SAMe (400 mg) 60 Enteric Coated Tablets

Suitable for vegetarians

• Science-based nutrition
• Dietary supplement
• Enhances mood and neural function*
• Promotes joint comfort and mobility*
• Supports liver health and detoxification*

Our Double-Strength SAMe 400 contains 400 mg of active SAMe in each tablet. Doctor's Best utilizes only the highest quality Italian SAMe available on the market. This ensures that you receive the most potent SAMe product with the highest percentage of the active S,S form per serving, bar none.

S-Adenosyl Methionine (SAMe) is derived from the amino acid methionine and is one of the most important methyl donors in the central nervous system. Methylation (donation of methyl groups) is an essential process in ensuring the proper function of a number of organ systems. SAMe is involved in numerous biochemical reactions in tissue including the liver, joints and brain. SAMe is also required for the biosynthesis of critical neurotransmitters and hormones.

Supplementing with SAMe
The manufacturing process of SAMe yields two forms, the S,S and the R,S isomers. The S,S isomer is the active form that mediates biochemical activity in the human body, whereas the R,S form is considered to be biologically inactive. The Italian SAMe used in Double-Strength SAMe 400 is processed to yield the highest available percentage of the active pure S,S form on the market.

SAMe and Joint Function
SAMe may enhance cartilage protection and promote the synthesis of proteoglycans, essential components of connective tissue. Clinical studies show an ability of SAMe to enhance mobility and movement, and promote joint comfort.*

SAMe and Neural Health
SAMe-catalyzed methylation reactions promote the synthesis of neurotransmitters, which have the potential to promote enhanced mood. SAMe may also upregulate the production of phosphatidylcholine, supporting cognitive function.*

SAMe and Liver Function
SAMe enhances liver synthesis of glutathione, an antioxidant. Glutathione promotes detoxification and liver protection. Studies show SAMe may protect liver tissue from injury caused by a number of toxins.*

Individuals using antidepressant medications should consult with their prescribing physician prior to using this product. Individuals diagnosed with bipolar disease or manic depression should avoid supplementing with SAMe. Do not use if pregnant or nursing. May cause gastrointestinal discomfort in a small percentage of people.

Suggested Adult Use: Take 1 tablet daily away from food, or as directed by a health care professional. Do not chew or crush tablet.

Supplement Facts
Serving Size: 1 Tablet
Serving per container: 60 servings
Amount Per Serving                 %DV
S-Adenosyl Methionine                                              400 mg                         †
(from 800 mg of SAM-e tosylate disulfate)
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Other Ingredients: Cellulose gel, methacrylic acid copolymer, compritol 888ATO, talc, triethyl citrate, titanium dioxide, magnesium stearate, mannitol, glycerol palmitostearate,  silica, medium chain triglycerides, sodium starch glycolate, and iron oxide.

Store in a cool, dry place to ensure maximum quality.

Contains nothing other than listed ingredients.

400mg, 60 Enteric Coated Tabs

SAMe (S-Adenosyl Methionine) is a nutrient unequalled for its health benefits. Doctor’s Best Double Strength SAMe 400 and SAMe 200 supply SAMe optimized for potency, stability, and to survive the stomach acid and reach the intestine (where it is absorbed). Doctor’s Best SAMe supplements are the best available anywhere.

SAMe’s remarkable benefits come from its very high energy content, coupled with its unique molecular structure.^1-3 The SAMe molecule’s high energy facilitates its use as an enzyme cofactor. Literally thousands of enzymes use the energy built into SAMe to overcome energy barriers and thereby to power key metabolic pathways.^1-3

SAMe gets its high energy directly from ATP, the body’s most highly energized molecule.⁴ Specialized enzymes react ATP with the amino acid methionine to transfer much of ATP’s energy into the resulting SAMe molecule.^1,2 SAMe’s chemical energy charge is second only to that of ATP itself.

