Nutrition

Astaxanthin is a ketocarotenoid pigment produced predominantly by the microalga Haematococcus pluvialis and accumulated through the food chain in crustaceans, salmon, and trout, accounting for their characteristic pink-red coloration. Its molecular structure — a polyene chain with carbonyl and hydroxyl groups on both ionone rings — enables it to span the full width of the lipid bilayer and scavenge singlet oxygen and free radicals more potently than many other carotenoids, including β-carotene. Unlike certain antioxidants, it does not act as a pro-oxidant at high concentrations under physiological conditions. Proposed mechanisms relevant to longevity include Nrf2 activation, NF-κB inhibition, mitochondrial protection, and modulation of inflammatory cytokines. Rodent studies show improvements in oxidative stress, immune parameters, and some cardiovascular markers; human RCTs are small and generally short-term, reporting modest effects on lipid oxidation biomarkers, skin aging, exercise-induced muscle damage, and inflammation. Synthetic astaxanthin (dominant in aquaculture) and natural algal-derived forms differ in esterification and stereochemistry, which may affect bioavailability. Evidence for direct human longevity benefit remains preliminary.

Blue Zones are regions reported to have unusually many centenarians. The popularly cited list (Buettner) includes Okinawa (Japan), Sardinia (Italy), Nicoya (Costa Rica), Ikaria (Greece), and Loma Linda (USA). Shared features include plant-based diets, moderate caloric intake, low-intensity movement, strong social ties, and purpose. Saul Newman has argued that supercentenarian counts may be inflated by age-record errors, pension fraud, and missing birth registries; this methodological critique was recognised when Newman was awarded the 2024 Ig Nobel Prize in Demography for the work, and the demographic robustness of the original Blue Zone identifications is now contested.

Coenzyme Q10 (ubiquinone) is a lipid-soluble molecule essential for mitochondrial electron transport and ATP production, and an intracellular antioxidant. Endogenous levels decline with age and with statin use. Clinical evidence is strongest in heart failure: in the Q-SYMBIO trial (300 mg/day), CoQ10 reduced all-cause mortality and major cardiovascular events in chronic heart failure patients; however, replication has been inconsistent and most other trials have been smaller. Effects on blood pressure and statin-related muscle symptoms are modest; longevity benefits in healthy adults are not established.

Creatine is a guanidino compound synthesized endogenously in liver and kidney from arginine, glycine, and methionine, and obtained exogenously from red meat, fish, and supplements. As phosphocreatine, it rapidly regenerates ATP from ADP via the creatine kinase reaction during high-intensity efforts, buffering energy supply in muscle and brain. Creatine monohydrate supplementation (3–5 g/day after an optional loading phase) is one of the most extensively validated ergogenic aids, consistently increasing lean mass and strength in resistance-trained adults across meta-analyses. Emerging evidence in older adults indicates additional benefits on muscle preservation and fall prevention, with some RCTs and meta-analyses also suggesting modest cognitive effects — particularly relevant because older adults have lower dietary creatine intake and endogenous synthesis declines. Safety at habitual supplementation doses is well established in healthy adults, though those with pre-existing kidney disease should consult a physician.

Curcumin is the principal polyphenol in turmeric (Curcuma longa) and modulates NF-kB, Nrf2, and other inflammatory and oxidative pathways. Standard curcumin has very low oral bioavailability; supplements typically use piperine, phospholipid, or nanoparticle formulations. Meta-analyses suggest modest reductions in inflammatory markers, joint pain, and lipid measures, but effects vary by formulation and study quality. Evidence for direct longevity benefits in humans is limited.

EGCG is the most abundant catechin in green tea and a polyphenol with antioxidant, anti-inflammatory, and AMPK-modulating activity. Observational data link green tea consumption to lower cardiovascular and all-cause mortality. Trials of EGCG supplements show small effects on lipids, blood pressure, and body weight. High-dose extracts (typically above 800 mg EGCG/day) have been associated with liver enzyme elevations and hepatotoxicity; the European Food Safety Authority (EFSA) has identified this threshold as a safety concern and the EU has imposed limits on EGCG in food supplements. Direct evidence for human longevity from isolated EGCG remains limited.

Fisetin is a flavonoid found in strawberries, apples, and persimmons. In aged mice, Yousefzadeh et al. (2018, EBioMedicine) reported reduced senescent cell burden and extended median lifespan using a late-life intermittent dosing protocol; the paper also documented reduced age-associated tissue dysfunction. Independent replication remains limited. Mechanisms include induction of apoptosis in senescent cells and modulation of inflammatory pathways, making it a candidate dietary senolytic under investigation. Human trials are ongoing, and clinical evidence in people remains preliminary.

