Mănescu · Nutrients 2025 · narrative review · n=46 studies

Nutritional Supplements for Muscle Hypertrophy: Mechanisms and Morphology-Focused Evidence.

Cited 2 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing 46 trials without formal systematic review methodology.

PubMed 41305653 · doi:10.3390/nu17223603 · record verified 2026-08-26

What was done

This narrative review synthesized 46 eligible trials evaluating nutritional supplements for resistance training-induced muscle hypertrophy, restricting inclusion to studies measuring direct morphological outcomes (ultrasound or MRI). The review analyzed mechanisms and evidence for protein/essential amino acids (EAA), creatine monohydrate, β-hydroxy-β-methylbutyrate (HMB), and adjuncts including omega-3 fatty acids, citrulline, and collagen.

What was found

Protein/EAA supplementation consistently improved hypertrophy when daily intake was <1.6 g·kg⁻¹·day⁻¹ or per-meal leucine was <2–3 g, with benefits plateauing above ~2.0 g·kg⁻¹·day⁻¹. Creatine monohydrate (3–5 g·day⁻¹) increased muscle thickness or cross-sectional area in interventions lasting ≥8–12 weeks. HMB (3 g·day⁻¹) showed utility only under high training stress or caloric deficits, remaining neutral in well-fed, trained cohorts. Adjuncts (1–2 g·day⁻¹ omega-3, 6–8 g citrulline, 10–15 g·day⁻¹ collagen with vitamin C) supported recovery or connective tissue without driving direct hypertrophy. The abstract reports qualitative thresholds and dosing ranges but no pooled effect sizes or statistical test values.

Why it matters

It establishes a morphology-specific, tiered hierarchy for sports supplements, distinguishing agents that directly enhance muscle size (protein and creatine) from those that merely support training volume or connective tissue recovery.

Limits

The paper is a narrative rather than a systematic review or meta-analysis. The underlying evidence base is limited by methodological heterogeneity, short trial durations, inconsistent ultrasound/MRI imaging protocols, and a lack of preregistered, adequately powered studies.

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