SAMe’s intricate molecular structure amplifies its favorable energy profile. The SAMe molecule provides enzymes with no less than seven different functional groups to power numerous biochemical reactions.^1-4 Researchers have noted that “no part of the SAMe molecule goes to waste.”⁵ SAMe is an essential cofactor for as many as 3,000 human enzymes that between them control a plethora of life processes.^3,4

Potent Promoter of Mood and Cognitive Health

After at least 18 controlled human trials, published over almost four decades, SAMe is clearly proven to promote healthy mood.^5-12 The latest double-blind trial was published in 2010,^7,8 and its findings were so impressive that the journal also published an editorial in praise of SAMe.⁹ This editorial attributed SAMe’s marked mood benefits to its diverse roles in brain metabolism.⁹

SAMe is essential for the healthy metabolism of the major brain transmitters dopamine, serotonin, and norepinephrine.^1,2 SAMe is also essential for the main metabolic pathway that makes PC (phosphatidylcholine), a key cell membrane phospholipid for the nerve cell informational connections (synapses). Myelination—insulation of the nerve cell extensions to optimize their electrical conduction—also requires SAMe.¹³ And SAMe is also essential for the brain to produce melatonin, a hormone that regulates healthy sleep patterns.¹⁴

Individuals who have mood difficulties often also have problems with memory and other cognitive functions. In a 2010 double-blind trial, SAMe supported cognitive health while promoting healthy mood.¹⁰ SAMe supports the metabolism of acetylcholine, a major nerve transmitter that is essential for attention, learning, and memory and for numerous other functions outside the brain.¹⁵ Even as SAMe ameliorates mood difficulties, SAMe also has improved energy levels, as found in two other double-blind trials.^11,12 Optimal SAMe intakes for mood and cognitive support are 800-1600 mg per day, preferably as divided doses taken between meals.

Promotes Joint Comfort and Mobility

A minimum 14 controlled clinical trials prove SAMe is consistently effective for the support of joint comfort and mobility.^5,16-18 In the longest trial, which lasted two years, 97 subjects received SAMe at 600 mg per day for the first two weeks, followed by 400 mg per day for the remaining period.¹⁶ SAMe continued to improve joint health over the entire course of this long trial, and was very well tolerated.

Most of the controlled trials for joint health used SAMe at 1200 mg per day.^5,17,18 Researchers conducting these trials noted SAMe’s relative lack of adverse effects and its capacity to continue improving joint comfort and mobility over the entire period of the trial.^16-18 A 2002 “meta-analysis” of pooled clinical trial data⁵ and a 2011 clinical review¹⁹ both concluded SAMe is a premier joint support nutrient.

The tissues of the working joint have a matrix of collagen and proteoglycans, large fibrous molecular complexes that give the joint structural stability. SAMe’s energized “active sulfur” group supports collagen and proteoglycan formation.²⁰ SAMe’s active sulfur also supports the bio-synthesis of glutathione, cysteine, and taurine, key components of the joint’s antioxidant defenses (and of the liver and the body as a whole).²¹

Protects and Supports the Liver and Intestine

The liver makes most of the body’s SAMe, and itself relies heavily on SAMe for its structural and functional integrity.²² The liver’s SAMe reserves are readily depleted by alcohol consumption,^23,24 or by a variety of chemical toxins.^25-28 In three human trials,^26-28 supplementation with SAMe protected the liver against alcohol or other manmade toxins. These benefits of SAMe are most likely mediated by its support for the liver pathways that make glutathione and the other sulfur antioxidants.²¹

Most of the liver’s glutathione comes ultimately from SAMe.^21-23 The liver is the major organ wherein “active sulfur” from SAMe is fed into the vast web of sulfur pathways that make glutathione and the other sulfur antioxidants.^1,2 These are at the hub of the liver’s considerable detoxication activity, and also provide its major defense against chemical damage.^21-23 Functionally, glutathione status (and therefore liver health) is highly dependent on SAMe: experimental depletion of glutathione causes SAMe to be used up in replacing the glutathione, while repleting SAMe leads to restoration of glutathione reserves.^24,25

In addition to its multifaceted support for liver detoxication, SAMe also supports the liver’s bile secretion function, as reported in at least two clinical trials.^29,30

SAMe also helps keep the colon healthy. The colon normally houses bacteria that produce hydrogen sulfide, which is potentially toxic to biomolecules. The cells that line the colon use SAMe to detoxify hydrogen sulfide.³¹ In a clinical study, difficulties with colon function were linked to low blood levels of SAMe.³²

Methyl Source for Genetic, Epigenetic, and Other Vital Processes

Most of the body’s SAMe goes into “methyl transfer reactions,” which make pervasive contributions to life processes.^1-4 Methyl transfer enzymes use SAMe’s high-energy methyl group (“active methyl”) to produce thousands of biomolecules and subsequently to regulate their functional capacities.

