Home Ingredients Balenine (Ophidine, Imidazole Dipeptide)

Balenine (Ophidine, Imidazole Dipeptide)

Evidence Level
Preliminary
4 Clinical Trials
6 Documented Benefits
1/5 Evidence Score

Balenine, also called ophidine, is a small dipeptide made of beta-alanine and a methylated form of histidine. It is a relative of carnosine and anserine but a separate compound. It is abundant in whale muscle and in the opah fish, and the products studied in people include a Japanese whale meat extract, opah muscle extract and synthetic balenine powder. Its clearest human finding is about absorption: unlike carnosine and anserine, it resists the blood enzyme serum carnosinase, so it stays in the blood for hours after a single dose. That has not translated into measured benefits so far. A single pre-exercise dose did not improve sprint or time-trial performance, and the only longer trial, a 14-person study of a whale meat extract funded by its supplier, found no difference on standard memory tests and a gain on one work-speed test. Other findings come from animals and lab tests.

Studied Dose Single doses of 1, 4 and 10 mg per kg body weight of synthetic balenine in an absorption study, and 10 mg per kg before exercise in a 20-person trial. One 12-week trial used 2.5 g a day of whale meat extract supplying 195 mg of balenine. No established dose.
Active Compound Balenine (ophidine), beta-alanyl-N(tau)-methyl-L-histidine; IUPAC name beta-alanyl-1-methyl-L-histidine (PubChem CID 10198648, ChEBI 193825): beta-alanine joined to tau-methylhistidine. Older biochemical papers number that ring nitrogen 3 and write beta-alanyl-3-methyl-L-histidine, which under IUPAC numbering is the name of anserine (methyl on the other ring nitrogen, N(pi)). PubChem also files the name ophidine under anserine, so the structure, not the name, identifies balenine.

Benefits

Resistance to breakdown by the blood enzyme carnosinase (human study)

In human plasma, balenine lasted about 35 minutes before half was broken down, against about 1 to 2 minutes for carnosine and anserine. In 6 young adults, single oral doses of up to 10 mg per kg body weight raised plasma balenine for up to 8 hours, and about a quarter of the dose left the body intact in urine. This shows absorption, not a health effect.

Supported by Trial 1

Cycling sprint and time-trial performance after a single dose (human trial)

In 20 active recreational cyclists, 10 mg per kg body weight of synthetic balenine before testing did not improve sprint power, leg strength, or 4 km and 20 km time-trial times versus placebo, and did not change blood acidity markers or mental performance. Blood sugar stayed higher during and after the 20 km ride with balenine, a finding of unclear meaning.

Supported by Trial 2, Trial 1

Thinking test scores in older adults taking whale meat extract

In a 12-week placebo-controlled trial of 14 adults aged 60 to 79 who felt more forgetful, 2.5 g a day of whale meat extract (195 mg balenine) did not beat placebo on the MMSE, a blood-protein screen for cognitive decline risk or a mood scale. The authors report a gain on one work-speed test. The extract supplier funded it, and the journal is not PubMed-indexed.

Supported by Trial 3

Absorption from opah fish muscle and muscle extract (human study)

After people ate opah muscle extract (5 or 10 g) or 80 g of opah flesh, plasma balenine rose to peaks of about 82 to 152 nmol/mL, along with its building blocks beta-alanine and tau-methylhistidine (usually called 3-methylhistidine). Only the abstract could be checked, and it gives no participant numbers. It shows food balenine is absorbed, not that it does anything.

Supported by Trial 4

Muscle repair and memory tests in mice (animal studies)

In mice, a diet with a balenine-enriched extract sped up the repair stage after a toxin-induced muscle injury, in work co-authored by employees of a Japanese seafood company. In aging-prone mice, 26 weeks of a balenine-rich whale meat extract improved learning and memory tests. Both tested extracts, not pure balenine, and neither has been shown in people.

