Hostname: page-component-6bf8c574d5-xtvcr Total loading time: 0 Render date: 2025-02-17T02:19:29.488Z Has data issue: false hasContentIssue false
  • English
  • Français

Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension

Published online by Cambridge University Press:  08 March 2007

Seiichi Mizuno ,
Keiichi Matsuura ,
Takanobu Gotou ,
Shingo Nishimura ,
Osami Kajimoto ,
Mitsuharu Yabune ,
Yoshitaka Kajimoto  and
Naoyuki Yamamoto
Seiichi Mizuno
Affiliation:
Food Research Laboratory, Calpis Co. Ltd. Sagamihara, Kanagawa, Japan
Keiichi Matsuura
Affiliation:
Food Research Laboratory, Calpis Co. Ltd. Sagamihara, Kanagawa, Japan
Takanobu Gotou
Affiliation:
Food Research Laboratory, Calpis Co. Ltd. Sagamihara, Kanagawa, Japan
Shingo Nishimura
Affiliation:
Food Research Laboratory, Calpis Co. Ltd. Sagamihara, Kanagawa, Japan
Osami Kajimoto
Affiliation:
Soiken Inc., Toyonaka, Osaka, Japan
Mitsuharu Yabune
Affiliation:
Soiken Inc., Toyonaka, Osaka, Japan
Yoshitaka Kajimoto
Affiliation:
Soiken Inc., Toyonaka, Osaka, Japan
Naoyuki Yamamoto*
Affiliation:
Food Research Laboratory, Calpis Co. Ltd. Sagamihara, Kanagawa, Japan
*
*Corresponding author: Dr Naoyuki Yamamoto, fax +81 042 769 7810, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

We describe a clinical trial to study the efficacy of a casein hydrolysate, prepared using an Aspergillus oryzae protease, containing the major angiotensin-I-converting enzyme inhibitory peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) in a single-blind, placebo-controlled study. A total of 131 volunteers with high-normal blood pressure and mild hypertension were randomly divided into four groups (n 32 or 33 in each group). Each volunteer was given two tablets containing four different dosages of VPP and IPP (VPP+IPP: 0, 1·8, 2·5 and 3·6 mg), daily for 6 weeks. A significant decrease in systolic blood pressure was observed at 6 weeks in the active group receiving 1·8 mg (P<0·01) VPP and IPP; in the active groups receiving either 2·5 mg or 3·6 mg, systolic blood pressure was decreased at both 3 weeks (P<0·05 and P<0·05) and 6 weeks (P<0·001 and P<0·0001) compared with systolic blood pressure measured before treatment. Changes in the systolic blood pressure after 6 weeks of treatment in the four groups were −1·7, −6·3, −6·7 and −10·1 mmHg, and these effects were dose dependent. In addition, a significant difference in systolic blood pressure between the placebo group and the VPP and IPP group receiving 3·6 mg was observed (P<0·001) by two-way ANOVA. The antihypertensive effect was greater in mildly hypertensive subjects (n 20 or 21 in each group) than in any of the other subjects. No significant change of diastolic blood pressure was observed for all the test groups, and no differences in diastolic blood pressure in the test sample groups compared with the placebo group were observed during the test period.

Keywords

Antihypertensive effectClinical studyCasein hydrolysateVPP and IPP
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 1 , July 2005 , pp. 84 - 91
Copyright
Copyright © The Nutrition Society 2005

