MTHFR: The Link Between ADD/ADHD, Folate, and Genetics

MTHFR: the link between ADD/ADHD, folate and genetics

MTHFR: The Link Between ADD/ADHD, Folate, and Genetics


Attention Deficit Disorders: Do Genetics Play a Role?

ADD and ADHD are some of the most common health issues in childhood, with ADHD affecting approximately 11% of children. The symptoms of hyperactivity, impulsivity, and/or inattention associated with Attention Deficit Hyperactivity Disorder (ADHD) can affect life at home and at school with a significant impact on cognitive, academic, behavioral, emotional, and social functioning. Treatments for ADD and ADHD typically centers around stimulant medications like Ritalin and Adderall, which are associated with potentially serious side effects and don’t address the root cause of the disorders. In fact, there is growing evidence that ADD and ADHD may be associated with a genetic variation called MTHFR, which affects how folate and folic acid are metabolized in the body. Looking at the role of genetics in ADD/ADHD may shed light on promising new treatments for ADHD. 

What is MTHFR?

You may not have heard about MTHFR yet but it is a major player in many aspects of physical and emotional health. MTHFR stands for methylenetetrahydrofolate reductase and it is an enzyme that is involved in folate metabolism. Folate is a general term for a B vitamin (Vitamin B9) that comes in many forms including folic acid, which is the synthetic version commonly found in supplements and processed foods. Folic acid and folate are normally transformed by the body into Methyltetrahydrofolate (MTHF), which is the bioactive form of the B vitamin that your body needs for a variety of normal functions.

Unfortunately genetic variations in MTHFR are a big problem. Although the exact prevalence is not known, it is estimated that up to 40% of Caucasians have a mutation on one or more of the genes that normally produces the MTHFR enzyme, with varying frequencies in other populations. People who have an MTHFR variant are not able to properly process synthetic folic acid and they have a limited capacity to make MTHF.

Why is Folate So Important?

Activated folate, a.k.a. Methyltetrahydrofolate (MTHF) is an important part of something called the methylation cycle. This metabolic cycle is involved in neurotransmitter production, detoxification processes, and the regulation of inflammation. Activated folate is also needed for appropriate cell growth, which is why deficiencies in folate can lead to anemia.

Neurotransmitters are chemicals produced by the brain and nervous system that are used for communication throughout the body. These important chemical messengers include serotonin, norepinephrine, epinephrine, and dopamine, and melatonin. Neurotransmitters have potent effects on mood, energy, sleep, digestion, muscle and nerve function, memory, and cognition.

MTHFR variations have been associated with a number of health issues including mood disorders like depression, anxiety and schizophrenia, and neurobehavioral disorders like ADD/ADHD and autism. MTHFR mutations are also associated with an increased risk for heart disease, stroke, blood clots, chronic fatigue syndrome, migraines, infertility, and early miscarriage. Having an MTHFR variant may also alter someone’s response to certain medications, especially antidepressants.

Should My Child be Tested?

There is a simple blood test that your doctor can order to determine if your child has an MTHFR variant, and if so, which one. Many different labs offer this genetic testing although it is not always covered by insurance. Testing is important because depending on which (if any) MTHFR variants are found, this will help to guide treatment options. 

What is the Treatment for MTHFR?

Because MTHFR mutations are genetic there is no “cure” but luckily there are many treatments that can help reduce the health risks associated with this genetic condition. If your child has an MTHFR genetic variant talk to a physician who is knowledgeable about the condition so you may learn which specific supplement regimens may be appropriate for them.

There are also a number of simple things that you may also consider to support your child with ADD/ADHD and MTHFR:

