33. Over-Methylation Explained: COMT, Estrogen, Mood & Inflammation

In this episode of the Histamine Well Podcast, Joanne Kennedy explains why over-methylation is becoming increasingly common, especially among women, and how it’s closely linked to COMT enzyme activity, estrogen dominance, mood disorders, and inflammation.

This episode breaks down the biochemistry of methylation in a clear, practical way—exploring how estrogen affects COMT, why some people react badly to methylated B vitamins, and how over-methylation can drive symptoms such as anxiety, irritability, insomnia, nervous system overload, and chronic inflammation.

Joanne also introduces the Mood Sense test as a real-time tool for assessing methylation status, helping practitioners and individuals move away from guesswork and toward personalized, symptom-aware support. With insights inspired by James Bradshaw, this episode is essential listening for anyone navigating estrogen-related symptoms, mood instability, or complex supplement reactions.

What you’ll learn in this episode:

• Why over-methylation is becoming more common, especially in women
• How COMT enzyme activity influences mood, stress tolerance, and neurotransmitter
• The connection between estrogen dominance and over-methylation
• Common emotional and inflammatory symptoms linked to over-methylation
• Why methylated supplements can worsen symptoms for some people
• How the Mood Sense test can help assess methylation status in real time
• Key considerations for supporting estrogen balance and calming the nervous system

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