Portal de Periódicos da CAPES

Fructose, Obesity, and Related Epidemiology

2010; Taylor & Francis; Volume: 50; Issue: sup1 Linguagem: Inglês

10.1080/10408398.2010.526870

1549-7852

Geoffrey Livesey,

Liver Disease Diagnosis and Treatment

Fructose occurs in fruits, vegetable, and sweetened drinks alongside glucose as free sugars or bound in sucrose, but may also be bought in a pure form. A link between sugar-sweetened drinks (SSD) and body mass index (BMI, kg/m2) is inferred from systematic reviews of both prospective cohort studies (PCSs) and randomized, controlled trials (RCTs) (Malik et al., 2006 Malik, V. S., Schulze, M. B. and Hu, F. B. 2006. Intake of sugar-sweetened beverages and weight gain: a systematic review. Am. J. Clin. Nutr., 84: 274–288. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Wolf and Dansinger, 2008 Wolf, E. and Dansinger, M. L. 2008. Soft drinks and weight gain: How strong is the link?. Medscape J. Med., 10: 189–196. [Google Scholar]). The link is seemingly strong because such studies rank highly among types of studies according to evidence-based principles on causality. On the other hand, the study results are heterogeneous, and more objective meta-analysis shows SSDs to have a "small" effect on BMI (Forshee et al., 2008 Forshee, R. A., Anderson, P. A. and Storey, M. L. 2008. Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis. Am. J. Clin. Nutr., 87: 1662–1671. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]); therefore, a focus on fructose and SSD may then serve only to divert attention from major causes of obesity (Storey, 2008 Storey, M. 2008. Reply to M Bes-Rastrollo and MA Martinez-Gonzalez. Am. J. Clin. Nutr., 88: 1451–1452. [Google Scholar]). A number of complications and false claims arise when interpreting epidemiological and interventional studies on fructose or SSDs. The first is a notion that high-fructose corn syrup (HFCS) differs from sucrose owing to its name "high fructose," which places the focus on fructose; however, the composition and short-term metabolic effects of these sugars are similar (Stanhope and Havel, 2008 Stanhope, K. L. and Havel, P. J. 2008. Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr. Opin. Lipidol., 19: 16–24. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Second, fructose can be a surrogate marker for added sugars, for which some adverse effect is relatable to their glycemic load (Livesey and Taylor, 2008 Livesey, G. and Taylor, R. 2008. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr., 88: 1419–1437. [PubMed], [Web of Science ®] , [Google Scholar]; Livesey et al., 2008 Livesey, G. and Taylor, R. 2008. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr., 88: 1419–1437. [PubMed], [Web of Science ®] , [Google Scholar]). Third, dietary fructose may surrogate SSD consumption or an ill lifestyle, whether fructose is a problem or not (Livesey, 2009 Livesey, G. 2009. Dose-dependent responses to fructose ingestion in health research. J. Nutr., 139: 1246S–1252S. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Fourth, fructose has been proposed to underlie the adverse effects of high-glycemic-index diets; however, this fails to explain the literature on blood glucose control by diet (Livesey and Taylor, 2008 Livesey, G. and Taylor, R. 2008. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr., 88: 1419–1437. [PubMed], [Web of Science ®] , [Google Scholar]), and fructose has a low glycemic index. Fifth, short- and long-term effects of diet may differ—those of very high or excessive doses of fructose on fasting plasma triglycerides seem as such (Livesey and Taylor, 2008 Livesey, G. and Taylor, R. 2008. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr., 88: 1419–1437. [PubMed], [Web of Science ®] , [Google Scholar]). Sixth, regarding interventional and not epidemiological studies, doses of fructose studied are often very high or excessive and relevant to only 98%, except in studies of less than one year in duration. Finally, studies published to date (2009) since the meta-analysis by Forshee et al. (2008) Forshee, R. A., Anderson, P. A. and Storey, M. L. 2008. Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis. Am. J. Clin. Nutr., 87: 1662–1671. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar] are of inadequate weight to affect their findings, as expected (Storey, 2008 Storey, M. 2008. Reply to M Bes-Rastrollo and MA Martinez-Gonzalez. Am. J. Clin. Nutr., 88: 1451–1452. [Google Scholar]). The implication for SSDs and related fructose consumption in the long term, therefore, is caloric dilution of dietary nutrient density (see below) rather than obesity. Marginal micronutrient deficiency could then replace marginal adequacy (Institute of Medicine, 2003 Institute of Medicine. 