I first learned about the methylation cycle when I was trying to improve my marginal health and trying to get pregnant with my daughter at the age of about forty-one. I learned about a few of the most talked about methylation genes like MTHFR and found out that I was homozygous for A1298C. My OB said that, that may explain many of the problems I had been experiencing like chronic fatigue. Little did she know that my family history had multiple issues related to the MTHFR gene alone.
My brother had open heart surgery at the age of ten for a hole in his heart. My nephew has high functioning autism. There is ADHD in my family as well as chronic fatigue syndrome and fibromyalgia. There is a very long list of health issues that could have roots in certain SNP’s single nucleic polymorphisms. I had done the most research on MTHFR and my daughter also has the double MTHFR A1298C. That SNP was one of the reasons that a doctor wrote my daughter a medical exemption for vaccines in 2018.
As I said I had done a bit of research on MTHFR which is the one I mentioned to my daughters doctor but I had not really looked as deeply into it as I thought I should have. MTHFR was only one small part of the methylation cycle which is critical to wellbeing and health. I am going to hopefully share a few things below about methylation and why it’s so important so you can decide what you might want to do to address any SNP’s you have that could be negatively affecting your health through marginal nutrition.
DNA methylation and autoimmune disease research on PUBMED says a mouthful about the fact that without proper methylation you can get autoimmune disease and affects the immune system, “DNA methylation plays an essential role in maintaining T-cell function. A growing body of literature indicates that failure to maintain DNA methylation levels and patterns in mature T cells can result in T-cell autoreactivity in vitro and autoimmunity in vivo. Defective maintenance of DNA methylation may be caused by drugs such as procainamide or hydralazine, or failure to activate the genes encoding maintenance DNA methyltransferases during mitosis, resulting in the development of a lupus-like disease or perhaps other autoimmune disorders. This paper reviews the evidence supporting a role for abnormal T-cell DNA methylation in causing autoimmunity in an animal model of drug-induced lupus, and discusses some of the mechanisms involved. T cells from patients with active lupus have evidence for most if not all of the same methylation abnormalities, suggesting that abnormal DNA methylation plays a role in idiopathic human lupus as well.” https://pubmed.ncbi.nlm.nih.gov/14585278/
I have a bit of a focus on autoimmune diseases because I have three of them, EOE, psoriasis, and endometriosis (which has long been corrected). My son has a family history of autoimmune issues in his family and there was suspicion of IBD in Jessica several years ago. So, some of the research that I look up focuses on autoimmune diseases. Jessica has clearly had issues with her immune system for a long time.
An article entitled The emerging role of epigenetics in human autoimmune disorders talks about epigenetics which is what understanding and addressing the methylation cycle can help one to do with nutrition. “Epigenetic pathways play a pivotal role in the development and function of the immune system. Over the last decade, a growing body of studies has been published out seeking to explain a correlation between epigenetic modifications and the development of autoimmune disorders. Epigenetic changes, such as DNA methylation, histone modifications, and noncoding RNAs, are involved in the pathogenesis of autoimmune diseases mainly by regulating gene expression.” https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0632-2
This article goes on to say that DNA methylation is one of the most studied epigenetic marks, “DNA methylation is one of the most studied epigenetic marks and typically occurs at the pyrimidine C5 position of cytosine residues by transferring a methyl group from S-adenosyl-L-methionine (SAM) through the catalytic action of DNA methyltransferases (DNMTs) [4,5,6]. DNA methylation influences a large variety of biological processes such as transcriptional repression, reversible promoter silencing, and chromosomal instability [7, 8].” https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0632-2
“One of the crucial functions of DNA methylation is the maintenance of the T cell regulation. Recent findings underlined the critical role of DNA methylation in numerous autoimmune diseases by altering gene expression profiles [12,13,14,15]. Several factors such as environmental influences, genetic variants, drugs, and miRNAs influencing the DNA methylation status have been linked to autoimmune disorders.” https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0632-2
I love the two women who blog at www.autoimmunewellness.com Micky Trescott who went to a weekend training on methylation by Dr. Ben Lynch who has done a lot of research on this topic. She writes the following a simple description of the importance of methylation, “What is Methylation?–Simply put, methylation is a biochemical process that occurs in every cell in our bodies countless times throughout the day. For the chemistry nerds—it is the addition of a methyl group (a single carbon atom bonded to three hydrogen atoms) to a compound. Its proper functioning is absolutely essential for optimal health—just check out the list below:
Functions of Methylation:
Gene regulation and expression
Neurotransmitter production (which affect everything from mood to digestion and sleep)
Hormone processing (especially Estrogen)
Building immune cells (T and NK cells)
DNA and histone synthesis
Producing myelin (protective coating on nerves)
Building and maintaining cell membranes
Because it is so essential to health, when methylation is impaired, it can affect almost any organ or system of the body. Some of you in the autoimmune and chronic illness communities are probably familiar with the MTHFR mutation, or other genetic mutations that can impact methylation (more about that in the next part of this series!).
Here are some ways methylation can be disrupted:
Lack of nutrients (folate, B12)
Lack of cofactors (zinc, b2, magnesium, cysteine, b6)
Certain medications (antacids, methotrexate, metformin, nitrous oxide)
Nutrients that deplete methyl groups (niacin)
Environmental toxicity (heavy metals and other chemicals)
Excessive cofactors in the diet
Excessive stress, anxiety, and sleep disturbances
Genetic mutations (like the MTHFR genes we will we be talking more about)” https://autoimmunewellness.com/methylation-series-part-i-methylation-and-folate/
Chris Kresser simply describes methylation on his website, “Methylation is a vital metabolic process that happens in every cell and every organ of our body. Life would simply not exist without it. It takes place more than a billion times per second in the body.” https://chriskresser.com/methylation-what-is-it-and-why-should-you-care/
He goes on to talk about how methylation affects detox and is required to make glutathione, the master antioxidant in the body extremely necessary for getting rid of all kinds of toxins.
