IngredientsL-Threonine is the (2S,3R)-2-amino-3-hydroxybutanoic acid stereoisomer, the biologically active form of the amino acid threonine. It is catalogued under CAS Registry Number 72-19-5, with the molecular formula C₄H₉NO₃ and molecular weight 119.1192. Its systematic IUPAC name is (2S,3R)-2-amino-3-hydroxybutanoic acid, and it is also known by the names L-α-amino-β-hydroxybutyric acid and threonin. Its three-letter code is Thr and its one-letter code is T; its codons are ACU and ACA (and also ACC and ACG), and its systematic name is 2-amino-3-hydroxybutanoic acid.
Threonine is one of only two proteinogenic amino acids with two stereogenic centers, the other being isoleucine. Threonine can exist in four possible stereoisomers with the following configurations: (2S,3R), (2R,3S), (2S,3S), and (2R,3R). The name L-threonine is used for one single enantiomer, (2S,3R)-2-amino-3-hydroxybutanoic acid — this is the only form used in mammalian proteins. The second diastereomer, (2S,3S), which is rarely present in nature, is called L-allothreonine.
L-Threonine contains an α-amino group (in the protonated −NH₃⁺ form when dissolved in water), a carboxyl group (in the deprotonated −COO⁻ form when dissolved in water), and a side chain containing a hydroxyl group, making it a polar, uncharged amino acid. Serine and threonine are polar, hydrophilic amino acids characterized by hydroxyl groups in their side chains, enabling them to establish hydrogen bonds and engage in phosphorylation. The primary distinction between them is that serine possesses a smaller hydroxymethyl group (–CH₂OH), whereas threonine contains a larger hydroxyethyl group (–CH(OH)CH₃) with an extra methyl group (–CH₃).
As an essential amino acid, threonine is not synthesized in humans and needs to be present in proteins in the diet. Threonine is an α-amino acid that is common in many proteins and, together with serine and tyrosine, is one of three proteinogenic amino acids bearing an alcohol group.
L-Threonine is the last common amino acid to be discovered. Although biochemist William C. Rose and colleagues at the University of Illinois (Urbana–Champaign) are usually credited with discovering it in 1936, biochemist Samuel B. Schryver and botanist H. W. Buston at Imperial College London reported isolating it from oat protein in 1926. It was named threonine because it has a structure similar to threonic acid, a four-carbon monosaccharide with molecular formula C₄H₈O₅.
Rose and his colleagues used laborious techniques available before the development of chromatography to purify the new amino acid from a mixture of 19 known amino acids. It was crystallized, and the structure was determined to be α-amino-β-hydroxy-n-butyric acid, later named threonine. With the addition of threonine to the other 19 amino acids, rats were, for the first time, successfully reared on a diet in which pure amino acids were the sole source of nitrogen. Over the next 20 years, Rose extended his studies to quantify the dietary requirements for individual amino acids. This quantitative work distinguished the amino acids that are absolutely essential from those that are necessary only for optimal growth. For rats, the omission of histidine, isoleucine, leucine, threonine, lysine, methionine, phenylalanine, tryptophan, or valine resulted in eventual death.
Foods high in threonine include milk, cottage cheese, poultry, fish, meat, lentils, sesame seeds, eggs, beans, corn, and various grains. Natural food sources include marine products (salmon, tuna, mackerel), meat products (beef, pork, chicken), dairy products (cheese, yogurt), legumes (peas, peanuts, almonds), and grain products (soybean, tofu, miso), as well as corn, eggs, and milk.
In plants and microorganisms, threonine is synthesized from aspartic acid via α-aspartyl-semialdehyde and homoserine. Because of the existence of stereoisomers, production of only the L-isomer is difficult by chemical synthesis, and it is primarily produced industrially by the fermentation method.
Threonine can be found in nutraceuticals, dietary supplements, and nutritional preparations in the form of capsules, gummies, syrups, and other multivitamins and mineral compounds. As a free-form amino acid supplement, it is commercially available as a crystalline powder and in capsule form. Most commercially supplied threonine today is synthesized rather than being obtained from natural proteins.
