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Clinical Studies
References
Methionine is a sulfur bearing essential amino acid important in hair, nail and muscle production, liver maintenance (lipotropic effects) and production of creatine and other aminos. Methionine may be beneficial for lowering urinary pH, liver disorders and improving wound healing. It may also be helpful in depression, alcoholism, allergies, pancreatitis, asthma, copper toxicity, radiation side effects, schizophrenia, drug withdrawal and Parkinson's disease.
Published Clinical Studiesclin
1
Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies.
Delle Chiaie R, Pancheri P, Scapicchio P.
III Clinica Psichiatrica La Sapienza University, Rome, Italy. delle.chiaie@flashnet.it
BACKGROUND: S-Adenosyl-L-methionine (SAMe), a natural compound, is the most important methyl donor in the central nervous system. In several clinical trials, SAMe showed antidepressant activity. OBJECTIVE: Two multicenter studies were conducted in patients with a diagnosis of major depressive episode [baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D) >or=18] to confirm the efficacy and safety of SAMe in the treatment of major depression. In the first study (MC3), 1600 mg SAMe/d was given orally; whereas, in the second study (MC4), 400 mg SAMe/d was given intramuscularly. In both studies, the effects of SAMe were compared with those of 150 mg imipramine/d given orally in a double-blind design. DESIGN: In MC3, 143 patients received oral SAMe and 138 patients received imipramine for 6 wk. In MC4, 147 patients received SAMe intramuscularly and 148 patients received imipramine for 4 wk. In both studies the 2 main efficacy measures were the final HAM-D score and the percentage of responders to Clinical Global Impression at the endpoint. Secondary efficacy measures were the endpoint Montgomery-Asberg Depression Rating Scale scores and the percentage of responders, responders being those patients showing a decrease in HAM-D score of >or=50% from baseline. RESULTS: In both studies, the results of SAMe and imipramine treatment did not differ significantly for any efficacy measure. However, significantly fewer adverse events were observed in the patients treated with SAMe. CONCLUSIONS: The antidepressive efficacy of 1600 mg SAMe/d orally and 400 mg SAMe/d intramuscularly is comparable with that of 150 mg imipramine/d orally, but SAMe is significantly better tolerated.
Publication Types:
PMID: 12418499 [PubMed - indexed for MEDLINE]
2
S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects.
Silveri MM, Parow AM, Villafuerte RA, Damico KE, Goren J, Stoll AL, Cohen BM, Renshaw PF.
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
BACKGROUND: S-adenosyl-L-methionine is an effective treatment for clinical depression, although the mechanism underlying this effect is unclear. Presently, in vivo phosphorus magnetic resonance spectroscopy (31P MRS) and brain transverse relaxometry were employed to test if S-adenosyl-L-methionine supplementation alters brain bioenergetics and/or transverse relaxation time (T2RT) in a nondepressed cohort. If these magnetic resonance techniques are sensitive to S-adenosyl-L-methionine induced alterations in neurochemical processes, these methods may be used in cases of clinical depression to elucidate the mechanism underlying the antidepressant effect of S-adenosyl-L-methionine. METHODS: Twelve subjects self-administered 1600 mg of oral S-adenosyl-L-methionine daily. Phosphorus spectra and transverse relaxation time were acquired at baseline and after treatment using a 1.5 Tesla scanner. RESULTS: Phosphocreatine levels were significantly higher after treatment, whereas beta nucleoside triphosphate levels, predominantly adenosine triphosphate in brain, were significantly lower after treatment. A surprising gender difference in T2RT emerged after supplementation, with women exhibiting significantly lower T2RT than men. CONCLUSIONS: Alterations in phosphocreatine and beta nucleoside triphosphate are consistent with the report that S-adenosyl-L-methionine is involved in the production of creatine, which in turn is phosphorylated to phosphocreatine using adenosine triphosphate. These findings suggest that S-adenosyl-L-methionine alters parameters associated with cerebral bioenergetic status and that some effects of S-adenosyl-L-methionine (T2RT) occur in a gender-specific manner.
Publication Types:
PMID: 14550683 [PubMed - indexed for MEDLINE]
Methionine potentiates both basal and GHRH-induced GH secretion in children.3
Bellone J, Farello G, Bartolotta E, Aimaretti G, Bellone S, Mucci M, De Matteis F, Ghigo E.
Division of Endocrinology, University of Turin, Italy.
