L-Threonine

L-Threonine at a Glance

L-threonine is an essential amino acid found in meat, dairy, eggs and lentils. It was the last of the essential amino acids to be identified, in 1936.

What distinguishes it is where the body sends it: threonine is heavily concentrated in mucin, the glycoprotein that forms the protective mucus layer lining the gut. A large share of dietary threonine is consumed by the intestine itself before it ever reaches the bloodstream.

What It’s Used For

Correcting deficiency: gut mucin & barrier — restores mucin production and intestinal barrier integrity.
Immune / mucosal immunity support — supports mucosal immune function.
Spasticity (MS & spinal) — reduces spasticity in multiple sclerosis and spinal injury.

How It Works

Mucin is exceptionally rich in threonine — the amino acid provides the attachment points for the sugar chains that give mucus its gel structure. Because the gut extracts threonine for that purpose first, intestinal demand competes directly with the rest of the body, which is why threonine status shows up as a barrier-function problem before anything else.

Its neurological use runs through a different route: threonine is metabolised to glycine, an inhibitory neurotransmitter in the spinal cord, which is the rationale for raising spinal glycine to damp spasticity.

The full trial record is in Pharmacology & Research below.

Pharmacology & Research

L-Threonine is an essential (indispensable) amino acid — the body cannot make it, so all of it comes from dietary protein. Its decision-relevant biology is nutritional rather than pharmacological: it is a major building block of mucin, the threonine-rich glycoprotein that forms the protective mucus layer of the gut, and it feeds into glycine and serine metabolism. The evidence divides cleanly into two stories that are easy to conflate. The repletion/deficiency story — threonine limitation impairs gut mucin synthesis and barrier function — is well demonstrated, but almost entirely in animals and in the context of restriction, not supplementation on top of an adequate diet. The pharmacological story — high-dose L-threonine (4.5–7.5 g/day) as a glycine precursor to treat spasticity — produced statistically real but clinically trivial effects in small human trials from the early 1990s and has not advanced since. For a healthy person eating enough protein, standalone threonine supplementation has no established benefit.

Best-supported:Correcting dietary threonine deficiency restores intestinal mucin synthesis and gut barrier function — robust, but shown in animal models of restriction rather than in replete humans ^{7,9,11Reference 7Faure M et al. · 2005AnimalDietary threonine restriction specifically reduces intestinal mucin synthesis in rats — controlled animal studyView study →Reference 9Mao X et al. · 2011ReviewSpecific roles of threonine in intestinal mucosal integrity and barrier function — reviewView study →Reference 11Puiman PJ et al. · 2011Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs — animal studyView study →}.

Emerging / cautiously endorsed:High-dose oral L-threonine produces a small, statistically significant reduction in clinical signs of spasticity (MS and spinal), with the notable advantage of no sedation — but the effect is too small to be clinically useful ^{1,2,3Reference 1Growdon JH et al. · 1991RCTL-threonine in the treatment of spasticity — randomised double-blind crossover trialView study →Reference 2Lee A · 1993RCTA double-blind study of L-threonine in patients with spinal spasticity — randomised crossover trialView study →Reference 3Hauser SL et al. · 1992RCTAn antispasticity effect of threonine in multiple sclerosis — randomised crossover trialView study →}.

Popular but thin / overhyped:“Gut health,” collagen/skin, and immune-boosting claims for threonine supplements in well-nourished people rest on animal repletion data and mechanism, not human supplementation trials ^{10,16Reference 10Zhang H et al. · 2019L-threonine improves intestinal mucin synthesis and immune function of intrauterine growth-retarded weanling piglets — animal studyView study →Reference 16Lan A et al. · 2015ReviewMucosal healing in inflammatory bowel diseases: is there a place for nutritional supplementation? — reviewView study →}.

The honest miss / caveat:L-threonine failed to slow amyotrophic lateral sclerosis (ALS) and its antispastic effect, though real, was judged not clinically valuable by the investigators themselves ^{6,1Reference 6Parton M et al. · 2003Systematic reviewAmino acids for amyotrophic lateral sclerosis / motor neuron disease — systematic reviewView study →Reference 1Growdon JH et al. · 1991RCTL-threonine in the treatment of spasticity — randomised double-blind crossover trialView study →}.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric. Each application links down to its write-up.

