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Carbohydrates, glycemic index and diabetes mellitus

Effects on cognitive performance of modulating the postprandial blood glucose profile at breakfast



Considering the importance of glucose as a brain substrate, the postprandial rate of glucose delivery to the blood could be expected to affect cognitive functions. The purpose was to evaluate to what extent the rate of glucose absorption affected measures of cognitive performance in the postprandial period. In addition, cognitive performance was evaluated in relation to individual glucoregulation.


A white wheat bread (WWB) enriched with guar gum (G-WWB) with the capacity to produce a low but sustained blood glucose net increment was developed. The G-WWB was evaluated in the postprandial period after breakfast with respect to effects on cognitive function (working memory and selective attention (SA)) in 40 healthy adults (49–71 years, body mass index 20–29 kg/m2), using a high glycaemic index WWB for comparison in a randomised crossover design.


The G-WWB improved outcome in the cognitive tests (SA test) in the later postprandial period (75–225 min) in comparison with the WWB (P<0.01). Subjects with better glucoregulation performed superior in cognitive tests compared with subjects with worse glucoregulation (P<0.05).


Beneficial effects on cognitive performance were observed with the G-WWB in the late postprandial period. The positive effect is suggested to emanate from improved insulin sensitivity, possibly in a combination with an enhanced neural energy supply. The results highlight the importance of carbohydrate foods that induces a low but sustained blood glucose profile in enhancing postprandial cognitive functions.


The stores of glucose in the brain are limited, suggesting that the brain glucose supply may affect cognitive outcome. Studies in humans reveal that a period of intensive cognitive demand results in a measurable decline in peripheral blood glucose concentrations.1, 2 The decline in blood glucose has been suggested to be linked to increased neural energy expenditure.1, 3 Owing to instable and fluctuating glucose concentrations within the brain and an increase of brain glucose when glucose is exogenous supplied4, 5 there are several reasons to believe that peripheral glucose concentrations may affect cognitive functions, and it may in addition indicate that the postprandial rate of glucose delivered to the blood could be important in this respect. After a high glycaemic index (GI) meal, plasma glucose concentrations raise rapidly causing a high peak glucose level and a concomitant high insulin response, resulting in a rapid blood glucose disposal which in turn may cause the blood glucose level to decrease to below the fasting concentration in the later postprandial period.6 On the contrary, low-GI foods result in more moderate peak blood glucose increments, and may also maintain a prolonged net increment in blood glucose above the fasting concentration. In addition to the importance of an adequate glucose supply to the brain, a postprandial blood glucose profile characterised by a low peak but a sustained net increment of glucose above fasting concentrations may acutely improve insulin sensitivity7, 8, 9 which hypothetically may provide additional benefits on cognitive functions in the postprandial phase.10, 11 It is evident from the literature that type-2 diabetes12, 13, 14 and the metabolic syndrome15, 16 are associated with an increased risk of cognitive dysfunction. In fact, also a lowered glucose tolerance, albeit still within the normal range, is accompanied by poorer cognitive functions, for example, verbal recall, working memory (WM) capacity and vigilance, where hippocampus-dependent functions seems most vulnerable.17, 18

Studies in healthy adults investigating the postprandial effects on cognitive performance, as related to glycaemic properties of a meal, are scarce and contradictive. Some studies show beneficial effects on cognitive performance of low-GI foods,17, 19 whereas others show the opposite, no or conflicting effects.20, 21 Thus, the aim of the present study was to evaluate cognitive performance in the postprandial period after two realistic bread breakfasts resulting in profoundly different postprandial glucose responses in the early as well as in the later postprandial phase. For this purpose a white wheat bread (WWB) enriched with guar gum (G-WWB) was developed with the capacity to produce, not only a lower peak blood glucose response, but also maintain a prolonged net increment in blood glucose in the postprandial period. The G-WWB breakfast meal was evaluated in healthy adults (49–71 years, body mass index 20–29 kg/m2) using a WWB breakfast as a reference in a randomised crossover design. WM and selective attention (SA) were measured in the postprandial phase up to 240 min post breakfast. In addition, cognitive performance in the postprandial period was evaluated in relation to individual glucoregulation.

