Anti-Aging Supplements: A Physician's Actual Stack for Longevity

At a Glance

The anti-aging supplement market is worth over $60 billion globally, and it is growing at roughly 8% per year. For every compound with genuine human evidence behind it, there are a dozen marketed on animal studies, mechanistic speculation, or influencer endorsement. The result is that most people spending serious money on anti-aging supplements are taking things that have never been shown to slow aging in humans.

I want to be honest about something. As a physician who treats patients six days a week at a hospital, I am in a different position than most people writing about anti-aging supplements online. I see blood work. I see outcomes. I see what happens when patients come in after spending $500 a month on a supplement stack they assembled from podcast recommendations — and their vitamin D is still at 22 ng/mL because nobody checked.

Here is what I actually take, what I recommend to my patients, and — just as importantly — what I have stopped recommending as the evidence has matured.

The Foundation: Labs Before Supplements

Before I discuss any specific compound, this needs to be stated plainly: supplementing without knowing your baseline levels is guessing. And guessing with your health is not a strategy.

The minimum lab panel I run before designing any longevity supplement protocol includes:

• 25-OH Vitamin D — the single most commonly deficient nutrient in my patient population
• RBC Magnesium — serum magnesium misses intracellular deficiency in roughly 50% of cases
• Omega-3 Index — measures EPA/DHA content in red blood cell membranes; target is 8-12%
• hs-CRP — baseline systemic inflammation marker
• Fasting insulin and HbA1c — metabolic health baseline
• Homocysteine — methylation status; indicates B-vitamin needs
• Ferritin — iron storage; both deficiency and excess are problems for aging
• CoQ10 plasma levels — especially relevant in patients over 40 or on statins

What I tell my patients: if someone is selling you an anti-aging supplement without first checking your blood work, they are selling you a product, not healthcare.

Tier 1: Strong Evidence — What I Take Daily

Vitamin D3 (5,000 IU/day, titrated to labs)

Evidence level: Strong

Vitamin D is not glamorous. It does not trend on social media. But it is the single most impactful supplement for the majority of my patients, because the majority of my patients are deficient.

In clinical practice, I target serum 25-OH vitamin D levels of 50-70 ng/mL. This is higher than the conventional “sufficient” threshold of 30 ng/mL, and it is based on evidence from multiple domains:

• Immune function: Vitamin D modulates both innate and adaptive immunity. Deficiency is associated with increased susceptibility to infection and autoimmune dysregulation [1].
• Cardiovascular risk: A 2022 Mendelian randomization study in the European Heart Journal demonstrated that genetically predicted vitamin D levels below 50 nmol/L were causally associated with increased cardiovascular mortality [2].
• Cancer risk: The VITAL trial (25,871 participants, 5.3 years) found that vitamin D supplementation reduced cancer mortality by 25% in the per-protocol analysis, though the primary endpoint of cancer incidence was not met [3].
• Musculoskeletal health: Adequate vitamin D is essential for calcium absorption, bone density maintenance, and muscle function — all critical for aging well.

My protocol: 5,000 IU vitamin D3 daily with a fat-containing meal. I combine this with vitamin K2 (MK-7, 200 mcg) to direct calcium to bone rather than arteries. I recheck levels every 3-4 months until stable, then annually.

The caveat: Vitamin D is dose-dependent and individual. Some patients need 2,000 IU. Others need 10,000 IU. The dose that gets your blood to 50-70 ng/mL is the right dose. This is why labs are not optional.

Omega-3 (2,400 mg EPA/DHA daily)

Evidence level: Strong

I covered omega-3 dosing for inflammation in detail in my omega-3 dosage article, so I will focus on the anti-aging rationale here.

