IngredientsThe primary source of bonito peptide is the bonito fish, Katsuwonus pelamis (skipjack tuna). This species belongs to the family Scombridae, the same family as tuna and mackerel. Skipjack tuna (Katsuwonus pelamis) is the most productive and low-value species of tuna, with annual catches of approximately 3.2 × 106 tons. Additionally, the related species Sarda orientalis (oriental bonito) and Auxis thazard (frigate tuna, also called bonito) are used in some preparations. Auxis thazard, also named bonito, is a kind of deep-sea migratory and low-value tuna, and it possesses various biological activities due to its high content of carnosine and anserine.
The term "bonito peptide" is a collective name for a group of bioactive oligopeptides derived from the muscle proteins of these fish. The most chemically defined and widely studied entity is the Katsuobushi oligopeptide (KO), also known commercially as PeptACEâ„¢. The thermolysin digest of dried bonito (katsuobushi), a traditional Japanese seasoning made of bonito muscle, has potent ACE-inhibitory activity when digested by thermolysin, and eight ACE-inhibitory peptides have been isolated from it.
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. A major portion of the ACE activity was shown previously to arise from the peptide Leu-Lys-Pro-Asn-Met (LKPNM).
A FOSHU-approved antihypertensive product, 'Peptide Soup', consists of a katsuobushi (bonito) hydrolysate generated with thermolysin, and the biofunctional peptide therein, LKPNM, has been shown to significantly reduce systolic blood pressure in mildly hypertensive subjects. In addition to beverage products (soup and tea), the bonito peptide is also sold in Japan as a powdered ingredient and in tablet format known as Peptide ACE 3000.
The manufacturing of dried bonito requires multiple boiling steps, fermentation, and washing procedures, yielding condensed bonito extract (BoE). A powdered form of condensed BoE with reinforced dried bonito powders has been manufactured as a dietary supplement.
Commercial food, beverage, and dietary supplement products that provide bonito fish peptides include the bonito fish peptide supplement called Vasotensin®.
A distinct product line based on bonito-derived elastin peptides (marketed as VGPG Elastin®) has been developed for oral skin-health applications. This product contains 100 mg of bonito fish (Katsuwonus pelamis)-derived elastin peptide with a total average molecular weight of 582 Da.
It has been previously documented that the thermolysin digest of "Katsuobushi," or dried bonito, a traditional Japanese food, potently inhibits the angiotensin I-converting enzyme (ACE). However, the traditional use predates modern biochemical understanding of these mechanisms.
Bonito extract (BoE) consists of a mixture of fermented, dried bonito meat, and condensed boiled bonito soup, which has served for centuries as a seasoning or nutritional supplement in the Southern District of Kagoshima prefecture, Kyushu Island, Japan.
Katsuobushi (dried bonito) broth extracted from shaved katsuobushi flakes is an important seasoning that is commonly used in Japanese cuisine. The annual supply of katsuobushi in Japan is estimated to be approximately 35,000 tons, most of which is commercially consumed for the production of katsuodashi (dried bonito broth).
While the isolation and identification of bonito peptides are modern developments rooted in Japanese peptide research, their source—bonito fish—has been used in traditional Japanese and Southeast Asian cuisine for centuries, most famously as katsuobushi (dried, fermented, and smoked bonito flakes) used in dashi broth. In Japanese folk tradition, foods like dashi were considered revitalizing tonics, especially for the elderly, weak, or fatigued.
Katsuobushi undergoes a traditional multi-step artisan preparation: katsuobushi is produced from a fish, bonito, by a variety of processes, including boiling, sun drying, smoking, and mould culturing. These processing steps enzymatically modify the muscle proteins and concentrate the bioactive peptide content of the final product.
Fermented dried bonito and its hot water extracts have been one of the most traditional and popular condiments and, in folk remedies, have served as a nourishing tonic for years in Japan. The modern identification and isolation of specific bioactive peptides from this traditional food represent a translation of centuries-old food culture into contemporary nutraceutical science.
One gram of bonito extract (BoE) contains 638 mg of amino acids, 5.3 mg of DHA, 0.8 mg of EPA, 1.12 mg of niacin, 6.3 mg of anserine (a radical scavenger), and 14.4 mg of taurine (associated with liver function and anti-inflammation).
