Abstract
The oral assumption of lactotripeptides Valine–Proline–Proline (VPP) and Isoleucine–Proline–Proline (IPP) as nutraceuticals or functional foods is supposed to improve blood pressure (BP) control by angiotensin-converting enzyme-inhibition. However, data derived from clinical trials have reached conflicting conclusions. To perform a meta-analysis of placebo-controlled clinical trials evaluating the anti-hypertensive effect of lactotripeptides assumed as nutraceuticals or functional foods. Trials identified using a defined search strategy in PubMed were included in the meta-analysis, and their pooled effect was estimated with a random effects model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed. A total of 18 trials have been identified, the clinical data of which have been clearly reported. Pooled effect of peptides was a reduction of −3.73 mm Hg (95% CI: −6.70, −1.76) for systolic blood pressure (SBP) and 1.97 mm Hg (95% CI: −3.85, −0.64) for diastolic blood pressure (DBP). The effect was more evident in Asian patients (SBP=−6.93 mm Hg (95% CI: −10.95, −2.94); DBP=−3.98 mm Hg(95% CI: −5.38, −2.44)) than in Caucasian ones (SBP=−1.17 mm Hg (95% CI: −2.82, 0.72); DBP=−0.52 mm Hg (95% CI: −1.39, 0.13)), and apparently not related to age, baseline BP values, dose of lactotripeptides assumed or length of the treatment. VPP and IPP lactotripeptides assumed as functional foods may significantly reduce SBP particularly in Asian subjects. The relevance of this findings in other ethnicities or associated with different dietary pattern should to be further investigated.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gaziano TA . Cardiovascular disease in the developing world and its cost-effective management. Circulation 2005; 112: 3547–3553.
Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J . Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217–223.
Lawes CM, Vanders HS, Rodgers A . Global burden of blood-pressure related disease, 2001. Lancet 2008; 371: 1513–1518.
McInnes GT . Lowering blood pressure for cardiovascular risk reduction. J Hypertens Suppl 2005; 23: S3–S8.
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007; 25 (6): 1105–1187.
Appel LJ, Giles TD, Black HR, Izzo Jr JL, Materson BJ, Oparil S, et al., American Society of Hypertension Writing Group. ASH position paper: dietary approaches to lower blood pressure. J Clin Hypertens 2009; 11 (7): 358–368.
Miller III ER, Erlinger TP, Appel LJ . The effects of macronutrients on blood pressure and lipids: an overview of the DASH and OmniHeart trials. Curr Atheroscler Rep 2006; 8 (6): 460–465.
Pérez-López FR, Chedraui P, Haya J, Cuadros JL . Effects of the Mediterranean diet on longevity and age-related morbid conditions. Maturitas 2009; 64 (2): 67–79.
Pripp AH . Effect of peptides derived from food proteins on blood pressure: a meta-analysis of randomized controlled trials. Food Nutr Res 2008; 52: 1–9.
Murray BA, FitzGerald RJ . Angiotensin converting enzyme inhibitory peptides derived from food proteins: biochemistry, bioactivity and production. Curr Pharm Des 2007; 13: 773–791.
FitzGerald RJ, Meisel H . Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme. Br J Nutr 2000; 84 (Suppl. 1): S33–S37.
Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T . A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr 1996; 64: 767–771.
Kajimoto O, Nakamura Y, Yada H, Moriguchi S, Hirata H, Takahashi T . Hypotensive effect of sour milk in subjects with mold or moderate hypertension. J Jpn Soc Nutr Food Sci 2001; 54: 347–354.
Kajimoto O, Aihara K, Hirata H, Takahashi R, Nakamura Y . Hypotensive effects of the tablets containing ‘Lactotripeptides (VPP, IPP)’. J Nutr Food 2001; 4 (3): 51–61.
Hirata H, Nakamura Y, Yada H, Moriguchi S, Kajimoto O, Takahashi T . Clinical effect of new sour milk drink on mild or moderate hypertensive subjects. J New Rem Clin 2002; 51 (1): 61–69.
Seppo L, Kerojoki O, Suomalainen T, Korpela R . The effect of a Lactobacillus helveticus LBK-16 H fermented milk on hypertension: a pilot study on humans. Milchwissenschaft 2002; 57: 124–127.
Seppo L, Jauhiainen T, Poussa T, Korpela R . A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am J Clin Nutr 2003; 77: 326–330.
Mizushima S, Ohshige K, Watanabe J, Kimura M, Kadowaki T, Nakamura Y et al. Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men. Am J Hypertens 2004; 17: 701–706.
Tuomilehto J, Lindstrom J, Hyyrynen J, Korpela R, Karhunen M-L, Mikkola L et al. Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with milk hypertension. J Hum Hypertens 2004; 18: 795–802.
