Methylation Part 2: Take a minute to learn about choline and why we can't live or be happy without it

In which we examine the role this nutrient plays in methylation, cholesterol, and fatty liver disease.

Introduction: For our US readers it’s election eve—a time far more wracked by fear and anxiety than Halloween which was just a few days ago. However, I have some excellent news to relieve your jitters! After a much lengthier than intended hiatus the Orthomolecular Guy newsletter is back! Even better, I have never, and will never, discuss politics here so you can take a much needed break from the noise, madness, chaos, and constant anxiety of this election cycle. Instead, take a few minutes to learn about the fascinating nutrient known as choline. It’s more commonly encountered in the wild as phosphatidylcholine, also called lecithin, which you might have heard of before. But for the rest of this newletter for the sake of ease of understanding I’m going to just use the term choline. From my observation, it plays such a critical role in human health yet is very underrated and underrepresented in popular nutrition writing. So without further ado let’s dive in…

Part one: Review of methylation and introduction to choline and lecithin

In my first post on methylation and creatine, I explained that the synthesis of creatine requires typically 40% of the body’s entire output of SAMe, (s-adenosyl-L-methionine) which is the end result of the methylation cycle. SAMe is generated by the methylation of the amino acid methionine (by way of homocysteine) with methyl groups donated by the enzyme MTHFR, which requires the micronutrients folate and vitamin b-12 to function. We discussed how taking creatine was a safe and effective way to reduce the burden on the methylation system and could be very helpful for people with MTFHR SNP’s who do not methylate as efficiently. But did you know that there is another essential chemical required by almost every cell in the body that also uses as much as 40% of a person’s methylation capacity? Yep, you guessed it, I’m talking about choline which is commonly found in many animal products and is often added to processed foods as an emulsifier of fat. (which is a huge hint as to why it helps the liver) If you have ever eaten an egg, you have consumed it. If you have ever eaten liver, or any product made from soybeans, such as edamame, tofu, or sunflower seeds, you have eaten it. The mayonnaise in your sandwich and most products with chocolate would not be smooth and silky without it.

Part 2, The body’s many uses for and desperate need for choline

In human physiology, it is:

1. Used by almost every cell in the body where it is part of the cell wall

2. Used by the brain and nervous system as a neurotransmitter

3. Used to transport cholesterol out of the liver

4. Used as a methyl donor as part of the BHMT enzyme, which like MTHFR, can satisfy the body’s needs for methylation

If those functions sound important, it is because they are! Without this nutrient, we would not have the structural integrity of our cells and would just collapse into a pile of mush. All mammals and plants use choline for this purpose- it is completely essential to all higher forms of life. Humans can synthesize phosphatidylcholine, but most people can not make enough to satisfy the demands of the body, and it is mandatory to get it from diet. (6)

However, the massive NHANES study in 2014 found that most Americans are getting some, but not enough choline in their diet. This is especially true for vegetarians and vegans since most of the high dietary sources of choline are liver, meats, and eggs. (5) I do want to encourage all plant-based eaters to read on, however, as I have some excellent news for them about choline intake in the recommendations section.

About half of the phosphatidylcholine we consume is sent to the liver, where it goes through a process called phosphorylation (phosphorus groups added) so it can be used in cell wall synthesis. The other half is absorbed whole by the lymphatic system [side note, this is why liposomal vitamin C which is made with lecithin, is absorbed so powerfully and doesn’t cause gastric upset] and then distributed directly to the blood supply where it is supplied to the brain, placenta, and other organs that need it. (4)

Part 3 The intertwined role of lecithin in methylation and fatty liver disease

Similar to how supplementing with creatine can reduce the demand on the methylation system, so will consuming adequate choline. The reason for this is that like creatine, humans can manufacture choline, a process called de novo synthesis, but it is very taxing on the methylation system, requiring as much 30% to 40% of the body’s SAMe pool. Let’s examine this graphic, which shows the Choline/Betaine cycle and its role in methylation. At the bottom of the graphic, we see the molecule phosphatidylethanolamine being acted on by the enzyme PEMT. We see that three molecules of SAMe (here called SAM) are used to form phosphatidylcholine. This is the process of de novo choline synthesis. To make it a little clearer, it takes 3 methyl groups to form one molecule of phosphatidylcholine of which each cell in our body has many thousands of these molecules. (3)

