Folate, also known as folic acid or Vitamin B9, is an important nutrient, present in leafy green vegetables and in fortified grain products. Low folate levels have been associated with depression and dementia in some studies-- those studies need to be updated to take account of the widespread use of fortified grain products (required in the U.S. since 1998) and B vitamin supplements (B6 and B12 in addition to B9).
Folate is easily inactivated by cooking and processing food, and folate levels may be affected by many other factors, including chronic disease, diabetes and other metabolic problems, cancer, smoking, alcohol use, poor diet, and medications such as mood stabilizers, L-dopa, statins, oral anti-diabetic drugs, and cancer chemotherapy. In addition, genetic variations in the MTHFR gene may reduce the ability to benefit fully from oral folate supplements, and may be related to folate deficiency. Thus, folate levels should be tested before more intrusive treatment is used for depression or mild cognitive impairment.
A 2009 review coauthored by Mischoulon showed methylfolate supplementation to be effective as an adjunctive therapy with psychotropic drugs or as a stand-alone treatment for both men and women in:
- reducing depressive symptoms in people with normal and low folate levels,
- improving cognitive function and reducing depressive symptoms in elderly people with folate deficiency, and
- reducing depressive and other symptoms in people with depression and alcoholism.
The risk is minimal.
Mental Health Implications
Folate is a promising stand-alone and adjunctive treatment for depression. Supplementation of folate deficiencies is recommended by five sources and only disavowed by one, the Natural Standard, and adjunctive treatment of depression with folate is a promising practice, especially for women, even if folate levels are not low. Although the Natural Standard concedes that folate has been used adjunctively, for enhancing treatment response to antidepressants, it does not credit the evidence in its rating. Two of the sources counsel supplementation even in the absence of folate deficiency, and while one leading researcher (Bottiglieri) does not explicitly concur with that recommendation, his description of the research would place him in the same camp. Another leading researcher (Mischoulon) does not view folate supplementation as effective in people with normal folate levels.
Researchers have observed some potential positive effects of folate and other B vitamins (B6 and B12 in addition to B9) on the aging brain, , but folate supplementation appears to be a promising practice only for mild cognitive impairment. Like ginkgo biloba (see that topic), it may not help prevent or treat dementia. Still, almost everyone should be sure to eat lots of leafy green vegetables (and fortified grains, if they are well tolerated)--especially as they get older and their appetites decrease and maladies multiply. And B vitamin supplements are a prudent neuroprotectant.
Side Effects & Drug Interactions
Aside from allergic reactions, folate and B vitamins are generally quite safe. However, the Natural Standard lists many medical conditions that may require folate supplementation and possible prescription drug interactions which should be considered by prescribing physicians. No interactions with psychotropic drugs have been noted. Folate is not toxic. There appears to be no reason for children or pregnant or lactating women to avoid folate.
Promising, but not yet proven.
- Folate is especially promising for depression if lithium or SSRIs are ineffective or poorly tolerated, and it is particularly promising for women.
- Folate is also promising for mild cognitive impairment.
- A diet rich in leafy green vegetables is good for almost everyone.
- B vitamin supplements are a prudent neuroprotectant.
For detailed information on Folate and other treatments, download the full review.