Association between Paleolithic diet fraction and systemic low-grade chronic inflammation in the Malmö diet and cancer study cohort

Purpose: The Paleolithic Diet Fraction (PDF) estimates the proportion of absolute dietary intake derived from food groups included in the Paleolithic diet. In the Malmö Diet and Cancer Study (MDCS), higher PDF and lower systemic low-grade chronic inflammation (SLGCI) have been associated with lower cardiometabolic morbidity and mortality. We examined associations between PDF and SLGCI in the MDCS. Methods: The study population (n = 23,250; 63% women; ages 44–74 years) excluded participants with prior coronary events, diabetes, stroke, high-grade inflammation, or missing baseline covariate data. PDF was calculated from baseline dietary data collected via food frequency questionnaires, seven-day food records, and interviews. Biomarkers of SLGCI included total leukocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) measured at baseline, and C-reactive protein (CRP) measured ~ 4 months later in a subpopulation (n = 4196). Results: PDF was significantly and inversely associated with all three biomarkers of SLGCI in both simple and fully adjusted models (adjusted for age, sex, physical activity level, BMI, smoking status, education level, living alone, born in Sweden, season of dietary data collection, and dietary method version): TLC (B = −0.008), NLR (B = −0.003), and lnCRP (B = −0.005), respectively (p < 0.001). Inflammatory biomarkers were weakly but significantly correlated: TLC with NLR (r_s = 0.263), TLC with CRP (r_s = 0.262), and NLR with CRP (r_s = 0.062) (p < 0.001). Conclusion: PDF was inversely associated with SLGCI biomarkers, suggesting that SLGCI may mediate its relationship with cardiometabolic outcomes. Given the cross-sectional design and CRP measurement lag, these findings should be interpreted with caution.