Impacts of minimally-processed omnivorous vs lacto-ovo-vegetarian diets on insulin sensitivity, lipid profile, and adiposity in older adults: Secondary findings from a randomized crossover feeding trial

BACKGROUND AND AIMS: The aging population in the U.S. faces increased cardiometabolic risk, reducing healthspan and increasing public health burden. These vulnerabilities may be compounded by ultra-processed food (UPF). No feeding trial has evaluated UPF reduction in older adults within the framework of Dietary Guidelines for Americans (DGA). This study addressed the gap using representative omnivorous and lacto-ovo vegetarian patterns. METHODS: The secondary outcomes of the Protein-Distinct Macronutrient-Equivalent Diet 2 (PRODMED2) trial compared two DGA-aligned, low-UPF diets with each other and with a high-UPF habitual baseline (BSL) diet in 36 community-dwelling older adults. The diets featured minimally processed pork (MPP) and lentils (MPL) as representative animal- and plant-based primary proteins, each provided for 8 weeks without calorie restriction and separated by a 2-week washout. Diet compositions and intakes, body composition, cardiometabolic biomarkers, and hormones linked to nutrient sensing and energy balance were measured before and after interventions, with a subset of measures repeated at ∼1-year post-intervention follow-up (FUP). Data were primarily analyzed using robust linear mixed-effects models adjusted for covariates. RESULTS: Switching from a high-UPF BSL (∼50%E) to either low-UPF diets (∼13%E), unintentionally lowered energy intake (Δ-333 vs Δ-437 kcal/d, MPP vs MPL), resulting in reductions in body weight (Δ-3.8 vs Δ-4.4 kg), and fat mass (Δ-2.6 vs Δ-2.9 kg). Both diets improved HOMA-IR, insulin, C-peptide, total cholesterol, LDL, apolipoprotein B, non-HDL, and CRP relative to BSL (all, p < 0.038 BSL vs post-diet, no significance between diets). Fasting leptin declined (Δ-1.9 vs Δ-2.5 ng/mL MPP vs MPL) and FGF21 increased (Δ+65 vs Δ+88 pg/mL MPP vs MPL) in both diet phases (all, p < 0.026 BSL vs post-diet, no significance between diets). At FUP, as UPF exposure increased to 44 %, dietary intakes, weight, adiposity, and biomarkers returned toward BSL. CONCLUSION: Results demonstrate that low-UPF eating aligns with DGA pattern and is feasible across both plant- and animal-based diets. Both omnivorous and lacto-ovo vegetarian interventions promoted caloric reduction, weight and visceral fat loss, improved insulin sensitivity and lipid metabolism, and reduced inflammatory markers. These effects may involve nutrient sensing via FGF21 and leptin. Low-UPF diets may provide a practical approach to support healthy aging. REGISTRATION OF THE CLINICAL TRIAL: The trial is registered at www. CLINICALTRIALS: gov as NCT05581953 on October 12, 2022.