Formulary Forum

Efficacy of the Dietary Supplement S-Adenosyl-L-Methionine

CW Fetrow and Juan R Avila

OBJECTIVE: To review existing published clinical evidence surrounding the dietary supplement SAMe (S-adenosyl-L-methionine).

DATA SOURCES: The majority of information was obtained from primary published literature identified through MEDLINE search
(1966–February 2001). Information was also obtained through secondary and tertiary sources when available.
STUDY SELECTION AND DATA EXTRACTION: All articles identified from data sources were evaluated and all relevant information
included in this review.
DATA SYNTHESIS: The majority of clinical trial evidence surrounds the application of SAMe for various depressive disorders,
osteoarthritis, and fibromyalgia. Sample sizes of these trials and the dose employed have varied considerably. Several reviews and
at least two meta-analyses have examined the available evidence surrounding SAMe in the therapy of depression for trials
completed prior to 1994 and concluded that SAMe was superior to placebo in treating depressive disorders and approximately as
effective as standard tricyclic antidepressants. Much of this information exists in the form of isolated case reports or solitary clinical
trials. SAMe appears to be well tolerated, with the majority of adverse effects presenting as mild to moderate gastrointestinal
complaints. However, it is apparent that this agent is not without risk of more significant psychiatric and cardiovascular adverse
events. Information documenting drug or food interactions with SAMe is very limited.
CONCLUSIONS: Consumers should be instructed to avoid unmonitored consumption of this dietary supplement until sufficient
discussion has taken place with their primary healthcare provider. Although there exists significant potential for therapeutic
application of SAMe, its uncertain risk profile precludes definitive recommendation at this time. Healthcare providers and consumers
should likely temper their enthusiasm for this dietary supplement until sufficient information becomes available.
KEY WORDS: ademetionine, S-adenosyl-L-methionine.

Ann Pharmacother 2001;35:1414-25.

ACPE UNIVERSAL PROGRAM NUMBER: 407-000-01-031-H01

uch advertising, including banners on the Internet, gia. In Europe, SAMe is also commonly known as SAM
M touts the purported beneficial effects of the dietary
supplement S-adenosyl- -methionine (SAMe; also called
L
or ademetionine, and by the name AdoMet in Switzerland.1,2

S-adenosylmethionine). Indeed, this supplement has be- PHARMACOLOGY/PHARMACODYNAMICS

come so famous that it was the focus of a 1999 issue of
Newsweek.1 Despite being essentially unknown in the US
supplement market three years ago, SAMe has risen to be
one of the top 25 dietary supplements in a market of more
than 13 000 others. What makes this particular dietary sup-
plement so popular? Perhaps the myriad of claims sur-
rounding its use have helped. SAMe is being commis-
sioned by proponents as an antidepressant, an antiarthritic,
a nootropic agent, an agent for cholestasis and liver disor-
ders, a treatment for migraines, and therapy for fibromyal-
Author information provided at the end of the text.
First described in 1953 by Cantoni,3 SAMe is naturally
synthesized in the body during the metabolism of methio-
nine to cysteine, taurine, glutathione, and other polyamine
compounds (Figure 1). This biochemical conversion takes
place in the presence of methionine-adenosyl-transferase
and adenosine triphosphate. Subsequent development of a
sensitive and specific assay for SAMe showed that it exists
in varying quantities in mammalian cells. Although syn-
thesized in many cells, including the brain, the majority of
SAMe’s metabolic generation occurs in the liver, where it
uses >70% of dietary methionine.4 SAMe functions as a
primary methyl group (–CH3) donor for a broad range of

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compounds (catecholamines, neurotransmitters, proteins,
membrane phospholipids, fatty acids, nucleic acids, por-
phyrins, choline, carnitine, creatine). After liberation of its
methyl group, SAMe is converted to S-adenosyl-homocys-
teine, a competitive inhibitor of SAMe-mediated methyla-
tion reactions. SAMe-mediated methylation of certain
phospholipids (i.e., phosphatidylethanolamine) and pro-
teins aids in control of the fluidity and microviscosity of
mammalian cell membranes.5 Phosphatidylcholine is one
such membrane-regulating entity produced within hepatic
microsomes by the interaction of SAMe and phosphatidyl-
ethanolamine. Other human cell types have been identified
as being capable of the same biochemical methylation re-
actions. Some debate exists as to whether additional en-
zymes participate in this process.5 SAMe’s interaction with
membrane proteins results in N-methylation of basic res-
idues (i.e., lysine, arginine, histidine) and carboxymethyla-
tion of acidic residues (i.e., aspartate, glutamate).6
SAMe crosses the blood–brain barrier. It has been shown
to increase the concentrations of homovanillic acid and 5-
hydroxyindolacetic acid7 and reduces plasma luteinizing
hormone and serum prolactin concentrations.8 Based on
these and other findings, it has been suggested7,9 that SAMe
may blunt noradrenergic responsiveness while increasing
concentrations of dopamine and serotonin in the central
nervous system. SAMe displays a weak and inconsistent
effect on monoamine oxidase (MAO) type B receptors.10
Whether any or all of these effects play a part in the thera-
peutic application of SAMe supplementation and the de-
sired beneficial response in depression has yet to be deter-
mined.
Figure 1. Methionine metabolism pathway. ATP = adenosine triphosphate; 5-MTHF = 5,10-
methylene tetrahydrofolate.
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The rationale for general therapeutic application of
SAMe stems from the philosophy that exogenous adminis-
tration of SAMe may bring about the restoration of “youth-
ful” levels of this metabolite and thereby induce beneficial
changes in the individual whose problems, at least in part,
are related to a relative deficiency of the compound. Rat
data11,12 suggest that tissue concentrations of SAMe decline
sharply after birth and continue to diminish as the organ-
ism ages, despite the presence of an intact SAMe enzyme-
synthesizing system (methionine-adenosyl-transferase).
Additionally, human data demonstrate that blood concen-
trations in children exceed those of adults.13 Interestingly,
activity of the enzyme that forms SAMe, methionine-
adenosyl-transferase, is diminished in patients with major
depression and schizophrenia, but elevated in those with
mania.14
Pharmacokinetics
In the body, SAMe acts as an unstable intermediate
compound. The first attempt to produce a stable, reliable
oral dosage form was that of a p-toluene sulfate salt form
of the chemical.15 More recently, an enteric-coated oral for-
mulation has been created.16 SAMe has very poor absorp-
tion and bioavailability, supposedly related to a first-pass
effect.17
Subsequently, several studies have evaluated an injectable
formulation. Peak plasma concentrations are attained three
to six hours after oral administration of 400 mg.15 Plasma
protein binding is thought to be ≤5%. In the study by
Loehrer et al.,18 the half-life of endogenous SAMe after
methionine loading ranged from 2.7 to 17
hours (7.1 ± 3.9 h, mean ± SEM) in a small
study of 12 subjects. Half-life of the injectable
formulation is approximately 80–100 minutes.
A single oral dose of SAMe 400 mg exhibited
a half-life of 1.7 ± 0.3 hours (mean ± SEM).18
Volume of distribution of SAMe is reported19
to be approximately 0.4 L/kg. The majority of
SAMe is metabolized by the liver, with 24%
of an administered dose excreted in the feces;
<20% is excreted in the urine.
Clinical Trials
DEPRESSION
The majority of clinical trial evidence sur-
rounds the application of SAMe for various
depressive disorders. Clinical trials of this na-
ture date back as early as 1973.20 In all, almost
40 clinical trials have evaluated the use of
SAMe for therapeutic potential in some kind
of depressive syndrome. Sample sizes of these
trials vary considerably and tend to be small in
number, ranging from as few as seven to as
many as 86 subjects. Additionally, the dosage
of SAMe employed has also varied. Re-
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CW Fetrow and JR Avila