Anserine is a multifunctional and highly stable histidine carnosine-like dipeptide found in fish skeletal muscles. Bonito contains approximately 1,070 mg of anserine per 100 g of fish flesh.
The bonito hydrolysate is a crude mixture of oligopeptides; a major fraction of oligopeptides fall in the 2–20 kDa range, with a weight-average molecular weight of approximately 5.0 kDa. The key antihypertensive pentapeptide LKPNM is a much smaller molecule. The LKPNM content in KO (Katsuobushi oligopeptide) is 0.17% (w/w).
Hypertension is the most widespread risk factor for many serious cardiovascular diseases. Angiotensin-converting enzyme (ACE) plays a crucial role in cardiovascular physiological regulation by converting angiotensin I to a potent vasoconstrictor, angiotensin II. The inhibition of ACE is the primary mechanism attributed to bonito peptides.
The mode of action of the peptides involves inhibition of ACE, an enzyme of prime importance in blood pressure regulation, making them a potential building block for functional foods and nutraceuticals.
The key ACE-inhibitory peptide, LKPNM, operates as a prodrug: the thermolysin digest of "Katsuo-bushi" (a Japanese traditional food processed from dried bonito) possesses potent inhibitory activity against ACE. From it, eight kinds of ACE-inhibitory peptides were isolated. Of these, LKPNM (IC50 = 2.4 μM) was found to be hydrolyzed by ACE to produce LKP (IC50 = 0.32 μM) with 8-fold higher ACE-inhibitory activity relative to the parent peptide, suggesting that LKPNM can be regarded as a prodrug-type ACE-inhibitory peptide.
Eight ACEI peptides were isolated from the thermolysin digest of dried bonito. Most of them were true inhibitors or precursors that are converted into true inhibitors by ACE or gastrointestinal proteases in vivo. Precursor-type peptides required a longer time than true inhibitors to show maximal antihypertensive effect after oral administration. Thus, the thermolysin digest of dried bonito is a mixture of true inhibitors and precursor peptides differing in maximally effective times.
Some food-derived peptides interfere with the endothelin system, inhibiting ECE, which induces a wide range of physiological effects including vasoconstriction. Pepsin digests of bonito pyloric appendix showed ECE inhibitory activities, and pronase treatment resulted in the disappearance of these inhibitory activities, indicating that peptides were responsible.
Peptides derived from fish protein hydrolysate have also shown antihypertensive effects by blocking Ca2+ channels. Blocking of voltage-dependent calcium channels can reduce Ca2+ influx into vascular muscle cells and thereby suppress vasoconstriction.
Bonito is a marine migratory fish with powerful exercise capability and tight binding proteins. Researchers found that bonito hydrolysates have a high content of carnosine and anserine, which showed antioxidant and uric acid-lowering activities. Only partial polypeptides are responsible for the bioactivities of the hydrolysates.
In studies on peptides associated with hyperuricemia, pelagic fishes such as tuna and bonito have been found to migrate tens of thousands of kilometres at high speeds without causing an acid build-up in the body, a phenomenon attributed to the presence of the important dipeptide anserine.
In a mouse model, bonito extract was associated with reduced granulocyte-colony stimulating factor in sera of female mice, and reduced interleukin (IL)-5, IL-6, and IL-13 at higher doses. These are preliminary animal findings and have not been replicated in controlled human trials.
The use of in vitro ACE-inhibitory activity as the exclusive criterion for potential antihypertensive substances has been questioned, since physiological transformations may occur in vivo, and because other mechanisms of action than ACE inhibition might be responsible for the antihypertensive effect.
A bonito hydrolysate with antihypertensive effect was approved as a Food for Specified Health Use (FOSHU) by the Ministry of Health and Welfare in Japan. The bonito hydrolysate produced using thermolysin contained the active pentapeptide LKPNM, which had significantly reduced systolic blood pressure in mildly hypertensive subjects without rebound effect throughout the 10-week clinical trial.
Several animal studies and a number of small human clinical trials have reported that consumption of bonito peptide can modestly reduce systolic and diastolic blood pressure in individuals with mild or moderate hypertension.
