Supplement
Lactotripeptides (IPP and VPP)
Also known as IPP · VPP · IPP and VPP · Ile-Pro-Pro · Val-Pro-Pro · isoleucine-proline-proline · valine-proline-proline · isoleucyl-prolyl-proline · valyl-prolyl-proline · L-isoleucyl-L-prolyl-L-proline · L-valyl-L-prolyl-L-proline · lactotripeptide · lacto-tripeptides · lacto tripeptides · LTP · LTPs · milk tripeptides · casein-derived tripeptides · casein tripeptides · milk-derived ACE-inhibitory peptides · antihypertensive milk peptides · fermented milk peptides · AmealPeptide · Ameal · Ameal S · Calpis sour milk · Evolus · beta-casein f(74-76) · beta-casein f(84-86) · bioactive tripeptides
Tested in people, but barely
23 of 55 peptides sit at this level
- Category
- Supplement
- Doping status
- Not banned in sport
- Sources
- 27
Lactotripeptides are two very short peptides from milk protein — isoleucine-proline-proline and valine-proline-proline, usually shortened to IPP and VPP — made by fermenting milk with bacteria or by cutting casein up with enzymes, and sold in drinks and capsules for blood pressure. Around thirty randomised trials have compared them against a dummy drink, and when those trials are pooled the average blood pressure difference is a couple of millimetres of mercury, which is smaller than the difference between two readings taken minutes apart. The European Food Safety Authority assessed exactly this claim twice and concluded both times that a cause and effect relationship has not been established; the European Commission then refused the claim in law in 2013. The clearest single pattern in the data is not about the peptide at all: trials run in Japan report roughly four times the effect of trials run in Europe, and nobody has shown why.
Lactotripeptides (IPP and VPP)What it is
What it is
Not one peptide but two, each three amino acids long: isoleucine-proline-proline and valine-proline-proline, almost always written IPP and VPP. Both sit inside beta-casein, the main protein in cow's milk — IPP at positions 74 to 76 of the mature protein and VPP at 84 to 86 — and both are released when that protein is broken down, either by fermenting milk with Lactobacillus helveticus or by cutting casein with enzymes. They are sold together, in fermented milk drinks and in capsules, for blood pressure. PubChem gives IPP as C16H27N3O4 (325.40 g/mol, CID 9949212) and VPP as C15H25N3O4 (311.38 g/mol, CID 9818200). The sequence field is deliberately empty: this record covers two different molecules, and a single one-letter code cannot describe both. Written separately they are IPP and VPP.
How it is sold, and whether it is legal
- Sold as
- Swallowed — fermented milk drinks, or capsules and tablets of a milk-protein hydrolysate.
- Legal status in the EU
- A food and food supplement in the EU, not a medicine, sold in fermented milk drinks and in capsules. There is no authorised health claim about blood pressure. The European Food Safety Authority concluded in 2011 (EFSA Journal 2011;9(9):2380, on an application from Valio Ltd via the Finnish authority) and again in 2012 (EFSA Journal 2012;10(6):2715, at the European Commission's request) that a cause and effect relationship has not been established between the consumption of IPP and VPP and maintenance of normal blood pressure. On 23 October 2013 the European Commission refused to authorise the wording "Peptides IPP and VPP help to maintain normal blood pressure" in Commission Regulation (EU) No 1017/2013. The products remain legal to sell as food; the claim on the packet does not.
What it does in your body
7 parts of the body · 1 measured in people, 1 where studies in people disagree, 3 from one small study, 1 only seen in animals, 1 only seen in a dish
The proposed mechanism is that the two peptides block angiotensin-converting enzyme, the same enzyme a common class of blood pressure tablets blocks. They do block it in a test tube: the concentrations that halve its activity are 5 micromoles per litre for IPP and 9 for VPP, and 2024 crystal work shows where they bind. The arithmetic does not carry over into a person. After a lactotripeptide drink, peak IPP in the blood was 897 picomoles per litre against 555 after a dummy drink — roughly five thousand times below the concentration that half-blocks the enzyme in a dish — and a later review put the absorbed fraction at about 0.1 per cent. When the mechanism was tested directly in 135 people over 8 weeks, enzyme activity in the blood and angiotensin II were both unchanged relative to the dummy drink. In rats, cutting the vagus nerve abolished the peptides' effect while a conventional ACE-blocking drug kept working, which points away from the enzyme story rather than towards it. Among the European Food Safety Authority's stated reasons for concluding against the claim was that no convincing evidence for a mechanism at the proposed dose had been provided.
