The MTHFR gene has become one of the most talked about genetic variations in integrative health spaces – and one of the most misunderstood. It is not a diagnosis, not a guarantee of future illness, and not a reason to panic. But it is good to be aware of it!
In this article, we’ll walk through what the MTHFR gene does, how it relates to methylation and folate metabolism, what common variants can (and can’t) tell us about health, and what parents need to know when supporting their children.
What Is the MTHFR Gene?
MTHFR stands for methylenetetrahydrofolate reductase. The term is used to describe both the MTHFR gene and the enzyme it encodes (1,2). A gene is a segment of DNA that contains instructions for making a specific protein or enzyme. Small variations in a gene’s DNA sequence – called single nucleotide polymorphisms (SNPs) – are common and represent normal genetic diversity. These variants do not change what the gene does, but they can influence how efficiently the resulting enzyme functions.
The MTHFR gene provides instructions for making the MTHFR enzyme (1,2), which plays a role in folate metabolism. Specifically, this enzyme helps convert folate into 5-methyltetrahydrofolate (5-MTHF), a form required for key biochemical processes, including methylation. Methylation is one of the pathways that relies on this conversion. When MTHFR enzyme activity is reduced, the pathway may function less efficiently.
What Is Methylation – and Why Does It Matter?
When discussing MTHFR, methylation comes up because a primary role of the MTHFR enzyme is to support this pathway. Methylation is a normal essential biochemical process that occurs in every body every day. It involves the transfer of small chemical groups (methyl groups) that help regulate and drive countless reactions throughout the body (3).
MTHFR matters because it helps supply one of the key inputs needed for this process to run efficiently. Through methylation, the body supports functions such as:
- DNA building and repair
- Neurotransmitter production (including serotonin and dopamine)
- Hormone metabolism and clearance
- Immune cell development and regulation
- Detoxification pathways, including glutathione production
- Energy production at the cellular level
When methylation pathways are working optimally, the body tends to adapt more effectively to both internal and environmental stressors. When methylation capacity is reduced (whether due to genetics, nutrient availability, or overall physiological load), certain systems may become more sensitive or require additional support.
What Does “Having an MTHFR Variant” Mean?
Having a genetic “mutation,” more accurately called a variant, simply means there is a difference in the gene’s code. MTHFR variants are common in the general population (4) and, on their own, do not diagnose or predict disease. The two most discussed MTHFR variants are:
- C677T
- A1298C
Each person inherits two copies of the MTHFR gene – one from each parent. This is where the terms heterozygous and homozygous come in (4):
- Heterozygous means there is one altered copy of the gene and one typical copy.
- Homozygous means there are two altered copies of the gene.
The number of altered copies can influence how efficiently the MTHFR enzyme functions. In general, having one copy of a variant may result in a mild reduction in enzyme activity, while having two copies is associated with a greater reduction in activity (4). It is important to note that health is influenced by countless factors, and your MTHFR status is just one small piece of the puzzle.
Lifestyle, nutrition, sleep, stress, and many other health factors play a role in the overall health landscape. This is why two people with the same MTHFR result can look completely different clinically.
How MTHFR Can Show Up in Kids
About half of the population has an MTHFR variation (4). Most children (and adults) with an MTHFR variant are healthy! However, in some cases, particularly when combined with other stressors, reduced methylation efficiency may contribute to patterns such as:
- Increased sensitivity to stress
- Mood or emotional regulation challenges
- Attention or focus difficulties
- Recurrent infections
- Allergic tendencies
- Difficulty tolerating synthetic vitamins or fortified foods (more on this below)
How Is MTHFR Tested?
If you’d like to know your or your child’s MTHFR status, you can do so through testing. Testing for MTHFR is straightforward and widely available. It is typically done using:
- A blood test or
- A cheek swab
Some conventional providers or pediatricians offer this testing, though insurance coverage can vary, and conventional medicine does not always put much weight into these results, especially in the absence of other glaringly obvious health issues.
