Fructose is a natural sugar, a monosaccharide found naturally in fruit, vegetables, honey and is also found in breast milk.
It has 4 kcal per gram and is used as a sugar substitute in the food industry.

It is to be consumed in moderation because the chronic intake of fructose has important contraindications.

Fructose is another component with a friendly and inviting name, but whose excessive consumption can create health risks. This ingredient is often included in sweets, food drinks etc. with the aim of increasing the sweet taste and we find it in 

• high-fructose corn syrup 
• inverted sugar syrup (contains 36% fructose) 
• glucose-fructose syrup 
• fructose syrup 

 and also pure.

Origin. Extracted primarily from plant sources such as fruit, honey, and sugar cane or sugar beet plants.

Functions of Raw Materials.

Fruit and Honey. Provide natural fructose, known for its high sweetening power and being sweeter than glucose.

A list of fruits that are particularly high in fructose:

• Apples: Especially the sweeter varieties.
• Pears: They can sometimes even have a higher fructose content than apples.
• Watermelon: Contains a significant amount of fructose, especially given the volume that people often consume.
• Grapes: Especially the sweeter varieties like Concord and Thompson seedless.
• Mangoes: One of the sweeter tropical fruits.
• Papayas: Another tropical fruit with a high fructose content.
• Pineapples: Especially when fully ripe.
• Lychees: These small fruits pack a lot of sweetness.
• Honeydew Melon: Contains a significant amount of fructose.
• Agave Nectar: While not a fruit, it's worth noting that this sweetener, derived from the agave plant, is extremely high in fructose.

It's important to note that while these fruits are high in fructose, they also offer a range of essential nutrients, including vitamins, minerals, and fiber. 

Consuming them in moderation as part of a balanced diet can offer health benefits. However, individuals with conditions like fructose malabsorption or hereditary fructose intolerance should be cautious and consult with a healthcare professional about their fruit intake.

Industrial Production Process

The industrial production of pure fructose, as opposed to high fructose corn syrup (HFCS) production, follows a specific process aimed at obtaining high-purity crystalline fructose, used in various sectors for its superior sweetening properties and low glycemic index. Here is an overview of the process:

• Extraction from Sucrose. Fructose is often industrially produced through the enzymatic hydrolysis of sucrose, a sugar composed of glucose and fructose. This process utilizes the enzyme invertase, which cleaves sucrose into an equimolar mixture of glucose and fructose.
• Purification. The liquid mixture of glucose and fructose undergoes purification processes to remove impurities and separate the two monosaccharides. Ion exchange chromatography is commonly used to separate fructose from glucose, thanks to their different affinity for the exchange resin.
• Crystallization. The purified fructose is concentrated and subjected to crystallization. This process may require controlled temperature and concentration conditions to promote the formation of fructose crystals.
• Drying. The fructose crystals are then dried to remove residual moisture, yielding pure crystalline fructose. Drying can be carried out using fluid bed dryers or spray dryers.
• Quality Control. The crystalline fructose undergoes rigorous quality control checks to verify purity, the absence of contaminants, and compliance with food specifications. This includes chromatographic analyses to determine the purity of fructose and microbiological 

Form and Color

Fructose appears as a white crystal or fine powder highly soluble in water.

Studies

Added sugar is a risk factor for obesity and metabolic diseases including type 2 diabetes mellitus, cardiovascular disease, and nonalcoholic hepatic steatosis (1).

Excessive fructose consumption has been linked, at least partially, to increased adiposity and metabolic disturbances compared with other sugars that appear to be particularly important during critical periods of childhood growth and development (2).

Fructose induces oxidative stress through several mechanisms. First, because fructose is structurally different from glucose, it may promote more hepatocellular damage. Second, an overload of Fructose induces a glycation product that may interact with some proteins unfavorably.  Third, an accelerated glycolytic process with fructose increases the formation of molecules such as Methylglyoxal, an agent that leads to cellular stress and altered insulin signaling (3).

There is also evidence between consumption of refined dietary sugars (fructose and glucose) and retinal diseases (4).

A recent study attributes excessive fructose intake to the progression of diabetic kidney disease (5).

