Anti-Aging Supplements Every Man Over 40 Should Consider

The New Era of Men’s Health

Aging is no longer seen as an inevitable decline. For men over 40, the goal has shifted from merely “staying healthy” to actively optimizing biology for peak performance and longevity. This is the biohacking revolution.

In this guide, we break down the most potent, science-backed supplements that can help slow down the biological clock, improve energy levels, and sharpen cognitive function. We focus on compounds that target the hallmarks of aging: cellular senescence, mitochondrial dysfunction, and genomic instability.

Disclaimer: Always consult with a healthcare professional before starting any new supplement regimen, especially if you have underlying health conditions.

1. NMN (Nicotinamide Mononucleotide)

The NAD+ Booster

As we age, our levels of NAD+ (Nicotinamide Adenine Dinucleotide) plummet. By age 50, you may have half the NAD+ levels you had in your 20s. NAD+ is critical for cellular energy production and DNA repair.

Why It Matters

NMN is a direct precursor to NAD+. Supplementing with NMN has been shown in studies to restore NAD+ levels, which can lead to:

Increased Energy: Improved mitochondrial function leading to better ATP production
Better DNA Repair: Enhanced activity of sirtuins (longevity genes)
Improved Insulin Sensitivity: Better metabolic health and glucose regulation
Enhanced Vascular Function: Improved blood flow and endothelial health

The Science

Recent human trials have demonstrated that NMN supplementation can increase NAD+ levels by up to 40% in just 4 weeks. The compound is absorbed rapidly in the small intestine and converted to NAD+ within 15 minutes of ingestion.

Timing and Absorption

Take NMN sublingually (under the tongue) for maximum absorption, or take it with water on an empty stomach in the morning. Some users split their dose between morning and early afternoon to maintain stable NAD+ levels throughout the day.

Recommended Dosage: 500mg - 1000mg daily, taken in the morning. Start with 250mg and gradually increase to assess tolerance.

Top Picks:

Renue By Science Lipo NMN (Liposomal for high bioavailability)
ProHealth NMN Pro (Third-party tested, pharmaceutical grade)

Cost: Expect to pay $50-80/month for quality NMN.

2. Resveratrol

The Sirtuin Activator

Often famously associated with red wine, Resveratrol is a potent antioxidant that mimics the effects of calorie restriction. It works synergistically with NMN to create what Dr. David Sinclair calls the “longevity stack.”

Why It Matters

Resveratrol activates SIRT1, a gene that protects the body against diseases of aging. It acts as the “accelerator pedal” for sirtuins, while NAD+ is the fuel.

Cardiovascular Health: Improves blood flow, reduces LDL oxidation, and decreases inflammation
Neuroprotection: May protect against cognitive decline and support BDNF (brain-derived neurotrophic factor)
Metabolic Health: Improves insulin sensitivity and may activate AMPK pathways
Cellular Cleaning: Promotes autophagy, the body’s natural cellular cleanup process

The Trans-Resveratrol Difference

Only Trans-Resveratrol (not Cis-) is bioactive. Most supplements contain only 50% Trans-Resveratrol, so check labels carefully. Look for 98%+ purity.

Absorption Hack

Resveratrol has notoriously poor bioavailability. Take it with:

A source of fat (yogurt, olive oil, or piperine/black pepper extract)
Quercetin (enhances absorption)
On an empty stomach if using micronized formulations

Recommended Dosage: 500mg - 1000mg daily of Trans-Resveratrol, ideally with a fat source for absorption.

Stacking: Best taken with NMN in the morning. Some users add Pterostilbene (a methylated form of resveratrol) for enhanced bioavailability.

3. Vitamin D3 & K2

The Hormonal Foundation

Most men over 40 are deficient in Vitamin D, which is actually a pro-hormone, not just a vitamin. Studies show that over 70% of men have suboptimal levels below 30 ng/mL.

Why It Matters

Vitamin D is essential for testosterone production, immune function, and bone health. However, taking D3 without K2 can be dangerous, as K2 ensures calcium is deposited in bones and not arteries.

Testosterone Support: Optimal levels (50-80 ng/mL) are linked to healthy T levels
Heart Health: Vitamin K2 prevents arterial calcification
Immune Function: Critical for innate and adaptive immunity
Mood Regulation: Deficiency linked to depression and cognitive decline
Muscle Strength: Supports protein synthesis and muscle function

The K2 Connection

Vitamin K2 (specifically MK-7) activates proteins that regulate calcium. Without K2, supplemental D3 can paradoxically increase cardiovascular risk by depositing calcium in arteries instead of bones.

Testing and Optimization

Get your 25-hydroxyvitamin D levels tested. Target range:

Minimum: 40 ng/mL
Optimal for performance: 50-80 ng/mL
Upper safe limit: 100 ng/mL

Recommended Dosage:

5000 IU of D3 + 100-200mcg of K2 (MK-7) daily
Higher doses (10,000 IU) may be needed initially if severely deficient
Take with a fatty meal for absorption

When to Test: Retest after 3 months, then every 6 months once optimal levels are achieved.

4. Magnesium

The Master Mineral

Magnesium is involved in over 600 enzymatic reactions in the body. Stress, alcohol, and heavy training deplete it rapidly. An estimated 50% of Americans are deficient.

