The Short-term Effects of Intermittent Fasting on Fat Metabolism

Intermittent fasting was shown to increase early morning fat metabolism in healthy, lean adults. 

Intermittent fasting has become a widespread dietary habit in recent years. Common types of intermittent fasting include the 16/8 method, (16 hours fasting and 8 hours for food consumption), and the 5:2 diet, where caloric consumption is only restricted two days out of the week. Intermittent fasting is associated with reduced total caloric intake and weight loss and is thought to prolong low insulin-level intervals and increase ketogenesis, among other things. It has been hypothesized that adipose tissue mobilization may be increased by extending nocturnal low insulin levels through early morning fasting: this open-label, cross-over study aimed to investigate whether early morning fasting could increase adipose tissue metabolism. 

The primary outcome measured in this study was the mobilization of adipose tissue. Adipose tissue mobilization was calculated by obtaining the AUC of β-hydroxybutyrate and free fatty acids over 6 hours. Secondary outcomes measured included gut peptide mobilization (GLP-1 and peptide Y.Y. concentrations and AUC of ghrelin) and the degree of appetite suppression and satiety induction over 6 hours. Both the degrees of appetite suppression and satiety induction were measured using visual analog scales.  

The participants of this study completed three 6-hour morning sessions after overnight fasting. Each session was held 1-3 weeks apart. The participant would either continue to fast, consume a 500 kcal Mediterranean-type breakfast, or a 500-kcal breakfast with zero carbohydrates in a randomized order. Baseline measurements were taken at the beginning of each visit, including fasting duration, FBG, fasting insulin, insulin resistance, and β-hydroxybutyrate. Measurements of plasma glucose, insulin, and visual analog scales were completed every 30 minutes for the first 120 minutes of the session, then every 60 minutes until the session was complete. Concentrations of β-hydroxybutyrate were measured via a colorimetric assay every hour.  

Participants had to be between 18 and 45 years of age and have a BMI of 18 – 25 kg/m2 to be eligible for this study. In addition, participants were excluded from the trial if they had an uncontrolled thyroid disorder, type 1 or 2 diabetes mellitus, or BMI > 25 kg/m2. Mixed linear models were used to analyze the data collected during the study. AUCs were calculated using the trapezoidal rule for all measured data.  

Ten individuals participated in this study, 70% of whom were female. The study individuals’ average age was 28.6 years, with mean BMI of 22.9 kg/m2. Linear regression showed a positive correlation between fasting duration and adjusted AUC of β-hydroxybutyrate (beta = 0.416, p = 0.018). A negative correlation was demonstrated between insulin resistance and β-hydroxybutyrate AUC (beta = -0.398, p = 0.024). After adjusting for insulin resistance and fasting duration, the measured AUC of β-hydroxybutyrate was higher following fasting sessions than the zero-carb and Mediterranean sessions (p = 0.021 and p = 0.008, respectively). 

There was no significant difference in β-hydroxybutyrate AUC measurement between the zero carb and Mediterranean-type sessions. AUC of glucose was similar across all three sessions. The AUC of insulin was significantly lower in the fasting session than in the Mediterranean session (p<0.001). The AUC of insulin was most inferior in the fasting session and highest in the Mediterranean session. The measured AUC of the hunger visual analog scales was significantly higher following fasting sessions than the zero-carb and Mediterranean sessions (p< 0.01 for both). It was not significantly different between the zero-carb and Mediterranean sessions. 

This study showed that early morning intermittent fasting could achieve lower insulin levels and more significant adipose tissue mobilization vs. zero-carb and Mediterranean-type breakfast consumption in healthy adults. Overall, the zero-carb and Mediterranean-type breakfasts were similar, though more prolonged hunger suppression was associated with the zero-carb breakfast. Although this study confirmed the prolongation of low insulin levels and mobilization of fat stores for short-term intermittent fasting, further research will be needed to assess the effects of morning fasting on long-term metabolic outcomes. 

Practice Pearls: 

• More significant fat tissue mobilization and lower insulin levels were achieved with early morning fasting in lean, healthy individuals vs. low-carb or Mediterranean breakfast. 
• Intermittent fasting resulted in the lowest hunger suppression, followed by Mediterranean breakfast. 
• Overall fat tissue mobilization and insulin levels were similar between the zero-carb and Mediterranean-type breakfasts. 

56th EASD Annual Meeting of the European Association for the Study of Diabetes. Diabetologia 63, 1–485 (2020).  

“Metabolic Effects Of Morning 16/8 Fasting – Full-Text View – Clinicaltrials.Gov”. Clinicaltrials.Gov, 2020,  

Destiny Reed, PharmD. Candidate, Florida A&M College of Pharmacy and Pharmaceutical Sciences