Effects of <i>N</i>-Acetylmannosamine (ManNAc) on Cognitive and Psychological Function in Middle-Aged and Older Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: To delay the onset of dementia with age, it is important for healthy adults to take preventive measures before cognitive decline occurs. Cognitive function decline is often associated with mood disorders such as depression. N-acetylmannosamine (ManNAc) showed activity in a screening assay for components that induced the generation of orexin-producing neurons. Orexins are neuropeptides involved in the regulation of various bodily functions, such as cognitive and psychological function. Therefore, we aimed to examine the effects of ManNAc intake on cognitive and psychological function in middle-aged and older humans. Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the impact of ManNAc on cognitive and psychological functions in middle-aged and older healthy participants. Eighty participants were enrolled and randomly divided into active and placebo groups. The participants consumed either food containing ManNAc 8.8 mg or food without ManNAc for 12 weeks. As the main outcome, cognitive function was assessed before and after ingestion using the Cognitrax test. The secondary outcome, psychological function, was also examined using the POMS2. Results: The active group showed statistical significance in the “Neurocognitive Index”, which is an assessment of overall cognitive function, in addition to the “Psychomotor Speed”, “Reaction Time”, “Cognitive Flexibility”, “Executive Function”, and “Motor Speed” factors in the Cognitrax test compared to the placebo group (P Conclusions: Overall, ManNAc improved cognitive and psychological functions in middle-aged and older adults.