MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Methionin

Synonyma a názvy preparátů

  • Dl-methionine
  • Racemethionine
  • M
  • Smethionine
  • L-methionine
  • Methioninum
  • Acimethin®
  • Acimol®
  • Ammonil®
  • DLMethionine
  • Tablets®
  • MCaps®
  • Methigel®
  • Methio-Form®
  • Methiotrans®
  • Methnine®
  • Neutrodor®
  • Pedameti®
  • Uracid®
  • Uromethin®

Methionin ve stravě

  • Vejce (nejvyšší obsah) [1], [3]
  • Ryby
    • Tuna, yellow fin or canned, cod, haddock, perch, pike [3]
  • Ořechy (semena)
    • Sezam (nejvíce) [3]
    • Brazil nuts (3x méně než sezam) [3]
  • Obilniny
  • Maso
    • Zvířata živená obohacenou stravou o methionin vyšší obsah ve tkáních
  • Jogurty
  • Kvasnice (0.75%)
  • Velmi málo v zelenině a v luštěninách [1], [2]
    • Turnip greens and spinach (relativně ještě něco) [3]
    • Broccoli, squash and zucchini (něco málo) [3]

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[3]

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[4]

Literatura:

[1] 1. Methionin (esenciální aminokyselina), zdroj a účinky [Internet]. [citován 10. únor 2013]. Získáno z: www.wellness-trend.cz/zdravi/aloe-vera/methionin/
[2] Methionine - Wikipedia, the free encyclopedia [Internet]. [citován 10. únor 2013]. Získáno z: en.wikipedia.org/wiki/Methionine
[3] Foods Containing Methionine | LIVESTRONG.COM [Internet]. [citován 10. únor 2013]. Získáno z: www.livestrong.com/article/267952-foods-containing-methionine/
[4] Methionine | Whole Food Catalog [Internet]. [citován 10. únor 2013]. Získáno z: wholefoodcatalog.info/nutrient/methionine/

Metabolismus methioninu

Charakteristika

  • Essential amino acid (l-form) and nutrient
  • Plasma Met concentrations of 10–40 µM are considered normal [25]
  • Lipotrope
  • Prevents or corrects fatty liver in choline deficiency
  • Supplies sulfhydryl and methyl groups to the liver for metabolic processes
  • Oxidation of methionine residues to methionine sulfoxide is reversible; thus, cyclic oxidation and reduction of methionine residues leads to consumption of ROS and thereby increases the resistance of proteins to oxidation. [13]

Kofaktory a substráty v metabolismu methioninu a epigenetika

  • Involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine [26]
  • Can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications [27]
    • Retinoic acid
    • Resveratrol
    • Curcumin
    • Sulforaphane
    • Tea polyphenols :27::
  • Epigentické změny během stárnutí organismu [27]


S-adenosylmethionine (SAMe)

