SAM, Part II

Last month, we discussed S-adenosyl-l-methionine (a.k.a. SAM) and focused on the studies where it has been used to treat patients with osteoarthritis. To review, SAM is a naturally occurring intermediate of methionine metabolism. It is a methyl donor and considered a sulfhydryl amino acid.

This month, our discussion will shift to a possible connection between SAM and homocysteine, along with two areas where SAM therapy has shown promise: fibromyalgia and depression.

In an interesting Swedish study,¹ researchers compared 18 healthy women to 12 women with chronic fatigue syndrome and/or fibromyalgia. They measured homocysteine in both groups. In the serum they did not find any differences, but when researchers looked at cerebrospinal fluid levels, they found that chronic fatigue syndrome patients and fibromyalgia patients had mean values of homocysteine that were triple that of controls.

Excessive homocysteine in the serum is metabolized in two ways:

1. methylation -- folic acid and vitamin B12 facilitate the donation and transfer of their methyl groups to homocysteine to reform methionine. The majority of homocysteine is metabolized this way.

    

2. transulfuration -- vitamin B6 helps convert homocysteine to cysteine.²

Elevated serum homocysteine was linked to the atherosclerotic process 30 years ago by Kilmer McCully, MD. Unfortunately, for decades Dr. McCully's findings were ignored by mainstream medicine. It was only recently that the medical community has acknowledged that Dr. McCully was not misguided, but in fact decades ahead of the rest of the world. In addition to atherosclerosis, homocysteine may be involved in neural tube defects, Down's syndrome and declining brain function.³ Now, we may be adding fibromyalgia and depression to this list.

The SAM Connection

So what role does S-adenosyl-methionine play in cerebrospinal fluid homocysteine levels? Researchers are not yet sure. When SAM donates methyl groups, it is converted to S-adenosyl-homocysteine ASH), which is a precursor to homocysteine. On the surface, it would appear that more SAM would mean more homocysteine, a situation we want to avoid. However, in the Swedish paper, the authors felt there may be a link in the SAM to ASH ratio, and when SAM levels are low, homocysteine may build up. The SAM to ASH ratio theory was proposed because the authors were aware of studies showing that administration of SAM helps patients with fibromyalgia and depression.

In 1991 Jacobsen, in a double-blind, placebo-controlled study, gave 800 mg of SAM orally to 44 fibromyalgia patients for six weeks. The results of the study showed that SAM administration produced mood elevations along with decreases in pain and fatigue.⁴

In a 1994 study, Grassetto and Varotto⁵ gave 800 mg of oral SAM along with a 200 mg intramuscular injection to 47 fibromyalgia patients over a six week period. At the end of the study, the authors used rating scales that showed a 40% reduction of tender point scores and a 35% reduction of depression scores. Measuring depression was included in both fibromyalgia studies, due to the fact that it often accompanies fibromyalgia.

In a study focusing on depression only, 80 post-menopausal women were given 600 mg of SAM in a double-blind, placebo-controlled, randomized trial with a washout. The results of the study showed that when SAM was given for 30 days, the level of depression decreased after 10 days of supplementation.⁶

Side Effects

SAM is generally very well tolerated in the vast majority of patients who use it. The most common side effects are nausea and other gastrointestinal symptoms. SAM is not recommended for people who suffer from bipolar disorders.

Conclusion

Having another weapon to use for both fibromyalgia and depression is exciting. I will be closely following the literature to see if there are any applications with SAM for chronic fatigue syndrome as well. I expect that with the renewed interest in SAM, scientists will figure out exactly how it works with patients who have fibromyalgia and depression, as well as how it affects homocysteine.

In the meantime, clinicians should make sure that fibromyalgia/chronic fatigue patients are receiving adequate amounts of the B complex, especially vitamin B12, folic acid, and vitamin B6.

Recommendations

The reason SAM has not been available was due to the high cost of manufacturing a stable, bioavailable product. Although SAM can now be purchased and is marketed by the Allergy Research Group in Hayward, California, the cost is still prohibitive. Based on the studies I have reviewed, I plan to try SAM in the following ways:

1. osteoarthritis patients who are not helped by glucosamine;
2. osteoarthritis patients who cannot tolerate glucosamine;
3. osteoarthritis patients who cannot tolerate nonsteroidal anti-inflammatories;
4. osteoarthritis patients who are concerned about long-term, nonsteroidal anti-inflammatory side effects; and
5. patients with fibromyalgia who are not responding well to their current regimens.

The dosing schedule I will attempt is as follows: For patients over 200 pounds I will dose 1200 mg per day in divided doses. For patients 150-175 pounds, the dose will be 1000 mg. For patients under 150 pounds, the dose will be 800 mg. I will try these amounts for a two-week period, since the literature indicates that people should notice the effects of SAM after one to two weeks of ingestion.

For those patients who feel better after two weeks, I will then reduce their daily dose of SAM by 200 mg and each week reduce SAM by 200 mg per day until the lowest dose that continues to give a benefit is achieved. I anticipate this number will probably be in the range of 400 to 800 mg per day. If a patient does not feel a difference after two weeks of therapy, I will discontinue SAM supplementation due to its high cost. I encourage clinicians who try SAM to share their results (positive or negative) with me.

References

1. Regland. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scandinavian Journal of Rheumatology 1997;26:301.

    

2. Andersen GD. Homocysteine. Dynamic Chiropractic March 23, 1998, p. 28.

    

3. Whitaker. Health and Healing August 1997;7(8):3.

    

4. Jacobsen, et al. Oral s-adenosyl-methionine in primary fibromyalgia. Double-blind clinical evaluation. Scandinavian Journal of Rheumatology 1991;20:294-302.

    

5. Grassetto and Varotto. Primary fibromyalgia is responsive to s-adenosyl-l-methionine. Current Therapeutic Research 1994;55:797-806.

    

6. Salmaggi, Bressa, et al. Double-blind, placebo-controlled study of s-adenosyl-l-methionine in depressed postmenopausal women. Psychotherapy and Psychosomatics 1993;59(1):34-40.