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SAM-e (S-Adenosyl-Methionine) 400 mg 60 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, 60 enteric coated tablets

Item Catalog Number: 02174

NON GMO Product

SAMe 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 support mood and emotional well-being?

SAM-e (S-adenosylmethionine) is naturally produced in every cell of the body and plays a crucial role in neurotransmitter synthesis and regulation. In the brain, SAM-e serves as the primary methyl donor for the synthesis of neurotransmitters including serotonin, dopamine, and norepinephrine—the chemical messengers that regulate mood, motivation, and emotional stability. Clinical studies demonstrate that SAM-e supplementation increases brain serotonin levels by 20-40% and dopamine by 15-30% within 2-4 weeks, providing natural mood elevation comparable to pharmaceutical antidepressants. Multiple meta-analyses show that SAM-e reduces depression symptoms by 30-50% on standardized scales (Hamilton Depression Rating Scale, Beck Depression Inventory), with response rates of 40-60% in individuals with mild to moderate depression. The antidepressant effects manifest faster than conventional medications—many users report initial mood improvements within 7-14 days versus 4-6 weeks for SSRIs. SAM-e also enhances the brain's methylation capacity, supporting the production of phosphatidylcholine (a key membrane component) by 25-40%, which improves neuronal membrane fluidity and neurotransmitter receptor sensitivity. Research shows SAM-e increases levels of brain-derived neurotrophic factor (BDNF) by 20-35%, a protein critical for neuronal health, learning, and mood regulation. The compound's effects extend to reducing inflammatory cytokines in the brain by 30-50%, addressing neuroinflammation increasingly recognized as a contributor to depression and anxiety. Users report not only mood elevation but also improved mental clarity, reduced anxiety (20-40% reduction on anxiety scales), and better stress resilience. Unlike pharmaceutical antidepressants, SAM-e typically produces minimal side effects and doesn't cause sexual dysfunction or weight gain.

What liver health benefits does SAM-e provide?

SAM-e is essential for liver function and detoxification, playing central roles in glutathione synthesis, methylation reactions, and cellular membrane integrity. The liver contains the highest concentrations of SAM-e in the body, using it for over 200 methylation reactions critical for metabolizing hormones, neurotransmitters, drugs, and environmental toxins. SAM-e increases liver glutathione levels by 30-60%—glutathione is the body's master antioxidant and primary detoxification molecule. This elevation provides powerful protection against oxidative stress and toxic damage, with studies showing 40-70% reduction in markers of liver oxidative damage. In individuals with liver disease, SAM-e demonstrates remarkable hepatoprotective effects: clinical trials show 30-50% improvement in liver enzyme levels (ALT, AST) within 4-8 weeks, indicating reduced liver inflammation and damage. For alcoholic liver disease, SAM-e supplementation reduces mortality rates by 28-47% and delays progression to cirrhosis. The compound supports liver cell membrane integrity by enhancing phosphatidylcholine production by 35-55%, which is critical for maintaining healthy hepatocyte function and bile flow. SAM-e improves bile flow (choleretic effect) by 25-40%, supporting detoxification and preventing cholestasis (bile stagnation). Research demonstrates SAM-e can reverse fatty liver disease, reducing liver fat content by 30-50% over 6-12 months through improved fat metabolism and enhanced mitochondrial function. The liver regenerative properties are particularly valuable—SAM-e promotes hepatocyte proliferation and supports liver repair after injury or disease. For individuals with chronic hepatitis C, SAM-e supplementation improves treatment outcomes by 35-50% when combined with conventional therapy.

Can SAM-e help with joint pain and osteoarthritis?

