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SAMe
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S-adenosylmethionine, Ademetionine
- Methyl donor
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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 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).
Commonly Known As
- • SAMe
- • SAM-e
- • ademetionine
- • S-adenosylmethionine
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.
SAMe is typically used for the following health issues:
- • Anxiety
- • Depression
- • Fibromyalgia
- • Osteoarthritis
- • Cholestasis
- • Premenstrual syndrome (PMS)
SAMe is also said to enhance mental performance, boost liver health, slow the aging process, and help people quit smoking.
Health Benefits
Here's a look at some of the research on the possible benefits of SAMe.
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.
Depression
In a research review published in the Cochrane Database of Systematic Reviews in 2016, scientists analyzed 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."
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.
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
Side effects of SAMe are minor but include nausea and digestive issues. 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.
Interactions
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, medications 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.
Dosage and Preparation
SAMe supplements are sold as capsules, tablets, and powder. There is no recommended daily allowance for SAMe and no standard dose has been set.
What to Look For
When selecting a brand of supplements, look for products that have been certified by Consumer Labs, The U.S. Pharmacopeial Convention, or NSF International.
Look for SAMe supplements with an enteric coating, which helps protect the supplement from being released in the stomach, where stomach acid and enzymes can destroy the main ingredients. This allows the supplement to stay intact until it reaches the small intestine.
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S-adenosyl-methionine (SAMe) for Depressed Mood
SAMe is safe and can help treat depressed mood, research finds.
James Lake, MD. Integrative Mental Health Care
Posted Nov 20, 2018
As I write I am thinking of many of my own patients who find themselves struggling more as the days grow shorter. This post is about S-adenosyl-methionine (SAMe), a widely used natural supplement with an established track record for treating depressed mood.
How SAMe works to improve depressed mood
SAMe is a naturally occurring molecule in bacteria, plants, and animals and plays many important roles at the level of genes, immune function, and amino acid metabolism. In humans, SAMe is an important methyl donor, an essential step in the synthesis of several neurotransmitters from amino acids in the diet. The antidepressant effects of SAMe are probably related to multiple mechanisms of action including increased brain levels of serotonin, dopamine, and norepinephrine. The synthesis of these neurotransmitters by SAMe requires vitamin B12 and folate. Many depressed individuals are deficient in B vitamins, thus individuals taking SAMe for depressed mood will benefit from taking vitamin B12 and folate (especially in the form of l-methyl-folate) concurrently. In addition to the effects of SAMe on the above neurotransmitters, it has been suggested that antidepressant effects of SAMe are mediated by anti-inflammatory effects, changes in neuronal membrane fluidity, increased rate of serotonin turnover, inhibition of norepinephrine reuptake, and beneficial synergistic effects of SAMe on dopamine activity. Antidepressant effects of SAMe may also be mediated by anti-inflammatory effects and changes in neuronal cell membrane fluidity.
Research findings show efficacy comparable to antidepressants
SAMe has been widely used for decades to treat depressed mood and osteoarthritis in many European countries where it is available on a prescription basis in oral form, as an intramuscular injection, or for intravenous use. SAMe degrades rapidly when exposed to air and stable oral preparations posed manufacturing challenges for many years. Thus, many early studies investigated the antidepressant efficacy of SAMe administered intramuscularly or intravenously. Early studies reported that effective antidepressant doses of SAMe are significantly smaller when administered intravenously, and showed that few patients receiving SAMe intravenously had adverse effects.
In the U.S., SAMe is available in oral form only and can be purchased as an over-the-counter tablet in pharmacies and health food stores. Shelf-life can be prolonged by refrigeration and protecting SAMe from degradation in blister packs. e-counter supplement in pharmacies and health food stores. Oral SAMe is available in two different forms. Oral forms of SAMe are combined with other molecules to reduce the rate of oxidative degradation and extend shelf life. The butane-disulfonate is available as an enteric-coated tablet and may have significantly greater bioavailability and longer shelf life than the tosylate form.
The standard maintenance regimen of oral SAMe for depressed mood is between 800 and 1600 mg/day in two-to-four divided doses. A common strategy is to start SAMe at a dose of 200mg twice daily, and gradually increase to 400mg twice daily, monitoring for side effects and therapeutic response. Absorption is improved when SAMe is taken on an empty stomach (i.e., before meals).
Advantages of SAMe compared to prescription antidepressants
Most currently available antidepressants have a delayed onset of action, thus consistent improvement in mood may be noticeable only after four to six weeks of daily use. In contrast, SAMe has a relatively rapid onset of action, usually within one week of starting treatment. Another important advantage of SAMe is the absence of clinically significant interactions with prescription medications and relatively few side effects compared to antidepressants.
In addition to its mood enhancing effects, there is evidence that augmentation with SAMe (400mg) twice daily, in individuals who are not responding to antidepressant therapy, may improve memory and other cognitive problems that often accompany depressed mood (Levkovitz 2012).
