What is Methionine?
Methionine is the sulphur containing α-amino acid and is an essential amino acid as the body cannot synthesise it and needs to be obtained from the diet. Methionine converts to cysteine which is another sulphur containing amino acid.
Mehtionine is also the precursor for sulphur based amino acid cysteine which helps with the production of antioxidant glutathionine.
Methionine’s three major metabolic roles are as methyl and sulfur donor and a precursor to other sulfur amino acids such as cysteine and taurine.
Health Benefits of Methionine
Heavy metal detoxification
Methionine may help with heavy metal detoxification, heavy metal toxicity are known to cause health problems and is increasing at an alarmingly rapid rate in the environment and also contaminating food grown at a greater level.
Methionine reduces copper which may be good for copper toxicity but not when copper is already deficient. Mercury reduces methionine, increasing methionine can significantly reduce mercury levels.
Balance urine pH and reduce UTI symptoms
Methionine can help balance urine pH and reduce urinary tract infections (UTIs). Methionine can make urine more acidic which may help prevent urinary tract infections. Methionine can inhibit the growth of various bacteria such as E. coli which is implicated in cystitis and UTIs . Methionine in these cases can be effective due to its acidifying effects on urine creating an inhospitable environment where harmful bacteria do not have a chance to survive.
Some studies have shown that L-methionine can prevent UTIs and recurrent UTIs [R]. UTIs have been shown to be more common in women than in men which means women, especially young women may have an increased need for methionine.
The acidifying effect of methionine is also beneficial as it can help improve the utilisation and efficacy of certain antibiotics. This effect means it may help reduce cystitis and other urinary tract infections which often need antibiotics to treat.
For example, urine with a pH value of between 4 and 6 can optimise the effects of many antibiotics including ampicillin, and prevent the formation of kidney stones.
Methionine can prevent kidney stones
Some animal studies have shown that methionine can reduce the kidney stone formations, however further research may be needed. [R]
Antioxidant properties
Methionine has antioxidant properties which can support bodily functions because of its role in preventing and eliminating toxic substances such as heavy metals, volatile organic compounds (VOCs), harmful chemicals and free radicals. Methionine helps support clearing out damaging substances preventing destruction of substances and cells within the body.
It may help protect the body from harmful radiation. Some studies have shown that methionine may be used in the treatment of acetaminophen poisoning however administration of methionine is time critical and must be given within 10 hours of ingestion to be effective and potentially prevent liver damage. [R]
This amino acid is a precursor of cysteine and taurine.
Methionine is needed for the methylation and sulfation pathways.
Methionine might be needed more during luteal phase which seems to be connected with detoxification and the eradication of hormones and substances the body does not need and especially involved in ridding the body of harmful substances such as heavy metals and toxic chemicals. An example is VOCs from paint fumes and perfumes.
It may be better for women to take methionine during the second part of the luteal phase involved in liver clearance of estrogen as it will help support liver health.
Helps breakdown histamine – a natural antihistamine
Methionine can act as a natural antihistamine as it has shown to reduce histamine levels in the blood. It reduces histamine by helping to break it down. Methionine methylates histamine and deactivates it. This may be useful in cases where allergy or excess histamine production is present.
Methionine is needed for the production of various substances for different functions in the body. Methionine plays a role in the acid-base balance. It provides sulphur atoms for several different chemical processes which help with detoxifying heavy metals and toxic chemicals body may have been exposed to.
Needed for hormones and neurotransmitter synthesis
Methionine plays a role in many functions within the body as well as metabolic processes in the brain. Methionine plays a role in hormones and neurotransmitter synthesis.
Methionine has been used for Parkinson’s disease and depression both of which are connected to an imbalance of neurotransmitters. Methionine has shown to be involved in the production of serotonin and may help synthesise dopamine as it works with phenylalanine which is an amino acid needed for dopamine production.
Methionine supplementation can help restore chemical imbalances caused by a deficiency. Studies have shown that supplementation with methionine reduced trembling or tremors, improved mood and sleep problems and has been used to treat neurological conditions such as Parkinson’s and may be beneficial for other neurological conditions. [R]
Methionine is also a building block for the neurotransmitter adrenaline and therefore plays an important role in the catecholamines pathway. Adrenaline is an excitatory neurotransmitter produced when stressed or excited. It activates fight or flight mode within the body characterized by increased heart rate, blood flow and bood pressure and releasing a boost of energy.
