7. Liver Disease And Gallstones
Because the liver has over 500 critical functions, from synthesizing compounds to removing contaminants, diseases that impair the liver’s ability to carry out these functions can be life-threatening.40 Without SAMe, liver cells are less efficient at performing vital detoxification reactions—but scientists found that cirrhosis patients have alterations in the pathway that produces SAMe.41
Insufficient SAMe levels are linked to various liver diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.42,43 In multiple studies, patients with various liver problems (including drug toxicity) responded well when administered SAMe, showing signs of improvement in liver function and in some cases restoration of normal liver function.5,44-46 In a trial of patients taking 1,600 milligrams of SAMe daily, scientists found that evidence of liver damage was greatly reduced, including decreased blood bilirubin levels.47
SAMe was shown to treat alcoholic liver disease by at least four mechanisms: increasing glutathione levels, repairing glutathione transport into mitochondria, reducing toxicity of inflammatory cytokines, and increasing DNA methylation.48 Furthermore, SAMe may help prevent liver disease by increasing gene expression within liver cells involved in alcohol metabolism, boosting alcohol elimination rate after binge drinking.49
SAMe could also help prevent gallstones in women. In a controlled study of women taking oral estrogen contraceptives, 600 milligrams of SAMe daily reduced bile cholesterol, suggesting SAMe may also prevent gallstones in women with increased estrogen levels.50
Since Life Extension® introduced SAMe to American consumers 17 years ago, it has become well-known for its potent antidepressant effects.1
However, decades of accumulating studies indicate that this remarkable natural compound promotes the synthesis and reactions of chemicals throughout the body that are critical to key functions such as gene expression and DNA repair.4,5
As a result, scientists have now demonstrated that SAMe is effective in safely preventing, treating, and/or reversing numerous diseases, including Alzheimer’s, Parkinson’s, fibromyalgia, inflammatory bowel disease, insomnia, osteoarthritis, liver disease—and even the root causes of aging itself!5,12,16,20,23,24-27,29-31,34,37-39,44-47
Although SAMe was a relatively expensive nutrient when first introduced to the US market, the cost of synthesizing pharmaceutical-quality SAMe has now been greatly reduced—making SAMe a more affordable addition to a well-rounded supplement regimen.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002 Nov;76(5):1158S-61S.
- Available at: http://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046983. Accessed January 15, 2014.
- Available at: http://www.nhiondemand.com/viewcontent.aspx?mgid=403. Accessed January 15, 2014.
- Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotrophic molecule.Am J Clin Nutr . 2002 Nov;76(5):1151S-7S.
- Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine.A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs. 1989 Sep;38(3):389-416.
- Sofia HJ, Chen G, Hetzler BG, Reyes-Spindola JF, Miller NE. Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods. Nucleic Acids Res. 2001 Mar 1;29(5):1097-106.
- Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem. 2012 Aug;23(8):853-9.
- Lu Sc. S-Adenosylmethionine. Cell Biology. Apr 2000;32(4):391-5.
- Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects—an introduction. Am J Clin Nutr. 2002;76(suppl):1148S-50S.
- Jackson MI, Lunøe K, Gabel-Jensen C, Gammelgaard B, Combs GF Jr. Metabolism of selenite to selenosugar and trimethylselenonium in vivo: tissue dependency and requirement for S-adenosylmethionine-dependent methylation. J Nutr Biochem. 2013 Dec;24(12):2023-30.
- Inoue-Choi M, Nelson HH, Robien K, et al. Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore. BMC Cancer. 2013;13:389.
- Cavallaro RA, Fuso A, Nicolia V, Scarpa S. S-adenosylmethionine prevents oxidative stress and modulates glutathione metabolism in TgCRND8 mice fed a B-vitamin deficient diet. J Alzheimers Dis. 2010;20(4):997-1002.
- Available at: http://www4.lu.se/cell-proliferation-group/research/the-role-of-the-polyamines-in-cell-cycle-control-and-program. Accessed January 17, 2014.
- Madeo F, Eisenberg T, Büttner S, Ruckenstuhl C, Kroemer G. Spermidine: a novel autophagy inducer and longevity elixir. Autophagy. 2010 Jan;6(1):160-2.
- Available at: http://dl.dropboxusercontent.com/u/4465273/ADI%20London%202012%20Abstracts%20Document.pdf. Accessed January 17, 2014.
- Bottiglieri T, Godfrey P, Flynn T, Carney MW, Toone BK, Reynolds EH. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry. 1990 Dec;53(12):1096-8.
- Morrison LD, Smith DD, Kish SJ. Brain S-adenosylmethionine levels are severely decreased in Alzheimer’s disease. J Neurochem. 1996 Sep;67(3):1328-31.
- Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs. 1994 Aug;48(2):137-52.
- Fuso A, Nicolia V, Ricceri L, et al. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Neurobiol Aging. 2012 Jul;33(7):1482.e1-16.
- Lee S, Lemere CA, Frost JL, Shea TB. Dietary supplementation with S-adenosyl methionine delayed amyloid-b and tau pathology in 3xTg-AD mice. J Alzheimers Dis. 2012;28(2):423-31.
- de Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol. Jun 2006;5(6):525-35.
- Available at: http://www.pdf.org/en/parkinson_statistics. Accessed January 17, 2014.
- Obeid R, Schadt A, Dillmann U, Kostopoulos P, Fassbender K, Herrmann W. Methylation status and neurodegenerative markers in Parkinson disease. Clin Chem. 2009 Oct;55(10):1852-60.
