I am frequently asked which supplements I recommend and personally use. I typically take a core group at least five days per week and allow two days off. These compounds are selected to target mitochondrial decline, chronic inflammation, cellular senescence, vascular aging, and the progressive drop in NAD+ levels that occurs over time.
For context, NAD+ levels decline by approximately 50 percent every 20 years. Chronic low-grade inflammation, often called inflammaging, is strongly associated with cardiovascular disease, neurodegeneration, metabolic syndrome, and frailty. My strategy is to address these upstream drivers rather than isolated symptoms.
Over time, I have monitored biological markers including intracellular NAD+ and Klotho. My NAD+ levels have tested within ranges typically seen in much younger individuals, and my Klotho levels have placed in the 90th percentile compared with males aged 18 to 35. While no single marker defines biological age, these data points support the value of a structured lifestyle and supplementation approach.
The Top 15 Supplements
1. Resveratrol or Pterostilbene
Activates SIRT1, a longevity-associated sirtuin involved in DNA repair and metabolic regulation. Pterostilbene offers improved bioavailability. These compounds also provide antioxidant and anti-inflammatory support.
2. Curcumin
Activates NRF2, the master regulator of endogenous antioxidant defenses. NRF2 influences hundreds of genes involved in detoxification and oxidative stress reduction. Curcumin is a central tool in slowing inflammaging.
3. Coenzyme Q10
Essential for mitochondrial ATP production within the electron transport chain. Levels decline with age and are reduced further in statin users. Supports cardiac output and reduces oxidative stress.
4. Nicotinamide Riboside, NMN, or NAD+
Precursors that raise NAD+, supporting DNA repair enzymes such as PARPs and sirtuins. Given the progressive decline of NAD+ over decades, replenishment is a central longevity strategy. I pair NAD+ support with trimethylglycine to preserve methylation capacity.
5. Spermidine
Stimulates autophagy, the cellular cleanup process that removes damaged proteins and organelles. Autophagy efficiency declines significantly with age, and spermidine mimics some effects of caloric restriction.
6. Urolithin A
Promotes mitophagy, the selective removal of dysfunctional mitochondria. Many individuals cannot efficiently produce urolithin A from dietary sources. Clinical studies show improvements in muscle endurance and mitochondrial health.
7. Fisetin
A senolytic compound that helps clear senescent cells. Senescent cells secrete pro-inflammatory cytokines and contribute to tissue dysfunction. Removing these cells may reduce systemic inflammatory burden.
8. Alpha-Lipoic Acid
A universal antioxidant that regenerates vitamins C and E and replenishes glutathione. Also improves insulin sensitivity and has demonstrated benefit in diabetic neuropathy.
9. Nitric Oxide Support
Nitric oxide production declines with age, impairing vascular flexibility and blood flow. Supporting NO improves endothelial function, exercise tolerance, and stem cell mobilization.
10. Berberine
Activates AMPK, often referred to as the metabolic master switch. Improves glucose control, lipid metabolism, and insulin sensitivity. Frequently compared to metformin for metabolic support.
11. Omega-3 Fatty Acids
EPA and DHA reduce inflammatory cytokine production and support cell membrane integrity. Chronic inflammation underlies most age-related diseases, making omega-3 intake foundational.
12. Green Tea Extract (EGCG)
A potent antioxidant that influences metabolic regulation, cardiovascular health, and hepatic protection. Also interacts with cellular stress response pathways.
13. Trimethylglycine (TMG)
A methyl donor that supports homocysteine regulation and epigenetic balance. Essential when using NAD+ precursors to prevent methyl depletion.
14. Vitamin D3
Vitamin D functions more like a hormone than a vitamin. Regulates hundreds of genes affecting bone density, immune balance, muscle strength, and inflammatory control. Deficiency correlates with increased frailty and chronic disease risk.
15. GlyNAC
A combination of glycine and N-acetylcysteine that restores glutathione, the body’s master antioxidant. Human and animal studies show improvements in mitochondrial function, oxidative stress, strength, and metabolic markers. In animal models, lifespan extension of approximately 20 to 25 percent has been observed.
Key Pathways and Targets
Collectively, these supplements influence core longevity pathways including:
- Sirtuin activation
- NRF2 antioxidant signaling
- NAD+ biosynthesis
- AMPK metabolic regulation
- Autophagy and mitophagy
- Senolytic clearance
- Nitric oxide signaling
- Methylation balance
- Glutathione restoration
The objective is not reliance on a single compound, but coordinated support of multiple interconnected aging mechanisms.
The Most Important Anti-Aging Intervention: Exercise
No supplement replaces exercise. Physical activity directly improves mitochondrial density, insulin sensitivity, nitric oxide production, and inflammatory balance. Many of the pathways targeted above are activated more powerfully through consistent movement than through any capsule.
Supplements are supportive tools. Exercise remains foundational.
Safety and Medical Guidance
Long-term human data for many longevity compounds are still evolving. These supplements should complement a disciplined foundation of nutrition, physical activity, sleep, and stress management.
Individuals taking prescription medications or managing chronic disease should consult a physician before beginning comprehensive supplementation, as some compounds may influence blood pressure, glucose levels, anticoagulation status, or liver enzymes.
Longevity is built through consistent lifestyle practices, supported when appropriate by evidence-informed supplementation.
— Dr. P
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