The liver depends on the MTHFR enzyme to convert homocysteine to methionine to SAMe for these methyl groups. So you can see how people with compound heterozygous MTHFR or homozygous c677t get into trouble as they have about 60-70% less methyl groups than people who don't have these SNP's. Further compounding potential problems, it is also quite common for the PEMT enzyme to have SNPs. This enzyme makes choline and SNPs on it reduce its function similar to how SNPs of the MTHFR enzyme reduce its function. If you have a SNP on the PEMT enzyme, that will translate to a reduced rate of choline synthesis. This, in turn, will lead to fatty liver disease, especially if one’s diet is choline-poor. The reason for this is due to the ability of lecithin to emulsify fat. It does so in your chocolate bar, and it does so in your liver. It is as simple as this-without proper amounts of lecithin, fat cannot leave the liver and must be stored there. Over time, this leads to fatty liver disease, which can lead to the much worse liver diseases steatohepatitis and liver cancer, especially if the patient already has metabolic syndrome and high cholesterol. PEMT knockout mice (meaning mice that have had their PEMT gene removed and can’t manufacture lecithin) end up with fatty liver disease in 100% of cases. What is fascinating is that they are able to reverse the fatty liver by simply feeding them a high lecithin diet. Recent studies such as ones with such stimulating titles as Hepatic PEMT Expression Decreases with Increasing NAFLD Severity (4) have proven that the same effect is seen in humans with this genetic variation. NAFLD stands for non-alcoholic fatty liver disease and is the main source of liver disease in modern times affecting over 40 million Americans. This study shows us that those with SNPs on their PEMT gene cannot manufacture enough choline to keep up with demand, and increased risk of fatty liver disease is the result. (4)

So we can see how those with MTHFR, are MORE likely to have fatty liver disease due to the impairment in methylation leading to insufficient synthesis of choline, especially if they also have the PEMT SNP. However, there is one more facet of choline and methylation we need to discuss. And that is the role of choline as a methyl donor. Above I mentioned that it takes 3 methyl groups to make one choline molecule and that simply consuming enough of it takes a lot of strain off the methylation system. But there is another benefit in that dietary choline can directly contribute methyl groups to the methylation cycle. I invite you to look at the diagram below and let your eyes follow the arrows from the green box that says dietary choline over to the left. It shows choline being acted on by an enzyme called choline oxidase, which turns it into a substance called betaine (pronounced Beet-a-een for some reason) where you can see it flows into the methionine to SAMe cycle where it donates its methyl groups. It does so using an enzyme called BHMT that functions in a parallel manner to MTFHR. Methyl groups are so important that our bodies have evolved not one, but TWO enzyme systems to make sure we have enough of them for our needs. MTFHR is one, and BHMT is the other. Folate and b12 are needed for MTFHR to work, whereas betaine is needed for BHMT to work, and this can come from dietary choline as I outlined above. This why along with taking creatine, I recommend dietary choline to support MTFHR (4)

Part 4. Some remarks on choline for high cholesterol and brain health.

Look again at the graphic above, and this time let your eyes go to the right and see the other roles of dietary choline. You can see that it is acted on by an enzyme called ChAT (choline acetyltransferase) which adds an acetyl group to choline and make it into the vital neurotransmitter acetylcholine. The physiology and uses for acetylcholine are too extensive to go into in this article, but they are quite numerous and complex, and it is enough to say for now that acetylcholine is essential for memory, cognition, and mood. It is also needed for neurological functions like blood pressure control, posture, intestinal peristalsis (what makes you poop), and the other functions of the autonomic nervous system. This is called the cholinergic system and it is well known to science and many medicines target acetylcholine as a treatment. Its cruciality to brain health can’t be overstated.

