L-methyl folate supplement and depression

This week's focus is on mental health.

I've recently started using genetic tests as part of the management of patients coming in for depression. One of the genetic tests included in the standard panel identifies a defect in the MTHFR gene. This gene is involved in the metabolism of L-methylfolate.

Why is L-methylfolate important? Because it is needed to make three neurotransmitters critical to  mood--serotonin, dopamine, and norepinephrine. (Neurotransmitters are chemicals that transmit information in your brain and other parts of your body.)  It indirectly regulates levels of these neurotransmitters, so if your L-methylfolate levels are low it could lead to a deficiency in neurotransmitters.

The MTHFR gene is involved in the conversion of the folic acid that we get from our diet or vitamins to the L-Methylfolate form that is the only form that can cross the blood brain barrier. What this means is that you can eat a lot of foods containing folic acid, take vitamins that include folic acid, and have regular levels of folic acid in your blood, but if you have this mutation you cannot convert it to the form that the brain can use. And if your brain is deficient in L-methylfolate, you may not have the building blocks necessary to make enough of these important mood regulating neurotransmitters. Furthermore, if you don't have the ingredients to make them, you can try antidepressant after antidepressant but still get a less than optimal response. Kind of like throwing more and more flour into a bowel in the hopes of  making bread but never adding  enough yeast. You can't get a loaf of bread without all the right ingredients.

MTHFR gene mutations are very common, reportedly as high as 50% in some ethnicities. The genetic testing company that I use reports that people with one mutation (ie heterozygous individuals) have about a 30% reduction in L-methylfolate, whereas people who are homozygous for the mutation have about a 70% reduction.

What I've noticed in people who carry the mutation is that they will often respond well for a short period of time after starting an antidepressant, but then their symptoms return. It is thought that this response is because they do have some of the "ingredients" to make what they need, so when an antidepressant is first started they do well for a bit, but they quickly use up the ingredients they have  and become depressed again. And adding on more antidepressants simply won't work.

For people who carry the mutation who are experiencing depression, L-methylfolate supplementation can be very helpful. (To view a study that supports this statement click here.) L-methylfolate is available over the counter (a lot of my patients buy it on Amazon) and by prescription (called Deplin). But remember, it is L-methyl folate, not just folic acid. Studies show the best response is at a dose of 15mg every day. Side effects are minimal, with gastrointestinal complaints being the most common (occurring in approx 10% of people).

Do you need the genetic test before considering supplementation? No. If  your depression has been resistant to treatment, you might give L-methylfolate a try with out any testing. However, always check with your physician before starting any medication (even natural ones).