Effect of Aptamin C on NK Cell Activity and Cytotoxicity: A Randomized Placebo-Controlled Trial and In Vitro Comparison with Vitamin C

Natural killer (NK) cells are crucial components of innate immunity and rapidly eliminate abnormal cells through ligand–receptor signaling without prior sensitization. Vitamin C is known to enhance NK cell function; however, its susceptibility to oxidation may limit its efficacy in NK cell activation. This study evaluated the efficacy of Aptamin C, a stabilized conjugate of vitamin C and an aptamer, in enhancing NK cell activation. In the in vivo randomized placebo-controlled study, 120 participants were randomized to receive either Aptamin C or placebo, and 109 participants were included in the final analysis. Participants received Aptamin C at a dose of 36.057 mg/day or placebo for 4 weeks. The results showed significant increases in NK cell cytotoxicity after 2 and 4 weeks in the Aptamin C group. Additionally, serum levels of cytokines and cytotoxic granules associated with NK cell activity peaked 4 weeks after Aptamin C intake. Subgroup analysis showed that the enhancing effect of Aptamin C on NK cell activity was mainly observed in participants older than 40 years, whereas no significant effects were detected in participants aged <40 years. In the in vitro study, NK-92 cells treated with Aptamin C were compared with NK-92 cells treated with vitamin C. Aptamin C treatment enhanced proliferation, survival, cytotoxicity, and cytotoxic granule production in NK-92 cells compared with vitamin C treatment. These findings indicate that Aptamin C may effectively promote NK cell activation, particularly in middle-aged and older adults, and suggest its potential as an immunomodulatory supplement for supporting NK cell function.