The PEMT Gene: Key to Fatty Liver, Muscle Weakness and Brain Fog

A science-based look at an often underestimated genetic factor

Introduction

At DNA Care, we regularly see clients whose diverse symptoms trace back, at least in part, to a genetic variant in the PEMT gene. Many have been on a long medical journey, undergoing numerous tests and assessments, but without a clear explanation. The signs are varied, yet often form a recognizable pattern:

Brain fog and cognitive slowing (subjective cognitive complaints)
Hormonal imbalance, such as oestrogen dominance or disruption of steroid hormone metabolism
Fatty liver (NAFLD / MAFLD) or abnormal liver function tests
Memory and concentration problems
Muscle weakness or muscle pain
Digestive issues (including gallbladder problems)
Elevated homocysteine (biochemical marker and cardiovascular risk factor)
Persistent fatigue and low energy levels

💡 The PEMT gene influences fundamental processes such as cell membrane integrity, liver detoxification, methylation, and hormonal balance.

What is the PEMT Gene and Why is it Important?

The PEMT gene (Phosphatidylethanolamine N-methyltransferase) encodes the PEMT enzyme, which produces phosphatidylcholine in the liver from phosphatidylethanolamine.

Phosphatidylcholine is vital for:
• Formation and maintenance of flexible cell membranes – the primary role of phosphatidylcholine, vital for the structural integrity and intercellular communication of all cells.
• Transport of fats and cholesterol from the liver (VLDL export) – prevents hepatic fat accumulation and supports a healthy lipid profile.
• Production and secretion of bile for fat digestion – essential for absorbing dietary fats and fat-soluble vitamins, and for maintaining optimal gut health.
• Methylation processes (conversion of homocysteine to methionine) – important for cardiovascular health and the regulation of gene expression through epigenetic mechanisms.
• Regulation of oestrogen balance – contributes to hormonal stability, partly via optimal phosphatidylcholine synthesis.

The human body comprises more than 37 trillion cells, with hundreds of billions replaced daily. Each cell is enclosed by a membrane that safeguards its contents and enables precise communication. Phosphatidylcholine is an integral component of these membranes, ensuring that nutrients can enter the cell efficiently while waste products are effectively removed.

💡 A well-functioning PEMT gene supports healthy cell membranes, a vital liver, and stable hormonal balance.

When the PEMT Gene Functions Suboptimally

When the PEMT gene is not functioning optimally, the production of phosphatidylcholine can decrease. This increases the risk of choline deficiency and can have consequences for multiple systems in the body. The impact often becomes evident when several symptoms occur together, such as:
• Fatty liver (NAFLD / MAFLD) – hallmark risk of reduced PEMT activity.
• Brain fog and reduced cognitive function (subjective cognitive complaints) – often linked to choline deficiency.
• Hormonal imbalance, especially estrogen dominance or steroid hormone disruption – linked to PEMT’s role in hormonal regulation.
• Gallbladder problems or gallstones – related to impaired bile production and flow.
• Muscle weakness or muscle pain – possible consequence of impaired phospholipid metabolism.
• Elevated homocysteine (biochemical marker and cardiovascular risk factor) – linked to methylation cycle involvement.
• Reduced liver detoxification capacity – secondary to impaired phosphatidylcholine production.
• Chronic fatigue and physical exhaustion – common but non-specific downstream effect.

💡 A shortage of phosphatidylcholine can lead to structural damage to cell membranes, impaired detoxification, and neurological symptoms such as brain fog.

Causes of Reduced PEMT Activity

The function of the PEMT gene can be influenced by both genetic and epigenetic factors.
Key causes include (in order of relevance):

• Genetic predisposition – certain SNPs lower enzyme activity
• Low estrogen status – estrogen stimulates PEMT via estrogen response elements in the gene promoter; low levels (e.g., post-menopause) reduce activity
• Low-choline diet – especially problematic during increased needs (pregnancy, breastfeeding) or poor absorption
• Deficiency in methylfolate or other methyl donors – such as folate, vitamin B12, betaine
• Fatty liver or liver inflammation – can lower PEMT activity
• Epigenetic factors – stress, toxic exposure, chronic inflammation

💡 Even with a genetic predisposition, PEMT activity can be influenced through diet, hormones, liver health, and lifestyle.

A Case from Our Clinic

A 39-year-old woman came to DNA Care with chronic fatigue, brain fog, hormonal symptoms, and recently diagnosed fatty liver (NAFLD). A PEMT gene test revealed a variant in the PEMT gene, combined with elevated homocysteine and low oestrogen levels. Her dietary analysis showed consistently low choline intake.

