- If you live with a condition like osteoarthritis or depression, you may already know how it can affect other aspects of your health, contributing to issues like weight gain, difficulty sleeping, and chronic pain.
One remedy said to ease depression, arthritis, and other conditions is the supplement SAMe, also known as SAM-e, ademetionine, or S-adenosylmethionine. SAMe is the synthetic form of a compound that is produced naturally in the body from methionine (an essential amino acid) and adenosine triphosphate (an energy-producing compound).
SAMe isn't found naturally in food. The body typically makes what it needs for good health, however, some disease states and low levels of methionine, folate, or vitamin B12 are believed to contribute to low levels of SAMe.
It's thought that SAMe can help promote the production of chemicals known to play a key role in a variety of processes in the body, such as mood regulation, immune function, and pain perception.
Why Do People Take SAMe Supplements?
SAMe is typically used for the following health issues:
Premenstrual syndrome (PMS)
SAMe is also said to enhance mental performance, boost liver health, slow the ageing process, and help people quit smoking.
The Benefits: Can It Really Help?
Here's a look at some of the research on the possible benefits of SAMe.
1) Osteoarthritis: SAMe shows promise in the treatment of osteoarthritis of the knee or hip. It is said to relieve pain and have anti-inflammatory properties, and some research suggests that it may promote cartilage repair.
In a report published in the Cochrane Database of Systematic Reviews in 2009, researchers analysed four previously published clinical trials (with a total of 656 participants) and found that the use of SAMe may help reduce pain and improve function in people with osteoarthritis. Since the reviewed trials were of poor quality, however, the review's authors deemed these findings inconclusive.
2) Depression: In a research review published in the Cochrane Database of Systematic Reviews in 2016, scientists analysed eight previously published clinical trials comparing SAMe to the antidepressants imipramine, desipramine, or escitalopram, or a placebo.
SAMe was superior to a placebo when used with selective serotonin reuptake inhibitor (SSRI) antidepressants, but the evidence was considered low quality. Compared to imipramine, fewer participants experienced adverse effects when treated with an injectable form of SAMe. SAMe wasn't different from the placebo or antidepressants such as imipramine or escitalopram when used alone.
In their conclusion, the review's authors state that the use of SAMe for depression needs to be investigated further in larger and better-planned trials "given the absence of high-quality evidence and the inability to draw firm conclusions based on that evidence."
3) Fibromyalgia: In a research review published in the Journal of Complementary and Alternative Medicine in 2010, scientists looked at 70 previously published clinical trials evaluating the use of various types of complementary therapies for chronic fatigue syndrome and fibromyalgia. Along with magnesium, L-carnitine, acupuncture, and several types of meditation practice, the review's authors named SAMe among the therapies with the most potential for further research on their effectiveness against these conditions.
4) Liver Disease: SAMe may improve liver function in people with chronic liver disease, suggests a research review published in the journal PLoS One in 2015. However, in evaluating the 12 previously published clinical trials included in the review, the authors also found that SAMe may of limited benefit in the treatment of certain liver conditions such as viral hepatitis and cholestasis.
Possible Side Effects
SAMe may trigger a number of side effects, including anxiety, constipation, diarrhea, dry mouth, headache, heartburn, insomnia, gas, low blood sugar, nausea, nervousness, skin rash, and vomiting. Large amounts of SAMe may cause mania (an abnormally elevated mood). There's also some concern that the use of SAMe can trigger an allergic reaction in some people.
If you have bipolar disorder, Lesch-Nyhan syndrome, Parkinson's disease, or other health conditions, you should only use SAMe under the supervision of your healthcare provider as it may worsen symptoms.
It's important to note that there may be risks when combining SAMe with medication or other supplements. You shouldn't take SAMe in combination with antidepressants, cough medicine, diabetes medication, levodopa (L-dopa), L-tryptophan, medication that affects serotonin levels, St. John's wort, or other medication unless you are being monitored by a health professional. SAMe should be discontinued at least two weeks before a scheduled surgery.
The safety of SAMe in children, pregnant or nursing women, or people with kidney or liver disease hasn't been established. You can get tips on using supplements safely, but you should speak with your primary care provider before taking SAMe to discuss whether it's appropriate for you. Keep in mind that SAMe shouldn't be used as a substitute for standard treatment.
Source - VeryWell
And now the science bit
S-Adenosyl methionine[alternative names is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throughout the body, most SAM-e is produced and consumed in the liver. More than 40 methyl transfers from SAM-e are known, to various substrates such as nucleic acids, proteins, lipids and secondary metabolites. It is made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase. SAM was first discovered by Giulio Cantoni in 1952.
In bacteria, SAM-e is bound by the SAM riboswitch, which regulates genes involved in methionine or cysteine biosynthesis. In eukaryotic cells, SAM-e serves as a regulator of a variety of processes including DNA, tRNA, and rRNA methylation; immune response; amino acid metabolism; transsulfuration; and more. In plants, SAM-e is crucial to the biosynthesis of ethylene, an important plant hormone and signaling molecule.
