Most people find this to be uncomfortable, but not unbearable, and it dramatically impacts the results you get - so its a tradeoff most people are willing to make
Burtscher J, Syed MMK, Lashuel HA, Millet GP
Additionally, the observation that changes in symptoms as assessed by PainDetect are correlated with changes in the CNFD in the ARA 290 treatment group alone, further support a functional relationship between small fiber density and neuropathic symptoms
10.1038/cddis.2011.11 Cell Death Dis
In animal-model work, NNMT inhibition with 5-Amino-1MQ has been associated with changes in adipose-tissue mass, in NAD+ pool sizes (because NNMT consumes nicotinamide that would otherwise feed the NAD+ salvage pathway), and in methyl-donor dynamics (because NNMT consumes S-adenosylmethionine)