Subjects and methods

Evaluation and selection of bread products for postprandial cognitive study

In a first set of experiment, three bread products were developed, and their course of glycaemia measured and compared to that of a white wheat flour based bread (WWB, reference product) in young healthy subjects. The purpose was to select a low-GI test bread product that resulted in profoundly different course of glycaemic response compared with the WWB in the entire postprandial period, including also the later phase (120–240 min) which is beyond that used for GI calculation. Supplementary Information regarding the composition and glycaemic properties of all three test products and the WWB reference bread, respectively, is available at the EJCN website.

A low-GI test bread made from white wheat flour supplemented with guar gum (15% on dry weight basis) (G-WWB) was chosen for the cognitive study due to eliciting low increase in blood glucose concentrations in the early postprandial phase, and a low but sustained net increment in blood glucose concentration in the late postprandial phase. A WWB was used as a high-GI reference product. Both bread products were composed of the same ingredients (white wheat flour, water, salt and yeast), except for addition of guar gum in the G-WWB.

Influence of the postprandial glycaemia on cognitive function in healthy mature adults


Healthy subjects, 28 women and 12 men, aged 49–71 years (mean±s.d.: 62.9±5.0 years), with normal fasting blood glucose concentrations (5.6 mmol/l), and with body mass index in the normal to overweight range (body mass index 20–29 kg/m2, mean±s.d.=24.2±2.2) were recruited. Exclusion criteria were fasting whole-blood glucose concentrations >5.6 mmol/l. Approval of the studies was given by the Regional Ethical Review Board in Lund, Sweden (protocol 2008/5).

Study design and protocol

The study had a crossover randomised but balanced study design. Each subject served as his/her own reference and participated in the study at three separate mornings. At 2100 hours the evening before the test days, the subjects consumed a standardised evening meal.

Visit no. 1: fasting glucose concentrations and individual glucoregulation among the test subjects were determined following an overnight fast. The subjects arrived at 0800 hours and finger-prick capillary blood samples for determination of blood glucose were taken before and at 15, 30, 45, 60, 90, 120 and 150 min after a glucose drink (50 glucose in 250 ml water consumed within 5 min). The subjects performed test versions of the cognitive tests to reduce learning effects and stress during the subsequent cognitive test days.

Visit no. 2 and 3 (executions of cognitive tests, separated by at minimum 1 week): the participants arrived at 0745 hours following an overnight fast, and sat resting until 0800 hours when one of the breakfasts was served (124 g WWB or 179 g G-WWB, providing 50 g available starch), with 250 ml water. The start of the breakfast was set to zero time. Twenty subjects (6 men and 14 women) consumed the WWB breakfast on the first experimental day and the G-WWB on the second occasion (WWB/G-WWB). Consequently, 20 subjects (6 men and 14 women) had the breakfast order: G-WWB/WWB.

Cognitive tests

Working memory The tests for WM was as originally described by Daneman and Carpenter,22 requiring simultaneous storing and processing of information, but with modifications according to Radeborg et al.23 The tests consisted of 12 sets of short declarative sentences (3, 4 or 5 sentences, four of each set) that could be either semantically meaningful of the type ‘the boy brushed his teeth’, or nonsensical, such as ‘the rabbit struck the idea’. The sentences were read one by one to the subjects, and immediately after each sentence they had to indicate whether the sentence was semantically meaningful or not. The subjects were blind to the number of sentences in each set (3–5 sentences). After each set of sentences, the subjects had to repeat, in any order, the first noun in each of the sentences. Eight different but comparable WM tests were included in the study, with four WM tests included at each experimental day (performed at 90, 135, 180 and 225 min). The WM tests were given in two different orders (WM test no. 1–4 or no. 5–8), and the test order was balanced. One WM test took 8 min to perform.

