liver health

PEMT

Genetic Factors of Fatty Liver (PEMT)

Written by Aleksa Ristic, MS (Pharmacy) on September 9th, 2019

Your liver depends on PEMT to get rid of excess fat and stay healthy. One variant suppresses the PEMT gene and correlates with fatty liver. Read on to learn more about the genetics of fatty liver and how it’s related to the methylation cycle.

The PEMT Gene

PEMT encodes an enzyme (Phosphatidylethanolamine N-methyltransferase) which produces phosphatidylcholine (PC) in the liver. It converts phosphatidylethanolamine (PE) into PC by three-step methylation, with the help of S-adenosylmethionine (SAM-e) [R].

This pathway is the only source of choline in the absence of food sources. It has played a critical evolutionary role by supplying choline and PC during periods of starvation [R, R].

PEMT is mainly expressed in the liver and accounts for 30% of liver PC production. Choline and PC are essential for [R, R, R]:

Cell membranes
Signaling
Fat transport and metabolism
Brain health

PEMT produces phosphatidylcholine (PC) in the liver via methylation. It supplies choline and PC in the absence of food sources of choline, thus maintaining cell structure, fat metabolism, and brain health.

Choline, PEMT, and Fatty Liver

Phosphatidylcholine (PC) helps break down fats in the liver and send them to other parts of the body. A lack of PC, due to choline deficiency or low PEMT activity, can cause fat to accumulate in the liver [R, R].

Mice without PEMT quickly develop fatty liver when fed a high-fat diet, indicating a vital role of this enzyme in liver health [R].

In a meta-analysis of six clinical trials with over 3,500 participants, one PEMT variant was associated with non-alcoholic fatty liver disease (NAFLD). In these trials, people with a “T” allele on rs7946 had 55% higher rates of NAFLD compared to those without [R].

The connection is particularly strong in people of East Asian ancestry. Luckily, the “T” allele is much less common in this population [R].

In a small study of European descendants, the “T” allele at rs7946 was more common among NAFLD patients, but another trial failed to confirm this. The authors hypothesized that the PEMT variant could worsen the effects of risk factors, such as overeating and a sedentary lifestyle [R, R].

The “T” allele on rs7946 may be associated with higher rates of fatty liver. This variant is significant among people from East Asia, and it may worsen the effects of overeating and sedentary lifestyle.

Should You Worry About Fatty Liver?

Given that NAFLD affects 20-30% of people in the Western world, the short answer is “yes.” Obesity, diabetes, and other metabolic disorders increase the risk of this condition [R].

You may not notice any symptoms in the early stages, so it’s essential to check your liver enzymes and do an ultrasound exam if you or your doctor suspect any changes.

PEMT Variants and Fatty Liver — How It Works

Phosphatidylcholine (PC) helps produce VLDL, which exports fat from the liver into the bloodstream. Additionally, PC suppresses the formation of triglycerides in the liver and accelerates fat burning [R, R, R, R].

Carriers of the “T” allele at rs7946 may have reduced PEMT function. This would imply lower PC production and quicker liver fat buildup. In one lab test, the “TT” genotype resulted in a 30% loss of PEMT function. This mechanism has yet to be proven in better-designed trials [R].

The Role of Estrogen

Men and postmenopausal women have higher rates of NAFLD compared with younger women. That’s likely because estrogen stimulates PEMT expression and activity, supplying adequate amounts of PC [R, R].

In those who carry the rs7946-T variant, estrogen may make up for this effect and maintain normal PEMT activity.

The rs7946-T variant reduces PEMT function, which may cause lower PC levels and increased liver fat buildup. Estrogen can counteract this effect by boosting PEMT expression and activity.

Your PEMT Results for Fatty Liver

Primary SNP: PEMT rs7946

‘C’ = Normal PEMT activity, doesn’t correlate with fatty liver
‘T’ = Reduced PEMT activity, may correlate with fatty liver

Population Frequency:

50% of European descendants have the “TT” genotype
4% of East-Asian descendants have the “TT” genotype

SNP Table

variant	genotype	frequency	risk allele
rs7946

Recommendations

Lifestyle

Chronic excessive alcohol consumption can wreak havoc on your liver. It causes fatty liver, inflammation, and scarring [R, R].

Suppressed PEMT may be one of the reasons drinking causes liver fat buildup. Alcohol also reduces PEMT activity indirectly by lowering the levels of S-adenosylmethionine [R].

Try to limit alcohol consumption or avoid it completely.

Diet

If low PEMT activity impairs phosphatidylcholine (PC) and choline production, getting enough choline from food should compensate for this effect. The liver will then produce PC via the CDP-choline pathway, which depends on adequate choline supply [R].

Enzymes in the CDP-choline pathway were 60% more active in PEMT-deficient mice. Choline supplementation improved their liver function and prevented fat buildup [R, R, R].

Adequate choline intake is associated with lower rates of fatty liver [R, R, R, R].

Adult men need 550 mg of choline daily, while women need 425 mg. The best food sources include [R, R]:

Beef liver
Eggs
Chicken
Codfish
Shiitake mushrooms

If PEMT can’t produce enough PC, it’s essential to get enough choline from food. The best sources include beef liver, eggs, chicken, codfish, and shiitake mushrooms.

Supplements

Choline

Different supplement forms of choline can increase dietary intake and compensate for low PEMT activity. These include:

Plant-Derived Estrogens

Certain plant-derived substances mildly stimulate estrogen receptors; they may compensate for the lack of PEMT-boosting estrogen, but this mechanism requires further investigation [R, R].

Resveratrol is a potent antioxidant from grape skin, which can stimulate estrogen receptors and support the liver [R, R, R].

In a small clinical trial, 6-month supplementation with resveratrol significantly reduced liver fat [R].

EGCG from green tea may also support estrogen functions in the liver (via estrogen receptor alpha) and thus increase PEMT activity [R, R].

Different animal trials have found EGCG beneficial for fatty liver. Green tea extract reduced liver enzymes in 80 NAFLD patients [R, R].

These supplements are more popular among postmenopausal women, but anyone may find them useful. They are safe and don’t cause hormonal imbalance when taken at recommended doses [R, R].

Some plant compounds—such as resveratrol and EGCG—may compensate for low estrogen, increase PEMT activity, and improve liver health.

SAM-e

When PEMT makes phosphatidylcholine, it takes methyl groups from S-adenosylmethionine or SAM-e. Thus, more SAM-e = active PEMT [R, R].

SAM-e boosts glutathione and, according to different clinical trials, may help with chronic liver disease [R].

Keep in mind that the above supplements aren’t approved by the FDA to prevent or treat any medical condition.

Aleksa Ristic

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Genetic Factors of Fatty Liver (PEMT)

The PEMT Gene

Choline, PEMT, and Fatty Liver

Should You Worry About Fatty Liver?

PEMT Variants and Fatty Liver — How It Works

The Role of Estrogen

Your PEMT Results for Fatty Liver

SNP Table

Recommendations

Lifestyle

Diet

Supplements

Choline

Plant-Derived Estrogens

SAM-e

Disclaimer

More liver health blogs

Content

Unlock Personalized Results And So Much More!

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