Home Brain & Cognition L-Methylfolate Supplements Revitalizing Your Mood, Brain, and Body, a Comprehensive Guide
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L-Methylfolate Supplements Revitalizing Your Mood, Brain, and Body, a Comprehensive Guide

L-methylfolate supplements come from a natural form of folate or vitamin B9. Recent studies have shown its potential to manage depression and other brain conditions. In this health blog, you’ll delve into all things L-methylfolate.

It includes all the information you need to make informed decisions guided by your healthcare provider:

  • Potential health benefit
  • Mechanism of action of L-methylfolate
  • Dietary sources and supplements
  • Potential side effects 
  • Recommended amount
  • Safety and precautions

What are the Potential Health Benefits of L-Methylfolate Supplements?

L-methylfolate is also known as L-5-methyltetrahydrofolate and 5 MTHF. The discovery of it can not be credited to one scientist alone. It’s a culmination of works by many scientists through the years.

On the other hand, Dr. Lucy Willis discovered folate in 1931. You can find folate in certain foods. Additionally, the folic acid synthetic form is in fortified foods, unlike L-methylfolate, which is natural. Your body, though, needs to convert folate to become L-methylfolate. Once it has been altered, your cells can use it. 

L-methylfolate helps create neurotransmitters like serotonin, dopamine, and norepinephrine. These neurotransmitters are chemicals that help control your mood.

However, you bypass the conversion step when you take l-methylfolate as a supplement. L-methylfolate undergoes a chemical reaction called methylation. This reaction makes it easier for the body to absorb and use it. You can better absorb and use it than other vitamin B9 forms with its high bioavailability. As a result, it provides various benefits based on science.

It includes improved mood and brain function and reduced risk of heart disease. Moreover, it may support the healthy brain development of babies in the womb.

1. L-Methylfolate Supplements for Mental Health Conditions

Researchers looked at 23 studies that tested folate supplements. They found that taking 5-methylfolate might help people with the following mental health conditions:

  • Depression
  • Schizophrenia
  • Autism
  • Attention deficit hyperactivity disorder 
  • Bipolar disorder

Additionally, these supplements are safe, with only a few possible side effects. However, the researchers only looked at specific types of studies and ones written in English. These results may not be relevant for everyone.

Some scientists disagree with the above findings. They found no significant effect on ADHD, autism, and bipolar disorder. However, some scientists found promising results from their schizophrenia and depression studies.

For example, researchers aimed to see if L-methylfolate could help people with schizophrenia. They gave 15 people either 15 mg L-methylfolate or a placebo for 12 weeks.

They found that the people who took the L-methylfolate had more of the active form of folate. Moreover, they exhibited fewer symptoms like negative thoughts and thinking problems. 

Brain scans also showed positive effects on brain function and structure. These affected certain parts of the brain involved in emotions. 

They suggest that L-methylfolate supplements might be a promising therapy for schizophrenia. Although, more studies are needed to confirm it.


Recent studies show that folate plays a significant role in the development of depression. Specifically, L-methylfolate has benefits when used as an add-on to usual depression medicines.

The researchers studied the effects of adding L-methylfolate to antidepressant treatment on people with major depression. They probed into nine different studies that involved over 6,700 people. 

The results showed that adding L-methylfolate supplements to antidepressants was linked to a modest improvement than taking antidepressants alone. So, adding L-methylfolate to antidepressants could help some people with major depression feel better. But more research is needed to understand how well it works.

Other researchers suggest L-methylfolate may be especially helpful for people who do not respond well to SSRI antidepressants. It may also benefit those with low folate levels. Adding L-methylfolate to usual care may provide relief from depression. Moreover, L-methylfolate may help people feel better and achieve overall wellness. 

Another study looked at 10 teenagers with depression who had already tried three different medicines without feeling better. Most of them were girls who had other mental health issues. 

Eight out of 10 girls felt better after taking L-methylfolate with their antidepressants. It improved their mood, anxiety, and irritability. It seemed like they could take the extra folate without any side effects. 