Why It Matters

Sleep Quality: Critical for deep, restorative sleep by regulating GABA receptors
Muscle Recovery: Reduces cramps and aids relaxation by regulating calcium channels
Heart Rhythm: Maintains healthy blood pressure and prevents arrhythmias
Stress Response: Modulates the HPA axis and cortisol production
Bone Health: 60% of the body’s magnesium is stored in bones
Blood Sugar: Improves insulin sensitivity

Form Matters

Not all magnesium is created equal:

Magnesium Glycinate: Best for sleep and relaxation. Highly absorbable, doesn’t cause digestive upset. Take before bed.

Magnesium Threonate: Crosses the blood-brain barrier. Best for cognitive function and neuroprotection. More expensive but worth it for brain health.

Magnesium Citrate: Good absorption but can have a laxative effect. Use for constipation.

Avoid: Magnesium Oxide (poor absorption, only 4%)

Timing Strategy

Split your dose:

Morning: 200mg Threonate (cognitive benefits)
Evening: 200-400mg Glycinate (sleep quality)

Recommended Dosage: 400-600mg daily total, preferably split between forms. Take Glycinate or Threonate before bed for sleep benefits.

Signs of Deficiency: Muscle cramps, poor sleep, anxiety, irregular heartbeat, fatigue.

5. Omega-3 Fatty Acids (EPA/DHA)

The Anti-Inflammatory Powerhouse

Chronic inflammation is a primary driver of aging (“inflammaging”). High-quality fish oil is your best defense against this silent killer.

Why It Matters

Brain Health: DHA is a major structural component of the brain (40% of brain fat)
Joint Health: Reduces stiffness and pain from inflammation
Heart Health: Lowers triglycerides by up to 30% and reduces cardiovascular risk
Mental Health: EPA shows antidepressant effects in clinical trials
Muscle Protein Synthesis: Enhances anabolic response to training
Eye Health: DHA is concentrated in the retina

The Quality Problem

Most fish oils on the market are oxidized (rancid) or contaminated with mercury, PCBs, and other toxins. This does more harm than good.

What to Look For

IFOS 5-Star Certification: Independent testing for purity and potency
Triglyceride Form: More bioavailable than ethyl ester form
Freshness: Check the peroxide value (should be <5 meq/kg)
Concentration: Look for high EPA+DHA per capsule (500mg+ combined)
Sustainable: MSC certified for ocean health

EPA vs DHA

EPA (Eicosapentaenoic acid): Better for inflammation, mood, cardiovascular health
DHA (Docosahexaenoic acid): Better for brain structure, cognition, vision

For anti-aging: aim for a 2:1 EPA:DHA ratio or balanced 1:1.

Dosage Based on Goals

Maintenance: 2g combined EPA/DHA
High Inflammation: 3-4g combined
Triglyceride Reduction: 4-6g (medical supervision)

When to Take: With a fatty meal for absorption. Consider splitting dose (morning and evening) for better utilization.

Top Picks:

Nordic Naturals Ultimate Omega (Consistently ranked highest purity)
Carlson Elite Omega-3 (IFOS certified, affordable)
SPM Active (Specialized pro-resolving mediators for advanced users)

Cost: $30-50/month for pharmaceutical-grade fish oil.

Advanced Stack: The Longevity Protocol

For men serious about optimization, consider this comprehensive stack:

Morning (Fasted)

NMN: 500-1000mg (sublingual)
Resveratrol: 500mg (with olive oil)
Vitamin D3: 5000 IU + K2: 200mcg
Omega-3: 2g

Afternoon (with lunch)

Alpha-Lipoic Acid: 300mg (mitochondrial support)
Coenzyme Q10: 200mg (if over 50)

Evening (before bed)

Magnesium Glycinate: 400mg
Apigenin: 50mg (from parsley or chamomile extract)

Cost Estimate

Total monthly cost for complete stack: $150-200

Biomarker Testing

Don’t supplement blindly. Get these tests done:

Essential Baseline

Vitamin D (25-hydroxyvitamin D)
Omega-3 Index (target: >8%)
hsCRP (high-sensitivity C-Reactive Protein for inflammation)
Homocysteine (methylation status)
Complete Blood Count

Advanced Optimization

NAD+ levels (specialized test)
Biological age tests (TruDiagnostic, Elysium Index)
Advanced lipid panel (LDL-P, Apo B)

Retest every 6-12 months to track progress.

Conclusion: The Synergy Effect

Taking one of these supplements alone is good, but the real magic happens when they are combined into a comprehensive strategy. NMN fuels the engine, Resveratrol hits the gas, and Vitamin D/Omega-3 build a resilient chassis.

Implementation Strategy

Week 1-2: Start with the basics

Vitamin D3+K2
Magnesium
Omega-3

Week 3-4: Add foundational support

Test and adjust dosages based on how you feel
Get baseline blood work

Month 2: Layer in longevity molecules

NMN (start low, 250mg)
Resveratrol

Month 3+: Optimize and refine

Adjust based on biomarker results
Add advanced compounds if desired

Start with the basics (D3, Magnesium, Omega-3), then layer in the advanced longevity molecules (NMN, Resveratrol) as you optimize your routine. Track your progress with subjective markers (energy, sleep, recovery) and objective data (blood work).

Your future self will thank you.

References and Further Reading

Yoshino et al. (2021) - NAD+ intermediates and aging
Sinclair, D. (2019) - Lifespan: Why We Age - and Why We Don’t Have To
Omega-3 Index: www.omega3index.com
Examine.com - Supplement Database
IFOS Testing: www.ifosprogram.com