References

Atkinson, AB, Brown, JI, Lever, AF & Robertson, JI (1980) Combined treatment of severe intractable hypertension with captopril and diuretic. Lancet 2, 105–107.CrossRefGoogle ScholarPubMed
Chalmers, J, Macmahon, S, Mancia, G, Whitworth, J, Beilin, L, Hansson, L, Neal, B, Rodgers, ANi Mhurchu, C & Clark, T (1999) World Health Organisation–International Society of Hypertension guidelines for the management of hypertension. Clinical and Experimental Hypertension 21, 1009–1060.Google Scholar
Conlin, PR, Chow, D, Miller, ER 3rdSvetkey, LP, Lin, PH, Harsha, DW, Moore, TJ, Sacks, FM & Appel, LJ (2000) The effect of dietary patterns on blood pressure control in hypertensive patients: results from the Dietary Approaches to Stop Hypertension (DASH) trial. Am J Hypertension 13, 949–955.CrossRefGoogle ScholarPubMed
Ferguson, RK, Vlasses, PH, Koplin, JR, Shirinian, A, Burke, JF Jr & Alexande, JC (1980) Captopril in severe treatment-resistant hypertension. Am Heart J 99, 579–585.CrossRefGoogle ScholarPubMed
Hata, Y, Yamamoto, M, Ohni, M, Nakajima, K, Nakamura, Y & Takano, T (1996) A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr 64, 767–771.CrossRefGoogle ScholarPubMed
Kajimoto, O, Aihara, K, Hirata, H, Takahashi, R & Nakamura, Y (2001) Hypertensive effects of the tablets containing ‘Lactotripeptides (VPP, IPP)'. J Nutr Food (Japan) 4, 51–61.Google Scholar
Kawasaki, T, Seki, E, Osajima, K, Yoshida, M, Asada, K, Matsui, T & Osajima, Y (2000) Antihypertensive effect of valyl-tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects. J Hum Hypertens 14, 519–523.CrossRefGoogle Scholar
Maeno, M, Yamamoto, N & Takano, T (1996) Identification of an antihypertensive peptide from casein hydrolyzate by a proteinase from Lactobacillus helveticus CP790. J Dairy Sci 79, 1316–1321.CrossRefGoogle Scholar
Maruyama, S, Nakagomi, K, Tomizuka, N & Suzuki, H (1985) Angiotensin I-converting enzyme inhibitor derived from an enzymatic hydrolysate of casein. II. Isolation and bradykinin-potentiating activity on the uterus and the ileum of rats. Agric Biol Chem 49, 1405–1409.Google Scholar
Masuda, O, Nakamura, Y & Takano, T (1996) Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats. J Nutr 126, 3063–3068.CrossRefGoogle ScholarPubMed
Matsumura, N, Fujii, M, Takeda, Y, Sugita, K & Shimizu, T (1993) Angiotensin I-converting enzyme inhibitory peptides derived from bonito bowels autolysate. Biosci Biotech Biochem 57, 695–697.CrossRefGoogle ScholarPubMed
Matsuura, K, Gotou, T, Mizuno, S, Nishimura, S & Yamamoto, N (2005) Quantitative analysis of antihypertensive peptides, Val-Pro-Pro and Ile-Pro-Pro, in casein hydrolyzate using an Aspergillus oryzae protease: an LC-MS method. Milchwissenschaft 60, 24–27.Google Scholar
Meisel, H & Bockelmann, W (1999) Bioactive peptides encrypted in milk proteins: proteolytic activation and thropho-functional properties. Antonie van Leewenhoek 76, 207–215.CrossRefGoogle ScholarPubMed
Miyoshi, S, Ishikawa, H, Kaneko, T, Fukui, F, Tanaka, H & Maruyama, S (1991) Structures and activity of angiotensin-converting enzyme inhibitors in an alpha-zein hydrolysate. Agric Biol Chem 55, 1313–1318.Google Scholar
Mizuno, S, Nishimura, S, Matsuura, K, Gotou, T & Yamamoto, N (2004) Release of short and proline rich antihypertensive peptides from casein hydrolyzate with an Aspergillus oryzae protease. J Dairy Sci 87, 3183–3188.CrossRefGoogle Scholar
Moore, TJ, Vollmer, WM, Appel, LJ, et al. (1999) Effect of dietary patters on ambulatory blood pressure: results from the Dietary Approaches to Stop Hypertension (DASH) trial: DASH collaborative research group. Hypertension 34, 472–477.CrossRefGoogle Scholar
Nakamura, Y, Kajimoto, O, Kaneko, K, Aihara, K, Mizutani, J, Ikeda, N & Kajimoto, Y (2002) Effect of the liquid yogurts containing ‘lactotripeptide (VPP and IPP)’ on high-normal blood pressure. J Nutr Food (Japan) 5, 55–66.Google Scholar
Nakamura, Y, Masuda, O & Takano, T (1996) Decrease of tissue angiotensinI-converting enzyme activity upon feeding sour milk in spontaneously hypertensive rats. Biosci Biotech Biochem 60, 488–489.CrossRefGoogle Scholar
Nakamura, Y, Yamamoto, N, Sakai, K, Okubo, A, Yamazaki, S & Takano, T (1995a) Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J Dairy Sci 78, 777–783.CrossRefGoogle ScholarPubMed
Nakamura, Y, Yamamoto, N, Sakai, K & Takano, T (1995b) Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J Dairy Sci 78, 1253–1257.CrossRefGoogle ScholarPubMed
Seppo, L, Jauhiainen, T, Poussa, T & Korpela, R (2003) A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am J Clin Nutr 77, 326–330.CrossRefGoogle Scholar
Seppo, L, Kerojoki, O, Suomalainen, T & Korpela, R (2002) The effect of a Lactobacillus helveticus LBK-16 H fermented milk on hypertension – a pilot study on humans. Milchwissenschaft 57, 124–127.Google Scholar
Staessen, J (1981) The hypotensive effect of propranolol in captopril-treated patients does not involve the plasma renin-angiotensin-aldosterone system. Clin Sci 61, 441–444.CrossRefGoogle Scholar
Stornello, M, Di Rao, G, Iachello, M, et al. (1983) Hemodynamic and humoral interactions between captopril and nifedipine. Hypertension 5, 154–156.CrossRefGoogle ScholarPubMed
Svetkey, LP, Moore, TJ, Simons-Morton, DG, et al. (2001) DASH collaborative research group Angiotensinogen genotype and blood pressure response in the dietary approaches to top hypertension (DASH) study. J Hypertens 19, 1949–1956.CrossRefGoogle Scholar
Takano, T (1998) Milk derived peptides and hypertension reduction. Int Dairy J 8, 375–381.CrossRefGoogle Scholar
Yamamoto, N, Akino, A & Takano, T (1994) Antihypertensive effects of different kinds of fermented milk in spontaneously hypertensive rats. Biosci Biotech Biochem 58, 776–778.CrossRefGoogle Scholar
Yamamoto, N, Ejiri, M & Mizuno, S (2003) Biogenic peptides and their potential use. Curr Pharmaceut Design 9, 1345–1355.CrossRefGoogle ScholarPubMed
Yamamoto, N & Takano, T (1999) Antihypertensive peptides derived from milk proteins. Nahrung 43, 159–164.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Yamamoto, N, Maeno, M & Takano, T (1999) Purification of the antihypertensive peptide from yogurt-like product. J Dairy Sci 82, 1388–1393.CrossRefGoogle ScholarPubMed
Yokoyama, K, Chiba, H & Yoshikawa, M (1992) Peptide inhibitors for angiotensin I-converting enzyme from thermolysin digest of dried bonito. Biosci Biotechnol Biochem 56, 1541–1545.CrossRefGoogle ScholarPubMed