Vitamin B9, also known as folate, is a B vitamin that has an important role in the formation of red blood cells. B9 also plays a role in the metabolism of protein, growth and division of cells, and prevention of neural tube defects. Apart from anemia and other health problems, folate deficiency can also lead to major depressive disorder (MDD). Folate deficiency or an inability to properly absorb folic acid, is linked to a poor response to antidepressant medications.
Sources of folate and barriers to absorption
Folate can be found naturally in fruits, vegetables, grains, beans, and a range of other foods, but in most people this natural form of folate is absorbed more easily than synthetic folate, because the body needs to convert folic acid back into folate before it can be used properly in cellular functions. While folic acid is added to lots of different processed foods, such as energy bars, cereals, and bread, you can still end up with a deficiency if your body is not able to absorb folate properly. In such cases, even if you are getting the recommended daily amount of folic acid (400 mcg), you can still end up with a deficiency.
Certain gastro-intestinal disorders like celiac disease, liver disease, genetic mutations (such as MTHFR), excessive alcohol consumption and alcoholism, pregnancy, and being on kidney dialysis can cause folate deficiency. Eating disorders and frequent vomiting during pregnancy can also lead to a deficiency. The amount of folate present in the blood may not be an accurate indication of the folate level in the central nervous system. When someone suffers from folate deficiency or has a medical condition that prevents the proper absorption of folic acid, the more bioavailable form—l-methylfolate—is recommended. The recommended dose is most often higher than the normal daily value of 400 mcg.
L-methylfolate for treatment-resistant depression
In the 1960s researchers first began to notice an association between folate deficiency and depression. While it is natural to feel a little “down” at some point, around 6-7% of adults suffer from major depressive disorder each year. Twice as many women are affected as men. Around 50-70% of people taking antidepressants don’t have a remission of their depressive episode.
Clinical trials and case studies suggest that these patients can benefit from l-methylfolate, which can improve their response to an antidepressant. While atypical antipsychotic medications are sometimes used to improve the effect of antidepressants, there are side-effects associated with these drugs including weight gain and dyslipidemia (which potentially increases triglyceride and LDL cholesterol levels). Some researchers advocate l-methylfolate supplements for people who do not respond very well to antidepressants. These supplements do not have major side effects as compared to antipsychotic medications. The human body generally tolerates l-methylfolate very well and it is available over-the-counter at reasonable prices.
How does it work
What makes l-methylfolate work is that it is the only form of folate that is able to cross the blood-brain barrier. It also has an important part to play in the synthesis of neurotransmitters. L-methylfolate is indirectly involved in the synthesis of dopamine, serotonin, and norepinephrine. These three neurotransmitters regulate your mood and have other important functions. L-methylfolate has been the subject of a range of studies which have shown that it can increase the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), two of the most commonly used antidepressants.
A folate deficiency or an inability to absorb folate due to certain medications, illness, or other genetic differences can enhance the risk of developing depression, better known as major depressive disorder. Treating the condition can be a challenge when a person has a folate deficiency. Supplementing with l-methylfolate can help people with major depressive disorder and those who aren’t responding well to their antidepressant medication. If you have a medical condition or are taking medications associated with poor folate absorption then you should consult your physician and find out if l-methylfolate would be good for you.