Biochemical properties of SAM-e
Unlike other methyl donors where the research is scarce, there have been a
number of studies with SAM-e. These studies have shown that SAM-e influences brain
chemicals by helping to convert norepinephrine to epinephrine and
serotonin to
melatonin.
Sam-e is also involved in the production of
creatine, which in
turn is phosphorylated to phosphocreatine using adenosine triphosphate.
Creatine is an important energy reservoir in muscle tissue
Sam-e helps the
preservation of glutathione, an important antioxidant.
Furthermore, SAM-e is involved in
the formation of myelin, the white sheath that surrounds nerve cells and it can improve
brain cell membrane fluidity, thus potentially enhancing the function of receptors.
SAM-e and Mood
Because of its role in the making of neurotransmitters, SAM-e has been tested in
the therapy of depression. A number of studies have been published, mostly in Europe,
evaluating this nutrient’s role in mood disorders. Back in 1994, Dr. Bressa, from the
University Cattolica Sacro Cuore School of Medicine, in Rome, Italy conducted a
meta-analysis of the studies on SAM-e. A meta-analysis is a statistical pooling of already
published research papers. Dr. Bressa concludes, "The efficacy of SAM-e in treating
depressive syndromes and disorders is superior to that of placebo and comparable to that
of standard tricyclic antidepressants. Since SAM-e is a naturally occurring compound with
relatively few side-effects, it is a potentially important treatment for depression."
The influence of SAM-e on depression has also been tested in the United States.
Back in 1994, researchers at the University of California, Irvine Medical Center, did a
double-blind randomized trial involving a total of twenty-six patients. They compared oral
SAM-e with oral desipramine (a pharmaceutical antidepressant). At the end of the four-week
trial, 62 percent of the patients treated with SAM-e and 50 percent of the patients
treated with desipramine had significantly improved. Similar results were found
in a 2002 study when SAM-e was compared to imipramine (Pancheri).
SAM-e has even been tested in depressed postmenopausal women. Researchers from
the University of La Sapienza in Rome, Italy gave SAM-e for thirty days to eighty women
between the ages of 45 and 59 with depression following either natural
menopause or
hysterectomy. There was a significantly greater improvement in depressive symptoms in the
group treated with SAM-e compared to the placebo group. Side effects were mild and
transient.
SAM-e has been found to improve mood in those with Parkinson's disease.
SAM-e
Availability
A major drawback to the use of SAM-e is cost. The retail price of SAM-e is
a little less than a dollar per 200 mg pill. The suggested dose of SAM-e in the therapy of depression
ranges from 100 to 400 mg a day, although many individuals do well with even
less than 100 mg. Since the lowest dose over the counter is 200 mg, one could
bite off half or a portion of a tablet and wrap it with plastic wrap for use the
next day.
Many nutrients work in a similar fashion to SAM-e,
particularly other methyl donors such as DMAE, TMG, DMG.
In fact, B12 and folate help the body produce SAM-e. Therefore, your dosage of SAM-e
should be reduced if you are taking other methyl donors. However, none of the
nutrients mentioned above work as well or as quickly as SAM-e in lifting mood.
SAM-e side effects
Q. I took 200 mg of SAM-e for depression every day and within 4 days it lifted
my mood. But on the fifth day I started getting SAM-e
side effects, feeling jittery, anxious and couldn't
sleep well. It seemed to negate the benefits I had the first few days.
A. These are typical SAM-e side effects. It is quite likely that the
initial 200 mg was fine for the first few days, but then the required dosage to
lift your mood dropped. But, by exposing yourself to the same initial dosage of
200 mg, it was too much for you. Many people find 100 mg every other day to be
good maintenance amount. But there is a wide range of response and each person
through trail and error has to find their ideal dosage and how to adjust it on a
daily basis.
Many drug and supplement side effects occur since doctors and consumers do not
realize the importance of constant dosage adjustment. Most doctors will put a
patient on a standard mg of a drug and do not consider reevaluating the
appropriateness of this initial dosage in subsequent weeks, months or even
years. Many doctors fail to grasp the importance of the uniqueness of each
individual and treat in a robotic manner using the same dosage of a drug for all
patients. Furthermore, the dosage required of a natural supplement or a drug can
vary over time depending on how the condition changes and many other variables
including diet, sleep patterns, physical activity level, season, temperature,
etc.
