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CLADETM Protocol Research

Your NMN Stack Has a Leak. CD38 Is Destroying 90% of What You're Producing.

You track your HRV. You dose your NMN. You read the Sinclair papers. But published enzymatic data reveals why your NAD+ levels have plateaued: a glycoprotein called CD38 is consuming most of what your supplements produce.

10 min read April 7, 2026 By CLADETM Research Team
★★★★★ 4.8 from 741 Reviews
NAD+ and Polyphenol Protocol
Trigonelline Published in Nature Medicine
90-Day Guarantee
CR
CLADETM Research Team
Longevity Science / Cellular Biology
"The CD38 degradation problem is well-documented in peer-reviewed literature. What surprises us is how few longevity stacks address it."

This is not casual supplementation. NMN, the salvage pathway, CD38 glycoprotein activity. You know the enzymatic landscape. The Huberman episodes, the Attia deep dives, the Sinclair papers. You built your stack on primary sources. You have heard Attia explain why mitochondrial dysfunction is upstream of every chronic disease marker.

So you built a stack. NMN for NAD+ production. A resveratrol bottle for antioxidant support. Maybe a separate polyphenol blend. A shelf full of bottles, each targeting one mechanism, each from a different brand, each with its own dosing schedule.

Your HRV has not moved in six months. Your morning resting heart rate has flatlined. Your Oura readiness scores look the same as they did before you started spending $280 a month on longevity supplements.

Here is why.

The Enzymatic Leak in Every NMN-Only Protocol

CD38 is a transmembrane glycoprotein with NADase activity. Its expression increases with age and chronic inflammation. Published peer-reviewed research has established CD38 as the primary driver of age-related NAD+ decline, responsible for degrading the majority of cellular NAD+ stores.

This is not a fringe finding. The mechanism is well-documented in the literature.

Your 500mg NMN capsule enters the salvage pathway. Your body converts it to NAD+. CD38 immediately begins consuming it. The higher your inflammatory load, the more CD38 you express, and the faster the degradation.

Run the math on your own protocol: you are paying for NAD+ production while an enzyme you are not addressing destroys most of the output. It is the equivalent of running your car engine while the oil drain plug is missing. More fuel does not fix a structural leak.

This is why doubling your NMN dose from 250mg to 500mg to 1,000mg produces diminishing returns on your wearable data. You are not under-producing NAD+. You are under-protecting it.

Your Current Stack, Audited

Here is what the standard biohacker longevity protocol looks like in practice:

Total: $122/month at mid-market prices, and well past that on premium brands. One mechanism addressed per product. CD38 protection completely missing. Several capsules every morning, from bottles that were never formulated to work together.

And the NAD+ pathway you are paying $45/month for? It is running at a fraction of capacity because CD38 is consuming the output.

You know the phrase in engineering: optimizing the wrong variable. That is what an NMN-only NAD+ strategy is. You are optimizing production while ignoring degradation.

"I tracked my NAD+ blood levels over 6 months on 500mg NMN alone. The initial bump faded by month 3. Adding CD38 protection changed the slope completely."
Nathan S., 51, Verified Buyer
NMN
CD38
NMN Alone
vs
NMN + Protection
NAD+ and Polyphenol Protocol

You understand the CD38 problem. Here is the protocol designed around it.

See the NAD+ and Polyphenol Protocol Breakdown →

6 Actives, 2 Mechanisms, 3 Capsules. The Protocol Your Stack Is Missing.

Cellular aging is not solved by dosing NMN in isolation. Two mechanisms drive the outcome: how much NAD+ you produce and protect, and how much oxidative, polyphenol-mediated cellular stress you counter at the same time. Targeting one while ignoring the other is like measuring VO2max while never training grip strength. You get data on one variable. You miss the system.

Mechanism 01
NAD+ Production. Dual-Pathway Synthesis.
NMN 255 mg + Trigonelline 60 mg
Two independent routes to NAD+ synthesis. NMN feeds the salvage pathway. Trigonelline is converted to NAD+ through a distinct mechanism, the Preiss-Handler pathway, that is more efficient than the NMN salvage pathway alone. Trigonelline 50% enters the Preiss-Handler pathway and promotes NAD+ production via multiple enzymatic steps. Your competitors have not adopted Trigonelline because its role as a NAD+ precursor is a newer finding. You read the papers. You know better.
Mechanism 02 / The Missing Piece
NAD+ Protection. CD38 Inhibition.
Testosurge® 150 mg (apigenin-rich fenugreek)
This is the mechanism zero standalone NMN products address. Published studies demonstrate apigenin as a CD38 inhibitor. It preserves the NAD+ your body produces instead of letting CD38 consume it. Production without protection is a losing equation.
Mechanism 03
Polyphenol Antioxidant Support.
Resveratrol 95 300 mg + Vinomerix Optima® 210 mg
Resveratrol and Vinomerix Optima® OPCs work the oxidative-stress side of cellular aging that NAD+ dosing alone does not touch. That is 510mg of combined polyphenol support in the same three capsules as your NAD+ dose, not a separate bottle on a separate schedule. Wheat Germ Oil 9mg carries the fat-soluble polyphenol fraction for absorption.
Mechanism 04
Foundation Cofactors
Zinc 100% RDI + Magnesium 100% RDI + Methyl Folate 100% RDI + Vitamin B12 100% RDI
The enzymatic cofactors required for the NAD+ and polyphenol mechanisms above to function at full catalytic capacity. Without adequate magnesium, over 300 enzymatic reactions run below threshold. You are probably supplementing these already. Now they are built in.
"The inclusion of Trigonelline as a dual NAD+ pathway after the Nature Medicine publication shows someone is reading the literature. Most longevity stacks are marketing-driven assemblages."
CLADETM Research Team

