Methylation Cycle and Phosphatidyl Choline
Methylation is an important topic in functional medicine and increasingly in conventional medicine as well. Those who’ve experienced frequent miscarriages, cardiovascular disease or chronic fatigue may have had homocysteine levels or their MTHFR gene tested. They may have been told that there is a methylation issue, and they need more B vitamins.
This is good advice to an extent, but there is more to the methylation story. Most of the focus on improving methylation is on making more methyl groups. However, we can also decrease the body’s need for methyl groups to improve methylation. This takes the pressure off a genetic mutation or other factors that may be slowing down the MTHFR enzyme.
It’s like taking the focus off working harder and harder to make more money and instead managing the money you do have more efficiently to meet all your needs with less stress.
If all of this is new to you, don’t worry, I’ll walk you through all these terms and concepts, so you have a good understanding of the methylation cycle and how to best support this incredibly important process in your body.
Keep reading to learn more about:
- Methylation and the methylation cycle, including main inputs and key products
- Factors that slow down methylation pathways
- Phosphatidyl choline and how it provides methylation support
- Key action items to optimize methylation
Let’s jump right in!
What Is Methylation and The Methylation Cycle? What Slows It Down?
On one hand, methylation is a simple biochemical process that adds a methyl group to another molecule. A methyl group is one carbon atom attached to three hydrogen atoms. Adding a methyl group (or removing one) is a key step in many body processes including genetic expression, detoxification, growth, neurotransmitter production and more. This simple molecular handoff is critical for life and is happening every second in your body.
On the other hand, methylation can be quite complex, and it takes a lot of factors for the process to run smoothly, and optimally.
The methylation cycle, as pictured below, is a biochemical cycle that turns the amino acid methionine (that you get from food) into another amino acid homocysteine, and back again. Inputs to the cycle include vitamin B12 and folate (as 5-MTHF) via the MTHFR (methylenetetrahydrofolate reductase) enzyme.
The main product of the cycle is SAMe (s-adenosylmethionine). SAMe is the body’s number one methyl donor, meaning it can donate methyl groups where they are needed for important body functions. (Source 1)
To learn more about this cycle and the role it plays in health, please read: The Methylation Cycle And Active B-12 and Methyl Folate.
Some other pieces of this cycle are also important to mention.
Homocysteine also has a short-cut back to methionine, one that doesn’t require vitamin B12 and folate, but requires the micronutrient choline (converted to betaine) instead, along with the enzyme BHMT (betaine homocysteine methyltransferase). (Source 2) This choline nutrient is quite important, and we will discuss it more below.
Homocysteine can also take another path besides returning to methionine. With vitamin B6 as cofactor and the CBS enzyme (cystathionine beta synthase) homocysteine turns into the amino cysteine, which plays many roles in the body. One important role of cysteine is in the production of glutathione, the body’s master antioxidant. (Source 3)
Elevated homocysteine levels are associated with heart disease and might be an indicator that the methylation cycle is running slowly. (Source 4)
Reasons for a slow methylation cycle might be deficiencies in vitamin B12, folate, magnesium, vitamin B6, choline, protein or other nutrients. A standard American diet may provide enough calories, but often falls short on important micronutrients that act as cofactors in biochemical processes.
In addition, many people have genetic mutations, called variants or SNPs (single nucleotide polymorphisms), in MTHFR or other key methylation enzymes that might slow down the methylation process. Variants in the genes that code for methylation enzymes are quite common.
Phosphatidyl Choline and Methylation End Products
As mentioned, SAMe is the body’s main methyl group donor produced by the methylation cycle. SAMe goes on to do many things, but the majority of SAMe goes on to produce two molecules:
- Phosphatidyl choline
Creatine is a compound made in the muscles and throughout the body from three amino acids: glycine, methionine and arginine. We also get creatine by eating meat and fish. Creatine production uses about 40 percent of the body’s available methyl groups. (Source 5)
However, phosphatidyl choline production is thought to use even more methyl groups than creatine! (Source 6) Production of each phosphatidyl choline molecule requires choline in addition to three methyl groups.
Choline is an important micronutrient, playing roles in neurotransmitters, methylation (as discussed above) and lipid transportation. As phosphatidyl choline, it is an important component of every cell membrane in the body and plays a role in cell signaling and communication. (Source 7)
Learn more about choline in my article: Phosphatidyl Choline Benefits: Brain, Liver, Gut and Cellular Function.
Most people don’t get enough choline in their diet, with intakes falling well below adequate for older children, men, women and pregnant women. (Source 7)
Without enough choline, the burden on the methylation cycle is even greater. The methylation cycle must churn out more methyl groups to keep up with choline production.
