Anserine

• Antioxidant protection
• Cognitive function support
• Exercise performance enhancement

• pH buffering in muscles
• Anti-glycation effects
• Neuroprotection
• Immune modulation

Anserine (β-alanyl-1-methyl-L-histidine) is a naturally occurring dipeptide that is structurally similar to carnosine (β-alanyl-L-histidine), differing only by the methylation of the histidine residue. This methylation confers important functional differences, particularly in terms of stability and bioavailability. Anserine’s mechanisms of action are multifaceted and include: 1) Antioxidant activity: Anserine acts as a direct scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS), particularly hydroxyl radicals, peroxyl radicals, and peroxynitrite. The imidazole ring of the methylated histidine residue serves as the primary site for this antioxidant activity.

Additionally, anserine can chelate transition metals like copper and zinc, preventing them from catalyzing oxidative reactions. 2) pH buffering: Like carnosine, anserine functions as an intracellular buffer due to the imidazole group’s pKa value (approximately 7.0), which is close to physiological pH. This buffering capacity is particularly important in skeletal muscle during high-intensity exercise, where it helps maintain optimal pH for enzyme function and delays fatigue by neutralizing lactic acid accumulation. 3) Anti-glycation effects: Anserine inhibits the formation of advanced glycation end products (AGEs) by reacting with reactive carbonyl species, preventing them from modifying proteins and lipids.

This may contribute to its potential anti-aging effects and role in preventing diabetic complications. 4) Carnosinase resistance: A key advantage of anserine over carnosine is its greater resistance to degradation by serum carnosinase-1 (CN1), the enzyme that rapidly hydrolyzes carnosine in human plasma. The methylation of the histidine residue sterically hinders the binding of anserine to CN1, resulting in a longer half-life in circulation and potentially enhanced bioavailability to tissues. 5) Cognitive function support: Anserine may protect neurons through multiple mechanisms, including antioxidant effects, metal chelation, and anti-glycation properties.

Studies suggest it may help maintain cognitive function in aging populations, particularly when combined with carnosine. 6) Exercise performance enhancement: Anserine’s pH buffering capacity and antioxidant properties may contribute to improved high-intensity exercise performance by delaying muscle fatigue and protecting against exercise-induced oxidative stress. 7) Immune modulation: Some research suggests anserine may influence immune function through anti-inflammatory effects and modulation of cytokine production, though this area requires further investigation. 8) Potential metabolic effects: Emerging evidence suggests anserine may influence glucose metabolism and insulin sensitivity, possibly through protection of pancreatic β-cells from oxidative stress and glycation damage.

The combination of these mechanisms makes anserine a compound of interest for various applications, from sports nutrition to healthy aging support. Its enhanced stability compared to carnosine makes it particularly interesting as a dietary supplement, especially when the two dipeptides are combined to potentially provide complementary benefits.

The effective dosage range for anserine is not as well-established as for some other supplements due to limited human clinical trials focusing specifically on anserine alone. Most research has examined anserine in combination with carnosine. Based on available studies, effective doses appear to range from 300-1500 mg per day of combined anserine and carnosine, with anserine typically comprising the larger portion (often in a 2:1 or 3:1 ratio of anserine to carnosine). For acute performance enhancement, higher doses (25-30 mg/kg of body weight) have been studied, particularly when combined with carnosine in equal amounts.

For chronic supplementation targeting cognitive benefits or general health, lower daily doses (300-600 mg) have shown promising results in preliminary studies.

Anserine is absorbed from the gastrointestinal tract primarily via peptide transporters (PEPT1) in the small intestine. As a dipeptide, it can be absorbed intact, though some hydrolysis to its constituent amino acids (β-alanine and 1-methylhistidine) may occur in the intestinal lumen. Following oral administration, anserine reaches peak plasma concentrations within approximately 30-90 minutes, with considerable individual variation. A key advantage of anserine over carnosine is its greater resistance to serum carnosinase-1 (CN1), the enzyme that rapidly hydrolyzes carnosine in human plasma.

