What is it?

S-adenosyl methionine (SAMe) is a naturally occurring compound that is involved in a variety of biochemical reactions in the body. It is a methyl donor, which means that it donates methyl groups to other compounds, and it is also involved in the synthesis of neurotransmitters and other important molecules. SAMe is also available as a dietary supplement.

What are the mechanisms by which it works for medicinal purposes?

SAMe works as an antidepressant by increasing levels of serotonin, dopamine, and norepinephrine in the brain. It also has anti-inflammatory properties, which makes it effective in treating conditions such as osteoarthritis.

What are the active ingredients that are important for its medicinal properties?

The active ingredient in SAMe is S-adenosyl methionine.

What forms does it come in?

SAMe is available in tablet and capsule form.

What if I have an imbalance or deficiency?

A deficiency in SAMe can lead to depression, liver disease, and joint pain.

When was it first used for medicinal purposes?

SAMe was first used for medicinal purposes in Italy in the 1970s.

Summary:

In one paragraph, S-adenosyl methionine (SAMe) is a naturally occurring substance in the body that has been used for medicinal purposes since the 1970s. It works as an antidepressant by increasing levels of neurotransmitters in the brain and has anti-inflammatory properties. The active ingredient in SAMe is S-adenosyl methionine and it is available in tablet and capsule form. If there is a deficiency or imbalance in SAMe, it can lead to depression and other mental health conditions. The recommended daily dose is 200-400 mg per day and it is best taken in the morning with food. Possible side effects include nausea, diarrhea, stomach upset, and insomnia.

What does S-adenosyl methionine (SAMe) help with?

SAMe is short for S-adenosyl methionine. Your body makes it from methionine, an amino acid, and from ATP, a cell fuel. It takes part in hundreds of chemical steps, including some tied to mood, joints and the liver.

• Low mood and depression
  Strong evidence — repeated randomised trials in people with mild to moderate depression. In clinical trials, SAMe eased mild to moderate low mood. Its effect was close to that of some antidepressant drugs, and people often reported fewer side effects. In lab work, SAMe takes part in making serotonin, dopamine and norepinephrine, three brain chemicals linked to mood and drive.
  Evidence grade A · Traditional tier T0
• Knee and hip pain from osteoarthritis
  Strong evidence — several randomised trials, some against NSAIDs such as ibuprofen. In multiple trials, people with worn knee or hip joints had less pain and moved more easily. Over time the results matched those of NSAIDs like ibuprofen, with milder side effects. In lab work, SAMe spurs cells to make proteoglycans, the building blocks that keep cartilage cushioned.
  Evidence grade A · Traditional tier T0
• Depression that has not lifted with antidepressant drugs
  Good evidence — a randomised placebo-controlled add-on trial from Harvard-affiliated centres. Researchers at Harvard-affiliated centres tested SAMe added to the drug people were already taking. More people responded on the added SAMe than on an added dummy pill. This use is an add-on, not a swap for the drug.
  Evidence grade B · Traditional tier T0
• Widespread pain and stiffness from fibromyalgia
  Early evidence — small human studies with mixed strength. In these studies, people taking SAMe reported less pain, less tiredness and less morning stiffness. Mood also improved, which matters since low mood is common with fibromyalgia. Changes built up slowly, over about four to six weeks.
  Evidence grade C · Traditional tier T0
• Liver strain, fatty liver and bile flow problems
  Early evidence — human studies in alcohol-related liver disease, fatty liver and cholestasis, with mixed results. SAMe has been studied in alcohol-related liver disease, non-alcoholic fatty liver and cholestasis. In those studies, liver enzyme levels fell and liver function tests improved. In lab work, SAMe helps the body top up glutathione, which often runs low in liver disease.
  Evidence grade C · Traditional tier T0
• Intense itching from cholestasis of pregnancy
  Early evidence — European clinical use and human studies, all under medical care. Cholestasis of pregnancy raises bile acids and causes strong itching. In European practice, SAMe has been used to help bile flow and lower bile acid build-up, and women reported less itching. Any use in pregnancy belongs with your doctor, not on your own.
  Evidence grade C · Traditional tier T0
• Anxiety, especially when it comes with low mood
  Evidence doesn't support this — no trial in anxiety alone; reports come from people taking SAMe for mood. People using SAMe for low mood sometimes report feeling calmer. There is no good trial on file testing SAMe for an anxiety problem by itself. The link rests on its role in serotonin and dopamine, shown in lab work.
  Evidence grade D · Traditional tier T0
• Brain fog and mental tiredness
  Not yet tested in people — lab work on methylation only, with no human trial on file. SAMe drives methylation, a chemical step the body uses to make brain chemicals and keep nerve cell membranes in good shape. That role is lab science, not proof of clearer thinking. No human trial on file has tested SAMe for brain fog.
  Evidence grade insufficient · Traditional tier T0

What S-adenosyl methionine (SAMe) has not been shown to do

• It has not been shown to help an anxiety disorder on its own; no trial on file tested that.
• It has not been shown to clear brain fog or sharpen thinking in people; that idea rests on lab work about methylation.
• It has not been shown to work in severe depression; the trials covered mild to moderate low mood.
• It has not been shown to replace an antidepressant drug in people who are not getting enough relief; it was tested as an add-on.
• It has not been shown to cure or reverse liver disease; studies tracked enzyme levels and liver function, not cures.
• It has not been shown to bring fast relief in joint pain or fibromyalgia; in trials the change built over weeks.
• It has not been shown to be safe or useful for itching in pregnancy without a doctor's care.

How to read this:

Each use above carries its own grade. A means several randomised human trials agree. B means at least one good randomised human trial. C means small, mixed or early human studies. D means the human evidence is weak or clashes. Insufficient means no human study at all, only lab or animal work. A high grade for one use does not carry over to another. This page lists options and what studies found. It is not medical advice, and it does not promise a result for you. Talk with your doctor before you start, above all if you are pregnant or already take an antidepressant.

What can it help prevent?

SAMe may help prevent a variety of conditions and symptoms, including:

• Depression
• Liver disease
• Cardiovascular disease
• Alzheimer's disease
• Parkinson's disease
• ADHD
• Anxiety
• Chronic fatigue syndrome
• Migraines
• Fibromyalgia
• Osteoarthritis

Which foods are rich in it?

• Meat
• Fish
• Dairy products
• Eggs

What are possible side effects?

SAMe is generally considered safe when taken as directed, but some people may experience side effects such as:

• Diarrhea
• Nausea
• Diarrhea
• Stomach upset
• Insomnia

What’s the recommended daily dose?

The recommended daily dose of SAMe is 200-400 mg per day.

How many days does it take to work?

It takes approximately 4-6 weeks for SAMe to work as an antidepressant.

What time of day is best to take it?

It is best to take SAMe in the morning with food.

Is it best to take it with or without food?

It is best to take SAMe with food.

Arthritis

200–1,200 mg dailyin divided doses