Fructose, galactose and glucose – In health and disease


      Background and aims

      Monosaccharides are important components of the diet, where the sweetness of these common sugars draw animals to eat the tissue within which they are located - especially fruits. Higher (larger) saccharides, within which they are constituents, are ubiquitous throughout nature too - and include disaccharides, oligosaccharides and polysaccharides. These may be converted (hydrolysed) to monosaccharides by the plant tissue enzymes during ripening and stimulate consumption by a predator (whereupon seeds within the fruit are dispersed). Predators may have relevant enzymes in their digestive tract to effect conversion of the larger carbohydrates to its monosaccharides - which are then absorbed from the gut and like free monosaccharides in fruit/vegetables, provide an energy source. Starch is an important source of glucose. This review (on monosaccharides) is part one of a series of three which aim to link the role of carbohydrates in food through processing to health and disease related issues. The emphasis here is to understand the role of the three key monosaccharides from the diet - fructose, galactose and glucose - with perspectives in health and disease.


      The review was based on a review of relevant databases for material (e.g. Pubmed, Science Direct, Web of Science, Wiley online library etc.).


      Data pertaining to the nutritional role of key dietary monosaccharides were evaluated together with their utilisation and role in health and disease. Disease states and their management in the context of monosaccharide consumption were considered.


      The body is designed to utilise carbohydrates - where a physiological balance of ingestion, storage and utilisation is critical. In disease states, the balance is lost and a number of carbohydrate based metabolic disorders are established within the medical community. Overall, this review considers digestive and metabolic issues associated with free monosaccharides commonly consumed in the human diet. Further reviews will focus on common di-, oligo and polysaccharides relevant to digestive energy and overall health.


