RECOMMENDED ARTICLES ON DIETARY ISSUES
Sugar Buzz Lustig & fructose and NAFLD articles
Home
Sugar Buzz Lustig & fructose and NAFLD articles
Low Carb management of type-2 diabetes-review
Fructose pathology
Water fast of 382 days a therapeutic success
Insulin Reistance and Fatty Liver, at the heart of the storm--Fung
Excess sugar and fatty liver experiment, heart of storm

Three articles, the most important is last, that of Prof Robert Lustig MD on how fructose damages the liver in the same ways as ethanol, fat accumulation in the liver and reactive products of metabolism

Thus is a 2013 summation article on what has been proven about the effects of fructose upon the body, with special emphasis as to the harm it does compared to its sister monosaccharide glucose.

Background information:  Insulin is the hormone which regulates glucose levels in the blood.  To lower elevated glucose in the blood insulin directs cells, most significantly muscle and fat cells to absorb from the blood glucose and to metabolize glucose, thus thereby to shut down fat metabolism and thus to store fat.  1) Oxidative damage to endothelial cells is the initiating event leading to atherosclerosis, cardiovascular disease and the resultant heart attacks, strokes, and kidney damage. {This is more pharma spin used to promote the sales of statins drugs through their lipid hypothesis—see link for rebuttal. 2) Oxidative damage and glycation are the greatest causes for aging process.  Glycation is the undirected (non-enzymatic) attaching of a simple sugar to a protein which interferes with the function of that protein. 3) Glucose and fructose cause the production of peroxides which also cause oxidative damage, fructose being 7.5 times a greater cause.  This is made worse because it accumulates in the liver where it is metabolized.  The net-negative effect upon the liver is at least 15 fold greater through glycation than glucose. 4) Glycation and oxidation damages liver including causing hepatic insulin resistance.  5)  Insulin resistance cause excess fat storage in the liver, which further compromises liver functions.  6)  Among the compromised functions is that of a slower clearance of glucose from the blood by the liver, which then results in increased serum insulin.  7) When cells have sufficient glucose—as on a high carb diet—they resist the uptake of more glucose, thus causing the pancreas to release even more insulin.  8)  This process is at the core for the diabetes and obesity epidemics:  a high carb diet with too much fructose.  A high carb diet, as those on a traditional Chinese and Japanese diet which is low in fructose is without those pathologies.   

One important point is the putative association of high LDL with cardiovascular disease is putting the cart before the horse.  The horse is fructose and its casual role in NAFLD, insulin resistance, damage to endothelial cells that line the arteries (and thus promotes atherosclerosis), etc.  Bad pharma ones to treat a sign high LDL rather than the cause fructose and the liver damage it causes which through off the regulation of weight, blood glucose, etc.  Remember that pharma profits from chronic conditions.  They should have measured the increase in fat in the liver with a sonogram and blood insulin for Insulin resistance.  But pharma has them looking under the wrong tree, probably through funding of trial and thereby setting up the primary endpoints (protocols).  For more on the cholesterol myth click on link & watch the many documentaries and lectures on YouTube.  It is mind boggling how the large chorus of critics is ignored by the medical education system and thus doctors and the corporate media.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

First article:  Though it doesn’t mention damage by glycation, the attachment of fructose to proteins, it is described: “owing to the molecular instability of its five-membered furanose ring, fructose promotes protein fructosylation and formation of reactive oxygen species (ROS), which require quenching by hepatic antioxidants.´ This has to be the first hit, since it occurs when fructose is transported to the liver, the process of fat accumulation is gradual over years, and thus doesn’t become pathogenic for years, while from the start protein in the liver are compromised by fructose.

 

http://www.nature.com/nrgastro/journal/v7/n5/abs/nrgastro.2010.41.html

Nature Reviews Gastroenterology and Hepatology 7, 251-264 (May 2010) 

 The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome

Jung Sub Lim, Michele Mietus-Snyder, Annie Valente, Jean-Marc Schwarz & Robert H. Lustig  About the authors

topof page

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide, and is commonly associated with the metabolic syndrome. Secular trends in the prevalence of these diseases may be associated with the increased fructose consumption observed in the Western diet. NAFLD is characterized by two steps of liver injury: intrahepatic lipid accumulation (hepatic steatosis), and inflammatory progression to nonalcoholic steatohepatitis (NASH) (the 'two-hit' theory). In the first 'hit', hepatic metabolism of fructose promotes de novolipogenesis and intrahepatic lipid, inhibition of mitochondrial β-oxidation of long-chain fatty acids, triglyceride formation and steatosis, hepatic and skeletal muscle insulin resistance, and hyperglycemia. In the second 'hit', owing to the molecular instability of its five-membered furanose ring, fructose promotes protein fructosylation and formation of reactive oxygen species (ROS), which require quenching by hepatic antioxidants. Many patients with NASH also have micronutrient deficiencies and do not have enough antioxidant capacity to prevent synthesis of ROS, resulting in necro-inflammation. We postulate that excessive dietary fructose consumption may underlie the development of NAFLD and the metabolic syndrome. Furthermore, we postulate that NAFLD and alcoholic fatty liver disease share the same pathogenesis.

 

The often cited article comparing excess glucose consumption to that of excess fructose consumption in a group of paid volunteers.  Only fructose damaged promoted insulin resistance.  This is consistent with the observation that a high glucose traditional diet does not cause insulin resistance and it comorbidities 

One important point is the putative association of high LDL with cardiovascular disease is putting the cart before the horse.  The horse is fructose and its casual role in NAFLD, insulin resistance, damage to endothelial cells that line the arteries (and thus promotes atherosclerosis), etc.  Bad pharma ones to treat a sign high LDL rather than the cause fructose and the liver damage it causes which through off the regulation of weight, blood glucose, etc.  Remember that pharma profits from chronic conditions.  They should have measured the increase in fat in the liver with a sonogram and blood insulin for Insulin resistance.  But pharma has them looking under the wrong tree, probably through funding of trial and thereby setting up the primary endpoints (protocols). 

https://www.jci.org/articles/view/37385#sd    complete (only abstract copied here)

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans

Abstract:

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^

^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Criticism of Dr. Lustig on the cholesterol myth:  Dr. Lustig proposes the lipid hypothesis as to the start of the atherogenic process leading to cardiovascular disease (CVD).  This is another case of pharma treating signs of a condition, rather than its cause.  This is the power of an industry to frame a topic (in this case CVD) and through KOLs (key opinion leaders) to get their junk science accepted as medical science.  If you are interested in the cause, then I click on Cholesterol Myth.  There is a chorus of critics, but pharma’s KOLs won’t debate the issue, or even write of it in the medical textbooks.  Fortunately their control has limits and journals will publish quality articles present the real major cause of CVD and a few documentaries and lectures. Possible he has his march points, go after cholesterol and UCTV et others will black-list you and USF will cut off research funding.  Or possible he doesn’t want to raise an issue which will distract from his main theses, that fructose is poison. 