  • Avoid Folic Acid: Folic acid is the synthetic form of the B vitamin, folate. People who have MTHFR variations can’t properly use folic acid and often don’t feel well after taking it. Many B vitamin supplements, multivitamins, energy drinks, protein bars, and processed foods contain synthetic folic acid. There are other forms of folate that are generally better for those with MTHFR including 5-MTHF, methylfolate, and folinic acid. The right dosage can vary greatly based on individual needs so talk to your physician before starting a folate supplement.
  • Folate Rich Foods: Consuming a diet of folate-rich foods including spinach, asparagus, chickpeas, beans, broccoli, and dark green leafy vegetables may be helpful for those with MTHFR. These foods naturally contain a form of folate that is more bioavailable and generally easier for the body to make use of. Rarely, people with MTHFR mutations may actually feel worse when they eat foods that are naturally high in folate, in which case you should discuss this issue with your doctor.
  • Avoid Food Additives: People with MTHFR variants tend to be more sensitive to chemicals and may have a harder time processing them and detoxifying. For this reason, avoid heavily processed foods and foods that contain heavy pesticide residues. Every year the Environmental Working Group compiles a list of foods that are highest in pesticide residues so that consumers can make healthier decisions at the grocery store. Additionally, food additives like artificial colors and sweeteners and MSG are well known to aggravate symptoms of ADD and ADHD and are best avoided.
  • Exercise: Physical activity can have amazing effects on mood and energy and may help to improve focus and attention in people with ADD/ADHD. A good goal is at least 150 minutes of moderate physical activity per week. Spending time outdoors also seems to have a calming effect on the nervous system and may help with mood.
  • Blood sugar: Keeping blood sugar balanced by limiting simple carbohydrates and processed foods can help to improve mood, energy, attention, and focus. Simple carbohydrates are found in foods like candy, cookies, baked goods, bread, pasta, cereal, white rice, and white potatoes. These foods tend to spike blood sugar levels, worsening behavioral issues and hyperactivity. Spikes in blood sugar also tend to be followed by a crash in energy and mood. Eating moderate amounts of protein foods like meat, poultry, fish, beans, lentils, eggs, cheese, nuts, and seeds can help to stabilize blood sugar levels and keep mood and energy balanced.

Find Out More About MTHFR:

First read our article (an overview): What are Folic Acid, Folate, Methylfolate, and MTHFR, and Why Is Everyone Talking About Them?

Still want more information on MTHFR and folate metabolism? Below are some websites with tons of details on MTHFR and other related genetic variations. Remember, please don’t attempt to treat yourself or your family without consulting a physician familiar with MTHFR because it is all too easy to do more harm than good.


Cori Burke, ND

Dr. Cori Burke is a Naturopathic Physician and graduate of the National University of Natural Medicine. She practices integrative primary care medicine for children and adults with a special focus on Naturopathic Pediatrics, Women's Health, and Digestive Disorders. She believes that health care should be a collaborative partnership and especially loves working with families to develop strong foundations of lifelong health. Dr. Cori currently practices at the Hillsboro Naturopathic Clinic in Hillsboro, Oregon and Love Acupuncture & Wellness Group in Clackamas, Oregon. Find out more at <a href=""></a>


  • Avatar
    Darren David Webber
    January 1, 2024 at 1:42 am

    I’ve had a working theory for a significant time, working as in being built upon over years of experience and research, that ADHD is a condition that falls under a general umbrella of conditions resulting from neuro-metabolic breakdown. Neuro-metabolic meaning the metabolic cycles which provide for neurological function. There are a list of key points regarding which contributes to this breakdown, but the primary ones are 1. Multi-generational long-term exposure to mutagenic heavy metals and petrochemical residues, which cause extensive genetic damage particularly to non-essential biological systems (those not immediately essential to continued reproduction), genetic damage which is passed on through generations and compounded. 2. Nutritional deficits due to the export of slavery practices into society at large (capitalism) and the resulting “slave diet” of processed foods with illusions of variation while providing extremely little variety in terms of natural nutrient sources (a thousand different processed meat sticks, all made from the same half-rancid ingredients, with the only differences between non-nutritional flavorings; fortified bleached white bread, with all the nutritional value stripped and replaced with a short list of supplements in toxic non-bioavailable forms). 3. Epigenetic changes occurring parallel to random genetic damages and resulting from increasing sedentarism, increasing reliance on inadequate nutrition lacking the vast majority of micro-nutritional precursors needed for metabolic cycles, and the drastic shift on the organism-as-a-species timeframe in our entire societal structure.

    Folic acid is key in that it provides from methylation cycle function, an absolutely *key* biochemical process by which methyl groups are created for use in biosynthesis of extremely important compounds, both life-essential and health-essential, with minimal methylation cycle activity resulting in just enough for life-essential functions while allowing optimal health to falter and keep people just alive — just long enough to reproduce. Methylation cycles in particular are essential for processes by which our bodies are able to repair genetic damage, including major genetic damage such as mutations resulting in cancers. We target cancer with alien treatments which bombard the entire environment of the body, while the body is inherently capable, at its best, of repairing the root cause of cancers in general — genetic damage which need not be permanent, let alone resulting in runaway proliferation of cells carrying that cause.

