A new study by scientists at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University suggests that a micronutrient in human breast milk provides significant benefit to the developing brains of newborns, a finding that further illuminates the link between nutrition and brain health and could help improve infant formulas used in circumstances when breastfeeding isn't possible.
The study, published July 11 in the Proceedings of the National Academy of Sciences (PNAS), also paves the way to study what role this micronutrient might play in the brain as we age.
Researchers found that the micronutrient, a sugar molecule called myo-inositol, was most prominent in human breast milk during the first months of lactation, when neuronal connections termed synapses are forming rapidly in the infant brain. This was true regardless of the mother's ethnicity or background; the researchers profiled and compared human milk samples collected across sites in Mexico City, Shanghai, and Cincinnati by the Global Exploration of Human Milk study, which included healthy mothers of term singleton infants.
Further testing using rodent models as well as human neurons showed that myo-inositol increased both the size and number of synaptic connections between neurons in the developing brain, indicating stronger connectivity.
"Forming and refining brain connectivity from birth is guided by genetic and environmental forces as well as by human experiences," says Thomas Biederer, senior scientist on the Neuroscience and Aging Team at the HNRCA, senior author on the study, and faculty member at the Yale School of Medicine, where he leads a research group in the Department of Neurology.
Diet is one of the environmental forces that offers many opportunities for study. In early infancy, the brain may be particularly sensitive to dietary factors because the blood-brain barrier is more permeable, and small molecules taken in as food can more easily pass from the blood to the brain.
As a neuroscientist, it's intriguing to me how profound the effects of micronutrients are on the brain. It's also amazing how complex and rich human breast milk is, and I now think it is conceivable that its composition is dynamically changing to support different stages of infant brain development."
Thomas Biederer, senior scientist on the Neuroscience and Aging Team at the HNRCA, senior author on the study
Similar levels of myo-inositol across women in very different geographic locations point to its generally important role in human brain development, he observes.
Research by others has shown that brain inositol levels decline over time as infants develop. In adults, lower than normal brain inositol levels have been found in patients with major depressive disorders and bipolar disease. Genetic alterations in myo-inositol transporters have been linked to schizophrenia. In contrast, in people with Down's syndrome and patients with Alzheimer's disease and Down's syndrome, higher than normal accumulations of myo-inositol have been identified.
"The current research does indicate that for circumstances where breastfeeding is not possible, it may be beneficial to increase the levels of myo-inositol in infant formula," Biederer says.
However, Biederer says it is too soon to recommend that adults consume more myo-inositol, which can be found in significant quantities in certain grains, beans, bran, citrus fruits, and cantaloupe (but which is not present in great quantities in cow's milk). "We don't know why inositol levels are lower in adults with certain psychiatric conditions, or higher in those with certain other diseases," he says.
A host of research questions remain: Are lower inositol levels in people with depression or bipolar disease a cause of those diseases, or a side effect of drugs used to treat them? Do higher than normal levels in people with Down's syndrome and Alzheimer's disease suggest that too much myo-inositol is problematic? What is the "right" level of myo-inositol to have in one's brain for optimal brain health at various stages of life?
"My colleagues at the HNRCA and I are now pursuing research to test how micronutrients like myo-inositol may impact cells and connectivity in the aging brain," says Biederer. "We hope this work leads to a better understanding of how dietary factors interplay with age-related brain aberrations."
This work was supported by Reckitt Benckiser / Mead Johnson Nutrition and a gift from the Robert and Margaret Patricelli Family Foundation. Complete information on authors, funders, methodology, and conflicts of interest is available in the published paper.
Paquette, A. F., et al. (2023). The human milk component myo -inositol promotes neuronal connectivity. PNAS. doi.org/10.1073/pnas.2221413120.