公益財団法人 腸内細菌学会/腸内細菌学会 Japan Bifidus Foundation(JBF)/Intestinal Microbiology

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Bioscience and Microflora Vol.23, No.4

Review

Studies on Anti-Hypertensive Peptides in Milk Fermented with Lactobacillus helveticus

Yasunori Nakamura*

Product Development Laboratory, Calpis Co., Ltd., 11-10, 5-chome, Fuchinobe, Sagamihara 229-0006, Japan

Received for publication, August 2, 2004

Milk fermented by Lactobacillus helveticus, a lactic acid bacterium with potent proteolytic activity, had an antihypertensive effect in animal model studies. During the culture process, the biogenic peptides valyl-prolyl-proline and isoleucyl-prolyl-proline were derived from milk protein. These two peptides have been shown to have an inhibitory effect on angiotensin-converting enzyme, which converts angiotensin I to angiotensin II, a strong vasoconstrictor. Pre-clinical and in vitro studies suggest that a portion of the orally ingested dose of these peptides can be absorbed in the intact form from the gastrointestinal tract, can inhibit the tissue renin-angiotensin system, and can produce significant reductions in blood pressure. In clinical studies, fermented milk containing biologically active peptides significantly decreased systolic and diastolic blood pressure in hypertensive subjects. In contrast, no significant effect on blood pressure was observed in normotensives. Based on these observations, it is possible that fermented milk containing valyl-prolyl-proline and isoleucyl-prolyl-proline which could provide a non-pharmacological approach to the management of hypertension. This report reviews a series of studies on antihypertensive peptides in milk fermented with Lactobacillus helveticus and also describes the results of clinical trials including the latest information.

Key words: anti-hypertensive effect; Lactobacillus helveticus; fermented milk; peptide; angiotensin-converting enzyme

*Corresponding author. Mailing address: Product Development Laboratory, Calpis Co., Ltd., 11-10, 5-chome, Fuchinobe, Sagamihara 229-0006, Japan.
phone: +81-42-769-7832. Fax: +81-42-769-7830. E-mail: yasunori.nakamura@calpis.co.jp

Bioscience Microflora 23(4): 131-138, 2004

Full Paper

Effect of Fermented Milk Containing Lactobacillus johnsonii La1 (LC1R) on Defecation in Healthy Japanese Adults
-Double Blind Placebo Controlled Study-

Yoichi Fukushima,1* Toshihiko Yamano,1 Ayako Kusano,2 Mamiko Takada,3 Maho Amano3 and Hisakazu Iino3

  1. Nutrition Business Group, Nestle Japan Ltd., NYK Tennoz Building, 2-2-20, Higashi-Shinagawa, Shinagawa-ku, Tokyo 140-0002, Japan
  2. Clinical Research Division, New Drug Development Research Center, Inc., 452-1, Toiso, Eniwa 061-1405, Hokkaido
  3. Life Science for Living System, Graduate School, Showa Women's University, 1-7, Taishidou, Setagaya-ku, Tokyo 154-8533, Japan

Received April 12, 2004; Accepted for publication, July 23, 2004

To elucidate the effect of fermented milk containing Lactobacillus johnsonii La1 (LC1R) on defecation, a double blind placebo controlled study was conducted. Healthy Japanese adults (24-67 years of age, n = 57, male: 31, female: 26) were randomly divided into two groups, and the subjects in the LC1 group (n = 30) consumed LC1 fermented milk containing L. johnsonii La1 at 1 × 109 cfu/90 g (90 g per day) for 21 days and the subjects in the control group (n = 27) consumed placebo fermented milk without the La1 strain in the same manner. In the subjects of the LC1 group with mild constipation (n = 9), less than one defecation per day in the 3 weeks observation period, defecation frequency both in times per week and days per week significantly increased during consumption of LC1 compared to before consumption (p < 0.05), and the frequency recovered to normal status with at least one defecation per day in 4 out of 9 of subjects (44%) after 3 weeks LC1 consumption. Subjects with mild constipation in the control group (n = 7) showed no significant changes in defecation frequency. The frequency in the subjects with normal defecation did not change in either group. L. johnsonii La1 was found in all feces from 10 subjects in the LC1 group participating in fecal collection, suggesting that La1 strain efficiently reached the gastrointestinal tract as a viable form. Excess amount (360 g per day) of LC1 intake for 2 weeks in the other healthy subjects (n = 10) caused an increase in defecation frequency, which was kept at the normal level of less than twice per day. These results suggest that LC1R, a probiotic fermented milk containing L. johnsonii La1, is beneficial for improving mild constipation without any safety concerns.

Key words: probiotics; Lactobacillus; constipation; double blind placebo controlled study

*Corresponding author. Mailing address: Nutrition Business Group, Nestle Japan Ltd., NYK Tennoz Building, 2-2-20, Higashi-Shinagawa, Shinagawa-ku, Tokyo 140-0002, Japan. Phone: +81-3-5769-6211. Fax: +81-3-5769-6290. E-mail: Yoichi.Fukushima@jp.nestle.com

Bioscience Microflora 23(4): 139-147, 2004

Note

Effects of an Exopolysaccharide (Kefiran) from Lactobacillus kefiranofaciens on Blood Glucose in KKAy Mice and Constipation in SD Rats Induced by a Low-Fiber Diet

Hiroaki Maeda,1* Xia Zhu1 and Tomotari Mitsuoka2

  1. Research and Development Division, Daiwa Pharmaceutical Co., Ltd., 1-16-19, Sangenjaya, Setagaya-ku, Tokyo 154-0024, Japan
  2. Professor Emeritus, The University of Tokyo, 2-10-7, Sugano, Ichikawa 272-0824, Japan

Received July 26, 2004; Accepted for publication, September 2, 2004

The physiologic effects of kefiran, a water-soluble exopolysaccharide, were investigated in the animal studies by oral administration of kefiran. The results in this study showed that kefiran had a hypoglycemic effect in KKAy mice and could improve defecation in the levels of fecal moisture and wet weight of feces in constipated SD rats induced by a low-fiber diet.

Key words: exopolysaccharide; kefiran; blood glucose; constipation

*Corresponding author. Mailing address: Research and Development Division, Daiwa Pharmaceutical Co., Ltd., 1-16-19, Sangenjaya, Setagaya-ku, Tokyo 154-0024, Japan. Phone: +81-3-5430-4050. Fax: +81-3-3422-5399. E-mail: maeda@daiwa-pharm.com

Bioscience Microflora 23(4): 149-153, 2004