SAM-e supplementation can reduce symptoms of depression either by itself or as an adjunct treatment to antidepressant medications.
SAM-e is a compound that naturally occurs throughout your body.
It is central to the production of several major brain chemicals critical to mood, cognition, and healthy brain aging.
SAM-e is available as a supplement that is most often taken as a natural remedy for depression, and sometimes to ward off cognitive decline.
How SAM-e Works in the Brain to Help Depression
S-Adenosyl methionine (SAM-e) is an amino acid metabolite that is not found in food directly.
It’s produced in the body from ATP (the energy currency of cells) and methionine, an amino acid found in protein-rich foods. (1)
SAM-e is naturally present in every cell in the body and plays a role in a variety of functions. (2)
It is critical for the synthesis of several major neurotransmitters, chemical messengers that communicate between neurons in the brain. (3)
Depression is often the result of an imbalance in neurotransmitters such as serotonin, dopamine, or norepinephrine.
Serotonin is involved in sleep, learning, appetite, and mood. (4)
Dopamine is the “motivation molecule” that’s also in charge of your pleasure-reward system.
Norepinephrine influences blood pressure, heart rate, and the fight-or-flight response. (5)
These three neurotransmitters belong to a class of molecules called monoamines.
SAM-e, vitamin B12, and folic acid (B9) must be present for these critical monoamines to be synthesized in the brain. (6)
Prescription Antidepressants vs. SAM-e for Depression
According to the Centers for Disease Control and Prevention’s (CDC) data, 11% of Americans over the age of 12 took prescription antidepressants between 2005 and 2008. (7)
During this period, 254 million prescriptions were written.
Several studies indicate that the difference in the effectiveness between placebos and antidepressants is minimal.
Prescription antidepressants have only a 20% better efficacy than placebos in human trials. (8)
Doctors commonly prescribe selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac) or sertraline (Zoloft) as the first line of treatment because they are more effective and have fewer side effects than other antidepressant options. (9)
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SSRIs treat depression by addressing serotonin deficiency.
They do so by increasing the amount of time that serotonin stays in the synaptic gap between neurons.
SSRIs slow the reuptake of serotonin so that it can continue triggering feelings of well-being longer.
They can take 6-8 weeks before they begin to make a noticeable impact on a patient’s health.
Side effects of SSRIs including nausea, insomnia, dizziness, sexual dysfunction, blurred vision, drowsiness, diarrhea, restlessness, nervousness, dry mouth, and drowsiness. (10)
Taking pharmaceutical antidepressants can come with an increased risk of suicide.
Missing doses or cutting back on SSRIs can result in withdrawal-like symptoms and should be carefully monitored by a medical professional. (11)
And finally, patients often have to try several types of antidepressants before finding one, or a combination, that works.
Now let’s see how this compares to using SAM-e for depression.
The Benefits of SAM-e for Depression
Some studies indicate that taking SAM-e for depression is just as effective as taking an antidepressant.
SAM-e has been found to be so beneficial for depression that, in Europe, doctors have been writing prescriptions for it for decades. (12)
SAM-e is much faster-acting than most antidepressants, which can take six to eight weeks to become effective.
Many patients report a significant decrease in depressive symptoms after one week of SAM-e supplementation. (13)
Although it is known to cause mild side effects like headaches and insomnia, they are not as severe as those caused by prescription antidepressants. (14)
And unlike antidepressants which have many side effects, SAM-e offers some additional benefits including the treatment of osteoarthritis, fibromyalgia, liver disorders, and improving overall brain function. (15)
In short, SAM-e benefits are that it acts faster with fewer side effects than pharmaceutical antidepressants.
What the Research Shows About SAM-e for Depression
Researchers have used high-tech imaging to map the effects that SAM-e produces in the brain.
They’ve found that SAM-e activates the brain in ways similar to the effects of standard antidepressants.
In a study involving 20 healthy adult volunteers, participants received infusions of either 800 mg of SAM-e or a placebo for a period of seven days.
The participants’ brains were then scanned using electroencephalograms (EEGs) and low-resolution brain electromagnetic tomography (LORETA).
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The images indicated SAM-e to be an effective antidepressant.
It activated the same regions of the brain critical to the efficacy of tricyclic antidepressants. (16)
In a double-blind placebo-controlled study, ten elderly patients were injected with 800 mg of SAM-e and then evaluated for depressive symptoms as well as overall cognitive performance.
When their brains were scanned with EEG imaging, they displayed changes typical of those who take the antidepressants amitriptyline and imipramine. (17)
SAM-e seems to be well-tolerated by elderly subjects.
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According to data provided by PubMed Health, only one in five individuals treated with a prescription antidepressant will experience a reduction in symptoms when compared to a placebo. (18)
Patients who have become resistant to traditional antidepressants may benefit from augmented SAM-e supplementation.
SAM-e appears to be especially effective when combined with SSRIs. (19)
A 2004 study conducted by Harvard Medical School treated adult outpatients diagnosed with major depressive disorder with 800-1,600 mg of SAM-e during a six-week trial.
