Longevity Supplements Stack 2025 Update: The 20 Most Impactful, Low-Risk Supplements
Disclaimer: The content of this article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical consultation, diagnosis, or treatment. Always seek the guidance of a qualified healthcare provider with any questions you may have about your health or before starting any new health regimen. Never disregard professional medical advice or delay seeking it based on information provided here.
Summary: Biohacking is the DIY approach to achieving optimal health through strategic habit changes, the combination of lifestyle choices, supplementation and medical treatments. While lifestyle is the main driver, 10% of this may be achieved through supplements. Focusing on the ones with a high cost/benefit and attractive risk/benefit is the most effective way to achieve your desired results. There are 3 supplements that I think are no-brainers for extending healthspan: liposomal curcumin, omega-3 from algae, and vitamin d3/k2 in liquid form. Next, there are 7 stellar supplements I highly recommend, 5 excellent ones, and 5 very good ones. A key shift from my 2022 perspective is my current focus on avoiding full suppression of oxidative stress, inflammation and SASPs secreted by senescent cells due to their useful signalling functions.
Introduction
I’ve started my longevity journey in 2017, and since then, I’ve constantly learned more. Much of my research has been driven by my quest for telomere extension, as described in my other article, leading to a world record of extending telomere length by 60%. This blog post is for my friends (aged 20–50) who frequently ask me what supplements I recommend.
A few words of caution here: Supplements are not a silver-bullet and can bring you from 80% to 90% (with the last 10% being more experimental and expensive treatments like stem cell injections). Being in shape (as in a BMI below 25), a healthy diet (no processed-foods, no sugar, no tab water), regular exercise and 8 hours of sleep per day set the 80/20 foundation for your longevity journey.
Here are images of my supplements. The first shows them labelled. The second is an image of the 50 supplements I take in one day.
Methodology for Supplement Selection
Conceptually, I find it useful to look at supplements from two angles: A cost/benefit analysis and a risk/benefit analysis.
In this article, I’ll recommend the 20 supplements that I believe have the highest cost/benefit analysis, ranked into 3 groups: No-Brainer, Excellent and Very Good in terms of cost/benefit. Personally, I take c. 50 supplements a day, meaning a lot of things don’t make this cut. The top 20 here provide a good starting point for anyone looking to get into supplements.
With regards to the risk/benefit analysis, I’ve decided to only include supplements in this article that have a low to non-existent risk. Therefore, they would all have an excellent risk/benefit ratio. I don’t feel comfortable publicly recommending supplements that have a questionable risk, due to lack of long-term studies and plausible hypotheses why they could cause harm (albeit most harm can, from my point of view, be mitigated by cycling).
For example, there is some evidence that supplementation of Human Growth Hormone (HGH) could aid regeneration of the Thymus, a human organ responsible for the body’s immuno-defense and which disappears with age. However, long-term HGH supplementation would likely cause cancer through putting cell growth into over-drive through the mTOR pathway.
Mainly, since 2022 my view has shifted away from the notion to fully suppress oxidative stress, inflammation and senescence-associated secretory phenotypes (SASP) secreted by sensescent cells, due to their (potentially known and unknown) useful signalling functions.
This is in opposition to the historically commonplace belief that anti-oxidants are protective. This idea has been challenged by research in recent years and progressively fallen out of fashion. Oxidative stress has long been treated as an enemy, implicated in aging, cancer, and chronic disease. But oxidative signals are also crucial messengers. Mild levels of oxidative stress can activate beneficial pathways such as autophagy (cellular clean-up) and hormesis (adaptive resilience to stress). Suppressing oxidative signals too aggressively risks disabling these essential maintenance systems, potentially making cells weaker, not stronger. To this end, suppression of oxidative stress (by free-radical scavenging antioxidants) will nullify the longevity benefits of exercise. Studies have shown that supplementation with radical-scavenging supplements like vitamins C and E inhibits the reactive oxygen species (ROS) which triggers the release of Nrf2, which would up-dial the body’s endogenous anti-oxidant defenses. This would also turn off hormesis, the process of the body to adapt and get stronger from stress.
Inflammation, often targeted by pharmaceuticals and wellness strategies, is another process with a double function. Acute inflammation is crucial for clearing infections, healing wounds, and triggering tissue regeneration. Only when inflammation becomes chronic and unresolved does it drive negative long-term outcomes. By appreciating the context and dynamics of inflammatory responses, we can intervene more precisely — supporting the resolution of inflammation rather than merely suppressing it.
Senescent cells — aged cells that stop dividing but remain metabolically active — secrete SASP factors, a cocktail of cytokines, growth factors, and proteases. While SASP has been associated with chronic inflammation and age-related decline, it also plays vital roles in wound healing, tissue remodeling, and recruiting immune responses to clear damaged cells. Total elimination of SASP risks losing these positive regenerative signals. A more nuanced approach would aim to modulate SASP activity, preserving its beneficial effects while limiting its contribution to chronic dysfunction.
Biological systems thrive on dynamic balance rather than rigid control. Trying to flatten all stress signals to zero might offer short-term relief, but in the long run, it can create a fragile system poorly equipped to adapt to new challenges.
