
Fructose Molecule
The more we study fructose, the more it emerges as a nasty disregulator of metabolism. Is it heresy for me to place such harsh blame upon a common sugar found in fruit? Review the scientific literature and you might reach the same frightening conclusion. To clarify, I am not condemning fruit in quantities under five servings per day. Anyone attempting to lean out, though, should greatly limit fruit intake.
Warning – this post contains scientific babble about biochemical processes and how they’re (negatively) affected by fructose. Proceed with caution.
Fructose consumption has indeed increased in the US in the last hundred years. Changing from 37g/day in 1977-1978 (which is probably a little more than we consumed in 1900) to 55g/day in 1988-19941 and on to between 70 and 100g/day today2. As of 2005, Americans consumed 64kg of added sugars (any kind), which represents an increase of nearly 20% since 19703. A large part of this increase would be fructose, given that High Fructose Corn Syrup came to popularity after 1970 and that fructose represents 50% of sucrose, a common added sugar. Along with this large increase in fructose intake has come an epidemic of diabetes, obesity and other symptoms related to metabolic syndrome, and there is considerable agreement among the scientific community that fructose contributes heavily to these disorders of metabolism3.
The question has been studied extensively in animals and humans, though the evidence isn’t as certain in humans. This is likely due to the difficult nature of controlling the human diet, even in a clinical setting. The major associations with the metabolic syndrome are: hypertriglyceridemia, hypertension, visceral adiposity, low HDL cholesterol and elevated blood glucose. Three of the five of these must be present for a medical diagnosis of the disorder. In addition, fructose seems to also be related to kidney stones, gout and chronic kidney disease4. The most consistent finding in the literature is the ability of fructose to elevate triglycerides in animals and humans. De novo lipogenesis (the creation of new fat) in the liver is stimulated with fructose feeding, likely due to the fact that fructose skips several points of regulation in glycolysis, the most important being the enzyme phosphofructokinase. As a result, considerable acetyl-CoA can be made from fructose, which is a substrate for lipid synthesis5,6.
Interestingly, fructose seems to be able to upregulate its own receptors and enzymes via positive feedback7 (an interesting capability considering positive feedback is not used very widely in the body). In the short term, fructose appears to lower blood sugar levels, but in the long term there is consistent evidence that it induces insulin resistance, which leads to hyperglycemia. This is partially attributed to the accumulation of triglycerides in cells (of the liver, the muscle, etc), but also appears related to the creation of reactive oxygen species (ROS) and increase in inflammatory signals like tumor necrosis factor alpha and nuclear factor-kB5,7 in addition to other cellular stress.
Fructose has a well-documented ability to increase uric acid concentration in the blood. Aside from obvious implications with gout, uric acid level has been shown to be a predictor of hypertension in 15 out of 16 studies even independent of other conditions2,4,8. Fructose directly, however, has not been found to cause hypertension in all studies9. Though fructose appears to increase LDL, oxLDL and smLDL cholesterol levels (suggesting elevated risk for cardiovascular disease), affect on HDL seems less clear3. Elevated triglycerides and cortisol provide legitimate means of increasing intraabdominal fat deposition, but this has not been definitely answered by the literature6.
Overall, the evidence is overwhelming that increased fructose intake, especially over 50g/day, leads to increased incidences of the metabolic syndrome with only one of thirteen included studies largely in disagreement12. It is noteworthy that a fructose manufacturer funded the dissenting study.
Sources
1. Bantle, J. P. “Dietary Fructose and Metabolic Syndrome and Diabetes.” Journal of Nutrition 139.6 (2009): 1263S-268S. Web.
2. Segal, Mark S. “Is the Fructose Index More Relevant With Regards to Cardiovascular Disease than the Glycemic Index?” European Journal of Nutrition 46 (2007): 406-17. Web.
3. Hofmann, Susanna M., and Matthias H. Tschöp. “Dietary Sugars: a Fat Difference.” Journal of Clinical Investigation 119.5 (2009): 1089-092. Web.
4. Choi, M. E. “The Not-so-Sweet Side of Fructose.” Journal of the American Society of Nephrology 20.3 (2009): 457-59. Web.
5. Ferder, Leon, Marcelo D. Ferder, and Felipe Inserra. “The Role of High-Fructose Corn Syrup in Metabolic Syndrome and Hypertension.” Current Hypertension Reports 12 (2010): 105-12. Web.
6. Senesi, Silvia, Balazs Legeza, Zoltan Balazs, and Miklos Csala. “Contribution of Fructose-6-Phosphate to Glucocorticoid Activation in the Endoplasmic Reticulum: Possible Implication in the Metabolic Syndrome.” Endocrinology 151.10 (2010): 4830-839. Web
7. Lê, Kim-Anne, and Luc Tappy. “Metabolic Effects of Fructose.” Current Opinion in Clinical Nutrition and Metabolic Care 9.4 (2006): 469-75. Web.
8. Johnson, R. J., S. E. Perez-Pozo, Y. Y. Sautin, J. Manitius, L. G. Sanchez-Lozada, D. I. Feig, M. Shafiu, M. Segal, R. J. Glassock, M. Shimada, C. Roncal, and T. Nakagawa. “Hypothesis: Could Excessive Fructose Intake and Uric Acid Cause Type 2 Diabetes?”Endocrine Reviews 30.1 (2008): 96-116. Web.
9. Axelsen, Lene N., Jacob B. Lademann, and Jorgen Petersen. “Cardiac and Metabolic Changes in Long-term High Fructose-fat Fed Rats with Severe Obesity and Extensive Intramyocardial Lipid Accumulation.” American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 298 (2010): R1560-1570. Web.
10. Roncal, Carlos A., Sirirat Reungjui, Laura Gabriela Sánchez-Lozada, Wei Mu, Yuri Y. Sautin, Takahiko Nakagawa, and Richard J. Johnson. “Combination of Captopril and Allopurinol Retards Fructose-Induced Metabolic Syndrome.” American Journal of Nephrology 30.5 (2009): 399-404. Web.
11. Elliott, Sharon S., Nancy L. Keim, Judith S. Stern, Karen Teff, and Peter J. Havel. “Fructose, Weight Gain, and the Insulin Resistance Syndrome.” American Journal of Clinical Nutrition 76 (2002): 911-22. Web.
12. Livesey, Geoffrey, and Richard Taylor. “Fructose Consumption and Consequences for Glycation, Plasma Triacyglycerol, and Body Weight: Meta-analyses and Meta-regression Models of Intervention Studies.” American Journal of Clinical Nutrition 88 (2008): 1419-437. Web.
13. De Moura, Rodrigo Ferreira, Carla Ribeiro, Juliana Aparecida De Oliveira, Eliane Stevanato, and Maria Alice Rostom De Mello. “Metabolic Syndrome Signs in Wistar Rats Submitted to Different High-fructose Ingestion Protocols.” British Journal of Nutrition101.08 (2009): 1178. Web.