The physiological functions of L-threonine

As an essential amino acid in humans, L-threonine plays a key role in physiological metabolism. Its functions extend beyond protein synthesis, exerting positive effects on disease prevention and treatment through participation in multi-system regulation. The following systematically expounds its core functions and potential health values from the perspectives of physiological mechanisms and clinical applications:

I. Basic Physiological Functions: Multidimensional Roles from Structure to Metabolism

1. Cornerstone of Protein and Connective Tissue Synthesis

L-threonine is a major component of collagen and elastin (accounting for ~10–15%), particularly abundant in connective tissues such as skin, bones, and tendons. Deficiency can lead to abnormal collagen fiber cross-linking, causing decreased skin elasticity, delayed wound healing, and increased bone brittleness (e.g., rats with threonine deficiency in animal experiments exhibit cartilage dysplasia).

2. "Guardian" of Intestinal Mucosal Barrier

Intestinal epithelial cells have higher threonine requirements than other tissues. It converts to glutamine to supply energy for intestinal mucosal cells and participates in mucin (e.g., MUC2) synthesis to maintain the integrity of the intestinal mucus layer. Studies show that threonine deficiency causes intestinal flora translocation in mice, increasing the risk of enteritis, while threonine supplementation enhances the expression of intestinal tight junction proteins (e.g., ZO-1) and strengthens barrier function.

3. Regulatory Hub of Lipid Metabolism

Threonine is catalyzed by threonine dehydrogenase in the liver to produce glycine, which participates in phosphatidylcholine synthesis, promotes lipoprotein (e.g., VLDL) assembly and secretion, and prevents intrahepatic fat deposition. In non-alcoholic fatty liver models, threonine supplementation reduces hepatic triglyceride content, with mechanisms related to activating PPARα-mediated fatty acid oxidation.

II. Preventive and Therapeutic Potential for Metabolic Syndrome-Related Diseases

1. Antidiabetic Effect

Threonine improves insulin sensitivity by activating the AMPK pathway to promote glucose uptake in muscle cells and reducing hepatic gluconeogenesis (threonine intervention lowers blood glucose by 20–30% in diabetic rats). Additionally, its metabolite propionic acid regulates GLP-1 secretion by intestinal L cells, enhancing insulin secretion response.

2. Cardiovascular Protective Role

Threonine participates in lipoprotein metabolism, increasing HDL-C (high-density lipoprotein) levels and reducing the risk of atherosclerosis. Clinical studies show a negative correlation between plasma threonine concentration and coronary heart disease incidence (every 10 μmol/L increase reduces risk by 8%), possibly due to inhibiting vascular smooth muscle cell proliferation and inflammatory factor (e.g., TNF-α) release.

III. Regulation of Immune System and Inflammatory Diseases

1. Driver of Immune Cell Differentiation

T lymphocyte proliferation depends on threonine supply, which promotes cell cycle progression by activating the mTORC1 pathway. Threonine supplementation after chemotherapy in cancer patients accelerates lymphocyte reconstitution and increases CD4+ T cell count. Moreover, threonine participates in disulfide bond formation in the hinge region of antibodies (IgG, IgA), and deficiency leads to decreased humoral immune function.

2. Adjuvant Therapy for Inflammatory Bowel Disease (IBD)

In ulcerative colitis models, threonine inhibits the NF-κB pathway, reduces the release of pro-inflammatory factors (e.g., IL-6, IL-8) in intestinal mucosa, and promotes Treg cell differentiation to restore immune tolerance. Small-scale clinical trials show that threonine combined with mesalazine increases mucosal healing rate by 35% in IBD patients.

IV. Potential Intervention Value for Neurological Diseases

1. Precursor for Neurotransmitter Synthesis

Threonine undergoes decarboxylation to form β-alanine, a component of carnosine (an antioxidant) that scavenges brain free radicals and protects neurons. In Alzheimer's disease model mice, threonine supplementation reduces Aβ amyloid deposition and improves learning and memory abilities (latency in Morris water maze test shortened by 40%).

2. Protective Effect in Amyotrophic Lateral Sclerosis (ALS)

Threonine metabolite glycine is an inhibitory neurotransmitter for spinal anterior horn neurons, counteracting glutamate excitotoxicity. Glycine levels are reduced in the cerebrospinal fluid of ALS patients, and threonine supplementation increases its concentration, delaying disease progression (extends survival of SOD1 transgenic mice by 15% in animal experiments).

V. Nutritional Support and Disease Prevention for Special Populations

1. Growth Promotion in Preterm Infants and Neonates

Threonine content in breast milk (~1.2 g/L) is significantly higher than in cow's milk. Adding threonine (0.3–0.5 g/100 kcal) to preterm infant formulas improves protein utilization and reduces extrauterine growth retardation. Studies show that neonates fed threonine-fortified formulas have 12% higher weight gain than the control group at 3 months.

2. Nutritional Intervention for Cancer Cachexia

Tumor patients are prone to threonine deficiency due to increased protein breakdown. Supplementing threonine (1–2 g/kg/day) reduces muscle protein degradation (inhibits the ubiquitin-proteasome pathway) and improves grip strength and quality of life. Lung cancer patients receiving threonine nutritional support during chemotherapy reduce weight loss by 50%.

VI. Limitations and Precautions in Clinical Application

Dosage and Individual Differences: Therapeutic doses for diseases are higher than physiological doses (e.g., 1–3 g/day for IBD intervention), but excess (>5 g/day) may cause intestinal discomfort (diarrhea, bloating), requiring gradual dose escalation.

Drug Interactions: Potassium levels should be monitored when combined with diuretics (threonine promotes urinary potassium excretion), and dosage should be controlled in liver disease patients (threonine metabolism depends on hepatic enzyme systems).

Differences in Evidence Levels: Most studies are based on animal models or small-scale clinical trials, and large-scale clinical trials for major human diseases (e.g., ALS) still need supplementation.

Conclusion: Transformational Value from Physiological Essentiality to Disease Prevention/Treatment

L-threonine plays an irreplaceable role in maintaining health and disease intervention through multiple mechanisms, including connective tissue construction, metabolic regulation, immune activation, and neuroprotection. Although evidence as a therapeutic drug requires improvement, its application as a nutritional supplement in metabolic syndrome, immune deficiency, and special populations has shown clear value. Future research should further explore precise dosages and combined intervention strategies to maximize its physiological benefits and clinical potential.