Ultra-processed Foods (UPFs)

Ultra-processed foods (UPFs) have quietly taken over modern diets, making up nearly 60% of the average American's daily intake. Unlike whole or minimally processed foods, UPFs are industrial formulations packed with additives, artificial ingredients, and refined sugars and fats designed to enhance taste and shelf life—but at a significant cost to health. These foods don't just contribute to obesity and metabolic disorders; emerging research shows they actively rewire the brain, altering decision-making, impulse control, and reward processing in ways that drive overeating. Incredibly, studies reveal that even five days on a high-calorie UPF diet can impair white matter integrity in the brain, diminish reward sensitivity, and increase liver fat by 63%, all without noticeable weight gain.

The real danger of UPFs isn't just their calorie content but their ability to disrupt metabolic and neurological pathways before visible signs of disease appear. By altering insulin signaling in the brain and dampening satiety cues, these foods make overeating not just likely—but almost inevitable. While public policy changes could help curb their influence, individuals can take control by prioritizing whole, nutrient-dense foods that support brain and metabolic health. Understanding the science behind UPFs isn't just about avoiding weight gain—it's about protecting cognitive function, decision-making, and long-term well-being.

What are ultra-processed foods and why are they so harmful?

"In the United States, there are more than 10,000 ingredients allowed in food. Some of these—like microplastics and BPA—are added directly and some—including heavy metals—are indirectly added to the food during manufacturing."- Dr. Rhonda Patrick Click To Tweet

By definition, UPFs are "formulations of mostly cheap industrial sources of dietary energy (calories) and nutrients plus additives [created] using a series of processes and containing minimal whole foods." Most of them are less food, more lab experiment.

What makes UPFs so unique isn't just that they're high in sugar, fat, and calories, they also contain a multitude of harmful "ingredients" (chemicals) that could be detrimental to human health, including colorings, sweeteners, binders, preservatives, etc. In the United States, there are more than 10,000 ingredients allowed in food. Some of these—like microplastics and BPA—are added directly and some—including heavy metals—are indirectly added to the food during manufacturing. This includes:

• Nitrates/nitrites—preservatives in uncured meats that can form carcinogenic nitrosamines.
• Potassium bromate—added to package baked goods and linked to cancer.
• Butylated hydroxyanisol (BHA)—a preservative in cured meats linked to cancer.
• TBHQ—harms the immune system.
• Titanium dioxide—a color additive shown to cause DNA damage.
• Brominated vegetable oil—a stabilizer used in flavored drinks that can cause neurological harm.
• Per- and polyfluoroalkyl substances (PFAS or forever chemicals)—are used in food packaging like soups and are associated with cancer and reproductive system damage.
• Artificial colors (red 40, blue 1, etc.)—cause behavioral difficulties in children and exacerbate ADHD symptoms.
• Artificial sweeteners (e.g., aspartame)—linked to cancer.

They're also engineered to be extremely appetizing and less satiating—this causes people to eat more. A landmark study published in 2019 by obesity researcher Kevin Hall and colleagues found that consuming a diet high in ultra-processed foods caused participants to consume more than 500 calories per day more than when they ate a diet comprising unprocessed, whole foods. These calories came entirely from extra carbohydrate and fat intake, causing the participants to gain nearly 1 kilogram or 2 pounds in just 2 weeks.^[1]

Nutrient-matched meals produce different metabolic responses

The effects of UPFs may extend beyond how much people eat. In a 2026 randomized crossover study, 32 healthy-weight adults ate an ultra-processed meal and a non-UPF meal on separate days. Each provided approximately 300 calories, with closely matched carbohydrate, protein, fat, fiber, and estimated glycemic index. The non-UPF meal included egg, banana, dried cranberries, and cheese; the UPF meal combined foods such as deli-style turkey, instant mashed potatoes, a cookie, cereal, and veggie chips.^[2]

Over the following three hours, total glucose exposure did not differ significantly between meals, but the UPF meal produced a greater insulin response. Insulin concentrations were higher at 40, 60, 90, and 120 minutes, returning toward baseline by three hours; the insulin analysis included 31 participants. Similar glucose levels therefore concealed a difference in the body's handling of the meals. This acute response does not establish that the UPF meal caused chronic insulin resistance.