searchers have used either parenteral (range 45– 400 mg/d)
or oral SAMe (1600 mg/d) and/or a combination of the
two. Several reviews and at least two meta-analyses have
examined the available evidence surrounding SAMe in the
therapy of depression for trials completed prior to 1994.21-25
The most recent meta-analysis25 concluded that SAMe was
superior to placebo in treating depressive disorders and ap-
proximately as effective as standard tricyclic antidepres-
sants. Overall, when SAMe was compared with placebo,
the global effect size of SAMe ranged from 17% to 38%,
depending on the definition of a therapeutic antidepressant
response. This average effect size (27.5%) is somewhat
greater than that documented in other meta-analyses for ex-
isting antidepressants.26 Reviews from this period of time
appear to echo the conclusions of Bressa.25
Information from additional clinical trials completed af-
ter the meta-analysis conducted by Bressa25 is available.
Unfortunately, most of these data suffer from some of the
same biases associated with earlier investigational data.
Many studies have been conducted in small numbers of
patients (n < 50); some have used less than ideal study sub-
jects (e.g., alcoholics), several trials had to be conducted
without the use of a placebo control group, many have
been conducted for only four weeks or less, and still others
lacked the appropriate statistical analysis (Table 1).16,27-33
Criconia et al.27 studied 48 patients with major depres-
sion associated with severe physical diseases of varied ori-
gin. The main inclusion criterion for depression was a
baseline score ≥10 on Beck’s Depression Inventory (BDI).
Forty inpatients were treated with intravenous and intra-
muscular injection with SAMe (200 mg at 0800 and 200
mg at 2400) for four weeks. The remaining eight outpa-
tients received 800 mg/d of oral SAMe (400 mg at 0800
and 400 mg at 2400) for four weeks. At trial completion,
the mean score of the group had decreased significantly
(from 28.16 ± 0.43 to 13.43 ± 0.44, mean ± SD; p < 0.01).
Unfortunately, no control group was employed.
Another four-week investigation28 evaluated 40 alco-
holic patients with major depression. The main inclusion
criterion for enrollment was a baseline score of ≥17 on the
Hamilton Rating Scale for Depression (HRSD). Ethanol
ingestion was documented to be at least 150 g/d for six

Table 1. Select Clinical Trials of SAMe in Depression

Reference Patients Dosage Results Limitations

Salvadorini et al. n = 39; outpatients, acute 45–70 mg/d iv/im for 3 wk
HRSD compared with open-label; no
(1980)32 inpatients, chronic inpatients baseline (p < 0.001) placebo control
Carrieri et al. n = 21; Parkinson’s disease 200 mg im + 400 mg po bid vs.
BDI (p < 0.05) small study; unclear
(1990)29 placebo for 4 wk
HRSD (p < 0.01) how dropouts were
handled statistically
Kagan et al. n = 15; major depression 200 mg po initially; titrated to
HRSD significant by randomized, double-
(1990)33 1600 mg/d vs. placebo for 3 wk days 14 and 21 vs. blind, placebo-con-
placebo (p < 0.05) trolled, small
study group
Rosenbaum et al. n = 20; outpatients; one-half 400 mg po initially; titrated to
HRSD (p < 0.001) open-label; small
(1990)16 considered resistant 1600 mg maximum by day 19; compared with baseline study group; no pla-
study period total of 6 wk cebo control
De Vanna and n = 30; major depression 1600 mg/d po vs. imipramine
HRSD parallel group (imipra-
Rigamonti 140 mg/d for 6 wk
HRSA mine–control); simi-
(1992)31
MADRS lar responses seen

ZSRS for both SAMe and
(p ≤ 0.05 for all parameters imipramine in all
and for both treatments) parameters; how-
ever, no statistical
analysis conducted
Salmaggi et al. n = 80; postmenopausal 1600 mg po once daily vs.
HRSD 10 pts. dropped out
(1993)30 placebo for 4 wk
BDI due to lack of com-
(both p < 0.001) vs. placebo pliance
Agricola et al. n = 40 alcoholics; major 200 mg iv + 400 mg po bid daily
HRSD no concurrent pla-
(1994)28 depression for 4 wk after 7-d wash-in period
ZSRS cebo control group;

VAS all comparisons

L/M face scale made against base-
(all p < 0.01); no line measures
change on HRSA
Criconia et al. n = 48; “internal illnesses” 200 mg iv/im bid for inpatients;
BDI no placebo control;
(1994)27 400 mg po bid for outpatients for 4 wk (p < 0.01) compared varying dosage
with baseline forms and dose
strategy; 7 proto-
col violators were
withdrawn

BDI = Beck’s Depression Inventory; HRSA = Hamilton Rating Scale for Anxiety; HRSD = Hamilton Rating Scale for Depression; L/M face scale =
Lorish and Maisiak face scale; MADRS = Montgomery-Asberg’s Rating Scale for Depression; SAMe = S-adenosyl-L-methionine; VAS = Visual Ana-
log Scale; ZSRS = Zung’s Self-Rating Scale for Depression.

