Impact of N-PEP-12 Supplementation on Attentional Performance and Mental Wellbeing in Healthy Adults with Subjective Cognitive Complaints: A Randomized, Placebo-Controlled Trial.
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, with a significant group-by-visit interaction (p = 0.003) in a multivariate repeated-measures model.
Key Findings
Results
The multivariate repeated-measures model showed a significant group-by-visit interaction for the three primary attention outcomes analyzed jointly.
Group-by-visit interaction: p = 0.003
Significant effect of visit: p < 0.001
No significant main effect of treatment arm: p = 0.133
This indicates a time-dependent treatment effect rather than an overall group difference
This result was confirmed in a sensitivity analysis population where missing values were imputed under assumptions least favorable to the active arms
Results
At 90 days, both N-PEP-12 dose groups showed greater improvements than placebo in alertness and attention and memory omissions in exploratory endpoint-specific comparisons.
Improvements were observed in alertness, attention omissions, and memory omissions
These comparisons are described as exploratory
The two active doses were 45 mg and 90 mg of N-PEP-12
Assessments were performed at baseline and after 30, 90, and 180 days
Results
Both N-PEP-12 dose groups showed improvements in working memory as measured by WAIS-IV Digit Span Forward and Backward scores at 90 days.
Digit Span Forward and Backward scores improved in both N-PEP-12 groups compared to placebo
These were secondary outcome measures
Results are described as exploratory endpoint-specific comparisons
The WAIS-IV Digit Span was used to assess working memory
Results
Participants initially assigned to placebo who switched to N-PEP-12 90 mg in an uncontrolled extension phase showed comparable improvements to those who had received active treatment throughout.
The extension phase was uncontrolled, with all participants receiving active treatment
Placebo participants switched to N-PEP-12 90 mg during the extension phase
The authors note these observations are exploratory
The total study duration included assessments at baseline, 30, 90, and 180 days
Results
Adverse events were infrequent and similarly distributed across all three treatment groups.
No significant safety signal was identified for either N-PEP-12 dose (45 mg or 90 mg)
The study enrolled 276 participants aged 50–75 years
The trial was prospective, randomized, double-blind, and placebo-controlled
Participants had subjective cognitive complaints but no clinically significant cognitive impairment
Methods
The study population consisted of 276 healthy middle-aged and older adults aged 50–75 years with subjective cognitive complaints and no clinically significant cognitive impairment.
Participants were randomized to placebo, N-PEP-12 45 mg, or N-PEP-12 90 mg
The trial design was prospective, randomized, double-blind, and placebo-controlled
Primary outcomes were Test of Attentional Performance measures
Secondary outcomes included perceived stress, mood, sleep quality, and EQ-5D-5L visual analog scale
Background
Subjective cognitive complaints in middle-aged and older adults may reflect early cognitive changes alongside alterations in stress, mood, sleep, and quality of life.
SCCs are described as common in middle-aged and older adults
N-PEP-12 is characterized as a peptide-based nutritional supplement with potential neuroprotective effects
Evidence of N-PEP-12 benefits in healthy adults with SCCs was described as limited prior to this trial
The study aimed to evaluate effects on attention, cognitive function, and mental wellbeing
What This Means
This research tested whether a peptide-based nutritional supplement called N-PEP-12 could improve attention, memory, and mental wellbeing in 276 healthy adults between the ages of 50 and 75 who reported noticing changes in their own thinking and memory (called subjective cognitive complaints), but who did not have a diagnosed cognitive disorder. Participants were randomly assigned to take either a placebo, a 45 mg dose of N-PEP-12, or a 90 mg dose of N-PEP-12 for up to 180 days, and their cognitive performance was measured at multiple time points using standardized tests.
The study found that the pattern of improvement over time differed between the groups receiving N-PEP-12 and those receiving placebo, with a statistically significant interaction between treatment group and time point. When looking specifically at the 90-day mark, both N-PEP-12 groups showed greater improvements than placebo in measures of alertness, attention accuracy, and working memory (the ability to hold and manipulate information in mind). People who started on placebo and later switched to active treatment during an extension phase of the study also showed similar improvements, though these results are considered exploratory. The supplement was well tolerated, with adverse events being rare and similar across all groups.
This research suggests that N-PEP-12 supplementation may help support attention and working memory in middle-aged and older adults who are noticing age-related changes in their cognition but are otherwise healthy. The authors note that these findings are preliminary and exploratory in several respects, and they call for further investigation. The results provide a basis for larger and longer studies to more definitively evaluate N-PEP-12 as a nutritional approach to supporting cognitive health during normal aging.
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Chira D, Jemna N, Verișezan-Roșu O, Buruiană A, Strilciuc &, Chelaru V, et al.. (2026). Impact of N-PEP-12 Supplementation on Attentional Performance and Mental Wellbeing in Healthy Adults with Subjective Cognitive Complaints: A Randomized, Placebo-Controlled Trial.. Nutrients. https://doi.org/10.3390/nu18162739