Methyl is in our DNA. Active methyl from SAMe is used to make DNA, to make polyamine compounds that fold the DNA into its  required shapes, to help repair damaged DNA, and to facilitate the “reading out” of DNA to make proteins.^1,2,33,34 Methyl enzymes help ensure DNA is accurately converted into RNA and that in turn, this RNA is efficiently “translated” into proteins.³⁴ SAMe’s active methyl is also used to fine-tune the shapes of proteins, to produce phospholipids that build cell membranes, to make hormones and chemical transmitters, and to manage miscellaneous major and minor biochemical tasks.^1,2,33-35

SAMe’s active methyl is also crucial for the regulation of gene activity using molecules that attach to the DNA (“epigenetic regulation"). Methyl enzymes selectively and precisely “tag” genes with methyl groups, to make these genes active or inactive according to the requirements for a particular cell or tissue.^33-35 Methyl tagging regulates numerous other vital processes, including the functional specialization of cells, the coordination of the different cell types in tissues, the activation of detoxification enzymes, even the programming of reproduction and fetal development.^1,2,33-35

Disruption of the normal methyl patterning in human genes has been documented. Researchers found under-methylation of DNA in a human population (Greenland Inuit) exposed to high levels of pollutant chemicals.³⁶ They suggested that as these environmental pollutants deplete glutathione they could also come to deplete SAMe. The consequent limitation of SAMe availability would limit availability of active methyl and account for the inadequate methyl tagging observed in this population. These researchers expressed considerable concern over the health implications of abnormal DNA methylation.³⁶

SAMe’s deoxyadenosyl group is also energy-activated and has considerable functional overlap with SAMe’s methyl transfer reactions. It has become clear that SAMe’s “active deoxy” is used by more than 2800 “Radical SAMe” enzymes,³ and gives SAMe even further importance for human health.³⁷

Essential For Energy Production by the Mitochondria

In two double-blind trials that involved subjects with energy complaints, SAMe significantly improved energy as well as mood.^11,12 This health benefit from SAMe may be related to its roles as a key nutrient for our microscale energy generators, the mitochondria.

The mitochondria have their own semi-separate metabolic apparatus. They need SAMe to produce their own DNA, RNA, and proteins.³⁹ They also rely on SAMe to make their own supplies of coenzyme Q10 and alpha lipoic acid, other nutrients crucial for energy generation and for their structural protection.

More than 90 percent of the body’s ATP is made in the mitochondria. They have intricate enzyme systems that use oxygen to “burn” our foods and thereby to make ATP.  However, some of this oxygen escapes the mitochondria’s control and spawns potentially harmful oxygen free radicals.³⁸ The mitochondria use glutathione as their core antioxidant for protection against these dangerous “sparks of metabolism.”³⁹ To make sufficient glutathione the mitochondria must have sufficient SAMe. The multifaceted importance of SAMe for mitochondria helps explain how SAMe can enhance energy in the whole body.

Doctor’s Best Double Strength SAMe 400 and SAMe 200 are optimized for SAMe’s S,S molecular form, the form naturally produced in the body. These Doctor’s Best products supply SAMe as the Italian made tosylate disulfate salt, which is also the SAMe compound most extensively used in clinical trials. These premium supplements are prepared as enteric-coated tablets to fully ensure SAMe will survive the stomach acid and reach the intestine (where it is absorbed).

Individuals diagnosed with bipolar disorder (“manic depression”) should avoid SAMe supplementation, as it may aggravate the manic phase.

SAMe should be taken between meals, at least one hour away from food. One or more tablets should be taken once or twice a day, to provide a minimum 200 mg to 800 mg per day of SAMe. Daily intakes up to 1600 mg may be useful, as directed by a competent healthcare professional. Avoid chewing or crushing the enteric-coated tablet, so that it can survive passage through the stomach.

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