Curcumin

Curcumin is a polyphenolic compound derived from the dietary spice turmeric, the rhizome of Curcuma longa. ^{[1] [2]} It is the most important active component in turmeric extracts and possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, and antiproliferative activities. ^{[3] [1]} Curcumin is a lipophilic polyphenol that may act as an anticancer, antibiotic, anti-inflammatory, and anti-aging agent. ^[4]

Curcumin's anti-inflammatory properties are related to inhibition of the NF-kB pathway, and it modulates oxidative stress by activating the NRF2 pathway to enhance cellular antioxidant defenses. ^[2] Curcumin may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and by inhibiting pro-aging proteins such as NF-kB and mTOR. ^[5] In model organisms curcumin's lifespan-extension effects have been connected with enhanced superoxide dismutase activity and declined malondialdehyde and lipofuscin levels, and with modulation of longevity-related signaling pathways such as IIS, mTOR, PKA, and FOXO. ^[6]

Active research has demonstrated that curcumin and its metabolite tetrahydrocurcumin increase mean lifespan of at least three model organisms: the nematode roundworm, the fruit fly Drosophila, and the mouse. ^[7] A systematic review of curcumin for healthy aging screened 2256 documents and selected 15 clinical trials, emphasizing effects on cognitive function, neurodegeneration, and muscle health in older adults while concluding that further well-designed clinical trials are essential. ^[8] A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials found that turmeric/curcumin supplementation significantly reduced inflammatory markers including C-reactive protein, TNF-alpha, and IL-6 and improved antioxidant status in adults. ^[9] A comprehensive systematic review and meta-analysis of 103 randomized controlled trials incorporating 7216 participants found high-certainty evidence that curcumin supplementation modifies fasting

A major limitation is that curcumin exhibits poor bioavailability, with low plasma and tissue levels attributed to poor absorption, rapid metabolism, and rapid systemic elimination. ^[1] Phase I clinical trials have shown that curcumin is safe even at high doses in humans, and numerous formulation approaches such as piperine adjuvants, liposomes, nanoparticles, and phospholipid complexes have been developed to improve its bioavailability. ^[1] Excessive intake of curcumin may have adverse effects on the kidneys, heart, liver, blood, and immune system, and its clinical transformation from basic research to application has not been successful. ^[3]