Anserine | Supplementopedia

Overview

Anserine (β‑N‑π‑carboxyethylhistidine) is a naturally occurring imidazole dipeptide composed of β‑alanine and 1‑methylhistidine.

Source: Found primarily in the skeletal muscle and brain of birds and fish.
Function: Acts as a potent antioxidant and metal‑chelating agent.
Use: Commonly used as a dietary supplement to support cognitive health and mitigate oxidative stress.

Research suggests anserine supplementation can:

Improve Cognitive Performance: Especially in tasks requiring attention and working memory, likely via reduced oxidative damage in the brain.
Enhance Muscle Endurance: Reduce exercise‑induced fatigue by buffering intracellular pH and limiting reactive oxygen species (ROS) accumulation.
Support Vascular Health: Attenuate endothelial inflammation and improve endothelial nitric‑oxide synthase (eNOS) activity, which may modestly improve blood pressure regulation.
Exhibit Anti-Glycation Effects: Potentially aiding glycemic control.
Clinical Trial Result: A 12‑week, double‑blind trial in older adults showed a 5‑10 % improvement in the “Trail‑Making Test” scores with 750 mg/day anserine plus carnosine versus placebo (Matsui et al., 2021).
Animal Study Result: Animal studies also demonstrate reduced muscle atrophy and preserved mitochondrial function with daily doses of 50–100 mg/kg.

Anserine acts as a “dual‑function” molecule:

Antioxidant Action: Its imidazole ring scavenges hydroxyl radicals and peroxynitrite, directly neutralizing ROS.
pH Buffering: The β‑alanine moiety supplies a buffer capacity that stabilizes intracellular pH during high-intensity contraction, similar to carnosine.
Metal Chelation (Brain): Chelates transition metals (Fe²⁺/Cu²⁺), limiting metal‑catalyzed Fenton reactions that generate ROS.
Anti-Glycation: Inhibits the formation of advanced glycation end-products (AGEs) by reacting with carbonyl groups on proteins, thereby preserving protein function.
Nrf2-ARE Pathway Activation: Up-regulates the Nrf2‑ARE pathway, increasing expression of antioxidant enzymes (e.g., superoxide‑dismutase, heme‑oxygenase‑1).
Akt-mTOR Axis Modulation: Modulates the Akt‑mTOR axis, promoting mitochondrial biogenesis and reducing apoptosis in neuronal and skeletal muscle cells.

Clinical studies have used oral anserine doses:

Dosage Range: Ranging from 250 mg to 1 g per day.
Combination: Often combined with 250 mg–500 mg of carnosine to exploit synergistic effects.
Cognitive Support: 500 mg once daily (preferably with a meal to enhance absorption) is the most common regimen; a 2‑week loading phase is not required.
Ergogenic Benefits (Athletes): 750 mg–1 g split into two doses (pre‑ and post‑exercise) to maintain plasma levels during training.
Elderly Population: 500 mg/day for 12–24 weeks has shown consistent cognitive benefits with minimal adverse events.
Renal Insufficiency: Reduce to 250 mg/day and monitor serum creatinine.
Dose-Response: No clear dose‑response curve beyond 1 g/day has been documented, and higher doses have not shown additional benefit.

Anserine is generally well‑tolerated:

Side Effects: Reported side effects are mild and include transient gastrointestinal discomfort (e.g., mild nausea) in <5 % of participants at doses >1 g/day.
Adverse Events: No serious adverse events have been reported in human trials up to 1 g/day for 12 months.
Contraindications: Severe renal impairment (eGFR < 30 mL/min/1.73 m²) because the dipeptide is cleared renally.
Caution: Advised when co-administered with high‑dose zinc or copper supplements, as anserine’s metal‑chelating properties could theoretically alter trace‑metal homeostasis.
Pregnancy/Lactation: Insufficient safety data; avoid supplementation or limit to ≤250 mg/day under medical supervision.
Drug Interactions: No known drug‑interaction alerts have been identified, but clinicians should monitor for additive antioxidant effects when combined with other strong antioxidants (e.g., high‑dose vitamin C/E).

Type: A dipeptide (β‑alanine‑1‑methyl‑histidine).
Molecular Formula: C₈H₁₅N₅O₃
Molecular Weight: 219.24 g·mol⁻¹
IUPAC Name: N‑β‑alanine‑1‑methyl‑L‑histidine
Structure: Consists of a β‑alanine (NH₂‑CH₂‑CH₂‑COOH) linked via an amide bond to a 1‑methyl‑histidine residue, giving the characteristic imidazole ring with a methyl group at the N1 position.
Charge: Zwitterionic at physiological pH.
pKa: ≈ 7.2, which confers its buffering capacity.
Solubility: Highly soluble in water (≈30 g/L at 25 °C).
Stability: Stable under neutral pH.
Hydrolysis: Susceptible to enzymatic hydrolysis by dipeptidases, which can be mitigated by encapsulation or co-administration with carnosine.

Source: Predominantly extracted from the skeletal muscle of poultry (especially chicken breast) and certain fish (e.g., tuna, mackerel).
Content: Can constitute up to 2 % of the total protein content.
Production: Commercial production often utilizes enzymatic hydrolysis of meat protein followed by solid‑phase extraction and high‑performance liquid chromatography (HPLC) purification to achieve >95 % purity.
Synthetic Route: Synthetic routes involve stepwise coupling of β‑alanine with protected 1‑methyl‑histidine, but this is less common due to cost.
Supplement Quality: Quality‑controlled supplements should specify “≥ 95 % anserine, minimal contaminants, GMP‑certified” and provide a certificate of analysis (COA) confirming absence of heavy metals, microbial contamination, and accurate labeling.
Bioavailability: Formulations may use micro-encapsulation or co-delivery with a small amount of carnosine to exploit shared intestinal transporters.