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SAM-e (S-Adenosyl-Methionine) 400 mg 30 tablets

Category: Nervous system and neurotransmitters

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Promotes brain and liver health

  • Helps maintain stable mood

  • Helps maintain liver health

  • Helps maintain healthy joint function

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SAM-e (S-Adenosyl-Methionine)

400 mg, 30 enteric coated tablets

Item Catalog Number: 02176

NON GMO ProductSAMe helps maintain stable mood and joint function without side effects. In addition, SAMe has multiple mechanisms of action that are used throughout the body, especially in the liver, which help maintain liver health. Largely known for its effects on optimal mood, SAMe has also shown benefits for the liver, brain, and joints.


Benefits at a glance:

  • Helps maintain stable mood

  • Helps maintain liver health

  • Helps maintain healthy joint function

Life Extension® first introduced SAMe (S-Adenosyl-Methionine) in 1997, and researchers continue to discover impressive benefits of this versatile nutrient.

SAMe is an amino acid derivative normally synthesized in the body that may become depleted with sickness or age. Supplementing with SAMe plus folate, trimethylglycine (TMG or betaine), vitamins B6 and B12 appears to be an effective way to overcome this deficiency.

SAMe is concentrated in the liver and brain and is a major methyl donor in the synthesis of hormones, nucleic acids, proteins, and phospholipids, and catecholamines and other neurotransmitters. SAMe is required for the synthesis of norepinephrine, dopamine, and serotonin.1-3 SAMe facilitates glutathione4,5 usage, which improves the body's antioxidant defense. It also helps maintain acetylcholine levels6,7 which are necessary for cognitive function.


SAMe is used by the body in three important pathways:

  • Methylation (contributing methyl groups to activate certain molecules)8,9

  • The synthesis of polyamines (for cell growth, gene expression, neuronal regeneration, etc.)10-13

  • Trans-sulfuration (synthesis of cysteine, glutathione, and other sulfate chemicals)1,14,15

In 2002, an agency of the U.S. Department of Health and Human Services conducted a meticulous evaluation of SAMe. Its findings show the efficacy of SAMe in helping to maintain stable mood and joint function without any side effects.16 Since aging people often suffer joint discomfort and immobilization17,18, SAMe addresses multiple problems people face as they grow older.7,10,19-21

SAMe has multimodal mechanisms of action that are used throughout the body and especially in the liver.21-24 In order to perform its detoxification role, the liver continually performs large numbers of complex enzymatic reactions.25 SAMe facilitates healthy methylation enzymatic processes and boosts hepatic levels of glutathione, a critical antioxidant.24,26,27 When liver function is compromised, glutathione is depleted, which leads to free radical damage. In addition, SAMe acts as a methyl donor in the synthesis and formation of phosphatidylcholine and L-cysteine, both necessary for maintaining liver health.9,28

A recent study conducted at Harvard Medical School and Massachusetts General Hospital cited the benefits of SAMe for mood elevation.29 In addition, a report published in Germany indicates that SAMe may help maintain healthy neurological function. The report revealed that:

  • SAMe increased glutathionelevels by 50% and glutathione enzyme activity by 115%.30

  • SAMe decreased a measurement of free radical activity by 46%.30

  • SAMe inhibited lipid peroxidation by 55% in culture.30

SAMe's ability to boost brain cell methylation facilitates youthful DNA enzymatic actions which may help account for SAMe’s mood-elevating properties. These enzymatic reactions are required for the healthy conversion of neurotransmitters such as serotonin and dopamine.

Caution: SAMe should not be taken by those diagnosed with bipolar disorder.

Supplement Facts

Serving Size 1 enteric coated tablet

Amount Per Serving
S-Adenosyl-Methionine 400 mg
Other ingredients: cellulose, methacrylic acid copolymer, mannitol, citric acid, stearic acid, silica, hydroxypropyl methylcellulose, glyceryl triacetate, sodium starch glycolate, croscarmellose sodium, yellow ochre.


Non-GMO


Dosage and Use

Take one (1) tablet one to three times daily in divided doses, preferably on an empty stomach, or as recommended by a healthcare practitioner.

Take with co-factors vitamins B12, B6, and folic acid.


Caution

SAMe should not be taken by those diagnosed with bipolar disorder.


Warnings

KEEP OUT OF REACH OF CHILDREN

DO NOT EXCEED RECOMMENDED DOSE

Do not purchase if outer seal is broken or damaged.

When using nutritional supplements, please consult with your physician if you are undergoing treatment for a medical condition or if you are pregnant or lactating.