- The same enzyme, measured in people after weeks of drinking it
- If the peptides worked by blocking that enzyme, the enzyme's activity in the blood should fall. It was measured, in the trial designed to check it. It did not fall relative to the dummy drink, and neither did angiotensin II, the substance the enzyme produces. That is a direct test of the proposed mechanism in a person, and it came back negative.
- One randomised double-blind trial in 135 Dutch adults with raised blood pressure and no blood pressure medication, given 14 mg of lactotripeptides a day in a 200 ml dairy drink for 8 weeks against a dummy drink. Enzyme activity and angiotensin II were pre-specified secondary measurements; the paper reports that treatment had no significant effect on any of them.
- Measured in people
- Source [06]
- Blood pressure
- This is the only thing these peptides are really sold for, and it is the thing that has been measured most and settled least. Pooling every randomised trial against a dummy drink gives a small average fall in the top blood pressure number. Pooling only the trials that used a monitor worn for a full day, rather than a single reading in a clinic, gives no clear difference at all. The Cochrane reviewers who looked at the same field concluded that the evidence does not support an effect, on the grounds that what was found was very modest, appeared in only one of the two numbers, and came from trials that were very heterogeneous and several of which had weak methods.
- Pooled from 30 randomised placebo-controlled trials, yielding 33 sets of data, searched to May 2014. Separately pooled by Cochrane reviewers from 15 randomised trials in 1,232 people. The two pooled analyses reach opposite verdicts on the same kind of data, which is why this line is graded as studies in people disagreeing rather than as a measured effect.
- Studies in people disagree
- Source [04]Source [05]
- Blood, in the hours after you drink it
- Almost all of a swallowed peptide is destroyed in the gut. These two are unusual in that a trace of one of them survives: after a lactotripeptide yogurt drink, the amount of IPP in the blood roughly doubles compared with the same drink without it. The word to hold on to is trace. The peak concentration measured is around 900 picomoles per litre, which is about a thousandth of a millionth of a mole in a litre of blood, and a later review put the fraction of the swallowed dose that gets there at roughly one part in a thousand. The dummy drink itself produced a measurable IPP level, because milk protein in ordinary food releases small amounts of it anyway.
- A placebo-controlled crossover study in 6 healthy men and women, each drinking a lactotripeptide-enriched yogurt beverage or a dummy on separate occasions, with blood sampled afterwards. Peak IPP was 897 picomoles per litre after the lactotripeptide drink against 555 after the dummy, and the total exposure over time was 2.1 times higher. Eating a meal first raised total exposure a further 1.3 times by slowing the peptide's clearance.
- One small study
- Source [10]Source [11]
- Artery stiffness and the lining of the blood vessels
- A second story sold about these peptides is that they make arteries more supple, separately from the blood pressure number. The Japanese crossover trial that tested it measured how well the artery in the arm widens when blood flow is released, and measured how fast the pulse travels from the arm to the ankle, which is the stiffness reading used most in Japan. Neither differed from the dummy drink. A 54-person American trial in people with coronary artery disease was registered to measure the same thing, finished in May 2012, and has posted no results.
- A randomised double-blind crossover in 26 Japanese adults with blood pressure just above normal, 8 weeks on each of the peptide drink and the dummy with a 4-week gap. The registered American trial is NCT00924157, run by Boston University, 54 participants, completed May 2012, no results posted as of 4 August 2026.
- One small study
- Source [14]Source [15]
- The kidneys
- In the same 26-person Japanese crossover, one marker of kidney stress in the urine came out lower after the peptide period than after the dummy period. The authors read that as a protective effect on the kidney. It is one marker, in 26 people, in a study funded by the company that sells the peptide, and it was not the study's main question. Nothing has followed anyone long enough to see whether kidney function itself differs.
- 26 adults, crossover, 8 weeks per period. Urinary liver-type fatty acid-binding protein relative to creatinine was 1.85 after the peptide against 2.37 after the dummy (P = 0.02).
- One small study
- Source [14]
- Blood pressure in rats
- In rats bred to develop high blood pressure, a single dose of either peptide lowered blood pressure for a few hours, and the same doses did nothing in rats with normal blood pressure. Later work complicates the enzyme explanation rather than supporting it: when the vagus nerve, the nerve running from the gut to the brain, was cut, both peptides stopped working, while a standard ACE-blocking tablet kept working. The peptides also only worked when put into the stomach, not when put straight into the intestine. That points at a signal starting in the gut wall rather than at an enzyme being blocked in the bloodstream.
