S-adenosyl-methionine SAMe

Methionine Cycle The Methionine Cycle takes the amino acid methionine, uses the MAT gene to make SAMe. SAMe is the methyl donor that gives a methyl group where it is needed for well over 100 functions. The GAMT gene takes SAMe to make creatine. After donating a methyl group and making creatine, SAMe turns into SAH and then the AHCY gene turns it into homocysteine.

Variants in MTRR, MTR, BHMT, PEMT will slow the conversion of homocystine into methionine.

S-adenosyl-methionine:

Some of the important reactions in which SAM is involved are:

Methylation of DNA and RNA. DNA- and RNA-methylases use SAM as a source of methyl groups.
A major target of methylases is the 5 position of cytosine in DNA. The degree of methylation correlates with transcriptional activity. Globin genes, for example, are highly methylated in non-erythroid cells but not in erythroid cells.
The conversion of epinephrine to norepinephrine is also catalyzed by an N-methyl transferase that uses SAM. Note that because methionine is an essential amino acid, if it is limiting, choline could also become a nutritional requirement.
S-Adenosylmethionine, the methyl group donor for many biosynthetic processes, also participates directly in spermine and spermidine biosynthesis. S-Adenosylmethionine, the principal source of methyl groups in the body, also contributes its carbon skeleton for the biosynthesis of the 3-diaminopropane portions of the polyamines spermine and spermidine
Important pathways requiring SAM include synthesis of epinephrine and of the 7-methylguanine cap on eukaryotic mRNA. After donating the methyl group, SAM is converted to homocysteine and remethylated in a reaction catalyzed by N-methyl THF-homocysteine methyltransferase requiring both vitamin B12 and N-methyl-THE. The methionine produced is once again used to make SAM. SAMe is one if not the most powerful methyl donors. It is a substrate that is used in Trans Methylation reactions of which there are hundreds. After SAMe gives away its methyl group it becomes SAH [S-adenosylhomocysteine]. As SAH builds up it blocks many of the MethylTransferase enzymes and then they cannot work properly. It may be that one of the MethylTransferase enzymes is being blocked by too much SAH and this is the cause of your fatigue.

Methionine:

Methionine is only one of two amino acids that provide sulfur for the body, which is required to sulfate many compounds. A sulfur-containing essential L-amino acid that is important for many body functions.
Required for normal growth and development of humans, other mammals, and avian species.
Methionine is an alpha-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3, classified as nonpolar.
There is scientific evidence that restricting methionine consumption can increase lifespans in some animals. A 2005 study showed methionine restriction without calorie restriction extends mouse lifespan.
Several studies showed that methionine restriction also inhibits aging-related disease processes in mice and inhibits colon cancer in rats.
In rats, methionine supplementation in the diet specifically increases mitochondrial ROS production and mitochondrial DNA oxidative damage in rat liver mitochondria offering a plausible mechanism for its liver toxicity.
Since methionine is an essential amino acid, it cannot be entirely removed from animals’ diets without disease or death occurring over time. For example, rats fed a diet without methionine developed a fatty liver, anemia and lost two-thirds of their body weight over 5 weeks.

Methionine Supplementation:

Methionine (in the form of SAM-e) and Cysteine (in the form of NAC) are commonly taken as supplements.
Methionine converts to cysteine, so supplementing with cysteine reduces the requirements for methionine.

Dietary methionine:

Alone is capable of providing all the necessary body sulfur (except thiamin and biotin).

Methylation:

In addition to being a substrate for protein synthesis, it is an intermediate in transmethylation reactions, serving as the major methyl group donor in vivo, including the methyl groups for DNA and RNA intermediates.
Methionine is a methyl acceptor for 5-methyltetrahydrofolate-homocysteine methyltransferase (methionine synthase), the only reaction that allows for the recycling of this form of folate, and is also a methyl acceptor for the catabolism of betaine.

Health Effects:

Chronically high levels of methionine are associated with at least 7 inborn errors of metabolism including Cystathionine Beta-Synthase Deficiency, Glycine N-methyltransferase Deficiency, Homocystinuria-megaloblastic anemia due to a defect in cobalamin metabolism, Methionine Adenosyltransferase Deficiency, Methylenetetrahydrofolate reductase deficiency and S-Adenosylhomocysteine (SAH) Hydrolase Deficiency.

