SCIENCE  |  NUTRITION 

Fasting, particularly intermittent fasting (IF), has garnered attention for its potential benefits on longevity and overall health. Research suggests that fasting can enhance metabolic health, promote cellular repair, and increase lifespan by triggering mechanisms such as autophagy and reducing inflammation.

Key Concepts:

  1. Autophagy: Fasting induces autophagy, a cellular process that removes damaged cells and proteins, which is linked to increased longevity and reduced risk of age-related diseases.
  2. Metabolic Health: Fasting improves insulin sensitivity, reduces oxidative stress, and lowers risk factors for chronic diseases like cardiovascular disease and type 2 diabetes.
  3. Gene Expression: Fasting can influence the expression of longevity-related genes, such as Klotho, which is associated with improved cognitive function and increased lifespan.
  4. Circadian Rhythms: Time-restricted feeding aligns eating patterns with circadian rhythms, which may enhance the benefits of fasting by optimizing metabolic processes and improving overall health.
In summary, fasting and related dietary strategies offer promising avenues for extending healthy lifespan and improving various aspects of metabolic health.

International consensus on fasting terminology

PUBLICATIONS

  1. The effects of intermittent fasting on body composition and cardiometabolic health in adults with prediabetes or type 2 diabetes: A systematic review and meta-analysis.
          • Diabetes Obes Metab. 2024 Sep;26(9):3830-3841. doi: 10.1111/dom.15730. Epub 2024 Jul 2.
          • Design: Systematic review and meta-analysis comparing intermittent fasting (IF) with control diet and/or calorie restriction on body composition and cardiometabolic health in individuals with prediabetes and type 2 diabetes.
          • Summary: IF was found to be effective for weight loss and improving specific cardiometabolic markers, such as body weight, BMI, and certain lipid levels, in adults with prediabetes or type 2 diabetes. It did not significantly affect other markers like fat mass or insulin levels compared to control diets.
  2. The Effect of Time-Restricted Eating Combined with Exercise on Body Composition and Metabolic Health: A Systematic Review and Meta-Analysis.
          • Adv Nutr. 2024 Aug;15(8):100262. doi: 10.1016/j.advnut.2024.100262. Epub 2024 Jun 17.
          • Design: Systematic review and meta-analysis evaluating the efficacy of time-restricted eating combined with exercise compared with control diets and exercise.
          • Summary: TRE combined with exercise was more effective in reducing body weight, fat mass, and improving certain lipid profiles compared to control diets with exercise. However, it did not show additional benefits for glucose profile and some other lipid measures.
  3. The optimal time restricted eating interventions for blood pressure, weight, fat mass, glucose, and lipids: A meta-analysis and systematic review.
          • Trends Cardiovasc Med. 2024 Aug;34(6):389-401. doi: 10.1016/j.tcm.2023.10.002. Epub 2023 Oct 12.
          • Design: Meta-analysis and systematic review assessing the effects of optimal time-restricted eating interventions on cardiovascular risk factors.
          • Summary: TRE significantly reduced systolic blood pressure, body weight, BMI, fat mass, and blood glucose levels. Optimal TRE interventions varied based on the target outcome and population characteristics, suggesting tailored approaches for different health benefits.
  4. Adverse events profile associated with intermittent fasting in adults with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials.
          • Nutr J. 2024 Jul 10;23(1):72. doi: 10.1186/s12937-024-00975-9.
          • Design: Systematic review and meta-analysis evaluating the adverse events associated with intermittent fasting in adults with overweight or obesity.
          • Summary: Intermittent fasting was not associated with significantly increased risks of common adverse events such as fatigue or headache compared to control groups. A higher risk of dizziness was noted in some subgroups, but overall, IF did not show a higher risk of adverse events.
  5. Breakfast skipping and risk of all-cause, cardiovascular and cancer mortality among adults: a systematic review and meta-analysis of prospective cohort studies.
          • Food Funct. 2024 Jun 4;15(11):5703-5713. doi: 10.1039/d3fo05705d.
          • Design: Systematic review and meta-analysis assessing the association between breakfast skipping and mortality outcomes.
          • Summary: Skipping breakfast was associated with a higher risk of all-cause, cardiovascular, and cancer mortality compared to regular breakfast consumption. Findings suggest the importance of maintaining regular breakfast habits for overall health and longevity, though results may vary by study quality and geographic factors.
  6. Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity: A Randomized Controlled Trial
          • Ann Intern Med. 2024 May;177(5):549-558. doi: 10.7326/M23-3132. Epub 2024 Apr 19.