- The original 1995 rat work used single oral doses in spontaneously hypertensive rats and in normal rats. The nerve work is a 2017 anaesthetised-rat study with nerve recordings and surgical cutting of the vagus nerve. Neither is a person.
- Only seen in animals
- Source [16]Source [17]
- The enzyme that raises blood pressure, in a test tube
- The whole story starts here. Angiotensin-converting enzyme, usually shortened to ACE, is the enzyme that a common class of blood pressure tablets blocks. Both peptides block it in a dish. The amount needed to block half of it is 5 micromoles per litre for IPP and 9 for VPP. Crystal work published in 2024 showed where they sit on the enzyme and that they prefer one of its two halves. The problem is arithmetic, not chemistry: the peak level measured in a person's blood after a lactotripeptide drink is roughly five thousand times lower than the amount that half-blocks the enzyme in a dish. This is the gap the food safety authority pointed at when it said there was no convincing evidence for a mechanism at the dose being proposed.
- The blocking concentrations come from the original 1995 purification of the two peptides out of Calpis sour milk, where they accounted for most of the milk's enzyme-blocking activity. The structural work is X-ray crystallography with kinetic measurements, done on purified human enzyme, not in a person.
- Only seen in a dish, not in a body
- Source [08]Source [10]Source [12]
What changed when it was measured
10 findings · 3 measured in people, 4 where studies in people disagree, 3 from one small study
This claim was formally tested by a regulator and it failed. The European Food Safety Authority assessed "peptides IPP and VPP help to maintain normal blood pressure" twice — once at the European Commission's request and once on an application from the Finnish dairy Valio — and concluded both times, in the same words, that a cause and effect relationship has not been established; the Commission then refused the claim in law in Commission Regulation (EU) No 1017/2013. The two largest European trials found nothing against their own control arms: in 275 Dutch adults, 10.2 mg a day for 8 weeks gave p = 0.66 for the top blood pressure number and p = 0.72 for the bottom, and in 135 Dutch adults three different preparations differed from the dummy drink by 2.8 mmHg higher, 0.5 lower and 1.6 higher, every confidence interval including no difference. Pooling roughly thirty randomised placebo-controlled trials does give a small average difference — 2.95 mmHg on the top number (95 per cent confidence interval 4.17 to 1.73 lower) — but the same analysis found the day-long monitor measurement non-significant (p = 0.101) and identified both publication bias and a small-study effect. The Cochrane reviewers who pooled 15 trials in 1,232 people concluded the review does not support an effect, and recorded that every included trial but one was funded by a company with a financial interest in the product. The evidence also splits by geography in a way nobody has explained: 5.54 mmHg lower than a dummy drink across 16 trials run in Japan, against 1.36 mmHg across 16 trials run in Europe, a difference that is itself statistically significant (p = 0.002).
One of the two peptides is measurable in the blood within hours of drinking it, and eating a meal first makes it stay there slightly longer. Everything after that is measured in weeks. The trials that have been pooled ran from 2 to 21 weeks and averaged 7.8 weeks, and the pooled analysis found no relationship between how long the treatment lasted and how large the difference was: trials of 8 weeks or less differed from longer ones by p = 0.966 on the top blood pressure number and p = 0.921 on the bottom one. Twenty-one weeks is the longest anyone has been followed in a published randomised trial of these peptides, and no trial has ever run long enough to count a heart attack or a stroke.
- Blood pressure in the largest single European trial
- No reduction against the dummy drink: p = 0.66 for the top number and p = 0.72 for the bottom one. The authors describe their own result as showing no effect in a fairly large study.
- 275 Dutch adults with mildly raised blood pressure, 10.2 mg a day of enzyme-made lactotripeptides in a yogurt drink for 8 weeks, against a dummy drink
- Measured in people
- Source [07]
- Blood pressure in the trial that tested three different ways of making the peptides
- All three lost to the dummy drink or drew with it. Against the dummy, the difference in the top number was 2.8 mmHg higher for peptides made by concentrating fermented milk (interval 2.6 lower to 8.2 higher), 0.5 mmHg lower for peptides made with enzymes (6.0 lower to 5.0 higher) and 1.6 mmHg higher for chemically synthesised peptides (3.9 lower to 6.9 higher). Every interval includes no difference. Blood pressure at the start averaged 142 over 84.