As reported in a safety study of high-fructose corn syrup and fructose used as sweeteners, both showed an effect cytotoxic effect at HepG2 and human lymphocytes at higher concentrations.Both sweeteners increased the frequencies of CAs and SCEs at higher concentrations.HFCS caused DNA damage at 10% -30% concentrations.HFCS (15% and 20%) and FR (250, 1000, and 2000 μg/mL) induced MN frequency (6).

Cosmetics

Flavoring agent. The purpose of this ingredient is to modify the solution to add flavour. Natural flavouring extracts are rather expensive, so the cosmetic and pharmaceutical industries resort to synthesised substances that have sensory characteristics mostly similar to natural flavourings or are naturally equivalent. This ingredient is isolated through chemical processes or is synthesised from chemicals.

Skin conditioning agent -  Humectant. Humectants are hygroscopic substances used to minimise water loss in the skin and to prevent it from drying out by facilitating faster and greater absorption of water into the stratum corneum of the epidermis. The epidermis is the most superficial of the three layers that make up the human skin (epidermis, dermis and hypodermis) and is the layer that maintains hydration in all three layers. In turn, the epidermis is composed of five layers: corneum, the most superficial, lucidum, granulosum, spinosum and basale. Humectants have the ability to retain in the stratum corneum the water they attract from the air and have the function of moisturising the skin. It is better to use them before emollients that are oil-based.

Fructose studies

References___________________________________________________________________

(1) Welsh, J.A.; Sharma, A.; Cunningham, S.A.; Vos, M.B. Consumption of added sugars and indicators of cardiovascular disease risk among US adolescents. Circulation. 2011 Jan 25;123(3):249-57. doi: 10.1161/CIRCULATIONAHA.110.972166. 

Abstract. Background: Whereas increased carbohydrate and sugar consumption has been associated with higher cardiovascular disease risk among adults, little is known about the impact of high consumption of added sugars (caloric sweeteners) among US adolescents....Conclusion: Consumption of added sugars among US adolescents is positively associated with multiple measures known to increase cardiovascular disease risk.

(2) Goran, M.I.; Dumke, K.; Bouret, S.G.; Kayser, B.; Walker, R.W.; Blumberg, B. The obesogenic effect of high fructose exposure during early development. Nat Rev Endocrinol. 2013 Aug;9(8):494-500. doi: 10.1038/nrendo.2013.108. 

Abstract. Obesogens are compounds that disrupt the function and development of adipose tissue or the normal metabolism of lipids, leading to an increased risk of obesity and associated diseases. Evidence for the adverse effects of industrial and agricultural obesogens, such as tributyltin, bisphenol A and other organic pollutants is well-established. Current evidence suggests that high maternal consumption of fat promotes obesity and increased metabolic risk in offspring, but less is known about the effects of other potential nutrient obesogens. Widespread increase in dietary fructose consumption over the past 30 years is associated with chronic metabolic and endocrine disorders and alterations in feeding behaviour that promote obesity. In this Perspectives, we examine the evidence linking high intakes of fructose with altered metabolism and early obesity. We review the evidence suggesting that high fructose exposure during critical periods of development of the fetus, neonate and infant can act as an obesogen by affecting lifelong neuroendocrine function, appetite control, feeding behaviour, adipogenesis, fat distribution and metabolic systems. These changes ultimately favour the long-term development of obesity and associated metabolic risk.

Johnson RJ, Sánchez-Lozada LG, Lanaspa MA. The fructose survival hypothesis as a mechanism for unifying the various obesity hypotheses. Obesity (Silver Spring). 2023 Oct 17. doi: 10.1002/oby.23920. 

(3) Prasanthi Jegatheesan and Jean-Pascal De Bandt. Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism  Nutrients 2017, 9(3), 230; doi:10.3390/nu9030230

Abstract. Among various factors, such as an unhealthy diet or a sedentarity lifestyle, excessive fructose consumption is known to favor nonalcoholic fatty liver disease (NAFLD), as fructose is both a substrate and an inducer of hepatic de novo lipogenesis. The present review presents some well-established mechanisms and new clues to better understand the pathophysiology of fructose-induced NAFLD. Beyond its lipogenic effect, fructose intake is also at the onset of hepatic inflammation and cellular stress, such as oxidative and endoplasmic stress, that are key factors contributing to the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Beyond its hepatic effects, this carbohydrate may exert direct and indirect effects at the peripheral level. Excessive fructose consumption is associated, for example, with the release by the liver of several key mediators leading to alterations in the communication between the liver and the gut, muscles, and adipose tissue and to disease aggravation. These multifaceted aspects of fructose properties are in part specific to fructose, but are also shared in part with sucrose and glucose present in energy- dense beverages and foods. All these aspects must be taken into account in the development of new therapeutic strategies and thereby to better prevent NAFLD.

