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SAM-E

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S-adenosylmethionine (SAM, SAMe, AdoMet) is a naturally occuring chemical compound in the body, synthesized de novo from adenosine triphosphate (ATP) and amino acid methionine. It can be found in practically every tissue of the human body, and an especially large amount is present in the liver, and adrenal and pineal glands. It essentially acts as a co-substrate in the reactions of methylation and, as a methyl donor is crucial for the maintenance of other metabolic reactions as well as for homeostatic balance, or the balance of the body's internal environment. SAM takes part in the synthesis of hormones, nucleic acids, proteins, and neurotransmitters- such as norepinephrine, dopamine, and serotonin. A SAM deficiency in the brain leads to serious issues with its functioning, such as neuropathy, demyelinating diseases and calcification of the basal ganglia of the brain. Due to its characteristics, SAM is a safe, cheap and effective alternative to traditional antidepressants.1–3

Anti-depressant effects

Studies have shown that individuals with depression often have a low level of SAM in the tissues of their nervous system, especially in cerebrospinal fluid, and an improvement in mood typically correlates with higher SAM concentration. A similar relationship exists in the case of folic acid and vitamin B12 (cobalamin), which are co-factors of the methylation cycle - a four-coupled metabolic reaction to reproduce the S-adenosylmethionine after its previous use as a methyl donor. An inverse relationship was observed in the case of homocysteine formed during the demethylation of SAMe. Oral administration of SAM leads to a gradual normalization of its levels in cerebrospinal fluid, which demonstrates its ability of crossing the blood-brain barrier. The results of one of the larger clinical trials have shown that 400mg SAM given parenterally works just as effectively as 150 mg of imipramine- the first fully effective antidepressant. Similar results were obtained in many other studies, including those which used an oral dose of 1600 mg.2

Neurodegenerative diseases

As in the case of individuals with depression, low levels of SAM in the cerebrospinal fluid were observed in people with neurodegenerative diseases.1 Supplementing this compound prevented the loss of choline from the nervous system and increased the density of muscarinic acetylcholine receptors. Because of this, SAM has a positive effect on the functioning of the cholinergic system, and whose insufficiency directly leads to cognitive impairment in Alzheimer's disease.4–6

Joint pain and fibromyalgia

S-adenosylmethionine was also used to treat the symptoms of osteoarthritis, manifested by joint pain and limitation of motor function. Studies have shown that this supplement relieves arthritis pain as effectively as the clinically used celecoxib. Unlike steroid drugs whose effects are maintained at a constant level for their use and disappear after cessation of treatment, SAM does not bring immediate relief of pain but the intensity of its activity increases with the duration of treatment and lasts for up to a month after cessation.Additionally, SAM is effective in the treatment of fibromyalgia- a group of diseases of unknown etiology, characterized by generalized pain in the motor system, chronic feelings of fatigue, a feeling of stiffness and sleep disorders.8,9 The mechanism of action of SAMe in the treatment of rheumatic diseases has not yet been fully understood. The medical effect most likely results from the stimulation of proteoglycan production as well as its anti-inflammatory and analgesic effects.7–9

Liver protection

SAMe, as a source of the methyl group, is of particular importance for the proper functioning of the liver, which is the center of the body's metabolism. In a matter of weeks, a deficiency of this compound leads to progressive hepatic steatosis, and when this state continues for a long time, fatty passes steatohepatitis, which is a risk factor for cirrhosis and hepatocellular carcinoma. S-adenosylmethionine is involved in the synthesis of the universal in the plant and animal kingdom peptide antioxidant- glutathione. SAM's deficiency reduces the level of the tripeptide in hepatocytes and makes them more vulnerable to toxins, which the liver is supposed to neutralize.3 The results of large clinical trials have shown that SAMe supplementation for two years significantly increases the survival rate for transplantation in patients with liver cirrhosis.10

Dosage

The most commo daily dose is 1200mg, spread over 2-3 smaller doses. According to a guide to alternative medicine published on the website of the University of Maryland Medical Center, depending on the use of SAMe, recommends the following daily doses:

  •         Depression - 800-1600 mg distributed in two doses,
  •         Osteoarthritis - 800-1200 mg spread over 2-3 doses.
  •         Fibromyalgia - 400 mg twice daily for 6 weeks
  •         ALD - 600-1200 mg in several small doses for six months.