L-Threonine has no documented history of use as an isolated compound in pre-modern herbal or traditional medical systems, for the straightforward reason that its very existence was unknown until the twentieth century. It is the last common amino acid to be discovered, with its isolation credited to William C. Rose's laboratory work in the 1930s. Threonine-containing proteins from animal and plant foods have, of course, been consumed throughout human history, but the constituent amino acid was not identified or used intentionally in any documented traditional pharmacopeia.
It was the last of the protein amino acids to be discovered, in 1935, in studies of nitrogen balance on subjects fed mixtures of the then-known amino acids in place of proteins. The earliest clinical applications emerged from mid-twentieth-century research into amino acid deficiency diseases and protein metabolism, rather than from ethnobotanical or folk medicine traditions. Interest in L-threonine as a targeted therapeutic supplement developed from the 1980s onward, principally from neurological research into spasticity and from nutritional science investigations into gut mucosal integrity. These are discussed in detail in the scientific evidence sections below.
As an essential amino acid, threonine is involved in the metabolism of fats, the creation of proteins, the proliferation and differentiation of embryonic stem cells, and the health and function of the intestines. The threonine residue is susceptible to numerous posttranslational modifications.
The hydroxyl side chain of threonine can undergo O-linked glycosylation (addition of saccharides). Additionally, threonine residues undergo phosphorylation (addition of phosphate) through the action of a threonine kinase. In its phosphorylated form, it can be referred to as phosphothreonine.
Phosphorylation is the most common type of posttranslational modification, and involves adding a phosphate group to amino acids such as serine, threonine, and tyrosine. By adding a phosphate group, the electrostatic interactions in the protein are changed, which can disrupt the activity of the enzyme or protein. O-linked glycosylation takes place in the Golgi apparatus and involves the addition of a glycosyl group to the hydroxyl group on serine and threonine amino acid residues. O-linked glycosylation has been found to be important in the production of proteins released in mucus secretions and proteoglycans, which are a component of the extracellular matrix.
Threonine has the ability to cross over into the catabolic pathway, where it can be converted into a wide range of essential metabolites including glycine, acetyl-CoA, and pyruvate that are essential to the metabolism of the host. Most mammals need threonine as a precursor for glycine synthesis, and studies have demonstrated that supplementing with threonine raises the levels of glycine neurotransmitters in rats' brains and plasma glycine in pigs. As threonine is used by the body to produce other amino acids, including serine and glycine, a sufficient absorption of threonine is highly important to also generate these two amino acids; serine and glycine are important for the production of collagen in the organism.
Threonine plays a critical role in the maintenance of intestinal mucosal integrity and barrier function, which can be indicated by intestinal morphology, mucus production (number of goblet cells), transepithelial permeability, brush border enzyme activity, and growth performance. Dietary threonine restriction may decrease the production of digestive enzymes and increase mucosal paracellular permeability. A large proportion of dietary threonine is utilized for intestinal-mucosal protein synthesis, especially for mucin synthesis, and there is no oxidation of threonine by enterocytes.
The most abundant mucin synthesized in goblet cells of the small and large intestines is MUC2. MUC2 is a secreted mucin that is particularly rich in threonine and is involved in forming the extraepithelial mucus matrix. Because mucin proteins cannot be digested and reused, intestinal mucin secretion is a net loss of threonine from the body. Luminal threonine availability can influence synthesis of intestinal mucins and other proteins.
Evidence indicates that excess threonine is converted to carbohydrate, liver lipids, and carbon dioxide. Threonine, together with methionine and aspartic acid, participates in lipotropic activity — the regulation of fat transport and metabolism in the liver. Threonine deficiency has been shown in animal models to alter energy processing in the liver, including fat metabolism.
Threonine is changed in the body to a chemical called glycine. Glycine has effects in the brain that might reduce unwanted muscle contractions called spasticity. Preclinical data indicate that the administration of L-threonine increases glycine levels in rat spinal cord. Glycine is an inhibitory neurotransmitter in the spinal cord, and it is via this precursor relationship that threonine has been studied in neurological conditions. Glycine and GABA are the two main inhibitory neurotransmitters in the CNS that activate different ionotropic receptors permeable to chloride ions.
Threonine is an important constituent in many body proteins and is necessary for the formation of tooth enamel protein, collagen, and elastin, which are both needed for healthy skin and wound healing. Many of threonine's functions are due to its presence as a residue of specific proteins, including collagen, elastin, and enamel.
