Prebiotic Type Spotlight: Tagatose
Last Updated October 2024
Each edition of GPA’s Prebiotic Spotlight focuses on a specific prebiotic type to raise awareness around the prebiotic itself, its sources, any notable and/or recent research, and how it is used in the marketplace. In this issue, tagatose is highlighted.
Overview
Tagatose is a naturally occurring monosaccharide having sweetness 90% that of sucrose (Roy et al., 2018). Tagatose is a stereoisomer of fructose, only differing at the fourth carbon atom, and is naturally found in a variety of fruits and dairy products. Tagatose can be produced for the commercial market using lactose, fructose or maltodextrin as feedstocks as well as by enzymatic conversion of starches (Bertelsen et al., 1999; Food Safety Authority Ireland, 2017; Bonumose LLC, 2020). Tagatose is a bulk sweetener with no odor or off-flavors. It is a white crystalline powder that takes part in the Maillard reaction, which leads to the browning of food. Only 15-20% of D-tagatose is absorbed in the small intestine, leaving the remaining 80-85% of ingested D-tagatose to be fermented in the colon by indigenous microflora, leading to various prebiotic effects and a reduced caloric value compared to traditional sugars (Bertelsen et al., 1999). In-vitro studies have demonstrated that tagatose as a synbiotic substrate enhances the growth of Lactobacillus casei 01 and Lactobacillus rhamnosus strain GG, reinforcing the attachment on epithelial cells, and therefore enhancing cholesterol-lowering activities (Koh et al., 2013).
Benefit Areas
In 1988 tagatose was developed as a low caloric sugar and introduced commercially as a bulk sweetener in 1992 (Roy et al., 2018). Since then, research of tagatose has demonstrated many health benefits, which include:
- Tagatose inhibits the growth of oral pathogens in Streptococci mutans and Streptococci gordonii, while the commensal Streptococci oralis is negligibly affected, and therefore associated with good oral hygiene in the saliva metabolome of healthy volunteers (Mayumi et al., 2021).
- Consumption of tagatose may lead to increased production of butyrate and an increase of lactobacilli, without any gastrointestinal complaints in healthy men and women (Venema et al., 2004).
- Supplementation with tagatose led to increased bacterial density and short chain fatty acid (SCFA) production, specifically butyrate in healthy adults and propionate in adults with type 2 diabetes (T2D) (Van den Abbeele et al., 2023).
- Tagatose supplemented gum may help prevent dental caries, periodontitis, and oral diseases in healthy adults (Nagamine et al., 2020).
- Tagatose supplementation resulted in lowered fasting blood glucose, HbA1c, LDL, and total cholesterol in T2D patients (Ensor et al., 2015).
- Consuming tagatose significantly blunts the rise in plasma glucose levels after oral glucose intake in patients with diabetes mellitus, without significantly affecting insulin level (Donner et al., 1999).
- Tagatose containing drinks significantly reduced insulin and C-peptide levels in healthy adults (Kwak et al., 2013).
- A preload of a mixture of tagatose and isomalt resulted in slower gastric emptying in healthy adults compared to a preload of sucralose (Wu et al., 2012)
Sources
Tagatose is found in trace quantities in various natural foods, including sterilized powdered milk, hot cocoa, cheese, yogurts, and other dairy products. Tagatose can be produced through a combination of chemical and enzymatic processes. Lactose can be enzymatically split into glucose and galactose. Then, galactose reacts with a metal hydroxide (isomerization), forming an insoluble tagatose complex in the presence of a catalyst (calcium chloride or sodium chloride). Next, the tagatose is neutralized with an acid to form an insoluble salt and thereafter the tagatose is separated from the salt by simple filtration (Roy et al., 2018). Enzymes can also be used to convert either fructose or maltodextrin directly to tagatose, without the need for chemical catalysts (Food Safety Authority Ireland, 2017; Bonumose LLC, 2020). Additionally, biological transformation may be achieved by reduction of psicose to talitol, and subsequent oxidation of talitol to tagatose, by enzymatic action of Mucoraceae fungi. Tagatose has been accepted as a humectant, stabilizing agent, and sweetening agent permitted for use and included in Health Canada’s Natural Health Products Ingredients Database. Tagatose derived from maltodextrin is also approved in Canada as a novel food. In 2011, the European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition and Allergies (NDA) issued a scientific opinion on the substantiation of health claims related to sugar replacers including tagatose, and maintenance of tooth mineralization by decreasing tooth demineralization and reduction of post-prandial glycemic responses. The United States (US) Food and Drug Administration (FDA) has affirmed tagatose as Generally Recognized as Safe (GRAS) since 2001, thereby permitting its use as a sweetener in foods and beverages. US FDA has authorized a health claim for tagatose supporting its role in reduction of dental caries.
