Comprehensive Guide to S-Adenosylmethionine (SAM)

S-Adenosylmethionine (SAM)Dr. James Meschino DC, MS, ND
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General Features
S-Adenosylmethionine (SAM) is an important methyl donor (CH3) in the transmethylation reactions required for the synthesis of DNA bases, creatine, glutathione, neurotransmitters (i.e. melatonin), phosphatidylcholine, and for liver detoxification reactions.
In the body, SAM is synthesized from methionine and ATP. Methionine, required for the synthesis of SAM, is obtained from diet, or produced from homocysteine, which accepts a methyl group (CH3) from vitamin B12; that was transferred to vitamin B12 from folic acid originally. Thus the synthesis of methionine and SAM are primarily dependant upon an adequate nutritional status of folic acid and vitamin B12.1,2,3
Curiously, high doses of methionine do not increase levels of SAM, but rather are associated with some degree of toxicity.4 The most natural way to optimize endogenous synthesis of S-Adenosylmethionine is to ensure adequate intake of folic acid, vitamin B12 and protein.3 Of clinical significance is the fact that SAM supplementation on its own has been shown to provide significant results in depression, osteoarthritis, fibromyalgia and liver disorders.
Clinical Application and Mechanism of Action
1. Depression, Anxiety and Dementia
As a principle donor of methyl groups (CH3) to various reactions, SAM is necessary for the synthesis of phospholipids (phosphatidylcholine, phosphatidylserine) and neurotransmitters. SAM supplementation in depressed or anxious patients has resulted in increased levels of serotonin, dopamine and phosphatidylserine. It improves binding of neurotransmitters to receptor sites, and affects brain cell membrane fluidity, resulting in significant clinical improvement in depression and anxiety.2,3,6,7,8 A number of excellent clinical trials have demonstrated the value of SAM as a natural biochemical intervention in depression. The typical dosage is 400 mg, three to four times per day (studies include general depression and post-partum depression).9-13
Alzheimer’s disease patients have been shown to have low levels of SAM and may therefore, benefit from its administration.2,3
2. Osteoarthritis
SAM has demonstrated impressive results in the treatment of osteoarthritis. SAM is required for the synthesis of cartilage components and appears to exert pain-relieving and anti-inflammatory properties.14,15 At least 21,524 patients with osteoarthritis have participated in clinical trials using SAM supplementation. Even when tested against commonly used anti-inflammatory drugs (i.e. Advil, Motrin, Nuprin, Naproxen) SAM supplementation has provided significant relief of osteoarthritic symptoms and improved joint function and quality of life. An MRI (magnetic resonance imaging) study demonstrated increased cartilage formation in 14 patients with osteoarthritis of the hands, given SAM vs. the placebo. Unlike non-steroidal anti-inflammatory drugs SAM is not harmful to the intestinal tract, kidney or liver. In fact, it is used to support liver detoxification functions in anti-aging and certain diseases.16-24 In the above studies, the typical dosage of SAM was 400 mg, three times per day.
3. Fibromyalgia
Several clinical studies show that SAM can help improve various aspects of fibromyalgia, including a reduction in the number of trigger points, painful areas and improvements in mood. Other symptoms that may respond to SAM supplementation include morning stiffness and fatigue. Treatment doses were in the range of 800 mg of SAM per day.25,26,27
4. Liver Disorders
SAM is beneficial for a variety of liver disorders because of its ability to promote bile flow and relieve cholestasis. It has been used successfully in cirrhosis, Gilbert’s Syndrome, and oral contraceptive induced liver damage. Its benefits are directly attributable to its role as a major methyl donor in the liver (detoxification process) and its lipotropic activity (transporting fat out of the liver). In Gilbert’s Syndrome SAM at a dosage of 400 mg, three times daily has resulted in a significant decrease in serum bilirubin. In liver cirrhosis it has been shown to improve cell membrane function, improve bile flow and increase levels of glutathione; possibly the most important liver antioxidant and detoxification agent. Animal studies provide evidence of protection against liver cancers from SAM supplementation in animals exposed to liver carcinogens.28-38
In alcoholic cirrhosis, damage to the liver prevents the natural formation of SAM from the amino acid methionine. In a double-blind study, individuals with alcoholic cirrhosis of the liver who took SAM supplementation for two years had a 47% lower rate of death or need for liver transplantation, compared with those receiving the placebo. In patients with less severe cirrhosis, the results were even more impressive.39
5. Migraine Headaches
A long-term study revealed that SAM supplementation may be helpful in reducing the incidence of migraines in sensitive individuals.
For most conditions the therapeutic dosage range is typically 400 mg, two or three times daily. SAM can cause nausea and gastrointestinal disturbances in some people, thus, some patients may benefit from starting with 200 mg doses and working their way up to 400 mg per individual dose.5
1. Depression and Anxiety: 400 mg, three times per day
2. Osteoarthritis: 400 mg, two or three times per day
3. Fibromyalgia: 400 mg, two times per day
4. Liver Disorders: 400 mg, three times per day
5. Migraine Headache: 400 mg, two times per day (as a preventative intervention).
Adverse Side Effects, Toxicity and Contraindications
SAM should not be taken by individuals with bipolar (manic) depression, which may trigger a manic phase in these individuals. No other significant side effects have been reported with oral SAM supplementation other than occasional nausea and gastrointestinal disturbances
Drug-Nutrient Interactions
No known drug-nutrient interactions have been reported. However, as with folic acid, vitamin B12 and choline, SAM is a methyl donor, which may speed up the detoxification of various drugs in the liver.41 As well, SAM can affect neurotransmitter levels, caution should be exercised when using SAM in conjunction with anti-depressant and anti-anxiety medications. Excess serotonin production, for example, can lead to serotonin syndrome, characterized by myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing and rarely, rhabdomyloysis and death. This is true for all natural health products that can either increase the synthesis of serotonin or inhibit its degradation
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