Glucose-fructose syrup and fructose in nutrition and food industry

Added sugars consumption — comprised largely of glucose and fructose principally from sucrose and high fructose corn syrup (HFCS) — is declining in developed countries, but increasing in developing countries (Marriott B.P. et al., 2014). The latter researchers estimated the U.S. consumption of fructose at 9.1% and 14.5% of energy intake for the population mean and 95th percentile, respectively. Although there was a transient increase in fructose consumption with the introduction of HFCS in 1970, fructose consumption has remained remarkably constant at 39±4 g/day for nearly a century. The current interest in fructose fructose is associated with the widespread use of HFCS in the production of beverages, confectionery, canned goods and ice cream (Nechaev A.P., 2008; Lukin N.D., 2011; White J.S., 2013). HFCS is a liquid sweetener with about the same sweetness as sucrose, but a lower price; it is obtained from corn starch in the U.S., but can be produced from other starches like potato, wheat, tapioca and rice. The wide introduction of HFCS in the food industry of the U.S. and other countries began in the late 1960s, which was accompanied by the partial replacement of conventional sugar (sucrose). HFCS-42 type contains 42% of fructose and HFCS-55 contains 55% (Sun S.Z. et al., 2011; Golyibin V.A., Efremov A.A., 2013; Sapronov A.R. et al., 2013; White J.S., 2013).

Sugary products manufactured from starch or flour by acid and/or enzymatic hydrolysis have been known in Russia as starch hydrolyzate, glucose syrup, caramelic syrup (patoka), flour hydrolyzate or saccharified flour; since the 1980s, high fructose syrup is also known by this name in Russia (Voloshanenko G.P., 1985; Antonova Zh.V. et al., 1994; GOST, 2016). HFCS is obtained from glucose by treatment with the enzyme isomerase. At present, various enzymes of bacterial or fungal origin are used (Guzmán-Maldonado H. et al., 1995; Dziedzic S.Z., Kearsley M.W., 1984).

Fructose is found in many fruits; it differs from sucrose and glucose by a low glycemic index and a more sweet taste, which, in itself, is an advantage for people with obesity and diabetes mellitus. Absorption of fructose in the intestine is limited, decreases with age and is stimulated by glucose (Kolderup A., Svihus B., 2015; Malik V.S., Hu F.B., 2015; Tappy L. et al., 2010). Malabsorption of fructose can occur when it predominates over glucose in the diet; however, there is generally sufficient glucose in the diet to facilitate quantitative fructose absorption. Different types of carbohydrate intolerance, including fructose malabsorption, are relatively common in individuals with symptoms of «irritable bowel» (Berni Canani R. et al., 2016).

Much of the fructose is processed in the liver; unlike glucose, its metabolism is independent of insulin. Concern was expressed about the ability of fructose, consumed in large quantities, to enhance the synthesis of lipids in the liver and to promote insulin resistance in diabetes mellitus. Long-term use of fructose led to an increase in body weight and insulin resistance in rodents (Tappy L., Le K.A., 2010; Softic S. et al., 2016). According to the review S.W. Rizkalla (2010), there is no convincing evidence for insulin resistance in humans under the impact of fructose. There may be a slight increase of the insulin resistance in the liver, but not at the level of the whole organism (Tappy L., Le K.A., 2010). The intake of large doses of fructose was accompanied by a decrease in the blood levels of insulin and leptin (the hormone that suppresses the appetite). In contrast, the administration of sucrose increased the level of insulin and leptin, which led to a decrease in appetite. It was suggested that a less effective suppression of hunger under the impact of fructose could contribute to overeating (Lakhan S.E., Kirchgessner A., 2013). However, there was no difference between HFCS and sucrose in this regard. At the same time, it was reported that consumption of fructose before meals in drinks or sweet dishes reduces the appetite (Rizkalla S.W., 2010). The doses of fructose in experiments were much higher than the usual level of its consumption (Harchenko T.A., 2012; Macdonald I.A., 2016). In many studies, a mixture of sugars was used. In the absence of a control group with glucose intake, the observed effects could be caused not only by fructose, but also by other sugars. Care must be taken when interpreting the results of studies with high doses of fructose: many food substances exhibit toxic properties with excessive consumption. Based on the review of the literature, it was concluded that fructose is a valuable product; and there are no grounds for limiting its consumption (Glinsmann W.H., Bowman B.A., 1993).

