Isomaltulose

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Isomaltulose
Isomaltulose structure.svg
Names
IUPAC name
6-O-α-D-Glucopyranosyl-D-fructose
Other names
Palatinose™
Identifiers
13718-94-0 YesY
ChemSpider 75509 YesY
EC number 237-282-1
Jmol-3D images Image
PubChem 83686
Properties
C12H22O11
Molar mass 342.30 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 YesY verify (what isYesY/N?)
Infobox references

Isomaltulose is a disaccharide carbohydrate composed of glucose and fructose linked by an alpha-1,6-glycosidic bond (chemical name: 6-0-α-D-glucopyranosyl-D-fructose). It is naturally present in honey[1] and sugar cane extracts.[2] It tastes similar to sucrose with half the sweetness. Isomaltulose is also known by the trade name Palatinose™, which is manufactured by enzymatic rearrangement (isomerization) from sucrose. The enzyme and its source were discovered in Germany in 1950.[3] After evaluation of its basic physiology—reviewed[4]—it has been used as a sugar alternative in foods in Japan since 1985, in the EU since 2005, in the US since 2006, and in Australia and New Zealand since 2007, besides numerous other countries worldwide where isomaltulose can be found today. Characterization, purity and analytical methods for commercial isomaltulose are laid down for example, in the Food Chemical Codex.[5] Physical and physiological properties of isomaltulose (Palatinose) have been summarised;[6] its physical properties closely resemble those of sucrose making it easy to use in existing recipes and processes.

  • Isomaltulose is not to be confused with isomalt, which is a disaccharide polyol from sugar origin, used as sugar replacer in sugar-free candies and confectionery, and which nutritionally (unlike isomaltulose) is a low-digestible carbohydrate with fiber like physiology.

The last decade has seen considerable interest in isomaltulose. Like sucrose (table sugar) it can be digested to glucose and fructose. However, it differs from sucrose in one highly important respect. While in sucrose the glucose and fructose are bonded together with a linkage called α1-2, in isomaltulose the linkage is α1-6. This difference results in profoundly different effects on human (and animal) physiology with multiple potential health benefits when isomaltulose is consumed in place of sucrose and certain other carbohydrates. The benefits arise because, in comparison with sucrose and most other carbohydrates, isomaltulose is digested slowly and steadily by humans and animals, and is essentially no substrate for oral bacteria (i.e. isomaltulose is kind to teeth by not promoting tooth decay).[6]

Function[edit]

Basically, isomaltulose has the same function as sucrose; that is as an energy source that keeps the human body and brain functioning. The similarities even extend to how both of these substances taste and are processed.[4]

Available carbohydrate[edit]

Isomaltulose is an available carbohydrate like sucrose and most others sugars or maltodextrins. Available or “nutritive” carbohydrates serve the body as a source of energy for its physiological functions. Whether a carbohydrate becomes available to the body largely depends on its digestion, absorption and metabolism.

  • A carbohydrate that is absorbed (with or without prior digestion) and is fully metabolised in humans (i.e. is not excreted into urine) is known to nutritionists as ‘available carbohydrate’.[7]

When present in foods and beverages that are ingested by humans, isomaltulose is essentially completely digested and absorbed.[8] Its intestinal digestion involves the enzyme isomaltase, which is located in the wall of the small intestine. This enzyme is otherwise involved in the digestion of α-1,6 linkages present in starch. The products of isomaltulose digestion are glucose and fructose, which enter blood. Once absorbed, the glucose and fructose follow the same metabolic routes through the body as if they were derived from sucrose.[4] While fructose is converted to glucose in the liver, glucose from the small intestine and liver is distributed via blood to different parts of the body where it serves cellular metabolism as an energy source.

Source of energy[edit]

Based on the heat released on complete burning of isomaltulose, and the essentially complete physiological availability of carbohydrate from isomaltulose,[8][9] the food energy value of isomaltulose is identical to that of sucrose. For both, the caloric value of 4 kcal/g (17 kJ/g) for available carbohydrates applies in food labelling or dietary planning.

