The neural tube is the hollow embryonic structure within a developing child from which the brain and spinal cord develop. Obviously, the central nervous system is of critical importance in human health. Anything leading to significant abnormalities in the development of that system would be a major attention grabber and focus of research. So it has always been with neural tube defects (NTDs). These run the gamut from subtle intellectual or physical disabilities to obviously disabling and often deadly spinal cord abnormalities or even failure of brain development. NTDs still occur in the US in over 3,000 births each year.
NTDs have been addressed for the past twenty years at the public health level by the “fortification” or addition of folic acid to processed grain products. In addition it has been addressed by stressing attention to providing folic acid in the form of prenatal vitamins to expectant mothers. The hope was providing this supplemental precursor to vitamin B9 could prevent as much as 80% of NTDs, which would have been a stunning achievement – and a major win for applied epigenetics. What actually happened can shed a lot of light on the complexity of individual nutritional needs and the emerging field of epigenetics.
The idea behind folic acid fortification came from how integral folate was in the biochemical pathways that controlled DNA synthesis. With that synthesis being particularly critical to the development of healthy neural tube tissues and structures. Folic acid isn’t the form of folate that the body uses in those pathways, but experiments showed that folic acid was actually absorbed better than “natural” folates. It also showed there was a pathway for the body to convert the folic acid to the active form through a multiple step process involving a number of enzymes and cofactors – so it’s all good, right? Unfortunately, continued research in folic acid
supplementation showed a reduction in NTDs closer to 35% than 80%. Furthermore, focused research seemed to show for some expectant mothers, folic acid supplementation (at recommended prenatal levels) actually increased their risk for delivering a child with neural tube defects (NTDs) – not a desirable possibility for a public health program.
In the pursuit of further insight through additional genetic testing, it became apparent that there were fairly widespread variations in the gene that builds the enzyme that converts folic acid into active, useful folate. The resultant enzyme is commonly referred to as MTHFR (for MethyleneTetraHydroFolate Reductase). Variations in the underlying genes are present, to some degree, in most people. Every variant results in an enzyme that has a reduced ability to produce activated folate, with impairments ranging from 15% to 75% depending on the combination.
The most limiting variants, when combined, are clearly associated with the worst outcomes – deadly NTDs. But that is still not the whole story. Remember how folic acid was better absorbed than natural folates? That turns out to be false assurance. Subsequent research revealed that the most effective activation of folates occurs at the mucosal lining of the small intestines. That is where the right machinery to do the job is readily available, and there is very limited capacity for activating folate beyond that barrier.
In other words, the rapid absorption of folic acid is a problem, not a benefit. It leads to circulating amounts of unchanged folic acid, which primarily acts to clog and impair folate-dependent enzyme pathways.
Conversion of folic acid to active folate involves quite a bit of “heavy lifting” biochemically speaking. Once it has bypassed the small intestinal mucosa, the odds are really against that happening in a timely fashion. Somewhat like how carbon monoxide dangerously combines much more easily with hemoglobin than oxygen does, circulating folic acid creates undesirable challenges to every pathway that properly activated folate would support. There are multiple variations of other important enzymes that provide essential “spinoff” products linked to folate metabolism.
Beyond avoiding NTDs, this area of biochemistry is involved in so many functions essential to wellness including:
- General Detoxification
- Regulation of Inflammation
- Operation of the Immune System
- Maintenance of the Circulatory System
- Healthy Balancing of Thought, Mood, Memory and Sleep
Addressing these issues, and setting them right, really must be on the “radar” for health coaches.
Dietary folates are in relatively short supply – especially in clients who may just be transitioning from a standard American dietary pattern. It will certainly take education to convince clients to avoid the public health recommended folic acid — in fortified foods and especially in supplements. There are additional cofactors for folate-dependent functions that can be equally scarce in the diet. Research has shown some very intriguing relationships — that the most common MTHFR variants seem to cause reduced effectiveness of folate conversion because of reduced interplay with specific cofactors. In these instances, epigenetic intervention with those cofactors can be of much greater clinical value than simply replacing the deficient end product (in this case activated folate – 5-MTHF).
Issues related to MTHFR genetics provide important illustrations for health coaches. Biochemistry reveals many interrelationships that influence multiple bodily systems and functions in ways that testing can usually provide some insight, but far from complete answers. Well-being can often be improved even when important markers like homocysteine, CRP, or other inflammatory measures are not at alarming levels. Individuals with complaints ultimately related to the same disruptions of pathways, may present with problems that seem unrelated because of how widely varied individual genetics and epigenetic influences may be on an individual’s wellbeing.
Health coaches have to be able to step back to see the most foundational needs, like a diet rich in sources of commonly scarce nutrients– no matter how well intentioned they may be (like folic acid). We need to be insightful when choosing supplementation where those needs are not likely to be met – based on understanding their client’s preferences and dietary habits. In doing so, we are trying to provide the broadest possible support (for every cell, tissue, and organ), out of respect for the intrinsic complexity of each individual’s needs (remember comprehensive incompleteness?) All the while we must be paying close attention to the process for the feedback (results or lack there of) that help move clients and future health coaching results forward.