Integrative practitioners often evaluate MTHFR results alongside additional markers to better understand how the gene may be functioning in the body, such as:
- Folate and vitamin B12 status
- Homocysteine levels
- Overall nutrient balance
Looking at symptoms and overall health along with these markers helps place genetic findings into a broader health context.
Folate and MTHFR
Because the MTHFR enzyme plays an important role in folate metabolism, folate supplementation often becomes part of the conversation when an MTHFR variant is identified. This is where confusion tends to arise, particularly around which forms of folate are appropriate.
Understanding the Different Forms of Folate (and When Each One Makes Sense)
Not all folate is the same. Below we’ll be discussing some common forms.
Folic Acid (Synthetic Folate)
Folic acid is a synthetic form of folate that does not occur naturally in food. It is commonly added to:
- Fortified breads, cereals, and grains
- Many conventional multivitamins and prenatals
Folic acid must go through several conversion steps before becoming usable. For individuals with reduced MTHFR activity, this process may be less efficient (5). Unmetabolized folic acid has been detected in the bloodstream with high intake (6), which is why many integrative practitioners recommend avoiding supplemental folic acid, especially when an MTHFR variant is known.
Natural Food Folate
Naturally occurring folate is found in whole foods such as:
- Leafy greens (spinach, kale, arugula)
- Broccoli and other cruciferous vegetables
- Avocado
- Legumes and lentils
- Asparagus
Food-based folate is gentle, balanced, and packaged with complementary nutrients. For most children, this is great – regardless of genetics!
Looking for ways to sneak more greens into your kid’s diet? Check out this recipe! Green Pancakes For Picky Eaters
Methylfolate (5-MTHF)
Methylfolate is the fully active form of folate and does not require conversion by the MTHFR enzyme. For many individuals, this makes it a well-tolerated and effective option for supporting methylation and overall folate status.
Folinic Acid (5-Formyl-THF)
Folinic acid is a bioactive form of folate that also bypasses the need for conversion from folic acid, but it enters folate pathways in a more gradual way. For some individuals, folinic acid may be a better fit. For example:
- When a gentler approach to folate support is preferred
- For children who are more neurologically or metabolically sensitive
- As a starting point when introducing folate support
What Can Parents Do If an MTHFR Variant Is Present?
If your child is healthy, happy, and not experiencing any difficulties, you probably do not need to do a big routine overhaul just because you discover a MTHFR SNP. That said, the tips below are good general practice for everyone, especially those with known MTHFR variations:
- Prioritizing whole-food folate sources
- Limiting synthetic folic acid in supplements and food when possible
- Supporting gut health for nutrient absorption
- Reducing unnecessary chemical and toxin exposure
- Ensuring adequate protein and micronutrient intake
- Supporting sleep, stress regulation, and blood sugar balance
- Support nutrient balance through thoughtful supplementation
A Note on Reducing Synthetic Folic Acid in Food & Supplements
Synthetic folic acid is commonly added to processed and fortified foods and is also found in many conventional supplements. Unlike naturally occurring food folate or bioactive folate forms, folic acid must first be reduced and metabolized before it can enter normal folate pathways in the body. Studies have shown that when folic acid intake is high, a portion of folic acid may remain unmetabolized in the bloodstream (6). This appears to reflect limits in the body’s capacity to process large amounts of synthetic folic acid at once.
Pay attention to labels of processed foods, especially those containing grains like cereals and store-bought bread. You’ll notice that many of these products include folic acid as an ingredient.
To learn more about processed foods, read this article: Ultra-Processed Foods: What Are They, & How Are They Affecting Kids?
For individuals with reduced efficiency in folate metabolism – including some people with MTHFR variants – this conversion process may be less efficient (5), making overall folate form and total intake particularly relevant.