Slow and sustained release[edit]

Isomaltulose is a slow and sustained release carbohydrate: After ingestion, the enzymatic digestion of sucrose and isomaltulose occur on the same sucrase-isomaltase enzyme complex, which is located in the small intestine.[7][10] Several studies show this complex to digest isomaltulose (via isomaltase) slowly compared with sucrose (via sucrase) (Vmax differ by a factor of 4.5 fold).[11]

As a result of its slow digestion, isomaltulose occurs more distally in the human small intestine than does sucrose. This is evidenced by their different incretion hormones responses. The hormone GIP (glucose-dependent insulinotropic polypeptide) is secreted from the earlier (proximal) part of the small intestine in lower amounts after isomaltulose than for sucrose ingestion, whereas the hormone GLP-1 (glucagon-like peptide-1) is secreted from later (distal) parts of the small intestine in higher amounts with isomaltulose compared with sucrose.[12][13]

Compared with sucrose, the absorption of energy as carbohydrate from isomaltulose is prolonged, as was illustrated for example by Ang and Linn in 2014.[13] The resulting steady and sustained energy supply to the body from isomaltulose is reflected in the shape of the blood glucose response, which demonstrates the slow and sustained release of energy from this dietary carbohydrate.

Lower blood glucose and insulin response[edit]

Slow digestion and distal absorption of carbohydrate from isomaltulose contributes to the low blood glucose response to isomaltulose ingestion and to the associated low insulin release. In comparison with sucrose, the rise in blood glucose concentration following the ingestion of isomaltulose appears slower and attenuated, with a lower amplitude that is sustained over a longer period of time. Isomaltulose has a low glycaemic index (GI). A GI of 32 for isomaltulose was determined by the University of Sydney Glycaemic Index Research Service, who list isomaltulose (Palatinose™) in their searchable GI database.[14] The GI value of 32 compares with one of 67 for sucrose and 100 for glucose, which makes isomaltulose a very low GI carbohydrate.

The low glycaemic response to isomaltulose has been confirmed in numerous studies for different population groups including healthy people, overweight or obese persons, and individuals in a pre-diabetic state and persons with manifest type 1 or type 2 diabetes (e.g.[9][15][16][17][12][13][18]). Among these studies, all show the lower blood glucose response of isomaltulose and where tested also show the associated reduction in the blood insulin response. A significant role for the incretin hormone GLP-1 has been established, which occurs in response to distal carbohydrate absorption and limits the rise in blood glucose concentration after a meal.[12][13]

A claim corresponding to the low glycaemic response of isomaltulose and its potential to lower the blood glucose response of foods when replacing others sugars has been approved and laid down in EU legislation[19] following the publication of a positive opinion from the European Food Safety Authority.[20]

Improvements to blood glucose control[edit]

In the long-term when eating a diet including carbohydrate, reducing undesirably high concentrations of glucose in blood, and the associated demand for insulin, is supportive of the prevention and management of diabetes mellitus, cardiovascular disease, and possibly overweight and obesity—as indicated by the International Carbohydrate Quality Consortium consensus of expert nutrition scientists.[21] A lower glycemic diet can be achieved by choosing foods with low or reduced glycemic properties instead of many commonly consumed foods. Isomaltulose in place of sucrose and many other carbohydrates has enabled the glycemic profile of foods to be reduced.

Several studies have looked at the longer-term effects of dietary sugar replacement with isomaltulose for the management of both blood glucose control and lipid metabolism in both diabetic and non-diabetic persons. The studies provide evidence of improvements to both aspects of metabolism upon regular isomaltulose consumption when compared with certain other carbohydrates such as sucrose, maltodextrin or glucose (e.g.[16][22][23][24][25][26]).

