SAMe (S-adenosyl-methionine) Supplements Review
Choose the Best SAMe
Supplement. CL Tests Reveal Big Differences in Quality and Cost.
Medically reviewed and
edited by Tod Cooperman, M.D. 
Last Updated
: 07/13/2021 | Initially Posted:
01/16/2016
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Table of Contents
Summary
·
What is SAMe? SAMe is a compound which naturally
occurs in the human body (see What It Is).
·
Health benefits of SAMe: As a supplement, it has two major uses
(see What It Does).
·
It is effective as a treatment for osteoarthritis and associated
joint pain, stiffness, and inflammation. It may take longer to work than
leading anti-inflammatory drugs but the benefit seems to last longer with fewer
side effects.
·
It is an effective antidepressant in treating major depression
and may be particularly useful for people who do not respond to prescription
treatment.
·
How to choose a SAMe product: Choose SAMe products carefully because
it is an expensive ingredient (companies may put in less than listed) and is
sensitive to breakdown if exposed to heat or moisture. Look for a product
packaged in a blister pack (see ConsumerTips™).
Generally, it should also have an enteric-coating to protect it from
degradation by stomach acids which can render it ineffective. (See Quality Concerns)
·
What did CL's tests of SAMe find? Among the 10
products selected by CL for testing, one contained only 76.5% of its
listed SAMe and provided an unusually small dose. (See What CL Found).
·
How much SAMe should I take? Daily dosage shown to be effective in
clinical trials ranges from 800 mg to 1,600 mg of SAMe (See ConsumerTips™ for
details).
·
Best SAMe supplements: See Top Picks for
products which passed testing, were enteric coated, and provided SAMe at lowest
cost. All of these are packaged in blister packs for stability.
·
SAMe safety and side effects: SAMe should not be used by people with
bipolar disorder (See Concerns and Cautions for more
information.)
What It Is:
A
naturally occurring compound, SAMe (also known as SAM-e, S-adenosyl-methionine,
or S-adenosyl-L-methionine) is found in every cell in the body, where it's
manufactured from the essential sulfur-containing amino acid methionine.
Protein-rich foods are sources of this amino acid.
What It Does:
SAMe assists the body in producing a wide range of compounds,
including neurotransmitters (such as dopamine and serotonin) and cartilage
components (such as glycosaminoglycans). When natural SAMe levels are low,
supplements may facilitate the production of these compounds.
Osteoarthritis
SAMe, typically at a dose of about 1,200 mg per day, has been shown to be
effective as a treatment for osteoarthritis of the knee, hip,
hand and spine and associated joint pain, stiffness, and inflammation. Several
studies suggest that SAMe is about as effective as many of the leading
anti-inflammatory drugs -- it may take longer to work but the benefit seems to
last longer and has fewer side effects (Kim, Clin Ther 2009, Najm,
BMC Musculoskelet Disord 2004, Domljan, Int J Clin Pharmacol Ther Toxicol 1989, Muller-Fassbender, Am J Med 1987, Caruso, Am J Med 1987).
Depression
SAMe is one of the most studied natural therapies for treating major depression,
for which it appears to be as effective as older medications but it is of
marginal value relative to serotonin reuptake inhibitors.
Several studies have
shown that it is as effective as tricyclic antidepressants in treating major
depression (Delle Chiaie, Am J Clin Nutr 2002; Salmaggi, Psychother Psychosom 1993; Kagan, Am J Psychiatry 1990).
One study (Papakostas, Am J Psychiatry 2010 clarified
in Fleish, Am J Psychiatry 2010) found that SAMe
may also be helpful to patients with major depressive disorder who did not
respond to prescription treatment with a serotonin reuptake inhibitor (SRI). In
the study, 800 mg of SAMe was given twice daily (a total daily dose of 1,600
mg) along with an SRI for six weeks: 46.1% of patients receiving the
combination benefited, versus 35.8% receiving an SRI and a placebo supplement.