.

SUMMARY:  Fructose unhealthy consequences:  1) Causes metabolic syndrome (high blood pressure, atherosclerosis, and insulin resistance/type ii diabetes).  At 7 times the rate of glucose, fructose causes glycation of proteins through its keto group.  This process of glycation also causes oxidative damage and both promote cellular dysfunction, atherogenesis through oxidative damage to endothelial cells that line the artery walls, and affects the brain reward system in a way that promotes weight gain.  A second effect is upon the metabolic system for which fructose’s metabolism is quite different from that of glucose.  Among the results of this difference is hepatic insulin resistance, and elevated blood sugar level.  Fructose in the body is metabolized similar to ethanol. Glucose’s contribution to atherogenesis is a small fraction compared to fructose “Only 2% of ingested glucose will find its way into VLDL; thus, glucose contributes extremely slowly to cardiovascular disease and other aspects of metabolic syndrome.” 

doi: 10.3945/​an.112.002998Adv Nutr March 2013 Advanced Nutrition, an international review journal, vol. 4: 226-235, 2013   http://advances.nutrition.org/content/4/2/226.full then click on “full”.  10 pages Condensed by JK

 

Fructose: It’s “Alcohol Without the Buzz”

 

This paper compares the metabolic actions of fructose with those of glucose and ethanol to make the point that fructose is “alcohol without the buzz.”

http://advances.nutrition.org/content/4/2/226.full 2013  

Abstract

What do the Atkins Diet and the traditional Japanese diet have in common? The Atkins Diet is low in carbohydrate and usually high in fat; the Japanese diet is high in carbohydrate and usually low in fat. Yet both work to promote weight loss. One commonality of both diets is that they both eliminate the monosaccharide fructose. Glucose is the molecule that when polymerized forms starch, which has a high glycemic index, generates an insulin response, and is not particularly sweet. Fructose is found in fruit, does not generate an insulin response, and is very sweet. Fructose consumption has increased worldwide, paralleling the obesity and chronic metabolic disease pandemic.  However, fructose is unlike glucose. In the hypercaloric glycogen-replete state, intermediary metabolites from fructose metabolism overwhelm hepatic mitochondrial capacity, which promotes de novo lipogenesis and leads to hepatic insulin resistance, which drives chronic metabolic disease. Fructose also promotes reactive oxygen species formation, which leads to cellular dysfunction and aging, and promotes changes in the brain’s reward system, which drives excessive consumption.  Thus, fructose can exert detrimental health effects beyond its calories and in ways that mimic those of ethanol, its metabolic cousin. Indeed, the only distinction is that because fructose is not metabolized in the central nervous system, it does not exert the acute neuronal depression experienced by those imbibing ethanol. These metabolic and hedonic analogies argue that fructose should be thought of as “alcohol without the buzz.” 

 

Introduction

We are in the midst of a global pandemic of chronic metabolic disease, 30 y in the making. The UN Secretary General in 2011 declared that metabolic syndrome (type 2 diabetes, hypertension, dyslipidemia, heart disease) and other noncommunicable diseases (e.g., cancer, dementia) are now a greater threat to both the developed and developing worlds than is acute infectious disease, including HIV (1). Most people blame obesity as the driver of these other diseases; however, 20% of obese subjects are metabolically normal, whereas as many as 40% of normal-weight people manifest specific components of metabolic syndrome (24). Obesity is not the cause of metabolic syndrome; rather, it is a marker for the metabolic dysfunction that is occurring worldwide. Furthermore, there are now >30% more obese people on the planet than those who are malnourished. Two decades ago, it was the opposite. Is it really possible, even in the most impoverished countries, that so many people became gluttons and sloths in such a short period of time? The ever-onward progression of these diseases in countries that also witness severe malnutrition is more reminiscent of an exposure than it is an alteration in behavior.

Most people blame obesity as the driver of these other diseases; however, 20% of obese subjects are metabolically normal, whereas as many as 40% of normal-weight people manifest specific components of metabolic syndrome (24)   Currently, per capita consumption of fructose or fructose-containing disaccharides is at ∼130 lb/y (almost 60 kg/y) or 6.5 oz/d for the average American. Although America is the greatest sugar consumer, other countries are not far behind (6).  Indeed, patients with hereditary fructose intolerance, who are missing the enzyme fructose-1-phosphate aldolase B, and cannot consume fructose lest they become hypoglycemic, do not only have fewer dental caries (8), but they are quite healthy provided they continue to restrict their fructose exposure (9, 10).  Second, fructose exerts 3 different negative impacts on human metabolism, each of which is exclusive of its calories. Most people compare fructose with its isomer glucose, which is so essential for life that your liver will produce it when it is in short supply via the process of gluconeogenesis. [Not dietary essential, for Eskimos live without plants, and thus carbohydrates, yet they are healthy.]  Although fructose is an energy source, the actions of fructose on the body more closely resemble those of ethanol (grain alcohol), another nonessential energy source.

Although most people consider fructose, and sugar in general, as “empty calories,” there is nothing empty about these calories. First, there is not 1 human biochemical reaction that requires dietary fructose. The only place in the body that fructose is of physiologic import is in semen, and the fructose is manufactured de novo from glucose using the aldose reductase/sorbitol pathway (7).

Hepatic Insulin resistance and metabolic syndrome:  One reason for this puzzle is trying to explain the phenomenon of “selective hepatic insulin resistance” (13). Insulin normally exerts its effects on hepatic energy metabolism via 2 metabolic pathways.  Insulin also activates the lipogenic pathway by stimulating sterol regulatory element binding protein 1c (SREBP-1c), which activates the enzymes of de novo lipogenesis (DNL) to turn excess mitochondrial energy substrate into fatty acids, which are then linked to apolipoprotein B100 and packaged into VLDL for hepatic export.  Rather, metabolic syndrome results from “selective” hepatic insulin resistance in which FoxO1 is not phosphorylated yet SREBP-1c is still activated to promote triglyceride synthesis and dyslipidemia. If there is only 1 insulin receptor, how can it activate 1 pathway and not the other (17)? To parse this dichotomy, the hepatic metabolism of glucose, ethanol, and fructose are considered in turn. 