Effect on fat oxidation[edit]

When compared with other ingested carbohydrates, isomaltulose allows higher rates of fat oxidation to fuel energy demanding processes in the body—as noted below for various circumstances. Mechanisms for this can be explained: Ingested carbohydrates that cause a higher blood glucose concentration stimulate a higher release of insulin both to facilitate the uptake of glucose by tissues and to normalise the blood glucose concentration. The higher insulin concentration also promotes carbohydrate oxidation at the expense of fat oxidation, thus promoting fat retention and storage in adipose tissue. Thus, ingested isomaltulose with its slower, steadier and longer time for release of glucose into blood allows the supply of carbohydrate energy to be steady for longer—meanwhile creating a more advantageous metabolic profile: That is, demand for insulin is lower after isomaltulose ingestion than it is for higher glycaemic carbohydrates. The associated lower insulin release and concentration thereby allow a person eating isomaltulose to maintain higher rates of fat oxidation in energy metabolism. The lower insulin concentration is also expected to lower the recycling by liver of circulating free-fatty acids back to adipose tissue via plasma triglycerides, a process that supports both fat oxidation and lowering of fat storage. Practical implications seem to be several, higher rates of fat oxidation occur after isomaltulose than after ingestion of higher glycaemic carbohydrates in many studies, yet the studies have different focuses:

  • Isomaltulose in weight management and body composition

Some studies have looked at the effects of replacing sugars with isomaltulose in meals or drinks on metabolic responses and fat oxidation in healthy or overweight to obese adults with normal or impaired glucose tolerance in largely sedentary conditions.[17][27][28][29] These studies evidently see the relevance in weight management and body composition. Longer-term studies suggest, indeed, that isomaltulose has a role in reducing body fatness, at least central obesity. In these studies, abdominal fat decreased with sugar replacement by isomaltulose or when replacing breakfast calories.[16][22][23]

  • Isomaltulose in physical activity and sports nutrition

Others studies have looked at the potential of the slow and sustained release of carbohydrate energy from isomaltulose compared with other ingested carbohydrates, finding higher rates of fat oxidation in endurance activities when preserving glycogen is important.[28][30] In addition, recently published trials with a recovery protein drink suggest that the addition of isomaltulose and a nutritional supplement (β-hydroxy- β-methylbutyrate) may enhance recovery from resistance exercise—contributing to reduction of muscle damage and improvement of athletic performance.[31]

  • Isomaltulose in type 1 diabetes patients engaging in physical activity

In people with type-1 diabetes, the ingestion of isomaltulose instead of glucose during moderate carbohydrate loading before exercise has resulted in improvements in their glycaemic control, protection against hypoglycaemia, and maintenance of their running performance.[32][33] The reduced risk of exercise-induced hypoglycaemia arises in part from the lower demand for insulin injection (50% lower) when using isomaltulose and in part from the simultaneous higher contribution of fat oxidation to energy metabolism, which reserves energy in carbohydrate to counter the risk of hypoglycaemia.

Cognitive performance (mood and memory)[edit]

Carbohydrates and the glucose they supply influence cognitive performance. The sustained glucose release from isomaltulose has particular advantages in the late phase after a meal. Several studies comparing isomaltulose with higher glycaemic carbohydrates when eaten with breakfast by healthy children, middle-age adults, and aged adults, show improvements in mood and memory after the isomaltulose.[34][35][36][37]

Oral health[edit]

Isomaltulose is ‘kind to teeth’. The fermentation of carbohydrates by oral bacteria is responsible for the formation of dental plaque and oral acids, which initiate tooth demineralisation and dental caries (tooth decay). Isomaltulose largely resists hydrolysis, digestion and fermentation by oral bacteria and is the first carbohydrate of its kind to show negligible acid production on teeth by pH telemetry. The evidence is strong and has provided the basis for ‘toothkind’ claims approved by both the Food and Drug Administration in the USA[38][39] and the European Authorities with a respective claim following a positive opinion from the European Food Safety Authority in the EU.[20]

Use[edit]

Isomaltulose is used as a food ingredient and alternative to other sugars and maltodextrins in foods and beverages. Thus isomaltulose has a pure and natural sucrose-like sweetness profile, a sweetening power about a half that of sucrose, and no aftertaste.[6] Because isomaltulose has very low hygroscopicity (moisture absorption), in instant powders (e.g drinks) it maintains free-flowing properties (low risk of lumping). Moreover, isomaltulose is highly stable during processing including acidic conditions and environments where bacteria might grow. In sports beverages, for instance, isotonicity (osmotic pressure equal to that of fluids in the body) can be maintained during storage over the beverage’s shelf-life.

