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SAM-e: More Like a Vitamin Than Medication

SAM-e is a nutritional supplement that has only been available in the United States for 20 years after it was discovered in Italy in 1952. Although it is only accessible by prescription in Europe to cure ailments including depression and arthritis, Sam-e is gaining popularity among Americans for various health issues.

SAM-e is manufactured in the body from methionine, an amino acid found in wild fish, eggs, sesame seeds, and oats. Our bodies use it to make certain chemicals and manage vital cell processes. Although SAM-e occurs naturally in our bodies, supplement manufacturers create a copy of the molecule for sale.

What Is SAM-e (S-adenosylmethionine)?

SAM-e, also known as s-adenosylmethionine, is created in the brain from methionine, an essential amino acid that helps grow new blood vessels, and adenosine triphosphate (ATP), a source of energy within our cells. It is produced naturally by the body and has been found to affect essential functions in living cells.

S-adenosylmethionine is a crucial participant in the human methylation process, which helps maintain several biochemical processes in the body and is involved with gene expression, DNA repair, cell membrane fluidity, protein, etc., neurotransmitter synthesis, and fat and mineral metabolism.

SAM-e has been linked to many benefits, including improved mood and anxiety relief. According to one review published in the Journal of Psychiatry & Neuroscience, it is involved in over 35 methylation reactions. (1)

SAM-e has numerous metabolic functions throughout the body, and it participates in the synthesis, activation, and disintegration of a variety of molecules, including proteins and hormones.

It raises serotonin turnover and possibly dopamine norepinephrine levels. It's been shown to have analgesic and anti-inflammatory effects while simultaneously enhancing physical function, and it's frequently used to reduce pain while increasing bodily function. (2)

SAM-e is a naturally occurring chemical present in almost all body tissues and fluids. It is involved in a variety of vital activities. For example, it impacts the immune system, cellular membranes and the production and degradation of brain chemicals such as serotonin, melatonin, and dopamine.

It works in tandem with vitamins B9 and B12. So, if you are getting enough folate and vitamin B12, this may diminish SAM-e levels in the body.

SAM-e has been used to treat pain associated with osteoarthritis in several studies. SAM-e has also been studied as a treatment for depression. Researchers have also investigated the use of SAM-e in fibromyalgia and liver disease, and the results were inconclusive.

Many of the initial studies utilized SAM-e intravenously or as an injection. Researchers have recently examined the effects of SAMe taken by mouth. (3)

SAM-e Potential Benefits

Effective as an Antidepressant

S-adenosylmethionine has been shown in several placebo-controlled studies to have antidepressant effects, but the evidence is still uncertain. However, SAM-e levels are typically lower in depressed people than those who don't show symptoms of depression. Therefore it's thought that when used for depression, it may have beneficial effects.

SAM-e has been found to affect several aspects of the pathophysiology of major depressive disorder, according to a comprehensive analysis published in CNS & Neurological Disorders Drug Targets in 2016. In addition, according to several randomized controlled trials, S-adenosylmethionine is superior to placebo and tricyclic antidepressants.

According to the research, SAM-e has shown promise in nonresponsive serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor patients. (4)

According to a 2008 study by researchers in Melbourne, Australia, SAM-e therapy was superior to the placebo among males but not females when treating major depressive disorder. This double-blind, randomized controlled trial suggests that gender may impact the antidepressant effectiveness of SAM-e; male patients experienced more significant therapeutic benefits. (5)

SAM-e has been more effective than a placebo in treating mild-to-moderate depression and just as effective as antidepressants without the adverse side effects (sleeplessness, headaches, and sexual difficulties). Antidepressants also take 6 to 8 weeks to work, but SAMe begins working faster.

SAM-e's exact mechanism of action in lowering sadness is still not fully understood. However, it may work similarly to some antidepressant medications by increasing the amount of serotonin in the brain.

SAM-e May Improve Brain Function

SAM-e is an important molecule that aids in the process of methylation, which supports a variety of biological processes, including the brain. The loss of methyltransferase function, linked to age-related neurodegenerative diseases such as Alzheimer's, is common.

Levels of SAM-e appear to be lower in people with Alzheimer's disease, potentially affecting their metabolism and brain activity. (6)

S-adenosylmethionine also stimulates the action of enzymes involved in the synthesis of glutathione, a potent antioxidant that works within cells. According to studies, decreased glutathione levels might be linked to Alzheimer's and other neurodegenerative diseases. (7)

It's still debatable whether or not S-adenosylmethionine supplements can help with cognitive decline in humans, but some promising animal studies are to consider.

Researchers looked at the effects of SAM-e on cognitive function in mice as determined by maze performance in a study published in PLoS ONE. Maze performance is a mouse's spatial learning and memory test. Researchers found that supplementing with SAM-e improved cognitive performance, especially among folate-deficient mice, based on 13 studies. They discovered that S-adenosylmethionine might enhance spatial memory in people suffering from many dementia types, including Alzheimer's disease. (8)

Mental Health Implications of SAMe

SAM-e appears to be a beneficial therapy for depression, according to five of seven sources. SAM-e can be taken alone or in combination with other antidepressants. Because its adverse effects are less than antidepressants, SAM-e is more easily tolerated by many individuals: It works faster and has no weight gain, sexual dysfunction, drowsiness, or cognitive interference.

