STRONG Trial Tests Blueberries, Protein and Exercise Against Frailty in Older Adults

Frailty and cardiovascular disease feed each other. Frail older adults face higher risks of stroke, heart failure complications, hospitalization and death, even without a prior heart diagnosis. Shared drivers such as chronic inflammation and oxidative stress may explain the overlap. This BMJ Open protocol describes a trial of whether a simple, low-cost, multidomain lifestyle package can reduce frailty and improve heart health together. It is a protocol paper, so no outcome data have been reported.

STRONG is a pragmatic, parallel-group, superiority randomized controlled trial in community-dwelling adults aged 65 and older in Nova Scotia, Canada. The team plans to enroll 240 participants, randomized 1:1 to the intervention or usual care, with 60 women and 60 men per arm. The intervention lasts 12 months, followed by a further year of observation. Eligibility is deliberately broad: age 65 or older and willingness to do low-to-moderate exercise. All medications are permitted. Enrollment was planned to begin in December 2025.

The intervention adds three components to usual care: 30 g/day of whey protein isolate (about 25 g of protein), 1 cup (150 g) of blueberries daily, usually frozen wild, and three 60-minute individualized sessions weekly with a clinical exercise physiologist. Sessions combine 30-45 minutes of resistance training with 5-20 minutes of aerobic work, and effort is tracked on a 10-point perceived-exertion scale. The doses are evidence-informed. A prior 6-month trial found 1 cup of blueberries improved endothelial function, arterial stiffness and HDL cholesterol in older adults with metabolic syndrome, while half a cup had no effect. A meta-analysis found whey lowered IL-6 only at 30 g/day or more.

Primary outcomes span three domains. Frailty is measured by a deficit-accumulation frailty index, the Clinical Frailty Scale and the Pictorial Fit-Frail Scale. Cardiovascular risk covers lipids, blood pressure, Reynolds and Framingham scores, and echocardiographic ejection fraction and global longitudinal strain. Inflammation is measured by IL-1β, TNFα, IL-6 and IL-10. Secondary outcomes include the 6-minute walk test, grip strength, sit-to-stand, balance, diet quality, household food work and quality of life. Assessments occur at baseline and 12 months, with many repeated at 3, 6, 9 and 24 months. The team will test whether effects differ by sex and are mediated by inflammation.

The sample size was set for 80% power. About 180 participants can detect a 0.07 change in frailty index (SD 0.1) and a 0.26 mmol/L HDL difference (SD 0.41). About 220 are needed for IL-6. The target of 240 allows for 8% loss to follow-up or non-adherence. Randomization uses sex-balanced blocks managed by a third-party biostatistician. The analysis team and sonographers will be blinded, but participants and exercise staff cannot be. Analyses will be intention-to-treat and per-protocol, with adherence defined as roughly 70% of nutrition doses and 70% of workouts.

The authors note that diet adherence relies on self-report and cannot be verified perfectly. Participants may tire of daily blueberries and protein, and attending three weekly sessions for a year may be difficult. Because the intervention is a bundle tested against usual care, it cannot show which component drives any benefit. The trial is funded by the River Philip Foundation.