Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate

Gerald E. Lobley, Alexandra M. Johnstone, Claire Fyfe, Graham W Horgan, Grietje Holtrop, David M. Bremner, Iain Broom, Lutz Schweiger, Andy Welch

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9 Citations (Scopus)
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Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m2, took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30 % of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An 18fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n 4) or 4 h after consumption of a test meal (n 8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-13C]acetoacetate, [2,4-13C]3-hydroxybutyrate and [6,6-2H2]glucose. The composite hunger score was 14 % lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5 % lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.
Original languageEnglish
Pages (from-to)586-597
Number of pages12
JournalBritish Journal of Nutrition
Issue number4
Early online date5 Sept 2013
Publication statusPublished - Feb 2014

Bibliographical note

The authors are grateful to Marion Scott, Jean Bryce, Nina Lanza and Kim Giles for their assistance with the preparation of the diets used in the present study. They are also grateful to Sylvia Stephen and Linda Dewar for their support in the Human Nutrition Unit.
A part of this work was supported by the Chief Scientist’s Office of the Scottish Government (grant CZG/1/131), while the remainder was funded as part of the Rural and Environment Science and Analytical Services Division core grant from the Scottish Government to the Rowett Institute of Nutrition and Health, University of Aberdeen. Neither sponsor had any role in the design and analysis of the study or in the writing of this article.


  • ketogenic diets
  • glucose kinetics
  • ketone body metabolism
  • brain
  • positron emission tomography
  • cerebral-blood-flow
  • plasma amino-acids
  • ketone bodies
  • food-intake
  • beta-hydroxybutyrate
  • acute hyperketonemia
  • ketogenic diet
  • ad-libitum
  • rat-brain


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