British Journal of Nutrition

Full Papers

Metabolism and Metabolic Studies

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

Gerald E. Lobleya1 c1, Alexandra M. Johnstonea1, Claire Fyfea1, Graham W. Horgana2, Grietje Holtropa2, David M. Bremnera1, Iain Brooma3, Lutz Schweigera4 and Andy Welcha4

a1 Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, UK

a2 Biomathematics and Statistics Scotland, Aberdeen AB21 9SB, UK

a3 Centre for Obesity Research and Epidemiology (CORE), The Robert Gordon University, Aberdeen AB25 1HG, UK

a4 Department of Nuclear Medicine, John Mallard PET Centre, University of Aberdeen, Aberdeen AB25 9ZD, UK


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.

(Received March 05 2013)

(Revised July 30 2013)

(Accepted July 31 2013)

(Online publication September 05 2013)

Key Words:

  • Ketogenic diets;
  • Glucose kinetics;
  • Ketone body metabolism;
  • Brain;
  • Positron emission tomography


c1 Corresponding author: G. E. Lobley, fax +44 1224 716698, email


  Abbreviations: 3-OHB, 3-hydroxybutyrate; 18FDG, 18fluoro-deoxyglucose; AcAc, acetoacetate; EGP, endogenous glucose production; HP, high protein; HPLC, high-protein diets with low carbohydrate; HPMC, high-protein diets with moderate carbohydrate; M, maintenance diet; MRGlc, rate of glucose uptake by the brain; PET, positron emission tomography; Ra, rate of appearance of glucose