# Supplement Stack ##### ⚠️ !AVOID TAKING ASPIRIN, WARFARIN OR OTHER BLOOD-THINNING MEDICATION TOGETHER WHILE USING THIS STACK! ##### ⚠️ Warning: This is NOT medical advise. Always consult a medical professional when creating a supplement stack and using it. Science might change, and opinions vary. Some may interact with existing medications. We assume no liability, use at your own risk. ##### ⚠️ More is not always better. i.e. Resveratrol works optimal at 100-250mg. Above it might give you nosebleeds. The same may apply for other vitamins or substances. The list is not conclusive. --- ### Understanding nutraceutical risks and challenges "*Despite widespread use and assumed safety, emerging evidence challenges this assumption, revealing potential risks associated with nutraceuticals-particularly at high doses, during prolonged use, or in combination with other bioactive compounds. These risks arise through direct or indirect interactions with cellular systems, which may disrupt homeostasis, trigger oxidative stress, and dysregulate critical molecular pathways that can culminate in organ toxicity or metabolic dysfunction. In the United States, dietary supplements account for approximately 20% of drug-induced liver injuries, with nearly half attributed to combination products, highlighting the need to evaluate nutraceutical safety through the lens of cellular and molecular interactions.*" > Source: The double-edged sword of nutraceuticals: comprehensive review of protective agents and their hidden risks. > > Authors: Sahand Ashrafpour, M. Ashrafpour ## Supplement Use Good health is about balance-maintaining the body’s equilibrium without overtaxing it. Staying healthy is inherently difficult because it requires a delicate balance: applying just enough stress (such as exercise) to stimulate adaptation, without pushing the body into chronic inflammation. Supplementation follows the same principle. Supplements can be helpful, but they should be used cautiously to avoid unnecessary toxicity. Eating healthy is important, yet even there we must be mindful of excess exposure to toxins, pesticides, or pathogens. The truth is, we don’t fully understand how to balance all of this perfectly. The body constantly seeks homeostasis. Introducing a “beneficial” supplement can still disrupt that balance, even if it appears healthy in laboratory settings-curcumin is a good example. For this reason, a good rule of thumb is to use supplements in low doses: less is often better. Avoid prolonged, continuous use, and consider cycling supplements on and off. The goal of supplementation should be to gently support the body’s natural processes-helping to reduce inflammation, manage free radicals, and assist in clearing senescent cells-not to replace proper nutrition or “structurally feed” the body with supplements. What we do know is: that caloric restriction, intermitted fasting, sleep and brisk exercise is very good for our health. Always consult a medical professional before starting any supplement regimen. ## Supplement Stack - Luteoline - Quercetin (50mg/ day, every other month, with Vitamin C + E) - Resveratrol (100 to 250mg every day, or 500mg every other day) (+ Vitamin D and Omega 3) - Fisetin (little bit) - Omega 3 - Magnesium (glycinate) - CoQ10 - Brewers Yeast (deactivated) - Vitamin D3 - Vitamin C (not too much, risk of kidney stones if you do) - Nicotinamide (increase NAD+) - Piperlongumine - Ginger (extract or real) --- Dietary Restriction: only eat quality food, next to that clean supplements. ## Compound Overview ``` | Compound | Main Actions | Aging Hallmarks Targeted | Notes / Synergy | | ---------------------------- | ----------------------------------------------------------------- | ------------------------------------------------------------------------------------ | -------------------------------------------------------------- | | Luteolin | Anti-inflammatory, senomorphic (calms SASP), neuroprotective | Chronic inflammation, altered intercellular communication, cellular senescence | Works very well with quercetin; calming rather