Hepatic glucose metabolism:  This leads to the conversion of the majority of glucose molecules as hepatic glycogen for storage. The small amount that undergoes glycolysis reaches the mitochondria as pyruvate and is quickly esterified into acetyl-CoA.  This allows any excess acetyl-CoA that cannot be β-oxidized for energy and exits the mitochondria to be rebuilt into FFAs, which then are packaged into VLDL for hepatic export and storage in adipocytes. This VLDL can promote atherogenesis and/or obesity, but only ∼2% of ingested glucose will find its way into VLDL; thus, glucose contributes extremely slowly to cardiovascular disease and other aspects of metabolic syndrome. 

 Hepatic Fructose metabolism   Only the liver possesses the Glut5 transporter (30), and the liver has a very high fructose extraction rate (31); thus, virtually an entire ingested fructose load finds its way to the liver.  In contrast to the majority of hepatic glucose being converted to glycogen in the liver under the influence of insulin, fructose does not get converted to glycogen directly [although in case of glycogen depletion due to starvation or exercise, it can be converted to fructose-6-phosphate, which is isomerized to glucose-6-phosphate, which can rebuild glycogen (32)]. Rather, fructose is phosphorylated independently of insulin to fructose-1-phosphate by the enzyme fructokinase (Fig. 3), which undergoes glycolysis, and is metabolized to pyruvate, with the resultant large volume of acetyl-CoA entering the mitochondrial tricarboxylic acid cycle,  which activates carbohydrate response element binding protein (35), stimulating the activity of DNL [causing lipogenesis].  The attachment of hepatic triglyceride to apolipoprotein B by MTP completes its conversion to VLDL, which is exported out of the liver to contribute to fructose-induced hypertriglyceridemia (39, 4143), along with the production of “small dense” LDL (44), which is particularly atherogenic because it can be oxidized rapidly and is small enough to get under the surface of vascular endothelial cells to start the foam cell process (39, 4547). [Disagree: the evidence supports active transport where LDL functions as a source for triglycerides and cholesterol for a process of repair to damage tunica media due to inflammation in that layer of the artery caused by the presence of pathogens.  The second function of LDL is that of an antibody which absorbs toxins and reactive products caused by the pathogens.  There is amply journal articles supporting this process, see Prof. Uffe Ravnskov, Ignore the Awkward pgs. 133-146, or my articles at Recommended long.] Some of the fatty acyl-CoA products from DNL escape packaging into VLDL for export and instead accumulate as lipid droplets in the hepatocyte (48), driving hepatic steatosis, similar to ethanol.  The end result is preventing normal insulin mediated … thus promoting insulin resistance.  {Disagree:  I hold based on ample journal articles that the process of glycation of which over 90% is from fructose damages the liver in ways that hinders it’s metabolic functions and that leads to insulin resistance in the liver.]  This drives hyperinsulinemia (51), with resultant obesity causing worsening insulin resistance. Furthermore, fructose increases the expression of FoxO1 (52). In the face of hepatic insulin resistance, FoxO1 is not phosphorylated to maintain its exclusion from the nucleus, with resultant transcription of gluconeogenic enzymes and hyperglycemia, requiring an even greater β-cell insulin response.

Hepatic metabolic profile and substrate burden: fructose vs. ethanol:  Thus, fructose and ethanol are analogous qualitatively in terms of hepatic metabolism. In small doses, neither will overwhelm hepatic mitochondrial capacity.   Both fructose and ethanol uniquely drive DNL, generating intrahepatic lipid, inflammation, and insulin resistance. Through the phenomena of enhanced DNL, JNK-1 activation, and hepatic insulin resistance, the hepatic metabolic profile of fructose is analogous to that of ethanol. Furthermore, fructose and ethanol are also analogous quantitatively.  [Can of beer equals a can of soda.]

ROS [reactive oxygen specie] formation and aging:  Any nutritional substrate with a free reactive aldehyde or ketone can induce ROS formation when that reactive moiety binds to an ε-amino group of lysine found in proteins or DNA bases or with a free hydroxyl group found in lipids.  Because glucose forms a 6-member glucopyranose (5 carbon ring with only 1 hydroxymethyl group), the ring form is stable, thereby reducing the availability of the free aldehyde [fructiose a 5-carbon ring].  However, fructose forms a 5-member fructofuranose ring with 2 axial hydroxymethyl groups, which forces fructose at greater frequency into its linear form with the free ketone moiety (60).

Effects of glucose:  Each glycation generates 1 superoxide radical that must be quenched by an antioxidant or cellular damage will occur (62). However, at 37°C and pH 7.4, the majority of glucose molecules are found in the stable 6-member glucopyranose ring form, limiting aldehyde exposure and reducing ROS generation.

Effects of ethanol:  Acetaldehyde induces hepatocellular damage through several different mechanisms (20), including mitochondrial damage, membrane effects, hypoxia, cytokine production, and iron mobilization.

Effects of fructose:  Because fructose forms a 5-member fructofuranose ring with steric hindrance from the 2 axial (abutting) hydroxymethyl groups, more molecules find themselves in the linear form, which exposes their reactive keto group and leads to fructation of proteins 7 times more rapidly than with glucose (64, 65). Thus, fructose-generated ROS species are abundant (66, 67) and require quenching by a hepatic antioxidant (e.g., glutathione) or hepatocellular damage will result (Fig. 4). The hepatotoxic effects of fructose via ROS formation have been demonstrated in both cultured hepatocytes (68) and animal models (69). Although mechanistic data in humans are difficult to obtain, case-control studies demonstrate that fructose consumption correlates with the development of hepatic steatosis and nonalcoholic steatohepatitis (7072).

Central nervous system effects to increase consumption:  The hedonic pathway that motivates the “reward” of food intake consists of the ventral tegmental area (VTA) (the home of the dopamine perikarya) and the nucleus accumbens (NA) (the destination of the dopamine axons, also referred to as the “pleasure center” of the brain). Food intake is a “readout” of the reward pathway; for example, administration of morphine to the NA increases food intake in a dose-dependent fashion (73). Dopamine neurotransmission from the VTA to the NA mediates the reward properties of food (74), whereas obesity results in decreased density of dopamine D2 receptors as measured by positron emission tomography scanning (75). Indeed, any process that reduces dopamine receptor density or occupancy can drive increased food intake and weight gain (76)….For both ethanol and fructose “Neuropharmacologic analyses demonstrate a reduction in D2 receptors in the NA, consistent with the fostering of reward and behavioral changes seen in addiction.

