Exploratory Analysis of Biomarkers Predictive or Reflective of Ninjin'yoeito Efficacy in Patients With Loss of Appetite or Apathy Attributable to Dementia

Aim This study explored biomarkers related to patient characteristics and the efficacy of Ninjin'yoeito (NYT), a traditional Japanese Kampo medicine, by conducting omics (metabolomic and microbiomic) analyses of plasma and stool samples obtained during a randomized controlled trial targeting anorexia and apathy in patients with dementia. Methods Samples were collected from the control and NYT groups at Weeks 0 and 12. Metabolome analysis was performed using mass spectrometry, whereas microbiome analysis was conducted using 16S metagenome sequencing. Additionally, the metabolic activity of NYT ingredients was evaluated in stool samples. Results Plasma amino acid and phospholipid levels were related to the baseline appetite loss score and its improvement upon NYT administration. The levels of several amino acids, especially hydrophobic amino acids such as branched‐chain amino acids, increased with NYT administration. Meanwhile, gut microbiota diversity did not differ between the groups. The metabolic ability in stool samples was higher in the NYT group. Conclusion This study indicated candidate biomarkers that reflect anorexia and the effects of NYT, suggesting that NYT can enhance appetite and increase the levels of essential nutrients such as amino acids in the body. Trial Registration: Ministry of Health, Labour and Welfare (Japan Registry of Clinical Trials): jRCTs031200079