This article broke it down some, but wasn't going quite as deep as the video at the bottom of the article. I'll put that here so you can watch if you like. But what I did is take notes while watching the video, and I'm sharing that work with you here, because it makes a lot of sense, and I believe it can make positive change for many people!!
So here's what I printed off and am sharing with my doctors. You are welcome to do the same! Feel free to share far and wide. This is new information and it really really matters. Today's offering is just with regards to MTHFR and how it affects thyroid conditions. So without further ado, here's my crazy long notes session! The video link is in the first paragraph of text below, but here it is if you just want to watch here:
Feel free to copy/paste, print, and share!
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MTHFR Gene Mutation and Specifically How it Affects the Thyroid
Dr. Alan Christianson and Dr. Ben Lynch explain the MTHFR genetic disorder, and why it matters. What specific problems does this genetic disorder cause, and what that means for these patients. The purpose of this video is to show the connection to a vast majority of thyroid disorders: https://youtu.be/7WxQOn_CAHI
Dr. Lynch founded MTHFR.net and is the President/CEO of Seekinghealth.com
There are 3 tiers to nutritional status: There’s what we get in (Diet, supplements), there’s assimilation and there’s this genetic variability on activation. This (MTHFR and folic acid metabolism) can be the missing link for key nutrients, and it’s not for lack of availability, and it’s not for lack of absorption.
"The functions of folate in human physiology are relatively simple, but the implications of their activity (and dysfunction) can be profound and far-reaching."
Functions of folate in the body:
- synthesis of nucleic acids (DNA repair, tRNA)
- If you’re not repairing and building your DNA on a daily basis, it will lead to problems, especially in the gut.
- single carbon metabolism (methylation)
- turns on and off different genes
- creatine, coq10, carnitine, phosphatidylcholine, (and more!) all require methylation for metabolism/use in the body
- interconversion of amino acids (neurotransmitter production and detoxification)
- Neurotransmitters like Serotonin, melatonin, and certain compounds like histamine require methylation and folate
- formation and maturation of RBC, WBC, and platelet production
- Blood cell creation
- Folate is CRITICAL
- On a fundamental chemical level, most every major reaction your body does depends upon folate, and if it’s not right, so many parts of our health can be impacted by that
“Folic acid” is NOT equal to “folate”. It's only ONE type of folate, and must undergo various transformations to be utilized. Be specific if discussing folic acid! Is it Folic acid, Folinic acid, or Methylfolate?
“Folate” is the biological active form of what your body uses of the different types of folate.
- “Folic acid” is a synthetic man-made form.
- Designed to be shelf-stable.
- Intended to prevent neural tube defects, which it has
- For those with MTHFR (50% of the population!), however, it’s not the form to choose. It’s not found in nature, and it has to go through a whole bunch of different reactions in the body in order to be used properly. (image below)
- “Folate” is an umbrella term, like “car” for “Honda”, “Volvo” etc
What’s the difference between “Folic acid” and “5-Methyltetrahydrofolate” (or “Methylfolate”)?
- The little red circle, CH3, is the difference. This is the methyl group. The part that allows the methylation to occur.
How does a healthy body change Folic acid into methylfolate?
At the very top, we have Folic Acid. This comes from fortified foods and supplements.
DHF, down one step, is another kind of folate, from the diet, in the form of natural (not enriched) foods like uncooked leafy greens and beans
Simply skipping supplements and intaking dietary folate makes a big difference
The process to change Folic Acid to DHF is a very slow dramatic process, so it can accumulate in the blood. The problem with this is Unmetabolized Folic Acid, down to the right from Folic Acid. But this UMFA can inhibit part of your natural immune system, specifically the natural killer cells
Simply skipping supplements and intaking dietary folate makes a big difference
The process to change Folic Acid to DHF is a very slow dramatic process, so it can accumulate in the blood. The problem with this is Unmetabolized Folic Acid, down to the right from Folic Acid. But this UMFA can inhibit part of your natural immune system, specifically the natural killer cells
Neither the speed of the conversion nor the UMFA build up in the blood are good for our bodies. And while Dietary folate is far superior to supplemental folate, in that it won’t build up in the blood like the supplemental form can, it still isn’t going to be enough to create methylfolate if the MTHFR enzyme is defective.