Conclusions

Most people consider sugar (i.e., fructose-containing compounds) to be just “empty calories.” However, this paper reports 3 separate ways that fructose exerts negative effects beyond its caloric equivalent. First, in the hypercaloric state, fructose drives DNL, resulting in dyslipidemia, hepatic steatosis, and insulin resistance, akin to that seen with ethanol. This should not be surprising because fructose and ethanol are congruent evolutionarily and biochemically. Ethanol is manufactured by the fermentation of fructose — the big difference is that for ethanol, the yeast performs the glycolysis, whereas for fructose, we humans perform our own glycolysis. Second, through production of reactive carbonyl moieties, both fructose and ethanol generate excess ROS, which increases the risk of hepatocellular damage if not quenched by antioxidants. Last, by downregulation of D2 receptors in the reward pathway, chronic fructose exposure contributes to a paradigm of continuous food intake independent of energy need and exerts symptoms of tolerance and withdrawal, similar to chronic ethanol abuse. Therefore, it should not be surprising that the disease profile of fructose and ethanol overconsumption would also be similar (Table 2).

Fructose also exhibits notable social and market similarities with ethanol. Both have been “fetishized” by various cultures in times past. Of course, today both sugar and alcohol are legal commodities and are traded freely. The problems of overuse and related health harm tend to occur in lower socioeconomic groups. Those who overconsume either substance are stigmatized. Finally, within public health circles, alcohol clearly evinces the 4 criteria of unavoidability, toxicity, abuse, and negative impact on society, which warrant consideration for personal intervention (e.g., “rehab”) and societal intervention (e.g., “laws”). Sucrose/HFCS satisfies those same 4 criteria as well (6).

Although fructose does not exhibit the same acute toxic effects of ethanol (i.e., central nervous system depression and resultant auto accidents), it recapitulates all the chronic toxic effects on long-term health. It is time for a paradigm shift in our societal treatment of fructose, recognizing that fructose is “alcohol without the buzz.”

 

Table 2.

Phenotypes of long-term energy substrate exposure1

Long-term ethanol exposure

Long-term fructose exposure

Hematologic disorders

Electrolyte abnormalities

Hypertension

Hypertension (uric acid)

Cardiac dilation

Cardiomyopathy

Myocardial infarction (dyslipidemia, insulin resistance)

Dyslipidemia

Dyslipidemia (de novo lipogenesis)

Pancreatitis

Pancreatitis (hypertriglyceridemia)

Obesity (insulin resistance)

Obesity (insulin resistance)

Malnutrition

Malnutrition (obesity)

Hepatic dysfunction (ASH)

Hepatic dysfunction (NASH)

Fetal alcohol syndrome

Addiction

Habituation, if not addiction

 

 

Footnotes

  • 1 Presented at the symposium “Fructose, Sucrose and High Fructose Corn Syrup. Modern Scientific Findings and Health Implications” held April 22, 2012 at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2012 in San Diego, CA. The symposium was sponsored by the American Society for Nutrition and supported in part by an educational grant from the Corn Refiners Association. A summary of the symposium “Fructose, Sucrose and High Fructose Corn Syrup. Modern Scientific Findings and Health Implications” was published in the September 2012 issue of Advances in Nutrition.

  • 2 Supported in part by NIDDK grant R01DK089216.

  • 3 Author disclosure: R. H. Lustig, no conflicts of interest.

  • 4 Abbreviations used: DNL, de novo lipogenesis; Foxo1, forkhead protein O1; HFCS, high-fructose corn syrup; IRS-1, insulin receptor substrate 1; JNK-1, c-jun N-terminal kinase 1; MKK7, MAP kinase kinase 7; MTP, microsomal transfer protein; NA, nucleus accumbens; NO, nitric oxide; ROS, reactive oxygen species; SREBP-1c, sterol regulatory element binding protein 1c; VTA, ventral tegmental area.

Literature Cited

1.        1.

 

United Nations General Assembly. Prevention and control of non-communicable diseases. UN General Assembly. New York, 2010.

2.        2.

 

1.        Chan JM, 

2.        Rimm EB, 

3.        Colditz GA, 

4.        Stampfer MJ, 

5.        Willett WC

. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men.Diabetes Care. 1994;17:9619.

 

Abstract/FREE Full Text

3.        3.

 

1.        Abbasi F, 

2.        Chu JW, 

3.        Lamendola C, 

4.        McLaughlin T, 

5.        Hayden J, 

6.        Reaven GM,

7.        Reaven PD

. Discrimination between obesity and insulin resistance in the relationship with adiponectin. Diabetes. 2004;53:58590.

Abstract/FREE Full Text

4.        4.

 

1.        Voulgari C, 

2.        Tentolouris N, 

3.        Dilaveris P, 

4.        Tousoulis D, 

5.        Katsilambros N,

6.        Stefanadis C

. Increased heart failure risk in normal-weight people with metabolic syndrome compared with metabolically healthy obese individuals. J Am Coll Cardiol. 2011;58:134350.

 

CrossRefMedline

5.        5.

 

1.        Vos MB, 

2.        Kimmons JE, 

3.        Gillespie C, 

4.        Welsh J, 

5.        Blanck HM

. Dietary fructose consumption among US children and adults: the Third National Health and Nutrition Examination Survey. Medscape J Med. 2008;10:160.

 

Medline

6.        6.

 

1.        Lustig RH, 

2.        Schmidt LA, 

3.        Brindis CD

. Public health: the toxic truth about sugar. Nature. 2012;482\7:279.

 

Search Google Scholar

7.        7.

 

1.        Frenette G, 

2.        Thabet M, 

3.        Sullivan R

. Polyol pathway in human epididymis and semen. J Androl. 2006;27:2339.

 

CrossRefMedline

8.        8.

 

1.        Newbrun E, 

2.        Hoover C, 

3.        Mettraux G, 

4.        Graf H

. Comparison of dietary habits and dental health of subjects with hereditary fructose intolerance and control subjects. J Am Dent Assoc. 1980;101:61926.

 

Abstract

9.        9.

 

1.        Burmeister LA, 

2.        Valdivia T, 

3.        Nuttall FQ

. Adult hereditary fructose intolerance.Arch Intern Med. 1991;151:7736.

 

CrossRefMedline

10.     10.

 

1.        Yasawy MI, 

2.        Folsch UR, 

3.        Schmidt WE, 

4.        Schwend M

. Adult hereditary fructose intolerance. World J Gastroenterol. 2009;15:24123.

 

CrossRefMedline

11.     11.

