TL;DR: 🔴 Harm signal — high-protein enteral feeding (2.0 vs 1.3 g/kg/day) resulted in significantly WORSE quality of life with no functional benefit — directly challenges traditional high-protein guidance.
1. Publication
- Title: Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe)
- Acronym: PRECISe
- Year & Journal: The Lancet, published August 17, 2024 (404(10453):659-669)
- Citation: Bels JLM, Thiessen S, van Gassel RJJ, et al; PRECISe study team. Lancet. 2024;404(10453):659-669. doi:10.1016/S0140-6736(24)01304-7
2. Context & Rationale
Background: High protein intake (up to 2 g/kg/day) was traditionally thought beneficial during acute critical illness based on older observational data, aiming to ameliorate muscle wasting. Whether this translates into better functional recovery and quality of life had not been tested in a large, rigorous double-blind RCT.
Research Question/Hypothesis: In mechanically ventilated critically ill adults, does high enteral protein provision (2.0 g/kg/day) improve health-related quality of life and functional outcomes at 180 days compared with standard protein provision (1.3 g/kg/day)?
3. Design & Methods
- Study Type: Investigator-initiated, double-blind, multicenter, parallel-group RCT
- Setting & Centers: 5 hospitals in the Netherlands, 5 in Belgium
- Population: Mechanically ventilated critically ill adults
- Intervention: High enteral protein provision (2.0 g/kg/day)
- Comparator: Standard enteral protein provision (1.3 g/kg/day)
- Blinding: Double-blind
- Statistical Power & Follow-Up: Primary: EQ-5D-5L health-utility score during ICU stay and functional outcomes to 180 days.
4. Key Results
Outcome | High Protein (2.0 g/kg/d) | Standard Protein (1.3 g/kg/d) | Notes |
Health-related quality of life (primary) | Worse | — | High protein resulted in significantly WORSE HRQoL |
Functional outcomes at 180 days | Not improved | — | No improvement with high protein |
5. Internal Validity Assessment
Double-blind, multicenter RCT across 10 hospitals in 2 countries. Overall: Strong — rigorous double-blind design directly testing the traditional high-protein hypothesis; the clear, statistically significant HARM signal (worse HRQoL) is a genuinely important, counterintuitive finding given decades of guideline support for higher protein intake.
6. External Validity Assessment
Dutch and Belgian, 10-hospital mechanically ventilated ICU population — broadly representative of general ICU populations requiring enteral nutrition.
7. Strengths & Limitations
Strengths: Rigorous double-blind design directly challenging a long-held nutritional guideline assumption; patient-centered primary outcome (HRQoL) rather than a surrogate; joins EFFORT Protein and TARGET Protein (this handbook, 2025) as part of a now-consistent evidence pattern questioning high protein dosing.
Limitations: Two-country (though multicenter) trial; specific mechanism for the harm signal (worse HRQoL with high protein) not fully elucidated by the trial itself.
8. Interpretation & Practice Impact
Provides strong evidence that high-protein enteral feeding (2.0 g/kg/day) does NOT improve functional recovery or quality of life — and may actually be detrimental — in critically ill patients, directly challenging traditional high-protein nutritional guidance.
9. Controversies & Subsequent Evidence
An accompanying Lancet commentary ("Protein provision during critical illness") and independent commentary (NYSORA, "More Protein Is Not Better in Critically Ill Patients") both frame this as strong evidence against high-protein dosing. PRECISe joins EFFORT Protein (Lancet 2023) and TARGET Protein (JAMA 2025, this handbook's 2025 section) as three major trials now consistently failing to show benefit — or in PRECISe's case, showing harm — from higher protein provision in critical illness, a genuinely important shift in the field's evidence base. A related Bayesian meta-analysis (Heuts et al., Crit Care Med 2024) further synthesizes this evolving picture.
10. Summary & Executive Takeaway
Summary: PRECISe, a double-blind RCT across 10 Dutch/Belgian hospitals, randomized mechanically ventilated ICU patients to high (2.0 g/kg/day) or standard (1.3 g/kg/day) enteral protein. High protein resulted in significantly worse health-related quality of life and did not improve functional outcomes at 180 days.
Overall Takeaway: High-protein enteral feeding does not improve, and may worsen, quality of life and functional recovery in critically ill patients — a genuinely important challenge to traditional high-protein nutritional guidelines, now reinforced by a consistent pattern across PRECISe, EFFORT Protein, and TARGET Protein (this handbook) all failing to demonstrate benefit from higher protein dosing.
11. Bibliography
- Heyland DK, Patel J, Compher C, et al; EFFORT Protein Investigators. Lancet. 2023;401(10376):568-576.
- Summers MJ, Chapple LS, Karahalios A, et al. TARGET Protein. JAMA. 2025;334(4):319-328 (this handbook, 2025 GI/Nutrition category).
- Heuts S, Lee ZY, Lew CCH, et al. Higher versus lower protein delivery in critically ill patients: Bayesian meta-analysis. Crit Care Med. 2024;53:e645-e655.