Route of Exposure:

Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.
The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver leads to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as it's chelating ability.

SAMe:

Has been used for lead overload and thought to work against mercury as well.
When it stimulates CBS it converts homocysteine into glutathione. If a negative reaction occurs after taking methyl cycle supplements, it's most likely a detox reaction. It could also be from increased production of ammonia hydrogen sulfide, sulfite, or sulfate from the generation of homocysteine in an overactive pathway.
One third is used to create creatine which is involved in energy recycling of ATP. Creatine can help reduce the demand for the methyl group and SAMe.

Cysteine:

Methionine is also required for synthesis of cysteine. Methionine is accepted as the metabolic precursor for cysteine. Only the sulfur atom from methionine is transferred to cysteine; the carbon skeleton of cysteine is donated by serine.

Detox:

Sulfation is a major pathway for detoxification of pharmacological agents by the liver. Sulfur helps produce glutathione, which is critical for proper antioxidant function. Tylenol requires sulfate for its excretion and it’s often given in high doses to alleviate pain (4 gm/day, as recommended on the label). This equivalent dosage in rats causes a depletion of sulfate, which can be corrected by methionine supplementation. Tylenol was more toxic and was eliminated more slowly in animals deficient in sulfates.

Glutathione:

Cysteine and methionine are not stored in the body. When you have a deficiency in sulfur amino acids such as methionine, glutathione levels suffer more than more critical processes such as protein synthesis. Any dietary excess is readily oxidized to sulfate, excreted in the urine (or reabsorbed depending on dietary levels) or stored in the form of glutathione (GSH).
Glutathione levels are lower in a large number of diseases and following certain medications, which can be reversed by taking methionine.
Methionine and sulfur should be able to spare losses of Glutathione associated with dietary deficiencies, increased utilization due to disease or altered immune function.
Under conditions of low methionine, synthesis of sulfate and Glutathione will be reduced, which is likely to negatively influence the function of the immune system and of the antioxidant defense mechanisms.

Gut Health:

Methionine is often found in the same foods with cysteine. There is some evidence that dietary methionine (and cysteine) is important to ensure the health of the intestine and immune function during development and in inflammatory states.
Relative to healthy piglets fed a deficient diet, piglets supplemented with cysteine (0.25 g/kg) and methionine (25 g/kg) had less intestinal oxidative stress, improved villus height and area and crypt depth, and a higher number of goblet cells.

Benefits of methionine for gut health:

A precursor for GSH, taurine, and cysteine
Reduces intestinal oxidative stress
Intestinal structure
Increases goblet cells and proliferating crypt cells

Immune System:

For the immune system, methionine increases glutathione, taurine, CD4+ and CD8+ cells.

Methylation:

Methionine is important for methylation (it’s the precursor to SAM).
Many people who don’t methylate well enough would do better with higher intakes of methionine. However, it’s not clear exactly what effects methionine has on methylation.
Methionine supplementation has the potential to induce relevant changes in methylation and expression of genes. It remains to be determined whether high Methionine intakes have a greater tendency to induce DNA hyper- or hypomethylation.
Methionine can be helpful and harmful in different situations and further research is needed to clarify exactly which genes are affected by this.

Joints:

Sulfates/sulfur is critical for glycosaminoglycan synthesis, which is important for cartilage.
One study concludes that a “significant proportion of the population that included disproportionally the aged, may not be receiving sufficient sulfur and that these dietary supplements [glucosamine/chondroitin sulfate], were very likely exhibiting their pharmacological actions by supplying sulfur.
In order to increase growth, chicken diets are always supplemented with methionine/cysteine.

Heart and Cells:

Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids. Improper conversion of methionine can lead to atherosclerosis.

Fertility:

Methionine restriction causes lower fertility.

Inflammatory Conditions:

Under inflammatory conditions and oxidative stress, the requirement for sulfur amino acids such as methionine goes up, in part because of increase glutathione needs and sulfur excretion.
The immune system also uses up methionine when it’s stimulated in pigs.
Observations in experimental animals and patients indicate that antioxidant defenses become depleted during infection and after injury. For example, in mice infected with influenza virus, there was a 45% decrease in the GSH contents of blood.