The methylation of the histidine residue in anserine sterically hinders its binding to CN1, resulting in a longer half-life in circulation (approximately 2-4 hours compared to less than 1 hour for carnosine). This enhanced stability contributes to anserine’s potentially greater bioavailability to tissues. However, anserine is still eventually metabolized, primarily by tissue carnosinase (CN2), with the resulting amino acids either utilized for protein synthesis, further metabolized, or excreted. The methylhistidine component is primarily excreted unchanged in urine, making it a useful biomarker for anserine consumption.

Combination with carnosine: When anserine and carnosine are co-administered, they may compete for the same degradation enzymes, potentially extending the half-life of both compounds. This competitive inhibition effect is the basis for many commercial formulations that combine these dipeptides., Fasted state administration: Taking anserine on an empty stomach may enhance absorption by reducing competition with dietary peptides for intestinal transporters., Carnosinase inhibitors: Theoretical approaches include combining anserine with compounds that further inhibit carnosinase activity, though commercial products specifically designed for this purpose are limited., Sustained-release formulations: Some specialized formulations aim to provide gradual release of anserine to maintain more consistent blood levels, though clinical evidence for enhanced efficacy is limited., Zinc supplementation: Some research suggests zinc may inhibit carnosinase activity, potentially enhancing anserine bioavailability, though this approach requires further investigation.

For cognitive benefits, consistent daily supplementation appears more important than specific timing, with most studies administering anserine (typically combined with carnosine) with meals to reduce potential gastrointestinal discomfort. For exercise performance enhancement, acute pre-exercise supplementation appears effective, with optimal timing approximately 30-60 minutes before high-intensity activity to allow for peak plasma concentrations during exercise. This timing aligns with studies showing improved performance in Wingate tests and other high-intensity exercises. When used for general health and antioxidant support, anserine can be taken with meals once or twice daily, with consistent long-term use likely more important than specific timing.

If taking multiple supplements, separating anserine from zinc supplements by at least 2 hours may be beneficial, as zinc could potentially affect absorption through various mechanisms, though direct evidence for this interaction is limited. For individuals with sensitive stomachs, taking anserine with food may reduce the potential for gastrointestinal discomfort, though this may slightly delay peak plasma concentrations.

• Mild gastrointestinal discomfort (uncommon)
• Nausea (rare)
• Headache (rare)
• Transient paresthesia (tingling sensation, very rare)
• Altered sense of smell or taste (very rare)

• Known hypersensitivity to anserine or related dipeptides
• Pregnancy and breastfeeding (due to insufficient safety data)
• Severe renal impairment (theoretical concern due to altered dipeptide metabolism)
• Children under 18 years (insufficient safety data)
• Individuals scheduled for surgery within two weeks (precautionary due to limited research)

• No well-documented drug interactions specific to anserine have been reported
• Theoretical interaction with medications affected by histidine metabolism, though clinical significance is unknown
• Potential additive effects with other antioxidant compounds, though generally considered beneficial rather than adverse
• Medications that affect renal function may theoretically influence anserine excretion, though clinical significance is unknown
• Zinc-containing supplements may potentially affect absorption if taken simultaneously, though direct evidence is limited

No established upper limit by major regulatory bodies. Most clinical studies have used doses ranging from 300-1500 mg daily without significant adverse effects. Acute studies have used higher doses (up to 30 mg/kg body weight) without reported safety concerns. Anserine is naturally present in the human diet, particularly in poultry and fish, suggesting good safety at typical supplemental doses.

The methylation of the histidine residue in anserine appears to enhance its stability and potentially its safety profile compared to carnosine. Long-term safety studies beyond 6 months are limited, though the compound’s presence as a natural dietary component suggests low risk with extended use. Based on available evidence, anserine appears to have a favorable safety profile, with no serious adverse effects reported in clinical trials. As with any supplement, individuals with pre-existing health conditions or those taking medications should consult healthcare providers before use.

