Table of Contents
Table of Contents
S-Adenosylmethionine, or SAMe, is a combination of the essential amino acid L-methionine and adenosine triphosphate (ATP), the main “energy molecule” of the body.1
SAMe plays a vital role in brain chemistry. It is critical in the manufacture of the important brain chemicals known as neurotransmitters, including serotonin, dopamine, and norepinephrine, the key neurotransmitters that regulate mood and emotional balance.
Numerous double-blind, human clinical studies have found SAMe to be extremely helpful in supporting mood health.5-7 Supplementing with SAMe is believed to improve mood via its ability to:
The mood-boosting effects of SAMe are relatively fast-acting, with noticeable improvements generally appearing after only one to two weeks of use. SAMe is significantly faster than many other natural mood supplements. SAMe is also considered safe during pregnancy and lactation.
SAMe has also demonstrated impressive results in supporting joint health. A deficiency of SAMe in the joint tissue, just like a deficiency of glucosamine, leads to loss of the gel-like nature and shock-absorbing qualities of cartilage. As a result, cartilage degeneration can develop, leading to pain and decreased joint function.
SAMe has been studied in 21,524 subjects with poor joint health in detailed double-blind clinical trials. SAMe supplementation apparently stimulates cartilage production and repair, helping maintain joint flexibility and function. SAMe has demonstrated significant clinical improvements without side effects. This ability to improve structure and function without side effects is impressive given the well-known side effects associated with popular joint medications such as the non-steroidal anti-inflammatory drugs like Celebrex, ibuprofen, indomethacin, naproxen, and aspirin.8-10
Fibromyalgia is associated with chronic musculoskeletal pain, depression, and fatigue. SAMe has been shown in double-blind human clinical studies to produce excellent benefits in patients with fibromyalgia. Improvements are noted by a significant reduction in the number of trigger points and painful areas, and improvements in mood. SAMe appears to be a very important supplement in these patients.11,12
SAMe has been shown to be quite beneficial in supporting liver health. The benefits are related to its function as the major methyl donor in the liver and the promotion of detoxification reactions.
SAMe supports the liver and detoxification by increasing the production of glutathione, the body’s master antioxidant, which is particularly important in protecting liver cells.
Significant clinical research indicates SAMe supplementation can be beneficial in conditions involving liver stress, alcohol-related damage, and impaired detoxification pathways. SAMe is particularly useful in protecting the liver from damage and improving liver function in conditions associated with fatty infiltration of the liver or estrogen excess due to oral contraceptive use, pregnancy, and premenstrual syndrome.
SAMe is also beneficial in Gilbert's syndrome, a common syndrome characterized by a chronically elevated serum bilirubin level (1.2 to 3.0 mg/dL). SAMe supplementation significantly decreases serum bilirubin in patients with Gilbert's syndrome.13,14
Beyond its effects on mood, SAM-e is crucial for overall cognitive function and memory.
It helps build and maintain healthy brain cell membranes by producing essential fats, like phospholipids. These healthy membranes are vital for ensuring brain cells can send and receive signals effectively, which is the foundation of learning and recall.1,15
SAMe is also critical in the manufacture of creatine and carnitine, two important compounds involved in cellular energy, critical to brain function. In fact, the manufacture of creatine in the body consumes roughly 40% of the methyl groups used as donors produced by endogenous SAMe.16 Hence, taking creatine as a dietary supplement may spare this tremendous load of responsibility of SAMe, thereby allowing it to donate its methyl group towards other biochemical reactions.
Preliminary evidence suggests SAMe may support focus, clarity, and memory, particularly in older adults. While more research is needed, SAMe shows promise as a neuroprotective compound that could help preserve brain health with age.17,18
About 30% of SAMe in the human body is found within mitochondria, the energy-producing compartment of cells.2 This high concentration is no accident. SAMe is critical to helping fuel mitochondrial function. Meaning it helps mitochondria produce the power that all cells need to function properly.
SAMe is essential for producing all sulfur-containing compounds in the body. This includes the master antioxidant glutathione, as well as key components of cartilage like glucosamine and chondroitin sulfate, which are vital for joint health.
Perhaps the most well-known function of SAMe is that, along with the active forms of folic acid and vitamin B12, it is critical to “methylation” reactions. Methylation is adding a single carbon unit (a methyl group) to another molecule. SAMe is often more effective in transferring methyl groups than other methyl donors. SAMe is the sole methyl donor involved in the proper methylation of our genetic material (DNA, RNA, and histones). As a result, it plays a huge role in cellular replication and the expression of the genetic code. SAMe-mediated methylation reactions are critical in the manufacture of many body components, especially brain chemicals, active forms of nutrients and enzymes, and those used in detoxification reactions. B12 and folic acid are involved in methylation reactions and the manufacture of SAMe, so a deficiency of these nutrients can lead to disturbances in SAMe function.3
Another aspect of SAMe methylation is its importance in autophagy. This process translates to “self-eating.” Autophagy is the cell’s quality control process to dispose of cellular garbage, debris, microorganisms, and unwanted compounds, as well as reuse those compounds that can be salvaged. Improved autophagy is associated with antiaging. In addition to improving the regulation of autophagy, SAMe is necessary for the metabolism of the nutrient spermidine, a key factor that enhances autophagy function.4
The bottom line is that the health effects of SAMe are far-reaching due to its central role in so many chemical reactions in the human body. Supplementation can provide insurance that enough SAMe is available to the body. Although the body makes SAMe on its own, levels can decline with age, chronic stress, poor nutrition, or certain medical conditions. When this happens, supplementation provides meaningful support.
Because SAMe can cause nausea and gastrointestinal disturbances in some people when it is first being used, it is recommended that a starting dosage of 200 mg twice daily be taken for the first three days, after which the dosage can be increased to 400 mg twice daily. On day 10, if necessary, the dosage can be increased up to 800 mg twice daily. After 3 weeks of use, the maintenance dosage for SAMe is 200 mg twice a day is recommended for long-term use.
For best results, take SAMe on an empty stomach for optimal absorption.
SAMe is considered safe during pregnancy and lactation. There are no known drug interactions with SAMe.
Most people notice benefits within 1–2 weeks, especially for mood support.
Morning is ideal, since SAMe can increase energy and alertness.
Yes, in fact, to enhance the benefits of SAMe, it is often combined with active forms of folate, B12, and B6. It can also be taken with glucosamine sulfate if being taken for joint health or any other dietary supplement. And taking creatine as a dietary supplement may help SAMe donate its methyl groups towards other biological functions.
Generally, side effects are rare or very mild. Mild side effects may include digestive upset, nausea, or restlessness, especially at higher doses. These are generally rare and improve with reducing the dosage.
SAMe is a powerful, versatile dietary supplement with benefits spanning mood, joint comfort, fibromyalgia, liver health, and cognitive and memory support. While the body produces it naturally, dietary supplementation can help restore optimal levels—particularly as we age or encounter health challenges.
If you’re considering SAMe, talk to your healthcare provider about the right dosage and whether it’s a good fit for your health goals.
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