Methionine

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

Methionine is also known L-methionine, D-methionine, DL-methionine, L-2-amino-4-(methylthio) butyric acid.

Methionine is an essential amino acid that the body needs to make several vital compounds. These substances are necessary for your cells to function properly.

A deficiency of Methionine may lead to conditions like homocystinuria (a genetic disorder that leads to elevated homocysteine levels in the blood) or hypomethioninemia. It is characterized by symptoms which might include hair loss, hepatic dysfunction, poor skin tone and toxic elevation of metabolic waste products.

Plants and animals are both sources of methionine.

Plant sources include legumes, whole grains, nuts, seeds, fruits, and green leafy vegetables. Meat (chicken, turkey, beef, and hog), fish, eggs (especially egg whites), and dairy (milk, cheese, and yoghurt) are all sources of animal protein.

In the small intestine, methionine is absorbed and transported throughout the body for protein synthesis and cellular processes. Its metabolism includes methylation and transsulfuration pathways, influencing gene expression and detoxification. Homocysteine and other related metabolites are excreted predominantly.

The common side effects of Methionine include digestive disturbances, nausea nausea and fever.

Methionine is available in tablets, capsules and oral powders.

Biochemical action of Methionine

Methionine belonging to the supplement class, acts in several biochemical processes. It works via DNA methylation, protein methylation, and the one-carbon metabolism pathway.

Methionine, an essential amino acid, is vital to many metabolic reactions within the body. One of its leading roles is to act as a precursor for the production of S-adenosylmethionine (SAMe), a significant methyl donor in various methylation processes. Methylation is an essential process that affects several metabolic pathways, gene expression, and protein function. The methylation of DNA, RNA, proteins, and other molecules by SAMe impacts physiological processes such as neurotransmitter synthesis, detoxification, and histone changes.

Additionally, methionine facilitates the folate cycle, a mechanism for one-carbon metabolism. Methionine is converted into S-adenosylhomocysteine (SAH), which is then changed into homocysteine. The two possible routes for homocysteine from there are transsulfuration to produce cysteine or remethylation to regenerate methionine. Numerous cofactors and enzymes, including vitamin B12, folate, and vitamin B6, control this metabolic path.

As the starting amino acid for translation, methionine is also crucial for the production of proteins. It acts as the first amino acid absorbed into the expanding polypeptide chain during protein synthesis. The transfer RNA (tRNA) molecule specific for methionine is linked to methionine by the enzyme methionyl-tRNA synthetase, which facilitates this process.

Methionine 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.

Methionine can be used as a supplement when the amount of Methionine taken from the diet is insufficient.

Taking Methionine supplements orally may effectively treat Methionine deficiency caused by specific genetic diseases or other disorders.

Methionine supplements may help promote stress adaption mechanisms, improve cognitive function, and treat depression or reward deficient syndrome linked to noradrenaline or dopamine depletion.

When used as a supplement, Methionine may help in lowering the pH of urine.

Methionine supplements may support the proper functioning of the liver, helping in detoxifying harmful substances.

Vitamins and natural supplements should not replace a balanced diet.

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

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

• Acetaminophen Overdose: Methionine treats acetaminophen overdose, a common over-the-counter pain medication. Rapid intervention, such as oral methionine within 10 hours, is critical to preventing liver damage or death caused by excessive acetaminophen consumption. The mechanism of methionine aims to protect the liver against acetaminophen metabolites. While methionine is possible, other therapies are available, and its effectiveness for acetaminophen overdose varies.
• Cancer Risk: The potential impact of methionine on cancer risk provides conflicting data. A 2013 meta-analysis linked dietary methionine to a lower risk of colon cancer, attributed to the formation of S-adenosyl methionine (SAMe), which regulates inflammation, cancer pathways, and cell death. However, results differ; some studies suggest limiting methionine lowers cancer risk. A 2020 review emphasized methionine's function in the proliferation of specific cancer cells and its potential for inhibition. Human trials are required to validate methionine's involvement, and it should not be used to reduce cancer risk until this is confirmed.
• Liver Damage: Combining methionine with medicines may help improve liver damage. Methionine supplementation may raise SAMe levels, hence protecting the liver. These findings, however, are being challenged, requiring further investigation for validation.
• Cobalamin deficiency: Long-term exposure to nitrous gas, used for anesthetic during the surgery, may result in adverse effects similar to cobalamin deficiency. Some study suggests that consuming methionine orally before surgery may lessen these nitrous oxide adverse effects.
• Antioxidant production: Numerous reactive oxygen species efficiently react with methionine residues in proteins to create methionine sulfoxide, scavenging reactive oxygen species. Methionine sulfoxide reductases are found in most cells and catalyze the thioredoxin-dependent reduction of methionine sulfoxide back to methionine. As a result, methionine residues may act as catalytic antioxidants, preserving both the protein and other macromolecules.
• Neural tube congenital disabilities: Other nutrients, including maternal folic acid, are thought to help prevent neural tube abnormalities (NTDs). Evidence demonstrates that methionine works with folic acid and vitamin B(12) to methylate contractile proteins involved in neural fold closure. However, the function of methionine in NTD risk has yet to be well investigated, and the findings suggest that increasing maternal dietary methionine intake may protect against NTDs.
• Parkinson's disease: The relationship between methionine and Parkinson's disease involves complex metabolic pathways. Homocysteine, a methionine metabolite, may contribute to oxidative stress and neurodegeneration in Parkinson's disease. However, more research is needed to determine its precise function in the condition and its treatment implications.

Methionine supplementation may be administered orally.

