Benefits
Small average change in blood pressure across pooled trials
Meta-analyses of randomized trials in adults find small average reductions: about 3 mmHg systolic across 30 trials and under 2 mmHg across 28 trials. Signs of publication bias shrank the estimate, so the true effect may be smaller. This is not a treatment for high blood pressure.
Blood pressure results differ between Japanese and European trials
In 18 Japanese trials, systolic pressure fell about 5.6 mmHg more than placebo; in 14 European trials the extra drop was about 1.3 mmHg. Both reviews had authors paid by the main producer. Four trials in white adults, including Dutch trials of 275 and 135 people, found no effect. Why results differ by region is not known, and EU food safety experts found a benefit not established.
24-hour and home blood pressure readings
Office readings can be swayed by stress at the clinic, so 24-hour monitoring is a stricter test. Pooled 24-hour results were small or not significant. Dutch trials and a Finnish trial at 50 mg/day found no 24-hour difference from placebo, while an Italian crossover trial in 40 adults reported some lower 24-hour readings. A small Japanese trial found home readings about 2 to 3 mmHg lower.
Arterial stiffness markers in small trials
In a 24-week Finnish trial of 89 adults with raised blood pressure, peptide-rich fermented milk lowered the augmentation index, a stiffness measure, versus placebo, while blood pressure did not differ. Two small Italian trials reported lower pulse wave velocity, one against placebo and one only against starting values, and a Japanese trial found no change. These are markers in small, short trials, not heart outcomes.
Blood pressure with peptide-rich fermented milk drinks
The first studies used fermented milks rather than tablets. In a 21-week trial of 39 adults with hypertension, a daily 150 mL fermented milk gave home systolic pressure about 7 mmHg lower than a control drink. An 8-week Japanese sour-milk study in 30 older patients, most on medication, found a within-group drop that only trended past placebo.
Mechanism of action
ACE inhibition (test-tube work)
In the test tube, VPP and IPP weakly block angiotensin-converting enzyme (ACE), which makes the vessel-narrowing hormone angiotensin II. In a human study the peptides were poorly absorbed, IPP rose only briefly in the blood, VPP stayed below the measurable level and ACE activity did not change, so this mechanism is not shown in people.
Possible effects on artery walls (unconfirmed)
Some trials report changes in arterial stiffness measures, and researchers have proposed effects on the artery lining. An Italian crossover trial reported a better blood flow response after the peptides, but in a Finnish 24-week trial an endothelial function test did not change and a Japanese trial found no difference in vessel function tests, so how the peptides might affect blood vessels in people is unknown.
Clinical trials
Systematic review and meta-analysis of randomized controlled trials of casein lactotripeptides on systolic and diastolic blood pressure in adults, by a university group with no producer authors (Fekete et al. 2015, Nutrients)
Adults in 30 randomized trials (33 data sets), mostly from Japan and Europe, searched to May 2014.
Pooled changes were -2.95 mmHg systolic and -1.51 mmHg diastolic versus control. Japanese studies showed significantly larger drops than European ones. 24-hour ambulatory blood pressure did not change significantly, and publication bias and small-study effects were found; allowing for them weakened the systolic result and made the diastolic result non-significant.
Randomized placebo-controlled trial of Lactobacillus helveticus LBK-16H fermented milk from the Valio research centre, with blood pressure measured at home each week (Seppo et al. 2003, Am J Clin Nutr)
39 adults with hypertension (baseline about 155/97 mmHg), 150 mL/day of fermented milk or a control drink for 21 weeks after a 2-week run-in.
Home systolic blood pressure was 6.7 mmHg lower in the fermented milk group than in the control group (P = 0.030). The 3.6 mmHg difference in diastolic pressure was not statistically significant (P = 0.059). A small trial run by the product's maker.
Two multicenter, randomized, placebo-controlled crossover trials by Unilever of dairy drinks with enzymatically produced lactotripeptides, measured by 24-hour ambulatory monitoring (van Mierlo et al. 2009, Am J Clin Nutr)
White adults with untreated raised blood pressure: 69 people given 5.8 mg IPP plus 4.4 mg VPP a day, and 93 people given 2.7 mg IPP plus 1.9 mg VPP with 350 mg potassium a day, each for 4 weeks.
24-hour systolic and diastolic blood pressure did not differ between the peptide drinks and placebo in either trial (P > 0.10). Office systolic pressure fell by more than 5 mmHg during both studies, and the difference from placebo was not significant (P > 0.10). The authors concluded the data do not support a blood pressure effect in white Europeans.
Double-blind, placebo-controlled parallel trial of peptide-rich Lactobacillus helveticus fermented milk, measuring the augmentation index by pulse wave analysis; three authors were Valio employees and Valio supplied the products (Jauhiainen et al. 2010, Eur J Clin Nutr)
89 adults with hypertension; 5 mg/day of the tripeptides for 12 weeks, then 50 mg/day for 12 weeks, or a placebo milk drink.
At the end, the augmentation index fell 1.53% with the peptides and rose 1.20% with placebo (P = 0.013). An endothelial function index did not change, and office and 24-hour blood pressure did not differ from placebo.
Randomized, double-blind, placebo-controlled crossover trial of casein lactotripeptides with 4-week periods and a 4-week washout (Cicero et al. 2016, Metab Syndr Relat Disord)
40 non-smoking adults with metabolic syndrome and suboptimal blood pressure control, 10.2 mg/day of lactotripeptides or placebo.
During the peptide period, office systolic pressure fell 3.4 mmHg and diastolic 3.1 mmHg, and these changes were significantly larger than with placebo (P < 0.01). Pulse wave velocity fell 0.8 m/s versus 0.1 m/s with placebo, and some 24-hour measures improved compared with placebo. Short periods and a small group.
Randomized, double-blind, placebo-controlled crossover trial with 8-week periods and 7-day tele-monitored home blood pressure as the main outcome, funded by Asahi Calpis Wellness (Tomiyama et al. 2019, Circ Rep)
26 Japanese adults aged 36 to 57 with prehypertension and no blood pressure medication; tablets with 1.4 mg VPP and 2.0 mg IPP, or caseinate placebo tablets.
At the end of the peptide period, home blood pressure was 127/84 mmHg versus 130/86 mmHg after placebo (P = 0.02 systolic, P = 0.03 diastolic). In the mixed-model analysis of change, diastolic pressure differed between periods (P = 0.04) but systolic only marginally (P = 0.10). Vessel function tests, including pulse wave velocity, did not differ.