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Diet, Metabolism, and Disease · Journal article
Frontiers in Nutrition · September 9, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a small, uncontrolled pilot study demonstrating that a 3-month low-carbohydrate diet (60–110 g/day) in 30 adults with obesity produced significant anthropometric and metabolic improvements alongside marked proteomic changes. The study identifies distinct proteomic signatures between weight-loss responders and non-responders but lacks a control group and is underpowered to establish causation or guide clinical practice.
Single-arm pilot study with untargeted proteomics. Adults aged 18–50 years with obesity (BMI ≥ 30 kg/m²). Intervention: Low carbohydrate diet (60–110 g/day) for 3 months. n = 30.
LCD was associated with significant reductions in body weight, BMI, waist and hip circumferences, fat mass and percentage, GGT, triglycerides, and HbA1c (p < 0.001). Label-free proteomics identified 90 significantly dysregulated proteins in responders (53 upregulated, 37 downregulated) and 183 in non-responders (111 upregulated, 72 downregulated). Responder group (≥5% weight loss; n=15) showed dysregulation of TNF, IL6, IFNG, APP, DEGS1, and ENO3 related to immune response and cell signaling.
Proteomic endpoints are surrogates; no hard clinical outcomes (mortality, morbidity) measured.
This study offers a hypothesis-generating exploration of how LCD alters the plasma proteome and identifies inter-individual variability in response, but the lack of a control group and small sample prevent firm conclusions. The proteomic signatures may warrant investigation as potential biomarkers for personalizing diet intervention, but replication in a controlled design is essential before clinical application.
Single-arm, uncontrolled pilot study with small sample size (n=30) and surrogate proteomic endpoints; demonstrates feasibility of proteomics in LCD response but lacks comparator group and hard clinical outcomes.
As stated by the source record.
Quoted from the source exactly as published.
This study offers a hypothesis-generating exploration of how LCD alters the plasma proteome and identifies inter-individual variability in response, but the lack of a control group and small sample prevent firm conclusions. The proteomic signatures may warrant investigation as potential biomarkers for personalizing diet intervention, but replication in a controlled design is essential before clinical application.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Introduction Obesity is a major public health concern worldwide and contributes to multiple metabolic disorders. Low carbohydrate diets (LCDs) have been proposed as an effective strategy for weight management and metabolic improvement; however, the mechanisms underlying LCD-induced molecular changes in individuals with obesity remain incompletely understood. This study aimed to assess the impact of a three-month LCD on the proteomic profile of adults with obesity. Methods Thirty adults (18–50 years) with obesity (BMI ≥ 30 kg/m 2 ) followed an LCD (60–110 g/day) for 3 months. Anthropometric and laboratory measurements were obtained, and blood samples were collected at baseline and endpoint. Changes in the plasma proteomic profile were evaluated using an untargeted label-free quantitative proteomics approach (LC–MS/MS), complemented by bioinformatics and pathway network analyses. Anthropometric and biochemical data were analyzed using paired-sample t -tests and Wilcoxon signed-rank tests in IBM SPSS®. Results Overall, the LCD was associated with significant reductions in body weight, BMI, waist and hip circumferences, fat mass and percentage, GGT, triglycerides, and HbA1c (paired t -test, p < 0.001). Participants were stratified by total weight loss percentage into responders (≥5%; n = 15) and non-responders (<5%; n = 15). Label-free proteomics identified 90 significantly dysregulated proteins in responders (53 upregulated, 37 downregulated) and 183 in non-responders (111 upregulated, 72 downregulated) between baseline and endpoint. Significantly dysregulated proteins in the responder group included beta-enolase (ENO3) and CREG1 (both upregulated), and tenascin (downregulated). In the non-responder group, insulin-like growth factor-binding protein 7, acyl-CoA-binding protein, and talin-1 were significantly downregulated. Pathway network analysis in responders was centered around dysregulation of TNF, IL6, IFNG, APP, DEGS1, and ENO3 and was related to cell-mediated immune response, cell-to-cell signaling and interaction, and cellular movement. In non-responders, the top network was centered around PGAM1, PDIA3, PHGDH, and EGFR and was associated with cardiovascular disease, dermatological diseases and conditions, and organismal injury and abnormalities. Conclusion A three-month LCD significantly improved anthropometric and metabolic parameters in adults with obesity and was associated with marked changes in the plasma proteome. Distinct proteomic signatures between responders and non-responders highlight inter-individual variability in biological response, supporting the potential of plasma proteomics for biomarker discovery and precision nutrition in obesity management.
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