Epigenetics and Stress:

The offspring of stressed rats have epigenetic changes in methylation of the cortisol receptor (GR), which can cause changes in the HPA axis and negatively affect these offspring.
Methionine infusion into adult rats reverses the negative epigenetic effects on DNA methylation, nerve growth factor-inducible protein-A binding, the cortisol receptor (GR), and hypothalamic-pituitary-adrenal and behavioral responses to stress.

Lupus:

Methionine and other methyl donors including cysteine, choline, and cofactors such as vitamin B6 were significantly reduced in Lupus/SLE patients compared to healthy matched controls. Reducing the methionine and choline content of the diet increased lupus disease severity in genetically susceptible mice.

Greying of Hair:

Loss of methionine has been linked to senile greying of hair. Its deficit leads to a buildup of hydrogen peroxide in hair follicles and a gradual loss of hair color.

Venous Thrombosis:

Low fasting methionine concentrations are a risk factor for recurrent venous thrombosis.

Diet:

High levels of methionine can be found in animal products (eggs, fish, meats) and some nuts and seeds; methionine is also found in grains.
Most fruits, vegetables, and beans are low in methionine.
Compared to fish eaters and meat eaters, vegans have the lowest intake of methionine.

RDA:

The RDA for methionine (combined with cysteine) for adults has been set at 14 mg/Kg of body weight per day. Therefore a person weighing 70 Kg, independent of age or sex, requires the consumption of around 1.1 g of methionine/cysteine per day.
One study by Tuttle et al. found that feeding purified amino acid diets containing variable amounts of methionine to older individuals at the VA Hospital required significantly higher levels of methionine than those previously established by the RDA. They all needed more than 2.1 g/day, with some subjects requiring up to 3.0 g/day to remain in positive nitrogen balance.

The adequacy range of dietary requirements of specific amino acids in disease states is difficult to determine. Requirements may not be similar in disease with regard to protein synthesis.
Requirements for this purpose can be assessed only when such a function can be measured and related to clinical outcome.
There is an apparent consensus concerning normal sulfur amino acid (SAA) requirements. WHO recommendations amount to 13 mg/kg per 24 h in healthy adults. This amount is roughly doubled in artificial nutrition regimens. In disease or after trauma, requirements may be altered for methionine, cysteine, and taurine. Although in specific cases of congenital enzyme deficiency, prematurity, or diminished liver function, hypermethioninemia or hyperhomocysteinemia may occur, SAA supplementation can be considered safe in amounts exceeding 2-3 times the minimum recommended daily intake. Apart from some very specific indications (e.g., acetaminophen poisoning) the usefulness of SAA supplementation is not yet established.
Methionine is known to exacerbate psychopathological symptoms in schizophrenic patients, there is no evidence of similar effects in healthy subjects. The role of methionine as a precursor of homocysteine is the most notable cause for concern. A loading dose of methionine (0.1 g/kg) has been given, and the resultant acute increase in plasma homocysteine has been used as an index of the susceptibility to cardiovascular disease. Although this procedure results in vascular dysfunction, this is acute and unlikely to result in permanent damage. However, a 10-fold larger dose, given mistakenly, resulted in death.
Longer-term studies in adults have indicated no adverse consequences of moderate fluctuations in dietary methionine intake, but intakes higher than 5 times normal resulted in elevated homocysteine levels. These effects of methionine on homocysteine and vascular function are moderated by supplements of vitamins B-6, B-12, C, and folic acid. In infants, methionine intakes of 2 to 5 times normal resulted in impaired growth and extremely high plasma methionine levels, but no adverse long-term consequences were observed.

Average Intake:

Intake of methionine/cysteine measured in 32 individuals ranged between 1.8 and 6.0 g/day (14 and 45 mmol/day). Sulfur amino acids were lower in individuals who tended to be more health conscious and consume no red meat and little animal protein, as well as those consuming “fad diets”.
Many older people could turn out to be outright deficient.

