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Isoleucine-Proline-Proline (IPP) and Valine-Proline-Proline (VPP) from casein hydrolysate

Lactotripeptides

Research reviewed: Up until 03/2026

Lactotripeptides (Isoleucine-Proline-Proline (IPP) and Valine-Proline-Proline (VPP) from casein hydrolysate) is a dietary supplement with 8 published peer-reviewed studies involving 1,549 participants, researched for Blood Pressure Reduction via ACE Inhibition, Endothelial Function & Vascular Health.

8
Studies
1,549
Participants
2000–2021
Research Span

Evidence at a Glance

Strength is scored by study design, sample size, study type, and outcomes

Overall: Strong Evidence

Blood Pressure Reduction via ACE Inhibition

Strong
4 studies 4 of 4 positive 1,371 participants 3 human

Endothelial Function & Vascular Health

Moderate
4 studies 1 of 4 positive 178 participants 2 human

Research Visualised

Visual breakdown of the clinical data.

Study Quality Breakdown

What types of studies were conducted

5/8
Randomised
5/8
Double-Blind
5/8
Placebo-Controlled

Participants Per Study

Larger samples = more reliable results

Study 1 (2005)
70
Study 2 (2012)
1,200
Study 3 (2000)
39
Study 4 (2005)
62
Study 1 (2009)
68
Study 2 (2014)
0
Study 3 (2011)
110
Study 4 (2021)
0

Research Timeline

When the studies were published

1
2000
2
2005
1
2009
1
2011
1
2012
1
2014
1
2021

All Studies

Detailed breakdown of each trial. Click to expand.

Blood Pressure Reduction via ACE Inhibition

1

To assess the antihypertensive efficacy of fermented milk containing tripeptides IPP and VPP in mildly hypertensive patients.

2005 70 participants 8 weeks 3 × 150 mL/day fermented milk (providing ~5 mg IPP+VPP)
Human Study RCT Double-Blind Placebo Positive

Study Type

Randomised, double-blind, placebo-controlled

Purpose

To assess the antihypertensive efficacy of fermented milk containing tripeptides IPP and VPP in mildly hypertensive patients.

Dose

3 × 150 mL/day fermented milk (providing ~5 mg IPP+VPP)

Participants

70 mildly hypertensive adults

Duration

8 weeks

Results

Fermented milk containing IPP and VPP significantly reduced SBP (−4.8 mmHg) and DBP (−2.2 mmHg) vs control milk. ACE inhibitory activity was confirmed ex vivo. The magnitude of effect was clinically meaningful for mild-to-moderate hypertension management.

How They Measured It

Clinic and 24-hour ambulatory SBP and DBP

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2

To meta-analyse the blood pressure-lowering effects of casein-derived lactotripeptides (IPP, VPP) across human RCTs.

2012 1,200 participants 4–12 weeks Various (2–10 mg IPP+VPP/day)
Review/Other Positive

Study Type

Systematic review and meta-analysis

Purpose

To meta-analyse the blood pressure-lowering effects of casein-derived lactotripeptides (IPP, VPP) across human RCTs.

Dose

Various (2–10 mg IPP+VPP/day)

Participants

Multiple RCTs (>1,200 participants)

Duration

4–12 weeks

Results

Lactotripeptides significantly reduced SBP (WMD −2.95 mmHg) and DBP (WMD −1.51 mmHg) vs placebo. Effects were consistent across populations and dairy matrices. Greater reductions were observed in hypertensive compared to normotensive subjects.

How They Measured It

Pooled SBP and DBP from all eligible RCTs; subgroup analysis by baseline BP, population, and dose

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3

To evaluate the antihypertensive effects of sour milk (Lactobacillus helveticus-fermented) containing IPP and VPP.

2000 39 participants 8 weeks 150 mL/day fermented sour milk (IPP+VPP producing Lactobacil...
Human Study RCT Double-Blind Placebo Positive

Study Type

Randomised, double-blind, placebo-controlled

Purpose

To evaluate the antihypertensive effects of sour milk (Lactobacillus helveticus-fermented) containing IPP and VPP.

Dose

150 mL/day fermented sour milk (IPP+VPP producing Lactobacillus helveticus)

Participants

39 mildly hypertensive patients

Duration

8 weeks

Results

Sour milk significantly reduced SBP by −6.7 mmHg and DBP by −3.6 mmHg. ACE activity was significantly inhibited. Plasma renin activity increased (consistent with ACE inhibition). This pioneering Finnish trial confirmed the antihypertensive mechanism of lactotripeptides.

How They Measured It

Clinic blood pressure, ACE activity, plasma renin activity

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4

To assess lactotripeptide (IPP, VPP) tablets on blood pressure in Japanese hypertensive adults.

2005 62 participants 8 weeks Lactotripeptide tablet equivalent to 3.4 mg IPP + 3.6 mg VPP...
Human Study RCT Double-Blind Placebo Positive

Study Type

Randomised, double-blind, placebo-controlled

Purpose

To assess lactotripeptide (IPP, VPP) tablets on blood pressure in Japanese hypertensive adults.

