FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4256247079> ?p ?o ?g. }

• W4256247079 endingPage "993" @default.
• W4256247079 startingPage "990" @default.
• W4256247079 abstract "Livesey disputes several points in my original Journal of the American Dietetic Association article (1Lustig R.H. Fructose: Metabolic, hedonic, and societal parallels with ethanol.J Am Diet Assoc. 2010; 110: 1307-1321Google Scholar), in which I elaborate the parallels between fructose and ethanol. Livesey advances his argument that fructose when ingested alone is a safe, nontoxic foodstuff based on the following points: 1) measurement of de novo lipogenesis (DNL) in response to fructose ingestion alone is low; 2) the potential value of fructose for glucose exchange as a sweetener for type 2 diabetes because it does not raise blood glucose (and, therefore, hemoglobin A1c); 3) the assertion that studies of fructose do not show decompensation of insulin sensitivity until oral doses reach 150 g; 4) according to the proposed model, insulin resistance occurs in response to cytokine production from adipocytes, not from fructose per se; and 5) the Journal article is not a systematic review because it does not discuss fructose for glucose exchange studies. I will respond to each point in turn. 1Livesey cites data that DNL in response to fructose is not elevated. As stated both in the Journal article and in the response to Sievenpiper and colleagues (2Sievenpiper J.L. de Souza R.J. Kendall C.W.C. Jenkins D.J.A. Is fructose a story of mice but not men?.J Am Diet Assoc. 2011; 111: 219-220Google Scholar), measurement and interpretation of DNL must appreciate the context. Factors that increase the DNL associated with fructose include: a) nonfasting conditions (3Schwarz J.M. Linfoot P. Dare D. Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets.Am J Clin Nutr. 2003; 77: 43-50Google Scholar); b) hypercaloric feeding (4Stanhope K.L. Schwarz J.M. Keim N.L. Griffen S.C. Bremer A.A. Graham J.L. Hatcher B. Cox C.L. Dyachenko A. Zhang W. McGahan J.P. Seibert A. Krauss R.M. Chiu S. Schaefer E.J. Ai M. Otokozawa S. Nakajima K. Nakano T. Beysen C. Hellerstein M.K. Berglund L. Havel P.J. Consuming fructose-, not glucose-sweetened beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans.J Clin Invest. 2009; 119: 1322-1334Google Scholar); c) degree of obesity and insulin resistance (3Schwarz J.M. Linfoot P. Dare D. Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets.Am J Clin Nutr. 2003; 77: 43-50Google Scholar); and, most importantly, d) the presence of concomitant ingested glucose (5Hudgins L.C. Parker T.S. Levine D.M. Hellerstein M.K. A dual sugar challenge test for lipogenic sensitivity to dietary fructose.J Clin Endocrinol Metab. 2011; 96: 861-868Google Scholar). Livesey, as did Sievenpiper, quotes Parks and colleagues from 1999 (6Parks E.J. Krauss R.M. Christiansen M.P. Neese R.A. Hellerstein M.K. Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance.J Clin Invest. 1999; 104: 1087-1096Google Scholar) showing that DNL in response to fructose alone in the fasted, glycogen-depleted state is negligible at less than 5% (importantly, Hellerstein was the senior author of this paper). More recently, Hudgins and colleagues (5Hudgins L.C. Parker T.S. Levine D.M. Hellerstein M.K. A dual sugar challenge test for lipogenic sensitivity to dietary fructose.J Clin Endocrinol Metab. 2011; 96: 861-868Google Scholar) (Hellerstein was senior author here as well) demonstrate that fructose and glucose are synergistic, with DNL tripling with fructose upon concomitant glucose ingestion; and the effect knows no asymptote, as doubling the fructose and glucose ingested quintuples the DNL over fructose alone. This makes sense because in the fasted, glycogen-depleted state, fructose alone can be diverted at the fructose-6-phosphate step back to glycogenesis to replete glycogen; but in the glycogen-replete, hypercaloric, or sucrose-fed state, the glucose will drive hepatic glycogenesis, leaving fructose no choice but to enter the hepatic lipogenic pathway. It should be noted that there is nowhere in nature where fructose occurs in isolation. Thus, performing DNL studies with fructose for glucose exchange is artifactual because fructose is not a foodstuff; sugar (sucrose) and high-fructose corn syrup are. It's not fructose for glucose; it's fructose and glucose, everywhere, every time. With rare exceptions (such as agave nectar which is 75% fructose), it's a 50-50 split. Furthermore, it has been shown that fructose ingested alone is poorly absorbed from the gastrointestinal tract (7Rumessen J.J. Gudmand-Hoyer E. Absorption capacity of fructose in healthy adults Comparison with sucrose and its constituent monosaccharides.Gut. 1986; 27: 1161-1168Google Scholar), while concomitant glucose ingestion increases absorption to virtually 100%. Therefore, measurement of DNL with fructose alone is quadruply artifactual, and Livesey's point is moot.2Livesey points to his own meta-analysis demonstrating that crystalline fructose consumption alone does not increase blood glucose or hemoglobin A1c in type 2 diabetes (8Livesey G. Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol and body weight: meta-analyses and meta-regression models of intervention studies.Am J Clin Nutr. 2008; 88: 1419-1437Google Scholar). Indeed, fructose ingestion alone generates an extremely minimal glucose response. Perhaps one reason is because crystalline fructose is incompletely absorbed and, thus, its effects on glucose and HbA1c may be minimal. If so, then the gastrointestinal symptoms of the residual fructose in the intestine are maximal, generating pain, bloating, and diarrhea (9Fernández-Bañares F. Esteve M. Viver J.M. Fructose-sorbitol malabsorption.Curr Gastroenterol Rep. 2009; 11: 368-374Google Scholar). I should point out that the analogy to ethanol works here as well, as ethanol also does not raise blood sugar; indeed, it can cause hypoglycemia. However, Japanese researchers have demonstrated that advanced fructosylated endproducts are easily detectable, especially in people with diabetes (10Takeuchi M. Iwaki M. Takino J. Shirai H. Kawakami M. Bucala R. Yamagishi S. Immunological detection of fructose-derived advanced glycation end-products.Lab Invest. 2010; 90: 1117-1127Google Scholar). Indeed, fructose increases uric acid and reactive oxygen species in humans (11Perez-Pozo S.E. Schold J. Nakagawa T. Sánchez-Lozada L.G. Johnson R.J. Lillo J.L. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: Role of uric acid in the hypertensive response.Int J Obes. 2010; 34: 454-461Google Scholar, 12Ouyang X. Cirillo P. Sautin Y. McCall S. Bruchette J.L. Diehl A.M. Johnson R.J. Abdelmalek M.F. Fructose consumption as a risk factor for non-alcoholic fatty liver disease.J Hepatol. 2008; 48: 993-999Google Scholar). Furthermore, in an in vitro system incubating hemoglobin A with fructose, molecular modeling reveals Lys7alpha, Lys127alpha, and Lys66beta as targets of fructation; if this occurred in vivo, these adducts might not be picked up in a traditional HbA1c assay using high-performance liquid chromatography (13Bose T. Chakraborti A.S. Fructose-induced structural and functional modifications of hemoglobin: Implication for oxidative stress in diabetes mellitus.Biochim Biophys Acta. 2008; 1780: 800-808Google Scholar). It is possible that serum glucose and HbA1c are the wrong endpoints. Thus, Livesey's point about fructose improving diabetes parameters is highly debatable.3Livesey quotes his own article that decompensation in insulin sensitivity occurs only after massive fructose consumption (14Livesey G. Fructose ingestion: Dose-dependent responses in health research.J Nutr. 2009; 139: 1246S-1252SGoogle Scholar). In the Journal article (1Lustig R.H. Fructose: Metabolic, hedonic, and societal parallels with ethanol.J Am Diet Assoc. 2010; 110: 1307-1321Google Scholar), I show that fructose equates metabolically with ethanol. Ethanol consumed alone (eg, wine or spirits) in moderation can also improve insulin sensitivity (15Di Castelnuovo A. Costanzo S. di Giuseppe R. de Gaetano G. Iacoviello L. Alcohol consumption and cardiovascular risk: Mechanisms of action and epidemiologic perspectives.Future Cardiol. 2009; 5: 467-477Google Scholar, 16Facchini F. Chen Y.D. Reaven G.M. Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity.Diabetes Care. 1994; 17: 115-199Google Scholar), but when overconsumed with glucose (eg, beer, shochu), it leads to features of the metabolic syndrome (17Athyros V.G. Liberopoulos E.N. Mikhailidis D.P. Papageorgiou A.A. Ganotakis E.S. Tziomalos K. Kakafika A.I. Karagiannis A. Lambropoulos S. Elisaf M. Association of drinking pattern and alcohol beverage type with the prevalence of metabolic syndrome, diabetes, coronary heart disease, stroke, and peripheral arterial disease in a Mediterranean cohort.Angiology. 2007; 58: 689-697Google Scholar, 18Sakurai Y. Umeda T. Shinchi K. Honjo S. Wakabayashi K. Todoroki I. Nishikawa H. Ogawa S. Katsurada M. Relation of total and beverage-specific alcohol intake to body mass index and waist-to-hip ratio: A study of self-defense officials in Japan.Eur J Epidemiol. 1997; 13: 893-898Google Scholar). Almost assuredly this is because of the glucose monopolizing the hepatic glycogenic pathway, leaving the ethanol to drive the DNL pathway. Similarly, it is possible that fructose alone could improve insulin sensitivity; however, as already stated, fructose is always consumed with glucose. And as stated previously, fructose consumed alone is incompletely absorbed. Therefore, determining a rational amount of fructose consumption must utilize sucrose or high-fructose corn syrup as a starting point. The American Heart Association has set a recommendation of 9 tsp of added sugar for the average American man (22.5 g fructose) and 6 tsp of added sugar for the average American woman (15 g fructose) (19Johnson R.K. Appel L.J. Brands M. Howard B.V. Lefevre M. Lustig R.H. Sacks F. Steffen L. Wylie-Rosett J. American Heart Association Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism and the Council on Epidemiology and PreventionDietary sugars intake and cardiovascular health A scientific statement from the American Heart Association.Circulation. 