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The legalization of cannabis in the United States has led to more widespread use, including among women of reproductive age [1, 2]. The CDC has taken a conservative approach and currently advises breastfeeding women to reduce or avoid cannabis use to limit the potential risk to infants; however, this guideline is rooted in little scientific evidence [3, 4].

“For most of our lives, cannabis has been illegal,” says Michelle (Shelley) McGuire, director of the Margaret Ritchie School of Family and Consumer Sciences and a professor in the College of Agricultural and Life Sciences at the University of Idaho. There’s “shockingly little data” on how cannabis affects the composition of breast milk.

“Parents really want that information,” says Courtney Meehan, a professor and interim dean for the College of Arts and Sciences at Washington State University. “The cannabis research world is new, and we’re playing catch-up.” 

In a new prospective study, published in Breastfeeding Medicine, Meehan, McGuire, and colleagues show that in breastfeeding individuals who frequently use cannabis, delta-9-tetrahydrocannibinol (THC), the primary psychoactive compound, is detected in human milk [5]. 

Breastfeeding mothers were asked to abstain from cannabis for 12 hours prior to the milk sample collection. After the abstention, participants collected a milk sample and were free to administer their own cannabis [5]. Due to ethical considerations, the research team did not provide the cannabis products to participants. 

Participants were asked to collect full breast expression samples, meaning they expressed until there was no more milk [5]. This was particularly important as milk fat increases at the end of a feed, and THC is fat-soluble. Previous studies had not done this [3, 4].

The researchers confirmed that THC can be measured in human milk following abstention and after single and repeated cannabis use. After single cannabis use, the time at which THC levels peaked was highly variable, ranging from 30 minutes to 1.25 hours [5]. 

“This was surprising to us,” Meehan says. “It shows us that there are so many other variables that we can’t identify that might be contributing to that variation. In the future, understanding those variables is going to be really important.” 

The researchers also found that THC concentrations in human milk increased when cannabis was used more frequently [5]. 

The data suggest that cannabis is distinct from alcohol, which has been shown to peak in human milk 30-60 minutes after consuming an alcoholic beverage [6].

“There is an assumption among some cannabis users that alcohol and cannabis will behave the same and that individuals who use cannabis can predict the timing of its peak and decline in human milk,” says Meehan.

The researchers estimated that an infant would consume a median of 0.0052 mg/kg of body weight of THC in a single feed [5]. It is not known if there are any impacts on the nursing baby. The lowest level of THC in milk that has been observed to have an adverse effect is 0.036 mg/kg of body weight [7]. 

“We know nothing about the potential effects on babies. Zero,” says McGuire. “A lot of things show up in milk and have no effect on the baby. The proof is going to be in the pudding. Until then, we can say nothing.” 

But the research looking at short- and long-term effects on developing infants has been slow. According to Meehan and McGuire, one of the reasons is that breastfeeding women have historically been excluded, forgotten, and under-studied.

McGuire says, “It’s a systemic problem, especially considering how important breast milk is for the baby’s development.” 

Indeed, human milk is considered the “gold standard” for infant nutrition due to its positive effects on early neurodevelopment and the immune system. Therefore, future studies looking at the effects of cannabis use on infant development are critical. 

Moreover, cannabis use among postpartum women has significantly increased in states that have legalized it [2]. In a related study published earlier this year, Meehan, McGuire, and colleagues show that many nursing women are using cannabis products, not for recreation, but to treat or manage health conditions, usually related to mental health [8]. 

“Women are not passively making the decision (to use cannabis),” says Meehan. “They are actively seeking out information and actively weighing the costs and benefits of doing this. These women are working hard to make the best decisions based on the available information that they can find.” 

Meehan adds that when conducting these studies, “It’s critical for us that we avoid stigmatizing women.

“We’re scientists here — completely agnostic with no value judgment,” says McGuire. “We just feel like women need evidence-based information.”

