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amino acid
methionine
Nutrition

definition

Methionine: an essential sulfur-containing amino acid
related substance: S-adenosyl methionine (SAMe)

» metabolism:
• One of the sulfur containing amino acids, methionine is essential because we cannot synthesize it from aspartic acid. However, there have been reports of people surviving on only potatoes which are deficient in methionine. This may be because bacteria in the gut can synthesize significant amounts.
• Methionine is converted into S-adenosyl methionine (SAMe), which is considered to be the activated form of methionine. This happens in the first step of the metabolism of methionine. This step requires energy in the form of ATP. In this activation of methionine, an adenosyl moiety is transferred from the ATP molecule.
• SAMe is an important biological methylating agent. Its methyl group, which is attached in a sulfonium linkage with high-energy characteristics, may be donated to any of a large number of methyl-group acceptors in the presence of the appropriate enzyme.
• SAMe was first discovered by G. Cantoni and colleagues in 1952 in Italy. Interestingly enough, when high doses of methionine are given orally, levels of SAMe do not go up correspondingly as one would expect. SAMe is an extremely potent methyl donor.

» function:
• Methionine is an essential sulfur-containing amino acid that facilitates the helps initiate the translation of messenger RNA by being the first amino acid incorporated into the N-terminal position of all proteins. The terminal methyl group of the methionine side chain often participates in biochemical methyl transfer reactions making methionine a member of the "methyl donor" class of biochemicals.
• Methionine is converted into S-adenosyl methionine (SAMe), which is considered to be the activated form of methionine. This happens in the first step of the metabolism of methionine. This step requires energy in the form of ATP. In this activation of methionine, an adenosyl moiety is transferred from the ATP molecule. SAM synthesis is one of the most potent methyl donors and is involved in many methylation reactions. Its methyl group, which is attached in a sulfonium linkage with high-energy characteristics, may be donated to any of a large number of methyl-group acceptors in the presence of the appropriate enzyme. SAM is intimately involved in the synthesis of brain chemicals and also in detoxification reactions. This compound has pronounced analgesic properties and is currently being investigated in Italy. It has been commercially available in Europe since 1975 and has recently become available in the U.S.
• Methionine performs as a sulfur donor and, as such, is the source of sulfur for biosynthesis of cysteine.
• Methionine is also considered a member of the group of compounds called lipotropics.

» Chinese:
• Nourishes the Xue (Blood); benefits the Jing (Essence); cools the Xue (Blood); relaxes the Liver; calms the Hun (Soul).

» requirements:
• RDAs: 22 mg/kg for children and 10 mg/day/kg or 1.5 g per day for adults.
• WHO recommends 9 g per day
• Homocysteine in the diet can eliminate the requirement for methionine
• Average intake in the U.S.: 2.7 to 5 g per day
• Intake of cysteine and methionine:
• Omnivores: 4.3 g
• Lacto-ovo-vegetarian: 3.2 g
• Vegans: 2.7 g

» food sources:
• Dairy, fish and meat are considered the richest dietary sources of methionine.
• Sunflower seeds are also a good source of methionine. Soybeans are a poor source and soy-based infant formulas are generally low in methionine.
• Egg yolks are particularly high in sulfur. Methionine and cysteine make up 91% of the sulfur in the yolk.
• Average intake in the U.S.: 2.7 to 5 g per day.
• Bacteria in the gut may be able to synthesize significant amounts.
• Homocysteine in the diet can eliminate the requirement for methionine.

Best Sources of Methione:
Food Amount mg
Tuna 3 oz 733
Cheese, Cheddar 3 oz 555
Salmon 3 oz 505
Wild game 3 oz 444
Shrimp, mixed cooked 3 oz 400
Cheese, Ricotta 1/2 cup 350
Pork 3 oz 333
Meat, luncheon 3 oz 241
Granola 1 cup 200
Egg 1 med 200
Milk, whole 1 cup 200
Chocolate 1 cup 200
Cashews 1/2 cup 188
Walnuts 1/2 cup 170
Turkey 1 oz 167
Sausage 3 oz 166
Almonds 1/2 cup 160
Wheat germ toasted 1/4 cup 158
Duck 3 oz 157
Chicken 3 oz 120
Filberts 1/2 c (70 g) 120
Cheese, cottage 1/2 c up 100
Sesame seed butter 2 Tbsp (30 g) 100
Peanut Butter 2 Tbsp 94
Potato, baked 1 med 73
Sweet potato 1 med 48
Avocado 1/2 med 25
Mushrooms, Shitake 8 med 36
(USDA: Composition of Foods. USDA Handbook #8 Washington DC, ARS, USDA, 1976-1986)

» deficiency:
• Methionine deficiency is usually related to overall protein malnutrition. Experimentally, a methionine deficiency causes premature atherosclerosis in monkeys, especially if they are also deficient in vitamin B6. Methionine deficiency can also cause a folate deficiency since a deficiency causes 5-methyl-tetrahydrofolate to accumulate in the liver.

