Fructose

Etymology

The word "fructose" was coined in 1857 from the Latin for fructus (fruit) and the generic chemical suffix for sugars, -ose. It is also called fruit sugar and levulose or laevulose, due to its ability to rotate plane polarised light in a laevorotary fashion (anti-clockwise/to the left) when a beam is shone through it in solution. Likewise, dextrose (an isomer of glucose) is given its name due to its ability to rotate plane polarised light in a dextrorotary fashion (clockwise/to the right).

Chemical structure

Fructose adopts both cyclic six- and five-membered structure, The six membered ring can exist as either the β-d-fructopyranose and α-d-fructopyranose. The five-membered rings exists as either of two isomers β-d-fructofuranose and α-d-fructofuranose. Additionally, an acyclic (open-chain) form exists: keto-d-fructose. At 70% and 22% respectively, fructopyranose and fructofuranose are the dominant species in aqueous solution.

Chemical reactions

Fructose and fermentation

Fructose may be anaerobically fermented by yeast and bacteria. Yeast enzymes convert sugar (sucrose, glucose, and fructose, but not lactose) to ethanol and carbon dioxide. Some of the carbon dioxide produced during fermentation will remain dissolved in water, where it will reach equilibrium with carbonic acid. The dissolved carbon dioxide and carbonic acid produce the carbonation in some fermented beverages, such as champagne.

Fructose and Maillard reaction

Fructose undergoes the Maillard reaction, non-enzymatic browning, with amino acids. Because fructose exists to a greater extent in the open-chain form than does glucose, the initial stages of the Maillard reaction occur more rapidly than with glucose. Therefore, fructose has potential to contribute to changes in food palatability, as well as other nutritional effects, such as excessive browning, volume and tenderness reduction during cake preparation, and formation of mutagenic compounds.

Dehydration

Fructose can be dehydrated to give hydroxymethylfurfural ("HMF", C
₆H
₆O
₃), which can be processed into liquid dimethylfuran (C
₆H
₈O). This conversion has long been proposed, not implemented, as a route to green fuels.

Physical and functional properties

Sweetness of fructose

The primary reason that fructose is used commercially in foods and beverages, besides its low cost, is its high relative sweetness. It is the sweetest of all naturally occurring carbohydrates. The relative sweetness of fructose has been reported in the range of 1.2–1.8 times that of sucrose. However, it is the 6-membered ring form of fructose that is sweeter; the 5-membered ring form tastes about the same as usual table sugar. Warming fructose leads to formation of the 5-membered ring form. Therefore, the relative sweetness decreases with increasing temperature. However, it has been observed that the absolute sweetness of fructose is identical at 5 °C as 50 °C and thus the relative sweetness to sucrose is not due to anomeric distribution but a decrease in the absolute sweetness of sucrose at higher temperatures.

The sweetness of fructose is perceived earlier than that of sucrose or glucose, and the taste sensation reaches a peak (higher than that of sucrose), and diminishes more quickly than that of sucrose. Fructose can also enhance other flavors in the system.

Fructose exhibits a sweetness synergy effect when used in combination with other sweeteners. The relative sweetness of fructose blended with sucrose, aspartame, or saccharin is perceived to be greater than the sweetness calculated from individual components.

Fructose solubility and crystallization

Fructose has higher water solubility than other sugars, as well as other sugar alcohols. Fructose is, therefore, difficult to crystallize from an aqueous solution. Sugar mixes containing fructose, such as candies, are softer than those containing other sugars because of the greater solubility of fructose.

Fructose hygroscopicity and humectancy

Fructose is quicker to absorb moisture and slower to release it to the environment than sucrose, glucose, or other nutritive sweeteners. Fructose is an excellent humectant and retains moisture for a long period of time even at low relative humidity (RH). Therefore, fructose can contribute a more palatable texture, and longer shelf life to the food products in which it is used.

Freezing point

Fructose has a greater effect on freezing point depression than disaccharides or oligosaccharides, which may protect the integrity of cell walls of fruit by reducing ice crystal formation. However, this characteristic may be undesirable in soft-serve or hard-frozen dairy desserts.

Fructose and starch functionality in food systems

Fructose increases starch viscosity more rapidly and achieves a higher final viscosity than sucrose because fructose lowers the temperature required during gelatinizing of starch, causing a greater final viscosity.

Although some artificial sweeteners are not suitable for home baking, many traditional recipes use fructose.