Average sulfur amino acid intake associated with the consumption of a variety of typical diets:

Group SAA (g/day)

I High-protein 6.8

II High-protein low-calorie 5.0

III Oriental-American 4.8

IV Average balanced 4.3

V Fast-food 4.1

VI Dieter 3.5

VII Lacto-ovo-vegetarian 3.0

VIII health-conscious diet 2.6

IX Vegan 2.3

X elderly people (75 yr old) 1.8

High Doses:

A “loading dose” of methionine (0.1 g/kg) has been given, and the resultant acute increase in plasma homocysteine has been used as an index of the susceptibility to cardiovascular disease. A 10-fold larger dose, given mistakenly, resulted in death. Longer-term studies in adults have indicated no adverse consequences of moderate fluctuations in dietary methionine intake, but intakes higher than 5 times normal resulted in elevated homocysteine levels.
Longer-term studies in adults have indicated no adverse consequences of moderate fluctuations in dietary methionine intake, but intakes higher than 5 times normal resulted in elevated homocysteine levels.
In infants, methionine intakes of 2–5 times normal resulted in impaired growth and extremely high plasma methionine levels, but no adverse long-term consequences were observed.

Methionine Restriction:

Methionine restriction has been known for decades in animal longevity research. There are three fallacies that you should be careful about when it comes to drawing conclusions about your optimal methionine level.
If restricting methionine increases maximum lifespan, then restricting it is not necessarily optimally healthy.
If excess methionine is bad, then restricting it doesn’t mean it’s good.
If it works in animals to increase lifespan, it doesn’t mean it’ll work in humans because we have a very different environment and somewhat different biology.
A substance like methionine has what’s called a biphasic response. If you get too little or too much, it’ll cause a lot of problems. You need to get a balanced amount, and that level will be different for everyone.

Longevity:

After reading longevity research for a while, you start to realize that it doesn’t really apply to humans all that much.
The issue with methionine restriction is the amount that you’d have to lower methionine for it be beneficial for longevity is not practical for other purposes.
It’s not that much different than lowering free radicals by not breathing. It’s not practical in the long run because of the side effects.
Methionine is important to the immune system. If you take less methionine over the long run, you may become susceptible to chronic infections and that can cause many problems.
Animals in longevity studies are in sterile environments and if they live longer in a sterile environment, it doesn’t mean they will in the real world.
A lot of things that cause longevity are bad for specific people. Lowering IGF-1 can be good for longevity, but for some people, higher levels are much better for their biology. Same with methionine.

Homocysteine:

Some say that methionine is bad because it raises homocysteine and elevated homocysteine is associated with negative health outcomes and we know the role of methionine as a precursor to homocysteine. The problem is that fluctuations in dietary methionine intake do not alter blood homocysteine concentrations.
To increase homocysteine, a high dose of pure methionine is required. This dose has been estimated to be equivalent to about 5 times the normal daily intake of methionine.
Vegetarians, who have lower methionine intake, actually have higher homocysteine levels because of lower B12. Also, other factors can balance methionine-induced homocysteine in meat eaters (assuming it did raise homocysteine, which it doesn’t). For example, glycine and serine balance the negative effects of high dose methionine on homocysteine.
Glycine, serine, and B12 are rich in an animal food diet, but not in a vegan diet.

Interactions:

A study published in Nature showed adding just the essential amino acid methionine to the diet of fruit flies under dietary restriction, including restriction of essential amino acids, restored fertility without reducing the longer lifespans that are typical of dietary restriction.
This lead the researchers to determine that methionine “acts in combination with one or more other essential amino acids to shorten lifespan”.

High Methionine Diet:

Schizophrenics:

In animals, high levels of methionine are capable of promoting schizophrenia by methylating and stopping the production of the GABRB2 gene, which controls the production of a certain component of the GABA receptor. A lower GABAergic function is a cause of schizophrenia.

B Vitamins:

If you have a high methionine intake, special attention should be paid to folic acid and vitamins B6 and B12 under these circumstances.

Phosphatidylcholine:

In the methyl cycle, one-third of generated SAMe is used to generate Phosphatidylcholine. It takes 3 SAMes to produce one of these.
Increases the demand for SAMe and SAH. The enzyme that uses SAMe to create SAH and generates phosphatidylcholine is inhibited when phosphatidylcholine levels are high. Increasing the supply of SAMe stimulating BHMT Turi methylate homocysteine back into SAMe is good for your brain, liver and blood vessels.
I don’t believe the studies about methionine restriction relate to humans because in the real world people don’t die from too much methionine. Other things go wrong first and not getting enough, however, can be problematic to some people, even if it potentially helps them in another way (assuming that lower levels are somewhat beneficial in some ways).
Methionine may be analogous to IGF-1: it can possibly be good for longevity, but it’ll worsen performance and it could worsen autoimmunity.

