SAM-e Benefits and Side Effects

SAM-e (S-adenosyl-L-methionine) is not an herb, vitamin, hormone, or dietary nutrient; it is a synthetic form of a chemical that is naturally produced by the human body. SAM-e exists in cells and is involved in a variety of essential biochemical processes, including cell maintenance and nerve function. It is considered to be a metabolite of the essential amino acid L-methionine. SAM-e is also known by many as ademetionine, S-adenosylmethione, SAM, and SAMe. Among the numerous supplements marketed, SAM-e is one of the few worthy of attention from researchers and consumers.

SAM-e supplements are marketed for use in connection with a variety of conditions including osteoarthritis, depression, fybromyalgia, and liver disease. Many individuals maintain that SAM-e is as effective for pain relief as aspirin, but does not produce the same side effects such as stomach irritation. It is also believed by some people to be more effective for relieveing depression than many common anti-depressants. Since SAM-e is not regulated by the FDA, it does not require a doctor's prescription. However, in other regions such as Europe, SAM-e is sold as a prescription drug for treating depression, arthritis, and liver disease.

SAM-e is normally produced in the liver from the amino acid methionine found in most healthy diets. Both folic acid and vitamin B12 are required for the synthesis of SAM-e, and deficiencies of either of these vitamins may result in low concentrations of SAM-e in the central nervous system. Lower than normal levels of SAM-e have been detected in individuals with liver cirrhosis, heart disease, Alzheimer's disease, and depression.

Suggested Benefits of SAM-e

While healthy people do not need to supplement with SAM-e researchers suggest that many people may benefit from this supplement. Suggested benefits of SAM-e supplementation include the following:
  • Osteoarthritis. A number of double-blind studies indicate that SAM-e may help individuals with osteoarthritis. Studies show that SAM-e may reduce stiffness, pain and swelling in arthritic joints, as well as improve overall joint health. Results of some studies even go as far as to suggest that SAMe may be as effective in some instances as ibuprofen and naproxen. However, there is no evidence that SAMe will be effective in any form of arthritis other than osteoarthritis.

  • Liver Cirrhosis. Preliminary research indicates that SAM-e may also be helpful for various liver conditions including cirrhosis. In one trial, people with liver cirrhosis caused by alcoholism who took SAM-e for two years experienced a nearly 50 lower death rate and/or liver transplantation rate, compared with study participant who received a placebo. The results of this trial, however, where not statistically significant. The results of similar trials conducted using people with less severe forms of cirrhosis has yielded more promising results.

  • Fibromyalgia. Preliminary research suggests that SAM-e may assist those with fibromyalgia. In one double-blind study in which people with fibromyalgia were given supplemental SAM-e showed beneficial effects, such as a decrease in fatigue, pain sensation, and stiffness. Study participants also noted a significant improvement in mood. Notwithstanding, not all studies have reported such beneficial results.

  • Depression. SAMe may be helpful for promoting mood and emotional well-being and has been used by some people for the treatment of depression. This has resulted in a series of preliminary studies using oral and parenteral SAMe to treat depression. While the results of these studies are promising they are still inconclusive.

Additional research suggests that SAM-e may also be helpful for cholestasis, liver injury due to alcohol, Gilbert's syndrome and migraines. It may also anti-depressant and hepatoprotective activities.

Again, early results supporting the health benefits of SAM-e are encouraging but not conclusive.

Possible Side Effects of SAM-e

Unlike many traditional antidepressants, SAMe has few reported side effects. It also has a rapid onset of action (usually only two weeks compared to the four week onset for standard antidepressants). A few people taking high doses have reported mild gastrointestinal upsets (such as stomach pain, diarrhea, nausea and flatulence), anxiety, insomnia, hyperactive muscle movement, and hypomania. However, many of these symptoms will diminish with time, with lower dosages, or when supplementation is stopped.

If you are suffering from severe depression, you should seek advice from a doctor before supplementing with SAM-e. It has also been reported that individuals with bipolar disorder should avoid SAM-e since it may bring on manic episodes.

Dosage and Administration of SAM-e

While there are no recommended doses of SAM-e researchers working with individuals suffering from various conditions have used the following amounts:
  • Osteoarthritis (Joint Health) - 800 to 1,200 mg a day
  • Depression - 400 to 1,600 mg a day
  • Fibromyalgia - 800 mg per day
  • Liver disorders - 1,200 mg per day
  • Migraine - 1,200 mg per day
Researchers have suggested taking supplemental B6, B12, folic acid and possibly trimethylglycine (particularly in people with elevated homocysteine levels) with SAM-e. These vitamins help metabolize homocysteine which, at elevated levels, may increase the risk of cardiovascular disease as well as a few other disorders.

Effects from SAM-e, if any, are usually evident within a few week of starting supplementation with SAMe.

Supporting Literature

Almasio P, Bortolini M, et al. Role of S-adenosyl-l-methionine in the treatment of intrahepatic cholestasis. Drugs. 1990; 40 (Suppl 3):111-123.
Angelico M, Gandin C, Nistri A, et al. Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 1994;54:459-464.
Bell KM, Plon L, Bunney Jr. WE, Potkin SG. S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry. 1988; 145:1110-1113.Bombardieri G, Milani A, Bernardi L, Rossi L. Effects of S-adenosyl-L-methionine (SAMe) in the treatment of Gilbert's syndrome. Curr Ther Res 1985;37:580-585.
Bottiglieri T, Godfrey P, et al. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neuro Neurosurg Psych. 1990; 53:1096-1098.
Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83(suppl 5A):66-71.
Chawla RK, Bonkovsky HL, Galambos JT. Biochemistry and pharmacology of S-adenosyl-l-methionine and rationale for its use in liver disease. Drugs. 1990; 40 (Suppl 3): 98-110.
Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosyl-methionine in the symptomatic treatment of intrahepatic cholestasis: a double-blind, placebo-controlled study. Gastroenterology 1990;99:211-205.
Glorioso S, Todesco S, Mazzi A, et al. Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985;5:39-49.
Harmand MF, Vilamitjana J, Maloche E, et al. Effects of S-adenosylmethionine on human articular chondrocyte differentiation: an in vitro study. Am J Med 1987;83(suppl 5A):48-54.
Jacobsen S, Danneskiold-Samsoe B, Bach Andersen R. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scan J Rheumatol. 1991; 20:294-302.
Kaye GL, Blake JC, Burroughs AK. Metabolism of exogenous S-adenosyl-L-methionine in patients with liver disease. Drugs. 1990; 40 (Suppl 3):124-128.
Konig B. Long-term (two year) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med. 1987; 83 (Suppl 5A):89-94.
Maccagno A. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83(suppl 5A):72-77.
Marcolongo R, Giordano N, Colombo B, et al. Double-blind multicentre study of the activity of s-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res 1985;37:82-94.
Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med. 1987; (Suppl 5A):81-83.
Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83(suppl 5A):78-80.