N-ACETYL-L-METHIONINE

CAS: 65-82-7 NUTRIENT SUPPLEMENT

N-Acetyl-L-Methionine is a chemically defined derivative of the essential amino acid methionine used as a nutrient source in human foods and evaluated by food safety authorities in the United States and Europe.

What It Is

N-Acetyl-L-Methionine is a specific derivative of the essential amino acid L-methionine in which an acetyl group is chemically bound to the alpha amino group. It is identified by CAS Number 65-82-7 and is formally recognized in regulatory frameworks for food use as a nutrient supplement. The substance is often referenced in scientific and regulatory literature by alternate names, including acetylmethionine and various systematic synonyms. Its classification as a nutrient supplement reflects its role as a source of methionine, an amino acid that contributes to protein nutrition in human diets. As a nutrient supplement additive in the context of human food, N-Acetyl-L-Methionine is intended to provide an additional source of methionine in processed foods where dietary protein quality is augmented. Methionine itself is essential because the human body cannot synthesize it in sufficient amounts, and it must be obtained through the diet. The acetylated form alters the chemical properties slightly while aiming to deliver the same nutritional benefit as the free L-methionine molecule. Regulatory attention to this additive stems from the requirement to demonstrate that it is safe for intended uses and properly characterized through analytical specifications in food science. In terms of molecular identity, it has a defined molecular formula and structure, and databases such as PubChem catalog the compound with detailed chemical descriptors. Comprehensive chemical databases confirm its identity and synonyms, ensuring that analytical laboratories and regulatory agencies can unambiguously recognize the substance in ingredients lists and specifications. This clear definition supports regulatory and safety evaluation processes around the world.

How It Is Made

N-Acetyl-L-Methionine is produced through a chemical synthesis process in which the naturally occurring amino acid L-methionine undergoes acetylation. In the acetylation reaction, an acetyl group is introduced to the alpha amino group of L-methionine, typically using reagents such as acetic anhydride or similar acetyl-donating chemicals. This reaction yields N-Acetyl-L-Methionine with a high degree of purity when controlled properly. Industrial production designed for food additive use emphasizes adherence to good manufacturing practices and chemical quality standards. The synthesis process begins with a well-defined starting material, purified L-methionine, which is mixed with the acetylating agent under controlled temperature and pH conditions to favor the introduction of the acetyl group at the correct position on the amino acid backbone. The reaction mixture is then subjected to purification procedures, such as crystallization and filtration, which remove unreacted starting material, catalysts, and byproducts. The resulting crystalline or powder form of N-Acetyl-L-Methionine is analyzed for identity, purity, and physical properties that meet food-grade specifications. Food-grade manufacturing specifications generally require a defined purity assay, limits on residual solvents or reagents, and specific optical rotation parameters to confirm the correct stereochemistry. Analytical methods such as high-performance liquid chromatography (HPLC) and optical rotation measurements are commonly used in quality control to verify these characteristics. These production practices align with chemical quality standards like those outlined for amino acid derivatives in food additive monographs and chemical reference compendia. While proprietary details of industrial synthesis can vary among manufacturers, the overarching approach is to achieve a consistent, high-purity product suitable for safe use in food formulations.

Why It Is Used In Food

The primary purpose of using N-Acetyl-L-Methionine in food products is to serve as a source of the essential amino acid methionine, thereby enhancing the protein nutritional quality of certain food formulations. Methionine is one of the essential amino acids required for human growth and maintenance, and it plays roles in protein synthesis, methylation reactions, and other metabolic pathways. Food products that rely on plant proteins or other incomplete protein sources sometimes have lower methionine content relative to human nutritional needs. By adding a methionine source such as N-Acetyl-L-Methionine, food formulators aim to correct amino acid imbalances and improve the biological value of the overall protein content. In regulatory terms, the additive is permitted in specific food categories where its inclusion can meaningfully contribute to overall dietary methionine intake. For example, it may be used in foods where the protein quality is intended to be enhanced to meet nutritional requirements. The rationale for using an acetylated form rather than free L-methionine itself relates to formulation considerations, stability, and, in some cases, sensory characteristics or processing behavior. When consumed, the acetyl group is typically removed enzymatically in the digestive tract, releasing the active amino acid for metabolic use. This enzymatic deacetylation allows the compound to function as a pro-nutrient that ultimately yields the same essential amino acid that the body requires. Food science literature and regulatory evaluations emphasize that the use of such nutrient sources must be substantiated by evidence that they contribute to protein efficiency and meet defined criteria for bioavailability. Regulatory frameworks often include conditions that limit the amount of additive relative to total protein in the finished product to ensure that the intended nutritional benefit is achieved without exceeding safe levels. These conditions guide formulators in determining how best to use the additive in compliant food products.