The other enzymatic steps (not detailed in the video) lead to the end-product, 5-MTHF (methylfolate). Just above this is MTHFR, the enzyme Dr Lynch has been focused on since 2010. It’s been such a big focus because it is showing itself to be a big deal!
See the B2 sticking on MTHFR? This is a very specific form of Riboflavin. It is a required cofactor for conversion of the dietary folate to the final usable form, methylfolate.
See the B2 sticking on MTHFR? This is a very specific form of Riboflavin. It is a required cofactor for conversion of the dietary folate to the final usable form, methylfolate.
Conversion from Folic acid to methylfolate requires the following:
- Two functioning enzymes
- MTHFD1
- MTHFR
- Vitamins, Minerals, and PH
- B2
- B3
- B6
- B12
- Vitamin C
- Zinc
- Acidic environment (for absorption~ NO ANTACIDS!)
What are the risks that come with taking/consuming fortified foods with Folic Acid if you have MTHFR genetic defect?
- UMFA, leading to immunity issues (lowered numbers of natural killer cells)
- Too much folic acid is linked to higher risk of colo-rectal cancer.
- It can mask B-12 deficiency, which can cause DNA methylation problems
A few different versions of MTHFR enzyme issues:
heterozygous: 1 copy of the gene from either parent
homozygous: 1 copy of the gene from each parent
MTHFR C677T heterozygous: 40% loss of function to convert from folate to methylfolate
MTHFR C677T homozygous: 70% loss of function to convert from folate to methylfolate
MTHFR A1298C heterozygous: no detectable loss of function to convert from folate to methylfolate
MTHFR A1298C homozygous: slightly decreased methylation
MTHFr C677T & A1298C compound heterozygous: 50% loss of function to convert from folate to methylfolate
Riboflavin (B2) more rapidly disassociates (falls off) from the altered (C677T) MTHFR enzyme, rendering it unstable. The means the enzyme won’t work very well, and it can produce the methylation problem.
MTFHR Defects:
The following are SOME conditions they cause (a fraction of issues that is known to be connected). This is everywhere, folate metabolism often seems to affect something or other downstream in the body, because it is so central to our biochemistry. This is why the MTHFR defect affects so much else in the body.
The following are SOME conditions they cause (a fraction of issues that is known to be connected). This is everywhere, folate metabolism often seems to affect something or other downstream in the body, because it is so central to our biochemistry. This is why the MTHFR defect affects so much else in the body.
- Diabetes
- Cancer
- Pulmonary Embolisms
- Cleft Palate
- Spina Bifida
- Autism
- Parkinson’s
- Neural Tube Defects
- Atherosclerosis
- Immune Deficiency
- ADD/ADHD
- Multiple Sclerosis
- Alzheimer’s
- Dementia
- Chemical Sensitivity
- Congenital Heart Defects
- Fibromyalgia
- Chronic Fatigue Syndrome
- Depression
- Alcoholism
- Addictive Behaviours
- Insomnia
- Down’s Syndrome
- Chronic Viral Infection
- Thyroid Dysfunction
- Neuropathy
- Recurrent Miscarriages
- Infertility
- Anxiery
- Schizophrenia
- Bipolar
- Allergies
Who is at risk?
Mexicans, Italians, Northern Chinese, and Hispanics have a much higher chance of having these variants. Spanish, French, Hungarian, white USA population, Israelites, Southern Chinese, white Australians, Russians, Canadian whites, Finns (Finland), black USA population
Approximately 45% of the world population has 1 copy of MTHFR C677T.