The anti-aging case for omega-3 rests on two pillars:

1. Telomere length preservation. Farzaneh-Far et al. published landmark data in JAMA showing that higher omega-3 blood levels were associated with slower telomere shortening over 5 years in patients with coronary artery disease [4]. This was observational, but the dose-response relationship was robust.
2. Chronic low-grade inflammation reduction. Inflammaging — the slow, persistent elevation of inflammatory markers with age — is considered a primary driver of aging-related disease. Omega-3 supplementation at 2,000+ mg/day reliably reduces hs-CRP, IL-6, and TNF-alpha.

My protocol: 2,400 mg combined EPA/DHA per day, EPA-dominant ratio (roughly 1,600 mg EPA / 800 mg DHA). I use a triglyceride-form fish oil. I verify with an Omega-3 Index test — if the index is below 8%, I increase the dose.

Magnesium (400 mg elemental, evening)

Evidence level: Strong

Magnesium is involved in over 600 enzymatic reactions. Deficiency is endemic — estimates suggest 50-80% of the Western population has inadequate magnesium intake. Serum magnesium is a poor marker because only 1% of total body magnesium is in the blood; this is why I order RBC magnesium.

For aging specifically:

• DNA repair: Magnesium is a cofactor for DNA polymerase and multiple DNA repair enzymes. Deficiency accelerates genomic instability — one of the hallmarks of aging [5].
• Mitochondrial function: ATP exists as magnesium-ATP in the cell. Without adequate magnesium, mitochondrial energy production is impaired.
• Sleep quality: Magnesium glycinate or threonate improves sleep architecture in multiple trials. Sleep quality is arguably the single most important modifiable factor in biological aging.
• Cardiovascular protection: A meta-analysis of 40 prospective cohort studies found that each 100 mg/day increase in magnesium intake was associated with a 22% reduction in heart failure risk and an 11% reduction in stroke risk [6].

My protocol: 400 mg elemental magnesium as magnesium glycinate in the evening. For patients with cognitive concerns, I add magnesium L-threonate (2,000 mg), which crosses the blood-brain barrier more effectively.

Tier 2: Moderate Evidence — Conditionally Recommended

Coenzyme Q10 (200 mg/day)

Evidence level: Moderate

CoQ10 is essential for mitochondrial electron transport chain function — specifically Complex III. Endogenous production declines measurably after age 40, and statin drugs further suppress CoQ10 synthesis by inhibiting the mevalonate pathway (the same pathway that produces cholesterol).

The human evidence for CoQ10 supplementation:

• Heart failure: The Q-SYMBIO trial (420 patients, 2-year follow-up) demonstrated that 300 mg/day CoQ10 reduced major adverse cardiovascular events by 43% and cardiovascular mortality by 42% in patients with chronic heart failure [7].
• Statin myopathy: Multiple trials confirm that CoQ10 supplementation (100-200 mg/day) reduces statin-associated muscle pain and weakness, though results are not uniform across all studies.
• Exercise performance in older adults: A 2018 RCT showed that CoQ10 supplementation improved exercise tolerance and reduced oxidative stress markers in healthy older adults.
• Mitochondrial function: Mechanistic evidence is strong — CoQ10 is directly involved in mitochondrial ATP production. Whether supplementation meaningfully increases intracellular CoQ10 in all tissues remains debated, but ubiquinol (the reduced form) appears to have better bioavailability than ubiquinone.

My protocol: 200 mg ubiquinol daily with a fat-containing meal. I consider this essential for anyone over 40 and non-negotiable for anyone on a statin.

NAD+ Precursors (Periodic, Protocol-Dependent)

Evidence level: Moderate

I wrote extensively about the NAD+ IV vs NMN vs NR comparison elsewhere. For the purposes of an anti-aging stack, here is my current position:

NAD+ decline with age is well-documented. The question has always been whether exogenous NAD+ repletion — by any route — translates to meaningful anti-aging effects in humans. The answer, as of 2026, is: probably, but the definitive long-term human data is still accumulating.

