No published human clinical study has evaluated the safety of NAD+ or its precursors, including NR, NMN, or high doses of niacin or nicotinamide, during pregnancy or breastfeeding.
Due to the lack of such safety data — rather than because there is specific evidence indicating that these compounds are harmful — the most appropriate conclusion is that NAD+ supplementation should not be started or continued during pregnancy or breastfeeding without prior consultation with an obstetrician, midwife or other qualified healthcare professional.
In this article, we explain what is currently known, what is still unknown, and why medical consultation is particularly important in this situation.
What is actually known about the safety of NAD+ in pregnancy?
The most important starting point is that no randomised, placebo-controlled human trial has evaluated the safety of NR, NMN or any other NAD+ precursor supplement during pregnancy.
The key human studies discussed in our other guides regarding NAD+ were conducted in non-pregnant adults. Pregnancy is routinely used as an exclusion criterion in clinical trials of this type.
Another issue was investigated, however: what happens when normal NAD+ biosynthesis is disrupted during pregnancy.
One important study identified genetic mutations that disrupt the natural pathway for producing NAD+ from tryptophan, known as the de novo synthesis pathway. In affected families, these disorders were associated with numerous congenital defects, including those of the heart, spine, and kidneys [1].
The same study also used a mouse model with a similar NAD+ biosynthesis disorder. In this model, supplementation with niacin, a dietary precursor of NAD+ and a form of vitamin B3, prevented birth defects associated with the deficiency state [1].
Related animal studies have also shown that NAD+ deficiency resulting from a combination of genetic and environmental factors can contribute to birth defects and pregnancy loss in mice [2].
These results are significant, but require careful interpretation.
They demonstrate that proper NAD+ metabolism is important during pregnancy and foetal development. They also support the importance of an adequate intake of vitamin B3 as part of a balanced diet.
However, they do not prove that concentrated or high-dose NAD+ precursor supplements are safe during human pregnancy.
Correcting a nutritional or metabolic deficiency is not the same as supplementing beyond normal physiological requirements.
So the question „is adequate vitamin B3 intake important during pregnancy?” is entirely different from the question „have high doses of NAD+ precursors been studied and found to be safe during pregnancy in humans?”.
The first of these statements is supported by data from the fields of nutrition and developmental biology. The second has not been established.
For this reason, results from animal studies showing that niacin can correct a specific NAD+ deficiency state should not be interpreted as evidence that high doses of NR, NMN or other NAD+-related products are safe during pregnancy.
Why is there a research gap?
The lack of NAD+ studies conducted specifically in pregnant women is not unusual.
Pregnant people are often excluded from early-phase clinical trials concerning new medicines, supplements or other biologically active compounds.
This is primarily due to ethical and regulatory reasons.
An insufficiently researched intervention could potentially affect foetal development, which is why researchers usually avoid deliberately exposing pregnant individuals to compounds that do not yet have a sufficiently established safety history.
Even after a given compound has been extensively studied in non-pregnant adults, research conducted specifically in pregnancy requires additional ethical assessment, careful monitoring and appropriately designed protocols.
Research into NAD+ precursors is still a relatively young field.
Most human studies regarding compounds such as NR and NMN have been published within the last few years, with a significant portion of them focusing on short-term safety, biomarkers, metabolism, ageing-related biology, and specific populations with diseases.
The evidence base is therefore not yet at the stage of development where dedicated safety studies in pregnancy would usually be expected.
The current lack of pregnancy data should therefore not be automatically interpreted as evidence of harm.
However, it should not be treated as proof of safety either.
The most appropriate conclusion is simply that the safety of using concentrated NAD+ precursors during pregnancy in humans remains unknown.
Breastfeeding issues
The evidentiary gap regarding breastfeeding is similarly large.
No published human study has determined whether NR, NMN, NAD+ or their major metabolites pass into human breast milk.
There are also no reliable data in humans showing what concentrations could appear in milk following supplementation, nor what exposure a breastfed infant could be subjected to.
Without this data, it is not possible to accurately estimate the child's exposure.
This is important because an infant's body weight is significantly lower than that of an adult, and their metabolism, renal function, liver function, and stage of development are also different.
It cannot therefore be assumed that a dose or exposure well tolerated by adults will have the same safety profile in an infant.
It is also unknown whether metabolites formed following supplementation with NR, NMN, or other NAD+-related compounds could have a clinically relevant effect on a breastfed infant.
Absence of evidence does not mean evidence of harm has been shown.
This means that relevant safety issues have not been sufficiently investigated.
For this reason, breastfeeding should also be regarded as a situation where general safety data from studies in adults cannot be directly applied.
Why is „consult a doctor” actually the right answer here?
In this context, the recommendation to consult a healthcare professional is not merely a standard disclaimer.
It reflects the main limitation of the available evidence.
At the same time, two important facts exist.
