The Health Benefits of SAM-e: For Depression, Joint Relief, and More

 

SAM-e is short for S-adenosyl-L-methionine, a molecule that is essential for the function of virtually every cell in the body. Often referred to as the “universal methyl donor”, SAM-e provides methyl groups for over 100 different enzymatic reactions and essential processes such as DNA metabolism and neurotransmitter synthesis. Recent research has shown that SAM-e can be a highly effective way to treat depression and various mood disorders.

For more than eight years, Richard P. Brown, M.D., associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons, has used the natural dietary supplement SAM-e to treat more than an estimated 400 patients suffering from depression, many of whom were treatment-resistant. Brown said that considering SAM-e’s efficacy in treating depression, its mild side-effect profile, and its ability to boost antioxidants and protect DNA through methylation, this nutrient has advantages over prescription antidepressants.

Methyl groups from SAM-e are essential for the synthesis and function of neurotransmitters – “brain chemicals” that are used for stimulating and sustaining mood, focus, memory, cognition and sleep. Major imbalances in neurotransmitters are associated with conditions including depression, schizophrenia and Alzheimer’s disease.

Major Depressive Disorder is frequently treated with SSRI medications, and SAM-e is considered a beneficial co-treatment. A 2010 study found that SSRIs were more effective in patients who also took SAM-e [5].

A smaller study in 2004 looked at the effects of taking SAM-e for major depressive disorder in people with HIV/AIDS. The participants took SAM-e for 8 weeks and the results showed a rapid improvement in symptoms with few side effects [6].

Hereditary disease, schizophrenia may be linked to DNA methylation issues. SAM-e has researched as a co-therapy in the treatment of schizophrenia, and a key study has shown a reduction in aggressive behaviour after 8 weeks of a 800mg dose per day [7].

Studies have shown that SAM-e levels are often low in patients with Alzheimer’s Disease. Supplementation has been seen to improve cognitive performance and decrease aggressive behaviour in clinical trials [8] [9].

 

SAM-e for Joint Pain

Osteoarthritis (OA) attacks the cartilage of large joints, such as knee or hip. It causes joint pain and stiffness, which reduce patients’ quality of life [19].

A review of clinical studies with over 20,000 patients supports the use of SAM-e for osteoarthritis. It has the same effect as commonly-used NSAIDs with fewer side effects [20, 21].

In a Cochrane review of four trials with 656 patients, SAM-e moderately improved pain and joint function, compared with placebo [22]. Additionally, several animal studies have shown that SAM-e can stimulate the production of cartilage, which shows promising results and will help all manner of arthritis patients.

Given that long-term treatment with NSAIDs and other painkillers may cause stomach ulcers and other adverse effects, SAM-e could be a safer yet equally effective alternative [23].

SAM-e for Cardiovascular Health

High levels of homocysteine is a risk factor for cardiovascular disease. Hyperhomocysteinemia  – excessive levels of homocysteine in the blood – has been shown to cause damage to walls of blood vessels.

A study in 2014 also found a connection between elevated serum homocysteine and central arterial stiffness in an elderly population – a big risk factor for atherosclerosis [14]. As covered above, SAM-e is converted into homocysteine through the methionine cycle and methylation pathway – so wouldn’t high levels of SAM-e lead to elevated homocysteine levels? As it turns out, no! Rather than causing a boost to homocysteine levels in the body, SAM-e has been shown to actually lower homocysteine levels by up-regulating its complete conversion into cysteine and the antioxidant glutathione [15].

A 2009 study demonstrated that healthy subjects who took SAM-e supplements did not have increased plasma homocysteine levels. Instead, the SAM-e supplementations was linked to an increase of co-factors in homocysteine metabolism, therefore having the potential to reduce total homocysteine levels [16].

SAM-e for Liver Disease

Most SAM-e is produced in the liver, and this may be because SAM-e has a huge role to play in protecting the liver against damage and disease.