Products in which isomaltulose finds application include, for example, baked goods, pastry glazings and icings, breakfast cereals, cereal bars, dairy produce, sugar confectionery (e.g. chocolates, jellies, chewy confections and chewing or bubble gum), frozen desserts, fruit-juice beverages, malt beverages, sports beverages, energy drinks, instant drinks, special and clinical nutrition feeds and more.[6][40]

The use of isomaltulose in foods and drinks is recognised in many regions worldwide. For example, it is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration,[40] is approved as a novel food by the European Commission,[41] and in Japan has the status FOSHU (food for specific health use).[42]

References[edit]

  1. ^ Siddiqua, I.R; Furgala, B (1967). "Isolation and characterization of oligosaccharides from honey". Journal of Apicultural Research 6 (3): 139–145. 
  2. ^ Egglestone, G; Grisham, M (2003). "Oligosaccharides in cane and their formation on cane deterioration". ACS Symposium Series 849 (16): 211–232. 
  3. ^ Weidenhagen, R; Lorenzo, A.D (1957). "Palatinose (6-0-alpha-D-glucopyranosyl-D-fructofuranose), ein neues bakterielles Umwandlungsprodukt der Saccharose [Palatinose (6-0-alpha-D-glucopyranosyl-D-fructofuranose), a new bacterial conversion of sucrose product]". Zeitschrift fur die Zuckeridustrie, Fachorgan fur Tecknik, Rubenbau und Wirtschaft 7: 533–534. 
  4. ^ a b c Lina, B.A.R.; Jonker, D.; Kozianowski, G. (2002). "Isomaltulose (Palatinose®): A review of biological and toxicological studies". Food and Chemical Toxicology 40 (10): 1375–81. doi:10.1016/S0278-6915(02)00105-9. PMID 12387299. 
  5. ^ Food Chemical Codex (2010). Monograph on Isomaltulose (7th ed.). Rockville, MD 20852-1790: US Pharmacopeial Convention. pp. 546–548. ISBN 9781889788852. 
  6. ^ a b c d Sentko, A. and Willibald-Ettle, I. (2012). "Isomaltulose." In: Sweeteners and Sugar Alternatives in Food Technology, 2nd Ed. Editors O'Donnell, K. & Kearsley, M.W. Wiley-Blackwell. Oxford, UK. ISBN 978-0-470-65968-7
  7. ^ a b Livesey, G (2014). "Carbohydrate Digestion, Absorption, and Fiber". Reference Module in Biomedical Sciences. doi:10.1016/B978-0-12-801238-3.00043-X.  http://www.sciencedirect.com/science/article/pii/B978012801238300043X
  8. ^ a b Holub, I; Gostner, A; Theis, S; Nosek, L; Kudlich, T; Melcher, R; Scheppach, W. (2010). "Novel findings on the metabolic effects of the low glycaemic carbohydrate isomaltulose (Palatinose™)". British Journal of Nutrition 103 (12): 1730–7. doi:10.1017/S0007114509993874. PMC 2943747. PMID 20211041. 
  9. ^ a b Macdonald, I; Daniel, J (1983). "The bioavailability of isomaltulose in man and rat". Nutrition Reports International 28 (5): 1083–1090. 
  10. ^ Dahlqvist, A; Auricchio, S; Semenza, G; Prader, A (1963). "Human intestinal disaccharidases and hereditary disaccharide intolerance". Journal of Clinical Investigations 42: 556–562. doi:10.1172/JCI104744. 
  11. ^ Sentko, A; Bernard, J (2011). Isomaltulose In: Alternative Sweeteners. Ed: L. O'Brien Nabors (4th ed.). Boca Raton,London, New York: CRC Press, Taylor & Francis Group. pp. 423–438. ISBN 978-1-4398-4614-8.  e-book ISBN 978-1-4398-4615-5
