S-Adenosylmethionine (SAMe) - A Very Important Natural Product

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S-Adenosylmethionine (SAMe) - A Very Important Natural Product

http://www.doctormurray.com/newsletter/2-9-2004.htm

 

S-Adenosylmethionine (SAMe) is a key physiological agent formed in the body by

combining the essential amino acid methionine to adenosyl-tri-phosphate (ATP).

SAMe was discovered in Italy in 1952. Not surprisingly, most of the research on

SAMe has been conducted in the country of its discovery.

 

Because SAMe is manufactured from methionine, one would think that dietary

sources of methionine would provide the same benefits as SAMe. However, high

doses of methionine have not been shown to increase levels of SAMe, nor does it

provide the same pharmacological activity as SAMe, and high dosages of

methionine are associated with some degree of toxicity.

 

Normally the body manufactures all the SAMe it needs from the amino acid

methionine. However, a deficiency of methionine, vitamin B12, or folic acid can

result in decreased SAMe synthesis. In addition, tissue levels of SAMe are

typically low the elderly and in patients suffering from osteoarthritis,

depression, and various liver disorders.

 

Pharmacology

 

SAMe is involved in over 40 biochemical reactions in the body. It functions

closely with folic acid and vitamin B12 in " methylation " reactions. Methylation

is the process of adding a single carbon unit (a methyl group) to another

molecule. SAMe is many times more effective in transferring methyl groups than

other methyl donors. Methylation reactions are critical in the manufacture of

many body components especially brain chemicals as well as in detoxification

reactions.

 

SAMe is also required in the manufacture of all sulfur-containing compounds in

the human body including glutathione (discussed below) and various

sulfur-containing cartilage components.

 

The beneficial effects of SAMe supplementation are far-reaching due to its

central role in so many metabolic processes.

 

Clinical Indications

 

There are five principle uses of SAMe: depression, osteoarthritis, fibromyalgia,

liver disorders, and migraine headaches.

 

Depression

 

SAMe is necessary in the manufacture of important brain compounds such as

neurotransmitters and phospholipids like phosphatidylcholine and

phosphatidylserine. Supplementing the diet with SAMe in depressed patients

results in increased levels of serotonin, dopamine, and phosphatidylserine, and

improved binding of neurotransmitters to receptor sites, resulting in increased

serotonin and dopamine activity and improved brain cell membrane fluidity

resulting in significant clinical improvement.

 

Based on results from a number of clinical studies it appears that SAMe is

perhaps the most effective natural antidepressant (although a strong argument

could be made for the extract of St. John's wort standardized to contain 0.3%

hypericin).

 

Several studies have compared SAMe to antidepressant drugs. These studies have

shown that SAMe is better tolerated and has a quicker onset. In one study

comparing SAMe to desipramine, at the end of the 4-week trial 62% of the

patients treated with SAMe and 50% of the patients treated with desipramine had

significantly improved. Regardless of the type of treatment, patients with a 50%

decrease in their Hamilton Depression Scale (HAM-D) score showed a significant

increase in plasma SAMe concentration. These results suggest that one of the

ways that tricyclic drugs exert antidepressive effects is by raising SAMe

levels.

 

Detailed clinical evaluations utilizing electroencephalograms (EEGs),

event-related potentials (ERPs) and low-resolution brain electromagnetic

tomography (LORETA) have clearly indicated a central nervous system

antidepressant action of SAMe.

 

Osteoarthritis

 

SAMe has also demonstrated impressive results in the treatment of

osteoarthritis. A deficiency of SAMe in the joint tissue, just like a deficiency

of glucosamine, leads to loss of the gel-like nature and shock absorbing

qualities of cartilage. As a result, osteoarthritis can develop.

 

In vitro studies have shown that SAMe exerts a number of effects that appear to

be highly relevant in the treatment of osteoarthritis. First of all, SAMe has

been shown to be very important in the manufacture of cartilage components. This

effect has been demonstrated very well in humans. In one double-blind study

conducted in Germany, the 14 patients with osteoarthritis of the hands that were

given SAMe demonstrated increased cartilage formation as determined by magnetic

resonance imaging (MRI). These results indicate SAMe is capable of producing

improvements in the structure and function of cartilage in joints affected by

osteoarthritis. In addition to this effect, SAMe has also demonstrated some mild

pain-relieving and anti-inflammatory effects in animal studies. All of these

effects combine to produce exceptional clinical benefits.

 

In double-blind trials, SAMe has demonstrated similar reductions in pain scores

and clinical symptoms to NSAIDS like ibuprofen, indomethacin, naproxen, and

piroxicam. What all of these studies indicate is that SAMe appears to offer

significant advantages over NSAIDs. While these drugs are associated with

significant risk of toxicity, side effects, and actual promotion of the disease

process in osteoarthritis, SAMe offers similar benefits without risk or side

effect.