Supported by Trial 3, Trial 4

Antioxidant and iron-binding activity in lab tests

In test-tube assays, balenine purified from opah muscle showed higher antioxidant scores (ORAC and HORAC) and stronger binding of iron than carnosine or anserine at the same concentration. In human cell cultures it also lessened barrier damage caused by the reactive compound methylglyoxal. These are laboratory results only.

Supported by Trial 1, Trial 3

Mechanism of action

1

Methyl group shields it from carnosinase

Serum carnosinase rapidly splits carnosine in human blood. An older enzyme study found balenine and anserine were split 3 to 4 times more slowly than carnosine, and computer modeling shows the methyl group on balenine's imidazole ring weakens its fit in the enzyme's binding pocket. People with higher enzyme activity still clear it faster.

2

Proposed acid buffering in muscle

Carnosine, anserine and balenine have a chemical structure that suits them to buffer acid inside muscle, and animals that rely on bursts of energy without oxygen, such as diving whales, carry high levels. This comes from animal comparisons. In the one human exercise trial, balenine did not change blood pH, bicarbonate or lactate.

3

Antioxidant, metal-binding and carbonyl-quenching chemistry

Like its relatives, balenine showed antioxidant activity and bound iron in lab assays, and it protected cell barriers from methylglyoxal in culture. Whether oral doses do this in human tissues has not been measured.

Clinical trials

1
Balenine Absorption and Carnosinase Resistance in Humans
PubMed

Lab test of carnosine, anserine and balenine breakdown in human plasma, then an open dose-escalation pharmacokinetic study of single oral doses of synthetic balenine (1, 4 and 10 mg per kg body weight), not randomized and with no placebo. Balenine powder supplied by NNB Nutrition. (de Jager et al. 2023, Sci Rep)

6 healthy young adults (3 men, 3 women; one woman replaced for the last dose), mean age about 25.

Plasma half-life in the lab was about 35 minutes for balenine versus 1.2 minutes for carnosine and 2.1 minutes for anserine. After 10 mg per kg, plasma balenine peaked at 28 micromolar and stayed raised up to 8 hours; about 27% of the dose appeared intact in urine. Higher carnosinase activity went with lower blood levels. Absorption data only; no health outcome was measured.

2
Single Dose of Balenine and Cycling Performance: No Effect
PubMed

Placebo-controlled trial of 10 mg per kg body weight of synthetic balenine taken before cycling sprints, maximal leg contractions, and 4 km and 20 km time trials. (de Jager et al. 2023, Int J Sport Nutr Exerc Metab)

20 healthy, active recreational cyclists (14 men, 6 women).

Balenine did not improve peak power (p = .3553), peak torque (p = .3169), 4 km time (p = .8566) or 20 km time (p = .2660), and did not change pH, bicarbonate, lactate or mental performance. Blood glucose stayed higher during and after the 20 km time trial with balenine. Performance did not correlate with plasma balenine or carnosinase activity.

3
Whale Meat Extract and Thinking Tests in Older Adults (not PubMed-indexed, supplier-funded)
PubMed

Randomized, placebo-controlled, double-blind 12-week trial of 2.5 g a day of whale meat extract (Whale Extract B8, 195 mg balenine a day) or corn-starch placebo, funded by the extract supplier Kyodo Senpaku Co. Ltd.; registered UMIN000031366. (Hirabayashi et al. 2023, Biomed J Sci Tech Res)

14 adults aged 60 to 79 (7 per group) who felt their forgetfulness had increased; mean age about 73.

No significant difference from placebo on the MMSE, a blood-protein MCI screen or the Zung depression scale. The abstract and discussion report a significant gain over placebo on the Uchida-Kraepelin work-speed test at 12 weeks, but the results section says both groups improved and the between-group test is not clearly described. Salivary antioxidant potential fell with the extract and rose with placebo, significant at 6 weeks only. Exact p-values were mostly not reported, and adverse events were not reported.

