If you’ve ever laid in bed at night wondering why sleep won’t come, even when you feel tired and ready, you’re not alone. For some of us, rest doesn’t come easily — and while stress, screen time, and lifestyle play big roles, there might be something deeper at work: your genes. Specifically, how MTHFR and COMT affect sleep quality may hold important clues.
At Aya, we’re always looking for the root of imbalance. And recently, more and more people are turning to their DNA for answers. Two genes of particular interest when it comes to sleep are MTHFR and COMT, which influence how our bodies process nutrients and regulate neurotransmitters.
What is MTHFR (and How Does It Relate to Sleep)?
MTHFR stands for methylenetetrahydrofolate reductase, an enzyme that plays a key role in the body’s methylation process. Methylation is a biochemical reaction that happens billions of times per second in your cells. It helps regulate detoxification, hormone balance, cardiovascular health, and the production of neurotransmitters like serotonin, dopamine, and melatonin — all of which play roles in sleep regulation (Crider et al., 2012).
The MTHFR gene provides instructions for making this enzyme. However, some people carry genetic variants (most commonly C677T or A1298C) that reduce the enzyme’s efficiency. When MTHFR doesn’t function optimally, the body may struggle to convert folate into its active form (5-MTHF), which then slows down methylation. This can result in lower serotonin and melatonin levels, making it harder to fall asleep or stay asleep (Gilbody et al., 2007).
Additionally, impaired methylation can affect how your body clears toxins and hormones, both of which may disrupt sleep if they accumulate. While not everyone with an MTHFR variant will experience sleep issues, it can be a contributing factor, especially when combined with environmental stressors or nutrient deficiencies.
COMT: The Neurotransmitter Balancer
COMT (catechol-O-methyltransferase) is another important gene in the methylation cycle, responsible for breaking down catecholamines like dopamine, norepinephrine, and epinephrine. These brain chemicals affect alertness, focus, motivation, and the stress response. COMT uses methyl groups (the very product of MTHFR activity) to carry out this function (Tunbridge et al., 2006).
There are different versions of the COMT gene, with the most well-studied variant being Val158Met. The “Val” form breaks down neurotransmitters more quickly, while the “Met” form is slower. If your COMT enzyme is slower, stimulating chemicals like dopamine and norepinephrine may linger longer in the brain, leading to increased sensitivity to stress, anxiety, and difficulty winding down at night. This overstimulation can delay sleep onset and reduce sleep quality (Sheen & Williams, 2014).
On the other hand, those with the faster-acting COMT variant may clear these neurotransmitters too quickly, potentially resulting in low dopamine tone, fatigue, or non-restorative sleep. Understanding your COMT function can help guide sleep support strategies, particularly when it comes to stress resilience and nervous system regulation.
How MTHFR and COMT Affect Sleep Quality
The way MTHFR and COMT affect sleep quality often comes down to how well your body can balance neurotransmitters and maintain a stable circadian rhythm. These genes don’t determine your fate, but they can create tendencies — and when combined with lifestyle factors, they may influence how easily you fall asleep, stay asleep, and feel rested.
If methylation is sluggish due to MTHFR variants, serotonin and melatonin production can falter. If COMT is slow, your brain might hold onto stimulating chemicals too long, making it harder to wind down. And if it’s too fast, your body might struggle to maintain the chemical balance that supports restful sleep.
That’s why understanding how MTHFR and COMT affect sleep quality is so empowering. With insight into these genes, we can support the body in a more personalized and sustainable way.
What You Can Do to Support Better Sleep
Whether or not you’ve had genetic testing, there are simple ways to support methylation and sleep:
1. Support your methylation pathways
Focus on whole foods rich in B vitamins: leafy greens, legumes, eggs, and liver (if you like it!). For some, active forms of B12 (methylcobalamin) and folate (5-MTHF) can be helpful — especially with guidance.
2. Create sleep-friendly rituals
Dim the lights after sunset. Power down screens 1 hour before bed. Try a warm bath, herbal tea, or journaling to calm your nervous system.
3. Manage stress gently
Methylation and COMT function can both be affected by stress. Practices like breathwork, yoga, or even 10 minutes of quiet help your brain downshift.
4. Consider key nutrients
Magnesium, zinc, choline, and vitamin B6 all support the pathways that help your body make and clear neurotransmitters. A gentle supplement approach can be supportive with the right oversight.
5. Get personalized support
If sleep issues persist despite good habits, or if you feel sensitive to supplements, your genes might be offering clues. At Aya, we now offer full genomic testing to help explore how your body processes nutrients, hormones, and neurotransmitters — including MTHFR, COMT, and beyond. This can help illuminate how MTHFR and COMT affect sleep quality and guide a more tailored path to rest.
A New Lens on Rest
Our genetic blueprints don’t determine everything, but they offer a helpful lens. Understanding how MTHFR and COMT affect sleep quality opens the door to more personalized care and gentler healing.
If you’re curious about how your genes might be influencing your energy, mood, or sleep, we’re here to help. The path to deep rest might just begin with deeper insight.
Want to learn more about our genomic testing? Click here to connect with our team
References:
- Crider, K. S., Bailey, L. B., & Berry, R. J. (2012). Folic acid food fortification—its history, effect, concerns, and future directions. Nutrients, 3(3), 370-384.
- Gilbody, S., Lightfoot, T., & Sheldon, T. (2007). Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. Journal of Epidemiology & Community Health, 61(7), 631-637.
- Tunbridge, E. M., Harrison, P. J., & Weinberger, D. R. (2006). Catechol-o-Methyltransferase, cognition, and psychosis: Val158Met and beyond. Biological Psychiatry, 60(2), 141-151.
- Sheen, L., & Williams, L. (2014). Catechol-O-methyltransferase, dopamine, and sleep-wake regulation. Sleep Medicine Reviews, 18(3), 274-282.
