Bioactive peptides from food: what the milk peptide studies show

What bioactive peptides are

A 2018 review in the journal Nutrients defines bioactive peptides as protein pieces with a helpful effect on body functions. That effect goes beyond the food's known nutrition. The review says these pieces sit hidden inside larger food proteins.

The pieces are released in three ways, according to the same review. Enzymes can cut them out, food processing can free them, or microbes can release them during fermentation. The sour milk described below was made by fermentation.

The review lists many protein sources. Animal sources include eggs, milk proteins such as casein and whey, and meat. Plant sources include soy, oats, beans, peas, lentils, wheat, canola, flaxseed and hemp seed. Marine sources include fish, squid and oysters.

Researchers can test a peptide at four levels: chemical tests in a lab, cells in dishes, animals and people. The review names four reasons that commercial use has been delayed. These are production problems, limited data on digestion and absorption, unclear mechanisms and a lack of well-designed trials.

What happens to food peptides in the gut

The 2018 review says scientists once thought the gut broke all proteins down to single amino acids. It now describes many peptides that cross the gut lining under normal conditions. One transport protein, called PepT1, carries short peptides across that lining.

A 2004 review in the British Journal of Nutrition studied this question for peptides that block an enzyme called ACE. ACE helps the body control blood pressure. The review says blocking ACE in a lab test does not always lower blood pressure in a living body.

To work after a meal, the review says, a peptide must survive digestive enzymes and pass through the gut wall into the blood. Peptides that contain the amino acid proline tend to resist digestion. Shorter peptides tend to keep more activity after absorption.

How strong is the evidence? Absorption has been measured for some peptides only. That finding applies to the peptides tested and does not cover every peptide in a food.

How the milk peptides VPP and IPP were found in 1995

Two 1995 papers in the Journal of Dairy Science list the lead author at Calpis, a Japanese food company. The researchers fermented milk with a starter culture, a mix of live microbes. It contained Lactobacillus helveticus, a bacterium, and a yeast. The ACE-blocking activity of the milk rose during fermentation.

The team purified two peptides from the sour milk. Each has three amino acids. Val-Pro-Pro (VPP) is valine, proline, proline. Ile-Pro-Pro (IPP) is isoleucine, proline, proline. The paper says these two peptides gave most of the milk's ACE-blocking activity in the lab test.

A second paper fed the sour milk or the two peptides to rats bred to have high blood pressure. One dose lowered systolic blood pressure, the top number of a reading, 6 to 8 hours later. The pressure returned to its starting level by 24 hours.

Larger amounts did not change blood pressure in rats with normal blood pressure. That result applies to single doses in rats.

What trials in people found about blood pressure

A Dutch randomized trial, published in 2008, enrolled 135 adults with raised systolic blood pressure. None were taking blood pressure medicine. For 8 weeks, they drank a dairy drink with VPP and IPP made by one of three methods, or a drink without them (placebo).

The peptide drinks did not significantly change systolic or diastolic blood pressure compared with placebo. Diastolic pressure is the bottom number of a reading. Home and 24-hour readings also showed no significant effect. That result applies to Dutch adults over 8 weeks.

A 2015 analysis in Nutrients pooled 30 randomized trials in adults, each lasting at least 4 weeks, with 2,200 participants. On average, systolic pressure fell 2.95 mmHg and diastolic pressure fell 1.51 mmHg. The unit mmHg, millimeters of mercury, is the unit on a blood pressure reading.

Fourteen of the trials took place in Japan, and drops were larger there than in European trials. Two trials included people taking blood pressure medicine. The 24-hour readings showed no significant change. The authors declared no conflicts of interest, and a UK research council funded the first author.

The 2015 authors also found signs of publication bias, where studies with positive results get published more often. A method that estimates missing studies cut the systolic drop to 1.64 mmHg. The diastolic change was then no longer significant.

A 2013 analysis in the American Journal of Hypertension pooled 14 trials of 1,306 Europeans. It found a 1.28 mmHg average drop in systolic pressure. Two of its four authors were paid by Calpis for the analysis and writing.

These studies measured blood pressure readings in adults over weeks to months. The sources reviewed here do not report heart attacks, strokes or a full safety review. The Dutch trial abstract does not report its funding.

What Europe's food safety agency concluded

The European Food Safety Authority (EFSA) reviews health claims for foods sold in the European Union. Its nutrition panel looked at VPP and IPP and normal blood pressure twice. The first opinion, in 2011, answered an application from Valio Ltd, sent through Finland's food authority.

In 2011, the panel noted that 13 trials found no effect on blood pressure. Four of those trials were large enough to detect small differences. Seven of the eight studies that reported an effect had major method problems.

In 2012, at the European Commission's request, the panel assessed the same claimed effect for the general population. It noted that 15 human studies found no effect, and seven of them were large enough to detect small differences. Nine of the ten studies that reported an effect had method weaknesses.

Both opinions said the animal studies added no information about people. Both said no convincing evidence was provided for how the peptides could have this effect at the proposed amount. Both concluded that a cause-and-effect link between eating VPP and IPP and normal blood pressure was not established.

How strong is the evidence? Studies in people tested blood pressure, and the results conflict. Pooled averages show small drops, larger in Japanese trials. EFSA twice found the link not established.

How food peptide products are classified in the United States

FDA's dietary supplement questions page, current as of August 2026, says FDA does not approve supplements before they are sold. A company must have support for a claim about how a product affects the body. FDA generally does not approve those claims before use.

The same page says a supplement sold to treat, prevent or cure a disease meets the definition of a drug. FDA advises people to talk with a doctor, pharmacist or other health professional before using a supplement. It notes that some supplements might interact with medicines.

The 2018 review says the United States and Canada give no legal status to the term functional food. The review uses that term for a food with a specific health benefit. Japan has a regulated category called food for specific health uses, or FOSHU. The review calls FOSHU the closest legal match to a functional food.

How a seller's claim compares with the records

Consider a hypothetical listing for a milk peptide supplement that says it lowers blood pressure. The records reviewed here set limits on that claim. The 1995 blood pressure results came from rats. Trials in people found small and mixed results.

EFSA assessed a related claim, maintaining normal blood pressure, and found a cause-and-effect link not established. FDA does not approve supplements before they are sold. Trial results apply to the products those trials tested.

Check four things in a claim about a food peptide:

• The exact peptide: a named sequence, such as VPP, or an unnamed mix of protein pieces.
• The test level: a lab test, cells, animals or people.
• For studies in people: who took part, for how long, what was measured and who paid.
• Regulator review: whether an agency such as EFSA assessed the exact claim, and what it concluded.