- 135 Dutch adults with a raised top number and no blood pressure medication, 14 mg a day for 8 weeks after a 2-week run-in on the dummy drink
- Measured in people
- Source [06]
- Day-long blood pressure in two European crossover trials
- No significant difference between the peptide period and the dummy period in either study (p above 0.10 in both). Blood pressure measured in the clinic did fall by more than 5 mmHg over the course of both studies — but it fell on the dummy drink too, and the difference between the two was not significant. The authors' summary is that the data do not support a blood-pressure-lowering effect in white participants.
- 69 adults in one study and 93 in the other, each spending 4 weeks on the peptide drink and 4 weeks on the dummy with a 4-week gap between
- Measured in people
- Source [20]
- The top blood pressure number, measured in a clinic, everything pooled
- 2.95 mmHg lower than on a dummy drink (95% confidence interval 4.17 to 1.73 lower). The bottom number was 1.51 mmHg lower (2.21 to 0.80). For scale, a normal blood pressure reading moves by more than that between one measurement and the next in the same person. The same authors report that both publication bias and a small-study effect were present, and that correcting for them shifted the result towards a smaller top-number difference and no difference at all in the bottom number.
- 30 randomised placebo-controlled trials, 33 sets of data, in adults, searched to May 2014
- Studies in people disagree
- Source [04]
- The same number, split by where the trial was run
- In 16 trials run in Japan, 5.54 mmHg lower than on a dummy drink (95% confidence interval 7.43 to 3.65 lower). In 16 trials run in Europe, 1.36 mmHg lower (2.53 to 0.20 lower). The gap between those two groups of trials is itself statistically significant (p = 0.002 for the top number, below 0.001 for the bottom one). An earlier pooled analysis found the same shape more starkly: 6.93 mmHg lower in Asian participants (10.95 to 2.94 lower) against 1.17 mmHg in white participants, where the interval ran from 2.82 lower to 0.72 higher and therefore included no difference at all.
- The 30-trial pooled analysis split by country of the trial, and an earlier 18-trial pooled analysis split by the ethnicity of the participants
- Studies in people disagree
- Source [04]Source [18]
- Blood pressure measured by a monitor worn for a whole day
- The two pooled analyses disagree. In the 30-trial analysis the day-long measurement could not be told apart from chance against a dummy drink: p = 0.101 for the top number and p = 0.166 for the bottom one. An earlier pooled analysis of 24 studies did reach significance on the top number, at 1.30 mmHg lower than control (2.49 to 0.11 lower), while its bottom number was 0.57 mmHg on an interval running from 1.49 lower to 0.35 higher, which includes no difference. Either way the day-long reading, which is harder to influence by expectation, moves less than the clinic reading.
- The subset of the pooled trials that used 24-hour monitoring, in adults with normal to mildly raised blood pressure
- Studies in people disagree
- Source [04]Source [19]
- Blood pressure, as the Cochrane reviewers pooled it
- The top number was 2.45 mmHg lower than control (95% confidence interval 4.30 to 0.60 lower). The bottom number was 0.67 mmHg lower, on an interval running from 1.48 lower to 0.14 higher, which includes no difference. The reviewers concluded that the review does not support an effect of fermented milk on blood pressure, giving as their reasons that the effect was very modest, appeared in only one of the two numbers, and came from trials that were very heterogeneous and several of which had weak methods.
- 15 randomised trials in 1,232 adults, 650 men and 582 women
- Studies in people disagree
- Source [05]
- Blood pressure in the one American trial, where the two ways of measuring disagreed
- Measured by a monitor worn through the day, the top number fell 3.6 mmHg on the peptide against no change on the dummy (P = .013). Measured in the clinic on the same people, it fell 7.8 mmHg on the peptide against 8.6 mmHg on the dummy — that is, the dummy did slightly better. This is the clearest single illustration of why a clinic reading alone cannot settle this question.
- 91 adults with stage 1 or stage 2 high blood pressure randomised, 81 analysed, 75 mg of a lactotripeptide product twice a day for 6 weeks against a dummy
- One small study
- Source [21]
- Blood pressure measured at home in Japanese adults
- The top number changed by 0.7 mmHg down on the peptide against 2.2 mmHg up on the dummy, which was not statistically significant (P = 0.10). The bottom number changed by 0.9 down against 1.2 up, which was (P = 0.04). Note what the comparison is doing: most of the gap comes from blood pressure rising during the dummy period, not falling during the peptide period.
