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Folate, also known as vitamin B9, plays a vital role in our body, supporting numerous functions. It’s essential for creating DNA, repairing DNA, and producing red blood cells. Folic acid, the synthetic form of folate, is often included in supplements and fortified foods. This nutrient is particularly important during periods of rapid growth, such as pregnancy and infancy, but it’s also beneficial throughout one’s life for maintaining overall health. Let’s explore how these supplements can contribute to your well-being.
What Is Folate And Folic Acid?
Folate and folic acid are forms of a water-soluble B vitamin that plays a fundamental role in various metabolic processes within the body. While folate naturally occurs in a variety of foods like leafy green vegetables, fruits, and legumes, folic acid is the synthetic form that’s often added to supplements and fortified foods like cereals and bread. The terms are sometimes used interchangeably, but they are not identical. Both forms of the vitamin contribute to essential biological functions such as DNA synthesis and repair, amino acid metabolism, and the formation and maturation of red and white blood cells. In the body, both folate and folic acid need to be converted to their active form, known as methylfolate, to carry out these functions effectively.
What Are The Differences In Folate Supplements?
- Folic Acid: This is the synthetic form of the vitamin, most commonly used in supplements and fortified foods. It is well-absorbed by the body but needs to be converted into the active form of folate for use.
- Methylfolate (5-MTHF or L-Methylfolate): This is the active form of folate that the body can use directly. It’s a good option for people who have difficulty converting folic acid into its active form due to genetic factors.
- Folinic Acid: Also known as 5-formyl tetrahydrofolate, this is another form of folate that’s closer to the natural form found in food. It doesn’t require the same conversion steps as folic acid but is not as readily available as folic acid or methylfolate in supplement form.
- Food-based Folate: Some supplements claim to provide folate from food sources like leafy green vegetables. These aim to offer a form of the vitamin that is similar to natural folate but are generally less concentrated.
- Combination Supplements: These may contain a mix of folic acid, methylfolate, and possibly other forms, sometimes along with other B-vitamins or nutrients.
MTHFR Gene Mutations and Dietary Supplements
What is MTHFR?
MTHFR stands for Methylenetetrahydrofolate Reductase, an enzyme that plays a critical role in converting folic acid into its active form, methylfolate. This conversion is crucial for a variety of bodily functions, including DNA synthesis and repair, as well as the regulation of homocysteine levels in the blood.
MTHFR Gene Mutations
Mutations in the MTHFR gene can impair their ability to convert folic acid into its active form, methylfolate. The extent of this impairment may differ depending on whether a person has one or two copies of the faulty gene. Having one mutated gene (heterozygous) may result in a moderate decrease in enzyme efficiency, whereas having two mutated genes (homozygous) can lead to a more significant reduction. The implications of having one versus two copies of the faulty gene can differ, as those with two copies may face a higher risk and may benefit more significantly from alternative forms of supplementation, like methylfolate.
In both cases, the body’s reduced ability to make this conversion can lead to higher levels of homocysteine in the blood. High levels of homocysteine are linked to an increased risk of cardiovascular disease, stroke, bone fractures, cognitive decline, mental health issues, and pregnancy complications.
How MTHFR Status Affects The Best Supplement Choices
For those with an MTHFR gene mutation, taking regular folic acid supplements is not as beneficial because their bodies struggle to convert it into the usable form of folate. In such cases, methylfolate supplements can be more effective, as they provide the active form of the nutrient that the body can use directly.
For people who have difficulty converting folic acid into its active form due to mutations in the MTHFR gene, taking folic acid supplements is not necessarily bad, but it may be less effective for meeting their folate needs. Because their bodies struggle to make the conversion, the unmetabolized folic acid could accumulate in the bloodstream. While the health implications of this are not entirely clear, some concerns include masking a vitamin B12 deficiency or potentially interfering with the effectiveness of certain medications.
However, it’s important to keep in mind that not everyone with an MTHFR mutation will have difficulties with folic acid metabolism. The degree of impairment can vary, and many people with these mutations do not experience noticeable symptoms or health problems.
