Just to be of service (as well as avoiding the 15 mins of watching this)
Tidied transcript
NAD is required for mitochondrial energy production, and that's what we'll see here, starting off in the mitochondrial matrix—more specifically in the TCA cycle. NAD is required for flux through the TCA cycle as a co-factor for the conversion of isocitrate into α-ketoglutarate (AKG) and for the conversion of AKG into succinyl-CoA. As a by-product of those two reactions, two moles of NADH are produced. NADH donates its protons to Complex I, which then pumps them out; its electrons move through the electron-transport chain, culminating in ATP production.
NAD may decline during ageing (some studies show the decline, others do not). If NAD is low, less NADH is produced and mitochondrial ATP production—at least through Complex I—falls. So, if we raise NAD, will mitochondrial function improve? To test that, we can track NAD levels. I’ve tested mine 26 times using Genfinity’s assay (discount link in the description).
But what about plasma biomarkers of mitochondrial function? Lysophosphatidylcholines (LPCs) have been associated with mitochondrial oxidative capacity. Because this is the first time I’ve introduced LPCs on the channel, let’s define them. Take phosphatidylcholine 18:0/20:4, which contains stearic acid (18:0) and arachidonic acid (20:4) esterified to a glycerol backbone, itself linked to phosphocholine (PC). Under pro-inflammatory conditions, phospholipase A2 cleaves off one fatty acid, releasing arachidonic acid and leaving lysophosphatidylcholine 18:0.
In a published study, plasma LPC levels (from 16:0 up to 20:3 species) were compared with in-vivo skeletal-muscle mitochondrial function measured by ^31P-MRS of post-exercise phosphocreatine recovery. Quartile 1 had the worst mitochondrial function and the lowest LPCs; quartile 4 had the best and the highest LPCs. All LPC species except 16:0 were significantly associated with mitochondrial function. VO₂max followed the same trend (19 mL·kg⁻¹·min⁻¹ in Q1 vs 26 in Q4). When the authors grouped Q4 versus Q1-3, all seven LPC species, including 16:0, were significantly higher in Q4.
I track LPCs at home with I-Omics’ metabolomics kit (link in the description). That lets me ask whether blood NAD is associated with LPC biomarkers of mitochondrial function. Plotting my intracellular NAD (Genfinity) against the sum of those seven LPCs (I-Omics), the overall correlation is non-significant. One point may be an outlier: mathematically, it lies >3 SD above the mean (∼325 µM vs a 172 µM cut-off). Yet huge LPC elevations (≥3-fold) have been reported in people who later develop Alzheimer’s disease, so perhaps it is an early-warning signal rather than an outlier.
Removing that point, NAD and LPCs are now significantly *inversely* correlated (r = -0.59, p = 0.04)—opposite to the expectation that higher NAD means better mitochondrial function. On days when I boost NAD with precursors (nicotinic acid or NMN) to 50–60 µM, LPCs look *worse*—again opposite to expectations. Over the remaining 10 tests (NAD 19-32 µM) there’s no correlation.
Three possibilities emerge:
1. **High** NAD correlates with **low** LPCs—suggesting worse mitochondrial function.
2. **Intermediate** NAD (~30 µM) with mid-range LPCs may be optimal.
3. **Very high** LPCs with low NAD could flag Alzheimer’s risk.
If you wonder what’s optimal for biomarkers, I’ve created a new Patreon tier covering 29 markers, their age-trajectories and mortality links (45 references, >2 hours of content). I also post daily updates in several Patreon tiers. Finally, discount and affiliate links below: UltaLabTests, Clearly Filtered, at-home metabolomics, oral-microbiome kits, NAD testing, epigenetic clocks, CyOx Health, Cronometer, merch, and Buy-Me-A-Coffee. Thanks for watching—Conquer Ageing or Die Trying!
Summary
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Biochemical context: The speaker explains how NAD⁺/NADH drives mitochondrial ATP production through the TCA cycle and Complex I.
