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 benefit for liver
injury
SAM-e protects liver cells from toxic injury, both experimentally-induced in
animals and in isolated liver cells. The mechanisms by which SAM-e protects
liver cells from injury result from the pathways of SAM-e metabolism. SAM-e
replacement can improve glutathione deficiency. SAM-e is a precursor to
glutathione production. For more
SAMe info
regarding the role of this supplement in alcohol induced liver injury.
SAM-e and depression
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.
Additional Potential SAM-e benefits
Cancer -- SAM-e may reduce liver toxicity in cancer patients undergoing
chemotherapy (Santin). SAM-e may help with
fibromyalgia symptoms.
SAM-e danger or side effects
with SAM-e supplements
There is some danger with SAM-e supplements in high dosages.
Q. I started taking Nature Made Sam-e complete.
This Nature Made SAM-e product has 400mg. The first two days had very bad head
aches then for 2 days I had stomach cramps. This is day 5 and I'm vomiting. i
just thought my body needed to get used to it. I'm not depressed or have
problems like some. I do not take any other medications. do you suggest a
smaller dose or just stop taking the product? i tried sam-e for my mood swings.
My mood is much calmer. can a person have such severe multiple reactions to a
product with natural ingredients.
A. SAM-e does have dangers when taken in high dosages. Many people
think that natural supplements can't possibly cause serious side effects, but
they can if misused. In our opinion, for long term use, SAM-e supplements work
better at a dosage of 50 to 100 mg.
Q. I take 400 mg of sam-e each day (one 200 mg tab
in AM, one in PM), and noticed that I get a really significant eye twitch that
lasts around 10 minutes about 1 hour after each dose. It seems obvious that the
sam-e is causing this eye twitch side effect, but have you heard of this eye
twitch side effect? Any idea what the mechanism might be that causes it?
A. It is possible that SAM-e is causing the eye twitch, and it may
be due to the influence of SAM-e supplements on certain neurotransmitters.
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.
Natrol
SAM-e,
200 mg
Jarrow
SAM-e,
200 mg
Source
SAM-e,
200 mg
SAM-e and
Arthritis
SAM-e helps support the incorporation of sulfate
groups into proteoglycans which help maintain cartilage and protect joints. Some studies have suggested that SAM-e possesses
anti-inflammatory and tissue-healing properties that may help protect the health of
joints, and perhaps may lessen pain. It is quite possible that SAM-e may be useful for
people with osteoarthritis, although more research needs
to be done in this area.
SAM-e caution and side effects
High doses can lead to anxiety and restlessness, and even insomnia. Long term side
effects are currently not known. The effects seem to be additive over several days of use,
hence dosage may need to be reduced with time. Some do well on even 50 or 100 mg (one
quarter or one half of a 200 mg pill) per day.
SAM-e may induce a manic swing in those with
bipolar disorder.
Q. I had ordered some sam-e a couple of weeks ago and
I have noticed sam-e side effects. This supplement makes my stomach hurt and I
have to take some sort of stomach med in order to take it. Is this normal? Also
does it come in lower dosage than 200mg?
A. It is best to take SAM-e supplements with breakfast, and one can
bite off half or a third of a 200 mg tablet and use the rest the next day. It is
possible that some people may notice a mild SAM-e side effect such as
gastrointestinal symptoms. Some companies do sell SAM-e 100 mg tablets.
SAM-e Summary
SAM-e is a useful therapeutic agent for depression and perhaps arthritis
and other disorders. Long-term studies are needed with SAM-e before making
widespread recommendations for its use. However, short-term human studies thus far have
found it to be effective.
Dr. Bottiglieri and colleagues, from Baylor
Research Institute, in Dallas, Texas, published a review article on SAM-e and other methyl
donors. They summarize, "SAM-e is required in numerous methylation reactions
involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The
synthesis of SAM-e is intimately linked with folate and vitamin B12 metabolism, and
deficiencies of both these vitamins have been found to reduce central nervous system SAM-e
concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and
psychiatric disturbances including depression, dementia, and peripheral neuropathy.
Studies support a current theory that impaired methylation may occur by different
mechanisms in several neurological and psychiatric disorders."
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 (p < 0.01). 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.