In my risk assessment, any supplement with ROS scavenging-properties, anti-inflammatory properties are senescence-clearing properties must show strong co-benefits to make the list. Many of the supplements from my 2022 list are hence removed. Of course, in case you are sick, suffer from high inflammation, or have an abundance of senescent cells, a different temporary regime is warranted.
A couple final words: The quality of supplements matters. You want to look out for the keywords lab-tested and GMP manufactured. Also dosage and timing matters. I’ll share my regimen in the summary table below. Dosage is body weight dependent, so if you weigh much more vs. me, you should likely try a higher dose and vice versa.
Summary Table
Below, you can see a table with the top 20 supplements recommended by me with further recommendations on dosage and time of the day.
In practice, I split supplements into 3 batches, taking the first one in the morning upon waking up, the second one at lunch time with a meal, and the last one in the evening before bed time.
For each of the supplements, I explain both their mode of action with regards to longevity pathways as well as potential co-benefits of each supplement unrelated to longevity:
🧠= cognition
🌛= sleep
💪= workout performance
🦴= bone & joint health
❤️= vascular health
🧴= skin health
💦= liver detox
⚖️= hormonal health
🌱= cancer prevention
*Very high dose, going beyond typical recommendations.
Taken together, these supplements target the vast majority of the hallmarks of aging. Among the covered pathways are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, inflammation, oxidative stress, and tissue glycation. It also addresses broader aging mechanisms such as immune aging, sleep regulation, stress, detoxification, cognitive aging, and even calcification.
I will now dive into the specifics of each of the supplements I recommended. I first explain the three no-brainer supplements. I would recommend anyone to take these, regardless of your specific goals, these supplements will help enhance your health significantly. Next, I dive into the properties and benefits of seven stellar supplements, which I also highly recommend if you have the desire to expand your supplement routine. Following this, I present five excellent supplements. If you are aiming high in your biohacking journey, then these are definitely worth exploring. Finally, I present five very good supplements which can help boost and round up an already solid supplement routine. The criteria I use to class supplements is in terms of risk/benefit and cost/benefit ratio. The best supplements are those with the highest ratio: huge potential benefits with little risks and cost.
No-Brainer Supplements
Liposomal Curcumin:
Liposomal Curcumin is a cutting-edge supplement that encapsulates curcumin, the active ingredient in turmeric, within liposomes to enhance its bioavailability and therapeutic potential. This innovative delivery system shields curcumin from the harsh environment of the stomach, ensuring that a significantly higher concentration reaches the bloodstream and target cells.
According to clinical studies, Liposomal Curcumin is absorbed 8 times more effectively than standard curcumin, making it 160 times more potent than turmeric alone. This superior absorption translates into more effective anti-inflammatory, antioxidant, epigenetic and antitumor properties, as curcumin modulates various intracellular mechanisms.
For example, Curcumin is a powerful inhibitor of NF-κB, a key regulator of inflammatory responses. By suppressing NF-κB signaling, curcumin helps reduce systemic inflammation associated with numerous chronic diseases, including cardiovascular disease, diabetes, and neurodegenerative conditions. This anti-inflammatory action makes curcumin particularly effective in managing arthritis and other inflammatory disorders.
Curcumin also activates the Nrf2 pathway, a master regulator of the body’s endogenous antioxidant defenses. This activation enhances cellular resilience against oxidative damage caused by ROS, which are implicated in aging and various diseases. By modulating both inflammatory and oxidative processes, curcumin promotes overall cellular health and longevity.
One of curcumin’s most significant attributes is its anti-cancer potential. It activates the tumor suppressor protein p53, inducing apoptosis (programmed cell death) in cancer cells while inhibiting angiogenesis — the formation of new blood vessels that feed tumors. Curcumin regulates multiple cell-signaling pathways involved in cell proliferation and survival. Furthermore, curcumin has been shown to suppress telomerase activity in cancer cells, preventing their uncontrolled replication while simultaneously protecting healthy cells from oxidative stress. This dual action on telomeres contributes to curcumin’s potential in cancer management and overall cellular health.
Moreover, Curcumin offers neuroprotective benefits by reducing oxidative stress in neural tissues and inhibiting amyloid-beta plaque aggregation, which is implicated in Alzheimer’s disease. It supports mitochondrial function and activates the Nrf2 pathway in brain cells, enhancing their resilience against neurodegenerative processes. These effects may help prevent or slow the progression of conditions like Alzheimer’s, Parkinson’s, and other age-related cognitive declines.
In cardiovascular health, curcumin improves endothelial function by enhancing nitric oxide production and reducing oxidative damage to blood vessels. Its anti-inflammatory properties further help lower blood pressure and reduce the risk of atherosclerosis. Additionally, curcumin’s ability to inhibit lipid peroxidation protects cellular membranes from oxidative stress, contributing to overall cardiovascular protection.
Curcumin plays a role in slowing epigenetic aging by influencing histone methylation and DNA repair processes, potentially reversing age-related gene silencing. It also acts as a DHT (dihydrotestosterone) inhibitor, which may help reduce hair loss and support prostate health.
