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Overall health: Sleep quality, nutrition, stress levels, and age all affect healing capacity

Published preclinical data in rodents suggests doses equivalent to 200mg+ in humans produce off-target effects on folate metabolism and S-adenosylmethionine (SAMe) pools

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Cartilage faces even greater obstacles given avascular nature (no blood vessels penetrating tissue), low cell density (chondrocytes sparse within extensive extracellular matrix), minimal metabolic activity (slow turnover and repair), and mechanical loading challenges (constant stress impeding healing)