Protocols — Supplement Stacks by Goal

A protocol is a small group of supplements that work better together than alone. Below are six protocols organized by goal, each with a recommended starting stack, a daily dosing schedule, and the science behind why these specific compounds belong in the same routine. Pick the protocol that matches what you want to feel — energy, smoother skin, sharper metabolism, fewer years on the inside — and run it for at least 8–12 weeks before judging results.

Every protocol uses products already in our catalog. Read the linked science articles for the research behind each compound.

1. Cellular Longevity Protocol

Goal: Restore the NAD⁺ levels that decline with age, reactivate the sirtuin enzymes that depend on it, and protect mitochondria from oxidative damage. This is the foundational longevity stack popularized by Harvard’s Dr. David Sinclair.

The stack

• Longevity Stack Bundle — NMN 500 mg + Resveratrol 600 mg, packaged together for 30 days
• CoQ10 400 mg — the cofactor that powers ATP production inside mitochondria
• Astaxanthin 12 mg — a fat-soluble antioxidant that crosses cell membranes most others can’t
• Spermidine 10 mg — induces autophagy, the cellular renewal pathway that clears damaged mitochondria so the rest of the stack has clean machinery to work with
• Fisetin 500 mg — a senolytic flavonoid that helps clear out senescent "zombie" cells; the mechanism Spermidine doesn't touch (autophagy recycles healthy cells; fisetin removes the ones too damaged to recycle)
• Quercetin 500 mg — the second senolytic flavonoid; Quercetin is the "Q" in the Mayo Clinic's D+Q protocol — the first senolytic combination tested in humans — and it adds an NF-κB-driven anti-inflammatory layer that fisetin alone doesn't cover
• TMG 1000 mg — replaces the methyl groups the body burns to clear nicotinamide (the breakdown product of NMN), keeping the SAMe pool full so DNA methylation, neurotransmitter synthesis, and homocysteine clearance keep running normally; the consensus pairing for anyone taking NMN long-term
• Apigenin 50 mg — inhibits CD38, the enzyme that destroys NAD⁺ and whose activity rises sharply with age; while NMN feeds production, apigenin slows the leak on the other side of the cycle, so more of what you make stays around long enough to be used
• Curcumin 1000 mg + BioPerine — the inflammation layer most longevity stacks miss; inhibits NF-κB (the master inflammation switch that drives inflammaging at the tissue level) while activating Nrf2, which turns on the body's own antioxidant production — glutathione, superoxide dismutase, catalase. Standardized to 95% curcuminoids with BioPerine for up to 2000% better absorption
• Urolithin A 500 mg — the mitophagy layer; specifically up-regulates the PINK1/Parkin pathway that tags broken, leaky mitochondria for recycling so the cell can build new ones. Spermidine triggers general autophagy and the senolytics clear whole damaged cells; Urolithin A targets the dysfunctional mitochondria inside healthy cells — the population that doesn't make energy but does make reactive oxygen species. Most people's gut bacteria can't produce it from pomegranate, so direct supplementation is the only reliable route
• PQQ 20 mg — the biogenesis layer; the only widely-studied compound shown to create new mitochondria from scratch via the PGC-1α pathway, the same master regulator exercise activates. Where Urolithin A clears the broken mitochondria, PQQ stimulates the cell to build replacements. Pairs directly with CoQ10 (PQQ creates the new mitochondria, CoQ10 powers the electron-transport chain inside them); the two are increasingly tested together in cognition trials with consistent benefit
• Magnesium Glycinate 400 mg — the foundation underneath every other compound in this protocol. NAMPT (the enzyme that converts NMN into NAD⁺) is magnesium-dependent. So is the SAMe methylation cycle that TMG supports, the Vitamin D activation pathway, and the GABA-A receptor that initiates the deep sleep when most cellular renewal actually happens. Roughly two-thirds of American adults are below the RDA, and the soft signs — poor sleep, muscle cramps, eyelid twitches, anxiety floor — are common enough we've stopped recognizing them as deficiency. Bisglycinate chelate is the form used in clinical sleep and methylation research; ~80% absorption with no laxative effect, plus glycine's own GABA-promoting role at the spinal level
• Vitamin D3 5000 IU + K2 MK-7 100 mcg — the second foundational layer alongside magnesium. Roughly 40% of US adults run below 20 ng/mL serum 25(OH)D — clinically deficient — and another 40% sit in the "insufficient" band linked to higher all-cause mortality. D3 controls roughly 200 genes covering immune surveillance, insulin sensitivity, mood, and bone density, but only after magnesium activates it into its hormone form (calcitriol) — which is why this pair belongs together at the base of the protocol. K2 (MK-7 form, 72-hour half-life) directs the calcium D3 mobilizes into bone and teeth rather than soft tissue, arteries, and kidneys; the Rotterdam Study showed adults with the highest K2 intake had 50% lower cardiovascular mortality and 25% lower all-cause mortality. Without K2, high-dose D3 is a calcification risk; with it, you get the longevity upside of correcting deficiency without depositing calcium where it doesn't belong
• Ashwagandha KSM-66 600 mg — the cortisol/HPA-axis layer underneath the foundational chemistry. Chronic high cortisol is the single most leveraged failure mode in this protocol: it activates CD38 (the enzyme that degrades NAD⁺), inhibits NAMPT (the enzyme that builds it), suppresses the autophagy that Spermidine is trying to induce, accelerates the senescent-cell accumulation that Fisetin and Quercetin are trying to clear, and degrades the slow-wave sleep where most cellular repair actually happens. KSM-66 is the standardized root extract used in the majority of the published cortisol RCTs — Chandrasekhar 2012 saw a 27.9% drop in serum cortisol at 600 mg/day over 60 days, with parallel sleep-architecture, anxiety, and strength outcomes in follow-up trials. This is the input layer that determines whether the rest of the stack runs in repair mode or runs through a body still pushing emergency response