Many studies show it’s only something to treat if you have elevated levels of homocysteine. But this is not accurate because MTHFR is only one path to lower homocysteine levels. There are many ways available to test for the MTHFR gene mutation (as of 2013):
- Spectracell
- Quest
- LabCorp
- Baylor Research Institute is an excellent out of pocket option if insurance does not cover
- 23andMe provides only raw data which must be interpreted. Interpretation is available through www.MTHFRSupport.com or www.geneticgenie.org
- Any Lab Test Now
- Life extension foundation might (they weren’t sure at the time of the video)
Insurance MAY cover (as of 2013) IF one has experienced:
- Drug sensitivity - especially to methotrexate or nitrous oxide
- Recurrent blood clots
- Elevated homocysteine levels
- Recurrent miscarriage
There are drugs to help treat this, mostly those that contain the methylated form of the vitamins that the MTHFR-affected body cannot metabolize properly.
The Methylation Process and why this all matters:
In the left circle, you’ll see the 5-MTHF reductase. And where that left circle intersects with the big circle, you see B-12 in various forms. It connects to an enzyme called Methionine synthase on the bigger circle.
These are like 2 gears that need each other to work properly to turn the circles. If one side has isn’t turning, the other side stays still too. Folic acid is incredibly important here, as is B-12, to make that left side turn.
The SAM in the upper right side in the right circle is SAM-E, a popular supplement for decreasing pain, and supporting depression, and this is how we make our own! Glutathione (bottom of the bigger circle, all the way right) is also made by these processes.
These are like 2 gears that need each other to work properly to turn the circles. If one side has isn’t turning, the other side stays still too. Folic acid is incredibly important here, as is B-12, to make that left side turn.
The SAM in the upper right side in the right circle is SAM-E, a popular supplement for decreasing pain, and supporting depression, and this is how we make our own! Glutathione (bottom of the bigger circle, all the way right) is also made by these processes.
MTHFR in thyroid disorder (pulled chart info from screen on video):
Graves’ Disease
|
Graves’ Disease
|
Hashimoto’s Disease
|
Hashimoto’s Disease
| ||
Intractable
|
In Remission
|
Severe
|
Mild
| ||
MTHFR
rs1801133
+677C/T
|
CC
|
27 (36-5%)
|
13 (27-7%)
|
15 (40-5%)
|
25 (45-5%)
|
MTHFR
rs1801133
+677C/T
|
CT
|
36% (48-6%)
|
25 (53-2%)
|
18 (48-7%)
|
28 (50-9%)
|
MTHFR
Rs1801133
+677C/T
|
TT
|
11 (14-9%)
|
9 (19-1%)
|
4 (10-8%)
|
2 (3-6%)
|
MTHFR
rs1801133
+677C/T
|
C Allele
|
90 (60-8%)
|
45 (59-2%)
|
58 (61-7%)
|
78 (71-0%)
|
MTHFR
rs1801133
+677C/T
|
T Allele
|
58 (39-2%)
|
31 (40-8%)
|
36 (38-3%)
|
32 (29-0%)
|
MTHFR
rs1801131
+1298A/C
|
AA
|
43 (55-1%)
|
28 (62-2%)
|
26 (57-8%)
|
29 (63-0%)
|
MTHFR
rs1801131
+1298A/C
|
AC
|
34 (43-6%)
|
17 (37-8%)
|
18 (40-0%)
|
15 (32-6%)
|
MTHFR
rs1801131
+1298A/C
|
CC
|
1 (1-3%)
|
0 (0-0%)
|
1 (2-2%)
|
2 (4-4%)
|
MTHFR
rs1801131
+1298A/C
|
A Allele
|
120 (76-9%)
|
73 (75-7%)
|
48 (80-0%)
|
73 (79-3%)
|
MTHFR
rs1801131
+1298A/C
|
C Allele
|
36 (23-1%)
|
17 (24-3%)
|
12 (20-0%)
|
19 (20-7%)
|
677 variant: CC/CT. C is good, T is bad. One T is bad, 2 T’s are even worse.
One copy being bad is roughly 50% of the population. Adding the percentages for mild (50%) and severe (48%) adds up to nearly 100% of all Hashimoto's’ patients. Adding the Intractable (48%) and remission (53%) is also nearly 100%. The overall total of thyroid disease patients and MTHFR is 99.9% of all thyroid patients. There is an incredibly strong link here. If you have any type of thyroid disorder, you most likely have MTHFR gene mutation.