The pivotal clinical study of the Katsuobushi oligopeptide (KO) was published in a peer-reviewed journal (Fujita et al., 2001) and assessed both hypertensive rats and human subjects. The biofunctional peptide LKPNM was shown to significantly reduce systolic blood pressure in mildly hypertensive subjects in this work.
A 2019 randomized, crossover, placebo-controlled trial investigated acute cardiovascular effects. Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and this study investigated acute effects of a single dose of cholecalciferol (VitD3), bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. The randomized crossover placebo-controlled trial was conducted in 22 adults, who ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3 g of BPH, a combination of both, or a placebo.
Although clinical trials of food-protein-derived peptides in the management of hypertension have been published, the results are controversial. A meta-analysis searched for studies published between 2010 and 2021 and selected 12 eligible studies. The pooled effect of peptide intervention for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was −3.28 mmHg (95% CI: −4.54, −2.03, p < 0.001) and −1.82 mmHg (95% CI: −3.46, −0.18, p = 0.03), respectively.
Sub-group analyses showed that the reduction in BP in participants with higher basal BP (>140/85 mmHg) was greater, and the effect was stronger in Asian participants compared with non-Asian participants. Additionally, the effect of peptide intervention was more pronounced on SBP in participant groups with a lower ratio of male to female (≤0.5) and in participants with a mean age ≥50 years.
In conclusion, food-protein-derived antihypertensive peptides can significantly reduce BP in prehypertensive and hypertensive patients.
The overall body of human clinical evidence for bonito peptide's blood pressure-lowering effect is moderate. Most studies are small and short-term, and there is a need for larger, long-term trials to confirm both efficacy and safety. The mechanism is biochemically plausible and well-characterized, and Japan's FOSHU approval represents an important regulatory endorsement. However, no major Western regulatory body (such as the U.S. FDA or the European EFSA) has issued a positive health claim opinion for bonito peptide specifically.
The European Food Safety Authority (EFSA) reviewed a health claim related to bonito protein peptide and maintenance of normal blood pressure (ID 1716) under Article 13(1) of Regulation (EC) No 1924/2006. The supporting evidence cited in the EFSA dossier included human volunteer studies on the antihypertensive effect of katsuobushi oligopeptide, including placebo-controlled studies evaluating the effect of "peptide soup" on blood pressure in borderline and hypertensive subjects. The full outcome of this opinion placed it in a category requiring further scientific substantiation, consistent with EFSA's generally stringent approach to food-derived peptide health claims.
A distinct preparation — bonito fish-derived elastin peptide (VGPG Elastin®) — has been evaluated in a human clinical trial for skin-aging outcomes.
Recent in vitro and in vivo studies have suggested that elastin peptide improves the skin's biophysical properties, enhancing the proliferation of fibroblasts and elastin synthesis, resulting in anti-aging properties. Accordingly, a randomized, double-blinded, placebo-controlled study was conducted to clinically evaluate the effect of elastin peptide intake on human skin.
Healthy adult participants (N = 100) were randomly assigned to receive a test product containing 100 mg of bonito elastin peptide (VGPG Elastin®) or placebo. All participants were Asian from Korea. The parameters of skin wrinkles, hydration, and brightening (melanin index) were measured at baseline and 4, 8, and 12 weeks after intervention.
The average skin roughness, maximum peak-to-valley values, maximum peak height of the wrinkle, maximum valley depth, average maximum height, and eye wrinkle volume improved considerably in the test group compared with the placebo after 12 weeks of intervention. Skin hydration was enhanced, and the melanin index was significantly lower in the test group. No participant experienced adverse events related to the test product.
Oral consumption of bonito elastin peptide (VGPG Elastin®) reduced fine wrinkles, enhanced skin moisture, and decreased melanin index without significant adverse effects.
Evidence strength: Only a few clinical trials have evaluated the efficacy of oral elastin peptide supplementation. The skin-health evidence is therefore preliminary, resting primarily on a single randomized controlled trial conducted in a single Asian population.
The condensed fermentative extract of bonito (BoE), skipjack tuna (Katsuwonus pelamis), has been studied for health conditioning effects against lifestyle-related diseases such as hypertension and type 2 diabetes.
Antiobesity and anti-inflammatory effects of BoE were evaluated in mice fed a high-fat diet (HFD). Mice (9 weeks of age) were maintained for 11 weeks on HFD with or without BoE at doses of 50 mg or 500 mg/kg.
