Kazuhito Ohsawa

Producibility and digestibility of antihypertensive beta-casein tripeptides, Val-Pro-Pro and Ile-Pro-Pro, in the gastrointestinal tract: analyses using an in vitro model of mammalian gastrointestinal digestion.

Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) are antihypertensive tripeptides isolated from milk fermented with Lactobacillus helveticus and inhibit angiotensin-converting enzyme (ACE). We investigated whether these peptides were generated from beta-casein by digestive enzymes and whether they were resistant to enzymatic hydrolysis, using an in vitro model. VPP and IPP were not generated from beta-casein by gastrointestinal enzymes; instead, a number of longer peptides including VPP and IPP sequences were detected. The fermentation step would therefore be necessary to produce these antihypertensive tripeptides. VPP and IPP themselves were hardly digested by digestive enzymes, suggesting that orally administered VPP and IPP remain intact in the intestine, retaining their activity until adsorption. The present study also demonstrated that various functional peptide sequences in beta-casein were resistant to gastrointestinal enzymes. There may be a strong correlation between the resistance of peptides to gastrointestinal digestion and their real physiological effects after oral administration.

Lactobacillus helveticus-fermented milk improves learning and memory in mice

Abstract Objectives To investigate the effects of Calpis sour milk whey, a Lactobacillus helveticus–fermented milk product, on learning and memory. Methods We evaluated improvement in scopolamine-induced memory impairment using the spontaneous alternation behaviour test, a measure of short-term memory. We also evaluated learning and working memory in mice using the novel object recognition test, which does not involve primary reinforcement (food or electric shocks). A total of 195 male ddY mice were used in the spontaneous alternation behaviour test and 60 in the novel object recognition test. Results Forced orally administered Calpis sour milk whey powder (200 and 2000 mg/kg) significantly improved scopolamine-induced cognitive impairments (P < 0.05 and P < 0.01, respectively) and object recognition memory (2000 mg/kg; P < 0.05). Discussion These results suggest that Calpis sour milk whey may be useful for the prevention of neurodegenerative disorders, such as Alzheimers disease, and enhancing learning and memory in healthy human subjects; however, human clinical studies are necessary.

Lactobacillus helveticus-fermented milk containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) improves cognitive function in healthy middle-aged adults: a randomised, double-blind, placebo-controlled trial

Abstract This study aimed to determine the effects of a Lactobacillus helveticus-fermented milk drink containing lactononadecapeptide (NIPPLTQTPVVVPPFLQPE) on the cognitive function of healthy middle-aged adults. A randomised, double-blind controlled study was conducted in healthy participants who were randomly assigned to receive a L. helveticus-fermented milk drink (190u2009g/day) or the equivalent amount of a placebo drink once a day for eight weeks. Cognitive function was evaluated using the Japanese version of the repeatable battery for the assessment of neuropsychological status (RBANS) test. There was a statistically significant improvement in the total score, attention score, and delayed memory score of participants who received the L. helveticus-fermented milk drink. There was also a significant difference in the attention score between the placebo and test groups after eight weeks (pu2009=u2009.028). Therefore, supplementation of healthy middle-aged adults with a L. helveticus-fermented milk drink for eight weeks improved both attention and delayed memory.

Identification of peptides present in sour milk whey that ameliorate scopolamine-induced memory impairment in mice

Abstract Cognitive impairment is treated with cholinesterase inhibitors that slow cognitive decline but cause significant adverse effects. Functional foods that improve memory without such effects would therefore be valuable. We reported that unidentified components of sour milk whey produced by fermentations using Lactobacillus helveticus and Saccharomyces cerevisiae improved memory in a mouse model of scopolamine-induced memory impairment. Here, we show that casein-derived peptides were the most active components of orally administered fractions of this milk product. Of five peptides tested, β-casein (residues 73–91) was the most effective for ameliorating scopolamine-induced cognitive deficits, as indicated by a significantly higher percentage of alternations of mice orally administered 0.05u2009nmol/kg peptide (58.0u2009±u20099.3%) versus vehicle (51.0u2009±u20095.8%). This orally active peptide may improve cognitive function of patients with dementia. Graphical Abstract