          • Design: Randomized, isocaloric feeding study.
          • Summary: This study investigated the effect of time-restricted eating (TRE) versus a usual eating pattern (UEP) on body weight in adults with obesity and prediabetes or diet-controlled diabetes, in a setting of stable caloric intake. Both groups had isocaloric diets but different eating windows. Results showed that TRE did not produce significant differences in weight loss compared to UEP after 12 weeks, suggesting prior weight loss in TRE studies may be due to reduced caloric intake.
  7. Effects of 3 Months of 10-h per-Day Time-Restricted Eating and 3 Months of Follow-up on Bodyweight and Cardiometabolic Health in Danish Individuals at High Risk of Type 2 Diabetes: The RESET Single-Centre, Parallel, Superiority, Open-Label, Randomised Controlled Trial
          • Lancet Healthy Longev. 2024 May;5(5):e314-e325. doi: 10.1016/S2666-7568(24)00028-X. Epub 2024 Apr 5.
          • Design: Single-centre, parallel, superiority, open-label randomized controlled trial.
          • Summary: This study assessed the effects of 3 months of 10-hour per-day TRE and a follow-up period on body weight and cardiometabolic health in high-risk individuals for type 2 diabetes. No significant difference in body weight was found between the TRE group and the control group after 3 months, although there was a slight weight loss in the TRE group during the intervention period. The follow-up period showed no lasting effects.
  8. Intermittent Fasting and Longevity: From Animal Models to Implications for Humans
          • Ageing Res Rev. 2024 Apr;96:102274. doi: 10.1016/j.arr.2024.102274. Epub 2024 Mar 17.
          • Design: Review article.
          • Summary: This review discusses intermittent fasting (IF) and its potential as a strategy to extend lifespan and address age-related issues. The review covers findings from animal models and human studies, highlighting how IF can optimize energy utilization, improve physiological function, and slow aging and disease processes.
  9. Circadian Alignment of Food Intake and Glycaemic Control by Time-Restricted Eating: A Systematic Review and Meta-Analysis
  10. Prolonged Fasting Outperforms Short-Term Fasting in Terms of Glucose Tolerance and Insulin Release: A Randomised Controlled Trial
          • Br J Nutr. 2023 Nov 14;130(9):1500-1509. doi: 10.1017/S0007114523000557. Epub 2023 Mar 3.
          • Design: Randomized controlled trial.
          • Summary: This study compared prolonged fasting (6 days) with short-term fasting (2 days) in terms of glucose tolerance and insulin release. Prolonged fasting resulted in greater increases in ketone levels and improvements in glucose tolerance compared to short-term fasting, suggesting a longer fasting duration may be more beneficial for metabolic health.
  11. Meal Skipping and Shorter Meal Intervals Are Associated with Increased Risk of All-Cause and Cardiovascular Disease Mortality among US Adults.
          • J Acad Nutr Diet. 2023 Mar;123(3):417-426.e3.
          • Design: Prospective study on meal frequency, skipping, and intervals in relation to mortality.
          • Summary: Eating one meal per day and skipping breakfast are associated with increased mortality risk. Shorter meal intervals between meals are linked to higher all-cause mortality.
  12. Metabolic Efficacy of Time-Restricted Eating in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
          • J Clin Endocrinol Metab. 2022 Nov 25;107(12):3428-3441.
          • Design: Systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of TRE.
          • Summary: TRE significantly reduces body weight and fat mass, particularly in overweight individuals, and has beneficial effects on lipid profiles.
  13. Association of Prolonged Nightly Fasting with Cardiovascular, Renal, Inflammation, and Nutritional Status Biomarkers in Community-Dwelling Older Adults.
          • Am J Clin Nutr. 2022 May 1;115(5):1282-1289.
          • Design: Cross-sectional analysis assessing the association between prolonged nightly fasting and various biomarkers.
          • Summary: Prolonged nightly fasting did not show beneficial associations with biomarkers and was associated with some modest detrimental effects in older adults.
  14. Intermittent Fasting versus Continuous Calorie Restriction: Which Is Better for Weight Loss?
          • Nutrients. 2022 Apr 24;14(9):1781.
          • Design: Systematic review and meta-analysis comparing intermittent fasting and continuous calorie restriction.
          • Summary: Intermittent fasting was found to be superior to continuous calorie restriction for weight loss, with significant body weight reduction but no difference in BMI.
  15. Time-Restricted Feeding Modulates the DNA Methylation Landscape, Attenuates Hallmark Neuropathology and Cognitive Impairment in a Mouse Model of Vascular Dementia.
          • Theranostics. 2022 Mar 21;12(7):3007-3023.
          • Design: Study on the effects of time-restricted feeding on DNA methylation, neuropathology, and cognitive impairment in a mouse model of vascular dementia.