Research published in Cold Spring Harbor Perspectives in Biology states that serine/threonine kinases control the epigenetic, transcriptional, and metabolic programs that determine T-cell function. At a basic level, serine and threonine kinases work as a series of on/off switches that trigger antigen and cytokine receptors that make up the immune system.
Threonine levels in human and mouse embryonic stem cells can control the proliferation and G1/S phase transition of the cell cycle.
Mechanism and animal/preclinical evidence: The relationship between threonine and gut mucosal integrity has been studied primarily in animal models. In a 14-day rat study, male Sprague-Dawley rats were fed isonitrogenous diets containing 30%, 60%, 100% (control), or 150% of the theoretical threonine requirement for growth. The mucin and mucosal protein fractional synthesis rates did not differ from controls in the 60% group. By contrast, the mucin fractional synthesis rate was significantly lower in the duodenum, ileum, and colon of the 30% group compared with controls, whereas the corresponding mucosal protein fractional synthesis rate did not differ. Because mucin mRNA levels did not differ between these two groups, mucin production was likely impaired at the translational level. These results clearly indicate that restriction of dietary threonine significantly and specifically impairs intestinal mucin synthesis.
A continuously perfused gut loop model and intraluminal flooding dose technique were used in six young pigs to study the acute effects of varying luminal availability of threonine on intestinal protein and mucin syntheses. A complete amino acid mixture containing 0, 21, or 56 mg threonine per gram of total amino acids was continuously perfused in isolated loops for 120 minutes. Fractional rates of total mucosal protein synthesis were higher in loops perfused with 56 mg/g compared with 0 mg/g and 21 mg/g. For mucin, fractional rates of synthesis differed significantly across all three concentrations. De novo synthesis of mucosal and mucin proteins is acutely sensitive to luminal threonine concentration, demonstrating the importance of dietary amino acid supply to gut protein metabolism.
The high requirement of the gut for threonine has often been ascribed to the synthesis of mucins, secreted threonine-rich glycoproteins protecting the intestinal epithelium from injury. This requirement could be even greater during intestinal inflammation, when mucin synthesis is enhanced. In a minipig model of experimental ileitis, ileal mucin fractional synthesis rate was greater in the inflamed group (114 ± 15%/d) than in the control group (61 ± 8%/d). PDV uptake of arterial threonine increased substantially in the inflamed group. Ileitis increased intestinal mucin synthesis and PDV utilization of threonine from arterial but not luminal supply, leading to mobilization of endogenous proteins to meet the increased threonine demand associated with acute intestinal inflammation.
Applicability to humans: Under pathological conditions such as ileitis and sepsis, threonine requirement may be increased to maintain intestinal morphology and physiology. Knowledge about the role of threonine in mucin synthesis is critical for improving gut health under physiological and pathological conditions in animals and humans. The direct human clinical evidence for threonine supplementation improving gut barrier function remains limited; most mechanistic data are derived from animal models.
Evidence strength: Mechanistic evidence in animals is robust; direct human interventional data are sparse.
Rationale: Preclinical data indicate that the administration of L-threonine increases glycine levels in rat spinal cord. Based on this observation, several clinical trials were conducted beginning in the 1980s to determine whether oral L-threonine could reduce spasticity in humans by augmenting spinal glycinergic inhibitory neurotransmission.
Pilot uncontrolled study (Barbeau et al., 1982): Threonine supplementation at 500 mg/day was given to 6 patients with genetic spasticity syndromes for a period of 12 months, followed by a 4-month observation period without medication. All 6 patients showed partial improvement of spasticity, intensity of knee jerks, and muscle spasms without changes in true pyramidal tract signs. The improvement in motor performance, objectively measured, averaged 29% (19% in upper limbs and 42% in lower limbs). The range of overall improvement was 19–35% (7–30% for upper limbs; 25–67% for lower limbs). No toxic clinical or biochemical side effects were encountered. Threonine, as a precursor of glycine, produced the same effect on spasticity as that previously observed with glycine.