Anserine does not have specific regulatory approval from the FDA as a drug or medical treatment. In the United States, anserine is typically marketed as a dietary supplement ingredient under the Dietary Supplement Health and Education Act (DSHEA) of 1994. As a supplement ingredient, anserine is subject to the general regulations governing dietary supplements, which require manufacturers to ensure safety but do not require pre-market approval. The FDA has not established a recommended daily allowance (RDA) or tolerable upper intake level (UL) for anserine.

Manufacturers of anserine-containing supplements must comply with Good Manufacturing Practices (GMPs) and are prohibited from making specific disease treatment or prevention claims. Allowable structure/function claims must be accompanied by the standard FDA disclaimer that the statements have not been evaluated by the FDA and that the product is not intended to diagnose, treat, cure, or prevent any disease. Anserine is naturally present in commonly consumed foods like chicken and fish, which contributes to its general recognition as safe (GRAS) status when used in supplements at levels comparable to dietary intake.

The European Food Safety Authority (EFSA) has not issued specific regulations or health claims approvals for anserine as a supplement ingredient. In the European Union, anserine would typically be regulated under the framework for food supplements (Directive 2002/46/EC). No approved health claims exist specifically for anserine under the EU Nutrition and Health Claims Regulation (EC) No 1924/2006. Manufacturers wishing to make health claims for anserine would need to submit scientific evidence for evaluation by EFSA.

As a naturally occurring component of commonly consumed foods, anserine is generally considered safe for use in food supplements, though specific maximum levels have not been established. Novel food authorization would not typically be required for anserine derived from traditional food sources, but synthetic forms or highly concentrated extracts might potentially fall under novel food regulations depending on the specific production method and history of use.

Health Canada does not have specific regulations for anserine as an isolated ingredient. In Canada, anserine-containing supplements would typically be regulated as Natural Health Products (NHPs) under the Natural Health Products Regulations. To be legally sold in Canada, such products would require a Natural Product Number (NPN), which involves assessment of safety, efficacy, and quality. Health Canada has not established specific monographs or recommended intake levels for anserine.

Manufacturers must provide evidence to support the safety and any claimed benefits of anserine-containing products as part of the product licensing process. As with other jurisdictions, the natural presence of anserine in commonly consumed foods like chicken and fish contributes to its general recognition as safe when used in supplements at comparable levels.

The Therapeutic Goods Administration (TGA) of Australia has not issued specific regulations for anserine as a supplement ingredient. In Australia, anserine-containing products would typically be regulated as complementary medicines under the Therapeutic Goods Act. Such products must be included in the Australian Register of Therapeutic Goods (ARTG) before they can be marketed. The TGA has not established specific recommended intake levels or maximum limits for anserine.

Manufacturers must provide evidence to support the safety and any claimed benefits of anserine-containing products as part of the listing or registration process. As in other jurisdictions, the natural presence of anserine in commonly consumed foods contributes to its general recognition as safe for use in supplements at comparable levels.

Japan: Anserine has received more regulatory attention in Japan than in many other countries, reflecting the greater market presence of anserine-containing supplements. The Japanese Ministry of Health, Labour and Welfare regulates anserine-containing products under the Foods with Health Claims system, which includes Foods for Specified Health Uses (FOSHU) and Foods with Function Claims (FFC). Several anserine-containing products have received approval for specific health claims in Japan, particularly related to blood pressure management and exercise recovery. China: In China, anserine-containing supplements would typically be regulated under the framework for health food products by the National Medical Products Administration (NMPA).

Specific approved health claims for anserine are limited. South Korea: The Korean Ministry of Food and Drug Safety (MFDS) regulates anserine-containing products as health functional foods. As in Japan, there is relatively greater market presence and regulatory recognition of anserine in South Korea compared to Western markets. European variations: Within Europe, there are some variations in how member states implement EU regulations for food supplements, which may affect the specific requirements for anserine-containing products in different countries.