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months. Patients who appeared to respond, in terms of the
HRSD, during a seven-day washout phase were excluded
from further study. The remaining patients underwent daily
intravenous administration of SAMe 200 mg and 400 mg
orally twice daily. Patients were evaluated at weekly inter-
vals and required to abstain from alcohol as well as other
concomitant medications. One patient did not complete the
trial due to protocol violation. Average baseline score on
the HRSD decreased significantly (from 69.71 to 22; p <
0.01). Mean treatment scores for the Zung Self-Rating
Scale and the Lorish and Maisiak face scale also improved
significantly (p < 0.01 for both). Significant changes in
these scales were seen at day 14 and continued throughout
the study. No control group was employed in this study.
SAMe was evaluated in depressed patients with Parkin-
son’s disease.29 This study was not included in the meta-
analysis conducted by Bressa.25 This double-blind, ran-
domized, placebo-controlled trial evaluated SAMe 200 mg
intramuscularly and 400 mg orally twice daily in 21 sub-
jects. After a four-week run-in period, patients were ran-
domly allocated to SAMe or placebo. Assessment occurred
at two-week intervals during the 30-day treatment period.
Crossover was done after a two-week washout period. At
the close of the trial, averaged results of scoring for the
HRSD and the BSDI scales favored SAMe treatment over
placebo (p < 0.01 for HRSD and p < 0.05 for BSDI).
Symptoms of parkinsonism were unchanged.
Overall, despite significant limitations in several trials,
there appears to be a reasonable suggestion of potential ef-
ficacy of SAMe therapy for the treatment of depression. It
should be noted that, in some of the trials, common rating
scales used to measure severity of depression (e.g., HRSD,
BSDI) seemed to document improvement in patient symp-
tomatology; however, improvements were not necessarily
to the extent that allowed individuals to return to a com-
pletely normal state of functioning. Depending on the
severity of depression, the therapeutic benefit seen with
SAMe therapy in the clinical trials, despite being statisti-
cally significant compared with controls, may be inade-
quate to completely protect patients from the potential risk
of suicide, especially in patients with severe depression
and those who simply may fail SAMe therapy. Table 1
presents data that are characteristic of some of the clinical
trial evidence surrounding SAMe in depression.
DEPRESSION SECONDARY TO FIBROMYALGIA
Fibromyalgia is estimated to occur in approximately
15% of the general population. At least one-third of pa-
tients with primary fibromyalgia experience depression as-
sociated with their disease.34 Consequently, investigators
have attempted therapeutic trials in patients with fibromyal-
gia in hopes of ameliorating the troublesome symptoms as-
sociated with the disease and improving patients’ quality
of life. At least seven trials have attempted to describe a
role for SAMe in fibromyalgia. In general, SAMe did ap-
pear to reduce tender point pain in several of the studies.
Notably, some of these trials might be criticized for utiliza-
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S-Adenosyl-L-Methionine
tion of subjective measurements and the lack of placebo
controls; however, as suggested from clinical trials in de-
pression, depressive symptoms associated with fibromyal-
gia appeared to respond well to SAMe therapy. Table 235-41
summarizes the data associated with SAMe in fibromyalgia.
OSTEOARTHRITIS
Despite the fact that the exact mechanism through which
osteoarthritis develops is controversial, much discussion
suggests that there exists a mismatch between generative
and degenerative forces that govern cartilage formation.
This irregularity exists, at least in part, because of a mal-
function in proteoglycan synthesis. Proteoglycans are es-
sentially mucopolysaccharides that exist in the extracellu-
lar matrix of connective tissue. One in vitro study42 of SAMe
suggest that it may favorably affect the synthesis of proteo-
glycans, therefore restoring the imbalance that occurs. This
appears to be a concentration-dependent phenomenon,
with optimal increases of both total protein and proteogly-
can production seen at in vitro concentrations of 10 µg/mL
and an inhibitory effect on proteoglycan synthesis seen
with excessive concentrations (100 µg/mL). Treatment
with SAMe for 60 days in this trial42 did not significantly
alter chondrocyte (cartilage cell) proliferation for either os-
teoarthritic or normal human articular chondrocytes.
In contrast, studies43,44 in rabbits have shown that intra-
muscular administration of SAMe significantly improved
the parameters of cell number and cartilage depth in rab-
bits with artificially induced osteoarthritis compared with
placebo, and the presence of SAMe was shown to aid in
the reversal of detrimental effects on fibronectin and pro-
teoglycans induced by tumor necrosis factor alfa. Notably,
the results of other animal studies18,45 have suggested that
SAMe exerts both an analgesic and antiinflammatory ef-
fect. Interestingly, while studying the effects of SAMe in
depression, some of the subjects with osteoarthritis noted
marked improvement in their joint disease.46 This set of
findings and circumstances forms the rationale for its po-
tential use in osteoarthritis.
A rather extensive review46 of the literature surrounding
the utilization of SAMe in osteoarthritis evaluated clinical
trial data published between 1980 and 1987. Information
from 12 studies and more than 22 000 patients was includ-
ed. In these trials, SAMe doses ranged between 400 and
1200 mg/d orally, usually in divided doses, with treatment
courses lasting between three weeks and two years. Con-
clusions developed from this review suggest that clinical
trials thus far provide evidence that SAMe improves both
objective and subjective symptoms of osteoarthritis to a
greater extent than placebo, but to a similar extent as non-
steroidal antiinflammatory drugs (NSAIDs). During com-
parisons of SAMe with various NSAIDs (ibuprofen,47-49
indomethacin,50 naproxen,51,52 piroxicam53), it appears that
the beneficial therapeutic effect may lag behind that of the
NSAIDs at two weeks, but achieves equal efficacy at four
weeks and longer.46-52 Although this review46 summarizes
an impressive array of clinical data from a large number of
■ 2001 November, Volume 35 ■ 1417
CW Fetrow and JR Avila

subjects, 25% of these studies used an open-label design;
these data make up essentially 95% of the study population
information. Also, the author was a researcher affiliated
with the Clinical Research Department of BioResearch
S.p.A. (Liscate-Milan, Italy), manufacturer of one of the
more common brands of SAMe during the 1970s–1980s.
One multicenter investigation49 (not reviewed by Di
Padova46) typifies the kind of evidence seen with parallel-
group trials comparing SAMe and NSAIDs. In this dou-
ble-blind, randomized study, 150 patients between the ages
of 40 and 75 years with osteoarthritis of the hip, knee, or
both were randomized to receive oral ibuprofen 400 mg
three times daily or oral SAMe 400 mg three times daily
for 30 days. Enrollment criteria included a diagnosis of os-
teoarthritis based on clinical symptomatology (i.e., pain,
limited movements) and abnormal joint findings on X-ray.
Patients were assessed by means of pain scores, muscle
rigidity, and patient and physician opinion as to how the
treatment was working. Although an attempt was made to
obtain and evaluate objective parameters (e.g., knee flex-
ion angles, hip adduction, hip abduction), the variability in
the way in which this information was collected prevented
the investigators from being able to use the data. No con-
comitant analgesic or antiinflammatory medications were
allowed during the trial. At baseline, patient demographics
and patient characteristics related to osteoarthritis were
similar in each group.
At trial completion, parameters of pain at rest, loading
pain, night pain, active movement pain, passive movement
pain, and muscle spasm demonstrated improvement over
baseline in each treatment group for the two evaluation pe-
riods (16 and 31 d). In the SAMe group, only the parame-
ter of active movement pain demonstrated improvements
at 31 days that were considered to be significantly favor-
able when compared with improvements seen with ibupro-
fen (p < 0.05). Although both treatments were judged ben-
eficial, neither physician impression nor patient opinion
produced any significant differences for the two treatment
groups. Both agents were tolerated similarly, with only mi-
nor adverse effects noted for each group. This led the in-
vestigators to conclude that SAMe may deserve a role sim-
ilar to that of NSAIDs in the therapy of osteoarthritis.49
More recently, Bradley et al.54 conducted a 28-day trial
in 81 patients with osteoarthritis. This randomized, double-
blind study, one of the few conducted in the US, compared
intravenous SAMe 400 mg/d for five days, then 200 mg
orally three times daily for 23 days with placebo in patients
with osteoarthritis of the knee. The trial was conducted at
two different joint research centers. After randomization,
subjects were evaluated by the Stanford Health Assess-