- 26 Japanese adults with blood pressure just above normal, 2.0 mg IPP and 1.4 mg VPP a day for 8 weeks in a crossover against a dummy
- One small study
- Source [14]
- How much of the peptide reaches the blood
- Peak IPP in the blood was 897 picomoles per litre after the lactotripeptide drink against 555 after the dummy drink, and total exposure over the following hours was 2.1 times higher (P < 0.001). Both figures are far below the 5 micromoles per litre that half-blocks the target enzyme in a dish — roughly five thousand times below it.
- 6 healthy men and women, single doses, crossover against a dummy drink
- One small study
- Source [08]Source [10]
What can go wrong
3 effects
Nothing in the trials has separated these peptides from a dummy drink. In the one trial that published the split by group, 21.7 per cent of people on the peptide reported a side effect against 32.3 per cent on the dummy, no serious events occurred, and three people stopped because of a side effect — two of them on the dummy. Across 15 pooled trials in 1,232 people, 40 left early in total. The US regulator's public food and supplement complaints database holds no reports at all under any of the product names, which is an absence of data rather than a safety record. The real cautions are about what has not been studied: this is a milk product and unsuitable for anyone allergic to cow's milk protein; no trial has enrolled anyone pregnant, breastfeeding or under eighteen; and no study has been designed to test what happens alongside blood pressure medication, which several trials specifically excluded and two of the pooled trials enrolled.
- Any side effect at all, counted against a dummy drink
- No serious side effects were reported in that trial. Most of what was recorded was infections and colds, then headaches and similar, then stomach and gut complaints. Two events were rated severe: one headache and one shingles. Three people stopped because of a side effect — two of them on the dummy, with palpitations and with pain in the lower abdomen, hip and lower back, and one on the peptide, with a bloated abdomen and breathlessness.
- Fewer on the peptide than on the dummy. In the one trial that published the split, 21.7% of people taking the peptide reported a side effect against 32.3% taking the dummy. Counting only events that began during treatment, it was 16.7% against 16.0% — no difference.
- Source [21]
- People dropping out of the trials
- The reviewers describe attrition as generally low and record no serious adverse events among the included trials. That is a statement about tolerability over a few weeks in people who were mostly healthy apart from their blood pressure. It says nothing about months or years, because no trial ran that long.
- Low. Across the 15 randomised trials the Cochrane reviewers pooled, 40 people in total left the studies early, out of 1,232.
- Source [05]
- Complaints sent to the US food and supplement regulator
- An empty database is not a safety record. It means these products are sold in small enough numbers in the United States, or under enough different names, that nothing has been filed under any of them — not that nothing has happened to anyone. The same database holds hundreds of reports for better-known supplements, which is the comparison to keep in mind before reading anything into a zero.
- None. Searching the US regulator's public complaints database for products named lactotripeptide, AmealPeptide, Ameal or Evolus returns no reports at all, on 4 August 2026.
- Source [22]Source [23]
Who it is known to be dangerous for
One group is obvious and one is a gap rather than a warning. The obvious one: these products are milk. The peptides are cut out of casein, the main protein in cow's milk, and the drinks that carry them are fermented milk — an analysis of the Finnish product Evolus measured 6.9 mg of VPP and 6.1 mg of IPP per litre of the drink itself. Anyone allergic to cow's milk protein should treat these as a milk product, because that is what they are, and no trial has enrolled anyone with a milk allergy. The gap: nothing else has been established, in either direction. These peptides are meant to act on the same enzyme that a very common class of blood pressure tablets blocks, and no study has been designed to test what happens when someone takes both. Several of the trials specifically excluded people already on blood pressure medication, while two of the pooled trials enrolled them — 26 of the 30 people in one and 16 of the 39 in another. No published trial has enrolled anyone who is pregnant or breastfeeding, or anyone under eighteen. Because this is regulated as a food rather than a medicine, there is no warnings section anywhere for a doctor or a reader to consult.
The amounts the studies used
7 amounts
These are the amounts the studies below gave their participants, and they are here as facts about those studies. They are not a recommendation, not a starting point and not a range to pick from. What a person should take, if anything, is a question for a doctor who knows them.