• Omega-3 Fish Oil 2000 mg (720 EPA + 480 DHA) — the third leg of the foundational trio with Magnesium and Vitamin D3+K2. EPA and DHA are essential fatty acids the body cannot make in meaningful quantities, and the conversion from plant-source ALA is <10% for EPA and <1% for DHA — so without fish or supplementation, the cellular machinery the rest of this stack runs on is built on the wrong substrate. Three concrete reasons it belongs at the base, not as a separate goal: (1) the inner mitochondrial membrane is roughly 20% cardiolipin, a phospholipid whose composition determines how efficiently the electron transport chain runs — DHA-enriched cardiolipin produces more ATP per oxygen consumed and oxidizes less under load, meaning CoQ10 and PQQ work better in mitochondria built on the right lipids; (2) EPA and DHA are the substrate for resolvins, protectins, and maresins (the SPM family), the body's own signal molecules that actively resolve inflammation rather than just block it — the missing complement to Curcumin and Quercetin's NF-κB suppression; (3) every cell membrane in the body is a fatty-acid bilayer whose fluidity determines how receptors function — the same NAD⁺, sirtuin, and AMPK signaling the rest of the stack targets runs through membranes whose responsiveness is set by their omega-3 content. The omega-3 index target for longevity research is >8% of red cell membrane fatty acids; most untreated Westerners sit at 4–5%. Wild-caught (anchovy/sardine/mackerel — the small forage species low in mercury), triglyceride form, molecularly distilled, enteric-coated for no fishy reflux
• Alpha-Lipoic Acid 600 mg — the universal antioxidant + cofactor layer. ALA is unusual in being both water- and fat-soluble, so it crosses freely between bloodstream, cytoplasm, mitochondrial matrix, cell membrane, and the blood-brain barrier — most other antioxidants are restricted to one compartment. It also regenerates oxidized Vitamin C, Vitamin E, glutathione, and CoQ10 back to their active forms, so the rest of the antioxidant network in this stack runs longer per dose. Underneath the antioxidant role, ALA is the direct cofactor of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase — two of the enzyme complexes that decide how efficiently glucose enters the Krebs cycle to produce the NADH that NMN-fed NAD⁺ cycling depends on. Bruce Ames's group at UC Berkeley built the founding rodent-longevity work of the modern field on the ALA + acetyl-L-carnitine combination; 600 mg/day is the trial-validated dose
• Taurine 1000 mg — the fifth foundational nutrient layer alongside Magnesium, D3+K2, and Omega-3. Taurine is a sulfur-containing amino acid the body uses for cardiovascular ion handling, bile acid conjugation, GABA-A modulation, and — the mechanism most longevity discussions miss — chemical modification of two specific mitochondrial tRNAs (tRNA-Leu and tRNA-Lys). Without enough taurine, those tRNAs misread their codons and the mitochondrial-encoded subunits of Complex I and Complex IV get assembled incorrectly, lowering ATP output and raising reactive oxygen species — exactly the pattern aged tissue shows. The June 2023 Science paper by Singh and Yadav (Taurine deficiency as a driver of aging) measured taurine across the lifespan in monkeys, mice, and humans and found roughly 80% of youthful blood concentrations are gone by middle age; supplementing middle-aged mice for the rest of their lives extended lifespan ~10–12% with better-preserved muscle mass, lower cellular senescence, and lower fasting glucose. NMN feeds NAD⁺, CoQ10 powers the chain, PQQ builds the population, Urolithin A clears the broken ones — Taurine ensures the mitochondrial proteins inside that population are assembled correctly in the first place. Vegan-fermented L-taurine, no animal-derived bile
• Creatine Monohydrate 1000 mg — the tissue-level energy buffer in front of every mitochondrial lever above it. Phosphocreatine regenerates ATP from ADP instantly — faster than mitochondria can produce it from scratch — which is why the body relies on the buffer for any short, high-demand event: a muscle contraction, a neuron firing rapidly, a heart beat under load. NMN raises the steady-state ATP ceiling; CoQ10 and PQQ optimize how mitochondria run; creatine sits one step downstream as the immediate-availability reserve cells actually pull from when demand spikes. The longevity-relevant case is sarcopenia: roughly 30% of muscle mass is lost between ages 40 and 80 if nothing intervenes, and skeletal muscle index is one of the strongest single predictors of all-cause mortality after 65 — comparable to LDL or systolic BP at that age. The Devries & Phillips 2014 meta-analysis of 357 elderly subjects found creatine plus resistance training added ~1.4 kg of lean mass and meaningfully more strength than training alone; Chilibeck 2015 showed it preserved postmenopausal femoral neck bone density over 12 months. The cognitive evidence is now equally serious — Rae 2003 (working memory and reasoning) and McMorris 2007 (sleep-deprivation rescue) both replicate, with the largest effects in stressed, vegetarian, and aging populations whose baseline brain creatine is lower. The dose hasn't moved in thirty years: 5 g/day. Micronized, ≥99.9% pure, Creapure-grade equivalent
• Calcium Alpha-Ketoglutarate (CaAKG) 1000 mg — the substrate-level lever sitting underneath the epigenetic clocks the rest of this stack tries to slow down. α-Ketoglutarate is the central pivot of the Krebs cycle (every nutrient that fuels your cells passes through it) and the required co-substrate for two enzyme families that decide what your epigenome actually looks like: TET1/2/3 (which demethylate cytosine in DNA) and the JmjC histone demethylases (which strip methyl marks off histones). These are the enzymes that reset the Horvath, GrimAge, and PhenoAge epigenetic clocks. α-KG levels drop roughly an order of magnitude across the human lifespan; the Buck Institute's 2020 mouse study (Asadi Shahmirzadi et al., Cell Metabolism) showed CaAKG supplementation extended median lifespan and compressed end-of-life morbidity, and the 2021 TruDiagnostic human pilot (Demidenko et al., Aging) lowered DNAm GrimAge by an average of 8 years over 7 months at 1000 mg/day — the first published longevity supplement with measurable epigenetic-clock reversal in humans. NMN raises NAD⁺ and the sirtuins use it to reset chromatin marks, but the demethylase enzymes that strip off the old marks still need α-KG to do their work; CaAKG is what gives them the substrate. The calcium portion (~200 mg elemental per capsule, about a fifth of the RDA) is the carrier — directed into bone matrix rather than artery wall by the K2 MK-7 already in the foundational layer above.