There were suggestions of a causal relationship between the increase in HFCS consumption and the prevalence of obesity (metabolic syndrome) in developed countries. This assumption does not take into account that the fructose/glucose ratio in sucrose and HFCS is approximately the same (Sun S.Z. et al., 2011; White J.S., 2013). There are no reliable data in support of the supposition that HFCS affects the body weight more than other sources of sugar (Tappy L. et al., 2010). Nevertheless, fructose and HFCS continue to be accused also from the sugar-producing regions; fructose was even named toxin (Johnson R.J. et al., 2010). The same authors with references to experiments with high doses reported an allegedly harmful effect of fructose on renal function. An association between the consumption of fructose and arterial hypertension in humans was reported, although in fact only a temporary increase in blood pressure after taking large doses of fructose e.g. 200 g/day for 2 weeks had taken place. An increase in blood pressure after a single intake of 60 g of fructose was reported, in the absence of a similar effect from glucose (Johnson R.J. et al., 2010). It would be interesting to verify these data in an independent experiment. Fructose was even compared with ethyl alcohol (Lustig R.H., 2010), which is hardly adequate in view of the differences in dosages and purposes of taking these substances. It is important to emphasize that dietary sources of fructose, as a rule, contain 3–5 times as much glucose (White J.S., 2013). One of the main sources of fructose is sucrose, a molecule which is split in the gastrointestinal tract to fructose and glucose. In the diet, fructose rarely prevails over other sugars (Sun S.Z. et al., 2011). In this connection, the results of experiments with pure fructose are difficult to transfer to the human nutrition. Moreover, about half of the consumed fructose is processed by the liver into glucose (Tappy L., Le K.A., 2010). In some studies, the effects of taking large doses of pure fructose and glucose were compared (White J.S., 2013). Obviously, the results of such studies are of little use for assessing risks in humans, where lower amounts of fructose and glucose are consumed, and they are consumed together.

In meta-analyses, the data on fructose consumption were compared with other carbohydrates e.g. sucrose, starch and HFCS. Differences in weight gain, arterial pressure and uric acid levels were not detected, either among healthy individuals or in patients with diabetes mellitus (Cozma A.I. et al., 2012; Sievenpiper J.L. et al., 2012; Wang D.D. et al., 2012; Ha V. et al., 2012). In diabetes, the intake of fructose did not increase insulin resistance (Cozma A.I. et al., 2012). Effects of moderate doses of fructose on blood lipid levels and body weight were not detected in persons with normal weight or obesity (Dolan L.C. et al., 2010). When comparing the levels of insulin, leptin, the «hunger hormone» ghrelin, triglycerides, uric acid, the sensations of hunger and satiety in subjects taking HFCS and sucrose, there were no significant differences (Melanson K.J. et al, 2007; Soenen S., Westerterp-Plantenga M.S., 2007; Stanhope K.L. et al., 2008). In a cohort of 17,700 individuals with biochemical signs of the metabolic syndrome, the intake of fructose and other sugars was compared; no statistically significant differences in the levels of triglycerides, cholesterol, glycated hemoglobin, uric acid, arterial pressure and body mass index were found (Sun S.Z. et al., 2011). The review by L. Tappy, B. Mittendorfer (2012) concluded that epidemiological data confirm the relationship between sugar consumption and excess weight, but do not support the hypothesis of the special role of fructose in comparison with other sugars. A moderate intake of fructose (up to 50 g/day) does not impair the metabolism of lipids and glucose, and the doses up to 100 g/day do not affect the body weight (Rizkalla S.W., 2010). Convincing data in favor of health risks from moderate fructose consumption are unknown. According to the review by Tappy L., Le K.A. (2010), a very high level of fructose intake can adversely affect metabolism, but the role of moderate consumption — typical in the human diet — as a cause of the increasing incidence of metabolic syndrome is not proven.

It can be concluded from the literature that fructose has no deleterious effects at the usual level of consumption, but can cause undesirable effects when taken in high doses. The same, obviously, can be said about many food products and their ingredients. At the usual level of consumption, fructose does not differ from other sugars in action on the body weight, blood pressure, blood lipids, uric acid, etc. Consumption of fructose is accompanied by a lower rise in blood sugar level than that of both sucrose and glucose (White J.S., 2013). Unrealistically high doses of fructose taken in by experimental subjects can lead to accumulation of lipids in the liver and skeletal muscles; however, other carbohydrates may possess similar effects. It is possible that the lipid accumulation is a consequence of the excess calorie content of food, rather than the specific action of fructose (Macdonald I.A., 2016). The available data do not give grounds for believing that a moderate intake of fructose (50–60 g/day) affects body weight, the risk of atherosclerosis and diabetes mellitus more than other sugars (Malik V.S., Hu F.B., 2015; Khan T.A., Sievenpiper J.L., 2016).

