Researchers from the School of Pharmacy at Cedarville University in Ohio set out to determine the efficacy, safety and optimal dose of SAMe on central nervous system health, evaluating reported effects on measures of mood, behavior, anxiety and sleep.
“Mental health conditions are common, with a global burden of one in eight people affected according to the World Health Organization (WHO),” they wrote in the journal Nutrients. “Since the COVID-19 pandemic, the prevalence of depression and anxiety have risen approximately 28% and 26%, respectively.”
They also noted that The State of Mental Health in America 2024 report found that only 36% of youth with at least one major depressive episode said treatment helped “a lot” while 65% said it helped “some”, adding that many therapies may cause adverse effects such as weight gain, nausea/vomiting and sexual dysfunction.
SAMe for central nervous system health
SAMe—a natural compound produced in the liver from amino acid L-methionine and adenosine triphosphate (ATP)—is known for its role as a methyl donor in a variety of biological processes.
“Some of these include DNA and RNA gene expression and neurotransmitter secretion, including dopamine, norepinephrine and serotonin, which help elevate mood and support cognitive processes,” the researchers explained.
“The replenishment of depleted neurotransmitters in central nervous system signs, like major depressive disorder, is important; however, the beneficial effects of SAMe may also be due to its anti-inflammatory properties.”
While they noted that the effects of SAMe on depression and other mood disorders are not fully established, low levels of SAMe have been reported in patients with major depressive disorder.
According to data from market insights firm SPINS for the 52 weeks ending July 14, 2024, SAMe accounted for close $850,000 in dollar sales across U.S. multi outlet and natural retail channels in a calmative and mood support supplement category valued at over $386 million.
Efficacy and safety
The researchers conducted a systematic search of the PubMed, CINAHL and Web of Science databases to generate 36 acceptable studies of the 1,881 non-duplicate results generated.
These studies, conducted over a median period of eight weeks, included a total of 1,799 participants (60.1% female for those that specified gender) and SAMe dosing ranging from 200 mg to 3,200 mg (depending on the sign), with 800 mg being the most common dose. Assessments used to determine efficacy included various mood-related tests, EEG mapping and psychometry, MRI and plasma SAMe levels.
A total of 33 studies examined efficacy outcomes, while 29 studies included safety outcomes.
Overall, SAMe was effective in 24 of the selected studies, with adverse events mostly consisting of mild, transient gastrointestinal disturbances, the study reported. As study limitations and explanation for some of the variability observed, the researchers pointed to differing dosing strategies, SAMe formulations, patient populations, disease states, combinations and assessment tools.
“Current evidence suggests that use of SAMe improves depressive symptoms both as a monotherapy and with concurrent antidepressant or nutraceutical therapy,” they concluded. “Clinicians should consider individual patient factors (e.g., specific disease treated, SAMe formulation and dose, patient comorbidities, medication history, goals of therapy, etc.) that could support the use of SAMe.”
The review suggested that future studies assess SAMe’s long-term efficacy and safety in depression, further explore its effects alongside other therapies and ensure optimal dosing given inconsistencies in oral formulations.
Source: Nutrients
doi: https://doi.org/10.3390/nu16183148
“S-Adenosylmethionine (SAMe) for Central Nervous System Health: A Systematic Review”
Authors: Kyrie Eleyson R. Baden