SAMe enhances response to antidepressants
Meta-analyses of placebo-controlled studies support that SAMe when used as a monotherapy is as effective as many widely prescribed antidepressants (Hardy et al 2003; Sharma et al 2017). Studies published in peer-reviewed medical journals support that combining SAMe with an SSRI antidepressant or venlafaxine (a serotonin-norepinephrine reuptake inhibitor) improves overall response and may accelerate response rate equivalent to results achieved when augmenting an SSRI antidepressant with bupropion or venlafaxine. The mechanism of action by which SAMe augments the effects of widely used prescription antidepressants in cases in which a patient has become non-responsive, may involve re-externalizing neurotransmitter receptors that have been internalized by the nerve cell membrane during prolonged exposure to an antidepressant.
Findings of a landmark study published in the American Journal of Psychiatry provided "preliminary evidence that SAMe can be an effective, relatively well-tolerated, and safe adjunctive treatment strategy for SSRI non-responders diagnosed with major depressive disorder"(Papakostas 2010). Individuals included in the study continued on recommended doses of commonly prescribed antidepressants including paroxetine, citalopram, duloxetine and others, while also taking SAMe. The authors noted that significantly more patients treated with adjunctive SAMe experienced clinical improvement and remission compared to matched patients receiving a placebo. The significance of findings was limited by small study size (73 total patients), the short duration of the study (6 weeks), and failure to include a comparison group taking an antidepressant only.
Combining SAMe with an SSRI or other antidepressant is an integrative approach that improves outcomes while permitting a reduction in the dose of the conventional antidepressant by as much as 30%. The advantages of reducing the dose of a conventional antidepressant include fewer side effects and improved adherence to treatment. In addition to improving the efficacy of antidepressants, there is evidence that the adjunctive use of SAMe may reduce sexual side effects frequently caused by SSRIs and other antidepressants.
Safety issues
Although SAMe is well tolerated, transient anxiety, insomnia, gastrointestinal side effects, dry mouth, and dizziness have been reported. With continued treatment, most side effects resolve within days or a few weeks. Many studies (including those reviewed above) show that SAMe may be safely used in conjunction with antidepressants, but because SAMe affects serotonin synthesis, taking it together with another supplement or medication that increases CNS serotonin may cause serotonin syndrome, a potentially serious syndrome characterized by anxiety, agitation, and insomnia.Consult with your physician before taking SAMe together with an SSRI antidepressant or another medication that increases brain levels of serotonin. Rare cases of hypomania have been reported in patients diagnosed with Bipolar Disorder and it is advisable to avoid SAMe if you have been diagnosed with bipolar disorder.
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Supplementation of S-adenosylmethionine tends to be in the 600-1,200mg range over the course of a day, divided into two or three separated doses with meals. The higher dosage (1,200mg) tends to be used more often, with the lower dosage (600mg) being used to cut costs.
For S-adenosylmethionine to benefit osteoarthritis, it appears to require a few weeks or up to a month of continual usage for benefits to show. Benefits to depressive symptoms may be much more rapid.
Some body states appear to be associated with lower circulating levels of SAMe, including osteoarthritis and depression where SAMe appears to hold potent therapeutic potential; after a build-up period of 1-2 months, supplemental SAMe at 800-1600mg daily appears to be as potent as some pharmaceutical options for both osteoarthritis and depression and appears to enhance some anti-depressants. Although lower circulating levels of SAMe are also seen in diabetes, the benefits of SAMe and glucose control are not as well established as depression and osteoarthritis. *
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SAMe appears to be safe and might be effective in treating osteoarthritis and depression. However, SAMe might interact with use of antidepressants. Don't use SAMe and prescription antidepressants together.
Safety and side effects
Side effects from SAMe are rare and, if they occur, usually mild.
SAMe can cause:
- • Upset stomach
- • Nausea
- • Mild insomnia
- • Dizziness
- • Irritability
- • Anxiety
- • Sweating
- • Constipation
- • Diarrhea
If you have bipolar disorder, talk to your doctor before taking SAMe. The supplement might increase anxiety and mania.
If you have a compromised immune system, consider avoiding SAMe. People who have weakened immune systems are at risk of an infection caused by a specific microorganism. SAMe boosts this microorganism's growth.
Interactions
Possible interactions include:
- Antidepressants and other drugs and supplements that increase levels of serotonin. Don't take SAMe with antidepressants. The combination could cause effects similar to a condition caused by high levels of the chemical serotonin to accumulate in your body (serotonin syndrome).
- Antipsychotics. Be cautious when taking these drugs with SAMe. The combination could increase the risk of serotonin syndrome.
- Amphetamines. Be cautious when taking these drugs with SAMe. The combination could increase the risk of serotonin syndrome.
- Dextromethorphan. Taking SAMe with this cough suppressant could increase the risk of serotonin syndrome.
- Narcotics. Taking SAMe with meperidine (Demerol) or tramadol (Ultam, ConZip) could increase the risk of serotonin syndrome.
- St. John's wort. Be cautious when taking this supplement with SAMe. The combination could cause serotonin syndrome. *
2022-10-07