Threonine is used disproportionately by the gut. Mucins — the gel-forming glycoproteins secreted by goblet cells — are exceptionally rich in threonine, so intestinal mucin synthesis is one of the first processes to suffer when dietary threonine is scarce. In rats, restricting dietary threonine to 30% of requirement specifically and significantly reduced mucin fractional synthesis rate in the duodenum, ileum, and colon, while leaving general mucosal protein synthesis intact — a targeted hit to the mucus barrier ^{7Reference 7Faure M et al. · 2005AnimalDietary threonine restriction specifically reduces intestinal mucin synthesis in rats — controlled animal studyView study →}.

A large fraction of dietary threonine is extracted by the gut on first pass and committed to mucin rather than oxidized, and this demand rises during intestinal inflammation ^{8,9Reference 8Rémond D et al. · 2009Intestinal inflammation increases gastrointestinal threonine uptake and mucin synthesis in enterally fed minipigs — animal studyView study →Reference 9Mao X et al. · 2011ReviewSpecific roles of threonine in intestinal mucosal integrity and barrier function — reviewView study →}.

In intrauterine-growth-retarded weanling piglets, 2 g/kg-diet L-threonine raised ileal Muc2, secretory IgA, and goblet-cell density and dampened inflammation ^{10Reference 10Zhang H et al. · 2019L-threonine improves intestinal mucin synthesis and immune function of intrauterine growth-retarded weanling piglets — animal studyView study →}.

The consistent theme: threonine is limiting for mucin production, so adding it back when intake is low restores barrier function. What is missing is any evidence that extra threonine helps a person already eating adequate protein — a systematic review of nutritional support for mucosal healing in inflammatory bowel disease found the supporting data for threonine (and other amino acids) came almost entirely from animal and cell studies, not human trials ^{16Reference 16Lan A et al. · 2015ReviewMucosal healing in inflammatory bowel diseases: is there a place for nutritional supplementation? — reviewView study →}.

Gap: The benefit is deficiency-dependent and demonstrated in animals; there is no human supplementation trial showing gut benefit in replete people.

This is the one genuinely pharmacological human use. The rationale: L-threonine is a precursor for glycine, an inhibitory neurotransmitter in the spinal cord, so raising threonine might enhance glycinergic inhibition of overactive motor reflexes. Three small double-blind trials tested it. In familial spastic paraparesis, 4.5–6.0 g/day produced a statistically significant (p < 0.02) decrease in spasticity ratings — but the authors concluded “the benefits were not clinically valuable,” and CSF glycine did not actually rise ^{1Reference 1Growdon JH et al. · 1991RCTL-threonine in the treatment of spasticity — randomised double-blind crossover trialView study →}.

In multiple sclerosis, 7.5 g/day reduced signs of spasticity on examination with no side effects and no sedation (a real contrast with baclofen and tizanidine), but again produced no symptomatic improvement the patient or physician could feel ^{3Reference 3Hauser SL et al. · 1992RCTAn antispasticity effect of threonine in multiple sclerosis — randomised crossover trialView study →}.

A third crossover trial at 6 g/day in spinal spasticity reported a “modest but definite” antispastic effect ^{2Reference 2Lee A · 1993RCTA double-blind study of L-threonine in patients with spinal spasticity — randomised crossover trialView study →}.

Later systematic reviews were unimpressed: a Cochrane review of anti-spasticity agents found the threonine data, like most in this field, methodologically weak ^{4Reference 4Shakespeare DT et al. · 2000Systematic reviewAnti-spasticity agents for multiple sclerosis — systematic reviewView study →}, and a dedicated MS systematic review concluded the single RCT “does not support its effectiveness” ^{5Reference 5Paisley S et al. · 2002Systematic reviewClinical effectiveness of oral treatments for spasticity in MS — systematic reviewView study →}.