4
Balenine Absorption After Eating Opah Fish Muscle or Extract (abstract only)
PubMed

Human absorption study measuring plasma balenine and its amino acids after eating opah muscle extract or opah flesh; design and participant numbers are not given in the abstract. (Shigemura et al. 2024, J Funct Foods)

Human volunteers (number not stated in the abstract).

Peak plasma balenine was about 90 nmol/mL after 5 g of opah muscle extract, 152 nmol/mL after 10 g, and 82 nmol/mL after 80 g of opah flesh, with rises in 3-methylhistidine and beta-alanine. Shows absorption from food; no health outcome was measured. Not PubMed-indexed.

Side effects and drug interactions

Common Potential side effects

The human safety record is very small: single doses in 6 and 20 healthy young adults and one 12-week trial in 14 older adults. The absorption study does not describe any adverse events, and the 12-week trial did not report on them.
Before the first human study, single doses of up to 2000 mg per kg body weight caused no pathological changes in 7 rats observed for 2 weeks. That is an animal screening test, not human safety data.
In one trial, blood sugar stayed higher during and after a 20 km cycling time trial after balenine than after placebo. The meaning of this is unclear.
Balenine extracts are made from fish (opah) or whale muscle. A single case report describes an IgE allergy with anaphylaxis to bowhead whale and seal meat, so people with fish, seafood or marine mammal allergies should check the source and ask a doctor.
Pregnancy and breastfeeding: there are no safety data for balenine supplements.

Important Drug interactions

No drug interactions have been studied or documented. People taking prescription medicines, including medicines that affect blood sugar, should check with a doctor or pharmacist before adding a concentrated supplement.

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Frequently asked questions about Balenine (Ophidine, Imidazole Dipeptide)

How is balenine different from anserine and carnosine?

All three are dipeptides of beta-alanine and histidine. Carnosine has no methyl group, while anserine and balenine each carry one on a different nitrogen of histidine's ring. That small change makes balenine much more resistant to the blood enzyme that breaks down carnosine and anserine within minutes, so it stays in the blood for hours. Anserine and carnosine have their own pages.

Where does balenine come from in food?

It is abundant in whale muscle and in the opah fish, and adult pig muscle can contain substantial amounts. It is only just detectable in human muscle. Studied products include whale and opah muscle extracts and synthetic balenine; the published human absorption and exercise studies used synthetic balenine.

Does balenine help exercise performance?

Not in the one trial that tested it. In 20 active cyclists, a single pre-exercise dose of 10 mg per kg body weight did not improve sprint power, strength or time-trial times compared with placebo, even though blood levels were similar to or higher than those seen with anserine.

Can whale meat extract be bought in the United States?

Under the US Marine Mammal Protection Act, marine mammal products generally cannot be imported into the United States except in limited permitted cases, and buying or selling a product taken in violation of the Act is also unlawful. Check the label for the source of any balenine product; fish (opah) extracts and synthetic balenine are the alternatives that have been studied.

What is Balenine?

Balenine, also called ophidine, is a small dipeptide made of beta-alanine and a methylated form of histidine. It is a relative of carnosine and anserine but a separate compound.

What is Balenine used for?

NutraSmarts does not list Balenine under a health category. What the research covers: In human plasma, balenine lasted about 35 minutes before half was broken down, against about 1 to 2 minutes for carnosine and anserine.

What is the recommended dosage of Balenine?

The clinically studied dose is Single doses of 1, 4 and 10 mg per kg body weight of synthetic balenine in an absorption study, and 10 mg per kg before exercise in a 20-person trial. One 12-week trial used 2.5 g a day of whale meat extract supplying 195 mg of balenine. No established dose. Always follow the product label and check with a healthcare provider for personal advice.

Is Balenine safe, and does it have side effects?

Side effects and cautions reported for Balenine include: The human safety record is very small: single doses in 6 and 20 healthy young adults and one 12-week trial in 14 older adults. The absorption study does not describe any adverse events, and the 12-week trial did not report on them. It may also interact with some medications. Balenine is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Balenine interact with any medications?