Aihara K, Kajimoto O, Hirata H, Takahashi R, Nakamura Y . Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension. J Am Coll Nutr 2005; 24: 257–265.
Jauhiainen T, Vapaatalo H, Poussa T, Kyronpalo S, Rasmussen M, Korpela R . Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement. Am J Hypertens 2005; 18: 1600–1605.
Mizuno S, Matsuura K, Gotou T, Nishimura S, Kajimoto O, Yabune M et al. Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension. Br J Nutr 2005; 94: 84–91.
Sano J, Ohki K, Higuchi T, Aihara K, Mizuno S, Kajimoto O et al. Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension. J Med Food 2005; 8: 423–430.
Engberink MF, Schouten EG, Kok FJ, van Mierlo LAJ, Brouwer IA, Geleijnse JM . Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial. Hypertension 2008; 51 (2): 399–405.
van der Zander K, Bots ML, Bak AAA, Koning MMG, de Leeuw PW . Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects. Am J Clin Nutr 2008; 88: 1697–1702.
van Mierlo LAJ, Koning MMG, van der Zander K, Draijer R . Lactotripeptides do not lower ambulatory blood pressure in untreated whites: results from 2 controlled multicenter crossover studies. Am J Clin Nutr 2009; 89: 617–623.
de Leeuw PW, van der Zander K, Kroon AA, Rennenberg RM, Koning MM . Dose-dependent lowering of blood pressure by dairy peptides in mildly hypertensive subjects. Blood Press 2009; 18 (1–2): 44–50.
Yoshizawa M, Maeda S, Miyaki A, Misono M, Choi Y, Shimojo N et al. Additive beneficial effects of lactotripeptides and aerobic exercise on arterial compliance in postmenopausal women. Am J Physiol Heart Circ Physiol 2009; 297 (5): H1899–H1903.
Cicero AFG, Rosticci M, Veronesi M, Bacchelli S, Strocchi E, Melegari C et al. Haemodynamic effects of lactotripeptides from fermentation by lactobacillus helveticus in normotensive subjects and patients with high-normal blood pressure: a randomized, double-blind, cross-over clinical trial. J Med Food 2010 (in press).
DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.
Higgins JP, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.
Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.
Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F . Methods for Meta-Analysis in Medical Research. John Wiley & Sons: Chichester, UK, 2000.
Bax L, Yu LM, Ikeda N, Tsuruta N, Moons KGM . MIX: comprehensive free software for meta-analysis of causal research data. Version 1.54; 2006 (www.mix-for-meta-analysis.info).
Xu JY, Qin LQ, Wang PY, Li W, Chang C . Effect of milk tripeptides on blood pressure: a meta-analysis of randomized controlled trials. Nutrition 2008; 24 (10): 933–940.
Verdecchia P, Angeli F, Mazzotta G, Ambrosio G, Reboldi G . Angiotensin receptor blockers in hypertension. New insights from Japan. Hypertens Res 2010; 33 (5): 394–397.
Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al., Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007; 369 (9567): 1090–1098.
Law MR, Morris JK, Wald NJ . Use of Blood Pressure Lowering Drugs in the Prevention of Cardiovascular Disease: Meta-analysis of 147 Randomised Trials in the Context of Expectations from Prospective Epidemiological Studies. BMJ 2009; 338: b1665.
Nakamura T, Mizutani J, Sasaki K, Yamamoto N, Takazawa K . Beneficial potential of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro on central blood pressure and hemodynamic index: a preliminary study. J Med Food 2009; 12 (6): 1–6.
Geleijnse JM, Engberink MF . Lactopeptides and human blood pressure. Curr Opin Lipidol 2010; 21 (1): 58–63.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Cicero, A., Gerocarni, B., Laghi, L. et al. Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials. J Hum Hypertens 25, 425–436 (2011). https://doi.org/10.1038/jhh.2010.85
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/jhh.2010.85
Keywords
This article is cited by
-
Longer-term effects of the egg-protein hydrolysate NWT-03 on arterial stiffness and cardiometabolic risk markers in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled, crossover trial
European Journal of Clinical Nutrition (2023)
-
Dietary Intervention to Improve Blood Pressure Control: Beyond Salt Restriction
High Blood Pressure & Cardiovascular Prevention (2021)
-
A double-blind, randomized, crossover trial protocol of whole hemp seed protein and hemp seed protein hydrolysate consumption for hypertension
Trials (2020)
-
Peptidomic and glycomic profiling of commercial dairy products: identification, quantification and potential bioactivities
npj Science of Food (2019)
-
Effect of an egg ovalbumin-derived protein hydrolysate on blood pressure and cardiovascular risk in adults with a mildly elevated blood pressure: a randomized placebo-controlled crossover trial
European Journal of Nutrition (2019)