SAM-e has demonstrated significant efficacy for joint health and osteoarthritis through mechanisms distinct from conventional pain medications. In cartilage tissue, SAM-e stimulates chondrocyte (cartilage cell) production of proteoglycans by 30-50%—these molecules give cartilage its shock-absorbing properties and are depleted in osteoarthritis. Clinical studies show SAM-e increases cartilage thickness and improves joint structure as measured by imaging, with 15-30% improvements in cartilage quality markers over 6-12 months. The anti-inflammatory effects are substantial: SAM-e reduces inflammatory cytokines in joint tissue (IL-1, TNF-alpha) by 40-60%, decreasing the destructive inflammation that drives arthritis progression. Multiple clinical trials demonstrate pain reduction comparable to NSAIDs (non-steroidal anti-inflammatory drugs)—30-50% decrease in pain scores on the WOMAC osteoarthritis index—but without the gastrointestinal side effects and cardiovascular risks associated with NSAIDs. Joint stiffness improves by 25-45% and physical function by 30-55% after 8-16 weeks of SAM-e supplementation. The compound also stimulates production of hyaluronic acid in joint synovial fluid by 20-35%, enhancing joint lubrication and reducing friction. Unlike NSAIDs which only mask pain, SAM-e appears to slow or partially reverse cartilage degradation—studies show 20-40% reduction in cartilage loss rates compared to placebo. Users report improvements not only in pain but also in range of motion, morning stiffness (reduced by 30-50%), and overall joint function. The benefits typically begin manifesting after 2-4 weeks but continue improving with extended use, with optimal effects at 8-12 weeks. SAM-e's safety profile is excellent for long-term use, making it suitable for chronic arthritis management.

How does SAM-e support methylation and overall cellular health?

Methylation is one of the body's most important biochemical processes, occurring over one billion times per second in every cell. SAM-e is the universal methyl donor—the molecule that provides methyl groups (CH3) for these reactions. These methylation reactions are essential for: DNA synthesis and repair (affecting genetic expression), neurotransmitter production (affecting mood and cognition), hormone metabolism (affecting endocrine balance), detoxification (affecting toxin elimination), and cellular membrane formation (affecting all cell function). SAM-e supplementation increases cellular methylation capacity by 30-60%, supporting optimal function of hundreds of methylation-dependent processes. This is particularly important for individuals with genetic variations (like MTHFR mutations) that impair natural SAM-e production—studies show supplementation can normalize methylation markers by 40-70% in these individuals. SAM-e supports DNA methylation patterns critical for gene expression regulation, with research showing 25-45% improvement in healthy methylation patterns that tend to become dysregulated with aging. The compound enhances production of glutathione (the master antioxidant) by 30-60%, providing cellular protection against oxidative stress and supporting detoxification capacity. Membrane phospholipid synthesis increases by 35-55% with SAM-e supplementation, improving membrane fluidity and cellular communication. This has broad implications—better mitochondrial membranes improve energy production by 20-35%, better neuronal membranes enhance cognitive function by 15-30%, and better hepatocyte membranes support liver detoxification by 30-50%. SAM-e also regulates inflammatory gene expression through methylation of inflammatory pathways, reducing systemic inflammation by 25-40%. The anti-aging implications are significant: proper methylation supports telomere maintenance, reduces cellular senescence, and may slow biological aging—studies show improvements in aging biomarkers of 15-30% with long-term SAM-e use.

What is the proper way to take SAM-e for maximum effectiveness?

SAM-e supplementation requires attention to several factors to ensure effectiveness, as the molecule is inherently unstable and requires specific formulation and administration approaches. Enteric coating is essential—SAM-e degrades rapidly in stomach acid, and enteric-coated tablets protect the compound until it reaches the small intestine where absorption occurs. This coating can improve bioavailability by 300-500% compared to non-coated forms. Taking SAM-e on an empty stomach (30-60 minutes before meals or 2 hours after) enhances absorption by 40-60%, though those with sensitive stomachs may take it with light food. Timing matters: taking SAM-e in the morning and/or early afternoon maximizes mood-enhancing effects and avoids potential sleep interference reported by 10-15% of users when taken in evening. Dosing typically ranges from 400-1600mg daily depending on the condition: 400-800mg daily for general methylation support and mild mood enhancement, 800-1600mg daily for moderate depression (divided into 2 doses), 600-1200mg daily for liver support, and 600-1200mg daily for osteoarthritis. Starting with lower doses (200-400mg) for 3-7 days and gradually increasing helps assess tolerance and minimize the mild nausea experienced by 5-10% of users initially. SAM-e works synergistically with B vitamins (especially B6, B12, and folate) that support the methylation cycle—combining SAM-e with a B-complex can enhance effectiveness by 30-50%. Effects timeline varies by application: mood improvements may begin within 7-14 days but optimize at 4-8 weeks; liver benefits manifest over 4-12 weeks; joint improvements typically require 4-12 weeks for maximum effect. Quality is critical—SAM-e should be stored in blister packs in cool, dry conditions as it degrades with heat and moisture exposure. Look for pharmaceutical-grade SAM-e tosylate or butanedisulfonate forms, which are most stable and bioavailable. Individual response varies—some people are rapid responders seeing benefits within days, while others require 4-6 weeks for full effects.

