L-Threonine

• Digestive health support
• Immune system function
• Collagen and elastin formation
• Liver function support

• Supports protein synthesis
• Contributes to intestinal mucin production
• Helps maintain gut barrier integrity
• May support neurological function
• Assists in fat metabolism
• Contributes to wound healing

L-Threonine is an essential amino acid with a unique hydroxyl group in its side chain that plays crucial roles in various physiological processes throughout the body. As an essential amino acid, it cannot be synthesized by the human body and must be obtained through diet or supplementation. At the molecular level, threonine serves as a precursor to glycine and serine, two important amino acids involved in neurotransmission, protein synthesis, and one-carbon metabolism. The conversion of threonine to glycine occurs via the threonine dehydrogenase pathway, which is particularly active in the liver and pancreas.

One of threonine’s most significant functions is as a major component of intestinal mucin proteins, which form the protective mucus layer in the gastrointestinal tract. This mucus barrier acts as a physical shield against pathogens, digestive enzymes, and mechanical stress, while also providing a habitat for beneficial gut microbiota. Threonine constitutes up to 30% of the amino acid content of mucins, making it essential for maintaining gut barrier integrity. The amino acid is also incorporated into structural proteins such as collagen and elastin, which are essential for skin, connective tissue, and cardiovascular health.

Threonine residues in these proteins often undergo post-translational modifications, including O-glycosylation, which contributes to their structural and functional properties. In the liver, L-threonine participates in lipotropic functions, helping to prevent fat accumulation through its metabolism to acetyl-CoA and subsequent entry into the TCA cycle. This pathway supports energy production and contributes to the liver’s detoxification processes. Threonine plays a vital role in immune function through multiple mechanisms.

It supports the production of antibodies, which contain relatively high amounts of threonine in their structure. Additionally, threonine is important for the development and function of the thymus gland, a critical organ for T-cell maturation and immune system development. The amino acid is also involved in the synthesis of phospholipids, essential components of cell membranes, particularly in the central nervous system. Through this role, threonine may influence neuronal function and communication.

Metabolically, threonine can be catabolized through several pathways. The major route in humans is via threonine dehydratase, which converts threonine to α-ketobutyrate and eventually to succinyl-CoA, an intermediate in the TCA cycle. Alternatively, threonine can be metabolized via threonine dehydrogenase to 2-amino-3-ketobutyrate, which can then be converted to glycine and acetyl-CoA. A third pathway involves threonine aldolase, which directly converts threonine to glycine and acetaldehyde.

These diverse metabolic fates highlight threonine’s versatility in cellular metabolism and its importance in multiple physiological processes. At the epigenetic level, threonine has been found to influence histone methylation in embryonic stem cells, potentially affecting gene expression patterns and cellular differentiation. This emerging role suggests threonine may have broader implications for development and cellular programming than previously recognized.

500-3000 mg daily for adults, depending on specific health goals

L-Threonine dosage requirements vary based on individual factors including body weight, health status, dietary intake, and specific therapeutic goals. The Recommended Dietary Allowance (RDA) for threonine is approximately 15 mg per kilogram of body weight daily for adults, which translates to roughly 1050 mg for a 70 kg (154 lb) individual. This amount is generally sufficient to prevent deficiency and support basic physiological functions. However, therapeutic applications often require higher doses.

For general health maintenance and to supplement a typical diet, 500-1000 mg daily is commonly recommended. This dosage helps ensure adequate threonine levels for protein synthesis, immune function, and gut health, particularly for individuals with limited intake of threonine-rich foods or increased requirements due to physical activity or stress. For specific digestive disorders, particularly those involving compromised intestinal barrier function or reduced mucin production, higher doses of 1000-3000 mg daily may be beneficial. This range supports the synthesis of intestinal mucins, which form the protective mucus layer in the gut.

The upper end of this range is typically reserved for more severe conditions and should be approached under healthcare supervision. Immune support applications generally utilize 1000-2000 mg daily, which may enhance antibody production and support thymus function. This dosage range is often employed during periods of increased immune challenge or for individuals with compromised immune function. For liver support and to assist with fat metabolism, 1000-2000 mg daily is commonly recommended.

