Paul is a wonderful host and really shaped a great conversation! Check it out here: 🧪

podcasts.apple.com/au/podcast/u...

In Part 1, we explore: 🧪

Why lysosomes are the forgotten organelle for longevity

How longevity interventions are discovered and what this means for their applications in humans.

How promising interventions SGLT2 inhibitors are already showing longevity promise in humans.

David is building a fascinating resource: a curated database of personal “longevity stacks” from scientists, physicians, and health optimizers with very diverse backgrounds. 🧪

Check it out at
wellstackedlife.com

I'm looking forward to joining David and John Gildea tomorrow to record a new episode of the Mara Labs podcast! Stay tuned.

Key sources 2: 🧪
📰 Lithium stabilizes cognitive impairment in AD:
pubmed.ncbi.nlm.nih.gov/22746245/
📰 Mechanistic insights in mice and observational data in humans:
www.nature.com/articles/s41...

Key sources 1: 🧪

📰 AD incidence with and without APOE4:
www.nature.com/articles/s41...
📰 Lithium in drinking water and AD prevalence:
jamanetwork.com/journals/jam...
pmc.ncbi.nlm.nih.gov/articles/PMC...

Discussed in detail in my latest Substack post. 🧪

jonbrudvig.substack.com/p/lithium-pr...

Observational and interventional studies tell us that microdoses in the range of 0.02–0.3 mg/day are protective. That’s thousands of times lower than psychiatric doses, with a nearly zero risk of toxicity or side effects, and very inexpensive.

This is easily achieved with lithium supplements. 🧪

So, why aren't we using it? Experts are hesitating to recommend lithium until optimal doses are confirmed in large, definitive trials.

But in high-stakes scenarios like this, waiting for confirmatory evidence could mean missing the window for prevention. Acting now is wise. 🧪

🧠 Mechanisms: blocks tau phosphorylation, shifts amyloid processing, clears plaques. 🧪

💊 Supplementing with 0.3 mg/day slows cognitive decline in Alzheimer's patients. 🧪

🫗 Natural lithium in drinking water → 20%+ reduction in Alzheimer’s rates. 🧪

This is supported by robust observational data from many thousands of individuals, small interventional studies in Alzheimer’s patients, and a relatively robust understanding of mechanism. 🧪

If you live to 95, your risk of developing dementia is 42%. For APOE4 carriers, it’s as high as 59%.

A trace mineral, lithium, can lower that risk at extremely low doses. So potently, that it could even counteract the impact of the worst genetic and environmental risk factors. 🧪

Huge disappointment is an understatement.

We have massive incentives to prioritize the health of ourselves and the planet over economic growth, but again and again we fail to do so. Devastating.

Key Sources 3: 🧪
📰 Metformin blunts exercise adaptations:
pmc.ncbi.nlm.nih.gov/articles/PMC...

📰 The case against metformin in healthy individuals:
drglorioso.substack.com/p/should-you...

Key Sources 2: 🧪

📰 Low dose metformin improves healthspan and lifespan in mice: pmc.ncbi.nlm.nih.gov/articles/PMC...

📰 Metformin decreases PD risk only when used at low doses: pmc.ncbi.nlm.nih.gov/articles/PMC...

📰 Metformin blunts exercise adaptations:
pubmed.ncbi.nlm.nih.gov/31557380/

Key Sources: 🧪
📰 Metformin MOA: www.nature.com/articles/s41...

📰 Metformin promotes metabolic health, prevents diabetes, and promotes modest, durable weight loss: pubmed.ncbi.nlm.nih.gov/11832527/

📰 Metformin reduces systemic inflammation: pubmed.ncbi.nlm.nih.gov/33412927/

We don’t yet have RCTs that can confirm the benefits in healthy individuals, and we likely won’t for quite some time. But with current evidence pointing towards benefits across many aging organs, one must also consider the risks of waiting for that evidence to exist.