 

1.        Reaven GM

. The metabolic syndrome: is this diagnosis necessary? Am J Clin Nutr. 2006;83:123747.

 

Abstract/FREE Full Text

12.     12.

 

1.        Weiss R, 

2.        Bremer AA, 

3.        Lustig RH

. What is metabolic syndrome, and why are children getting it? In: Braaten D, editor. Year in Diabetes and Obesity, 2012. New York: Annals of the New York Academy of Science; 2013.

Search Google Scholar

13.     13.

 

1.        Brown MS, 

2.        Goldstein JL

. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab. 2008;7:956.

 

CrossRefMedline

14.     14.

 

1.        Naïmi M, 

2.        Gautier N, 

3.        Chaussade C, 

4.        Valverde AM, 

5.        Accili D, 

6.        Van Obberghen E

.Nuclear forkhead box O1 controls and integrates key signaling pathways in hepatocytes. Endocrinology. 2007;148:242434.

 

CrossRefMedline

15.     15.

 

1.        Dong XC, 

2.        Copps KD, 

3.        Guo S, 

4.        Li Y, 

5.        Kollipara R, 

6.        DePinho RA, 

7.        White MF

.Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab.2008;8:6576.

 

CrossRefMedline

16.     16.

 

1.        Biddinger SB, 

2.        Hernandez-Ono A, 

3.        Rask-Madsen C, 

4.        Haas JT, 

5.        Aleman JO,

6.        Suzuki R, 

7.        Scapa EF, 

8.        Agarwal C, 

9.        Carey MC, 

10.     Stephanopoulos G, 

11.     et al

. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab. 2008;7:12534.

 

CrossRefMedline

17.     17.

 

1.        Bremer AA, 

2.        Mietus-Snyder ML, 

3.        Lustig RH

. Toward a unifying hypothesis of metabolic syndrome. Pediatrics. 2012;129:55770.

 

Abstract/FREE Full Text

18.     18.

 

1.        Bizeau ME, 

2.        Pagliassotti MJ

. Hepatic adaptations to sucrose and fructose. Metabolism. 2005;54:1189201.

 

CrossRefMedline

19.     19.

 

1.        Farfán Labonne BE, 

2.        Gutiérrez M, 

3.        Gómez-Quiroz LE, 

4.        Konigsberg Fainstein M,

5.        Bucio L, 

6.        Souza V, 

7.        Flores O, 

8.        Ortíz V, 

9.        Hernández E, 

10.     Kershenobich D, 

11.     et al

.Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage. Cell Biol Toxicol. 2009;25:599609.

 

CrossRefMedline

20.     20.

 

1.        Dey A, 

2.        Cedarbaum AI

. Alcohol and oxidative liver injury. Hepatology.2006;43: Suppl 1:S6374.

 

CrossRefMedline

21.     21.

 

1.        Siler SQ, 

2.        Neese RA, 

3.        Hellerstein MK

. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am J Clin Nutr. 1999;70:92836.

 

Abstract/FREE Full Text

22.     22.

 

1.        You M, 

2.        Crabb DW

. Molecular mechanisms of alcoholic fatty liver: role of sterol regulatory element-binding proteins. Alcohol. 2004;34:3943.

 

CrossRefMedline

23.     23.

 

1.        Sozio M, 

2.        Crabb DW

. Alcohol and lipid metabolism. Am J Physiol Endocrinol Metab. 2008;295:E106.

 

Abstract/FREE Full Text

24.     24.

 

1.        Steinberg D, 

2.        Pearson TA, 

3.        Kuller LH

. Alcohol and atherosclerosis. Ann Intern Med. 1991;114:96776.

 

Medline

25.     25.

 

1.        Suter PM, 

2.        Schutz Y

. The effect of exercise, alcohol or both combined on health and physical performance. Int J Obes 2008;32 Suppl 6:S48–52.

Search Google Scholar

26.     26.

 

1.        Schneider J, 

2.        Tesdorfpf M, 

3.        Kaffarnik H, 

4.        Hausmann L, 

5.        Zöfel P, 

6.        Zilliken F

.Alteration of plasma lipids and intermediates of lipid metabolism in healthy fasting volunteers by ethanol and fructose. Res Exp Med (Berl).1976;167:15970.

 

CrossRefMedline

27.     27.

 

1.        Yokoyama H, 

2.        Hiroshi H, 

3.        Ohgo H, 

4.        Hibi T, 

5.        Saito I

. Effects of excessive ethanol consumption on the diagnosis of the metabolic syndrome using its clinical diagnostic criteria. Intern Med. 2007;46:134552.

 

CrossRefMedline

28.     28.

 

1.        Onishi Y, 

2.        Honda M, 

3.        Ogihara T, 

4.        Sakoda H, 

5.        Anai M, 

6.        Fujishiro M, 

7.        Ono H,

8.        Shojima N, 

9.        Fukushima Y, 

10.     Inukai K, 

11.     et al

. Ethanol feeding induces insulin resistance with enhanced PI 3-kinase activation. Biochem Biophys Res Commun.2003;303:78894.

 

CrossRefMedline

29.     29.

 

1.        Lee YJ, 

2.        Aroor AR, 

3.        Shukla SD

. Temporal activation of p42/44 mitogen-activated protein kinase and c-Jun N-terminal kinase by acetaldehyde in rat hepatocytes and its loss after chronic ethanol exposure. J Pharmacol Exp Ther.2002;301:90814.

 

Abstract/FREE Full Text

30.     30.

 

1.        Douard V, 

2.        Ferraris RP

. Regulation of the fructose transporter Glut5 in health and disease. Am J Physiol Endocrinol Metab. 2008;295:E22737.

Abstract/FREE Full Text

31.     31.

 

1.        Kim HS, 

2.        Paik HY, 

3.        Lee KU, 

4.        Lee HK, 

5.        Min HK

. Effects of several simple sugars on serum glucose and serum fructose levels in normal and diabetic subjects. Diabetes Res Clin Pract. 1988;4:2817.

 

CrossRefMedline

32.     32.

 

1.        Décombaz J, 

2.        Jentjens R, 

3.        Ith M, 

4.        Scheurer E, 

5.        Buehler T, 

6.        Jeukendrup A,

7.        Boesch C

. Fructose and galactose enhance postexercise human liver glycogen synthesis. Med Sci Sports Exerc. 2011;43:196471.

 

Medline

33.     33.