Daily schedule

• Before breakfast (empty stomach): 1 Alpha-Lipoic Acid (absorbs best fasted; food drops bioavailability ~30%)
• Morning, with breakfast: 1 NMN + 1 Resveratrol + 1 CoQ10 + 1 Astaxanthin softgel + 1 Spermidine + 1 Fisetin + 1 Quercetin + 1 TMG + 1 Apigenin + 1 Curcumin + 1 Urolithin A + 1 PQQ capsule + 1 Magnesium Glycinate + 1 Vitamin D3+K2 softgel + 1 Omega-3 softgel + 1 Taurine capsule + 5 Creatine capsules (5 g) + 1 Ashwagandha KSM-66 (with food) + 1 CaAKG (with food)
• Evening, 60–90 minutes before bed: 1 Magnesium Glycinate (the second half of the split-dose magnesium protocol — supports sleep architecture and overnight cellular repair). Ashwagandha is moved to the AM dose by default; if sleep is the priority outcome, shift the Ashwagandha capsule to this evening slot instead — the Langade 2019/2020 sleep-architecture trials all used PM dosing.
• Resveratrol, CoQ10, Quercetin, Apigenin, Curcumin, Urolithin A, PQQ, Vitamin D3+K2, and Omega-3 — take with a meal that contains some fat for better absorption (Omega-3 absorbs roughly 3× better with food than on an empty stomach).

