NMN (Nicotinamide Mononucleotide)

Growing clinical evidence: published human trials show that oral NMN (250-1,250 mg/day) significantly raises plasma and cellular NAD+ levels over 4-12 weeks without significant adverse effects. Studies by Liao et al. (2022) and Yoshino et al. (2021) show improvements in muscle insulin sensitivity, aerobic physical performance, and ageing markers.

Mechanism and bioavailability debate: NMN is absorbed via the Slc12a8 transporter in the intestine (discovered by Sinclair, 2019), although the magnitude and selectivity of this transport remains subject of scientific debate. A significant fraction of oral NMN is converted to NR (nicotinamide riboside) during first-pass hepatic metabolism before reaching peripheral tissues.

Sublingual vs oral form: sublingual administration bypasses first-pass hepatic metabolism and shows higher bioavailability in some small studies, although the evidence is not conclusive.

Regulatory status: in the US the FDA removed it from the supplement listing in 2022 as it was studied as a medicine. In the EU it has no specific Novel Food approval. In Spain, purchase requires international suppliers or it is obtained through specialised clinics. Typical doses: 250-1,000 mg/day sublingual or in capsules with the first meal; some protocols combine NMN with TMG (trimethylglycine, methyl donor) to avoid methyl group depletion.