Glycine is the smallest and simplest amino acid, non-essential under normal conditions but conditionally essential in aging, pregnancy, and disease states where demand may exceed endogenous synthesis from serine and threonine. It is the most abundant amino acid in collagen and a structural backbone of glutathione (as the third residue of the γ-Glu-Cys-Gly tripeptide), explaining its role as a rate-limiting substrate for glutathione synthesis in older adults whose glycine levels are typically low. Glycine also acts as an inhibitory neurotransmitter in the spinal cord and brainstem, modulates NMDA receptor activity, and participates in one-carbon metabolism, bile acid conjugation, and creatine synthesis. Dietary sources include gelatin, skin, bones, and connective tissue; modern lean-meat-focused diets provide relatively little. Animal studies show lifespan extension by glycine supplementation in mice (ITP, Miller 2019); evidence from C. elegans is indirect, arising mainly from methionine restriction and one-carbon metabolism studies rather than direct glycine trials. In humans, glycine deficiency in older adults is increasingly recognized, and small pilot trials (particularly in the context of GlyNAC, n≈8 each) suggest restoration of glutathione levels and improvements in multiple aging-related biomarkers.

GlyNAC is the combined oral supplementation of glycine and N-acetylcysteine (NAC), designed to replenish both precursors of the tripeptide glutathione (γ-Glu-Cys-Gly), which declines progressively with age. The combination addresses the limiting precursors simultaneously — cysteine (via NAC) and glycine — rather than the gamma-glutamylcysteine step, which is typically less rate-limiting in older adults. Pioneered by Rajagopal Sekhar and colleagues at Baylor College of Medicine, a series of randomized, double-blind pilot trials in older adults (GlyNAC trials, published 2021–2024) using 16–24 weeks of supplementation documented restoration of erythrocyte glutathione to levels seen in young adults and improved multiple aging-associated deficits including mitochondrial fuel oxidation, oxidative stress, inflammation, endothelial dysfunction, insulin resistance, genomic damage, muscle strength, and gait speed. Evidence remains limited to short-duration trials with small samples; longer-term RCTs with clinical outcome endpoints are lacking. GlyNAC is commercially available as a dietary supplement and has no approved indication.

The Mediterranean diet is an eating pattern emphasizing vegetables, fruits, legumes, whole grains, nuts, olive oil, and fish, with moderate dairy and limited red meat. Rich in monounsaturated fats, fiber, and polyphenols, it is associated with lower systemic inflammation, improved lipid profiles, and better endothelial function. Long-term adherence is associated in cohort studies and the PREDIMED trial (which tested Mediterranean diet supplemented with extra-virgin olive oil or mixed nuts; retracted and republished in 2018) with reduced cardiovascular events, type 2 diabetes risk, and all-cause mortality.

The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) is a hybrid eating pattern targeting brain health. It emphasizes leafy greens, berries, nuts, whole grains, beans, fish, poultry, and olive oil while limiting red meat, butter, cheese, pastries, and fried food. Observational studies link higher adherence to slower cognitive decline and lower Alzheimer's incidence, though a 2023 randomized trial showed only modest cognitive effects over three years.

N-acetylcysteine is an acetylated form of the amino acid cysteine, used clinically as a mucolytic and as the standard antidote for paracetamol (acetaminophen) overdose. Its principal mechanism in both clinical and longevity contexts is replenishment of intracellular cysteine, the rate-limiting precursor for glutathione biosynthesis, thereby restoring the capacity of the γ-glutamyl-cysteinyl-glycine (GSH) system to buffer reactive oxygen species, support mitochondrial redox balance, and facilitate phase II detoxification. Oral bioavailability is moderate and variable due to first-pass metabolism; liposomal and sustained-release formulations are under study. Beyond antioxidant support, NAC modulates NF-κB-mediated inflammatory signaling and may attenuate cysteine-related DNA methylation shifts. As a standalone agent, it has been evaluated in chronic obstructive pulmonary disease, psychiatric disorders, and metabolic disease with mixed results. In the longevity context it is most relevant as the cysteine-donating half of the GlyNAC combination.

NMN is a nucleotide and NAD+ precursor in the salvage pathway, feeding into a coenzyme central to energy metabolism, sirtuin activity, and DNA repair. Oral NMN is absorbed and raises blood NAD+ in humans, but evidence for clinical longevity benefits remains limited. Trials report modest improvements on specific endpoints such as the 6-minute walk test, muscle insulin sensitivity, or grip strength; large, long-term outcome studies are lacking. NMN's US dietary supplement status was contested from 2022 to 2025, when the FDA reversed its earlier drug-exclusion ruling and confirmed that NMN may lawfully be marketed as a dietary supplement; regulatory status in the EU and other regions varies.

NR is a vitamin B3 form and NAD+ precursor that is metabolized via salvage pathways to increase NAD+, with NMN as a possible intermediate. Human trials reliably show that oral NR raises blood NAD+ and/or related metabolites and is well tolerated. Evidence for downstream clinical benefits, such as improved physical performance, metabolic health, or healthspan, is mixed and largely confined to small, short-duration studies.

Eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) are long-chain polyunsaturated fatty acids found principally in fatty fish and fish oil (with algal supplements as the primary source for vegans). Their principal dietary precursor, alpha-linolenic acid (ALA), is found in flaxseed, chia, and walnuts, but conversion to EPA and DHA in humans is inefficient and highly variable. EPA and DHA are incorporated into cell membranes altering fluidity and lipid-raft composition, and serve as substrates for anti-inflammatory specialized pro-resolving mediators (SPMs) including resolvins and protectins, in contrast to the pro-inflammatory eicosanoids generated from omega-6 arachidonic acid. At pharmacological doses (≥2 g/day EPA+DHA), they reduce serum triglycerides by 20–50%; the REDUCE-IT trial showed that 4 g/day icosapent ethyl (a highly purified EPA ethyl ester) reduced major cardiovascular events in statin-treated hypertriglyceridemic patients, though the mineral oil placebo has been questioned. Observational data consistently associate higher oily-fish intake and blood omega-3 index with lower all-cause and cardiovascular mortality; supplementation trials in generally healthy populations show more modest and inconsistent benefits.

Pterostilbene is a dimethylated stilbene analogue of resveratrol naturally present in blueberries, grapes, and Pterocarpus marsupium heartwood. The two methoxy groups replacing the hydroxyl groups of resveratrol substantially increase lipophilicity and metabolic stability, conferring approximately two- to fourfold higher oral bioavailability and a longer half-life compared with resveratrol. Like resveratrol, it is studied as a putative SIRT1 activator and AMPK modulator, and additionally activates PPARα, relevant to fat oxidation. In rodent models it improves cognitive function, reduces inflammatory and oxidative markers, and extends lifespan in some strains. Human clinical data are limited to small trials examining lipid profiles, blood pressure, and antioxidant markers, with modest and inconsistent effects; a randomized human trial (Riche et al. 2014, NCT01267227) reported LDL elevation at higher pterostilbene doses in the monotherapy arm — a finding notable enough that ChromaDex subsequently ceased new pterostilbene ingredient orders. No robust evidence supports anti-aging benefit in humans, and long-term safety data are sparse.

Quercetin is a flavonoid abundant in onions, apples, capers, and berries with antioxidant and anti-inflammatory activity. It is investigated as a senolytic, though standalone activity is inconsistent in human cell models; the combination with dasatinib (D+Q) is the regimen actually studied in early human senolytic trials. Standalone supplementation has shown small, inconsistent blood pressure effects mainly in hypertensive populations, and bioavailability is low. Human anti-aging evidence is preliminary.

Resveratrol is a stilbene polyphenol found in grape skins, red wine, and Japanese knotweed. It is studied as a putative sirtuin (SIRT1) activator and AMPK modulator, with effects on inflammation and mitochondrial function in preclinical models. Human trials have produced inconsistent results, and oral bioavailability is poor. There is currently no robust evidence that resveratrol supplementation extends human lifespan or healthspan.

Spermidine is a naturally occurring polyamine found in wheat germ, aged cheese, soy, and mushrooms, though content varies widely by source and processing. It induces autophagy, the cellular recycling process implicated in aging, and extends lifespan in yeast, worms, flies, and mice. In humans, dietary intake correlates with lower mortality in observational data; limited preliminary trials have explored possible cognitive signals, but results are not definitive. Causal effects on human longevity are not yet established.

Sulforaphane is an isothiocyanate generated when broccoli, broccoli sprouts, and other cruciferous vegetables are chewed or chopped. It activates the Nrf2 pathway, upregulating antioxidant and phase II detoxification enzymes. Human studies report effects on biomarkers of oxidative stress, inflammation, and cardiometabolic risk, with promising but mixed signals in autism and cancer chemoprevention. Long-term clinical outcomes from sulforaphane supplementation are not yet established.

Taurine is a sulfur-containing non-proteinogenic amino acid synthesized in humans from cysteine via the cysteine sulfinic acid pathway, with dietary intake from animal foods — particularly shellfish, dark poultry meat, and fish — contributing substantially to circulating levels. It is highly concentrated in heart, skeletal muscle, retina, and neurons, where it acts as an osmolyte, modulates intracellular calcium handling, stabilizes mitochondrial membrane potential, and attenuates oxidative and endoplasmic-reticulum stress. A landmark 2023 paper by Singh et al. in Science reported that taurine levels in blood decline markedly with age in mice, monkeys, and humans, and that supplementing physiological amounts of taurine extended median lifespan in both male and female C57BL/6J mice (by approximately 10–12%) and improved several health metrics in middle-aged monkeys; mechanistic studies implicated suppression of cellular senescence, inflammation, DNA damage, and mitochondrial dysfunction. In humans, taurine association with longevity is observational only, and no interventional evidence for lifespan extension exists. A 2025 NIH-led re-analysis (Marcangeli et al., Aging Cell 2025; companion work by Fang et al., Science 2025) found that circulating taurine often increases or remains stable with age in humans, monkeys, and mice, directly challenging the central age-related decline narrative of Singh 2023. Taurine is present in energy drinks and is sold as a supplement; at common doses it appears safe in adults, but long-term high-dose data in humans are limited.