurable benefit on biomarkers I tracked; switched to NR.
- Resveratrol (500mg/day, 12 months) — poor bioavailability; human evidence is weak.
- CoQ10 / Ubiquinol (200mg/day, 4 months) — no perceptible effect; I'm not on a statin.
- Spermidine (1mg/day, 3 months) — interesting mechanism, no perceptible effect, dietary sources cheaper.
- Berberine (1,500mg/day, 6 months) — modest fasting glucose drop, but GI side effects didn't justify it.
- Curcumin (500mg/day, 5 months) — no perceptible effect on joints or markers. Might revisit a more bioavailable form.
- Lion's mane (1g/day, 4 months) — nothing detectable. Maybe placebo would have helped if I'd believed harder.
- A high-end multivitamin — replaced with targeted single ingredients informed by blood work.
The pattern: "interesting mechanism, no detectable effect over months of use" is the most common outcome. That's worth knowing.
YMYL disclaimer
RecoveryStack is not medical advice. I'm an n=1 hobbyist who reads papers and tracks my own data — not a physician. Talk to your doctor before starting any supplement regimen, especially if you take prescription medications or have a health condition. Some supplements interact dangerously with medications (methylene blue + SSRIs, vitamin K + warfarin, magnesium + certain blood pressure meds, fish oil + blood thinners). Pregnancy, kidney disease, and liver disease all change the calculus for supplement safety. Get baseline labs. Re-test. Adjust.
FAQ
If I had to pick one, creatine. It has the deepest research base, the cleanest safety profile, and the most plausible cross-domain benefits (muscle, bone, cognition).
No. No supplement has been shown to extend human lifespan in a properly controlled trial. Some support healthspan and biomarkers; that's a different and more modest claim.
Probably not, given the current evidence. NR has more human safety and efficacy data. NMN has more marketing.
For most supplements, 8-12 weeks at the labeled dose with a clear before/after biomarker comparison.
Most are compatible, but check interactions and avoid stacking multiple supplements that hit the same mechanism (e.g., don't take three different "sleep stacks" at once).
For the four high-evidence supplements above, no. For methylene blue and stimulant-like compounds, periodic breaks are reasonable.
Generally lower-dose and contain more sugar/fillers. Fine for creatine if the dose checks out; less ideal for D3 or omega-3.
Out of scope for this guide. Different regulatory and safety category — not a supplement question.
I don't, and most evidence-based clinicians I respect don't either. Target specific deficiencies based on blood work.
$60-120/month for the high-evidence core. More than $200/month means you're either at the cutting edge or being marketed to.
Mostly no. The "personalization" is usually a quiz that nudges you toward higher-margin products. Run blood work, build your own stack, save money.
Urolithin A (mitochondrial autophagy), GlyNAC (glycine + NAC for glutathione), and rapamycin (drug, not supplement) are the three with the most interesting active research.
Related articles
- Best Creatine for Women (2026)
- Best NAD+ Supplement: NMN vs NR vs Direct NAD+ Tested (2026)
- The Beginner's Guide to Zone 2 Cardio
- How I Track My Biological Age (and What Actually Moved It)
Author bio
Trevor Kaak is the founder of RecoveryStack. He's spent three years and around $4,200 testing longevity supplements, gear, and protocols on himself. He runs baseline blood panels twice a year, lifts heavy four days a week, and is professionally suspicious of any longevity claim that doesn't survive a real human trial. Reach him at trevor@recoverystack.co.