The study of impurities in food products using modern methods, such as chromatography and spectrometry, is of importance. It has been reported, however, that in gas chromatography with mass spectrometry, an acidic medium and an elevated temperature can cause the decomposition of sugars with the appearance of impurities that were originally absent in the sample (White J.S. et al., 2015). Admixtures of alpha-dicarbonyl compounds including methylglyoxal and glyoxal have been reported, while their concentration largely depended on the manufacturer of HFCS (Gensberger S. et al., 2012, 2013). The dicarbonyls are decomposition products from the Maillard browning reaction, formed by heating of sugars in the presence of amino acids. Note that these substances, at a lower concentration, are present in other foods, and are also synthesized in the body (COT, 2009; Shangari N. et al., 2003; White J.S., 2009). The data on the cytotoxic, mutagenic and pro-oxidative effects of dicarbonyl compounds and the products of their interaction with proteins (advanced glycation endproducts) seem to be unconvincing (White J.S., 2009) and require studies at concentrations corresponding to those in HFCS and in vivo. The presence of another product of monosaccharide decomposition 5-hydroxymethyl-2-furfural in HFCS was reported (de Andrade J.K. et al., 2017), the latter substance being also formed in baked goods and caramels. In the past, trace amounts of mercury were reported in HFCS; in the U.S., this trace impurity was eliminated by changed technology (Dufault R., et al., 2009). In conclusion, the problem of impurities should not be exaggerated: HFCS is sufficiently well studied and is considered a safe product (White J.S. et al., 2015).