Mehtionine is also needed for certain proteins and hormones which includes carnitine and melatonin.
Carnitine is needed for energy metabolism of the body and is involved in the transport of long-chain fatty acids through the mitochondrial membrane.
Melatonin is a sleep hormone and is needed for deep restful sleep.
Methionine also works synergistically with choline with studies showing a deficiency of both nutrients to impair health functions. Choline is needed for the synthesis of acetylcholine which acts as both an excitatory and inhibitory neurotransmitter acetylcholine. Acetylcholine plays a crucial role in regulating the transmission of nerve impulses to the heart, as well as coordinating the communication between nerves and muscles. [R] [R]
Needed for methylation
Methionine is used in the methylation system and is a process that is achieved by enzymes. Methylation processes heavy metals which helps to detox liver. It has several epigenetic mechanisms which also involves DNA methylation, a mechanism which is important for normal development. The process of methylation has the ability to regulate gene expression, protein function, and RNA processing.
S-adenosylmethionine (SAM) which is the major methyl donor in the cell is produced from methionine by methionine adenosyltransferase (MAT) enzyme. Methionine, betaine, choline, and 5-methyltetrahydrofolate (5-MTHF) are crucial nutrients that provide labile methyl groups in mammalian cells. [R]
Promotes healthy hair growth
Methionine may help reduce hair loss due to its sulphur content. Methionine supports keratin production which is a protein that forms the tissue of skin (outer layer), nails as well as hair.
Adequate methionine helps protect the hair from free radicals. Some studies have shown that methionine may also slow down greying hair in the early stages.
Taking vitamin C will also help protect the body from free radicals.
Agonist / Synergist
Vitamins B6 B9 B12 Amino acids Phenylalanine, Cysteine, TaurineSAMe (S-Adenosyl-l-methionine or S−Adenosyl Methionine) is synthesized from the amino acid methionine by methionine adenosyltransferase (MAT) enzyme
SAMe which needs cofactors methionine, vitamins B9 and B12 for synthesis
Methionine is a precursor of cysteine and taurine
Methionine and cysteine are sulphur containing amino acids
Methionine converts to homocysteine, which then donates a sulphur group to serine (a non-essential amino acid) to form cysteine
Coenzyme-forms of cobalamin are needed for the degradation of propionic acid and the re-methylation of homocysteine to methionine
Vitamin B12 is needed for coenzyme-forms of cobalamin
Methionine synthase is a Cobalamin-dependent enzyme needed to convert homocysteine to methionine
Methionine methylates histamine and deactivates it
Methionine Cycle – Pathway and Cofactors
METHIONINE > HOMOCYSTEINE
Methionine is the precursor of homocysteine
Methionine is a sulfur amino acid involved in the metabolic pathways known as methylation and transsulfuration pathways.
Excess intake of methionine and a deficiency of B vitamins can increase blood levels of homocysteine. B vitamins help lower blood levels of homocysteine. Vitamins B9, B6 and B12 help lower blood homocysteine levels.
SAMe (S-Adenosyl Methionine), which serves as a methyl donor for multiple reactions, is produced when methionine is converted and requires vitamins B9 and B12.
The demethylation of SAMe (SAMe loses its methyl group) results in the formation of SAH (S-Adenosyl Homocysteine).
High homocysteine levels damage blood vessels and have been linked to cardiovascular disease, thrombin generation and neurodegeneration. Studies are showing vitamin B6 in addition to vitamin B12 and B9 can help lower homocysteine levels which helps to protect blood vessels and reduce the risk of cardiovascular disease and other health conditions linked to high homocysteine levels such as strokes. [R] [R] [R]
Homocysteine converts to methionine in the methionine cycle with the cofactors vitamin B9, B6 and B12. This helps conserve methionine levels. This process needs the cobalamin-dependent enzyme methionine synthase, a catalyst for the conversion of homocysteine to methionine.