» therapeutics:
Acrodermatitis enteropathica: a condition similar to pronounced atopic dermatitis and related to a genetic defect in zinc absorption. Methionine can reduce polyamines which may exacerbate the symptoms.
Hypercholesteremia: as a lipotropic agent.
Migraine headaches: may require long term treatment to be effective.
Radiation effects

» dosage:
• Maintenance dose: Dietary sources of methionine are usually adequate so supplemental methionine is usually not considered necessary. Optimal levels of intake have not been established.
• Therapeutic dose: 0.5 - 3 g per day.

» side effects: Methionine is generally considered to be free of side effects for most individuals and 1 - 3 g per day is usually tolerated well by most adults. Some sensitive individuals may experience gas, bloating and digestive discomfort at levels as low as 500 mg per day. Diets high in methionine may be associated with an increased occurrence of atherosclerosis, especially with concurrent deficiencies of vitamin B6, vitamin B12 and folic acid.

» toxicity:
• Although it rarely occurs, nausea and gastrointestinal irritation are signs of methionine toxicity.
• In cases of strong family history of coronary heart disease, it is wise to check homocysteine levels before and during treatment.
• Rats fed methionine as 50% of dietary protein (equivalent human dose of 25 g per day) exhibited hyperactivity, anorexia, reduced growth, iron accumulation in the spleen

» contraindications:
• Osteoporosis: large doses increases urinary excretion of calcium.

» interactions:
nutrient affected by drug: Vidarabine

• mechanism: Vidarabine is known to interfere with methionine synthesis.
(Med Lett Drugs Ther 1977 May 20;19(10):42-43; Cantoni GL, et al. N Engl J Med 1982 Oct 21;307(17):1079.)

• nutritional concerns: Individuals taking vidarabine for an extended period of time should consult with with their prescribing physician to discuss options for countering the potential adverse effects of this drug. Some nutritionally oriented physicians have found value in monitoring serum methionine in their patients taking vidarabine.


Footnotes

[No author given] Vidarabine (Vira-A). Med Lett Drugs Ther 1977 May 20;19(10):42-43.

Bidard JN. et al. [Effect de la SAM sur le catabolisme de la dopamine.] J Pharmacol. (Paris) 1977; 8, I:83-93.

Burger R., Nowak H. A new medical approach to the treatment of osteoarthritis: Report of an open phase 1V study with ademetionin (Gumbaral) SAM. Am J Med 1987; 83:(suppl 5A), 84-88.
Abstract: Over 20,000 patients with osteoarthritis of the knees, hip, spine and fingers were studied over an 8 week period. Patients received 400 mg three times daily for first week, then 400mg twice daily for second week and 200mg twice daily from the third week on. No added treatment was permitted. The results revealed 71% of the patients had very good or good response which is comparable to NSAIDS but without the side effects.

Cantoni GL, Aksamit RR, Kim IK Methionine biosynthesis and vidarabine therapy. N Engl J Med 1982 Oct 21;307(17):1079. (Letter)

Caruso I, Pietrogrande V. Double blind, multicenter study comparing SAM, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987 83:(suppl 5A), 66-71. [Article in Italian]

Glorioso S, et al. Double blind, multicenter study of the activity of SAM in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985; 5, 39-49.

Kagan BL, et al. Oral SAM in depression: A randomized, double blind placebo-controlled trial. Am J Psychiatry 1990; 147:591-595.

Marcolongo R, et al. Double blind, multicenter study of the activity of SAM in hip and knee osteoarthritis. Current Ther Res 1985; 37:82-94.

Marz, Russell. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.

Muller-Fassbender H. Double blind, clinical trial of SAM versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987; 83 (suppl. 5A), 81-83.

Rosenbaum JF, et al. An open label pilot study of oral SAM in major depression. Psychopharmacol Bull 1988; 24:189-194.

Salmaggi P, et al. Double blind, placebo-controlled study of SAM in depressed postmenopausal women. Psychotherapy Psychosom 1993; 59:905-113.

USDA: Composition of Foods. USDA Handbook #8 Washington DC, ARS, USDA, 1976-1986.