L-Methionine  甲硫胺酸  強肝解毒 強壯劑

蛋氨酸(Methionine)，又稱甲硫丁氨酸，是唯一的含硫氨基酸，有L型及D型兩種光學異構物，一般而言，天然存在者為L型Methionine(L-Methionine)，另外可利用化學法生產DL-Methionine，因二者皆具有相同的活性，如欲從DL-Methionine取得純化的L-Methionine，需進一步進行光學分割。

生物體每天都要從食物中攝取一定數量的氨基酸，以維持蛋白質的生物合成與代謝作用，但有些氨基酸在天然食物中的含量很少，因此需額外補充，如Methionine。因此，Methionine廣泛應用於食品之營養補充與畜產飼料。在二十多種氨基酸中，離氨酸(Lysine)與蛋氨酸(Methionine)是工業化生產價值較高的二種。

Methionine具有強壯劑、促進發育劑(特別是毛髮、指甲等)、強肝解毒劑等功能，因此被廣泛應用於食品、飼料添加劑或醫藥方面。

Methionine在體內變成Cystine，是體內進行氧化還原不可或缺的氨基酸，能於代謝過程中，發揮解毒的功能。Methionine屬於“必需氨基酸”，在人體內無法合成，必須由食物中攝取，當成人缺乏此種氨基酸時，會出現疲倦、肌肉萎縮、貧血、抵抗力減弱等症狀。 

臨床運用：

1. High-histamine schizophrenia(histadelia):

 + calcium, zinc and Mn. 傳說有效 

2. Parkinson’s disease: 1g/day, to 5g/day x 2個月 改善15個患者中的10個的症狀(無控制組實驗) 可增加L-dopa的製造 

3. AIDS myelopathy: 6g/day x 6 months  可改善此類患者的認知功能 

4. Acetaminophen的解毒劑 

劑量： 1-6g/day

毒性：  

大劑量（5-6g/day）會造成高鈣尿（Hypercalciuria），且長期大劑量的安全性未知。

描述

L-蛋氨酸是一種蛋白質氨基酸。 它被歸類為人類必需氨基酸，因此必須在飲食中提供。 根據聯合國糧食及農業組織 (FAO) 和世界衛生組織 (WHO) 的數據，建議成人每日 L-蛋胺酸攝取量為每公斤 13 毫克，即每天約 1 克。 實際攝取量較高。 這主要來自膳食蛋白質。 L-蛋氨酸的豐富來源包括起司、雞蛋、魚、肉和家禽。 L-蛋氨酸也存在於水果和蔬菜中，但含量不那麼豐富。 蔬菜、蔬菜汁和發酵食品中存在少量遊離L-蛋胺酸。

除了在蛋白質合成中作為前體的作用外，L-蛋氨酸還參與廣泛的生化反應，包括S-腺苷甲硫氨酸（SAM 或SAMe）、L-半胱氨酸、穀胱甘肽、牛磺酸和硫酸鹽的生產。 SAM 本身作為甲基供體（參見 SAMe），參與肌酸、腎上腺素、褪黑激素、多胺精胺和亞精胺以及其他幾種物質的合成。

L-蛋氨酸也是一種生糖氨基酸，可能參與D-葡萄糖和肝醣的形成。 L-蛋氨酸能夠減少對乙醯氨基酚和甲氨蝶呤等肝毒素的肝毒性作用，因此建議在對乙醯氨基酚產品中添加蛋氨酸。 然而，最近的一些研究表明，L-蛋氨酸攝取量增加可能會促進腸道癌症的發生。 這還不清楚。 此外，L-蛋氨酸的代謝物之一L-同型半胱氨酸被認為是冠心病和其他血管疾病的重要因素。

L-蛋胺酸是一種含硫胺基酸，極難溶於水。 其分子式為C5H11NO2S，分子量為149.21道爾頓。 L-蛋胺酸又稱為2-氨基-4-(甲硫基)丁酸、α-氨基-γ-甲硫基丁酸、(S)-2-氨基-4-(甲硫基)丁酸和γ-甲硫基-α-氨基丁酸。 它縮寫為 Met，單字母縮寫為 M。術語 L-蛋氨酸和蛋氨酸可互換使用。 D-立體異構體D-甲硫胺酸不具有上述蛋白質合成和生化反應的生物活性。 然而，D-蛋氨酸和L-蛋氨酸可能具有抗氧化活性。

作用和藥理學

行動

L-蛋氨酸可以防止肝毒素（例如對乙醯氨基酚）的毒性作用。 蛋氨酸可能具有抗氧化活性。

作用機制

L-蛋氨酸可能的抗肝毒性活性的機制尚不完全清楚。 人們認為，高劑量對乙醯氨基酚在肝臟中的代謝會導致肝臟穀胱甘肽水平降低並增加氧化壓力。 L-蛋氨酸是L-半胱氨酸的前驅物。 L-半胱氨酸本身可能具有抗氧化活性。 L-半胱胺酸也是抗氧化劑穀胱甘肽的前驅物。 L-蛋氨酸和 L-蛋氨酸代謝物的抗氧化活性似乎解釋了其可能的抗肝毒性活性。 最近的研究表明，蛋氨酸本身由於其硫及其螯合能力而具有自由基清除活性。