High Protein Diet:

Studies have established convincing evidence that not only the total protein intake, but the availability of specific dietary amino acids (in particular glutamine, glutamate, and arginine, and perhaps methionine, cysteine, and threonine) are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.
These amino acids each have unique properties that include, maintaining the integrity, growth, and function of the intestine, as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers, specific T cell functions, and the secretion of IgA by lamina propria cells.
Most do better with a higher protein diet, and this is, in part, because a higher protein diet is needed when people have gut problems. I made the mistake of believing the vegan myths that lower protein is healthier for everyone (it might be for some people).

Methionine & Cysteine:

A precursor for GSH, taurine, and cysteine
Reduces intestinal oxidative stress
Intestinal structure
Increases goblet cells and proliferating crypt cells
Protects against DSS-induced intestinal damage (colitis model) by lowering inflammation, crypt damage, and intestinal permeability.

Methionine is Found in These Foods:

Organism Concentration (per 100 grams)

Sunflower 20500 ppm
Brazil nut 10346 ppm
Sesame 9413 ppm
Fenugreek 8830 ppm
Butternut 6321 ppm
Spinach 6294 ppm
Swamp cabbage 5845 ppm
Horseradish-tree 5765 ppm
Evening primrose 5763 ppm
Taro 5510 ppm
Soybean 5380 ppm
Jute 5290 ppm
White mustard 5136 ppm
Opium poppy 5042 ppm
Common bean 4731 ppm
Carob 4700 ppm
Amaranth 4331 ppm
Watercress 4000 ppm
Common wheat 4000 ppm
Barley 4000 ppm
Oat 4000 ppm
Pistachio 3963 ppm
Winged bean 3884 ppm
Common pea 3879 ppm
Yardlong bean 3779 ppm
Chives 3750 ppm
Asparagus 3742 ppm
Fenugreek 3720 ppm
Common bean 3653 ppm
Mung bean 3571 ppm
Lentils 3500 ppm
Corn salad 3470 ppm
Peanut 3430 ppm
Winged bean 3357 ppm
Fennel 3302 ppm
Yardlong bean 3292 ppm
Mung bean 3145 ppm
Lambsquarters 3121 ppm
Lima bean 3017 ppm
Common walnut 2905 ppm
Chickpea 2860 ppm
White lupine 2850 ppm
Purslane 2814 ppm
Cashew nut 2787 ppm
Corn 2787 ppm
Rye 2785 ppm
Winged bean 2765 ppm
Malabar spinach 2755 ppm
Pigeon pea 2720 ppm
Cucurbita (Gourd) 2690 ppm
Lettuce 2667 ppm
Moth bean 2436 ppm
Adzuki bean 2426 ppm
Brussel sprouts 2285 ppm
Broad bean 2265 ppm
Common bean 2261 ppm
Endive 2254 ppm
Colorado pinyon 2200 ppm
Breadfruit 2195 ppm