References

1. Alshaarawy O, Anthony JC. Cannabis use among women of reproductive age in the United States: 2002-2017. Addict Behav. 2019 Dec;99:106082.
2. Skelton KR, Hecht AA, Benjamin-Neelon SE. Association of recreational cannabis legalization with maternal cannabis use in the preconception, prenatal, and postpartum periods. JAMA Netw Open. 2021 Feb 1;4(2):e210138.
3. Bertrand KA, Hanan NJ, Honerkamp-Smith G, Best BM, Chambers CD. Marijuana use by breastfeeding mothers and cannabinoid concentrations in breast milk. Pediatrics. 2018 Sep;142(3).
4. Wymore EM, Palmer C, Wang GS, Metz TD, Bourne DWA, Sempio C, et al. Persistence of Δ-9-tetrahydrocannabinol in human breast milk. JAMA Pediatr. 2021 Jun 1;175(6):632-4.
5. Holdsworth EA, Berim A, Gang DR, Williams JE, Smith CB, Caffé B, et al. Human milk cannabinoid concentrations and associations with maternal factors: The lactation and cannabis (lac) study. Breastfeed Med. 2024 Jul;19(7):515-24.
6. Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development. 2006– [cited August 2, 2024]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501469/.
7. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain). Scientific opinion on the risks for human health related to the presence of tetrahydrocannabinol (thc) in milk and other food of animal origin. EFSA Journal. 2015;13(6):4141.
8. Smith CB, Schmidt J, Holdsworth EA, Caffe B, Brooks O, Williams JE, et al. Cannabis use, decision making, and perceptions of risk among breastfeeding individuals: The lactation and cannabis (lac) study. J Cannabis Res. 2024 Feb 16;6(1):6.

A newly discovered brain hormone called CCN3 ramps up in postpartum lactating mothers to promote bone formation and keep bones strong, reports a new study in mice (1). The findings may explain how mammals prevent bone breakdown after giving birth as their bodies siphon calcium from their bones and use it to produce milk for their infants, says Holly Ingraham, a cellular and molecular pharmacologist at the University of California, San Francisco, who led the work. According to Ingraham, the discovery of CCN3 may also point to new ways of treating osteoporosis, bone fractures, or other conditions. 

Estrogen is a well-known bone builder. That’s why in menopause, when estrogen levels drop, women become especially prone to osteoporosis and fractures. But estrogen drops sharply at another time in a woman’s life, too—the postpartum period. After surging during the end of pregnancy, estradiol, the main form of estrogen in women of reproductive age, falls during lactation. Female rodents (2), macaque monkeys (3) and humans (4) experience a high level of bone loss and bone turnover as calcium from maternal bones is redirected toward milk production. 

“It really made sense that mother nature would come up with a way to regenerate bone during this period, so that the body can strip away bone and not have the mother disintegrate into jelly,” Ingraham says. 

Ingraham’s team stumbled onto CCN3’s bone-building role when they found that deleting estrogen receptors from specific neurons in the arcuate nucleus, a region of the hypothalamus, counterintuitively caused female mice to grow extra strong and massive bones (5). “We had to figure out how this extraordinary bone phenotype came about,” she says. 

The researchers suspected that this bone-building effect was switched on by a molecule circulating in the blood. They homed in on a molecule they had identified earlier by looking at changes in gene expression in the neurons engineered to lack estrogen receptors. That molecule turned out to be CCN3, which stands for cellular communication network factor 3. Further experiments revealed that when mice began lactating, CCN3 levels rose. “There was a 100% correlation with when the phenotype came on,” Ingraham said. When they weaned their young, CCN3 dipped back down.

When Ingraham and her colleagues blocked the hormone before mice got pregnant, their bones degenerated during pregnancy, and their offspring grew poorly.  Additionally, when the hormone was boosted in the blood of mice that were not lactating, “then you start building up bone strength in both males and females, young and old,” she says. 

Some researchers have argued that there must be an off switch to this mechanism, but Ingraham argues that the body may not need one. She and her colleagues instead posit that a signal that travels to the brain to put CCN3 into high gear. Then, after lactation, estrogen levels resume, bringing the body’s usual bone-building mechanism back online. CCN3 gets dialed down but still remains at low levels during the transition. “The brain integrates all these signals to decide what to do—especially in female physiology,” she says. 

The researchers have not yet looked at CCN3’s activity in lactating women, but it is known that adding CCN3 to skeletal stem cells in a dish causes them to make something like cartilage and bone,” Ingraham says. “So we know that the human cellular target is responsive to this factor.” What’s still in question is whether lactating women have elevated CCN3 levels. Because the hormone works at very low levels, she adds, “the current reagents aren’t sensitive enough, so quite frankly we really need better technology” to detect it in blood. It’s also still unknown whether CCN3 gets into breastmilk to affect the bones of the infants consuming it, says Ingraham. “I think that’s a fascinating question.”

Ingraham is currently fielding calls from companies who are interested in harnessing CCN3 therapeutically. “They see the potential here for osteoporosis, fracture repair, dental implants and cartilage regeneration,” she says. “I think it would be wonderful if this could be a drug.” So far, the paper has been downloaded around 25,000 times, she says, “and I’m going to guess a fair fraction of that is women” concerned about bone loss. She adds: “We are living longer, and we understand that our bones and our skeleton are absolutely critical for healthy aging.”

