L-Leucine: along an inverse axis to flush niacin in modulating energy metabolism

Technically speaking, the leucine dose will depend on the amount needed for the sufficient, desired, and/or optimized effects of flush niacin to come to fruition; for many, for recovery, a dose of at minimum, 1,000 mg up to usually 2,000 mg of l-leucine in tandem/combo with usually at least a 500 mg (to make sure) dose of flush niacin may be sufficient to harness some further benefits, though aging adults and/or individuals with persistent muscle weakness (i.e., COVID-19 affected especially) may need higher l-leucine dose starting out, i.e., up to potentially at least 4,000 mg, even up to 6,000 mg for a few doses.

In fact, to start out, perhaps everyone seeking at least moderate-level of recovery/better health should take advantage of higher dose of l-leucine (around 5 g for average-weight adults) to allow flush niacin alongside then to provide (closer to) full activation of the niacin GPR109A receptor infrastructure. With these relatively higher, earlier doses of l-leucine, it would also be logical to make sure that if they are too high for whatever reason, there is enough flush niacin coming alongside (and in this way, what should provide more therapy as well). In this fashion, it would be best to not venture too high with the leucine dose (really, even take any leucine) without at least a dose of 1,000 mg flush niacin (at minimum, 100 mg) alongside. While leucine will potentiate/augment harnessing and activation of niacin’s powers, it may be most efficient, especially for high levels of recovery sought, to provide an equimolar amount of niacin alongside (i.e., 90% (or 0.90) times) as much niacin coming with leucine each time (e.g., 5,000 mg l-leucine would be with 4,500 mg flush niacin). If not ready to go that high with flush niacin, whatever the highest you can (and at minimum, just to be safe, 500 mg with that dose in which l-leucine is at 3,000 mg or more). In emergency/severe acute situations, the powers of flush niacin are certainly more harnessed the sooner after the fact, but some l-leucine still should ensure to augment the benefit provided by flush niacin. Notwithstanding the importance of leucine, especially in these urgent situations, it is crucial to not administer any leucine without (sufficient) flush niacin, as this will further expose the need for niacin that is not being addressed. Utmost, a high dose of flush niacin (at least 3,000 mg) would be the primary treatment here, administered alongside with at least l-leucine (+ ideally, other cofactors; see below) at 2,000 to 3,000 mg.

Evidently, those who have not had much success with flush niacin (with or without R-lipoic acid and/or melatonin, etc. alongside), especially those who have experienced bothersome reactions trying to reach the needed higher doses, are indeed those that necessitate flush niacin the most. However, in this lies the paradox: how to achieve these higher doses most smoothly for the most efficient recovery to ensue? Well, in these situations, the lack of leucine is what appears to most fundamentally impede niacin to induce more therapy and instead lead to these caveats. Recouping leucine then alongside flush niacin (from the get-go) at the needed dosing, is what should allow even lower doses of flush niacin (starting at even around 100 mg) to start working, of course not as much as higher levels of niacin then, but it would then allow these folks to readily hit the higher needed doses (as niacin will finally start working and not be excess like crazy each dose and lead to undesired reactions while therapy was impeded as it was before without incoming sufficient leucine).

As recovery clicks and entails, one can likely start lowering l-leucine each dose forward by 100-200 mg (but keep niacin wherever it needs to be). Give 1-2 nights of sleep usually to evaluate if recovery is coming after whatever levels of combined dosing of the two together, and if so, then keep the niacin there (maybe tad higher at most then) while moving the other direction (i.e., lower) with l-leucine dose. If the feeling-better pattern continues, keep the same method going and even start lowering niacin to comfort. If not, then return to the earlier higher levels of leucine and niacin that were working well (even raise them together, particularly leucine if niacin is as high as at least 1,500 to 2,000 mg). We may necessitate a minimum level of l-leucine provided alongside just to finally start harnessing niacin, so do not be afraid to go higher with the l-leucine (assuming niacin is high enough alongside) in that if therapy is not yet ensuing it likely means too low of leucine still and/or still not all B vitamins recouped (namely folic acid B9; see below).

Do not be surprised if, erratically, some days or averages of weeks, doses of niacin and/or leucine are higher/lower than usual. Again, we likely will not need as much niacin as we used to for similar effects that can now be fully realized and achieved via meeting leucine requirements alongside for complete signaling to continue for niacin each time. Nevertheless, we ultimately want to reach and achieve a point where we can continue to provide leucine and niacin in unison (at whatever is closest to the ideal levels of the two) in balance to continue promotion of energy metabolism homeostasis. Likely, as health restores, the dosing of the leucine and niacin in combination eventually may modulate out to equimolar doses of the two in unison as indeed the ideal combo for dynamic maintenance of thermodynamic equilibrium, and perhaps for therapy as well. Therefore too much leucine in diet w/o compensatory niacin leads to classic pellagra; and accordingly, why those who now need high flush niacin to cure, need higher leucine alongside. The two seem to cancel each other out, and the point where we would not need either is at the hypothetical instantaneous point of “steady state”, i.e., health, homeostasis. Clearly, we will not require as much (and/or as often) of either or both to dynamically maintain a life that remains as near to homeostasis as possible, as we did to get there (i.e., recover).