Date 2190 ppm
Sacred lotus 2182 ppm
Hyacinth bean 2105 ppm
Sweet basil 2020 ppm
Oat 2000 ppm
Common thyme 1980 ppm
Pepper (C. frutescens) 1958 ppm
fish 1859 g
Soft-necked garlic 1824 ppm
Whitefish 1740 g
Bearded seal 1684 g
Sesame 1656 g
Cabbage 1604 ppm
Potato 1568 ppm
Dill 1549 ppm
Sweet orange 1510 ppm
Sweet orange 1510 ppm
Eggplant 1487 ppm
Kohlrabi 1445 ppm
Avocado 1438 ppm
whales 1353 g
Red beetroot 1341 ppm
Garden tomato (var.) 1322 ppm
Parsley 1282 ppm
Smelt 1240 g
Ginkgo nuts 1226 ppm
Star fruit 1210 ppm
Whelk 1205 g
Jicama 1200 ppm
Spirulina 1149 g
Common grape 1132 ppm
Brazil nut 1100 mg
Common pea 1088 ppm
Sacred lotus 1050 ppm
Mandarin orange (Clementine, Tangerine) 1048 ppm
Sunflower 1043 g
European chestnut 1028 ppm
Cucumber 1012 ppm
Brazil nut 1008 g
Deer 998 g
Mountain yam 970 ppm
Chicken (Cock, Hen, Rooster) 968 g
Macadamia nut 950 ppm
turkey 931 g
Greater sturgeon 924 g
sheep 918 g
Bison 914 g
Sockeye salmon 910 g
Buffalo 905 g
Calabash 900 ppm
Northern bluefin tuna 885 g
fish 878 g
Thunnus (Common tuna) 862 g
Hippoglossus (Common halibut) 861 g
Salmonidae (Salmon, Trout) 860 mg
boars 859 g
Jerusalem artichoke 858 ppm
European anchovy 855 g
Mule deer 838 g
Deer 837 g
Skipjack tuna 835 g
Yellowfin tuna 827 g
Rabbit 826 g
Cassava 825 ppm
birds 821 g
Pineapple 815 ppm
fish 810 g
Cottonseed 809 g
Beaver 792 g
Thunnus (Common tuna) 790 mg
Salmonidae (Salmon, Trout) 788 g
Albacore tuna 785 g
Greylag goose 783 g
Milkfish 779 g
Snapper 778 g
Duck 778 g
Sheepshead 770 g
Chicken (Cock, Hen, Rooster) 770 mg
boars 770 mg
Chum salmon 770 g
Wax gourd 770 ppm
King mackerel 770 g
Cichlidae (Tilapia) 766 g
Perciformes (Perch-like fishes) 762 g
fish 761 g
European rabbit 760 g
Bluefish 760 g
fish 753 g
Gadus (Common cod) 750 mg
Moose 749 g
Haddock 747 g
Spiny lobster 744 g
Sesame 740 mg
fish 738 g
Atlantic pollock 738 g
Ginger 737 ppm
Percoidei (Bass and others) 736 g
Pumpkinseed sunfish 736 g
Grouper 735 g
fish 734 g
cuttlefish 733 g
Burbot 733 g
Esox lucius 731 g
Atlantic herring 729 g
Orange roughy 728 g
Walleye 726 g
Domestic goat 726 g
Tilefish 725 g
Common ling 721 g
Cusk 721 g
Haddock 720 mg
birds 716 g
Stenotomus chrysops 716 g
Highbush blueberry 715 ppm
Clupeinae (Herring, Sardine, Sprat) 710 mg
birds 710 g
Pacific rockfish 707 g
Atlantic mackerel 706 g
Spot croaker 702 g
Dolphin fish 702 g
Florida pompano 701 g