Table 2. Select Clinical Trials of SAMe in Fibromyalgia

Reference Patients Dosage Results Limitations
Tavoni et al. n = 17 200 mg im qd or placebo for 21 d
pain points and small no. of subjects; 6 withdrew
(1987)35
HRSD with SAMe from study for unknown reasons;
vs. placebo (p < 0.02) abscess developed at injection
site of 2 pts.
Jacobsen et al. n = 44 400 mg po bid or placebo for 6 wk p = NS for BDI, TPS, IMS; subjective measurements; aceta-
(1991)40 disease activity, a.m. stiff- minophen and morphine use
ness, fatigue, mood via allowed
L/M face scale improved
with SAMe vs. placebo
(p ≤ 0.05 for all)
DiBenedetto et al. n = 30 200 mg im at 0800, 200 mg po at 1200, TPS, HRSD improved with TENS used as control group; no
(1993)41 and 1800 vs. TENS for 42 d SAMe vs. TENS placebo control; analgesics per-
(p < 0.01); p = NS for ZSRS mitted; subjective measures
Grassetto and Varotto n = 47 200 mg im qd and 400 mg po bid for
pain points,
HRSD, subjective pain measure (VAS);
(1994)36 6 wk
ZSRS with SAMe no placebo control
vs. baseline (p < 0.01)
Ianniello et al. n = 10 200 mg im qd for 4 wk
pain points,
HRSD, small no. of subjects; investigators
(1994)37
ZSRS with SAMe vs. also evaluated patients with
baseline (p < 0.01) Sjogren’s syndrome; subjective
pain measures (VAS); no placebo
control
Volkmann et al. n = 34 600 mg iv qd or placebo for 10 d VAS, TPS, BDI, MD-Global acetaminophen use monitored but
(1997)39 Assessment (p = NS) allowed; subjective pain mea-
sure (VAS); 4 pts. withdrew be-
cause of adverse reactions
Tavoni et al. n = 30 400 mg iv qd or placebo for 15 d
pain points,
VAS, secondary fibromyalgia; no men-
(1998)38
HRSD,
SED with tion of statistical tests used; no
SAMe vs. placebo; exclusion criteria noted; no mention
(p < 0.0007) of control of analgesic use;
DMARDs and steroids used
concurrently

BDI = Beck’s Depression Inventory; DMARDs = disease-modifying antirheumatic drugs; HRSD = Hamilton Rating Scale for Depression; IMS = isoki-
netic muscle strength; SED = Self Evaluation for Depression; SAMe = S-adenosyl-L-methionine; TENS = transcutaneous electrical nerve stimulation;
TPS = tender point score; VAS = visual analog scale; ZSRS = Zung’s Self-Rating Scale for Depression.

