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Interventions and public health nutrition

Effects of long-term intake of lactotripeptides on cardiovascular risk factors in hypertensive subjects

Abstract

Background/objectives:

Lactobacillus helveticus LBK-16H-fermented milk products containing tripeptides isoleucine-proline-proline and valine-proline-proline lower blood pressure in hypertensive subjects using office and home blood pressure registration. The present study was aimed to evaluate the effects of two doses of these lactotripeptides on 24-h ambulatory blood pressure and lipidomics profiles in mildly hypertensive subjects.

Subjects/methods:

In a randomized, double-blind, placebo-controlled parallel group study, 89 mildly hypertensive subjects ingested, after a 1-month run-in period, a fermented milk drink with 5 mg per day of lactotripeptides during 3 months, and a milk drink with 50 mg per day of lactotripeptides for the following 3 months, or a placebo milk drink without lactotripeptides. Ambulatory blood pressure (24 h) was recorded at baseline and at the end of the intervention periods. Lipidomics profiles were characterized before and after the 6-month intervention.

Results:

After the second intervention period (50 mg per day of lactotripeptides), systolic and diastolic 24-h blood pressures decreased significantly in the peptide, but not in the placebo group. However, the treatment effects −2.6 mm Hg (95% confidence interval (CI): −5.7 to 0.4) in systolic and −1.3 mm Hg (95% CI: −3.4 to 0.8) in diastolic blood pressure did not reach statistic significance. Ingestion of 5 mg per day of lactotripeptides for 3 months did not lower blood pressure. The peptide group was dominated by decrease in multiple phospholipids (PL).

Conclusions:

Ingestion of fermented milk with daily dose of 50 mg of lactotripeptides appears to lower elevated blood pressure slightly from the baseline, but not significantly compared with the placebo group and to induce significant decreases in multiple PL.

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References

  1. Mansia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. 2007 ESH-ESC 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). Blood Press 2007; 16: 135–232.

    Article  PubMed  Google Scholar 

  2. Khan NA, Hemmelgarn B, Herman RJ, Bell CM, Mahon JL, Leiter LA et al. The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2—therapy. Can J Cardiol 2009; 25: 287–298.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Jauhiainen T, Korpela R . Milk peptides and blood pressure. J Nutr 2007; 137 (Suppl 2), S825–S829.

    Article  Google Scholar 

  4. Korhonen H, Pihlanto A . Technological options for the production of health-promoting proteins and peptides derived from milk and colostrum. Curr Pharm Des 2007; 13: 829–843.

    Article  CAS  PubMed  Google Scholar 

  5. Foltz M, Meynen EE, Bianco V, van Platerink C, Koning TM, Kloek J . Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation. J Nutr 2007; 137: 953–958.

    Article  CAS  PubMed  Google Scholar 

  6. Jauhiainen T, Wuolle K, Vapaatalo H, Kerojoki O, Nurmela K, Lowrie C et al. Oral absorption, tissue distribution and excretion of a radiolabelled analog of a milk derived antihypertensive peptide Ile-Pro-Pro in the rat. Int Dairy J 2007; 17: 1209–1211.

    Article  CAS  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    CAS  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Tuomilehto J, Lindström J, Hyyrynen J, Korpela R, Karhunen ML, Mikkola L et al. Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. J Hum Hypertens 2004; 18: 795–802.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. Jauhiainen T, Vapaatalo H, Poussa T, Kyrönpalo 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.

    Article  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Turpeinen A, Kumpu M, Rönnback M, Seppo L, Kautiainen H et al. Antihypertensive and cholesterol-lowering effects of a spread containing bioactive peptides IPP and VPP and plant sterols. J Funct Foods 2009; 1: 260–265.

    Article  CAS  Google Scholar 

  17. 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: H1899–H1903.

    Article  CAS  PubMed  Google Scholar 

  18. Germino FW, Neutel J, Nonaka M, Hendler SS . The impact of lactotripeptides on blood pressure response in stage 1 and stage 2 hypertensives. J Clin Hypertens (Greenwich) 2010; 12: 153–159.

    Article  Google Scholar 

  19. Engberink MF, Schouten EG, Kok FJ, van Mierlo LA, Brouwer IA, Geleijnse JM . Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial. Hypertension 2008; 51: 399–405.

    Article  CAS  PubMed  Google Scholar 

  20. van der Zander K, Bots ML, Bak AA, Koning MM, de Leeuw PW . Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects. Am J Clin Nutr 2008; 88: 1697–1702.