Adi Example Calculation

To illustrate how intake considerations might be approached for nutrient sources like N-Acetyl-L-Methionine, consider a hypothetical adult with a body weight of 70 kilograms. If a food product formulation includes this compound as part of a fortified protein beverage, the quantity added relative to total protein would be determined by the intended nutritional target for methionine content. For example, if the formulation aims to provide a proportion of methionine equivalent to what would be found in a balanced dietary protein source, the added compound would be calculated to contribute accordingly. In this illustrative scenario, assume that the finished product is designed to deliver an amount of N-Acetyl-L-Methionine that yields a certain fraction of total methionine intake. Because the compound is enzymatically converted to methionine in the body, the calculation focuses on the methionine-equivalent contribution rather than the raw additive mass. The safety assessment would then consider how this additional methionine source fits within the context of overall amino acid intake from the diet and other fortified products. Regulators may require that the use level not exceed a percentage of total protein to prevent disproportionate supplementation. This calculation is illustrative and does not substitute for regulatory conditions or dietary reference values. It demonstrates how formulators and safety assessors might translate compound usage into nutritional impact, aligned with broader dietary needs. Real-world applications depend on product-specific composition and target consumer groups, and adherence to regulatory criteria is essential for safety and compliance.

Safety And Health Research

Safety evaluations of N-Acetyl-L-Methionine center on its role as a source of the essential amino acid methionine and the implications of its metabolic conversion. Safety research examines aspects such as bioavailability, metabolic pathways, and toxicology data relevant to human exposure. Studies and regulatory reviews indicate that the compound is enzymatically deacetylated in the digestive tract, releasing methionine for metabolic use. Comparative studies have shown comparable utilization of methionine released from the acetylated form relative to free L-methionine, suggesting that the body can access the essential amino acid similarly from both sources. These assessments form part of safety evaluations that underpin regulatory decisions. Toxicological data used in safety assessment include information on metabolic fate, acute toxicity, and protein efficiency ratios in experimental models. Regulatory evaluations referenced by authorities such as EFSA noted that exposures to methionine from the use of N-Acetyl-L-Methionine in foods will correspond to exposures from equivalent levels of methionine and are unlikely to raise safety concerns within the evaluated categories. Additionally, requirements for purity and analytical specifications in regulations are designed to limit contaminants and ensure consistent quality that supports safety over a range of intended uses. Where formal toxicological studies are limited, regulators apply risk assessment frameworks that consider biological equivalence to known nutrients, metabolic handling, and available data on enzyme-catalyzed conversion. The absence of broad adverse effect signals in available evaluations supports its safety under specified conditions of use. Nonetheless, ongoing research into amino acid derivatives and their metabolic impacts contributes to the scientific understanding of such compounds. The body of research continues to evolve, and safety assessments may be updated as new evidence emerges.