 

1.        Bonsignore A, 

2.        Pontremoli S, 

3.        Mangiarotti G, 

4.        De Flora A, 

5.        Mangiarotti M

. A direct interconversion: D-fructose 6-phosphate to sedoheptulose 7-phosphate and D-xylulose 5-phosphate catalyzed by the enzymes transketolase and transaldolase. J Biol Chem. 1962;237:3597602.

 

FREE Full Text

34.     34.

 

1.        Kabashima T, 

2.        Kawaguchi T, 

3.        Wadzinski BE, 

4.        Uyeda K

. Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver. Proc Natl Acad Sci U S A. 2003;100:510712.

Abstract/FREE Full Text

35.     35.

 

1.        Dentin R, 

2.        Benhamed F, 

3.        Hainault I, 

4.        Fauveau V, 

5.        Foufelle F, 

6.        Dyck JRB, 

7.        Girard J,

8.        Postic C

. Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice. Diabetes. 2006;55:215970.

Abstract/FREE Full Text

36.     36.

 

1.        Nagai Y, 

2.        Yonemitsu S, 

3.        Erion DM, 

4.        Iwasaki T, 

5.        Stark R, 

6.        Weismann D, 

7.        Dong J,

8.        Zhang D, 

9.        Jurczak MJ, 

10.     Löffler MG, 

11.     et al

. The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance. Cell Metab. 2009;9:25264.

 

CrossRefMedline

37.     37.

 

1.        Schwarz JM, 

2.        Noworolski SM, 

3.        Lee GA, 

4.        Wen M, 

5.        Dyachenko A, 

6.        Prior J,

7.        Weinberg M, 

8.        Herraiz L, 

9.        Rao M, 

10.     Mulligan K

, editors. Effects of short-term feeding with high- vs low-fructose isoenergetic diets on hepatic de novo lipogenesis, liver fat content and glucose regulation. Diabetes. 2009;58 suppl 1:4382, abstract 1476P.

 

Search Google Scholar

38.     38.

 

1.        Faeh D, 

2.        Minehira K, 

3.        Schwarz JM, 

4.        Periasami R, 

5.        Seongsu P, 

6.        Tappy L

. Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men. Diabetes. 2005;54:190713.

Abstract/FREE Full Text

39.     39.

 

1.        Stanhope KL, 

2.        Schwarz JM, 

3.        Keim NL, 

4.        Griffen SC, 

5.        Bremer AA, 

6.        Graham JL,

7.        Hatcher B, 

8.        Cox CL, 

9.        Dyachenko A, 

10.     Zhang W, 

11.     et al

. Consuming fructose-, not glucose-sweetened beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest.2009;119:132234.

 

CrossRefMedline

40.     40.

 

1.        Hudgins LC, 

2.        Parker TS, 

3.        Levine DM, 

4.        Hellerstein MK

. A dual sugar challenge test for lipogenic sensitivity to dietary fructose. J Clin Endocrinol Metab.2011;96:8618.

 

CrossRefMedline

41.     41.

 

1.        Teff KL, 

2.        Elliott SS, 

3.        Tschop M, 

4.        Kieffer TJ, 

5.        Rader D, 

6.        Heiman M, 

7.        Townsend RR,

8.        Keim NL, 

9.        D'Alessio D, 

10.     Havel PJ

. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab. 2004;89:296372.

 

CrossRefMedline

42.     42.

 

1.        Chong MF, 

2.        Fielding BA, 

3.        Frayn KN

. Mechanisms for the acute effect of fructose on postprandial lipemia. Am J Clin Nutr. 2007;85:151120.

Abstract/FREE Full Text

43.     43.

 

1.        Teff KL, 

2.        Grudziak J, 

3.        Townsend RR, 

4.        Dunn TN, 

5.        Grant RW, 

6.        Adams SH, 

7.        Keim NL,

8.        Cummings BP, 

9.        Stanhope KL, 

10.     Havel PJ

. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses. J Clin Endocrinol Metab. 2009;94:15629.

 

CrossRefMedline

44.     44.

 

1.        Aeberli I, 

2.        Zimmermann MB, 

3.        Molinari L, 

4.        Lehmann R, 

5.        l'Allemand D,

6.        Spinas GA, 

7.        Berneis K

. Fructose intake is a predictor of LDL particle size in overweight schoolchildren. Am J Clin Nutr. 2007;86:11748.

Abstract/FREE Full Text

45.     45.

 

1.        Hellerstein MK, 

2.        Schwarz JM, 

3.        Neese RA

. Regulation of hepatic de novo lipogenesis in humans. Annu Rev Nutr. 1996;16:52357.

 

CrossRefMedline

46.     46.

 

1.        Schwarz JM, 

2.        Linfoot P, 

3.        Dare D, 

4.        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;77:4350.

 

Abstract/FREE Full Text

47.     47.

 

1.         KA, 

2.        Ith M, 

3.        Kreis R, 

4.        Faeh D, 

5.        Bortolotti M, 

6.        Tran C, 

7.        Boesch C, 

8.        Tappy L

.Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am J Clin Nutr. 2009;89:17605.

 

Abstract/FREE Full Text

48.     48.

 

1.        Cave M, 

2.        Deaciuc I, 

3.        Mendez C, 

4.        Song Z, 

5.        Joshi-Barve S, 

6.        Barve S, 

7.        McClain C

.Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem. 2007;18:18495.

 

CrossRefMedline

49.     49.

 

1.        Samuel VT, 

2.        Liu ZX, 

3.        Qu X, 

4.        Elder BD, 

5.        Bilz S, 

6.        Befroy D, 

7.        Romanelli AJ,

8.        Shulman GI

. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem. 2004;279:3234553.

 

Abstract/FREE Full Text

50.     50.

 

1.        Tuncman G, 

2.        Hirosumi J, 

3.        Solinas G, 

4.        Chang L, 

5.        Karin M, 

6.        Hotamisligil GS

.Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci U S A. 2006;103:107416.

Abstract/FREE Full Text

51.     51.

 

1.        Kim SP, 

2.        Ellmerer M, 

3.        Van Citters GW, 

4.        Bergman RN

. Primacy of hepatic insulin resistance in the development of the metabolic syndrome induced by an isocaloric moderate-fat diet in the dog. Diabetes. 2003;52:245360.

Abstract/FREE Full Text

52.     52.

 

1.        Qu S, 

2.        Su D, 

3.        Altomonte J, 

4.        Kamagate A, 

5.        He J, 

6.        Perdomo G, 

7.        Tse T, 

8.        Jiang Y,

9.        Dong HH

. PPARα mediates the hypolipidemic action of fibrates by antagonizing FoxO1. Am J Physiol Endocrinol Metab. 2007;292:E42134.