      To read this article in full you will need to make a payment


      Subscribe to Clinical Nutrition ESPEN
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lemoine R.
        Sucrose transporters in plants: update on function and structure.
        Biochim Biophys Acta. 2000; 1465: 246-262
        • Sturm A.
        Invertases. Primary structures, functions and roles in plant development and sucrose partitioning.
        Plant Physiol. 1999; 121: 1-7
        • Gross K.C.
        • Acosta P.B.
        Fruits and vegetables are a source of galactose: implications in planning the diets of patients with galactosaemia.
        J Inherit Metab Dis. 1991; 14: 253-258
        • Food Standards Agency and Public Health England
        McCance and Widdowson's the composition of foods.
        Seventh Summary Edition. RSC, Cambridge2014
        • Ladas S.D.
        • Haritos D.N.
        • Raptis S.A.
        Honey may have a laxative effect on normal subjects because of incomplete fructose absorption.
        Am J Clin Nutr. 1995; 62: 1212-1215
        • Gracey M.
        • Burke V.
        Sugar-induced diarrhoea in children.
        Arch Dis Child. 1973; 48: 331-336
        • Harada N.
        • Inagaki N.
        Role of sodium-glucose transporters in glucose uptake of the intestine and kidney.
        J Diabetes Invest. 2012; 3: 352-353
        • Wright E.M.
        • Martín M.G.
        • Turk E.
        Intestinal absorption in health and disease-sugars.
        Best Pract Res Clin Gastroenterol. 2003; 17: 943-956
        • Wright E.M.
        • Sala-Rabanal M.
        • Loo D.D.F.
        • Hirayama B.A.
        Sugar absorption.
        in: Johnson L.R. Physiology of the gastrointestinal tract. 5th ed. Academic Press, London, Waltham and San Diego2012: 1583-1593
        • Mueckler M.
        • Thorens B.
        The SLC2 (GLUT) family of membrane transporters.
        Mol Asp Med. 2013; 34: 121-138
        • Augustin R.
        • Mayoux E.
        Mammalian sugar transporters, glucose homeostasis.
        in: Szablewski L. Glucose homeostasis. InTech, 2014: 1-36
        • Röder P.V.
        • Geillinger K.E.
        • Zietek T.S.
        • Thorens B.
        • Koepsell H.
        • Daniel H.
        The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing.
        PLoS One. 2014; 9e89977
        • Holst J.J.
        • Gribble F.
        • Horowitz M.
        • Rayner C.K.
        Roles of the gut in glucose homeostasis.
        Diabetes Care. 2016; 39: 884-892
        • Żyżelewicz D.
        • Oracz J.
        • Krysiak W.
        • Budryn G.
        • Nebesny E.
        Effects of various roasting conditions on acrylamide, acrolein, and polycyclic aromatic hydrocarbons content in cocoa bean and the derived chocolates.
        Dry Technol. 2017; 35: 363-374
        • Raters M.
        • Matissek R.
        Acrylamide in cocoa: a survey of acrylamide levels in cocoa and cocoa products sourced from the German market.
        Eur Food Res Technol. 2018; 244: 1381-1388
        • Becalski A.
        • Brady B.
        • Feng S.
        • Gauthier B.R.
        • Zhao T.
        Formation of acrylamide at temperatures lower than 100°C: the case of prunes and a model study.
        Food Addit Contam. 2011; 28: 726-730
        • Azaïs-Braesco V.
        • Sluik D.
        • Maillot M.
        • Kok F.
        • Moreno L.A.
        A review of total & added sugar intakes and dietary sources in Europe.
        Nutr J. 2017; 16: 6
        • Goldenberg R.
        • Punthakee Z.
        • Canadian Diabetes Association Clinical Practice Guidelines Expert Committee
        Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome.
        Can J Diabetes. 2013; 37: S8-S11
        • Kharroubi A.T.
        • Darwish H.M.
        Diabetes mellitus: the epidemic of the century.
        World J Diabetes. 2015; 6: 850-867
        • Clemens R.A.
        • Jones J.M.
        • Kern M.
        • Lee S.-Y.
        • Mayhew E.J.
        • Slavin J.L.
        • et al.
        Functionality of sugars in foods and health.
        Compr Rev Food Sci Food Saf. 2016; 15: 433-470
        • MacDonald I.A.
        A review of recent evidence relating to sugars, insulin resistance and diabetes.
        Eur J Nutr. 2016; 55: S17-S23
        • Nuttall F.Q.
        • Gannon M.C.
        Dietary management of Type 2 diabetes: a personal odyssey.
        J Am Coll Nutr. 2007; 26: 83-94
        • Gonzalez J.T.
        • Fuchs C.J.
        • Betts J.A.
        • van Loon L.J.C.
        Glucose plus fructose ingestion for post-exercise recovery-greater than the sum of its parts?.
        Nutrients. 2017; 9: 1-15
        • Sanders T.A.B.
        How important is the relative balance of fat and carbohydrate as sources of energy in relation to health? Conference on ‘Nutrition at key life stages: new findings, new approaches’, Symposium 1: nutritional issues in adolescence and adulthood.