Developing markets: In many developing countries, regulatory frameworks for supplements are still evolving, and specific regulations for anserine may be limited or absent.

Anserine is not available as a prescription medication in any major jurisdiction. It is sold exclusively as a non-prescription dietary or food supplement. No prescription requirements exist for anserine-containing supplements in the United States, European Union, Canada, Australia, Japan, or other major markets. The non-prescription status reflects its presence in the normal diet and generally recognized safety profile at typical supplemental doses.

While anserine itself does not require a prescription, consumers with medical conditions or those taking medications should consult healthcare providers before using anserine supplements, as is generally recommended for any dietary supplement.

Pure anserine supplements are relatively uncommon in the market, with most commercial products combining anserine with carnosine and sometimes other ingredients. Combined anserine/carnosine supplements typically range from $30-$80 for a 30-day supply, depending on dosage, brand reputation, and additional ingredients. Japanese chicken extract supplements containing standardized amounts of anserine tend to be at the higher end of this range, often $50-$90 for a month’s supply. Research-grade pure anserine for laboratory use is considerably more expensive, typically $200-$500 per gram, reflecting the specialized production and limited market.

Some sports nutrition products containing anserine as part of a broader formula range from $40-$100 for a 30-day supply, though the anserine content in these products is often lower than in dedicated anserine/carnosine supplements. The price of anserine supplements has remained relatively stable in recent years, though specialized formulations with clinical research backing tend to command premium prices.

Compared to other cognitive support supplements: Anserine/carnosine combinations are moderately expensive compared to basic cognitive supplements like B vitamins or generic ginkgo biloba, but less expensive than premium nootropic stacks or patented formulations. The specific mechanism of action and research in elderly populations may justify the higher cost for those specifically concerned with age-related cognitive changes. Compared to other exercise performance supplements: For acute performance enhancement, anserine/carnosine supplements are more expensive than basic supplements like creatine or beta-alanine, but comparable to premium pre-workout formulations. The research on specific performance benefits is still emerging, making value assessment challenging.

Compared to obtaining anserine from food sources: Dietary sources of anserine (primarily poultry and fish) provide the compound at a lower cost than supplements, but achieving the doses used in clinical studies would require consuming large amounts of these foods daily. For example, to obtain 500 mg of anserine would require approximately 250-500g of chicken breast, depending on the specific content. For those already consuming a diet rich in poultry and fish, supplementation may provide less additional value. Overall value consideration: The value proposition of anserine supplements is strongest for: 1) Older adults concerned about cognitive function, particularly those with APOE4 genotype based on some research; 2) Athletes seeking acute performance enhancement for high-intensity activities; 3) Individuals with limited consumption of anserine-rich foods (e.g., vegetarians who occasionally consume fish but not poultry).

Bulk purchasing options for anserine supplements are limited compared to more mainstream supplements. Some manufacturers offer modest discounts (typically 10-15%) for purchasing multiple bottles at once. Subscription services from some brands provide recurring shipments at a discount of approximately 10-20% compared to one-time purchases. Professional-grade supplement suppliers sometimes offer larger package sizes with better per-dose pricing for healthcare practitioners, though these are not typically available to general consumers.

Due to the relatively specialized nature of anserine supplements and limited number of manufacturers, significant bulk discounts are less common than for more commoditized supplements.

Anserine supplements are generally not covered by conventional health insurance plans in most countries. In the United States, anserine supplements may be eligible expenses for Health Savings Accounts (HSAs) or Flexible Spending Accounts (FSAs) if prescribed by a healthcare provider for a specific medical condition, though this is uncommon in practice. Some Japanese health insurance plans may provide partial coverage for specific anserine-containing products that have received FOSHU (Foods for Specified Health Uses) approval, though this varies by plan. Certain specialized healthcare plans focused on preventive medicine or integrative health may offer limited reimbursement for supplements including anserine when recommended by an in-network provider, but this is the exception rather than the rule.

