What Is MTHFR, and Why Should I Care?

The MTHFR gene could be the answer to your health and happiness.

B vitamins are essential for your survival, wellness, and mental health. They’re a team of nutrients that affect many systems and organs, especially your brain and heart, and you need plenty of them to get through the day. B vitamins help your body manage stress, keep a steady heartbeat, and produce energy.

So why are you feeling so tired and down even though you’re getting plenty of B vitamins through diet and supplements?

The answer could be your MTHFR gene. If yours isn’t working properly—and millions of people’s don’t—your body can’t convert B vitamins into their active form, the form that you need to get any benefit from them at all.

Luckily, as you’ll see below, there are some quick and simple ways to get the B vitamin support you need and power your best health.

How B Vitamins Keep You Happy and Healthy

There’s a direct connection between B vitamins—especially B6, B9, and B12—and mental health. That’s because your body uses B vitamins to create important brain chemicals called neurotransmitters like serotonin and dopamine.

Stacks of scientific studies show a link between B vitamin deficiencies and mental health issues like depression, bipolar, and ADHD.[1,2,3] Research shows that:

  • Vitamin B6 deficiency contributes to postpartum depression, and supplementing with B6 can help prevent it.[4]
  • Adequate vitamin B12 intake can help prevent or improve outcomes in major depressive disorder.[5]
  • People with depression have lower folate (vitamin B9) levels.[6]
  • Getting enough vitamin B6 can reduce anxiety.[7]
  • Higher intake of B vitamins reduces depression, anxiety, and stress symptoms.[8]

You can see the effects B vitamins have on mental health, and how getting enough of these essential nutrients can bring about improvements. But for some people, taking more B vitamins won’t do the trick. All because a normal biological process called methylation just isn’t happening.

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A Quick Guide to Methylation

Methylation is one of the main processes your body uses to function, taking place billions of times every minute. It converts nutrients, enzymes, and other compounds into their active forms so your body can use them effectively.

Your body needs methylated B vitamins—meaning B vitamins that have been transformed from inactive to active—to produce key brain chemicals that support a balanced mood, attention, and learning abilities. But for some people, that transformation doesn’t happen. So all the B vitamins they consume don’t do the jobs they’re supposed to.

That’s where the MTHFR gene comes into play.

What’s MTHFR?

We all have the MTHFR gene (it stands for methylenetetrahydrofolate reductase). It produces the MTHFR enzyme, a protein necessary for proper methylation. You can see “folate” right in the name, as this essential B vitamin plays a huge part in this process.

Unfortunately, up to 40% of us have an MTHFR mutation[9] that prevents conversion of B vitamins into their active forms. And, since folate and the other Bs play such a big role in mental health, those with the MTHFR mutation have a higher risk for depression, bipolar, and ADHD.[10]

When you have an MTHFR mutation, medications like antidepressants are less likely to be effective. That’s why scientists recommend that people with treatment-resistant depression have the MTHFR status tested.[11] That can be done with simple blood work, so check with your doctor about ordering them.

And once you know that you have the MTHFR mutation, you can take simple steps to work around it.

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The MTHFR Workaround: Methylated B Vitamins

What can you do when your body can’t process B vitamins properly? Take methylated (pre-processed) B vitamins.

These bioactive B vitamins fill in the missing step so your body can make full use of these essential nutrients.

One clinical trial found that patients with mood issues who took methylated B vitamins had a significant 12-point improvement in how they felt after just 8 weeks… 82% of them had a 25% reduction in dangerous homocysteine levels… and 42% achieved major breakthroughs in quality of life.[12]
A study that included 182 people with mood issues found that supplementing with methylfolate (the methylated form of folate, vitamin B9) reduced mood ups and downs by 25% in just 2 months.[13]
A meta-analysis of clinical trials found that people who weren’t getting enough relief from conventional solutions saw dramatic changes when methylfolate was added to their health regiment. The participants taking methylfolate had better responses and significantly reduced mood issues.[14]

So if you have an MTHFR mutation… and up to 40% of us do… making the simple switch to methylated B vitamins can make a huge difference for your mental health.

