Most women know how important folic acid is to sustain a healthy pregnancy. But did you know that synthetic folic acid and folate are not the same thing? The metabolically active form of folate (known as 5-MTHF) has been found particularly effective for treating depression.
It is recommended that all women of childbearing age take folic acid supplements as pregnancy is not always a planned event. Low dietary intake of folic acid before and during pregnancy increases the risk for delivery of a child with a neural tube defect (NTD) such as spina bifida and anencephaly. Taking folic acid supplements before and during the early stages of pregnancy significantly reduces the occurrences of NTDs and results in increased infant birth weight and improved Apgar scores, along with a decreased incidence of fetal growth retardation and maternal infections.
What is folic acid? And how does it differ to folate?
Folic acid and folate are not the same. Folate is a natural form of vitamin B9 that is found in food sources. Folic acid is a water-soluble B vitamin created in a lab to add to supplements and foods. Folic acid needs to be broken down into folate (5-MTHF) before the body can use it.
Folate cannot be synthesised by our bodies. This means that we need to ensure that our diets are rich in folates. These folates must first be converted to the metabolically active form of folate 5-MTHF (5-Methyltetrahydrofolate) to be effectively utilised by the body. Although folates may be abundant in our diets, cooking or processing destroys them. The best folate sources in foods are green, leafy vegetables, sprouts, fruits and brewer’s yeast. Liver and kidney also contain high amounts of folates.
Folate deficiency is one of the most common nutritional deficiencies and may be caused by:
- Deficient food supply
- Defects in utilisation, as in alcoholics or individuals with liver disease
- Mal absorption
- Increased needs in pregnant women, nursing mothers, and cancer patients
- Metabolic interference by drugs
- Folate loss in haemodialysis
- Deficiencies in enzymes or co-factors needed for the generation of active folate
- Absorption of folic acid appears to be significantly impaired in HIV disease, irrespective of the stage of the disease
Signs and symptoms of folate deficiency include:
- Macrocytic Anaemia
- Fatigue
- Irritability
- Peripheral neuropathy
- Tendon hyper-reflexivity
- Restless leg syndrome
- Diarrhoea
- Weight loss
- Insomnia
- Depression
- Dementia
- Cognitive disturbances
- Psychiatric disorders
Improve your mood
The metabolically active form of Folate (as 5-MTHF) is involved in the formation of neurotransmitters – dopamine, norepinephrine and serotonin – and for this reason several exciting studies have looked at the potential role of folate (particularly 5-MTHF) in depression. Research shows depressed individuals have a high incidence of low folate levels or are folate deficient. These individuals also tend to not respond as well to anti-depressant drugs.
The metabolically active form of Folate (as 5-MTHF) has a high bioavailability (7 x higher than synthetic folic acid). Folate is stored in Red Blood Cells (RBC’s) and folate levels remain elevated for periods more than 40 days following discontinuation of supplementation. Folic acid has a low bioavailability and is poorly transported to the brain. Unmetabolized folic acid is rapidly cleared from the central nervous system primarily through the liver and excreted in urine.
Research has shown a link between folate deficiency and depression. Folate, specifically the form 5-MTHF has been used as stand-alone depression treatment or as an adjunctive treatment with anti-depressants. There are many causes of folate deficiency. Certain medications (such as anti-convulsants, antibiotics, oral contraceptives, and some anti-cancer agents) can deplete folate levels. Poor folic acid absorption, chronic diseases, alcoholism and poor diet are also causes of folate deficiency.
Genetics also play a key role in folate deficiency Folic Acid cannot be used by the body immediately, the body needs to break it down in a complex enzymatic process. Many individuals have MTHFR (Methylene Tetrahydrofolate Reductase – an enzyme present in the liver which is needed for the breakdown of Folic Acid into Folate) Polymorphisms. These individuals are unable to break down folic acid into 5-MTHF (Folate), which is the useable form of folate found in blood. Thereby making them folate deficient.
Taking Folate for your mental health
The advantage of supplementing with the metabolically active from of folate (as 5-MTHF), is that the body can use this folate form immediately. Folate plays a key role in the Methylation Cycle and the Methylation Cycle plays a vital role in the formation of neurotransmitters which in turn impacts mental health. Folate has been shown to work synergistically with anti-depressant therapy and may even help the treatment of depression when used simultaneously.
The treatment of depression is a complex issue. Its use and benefits should be discussed with your prescribing doctor, Folate supplementation has the potential to benefit depressed individuals who have folate deficiency!
This is different to supplementing with high amounts of folic acid. Too much folic acid can conceal a vitamin B12 deficiency.
Make a note to consult with your doctor or healthcare professional today before making any changes to your diet, medications or supplements.
References
- Cavalli P. (2008). Prevention of Neural Tube Defects and proper folate periconceptional supplementation. Journal of prenatal medicine, 2(4), 40–41.
- Scaglione F, and Panzavolta G. (2014) Folate, folic acid and 5-methyltetrahydrofolate are not the same thing, Xenobiotica, 44:5, 480-488, DOI: 10.3109/00498254.2013.845705.
- Prinz-Langenol R et al (2009). [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with homozygous or wild-type 677C→T Polymorphism of Methylene Tetrahydrofolate Reductase. British Journal of Pharmacology, 158: 2014-2021.
- Meshkin B and Blum K (2007). Folate Nutrigenetics: A convergence of Dietary Folate Metabolism, Folic Acid Supplementation and Folate Anatgonist Pharmacogenetics. Drug Metabolism Letters, 1: 55-60.
Willems F et al (2004). Pharmacokinetic study of the utilisation of 5-MTHF and Folic Acid in patients with Coronary Artery Disease. British Journal of Pharmacology, 141: 825-830.