Orally: Methionine supplements are available as tablets and capsules that can be taken orally. The best time to take Methionine supplements is with meals, as it might enhance absorption and help prevent any potential gastrointestinal discomfort. It can be taken before or after a meal containing protein sources to provide the body with the context required to metabolise methionine properly.

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: 400 mg, 550 mg
• Capsules: 355 mg, 500mg, 1000 mg
• Powders, oral: 500mg, 1000 mg

Dosage Adjustment for Adult Patients

BY MOUTH:

For acetaminophen (Tylenol) poisoning- 2.5 g of methionine should be administered every 4 hours for 4 doses to prevent damage to liver and death. Methionine must be given within 10 hours of taking the acetaminophen.

Methionine is available in tablets, capsules and oral powders.

Methionine should be used as a supplement that helps in several biological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Limiting fried and grilled foods
• Limit foods like saturated fat, processed meats, and other protein supplements and drinks.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of methionine is 10 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL set for Methionine is not established.

Methionine supplementation may be contraindicated in the following conditions:

• Hypersensitivity; sensitive to Methionine or related compounds.
• Chronic liver disease, including cirrhosis:
• Kidney disease.
• Parkinson’s disease
• Homocystinuria
• Acidosis
• Atherosclerosis
• Methylenetetrahydrofolate reductase (MTHFR) deficiency

High doses of Methionine supplements should be cautiously used in individuals with peptic ulcers or gastritis.

It is suggested to exercise caution while taking supplements since they might increase calcium excretion in the urine in individuals with osteoporosis.

Methionine supplements should be used with caution by people with schizophrenia, as high dosages may result in disorientation, agitation, and other symptoms.

High methionine intake requires an increased intake of methyl-donating nutrients like B vitamins, betaine and choline, as without these additional nutrients, homocysteine levels can grow in the blood.

Caution is advised when consuming alcohol with Methionine.

There is no sufficient scientific evidence traceable regarding the use and safety of Methionine for use in special populations.

There is no sufficient scientific evidence traceable regarding the use and safety of Methionine for use in special populations.

Limit the consumption of foods and beverages higher in added sugars, saturated fat, processed meats, and caffeine, as these substances could hinder Methionine absorption.

The adverse reactions related to methionine can be categorized as-

• Common: GI disturbances like bloating, gas, nausea, diarrhoea, nausea or vomiting
• Less Common: Headache or dizziness.
• Rare: Allergic reactions (rash, itching) and elevated levels of homocysteine in the blood.

The clinically relevant drug interactions of Methionine are briefly summarized here:

• Antioxidants: Methionine could work in synergy with other antioxidants.
• Vitamins (Folic Acid, Vitamin B6, Vitamin B12): Methionine works with these nutrients to control homocysteine.
• Acetaminophen: Methionine appears to reduce the harmful effects of acetaminophen, particularly on the liver—co-administer in the same dose.
• Levodopa (L-dopa): Lower dosages of methionine can help those with Parkinson's disease, but greater levels may interfere with the drug's action. Taking folic acid, vitamin B12, and vitamin B6 together is critical. Monitor for any such medication interactions.

The common side of Methionine includes the following:

• Nausea
• Diarrhoea
• Headaches
• Dizziness
• Abdominal pain.
• Vomiting
• Bloating, gas
• Drowsiness
• Irritability
• Disorientation (alteration of mental status)
• Fever
• Decreased blood pressure

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

• Pregnancy:

There is no sufficient scientific evidence traceable regarding the use and safety of Methionine for use in special populations.

• Paediatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of Methionine for use in special populations.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of Methionine for use in special populations.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of Methionine for use in special populations.

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 the overdosage of methionine. Overconsumption of methionine may lead to hypermethioninemia which may show symptoms that might include gastrointestinal discomfort, nausea, vomiting and elevated levels of homocysteine in the blood.

There is no specific antidote or treatment for excessive intake of supplemental methionine. Methionine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after methionine supplement use or dietary intake. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry Profile of Methionine

Methionine is required for the synthesis of proteins and a variety of biological processes; it is composed of a central carbon attached to an amino group, a carboxyl group, and a side chain that contains sulphur.

For optimal growth and tissue healing, as well as acting as a protein building block. S-adenosylmethionine (SAM), a methyl donor necessary for DNA and RNA methylation and the production of neurotransmitters, is a precursor to methionine. Methionine is then converted to cysteine via the transsulfuration route, which is required to produce glutathione, a vital component of the antioxidant defence system. A raised homocysteine level is associated with cardiovascular hazards and might result from consuming too much methionine. Feedback processes including methionine adenosyltransferase and methionine synthase closely regulate methionine metabolism.

Thus, methionine plays a role in methylation processes, an essential biochemical procedure that alters molecules including DNA, RNA, proteins, and others. This process regulates metabolic, cellular signalling, and gene expression.

Kinetic profile:

• Absorption: Methionine is absorbed from the small intestine via active transport processes. It enters the bloodstream and is used throughout a number of metabolic activities.
• Distribution: Methionine circulates throughout the body and plays essential roles in protein synthesis, cellular functioning, and metabolic pathways. It serves as a precursor for compounds such as S-adenosylmethionine (SAM), which is involved in methylation events vital to gene expression and metabolism.
• Metabolism: Methionine metabolism occurs in two main pathways. It can be transformed into S-adenosylmethionine (SAM), a methyl donor for various processes.
• Elimination: Methionine is not eliminated directly but is involved in complex metabolic processes. Homocysteine, a byproduct of methionine metabolism, is predominantly eliminated in the urine.