Benefits of Methylated Forms for Those Without the Mutation
Even if you don’t have an MTHFR gene mutation, you might still find some benefits in taking methylated forms of folate. Methylfolate bypasses the need for conversion and is readily available for the body to use, ensuring efficient absorption and utilization. This can be particularly beneficial for pregnant women, older adults, or anyone who wants to ensure they are getting the most bioavailable form of the nutrient.
But for most people without an MTHFR mutation, folic acid supplements are good for meeting their nutritional needs. Over-supplementation with methylfolate can lead to other health issues, such as masking a vitamin B12 deficiency. This is why it is always a good idea to choose folate supplements that include B12. This is easy to do with a B-Complex formula.
Functions and Importance of Folate/Folic Acid
- Homocysteine Regulation: Folate helps convert homocysteine to methionine, thereby helping to regulate levels of homocysteine in the blood.
- Neural Tube Formation: In pregnancy, adequate folate levels are critical for proper neural tube closure in the developing fetus.
- Red Blood Cell Production: Folate plays a key role in the formation and maturation of red blood cells.
- DNA Synthesis and Repair: Folate is crucial for the creation and repair of DNA, essential for cell division and growth.
- Amino Acid Metabolism: Folate acts as a coenzyme for various reactions involved in the conversion of amino acids, which are the building blocks of proteins.
Consequences of Deficiency/Insufficiency
- Anemia: Folate deficiency causes megaloblastic anemia, marked by the production of large, structurally abnormal, immature red blood cells (megaloblasts). This condition impairs oxygen transport, leading to symptoms such as persistent fatigue, general weakness, shortness of breath, and heart palpitations. Additionally, affected individuals may experience pale skin, glossitis (inflammation of the tongue), and gastrointestinal symptoms like diarrhea.
- Birth Defects: During pregnancy, folate is vital for the proper development of the fetal neural tube, which forms the brain and spinal cord. Folate deficiency increases the risk of neural tube defects, such as spina bifida (incomplete closure of the spinal column) and anencephaly (major parts of the brain, skull, and scalp fail to form). These conditions can lead to severe developmental delays, physical disabilities, or even fetal mortality.
- Elevated Homocysteine: Folate plays a key role in metabolizing homocysteine, an amino acid in the blood. When folate levels are low, homocysteine levels rise, which is a recognized risk factor for heart diseases, including coronary artery disease, stroke, and peripheral vascular diseases. Elevated homocysteine is also linked to increased risks of osteoporotic bone fractures and has been studied for its potential role in renal disease.
- Cognitive Effects: Folate is crucial for brain health. Its deficiency has been linked to various cognitive impairments, including decreased concentration, slower information processing, and memory difficulties. There is growing evidence suggesting a link between low folate levels and an increased risk of neurodegenerative disorders like dementia and Alzheimer’s disease. The exact mechanisms are under investigation, but they may involve folate’s role in DNA repair and synthesis, as well as neurotransmitter metabolism.
- Mood Disorders: Folate deficiency has been associated with a higher prevalence of mood disorders such as depression and anxiety. Folate is essential for the synthesis of neurotransmitters like serotonin, dopamine, and norepinephrine, which regulate mood, emotion, and stress response. Low levels of folate can disrupt this synthesis, leading to an imbalance in these neurotransmitters and contributing to mood instability, feelings of despair, and other symptoms characteristic of depression and anxiety disorders. [PMC10490031]
Folate Food Fortification
Folic acid fortification serves dual purposes: it aids in the healthy development of newborns and contributes to heart health in the general population. Foods like cereals, flour, and bread are often fortified with folic acid to improve public health. One of the primary goals of this fortification is to prevent neural tube defects such as spina bifida in newborns, as folic acid is essential for proper neural tube formation during pregnancy. Another benefit has been the reduction of homocysteine levels in the blood, which is important for cardiovascular health. Lowering homocysteine can decrease the risk of arterial plaque formation and other cardiovascular issues.
