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Studies of the Toxicological Potential of Tripeptides (L-Valyl-L-prolyl-L-proline and L-Isoleucyl-L-prolyl-L-proline): II. Introduction
Bruce K. Bernard
SRA International Inc., Washington, DC, USA
Yasunori Nakamura
Product Development Laboratory, Calpis Co., Ltd., Sagamihara, Kanagawa, Japan
Izuki Bando
Quality Assurance Department, Calpis Co., Ltd., Sagamihara, Kanagawa, Japan
John H. Mennear
Campbell University, School of Pharmacy, Buies Creek, North Carolina, USA
Correspondence: Address correspondence to Bruce K. Bernard, PhD, President, SRA International, Inc., 1920 L Street, NW, Suite 420, Washington, DC 20036, USA. E-mail:bernard{at}sra-intl.com
The consumption of fermented milk to maintain good health, including the maintance of normal blood pressure, is an ancient tradition in a number of areas of the world (e.g., East Asia, France). Recent studies have suggested that fermented milk has a normotensive effect in hypertensive rats and humans, but no effect on blood pressure in normotensive rats and humans. Two tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP), have been identified as possessing significant angiotensin-converting enzyme inhibitory activity and are therefore believed to be the source of the normotensive effects. This document, the second of nine chapters, provides information on these two tripeptides, including physical/chemical properties, molecular weights, chemical structures, normal consumption in the diet, manufacturing information, regulatory approval in Japan, and Japanese consumption of food containing enhanced levels of VPP plus IPP. In addition, the results of studies in rats and humans conducted to evaluate the effect of these substances on blood pressure are presented. The research suggests that in adult normotensive volunteers, consumption of up to 7.92 mg of VPP and 4.52 mg IPP daily for 2 weeks causes neither clinical signs nor biologically meaningful effects on systolic or diastolic blood pressure, pulse rate, or clinical pathology (serum chemistry or hematology). However, when a similar study was performed using mildly and moderately hypertensive adults as subjects and they consumed 2.52 mg of VPP and 1.64 mg of IPP per day, a significant drop in systolic blood pressure was detected for a prolonged time interval. This chapter also introduces the issue of safety testing for these substances and describes the information to be found in the subsequent seven chapters.
Key Words: Food Ingredient • Generally Recognized as Safe (GRAS) • IPP • Normotensive Effects • Tripeptides • VPP
International Journal of Toxicology, Vol. 24, No. 4 Suppl,
5-11 (2005)
DOI: 10.1080/10915810500259531
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