Background: Preventative measures have recently been taken to reduce the incidence of Alzheimer’s disease worldwide. We previously showed that Met-Lys-Pro (MKP), a casein-derived angiotensin-converting enzyme inhibitory peptide with the potential to cross the blood–brain barrier, attenuated cognitive decline in a mouse model of Alzheimer’s disease. However, the effect of MKP on cognitive function improvement in humans remains unknown. This exploratory study sought to investigate whether MKP intake could improve cognitive function in adults without dementia. Methods: A total of 268 community-dwelling adults without dementia participated in this 24-week randomized controlled trial. Participants were randomly allocated to the MKP (n = 134) or placebo (n = 134) group. The MKP group received four tablets daily, each containing 50 μg MKP, while the placebo group received four dextrin tablets containing no detectable MKP for 24 weeks. Scores on the Japanese version of the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) were used as the primary outcome to compare cognitive function between the MKP and placebo groups. The study products were also evaluated for safety. Results: The intention-to-treat analysis showed that there was no significant difference between the groups in terms of the ADAS-cog total score. Orientation, as measured by the respective ADAS-cog subscale, was significantly improved compared to placebo at 24 weeks post-MKP administration (P = 0.022). No serious adverse events due to MKP intake were observed. Conclusion: To the best of our knowledge, this is the first study to report the effects of MKP on human cognition. These preliminary results suggested the safety of daily MKP intake and its potential to improve orientation in adults without dementia. Further clinical studies are needed to confirm the present findings and the benefits of MKP on cognitive function.

Muscle mass loss is induced by aging, several catabolic diseases, and malnutrition. It is well known that ingestion of whey protein and its hydrolysates (WPH) is effective in stimulating muscle protein synthesis. However, these studies focused on the acute up-regulation of muscle protein synthesis, and few studies have investigated the effect of whey protein and WPH on muscle mass during chronic malnutrition. The aim of the present study was to investigate the effect of 7 days supplementation of whey protein and WPH on muscle reduction in Wistar rats fed a protein-free (PF) diet. Wistar rats were fed either a standard diet (containing 20% protein) or a PF diet during the experimental period. Those fed a PF diet received a dietary supplement containing an amino acid mixture, whey protein, or WPH for 7 days. The weight of the extensor digitorum longus decreased in rats fed a PF diet supplemented with the amino acid mixture or the whey protein. However, this decrease was partially but significantly suppressed in the group fed the WPH supplement. Additionally, administration of WPH induced a postprandial increase in plasma essential amino acids, branched-chain amino acids, and leucine concentration compared with animals fed the amino acid mixture or the whey protein. These results suggest that 7 days supplementation of the diet with WPH suppressed muscle weight loss in rats fed a PF diet

Whey proteins are a rich source of bioactive peptides. Whey protein hydrolysate (WPH) can effectively improve metabolic syndrome and reduce the risk of obesity. Bioactive peptides isolated from various food sources exhibit anti‐obesity effects. However, few reports are available on the identification of anti‐obesity peptides from whey protein. In this study, we aimed to identify anti‐obesity peptides from whey protein. Our findings revealed that WPH suppressed the accumulation of lipid droplets in 3T3‐L1 adipocytes. Anti‐obesity peptides in WPH were identified using amino acid sequencing and LC–MS analysis. Then, the inhibitory effects of the synthetic peptides on adipogenesis were assessed through Oil Red O staining. Two peptides were identified as anti‐adipogenic: LDQW and LKPTPEGDLEIL. Subsequently, real‐time PCR analysis found that several adipogenesis‐related genes, such as peroxisome proliferator‐activated receptor γ, were downregulated in the treatment with these peptides. Furthermore, LDQW and LKPTPEGDLEIL decreased the mRNA expression levels of stearoyl‐coenzyme A desaturase 1 and increased carnitine palmitoyl transferase 1α expression in 3T3‐L1 adipocytes. These findings indicate that LDQW and LKPTPEGDLEIL have anti‐obesity properties and may be beneficial for treating metabolic diseases. This study provides a reference basis for developing new techniques to prevent obesity and related diseases.