Food Sources of Folate
|Fortified breakfast cereal
Who Is at Risk for Folate Deficiency?
- Pregnant Women: Folate is crucial for fetal development. This particularly critical at conception for preventing neural tube defects. Insufficient folate intake can pose risks to the baby.
- Alcohol Users: Alcohol interferes with folic acid absorption and metabolism, increasing the risk of deficiency.
- People on Certain Medications: Those taking drugs like methotrexate, phenytoin, or sulfasalazine may experience reduced folate absorption or increased folate depletion, putting them at risk.
- Individuals with Malabsorption Disorders: Conditions like celiac disease or Crohn’s disease can impair the body’s ability to absorb nutrients, including folate.
- Older Adults: Aging can result in decreased nutrient absorption, including that of folate. This group may also have dietary restrictions that limit folate intake.
- People with Kidney Problems: Dialysis for chronic kidney disease can remove folate from the body, requiring supplementation to prevent deficiency.
Is Folate/Folic Acid Safe?
Folate and folic acid supplements are generally considered safe and well-tolerated when taken at recommended doses. They are water-soluble vitamins, meaning any excess is usually excreted through urine, so there is almost no risk of toxicity. High doses can mask the symptoms of a vitamin B12 deficiency.
Medication Interactions with Folate/Folic Acid
- Methotrexate: This medication decreases the effects of folate, which can lead to a folate deficiency. Supplementing with folate may reduce the effectiveness of methotrexate in treating conditions like cancer.
- Phenytoin (Dilantin): This antiseizure medication can lower folate levels in the body. Taking folic acid supplements while on phenytoin may reduce the blood levels of the medication, potentially decreasing its effectiveness.
- Sulfasalazine: Often used for inflammatory conditions like Crohn’s disease, this drug may decrease the absorption of folate, increasing the risk of a folate deficiency.
- Trimethoprim: This antibiotic interferes with folate metabolism and can increase the risk of folate deficiency. Taking folic acid supplements while on trimethoprim could decrease the drug’s effectiveness.
- Antacids: Over-the-counter medications like Tums or Rolaids can interfere with folic acid absorption if taken at the same time.
- Oral Contraceptives: Birth control pills may reduce blood levels of folate. Taking folic acid supplements can counteract this effect.
- Warfarin (Coumadin): This blood thinner may interact with large doses of folic acid. High amounts of folic acid can make warfarin less effective at thinning the blood.
Supplement Interactions with Folate/Folic Acid
- Zinc: Taking large amounts of zinc can interfere with the body’s ability to absorb folic acid, potentially leading to a folate deficiency.
- Vitamin B12: While often taken together with folic acid for metabolic health, taking folic acid in isolation can mask the symptoms of a vitamin B12 deficiency, which could delay diagnosis and treatment.
- Vitamin C: High doses of vitamin C may increase the rate at which the body excretes folic acid through urine, potentially leading to lower folate levels.
- Calcium: Found in antacids and some supplements, calcium can interfere with folic acid absorption when taken simultaneously, potentially lowering the efficacy of the folic acid supplement.
- Green Tea Extract: This supplement contains compounds that can inhibit the body’s use of folic acid, affecting its potential benefits.
- Alcohol: Although not a supplement, it’s noteworthy that alcohol can severely deplete folic acid levels by interfering with its absorption and metabolism, increasing the risk of a deficiency.
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Why Supplementing With Folate Alone Isn’t Recommended
Registered Dietitians caution against taking folate supplements in isolation unless a physician recommends it for a specific folate deficiency. The reason is that extra folate can mask the symptoms of a vitamin B12 deficiency, making it harder to diagnose and treat. An ongoing B12 deficiency can lead to serious and irreversible neurological problems including dementia and nerve damage.
