Parkinson’s is often framed as a brain-first disorder, but some of its earliest changes unfold in the gut. This episode unpacks a global metagenomic analysis showing that two surprisingly ordinary microbial compounds, ones most people consume every day, quietly disappear in Parkinson’s. When these pathways vanish, gut defenses weaken, protective metabolites fall, and enteric neurons may become vulnerable to the toxins that start pathology long before tremors appear.

The goal: reveal how the loss of these two everyday compounds reshapes gut biology in ways that could precede neurodegeneration, and clarify why restoring their microbial pathways may be far more important than previously recognized.

00:00 A Different Origin Story for Parkinson’s
00:33 Early Clues That Don’t Start in the Brain
01:15 A Possible Route From Gut to Brain
02:10 The Missing Pathways No One Expected
02:59 What a Six-Country Analysis Revealed
05:07 How These Lost Functions Reshape Gut Biology
08:33 What This Means for Prevention and Intervention
10:53 Closing the Loop: Why the Gut Matters

PMID: 37314861

A new brain-imaging meta-analysis has uncovered the first consistent biochemical signature across multiple anxiety disorders (a shift in a single molecule that moves in the opposite direction of every major psychiatric condition studied to date). Even more surprising, a separate study in young adults under metabolic strain reveals a nearly identical pattern emerging outside the brain. In this episode, we trace the science behind this unexpected overlap, follow the trail of this overworked molecule, and explore what these clues suggest about the hidden biology anxiety leaves behind.

00:00 A New Chemical Clue in Anxiety Disorders
00:33 How Common Anxiety Really Is — and Why It’s Hard to Treat
01:24 A Biochemical Pattern That Reverses Every Expectation
02:52 The Molecule Behind the Cortical Signal
04:26 What Chronic Stress Does to This Molecular Pathway
08:13 How to Support the Brain Systems This Molecule Serves
09:20 Final Thoughts: Caring for the Biology Behind Anxiety

PMID: 40913113

PMID: 26886842

PMID: 19656836

PMID: 41296930

Magnesium salts are often marketed as if they target specific tissues - i.e., “threonate for the brain,” “glycinate for calm,” “taurate for the heart.” Part 2 breaks down what the evidence actually shows: animal studies demonstrating tissue differences that have never been replicated in humans, cognitive and sleep trials where multiple forms show benefit, and meta-analytic data indicating what really drives long-term outcomes.

The goal: clarify the real distinctions between magnesium forms, ligand effects, and dose requirements so listeners can understand what truly determines magnesium’s impact in humans.

00:00 Introduction to Magnesium Forms

00:22 Zooming Out: Broader Human Data

01:08 Systematic Reviews and Meta-Analyses

02:10 Key Findings on Magnesium Benefits

04:05 Understanding Magnesium Salts and Ligands

07:13 Practical Applications and Recommendations

09:32 Conclusion and Final Thoughts

• Doi: 10.1186/s40795-016-0121-3
• PMID: 11550076
• PMID: 31330811
• PMID: 39252819
• PMID: 26519439
• PMID: 34111673
• PMID: 23853635
• doi: 10.3390/nu9050429
• PMID: 39009081

Magnesium supplements are marketed like different compounds with different biological targets - i.e., “for sleep,” “for the brain,” “for stress,” “for energy.” But the foundation of these claims depends on chemistry: how magnesium salts dissolve, how they release Mg²⁺ in the gut, and how much actually reaches circulation.

Part 1 breaks down the first half of the magnesium story: why magnesium must be paired with a counter-ion, how dissolution determines real absorption, and what modern data show when common salts like citrate, glycinate, and oxide are compared head-to-head.

The goal: separating marketing myths from measurable differences in solubility, acute bioavailability, and baseline magnesium status

00:00 Introduction to Magnesium Forms

00:30 Magnesium's Chemical Nature

01:11 Absorption Differences Among Magnesium Forms

01:35 Clinical Studies on Magnesium Absorption

04:24 Magnesium in Animal Studies

06:05 Human Studies on Magnesium

08:47 Conclusion and Preview of Part Two

• Doi: 10.1186/s40795-016-0121-3
• PMID: 11550076
• PMID: 31330811
• PMID: 39252819
• PMID: 26519439
• PMID: 34111673
• PMID: 23853635
• doi: 10.3390/nu9050429
• PMID: 39009081

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/

Every few days, your gut rebuilds itself completely - cell by cell, guided by signals we still don’t fully understand. For years, scientists have known that diet can influence this process, but the exact messenger between what we eat and how the gut heals has remained a mystery.

In this episode, we look at new research from MIT that uncovers a surprising link between diet, the immune system, and regeneration in the intestine. It’s a story about how a single nutrient can activate immune cells to release molecules that tell the gut when it’s time to repair.

It challenges the way we think about food, not just as fuel, but as information. Because the gut isn’t just digesting what we eat… it’s listening.

00:00 Introduction to Gut Regeneration

00:56 The Role of Amino Acids in Gut Health

02:07 ???: A Key Player in Gut Regeneration

02:35 MIT's Groundbreaking Research

03:49 The Immune System's Role in Gut Regeneration

05:51 Dietary Sources and Implications

07:07 Conclusion: The Gut's Adaptive Nature

PMID: 41034585