Fructose-Containing Sugars, Blood Pressure, and Cardiometabolic Risk: A Critical Review
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Excessive fructose intake from high-fructose corn syrup (HFCS) and sucrose has been implicated as a driving force behind the increasing prevalence of obesity and its downstream cardiometabolic complications including hypertension, gout, dyslidpidemia, metabolic syndrome, diabetes, and non-alcoholic fatty liver disease (NAFLD). Most of the evidence to support these relationships draws heavily on ecological studies, animal models, and select human trials of fructose overfeeding. There are a number of biological mechanisms derived from animal models to explain these relationships, including increases in de novo lipogenesis and uric acid-mediated hypertension. Differences between animal and human physiology, along with the supraphysiologic level at which fructose is fed in these models, limit their translation to humans. Although higher level evidence from large prospective cohorts studies has shown significant positive associations comparing the highest with the lowest levels of intake of sugar-sweetened beverages (SSBs), these associations do not hold true at moderate levels of intake or when modeling total sugars and are subject to collinearity effects from related dietary and lifestyle factors. The highest level of evidence from controlled feeding trials has shown a lack of cardiometabolic harm of fructose and SSBs under energy-matched conditions at moderate levels of intake. It is only when fructose-containing sugars or SSBs are consumed at high doses or supplement diets with excess energy that a consistent signal for harm is seen. The available evidence suggests that confounding by excess energy is an important consideration in assessing the role of fructose-containing sugars and SSBs in the epidemics of hypertension and other cardiometabolic diseases.
KeywordsFructose Sugars Sugar-sweetened beverages Cardiometabolic risk Obesity Blood pressure Hypertension Uric acid Gout Dyslipidemia Non-alcoholic fatty liver disease (NAFLD) Cardiovascular risk
Aspects of this work were funded by a Canadian Institutes of Health Research (CIHR) Knowledge Synthesis grant (funding reference number, 102078) and a research grant from the Calorie Control Council. Vanessa Ha and Adrian Cozma were supported by Province of Ontario Graduate Scholarships. Russell J de Souza was funded by a CIHR Postdoctoral Fellowship Award. None of the sponsors had a role in any aspect of the present study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Compliance with Ethics Guidelines
Conflict of Interest
Vaness Ha and Arash Mirrahimi have received research support from the CIHR.
Viranda H. Jayalath and Adrian I. Cozma declare that they have no conflict of interest.
Russell J. de Souza has received research support from CIHR, Calorie Control Council, and The Coca-Cola Company (investigator initiated, unrestricted grant). He has also served as an external resource person to the World Health Organization's (WHO) Nutrition Guidelines Advisory Group (NUGAG), and was the lead author of a systematic review and meta-analysis commissioned by the WHO of trans fatty acids and health outcomes. The WHO paid for his travel and accommodation to attend the 5th NUGAG Meeting in Hangzhou, China (4–7 March, 2013).
John L. Sievenpiper has received research support from CIHR, Calorie Control Council, The Coca-Cola Company (investigator initiated, unrestricted grant), Pulse Canada, and The International Tree Nut Council Nutrition Research & Education Foundation. He has received travel funding, speaker fees, and/or honoraria from the American Heart Association, American Society for Nutrition (ASN), National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, Canadian Diabetes Association, Calorie Control Council, Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, International Life Sciences Institute (ILSI) North America, ILSI Brazil, Abbott Laboratories, Pulse Canada, and The Coca-Cola Company. He is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of both the CDA and EASD, as well as the ASN writing panel for a scientific statement on the metabolic and nutritional effects of fructose, sucrose and high fructose corn syrup. His wife is an employee of Unilever Canada.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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