2009; 120: 1011-1020Google Scholar). Therefore, Livesey's point regarding dosage of fructose alone is immaterial.4Livesey suggests with his model that insulin resistance can only be generated from adipose tissue expansion with resultant cytokine development. However, Fabbrini and colleagues (20Fabbrini E. Magkos F. Mohammed B.S. Pietka T. Abumrad N.A. Patterson B.W. Okunade A. Klein S. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity.Proc Natl Acad Sci. 2009; 106: 15430-15435Google Scholar) demonstrated that hepatic lipid deposition (which occurs in response to fructose [21Lim J.S. Mietus-Snyder M. Valente A. Schwarz J.M. Lustig R.H. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome.Nat Rev Gastroenterol Hepatol. 2010; 7: 251-264Google Scholar]) is a primary etiology of peripheral insulin resistance, and Kung and Kim have shown that nonalcoholic fatty liver disease is a primary determinant of the development of type 2 diabetes, even after controlling for body mass index (22Sung K.C. Kim S.H. Interrelationship between fatty liver and insulin resistance in the development of type 2 diabetes.J Clin Endocrinol Metab. 2011; 96: 1093-1097Google Scholar). Furthermore, insulin hypersecretion can downregulate peripheral insulin receptors (23Lustig R.H. Which comes first? The obesity or the insulin? The behavior or the biochemistry?.J Pediatr. 2008; 152: 601-602Google Scholar, 24Shanik M.H. Xu Y. Skrha J. Dankner R. Zick Y. Roth J. Insulin resistance and hyperinsulinemia: Is hyperinsulinemia the cart or the horse?.Diabetes Care. 2008; 31: S262-S268Google Scholar), generating insulin resistance independent of fat deposition. Thus, fructose-induced hepatic insulin resistance, with its reflex hyperinsulinemia, can promote insulin resistance. Finally, we know that nonobese people harbor significant insulin resistance if they exhibit fatty liver (25Sung K.C. Ryan M.C. Kim B.S. Cho Y.K. Kim B.I. Reaven G.M. Relationships between estimates of adiposity, insulin resistance, and nonalcoholic fatty liver disease in a large group of nondiabetic Korean adults.Diabetes Care. 2007; 30: 2113-2118Google Scholar), while 20% of obese people have normal insulin sensitivity (26Chan J.M. Rimm E.B. Colditz G.A. Stampfer M.J. Willett W.C. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men.Diabetes Care. 1994; 17: 961-969Google Scholar), showing that peripheral adiposity and insulin resistance can be dissociated by the presence of liver fat, which is easily generated by fructose. Thus, I refute Livesey's model as fundamentally flawed.5Livesey challenges the Journal article (1Lustig R.H. Fructose: Metabolic, hedonic, and societal parallels with ethanol.J Am Diet Assoc. 2010; 110: 1307-1321Google Scholar) because it does not systematically evaluate fructose for glucose exchange studies. It was not supposed to. He points to Dolan and colleagues (27Dolan L.C. Potter S.M. Burdock G.A. Evidence-based review of the effect of normal dietary consumption of fructose on development of hyperlipidemia and obesity in healthy, normal-weight individuals.Crit Rev Food Sci Nutr. 2010; 50: 53-84Google Scholar), Rizkalla (28Rizkalla S.W. Health implications of fructose consumption: a review of recent data.Nutr Metab. 2010; 7: 82Google Scholar), and others which perform that function; but each of these qualify their conclusions as showing that fructose does not cause harm after “normal” levels of consumption, quoting Marriott and colleagues (29Marriott B.P. Cole N. Lee E. National estimates of dietary fructose intake increased from 1977 to 2004 in the United States.J Nutr. 2009; 139: 1228S-1235SGoogle Scholar). However, as I've already stated, such comparisons are irrelevant, because: a) there is no fructose for glucose in nature (there is only fructose and glucose); and b) “normal” consumption (less than 50 g/day) has been exceeded in every retrospective assessment, including Marriott and colleagues' most recent review (30Marriott B.P. Olsho L. Hadden L. Connor P. Intake of added sugars and selected nutrients in the United States, National Health and Nutrition Examination Survey, 2003-2006.Crit Rev Food Sci Nutr. 2010; 50: 228-258Google Scholar). Rather, the point (and title) of the Journal article was to systematically evaluate the similarities between fructose and ethanol—a point which seems to be ignored by Livesey. More on Mice and Men: Fructose Could put Brakes on a Vicious Cycle Leading to Obesity in HumansJournal of the American Dietetic AssociationVol. 111Issue 7PreviewThe role played by dietary fructose in the ‘epidemic’ of obesity has recently been debated in the Journal of the American Dietetic Association (1,2) following the earlier review by Lustig (3) in which fructose is argued to have a prominent role in the causation and perpetuation of obesity. These warrant comment because the arguments do not represent the literature in humans on this topic and literature is cited inaccurately, particularly in regard to my own work. Full-Text PDF" @default.