        Proc Nutr Soc. 2016; 75: 147-153
        • Scapini T.
        • Fernandes A.C.
        • Proença R.P.D.
        Added sugars: definitions, classifications, metabolism and health implications.
        Br J Nutr. 2017; 30: 663-677
        • Aller E.E.J.G.
        • Abete I.
        • Astrup A.
        • Martinez J.A.
        • van Baak M.A.
        Starches, sugars and obesity.
        Nutrients. 2011; 3: 341-369
        • Henry C.J.K.
        • Thondre P.S.
        The glycaemic index: concept, recent developments and its impact on diabetes and obesity. Access Not Excess.
        Charles Pasternak. Smith-Gordon, 2011: 154-175 (Chapter 15)
        • Wolever T.M.S.
        The glycaemic index. A physiological classification of dietary carbohydrate.
        CABI, Wallingford2006: 62-82
        • Jin J.
        Over-the-counter laxatives.
        JAMA Patient Page. 2014; 312: 1167
        • Canani R.B.
        • Pezzella V.
        • Amoroso A.
        • Cozzolino T.
        • Di Scala C.
        • Passariello A.
        Diagnosing and treating intolerance to carbohydrates in children.
        Nutrients. 2016; 8: 1-16
        • Touger-Decker R.
        • van Loveren C.
        Sugars and dental caries.
        Am J Clin Nutr. 2003; 78: 881S-892S
        • Zero D.T.
        Sugars - the arch criminal?.
        Caries Res. 2004; 38: 277-285
        • Gupta P.
        • Gupta N.
        • Pawar A.P.
        • Birajdar S.S.
        • Natt A.S.
        • Singh H.P.
        Role of sugar and sugar substitutes in dental caries: a review.
        ISRN Dent. 2013; (Article ID 519421): 5
        • Hawkes N.
        WHO may revise guideline on sugar to combat tooth decay.
        BMJ. 2014; 348: g21
        • Jovanovic-Malinovska R.
        • Kuzmanova S.
        • Winkelhausen E.
        Oligosaccharide profile in fruits and vegetables as sources of prebiotics and functional foods.
        Int J Food Prop. 2014; 17: 949-965
        • Steinmann B.
        • Santer R.
        • van den Berghe G.
        Disorders of fructose metabolism.
        in: Fernandes J. Saudubray J.-M. van den Berghe G. Walter J.H. Inborn metabolic diseases: diagnosis and treatment. Springer Medizin Verlag, Berlin and Heidelberg2006: 135-142
        • Pyhtila B.M.
        • Shaw K.A.
        • Neumann S.E.
        • Fridovich-Keil J.L.
        Newborn screening for galactosemia in the United States: looking back, looking around, and looking ahead.
        J Inherit Metab Dis Rep. 2015; 15: 79-93
        • Kim H.-O.
        • Hartnett C.
        • Scaman C.H.
        Free galactose content in selected fresh fruits and vegetables and soy beverages.
        J Agric Food Chem. 2007; 55: 8133-8137
        • Pereira P.C.
        Milk nutritional composition and its role in human health.
        Nutrients. 2014; 30: 619-627
        • Walter J.H.
        • Collins J.E.
        • Leonard J.V.
        Recommendations for the management of galactosaemia.
        Arch Dis Child. 1999; 80: 93-96
        • Berry G.T.
        • Segal S.
        • Gitzelmann R.
        Disorders of galactose metabolism.
        in: Fernandes J. Saudubray J.-M. van den Berghe G. Walter J.H. Inborn metabolic diseases - diagnosis and treatment. Springer Medizin Verlag, Heidelberg2006: 121-130
        • Bosch A.M.
        Classic galactosaemia: dietary dilemmas.
        J Inherit Metab Dis. 2011; 34: 257-260
        • Welling L.
        • Bernstein L.E.
        • Berry G.T.
        • Burlina A.B.
        • Eyskens F.
        • Gautschi M.
        • et al.
        International clinical guideline for the management of classical galactosaemia: diagnosis, treatment, and follow-up.
        J Inherit Metab Dis. 2017; 40: 171-176
        • Coelho A.I.
        • Berry G.T.
        • Rubio-Gozalbo M.E.
        Galactose metabolism and health.
        Curr Opin Clin Nutr Metab Care. 2015; 18: 422-427
        • Coelho A.I.
        • Rubio-Gozalbo M.E.
        • Vicente J.B.
        • Rivera I.
        Sweet and sour: an update on classic galactosaemia.
        J Inherit Metab Dis. 2017; 40: 325-342
        • Demirbas D.
        • Coelho A.I.
        • Rubio-Gozalbo M.E.
        • Berry G.T.
        Hereditary galactosaemia.
        Metab Clin Exp. 2018; 83: 188-196
        • Bosch A.M.
        • Bakker H.D.
        • Wenniger-Prick L.J.M.
        • Wanders R.J.A.
        • Wijburg F.A.
        High tolerance for oral galactose in classical galactosaemia: dietary implications.
        Arch Dis Child. 2004; 89: 1034-1036
        • van Wijk R.
        • van Solinge W.W.
        The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis.
        Blood. 2005; 106: 4034-4042
        • Hall G.W.
        Understanding haemolytic anaemia.
        Paediatr Child Health. 2007; 17: 333-339
        • Gallagher P.G.
        Haemolytic anaemias: red cell membranes and metabolic defects.
