High fructose corn syrup (HFCS) is a liquid sweetener made by enzymatically transforming corn starch into glucose, followed by converting a portion of this glucose into fructose. HFCS is widely used in the food industry for its sweetening properties, its ability to extend the shelf life of products, and its relatively low cost.

Composition. HFCS comes in different concentrations, the most common being HFCS-42 (42% fructose) and HFCS-55 (55% fructose), primarily used in soft drinks. The exact composition can vary depending on the specific application.

Sweetening Properties. HFCS has a sweetening power similar to or slightly higher than sucrose (table sugar), making it an attractive substitute in many food products and beverages.

Preservation. HFCS helps to retain moisture in baked goods, improving texture and prolonging freshness. This makes it particularly useful in products like bread, cakes, and cookies.

Cost and Efficiency. The production of HFCS is economically advantageous compared to other sweeteners, due to the abundance and low cost of corn starch. This has led to its widespread use in the food industry.

Industrial Production Process

• Milling. Corn kernels are cleaned and then milled to separate the corn germ (which contains oil) from the endosperm (which contains starch). The milling process involves soaking the corn and then grinding it to produce a slurry.
• Starch Extraction. The slurry is processed to separate the starch from the protein (gluten) and fiber. Centrifugation and hydrocyclones are commonly used for this separation. The result is a pure starch slurry.
• Enzymatic Liquefaction. The starch slurry is treated with alpha-amylase enzymes and heated under specific conditions (usually around 85-105°C) to break down the starch into shorter chains of polysaccharides (oligosaccharides). This process, known as liquefaction, reduces the viscosity of the slurry and prepares it for further hydrolysis.
• Enzymatic Saccharification. The oligosaccharides are further broken down into simpler sugars, primarily glucose, using another enzyme, glucoamylase. This step, called saccharification, operates at lower temperatures (around 60°C) and might include pH adjustments to optimize enzyme activity.
• Glucose Isomerization. The glucose syrup is then converted into fructose using an enzyme called glucose isomerase. This process converts some of the glucose into fructose, resulting in a mixture known as high fructose corn syrup. The initial HFCS produced typically contains about 42% fructose (HFCS-42), with the rest being glucose and other sugars.
• Chromatographic Separation. To increase the fructose content, the HFCS-42 can undergo chromatographic separation, a process that selectively removes glucose, increasing the fructose concentration to 55% or higher (HFCS-55 or higher), which is closer in sweetness to sucrose and preferred for soft drinks and other sweetened beverages.
• Purification. The HFCS is purified through carbon and ion-exchange filters to remove impurities and unwanted tastes or odors.
• Concentration. The syrup may be concentrated under vacuum to achieve the desired solids content, enhancing its sweetness and stability.
• Quality Control. Throughout the production process, rigorous quality control measures are in place to ensure the purity, safety, and consistency of the HFCS. This includes monitoring the enzymatic reactions, verifying the composition of the syrup, and testing for contaminants.

Chemical and Enzymatic Reactions

Liquefaction: Starch (C₆H₁₀O₅)n + H₂O → Oligosaccharides

Saccharification: Oligosaccharides + H₂O → Glucose (C₆H₁₂O₆)

Isomerization: Glucose (C₆H₁₂O₆) → Fructose (C₆H₁₂O6)

The enzymes play crucial roles in these reactions, acting as catalysts to convert starch into glucose and then glucose into fructose without changing the enzymes themselves.

Safety

Impact on Metabolism. The high fructose content in HFCS can adversely affect metabolism, contributing to weight gain, insulin resistance, and fat accumulation in the liver. These effects have been linked to an increased risk of obesity, type 2 diabetes, and cardiovascular diseases. The widespread use of HFCS has raised public health concerns, with studies linking excessive consumption to various health issues. This has sparked debate over the need to limit its use in food products.

Studies

Dietary fructose intake increased significantly from 1970 to 2000 and during this period there was a 25% increase worldwide in the so-called "added sugars" (1). This is because fructose is sweeter than glucose and sucrose, while in beverages it serves to give the optimal sweet taste.

The increased consumption of fructose has increased, in parallel, with the spread of obesity, which suggests a relationship (2) and furthermore, in this article (3), fructose in the diet is indicated as a potential risk factor for cardiovascular diseases.