    Article  CAS  PubMed  Google Scholar 

  21. van Mierlo LA, Koning MM, 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.

    Article  CAS  PubMed  Google Scholar 

  22. Pripp AH . Effect of peptides derived from food proteins on blood pressure: a meta-analysis of randomized controlled trials. Food Nutr Res 2008; 52, e-pub ahead of print 18 January 2008 doi:10.3402/fnr.v52i0.1641.

  23. 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: 933–940.

    Article  CAS  PubMed  Google Scholar 

  24. Cicero AFG, Gerocarni G, Laghi L, Borghi C . Blood pressure lowering effects of lactotripetptides assumed as fuctional foods: a meta-analysis of current available clinical trials. J Hum Hypertens 2011; 25: 425–436.

    Article  CAS  PubMed  Google Scholar 

  25. Watson AD . Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res 2006; 47: 2101–2111.

    Article  CAS  PubMed  Google Scholar 

  26. Jänis MT, Laaksonen R, Oresic M . Metabolomic strategies to identify tissue specific effects of cardiovascular drugs. Exp Opin Drug Metab Toxicol 2008; 4: 665–680.

    Article  Google Scholar 

  27. O’Brien E, Asmar R, Beilin L, Imai Y, Mancia G, Mengden T et al. On behalf of the European Society of Hypertension Working Group on Blood Pressure Monitoring. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens 2005; 23: 697–701.

    Article  PubMed  Google Scholar 

  28. Jauhiainen T, Rönnback M, Vapaatalo H, Wuolle K, Kautiainen H, Groop PH et al. Long-term intervention with Lactobacillus helveticus fermented milk reduces augmentation index in hypertensive subjects. Eur J Clin Nutr 2010; 64: 424–431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Masuda O, Nakamura Y, Takano T . Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats. J Nutr 1996; 126: 3063–3068.

    Article  CAS  PubMed  Google Scholar 

  30. Hiltunen TP, Suonsyrjä T, Hannila-Handelberg T, Paavonen KJ, Miettinen HE, Strandberg T et al. Predictors of antihypertensive drug responses: initial data from a placebo-controlled, randomized, cross-over study with four antihypertensive drugs (The GENRES Study). Am J Hypertens 2007; 20: 311–318.

    Article  CAS  PubMed  Google Scholar 

  31. Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  PubMed  Google Scholar 

  32. Katajamaa M, Miettinen J, Oresic M . MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data. Bioinformatics 2006; 22: 634–636.

    Article  CAS  PubMed  Google Scholar 

  33. Barker M, Rayens W . Partial least squares for discrimination. J Chemometrics 2003; 17: 166–173.

    Article  CAS  Google Scholar 

  34. Selmer RM, Kristiansen IS, Haglerod A, Graff-Iversen S, Larsen HK, Meyer HE et al. Cost and health consequences of reducing the population intake of salt. J Epidemiol Commun Health 2000; 54: 697–702.

    Article  CAS  Google Scholar 

  35. Head GA, Mihailidou AS, Duggan KA, Beilin LJ, Berry N, Brown MA et al. Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study. BMJ 2010; 340: c1104.

    Article  PubMed  PubMed Central  Google Scholar 

  36. 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; 26: 1–7.

    Google Scholar 

  37. Schwab U, Seppänen-Laakso T, Yetukuri L, Agren J, Kolehmainen M, Laaksonen DE et alGENOBIN Study Group Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism—the GENOBIN study. PLoS One 2008; 3: e2630.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sweeney G, Nazir D, Clarke C, Goettsche G . Ethanolamine and choline phospholipids in nascent very-low-density lipoprotein particles. Clin Invest Med 1996; 19: 243–250.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Tuulikki Seppänen-Laakso for skillful assistance with the lipidomic analysis, Anu Turpeinen, PhD, for her skilled help with the manuscript, Kimmo Kontula, MD, Professor, for valuable discussions on blood pressure evaluations, and Aino Siltari for her technical assistance in typing the manuscript. The test products were provided by Valio Ltd, Finland. All authors approved the final version of the manuscript.

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Correspondence to R Korpela.

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Competing interests

TJ is and RK was an employee of Valio Ltd. HV was consulting for Valio Ltd, and at present Santen Ltd and MSD Finland Ltd, Finland. Valio Ltd compensed LN and SJ for their working time.

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Jauhiainen, T., Niittynen, L., Orešič, M. et al. Effects of long-term intake of lactotripeptides on cardiovascular risk factors in hypertensive subjects. Eur J Clin Nutr 66, 843–849 (2012). https://doi.org/10.1038/ejcn.2012.44

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