Brain Health, Cardiometabolic Health, Cognitive Decline Prevention in Robust Older Adults, Healthy Aging, Normal Aging
Conditions
Keywords
lean beef, red meat, dietary intervention, brain biomarkers, p-tau217, amyloid beta, bdnf, lipidomics, older adults, neuroprotection, nutrition, metabolomics
Brief summary
his study investigates whether eating lean beef every day can help support brain health and healthy aging in older adults. As people age, protecting memory and cognitive function becomes increasingly important. Lean beef is a rich source of essential nutrients-such as vitamin B12, iron, zinc, and creatine-that are known to support brain function. However, the direct biological effects of a beef-rich diet on brain health markers are not fully understood. In this study, researchers will recruit 20 generally healthy older adults (aged 65 and older) to participate in a dietary feeding trial. Participants will complete two separate 2-week dietary phases. During one phase, participants will consume 5.5 ounces (156 grams) of provided lean beef daily. During the other phase, they will consume an iso-caloric, protein-matched, non-beef control food daily. A two-week "washout" period, where participants return to their normal diets, will separate the two phases to ensure there are no overlapping effects. Researchers will collect blood, urine, stool, and saliva samples at the beginning and end of each 2-week dietary phase. These samples will be analyzed to see if the lean beef diet improves specific biological markers in the blood related to memory, nerve protection, and overall brain aging. Ultimately, the findings from this study will help determine if incorporating lean beef into a regular diet can be a natural, food-based strategy to help preserve neurological health in older adults.
Detailed description
Background and Rationale: Cognitive decline and related dementias represent a growing public health crisis. While age and genetics are immutable risks, diet is a key modifiable factor for prevention and resilience. Lean beef provides a unique nutrient matrix-including vitamin B12, heme iron, zinc, selenium, creatine, and choline-that may support multiple aspects of brain structure and function. Recent advances in blood-based biomarkers now allow for the sensitive detection of neuropathological processes and neuroplasticity in response to lifestyle interventions. This project seeks to move beyond observational data to uncover the biological mechanisms that confer brain health by assessing the direct molecular impact of a dietary beef intervention. Study Objectives: The overarching goal of this study is to determine the impact of regular lean beef consumption on the molecular profile of brain health in healthy older adults. The primary aim is to quantify the within-person change in plasma phosphorylated tau-217 (p-tau217) following a 2-week lean beef intervention compared to a matched non-beef control. Secondary and exploratory aims include measuring within-person changes in the amyloid-beta 42/40 ratio (Aβ42/40) and Brain-Derived Neurotrophic Factor (BDNF), characterizing global shifts in the plasma lipidome, and exploring mechanisms of action via nutrient biomarkers. Study Design: The study is designed as a two-arm, randomized, controlled, crossover feeding trial. Twenty generally healthy adults (aged 65 years and older) will be block-randomized (1:1) to begin with either the intervention phase or the control phase. Intervention Phase: Daily incorporation of 156 grams (5.5 oz) of lean beef for 14 days. Control Phase: Daily incorporation of an iso-caloric, protein-matched non-beef control for 14 days. A two-week washout period will separate the two phases to eliminate physiological carryover effects. Assignment of sequence will be randomized and counterbalanced to control for order and seasonal bias. Participants will maintain habitual eating patterns but will replace their daily protein sources with the study-provided food. Methodology and Data Collection: Clinical data and biological specimens will be collected at four distinct time points: the baseline and the conclusion of each 14-day dietary phase. At each clinical visit, fasted (12-hour) blood samples, as well as urine, stool, and saliva samples, will be collected. Basic anthropometric measurements, vital signs, and daily dietary records will also be obtained to monitor adherence and physical stability. Outcome Evaluation and Analysis: Targeted biomarkers of neurodegeneration and neuroplasticity (p-tau217, Aβ42/40, and BDNF) will be quantified using validated enzyme-linked immunosorbent assays (ELISA). Comprehensive untargeted lipidomic profiling will be conducted via Liquid Chromatography-Mass Spectrometry (LC-MS) workflows to identify lipid signatures associated with the intervention. Primary statistical analyses will utilize linear mixed-effects models to compare within-subject differences between the beef intervention and control conditions, adjusting for sequence and period effects. Appropriate statistical corrections will be applied for multiple comparisons and high-dimensional omics data.