References

1. Babey ME, Krause WC, Chen K, Herber CB, Torok Z, Nikkanen J, Rodriguez R, Zhang X, Castro-Navarro F, Wang Y, Wheeler EE, Villeda S, Leach JK, Lane NE, Scheller EL, Chan CKF, Ambrosi TH, Ingraham HA. A maternal brain hormone that builds bone. Nature. 2024;632(8024):357-365.
2. VanHouten JN, Wysolmerski JJ. Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice. Endocrinology. 2003;144(12):5521-9.
3. Lees CJ, Jerome CP. Effects of pregnancy and lactation on bone in cynomolgus macaques: histomorphometric analysis of iliac biopsies. Bone. 1998;22(5):545-9.
4. Augustine M, Boudreau R, Cauley JA, Majchel D, Nagaraj N, Roe LS, Sood P, Stewart AF, Horwitz MJ. Bone Mineral Density During and After Lactation: A Comparison of African American and Caucasian Women. Calcif Tissue Int. 2023;113(4):426-436.
5. Herber CB, Krause WC, Wang L, Bayrer JR, Li A, Schmitz M, Fields A, Ford B, Zhang Z, Reid MS, Nomura DK, Nissenson RA, Correa SM, Ingraham HA. Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones. Nat Commun. 2019;10(1):163.

They look like milk, act like milk, and are even called milk. But are plant-based milks nutritionally equal to cow’s milk or just healthy but unequal look-alikes? 

For consumers drinking an occasional glass of almond milk because they enjoy its nutty flavor, the nutritional differences between cow and plant-based milks may not seem terribly relevant. However, their growing popularity—recent surveys indicate between 40-60% of U.S. households purchase milks made from soybeans, nuts, grains, vegetables or fruits [1, 2]—suggests there could be valid public health reasons to be nutritionally nitpicky.

“Cow’s milk provides a lot of nutrients that are considered nutrients of public health concern,” explains Dr. Abigail J. Johnson, Assistant Professor and Associate Director of the University of Minnesota School of Public Health Nutrition Coordinating Center. Cow’s milk is a nutrient-dense food unique in its combination of nutrients, including calcium, phosphorus, zinc, potassium, riboflavin, magnesium, selenium, choline, vitamin B12, vitamin A, vitamin D (if fortified), and high-quality protein. 

 “We know plant-based milks can fit into a healthy dietary pattern,” says Johnson, “but if you are a consumer and are choosing to consume plant-based milk products [instead of cow’s milk], is your diet nutritionally adequate?” 

Johnson is the lead author of a new study [1] that addresses this question with one of the most comprehensive nutrient databases available, the University of Minnesota Nutrition Coordinating Center’s database of over 19,000 foods. The research team evaluated 219 plant-based milk alternatives (mostly soy-, almond-, or oat-based) representing 21 different brands currently available in the U.S. and compared the recommended daily values (DV) of their nutrients to those from low-fat (1%) cow’s milk [1].

This study went beyond comparisons of carton label nutrients and used an imputation approach that allowed the researchers to estimate nutrient content from the listed ingredients, including nutrients not required to be listed on nutrition labels [1]. “We have a team of data scientists that used sophisticated algorithms to take what we have on the label and then predict nutrients,” explains Johnson. “It is a bit like reverse engineering the ingredients to determine the [product’s] nutrients.” 

In total, they looked at values for 175 nutrients, nutrient ratios, and other food components and compared across all milks the daily values (DV) for nutrients that Americans might be at risk of under- or overconsuming (nutrients of public health concern). Nutrients that U.S. adults may not get enough of include vitamin D, calcium, potassium, and dietary fiber, iron for women of reproductive age, and protein and vitamin B12 for adults over 60, whereas those they may get too much of include saturated fats, sodium, and added sugars [1]. 

How did plant-milks measure up? The answer depends on which type and brand of plant milk and the nutrient of interest. 

“One of the things that resonated with me the most from this study was that plant-based milks aren’t monolithic,” Johnson shares. “There is massive variability across products and consumers need to be aware of that and make sure they are checking for particular nutrients.” 

The most variable nutrient was vitamin B12 [1]. One cup of low-fat cow milk provides roughly 50% of an adult’s DV for vitamin B12. Only 36% of plant-based milks evaluated provided at least 80% of the vitamin B12 provided by a serving of low-fat cow milk. And although 12% of plant-based milks in the database provided 100% DV of vitamin B12, more than half (52.5%) of the plant-based milks had no vitamin B12 at all [1]. These results corroborate previous studies that reported only half of commercially available plant-milks were fortified with some level of vitamin B12 [1]. 

