# Effects of Acute Iso- and Hypocaloric Carbohydrate Restriction on Liver Fat and Glucose and Lipid Metabolism

**Authors:** Amalie London, Amanda Schaufuss, Michal Považan, Marie-Louise Dichman, Jasmin Merhout, Carsten Dirksen, Sten Madsbad, Hartwig Roman Siebner, Annemarie Lundsgaard, Andreas Mæchel Fritzen, Bente Kiens, Kirstine Nyvold Bojsen-Møller

PMC · DOI: 10.1210/clinem/dgaf382 · The Journal of Clinical Endocrinology and Metabolism · 2025-07-02

## TL;DR

A low-carb, high-fat diet reduced liver fat in overweight individuals within two days, but both low-carb diets impaired glucose handling during meals.

## Contribution

Demonstrates that substituting carbohydrates with fat, without reducing calories, can lower liver fat and improve fasting metabolic markers.

## Key findings

- Liver fat decreased by 16% after a low-carbohydrate, high-fat diet compared to a control diet.
- Both low-carbohydrate diets improved fasting glucose and lipid parameters but impaired postprandial glucose handling.
- Very-low-calorie carbohydrate restriction did not reduce liver fat despite lowering fasting markers.

## Abstract

Liver fat is reduced within days after a low-carbohydrate diet substituted with fat to maintain isocaloric conditions.

Investigate the effect of matched carbohydrate restriction during isocaloric and hypocaloric conditions on liver fat and postprandial glucose and lipid metabolism.

Crossover randomized clinical trial at a research unit. Participants included 15 people with overweight/obesity (body mass index [BMI] 32.5 [31-34] kg/m2, median [IQR]). There were 3 dietary interventions: (1) 2 days of isocaloric control diet (CON), (2) 2 days of CON followed by 2 days of carbohydrate restriction (∼60 g/day) during very-low–calorie conditions (VLCDs), and (3) 2 days of CON followed by 2 days of isocaloric conditions with low carbohydrate (∼60 g/day), high-fat (LCHF) diet. Liver fat was measured using 1H-magnetic resonance spectroscopy.

Liver fat was −16% (−34; 4) (median [IQR]) after LCHF relative to after CON (P = .020), but did not differ between VLCD and CON. Fasting plasma concentrations of triacylglycerol, glucose, and insulin were lower after both LCHF and VLCD than after CON. However, postprandial plasma glucose concentrations were higher and insulinogenic index lower after both LCHF and VLCD.

Two days of LCHF led to lower liver fat, which was not observed after VLCD. This demonstrates the dynamic regulation of liver fat and the beneficial role of substituting carbohydrates with fat to maintain energy provision. Both LCHF and VLCD had positive effects on fasting parameters for glucose metabolism; however, both diets impaired early β-cell response resulting in deterioration in glucose handling during the meal test.

## Linked entities

- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** overweight (MESH:D050177), obesity (MESH:D009765)
- **Chemicals:** Fat (MESH:D005223), Glucose (MESH:D005947), Carbohydrate (MESH:D002241), Lipid (MESH:D008055), 1H (-), triacylglycerol (MESH:D014280)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12819859/full.md

## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12819859/full.md

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Source: https://tomesphere.com/paper/PMC12819859