Sixty-one older men (BMI ≥ 23) completed 28 days of alternate-day fasting, randomized to calorie-matched supplements: control, leucine (0.08 g/kg), or protein (0.4 g/kg, delivering 0.04 g/kg leucine). Everyone lost fat and lean-related body composition measures, lowered systolic blood pressure, improved total and LDL cholesterol and triglycerides, and gained strength and function. Group-by-time interactions were absent for nearly every outcome; only diastolic blood pressure and HDL cholesterol differed.
The null result matters because it cuts against a popular assumption: that leucine is a shortcut for protecting muscle during calorie restriction. Mechanistic work shows leucine triggers muscle protein synthesis acutely, but acute stimulation has repeatedly failed to translate into durable lean-mass gains in trials of this kind. Several explanations fit. Four weeks is short for detecting DXA-measured muscle differences. The control group's baseline protein intake was probably already adequate, leaving little room for supplements to help. And with 61 men split three ways, the study could only detect large effects, so modest benefits cannot be excluded. The two significant interactions, among dozens of tests, deserve cautious reading as possible chance findings.
The practical takeaway: improvements in strength, blood pressure, and lipids appeared with fasting alone, even without supplements. Older adults pursuing weight loss should still prioritize adequate overall protein and resistance training, which this trial did not test. Confirmatory rather than paradigm-shifting, and a useful brake on supplement hype.