List of used literature

• Antonova Zh.V., Virovets O.A., Gapparov M.M. (1994) Vliyanie razlichnyih vidov suhokrahmalnoy patoki na tempyi utilizatsii glyukozyi v lipidnyie, uglevodnyie i belkovyie komponentyi pecheni. Vopr. med. him., 5: 34–36.
• Berni Canani R., Pezzella V., Amoroso A. et al. (2016) Diagnosing and treating intolerance to carbohydrates in children. Nutrients, 8(3): 157.
• COT (2009) Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Statement on Methylglyoxal 2009/04.
• Cozma A.I., Sievenpiper J.L., de Souza R.J. et al. (2012) Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials. Diabetes Care, 35: 1611–1620.
• de Andrade J.K., de Andrade C.K., Komatsu E. et al. (2017) A validated fast difference spectrophotometric method for 5-hydroxymethyl-2-furfural (HMF) determination in corn syrups. Food Chem., 228: 197–203.
• Dolan L.C., Potter S.M., Burdock G.A. (2010) Evidence-based review on the effect of normal dietary consumption of fructose on blood lipids and body weight of overweight and obese individuals. Crit. Rev. Food Sci. Nutr., 50: 889–918.
• Dufault R., Schnoll R., Lukiw W.J. et al. (2009) Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children. Behav. Brain Funct., 5: 44.
• Dziedzic S.Z., Kearsley M.W. (1984) Glucose syrups. Elsevier, London.
• Gensberger S., Glomb M.A., Pischetsrieder M. (2013) Analysis of sugar degradation products with α-dicarbonyl structure in carbonated soft drinks by UHPLC-DAD-MS/MS. J. Agric. Food Chem., 61(43): 10238–10245.
• Gensberger S., Mittelmaier S., Glomb M.A., Pischetsrieder M. (2012) Identification and quantification of six major α-dicarbonyl process contaminants in high-fructose corn syrup. Anal. Bioanal. Chem., 403(10): 2923–2931.
• Glinsmann W.H., Bowman B.A. (1993) The public health significance of dietary fructose. Am. J. Clin. Nutr., 58(5 Suppl.): 820S–823S.
• Golyibin V.A., Efremov A.A. (2013) Tehnologiya krahmala, krahmaloproduktov i glyukozno-fruktoznyih siropov. VGUIT, Voronezh.
• GOST (2016) GOST 33917-2016. Patoka krahmalnaya. Obschie tehnicheskie usloviya (http://docs.cntd.ru/document/1200142451).
• Guzmán-Maldonado H., Paredes-López O. (1995) Amylolytic enzymes and products derived from starch: a review. Crit. Rev. Food Sci. Nutr., 35: 373–403.
• Ha V., Sievenpiper J.L., de Souza R.J. et al. (2012) Effect of fructose on blood pressure: a systematic review and meta-analysis of controlled feeding trials. Hypertension, 59: 787–795.
• Harchenko T.A. (2012) Polneyut li ot sahara? Ukr. med. chasopis, 21 fevralya  (http://www.umj.com.ua/article/27345/polneyut-li-ot-saxara).
• Johnson R.J., Sanchez-Lozada L.G., Nakagawa T. (2010) The effect of fructose on renal biology and disease. J. Am. Soc. Nephrol., 21: 2036–2039.
• Khan T.A., Sievenpiper J.L. (2016) Controversies about sugars: results from systematic reviews and meta-analyses on obesity, cardiometabolic disease and diabetes. Eur. J. Nutr., 55 (Suppl. 2): 25–43.
• Kolderup A., Svihus B. (2015) Fructose metabolism and relation to atherosclerosis, type 2 diabetes, and obesity. J. Nutr. Metab., 2015: 823081.
• Lakhan S.E., Kirchgessner A. (2013) The emerging role of dietary fructose in obesity and cognitive decline. Nutr. J., 12: 114.
• Lukin N.D. (2011) K voprosu importozamescheniya sahara otechestvennyimi krahmaloproduktami. V kn: Trudyi Mezhdunar. nauchno-prakt. konf. «Krahmal i krahmaloproduktyi, sostoyanie i perspektivyi razvitiya». Moskva, s. 70–81.
• Lustig R.H. (2010) Fructose: metabolic, hedonic, and societal parallels with ethanol. J. Am. Diet. Assoc., 110: 1307–1321.
• Macdonald I.A. (2016) A review of recent evidence relating to sugars, insulin resistance and diabetes. Eur. J. Nutr., 55 (Suppl. 2): S17–S23.
• Malik V.S., Hu F.B. (2015) Fructose and cardiometabolic health: What the evidence from sugar-sweetened beverages tells us. J. Am. Coll. Cardiol., 66: 1615–1624.
• Marriott B.P., Fink C.J., Krakower T. (2014) Worldwide Consumption of Sweeteners and Recent Trends (Chapter 6). In: J.M. Rippe (Ed.) Fructose, High Fructose Corn Syrup, Sucrose and Health. Springer Science, New York.
• Melanson K.J., Zukley L., Lowndes J. et al. (2007) Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. Nutrition, 23: 103–112.
• Nechaev A.P. (2008) Tehnologii pischevyih proizvodstv. KolosS, Moskva.
• Rizkalla S.W. (2010) Health implications of fructose consumption: a review of recent data. Nutr. Metab. (Lond.), 7: 82.
• Sapronov A.R., Sapronova L.A., Ermolaev S.V. (2013) Tehnologiya sahara. Professiya, Sankt-Peterburg.
• Shangari N., Bruce W.R., Poon R., O’Brien P.J. (2003) Toxicity of glyoxals — role of oxidative stress, metabolic detoxification and thiamine deficiency. Biochem. Soc. Trans., 31(Pt. 6): 1390–1393.
• Sievenpiper J.L., de Souza R.J., Mirrahimi A. et al. (2012) Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann. Intern. Med., 156: 291–304.
• Soenen S., Westerterp-Plantenga M.S. (2007) No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. Am. J. Clin. Nutr., 86: 1586–1594.
• Softic S., Cohen D.E., Kahn C.R. (2016) Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig. Dis. Sci., 61: 1282–1293.
• Stanhope K.L., Griffen S.C., Bair B.R. et al. (2008) Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. Am. J. Clin. Nutr., 87: 1194–1203.
• Sun S.Z., Anderson G.H., Flickinger B.D. et al. (2011) Fructose and non-fructose sugar intakes in the US population and their associations with indicators of metabolic syndrome. Food Chem. Toxicol., 49: 2875–2882.
• Tappy L., Le K.A. (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol. Rev., 90: 23–46.
• Tappy L., Le K.A., Tran C., Paquot N. (2010) Fructose and metabolic diseases: new findings, new questions. Nutrition, 26: 1044–1049.
• Tappy L., Mittendorfer B. (2012) Fructose toxicity: is the science ready for public health actions? Curr. Opin. Clin. Nutr. Metab. Care, 15: 357–361.
• Voloshanenko G.P. (1985) Novoe v tehnike i tehnologii proizvodstva patoki i glyukozyi. Minpischeprom, Kiev.
• Wang D.D., Sievenpiper J.L., de Souza R.J. et al. (2012) The effects of fructose intake on serum uric acid vary among controlled dietary trials. J. Nutr., 142: 916–923.
• White J.S. (2009) Misconceptions about high-fructose corn syrup: is it uniquely responsible for obesity, reactive dicarbonyl compounds, and advanced glycation endproducts? J. Nutr., 139(6): 1219S–1227S.
• White J.S. (2013) Challenging the fructose hypothesis: New perspectives on fructose consumption and metabolism. Adv. Nutr., 4: 246–256.
• White JS, Hobbs LJ, Fernandez S. (2015) Fructose content and composition of commercial HFCS-sweetened carbonated beverages. Int. J. Obes. (Lond), 39(1): 176–182.