From the Guidelines
5-MTHF is not proven to be effective for treating depression. The provided evidence does not directly support the use of 5-MTHF for treating depression, as it primarily discusses the effects of folate on vascular function and cardiovascular risk 1.
Key Points
- The study suggests that high-dose folate treatment may have beneficial effects on myocardium, but this is not directly related to depression treatment 1.
- There is no mention of 5-MTHF being used as a treatment for depression in the provided evidence.
- The example answer suggests that 5-MTHF may be used as an adjunctive treatment for depression, with dosing ranges from 7.5 to 15 mg per day, but this is not supported by the provided evidence.
- In real-life clinical practice, caution should be exercised when considering 5-MTHF as a treatment for depression, as the evidence is not strong, and traditional antidepressants should be considered as the primary treatment option.
- More research is needed to fully understand the potential benefits and risks of using 5-MTHF for depression treatment.
From the FDA Drug Label
A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed, although not established in controlled trials, that treating such an episode with an antidepressant alone may increase the likelihood of a precipitation of mixed/manic episode in patients at risk for bipolar disorder. Denovo is not an antidepressant However, 5-MTHF has been shown to enhance antidepressant effects of known antidepressants. L-METHYLFOLATE CALCIUM Tablets is not an antidepressant; however, 5-MTHF has been shown to enhance antidepressant effects of known antidepressants.
The FDA drug label does not directly state that 5-MTHF is effective for treating depression, but it does mention that 5-MTHF has been shown to enhance antidepressant effects of known antidepressants 2 3.
From the Research
Efficacy of 5-MTHF in Treating Depression
- The effectiveness of 5-methylfolate (5-MTHF) in treating depression has been explored in various studies 4, 5, 6, 7, 8.
- Research suggests that 5-MTHF, also known as L-methylfolate, may enhance the synthesis of monoamines, suppress inflammation, and promote neural health, leading to improved outcomes in patients with depression 4, 5.
- Studies have found that 5-MTHF may be particularly beneficial for patients with selective serotonin reuptake inhibitor (SSRI)-resistant depression, as well as those with biomarkers of inflammation or metabolic disorders 4, 8.
Mechanism of Action
- 5-MTHF is involved in the re-methylation of homocysteine, creating methionine, which is then converted to S-adenosylmethionine (SAMe) 6.
- SAMe is involved in numerous biochemical methyl donation reactions, including the formation of monoamine neurotransmitters, such as serotonin, norepinephrine, and dopamine 6.
- 5-MTHF may also stabilize, enhance production of, or possibly act as a substitute for tetrahydrobiopterin (BH4), an essential cofactor in monoamine neurotransmitter biosynthesis 6.
Clinical Evidence
- A systematic review and meta-analysis found that adjunctive L-methylfolate improved antidepressant response in adults with major depressive disorder (MDD) 7.
- Another study found that L-methylfolate increased clinical response when used adjunctively in patients with MDD who were SSRI-resistant 8.
- Post-hoc analyses suggested that patients with inflammation and/or obesity responded better to adjunctive L-methylfolate therapy compared to the overall sample 8.
Safety and Tolerability
- Folate, including 5-MTHF, is generally well-tolerated, and 5-MTHF may be less likely to incur certain risks associated with folic acid, such as increasing cancer risk or masking B12 deficiency 5.