METHIONINE > HOMOCYSTEINE > CYSTEINE Continuing in this pathway methionine converts to homocysteine, which then donates a sulphur group to serine (non-essential amino acid) and goes on to form cysteine. Cysteine is a non-essential amino acid as it can be synthesised by methionine. Cysteine synthesis needs the enzyme serine acetyltransferase, which is manufactured by the gene cysE. Serine acetyltransferase first converts serine into O-acetylserine. Then O-acetylserine sulfhydrylase enzyme which is manufactured by gene cysK, converts O-acetylserine into cysteine. Methionine to cysteine conversion is irreversible which means cysteine cannot convert back homocysteine or methionine. Cysteine is a precursor of the antioxidant glutathione and needs the enzyme cysteine dioxygenase (CDO)
The amount of cysteine produced depends on the amount of methionine available. Cysteine needs half of the methionine amount required in the diet. CYSTEINE > GLUTATHIONE Cysteine converts to glutathione in the methionine pathway cycle. Glutathione is an important antioxidant produced by the liver. It is made from cysteine, glycine and glutamate / glutamic acid. An adequate supply of these amino acids is needed for the production of glutathione. METHIONINE > HOMOCYSTEINE > CYSTEINE > TAURINE Cysteine is a precursor for taurine and needs the enzyme cysteine dioxygenase (CDO) and cysteine sulfinic acid decarboxylase (CSAD) for synthesis. Taurine is the most abundant free amino acid in the body and not considered essential as it is synthesised from cysteine.
[R] There is some evidence to suggest that methionine metabolism may indirectly affect acetylcholine production. Methionine is involved in the biosynthesis of S-adenosylmethionine (SAMe), which is a key methyl donor in many biological reactions, including the methylation of neurotransmitters such as acetylcholine. SAMe-dependent methylation reactions are important in regulating gene expression, neurotransmitter synthesis, and other cellular processes. Therefore, changes in methionine availability and metabolism could potentially affect SAMe and acetylcholine levels, although this would likely be an indirect and complex relationship. However, more research is needed to fully understand the relationship between methionine and acetylcholine production. Minerals: Cu Metals: Mercury Other: Toxins (chemical, environmental toxins and pollution) Methionine reduces copper which may be good for copper toxicity but not when copper is already deficient Mercury reduces methionine, increasing methionine can significantly reduce mercury levels Chemical and excess toxins will quickly use up methionine as it supports the detoxification pathway Methionine can be found in many protein based food which also includes plant based proteins. The bioavailability of plant based methionine and animal foods are similar. Animal based methionine can be found in meat and poultry such as beef, chicken, liver, ham, and pork in fish such as sardines and salmon, and in dairy products such as egg, cottage cheese, milk, and yoghurt. Grass fed meat are healthier options for nutrients as they are allowed to graze on grass for optimal nutrition. Organic is also important as the meat should be free of pesticides. Plant based methionine include soy, soya bean, brown rice, brazil nuts, sesame seeds, brussel sprouts, cabbage, cauliflower, chives, garlic, watercress, broccoli, oranges, spinach apples and pineapple. Despite the availability of amino acids in a variety of food it may not be enough or sufficient when having any deficiencies and supplementation may be required. Amino acids are mostly soluble and should not be soaked or boiled for prolonged times. High heat cooking may also damage the structure of amino acids. Adults need around 13 to 19 mg of methionine per kg of body weight per day from dietary intake for optimal functioning. Children need more amino acids that adults as their body is still developing. The recommended daily amount for children over the age of three increases by 10% to 20% more than what is needed by adults. For infants the amount required increases by 150% more than what is needed by adults. The requirements may change on individual basis and highly dependent on existing health.
