Treating Depression With SAMe (Ademetionine)

If you live with a condition like 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 natural remedy to ease depression is the supplement SAMe, also known as ademetionine or S-adenosylmethionine.

What is SAMe?

SAMe (pronounced “Sammy”) stands for S-adenosyl-L-methionine. SAMe is a compound produced by the liver and used throughout the body in a chemical process called methylation. Methylation, essential to many chemical reactions in the body, is one of the last steps in the production of the brain chemicals serotonin, dopamine and norepinephrine (which regulate mood).

S-adenosyl-L-methionine (SAMe) is a compound made naturally by the body. An artificial form of the compound can also be made in a laboratory setting. In the late 1990s, the FDA approved artificial SAMe as a dietary supplement. In Europe, the compound has been a prescription drug since the 1970s. It is prescribed to treat a variety of conditions. It may help treat depression, osteoarthritis, heart disease, attention deficit-hyperactivity disorder (ADHD), and seizures.

SAMe is a compound made from two substances found in the body. The body uses it to make energy. SAMe has been used to ease pain in the joints and improve symptoms of depression. SAMe can be taken as a pill or powder. It can also be injected into the muscle or bloodstream by a healthcare provider.

SAMe supplements

S-adenosylmethionine is quite a mouthful; the abbreviation SAMe (pronounced samm-ee) is easier to say. Its chemical structure and name are derived from two materials you may have heard about already: methionine, a sulfur-containing amino acid; and adenosine triphosphate (ATP), the body’s main energy molecule.

SAMe was discovered in Italy in 1952. It was first investigated as a treatment for depression, but along the way it was accidentally noted to improve arthritis symptoms — a kind of positive side effect.

S-Adenosyl-L-Methionine or more commonly SAMe is an important biological agent in the human body and participates in detoxification reactions and in the manufacture of brain chemicals, antioxidants, joint tissue structures, and many other important components. It is normally produced in the liver from the amino acid methionine which is abundant in most diets as well. Folic acid and vitamin B12 are necessary for the synthesis of SAMe, and deficiencies of these vitamins results in low concentrations of SAMe (ademetionine) in the central nervous system. SAMe has been found to raise levels of the neurotransmitter dopamine, and patients may have to notice the effects in as soon as a week. Dopamine is an important chemical produced by the brain and responsible for mood.

Because there are no foods that have high SAMe levels, our bodies must make this substance. Our liver usually creates SAMe from the amino acid (protein) methionine, which is found in many foods. Interestingly, supplementing with methionine does not work as well as supplementing with SAMe, because creating SAMe takes multiple steps and requires many co-factors (other nutrients, such as vitamin B12, folate and others) to ensure that the process is successful.

SAMe depression

SAMe for the Treatment of Depression

Depression is a mood disorder in which people experience feelings of sadness, loneliness, and loss of interest for long periods of time. It is a fairly common condition in the United States. As many as 1 in 12 Americans from the age 12 and older report symptoms of depression, according to the Centers for Disease Control and Prevention (CDC).

Depression is a real — and common — medical illness that can affect your mind, body and spirit. It isn’t always easy to recognize, but depression has certain symptoms that are different from the “blues,” which everyone gets from time to time.

Depression can lead to many symptoms, some of which are:

  • unexplained pain
  • feeling worthless or guilty
  • thoughts of suicide or death
  • irrational reactions or angry outbursts
  • feeling sad, unhappy, or empty
  • difficulty concentrating or making decisions
  • difficulty sleeping, insomnia, or sleeping too much
  • loss of interest in normal activities
  • changes in appetite
  • anxiety or restlessness

SAMe’s effectiveness for depression stems from its key part in the physiological process known as methylation, which turns our biological switches on and off. According to a 2017 review of the research on SAMe published in the Journal of Clinical Psychiatry, methylation has been documented to be a factor in depression.

In a meta-analysis of the most significant clinical studies, SAMe efficacy was shown to exceed that of placebo and was equal to or slightly better than tricyclic antidepressants providing a rapid onset of action with few side effects. The first serious application of SAMe was for depression treatment, but as cases were evaluated it became evident that the compound was also helpful for anxiety, panic attacks, and other problems such as arthritis.

Major depression remains difficult to treat, despite the wide array of registered antidepressants available. In recent years there has been a surge in the popularity of natural or alternative medications. Despite this growing popularity, there is limited evidence for the effectiveness of many of these natural treatments. S-adenosyl-L-methionine (SAMe) is one of the better studied of the natural remedies. SAMe is a methyl donor and is involved in the synthesis of various neurotransmitters in the brain. Derived from the amino acid L-methionine through a metabolic pathway called the one-carbon cycle, SAMe has been postulated to have antidepressant properties.

Often an elevation in the neurotransmitters, especially norepinephrine, will help alleviate pain in fibromyalgia, arthritis and other pain disorders. SAMe is depleted in liver disease and is a precursor of the critical antioxidant tripeptide glutathione which is a primary protector in cells from free radical damage, and a key molecule in the detoxification process in the liver.

As with the better-known herb St. John’s wort, at least some mainstream psychiatrists are open-minded about SAMe’s possible value. “The nice thing about SAMe is that there is some evidence of efficacy, unlike a lot of other supplements that you can get, which either have not been tested or the evidence does not support their benefit,” says Kathy Harrington, a psychiatrist at the Mayo Clinic College of Medicine and Science. Harrington has recommended SAMe to some of her patients with depression.

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