S-Adenosyl Methionine (SAM)

,Once SAM provides a methyl group, it becomes S-adenosylhomocysteine and then homocysteine. Homocysteine is now ready to be changed back into methionine which will once again be used to synthesize SAM. ( Homocysteine could also go into the transulfuration pathway too, but it is not shown here.)

As a Queen of the methylators, SAM does all the things a methylator does. Without enough of it you see all the diseases associated with poor methylation. So for a good understanding of how important SAM is, just read about methylation here.

Here are a few of the things SAM does.

• Needed for glutathione synthesis.
• Needed for stabalization of many proteins, including myelin, the nerve sheaths that are so important to proper nerve firing.
• Converts acetylserotonin to melatonin, which is necessary for a good nights sleep.
• Converts the neurotransmitter norepinephrine into epinephrine ( adrenaline)
• Converts guanidinoacetate into creatine
• Converts creatine into creatinine.
• Converts phosphatidylethanolamine into phosphatidylcholine
• Converts nucleotides to methylated nucleotides.
• Needed in the creation of CoQ10 and carnitine. These are all compounds essential to the work of the mitochondria, which is the energy power house in our cells.
• Involved in synthesis of methylcobalamin. Needed to also convert between various forms of B12.

Some varoius factoids about SAM

• Because of its essential role in reactions involving neurotransmitters, it’s not surprising that a lack of SAM plays a role in neurodegenerative conditions.
• If you are hypothyroid, you may not be making enough SAM. T4 is needed to convert riboflavin to FAD (flavin adenine dinucleotide) the active form of B
  (FAD) controls MTHFR which is needed to make methylfolate which produces SAMe
• Although SAM is the principle methyl donor in all cells of the body, SAM is mainly synthesized, utilized, and degraded in the liver. Up to 80% of liver methionine is converted to SAM, which is the source of glutathione, a principle antioxidant required for liver detoxificiation reactions (Bottiglieri,2002). Low SAM levels in the liver associated with the removal of liver tissue is a stimulus for liver tissue regeneration ( Lu,SC,2008).
• SAM has proven to be effective in the treatment of depression, with fewer side effects than is seen with conventional antidepressants (Chiaie,RD, 2002) and (Papakostas,2010). Nearly a third of severely depressed patients have folic acid deficiency accompanied by high plasma homocysteine (Bottiglieri, 2000).
• SAM is able to inactivate hormones such as estrogens (through methylation), supporting the use of methionine in conditions of estrogen excess. Its effects in preventing estrogen-induced cholestasis (stagnation of bile in the gall bladder) have been demonstrated in pregnant women and those on oral contraceptives. In addition to its role in promoting estrogen excretion, methionine has been shown to increase the membrane fluidity that is typically decreased by estrogens, thereby restoring several factors that promote bile flow.
• Methionine also promotes the flow of lipids to and from the liver in humans. Methionine is a major source of numerous sulfur-containing compounds, including the amino acids cysteine and taurine.
• SAM is necessary to make adequate levels of CoQ10. Clinically, CoQ10 has been used in the treatment of angina, heart failure, and after coronary artery bypass and cardiomyopathy, as well as inflammation and weakening of the heart muscle. The synthesis of CoQ10 requires components of the methylation pathway, in particular, adequate levels of SAM.
• SAM effects geme transcription. SAM methylates specific cytosines in DNA, and this regulates gene transcription. If cellular SAM is depleted, it leads to DNA hypomethylation
• Low SAM is Risk Factor for Alzheimer's Disease,

Supplementing SAM & Instability of Supplements

SAM can cause insomnia if not taken in the morning, and is best taken on an empty stomach.

S-adenosyl-l-methionine is chemically unstable, both in solution, and in dry state, and forms different degradation products. The chemical instability represents a problem during the preparation of therapeutic formulations. One research study showed the disaccharide trehalose exercises a protective effect towards the lyophilized SAM, decreasing its degradation (65% of SAM was detected after 50 days at 37 °C). A parallel study, performed to stabilize the SAM into lyophilized yeast cells enriched in the sulfonium compound, assessed the positive effect of trehalose also in whole cells, but in lesser measure. It is possible that using trehalose with SAM in the future will protect it and make it more shelf stable.What is currently done is to put it in an acid resistant capsule and the product is kept cool. It can’t be heat treated. SAM needs to be kept refrigerated. Best if it is in blister pack. Good SAM will usuallyl be more expensive than other SAM and this is why.