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Fructose in obesity and cognitive decline: is it the fructose or the excess energy?

  • Laura Chiavaroli1, 2,
  • Vanessa Ha1,
  • Russell J de Souza1, 2, 3,
  • Cyril WC Kendall1, 2, 4 and
  • John L Sievenpiper1, 5, 6Email author
Nutrition Journal201413:27

DOI: 10.1186/1475-2891-13-27

Received: 6 February 2014

Accepted: 24 February 2014

Published: 25 March 2014

Abstract

We read with interest the review by Lakhan and Kirchgessner, proposing that high fructose intake promotes obesity, metabolic syndrome, diabetes, and cognitive decline. Their focus on the role of fructose seems premature due to confounding from energy and the heavy reliance on low quality evidence from animal models. There is a lack of high quality evidence directly assessing the role of fructose in cognitive decline. Although one cannot exclude the possibility of a link, it remains an unconfirmed hypothesis.

Keywords

Dietary fructose Cognitive decline Obesity Energy

Letters to the Editor

Dear Editor,

We read with interest the review by Lakhan and Kirchgessner [1], proposing that high fructose intake promotes obesity and its downstrean complications including metabolic syndrome, diabetes, and cognitive decline. We feel this focus on the role of fructose is premature, as the authors did not take into consideration important confounding from energy and relied heavily on weak evidence from animal models.

Any discussion of the role of fructose in obesity and its metabolic complications must take into consideration energy intake and balance. We have published several systematic reviews and meta-analyses of controlled feeding trials in humans of the effect of fructose on cardiometabolic risk factors, demonstrating that excess calories may be the dominant factor in mediating the effects attributed to fructose. We have found that when dietary fructose is consumed in isocaloric substitution for other carbohydrate sources (that is, where the fructose arm is matched for energy to the carbohydrate comparator), there are no deleterious effects with advantages seen for glycemic control and blood pressure [28]. An overall lack of harm is true even where fructose provides excess calories (positive energy balance), as long as the carbohdyate comparator is matched for the excess calories. Fructose, however, does show adverse signals for fasting lipids in some high dose subgroup analyses [810] and for most endpoints when it provides excess calories in imbalanced hypercaloric comparisons, in which fructose supplements control diets with excess calories compared to the same diets alone without the excess calories [27]. In the absence of consistent adverse effects in isocaloric comparisons, the consistent adverse effects seen in hypercaloric comparisons suggests that excess calories are the culprit. This view is supported by other high quality systematic reviews and meta-analyses of the effect of other fructose-containing sugars [11, 12]. It is also supported by the secondary sources the authors themselves cited. Energy balance, therefore, remains an important confounder in assessing the role of fructose in obesity and its metabolic complications including cognitive decline.

One must be careful in placing too much weight on the biological plausibility provided by animal models in the fructose debate. The ability to translate these models to human physiology is limited. The majority of animal studies feed fructose at levels (typically ~60% of total energy) many fold higher than population levels of intake [13]. De novo lipogenesis, the main pathway through which fructose is thought to have its deleterious effects, also appears to be very different in animals. De novo lipogenesis from fructose accounts for 60-70% of fatty acids in rodents, while its contribution is quantitatively insignificant [13]. Two carefully conducted reviews of isotopic tracer studies showed that glucose (~50%), lactate (~25%), and glycogenesis (>15%) synthesis remain the major pathways of hepatic fructose disposal in humans, while de novo lipogenesis contributes <1% of fatty acids [14, 15]. Although fructose, more than other sources of carbohydrate, may stimulate de novo lipogenesis, its ability to do so in a meaningful way may only be seen in hypercaloric comparisons, in which fructose supplements diets with excess calories at extreme doses.

Overall, we feel that the conclusions of this review should be viewed with the appropriate caution. Where we do have higher quality evidence of the effect of fructose on cardiometabolic risk factors associated with cognitive decline, there is significant evidence of confounding from energy. There is otherwise a lack of high quality evidence directly assessing the role of fructose in cognitive decline. Although one cannot exclude the possibility of a link, it remains an unconfirmed hypothesis.

Declarations

Letter to the editor regarding

Lakhan SE and Kirchgessner A. The emerging role of dietary fructose in obesity and cognitive decline. Nutrition Journal. 2013, 12:114.

Authors’ Affiliations

(1)
Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
(2)
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto
(3)
Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University
(4)
College of Pharmacy and Nutrition, University of Saskatchewan
(5)
Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University
(6)
Li Ka Shing Knowledge Institute, St. Michael's Hospital

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Copyright

© Chiavaroli et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

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