Fertility Optimization with Epigenetics

When it comes to fertility, your genes can provide valuable insight into what diet and nutrients are critical for you.

More and more people are electing to test either specific genes, or to have their entire genome sequenced. However, as we learn more about the genome, it is no longer sufficient to attribute health concerns to just your genes. Genetically identical twin mice, for example, can look entirely different in both color and size, by manipulation of epigenetics. Epigenetics are environmental effects that can turn genes on or off. Epigenetics include diet, lifestyle and nutrients to name a few (1). Your genes do not have to be your destiny. Armed with data on your genome, it is possible to optimize  expression of genes using targeted dietary and nutraceutical interventions. This article supports women optimize fertility using epigenetics.

Gene #1 MTHFR

If there is one gene I recommend knowing about yourself, it is this one!

MTHFR, or methylenetetrahydrofolate reductase, provides information about your ability to methylate, which is a process that turns on or off every other gene. A genetic mutation in this gene may lead to low levels of folate and other vitamins, and high levels of homocysteine in the blood.

High homocysteinene levels are associated with heart disease, neurological disorders, cleft palate, infertility and neural tube defects to name a few.  The optimal number for homocysteine is 7 micro moles per liter. Having levels that are higher or lower provide challenges to methylation.  High homocysteine is a risk factor for unexplained infertility, miscarriage, and preeclampsia, a pregnancy complication characterized by high blood pressure (1).

A deficiency in methylation can contribute to neural tube defects and congenital defects in infants. This can be prevented using folate, a B-vitamin that is naturally found in green, leafy vegetables. Beware the artificial form of folate, folic acid, which is found in vitamin pills and as an additive in processed food. Folic acid has the potential to get into your folate receptors, blocking natural folate from entering cells, further inhibiting your body from methylating (2).

If you have a genetic mutation in MTHFR, consider the following to optimize your ability to methylate:

  • About 85% of methylation occurs in the liver, so show love your liver as much as possible! Limit your exposure to alcohol, food colorings, flavorings,  preservatives and pesticides, which are chemicals that make the liver work harder.
  • Exercise has been found to promote new patterns of methylation. However, be mindful of over-exercising as this may stress your body and disrupt healthy methylation.
  • Antacid use, heavy metals, viral infections, bacterial and yeast overgrowth challenge your ability to methylate. If any of these are current health concerns consult a naturopathic doctor and treat the underlying cause.
  • Optimize your intake of methylfolate (B9), riboflavin (B2), and methylcobalamin (methylated vitamin B12)
    • Supplementing with high-dose methyl donors, like vitamin B12 outside of your prenatal vitamins should not be continued long-term. Supplements are to be used to get you back into a range that can be maintained with diet and lifestyle.

Gene #2 COMT

This gene provides an indication of your ability to process estrogen and some neurotransmitters.  COMT breaks down the neurotransmitters dopamine, epinephrine and norepinephrine, which are part of your “fight or flight” response when your body responds to stress.

The COMT gene plays a crucial role in estrogen metabolism. Mutations in this gene are linked to the development of Premature Ovarian Insufficiency and preeclampsia. In males, abnormalities can alter testicular cells and male fertility (2).

The COMT enzyme is found in high levels in the liver, kidney, endometrium, breast and granulosa cells. Reduced COMT activity increases the risk of hormone-dependent diseases by enhancing levels of estrogen, accumulation of catechol estrogens and subsequent oxidative DNA damage (3).

If you have a mutation in COMT here’s what you can do:

  • Prioritize stress management and self-care. Mutations in COMT limit the ability to metabolize and remove stress hormones by 3-4 times. Consult with a naturopathic doctor to test your salivary cortisol across the day and optimize your stress response.
  • Limit exposure to endocrine disrupting chemicals. Estrogenic plasticizers, such as BPA and BPB inhibit COMT activity in vitro (5). For more information, view my blog on “Tips for Reducing Exposures to Endocrine Disrupting Chemicals”
  • Mercury inhibits COMT activity. Restrict exposure to mercury, which is commonly found in large fish such as Tuna.
  • Have daily bowel movements to support elimination of excess estrogens and toxins such as mercury
  • Limit caffeine, alcohol and smoking to reduce oxidative stress.
  • Consider limiting strenuous exercise. Exercise requires methylation and increases catechols.
  • Fasting can increase catechols. Eat regularly to maintain blood sugar levels and avoid insulin spikes.