Get the Methylated Advantage With Just Calm

If your body struggles with methylation, Just Calm provides methylated forms of essential vitamins B6, B9 (folate), and B12. These three B vitamins work together to support neurotransmitter production and help your body manage stress effectively.

Just Calm also contains the clinically-proven psychobiotic strain, Bifidobacterium longum 1714™, for specialized mood support. This unique probiotic helps promote positive moods, restful sleep, and a balanced stress response, so you can enjoy a sense of calm positivity.

>> Discover Just Calm today to see what a difference methylated B vitamins can make.

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  1. Young SN. Folate and depression--a neglected problem. J Psychiatry Neurosci. 2007 Mar;32(2):80-2. PMID: 17353937; PMCID: PMC1810582.
  2. Mitchell ES, Conus N, Kaput J. B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci Biobehav Rev. 2014 Nov;47:307-20. doi: 10.1016/j.neubiorev.2014.08.006. Epub 2014 Aug 27. PMID: 25173634.
  3. Landaas ET, Aarsland TI, Ulvik A, Halmøy A, Ueland PM, Haavik J. Vitamin levels in adults with ADHD. BJPsych Open. 2016 Dec 13;2(6):377-384. doi: 10.1192/bjpo.bp.116.003491. PMID: 27990293; PMCID: PMC5153567.
  4. Khodadad M, Bahadoran P, Kheirabadi GR, Sabzghabaee AM. Can Vitamin B6 Help to Prevent Postpartum Depression? A Randomized Controlled Trial. Int J Prev Med. 2021 Oct 19;12:136. doi: 10.4103/ijpvm.IJPVM_240_19. PMID: 34912512; PMCID: PMC8631136.
  5. Sangle P, Sandhu O, Aftab Z, Anthony AT, Khan S. Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression. Cureus. 2020 Oct 26;12(10):e11169. doi: 10.7759/cureus.11169. PMID: 33251075; PMCID: PMC7688056.
  6. Bender A, Hagan KE, Kingston N. The association of folate and depression: A meta-analysis. J Psychiatr Res. 2017 Dec;95:9-18. doi: 10.1016/j.jpsychires.2017.07.019. Epub 2017 Jul 22. PMID: 28759846.
  7. Field DT, Cracknell RO, Eastwood JR, Scarfe P, Williams CM, Zheng Y, Tavassoli T. High-dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression. Hum Psychopharmacol. 2022 Nov;37(6):e2852. doi: 10.1002/hup.2852. Epub 2022 Jul 19. PMID: 35851507; PMCID: PMC9787829.
  8. Mahdavifar B, Hosseinzadeh M, Salehi-Abargouei A, Mirzaei M, Vafa M. Dietary intake of B vitamins and their association with depression, anxiety, and stress symptoms: A cross-sectional, population-based survey. J Affect Disord. 2021 Jun 1;288:92-98. doi: 10.1016/j.jad.2021.03.055. Epub 2021 Mar 26. PMID: 33848753.
  9. Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation. 2015 Jul 7;132(1):e6-9. doi: 10.1161/CIRCULATIONAHA.114.013311. PMID: 26149435.
  10. Cho K, Amin ZM, An J, Rambaran KA, Johnson TB, Alzghari SK. Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive Disorder. Cureus. 2017 Oct 1;9(10):e1734.
  11. Kandler CE, Lam ST. Methylenetetrahydrofolate Reductase Screening in Treatment-Resistant Depression. Fed Pract. 2019 May;36(5):207-208.
  12. Mech AW, Farah A. Correlation of clinical response with homocysteine reduction during therapy with reduced B vitamins in patients with MDD who are positive for MTHFR C677T or A1298C polymorphism: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2016;77(5):668-671. doi:10.4088/JCP.15m10166.
  13. Rainka M, et al. Effect of L-methylfolate on Depressive Symptoms in Patients with MTHFR Mutations (P3.9-057). Neurology. Apr 2019;92(15 Supplement):P3.9-057.
  14. Altaf R, Gonzalez I, Rubino K, Nemec EC 2nd. Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis. Complement Ther Med. 2021 Sep;61:102770. doi: 10.1016/j.ctim.2021.102770. Epub 2021 Aug 24. PMID: 34450256.