Symptoms of depression include:
- Persistent feelings of sadness or emptiness.
- Feelings of helplessness, hopelessness, guilt, and worthlessness.
- Loss of interest in pleasurable activities, including sex.
- Sleep disturbances.
- Fatigue. Loss of energy or enthusiasm. Difficulty in concentrating or making decisions. Ongoing physical symptoms, such as headaches or digestive disorders, that don't respond to treatment. Crying, tearfulness. Poor appetite with weight loss, or overeating and weight gain.
Over 150,000 Americans and many thousands of Europeans use SAM-E supplements regularly. SAM-E was discovered in Italy about 5 decades ago (Cantoni, 1952). However, the first clinical study of SAM-E's use for depression was not completed until the 1970s (Agnoli et al., 1976). At that time there were no usable oral preparations and early studies had to use intravenous [IV] and intramuscular [IM] delivery. SAM-E was first introduced into the U.S. dietary supplement market in 1999. It has been used with success to treat depression in Europe for the past 20 years. A discussion of SAM-E versus St-John's wort to treat depression can be found here.

As a methyl donor, SAM-E "donates" units called methyl groups, which contain hydrogen and carbon atoms, to other substances. This process is called methylation, and it is one way in which the body protects itself from damage on the cellular level.
SAM-E facilitates the manufacture of brain neurotransmitters
Methyl donors help to protect against cancer, heart disease, neurological disorders, and many age-related problems, and facilitate the manufacture of DNA and brain neurotransmitters. SAM-E is involved in more than 50 methylation reactions in the body, including the regulation of various hormones and neurotransmitters such as serotonin, melatonin, and dopamine.
Once SAM-E donates its methyl group to choline, creatine, carnitine, DNA, RNA, epinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). SAH donates its sulfur molecule to sulfur-containing amino acids such as cysteine, from which glutathione is formed. SAH then gives up its adenosine molecule to yield homocysteine. Homocysteine is a potentially toxic amino acid and an independent risk factor for coronary disease. Folic acid, choline, or betaine can change homocysteine back to methionine in the presence of vitamin B12, or convert homocysteine into cysteine and glutathione in the presence of vitamin B6. For this reason, it is recommended to supplement your diet with vitamin B12 and B6 when taking SAM-E.
SAM-E is particularly important for the liver because glutathione is synthesized from it. Glutathione is crucial for liver function. A good portion of liver SAM-E is turned into glutathione. Glutathione is the liver's natural antioxidant.
SAM-E has many other beneficial uses for several wide-ranging conditions.
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For best results it is recommended to also take TMG (trimethylglycine) 500mg-2000mg twice a day (which increases the metabolism of SAM-E), as well as co-factors such as folic acid up to 1mg/day, vitamin B6 up to 100mg/day, and vitamin B12 1mg/day.