THE SHORT VERSION

  • In a 2010 trial, the preparation that blocked an enzyme more strongly in the lab did not significantly lower blood pressure. The other preparation did, in a subgroup of 26 people with higher readings.
  • Human results are mixed. Some milk-protein preparations produced small reductions after weeks of use. Other trials found no clear benefit.
  • The takeaway: a laboratory result alone cannot establish a blood-pressure benefit in people.
  • The question to ask: which preparation and dose were tested, in whom, and what actually changed?

In a 2010 trial, researchers compared two milk-protein preparations with placebo, a capsule without the active ingredient. Both preparations were hydrolysates: proteins that enzymes had already cut into smaller pieces called peptides.1

One preparation blocked a blood-pressure-related enzyme more strongly in laboratory testing. Yet in people, only the other preparation lowered blood pressure, and only in the group with higher readings.1

The result separates two questions: can a preparation block an enzyme in a laboratory, and does taking it change a person’s blood pressure? The first finding cannot answer the second.

Why three amino acids attracted attention

ACE stands for angiotensin-converting enzyme. It helps the body make angiotensin II, a molecule that narrows blood vessels. Blocking this step is one possible way to lower blood pressure.1

In 1995, researchers isolated two ACE-blocking peptides from fermented milk: isoleucine-proline-proline, or IPP, and valine-proline-proline, or VPP. Each consists of three amino acids joined together. That makes them tripeptides; together, these milk-derived fragments are often called lactotripeptides.2,3

The sequences occur within casein. Enzymes can release them as the protein is broken apart. Fermentation and controlled enzyme treatment can produce preparations containing these fragments before anyone consumes them.2,3

Those preparations can be tested for enzyme inhibition in the lab. A blood-pressure effect after consumption needs evidence in people.1

What changed when the preparations reached people

The 2010 trial used a randomized, double-blind crossover design. Each person received every treatment in turn, in a randomly assigned order. Participants and researchers did not know which capsules were being taken during each period.1

Researchers enrolled 80 adults and analyzed blood-pressure effects in 70. They grouped people using readings during the placebo period; 10 whose readings were then normal were excluded. Of the remaining 70, 26 were classified as having stage 1 hypertension and 44 as having prehypertension, using the definitions in use at the time.1

Participants took each preparation or placebo for four weeks. One preparation supplied 15 milligrams of IPP daily. The other supplied a different peptide mixture, including about 3.7 milligrams of IPP.1

In the subgroup of 26 people with stage 1 hypertension, the IPP-rich preparation lowered systolic pressure, the upper number, by 3.8 mmHg compared with placebo. Diastolic pressure, the lower number, fell by 2.3 mmHg. The unit mmHg means millimeters of mercury.1

The same preparation did not significantly lower pressure in people with milder elevations. The other preparation showed no significant benefit in either group, despite being the somewhat stronger ACE inhibitor in the laboratory.1

Blood markers of the hormone system that includes ACE did not differ from placebo either. They therefore did not confirm that ACE inhibition explained the drop. The study showed a blood-pressure change in one subgroup, while leaving the mechanism unresolved.1

Results versus placebo in the 26-person subgroup from the 2010 trial. Stage labels follow that study’s definitions. Blood tests did not confirm ACE inhibition as the explanation.1

Results versus placebo in the 26-person subgroup from the 2010 trial. Stage labels follow that study’s definitions. Blood tests did not confirm ACE inhibition as the explanation.1

A separate 2015 trial analyzed 104 adults with metabolic syndrome, a cluster of risk factors that can include high blood sugar and excess fat around the waist. For 12 weeks, participants received fermented milk supplying either 5 or 25 milligrams of lactotripeptides daily, along with 2 grams of plant sterol esters, or placebo.4

Neither active preparation lowered blood pressure compared with placebo, whether measured at home or in the laboratory. Measures of resistance in blood vessels and the heart’s pumping output also showed no treatment advantage.4

An earlier, 2008 trial of 135 Dutch adults with raised systolic pressure tested drinks containing 14 milligrams a day of IPP and VPP, made in three different ways. None significantly lowered blood pressure compared with placebo after eight weeks.5

These trials tested different preparations in different groups of people. The peptide’s name alone does not tell you whether a particular formulation will lower blood pressure.1,4,5

What pooling the trials shows

A meta-analysis combines results from several trials to estimate an average effect. A 2011 analysis of 18 placebo-controlled lactotripeptide trials found average reductions of 3.7 mmHg in systolic pressure and 2.0 mmHg in diastolic pressure.6