SAM-e improves depression in patients with Parkinson's disease
Researchers at Beth Israel Medical Center in New York report a study of S-adenosyl-methionine
(SAM-e) in 13 depressed patients with Parkinson's disease. SAM-e is an amino-like
nutrient naturally present in the body and available as a supplement in health
food stores. All patients had been previously treated with other antidepressant
agents and had no significant benefit or had intolerable side effects. SAM-e was
administered in doses of 800 mg per day for a period of 10 weeks. Eleven
patients completed the study, and 10 had at least a 50% improvement on the
Hamilton Depression Scale. One patient did not improve. Two patients prematurely
terminated participation in the study because of increased anxiety. One patient
experienced mild nausea, and another two patients developed mild diarrhea, which
resolved spontaneously. Although uncontrolled and preliminary, this study
suggests that SAM-e is well tolerated and may be an alternative to the
antidepressant agents currently used in patients with Parkinson's disease.
Comments: SAM-e is a available over the counter in a dose of 200 mg.
It is widely used in Europe to treat depression and has also been somewhat
helpful in treating alcoholic liver cirrhosis and osteoarthritis. We often start
my patients with 100 mg in the morning and build up to a maximum of 200 mg twice a day. High doses can lead to anxiety and restlessness. Prolonged use of
SAM-e should only be done under medical supervision.
Sam-e
Emails and comments
Q.
You
mentioned that Sam-e may cause anxiety in some. Does this mean that if you have anxiety
you should not take it? Will the anxiety subside once the body adjusts to the supplement?
A. Anxiety is dose dependent, 50 or 100 mg should not cause anxiety, and it is difficult
to predict in each individual how they will respond to SAM-e, whether anxiety will develop
or not.
Q. I've
been doing some research on SAM-e. What surprises me is the dosage you suggest. Other
websites, studies and merchants uniformly recommend that therapeutic levels for depression
are 800 to 1600 mg/day. I even found one site that said that dosages of 400mg to 800mg
SAM-e
recommended by some manufacturers are NOT usually therapeutic and not to get discouraged
if you don't notice results using label recommendations. Have you had patients who
only responded to higher doses?
A. It is possible that severely depressed patients may need up to 800 mg a day, however,
most patients with mild to moderate depression respond on 100 to 200 mg a day, and the
effects of SAM-e are enhanced over several days of use. If too much is taken side effects,
including insomnia, occur, which is counterproductive to mood enhancement. Many studies
are done short term and use high doses to elicit a response, but this does not mean that
high doses should be taken forever.
Q. Can Sam-e cause higher blood pressure
in individuals who had previously had a history of low blood pressure?
A. One small study did not indicate sam-e raised BP, however, it is possible that
some individuals who respond with higher bp after sam-e intake.
Q. It was suggested for me to take 25mg of Zoloft for a
week then increase to 50mg for mild depression. I preferred to take a natural
substance and I did some research on Sam_e and purchased 20 200mg of Sam-e. I took
two 200mg this morning now this afternoon I'm experiencing anxiety.
A. Anxiety is a very common side effect of SAM-e in doses
greater than 100 or 200 mg.
Q. Hello. Id like to know how much sam E to take
for mild to moderate depression. I’m also not sure where to buy this product as
some people are saying that there are a lot of fake products around. Thank you
for your great site!!
A. The dosage of SAM-e can range from 50 mg to 200 mg a day, and
each person is different on what they respond to initially and over time. The
dosage of SAM-e may be reduced over time since the effects accumulate and are
additive from previous days. You can find SAM-e sold at
Physician Formulas.
Q. Great information on your web page about Sam-e:
Since your information is so complete on Sam-e , I decided to give you some
input. I purchased on e-bay some expired Sam-e, from Pharmaton. It had an
expiration date from about 13 months. I read on the book Stop depression Now,
that Sam-e could last up to 3 years , if properly stored. Therefore I got a lot
of 8 30 pill 400 mg packages. Well they made me feel ill. I felt nauseated and
just plain ill with just one pill. I thought it was just me, and contacted 2
other people that bought from the same person other lots. They told me the same
thing, they felt ill when using it. I don’t know if it was bad SAM-e because it
was old, or perhaps because Pharmaton no longer makes it after just a year of
having it in the market and it wasn’t working. Do you have any idea of what
happened? The Sam-e Pharmaton used to make was the Italian type, the one that
contains the other preserver which is suppose to make the pills last longer !
Yes, Sam-e makes you anxious, very anxious, I had to use Inderal to help me with
the heart palpitations. Your low dosage suggestions make a lot of sense , and I
will follow them now that I have a recurring depression ,( or withdrawal from my
previous AD ).
A. It is possible that new 400 mg of SAM-e could give the nausea
just as easily, it is also possible that there were chemical alterations in the
SAM-e over time since it is an unstable molecule that does not store and stay as
well as other nutrients.