藥物動力學

攝取後，L-蛋胺酸透過主動轉運過程從小腸腔吸收到腸上皮細胞。 L-蛋氨酸的一些代謝發生在腸上皮細胞內。 未代謝的物質經由門靜脈循環轉運至肝臟。 在肝臟中，L-蛋胺酸與其他胺基酸一起參與蛋白質生物合成。 它也可能參與多種代謝反應，包括 SAMe、L-同型半胱氨酸、L-半胱氨酸、牛磺酸和硫酸鹽的形成。 它還可以代謝產生D-葡萄糖和肝醣。 L-蛋氨酸不在肝臟中代謝，被轉運到身體的各個組織，在那裡參與與上述類似的反應。

適應症和用途

除非醫生特別建議，否則沒有任何跡象表明可以補充蛋氨酸。 在某些對乙醯氨基酚中毒病例中，它作為解毒劑是有效的。 但是，由於一些研究表明它可能會促進某些癌症，因此不建議將其用作補充劑。

研究概要

研究發現，在乙醯胺酚中毒後 10 小時內服用口服蛋胺酸，在預防嚴重肝損傷和死亡方面與 N-乙醯半胱氨酸一樣有效。 有初步證據表明，蛋氨酸也可能有助於預防甲氨蝶呤和慶大霉素等的一些不良副作用。

另一方面，大量攝取蛋胺酸會導致氧化劑同型半胱胺酸水平升高。 有人擔心飲食中攝取大量蛋胺酸會促進某些癌症，並且有一些非常初步的實驗數據支持這種擔憂。 還有一些流行病學數據顯示飲食中蛋胺酸含量增加與胃癌風險增加之間存在關聯。 需要更多的研究。

禁忌症、注意事項、不良反應

禁忌症

L-蛋胺酸對於患有遺傳性疾病高胱胺酸尿症的患者是禁忌的。 對含蛋氨酸產品的任何成分過敏的人也是禁忌的。

預防措施

孕婦和哺乳期婦女應避免服用 L-蛋氨酸補充劑，除非有醫生處方。

患有腫瘤疾病的人應避免補充 L-蛋氨酸。 同型半胱氨酸水平升高的人也應避免使用，患有冠心病的人也應謹慎使用。

對於精神分裂症患者以及肝腎衰竭患者，補充 L-蛋胺酸應非常謹慎。 無論如何，L-蛋氨酸補充劑只能在醫生推薦和監督下使用。

不良反應

L-蛋胺酸每天高達 250 毫克的劑量通常耐受性良好。 較高劑量可能會導致噁心、嘔吐和頭痛。 健康成年人每天服用 8 克 L-蛋氨酸，連續四天，發現血清葉酸水平和白血球增多症降低。 健康成年人每天服用 13.9 克 L-蛋氨酸，連續五天，發現血清 pH 值和鉀發生變化，尿鈣排泄增加。 精神分裂症患者每天服用 10 至 20 克 L-蛋胺酸，持續兩週，就會出現功能性精神病。 單次服用 8 克會導致肝硬化患者發生腦病變。

互動

藥物

對乙醯氨基酚和甲氨蝶呤：L-蛋氨酸可以降低對乙醯氨基酚過量或服用甲氨蝶呤的患者的肝毒性。 理論上，它也可以降低其他潛在肝毒性藥物的肝毒性。

慶大霉素：蛋胺酸可以防止慶大霉素的耳毒性作用。

營養補充品

研究發現，低蛋白飲食的健康女性在飲食中補充 L-蛋胺酸可以降低甘胺酸水平。

高鹽和亞硝酸鹽/硝酸鹽飲食中攝取大量 L-蛋氨酸可能會增加胃癌的風險。

藥物過量

沒有服用過量的報告。

劑量和給藥

L-蛋胺酸補充劑只能在醫生的建議下服用。

如何提供

膠囊 — 500 毫克

粉末

片劑 — 200 毫克、500 毫克

DESCRIPTION 

L-methionine is a protein amino acid. It is classified as an essential amino acid for humans and therefore must be supplied in the diet. According to the Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO), recommended daily L-methionine intake is 13 mg per kg or about one gram daily for adults. Actual intake is higher. This is principally derived from dietary proteins. Rich sources of L-methionine include cheeses, eggs, fish, meat and poultry. L-methionine is also found in fruits and vegetables, but not as abundantly. Small amounts of free L-methionine occur in vegetables, vegetable juices and fermented foods.

In addition to its role as a precursor in protein synthesis, L-methionine participates in a wide range of biochemical reactions, including the production of S-adenosylmethionine (SAM or SAMe), L-cysteine, glutathione, taurine and sulfate. SAM itself, as a methyl donor (see SAMe), is involved in the synthesis of creatine, epinephrine, melatonin and the polyamines spermine and spermidine, among several other substances.