        in: Goldman L. Schafer A.I. Goldman's cecil medicine. 24th ed. Elsevier Saunders, Philadelphia2012: e25-e33
        • Bianchi P.
        • Mohandas N.
        Hereditary disorders of the red cell membrane and disorders of red cell metabolism.
        in: Hoffbrand A.V. Higgs D.R. Keeling D.M. Mehta A.B. Postgraduate haematology. 7th ed. Wiley-Blackwell, New Jersey2016: 114-137
        • Patel K.P.
        • O'Brien T.W.
        • Subramony S.H.
        • Shuster J.
        • Stacpoole P.W.
        The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.
        Mol Genet Metab. 2012; 105: 34-43
        • De Meirleir L.J.
        • Van Coster R.
        • Lissens W.
        Disorders of pyruvate metabolism and the tricarboxylic acid cycle.
        in: Fernandes J. Saudubray J.-M. van den Berghe G. Walter J.H. Inborn metabolic diseases - diagnosis and treatment. Springer Medizin Verlag, Heidelberg2006: 161-174
        • Jitrapakdee S.
        • St. Maurice M.
        • Rayment I.
        • Cleland W.W.
        • Wallace J.C.
        • Attwood P.V.
        Structure, mechanism and regulation of pyruvate carboxylase.
        Biochem J. 2008; 413: 369-387
        • Yang J.
        • Kalhan S.C.
        • Hanson R.W.
        What is the metabolic role of phosphoenolpyruvate carboxykinase?.
        J Biol Chem. 2009; 284: 27025-27029
        • Bhattacharya K.
        • Orton R.C.
        • Qi X.
        • Mundy H.
        • Morley D.W.
        • Champion M.P.
        • et al.
        A novel starch for the treatment of glycogen storage diseases.
        J Inherit Metab Dis. 2007; 30: 350-357
        • Correia C.E.
        • Bhattacharya K.
        • Lee P.J.
        • Shuster J.J.
        • Theriaque D.W.
        • Shankar M.N.
        • et al.
        Use of modified cornstarch therapy to extend fasting in glycogen storage disease type Ia and Ib1-3.
        Am J Clin Nutr. 2008; 88: 1272-1276
        • Bhattacharya K.
        Dietary dilemmas in the management of glycogen storage disease type I.
        J Inherit Metab Dis. 2011; 34: 621-629
        • Bhattacharya K.
        Investigation and management of the hepatic glycogen storage diseases.
        Transl Pediatr. 2015; 4: 181-189
        • Bhattacharya K.
        • Mundy H.
        • Lilburn M.F.
        • Champion M.P.
        • Morley D.W.
        • Maillot F.
        A pilot longitudinal study of the use of waxy maize heat modified starch in the treatment of adults with glycogen storage disease type I: a randomised double-blind cross-over study.
        Orphanet J Rare Dis. 2015; 10: 18
        • Jang C.
        • Hui S.
        • Lu W.
        • Cowan A.J.
        • Morscher R.J.
        • Lee G.
        • et al.
        The small intestine converts dietary fructose into glucose and organic acids.
        Cell Metab. 2018; 27: 351-361
        • Lorenzi M.
        The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive and resilient.
        Exp Diabetes Res. 2007;
        • Latulippe M.E.
        • Skoog S.M.
        Fructose malabsorption and intolerance: effects of fructose with and without simultaneous glucose ingestion.
        Crit Rev Food Sci Nutr. 2011; 51: 583-592
        • Ebert K.
        • Witt H.
        Fructose malabsorption.
        Mol Cell Pediatr. 2016; 3: 1-5
        • Tran C.
        Inborn errors of fructose metabolism. What can we learn from them.
        Nutrients. 2017; 9: 1-8
        • Wright E.M.
        Genetic disorders of membrane transport I. Glucose galactose malabsorption.
        Am J Physiol Gastrointest Liver Physiol. 1998; 275 (38): G879-G882
        • Lai K.
        • Elsas L.J.
        • Wierenga K.J.
        Galactose toxicity in animals.
        IUBMB Life. 2009; 61: 1063-1074
        • Smit G.P.A.G.
        • Rake J.P.
        • Akman H.O.
        • DiMauro S.
        The glycogen storage diseases and related diseases.
        in: Fernandes J. Saudubray J.-M. van den Berghe G. Walter J.H. Inborn metabolic diseases - diagnosis and treatment. Springer Medizin Verlag, Berlin and Heidelberg2006: 101-120
        • Mayatepek E.
        • Hoffmann B.
        • Meissner T.
        Inborn errors of carbohydrate metabolism.
        Best Pract Res Clin Gastroenterol. 2010; 24: 607-618
        • Bhattacharya K.
        Investigation and management of the hepatic glycogen storage diseases.
        Transl Pediatr. 2015; 4: 240-248
        • Kishnani P.S.
        • Chen Y.-T.
        Disorders of carbohydrate metabolism.
        in: Rimoin D.L. Pyeritz R.E. Korf B. Emery and rimoin's principles and practice of medical genetics. 6th ed. Academic Press, 2013: 1-36
        • Weinstein D.A.
        • Steuerwald U.
        • De Souza C.F.M.
        • Derks T.G.J.
        Inborn errors of metabolism with hypoglycaemia. Glycogen storage diseases and inherited disorders of gluconeogenesis.
        Pediatr Clin North Am. 2018; 65: 247-265