In the human body, methylation refers to the donation of a methyl group (an alkyl composed of one carbon bound to three hydrogens) to some substrate, facilitated by methylating enzymes (cofactors for which include folate, vitamin B6, and vitamin B12). An introduction to the entirety of methylation processes in the body is obviously outside of this article’s scope, so let’s limit our focus to the roles of methyl groups in genetic expression, protein function, and free radical quenching. Methyl groups and their donors can be seen simplistically as one of the body’s chief organizers which direct many facets of functionality according to one’s unique blueprint. Without an adequate quantity of methyl donors or an adequate degree of freedom for the gamut of methylation processes to operate, a large list of health problems can easily arise.
For instance, methyl donors are crucial for the operation of the phase II detoxification pathway in the liver, and many hormones, endogenous metabolites, and toxicants compete for the agents used in the phase I and phase II detox pathways. Thus, if the body is heavily toxic, methylating agents can be stolen from pathways throughout the body (such as those related to exercise adaptation) to assist in detoxification. Similarly, a lack of methyl reserves also worsens the susceptibility of mitochondria and mitochondrial DNA to damage from reactive oxygen species and toxins, the result of which would be a hindering to the body’s capacity to generate usable energy in the form of ATP as well as adequately respond to exercise demands. Additionally, a decrease in ATP production can lead to a drop in mTOR’s signaling for protein synthesis or muscle repair [1].
Because folate (not to be confused with folic acid, a synthetic compound) is one of the main methylation cofactors, a deficiency in this nutrient can easily disrupt the synthesis, repair, and methylation of DNA, and such a disruption could obviously impair the body’s ability to positively adapt to the exercise stressors imposed upon it [2]. Expanding upon this example, the compound “S-adenosyl-methionine” (SAM) primarily serves as the chief methyl donor for the body. Once SAM gives up its methyl group, it is reformed into S-adenosyl-homocysteine. If there is enough usable folate and vitamin B12 available, S-adenosyl-homocysteine can ultimately be converted back into methionine through the homocysteine intermediate. However, if the body is under notable stress (e.g. oxidative stress from exercise or toxic stress from heavy metals, microbial infection, or toxicant exposure), it may divert homocysteine from its regular cycle so that it can be used in manufacturing glutathione, a primary antioxidant and detox agent. This diversion reduces the available concentration of SAM.
Along the same lines, it’s very important to note that the synthesis of creatine typically stands as the largest consumer of the body’s methyl reserves [3]. So, if your methylation demand is excessively high from stress or toxicity in some form, your body may divert resources away from creatine synthesis and toward more vital processes – weakening the phosphagen system’s contribution to exercise performance. For this reason, increasing the body’s supply of creatine (through dietary or supplementation means) can serve to positively buffer your consumption of methyl reserves and allow for you to more effectively adapt to exercise. Though it’s worth noting that synthetically-derived creatine may have an energetic profile that differs from that produced naturally within animal tissue (even though the chemical structure is equivalent).
Now, methylation capacity can be diminished from the outset due a variety of issues, such as a single nucleotide polymorphism (or SNP) involving the MTHFR gene, the presence of Leaky-gut, or low levels of stomach acid. If you’ve been struggling with plateaus in your training, you may have one or more of such underlying issues – I recommend consulting either a competent Functional Medicine practitioner or a Naturopathic physician if you suspect this may be the case.
If you are unable to replenish your methyl reserves after experiencing a deficit (whether due primarily to pre-existing conditions or an accumulation of stress/toxicity), then not only will you be placed into a downward spiral of catabolism in which your body is unable to recover and adapt to exercise, but you will also be laying the tracks for the development of a myriad of chronic disease states. This downward spiral consists largely of the body becoming locked into a continual activation of the stress response in which cellular inflammation and the no/onoo cycle (repeated elevations in peroxynitrite, nitric oxide, and others) end up running rampant [4] [5]. Once this state is attained, you can pretty well forget about making fitness gains.
The last point I want to mention here is that some methyl donors are needed in order to convert the thyroid hormone T4 into T3 (the more active form), so if you have a lack of methylating agents to begin with or a large portion of these agents are being used elsewhere (to deal with more pressing problems), then again you’ll have a tough time with exercise performance and adaptation.
In conclusion, I hope this article helped to highlight the importance of methylation capacity in not only improving your health, but your level of fitness as well. Take care.
MNT DT