The results suggest that SAMe may be an effective and safe adjunctive treatment
for SRI non-responders. In contrast, a lower daily dose
of SAMe (800 mg -- plus 500 mcg of folinic acid and
200 mcg of vitamin B12, given in two divided doses daily) did not improve
symptoms more than placebo in men and women in Australia with major depressive
disorder who were taking antidepressant medication (including selective
serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake
inhibitors (SNRI), selective noradrenergic reuptake inhibitors (NaRI), tetracyclics (mirtazapine)
or 5-HT2c antagonists (agomelatine)) (Sarris, Eur Neuropsychopharmacol
2018). The same dose of SAMe and B
vitamins given to 41 men and women (average age 44) with major depressive
disorder who were not taking antidepressant medication resulted in a slight,
but statistically significant improvement of symptoms in those who began the study
with the mildest form of major depression, but there was no
improvement in those with moderate to severe forms of major depression. Seven
of the participants who took SAMe reported experiencing a strange taste in the
mouth (which was not reported by anyone taking the placebo) but the frequency
of other adverse events such as headache and abdominal discomfort were similar
between the groups (Sarris, Psychopharmacology (Berl) 2019).
Parkinson's disease
SAMe seems to reduce depression scores in people with Parkinson's disease who
have major depression disorder. One small study among 21 people with
Parkinson's disease and depression found that taking 400 mg of oral SAMe twice
daily while also receiving 200 mg of SAMe intramuscularly for 30 days improved
depression symptoms compared to placebo, although motor symptoms were unchanged
(Carrieri, Curr Ther Res 1990). Another small, open-label
study among 11 people with Parkinson's disease and depression found that taking
800 to 3,600 mg of SAMe daily for 10 weeks improved depression symptoms (based
on the Hamilton Depression Scale) by at least 50% in all but one person. While
there was no significant change in Parkinson's disease symptoms based on the
Unified Parkinson's Disease Rating Scale, eight people reported feeling
increased "on" time (i.e., their symptoms felt well controlled by
their Parkinson's medication), and five people reported fewer and less severe
dyskinesias (involuntary movements). The results of this study are limited by
the lack of a control group (Di Rocco, Mov Disord
2000).
Other conditions
Other potential applications of SAMe include the treatment of fibromyalgia,
liver disease, AIDS-related myelopathy, and attention deficit-hyperactivity
disorder (ADHD) in adults.
There is interest in SAMe for nonalcoholic fatty liver
disease (NAFLD), based on speculation that altered levels of SAMe in the liver
may be associated with progression from fatty liver to nonalcoholic
steatohepatitis (NASH), a more serious condition marked by ballooning of liver
cells. Laboratory research using an animal model of NASH found that
supplementing with SAMe helped protect against liver injury (Noureddin, Exp Biol Med (Maywood) 2015).
However, preliminary unpublished research in Europe among people with NASH
found that SAMe, taken in doses of 1,000 mg, 1,500 mg, or 2,000 mg in two
divide doses daily for six weeks did not improve liver enzyme
levels or markers of fibrosis compared to baseline (Protocol No. M13-397).
For information about
other supplements for osteoarthritis see the Joint Supplement Review (covering
glucosamine, chondroitin, and MSM products). Other supplements used to prevent
or treat depression are St. John's Wort, 5-HTP, and Vitamin D.
Quality Concerns and
Tests Performed:
SAMe is an expensive ingredient, so experts have been concerned
about the actual quality and quantity of SAMe in supplements. Another concern
is that SAMe is very susceptible to heat and moisture, both of which can cause
it to degrade resulting in less ingredient than what's stated on the label.
Many manufacturers will enteric coat SAMe pills and/or package the product in
blister packs as a way to protect products from degrading throughout their
shelf-life.
SAMe can also be
destroyed by stomach acid. The same enteric coating used to protect the product
on the shelf can also help protect the product from stomach acid so that it can
be absorbed in the intestines.
A stabilizing molecule is
always added to SAMe products, often making it unclear as to the true weight of
active SAMe because the weight of the inactive stabilizer may be included in
the labeled amount. In fact, when first tested by ConsumerLab.com in 2000,
nearly half of the products were found to contain significantly less SAMe than
they claimed. This has improved over time.
No government agency is
responsible for routinely testing SAMe supplements for their contents or
quality. However, ConsumerLab.com independently evaluated several leading SAMe
products to determine whether they contained the SAMe amounts stated on their
labels. All tablets and caplets were also tested to be sure that they would
properly disintegrate ("break-apart") and, if enteric coated,
properly released their ingredients after withstanding one hour in a simulated
gastric environment. (See How Products Were
Evaluated for information on testing methods and standards.)