Why these together

NMN raises NAD⁺. Resveratrol activates the sirtuin enzymes that use that NAD⁺ to repair DNA. CoQ10 sits at the end of the electron-transport chain — if NAD⁺ is the fuel, CoQ10 is the spark plug. Astaxanthin protects all three from being burned up by free radicals along the way. Spermidine inducing autophagy keeps healthy cells running cleanly by clearing worn-out mitochondria. Fisetin and Quercetin close the last loop — they trigger apoptosis in cells that are too damaged to recycle, so they stop leaking inflammatory signals into the tissue around them. Quercetin and Fisetin are the same drug class with different specialties: Fisetin is more potent per milligram and crosses into brain tissue; Quercetin is the better-validated human senolytic and adds an antihistamine and NF-κB-suppressing bonus mechanism. TMG closes a different loop again — it doesn't fight aging directly, it protects the rest of the stack. Every dose of NMN burns through methyl groups when the body clears its breakdown product. Over months that drains the SAMe pool that drives DNA methylation, neurotransmitter synthesis, and homocysteine clearance. TMG replaces the methyl groups the protocol consumes, so the upstream half of the stack keeps working cleanly. Apigenin closes the last loop on the NAD⁺ side specifically — by inhibiting CD38, it slows the enzyme that breaks NAD⁺ back down. CD38 activity rises several-fold between ages 20 and 60, and the Mayo Clinic group has shown it is the dominant driver of age-related NAD⁺ loss. NMN feeds production. TMG keeps the cleanup machinery running. Apigenin protects the molecule itself once it's made. Curcumin works one layer up — it dials back the chronic, low-grade NF-κB inflammation that ages tissue regardless of how clean your mitochondria are, and activates Nrf2 so the body produces more of its own glutathione and antioxidant enzymes. You can have perfect NAD⁺ output and still age fast if your tissues sit in a constant inflammatory simmer; curcumin closes that gap. Urolithin A closes the last gap — the population of mitochondria themselves. Spermidine triggers general autophagy. The senolytics clear whole senescent cells. But inside otherwise healthy cells, damaged mitochondria accumulate with age — leaky, depolarized, low-output organelles that don't produce ATP but do produce reactive oxygen species. Urolithin A is the most-studied molecule shown in human muscle biopsies to up-regulate mitophagy genes (PINK1/Parkin) and clear that broken population so the cell can replace it. NMN feeds new mitochondria. CoQ10 sparks the working ones. Urolithin A removes the broken ones to make room. PQQ closes the cycle on population — it's the only compound in the stack that directly stimulates the cell to build new mitochondria from scratch, by activating PGC-1α (the same master regulator exercise turns on). Mitochondrial density in skeletal muscle is roughly half at age 70 what it was at 20; clearing broken ones makes room, but something has to actually grow the new population. PQQ is that lever. Magnesium sits underneath all of it — not as another lever, but as the cofactor that lets the levers work. NAMPT can't convert NMN to NAD⁺ without it. The SAMe methylation cycle TMG supports is a magnesium-dependent reaction. ATP itself circulates as Mg-ATP; without sufficient magnesium the energy your mitochondria produce is harder for the cell to actually use. And the deep, slow-wave sleep when autophagy, glymphatic clearance, and growth-hormone-driven repair actually happen runs through GABA pathways that magnesium glycinate is one of the cleanest ways to support. Most longevity stacks ignore this layer because magnesium isn't novel; it's also why two-thirds of supplemented people don't get the response the rest of the stack should produce. Each compound covers a different failure mode of aging; magnesium covers the chemistry that runs them all. Vitamin D3 and K2 sit on the same foundation as magnesium — not levers, but the upstream conditions everything else depends on. Roughly 80% of US adults run below the 25(OH)D level the longevity-research consensus targets (40–60 ng/mL); without sufficient D3, the immune surveillance that clears senescent cells doesn't run cleanly, insulin sensitivity drifts off, and bone metabolism leaks calcium into places it doesn't belong. Magnesium activates D3 into its hormone form, then K2 (MK-7) directs the calcium D3 mobilizes into bone rather than artery — closing the loop the deficient-D3 / no-K2 combination opens. Omega-3 closes the foundational triangle with Mg and D3+K2 — not as a discrete lever, but as the substrate the rest of the protocol's machinery is built out of. The inner mitochondrial membrane is roughly 20% cardiolipin, a phospholipid whose composition determines how efficiently NMN-fueled NAD⁺ actually translates into ATP; DHA-enriched cardiolipin runs the electron-transport chain more efficiently and is more resistant to peroxidation than the omega-6-dominant version a Western diet produces, so CoQ10 and PQQ both work better in mitochondria built on the right lipids. EPA and DHA are also the precursors to resolvins, protectins, and maresins — the SPM family that resolves inflammation downstream of where Curcumin and Quercetin block it, hitting both ends of the inflammaging loop. And every receptor in the cell, including the ones that pull in NMN and other precursors, sits in a membrane whose fluidity is set by its omega-3 content. The Mg + D3 + K2 + Omega-3 quartet is the foundational chemistry the headline molecules sit on top of; the senolytics and CD38 inhibitors and mitophagy activators all work better in a body whose foundational mineral, vitamin, and fatty-acid status is intact. Alpha-lipoic acid sits in a slightly different role from the foundational quartet — it's the only molecule in the stack that is simultaneously an antioxidant, a regenerator of other antioxidants, and a direct cofactor inside the Krebs cycle. The practical consequence is that every dose of Vitamin C, Vitamin E, glutathione, and CoQ10 in the stack effectively goes further when ALA is in circulation, because each of those compounds gets put back into rotation rather than being a single-use molecule. And on the mitochondrial side, ALA sits inside the upstream substrate handoff that determines how efficiently the glucose entering the cell becomes the NADH that feeds NAD⁺ cycling, the ATP that the cell actually uses, and the substrate the rest of the protocol's NAD⁺/sirtuin/AMPK signaling runs on. The Bruce Ames lab at UC Berkeley built the founding rodent-longevity work of the modern field around exactly this molecule for exactly this reason.

Calcium Alpha-Ketoglutarate sits one layer underneath even the foundational quintet — at the substrate level the epigenetic-reset machinery itself depends on. NMN raises NAD⁺. Resveratrol, Apigenin, and the sirtuin chemistry above use that NAD⁺ to add and remove methyl marks on histones. But the actual removal of old methyl marks runs through the JmjC histone demethylase family and the TET1/2/3 DNA demethylases — and every member of both families is α-ketoglutarate dependent. Without enough α-KG, those enzymes simply can't catalyze the demethylation reaction the rest of the protocol's epigenetic-remodeling logic assumes is happening. The Buck Institute lifespan study and the TruDiagnostic 8-year GrimAge reversal both ran on the same 1000 mg/day CaAKG dose; both pointed at the same mechanism: refilling the substrate that the demethylase enzymes need to do their work. The Krebs-cycle bonus mechanism — α-KG sits between isocitrate and succinyl-CoA in the citric acid cycle, generating the NADH that drives Complex I — gives the protocol an upstream Krebs-cycle entry point that complements ALA's downstream substrate-handoff role and Taurine's mitochondrial tRNA-modification role. The protocol now covers four distinct mitochondrial layers explicitly: substrate input (CaAKG into the Krebs cycle), enzyme-cofactor handoff (ALA), mt-tRNA modification (Taurine), and electron-transport completion (CoQ10 + PQQ + Urolithin A) — meaning the production side of the bioenergetic chain is intact at every step a single missing molecule could break.