Compared with untreated mice, BoE-fed mice achieved maximum weight reductions of 7.4% (males) and 11.4% (females), and visceral fat in male high-dose mice was significantly decreased. Furthermore, an antiobesity gene uncoupling protein-1 was significantly induced in the visceral fat tissues of treated mice.
The antiobesity and anti-inflammatory effects of BoE were demonstrated in this animal examination system, and any toxic adverse effects were not observed in mice during the 3-month investigation.
Evidence strength: The antiobesity and anti-inflammatory effects are supported by animal data only. No published human clinical trials addressing these specific outcomes for bonito peptide were identified. These findings are preliminary and cannot be directly extrapolated to humans.
Bonito peptide powders refined and processed from the muscles of deep-sea skipjack tuna contain abundant anserine and carnosine. These dipeptides were shown to have hypouricemic activity with no undesirable side effects.
In studies on peptides associated with hyperuricemia, pelagic fishes such as tuna and bonito have been found to migrate at high speeds without causing an acid build-up in the body, a phenomenon attributed to the presence of the dipeptide anserine, which has become a new target for dietary intervention in hyperuricemia.
Previous research has demonstrated that bonito peptides had functions of antioxidant activity, reducing uric acid, and inhibiting xanthine oxidase (XOD).
Evidence strength: The evidence for bonito peptide's effect on uric acid is largely preclinical, based primarily on in vitro and animal models. Human clinical data in this area are sparse and insufficient to draw definitive conclusions.
Research shows that oligopeptides powder of marine fish can promote skin wound healing, eliminate inflammatory response, and has vasorelaxation, cholesterol-reducing, and antioxidative effects.
In studies of bonito hydrolysate fractions, peptides with a molecular weight cutoff of 600–1000 Da exhibited the highest antioxidant and xanthine oxidase-inhibitory activities.
Evidence strength: Antioxidant effects are supported by in vitro and animal studies. The evidence does not yet include high-quality human randomized controlled trials specifically designed to assess antioxidant biomarkers from bonito peptide supplementation.
Fish contains high quality proteins and essential nutrients. Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and studies have shown an association between relevant nutritional deficiencies, CVD, and CVD risk factors such as diabetes. The 2019 RCT evaluating bonito fish peptide hydrolysate (BPH) examined acute gene expression changes to explore mechanistic pathways relevant to cardiometabolic health, though longer-term intervention trials are required.
The following dosages are reported directly from identified sources and are presented as literature data only:
Bonito extract also contains relatively high amounts of sodium chloride (300 mg/g) and arsenic (23 ppm) that might cause adverse effects on health. These compounds are associated with multiple adverse effects including neurotoxicity and carcinogenicity. This concern applies specifically to condensed bonito extract (BoE) rather than to purified peptide isolates such as LKPNM, and is an important consideration for whole-extract preparations.
Bonito peptide is not acceptable for individuals with fish allergies. As a fish-derived protein hydrolysate, bonito peptide retains the potential to trigger allergic responses in individuals sensitized to fish proteins. The extent to which the hydrolysis process reduces allergenicity varies by preparation and has not been comprehensively characterized in safety studies.
Patients already taking ACE inhibitors or ARBs (angiotensin receptor blockers) show minimal added benefit from dietary peptides — approximately 1.2 mmHg difference versus placebo — because both act on the same enzymatic pathway. This shared mechanism implies that combining bonito peptides with pharmaceutical ACE inhibitors targets the same physiological step and is unlikely to provide additive blood pressure reduction. Whether this overlap could under any circumstances potentiate hypotensive effects requires further investigation in clinical populations.
In the 12-week randomized controlled trial of bonito elastin peptide, no participant experienced adverse events related to the test product. Similarly, in the animal study examining antiobesity and anti-inflammatory effects of BoE, no toxic adverse effects were observed in mice during the 3-month investigation.
Several Food for Specified Health Use (FOSHU) products containing fish protein hydrolysates/peptides as functional ingredients have been approved in Japan, and many of these products claim to be suitable for consumption by individuals with mild hypertension. No equivalent positive approval for a blood-pressure health claim for bonito protein peptide specifically has been identified from the FDA or EFSA.
Health conditions that Bonito peptide may help support.
Body systems that Bonito peptide may help support.
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