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NMN/NR and Hormonal Contraceptives: What the Evidence Actually Shows

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At a glance

  • NMN and NR / Oral NAD+ precursors sold as dietary supplements, not FDA-approved drugs [3]
  • Contraceptives covered / Combined pill, Twirla combined patch, NuvaRing combined ring and the Slynd progestin-only pill [2][4][5][6]
  • Label interaction list / Enzyme inducers such as rifampicin, carbamazepine and St. John's wort can lower contraceptive levels [2]
  • What human trials show / NMN and NR raise blood NAD+ in short trials [7][8]
  • Label back-up advice / Back-up contraception for 28 days after stopping an enzyme inducer [2]

Is there a known interaction?

No human drug-interaction study of NMN or NR with any prescription drug, including hormonal contraceptives, has been identified [1]. That means no interaction has been established, not that the pair has been proved safe.

NMN and NR are dietary supplements, not FDA-approved drugs [3]. The Sprintec label says drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease combined oral contraceptive concentrations and potentially diminish effectiveness or increase breakthrough bleeding; named examples include rifampicin, carbamazepine and St. John's wort [2]. NMN and NR are not among the named examples [2]. That is a label-list fact, not a test result.

What does the label say about back-up contraception?

The Sprintec label says no drug-drug interaction studies were conducted with Sprintec [2]. It says to counsel an alternative or back-up method when an enzyme inducer is used, and to continue back-up for 28 days after the inducer is stopped [2]. The Slynd and Twirla labels carry the same CYP3A4 inducer advice [6][4].

What human trials show

Oral NMN and NR raise NAD+ in blood. In a 30-person trial, NMN 250 mg/day for 12 weeks raised whole-blood NAD+, with 15 participants on NMN [7]. In a 2 x 6-week crossover trial of middle-aged and older adults, NR 500 mg twice daily raised NAD+ in blood cells [8]. These trials were small and short, and long-term human safety data are lacking [1].

Which products are covered?

The label facts here cover combined pills (Sprintec), the Twirla combined patch, the NuvaRing combined vaginal ring, and the Slynd progestin-only pill where noted [2][4][5][6]. Other patches, implants, injections and IUDs were not researched.

Frequently asked questions

Can I take NMN with hormonal birth control?
No interaction has been established, and no human study has tested the combination [1]. The combined pill label advises back-up contraception when enzyme inducers such as rifampicin, carbamazepine or St. John's wort are used [2].
Does NMN affect estrogen or contraceptive hormones?
The trials of NMN and NR measured blood NAD+ and safety laboratory values, not contraceptive hormone levels [7][8]. No study measuring contraceptive hormone levels in people taking NMN or NR has been identified [1].
Does NR interact differently from NMN?
No interaction study exists for either [1]. Both are precursors the body converts to NAD+, and the trials of each measured blood NAD+ and safety laboratory values rather than drug levels [9][7][8].
Does the pill affect NMN or NR?
No study has measured NMN or NR levels in pill users [7][8]. Pills containing ethinyl estradiol are known to slow clearance of other substances through CYP1A2: caffeine half-life was 7.88 hours in pill users versus 5.37 hours in controls, and a CYP1A2 marker was 2.8 times higher in pill users in a second study [10][11].

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. Sprintec norgestimate and ethinyl estradiol tablets (Teva) prescribing information. Sprintec norgestimate and ethinyl estradiol tablets (Teva) label
  3. Official web page. Official web page
  4. U.S. National Library of Medicine, DailyMed. Twirla levonorgestrel and ethinyl estradiol transdermal system (Agile) (levonorgestrel/ethinyl estradiol) prescribing information. Twirla levonorgestrel and ethinyl estradiol transdermal system (Agile) (levonorgestrel/ethinyl estradiol) label
  5. U.S. National Library of Medicine, DailyMed. NuvaRing etonogestrel and ethinyl estradiol vaginal ring (Advanz) prescribing information. NuvaRing etonogestrel and ethinyl estradiol vaginal ring (Advanz) label
  6. U.S. National Library of Medicine, DailyMed. Slynd drospirenone tablets (Exeltis) prescribing information. Slynd drospirenone tablets (Exeltis) label
  7. 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
  8. 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
  9. 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
  10. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol. 1985;28(4):425-8. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives
  11. Granfors MT, Backman JT, Laitila J, Neuvonen PJ. Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2. Clin Pharmacol Ther. 2005;78(4):400-11. Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2
Evidence overview for interactions nad nmn: NMN/NR and Hormonal Contraceptives: What the Evidence Actually Shows