Here is the key point: Phosphatidyl choline (and creatine) production is so methylation intensive, but by having enough in the diet and as supplements, it spares the body from using the methylation cycle to make these molecules from scratch. And by doing so, frees up more methyl groups for important functions like DNA methylation, hormone production, neurotransmitter production, detoxification and more.
The result is a better mood, more energy, balanced hormones, stronger bones, improved fertility, decreased risk for chronic disease and so much more. Dietary and supplemental choline and phosphatidyl choline likely improves methylation in every cell of the body.
How To Optimize Methylation
When it comes to methylation, we want to support the methylation cycle to produce nice concentrations of methyl donors that we can use for all the body’s needs. We also want to take some pressure off the methylation cycle by making sure we have enough methylation end products coming in.
Here is how to do both:
- Use food as medicine. Here are the key methylation nutrients we discussed today along with important dietary sources:
- Vitamin B12 – All animal foods including, meat, fish, eggs, poultry, organ meat and whole dairy products.
- Folate – Dark leafy greens including kale, chard, spinach, collards and arugula, beans, avocados, oranges, liver, brussels sprouts, broccoli
- Choline – egg yolks, liver, red meat, poultry, fish, soybeans
- Creatine – red meat, pork, poultry and fish
Since food is medicine, give your body the best by choosing pastured, organic and regenerative options as much as possible.
- Avoid folic acid. Folic acid is the synthetic, inactive form of folate that is inexpensive and widely available. However, folic acid may be problematic for those with methylation dysfunction because it requires methylation to turn folic acid into active folate that the body can use. You think you are doing something supportive but are increasing the burden on the methylation cycle.
Folic acid is not only found in supplements, but also added to foods through fortification, such as protein powders, protein bars, breakfast cereals, refined flour, electrolyte drinks and more. Be sure to check all your labels!
- Use methylated vitamins for methylation support. It’s important to choose the active form of vitamin B12 as methyl B12 and folate as 5-MTHF (also called methylfolate).
Core Med Science offers Active Methyl B12 and Folate as a fast-acting lozenge, in Liposomal Active B- Complex + Minerals or as Liposomal B12 Folate and TMG. TMG (trimethyl glycine also called betaine) is another methyl donor. The body makes betaine out of choline.
- Use supplements to increase phosphatidyl choline. Core Med Science’s PC Complex is my go-to suggestion for methylation support. PC Complex contains a concentrated mix of phosphatidyl choline along with other phospholipid molecules that support cell membranes. You may notice improved energy production as well as better memory and cognition when you begin use.
Core Med Science’s supplements are unique in that they offer a liposomal delivery. Liposomes improve the absorption, bioavailability and effectiveness of supplemental nutrients because they mimic the body’s own cell structure. You guessed it – liposomes themselves contain phosphatidyl choline, giving all our products the added benefit of methylation support. We use sunflowers to derive phosphatidyl choline, making our products soy-free.
The main takeaway that I want to impart is that making phosphatidyl choline and creatine are the most “expensive” uses of methylation. When we ensure that the body has enough phosphatidyl choline, we take the burden off the methylation cycle for this purpose and free up methylation for other important things.
If you have a MTHFR mutation or other SNP or are having a hard time improving methylation status and related symptoms, understanding this phosphatidyl choline piece may be the missing piece.
- Froese, D. S., Fowler, B., & Baumgartner, M. R. (2019). Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. Journal of inherited metabolic disease, 42(4), 673–685. Abstract: https://pubmed.ncbi.nlm.nih.gov/30693532/
- Zeisel S. (2017). Choline, Other Methyl-Donors and Epigenetics. Nutrients, 9(5), 445. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452175/
- Wu, G., Fang, Y. Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of nutrition, 134(3), 489–492. Abstract: https://pubmed.ncbi.nlm.nih.gov/14988435/
- Kalra D. K. (2004). Homocysteine and cardiovascular disease. Current atherosclerosis reports, 6(2), 101–106. Abstract: https://pubmed.ncbi.nlm.nih.gov/15023293/
- Brosnan, J. T., da Silva, R. P., & Brosnan, M. E. (2011). The metabolic burden of creatine synthesis. Amino acids, 40(5), 1325–1331. Abstract: https://pubmed.ncbi.nlm.nih.gov/21387089/
- Stead, L. M., Brosnan, J. T., Brosnan, M. E., Vance, D. E., & Jacobs, R. L. (2006). Is it time to reevaluate methyl balance in humans?. The American journal of clinical nutrition, 83(1), 5–10. Full text: https://academic.oup.com/ajcn/article/83/1/5/4649586
- Zeisel, S. H., & da Costa, K. A. (2009). Choline: an essential nutrient for public health. Nutrition reviews, 67(11), 615–623. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782876/