Has your mood been down, depressed? Maybe you're lacking energy and motivation. In this article we're going to look at methylfolate for depression, and specifically we're going to look at some of the research behind this — what it means for people with MTHFR, and for those without an MTHFR gene alteration.
Using folate and folic acid for the treatment of depression is not really a new concept, but the use of methylfolate is fairly new, or relatively new.
What's interesting to note is that some of the research on methylfolate for depression is in people that don't actually have MTHFR gene alterations.
For those of you not familiar with this concept: MTHFR is an enzyme that all of us have, but when it's altered it leads to alterations in how we metabolize folate, and it renders the person's enzyme less capable of making methylfolate.
Giving these people with the gene alteration more methylfolate does seem to help in a lot of ways, including fatigue, depression, and anxiety, among other things. People with an MTHFR alteration clearly do have a reduction in their ability to produce methylfolate.
Based on some of the research that I recently came across, it seems that even those without an MTHFR gene alteration but with depression may benefit from methylfolate. Well, why could this be?
There are other genetic alterations that some people may have, such as folate transport gene alterations. And then also, maybe they're just not consuming enough folate in general, including folic acid, in their foods. So there's an overall reduced delivery to the areas that are needed to help with neurotransmitter production. Perhaps these are some of the reasons.
Treatment-resistant depression is a common cohort of patients that different things are tried on. For one, they've already kind of maxed out all the things they could try. But for two, if it works on this population, there's a good chance it probably will work on other people with depression as well.
So in 2010 a study looked at this population, and they found that adding methylfolate to a standard therapy for depression such as an SSRI was effective at reducing depressive symptoms.
In another study, patients were recruited from 124 different primary care practices throughout the U.S. The patients were randomly assigned to receive either methylfolate or placebo for 12 weeks. The primary outcome the research study was looking at was a change in the Hamilton Depression Rating Scale — this is a common depression scale that's used to measure the severity of depression symptoms.
The study found that the change in the Hamilton score was significantly greater in the methylfolate group compared to the placebo group, meaning that the improvements were greater. It also found that the methylfolate group was more likely to achieve remission of their depression symptoms than the placebo group. Remission in this case was defined as a seven or less on the Hamilton Depression Rating Scale. About 48 percent of the methylfolate group achieved remission versus 32 percent in the placebo group.
Overall they concluded that methylfolate is effective at improving depression symptoms in a real-world setting, and that it was also well tolerated by the patients that took it.
There are some other studies that were funded by the maker of Deplin, and these had even more positive associations, as you can assume. Deplin is a prescription/over-the-counter product that has high doses of methylfolate in it, and so those studies of course may have a bit of a conflict of interest.
But still, it is interesting that there are findings suggesting methylfolate is effective at improving depression even in people that don't have MTHFR.
I don't typically give methylfolate to people without MTHFR or some sort of folate deficiency. And even those with an MTHFR gene alteration, I usually start slowly and carefully, because of the potential for side effects. In the right person at the right time it can be really, really helpful to uplift mood and stabilize some of the negative thought patterns.
If you're thinking about using this approach for your depression or mood issues, it's important to work with a healthcare provider that knows and understands this particular supplement/medication. Too much can actually have the opposite effect on your energy, mood, and well-being — which is exactly why methylfolate makes some people feel worse.
If depression has been resistant to everything else you've tried, it's also worth reading about the MTHFR connection to treatment-resistant depression.
If you want help working out whether methylfolate belongs in your plan — and at what dose — schedule an appointment and we can go through your genetics, labs, and symptoms together.