This dosage may help prevent fat accumulation in the liver and support detoxification processes, particularly in individuals with metabolic challenges or those at risk for fatty liver disease. Older adults may benefit from slightly higher intake due to potential decreases in protein digestion and amino acid absorption that often accompany aging. In contrast, supplementation in children and adolescents is not typically recommended unless specifically indicated for medical reasons, as their threonine requirements are generally met through a balanced diet.

L-Threonine is best absorbed when taken on an empty stomach, at least 30 minutes before meals or 2 hours after eating. This minimizes competition with other amino acids for intestinal absorption. For digestive health applications, taking threonine 30-60 minutes before meals may help ensure adequate mucin production during digestion. When used for immune or liver support, consistent daily supplementation is more important than specific timing.

For sleep support (a secondary benefit noted by some users), taking threonine approximately 30-60 minutes before bedtime may be beneficial, as it can be converted to glycine, which has mild sleep-promoting effects.

For general health maintenance, continuous use is appropriate without specific cycling protocols. For therapeutic applications, some practitioners recommend 8-12 weeks of consistent supplementation followed by a 2-4 week break to prevent potential downregulation of endogenous pathways, though clinical evidence for this approach is limited. For seasonal immune support, threonine supplementation may be focused during fall and winter months when immune challenges are typically greater.

Approximately 75-85% from dietary sources and supplements in free-form

L-Threonine demonstrates good bioavailability compared to many other amino acids, with absorption rates typically ranging from 75-85% when consumed in free form. Absorption occurs primarily in the small intestine through sodium-dependent active transport systems, particularly the B0 system (neutral amino acid transporter) and the ASC system (alanine-serine-cysteine preferring transporter). These transport systems are relatively efficient but can become saturated at high doses, potentially limiting absorption of very large single doses. Several factors influence threonine absorption and utilization.

When consumed as part of intact proteins in food, threonine must first be liberated through digestion, which can reduce overall bioavailability compared to free-form supplements. The presence of other amino acids, particularly those that use the same transport systems (such as alanine, serine, and other neutral amino acids), can create competition for absorption. This competition is most significant when threonine is consumed as part of a high-protein meal or with other amino acid supplements. Digestive health also plays a crucial role in threonine bioavailability.

Conditions that affect the integrity of the intestinal mucosa or reduce digestive enzyme production can impair threonine absorption. Conversely, threonine itself supports intestinal health through its role in mucin production, creating a potential positive feedback loop where adequate threonine status helps maintain the very systems responsible for its absorption. Once absorbed, threonine enters the portal circulation and is transported to the liver, where a significant portion (approximately 20-30%) undergoes first-pass metabolism. The remaining threonine enters the systemic circulation and is distributed to tissues throughout the body.

Threonine can cross the blood-brain barrier, though it competes with other neutral amino acids for the limited transport capacity. The plasma half-life of free threonine is relatively short (approximately 2-3 hours), suggesting that divided doses throughout the day may maintain more consistent blood levels for therapeutic purposes.

General Health: For general health support, L-threonine can be taken once daily, preferably on an empty stomach to maximize absorption. Morning administration is common, though no specific time of day has been shown to be clearly superior.

Digestive Health: For digestive health applications, taking threonine 30-60 minutes before meals may help ensure adequate mucin production during digestion. For individuals with three regular meals, a schedule of 30 minutes before breakfast and dinner may be practical and effective.

Immune Support: For immune support, consistent daily supplementation is more important than specific timing. However, taking threonine in the morning may align with the natural circadian rhythm of certain immune functions.

Liver Support: For liver support, taking threonine in divided doses (morning and evening) may provide more consistent support for metabolic functions throughout the day.

Pre Workout: Some athletes take threonine 30-60 minutes before exercise to support protein synthesis during and after physical activity, though evidence for timing-specific benefits is limited.

Post Workout: Taking threonine within 30-60 minutes post-exercise may support recovery and protein synthesis, particularly when combined with other amino acids and carbohydrates.