    My point in saying all this was to lend some credibility to this: stating that MSG is something people with ADHD have sensitivity to is proliferation of a xenophobic myth, and is demonstrably false, biochemically implausible, and … silly. Just silly. MSG is the major form of glutamic acid formed in natural fermentation processes where sodium is present, which includes some of the most significantly studied fermented foods with health benefits. Glutamic acid is essential for both excitatory and inhibitory neuro-metabolic cycles. It provides for systems of balance within our neuro-biology. It nearly impossible to consume too much. As someone with *weapons grade* ADHD, CFS, and significant narcolepsy symptoms, there are few things more beneficial than MSG, which I use in gram quantities as a supplement (usually by adding it to food instead of sodium chloride). There was a significant span of time during which ideas driving by bigotry towards Asian restaurants birthed a trend in modern pseudo-medicine which targeted “excitotoxins” and deemed MSG to be one. There’s literally not a single iota of basis for any of that in any kind of science anywhere, but it took off — because it was racially motivated. Few people understand that parmesan cheese is so rich in MSG that a bowl of alfredo pasta will likely be equivalent to numerous days eating only Chinese takeout with msg added. They saw it as a weird chemical Asians put in their food, because Asians do weird shit, like sprinkle toxins in their food. Racist utter nonsense. MSG is a healthier replacement for table salt and should be a stable world-wide, has very significant health benefits, and particularly is helpful for adhd and energy-metabolism/neuro-metabolism breakdown, as a directly available form of a key neurotransmitter and precursor to numerous other essential biochemicals, one which was far more common in historical diets rich in fermented and salt-preserved foods — one our bodies need more of for optimal function adapted for many millennia. I liked the article till I read…MSG, then facepalmed.

    • Erika Krumbeck, ND, FABNP
      Erika Krumbeck, ND, FABNP
      January 2, 2024 at 4:29 pm

      We all need to evolve as providers, and I appreciate your perspective. I agree that there may be some underpinnings of racism in the “anti-MSG” crowd. I’ve heard this MSG argument a lot lately (what you’re saying), and my feelings about MSG may have changed over the years.

      And, that said, I *have* seen patients react to it! I don’t understand how or why, but I have seen some patients get agitated or get headaches with MSG-laden foods. Maybe it is something else, and not the MSG-itself, then? I still recommend patients avoid it when doing an elimination diet, mostly because where MSG is present there are likely other artificial ingredients too.

    • Avatar
      Susan Murray
      March 20, 2024 at 10:47 am


  • Avatar
    Sara Ress Wittenberg
    December 31, 2020 at 4:37 pm

    So, can you recommend an OTC methylfolate supplement? My 7 yo had MTHFR and ADHD – doc recommended 7.5 mg 1-2x/day of Deplin, but he won’t swallow a pill…

  • Avatar
    Jenn Silcox
    May 2, 2019 at 9:57 am

    What are natural ways no meds to help my son with adhd?

  • Avatar
    V. F.
    April 17, 2018 at 4:43 am

    My son was diagnosed with ADHD last year and he’s under Ritalin right now. Last week his pediatrician ordered the MTHFR exam and it’s positive. When I asked her what to do, she said that we can’t do anything. So, my question is, how can I help my boy? Traditional medicine will only give him drugs and I don’t want that for him. Please, advice! Thank you!!!

    • Erika Krumbeck
      Erika Krumbeck
      April 20, 2018 at 6:07 pm

      Hi VF,

      That is strange. Ask your pediatrician about Deplin (also known as Metafolin). If you get stuck I recommend finding a naturopathic physician near you. You can find one at Hope this helps!

  • Avatar
    Matthew Brignall
    October 26, 2016 at 5:18 pm

    Methylation pathway stimulation is associated with real risk and unclear benefit in neurodevelopmental disorders. In Angelman’s syndrome, there was increased seizure frequency. In clinical trials, treatment increased 5-MTHF levels, but led to no symptom improvement in Rett syndrome and Angelman’s. There is also concern about methylation precursors related to cancer incidence and progression. I think the comparison with Ritalin is apt – it is a medication that is well studied, with documented risks and benefits. Deplin (or milligram doses of methylfolate in general), on the other hand, is barely studied, and much of the proposed benefits and risks are theoretical. Unknown safety is different than low risk.
    Careful with clinical anecdote – expectation bias is really strong in parents of children on the spectrum, and we’ve seen a ton of highly touted CAM or populist treatment ideas not hold up under scrutiny. See secretin, GF/CF diets, GcMAF. I recommend that anyone using biological treatments for autism read NeuroTribes and learn about the Autism Rights Together movement. For the sake of comparison, we don’t see a parallel movement for biological treatment of Down syndrome, and might find such a thing ethically challenging.