- De Silva V, El-Metwally A, Ernst E, Lewith G, Macfarlane GJ, Arthritis Research Campaign working group on complementary and alternative medicines. Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review. Rheumatology (Oxford). 2010 Jun;49(6):1063-8.
- Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol. 1991;20(4):294-302.
- Tavoni A, Vitali C, Bombardieri S, Pasero G. Evaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover study. Am J Med. Nov1987;83(5A):107-10.
- Ianniello A, Ostuni PA, Sfriso P, Menenghetti L, Zennaro A, Silvan Todesco S. S-adenosyl-L-methionine in Sjogren’s syndrome and fibromyalgia. Curr Ther Res Clin Exp (USA). 1994;55(6):699-706.
- Schmedes A, Nielsen JN, Hey H, Brandslund I. Low S-adenosylmethionine concentrations found in patients with severe inflammatory bowel disease. Clin Chem Lab Med. 2004;42(6):648-53.
- Oz HS, Chen TS, McClain CJ, de Villiers WJ. Antioxidants as novel therapy in a murine model of colitis. J Nutr Biochem. 2005 May;16(5):297-304.
- Krzystanek M, Pałasz A, Krzystanek E, Krupka-Matuszczyk I, Wiaderkiewicz R, Skowronek R. S-adenosyl L-methionine in CNS diseases. Psychiatr Pol. 2011 Nov-Dec;45(6):923-31.
- Buscemi N, Vandermeer B, Pandya R, et al. Melatonin for treatment of sleep disorders. Evidence Report/Technology Assessment (Summary). 2004 Nov;(108):1-7.
- Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM. Human melatonin production decreases with age. J. Pineal Res. 1986;3(4):379-88.
- Sandrock AW Jr, Leblanc GG, Wong DL, Ciaranello RD. Regulation of rat pineal hydroxyindole-O-methyltransferase: evidence of S-adenosylmethionine-mediated glucocorticoid control. J Neurochem. 1980 Sep;35(3):536-43.
- Anisimov VN, Popovich IG, Zabezhinski MA, Anisimov SV, Vesnushkin GM, Vinogradova IA. Melatonin as antioxidant, geroprotector and anticarcinogen. Biochimica et Biophysica Acta. 2006;1757(5-6):573-89.
- Available at: http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed January 17, 2014.
- Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract. 2002 May;51(5):425-30.
- Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med. 1987 Nov 20;83(5A):81-3.
- Glorioso S, Todesco S, Mazzi A, et al. Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res. 1985;5(1):39-49.
- Hosea Blewett HJ. Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis. Crit Rev Food Sci Nutr. 2008 May;48(5):458-63.
- Available at: http://www.nytimes.com/health/guides/disease/alcoholic-liver-disease/print.html. Accessed January 20, 2014.
- Look MP, Riezler R, Reichel C, et al. Is the increase in serum cystathionine levels in patients with liver cirrhosis a consequence of impaired homocysteine transsulfuration at the level of gamma-cystathionase? Scand J Gastroenterol. 2000 Aug;35(8):866-72.
- Wortham M, He L, Gyamfi M, Copple BL, Wan YJ. The transition from fatty liver to NASH associates with SAMe depletion in db/db mice fed a methionine choline-deficient diet. Dig Dis Sci. 2008 Oct;53(10):2761-74.
- Caballero F, Fernandez A, Matias N, et al. Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis: impact on mitochondrial S-adenosyl-L-methionine and glutathione. J Biol Chem. 2010 Jun 11;285(24):18528-36.
- Mato JM, Cámara J, Fernández de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999 Jun;30(6):1081-9.
- Chawla RK, Bonkovsky HL, Galambos JT. Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. Drugs. 1990;40 Suppl 3:98-110.
- Sukhanov DS. Antioxidant properties of remaxol, reamberin, and ademetionine in patients with drug-induced liver injury on the background of antituberculous therapy. Eksp Klin Farmakol. 2013;76(4):45-8.
- Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology. 1990 Jul;99(1):211-5.
- Purohit V, Russo D. Role of S-adenosyl-L-methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium. Alcohol. 2002 Jul;27(3):151-4.
- Bardag-Gorce F, Oliva J, Wong W, et al. S-adenosylmethionine decreases the peak blood alcohol levels 3h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver. Exp Mol Pathol. 2010 Dec;89(3):217-21.
- Di PC, Tritapepe R, Di PF, Frezza M, Stramentinoli G. S-adenosyl-L-methionine antagonizes oral contraceptive-induced bile cholesterol supersaturation in healthy women: preliminary report of a controlled randomized trial. Am J Gastroenterol. 1984 Dec;79(12):941-4.
- Available at: http://www.cdc.gov/features/dsdepression/. Accessed January 17, 2014.
- Fava M. Switching treatments for complicated depression. J Clin Psychiatry. 2010 Feb;71(2):e04.
- Gueorguieva R, Mallinckrodt C, Krystal JH. Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses. Arch Gen Psychiatry. 2011 Dec;68(12):1227-37.
- Salmaggi P, Bressa GM, Nicchia G, Coniglio M, La Greca P, Le Grazie C. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom. 1993;59(1):34-40.
- Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Psychiatry Res. 1995 Apr 28;56(3):295-7.
- Alpert JE, Papakostas G, Mischoulon D, et al. S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol. 2004 Dec;24(6):661-4.
- Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010 Aug;167(8):942-8.