Read the science: What Is NAD⁺? · NMN vs NAD⁺ · Why Resveratrol Belongs in the NMN Stack

2. Beauty & Skin Protocol

Goal: Rebuild the collagen matrix that makes skin firm, restore the hydration that makes it plump, and protect against the UV and pollution stress that breaks both down.

The stack

• Beauty & Longevity Stack — Marine Collagen + Biotin + Hyaluronic Acid + Vitamin C, all in one bundle
• Astaxanthin 12 mg — clinically shown to improve skin elasticity and reduce fine lines after 8 weeks
• Glutathione 500 mg — the master antioxidant that brightens uneven tone and protects collagen from oxidation
• Calcium Alpha-Ketoglutarate (CaAKG) 1000 mg — the substrate behind collagen assembly. Marine collagen peptides give the body the amino acid building blocks (glycine, proline, hydroxyproline). But the enzymes that crosslink those amino acids into stable triple-helix collagen — prolyl-4-hydroxylase and lysyl hydroxylase — are both α-ketoglutarate dependent. Without sufficient α-KG, collagen synthesis is rate-limited regardless of how much peptide you ingest. CaAKG also fuels the JmjC and TET demethylases that maintain dermal fibroblast youthfulness as skin ages — the same epigenetic-reset mechanism the Cellular Longevity Protocol leans on, applied to the cells that actually make your skin

Daily schedule

• Morning: 1 scoop Marine Collagen in coffee or smoothie + 1 Biotin + 2 Hyaluronic Acid + Vitamin C capsules + 1 CaAKG capsule
• Evening: 1 Astaxanthin softgel + 1 Glutathione capsule on an empty stomach (30 minutes before food)

Why these together

Collagen and biotin give your body the raw materials to build skin and hair. Hyaluronic acid pulls water into the dermis so it looks plump rather than dry. Astaxanthin and glutathione protect what you just built — without antioxidant cover, UV and pollution oxidize collagen as fast as you can make it. CaAKG closes the assembly side of the loop the rest of the stack feeds into: marine collagen supplies the amino-acid bricks, hyaluronic acid pulls in water, antioxidants protect the result — but the enzymes that actually crosslink those bricks into stable collagen (prolyl-4-hydroxylase and lysyl hydroxylase) are α-ketoglutarate dependent, and aged skin runs them on a falling substrate supply. Refilling α-KG is what lets the rest of the inputs be assembled rather than excreted.

Read the science: Marine vs Bovine Collagen · Topical vs Oral Hyaluronic Acid · Glutathione for Skin Brightening

3. Metabolic Health Protocol

Goal: Steady blood sugar, support insulin sensitivity, and reduce the metabolic drift that quietly accumulates after 35.

The stack

• Berberine HCL 500 mg — the plant alkaloid most often compared to metformin in clinical trials
• CoQ10 400 mg — mitochondrial cofactor; particularly important for anyone on statins
• Resveratrol 600 mg — activates AMPK, the same metabolic master switch berberine targets
• Alpha-Lipoic Acid 600 mg — the trial-validated metabolic dose. ALA increases GLUT4 translocation to the cell surface (the same downstream glucose-uptake pathway insulin and exercise both activate), so it lands in similar metabolic territory as berberine through a different molecular entry point. It's also the cofactor inside pyruvate dehydrogenase and α-ketoglutarate dehydrogenase — the two enzyme complexes that decide whether glucose actually gets burned for ATP versus shunted into lactate. The German neuropathy trials (ALADIN, DEKAN, NATHAN) used the same 600 mg/day dose this product matches
• Taurine 1000 mg — the cardiovascular and bile-conjugation foundation underneath the metabolic levers. Taurine is the most abundant free amino acid in the heart muscle (concentrations 100–400× plasma) and modulates the calcium handling, potassium flux, and vascular tone that decide how the cardiovascular system responds to glucose load. Sun et al. (Hypertension, 2016) showed 1.5–3 g/day reduced systolic blood pressure 5–10 mmHg in mild-to-moderate hypertension over 6–12 weeks. On the lipid side, taurine is one of the two amino acids the liver uses to conjugate bile acids — taurocholate and taurochenodeoxycholate are more soluble at duodenal pH, recycle more efficiently through the enterohepatic loop, and modestly improve LDL clearance (5–10% drop in total cholesterol and LDL at 3 g/day in obese-subject trials). And on the mitochondrial side, taurine is the cofactor that lets mitochondrial tRNAs modify correctly so the electron transport chain assembles right — the same chain CoQ10 keeps powered. Plasma taurine drops ~80% between age 5 and age 60 (Singh & Yadav, Science 2023), and the metabolic deterioration that pattern correlates with is the same drift this protocol targets
• Before lunch: 1 Berberine + 1 CoQ10 (with food, fat-soluble)
• Before dinner: 1 Berberine + 1 Resveratrol + 1 Taurine
• Berberine is best taken 15–30 minutes before your largest carbohydrate meals.

Why these together

Berberine and resveratrol both flip the AMPK switch — the cellular signal that tells your body to burn glucose rather than store it. CoQ10 keeps the mitochondria that do that burning at full capacity, and replaces what statin medications deplete. Alpha-lipoic acid closes the loop two layers down: it improves GLUT4 trafficking at the receptor level (so glucose actually moves out of the bloodstream and into muscle cells), then sits as a cofactor inside the Krebs cycle that converts that glucose into ATP. The German clinical literature on ALA at 600 mg/day is a separate evidence base from the metformin-comparison work on berberine; layered together you get AMPK activation upstream, GLUT4 trafficking at the membrane, and clean substrate handoff into the mitochondria — three molecular entry points into the same metabolic destination, which is why modern metabolic-health stacks rarely use berberine alone.

