What to Know About SAMe Supplements (2024)

S-adenosyl methionine (SAMe) is a naturally occurring amino acid found in food. It plays a role in several bodily functions and may offer benefits in treating or preventing liver disease, osteoarthritis, or even depression. More research to confirm SAMe health benefits is needed.

SAMe is thought to interact with many substances in your body, like proteins and lipids (fats). The human-made version of SAMe is thought to work similarly to the natural chemical in your body. More research to confirm SAMe health benefits is needed.

In the United States, the Food and Drug Administration (FDA) does not regulate supplements the way it regulates prescription drugs. That means some supplement products may not contain what the label says. When choosing a supplement, look for third-party tested products and consult a healthcare provider, registered dietitian nutritionist (RD or RDN), or pharmacist.

Uses of SAMe

As with many natural products, people use supplements like SAMe for various reasons. Several studies have assessed SAMe for the following potential uses. However, no supplement is intended to treat, cure, or prevent disease.

Osteoarthritis

Research results are mixed on SAMe for knee or hip osteoarthritis (OA).

Some studies show SAMe may relieve pain and improve joint function with fewer side effects than nonsteroidal anti-inflammatory drugs (NSAIDs) like Advil (ibuprofen). Dosages used include 200 milligrams (mg) three times a day or 400 mg three to six times per day.

Other studies suggest SAMe might not be better than a placebo (a substance with no medication in it). However, some studies may not have used enough SAMe for a long enough period of time for it to be effective.

Depression

SAMe may have some potential use for depression. However, results from a systematic review published in 2016 were inconclusive. Larger, well-designed clinical trials are needed.

Liver Conditions

According to the National Center for Complementary and Integrative Health (NCCIH), low SAMe levels might be linked to liver problems. But research on the potential benefits of SAMe in people with the following liver conditions is mixed:

Alcoholic liver cirrhosis: People with cirrhosis have scarring of the liver. Alcohol use is a potential cause of cirrhosis.
Cholestasis: Cholestasis is a problem with bile (digestive fluid) flow. During pregnancy, the liver may have trouble releasing bile. And the bile buildup may lead to liver function problems.
Hepatitis C: Hepatitis C is a viral infection of the liver. This infection may result in liver inflammation (swelling) and damage in some people.
Metabolic dysfunction-associated steatohepatitis (MASH): In MASH, there is a buildup of fat in the liver. People with this condition may also experience liver inflammation and liver damage. MASH was previously known as nonalcoholic steatohepatitis or NASH.

Using SAMe for intrahepatic cholestasis of pregnancy (ICP), a liver disorder that can cause intense itching without a rash, has mixed reviews. Because taking supplements during pregnancy is not without risks, check with your healthcare provider about SAMe use during pregnancy and learn of the best ways to treat ICP.

What Are the Side Effects of SAMe?

As with many medications and natural products, side effects are possible with SAMe.

Common Side Effects

Side effects with SAMe are rare. But common side effects usually are related to the digestive system. For example, you may experience nausea and stomach upset. Skin rash is another possible side effect.

Severe Side Effects

The NCCIH referred to a study about SAMe in people with alcohol-related liver disease. In this clinical trial, study participants took SAMe for two years with no reports of severe side effects.

Serious side effects may include:

Serious allergic reaction: A severe allergic reaction is a possible side effect of any medication. Symptoms may include breathing difficulties, itchiness, and rash.
Infection risk: SAMe might increase the risk of infection in people with a weakened immune system (the body's defense system). For example, there's a concern that SAMe may support the growth of Pneumocystis jirovecii in people with human immunodeficiency virus (HIV). Pneumocystis jirovecii is a fungus that causes a life-threatening lung infection called Pneumocystis pneumonia.
Mood changes: SAMe may affect your mood. If you have bipolar disorder, a disorder with periods of depression and periods of mania, using SAMe for your depressive symptoms might lead to manic symptoms.
Serotonin syndrome: Similar to many mood medications, SAMe may increase your risk of a rare but life-threatening condition called serotonin syndrome. In serotonin syndrome, high levels of a naturally occurring brain chemical called serotonin develop. Your risk for this condition is further increased if you take SAMe with other medications—like Anafranil (clomipramine)—that also raise serotonin levels. Symptoms may include seizures, sweating, and tremors.

Worsening movement problems: SAMe could interact with medications for the neurological movement disorder Parkinson's disease (PD), worsening movement problems.

If you're having a severe allergic reaction or if any of your symptoms feel life-threatening, call 911 and get medical help right away.

Precautions

SAMe may pose risks in the following situations:

Severe allergic reaction: Avoid SAMe if you have a severe allergic reaction to it or any of its components (parts or ingredients).
Pregnancy: While people might use SAMe for ICP, there's little information about SAMe's effects and safety while pregnant. If you're considering taking SAMe, talk with your healthcare provider about the benefits and risks of SAMe during pregnancy.
Breastfeeding: People might take SAMe shortly after delivering for postpartum depression (PPD). When taken by mouth, SAMe is not well-absorbed into your bloodstream and, therefore, there are no known negative effects on nursing infants, especially if the baby is over 2 months old. But information is still limited on SAMe's effects and safety on nursing babies. If you wish to try SAMe, discuss with your provider the benefits and risks of SAMe while breastfeeding.
Children: Most product labels are directed toward use in adults, not children. Discuss the benefits and risks of SAMe with your child's healthcare provider (pediatrician).