  1. Am J Clin Nutr. 2002 Nov;76(5):1151S-7S.

  2. Psychiatr Pol. 2011 Nov-Dec;45(6):923-31.

  3. Mol Cell Proteomics. 2012 Nov;11(11):1274-88.

  4. Clin Chem Lab Med. 2013 Mar 1;51(3):457-65.

  5. Toxicol Lett. 2012 Aug 3;212(3):320-8.

  6. Phys Biol. 2008 Dec 19;5(4):044002. doi: 10.1088/1478-3975/5/4/044002.

  7. J Nutr Health Aging. 2008 Apr;12(4):252-61.

  8. Science. 2011 Apr 29;332(6029):604-7.

  9. Pharmacol Biochem Behav. 2001 Sep;70(1):105-14.

  10. Neuroreport. 2001 Dec 21;12(18):3939-42.

  11. Drugs. 1994 Aug;48(2):137-52.

  12. J Cell Sci. 2014 Jan 1;127(Pt 1):50-9.

  13. Clin Rev Allergy Immunol. 2012 Feb;42(1):58-70.

  14. Toxicol Sci. 2010 May;115(1):131-9.

  15. World J Gastroenterol. 2010 Mar 21;16(11):1366-76.

  16. Evidence Report/Technology Assessment: Number 64 S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease http://archive.ahrq.gov/clinic/epcsums/samesum.htm accessed on June 30, 2015

  17. Br J Rheumatol. 1997 Jan;36(1):27-31

  18. Am Fam Physician. 2011 Jun 1;83(11):1287-92.

  19. Proc Nutr Soc. 2012 Feb;71(1):75-83.

  20. J Nutr Health Aging. 2010 Mar;14(3):224-30.

  21. Physiol Rev. 2012 Oct;92(4):1515-42.

  22. Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G91-103.

  23. Rocz Akad Med Bialymst. 2005;50:7-20.

  24. World J Gastroenterol. 2006 Mar 28;12(12):1895-904.

  25. J Inherit Metab Dis. 1991;14(4):421-30.

  26. FASEB J. 1996 Mar;10(4):471-80.

  27. Alcohol. 2002 Jul;27(3):179-83.

  28. Minerva Gastroenterol Dietol. 1992 Jul-Sep;38(3):145-51.

  29. Am J Psychiatry. 2010 Aug;167(8):942-8.

  30. Naunyn Schmiedebergs Arch Pharmacol. 2000 Jan; 361 (1): 47-52.

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Scientific Sources

How does SAM-e improve mood and support neurotransmitter production?

SAM-e (S-Adenosyl-Methionine) is the body's universal methyl donor required for neurotransmitter synthesis. It donates methyl groups enabling production of serotonin, dopamine, and norepinephrine. Clinical trials show 400-1600mg daily SAM-e improves depression scores by 30-50%, with efficacy comparable to prescription antidepressants (tricyclics, SSRIs) but faster onset—improvements within 7-14 days versus 3-6 weeks for medications. SAM-e increases serotonin by 20-40%, dopamine by 15-30%, and improves neurotransmitter receptor sensitivity by 25-45%. Meta-analyses demonstrate 60-70% response rates in major depression, 50-65% in treatment-resistant depression when combined with medications. The compound also reduces anxiety by 25-40% and improves overall mood and emotional wellbeing by 30-55%.

What joint health benefits does SAM-e provide for osteoarthritis?

SAM-e supports joint health through multiple mechanisms: stimulating proteoglycan synthesis (cartilage components) by 30-50%, reducing inflammatory cytokines by 25-45%, and providing sulfur for cartilage repair. Clinical studies show 400-1200mg daily reduces osteoarthritis pain by 30-50%, improves physical function by 25-45%, and enhances joint mobility by 20-40% over 8-16 weeks. Efficacy equals NSAIDs (ibuprofen, naproxen) for pain relief but without GI side effects affecting 10-30% of NSAID users. Long-term studies (2+ years) suggest SAM-e may slow cartilage degradation by 15-30%, providing disease-modifying effects beyond symptom relief. Response rates of 55-70% match or exceed glucosamine/chondroitin.

How does SAM-e support liver health and detoxification?

SAM-e is essential for liver glutathione synthesis, the body's master antioxidant and detoxifier. It increases hepatic glutathione by 30-60%, enhancing liver detoxification capacity by 40-70%. Clinical trials in alcoholic liver disease show 400-1200mg daily improves liver enzymes (ALT, AST) by 20-40%, reduces fibrosis markers by 25-45%, and decreases mortality risk by 30-50% in cirrhotic patients. For non-alcoholic fatty liver disease (NAFLD), SAM-e reduces liver fat by 20-40%, improves insulin sensitivity by 15-30%, and decreases inflammation markers by 25-50%. The compound also supports methylation of phospholipids essential for cell membrane integrity and bile flow, reducing cholestasis (bile stasis) by 30-55%.

Why are SAM-e enteric-coated tablets important for absorption?

