Today’s edition is covering one of the most important topics regarding menopause symptoms and overall health and well being.

I’m talking about specific gene mutations that can cause or exacerbate a wide variety of menopause challenges.

These gene mutations are slow COMT genes and slow MTHFR genes.

I recently took a $59 genetic test with the company Ancestry and plugged the raw data into a free online service called Genetic Genie.

The results? I have two COMT gene mutations and one MTHFR mutation. Apparently, this is fairly common and affects at least 20% of the population.

When I first got this news I was shocked. But the more I looked into COMT and MTHFR, the more everything started making sense. It finally made sense why I’ve struggled with anxiety most of my life and why it got significantly worse when I entered menopause.

It also made sense why so many of the “healthy” things I was doing for years were actually making my symptoms worse.

It would be an understatement that this knowledge has been by far the most helpful in helping me manage my menopause symptoms. Now that I know exactly what to do, I’m no longer “shooting in the dark”. Instead, I have a practical plan that addresses my unique genes and it’s been a huge game changer.

This topic of slow COMT and MTHFR genes is so important that I’m going to dedicate several editions to it (we can’t possibly cover it all in one article!)

How do you know if you have these gene mutations? The only way to know 100% is to take a saliva DNA test. There are several out there. I chose Ancestry and it was fast, inexpensive and gave me the raw data I needed. From there, I uploaded my raw data from Ancestry into a free site called Gene Genie.

Below is a screenshot of my results from Gene Genie. The genes highlighted in red are my two slow COMT genes and one slow MTHFR gene. These are the culprits!

COMT Gene Mutations and Their Impact on Menopause

A COMT gene mutation affects the production of the COMT enzyme, which is critical for regulating cognitive function and the breakdown of certain neurotransmitters, including dopamine. Disruption in COMT enzyme activity due to a mutation can lead to imbalances in dopamine levels, particularly affecting cognitive functions associated with the prefrontal cortex of the brain. This mutation can have significant health consequences, especially for mental health and cognitive abilities, which may become more noticeable during menopause.

The Role of the Prefrontal Cortex

The COMT gene mutation is linked to increased stress reactivity by influencing the prefrontal cortex, the area of the brain responsible for managing stress, emotional responses, and cognitive functions like short-term memory, planning, and emotional regulation. Women going through menopause may experience heightened stress, anxiety, and cognitive deficits such as brain fog, partially due to the changes in hormone levels and how the COMT mutation interacts with dopamine and stress hormones like norepinephrine and epinephrine.

COMT Enzyme Activity and Menopause

COMT (catechol-O-methyltransferase) is an enzyme that helps metabolize neurotransmitters and catecholamines, including dopamine, epinephrine, and norepinephrine, which are involved in the fight-or-flight stress response. During menopause, hormonal fluctuations can exacerbate stress and cognitive challenges, especially in individuals with a COMT mutation. The COMT enzyme also plays a role in metabolizing estrogen, meaning COMT gene mutations may contribute to hormonal imbalances that are already common during menopause.

Impaired COMT enzyme function due to a gene mutation can make it difficult to break down these neurotransmitters efficiently. This can lead to a buildup of dopamine and other chemicals, contributing to heightened stress, irritability, anxiety, and even more severe mental health symptoms like depression.

Impact of COMT Mutations on Menopausal Symptoms

For women going through menopause, a COMT mutation can intensify common symptoms such as:

• Anxiety and stress responses

• Hot flashes

• Cognitive deficits (e.g., memory lapses or brain fog)

• Fatigue

• Depression

• Sleep disturbances

• Sensitivity to stress and pain

Because the COMT enzyme also metabolizes estrogens, its dysfunction may worsen estrogen imbalances during menopause, contributing to mood swings, hot flashes, and other menopausal symptoms.

Dopamine Imbalances During Menopause

Dopamine regulation is particularly important during menopause because of its role in mood, motivation, and cognitive function. COMT gene mutations can lead to either high or low dopamine levels, each with its own set of challenges:

• High dopamine: This can cause aggression, impulsivity, and anxiety, which may amplify the emotional volatility that is already common during menopause.

• Low dopamine: Symptoms like depression, low libido, lack of motivation, and mental fatigue may worsen, particularly during the menopausal transition when hormonal changes already affect mood and energy levels.

Managing COMT Mutations in Menopause

Many individuals with a COMT mutation also have MTHFR gene mutations, which can affect how the body manages methylation. Methylation is crucial for COMT function, as it helps produce the cofactors needed for neurotransmitter metabolism. Ensuring proper methylation through diet or supplements may help mitigate some of the effects of the COMT mutation.

However, caution should be taken with certain supplements that affect methylation (such as 5-MTHF, methyl B12, or SAMe), as individuals with COMT mutations often have reduced tolerance to methyl donors. Natural treatment methods and lifestyle changes, including stress management, balanced nutrition, and hormone regulation, can significantly improve outcomes for those experiencing menopausal symptoms and COMT-related issues.