Dose Range
The Joint Expert Committee on Food Additives (JECFA) has removed an acceptable daily intake level from tagatose because of its demonstrated safety (JECFA, 2006).
Gastrointestinal symptoms such as bloating, belching, flatulence, and laxation may be experienced by excessive consumption of over 30 g/serving of products containing tagatose. These symptoms are characterized as mild, transient, and not experienced by all consumers, and therefore do not pose a significant health or safety concern. Additionally, the EFSA has affirmed that doses over or equal to 7.5 g/meal help to balance blood glucose levels.
Recent Research
Currently, there are five studies registered on ClinicalTrials.gov studying the effects of tagatose on glycemic control and postprandial response, appetite, and energy intake (ClinicalTrials.gov, 2024). Moreover, searching of “tagatose” on PubMed retrieved 25 studies published in 2024, ranging from human clinical trials on the effects of tagatose in the oral microbiome, to food chemistry studies examining methods of producing tagatose.
An animal study conducted by Shi et al. (2024) utilized male C57BL/6 mice to investigate the effects of tagatose on chemically induced colitis. Tagatose was administered to mice daily at dosages of either 150 mg/kg or 300 mg/kg for 10 weeks, while glucose was administered to wildtype mice as a control. To assess the potential of tagatose to inhibit the progression of colon cancer associated with colitis, azoxymethane and dextran sulphate sodium (AOM + DSS) were administered to mice that previously had received tagatose to induce carcinogenesis. The study found an association between the severity of inflammatory bowel disease, occurrence of colorectal cancer, and reduced levels of blood tagatose. Tagatose overall demonstrated an ability to protect against colitis. The suggested mechanism of action is that tagatose may safeguard integrity of lysosomes, hence restricting the release of cathepsin B, preventing mitochondrial dysfunction and the breakdown of tight junctions. Therefore, tagatose may result in increased serum albumin, ZO-1/Claudin-1/Occludin, and bodyweight, and subsequently decreased inflammation. Clinical studies are warranted to confirm the protective effect of tagatose on colitis and the intestinal epithelial barrier in humans.
A randomized clinical exploratory pilot study by Zakis et al. (2024) evaluated the modulating effects of five commonly used sweeteners, including tagatose, on the oral microbiome. This study recruited 65 healthy adults (18-55 years of age) with no oral conditions including overt dental caries, use of dentures, or any apparent oral lesions. Participants were allocated to use mouth rinses containing test sweetener solutions (10%) in water of either inulin (n=14), isomaltulose (n=14), glucose (n=12), tagatose (n=13) or trehalose (n=12), used three times per day for 2 weeks. Specifically, participants were instructed to draw 10 ml of mouth rinse, rinse in mouth for 30 seconds, spit it out, and repeat. The microbiota composition of supragingival dental plaque and the tongue dorsum coating were analyzed by 16S RNA gene amplicon sequencing. Dental plaque red fluorescence and salivary pH were also measured. The study found that the effects on the oral microbiome were sweetener dependent, with the most pronounced effects on plaque microbiota. Tagatose mouth rinses specifically led to a minor compositional shift in plaque, however, this was to a lower effect than other sweetener mouth rinses. Further research into the effects of tagatose on subgingival microbiome composition may provide valuable insights into the potential use of tagatose for the oral microbiome.
A literature review by de Cassia Ortiz et al. (2024) highlights studies completed in recent years that demonstrate the effects of tagatose on the oral microbiome, and other use cases. In summary, evidence suggests that tagatose has antioxidant and prebiotic effects, low digestibility, reduced glycemic and insulinemic responses, and has the potential to improve lipid profile. Antioxidant properties of tagatose favour the limitation of free radicals and reduction of cellular oxidative stress. Many findings have suggested tagatose to be an effective antibacterial for specific oral species. Tagatose reversed bacterial coaggregations, including periodontopathogen species, and impaired the activity and growth of a cariogenic bacteria, S. mutans. Additionally, tagatose inhibits biofilm formation, pH decrease, and insoluble glucan synthesis in S. mutans. The literature review indicates tagatose may contribute to the prevention of systemic diseases and is a promising agent to improve oral health.