Lastly, let’s briefly examine the role of choline in cholesterol metabolism. Since, per the CDC, over 100 million Americans have high cholesterol, I thought this might be most relevant to many of my readers and saved the best for last. Cholesterol is made in the liver as part of healthy fat metabolism. It needs to exit the liver and it does so as VLDL cholesterol (Very low-density lipoprotein). For this to be achieved choline must be present in enough quantities, or the VLDL will not get out. This leads to both impaired cholesterol metabolism and fatty liver disease. Choline deficiency is not the only cause of fatty liver disease, which is usually seen in patients with metabolic syndrome, or type 2 diabetes, or obesity. Diseases like high cholesterol and fatty liver are complex and multifactorial, but the simple fact is that choline deficiency alone can cause fatty liver and correcting this deficiency can cure it (4). Several studies have found a direct correlation to reversing fatty liver disease with soy lecithin supplementation, as well as lowering high cholesterol. One study I looked at from 2010 had an astonishing 42% drop in total cholesterol levels in those who had just 500mg of soy lecithin per day for a two month period. (7) Another study I looked at found that 2400 milligrams of lecithin for 4 weeks produced a 20-point drop in cholesterol which is highly significant. (8) Unfortunately these studies were not very large and not enough research has been done in humans to date for your doctor to say you should consume/supplement choline for your fatty liver or high cholesterol. Nevertheless, the idea has solid mainstream acceptance in the nutritional and medical community and should be considered strongly.

Who should be concerned about choline intake:

1. People with high cholesterol absolutely should consider increasing their choline intake.

2. People with fatty liver disease

3. Vegetarians and Vegans and Whole Food Plant Based dieters

4. Those with MTHTF and/or PEMT SNP’s

5. Those who are pregnant or lactating.

6. Those with metabolic syndrome or type two diabetes

Part 5 Summary and discussion on diet/supplements

I think that I have made a pretty compelling case for the importance of an adequate choline intake. As I mentioned above, very few people get enough. So let’s take a look at how much we are supposed to be eating and discuss how to get there.

(note, please discuss with your doctor any dietary changes or supplements, especially if pregnant or lactating)

Per the NIH nutritional guidelines, the recommended choline intakes are:

• 425 mg per day for women,

• 500 mg per day for men.

• 450 mg per day in pregnancy and

• 550 mg per day during lactation.

• 125 mg/day125 mg/day birth to 6 months

• 150 mg/day150 mg/day 7-12 months

• 200 mg/day200 mg/day 1-3 years of age

• 250 mg/day250 mg/day 4-8 years of age

• 375 mg/day375 mg/day 9-13 years of age

Here is a simple list of the top ten choline-containing foods and how much they contain per 100 grams of that food. As you can see eggs easily top the list.

Food Choline Content per 100 grams One egg 147 mg, Beef liver 359mg, Chicken liver 290mg, Salmon 187mg, Beef top round 3 ounces 117 mg, Soybeans 107mg, Chicken breast 3 ounces 72 mg, Shiitake mushrooms 45 mg , Potatoes 57mg, Brussels sprouts 32mg, Broccoli 31mg, Cauliflower 30mg, Almonds 26 mg

Clearly, for omnivores it would be quite possible to get 450 mg of choline per day from having 3 eggs, and then make up the rest by mixing and matching the other foods above. However, it’s possible you might not want to have 3 eggs per day or worry about the cholesterol in the eggs. One study I found shed some interesting light on this: it compared people who had 3 eggs per day vs taking 450 of choline bitartrate per day and it found that while cholesterol went up slightly in the egg group, the LDL/HDL ratio didn’t change at all, probably due to the high amount of choline. (9) So for a person with good cholesterol, having eggs every day can get you quite close to the recommended intake, especially if you pair it with other foods from the list. Liver is the next highest source. I know liver isn’t popular, but it’s also the highest source of vitamin A, copper, iron, all the b vitamins, and more. There is no more nutrient-dense food than liver and I recommend it highly.

For vegans and omnivores who don’t want to eat meats in such high doses, probably the best way to get choline is from soy lecithin granules. Soy has had a lot of bad press over the years, but in truth, there are many decades of research behind the health benefits of soy protein and soy fat, which is called lecithin and I recommend soy products wholeheartedly except for perhaps drinking soy milk in large quantities. I recommend granules because they can be added to a smoothy or yoghurt quite easily and you won’t even taste them. Liquid sunflower lecithin is another good choice, but it is very hard to get down! The rule of thumb with lecithin is that is about 20% to 25% phosphatidylcholine, which in turn is 13% pure choline. So if you took one tablespoon of lecithin granuals, you will get about 1500-2000 mg of phosphatidylcholine, and about 175-220 mg of choline. I for one used to take two tablespoons of lecithin per day in my daily smoothy for many years and I figured I got 400 mg per day or so, and rest of my daily recommended intake came from the meat in my keto diet that I was doing at the time.