L-Threonine is generally considered safe for most healthy adults when used at recommended dosages. As an essential amino acid naturally present in dietary proteins, it has a favorable safety profile compared to many other supplements. Most individuals can tolerate threonine supplementation without significant adverse effects, particularly at doses of 500-3000 mg daily. The body has regulatory mechanisms to manage threonine metabolism, including the ability to catabolize excess threonine through several pathways or excrete it.

However, as with any bioactive compound, there are some safety considerations to be aware of. High doses (above 5000 mg daily) have not been well-studied for long-term safety and may potentially disrupt the balance of other amino acids or place additional burden on liver and kidney function. Individuals with pre-existing liver or kidney disease should exercise caution with threonine supplementation, as these organs are involved in amino acid metabolism and clearance. There is also limited research on threonine supplementation during pregnancy and lactation, so a cautious approach is warranted for these populations.

Rare genetic disorders of threonine metabolism, such as threoninemia, are absolute contraindications for threonine supplementation, as affected individuals cannot properly metabolize this amino acid. While serious adverse events from threonine supplementation are rare in the scientific literature, the relatively limited number of controlled clinical trials means that uncommon side effects may not yet be well-documented. Most reported side effects are mild and transient, often resolving with continued use or reduction in dosage.

Established Limit: No officially established upper limit by regulatory authorities

Research Based Guidance: Doses above 5000 mg daily have not been well-studied for safety

Theoretical Concerns: Extremely high doses might potentially disrupt amino acid balance, place burden on liver/kidney function, or interfere with the metabolism of other amino acids

Practical Recommendation: For most individuals, staying within the 500-3000 mg daily range is prudent until more safety data becomes available

Children: Not recommended for supplementation unless specifically prescribed by a healthcare provider for particular medical conditions

Elderly: Generally safe, but may be more susceptible to side effects due to potential changes in liver and kidney function; starting with lower doses is advisable

Liver Impairment: Use with caution and at reduced doses, if at all; consult healthcare provider

Kidney Impairment: Use with caution and at reduced doses, if at all; consult healthcare provider

Genetic Considerations: Individuals with known disorders of threonine metabolism should avoid supplementation

Limited data exists on the long-term safety of threonine supplementation beyond 1-2 years. Based on its presence in the normal diet and status as an essential amino acid, significant long-term adverse effects are not anticipated at recommended doses, but formal studies are lacking. Some animal studies suggest that very high threonine intake over extended periods might influence liver and kidney function, but these findings have not been confirmed in humans at typical supplemental doses.

Classification: Generally Recognized as Safe (GRAS) as a nutritional supplement

Detailed Information: In the United States, L-threonine is classified as Generally Recognized as Safe (GRAS) by the Food and Drug Administration (FDA) when used as a nutritional supplement. This classification allows it to be added to dietary supplements without premarket approval, based on its history of safe use and scientific consensus regarding its safety. The FDA does not specifically regulate the dosage of L-threonine in supplements, though manufacturers are required to follow Good Manufacturing Practices (GMPs) and ensure their products are safe, properly labeled, and contain the ingredients listed on the label. L-threonine is also permitted as a food additive for special dietary foods and medical foods. It is not approved as a drug for the treatment, prevention, or cure of any disease, and supplement manufacturers must avoid making specific disease claims about products containing threonine.

Labeling Requirements: Products containing L-threonine must comply with standard dietary supplement labeling requirements, including listing the amount per serving, percent daily value (though no official daily value has been established for threonine), and the standard supplement facts panel. Any structure/function claims must be accompanied by the FDA disclaimer stating that the product has not been evaluated by the FDA and is not intended to diagnose, treat, cure, or prevent any disease.

Recent Regulatory Changes: No significant recent changes in FDA regulatory status for L-threonine. It continues to be regulated under the Dietary Supplement Health and Education Act (DSHEA) of 1994 framework.

Tariff Classifications: 2922.50.1125 – Amino-acids, other than those containing more than one kind of oxygen function; other: Amino-acids and their esters, other than those containing more than one kind of oxygen function; other: Amino-acids: Other: L-Threonine, Vary by country and trade agreements; generally low to moderate for pharmaceutical and food grade amino acids

Country Specific Requirements: FDA Prior Notice required for food and supplement imports containing L-threonine. May be subject to FDA import inspection., Compliance with EU food and supplement regulations required for import. May require specific documentation regarding source, purity, and non-GMO status depending on intended use., Stringent import requirements for supplements and food additives, including registration with appropriate Chinese authorities and Chinese-language labeling.

