Opposite effects of NAM and Melatonin

This paper suggests that Nicotinamide increases oxidative stress, but also increases expression of SAHH (AHCY), while melatonin does the opposite - reduces the expression of SAHH.

  1. Results showed that NAM (20 mM) administration during in vitro maturation (IVM) significantly reduced oocyte maturation and actin distribution, while induced reactive oxygen species (ROS) accumulation and mitochondrial dysfunction
  1. Inspecting the underlying mechanisms behind NAM-associated toxicity revealed an increase in transcription pattern of NAM methylation (NNMT and AHCY) genes in NAM-treated oocytes while the opposite profile was observed upon melatonin supplementation (R1)

This could be related to negative symptoms that some people experience from Melatonin (nightmares, psychosis) - if poorly functioning AHCY (SAHH) gets inhibited even more leading to increased SAH and lowered cysteine synthesis.

NAM apparently has dose dependent effect: small doses have positive effect, while high doses lead to negative effects. Another paper:

Our results showed that low NAM concentrations reduced the oxidative stress and improved mitochondrial profile, total cleavage and 8-16 cell stage embryo development whereas the opposite profile was observed upon exposure to high NAM concentrations (10 mM onward) (R2)

References

1
Melatonin Alleviates the Toxicity of High Nicotinamide Concentrations in Oocytes: Potential Interaction with Nicotinamide Methylation Signaling
2021
2
Nicotinamide Supplementation during the In Vitro Maturation of Oocytes Improves the Developmental Competence of Preimplantation Embryos: Potential Link to SIRT1/AKT Signaling
2020