 

Fibromyalgia

 

SAMe has been shown in four double-blind clinical studies to produce excellent

benefits in patients suffering from fibromyalgia. In one of the studies, SAMe

was compared to transcutaneous electrical nerve stimulation (TENS) - a popular

treatment for fibromyalgia - in 30 patients with fibromyalgia. Patients

receiving SAMe (200 mg by injection and 400 mg orally daily) demonstrated

significantly greater clinical benefit as noted by a decreased number of tender

points, subjective feelings of pain and fatigue, and improved mood. TENS offered

little benefit on most symptoms while SAMe was deemed " effective in relieving

the signs and symptoms of primary fibromyalgia. "

 

Liver Disorders

 

SAMe has been shown to be quite beneficial in several liver disorders including

cirrhosis, Gilbert's syndrome, and oral contraceptive-induced liver damage. Its

benefits are related to its function as the major methyl donor in the liver and

it's lipotropic activity. One of the leading contributors to impaired liver

function is diminished bile flow or cholestasis. SAMe is beneficial for a

variety of liver disorders because of its ability to promote bile flow and

relieve cholestasis.

 

One of the greatest risks of chronic liver diseases such as chronic hepatitis is

liver cancer. Supplementation with SAMe appears to be very much indicated in

these patients in the attempt to reduce the risk for liver cancer. Animal

studies have shown a significant protective effect for supplemental SAMe against

liver cancer in animals exposed to liver carcinogens.

 

Migraine

 

SAMe has also been shown to be of benefit in the treatment of migraine

headaches. The benefit arises gradually and long-term treatment is required for

therapeutic effectiveness.

 

Dosage

 

In general, the longer that SAMe is used the more beneficial the results. It is

perfectly suited for long-term use because of its excellent safety profile. The

typical dosage range is 100 to 200 mg twice daily.

 

No significant side effects have been reported with oral SAMe other than the

occasional nausea and gastrointestinal disturbances. However, individuals with

bipolar (manic) depression should not take SAMe unless under strict medical

supervision because SAMe's antidepressant activity may lead to the manic phase

in these individuals. This effect is exclusive to some individuals with bipolar

depression.

 

Interactions and Contraindications

 

SAMe functions very closely with vitamin B12, folic acid, vitamin B6 and choline

in methylation reactions. Because of SAMe's effects on the liver, it may enhance

the elimination of various drugs from the body. The clinical significance of

this effect has not been fully determined.

 

It has been cautioned that SAMe be avoided in patients Parkinson's disease.

Animal studies indicate that excessive methylation is associated with

Parkinson's disease and SAMe excess has caused Parkinson's disease-like effects

in animal studies. In addition, both animal and human studies indicate that

increased methylation can cause the depletion of dopamine and block the effects

of L-dopa. This line of research is contradicted, however, by preliminary

evidence that SAMe may improve the emotional depression and the impaired mental

function that is often associated with Parkinson's disease. Nonetheless, it is

recommended that patients with Parkinson's disease avoid supplementing with

SAMee until more is known.

 

 

 

Key References:

 

Stramentinoli G. Pharmacologic aspects of S-adenosylmethionine. Pharmacokinetics

and pharmacodynamics. Am J Med 1987;83(5A):35-42.

Bressa GM. S-adenosyl-l-methionine (SAMee) as antidepressant: Meta-analysis of

clinical studies. Acta Neurol Scand 1994;154(suppl):7-14.

Saletu B, Anderer P, Di Padova C, Assandri A, Saletu-Zyhlarz GM.

Electrophysiological neuroimaging of the central effects of

S-adenosyl-L-methionine by mapping of electroencephalograms and event-related

potentials and low-resolution brain electromagnetic tomography. Am J Clin Nutr

2002;76(5):1162S-71S.

Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of

S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract 2002;51(5):425-30.

Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in

primary fibromyalgia: double-blind clinical evaluation. Scand J Rheumatol

1991;20:294-302.

Di Benedetto P, Iona LG and Zidarich V: Clinical evaluation of

S-adenosyl-L-methionine versus transcutaneous nerve stimulation in primary

fibromyalgia. Curr Ther Res 53:222-9, 1993.

Avila MA, Garcia-Trevijano ER, Martinez-Chantar ML, et al. S-Adenosylmethionine

revisited: its essential role in the regulation of liver function. Alcohol

2002;27(3):163-7.

Cheng H, Gomes-Trolin C, Aquilonius SM, et al. Levels of L-methionine

S-adenosyltransferase activity in erythrocytes and concentrations of

S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with

Parkinson's disease. Exp Neurol 1997;145:580-5.

Charlton CG, Crowell B Jr. Parkinson's disease-like effects of

S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav

1992;43:423-31.

Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglieri T. S-Adenosyl-Methionine

improves depression in patients with Parkinson's disease in an open-label

clinical trial. Mov Disord 2000;15(6):1225-9.

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