  • First step in methionine catabolism in a reaction catalyzed by methionine adenosyltransferase (MAT) [8]
    • Dále vznikne methylthioadenosine (MTA) a není již donorem met. [8]
  • Forming monoamine neurotransmitters
  • Bez 5-MTHF klesá SAMe in the cerebrospinal fluid
    • Klesaá i hladina neurotransmiterů in the cerebrospinal fluid
      • Zhoršení depression [3]
  • SAMe supplementation improve depressive symptoms [3]
  • Regulates hepatocyte growth, death, and differentiation [8]
    • Animal models of liver injury shows hepatoprotective properties [8]
    • Effective in patients with cholestatic liver diseases [8]
  • Decreased hepatic SAMe biosynthesis is a consequence of all forms of chronic liver injury [8]
    • Liver is predisposed to further injury and develops spontaneous steatohepatitis and hepatocellular carcinoma [8]
    • Impaired SAMe metabolism (mutations of glycine N-methyltransferase (GNMT)), can also lead to liver injury [8]
  • Radical-based catalysis [8]
    • Radical-based catalysis, 5-deoxyadenosine is formed and this, too, is cleaved and reutilized [8]
  • S-adenosylmethionine (SAM) serves as an oxidizing agent in DNA repair and the biosynthesis of vitamins, coenzymes and antibiotics [9]
    • 5'-deoxyadenosyl radical, from SAM [9]
  • Key role for deranged S-adenosylmethionine metabolism in the pathogenesis of liver disease [11]
  • SAMe activate homocysteine flux through the transsulfuration pathway
  • Quantitatively most important pathways for S-adenosylmethionine-dependent transmethylation in mammals
    • Syntheses of creatine
      • Guanidinoacetate methyltransferase [12]
    • Phosphatidylcholine
      • Phosphatidylethanolamine methyltransferase [12]
    • Sarcosine
      • Glycine N-methyltransferase [12]
        • Surplus methyl groups are transferred from SAM to glycine, yielding N-methyl glycine (sarcosine) [16]
  • Transamination pathway
    • Significant only at high methionine concentrations
    • Produces a number of toxic endproducts [16]
  • SAM is also necessary for utilization of the antioxidant glutathione via glutathione S-transferase [13]
  • (SAM),4 which is essential for the biosynthesis of key components such as phospholipids [16]
  • SAM is essential for the regulation of chromatin function [16]
  • SAM as a substrate for the covalent methylation of DNA and proteins [16]
    • Increases in the intracellular concentrations of SAM above the normal
      • Increase in the activity of the methyltransferase enzymes
        • Hypermethylation of the substrate
          • May interfere with the process of chromatin remodeling
          • Cause changes in the subsequent expression of genes (epigenetic programming) [16]
            • Např.: the large-offspring syndrome [16]
            • Důležité pro postupy při in vitro fertilizaci
              • Avoiding an excess of methionine and providing sufficient glycine in the medium may be very important in minimizing the impact of embryo culture [16]
  • SAM decarboxylation is an important step in the synthesis of polyamines which are involved in cellular differentiation and growth [25]

Serin

  • Serine is the major source of one-carbon units for methylation reactions that occur via the generation of S-adenosylmethionine [21]

Homocystein

  • The size of the homocysteine pool is determined
    • By the rate of its production
    • Rate of reconversion to methionine
    • Rate of transsulfuration of homocysteine to produce cysteine and taurine [16]

Remethylation of homocysteine

  • 5-methyltetrahydrofolate (5-MTHF, L-methylfolate) or betaine
    • Methyl donor [6]
  • Forms a methionine cycle
  • Obě metylázy suprimovány adenosylmethioninem [6]
  • All tissues [6]

Transsulfuration sequence

  • Cystathionine synthase
    • Stimulována adenosylmethioninem [6]
    • Homocysteine is then removed by combination with serine to produce cystathionine, which is cleaved to form ?-ketobutyrate and cysteine [15]
  • Cystathionase
    • Stimulována adenosylmethioninem [6]
  • Irreversibly catabolize the homocysteine
    • Synthesizing cysteine [6]
      • 2 met na 1 cys [1]

Cystein

  • Ability to form disulfide bonds
    • Crucial role in protein structure and in protein-folding pathways [16]
  • Cysteine may be converted to
    • Glutathione
      • Liver plays a central role, by increasing cysteine availability for tumor GSH synthesis, function in combination as a metastatic-growth promoting mechanism [19]
      • Acceleration of GSH efflux facilitates selective GSH depletion in metastatic cells [19]
    • Taurine
      • Present in many tissues at higher concentrations than any of the other amino acids
      • Essential nutrient for cats [16]
        • A nebo právě proto, že ho kočky nemají, tak je pro ně snadno toxické podání methioninu ?
  • L-cysteine
    • Conditionally essential or (indispensible) sulphur amino acid
    • Key role in the metabolic pathways involving methionine, taurine and glutathione (GSH)
    • May help fight chronic inflammation by boosting antioxidant status
    • Critically ill patients receiving enteral or parenteral nutrition, enriched with cysteine, exhibit decreased cysteine catabolism and improved GSH synthesis.
    • The naturally occurring cysteine-rich proteins
      • Whey
      • Keratin [26]