Abstract/FREE Full Text

53.     53.

 

1.        Poitout V, 

2.        Robertson RP

. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev. 2008;29:35166.

 

CrossRefMedline

54.     54.

 

1.        Cnop M, 

2.        Igoillo-Esteve M, 

3.        Cunha DA, 

4.        Ladrière L, 

5.        Eizirik DL

. An update on lipotoxic endoplasmic reticulum stress in pancreatic beta-cells. Biochem Soc Trans. 2008;36:90915.

 

CrossRefMedline

55.     55.

 

1.        Liu M, 

2.        Hodish I, 

3.        Rhodes CJ, 

4.        Arvan P

. Proinsulin maturation, misfolding, and proteotoxicity. Proc Natl Acad Sci U S A. 2007;104:158416.

Abstract/FREE Full Text

56.     56.

 

1.        Hotamisligil GS

. Inflammation and endoplasmic reticulum stress in obesity and diabetes. Int J Obes. 2008;32 Suppl 7:S52–4.

 

Search Google Scholar

57.     57.

 

1.        Merksamer PI, 

2.        Trusina A, 

3.        Papa FR

. Real-time redox measurements during endoplasmic reticulum stress reveal interlinked protein folding functions. Cell.2008;135:93347.

 

CrossRefMedline

58.     58.

 

1.        Bergman RN, 

2.        Ader M, 

3.        Huecking K, 

4.        Van Citters G

. Accurate assessment of beta-cell function: the hyperbolic correction. Diabetes. 2002;51: Supp 1:S21220.

 

Abstract/FREE Full Text

59.     59.

 

1.        Lustig RH

. Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010;110:130721.

 

CrossRefMedline

60.     60.

 

1.        Lim JS, 

2.        Mietus-Snyder M, 

3.        Valente A, 

4.        Schwarz JM, 

5.        Lustig RH

. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol. 2010;7:25164.

 

CrossRefMedline

61.     61.

 

1.        Dills WL

. Protein fructosylation: fructose and the Maillard reaction. Am J Clin Nutr. 1993;58:779S87S.

 

Abstract/FREE Full Text

62.     62.

 

1.        Figueroa-Romero C, 

2.        Sadidi M, 

3.        Feldman EL

. Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord.2008;9:30114.

 

CrossRefMedline

63.     63.

 

1.        Niemelä O, 

2.        Parkkila S, 

3.        Ylä-Herttuala S, 

4.        Villanueva J, 

5.        Ruebner B, 

6.        Halsted CH

.Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease. Hepatology.1995;22:120814.

 

CrossRefMedline

64.     64.

 

1.        Ahmed N, 

2.        Furth AJ

. Failure of common glycation assays to detect glycation by fructose. Clin Chem. 1992;38:13013.

 

Abstract/FREE Full Text

65.     65.

 

1.        Schalkwijk CG, 

2.        Stehouwer CD, 

3.        van Hinsbergh VW

. Fructose-mediated non-enzymatic glycation: sweet coupling or bad modification. Diabetes Metab Res Rev. 2004;20:36982.

 

CrossRefMedline

66.     66.

 

1.        Bunn HF, 

2.        Higgins PJ

. Reaction of monosaccharides with proteins: possible evolutionary significance. Science. 1981;213:2224.

 

Abstract/FREE Full Text

67.     67.

 

1.        Bose T, 

2.        Chakraborti AS

. Fructose-induced structural and functional modifications of hemoglobin: implication for oxidative stress in diabetes mellitus. Biochim Biophys Acta. 2008;1780:8008.

 

Medline

68.     68.

 

1.        Lee O, 

2.        Bruce WR, 

3.        Dong Q, 

4.        Bruce J, 

5.        Mehta R, 

6.        O'Brien PJ

. Fructose and carbonyl metabolites and endogenous toxins. Chem Biol Interact.2009;178:3329.

 

CrossRefMedline

69.     69.

 

1.        Pickens MK, 

2.        Yan JS, 

3.        Ng RK, 

4.        Ogata H, 

5.        Grenert JP, 

6.        Beysen C, 

7.        Turner SM,

8.        Maher JJ

. Dietary sucrose is essential to the development of liver injury in the MCD model of steatohepatitis. J Lipid Res. 2009;50:207282.

Abstract/FREE Full Text

70.     70.

 

1.        Assy N, 

2.        Nasser G, 

3.        Kamayse I, 

4.        Nseir W, 

5.        Beniashvili Z, 

6.        Djibre A, 

7.        Grosovski M

.Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol. 2008;22:8116.

 

Medline

71.     71.

 

1.        Abid A, 

2.        Taha O, 

3.        Nseir W, 

4.        Farah R, 

5.        Grosovski M, 

6.        Assy N

. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome. J Hepatol. 2009;51:91824.

 

CrossRefMedline

72.     72.

 

1.        Abdelmalek MF, 

2.        Suzuki A, 

3.        Guy C, 

4.        Unalp-Arida A, 

5.        Colvin R, 

6.        Johnson RJ,

7.        Diehl AM

, Nonalcoholic Steatohepatitis Clinical Research Network. NSCR. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology. 2010;51:196171.

 

CrossRefMedline

73.     73.

 

1.        Kelley AE, 

2.        Bakshi VP, 

3.        Haber SN, 

4.        Steininger TL, 

5.        Will MJ, 

6.        Zhang M

. Opioid modulation of taste hedonics within the ventral striatum. Physiol Behav.2002;76:36577.

 

CrossRefMedline

74.     74.

 

1.        Carr KD, 

2.        Tsimberg Y, 

3.        Berman Y, 

4.        Yamamoto N

. Evidence of increased dopamine receptor signaling in food-restricted rats. Neuroscience.2003;119:115767.

 

CrossRefMedline

75.     75.

 

1.        Wang GJ, 

2.        Volkow ND, 

3.        Logan J, 

4.        Pappas NR, 

5.        Wong CT, 

6.        Zhu W, 

7.        Netusil N,

8.        Fowler JS

. Brain dopamine and obesity. Lancet. 2001;357:3547.

 

CrossRefMedline

76.     76.

 

1.        Stice E, 

2.        Spoor S, 

3.        Bohon C, 

4.        Small DM

. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science.2008;322:44952.

 

Abstract/FREE Full Text

77.     77.

 

1.        Colantuoni C, 

2.        Rada P, 

3.        McCarthy J, 

4.        Patten C, 

5.        Avena NM, 

6.        Chadeayne A,

7.        Hoebel BG

. Evidence that intermittent excessive sugar intake causes endogenous opioid dependence. Obes Res. 2002;10:47888.

