Mechanism of Action and Target Biology NNMT Enzyme and Function: Nicotinamide N-methyltransferase (NNMT) catalyzes the SAM-dependent methylation of nicotinamide: Reaction: Nicotinamide + SAM 1-methylnicotinamide (1-MNA) + S-adenosylhomocysteine (SAH) Expression: Liver, adipose tissue (particularly visceral), smooth muscle, some neurons Regulation: Increased expression in obesity, diabetes, aging, certain cancers Substrates consumed: Nicotinamide (NAD+ precursor) and SAM (methyl donor) 5-Amino-1MQ Inhibition Mechanism: Competitive inhibitor with respect to nicotinamide substrate IC: Submicromolar range for NNMT enzyme Selectivity: Minimal inhibition of other methyltransferases at relevant concentrations Result: Increased intracellular nicotinamide availability for NAD+ salvage pathway Downstream Effects of NNMT Inhibition: 1
Ying W, Riopel M, Bandyopadhyay G et al (2017) Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity
No controlled human trials have studied the combination
This allows for efficient and rapid delivery of the vitamin into the bloodstream, ensuring optimal levels
Comparing Injections with Tablets While B12 tablets can suffice for the general population, injections are crucial for those with severe absorption issues
Inositol Inositol breaks down fats to keep them from accumulating