L-methionine is also a glycogenic amino acid and may participate in the formation of D-glucose and glycogen. The ability of L-methionine to reduce the liver-toxic effects of such hepatotoxins as acetaminophen and methotrexate has led to the suggestion that methionine should be added to acetaminophen products. However, there is some recent research suggesting that elevated L-methionine intake may promote intestinal carcinogenesis. This is unclear. Further, one of the metabolites of L-methionine, L-homocysteine, has been implicated as a significant factor in coronary heart disease and other vascular diseases.

L-methionine is a sulfur-containing amino acid that is minimally soluble in water. Its molecular formula is C₅H₁₁NO₂S, and its molecular weight is 149.21 daltons. L-methionine is also known as 2-amino-4-(methylthio)butyric acid, alpha-amino-gamma-methylmercaptobutyric acid, (S)-2-amino-4-(methylthio)butanoic acid and gamma-methylthio-alpha-aminobutyric acid. It is abbreviated as Met and its one-letter abbreviation is M. The terms L-methionine and methionine are used interchangeably. The D-stereoisomer, D-methionine, does not possess biological activity with regard to protein synthesis and the biochemical reactions mentioned above. However, D-methionine, as well as L-methionine, may possess antioxidant activity.

ACTIONS AND PHARMACOLOGY

ACTIONS

L-methionine may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity.

MECHANISM OF ACTION

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 lead 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 its chelating ability.

PHARMACOKINETICS

Following ingestion, L-methionine is absorbed from the lumen of the small intestine into the enterocytes by an active transport process. Some metabolism of L-methionine takes place within the enterocytes. That which is not metabolized is transported to the liver via the portal circulation. In the liver, L-methionine, along with other amino acids, participates in protein biosynthesis. It may also participate in a wide variety of metabolic reactions, including the formation of SAMe, L-homocysteine, L-cysteine, taurine and sulfate. It can also be metabolized to produce D-glucose and glycogen. L-methionine not metabolized in the liver is transported to the various tissues of the body where it is involved in reactions similar to those described above.

INDICATIONS AND USAGE

There are no indications for the use of supplemental methionine unless specifically recommended by a physician. It is effective as an antidote in some cases of acetaminophen poisoning. But, because some research suggests that it may promote some cancers, its use as a supplement is inadvisable.

RESEARCH SUMMARY

When given within 10 hours of acetaminophen poisoning, oral methionine has been found to be as effective as N-acetylcysteine in preventing severe liver damage and death. There is preliminary evidence that methionine might also help protect against some of the adverse side effects of methotrexate and gentamicin, among others.

On the other hand, high intake of methionine can lead to increased levels of the oxidant homocysteine. There is some fear that high intake of dietary methionine can promote some cancers, and there is some very preliminary experimental data to support that fear. There is also some epidemiological data suggesting a link between increased dietary methionine and increased risk of gastric cancer. More research is needed.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICATIONS

L-methionine is contraindicated in those with the genetic disorder homocystinuria. It is also contraindicated in those who are hypersensitive to any component of a methionine-containing product.

PRECAUTIONS

L-methionine supplements should be avoided by pregnant women and nursing mothers unless they are prescribed by a physician.

L-methionine supplementation should be avoided by those with neoplastic disease. It should also be avoided by those with elevated homocysteine levels and used with caution in those with coronary heart disease.

Supplemental L-methionine should be used with great caution in those with schizophrenia and those with hepatic and renal failure. In any case, L-methionine supplements should only be used if recommended and monitored by a physician.

ADVERSE REACTIONS

Doses of L-methionine of up to 250 mg daily are generally well tolerated. Higher doses may cause nausea, vomiting and headache. Healthy adults taking 8 grams of L-methionine daily for four days were found to have reduced serum folate levels and leucocytosis. Healthy adults taking 13.9 grams of L-methionine daily for five days were found to have changes in serum pH and potassium and increased urinary calcium excretion. Schizophrenic patients given 10 to 20 grams of L-methionine daily for two weeks developed functional psychoses. Single doses of 8 grams precipitated encephalopathy in patients with cirrhosis.

INTERACTIONS

DRUGS

Acetaminophen and methotrexate: L-methionine may decrease hepatic toxicity in those with acetaminophen overdosage or in those taking methotrexate. Theoretically, it may decrease hepatic toxicity in the case of other potential hepatotoxic drugs, as well.

Gentamicin: Methionine may protect against the ototoxic effects of gentamicin.

NUTRITIONAL SUPPLEMENTS

Dietary supplementation with L-methionine was found to decrease glycine levels when given to healthy women on a low-protein diet.

High L-methionine intake in a diet high in salt and nitrites/nitrates may increase the risk of stomach cancer.

OVERDOSAGE

There are no reports of overdosage.

DOSAGE AND ADMINISTRATION

L-methionine supplements should only be taken with a physicians recommendation.

HOW SUPPLIED

Capsules — 500 mg

Powder

Tablets — 200 mg, 500 mg