Double-blind crossover trial in familial spastic paraparesis (Growdon et al., 1991): In order to investigate glycinergic mechanisms in spasticity, 4.5 and 6.0 g/day of L-threonine were given to 18 patients with familial spastic paraparesis (FSP) according to a double-blind, crossover protocol. The response to treatment at the end of each 2-week period was based upon three measures: the physician's global impressions; the patients' global impressions; and semiquantitative ratings of strength, muscle tone, DTRs, walking, hopping, and running. The data indicate that L-threonine significantly suppressed the signs of spasticity, even though the benefits were not clinically valuable.
Double-blind crossover trial in multiple sclerosis (Hauser et al., 1992): To determine whether threonine, a potential precursor for glycine biosynthesis in the spinal cord, has an effect on spasticity in multiple sclerosis, 26 ambulatory patients were entered into a randomized crossover trial. Threonine administered at a total daily dose of 7.5 g reduced signs of spasticity on clinical examination, although no symptomatic improvement could be detected by the examining physician or the patient. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used for the treatment of multiple sclerosis, no side effects or toxic effects of threonine were identified.
Double-blind study in spinal spasticity (Lee and Patterson, 1993): A double-blind, placebo-controlled, crossover study of oral L-threonine at 6 g/day was conducted in patients with spinal spasticity. Muscle tone from selected leg muscles, measured by the Ashworth Scale, was the principal measure of spasticity and was evaluated before and at the end of each treatment period. A 10% reduction in Ashworth score was regarded as a positive response. The trial concluded in favour of L-threonine after 33 patients, with minimal side effects. L-threonine has a modest but definite antispastic effect, and its possible role in modifying spinal glycinergic transmission was discussed.
Evidence strength: Multiple small clinical trials (including randomized, double-blind, placebo-controlled crossover designs) provide consistent evidence of a statistically significant but modest reduction in objective spasticity measures. The clinical meaningfulness of this effect has been described as limited in several trials. In previous open studies, L-threonine had been given to patients with spasticity in doses ranging from 1.5 to 3 g/day. The lower dosage was ineffective but 3 g/day produced a modest effect, leading to the decision to test the antispastic effect using higher doses. Overall, the evidence is graded as modest in strength: statistically significant effects in multiple small controlled trials, but limited functional/symptomatic benefit observed.
A pilot study showed that L-threonine, an essential amino acid, may be effective in the symptomatic treatment of ALS. Thirty patients suffering from amyotrophic lateral sclerosis were included in an open therapeutic trial. They were randomized to receive either L-threonine (a precursor of the inhibitory amino acid glycine), vitamin B, or carnitine. WebMD notes that people use threonine for ALS and multiple sclerosis, but states there is no good scientific evidence to support these uses. The rationale lies in deficient glycinergic innervation documented in ALS animal models: glycine transporter-2 bouton density on lateral motoneurons was decreased significantly in G93A-SOD1 mice compared with controls, suggesting that augmenting glycine supply via threonine supplementation might be theoretically beneficial. However, large controlled clinical trial evidence is lacking and no established therapeutic role has been confirmed.
Evidence strength: Very weak — limited to small pilot studies and mechanistic rationale; the Cochrane Database has reviewed amino acids for ALS/motor neuron disease without endorsing their clinical use.
Animal research has linked dietary threonine deficiency to altered hepatic lipid metabolism. An animal study found that threonine-deficient diets increase mitochondrial uncoupling in the liver, meaning that diets lacking quality protein foods that provide essential amino acids can lead to cell malfunction and the buildup of fats in the liver. Threonine is involved in fat metabolism and can help prevent fat accumulation in organs like the liver. Its role in lipid metabolism makes threonine potentially helpful for fighting metabolic diseases, including cardiovascular disease. These findings are predominantly from animal models; direct human clinical trial evidence for threonine supplementation reversing or preventing fatty liver is not established.
Evidence strength: Preliminary — animal and mechanistic data only; no robust human interventional studies.
Many of threonine's functions are due to its presence as a residue of specific proteins, including collagen, elastin, and enamel. Threonine is a structural component of these key extracellular matrix proteins and also serves as a biochemical precursor for glycine and serine, which are themselves required for collagen biosynthesis. Threonine is also important for connective tissue and muscle strength and elasticity, and may improve wound healing and recovery from injury. Higher serum levels of threonine are associated with better healing outcomes in diabetic foot ulcer patients, though this is observational rather than interventional evidence.