Documentation: Typical required documents include Certificate of Analysis, Certificate of Origin, Safety Data Sheet, and documentation of GMP compliance for supplement or pharmaceutical applications.

2023-11-15

Medium

L-Threonine supplements occupy a middle ground in the amino acid supplement market in terms of cost. They are generally more expensive than common amino acids like glycine but less costly than specialized or rare amino acids such as L-carnosine or L-ergothioneine. The production methods for L-threonine, primarily bacterial fermentation, have become more efficient over time, helping to maintain relatively stable pricing despite increasing demand. The large-scale production for animal feed applications has also helped drive down costs for human-grade threonine.

The price of L-threonine supplements can vary considerably based on several factors, including purity level (pharmaceutical grade commands premium prices), brand reputation, additional ingredients in the formulation, and packaging format. Specialized delivery systems, such as sustained-release technologies, typically command price premiums of 30-50% over standard forms. When evaluating cost-efficiency, it’s important to consider not just the price per gram of L-threonine but also bioavailability and targeted health outcomes. For example, lower-cost forms may contain D-threonine or mixed isomers with reduced biological activity, making them less cost-effective despite their lower price point.

Similarly, formulations that combine L-threonine with synergistic nutrients like vitamin B6 may provide better results for specific purposes, potentially offering better value despite higher initial cost.

Average Retail Cost: $0.30-$0.80 per day for 1000mg

Price Range By Form: $0.15-$0.40 per gram (lowest cost option), $0.25-$0.60 per gram, $0.30-$0.65 per gram, $0.40-$0.90 per gram (sustained-release, etc.)

Price Range By Quality: $0.20-$0.45 per gram, $0.40-$0.80 per gram, $0.10-$0.20 per gram (not recommended for human consumption)

Price Trends: Prices have remained relatively stable over the past 5 years, with slight decreases due to improved production efficiencies offset by increased demand for amino acid supplements generally. Seasonal variations are minimal, though bulk purchasing during major sales events can offer savings of 20-30%.

General Assessment: Moderate cost for potential benefits, especially for digestive and immune support. Food sources may be more cost-effective for general maintenance, but supplements offer precise dosing and convenience for therapeutic applications. For specific conditions involving intestinal health or immune function, the cost-to-benefit ratio may be more favorable than for general preventative use.

Comparison To Alternatives: Complete protein supplements (providing threonine along with other amino acids) typically cost $0.05-$0.15 per gram of protein, making them a more economical source of threonine for general purposes. However, they provide lower concentrations of threonine and may not be suitable for targeted therapeutic applications., Dietary sources such as meat, eggs, and dairy (approximately $0.05-$0.20 per gram of protein, containing about 3-4.5% threonine) are generally more economical but provide variable and lower concentrations of threonine along with many other nutrients. For therapeutic doses, supplements may be more practical despite higher cost per gram., Compared to specialized digestive health supplements such as glutamine ($0.15-$0.40/g), probiotics ($0.30-$1.00 per day), or specialized gut health formulations ($0.50-$2.00 per day), L-threonine is moderately priced and may offer complementary benefits when used as part of a comprehensive approach.

Cost Effectiveness By Application:

Health Insurance: L-threonine supplements are generally not covered by standard health insurance plans in most countries, as they are classified as dietary supplements rather than prescription medications.

Fsa Hsa Eligibility: In the United States, L-threonine supplements may be eligible for purchase using Flexible Spending Account (FSA) or Health Savings Account (HSA) funds if prescribed by a healthcare provider for a specific medical condition. A Letter of Medical Necessity is typically required.

Exceptions: Some specialized medical nutrition programs may include coverage for specific amino acid supplements including threonine, particularly in cases of metabolic disorders or specific digestive conditions, but this is highly variable by provider and plan.