[https://www.ncbi.nlm.nih.gov/books/NBK234922/] Most methionine supplements are suitable for vegans or vegetarians and are indicated on supplement packaging. Methionine is available as a single amino acid or in combination amino acid supplements. It can also be found in some multivitamin supplements and food supplements. Methionine can be found in tablet, capsule, powder and liquid form. Taking single amino acid supplements are not always recommended and may be harmful for those with damaged liver or kidneys. recommended to consult with a healthcare professional for personalized advice on safe methionine intake. Signs and symptoms of methionine deficiency include: *A deficiency of methionine may cause fluid to build up leading to edema as this amino acid is needed to help eliminate various toxins through urine. Methionine can help detoxify the body of heavy metals as it supports metal chelation and processing toxic chemicals for clearance from the body through the liver. Some occupations place workers in hazardous conditions where they are exposed to harmful chemicals. An example includes painters exposed to VOCs released through paint fumes and another example includes cleaners exposed to harmful chemicals through toxic cleaning products. People who are exposed to these chemicals may have an increased requirement for methionine to neutralise these chemicals. Methionine deficiency and low levels in the adrenals is linked to the following health conditions: Stress can impair adrenal function and also deplete methionine. Methionine also has some control over the adrenal glands. Causes of methionine deficiency include: Too much stress (causes excess cortisone production in adrenals). Methionine is required for the regulation of the adrenal-pituitary-hypophyseal axis. It is possible that a combination of low dietary intake and a high methionine requirement could lead to adrenal damage and reduced neurotransmitter production. Modern day farming of cattle and fish may have compromised amino acid quality and content in meat and animal based products reducing methionine content significantly. Along with excess pollution and toxic chemical exposure this may mean supplementation is required especially when detoxing. Some people who have excess chemical exposure may do better with methionine supplementation than obtaining through dietary intake. 500mg – 1g of supplemental methionine may improve the symptoms associated with toxic chemical and heavy metals in the body. Methionine supplements can help meet requirements especially if methionine food intake is low or following a vegan or vegetarian diet. Methionine deficiency means a lower production of homocysteine which is needed to convert to cysteine. Although homocysteine is harmful when high it is needed by the body in sufficient amounts. In a mild deficiency, dietary intake of methionine should be able to resolve this, however in the case of severe deficiency nutritional supplementation may be needed to meet the increased requirements. A urine test can reveal methionine levels to check for deficiency or if levels are adequate. Whilst methionine supplementation can help meet requirements caution is advised as it can cause excessive production of homocysteine levels if certain nutrients are deficient. It is essential to seek medical advice with any existing health conditions before supplementing with methionine. Blood histamine levels are correlated with methylation. The methylation process is affected by histamine levels, when histamine increases methylation decreases and when histamine decreases methylation increases. Low blood histamine may indicate the person is overmethylated and high histamine levels may mean the person is undermethylated. In each case the methylation process may need to be corrected with supplementation. The supplements that support methylation or help lower methylation will also impact the histamine levels accordingly. There is no evidence that genetic methylation defects can be reversed and supplementation may be required to normalize overmethylation or undermethylation conditions. Undermethylation is linked to histadelia (high histamine levels) where a nutritional imbalance of methionine exists. Methionine supplementation may be beneficial for undermethylators. Some symptoms of undermethylation are the same as high histamine levels. Undermethylators tend to have low vitamin B6, magnesium, calcium and methionine with high levels of folate. There is also some family history of undermethylation. Undermethylators tend to have high histamine along with low serotonin, dopamine and norepinephrine. Some practitioners may use a combination of blood tests and other assessments to evaluate histamine levels and methylation status. One approach is to measure levels of histamine and other methyl-related compounds in the blood, such as SAMe, S-adenosylhomocysteine (SAH), and methionine. Elevated histamine levels and low SAMe levels may suggest an imbalance in methylation processes and potential undermethylation.
Another approach is to evaluate symptoms associated with histamine imbalance, such as anxiety, depression, allergies, and gastrointestinal issues. If these symptoms are present and other potential causes have been ruled out, it may suggest a histamine imbalance related to undermethylation. Laboratory tests for total blood histamine for undermethylators will be above 70ng/ml and show direct absolute basophils and low ceruloplasmin levels. Nutrients that may help undermethylators include calcium, magnesium, zinc, methionine, TMG, omega-3 oils, vitamin B6, vitamin A, vitamin C, vitamin E, SAMe and vitamin B8 (inositol). Nutrients that may be harmful especially in supplemental doses for undermethylators include vitamin B9 (Folate), choline, DMAE, copper and histidine. Methionine is another amino acid that may reduce symptoms of allergies and allergy related conditions such as asthma by helping to break down and eliminate high histamine. Methionine