Methionine Health Effects:

Anti cataract
Antidote
Anti eczemic
Anti hepatotic
Antioxidant
Anti Parkinsonian
Cancer preventive
Emetic
Essential
Glutathionigenic
Hepatoprotective
Lipotropic
Urine acidifier
Urine deodorant

Methionine Interacts with Diseases

Disease Inference Score

Liver Cirrhosis, Experimental 322.68
Prostatic Neoplasms 100.04
Breast carcinoma 86.04
Colorectal cancer 64.59
Stomach Neoplasms 63.56
Endometriosis 57.68
Autism 52.21
Diabetes Mellitus, Experimental 50.9
Hepatocellular carcinoma 48.59
Rheumatoid arthritis 46.47
Craniofacial Abnormalities 42.12
Diabetes Mellitus, Type 2 42.08
Arthritis, Juvenile 39.23
Carcinoma, Adenoid Cystic 39.06
Neoplasm Invasiveness 38.84
Reperfusion Injury 37.81
Neoplasm Metastasis 37.62
Disease Progression 34.91
Myocardial Ischemia 34.9
Obesity 34.75
Esophageal squamous cell carcinoma 34.64
Colonic neoplasm 34.41
Hernia, Diaphragmatic 31.65
Cell Transformation, Neoplastic 30.88
Leukemia, Myeloid, Acute 28.55
Alcoholic liver cirrhosis 27.7
Lung Neoplasms 27.59
Mesothelioma, Malignant 27.28
Amyotrophic lateral sclerosis 1 26.41
Carcinoma 26.29
Mammary Neoplasms, Experimental 24.7
Mammary Neoplasms, Animal 24.35
Abortion, Spontaneous 24.1
Osteoarthritis 24.04
Squamous cell carcinoma 23.99
Intellectual Disability 23.85
Fatty Liver 23.57
Salivary gland neoplasm 23.36
Renal cell carcinoma 23.0
Kidney Failure, Chronic 22.66
Liver Cirrhosis 22.0
Arsenic Poisoning 20.9
Melanoma 20.19
Nausea 20.1
Carcinoma, Non-Small-Cell Lung 19.58
Keloid 19.56
Esophageal Neoplasms 19.0
Brain Ischemia 18.8
Pulmonary Fibrosis 18.65
Pain 18.64
Precancerous Conditions 18.22
Vomiting 18.06
Myocardial Reperfusion Injury 18.05
Seizures 17.9
Calcinosis 17.07
Polycystic ovary syndrome 17.02
Infarction, Middle Cerebral Artery 16.78
Ovarian Neoplasms 16.53
Schizophrenia 16.3
Autism spectrum disorder 16.13
Oral Submucous Fibrosis 15.95
Medulloblastoma 15.69
Status Epilepticus 15.14
Tachycardia 15.03
Neoplasm Recurrence, Local 14.67
Carcinoma, squamous cell of head and neck 14.48
Crohn's disease 14.41
Poisoning 14.41
Tremor 14.39
Hypotension 14.14
Copper-Overload Cirrhosis 14.03
Adenocarcinoma 13.84
Renal Insufficiency 13.45
Cardiac arrhythmia 13.41
Marfan Syndrome 13.31
Catalepsy 13.22
Radiation Injuries, Experimental 13.2
Diarrhea 12.98
Edema 12.92
Heart Valve Diseases 12.89
Pancreatic carcinoma 12.77
Headache 12.54
Astrocytoma 12.39
Leukemia, Myelomonocytic, Juvenile 12.26
Nasopharyngeal carcinoma 12.23
Sezary Syndrome 12.23
Trigeminal Neuralgia 12.23
Endometrial neoplasm 11.88
Spinocerebellar Ataxia 17 11.69
Primary biliary cirrhosis 11.62
Leukemia, Promyelocytic, Acute 11.58
Hyperkinesis 11.57
Osteochondrodysplasias 11.44
Pulmonary Emphysema 11.11
Glioblastoma multiforme 10.93
Polycystic Kidney, Autosomal Recessive 10.89
Prenatal Exposure Delayed Effects 10.84
Mesothelioma 10.72
Small cell lung carcinoma 10.55
Asthma 10.51
Respiratory Distress Syndrome, Adult 10.5
Glioma 10.44
Neural tube defect, folate-sensitive 10.44
Dyskinesia, Drug-Induced 10.4
Weight Loss 10.4
Noise-induced hearing loss 10.37
Leukemia-Lymphoma, Adult T-Cell 10.04
Alzheimer's Disease 9.98
Infertility, Female 9.96
Wounds and Injuries 9.89
Weight Gain 9.84
Neuroblastoma 9.8
Genetic Predisposition to Disease 9.78
Chronic lymphocytic leukemia 9.68
Myoclonic Epilepsies, Progressive 9.57
Muscular Dystrophy, Facioscapulohumeral 9.47
Chloracne 9.38
Thrombocytopenia 9.35
Neurofibromatosis 1 9.33
Plasmodium Falciparum Blood Infection Level 9.22
