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
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.
-Enhances mood and neural function*
-Promotes joint comfort and mobility*
-Supports liver health and detoxification*
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, and its
findings were so impressive that the journal also published an editorial in praise of SAMe. This
editorial attributed SAMe's marked mood benefits to its diverse roles in brain metabolism.
SAMe is essential for the healthy metabolism of the major brain transmitters dopamine,
serotonin, and norepinephrine. 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. And SAMe is also essential for the brain to produce
melatonin, a hormone that regulates healthy sleep patterns.
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. Even as SAMe ameliorates mood difficulties, SAMe also has improved energy levels, as
found in two other double-blind trials. 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. 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. 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.A 2002 "meta-
analysis" of pooled clinical trial data5 and a 2011 clinical review 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).
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. The liver's SAMe reserves are readily depleted by alcohol consumption,
or by a variety of chemical toxins. In three human trials, 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
Most of the liver's glutathione comes ultimately from SAMe. 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. These are at the hub of the liver's considerable detoxication
activity, and also provide its major defense against chemical damage. 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.
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.
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. In a clinical study, difficulties with colon function were linked to
low blood levels of SAMe.
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. Methyl transfer enzymes use SAMe's high-energy methyl group
("active methyl") to produce thousands of biomolecules and subsequently to regulate their
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. Methyl enzymes help ensure DNA is accurately converted
into RNA and that in turn, this RNA is efficiently "translated" into proteins. 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.
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. 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
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. 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.
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, and gives SAMe even further importance for human health.
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. 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. 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
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.
The mitochondria use glutathione as their core antioxidant for protection against these
dangerous "sparks of metabolism." 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.
Serving Size: 1 Tablet
Serving per container: 60
Amount Per Serving % Daily Value *
S-Adenosyl Methionine 400 mg *
(from 800 mg of SAM-e tosylate disulfate)
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.
Take 1 tablet daily away from food, or as directed by a health care professional. Do not chew or
KEEP OUT OF REACH OF CHILDREN. 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
Does Not Contain: milk, egg, wheat, gluten, corn, soy, sugar, sweeteners, or preservatives
Store in a cool, dry place to ensure maximum quality.