OBJECTIVE: It is widely accepted that arginine is a potent GH secretagogue in man, probably acting via inhibition of hypothalamic somatostatin release. Although many other amino acids are known to stimulate GH secretion, their effects and mechanisms of action have not been extensively studied in humans. The aim of the present study was to clarify the effect, if any, of methionine (MET) on GH secretion in children with normal short stature (normal height velocity and IGF-1 > 100 micrograms/l). DESIGN: We studied the effect of MET (0.2 g/kg intravenously (i.v.) over 30 min) on both basal and GHRH (1 microgram/kg i.v. at 0 min)-induced GH secretion (group A) comparing its effect with that of arginine (ARG) at low and classical doses 0.2 and 0.5 g/kg i.v. over 30 min) (groups B and C). The effect of the combined administration of MET and ARG (0.5 g/kg i.v. over e0 min) (group D) on GH secretion was also studied. PATIENTS: Thirty-four children (20 male and 14 female, age 12.8-14.0 years), divided into four groups. MEASUREMENTS: Serum Gh was measured in duplicate by immunoradiometric assay. RESULTS: In group A, MET increased basal Gh levels (peak, mean +/- SEM 14.6 +/- 2.6 vs 2.6 +/- 0.6 mU/l; P < 0.01) and potentiated the GH response to 1 microgram/kg i.v. GHRH (78.0 +/- 17.6 vs 41.6 +/0 9.8 mU/I; P < 0.02). In group B, ARG (0.2 g/kg) increased basal GH levels (16.2 +/- 5.2 vs 2.4 +/- 0.6 mU/I; P < 0.03) and potentiated the GH response to GHRH (119.6 +/- 20.4 vs 48.8 +/- 14.2 mU/I; P < 0.01). In group C, ARG (0.5 g/kg) induced a clear GH rise (28.0 +/- 3.8 vs 2.0 +/- 0.6 mU/I; P < 0.001) and potentiated the GH response to GHRH (93.4 +/- 10.0 vs 34.2 +/- 4.6 mU/I; P < 0.001). The GH responses to MET and ARG alone in groups A and B were similar and lower than that to ARG in group C. The GH responses to MET or ARG combined with GHRH in groups A, B and C were similar. In group D MET failed to modify the GH response to 0.5 g/kg i.v. ARG (10.8 +/- 6.4 vs 9.6 +/- 6.0 mU/I). CONCLUSION: Methionine potentiates both basal and GHRH-induced Gh secretion in children as effectively as arginine. As methionine has no interaction with arginine, our data suggest that these amino acids act via a common mechanism.
Publication Types:
PMID: 9302373 [PubMed - indexed for MEDLINE]
Review article: Nutritional therapy in alcoholic liver disease.4
Stickel F, Hoehn B, Schuppan D, Seitz HK.
Department of Medicine I, University of Erlangen-Nuremberg, Germany.
Chronic alcohol consumption may lead to primary and secondary malnutrition. In particular, protein energy malnutrition not only aggravates alcoholic liver disease but also correlates with impaired liver function and increased mortality. Therefore, in these patients, adequate nutritional support should be implemented in order to improve their prognosis. Clinical trials addressing this issue have shown that nutritional therapy either enterally or parenterally improves various aspects of malnutrition, and there is increasing evidence that it may also improve survival. Therefore, malnourished alcoholics should be administered a diet rich in carbohydrate- and protein-derived calories preferentially via the oral or enteral route. Micronutrient deficiencies typically encountered in alcoholics, such as for thiamine and folate, require specific supplementation. Patients with hepatic encephalopathy may be treated with branched-chain amino acids in order to achieve a positive nitrogen balance. Fatty liver represents the early stage of alcoholic liver disease, which is usually reversible with abstinence. Metadoxine appears to improve fatty liver but confirmatory studies are necessary. S-adenosyl-L-methionine may be helpful for patients with severe alcoholic liver damage, since various mechanisms of alcohol-related hepatotoxicity are counteracted with this essential methyl group donor, while a recent large trial showed that the use of polyenylphosphatidylcholine is of limited efficacy.
Publication Types:
PMID: 12940921 [PubMed - indexed for MEDLINE]
The influence of folate and multivitamin use on the familial risk of colon cancer in women.5
Fuchs CS, Willett WC, Colditz GA, Hunter DJ, Stampfer MJ, Speizer FE, Giovannucci EL.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. Charles_Fuch@dfci.harvard.edu
Low intake of folate and methionine and heavy alcohol consumption have been associated with an increased overall risk of colon cancer, possibly related to their role in methylation pathways. We estimated the relative risk (RR) of colon cancer according to a history of colorectal cancer in a first-degree relative and categories of folate, methionine, and alcohol intake in a prospective cohort study of 88,758 women who completed family history and detailed food frequency questionnaires. During 16 years of follow-up, colon cancer was diagnosed in 535 women. The inverse association of folic acid with colon cancer risk was greater in women with a family history. Compared with women who consumed 200 microg or less of folic acid/day, the age-adjusted RR of colon cancer for those who consumed >400 microg/day was 0.81 (95% confidence interval, 0.62-1.07) in women without a family history of colorectal cancer and 0.48 (95% confidence interval, 0.28-0.83) in women with a family history (P for interaction = 0.02). The influence of family history was markedly diminished by use of multivitamins containing folic acid (P for interaction = 0.04). High levels of dietary methionine also reduced the effect of family history (P for interaction = 0.05), whereas moderate to heavy alcohol consumption increased the risk associated with family history (P for interaction = 0.004). Other risk factors for colorectal cancer did not significantly modify the influence of family history. Our results suggest that higher intake of folate and methionine, regular use of multivitamins containing folate, and avoidance of moderate to heavy alcohol consumption may diminish the excess risk of colon cancer associated with a family history of the disease.
PMID: 11895870 [PubMed - indexed for MEDLINE]
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