Threonine

Threonine is a nutrient belonging to the essential amino acid class.

Threonine is also known as thr or th, L-Threonine and 2-Amino-3-hydroxybutanoic acid.

Threonine is vital for maintaining overall well-being as it promotes protein synthesis, immunological function, and the body's ability to produce critical substances like collagen and neurotransmitters.

Threonine deficiency is rare and can cause symptoms, including digestive issues, emotional instability or irritability, disorientation, increased liver fat, and poor nutritional absorption.

Threonine may be found naturally in both plant and animal sources. Plant-based sources include legumes like beans, lentils, and soy products, as well as grains like quinoa and whole wheat. Animal sources of threonine include lean meats like organic meat (chicken, lamb, beef and turkey), eggs, fish(salmon), and dairy products such as yoghurt and cottage cheese.

Threonine is absorbed in the small intestine, transported to tissues for protein synthesis, metabolised in the liver, and excess is eliminated through the kidneys via urine.

The common side effects of Threonine include stomach upset, headache, nausea, and skin rash.

Threonine is available in tablets, capsules and oral powders.

Biochemical action of Threonine

Threonine, belonging to the essential amino acid class, acts in several metabolism processes. It works via the mTOR (mechanistic target of rapamycin) signalling pathway.

Threonine is an essential amino acid that serves as a precursor to glycine and serine, which are used to synthesise nucleotides and collagen. As a lipotropic, it increases nutrition absorption and regulates liver fat accumulation. Its health benefits extend to the liver, brain, and digestion, helping synthesise proteins and various metabolic processes. The mTOR signalling system that regulates cell growth, proliferation, and protein synthesis has been significantly affected by threonine. Threonine is also required to produce glycine, which is essential for the collagen in connective tissue, and serine, which is necessary for synthesising nucleotides and phospholipids. Beyond its fundamental function, threonine helps facilitate the production of neurotransmitters, particularly glycine, which promotes inhibitory effects and optimum neurotransmission in the nervous system.

Threonine is available in tablets, capsules and oral powders.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.

Threonine can be used as a supplement when the threonine taken through diet is insufficient.

Taking threonine supplements effectively treats threonine deficiency caused by specific genetic diseases or other disorders.

Supplemental threonine may help with T-cell generation, immunological response, and the body's ability to fight against infections.

Supplemental threonine may be required to increase glutathione synthesis, which helps the body detoxify toxic chemicals.

Threonine improves the liver's normal functioning when taken as a supplement.

Threonine supplementation contributes to the production of collagen, which promotes the healing of wounds and injuries.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Threonine can help to support as a supplement for the following health benefits:

• Immune System: Threonine is essential for supporting the immune system. Threonine is necessary for the thymus gland to produce T lymphocytes (T-cells), which fight infections and are located close to the collarbones. Sufficient threonine promotes good immune function by supporting the development of T cells, which are essential for combating internal diseases.
• Digestion: Threonine stimulates the production of mucin, a protective substance in the digestive system, which helps in digestion. Supporting intestinal health and mucosal lining integrity is necessary for the proper functioning of the gastrointestinal barrier and the absorption of nutrients.
• Nerve Disorders: Threonine is present in large quantities in the central nervous system. By elevating glycine levels, threonine supplements showed potential for use in ALS therapy. Threonine provides prospective benefits for multiple sclerosis (MS), a different neuromuscular condition, instead of straight glycine supplementation, which does not successfully permeate the CNS. Threonine may also help with depression caused by leaky gut syndrome or food allergies, according to research, which contributes to its significance in promoting mental wellness.
• Collagen: Threonine is required for glycine biosynthesis, an essential process in collagen production. A structural protein, collagen, is present in bones, skin, and connective tissues. The synthesis of collagen supports skin health, accelerates wound healing, and maintains the integrity of numerous tissues, which is facilitated by sufficient threonine levels.
• Metabolic process: Threonine is a crucial component of several critical metabolic processes, including the mTOR signalling system. mTOR regulates protein synthesis, cell proliferation, and growth, which affects cellular development and overall function. The availability of threonine influences the mTOR pathway's activity, which influences vital processes, including immune response, muscle growth, and tissue repair.
• Prevent Fatty Liver: Threonine facilitates the transport and metabolism of lipids, restricting excessive fat buildup in the liver. It supports lipid metabolism and controls the amount of fat in the liver, helping treat or manage fatty liver disease. Fat can accumulate due to insufficient threonine, which could eventually result in liver failure.

Threonine supplementation may be administered orally.

Orally: Threonine supplements are available as tablets, capsules and powders that can be taken orally. Threonine supplements should be taken with meals or in combination with other nutrients in the meal to boost absorption and enhance amino acid utilisation.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 500 mg
• Capsules: 500mg
• Powder, oral: 2000 mg

Dosage Adjustment for Adult Patients

BY MOUTH:

6 grams of threonine per day is recommended for a specific movement problem (spinal spasticity) caused by spinal cord injury.

Threonine is available in tablets, capsules and oral powders

Threonine should be a supplement that helps in several metabolic processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.

• Stay within your daily calorie needs.

• Keep away from high-protein meals and beverages, especially those that include other amino acids, since these may hinder the absorption of threonine.