This study suggests that taking L-methylfolate supplements with antidepressants could be a safe and helpful option for teenagers. But caution must be taken because other teenagers may respond differently.

Brain Conditions

Dementia is a brain condition when people have trouble remembering things. They may find it hard to think clearly and make decisions. Moreover, they need help to do everyday activities. 

It’s not a specific condition but a general term that includes neurodegenerative diseases that worsen over time. An example is Alzheimer’s and Parkinson’s disease. Although dementia is not a normal part of aging, it usually affects older adults.

Scientists reviewed 81 studies to see the relationship between homocysteine (Hcy) and folate and their connection to dementia. They found that people with dementia had higher levels of Hcy and lower levels of folate than people without dementia.

Additionally, having high levels of Hcy can increase the risk of getting dementia. Even a tiny increase in Hcy levels can increase the risk by 9% for dementia and 12% for Alzheimer’s. This review could help healthcare providers find better ways to prevent or treat dementia.

Other researchers also found that folate might be important in how Alzheimer’s disease starts. They reviewed more than 50 studies to see how folate relates to Alzheimer’s disease. 

They found that people with low folate levels are more likely to have Alzheimer’s. But people who get enough folate in their diet or take a supplement are less likely to get Alzheimer’s. So, getting enough folate might protect the brain from developing Alzheimer’s.

2. L-Methylfolate May Support Heart Health

Folate has been linked to heart health. A study investigated whether serum folate and vitamin B12 levels are associated with heart-related death among 8,067 people with type 2 diabetes.

The study results reveal low and high serum vitamin B12 was associated with a higher risk of heart-related death. At the same time, low serum folate levels were linked with a higher risk of heart-related death.

The findings suggest that maintaining moderate serum folate levels and vitamin B12 may decrease the risk of heart-related death in people with type 2 diabetes.

A study aimed to investigate the effect of folate intake on heart disease death and all-cause death in high-risk people. They looked into 14,324 people at high risk of heart disease.

It shows moderate folate intake was linked to a lower risk of heart disease and all-cause death. In contrast, higher intake did not reduce the risk. 

Folic acid supplementation was associated with a higher risk of heart disease and all-cause death. The study suggests that modest folate intake can improve long-term survival. Moreover, excess folic acid supplementation can have potentially harmful effects on U.S. adults at high risk of heart disease.

Scientists wanted to determine if there is a link between food and heart problems in the UK. They looked at 115,664 people who were 40 to 70 years old and had no heart problems or cancer.

They asked about diet and followed the people until the end of 2018. They found that for people who ate more folate, there was a 5% lower risk of having heart disease. Additionally, they had a 10% lower risk of dying from heart disease.

3. Aide to Combat Cancer

Eating enough folate in your diet may help lower the chance of getting certain types of cancer. But it’s unclear whether taking extra folic acid supplements may help. Studies on folate, folic acid, and cancer have mixed results.

According to the National Cancer Institute, L-methylfolate may help stop cancer cells from growing. It adds “methyl groups” to specific genes that promote tumor growth. As a result, it can turn those genes off and slow or stop tumor growth.

Moreover, it can also make tumor cells more sensitive to other cancer therapies. Unlike other types of folate, L-methylfolate can cross into the brain. Hence, it could be helpful for brain tumors. Specific genes in tumors can be unstable and lead to cancer growth. L-methylfolate can help stabilize them, according to scientists.

A review shows that not getting enough folate or having low levels can increase the risk of getting certain cancers. It includes the head, neck, mouth, pharynx, esophagus, pancreatic, bladder, and cervix cancers. Inversely, folic acid supplements and more folate are linked to an increased prostate cancer risk.

Based on the review, if you don’t get enough folate and drink a lot of alcohol, it could also increase your risk of getting breast cancer. Moreover, some people might have genes that make them more likely to get cancer if they don’t have enough folate.

More research is needed to determine how much folate people need to reduce their cancer risk and if giving folate to people at high risk for cancer can help prevent it.