Fortification with calcium and vitamin D also varied widely among plant-milk type and brand. Approximately 68% of the products in the database were fortified with both calcium and vitamin D, whereas 16% were not fortified with either nutrient [1]. Importantly for consumers, those that were fortified with calcium and vitamin D were done so to match levels of these nutrients in vitamin D fortified cow’s milk. 

When it came to naturally occurring (i.e., not fortified) nutrients, plant-based milks did offer some benefits cow milk could not. After all, plants are a source of many healthy nutrients that can get passed along during the milk-making process. For example, some plant-based milks had slightly more iron and dietary fiber than cow milk [1]. Whereas one cup of cow milk provides 0.4% DV of iron, the mean iron content for the plant-based milks included in this study was 4.6% DV [1]. Cow milk has no dietary fiber, but 11 (of the 221) products evaluated had more than 10% DV of dietary fiber [1]. And although most plant milks were lower in saturated fatty acids than 1% cow milk, saturated fats from dairy might not be as bad for your health as you’ve been led to believe. In fact, many studies suggest dairy fats could be beneficial in both child and adult diets.

In addition to comparing individual nutrients, the researchers also evaluated each plant-based milk’s overall similarity to cow milk’s nutritional profile. Of the 221 different plant-based milks, only three met the USDA’s nutrition standards for a fluid milk substitute, and these were all fortified soy milk [1]. The most recent edition of the Dietary Guidelines for Americans also acknowledged the nutritional similarities and recommended adults consume three servings of either dairy or fortified soy milk products to ensure meeting daily vitamin D and calcium requirements and a similar protein intake.

A note of caution about comparing nutrients between different foods—nutrients are not consumed individually but as part of whole foods. The label nutrients between soy and cow milk may match in quantity but can have different physiological consequences because of the food matrix in which they are delivered. As an example, one of the reasons soymilk products are recommended over other plant-based milk is because soy and cow milk both provide 8 grams of protein per serving. However, dairy is a source of high-quality protein that is difficult for soy protein to mimic entirely; milk proteins are highly digestible, provide all nine essential amino acids, and also increase the bioavailability of calcium and phosphorus delivered in milk. Moreover, cow milk provides many bioactive proteins that have demonstrated health benefits to adult consumers including glucose metabolism, controlling appetite, and building muscle. Johnson and colleagues have a similar note of caution about their findings [1]. They emphasized that their analytical approach did not allow them to evaluate protein quality or consider interactions within the food matrix that can influence bioavailability of minerals [1]. 

The results of this study are not presented with the intention to drive people away from plant-based milks, but rather to inform plant-based milk consumers exactly how their cow milk alternative may be leaving them short on essential nutrients. The high degree of variation within and between milk types (due to differences in fortification combined with nutritional differences in the starter beans, nuts, grains, fruits, or vegetables) means that consumers shouldn’t just passively select a carton. 

Johnson’s advice to consumers selecting plant-based milks over cow’s milk is simple: do your research. “Read the labels, figure out which nutrients you should focus on, and think about how you’ll get these nutrients in your diet.” 

Johnson and her research team also hope these results will help guide policy and future dietary guidelines. Survey data suggest most consumers of plant-based milks are selecting almond and oat milks rather than the recommended fortified soy milk [1]. Acknowledging these trends and educating consumers on the importance of reading labels and ingredient lists and including other dietary sources of calcium, vitamin D, vitamin B12, and even protein, if necessary, would be a helpful public health update for the next edition of the Dietary Guidelines for Americans.

References

1. Johnson AJ, Stevenson J, Pettit J, Jasthi B, Byhre T, Harnack L. Assessing the nutrient content of plant-based milk alternative products available in the US. Journal of the Academy of Nutrition and Dietetics. 2024 Jun 11.
2. https://www.strategicmarketresearch.com/market-report/plant-based-milk-market

Small, sugary molecules known as human milk oligosaccharides (HMOs) are the third most abundant component in a mother’s milk. They are critical players in the development of infant immune response and gut microbiome. HMOs are a diverse group of chemicals, and many factors determine the exact cocktail that a child consumes in milk. One key factor is a mother’s genetics. People with one form of the FUT2 gene produce an enzyme that adds a sugar named fucose to HMOs.  

Now, a new study suggests that the presence of these fucose-bearing HMOs can have a unique impact on an infant’s developing gut microbiome, and, as a result, affect their gut development and immune system [1]. 

