What is folic acid?
Folic acid is the synthetic, man-made form of the naturally occurring folate (also known as vitamin B9). Folic acid is found in fortified foods, and in dietary supplements.
Natural sources of folate
You can get folate from the food you normally eat, including leafy vegetables (such as spinach, broccoli, and lettuce), okra, asparagus, fruits (such as bananas, melons, and lemons) beans, yeast, mushrooms, meat (such as beef liver and kidney), orange juice, and tomato juice.
The amount of folate that will be available for absorption after its ingestion depends on many factors, such as the intestinal environment, genetics, lifestyle, the presence of diseases, and other conditions. Folic acid is actually more problematic for the body than the natural folate.
The role of folate in your health
When converted properly folate acts as coenzymes (molecules that help accelerate reactions in the cells). These coenzymes are involved in the synthesis of genetic material and methylation reactions (the addition of methyl groups to DNA molecules), thus regulating gene expression.
For this reason, folate deficiency may result in chronic diseases caused by abnormalities in the synthesis of DNA and proteins, and the dysregulation of gene expression.
Methylfolate (the most bioactive form of folate) also helps to break down high levels of homocysteine in the blood. Homocysteine is an amino acid associated with an increased occurrence of cardiovascular disease & immune system problems when high levels are found in the blood.
Low folate is linked to health problems such as anemia, neural tube defects in newborns, cognitive decline, increased risk of cancer, miscarriages, Autism, Cerebral Folate Deficiency, and mood disorders.
Recommended dietary intake of folate
The official recommended dietary intake of folate for adults is 400 mcg. Pregnant and lactating women require 600 mcg and 500 mcg, respectively. It’s worth noting these RDIs were established many, many years ago and studies have shown there may be many reasons why taking more for certain conditions might be beneficial.
Folate is found in a variety of foods, and it´s also added to industrialized food in the form of synthetic folic acid. Folate deficiency can be associated with a poor quality diet.
Other factors that increase the risk of folate deficiency are:
- Alcoholism: when you drink alcohol, the absorption of folate is impaired.
- Pregnancy: When a woman is pregnant, she needs more folate for the development of the fetus. During the development of the baby, methyl folate helps to form the neural tube (the fetal part that later develops into the brain and spinal cord). Supplementation with folate is very important because it can help to prevent some major birth defects of the baby’s brain and spine.
- Intestinal surgery or malabsorption: people with celiac disease, inflammatory bowel disease, Crohn’s, leaky gut, etc. don’t absorb nutrients normally. Surgeries involving the digestive organs may reduce the acidity in the stomach, thus interfering with folate metabolism.
- Genetics: some people can´t metabolize folate properly due to a genetic mutation in the gene MTHFR.
Folate and depression
Depression is a serious mood disorder that affects how you feel, think, and handle everyday activities, such as eating, sleeping, and working.
Depression is one of the most common mood disorders in the US, and it’s caused by a combination of factors, including physiological, genetic, and environmental influences.
In a review including 22 studies carried out with 455,781 participants from 8 countries, the relationship between depression and eating habits were investigated. The authors found that people who had a higher intake of folate in their diets had a lower risk of developing depression. Conversely, those who eat more processed food had a lower intake of folic acid, and a higher risk of depression (Ljungberg et al., 2020).
If your levels of folate are too low, you will have a higher risk of developing depression. You may also experience more serious symptoms that last longer (see review, Bender et al., 2017).
Considering that individuals with depression have lower serum levels of folate and dietary folate intake than individuals without depression AND that folate supplementation improved the efficacy of traditional antidepressant medications, clinicians may consider folate supplementation for patients with depression.
Particularly the active form L-Methylfolate has gotten a lot of attention lately due to its significant results in some double-blind, randomized studies.
The role of folate in depression
In your body, folate is metabolized into S-adenosylmethionine (SAMe), a compound involved in the synthesis of dopamine, norepinephrine, and serotonin, neurotransmitters which play a role in depression. Thus, if you have a folate deficiency, lower levels of these neurotransmitters are observed, providing a favorable neurochemical environment for depression.
Moreover, low levels of folate are also linked to higher levels of homocysteine, which is associated with depression severity as well as other health maladies like cardiovascular and immune system problems. It is believed that people who can´t metabolize folate properly (convert it into L-Methylfolate) because of a genetic mutation are more likely to develop depression.
If you´re depressed and have low levels of folate in your body, then you´re less likely to respond to anti-depressant medications, and more likely to relapse after the treatment.
Longer-term research may be needed to investigate the beneficial effects of folic acid in the treatment of depression. Some researchers believe that folate acts gradually and cumulatively to relieve or prevent depression. However, the right dosage is still uncertain. The most promising results have come from a study where George I. Papakostas et. all found that high doses of the bioactive form of folate, L-Methylfolate, significantly raised mood levels in those dealing with depression.
