The Differences Between Honey With Natural Sugar And High Fructose Corn Syrup

The human body cannot differentiate between natural sugar found in honey, or milk and processed sugar. All sugars are treated and digested in the similar way, even though there are several significant differences in their metabolism. While carbohydrate digestion begins in the mouth, the small intestine is the main part of digestion and absorption. First, polysaccharides are degraded to disaccharides and then monosaccharides, which are moved to the liver for additional metabolism. Small intestine and liver convert the monosaccharides galactose and fructose for further metabolism (20). It has been suggested that fructose is important in modulating metabolism in liver when consumed in a small, catalytic amounts with orally ingested glucose. This modulation occurs by increasing hepatic glycogen synthesis in human subjects and reduces glycemic responses in subjects with type 2 diabetes mellitus. However, when large amounts of fructose are ingested, they provide a relatively unregulated source of carbon precursors for hepatic lipogenesis.

 The metabolism of fructose differs from that of glucose in several other ways as well. In most tissues, glucose enters cells by insulin dependent transport mechanism (Glut-4). Insulin activates the insulin receptor, which in turn increases the density of glucose transporters on the cell surface and thus facilitates glucose entry. Once inside the cell, glucose is phosphorylated to glucose-6-phosphate by the action of glucokinase, then intracellular metabolism of glucose begins. After that, Intracellular enzymes can tightly control conversion of glucose-6-phosphate to the glycerol backbone of Actually, the Glucose-6-phosphate has two major fates: storage in the form of glycogen or conversion to fructose-6-phosphate through phosphoglucoseisomerase. Additionally, fructose-6-phosphate is phosphorylated by phosphofructokinase (PFK) in order to produce fructose-1, 6-bisphosphate. Phosphofructokinase is the major rate-limiting process in glycolysis. Aldolase, as occur in fructose metabolism, will play an important role to convert fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. The metabolic fate of glucose depends mainly on the body’s energy needs. The integrated pathways of glucose metabolism include glycolysis, glycogenolysis, glycogenesis, lipogenesis, the pentose phosphate pathway, and the tricarboxylic acid cycle (41).

In contrast with glucose, Fructose metabolism is illustrated by knowing three major enzymes which are fructokinase, fructose-bisphosphate aldolase B, and adenosine triphosphate (ATP)-dependent dihydroxyacetone kinase (or triokinase). They only found in the liver. In the liver, fructose is converted to fructose 1-phosphate through fructokinase rather than fructose-6-phosphate. It is very important to demonstrate that since the liver does not contain hexokinase, it cannot phosphorylate fructose to fructose-6- phosphate (20). After that, fructose 1-phosphate is converted into the trioses dihydroxyacetone phosphate and glyceraldehyde by aldolase B. Moreover, aldolase B utilizes in the liver for the glycolysis (glucose metabolism). Besides, glyceraldehyde is converted to glyceraldehyde-3-phosphate through triokinase. Until this stage of fructose metabolism, there is no rate-limiting steps. Thus, there is a large amount of substrate causing metabolic pathways from triose phosphate such as glyconeogenesis, glycogenesis,glycolysis, fatty acid esterification, and lipogenesis. After that, glyceraldehyde- 3-phosphate is metabolized to pyruvate through, pyruvate kinase, which is the rate-limiting enzyme. Finally, fructose enhances the activation of pyruvate kinase and that causing increasing flux of pyruvate into TCA cycle (41). Fructose enters cells via a Glut-5 transporter that is not insulin dependent. This transporter does not exist in the brain and pancreatic β cells, which indicates limited entry of fructose into these tissues. Glucose is used for muscular activity and it is the main source of brain’s energy unlike the fructose. Fructose cannot provide energy source of brain or muscle (20). Once inside the cell, fructose is phosphorylated to form fructose-1-phosphate. In this configuration, fructose is readily cleaved by aldolase to form trioses that are the backbone for phospholipid and triacylglycerol synthesis. Fructose also provides carbon atoms for synthesis of long-chain fatty acids, although in humans, the quantity of these carbon atoms is small. Thus, fructose facilitates the biochemical formation of triacylglycerol more efficiently than does glucose. For instance, when a diet, 17% fructose, was provided to healthy men and women, only men, displayed significant increase of 32% in plasma triacylglycerol concentrations (38).

As mentioned earlier, fructose metabolism differs from glucose significantly in two main ways. First, there is almost complete hepatic extraction of fructose. Besides, there are different enzymatic reactions in the initial steps of the metabolism of fructose and glucose. These differences in hepatic metabolism can cause different effects of fructose comparing with glucose in long and short-term effects. Nevertheless, it is very important to indicate that the metabolic pathways in liver for glucose and fructose are interactive. When fructose is metabolized in liver, it is converted to carbon dioxide, glycogen, glucose, and lactate. A small amount of fructose is metabolized to carbon dioxide while around 50% of fructose is converted to glucose in liver, 15% to 18% to glycogen, and 25% to lactate. Moreover, depending on metabolic and nutritional status of individuals, a few percentage of fructose is converted to free fatty acids. According to several studies, there is an argument by some researchers about the fact when glucose and fructose are consumed together, that cause increase in free fatty acid by de novo lipogenesis (DNL). This is based on that glucose dominates the glycogenetic pathway, and therefore fructose will be convert to FFA. However, most research in this area does not agree with DNL. On the other hand, the metabolic pathways associated with DNL also inhibit the oxidation of FFA. It has been indicated that 1% to 3% of VLDL produced in people who are consuming a normal Western diet is because of DNL (24).

