Researchers at the University of Iowa have found that giving mouse mothers a dietary supplement called nicotinamide riboside (NR) while they are nursing has both physical and behavioral benefits for their pups that last into adulthood. The studies, described in Cell Reports, also showed that NR-supplemented nursing mice also lost weight more quickly and produced more milk than those that didn’t receive the extra dietary boost.
The researchers, headed by Charles Brenner, PhD, a University of Iowa professor and head of biochemistry at the University of Iowa Carver College of Medicine, acknowledged that it is not yet known whether the same supplement can safely benefit breastfeeding women and their infants. “Improving the mom’s micronutrition with NR supplementation increased the quantity and quality of her milk, and the effects on the offspring were apparent from the day the mouse pups opened their eyes and started to move around,” Brenner commented. “Now we want to know if NR can safely increase lactation in women and if taking NR increases the levels of bioactive factors in human milk like it does in mice and rats.” The team reported its findings in a paper titled, “Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring.”
Nicotinamide adenine dinucleotide (NAD) and related co-enzymes are central to just about all metabolic processes, but are disrupted during periods of metabolic stress, the authors explained. NR is a form of vitamin B3 that studies in humans and animals have shown can boost circulating levels of NAD during metabolic stress. “The common theme that unites models in which NR has provided efficacy is that the NAD metabolome, particularly levels of NAD+ and/or NADPH, is dysregulated by particular types of metabolic stress,” the researchers commented. NR is already sold widely as a dietary supplement, and is also being tested in human diseases.
The period just after giving birth, and during lactation, is a time that involves major metabolic changes and metabolic stress to the mother. “Postpartum constitutes an understudied episode of metabolic stress in which a new mother experiences a storm of hormonal alterations and sleep disruption, while her pituitary, liver, and mammary become programmed for lactation, and she undertakes the physical and emotional caretaking of her offspring,” the team stated. The mother’s health also impacts on the quality and quantity of milk produced, and so on neonatal health, which can then affect the pup’s development.
The University of Iowa team’s studies found that during the postpartum period there is a dramatic diversion of NAD metabolites from the liver to the mammary glands. Levels in the liver are cut almost in half and levels of NAD metabolites increase more than 20-fold in the mammary tissue. This shift plays a crucial role in promoting milk production. NR-supplementation in mice returned liver levels of NAD back to or above normal.
Their studies also showed that giving oral NR supplements to mouse mothers from birth to weaning results in “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.”
Mothers given the oral NR supplement exhibited enhanced nursing behavior, and exhibited increased prolactin expression in the pituitary and so increased milk production. Pups feeding from mothers given oral NR were larger at weaning than those of control mothers, and had better glycemic control. They also put on more lean muscle and less fat as adults. “Whereas mice raised by NR-supplemented mothers had greater lean and fat mass at weaning, as 90-day-old adults, the same animals had less fat while preserving their lean mass,” the authors stated.
Interestingly, levels of brain-derived neurotrophic factor (BDNF) were increased in the milk of NR-supplemented nursing mothers. BDNF is a growth factor that is important for juvenile brain development, the authors pointed out. Pups feeding from these mothers demonstrated higher levels of BDNF in their brains, and advanced brain developments, while the adult offspring demonstrated increased neurogenesis compared with the offspring of control mothers. “The powerful effects of BDNF on development, learning, and protection against psychological imbalances are well known,” the authors pointed out.
Pups of NR-supplemented mothers also exhibited neurobehavioral benefits that were evident well past weaning, the team commented. For example, behavioral tests showed that pups of the mothers given NR were tended to be more active and adventurous while they were still nursing and also when they grew into adults. “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,” the team wrote. These benefits were evident in 15-day-old pups and persisted into adulthood.
The authors suggest that their results could springboard clinical studies to see whether NR supplementation might boost lactation and post-partum weight loss in women. Human studies could also investigate whether NR might increase levels of bioactive substances such as BDNF in human milk, and even potentially improve childhood and adult development. “We are really excited to test whether NR will improve lactation in women and whether it will have some of these exciting secondary outcomes, like increasing maternal weight loss and potentially improving childhood development,” Brenner concluded.