SAMe, happiness and serotonin

What exactly is SAMe?
SAMe is known popularly for its antidepressant effectiveness.
SAMe (S-adenosyl methionine) is derived from the essential amino acid methionine with the help of magnesium and ATP (our energy currency, produced in the mitochondria) and the enzyme MAT.
SAMe is the key methyl donor in the body.
Methylation is critical to body function. It is required in creation of creatine (which recycles ADP into ATP), and proper function of DNA, neurotransmitters, proteins, lipids, and enzymes; also, in creating glutathione (our most important antioxidant) and SAMe, in making serotonin more available, and in removing histamine and excess estrogen.
SAMe is fundamental to redressing undermethylated brain chemistry, which occurs in some 35% of bipolars, and is characterized by chronic severe depression.

Increasing serotonin in the synapse
As pointed out by Dr Walsh, methylation by SAMe or methionine reduces genetic expression of reuptake transporters that ferry serotonin out of  the synapse and back to the initial neuron. Decreased transporters mean that more serotonin accumulates in the synapse. The more the serotonin in the synapse, the more serotonin messages. Optimal serotonin makes us happy and content, and better able to handle stress.

Other Effects
SAMe also works on other consequences of undermethylation, such as:
fatigue, insomnia and low melatonin, oxidative stress, low glutathione
migraine, chronic pain, compulsions, addictions
metal toxicity, immune and liver issues, cirrhosis
low acetylcholine, phospholipids, and taurine
hormone dysregulation, excess estrogen

Intake
In the treatment for most depressed undermethylators (as indicated by high whole blood histamine and/or a low SAMe/SAH ratio), SAMe and/or methionine are introduced gradually until the correct level becomes evident. This is done in the context of the full range of treatments for undermethylation.

Warnings
Methylation is required for major brain and body functions. Thus, corresponding intake of SAMe and/or methionine for the undermethylated individual should support optimal health. However, if starting to feel too good, dosage should be backed down, in some cases stopped, to prevent hypomania or mania.
If already overmethylated (low blood histamine, high SAMe/SAH), and so, overstimulated (and prone to anxiety/panic; perhaps, hyperactivity, hypomania, mania, psychosis, paranoia or aggression), SAMe and methionine are entirely contraindicated (methylation does not need to increase further). SAMe/methionine are also contraindicated if taking SSRIs.

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the undermethylated (histadelic) subgroup, each person's biochemical requirements tend to be unique. So if you need treatment for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician. 

For a wider view of SAMe, undermethylation and bipolar disorder, you may want to see the 2018 edition of my book, Natural Healing for Bipolar Disorder
                available here.

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