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1 Department of Nutritional Sciences Faculty of Medicine University of Toronto Toronto, Ontario Canada E-mail: randall.kaplan{at}utoronto.ca and Kunin-Lunenfeld Applied Research Unit and Department of Food and Nutrition Services Baycrest Centre for Geriatric Care Toronto, Ontario Canada
2 Rotman Research Institute Baycrest Centre for Geriatric Care Toronto, Ontario Canada and Department of Psychology Trent University Peterborough, Ontario Canada and Departments of Psychology and Psychiatry University of Toronto Toronto, Ontario Canada
3 Department of Nutritional Sciences Faculty of Medicine University of Toronto Toronto, Ontario Canada and Clinical Nutrition and Risk Modification Centre and Division of St Michael's Hospital Endocrinology and Metabolism Toronto, Ontario Canada
Dear Sir:
We agree with Das that glucose ingestion was shown to improve memory performance within 1 h of ingestion compared with a non-energy-containing placebo in a range of human and rodent populations (1). The strongest effects in humans are observed in elderly subjects and in those with existing memory deficits or relatively poor glucose regulation (2) and may be limited to declarative memory tasks (3), which are mediated by the medial temporal lobe and related structures (4). For instance, in the study that Das referred to, we found that the beneficial effects of glucose ingestion were most evident in healthy elderly subjects with normal fasting plasma glucose concentrations who had the poorest ß cell function (5). Furthermore, we extended the glucose data by showing that other carbohydrate foods could also improve memory.
Several mechanisms have been suggested to explain the effects of glucose ingestion on memory performance. Das discussed some of these and presented another potential mechanism. One common hypothesis suggests that glucose ingestion may improve memory by increasing plasma glucose concentrations, leading to alterations in glucose uptake and utilization by the brain and ultimately to an increase in the glucose-mediated synthesis of acetylcholine in the hippocampus region (6). As mentioned by Das, research with rodents supports this hypothesis (7). Others have suggested that the insulin response to an increase in glucose may be responsible for the effects on memory (8). Das suggested further that insulin may improve memory by stimulating endothelial nitric oxide formation and inhibiting the synthesis of tumor necrosis factor . Although each of these mechanisms may be involved in mediating the effects of glucose on memory, our work suggests that other mechanisms are also involved.
The important finding of our study, which Das failed to refer to, is that barley ingestion improved memory similarly to the ingestion of glucose and mashed potatoes even though it had a minimal effect on blood glucose. Although it has been commonly argued that blood glucose must increase to 810 mmol/L for memory to improve (9), we found that barley, which increased blood glucose to only 6.7 mmol/L, improved memory similarly to glucose and potatoes, which increased blood glucose to 9.5 mmol/L. In addition, although not measured, we anticipate that barley would also minimally affect insulin concentrations (10). Consequently, the aforementioned mechanisms are unlikely to account for the memory-enhancing effects of barley. Instead, our data suggest that the provision of energy, independently of elevations in blood glucose, can improve memory.
The effects of energy ingestion on gut-mediated responses could explain our findings. Several gut peptides, including cholecystokinin (11), gastrin-releasing peptide, pancreastatin, and amylin (12), influence memory in rodents, likely via stimulation of ascending fibers of the vagus nerve (11). Furthermore, electrical stimulation of the vagus in human subjects improves declarative memory (13), and vagotomy decreases the memory-enhancing effects of glucose (14) and peripherally injected drugs (11). Thus, the ingestion of any energy source may improve memory by these mechanisms, independently of elevations in blood glucose. Importantly, this mechanism does not rule out the acetylcholine or insulin hypotheses, but instead suggests that carbohydrates affect cognition by more than one mechanism. Our current work, examining the effects of protein, carbohydrate, and fat on memory performance, will increase our understanding of the effects of energy ingestion on cognition compared with the individual effects of each macronutrient.
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