Methionine

Methionine is an essential sulphur-containing amino acid that provides the body with sulphur and methyl groups. In addition to being a building block for proteins, methionine has several unique properties. One of these is its ability to be converted into important sulfur-containing molecules (1). Sulfur-containing molecules have a variety of functions that include protecting body tissues, modifying DNA and maintaining cell function (2). These important molecules must be made from sulfur-containing amino acids, and of the amino acids used in the body to make proteins, only methionine and cysteine contain sulfur.

Even if the body can produce the amino acid cysteine itself, methionine must be supplied through food. In addition to this, methionine plays a crucial role in starting the process of making new proteins in cells - a process that occurs continuously as cells age and protein is broken down. This amino acid also starts the process of producing new proteins in the muscles after training sessions that damage the muscles (3). Methionine is also involved in the production of cysteine - the other sulphur-containing amino acid needed to make proteins in the body. Cysteine, in turn, can be converted into a number of other molecules including proteins, glutathione and taurine. Glutathione is also known as the "master antioxidant" due to its role in the body's defense response. It also plays a role in the metabolism of nutrients and the production of DNA and proteins. Taurine has many functions that help maintain the health and proper function of cells. The metabolically active form of methionine is S-adenosyl-methionine (SAM), which is found in virtually all body tissues and fluids. It is required for the synthesis, stimulation and breakdown of many substances in the body. It also contributes to the formation of adrenaline, carnitine, choline, creatine, melatonin and nucleic acids. All in all, methionine is directly or indirectly involved in many important processes in the body due to the molecules into which it can be converted.

Methionine plays a role in the methylation of DNA

DNA contains the information that makes a person who they are. Although much of this information remains the same throughout life, environmental factors can alter some aspects of DNA. This is one of the most interesting roles of methionine - it can be converted into the aforementioned molecule called SAM, which can alter DNA by adding a methyl group to it. The amount of methionine in the diet could influence the extent to which this process takes place, although many questions remain unanswered. It is possible that increasing the amount of methionine in the diet can either increase or decrease the amount of DNA modification by SAM. In addition, these changes may have positive effects in some cases and negative effects in others. For example, research has shown that a diet richer in nutrients that add methyl groups to DNA may reduce the risk of colorectal cancer (4).

However, other research has shown that higher methionine consumption could exacerbate conditions such as schizophrenia, perhaps due to methylation of DNA (5).

The methionine confusion

Some people assume that methionine is something that needs to be reduced in the diet to maintain optimal health. But as with most other things in biology, methionine is neither good nor bad. We know that methionine is an essential amino acid, which means that certain amounts must be supplied in the diet to maintain good health. On the other hand, some people read some scary things on the internet about this amino acid, ranging from an increased risk of heart disease to brain damage. However, methionine is considered safe and harmless in the amounts it is found in food. A serious risk only exists at extremely high levels (6).

Restriction science

Studies carried out on animals suggest that restricting methionine consumption can extend lifespan, although this has not yet been confirmed in humans (7). A 2005 study showed that methionine restriction without calorie restriction extended the lifespan of mice (8). Several studies have found that methionine restriction in mice can also inhibit certain disease processes associated with ageing (9). However, there are no human studies that have investigated the effects of methionine on age-related pathways and diseases in humans. In rats, dietary methionine increases mitochondrial production of reactive oxygen species and oxidative damage to DNA and liver. Scientists hypothesize that this is a plausible mechanism for liver toxicity from excessive methionine intake, although human data confirming this is lacking (10).

Methionine has important functions in the body

In the body, methionine helps to prevent excessive fat deposits in the liver. It also supports the regeneration of the liver and kidneys. Methionine has a uric acidifying effect. It has an antioxidant effect and can detoxify or accelerate the breakdown of heavy metals such as lead, histamine and ammonia. As a precursor of glutathione, methionine may also protect against radiation damage. It is also required for the metabolism of selenium. Methionine or SAM is also particularly active in the brain and has antidepressant effects.

The main sources of methionine

Methionine is found in many foods. It is abundant in fish, meat and vegetables (e.g. broccoli, green peas, Brussels sprouts, spinach), eggs, wholemeal bread and rice.

Some foods rich in methionine and cysteine* contain the following per 100 grams

Methionine/cysteine

Salmon 700 mg
Prawns 670 mg
Turkey, breast meat 630 mg
Chicken, breast meat 620 mg
Soybeans 580 mg
Beef, fillet 570 mg
Cashew nuts 380 mg
Wheat germ 280 mg
Emmental cheese 250 mg

* Methionine is the precursor of cysteine, the latter is difficult to determine in food. The content of these two sulphur-containing amino acids is therefore usually stated together.