• W4256247079 created "2022-05-12" @default.
• W4256247079 creator A5003686041 @default.
• W4256247079 date "2011-07-01" @default.
• W4256247079 modified "2023-10-03" @default.
• W4256247079 title "Author's Response" @default.
• W4256247079 cites W1975855856 @default.
• W4256247079 cites W1976865835 @default.
• W4256247079 cites W1981412729 @default.
• W4256247079 cites W1994654737 @default.
• W4256247079 cites W2007427142 @default.
• W4256247079 cites W2017948134 @default.
• W4256247079 cites W2025578932 @default.
• W4256247079 cites W2026692048 @default.
• W4256247079 cites W2029046331 @default.
• W4256247079 cites W2034700421 @default.
• W4256247079 cites W2049558671 @default.
• W4256247079 cites W2066992761 @default.
• W4256247079 cites W2071934181 @default.
• W4256247079 cites W2077963393 @default.
• W4256247079 cites W2080304351 @default.
• W4256247079 cites W2083474315 @default.
• W4256247079 cites W2096695567 @default.
• W4256247079 cites W2109175091 @default.
• W4256247079 cites W2115600950 @default.
• W4256247079 cites W2121562893 @default.
• W4256247079 cites W2130234883 @default.
• W4256247079 cites W2134275826 @default.
• W4256247079 cites W2141823673 @default.
• W4256247079 cites W2142795326 @default.
• W4256247079 cites W2146966453 @default.
• W4256247079 cites W2162696374 @default.
• W4256247079 cites W2170347119 @default.
• W4256247079 cites W2170649441 @default.
• W4256247079 cites W317365657 @default.
• W4256247079 doi "https://doi.org/10.1016/j.jada.2011.05.019" @default.
• W4256247079 hasPublicationYear "2011" @default.
• W4256247079 type Work @default.
• W4256247079 citedByCount "7" @default.
• W4256247079 countsByYear W42562470792012 @default.
• W4256247079 countsByYear W42562470792013 @default.
• W4256247079 countsByYear W42562470792014 @default.
• W4256247079 crossrefType "journal-article" @default.
• W4256247079 hasAuthorship W4256247079A5003686041 @default.
• W4256247079 hasBestOaLocation W42562470791 @default.
• W4256247079 hasConcept C15744967 @default.
• W4256247079 hasConceptScore W4256247079C15744967 @default.
• W4256247079 hasIssue "7" @default.
• W4256247079 hasLocation W42562470791 @default.
• W4256247079 hasOpenAccess W4256247079 @default.
• W4256247079 hasPrimaryLocation W42562470791 @default.
• W4256247079 hasRelatedWork W2053487507 @default.
• W4256247079 hasRelatedWork W2067108088 @default.
• W4256247079 hasRelatedWork W2077865380 @default.
• W4256247079 hasRelatedWork W2083375246 @default.
• W4256247079 hasRelatedWork W2085372204 @default.
• W4256247079 hasRelatedWork W2134894512 @default.
• W4256247079 hasRelatedWork W2748952813 @default.
• W4256247079 hasRelatedWork W2765597752 @default.
• W4256247079 hasRelatedWork W2899084033 @default.
• W4256247079 hasRelatedWork W2931662336 @default.
• W4256247079 hasVolume "111" @default.
• W4256247079 isParatext "false" @default.
• W4256247079 isRetracted "false" @default.
• W4256247079 workType "article" @default.