People with the FUT2 allele are known as secretors, and those who do not are known as non-secretors. In previous studies, researchers have reported that mothers who are secretors and babies who consume their milk have higher levels of Bifidobacterium species in their gut microbiome, known to be a beneficial species [2]. Animal studies suggest that fucosylated HMOs can enhance immunity, reducing the incidence of necrotizing enterocolitis in mice and causing higher levels of antibodies against influenza [3]. “Thus far, no one had looked at whether a mother’s secretor status affected a baby’s gut microbes and thus, their immune system,” said the study’s senior author Laxmi Yeruva, a molecular microbiologist and immunologist at Microbiome and Metabolism Research Unit and Arkansas Children’s Nutrition Center in Little Rock, part of the United States Department of Agriculture-Agricultural Research Service (USDA-ARS). 

In the new study, Yeruva and her colleagues transplanted gut microbes from infants into germ-free mice. They used three groups of microbes: one from babies who were fed mother’s milk from secretor moms (SMM), another from babies of non-secretor moms (NSM), and a third from babies who were fed formula that was not fortified with HMOs (FM). 

Each group was then split into two, so one half of each was given supplemental HMOs in their diet. The experiments also included a germ-free control group of animals that did not receive supplements, and groups of mice were colonized with bacterial samples when they were 3 weeks old and again at 4 weeks of age. 

The researchers examined three factors: the bacterial populations in the animals’ gut microbiota, physical structure of the intestines, and immune differences amongst the various groups of mice.  

The team found that across all the groups, the gut microbiota in mice was most strongly correlated with the source of intestinal microbes. Supplementary HMOs in the diet had little impact on the gut microbial community. However, the gut microbiome had distinct features depending on whether infants were fed formula or mother’s milk from secretor mothers or non-secretor mothers. Mice with gut microbes from infants fed secretor mother’s milk had a higher proportion of Bacteroides and Bifidobacter species; NSM and NSM + HMOs groups had a higher abundance of Klebsiella, Enterocloster, and other species; FM and FM+ HMO groups had higher levels of Clostridium and Parabacteroides species. 

The researchers also observed differences in the intestines of each group, such as higher villi, fingerlike projections that help move nutrients into circulation, in the ileum of the NSM microbiome group, and longer cecal glands in the formula group. 

The group measured immune system differences in spleen samples, which help gauge systemic immunity, and in samples from the mesenteric lymph node, which reveal local immune response within the gut. They found that the SMM group had less inflammation when measured in the spleen. But mice with the HMO-supplemented, formula-based gut microbiota had stronger anti-inflammatory regulatory T-cell expression in the local lymph nodes. “It seems like maybe the response that’s generated in the gut in the formula fed group is not fully circulating in the system,” Yeruva said. 

Mice that had formula-raised gut microbes and HMO supplementation in their diets had the highest levels of circulatory immunoglobulin A compared to all the other groups. “I was very surprised with that,” Yeruva said. One possible explanation, she added, is that microbiomes from maternal milk-fed infants have already been exposed to HMOs, whereas HMOs are a new food for the formula group. “It’s brand new and they might be producing some specific set of metabolites in response so there is a better immunoglobulin A response.” 

Still, more work is needed to better understand how fucosylated molecules in human milk might shape the infant gut microbiome and immune system. Although the current study found few differences, Yeruva highlighted some possible explanations. The researchers did not study the secretor status of infants themselves, only the mothers. It’s possible that the transplanted microbiota could have already been influenced by fucosylated glycans produced in the infants’ intestines. Another source of variability is the mice themselves, since mouse intestines are also rich in fucosylated glycans. In ongoing and future studies, the researchers aim to home in on specific HMOs and elucidate the importance of specific molecules. 

References

1. Gurung M, Schlegel BT, Rajasundaram D, Fox R, Bode L, Yao T, Lindemann SR, LeRoith T, Read QD, Simecka C, Carroll L., Andres A., Yeruva, L. Microbiota from human infants consuming secretors or non-secretors mothers’ milk impacts the gut and immune system in mice. Msystems. 2024 Apr 16;9(4):e00294-24.
2. Wacklin P, Mäkivuokko H, Alakulppi N, Nikkilä J, Tenkanen H, Räbinä J, Partanen J, Aranko K, Mättö J. Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine. PLOS ONE. 2011 May 19;6(5):e20113.
3. Good M, Sodhi CP, Yamaguchi Y, Jia H, Lu P, Fulton WB, Martin LY, Prindle T, Nino DF, Zhou Q, Ma C. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine. British Journal of Nutrition. 2016 Oct;116(7):1175-87.