Back to B2, Riboflavin! With the 677 variant it’s difficult for the B2 (Riboflavin) to attach itself to the defective MTHFR enzyme, thus it doesn’t work well. You end up needing higher levels of riboflavin for the MTHFR to stabilize if you have the mutation. “Studies showed that the MTHFR cofactor, FAD (the most active form of Riboflavin) could protect the mutant enzyme from destabilization, suggesting that Riboflavin, the precursor of FAD, should be considered as a modifier in enzymatic activity, and consequently, high levels of blood homocysteine.“
Riboflavin as FAD for MTHFR, Demonstrating Effectiveness
“Riboflavin supplementation targeted at hypertensive individuals with MTHFR 677TT genotype can decrease BP more effectively than treatment with current antihypertensive drugs only”
So insufficiency of riboflavin would make the other MTHFR problems even more pronounced.
Nutritiondata.self.com for more info on how to be sure to get enough riboflavin in the diet. Some options include: liver, yeast extract, almonds, cheese, wheat bran, fish, sesame seeds, and tomatoes.
Just like, to convert Folic Acid to Methylfolate, the body needs B2 and MTHFR, and to methylate, the body needs B12, MTHFR, and folate, the conversion from Riboflavin to the usable FAD requires thyroxine.
“Thyroxine (T4) regulates the conversion of riboflavin to riboflavin mononucleotide and flavin adenine dinucleotide (FAD)... Thyroxine therapy resulted in normal levels of this enzyme... Thyroid hormone regulates the enzymatic conversion of riboflavin to its active coenzyme forms in the human adult”
So insufficiency of riboflavin would make the other MTHFR problems even more pronounced.
Nutritiondata.self.com for more info on how to be sure to get enough riboflavin in the diet. Some options include: liver, yeast extract, almonds, cheese, wheat bran, fish, sesame seeds, and tomatoes.
Just like, to convert Folic Acid to Methylfolate, the body needs B2 and MTHFR, and to methylate, the body needs B12, MTHFR, and folate, the conversion from Riboflavin to the usable FAD requires thyroxine.
“Thyroxine (T4) regulates the conversion of riboflavin to riboflavin mononucleotide and flavin adenine dinucleotide (FAD)... Thyroxine therapy resulted in normal levels of this enzyme... Thyroid hormone regulates the enzymatic conversion of riboflavin to its active coenzyme forms in the human adult”
If you have untreated thyroid disorder, you need more FAD, but you cannot form it. So you’re in double-trouble with thyroid and MTHFR.
This is a physiologic need for Thyroxine (T4), as opposed to just T3 or T2. While there’s been argument on having replacement therapy on just T3, and Dr. Christianson likes to have all the bases covered, this is an argument for being the only therapy.
In many cases T4 is considered to be just the source of the other hormones but there are things that suggest it is needed by itself, and this is another thing to add to that list.
Those that have been on T3 only therapies may need to reconsider their regimen, with this new information in mind, with regards to the importance of T4 to Riboflavin to FAD conversion.
This is a physiologic need for Thyroxine (T4), as opposed to just T3 or T2. While there’s been argument on having replacement therapy on just T3, and Dr. Christianson likes to have all the bases covered, this is an argument for being the only therapy.
In many cases T4 is considered to be just the source of the other hormones but there are things that suggest it is needed by itself, and this is another thing to add to that list.
Those that have been on T3 only therapies may need to reconsider their regimen, with this new information in mind, with regards to the importance of T4 to Riboflavin to FAD conversion.
Expression of MTHFR and FAD availability in Thyroid Disorders
The present (2013) study indicates that thyroid status affects the phenotypic expression of the MTHFR677CT polymorphism by modifying FAD (riboflavin) synthesis. This mechanism could partly explain how thyroid dysfunction affects the metabolism of folates and homocysteine. The thyroid hormone itself affects the MTHFR enzyme.
