A summary of the crossover study on “Isolating the acute metabolic effects of carbohydrate restriction on postprandial metabolism with or without energy restriction”
Background
The study by Biyikoglu, Robertson and Collins (2025) was published in the European Journal of Nutrition in March 2025. It aimed to investigate the independent acute metabolic effects of carbohydrate restriction at varying energy levels to understand the mechanisms behind potential metabolic advantages of low-carbohydrate diets and intermittent energy restriction, independent of weight loss. The researchers sought to isolate the specific metabolic responses linked exclusively to carbohydrate reduction.
Methods
Twelve healthy overweight/obese participants completed a randomised, three-way crossover study. For one day (36 hours), covering the intervention day and overnight fasting, participants followed one of three diets, with a 5-day washout period between interventions:
- A normal carbohydrate, energy-balanced diet (nEB), serving as the control, providing 100% of estimated energy needs with 55% carbohydrate.
- A low-carbohydrate, energy-balanced diet (LCEB), providing 100% of estimated energy needs but with only 50g of carbohydrate.
- A low-carbohydrate, energy-restricted diet (LC25), providing only 25% of estimated energy needs and 50g of carbohydrate.
Protein intake was capped in the low-carbohydrate diets to avoid confounding effects.
Following each diet day, participants underwent fasting and serial postprandial measurements after consuming a standardised mixed test meal. These measurements included blood metabolites (such as glucose, insulin, triacylglycerol (TAG), non-esterified fatty acids (NEFA), 3-hydroxybutyrate (3-OHB), and GLP-1), energy expenditure, substrate utilisation (respiratory quotient – RQ), and subjective appetite responses. Subsequent two-day ad libitum food intake was also assessed.
Results
Key findings demonstrated that carbohydrate restriction, regardless of energy restriction, induced significant acute metabolic changes.
- Both low-carbohydrate diets (LCEB and LC25) resulted in a comparable decrease in postprandial TAG levels compared to the nEB diet. This finding underscores the role of carbohydrate restriction in attenuating postprandial lipaemia, a risk factor for cardiovascular disease.
- Both LC diets also led to a decrease in RQ and an increase in postprandial NEFA and 3-OHB levels. These changes are indicative of a shift towards fat oxidation and increased ketogenesis, mimicking a state similar to acute fasting.
- Compared to the nEB diet, postprandial glucose levels significantly increased in the LCEB arm and showed a rising trend in the LC25 arm. However, neither insulin responses nor measures of insulin sensitivity or β-cell function were significantly altered by the variations in energy or carbohydrate content.
- Postprandial GLP-1 levels were significantly lower in both LC arms compared to nEB. Fasting GLP-1 was higher after LC25 compared to nEB.
- While participants reported higher hunger levels on the intervention day with the LC diets, postprandial hunger was lower following both LC diets. Notably, these variations in hunger did not translate into significant differences in subsequent ad libitum food intake over two days.
- No significant changes were found in resting energy expenditure or diet-induced thermogenesis across the diets.
Conclusions
The study concludes that carbohydrate restriction alone can elicit metabolic effects similar to those observed in short-term fasting. These findings suggest that a strategy of repeated carbohydrate restriction cycles, even without energy restriction, might be an emerging alternative approach for enhancing cardiometabolic health, warranting further investigation.
Limitations include the small sample size and the focus on acute responses following a single test meal in a metabolically healthy cohort, which may have limited the statistical power for some comparisons.
References
Biyikoglu, H., Robertson, M. D., & Collins, A. L. (2025). Isolating the acute metabolic effects of carbohydrate restriction on postprandial metabolism with or without energy restriction: A crossover study. European Journal of Nutrition, 64(3), 133. https://doi.org/10.1007/s00394-025-03646-5
This post is based on Open Access research and is for informational purposes only.
