How Folate (Vitamin B9) is Helping with Depression?


Vitamin B9, also known as folate, is essential for the formation of red blood cells and DNA, making it crucial for healthy cell growth and function. Additionally, folate is important during early pregnancy to reduce the risk of birth defects of the brain and spine. While some people use the terms folate and folic acid interchangeably, folic acid (pteroylmonoglutamic acid) refers to the synthetic form of vitamin B9.

Low levels of folate have been linked to depression, and in some cases, a poor response to antidepressants.


Folic Acid and the Brain

Folic acid, which is needed to make DNA and RNA, the building blocks of genes and an important component of cells, is also quite active in the brain and central nervous system. It affects the production of certain essential compounds and neurotransmitters—substances that carry messages to different parts of the brain.

For example, folic acid deficiency leads to lower levels of S-adenosylmethionine (SAMe) in the brain. Some research has suggested that supplementation with SAMe can play a positive role in the treatment of depression. One possible theory is that low folic acid levels leads to low SAMe, which increases symptoms of depression. By improving folic acid status, SAMe increases, and depressive symptoms drop.



Many studies, going back to the 1960s, show an elevated incidence of folate deficiency in patients with depression. 2 Studies vary depending on the criteria used to define folate deficiency, but often, about one-third of depression patients were deficient. Given that depression is often accompanied by decreased appetite and weight loss, the high incidence of folate deficiency in depression patients is not surprising. However, there is some evidence, though not conclusive, that folate deficiency may be involved in the etiology of depression in a minority of patients. Alternatively, depressed mood may decrease appetite, lower folate levels and thereby help to prevent recovery from depression. A recent review and metaanalysis looked at the results from the limited number of studies that investigated the effect of giving folate to depression patients and concluded that “there is some evidence that augmentation of antidepressant treatment with folate may improve patient outcome.”

In a 2003 U.S. population study of 2,948 people, ages 15 to 39, folate concentrations were significantly lower in people with major depression, compared to those who did not have depression. Plus, a 2020 study found that increased levels of folate and vitamin B12 play a major role in the link between a healthy diet and decreased depression rates.



Good sources of vitamin B9 include:

·         spinach and other dark leafy green vegetables

·         liver

·         asparagus

·         Brussels sprouts

·         black-eyed peas

·         nuts

·         eggs,

·         citrus fruits, and

·         fortified grains


Dosage and Side Effects

Taking high doses of folic acid supplements may cause side effects, including accelerating mental decline in older adults and increasing the likelihood of cancer recurring.

Because folic acid is more readily absorbed than folate from food, the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine have developed dietary folate equivalents (DFEs) to set clearer folate intake recommendations.

1 mcg DFEs equals:

·         1 mcg of folate from foods

·         0.6 mcg of folic acid from fortified foods or dietary supplements consumed with foods

·         0.5 mcg of folic acid from dietary supplements taken on an empty stomach

There is no upper limit (UL) established for naturally occurring folate from foods. However, the National Institutes of Health (NIH) recommends that adults over the age of 19 limit their intake of folic acid from fortified foods and supplements to 1,000 mcg per day. The UL for children is even less, ranging from 300–800 mcg depending on age.

Possible overdose side-effects:

1.       Can mask a vitamin B12 deficiency

2.       May accelerate age-related mental decline

3.       May slow brain development in children

4.       May increase the likelihood of cancer recurrence



Medications that can interfere with vitamin B9 include:

·         Anticonvulsants. Taking folic acid with fosphenytoin (Cerebyx), phenytoin (Dilantin, Phenytek) or primidone (Mysoline) might decrease the drug's concentration in your blood.

·         Barbiturates. Taking folic acid with a drug that acts as a central nervous system depressant (barbiturate) might decrease the drug's effectiveness.

·         Methotrexate (Trexall). Taking folic acid with this medication used to treat cancer and autoimmune diseases could interfere with its effectiveness.

·         Pyrimethamine (Daraprim). Taking folic acid with this antimalarial drug might reduce the effectiveness of the drug

·         Sulfasalazine (to treat ulcerative colitis)


Sources and Additional Information:



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