Evidence: High Possible Benefits: Very High Safety: High
TABLE OF CONTENTS
What is SAM-e?
S-Adenosyl methionine, also known as SAMe or SAM-e, is a chemical vital in the process called methylation, where it acts as a methyl donor. SAMe is commonly used as a dietary supplement for its wide variety of benefits. This article is about the main benefits of SAM-e, its potential side effects, the best time to take it, and more.
Possible benefits
All of the potential benefits mentioned below are dose-dependent. As with most other supplements, there is a sweet-spot dose that allows you to get most of the benefits without causing meaningful side effects or tolerance buildup in the body. We will discuss the best dosing protocol later in this article.
Major benefits
Reduced symptoms of osteoarthritis – This benefit is significant and highly reliable. SAMe can also improve joint health in older people without osteoarthritis to some degree.
Reduced symptoms of depression – SAMe can be as potent as tricyclic antidepressants (TCAs) for reducing depression but with a much better safety profile. The supplement can also enhance the effects of SSRIs.
Improved liver health – SAM-e is synthesized in the liver. When the liver cannot function properly, the body cannot produce enough SAMe. Taking this compound exogenously can help the body function better in instances of liver damage. The supplement can also improve liver health and help heal cholestasis, alcoholic liver disease, and possibly non-alcoholic fatty liver disease (NAFLD).
Reduced pain – The supplement can greatly reduce chronic pain. It is similar in potency to many pharmaceutical painkillers but generally much safer. The main downside is that SAMe requires more time to reduce pain and has to be taken regularly for at least a month to have an effect.
Minor benefits
Improved memory – An improvement was only found in people who take SSRIs so far. The benefit may apply to other groups of people but more research is needed.
Reduced symptoms of folate deficiency – SAMe can replace some functions of folate (vitamin B9) related to methylation, which is why it can reduce the symptoms of folate deficiency.
Possible side effects
The side effects below are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.
Sedation – SAM-e can cause mild sedation.
Reduced numerical memory – One study found a worsened numerical memory in older people taking the supplement. This benefit is likely to SAM-e’s sedative effects.
Mania – While uncommon, some people report mania after they start taking SAM-e. The reason for this effect is still unknown.
Allergic reaction – An allergy to this supplement is rare but possible.
Nausea – This side effect is most common when people take the supplement on an empty stomach.
Diarrhea – You can usually prevent diarrhea or stomach discomfort by taking this supplement with a meal.
Toxicity – While acute toxicity is extremely rare, taking high amounts of this supplement could lead to chronic toxicity and cause health problems over time. Regularly taking high doses can also cause the body to develop a tolerance to the supplement. To prevent chronic toxicity or the buildup of tolerance, staying below 1200 mg in a day is best unless you have a great reason to take more.
Contamination – Contaminated supplements are uncommon in the USA and other well-regulated countries. However, if you wish to buy products from China, India, or other countries without strict regulations, beware that the supplements may be contaminated. Either way, you need to choose the brand you order from wisely. Always read through some reviews for the specific product before you buy it. The FDA (Food and Drug Administration) has the power to regulate dietary supplements but can only do so after they have been on the market for a while. That’s because supplement companies are not obligated to announce to the FDA when releasing a new product. The FDA has to discover the product and test it for potential impurities, which can take a lot of time. During that time, the supplement can be sold on the market even if it’s impure. Also, supplement companies can change their manufacturers without announcing it to the FDA.
Who should not take SAM-e?
You should probably avoid taking SAM-e if you:
have an MTHFR (methylenetetrahydrofolate reductase) gene mutation – In this case, SAMe can cause an accumulation of homocysteine, a potentially harmful metabolite. If you have an MTHFR gene mutation, methylfolate or TMG are generally safer alternatives.
are allergic to this supplement
experience a severe adverse reaction after taking the supplement
are pregnant or breastfeeding (while it can be safe to take this supplement during pregnancy or breastfeeding, it can put some unnecessary risk to the child)
have a high budget for supplements and are willing to experiment with a variety of them (assuming you don’t fall into any of the categories that should avoid this supplement, SAM-e appears relatively safe and is unlikely to do more harm than good for most people)
How much SAM-e should you take?
