If you’ve struggled most of your life with depression and nervousness, or even tend to feel a little down in the dumps, you might want to check to see if you are undermethylating. Methylation status something I regularly check patients for because it’s a process the body needs to run diverse and vital functions, but oftentimes their methylation processing isn’t quite balanced – causing them to undermethylate or overmethylate.
Last week I published an article about overmethylation because I felt like it is a topic that is not commonly addressed and yet effects many people. Of these two sister conditions, undermethylation tends to get more of the attention but still it’s important we clarify the differences, some common misconceptions, and a natural treatment options so you can do your best to reduce its impact in your life.
So let’s briefly revisit methylation. Methylation is a biochemical process used throughout your body like a little light switches for turning on repairing DNA, producing energy, regulating hormones, detoxification, synthesizing neurotransmitters, and more. Undermethylation occurs when someone doesn’t have enough methyl groups to switch on certain processes. Most people methylate properly but if you fall on either end of the spectrum, you’re going to feel it.
12 Symptoms of Undermethylation
Though undermethylation and overmethylation both share anxiety as a symptom, people who are experiencing a lack of methylation are typically experiencing anxiety that’s more geared towards perfectionism tendencies. Where as people with overmethylation tend to have extreme anxiety accompanied with panic attacks in some cases.
Here are 12 symptoms of undermethylation:
- Fatigue
- Depression
- Insomnia
- Nervousness and perfectionism
- Addictions
- Low serotonin activity
- Headaches
- Obsessive compulsive behaviors
- High libido
- Allergies
- Ritualistic behavior
- Digestive issues
Undermethylation is associated with MTHFR mutations C677T, A1298C, MS, BHMT, MAT and SAHH. Please keep in mind that when you get a genetic test, you getting a list of possibilities and it is not definitive to whether or not you are undermethylating or overmethylating. That being said, it’s a good way to know which way your body might tend to behave.
What Causes Undermethylation?
There’s a common misconception that the genetic mutations associated are what cause under or overmethylation. However, it’s not that simple. While genetic mutations might make it more likely that you’re not methylating enough and there are also likely environmental causes. Toxin and mold exposure, high-stress environments, nutrient deficiencies, and even emotional trauma seem to potentially affect methylation in the body.
While there’s no one definitive cause of undermethylation, if you come to the conclusion that that’s what’s happening in your body and causing your symptoms, you’ll want to address the underlying causes by restoring the related factors. When it comes to naturally healing your body so it begins to methylate at a normal rate, it’s a good idea to make sure you’re getting enough precursors, co-factors, and supporting your body’s detoxification processes.
An Undermethylation Diet
Here are some of those precursors and cofactors you should add to your diet to help with your undermethylation:
- Choline – An important methyl donor.
- Glutathione – Low glutathione levels can impair methylation.
- Copper – Many methylation enzymes require copper for reactions.
- Magnesium – Plays an important role and gene methylation.
- Folate – An important methyl donor.
- Zinc – Insufficient zinc levels can reduce the body’s ability to use methyl groups.
- Vitamin B2 – Helps recycle folate so it’s a usable methyl donor form.
- Vitamin B3 – Maintains proper methylation of genes, which helps resist tumor formation.
- Vitamin B6 – A cofactor for an important enzyme that helps transfer methyl groups.
- Vitamin B12 – A key enzyme used in the synthesis of your body’s most important methyl donor, S-adenosylmethionine (SAMe).
- SAMe, methionine, or TMG can also be taken
Foods to avoid:
- Vegetable oils
- Processed foods
- Gluten
- Soy
Foods to enjoy:
- Organic fresh vegetables
- Grass-fed beef
- Wild caught salmon
- Full fat yogurt
- Eggs (if tolerant)
Basically, the key here is to eliminate things that often cause people problems such as common food sensitivities and inflammatory foods. It’s going to be really important for you to go on a whole food plant-based diet. Then you’ll want to focus on the nutrients listed above because they are essential for methylation.
Juicing probably won’t feel great for you because there’s high concentrations of folic acid, which can cause people who are undermethylating problems. Folic acid depletes methyl groups in the nucleus of the cell where DNA is made. Outside the nucleus, folic acid can actually contribute to the methyl groups in your body. This can be confusing because it seems to contradict itself, but the most important thing to remember is that folic acid usually inhibits detoxification processes and therefore it doesn’t feel great for somebody who’s undermethylating.
You’ll also likely benefit from reducing histamine in your diet. This is because high histamine levels and undermethylation are associated.
Undermethylation & Histamine
Another thing that can contribute to undermethylation besides the MTHFR gene mutations and environmental causes, are high levels of histamine in the body. Histamine is an important mediator released by your mast cells to cause acute inflammation. Histamine gets a bad name but in reality we need histamine to help get important immune system elements to injuries and to attack Invaders. That being said, it’s fairly common to experience high histamine in such a way that it becomes problematic.
What can contributes to histamine levels?
- Overactive mast cells
- Fermented foods
- Cured meats
- Smoked meats
- Canned foods
- Pickled foods
- Leftovers
Noticing a theme in the foods listed above? This is because as foods sits, it breaks down and creates histamine.
Undermethylation Treatment
If you suspect undermethylation is causing you problems, I encourage you to seek out the help of a functional medicine doctor with experience in this area. Through testing and careful recording of your diet and lifestyle, you and your doctor should be able to help you reduce the number of factors that are contributing to your undermethylation.
If you’re interested learning more about overmethylation, I encourage you to check out my blog: Is Overmethylation The Cause of Your Anxiety?