Q. Have you found Sam-e to cause weight gain?
Also, does the SAM-e dose have to keep being increased to get an effect from it?
A. We don't have any reason to believe SAM-e causes weight gain.
The SAM-e dose required for an effect actually is less over time.
Q. I stopped taking Prozac about a year ago. After
experiencing symptoms of depression along with anxiety and sleeplessness I have
started taking Sam-e with favorable results. So far I have not had an increase
in anxiety but because of the warnings on your website will possibly lower my
dosage if this occurs. Can I take a sleep aid containing GABA along with the
Sam-e? Do these contradict one another?
A. SAM-e may cause insomnia in high doses and it is preferable to
take less SAM-e than to have to counteract it with a sleep aid.
Q. I started taking sam-e (400 mg) about 2 months
ago for depression and knee pain and both greatly improved. I always took it
with food and always with a vitamin. 3 weeks ago I got the flu and stopped
taking it momentarily and now that I'm taking it again, this time on a empty
stomach, I have noticed it doesn't seem to be working as well. Is it possible to
better absorb it with food then without? The box says to take SAM-e on a empty
stomach, but before I always took it with my daily vitamin and I always take
that with food for it upsets my stomach to take it without. I'm only curious to
know why it says it best taken on an empty stomach. I know with some
supplements, taking them with with food can neutralize their potency. Does this
happen with sam-e? I don't seem to be having any side effects from taking it on
a empty stomach, but I'm very tired which is what sam-e helped with to begin
with and now doesn't seem to be helping with at all. Because the only side
affect I seem to know about is anxiety, which I know is not my issue, I'm
wondering if taking this high dose on a empty stomach could be causing fatigue
as a side affect.
A. The instructions on a bottle may not always be correct, and even
if they are most of the time, they may not apply to everyone. In your case SAM-e
is probably better absorbed with food. High doses can lead to fatigue, we don't
think long term use should exceed 100 or 200 mg a day. It may take trial and
error to find the ideal sam-e dosage and frequency of use, along with the ideal
time to take it which could be different from person to person.
Q. I was reading on your site about SAMe, and had some thoughts come up.
Years ago, I started taking SAMe in the midst of what was classified as severe
depression. I started at 400 mg like the box recommended, but ended up at 1200
most days and occasionally 1600 a day. During that time I was in a really sick
relationship and remember acting completely insane, being extremely reactive and
impulsive, thoughts racing beyond comprehension. I became self destructive and
my OCD was awful. I eventually got into recovery and started doing better mostly
(from the codependant relationship). Eventually the depression was still so bad
I switched to Wellbutrin- the med my mother has taken for almost 20 years. I
remember feeling weird for a while at first, but then better and with what I
thought were relatively few side effects. However, my "codependent" thoughts
still continued at times to run me out of my mind and behave in ways that felt
out of control. Sometimes Ive felt paralyzed and unable to move as my thoughts
have spiraled. I also experienced "buzzing" in my muscles to the point where it
was hard to sleep sometimes. I read recently that this might be known as "akathasia".
While I still know that I am a codependent and need to keep attending Al-Anon
meetings, I also am starting to wonder if the meds have effected me way more
than Ive known! I should also mention that I have become a serious workaholic
artist during this time, being pretty "successful" but feeling unable to stop
myself from working too hard on projects or at school...
A. Long term use of certain medications and supplements can cause
changes in the brain. Some people may benefit from taking breaks or switching to
other supplements or meds.
Q. I have been taking Sam-E instead of the
overpriced prescription anti-depressant that I used to take. Sam-E has worked
just as well if not better that the prescription anti-depressant. I would like
to try Passion Rx, but I read that Dr Sahelian doesn't advise taking it with
Sam-E. Is there a product that is safe to take Passion Rx with or on alternating
days? Can I take Mind Power Rx and Passion Rx?
A. SAM-e is very potent and should not be taken with herbal
products that have a stimulating nature. It is best to learn how each product
works by itself before combining.
Q. I read your site about sam-e, trying to find some help for my father's liver failure due to Hepatitis C, hoping to slow the progression and buy him some time, or maybe help him feel better for the time he has left. I want to let you know that Sam-e can be found in the veterinarian pharmaceutical industry under the brand of Denosyl from Nutramax Laboratories, Inc. My cat actually takes it in 90 mg dosages (it has done wonders for him, bringing his out of control enzyme tests down to normal levels in 3 months! [his damage is due to chronic steroid use]), and SAM-e is available in different dosages for dogs and cats (I am not sure what increments at this time), and it is enteric coated! I am actually checking into obtaining it if my dad's hepatologist approves it. My vet is selling me the cat's SAM-e for about $1 per pill, so no discount here.
