EPG, high-protein snacks, GLP-1 drugs, and the part of weight loss nobody puts on the nutrition label
When I taught anatomy and physiology, I always looked forward to the weeks when we reached the digestive system.
There was something wonderfully strange about teaching it.
The digestive tract is an open tube. Food enters at one end, travels through a remarkably complicated system of organs, and eventually leaves at the other. In a sense, everything inside that tube is still technically outside the body until it crosses the intestinal wall and becomes part of us.
That idea always fascinated me.
It also made for some of my favorite lectures.
I had a lecture on gas that could reliably get an entire classroom laughing. Farts are funny. They were when I was teaching, and I suspect they always will be. Underneath the laughter was a serious physiological lesson. What happens in the digestive system depends on what we eat, what gets digested, what gets absorbed, what the microbes encounter, and what eventually has to leave.
Years later, that is the part of digestion I find myself thinking about again.
We spend an enormous amount of time talking about what goes into our bodies.
Calories. Protein. Fat. Fiber. Medication.
We talk much less about what doesn't get absorbed.
That seems particularly interesting right now because we are entering a new era of weight loss. We have drugs that change appetite and gastrointestinal physiology. We have foods engineered to deliver more protein with fewer calories. And we have fat replacers designed to provide the taste and texture of fat while allowing much of the material to pass through the digestive system without being absorbed.
We have become remarkably good at engineering what enters the body.
But the digestive system still has to deal with everything that comes out the other end.
And that brings me back to something we learned the first time we tried to make fat disappear.
Olestra.
We Have Been Here Before
In the 1990s, there was another revolutionary idea.
Olestra was a fat substitute designed to provide the taste and texture of fat without being absorbed like ordinary dietary fat. The idea was compelling: eat the foods you enjoy, but absorb fewer calories.
The problem was what happened afterward.
Olestra could cause gastrointestinal symptoms, particularly when consumed in larger amounts. Diarrhea, urgency, gas with discharge, oily spotting, and oily stools became associated with the product. The phrase "anal leakage" became so closely connected with Olestra that it eventually became part of the cultural memory of the product.
The science was more complicated than the headlines suggested. Controlled studies did not find that everyone consuming Olestra developed severe gastrointestinal problems, and some large studies found relatively modest differences in symptoms.
Olestra demonstrated an important principle.
When you design a substance to resist digestion and absorption, you haven't eliminated it. You have changed where it goes.
Olestra also interfered with the absorption of some fat-soluble vitamins, leading to fortification requirements. The ingredient solved one nutritional problem while creating new considerations elsewhere in the digestive system.
That history is important because we are now seeing a newer generation of ingredients designed around a similar basic concept.
Studies Control the Dose. The Consumer Controls the Snack.
EPG, or esterified propoxylated glycerol, is a newer fat replacer designed to provide the functional properties of fat while contributing substantially fewer calories because much of it is not absorbed. FDA has issued "no questions" responses to multiple GRAS notices covering specified uses of EPG in foods.
The distinction from Olestra, especially for marketing teams, is important. EPG was developed with different chemical properties and formulations intended to reduce some of the problems associated with earlier fat substitutes.
Studies have found EPG generally well tolerated at lower consumption levels, and human studies have examined exposures of 10, 25, and 40 grams per day.
The interesting question is what happens when a technology that looks well controlled in a study encounters actual consumer behavior.
A study can give participants a defined amount of a product every day.
The consumer sees a snack.
People don't necessarily eat according to the dose used in a study. They eat when they're hungry. They eat when nervous or stressed. They eat while watching television. They eat because the product tastes good. They eat another serving because the package says the food has fewer calories.
Olestra consumption data illustrate why this matters. Average chronic exposure was relatively low, but estimated acute consumption on individual snack occasions could be substantially higher.
So, the question for EPG isn't only whether a particular amount is tolerated.
It is also whether real-world consumption can push exposure substantially beyond the amounts used in controlled studies.
The laboratory controls the dose.
The consumer controls the snack.
