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5 Benefits and Side Effects of SAM-e (Does Antidepression Really Work?)[Updated Feb/2023]

SAM-e (S-adenosylmethionine) is a common endogenous amino acid in the human body, mainly synthesized by methionine and adenosine triphosphate, which is indispensable for methylation, sulfhydryl transfer and aminopropylation, nucleic acids, proteins, The production and decomposition of phospholipids and amines are related to it.

Today, the medical community has found that SAMe may have a clinically significant impact on osteoarthritis, chronic liver disease, and depression, so it has become a hot research target.

What are the benefits of SAM-e in empirical medicine? Are there any side effects and contraindications? See text analysis for details


What are the recommended benefits of SAM-e?

  1. SAM-e is beneficial for depression

Major Depressive Disorder is a widespread and devastating disease that affects about 17% of the population and causes enormous personal suffering and economic losses.

The need for more effective and faster-acting antidepressants is highlighted by the significant limitations of currently available therapies (e.g., low response rates, resistance to treatment, high relapse rates, and delayed response weeks to months).

Only 1% of people with episodes of depression lasting 51 year would seek medical help, and only 42% of them received proper treatment.

A systematic review (8 randomized double-blind controlled trials with 1011 participants) noted that SAMe as monotherapy or in combination with antidepressants showed encouraging and generally positive results and was well tolerated. Note 1

The mechanism behind SAMe may be related to the enhancement of catecholamine methylation, increased serotonin turnover, inhibition of norepinephrine reuptake, enhanced dopamine activity, decreased prolactin secretion, and increased phosphatidylcholine conversion.

*Conclusion: For depression, the use of SAMe may confer positive help, but limited by small sample sizes, more research is needed to support this.

  1. SAM-e improves hot flushes

Hot flashes are the most common discomfort in menopausal women (prevalence of about 75%), the main symptoms are fever, accompanied by severe sweating, facial and chest redness, palpitations and anxiety, the episode lasts about 3 to 10 minutes, and a few may last for several hours.

In addition, some female breast cancer patients due to treatment-induced estrogen deficiency can also cause hot flashes, such as 60% to 70% of patients will experience hot flashes after using it moxifen (an anti-estrogen drug).

A single-arm phase II trial (7-week trial of 43 women with hot flashes) noted that oral SAM-e (400 mg twice daily) did not produce clinically significant improvement in hot flashes symptoms compared with placebo, and there was no difference in quality of life. Note 1

*Conclusion: According to current studies, there is no evidence that oral SAM-e can improve hot flashes

  1. SAM-e improves osteoarthritis

Osteoarthritis is a progressive degenerative disease with a lifetime prevalence of about 45%, especially among the elderly, where obesity is an aggravating risk factor and the risk of disease is doubled.

In addition to joint cartilage defects, osteoarthritis may be accompanied by subchondral bone sclerosis, bone spur formation, ligament laxity, weakening of the muscles around the joint, synovitis, etc., and patients usually have symptoms such as joint pain, stiffness, and limited movement. Note 4

A Cochrane Review (4 randomized controlled studies, 656 participants) noted that the use of SAMe (S-adenosylmethionine) for the improvement of osteoarthritis, although potentially clinically relevant, had little improvement in pain and function, and was therefore not recommended for routine care due to heterogeneity and bias between studies. Note 3

*Conclusions: Due to the lack of high-strength evidence, the improvement effect of SAMe on osteoarthritis is still inconclusive

  1. SAM-e improves fibromyalgia

Fibromyalgia is a chronic, generalized pain disorder characterized by pain and fatigue in parts of the body (muscles, tendons, and joints). In addition, sleep/cognitive/gastrointestinal dysfunction, depression, and anxiety may also occur.

As of now, the cause of fibromyalgia is unknown, but it may be related to genetic, neurological, psychological, sleep, and immune factors.

A double-blind controlled study (6 weeks, 44 people with fibromyalgia) suggested that oral SAM-e (800 mg) may be one of the treatment options compared with placebo for improving clinical disease activity, morning stiffness, pain, and mood assessment. Note 5

*Conclusion: Oral SAM-e may have a positive effect on vitamin myalgia, but more research is needed to validate it

  1. SAM-e is good for Liver cirrhosis

Cirrhosis is a common pathological phenomenon in the later stages of chronic liver disease (caused by hepatocellular degeneration necrosis, tissue fibrosis, and regenerated nodules), and common causes are mainly related to alcoholism, hepatitis B or C virus infection, and nonalcoholic fatty liver disease

A randomized, double-blind controlled trial (2-year trial of 123 patients with alcoholic cirrhosis) showed that oral SAMe (S-adenosylmethionine) improved overall survival and reduced liver transplant events compared with placebo, particularly in patients with unadvanced liver disease. Note 6

*Conclusion: Oral SAM-e may be helpful in improving liver disease, but more large empirical confirmation is needed

Are there any side effects of oral SAM-e?

In general, SAMe is safe to use in moderation, but possible side effects that have been reported include: nausea, vomiting, constipation, dry mouth, headache, dizziness, exhaust, diarrhea, anxiety, agitation, palpitations, mild insomnia, loss of appetite, sweating, nervousness, etc., especially when using high doses.

Safety precautions

  1. Do not use for pregnant or breastfeeding women (because the relevant safety is unknown)
  2. Do not use by children (due to unknown safety)
  3. Do not use for patients with bipolar disorder, immunocompromised immune function, Parkinson’s disease, Lesch-Nyhan Syndrome related diseases, it may aggravate the condition
  4. Do not use with antidepressants or drugs that affect neurotransmitters, which may increase the incidence of Serotonin Syndrome, causing restlessness, increased heart rate, high blood pressure, dilated pupils, muscle stiffness, and excessive sweating. , Common drug names are: fluoxetine, paroxetine, sertraline, amitriptyline, clomipramine, imipramine, phenelzine, tranylcypromine, Dextromethorphan, Meperidine, Pentazocine, Tramadol, St. John’s Wort Grass), L-tryptophan (L-tryptophan)
  5. Do not use with Parkinson’s disease drugs: Levodopa drugs, because SAMe may affect drug efficacy
  6. Do not use it with hypoglycemic drugs, because SAM-e may have a hypoglycemic effect and may cause hypoglycemia
  7. Stop taking SAM-e at least 2 weeks before the scheduled operation (because it may affect the central nervous system)
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