Dermatitis, Contact 9.2
Skin Diseases 9.17
Acute coronary syndrome 9.01
Neuroectodermal Tumors, Primitive 8.94
Thoracic aortic aneurysm 8.91
Bone Diseases, Developmental 8.67
Atherosclerosis 8.63
Osteosarcoma 8.62
Amnesia 8.55
Listeriosis 8.54
Lymphoma, T-Cell, Cutaneous 8.5
Necrosis 8.46
Fever 8.45
Turner Syndrome 8.44
Autoimmune disease 8.42
Anemia 8.4
Pleural Diseases 8.38
Lewy body dementia 8.36
Heart failure 8.3
Urinary Bladder Neoplasms 8.25
Basal cell carcinoma 8.16
Iga glomerulonephritis 8.16
Myopathies, Structural, Congenital 8.14
Osteoporosis 8.11
Ataxia 8.09
Down syndrome 8.08
Epidermolysis Bullosa, Junctional 8.06
Cholangiocarcinoma 8.01
Brain Diseases 7.99
Peters anomaly 7.99
Furlong syndrome 7.95
Hepatomegaly 7.87
Lung adenocarcinoma 7.87
Heat Stroke 7.86
Obesity, Morbid 7.86
Psoriatic arthritis 7.85
Asphyxia Neonatorum 7.81
Ovarian Cysts 7.81
Lymphatic Metastasis 7.78
Microsatellite Instability 7.78
Tachycardia, Ventricular 7.78
Mouth Neoplasms 7.77
Myoclonus 7.69
Ulcerative colitis 7.69
Anthracosis 7.68
Cholestasis 7.66
Long QT Syndrome 7.65
Ceroid Lipofuscinosis, Neuronal, 6 7.62
Hemorrhage 7.62
Drug dependence 7.6
Fatigue 7.6
Charcot-Marie-Tooth Disease 7.55
Cardiac hypertrophy 7.51
Psychoses, Substance-Induced 7.51
Meningioma 7.5
Mycobacterium Infections, Nontuberculous 7.46
Epilepsy, Temporal Lobe 7.32
Hepatitis, Chronic 7.32
Epidermolysis Bullosa, Junctional, Non-Herlitz Type 7.26
Ventricular Fibrillation 7.23
Beckwith-Wiedemann Syndrome 7.21
Pancreatic Agenesis, Congenital 7.2
Aortic Valve Insufficiency 7.19
Neuromyelitis Optica 7.19
Brain Injuries 7.11
Neuroacanthocytosis 7.1
Netherton Syndrome 7.07
Multiple sclerosis 7.06
Paroxysmal ventricular fibrillation 7.06
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 7.03
Chondrosarcoma, Mesenchymal 7.02
Alternating hemiplegia of childhood 6.98
Prostatic Intraepithelial Neoplasia 6.98
Drug Eruptions 6.97
Shprintzen Golberg craniosynostosis 6.95
Carcinoma, Transitional Cell 6.91
Heart Arrest 6.91
CUTIS LAXA, AUTOSOMAL DOMINANT 1 6.9
Hypokalemia 6.9
Silicosis 6.87
Epidermolysis bullosa with pyloric atresia 6.84
Pruritus 6.8
Diabetic Angiopathies 6.79
Neutropenia 6.79
Spondylometaphyseal dysplasia, Kozlowski type 6.79
Anodontia 6.77
Colorectal cancer, hereditary nonpolyposis, type 1 6.76
Coffin-Siris syndrome 6.75
Non-alcoholic fatty liver disease 6.74
Hereditary Breast and Ovarian Cancer Syndrome 6.71
Lipid Metabolism, Inborn Errors 6.71
Hand Deformities, Congenital 6.69
Torsades de pointes 6.68
Silver-Russell Syndrome 6.67
Tooth Abnormalities 6.66
Uremia 6.65
Lymphoma, Follicular 6.62
Disease Models, Animal 6.56
Breast Neoplasms, Male 6.55
Vision Disorders 6.52

Genes:

TNF
RXRA
IL6
IL1B
TGFB1
NR0B2
GPT
COL1A1
ACTA2
CTGF
CCL2
ABCC4
FGF21
MAPK1
MAPK3

Genes:

There are a few genes that can affect the amount of dietary methionine you want to get.
The MTHFR gene is one significant gene that affects the conversion of homocysteine to methionine. If you have a poor functioning gene, you will require more folate. If you don’t get adequate folate, you will have higher homocysteine and lower methionine.
Low methionine intake was significantly associated with an increased risk of Colorectal Tumor in MTHFR 677 (AA) individuals compared to people with low intake and the normal genotype.
The MTRR gene and MTR gene convert homocysteine to methionine and if they are not functioning well, you may have higher levels of homocysteine and lower methionine.

Google Sites

Report abuse