Powder Form: 2-3 years when properly stored in original sealed container

Capsule Form: 2-3 years when properly stored in original sealed container

Tablet Form: 2-3 years when properly stored in original sealed container

Liquid Form: 1-2 years when properly stored in original sealed container

After Opening: Best used within 6-12 months after opening original container

L-Threonine is relatively stable compared to many other amino acids, particularly those with more reactive side chains. The hydroxyl group in threonine’s side chain does make it somewhat more reactive than amino acids with aliphatic side chains, but less reactive than those with sulfur-containing or aromatic groups. In its pure crystalline form, L-threonine is quite stable when protected from extreme environmental factors. The primary degradation pathways include oxidation, racemization (conversion from the biologically active L-form to the inactive D-form), Maillard reactions (when in the presence of reducing sugars), and hydrolysis under extreme pH conditions.

Degradation typically accelerates when threonine is in solution rather than in solid form, with the rate increasing at higher temperatures and extreme pH values. The stability of threonine in supplement formulations is influenced by the presence of other ingredients, the pH of the formulation, and the specific manufacturing processes used. Tablets and capsules generally offer better stability than liquid formulations due to the reduced water activity and limited exposure to oxygen. Stability testing by manufacturers typically involves accelerated aging studies under controlled temperature and humidity conditions to predict shelf life under normal storage conditions.

When properly stored, L-threonine typically maintains at least 95% of its original potency for 2-3 years in solid forms.

Temperature: Store at room temperature (15-25°C or 59-77°F). Avoid temperature extremes; prolonged exposure to temperatures above 30°C (86°F) may accelerate degradation. Refrigeration is not necessary but may extend shelf life in very warm climates.

Humidity: Store in a dry place with relative humidity below 60%. L-threonine can absorb moisture from the air, which may lead to degradation or clumping. Areas with high humidity, such as bathrooms, should be avoided for storage.

Light Exposure: Protect from direct sunlight and strong artificial light, which can promote oxidation reactions. Amber or opaque containers provide better protection than clear containers. If the original container is clear, storing it inside a cabinet or drawer is advisable.

Container Type: Keep in airtight containers with minimal headspace to reduce exposure to oxygen. Original containers with desiccant packets are ideal for maintaining stability. If transferring to another container, choose one that can be tightly sealed and consider adding a desiccant packet.

Special Considerations: After opening, ensure the container is tightly resealed after each use. Consider transferring to smaller containers as the product is used to minimize headspace and repeated exposure to air. Avoid using wet utensils to remove powder from containers, as this can introduce moisture and promote degradation.

Compatible Ingredients: Most vitamins and minerals at appropriate concentrations, Other amino acids (though may compete for absorption), Most herbal extracts, Common excipients used in supplement manufacturing (microcrystalline cellulose, silicon dioxide, etc.), Mild organic acids (citric acid, malic acid) at moderate concentrations

Potentially Incompatible Ingredients: Strong oxidizing agents or ingredients that generate peroxides, Reducing sugars (may lead to Maillard reactions over time, particularly in liquid formulations), High concentrations of certain transition metal ions without chelating agents, Highly acidic or alkaline ingredients without appropriate buffering, Certain enzymes that may catalyze threonine degradation

Formulation Considerations: In multi-ingredient formulations, the stability of threonine may be enhanced by the inclusion of antioxidants (such as vitamin E or rosemary extract), chelating agents (such as EDTA in appropriate applications), and proper pH adjustment. Separation of potentially reactive ingredients into different layers or compartments in tablets or capsules may also improve stability. For liquid formulations, using a nitrogen flush during packaging can reduce oxidation potential.

Accelerated stability testing (elevated temperature and humidity conditions to predict long-term stability), Real-time stability testing (storage under recommended conditions with periodic testing), HPLC analysis for purity and detection of degradation products, Mass spectrometry for identification of specific degradation pathways, Microbial testing to ensure product remains free from significant contamination, Dissolution testing for tablets and capsules to ensure they maintain proper disintegration properties over time, Moisture content analysis to monitor potential water absorption, pH monitoring for liquid formulations to detect potential changes over time

Synthesis Methods

Natural Sources

Quality Considerations

Sustainability Considerations

Market Considerations

Threonine has a unique place in the history of nutritional science as the last of the 20 standard amino acids to be discovered and the final essential amino acid to be identified. Its isolation and characterization represent a significant milestone in our understanding of human nutrition and protein biochemistry. The amino acid was first isolated in 1935 by American biochemist William Cumming Rose and his colleagues at the University of Illinois. Rose was conducting systematic studies to identify all the amino acids essential for rat growth, and threonine completed this fundamental work.