Evidence strength: The structural role of threonine in collagen and elastin proteins is biochemically well-established; the therapeutic implication of supplementation on wound healing or connective tissue conditions in humans requires further clinical study.
Threonine is an immune stimulant because it promotes thymus growth and activity. Results from poultry research suggest that threonine might function as a nutrient immunomodulator in maintaining intestinal barrier function. In human and mammalian physiology, serine/threonine kinases control the epigenetic, transcriptional, and metabolic programs that determine T-cell function, providing a mechanistic basis for the amino acid's role in adaptive immunity. However, controlled human supplementation trials measuring immune endpoints are not well-established in the published literature.
Evidence strength: Mechanistic and preclinical; direct human trial evidence for immunological outcomes is limited.
Studies show that alterations in serum levels of amino acids, including serine and glycine (which require threonine for production), are linked to major depression. Researchers found that changes in levels of threonine, aspartate, asparagine, and serine may predict a patient's response to treatment with antidepressants by modulating amino acid levels. These findings are observational and based on amino acid profiling, not on controlled supplementation trials. Evidence strength: Preliminary and indirect.
High levels of threonine (together with two other amino acids) were associated with longevity, as measured by living to be at least 80 years old, according to a metabolomics study of 647 human individuals. During human evolution, a regulatory variant increased expression of acyl-CoA synthetase family member 3 (ACSF3), an enzyme involved in threonine catabolism. This variant, absent in non-human great apes, enhanced threonine metabolism, supporting higher basal metabolic rates and promoting skeletal growth. These findings are associative and evolutionary rather than interventional.
The WHO/FAO/UNU consultation estimated that the mean requirement for L-threonine in healthy adults is 15 mg/kg body weight per day, representing 1.05 g L-threonine per day for an adult weighing 70 kg. Adult humans require about 20 mg/kg body weight per day.
A key study in the American Journal of Clinical Nutrition used an indicator amino acid balance technique to more precisely characterize this requirement. The 1985 FAO/WHO/UNU threonine recommendation was found to be inadequate, and 15 mg/kg/day was determined to be sufficient to achieve mean indicator (leucine) amino acid balance. Fifteen healthy adults were randomly assigned to receive 7, 15, or 46 mg threonine·kg⁻¹·d⁻¹.
The usual consumption of L-threonine from dietary supply and supplements in the American general population is 3.64–4.47 g/day, a value thus largely above the mean requirement.
A randomized double-blind controlled clinical trial determined the safety and tolerability of L-threonine in graded doses in supplements for 4 weeks. Healthy male adults (mean age 42.9) ingested randomly placebo or different doses of L-threonine: 0, 3, 6, 9, or 12 g/day for 4 weeks using a crossover design.
The WHO-recommended daily intake is 15 mg/kg body weight per day (WHO, 2007), corresponding to 1050 mg for a 70-kg person. L-threonine has been used clinically with the aim of increasing glycine concentrations in the cerebrospinal fluid of patients to reduce spasticity. When given in amounts of 4.5 to 6.0 g/day for 14 days, no adverse clinical effects were noted.
L-Threonine is commercially available in free-form crystalline powder, capsules, and tablets. A maximum dose of 1150 mg/day for use as a food supplement was found acceptable from a safety viewpoint by the AESAN (Spanish food safety authority), also because it is in line with the daily requirement of L-threonine.
L-threonine is used in dietary supplements and nutritional products ingested by healthy consumers. A randomized double-blind controlled clinical trial evaluated the safety and tolerability of L-threonine used in graded doses in supplements for 4 weeks in healthy male adults who ingested either placebo or different doses (0, 3, 6, 9, or 12 g/day) in a crossover design. None of the anthropometric parameters measured, dietary intake, or biochemical parameters were affected by L-threonine supplementation, except a non-specific minor increase in plasma aspartate aminotransferase.
Side effects that have been reported include stomach upset, headache, nausea, and skin rash. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used for the treatment of multiple sclerosis, no side effects or toxic effects of threonine were identified in the 7.5 g/day trial.
Threonine deficiency is rare, as most people get enough of the amino acid in the foods they eat. However, people with an unbalanced diet, vegans, and vegetarians may not consume enough threonine foods, which can cause low levels of the amino acid. Essential amino acids like threonine play a vital role in the structure of bones, muscles, and skin. When there is insufficient intake, deficiency symptoms may include mood changes, irritability, confusion, and digestive problems.