Folic acid and post-partum depression
Post-partum depression is a condition on which a woman may experience mood changes after giving birth. Symptoms include insomnia, loss of appetite, irritability, and difficulty taking care of the baby.
One research study showed that supplementation with folic acid for more than 6 months during pregnancy is associated with a decreased risk for developing postpartum depression (Jing et al., 2017).
Anxiety and folate
Anxiety is your body´s natural response to stress. It´s normal to feel anxious and preoccupied before an important test or event. However, when this feeling is too big that starts to interfere with your daily activities, it´s a sign that something isn´t right.
Anxious people often feel restless, worried, and have problems concentrating and sleeping. They may have heart palpitations, and dizziness as well.
Similar to depression, anxiety is caused by an imbalance between brain neurotransmitters involved in mood regulation, such as serotonin and noradrenaline.
To date, there are only a few studies that have investigated the effects of folate in anxiety disorders, and their results are inconsistent. While some of them point to an association, others couldn´t find it.
One study was carried out with a woman with a mutation in the MTFR gene, meaning that she had problems breaking down folate into its active form, L-Methylfolate needed for cellular absorption. After receiving treatment with folic acid, she reported having her anxiety alleviated. She also took vitamin B12 and other medications (Anderson et al., 2016). Most doctors agree that providing the direct active form to individuals who cannot break down folate or folic acid into L-Methylfolate is best for their health. It results in more normal coenzyme activity as well as restoring better health to the body and stops unmetabolized folic acid from building up.
It´s been shown that combined therapy with L-Methylfolate, cognitive therapy, and medication can be beneficial for people with depression and anxiety. In fact, studies have shown that folate supplementation adds to the pharmacological treatment, boosting the results of the medication.
In one study, 10 adolescents with treatment-resistant depression received an L-Methyl folate supplementation (the active form of folic acid). 80 % of them demonstrated improvement in depression, anxiety, and irritability, meaning that folic acid can be used as an adjunct to antidepressant treatment, and may be a safe and effective strategy for managing treatment-resistant depression in pediatric patients (Dartois et al., 2019).
Moreover, the right dosage and duration of the treatment to achieve the desired results are yet to be determined. More scientific studies are necessary to reach a conclusion regarding the benefits of folic acid supplementation in the treatment of anxiety.
Remember: it´s very important to take care of your mental health, seek medical help if you´re experiencing symptoms of depression or anxiety.
Talk to your doctor about L-Methylfolate. If you´re deficient, s/he may recommend a diet containing foods rich in folate, and suggest taking a dietary supplement containing the most bioactive form of folate for maximum cellular absorption.
Although folate is safe and well-tolerated by most individuals, do your research and check in with your healthcare provider to decide how much is right for you. If you choose to take a high dose of L-Methylfolate, but sure to take an active B12 supplement form like hydroxocobalamin, adenosylcobalamin or methylcobalamin along with it, otherwise folate alone may hide the effects of vitamin B12 deficiency.
Ebara, Shuhei. "Nutritional role of folate." Congenital anomalies 57.5 (2017): 138-141.
Ljungberg, Tina, Emma Bondza, and Connie Lethin. "Evidence of the Importance of Dietary Habits Regarding Depressive Symptoms and Depression." International Journal of Environmental Research and Public Health 17.5 (2020): 1616.
Bender, Ansley, Kelsey E. Hagan, and Neal Kingston. "The association of folate and depression: A meta-analysis." Journal of psychiatric research 95 (2017): 9-18.
Yan, Jing, et al. "Association between duration of folic acid supplementation during pregnancy and risk of postpartum depression." Nutrients 9.11 (2017): 1206.
Janet Trujillo, Matias Costa Vieira, Jaqueline Lepsch, Fernanda Rebelo, Lucilla Poston, Dharmintra Pasupathy and Gilberto Kac, A systematic review of the associations between maternal nutritional biomarkers and depression and/or anxiety during pregnancy and postpartum, Journal of Affective Disorders, https://doi.org/10.1016/j.jad.2018.02.004
Anderson, Shanna, et al. "Anxiety and Methylenetetrahydrofolate Reductase Mutation Treated With S-Adenosyl Methionine and Methylated B Vitamins." Integrative Medicine: A Clinician's Journal 15.2 (2016): 48.
Dartois, Lauren L., Danielle L. Stutzman, and MaryAnn Morrow. "L-methylfolate Augmentation to Antidepressants for Adolescents with Treatment-Resistant Depression: A Case Series." Journal of child and adolescent psychopharmacology 29.5 (2019): 386-391.
George I Papakostas, et al. “L-Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials. “ Am J Psychiatry 169:12, December 2012
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