Fructose Abstracts 1

© 2011

Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease

            (Abdelmalek, Suzuki et al. 2010) Download

The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-matched controls. Because fructose elicits metabolic perturbations that may be hepatotoxic, we investigated the relationship between fructose consumption and disease severity in NAFLD. We studied 427 adults enrolled in the NASH Clinical Research Network for whom Block food questionnaire data were collected within 3 months of a liver biopsy. Fructose consumption was estimated based on reporting (frequency x amount) of Kool-aid, fruit juices, and nondietary soda intake, expressed as servings per week, and classified into none, minimum to moderate (<7 servings/week), and daily (> or =7 servings/week). The association of fructose intake with metabolic and histological features of NAFLD was analyzed using multiple linear and ordinal logistic regression analyses with and without controlling for other confounding factors. Increased fructose consumption was univariately associated with decreased age (P < 0.0001), male sex (P < 0.0001), hypertriglyceridemia (P < 0.04), low high-density lipoprotein (HDL) cholesterol (<0.0001), decreased serum glucose (P < 0.001), increased calorie intake (P < 0.0001), and hyperuricemia (P < 0.0001). After controlling for age, sex, BMI, and total calorie intake, daily fructose consumption was associated with lower steatosis grade and higher fibrosis stage (P < 0.05 for each). In older adults (age > or = 48 years), daily fructose consumption was associated with increased hepatic inflammation (P < 0.05) and hepatocyte ballooning (P = 0.05). CONCLUSION: In patients with NAFLD, daily fructose ingestion is associated with reduced hepatic steatosis but increased fibrosis. These results identify a readily modifiable environmental risk factor that may ameliorate disease progression in patients with NAFLD.

Non-Alcoholic Fatty Liver Disease and Fructose: Bad for Us, Better for Mice

            (Anania 2010) Download

The biochemical basis of hereditary fructose intolerance

            (Bouteldja and Timson 2010) Download

Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecular pathological consequences of mutation of the aldolase B gene.

Hereditary fructose intolerance and celiac disease: a novel genetic association

            (Ciacci, Gennarelli et al. 2006) Download

BACKGROUND & AIMS: Celiac disease (CD) has been associated with several genetic disorders, but has not been associated with hereditary fructose intolerance (HFI). METHODS: We identified CD in 4 female patients affected by HFI from among 38 Italian HFI patients. RESULTS: Three of these patients were children in whom the CD-associated signs were hypertransaminasemia, failure to thrive, low weight, and short stature, whereas the adult patient had protracted diarrhea notwithstanding a fructose-free diet. The incidence of CD in our group of HFI patients was higher (>10%) than in the general population (1%-3%) (P<.02). CONCLUSIONS: The possibility of an association between these 2 gastrointestinal disorders is important, particularly in the management of HFI patients with persisting symptoms.

Fructose intolerance in IBS and utility of fructose-restricted diet

            (Choi, Kraft et al. 2008) Download

INTRODUCTION: Whether dietary fructose intolerance causes symptoms of irritable bowel syndrome (IBS) is unclear. We examined the prevalence of fructose intolerance in IBS and long-term outcome of fructose-restricted diet. METHODS: Two hundred and nine patients with suspected IBS were retrospectively evaluated for organic illnesses. Patients with IBS (Rome II) and positive fructose breath test received instructions regarding fructose-restricted diet. One year later, their symptoms, compliance with, and effects of dietary modification on lifestyle were assessed using a structured interview. RESULTS: Eighty patients (m/f=26/54) fulfilled Rome II criteria. Of 80 patients, 31 (38%) had positive breath test. Of 31 patients, 26 (84%) participated in follow-up (mean=13 mo) evaluation. Of 26 patients, 14 (53%) were compliant with diet; mean compliance=71%. In this group, pain, belching, bloating, fullness, indigestion, and diarrhea improved (P<0.02). Of 26 patients, 12 (46%) were noncompliant, and their symptoms were unchanged, except belching. The mean impact on lifestyle, compliant versus noncompliant groups was 2.93 versus 2.57 (P>0.05). CONCLUSIONS: About one-third of patients with suspected IBS had fructose intolerance. When compliant, symptoms improved on fructose-restricted diet despite moderate impact on lifestyle; noncompliance was associated with persistent symptoms. Fructose intolerance is another jigsaw piece of the IBS puzzle that may respond to dietary modification.

Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome

            (Dekker, Su et al. 2010) Download

As dietary exposure to fructose has increased over the past 40 years, there is growing concern that high fructose consumption in humans may be in part responsible for the rising incidence of obesity worldwide. Obesity is associated with a host of metabolic challenges, collectively termed the metabolic syndrome. Fructose is a highly lipogenic sugar that has profound metabolic effects in the liver and has been associated with many of the components of the metabolic syndrome (insulin resistance, elevated waist circumference, dyslipidemia, and hypertension). Recent evidence has also uncovered effects of fructose in other tissues, including adipose tissue, the brain, and the gastrointestinal system, that may provide new insight into the metabolic consequences of high-fructose diets. Fructose feeding has now been shown to alter gene expression patterns (such as peroxisome proliferator-activated receptor-gamma coactivator-1alpha/beta in the liver), alter satiety factors in the brain, increase inflammation, reactive oxygen species, and portal endotoxin concentrations via Toll-like receptors, and induce leptin resistance. This review highlights recent findings in fructose feeding studies in both human and animal models with a focus on the molecular and biochemical mechanisms that underlie the development of insulin resistance, hepatic steatosis, and the metabolic syndrome.