Fructose digestion and absorption in humans

Fructose exists in foods either as a monosaccharide (free fructose) or as a unit of a disaccharide (sucrose). Free fructose is a ketonic simple sugar and one of the three dietary monosaccharides absorbed directly by the intestine. When fructose is consumed in the form of sucrose, it is digested (broken down) and then absorbed as free fructose. As sucrose comes into contact with the membrane of the small intestine, the enzyme sucrase catalyzes the cleavage of sucrose to yield one glucose unit and one fructose unit, which are then each absorbed. After absorption, it enters the hepatic portal vein and is directed toward the liver.

The mechanism of fructose absorption in the small intestine is not completely understood. Some evidence suggests active transport, because fructose uptake has been shown to occur against a concentration gradient. However, the majority of research supports the claim that fructose absorption occurs on the mucosal membrane via facilitated transport involving GLUT5 transport proteins. Since the concentration of fructose is higher in the lumen, fructose is able to flow down a concentration gradient into the enterocytes, assisted by transport proteins. Fructose may be transported out of the enterocyte across the basolateral membrane by either GLUT2 or GLUT5, although the GLUT2 transporter has a greater capacity for transporting fructose, and, therefore, the majority of fructose is transported out of the enterocyte through GLUT2.

Capacity and rate of absorption

The absorption capacity for fructose in monosaccharide form ranges from less than 5 g to 50 g (per individual serving) and adapts with changes in dietary fructose intake. Studies show the greatest absorption rate occurs when glucose and fructose are administered in equal quantities. When fructose is ingested as part of the disaccharide sucrose, absorption capacity is much higher because fructose exists in a 1:1 ratio with glucose. It appears that the GLUT5 transfer rate may be saturated at low levels, and absorption is increased through joint absorption with glucose. One proposed mechanism for this phenomenon is a glucose-dependent cotransport of fructose.

In addition, fructose transfer activity increases with dietary fructose intake. The presence of fructose in the lumen causes increased mRNA transcription of GLUT5, leading to increased transport proteins. High-fructose diets (>2.4 g/kg body wt) increase the transport proteins within three days of intake.

Malabsorption

Several studies have measured the intestinal absorption of fructose using the hydrogen breath test. These studies indicate that fructose is not completely absorbed in the small intestine. When fructose is not absorbed in the small intestine, it is transported into the large intestine, where it is fermented by the colonic flora. Hydrogen is produced during the fermentation process and dissolves into the blood of the portal vein. This hydrogen is transported to the lungs, where it is exchanged across the lungs and is measurable by the hydrogen breath test. The colonic flora also produces carbon dioxide, short-chain fatty acids, organic acids, and trace gases in the presence of unabsorbed fructose. The presence of gases and organic acids in the large intestine causes gastrointestinal symptoms such as bloating, diarrhea, flatulence, and gastrointestinal pain. Exercise immediately after consumption can exacerbate these symptoms by decreasing transit time in the small intestine, resulting in a greater amount of fructose emptied into the large intestine.

Fructose metabolism

The liver converts most fructose and galactose into glucose for distribution in the bloodstream or deposition into glycogen.

All three dietary monosaccharides are transported into the liver by the GLUT2 transporter. Fructose and galactose are phosphorylated in the liver by fructokinase (K_m= 0.5 mM) and galactokinase (K_m = 0.8 mM), respectively. By contrast, glucose tends to pass through the liver (K_m of hepatic glucokinase = 10 mM) and can be metabolised anywhere in the body. Uptake of fructose by the liver is not regulated by insulin. However, insulin is capable of increasing the abundance and functional activity of GLUT5, fructose transporter, in skeletal muscle cells.

Fructolysis

The initial catabolism of fructose is sometimes referred to as fructolysis, in analogy with glycolysis, the catabolism of glucose. In fructolysis, the enzyme fructokinase initially produces fructose 1-phosphate, which is split by aldolase B to produce the trioses dihydroxyacetone phosphate (DHAP) and glyceraldehyde. Unlike glycolysis, in fructolysis the triose glyceraldehyde lacks a phosphate group. A third enzyme, triokinase, is therefore required to phosphorylate glyceraldehyde, producing glyceraldehyde 3-phosphate. The resulting trioses are identical to those obtained in glycolysis and can enter the gluconeogenic pathway for glucose or glycogen synthesis, or be further catabolized through the lower glycolytic pathway to pyruvate.

