New Research Suggests That Unique Compound Found in Mushrooms Could Protect Your Brain From Alzheimer’s By Boosting NAD+

A curious chain of discoveries has me thinking about a certain mushroom-derived molecule in whole new light 

It started with a December study that made waves in Alzheimer’s research. A team publishing in Cell Reports Medicine found that the brain’s inability to maintain normal levels of NAD+ (a molecule critical for cellular energy) appears to be a major driver of Alzheimer’s disease. More importantly, they demonstrated that restoring NAD+ balance could prevent and even reverse the disease in mouse models.

Although it’s in mice and not humans, this is still big news. The lead author and team used multiple preclinical approaches alongside analysis of human Alzheimer’s brains to build their case.

Here’s when something clicked for me. I remembered seeing recent research suggesting that ergothioneine – a compound found abundantly in mushrooms – increases NAD+ levels in animals and is also associated with cognitive on population scales. Intrigued, I dug deeper.

Following the Trail

The ergothioneine-NAD+ link comes from a February study in Cell Metabolism. The researchers investigated how ergothioneine affects healthspan in ageing animals, finding lifespan extension and improved mobility in C. elegans worms, along with better exercise endurance and muscle mass in aged rats. They showed that ergothioneine acts as an alternative substrate for an enzyme called cystathionine gamma-lyase, which produces hydrogen sulfide, ultimately activating a protein that boosts NAD+ levels in muscle tissue.

The study documented protein modifications in over 300 targets – a cascade of cellular effects all stemming from this mushroom-derived molecule.

But animal studies are just the beginning of the story. A comprehensive review published by Cambridge University Press in September surveyed the human evidence, and it’s surprisingly consistent. Observational data repeatedly links low blood ergothioneine levels with cognitive impairment, neurodegenerative diseases, cardiovascular disorders, frailty, and mortality.

The review’s authors noted that ergothioneine works through multiple pathways: reducing oxidative stress, tamping down neuroinflammation, preserving mitochondrial function, and potentially modulating neurogenesis alongside that NAD+ metabolism connection. They concluded that current evidence positions ergothioneine as “a promising nutritional intervention for promoting cognitive resilience and systemic health in ageing,” though they appropriately call for larger, longer trials.

The Human Data

Speaking of human trials, a June study published in Foods tested ergothioneine supplementation in healthy older adults with subjective memory complaints. The randomised, placebo-controlled trial found improvements in prospective memory (remembering to do things in the future) and sleep initiation at a 25mg dose, with benefits emerging in a dose-dependent manner.

“Ergothioneine supplementation was safe and well tolerated, with evidence suggesting some benefits in this cohort of healthy older adults,” the authors wrote. They also noted improvements in liver function and, intriguingly, a within-group increase in telomere length, though that finding needs replication.

The effect sizes weren’t enormous, but they were statistically significant and, importantly, occurred in people who were already cognitively healthy. This suggests potential for prevention rather than just treatment.

Beyond Biomarkers

What strikes me most about the September review is its discussion of ergothioneine as a dietary biomarker of healthy ageing. Populations eating more ergothioneine-rich foods (primarily mushrooms, but also oats) show slower cognitive decline and greater metabolic resilience. This relationship persists even after controlling for overall diet quality and lifestyle factors.

That statistical persistence matters. It suggests ergothioneine isn’t just a marker of people who eat well and live healthily. It may be actively contributing to those outcomes.

The Bigger Picture

We’re witnessing a shift in longevity science from treating disease to preventing decline. Ergothioneine sits right in that sweet spot as a compound that’s gentle in mechanism yet potentially profound in its long-term effects. It addresses oxidative stress and inflammation, two processes that underlie both normal ageing and diseases like Alzheimer’s.

The pathway from ergothioneine through hydrogen sulfide signaling to NAD+ maintenance to cellular energy to cognitive preservation represents exactly the kind of multi-level intervention that biological systems respond to. Rather than targeting one thing, it’s a nudge toward better equilibrium across multiple systems.

If larger trials confirm what these early studies suggest, ergothioneine might transition from curiosity to a cornerstone of preventive care. The doses studied (up to 25mg daily) appear safe with no concerning side effects, and the compound is abundant in common culinary mushrooms like shiitake, oyster, and especially porcini.

Nature, and particularly mushrooms, continue to astound me. They show that the future of health might not require exotic, patented pharmaceuticals or cutting-edge gene therapies. It might grow in the soil beneath our feet, in the mycelium networks that have been here far longer than we have, waiting for us to notice the elegant solutions they’ve been offering all along.