Adverse effects of dietary fructose

            (Gaby 2005) Download

The consumption of fructose, primarily from high-fructose corn syrup (HFCS), has increased considerably in the United States during the past several decades. Intake of HFCS may now exceed that of the other major caloric sweetener, sucrose. Some nutritionists believe fructose is a safer form of sugar than sucrose, particularly for people with diabetes mellitus, because it does not adversely affect blood-glucose regulation, at least in the short-term. However, fructose has potentially harmful effects on other aspects of metabolism. In particular, fructose is a potent reducing sugar that promotes the formation of toxic advanced glycation end-products, which appear to play a role in the aging process; in the pathogenesis of the vascular, renal, and ocular complications of diabetes; and in the development of atherosclerosis. Fructose has also been implicated as the main cause of symptoms in some patients with chronic diarrhea or other functional bowel disturbances. In addition, excessive fructose consumption may be responsible in part for the increasing prevalence of obesity, diabetes mellitus, and non-alcoholic fatty liver disease. Although the long-term effects of fructose consumption have not been adequately studied in humans, the available evidence suggests it may be more harmful than is generally recognized. The extent to which a person might be adversely affected by dietary fructose depends both on the amount consumed and on individual tolerance. With a few exceptions, the relatively small amounts of fructose that occur naturally in fruits and vegetables are unlikely to have deleterious effects, and this review is not meant to discourage the consumption of these healthful foods.

Is medical nutrition therapy (MNT) the same for hereditary vs dietary fructose intolerance?

            (Marcason 2010) Download

Fructose consumption as a risk factor for non-alcoholic fatty liver disease

            (Ouyang, Cirillo et al. 2008) Download

BACKGROUND/AIMS: While the rise in non-alcoholic fatty liver disease (NAFLD) parallels the increase in obesity and diabetes, a significant increase in dietary fructose consumption in industrialized countries has also occurred. The increased consumption of high fructose corn syrup, primarily in the form of soft drinks, is linked with complications of the insulin resistance syndrome. Furthermore, the hepatic metabolism of fructose favors de novo lipogenesis and ATP depletion. We hypothesize that increased fructose consumption contributes to the development of NAFLD. METHODS: A dietary history and paired serum and liver tissue were obtained from patients with evidence of biopsy-proven NAFLD (n=49) without cirrhosis and controls (n=24) matched for gender, age (+/-5 years), and body mass index (+/-3 points). RESULTS: Consumption of fructose in patients with NAFLD was nearly 2- to 3-fold higher than controls [365 kcal vs 170 kcal (p<0.05)]. In patients with NAFLD (n=6), hepatic mRNA expression of fructokinase (KHK), an important enzyme for fructose metabolism, and fatty acid synthase, an important enzyme for lipogenesis were increased (p=0.04 and p=0.02, respectively). In an AML hepatocyte cell line, fructose resulted in dose-dependent increase in KHK protein and activity. CONCLUSIONS: The pathogenic mechanism underlying the development of NAFLD may be associated with excessive dietary fructose consumption.

Dietary fructose intolerance in children and adolescents

            (Tsampalieros, Beauchamp et al. 2008) Download

Protective effect of bile acids on the onset of fructose-induced hepatic steatosis in mice

            (Volynets, Spruss et al. 2010) Download

Fructose intake is being discussed as a key dietary factor in the development of nonalcoholic fatty liver disease (NAFLD). Bile acids have been shown to modulate energy metabolism. We tested the effects of bile acids on fructose-induced hepatic steatosis. In C57BL/6J mice treated with a combination of chenodeoxycholic acid and cholic acid (100 mg/kg body weight each) while drinking water or a 30% fructose solution for eight weeks and appropriate controls, markers of hepatic steatosis, portal endotoxin levels, and markers of hepatic lipogenesis were determined. In mice concomitantly treated with bile acids, the onset of fructose-induced hepatic steatosis was markedly attenuated compared to mice only fed fructose. The protective effects of the bile acid treatment were associated with a downregulation of tumor necrosis factor (TNF)alpha, sterol regulatory element-binding protein (SREBP)1, FAS mRNA expression, and lipid peroxidation in the liver, whereas hepatic farnesoid X receptor (FXR) or short heterodimer partner (SHP) protein concentration did not differ between groups fed fructose. Rather, bile acid treatment normalized occludin protein concentration in the duodenum, portal endotoxin levels, and markers of Kupffer cell activation to the level of water controls. Taken together, these data suggest that bile acids prevent fructose-induced hepatic steatosis in mice through mechanisms involving protection against the fructose-induced translocation of intestinal bacterial endotoxin.

