HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hine, R J. Search for Related Content PubMed PubMed Citation Articles by Hine, R J. Agricola Articles by Hine, R J.

Time to get specific about dietary carbohydrates, affected populations, and diseases

Winthrop P Rockefeller Cancer Institute
University of Arkansas for Medical Sciences
4301 W Markham Street, slot 753
Little Rock, AR 72205
E-mail: hinerjean{at}uams.edu

Dear Sir:

Johnson et al (1) suggested in review published in the October issue of the Journal that excess dietary fructose has a role in the epidemic of obesity, metabolic syndrome, diabetes, and renal and cardiovascular diseases. They point to sugar's unique ability to elevate uric acid concentrations as one mechanism explaining the link between fructose and cardiorenal disease. The review and accompanying editorial comment by Bray (2) underscore the need for data about the metabolic, molecular, and physiologic effects of dietary sugars, especially fructose. Scientists conducting nutrition research have an opportunity to expand concepts about the roles of dietary carbohydrates in human health.

Exploring the complex dose-response effects of acute and long-term fructose exposure in human subjects or animal models should be a priority for several reasons. Fructose is not only present in foods, but also in beverages and certain medications. It is also produced endogenously when hyperglycemia triggers activation of the polyol (aldose reductase) pathway (3). Conversion of glucose to fructose in the polyol pathway contributes to diabetic neuropathy, possibly through depletion of glutathione and increased activation of c-Jun N-terminal kinase. Kawasaki et al (4, 5) reported elevated serum fructose concentrations in patients with type 2 diabetes compared with controls and showed an association between postprandial plasma fructose and retinopathy.

Western blot analyses have shown that intestinal protein concentrations of GLUT-5, the fructose transport protein, are increased 4-fold in type 2 diabetes, which suggests better uptake of fructose from the gut (6). In contrast with Bray's statement, "most cells have only low amounts of the GLUT-5 transporter, which transports fructose into cells," the GLUT-5 hexose transport protein is expressed in many tissues and cells, including skeletal muscle, testes, adipocytes, erythrocytes, and macrophages. GLUT-5 is overexpressed in several malignancies; it was detected in 30 of 33 of the invasive breast ductal carcinomas (6). Pancreatic cancer risk is increased in those with long-standing diabetes, and it is becoming clearer that dysregulated carbohydrate metabolism may be an etiological factor (7). One case control study showed that women who were both overweight and sedentary and had a high fructose intake had a relative risk of 3.17 (8). Several observational studies have examined the relation between carbohydrate intake and pancreatic cancer, but results have been inconsistent (9). In view of the prominence of carbohydrates in human diets, novel directions in carbohydrate research are timely.

ACKNOWLEDGMENTS

No conflicts of interest were reported.

REFERENCES

1. Johnson RJ, Segal MS, Sautin Y, et al. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr 2007;86(4):899–906.[Abstract/Free Full Text]
2. Bray GA. How bad is fructose? Am J Clin Nutr 2007;86(4):895–6.[Free Full Text]
3. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414(6865):813–20.[Medline]
4. Kawasaki T, Akanuma H, Yamanouchi T. Increased fructose concentrations in blood and urine in patients with diabetes. Diabetes Care 2002;25(2):353–7.[Abstract/Free Full Text]
5. Kawasaki T, Ogata N, Akanuma H, et al. Postprandial plasma fructose level is associated with retinopathy in patients with type 2 diabetes. Metabolism 2004;53(5):583–8.[Medline]
6. Dyer J, Wood IS, Palejwala A, Ellis A, Shirazi-Beechey SP. Expression of monosaccharide transporters in intestine of diabetic humans. Am J Physiol Gastrointest Liver Physiol 2002;282(2):G241–8.[Abstract/Free Full Text]
7. Hine RJ, Srivastava S, Milner JA, Ross SA. Nutritional links to plausible mechanisms underlying pancreatic cancer: a conference report. Pancreas 2003;27(4):356–66.[Medline]
8. Michaud DS, Liu S, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. J Natl Cancer Inst 2002;94(17):1293–300.[Abstract/Free Full Text]
9. Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 2007;132(6):2208–25.[Medline]

This article has been cited by other articles:

				J. S. White Misconceptions about High-Fructose Corn Syrup: Is It Uniquely Responsible for Obesity, Reactive Dicarbonyl Compounds, and Advanced Glycation Endproducts? J. Nutr., June 1, 2009; 139(6): 1219S - 1227S. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hine, R J. Search for Related Content PubMed PubMed Citation Articles by Hine, R J. Agricola Articles by Hine, R J.