Our Genes and Folate
Scientists sequenced the human genome more than 20 years ago! It’s taking decades to appreciate how our genes actually function. While most of us understand that DNA is the blueprint or building instructions for making living things, it turns out it’s not just a set of simple instructions. Instead, our genes are living and dynamic. Epigenetics is a growing field of science studying how our environment, actions, and behaviors determine our genetic expression. Simply, our environment, thoughts, diet and activities greatly influence how your genes are turned on and off. While we can control some of our genetic potential, there are variations that predispose some of us to certain health problems. A case in point are the genes that activate and process folate, which is referred to as MTHFR gene mutation.
One of the most common genetic variations in humans relates to this essential vitamin. Many have probably heard of neural tube defects in babies and the link to folate deficiency. While not getting enough folate in the diet is the simple explanation, there are many people who carry a genetic variant that prevents the efficient activation of folate. Folate status effects more than fetal development and recurring miscarriages. Issues with folate metabolism are commonly associated with infection, cancer, heart disease, and infertility. In addition, women are at risk for cervical dysplasia, pre-cancer of the cervix, by folate deficiency.
What is Folate?
Folate is a B vitamin that is essential for a host of biological activities, most notably, DNA replication and amino acid metabolism. Essentially, rapidly dividing cells need folate. Hence, why folate was first associated with birth defects. The consequences of folate problems go far beyond mother and baby. Folate deficiency was so widespread it led to the fortification of white flour with folic acid. There are naturally occurring “folates” and synthetic “folic acids.” The word folate or folic is derived from the word “foliage” since this nutrient is found in leafy green vegetables. Folic acid is the synthetic form that is used almost exclusively in supplements, prescriptions and in food fortification. While folic acid is believed to better raise levels in the body, it comes at a price. Folic acid may actually make the problem worse, as I’ll discuss further below.
The Folate-Gene Mutation Issue
The job of folate is to act as a coenzyme, transferring what are called methyl groups, chemically written as CH3 (a carbon atom with three hydrogens) from one molecule to another. This is necessary during DNA replication, growth and healing. Genes coding for an important folate activating pathway are referred to as the MTHFR genes, with the C677T variant being the most notable. It’s important to note that there are other genes that control folate metabolism such as A1298, but for simplicity we’ll discuss the most well studied related to these health problems. Up to 10% of the population has a “double” positive or is homozygous for the genetic variant of C677T and 20 – 53% are single positive or heterozygous. Since all our genes are in pairs, one from our mother, one from our father, we can either have one or two of the variants, or neither.
So what happens if you carry this gene variant? Those who have this trait can be less able to activate folate, therefore impairing blood cell production, healing, and immune response. Some of the most impacted areas of the body include the metabolically active organs of detoxification… the liver, kidneys, lugs, and digestive tract.
Chronic Illness and Folate
Immune health has been preeminent in recent history as the world experienced a novel viral disease. In order to mount an effective immune response you must have folate. In addition to needing folate directly for immune cell replication, the first line of defense, our epithelial cells of the respiratory, digestive tract, and skin need to replicate regularly, thereby providing a healthy barrier against invaders. Chronic infection or recurrent acute infections and the cascade of disease that can result are correlated with nutrient deficiencies. In addition to folate, adequate B12, B6, zinc, vitamins A, C, D and selenium are essential.
It is noteworthy that recent studies have shown that the MTHFR genetic polymorphisms are associated with the severity of the Covid19 disease. Essentially, poor folate status can lead to a worse illness when you encounter any number of human viruses. A common blood marker to look for besides gene testing is homocysteine. Elevated levels of homocysteine are associated with a poor prognosis from infection and cardiovascular disease.
Methylation and Detoxification
What about methylation and detoxification? The methylation pathway is essential for the elimination of certain toxic or unneeded metabolites. Including endogenous and exogenous toxic molecules that will be primarily eliminated via the liver. It also includes normal hormone metabolites that need to be regulated. Estrogen metabolism is an important area as it relates to common health problems we currently face, such as cancer of the breast, cervix, and prostate. “Slow-methylators” can have elevated levels of reactive estrogen metabolites that can damage your DNA and increase cancer risk.
Many cells in our body are capable of rendering toxins harmless or “tagging” for excretion, but the liver plays a primary role through two phases of detoxification allowing toxins to be excreted. This process requires a host of nutrients, but it is the phase II methylation process that is often lacking leaving some individuals with a higher toxic load or harmful hormone metabolites. Therefore, those with methylation genetic variants may be at increased risk for phase II deficiency and consequent diseases.
It’s important to realize that all of us can further burden our phases of detoxification and need for methylation by exposure to medications, smoking, vaping, alcohol, household, cosmetic, and industrial chemicals, and having a poor diet.
Dr. David Graves ND
Mutation or No Mutation – Be Vigilant!
While those with this genetic variant should be concerned about getting the right amount and form of folate, it turns out that even those without this trait need to be vigilant. There is some evidence that the synthetic form, folic acid, may actually block the pathways required to activate folate into its L-methyl form. L-methylfolate or 5-MTHF (methyltetrahydrofolate) is the most common active form of folate. Nearly all inexpensive and name brand vitamins use folic acid, the synthetic form. Thankfully if you know what to look for you can find the ideal form to supplement with.
*Seeking Health B12 L-5-MTHF Supplement – Great supplement for all ages! It dissolves in your mouth and doesn’t have a bad taste.
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How To Determine Your Folate Status
So what should one do to determine his or her folate status? First off, it goes without saying that most don’t eat enough folate-rich foods. Leafy greens, green herbs and many other vegetables should be the staple of the diet. It’s also relatively simple to take a high quality vitamin or B supplement with the active form of folate. You should consult your naturopathic or functional medicine doctor to determine how much to supplement with and if genetic testing makes sense for you.
Before simply loading up on folate or folic acid, note a few things to be cautious of. Taking excessive amounts of this vitamin can hide B12 deficiency. B12 is likely the most common vitamin deficiency in some demographics, especially the elderly and those on antacids and acid blocking medications. In addition, like all nutrients, folate requires a balance of other vitamins and minerals to function properly. Besides B12, it’s important to have the proper amount of B6 and riboflavin. Vitamin C has also improves folate bioavailability.
If you feel stuck in your health challenges, perhaps gene testing and other functional assessments would be of benefit. A simple vitamin like folate might be part of your story.
Article by Dr. David Graves, ND
Dr. Graves is a licensed Naturopathic Physician, receiving his degree from Bastyr University. His clinical focus is on functional endocrinology and has been practicing medicine for 13 years. In addition to providing in-person individualized care, he consults remotely with patients all over. He regularly writes health articles, and recently launched the Renascent Health Podcast, available for download from all the platforms. Dr. Graves resides in Spokane, WA and when not helping patients heal you can find him on the mountain bike trails.
I realized that to get at the root of most health issues you need to take a comprehensive look at the body’s dynamic function. We need to remove obstacles to healing and take a first-things-first approach to establish a foundation.
Dr. David Graves
You can find Dr. Graves at Renascent Health (renascenthealthnow.com) and sign up for his newsletter.
REFERENCES:
Folic Acid Increases Homocysteine – Dr Lynch : Dr Lynch (drbenlynch.com)
How The MTHFR 677 Gene Affects The Immune System | Nutrition Genome
Final Diagnosis — Case 677 (upmc.edu)
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