  12. ^ a b c Maeda, A; Miyagawa, J; Miuchi, M; Nagai, E; Konishi, K; Matsuo, T; Tokuda, M; Kusunoki, Y; Ochi, H; Murai, K; Katsuno, T; Hamaguchi, T; Harano, Y; Namba, M (2013). "Effects of the naturally-occurring disaccharides, palatinose and sucrose, on incretin secretion in healthy non-obese subjects". Journal of Diabetes Investigation 4 (3): 281–286. doi:10.1111/jdi.12045. PMC 4015665. 
  13. ^ a b c d Ang, M; Linn, T (2014). "Comparison of the effects of slowly and rapidly absorbed carbohydrates on postprandial glucose metabolism in type 2 diabetes mellitus patients: a randomized trial". American Journal of Clinical Nutrition 100 (4): 1059–1068. doi:10.3945/ajcn.113.076638. 
  14. ^ University of Sydney, Glycaemic Index Research Service. "Search for the Glycaemic Index". Retrieved 12 July 2015. 
  15. ^ Kawai, K; Okuda, Y; Yamashita, K (1983). "Changes in blood glucose and insulin after an oral palatinose administration in normal subjects". Endocrinology Japan 32 (6): 933–936. 
  16. ^ a b c Yamori, Y; Mori, M; Mori, H; Kashimura, J,; Sakuma, T; Ishikawa, P.M; Moriguchi, E; Moriguchi, Y (2007). "Japanese perspective for lifestyle disease risk reduction in immigrant Japanese Brazilians—A double-blind placebo-controlled intervention study on palatinose". Clinical and Experimental Pharmacology and Physiology 34: S5–S7. doi:10.1111/j.1440-1681.2007.04759.x. 
  17. ^ a b >van Can, J.G; Ijzerman, T.H; van Loon, L.J; Brouns, F; Blaak, E.E (2009). "Reduced glycaemic and insulinaemic responses following isomaltulose ingestion: implications for postprandial substrate use". British Journal of Nutrition 102 (10): 1408–1413. doi:10.1017/S0007114509990687. 
  18. ^ König, D; Theis, S; Kozianowski, G; Berg, A (2012). "Postprandial substrate use in overweight subjects with the metabolic syndrome after isomaltulose (Palatinose) ingestion". Nutrition 26 (6): 651–656. doi:10.1016/j.nut.2011.09.019. 
  19. ^ European Union (EU) Legislation, Annex. "Commission Regulation of 16 May 2012 establishing a list of permitted health claims made on foods, other than those referring to the reduction of disease risk and to children’s development and health". Retrieved 12 July 2015. 
  20. ^ a b European Food Safety Authority, 2011. "Scientific Opinion on the substantiation of health claims related to the sugar replacers… isomaltulose …and maintenance of tooth mineralisation by decreasing tooth demineralisation…, and reduction of post-prandial glycaemic responses … pursuant to Article 13(1) of Regulation (EC) No 1924/2006" (PDF). ESFA Journal 9 (4): 2076, 1–25. Retrieved 12 July 2015. 
  21. ^ Augustin, L.S.A; Kendall, C.W.C; Jenkins, D.J.A; Willett, W.C; Astrup, A; Barclay, A.W; Björck, I; Brand-Miller, J.C; Brighenti, F; Buyken, A.E; Ceriello, A; La Vecchia, C; Livesey, G; Liu, S; Riccardi, G; Rizkalla, S.W; Sievenpiper, J.L; Trichopoulou, T; Wolever, T.M.S; Baer-Sinnott, S; Poli, A (2014). "Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC)". Nutrition, Metabolism and Cardiovascular Diseases. doi:10.1016/j.numecd.2015.05.005. Retrieved 12 July 2015. 
