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What Is SAMe & Why Do You Need It?

What Is SAMe & Why Do You Need It?

Have you seen social media posts about a supplement called SAMe? Or perhaps your healthcare provider has recommended that you support a healthy mood or joint health with SAMe supplementation?

SAMe is not your typical vitamin or mineral supplement. This article explores what SAMe does in the body, why your body needs it, and how to support balanced levels. It also explains the benefits and side effects of SAMe. Not everyone needs a SAMe supplement, but if you do, it can make a big difference in how you feel.

What SAMe Does

SAMe is found naturally in the human body. It is an important methyl donor that is highly concentrated in your brain and liver. It participates in methylation reactions where it donates a methyl group to methyltransferase (MT) enzymes.

MT enzymes include:

  • COMT (Catechol-O-Methyltransferase), which is responsible for breaking down estrogen
  • HNMT (Histamine N-methyltransferase), which is responsible for eliminating histamine from your body

Every time SAMe donates a methyl group to your enzymes, their molecular structure and function change. The enzymes can now do important jobs that they couldn’t before, such as:

  • Eliminate histamine to support environmental sensitivities
  • Metabolize estrogen and support hormone balance
  • Break down stress hormones and support feelings of calm
  • Balance neurotransmitters, and make you feel more stable
  • Make healthy bile and optimize your digestion
  • Support healthy sleep and help you feel rejuvenated
  • Produce energy and let you get on with your day

How Your Body Makes SAMe

SAMe stands for S-Adenosyl-l-Methionine. As the name suggests, you make SAMe when methionine is combined with adenosine. You can get both methionine and adenosine from foods.

Foods Needed to Make SAMe

Methionine is an amino acid that contains a methyl group that is donated and participates in all of your methyl transfer reactions. However, methionine cannot donate its methyl group to biochemical reactions on its own. It needs SAMe to do this important job because SAMe can control and regulate methylation reactions better. This allows for just the right amount of methyl donors to be available in your body at any one time. The adenosine-rich foods may be more familiar to your grandparents or great-grandparents. Fewer people consume organ meats these days. But you can also make adenosine through your folate pathway. The ATIC enzyme in the folate pathway is a bifunctional purine biosynthesis protein. It converts 10-Formyl THF produced by MTHFD1L into purines such as adenosine. (1)

The other component of SAMe, adenosine, forms part of adenosine triphosphate (ATP). ATP is adenosine with three phosphate molecules attached to it. The adenosine component of ATP is removed by the MAT1A enzyme in the methylation cycle. It is then added to the sulfur atom of methionine to become S-Adenosyl-l-Methionine or SAMe for short. And that is how your body makes SAMe.

SAMe Recycling

SAMe can also be produced via a recycling process. Once SAMe donates its methyl group, it is converted into a compound called SAH (S-Adenosyl Homocysteine) and eventually homocysteine. Homocysteine is really just methionine (needed to make SAMe) minus a methyl group.

What is SAMe & Why Do You Need It?

In order for homocysteine to become methionine again, it has to pick up a new methyl group from MTR. MTR receives this methyl group from active folate or 5-MTHF (5-methyl tetrahydrofolate) produced by your MTHFR enzyme. The methyl group is then donated to homocysteine via methylcobalamin (active vitamin B12) to become methionine. Methionine then continues towards SAMe production as described above. This is how your body recycles potentially harmful homocysteine into useful SAMe.

Where SAMe Goes Depends on Your Body’s Needs

What is SAMe & Why Do You Need It ?
Up to 80% of your SAMe is used by just two of your enzymes: PEMT (Phosphatidylethanolamine N-methyltransferase) and GAMT (Guanidinoacetate methyltransferase).
What is SAMe & Why Do You Need It?

PEMT is needed to make phosphatidylcholine (PC) for healthy cell membranes and bile flow. A deficiency in phosphatidylcholine may increase the risk of cholestasis, a liver disease where liver function is compromised and the flow of bile from the liver is reduced. In the case of a slow PEMT gene due to inadequate SAMe production, the bile becomes like sludge instead of fluid-like.

The other high SAMe consumer, GAMT, is needed to make creatine for muscle recovery after intense exercise and energy production. The rest of your SAMe is distributed to the rest of your methyltransferase (MT) enzymes to help eliminate histamine, estrogen, and stress hormones. SAMe also supports healthy sleep.

If you are a female of reproductive age, more of your SAMe will go towards breaking down excess estrogen if levels are higher. Likewise, if you are exposed to pollen or irritants, more of your SAMe will be used to clear histamine or go towards the normal breakdown of stress hormones when you are experiencing stressful situations.

When there is increased demand for SAMe to help with all of these functions, often at the same time, you may not have enough SAMe available. This is often the reason why you experience symptoms associated with a SAMe deficiency, such as:

  • Increased irritability
  • Feeling ‘wired but tired’
  • Trouble falling asleep
  • Worsening of skin conditions such as rashes
  • Worsening of seasonal sensitivities
  • Digestive problems
  • Symptoms of estrogen dominance
  • Menstrual difficulties
  • Poor recovery from exercise or feeling worse with exercise

SAMe Supplements

Stability can be a big issue when it comes to SAMe supplements, so quality is key.

Taken as a dietary supplement, SAMe can be quite unstable and degrades easily if exposed to environmental elements such as moisture. (2) It is important that you choose SAMe supplements that are in capsules protected from moisture and kept in air-tight containers.

SAMe is absorbed from the small intestine which makes enteric coated SAMe supplements a better choice to spare as much SAMe as possible from being destroyed by your stomach acid. (3) This is also why it’s better to take SAMe away from food.

When and How Much SAMe Should I Take?

What is SAMe & Why Do You Need It?