Dose

Lactotripeptide tablet equivalent to 3.4 mg IPP + 3.6 mg VPP daily

Participants

62 hypertensive Japanese adults

Duration

8 weeks

Results

Lactotripeptide tablets significantly reduced home SBP (−5.2 mmHg) and DBP (−2.9 mmHg) vs placebo. Office blood pressure was also reduced. No adverse events were reported. Results confirm the antihypertensive benefit of lactotripeptide tablets as a practical supplement form.

How They Measured It

Home and office SBP and DBP, adverse events

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Endothelial Function & Vascular Health

1

To evaluate lactotripeptides on endothelial function and arterial stiffness.

2009 68 participants 8 weeks 5 mg/day IPP+VPP
Human Study RCT Double-Blind Placebo Positive

Study Type

Randomised, double-blind, placebo-controlled

Purpose

To evaluate lactotripeptides on endothelial function and arterial stiffness.

Dose

5 mg/day IPP+VPP

Participants

68 adults with pre-hypertension

Duration

8 weeks

Results

Lactotripeptides significantly improved FMD (+1.9%) and reduced arterial stiffness (pulse wave velocity −0.4 m/s). Blood pressure was meaningfully reduced (SBP −4.1 mmHg). The improvement in vascular function precedes and may mediate longer-term blood pressure benefits.

How They Measured It

FMD, pulse wave velocity, reactive hyperaemia index, blood pressure

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2

To comprehensively review the molecular mechanisms and clinical evidence for dairy-derived peptides in blood pressure control.

2014 ? participants Various Various fermented dairy products and purified lactotripeptid...
Review/Other Mixed

Study Type

Review — mechanisms and clinical data

Purpose

To comprehensively review the molecular mechanisms and clinical evidence for dairy-derived peptides in blood pressure control.

Dose

Various fermented dairy products and purified lactotripeptides

Participants

Multiple studies reviewed

Duration

Various

Results

IPP and VPP are potent ACE inhibitors (IC50 in μM range). Human trials consistently show 3–8 mmHg SBP reductions. Mechanisms also include reduced endothelin-1, improved NO bioavailability, and direct vasodilatory effects. Lactotripeptides are among the best-evidenced dietary bioactive peptides for blood pressure management.

How They Measured It

Synthesis of in vitro ACE inhibition studies, animal models, and human RCTs

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3

To evaluate lactotripeptide-containing drink on blood pressure in subjects with metabolic syndrome.

2011 110 participants 12 weeks 250 mL/day functional drink containing 5.1 mg IPP+VPP
Human Study RCT Double-Blind Placebo Positive

Study Type

Randomised, double-blind, placebo-controlled

Purpose

To evaluate lactotripeptide-containing drink on blood pressure in subjects with metabolic syndrome.

Dose

250 mL/day functional drink containing 5.1 mg IPP+VPP

Participants

110 adults with metabolic syndrome

Duration

12 weeks

Results

The lactotripeptide drink significantly reduced 24-hour ambulatory SBP (−5.3 mmHg) and DBP (−2.9 mmHg). Waist circumference and fasting glucose trends improved but were not statistically significant. Blood pressure benefits were consistent with those from other lactotripeptide studies.

How They Measured It

24-hour ambulatory blood pressure, waist circumference, fasting glucose, lipid panel

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4

To update the meta-analysis of lactotripeptide (IPP, VPP) effects on blood pressure with more recent RCT data.

2021 ? participants 4–12 weeks Various lactotripeptide preparations
Review/Other Positive

Study Type

Updated systematic review and meta-analysis

Purpose

To update the meta-analysis of lactotripeptide (IPP, VPP) effects on blood pressure with more recent RCT data.

Dose

Various lactotripeptide preparations

Participants

Updated pooling of multiple RCTs

Duration

4–12 weeks

Results

Updated meta-analysis confirmed significant SBP and DBP reductions with lactotripeptides. Effect sizes were modest but clinically relevant, particularly for pre-hypertension management as a non-pharmacological approach. No significant publication bias was detected.

How They Measured It

Pooled SBP and DBP across updated RCTs; publication bias assessment

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Frequently Asked Questions

Common questions about Lactotripeptides research

What does the research say about Lactotripeptides?

There are currently 8 peer-reviewed studies on Lactotripeptides (Isoleucine-Proline-Proline (IPP) and Valine-Proline-Proline (VPP) from casein hydrolysate), involving 1,549 total participants. Research covers Blood pressure reduction, ACE inhibition, Endothelial function and 1 more areas. The overall evidence strength is rated as Strong.

How strong is the evidence for Lactotripeptides?

The evidence is currently rated as "Strong Evidence". This rating is based on study design quality (randomisation, blinding, placebo controls), sample sizes, study types (5 human studies), and reported outcomes.

What health goals has Lactotripeptides been studied for?

Lactotripeptides has been researched for: Blood pressure reduction, ACE inhibition, Endothelial function, Vascular health. Each area has its own body of evidence which you can explore in the study breakdowns above.

Are the studies on Lactotripeptides based on human trials?

Yes, 5 out of 8 studies are human trials. Human trials carry more weight in our evidence scoring system.