Další regulace met. drah homocysteinu

  • Glycine methyltransferase
    • Stimulována adenosylmethioninem [6]
  • Adenosylhomocysteine
  • Liver has capacity to synthesize more adenosylmethionine
  • Only liver, kidney, pancreas, intestine and brain [6]

Hyperhomocysteinemie

  • Elevated plasma homocysteine concentrations are associated with common pregnancy complications and adverse outcomes, including preeclampsia, spontaneous abortion, placental abruption, and recurrent pregnancy loss [16]
  • Homocysteine toxicity may be mediated directly by S-adenosyl homocysteine (SAHcy)
    • SAHcy is a competitive product inhibitor of DNA methyl transferase and of histone methyl transferase [16]

Cholin

  • Major dietary source of methyl-groups
  • Choline's metabolites
  • Biosynthesis of cell membranes
  • Bioactive phospholipids
  • Neurotransmitter acetylcholine [7]
  • Endogenous de novo synthesis of phosphatidylcholine catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT) in the liver [7]
    • Estrogen induces expression of the PEMT gene and allows premenopausal women to make more of their needed choline endogenously [7]
    • Formed when methionine supplies a methyl group to ethanolamine [1]
  • Nutriční deficit cholinu
    • Adult men and postmenopausal women
      • Fatty liver
      • Liver or muscle cell damage
    • Reduces the capacity to handle a methionine load, resulting in elevated homocysteine [7]
  • Critical during fetal development
    • Alters DNA methylation
      • Influences neural precursor cell proliferation and apoptosis
        • Long term alterations in brain structure and function, specifically memory function [7]
  • Dietary intake of choline by the pregnant mother and later by the infant directly affects brain development and results in permanent changes in brain function. [10]
    • Choline deficiency during these sensitive periods results in memory and cognitive deficits that also persist [10]
  • Perinatal choline supplementation can reduce the behavioral effects of prenatal stress and the cognitive effects of prenatal alcohol exposure in offspring.
    • Choline involves DNA methylation, altered gene expression, and associated changes in stem cell proliferation and differentiation [10]

tetrahydrobiopterin (BH4)

  • Essential cofactor in monoamine neurotransmitter biosynthesis [3]
  • 5-MTHF stabilize, enhance production of BH4, or possibly act as a substitute of HB4 [3]
  • Depressed individuals with low serum folate also tend to not respond well to SSRI antidepressant drugs [3]
  • Folate may play a role in the hepatotoxic effects of ethanol [20]

Taurin

  • The most abundant free amino acid in the body
  • The end product of methionine metabolism [16]
  • Taurine deficiency
    • X development of the endocrine pancreas
    • Reversed by supplementing the low-protein diet with taurine [16]

B12 vitamin

  • Prevents demyelination of nerve tissue
  • Critical site of B12 function in nerve tissue is in the enzyme, methionine synthase
    • Requires S-adenosylmethionine

Nedostatek methioninu v organismu

Symptomy

  • Rats fed a diet devoid of Met lost weight, developed anemia, and suffered from liver dysfunction. Other reported effects of Met deficiency include bladder and kidney lesions [25]

Nemoci asociované s nižší hladinou methioninu

Lupus

  • Global DNA hypomethylation seen in lupus [2]
    • Histone deacetylase (HDAC) inhibitors v klin. zkoušení [2]
    • DNA demethylation inhibitors
      • MBD2 was recently proposed to be involved in demethylation in T cells in lupus and is, therefore, a candidate target [2]

Rozštěpy neurální trubice

  • Women with the lowest average daily dietary intake of methionine (>1580 mg/d) had a greater risk of carrying a fetus affected by NTD [16]

