First Study To Measure Postpartum NAD Levels Is Out Now


New moms don’t need scientists to tell them that postpartum is stressful. As if bringing a new life into the world isn’t hard enough, moms have to adjust to an ever-changing body and new identity while keeping their baby happy, healthy, and well-fed.

Despite all that, lactation and breast milk are vastly understudied areas of women’s health. For example, more studies have been published about coffee, wine, and tomatoes than on breast milk or lactation.

Thankfully, a new preclinical study out this week in Cell Reports, brings us closer to understanding which specific kinds of stress postpartum puts on a mother’s body and how NR supplementation might help [1].

Postpartum and metabolic stress: What’s NAD got to do with it?

“New moms don’t need scientists to tell them that postpartum is an episode of metabolic stress,” said Dr. Charles Brenner, professor of biochemistry at the University of Iowa and the principal investigator of the study. “But there has been virtually no scientific investigation into the types of molecular stress that occur during postpartum. During this time, mom’s body becomes reprogrammed to provide for the developing baby. In this study, we found that a key part of this program involves mobilization of NAD and that NR provides amazing support for this process.”

The study, conducted in mice and rats, is the first to measure postpartum NAD levels. The liver, blood, and mammary glands of lactating postpartum mice all showed changes in NAD and its related metabolites. These levels decreased in the livers of postpartum mice and increased in the blood and mammary glands.

Boosting NAD gives metabolically stressed cells a helping hand

Based on their observations, the researchers proposed that the postpartum liver contributes NAD metabolites to other tissues where it is needed to support metabolically demanding activities like milk production.

As cells in the mammary gland get to work, they consume energy to fuel the many metabolic processes involved in creating everything that goes into milk. Previous research has already established a clear connection between NAD, mitochondrial health, and cellular energy production, so it made sense that increasing NAD could help support the activity of this metabolically active tissue.

To test the effects of increasing NAD levels, the researchers started feeding NR to mothers right after giving birth. These NR-supplemented mothers had higher levels of NAD metabolites in all tissues tested, lost more weight, spent more time nursing, and produced nearly twice as much milk as control mothers fed a regular diet.

“The mammary gland is a stressed tissue, and it’s working its little heart out to make all of this material,” said Dr. Bruce German, professor of food science at the University of California, Davis and scientific advisor for the International Milk Genomics Consortium. “It’s an energy-hungry bioreactor, and Dr. Brenner’s results indicate that NR supplementation may support increased production of milk.”

Supporting maternal health benefits offspring, too

NR supplementation not only improved the metabolic health of the mothers but also led to lasting benefits for their offspring. Even though offspring never received NR in their own food, the offspring of NR-supplemented mothers showed greater coordination, strength, and spatial learning ability as adults. For example, in a beam walking test, the offspring of NR-supplemented mothers crossed more quickly and slipped less frequently.

 

Could higher quality milk be the key?

Milk is a complex cocktail of molecules that transcends the deceptively simple label of “food” [2]. In addition to nutrients like fats, protein, vitamins, and minerals, milk contains cells and molecules that help protect babies from disease. It harbors microbes and prebiotics to support a healthy gut. And it contains messages that send cellular signals from mother to child.

Previous research has demonstrated that changes in milk composition can affect how offspring develop and behave. One study of primates showed that increased milk levels of the stress hormone cortisol were associated with more nervous, less confident children [3]. Dr. Brenner’s team reasoned that there had to be a qualitative improvement in the milk to help explain their observations.

For this study, they decided to focus on a molecule called brain-derived neurotrophic growth factor, or BDNF, which helps support the development and survival of neurons. “There’s very little in the literature so far connecting BDNF to milk, but there’s a lot of literature showing that mothers licking their offspring causes them to produce their own BDNF. We had a hunch that maybe the milk itself also had more BDNF,” explained Dr. Brenner.

That hunch paid off. Dr. Brenner’s team found that NR supplementation didn’t just increase milk production, it also changed the composition of the milk itself by increasing levels of BDNF. Dr. Brenner suspects there’s a whole set of bioactive factors that are increased by NR supplementation and plans to continue studying milk quality in his future research.

Groundbreaking work paves the way for future research

“The big question now is: ‘To what extent is this true in human mothers and children?’” says Dr. German. As with all exciting new preclinical research, an important next step is to study safety and efficacy in humans.

NR is a water-soluble vitamin naturally found in trace amounts in cow milk and human breast milk [4, 5]. Multiple clinical trials have demonstrated its ability to safely and effectively increase NAD levels in adults [6–8]. But when it comes to mothers and babies, nothing is more important than safety. More work will be needed to characterize the safety and effects of NR in this special population.

While it’s too soon to say what all of this research means for moms of the non-rodent variety, it opens up an exciting new area for NAD research. It also contributes toward our understanding of lactation and breast milk—areas of women’s health that are woefully understudied.

“Women are often concerned about their milk supply and quality when breastfeeding, so I am super excited to learn of this preclinical information and future potential studies,” says OB-GYN Dr. Alyssa Dweck, assistant clinical professor at Mount Sinai School of Medicine in New York.

Dr. Brenner intends to continue contributing to this area of research. “We’re extremely excited by what we’ve seen NR do during postpartum and what the mom’s NR supplementation does for her offspring,” he says. “We are looking forward to testing these discoveries in people so that we can explore the potential for NR in women’s and family health.”


Charles Brenner, PhD is the Roy J. Carver Chair & Head of Biochemistry and Founding Co-Director the Obesity Research & Education Initiative at the University of Iowa. The discoverer of NR as a vitamin precursor of NAD, he serves as a member of the ChromaDex scientific advisory board and as chief scientific advisor of ChromaDex.

Bruce German, PhD is the John E. Kinsella Endowed Chair in Food, Nutrition and Health, and professor at the Department of Food Science & Technology at the University of California, Davis. He serves as a member of the ChromaDex scientific advisory board.

Alyssa Dweck, MS, MD, FACOG is a practicing gynecologist and ChromaDex spokesperson in Westchester County, New York and Assistant Clinical Professor in the Department of Obstetrics, Gynecology, and Reproductive Science at the Mount Sinai School of Medicine.


References

  1. Ear, P.H. and Chadda A., et al., Maternal nicotinamide riboside enhances postpartum weight loss, juvenile offspring development, and neurogenesis of adult offspring. Cell Rep, 2019.

  2. Andreas, N.J., et al., Human breast milk: A review on its composition and bioactivity. Early Hum Dev, 2015. 91(11): p. 629-635.

  3. Hinde, K., et al., Cortisol in mother’s milk across lactation reflects maternal life history and predicts infant temperament. Behav Ecol, 2014. 26(1): p. 269-281.

  4. Trammell, S.A., et al., Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. J Nutr, 2016. 146(5): p. 957-63.

  5. Ummarino, S., et al., Simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and nicotinamide adenine dinucleotide in milk by a novel enzyme-coupled assay.Food Chem, 2017. 221: p. 161-168.

  6. Trammell, S.A., et al., Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun, 2016. 7: p. 12948.

  7. Martens, C.R., et al., Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults. Nat Commun, 2018. 9(1): p. 1286.

  8. Dollerup, O.L., et al., A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr, 2018.