Firstly, NAD+ metabolism is biologically important during pregnancy and foetal development. Research into genetic and metabolic NAD+ deficiencies has shown that disruption of this pathway can have severe developmental consequences [1,2].
Secondly, there are no clinical safety data in humans to determine the effect of concentrated NAD+ precursor supplementation during pregnancy or breastfeeding.
This combination makes an individual medical assessment particularly important.
The fact that a given biological pathway is important does not automatically mean that further modifying it is safe.
A lack of safety data in pregnancy also means that results obtained in healthy, non-pregnant adults cannot be reliably used to answer questions regarding foetal development or infant exposure during breastfeeding.
A healthcare professional who knows the course of the pregnancy, diet, medical history, medications used, laboratory test results and individual risk factors can better assess whether additional supplementation is appropriate.
This is of particular importance because nutritional requirements during pregnancy differ from those of the general adult population, and standard antenatal care already includes specific recommendations for vitamins and minerals.
If someone is pregnant, planning a pregnancy or breastfeeding and is considering using a NAD+ precursor supplement, the appropriate next step is to discuss this with an obstetrician, midwife, pharmacist or other qualified prenatal care specialist before starting or continuing to use the product.
General safety data for NR, NMN or NAD+ in adults should not be taken as a substitute for individual medical advice regarding pregnancy.
Limitations of current evidence
- No published clinical study involving humans has evaluated the safety of NR, NMN, NAD+, or high-dose niacin or nicotinamide supplementation specifically during pregnancy.
- No published human clinical trial has confirmed the safety of these compounds during breastfeeding.
- Most available human studies on NAD+ precursors exclude pregnant people, therefore general safety results in adults cannot be considered applicable to pregnancy.
- Research linking NAD+ deficiency to congenital defects concerns genetic or environmental deficiency states, rather than the safety of supplementation exceeding normal physiological requirements [1,2].
- Animal study results showing that niacin can correct developmental disorders associated with NAD+ deficiency in specific models do not prove that high-dose supplementation with NAD+ precursors is safe during a normal human pregnancy.
- There is a lack of reliable human data determining whether NR, NMN, NAD+ or their key metabolites pass into human breast milk.
- There is a lack of reliable data determining the degree of infant exposure during breastfeeding following maternal supplementation with NAD+ precursors.
- The impact of long-term maternal supplementation on foetal development, the course of pregnancy, infant development and the safety of breastfeeding remains unknown.
- The absence of documented harm should not be interpreted as proof of safety when appropriate clinical trials in pregnancy have not been conducted.
Disclaimer
The article is strictly for educational purposes and summarises scientific research. It does not constitute medical, obstetrical, paediatric or breastfeeding advice.
Current evidence does not allow us to state whether NAD+, NR, NMN or high-dose supplements of niacin or nicotinamide are safe or unsafe during pregnancy or breastfeeding. Above all, this reflects a lack of adequate safety studies in humans within these populations.
NAD+ and its precursors should not be presented as FDA- or EMA-approved treatments for issues related to pregnancy, foetal development, breastfeeding, or for any other medical purposes, unless referring to a specific approved medicinal product and indication.
Adequate intake of vitamin B3 is a recognised element of proper nutrition, including during pregnancy, but proper dietary requirements should not be equated with the use of concentrated or high-dose supplements of NAD+ precursors.
Do not start, continue, significantly increase or stop taking the supplement during pregnancy or breastfeeding without first consulting an obstetrician, midwife, pharmacist or other suitably qualified healthcare professional.
Questions regarding individual vitamin B3 requirements, prenatal supplements, nutritional deficiencies or NAD+-related products during pregnancy or breastfeeding should be discussed with the healthcare professional responsible for your prenatal or postnatal care.
References
[1] Shi, H., Enriquez, A., Rapadas, M., Martin, E. M. M. A., Wang, R., Moreau, J., Lim, C. K., Szot, J. O., Ip, E., Hughes, J. N., Sugimoto, K., Humphreys, D. T., McInerney-Leo, A. M., Leo, P. J., Maghzal, G. J., Halliday, J., Smith, J., Colley, A., Mark, P. R., Collins, F., Sillence, D. O., Winlaw, D. S., Ho, J. W. K., Guillemin, G. J., Brown, M. A., Kikuchi, K., Thomas, P. Q., Stocker, R., Giannoulatou, E., Chapman, G., Duncan, E. L., Sparrow, D. B., & Dunwoodie, S. L. (2017). NAD deficiency, congenital malformations, and niacin supplementation. New England Journal of Medicine, 377(6), 544–552. https://doi.org/10.1056/NEJMoa1616361
[2] Cuny, H., Rapadas, M., Gereis, J., Martin, E. M. M. A., Kirk, R. B., Shi, H., & Dunwoodie, S. L. (2020). NAD deficiency due to environmental factors or gene-environment interactions causes congenital malformations and miscarriage in mice. Proceedings of the National Academy of Sciences, 117(7), 3738–3747. https://doi.org/10.1073/pnas.1916588117