SAM-e has been shown in studies to be beneficial for treating mild, moderate, and even severe depression (Brown et al.). It's also been dubbed a "first-line CAM therapy" for mild, moderate, or severe sadness by one prominent researcher (Brown et al.).

Supports Liver Function

SAM-e synthesis is believed to be depressed in individuals with chronic liver disease, and this deficiency may worsen the condition. As a result, it is thought that SAM-e supplementation might be beneficial in treating liver conditions.

SAM-e is thought to be beneficial and safe for treating chronic liver diseases, according to researchers. S-adenosylmethionine appears to help improve liver function. Therefore, it may be used as part of a therapy plan for liver health; nevertheless, according to several studies, it does not improve outcomes or decrease the rate of adverse events in individuals with chronic liver disease.

Overall, further research is required on the primary therapy of liver disease using SAM-e before definitive recommendations can be made. (9)

Sam-e Works as Natural Pain Reliever

SAM-e supplements are famous for their pain-relieving qualities, which is why they're commonly used to treat lower back discomfort, joint problems, PMS symptoms, and abdominal suffering.

Although S-adenosylmethionine has been shown to help with several ailments, research on its pain-relieving abilities is still in its early stages. Some promising research exists. A pilot study in 2013 conducted at the University of California found that children who took oral SAM-e had minor stomach discomfort.

A 1,400-milligrams-per-day course was given to 14 children with functional abdominal pain for two months. SAM-e improved self-pain reports over the treatment period, according to researchers. (10)

Advantages of SAM-e Compared to Prescription Antidepressants

Antidepressants currently available have a delayed onset of action, so mood improvement may not be evident until four to six weeks of daily usage. SAMe, on the other hand, has a rapid onset of action and generally takes only one week to start working.

SAMe has a favorable safety profile, with few side effects and no clinically significant drug interactions when used appropriately. Few side effects are in stark contrast to antidepressants, which frequently have numerous negative interactions.

There is evidence that SAM-e (400mg) twice a day in people not responding to antidepressant therapy improved memory and other cognitive deficits that often accompany sad moods. (11)

Available Forms of SAM-e

SAM-e is available as tablets or capsules, which are more stable and reliable regarding the amount of SAM-e in the pill. They should be kept cool and dry but not refrigerated. Tablets should be kept in a blister package until you're ready to use them.

SAM-e, a precursor to the major neurotransmitters in the brain, and a mix of precursors to the key nervous system chemicals are included in an excellent supplement,Vital Mind.

Possible Drug Interactions

If taking any of the following drugs, you should not take SAM-e without first consulting your doctor.

The risk of getting serotonin syndrome may be higher when SAM-e is taken at the same time as these medicines:

Antidepressant medications

SAM-e may cause adverse effects when combined with antidepressant medications, such as headache, accelerated or irregular heart rate, anxiety, and restlessness.

Many people report experiencing a reduction in depression after using SAM-e. However, many antidepressants, too, boost serotonin levels in the brain. As a result, concerns have emerged over whether combining the two might cause serotonin to get out of control. If you're taking pills for depression or anxiety, please consult with your doctor before taking SAM-e.

Levodopa (L-dopa)

The efficacy of this medication for Parkinson's disease may be reduced by SAMe.

Medications for diabetes

The use of SAMe may cause blood sugar to fall and has the potential to enhance the efficacy of diabetes medications, putting you at a higher risk for hypoglycemia.

Risks and Side Effects

The adverse effects of SAM-e are generally uncommon. They are frequently minor complaints such as stomach upset or nausea when they occur. Still, SAM-e has been known to cause adverse side effects, including sleeplessness, anxiety, and nervousness.

S-adenosylmethionine might aggravate manic symptoms. Therefore, it's recommended that individuals with bipolar disorder avoid taking the supplement unless it's under the care of their health care provider.

SAM-e may react with various medicines and nutritional supplements, particularly those that raise serotonin levels, such as L-tryptophan, St. John's wort, and antidepressant medications.

There's also worry that SAM-e encourages the growth of Pneumocystis carinii, a potentially deadly fungal infection that affects immunocompromised persons, such as those with HIV. Although further study is needed on this topic, persons with a compromised immune system should not take S-adenosylmethionine unless advised by their doctor.

There is still a lot to learn about whether SAM-e is safe to take during pregnancy or while breastfeeding. Studies on children taking SAM-e have been done, and there was no observable toxicity in the children who took it. However, it would be best to start your child on SAM-e or any other supplement only after consulting with their pediatrician.


SAM-e, more like a vitamin than medication, is a natural metabolite that the body requires more of as we grow older and sick. SAM-e is generally safe and supported by evidence for the treatment of depression. It's also being studied as a potential neuroprotectant and ADHD therapy. If it weren't for the cost and lack of insurance coverage, it would be preferred to most prescription antidepressants because of their efficacy.

Looking for a quality SAM-e supplement?

Our Vital Mind supplement contains SAM-e and is designed for those looking for a brain supplement that will help them to increase all aspects of their mental performance while maintaining a calm, balanced mood and without any negative effects on sleep.

Our Vital Mind supplement is also part of our Brain Protocol and Brain Protocol+ bundles, which add our Neuro Calm and Magnesium Supplements, which, alongside Vital Mind, act as the yin and yang, are designed to harmonize the rise and fall of alertness, focus, and calm states throughout the day by providing all of the building blocks needed for neuronal signaling.