What I do in practice:

• NAD+ IV: I use periodic IV NAD+ infusions (250-500 mg) as part of intensive treatment protocols, particularly for patients with significant fatigue, post-infectious syndromes, or cognitive decline. This is clinical, not daily supplementation.
• NMN oral: For daily NAD+ support, I currently favor NMN at 500 mg/day based on the growing human RCT data showing dose-dependent NAD+ elevation and improvements in physical performance metrics.
• Cycling: I cycle NMN — 3 months on, 1 month off — because we do not have long-term continuous-use safety data, and precautionary cycling is prudent when the evidence base is still maturing.

What I do not do: I do not take high-dose NAD+ precursors continuously without monitoring. NAD+ metabolism feeds into pathways (PARP, CD38, sirtuins) with complex downstream effects, and more is not necessarily better.

Vitamin K2 (MK-7, 200 mcg/day)

Evidence level: Moderate

K2 activates matrix Gla protein (MGP) and osteocalcin — the first directs calcium away from arterial walls, the second directs it to bone. The anti-aging rationale is vascular calcification prevention, which is one of the most reliable predictors of cardiovascular aging.

The Rotterdam Study found that high dietary vitamin K2 intake was associated with a 57% reduction in cardiovascular mortality over 7-10 years [8]. Supplementation data is more limited but directionally consistent. I consider K2 a logical companion to vitamin D3 supplementation and include it as a default.

Tier 3: Overhyped or Insufficient Evidence

Resveratrol — The Uncomfortable Truth

I need to be direct about this because resveratrol remains one of the most popular anti-aging supplements sold, and the narrative around it is largely built on outdated science.

The resveratrol story began with David Sinclair’s 2003 Nature paper showing that resveratrol activated sirtuins and extended lifespan in yeast. Subsequent studies in mice showed metabolic improvements at high doses. The supplement industry took off.

Here is what actually happened in humans:

• Bioavailability is poor. Oral resveratrol undergoes extensive first-pass metabolism. Plasma levels after supplementation are a tiny fraction of the concentrations used in cell and animal studies.
• Human RCTs have been largely disappointing. The REMUS trial found no effect on metabolic parameters in obese men. Multiple cardiovascular trials have failed to show benefit. A 2014 JAMA Internal Medicine study in an Italian cohort found no association between urinary resveratrol metabolites and longevity, cardiovascular disease, or cancer incidence.
• The sirtuin activation story has been complicated. The original mechanism (direct SIRT1 activation) has been questioned. Resveratrol may activate SIRT1 indirectly through AMPK, but at the concentrations achievable with oral supplementation, this effect is minimal.

My position: I stopped recommending resveratrol to patients roughly two years ago. The animal data was exciting. The human data has not delivered. If you are currently taking resveratrol, I am not saying it is harmful — at standard doses (250-500 mg), it is well tolerated. I am saying the evidence does not justify the cost or the confidence with which it is marketed.

Pterostilbene — Slightly More Promising, Still Limited

Pterostilbene is often positioned as “resveratrol 2.0” because of its superior bioavailability (approximately 4x that of resveratrol) and longer half-life. The mechanistic rationale is similar — SIRT1 activation, AMPK pathway engagement, antioxidant effects.

The human data remains limited. There are small trials showing lipid-lowering effects and improved blood pressure, but nothing approaching the evidence base for the Tier 1 or Tier 2 compounds. I am watching the literature but not currently recommending it as a core stack component.

Collagen Peptides — Context-Dependent

Collagen supplementation has moderate evidence for skin elasticity (improvement in dermal collagen density after 8-12 weeks of hydrolyzed collagen at 5-10 g/day) and limited evidence for joint support. As an anti-aging supplement in the biological aging sense — targeting the hallmarks of aging — the evidence is weak. Collagen is a cosmetic and structural support supplement, not a longevity supplement. They are different categories.