Danger of Excess
If you have a LOT of Thyroxine (Grave’s Disease) you’ll be producing MORE FAD, and if you have more active riboflavin, then you are going to be pushing the MTHFR enzyme faster, and you’re going to have a potentially reduced homocysteine levels. You do need homocysteine, at the right levels, to produce Sam-E, glutathione, etc. If you have too LITTLE Thyroxine (Hashimoto’s) you will produce everything else much slower.
And! If you have Thyroid Disorder of any kid, even if you do NOT have MTHFR defect, you still have an MTHFR-like inhibition by having reduced thyroxine. If you’re in that low % of people who do not have the MTHFR genetic defect, you still need to treat it like you do have it. This brings the thyroid disorder need to treat all the way up to 100%. Sam-E is another important piece of this puzzle. It’s your main methyl-donor in the body, and if you don’t have methylation happening properly, it means you’re not turning on and off your genes properly. You’re not repairing the cells throughout the body, setting the body up for inflammatory disorders, and cancer. This is how MTHFR is connected to thyroid cancers.
If you have a LOT of Thyroxine (Grave’s Disease) you’ll be producing MORE FAD, and if you have more active riboflavin, then you are going to be pushing the MTHFR enzyme faster, and you’re going to have a potentially reduced homocysteine levels. You do need homocysteine, at the right levels, to produce Sam-E, glutathione, etc. If you have too LITTLE Thyroxine (Hashimoto’s) you will produce everything else much slower.
And! If you have Thyroid Disorder of any kid, even if you do NOT have MTHFR defect, you still have an MTHFR-like inhibition by having reduced thyroxine. If you’re in that low % of people who do not have the MTHFR genetic defect, you still need to treat it like you do have it. This brings the thyroid disorder need to treat all the way up to 100%. Sam-E is another important piece of this puzzle. It’s your main methyl-donor in the body, and if you don’t have methylation happening properly, it means you’re not turning on and off your genes properly. You’re not repairing the cells throughout the body, setting the body up for inflammatory disorders, and cancer. This is how MTHFR is connected to thyroid cancers.
As you push MTHFR to work, you’re converting homocysteine to methionine, which is great. Methionine (MET) converts to Sam-E (upper right on the big circle) which is a principle contributor of DNA Methylation. It helps control a few important enzymes in the body:
On the left, near the SAM-E in the DNA Methylation area, you’ll see DNMT1, DNMT3a, and DNMT3b. These are DNA methyltransferase enzymes, and all very important for embryological development and in preventing cancers.
MTHFR c677T and thyroid cancer
Study: Increased T-allele frequency of 677 C>T polymorphism in the methylentetrahydrofolate reductase (MTHFR) gene in differentiated thyroid carcinoma. (How MTHFR C677T gene mutation plays a role in thyroid cancers)
- If you have MTHFR C677T, you have a higher risk of thyroid cancer. But it’s nothing to be crazy worried about, just be proactive with your doctor about screenings. If you haven’t had an ultrasound done, get one done, even if you feel okay on your current treatment. Get regular followups to compare to that original ultrasound, to watch your thyroid more carefully!
Positive Ending: Knowledge is power. Just optimize your environment and your diet and supplements. And be proactive with the known increased risk factors of this issue.
So where do we go from here?
Test for MTHFR to see if you have it and if you do, which type is it? - Watch your thyroid hormones.
- Get your thyroid ultrasounds started and keep them up to date
- Watch your B2 (riboflavin), methylfolate, B12 and other nutrients through a quality multivitamin. Find a physician who will work with you and your biochemistry.
- And you have to optimize your lifestyle to maintain good health. Be proactive.
- Let food be thy medicine. Read labels. Restrict your synthetic folic acid, and if you have a medical need for it, switch to methylfolate and folinic acid.
More resources and information:
All information was pulled from this video: https://www.youtube.com/watch?v=7WxQOn_CAHI
Their resources and some more information is in the info area under the video as well.
Notes compiled by Rebecca J Harris on 11-7-17. The notes are all taken while watching this video, none of this content is my intellectual property.
Notes compiled by Rebecca J Harris on 11-7-17. The notes are all taken while watching this video, none of this content is my intellectual property.
