Effects of a pulse-based, guidelines-aligned diet on biomarkers relevant to aging: Results from the PRODMED1 randomized controlled crossover feeding trial

BACKGROUND AND AIMS: Pulse-based diets are naturally low in methionine, an amino acid whose restriction has been linked to improved metabolic health and longevity. This study evaluated how a pulse-protein diet (PPD), relative to a meat-protein diet (MPD), both aligned with the Dietary Guidelines for Americans (DGA), influenced cardiometabolic and iron-related biomarkers relevant to aging in older adults. METHODS: This Protein-Distinct Macronutrient-Equivalent Diet 1 (PRODMED1) trial was conducted among Midwestern adults aged ≥60 years. Participants consumed MPD and PPD for eight weeks each, separated by ≥ 2-week washout. Primary protein sources (162 g/d lean pork vs. 331.6 g/d pulses) contributed ≥45% of total dietary protein. Diets were matched for total iron, energy, and macronutrients but differed in heme iron and methionine. Primary outcomes were ferritin, fasting blood glucose, and trimethylamine N-oxide (TMAO); secondary outcomes included inflammation, body composition, lipid-related cardiovascular risk biomarkers, and circulating biogenic amines. Analyses were conducted using robust linear mixed-effects models, adjusted for covariates. RESULTS: Forty-seven participants completed the trial (72% women; age 69.2 ± 6.6 years; BMI 28.6 ± 5.4 kg/m²). Regardless of protein source, both diets improved biomarkers of glucose and lipid metabolism except HDL (all, p < 0.05; no between-diet differences), while TMAO remained unchanged. Total and visceral fat mass declined (both, p < 0.0001; no between-diet differences), with a greater reduction in the visceral-to-total fat ratio during PPD vs. MPD (p < 0.05). PPD demonstrated a larger increase in ferritin relative to MPD (PPD: +15.7 ng/mL vs. MPD: +7.0 ng/mL; between-diet p = 0.027), and CRP decreased in both groups (both, p ≤ 0.001, no between-diet differences). MPD and PPD resulted in distinct circulating biogenic amine profiles (p = 0.001). CONCLUSIONS: High-quality DGA-aligned diets improved cardiovascular risk factors irrespective of primary protein sources, underscoring the importance of overall dietary-matrix quality. However, the pulse-based diet conferred additional benefits to visceral-to-total fat ratio and iron status, supporting pulses as a feasible, nutrient-dense, and effective dietary strategy with potential relevance for promoting healthspan in aging populations. CLINICAL TRIAL REGISTRY: The trial is registered at www. CLINICALTRIALS: gov as NCT05577858 on October 11, 2022.