I recently had a patient come in with a very expensive genetic report regarding methylation pathways evaluating whether or not they had an alteration, called a SnP, to the methylation genes. The methylation pathways include enzymes like MTHFR, MTRR, COMT and AHCY. I know, this is just alphabet soup for most but there are some important takeaways.
When MTHFR awareness first hit the public, I would get panicked calls of people wanting to urgently get in to see me because they had an abnormal “MTHFR”. To calm your fear right off the bat, this is something you are born with and most people aren’t even aware they have a problem in these pathways. I have been looking at the MTHFR and COMT pathways for 15 + years. When I first dove into this, I was suspect of a link between defects of these pathways to certain medical conditions. However, I have learned that the body is quite masterful is finding ways around these defects.
Let’s clarify the true importance of the methylation pathways, do you really need to be tested with gene testing and answering the real question of how these pathways are working. Hint, heart disease and moods will be a big part of our discussion…..
READ ON ….
MTHFR defects called polymorphisms or SNPs are present in 85% of the population! That number should immediately help you relax if you do have one of these variants. MTHFR stands for methylenetetrahydrofolate reductase and MTRR stands for methionine synthase reductase so you can see why we use the abbreviations. Both are involved in the synthesis and utilization of folate. Genetic discussions are always challenging so I want to break this down as simply as possible. Each gene has two legs (visualize a person). When both legs are the whole with no damage the gene is said to have no SNP’s and are “normal”. When one leg is damaged the gene is said to be heterozygous. When both legs have damage, the gene is said to be homozygous. MTHFR has two variants and to keep this simple we will call one variant the C/T and one A/C. The degree of damage affects the function of the enzyme however it still functions! Snps in the different genes results in different levels of dysfunction. For example, a heterozygous Snp (one leg damaged) will result in a 35% activity reduction of the MTHFR C/T gene. The homozygous Snp (both legs damaged) will result in a 70% activity reduction for the MTHFR C/T gene but only a 40% reduction in the MTHFR A/C gene. This is already complicated enough so I want to stop with all the technical data. The take home message is even with both legs damaged (homozygous) the genes do work. The REAL question is not which gene is damaged but what happens to the function when they are damaged.
I used to measure the MTHFR gene SNPs all the time when insurance actually covered the tests. I still measure it when I am working with anxiety, depression and some heart disease patients. Insurance doesn’t cover this test and right now Boston Heart Lab offers the testing for $50 looking at only the MTHFR variants. There are other more expensive tests available that look at the MTHFR, COMT and AHCY genes but after reading this you may realize that you don’t really need all that information in most cases.
Understanding how the methylation pathway is working is probably more important than knowing which variant you have! There are several tests that can give you this information.
- Homocysteine: When homocysteine is elevated then there is increased inflammation. Numerous studies have linked high homocysteine to heart disease, birth heart defects and some other illnesses. This is easily measured in routine labs however, medicare and some other insurances won’t pay for this test but many do!! Levels above 10 would be considered elevated and indicative of some part of your methylation pathway not working. The MTHFR C/T and MTRR genes are the guiding factors regarding homocysteine so if you have an elevated homocysteine you most likely have some type of defect in one or both of those pathways. The higher the number the more likely it is both legs or perhaps both genes are affected. The MTHFR A/C gene defects do NOT raise homocysteine and therefore thought not to be as significant as the C/T in heart disease as a result but very important for mental health.
- Whole blood histamine. This test is done thru Labcorp and is not really measuring histamine levels but is an indicator of how your methylation pathways are working. The higher the level the more likely you have a variant in one of your genes. It is important to view these lab values in an “optimal” range and not the “normal ranges” reported by the lab. Significant mood disorders may occur when this is elevated even at the higher end of the normal range!!
- SAM/SAH ratio. This marker is a measure of a methylation index. Methylation is driven by an adequate SAM supply and SAH removal. This marker can indicate if you have hypo (too little) or hyper (too much) methylation. Yes, you can have too much methylation but that’s for another day. Let’s get a bit geeky so you can see the other components of some of the methylation gene tests: SAM (s adenosylmethionine) is converted to SAH (s-adenosylhomocysteine) via an enzyme called COMT. Once SAH is formed it is converted to homocysteine via an enzyme called ADOhcy. So, MTHFR, MTRR, COMT and ADOhcy enzymes are all involved in the methylation pathways!
I know, I know this is not easy to understand so let me spell this out. I would rather you spend your $ on understanding how this pathway works than getting stuck on which variants you have!! Do I still measure the MTHFR? Of course, but not without thinking about the other moving parts and understanding exactly what I am looking for. For me, knowing if you are heterozygous or homozygous is important primarily for dosing considerations.
I want to highlight one at risk population that do have some solid studies… young ladies wanting to get pregnant. As more and more information comes to light, there have been studies linking high homocysteine to some heart defects all via these methylation pathway defects. If you normalize the homocysteine it would stand to reason that these risks may be lowered although I haven’t seen in formal studies looking specifically at this. While methylfolate is considered a key vitamin to address methylation, trimethylglycine is even more important especially in pregnant women who you don’t want to give too much folate supplementation (they do need folate but not in high doses). Take home message – if you are wanting to get pregnant check your homocysteine before you start trying! Your primary care physician can order this test and you already know the level needs to be below 10!
Stay tuned because next week I want to dive into the mental health symptoms associated with undermethylation and overmethylation. You may be surprised that your anxiety, depression, OCD, bipolar, schizophrenia, insomnia are all tucked into these pathways!!
To your health,
Laura
