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Supplementation to increase NAD+ in lactating mice results in healthy, stronger, smarter offspring


This study fed lactating mice Nicotinamide Riboside (NR) in chow for 21 days after birth of offspring to measure the effect on the health of their pups who did not receive any NR.

After 21 days, the pups were removed from the mothers and fed normal chow.

Surprisingly, the offspring whose mothers received NR exhibited:

  • Higher body weight
  • Increased activity
  • Larger brain size
  • Diminished Anxiety
  • improved spatial memory

These improvements in health and behavior persisted for the length of the study, which was 90 days after birth. Some quotes from the study:

adding NR to normal chow (NC) solely in the 21 days in which new mouse and rat mothers are co-housed with pups produces a series of profound effects on maternal metabolism and juvenile development, which result in persistent physical, neurobehavioral, and neurodevelopmental advantages to the adult offspring of NR-supplemented mothers

Offspring of NR-supplemented mothers have multiple behavioral advantages, which include decreased anxiety-like behavior, resistance to the onset of behavioral immobility, improved spatial memory, and enhanced motor learning and performance

a new mother’s metabolism and maternal functions can be enhanced by increasing her systemic NAD synthesis, thereby conferring long-lasting advantages to her offspring.

Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring

 

Liver NAD+ decreases in lactating females – NR restores liver NAD+

14 days after giving birth, NAD+ in liver is significantly lower in nursing mothers than in control mice.

Supplementing with NR allowed nursing mothers to increase their liver NAD+ and other metabolites

NR not found in blood, but NAD+ in blood increased

 

Once again, NR was not found in blood of the test subjects.

However supplementation with NR resulted in higher levels of  NAD+ and other metabolites in the blood of lactating females

Massive increase of NAD+ in milk when lactating

The increase of NAD+ levels in mammary glands of lactating vs non-lactating females is quite eye-opening, and demonstrates the importance of NAD+ to the offspring.

Supplementing with NR further increased the NAD+ levels in milk from lactating females.

NR supplementation results in increased milk for offspring

At days 7, 14, and 21, the mother mice were given oxytocin to help induce milk gathering.

Day 14 is around the peak lactation time for this breed of mice, and you can see that the quantity of milk collected in mice given NR was more  than 2x that of control mice a that time point.

NMN found at 20x greater levels than NR in milk

NR supplementation increased levels of NR, NMN, and NAD+ found in lactating females milk.

Strikingly, NMN was found at 20x higher quantities than NR (20 pmol/mg vs 1 pmol/mg).

Supplementation with NR elevated NR levels found in milk 5x.

Levels of NMN were also elevated in milk after supplementation with NR

 

No NR found intact in milk

Although small quantities of NR are found in the milk of lactating females as shown in charts above, none was found to be directly from the NR supplements.

A heavy atom was added to the  NAM and ribose moieties of NR molecules, and the compound was introduced by gavage to lactating mice at day 13. At 2–24 h post-gavage, mice were milked.

As shown in chart G, small quantities of NR were found in milk of lactating females.

Single labelled NAM was prevalent for up to 14 hours. However, no double-labeled NR was ever detected.  

This agrees with the Liu study that finds all NR was degraded to NAM in the GI tract or liver, before being reconstituted as NR in the milk

the mother’s oral NR is not directly transmitted to her milk

Conclusion

This research shows NAD+ in mothers milk is critical for optimum development of the offspring.

NAD+ levels decrease in the liver, but increase 10x in  milk of lactating females, to supply the offspring.

Oral supplementation of NR is not able to make its way directly to mothers milk, but by increasing levels of NAD+ in the liver it is able to influence NAD+ levels in milk of lactating female mice, resulting in healthier offspring.

NMN was 20x more prevalent than NR in milk of control animals.  After supplementing with NR, NMN also increased and found to be  5 x more prevalent than NR.

Supplementation to increase NAD+ levels in nursing mothers results in healthier, stronger, and smarter offspring.

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