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Lactotripeptides and antihypertensive effects: a critical review

  • Esther Boelsma (a1) and Joris Kloek (a2)
  • DOI:
  • Published online: 05 December 2008

Hypertension or high blood pressure is a significant health problem worldwide. Typically, lifestyle changes, including adopting a healthy diet, are recommended for people with an elevated blood pressure. Lactotripeptides are bioactive milk peptides with potential antihypertensive properties in man. These peptides, as part of a food product or as nutraceutical, may contribute to the prevention and treatment of hypertension. This paper reviews the current evidence of the blood pressure control properties of lactotripeptides in man. Blood pressure-lowering effects of lactotripeptides are typically measured after 4–6 weeks of treatment. However, in some cases, a blood pressure response has been observed after 1–2 weeks. Maximum blood pressure reductions approximate 13 mmHg (systolic blood pressure) and 8 mmHg (diastolic blood pressure) after active treatment compared with placebo, and are likely reached after 8–12 weeks of treatment. Effective dosages of lactotripeptides range from 3·07 to 52·5 mg/d. Evidence indicates that lactotripeptides are only effective at elevated blood pressure; no further lowering of normal blood pressure has been observed. Concomitant intake of antihypertensive medication does not seem to influence the potency of lactotripeptides to lower blood pressure. Similarly, ethnicity has not been found to influence the extent of lactotripeptide-induced blood pressure lowering. Based on the currently available data, lactotripeptides appear to be safe and effective. Thus, they can be part of a healthy diet and lifestyle to prevent or reduce high blood pressure.

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*Corresponding author: Dr E. Boelsma, fax +31 30 694 49 28, email
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1CM Lawes , S Vander Hoorn & A Rodgers (2008) International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet 371, 15131518.

2R Collins , R Peto , S MacMahon , (1990) Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 335, 827838.

3S MacMahon , R Peto , J Cutler , (1990) Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335, 765774.

5Prospective Studies Collaboration (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360, 19031913.

6NR Cook , J Cohen , PR Hebert , (1995) Implications of small reductions in diastolic blood pressure for primary prevention. Arch Intern Med 155, 701709.

8MC Houston (2007) Treatment of hypertension with nutraceuticals, vitamins, antioxidants and minerals. Expert Rev Cardiovasc Ther 5, 681691.

9GN Thomas , BM Cheung , SY Ho , (2007) Overview of dietary influences on atherosclerotic vascular disease: epidemiology and prevention. Cardiovasc Hematol Disord Drug Targets 7, 8797.

10I Rudkowska & PJ Jones (2007) Functional foods for the prevention and treatment of cardiovascular diseases: cholesterol and beyond. Expert Rev Cardiovasc Ther 5, 477490.

11BA Murray & RJ FitzGerald (2007) Angiotensin converting enzyme inhibitory peptides derived from food proteins: biochemistry, bioactivity and production. Curr Pharm Des 13, 773791.

14R Lopez-Fandino , J Otte & J van Camp (2006) Physiological, chemical and technological aspects of milk-protein-derived peptides with antihypertensive and ACE-inhibitory activity. Int Dairy J 16, 12771293.

18J Sano , K Ohki , T Higuchi , (2005) Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension. J Med Food 8, 423430.

25K Aihara , O Kajimoto , H Hirata , (2005) Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension. J Am Coll Nutr 24, 257265.

28CD Brown , M Higgins , KA Donato , (2000) Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res 8, 605619.

30JF Reckelhoff (2001) Gender differences in the regulation of blood pressure. Hypertension 37, 11991208.

31T Jauhiainen , H Vapaatalo , T Poussa , (2005) Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement. Am J Hypertens 18, 16001605.

32World Health Organization, International Society of Hypertension Writing Group (2003) 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 21, 19831992.

34MR Law , NJ Wald , JK Morris , (2003) Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. Br Med J 326, 14271431.

35S Mizushima , K Ohshige , J Watanabe , (2004) Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men. Am J Hypertens 17, 701706.

37PM Kearney , M Whelton , K Reynolds , (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365, 217223.

38J Tuomilehto , J Lindstrom , J Hyyrynen , (2004) Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. J Hum Hypertens 18, 795802.

40PJ Anderson , JA Critchley & B Tomlinson (1996) A comparison of the pharmacokinetics and pharmacodynamics of cilazapril between Chinese and Caucasian healthy, normotensive volunteers. Eur J Clin Pharmacol 50, 5762.

41S Vaidyanathan , J Jermany , C Yeh , (2006) Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects. Br J Clin Pharmacol 62, 690698.

43Y Nakamura , N Yamamoto , K Sakai , (1995) Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J Dairy Sci 78, 777783.

46M Nurminen , M Sipola , H Kaarto , (2000) α-Lactorphin lowers blood pressure via radiotelemetry in normotensive and spontaneously hypertensive rats. Life Sci 66, 15351543.

47W Maes , J Van Camp , V Vermeirssen , (2004) Influence of the lactokinin Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR) on the release of endothelin-1 by endothelial cells. Regul Pept 118, 105109.

48T Hirota , K Ohki , R Kawagishi , (2007) Casein hydrolysate containing the antihypertensive tripeptides Val-Pro-Pro and Ile-Pro-Pro improves vascular endothelial function independent of blood pressure-lowering effects: contribution of the inhibitory action of angiotensin-converting enzyme. Hypertens Res 30, 489496.

51MF Engberink , EG Schouten , FJ Kok , (2008) Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial. Hypertension 51, 399405.

52PS Allender , JA Cutler , D Follmann , (1996) Dietary calcium and blood pressure: a meta-analysis of randomized controlled trials. Ann Intern Med 124, 825831.

53LE Griffith , GH Guyatt , RJ Cook , (1999) The influence of dietary and nondietary calcium supplementation on blood pressure: an updated meta-analysis of randomized controlled trials. Am J Hypertens 12, 8492.

54SH Jee , ER Miller III, E Guallar , (2002) The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens 15, 691696.

55LA van Mierlo , LR Arends , MT Streppel , (2006) Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials. J Hum Hypertens 20, 571580.

56SL Linas (1991) The role of potassium in the pathogenesis and treatment of hypertension. Kidney Int 39, 771786.

58P Elliott , H Kesteloot , LJ Appel , (2008) INTERMAP Cooperative Research Group. Dietary phosphorus and blood pressure: international study of macro- and micro-nutrients and blood pressure. Hypertension 51, 669675.

59GK Grimble (1994) The significance of peptides in clinical nutrition. Annu Rev Nutr 14, 419447.

61BK Bernard , Y Nakamura , I Bando , (2005) Studies of the toxicological potential of tripeptides (l-valyl-l-prolyl-l-proline and l-isoleucyl-l-prolyI-l-proline): II. Introduction. Int J Toxicol 24, Suppl. 4, 511.

62MP Dent , S O'Hagan , WH Braun , (2007) A 90-day subchronic toxicity study and reproductive toxicity studies on ACE-inhibition of lactotripeptide. Food Chem Toxicol 45, 14681477.

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