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.

Casein-Derived Lactotripeptides Reduce Systolic and Diastolic Blood Pressure in a Meta-Analysis of Randomised Clinical Trials

“…A total of 30 studies met the selection criteria. The reason for study exclusion included studies which were not randomised ( n = 3) [ 27 , 28 , 29 ], trials investigating postprandial responses ( n = 1) [ 30 ], preliminary studies ( n = 3) (no control group used) [ 31 , 32 , 33 ], inclusion of plant sterols in the intervention product ( n = 2) [ 34 , 35 ], duplicate publication ( n = 1) [ 36 ], no measure of BP ( n = 1) [ 37 ], insufficient data ( n = 2) [ 38 , 39 ], intervention duration was less than four weeks [ 40 , 41 ], and in Japanese and unable to be translated ( n = 1) [ 42 ]. When the nutritional intervention included LTP and LTP with other intervention (e.g., exercise) [ 43 , 44 ] or substances [ 45 , 46 ] (e.g., other LTP or K + ), only data from LTP supplementation arm and control were used.…”

The impact of milk proteins and peptides on blood pressure and vascular function: a review of evidence from human intervention studies

“…Although there was a significant reduction in AIx at the end of the high-dose treatment compared with baseline (2 1·53 (SD 6·8) %; P¼0·013), there was no significant change in their index of endothelial function. Turpeinen et al (52,53) also failed to report any significant change or differences in arterial stiffness in hypertensive participants in response to the short-and longer-term consumption of a spread containing LTP and plant sterols (short term: 8 h postprandially, n 25, 250 g spread per d (52) ; long term: 10 weeks, n 62, 20 g spread per d) (53) . Nevertheless, significant decreases in SBP (P¼0·026), total serum cholesterol (P¼0·003) and LDL (P¼0·002) were reported in the longer-term intervention, relative to the control.…”

Clinical applications of bioactive milk components

“…120 The supplementation of infant formula with TGF-b is an example of the potential use of bioactive milk components in clinical practice (Table 2). [36][37][38]104,[116][117][118][119][121][122][123][124][125][126][127][128][129][130] …”

“…128 Recently, this result was independently validated in a distinct population. 129 Val-Pro-Pro/IlePro-Pro preparations are remarkably well tolerated at up to 5 times the effective dose. 130 Recent data indicate that human milk casein peptides are generated in vivo, and the analysis and biological characterization of these structures may result in the identification of casein peptides with enhanced activity.…”