Phosphatidylcholine and Menopause: A key Nutrient for improving mental health

Fact-checked – 4 min read

Overview
During menopause, falling estrogen levels can reduce the activity of the enzyme phosphatidylethanolamine N-methyltransferase (PEMT), often contributing to brain fog, memory issues, and reduced cognitive sharpness(1). But what exactly is PEMT, and how does estrogen influence its function and impact neurological health during menopause?

PEMT: Function and relevance to health
The PEMT gene encodes an enzyme essential for converting phosphatidylethanolamine (PE) into phosphatidylcholine (PC). This process, particularly active in the liver, serves as an alternative to the CDP-choline pathway for PC synthesis, known as the ‘Kennedy pathway’ (Fig 1). PS: no relation to former president Kennedy! Phosphatidylcholine is integral to cell membrane structure and function and is particularly important for brain health, as it serves as a choline source, a precursor to acetylcholine, the neurotransmitter critical for memory and learning. Ensuring sufficient choline, could therefore reduce the risks of neurodegenration in post-mennopausal women (1).

Estrogen and PEMT regulation
Estrogen enhances PEMT activity by binding to its gene promoter and thus encourages PC synthesis (2). Premenopausal women, with higher estrogen, maintain PC levels more efficiently. After menopause, this estrogen-driven pathway becomes less active, reducing PC and choline availability and potentially impairing acetylcholine synthesis, linking to the cognitive symptoms often reported during post-menopause. 

Ergo, I posit that hormone replacement therapy (HRT) may reduce the need for supplemental choline in postmenopausal women, effectively restoring a woman’s ability to produce adequate choline internally, similar to premenopausal levels (3). Therefore, external choline supplementation may become less necessary when estrogen levels are restored through HRT, whilst those not on HRT may benefit by increasing choline rich foods (1). Table 1 below provides an overview of animal-based choline rich sources and approx content per serving (4). Table 2 depicts plant-based choline sources per 100g, but they contain far less amounts compared to animal sources.

Recommended daily intakes
Pregnant/breastfeeding: 450–550 mg/day
Adult women: 425 mg/day
Adult men: 550 mg/day

What does the research say?
Supplementing with phosphatidylcholine can help support membrane integrity and brain function by replenishing choline stores. A study by Fischer and collegues published in 2010 (5), showed that estrogen therapy in postmenopausal women improved choline metabolism, reducing the need for external choline to premenopausal levels. Therefore as suggested earlier, using hormone replacement therapy (HRT) may reduce the need for supplemental choline in postmenopausal women, effectively restoring a woman’s ability to produce adequate choline internally similar to premenopausal levels, reducing the need for oral choline supplementation. Conversely, choline requirements may increase without HRT

Dosing & Conclusion
As estrogen declines with age, so does PEMT activity. Supporting this pathway through PC supplementation may help manage menopausal cognitive symptoms and maintain brain health in postmenopausal women. Typical dosing is approx 1.2-4 grams per day, adjusted based on individual responses, symptoms, and choline status. However, like with any supplement, exceeding physiological needs for counterbalance and increase the requirements of other nutrients, so it’s important to have a broader understanding of these interactions, especially with any prescribed medications. Therefore, I strongly recommend you consider at least a single consultation with me so that I can help evaluate your particular case history and make more meaningful and personalised recommendations for you.

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