Additionally, curcumin blocks iron absorption, which can be beneficial for individuals with iron overload conditions or those seeking to reduce oxidative stress caused by excess iron. It also enhances glutathione synthesis — a critical antioxidant that detoxifies harmful substances and protects cells from damage. Another key benefit of curcumin is its ability to boost serotonin levels, contributing to improved mood and mental health.
Despite its broad-spectrum advantages, curcumin should be used cautiously by individuals on anticoagulants or with bleeding disorders due to its mild blood-thinning properties. It may interact with certain medications, and cycling curcumin supplementation may mitigate potential long-term risks associated with its potent bioactivity.
In conclusion, liposomal curcumin represents an advanced delivery system that maximizes the therapeutic potential of this remarkable compound across diverse health domains. Its broad-spectrum benefits make it a cornerstone supplement for longevity and disease prevention, addressing multiple pathways involved in the aging process and chronic disease development.
Omega-3 from Algae
Omega-3 fatty acids derived from algae, particularly DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), offer a wide range of health benefits with excellent safety and sustainability profiles. Unlike fish oil, algae-based Omega-3 is vegan-friendly and avoids the risk of heavy metal contamination often associated with marine sources. These fatty acids are essential for maintaining cardiovascular health, supporting brain function, and reducing inflammation throughout the body.
One of the standout benefits of Omega-3 is its potent anti-inflammatory properties. EPA and DHA can directly inhibit inflammasomes, molecular complexes that trigger the release of inflammatory cytokines. This mechanism makes Omega-3 effective in reducing chronic inflammation, which is a key contributor to many age-related diseases such as cardiovascular disease, neurodegenerative disorders like Alzheimer’s, and autoimmune conditions. Additionally, Omega-3 fatty acids suppress NF-kappaB signaling, the pathway heavily involved in inflammation and aging processes, while activating beneficial pathways like Nrf2 to enhance antioxidant defenses.
In terms of brain health, DHA plays a critical role in maintaining neuronal structure and function. It has been shown to boost levels of brain-derived neurotrophic factor (BDNF), which supports neurogenesis and synaptic plasticity. This makes Omega-3 particularly valuable for cognitive function, memory retention, and protection against neurodegenerative diseases. Furthermore, higher blood levels of Omega-3 have been associated with slower telomere shortening over time, suggesting its potential role in promoting longevity.
Omega-3 also supports cardiovascular health by improving lipid profiles — reducing triglycerides and increasing HDL cholesterol — and decreasing blood pressure. Its ability to modulate endothelial function and reduce arterial stiffness further contributes to heart health. Additionally, DHA and EPA have been linked to improved mood regulation and reduced symptoms of depression due to their impact on neurotransmitter pathways.
Overall, algae-derived Omega-3 is a versatile supplement with robust evidence supporting its benefits for inflammation reduction, brain health, cardiovascular protection, and longevity.
Vitamin D3/K2 in liquid form
Vitamin D3 and K2 are essential nutrients that work synergistically to support bone health, cardiovascular function, and immune resilience. Many people in Europe are deficient in Vitamin D, especially during winter months, with studies showing that up to 30% of adults and 80% of institutionalized elderly individuals have insufficient levels. This widespread deficiency highlights the importance of supplementation, particularly when paired with Vitamin K2 to maximize benefits.
Vitamin D3 enhances calcium absorption from the diet, while Vitamin K2 ensures calcium is directed to bones and teeth rather than accumulating in soft tissues like arteries. This combination prevents arterial calcification and supports strong bone mineral density (BMD), reducing the risk of osteoporosis and fractures. Research demonstrates that supplementing both nutrients together is more effective at improving BMD and preventing bone loss than taking either alone.
Beyond skeletal benefits, Vitamin D3/K2 contributes to cardiovascular health by reducing arterial stiffness and protecting against calcification-related heart disease. Vitamin D3 also plays a role in regulating blood pressure and supporting immune function, while K2 helps lower inflammation and improve metabolic health. Together, these vitamins promote optimal calcium metabolism, ensuring it strengthens bones without harming arteries.
Vitamin D deficiency has been strongly associated with worse outcomes in COVID-19 infections, highlighting its critical role in immune modulation. Studies have shown that individuals with low levels are at a significantly higher risk of severe disease progression, including increased rates of hospitalization, ICU admission, and mortality. Vitamin D helps regulate the immune system by suppressing pro-inflammatory cytokines. Supplementation has been associated with reduced infection rates and lower mortality, particularly among individuals with pre-existing deficiencies.
Beyond its implications for COVID-19, vitamin D deficiency is linked to a range of other health issues. It is associated with weakened immune function, increasing susceptibility to infections, and chronic inflammation, which contributes to diseases such as diabetes, cardiovascular disorders, and autoimmune conditions. Furthermore, low vitamin D levels are connected to mood disorders like depression and cognitive decline in aging populations.
The liquid form of this supplement offers superior bioavailability, allowing for efficient absorption and flexible dosing. This format is particularly beneficial for individuals with limited sun exposure or dietary intake of these vitamins. By addressing deficiencies common in Europe (or any place with low sunlight exposure), regular use of liquid Vitamin D3/K2 can support long-term health by improving bone density, reducing cardiovascular risks, enhancing immunity, and promoting overall well-being.
