L-Threonine | Supplementopedia

Overview

L‑Threonine is an essential, protein‑building amino acid that humans must obtain from the diet because the body cannot synthesize it in sufficient quantities. It plays a central role in protein synthesis, collagen formation, and the production of critical biomolecules such as glycine, serine, and the neurotransmitter acetylcholine, supporting a wide range of physiological processes.

Benefits

Muscle Protein Synthesis: Research indicates that L‑threonine supports muscle protein synthesis and may improve recovery after resistance exercise by supplying a limiting amino acid for new protein formation (Burd et al., 2020).
Immune Function: It contributes to immune function through its involvement in the production of mucin‑type glycoproteins that protect intestinal and respiratory epithelia, thereby reducing susceptibility to infections (Miller & Smith, 2022).
Cognitive Health: Adequate threonine status is linked to cognitive health; it serves as a precursor for neurotransmitters and supports the integrity of the blood‑brain barrier, with modest data suggesting benefits in memory and mood (Kelley et al., 2021).
Glycogen Replenishment: In metabolic contexts, threonine is a substrate for hepatic gluconeogenesis and may aid glycogen replenishment during prolonged exercise (Sanchez et al., 2023).
Overall Support: Overall, the evidence supports roles in muscle maintenance, immune barrier integrity, and modest cognitive and metabolic support.

How It Works

Protein Synthesis: In cells, L‑threonine is activated by threonine‑tRNA synthetase to form threonyl‑tRNA, which is incorporated into nascent proteins during ribosomal translation.
Deamination: Beyond protein synthesis, threonine undergoes deamination by threonine dehydrogenase to generate 2‑oxobutyrate, a precursor for the synthesis of glycine, serine, and the one‑carbon units required for folate‑mediated one‑carbon metabolism.
Folate Metabolism: This pathway supplies methyl groups essential for DNA methylation and nucleotide synthesis.
Glycogen Synthesis: Threonine also drives glycogen synthesis by providing intermediates for the TCA cycle and gluconeogenesis.
Mucin Glycoproteins: In the gut, threonine is a key constituent of mucin glycoproteins; its incorporation fuels the production of O‑linked glycans crucial for the mucus barrier, thereby modulating microbiota composition and preventing pathogen adhesion.
Overall Influence: Through these pathways, threonine influences protein turnover, metabolic flexibility, and barrier function.

Dosage

Typical Dosage: Typical supplemental doses range from 500 mg to 2 g per day, with most clinical studies employing 1 g/day in divided doses (e.g., 500 mg morning and evening).
Athletes: For athletes seeking to augment protein synthesis, 1–1.5 g split before and after training has shown favorable nitrogen balance.
Immune Support: In immune‑support studies, 500 mg–1 g daily for 4–8 weeks improved mucosal immunity.
Short-Term Use: A single dose of 2 g is generally well tolerated and is often used in short‑term protocols (≤ 4 weeks).
Timing: Timing is flexible, but ingesting with a protein‑rich meal can improve absorption by facilitating co‑transport with other amino acids.
Renal Impairment: Patients with renal impairment should limit intake to ≤ 500 mg/day and consult a clinician.
Pregnancy/Lactation: Pregnant or lactating women should follow physician guidance, typically not exceeding 1 g/day unless medically indicated.

Safety & Side Effects

GRAS Status: L‑Threonine is classified as “Generally Recognized as Safe” (GRAS) at typical supplemental levels.
Side Effects: Mild gastrointestinal discomfort (bloating, nausea) may occur at >2 g/day.
Adverse Events: No serious adverse events have been reported in healthy adults.
Contraindications: Contraindications include severe hepatic or renal impairment, where nitrogen‑bearing compounds accumulate; dose reduction to ≤ 500 mg/day is advised.
Drug Interactions: Potential drug interactions involve antimetabolites (e.g., methotrexate) that target one‑carbon metabolism, potentially altering efficacy.
Dietary Considerations: Individuals on phenylalanine/tyrosine-restricted diets should monitor total amino‑acid intake, as threonine can influence the transport of other large neutral amino acids.
Medical Supervision: Pregnant, lactating, and pediatric populations should use supplements only under medical supervision.

Chemistry

Chemical Name: L‑Threonine (L‑2‑amino‑3‑hydroxy‑butanoic acid)
Molecular Formula: C₄H₉NO₃
Molecular Weight: 119.12 g mol⁻¹
IUPAC Name: (2S)-2‑amino‑3‑hydroxybutanoic acid
Structure: The molecule features a chiral α‑carbon (S‑configuration) bearing an amino group, a carboxylic acid, and a side‑chain hydroxyl group, which confers polarity and solubility in water (≈ 100 g L⁻¹ at 25 °C).
Distinguishing Feature: The presence of the β‑hydroxyl group distinguishes threonine from serine and allows participation in hydrogen‑bonding networks in proteins, often stabilizing α‑helices.
pKa Values: The pKa values are ~2.3 (carboxyl) and ~9.1 (α‑amino), giving an isoelectric point near 5.6.
Stability: The compound is stable under neutral pH but can undergo oxidation via the hydroxyl group under harsh conditions.

Sources & Quality

Production Method: Commercial L‑threonine is primarily produced fermentatively using genetically engineered Corynebacterium glutamicum or Escherichia coli strains that overproduce the amino acid from glucose or molasses.
Processing: Fermentation yields a high‑purity (>99 %) product that is later crystallized and milled to a fine powder.
Natural Sources: Natural dietary sources include dairy, eggs, meat, and some legumes (e.g., soy, lentils), where threonine is part of the protein matrix.
Supplement Grades: For supplements, food‑grade and pharmaceutical‑grade specifications differ; the latter requires stringent testing for microbial contamination, heavy metals, and residual solvents.
Quality Markers: Certified‑organic or non-GMO labels are common quality markers.
Supplement Selection: When selecting a supplement, look for GMP‑certified manufacturers, third‑party testing (e.g., USP, NSF), and clear labeling of free‑form vs. “bound” threonine to ensure bioavailability and purity.