Metabolism of fructose to DHAP and glyceraldehyde

The first step in the metabolism of fructose is the phosphorylation of fructose to fructose 1-phosphate by fructokinase, thus trapping fructose for metabolism in the liver. Fructose 1-phosphate then undergoes hydrolysis by aldolase B to form DHAP and glyceraldehydes; DHAP can either be isomerized to glyceraldehyde 3-phosphate by triosephosphate isomerase or undergo reduction to glycerol 3-phosphate by glycerol 3-phosphate dehydrogenase. The glyceraldehyde produced may also be converted to glyceraldehyde 3-phosphate by glyceraldehyde kinase or further converted to glycerol 3-phosphate by glycerol 3-phosphate dehydrogenase. The metabolism of fructose at this point yields intermediates in the gluconeogenic pathway leading to glycogen synthesis as well as fatty acid and triglyceride synthesis.

Synthesis of glycogen from DHAP and glyceraldehyde 3-phosphate

The resultant glyceraldehyde formed by aldolase B then undergoes phosphorylation to glyceraldehyde 3-phosphate. Increased concentrations of DHAP and glyceraldehyde 3-phosphate in the liver drive the gluconeogenic pathway toward glucose and subsequent glycogen synthesis. It appears that fructose is a better substrate for glycogen synthesis than glucose and that glycogen replenishment takes precedence over triglyceride formation. Once liver glycogen is replenished, the intermediates of fructose metabolism are primarily directed toward triglyceride synthesis.

Synthesis of triglyceride from DHAP and glyceraldehyde 3-phosphate

Carbons from dietary fructose are found in both the free fatty acid and glycerol moieties of plasma triglycerides. High fructose consumption can lead to excess pyruvate production, causing a buildup of Krebs cycle intermediates. Accumulated citrate can be transported from the mitochondria into the cytosol of hepatocytes, converted to acetyl CoA by citrate lyase and directed toward fatty acid synthesis. In addition, DHAP can be converted to glycerol 3-phosphate, providing the glycerol backbone for the triglyceride molecule. Triglycerides are incorporated into very-low-density lipoproteins (VLDL), which are released from the liver destined toward peripheral tissues for storage in both fat and muscle cells.

Potential health effects

In 2022, the European Food Safety Authority stated that there is research evidence that fructose and other added free sugars may be associated with increased risk of several chronic diseases: the risk is moderate for obesity and dyslipidemia (more than 50%), and low for non-alcoholic fatty liver disease, type 2 diabetes (from 15% to 50%) and hypertension. EFSA further stated that clinical research did "not support a positive relationship between the intake of dietary sugars, in isocaloric exchange with other macronutrients, and any of the chronic metabolic diseases or pregnancy-related endpoints assessed" but advised "the intake of added and free sugars should be as low as possible in the context of a nutritionally adequate diet."

Obesity

Excessive consumption of sugars, including fructose, contributes to insulin resistance, obesity, elevated LDL cholesterol and triglycerides, leading to metabolic syndrome. The European Food Safety Authority (EFSA) stated in 2011 that fructose may be preferable over sucrose and glucose in sugar-sweetened foods and beverages because of its lower effect on postprandial blood sugar levels, while also noting the potential downside that "high intakes of fructose may lead to metabolic complications such as dyslipidaemia, insulin resistance, and increased visceral adiposity". The UK's Scientific Advisory Committee on Nutrition in 2015 disputed the claims of fructose causing metabolic disorders, stating that "there is insufficient evidence to demonstrate that fructose intake, at levels consumed in the normal UK diet, leads to adverse health outcomes independent of any effects related to its presence as a component of total and free sugars."

Cardiometabolic diseases

When fructose is consumed in excess as a sweetening agent in foods or beverages, it may be associated with increased risk of obesity, diabetes, and cardiovascular disorders that are part of metabolic syndrome.

Compared with sucrose

Fructose was found to increase triglycerides in type-2 but not type-1 diabetes, and moderate use of it has previously been considered acceptable as a sweetener for diabetics, possibly because it does not trigger the production of insulin by pancreatic β cells. For a 50 gram reference amount, fructose has a glycemic index of 23, compared with 100 for glucose and 60 for sucrose. Fructose is also 73% sweeter than sucrose at room temperature, allowing diabetics to use less of it per serving. Fructose consumed before a meal may reduce the glycemic response of the meal. Fructose-sweetened food and beverage products cause less of a rise in blood glucose levels than do those manufactured with either sucrose or glucose.