Regulatory Status Worldwide

In the United States, N-Acetyl-L-Methionine is explicitly recognized in the Code of Federal Regulations. Title 21 CFR Section 172.372 authorizes its use as a food additive that may be safely added to food, with specific conditions, as a source of L-methionine. The regulation outlines identity and specification criteria, including minimum purity and optical rotation parameters, and provides conditions for use relative to total protein content. It also specifies that the additive shall not be added to infant foods or foods containing added nitrites or nitrates. This regulatory provision demonstrates a formal safety determination by the Food and Drug Administration (FDA) for intended uses in nutrient supplementation of certain foods. The presence of this section in the federal regulation reflects safety evaluations and conditions established by FDA based on scientific evidence and risk assessment principles (see sources). In Europe, the European Food Safety Authority (EFSA) has evaluated N-Acetyl-L-Methionine in the context of its use as a source of the essential amino acid in foods for special medical purposes. EFSA’s Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food concluded that its use in this capacity for children over one year of age and adults does not raise safety concerns based on available data. However, the evaluation does not assign an E-number or specific numeric acceptable daily intake (ADI) because the assessment focused on safety in specific marketed categories rather than general population exposure. National authorities in some countries have also recognized its use in dietetic foods for broader age groups, reflecting differing regulatory frameworks across the region. Internationally, authoritative bodies such as JECFA maintain searchable databases of food additive evaluations. At present, a clear monograph with specific ADI values for N-Acetyl-L-Methionine was not identifiable in the public JECFA summaries, and explicit numeric criteria are not established in the widely accessible summaries. The absence of a specific JECFA ADI in the public database suggests that detailed evaluation or specification may be ongoing or limited to compound classes rather than this specific constituent. Nevertheless, the regulatory landscape supports conditional use in defined food applications where its nutritional contribution can be justified.

Taste And Functional Properties

From a sensory standpoint, N-Acetyl-L-Methionine does not impart a distinct flavor that is typically discernible at the low concentrations used for nutritional purposes. Its primary sensory characteristic is neutral or minimally noticeable in the context of complex food matrices. Where additives influence taste, they usually contribute directly to sensory attributes such as sweetness, saltiness, or acidity. In contrast, amino acid derivatives used as nutrient supplements are chosen for their nutritional and functional contributions rather than organoleptic enhancement. As such, N-Acetyl-L-Methionine is formulated to integrate into food systems without adversely affecting flavor profiles. Functionally, the compound behaves as a small, water-soluble molecule that can be easily incorporated into aqueous and semi-solid food systems. It exhibits solubility characteristics typical of amino acid derivatives, dissolving readily in water-based solutions and blending uniformly into formulations where enhanced amino acid profiles are desired. Its stability during food processing is influenced by factors such as temperature, pH, and exposure to reactive food components. The acetylated form can offer some protection against degradation pathways that affect free amino acids, such as participation in Maillard browning reactions under high-heat conditions. Nevertheless, formulators must consider processing parameters and potential interactions with other ingredients to ensure that the additive retains its functional integrity through manufacturing and storage. The functional role of N-Acetyl-L-Methionine thus centers on its nutritional contribution rather than direct flavor modification. It acts as a bioavailable source of methionine following metabolic deacetylation by digestive enzymes. Its inclusion in food products is based on achieving balanced amino acid profiles that support protein quality rather than altering the sensory properties of the final food.

Acceptable Daily Intake Explained

The concept of an acceptable daily intake (ADI) is central to understanding regulatory safety thresholds for food additives. An ADI represents a level of daily exposure, usually expressed in milligrams per kilogram of body weight, that can be consumed over a lifetime without appreciable health risk. ADIs are established by expert bodies based on toxicological data, uncertainty factors, and safety evaluations. They apply to compounds with potential toxicological effects separate from their roles as nutrients or macronutrients. For nutrient supplements such as N-Acetyl-L-Methionine, explicit numeric ADI values are not always assigned because the compound serves as a source of an essential nutrient rather than a non-nutrient additive. When assessments focus on bioavailability and metabolic equivalence to naturally occurring amino acids, regulators may determine that intake within the context of normal dietary patterns does not present safety concerns. In such cases, rather than a specific numeric ADI, conditions of use relative to total protein content and formulation are set. For example, regulatory text may define that the amount of additive used shall not exceed the level that will provide a defined proportion of methionine relative to total protein in the finished food product. This approach acknowledges that essential amino acids are consumed at varying levels in diets, and safety evaluations emphasize that intake should align with nutritional needs and established dietary reference values. Acceptable intake in practical terms is thus guided by meeting needs for methionine without excessive supplementation beyond what is considered nutritionally necessary. Consumers and formulators rely on these regulatory criteria and nutritional guidelines rather than a standalone numeric ADI for this specific compound. Understanding ADIs in this context highlights the distinction between nutrient sources and other food additives that require strict numeric intake limits.

