Milk Peptides

Milk peptide IPP and VPP and blood pressure

Read the following text and test your understanding on the questions below.

The application

Beneficial effect

The claimed effect is “helps to maintain normal blood pressure”. The target population proposed is mildly hypertensive subjects or subjects with an elevated risk of developing hypertension.

Scientific substantiation

A literature search through PubMed to identify randomized, placebo-controlled, clinical trials (RCTs) and meta-analyses of RCTs published in English which assessed the effects of IPP and VPP at doses 10 mg/day on blood pressure in humans not taking BP-lowering medications.

A total of 20 published intervention studies and one unpublished study, as well as two published and one unpublished meta-analyses of RCTs were identified

Five parallel, placebo-controlled intervention studies compared the effects of sour milk, liquid yoghurt or tablets containing IPP and VPP on blood pressure in hypertensive subjects not on blood pressure-lowering medications. The studies did not appear to be randomized.

A further 15 RCTs were provided. Not all showed an effect of the milk peptides on blood pressure. In studies that showed an effect there were some issues with the study design and the statistical analysis such as having too few subjects, lack of clarity in how often blood pressure was measured, not taking into account confounding factors and not accounting for missing data. A dose response relationship was not established.

Some animal studies and mechanistic (in vitro) studies were also provided for background.

A mechanism of action was proposed (ACE inhibition) although this had been observed with doses that were much higher than that proposed for the health claim.


The EFSA opinion

The following provides short extracts from the EFSA opinion on this health claims application to illustrate EFSA’s conclusions on the aspects below.


The food constituent that is the subject of the health claim is the tripeptides isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP), which can be obtained through fermentation of milk by certain lactic acid bacteria, by enzymatic hydrolysis of casein or by chemical synthesis. All clinical studies presented have been conducted with either directly fermented milk, with powdered fermented milk, or with tripeptides obtained from enzymatically-hydrolysed casein. IPP and VPP can be measured in foods by established methods.

The Panel considers that the food constituent, the tripeptides IPP and VPP, which is the subject of the health claim, is sufficiently characterised.

Beneficial effect

The claimed effect is “helps to maintain normal blood pressure”. The target population proposed by the applicant is mildly hypertensive subjects or subjects with an elevated risk of developing hypertension.

The Panel considers that maintenance of normal blood pressure is a beneficial physiological effect.

Scientific substantiation

In weighing the evidence, the Panel took into account that 13 of the human intervention studies provided, four of which were adequately powered to detect small between-group differences in systolic blood pressure, did not observe an effect of IPP and VPP on systolic blood pressure or diastolic blood pressure; that the interpretation of the results from seven out of the eight studies which reported an effect of IPP and VPP on office systolic blood pressure was hampered by major methodological limitations; that the animal studies did not provide additional information on the effect of IPP and VPP on blood pressure in humans; and that there is no convincing evidence for a mechanism by which IPP and VPP could exert the claimed effect at the proposed dose.

The Panel concludes that a cause and effect relationship has not been established between the consumption of IPP and VPP and maintenance of normal blood pressure.


The claim received a negative opinion from EFSA and was rejected by the EC

Suggested wording


Question 1

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Question 2


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Question 3

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Question 4


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Question 5

What do you understand by ‘characterisation’ in this case? (i.e. What is it in the component of the product that has been identified as having the health effect and has this been sufficiently characterised?)

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Question 6

Do you agree that the effect in question is likely to be beneficial for the general population?

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Question 7

What do you think about the level of evidence provided for the scientific substantiation?

You could consider:

  1. Were randomized controlled trials (RCTs) in humans included
  2. Were the studies performed with the product/compound of interest?
  3. Were the measures of the health effect valid?
  4. Was there a dose-response relationship?
  5. Was there evidence provided for a mechanism by which the product/component has the effect?

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Question 8

Do you think the claim was given a positive opinion?

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