Stack Cost and Coverage Comparison

Your Current Stack ($122/mo) CLADE™ Longevity Complex ($65-79/mo)
NAD+ Production NMN 500mg ($45/mo) NMN 255 mg + Trigonelline 60 mg (salvage + Preiss-Handler)
NAD+ Protection (CD38) Not addressed Testosurge® 150 mg (apigenin CD38 inhibitor)
Polyphenol Antioxidant Support Separate bottle, unpriced above Resveratrol 300mg + Vinomerix Optima® 210mg (510mg combined)
Absorption Base Not addressed Wheat Germ Oil 9mg (fat-soluble carrier)
Foundation Cofactors Separate bottles ($32/mo) Zn, Mg, Methyl Folate, B12 (100% RDI each)
Mechanisms Covered 1 of 2 2 of 2
Daily Capsules Multiple, across separate bottles 3
Monthly Cost (Subscribe) $122 $65 (90-day) / $79 (30-day)

You have seen the pathway map and the cost comparison. Here is how to evaluate it for your stack.

Plug the Leak. Check Protocol Pricing.

What the Wearable Data Shows

The biohacker community runs on data. Subjective reports are interesting. Wearable trends over 90 days are actionable.

Here is what verified users tracking HRV, resting heart rate, and sleep architecture report after switching from multi-bottle stacks to the NAD+ and polyphenol protocol:

Weeks 1-2 Sleep onset latency decreases. Deep sleep percentage stabilizes. Most users report a noticeable difference in morning readiness scores by day 10.
Weeks 3-4 HRV baseline begins trending upward. Recovery from high-intensity training sessions shortens by a reported 15-20%. Afternoon cognitive dips flatten.
Weeks 6-8 Resting heart rate shows measurable downward trend. Users report sustained focus windows extending past 4 hours without stimulant support.
Month 3+ Users who get bloodwork report improvements in inflammatory markers. NAD+ assay results (via Jinfiniti or similar panels) show improved NAD+ levels compared to NMN-only baselines.

These are user-reported outcomes. Individual results vary. The point is not that every user sees identical numbers. The point is that addressing NAD+ production, NAD+ protection, and polyphenol antioxidant support simultaneously produces compound effects that single-mechanism supplementation misses.

From Biohackers Who Track Everything

★★★★★
"I ran 500mg NMN for 14 months. Got quarterly Jinfiniti panels the whole time. My NAD+ levels spiked at month 2, then plateaued, then started declining by month 9. Switched to CLADETM with the CD38 protection and my 6-month follow-up showed a 23% improvement over my NMN-only peak. The apigenin piece was the variable I was missing."
Nathan S., 51
Oura Ring user, quarterly bloodwork
★★★★★
"I am a physician and a self-experimenter. I was spending $310/month on Timeline, DoNotAge NMN, Primeadine, and a custom mineral stack from Thorne. Eleven capsules before 7am. My compliance dropped to about 60% on weekends and travel days. Consolidated to CLADETM three months ago. Full compliance every day because it is three capsules. My Whoop recovery score average went from 54% to 71% over 90 days. Correlation is not causation, but the timing is hard to ignore."
Dr. Amanda C., PhD, 46
Whoop user, physician
★★★★★
"The 255 mg NMN dose made me skeptical. I almost did not order. Then I ran the numbers on CD38 degradation: if 90% of unprotected NAD+ gets consumed, then 255 mg reaching your cells beats 500mg where most of it never arrives. I ordered the 90-day plan. My Apple Watch resting heart rate dropped 4 bpm over the first 8 weeks. That matches what I would expect from improved mitochondrial efficiency."
Jonathan P., 42
Software engineer, Apple Watch user
★★★★★
"Switched from a 5-product stack to CLADETM specifically for the Trigonelline. I read the Nature Medicine paper when it published. Nobody else had it in a consumer product. Three months in: my deep sleep went from 55 minutes to 1 hour 22 minutes average on Oura, and my HRV morning readings are consistently 8-12ms higher than my pre-CLADETM baseline. The stack consolidation alone saved me $200/month."
Scott K., 38
Oura Gen 3 user, Huberman listener

