This editorial interprets a 2026 narrative review that examined whether ketosis‑inducing diets preserve skeletal muscle during weight loss. Acute tracer studies show mechanistic effects of ketone bodies, but clinical trials of very‑low‑energy ketogenic protocols report modestly larger losses of fat‑free mass compared with non‑ketogenic regimens, likely reflecting methodological issues and the influence of protein, exercise, and energy deficit.
Study and findings
The authors performed a structured narrative search of MEDLINE up to 14 August 2026, selecting systematic reviews, meta‑analyses, randomized and prospective trials, and human tracer/biopsy studies that used a ketogenic exposure defined by carbohydrate restriction sufficient to induce nutritional ketosis (e.g., VLCKD/VLEKT). Acute human investigations demonstrated that circulating β‑hydroxybutyrate can modulate muscle protein synthesis signalling pathways (mTOR, FOXO3a) and reduce proteolysis, but these studies were short‑term and did not assess whole‑body composition.
In the clinical literature, supervised very‑low‑energy ketogenic diets (typically <800 kcal day⁻¹, protein ≈ 1.2–1.5 g kg⁻¹) produced weight loss that was largely fat mass. Comparative meta‑analyses, however, reported that the reduction in fat‑free mass (FFM) or lean body mass (LBM) was slightly greater—by a few percent—than that observed with non‑ketogenic calorie‑restricted diets. Most of these trials estimated lean tissue with dual‑energy X‑ray absorptiometry (DXA), a method sensitive to changes in glycogen and water, rather than with MRI or CT that directly quantify skeletal muscle. Consequently, the contribution of true contractile muscle loss versus loss of glycogen‑associated water remains uncertain.
Clinical interpretation
The mechanistic data suggest that ketone bodies have anabolic‑like signalling potential, yet the clinical evidence does not confirm a protective effect on contractile muscle during weight loss. The modestly larger FFM loss observed in ketogenic trials likely reflects the combined impact of severe energy restriction, variable protein intake, and the use of hydration‑sensitive body‑composition techniques. When protein intake is adequate and resistance exercise is incorporated, the difference in muscle loss between ketogenic and non‑ketogenic protocols narrows, indicating that these co‑interventions, rather than ketosis per se, are the primary determinants of muscle preservation. Therefore, for adults with obesity who choose a ketogenic approach, the current data support ensuring sufficient dietary protein and structured resistance training, while monitoring strength and functional outcomes, rather than relying on ketosis alone to spare muscle.
Limitations and open questions
Key limitations include the reliance on DXA‑derived lean estimates, which cannot separate muscle from glycogen‑bound water, and the paucity of long‑term trials that directly image skeletal muscle (MRI/CT) or assess functional performance. Most studies were short‑term (≤ 12 weeks) and involved supervised settings that may not translate to real‑world adherence. Additionally, the review did not systematically evaluate the effect of exogenous ketone supplementation, which could isolate ketosis from caloric restriction. Open questions remain regarding: (1) whether sustained ketosis with controlled protein and resistance training can achieve muscle‑preserving outcomes comparable to non‑ketogenic diets; (2) the magnitude of any ketone‑specific effect on muscle protein balance over months; and (3) how age, baseline sarcopenia, and metabolic health modify the response. Randomized controlled trials that combine MRI‑based muscle quantification, standardized protein dosing, and functional testing over longer durations are needed to resolve these issues.
Source
Caturano A, Mocini E, Titi L, Leva F, Cannavaro D, Tarsitano MG, et al. Sparing Muscle While Losing Fat: A Narrative Review of Ketogenic Diets and Lean Mass Preservation During Weight Loss. Nutrients. 2026;18(17):2933. doi: 10.3390/nu18172933. PMID: 42739105.