2003. "Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients)". In Macronutrients and healthful diets, 769–879. Washington, DC: National Academies Press. [Google Scholar]). Unpublished or incompletely reported studies and inverse analyses. Two unpublished or incompletely published cohort studies (see Dubois et al., 2007 Dubois, L., Farmer, A., Girard, M. and Peterson, K. 2007. Regular sugar-sweetened beverage consumption between meals increases risk of overweight among preschool-aged children. J. Am. Diet Assoc., 107: 924–934. discussion 934–935[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; O'Connor et al., 2006 O'Connor, T. M., Yang, S. J. and Nicklas, T. A. 2006. Beverage intake among preschool children and its effect on weight status. Pediatrics., 118: e1010–e1018. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) are said to demonstrate no link between overweight and SSD intake—because these studies provide insufficient data to enter into meta-analyses, they contribute further to the publication bias found by Forshee et al. (2008) Forshee, R. A., Anderson, P. A. and Storey, M. L. 2008. Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis. Am. J. Clin. Nutr., 87: 1662–1671. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]. Three reported cohort studies (Blum et al., 2005 Blum, J. W., Jacobsen, D. J. and Donnelly, J. E. 2005. Beverage consumption patterns in elementary school aged children across a two-year period. J. Am. Coll. Nutr., 24: 93–98. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]; Libuda et al., 2008 Libuda, L., Alexy, U., Sichert-Hellert, W., Stehle, P., Karaolis-Danckert, N., Buyken, A. E. and Kersting, M. 2008. Pattern of beverage consumption and long-term association with body-weight status in German adolescents–results from the DONALD study. Br. J. Nutr., 99: 1370–1379. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Tam et al., 2006 Tam, C. S., Garnett, S. P., Cowell, C. T., Campbell, K., Cabrera, G. and Baur, L. A. 2006. Soft drink consumption and excess weight gain in Australian school students: results from the Nepean study. Int. J. Obes. (Lond)., 30: 1091–1093. [Crossref] , [Google Scholar]) were analyzed inversely, that is, they linked SSD intake to body weight as a determinant. These studies showed obese persons to consume more SSDs than average (not SSDs causing obesity). Such results could arise either because energy demand is higher in the obese and is being met by SSD intake or because persons succeeding to reduce body weight by a variety of means included in their strategy the replacement of SSDs with diet drinks. Such represents a response to control energy balance and cannot be interpreted as effects of fructose on obesity. Limited research. Some results are unexpected: Three studies(Dubois et al., 2007 Dubois, L., Farmer, A., Girard, M. and Peterson, K. 2007. Regular sugar-sweetened beverage consumption between meals increases risk of overweight among preschool-aged children. J. Am. Diet Assoc., 107: 924–934. discussion 934–935[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Ebbeling et al., 2006 Ebbeling, C. B., Feldman, H. A., Osganian, S. K., Chomitz, V. R., Ellenbogen, S. J. and Ludwig, D. S. 2006. Effects of decreasing sugar-sweetened beverage consumption on body weight in adolescents: a randomized, controlled pilot study. Pediatrics., 117: 673–680. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Schulze et al., 2004 Schulze, M. B., Manson, J. E., Ludwig, D. S., Colditz, G. A., Stampfer, M. J., Willett, W. C. and Hu, F. B. 2004. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA., 292: 927–934. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) have reported that SSD intake affects body weight by more than what is suggested by Forshee et al. (2008) Forshee, R. A., Anderson, P. A. and Storey, M. L. 2008. Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis. Am. J. Clin. Nutr., 87: 1662–1671. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar] and our own meta-analyses would predict. In an additional study, the replacement of sucrose with aspartame did not affect weight loss over a period of 12 months in obese persons, but weight rebound was reduced in aspartame consumers (Blackburn et al., 1997 Blackburn, G. L., Kanders, B. S., Lavin, P. T., Keller, S. D. and Whatley, J. 1997. The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight. Am. J. Clin. Nutr., 65: 409–418. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). The reasons for these unpredicted effects are unclear. The replication of such effects has not been attempted, so there is a high risk of a false claim or inadequate interpretation (Ioannidis, 2005 Ioannidis, J. P. 2005. Why most published research findings are false. PLoS Med., 2: e124[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). None of these authors could assign the cause of effects they found to fructose versus co-ingested glucose or other carbohydrate, energy, or related ill-lifestyle choices. Beyond body weight: type-2 diabetes and lifestyle. Since more fructose has appeared in the US food supply, the rate of increase of type-2 diabetes has fallen (Livesey 2008 Livesey, G. and Taylor, R. 2008. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr., 88: 1419–1437. [PubMed], [Web of Science ®] , [Google Scholar], unpublished ecological observation). Among cross-sectional data, type-2 diabetes is most prevalent among low consumers of total fructose at all ages in adults (Livesey, 2009 Livesey, G. 2009. Dose-dependent responses to fructose ingestion in health research. J. Nutr., 139: 1246S–1252S. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Furthermore, prospective association of type-2 diabetes with free fructose is found inconsistently, and when apparent it is no stronger than that for free glucose (Janket et al., 2003 Janket, S. J., Manson, J. E., Sesso, H., Buring, J. E. and Liu, S. 2003. A prospective study of sugar intake and risk of type 2 diabetes in women. Diabetes Care., 26: 1008–1015. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Meyer et al., 2000 Meyer, K. A., Kushi, L. H., Jacobs, D. R. J., Slavin, J., Sellers, T. A. and Folsom, A. R. 2000. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am. J. Clin. Nutr., 71: 921–930. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Montonen et al., 2007 Montonen, J., Järvinen, R., Knekt, P., Heliövaara, M. and Reunanen, A. 2007. Consumption of sweetened beverages and intakes of fructose and glucose predict type 2 diabetes occurrence. J. Nutr., 137: 1447–1454. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Fructose in sucrose has been associated with a lower incidence of type-2 diabetes (Janket et al., 2003 Janket, S. J., Manson, J. E., Sesso, H., Buring, J. E. and Liu, S. 2003. A prospective study of sugar intake and risk of type 2 diabetes in women. Diabetes Care., 26: 1008–1015. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Meyer et al., 2000 Meyer, K. A., Kushi, L. H., Jacobs, D. R. J., Slavin, J., Sellers, T. A. and Folsom, A. R. 2000. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am. J. Clin. Nutr., 71: 921–930. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Montonen et al., 2007 Montonen, J., Järvinen, R., Knekt, P., Heliövaara, M. and Reunanen, A. 2007. Consumption of sweetened beverages and intakes of fructose and glucose predict type 2 diabetes occurrence. J. Nutr., 137: 1447–1454. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]); statistical data have shown the meta-analytical relative risk of 0.85, with a 95% confidence interval of 0.73–0.97 (INLogic Ltd, unpublished, 2008). Frequent SSD intake and type-2 diabetes have also been associated prospectively (Schulze et al., 2004 Schulze, M. B., Manson, J. E., Ludwig, D. S., Colditz, G. A., Stampfer, M. J., Willett, W. C. and Hu, F. B. 2004. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA., 292: 927–934. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). However, caloric dilution of non-soda-related dietary energy by SSDs is approximately five times too small to explain an associated 50% to 60% lower nutrient density for magnesium and cereal fiber, and a 25% lower physical activity. Moreover, a simultaneous increase by 20% occurs in glycemic load. These and likely other lifestyle factors associate independently with type-2 diabetes and collectively would confound the interpretation 'effect caused by SSDs'. Furthermore, meta-analyses of limited data have shown that fructose at doses consumed by the majority of persons in the United States will lower HbA1c and marginally, although not significantly, improve insulin sensitivity and fasting plasma triglycerides (Livesey and Taylor, 2008 Livesey, G. and Taylor, R. 2008. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr., 88: 1419–1437. [PubMed], [Web of Science ®] , [Google Scholar]; Livesey, 2009 Livesey, G. 2009. Dose-dependent responses to fructose ingestion in health research. J. Nutr., 139: 1246S–1252S. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). With respect to type-2 diabetes, a causative role for fructose per se—or even a preventative role of moderate or possibly higher intake of pure fructose—remains to be established (Livesey and Taylor, 2008 Livesey, G. and Taylor, R. 2008. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am. J. Clin. Nutr., 88: 1419–1437. [PubMed], [Web of Science ®] , [Google Scholar]; Livesey, 2009 Livesey, G. 2009. Dose-dependent responses to fructose ingestion in health research. J. Nutr., 139: 1246S–1252S. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). The observations reported herein are consistent with a view that many claims in the scientific literature are false (Ioannidis, 2005 Ioannidis, J. P. 2005. Why most published research findings are false. PLoS Med., 2: e124[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) and that there is need for insightful meta-analyses.