Lentinus edodes (=Lentinula edodes) is a culinary-medicinal mushroom with a long tradition of use in Asia. The major active substance in L. edodes is a beta-(1-3,1-6)-glucan (lentinan). GlycaNova produces Lentinex®, which contains this beta-glucan from L. edodes mycelia, in a proprietary process that maintains the triple helix molecular structure and high molecular weights. This study was carried out to investigate the effect of Lentinex supplementation on the well-being of adults. We evaluated the effect of Lentinex in healthy adult subjects in a randomized, placebo-controlled, double-blind trial. Sixty-three subjects, randomly allocated to two groups, took orally either 1-2 mL/day Lentinex (1-2 mg beta-glucan) or placebo for four weeks. The participants completed a well-being questionnaire prior to commencing supplementation and again at the end of the in-home study. The results showed an important and statistically significant improvement in well-being over the period in the treated group compared with the placebo group. The degree of improvement in the treated group, including relative to placebo, was higher for subjects who had lower initial well-being than for subjects with higher initial well-being. In conclusion, the lower an individual's initial well-being, the more Lentinex helped.