How is tagatose used in the marketplace?
Tagatose can mimic the sweetness and functional attributes of traditional sugars while also presenting consumers with demonstrated gut and metabolic health benefits. The tagatose market was valued at $161.2 million USD in 2023 and is expected to have a compound annual growth rate (CAGR) of over 4.7% between 2024 and 2032 (Global Market Insights, 2024). Tagatose has the potential to replace sugar as its sweetness and taste quality is like that of sucrose (Roy et al., 2018). Increasing consumer awareness of sugars health implications drives a demand for low calories sweeteners like tagatose. Tagatose is naturally sourced, and has a low blood sugar impact, making it a desirable alternative to sugar. The main market sector for tagatose applications is in food and beverage products, where it can be used in both hot and cold foods and beverages due to its stability and solubility. Other market sectors for tagatose include pharmaceuticals, personal care products, and animal feed.
References
Bertelsen, H., Jensen, BB., & Buemann, B. (1999). D-tagatose- a novel low-calorie bulk sweetener with prebiotic properties. World review of nutrition and dietetics, 85:98-109. https://doi.org/10.1159/isbn.978-3-318-00483-0
Bonumose, LLC. (2020). GRAS notice no. 977 for d-tagatose produced via novel enzymatic cascade. Available from: https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=977
ClinicalTrials.gov. Tagatose. Retrieved on 2024 Oct 01. Available from: https://clinicaltrials.gov/search?intr=Tagatose
de Cassia Ortiz, A., Fideles, SOM., Reis, CHB., Pagani, BT., Bueno, LMM., Moscatel, MBM., Buchaim, RL., & Buchaim, DV. (2024). D-tagatose: a rare sugar with functional properties and antimicrobial potential against oral species. Nutrients, 16(12):1943. https://doi.org/10.3390/nu16121943
Donner, TW., Wilber, JF., & Ostrowski, D. (1999). D-tagatose, a novel hexose: acute effects on carbohydrate tolerance in subjects with and without type 2 diabetes. Diabetes, obesity & metabolism, 1(5):285-291. https://doi.org/10.1046/j.1463-1326
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2011). Scientific Opinion on the substantiation of health claims related to sugar replacers xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt, erythritol, D-tagatose, isomaltulose, sucralose and polydextrose and maintenance of tooth mineralisation by decreasing tooth demineralisation (ID 463, 464, 563, 618, 1182, 1591, 2907, 2921, 4300), and reduction of post-prandial glycaemic responses (ID 617, 619, 669, 1590, 1762, 2903, 2908, 2920) pursuant to Article 13(1) of regulation (EC) No 1924/2006. EFSA Journal, 9(4):2076. https://doi.org/10.2903/j.efsa.2011.2076
Ensor, M., Banfield, AB., Smith, RR., Williams, J., & Lodder, RA. (2015). Safety and efficacy of d-tagatose in glycemic control in subjects with type 2 diabetes. J endocrinol diabetes obese, 3(1): 1065. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820068/
Food Safety Authority of Ireland (2017). Substantial equivalence opinion d-tagatose. Available from: https://www.fsai.ie/getattachment/b356c06d-23b0-45be-b191-0fe5355210cc/2017-substantial-equivalence-opinion-d-tagatose.pdf?lang=en-IE
Global Market Insights. Tagatose Market Size – By Type (L-Tagatose, D-tagatose) Application (Food & beverages, Pharmaceuticals, Personal care, Animal feed, Others) Distribution Channel (Online retail, Specialty store, Direct sales) & Forecast, 2024-2032. Retrieved on 2024 Sep 30. Available from: https://www.gminsights.com/industry-analysis/tagatose-market
Health Canada, Natural Health Products Ingredients Database (2024). Chemical Substance -D -Tagatose. Retrieved on 2024 Oct o3. Available from: https://webprod.hc-sc.gc.ca/nhpid-bdipsn/ingredReq?id=961Joint FAO/WHO Expert Committee on Food Additives (JECFA). (2006). Safety evaluation of certain food additives. WHO food additives series, 54:145-148. http://whqlibdoc.who.int/publications/2006/9241660546_eng.pdf.
