Maryanne Perrin, MBA, and ILCA volunteer
Research over the last several decades has highlighted WHAT makes human milk so amazing — it’s associated with reduced risk of infections, asthma, obesity, diabetes, leukemia, and necrotizing enterocolitis (NEC), just to name a few. Determining HOW human milk delivers these benefits (referred to as “the mechanisms”) is less fully understood, though researchers around the world are working on these questions. A study published last month in the journal Pediatric Research gave some interesting insights on a potential human milk mechanism that is involved in protecting against NEC.
Photo by derPlau via Flickr Creative Commons
First, a little background information: Most of the fat in our diet is found in the form of triglycerides, a “suitcase” that carries three (thus the “tri”) fatty acids bound to a glycerol backbone. To absorb these fats, our bodies first break off the fatty acids, producing free fatty acids (FFAs), which are packaged into micelles and absorbed via the intestinal epithelial cells, and then repackaged into triglycerides for transport to other tissues.
Researchers at the University of California, San Diego wondered whether there was a difference in the toxicity of digested human milk (HM) compared to infant formula (IF), so they used an in-vitro model to study what happened to various cells when exposed to digested HM and IF. This involved mixing HM and IF in test tubes with various enzymes to simulate the digestive process, and then exposing three different cell types to the digested content: human neutrophil cells (a white blood cell that is involved in the early response to infections); cow heart endothelial cells, and rat intestinal epithelial cells.
What did they find?
Digested infant formula had significantly higher levels of FFAs than digested human milk (more triglycerides were cleaved) and it also had significantly higher death rates of neutrophils during a two hour exposure (ranging from 47 – 99% depending on the formula brand compared to a 6% death rate during exposure to digested human milk). Results were similar for the death of cow heart cells and rat intestinal cells. The likely mechanism for the cell death is the elevated level of FFAs which act as detergents and rupture cell membranes. When FFA levels were reduced by inhibiting the enzyme that cleaves triglycerides, cell death was also reduced.
Infant formula is designed to have a similar fat content to human milk, so what could cause the elevated FFAs levels that contribute to necrosis? The authors speculated on several things including the way triglycerides are delivered in human milk (they are in larger globules than in infant formula, potentially making them less digestible by lipase enzymes), the possibility that human milk deactivates enzymes that digest fat (or infant formula activates them), and the different structure of the triglycerides (human milk puts the long chain fatty acids in the #2 position on a triglyceride, making them less digestible, while in infant formula, the long chain fatty acids are primarily located at position #1 or #3 on the glycerol backbone, which is preferentially cleaved by digestion enzymes).
The mechanism described in this study is not pathogen driven, but instead driven by a cytotoxic environment that leads to premature cell death. Other potential NEC mechanisms were reported in the last year that involved bacteria; one study done in a rat model showed that the oligosaccharides in human milk bind pathogens that cause NEC, while another study showed that bacteria that grew on human milk formed a potentially protective biofilm. All of these studies were done in a test tube or in animal models, which means more research is needed to determine whether these mechanisms also operate in humans.
Collectively these studies suggest that human milk potentially has a variety of “tools in its toolbox” for protecting the immature and developing infant. Does this surprise you?!
Maryanne Perrin loves all things related to food: growing it, cooking it, eating it, and now studying about it at the molecular and cellular level. She has a BS in Industrial Engineering from Purdue University and an MBA from the University of North Carolina, Chapel Hill, and enjoyed a variety of career paths (information technology, management consulting, stay-at-home-mom, entrepreneur) before returning to school to obtain a PhD in Nutrition Science. She was quickly captivated by the amazing story of human milk and is focusing her research on understanding the nutritive and immunoprotective value of donor milk beyond one year postpartum. When she’s not studying or helping ILCA with social media, she likes playing in the woods with her husband, three kids, and the family dog.