Gene #3 DAO

A mutation in this gene manifests as an oversensitivity to histamine. Histamine regulates immune response, gut function, and acts as a neurotransmitter, affecting thought and emotion. Symptoms of an issue with this gene can include feeling abdominal pain, itchy, or sweaty after eating, especially if eating fermented foods or left overs.

If you have a mutation in this gene, it is especially important to have a strong intestinal lining and treat leaky gut, which is a condition when the intestinal lining is weak and allows partially digested matter into the bloodstream, triggering an immune response.

The balance between histamine and DAO seems to be crucial for an uncomplicated course of pregnancy. Reduced DAO activities have been found in complications of pregnancy including: diabetes, threatened and missed abortion and trophoblastic disorders. Low activities of the histamine-degrading enzyme DAO might indicate high-risk pregnancies (5).

What to do:

  • Heal your gut. Assess food allergies and sensitivities and follow an elimination-provocation protocol. Consider foods such as collagen, colostrum or glutamine to support and heal the intestinal lining.
  • The DAO enzyme is dependent on vitamin B6, B12, iron, copper and vitamin C. If you are symptomatic for elevated histamine, assess and treat nutrient deficiencies with a licensed naturopathic doctor.
    • Intake of vitamin B6 leads to a higher DAO activity. The NIH recommends a maximum dose of 2 mg for lactating mothers. 
    • Copper is a central atom of the DAO and thus essential for its function. It’s not often recommended to supplement copper. Foods to optimize copper intake include: sunflower seeds, lentils, almonds, asparagus, turnip greens. 
    • Vitamin C can be taken at doses of up to 3,000 mg to reduce histamine levels. Discuss the right dose for you with your doctor
  • Magnesium is important in the histamine metabolism. 

Supplement dosing is personalized based on your lifestyle, age, and weight. Do not take supplements without consulting a doctor. Excess Vitamin B6 for example, can cause nerve damage. For more information on whether genetic testing or certain supplements may be right for you, schedule an appointment.


  1. Adams, J. (2008) Obesity, epigenetics, and gene regulation. Nature Education 1(1):128
  2. Lynch, Ben. Dirty Genes: a Breakthrough Program to Treat the Root Cause of Illness and Optimize Your Health. HarperOne, an Imprint of HarperCollinsPublishers, 2018.
  3. Cordts, Emerson, et al. “COMT Polymorphism Influences Decrease of Ovarian Follicles and Emerges as a Predictive Factor for Premature Ovarian Insufficiency.” Journal of Ovarian Research, vol. 7, no. 1, 2014, p. 47., doi:10.1186/1757-2215-7-47.
  4. Skowron, Jared M. “Move Over, MTHFR: Time to Look at COMT.” Naturopathic Doctor News and Review, Naturopathic Doctor News and Review, 25 Apr. 2018, ndnr.com/pediatrics/move-over-mthfr/.
  5. Ho PW, Tse ZH, Liu HF, et al. Assessment of Cellular Estrogenic Activity Based on Estrogen Receptor-Mediated Reduction of Soluble-Form Catechol-O-Methyltransferase (COMT) Expression in an ELISA-Based System. PLoS One. 2013;8(9):e74065.
  6. Maintz, L., et al. “Effects of Histamine and Diamine Oxidase Activities on Pregnancy: a Critical Review.” Human Reproduction Update, vol. 14, no. 5, 2008, pp. 485–495., doi:10.1093/humupd/dmn014.
  7. “DAO Deficiency and Histamine: The Unlikely Connection.” MTHFRSupport Australia, 5 Nov. 2019, mthfrsupport.com.au/2016/09/dao-deficiency-and-histamine-the-unlikely-connection/.

"This blog is not intended to provide a health diagnosis, treat a medical condition, or provide medical advice. All content provided on this blog is for informational purposes. No action should be taken solely on the contents of this blog. Consult your doctor with any questions or for medical advice."