Read the science: Berberine vs Metformin · CoQ10 & Statins

4. Fertility & Cellular Energy Protocol

Goal: Support egg and sperm quality by improving the mitochondrial energy that drives every cell division — and that’s the bottleneck for fertility after age 35.

The stack

• CoQ10 400 mg — the most-studied fertility supplement of the past decade; recommended in many fertility clinics
• PQQ 20 mg — the biogenesis pair to CoQ10; while CoQ10 powers the existing mitochondria inside the egg, PQQ stimulates the creation of new ones via PGC-1α. Oocytes contain roughly 100,000 mitochondria — the most of any cell type in the body — and the early embryo runs entirely on the mother's mitochondrial ATP until implantation. Sperm motility is similarly dependent on mitochondrial output: the sperm tail is essentially a mitochondrial engine. The CoQ10 + PQQ combination is increasingly recommended in fertility-focused supplement protocols for exactly this reason
• Pure NMN 500 mg — rebuilds NAD⁺, which mitochondria need to make ATP
• Astaxanthin 12 mg — protects gametes from oxidative damage during the 90-day maturation window
• Creatine Monohydrate 1000 mg — the phosphocreatine layer that buffers ATP at the millisecond timescale gametes actually need it. Sperm motility is essentially a mitochondrial-engine problem (the sperm tail runs on ATP supplied by the midpiece's mitochondrial sheath); randomized human trials including Stanislavov 2018 have measured improvements in progressive motility with creatine supplementation alongside CoQ10. The egg side is the energetic mirror: the oocyte enters fertilization carrying all of the mitochondria the early embryo will use until implantation, and the ATP buffer those mitochondria can draw on is what determines whether meiotic spindles assemble correctly during the chromosome-segregation steps that fail more often after 35. CoQ10 and PQQ work upstream on the mitochondrial side; creatine sits downstream as the immediate-energy reserve gametes pull from when demand spikes. Pairs particularly cleanly with the rest of this protocol because all four compounds operate on the same energy axis at different layers — substrate, biogenesis, electron transport, immediate buffer
• Calcium Alpha-Ketoglutarate (CaAKG) 1000 mg — the substrate layer underneath the four-mechanism energy chain above. The oocyte's ~100,000 mitochondria are the entire energy reserve the early embryo runs on until implantation; every one of them is running the Krebs cycle, and α-ketoglutarate is the cycle's central pivot — the substrate that α-KG dehydrogenase converts into succinyl-CoA, generating the NADH that feeds the electron transport chain CoQ10 keeps powered. Plasma α-KG drops roughly 10-fold across the human lifespan (Liu et al., Aging Cell 2018), and the same age window where oocyte quality and meiotic-spindle assembly accuracy decline is the window where the substrate the spindle's energy supply depends on is running out. The Buck Institute lifespan study and the 2021 TruDiagnostic GrimAge reversal both ran on the same 1000 mg/day dose this product matches. The second mechanism that matters here is epigenetic: gametes carry methylation patterns that are reset and re-established during the 90-day maturation window, and the TET / JmjC demethylase enzymes that do that resetting are α-KG dependent — running them on inadequate substrate is one of the molecular reasons advanced-maternal-age oocytes carry more methylation noise. CaAKG fills the substrate side of both mechanisms (Krebs-cycle fuel and demethylase substrate) — the levers the rest of the protocol assumes are intact

Daily schedule

• Morning, with breakfast: 1 CoQ10 + 1 PQQ + 1 NMN + 1 Astaxanthin softgel + 5 Creatine capsules (5 g) + 1 CaAKG capsule
• Run continuously for at least 90 days — the full sperm and egg maturation cycle. CaAKG works at the substrate level and is silent week-to-week — consistency at 1 capsule/day for the full 90 days is what the Krebs-cycle and epigenetic-substrate mechanisms require.

Why these together

Egg and sperm quality after 35 is fundamentally an energy problem — mitochondrial NAD⁺ and CoQ10 both fall, ATP production drops, and cell division becomes more error-prone. CoQ10 powers the mitochondria already inside the developing egg or sperm. PQQ stimulates the cell to build new mitochondria via PGC-1α — directly relevant because the oocyte's roughly 100,000 mitochondria are the entire energy reserve the early embryo runs on until implantation. NMN feeds the NAD⁺ those mitochondria need for ATP. Astaxanthin is the membrane-soluble antioxidant that shields the whole system from the oxidative damage that accumulates during the 90-day maturation window. Restore the substrates, build new mitochondrial population, protect what you've built — and creatine adds the fifth layer the original four-product version was missing: the phosphocreatine buffer that regenerates ATP from ADP at the timescale meiotic spindles, sperm motility, and embryonic cleavage divisions actually run on. The CoQ10 + PQQ + NMN trio raises the production ceiling; creatine raises the immediate-availability floor. CaAKG closes the substrate side that the entire production-and-buffer machinery sits on top of — the α-ketoglutarate that the Krebs cycle in every oocyte mitochondrion converts into the NADH the electron transport chain runs on, and the same α-KG that the TET/JmjC demethylases need to reset oocyte methylation patterns during the 90-day maturation window. CoQ10 + PQQ + NMN + Creatine + CaAKG covers five distinct layers — biogenesis (PQQ), substrate (CaAKG), NAD+ pool (NMN), electron transport (CoQ10), and the phosphocreatine buffer (Creatine) — meaning the bioenergetic chain is intact at every step the meiotic-spindle and sperm-motility machinery actually depends on. That's the protocol.