Gap: Effect is statistically real but clinically negligible, glycine did not rise as hypothesized, and no trial has been run in over two decades.

Mechanisms

Target / pathway	Effect	Relevant to
Mucin (MUC2) synthesis in goblet cells	Substrate — threonine-rich glycoprotein; limiting for synthesis	Gut barriermucosal immunity
Spinal glycine (inhibitory neurotransmission)	Proposed precursor; ↑ glycinergic inhibition (glycine did not measurably rise in trials)	Spasticity
Glycine / serine one-carbon metabolism	Catabolic substrate via threonine dehydrogenase / threonine dehydratase	Systemic amino-acid metabolism
Protein synthesis (collagen, elastin, antibodies)	Incorporated as an indispensable residue; frequent O-glycosylation / phosphorylation site	Connective tissueimmune proteins

Pharmacokinetics

L-Threonine is absorbed in the small intestine via sodium-dependent neutral amino acid transporters. A defining feature is heavy first-pass gut extraction: roughly a quarter or more of an oral dose is taken up by the portal-drained viscera and liver before reaching the systemic circulation, and a large share of the gut’s uptake is committed to mucin synthesis rather than oxidation ^{8,11Reference 8Rémond D et al. · 2009Intestinal inflammation increases gastrointestinal threonine uptake and mucin synthesis in enterally fed minipigs — animal studyView study →Reference 11Puiman PJ et al. · 2011Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs — animal studyView study →}. It is metabolized primarily via threonine dehydratase and threonine dehydrogenase toward glycine, serine, and one-carbon units; unlike most amino acids it is not transaminated. Oral dosing raises plasma and CSF threonine, but — importantly for the spasticity rationale — this did not translate into measurably higher glycine levels in the human trials ^{1,3Reference 1Growdon JH et al. · 1991RCTL-threonine in the treatment of spasticity — randomised double-blind crossover trialView study →Reference 3Hauser SL et al. · 1992RCTAn antispasticity effect of threonine in multiple sclerosis — randomised crossover trialView study →}. No meaningful “half-life” is defined for a dietary amino acid; plasma levels track intake and clear over hours.

Clinical trials

Registered-trial activity for standalone L-threonine is minimal. It is off-patent, cheap, and of no commercial interest as a drug, so the human evidence is essentially frozen at the small neurology trials of the early 1990s plus the ALS amino-acid trials; the active research is in animal nutrition (swine/poultry feed), where threonine is a routine feed additive.

Completed	Planned	Terminated	Preclinical
~4(spasticity/ALS, small)	~0	0	many(animal-nutrition)

Last checked: July 2026.

Dietary Sources

L-Threonine is supplied by virtually all dietary protein; deficiency is essentially unknown in people eating adequate protein. It is relatively abundant in animal proteins and concentrated in some plant sources, while being a limiting amino acid in cereal grains — one reason grain-heavy diets historically paired grains with legumes.

Food (per typical serving)	Approx. threonine
Lean beef / poultry (100 g)	~1.2–1.4 g
Fish (100 g)	~0.9–1.1 g
Eggs (2 large)	~0.6 g
Cottage cheese / dairy (100 g)	~0.5–0.7 g
Lentils / beans, cooked (1 cup)	~0.6–0.7 g
Soy / tofu (100 g)	~0.5–0.7 g
Wheat / rice (limiting AA)	low relative to needs

A mixed diet providing adequate total protein delivers roughly 2–2.5 g of threonine per day, comfortably above the ~1 g/day physiological requirement. Refining grains lowers protein and threonine content; the amino acid is otherwise stable in ordinary cooking. See the NIH ODS and dietary-reference literature for authoritative food composition.