The majority of products
tested in this Review are from popular and, generally, well-established brands,
as we are guided in our product selection by our readers' interests in brands
as conveyed in our annual survey. However,
it was brought to our attention in March, 2020 that an established brand, NOW
Foods, conducted its own tests earlier that month of selected competing
brands of SAMe sold on Amazon.com. These brands are generally not popular among
our readers. Those tests suggested that products from several companies (BoostCeuticals, Metaphormine,
aSquared Nutrition, NasaBe'Ahava,
Healthy Way, Naturetition, Mental Refreshment, monoHerb, and Superior Health) contained only 8% to 53%
of their listed SAMe, with one having no detectable amount. ConsumerLab.com was
not involved in this testing and cannot vouch for its accuracy but was made
aware of the results from an online merchant, iHerb.com, which is an
established online vendor that posted the results as a PDF on
its own site.
What CL Found:
Of the 10 SAMe supplements selected for testing by
ConsumerLab.com, all but one passed our tests and quality criteria. An
additional four products passed the same testing through ConsumerLab.com's
voluntary Quality Certification Program.
The product that failed to pass testing was Cellfood
SAM-e Liquid Formula. It claimed to provide 72 mg of SAM-e per 20-drop
serving, but only contained 55.1 mg — 76.5% of the amount claimed. In addition
to falling short of its claim, the suggested daily serving of SAMe is far
smaller than in most other products (200 mg or more per pill) and the daily
dose found effective in clinical studies (at least 400 mg). The labeling
on Cellfood is also inconsistent:
The Supplement Facts panel shows a "serving" to be 20 drops, but the
"Suggest usage" section recommends taking 10 drops two times daily —
indicating that a "serving" should actually be 10 drops.
Interestingly, in ConsumerLab.com's tests of SAMe
supplements in 2011, one of the two products for human use which failed testing
was also a liquid Maxam Nutraceutics SAMe --
which did not contain any detectable SAMe; the other was an enteric tablet (Integrative
Therapeutics Vitaline SAMe 200 mg) which, similar
to Cellfood, contained only
three-quarters of its listed SAMe.
All other products were enteric coated tablets, except for Designs For
Health SAMe which used regular vegetarian capsules. This may be a
problem due to the sensitivity of SAMe to stomach acid.
Among the products which were Approved in testing, all listed either 200 mg or
400 mg of SAMe per tablet, caplet or capsule. The suggested total daily
dose ranged from 200 mg to 1,600 mg. With such a wide range, it is important
that you know the dosage that is appropriate for you (see ConsumerTips™ for
dosage information).
Top Picks:
To find
superior value, ConsumerLab.com calculated the cost to obtain 400 mg of SAMe
from each of the Approved products. The product with the lowest cost was Nature's
Trove SAMe 400 mg at just 45 cents per enteric-coated caplet,
making it our Top Pick for SAMe. It was followed in price
by Swanson Ultra High Potency SAMe (400 mg per tablet) at 51
cents and Vitamin Depot Double Strength SAM-e at 57
cents. Doctor's Best Double-Strength SAMe 400 and Vitacost SAM-e were close behind at 63
cents each. All four of these come packed in blister packs, which may be
important for stability (to avoid exposure to moisture).
The cost of getting 400 mg of SAMe was much more from some products, with the
highest cost being $3.59 from Nature's Sunshine Sam-e (200 mg
per tablet, $1.80 per tablet).
Test Results by Product:
Listed
alphabetically below are the test results for 14 SAMe products. ConsumerLab.com
selected ten. Four additional products (each indicated with a CL flask) are
included for having passed the same testing through ConsumerLab.com's
voluntary Quality Certification Program.
Shown for each product is the labeled amount of SAMe per tablet as well as the
suggested serving size and the calculated cost to obtain 400 mg of SAMe. The
full list of ingredients is available for each product by clicking on the word
"Ingredients" in the first column. Products listed as "Approved"
met their label claim for SAMe, met FDA labeling requirements and were able to
break apart properly.