4. L-Methylfolate Supplements for Mother and Baby Health

Folate supplements are important for a baby’s optimal brain development. Other factors can also play a role. These factors include genes, environmental exposures, and a mother’s mental health. 

Moreover, the amount of folate supplements is still being debated by experts. They say balancing the potential benefits with the over-supplementation risks is crucial.

Overall, evidence supports the importance of maintaining adequate folate during pregnancy for a baby’s brain development in the womb.

Moreover, folate can help prevent problems in the baby’s brain and spine. Studies have shown that folate can also help prevent other issues in pregnancy, like low birth weight and preterm labor.

Babies born with heart problems may also have issues with their folate levels. Some studies suggest that taking a high dose of folic acid before and during pregnancy could help prevent certain heart defects, especially in women with a higher risk. 

So, if you’re pregnant or planning to get pregnant, it’s vital to talk to your healthcare provider about taking L-methylfolate supplements to help keep you and your baby healthy.

Folate promotes a healthy brain and spinal cord for babies. Recent research suggests that folate may also benefit the baby’s brain development later in pregnancy. It can also play a role in fetal brain development. Folate is vital for the body’s biological processes, including DNA and nervous system development. 

Maternal folate levels during pregnancy can impact a baby’s health. However, more research is needed to understand the long-term effects fully.

5. Potential Therapy for Kidney Health

Some studies reveal that folate improves oxidative stress and prevents scarring. For example, oxidative stress can cause acute kidney injury (AKI). 

A study looked into AKI on rat cells, which shows that injected 5-MTHF helps activate a protein called Nrf2. As a result, it helps the body defend against oxidative stress. 5-MTHF can help the kidneys work better and reduce oxidative stress. It also restores levels of glutathione, an antioxidant. This study suggests that taking folate supplements might help people with AKI.

On the other hand, kidney status may also affect folate levels. A study probed a survey of over 18,000 people. It looked at how kidney function impacts the folate levels in the blood. High folate levels are often seen as a sign of a healthy diet. 

However, declining kidney function also greatly affects your blood’s folate. As kidney function declines, red blood cell and serum folate levels increase. It occurs even when folic acid intake remains the same. 

It’s vital to consider kidney function as a possible confounding factor when looking at the effects of folate. In sum, the study shows that kidney function affects folate levels in the blood. It should be taken into account when studying the effects of folate.

How Do L-methylfolate Supplements Work?

Scientists suggest that the methylation of DNA and histones helps control gene expression and cell division. These are essential for a baby’s proper growth and development in the womb. Methylation is also important for brain development and function. 

But this process can produce harmful byproducts, like homocysteine. Increased homocysteine can interfere with methylation, which leads to health problems. That’s why having enough folates and other nutrients to support methylation is crucial. 

Moreover, studies show that the longer people take multiple B vitamins, including folic acid, leads to potential health benefits. It could work for stroke, brain shrinkage, cognitive decline, and depression. Folate works to counter conditions involving high homocysteine levels and inflammation.

Brain Protector

Folate and vitamin B12 are important nutrients for your brain. Many studies suggest that inflammation is linked to Alzheimer’s disease. A study shows that people who took both folic acid and vitamin B12 had a big impact on serum folate, homocysteine, and vitamin B12. It also reveals significant improvements in cognitive function and decreased inflammatory cytokines.

Additionally, according to a review, folate:

  • Counteracts Alzheimer’s development by reducing oxidative stress
  • Plays a role in DNA methylation, which is important in aging and Alzheimer’s development
  • Regulates the expression of key enzymes that contribute to amyloid plaques and brain nerve tangles formation
  • Regulates the activity of specific proteins to prevent the formation of tangles

L-Methylfolate Supplements as Mood Stabilizer

Depression can be caused by a lack of folate, which affects brain chemicals. One of these chemicals is called S-adenosylmethionine (SAMe). It can help with depression because it raises 5-hydroxytryptamine or serotonin. 

