While virtually absent in our diet a few hundred years ago, fructose has now become a major constituent of our modern diet. Our main sources of fructose are sucrose from beet or cane, high fructose corn syrup, fruits, and honey. Fructose has the same chemical formula as glucose (C(6)H(12)O(6)), but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. However, chronically high consumption of fructose in rodents leads to hepatic and extrahepatic insulin resistance, obesity, type 2 diabetes mellitus, and high blood pressure. The evidence is less compelling in humans, but high fructose intake has indeed been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Hepatic de novo lipogenesis and lipotoxicity, oxidative stress, and hyperuricemia have all been proposed as mechanisms responsible for these adverse metabolic effects of fructose. Although there is compelling evidence that very high fructose intake can have deleterious metabolic effects in humans as in rodents, the role of fructose in the development of the current epidemic of metabolic disorders remains controversial. Epidemiological studies show growing evidence that consumption of sweetened beverages (containing either sucrose or a mixture of glucose and fructose) is associated with a high energy intake, increased body weight, and the occurrence of metabolic and cardiovascular disorders. There is, however, no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects. There has also been much concern that consumption of free fructose, as provided in high fructose corn syrup, may cause more adverse effects than consumption of fructose consumed with sucrose. There is, however, no direct evidence for more serious metabolic consequences of high fructose corn syrup versus sucrose consumption.

http://www.perishablepundit.com/docs/fructose-and-obesity.pdf

Metabolic Effects of Fructose and the Worldwide Increase in Obesity

Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose tissue dysfunction in obesity and insulin resistance results in aberrant cytokine expression; many cytokines have a role in liver injury in NAFLD. Cellular stress and immune reactions, as well as the endocannabinoid system, have been implicated in animal models and in some human studies.

Nonalcoholic Fatty Liver Disease: Pathology and Pathogenesis

Treatment of NAFLD with diet, physical activity and exercise

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 novo lipogenesis 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 necroinflammation 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 role of fructose in the pathogenesis of NAFLD and the metabolic syndrome.

Aims/hypothesis
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liver-related complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardio-metabolic risk in NAFLD.

/pdf/impact-of-current-treatments-on-liver-disease-glucose-bf7lilponb.pdf

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

BACKGROUND: Little is known about dietary habits and their relationships with liver disease in nonalcoholic fatty liver disease (NAFLD) patients, particularly in the absence of obesity, diabetes or hyperlipidemia.

/pdf/soft-drink-consumption-linked-with-fatty-liver-in-the-1m1elurpc6.pdf

Soft drink consumption linked with fatty liver in the absence of traditional risk factors

https://www.journal-of-hepatology.eu/article/S0168-8278(09)00532-7/pdf

Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver, and increased hepatic triglyceride accumulation contributes to fatty liver. Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks, fructose 55% and glucose 45%. Soft drinks are the leading source of added sugar worldwide, and have been linked to obesity, diabetes, and metabolic syndrome. The consumption of soft drinks can increase the prevalence of NAFLD independently of metabolic syndrome. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose which increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potentially increase insulin resistance and inflammation. This review emphasizes some hard facts about soft drinks, reviews fructose metabolism, and explains how fructose contributes to the development of obesity, diabetes, metabolic syndrome, and NAFLD.

Soft drinks consumption and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of liver disease worldwide and has been recognized as a major health burden. The prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary lifestyle, unhealthy dietary pattern, and metabolic syndrome. Currently, there is no drug therapy that can be formulated for treating NAFLD. A combination of dietary modifications and increased physical activity remains the mainstay of NAFLD management. It is hard to maintain this mode of management; however, it seems to have significant long-term benefits. Furthermore, NAFLD patients, whether obese or not, should be educated that a healthy diet and physical activity have benefits beyond weight reduction. Further large controlled randomized trials are needed in order to identify the best dietary regimen and physical activity in the management of NAFLD patients. This review highlights the role of diet and lifestyle modifications in the management of NAFLD, and focuses on human studies regarding dietary modifications and physical activity.

Role of diet and lifestyle changes in nonalcoholic fatty liver disease

BACKGROUND Alopecia areata (AA) is an autoimmune disease, based on the response to local and/or systemic corticosteroid treatment. The role of vitamin D in the pathogenesis of immune/autoimmune mediated diseases has been widely studied. OBJECTIVES To investigate a possible association between serum 25-hydroxyvitamin D levels and alopecia areata. METHODS The study included 23 patients diagnosed with AA followed at our outpatient clinic during the period March 2010 to May 2011, as well as a control group matched for age and gender. All subjects underwent a complete work-up and medical examination, anthropometric measurements and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), and vitamin D levels. RESULTS Mean CRP values were significantly higher in the AA group than the control group (1.1 +/- 0.7 mg/dl vs. 0.4 +/- 0.8 mg/ dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group (11.32 +/- 10.18 ng/ml vs. 21.55 +/- 13.62 ng/ml in the control group, P < 0.05). Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval 2.6-4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95% CI 2.2-3.1, P = 0.02) were associated with AA. CONCLUSIONS We found a significant correlation between AA and vitamin D deficiency. Vitamin D deficiency can be a significant risk factor for AA occurrence.

William Nseir

Papers

Soft drink consumption linked with fatty liver in the absence of traditional risk factors

Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome.

Soft drinks consumption and nonalcoholic fatty liver disease.

Role of diet and lifestyle changes in nonalcoholic fatty liver disease

Association between vitamin D levels and alopecia areata.