“We know now that environmental factors like diet and stress and sleep and toxins lead to molecular changes that are not encoded in DNA, so they’re not actually changing the hardware of the system, if you want to use a computer analogy. But those changes are still passed down to children and even grandchildren, so even though they’re not affecting the hardware, they are affecting the software, and the software, in a sense, is passed down to the children in a way that can affect their hardware or can affect the health of future generations…methylation is the main mechanism of turning off and on of genes.” https://chriskresser.com/methylation-what-is-it-and-why-should-you-care/
Dr. Amy Yasko has several books and works mainly looking at lab results and recommending supplements for the nutritional aspects of the methylation cycle. Methylation is a critical process for the body for many reasons. It’s a complex process I am not going to go into detail here but in Amy’s book Feel Good about your SNPS; roadmap to your health she says while explaining the reason to give certain supplements that could make other metabolites or products you don’t want in the body, “The reason is that we need The Methylation Cycle for critical functions in the body. Methylation is needed to silence virus, to myelinate nerves, to make new T cells (so that we’re not making auto antibodies, to respond properly to infectious agents and to reduce allergic inflammation), to make new DNA (i.e. to repair gut lining), for neurotransmitters, for DNA regulation, detoxification of environmental toxins and the list goes on.” Pg. 68
A few other important things that Dr. Amy brings up about methylation, “Part of what makes The Methylation cycle so unique and so critical for our health is that mutations in this pathway have the capability to affect other health factors. This would suggest that if an individual has enough mutations or weaknesses in this pathway, it may be sufficient to cause multifactorial health issues. Methylation Cycle mutations can lead to chronic infectious diseases, increased environmental toxin burdens and have secondary effects on the expression of other genes…the impacts of methylation can literally last for generations. Recent studies found that grandmaternal stress during pregnancy had effects as far reaching as the third generation of children…research has shown that the degree of DNA methylation predicts all cause mortality. In other words, no matter what you look at in terms of a cause of death, the degree to which methylation is functioning in your system influences the age at which death occurs. Taken together with my own observations, this suggests that some methylation cycle SNPs must be so significant that they are not even consistent with life. Or put another way, there are some SNP combinations that I never see as they may be lethal, this should help all of you understand why I feel it is critical for all of us to pay attention to our SNPs in this nutritional pathway and use natural supports to achieve better balance for a longer healthier life.” pg. 40-42
Since COVID-19 is a good example possibly to describe what’s happening with methylation because we’re all interested in the outcomes of COVID and Jessica and my husband Doug have COVID right now as I write this. Listen to what the article Blood DNA methylation and COVID-19 outcomes has to say about methylation, “Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score.
Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148415/
“Critically ill patients exhibit altered circulating blood DNA methylation profiles [24, 25]. Epigenetic marks affect gene expression profiles and increase individual vulnerability to viral infections” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148415/
For example, immune-modulating drugs such as corticosteroids, that are beneficial in COVID-19 patients [7, 37–39], interact with gene expression-response elements throughout the genome. Resolution of the differential methylome in COVID-19 patients offers potential insights into COVID-19 pathogenesis, susceptibility, diagnosis and prognosis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148415/
There is a study called the Agouti mice study which shows what the mother ate affects the expression of genes in the baby mouse. Making sure to get proper vitamins will make obesity genes NOT express where that is what the baby mouse should have inherited. See the following information about this study; https://www.youtube.com/watch?v=GoMVNGEbNag, Agouti: from mouse to man, from skin to fat https://pubmed.ncbi.nlm.nih.gov/11837451/. The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome https://academic.oup.com/nutritionreviews/article/66/suppl_1/S7/1939970.
Listen to this passage from an article entitled Mother’s diet changes pups color very astounding results, “This study presents a valuable model system and underlines the influence of outside factors on gene expression, says geneticist Wolf Reik of the Babraham Institute in Cambridge, UK. “It highlights the fact that external events are important,” he says. “We need methods for looking at methylation in human tissues Wolf Reik, Babraham Institute” But extrapolating from mouse to man needs more data on human methylation, Reik warns. “We need methods for looking at methylation in human tissues,” he says. What’s more, the Agouti mice received 3-20 times their required daily level of the tested nutrients. Scaled up to humans, such doses would be huge. “We shouldn’t panic at this stage,” Reik jokes. In humans, about 40% of DNA is methylated – mostly to de-activate rogue, nomadic DNA elements that lurk throughout the genome, which can cause disease if left unchecked. Many genes are also methylated, including the cancer-causing p16, and a host of ‘imprinted’ genes, one copy of which is de-activated after fertilization.
Imprinting changes are linked with certain cancers, and with congenital disorders such as Angelman syndrome and Beckwith-Weidemann syndrome2. If diet affects the methylation patterns of imprinted genes, it could play a role in such conditions.” From online Nature magazine https://www.nature.com/articles/news030728-12
Another article describing the same agouti mice study is DNA is not destiny; the new science of epigenetics https://www.discovermagazine.com/the-sciences/dna-is-not-destiny-the-new-science-of-epigenetics
I did the very best that I felt I could do pre-pregnancy and during pregnancy but so many things seemed to go wrong that I had no control over, I am not sure how it all affected my daughter with her cellular health and how that continues to affect her or will affect her in the future. All you or anyone can do is do the best you can. I do believe that the good nutrition before, during, and after pregnancy did help for sure to give her a better foundation than had I not done anything.
If you have issues with your health or you’re trying to get pregnant seek out more information about Methylation from your functional medicine doctor or even selected internet searches of scientific journals, books, and information that can lead you to help and answers for your health.