After six months of targeted support – including choline-rich foods (such as eggs and liver), methylation support, hormone balancing interventions, and liver repair – her liver enzymes had normalised, homocysteine levels had decreased, and symptoms had significantly improved. She also reported complete resolution of brain fog and improved concentration.

💡 Addressing genetic vulnerabilities can lead to measurable improvements in liver function, hormonal balance, and brain health.

From Genetic Insight to Epigenetic Potential

At DNA Care, we see genetics as a starting point, not an endpoint. The PEMT gene responds to:

• Adequate choline and dietary methyl donors – including folate, vitamin B12, and betaine
• Hormonal balance, particularly optimal oestrogen status
• Liver function and detoxification efficiency
• Healthy microbiome composition and diversity

By optimizing these factors, PEMT activity can be increased, even in the presence of genetic variants.

💡 Your genetic predisposition is not your destiny — with the right signals, PEMT gene function can improve.

The Role of the Microbiome

The microbiome plays a dual role in choline metabolism. Certain beneficial bacterial strains can liberate choline from dietary sources, making it available for absorption and use in phosphatidylcholine synthesis. However, other microbial species can degrade choline into trimethylamine (TMA), which is subsequently oxidised in the liver to trimethylamine N-oxide (TMAO). Elevated TMAO levels have been associated in research with increased cardiovascular risk. An imbalanced or dysbiotic microbiome can therefore contribute both to functional choline deficiency and to the generation of potentially harmful metabolites, highlighting the importance of maintaining microbial diversity and balance.

💡 Your microbiome can be your ally or your adversary in choline metabolism.

Recent Scientific Insights

In recent years, understanding of the PEMT gene has deepened through genetic, metabolic, and endocrinological research. Key findings include:

• PEMT and fatty liver – Polymorphisms in the PEMT gene increase the risk of non-alcoholic fatty liver disease (NAFLD, now often referred to as MAFLD), particularly in the context of low choline intake. Phosphatidylcholine is essential for packaging triglycerides into VLDL particles; deficiency leads to fat accumulation in hepatocytes and progressive liver dysfunction.

• Estrogen and PEMT – The PEMT gene contains estrogen response elements in its promoter region, enabling estrogen to stimulate gene expression. This helps explain why premenopausal women are often better protected against choline-deficiency-related fatty liver, while postmenopausal women are more vulnerable.

• Choline in pregnancy – Choline requirements increase substantially during pregnancy, in part for the development of the foetal brain and spinal cord. Women with PEMT variants are at greater risk of deficiency during this period, which may contribute to growth restriction and neurocognitive developmental problems in the child.

• Methylation and cardiovascular risk – Phosphatidylcholine is integral to the methylation cycle. Reduced PEMT activity can lead to elevated homocysteine, a biochemical marker associated with higher cardiovascular risk, endothelial dysfunction, and oxidative stress.

💡 These findings confirm that the PEMT gene plays a central role at the intersection of nutrition, hormonal regulation, liver function, and cardiovascular health.

Functional Medicine Approach at DNA Care

Our approach to PEMT gene-related concerns involves:

• Comprehensive DNA analysis – assessing PEMT, methylation, and liver-related genes
• Targeted hormonal optimization – supporting healthy estrogen status where appropriate
• Advanced laboratory testing – including homocysteine, liver function markers, and detailed hormone profiling
• Liver and microbiome restoration – personalized strategies to improve function and balance
• Tailored nutritional guidance – focusing on choline-rich foods and supplementation when indicated

💡 By integrating genetics, nutrition, hormones, and liver health, we create a tailored plan for optimal recovery.

Top 5 Signs of Reduced PEMT Activity

• Brain fog and cognitive complaints (subjective cognitive complaints)
• Hormonal imbalance (oestrogen dominance or steroid hormone disruption)
• Fatty liver (NAFLD/MAFLD) or abnormal liver enzymes
• Muscle weakness or muscle pain
• Elevated homocysteine (biochemical marker and cardiovascular risk factor)

💡 Recognizing these signs can lead to targeted diagnostics and intervention.

Your health is the result of many interconnected systems – biological, emotional, and mental. At DNA Care, we translate genetic and epigenetic insights into concrete, measurable steps for recovery and prevention. With nearly two decades of expertise in genetics, epigenetics, and Functional Medicine, we combine scientific precision with personalized care.