Intake & Dosage

Physiological requirement. Threonine is an indispensable amino acid. Modern stable-isotope (indicator amino acid oxidation) studies in adults converge on a mean requirement of about 15 mg/kg/day — roughly 1.0–1.1 g/day for a 70 kg adult — which is about double the older 1985 FAO/WHO nitrogen-balance figure of 7 mg/kg/day that those studies specifically overturned ^{13,14,15Reference 13Wilson DC et al. · 2000Threonine requirement of young men determined by indicator amino acid oxidation — human metabolic studyView study →Reference 14Borgonha S et al. · 2002Threonine requirement of healthy adults, derived with a 24-h indicator amino acid balance technique — human metabolic studyView study →Reference 15Kurpad AV et al. · 2002Threonine requirements of healthy Indian men, measured by a 24-h indicator amino acid oxidation and balance technique — human metabolic studyView study →}. One study in young men put the upper safe intake near 26 mg/kg/day ^{13Reference 13Wilson DC et al. · 2000Threonine requirement of young men determined by indicator amino acid oxidation — human metabolic studyView study →}. This requirement is met by any adequate-protein diet.

Supplemental / research doses. There is no established reason to supplement threonine on top of an adequate diet. The doses studied in humans were pharmacological, for spasticity: 4.5–7.5 g/day ^{1,2,3Reference 1Growdon JH et al. · 1991RCTL-threonine in the treatment of spasticity — randomised double-blind crossover trialView study →Reference 2Lee A · 1993RCTA double-blind study of L-threonine in patients with spinal spasticity — randomised crossover trialView study →Reference 3Hauser SL et al. · 1992RCTAn antispasticity effect of threonine in multiple sclerosis — randomised crossover trialView study →}. Amino-acid blends and sports formulas include threonine at fractions of a gram. For minerals one would specify elemental weight; that does not apply here — L-threonine is a single free amino acid (molecular weight ≈ 119 g/mol), so the labeled amount is the compound itself.

These are doses studied in research, not a personal recommendation. A varied diet with adequate protein already supplies more threonine than the body requires.

Safety

L-Threonine is a dietary essential with an unusually quiet safety profile — even the multi-gram doses used in the spasticity trials produced little more than mild gut upset. The honest caveat is how little has been formally studied rather than any documented harm.

Safety at a Glance

Low / no toxicity

Well tolerated at studied doses. Up to 7.5 g/day for weeks caused only minimal side effects, with no sedation or motor weakness.
No documented drug interactions. Threonine is not a CYP450 substrate — though this reflects an absence of reports, not proven absence.
Mild gastrointestinal effects at high doses. Nausea and loose stools.
No Upper Intake Level is set. The absence of a limit is not evidence that very high chronic intakes are safe.
Supplemental doses unstudied in pregnancy and breastfeeding. Diet is safe; gram-level supplements are not established — see the box below.

Full Safety & Interactions Detail

L-Threonine is well tolerated. As a normal dietary constituent it carries no concern at food-level intakes, and the multi-gram doses used in the spasticity trials (up to 7.5 g/day for weeks) produced only minimal side effects, with no sedation or motor weakness — a contrast the MS investigators specifically highlighted against conventional antispastic drugs ^{1,3Reference 1Growdon JH et al. · 1991RCTL-threonine in the treatment of spasticity — randomised double-blind crossover trialView study →Reference 3Hauser SL et al. · 1992RCTAn antispasticity effect of threonine in multiple sclerosis — randomised crossover trialView study →}.

Reported effects at high doses are mild and gastrointestinal (nausea, loose stools). Very high sustained intakes can raise plasma threonine (hyperthreoninemia); this has been studied mainly in developing animals and is not an established human concern at dietary or trial doses. No clinically significant drug interactions are documented, and threonine is not a substrate for the CYP450 drug-metabolizing enzymes; formal interaction studies are lacking, so this reflects an absence of reports rather than proven absence. No Tolerable Upper Intake Level is set for individual amino acids, threonine included — the absence of a limit is not evidence that very high chronic intakes are safe.

Pregnancy & Lactation

Caution in pregnancy Caution while breastfeeding

Verdict: not formally established — treat dietary intake as safe, supplemental high doses as unstudied. Threonine from food is essential and safe throughout pregnancy and lactation, and requirements rise modestly. There are no controlled trials of high-dose L-threonine supplementation in pregnant or breastfeeding women, so gram-level supplementation should not be assumed safe. Anyone pregnant or breastfeeding should get threonine from a balanced diet rather than isolated supplements unless directed by a clinician. This is general information, not medical advice; individual decisions should be made with a qualified healthcare professional.

