Time-Restricted Feeding & Fasting — References

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Parent Topic: Time-Restricted Feeding & Fasting | References Hub: 01 - Foundations References MOC

Primary Literature & Landmark Studies

Citation: Sutton, E. F., Beyl, R., Early, K. S., Cefalu, W. T., Ravussin, E., & Peterson, C. M. (2018). Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metabolism, 27(6), 1212–1221.e3.
Identifiers: DOI: 10.1016/j.cmet.2018.04.010 (DOI · SciDB · Scholar) | PMID: 29754952 (PubMed · Europe PMC)
Study Design: 5-week randomized, crossover, strictly isocaloric (weight-maintaining), supervised controlled-feeding trial in men with prediabetes ( $N = 8$ ; 6-hour eTRE window with dinner before 15:00 vs. 12-hour control window).
Key Quantitative Outcomes:
- Without any weight loss, eTRE significantly increased $β$ -cell responsiveness ( $+ 14 \pm 7 U/mg, p = 0.005$ ), reduced mean 3-hour post-OGTT insulin levels by $26 \pm 9 mU/L$ ( $p = 0.001$ ), lowered morning systolic and diastolic blood pressure by $11 \pm 4 mmHg$ and $10 \pm 4 mmHg$ ( $p = 0.03$ ), and reduced plasma 8-isoprostane oxidative stress by $11 pg/mL$ (-14%, $p = 0.05$ ).

Citation: Manoogian, E. N. C., Wilkinson, M. J., O’Neal, M., Laing, K., Nguyen, J., Van, D., Rosander, A., Pazargadi, A., Gutierrez, N. R., Fleischer, J. G., Golshan, S., Panda, S., & Taub, P. R. (2024). Time-restricted eating in adults with metabolic syndrome: A randomized controlled trial. Annals of Internal Medicine, 177(11), 1462–1470.
Identifiers: DOI: 10.7326/M24-0859 (DOI · SciDB · Scholar) | PMID: 39348690 (PubMed · Europe PMC)
Study Design: 3-month parallel-group randomized controlled trial (TIMET study) in adults with metabolic syndrome and elevated $HbA_{1 c}$ or fasting glucose ( $N = 108$ ; personalized 8–10 hour TRE window vs. standard nutritional counseling).
Key Quantitative Outcomes:
- 10-hour TRE significantly reduced $HbA_{1 c}$ by $- 0.10%$ ( $95% CI [- 0.19%, - 0.003%]$ ) compared to standard care, alongside significant reductions in body weight, BMI, trunk fat mass, and visceral adiposity without loss of lean muscle mass or safety adverse events.

Citation: de Cabo, R., & Mattson, M. P. (2019). Effects of intermittent fasting on health, aging, and disease. New England Journal of Medicine, 381(26), 2541–2551.
Identifiers: DOI: 10.1056/NEJMra1905136 (DOI · SciDB · Scholar) | PMID: 31881139 (PubMed · Europe PMC)
Study Design: Landmark clinical and mechanistic review synthesizing preclinical longevity studies and human randomized trials of intermittent fasting and time-restricted feeding.
Key Quantitative Outcomes:
- Characterized the “metabolic switch” occurring 12–36 hours after cessation of food intake, wherein blood ketone levels ( $β$ -hydroxybutyrate and acetoacetate) rise from baseline $< 0.1 mM$ to $0.5-5.0 mM$ , suppressing mTOR protein synthesis and activating AMPK, SIRT1/SIRT3, PGC-1 $α$ mitochondrial biogenesis, DNA repair, and autophagic clearance.

Citation: Youm, Y. H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D’Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., Kang, S., Horvath, T. L., Fahmy, T. M., Crawford, P. A., Biragyn, A., Alnemri, E., & Dixit, V. D. (2015). The ketone metabolite $β$ -hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature Medicine, 21(3), 263–269.
Identifiers: DOI: 10.1038/nm.3804 (DOI · SciDB · Scholar) | PMID: 25686106 (PubMed · Europe PMC)
Study Design: Mechanistic immunology and metabolic study in human monocytes and murine models of NLRP3-driven autoinflammatory syndromes.
Key Quantitative Outcomes:
- Demonstrated that physiological fasting/ketogenic concentrations of $β$ -hydroxybutyrate ( $1-5 mM$ ) dose-dependently inhibit NLRP3 inflammasome activation, preventing ASC speck oligomerization and caspase-1 cleavage, and reducing IL-1 $β$ and IL-18 secretion by >60% ( $p < 0.001$ ) independent of UCP2, SIRT2, or GPR109A.