July 2, 2019

Ultra-processed Food Consumption, Appetite, and Weight Gain

Are all calories equal?
Sophisticated inpatient trial and several other new studies confirm the harm of ultra-processed foods.


Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metabolism. 2019;30:1-11.


Randomized controlled trial


To determine the impact of an ultra-processed diet compared to an unprocessed diet on appetite and weight gain


The study included 20 adult inpatients (mean age 31.2) at the National Institutes of Health (NIH) Clinical Center; participants had a stable weight and an average BMI of 27.


Participants accessed either a highly processed food selection or an unprocessed food selection and were instructed to eat freely (ad libitum) for 2 weeks. Meals were matched for available calories, energy density, sugar, fiber, sodium, and macronutrients. Each cohort crossed over to the other arm after 2 weeks. There was no washout period.

Outcome Measures

Calorie consumption and change in weight were the primary outcome measures. Nutrient intake, appetite, energy expenditure, physical activity, and energy balance were also tracked.

Key Findings

During the 2 weeks with the ultra-processed food diet, caloric intake increased by approximately 500 calories per day (508 ± 106 kcal/day; P=0.0001). There was also increased intake of carbohydrate (280 ± 54 kcal/day; P<0.0001) and fat (230 ± 53 kcal/day; P=0.0004); no significant changes were observed in protein intake (−2 ± 12 kcal/day; P=0.85).

Not surprisingly, weight changes correlated closely with caloric intake. The participants gained weight (0.9 ± 0.3 kg; P=0.009) on the ultra-processed food diet, and they lost weight (0.9 ± 0.3 kg; P=0.007) on the unprocessed food diet. Again, these changes happened in 2 weeks on each diet.

Practice Implications

We almost didn’t want to cover this study because our initial response was ”of course processed food consumption led to weight gain!” This is likely the response of integrative practitioners worldwide who question the safety of ultra-processed foods. And yet it’s hard to believe that this is really the first randomized controlled trial to demonstrate that a highly processed diet is associated with weight gain.

Past publications have hinted at the connection. A 2017 review by Poti et al stated that “evidence suggests” a harmful connection between ultra-processed food consumption and obesity.1 Those researchers also identified an association between ultra-processed food and increased risk of metabolic syndrome, increased total and low-density lipoprotein (LDL)-cholesterol, and risk of hypertension.

This new randomized inpatient trial corroborates our existing understanding and long-held belief about a highly processed diet—that it could be a key factor in the increasing obesity epidemic. Furthermore, once you really dig into the details of the study and the sophisticated nature in which it was carried out, there is so much to appreciate about this trial.

Similar to the commentary we did in the June issue of the Natural Medicine Journal regarding low-carb eating,2 this study demonstrates that the old adage “a calorie is a calorie” is an oversimplification.

A key aspect of this study was the researchers’ ability to control food intake in both cohorts. The 2 diets contained roughly the same availability of carbohydrates, fats, and protein. In addition, the study mimicked real world choices, with the ultra-processed choices featuring foods that ordinary, moderately health-conscious Americans might eat every day.

For example, breakfast for the processed food group could include a bagel with cream cheese and turkey sausage, whereas the unprocessed diet would be oatmeal with raw almonds, blueberries, and 2% milk.

A processed lunch example is a lunch meat and cheese sandwich on white bread with diet lemonade and low-fat chips, while the unprocessed lunch would be salmon, sweet potato, and plain yogurt with strawberries.

So it’s not as if the processed diet featured a daily dose of pepperoni pizzas, sugary sodas, fries, and doughnuts. The big difference in the processed menu was the ubiquity of what are termed ultra-processed foods: breakfast cereals, muffins, chips, white bread, (seemingly virtuous) sugary flavored yogurts, low-fat potato chips, fruit juices, and diet drinks. That adds up to an abundance of artificial sweeteners, preservatives, emulsifiers, added sugars, flavor enhancers, sodium, and unnatural oils.

This new randomized inpatient trial corroborates our existing understanding and long-held belief about a highly processed diet—that it could be a key factor in the increasing obesity epidemic.

Another interesting outcome of this study is the effect of ultra-processed foods on appetite. This study confirms that a highly processed diet increases appetite. This is likely through stoking the hunger hormone ghrelin, whereas the unprocessed diet likely curbed ghrelin and amped up the satiety hormone peptide tyrosine tyrosine (PYY).3,4 Future studies of similar design could use such labs to further delineate the mechanism of the increased caloric consumption with processed food.

While this study is unique in many ways and speaks specifically to weight gain, there have been other studies demonstrating additional health effects of a highly processed diet. A 2018 prospective cohort by Filot et al demonstrated an association between ultra-processed food intake and breast cancer, as well as other cancers.5 The researchers found that for every 10% increase in ultra-processed foods in the diet, there was a corresponding 12% increase in overall cancer risk and an 11% increased risk of breast cancer.

In their recent 2019 observational prospective cohort study featuring nearly 45,000 participants, Schnabel et al demonstrated that an increase in the consumption of ultra-processed food was associated with overall higher risk of all-cause mortality.6

In addition, 2 large studies published just last month in BMJ found a positive association between the consumption of ultra-processed foods and the risk of cardiovascular disease and death. In the first study by Srour et al, more than 105,000 French adults were asked to complete a questionnaire that identified 3,300 different food items that were grouped according to the level of processing. Similar to the breast cancer study, these researchers found that a 10% proportional increase in ultra-processed foods led to a 12% increase in overall cardiovascular disease, a 13% increase in heart disease, and an 11% increase in cerebrovascular disease.7

In the second study, Spanish university graduates with an average age of 38 were also given a dietary questionnaire.8 In that study, more than 4 servings a day of ultra-processed foods was associated with a whopping 62% increased risk of all-cause mortality compared to less than 2 servings per day. They also found that for every added daily serving (above 4) of ultra-processed food, mortality risk was increased by 18%. In both of these studies, the researchers concluded that policies are urgently needed to limit the consumption of ultra-processed foods. We couldn’t agree more.

Evidence is mounting and the case to limit or avoid ultra-processed foods is stronger than ever before. In addition to contributing to our present obesity epidemic, evidence suggests that ultra-processed foods are likely key contributors to a wide range of chronic and deadly conditions such as cancer and heart disease.

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  1. Poti JM, Braga B, Qin B. Ultra-processed food intake and obesity: what really matters for health—processing or nutrient content? Curr Obes Rep. 2017;6(4):420-431.
  2. Hoffman R, Gazella KA. Is low-carb the key to lasting weight loss? Natural Medicine Journal. 2019;11(6).
  3. Lv Y, Liang T, Wang G, Li Z. Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism. Biosci Rep. 2018;38(5). pii: BSR20181061.
  4. Pulkkinen L, Ukkola O, Kolehmainen M, Uusitupa M. Ghrelin in diabetes and metabolic syndrome. Int J Pept. 2010;2010:248948.
  5. Fiolet T, Srour B, Sellem L, et al. Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort. BMJ. 2018;360:k322.
  6. Schnabel L, Kesse-Guyot E, Alles B, et al. Association between ultraprocessed food consumption and risk of mortality among middle-aged adults in France. JAMA Intern Med. 2019;179(4):490-498.
  7. Srour B, Fezeu LK, Kesse-Guyot E, et al. Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Sante). BMJ. 2019;365:1451.
  8. Rico-Campa A, Martinez-Gonzalez MA, Alvarez-Alvarez I, et al. Association between consumption of ultra-processed foods and all cause mortality: SUN prospective cohort study. BMJ. 2019;365:1949.