Dlouhověkost a snížené množství methioninu

  • Isocaloric methionine restriction
    • Decreases mtROS generation and oxidative stress in rodent tissues
    • Increases maximum longevity in rats and mice [4]
  • The mean intake of proteins (and thus methionine) of Western human populations is much higher than needed [4]
    • Nebo jde spíše také o poměr proteinů živočišný / rostlinný (méně methioninu a spíše alkalizující vliv na moč...) ?
  • methionine levels in tissue proteins negatively correlate with maximum longevity in mammals and birds [17]
  • Lowering of methionine levels
    • Decreasing the sensitivity of proteins to oxidative damage
    • Lowering of the rate of ROS generation at mitochondria [17]
  • Overexpression of Msr
    • Leads to a dramatic increase in the maximum life span [19]

Methionin, jeho množství a další asociované nemoci

Nádory

  • Epigenome of cancer cells is distinguished by aberration of DNA methylation patterns, which include both hypo- and hypermethylation and aberrant regulation of DNA methylation enzymes [18]
  • Many tumor suppressor genes are hypermethylated (CH3) and silenced. Silencing of tumor suppressors leads to uncontrolled growth.
  • In metastatic cancer however, prometastatic genes, which are normally methylated and are methylated in non-metastatic breast cancer, are demethylated and activated by demethylase.
  • DNMT1 inhibitors might be used to block tumor growth early in therapy and then replaced with DNA hypomethylation inhibitors in later stages when metastasis is a serious concern. [18]
    • Inhibition of DNA methylation by DNA methylation inhibitors might lead to activation of these genes DNMT: DNA methyltransferase. [18]
    • DNA methylation inhibitors are now being tested as potential anticancer agents [18]
  • Treatment with SAM, the methyl donor of the DNA methylation reaction
    • Could lead to hypermethylation
      • Inhibition of metastatic protein protease
      • Inhibition of cell invasion in vitro and in vivo [18]
  • SAM inhibits
    • Demethylase activity in HEK 293 cells
    • MBD2 demethylase activity in vitro [18]
  • SAM was shown to be chemoprotective against rat hepatocarcinogenesis
    • Involve DNA methylation [18]
  • SAM levels can prevent metastasis
    • Might some therapeutic and prophylactic potential in methyl-enriching diets [18]
  • Malignant cells fail to utilize homocysteine (HCYS) in place of methionine (MET) and they are dependent on exogenous MET for growth [19]
    • In animals, reduction of plasma MET to <5 microM = MET-stress
      • Dietary restriction of MET and administration of L-methionine-alpha-deamino-gamma-lyase (methioninase)
      • Inhibits the growth of brain tumor xenografts in athymic mice
      • Enhances the efficacy of DNA alkylating chemotherapeutic agents [19]
        • Marked inhibition of O6-methylguanine-DNA methyltransferase (MGMT) expression
        • Induction of cell cycle check points
        • Inhibition of pro-survival pathways by MET-stress [19]
      • Mutational variability determines the mode of death (mitotic catastrophe versus apoptosis) in tumor cells subjected to MET-stress [19]
  • Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. [22]
  • The development of methioninase which depletes circulating levels of methionine
    • May be another useful strategy in limiting cancer growth [22]

Diabetes

  • Protein and lean body mass catabolism in the obese, insulin-resistant, or T2DM state could also influence amino acid patterns in the blood. [23]
  • Plasma methionine levels were highly correlated with predisease BCAA concentrations in >2000 persons for which the latter metabolites were predictive of T2DM development [23]
  • Plasma cystine concentration significantly increased in T2DM participants compared to nondiabetics in a cohort of BMI- and age-matched obese African-American women [23]
  • Involved with BCAA catabolism (vyšší hladiny v krvi) [23]
  • Perturbation of phenylalanine and tyrosine metabolism in the insulin-resistant condition