Comparison With Similar Additives

Compared with other amino acid-based nutrient supplements, N-Acetyl-L-Methionine shares functional goals with compounds such as L-lysine or L-threonine when used to enhance protein quality in food products. Each of these amino acids plays an essential role in protein synthesis and metabolic processes, and additives that provide them aim to correct deficiencies in plant-based or other limited protein sources. While free amino acids like L-lysine hydrochloride are commonly used, acetylated forms such as N-Acetyl-L-Methionine are distinct in that they require metabolic conversion before releasing the active amino acid. This difference influences formulation choices and may affect processing behavior. In contrast to flavor-enhancing amino acid derivatives such as monosodium glutamate, which directly impact taste receptors, nutrient supplements focus on nutritional contribution without sensory effects. Another example of a nutrient supplement is L-tryptophan, which, like methionine, is essential and may be added to foods to improve amino acid balance. Both supplements support nutritional completeness but differ chemically and functionally based on their role in metabolism and dietary patterns. The choice between free and acetylated forms often reflects considerations around stability, solubility, and regulatory acceptance in specific food categories. Comparing these additives highlights the broader landscape of food fortification strategies aimed at improving dietary quality through targeted amino acid supplementation. While the mechanisms of delivery differ, the overarching objective is to ensure that finished food products contribute meaningfully to essential nutrient intakes within regulatory frameworks that prioritize safety and nutritional adequacy.

Common Food Applications Narrative

N-Acetyl-L-Methionine is used in a range of food applications where improving the nutritional quality of protein is a priority. Its principal domain lies in specialized food products such as fortified nutrition bars, formulated meal replacements, and protein-enhanced beverages designed to provide balanced amino acid profiles. In these products, the additive supplements naturally occurring proteins that are deficient in methionine to ensure that consumers receive a more complete spectrum of essential amino acids. This is particularly relevant in plant-based products where the inherent methionine content can be lower than that found in animal-derived proteins. By incorporating a defined source of methionine, food developers can raise the protein efficiency ratio of the finished product, aligning it more closely with nutritional targets. In addition to general protein-fortified foods, N-Acetyl-L-Methionine finds application in therapeutic and medical nutrition formulations. Products designed for individuals with specific dietary needs, such as those requiring controlled amino acid intake or enhanced protein utilization, may utilize nutrient supplements to achieve therapeutic or maintenance objectives. In these contexts, precise formulation is guided by clinical and regulatory requirements that dictate amino acid composition relative to dietary protein needs. The additive’s role is to deliver a predictable and measurable increment of methionine, facilitating nutritional adequacy in defined populations. Outside of these targeted categories, protein-fortified snacks and nutritionally tailored foods marketed to athletes or individuals seeking higher protein intake also represent common applications. These products often emphasize balanced essential amino acids to support muscle maintenance and recovery, and methionine supplementation through defined nutrient additives contributes to these claims. While the sensory impact of N-Acetyl-L-Methionine is minimal, its functional contribution to the overall nutritional value of these products is a key consideration for formulators and consumers alike. Across all applications, adherence to regulatory conditions ensures that the additive is used within defined limits and in ways that support consumer expectations for enhanced protein quality.

Safety & Regulations

FDA

  • Approved: True
  • Regulation: 21 CFR 172.372

EFSA

  • Notes: No numeric ADI assigned in EFSA evaluation.
  • Approved: True

JECFA

  • Notes: No specific JECFA entry with numeric ADI found in public database.

Sources

Comments

No comments yet. Be the first to share!