Synergy

Due to the fact that folic acid and vitamin B12 are involved in the recycling of S-adenosylmethionine, the simultaneous supplementation of these three compounds has a synergistic effect and can reduce a pharmacologically effective dose of SAMe.

Interaction

S-adenosylmethionine, like some antidepressants, increases the level of serotonin in the brain. Taking SAMe with depression medication (SSRI, iMAO) can lead to an overactivity of serotonin, which may lead to serotonin syndrome. This is characterized by headache, hallucinations, muscle stiffness, sleeplessness, racing thoughts, anxiety and symptoms of the gastrointestinal tract. Extreme cases of serotonin syndrome may lead to death. Substances containing SAM should not be used without first consulting a physician by people taking Prozac, paroxetine (Seroxat), sertraline (Zoloft), amitriptyline (Amitriptylinum), clomipramine (Anafranil), imipramine, phenelzine, and dextromethorphan (Acodin), pethidine (Demerol), and tramadol. In addition, S-adenosylmethionine may reduce the effectiveness of levodopa, used in the treatment of Parkinson's disease, and therefore should not be used by people taking this drug.2

Side effects

S-adenosylmethionine is considered safe for most people. Sometimes, especially in higher doses, SAMe can cause vomiting, diarrhea, constipation, dry mouth, headache, sleeplessness, loss of appetite, sweating, dizziness, and nervousness. It may also lead to a manic episode in people suffering from bipolar disorder.11

Bibliography

1. Morrison, L. D., Smith, D. D. & Kish, S. J. Brain S-Adenosylmethionine Levels Are Severely Decreased in Alzheimer ’ s Disease. J. Neurochem. 67, 1328–1331 (1996).
2. Papakostas, G. I., Alpert, J. E. & Fava, M. S-Adenosyl-Methionine in Depression: A Comprehensive Review of the Literature. Curr Psychiatry Rep. Dec; 5, 460–6 (2003). 
3. Mato, M. & Lu, S. C. Role of S-adenosyl-L-methionine in liver health and injury. Hepatology 45, 1306–1312 (2007).
4. Chan, A., Tchantchou, F., Graves, V., Rozen, R. & Shea, T. B. Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: critical role of S-adenosyl methionine. J. Nutr. Health Aging 12, 252–261 (2008).
5. Pavia, J., Martos, F., Glez-correa, J. A. & Garcia, A. J. Effect of S-adenosyl methionine on muscarinic receptors in young rats. Life Sci. 60, 825–832 (1997).
6. Williams, A. C. & Ramsden, D. B. Nicotinamide homeostasis : A xenobiotic pathway that is key to development and degenerative diseases. Med Hypotheses 65, 353–362 (2005).
7. Najm, W. I., Reinsch, S., Hoehler, F., Tobis, J. S. & Harvey, P. W. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. BMC Musculoskelet. Disord. 15, (2004).
8. H, V. et al. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheumatol. 26, 206–11 (1997).
9. S, J., B, D.-S. & RB, A. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol. 20, 294–302 (1991).
10. Mato, J. M. et al. S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J. Hepatol. 30, 1081–1089 (1999).
11. D., M. & M., F. Role of S-adenosyl-L-methionine in the treatment of depression: A review of the evidence. Am. J. Clin. Nutr. 76, 1158S–1161S (2002).
12.  http://nootropy.pl/2015/07/08/s-adenozylo-l-metionina-w-schorzeniach-oun/

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