S-Adenosylmethionine

S-Adenosylmethionine (SAMe) is a molecule that is produced naturally in our body. It is essentially amino acid methionine attached to an ATP molecule; this molecule flows in the bloodstream naturally and acts as a 'methyl donor'. In chemistry, a methyl group is merely a carbon molecule (attached to some hydrogens), and contributing a methyl group to other molecules may speed up or maintain reactions in the body as a type of metabolic 'maintenance'. Choline is another important methyl donor in the body, but the two are not necessarily interchangeable due to selectivity of some reactions.

SAMe takes part in the formation, activation or breakdown of chemicals such as proteins, hormones, and phospholipids in the body. It plays a role in the immune system, preserves cell membranes, and helps form and break down chemicals in the brain, such as dopamine, serotonin, and melatonin. It works with vitamin B12 and vitamin B9 (folate).  Deficiency of either vitamin B12 or folate may decrease levels of SAMe in the body.

Since 1999 SAMe has been available as a dietary supplement in the United States. S-Adenosylmethionine is taken orally for anxiety, depression, fibromyalgia, heart disease, abdominal pain, bursitis, osteoarthritis, dementia, Alzheimer’s disease, chronic lower back pain, tendonitis, chronic fatigue syndrome (CFS), slowing aging process, liver disease, improving cognition, and Parkinson’s disease. SAMe is also used for treating multiple sclerosis, attention deficit-hyperactivity disorder (ADHD), seizures, spinal cord injury, lead poisoning, migraines, to break bilirubin (a chemical in the body), or to help with disorders akin to the accumulation of a chemical called porphyrin or its precursors.

 

What is SAMe used for?

Depression

Studies have shown that S-Adenosylmethionine treats mild-to-moderate depression more effectively than placebo, and is just as efficacious as antidepressant medicines without the side effects including headaches, sexual dysfunction and sleeplessness. Additionally, it appears that SAMe starts to work more quickly than antidepressants, which take 6-8 weeks to start working. While scientists aren’t sure how S-Adenosylmethionine works to alleviate depression, they hypothesize it might raise the amount of serotonin in the brain precisely as some antidepressant medications do.  

In many of the studies, injectable forms of SAMe was used instead of oral supplements. More studies are needed in order to determine if SAMe is effective for treating depression. Depression shouldn’t be taken lightly; a doctor’s advice should be taken before taking SAMe or any other supplement to treat depression. Fibromyalgia

Fibromyalgia is a medical condition characterized by widespread musculoskeletal pain accompanied by sleep, fatigue, mood, and memory issues. Scientists think fibromyalgia magnifies painful sensations by influencing the way our brain processes pain signals.

According to studies, SAMe can effectively reduce symptoms of fibromyalgia, including pain, morning stiffness, fatigue, and depressed mood. However, in most studies an injectable form of SAMe was used. Also, the studies that investigated oral doses of SAMe, some found the doses to be effective when taken by mouth while others found no usefulness.

 

Osteoarthritis

In a number of well-designed studies SAMe was found to decrease pain and inflammation in the joints. Various short-term studies, ranging from 4 to 12 weeks, found SAMe supplements to be as effective as NSAIDs, such as ibuprofen and naproxen, in adults with hip, knee, or spine osteoarthritis, in reducing morning stiffness, easing swelling and pain, advancing range of motion, and speeding up walking pace. In another study, researchers compared SAMe to an NSAID called colecoxib. They found that SAMe was as efficacious as colecoxib in easing pain over time. Researchers believe SAMe promotes cartilage repair.

 

Liver disease

Often SAMe cannot be synthesized in the bodies of people with liver disease. Preliminary studies have shown that SAMe may be an effective treatment for chronic liver disease caused by alcoholism or medications. A study investigating 123 participants (male and female) with alcoholic liver cirrhosis found that their survival rates improved after undergoing SAMe treatment for two years better than placebo, and the treatment also delayed the need for liver transplants. Other studies on people with liver disease showed that S-Adenosylmethionine may help normalize their levels of liver enzymes. Studies in mouse model also back findings that show SAMe protects against liver disease and may also reverse liver damage. These studies, however have been small in size and short in duration. Bigger studies with longer duration are needed to confirm these results.

 

Dementia

Preliminary study suggests that S-Adenosylmethionine may improve cognition. The study showed that the participants’ ability to recall information and remember words were improved after taking SAMe. The researchers hypothesize that SAMe acts on areas of the brain that control gene expression of beta amyloid proteins. Plaques formed by beta-amyloid proteins around the brain’s neurons is a hallmark of Alzheimer’s disease.

 

Cancer

Some studies indicate that SAMe can effectively impede cancer tumor cells.

 

Are there side effects associated with taking SAMe?

S-Adenosylmethionine appears to be a relatively safe drug.

Studies on patients with Parkinson’s disease showed that taking the drug L-dopa may lower SAMe levels in the body, contributing to depression and increase side effects of L-dopa. If you have Parkinson’s disease consult your doctor before taking SAMe.

High doses of oral S-Adenosylmethionine can cause symptoms like upset stomach, gas, constipation, diarrhea, dry mouth, anxiety, dizziness, headache, and skin rashes. The drug can also trigger an allergic reaction in some people.

If you are suffering from any medical condition, check with a healthcare professional before start using SAM-e supplements. S-Adenosylmethionine might not be safe for people with conditions such as diabetes, bipolar disorder, and Parkinson's disease. Because SAM-e can affect the blood vessels, stop using SAM-e two weeks prior to surgery.