The reactions that produce, consume, and regenerate SAM-e are called the SAM-e cycle. In the first step of this cycle, the SAM-dependent methylases that use SAM-e as a substrate produce S-adenosyl homocysteine as a product. S-Adenosyl homocysteine is a strong negative regulator of nearly all SAM-dependent methylases despite their biological diversity. This is hydrolysed to homocysteine and adenosine by S-adenosylhomocysteine hydrolase and the homocysteine recycled back to methionine through transfer of a methyl group from 5-methyltetrahydrofolate, by one of the two classes of methionine synthases (i.e. cobalamin-dependent or cobalamin-independent. This methionine can then be converted back to SAM-e, completing the cycle. In the rate-limiting step of the SAM cycle, MTHFR (methylenetetrahydrofolate reductase) irreversibly reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.
Radical SAM-e enzymes
A large number of iron-sulfur cluster-containing enzymes cleave SAM-e reductively to produce a 5′-deoxyadenosyl 5′-radical as an intermediate, and are called radical SAM enzymes. Most enzymes with this capability share a region of sequence homology that includes the motif CxxxCxxC or a close variant. The radical intermediate allows enzymes to perform a wide variety of unusual chemical reactions. Examples of radical SAM enzymes include spore photoproduct lyase, activases of pyruvate formate lyase and anaerobic sulfatases, lysine 2,3-aminomutase, and various enzymes of cofactor biosynthesis, peptide modification, metalloprotein cluster formation, tRNA modification, lipid metabolism, etc. Some radical SAM-e enzymes use a second SAM-e as a methyl donor. Radical SAM enzymes are much more abundant in anaerobic bacteria than in aerobic organisms. They can be found in all domains of life and are largely unexplored. A recent bioinformatics study concluded that this family of enzymes includes at least 114,000 sequences including 65 unique reactions.
Another major role of SAM-e is in polyamine biosynthesis. Here, SAM-e is decarboxylated by adenosylmethionine decarboxylase to form S-adenosylmethioninamine. This compound then donates its n-propylamine group in the biosynthesis of polyamines such as spermidine and spermine from putrescine.
SAM-e is required for cellular growth and repair. It is also involved in the biosynthesis of several hormones and neurotransmitters that affect mood, such as epinephrine. Methyltransferases are also responsible for the addition of methyl groups to the 2′ hydroxyls of the first and second nucleotides next to the 5′ cap in messenger RNA.
As of 2012 the evidence was inconclusive as to whether SAM can mitigate the pain of osteoarthritis; clinical trials that had been conducted were too small from which to generalize. A 2016 study concluded that for major depressive disorder, "Given the absence of high-quality evidence and the inability to draw firm conclusions based on that evidence, the use of SAMe for the treatment of depression in adults should be investigated further."
The SAM-e cycle has been closely tied to the liver since 1947 because people with alcoholic cirrhosis of the liver would accumulate large amounts of methionine in their blood. While multiple lines of evidence from laboratory tests on cells and animal models suggest that SAM might be useful to treat various liver diseases, as of 2012 SAM had not been studied in any large randomized placebo-controlled clinical trials that would allow an assessment of its efficacy and safety.
Oral SAM achieves peak plasma concentrations three to five hours after ingestion of an enteric-coated tablet (400–1000 mg). The half-life is about 100 minutes.
Gastrointestinal disorder, dyspepsia and anxiety can occur with SAM consumption. Long-term effects are unknown. SAM is a weak DNA-alkylating agent.
Another reported side effect of SAM is insomnia; therefore, the supplement is often taken in the morning. Other reports of mild side effects include lack of appetite, constipation, nausea, dry mouth, sweating, and anxiety/nervousness, but in placebo-controlled studies, these side effects occur at about the same incidence in the placebo groups.[medical citation needed]
SAM-e has recently been shown to play a role in epigenetic regulation. DNA methylation is a key regulator in epigenetic modification during mammalian cell development and differentiation. In mouse models, excess levels of SAM-e has been implicated in erroneous methylation patterns associated with diabetic neuropathy. SAM-e serves as the methyl donor in cytosine methylation, which is a key epigenetic regulatory process. Because of this impact on epigenetic regulation, SAM-e has been tested as an anti-cancer treatment. Cancer cell proliferation is dependent on having low levels of DNA methylation. In vitro addition has been shown to remethylate promoter sequences and decrease the production of proto-oncogenes.
Deficiencies in radical SAM-e enzymes have been associated with a variety of diseases including congenital heart disease, amyotrophic lateral sclerosis, and increased viral susceptibility.
Interactions and contraindications
Taking SAM at the same time as some drugs may increase the risk of serotonin syndrome, a potentially dangerous condition caused by having too much serotonin. These drugs include dextromethorphan (Robitussin), meperidine (Demerol), pentazocine (Talwin), and tramadol (Ultram). SAM may also interact with antidepressant medications increasing the potential for their side effects and reduce the effectiveness of levodopa for Parkinson's disease.[medical citation needed]
People who have bipolar disorder should not use SAM because it increases the risk of manic episodes.
Availability in different countries
In the United States and Canada, SAM is sold as a dietary supplement under the marketing name SAM-e (also spelled SAME or SAMe; pronounced "sam ee" or "Sammy"); it was introduced in the US in 1999, after the Dietary Supplement Health and Education Act was passed in 1994.
It was introduced as a prescription drug in Italy in 1979, in Spain in 1985, and in Germany in 1989; as of 2012, it was marketed as a prescription drug in Russia, India, China, Italy, Germany, Vietnam, and Mexico.
SAM-e, SAMe, SAM, S-adenosyl-L-methionine, AdoMet, ademetionine