The name ‘threonine’ was derived from threonose, a sugar compound it structurally resembles due to its hydroxyl group. This discovery was particularly significant because it completed the set of amino acids that cannot be synthesized by the human body and must be obtained through diet. In 1936, shortly after its discovery, Rose demonstrated that threonine was essential for human nutrition as well, through careful dietary studies. This work helped establish the concept of essential amino acids and their importance in human health, fundamentally changing our approach to protein nutrition.

Unlike some other amino acids that had been known for decades or even centuries before their nutritional significance was understood, threonine’s discovery coincided with the recognition of its essential nature. While threonine was not prominently featured in traditional medicine systems (as its isolated form was unknown before the 20th century), foods rich in this amino acid have long been valued for their nutritional properties. Traditional diets worldwide typically included protein-rich foods that provided adequate threonine, such as meat, fish, eggs, and dairy products. In agricultural contexts, threonine gained importance in the mid-20th century as research established its essentiality for livestock growth and development.

By the 1980s, feed-grade L-threonine was being commercially produced for animal nutrition, particularly for swine and poultry, where it is often a limiting amino acid in plant-based feeds. This application continues to represent the largest market for threonine production today. The development of efficient fermentation processes for threonine production in the 1980s and 1990s, using genetically modified bacteria, significantly reduced production costs and increased availability for both animal and human applications. These technological advances made threonine supplementation economically viable for a wider range of uses.

In human nutrition, interest in threonine supplementation began to expand in the 1990s and early 2000s as research revealed its specific roles beyond basic protein synthesis. Studies highlighting threonine’s importance in intestinal mucin production, immune function, and liver metabolism opened new potential therapeutic applications. The use of threonine in clinical nutrition, particularly for patients with digestive disorders or compromised intestinal function, has gradually increased as evidence for its specific benefits has accumulated. In recent decades, threonine has also gained attention in sports nutrition and general health supplementation, though it remains less widely used as an individual supplement compared to some other amino acids like leucine or glutamine.

Modern research continues to explore threonine’s roles in gut health, immune function, and metabolic regulation, with emerging evidence suggesting potential applications in conditions ranging from irritable bowel syndrome to fatty liver disease. Throughout its relatively short history as a known nutrient, threonine has transitioned from a newly discovered essential amino acid to a recognized component in nutritional and supplementation strategies for both animal and human health. Its story illustrates how advances in biochemistry and nutrition science in the 20th century transformed our understanding of protein requirements and opened new possibilities for targeted nutritional interventions.

The scientific evidence for L-threonine supplementation is moderate, with strong mechanistic data supporting its roles in protein synthesis, intestinal mucin production, and immune function. Human clinical trials specifically evaluating threonine supplementation are limited in number and scope, with most research focusing on its metabolic roles rather than therapeutic applications. The strongest evidence exists for threonine’s importance in intestinal health, particularly its role in mucin production and gut barrier function, with moderate evidence for benefits in immune support and liver health. Research on other potential benefits, such as neurological function and wound healing, remains preliminary.

While threonine’s biochemical functions are well-established in laboratory and animal studies, more rigorous human clinical trials are needed to definitively establish the efficacy, optimal dosing, and specific indications for L-threonine supplementation.

Limited long-term human clinical trials specifically evaluating threonine supplementation for various health conditions, Insufficient dose-response studies to determine optimal therapeutic dosages for specific conditions, Limited research on potential benefits for neurological conditions, despite threonine’s role as a precursor to glycine and serine, Inadequate studies comparing different forms of threonine supplementation for bioavailability and efficacy, Few studies examining genetic or individual factors that might influence response to threonine supplementation, Limited research on threonine’s potential role in epigenetic regulation, particularly histone methylation in humans, Insufficient studies in diverse populations, with most research conducted in young, healthy adults or specific disease models