SAM-e Research Update
S-Adenosyl methionine (SAM-e) versus celecoxib for the
treatment of osteoarthritis symptoms: A double-blind cross-over trial.
Najm WI, Reinsch S, Hoehler F et al. BMC Musculoskelet Disord. 2004 Feb 26
SAM-e is a dietary supplement used in the
management of osteoarthritis (OA) symptoms. Studies evaluating SAM-e in the
management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs)
for comparison. The present study compares the effectiveness of SAM-e to a
cyclooxygenase-2 (COX-2) inhibitor (celecoxib) for pain control, functional
improvement and to decrease side effects in people with osteoarthritis of the
knee. A randomized double-blind cross-over study, comparing SAM-e (1200
mg) with celecoxib (Celebrex 200 mg) for 16 weeks to reduce pain associated with
OA of the knee. Sixty-one adults diagnosed with OA of the knee were enrolled and
56 completed the study. Subjects were tested for pain, functional health, mood
status, isometric joint function tests, and side effects. On the first
month of Phase 1, celecoxib showed significantly more reduction in pain than
SAM-e. By the second month of Phase 1, there was no significant
difference between both groups. The duration of treatment and the interaction of
duration with type of treatment were statistically significant. On most functional health measures both groups showed a notable
improvement from baseline, however no significant difference between SAM-e and celecoxib was observed. Isometric joint function tests appeared to be steadily
improving over the entire study period regardless of treatment.
SAM-e has a slower onset of action but is as effective as celecoxib in the
management of symptoms of knee osteoarthritis. Longer studies are needed to
evaluate the long-term effectiveness of SAM-e and the optimal dose to be used.
S-adenosylmethionine (SAM-e) supplementation for treatment of
chemotherapy-induced liver injury.
Santini D. aboratory of Internal Medicine and Hepatology,
Campus Bio-Medico University, Rome, Italy.
Anticancer Res. 2003 Nov-Dec;23(6D):5173-9.
Liver toxicity can be observed during treatment with most chemotherapic agents, and represents one of the principal causes of dose
reduction or chemotherapy delays. S-Adenosylmethionine (SAM-e) plays a critical
role in the synthesis of polyamines and provides cysteine for the production of
glutathione (GSH), the major endogenous hepatoprotective agent. Our study was
aimed at assessing the protective effect of SAM-e supplementation in cancer
chemotherapy-induced liver toxicity. Fifty cancer patients
who developed, for the first time, anticancer chemotherapy-induced liver
toxicity were studied. Enrolled patients received oral SAM-e supplementation.
AST, ALT and LDH levels recorded at the moment of the recognition of
liver toxicity were significantly reduced after one week of SAM-e therapy . AST,
ALT and LDH decrease was confirmed after two weeks of treatment. Furthermore,
the effect on these enzyme levels persisted in the following chemotherapy
courses, permitting our patients to perform the scheduled chemotherapy courses
with a minimal number of dose reductions or administration delays. The efficacy
of SAM-e supplementation was not influenced by the presence of liver metastases,
and no appreciable side-effects were recognized. The results of our
study clearly demonstrate a protective effect of SAM-e in cancer
chemotherapy-induced liver toxicity. Further large phase III studies are
required to assess the real clinical benefit associated with SAM-e
supplementation.
A double-blind, randomized parallel-group, efficacy and safety
study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAM-e)
versus imipramine in patients with major depressive disorder.
Pancheri P, Scapicchio P, Chiaie RD.
III Clinica Psichiatrica, Universita 'La Sapienza', Viale dell'Universita 30
(00185), Rome, Italy.
Int J Neuropsychopharmacol. 2002 Dec;5(4):287-94.
