SAMe Uses, Side Effects, & More

S-adenosyl methionine (SAMe) is a naturally occurring amino acid found in food.

SAMe plays a role in several bodily functions. It does this by interacting with many substances in your body, like proteins and lipids (fats). So, the human-made version of SAMe is thought to work similarly to the natural chemical in your body.

This article discusses what you should know about SAMe—its potential uses, side effects, interactions, and more.

Uses of SAMe

Like many natural products, people may use SAMe for various reasons. But there are several studies assessing SAMe for the following potential uses.

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) 3 times per day or 400 milligrams 3 to 6 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 were inconclusive. Larger, well-designed clinical trials are needed.

Liver Conditions

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

• Alcoholic liver cirrhosis: In general, people with cirrhosis have scarring of the liver. Alcohol use is a potential cause of cirrhosis.
• Cholestasis: In general, cholestasis is a problem with bile (digestive fluid) flow. During pregnancy, the liver may have trouble releasing bile. And the bile build-up 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.
• Nonalcoholic steatohepatitis (NASH): In NASH, there is a build-up of fat in the liver. People with this condition may also experience liver inflammation and damage.

Using SAMe for intrahepatic cholestasis of pregnancy (ICP) has mixed reviews. Taking supplements during pregnancy is not without risks. Check with your healthcare provider about current best practices for ICP and the best treatment for you. 

What Are the Side Effects of SAMe?

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

Common Side Effects

In general, side effects with SAMe are rare. But common side effects are typically related to the digestive system. For example, you may experience nausea and stomach upset. Skin rash is also 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. But possible 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 life-threatening fungal infection in the lungs.
• Mood changes: SAMe may affect your mood. If you have bipolar, using SAMe for depression might lead to mania. In bipolar disorder, you may experience mood swings between mania and periods of depression.
• Serotonin syndrome: Similar to many mood medications, SAMe might increase your risk of a rare but life-threatening condition called serotonin syndrome. In serotonin syndrome, there are high levels of a naturally-occurring brain chemical called serotonin. 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 might interact with Parkinson’s disease (PD) medications, 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 its components (parts or ingredients).
• Pregnancy: While people might use SAMe for intrahepatic cholestasis of pregnancy (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 pregnancy for postpartum depression (PPD). When taken by mouth, SAMe isn’t well-absorbed into your bloodstream. Also, SAMe isn’t expected to be linked to negative effects on nursing infants, especially if the baby is over two months old.
• But there is still limited information about SAMe’s effects and safety on nursing babies. If you want to take SAMe, discuss the benefits and risks of SAMe while breastfeeding with your healthcare provider.
• Children: Most product labels seem intended for 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 did participate in some studies included in a systematic review (review of a collection of studies) of SAMe for depression. But more research with high-quality and larger studies is necessary to know more about SAMe’s effects and safety. Moreover, some older adults may be more sensitive to medication side effects. For this reason, 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: SAMe might affect your mood. If you have bipolar, 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 (PD): SAMe might work against your PD medications, worsening movement problems. For this reason, your healthcare provider might be cautious about 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.

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.

But the NCCIH mentioned that a study didn’t report any severe side effects with SAMe for two years in a clinical trial of people with alcohol-related liver disease. While side effects with SAMe seem rare, long-term and high-quality studies are still necessary.

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 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 (PD) medications: SAMe may make levodopa less effective. Levodopa is typically 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 ingredient 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. But in general, keep your medications tightly closed and out of the 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’s 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. So, like SAMe, further research is warranted. As for liver conditions—like nonalcoholic fatty liver disease (NAFLD), the NCCIH states that results were either inconclusive or negative.

As for safety, omega-3 also tends 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 bad-smelling breath or sweat. And omega-3 might interact with blood thinners, such as Coumadin (warfarin), for drug interactions.

Don’t take omega-3 with SAMe until you first talk with your healthcare provider. They can help prevent possible interactions and side effects. They can also ensure you’re giving these supplements a good 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 that contain some methionine may include:

• 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 difficulties swallowing pills, SAMe might also be available in other dosage forms, such as powder. There may also be vegan and vegetarian options.

The specific product you choose will depend on your preference and what you hope to get in terms of effects. Each product may work a bit differently depending on the form. So, it’s important to follow your healthcare provider’s recommendations or label directions.

Summary

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

SAMe may have potential uses for osteoarthritis, depression, and liver conditions. Side effects are generally rare. But similar to many medications and natural products, side effects and medication interactions are still possible.

More high-quality research with larger, well-designed, and long-term clinical trials is necessary to assess SAMe’s effectiveness and safety. Before taking SAMe, contact your pharmacist or healthcare provider to help you safely achieve your health goals.