Fructose and cardiometabolic disorders: the controversy will, and must, continue

            (Wiernsperger, Geloen et al. 2010) Download

The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit.Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.

Adult hereditary fructose intolerance

         (Yasawy, Folsch et al. 2009) Download

Hereditary fructose intolerance (HFI) is an under-recognized, preventable life-threatening condition. It is an autosomal recessive disorder with subnormal activity of aldolase B in the liver, kidney and small bowel. Symptoms are present only after the ingestion of fructose, which leads to brisk hypoglycemia, and an individual with continued ingestion will exhibit vomiting, abdominal pain, failure to thrive, and renal and liver failure. A diagnosis of HFI was made in a 50-year-old woman on the basis of medical history, response to IV fructose intolerance test, demonstration of aldolase B activity reduction in duodenal biopsy, and molecular analysis of leukocyte DNA by PCR showed homozygosity for two doses of mutant gene. HFI may remain undiagnosed until adult life and may lead to disastrous complications following inadvertent fructose or sorbitol infusion. Several lethal episodes of HFI following sorbitol and fructose infusion have been reported. The diagnosis can only be suspected by taking a careful dietary history, and this can present serious complications.

Nutritional modulation of nonalcoholic fatty liver disease and insulin resistance: human data

            (Yki-Jarvinen 2010) Download

PURPOSE OF REVIEW: Concomitant with the obesity epidemic, a fatty liver due to nonalcoholic causes has become the most common liver disorder. Nonalcoholic fatty liver disease (NAFLD) covers a range from benign steatosis to nonalcoholic steatohepatitis (NASH), which in turn may progress to cirrhosis. NAFLD predicts, independent of obesity, the metabolic syndrome and type 2 diabetes and can progress to cirrhosis. This review focuses on studies in humans addressing effects of dietary changes in NAFLD. RECENT FINDINGS: Cross-sectionally, increased intake of fructose and simple sugars characterizes patients with NAFLD compared with weight-matched controls. Increased fructose intake is also associated with hepatic insulin resistance and fibrosis severity in NASH. Intake of saturated fat may also be increased in NAFLD. Dietary intervention studies have shown that liver volume and fat content changes significantly within a few days in response to caloric restriction or excess despite no or small changes in body weight. Weight loss by bariatric surgery decreases liver fat and inflammation but effects on fibrosis are uncertain. Hepatic insulin sensitivity generally changes in parallel with changes in liver fat content in NAFLD. Human data are limited regarding effects of isocaloric changes in diet composition on liver fat content. SUMMARY: Maintenance of normal body weight and avoidance of intake of excess lipogenic simple sugars would seem beneficial for prevention of NAFLD and its metabolic consequences.


Abdelmalek, M. F., A. Suzuki, et al. (2010). "Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease." Hepatology 51(6): 1961-71.

Anania, F. A. (2010). "Non-Alcoholic Fatty Liver Disease and Fructose: Bad for Us, Better for Mice." J Hepatol.

Bouteldja, N. and D. J. Timson (2010). "The biochemical basis of hereditary fructose intolerance." J Inherit Metab Dis 33(2): 105-12.

Choi, Y. K., N. Kraft, et al. (2008). "Fructose intolerance in IBS and utility of fructose-restricted diet." J Clin Gastroenterol 42(3): 233-8.

Ciacci, C., D. Gennarelli, et al. (2006). "Hereditary fructose intolerance and celiac disease: a novel genetic association." Clin Gastroenterol Hepatol 4(5): 635-8.

Dekker, M. J., Q. Su, et al. (2010). "Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome." Am J Physiol Endocrinol Metab 299(5): E685-94.

Gaby, A. R. (2005). "Adverse effects of dietary fructose." Altern Med Rev 10(4): 294-306.

Marcason, W. (2010). "Is medical nutrition therapy (MNT) the same for hereditary vs dietary fructose intolerance?" J Am Diet Assoc 110(7): 1128.

Ouyang, X., P. Cirillo, et al. (2008). "Fructose consumption as a risk factor for non-alcoholic fatty liver disease." J Hepatol 48(6): 993-9.

Tsampalieros, A., J. Beauchamp, et al. (2008). "Dietary fructose intolerance in children and adolescents." Arch Dis Child 93(12): 1078.

Volynets, V., A. Spruss, et al. (2010). "Protective effect of bile acids on the onset of fructose-induced hepatic steatosis in mice." J Lipid Res 51(12): 3414-24.

Wiernsperger, N., A. Geloen, et al. (2010). "Fructose and cardiometabolic disorders: the controversy will, and must, continue." Clinics (Sao Paulo) 65(7): 729-38.

Yasawy, M. I., U. R. Folsch, et al. (2009). "Adult hereditary fructose intolerance." World J Gastroenterol 15(19): 2412-3.

Yki-Jarvinen, H. (2010). "Nutritional modulation of nonalcoholic fatty liver disease and insulin resistance: human data." Curr Opin Clin Nutr Metab Care 13(6): 709-14.