Additionally, folate, homocysteine, and SAMe are all involved in the one-carbon metabolism pathway. They are crucial for serotonin, dopamine, and norepinephrine synthesis. Abnormal levels of these brain messengers have been linked to depression and other mood disorders. Many studies show that L-methylfolate and SAMe have antidepressant effects.

Baby’s Brain Development Enhancer

Researchers believe a mother’s folate intake affects her baby’s development in the womb. They are connected to a process called C1 metabolism. It involves several pathways responsible for various biological processes. One of the pathways is called DNA methylation. It regulates gene expression, and folate deficiency can affect it negatively.

The metabolic mechanisms by which folate promotes neural tube closure and reduces neural tube defect (NTD) risk is not fully understood. Scientists think folate may affect NTD risk by influencing nucleotide biosynthesis and cell division. 

Moreover, they also attribute it to elevating homocysteine levels or changing gene expression. However, they suggest it’s likely the link between folate, genetics, and environmental factors.

Cell Growth Stabilizer

According to a review, low folate levels have been associated with a higher risk of developing certain cancers. It includes blood, lymph node, colon, breast, and prostate cancers. Poor folate status can lead to DNA breaks and changes in gene expression that increase the likelihood of cancer development. However, excessive folate intake could fuel the growth of existing cancers. 

L-Methylfolate as Heart Health Promoter

Based on a study, your body uses folate to create homocysteine. It’s a compound linked to an increased risk of heart problems. Low folate intake, impaired folate metabolism, and vitamin B-12 deficiency can cause high homocysteine levels. 

However, it’s unclear whether there is a direct link between high homocysteine levels and heart conditions. Some experts suggest high homocysteine levels can injure the inner lining of arteries. It also causes blood clots, raising your risk of a heart attack.

Where Can You Find L-methylfolate?

You can find folate in dark green leafy veggies, fruits, nuts, beans, seafood, and more. Some foods have a lot of folate, like spinach, liver, asparagus, and Brussels sprouts. 

To help prevent NTDs in babies, the U.S. and Canadian governments required food manufacturers to add folic acid. Examples are bread, cereals, pasta, and other grain products. 

Moreover, L-methylfolate supplements come in tablets, pills, powders, and liquids. You can buy them from specialty stores and online health shops. 

But is efficacy the same as folic acid supplements? L-methylfolate can be equally or may even be better than folic acid. A study aimed to see if L-5-methyltetrahydrofolate (L-5-MTHF) worked as well as folic acid, at raising folate levels in Malaysian women. 

The results show that both folic acid and L-5-MTHF raised folate levels. Moreover, both lowered homocysteine levels. But those who took L-5-MTHF had even higher folate levels than those who took folic acid. So, L-5-MTHF could be a good option for people who need more folate. But more studies are required to see if it also works for everyone.

Take note that there are also different formulations. Those with “6S” and  “L” methylfolate are more biologically active than those with “R” and “D.” Moreover, some brands have add-on vitamin B12 as a cofactor for increased potency.

What are the Side Effects or Risks?

Potential side effects involve stomach upset. It includes nausea, gas, and bloating. 

L-methylfolate can also cause other side effects that you should be aware of. These side effects may include difficulty concentrating, irritability, and confusion.

An allergic reaction can happen. Be mindful of the symptoms like rashes, difficulty breathing, and swelling of the face, mouth, or throat. It’s important to talk to your healthcare provider immediately if you experience these side effects.

If you are not yet taking it, speak with your healthcare provider to determine whether the benefits of L-methylfolate supplements outweigh the possible risks and side effects.

How Much to Take and When?

There are varying doses depending on who’s taking the supplement. At the same time, amounts differ for folate, folic acid, and L-methylfolate. Manufacturers offer 7.g mg and 15 mg daily for L-methylfolate.

