The following is a sneak-peek draft Answer to a feature Question for the pending Manuscript entire re-writing and rebranding to sufficiently complete. Live-it-forward  ~ AW.

"How does fasting affects my Methylation status?"

This is difficult to address considering variabilities of an individual's parameters ~ existing fitness, age, sociological and physiological circumstances to name a few.

However, This Author (AW) would be more inclined to conclude, given his own experience - that daily intermittent fasting including occassional prolonged fast(s) should not significantly ~ affect methylation status in a way terminally or clinically "adverse".  Indeed, stress response is necessary as part of experiencing any changes, alongside the anxiety and/or hunger transients.

For as long as outside / structural stress is firstly be addressed sufficiently; presuming that is readers are not living in a semi-developing or third world geography ~ one would simply not “die” akin to that terminal illnesses, or extreme frailty simply by intermittent fasting, alone.

For all its worth, a noteworthy lecture by Chris Masterjohn (2017) (14:15 onwards) informs that even before gene expressions can or possibly be affected, as indicated by homeostatic balances between the major methylation donors (Creatine, Phoshpadytyl Choline, SAME) ~ “Extreme Malnourishments” must be occuring presumably under a considerable period of time.

A conventional thought amongst skeptics suggests that lack of calorie intake in general, or simply CR / calorie restriction practice ~ prompts an increase overall stress hormones and thereby detriment to overall methylation. Fasting included, as some skeptics argue, is a form of stress. Amidst devout followers of Dr. Raymond Peat strongly argues it prompts cancer growth.

This Author’s (AW) own nutrigenomics testing suggest that intermittent fasting is reportedly “harmful”, indicated by his “slow” COMT status. There appears to be a sentence-claim (xcode.life) , though not detailed enough in its argument ~ that fasting may slow this COMT metabolism by the given increased catechols during the fasting window.

But other than the above short proclaim as well as resounding fears of IF effects on general mortality ~ are there research proclaiming the opposite? Indeed. Research on IF’s effects on psychological health remains likewise praised. Two research reviews (Berthelot, E. et al. 2021) & (Fernández-Rodríguez et al. 2022) examined dozens of studies, including RCTs - and concluded there are indeed benefits noted; even amongst type 2 diabetics practicing just 14 hours of fasting, which arguably is very accessible to many. Another review on 500+ articles involving IF trials on senior adults likewise found improvement amongst those with depressive and anxiety symptoms (Sharifi S, et al. 2024) .

One question nonetheless rarely addressed - is whether or not that fasting, as a form stress, is akin to that as an “exercise”. Exercise alone, as one can expect (and who would dare not) ~ brings together a whole sleuth of inflammatory markers. Very inflammatory ones at that. Including not limited to nitric oxide, Hydrogen Peroxides, and byproducts of FFAs / free fatty acids / 4HNEs for instance.

Are all these responses legitimately appropriate? In more than likelihood ~ This Author (AW) would respond as a resounding “Yes”. And how would this affect "Methylation", specifically, as one practices Fasting? This Author (AW) proclaim once again that regular “exercise” alone, including intermittent fasting, so long as calorie intake is sufficiently replenished ~ would not be enough to cause severe depravations. 

Considering the above citations, and likely dozens internally referenced more within each of them; all compelling their own mechanistic findings and hypothesis. One may argue and conclude that there are much more practical and readily-felt implications, despite its difficult and elusive perhaps effects on methylation alone ~ that IF / fasting remains arguably, a safe and tolerable intervention.

In light of all the above it remains obviously sensible - that contingents should be considered, were we to maintain this as sensibly as we can, long term. Some of which that may not only benefit surrounding topics of “Methylation” but directly and intuitively from their practical effects that readers likewise can readily felt - assisting anywhere from digestion, quelling feelings of unease between heavy meal intakes, mental acuity / No-tropics and overall resilience ~ to name a few ~ Methylfolate, Methylcobalamin (B12), SAMe, Betaine Hydrochloride with Pepsin, Creatine Monohydrate, and additional Choline (as Phosphadrytl Choline or Choline Bitartrate).

Besides worrying whether or not "Methylation" adjusts autonomously, there are lot more other "changes" and/or "adjustment" effects that we inevitably will and have to brace with IF and calorie restrictions. Not with fear. But with open Science for our own self-hood.

"Metabolism", for instance adjusts likewise as we present ourselves with enough challenges, including prolonged fasts, as we tinker what foods satiates which doesn't, what foods comforts our gut and what doesn't. "Slowing metabolism" down is another. It is arguably a blessing in and of itself. Considering that we are still alive, somehow - by experiencing things anew that we wouldn’t dare to otherwise.

All these and more cumulatively builds our own self discoveries.Without trying, or without finding out through such experiences ~ we may as well perhaps be forever ignorant of our own potential.

Live it forward,

AW.