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NMN/NR and PPIs (Omeprazole, Pantoprazole): Interaction Guide

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At a glance

  • Human interaction studies / None found for NMN or NR with any prescription drug [1]
  • Nexium label coverage / NMN and NR are not named in its interaction section [2]
  • Only plausible mechanism / PPIs lower stomach acid and can reduce absorption of acid-dependent drugs [2]
  • Effect on NMN or NR blood levels / No study found
  • Dose spacing / No study found
  • Supplement status / Oral dietary supplements, not FDA-approved drugs [3]
  • Long-term PPI label warnings / Vitamin B12 malabsorption and rare low magnesium [2]

What are these two products?

NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are oral dietary supplements that the body converts to NAD+, a coenzyme in cellular energy metabolism [3][4]. Neither is an FDA-approved drug, and no NAD+ precursor is approved to treat aging or any disease [3]. Oral NMN 250 mg daily for 12 weeks raised whole-blood NAD+ in 30 healthy adults [5], and NR 1,000 mg daily for 6 weeks raised PBMC NAD+ about 60% over placebo in 24 adults aged 55 to 79 [6].

Omeprazole, pantoprazole and esomeprazole are prescription proton pump inhibitors that block the parietal cell H+/K+ ATPase [2].

Could a PPI change NMN or NR absorption?

The Nexium label says esomeprazole can reduce absorption of other drugs by lowering intragastric acidity, and names iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, and ketoconazole or itraconazole as examples [2]. For mycophenolate mofetil, omeprazole 20 mg twice daily for 4 days lowered mycophenolic acid peak concentration 52% and total exposure 23% in 12 healthy subjects [2]. Whether oral NMN or NR is absorbed that way in someone taking a PPI has not been studied.

What the Nexium label does list

Its interaction section covers antiretrovirals (rilpivirine-containing products are contraindicated), warfarin, methotrexate, CYP2C19 substrates such as clopidogrel, citalopram and cilostazol, digoxin, tacrolimus, drugs dependent on gastric pH for absorption, and several diagnostic tests [2]. Across the PPI labels, rilpivirine is the only drug-interaction contraindication [2]. PPIs also differ on clopidogrel: the omeprazole and Nexium labels say to avoid the combination, while pantoprazole 80 mg lowered clopidogrel active-metabolite exposure about 14%, which its label calls not clinically important [2].

What long-term PPI use carries

These are PPI label warnings and observational associations, not findings about NAD+ precursors. The labels say daily acid suppression over a long period, for example longer than 3 years, may cause vitamin B12 malabsorption, and they call reported deficiency rare [2]. In an observational case-control study of 25,956 adults with new B12 deficiency and 184,199 controls, two or more years of PPI supply was associated with an odds ratio of 1.65 (95% CI 1.58 to 1.73), which shows an association rather than proof of cause [7]. The labels describe hypomagnesemia as rare, reported in patients treated for at least 3 months and mostly after a year, and say clinicians may check magnesium before and periodically during prolonged treatment [2].

Frequently asked questions

Does the Nexium label list NMN or NR?
No. Its drug interactions section names antiretrovirals, warfarin, methotrexate, CYP2C19 substrates, digoxin, tacrolimus, drugs that need stomach acid for absorption, and diagnostic tests [2].
Which drugs does the Nexium label say need stomach acid?
Iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, and ketoconazole or itraconazole are the examples the label gives for reduced absorption from lower intragastric acidity [2].
Do PPIs change how well NMN or NR raise NAD+?
No study has tested this. Oral NMN and NR raised blood NAD+ in trials in healthy adults [5][6], but no interaction study with prescription drugs, including PPIs, was found [1].
What do PPI labels flag with long-term use?
The labels flag vitamin B12 malabsorption with long use, for example longer than 3 years, and rare hypomagnesemia reported after at least 3 months and mostly after a year, with magnesium checks possible before and during prolonged treatment [2]. An observational case-control study found an odds ratio of 1.65 for B12 deficiency with two or more years of PPI supply [7].
Are NMN and NR FDA-approved drugs?
No. Both are sold in the US as oral dietary supplements, and no NAD+ precursor product is FDA-approved to treat aging or any disease [3].

References

  1. Freeberg KA, Udovich CC, Martens CR, Seals DR, Craighead DH. Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions. J Gerontol A Biol Sci Med Sci. 2023;78(12):2435-2448. Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions
  2. U.S. National Library of Medicine, DailyMed. Nexium (esomeprazole magnesium) prescribing information. Nexium (esomeprazole magnesium) label
  3. Official web page. Official web page
  4. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
  5. Okabe K, Yaku K, Uchida Y, Fukamizu Y, Sato T, Sakurai T, et al. Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Front Nutr. 2022;9:868640. Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects
  6. Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
  7. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency
Evidence overview for interactions nad nmn: NMN/NR and PPIs (Omeprazole, Pantoprazole): Interaction Guide