than aggressive | | Quercetin | Senolytic (moderate), anti-fibrotic, antioxidant | Cellular senescence, chronic inflammation, loss of proteostasis | Helps with connective tissue; absorption ↑ with vitamin C | | Resveratrol | SIRT1 activation, mitochondrial biogenesis, epigenetic regulation | Epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing | Take with fat; hormetic (don’t overdo dose) | | Fisetin (low dose) | Strong senolytic, anti-inflammatory | Cellular senescence, chronic inflammation | Potent - low dose & cycling is wise | | Omega-3 (EPA/DHA) | Anti-inflammatory, membrane fluidity, signaling | Chronic inflammation, altered intercellular communication, mitochondrial dysfunction | Synergistic with polyphenols; improves absorption | | Magnesium | ATP production, nervous system balance, sleep support | Mitochondrial dysfunction, genomic instability | Helps energy stability; supports vitamin D | | CoQ10 | Electron transport chain support, antioxidant | Mitochondrial dysfunction | Especially relevant after 40–50 | | Brewer’s yeast (deactivated) | B-vitamins, methylation, gut support | Epigenetic alterations, dysbiosis, deregulated nutrient sensing | Supports energy + microbiome | | Vitamin D3 | Immune modulation, anti-inflammatory | Chronic inflammation, altered intercellular communication | Works best with magnesium | | Vitamin C | Antioxidant, collagen synthesis, immune support | Genomic instability, loss of proteostasis | Improves quercetin uptake; supports connective tissue | ``` --- ## Cycling Protocol > ⚠️ Senolytics require caution: do NOT use it prolonged, if possible cycle them as prolonged senolytics use may upset natural balance and **increase** risks. Use the Senolytics in a hit and run. Like cycling it: one month supplements, then a month nothing. Because chronic supplementation might *increase* certain risks. ### A Clean Conceptual Model (not medical advice) ### Month ON Focus on: - Resveratrol - Quercetin - Fisetin (low dose) - Luteolin (senomorphic support) Goal: - Reduce senescent cell burden - Calm SASP / inflammation - "Reset" tissue environment ### Month OFF Keep: - Omega-3 - Magnesium - CoQ10 - Vitamin D - Vitamin C - Brewer's yeast Goal: - Repair - Regeneration - Mitochondrial recovery - Stem cell support This mirrors how the body naturally works: clear, rebuild, stabilize. --- ## Phase Overview ``` | Phase | Focus | Mechanisms Supported | | -----------------------------| ---------------------------------------------------------------| ----------------------------------------------------------------- | | ON month (senolytics active) | Quercetin, fisetin, luteolin | Reduce senescent cells, calm SASP, lower inflammation | | OFF month | Repair-focused stack: omega-3, magnesium, CoQ10, B-vitamins, D3, C | Mitochondria, stem cell recovery, DNA repair, tissue regeneration | | Every day | DR / intermittent fasting + high-quality diet | Autophagy, nutrient sensing, low basal inflammation | ``` --- ## Aging Hallmarks - What Helps ``` | Aging Hallmark | What Helps Most | Evidence Strength | | ------------------------------------| ----------------------------------------------------------------------- | --------------------------------------------------- | | Genomic instability | Sleep, exercise, antioxidants, NAD⁺ support (NR/NMN), avoiding toxins | 🟢 Strong (human + animal) | | Telomere attrition | Exercise, stress reduction, anti-inflammatory diet, avoiding smoking | 🟢 Strong (lifestyle) 🔵 Experimental (supplements) | | Epigenetic alterations | Intermittent fasting, sleep rhythm, exercise, polyphenols (resveratrol) | 🟢 Strong | | Loss of proteostasis | Exercise, fasting, heat/cold exposure, spermidine | 🟢 Strong | | Deregulated nutrient sensing | Calorie control, fasting, exercise, low sugar | 🟢 Very strong | | Mitochondrial dysfunction | Exercise, fasting, CoQ10, PQQ, NAD⁺ support | 🟢 Strong | | Cellular senescence | Exercise, fasting, senolytics (quercetin, fisetin) | 🔵 Moderate (human), 🟢 strong (animals) | | Stem cell exhaustion | Exercise, inflammation control, sleep, metabolic health | 🟢 Strong | | Altered intercellular communication | Anti-inflammatory diet, omega-3s, senolytics | 🟢 Strong | | Disabled macroautophagy | Fasting, exercise, spermidine | 🟢 Very strong | | Chronic inflammation | Diet, movement, sleep, omega-3s, stress reduction | 🟢 Very strong | | Dysbiosis | Fiber, fermented foods, plant diversity | 🟢 Strong | ``` --- ## Hallmarks of Aging - Detailed Breakdown ### 1. Genomic instability – DNA damage over time Causes: Radiation, toxins, oxidative stress, replication errors Prevention/Support: - Antioxidants (e.g., vitamin C, polyphenols) to reduce oxidative stress - DNA repair support (NAD⁺ boosters like NMN, NR) - Avoiding excessive UV and environmental toxins - Healthy lifestyle (exercise, sleep) to support repair mechanisms ### 2. Telomere attrition – Shortening of chromosome ends Causes: Cell division, oxidative stress Prevention/Support: - Telomerase-activating compounds (TA-65, Astragalus extracts) - Antioxidants and anti-inflammatory diet - Regular exercise and stress reduction - Avoid smoking and chronic infections ### 3. Epigenetic alterations – Changes in gene expression Causes: Aging, toxins, stress, poor diet Prevention/Support: - Caloric restriction or intermittent fasting (modulates epigenetic enzymes) - Polyphenols (Resveratrol, EGCG) - Healthy sleep and circadian rhythm maintenance - Certain supplements affecting methylation (B vitamins, betaine) ### 4. Loss of proteostasis – Misfolded or damaged proteins Causes: Aging, oxidative stress, cellular damage Prevention/Support: - Heat shock protein support (exercise, sauna, mild hormesis) - Autophagy induction (fasting, exercise, spermidine) - Proteasome and chaperone-supporting nutrients (curcumin, quercetin) ### 5. Deregulated nutrient sensing – Insulin, mTOR, AMPK pathways Causes: Overnutrition, sedentary lifestyle Prevention/Support: - Intermittent fasting or caloric restriction - Exercise (activates AMPK) - Compounds modulating mTOR (rapamycin in research, spermidine, resveratrol) - Balanced diet with low sugar and healthy fats ### 6. Mitochondrial dysfunction – Energy factories losing efficiency Causes: DNA damage, oxidative stress, aging Prevention/Support: - Exercise (boosts mitochondrial biogenesis) - NAD⁺ boosters (NMN, NR) - Antioxidants targeting mitochondria (CoQ10, PQQ) - Healthy diet and intermittent fasting ### 7. Cellular senescence – "Zombie" cells Causes: DNA damage, stress, telomere shortening Prevention/Support: - Senolytics (Quercetin, Fisetin, Dasatinib in research) - Exercise and calorie restriction - Anti-inflammatory diet to reduce SASP effects - Support for DNA repair and telomeres ### 8. Stem cell exhaustion – Loss of regenerative capacity Causes: Aging, inflammation, niche deterioration Prevention/Support: - Exercise and physical activity (stimulates stem cell niches) - NAD⁺ boosters - Senolytics to clear inhibitory signals - Avoid chronic inflammation and oxidative stress ### 9. Altered intercellular communication – Inflammatory signals and signaling dysregulation Causes: Chronic inflammation, SASP, aging Prevention/Support: - Anti-inflammatory diet (omega-3s, polyphenols) - Senolytics to reduce SASP - Exercise, stress reduction - Maintaining a healthy microbiome ### 10. Disabled macroautophagy – Reduced cellular cleanup Causes: Aging, nutrient excess, stress Prevention/Support: - Intermittent fasting or caloric restriction - Exercise (activates autophagy pathways) - Spermidine supplementation - Compounds like resveratrol or metformin (in research) ### 11. Chronic inflammation ("inflammaging") Causes: Persistent immune activation, senescent cells, poor lifestyle Prevention/Support: - Anti-inflammatory diet (Mediterranean diet, omega-3s, polyphenols) - Senolytics to remove pro-inflammatory cells - Stress management and sleep hygiene - Avoid smoking and pollutants ### 12. Dysbiosis – Gut microbiome imbalance Causes: Poor diet, antibiotics, aging Prevention/Support: - Probiotics and fermented foods - Prebiotic fibers (inulin, resistant starch) - Avoid chronic antibiotic overuse - Balanced diet with diverse plant foods