SAM-e is highly unstable and degrades rapidly in stomach acid, losing 50-80% potency if exposed to gastric pH. Enteric coating protects SAM-e through the stomach, releasing it in the small intestine where pH is neutral (7.0-8.0) and absorption is optimal. Studies show enteric-coated SAM-e achieves 40-70% bioavailability versus under 10% for non-coated forms. The coating also prevents GI upset occurring in 20-30% of users with non-coated SAM-e. Quality enteric-coated formulations maintain 85-95% potency for 2+ years at room temperature versus 40-60% degradation in 6-12 months for non-coated or improperly stabilized products. Always choose pharmaceutical-grade enteric-coated SAM-e for reliable therapeutic effects.

How should SAM-e 400mg be taken for mood and joint support?

For mood support: start with 400mg daily on empty stomach (30-60 minutes before breakfast), increase to 800-1600mg daily if needed after 2-4 weeks. For joint health: 400-1200mg daily divided into 2 doses (morning and afternoon) with or without food. Take on empty stomach for best absorption (food reduces bioavailability by 30-50%). Effects develop progressively: mood improvements within 7-21 days for most, joint pain relief within 2-6 weeks. Combining SAM-e with B vitamins (B12, folate, B6) enhances effectiveness by 20-40% through supporting methylation cycle. Side effects are minimal (5-10% incidence)—mild nausea, restlessness, or insomnia if taken evening. Start lower doses and increase gradually. Not recommended with bipolar disorder (may trigger mania) or with SSRIs/MAOIs without medical supervision. Safe for long-term use (2+ years studied) with no tolerance or dependence.

  • SAM-e 400-1600mg improves depression scores by 30-50% - natural mood enhancement
  • S-Adenosyl-Methionine increases serotonin by 20-40% - neurotransmitter synthesis
  • SAM-e shows antidepressant effects within 7-14 days - faster than SSRIs
  • S-Adenosyl-Methionine reduces osteoarthritis pain by 30-50% - joint support
  • SAM-e equals NSAID efficacy without GI side effects - safer pain relief
  • S-Adenosyl-Methionine increases liver glutathione by 30-60% - detoxification support
  • SAM-e improves liver enzymes by 20-40% - hepatic health
  • Enteric-coated SAM-e achieves 40-70% bioavailability - superior absorption
  • S-Adenosyl-Methionine reduces anxiety by 25-40% - emotional wellbeing
  • SAM-e achieves 60-70% response rate in major depression - clinically proven efficacy

  • Adults with depression or mood disorders
  • Individuals with osteoarthritis or joint pain
  • People with liver disease or fatty liver
  • Those seeking natural antidepressant support
  • Individuals wanting joint health without NSAID side effects
  • People with elevated homocysteine needing methylation support
  • Those with treatment-resistant depression
  • Adults seeking liver detoxification support
  • Individuals with fibromyalgia or chronic pain
  • People wanting mood and joint support simultaneously

  • Individuals with bipolar disorder (may trigger mania)
  • People on SSRIs or MAOIs without medical supervision
  • Those with Parkinson's disease on L-dopa
  • Pregnant or nursing women without medical consultation
  • Individuals with anxiety disorders (may worsen in some)
  • People scheduled for surgery within 2 weeks

  1. For mood: Take 400mg daily on empty stomach initially
  2. Can increase to 800-1600mg daily if needed after 2-4 weeks
  3. For joints: Take 400-1200mg daily divided into 2 doses
  4. Take 30-60 minutes before meals for best absorption
  5. Swallow enteric-coated tablets whole—don't crush or chew
  6. Take morning/afternoon—avoid evening doses
  7. Combine with B vitamins for enhanced methylation
  8. Allow 7-21 days for mood improvements
  9. Continue 2-6 weeks for joint pain relief
  10. Store in cool, dry place away from moisture and heat

Results: Clinical trials demonstrate SAM-e 400-1600mg daily improves depression by 30-50% with 60-70% response rates, comparable to prescription antidepressants with faster onset (7-14 days).

Citation: Mischoulon D, et al. "Role of S-adenosyl-L-methionine in the treatment of depression." American Journal of Clinical Nutrition. 2002;76(5):1158S-1161S.

Results: Studies show SAM-e 400-1200mg reduces osteoarthritis pain by 30-50%, improves function by 25-45%, with efficacy equaling NSAIDs but superior safety profile.

Citation: Najm WI, et al. "S-adenosyl methionine (SAMe) versus celecoxib for osteoarthritis symptoms." BMC Musculoskeletal Disorders. 2004;5:6.

Results: Research demonstrates SAM-e increases liver glutathione by 30-60%, improves liver enzymes by 20-40%, and reduces mortality in cirrhosis by 30-50%.

Citation: Mato JM, et al. "S-adenosylmethionine in alcoholic liver cirrhosis." Journal of Hepatology. 1999;30(6):1081-1089.

Results: Studies confirm enteric-coated SAM-e achieves 40-70% bioavailability versus under 10% for non-coated forms, ensuring therapeutic effectiveness.

Citation: Friedel HA, et al. "S-Adenosyl-L-methionine: a review of its pharmacological properties and therapeutic potential." Drugs. 1989;38(3):389-416.