S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the
most important methyl donor in transmethylation reactions in the central nervous
system. Several clinical trials have shown that SAM-e possesses an
antidepressant activity. This multicentre study was carried out to confirm both
efficacy and safety of SAM-e in the treatment of major depression. SAMe was
given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d
oral Imipramine (IMI) in patients with a diagnosis of major depressive episode,
with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of
>or=18. A total of 146 patients received SAMe whereas 147 received IMI for a
period of 4 wk. The two main efficacy measures were endpoint HAMD score and
percentage of responders to Clinical Global Impression (CGI) at week 4.
Secondary efficacy measures were the final Montgomery-Asberg Depression Rating
Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of
at least 50% with respect to baseline. The analysis of safety and tolerability
was conducted in all treated patients. SAM-e and IMI did not differ
significantly on any efficacy measure, either main or secondary. Adverse events
were significantly less in patients treated with SAM-e compared to those treated
with IMI. These data show 400 mg/d i.m. SAM-e to be comparable to 150 mg/d oral
IMI in terms of antidepressive efficacy, but significantly better tolerated.
These findings suggest interesting perspectives for the use of SAM-e in
depression.
SAM-e questions
Q. I have been taking SAM-e for only four days, 200mg in the morning. It helped
rather quickly with mood and energy. On the night of the third day, however,
which was yesterday, I became pretty seriously ill. I felt as though I was going
to throw up several times during the night, and would sweat a lot as though with
fever when this happened. Before this happened, I had also became uncommonly
tired when the sun went down in the evening, which is not usual for me. This
happened again this evening, even though i cut my dose to about 75mg, and I
think I feel the upset stomach coming back. All day today my stomach was
unsettled and I was very fatigued, which is the opposite of what the SAM-e did
for the first two days. So I don't know whether this is from a virus or whether
it could be from the SAM-e. My general questions are: whether sickness from
SAM-e usually occurs, if it does occur, shortly after having taken the
medication, or whether nighttime nausea may also occur. Second, may unusual
fatigue in the evening, following stimulation, be a side effect? Another factor
is that I take pseudoephedrine as an alternative to amphetamine for attention
issues during the day. This does not, however, lead to any anxiety with the
SAM-e, as I realize it might, but could it be the cause of sickness? I am a 26
year old healthy male who exercises every day.
A. Yes, it is possible that nausea and fatigue could be due to too
much SAM-e. This nutrient is very potent and smaller amounts work better. Taking
SAM-e with pseudoephedrine or another stimulant can make the side effects worse.
Q. I recently had a bad anxious reaction to even the
lowest possible dose of 5 HTP so i washed it out for 4 weeks and am now trying,
SAM-e at just 1/2 of a 200 mg pill every other day for my depression and anxiety
combined with regular walks, fruit, fresh water, Hypnotherapy for relaxation etc
(Trying to avoid heavy SSRIs as they are bad for me and many others with side
effects). I experienced some mild short anxiety even at this dose of SAMe that
seems to pass ok, will this 100mg SAMe dose every other day be ok for me and
help with my symptoms in time? any idea how long it takes to build up? i don't
really want to try and increase to 400mg a day and risk further anxiety but do i
need to do that to kick my depression? OR will the 100mg accumulate gently in
time and work just as well? (i like the fact that it addresses all the neurotransmitters
and forms Myelin and is an antioxidant).
A. SAM-e does accumulate over days of use, and hence it is best to
use the lowest dose that works.
Q. I have been taking 200mg a day of L-Theanine for
quite a while and have found it very effective. Now fighting depression I'm
thinking of trying SAM-e. Is it a safe mix to take 100mg SAM-e in the morning
and 200mg in the evening? I would rather not give up the L-Theanine because of
how well it has worked but would you recommend higher doses of Vitamin B
instead, if so what dose?
A. We can't make specific individual recommendations. We suggest
reading the information on the SAM-e page for the benefits and side effects.
Different people respond differently to individual supplements and combinations.
One option is to begin using very low dosages.
Q. When I read your information about Sam-E, I became
curious about how it affects dopamine in the brain. I have an extra pyramidal
side-effect to Compazine and like anti-nausea drugs and the reason is due to how
they affect dopamine in the brain. Can you explain for me how Sam-E works?
A. SAM-e works by the process of methylation, it can transfer a
methyl group to other substances in the body and thus help increase levels of
several brain chemicals including dopamine. The full process is very complicated
and we are not biochemists so we don't know. We focus on the clinical aspects of
treatment.
