Top 5 SAM-e Supplements

SAM-e Benefits, dosages, and supplementsSAM-e (S-adenosylmethionine) is a compound that circulates throughout the body and functions in virtually every cell. Our bodies create SAM-e naturally, but in certain conditions, supplementation may be beneficial, as the amount produced may not be sufficient.

So, What Exactly is SAM-e?

SAM-e is an intermediary by-product that is created during the metabolism of methionine.

Translation: it’s the middle-man between two major amino acids.

Methionine is an essential amino acid, a part of protein. It is broken down by certain enzymes to produce SAM-e (S-adenosyl-methionine).

During this process, SAM-e is equipped with a methyl group (CH3). SAM-e is often referred to as a “universal methyl donor”, meaning that it donates its methyl group wherever it is required. Many processes such as DNA metabolism and neurotransmitter synthesis require SAM-e to donate a methyl group [2]. Methylation is needed for:

  • Detoxification of toxins and chemicals
  • Energy production
  • DNA and RNA expression
  • Neurotransmitter synthesis and function
  • Regulating inflammation
  • Reducing oxidative stress

SAM-e and the Methionine Cycle

After SAM-e donates its methyl group wherever it’s needed, it is converted into another amino acid called homocysteine. This process is known as the “methionine cycle” – remember that methionine was the initial ingredient to create SAM-e?

Homocysteine can either convert back to methionine with the help of vitamin B12 and folate, or be further metabolised into another amino acid called cysteine with the help of vitamin B6.

Homocysteine has a variety of roles in the body, including cell signalling and inflammation regulation. High levels have been linked to problems such as heart disease and Alzheimer’s disease, but it’s complicated – we’ll get to that in the minute!

SAM-e, Glutathione & Other Antioxidants

SAM-e is said to have antioxidant actions, but this isn’t directly true. The “methionine cycle” can result in the production of glutathione – the body’s most potent antioxidant. It’s a long process to get there, but SAM-e is a key ingredient in its creation, and studies have found that supplementing with SAM-e can increase glutathione concentrations in the liver [22].

Through its roles RNA and DNA expression, SAM-e is also able to boost the expression of antioxidant enzymes such as super oxide dismutase [22].

Okay, so what exactly is SAM-e good for?

Given its key role in methylation, there are many conditions that would benefit from SAM-e. Here are the key areas of research on SAM-e:

6 Primary Benefits of SAM-e Supplements

Cardiovascular Health

Homocysteine is a major biomarker for cardiovascular risk. High levels of homocysteine have been shown to have a damaging effect on the arterial walls. One study also found a correlation with increased serum homocysteine and central arterial stiffness in an elderly population – a big risk factor for atherosclerosis [3].

As we mentioned above, SAM-e is converted into homocysteine through the methylation pathway. You might assume that high levels of SAM-e lead could lead to high levels of homocysteine – but you’d be wrong. Rather than leading to an accumulation of homocysteine in the body, SAM-e actually lowers homocysteine levels by up-regulating its complete conversion into cysteine [1].

  • One double-blind, placebo controlled, randomized study showed that supplementing SAM-e did not increase plasma homocysteine levels in healthy subjects. Rather, it helped to increase co-factors in homocysteine metabolism, therefore having the potential to reduce homocysteine levels [4].

SAM-e for Osteoporosis

As an anti-inflammatory and antioxidant compound, SAM-e may relieve the pain and symptoms of inflammation associated with osteoarthritis. It also appears to exert specific protective effects on joint cartilage by altering DNA and RNA expression to prevent further degradation of the joints [16].

  • A 2011 meta-analysis of six randomised controlled trials, and an earlier meta-analysis from 2002, both found that a daily dose of 1,200mg of SAM-e per day was as effective as standard medication treatments including as celecoxib, ibuprofen and naproxen, with much lower participant drop-out rates in the SAM-e groups than the medication groups [16][17].

SAM-e for Mood and Nervous System Support

SAM-e’s methyl donation is crucial step in neurotransmitter synthesis. Neurotransmitters are “brain chemicals”, involved in stimulating and maintaining mood, cognition, memory, perception and more. An imbalance in neurotransmitters is associated with conditions including depression, schizophrenia and Alzheimer’s disease.

