Impact of N-PEP-12 Supplementation on Attentional Performance and Mental Wellbeing in Healthy Adults with Subjective Cognitive Complaints: A Randomized, Placebo-Controlled Trial.

Background: Subjective cognitive complaints (SCCs) are common in middle-aged and older adults and may reflect early cognitive changes, alongside alterations in stress, mood, sleep, and quality of life. N-PEP-12 is a peptide-based nutritional supplement with potential neuroprotective effects, but evidence of its benefits in healthy adults with SCCs remains limited. Objective: To evaluate the effects of N-PEP-12 supplementation on attention, cognitive function, and mental wellbeing in healthy middle-aged and older adults with SCCs. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 276 participants aged 50-75 years with SCCs and no clinically significant cognitive impairment were randomized to placebo, N-PEP-12 45 mg, or N-PEP-12 90 mg. Assessments were performed at baseline and after 30, 90, and 180 days. Primary outcomes included Test of Attentional Performance measures. Secondary outcomes included WAIS-IV Digit Span Forward and Backward, perceived stress, mood, sleep quality, and EQ-5D-5L visual analog scale. Results: Across the three primary attention outcomes analyzed jointly in a multivariate repeated-measures model, there was a significant group-by-visit interaction (p = 0.003) and a significant effect of visit (p < 0.001), without a significant main effect of treatment arm (p = 0.133), indicating a time-dependent treatment effect. This result was obtained in a sensitivity analysis population in which missing values were imputed under assumptions least favorable to the active arms. In exploratory endpoint-specific comparisons at 90 days, both N-PEP-12 groups showed greater improvements than placebo in alertness, attention omissions and memory omissions, and Digit Span Forward and Backward scores also improved. In a subsequent uncontrolled extension phase, in which all participants received active treatment, participants initially assigned to placebo showed comparable improvements after switching to N-PEP-12 90 mg. These observations are exploratory. Adverse events were infrequent and similarly distributed across groups. Conclusions: N-PEP-12 supplementation was associated with improvements in attention, working memory, and mental wellbeing in healthy middle-aged and older adults with subjective cognitive complaints. These findings support further investigation of N-PEP-12 as a nutritional intervention for early subjective cognitive changes associated with aging.