  22. ^ a b Oizumi, T; Daimon, D; Jimbu, Y; Kameda, W; Arawaka, N; Yamaguchi, H; Ohnuma, H; Sasaki, H; Kato, T (2007). "A palatinose-based balanced formula improves glucose tolerance, serum free fatty acid levels and body fat composition". Tohoku Journal of Experimental Medicine 212 (2): 91–99. 
  23. ^ a b Okuno, M; Kim, M.K; Mizu, M; Mori, M; Mori, H; Yamori, Y (2010). "Palatinose-blended sugar compared with sucrose: different effects on insulin sensitivity after 12 weeks supplementation in sedentary adults". International Journal of Food Science and Technology 61 (6): 643–651. doi:10.3109/09637481003694576. 
  24. ^ Sakuma, M; Arai, H; Mizuno, A; Fukaya, M; Matsuura, M; Sasaki, H; Yamanaka-Okumura, H; Yamamoto, H; Taketani, Y; Doi, T; Takeda, E (2009). "Improvement of glucose metabolism in patients with impaired glucose tolerance or diabetes by long-term administration of a palatinose-based liquid formula as a part of breakfast". Journal of Clinical Biochemistry and Nutrition 45 (2): 155–162. doi:10.3164/jcbn.09-08. PMC 273627. 
  25. ^ Brunner, S; Holub, I; Theis, S; Gostner, A; Melcher, R; Wolf, P; Amann-Gassner, U; Scheppach, W; Hauner, H (2012). "Metabolic effects of replacing sucrose by isomaltulose in subjects with type 2 diabetes: a randomized double-blind trial". Diabetes Care 35 (6): 1249–1251. doi:10.2337/dc11-1485. 
  26. ^ Fujiwara, T; Naomoto, Y; Motoki, T; Shigemitsu, K; Shirakawa, Y; Yamatsuji, T; Kataoka, M; Haisa, M; Fujiwara, T; Egi, M; Morimatsu, H; Hanazaki, M; Katayama, H; Morita, K; Mizumoto, K; Asou, T; Arima, H; Sasaki, H; Matsuura, M; Gunduz, M; Tanaka, N (2007). "Effects of a novel palatinose based enteral formula (MHN-01) carbohydrate-adjusted fluid diet in improving the metabolism of carbohydrates and lipids in patients with esophageal cancer complicated by diabetes mellitus". Journal of Surgical Research 138 (2): 231–240. doi:10.1016/j.jss.2006.06.025. 
  27. ^ Arai, H; Mizuno, A; Sakuma, M; Fukaya, M; Matsuo, K; Muto, K; Sasaki, H; Matsuura, M; Okumura, H; Yamamoto, H; Taketani, Y; Doi, T; Takeda, E (2007). "Effects of a palatinose-based liquid diet (Inslow) on glycemic control and the second-meal effect in healthy men". Metabolism 56 (1): 115–121. doi:10.1016/j.metabol.2006.09.005. 
  28. ^ a b König, D; Luther, W; Polland, V; Theis, S; Kozianowski, G; Berg, A (2007). "Metabolic effects of low-glycemic Palatinose™ during long-lasting endurance exercise". Annals of Nutrition and Metabolism 51 (Supp 1): 61. 
  29. ^ van Can, J.G; van Loon, L.J; Brouns, F; Blaak, E.E (2012). "Reduced glycaemic and insulinaemic responses following trehalose and isomaltulose ingestion: implications for postprandial substrate use in impaired glucose-tolerant subjects". British Journal of Nutrition 108 (7): 1210–1217. doi:10.1017/S0007114511006714. 
  30. ^ Achten, J; Jentjens, R.L; Brouns, F; Jeukendrup, A.E (2007). "Exogenous oxidation of isomaltulose is lower than that of sucrose during exercise in men". Journal of Nutrition 137 (5): 1143–1148. 
