Casein-derived peptides VPP and IPP reduced systolic blood pressure by up to 10.1 mmHg in a dose-dependent manner over 6 weeks — a clinically meaningful effect from a food-derived supplement.
−10.1 mmHg systolic BP at highest doseThe 3.6 mg dose of milk-derived peptides VPP+IPP reduced systolic blood pressure by 10 mmHg over 6 weeks — significantly more than placebo (p<0.001) and comparable to some prescription BP drugs
What the researchers found
Milk-derived peptides VPP and IPP — natural ACE inhibitors from casein — lowered systolic blood pressure in a dose-dependent manner over 6 weeks. The highest dose (3.6 mg VPP+IPP daily) produced a 10.1 mmHg decrease in systolic blood pressure, significantly better than placebo (p<0.001). Even the lowest active dose (1.8 mg) produced a significant 6.3 mmHg reduction at 6 weeks.
The blood pressure changes were: placebo −1.7 mmHg, 1.8 mg −6.3 mmHg, 2.5 mg −6.7 mmHg, and 3.6 mg −10.1 mmHg. The effect was stronger in mildly hypertensive subjects. Diastolic blood pressure was not significantly affected.
Why it matters
A 10 mmHg reduction in systolic blood pressure from a food-derived peptide is clinically meaningful — comparable to some blood pressure medications. These lactotripeptides (VPP and IPP) work by the same mechanism as ACE inhibitor drugs (enalapril, lisinopril) but come from fermented milk protein. This study helped establish the scientific basis for functional food products marketed for blood pressure management.
The numbers in context
n=131 · 4 dose groups (0, 1.8, 2.5, 3.6 mg VPP+IPP) · 6-week treatment · SBP reductions: −1.7, −6.3, −6.7, −10.1 mmHg · 3.6 mg vs placebo p<0.001 · dose-dependent response
How the study worked
Single-blind, placebo-controlled trial. 131 volunteers with high-normal blood pressure or mild hypertension were randomized to four groups of 32–33 people. Each received two tablets daily containing either placebo or one of three doses of casein hydrolysate (VPP+IPP at 1.8, 2.5, or 3.6 mg). Blood pressure was measured at baseline, 3 weeks, and 6 weeks. The casein hydrolysate was prepared using Aspergillus oryzae protease.
Who was studied
Adults with high-normal blood pressure or mild hypertension (131 volunteers)
What this study cannot tell us
Single-blind design (only participants blinded, not researchers) introduces potential bias. Relatively small groups (32–33 per arm). Only systolic BP was affected — no diastolic reduction. The 6-week duration doesn't capture long-term effects or safety. The study doesn't compare to standard antihypertensive medications. Japanese study population may limit generalizability.
How to read the evidence
This is a placebo-controlled RCT with dose-response data, which is a strong design. However, it's single-blind rather than double-blind, has relatively small group sizes (32–33 per arm), and comes from a single center. The dose-dependent response strengthens the evidence for a real effect.
When this study was published
Published in 2005. This was an important early trial establishing the blood pressure effects of lactotripeptides. Subsequent meta-analyses have confirmed modest but significant effects. The science remains relevant, though the magnitude of effect has been debated.
The bigger picture
This study is part of a body of research that led to the commercialization of VPP/IPP-containing functional foods and supplements for blood pressure management, particularly popular in Japan and Europe. The lactotripeptides have been the subject of meta-analyses and regulatory reviews. While the effects are modest compared to prescription drugs, they represent a bridge between dietary intervention and pharmacotherapy for people with borderline high blood pressure.
Questions still open
- Can casein-derived peptides serve as a first-line intervention for borderline hypertension before prescribing medications?
- Why was diastolic blood pressure unaffected — does the peptide's ACE inhibition work differently from pharmaceutical ACE inhibitors?
- Are the blood pressure effects sustained with long-term use, or do they plateau or diminish over time?
Common questions
How do milk peptides lower blood pressure?
Is a 10 mmHg blood pressure reduction from food peptides clinically meaningful?
Read the original research
Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension.
The British journal of nutrition, 94(1), 84-91
Citation
Mizuno, Seiichi; Matsuura, Keiichi; Gotou, Takanobu; Nishimura, Shingo; Kajimoto, Osami; Yabune, Mitsuharu; Kajimoto, Yoshitaka; Yamamoto, Naoyuki. (2005). Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension.. The British journal of nutrition, 94(1), 84-91.