|
RESULTS OF CONSUMERLAB.COM TESTING OF SAMe SUPPLEMENTS |
|||||||
|
Product Name, Amount
of SAMe per Unit, Serving Size, and Suggested Daily Serving on Label |
Claimed Amount and
Form of SAMe Per Suggested Daily Serving on Label |
--TEST RESULTS-- |
Cost for Daily
Suggested Serving on Label |
||||
|
OVERALL RESULTS: |
Contained Listed
Amounts of SAMe |
Did Not Exceed
Contamination Limits for Degradation Products |
Disintegrated
Properly |
||||
|
|
72 mg |
NOT |
Found only 55.1 mg daily
(76.5% of listed amount) |
|
NA |
$1.30 |
|
|
|
1,200 mg |
APPROVED |
|
|
|
$2.77 |
|
|
|
200 mg |
APPROVED |
|
|
NA |
$0.85 |
|
|
|
400 mg |
APPROVED |
|
|
|
$0.632 |
|
|
|
800 mg to 1,600 mg |
APPROVED |
|
|
|
$2.60-$5.20 |
|
|
|
400 mg |
APPROVED |
|
|
|
$1.33 |
|
|
|
200 mg to 400 mg |
APPROVED |
|
|
|
$1.80-$3.59 |
|
|
|
400 mg |
APPROVED |
|
|
|
$0.45 |
|
|
|
200 mg to 400 mg |
APPROVED |
|
|
|
$0.49-$0.98 |
|
|
|
400 mg to 1,600 mg |
APPROVED |
|
|
|
$1.15-$4.61 |
|
|
|
400 mg |
APPROVED |
|
|
|
$0.80 |
|
|
|
400 mg to 1,600 mg |
APPROVED |
|
|
|
$0.51-$2.05 |
|
|
|
400 mg |
APPROVED |
|
|
|
$0.63 |
|
|
|
1,200 mg |
APPROVED |
|
|
|
$1.70 |
|
|
|
|||||||
|
Unless otherwise noted, information about the products
listed above is based on the samples purchased by ConsumerLab.com (CL) for
this Product Review. Manufacturers may change ingredients and label
information at any time, so be sure to check labels carefully when evaluating
the products you use or buy. If a product's ingredients differ from what is
listed above, it may not necessarily be of the same quality as what was
tested. |
|||||||
|
Copyright ConsumerLab.com, LLC, 2016. All rights reserved.
Not to be reproduced, excerpted, or cited in any fashion without the express
written permission of ConsumerLab.com LLC. |
|||||||
ConsumerTips™:
Forms
SAMe comes in different forms, depending on the compound used to stabilize it
and prevent degradation. These compounds include tosylate,
disulfate tosylate, disulfate ditosylate, and 1,4-butanedisulfonate (Actimet™). They're usually written immediately after SAMe's
chemical name. Because these added compounds weigh as much as the SAMe molecule
itself, a tablet containing 200 mg of "S-adenosyl-methionine disulfate tosylate," for example, contains only 100 mg of SAMe.
Most, but not all, labels make this clear. An accurate ingredient listing for
SAMe in the Supplement Facts panel on a product should exclude the stabilizing
compound, as does the dosage information below.
There is no evidence to suggest one form is more beneficial than another,
although most supplements in the U.S., and all of the supplements in this
review, contain the tosylate, disulfate tosylate, or disulfate ditosylate
form. One in-vitro study found the 1,4-butanedisulfonate form did not stimulate
brain cells when compared to the free form of SAMe (s- adenosyl-l- methionine
with no stabilizing compounds attached) (Travagli, Euro J Pharmacol
1994). However, this study was performed in isolated brain
tissue, not in humans. A clinical study in people with depression found a dose
of 1600 mg of the 1,4-butanedisulfonate form of SAMe (providing 800 mg of SAMe
daily) for 6 weeks improved symptoms of depression as well as 50 mg the
tricyclic antidepressant imipramine (Chiaie, Am J Clin Nutr 2002) a- similar to the antidepressant
effect found for SAMe supplementation in general (Bressa, Acta Neurol Sc
and Suppl 1994). Most studies on SAMe for osteoarthritis
appear to use the tosylate, disulfate tosylate, or disulfate ditosylate
form.
SAMe, homocysteine and B vitamins — What's the
connection?
SAMe is converted into homocysteine in the body. There has been concern that
taking SAMe supplements may raise homocysteine levels — elevated levels of
which are a risk factor for cardiovascular disease. However, short term studies
with daily doses of SAMe of up to 1,600 mg have not been shown to increase
homocysteine levels (Thompson, J Altern Complement Med
2009; Goren, Pharmacotherapy 2004).
One way the body eliminates homocysteine is by converting it into the
antioxidant glutathione in a process that requires B vitamins such as B6, B12
and folate (Obeid, Nutrients 2013).
For this reason, supplementing with B vitamins is sometimes recommended when
taking SAMe. However, based on the studies noted above showing no increase in
homocysteine levels following short-term SAMe supplementation, it would appear
that, as long as you have an adequate intake of B vitamins from your
diet, supplementing with B vitamins should not be necessary.
Storage
Because SAMe is very susceptible to degradation when exposed to moisture, it is
often sold in blister packaging in which each tablet is individually sealed.