A Note on Laughing Gas and MTHFR
Laughing gas (nitrous oxide) is commonly offered during routine procedures, such as dental work. One additional consideration for individuals with known MTHFR variants is that nitrous oxide can temporarily inactivate vitamin B12 (7), which plays an important role in methylation and homocysteine metabolism.
To learn more, read this article: Detoxing Kids From General Anesthesia: A Guide for Parents
For most people, occasional exposure is unlikely to cause issues. However, in children with known methylation vulnerabilities or low B12 status, this temporary effect may be more relevant. This doesn’t mean laughing gas must always be avoided, but it does mean it’s reasonable to:
- Inform your provider of known MTHFR variants
- Ensure adequate B12 status, especially if nitrous oxide is used
- Discuss alternative options when appropriate
A Note On Folic Acid Supplementation During Pregnancy
While this article is mostly about MTHFR in kids, I want to make a note that adequate folate intake during pregnancy is essential, particularly in early pregnancy, due to its role in neural tube development. This is why folate supplementation is widely recommended for those who are pregnant or trying to conceive. Where confusion often arises is around the form of folate used.
Folic acid is the synthetic form of folate most commonly included in conventional prenatal vitamins and fortified foods. While many individuals can convert folic acid into its active form, we know that this process may be less efficient in individuals with MTHFR variants. For this reason, many practitioners now recommend bioactive folate forms, such as methylfolate or folinic acid, during pregnancy instead of folic acid. These forms do not require the same conversion steps and may be better utilized by the body.
To learn more about choosing a prenatal vitamin, read this article: What To Look For In A Prenatal Vitamin
Summary
The MTHFR gene plays a role in how the body processes folate and supports methylation. Variations in the MTHFR gene are common. For most children (and adults), an MTHFR variant may go unnoticed, but in some cases – particularly when combined with other stressors such as nutrient deficiencies, chronic stress, illness, or environmental exposures – reduced efficiency in folate metabolism may contribute to increased sensitivity in certain systems. Understanding MTHFR is less about fixing genetics and more about supporting the body’s needs. This often means prioritizing whole-food folate sources, being mindful of synthetic folic acid intake, supporting overall nutrient balance, and using bioactive folate forms thoughtfully when appropriate.
References:
- Araszkiewicz AF, Jańczak K, Wójcik P, Białecki B, Kubiak S, Szczechowski M, Januszkiewicz-Lewandowska D. MTHFR Gene Polymorphisms: A Single Gene with Wide-Ranging Clinical Implications-A Review. Genes (Basel). 2025 Apr 8;16(4):441. doi: 10.3390/genes16040441. PMID: 40282401; PMCID: PMC12027316.
- Leclerc D, Sibani S, Rozen R. Molecular Biology of Methylenetetrahydrofolate Reductase (MTHFR) and Overview of Mutations/Polymorphisms. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6561/
- Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013 Jan;38(1):23-38. doi: 10.1038/npp.2012.112. Epub 2012 Jul 11. PMID: 22781841; PMCID: PMC3521964.
- Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998. L, Methylenetetrahydrofolate Reductase. Available from: https://www.ncbi.nlm.nih.gov/books/NBK114334/
- Vidmar Golja M, Šmid A, Karas Kuželički N, Trontelj J, Geršak K, Mlinarič-Raščan I. Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate. J Clin Med. 2020 Sep 2;9(9):2836. doi: 10.3390/jcm9092836. PMID: 32887268; PMCID: PMC7564482.
- Tam C, O’Connor D, Koren G. Circulating unmetabolized folic Acid: relationship to folate status and effect of supplementation. Obstet Gynecol Int. 2012;2012:485179. doi: 10.1155/2012/485179. Epub 2012 Feb 19. PMID: 22529856; PMCID: PMC3317000.
- Campdesuner V, Teklie Y, Alkayali T, Pierce D, & George J. (2020). Nitrous Oxide-Induced Vitamin B12 Deficiency Resulting in Myelopathy. Cureus, 12(7), e9088. https://doi.org/10.7759/cureus.9088