 

Medline

78.     78.

 

1.        Koob GF, 

2.        Roberts AJ, 

3.        Schulteis G, 

4.        Parsons LH, 

5.        Heyser CJ, 

6.        Hyytiä P,

7.        Merlo-Pich E, 

8.        Weiss F

. Neurocircuitry targets in ethanol reward and dependence.Alcohol Clin Exp Res. 1998;22:39.

 

CrossRefMedline

79.     79.

 

1.        Melis M, 

2.        Diana M, 

3.        Enrico P, 

4.        Marinelli M, 

5.        Brodie MS

. Ethanol and acetaldehyde action on central dopamine systems: mechanisms, modulation, and relationship to stress. Alcohol. 2009;43:5319.

 

CrossRefMedline

80.     80.

 

1.        Philpot RM, 

2.        Wecker L, 

3.        Kirstein CL

. Repeated ethanol exposure during adolescence alters the developmental trajectory of dopaminergic output from the nucleus accumbens septi. Int J Dev Neurosci. 2009;27:80515.

 

CrossRefMedline

81.     81.

 

1.        Lind PA, 

2.        Eriksson CJ, 

3.        Wilhelmsen KC

. Association between harmful alcohol consumption behavior and dopamine transporter (DAT1) gene polymorphisms in a male Finnish population. Psychiatr Genet. 2009;19:11725.

 

CrossRefMedline

82.     82.

 

1.        Heinz A, 

2.        Beck A, 

3.        Grüsser SM, 

4.        Grace AA, 

5.        Wrase J

. Identifying the neural circuitry of alcohol craving and relapse vulnerability. Addict Biol.2009;14:10818.

 

CrossRefMedline

83.     83.

 

1.        Tupala E, 

2.        Tiihonen J

. Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:122147.

CrossRefMedline

84.     84.

 

1.        Erlanson-Albertsson C

. How palatable food disrupts appetite regulation.Basic Clin Pharmacol Toxicol. 2005;97:6173.

 

CrossRefMedline

85.     85.

 

1.        Pelchat ML

. Of human bondage: food craving, obsession, compulsion, and addiction. Physiol Behav. 2002;76:34752.

 

CrossRefMedline

86.     86.

 

1.        Spangler R, 

2.        Wittkowski KM, 

3.        Goddard NL, 

4.        Avena NM, 

5.        Hoebel BG,

6.        Leibowitz S

. F. Opiate-like effects of sugar on gene expression in reward areas of the rat brain. Brain Res Mol Brain Res. 2004;124:13442.

 

CrossRefMedline

87.     87.

 

1.        Pelchat ML, 

2.        Johnson A, 

3.        Chan R, 

4.        Valdez J, 

5.        Ragland JD

. Images of desire: food-craving activation during fMRI. Neuroimage. 2004;23:148693.

 

CrossRefMedline

88.     88.

 

1.        Avena NM, 

2.        Rada P, 

3.        Hoebel BG

. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32:2039.

 

CrossRefMedline

89.     89.

 

1.        Ifland JR, 

2.        Preuss HG, 

3.        Marcus MT, 

4.        Rourke KM, 

5.        Taylor WC, 

6.        Burau K,

7.        Jacobs WS, 

8.        Kadish W, 

9.        Manso G

. Refined food addiction: a classic substance use disorder. Med Hypotheses. 2009;72:51826.

 

CrossRefMedline

90.     90.

 

1.        Benton D

. The plausibility of sugar addiction and its role in obesity and eating disorders. Clin Nutr. 2010;29:288303.

 

CrossRefMedline

91.     91.

 

1.        Garber AK, 

2.        Lustig RH

. Is fast food addictive? Curr Drug Abuse Rev.2011;4:14662.

 

CrossRefMedline

92.     92.

 

1.        Ziauddeen H, 

2.        Farooqi ISFP

. Obesity and the brain: how convincing is the addiction model? Nat Rev Neurosci. 2012;13:27986.

 

CrossRefMedline

93.     93.

 

1.        Stanhope KL, 

2.        Griffen SC, 

3.        Bair BR, 

4.        Swarbrick MM, 

5.        Keim NL, 

6.        Havel PJ

. . Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. Am J Clin Nutr. 2008;87:1194203.

Abstract/FREE Full Text

94.     94.

 

1.        Bremer AA, 

2.        Stanhope KL, 

3.        Graham JL, 

4.        Cummings BP, 

5.        Wang W,

6.        Saville BR, Havel, PJ

. Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes. Clin Transl Sci.2011;4:24352.

 

CrossRefMedline

95.     95.

 

1.        Cozma AI, 

2.        Sievenpiper JL, 

3.        de Souza RJ, 

4.        Chiavaroli L, 

5.        Ha V, 

6.        Wang DD,

7.        Mirrahimi A, 

8.        Yu ME, 

9.        Carleton AJ, 

10.     Di Buono M, 

11.     et al

. Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials. Diabetes Care. 2012;35:161120.

 

Abstract/FREE Full Text

96.     96.

 

1.        Sievenpiper JL, 

2.        de Souza RJMA, 

3.        Yu ME, 

4.        Carleton AJ, 

5.        Beyene J, 

6.        Chiavaroli L,

7.        Di Buono M, 

8.        Jenkins AL, 

9.        Leiter LA, 

10.     Wolever TM, 

11.     et al

. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann Intern Med. 2012;156:291304.

 

Medline

97.     97.

 

1.        Rumessen JJ

. E. G-H. Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. Gut.1986;27:11618.

 

Abstract/FREE Full Text

98.     98.

 

1.        Parks EJ, 

2.        Krauss RM, 

3.        Christiansen MP, 

4.        Neese RA, 

5.        Hellerstein MK

. Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance. J Clin Invest. 1999;104:108796.

 

Medline

99.     99.

 

1.        Facchini F, 

2.        Chen YD, 

3.        Reaven GM

  • . Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity. Diabetes Care. 1994;17:115119.

Abstract/FREE Full Text

100.  100.

 

1.        Moore MC, 

2.        Davis SN, 

3.        Mann SL, 

4.        Cherrington AD

. Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes.Diabetes Care. 2001;24:18827.

 

Abstract/FREE Full Text

101.  101.

 

1.        Marriott BP, 

2.        Olsho L, 

3.        Hadden L, 

4.        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;50:22858.

CrossRefMedline 

Enter supporting content here

Looking for a topic, use Google Internal Search Engine

INTERNAL SITE SEARCH ENGINE by Google