title: Ile-Pro-Pro and Val-Pro-Pro tripeptide-containing milk product has acute blood pressure lowering effects in mildly hypertensive subjects.
abstract: Casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) lower blood pressure (BP) in long-term clinical studies. Their acute effects on BP and vascular function, important for daily dosing scheme, were studied in a placebo-controlled double-blind crossover study using a single oral dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro as well as plant sterols. Twenty-five subjects with untreated mild hypertension received in random order 250 g of study product (25 mg peptides and 2 g plant sterols) or placebo. Ambulatory BP was monitored for 8 h post-dose and arterial stiffness measured by pulse wave analysis at 2, 4, and 8 h. Blood and urine samples were analyzed for markers of the renin-angiotensin system (RAS) and endothelial function. Baseline adjusted treatment effect for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial BP was -2.1 mmHg (95% CI: -4.1 to -0.1, p = 0.045), -1.6 mmHg (95% CI: -3.1 to -0.1, p = 0.03), and -1,9 mmHg (95% CI: -3-3 to -0.4, p = 0.0093), respectively, in favor of the active treatment for 8 h post- dose. No significant differences between the treatments were seen in brachial or aortic augmentation index, pulse wave velocity, or markers of RAS. Urinary excretion of cGMP, the second messenger of endothelial nitric oxide, was higher in the active group vs. placebo (p = 0.01). The results indicate that a single dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols acutely lowers brachial SBP and DBP in mildly hypertensive subjects.
authors.affiliation: Valio Ltd., R&D, Helsinki, Finland. anu.turpeinen@valio.fi
authors.forename: Anu M
authors.initials: AM
authors.lastname: Turpeinen
authors.forename: Pauliina I
authors.initials: PI
authors.lastname: Ehlers
authors.forename: Anne S
authors.initials: AS
authors.lastname: Kivimäki
authors.forename: Salme
authors.initials: S
authors.lastname: Järvenpää
authors.forename: Iris
authors.initials: I
authors.lastname: Filler
authors.forename: Erol
authors.initials: E
authors.lastname: Wiegert
authors.forename: Eberhard
authors.initials: E
authors.lastname: Jähnchen
authors.forename: Heikki
authors.initials: H
authors.lastname: Vapaatalo
authors.forename: Riitta
authors.initials: R
authors.lastname: Korpela
authors.forename: Frank
authors.initials: F
authors.lastname: Wagner
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D043302:Cultured Milk Products / Q000737:chemistry; D006152:Cyclic GMP / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D010840:Phytosterols / Q000494:pharmacology / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D009842:Oligopeptides; D010840:Phytosterols; C489032:isoleucyl-prolyl-proline; C489031:valyl-prolyl-proline; D006152:Cyclic GMP