A medication used by millions (including off-label usage for “longevity” purposes) may alter the fundamental pathways responsible for exercise adaptation. This episode reviews new 2025 data showing reduced improvements in vascular insulin sensitivity, aerobic capacity, and glucose regulation when the medication is paired with structured training. We look at prior evidence of blunted mitochondrial respiration and diminished hypertrophy, along with 2020 transcriptomic findings that paint a more nuanced picture.

The goal: clarify when this medication interferes with exercise-driven improvements in muscle, mitochondria, and vascular function, and when it may support resilience during aging.

00:00 – Intro
00:48 – The Rise of a “Longevity” Medication
01:31 – New Clinical Data Challenges Expectations
03:34 – Earlier Trials Showed the Same Pattern
05:05 – Resolving the Apparent Contradiction
07:10 – Who Should, and Shouldn’t, Use This Medication

PMID: 30548390
PMID: 31557380
PMID: 33071237
PMID: 37928155

There’s a molecule that’s been tentatively identified in the same interstellar material that forms stars and planets, yet it also shapes growth, metabolism, and cognition here on Earth. In several mammalian species,Its absence causes deficiency and it's repletion, resolution; and no, it’s not a vitamin, but should it be?

Its chemistry is analogous to the combination of vitamin B2, vitamin B6 vitamin C, and its role in evolution may trace back to the very beginning of biology.

00:00 – From Interstellar Dust to Human Biology
01:06 – Discovery: A New Redox Co-Factor
01:44 – Biological Role: Deficiency, Growth, and Evolution
02:41 – Mechanisms: NAD⁺ Regeneration and Mitochondrial Signaling
03:11 – Human Evidence: Cognitive and Metabolic Effects
04:41 – Chemistry & Safety: Potency and Tolerability
06:55 – Conclusion

https://pmc.ncbi.nlm.nih.gov/articles/PMC8533503/

Serotonin is often described as the “happiness molecule,” but its biology tells a larger story. Nearly every step in serotonin’s synthesis and signaling, from the transport of dietary tryptophan to the enzymes that convert it, is influenced by nutrition.

This episode examines how macronutrients, micronutrients, and gut-derived metabolites shape serotonin availability across the brain and body. Protein and carbohydrate balance determine how much tryptophan enters the brain. Specific vitamins and minerals serve as essential cofactors in its production and turnover, and so on…

Understanding serotonin through this nutritional lens reframes it not as a simple neurotransmitter, but as a metabolic signal connecting diet, metabolism, and mood regulation.

00:00 Introduction to Serotonin

01:07 Evolutionary Role of Serotonin

02:08 Nutritional Influence on Serotonin Synthesis

02:55 Enzymatic Pathways of Serotonin Production

04:21 Macronutrients: Impact on Serotonin

06:32 Vitamins and Minerals: Impact on Serotonin

09:27 Plant Compounds and Gut Microbiome: Impact on Serotonin

10:24 Serotonin as a Biochemical Bridge

https://pubmed.ncbi.nlm.nih.gov/40998119/