This protects the pills. Products sold in blister packs are noted in the table
above -- last column. Be careful with pills sold in bottles: keep them out of
moisture and heat; keep the bottle sealed; and if they come with a desiccant
(drying) pack in the bottle, keep the pack in the bottle to protect the pills.
How to take
It is generally recommended that SAMe be taken on an empty stomach to increase
absorption, although this does not appear to be well documented. If SAMe causes
nausea or stomach upset, take it with food, or take an enteric-coated product
-- as it is less likely to break down in the stomach, but rather, in the
intestine, where SAMe is absorbed. You can also try taking smaller, divided
doses.
Dosage
Generally recommended daily doses of SAMe range from 400 to 1,600 mg, depending
on the condition, its severity, and course of treatment.
Osteoarthritis — most studies found that 1,200 mg of SAMe was as effective as
leading anti-inflammatory treatments in relieving joint pain (Kim, Clin Ther 2009; Najm,
BMC Musculoskelet Disord 2004; Muller-Fassbender, Am J Med 1987). One study
found that taking 1,200 mg the first week, followed by 800 mg thereafter was as
effective as taking naproxen (Aleve) for the relief of knee pain (Domljan, Int J Clin Pharmacol
Ther Toxicol
1989). Losing weight and switching from high-impact to
low-impact sports are also recommended for people with osteoarthritis.
Depression — doses ranging from 400 to 1,600 mg per day have been used. Several
studies have used 1,600 mg daily of SAMe alone (Delle Chiaie, Am J Clin Nutr 2002); Salmaggi, Psychother Psychosom 1993, Kagan, Am J Psychiatry 1990)
or as an adjunct to treatment with a serotonin reuptake inhibitor (SRI) (Papakostas, Am J Psychiatry 2010).
Fibromyalgia — 800 mg per day has been used.
Liver disease — higher doses of 1,200 mg to 1,600 mg per day have been used for
treatment.
After starting SAMe supplementation, improvements may take anywhere from a few
days to five weeks to become noticeable. The doses noted above are for SAMe
taken orally. SAMe also has been taken by injection under medical supervision.
Concerns and Cautions:
SAMe is
generally considered safe when taken in appropriate doses, but be aware that it
may occasionally cause nausea and stomach upset. Taking
enteric-coated products, reducing the SAMe dosage, or taking it with meals may
reduce these adverse effects. A strange taste in the mouth has
also been reported with SAMe supplementation (Sarris, Psychopharmacology (Berl)
2019).
A suspected serotonergic reaction (which can cause symptoms
such as agitation, sweating, high body temperature and diarrhea) leading to
hospitalization was reported in an individual taking 800 mg of SAMe daily in
addition to antidepressant medication. However, the reaction resolved quickly
and was not confirmed as serotonin syndrome (Sarris, Eur Neuropsychopharmacol
2018).
Higher doses of SAMe (1,600 mg per day) have been reported to cause drowsiness in
some people (Arnold, Eur Neuropsychopharmacol
2005).
Individuals with bipolar (manic/depressive) disorder should know that SAMe
could trigger a manic phase. People taking standard
antidepressants, including MAO inhibitors, SSRIs, and tricyclics should not
take SAMe except on a physician's advice. Also, SAMe might help relieve the
side effects of levodopa treatment (for Parkinson's disease) but it might also
reduce its effectiveness over time. SAMe products aren't likely to help severe
osteoarthritis where cartilage has worn down so much that bones rub against
bones.
To further assist consumers, ConsumerLab.com licenses its flask-shaped CL Seal
of Approved Quality (see The CL Seal) to manufacturers for use on
labels of products that have passed its testing. ConsumerLab.com will
periodically re-evaluate these products to ensure their compliance with ConsumerLab.com's standards.
+ 12 sources
Information on this site
is provided for informational purposes only. It is not an endorsement of any
product nor is it meant to substitute for the advice provided by physicians or
other healthcare professionals. The information contained herein should not be
used for diagnosing or treating a health problem or disease. Consumers should
inform their healthcare providers of the dietary supplements they take.
Latest Clinical Research Updates for SAMe Supplements
12/14/2019
SAMe
(S-adenosyl-methionine) may help some, but not all, people with major
depressive disorder, according to a recent study. For details, see the What It Does section
of the SAMe Supplements Review. Also see our Top Picks for SAMe.
9/25/2018
SAMe
(S-adenosyl-methionine) may be helpful in depression, although a recent study
suggests that the right dosage can be important. For details, see the What It Does section
of the SAMe Supplements Review. (Also see our Top Picks among SAMe supplements).
Related CL Answers (12)