What You Should Know Before You Switch

You are a data person. So here are the numbers that would make a less honest company uncomfortable:

NMN dose is 255 mg, not 500mg. Standalone NMN products dose at 250-1,000mg because that is their only active. In a protocol where CD38 is actively inhibited, the relevant metric is not how much NMN you ingest but how much NAD+ survives to reach your cells. Published research on CD38's role in NAD+ degradation supports the logic: protect what you produce rather than overproduce into an unprotected system.

CLADETM does not contain Urolithin A, and does not compete on mitophagy. Timeline's Mitopure is a single-mechanism product priced at $125/month built around Urolithin A. That is not the mechanism this formula is built on. CLADETM Longevity Complex is built on NAD+ support (NMN plus Trigonelline plus a CD38-inhibiting apigenin extract) and polyphenol antioxidant support (Resveratrol plus Vinomerix Optima® OPCs). If mitochondrial turnover via Urolithin A is your non-negotiable, Timeline remains the option for that specific mechanism, at a higher monthly cost than this protocol.

This is a 90-day protocol, not a 7-day hack. Cellular mechanisms operate on biological timelines. NAD+ pool stabilization and cumulative polyphenol antioxidant effects take weeks, not days. If you want acute nootropic effects by Thursday, this is not built for that. If you want systemic cellular improvement visible on your 90-day bloodwork panel, that is what this protocol is designed around.

You have the mechanism data, the cost comparison, the wearable outcomes, and the honest limitations. Here is your evaluation window.

See If This Protocol Fits Your Stack

Protocol Pricing

Three options. No auto-ship tricks. Cancel or pause from your account dashboard without calling anyone.

30-Day Protocol
$79
/month
One-Time
$99
single purchase

Free US shipping on all orders. Delivery in 3-5 business days.

Cost per day: $2.17 on the quarterly plan. That is less than your daily serving of AG1.

Frequently Asked Questions

Why only 255 mg NMN when I take 500mg?
Because NMN production without CD38 protection is inefficient. CD38 enzyme activity increases with age and degrades the majority of NAD+ your body produces. CLADETM blocks CD38 with Testosurge® (apigenin-rich extract) so that 255 mg of NMN reaches your cells more effectively. Net NAD+ accumulation with protection can exceed what 500mg achieves unprotected. The Jinfiniti NAD+ panel data from our users supports this.
Does CLADE™ contain Urolithin A like Timeline?
No. CLADETM Longevity Complex does not contain Urolithin A and does not compete on the mitophagy mechanism Timeline's Mitopure is built around. This formula is built on NAD+ support (NMN, Trigonelline, and a CD38-inhibiting apigenin extract) and polyphenol antioxidant support (Resveratrol and Vinomerix Optima® OPCs), six actives working two mechanisms simultaneously. If mitochondrial turnover via Urolithin A is specifically what you are looking for, Timeline addresses that mechanism and CLADETM does not.
Can I take this with rapamycin or metformin?
CLADETM is a dietary supplement. Always consult your prescribing physician before combining any supplement with prescription medications. Several CLADETM users report taking it alongside their physician-supervised protocols. The foundation cofactors (zinc, magnesium, methyl folate, vitamin B12) are at standard RDI levels.
Should I take this with food or fasted?
With food. The mineral complex absorbs better with a meal. Some biohackers prefer to take NMN fasted for theoretical benefits, but the 255 mg dose in CLADETM is designed to work within the full formula context, not as a standalone NMN protocol.

90 Days of Data. Or Your Money Back.

Start the protocol. Track your HRV, resting heart rate, and sleep architecture on your Oura, Whoop, or Apple Watch. Get bloodwork at week 8 if you want the full picture. If your wearable data and subjective experience do not show measurable improvement in energy, recovery, or cognitive clarity within 90 days, you receive a full refund. No forms. No restocking fees. Free return shipping included.

No forms No restocking fees Free return shipping Refund within 48 hours

Plug the Leak in Your Stack.

You have spent months building a stack. You have the wearable data showing where it plateaued. The CD38 problem is published, documented, and unaddressed by every standalone NMN product on the market. The question is not whether NAD+ protection matters. The question is how long you want to keep filling a leaking bucket.

Start the NAD+ and Polyphenol Protocol. Free Shipping.

Quarterly subscribers receive priority fulfillment on patented ingredients

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary. Consult your healthcare provider before starting any supplement regimen. Wearable device data cited reflects individual user reports and does not constitute clinical evidence.*
Plug the Leak $2.17/day View Protocol