Older adults over 65 years old: Older adults have participated in studies of SAMe for depression, but details regarding safety in this group are lacking. More research with high-quality, larger trials is necessary to learn more about SAMe's effects and safety. However, since older adults may be more sensitive to medication side effects than younger people, they should take SAMe with caution.
People with weakened immune systems: SAMe may increase your risk of infection if you have a weakened immune system. For example, in people with HIV, SAMe might promote the growth of a fungal lung infection from Pneumocystis jirovecii. For this reason, your healthcare provider might recommend against SAMe—especially if you have a very low CD4 white blood cell (WBC) count.
People with bipolar disorder: SAMe might affect your mood. If you have bipolar disorder, using SAMe for depression might lead to a mania episode. For this reason, your healthcare provider might want to monitor you while you're taking SAMe closely.

People with Parkinson's disease: SAMe might work against your PD medications, worsening movement problems. For this reason, your healthcare provider might be cautious about your using SAMe with PD.

Dosage: How Much SAMe Should I Take?

While there are some human studies on SAMe, larger, high-quality, and long-term clinical trials are still necessary. For this reason, there are no guidelines on the appropriate dosage to take SAMe for any condition.

If you take SAMe, follow your healthcare provider's suggestions and product label instructions.

Supplement Facts

Active ingredients (s): S-adenosyl methionine
Alternative name(s): S-adenosyl methionine, S-adenosylmethionine, SAMe, SAM-e, SAM, Adomet, and ademetionine.
Legal status: Over-the-counter dietary supplement in the United States
Suggested dose: May vary based on the dosage form and medical condition
Safety considerations: Limited safety information in pregnancy and breastfeeding; products are intended for adults, not children; may interact with some prescription medications and other supplements

Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs.

What Happens If I Take Too Much SAMe?

There is little information about SAMe toxicity and overdoses in humans. Overdoses with SAMe, however, might be similar to its potential common or severe side effects, which might be exaggerated or excessive.

According to the NCCIH, one study reviewed didn't report any severe side effects with SAMe in a clinical trial over a period of two years in people with alcohol-related liver disease. While side effects with SAMe may be rare, long-term, high-quality studies are still necessary to draw conclusions.

Interactions

Use caution when taking SAMe with the following:

Antidepressants: SAMe may affect your mood. So, similar to many antidepressants, it may increase your serotonin levels. Therefore, SAMe may have additive effects when combined with other antidepressants—like Anafranil (clomipramine). If serotonin levels are too high, there's a risk of a rare but life-threatening condition called serotonin syndrome. Symptoms may include seizures, sweating, and tremors.
Parkinson's disease medications: SAMe may make levodopa less effective. Levodopa often is used in combination with carbidopa. The preferred treatment for PD generally is levodopa-carbidopa medications. By making this treatment less effective, you may experience worsening PD symptoms.

It is essential to carefully read a supplement's ingredients list and nutrition facts panel to know which ingredients and how much of each ingredient is included. Please review this supplement label with your healthcare provider to discuss potential interactions with foods, other supplements, and medications.

How to Store SAMe

Since storage instructions may vary for different natural products, carefully read the directions and packaging label on the container. Keep your medications, including supplements, tightly closed and out of the sight and reach of children and pets, ideally locked in a cabinet or closet. Try to store your medicines in a cool and dry place.

Discard after one year or as indicated on the packaging. Avoid putting unused and expired drugs down the drain or in the toilet. Visit the FDA website to know where and how to discard all unused and expired medications. You can also find disposal boxes in your area.

Ask your pharmacist or healthcare provider if you have any questions about how to dispose of your medications or supplements.

Similar Supplements

Some of SAMe's potential uses may include depression and liver conditions. And a potentially similar supplement is omega-3.

Similar to SAMe, there are human studies on omega-3 for these two medical conditions. But according to the NCCIH, study results on omega-3 for depression are mixed. As with SAMe, further research is warranted with omega-3. Regarding liver conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease or NAFLD), the NCCIH states that results of omega-3 use were either inconclusive or negative.

Omega-3 supplements tend to have mild side effects. Common side effects are also likely related to the digestive system. For example, you might experience nausea, diarrhea, or heartburn. Some people may experience headaches, taste changes, and foul-smelling breath or sweat. And omega-3 might interact with blood thinners, such as Jantoven (warfarin), for drug interactions.

Don't take omega-3 with SAMe until you first talk with your healthcare provider. Doing so can help prevent possible interactions and side effects. Your provider can also ensure you're giving these supplements a good trial at appropriate doses.

Frequently Asked Questions

What is the most common dosage form of SAMe?

SAMe is available in many dosage forms—with tablets likely being the most common.
Is SAMe available from manufacturers in the United States?

Yes. Some SAMe products are manufacturered in the United States.
How do I take SAMe safely?

To safely take natural medications—like SAMe—inform your healthcare providers and pharmacists about any medication changes. This includes over-the-counter (OTC), herbal, natural medications, and supplements.
They can help prevent possible interactions and side effects. They can also ensure you’re giving SAMe a fair trial at appropriate doses.

Sources of SAMe & What to Look For

There are several different sources of SAMe.

Food Sources of SAMe

SAMe is a naturally occurring chemical that's made from methionine, which is an amino acid that's found in food.

Some foods containing methionine are:

Beans
Beef
Cauliflower
Chicken
Cod
Corn
Eggs
Milk
Oats
Pork
Rice
Wheat

SAMe Supplements

SAMe is available in a variety of forms, including capsules and tablets. If you have difficulty swallowing pills, SAMe might also be available in other dosage forms, such as powder. There may also be vegan and vegetarian options.

The product you choose will depend on your preference and what you hope to get in terms of benefits. Each product may work a bit differently depending on the form. Follow your healthcare provider's recommendations or label directions.

Summary