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| Additionally, it's noteworthy that two MIB-626 trials utilized a twice per day administration regimen. This dosing schedule is significant because it could potentially offer more consistent NAD+ level support throughout the day, although the specific implications of this frequency in relation to circadian rhythms and overall efficacy remain an area for further research.{{pmid|35182418}}{{pmid|36740954}} | | Additionally, it's noteworthy that two MIB-626 trials utilized a twice per day administration regimen. This dosing schedule is significant because it could potentially offer more consistent NAD+ level support throughout the day, although the specific implications of this frequency in relation to circadian rhythms and overall efficacy remain an area for further research.{{pmid|35182418}}{{pmid|36740954}} |
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| ===[[Methyl Donor Deficiency]]===
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| There is a theoretical concern that consuming NMN could deplete [[Methyl Donors|methyl groups]] in the body and might lead to a [[Methyl Donor Deficiency]] associated with symptoms such as low energy and tiredness. NMN is converted to NAD+ in the body, which can then be broken down into nicotinamide. Nicotinamide is then methylated by the liver to form N1-methylnicotinamide, which is excreted in the urine. This methylation process consumes a methyl group from [[S-adenosylmethionine (SAMe)]], the primary methyl donor in the body.
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| For this reason, some individuals who take NMN also supplement with [[Methyl Donors|methyl donors]] such as [[Trimethylglycine (TMG)]] or [[Vitamin B Complex]] to ensure that they are not depleting their body's supply of methyl groups. Some individuals take methyl donors as a precautionary measure, while others may begin supplementation after experiencing sleepiness attributed to NMN.<ref>https://renuebyscience.com/forums/viewtopic.php?t=2575</ref>
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| However, there is no clear evidence yet as clinical trials are lacking. While the biochemical pathway is known, the actual impact of NMN supplementation on the global status of methyl groups is not well-established in humans. It would likely require substantial NMN consumption coupled with an insufficient intake of dietary methyl donors to significantly affect these groups. There could be also a compensatory mechanisms in place slowing down the conversion of NMN to NAD+ or the methylation of nicotinamide if methyl groups were being depleted.
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| ===Risks of NMN Supplementation=== | | ===Risks of NMN Supplementation=== |
