Like everything else we talk about, MTHFR and vitamin D have a curious relationship. Vitamin D doesn’t link into the folate cycle, the methylation cycle, or the BH4 pathway so it isn’t an obvious connection, but it’s thought to be linked through the sharply named “Folate-Vitamin D-UV Hypothesis of Skin Pigmentation.” So let’s break this down along with a couple of gene SNPs that affect vitamin D specifically.
Vitamin D
Vitamin D is a fat soluble vitamin that is sounds like a miracle in the research, helping to prevent everything from depression to cancer. It helps you build strong bones by increasing absorption and retention of calcium and phosphorus. It reduces cancer cell growth, helps control infections, and reduces inflammation. Research also found a link between high vitamin D levels and protection from the most severe consequences of Covid-19.
Research has been booming about vitamin D for the last fifteen to twenty years, and startlingly it has shown that roughly 24% of the US population is vitamin D deficient and almost 6% of the population is severely so. Vitamin D deficiency has been implicated in:
- Autoimmune conditions like lupus and MS
- Diseases of aging like Alzheimer’s and dementia
- Mental health issues like schizophrenia and depression
- Atopic conditions like asthma and eczema
- Bone diseases like osteoporosis and rickets
- Hormone issues like PMS and repeat pregnancy loss
- Inflammatory conditions like IBD and tooth and gum decay
- Other conditions like cancer, ADHD, and erectile dysfunction
Vitamin D is found in a small number of foods including egg yolk, oily fish, red meat, mushrooms, and liver. The bulk of the vitamin D in your body, however, is produced via a chemical reaction between sunlight and your skin. Specifically, it needs ultraviolet radiation on your skin.
Gene SNPs that Affect Vitamin D Levels VDR Bsm and VDR Taq.
VDR gene SNPs actually code for vitamin D receptors, so this isn’t in the manufacture of vitamin D per se, it’s in the ability to metabolize, transport, and use Vitamin D. There are other gene SNPs that are emerging for Vitamin D, but these are the most frequently studied.
VDR Taq
This gene is associated with both vitamin D levels in the blood and also with muscle growth and bone density on strength training. The CC variant, which is the wild type, is generally linked to high vitamin D levels, as well as greater muscle growth and bone density with strength training exercise. The TT variant, is associated with lower vitamin D status and less muscle growth and bone density in response to strength training. The CT form is somewhere in the middle.
BDR Bsm
This gene is associated with immunoprotection, bone mineral density, and also short stature. The wild type, or GG allele, has lower risk of bone density issues, normal stature, and more typical immunity. The AA allele has a higher risk of bone density problems, is more likely to be short in stature, and may have specific types of immune compromise. The AG allele is somewhere in the middle of those two states.
Managing VDR Gene SNPs
The relationship between these gene SNPs and pathology depends entirely on vitamin D levels, so the clear path to balancing out VDR gene SNPs lies in boosting vitamin D levels. This is where we leave solid research and enter my own musings and supposition, so take this as a well educated guess and nothing more.
The typical “normal” range for vitamin D on blood tests is broad – between 20 ng/mL and 100 ng/mL. Although there is some debate about what constitutes an optimal number, for most people I think hovering somewhere around the 40 – 50 ng/mL mark seems logical. Not too close to the lower limit, but also not pushing crazy high numbers for no reason. For people with VDR polymorphisms, I encourage numbers closer to 70-80 ng/mL simply because if your body has trouble transporting, metabolizing, or using vitamin D, then giving it a higher background level may help to compensate. Again, this is my own supposition and hasn’t been particularly well researched yet.
The complicated relationship between Folate and Vitamin D.
This is actually interesting, because it’s a departure from the usual chemical pathways that we typically talk about. Folate is sensitive to ultraviolet radiation, so the more time you spend with your skin in direct sunlight, especially on high UV-index days, the more folate is used within your skin. This happens because UV light generates free radicals within your skin, and folate acts as an acceptor for those free radicals, essentially doing the duty of an antioxidant in this situation, to help protect your vulnerable tissues from damage.
Folate also works overtime donating methyl groups to DNA that gets damaged by UV radiation, essentially helping to protect your skin from the mutations that would lead to skin cancers.
The bottom line here is that UV exposure uses up folate reserves while UV exposure generates Vitamin D.
There is a remarkable theory of human evolution, the afore mentioned “Folate vitamin D UV-hypothesis of skin pigmentation” that states that skin pigment evolved as humans migrated northward out of Africa to maximize and balance levels of both folate and vitamin D because they are both so pivotal for successful reproduction as well as overall health.