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ment Questionaire (disability and pain scales). Additional-
ly, they were questioned in regard to the duration of joint
stiffness in the morning and overall activity of their arthri-
tis. Patients were assessed for joint swelling and tender-
ness, and a goniometer was used to measure range of mo-
tion. They also were appraised by how quickly they were
able to walk 50 feet.
Beck’s Depression Inventory (BDI) and the face scale of
Lorish and Maisiak were also administered. Throughout the
study, acetaminophen use was allowed, but monitored close-
ly. At baseline, randomization to both centers yielded patient
groups that were unevenly paired. Therefore, the data were
evaluated by each site, rather than as an aggregate. At site A,
the only parameter that resulted in a statistically significant
difference between the two groups was “rest pain.” Interest-
ingly, no significant differences were noted between SAMe
and placebo for the BDI or the face scale, suggesting that
any improvements in joint function were not related to
mood alteration. At site B, only the patient’s estimate of
walking distance tolerance favored SAMe over placebo (p =
0.05). Nonsignificant trends favoring SAMe were explained
by the investigators as possibly being attributed to increased
acetaminophen use in the SAMe group. Adverse events re-
sulted in few dropouts in each group. One SAMe patient did
withdraw from the study because of “nervous symptoms”;
however, the majority of adverse reactions were mild, non-
specific gastrointestinal complaints. The investigators sug-
gested that further investigation with SAMe was warranted
because of benefits observed in this study and in other re-
ports, as well as for the reason that ideal pharmacotherapy
for osteoarthritis is lacking.54
In summary, it appears earlier trial data (pre-1988) and
laboratory work may have supported a role for SAMe in
osteoarthritis, although more recent evidence seems to
place that suggestion in doubt.
GASTROPROTECTIVE EFFECTS
Remarkable results seen in animal studies have often
served as the catalyst for conducting larger, more clinically
relevant human clinical trials with SAMe. One trial55 in
rats has received significant attention in the medical litera-
ture. Thirty male Wistar rats were randomly allocated to
treatment with either SAMe 100 mg/kg (0.2 mL/100 g body
weight) by gastric lavage, misoprostol 100 µg/kg subcuta-
neously, or the vehicles for both agents only 30 minutes
prior to exposure with absolute ethanol. Twenty minutes
after exposure to ethanol, the rats were killed and their gas-
tromucosal surface examined for damage and necrosis.
Breadth and severity of gastrointestinal injury were then
assessed by blinded investigators. Similar study designs
were enlisted with other rats for evaluation of aspirin-in-
duced damage as well as physical stress–induced (immobi-
lization) gastromucosal injury.
At conclusion of the trial, both SAMe and misoprostol
functioned similarly, appearing to protect rodent gastroin-
testinal tissue significantly better than the vehicles used
alone for all three types of gastromucosal injury (p < 0.01
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S-Adenosyl-L-Methionine
for all comparisons). The investigator theorized that the
gastroprotective effect of SAMe was likely related to an in-
crease in the synthesis of nonprotein sulfhydryl compounds
at the gastric level.55 This notion is supported by earlier
work in the same area.56 Aside from an earlier study,57 little
information exists with respect to this effect in humans.
LIVER DYSFUNCTION AND CHOLESTASIS
Effects on catechol O-methyltransferase, glutathione, and
sulfur-containing amino acids in the liver form the basis for
the rationale of using SAMe in liver disease.16,19 Animal stud-
ies58-63 have suggested a potential for hepatoprotection from
various toxins, including carbon tetrachloride, acetamino-
phen, D -galactosamine, ethanol, cyclosporine A, and lead.
Review articles64 have discussed potential benefit with
SAMe supplementation in patients with Gilbert’s syndrome
and hepatotoxicity associated with oral contraceptives.
Mato et al.65 evaluated SAMe supplementation (AdoMet
1200 mg/d orally) in 123 alcoholic patients with cirrhosis in
a randomized, placebo-controlled, double-blind trial. Histo-
logic confirmation of disease was available in >80% of pa-
tients enrolled in the trial. Patients were randomized to re-
ceive either SAMe or placebo for a period of two years. No
significant differences were seen in baseline demographics
between the two groups. At trial termination, when com-
pared with the placebo group, treatment with SAMe pro-
duced an almost 50% reduction in the combined outcome
parameter of overall mortality/liver transplantation (30%
vs. 16%), although this was not statistically significant. On
subgroup analysis (removal of patients with Child Class C
hepatitis), a significant effect was seen favoring SAMe over
placebo in the same parameter (29% vs. 12%; p = 0.025).
The combined parameter of time to death or liver transplan-
tation for this subgroup was also found to be statistically
significant (p = 0.046) favoring SAMe supplementation.
The investigators concluded that long-term treatment with
SAMe may improve survival or delay liver transplantation
for patients with less advanced liver disease.
SAMe was studied66 in a small group of patients with
respect to its ability to relieve intrahepatic cholestasis caused
by pregnancy. This single-blind trial, conducted in Italy,
pursued the therapeutic potential of SAMe in this disorder
because of previously published investigations67-69 in rats
suggesting a possible application in either cholestasis or
cholelithiasis. Theoretical speculation suggests that SAMe,
as a methyl donor, may facilitate inactivation of reactive
estrogen metabolites and/or stimulate membrane phospho-
lipid synthesis, affording protection against estrogen-in-
duced cholestasis.
Eighteen pregnant women with intrahepatic cholestasis
of pregnancy were divided into three groups of six each
and randomized to either intravenous SAMe 200 mg/d, in-
travenous SAMe 800 mg/d, or a placebo (NaCl 0.9%) in-
fusion for 20 days.66 Baseline demographics were similar
between the groups. After 10 and 20 days of therapy, sta-
tistically significant declines in aspartate transaminase,
alamine, serum conjugated bilirubin, and serum total bile
■ 2001 November, Volume 35 ■ 1419
CW Fetrow and JR Avila
acids were noted compared with baseline data (p < 0.05 for
all) for the 800-mg dose of SAMe. These same parameters
were found to be significantly different in favor of the 800-
mg dose when compared with the placebo infusion (p ≤
0.05 for all). This was not the case with the 200-mg dose.
Interestingly, serum alkaline phosphatase values increased
significantly compared with baseline for both doses of
SAMe (at 20 d with 200 mg; p < 0.05; at 10 and 20 days
with 400 mg; p < 0.01 for both). The investigators noted that
it was unclear why this elevation of alkaline phosphatase had
occurred, but concluded that SAMe treatment looked en-
couraging, although additional investigation is warranted.66
Another trial70 conducted in Italy evaluated the use of
the combination of intravenous SAMe 800 mg/d and oral
ursodeoxycholic acid 600 mg/d against either agent used
alone or a control group. Although some aspects of the
study design are questionable (small sample size; methods
of statistical analysis; and use of an undeclared vitamin for
placebo, leading to significant improvement in the placebo
group in some parameters), the investigators concluded
that combination therapy was the most efficacious.
MISCELLANEOUS
SAMe has been postulated to be of some potential bene-
fit in migraine,71 Parkinson disease,29 Alzheimer disease,72
organic brain syndrome,73 epilepsy, HIV-related neurologic
complications, multiple sclerosis, metabolic defects, and
spinal cord disease.63,64 These data were obtained from ani-
mal trials, isolated case reports, or small, solitary clinical
trials which, although intriguing, will require larger-scale
clinical trials before definitive conclusions can be drawn.
Dose–Response Correlation
Del Vecchio et al.21 first attempted to correlate SAMe
serum concentrations with a successful response in de-
pressed subjects. Although their patients showed signifi-
cant improvement on the HRSD (p < 0.05), the investiga-
tors were unable to equate attainment of a particular SAMe
serum concentration threshold with success. However, a
negative linear correlation was found between the HRSD
and SAMe blood concentrations.
This finding was later reproduced7 in a study group of
17 patients. These investigators, however, were able to
show a significantly greater change in the magnitude of
SAMe serum concentrations (p < 0.01) compared with
baseline values (pretreatment 44 ± 25 ng/mL, posttreat-
ment 133 ± 274, mean ± SD; n = 16). Notably, 11 of these
subjects received SAMe supplementation with oral SAMe
800 mg twice daily (Bio-Research, Milan, Italy); six sub-
jects received desipramine 250 mg/d for four weeks. No
mention was made as to which group had a greater impact
on the SAMe serum concentrations. The large deviation
present in the posttreatment data was due to one subject
who experienced an unusually large increase (>1 mg/L).
This was believed to be an aberrant finding and was ex-
cluded from further analysis. At this time, despite the
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availability of a sensitive assay for SAMe, no therapeutic
range for SAMe serum concentrations has been defined.
Adverse Events
In general, SAMe appears to be well tolerated. The ma-
jority of adverse effects, when reported, seemed to be mild
to moderate in nature and of brief duration. Some discus-
sion places the overall incidence of adverse effects at 20%.63
The majority of these tend to be gastrointestinal in nature.
Few patients have withdrawn from trials due to adverse ef-
fects related to SAMe. However, it is apparent that this
agent is not devoid of significant adverse events.
INJECTABLE
In one trial,27 four of 40 depressed patients were noted to
have mild “psychoactivation” after a parenteral SAMe
dose of 200 mg twice daily. Additionally, three patients
showed a moderate psychoactivation or “switch” reaction
to hypomania in a trial by Carrieri et al.29 Despite concern
of this switch phenomenon, the adverse effects exhibited
thus far are of insufficient magnitude to warrant withdraw-
al of SAMe.
In contrast to these data, four of 34 patients with fi-
bromyalgia withdrew from a trial39 due to SAMe-related
adverse events. Two of these patients developed severe
nausea, vomiting, and diarrhea; one required observation
in a hospital. The third patient developed rather intolerable
bowel symptoms, and the fourth developed anaphylaxis
immediately after the first injection. This patient went on
to experience dizziness and cognitive impairment that slow-
ly resolved over two months. In all four of the cases cited,
the adverse event occurred within close proximity to the
time of administration of SAMe.
Significant elevations in serum alkaline phosphatase
were noted in the study66 of pregnant women with intra-
hepatic cholestasis of pregnancy. These changes were un-
able to be explained by the authors and found to be signifi-
cantly different from placebo (p < 0.01). Additionally, tran-
sient pain at the injection site has been reported after intra-
muscular administration of SAMe.27
PARENTERAL AND ORAL
Several studies have used combination SAMe therapy
(intravenous or intramuscular with concurrent oral admin-
istration). Six of 21 depressed Parkinson patients in one tri-
al29 reported adverse effects: three with elation and one
each with heartburn, insomnia, and headache. No adverse
effects were significant enough to warrant withdrawal.
ORAL
Four of eight patients in a study60 of fibromyalgia pa-
tients withdrew because of intolerable adverse effects relat-
ed to administration of oral SAMe at a dose of 800 mg/d
(400 mg twice daily). Seven of the eight experienced gas-
www.theannals.com