The Supplements I Am Watching

Several compounds are in early-stage human research with promising but insufficient data for routine recommendation:

• Fisetin: A senolytic flavonoid with encouraging preclinical data for clearing senescent cells. Human trials are underway (the AFFIRM trial at Mayo Clinic). I covered this in my fisetin article. Evidence level: emerging.
• Spermidine: Autophagy-inducing polyamine that inhibits EP300 acetyltransferase and activates TFEB — effectively mimicking key aspects of caloric restriction at the cellular level. Observational data links higher dietary intake to reduced all-cause mortality, and a 12-month RCT (SPORT trial) found improved memory composite scores and reduced inflammatory markers in older adults at risk for dementia. Evidence level: moderate-emerging. I covered the full mechanism, dosing, and stacking rationale in the spermidine longevity deep dive.
• Urolithin A (Mitopure): Mitophagy activator with published human data showing improved mitochondrial function and exercise performance. The ATLAS trial was positive but industry-sponsored. Evidence level: moderate-emerging.

I do not include these in my current stack, but I may within the next 1-2 years as the evidence matures.

What the Complete Stack Looks Like

Here is my actual daily protocol, with approximate costs:

This is not a glamorous stack. There is no exotic compound from a remote jungle. There is no proprietary blend with a trademarked name. It is boring — and that is the point. The compounds with the strongest human evidence for longevity-relevant outcomes are, with the exception of NMN, well-established and relatively inexpensive.

The Things That Matter More Than Supplements

I would be negligent if I did not say this clearly: supplements are the 20% after you have addressed the 80%.

The 80% is:

• Sleep: 7-8 hours of quality sleep with adequate deep sleep and REM architecture. No supplement compensates for chronic sleep deprivation. None.
• Exercise: Zone 2 cardiovascular training (150+ minutes/week), resistance training (2-3x/week), and VO2 max optimization. Exercise is the single most powerful longevity intervention that exists.
• Metabolic health: Maintaining insulin sensitivity through diet and activity. Fasting insulin below 5 mU/L, HbA1c below 5.3%.
• Stress management and social connection: Chronic psychological stress accelerates biological aging through cortisol-mediated telomere shortening and inflammatory activation.
• Diet: Adequate protein (1.2-1.6 g/kg), diverse plant intake for polyphenols and fiber, minimized ultra-processed food.

If you are sleeping 5 hours, not exercising, and eating primarily processed food, spending $200 a month on supplements is not an anti-aging strategy. It is an expensive distraction from the interventions that would actually change your trajectory.

A Note on Supplement Quality

Not all supplements are created equal. The supplement industry has minimal regulatory oversight compared to pharmaceuticals, and quality varies enormously. What I look for:

• Third-party testing: NSF, USP, or Informed Sport certification. At minimum, a certificate of analysis (COA) from an independent lab.
• Bioavailable forms: Ubiquinol over ubiquinone for CoQ10. Triglyceride-form over ethyl ester for omega-3. Glycinate, threonate, or malate for magnesium — not oxide.
• Transparent labeling: No proprietary blends where you cannot see individual doses.
• GMP manufacturing: Good Manufacturing Practice certification at minimum.

When patients ask me for specific brand recommendations, I give them criteria rather than brands, because brands change and quality can drift. The criteria above have not failed me yet.

References

1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
2. Sofianopoulou E, Kaptoge SK, Afzal S, et al. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses. Lancet Diabetes Endocrinol. 2022;10(6):e4.
3. Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33-44.
4. Farzaneh-Far R, Lin J, Epel ES, et al. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA. 2010;303(3):250-257.
5. Killilea DW, Maier JA. A connection between magnesium deficiency and aging: new insights from cellular studies. Magnes Res. 2008;21(2):77-82.
6. Fang X, Wang K, Han D, et al. Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. BMC Med. 2016;14(1):210.
7. Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO — a randomized double-blind trial. JACC Heart Fail. 2014;2(6):641-649.
8. Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004;134(11):3100-3105.