In subjects with stage 1 hypertension, daily intake of MPH1, delivering 15 mg IPP, for 4 weeks lowered systolic BP by 3.8 mm Hg and diastolic BP by 2.3 mm Hg compared with placebo. Daily intake of MPH2 containing 13.2 mg MAP, 4.6 mg LPP, and 3.7 mg IPP did not affect BP in these subjects. Since MPH1 contains primarily IPP while MPH2 contains mainly MAP and LPP, this differential effect despite equal protein dose of the two treatments suggests superiority of IPP over the other peptides for BP lowering, or even functional antagonism of MAP and LPP against IPP (i.e. MAP and LPP having an opposite effect compared to IPP in vivo). Alternatively, MAP and LPP may be less bioavailable than IPP. The bioavailability of IPP has been demonstrated in humans , but bioavailability data for MAP and LPP are lacking.
In our study MPHs were given for a period of 4 weeks. A further lowering of BP might have been achieved in a longer treatment periods as has been shown in studies on comparable products [27–30].
In subjects with prehypertension, daily intake of both MPH1 and MPH2 did not affect BP. Also in other studies, lactotripeptides, in particular VPP and IPP, appear more effective in reducing BP of subjects with a higher starting BP (Sano et al, 2005; Aihara et al, 2005). Indeed, in none of the trials with normotensives were any statistically significant BP changes found [31–34]. This is in line with findings in studies using pharmaceutical interventions .
In many papers, BP reduction through lactotripeptides has been suggested to be due to inhibition of the renin-angiotensin system, which plays an important role in regulating arterial pressure. Renin converts angiotensinogen to the biologically inactive angiotensin I, which in turn undergoes proteolytic cleavage by ACE to the vasoconstrictor angiotensin II . Inhibition of ACE leads to an increase of the angiotensin I/angiotensin II ratio and a subsequent compensatory increase in renin activity. We could not demonstrate any effects of either MPH on renin activity, angiotensin I and II. Although local ACE inhibitory effects near the vascular wall may be overlooked by measuring angiotensin in blood samples from the systemic circulation, these findings do not support an angiotensin-mediated effect of ACE inhibition in vivo. This may explain why the in vitro ACE inhibitory potency of MPH1 and MPH2 did not predict their BP lowering activity. Indeed, based on their IC50 values, MPH2 was expected to lower BP more than MPH1, but the contrary was found in this study.
An alternative way in which ACE inhibition could be involved in the observed BP effects would be through an increased availability of the endogenous vasodilator bradykinin . Alternative mechanisms, such as such as opioid-like activities, inhibition of the release of the vasoactive substances such as the vasoconstrictor endothelin-1, eicosanoids and nitric oxide have been proposed to underlie the blood pressure lowering effect of lactotripeptides (see  for a review). Further work is needed to better characterize these mechanisms.
Since lactotripeptides are frequently taken in a dairy drink or a similar vehicle, it is often unclear whether the blood pressure lowering effects are solely due to the lactotripeptides, or whether minerals in these drinks contribute to the blood pressure lowering effects as well. In the current study, the lactotripeptides have been administered in capsules rather than in dairy drinks. Also, MPH1 contains very few minerals (1.1 mg K+ + Ca2+ per mg IPP) compared to other products that have been administered in capsules in other studies (2.3 - 3.6 mg K+ + Ca2+ per mg IPP) [28, 31, 33, 39]. Therefore, it is very unlikely that minerals have contributed to the observed blood pressure lowering effect.
The doses of MPH used in this study did not exert any significant effects on blood and urine parameters, adverse events, and other adverse effects, and were thus considered safe. Previous studies confirmed that even high daily dosages of VPP and IPP were safe [10, 31, 33, 34, 39].
The BP reductions found for MPH1 are in the order of magnitude of those that can be achieved by lifestyle modifications, such as weight loss in overweight subjects , regular aerobic exercise [41, 42], adjustment of dietary habits , and moderation of alcohol consumption . Cook and co-workers  and Whelton and co-workers  investigated the impact of small reductions in the population distribution of diastolic BP, such as those found in our study and those potentially achieved by lifestyle modification, on incidence of cardiovascular heart disease and stroke. Cook estimated that a 2 mm Hg reduction in the population average of diastolic BP for white US subjects aged 35-64 y would result in a 17% decrease in the prevalence of hypertension, a 15% reduction in the risk of stroke, and a 6% reduction in the risk of coronary heart disease.