trointestinal distress, which led to the withdrawal of three
subjects. The fourth subject withdrew participation due to
SAMe-induced dizziness between weeks 3 and 6 of the
study. Although reported to be a mild effect with the par-
enteral form, the risk of the subjects’ moods becoming ele-
vated to hypomania is still a potential problem with oral
SAMe supplementation.
Contraindications/Precautions
At this time, information surrounding the use of SAMe
in pregnancy or breast-feeding is limited. In a small trial by
Frezza et al.,66 12 pregnant women receiving intravenous
formulations of SAMe were documented to have no unto-
ward effects on their newborns as defined by normal Ap-
gar scores.
Obviously, contraindications would exist for patients
demonstrating hypersensitivity to SAMe or any compo-
nents in the formulation involved. Patients with a history
of bipolar disorder may be at risk of a manic episode when
instituting or continuing supplementation with SAMe. Rat
studies5,74 demonstrate that SAMe supplementation in-
creases plasma corticotropin and glucocorticoid concentra-
tions. If this effect is significant in humans, it may have
implications for patients taking corticosteroids, such as in-
creasing the risk of adrenal crisis after the supplement is
withdrawn after chronic therapy.
HOMOCYSTEINE
Hyperhomocysteinemia is a relatively rare disorder. How-
ever, elevated plasma homocysteine concentrations have
been associated with a dramatically increased risk of throm-
bosis and premature cardiovascular disease.75 Data sur-
rounding the interplay of SAMe supplementation and its
effect on endogenous homocysteine is incompletely under-
stood. Since SAMe participates in the trans-sulfuration
pathway of methionine, there is a theoretical risk with SAMe
supplementation in individuals susceptible to elevated ho-
mocysteine concentrations (i.e., patients with defective or
absent cystathionine β-synthase and/or patients with defi-
ciencies or partial deficiencies of vitamins B6 or B12).
SAMe supplementation might exacerbate hyperhomocys-
teinemia and increase the patient’s risk of thrombosis and
coronary events.
In an initial study,76 the relationship between whole-blood
SAMe concentrations and homocysteine was evaluated in
70 patients with established coronary artery disease and
compared with healthy subjects. As seen in other investiga-
tions, elevated plasma homocysteine concentrations (>12.4
µmol/L for women, >13.3 µmol/L for men) were associated
with reduced concentrations of the active form of folate, 5-
methyltetrahydrofolate (5-MTHF), which is directly in-
volved in homocysteine metabolism. This inverse relation-
ship was identified in 17% of patients with established coro-
nary disease. Notably, 37% of normohomocysteinemic
patients exhibit low 5-MTHF concentrations, suggesting
that insufficient 5-MTHF is not the only cause of elevated
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S-Adenosyl-L-Methionine
homocysteine concentrations. SAMe concentrations were
significantly lower in patients with coronary artery disease
compared with controls (1.4 ± 0.4 vs. 1.8 ± 0.3, mean ± SD;
p < 0.001); however, no correlation was found between
SAMe concentrations and homocysteine or 5-MTHF. These
initial data led investigators to presume that SAMe supple-
mentation might be a protective factor against the develop-
ment of coronary disease related to hyperhomocysteinemia.
In a follow-up study,15 methionine loading was examined
with respect to its effects on plasma SAMe and S-adenosyl-
homocysteine. Twelve healthy subjects were administered
methionine as a single dose (0.1 g/kg in 200 mL of orange
juice) after a 12-hour fast. Serial blood collections revealed
that homocysteine concentrations increased over fourfold
(8.0 ± 1.3 to 32.6 ± 10.3 µmol/L, mean ± SD; p < 0.001)
compared with baseline. Similarly, methionine loading pro-
duced increases in S-adenosylmethionine of more than six-
fold (37.9 ± 25 to 240.3 ± 109.2 nmol/L, mean ± SD; p <
0.001). As seen in the previous trial,76 5-MTHF concentra-
tions declined significantly (23.2 ± 7.2 to 13.1 ± 2.9
nmol/L, mean ± SEM; p < 0.01), returning to baseline after
approximately 24 hours.18
One explanation forwarded by the investigators was that
elevated SAMe concentrations might lead to an allosteric
inhibition of 5,10-methylenetetrahydrofolate reductase,
preventing conversion of tetrahydrofolate to the more ac-
tive form of 5-MTHF. This would, in turn, promote eleva-
tions in homocysteine concentrations by eliminating one
mechanism through which homocysteine would normally
be converted to methionine (Figure 1). Additional data
from this same group of Swiss scientists add to the contro-
versy.2 The effect of a single oral dose of SAMe 400 mg
on plasma concentrations of 5-MTHF and homocysteine
was studied in a group of 14 healthy subjects. Although
SAMe concentrations increased significantly (38 ± 13.4 to
361.8 ± 66.4 nmol/L, mean ± SEM; p < 0.001), homocys-
teine and methionine did not. Both S-adenosylhomocys-
teine and 5-MTHF showed significant, but transient eleva-
tions after SAMe was administered (p < 0.001).
Whether SAMe supplementation might lead to eleva-
tions in homocysteine, promoting increased risk of coro-
nary disease, peripheral arterial occlusive disease, cere-
brovascular disease, or thrombosis is yet to be determined.
Certainly, further investigation using common chronic dos-
ing regimens of SAMe are warranted.
Interactions
Information documenting drug or food interactions with
SAMe is very limited. At least one case of serotonin syn-
drome has been described77 in a patient taking intramuscular
S-adenosylmethionine and clomipramine. It appears prudent
that patients avoid taking other antidepressants and possibly
other mood-altering agents while consuming SAMe, al-
though one small trial suggested SAMe shortened the time
to a therapeutic response when combined with imipramine.78
Additionally, until the significance of SAMe on MAO re-
ceptors is clarified, patients should avoid consuming foods
■ 2001 November, Volume 35 ■ 1421
CW Fetrow and JR Avila

