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Bon3.5
Bonito Peptides Research
Mostly mechanism / observationalHigh safety
12 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Bonito Peptides studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality randomised trials published 1992–2020 with a typical study size of 29 participants.
Based on 12 studies · 5 RCTs · 128 total participants
Confidence
Moderate
By outcome
Heart & blood pressureModest systolic/diastolic BP reduction (roughly 5-9 mmHg systolic in small Japanese trials; much smaller in broth studies), concentrated in mild/high-normal hypertension — not in normotensive people; trials are small, short, and often industry-affiliated. Not a replacement for antihypertensive medication. · 1-4 weeks (BP), sustained with continued intake
Mostly mechanism / observational11 studies
Safety profile
Too few graded studies1 study
Older research base
Newest study from 2020
199220062020
1RCTn=29 · very small study2000
In the VY-group, reduction in systolic (S) and diastolic (D) BP was 9.7 and 5.3 mm Hg (P < 0. 001) at 1 week, and 9.3 and 5.2 mm Hg (P < 0.001) at 4 weeks, following the start of the E period, respectively.
Kawasaki T, Seki E, Osajima K, Yoshida M, Asada K, Matsui T, Osajima Y. · J Hum Hypertens (2000)
Randomized double-blind placebo-controlled trial in 29 mild-hypertensive volunteers
A 100-mL drink containing 3 mg of Val-Tyr (VY) was given twice daily for 4 weeks
SBP/DBP fell ~9.3/5.2 mmHg in the VY group with no change in placebo; BP rose again during recovery
40 subjects with mild hypertension or high-normal blood pressure (130 mmHg < or = systolic blood pressure (SBP) < 160 mmHg and/or 80 mmHg < or = diastolic blood pressure (DBP) < 100 mmHg) showed a significant decrease in SBP, from 142.0 +/- 10.3 mmHg at the start of the test to 134.4 +/- 11.1 mmHg during the first week of the test period, after which similar values were seen throughout the test period (13 weeks).
Kawasaki T, Jun CJ, Fukushima Y, Kegai K, Seki E, Osajima K, Itoh K, Matsui T, Matsumoto K. · Fukuoka Igaku Zasshi (2002)
Randomized double-blind placebo-controlled trial in 63 subjects (mild HTN, high-normal, and normal BP)
A vegetable drink with 0.5 g sardine peptides providing 0.4 mg Val-Tyr/day for 13 weeks
SBP fell ~7-8 mmHg and DBP significantly in the (pre)hypertensive subset versus control
3RCT2009
In group-H, both FDWG and FDW significantly decreased systolic (SBP, -7.6 +/- 4.0 and -5.5 +/- 1.5 mmHg, p<0.05, respectively) and diastolic (DBP, -10.6 +/- 4.0 and -7.6 +/- 1.7 mmHg, p<0.01, respectively) BP compared to the baseline (0-week) value at 12 weeks, respectively.
Tanaka H, Watanabe K, Ma M, Hirayama M, Kobayashi T, Oyama H, Sakaguchi Y, Kanda M, Kodama M, Aizawa Y. · J Clin Biochem Nutr (2009)
Double-blind, placebo-controlled, randomized study of a fermented drink containing vinegar and dried bonito (with or without GABA)
In hypertensive volunteers, SBP fell ~5.5-7.6 mmHg and DBP ~7.6-10.6 mmHg over 12 weeks
Both the GABA and non-GABA (dried-bonito) drinks lowered BP — the bonito component is implicated
LKPNM (IC50 = 2.4 microM) was found to be hydrolyzed by ACE to produce LKP (IC50 = 0.32 microM) with 8-fold higher ACE-inhibitory activity relative to the parent peptide or LKPNM, suggesting that LKPNM can be regarded as a prodrug-type ACE-inhibitory peptide.
Fujita H, Yoshikawa M. · Immunopharmacology (1999)
Isolated LKPNM and seven other ACE-inhibitory peptides from the thermolysin digest of dried bonito (Katsuobushi)
LKPNM (IC50 2.4 µM) is cleaved by ACE to the ~8-fold more potent LKP (IC50 0.32 µM) — a prodrug mechanism giving prolonged effect
In SHR rats, LKPNM's antihypertensive activity was ~66% that of captopril on a molar basis (LKP ~91%)
In a long-term feeding experiment, in which 3 week old SHR were fed a standard chow supplemented with the digest for 7 weeks, elevation of the systolic blood pressure was significantly suppressed by 15 mg/kg per day of the digest.
LKPNM, which was isolated from the thermolysin digest of dried bonito was activated 8-fold by ACE itself and showed a prolonged effect after oral administration.
Yoshikawa M, Fujita H, Matoba N, Takenaka Y, Yamamoto T, Yamauchi R, Tsuruki H, Takahata K. · Biofactors (2000)
Review of food-protein-derived ACE-inhibitory and other bioactive peptides
Highlights bonito LKPNM as a prodrug-type ACE inhibitor with a prolonged oral effect
Places bonito peptides in the broader food-peptide / lifestyle-disease context (alongside ovokinin, milk peptides)
Proteolytic digestion of dried bonito muscle with thermolysin produces a hydrolysate with strong angiotensin-converting enzyme (ACE) inhibitory activity and is the basis of a dietary supplement with antihypertensive activity.
Treatment with some ACE inhibitory small peptides (VY, Ile-Trp [IW], and Ile-Val-Tyr [IVY]) had diverse effects on serum-stimulated VSMC proliferation that were independent of their ACE inhibitory activity, though only VY exerted a potent antiproliferative action.
Matsui T, Ueno T, Tanaka M, Oka H, Miyamoto T, Osajima K, Matsumoto K. · Hypertens Res (2005)
Cell-culture study of Val-Tyr on human vascular smooth-muscle-cell proliferation
VY inhibited serum- and angiotensin-II-stimulated proliferation, partly via L-type Ca2+ channel inhibition and independent of ACE inhibition
Suggests a vascular mechanism beyond simple ACE inhibition