The oral assumption of lactotripeptides (LTP) Valine-Proline-Proline (VPP) and Isoleucine-Proline-Proline (IPP) is supposed to improve blood pressure (BP) control by ACE-inhibition. Our group has recently performed a meta-analysis of placebo-controlled clinical trials evaluating the antihypertensive effect of LTP assumed as nutraceuticals or functional foods. Pooled effect of peptides was a reduction of -3.73 mmHg (95%CI: -6.70, -1.76) for systolic BP (SBP), and 1.97 mmHg (95%CI: -3.85, -0.64) for diastolic BP (DBP). The effect was more evident in Asian patients [SBP: -6.93 mmHg (95%CI: -10.95, -2.94); DBP= -3.98 mmHg (95%CI: -5.38, -2.44)] than in Caucasian ones [SBP = -1.17 mmHg (95%CI: -2.82, 0.72); DBP= -0.52 mmHg (95%CI: -1.39, 0.13)], and apparently not related to age, baseline BP values and length of the treatment [1].
Since the most part of available data on Caucasian subjects derived from North-European countries, we carried out a randomized, double-blind, cross-over clinical study to investigate the LTP antihypertensive efficacy in Mediterranean subjects. We consecutively enrolled 55 untreated subjects, with normal or high-normal BP. After 4 weeks of dietary standardization, they were allocated to treatment with a fruit juice containing 3 mg of added LTPor with placebo for 4 weeks. After a 4 week wash-out period, they were then assigned to the alternative treatment for a further period of 4 weeks. A mild but significant reduction in SBP (-1.7±2.3 mmHg, p=0.002) has been observed only in subjects with high-normal BP after treatment with LTP. In regards to 24h BP measurement, after LTP treatment only, the subjects experienced a significant reduction in diurnal DBP (-1.6±5.4 mmHg, p=0.042), in diurnal mean BP (-2.1±5.9 mmHg, p=0.19), in 24-hour (-5.4±14.2 mmHg, p=0.011) and diurnal (-7.1±19.2 %, p=0.014) DBP value measurements over the normal. No modification has been observed in relation to plasma renin activity and aldosteronemia [2].
Finally, to better understand the LTP mechanism of action, we evaluated their effect on a large number of haemodynamic parameters in the context of a double-blind, RCT, carried out on 52 patients affected by high-normal BP or first degree hypertension.In the LTP treated subjects, we observed a significant reduction in office SBP (-5±8 mmHg, p=0.013) and to a significant improvement of pulse wave velocity (-0.66±0.81 m/s, p=0.001) (instrumental biomarker of vascular rigidity). No effect of both treatment has been observed as it regards 24-hour ambulatory BP (ABPM)parameters and BP reaction to stress. LTP, but not placebo, are associated with a mild but significant change in stroke volume and stroke volume index(markers of cardiac flow), acceleration index and velocity index (markers of cardiac contractility). No effect has been observed on parameters related to fluid dynamics or vascular resistance [3].
In conclusion, on the basis of our data, LTP could mildly but significantly improve BP, pulse-wave velocity, stroke volume, stroke volume index, acceleration index and velocity index in patients with normal high BP or first degree hypertension.
 
[1] Cicero et al. (2010) Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials. J Human Hypert [Epub ahead of print]
[2] Cicero et al. (2011) Lactotripeptides effect on office and 24-hour ambulatory blood pressure, blood pressure stress answer, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first degree hypertension: a randomized, double-blind, clinical trial. Hypert Res, In press
[3] Cicero et al. (2010) Haemodynamic effects of Lactotripeptides from casein hydrolysate in Mediterranean normotensive subjects and patients with high-normal blood pressure: a randomized, double-blind, cross-over clinical trial. J Med Food 13(6), 1363-1368