Typical groups for an additional requirement of methionine

Exposure to heavy metals
for allergies
for depression
for wound healing and muscle injuries
for urinary tract infections
for liver inflammation (due to drug or alcohol abuse)
Parkinson's disease (taking L-dopa)

Methionine contributes to many bodily functions through its active involvement in the formation of hormones, neurotransmitters and nucleic acids. It can influence a number of diseases. For example, methionine can reduce histamine and thus improve allergies. Methionine can also protect against urinary tract infections. Bacteria that can cause such infections are inhibited in their growth by methionine. It also prevents phosphate stones from forming in the urinary tract as a result of chronic urinary tract infections. As methionine in its active form SAM is particularly active in the brain, depressive moods can be positively influenced. The administration of the drug L-Dopa in Parkinson's disease reduces SAM levels in the brain. Additional doses of methionine can then improve mobility and activity, and can also improve tremors, sleep and moods.

Possible health benefits of methionine

Methionine may support joint health

Sulphur compounds are important for the synthesis of glycosaminoglycan, which is important for cartilage.

One study concluded that a large proportion of the population - particularly older people - probably do not consume enough sulphur (11).

Incidentally, supplementation with methionine/cysteine is used in animal breeding to increase growth (12)

Methionine could have a positive effect on inflammatory diseases

Scientists suspect that the need for sulphur-containing amino acids such as methionine increases in inflammatory diseases and oxidative stress. They hypothesize that this is at least partly due to the increased glutathione requirement and increased sulfur excretion (13). In experiments with pigs, stimulation of the immune system led to increased methionine utilization (14). Observations in animals indicate that the oxidative defense is depleted during infections and after injuries. In studies with mice infected with the influenza virus, a 45% decrease in blood glutathione levels was observed (15).

According to some human studies, glutathione levels can fall in the following cases:

Asymptomatic HIV infections
Abdominal surgery
Hepatitis C
Ulcerative colitis
cancer
Cirrhosis
sepsis

However, no human studies have yet been conducted to investigate whether methionine supplementation can be helpful in these cases. It is also not yet known whether higher dietary methionine intake can play a role in preventing inflammatory diseases and other conditions associated with low glutathione levels.

Low methionine levels could promote venous thrombosis

In a case study of nearly 700 people, low methionine levels were associated with a risk of recurrent venous thrombosis, although the impact of methionine supplementation on venous health is not yet known (16).

Methionine could have a positive effect on liver health

Sulfation is the primary pathway for detoxification of pharmacologic agents by the liver. Thus, oral methionine supplementation may help in the treatment of acetaminophen poisoning. Methionine is used to prevent liver damage caused by acetaminophen poisoning. For example, taking 2.5 grams of methionine every four hours for a total of four hours prevented liver damage and death after acetaminophen poisoning (17).

In addition, methionine can reduce excessive fat accumulation in the liver by acting as a lipotrophic agent that promotes the breakdown of fat. It can also reduce cholesterol levels by increasing lecithin production by the liver (18). The liver-protective effects of methionine could also be due to a possible increase in glutathione production caused by methionine. Glutathione is the body's most powerful antioxidant that can protect the liver from damage. In addition to this, methionine itself also appears to have antioxidant properties. SAMe, to which methionine is converted in the body, can also influence various pathophysiological processes in the liver including oxidative status, liver cell death and malignant changes. SAMe synthesis decreases in chronic liver disease and scientific research suggests that SAMe supplementation (or increased production) may be helpful in liver injury and may counteract exacerbation of liver injury (19). A recent study review also suggests that SAMe can be used as the basis of drug treatment to improve liver function (20). Interestingly, however, caution is advised when using methionine in patients with severe liver damage, as it can exacerbate hepatic encephalopathy (a loss of brain function when the liver can no longer remove toxins from the blood) (21).

Methionine supports glutathione production

Cysteine and methionine are not stored in the body. Sulphur helps the body to produce glutathione, which is essential for the body's antioxidant protection (22). Some scientists suggest that a deficiency of sulfur-containing amino acids such as methionine can reduce gluthation levels. Studies suggest that a dietary excess of methionine is oxidized to sulfate, which is excreted in the urine or stored in the form of glutathione (23). According to limited studies, glutathione levels are reduced in a number of diseases and with certain medications. However, whether methionine supplementation can help to influence this imbalance is unknown (22). One hypothesis is that methionine and sulfur may be able to reduce losses of glutathione associated with nutritional deficiencies and increased utilization due to disease or altered immune function (22). In animals, it has been observed that when methionine levels are low, the synthesis of sulfate and glutathione is reduced. Scientists believe that this may impair immune system function and antioxidant defense mechanisms, although human studies are still lacking (22).

Methionine could counteract graying of the hair

A loss of methionine has been associated with graying of the hair with age. Scientists hypothesize that this deficiency leads to an accumulation of hydrogen peroxide in the hair follicles and a gradual loss of hair color (23).