A meta-analysis of SAM-e supplementation in liver disease concluded that SAM-e can reduce some liver enzymes that are characteristically elevated in liver disease. However, the results also suggested that SAM-e was NOT more effective than common medications for liver disease. It may play a role as a co-therapy but should not be used in place of conventional treatment [17].

A study in 2011 showed that SAM-e could improve the effects of medical treatment for viral hepatitis C in patients who were previously not responding to treatment [18].

On the flipside, SAM-e doesn’t appear to be an effective treatment for alcohol liver disease. A 24 week double-blinded, randomised, placebo-controlled trial showed that SAM-e supplementation was no more effective than taking placebo for the treatment of alcoholic liver disease. Abstinence was shown to be the most effective treatment.

How to Take SAM-e Supplements

Here’s the rub: SAM-e has poor bioavailability. When taking an oral SAM-e supplement, it must be metabolized through first-pass liver detoxification – and this is where a lot of it is destroyed before it can move into the general circulation. Of course supplement companies account for this by stuffing a lot of SAM-e into each product. However, the amount of SAM-e that makes it into the blood stream will always differ between individuals. If possible, choose a high absorption formula such as Actif 40x Absorption SAM-e to ensure the highest results.

SAM-e dosage

Starting with a dose of 200mg per day and working up to 400mg – 600mg per day is generally considered to be safe and effective for most people. Speak to your practitioner for personalized dosage advice.

 

References

[1] Moore, L. D., Le, T., & Fan, G. (2013). DNA Methylation and Its Basic Function.Neuropsychopharmacology, 38(1), 23–38. http://doi.org/10.1038/npp.2012.112

[2] Lozano-Sepulveda, S. A., et al. (2016) S-adenosyl-L-methionine modifies antioxidant-enzymes, glutathione -biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells. World J Gastroenterology, 22:14, 3746- 3757. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814737/

[3] 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 Oncology, 1(2), 373–378. http://doi.org/10.3892/mco.2012.53

[4] 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 Genomics, 46(17), 617-623. https://www.ncbi.nlm.nih.gov/pubmed/25180283

[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: http://doi.org/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 Psychiatry, 4, p. 38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535560/

[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: https://doi-org.ezproxy.endeavour.edu.au/10.1016/j.euroneuro.2008.08.004

[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.   https://www.researchgate.net/publication/276488559_A_Prospective_Open-Label_12_Week_Trial_of_S-adenosylmethionine_in_the_Symptomatic_Treatment_of_Alzheimer’s_Disease

[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 Disease, 13(1), 67-70. https://www.ncbi.nlm.nih.gov/pubmed/18334758

[10] Jacobsen, S., et al. (1991) Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol 20:4, 294–302.  https://www.ncbi.nlm.nih.gov/pubmed/1925418

[11] O’Malley, P. G., et al. (2000) Treatment of fibromyalgia with antidepressants: a

meta-analysis. J Gen Intern Med, 15:9 , 659–666. https://www.ncbi.nlm.nih.gov/pubmed/11029681

[12] 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.  https://www.ncbi.nlm.nih.gov/pubmed/9225876

[13] Sarac, A. J. & Gur, A. (2006) Complementary and alternative medical therapies in fibromyalgia. Curr Pharm Des, 12:1, 47–57. https://www.ncbi.nlm.nih.gov/pubmed/16454724

[14] 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 : JGC, 11(1), 32–38. http://doi.org/10.3969/j.issn.1671-5411.2014.01.007

[15] Obeid, R. (2013). The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway. Nutrients, 5(9), 3481–3495. http://doi.org/10.3390/nu5093481

[16] 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 Medicine, 15(5), 523–529. http://doi.org/10.1089/acm.2008.0402

[17] 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 ONE, 10(3), 1-17. http://doi.org/10.1371/journal.pone.0122124

[18] 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. Gastroenterology, 140(3), 830–839.e3. http://doi.org/10.1053/j.gastro.2010.09.010.

[19] Medici, V., et al. (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. https://www.ncbi.nlm.nih.gov/pubmed/22044287