- The 18 randomised trials in Japanese participants that have been pooled together. Each used one fixed amount; the amounts differed between trials
- Between 1.8 mg and 17.1 mg of the two peptides a day, in fermented milk drinks or tablets, against a dummy
- 2 to 12 weeks, depending on the trial
- Source [24]
- Engberink et al. 2008, the trial that compared three manufacturing routes in Dutch adults with raised blood pressure
- 14 mg of lactotripeptides a day in 200 ml of a dairy drink — made by concentrating fermented milk, by enzyme digestion, or synthesised chemically — against a dummy drink
- 8 weeks, after a 2-week run-in on the dummy and followed by a 2-week wash-out
- Source [06]
- van der Zander et al. 2008, the largest single European trial, in mildly hypertensive Dutch adults
- 10.2 mg a day of enzyme-made lactotripeptides in a yogurt beverage, against a dummy
- 8 weeks
- Source [07]
- van Mierlo et al. 2009, two crossover trials measuring blood pressure across a whole day
- 200 g a day of a dairy drink with 5.8 mg IPP and 4.4 mg VPP in the first study; 100 g a day with 2.7 mg IPP, 1.9 mg VPP and 350 mg of added potassium in the second
- Two 4-week periods separated by a 4-week gap, in each study
- Source [20]
- Germino et al. 2010, the American trial in stage 1 and stage 2 high blood pressure
- 75 mg of a commercial lactotripeptide powder twice a day, against a dummy
- 6 weeks
- Source [21]
- Tomiyama et al. 2019, home blood pressure and vessel and kidney measurements in Japanese adults
- 2.0 mg IPP and 1.4 mg VPP a day, against a dummy
- 8 weeks on each, with a 4-week gap between
- Source [14]
- Foltz et al. 2007, the study of how much reaches the blood
- A single serving of a lactotripeptide-enriched yogurt beverage, taken fasted or after a meal, against a dummy beverage
- Single doses, with blood sampled over the following hours
- Source [10]
What nobody has measured
15 unknowns
- Whether any of this changes what happens to a person: no trial has run long enough or been large enough to count a heart attack, a stroke or a death.
- Why trials run in Japan report roughly four times the effect of trials run in Europe — population, diet, salt, trial methods and publication practice have all been proposed and none has been tested.
- Whether there is any effect at all on blood pressure measured across a whole day, which is the measurement that pooling finds non-significant while pooling the clinic reading finds a small difference.
- How the peptides could work, given that the amount reaching the blood is around five thousand times below the concentration needed to half-block their supposed target in a dish.
- Why cutting the vagus nerve abolished the effect in rats while a conventional ACE-blocking drug kept working — nobody has followed that finding into a person.
- Whether the effect lasts: the longest published randomised trial ran 21 weeks, and the pooled analyses found no relationship between how long treatment lasted and how large the difference was.
- Whether the dose matters, and in which direction: the pooled trials span roughly 1.8 mg to 17.1 mg a day, and the largest pooled analysis found the trials giving 10 mg a day or less reported a bigger difference than the trials giving more (3.81 mmHg against 1.32 mmHg on the top number, p = 0.027), which is the opposite of a dose-response and has no explanation.
- Whether it does anything in people with properly high blood pressure rather than blood pressure slightly above normal, where most of the trials were done.
- What happens if someone takes these alongside a blood pressure medicine — several trials excluded people on treatment, and no interaction study exists.
- Whether it is safe or does anything in pregnancy, in breastfeeding or in children: no published trial has enrolled any of them.
- Whether the arterial stiffness and kidney readings mean anything, both of which rest on a single 26-person crossover funded by the manufacturer.
- The result of a 54-person American trial of these peptides in coronary artery disease that finished in May 2012 and has posted nothing.
- Whether the result would look the same if an independent group ran the trial: the Cochrane reviewers found that every included trial but one was funded by a company with a financial interest in the product, and in several of them authors were employees of that company.
- How much of the published picture is missing: the largest pooled analysis identified both publication bias and a small-study effect, and correcting for them moved the result towards no difference in one of the two blood pressure numbers.
- What users actually report, because there is nowhere to read it — no forum, subreddit, patient organisation or published survey about these products could be opened and checked, and the US food and supplement complaints database holds no reports under any of the product names.
Questions people ask
8 questions
- Do lactotripeptides actually lower blood pressure?
- Barely, if at all, and it depends entirely on which trials you count and how the blood pressure was measured. Pooling around thirty randomised trials gives about 3 mmHg off the top number compared with a dummy drink — but when blood pressure is measured by a monitor worn for a whole day instead of by a single clinic reading, the difference disappears into chance. The Cochrane reviewers who pooled fifteen of these trials concluded the evidence does not support an effect, because what was found was very modest, showed up in only one of the two numbers, and came from trials that were very heterogeneous and several of which had weak methods.
- Source [04]Source [05]
- Why can't a European product say these peptides are good for blood pressure?