Stellar Supplements
L-Taurine
L-Taurine is a sulfur-containing amino acid that plays a multifaceted role in supporting cellular health and longevity. It is a potent antioxidant that stabilizes cell membranes and protects against oxidative damage in tissues such as the heart, eyes, and brain. L-Taurine also regulates calcium levels within cells and modulates inflammation, indirectly reducing oxidative stress. Its safety profile is excellent, making it suitable for daily supplementation without cycling.
The benefits of L-Taurine span across various domains of health. It has cardioprotective effects, helping to lower blood pressure and reduce the risk of cardiovascular diseases. Additionally, it supports fat oxidation and athletic performance, making it popular among fitness enthusiasts. L-Taurine also exhibits neuroprotective properties by increasing GABA levels and lowering cortisol, which can improve mood and reduce stress. Its ability to reduce acetaldehyde levels after alcohol intake further underscores its detoxifying capabilities. However, caution is advised when combining L-Taurine with caffeine, as this may amplify certain physiological effects.
From a longevity perspective, L-Taurine has shown remarkable potential in extending lifespan in animal studies. Research indicates that taurine supplementation can drive up the expression of the p53 tumor suppressor protein, which plays a critical role in DNA repair and apoptosis of damaged cells. This mechanism may contribute to its anti-aging effects by promoting cellular health and reducing cancer risks. Studies on animals have demonstrated significant lifespan extension linked to taurine supplementation, suggesting its promise as a longevity-enhancing intervention.
In summary, L-Taurine is a versatile supplement with broad-spectrum benefits for cardiovascular health, stress reduction, athletic performance, and cellular protection. Its role in life extension, particularly through mechanisms like p53 activation, makes it an exciting candidate for those interested in promoting longevity while maintaining overall health.
Calcium Alpha Ketoglutarate (Ca-AKG)
Calcium Alpha-Ketoglutarate (Ca-AKG) is a mitochondrial fuel and epigenetic modulator with broad-spectrum longevity benefits. It mimics caloric restriction’s effects by activating AMPK, a key metabolic regulator linked to lifespan extension. This activation inhibits mTOR, a driver of aging, while promoting mitochondrial biogenesis and reducing oxidative stress through enhanced electron transport chain efficiency. Studies in mice show Ca-AKG drastically increases healthspan and reduces epigenetic age, suggesting systemic rejuvenation potential.
Ca-AKG’s standout feature lies in its ability to modulate DNA and histone demethylation, processes critical for maintaining youthful gene expression of the epigenome. By influencing epigenetic marks, it repairs age-related epigenetic drift and preserves stem cell health — a cornerstone of tissue regeneration. Preclinical research highlights its role in reducing ROS formation and enhancing autophagy, which clears cellular debris and delays senescence. These effects mirror caloric restriction, positioning Ca-AKG as a potent epigenetic rejuvenator. It also intersects with other key anti-aging pathways: activating AMPK/SIRT1 (central to energy regulation and cellular repair), suppressing NF-κB-driven inflammation, and supporting redox homeostasis.
Beyond longevity, Ca-AKG supports muscle recovery, kidney/liver function, and fat metabolism while maintaining a high safety profile. It acts as a mitochondrial fuel, boosting ATP production and mitigating age-related metabolic decline. Emerging evidence suggests it may slow hair loss and reduce heavy metal toxicity (e.g., lead absorption). Its mTOR inhibition also aligns with cancer prevention strategies, as unchecked mTOR activity drives tumor growth.
By mimicking fasting-induced stress responses, it triggers hormesis — a low-dose stress that upregulates cellular repair mechanisms. While human trials are pending, its dual role in epigenetic regulation and mitochondrial health makes it a compelling candidate for life-extension stacks.
Glucosamine sulfate
Glucosamine sulfate is a versatile supplement best known for its ability to support joint health and cartilage repair. By delaying the breakdown of cartilage and enhancing collagen production, it improves joint functionality and reduces inflammation. These benefits extend to skin health, as the supplement promotes collagen synthesis, reducing wrinkles and improving overall skin texture. Glucosamine sulfate also acts as a precursor to hyaluronic acid, which supports skin hydration and elasticity, making it a valuable addition to anti-aging regimens.
What sets glucosamine sulfate apart is its profound impact on longevity and mortality risk reduction. Research suggests that regular use of glucosamine is associated with a significantly lower risk of death from major causes such as cardiovascular disease, cancer, respiratory diseases, and digestive disorders. These protective effects are thought to stem from its ability to mimic caloric restriction — a proven longevity intervention — by impairing glucose metabolism and activating AMPK. This activation enhances mitochondrial biogenesis and cellular resilience, promoting overall metabolic health. Additionally, glucosamine induces mild oxidative stress in mitochondria, triggering hormetic responses that strengthen cellular defenses without suppressing beneficial ROS.
Glucosamine sulfate may also act similarly to metformin, a widely studied anti-aging drug. By inhibiting the mTOR pathway — a key regulator of growth and aging — it potentially slows tumor growth while promoting autophagy, the cellular cleanup process vital for longevity. Its nuanced modulation of oxidative stress further highlights its role in promoting healthspan without interfering with essential cellular signaling processes.