Nadbytek methioninu v organismu

Stárnutí a oxidační stres

  • Protein carbonyls are mostly derived from lysine, arginine, proline and threonine residues under oxidative conditions. [24]
  • Methionine residues and cysteine residues - sensitive to oxidation by ROS
  • Reversible
  • Oxidation of methionine residues
    • R- and S-stereoisomers of methionine sulfoxide (MetO)
    • Most cells stereospecific methionine sulfoxide reductases (Msr's)
    • Thioredoxin-dependent reduction of MetO residues back to methionine residues [20]
  • MetO content of proteins increases with age
    • In a number of different aging models
      • Replicative senescence
      • Erythrocyte aging
      • Not in mouse tissues during aging [20]
  • Increase in the rate of ROS generation
  • Decrease in the antioxidant capacity
  • Decrease in proteolytic activities that preferentially degrade oxidized proteins
  • Decrease in the ability to convert MetO residues back to Met residues
    • Direct loss of Msr enzyme levels / activity (u mnoha stárnoucích organismů)
      • Mutacemi
    • Indirectly to a loss in the availability of the reducing equivalents
      • Thioredoxin
      • Thioredoxin reductase
      • NADPH generation [19]
  • Modulating protein activity and cellular function by methionine residue oxidation
    • Rozsáhlé signální a regulační funkce [28]

Oxidační stres v MTCH

  • Excessive dietary methionine also increases mtROS generation in rat liver [4]
  • Given in excess, it can interfere with the utilization of nitrogen from dispensable amino acids [15]
  • In male mice, Met adenosyltransferase (MAT) 1A knockout strains have very high Met levels, low SAM levels, 40% lower GSH levels, and are much more prone to oxidative stress and tumor formation in the liver compared to wild type male mice [25]

Proteazom

  • Ubiquitination of proteins
    • Three step mechanism to tag proteins with a polyubiquitin chain for the proteasome [28]
  • The proteasome is a regulated, barrel-shaped multi-enzyme complex
  • Functional decline of the proteasome activity in aging organisms
    • Increasing protein aggregation and cellular death [28]
  • A lot of age related diseases are closely connected to an inhibition of the proteasome and the formation of large protein aggregates
    • Skin aging
    • Atherosclerosis
    • Age-dependent macula degeneration
    • Cataract formation
    • Neurodegenerative diseases [28]

Adverse Effects suplementů s methioninem

  • Gastrointestinal distress can occur
    • Podání s jídlem
      • Alleviate this effect
      • Enhance efficacy [1]
  • Heinz-body hemolytic anemia in cats
  • methionine could, potentially, cause fetal acidosis [1]
  • methionine is known to exacerbate psychopathological symptoms in schizophrenic patients, there is no evidence of similar effects in healthy subjects. [14]
  • Intakes higher than 5 times normal resulted in elevated homocysteine levels [14]
  • 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. [14]
  • methionine (5 or 10 g/d) was given to patients as a treatment for rheumatoid polyarthritis (22). No serious adverse effects were reported, although nausea, vomiting, constipation, and halitosis were frequent. [15]
  • 100mg/kg denně po týdnu vedlo k elevaci homocysteinemie [15]
  • Jednorázový methionine - loading test
    • Dizziness being the most common symptom, which was attributed to the methionine [15]
    • Isolated sleepiness, nausea, polyuria, and decreased or increased blood pressure were also observed [15]
    • Transient complications
      • Impairing perception and vigilance
      • Does not have serious adverse effects on vasculature and may be considered safe [15]

Overdosage/Acute Toxicity

  • Toxic to kittens
  • 2 grams orally per day to mature cats
    • anorexia
    • Methemoglobinemia
    • Heinz body formation (with resultant hemolytic anemia)
    • Ataxia
    • Cyanosis
  • Metabolic acidosis
    • In combination with an acidifying diet may occur with overdoses [1]
  • 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. [14]
  • A significant increase in plasma homocysteine was seen only when the methionine intake was increased to 5 times the normal intake. [15]
    • 10-fold larger dose, given mistakenly, resulted in death [14]
  • Daily doses of 250 mg (i.e., 4 mg/kg per day) are only 25% of the daily requirement
    • Shown to be safe [15]
  • Single dose 100mg/kg/d does not cause any serious complications
  • Schizophrenia se může zhoršit [15]
  • Inborn errors of sulfur amino acid metabolism, such as hypermethioninemia. [15]
  • High levels of Met given orally or by i.p. injection to guinea pigs induced cholestatic liver damage with hepatic ATP depletion, inhibition of RNA synthesis, nuclear fragmentation as well as hypoglycemia, hypothermia, and eventual death [25]