- Because the claim was formally assessed and refused. The European Food Safety Authority looked at it twice — once at the European Commission's request and once on an application from the Finnish dairy company Valio — and concluded both times, in the same words, that a cause and effect relationship has not been established between the consumption of IPP and VPP and maintenance of normal blood pressure. In 2013 the European Commission turned that into law, refusing to authorise the wording "Peptides IPP and VPP help to maintain normal blood pressure" in Commission Regulation (EU) No 1017/2013. The products themselves stay legal as food; the claim on the packet does not.
- Source [01]Source [02]Source [03]
- Why do Japanese studies show a much bigger effect than European ones?
- Nobody knows, and that is the honest answer. Pooled together, trials run in Japan report the top blood pressure number falling 5.54 mmHg more than on a dummy drink, while trials run in Europe report 1.36 mmHg — and the difference between those two groups of trials is itself statistically significant. Explanations that have been offered include a genuine difference between populations, differences in diet and salt intake, and simply weaker trial methods in the studies reporting the larger effects. The Cochrane reviewers leaned towards the last one. None of the three has been tested by running the same trial in both places.
- Source [04]Source [05]Source [24]
- Lactotripeptides vs ACE inhibitors — can these replace blood pressure tablets?
- No, and the size of the numbers is the reason. Lactotripeptides block the same enzyme as a common class of blood pressure tablets, but only in a test tube: the amount that reaches a person's blood after drinking them is roughly five thousand times below the concentration that half-blocks that enzyme in a dish. When the mechanism was tested directly in 135 people over 8 weeks, enzyme activity in the blood did not change relative to a dummy drink. No trial has compared these peptides against a blood pressure medicine, and no trial has been designed to test taking both together. This register does not tell anyone what to take or what to stop taking.
- Source [06]Source [08]Source [10]
- What are the side effects of lactotripeptides?
- Nothing has separated them from a dummy drink. In the one trial that published the breakdown, 21.7% of people on the peptide reported a side effect against 32.3% on the dummy, and no serious side effects were reported at all. Across fifteen pooled trials in 1,232 people, 40 people in total left early. The real caution is not a side effect but a fact about the product: it is made from milk protein, so it is not for anyone allergic to cow's milk, and nobody has tested it in pregnancy, in children, or alongside blood pressure medication.
- Source [05]Source [21]
- Can you buy lactotripeptides, and what are they sold as?
- Yes — as ordinary food and food supplements, not as medicine. They are sold as fermented milk drinks and as capsules and tablets of a milk protein hydrolysate, under names including the Japanese Calpis products built on AmealPeptide and the Finnish Valio drink Evolus, whose measured content is 6.9 mg of VPP and 6.1 mg of IPP per litre. In Europe none of them may carry a blood pressure claim on the label. This register does not link to shops and does not say what anyone should take.
- Source [01]Source [25]Source [26]
- Are lactotripeptides banned in sport?
- No. Neither peptide, nor lactotripeptides under any name, nor casein or milk peptides appear anywhere in the World Anti-Doping Agency's 2026 Prohibited List. The catch-all first section of that list covers pharmacological substances with no regulatory approval for human use; a peptide that occurs in ordinary fermented milk and is sold as food does not fall under it.
- Source [09]
- Are these peptides natural, and are they already in food?
- Yes. Both sequences sit inside cow's milk's main protein, beta-casein — IPP at positions 74 to 76 of the mature protein and VPP at 84 to 86 — and they are released whenever that protein is broken down, which is why they turn up in fermented milk and in sourdough made from wheat, rye and malt. The manufactured versions are the same molecules, made in larger amounts by fermenting milk with a particular bacterium or by cutting casein with enzymes. In the absorption study, even the dummy drink produced a measurable amount of IPP in the blood.
