Abstract

Background Popular dietary patterns for cardiovascular and cognitive health such as the Mediterranean and MIND diets emphasize plant-based foods while limiting red meat intake. However, most research combines processed and unprocessed forms, limiting conclusions about unprocessed red meat.

Objective To evaluate the effects of incorporating minimally processed lean red meat into a nutrient-dense, plant-forward, healthy dietary pattern on markers of aging-associated health decline.

Methods This 18-week all-food-provided randomized controlled crossover feeding PRODMED2 trial tested an omnivorous red meat diet with 162g/d minimally processed pork (MPP) against a macronutrient- and energy-matched no-meat control diet with minimally processed lentils (MPL). Serum biomarkers relevant to metabolic-related cognitive and physical health were explored in 36 adults aged ≥65 years. Primary and secondary endpoints included five cardiovascular-related markers, 12 nutrition- and neurotransmitter-related measures, two metrics of body composition, and two muscular fitness outcomes. Data was analyzed using robust mixed effects models adjusted for covariates.

Results Intervention diets were well tolerated, with high adherence. Improvements in cognitive related metabolic biomarkers were observed across both arms. Fasting insulin declined more after MPP (p < 0.001), with a corresponding increase in SPISE (p = 0.032), though between-group differences were not significant. HDL was higher post-MPP than post-MPL (p = 0.034). Body weight decreased in both arms (p < 0.05), with a smaller lean mass loss trend following MPP. Grip strength and chair-rise performance were maintained. Neuroactive metabolites and bioactive amino acid profiles shifted favorably in both arms.

Conclusion These findings challenge the perception that red meat is broadly unsuitable for older adults. Including familiar foods like red meat, particularly in minimally processed form and within a healthy overall dietary pattern, may provide age-associated health benefits and improve adherence to plant-forward diets. These results have important implications for healthspan of older U.S. populations where red meat remains popular.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT05581953

Clinical Protocols

https://cdn.nutrition.org/article/S2475-2991(25)00048-4/fulltext

Funding Statement

This work was funded by the National Pork Checkoff, Meat Foundation, and the USDA NIFA/AES.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The trial was registered at ClinicalTrials.gov (NCT05581953) and was approved by the Institutional Review Board at South Dakota State University (IRB #2209010-EXP). Work was carried out in accordance with the Declaration of Helsinki, and all participants provided written informed consent. Detailed information regarding the overall study design and recruitment protocols has been previously published (de Vargas et al., 2025, Current Developments in Nutrition)

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data availability

Data is available upon reasonable request by contacting the corresponding author.

AbbreviationsADAlzheimer’s diseaseASCVDatherosclerotic cardiovascular diseaseBDNFbrain-derived neurotrophic factorBMIbody mass indexcognometaboliccognitive-related metabolic healthDGADietary Guidelines for AmericansDXAdual-energy X-ray absorptiometryGABAgamma-aminobutyric acidHDLhigh-density lipoproteinMPLminimally processed lentilMPPminimally processed porkRCTrandomized controlled trialSPISEsingle-point insulin sensitivity estimator.