Q. JI bought some SAM-e 200mg yesterday, and after
reading your info will now cut the tablets in half. 10 years ago I had anxiety
with panic attacks, and was given tricyclic antidepressants. Within 6 months I
had put on 40 pounds, and have only been able to lose a little bit of this
excess weight, even since stopping the meds 6 years ago. I hate being fat, and
if I wasn’t depressed when I started the meds I certainly was afterwards! My
question is – does SAM-e affect weight, as so many of the antidepressants seem
to?
A. No, SAM-e does not seem to induce weight gain or cause an
increase in appetite.
Q. I take Topomax for headaches and come to find
out, it helps my moods. I was wandering can I take Sam-e with my medications
because of my joint pains and help with my sluggish times.
A. SAM-e has side effects and needs to be used cautiously and in
small amounts. We can't advise whether you should or should not take a SAM-e
supplement with or without Topomax, that is the decision of your health care
provider who may wish to read this SAM-e page.
Q. Could Sam-E have anti viral effects and be used
with people who have hepatitis B as an alternative way of treatment?
A. We are not aware of SAM-e having any antiviral effects.
Q. Last year after the death of my father, a
family member recommended taking Sam -e to help with the natural blues I was
experiencing ( this was recommended to her by her doctor.) I did so with SAM-e
400 to 600 mgs a day and have felt that it helps me. I also recently started
taking melatonin and tryptophan tablets together at night to help with my
insomnia. I have the type of insomnia where I can go to sleep but then wake up
periodically all night long. I understand this is fairly common in "peri-menopause"
for women in their mid to late 40s and wanted to self treat. The tryptophan and
melatonin tablets seem to help although I am still not getting a full night
sleep the majority or even less than half the time. My questions are these: Is
it "bad" to be combining these? i.e. the Sam-e, tryptophan and melatonin? By
"bad" I mean, could use of all 3 give one too much serotonin or cause an
imbalance in other areas.
A. There is no simple answer. However, SAM-e does cause insomnia
and sometimes a lower dosage works better since deep sleep is essential to mood
balance. Tryptophan and melatonin are safe supplements as long as they are not
used every night.
Q. SAM-E was highly recommended by a couple of
people I know and trust, I'm considering trying it, maybe starting with SAM-e
100mg per day (half of a 200mg tablet). Would Sam E be contraindicated in one
with mitral valve prolapse? Since I have a combination of anxiety and depression
(not alternating but simultaneous) would SAM-E likely be OK at a low dose (your
material says that SAM-E has been known to actually cause anxiety in some)? Why
is there such a broad range of dosage recommendations (even for beginning) from
various professional websites; anything from starting with 100 mg per day to
starting with 400 or 800 per day?
A. We are not aware of studies with SAM-e used by people with
mitral valve prolapse so we are not sure how this supplement would affect this
condition. SAM-e does cause anxiety in some people, and it is usually dosage
related, the higher the SAM-e dosage, the more likely anxiety will set in. SAM-e
also has a tendency to build up in the system, therefore dosages may need to be
lowered over time. There is a wide range of opinions on natural supplements on
the internet. Some people who write about supplements may not have the necessary
medical knowledge or experience.
Q. I recently placed an order for my husband
for Passion Rx, he is going to try it for the first time. He is 44 years old and
in good health, the only thing is that he has been taking 1 pill of Sam-e 400mg
per day for 1 month. My question (if you can answer) is, can he continue to
drink the 400mg per day of Sam-e while taking the Passion Rx? and if so, should
he decrease the amount of mg per day? I understand that according to what I read
on your website, you really don't like to answer these type of questions, I am
only asking if you would please give me some kind of general answer. My
husbands' Doctor does not believe in herbal supplements which is why I see
myself in the position of asking for your assistance.
A. SAM-e is very potent, and so is Passion Rx. We
definitely do not recommend taking them together on the same day. In the long
run Passion Rx is only needed a couple of days a week.
Q. Is it safe to take Sam-e and Xanax or other
benzodiazapines when needed?
A. As a general rule involving the combination of supplements and
medications, first one has to become familiar with each supplement and
medication by itself, and then, under the guidance of a medical doctor who is
familiar with both, a small amount of each can be tried together before
proceeding to higher dosages. There is a great variety of individual responses
and therefore it is not possible to predict accurately the response of any one
individual.
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