Alternate day fasting (ADF)

Intermittent fasting (IMF) is an alternative method of reducing energy intake (EI) that is gaining attention as a strategy for weight loss and health benefits (1)

• alternate-day fasting (ADF) is a subclass of IMF, which consists of a "fast day" (0-25% of caloric needs) alternating with a "fed day" (ad libitum food consumption)
  • ADF is a different approach to control weight than the common caloric restriction (CR) or intermittent fasting (IF) that restricts daily eating to an 8- to 12-hour window
  • evidence suggests that ADF may reduce diabetes and cardiovascular disease (CVD) risk and may favorably impact hormones involved in regulation of hunger and satiety (1)

Why 3 meals a day might not be the correct eating pattern for humans (1):

• unlike modern humans and domesticated animals
  • eating patterns of many mammals are characterized by intermittent energy intake
• carnivores may kill and eat prey only a few times each week or even less frequently
• hunter-gatherer anthropoids, including those living today, often eat intermittently depending on food availability
• ability to function at a high level, both physically and mentally, during extended periods without food may have been of fundamental importance in our evolutionary history
  • many adaptations for an intermittent food supply are conserved among mammals, including organs for the uptake and storage of rapidly mobilizable glucose (liver glycogen stores) and longer-lasting energy substrates, such as fatty acids in adipose tissue

Comparing ADF to calorific restriction:

• a small study showed that (2) ADF produced similar changes in weight, body composition, lipids and insulin sensitivity index at 8 weeks and did not appear to increase risk for weight regain 24 weeks after completing the intervention

ADF as an intervention in overweight and normal-weight individuals:

• a randomized controlled trial by Varady et al. (3) evaluated the role of ADF in losing weight in overweight and normal-weight individuals
  • subjects had a feed day alternated with a fast day with 25% of total energy intake
  • alternate day fasting group has a decrease in fat mass (P < 0.001) by 3.6 ± 0.7 kg, C-reactive protein (13 ± 17%, P < 0.05), leptin and triacylglycerol (TG) concentrations (20 ± 8%, P < 0.05), increase in low-density lipoprotein (LDL) particle size (4 ± 1, P < 0.01) and plasma adiponectin (6 ± 10%, P < 0.01) while leptin decreased (40 ± 7%, P < 0.05) when compared to the control group
  • limitations of this study were the low number of study subjects (15 patients in each group), no physical activity measurement, the possibility of under-reporting of dietary intake as the reports were taken via food records

ADF and physiological and molecular markers of ageing:

• caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well-studied
• in a randomized controlled trial study was shown that 4 weeks of strict alternate-day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average
  • initially recruited 30 participants who had followed ADF for at least 6 months before the study began and compared them to 60 healthy controls. Thirty members of the control group were then randomly assigned to ADF for 4 weeks and the other 30 participants ate whatever and whenever they wanted during that time
    • specifically, the 30 people who had followed ADF for 6 months or more and the 30 individuals randomly assigned to ADF alternated between 36 hours of not eating and 12 hours of eating whatever they wanted. These two groups were similar in terms of gender distribution, age, body mass index (BMI), and waist-to-hip ratio at baseline
      
      
• no adverse effects were seen among participants in the ADF group
  • caloric intake dropped from baseline by 37.4% (95% CI, -48.3% to -24.4%), compared with 8.2% (95% CI, -32.2% to 3.6%) in the control group
  • BMI among the 4-week fasters fell by 1.2 kg/m2 (95% CI, -1.515 to -0.875; P <.0001). The average reduction in belly fat was 14.5% ± 6.4% (P < .0001)
    
    
• ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improved the fat-to-lean ratio, and increased beta-hydroxybutyrate, even on non-fasting days
  
  
• on fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated
  • reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF

5:2 regimens diet (2 days per week of energy restriction by formula diet) in diabetes

• a study found 12 weeks diet intervention (2 days/wk energy restriction by formula diet) reduced HbA1c v lifestyle education (difference −0.34, 95% CI −0.58 to −0.11, P=0.007) (5)

Intermittent fasting (intermittent energy restriction) or continuous restriction in adolescents with obesity

• study findings showed that intermittent and continuous energy restriction delivered as part of an intensive behavioral weight management program may both be beneficial options to improve weight and cardiometabolic outcomes for adolescents (6)

Time-restricted eating (TRE) in adults with metabolic syndrome (7)

• participants were randomly assigned to standard-of-care (SOC) nutritional counseling alone (SOC group) or combined with a personalized 8- to 10-hour TRE intervention (≥4-hour reduction in eating window) (TRE group) for 3 months
• showed that compared with SOC, TRE improved HbA1c by −0.10% (95% CI, −0.19% to −0.003%)

Reference:

1. Mattson MP, Allison DB, Fontana L, Harvie M, Longo VD, Malaisse WJ, et al. Meal frequency and timing in health and disease. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(47):16647-53. doi: 10.1073/pnas.1413965111
2. Catenacci VA et al. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity (Silver Spring). 2016 Sep; 24(9): 1874-1883.
3. Varady KA, Bhutani S, Klempel MC, et al.: Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. Nutr J. 2013, 12:146.
4. Stekovic S et al. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.Cell Metab. 2019 Aug 20. pii: S1550-4131(19)30429-2
5. Jie ML et al. Effect of 5:2 Regimens: Energy-Restricted Diet or Low-Volume High-Intensity Interval Training Combined With Resistance Exercise on Glycemic Control and Cardiometabolic Health in Adults With Overweight/Obesity and Type 2 Diabetes—A Three-Arm Randomized Controlled Trial. Diabetes Care 2024; dc240241. https://doi.org/10.2337/dc24-0241
6. Lister NB, Baur LA, House ET, et al. Intermittent Energy Restriction for Adolescents With Obesity: The Fast Track to Health Randomized Clinical Trial. JAMA Pediatr. Published online August 26, 2024.
7. Manoogian ENC et al. Time-Restricted Eating in Adults With Metabolic Syndrome (https://www.acpjournals.org/doi/abs/10.7326/M24-0859): A Randomized Controlled Trial. Ann Intern Med.[Epub 1 October 2024]