    • Dr. Erika Krumbeck
      Dr. Erika Krumbeck
      October 26, 2016 at 6:30 pm

      Hi Matt,

      Thanks for your input. (It’s always fun to have a discussion with you.)

      I hear you, there is obviously a huge difference between small case studies and clinical anecdotes and good randomized placebo-controlled trials.

      The thing is, I would expect methylfolate to increase seizure frequency. If the process of methylation increases stimulating neurotransmitters, then it would be an expected effect. But for most (not all, but most) ADHD kids – at least those who respond to Ritalin – they are under-producing stimulating neurotransmitters, which is why methylation could be helping symptoms. (This is why it often works synergistically with Ritalin or other stimulant medications.) In terms of safety, at least that ACMG Practice Guidelines at the very end of the document stated that “Because folic acid and vitamin B12 toxicities are
      rare, the risks associated with daily supplementation are low.”

      The goal of a naturopathic physician is always to find the underlying cause of the symptom or disease. This is where we get into the place where clinical medicine and evidence based medicine collide. For some kids methylfolate helps immensely. For some kids it doesn’t. If you put both groups into a double-blind placebo-controlled trial you may find no benefit, but for some kids it would have very great benefit. Is it not worth giving then? Is it not worth testing? What about for lower dosages? Is it not worth trying a GF/CF diet, if some kids might improve? These are big ethical questions. As much as I get frustrated with Britt for the abrasive way in which she is communicating these ideas, I am thankful that she is asking those questions. Because it HAS improved my practice. But I may not come to the same conclusion that either your or Britt come to.

      I have this conversation very often with my husband, who is a physical therapist. (And challenges me quite often! Matt, you’d probably like him!) At his graduation ceremony one of his professors had the best quote, which I think is a hilarious summary of this problem. “And that’s when the dog that is evidence-based medicine ran across the freeway that is clinical practice.”

  • Avatar
    Britt Hermes
    October 25, 2016 at 9:51 am

    The American College of Medical Genetics and Genomics recommends against testing for MTHFR polymorphisms.

    It is incorrect and ethically dubious to advise patients to get this test and then advertise treatments when the science suggests that doing so is useless.

    • Dr. Erika Krumbeck
      Dr. Erika Krumbeck
      October 25, 2016 at 2:34 pm

      Interesting, because here in Missoula the Neuropsych specialists (MD and PhD) have been routinely testing children with ADHD for MTHFR. (Along with a few CYP450 genes as well.) They test before starting any medication therapy, as it can predict which children are good candidates for certain medications. Most kids with ADHD, bipolar or conduct disorder diagnoses have been tested before even coming to my office. They also get their methylfolate directly from the Neuropsych’s office.

  • Avatar
    Mike J
    October 24, 2016 at 8:20 am

    Have you seen this?

    The post is by a former naturopathic pediatrician. She is saying the link between autism and MTHFR is poor and treating with methylfolate is not necessary.

    • Dr. Erika Krumbeck
      Dr. Erika Krumbeck
      October 24, 2016 at 6:18 pm

      Britt hates naturopathic physicians and all things natural medicine now. I don’t exactly consider her to be a reliable source of information since she is so biased against anything in the natural health world.

      Treating MTHFR is NOT the be-all-end-all of autism treatment. Poor methylation can lead to impairments in detoxification, reduced levels of neurotransmitters, and lower levels of CoQ10 and creatinine. It isn’t MTHFR per-se that is the problem, it is the end result that can cause issues. So for some kids adding additional methylfolate can jumpstart that process. I have seen a few kids where supplemental methylfolate was like a lightswitch – all their behavior improved, and dramatically. But not for all kids, even those with homozygous MTHFR polymorphisms. You really need to look a the totality of health, not just one tiny gene. And the risk of side effects with methylfolate is unbelievably low, much lower than treating an ADHD kid with Ritalin, for example.

      Make sense?

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