Evidence indicates that excess threonine is converted to carbohydrate, liver lipids, and carbon dioxide. The upper safety limit for threonine is not well-established. The IOM found no data on apparently healthy humans given oral L-threonine supplements showing specific toxic thresholds.
For those with ALS, threonine may be a concern when it comes to lung function. In one double-blind study, 95 patients with ALS were given either BCAAs, L-threonine, or a placebo for 6 months. The outcome of this trial with respect to pulmonary function warrants caution in this specific population.
Excess L-threonine in the system can cause health problems, often related to causing an imbalance in other amino acids. This is consistent with the general principle that large doses of individual free amino acids can alter plasma amino acid ratios and compete for shared transport systems.
The degradation of threonine is impaired in the following metabolic disease: Combined malonic and methylmalonic aciduria (CMAMMA). Individuals with organic acidemia disorders affecting branched-chain amino acid or organic acid metabolism may have altered threonine catabolism, warranting specialist oversight.
No major pharmacokinetic drug–nutrient interactions specific to L-threonine have been well-documented in clinical literature. Perhaps the main use of threonine in the body is to produce glycine. If a glycine supplement is taken or sufficient glycine is obtained from food, less supplemental threonine may be required. The antispasticity drug baclofen and L-threonine share overlapping pharmacological targets in spinal inhibitory neurotransmission via glycinergic pathways; no formal interaction studies have been published, but combined use in spasticity patients has been discussed in the clinical trial literature.
Health conditions that L-threonine may help support.
L-Threonine has been evaluated in multiple clinical trials as a symptomatic treatment for ALS, based on its role as a glycine precursor to counteract excitatory neurotoxicity. However, controlled trials at 2–4 g/day for up to 12 months did not demonstrate meaningful slowing of ALS progression or symptom reduction, and one trial raised concerns about potential worsening of lung function. The hypothesis was scientifically grounded but the clinical evidence does not support efficacy.
L-Threonine is a structural residue within collagen and elastin molecules and serves as a metabolic precursor to glycine and serine, the two amino acids most abundant in collagen. Animal feeding studies demonstrate that threonine deficiency impairs structural protein synthesis in tissues such as skin, tendons, and cartilage. Its role is biochemically established, though direct human interventional trials specifically targeting connective tissue endpoints with isolated L-threonine supplementation are lacking.
L-Threonine is required for the synthesis of intestinal mucins, which form the mucus layer that shapes the gut microbiota habitat. Animal colitis studies show that diets enriched in threonine restore microbiota composition after disruption. Threonine deficiency has been shown to destabilize the gut microbial community. The mechanism is primarily indirect, via maintenance of the mucus matrix that supports beneficial microbial colonization.
L-Threonine is essential for intestinal mucin synthesis and maintaining mucosal barrier integrity. Dietary threonine restriction is directly linked to increased paracellular permeability in animal models, consistent with a leaky gut phenotype. A 2011 PubMed review established threonine as a critical nutrient for mucosal integrity and barrier function. Human-specific supplementation trials for increased intestinal permeability have not been published.
L-Threonine plays a lipotropic role in the liver, helping to regulate fat metabolism and prevent hepatic lipid accumulation. Animal studies demonstrate that threonine deficiency causes fatty liver via impaired lipid transport. Threonine is also catabolized in liver mitochondria to glycine, which participates in Phase II detoxification via glycine conjugation. Evidence is predominantly from animal and biochemical studies, not human clinical trials.
L-Threonine raises glycine levels in the central nervous system by serving as its precursor, and glycine is an inhibitory neurotransmitter in the spinal cord. Multiple double-blind, placebo-controlled trials have evaluated L-threonine for spinal spasticity, showing a modest but statistically significant antispastic effect. This is the best-supported clinical application of L-threonine supplementation.
L-Threonine is a direct structural residue in both collagen and elastin and is a precursor to glycine — the dominant amino acid in collagen. Animal studies confirm that threonine availability influences collagen abundance in skin. The mechanistic basis for a link to skin elasticity is well-established, though human interventional data specifically for L-threonine on skin outcome measures are absent.
Body systems that L-threonine may help support.
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