Methionine could support digestive tract health

Methionine is often found in the same foods as cysteine. Limited research suggests that dietary methionine (and cysteine) may be important in maintaining gut and immune health during development and inflammatory diseases (25). For example, it was observed that piglets receiving cysteine and methionine supplementation (25 mg per kilogram of body weight each) had less oxidative stress in the gut than piglets fed a normal diet. They also had a higher intestinal villus weight and a greater number of goblet cells (25).

Scientists believe that the following pathways are partly responsible for the effects of methionine on the digestive tract:

A transformation to glutathione, taurine and cysteine
A reduction of oxidative stress in the digestive tract
An influence on structures of the digestive tract such as intestinal villi and goblet cells

Methionine could support the immune response

Scientific research suggests that methionine may be important for immune system function and methylation (26, 27).

Cell studies have investigated the influence of methionine on the immune system and an increase in the levels of glutathione and taurine, as well as the number of CD4+ and CD8+ cells (13).

Methionine could promote fertility

In animals, it has been observed that low methionine levels reduce fertility (28). However, this has not yet been studied in humans.

Methionine could help with lupus

According to two small studies, methionine and other methyl donors - including cysteine, choline and cofactors such as vitamin B6 - were reduced in lupus patients (29). In addition, it has been shown that reducing the levels of methionine and choline in the diet worsened the severity of lupus in mice (30). However, there are still no clinical studies that have investigated the efficacy and safety of methionine supplementation in lupus patients.

When methionine is deficient in the body

A lack of methionine can lead to metabolic disorders. These include fatty degeneration of the liver, for example, but also skin and hair growth disorders. A deficiency can also lead to increased tiredness or lethargy. Low methionine levels can also lead to depressive moods and, in severe cases, psychiatric disorders.

Recommended intake

The recommended daily intake of methionine plus cysteine is 19 mg per kilogram of body weight per day, which corresponds to around 1.3 grams for a person weighing 68 kilograms (31). However, some scientists recommend twice this amount based on the limitations of the studies used to determine the recommended daily intake (12). Older people often have low methionine intakes and studies have shown that they may need a higher intake in the range of 2 to 3 grams (32). Despite the fact that certain groups may benefit from increasing their methionine intake, many people's diets already exceed 2 grams of methionine plus cysteine per day. A number of different diets including vegan, vegetarian and traditional high-protein diets are estimated to contain between 2.3 and 6.8 grams of these amino acids (12).

Safety and side effects

Methionine appears to be safe and harmless for the treatment of acetaminophen poisoning when used under medical supervision. One should not self-medicate with methionine. Self-medication with methionine may not be safe and harmless if larger amounts are used than those normally found in food. Too much methionine can cause brain damage and death. Methionine may also promote the growth of certain tumors. Doses of up to 2 grams of methionine daily over a long period of time have not shown any serious side effects. Doses of up to 8 grams per day are generally considered to have no side effects. However, methionine is considered to be the most toxic amino acid. If the intake is too high, homocysteine is increasingly formed as an intermediate product due to the breakdown of methionine. This is considered an independent risk factor for heart disease and strokes. The formation of homocysteine can be reduced by taking vitamin B6 at the same time. B6 helps to convert homocysteine more quickly into cysteine or back into methionine. High doses of methionine can also increase the excretion of calcium in the urine. Attention should be paid to this in the case of osteoporosis and an existing risk of osteoporosis. Methionine can lower blood pH, so gout patients should only take it under medical supervision.

Precautions and warnings

Pregnancy and lactation: Not enough is known about the safety of methionine during pregnancy and lactation. For this reason, pregnant and breastfeeding women should avoid methionine to be on the safe side.

Acidosis: Methionine can cause changes in blood pH and should not be used by people suffering from acidosis.

Arteriosclerosis: There are concerns that methionine may aggravate existing arteriosclerosis. Methionine can increase homocysteine levels, especially in people who do not have enough folate, vitamin B12 or vitamin B6 in their bodies, or in people whose bodies have problems processing homocysteine. Too much homocysteine is associated with an increased risk of heart and blood vessel disease. Liver disease including cirrhosis: Methionine may exacerbate liver disease. Methylenetetrahydrofolate reductase (MTHFR) deficiency: This is a hereditary disorder that alters the way the body processes homocysteine. People who suffer from this disorder should not take methionine supplements, as methionine can lead to an increase in homocysteine levels in these people. Too much homocysteine could increase the risk of developing diseases of the heart or blood vessels. Schizophrenia: High doses of methionine (e.g. 20 grams per day for 5 days) may cause confusion, disorientation, delirium, agitation, listlessness and other similar symptoms in people suffering from schizophrenia.