  • SAM-e may be a beneficial co-treatment in Major Depressive Disorder (MDD). One study looked at the effects of SAM-e in people who didn’t respond to anti-depressant drugs such as SSRIs. The researchers concluded that taking SAM-e alongside SSRIs was more beneficial effect than taking a placebo or the SSRI on its own [5].
  • Another study demonstrated that supplementing SAM-e for 8 weeks reduced Major Depressive Disorder symptoms in people with HIV/AIDS. Results were rapid with few side effects [6]. Note: There are limitations in this study including small sample size and no placebo control group.
  • SAM-e has been a supplement of interest in the treatment of schizophrenia, with one study showing a reduction in aggressive behaviour after 8 weeks of a 800mg dose per day [7]. NOTE: SAM-e is not a proven therapy for any mental health conditions and must be taken under supervision in schizophrenia. Speak to your doctor and psychiatrist before taking SAM-e.
  • SAM-e may also be a beneficial treatment in Alzheimer’s disease with limited side effects. SAM-e levels are reduced in patients with Alzheimer’s disease and supplementation has been shown to improve cognitive performance and decrease aggressive behaviour [8] [9].

It is important to note that SAM-e should be cautioned in all conditions unless prescribed by a specialist. Particular caution should be used in bipolar disorder and Parkinson’s disease.

SAM-e for Fibromyalgia

The effects of SAM-e in depression may have cross-over effects to fibromyalgia. Symptoms of fibromyalgia pain and fatigue have been shown to improve with the use of SSRIs in patients with co-current depression; although the mechanism of why is still unknown, anything involved in neurotransmitter balancing (such as SAM-e) may also have positive effects on fibromyalgia.

  • Four double-blind trials have looked at the effects of SAM-e in fibromyalgia, and all of them reported positive results. In them, SAM-e was shown to improve pain scores, reduce fatigue, frequency of migraines, and relieve morning stiffness. [18] [19] [20] [21]

SAM-e for Liver Health

SAM-e is predominantly produced in the liver and skeletal muscle. When the liver is compromised, so is SAM-e. But it appears that SAM-e and liver cells have a mutually beneficial relationship: supplementing with SAM-e may be an effective co-therapy for liver diseases.

  • A 2015 systematic review and meta-analysis of SAM-e in liver disease demonstrated that it has the ability to reduce some liver enzymes that are raised in liver disease, therefore being a useful aid in treatment. Keep in mind that the results of this study also showed that SAM-e was not more effective than specific medications for liver disease, but it should still be considered in a treatment regimen to aid in recovery [13].
  • In 2011, a study demonstrated that SAM-e may be a beneficial add-on treatment for viral hepatitis C non-responders [10].
  • A more recent 2015 study demonstrated that plasma levels of SAM-e may be a useful test or biomarker to analyse the severity of Hepatitis B-related liver disease [11], suggesting that higher levels of SAM-e are associated with less disease progression.

But SAM-e has its limitations. Although generally considered as a beneficial treatment in improving liver function, one double-blinded, randomised, placebo-controlled trial showed that 1.2g of SAM-e per day for 24 weeks was no more effective than placebo in treatment of alcoholic liver disease compared to a placebo [12]. Abstinence was shown to improve liver function way more than both placebo and/or SAM-e.

SAM-e in Epigenetics and Gene Alteration

SAM-e may be able to alter gene expression. This is a very interesting concept and dabbles into the world of “epigenetics”, which explores the hypothesis of altering genetic expression rather than altering the gene or DNA sequence itself.

SAM-e can support gene expression by donating a methyl group to each DNA molecule during its synthesis and expression. Without the methyl group, certain genes can’t be expressed, while others may get “switched on”.

Here are some of the ways SAM-e may be beneficial in protecting our genes –

  • One study has shown that supplementation of SAM-e with a drug for lung cancer protected the anticancer activity of the drug. It did this by modulating DNA methylation [14].
  • Another study has shown that SAM-e has the ability to decrease pro-inflammatory cells and increase anti-inflammatory cells through DNA methylation, showing it’s possible that SAM-e has the ability to alter inflammatory gene expression [15]. It may be able to reduce inflammation in a wide range of conditions.

How to Take SAM-e

In Europe, SAM-e is administered in injectable forms from certified practitioners. Oral doses are tricky – SAM-e has poor bioavailability and a lot of it is destroyed during first-pass liver detoxification. Some SAM-e will make it into the blood stream, but the amount is unpredictable between individuals. Because of this variability, it’s uncertain how any individual will react, always start with a low dose.

DOSAGE: A dose of 200 mg per day is a good starting point for most people.

Up to 2,000 mg per day has safely been used for low mood, but doses of 400mg – 600mg are found to be effective for most people.

