Notes on Engineering Health, January 2022

On Human Breastmilk & Personalized Nutrition

Human breastmilk is a living, dynamic fluid that supports the optimal nutrition of infants. It has an incredibly wide range of nutrients, immune factors, hormones, and metabolites. While many of these components are stable during lactation, some vary significantly in response to maternal diet, infant health, time of day, or whether the meal is starting or ending. In many ways, human milk is the ultimate personalized nutrition.

But, in nutrition, knowing what will actually make a difference in health outcomes is not easy, and the data needed to establish baseline knowledge is hard to collect. For instance, many claims have been made about the benefits of breastmilk over formula — better mother-infant bonding, lower infant mortality, fewer infections in infancy, higher IQ, higher wages in adulthood, less cancer, to name a few — but the analyses that led to these conclusions seldom hold up under rigorous scrutiny.

In this note, we have focused on the composition of human breastmilk and tried to draw some lessons from how it changes to adapt to the needs of the infant in orienting our thoughts toward developing better diets later in life.

Most human breastmilk components are synthesized by the mammary gland, while others originate from maternal blood, adipose tissue, or the maternal diet. The composition of human milk changes markedly from colostrum (produced immediately following birth and for a few days thereafter) which is low in lactose and rich in proteins, especially antibodies and growth factors, to mature milk that is relatively stable in composition from two weeks post-partum until weaning.

The composition of human breastmilk breakdowns as follows:

Carbohydrates: The predominant carbohydrate is lactose which contributes 40% of energy content, much higher than is found in milk from other mammals, and is ideally suited to the energy needs of the infant’s rapidly growing brain. On top of the most common lactose and fructose, more than 100 other human milk oligosaccharides (HMOs) have been identified, with a huge diversity across women, varying according to maternal genetic factors. HMOs have limited nutritional value as only about 1% of them are absorbed from the GI tract. However, they have important roles to play as prebiotics in shaping the gut microbiome, providing antimicrobial and antiviral protection, and in mucosal barrier maturation. They may also play an important role in cognitive development and some interesting evidence is emerging about the role of 2-FL in this regard.

Fats: Human breastmilk fat supplies about 50% of the energy in milk and supports the development of the Central Nervous System, immune function, and inflammatory responses. The fat fraction comprises 98% triglycerides with saturated, mono-unsaturated, and polyunsaturated fatty acids. The polar lipids that comprise 2% of the milk fat are situated within the milk fat globule membrane and include complex phospholipids, gangliosides, sphingomyelin, and cholesterol. Though a tiny fraction of the fat portion of milk, these components have a vital role to play in brain development.

Proteins: The protein in human milk is highly bioavailable and its concentration diminishes rapidly as the infant grows. The proteins are predominantly caseins and whey proteins, but there are also enzymes, endogenous peptides, and mucins. Some estimates put the number of proteins above 1,500 with an ever-changing composition as lactation proceeds. Human milk also contains many cell-signaling proteins or adipokines, some of which come from maternal adipose tissue, and some of which are synthesized by the mammary epithelial cells. The function of many of these factors is still being determined, but they are thought to play a role in regulating infant appetite among other things.

Micronutrients: Human breastmilk also contains a diverse range of micronutrients all necessary for processes related to growth and development. Of particular importance are zinc, copper, iron, and Vitamin D.

Two striking examples illustrate how changes in milk composition provide the growing child exactly what is needed to meet her nutritional needs at each stage of development:

1) In colostrum, we find alpha-lactalbumin, lactoferrin, and secretory IgA but these components are present in much-reduced amounts in mature milk.

2) Breast milk contains three times more cortisol in the morning than in the evening and the concentration increases overall from two weeks to 12 weeks. Cortisol is a hormone responsible for some circadian patterns and is thought to promote alertness and the longer-term programming of infant metabolism. The link between cortisol levels and infant health outcomes still needs research but such a finely regulated system hints at its importance in healthy development.

