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Study · Randomized controlled trial · n = 14 · 2026

6 results

Sublingual NMN administration increases early circulating terminal catabolites 2PY and 4PY compared with oral administration in healthy adult men.

Wakabayashi J, Higashi S, Morifuji M

Scientific reports16 Jun 2026

PMID42304075 (opens in a new tab)PMCIDPMC13534420 (opens in a new tab)DOI10.1038/s41598-026-57552-9 (opens in a new tab)PepBankPUB-42304075
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Summary

Sublingual administration of nicotinamide mononucleotide (NMN) is hypothesized to enhance systemic bioavailability by bypassing hepatic first-pass metabolism, a significant limitation of oral intake. However, direct comparative evidence in humans has been lacking. This study aimed to compare the acute pharmacokinetics of NMN following single-dose oral and sublingual administration in a randomized, two-period crossover trial involving 14 healthy adult males. Participants received NMN via both routes, separated by an 8-day washout period. Blood samples were collected for 60 min post-administration to measure NMN and its metabolites, including nicotinamide (NAM), nicotinamide adenine dinucleotide (NAD⁺), and the terminal catabolites N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3-carboxamide (4PY). The incremental area under the curve (iAUC) was significantly higher for the terminal metabolites 2PY and 4PY following sublingual administration compared to the oral route. In contrast, no significant differences were found for the blood concentrations of NMN, NAM, or NAD⁺ between methods. Both administration routes were well-tolerated, with no adverse events reported. These findings provide the first direct evidence in humans that sublingual administration leads to a more rapid increase in the terminal metabolites (2PY and 4PY) over 0-60 min, although the metabolic origin of these increases could not be distinguished in the present study.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanRandomized controlled trialPharmacokinetics

    In healthy adult men, sublingual NMN increased 2PY iAUC versus oral NMN.

    In plain wordsIn healthy men, sublingual NMN increased 2PY exposure compared with oral NMN.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    Increase2PY iAUC
    Study

    n = 14

    Comparator
    Oral NMN
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated · sublingual · single doseAs given in this study (human).

    Source sentences

    Summary
    The incremental area under the curve (iAUC) was significantly higher for the terminal metabolites 2PY and 4PY following sublingual administration compared to the oral route.
    1 context sentence
    Summary · context
    This study aimed to compare the acute pharmacokinetics of NMN following single-dose oral and sublingual administration in a randomized, two-period crossover trial involving 14 healthy adult males.
  2. 02HumanRandomized controlled trialPharmacokinetics

    In healthy adult men, sublingual NMN increased 4PY iAUC versus oral NMN.

    In plain wordsIn healthy men, sublingual NMN increased 4PY exposure compared with oral NMN.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    Increase4PY iAUC
    Study

    n = 14

    Comparator
    Oral NMN
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated · sublingual · single doseAs given in this study (human).

    Source sentences

    Summary
    The incremental area under the curve (iAUC) was significantly higher for the terminal metabolites 2PY and 4PY following sublingual administration compared to the oral route.
    1 context sentence
    Summary · context
    This study aimed to compare the acute pharmacokinetics of NMN following single-dose oral and sublingual administration in a randomized, two-period crossover trial involving 14 healthy adult males.
  3. 03HumanRandomized controlled trialPharmacokinetics

    In healthy adult men, blood NMN concentrations did not differ significantly between sublingual and oral NMN.

    In plain wordsIn healthy men, blood NMN levels did not differ significantly between sublingual and oral NMN.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    No significant changeBlood NMN concentration
    Study

    n = 14

    Comparator
    Oral NMN
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated · sublingual · single doseAs given in this study (human).

    Source sentences

    Summary
    In contrast, no significant differences were found for the blood concentrations of NMN, NAM, or NAD⁺ between methods.
    1 context sentence
    Summary · context
    This study aimed to compare the acute pharmacokinetics of NMN following single-dose oral and sublingual administration in a randomized, two-period crossover trial involving 14 healthy adult males.
  4. 04HumanRandomized controlled trialPharmacokinetics

    In healthy adult men, blood NAM concentrations did not differ significantly between sublingual and oral NMN.

    In plain wordsIn healthy men, blood NAM levels did not differ significantly between sublingual and oral NMN.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    No significant changeBlood NAM concentration
    Study

    n = 14

    Comparator
    Oral NMN
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated · sublingual · single doseAs given in this study (human).

    Source sentences

    Summary
    In contrast, no significant differences were found for the blood concentrations of NMN, NAM, or NAD⁺ between methods.
    1 context sentence
    Summary · context
    This study aimed to compare the acute pharmacokinetics of NMN following single-dose oral and sublingual administration in a randomized, two-period crossover trial involving 14 healthy adult males.
  5. 05HumanRandomized controlled trialPharmacokinetics

    In healthy adult men, blood NAD⁺ concentrations did not differ significantly between sublingual and oral NMN.

    In plain wordsIn healthy men, blood NAD⁺ levels did not differ significantly between sublingual and oral NMN.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    No significant changeBlood NAD⁺ concentration
    Study

    n = 14

    Comparator
    Oral NMN
    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated · sublingual · single doseAs given in this study (human).

    Source sentences

    Summary
    In contrast, no significant differences were found for the blood concentrations of NMN, NAM, or NAD⁺ between methods.
    1 context sentence
    Summary · context
    This study aimed to compare the acute pharmacokinetics of NMN following single-dose oral and sublingual administration in a randomized, two-period crossover trial involving 14 healthy adult males.
  6. 06HumanRandomized controlled trialSafety outcome

    In healthy adult men, both NMN administration routes were well tolerated, with no reported adverse events.

    In plain wordsIn healthy men, oral and sublingual NMN caused no reported adverse events.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    Not applicableAdverse events
    Study

    n = 14

    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated · oral and sublingual · single doseAs given in this study (human).

    Source sentences

    Summary
    Both administration routes were well-tolerated, with no adverse events reported.
    1 context sentence
    Summary · context
    This study aimed to compare the acute pharmacokinetics of NMN following single-dose oral and sublingual administration in a randomized, two-period crossover trial involving 14 healthy adult males.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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