Folate: A Secret Weapon Against Depression?
Folate is the naturally occurring form of vitamin B9 found in foods such as asparagus, eggs, and leafy greens. People with depression tend to have lower blood folate levels than those who are not depressed. Early research shows that adding folate to antidepressants may improve the odds of a positive response to antidepressants.
Folate and Depression
Folate is connected to depression in at least two ways.
First, folate regulates the levels of tetrahydrobiopterin, or BH4, in the body. BH4 is an important cofactor in the formation of dopamine and serotonin, meaning that it must be present in order for them to be made. Disruptions in the levels of these two important neurotransmitters are associated with depression.
Folate deficiency → lower levels of BH4 → lower levels of serotonin & dopamine
Folate is also involved in the breakdown of homocysteine, a metabolic byproduct. Higher levels of homocysteine have been linked to many disorders including heart disease, Alzheimer's and depression.
Folate may be useful in the treatment of depression in individuals with elevated homocysteine and with mutations in the MTHFR gene, such as a homozygous 677 TT mutation.
Lower levels of folate are associated with a poor response to antidepressants while higher levels are associated with better response rates.
Folate is a potential new treatment for depression. A 2013 study that followed 554 patients, 502 of whom were treated with l-methylfolate plus their existing antidepressant and 52 were treated with l-methylfolate alone. In this study participants had a mean reduction of 58% on their PHQ-9 depression symptom rating. Sixty-eight percent of the participants responded to treatment (a 50% reduction in PHQ-9 scores) and 46% achieved remission (PHQ-9 score <5) after an average of 95 days of therapy.
Patients in this study also reported a significant reduction in self-reported impairment in their work, home, and social life. Patients in this study were generally more satisfied with l-methylfolate treatment than their prior medication.
Final Recommendations
Most people can get all the folate they require through a balanced diet alone. Whole foods like spinach, broccoli, beets, and lentils are excellent sources.
Folate supplementation may make sense for those who have mutations in the MTHFR gene and thus have a higher biological need for folate to keep their methylation cycle running properly. Testing for both MTHFR gene mutations and folate levels is available through both mainstream and specialty labs.
Dr. Lewis determines the need for folate supplementation by checking for MTHFR gene mutations, measuring blood folate levels and homocysteine levels. Based on the results of these tests and the overall clinical picture, we can then determine if folate supplementation alone or in addition to antidepressants is likely to be beneficial.
When supplementing, it is important to use the active form of folate, L-Methylfolate (or 5-MTHF) and not folic-acid, which could actually block the methylation cycle and cause more harm than good.
Dr. Lewis recommends starting with a lower dose of folate supplements and gradually increasing the dose. The dose of l-methylfolate is best adjusted based on the clinical response and blood homocysteine levels. Dr. Lewis does not recommend high-dose folate supplements in her clinical practice as too much folate may increase the risk for cancer and cardiovascular disease.
Impact of Depression on Quality of Life
Patient response to “How difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?” Note that “… these problems …” refers to the symptoms assessed on the 9-item Patient Health Questionnaire, which immediately preceded this question on the surveys.
Source: (Shelton, 2013)
Citrus fruits like oranges, lemons, grapefruits, and limes are puckeringly good sources of folate.