We Are Changing Much More Than Fat
EPG is entering a food environment very different from the one in which Olestra was introduced.
Protein has become a major selling point. The shelves are filling with protein bars, protein chips, protein cookies, protein drinks, and other products designed to deliver more protein with fewer calories.
Many of these foods contain ingredients that can affect the gastrointestinal system. Sugar alcohols, added fibers, gums, lactose, and certain sweeteners can contribute to bloating, gas, or changes in bowel habits in some people.
Then, there are GLP-1 drugs.
These medications have changed the weight-loss landscape by altering appetite, satiety, and gastrointestinal physiology. They also commonly produce gastrointestinal side effects. Nausea, diarrhea, constipation, vomiting, and changes in gastric emptying are well documented.
People increasingly combine these strategies.
Someone taking a GLP-1 medication may eat smaller meals while also choosing high-protein foods and lower-calorie products containing fat replacers.
Someone else may be eating substantially more fiber than they did before.
Another person may be using several of these strategies at once.
The modern weight-loss consumer isn't following a single intervention in isolation.
The intestine sees the total exposure.
We Still Need Fat
There is an uncomfortable truth in any discussion about replacing dietary fat:
We need fat.
Fat is not simply a delivery system for calories. Lipids are fundamental components of cell membranes and involved in signaling, energy storage, and countless processes that keep cells functioning.
The nervous system depends on lipids. Myelin, the insulating material that surrounds many neurons, is extraordinarily rich in lipids.
The body also needs certain fatty acids from the diet because it cannot make them itself. Different dietary fats provide different combinations of fatty acids, and those molecules become part of the biology of the cells that use them.
EPG cannot replace those biological functions. It replaces some of the calories normally delivered by fat while allowing much of the EPG to pass through the digestive system without being absorbed.
That may be an entirely reasonable energy-reduction strategy.
It also raises a different question: what happens to the material that remains in the digestive tract?
What Happens at the Other End?
This may be the least glamorous question in nutrition science.
It may also be one of the most revealing.
If a material is deliberately designed to resist digestion and absorption, the material must exit the body.
EPG has been studied for gastrointestinal effects, and the results are worth examining carefully.
At lower exposure, the effects appear relatively limited. In one eight-week study, oily spotting was the only predefined gastrointestinal event significantly more frequent than control at 10 grams per day. At 25 and 40 grams per day, several gastrointestinal events occurred more frequently, including gas with discharge, diarrhea, oily spotting, oily evacuation, oily stool, liquid stool, and soft stool.
That does not mean everyone consuming EPG will experience these effects. It shows that exposure can change the gastrointestinal experience.
The physical form matters as well.
Earlier development work found that liquid forms could produce passive oil leakage at lower concentrations. That was one reason development focused on semisolid and solid formulations with melting characteristics intended to reduce the possibility of oily leakage.
That is an important formulation lesson.
A calorie calculation can tell you how much energy a food delivers.
It doesn't necessarily tell you how the food will behave inside the digestive tract.
For the person eating it, however, that distinction can become very real.
Oily material in the stool can affect wiping, residue, urgency, and everyday comfort.
Those details belong in the conversation about how a food actually performs.
The Consumer Is Not a Single-Ingredient Experiment
EPG was evaluated as an ingredient in specified food uses.
The consumer is not a single-ingredient experiment.
Real-world exposure is a stack.
A fat replacer.
A high protein load.
Poorly absorbed carbohydrates.
Added fiber or sugar alcohols.
A medication that changes appetite, gastric emptying, intestinal motility, or meal size.
The biology receives all of them.
Clinical trials are generally designed to answer specific questions about specific interventions. A food study may carefully control the amount of an ingredient participants consume. A drug trial may carefully control medication exposure.
Real life is messier.
People change their diets when they start losing weight. They add protein. They reduce calories. They try new products. They change meal sizes. They take medications. They stop taking medications. They respond differently to all of it.
We have excellent tools for studying individual pieces of this system.
