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Methylfolate: A Natural Alternative to Antidepressants for Pregnant Women

Methylfolate: A Natural Alternative to Antidepressants for Pregnant Women 

Methylfolate: A Natural Alternative to Antidepressants for Pregnant Women

What Does it Mean to be the “Best” Methylfolate

Pregnancy is an exciting time in any woman’s life - but it can come with many challenges. The hormones that help to physically prepare the woman’s body for the growing fetus also have an impact on her mental health. For some women, this hormonal flux can lead to low mood and depression.

Perinatal depression is considered the most common complication of pregnancy. Also known as maternal depression, it can occur during pregnancy or up to one year postpartum depression. It’s estimated that 9-16% of pregnant women are affected by depression, and that around 2–3% take antidepressants while pregnant. Another 5-7% take antidepressants after the birth. [1]

Methylfolate, a natural form of folic acid, is emerging as a promising alternative to antidepressants for pregnant and lactating women. In this blog, we will discuss how methylfolate works and its potential benefits for pregnant women with depression, and how it can be included in a prenatal care plan.  

What is methylfolate and how does it work? 


Methylfolate is the active form of folate, a crucial B vitamin required for numerous physiological processes. Also known as 5-MTHF or L-methylfolate, this form is readily absorbed into the bloodstream and can be immediately utilized in the body.

Folic acid, on the other hand, is the synthetic form of folate, and is commonly used in dietary supplements and fortified foods. Methylfolate is directly involved in the methylation cycle, a biochemical process essential for DNA synthesis, detoxification, and production of neurotransmitters.

Folate or folic acid is processed by the body through a series of enzymatic reactions. However, many people have genetic variations which impair this process, which means they cannot convert folic acid to its active form. In these cases, methylfolate supplement is recommended over folic acid. Methylfolate is the only form of folate that can bypass the multiple conversion steps, providing a direct source of active folate to be used in various metabolic processes.

Active folate is used to make S-adenosylmethionine (SAMe), a compound required for the synthesis of dopamine, norepinephrine, and serotonin. These neurotransmitters are critical for healthy mood and cognitive function. Folate deficiency may therefore result in low levels of these neurotransmitters, which can then increase the risk of depression and mood disorders. [2] SAMe is generally well tolerated, with infrequently reported side effects that include mild gastrointestinal symptoms, sweating, dizziness, irritability and anxiety.

The risks and side effects of antidepressants during pregnancy


The use of antidepressants during pregnancy and breastfeeding is somewhat controversial, as studies suggest that antidepressants can negatively affect the developing fetus. Antidepressants are monoaminergic drugs that produce neurochemicals, potentially altering the early development of the brain.

Studies have linked antidepressants to premature birth, decreased birth weight of the infant, intrauterine growth retardation, neonatal adaptive syndrome, and pulmonary hypertension. [3] Congenital heart defects, newborn adaptation syndrome, and neurodevelopment delay resulting in language impairment are also said to be a result of a mother taking antidepressants. [4]

What Does it Mean to be the “Best” Methylfolate

However, untreated depression can also have serious adverse effects on both the mother and baby. Perinatal depression can increase the risk of preeclampsia and hypertension. [5] It can also lead to postnatal depression, which can then affect the bond between mother and child.

The problem is that while herbal medicine and antidepressants may cause adverse outcomes for the pregnancy, so too does untreated depression.

The benefits of methylfolate for pregnant women with depression 


Nutritional interventions have shown promise in treating depression particularly folate.

Folate levels play an important role in the etiology of depression, and depressed individuals tend to have lower levels of folate than individuals without depression. [6]

Deficiency in folate is also associated with higher levels of homocysteine, which has also been linked to depression. [7]

In addition, genetic studies indicate that the MTHFR polymorphism C677T is more common in patients with depression.

Those with an MTHFR mutation have lower levels of active folate available for the synthesis of mood-regulating neurotransmitters, including serotonin.


Clinical trials have shown that folate may help in alleviating depression, either when taken alone or in combination with an antidepressant. [8]

Methyl folate benefits not only the mother but also the developing child. Pregnant women have a greater need for folate due to its crucial role in fetal development and growth. Folic acid is readily prescribed to pregnant women, and studies show that supplementation with folic acid can reduce the risk of neural tube defects. [9]

However, for those who cannot metabolize folic acid, folic acid may be not only ineffective but a trigger of serious health concerns. Unmetabolized folic acid syndrome (UMFA) occurs when folic acid builds up in the blood because it has not been converted into other forms of folate or flushed out of the body.

The MTHFR genetic mutation has been linked to several birth defects, including Neural Tube Defects (NTDs) affecting the brain and spinal cord due to folate deficiency. Also concerning is that unmetabolized folic acid is associated with a potentially greater risk of cancer, depression, and cognitive impairment. [10]

Researchers have noted that the presence of unmetabolized folic acid (UMFA) in cord blood can be avoided by supplementing it with the natural folate form, methylfolate. [11] A clinical trial by the University of Bonn involving 144 women showed that L-methylfolate supplement was more effective than folic acid at increasing red blood cell folate concentrations.

[13] Methylfolate is also found to be better than folic acid in maintaining red blood cell count (RBC) and plasma folate after delivery. In addition, methylfolate appears to enhance the production of or act as a substitute for tetrahydrobiopterin (an essential cofactor in neurotransmitter synthesis). [14]

Currently, there are no clinical trials on the effectiveness of methyfolate in preventing NTDs. However, studies show that methylfolate is absorbed more effectively in the body, improves folate status better than folic acid, and does not cause UMFA. [15] When comparing methylfolate vs folic acid, it is apparent that supplementation with L-methyl folate may be a better option for mothers with depression, especially in the case of MTHFR mutations.

How to incorporate methylfolate into your treatment plan?

Methylfolate supplements are becoming more readily available. However, quality varies between brands, so it's important to know how to choose a good product.

The dosage for L-methylfolate depression supplementation should be advised by an individual's health practitioner. This is particularly important for women with health conditions or known genetic disorders.

Studies involving women with MTHFR mutations who used methylfolate supplements were generally in the range of 7.5mg to 15mg/day. No adverse fetal or infant developmental outcomes have been noted. [16]

The University of Bonn study described above demonstrated that supplementation with both 208 and 416 μg methylfolate significantly decreased homocysteine and significantly increased folate levels. The authors state that the equimolar amount of 400 mcg of folic acid is 416 mcg of methylfolate. [17]

When choosing a methylfolate supplement for pregnancy, look for a scientifically formulated product that contains only pure, active ingredients. Methyl-Life® B-Methylated-II is ideal for pregnancy. It contains both the most biologically active form of methylfolate and active B12 (methylcobalamin). Vitamin B12 assists with the proper uptake and utilization of methylfolate in the body and also contributes to a healthy mood. [18]

The takeaway 


Methylfolate may be one of several natural alternatives to antidepressants for pregnant women with depression symptoms. Unlike folic acid - which is most commonly prescribed to pregnant women - an L-methylfolate supplement has not been shown to cause unmetabolized folic acid syndrome. As a natural, active form of folate, methylfolate is absorbed directly by the body and can bypass genetic mutations that impair folic acid metabolism.

Folate is essential for proper growth and development of the fetus, and methylfolate is both a safe and effective means of improving folate levels.

If you are pregnant and experiencing depressive symptoms, talk to your healthcare provider about whether methylfolate may be right for you.




















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    Written By,
    - Katie Stone



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