Selective attention The test for SA was computerised and primarily measured the ability to sustain attention and to control and split the attention to the entire picture on the computer screen. Alike the WM test, the SA test also includes aspects of the WM. The storing time allotted was however shorter compared with the WM test, whereas the time pressure was higher. The SA test was performed as described previously,17 but instead of including 72 pictures the test included 96 pictures, each shown for 2 s on the screen. The SA test was performed at 75, 120, 165 and 210 min after start of the breakfast and was scored with the number of correct responses (total 95 credits), and for the reaction time needed to give the answer (that is, press one of the keys). In addition, the test was divided into two parts in the statistical calculations; the first half of the test (less demanding) generated at maximum 47 credits and the second half (most demanding part), at maximum 48 credits. One SA test took 10 min to perform.

Calculations and statistical methods

The influence of the WWB and G-WWB breakfast products on the cognitive tests was investigated by repeated measures analysis of variances at the test points, with order of consumption of the test meals and test meal as independent variables, and performance in WM test and SA test as dependent variables. Statistical calculations were performed in Stat View 5.0 and SuperAnova 1.11 (Abacus Concepts, Inc., Berkeley, CA, USA). The blood glucose incremental area under the curve (IAUC) 0–90 min after the 50 g glucose drink was taken as a measure of glucoregulation. GraphPad Prism (version 4.03; GraphPad Software, San Diego, CA, USA) was used for graph plotting and calculation of the areas. The median of the IAUC was determined (n=40) and the 20 subjects with an IAUC above the median were classified as with ‘worse glucoregulation’ and the 20 subjects beneath with ‘better glucoregulation’. The effects on cognitive performance of better versus worse glucoregulation (as defined) was investigated by analysis of variance with order of test meals and better versus worse glucoregulation as independent variables, and performance on cognitive tests as dependent variables. Correlations were calculated with Pearson’s correlation in MINITAB Statistical Software (release 13.32; Minitab Inc., State College, PA, USA). The significance level was set at P<0.05. The results are expressed as means±s.e.m.


Glycaemic properties of the reference and test bread products in young healthy adults

The G-WWB resulted in significantly lower postprandial incremental blood glucose area (IAUC) 0–240 min compared with the WWB (P<0.001, Figure 1). The 0–120 min IAUC following the WWB and the G-WWB were 177±25 and 72±9 mmol min/l, respectively (P<0.0001). Using the WWB as a reference (GI=100), the GI of the G-WWB was 45. In the late postprandial phase (at 210 and 240 min, respectively), the G-WWB resulted in significantly higher blood glucose concentrations compared with the WWB (P<0.01).

Figure 1

Incremental changes (Δ) in blood glucose concentrations after breakfasts composed of breads based on white wheat flour (WWB), and white wheat flour supplemented with guar gum (G-WWB). A significant treatment (type of breakfast) effect (P<0.0001) and a significant treatment × time interaction (P<0.0001) were found over the 240-min test period. The interaction revealed that the blood glucose concentrations were higher after WWB compared with G-WWB between 15 (P<0.01) and 60 min (P<0.0001 for the other test points in this interval). However, in the late postprandial phase consumption of the G-WWB resulted in higher blood glucose concentrations compared with the WWB (at 210 and 240 min, P<0.01). analysis of variance followed by Tukey’s test. The evaluation was performed in healthy young adults, n=12 (mean±s.d.: 23.1±2.3 years, body mass index: 22.1±1.5 kg/m2).

Outcome of the cognitive tests in the postprandial period after breakfast in healthy mature adults

Outcome of the cognitive tests in relation to the test products

There was a significant (breakfast × time) interaction (P<0.05) in the SA test, revealing a significantly better performance in the SA test at 120 min following the G-WWB compared with after the WWB (77.3±2.0 and 73.0±2.5 credits, respectively, P<0.01) (Table 1).