containing high quantities of tyramine (aged foods, wines,
cheeses) and certain opium derivatives (meperidine, dex-
tromethorphan) because of the potential for this dangerous
interaction.
Dosage/Formulation
Consensus on appropriate dosing of SAMe is not avail-
able. Common doses employed in clinical trials have ranged
from 200 to 1600 mg/d. SAMe administration has been ini-
tiated in some clinical trials with intravenous formulations
and then switched to oral after a few doses or some period
of time after a documented response. Others have initiated
therapy with as little as 200 mg/d orally and titrated the dose
to a maximum of 1600 mg/d (divided in 2– 4 doses).
SAMe has been available for use in Europe for several
years and is sold as a dietary supplement in the US under
the Dietary Supplement Health Education Act. It is avail-
able most commonly as 200-mg tablets from various man-
ufacturers (e.g., Nature Made, Nutralife, Natrol, Jarrow,
Twinlab). One such example, produced by Nature Made,
retails (at time of writing) for approximately $17–20 for 20
(200-mg) tablets (daily doses of 1600 mg cost approxi-
mately $7–8 daily and $200–240 per month).79 However,
prices vary considerably between manufacturers. The re-
cent growth in manufacturer competition may ultimately
force SAMe prices to decline. Excipients in the Nature
Made tablet include 1,4 butanedisulfonate, cellulose, sodi-
um starch glycolate, methacrylic acid copolymers, talc,
polyethylene glycol, silica, magnesium stearate, polysor-
bate 80, sodium hydroxide, and iron oxide simethicone.
On occasion, SAMe is found to be available commercially
in combination with other supplements.
Patient Counseling
The popularity of this dietary supplement suggests that
pharmacists or other healthcare professionals will likely be
confronted with patients seeking advice relative to the con-
sumption of SAMe for various ailments. As healthcare
practitioners, it is important that we support the desire of
the patient to become empowered in the decision-making
process of their own health care. However, the provision of
a comprehensive educational approach combined with in-
dividualized consultation and specific answers to all ques-
tions is necessary for the patient before any reliable and in-
formed decisions can be made.
A reasonable counseling strategy for patients interested in
SAMe, as well as other dietary supplements, should include
discussions regarding (1) the relative lack of standardiza-
tion of SAMe as well as all dietary supplements (including
the paucity of information surrounding product absorption,
bioavailability, and stability); (2) the current body of evi-
dence (or lack thereof) surrounding efficacy of the product
(inclusive of questionable study design of some studies, an
overwhelming majority of foreign publications and inves-
tigations, and manufacturer-sponsored trials); (3) the con-
siderably small amount of information used to promote the
safety of SAMe and other dietary supplements (particular-
ly any available information concerning possible contraindi-
cations, warnings, adverse effects, drug interactions, or al-
lergic reactions derived from patient reports or extrapola-
tions from animal study data); (4) the relative lack of con-
sensus regarding specific dosing and monitoring parame-
ters of SAMe and other dietary supplements; (5) the exam-
ination of possible existing allopathic alternatives that may
be suitable for the patient; and (6) the relative cost consid-
erations of existing allopathic treatments compared with
alternative therapy (Table 3).
Patients should be made to realize that it is extremely
prudent that they enlist the assistance of their primary care
physician to provide routine monitoring of all possibly rel-
evant laboratory testing to ensure the safety of the alterna-
tive therapy. After having determined the patient’s reasons
for pursuing the alternative therapy, caregivers may find it

Table 3. Counseling Points Relative to SAMe

Counseling Points Specific Issues
Standardization no true standards exist; different formulations would be expected to vary; although some information available regarding
absorption, little information discusses product stability and shelf-life
Efficacy although much data suggest effectiveness in mild to moderate depression, this is limited by small trials; inclusion of non-
typical patient populations and also manufacturer-sponsored studies suggest some reason for potential bias; like most
antidepressants, clinical evidence suggests not all patients respond to SAMe therapy; therefore, expect some patients
(20–30%) to fail therapy; be especially wary of patients with symptoms or ideology suggestive of severe depression who
may not respond sufficiently to SAMe therapy to avoid potential risk of suicide; realize that comprehensive therapy for
depression involves more than medication (e.g., psychotherapy, counseling, support groups); patients should be guided
toward enrollment in programs that rigorously monitor for success of therapy and potential relapse
Safety safety information not routinely collected; trials primarily pursued efficacy; contraindications exist for patients already re-
ceiving antidepressants; patients at risk for elevations in serum homocysteine concentrations; bipolar disease disorder;
corticosteroid dependency; potential interactions (serotonin syndrome) with other psychiatric drugs and some narcotic
analgesics; MAO inhibitor–type precautions; limited information on adverse effects suggest significant GI symptoms, hy-
pomania, cognitive dysfunction, anaphylaxis
Dosing/monitoring wide range of dosing used in trials; varies with intended use; no consensus on dosing or standards for monitoring
Allopathic alternatives various agents available to treat depression and osteoarthritis; little reliable therapy for fibromyalgia
Cost typically $6–8/d; exceeds cost of most allopathic agents used for similar indications

GI = gastrointestinal; MAO = monoamine oxidase; SAMe = S-adenosyl-L-methionine.