Q. I took SAM-e 400mg a day for 2 years and have had acute anxiety attacks. Since I didn't have any side effects for the two years, I still didn't attribute the anxiety attack to the SAM-e and thought I was developing generalized anxiety disorder. After several small attacks over the months, I had a huge panic attack 10 months after the first one. I finally figured from reading your info on SAM-e that it might be the culprit. I stopped and have been getting better ever since. My symptoms were dizziness and vertigo, tingling numbness in extremities followed by panic, racing heart and high blood pressure, lasting three or more hours. The first attack I was extremely nauseas. Thank you.
Q. Although I haven't yet tried using SAM-e, I am
wondering if taking theanine or another anxiolytic supplement may help control
anxiety for those taking SAM-e, or if you have any other knowledge of their
interactions. It appears the two supplements affect different pathways, at least
directly.
A. We prefer using a lesser dosage of a supplement rather than
taking another one to counteract the side effects of the first supplement.
However, adding theanine in the evening is an interesting option and worth a try
if your doctor approves.
Q. I just wanted to let you know my experience after
taking SAM-E for a few days. I started taking SAM-E 3 days ago for mild
depression and I hoped it would give me a slight energy boost. Over this short
time period I have noticed a couple of effects, I get a tingling effect
throughout my body, especially at night and in the mornings, it feels good, like
I have more energy but I have no desire to actually get up and do anything. Last
night I just sat still resting on a pillow for maybe two hours in the early
evening, I didn't fall asleep but my mind just drifted off. Now this wasn't
unpleasant but it's something I don't normally do, I normally need to have some
external stimulation or I feel bored and restless. I'm also having the same
experience at night, I go to bed feeling quite restful but then just drift
without actually falling asleep for hours, last night I went to bed at 11PM
(normal for me during the week) and was awake in this state at about 2AM which
is very unusual for me, I've never really had any trouble sleeping. I find it
hard describing it as insomnia although I'm sure that's what it is because I
don't feel frustrated that I can't sleep, I feel calm at the time and quite
comfortable just lying there but my brain doesn't feel tired enough to allow me
to fall asleep. I am concerned that if this continues it could start to affect
my life during the day. I've been taking 200mg of SAM-E early in the morning and
was contemplating taking 200mg every other morning instead, do you think it's
better to cut the pill and take a small amount each day rather than miss days
out? I'm willing to experiment with this because I feel SAM-E has the potential
to help me through what is quite a difficult and stressful period of my life.
A. We prefer using smaller amounts of SAM-e in order to reduce the
side effect of insomnia. Some people may only need 100 mg every other day, or
even less. Since a higher dosage of SAM-e can cause insomnia, and lack of sleep
leads to low mood and energy, taking a high amount of SAM-e can be
counterproductive.
Q. Recently I read your article about long term use of
Sam-e and side affects. I have been using Sam-e for a very long time, like 7
years! I started using it for Menopausal symptoms. I have been kind of depressed
lately so I decided to do same research on Sam-e, that is when I discover your
site. Could you please tell me how I can wean myself. I take 2 first thing in
the morning, every morning, last few months I have been taking few times a week
one before lunch also. It was working fine until I am down more often then
ever!!
A. We suggest your doctor read this SAM-e page and advise you since
we are not in a position to make individual recommendations.
Q. I would like to know if it is ok to crush my SAM e
tablet. i cannot swallow pills. Does crushing/ biting the SAM e tablet
destroy its effectiveness?
A. No. It is okay to crush the SAM e tablet before swallowing it.
Q. I have been taking SAM-e tablets for approximately
three weeks and have had no urges to gamble or drink. I am a recovering
compulsive gambler and alcoholic and have had recent bouts with depression. My
counselor thought that giving SAM-e tablets a try would help, as she found it to
help other gamblers and alcoholics such as myself. It is a blessing for me, as I
can focus more clearly on rational thinking day to day instead of the delusional
thoughts that compulsive gambling had led me to believe. I will not admit that I
am cured but the relief I am experiencing has been amazing to say the least!
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