Possible interactions include: No drug interactions have been studied or documented. People taking prescription medicines, including medicines that affect blood sugar, should check with a doctor or pharmacist before adding a concentrated supplement. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Balenine?

NutraSmarts rates the evidence for Balenine as Preliminary (1 out of 5). It is backed by 4 study summaries and 16 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(16 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. de Jager S, Vermeulen A, De Baere S, Van der Stede T, Lievens E, Croubels S, Jäger R, Purpura M, Bourgois JG, Derave W. Acute balenine supplementation in humans as a natural carnosinase-resistant alternative to carnosine. Sci Rep. 2023;13(1):6484. doi: 10.1038/s41598-023-33300-1.PubMedUsed to support: In human plasma in the lab, balenine had a half-life of about 35 minutes versus about 1.2 minutes for carnosine and 2.1 minutes for anserine. Six young adults then took rising single oral doses of synthetic balenine (1, 4 and 10 mg per kg body weight). The 10 mg per kg dose gave a peak plasma level of 28 micromolar, plasma stayed raised for up to 8 hours, and about 27% of the dose was excreted intact in urine (versus about 6% for anserine in an earlier study). People with higher carnosinase activity reached lower levels. The balenine powder was supplied by NNB Nutrition; the authors declared no competing interests, although two co-authors (Jäger R, Purpura M) list Increnovo LLC as their affiliation.
  2. de Jager S, Van Damme S, De Baere S, Croubels S, Jäger R, Purpura M, Lievens E, Bourgois JG, Derave W. No Effect of Acute Balenine Supplementation on Maximal and Submaximal Exercise Performance in Recreational Cyclists. Int J Sport Nutr Exerc Metab. 2023;33(2):84-92. doi: 10.1123/ijsnem.2022-0115.PubMedUsed to support: 20 healthy, active volunteers (14 men, 6 women) took 10 mg per kg body weight of balenine or placebo before testing. Balenine did not improve sprint peak power, peak torque, or 4 km or 20 km time-trial times, and did not change blood pH, bicarbonate, lactate or mental performance. Blood glucose stayed higher during and after the 20 km time trial with balenine. Performance did not correlate with plasma balenine or carnosinase activity.
  3. Hirabayashi T, Shibato J, Kimura A, Yamashita M, Takenoya F, Shioda S. Clinical Trial to Evaluate if Balenine, A Major Component of Whale Meat Extract, Improves Cognitive Function in Subjects with Symptoms of Increasing Forgetfulness Biomedical Journal of Scientific & Technical Research. 2023;49(2):40391-40400. doi: 10.26717/BJSTR.2023.49.007766.SourceUsed to support: Not PubMed-indexed (full text read on the publisher site). Randomized, placebo-controlled, double-blind 12-week trial in 14 adults aged 60 to 79 who felt their forgetfulness had increased (7 per group), using 2.5 g a day of a whale meat extract supplying 195 mg of balenine. The MMSE, a blood-protein MCI screen and a depression scale showed no significant difference from placebo. The abstract reports a significant gain over placebo on the Uchida-Kraepelin work-speed test at 12 weeks (the results text says both groups improved and does not clearly describe a between-group test), and salivary antioxidant potential fell with the extract versus placebo at 6 weeks. Funded by the extract supplier, Kyodo Senpaku Co. Ltd., which the paper says provided materials and had no role in design or conduct; a JSPS KAKENHI grant is also acknowledged; registered as UMIN000031366.