If taking higher doses, divide these into 400 mg increments to maximise absorption.

Take on an empty stomach before food unless this causes nausea.

Improvement has been reported at around 1 week for low mood, and up to 4 weeks for osteoarthritis, and over 6 weeks for its effects on fibromyalgia to be significant.

Speak to a qualified nutritionist or naturopath before beginning SAM-e treatment to ensure it is safe and appropriate for your condition.


Taking SAM-e supplements may cause or contribute to agitation, restlessness, and feelings of anxiety.

Bipolar manic episodes can be set off by SAM-e. People suffering from ANY mental health conditions should be aware that it is NOT advisable to take SAM-e unless under the approval and supervision of a qualified physician.

Do NOT take SAM-e if pregnant or breastfeeding.

Gastrointestinal side effects include bloating, gas and flatulence – it may exacerbate symptoms of any pre-existing conditions involving the gut, including IBS.

Top 5 SAM-e Supplements

#5 Doctor’s Best SAM-e (200mg, 60 enteric coated capsules)

SAM-e SupplementsDoctor’s Best have packaged a low dose of 200mg of SAM-e in enteric coated capsules to ensure maximum absorption. These come in an easy-to-use blister pack that protects the SAM-e from degradation. This is a soy-free, gluten-free and vegan-friendly choice at a low price. Great if you’re looking to start on a relatively low dose – Doctor’s Best SAM-e gives you the option to begin with just one tablet of 200mg per day.

#4 EZ Melts SAM-e (200mg, 60 dissolvable tablets)

SAM-e CapsulesMint flavoured SAM-e tablets – the future is here! EZ Melts have created fast-melting tablets with sublingual delivered SAM-e. Some reviewers on Amazon suggest that the taste gets a bit boring after a while, but these are a great way to mix up your supplement regime. They are 100% vegan, non-GMO, with all natural flavours, colours and sweeteners – a no-brainer, fun choice if you have problems with swallowing pills or just want to try a new of getting a dose of SAM-e.

#3 Nature’s Trove SAM-e (400mg, 90 enteric coated capsules)

SAM-eNature’s Trove use a SAM-e that contains the highest level of active components available on the market. Each capsule contains 400mg of SAM-e in an enteric coated capsule – that means that the SAM-e is protected against digestion in the stomach and can travel safely to the intestines for absorption. They also publish their certificate of quality on Amazon – easy to see that this product is free from heavy metals, and that the SAM-e is actively potent. The packaging makes it easy to get the capsules out, and just one a day is a perfect starting dose for most people.

This SAM-e supplement is certified as kosher, and contains no common allergens, or any animal byproducts.

#2 NuScience Cell Food SAM-e Liquid Formula (1fl oz)

Liquid SAM-e SupplementNuScience have combined a liquid SAM-e with their patented Cell Food formula – a combination that is designed to give all the benefits of SAM-e with added antioxidant activity and oxygen support. The minerals in this liquid are negatively charged to boost absorption into circulation and through cell membranes.

This is a great formula if you’re looking for an easy way to get concentrated SAM-e into the body, particularly if you have digestive issues. Because of the optimised absorption formula, 75mg of this liquid is said to deliver an equivalent 400mg dose.

Keep in mind that SAM-e is degraded by light and heat, so mix this liquid formula with honey or water just moments before you take it.

#1 NeuroScience AdrenCor with SAM-e (200mg, 30 capsules)

Neuro Science SAM-eThis supplement combines SAM-e with all the nutrient co-factors it needs to boost neurotransmitters and relieve stress – B group vitamins, magnesium, zinc and a proprietary blend of herbs and amino acids. Each capsule contains 200mg of SAM-e and good doses of other nutrients, which is a great starting dose. This synergistic blend is designed support balanced mood, relieve stress, and support energy production.

View AdrenCor on Amazon

Further Reading: 