Methionin a další složky stravy

  • Severe imbalance in the diet
    • 6% casein diet containing 5% methionine
    • Endocrine mechanisms involving estrogen and progesterone appear to block reproduction [16]
  • Feeding low-protein diets s vyšším podílem methioninu throughout gestation
    • Increases in the global methylation of DNA in some of the fetal organs
      • Perturbation of SAM levels [16]
    • Offspring that remain smaller for the rest of their postnatal life [16]
    • The offspring of these animals went on to exhibit increased blood pressure in adult life [16]
    • Supplementing the low-protein diet with additional glycine can reverse the increase in blood pressure [16]
      • It appears that additional glycine improves vascular function of both dam and offspring.
        • Dam fed a glycine-supplemented diet is better able to adapt its vasculature to the demands of pregnancy
        • Protecting the fetus from abnormal programming caused by a restriction in the uterine blood supply [16]
  • Diets containing excess methionine may
    • Increase glucocorticoids
    • Change levels of progesterone [16]
  • Rozštěpy neurální trubice
    • Other components of the methionine cycle also influence the NTD risk, which was lowest for women whose diets were rich in choline, betaine, and methionine [16]
  • 80% methionine restriction substituting it for l-glutamate in the diet also decreases MitROS generation in rat liver [17]

Metabolismus glycinu ovlivněn methioninem

  • Urinary excretion of 5-l-oxoproline, a marker of glycine availability
    • Significantly lower when the diets contained
    • Significant correlation
      • Excretion of 5-l-oxoproline and excretion of sulfate
    • Glycine was consumed to detoxify the excess methionine
      • Availability of glycine for other metabolic processes became limiting [15]
  • The catabolism of unused methionine increases the demand for glycine and may cause a deficiency [16]
  • Any excess amino acids derived from the diet have to be diverted into catabolic pathways.
    • Glycine and serine are required for the catabolism of excess dietary methionine
      • Imbalance in the diet may lead to an unexpected deficiency. [16]
        • Especially during gestation !! [16]
          • Pregnant animal the demand for glycine during pregnancy may already exceed the capacity for its synthesis, making it conditionally indispensable [16]

Využívání suplementů s methioninem


urine acidification effects

  • Used in samll animals
  • Terapie a prevence např. močových konkrementů typu struvit [1]
    • Struvite dissolution therapy [1]
    • Sulfate from methionine is excreted in the urine as sulfuric acid [1]
  • Methionine has also been given to induce acidosis [15]
    • Metabolic acidosis has been shown to result in an inhibition of muscle protein synthesis in animals [15]
    • In human volunteers, acidosis resulted in negative nitrogen balance and decreased synthesis of muscle protein and serum albumin, which could be detrimental to body protein homeostasis if continued. [15]

Potlačení amoniakálního pachu moči

  • To reduce urine ammonia (pH) and odor in humans [1]
    • The acidosis induced by methionine could be the rationale for the prevention of recurrent urinary tract infections by l-methionine [15]

Nutritional supplement

  • In swine and poultry [1]

Laminitis

  • In horses and cattle [1]
  • Provides a disulfide bond substrate to maintain the hoof-pedal bone bond
  • Definitive studies demonstrating its effectiveness for this indication are lacking [1]

Treatment of ketosis

  • In cattle [1]

A “methionine-loading test” k predikci indiv. rizik KV chorob

  • Given orally usually 100 mg/kg body weight
    • Cca 7 times the average daily requirement for total sulfur amino acids (methionine plus cysteine)
  • Increase in plasma homocysteine concentration used as an index of the susceptibility of the individual to cardiovascular disease
  • This is believed to be a more sensitive index than the fasting homocysteine concentration alone [15]
  • In healthy volunteers, plasma homocysteine
    • Doubled at 2 h after methionine ingestion
    • Further increase at 4 h
    • Fell at 2 h, with a further fall at 4 h
  • Physiological increments in plasma homocysteine resulting from the intake of graded amounts of methionine, or of animal protein, induced endothelial dysfunction [15]