  4. Shigemura Y, Iwasaki Y, Hosokawa M, Arai Y, Seko T, Sawada R, Kawabata Y, Ishihara K. Absorption of food-derived balenine and its constituent amino acids in human plasma after ingestion of opah muscle and muscle extract in water Journal of Functional Foods. 2024;122:106521. doi: 10.1016/j.jff.2024.106521.SourceUsed to support: Not PubMed-indexed (abstract read). After people ate opah muscle extract (5 g or 10 g) or 80 g of opah flesh, plasma balenine peaked at about 90, 152 and 82 nmol/mL, and its building blocks 3-methylhistidine and beta-alanine also rose. The abstract does not give participant numbers or study design. Measures absorption only, not a health outcome.
  5. Jędrejko M, Kała K, Muszyńska B. Anserine, Balenine, and Ergothioneine: Impact of Histidine-Containing Compounds on Exercise Performance-A Narrative Review. Nutrients. 2025;17(5):828. doi: 10.3390/nu17050828.PubMedUsed to support: Narrative review of exercise studies. It describes balenine as a marine dipeptide with high content in whales and opah, found only one human exercise study of balenine (the 20-person cyclist trial, which used synthetic balenine and found no effect), and calls for human trials of natural sources such as standardized opah or whale extract.
  6. Pegova A, Abe H, Boldyrev A. Hydrolysis of carnosine and related compounds by mammalian carnosinases. Comp Biochem Physiol B Biochem Mol Biol. 2000;127(4):443-6. doi: 10.1016/s0305-0491(00)00279-0.PubMedUsed to support: Enzyme study with human serum and rat kidney carnosinase: carnosine was hydrolyzed 3 to 4 times faster than anserine and ophidine (balenine). The authors conclude that methylation of carnosine increases its resistance to enzymatic breakdown. Laboratory data.
  7. Toviwek B, Suwanasopee T, Koonawootrittriron S, Jattawa D, Pongprayoon P. Binding Modes of Carnostatine, Homocarnosine, and Ophidine to Human Carnosinase 1. ACS Omega. 2023;8(45):42966-42975. doi: 10.1021/acsomega.3c06139.PubMedUsed to support: Computer simulation (molecular dynamics) of ligands in human serum carnosinase (CN1): ophidine (balenine) showed the poorest binding affinity of the compounds tested, because its methylated imidazole ring disrupts the interaction network in the enzyme pocket. Modeling only.
  8. Harris CI, Milne G. The identification of the N tau-methyl histidine-containing dipeptide, balenine, in muscle extracts from various mammals and the chicken. Comp Biochem Physiol B. 1987;86(2):273-9. doi: 10.1016/0305-0491(87)90291-4.PubMedUsed to support: Identifies balenine as beta-alanyl-N tau-methyl histidine and finds it in muscle of 9 mammal species, including man, and the chicken. Levels varied widely: just detectable in human and rat muscle, up to 14 micromol per g wet muscle in adult pigs.
  9. Ishihara K, Watanabe R, Kato T, Seko T, Matsuda T, Omura Y, Shigemura Y, Kawabata Y, Maegawa T. Isolation of balenine from opah (Lampris megalopsis) muscle and comparison of antioxidant and iron-chelating activities with other major imidazole dipeptides. Food Chem. 2021;364:130343. doi: 10.1016/j.foodchem.2021.130343.PubMedUsed to support: Hot-water extraction and purification gave 41 g of over 95% pure balenine from 1 kg of opah muscle. In test-tube assays at 0.3 mM, opah balenine had higher ORAC and HORAC antioxidant values and iron(II)-chelating ability than carnosine and anserine. Two co-authors are from Kyokuyo Co. Ltd. Laboratory data.
  10. Shigemura Y, Iwasaki Y, Sato Y, Kato T, Seko T, Ishihara K. Detection of Balenine in Mouse Plasma after Administration of Opah-Derived Balenine by HPLC with PITC Pre-Column Derivatization. Foods. 2022;11(4):590. doi: 10.3390/foods11040590.PubMedUsed to support: Mouse study: 1 hour after opah-derived balenine was given, plasma balenine and 3-methylhistidine rose (to about 128 and 69 nmol/mL), while they were undetectable in control and carnosine-fed mice. Animal absorption data.