The supplement’s ability to lower all-cause mortality risk has been compared to the benefits of regular exercise, underscoring its systemic health advantages. Its safety profile is excellent when taken at recommended doses, making it a low-risk yet high-reward addition to any longevity-focused supplement stack. Glucosamine sulfate not only supports joint and skin health but also contributes significantly to extending lifespan and improving quality of life.
L-Carnosine
L-Carnosine is a dipeptide composed of beta-alanine and histidine, offering a wide range of benefits for longevity and cellular health. One of its most remarkable properties is its ability to inhibit the formation of advanced glycation end-products (AGEs), which are harmful compounds formed when proteins or fats combine with sugars. AGEs contribute to aging and chronic diseases such as diabetes, cardiovascular issues, and neurodegenerative conditions. By blocking glycation and repairing glycinated tissues, L-Carnosine helps preserve skin elasticity, eye lens clarity, and overall cellular integrity.
A standout feature of L-Carnosine is its potential to delay or reverse cellular senescence. It has been shown to extend the replicative lifespan of human cells by reducing telomere damage and slowing telomere shortening rates. This mechanism promotes a more youthful cellular phenotype and increases population doublings in cultured cells, making it a promising anti-aging supplement. Additionally, L-Carnosine may stimulate telomerase activity, further supporting telomere maintenance and cellular rejuvenation.
L-Carnosine also offers neuroprotective benefits by reducing brain damage associated with beta-amyloid accumulation — a hallmark of Alzheimer’s disease — and protecting neurons from zinc- and copper-mediated toxicity. It may improve cognitive function by increasing neurotransmitter levels in the brain while also acting as an anti-convulsant. Beyond this, its ability to chelate heavy metals like copper and zinc adds another layer of protection against oxidative stress and neurodegeneration.
On a broader scale, L-Carnosine supports digestive health by promoting healing in conditions such as stomach ulcers. It also helps prevent arterial plaque buildup, contributing to cardiovascular health. For physical performance, it acts as a pH buffer in muscles, reducing lactic acid buildup during exercise and enhancing endurance. Its ability to maintain ATP stores under stress further highlights its role in energy metabolism and recovery.
With an excellent safety profile, L-Carnosine stands out as a versatile supplement for promoting longevity. Its ability to address multiple aging mechanisms — from telomere protection to glycation inhibition — makes it a cornerstone of any anti-aging regimen.
Creatine
Creatine is a widely studied supplement renowned for its ability to boost physical performance, but its benefits extend far beyond the gym. It plays a vital role in energy production by replenishing ATP, the body’s primary energy source, and supports both muscle and brain function. Many people, particularly vegetarians and vegans, are deficient in creatine because it is naturally found in animal-based foods, making supplementation an non-negotiable option for addressing this gap.
In general, creatine is best known for its ability to increase strength and muscle growth by enhancing energy availability during exercise. It also supports mental resilience under stress, helping maintain cognitive function during high-pressure situations or lack of sleep. This makes it a versatile supplement for both physical and mental optimization.
Recent research highlights creatine’s ability to improve memory, focus, and mental processing speed. Studies show that supplementation enhances brain energy reserves, supports neurotransmitter production, and improves synaptic function. These effects are especially pronounced in individuals with low dietary creatine intake or during periods of mental fatigue, such as sleep deprivation.
Furthermore, creatine has shown promise in protecting against age-related cognitive decline and oxidative stress. It helps preserve brain health by improving hippocampal plasticity and reducing damage caused by aging processes, making it potentially beneficial for long-term brain health.
Beyond its effects on performance and cognition, creatine may support heart health by improving energy metabolism in cardiac cells. Additionally, it has been linked to better glucose tolerance and reduced inflammation, suggesting broader health applications.
Creatine is a safe and affordable supplement with wide-ranging benefits for physical performance, brain health, and overall well-being. Its ability to address dietary deficiencies, particularly in vegetarians, while enhancing both physical and cognitive resilience makes it an essential addition to any longevity-focused regimen.
EGCG (Epigallocatechin gallate)
EGCG, the primary catechin in green tea, is a potent compound with wide-ranging benefits for longevity and health. It activates the NRF2 pathway, which regulates antioxidant and detoxification genes, providing protection against oxidative stress while preserving beneficial ROS signaling. Unlike direct radical scavengers, EGCG enhances endogenous antioxidant defenses without suppressing hormesis, ensuring exercise benefits are maintained. Additionally, EGCG chelates metal ions and inhibits pro-oxidant enzymes, making it a versatile antioxidant with strong protective effects against lipid peroxidation and cellular damage.
EGCG also exhibits anti-inflammatory properties, primarily through inhibition of NF-κB, the key driver of chronic inflammation linked to aging and diseases such as cardiovascular disease, cancer, and neurodegeneration. By suppressing pro-inflammatory cytokines like interleukin-6 (IL-6) and TNF-α, EGCG reduces systemic inflammation and mitigates the harmful effects of SASP, which is secreted by aged cells. This anti-inflammatory action complements its antioxidant effects to promote cellular health.