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Ageing premise: He notes that some—but not all—studies show NAD⁺ declines with age, potentially impairing mitochondrial output.
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Biomarker focus: Plasma lysophosphatidylcholines (LPCs) are introduced as putative, non-invasive markers of skeletal-muscle mitochondrial oxidative capacity, citing a study in 73-year-olds in which higher LPCs tracked with better in-vivo mitochondrial function and higher VO₂max. (Johns Hopkins University)
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Self-experiment: The narrator has measured his own intracellular NAD 26 times (Genfinity) and LPCs 13 times (I-Omics). When plotted together, the relationship is muddied by one very high-LPC datapoint.
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Outlier or signal?: He notes that similarly large LPC surges have preceded Alzheimer’s disease in a longitudinal cohort and wonders if his ‘outlier’ might be a warning. (PMC)
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Paradoxical finding: After removing the point, higher NAD correlates negatively with mitochondrial-function LPCs (r ≈ -0.6). Days with NAD boosters (nicotinic acid/NMN) show higher NAD but lower LPCs—contrary to the hypothesis that more NAD improves mitochondria.
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Speculation: He proposes (i) too much NAD may be counter-productive, (ii) ~30 µM NAD might be optimal, or (iii) very high LPCs with low NAD could predict neurodegeneration.
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Commercial angle: The video ends with promotions: Patreon tiers for “optimal biomarker” ranges and discount links to multiple testing kits and merchandise.
Critique
| Aspect |
Observations |
| Evidence base |
The mitochondrial-function study he cites is cross-sectional (Baltimore Longitudinal Study of Ageing) with older adults; LPCs correlated with kPCr but causality is unproven. (Johns Hopkins University) |
| NAD-age narrative |
He fairly notes that NAD⁺ decline with age is inconsistent. Recent reviews echo this: human data are sparse and often tissue-specific. (PMC) |
| n = 1 design |
All correlations come from a single individual (the presenter). Biological noise, assay variance, diet, exercise and circadian factors are uncontrolled; statistical inference is therefore meaningless. |
| Outlier handling |
Treating the extreme LPC value as both an “outlier” and a possible Alzheimer’s warning is internally contradictory. Linking one data point to dementia risk ignores that the AD study compared group means over hundreds of participants and used a phosphatidylcholine/LPC ratio, not absolute LPC sums. (PMC) |
| Reverse inference |
The inverse NAD–LPC relationship may reflect assay artefacts (whole-blood NAD vs plasma LPC), different tissue pools, or confounding (e.g., fasting status). Declaring that “high NAD hurts mitochondria” overshoots the data and conflicts with many cell-culture and animal studies showing NAD repletion improves bioenergetics. |
| Measurement validity |
The Genfinity whole-blood NAD assay is still proprietary and lacks peer-reviewed validation. LPC quantification from a mail-in dried-blood-spot kit likewise has uncertain accuracy. |
| Conflict of interest |
The video promotes discount links to the very assays under discussion and markets paid Patreon tiers. Viewers should weigh the commercial incentive when interpreting the conclusions. |
| Missing controls |
No replicate samples, blinded repeats or external labs are used. Lifestyle factors (training load, infection, supplement wash-out) are not reported, yet each can shift both NAD and LPCs. |
| Alternative explanations |
LPCs rise in acute inflammation and can be neuro-toxic; higher values are not necessarily “better” for mitochondria. Some studies even link elevated LPCs to metabolic and neuro-degenerative pathology. (PMC) |
Bottom line:
The biochemistry primer is clear and the idea of pairing NAD⁺ measurements with lipidomics is intriguing. Nevertheless, the video’s central claim—that personal data reveal an optimal mid-range NAD⁺ and that boosting NAD may impair mitochondria—is unsupported outside an anecdotal, commercially entangled n = 1 dataset. Larger, controlled studies using validated assays are needed before treating LPCs as actionable mitochondrial biomarkers or redefining NAD-boosting strategies.
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