- Source [10]Source [11]Source [27]
Sources
27 sources
- [01]Commission Regulation (EU) No 1017/2013 of 23 October 2013 refusing to authorise certain health claims made on foods — recitals 7 and 8 and the Annex: applicant Valio Ltd, claim "Peptides IPP and VPP help to maintain normal blood pressure", refused (EUR-Lex, CELEX 32013R1017) (2013)
- [02]EFSA – Scientific Opinion on the substantiation of a health claim related to isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) and maintenance of normal blood pressure pursuant to Article 13(5), EFSA Journal 2011;9(9):2380 (2011)
- [03]EFSA – Scientific Opinion on the substantiation of health claims related to IPP and VPP and maintenance of normal blood pressure (ID 661, 1831, 1832, 2891, further assessment) pursuant to Article 13(1), EFSA Journal 2012;10(6):2715 (2012)
- [04]Fekete et al., casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials — 30 trials, 33 datasets, with the Japanese versus European subgroup split and the publication-bias finding (Nutrients) (2015)
- [05]Usinger, Reimer and Ibsen, Fermented milk for hypertension — Cochrane Database of Systematic Reviews, 15 trials in 1,232 participants, concluding the review does not support an effect (2012)
- [06]Engberink et al., lactotripeptides show no effect on human blood pressure: double-blind randomised controlled trial in 135 Dutch adults, with plasma ACE activity and angiotensin II unchanged (Hypertension) (2008)
- [07]van der Zander et al., enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects — 275 participants, p = 0.66 and 0.72 against placebo (American Journal of Clinical Nutrition) (2008)
- [08]Nakamura et al., purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk — half-blocking concentrations of 5 µM for Ile-Pro-Pro and 9 µM for Val-Pro-Pro (Journal of Dairy Science) (1995)
- [09]WADA International Standard Prohibited List 2026, valid 1 January 2026 — full text searched 4 August 2026: no entry for these peptides, casein or milk peptides in any section (2026)
- [10]Foltz M et al. Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation, J Nutr 2007;137:953-8 — plasma 897 against 555 pmol/L (2007)
- [11]Li M et al. Bioavailability of the antihypertensive lactotripeptides IPP and VPP, Compr Rev Food Sci Food Saf 2019;18:1097-1110 — absorbed fraction about 0.1% (2019)
- [12]Gregory KS et al. Structural basis of lactotripeptide binding to angiotensin-converting enzyme, FEBS Lett 2024;598:242-251 — X-ray crystallography showing a preference for the N-domain (2024)
- [13]openFDA CAERS — searches for lactotripeptide, AmealPeptide, Ameal and Evolus all return NOT_FOUND: the US food-complaint database holds no report naming these products
- [14]Tomiyama et al., effects of lactotripeptide supplementation on tele-monitored home blood pressure and on vascular and renal function in prehypertension (Circulation Reports; funded by Asahi Calpis Wellness) (2019)
- [15]NCT00924157, effect of Ile-Pro-Pro on endothelial function in patients with coronary artery disease, 54 participants, completed May 2012, no results posted (2012)
- [16]Nakamura et al., antihypertensive effect of sour milk and peptides isolated from it in spontaneously hypertensive rats (Journal of Dairy Science) (1995)
- [17]Effects of the bioactive peptides Ile-Pro-Pro and Val-Pro-Pro upon autonomic neurotransmission and blood pressure in spontaneously hypertensive rats (Autonomic Neuroscience) (2017)
- [18]Cicero et al., blood pressure lowering effect of lactotripeptides assumed as functional foods: meta-analysis of 18 trials with Asian and Caucasian subgroups (Journal of Human Hypertension) (2011)
- [19]Lactotripeptides intake and blood pressure management: meta-analysis of 24 studies with 28 trials in 1,919 people (Nutrition, Metabolism and Cardiovascular Diseases) (2013)
- [20]van Mierlo et al., lactotripeptides do not lower ambulatory blood pressure in untreated whites: results from 2 controlled multicenter crossover studies (American Journal of Clinical Nutrition) (2009)
- [21]Germino et al., the impact of lactotripeptides on blood pressure response in stage 1 and stage 2 hypertensives (Journal of Clinical Hypertension; authors are advisors to or grant-holders from Calpis USA) (2010)
- [22]openFDA food, dietary supplement and cosmetic adverse event reports (CAERS), brand-name search for lactotripeptide, retrieved 4 August 2026 — no matches found
- [23]openFDA CAERS, brand-name search for AmealPeptide, retrieved 4 August 2026 — no matches found
- [24]Chanson-Rolle et al., influence of the lactotripeptides IPP and VPP on systolic blood pressure in Japanese subjects: meta-analysis of 18 randomised trials in 1,194 people (PLOS ONE; sponsored by Calpis Co.) (2015)
- [25]Quantification of dabsylated di- and tri-peptides in fermented milk — measured 6.9 mg/L VPP and 6.1 mg/L IPP in Evolus (Valio Ltd, Finland) (Food Chemistry) (2012)
- [26]Milk protein peptides with angiotensin I-converting enzyme inhibitory activity — review naming Evolus and Calpis as the marketed products (Critical Reviews in Food Science and Nutrition) (2010)
- [27]UniProt P02666, bovine beta-casein — sequence containing IPP and VPP, retrieved 4 August 2026