To sum up, almost all fructose-containing nutritive sweeteners seem to reach the same intestinal sites for absorption as monosaccharides. For instance, fruit sugars, honey, and HFCS. However, a small amount of polysaccharide glucose in HFCS is rapidly broken down to free glucose by intestinal and salivary amylases. Glucose is absorbed into the portal blood through an active, energy-requiring mechanism mediated by sodium and a specific glucose transport protein (GLUT-2) and an active sodium/glucose cotransporter (SGLT) (22, 41). GLUT-2 shows a low affinity for fructose, and it is responsible for only a small part of the total fructose absorption. In contrast, many researchers indicated that intestinal fructose absorption is incomplete in humans (41). Fructose is absorbed via the sodium independent GLUT-5 (a fructose-specific hexose) transporter by facilitated diffusion. In addition, disaccharide sucrose needs to be hydrolyzed before absorption by a plentiful sucrase in the brush border (22.21) in order to produce one molecule of glucose and one of fructose. Additionally, this transporter is found in the jejunum on the brush border membranes. It has been proposed that upon entry into the enterocyte, fructose is converted to fructose-1-phosphate in order to maintain a high concentration for continued fructose diffusion. Fructose enters the portal circulation from the enterocytes through the basolateral transporter, GLUT2, which also transports glucose and galactose. Furthermore, the expression of GLUT5 will increase within hours of consuming a high fructose diet, showing that the transporter is regulated by luminal signals, particularly fructose. However, consumption of a large amount of pure fructose can exceed the ability of intestinal fructose absorption causing diarrhea. This is issue is very common in young children who consume a large quantity of dietary fructose, and in individuals whom GLUT5 expression is constrained by developmental stage. Fructose malabsorption is a pediatric disease associated to developmental limitations of GLUT5 expression even though it is rare. In adults, the malabsorption of fructose is believed to be linked to the insufficient upregulation of GLUT5 (21). When reaching to the liver through the portal circulation, hepatic glucose metabolism is regulated by phosphofructokinase, which is inhibited by ATP and citrate when the hepatic energy status is high, thus limiting the hepatic uptake of dietary glucose. As a result, that allows much of the ingested glucose arriving via the portal vein to bypass the liver and reach the systemic circulation causing to increased circulating glucose and glucose-stimulated insulin concentrations. On the other hand, the initial phosphorylation of dietary fructose is mainly catalyzed by fructokinase, which is not regulated by the hepatic energy status. This causes to unregulated fructose uptake by the liver, causing in most of the ingested fructose metabolized in the liver and a small amount reaching the systemic circulation. In fact, this is revealed what happened in the 24 h consuming fructose and glucose in subjects who take, with three meals, glucose or fructose sweetened beverages. In case of consuming fructose-sweetened beverages, post meal fructose peaks increased by less than 0.4 mmol while glucose-sweetened beverages increased over fasting levels by 4–5 mmol. Some tissues such as adipose tissues skeletal muscles, and kidneys can take up a very small amount of fructose that bypass the liver. Moreover, in a very low level, the GLUT5 transporter is expressed in these tissues.

Most importantly, the unregulated hepatic uptake of a large amount of fructose leads in increased producing of lipogenic precursors, thus causing to increased de novo lipogenesis (DNL). DNL increases the intrahepatic lipid supply indirectly via inhibiting fatty acid oxidation or directly through synthesis of fatty acids. Therefore, increased production of intrahepatic lipids leads to increasing secretion of very-low-density lipoprotein (VLDL), particularly VLDL1 which is the large VLDL particles that take more TG than VLDL2 (small particles) particles. Thus, increased production of VLVL1 causing dyslipidemia, which is the characteristic of patients with metabolic syndrome and type 2 diabetes. On the other hand, accumulation of intrahepatic lipids can lead to hepatic insulin resistance, perhaps by increasing the production of diacylglycerol, which activates novel protein kinase C (nPKC) and that causes to serine phosphorylation (serine P) of the insulin receptor and insulin receptor substrate 1 (IRS1) and therefore impaired insulin action (21).

Currently, HFCS used in beverages contains 55% fructose made by industrial enzymatic isomerization (28). A great alternative of HFCS is rare sugars such as tagatose and allulose. In fact, food industry do not use those rare sugars in their products, although they exhibit many benefits particularly as potential anti-diabetic and anti-obesity, because the cost of rare sugars would be much higher than HFSC. However, in order to overcome this issue, a group of researchers at UIUC engineered the yeast strain, which produces tagatose in much larger quantities comparing to traditional enzymatic manufacturing techniques and therefore that will contribute to make tagatose a cost-effective alternative to sugar or high-fructose corn syrup (30). D- tagatose is promising sweetener without major adverse effects observed in several clinical studies (42).

References:

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