The usual folate intakes from foods are:

  • 417 to 547 µg for children
  • 602 µg for adult males
  • 455 µg for adult females

In contrast, healthcare providers recommend folic acid supplements with the following doses:

200 to 400 micrograms (µg) for children 

400, 600, or 800 µg per day for pregnant women

It is unclear whether higher folate intake is beneficial or harmful for pregnant women. More research is needed to understand the optimal dose range and timing of folate intake during pregnancy. Generally, it is best to talk to your healthcare provider regardless if you are pregnant or not.

Is L-methylfolate Safe?

L-methylfolate supplements are generally safe at a maximum of 15 mg daily. Some healthcare providers suggest a month trial period to see how your body reacts to it. Taking too much of it may lead to likely side effects and other issues.

Not getting enough Vitamin B12 in your diet can lead to anemia and thinking problems. Healthcare providers may recommend folate supplements to fix anemia. But some experts worry that too much folate might hide the fact that a body needs more Vitamin B12 until it’s too late. 

Additionally, taking too much folic acid may also raise the risk of certain cancers. It might also affect how a baby’s brain develops if a pregnant woman takes more than 1,000 mcg of folic acid a day. 

Studies found that unmetabolized high doses of folic acid can accumulate in the body. As a result, there may be fewer natural killer cells that help fight illness. It might also lead to thinking problems for older adults. 

Who Should Not Take L-methylfolate?

It is vital to inform your healthcare provider if you have had an allergic reaction to L-methylfolate. Pregnant and breastfeeding women and kids should only take it if specifically recommended by a healthcare provider.

Inform your healthcare provider if you have an absorption problem. It’s because your body might not be able to absorb L-methylfolate. Additionally, it’s best to avoid antacids, dairy products, tea, or coffee. These foods may affect the action of L-methylfolate. Drinking excessive alcohol can also reduce its absorption. It may worsen side effects like drowsiness and stomach upset. 

Keep your healthcare provider informed about your health condition and any other medicines you are taking to avoid any potential side effects.

Interactions with Medicines

According to experts, it may interact with pafolacianine, fluorouracil, and capecitabine. Surgeons use pafolacianine to help find and remove ovarian cancer during an operation.  This special medicine may not work if you take L-methylfolate within 48 hours of surgery.

Anti-cancer drug fluorouracil, when combined with L-methylfolate, may cause serious side effects. It includes anemia, bleeding, risk of infections, and nerve damage. Another cancer therapy drug, capecitabine, can become more potent when combined with L-methylfolate. It may also cause similar side effects as fluorouracil. 

Additionally, L-methylfolate interacts with antiepileptic drugs and sulfasalazine for ulcerative colitis. Antiepileptic drugs lower folate levels, while sulfasalazine can cause folate deficiency.

For safety reasons, inform your healthcare provider if you take medicines or herbal supplements. 

Frequently Asked Questions

Question 1: Is L-methylfolate the same as folic acid?

No, L-methylfolate supplements come from an active form of folate that the body can directly use. In contrast, a folic acid is a synthetic form that needs to be converted to methylfolate before it can be used. Taking methylfolate supplements may be more effective.

Question 2: Who should take L-methylfolate?

L-methylfolate supplements are usually given to people with certain medical conditions that prevent their bodies from properly absorbing or using folic acid. Additionally, healthcare providers may recommend it for pregnant women, as it plays an important role in the baby’s development. However, speaking with your healthcare provider for proper guidance is essential.

Question 3: Can L-methylfolate be taken during pregnancy?

L-methylfolate supplements are considered safe for pregnant women. It helps prevent certain birth problems. But, it is vital to consult your healthcare provider before taking L-methylfolate or any other supplement during pregnancy to determine the appropriate dosage and ensure it is safe for you and your baby.

Final Thoughts

So there you have it – all you need to know about L-methylfolate supplements and their potential benefits! L-methylfolate is a versatile and natural way to promote optimal health.  Experts suggest it supports your mood, brain, heart health, and more.

There may be possible side effects and precautions. But L-methylfolate can be a safe and effective addition to a daily routine with the right dosage and guidance from a healthcare professional.

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