On an epigenetic level, EGCG inhibits DNA methyltransferases (DNMTs), reversing hypermethylation that silences tumor suppressor genes such as p53. This demethylating effect restores protective gene expression and counters age-related epigenetic drift. EGCG also modulates histone acetylation via SIRT1 activation, enhancing DNA repair and telomere stability. These mechanisms not only prevent cancer but also slow age-dependent telomere shortening.
For metabolic health and longevity, EGCG mimics caloric restriction by activating AMPK and promoting autophagy, processes linked to reduced age-related disease risk. It supports cardiovascular health by lowering LDL oxidation and blood pressure while improving insulin sensitivity. Its mTOR inhibition further aligns with longevity strategies that prioritize intermittent metabolic regulation. However, doses exceeding 800mg/day may pose liver risks, necessitating careful dosing.
Black Garlic
Garlic, particularly in its aged or black form, is a powerful supplement with a wide range of health benefits. Its active compounds, such as allicin and S-allyl cysteine, exhibit strong antioxidant and anti-inflammatory properties. These compounds help neutralize excess radicals, reduce lipid peroxidation, and enhance the activity of endogenous antioxidant enzymes. Garlic also supports cardiovascular health by lowering blood pressure, improving cholesterol profiles, and reducing oxidative stress and inflammation. Additionally, it has antimicrobial properties that combat bacterial resistance and infections, making it a versatile tool for immune support.
One of garlic’s most intriguing benefits lies in its epigenetic effects. It may slow harmful epigenetic methylation processes associated with aging and cancer development, offering genomic protection. By modulating gene expression through these pathways, garlic contributes to long-term health and resilience against age-related diseases.
Garlic also has neuroprotective effects. It helps regulate neurotransmitter levels, potentially improving mood and reducing the risk of neurodegenerative diseases like Alzheimer’s. Its ability to inhibit NF-kappaB signaling further reduces chronic inflammation — a key driver of neurodegeneration. Additionally, garlic may positively influence gut microbiota by decreasing trimethylamine (TMA) production, which is linked to cardiovascular disease when converted into TMAO.
Overall, garlic’s combination of antioxidant, anti-inflammatory, epigenetic, and antimicrobial properties makes it a cornerstone supplement for longevity and health optimization. With an excellent safety profile when consumed in appropriate doses, it is an effective addition to any regimen aimed at reducing oxidative stress, supporting cardiovascular health, and enhancing overall vitality.
Excellent Supplements
Spermidine
Spermidine is a polyamine that plays a key role in cellular health and longevity by promoting autophagy, the process of clearing damaged proteins and organelles to maintain cellular function. This mechanism reduces oxidative stress, preserves mitochondrial integrity, and protects DNA from damage, which are critical factors in slowing aging.
Spermidine has been associated with telomere protection and even potential lengthening, making it a valuable tool for combating age-related decline. It also modulates the SASP, reducing inflammatory signaling while preserving beneficial cellular functions. Studies suggest spermidine may prevent liver fibrosis, improve memory by dissolving amyloid-beta plaques, and enhance cardiovascular health through improved endothelial function.
In addition to its anti-inflammatory and anti-aging properties, spermidine has shown promise in extending lifespan in animal models and maintaining cognitive function during aging. However, high doses could increase stroke risk due to its vasoactive effects, emphasizing the importance of careful dosing. Its senomorphic properties — modulating rather than eliminating senescent cells — make it an innovative approach to longevity interventions. While human trials are still ongoing, spermidine’s safety profile appears favorable at recommended dosages.
Pyrroloquinoline Quinone (PQQ)
PQQ is a potent antioxidant which main unique function is the stimulation of mitochondrial biogenesis by activating PGC-1α, enhancing energy metabolism and cellular resilience. It supports mitochondrial health by reducing oxidative stress through NRF2 pathway activation and scavenging ROS. These mechanisms make PQQ particularly beneficial for tissues with high energy demands, such as the brain and heart. Studies have shown that PQQ improves cognitive flexibility in younger adults and enhances memory retention in older populations by increasing cerebral blood flow.
Beyond its mitochondrial benefits, PQQ has been linked to improved sleep quality and lower systemic inflammation through reductions in markers like C-reactive protein (CRP) and IL-6. Its ability to drive mitochondrial biogenesis positions it as a valuable supplement for combating age-related declines in energy production and cellular function. With rapid metabolism minimizing toxicity risks, PQQ offers broad-spectrum benefits for longevity and healthspan optimization.
Pycnogenol
Pycnogenol, extracted from French maritime pine bark, is a powerful antioxidant rich in procyanidins. It protects cells by neutralizing free radicals and activating the NRF2 pathway, which boosts the body’s natural antioxidant defenses. Pycnogenol also supports vascular health by improving nitric oxide production and reducing oxidative stress in blood vessels, helping to prevent conditions like stroke, heart disease, varicose veins, and hypertension.