We have a much less developed framework for studying the stack.
We need one.
That framework would have to look beyond whether each individual intervention works on its own. It would need to examine how combinations change gastrointestinal symptoms, nutrient absorption, stool characteristics, microbiome activity, medication tolerance, and long-term adherence.
That is a much more interesting research problem than simply asking whether a single ingredient is safe at a particular dose.
The Question We Should Be Asking
For decades, nutrition has given us a remarkably simple vocabulary for describing food.
Calories consumed.
Protein consumed.
Fat consumed.
Fiber consumed.
But consumption is only the beginning.
What gets absorbed?
What gets metabolized?
What reaches the colon?
What gets transformed by the microbiome?
What allows the microbiome to flourish?
What eventually goes to the toilet?
Those questions become increasingly relevant as we engineer foods and medications to change the normal relationship between eating and energy absorption.
A food that helps someone consume fewer calories while preserving the pleasure of eating can be valuable. A medication that reduces appetite and helps someone lose substantial weight can be transformative. A protein snack with fewer carbohydrates can make it easier to meet dietary goals.
Each intervention changes the physiological environment in which the others operate.
The human body is not simply a calorie calculator. It is part of the product.
Before trying any combination of these weight loss products, get a stool base panel to pair with symptom tracking, medication timing, and food logs. This creates a strong individual downstream profile. If new complications arise, a treatment plan can be created.
And perhaps there is another way we can examine this biology.
And Then There Is the Sewer
This is where I want to make a deliberately massive leap.
Or maybe it isn't as massive as it sounds.
We already use wastewater to monitor biological and chemical signals moving through populations. Researchers can detect traces of viruses, pharmaceuticals, drugs, hormones, metabolites, and other compounds in wastewater.
The sewer is, in a very strange way, a record of what a population has consumed, processed, and eliminated.
So what happens if we start thinking about it as a nutritional laboratory?
A population-level nutritional laboratory without sending it over the internet.
Imagine combining wastewater measurements with prescription data, food consumption trends, pharmaceutical sales, clinical outcomes, and population health data.
As analytical technologies become more sensitive, wastewater could potentially provide another way to observe changes occurring across a population as large numbers of people adopt the same medications or dietary strategies.
Weight-loss drugs are an obvious example.
If a medication or its metabolites are present in measurable forms in wastewater, population-level patterns of use or exposure could potentially be studied alongside prescription and health data.
The same concept could eventually be applied to other measurable metabolites associated with diet, medication, or gastrointestinal physiology.
A wastewater sample would provide a population-level biological signal that could be compared with information collected by public health agencies, healthcare systems, and other sources.
Clinical trials would still provide the controlled evidence. Wastewater could provide something different: a view of what is happening across an entire population.
And there is another interesting possibility.
Wastewater could eventually become a way to study the downstream consequences of changing what people eat.
If dietary patterns change dramatically across a population, the chemical and biological composition of wastewater changes too.
That gives researchers another window into the collective result.
The laboratory controls the dose.
The consumer controls the snack.
The sewer sees the population.
The Open Tube
When I taught anatomy and physiology, I used to tell my students that the digestive system was an open tube.
At the time, it was mostly a useful way to explain anatomy.
Years later, I think there is more to that simple description. Everything that enters the tube has a destination. Some things are broken down. Some are absorbed. Some are transformed by the microbes living there. And some continue all the way through.
We have become remarkably sophisticated at engineering what enters that tube.
We can change appetite with drugs.
We can increase protein.
We can reduce calories.
We can make fat-like foods that contain substantially less absorbable energy.
Those are extraordinary advances.
The next step may be paying closer attention to what happens downstream. Every intervention changes the biology somewhere. Every material that resists absorption has to go. Every new food changes the mixture moving through the digestive tract and the microbes involved. Every medication leaves some measurable trace of its journey.
The biology doesn't end when the nutrition label does.
Maybe the next frontier of weight-loss science isn't the bathroom scale.
Maybe it's the tube that leads to the sewer.
