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Abstract PurposeUric acid (UA), the end product of purine metabolism, serves as a potent deoxidant of the brain. UA may therefore be related to psychological activities that are culturally endorsed and normatively promoted, insofar as such activities would require high levels of cortical processing, and thus, gradually expose the brain to a greater oxidation risk. We tested this analysis in Japan, a society that values interdependence of the self with others. MethodsMiddle-aged Japanese adults (N = 243) were tested twice for the serum UA concentration, with five years in-between. Moreover, an assortment of measures assessing culturally sanctioned traits (those related to interdependence) and culturally non-sanctioned traits (those related to independence) were collected. ResultsWe found that the baseline levels of interdependence predicted an increase in the UA in the next five years. In contrast, there was no such effect for independence. Moreover, the effect of interdependence on the UA increase was mediated by cognitive effort in various domains (such as work, finance, and social relations), suggesting that the culturally sanctioned traits increased cognitive effort devoted to mundane everyday activities, which in turn, predicted the UA to increase over time. Notably, baseline UA levels did not affect changes in psychological traits. ConclusionInterpreting these results in light of UA’s role as a potent antioxidant for brain tissues, we propose that higher UA levels may support metabolically demanding actions aligned with culturally sanctioned practices, particularly those associated with interdependence in the Japanese context.