The systolic reduction was larger in trials involving Asian participants, at 6.9 mmHg, and smaller and not statistically significant in those involving White participants, at 1.2 mmHg. Those differences between study groups do not, by themselves, explain why the results differed.6

A 2012 Cochrane review of fermented milk included 15 studies and 1,232 participants. It found an average systolic reduction of about 2.5 mmHg and no clear diastolic effect. The authors judged the evidence insufficient to support using fermented milk to lower blood pressure.7

Their reasons matter: the systolic change was small, the studies varied widely, and several had weak methods. The benefit also did not hold up in additional analyses. A favorable average can therefore sit alongside substantial uncertainty about how reliable it is.7

Whey has been tested in a different form

Researchers have also studied intact whey protein, rather than preparations enriched with particular casein peptides. In the 2016 Whey2Go crossover trial, 42 adults with mildly raised blood pressure were randomized and 38 completed all three treatment periods.8

Each period lasted eight weeks, with four-week breaks between them. Participants took whey protein isolate, calcium caseinate, a form of casein, or maltodextrin, a carbohydrate control. Each protein supplement was given as two 28-gram portions of powder daily, totaling 56 grams of supplement.8

The researchers reported average reductions in 24-hour blood pressure of 3.9 mmHg systolic and 2.5 mmHg diastolic with whey compared with control. Both results were at the usual cutoff for statistical significance, with a P value of 0.050, so they warrant cautious interpretation.8

Other measurements showed larger systolic reductions: about 5.7 mmHg in pressure measured away from the heart and 5.4 mmHg in estimated pressure near the heart. Calcium caseinate did not significantly lower blood pressure in this trial.8

These were average changes after weeks of repeated consumption. The amount of supplement and the choice of a carbohydrate control help define what the result means. The trial did not identify a particular peptide as the cause or establish the same response to another dose or finished drink.8

A broader review published in 2025 included 21 randomized trials of whey and heart and metabolic health. Twelve contributed to its blood-pressure analysis, which found no statistically significant overall reduction in either the upper or lower number.9

What a blood pressure finding can tell you

For a peptide to act, enough of it must remain available after digestion and reach the place where it works. A laboratory enzyme test skips much of that journey. Even when blood pressure falls in a trial, the reason can remain uncertain.1,3

Human trials have found small reductions with some milk-protein preparations and no significant benefit with others. The preparation, dose and people studied define how far each result applies. An average change also cannot predict one person’s response.1,4,8,9

Related reading

References

Educational content. The Fountain is written to explain, not to make health claims about any product. This article summarizes published peer-reviewed research. Nothing here is medical advice.

  1. Boelsma E, Kloek J. IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial. Nutrition Journal. 2010;9:52. https://doi.org/10.1186/1475-2891-9-52
  2. Nakamura Y, Yamamoto N, Sakai K, Okubo A, Yamazaki S, Takano T. Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. Journal of Dairy Science. 1995;78(4):777–783. https://doi.org/10.3168/jds.S0022-0302(95)76689-9
  3. Auestad N, Layman DK. Dairy bioactive proteins and peptides: a narrative review. Nutrition Reviews. 2021;79(Suppl 2):36–47. https://doi.org/10.1093/nutrit/nuab097
  4. Hautaniemi EJ, Tikkakoski AJ, Tahvanainen A, et al. Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome: a randomised, double-blind, placebo-controlled study. British Journal of Nutrition. 2015;114(3):376–386. https://doi.org/10.1017/S0007114515002032
  5. Engberink MF, Schouten EG, Kok FJ, et al. Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial. Hypertension. 2008;51(2):399–405. https://doi.org/10.1161/HYPERTENSIONAHA.107.098988
  6. Cicero AFG, Gerocarni B, Laghi L, Borghi C. Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials. Journal of Human Hypertension. 2011;25(7):425–436. https://doi.org/10.1038/jhh.2010.85
  7. Usinger L, Reimer C, Ibsen H. Fermented milk for hypertension. Cochrane Database of Systematic Reviews. 2012;(4):CD008118. https://doi.org/10.1002/14651858.CD008118.pub2
  8. Fekete ÁA, Giromini C, Chatzidiakou Y, Givens DI, Lovegrove JA. Whey protein lowers blood pressure and improves endothelial function and lipid biomarkers in adults with prehypertension and mild hypertension: results from the chronic Whey2Go randomized controlled trial. American Journal of Clinical Nutrition. 2016;104(6):1534–1544. https://doi.org/10.3945/ajcn.116.137919
  9. Prokopidis K, Morgan PT, Veronese N, et al. The effects of whey protein supplementation on indices of cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition. 2025;44:109–121. https://doi.org/10.1016/j.clnu.2024.12.003