Hey there, it’s Nick Engerer, strategic advisor at DoNotAge and someone who’s spent the last decade treating my own body like a personal longevity laboratory. If you’ve followed my earlier posts (the multi-part series on Calcium Alpha-Ketoglutarate, Ca-AKG) then you know I’m a big believer in stacking interventions that target aging from complementary angles rather than chasing single “magic bullets.”

After I shared my post about top questions related to Ca-AKG late last year, I became aware of another question that the DoNotAge team were constantly receiving from readers: “I am already using DoNotAge’s NMN, but I don’t know what to add next. There are too many choices.”

Perhaps it’s no surprise, but in my personal opinion the answer just might be Ca-AKG. This is because from a first-principles biological view these two ingredients work together for cellular energy production in a way that feels almost engineered for synergy and overall resilience.

Let’s break down why NMN + Ca-AKG makes such a compelling pairing, grounded in the biology and the emerging evidence.

The Engine Analogy: Fuel Meets Tune-Up

Most of the DoNotAge audience is already convinced by the NMN-as-cellular-fuel logic. Your cellular energy systems run on NAD+, levels fall with age, and replenishing them supports more youthful function. Since this supplement hit the scene about six years ago, human science has backed it up. Start taking NMN, boost NAD+—many of you report steadier energy, better recovery, sharper focus.

But to understand why Ca-AKG might be next, extend the thinking. Picture your mitochondria (the power plants inside every cell) as tiny engines. As we age, they clog with metabolic “gunk”: declining Krebs cycle intermediates, inefficient electron flow, rising reactive oxygen species (ROS), and NAD+ shortages hobbling repair.

NMN is like pouring in premium, high-octane fuel: it boosts NAD+, powering sirtuins for DNA repair, inflammation control, mitochondrial biogenesis, and epigenetic reset.

But even with great fuel, a clogged engine can’t run at peak efficiency. That’s where Ca-AKG steps in as the oil change and tune-up. Alpha-ketoglutarate (AKG) is a central Krebs cycle intermediate, converting food to ATP. Natural levels plummet—down to around 10% by our 80s compared to our 40s—creating bottlenecks, excess ROS, and a shift to catabolism over anabolism. The calcium-bound form improves stability and absorption, restoring cycle pools, smoothing electron transport, reducing ROS, activating AMPK while dialing back mTOR.

Alone, each shines. Together, cleaner pipes plus better fuel equals a leaner, cooler, longer-running engine. AMPK goes up, mTOR is balanced, autophagy is encouraged—mimicking calorie restriction or exercise benefits without the effort.

The Science Behind the Pairing

While definitive human combination outcomes are still emerging, cellular and animal evidence supports the logic.

1) The Krebs cycle feeds reduced NADH to the electron transport chain for ATP, but NAD+ is key for handover. Low AKG creates bottlenecks that waste even abundant NAD+.

2) Ca-AKG helps unclog this, stabilizing NAD+/NADH ratios, bolstering glutathione (the master antioxidant), and favoring repair.

3) NMN supplies fresh NAD+ to leverage that cleaner machinery, amplifying sirtuins, mitochondrial renewal, and DNA protection.

Preclinical hints are promising. Ca-AKG alone extends lifespan by roughly 10–12% in models, reduces frailty, boosts ATP, and lowers inflammation via mTOR and AMPK pathways. Human pilot studies (like the one I covered earlier) show improvements in biological age markers and grip strength.

A 2025 Journal of Aging Science study really switched me onto combinations. Researchers tested mixes in C. elegans (worms), including a “Formula 1” heavy on NMN and AKG (plus quercetin, spermidine, and others). It outperformed controls, including resveratrol, on lifespan and healthspan, showing better late-life mobility and survival via sirtuin modulation, senolytics, and immune rejuvenation. It wasn’t a pure NMN plus Ca-AKG stack, but it strongly supports additive effects across aging hallmarks.

I expect human research to shift toward multi-ingredient formulations over the next five years. The mechanistic overlap is strong: optimized mitochondria, reduced oxidative stress, broader biological coverage. Many enthusiasts already stack intuitively, and my own tracking, along with anecdotal feedback, shows steadier energy, faster recovery, and improved resilience.

How to Stack These Ingredients

From trials, NMN is commonly taken at 500 mg to 1 g daily. Ca-AKG typically runs at 1 to 2 g per day, for example 1 g once daily or split doses.

If you’re already on DoNotAge NMN and wondering what to self-experiment with next, Pure Ca-AKG is a logical and relatively low-risk addition. Start with 2 to 3 capsules (around 800 to 1200 mg) daily and track your response over 4 to 12 weeks. Always consult your doctor, especially if you have kidney concerns or are taking medications.

For a limited time in (February 2026), you can save 27% on the combined price with “The Energy Bundle.”

The longevity future is accelerating. Smart stacking helps keep us ahead and healthy enough today to benefit from tomorrow’s breakthroughs.

Here’s to thriving longer and stronger,
Nick Engerer

Strategic Advisor, DoNotAge