Methylation and Women’s Health

By Suzanne Fenske, MD, FACOG, ABOIM, MSCP

Methylation and Women’s Health

Methylation is happening right now, in every cell of your body. It’s critical for pregnancy, estrogen detoxification, longevity, and overall health. But what exactly is methylation, and what do women, specifically, need to understand to optimize their health and hormones?

If you have an MTHFR mutation, estrogen dominance, or are in perimenopause, this article is for you. Keep reading as we explore and understand:

• What is methylation?
• Methylation nutrients
• Genetics and epigenetics
• Methylation’s role in hormonal balance and women’s health concerns
• How to support balanced methylation with integrative medicine

What is Methylation?

A methyl group is a carbon atom attached to three hydrogens (CH₃), and methylation is the process of adding a methyl group to a molecule, such as a hormone or enzyme. Often referred to as one-carbon metabolism, methylation is an essential biochemical process that occurs in every cell of the body. It happens billions of times per second, and most of us don’t give it a single thought.

Methylation is necessary for many key biochemical reactions in the body, including:

• Detoxification (including estrogen and endocrine disruptor detoxification)
• Neurotransmitter production
• Genetic expression (more on this below)
• Amino acid (protein) metabolism
• Growth and development (including pregnancy)
• Producing phosphatidylcholine for cell membranes
• Producing creatine for muscle health and strength
• Producing glutathione for antioxidant protection

The methylation process requires specific nutrients to produce methyl groups. The primary nutrients are folate (vitamin B9) and vitamin B12. Deficiencies in these nutrients lead to under-methylation. Other critical nutrients include methionine (from protein), choline, riboflavin (vitamin B2), niacin (vitamin B3), pyridoxine (vitamin B6), magnesium, and others.

In addition to nutrition, methylation is influenced by:

• Exercise and movement
• Stress
• Sleep
• Gut and microbiome health
• Toxin/pollution exposure
• Alcohol use
• Health status
• Genetics

Methylation, Genetics, and Epigenetics

For some, genetics play a role in how the methylation cycle in cells functions. Individuals may have specific genetic mutations known as single nucleotide polymorphisms (SNPs). These are small changes in the genetic code.

You may be familiar with MTHFR (5,10-methylenetetrahydrofolate reductase). This gene codes for the MTHFR enzyme, a key enzyme in the methylation cycle. Specific SNPs in the MTHFR gene affect about 50% of people and may impact how the enzyme functions. While SNPs don’t cause disease outright, MTHFR polymorphisms are associated with:

• Autism Spectrum Disorder
• Fertility issues
• Neural tube defects
• Depression
• Metabolic disorders, including diabetes
• Certain cancers
• Autoimmune diseases

The good news is that genetics isn’t the whole picture; epigenetics, or the expression of genes, also plays a role. Modifiable factors, including diet and lifestyle, influence epigenetics. So, it’s possible to have perfect genetics but poor methylation or methylation SNPs but balanced methylation.

There’s one more piece to this story; methylation is critical for epigenetic expression. Methylation of the DNA itself turns on specific genes.

Methylation and Women’s Health

Changes in DNA methylation occur with age and affect reproduction and long-term health. Some research suggests that methylation regulates the onset and duration of perimenopause in women. If this is the case, optimizing methylation might help ease the perimenopausal transition.

Estrogen, specifically estradiol, the primary reproductive estrogen, plays a significant role in balancing DNA methylation, thereby positively affecting genetic expression. Some research suggests that menopausal women taking hormone replacement therapy (HRT) may have better methylation patterns in menopause, possibly reducing cardiovascular disease risk.

Furthermore, optimal methylation is crucial for detoxifying estrogen through the liver via the COMT (catechol-o-methyltransferase) enzyme. COMT SNPs, inadequate nutrient cofactors, or a sluggish liver can slow this process, contributing to higher levels of circulating estrogen. For this reason, and others, poor methylation status may contribute to:

• Estrogen dominance – High estrogen relative to progesterone, can cause symptoms such as PMS, breast pain, heavy periods, and more
• PCOS – Changes in DNA methylation patterns may be an underlying mechanism in PCOS
• Endometriosis – Changes in DNA methylation patterns may be an underlying mechanism in endometriosis

Of course, methylation isn’t the only factor affecting these conditions, but it’s one to consider, as it helps explain why certain dietary patterns and lifestyle choices contribute to or alleviate symptoms.

After menopause, women’s risk of chronic disease increases, and while women tend to live longer than men, they often spend more years in poor health. Improving methylation may help improve longevity and healthspan. Although this study was in men, following nutrition and lifestyle interventions to support healthy DNA methylation decreased participants’ biological age.

How to Support Balanced Methylation

When it comes to methylation, more isn’t always better. While the most common issue is under-methylation due to an increased need for specific nutrients, poor lifestyle, and toxin exposure, over-methylation can also cause symptoms. If you are sensitive to methylfolate supplements, you might be an over-methylator.

Here are some ways to promote and balance methylation:

• Eat whole foods. Build your diet around whole or minimally processed ingredients, including vegetables, fruit, high-quality protein, healthy fats, nuts, seeds, legumes, and whole grains.

• Consume optimal methylation nutrients, including vitamin B12, folate, and choline. Food sources include:
  • Vitamin B12 – High-quality animal foods (meat, fish, eggs, dairy)
  • Folate – Dark leafy green vegetables, legumes, avocados, citrus
  • Choline – Eggs, fish, soy, beets * while liver is a source of choline we don’t recommend routinely eating it to meet daily needs

The TārāMD nutrition team can work with you to ensure you are meeting your daily nutrient requirements.

• Eat “methyl adaptogens,” a term coined by Dr. Kara Fitzgerald, who has found that specific high-phytonutrient plant foods help modulate DNA methylation and promote a younger biological age. These include: 
  • Green tea
  • Oolong tea
  • Turmeric
  • Rosemary
  • Garlic
  • Berries

• Use targeted supplements. More nutrients aren’t always better, but well-placed supplements can help fill dietary gaps or support increased requirements for specific nutrients. It’s essential to use the correct forms of B vitamins and other nutrients. You can also supplement with creatine or phosphatidylcholine, which helps free up methylation for other purposes in the body. Please work with your TārāMD provider for personalized guidance.

• Work with TārāMD. With so much nuance and individuality, methylation isn’t something to play with on your own. If you’re curious about your methylation status, genetics, and how they all relate to your health concerns, we can help. For example, if you are taking bioidentical estrogen, let’s ensure you’re also detoxifying it, which requires good methylation status.

When you zoom in, methylation research provides clues to women’s health conditions, the reasons they occur, and potential diagnosis and treatment strategies. When we zoom out to look at the big picture, a nutrient-dense diet and healthy lifestyle habits promote healthy methylation. So, when you drink the green smoothie, meditate, or lift weights, you’re not only supporting your health goals, but also your methylation.

References

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