Fuel use also differed. After the non-UPF meal, participants shifted more strongly toward burning carbohydrates. The UPF meal blunted that shift toward carbohydrate oxidation, while fat oxidation remained relatively higher. Adjusting fuel use to nutrient availability is part of metabolic flexibility; greater fat oxidation in this setting is not evidence of greater body-fat loss.

On a separate day, participants viewed food pictures during functional MRI and indicated how much they would pay for each food. Among 29 people with both metabolic and imaging measurements, differences in carbohydrate oxidation were associated with differences in food-cue responses, including in the striatum, a region involved in learning and reward. Participants were not willing to pay more for UPFs overall. These associations do not show that one meal changed the brain or caused addiction.

The study tested one meal pair and did not isolate food structure, protein source, or additives as the cause. Participants had to finish the meals, so it did not test overeating. It nevertheless illustrates why calories, macronutrients, and glucose alone do not fully describe a food's physiological effects.^[2] Read the newsletter discussion.

UPFs cause metabolic and cognitive changes in less than a week

"...just 5 days of a high-calorie diet made the brains of these healthy, normal weight men structurally and functionally similar to people with obesity, and even after cutting the high-calorie foods out of their diet, these changes persisted for at least one week."- Dr. Rhonda Patrick Click To Tweet

The ways in which UPFs cause overeating aren't perfectly understood, but one study shed light on a potential mechanism that puts the brain—not the stomach—at the center of it all. The study included 29 men aged 19–27 who were assigned to one of two diets for 5 days: a high-calorie (ultra-processed) diet or a normal diet.^[3]

The high-calorie diet was, by design, higher in calories than the normal diet. Specifically, the participants consumed 1,500 calories more per day, provided in the form of highly processed, high-sugar, high-fat foods like candy bars, brownies, chips, and other snack foods.

The high-calorie diet didn't lead to weight gain or changes in body composition, reductions in insulin sensitivity, or even changes to inflammatory biomarkers like CRP and IL-6. However, over the course of just 5 days, liver fat increased by 63%.

Things really get interesting when we look at what happened to the participants' brains.

After 5 days of a high-calorie diet, brain insulin activity increased, specifically in the right insular cortex, left rolandic operculum, and right midbrain/pons. After high-calorie foods were removed and the participants resumed a normal diet for 7 days, insulin activity was lower, specifically the right hippocampus and bilateral fusiform gyrus.

The high-calorie diet didn't just alter brain insulin action—it profoundly rewired how the participants experienced reward. High-calorie eating reduced the participants' reward sensitivity and increased their punishment sensitivity, changes that persisted even after they resumed a normal diet. The high-calorie diet also impaired white matter integrity in brain regions responsible for reward and cognitive processing, which also outlasted the timeframe of the high-calorie diet.

Conclusions

These results are concerning for a few reasons, the first being that altered insulin signaling and activity of the brain's reward pathways happened quickly and in the absence of weight gain. This means they likely represent early "warning signs" that precede the development of obesity. It's very likely that UPFs change the way our brain works before they change the body—wiring us to overeat and experience food cravings differently.

In fact, insulin signaling in the brain might be a crucial pathway governing metabolic and behavioral changes resulting from UPF consumption even in the absence of changes in peripheral (think muscle or fat tissue) insulin sensitivity. The participants who had an exaggerated brain response to insulin had the greatest increases in liver fat and the greatest decreases in reward sensitivity.

It's shocking that just 5 days of a high-calorie diet made the brains of these healthy, normal weight men structurally and functionally similar to people with obesity, and even after cutting the high-calorie foods out of their diet, these changes persisted for at least one week. One can only imagine the massive rewiring that is going on with years and years of exposure to an ultra-processed diet that, unfortunately, has become the norm in the United States and elsewhere around the world.