Clinical Studies and Practice

Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention



Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD).


Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included.


Liver fat decreased after 6 months by 64% (95% confidence interval: 54–74%) in the PD group and by 43% (27–59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25–75%) in the PD group and 49% (27–71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes.


A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.

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We thank the women who participated in this study and research nurses Inger Arnesjö and Katarina Iselid for their invaluable contributions. We would like to thank Marie Eriksson of the Department of Statistics, Umeå University, Sweden, for advice on statistics, and Elin Chorell of the Department of Public Health and Clinical Medicine, Umeå University, for analyzing beta-hydroxybutyrate. This study was supported by grants from The Swedish Council for Working Life and Social Research (2006-0699 and 2010-0398), the Swedish Research Council (K2011-12237-15-6), the Swedish Heart and Lung Foundation, King Gustaf V and Queen Victoria’s Foundation, the Swedish Diabetes Research Foundation, the County Council of Västerbotten and Umeå University, Sweden.

Author contributions

JO performed the statistical analysis, interpreted the data, drafted the figure and tables and wrote the manuscript. CM recruited participants, collected the data, performed the statistical analysis and wrote the manuscript. MR recruited participants, collected the data and edited the manuscript. SS recruited participants and collected the data. JK analyzed the VAT and SAT data. CL and BL designed the study and interpreted the data. JH analyzed the liver spectroscopy data. TO designed the study, recruited participants, collected the data, interpreted the data and wrote the manuscript. All authors actively participated in revising the paper and gave approval of the final version. JO is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to J Otten.

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Otten, J., Mellberg, C., Ryberg, M. et al. Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention. Int J Obes 40, 747–753 (2016).

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