(4) Kearney FM, Fagan XJ, Al-Qureshi S. Review of the role of refined dietary sugars (fructose and glucose) in the genesis of retinal disease. Clin Exp Ophthalmol. 2014 Aug;42(6):564-73. doi: 10.1111/ceo.12290. 

(5) Tsuruta H, Yasuda-Yamahara M, Yoshibayashi M, Kuwagata S, Yamahara K, Tanaka-Sasaki Y, Chin-Kanasaki M, Matsumoto S, Ema M, Kume S. Fructose overconsumption accelerates renal dysfunction with aberrant glomerular endothelial-mesangial cell interactions in db/db mice. Biochim Biophys Acta Mol Basis Dis. 2024 Feb 13;1870(4):167074. doi: 10.1016/j.bbadis.2024.167074. 

Abstract. For the advancement of DKD treatment, identifying unrecognized residual risk factors is essential. We explored the impact of obesity diversity derived from different carbohydrate qualities, with an emphasis on the increasing trend of excessive fructose consumption and its effect on DKD progression. In this study, we utilized db/db mice to establish a novel diabetic model characterized by fructose overconsumption, aiming to uncover the underlying mechanisms of renal damage. Compared to the control diet group, the fructose-fed db/db mice exhibited more pronounced obesity yet demonstrated milder glucose intolerance. Plasma cystatin C levels were elevated in the fructose model compared to the control, and this elevation was accompanied by enhanced glomerular sclerosis, even though albuminuria levels and tubular lesions were comparable. Single-cell RNA sequencing of the whole kidney highlighted an increase in Lrg1 in glomerular endothelial cells (GECs) in the fructose model, which appeared to drive mesangial fibrosis through enhanced TGF-β1 signaling. Our findings suggest that excessive fructose intake exacerbates diabetic kidney disease progression, mediated by aberrant Lrg1-driven crosstalk between GECs and mesangial cells.

(6) Bülbül SN, Mamur S, Yuzbasioglu D, Unal F. Safety Assessment of High Fructose Corn Syrup and Fructose Used as Sweeteners in Foods. Toxicol Mech Methods. 2024 Feb 12:1-19. doi: 10.1080/15376516.2024.2318570. 

Abstract. High Fructose Corn Syrup (HFCS) and Fructose (FR) are widely used sweeteners in many foods and beverages. This study aimed at investigating the cytotoxic effects of HFCS (5%-30%) and FR (62.5-2000 μg/mL) using MTT assay in Human Hepatocellular Carcinoma (HepG2) cells, and genotoxic effects of using Chromosome Aberrations (CAs), Sister Chromatid Exchanges (SCEs), Micronuclei (MN) and comet assays in human lymphocytes. HFCS significantly reduced the cell viability in HepG2 cells at between 7.5% and 30% for 24 and 48 hours. 30% HFCS caused a very significant toxic effect. FR had a cytotoxic effect in HepG2 cells at all treatments. However, as fructose concentration decreased, the cell viability decreased. HFCS (10%-20%) and FR (250-2000 μg/mL) decreased the mitotic index at higher concentrations. IC50 value was found to be a 15% for 48 h. IC50 value of FR was detected as 62.5 μg/mL for 24 h and 48 h. HFCS significantly increased CAs frequency at 15% and 20%. FR significantly increased the frequency of CAs at 250, 1000, and 2000 μg/mL for 48 h. Both sweeteners increased the frequency of SCEs at all concentrations. HFCS (15% and 20%) and FR (250, 1000, and 2000 μg/mL) induced MN frequency at higher concentrations. HFCS caused DNA damage in comet assay at 10% -30%. FR increased tail intensity and moment at 125-2000 μg/mL and tail length at 62.5, 250 and 500 μg/mL. Therefore, HFCS and FR are clearly seen to be cytotoxic and genotoxic, especially at higher concentrations.