 

Drug interactions

If you’re taking medications regularly, consult your physician before you start taking SAMe supplements. S-Adenosylmethionine could pose a risk when taken in combination with antidepressants or supplements like St. John's wort. Some prescription cough medicines, painkillers, and treatments for Parkinson’s disease and diabetes may cause side effects due to SAMe intake. Patients taking antidepressants Monoamine oxidase inhibitors (MAOIs) should consult with their doctor before taking SAMe.

 

Can you get SAM-e naturally from foods?

There are no natural food sources of SAM-e.

 

References

  1. Cantoni, GL (1952). "The Nature of the Active Methyl Donor Formed Enzymatically from L-Methionine and Adenosinetriphosphate". J Am Chem Soc. 74 (11): 2942–3. doi:10.1021/ja01131a519.
  2. Jump up^ Ding, Wei; Smulan, Lorissa J.; Hou, Nicole S.; Taubert, Stefan; Watts, Jennifer L.; Walker, Amy K. (2015-10-06). "s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways". Cell Metabolism. 22(4): 633–645. doi:10.1016/j.cmet.2015.07.013PMC 4598287PMID 26321661.
  3. Jump up^ Wang, X.; Oh, M. W.; Komatsu, S. (2016-06-01). "Characterization of S-adenosylmethionine synthetases in soybean under flooding and drought stresses". Biologia Plantarum. 60 (2): 269–278. doi:10.1007/s10535-016-0586-6ISSN 0006-3134.
  4. Jump up^ Finkelstein J, Martin J (2000). "Homocysteine". Int J Biochem Cell Biol. 32 (4): 385–9. doi:10.1016/S1357-2725(99)00138-7PMID 10762063.
  5. Jump up^ Födinger M, Hörl W, Sunder-Plassmann G (Jan–Feb 2000). "Molecular biology of 5,10-methylenetetrahydrofolate reductase". J Nephrol. 13 (1): 20–33. PMID 10720211.
  6. Jump up^ Goyette, P.; Sumner, J. S.; Milos, R.; Duncan, A. M.; Rosenblatt, D. S.; Matthews, R. G.; Rozen, R. (1994-06-01). "Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification". Nature Genetics. 7 (2): 195–200. doi:10.1038/ng0694-195ISSN 1061-4036PMID 7920641.
  7. Jump up^ Booker, SJ; Grove, TL (2010). "Mechanistic and functional versatility of radical SAM enzymes". F1000 biology reports. 2: 52. doi:10.3410/B2-52PMC 2996862PMID 21152342.
  8. Jump up to:a b Landgraf, Bradley J.; McCarthy, Erin L.; Booker, Squire J. (2016-06-13). "Radical S-Adenosylmethionine Enzymes in Human Health and Disease"http://dx.doi.org/10.1146/annurev-biochem-060713-035504doi:10.1146/annurev-biochem-060713-035504. Retrieved 2017-03-10. External link in |website= (help)
  9. Jump up^ Roje S (2006). "S-Adenosyl-L-methionine: beyond the universal methyl group donor". Phytochemistry67 (15): 1686–98. doi:10.1016/j.phytochem.2006.04.019PMID 16766004.
  10. Jump up^ Loenen W (2006). "S-adenosylmethionine: jack of all trades and master of everything?". Biochem Soc Trans. 34 (Pt 2): 330–3. doi:10.1042/BST20060330PMID 16545107.
  11. Jump up^ Chiang P, Gordon R, Tal J, Zeng G, Doctor B, Pardhasaradhi K, McCann P (1996). "S-Adenosylmethionine and methylation". FASEB J. 10 (4): 471–80. PMID 8647346.
  12. Fundukian, L., ed. The Gale Encyclopedia of Alternative Medicine, third edition, 2009.
  13. Memorial Sloan-Kettering Cancer Center web site: “About Herbs: SAM-e.”
  14. Agency for Healthcare Research and Quality web site: "S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease."
  15. Natural Medicines Comprehensive Database web site: “SAMe.”
  16. Natural Standard Patient Monograph: “SAMe.”
  17. https://www.webmd.com/vitamins-supplements/ingredientmono-786-same.aspx?activeingredientid=786&activeingredientname=same
  18. http://www.umm.edu/health/medical/altmed/supplement/sadenosylmethionine
  19. Alpert J E, Papakostas G, Mischoulon D, Worthington J J, Petersen T, Mahal Y, 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;24(6):661-4.
  20. Bottiglieri T. Folate, Vitamin B12, and S-Adenosylmethionine. Psychiatric Clinics of North America. W.B. Saunders Company. 2013:36(1).
  21. Chavez M. SAMe: S-Adenosylmethionine. Am J Health Syst Pharm. 2000;57(2):119-23.
  22. Delle Chiaie R, Pancheri P, Scapicchio P. 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. Am J Clin Nutr. 2002;76(5):1172S-6S.
  23. Dey A, Caro AA, Cederbaum AL. S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G91-103.
  24. Fetrow CW, Avila JR. Efficacy of the dietary supplement S-adenosyl-L-methionine. Ann Pharmacother. 2001;35(11):1414-25.
  25. Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis; an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther. 2009;31(12):2860-72.
  26. Li T, Yu G, Guo T, et al. The plasma S-adenosylmethionine level is associated with the severity of hepatitis B-related liver disease. Medicine. 2015;94(4):e489.
  27. Lieber CS. Hepatic, metabolic, and nutritional disorders of alcoholism: from pathogenesis to therapy. Crit Rev Clin Lab Sci. 2000;37(6):551-84.