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useful to identify one or more objective measurements that
can be used to track the patient’s progress. Reevaluation of
the need for continuation of alternative therapy can be pur-
sued after attainment of an adequate therapeutic trial, the
duration of which should be agreed on by both patient and
physician. This period of time will serve to convince both
patient and physician of the potential value (or lack there-
of) of a particular alternative therapy. Patients may be con-
siderably more amenable to a return to allopathic therapies
after having given the alternative agent a sufficient oppor-
tunity to prove itself.
Recommendations
Larger-scale, placebo-controlled trials and comparative
trials comparing SAMe with selective serotonin-reuptake
inhibitors or other newer generation antidepressants are
still needed before definitive conclusions can be drawn re-
garding SAMe’s place in the pharmacotherapy of depres-
sion. SAMe therapy of fibromyalgia, and perhaps osteo-
arthritis, deserves further consideration and investigation
because of some promising early clinical trial data; howev-
er, no definitive recommendations regarding these poten-
tial applications can be made at this time. Other potential
therapeutic applications are still preliminary.
Although many studies have documented adverse events,
some severe, related to SAMe supplementation, further
study, especially long-term evaluation, is needed in this
area. As with other antidepressants, the risk of a switch to
hypomania is still problematic with SAMe. Whether SAMe
is truly an antidepressant with fewer adverse effects than
contemporary antidepressants has yet to be determined. In-
formation surrounding drug interactions and contraindica-
tions is limited. Of concern is the theoretical risk of artifi-
cially elevating homocysteine concentrations by SAMe
supplementation in patients prone to hyperhomocysteine-
mia, a rare but established risk factor for cardiac disease
and thrombosis.
Another issue of concern is the general lack of standard-
ization of dosage forms of dietary supplements. SAMe
supplements will need to be constructed to standardized,
reliable, stable dosage forms that can be used for future in-
vestigations. Without standardization of dosage forms,
sub- or supratherapeutic concentrations may be achieved
in clinical trials, with great variability in results.
Although SAMe appears promising in the pharmacother-
apy of depression, enthusiasm for its immediate therapeu-
tic application should be tempered by the fact that the risk–
benefit profile is not nearly as well described as that of
newer generation antidepressants. Patients should be ad-
vised to reconsider ingestion of this essentially unregulated
dietary supplement until sufficient discussion with their
primary healthcare provider, with respect to the current
body of evidence surrounding SAMe, has taken place.
Summary
The decision to embrace a new pharmacotherapeutic
agent can only be made after a thorough understanding of
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S-Adenosyl-L-Methionine
both benefits and risks. When the likelihood that a patient
might experience an adverse outcome is similar to, or even
slightly exceeds, the probability that a positive benefit will
occur, the pharmacotherapeutic option becomes less vi-
able. At this point in time, an incomplete knowledge base
exists for SAMe. It therefore appears prudent that existing
pharmacotherapeutic alternatives with known risk–benefit
profiles be considered before pursuing this particular alter-
native treatment. When examined on a global scale, SAMe
is not without risk for some individuals, nor does there ex-
ist an absolute lack of contemporary pharmacologic thera-
pies available for the majority of diseases in which SAMe
is claimed to be useful. Any recommendation for use at
this time seems premature, especially in light of the fact
that there exists a general lack of consensus with regard to
dosing, monitoring, and standardization of SAMe products.
CW Fetrow PharmD, Clinical Specialist, Pharmacy Services, Uni-
versity of Pittsburgh Medical Center — Passavant Hospital, Pitts-
burgh, PA
Juan R Avila PharmD, Faculty, Department of Psychiatry Resi-
dency Program, St. Francis Medical Center; Medical Therapeutics
Liasion, Sanofi-Synthelabo, Pittsburgh
Reprints: CW Fetrow PharmD, Pharmacy Services, University of
Pittsburgh Medical Center — Passavant Hospital, 9100 Babcock
Blvd., Pittsburgh, PA 15237-5842, FAX 412/358-3798, E-mail
fetrowcw@ph.upmc.edu
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EXTRACTO
OBJETIVO: Revisar la evidencia clínica publicada sobre el suplemento
dietético SAMe (S-adenosil-L-metionina).
FUENTES: La mayoría de la información fue obtenida por una búsqueda
de MEDLINE (1996–febrero 2001) además de información de fuentes
secundarias y terciarias, de acuerdo a la disponibilidad.
SELECCIÓN DE ESTUDIOS Y EXTRACCIÓN DE DATOS: Todos los artículos
identificados fueron evaluados, y toda la información relevante fue
incluida en este repaso.
SÍNTESIS DE DATOS: La mayoría de la evidencia de estudios clínicos es
sobre el uso de SAMe en varios desórdenes depresivos, osteoartritis, y
fibromialgia. El tamaño de la muestra y las dosis usadas en estos
estudios varía considerablemente. Varios repasos y por lo menos dos
meta-análisis examinaron la evidencia de SAMe para terapia de
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S-Adenosyl-L-Methionine
depresión en estudios completados antes de 1994, y concluyeron que
SAMe era superior a placebo para el tratamiento de desórdenes
depresivos y aproximadamente tan efectivo como los antidepresivos
tricíclicos. Mucha de la información disponible es sobre reportes de
casos aislados. SAMe es aparentemente bien tolerado, y la mayoría de
los efectos secundarios son quejas de problemas gastrointestinales leves
a moderados. Sin embargo, este agente no está libre de riesgo de efectos
adversos psiquiátricos y cardiovasculares significativos. No hay
disponible información relacionada a interacciones de SAMe con
alimentos y otros medicamentos.
CONCLUSIONES: Se debe orientar a los consumidores a evitar el uso de
este suplemento dietético hasta que lo discuta con su médico primario.
Aunque existe un potencial de aplicaciones terapéuticas para SAMe, su
perfil de riesgos es incierto en estos momentos para poder hacer
recomendaciones de uso. Los profesionales de la salud y consumidores
deben ser cautelosos hasta que haya disponible más información sobre
este suplemento.
Sonia I Lugo
RÉSUMÉ
OBJECTIF: Etudier les données de preuve cliniques existantes publiées sur
le complément nutritionnel SAMe (S-adenosyl-L-methionine).
SOURCES DE DONNÉES: La majorité des informations a été obtenue à partir
de la littérature primaire publiée identifiée à l’aide d’une recherche
MEDLINE (1966–fevrier 2001). Des informations ont également été
obtenues à partir de sources secondaires et tertiaires disponibles.
SELECTION DES ÉTUDES ET EXTRACTION DES DONNÉES: Tous les articles
identifiés à partir des sources de données ont été évaluées et toutes les
informations pertinentes prises en compte dans cette revue.
SYNTHÈSE DES DONNÉES: La majorité de l’évidence clinique étudiée porte
sur l’utilisation de SAMe dans divers troubles dépressifs, l’ostéoarthrite,
et la fibromyalgie. Le nombre de sujets inclus dans ces essais et les
doses employées varient considérablement. Plusieurs revues et au moins
deux meta-analyses ont étudié le niveau de preuve établi par l’utilisation
de SAMe dans le traitement de la dépression pour les essais achevés
avant 1994, et ont conclu que SAMe était supérieur au placebo dans le
traitement de troubles dépressifs, et à peu près aussi efficace que les
antidépresseurs de référence. Beaucoup de ces informations apparaissent
sous la forme de rapports de cas isolés ou d’essais cliniques individuels.
SAMe apparaît bien toléré, la majorité des effets secondaires consistant
en des sensations gastro-intestinales légères à modérées. Cependant, il
apparaît que cette substance n’est pas dénuée de risques d’effets
indésirables psychiatriques et cardiovasculaires plus significatifs. Il n’y a
pas d’informations relatives aux interactions entre SAMe et
médicaments ou aliments.
CONCLUSIONS: Il conviendrait de conseiller aux consommateurs d’éviter
de prendre, sans surveillance, ce complément nutritionnel sans
discussion suffisante préalable avec leurs professionnels de santé. Bien
qu’il existe un potentiel important d’application thérapeutique pour
SAMe, son profil incertain de risques exclut de donner des
recommandations définitives à ce stade. Les professionnels de santé et
les consommateurs feraient bien de modérer leur enthousiasme pour ce
complément nutritionnel jusqu’à ce que l’on dispose de suffisamment
d’informations.
Michel Le Duff
■ 2001 November, Volume 35 ■ 1425