Medicare, Medicaid, and most national healthcare systems do not cover anserine or other dietary supplements unless they are prescribed as medical foods for specific conditions, which is not typically the case for anserine.

Pure anserine in powder form, when properly stored, typically has a shelf life of 2-3 years. Commercial anserine supplements, which are often combined with carnosine and/or other ingredients, generally carry expiration dates of 1-2 years from the date of manufacture. The methylation of the histidine residue in anserine provides greater stability compared to carnosine, particularly in terms of resistance to enzymatic degradation. However, this structural modification does not completely protect against all degradation pathways, particularly those involving oxidation or hydrolysis.

Liquid formulations containing anserine have significantly shorter shelf lives, typically 6-12 months when unopened and 1-3 months after opening, depending on preservatives and storage conditions. Stability studies specifically on anserine are limited compared to more common supplements, and most commercial products base their shelf life on general stability testing of the complete formulation rather than isolated anserine.

Store in a cool, dry place, ideally between 15-25°C (59-77°F)., Protect from direct sunlight and UV radiation, which can accelerate degradation., Keep container tightly closed to protect from moisture and oxygen exposure., Avoid storage in bathrooms or other high-humidity environments., For liquid formulations, refrigeration after opening is often recommended., Some manufacturers recommend refrigeration for powder forms as well, particularly in hot and humid climates., Avoid freezing liquid formulations unless specifically recommended by the manufacturer., Keep away from strong-smelling substances, as anserine powder may absorb odors.

Moisture: Exposure to humidity can promote hydrolysis of the peptide bond., Heat: Elevated temperatures accelerate most degradation reactions., Light: UV and visible light can catalyze oxidation reactions., Oxygen: Promotes oxidation of the imidazole ring in the methylhistidine residue., pH extremes: Anserine is most stable at slightly acidic to neutral pH (approximately 5-7)., Metal ions: Certain transition metals can catalyze oxidation reactions., Enzymatic degradation: While more resistant than carnosine to carnosinase-1, anserine can still be degraded by tissue carnosinase (CN2) and other peptidases., Microbial contamination: Can lead to enzymatic degradation and production of potentially harmful metabolites.

Anserine shows moderate stability in aqueous solution, with greater stability than carnosine due to the methylation of the histidine residue, which provides some protection against enzymatic degradation. In neutral aqueous solutions at room temperature, anserine typically remains stable for several days to weeks, depending on other conditions such as light exposure and the presence of metal ions or preservatives. Stability is enhanced in slightly acidic solutions (pH 5-6) and reduced in alkaline conditions. The addition of antioxidants such as vitamin C or vitamin E can improve stability by protecting against oxidation of the imidazole ring.

Solutions containing anserine should ideally be stored in amber or opaque containers to protect from light-induced degradation. Refrigeration significantly extends the stability of anserine in solution, potentially doubling or tripling its shelf life compared to room temperature storage. For research applications requiring maximum stability, anserine solutions can be prepared in buffer systems containing chelating agents (to bind metal ions) and stored under nitrogen or argon to minimize oxidation. In commercial liquid formulations, various preservatives and stabilizers are typically added to extend shelf life, though specific formulation details are often proprietary.

Natural Sources

Synthetic Production Methods

Quality Indicators

Sustainability Considerations

Unlike many other supplements with long histories of traditional use, anserine does not have documented traditional applications as an isolated compound. This is primarily because anserine was not identified or characterized until the 20th century, and its presence in foods was not recognized in traditional medicine systems. However, the foods rich in anserine, particularly poultry and fish, have been valued in various traditional medicine systems for their health benefits. In Traditional Chinese Medicine, chicken soup (now known to contain significant amounts of anserine) has been prescribed for centuries to strengthen vital energy (qi) and support immune function.

