Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity
Monda A, Casillo M, Allocca S, Moscatelli F, La Marra M, Monda V, Di Maio G, Vasco P, Monda M, Polito R, Messina G, Messina A
Nutrients · 2 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
Según la declaración de financiación del texto completo.
Publicación
- Publicado
- 2026-01-12 · Nutrients · vol. 18 · número 2 · pág. 238
- Editorial
- Multidisciplinary Digital Publishing Institute
- Citado
- 2 citas · más que el 95% de estudios similares · 8.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 41 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Dietary Effects on Health · Diet and metabolism studies · Regulation of Appetite and Obesity
- Palabras clave
- obesity, ketogenic diet, intermittent fasting, time-restricted eating, alternate-day fasting, orexin-A, neuroendocrine adaptation, metabolic flexibility, inflammation, inflammatory cytokines, body composition, fat mass, fasting blood glucose, lipid profile, dietary adherence
- MeSH
- humans, obesity, blood glucose, body mass index, fasting, body composition, adult, middle aged, female, male, orexins, diet, ketogenic, intermittent fasting
12 autores
- Antonietta Monda🇮🇹San Raffaele University of Rome
- Maria Casillo🇮🇹University of Campania "Luigi Vanvitelli"
- Salvatore Allocca🇮🇹University of Campania "Luigi Vanvitelli"
- Fiorenzo Moscatelli🇮🇹Pegaso University
- Marco La Marra🇮🇹University of Campania "Luigi Vanvitelli"
- Vincenzo Monda🇮🇹Parthenope University of Naples
- Girolamo Di Maio🇮🇹Pegaso University
- Paride Vasco🇮🇹University of Foggia
- Marcellino Monda🇮🇹University of Campania "Luigi Vanvitelli"
- Rita Polito🇮🇹 · autor de correspondenciaPegaso University
- Giovanni Messina🇮🇹University of Campania "Luigi Vanvitelli"
- Antonietta Messina🇮🇹University of Campania "Luigi Vanvitelli"
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background/objectives
Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity.
Methods
In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m2) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex.
Results
All participants completed the intervention. The ketogenic diet produced the largest sustained reductions in BMI, fat mass, fasting glucose, and total cholesterol over 12 months. TRF16:8 elicited more rapid early metabolic improvements and showed the most consistent longitudinal increase in Orexin-A levels. The ADF5:2 protocol resulted in moderate improvements across outcomes. In all groups, increases in Orexin-A were associated with markers of improved metabolic flexibility and reduced inflammation; however, mediation analyses were exploratory and non-causal. Between-group differences remained significant for fat mass, glucose, and Orexin-A trajectories after correction for multiple comparisons.
Conclusions
The ketogenic diet was associated with the most pronounced long-term metabolic improvements, whereas 16:8 time-restricted eating yielded faster early responses and the most stable enhancement in Orexin-A levels. These findings indicate distinct metabolic and neuroendocrine adaptation profiles across dietary strategies. Given the small sample size, results should be interpreted cautiously, and larger trials are warranted to clarify the role of Orexin-A as a potential biomarker of dietary response in obesity.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.