Important: Always tell your fertility doctor what supplements you’re taking. These compounds are well-studied but interact with some IVF protocols.

5. Immunity & Antioxidant Protocol

Goal: Strengthen the body’s antioxidant defense system — the layer that determines how well your immune cells perform under stress, lack of sleep, or seasonal pressure.

The stack

• Liposomal Vitamin C 1000 mg — absorbs at roughly twice the rate of standard vitamin C
• Glutathione 500 mg — the body’s primary intracellular antioxidant
• Astaxanthin 12 mg — closes the gap by protecting the cell membranes vitamin C can’t reach
• Quercetin 500 mg — stabilizes mast cells (the immune cells that release histamine) and inhibits NF-κB-driven inflammation; the layer most antioxidant stacks miss
• Curcumin 1000 mg + BioPerine — the second NF-κB inhibitor in the stack, hitting the same pathway as Quercetin through a different mechanism, plus Nrf2 activation that turns on endogenous glutathione and antioxidant enzyme production — so the stack supports both the antioxidants you take and the ones your body makes itself
• Vitamin D3 5000 IU + K2 MK-7 100 mcg — the foundational layer the antioxidant stack assumes you already cover. Vitamin D receptors sit on virtually every immune cell; the 2020 BMJ meta-analysis of 25 RCTs found D3 supplementation cut acute respiratory infection risk by 12% overall, and 70% in adults who started below 25 nmol/L serum 25(OH)D. Mechanism: upregulation of cathelicidin and defensin antimicrobial peptides plus modulation of regulatory T-cells. K2 (MK-7) is included because high-dose D3 without K2 is a cardiovascular calcification risk; together they're the immune-foundation pair, not just bone insurance
• Omega-3 Fish Oil 2000 mg (720 EPA + 480 DHA) — the resolution side of inflammation that the rest of the stack only blocks. Curcumin and Quercetin both inhibit NF-κB upstream — they reduce the inflammatory signal. EPA and DHA are the substrates the body uses to build resolvins, protectins, and maresins (the SPM family) — the signal molecules that actively resolve inflammation once the threat is cleared, returning the tissue to baseline rather than leaving it in chronic low-grade simmer. SPMs only get made when the EPA/DHA substrate is available, which it almost never is on a Western diet running 15–20:1 omega-6:omega-3. Beyond that, EPA and DHA stabilize immune cell membranes (the same mechanism Quercetin uses on mast cells but applied to every white cell), and DHA modestly amplifies Vitamin D's effect on regulatory T-cells. Triglyceride form, molecularly distilled, enteric-coated for no fishy reflux. The omega-3 index target for immune-research and longevity-research benefit is >8% of red cell membrane fatty acids; most untreated Westerners sit at 4–5%

Daily schedule

• Morning: 1 Liposomal Vitamin C + 1 Astaxanthin softgel + 1 Quercetin + 1 Curcumin capsule + 1 Vitamin D3+K2 softgel + 1 Omega-3 softgel (with a meal containing some fat — D3+K2, Astaxanthin, Curcumin, and Omega-3 are all fat-soluble)
• Evening: 1 Glutathione capsule on an empty stomach
• For seasonal allergies, double Quercetin to twice daily two weeks before peak season — taken with the morning vitamin C, since vitamin C regenerates oxidized quercetin back into its active form.

Why these together

Vitamin C, glutathione, and astaxanthin sit in different parts of the cell — water-soluble plasma, water-soluble cytoplasm, and fat-soluble membrane respectively — so they cover oxidative stress everywhere it shows up. Vitamin C also recycles glutathione back to its active form, so the two are stronger together than either alone. Quercetin adds a different mechanism the others don’t touch: it stabilizes the membrane of mast cells so they release less histamine, and inhibits NF-κB so the chronic, low-grade inflammation that suppresses immune function gets dialed back. Vitamin C and Quercetin also recycle each other — vitamin C reduces oxidized quercetin back into its active form, extending its half-life in plasma. Curcumin doubles up on Quercetin's NF-κB suppression by hitting the pathway through a different mechanism, and adds Nrf2 activation — the master switch that turns on the body's own production of glutathione and antioxidant enzymes. The result is a stack that supports both the antioxidants you take in and the ones your body makes itself. Vitamin D3 sits underneath all of it — not as another antioxidant, but as the hormone that determines whether your immune cells can actually use what the rest of the stack provides. Around 80% of US adults run below the 25(OH)D level the immune-research consensus targets, and respiratory infection rates climb sharply through that gap; D3 supplementation cut respiratory infections by 70% in deficient adults in the largest RCT meta-analysis to date. K2 is paired in to direct the calcium D3 mobilizes into bone rather than artery — making the dose safe at the levels actually needed to move serum status into the longevity band. Omega-3 closes the loop the rest of the stack only opens. Curcumin, Quercetin, and Vitamin C all block the inflammatory signal upstream — useful, but only half the system. The other half is resolution: EPA and DHA are the precursor substrates the body uses to build resolvins, protectins, and maresins, the signal molecules that actively return tissue to baseline once a threat is cleared instead of leaving it smoldering. SPMs only get made when the substrate is present, and on a Western diet running 15–20:1 omega-6:omega-3 it almost never is. Most antioxidant stacks ignore this layer; without it, you can suppress inflammation all day and never resolve any of it. The full immunity stack — antioxidants in every cellular compartment (vitamin C / glutathione / astaxanthin), inflammation suppression by two distinct mechanisms (quercetin, curcumin), endogenous-antioxidant activation (curcumin's Nrf2 induction), the immune-cell-receptor hormone (vitamin D3+K2), and the resolution substrate (omega-3) — is the closest thing the catalog has to a complete picture of how a healthy immune system actually regulates itself.