References

Growdon JH, Nader TM, Schoenfeld J, Wurtman RJ. (1991). L-threonine in the treatment of spasticity — randomised double-blind crossover trial. Clin Neuropharmacol. https://pubmed.ncbi.nlm.nih.gov/1742749/
Lee A, Patterson V. (1993). A double-blind study of L-threonine in patients with spinal spasticity — randomised crossover trial. Acta Neurol Scand. https://pubmed.ncbi.nlm.nih.gov/8296531/
Hauser SL, Doolittle TH, Lopez-Bresnahan M, et al. (1992). An antispasticity effect of threonine in multiple sclerosis — randomised crossover trial. Arch Neurol. https://pubmed.ncbi.nlm.nih.gov/1520082/
Shakespeare DT, Young CA, Boggild M. (2000). Anti-spasticity agents for multiple sclerosis — systematic review. Cochrane Database Syst Rev. https://pubmed.ncbi.nlm.nih.gov/11034714/
Paisley S, Beard S, Hunn A, Wight J. (2002). Clinical effectiveness of oral treatments for spasticity in MS — systematic review. Mult Scler. https://pubmed.ncbi.nlm.nih.gov/12166503/
Parton M, Mitsumoto H, Leigh PN. (2003). Amino acids for amyotrophic lateral sclerosis / motor neuron disease — systematic review. Cochrane Database Syst Rev. https://pubmed.ncbi.nlm.nih.gov/14583978/
Faure M, Moënnoz D, Montigon F, et al. (2005). Dietary threonine restriction specifically reduces intestinal mucin synthesis in rats — controlled animal study. J Nutr. https://pubmed.ncbi.nlm.nih.gov/15735082/
Rémond D, Buffière C, Godin JP, et al. (2009). Intestinal inflammation increases gastrointestinal threonine uptake and mucin synthesis in enterally fed minipigs — animal study. J Nutr. https://pubmed.ncbi.nlm.nih.gov/19193812/
Mao X, Zeng X, Qiao S, Wu G, Li D. (2011). Specific roles of threonine in intestinal mucosal integrity and barrier function — review. Front Biosci (Elite Ed). https://pubmed.ncbi.nlm.nih.gov/21622125/
Zhang H, Chen Y, Li Y, et al. (2019). L-threonine improves intestinal mucin synthesis and immune function of intrauterine growth-retarded weanling piglets — animal study. Nutrition. https://pubmed.ncbi.nlm.nih.gov/30504005/
Puiman PJ, Jensen M, Stoll B, et al. (2011). Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs — animal study. J Nutr. https://pubmed.ncbi.nlm.nih.gov/21593357/
Wellington MO, Hamonic K, Krone JEC, et al. (2020). Effect of dietary fiber and threonine on intestinal barrier function in challenged pigs — animal study. J Anim Sci Biotechnol. https://pubmed.ncbi.nlm.nih.gov/32318266/
Wilson DC, Rafii M, Ball RO, Pencharz PB. (2000). Threonine requirement of young men determined by indicator amino acid oxidation — human metabolic study. Am J Clin Nutr. https://pubmed.ncbi.nlm.nih.gov/10702170/
Borgonha S, Regan MM, Oh SH, Condon M, Young VR. (2002). Threonine requirement of healthy adults, derived with a 24-h indicator amino acid balance technique — human metabolic study. Am J Clin Nutr. https://pubmed.ncbi.nlm.nih.gov/11916756/
Kurpad AV, Raj T, Regan MM, et al. (2002). Threonine requirements of healthy Indian men, measured by a 24-h indicator amino acid oxidation and balance technique — human metabolic study. Am J Clin Nutr. https://pubmed.ncbi.nlm.nih.gov/12324292/
Lan A, Blachier F, Benamouzig R, et al. (2015). Mucosal healing in inflammatory bowel diseases: is there a place for nutritional supplementation? — review. Inflamm Bowel Dis. https://pubmed.ncbi.nlm.nih.gov/25208104/