  31. ^ Kraemer, W.J; Hooper, D.R; Szivak, T.K; Kupchak, B.R; Dunn-Lewis, C; Comstock, B.A; Flanagan, S.D; Looney, D.P; Sterczala, A.J; DuPont, W.H; Pryor, J.L; Luk, H.Y; Maladoungdock, J; McDermott, D; Volek, J.S; Maresh, C.M (2015). "The Addition of Beta-hydroxy-beta-methylbutyrate and Isomaltulose to Whey Protein Improves Recovery from Highly Demanding Resistance Exercise". Journal of the American College of Nutrition 34 (2): 91–99. doi:10.1080/07315724.2014.93879. 
  32. ^ Bracken, R.M; Gray, B; Page, R; West, D.J; Stephens, J.W; Bain, S.C (2011). "Isomaltulose tightens pre-exercise glycaemia and produces similar run performance in type 1 diabetes". Diabetologia 54: S253. doi:10.1007/s00125-011-2276-4. 
  33. ^ Bracken, R.M; Page, R; Gray, B; Kilduff, L.P; West, D.J; Stephens, J.W; Bain, S.C (2012). "Isomaltulose improves glycemia and maintains run performance in type 1 diabetes". Medicine and Science in Sports and Exercise 44 (5): 800–808. doi:10.1249/MSS.0b013e31823f6557. 
  34. ^ Taib, M.N; Shariff, Z.M; Wesnes, K.A; Saad, H.A; Sariman, S (2012). "The effect of high lactose-isomaltulose on cognitive performance of young children. A double blind cross-over design study". Appetite 56 (1): 81–87. doi:10.1016/j.appet.2011.09.004. 
  35. ^ Sekartini, R; Wiguna, T; Bardosono, S; Novita, D; Arsianti, T; Calame, W; Schaafsma, A (2013). "The effect of lactose-isomaltulose-containing growing-up milks on cognitive performance of Indonesian children: a cross-over study". British Journal of Nutrition 110 (6): 1089–1097. doi:10.1017/S0007114513000135. 
  36. ^ Young, H; Benton, D (2014). "The effect of using isomaltulose (Palatinose) to modulate the glycaemic properties of breakfast on the cognitive performance of children". European Journal of Nutrition, published online. doi:10.1007/s00394-014-0779-8. 
  37. ^ Young, H; Benton, D (2014). "The glycemic load of meals, cognition and mood in middle and older aged adults with differences in glucose tolerance: A randomized trial". e_SPEN Journal 9 (4): e147–e154. doi:10.1016/j.clnme.2014.04.003. 
  38. ^ Department of Health and Human Services- Food and Drug Administration, 2007. "21 CFR Part 101 (Docket No 2006P-0487) Food labeling, health claims, dietary non-cariogenic carbohydrate sweeteners and dental caries" (PDF). Federal register 72 (179). pp. 527–783. Retrieved 12 July 2015. 
  39. ^ Department of Health and Human Services - Food and Drug Administration, 2008. "21 CFR Part 101 [Docket No. FDA-2006-P-0404 (Formerly Docket No. 2006P-0487] Food labeling: health claims; dietary noncariogenic carbohydrate sweeteners and dental caries. Final rule" (PDF). Federal register 73 (102). pp. 30299–30301. Retrieved 12 July 2015. 
  40. ^ a b Food and Drug Administration, 2006. "Agency Response Letter GRAS Notice No. GRN 000184". Retrieved 14 July 2015. 
  41. ^ European Commission Decision, 25 July 2005. "Authorising the placing on the market of isomaltulose as a novel food or novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council (2005/581/EC)". Retrieved 14 June 2015. 
  42. ^ Japanese Ministry of Health, Labour and Welfare. "Food for Specified Health Uses (FOSHU)". Retrieved 15 July 2015. 

External links[edit]