Participants continued with their normal regimen of either SSRIs or venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), throughout the study. (20)
NOTE: Never combine SAM-e with antidepressant medications without first speaking to your doctor.
Impressively, 43% of participants experienced a remission of depressive symptoms.
In 2010, the National Institute of Mental Health funded a follow-up study to investigate SAM-e as a treatment for patients who had become resistant to medically prescribed antidepressants.
Participants continued taking SSRIs throughout the study, but added 800 mg of SAM-e twice daily.
Within a 6-week period, patients who received the SAM-e supplementation displayed double the response rate and double the remission rate of depressive symptoms when compared to a placebo. (21)
Promising Uses for SAM-e: Dementia and Alzheimer’s
Besides depression, there is another promising use for SAM-e.
Preliminary research suggests that SAM-e may help slow or reduce the symptoms of degenerative brain diseases like Alzheimer’s.
Gene expression of amyloid proteins in the brain is closely linked to Alzheimer’s.
Researchers think that SAM-e reduces symptoms of dementia by regulating amyloid protein gene expression.
These amyloid plaques can accumulate in the brain and are a hallmark of Alzheimer’s disease.
In one study, elderly participants given SAM-e displayed a marked increase in total brainpower reminiscent of nootropic drug effects. (22)
Recent findings suggest that SAM-e supplementation has a direct effect on elevating glutathione levels in the brain and liver.
Glutathione is a critical antioxidant that protects the brain from damaging free radicals that contribute to brain disease.
The following 2009 study was led by the Department of Geriatrics Center for Aging Brains, University of Bari, Italy. (23)
According to the study, “the findings underscored the critical role of SAM in the maintenance of neuronal health, suggesting a possible role of SAM as a neuroprotective dietary supplement for AD patients.”
In a 2011 study, researchers induced dementia in mice by causing a B-vitamin deficiency.
Researchers found that SAM-e reduced the progression of Alzheimer-like symptoms.
Mice treated with SAM-e displayed reduced amyloid protein production and improved spatial memory. (24)
SAM-e Dosage, Side Effects, and Interactions
There is no recommended daily allowance (RDA) for SAM-e, but there are some general guidelines you can follow.
Doses of 200 to 1,600 mg/day have typically been used in depression trials, but doses of up to 3,000 mg/day have been administered. (25)
According to WebMD.com, up to 1,600 mg of SAMe can be taken daily, either alone or along with antidepressant medications. (26)
Separate this into two doses, one in the morning and one in the evening.
Because SAM-e supplementation can cause nausea, it’s best to start taking it in small doses of no more than 200 mg and take with food. (27)
Clinicians advise taking SAM-e with vitamin B12, methionine, folic acid, and trimethylglycine to improve absorption.
Low levels of folate and vitamin B12 have been linked to low levels of SAM-e and increased symptoms of both depression and cognitive decline.
SAM-e Supplement Side Effects and Interactions
SAM-e is generally considered safe. (28)
Side effects are uncommon and, when they do occur, are usually minor. (29)
Reported side effects include nausea, headache, dry mouth, diarrhea, restlessness, dizziness, anxiety, gas, sweating, feelings of elation, and heart palpitations.
Supplement during the day to optimize benefits.
SAM-e can make it hard to sleep if you take it too close to bedtime.
Feelings of elation can turn into mania (excessively elevated mood) when SAM-e is taken in large doses.
People with bipolar disorder shouldn’t take SAM-e for depression because it can exacerbate manic episodes and feelings of anxiety. (30)
There’s no real evidence that SAM-e helps anxiety, despite this being suggested by several sources across the internet.
Research on SAM-e for anxiety is minimal, and plenty of natural anxiety remedies are available without a prescription.
As I mentioned above, never combine SAM-e with antidepressant medications without first speaking to your doctor.
When taken together, they can cause serotonin syndrome, a dangerous condition caused by high levels of serotonin.
The following can lead to serotonin syndrome when combined with SAM-e: antipsychotics, amphetamines, narcotics, dextromethorphan (night-time cough syrup), and even St. John’s wort, another popular herbal remedy for depression. (31)
You should not take SAM-e if you’re pregnant or breastfeeding. (32)
SAM-e should never be given to a child unless under doctor supervision.
Benefits of SAM-e for Depression: The Bottom Line
SAM-e is a naturally occurring substance in the body and also a popular supplement for depression.
It can effectively reduce symptoms of depression both as a stand-alone remedy and as an adjunct treatment to antidepressant medications.
Compared to antidepressants, SAM-e works faster and with fewer side effects.
Additionally, SAM-e may slow cognitive decline by boosting glutathione levels and regulating gene expression of amyloid proteins in dementia and Alzheimer’s patients.
About the author
Justin Faraday is a former EMT and massive health and nutrition enthusiast. After struggling with his health for several years, he got serious about feeling incredible. Get stellar mental health and nutrition advice at his blog Dope.Fresh.Fit.