Osteoartritida - S-adenosylmethionine (SAMe)

  • SAMe - produced in the liver from methionine
  • Increase chondrocytes and cartilage thickness
  • May also decrease cytokine-induced chondrocyte damage [5]

A review and meta-analysis conducted by the Agency for Healthcare Research and Quality

  • Several randomized clinical trials
    • SAMe is more effective than placebo
    • Comparable to NSAIDs in reducing osteoarthritis pain
  • SAMe 1,2 mg per day X Celebrex 200 mg per day
    • Celecoxib much more effective in reducing pain during the first month of treatment
    • After two months of use, no difference in pain relief [4]
  • SAMe appears to be safe and better-tolerated than NSAIDs [4]

Nežádoucí účinky SAMe

  • SAMe increases serotonin turnover
  • May increase norepinephrine and dopamine levels
    • Anxiety, headache, insomnia, and nervousness
    • Hypomania and mania in patients with depression who took SAMe
  • Interact with other serotoninergic drugs
    • Antidepressants
    • Tramadol (Ultram)
    • Meperidine (Demerol) [4]

Cena

  • One-month supply typically costs $60 - $120 = comparable to the cost of celecoxib

Skladování

  • SAMe is an unstable compound
    • Product quality is another concern
    • Products on store shelves may contain little or none of the active ingredient !!!
      • SAMe may not be a reliable alternative treatment option
  • Butanedisulfonate salt formulation should be recommended
    • More stable [4]
    • Higher bioavailability [4]

Drug Interactions

AMINOGLYCOSIDES (gentamicin, amikacin, etc)

  • Aminoglykosidy jsou more effective in an alkaline medium
  • Urine acidification
    • Sníží efektivitu aminoglykosidů při terapii bacterial urinary tract infections [1]

ERYTHROMYCIN

  • More effective in an alkaline medium
  • Urine acidification sníží efektivitu terapie bacterial urinary tract infections [1]

QUINIDINE

  • Urine acidification may increase the renal excretion of quinidine [1]

Contraindications/Precautions/Warnings

  • Renal failure
  • Pancreatic disease
  • Hepatic insufficiency
    • Can cause increased production of mercaptan-like compounds
      • Intensify the signs of hepatic dementia or coma [1]
  • Preexisting acidosis
  • Urate calculi
  • Not recommended for use in kittens [1]


Literatura:

[1] KV Supply pharmacy. Methionine, Patient Information Sheet [Internet]. [citován 9. únor 2013]. Získáno z: www.kvsupply.com/kvvet/assets/html/METHIONINE.pdf
[2] Epigenetic therapeutics in autoimmu... [Clin Rev Allergy Immunol. 2010] - PubMed - NCBI [Internet]. [citován 9. únor 2013]. Získáno z: www.ncbi.nlm.nih.gov/pubmed/19644776
[3] The methylation, neurotransmitter, and antiox... [Altern Med Rev. 2008] - PubMed - NCBI [Internet]. [citován 9. únor 2013]. Získáno z: www.ncbi.nlm.nih.gov/pubmed/18950248
[4] Lowered methionine ingestion as respons... [Biochim Biophys Acta. 2008] - PubMed - NCBI [Internet]. [citován 9. únor 2013]. Získáno z: www.ncbi.nlm.nih.gov/pubmed/18252204
[5] Dietary Supplements for Osteoarthritis - January 15, 2008 - American Family Physician [Internet]. [citován 9. únor 2013]. Získáno z: www.aafp.org/afp/2008/0115/p177.html
[6] Metabolic regulatory properties of S-adeno... [Clin Chem Lab Med. 2007] - PubMed - NCBI [Internet]. [citován 9. únor 2013]. Získáno z: www.ncbi.nlm.nih.gov/pubmed/17963455
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