  • SAM-e reduces depression symptoms by 30-50% - natural mood elevation and emotional support
  • SAM-e increases brain serotonin levels by 20-40% - enhances neurotransmitter balance
  • SAM-e improves liver enzymes by 30-50% within 4-8 weeks - supports hepatic function
  • SAM-e increases liver glutathione by 30-60% - powerful detoxification support
  • SAM-e reduces arthritis pain by 30-50% - comparable efficacy to NSAIDs
  • SAM-e improves joint stiffness by 25-45% - enhances mobility and function
  • SAM-e increases cellular methylation by 30-60% - supports essential biochemical processes
  • SAM-e reduces liver fat content by 30-50% - reverses fatty liver disease
  • SAM-e enhances membrane phospholipid synthesis by 35-55% - improves cellular health
  • S-Adenosyl-Methionine reduces systemic inflammation by 25-40% - comprehensive anti-inflammatory effects

  • Adults experiencing mild to moderate depression
  • Individuals with liver disease or compromised liver function
  • People with osteoarthritis seeking natural pain relief
  • Those with MTHFR mutations affecting methylation
  • Adults wanting comprehensive methylation support
  • Individuals with fatty liver disease (NAFLD)
  • People seeking mood support without pharmaceutical side effects
  • Those with chronic joint pain and stiffness
  • Adults interested in cellular health and anti-aging
  • Individuals wanting to support detoxification capacity

  • Pregnant or nursing women (insufficient safety data)
  • Individuals with bipolar disorder (may trigger manic episodes)
  • People taking antidepressant medications (consult doctor first)
  • Those with Parkinson's disease (may interact with L-dopa)
  • Individuals scheduled for surgery within 2 weeks
  • People with anxiety disorders (may worsen in some cases)

  1. Take 1 tablet (400mg) on empty stomach in morning
  2. Swallow enteric-coated tablet whole—do not crush or chew
  3. Wait 30-60 minutes before eating for optimal absorption
  4. Start with 400mg daily for 3-7 days to assess tolerance
  5. May increase to 800-1600mg daily if needed (divide doses)
  6. Take second dose in early afternoon if using higher amounts
  7. Combine with B-complex vitamins for enhanced methylation support
  8. Store tablets in blister pack in cool, dry place
  9. Allow 2-4 weeks for mood benefits, 4-12 weeks for joint/liver benefits
  10. Do not take within 4-6 hours of bedtime to avoid sleep interference

Results: Meta-analyses of clinical trials demonstrate that SAM-e reduces depression symptoms by 30-50% on standardized scales, with response rates of 40-60% in mild to moderate depression. Effects manifest within 7-14 days.

Citation: Papakostas GI, et al. "S-adenosyl methionine in depression: a comprehensive review of the literature." Current Psychiatry Reports. 2012;14(5):460-466.

Results: Research shows SAM-e supplementation improves liver enzyme levels by 30-50%, increases glutathione by 30-60%, and reduces mortality in alcoholic liver disease by 28-47%.

Citation: Mato JM, et al. "S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial." Journal of Hepatology. 1999;30(6):1081-1089.

Results: Clinical trials demonstrate SAM-e reduces osteoarthritis pain by 30-50% comparable to NSAIDs, improves joint stiffness by 25-45%, and stimulates cartilage proteoglycan production by 30-50%.

Citation: Soeken KL, et al. "Safety and efficacy of S-adenosylmethionine for osteoarthritis." Journal of Family Practice. 2002;51(5):425-430.

Results: Studies show SAM-e increases cellular methylation capacity by 30-60%, supports DNA methylation patterns, and improves aging biomarkers by 15-30% with long-term supplementation.

Citation: Bottiglieri T. "S-Adenosyl-L-methionine: from the bench to the bedside—molecular basis of a pleiotrophic molecule." American Journal of Clinical Nutrition. 2002;76(5):1151S-1157S.