Table 1 Results in the SA tests following the complete tests and in the second half of the tests after a low-GI breakfast with a sustained net increment in glucose above the fasting value (G-WWB) or a high-GI (WWB) reference breakfasta

When only the last half of the SA test was considered (the most demanding part), the differences in cognitive performance depending on type of breakfast became more pronounced. Consequently, a main effect over the entire test period (75–235 min) was observed, showing better performance after the G-WWB breakfast compared with the WWB breakfast (SA test 1–4: 36.8±0.6 and 35.5±0.6 credits after G-WWB and WWB, respectively, P<0.01) (Table 1). There was a significant time effect in the SA tests, showing an improvement in the performance along the test period (P<0.001). There was no significant main effect depending on the order of consumption of the breakfasts (WWB/G-WWB or G-WWB/WWB), but a significant (order of consumption × breakfast) interaction was observed (P<0.001), revealing better performance during the second test day. No significant differences depending on breakfast or time were observed in reaction time (data not shown) or in the WM tests (Table 2).

Table 2 Outcome in the WM tests following a low-GI breakfast with a sustained net increment in blood glucose above the fasting value (G-WWB) or a high-GI (WWB) reference breakfasta

Outcome of the cognitive tests in relation to the individual glucoregulation

There were no significant differences in age between the subjects classified with better or worse glucoregulation (mean±s.d.: 61.9±4.4 and 64.0±5.4 years, respectively, P=0.19). Subjects with better glucoregulation performed superior in the SA test (correct responses) after the WWB compared with subjects with worse glucoregulation (SA test 1–4; P<0.05, Table 3). There were also tendencies towards better performance in the SA test in the group with better glucoregulation in the case of the G-WWB (SA test 1–4; P=0.092). Both after the WWB and after the G-WWB breakfasts, subjects with better glucoregulation showed faster reaction time (P<0.05, Table 4). Inverse correlations between blood glucose IAUC and performance in SA tests (correct responses P<0.05) and positive correlations between glucose IAUC (0–90 min) and reaction times (P<0.05) were observed after the WWB as well as after the G-WWB, indicating superior performance and faster reaction time in subjects with better glucoregulation (Table 5).

Table 3 Performance in the SA tests after the low-GI (G-WWB) and high-GI (G-WWB) test breakfasts depending on individual glucoregulationa,b
Table 4 Outcome in the SA tests measuring reaction time after the low-GI (G-WWB) and high-GI (G-WWB) test breakfasts in relation to the individual glucoregulationa,b
Table 5 Relations between glucoregulation (IAUC 0–90 min) and performance in the SA tests (correct response and reaction time)a


The G-WWB breakfast, resulting in a low postprandial blood glucose peak followed by a low but sustained net increment in glucose above the fasting value, significantly improved performance in the SA test in the later postprandial period (75–225 min) in comparison with the WWB reference breakfast, characterised by a high peak blood glucose response of short duration. Studies investigating the effects of differences in glycaemic properties of test meals on cognitive performance are scarce. In contrast to the present study, usually also other food factors in addition to absorption rate differ, for example, energy intake and macro nutrient content, making it difficult to draw conclusions regarding solely effects of the glycaemic properties of the meal.24, 25, 26

The differences in cognitive performance were observed in the later postprandial period. This finding is in concordance with our previous observations where we provided a glucose solution (glucose 50 g) to healthy volunteers through either a bolus or sipping regimen to simulate a high-GI or a low-GI breakfast, respectively.17 Consequently, the present study provide evidence that real breakfast products may affect cognition differently, linked to differences in rate of glucose delivery to the blood, and that the differences appears to be revealed in the late postprandial phase. It is noteworthy that most studies evaluating the impact of the course of glycaemia on measures of cognitive functions in the postprandial phase have mainly focused on the earlier post-meal period. However, when examining available reports, significant improvements of cognitive functions after low-GI meals predominantly occur in the later phase.17, 19, 27 Thus, the results in the present study, showing benefits on measures of cognitive function in the postprandial period between 75 and 235 min, are in concordance with other studies performed within this time frame. The present and previous studies suggest that a smoother blood glucose profile, and/or a sustained net increment in blood glucose above fasting concentrations after the G-WWB bread, may have contributed to the improved cognitive performance in the current study, meaning that the overall postprandial blood glucose profile probably is an important determinant of cognitive performance.