• Avoid eating excessive amounts of high-protein meals, especially those high in threonine, when taking threonine supplements since this can lead to an amino acid imbalance and may hinder absorption.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of threonine is 15 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of threonine is not established.

Threonine supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to threonine or other amino acids-related allergies
• Chronic liver disorder
• Chronic kidney disease (CKD)
• Kidney failure
• Metabolic disorders, such as homocystinuria and maple syrup urine disease
• Hyperammonemia

Prolonged and high doses of threonine supplements should be avoided in pregnancy, breastfeeding and children.

Before taking threonine, individuals with renal or liver disorders should see a physician since the dosage may need to be adjusted to prevent harmful effects.

Threonine supplements should not be given to those individuals who are on antidepressant medications as they might impact neurotransmitter levels and could interact with these medications.

Individuals with existing Amyotrophic lateral sclerosis (Lou Gehrig's disease) may use threonine cautiously, as prolonged use of this supplement might decrease the function of the lungs.

It is recommended to adhere to the dose recommended by the physician in order to prevent

any potential adverse effects.

To avoid potential interactions, it is recommended to use only one amino acid supplement or dietary supplements.

There is no sufficient scientific evidence regarding the use and safety of threonine for breastfeeding populations.

There is no sufficient scientific evidence regarding the use and safety of threonine for pregnant populations.

While taking threonine supplements, limit the consumption of high-protein meals, such as those high in threonine and alcoholic beverages, as they could hinder absorption.

The adverse reactions related to cysteine can be categorised as:

• Common: GI disturbances like bloating, gas, nausea, diarrhoea, vomiting and allergic reactions.
• Less Common: Headache and dizziness.
• Rare: Neurological effects and elevated amino acids.

The clinically relevant drug interactions of threonine are summarized here:

• NMDA antagonists: Memantine is a drug used to treat Alzheimer's disease symptoms. There are some concerns that threonine might decrease the effectiveness of Alzheimer's disease treatment.

The common side of threonine includes the following:

• Headache
• Vomiting
• Upset stomach
• Stomach cramps
• Diarrhea
• Nausea
• Skin rash

Threonine should be prudent in the following group of special populations.

• Pregnancy:

There is no sufficient scientific evidence traceable regarding the use and safety of threonine for pregnant populations. Avoid threonine supplements unless advised to do so by a healthcare professional while pregnant.

• Paediatrics:

Children's diet should contain adequate threonine-rich foods as it can help in overall growth, immunity, and mental health. However, there haven't been any appropriate studies conducted to date that haven't shown issues specific to children that would restrict the usage and safety of threonine in paediatric populations.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics:

Consuming sufficient threonine through a balanced diet or supplements can help older adults maintain their immune, cognitive function, and joint mobility. However, there is no adequate scientific evidence traceable regarding the use and safety of threonine for geriatric populations. Avoid supplements unless advised to do so by a healthcare professional.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of threonine for lactating mothers populations. Avoid threonine supplements unless advised by a healthcare professional while lactating.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of threonine. Overconsumption of threonine may lead to symptoms that might include headache, stomach upset, nausea, skin rash and fatty liver, formation of excess urea, disruption of amino acid balance and metabolic processes.

There is no specific antidote or treatment for excessive intake of supplemental threonine.

Threonine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after threonine supplement use or dietary intake. Fluid intake should be increased along with electrolyte monitoring. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of Threonine

Threonine is an essential α-amino acid. Its molecular structure consists of a central carbon atom attached to an amino group, a carboxyl group, and a side chain containing a hydroxyl (-OH) group. The hydroxyl group in threonine is the component that gives it a distinctive chemical structure. As threonine has a hydroxyl group on its side chain, it is categorised as a polar, uncharged amino acid. It gets integrated into proteins during translation, contributing to the structure and functionality of the resultant polypeptide chains.

The human body cannot produce threonine, so it must be acquired through dietary sources. It contributes to the formation of other significant substances, including glycine and serine, which are necessary for the production of collagen and the synthesis of nucleotides. Also, threonine has a role in the control of immunological and protein metabolism. Its hydroxyl group has the potential to be phosphorylated, which activates signalling pathways. Thus, threonine's numerous functions have significance in maintaining overall health and healthy physiological function.

Kinetic profile:

• Absorption: Threonine-containing proteins undergo breakdown into their component amino acids during digestion with the help of the enzymes in the stomach and small intestine. Threonine is absorbed from the small intestine via specialised transport systems, where it is transported across the intestinal lining and into the circulation.
• Distribution: Once threonine is absorbed, it is circulated to various tissues and cells via the bloodstream. It plays a crucial role in forming and functioning muscles, organs, and tissues by serving as a critical building block for protein synthesis.
• Metabolism: Threonine undergoes metabolic processes in the liver. Other amino acids like glycine and serine can be synthesised from it. Also, threonine takes part in several metabolic processes that lead to the formation of significant molecules like acetyl-CoA, which is necessary for the synthesis of fatty acids and energy-producing molecules.
• Elimination: Excess threonine and waste products are eliminated from the body through the kidneys via urine.

1. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf

2. https://www.ncbi.nlm.nih.gov/mesh/68013912

3. Chen G, Wang J. Threonine metabolism and embryonic stem cell self-renewal. Curr Opin Clin Nutr Metab Care. 2014 Jan;17(1):80

4. https://www.ncbi.nlm.nih.gov/books/NBK557845