Immunomodulatory Effects of Multivitamin Complexes Containing Agaricus blazei in Patients Undergoing Curative Resection for Non-Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Multicenter Pilot Trial

<b>Background/Objectives</b>: Surgical resection of non-small-cell lung cancer (NSCLC) often results in temporary suppression of natural killer cell activity (NKA), potentially increasing the risk of recurrence. This study aimed to evaluate whether multivitamin and mineral complexes containing <i>Agaricus blazei</i> could support postoperative immune recovery. <b>Methods</b>: In this randomized, double-blind, placebo-controlled multicenter pilot trial, 66 patients with stage I-III NSCLC received either a supplement or a placebo for 28 days post-surgery. NKA was assessed using an interferon-γ release assay preoperatively, on postoperative days (POD) 1-4, and on POD 30. Immune cell subsets, cytokine levels, clinical parameters, and quality of life were evaluated. <b>Results</b>: Both groups showed a postoperative decline in NKA, with recovery observed by POD 30. Although the increase in NKA was not statistically significant, the treatment group showed a greater relative recovery (17.8% vs. 9.9%, <i>p</i> = 0.104). Immune profiling demonstrated significantly better preservation of T cells (<i>p</i> = 0.026) and B cells (<i>p</i> = 0.001) as well as a greater reduction in monocytes (<i>p</i> = 0.031) in the treatment group. No significant differences were observed in cytokine levels, body mass index, Eastern Cooperative Oncology Group Performance Status, or patient-reported outcomes. <b>Conclusions</b>: Supplementation with a multivitamin and mineral complex containing <i>Agaricus blazei</i> may contribute to favorable immune modulation in patients undergoing curative surgery for NSCLC. Larger long-term trials are warranted to confirm these findings and facilitate clinical application.