Most of the calories in Europe and America diets come from fats and proteins, with carbohydrates accounting for about 40%. The grain are not the focus on the table. Instead, high-fructose syrup made from corn starch is widely used in processed foods. It is added to various snacks, such as bread, cakes, condiments and beverages. Moreover, sucrose, as a traditional sweetener, is still extensively used in food. It is hydrolyzed into glucose and fructose in our body. This ubiquitous fructose leads people to consume excess carbohydrates and cause damage without realizing it. In this article, we describe the difference between glucose and fructose, and introduce the intake, absorption, metabolism and health impacts of fructose: uncontrolled reaction rates (free radicals and reactive oxygen), easy accumulation of fat in liver, high lipid in blood and insulin resistance.
The structure: Fructose vs Glucose
Fructose is more easily consumed
The fructose in our diets not only come from fruits, but also from processed food, especially sweet snacks and beverages. Whether natural or processed, fructose attracts people to consume more food with its rich sweetness and pleasant taste. In addition, it doesn't prompt secretion of leptin and insulin to resist eating like glucose does. The result is a low sense of satiety, making it possible to consume more fructose at once.
Fructose is absorbed in the small intestine
Fructose can be directly absorbed, but sucrose must be broken down by enzymes. The GLUT5 protein is responsible for transporting fructose into small intestine cells. Because the low fructose concentration in our body, the energy-consuming sodium ion pump and ATP are not needed, and passive transport will suffice. This means limited absorption, and if too much fructose is ingested, some will stay in our intestine. The gas produced by fructose fermentation, the body fluid seeping out due to fructose osmotic pressure will result in stomach bloating and diarrhea. It is generally recommended not to exceed 50 grams in every meal.
Glucose is absorbed both actively and passively by transport proteins, without limited quantity. Active transport accompanies sodium ions that enter the cell by consuming electrical potential energy.
Fructose Metabolism vs. Glucose Metabolism
Glucose is phosphorylated twice in glycolysis. Not only does it consume energy (ATP), but the fructokinase PFK-1 is also regulated by ATP and citrate, thus controlling the chemical reaction not to proceed too rapidly. When the liver breaks down glucose at full blast, ample ATP and citrate inhibit liver cells from intaking glucose. This regulatory mechanism allows glucose enter the blood without being consumed by liver. As glucose is the primary fuel for all cells, our bodies are well-versed in regulating it. Various hormones, such as insulin and adrenaline, can regulate blood glucose levels. The glucose from starchy foods is used by oxygen-demanding organs like muscles and brain before fat synthesis. The excess glucose is converted into glycogen, and fat synthesis is in the last turn.
In contrast, fructose is metabolized in a completely different pathway that is much like an temporary metabolism for emergency. Low doses of fructose are metabolized by intestinal cells into glucose, lactate and glycerate. If the fructose exceed the intestinal capacity for digestion, the undigested is transported to liver. Unlike glucose, fructose does not start from the beginning of glycolysis, but enters at an intermediate step like a queue jumper. Another type of fructokinase (KHK) consume ATP to convert it into fructose-1-phosphate, which then enters the glycolysis. Thus, it successfully bypasses two rate-limiting enzymes and is not regulated by ATP or citrate. Liver cells absorb and metabolize fructose more quickly. Approximately 20% of the intermediate products are synthesized into glycogen, 20-50% are converted to glucose, and the rest are used for fat synthesis or oxidation. Long-term consumption of sugary drinks and sweet snacks leads to fat accumulation, especially around the abdomen and liver, as fructose is converted into fat faster and earlier than glucose. Long term excessive fructose intake also stimulates cells to produce more fatty acid synthase, exacerbating this condition. Without timely intervention, non-alcoholic fatty liver disease becomes a risk. In contrast, glucose is used up as cellular fuel, with fewer opportunities to be converted into fat.
Recently, researchers identified an enzyme (Triose Kinase, TK) that determine the fate of intermediate products. They found that cells knocked out the related gene produce more reactive oxygen (ROS) and synthesize less fatty acids during fructose metabolism. TK likely reduces fructose oxidation by activating fat synthesis, thereby it minimizes the damage caused by rapid chemical reactions. However, if too much fructose is consumed at once, it still depletes ATP in liver cells, and the excessive reactive oxygen and lactate leads to cellular toxicity.
Fructose and Inflammation, Lipids and Insulin Resistance
The interesting thing is that fructose doesn't cause blood glucose and insulin fluctuations, yet it still has the potential to make you suffer from insulin resistance, also known as type 2 diabetes. The benefits of replacing starch and glucose with fructose for blood glucose control are insufficient to offset its negative effects on lipids, fatty liver and diabetes.
Excessive fats and free radicals are among the reasons of cell damage and inflammation. Insulin resistance induced by fructose often occurs in liver cells first. Long-term excessive intake of fructose also keeps triglycerides and cholesterol levels high in the blood. Studies have shown that sugary drinks significantly increase triglycerides, C-reactive protein, interleukin-6 and tumor necrosis factor in blood. Fructose promotes fat accumulation all over the body, not only in subcutaneous tissue but also in muscles and organs. Disruption of fat metabolism and inflammation induce insulin resistance in all body cells. Lipotoxicity from high blood lipid levels also impairs the secretory function of pancreas cells. The reduction and resistance of insulin suppresses fat breakdown and is benefit for fat accumulation. It creates a vicious cycle that inevitably progresses to diabetes.