  • [1] Obeid, R. (2013). The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway. Nutrients5(9), 3481–3495.
  • [2] Moore, L. D., Le, T., & Fan, G. (2013). DNA Methylation and Its Basic Function. Neuropsychopharmacology38(1), 23–38.
  • [3] Zhang, S., Bai, Y.-Y., Luo, L.-M., Xiao, W.-K., Wu, H.-M., & Ye, P. (2014). Association between serum homocysteine and arterial stiffness in elderly: a community-based study. Journal of Geriatric Cardiology : JGC11(1), 32–38.
  • [4] Thompson, M. A., Bauer, B. A., Loehrer, L. L., Cha, S. S., Mandrekar, J. N., Sood, A., & Wahner-Roedler, D. L. (2009). Dietary Supplement S-Adenosyl-l-Methionine (AdoMet) Effects on Plasma Homocysteine Levels in Healthy Human Subjects: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Journal of Alternative and Complementary Medicine15(5), 523–529.
  • [5] Papakostas, GI., Mischoulon, D., Shyu, I, Alpert, J.E. & Fava, M, (2010). S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. American Journal of Psychiatry, 167(8), pp: 942-8. DOI: 10.1176/appi.ajp.2009.09081198.
  • [6] Shippy, R. A., Mendez, D., Jones, K., Cergnul, I., & Karpiak, S. E. (2004). S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS. BMC Psychiatry4, p. 38. MEDLINE Complete, EBSCOhost
  • [7] Strous, R.D., Ritsner, M.S., Adler, S., Ratner, Y., Maayan, R., Kotler, M., Lachman, H. & Weizman, A. (2009). Improvement of aggressive behaviour and quality of life impairment following S-Adenosyl-Methionine (SAM-e) augmentation in schizophrenia. European Neuropsychopharmacology, 19(1), pp: 14-22. DOI:
  • [8] Rudolph, M. L., Rabinoff, M., & Kagan, B. L. (2011). A prospective, open-label, 12 week trial of S-adenosylmethionine in the symptomatic treatment of Alzheimer’s disease. Neuroscience & Medicine, (3), 222.
  • 9] Shea, T. B., & Chan, A. (2008). S-Adenosyl Methionine: A Natural Therapeutic Agent Effective Against Multiple Hallmarks and Risk Factors Associated with Alzheimer’s Disease. Journal Of Alzheimer’s Disease13(1), 67-70
  • [10] Feld, J. J., Modi, A. A., El-Diwany, R., Rotman, Y., Thomas, E., Koh, C., … Liang, T. J. (2011). S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. Gastroenterology140(3), 830–839.e3.
  • [11] Li, T., Yu, G., Guo, T., Qi, H., Bing, Y., Xiao, Y., … Liu, Q. (2015). The Plasma S-adenosylmethionine Level is Associated With the Severity of Hepatitis B-Related Liver Disease. Medicine94(4), e489.
  • [12] Medici, V., Virata, M. C., Peerson, J. M., Stabler, S. P., French, S. W., Gregory, J. 3., & … Halsted, C. H. (2011). S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. Alcoholism, Clinical And Experimental Research, 35(11), 1960-1965. doi:10.1111/j.1530-0277.2011.01547.x
  • [13] Guo, T., Chang, L., Xiao, Y., & Liu, Q. (2015). S-Adenosyl-L-Methionine for the Treatment of Chronic Liver Disease: A Systematic Review and Meta-Analysis. Plos ONE10(3), 1-17. doi:10.1371/journal.pone.0122124
  • [14] Ham, M.S., Lee, J.K., & Kim, K.-C. (2013). S-adenosyl methionine specifically protects the anticancer effect of 5-FU via DNMTs expression in human A549 lung cancer cells. Molecular and Clinical Oncology1(2), 373–378.
  • [15] Pfalzer, A. C., Sang-Woon, C., Tammen, S. A., Park, L. K., Bottiglieri, T., Parnell, L. D., & Lamon-Fava, S. (2014). S-adenosylmethionine mediates inhibition of inflammatory response and changes in DNA methylation in human macrophages. Physiological Genomics46(17), 617-623.
  • [16] De Silva V., et al. (2011) Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology, 50, 911–920.
  • [17] Soeken, K. L., et al. (2002) Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract 51.5, 425–430.
  • [18] Jacobsen, S., et al. (1991) Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol 20:4, 294–302.
  • [19] O’Malley, P. G., et al. (2000) Treatment of fibromyalgia with antidepressants: a meta-analysis. J Gen Intern Med, 15:9 , 659–666.
  • [20] Volkmann, H., et al. (1997) Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-l-methionine in patients with fibromyalgia. Scand J Rheumatol., 26:3, 206–211.
  • [21] Sarac, A. J. & Gur, A. (2006) Complementary and alternative medical therapies in fibromyalgia. Curr Pharm Des, 12:1, 47–57.
About James Lyons

James Lyons (BHSc Nutritional Medicine) is a clinical nutritionist, medical writer, and educator. He specialises in plant-based nutrition and is passionate about improving public access to reliable and accurate health information.

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