  11. Yang M, Sun L, Kawabata Y, Murayama F, Maegawa T, Nikawa T, Hirasaka K. Balenine, Imidazole Dipeptide Promotes Skeletal Muscle Regeneration by Regulating Phagocytosis Properties of Immune Cells. Mar Drugs. 2022;20(5):313. doi: 10.3390/md20050313.PubMedUsed to support: Mouse study: a diet with a balenine-enriched extract sped up the regeneration stage after toxin-induced muscle injury and raised regeneration-related gene markers, and balenine increased macrophage phagocytic activity in the lab. Three authors are employees of Kyokuyo Co., Ltd., which the paper says had no role in the study. Animal and cell data.
  12. Wada N, Yamanaka S, Shibato J, Rakwal R, Hirako S, Iizuka Y, Kim H, Matsumoto A, Kimura A, Takenoya F, Yasunaga G, Shioda S. Behavioral and omics analyses study on potential involvement of dipeptide balenine through supplementation in diet of senescence-accelerated mouse prone 8. Genom Data. 2016;10:38-50. doi: 10.1016/j.gdata.2016.09.004.PubMedUsed to support: Mouse study: senescence-accelerated SAMP8 mice fed a diet with balenine-rich whale meat extract for 26 weeks did better on learning and memory tests and showed shifts in brain gene expression versus controls. One author is from the Institute of Cetacean Research. The extract, not balenine alone, was tested. Animal data.
  13. Dolan E, Saunders B, Harris RC, Bicudo JEPW, Bishop DJ, Sale C, Gualano B. Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid-base regulation of skeletal muscle. Comp Biochem Physiol A Mol Integr Physiol. 2019;234:77-86. doi: 10.1016/j.cbpa.2019.04.017.PubMedUsed to support: Review of comparative physiology on carnosine, anserine and balenine: species that rely heavily on non-oxidative energy, including diving whales, sprinting racehorses and greyhounds, and chickens and turkeys, have high levels of these dipeptides, and their pKa suits them to buffering acid inside muscle. Evidence from animal comparisons, not supplement trials.
  14. Wetzel C, Gallenstein N, Peters V, Fleming T, Marinovic I, Bodenschatz A, Du Z, Küper K, Dallanoce C, Aldini G, Schmoch T, Brenner T, Weigand MA, Zarogiannis SG, Schmitt CP, Bartosova M. Histidine containing dipeptides protect epithelial and endothelial cell barriers from methylglyoxal induced injury. Sci Rep. 2024;14(1):26640. doi: 10.1038/s41598-024-77891-9.PubMedUsed to support: Cell-culture study in human kidney tubular and umbilical vein endothelial cells: carnosine, balenine and anserine each lessened the drop in barrier electrical resistance caused by the reactive compound methylglyoxal; carnosine and anserine also normalized transport and the tight-junction protein ZO-1. Laboratory data.
  15. Moore LM, Rathkopf MM, Sanner CJ, Whisman BA, Demain JG. Seal and whale meat: two newly recognized food allergies. Ann Allergy Asthma Immunol. 2007;98(1):92-6. doi: 10.1016/S1081-1206(10)60866-6.PubMedUsed to support: Case report of a boy with moderate anaphylaxis after eating bowhead whale and bearded seal meat, confirmed by specific IgE immunoblots and positive skin prick tests; described as the first reported case of specific IgE to these species.
  16. NOAA Fisheries. Marine Mammal Protection Act NOAA Fisheries (U.S. National Oceanic and Atmospheric Administration). 2026;Statute text: Sec. 101(a) moratorium on taking and importation; Sec. 102(a)(4) prohibition on transport, purchase and sale. Accessed 2026..SourceUsed to support: Not PubMed-indexed; official US government source. Under the Marine Mammal Protection Act moratorium, no marine mammal or marine mammal product may be imported into the United States except in limited cases, such as permits for scientific research or public display. The Act also makes it unlawful to transport, purchase or sell a marine mammal product taken in violation of the Act.