Can we use this model of tuned nutrition to arrive at improved nutritional products for people at other stages of life well beyond infancy? To some extent, nootropics are being shaped to meet the needs of unique subgroups. Originally designed to meet the needs of gamers (mostly the need to sustain sitting for long periods of time while staying mentally sharp enough to complete their gaming task, often killing monsters), we now see products for the unique nutritional needs of people engaged in, for example, extreme sports. This approach also embraces the field of medical nutrition, a specialized regulatory category where foods are formulated for the changed metabolic needs of individuals with an underlying disease condition. Medical foods are designed to be used under the guidance of a physician and combined with other drugs can be a powerful tool in combating cancer. This level of personalization might actually be required when designing diets as shown by a recent Science publication. When looking at caloric restriction diets, they observed that the effects of the diet on life span are highly dependent on genotype and, in some cases, cause reduced survival. The studies necessary to be able to properly prescribe precision diets are hard to conduct, but thoroughly needed. While we are just at the beginning of the arduous route towards N of 1 diet recommendation, there is no doubt it is a worthy endeavor.

One aspect that is left out of this note is that food is more than mere sustenance and humans eat not only to nourish their bodies but also their social lives, their memories, and their souls. Searching for better scientifically-driven diets is necessary, but let’s not forget to draw pleasure from it too. With these thoughts, everyone at Digitalis wishes you a happy New Year!

Steve Allen, Jonathan Friedlander, PhD & Geoffrey W. Smith

First Five

First Five is our list of essential media for the month which spans a range of content including scientific papers, books, podcasts, and videos. For our full list of interesting media in health, science, and technology, updated regularly, follow us on Twitter or Instagram.

This month’s section is dedicated to exercise (#NewYearsResolutions):

1/ Exercise in the morning, exercise in the evening
Exercise causes the body to release hundreds of different signals that improve our health in many different ways. Now scientists have mapped these intrinsic signals and how they are released by different organs in mice following exercise at different times of the day. Their ‘Atlas of Exercise Metabolism’ is a major step toward developing more effective exercise routines that are timed to the body clock.

2/ Exercise to be more creative
On ne peut penser et écrire qu’assis (G. Flaubert). Here I have got you, you nihilist! A sedentary life is the real sin against the Holy Spirit. Only those thoughts that come by walking have any value.
— Friedrich Nietzsche, The Twilight Of The Idols, Maxim 34.

The debate between Flaubert and Nitzsche has not been settled, but some recent evidence adds to the feud by showing that restrictions of movement impaired divergent thinking. Indeed, even small movements while sitting seem to improve creativity.

3/ Exercise to stay youthful
When 2-year old mice were studied after two months of progressive weighted wheel running, despite having no prior training, it was determined that they were the epigenetic age of mice eight weeks younger than sedentary mice of the same age.

4/ Exercise to stay sharp
The benefits of exercise on cognitive aging and neurodegeneration have been known for some time. A new study pinpoints the role of a protein, clusterin, in boosting memories and reducing neuroinflammation. The researchers did so by showing that blood from marathoner mice could boost brain function in their couch-potato counterparts. This is in no way an invitation to bleed your gym-going friends but rather for all of us to be less sedentary!

5/ Exercise to prevent death (?)
A recent study in JAMA Internal Medicine based on accelerometer measurements examining the association of physical activity and mortality shows that adding 10 minutes per day of moderate-to-vigorous physical activity was associated with the prevention of 8.0% of total deaths per year among men, 5.9% among women or a total of about 110,000 deaths per year in the US alone. Some of these trends could be linked to the fact that excise seems to reduce the risk of developing Type 2 diabetes among other diseases.

Digitalis Ventures


Participated in Series Seed funding co-led by Khosla Ventures and Future Ventures with addition participation from S2G Ventures, KdT Ventures, Agfunder, Cantos and Unshackled.
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Digitalis Commons

Public-Interest Technologies for Better Health

Digitalis Commons is a non-profit that partners with groups and individuals striving to address complex health problems by building public-interest technology solutions that are frontier-advancing, open-access, and scalable.

The Arc Institute has launched recently with an immediate goal of freeing Arc researchers to focus on their most important ideas in the study of complex human diseases. In their words:

Arc Institute faculty will have unprecedented ability to pursue curiosity-driven science, since Arc will fully fund salary, staff, and projects for renewable eight-year terms. The funding for these labs, which we envision will grow to 10–20 people each, is completely flexible because we are betting on people rather than specific project ideas. By “pre-funding” our scientists, we hope to avoid the Gordian knot of incentives that currently entangles grant funding success, single-author credit, and high-impact publications. We hope to incentivize high-risk, high-reward research, long-term problem solving, and cross-specialty collaboration.

Digitalis Commons applauds the commitment of Arc’s founders and funders to seek out new ways to finance the search for great new ideas in the pursuit of improving human health.



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