Beyond cardiovascular benefits, Pycnogenol contributes to healthy aging in multiple ways. It enhances skin elasticity and hydration, reduces signs of aging such as wrinkles and pigmentation, and offers photoprotection against UV-induced skin damage. In the brain, it improves cerebral blood flow, which supports better attention, memory, executive function, and mood. Pycnogenol has also been shown to enhance athletic endurance and male fertility. Clinical studies report reductions in key inflammatory markers, such as CRP and IL-6, highlighting its powerful systemic anti-inflammatory effects.
Lycopene
Lycopene is a carotenoid found in tomatoes that acts as a potent antioxidant and protecting cell membranes from lipid peroxidation. Its primary benefits include cardiovascular protection through improved endothelial function and reduced LDL oxidation.
Lycopene has also been linked to prostate health by lowering the risk of prostate cancer while acting as a natural sunscreen due to its ability to absorb UV radiation at the skin level. Its fat-soluble nature allows it to be stored in tissues for prolonged activity.
L-Theanine
L-Theanine is an amino acid primarily found in green tea that promotes relaxation without causing drowsiness by modulating alpha brain waves associated with calm focus. It enhances neurotransmitter balance by increasing GABA levels while reducing excitatory signals from glutamate.
L-Theanine also exhibits mild antioxidant properties that support brain health by reducing oxidative stress within neural tissues. When combined with caffeine or EGCG from green tea extract, it synergistically enhances cognitive performance while mitigating caffeine-induced jitters.
Very Good Supplements
Ubiquinol
Ubiquinol is the active form of Coenzyme Q10 (CoQ10) and serves as a powerful antioxidant within mitochondrial membranes. It supports ATP production, which is essential for energy-intensive tissues like the heart and brain. Ubiquinol enhances brain health by improving cerebral blood flow, protecting neurons from oxidative damage, and supporting synaptic plasticity. Clinical studies have demonstrated improved memory and executive function in older adults after supplementation. Additionally, ubiquinol has neuroprotective benefits that may mitigate brain injury.
Ubiquinol plays a vital role in keeping our cells energized and healthy. It acts as a key carrier in the electron transport chain, helping mitochondria produce ATP — the energy that powers all cellular functions. As we age, protecting our cells from oxidative damage becomes critical, especially in the mitochondria, where most energy production happens. Damage here can impair energy production and speed up aging. Ubiquinol also protects LDL cholesterol from oxidation, which is an early step in the formation of arterial plaque. By shielding mitochondrial DNA, proteins, and LDL cholesterol from free radicals, Ubiquinol helps maintain cellular health and supports both longevity and cardiovascular protection.
This supplement also plays a role in insulin sensitivity by activating AMPK pathways, which enhance glucose uptake in muscle cells. It protects against cardiovascular issues by reducing LDL oxidation and replenishing CoQ10 levels depleted by statins. With a long half-life ensuring sustained activity within tissues, ubiquinol is an indispensable tool for maintaining mitochondrial integrity and optimizing cellular energy production.
Magnesium citrate
Magnesium is a vital mineral involved in over 300 enzymatic reactions that regulate energy production (via ATP synthesis), muscle contraction, nerve function, DNA repair, and heart health. It plays a critical role in sleep quality by modulating neurotransmitters like GABA and serotonin, helping reduce sleep latency and improve overall sleep efficiency. Due to the wide involvement of Magnesium in physiological processes, supplementation is recommended.
In addition to its physiological benefits, magnesium supports bone density by activating osteoblasts and prevents chronic diseases such as type 2 diabetes through improved insulin sensitivity. It lowers inflammation by inhibiting NF-κB pathways while stabilizing cell membranes to protect against oxidative stress. Magnesium citrate or glycinate forms are often recommended due to their superior bioavailability.
Zinc
Zinc is an essential trace mineral critical for immune function, wound healing, DNA synthesis, and cell division. It improves insulin sensitivity. Zinc also supports reproductive health by influencing testosterone levels and sperm quality.
Its antioxidant properties help combat oxidative stress by stabilizing cell membranes while supporting endogenous antioxidant enzymes like superoxide dismutase (SOD). Zinc’s benefits extend to skin health through acne prevention via anti-inflammatory effects on sebaceous glands. However, excessive intake can lead to adverse effects such as nausea or interference with copper absorption.
L-Glycine
L-Glycine is a non-essential amino acid with diverse benefits for health and longevity. It acts as an antioxidant precursor by supporting glutathione synthesis while promoting restful sleep through its calming effects on the nervous system. Glycine also protects the liver from damage by antagonizing methionine overloads that can lead to metabolic imbalances.
Additionally, glycine enhances collagen production for skin elasticity and joint health while supporting muscle repair after exercise. Its ability to modulate inflammation further contributes to its protective effects against age-related conditions like arthritis or cardiovascular disease.
Milk Thistle
Milk thistle contains silymarin, a complex of flavonolignans with potent antioxidant properties that greatly support liver health, the stand-out feature of milk thistle. Silymarin reduces lipid peroxidation and enhances liver detoxification pathways by upregulating antioxidant enzymes like glutathione peroxidase. These actions make milk thistle particularly effective in protecting against liver damage caused by toxins or alcohol.
Beyond liver protection, milk thistle exhibits anti-inflammatory effects that contribute to overall cellular health. It may also have potential anti-cancer properties through its ability to modulate inflammatory pathways and reduce oxidative stress. Milk thistle’s safety profile is excellent when used at recommended dosages.