The sweet spot dose typically ranges between 600-1200 mg daily for most people. This amount should provide most of the benefits without meaningful side effects.
The higher end of this range usually provides slightly more benefits in the short term. If you plan to take this supplement for a longer time (multiple months or years), the lower end is probably a better way to go since it is safer, and you would develop tolerance faster if you were to take higher doses.
The upper safety limit for this supplement is not well-established. To stay on the safe side, don’t take more than the recommended dose unless you have a great reason to do so. Higher amounts may cause problems if you take the supplement for a prolonged period.
Like most other supplements, it is best to cycle SAM-e and take about two days off weekly to reset your tolerance. That will allow you to keep getting the benefits in the long term.
Best time to take SAM-e
SAM-e is fat-soluble, so you should always take it with food or a dietary source of fat to absorb it well.
Whether you take the supplement in the morning or the evening does not make much difference. Both options are fine so feel free to experiment.
Interactions
Folate SAMe can replace some functions of folate related to methylation, which is why it can reduce the symptoms of folate deficiency. Methylfolate is a great replacement for SAMe in people with an MTHFR gene mutation.
Riboflavin SAMe can increase homocysteine levels with MTHFR gene mutations. Riboflavin can significantly reduce homocysteine levels in these individuals and greatly lower the side effects and improve the safety profile of SAMe. As little as 1.6 mg of supplemental vitamin B2 can lower homocysteine by around 40%, which is a significant improvement.
L-DOPA At least one study shows that L-DOPA may deplete S-adenosyl Methionine levels in children. This likely applies to adults as well.
SSRIs SAM-e can increase the effects of SSRIs and acts synergistically with these anti-depressants in some ways. For example, people on SSRIs often experience improvements in memory when they start taking SAMe. Beware that the combination can also lead to more side effects caused by SSRIs, especially at high doses.
Where to buy SAM-e?
In most countries, Amazon is the best option for ordering SAM-e supplements. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the Internet.
Some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.
FAQ
Like most other supplements, it is best to cycle SAM-e and take a break from it for about two days per week to reset your tolerance back to baseline. That will keep your body sensitive to the supplement and allow you to keep getting the benefits in the long term.
All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, you may need a highly accurate scale to dose them correctly (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes time which can add up over months or years. The disadvantage of capsules is that they are often made of bovine gelatine, which rarely comes from ethical sources.
The supplement by itself should not worsen your sleep quality in any way. However, it’s best to take it with food, and you generally don’t want to eat any food right before bed as it could worsen your digestion and sleep quality.
This supplement should not become harmful once it exceeds the expiration date. However, it can lose potency over time. Keep this supplement in a cold, dark, and dry place so it remains as potent for many months or even years.
While acute toxicity is rare, taking very high amounts of this supplement could lead to various problems over time. High doses can also make you develop tolerance much faster than lower doses.
While you could safely take higher doses, there is usually no point in taking more than 1200 mg daily. This amount should give you most of the benefits without meaningful side effects.
The half-life of SAM-e in the body is about 100 minutes. This supplement gets metabolized within 7 hours after you consume it. However, most of the effects of this supplement are cumulative, so they mainly happen in the long term rather than acutely. Therefore, the half-life of this supplement isn’t very relevant in practice.
In the long term, you must take the supplement for about 2-4 weeks to begin noticing most of the benefits.
Most SAMe supplements on the market are vegan-friendly, but always check the label to assure yourself. If you buy the supplement in a capsulated form, beware that the capsules often contain animal-based gelatin. Instead, find a brand that puts its products into cellulose capsules.
No, it does not. The supplement should not interfere with fasting in any significant way. However, you still want to take the supplement with food as it will absorb better.
References
Most of the information in this guide is based on scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything you read in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.
