Effect of Isocaloric Ultra Processed Versus Unprocessed Diets on Insulin Sensitivity

Nutrition science is beginning to place less emphasis on the nutrient composition of the diet
and more emphasis on its comprising foods. A particular public health concern involves the
consumption of foods that result from extensive industrial processing. Ultra-processed foods
have become increasingly common and now contribute the majority of calories consumed in
America. The rise in the prevalence of obesity, type 2 diabetes, and metabolic syndrome over
the past several decades is believed to have been caused, in part, by the parallel increase
in production, advertising, and consumption of ultra-processed foods. However, the metabolic
effects of industrial processing per se, independent of diet calories or macronutrient
composition, have not been carefully investigated in a controlled feeding study. Therefore,
we will conduct an inpatient controlled feeding study in 20 overweight and obese adult men to
investigate the changes in multi-organ insulin sensitivity and hepatic triglyceride content
resulting from consuming two test diets for a pair of 3 week periods. The test diets will be
implemented in a randomized, crossover design with each test diet following a 1 week run-in
period of inpatient controlled feeding of a standard metabolic diet. The test diets will be
matched for calories, macronutrient composition, sugar, fiber, and sodium, but one diet will
be composed of ultra-processed foods whereas the other diet will be unprocessed foods.
Multi-organ insulin sensitivity and hepatic triglyceride content will be measured at the end
of each 1 week run-in period as well as at the end of each 3 week test diet period.

- INCLUSION CRITERIA:

1. Adult men, age 18-50 years

2. Weight stable (< plus or minus 5 % over past 6 months)

3. Body mass index (BMI) greater than or equal to 25 kg/m^2

4. Plasma triglycerides > 150 mg/dl (Caucasian) or >140 mg/dl (African American)

5. Homeostatic model of insulin resistance (HOMA-IR) > 2

6. Able to complete daily bouts of stationary cycling at a moderate rate and
intensity with a HR equal to or greater than 0.3x(220-age-HRrest)+HRrest but not
exceeding 0.6x(220-age- HRrest)+HRrest and no signs of arrhythmia

7. Written informed consent

8. Willing to eat all the food provided in the study

9. Willing to cease their habitual caffeine intake during the study, beginning one
week prior to each inpatient admission

EXCLUSION CRITERIA:

1. Evidence of metabolic or cardiovascular disease, or disease that may influence
metabolism (e.g. cancer, diabetes, thyroid disease)

2. Body weight >400 lbs. (weight limit of magnetic resonance spectroscopy gantry)

3. Taking any prescription medication or other drug that may influence metabolism (e.g.
diet/weight-loss medication, asthma medication, blood pressure medication, psychiatric
medications, corticosteroids, or other medications at the discretion of the PI and/or
study team)

4. Hematocrit < 40%

5. Participating in a regular exercise program (> 2h/week of vigorous activity)

6. Caffeine consumption > 300 mg/day

7. Regular use of alcohol (> 2 drinks per day), tobacco (smoking or chewing)
amphetamines, cocaine, heroin, or marijuana over past 6 months

8. Past or present history of eating disorder (including binge eating) or psychiatric
disease, including claustrophobia since part of the protocol will involve being
confined to a small room for whole-body indirect calorimetry and being in an MRI
scanner for liver fat measures

9. Implants, devices, or foreign objects implanted in the body that interfere with the
Magnetic Resonance procedures.

10. Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food
allergies)

11. Volunteers unwilling or unable to give informed consent

12. Non-English speakers due to unavailability of required questionnaires in other
languages.