Overview of NAD metabolism in interaction with methyl-group metabolism.
PD, SAH, SAH S-adenosyl homocysteine
The figure shows various routes of NAD biosynthesis, and examples of NAD degradation leading to Nam production. If not recycled, Nam is methylated to Me-Nam, in a reaction catalyzed by NNMT and requiring SAM as methyl-group donor. The other product of this reaction, SAH, is further converted to HCy, and subsequently regenerated to methionine in the methionine cycle. Me-Nam 1-methyl nicotinamide, NAAD Nicotinic acid adenine dinucleotide, Nam Nicotinamide, Nam N-oxide Nicotinamide N-oxide, cADPR Cyclic ADP-ribose, ADPR Adenosine diphosphate ribose, NAR Nicotinic acid ribonucleoside, NR Nicotinamide riboside, NMN, Nicotinamide mononucleotide, NA Nicotinic acid, Me-2-PY N1-methyl-2-pyridone-5-carboxamide, Me-4-PY N-methyl-4-pyridone-5-carboxamide, NAMN Nicotinic acid mononucleotide, SAM S-adenosyl methionine, SAH S-adenosyl homocysteine, NNMT Nicotinamide N-methyltransferase, MS Methionine synthase, CD38 Cluster of differentiation 38/cyclic ADP-ribose hydrolase, Methyl-THF Methyl-tetrahydrofolate, THF Tetrahydrofolate, BHMT, Betaine homocysteine methyltransferase, Di-Gly Dimethyl glycine, Bet Betaine.It has also been reported that NR treatment at lower doses, alone or in combination with pterostilbene, may be associated with a mild increase in triglycerides, total cholesterol and LDLOur study has several limitations. The results are based on a 4-week trial period and thus not informative with regard to long-term safety of 3000 mg NR daily. Therefore, until this is established, we strongly discourage the use of this dose outside of clinical studies with appropriate safety monitoring. Nevertheless, our results are sufficient to enable further testing of this dose in upcoming phase II clinical trials. The female to male ratio in our study, with only 3 and 2 females included per arm, was lower than that observed in the general PD population