When you have a slow COMT enzyme (Catechol-O-Methyltransferase), it becomes especially important to support your body in ways that enhance its ability to function optimally. COMT plays a significant role in breaking down stress hormones, neurotransmitters like dopamine and norepinephrine, and estrogens. A slow COMT, especially during menopause, can intensify common symptoms like high sensitivity to stress, mood swings, and difficulty metabolizing estrogen. However, there are effective strategies to help your body maintain balance and manage these effects during menopause.

Here's how you can support your body during menopause with slow COMT:

1. Methylation Support

During menopause, hormonal changes may exacerbate the effects of a slow COMT, making it even more important to support methylation. Since you may already have slower methylation (especially if you have the MTHFR gene variant), focusing on proper nutrients is crucial to enhance COMT’s performance.

• Incorporate methylated b vitamins like methylfolate and methylcobalamin to boost your methylation pathways, aiding in estrogen metabolism and mood balance (if you have slow COMT it may be best to take non-methylated forms of these supplements).

• Supplements like Trimethylglycine (TMG) or SAMe can act as methyl donors, further supporting the methylation process, which is essential during menopause when estrogen fluctuations can be more pronounced.

2. Magnesium is Essential

Magnesium is a key player for menopausal women with slow COMT. It not only helps with the enzyme's function but also alleviates common menopause symptoms like anxiety, irritability, and sleep disturbances by calming the nervous system.

• Include magnesium-rich foods like dark leafy greens, nuts, seeds, and avocados in your diet.

• If necessary, take magnesium supplements, such as magnesium glycinate, to support both your mood and hormonal balance.

3. Manage Stress Proactively

During menopause, stress can feel more intense due to fluctuating hormones. Slow COMT means that stress hormones like adrenaline and cortisol stick around longer, so focusing on stress management is even more critical.

• Engage in meditation, yoga, or deep breathing exercises to help lower stress levels.

• Nature walks or spending time in peaceful environments can be particularly soothing, helping reduce both stress and the physical impact of slow COMT.

4. Boost Estrogen Metabolism

As estrogen levels drop during menopause, your body’s ability to metabolize estrogen efficiently can become compromised, especially with slow COMT.

• Increase intake of cruciferous vegetables like broccoli, kale, and Brussels sprouts, which promote better estrogen metabolism.

• Consider supplements like DIM (Diindolylmethane) to further assist in breaking down estrogen and minimizing hormonal imbalances common during menopause.

5. Caffeine Sensitivity

Caffeine may exacerbate menopausal symptoms like hot flashes or mood swings for women with slow COMT, as it can lead to overstimulation and increased sensitivity.

6. Create a Low-Stress Environment

Menopause, combined with slow COMT, can make it harder to manage stress. Surrounding yourself with a peaceful, supportive environment can help mitigate the effects of prolonged stress hormones.

• Prioritize spending time in calm, serene environments, whether it’s near the ocean, in a garden, or simply a quiet room at home. This can support both your physical and mental health.

7. Nourish with Protein and Healthy Fats

A diet rich in healthy fats (like those found in avocados, olive oil, and fatty fish) and high-quality proteins is essential for stabilizing blood sugar and preventing mood swings. This is particularly beneficial for women during menopause, as fluctuating hormones can affect energy levels and mood.

8. Tailor Methylation Support if Necessary

If methylated vitamins like methylfolate or methylcobalamin feel too intense, especially with COMT’s slow breakdown of neurotransmitters, consider these alternatives:

• Use hydroxycobalamin or adenosylcobalamin (non-methylated forms of B12) and folinic acid instead of methylfolate for a gentler approach to supporting methylation.

• Start with low doses of methylated vitamins and increase gradually to allow your body to adjust.

9. Support Gut Health and Detoxification

Menopause and slow COMT can contribute to sluggish detoxification, which in turn impacts hormone balance.

• Focus on gut health by eating plenty of fiber and probiotic-rich foods to support digestion and detoxification.

• Support your liver with cruciferous vegetables and supplements like milk thistle or NAC (N-Acetyl Cysteine) to improve estrogen metabolism and help remove toxins from the body.

Recap:

• Focus on methylation support, including methylated B vitamins, or opt for gentler, non-methylated alternatives like hydroxy-b12 and folinic acid.

• Prioritize magnesium and stress management to counteract the prolonged presence of stress hormones.

• Support estrogen metabolism through diet and supplements, particularly as estrogen levels shift during menopause.

• Pay attention to caffeine and neurotransmitter sensitivity and adjust your lifestyle to maintain balance.

By understanding how your slow COMT functions and embracing these strategies during menopause, you can better manage the hormonal and emotional changes that arise, creating balance and harmony within your body.

Final Thoughts…

Yes, this is a lot of information and don’t expect to digest everything at once. Genetics is a complicated study and I’m still learning every day. But it’s worth the effort. As I mentioned at the beginning of this article, having genetic mutations like COMT and MTHFR are so common and impact our health so dramatically that they simply can’t be ignored. The good news is once we know what’s going on with our genes, then we can implement a practical, science-based strategy to get the relief we’re all seeking.

Stay tuned for more information next week as we do a deeper dive into specific natural supplements, dietary changes and other protocols you can follow that work in harmony with your unique genetic makeup so you can start feeling like you again!

Take care,

Sophia