          • Summary: Time-restricted feeding improved cognitive function and reduced neuropathological changes in a mouse model, suggesting potential benefits in mitigating vascular dementia.
  16. Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho
          • Mol Psychiatry. 2021 Nov;26(11):6365-6379
          • Design: Comparison of intermittent fasting (IF) vs. daily calorie restriction (CR) and ad libitum conditions in mice
          • Summary: IF improved long-term memory and adult hippocampal neurogenesis in mice more effectively than 10% daily CR. IF upregulated the longevity gene Klotho in the hippocampus, enhancing memory and neurogenesis.
  17. Circadian autophagy drives iTRF-mediated longevity
          • Nature. 2021 Oct;598(7880):353-358
          • Design: Study on intermittent time-restricted feeding (iTRF) and its effects on lifespan and autophagy in Drosophila
          • Summary: iTRF extended lifespan and delayed ageing markers in Drosophila. Circadian-regulated autophagy was identified as a key factor in the lifespan extension mediated by iTRF.
  18. The influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans: A systematic review and meta-analysis
          • Clin Nutr. 2021 Apr;40(4):1811-1821
          • Design: Systematic review and meta-analysis of fasting and energy-restricted diets on leptin and adiponectin levels
          • Summary: Fasting and energy-restricted diets significantly reduced leptin levels. Energy restriction of ≤50% normal intake increased adiponectin levels. No significant effect on adiponectin from fasting alone was observed.
  19. Association between skipping breakfast and risk of cardiovascular disease and all cause mortality: A meta-analysis
          • Clin Nutr. 2020 Oct;39(10):2982-2988
          • Design: Meta-analysis of studies on skipping breakfast and its association with cardiovascular disease and all-cause mortality
          • Summary: Skipping breakfast was associated with increased risk of cardiovascular disease and all-cause mortality. Regular breakfast consumption may improve cardiovascular health and reduce mortality risk.
  20. Unravelling the health effects of fasting: a long road from obesity treatment to healthy life span increase and improved cognition
          • Ann Med. 2020 Aug;52(5):147-161
          • Design: Review of health effects of fasting and different fasting patterns
          • Summary: Fasting activates metabolic switches from glucose to ketones, improves cognition, extends life span, and enhances defences against oxidative and metabolic stresses. Various fasting protocols contribute to these benefits.
  21. Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota.
          • Cell Metab. 2017 Oct 3;26(4):672-685.e4.
          • Design: Study on mice evaluating the effects of every-other-day fasting (EODF) on white adipose tissue browning and obesity through gut microbiota modulation.
          • Summary: EODF stimulates the development of beige fat in white adipose tissue, improving obesity, insulin resistance, and hepatic steatosis. This effect is mediated by changes in the gut microbiota, leading to increased fermentation products like acetate and lactate, which activate beige fat and enhance metabolic homeostasis.
  22. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression
          • Cell Stem Cell. 2014 Jun 5;14(6):810-23
          • Design: Study on prolonged fasting and its effects on IGF-1/PKA signaling, hematopoietic stem cell regeneration, and immunosuppression
          • Summary: Prolonged fasting reduced IGF-1 and PKA activity, promoting stem cell regeneration and reversing age-related immunosuppression. Fasting cycles alleviated chemotherapy-induced immunosuppression in mice.
  23. Intermittent fasting promotes bacterial clearance and intestinal IgA production in Salmonella typhimurium-infected mice.
          • Scand J Immunol. 2014 May;79(5):315-24.
          • Design: Study comparing the impact of intermittent fasting versus ad libitum feeding on bacterial clearance and intestinal IgA production in S. typhimurium-infected mice.
          • Summary: Intermittently fasted mice had lower bacterial loads and higher IgA levels compared to ad libitum-fed mice, suggesting intermittent fasting enhances resistance to S. typhimurium infection by promoting IgA production and pathogen elimination.
  24. Short-term fasting induces profound neuronal autophagy.
          • Autophagy. 2010 Aug;6(6):702-10.
          • Design: Study investigating the effects of short-term fasting on autophagy in cortical neurons and Purkinje cells in mice.
          • Summary: Short-term fasting led to a significant increase in neuronal autophagy, shown by the rise in autophagosome abundance and a reduction in neuronal mTOR activity. These findings suggest that intermittent fasting may have therapeutic potential in neuroprotection by promoting autophagy in the brain.
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