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Impact of a whole food, plant-based diet on LDL-cholesterol and cardiovascular risk factors in adults with heterozygous familial hypercholesterolemia: a randomized, two-period, two-treatment, crossover, fully controlled feeding trial.

Source: PubMed, NCBI / U.S. National Library of Medicine

Nature communicationsLessard-Lord Jacob, Guay Valérie, Rancourt-Bouchard Maryka, et al.Published 5/20/2026Last synced 5/25/2026Status: syncedPMID: 42161961DOI: 10.1038/s41467-026-73468-4

Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder that accelerates atherosclerosis and leads to premature cardiovascular diseases (CVD). Whole food, plant-based diets (WFPB) are recommended worldwide for their cardioprotective properties but evidence regarding their effects in HeFH management remains unavailable. This study aims to evaluate the impact of a WFPB, in place of a standard American diet (SAD), on LDL-cholesterol (LDL-C) (primary outcome) and other CVD risk factors among adults with HeFH. In this randomized, two-period, two-treatment, crossover, controlled feeding trial, 50 adults with genetically confirmed HeFH, free of cholesterol-lowering medication, consumed a WFPB and a SAD for 4 weeks each in a random order, under fully controlled, isocaloric feeding conditions. The diets were separated by a two- to four-week washout period. LDL-C and other CVD risk factors were measured at the end of each diet. The WFPB induced a clinically significant reduction in LDL-C relative to the SAD (&#x2009;-&#x2009;17.9%, 95% CI: -21.7%, -14.3%; P&#x2009;<&#x2009;0.0001). The study demonstrates the clinical significance of diet therapy in HeFH and supports its re-establishment as a cornerstone in clinical guidelines (clinicaltrials.gov registration: NCT05181553; funding: Canadian Institutes of Health Research).

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