It is best to take oral SAMe away from food in order to increase its absorption. Taking it 45 minutes before or 60 minutes after food provides a big enough gap for optimal absorption, but the bigger you can make that gap the better. The amount of SAMe you supplement with depends on your unique circumstances. Your healthcare provider will recommend a serving size based on your needs and/or lab test results.

Typical doses vary from 125 mg to 1200 mg per day, with higher amounts taken in divided doses.

You should not take higher doses without guidance from a healthcare professional. The effects of SAMe are often felt within hours of taking it, with a peak between 3-5 hours. In some cases, effects may only be evident after 1-2 weeks. (4)

Are There Any Side Effects of SAMe?

Since SAMe is involved in so many biochemical reactions, it is possible that side effects may occur. Common side effects often involve mood changes such as:

  • Irritability due to increased conversion of serotonin to melatonin when serotonin levels are already sub-optimal
  • Low mood symptoms due to increased metabolism of dopamine
  • Low estrogen in those who already had sub-optimal estrogen levels

Side effects are more common when the substrates that SAMe converts or metabolizes are sub-optimal to begin with. You will experience fewer side effects if you start with smaller doses when you are not sure whether it is suitable for you. Be aware that if you take high doses of SAMe for an extended period of time, it may cause your CBS (Cystathionine-B-Synthase) enzyme to speed up in an attempt to remove excess SAMe. If your CBS enzyme function is slow, SAMe may increasingly convert to SAH and slow down the function of the very methyltransferase enzymes that you are trying to stimulate through taking SAMe.

Is There Anyone Who Should NOT Take SAMe?

Oral SAMe as a dietary supplement is not suitable for everyone. This is especially true if you are taking any kind of prescription antidepressant such as monoamine oxidase inhibitors (MAOIs). Levodopa is another prescription drug used in Parkinson’s disease that has been shown through clinical studies to interact with SAMe. (5) SAMe can potentially decrease the effects of Levodopa by metabolizing dopamine too quickly. For similar reasons, SAMe should be used with caution in conditions such as bipolar disorder where dopamine levels tend to fluctuate. (6) Even though there are a lot of warnings around SAMe and the use of antidepressants, there have also been clinical studies with some positive indications. (7) It is essential to work with your prescribing physician if you are on any antidepressant medications in order to avoid potential adverse effects with SAMe supplementation.

The Bottom Line

SAMe is a natural and essential molecule in your body needed for many biochemical reactions. Without it, you’d be unable to cope with stressful situations, your digestion would not work well, and you’d constantly have allergy-type symptoms. You would also be at increased risk for certain chronic health conditions the body uses SAMe to regulate gene expression.

You may need to take SAMe as a dietary supplement to support your health, but ultimately you want your body to make and use its own SAMe.

How to Support Your SAMe

  • You need to be able to produce SAMe in adequate amounts for all of its important functions. This involves nutritional intake of protein to provide both methionine and vitamin B12 for SAMe production. It also requires folate from leafy green vegetables for adenosine production, and to donate methyl groups to homocysteine for methionine and eventually SAMe production. A healthy and balanced diet is important.
  • You also need all the cofactors to produce SAMe. This involves bioavailable vitamin B12 from animal protein sources and zinc for healthy MTR function.
  • You need good digestion and stomach acid release to support folate, vitamin B12, and methionine absorption from food. If you feel you are not digesting your food properly, consider support with a comprehensive digestive enzyme.
  • Most importantly, remember that SAMe has a lot of jobs to do. If you bombard your body with too much stuff, i.e. chronic stress, allergen exposure, and too much estrogen, it may get overloaded. Deal with things that can disrupt SAMe and support your overall health in the process.

If you’re seeking supplemental support for SAMe, speak with your healthcare team about trying SAMe supplements. SAMe by Seeking Health provides 125 mg of SAMe in each protective, acid-resistant vegetarian capsule. To optimize stability and prevent degradation upon exposure to environmental factors, the capsules are protected from moisture and air via a desiccated bottle.

Get supplemental SAMe here
What is SAMe & Why Do You Need It?


  1. V. Baresova et al., “Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency,” Hum. Mol. Genet., vol. 21, no. 7, pp. 1534–1543, Apr. 2012, doi:10.1093/hmg/ddr591.
  2. V. Lauruengtana et al., “Formation of spray-dried powder of S-adenosyl-L-methionine,” Biotechnol. J., vol. 5, no. 5, pp. 470–476, May 2010, doi: 10.1002/biot.200900290.
  3. G. Bombardieri, G. Pappalardo, L. Bernardi, D. Barra, A. Di Palma, and G. Castrini, “Intestinal absorption of S-adenosyl-L-methionine in humans,” Int. J. Clin. Pharmacol. Ther. Toxicol., vol. 21, no. 4, pp. 186–188, Apr. 1983, [Online]. Available:
  4. G. M. Kapalka, “ADHD,” Nutritional and Herbal Therapies for Children and Adolescents. pp. 101–140, 2010. doi: 10.1016/b978-0-12-374927-7.00005-4.
  5. T. Müller, B. Fowler, and W. Kuhn, “Levodopa intake increases plasma levels of S-adenosylmethionine in treated patients with Parkinson disease,” Clin. Neuropharmacol., vol. 28, no. 6, pp. 274–276, Nov. 2005, doi: 10.1097/01.wnf.0000190800.87380.c7.
  6. T. R. Berigan, “A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe),” Prim. Care Companion J. Clin.Psychiatry, vol. 4, no. 4, p. 159, Aug. 2002, doi: 10.4088/pcc.v04n0408b.
  7. A. Sharma et al., “S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research,” J. Clin. Psychiatry, vol. 78, no. 6, pp. e656–e667, Jun. 2017, doi: 10.4088/JCP.16r11113.

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