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Mike Lustgarten's Self-Experiment: NAD+ and Homocysteine Supplementation

S-adenosyl-methionine: A Key Player For Lowering Homocysteine?

TL;DR

Longevity self-experimenter Mike Lustgarten documents his supplementation protocol targeting NAD+ levels and homocysteine reduction, measuring outcomes via biological age calculators and blood biomarkers. While he achieved a 48 µM NAD+ level (considered 'optimal' by his lab) and 9.3 µM homocysteine, he candidly notes his biological age result was his worst across seven tests, questioning whether the interventions actually improved his metrics.

Why This Matters

Longevity self-experimenter Mike Lustgarten documents his supplementation protocol targeting NAD+ levels and homocysteine reduction, measuring outcomes via biological age calculators and blood biomarkers.

Credibility Assessment Disputed — 24/100
Study Design
Rigor of the research methodology
3/20
Sample Size
Whether the study was sufficiently powered
2/20
Peer Review
Review status and journal reputation
5/20
Replication
Has this finding been independently reproduced?
2/20
Transparency
Funding disclosure and data availability
12/20
Overall
Sum of all five dimensions
24/100

What this means

This is a well-documented personal experiment showing one person's biomarker changes from supplementation, characterized by admirable honesty about disappointing results—but it provides no evidence that this supplement protocol actually slows aging or extends lifespan. The candid finding that intensive supplementation coincided with his worst biological age score suggests caution before adopting similar strategies without medical oversight.

Red Flags: YouTube video — not peer-reviewed research. **No citations for core claims**: Homocysteine's neurotoxic mechanisms, SAM's role in homocysteine metabolism, and the 5 µM homocysteine 'optimal' target are asserted without references. **Conflicting results not adequately explained**: The video's core tension—that intensive supplementation yielded the worst biological age result—is acknowledged but not resolved. Viewers could conclude either (a) supplements don't work, or (b) the biological age calculator is uninformative, but Lustgarten doesn't explore this. **Single n=1 with uncontrolled variables**: No control for diet, sleep, stress, or supplement interactions during the 41-day window. **Credentialing mismatch**: Lustgarten is a data analyst, not a gerontologist or physician; his credibility relies on careful self-measurement rather than research training. **Patreon monetization**: The video promotes a paid tier claiming biomarker optimization data (52 references), but this content is not transparently accessible for fact-checking. **Rapid NAD+ fluctuations acknowledged but not fully addressed**: He notes NAD+ changes in 2-3 days, yet bases conclusions on 17-day and 4-day supplementation windows with dosing that varied within those periods. **No safety discussion**: Long-term effects of NMN/nicotinamide or the supplement stack are not addressed.

Mike Lustgarten presents a detailed self-experiment combining NAD+ precursors (nicotinic acid, nicotinamide, and NMN) with homocysteine-lowering supplements (riboflavin, betaine/TMG, and zinc) over a 41-day period, culminating in blood testing. He measures outcomes using Dr. Morgan Lavine's Pheno Age calculator (a blood-based biological age estimator using nine clinical chemistry biomarkers) and direct NAD+ quantification via Zymo Research. His NAD+ increased from 21 µM (previous test with nicotinamide alone) to 48 µM with NMN supplementation, which he attributes partly to the monucleotide addition to nicotinamide. His homocysteine measured 9.3 µM, below the clinical high-threshold of 15 µM, though he targets 5 µM based on published literature correlating homocysteine with aging and mortality risk.

Lustgarten demonstrates notable intellectual honesty by acknowledging a critical limitation: despite achieving favorable individual biomarker results, his biological age showed a 15-year advantage—his worst result across seven tests. He explicitly questions whether his multi-supplement protocol improved biomarker data or potentially worsened it, explicitly stating "one could make the argument that all of these supplements didn't do anything." This candor is rare in longevity content. He also discloses methodological details (custom stock solutions, dose averaging over 41 days, headaches prompting dose reductions) and notes that NAD+ levels change rapidly with supplementation changes, potentially confounding interpretation.

However, significant evidentiary gaps exist. The video cites no peer-reviewed studies establishing that S-adenosylmethionine (SAM) or the specific supplement stack reduces homocysteine or improves aging outcomes in humans. While homocysteine's neurotoxicity and association with endothelial senescence are mentioned, no citations are provided. His 'optimal' homocysteine target (5 µM) and NAD+ interpretation (citing metabolomic correlations) lack published references in this segment. The Pheno Age calculator itself is peer-reviewed, but whether a 15-year biological age advantage (even as his worst result) translates to longevity or health gains remains unestablished. His new Patreon tier claiming optimized biomarker targets across 35 markers references 52 published papers, but viewers cannot assess their quality or applicability without access.

The experiment is fundamentally a single n=1 case study without control conditions, blinding, or randomization. Lustgarten is not a credentialed aging researcher (his background is in finance/data analysis based on public information), though he demonstrates strong scientific literacy and careful self-measurement. The video conflates correlation (metabolomic associations with NAD+) with causation and lacks clarity on whether supplement timing, interactions, or external confounders (diet, stress, sleep during the 41-day period) influenced results.

Viewers should understand this as detailed biohacking documentation rather than evidence that this supplement protocol extends lifespan or improves aging. The candid acknowledgment that his 'worst' biological age result accompanied his most intensive supplementation is the video's most valuable contribution—it challenges the assumption that more interventions equal better outcomes.

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