methylates histamine and deactivates it. Methionine helps with histamine breakdown (histamine is involved in allergies and asthma) Methionine methylates and deactivates histamine through its role in the methylation cycle and synthesis of active nutrient SAM-e Undermethylators tend to have low vitamin B6, magnesium, calcium and methionine with high levels of folate. There is also some family history of undermethylation. Studies suggest that vitamin B-6 may serve as a coenzyme catalyst in methylation processes within the central nervous system, potentially impacting cognitive function and mood. Methyl groups are needed to process histamine. Supporting the methylation cycle, such as the production of SAM-e will help breakdown and lower histamine levels. Methionine is needed for the methylation cycle and also helps with the synthesis of SAM-e. Methylation may be dependent on a woman’s monthly cycle and correlate with hormones and their synergistic neurotransmitter counterparts throughout the cycle. For example histamine rises alongside estrogen production which occurs in the follicular phase. In this phase serotonin and dopamine also rises as these key neurotransmitters rise alongside estrogen. So it may be beneficial to not methylate in the follicular phase to increase necessary levels of histamine. In the luteal phase especially in the last fourth week prior to menstruation estrogen is cleared out via the liver, histamine levels also drop or at least it should drop along with the drop in estrogen which means increasing methylation at this phase is probably more appropriate and supportive of the bodily functions. This is likely to be applicable in healthy individuals and not those who have a predominant issue of overmethlyation or undermethylation. Methionine toxicity is also known as hypermethioninemia. Although methionine is unlikely to cause toxicity when obtained from diet, it can cause toxicity due to high intake usually through excessive high dosed supplementation. Methionine and cysteine are considered to be some of the more toxic amino acids for humans and animals. Symptoms of methionine toxicity include: Methionine is stored in the heart, with excessive amounts causing symptoms such as facial flushing and left sided chest pain / pressure with exercise. [R] Excessively high methionine intake can increase blood levels of homocysteine and deficiency of some nutrients such as vitamin B6, B9 and B12 can increase the likelihood of an increase of homocysteine which may increase risk of heart disease. Methionine should be taken with vitamin B6, B9 and B12 as a deficiency in these nutrients can increase conversion of methionine to homocysteine. People with high homocysteine levels should avoid methionine supplements which includes those with the inherited disease homocystinuria type I. Although homocysteine is a natural and necessary component for health high levels can be detrimental and dangerous and can lead to cardiac related health problems. Homocysteine is known for its high reactivity. Causes of high methionine levels include: High methionine levels is common in liver disease. An early maturation of liver enzymes can result in a pattern of methionine and tyrosine. Methionine and tyrosine have shown to be high in hereditary and acquired liver disorders. [https://pubmed.ncbi.nlm.nih.gov/23769068/] Methionine is the most toxic of all amino acids at very high doses [R] Methionine is metabolized into sulfuric acid, which can be beneficial as the kidneys use this amino acid to increase the acidity of urine. This may have therapeutic benefits in the treatment of urinary tract infections (UTIs) and cystitis. Methionine is an essential amino acid that is required for proper growth and development, but excessive intake of methionine can have negative health effects. There is no established safe upper limit for methionine intake, but the recommended daily intake (RDI) of methionine for adults is around 19 mg/kg of body weight. Consuming more than this amount could potentially lead to increased production of homocysteine, which is a risk factor for cardiovascular disease. Additionally, high levels of dietary methionine have been associated with increased risk of cancer and liver damage in animal studies. Some studies have shown that a methionine restricted diet and nutritional plan can inhibit cancer cell growth which may work well as an adjunct to chemotherapy. Some studies have shown that glutathione synthesis, polyamine synthesis and methyl group donor have some effect on how methionine restriction can effect cancer and be used as a potential treatment along with nutrition for cancer patients
[R] People with sulphur allergies may not be able to tolerate methionine especially from supplementation as it is a sulphur based amino acid. Glycine has also been shown to promote weight loss through its ability to mitigate methionine toxicity. In addition to this methionine restriction has shown to extend lifespan of rodents though how this is done is not fully known. [R] Overmethylation is linked to histapenia (low histamine levels) where a nutritional imbalance of methionine exists. Overmethylators tend to have low histamine along with high serotonin, dopamine and norepinephrine. Laboratory tests for total blood histamine for overmethylators will be below 40 ng/ml, along with low levels of direct absolute basophils and high serum copper levels. Methionine supplementation may be harmful for overmethylators. Supplements or nutrients from food source that may be useful and benefit overmethylators include B3, B12, B9, choline, C, E, DMAE, manganese, zinc and omega-3 oils. Nutrients that may be harmful especially in supplemental doses for overmethylators include methionine, tryptophan, phenylalanine, tyrosine, SAMe, inositol, St. John’s Wort, copper, TMG and DMG.Antagonists
Food Sources of Methionine
Recommended Daily Allowance
Methionine Supplementation
Deficiency Symptoms of Methionine
Toxicity Symptoms of Methionine