Similarly, in European folk medicine, chicken broth was traditionally used for convalescence and recovery from illness. In Japanese traditional diet, fish consumption has been associated with longevity and cognitive health, benefits that may be partially attributable to histidine dipeptides like anserine. While these traditional uses did not specifically identify anserine as the active component, they represent historical recognition of the health benefits of anserine-rich foods. It’s worth noting that traditional processing methods for meat and fish, such as certain forms of cooking, curing, or fermentation, may have inadvertently preserved or enhanced the bioavailability of naturally occurring anserine, though this was not done with specific knowledge of the compound.

Anserine was first isolated and identified in 1929 by the Japanese chemist Yoshimasa Endo from goose muscle extract (the name ‘anserine’ derives from Anser, the genus name for geese). Initially, it was characterized as a histidine-containing compound similar to carnosine, which had been discovered earlier in 1900 by the Russian chemist Vladimir Gulevich. The complete chemical structure of anserine as β-alanyl-1-methyl-L-histidine was elucidated in the 1940s, revealing it to be a methylated derivative of carnosine. Early research focused primarily on its biochemical properties and distribution in animal tissues, with studies in the 1950s and 1960s establishing its high concentration in the muscles of birds and certain fish.

The physiological functions of anserine began to be investigated more thoroughly in the 1970s and 1980s, with research demonstrating its antioxidant properties, pH buffering capacity, and metal-chelating abilities. A significant breakthrough in understanding anserine’s potential advantages over carnosine came in the 1990s and early 2000s, when researchers discovered its greater resistance to degradation by serum carnosinase, the enzyme that rapidly breaks down carnosine in human blood. This finding suggested that anserine might have greater bioavailability and potentially more significant physiological effects when consumed as a supplement. The 2010s saw increased interest in anserine’s potential cognitive benefits, particularly through research in Japan led by scientists like Tatsuhiro Hisatsune, whose work demonstrated potential benefits of anserine/carnosine supplementation for cognitive function in elderly adults.

The evolution of anserine as a supplement is relatively recent compared to many other nutritional compounds. Until the late 20th century, anserine was primarily of interest to biochemists and physiologists rather than being used as a dietary supplement. The first commercial applications of anserine emerged in Japan in the 1990s, primarily in the form of chicken extract supplements that naturally contained both anserine and carnosine. These products were marketed for general health and vitality rather than for specific health conditions.

The early 2000s saw the development of more targeted supplements containing standardized amounts of anserine, often in combination with carnosine. These were initially marketed for sports performance, based on the compounds’ roles in muscle buffering and antioxidant protection. By the 2010s, research on cognitive benefits led to a shift in marketing focus, with many anserine-containing supplements being positioned for healthy brain aging and cognitive support, particularly in Asian markets. The publication of clinical studies showing potential cognitive benefits in elderly populations, especially those with mild cognitive impairment, further expanded interest in anserine supplementation for brain health.

Current usage continues to evolve, with ongoing research exploring applications in metabolic health, exercise recovery, and various aspects of healthy aging. Most commercial formulations still combine anserine with carnosine, based on research suggesting synergistic effects when the compounds are co-administered. Despite growing interest, anserine remains less well-known than many other supplements in Western markets, though awareness is increasing as research on its potential benefits continues to expand. The evolution of anserine supplementation represents an interesting case study in how modern scientific research can identify and develop applications for naturally occurring compounds that were not specifically recognized in traditional medicine systems.

AEQUIP (Anserine/Carnosine Supplementation for Improved Cognition) follow-up studies examining longer-term cognitive effects in various populations, Investigations of anserine/carnosine supplementation for cognitive support in specific neurodegenerative conditions, Studies examining the potential of anserine supplementation for metabolic health and insulin sensitivity, Research on optimal dosing strategies for athletic performance enhancement, Comparative studies of different histidine dipeptides (anserine, carnosine, balenine) for various health applications