This theory states that skin pigments were concentrated and skin remained dark in areas close to the equator to buffer some of the effects of the tremendous amount of UV exposure, but still allow enough for vitamin D processing. Therefore, people with darker skin pigment actually need more sunlight exposure to manufacture enough vitamin D, and their folate is well protected by the pigments. People who migrated northward were becoming vitamin D deficient due to lack of adequate UV exposure and so evolution favored lighter skin pigments that require less UV exposure to make adequate vitamin D, but that also leave folate more vulnerable to UV-related breakdown.
Vitamin D and MTHFR – A Supportive Relationship?
Because of the contrary relationship between folate and vitamin D with UV exposure, it’s becoming a research target. An interesting study published in the journal neurology, found that in children with ADHD, which has known linkages with both MTHFR and low vitamin D status, the effects of MTHFR on vitamin D weren’t entirely what the researchers predicted.
Children with the C677T homozygous polymorphism (so TT or two mutant copies) actually had higher vitamin D levels than individuals with the CC allele or the “wild type.” Individuals with a heterozygous mutation, or CT allele, were somewhere in the middle.
The researchers theorized that because people with MTHFR need to conserve folate, and therefore need to avoid prolonged UV radiation exposure, they have developed some mechanism to manufacture or maintain vitamin D levels more efficiently.
“As such, individuals with MTHFR TT may manufacture and/or maintain vitamin D more efficiently due to their genetic need to avoid prolonged UVR exposure. Hence, vitamin D levels may be higher at baseline in children with MTHFR TT status.”
Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and associated vitamin D levels in children with Attention-Deficit/Hyperactivity Disorder (ADHD) (P5.6-043)
Sarah Silverstein, Keith Pecor, Asher Junger, Jeffrey Kornitzer
Neurology Apr 2019, 92 (15 Supplement) P5.6-043;
Thank you so much for listening today.
Is Vitamin D Affected by MTHFR?
Vitamin D levels are not directly affected by the MTHFR gene SNP, but these two elements do have a relationship around UV light exposure. Vitamin D is created in human skin using UVB radiation, and so increases with UV light exposure. Folate, on the other hand, is used to quench the free radicals in skin that are created by UV exposure, as well as to repair DNA damaged by UV exposure. This means that more UV light exposure leads to higher vitamin D levels, but lower active folate. For people with the MTHFR polymoprhism it is important to be mindful of UV exposure and to make sure to get vitamin D from other sources as well.
MTHFR Gene Carriers: What Should They Avoid?
The MTHFR gene SNP influences people’s ability to activate folate, and makes active folate and methyl groups a more limited resource in the human body. There are a number of things MTHFR gene carriers should avoid, but two of the biggest are folic acid, the synthetic form of folate, and excessive sunlight expsore because UV radiation uses massive amounts of active folate. Folic acid is detremental to people with the MTHFR variant because it makes the conversion to active folate worse and is more difficult to metabolize. It is also important for people with the MTHFR gene SNP to avoid foods fortified with folic acid.
How Should Someone With MTHFR Supplement Their Diet?
MTHFR is a gene SNP that impairs people’s ability to activate the various forms of folate into the form most used by the body, which is methylene tetrahydrofolate, or 5-LMTHF. Because of this, people with the MTHFR polymorphism need to make sure they get an MTHFR-safe form of folate such as 5-LMTHF, if it’s tolerated, folinic acid, or natural food sources of folate as well as methyl donors. Methyl donors could include 5-LMTHF, methylcobalamin (the methyl form of B12), choline, SAMe, and TMG. Additional vitamin D might also be necessary in some situations. It is crucial that people with the MTHFR mutation avoid folic acid, the synthetic form of folate, which makes this condition worse.
Does Taking Folic Acid Affect People Who Have MTHFR?
MTHFR polymorphisms are genetic variances that affect people’s ability to metabolize the various forms of folate into the active form. Folic acid is the synthetic, crystaline form of folate and some research has indicated that it makes MTHFR polymorphisms worse and can even create a “pseudo-MTHFR deficiency” in peopel who are genetically normal if it is taken at doses above the recommended level.
MTHFR is a common genetic mutation that can contribute to anxiety, depression, fatigue, chronic pain, infertility, and more serious conditions like breast implant illness, heart attack, stroke, chronic fatigue syndrome, and some types of cancer. If you know or suspect you have an MTHFR variant, schedule a free 15-minute meet-and-greet appointment with MTHFR expert Dr. Amy today.
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