If one were to take a folate supplement alone, there may be no symptoms of B12 deficiency anemia. Without this, physicians could miss a crucial clue to a B12 deficiency. This could delay diagnosis and treatment, potentially leading to severe health complications. Therefore, a comprehensive approach that includes multiple B vitamins is generally recommended to both treat deficiencies and support overall health.
Vitamin B12/Methyl Folate by Vital Nutrients
Vitamin B12 and Folate work together to help maintain the health of the gastrointestinal tract, nervous system and the metabolism of protein and fats.* Both maintain homocysteine levels that are already in the normal range and folate may reduce the risk of neural tube birth defects.* This formula contains the methylated forms of B12 (methylcobalamin) and folate (Metafolin L-5-MTHF), considered to be the most bioavailable and physiologically active forms.*
- supports gastrointestinal tract health*
- promotes a healthy nervous system*
- helps maintain homocysteine levels in the normal range*
Take 1 capsule, 1-2 times daily with food, or as directed by a healthcare practitioner.
Amount Per 1 Capsule Serving
Folate Metafolin® … 1360 mcg DFE (as L-5-MTHF)(800mcg)
Vitamin B12 … 1000mcg (as methylcobalamin)
Why A B-Complex Vitamin is Often The Best Choice for Extra Folate
It is important to recognize that single-nutrient insufficiencies are rare. Usually, when a person is deficient in one nutrient, they are deficient in a number of essential nutrients. For a more comprehensive approach to health, Registered Dietitians often recommend a B-complex supplement. The B-complex supplements include not just folate and B12, but also other essential B vitamins like B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), and B7 (biotin). These vitamins work in synergy and are crucial for a variety of functions, including energy production, metabolism, and cognitive function.
Methyl B Complex by Ortho Molecular Products
Methyl B Complex is formulated with eight essential B vitamins, choline, inositol, and folate to support energy production, and immune, cardiovascular and neurological health.*
Amount Per 1 Capsule Serving
|Thiamin (Vitamin B1)
|Riboflavin (Vitamin B2 USP)
|Niacin (as Niacinamide USP)
|Folate (from 400 mcg as Quatrefolic®
|680 mcg DFE
|Vitamin B12 (as Methylcobalamin)
|Choline (as Choline Bitartrate)
Although this article discusses supplements in detail, don’t forget that we are absolutely committed to the “Food First” approach to nutrition. When it comes to your health, the totality of your eating habits far surpasses the impact of individual nutrients or any single supplement you consume. Even though this article doesn’t delve into the broader picture of your overall diet, it’s crucial to keep this element at the forefront of our minds. Your food needs to provide all the vitamins, minerals, fiber, and phytochemicals to nourish your body systems down to the cellular level.
Food choices, rather than supplements, are the most critical factors for a healthy gut microbiome. These trillions of tiny inhabitants in your gut affect your brain waves; they orchestrate your immune system. They possess the power to create molecules that can switch genes on or off and are even capable of synthesizing neurotransmitters. Opting for organic foods and steering clear of plastic packaging (including those labeled BPA-free) is a smart move to limit toxin exposure. The sum of all these parts leads to a powerful conclusion: the ultimate key to your health lies in the quality and balance of the food you consume. Supplements are secondary.
To Sum It Up
Folate and folic acid supplements offer several health benefits. These include supporting cell growth, aiding in the formation of DNA, and promoting healthy brain function. For pregnant women, these supplements are crucial in preventing birth defects. So if you’re looking to improve your health, folate and folic acid are worth considering.
This Article is Not a Substitute for Medical Advice
Dietary supplements are not designed to diagnose, treat, cure, or prevent any disease. The Supplement Sciences website seeks to provide comprehensive access to the most relevant supplement information along with convenient online ordering. We do not provide medical advice and cannot guarantee that every product suggested is completely without risk. Since each person is unique in their health history and medication use, it is important to discuss supplements with your personal physician. Specifically, pregnant women and individuals being treated for cancer or liver or kidney problems must consult their physician about every nutritional supplement they plan to take. People taking medications for the treatment of HIV or with a history of organ transplant must not take supplements without consulting with their physician.