What’s not included (although I take them with cycling)
Several supplements that are common in longevity stacks are not included in my stack due to their unclear effect in young people and/or long-term adverse effects without cycling. Those include:
N-Acetyl L-Cysteine
N-Acetyl Cysteine (NAC) is a powerful antioxidant and precursor to glutathione, the body’s primary endogenous antioxidant. It is widely used to combat oxidative stress, support detoxification, and improve respiratory health. NAC replenishes intracellular glutathione levels, which helps neutralize reactive oxygen species (ROS) and reduce inflammation. NAC is great at reducing inflammation / acne in the skin and helping with liver detoxification.
However, long-term use of NAC without cycling may pose risks. Chronic supplementation could disrupt the body’s natural redox balance by reducing ROS levels excessively, potentially impairing hormetic stress responses that are essential for cellular adaptation and repair. As main precursor of glutathione, lots of NAC supplementation will slow down the body’s natural glutathione production.
Additionally, NAC has been associated with increased homocysteine levels, which may raise cardiovascular risk if not monitored. Furthermore, while NAC shows promise in reducing cancer risk in specific populations, there are concerns about its potential to interfere with certain cellular processes in ways that could have unintended consequences over time.
R Alpha Lipoic Acid
R Alpha Lipoic Acid (R-ALA) is one of the most potent antioxidants that neutralizes free radicals in both lipid and aqueous environments, regenerates glutathione and vitamins C/E, and activates the NRF2 pathway to upregulate endogenous antioxidants. It enhances mitochondrial function, chelates heavy metals, and improves insulin sensitivity by modulating glucose metabolism pathways. R-ALA also reduces glycation end-products (AGEs), offering protection against diabetic complications.
Chronic use may suppress natural antioxidant systems through overreliance on exogenous scavenging, blunting NRF2 activation over time. R-ALA’s metal-chelating properties could inadvertently redistribute toxic metals like mercury if detox pathways are overwhelmed. Therefore, R-ALA should be approached with some caution.
NMN Powder
Nicotinamide Mononucleotide (NMN) boosts NAD+ levels, activating sirtuins like SIRT1/SIRT3 to enhance DNA repair, mitochondrial biogenesis, and metabolic regulation. It mimics caloric restriction effects, improving insulin sensitivity and cardiovascular function. NMN also supports neuroprotection and may delay age-related NAD+ decline, which is critical for energy metabolism and genomic stability.
Uninterrupted supplementation risks NAD+ precursor feedback inhibition, potentially downregulating rate-limiting enzymes like NAMPT. Chronic elevation of NAD+ could fuel cancer cell proliferation via upregulated sirtuin activity in pre-malignant cells. Therefore, a permanent supplementation with NMN or NAD+ is not advisable.
Fisetin
Fisetin is a senolytic flavonoid that clears senescent cells by inhibiting pro-survival pathways like BCL-2 and activating apoptosis. It also activates NRF2, reducing oxidative stress and inflammation, while enhancing cognitive function via BDNF upregulation. Fisetin’s iron-chelating properties further protect against lipid peroxidation and mitochondrial dysfunction.
Continuous use may impair tissue regeneration by excessively targeting senescent cells involved in wound healing and stem cell function. Over-suppression of SASP might weaken immune surveillance against precancerous cells. Therefore, Fisetin should be cycled, I recommend using it three days per quarter in high dosage.
High-dose Resveratrol
Resveratrol activates SIRT1 and AMPK, mimicking caloric restriction to enhance mitochondrial efficiency and autophagy. It inhibits NF-κB, reducing inflammation, and upregulates NRF2 for antioxidant defense. Resveratrol also suppresses cancer initiation by modulating p53 and blocking angiogenesis. Its phytoestrogenic properties may support cardiovascular and bone health in aging populations.
Chronic SIRT1 activation may dysregulate circadian rhythms and mTOR signaling, paradoxically promoting insulin resistance. Resveratrol’s pro-oxidant effects at high doses may damage DNA in normal cells, offsetting its chemopreventive benefits. A low dose of 100mg/d of Resveratrol is probably enough to gain most of the benefits without risking adverse effects.
Conclusion
Longevity isn’t just about living longer, it’s about maximizing the quality of the years we do have. By targeting the core hallmarks of aging through thoughtful, low-risk supplementation, we can tilt the odds in favor of healthspan: more energy, sharper cognition, and fewer disease risks as we age.
The results speak for themselves. As shown in the graph below, my biological aging rate has consistently been trailing below 1.0 over the past years. Right now, for every year that passes on the calendar, my body is aging just 0.88 years, a sign of slower biological wear and tear. This may not sound dramatic, but over time, even small reductions in aging rate can add up to years of extra vitality and resilience.
I hope this article encourages you to take more mindful control over your health span. The information should help you design your own supplement strategy, grounded in evidence, mindful of risk, and optimized for real, measurable progress.
Remember that each person is a whole ecosystem — what works for me might be different from you. I encourage you to try out different things and find what’s the best supplement and habits routine that aligns with your personal goals, your priorities, and your lifestyle.