In the study conducted by Aeberli et al. (4), dietary factors, in particular fructose, were examined in relation to the body mass index, waist-hip ratio, plasma lipid profile, and LDL particle size in 74 Swiss schoolchildren aged between 6 and 14 years. In this study the plasma triglycerides were higher, HDL cholesterol concentrations were lower, and the size of the lipoproteins (LDL) of the particles were smaller in overweight children than in normal weight children. The fatter children had smaller sizes of LDL particles, and, even after being checked for adiposity, the fructose intake diet was the only dietary factor related to LDL particle size. In this study, fructose was free, and not sucrose, which was shown to be related to the effect of LDL particle size (5). Studies conducted on rodents, dogs and non-human primates that have a diet high in fructose or sucrose consistently demonstrate hyperlipidemia (6). The current report Aeberli and others, suggests that the higher intake of fructose by school-age children can have negative effects, with a future risk of cardiovascular disease, reducing the size of LDL particles.

References_____________________________________________________________________

(1) Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev. 2005 May;63(5):133-57. doi: 10.1301/nr.2005.may.133-157.

Abstract. Fructose intake and the prevalence of obesity have both increased over the past two to three decades. Compared with glucose, the hepatic metabolism of fructose favors lipogenesis, which may contribute to hyperlipidemia and obesity. Fructose does not increase insulin and leptin or suppress ghrelin, which suggests an endocrine mechanism by which it induces a positive energy balance. This review examines the available data on the effects of dietary fructose on energy homeostasis and lipid/carbohydrate metabolism. Recent publications, studies in human subjects, and areas in which additional research is needed are emphasized.

(2) Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr. 2004 Apr;79(4):537-43. doi: 10.1093/ajcn/79.4.537. Erratum in: Am J Clin Nutr. 2004 Oct;80(4):1090. 

Abstract. Obesity is a major epidemic, but its causes are still unclear. In this article, we investigate the relation between the intake of high-fructose corn syrup (HFCS) and the development of obesity. We analyzed food consumption patterns by using US Department of Agriculture food consumption tables from 1967 to 2000. The consumption of HFCS increased > 1000% between 1970 and 1990, far exceeding the changes in intake of any other food or food group. HFCS now represents > 40% of caloric sweeteners added to foods and beverages and is the sole caloric sweetener in soft drinks in the United States. Our most conservative estimate of the consumption of HFCS indicates a daily average of 132 kcal for all Americans aged > or = 2 y, and the top 20% of consumers of caloric sweeteners ingest 316 kcal from HFCS/d. The increased use of HFCS in the United States mirrors the rapid increase in obesity. The digestion, absorption, and metabolism of fructose differ from those of glucose. Hepatic metabolism of fructose favors de novo lipogenesis. In addition, unlike glucose, fructose does not stimulate insulin secretion or enhance leptin production. Because insulin and leptin act as key afferent signals in the regulation of food intake and body weight, this suggests that dietary fructose may contribute to increased energy intake and weight gain. Furthermore, calorically sweetened beverages may enhance caloric overconsumption. Thus, the increase in consumption of HFCS has a temporal relation to the epidemic of obesity, and the overconsumption of HFCS in calorically sweetened beverages may play a role in the epidemic of obesity.

(3) Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol. 2006 Mar;290(3):F625-31. doi: 10.1152/ajprenal.00140.2005. Epub 2005 Oct 18. PMID: 16234313.

Abstract. The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.

(4) Aeberli I, Zimmermann MB, Molinari L, Lehmann R, l'Allemand D, Spinas GA, Berneis K. Fructose intake is a predictor of LDL particle size in overweight schoolchildren. Am J Clin Nutr. 2007 Oct;86(4):1174-8. doi: 10.1093/ajcn/86.4.1174. 

Abstract. Background: High amounts of dietary fructose may contribute to dyslipidemia in adults, but there are few data in children. Childhood adiposity is associated with smaller LDL particle size, but the dietary predictors of LDL size in overweight children have not been studied. Objectives: We aimed to determine whether LDL particle size is associated with dietary factors and specifically with fructose intake in normal-weight and overweight children.....Conclusions: In school-age children, greater total and central adiposity are associated with smaller LDL particle size and lower HDL cholesterol. Overweight children consume more fructose from sweets and sweetened drinks than do normal-weight children, and higher fructose intake predicts smaller LDL particle size.

(5) Bray GA. How bad is fructose? Am J Clin Nutr. 2007 Oct;86(4):895-6. doi: 10.1093/ajcn/86.4.895. PMID: 17921361.

(6) Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev. 2005 May;63(5):133-57. doi: 10.1301/nr.2005.may.133-157. PMID: 15971409.

Abstract. Fructose intake and the prevalence of obesity have both increased over the past two to three decades. Compared with glucose, the hepatic metabolism of fructose favors lipogenesis, which may contribute to hyperlipidemia and obesity. Fructose does not increase insulin and leptin or suppress ghrelin, which suggests an endocrine mechanism by which it induces a positive energy balance. This review examines the available data on the effects of dietary fructose on energy homeostasis and lipid/carbohydrate metabolism. Recent publications, studies in human subjects, and areas in which additional research is needed are emphasized.