Of course there are other supplements one can readily find at many retailers such as choline bitartrate, CDP choline, or Alpha GPC. The latter two are for nootropic use (brain performance enhancers) and I’m not looking to discuss those today. Choline bitartrate is often not well tolerated in the gut of many users. I really do think the best way to get choline is from diet, and lecithin is the only supplemental form I like to recommend because it is a food based supplement. My reasoning for this is that there is some controversy around choline supplementation and increased cardiovascular risk from a metabolite of choline made by gut bacteria called TMAO. Per the Linus Pauling nutritional center at the University of Oregon this is more likely to arise from supplementation rather than from a diet high in choline contained foods or a lecithin supplement. (6)

Finally, I don’t recommend shooting for MORE than the recommended intake either, primarily due to the potential risk from TMAO. Rather I think you will reap all the benefits of this life-giving nutrient and minimize all the risks if you stay in the recommended ranges I posted above.

Parting words:

I hope you enjoyed this welcome distraction from stressing out about the election. However you vote tomorrow, I send all of you my very best wishes for ever increasing mental, physical, and spiritual health.

As always thank you for reading, and sharing this newsletter with your friends and family, and supporting my mission to provide life-changing information to the countless millions of people who would like to enjoy greater mental and physical wellness. 

All the best on your journey to better mental and physical health! 

Disclaimer: I am not a medical doctor.  The information in this article does not constitute medical advice and is not intended to diagnose or treat a disease. Readers should speak with their personal medical professional before acting on any of the information discussed

1. American Liver Foundation https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-fatty-liver-disease-nafld/ accessed 8-22-2024

2. Zeisel, S. H. (2017). Choline, other methyl-donors and epigenetics. Nutrients, 9(5), 445. https://doi.org/10.3390/nu9050445

3. Chen, X., Qiu, W., Ma, X., Ren, L., Feng, M., Hu, S., Xue, C., & Chen, R. (2024). Roles and mechanisms of choline metabolism in nonalcoholic fatty liver disease and cancers. Frontiers in Bioscience (Landmark Edition), 29(5), 182. https://doi.org/10.31083/j.fbl2905182

4. Piras, I. S., Raju, A., Don, J., Schork, N. J., Gerhard, G. S., & DiStefano, J. K. (2022). Hepatic PEMT expression decreases with increasing NAFLD severity. International Journal of Molecular Sciences, 23(16), 9296. https://doi.org/10.3390/ijms23169296

5. Office of Dietary Supplements, National Institutes of Health. (n.d.). Choline. Retrieved November 4, 2024, from https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/

6. Linus Pauling Institute, Oregon State University. (n.d.). Choline. Retrieved November 4, 2024, from https://lpi.oregonstate.edu/mic/other-nutrients/choline#liver-diseases-prevention

7. Mourad, A. M., Pincinato, E. C., Mazzola, P. G., Sabha, M., & Moriel, P. (2009). Influence of soy lecithin administration on hypercholesterolemia. Cholesterol, 2010, 824813. https://doi.org/10.1155/2010/824813

8. Jan, M., Thondre, P. S., El-Chab, A., & Lightowler, H. J. (2017). The effect of dietary phosphatidylcholine supplementation on lipid profile in mild hyperlipidaemic individuals. Proceedings of the Nutrition Society. Published online by Cambridge University Press. https://doi.org/10.1017/S0029665117002008

9. Lemos, B. S., Medina-Vera, I., Blesso, C. N., & Fernandez, M. L. (2018). Intake of 3 eggs per day when compared to a choline bitartrate supplement, downregulates cholesterol synthesis without changing the LDL/HDL ratio. Nutrients, 10(2), 258. https://doi.org/10.3390/nu10020258