Koh, JH., Choi, SH., Park, SW., Choi, NJ., Kim, Y., & Kim, SH. (2013). Synbiotic impact of tagatose on viability of Lactobacillus rhamnosus strain GG mediated by the phosphotransferase system (PTS). Food microbiology, 36(1):7-13. https://doi.org/10.1016/j.fm.2013.03.003
Kwak, JH., Kim, MS., Lee, JH., Yang, YJ., Lee, KH., Kim, OY., & Lee, JH. (2013). Beneficial effect of tagatose consumption on postprandial hyperglycemia in Koreans: a double-blind crossover designed study. Food function, 4(8):1223-1228. https://doi.org/10.1039/C3FO00006K
Mayumi, S., Kuboniwa, M., Sakanaka, A., Hashino, E., Ishikawa, A., Ijima, Y., & Amano, A. (2021). Potential of prebiotic d-tagatose for prevention of oral disease. Frontiers in cellular and infection microbiology, 11:767944. https://doi.org/10.3389/fcimb.2021.767944
Nagamine, Y., Hasibul, K., Ogawa, T., Tada, A., Kamitori, K., Hossain, A., Yamaguchi, F., Tokuda, M., Kuwahara, T., & Miyake, M. (2020). D-tagatose effectively reduces the number of Streptococcus mutans and oral bacteria in healthy adults subjects: a chewing gum pilot study and randomized clinical trial. Acta medica Okayama, 74(4):307-317. http://doi.org/10.18926/AMO/60369
PubMed. Tagatose. Retrieved on 2024 Oct 01. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=tagatose&filter=years.2024-2024&timeline=expanded
Roy, S., Chikkerur, J., Roy, SC., Dhali, A., Kolte, AP., Sridhar, M., & Samanta, AK. (2018). Tagatose as a potential nutraceutical: production, properties, biological roles, and applications. Journal of food science, 83(11):2699-2709. https://doi.org/10.1111/1750-3841.14358
Shi, F., Gao, YS., Han, SM., Shi, H., Hou, QS., Gao, Y., Wen, XW., Zhu, ZY., Liu, K., Gong, WP., Wang, BS., Liu, X., & Zou, L. (2024). Targeting MLCK-MLC2 signaling pathway by tagatose alleviates dysregulated mitochondria-associated colonitis. Journal of functional foods, 117:106222. https://doi.org/10.1016/j.jff.2024.106222
US FDA (2011). Tagatose GRAS notice. Retrieved on 2024 Oct 03. Available from: https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=352&sort=GRN_No&order=DESC&startrow=1&type=basic&search=d%2Dtagatose
Van den Abbeele, P., Poppe, J., Deyaert, S., Laurie, I., Gravert, TKO., Abrahamsson, A., Baudot, A., Karnik, K., & Risso, D. (2023). Low-no-calorie sweeteners exert marked compound-specific impact on the human gut microbiota ex vivo. International journal of food sciences and nutrition, 74(5):630-644. https://doi.org/10.1080/09637486.2023.2240037
Venema, K., Vermunt, SH., & Brink, EJ. (2005). D-tagatose increases butyrate production by the colonic microbiota in healthy men and women. Microbial ecology in health and disease, 17(1):47-57. https://doi.org/10.1080/08910600510035093
Wu, T., Zhao, BR., Bound, MJ., Checklin, HL., Bellon, M., Little, TJ., Young, RL., Jones, KL., Horowitz, M., & Rayner, CK. (2012). Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans. American journal of nutrition, 95(1):78-83. https://doi.org/10.3945/ajcn.111.021543
Zakis, DR., Brandt, BW., van der Waal, SV., Keijser, BJ., Crielaard, W., van der Plas, DWK., Volgenant, CMC., & Zaura, E. (2024). The effect of different sweeteners on the oral microbiome: a randomized clinical exploratory pilot study. Journal of oral microbiology, 16(1):2369350. https://doi.org/10.1080/20002297.2024.2369350