A glucose profile characterised by less oscillating glucose concentrations has proven beneficial with respect to acute postprandial insulin resistance.8, 9, 28 Several studies have thus shown that a breakfast meal may have effects on the glucose tolerance at the next meal (lunch), and a low but sustained increase in blood glucose concentration has proven superior in this context.8, 9, 28 Insulin and insulin receptors within the brain are important for learning and memory. Insulin resistance results in reduced insulin signalling in the brain, altering a variety of insulin-mediated events of importance for memory functions.11 Considering that insulin resistance appears to be a peripheral postprandial phenomenon,17, 19, 24, 29, 30 it can be speculated that the improvement seen in the cognitive tests after the G-WWB may be a consequence of an acutely improved insulin sensitivity within the brain. In an animal model, there was a failure in insulin resistant and obese rats to enhance plasma membrane GLUT4 translocation in hippocampus, despite elevation in plasma glucose; and no changes were found in the density of insulin receptors and in total GLUT4.31 In the same study, it was observed that cognitive functions were impaired in hippocampus depending performance. The authors concluded that insulin resistance and/or abnormal insulin receptor signalling contributed to the memory deficits observed.

The results from the present study allow us to hypothesise that negative effects on insulin receptors in the brain can occur postprandially after a single meal, for example, after a high-GI meal as opposed to the low-GI G-WWB product. However, hyperglycaemia, as may occur, for example, after a high-GI meal, is also associated with several other physiological conditions with potential negative impact on the brain; for example, increased oxidative stress,32, 33 increased inflammatory markers (IL-6)34, 35 and increased cortisol concentrations.36 In addition, acute hyperglycaemia in normal subjects may result in vasoconstriction.32 Cortisol has been shown to correlate negatively with cognitive performance, predominantly hippocampus abilities.37 Cortisol, which may promote peripheral insulin resistance, may also impair insulin signalling in hippocampus, as shown in rats, and reduce GLUT4 concentrations and translocation to hippocampal plasma membranes.38 The negative effects of cortisol in the brain can thus be suggested to result in cognitive deficits due to substrate depletion during cognitive tasks, similar to the situation in the late postprandial phase following high-GI foods.

It is well established that type-2 diabetes and the metabolic syndrome is associated with an increased risk of cognitive dysfunction.12, 13, 14, 15, 16 In the present study in a healthy subject population, subjects with better glucose regulation performed superior compared with subjects with worse glucoregulation, indicating the lack of well-defined cut-off values for the impact of glucose tolerance on cognitive performance. In the evaluation of effects of glucoregulation on cognitive functions, a median split approach was applied, dividing the subjects into two groups depending on glucoregulation as defined in the present study (IAUC). It must be noted that the reason for this approach is to categorise the subjects within the group, not to state clinical glucose intolerance.

In summary, the results in the present study indicate that a smooth postprandial blood glucose profile, as seen after the G-WWB, is superior for cognitive performance in comparison with a blood glucose profile resulting from a high-GI meal, especially in the late postprandial phase. The positive effect may emanate from improved insulin sensitivity, possibly in a combination with an enhanced neural energy supply.


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This work has been supported by the Antidiabetic Food Centre (AFC), a VINNOVA VINN Excellence Center at Lund University, Sweden.

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Correspondence to A Nilsson.

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Supplementary Information accompanies the paper on European Journal of Clinical Nutrition website

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Nilsson, A., Radeborg, K. & Björck, I. Effects on cognitive performance of modulating the postprandial blood glucose profile at breakfast. Eur J Clin Nutr 66, 1039–1043 (2012).

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  • glycaemic index
  • cognitive functions
  • working memory
  • selective attention
  • glucose tolerance
  • insulin resistance

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