Resources:
https://www.ncbi.nlm.nih.gov/pubmed/16825685
https://www.ncbi.nlm.nih.gov/pubmed/9461031
https://www.ncbi.nlm.nih.gov/pubmed/15627265
https://www.ncbi.nlm.nih.gov/pubmed/19812675
https://www.ncbi.nlm.nih.gov/pubmed/18950248
https://www.ncbi.nlm.nih.gov/pubmed/21939673
https://www.ncbi.nlm.nih.gov/pubmed/11916749
https://www.ncbi.nlm.nih.gov/pubmed/16939485
https://www.ncbi.nlm.nih.gov/pubmed/20920744
Thank you so much for this post! Do you go into more detail about the efect of folic acid on undermethylation anywhere? I’ve read Nutrient Power by DR. Walsh and what he says about folic acid having a negative impact on mood and emotions for people who are undermethylated seems to hold true for me. Supplementing with P5P, methionine and avoiding folic acid seems to be helpful but I’m still trying to find balance with my methylation. You seem to be very knowledgable and I would love to hear more from you on this topic.
I also became depressed when I took folate. I was compound heterozygous for C677T and A1298C, so it seemed like folate supplementation was a no brainer. I had testing recommended by Dr Walsh and did well on his recommended supplements, with no folate. (I eat a salad every day). He said folate is an epigenetic modifier, and will pull the methyl off the histones which in this case turns on the reuptake pumps, thereby decreasing neurotransmitters in the synapse. He has an impressive amount of data and had actually noted the odd response of some of his patients before the research caught up with him and provided an explanation. I am a little concerned about the seeming universal recommendation for everyone to take methyl folate if they are genetically susceptible. It may not be the best answer for everyone.
Ditto! I am homo 677t and have put my mind and body into absolute hell through experimental folate supplementation these last few years. I believe it is all neurotransmitter related. Would love to get more reading on what it going on. I have done a urinary amino acids test which showed most aminos as low, and particularly low in methionine. I also have done a Nutreval test that shows elevated figlu, and functional high deficiencies of folate, b1, b12, and biotin. I am very sensitive to glutamates, which folate are a chain of, and also histamine, and curious of how folate, FIGLU, histamine, and glutamates are all related to what otherwise looks like someone is undermethylated. Could methionine be my answer? Ugh, this is all so frustrating and no doctors in California I can find that specialize.
What kind of testing should a functional medicine practitioner be doing to evaluate methylation status?
I do genetic testing to evaluate for SNPs and methylation panel from Doctors Data but there are other ways such as organic acid testing
We only have organic acid testing at hand, which markers can tell under or over-methylation ?
is it Uracil or Thymine ? Thank you so much for your advice ~
Good ‘short’ article on a very deep and complex subject. One thing people might want to note here that was not mentioned; Low methylation can impair glutathione levels, so someone can have methylation and glutathione levels near crash and stay at those levels, very nasty.
I have A1298C heterogeneous and will be going to see a functional medicine doctor later this month. In the mean time my endocrinologist recommend a few methyl vitamins, B6, and alpha linolenic acid to see if that helps my fatigue and a few other items. I read in this article some foods to eat and avoid. What is the reasoning to avoid gluten?
many patients are sensitive to gluten and i you have any autoimmune disease it may be a trigger
Much appreciated explanation of methylation that I have so often fumbled to explain to my patients. I will quote you in the future! Thanks for sharing and I always get so much out of your webinars. Keep up the great work.
Can you explain more about why low serotonin and high libido can both be symptoms of UM? I was told that libido will be low if serotonin is low.
No that is incorrect. Many drugs that raise serotonin will decrease libido
I’m confused about folate (listed above as helpful nutrients for undermethylators) versus the folic acid found in juice (listed as not helpful) as I though that folic acid was the synthetic form of folate and that is what is to be avoided for anyone with MTHFR SNPs. Also, doctors like Ben Lynch recommend activated folate like L-5–Methytetrahydrofolate but other doctors like Walsh say folic acid is a no go (but he doesn’t mention the activated form, so maybe that’s ok)? Any help with clarifying what’s what? Thanks!
I had the same question, Kiki. I was really hoping there would’ve an answer!
Hello…what are considered a high and low whole blood histamine levels in regards to over and under methylation determination?
Thanks for the help Jill
Hi Mike
It depends on the labs ranges. Typically I use LabCorp and the appropriate ranges will be listed
Warmly
Dr Jill
Thanks Jill….I’m right dab smack in the middle of labcorps range, which is quite wide. Its hard to imagine somebody being lower than a 15. What mainly determine’s the difference in one’s histamine levels? Do they vary greatly from day to day ? When I look at Walsh’s characteristics of over and under methylators I find i can identify with characteristicstics of both. Where I can look at some people and clearly tell what they are.
Thanks, Mike
Dr. Jill, in the list of substances to add to an undermethylation diet you mentioned folate (vitamin b9) and call it a methyl donor. While it does donate methyl to the cell as a whole, folates rob the nucleus of the cell of methyl. This is mentioned in Dr Walsh’s book Nutrient Power as well as in numerous videos by Dr Albert Mensah.
This is why undermethylators tend to deteriorate quickly on high folate diets. It’s the overmethylators that are encouraged to add more folate to their diets.
This is not to say that undermethylators don’t need some folate, just not much.
I felt much better after both removing the excess vegetables from my diet and also treating my pyrrole disorder.
Undermethylation, overmethylation, copper toxicity and pyrrole disorder should be checked in all mental health persons due to those four conditions making up 90 percent of all underlying causes.
thanks for your wonderful comments, Justin