Interventions
OTHERLean Beef
Participants will be provided with and instructed to consume 156 grams (5.5 ounces) of cooked lean beef daily for 14 days.
OTHERNon-Beef Control
Participants will be provided with and instructed to consume an iso-caloric, macronutrient- and protein-matched non-beef control consisting of a mixture of cottage cheese and whey protein daily for 14 days.
Sponsors
South Dakota State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Masking description
Due to the use of whole-food dietary interventions (lean beef vs. non-beef control), it is not possible to blind the participants or the investigators administering the diets. However, all biological specimens (blood, urine, stool, saliva) will be de-identified and coded. The outcomes assessors (laboratory personnel conducting the targeted biomarker assays and untargeted lipidomics) will remain blinded to the intervention sequence and treatment assignments during analysis.
Intervention model description
This is a 2-period, 2-treatment randomized crossover feeding trial. Participants will be randomly assigned to one of two dietary sequences: Lean Beef followed by Control, or Control followed by Lean Beef. Each dietary intervention phase lasts 14 days, separated by a 14-day washout period where participants return to their habitual diets to prevent carryover effects.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Adults aged 65 years and older. Generally healthy with no acute illnesses. Fluent in English. Willing to consume lean beef and dairy products (cottage cheese and whey protein) daily during the intervention phases. Willing to maintain current, habitual diet, physical activity levels, and body weight throughout the study. Willing to fast for 12 hours prior to clinical visits and provide blood, urine, stool, and saliva samples.
Exclusion criteria
Diagnosed with Alzheimer's disease, Parkinson's disease, or other severe cognitive disorders. History of gastrointestinal diseases (e.g., Crohn's disease, celiac disease) or major gastrointestinal surgery. Uncontrolled diabetes, severe liver or kidney disease, or a recent cardiovascular event (within the past 6 months). Allergies or severe intolerances to beef or dairy, or adherence to a strict vegetarian or vegan diet. Body weight fluctuation of \>5% within the past 3 months. Use of systemic antibiotics within the 2 months prior to baseline. Current heavy smoking or excessive alcohol consumption.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Phosphorylated Tau-217 (p-tau217) Concentration | Baseline (Day 0) and End of Intervention (Day 14) for each of the two dietary phases. | Quantitative change in fasting plasma concentrations of p-tau217, a blood-based biomarker indicative of neurodegeneration and cognitive decline. This will be measured using commercially available Enzyme-Linked Immunosorbent Assays |
| Change in Plasma Amyloid-Beta 42/40 (Aβ42/40) Ratio | Baseline (Day 0) and End of Intervention (Day 14) for each of the two dietary phases. | Quantitative change in the ratio of fasting plasma Aβ42 to Aβ40, a recognized biomarker for early amyloid pathology. This will be measured using commercially available ELISA kits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Shift in Plasma Lipidome Profile | Baseline (Day 0) and End of Intervention (Day 14) for each of the two dietary phases. | Global shifts in fasting plasma lipid species assessed via comprehensive untargeted lipidomics. Analysis will be conducted using Liquid Chromatography-Mass Spectrometry (LC-MS) workflows to evaluate relative abundance changes in lipid metabolites between the beef and control diets. |
| Change in Gut Microbiome Composition | Baseline (Day 0) and End of Intervention (Day 14) for each of the two dietary phases. | Alterations in gut microbial diversity and taxonomic relative abundance. This will be assessed via high-throughput sequencing (e.g., 16S rRNA or metagenomics) of DNA extracted from stool samples collected before and after each dietary phase. |
Countries
United States
Contacts
CONTACTSamitinjaya Dhakal, PhD
Outcome results
None listed