6. Advanced NAD⁺ Protocol

Goal: Maximum NAD⁺ restoration for people who already know their baseline stack and want to push it further. This is the protocol for someone who has run NMN + Resveratrol for 12+ weeks and wants the next level.

The stack

• Liposomal NAD⁺ Ultimate 1000 mg — direct NAD⁺, encapsulated to survive digestion
• NAD⁺ 5-in-1 Complete Mitochondrial Formula — NAD⁺ stacked with quercetin, fisetin, trans-resveratrol, and PQQ
• NMN 1000 mg Double Strength — the precursor your liver uses to keep NAD⁺ high all day
• TMG 1000 mg — replaces the methyl groups burned clearing nicotinamide; mandatory for anyone running NAD⁺ precursors at this dose long-term
• Apigenin 50 mg — inhibits CD38, the enzyme that destroys NAD⁺; the third leg of a complete advanced NAD⁺ protocol alongside the precursor and methyl donor — protect what you produce
• Urolithin A 500 mg — clears the damaged mitochondria that consume NAD⁺ without producing ATP; the missing fifth lever, because feeding more NAD⁺ into a population of broken mitochondria mostly produces reactive oxygen species. Urolithin A is the most studied molecule shown in human muscle biopsies to up-regulate mitophagy genes (PINK1/Parkin) so the cell can replace its mitochondrial population with healthier ones
• Magnesium Glycinate 400 mg — the cofactor underneath the entire pathway, and the most overlooked variable in NAD⁺-precursor protocols. NAMPT (NMN → NAD⁺) is magnesium-dependent; the SAMe cycle TMG supports is magnesium-dependent; ATP only circulates in its biologically active form as Mg-ATP. At 1000 mg of NMN per day the methylation throughput — and therefore the magnesium burn — is roughly double a starter protocol. Running this stack on insufficient magnesium is one of the most common reasons high-dose NMN users report flat results despite expensive precursors. Bisglycinate chelate, ~80% absorption, no laxative effect, supports the sleep architecture during which most of the cellular work the protocol pays for actually happens

Daily schedule

• Morning: 1 NMN 1000 mg + 1 NAD⁺ 5-in-1 capsule + 1 TMG + 1 Apigenin + 1 Urolithin A + 1 Magnesium Glycinate capsule with breakfast
• Mid-afternoon: 1 Liposomal NAD⁺ Ultimate (between meals for best absorption)
• Evening, 60–90 minutes before bed: 1 Magnesium Glycinate — the split-dose half supports sleep architecture and overnight repair, especially important at the higher methylation throughput this protocol creates

Why these together

You’re hitting NAD⁺ from five angles. The precursor (NMN) feeds production. Direct delivery (Liposomal NAD⁺) tops up tissue levels without waiting on the salvage pathway. The 5-in-1 layers in supportive senolytics (quercetin, fisetin) plus the sirtuin-activator resveratrol that puts the NAD⁺ to work. TMG and Apigenin are what make the high-dose protocol sustainable: TMG replaces the methyl groups the body burns clearing nicotinamide, and Apigenin slows CD38 — the enzyme whose age-rising activity drains NAD⁺ from the other side of the cycle. Urolithin A protects the destination — the mitochondria themselves. Pumping more NAD⁺ into a cell whose mitochondrial population is half broken doesn’t make energy; it mostly makes reactive oxygen species. Urolithin A activates mitophagy so the broken mitochondria are cleared and the cell builds new ones, giving the higher NAD⁺ output something working to feed. Without TMG and apigenin, doubling the precursor mostly drains your methyl pool and feeds an over-active degradation enzyme. Without Urolithin A, even a perfectly preserved NAD⁺ pool gets wasted on dysfunctional organelles. With all five layers, the high dose actually translates into measurable cellular renewal. Magnesium runs underneath all of it — NAMPT, the methylation cycle, and ATP usability all depend on it, and at 1000 mg/day of NMN the magnesium and methyl burn is roughly double a starter protocol. The split-dose magnesium (morning + evening) keeps the cofactor available for daytime conversion and the sleep architecture for overnight repair. This is not a starter stack — build up to it.

Read the science: Longevity Supplements After 40 · How to Stack Longevity Supplements · NMN vs NR

How to choose between protocols

Run one protocol at a time for at least 8–12 weeks before adding a second — that’s long enough to know what’s working and isolate any side effects to a single change. Most people start with the Cellular Longevity or Beauty & Skin protocol, then layer in a second once the baseline is comfortable.

Not sure where to begin? The Getting Started page walks you through choosing a primary goal in five minutes.

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any new supplement, especially if you are pregnant, nursing, on medication, or have a medical condition.