Prebiotic Type Spotlight: Fructooligosaccharides (FOS) - Global Prebiotic Association (2024)

Last updated August 2023

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, fructooligosaccharides (FOS) are highlighted.

Overview
FOS is a type of oligosaccharide defined as nondigestible carbohydrates consisting of glucose and fructose sugar molecules connected by β (21) glycosidic bonds and a degree of polymerization that varies from 2 to 60 chain lengths (Kaur et al., 2021; Kherade et al., 2021). FOS is commonly referred to as oligofructose, oligofructan, fructose oligomers, fructans, and glycofructans, and is regularly incorporated into various food applications and wellness products due to its functional properties and extensive health benefits (Kherade et al., 2021). FOS can be found in approximately 36,000 different plants, cereals, and honey; however, these sources only provide trace amounts of FOS, resulting in the need for commercial production (Davani-Davari et al., 2019; Dou et al., 2022; Kherade et al., 2021).

Benefit Areas
FOS was first discovered in 1804 and has been historically used in folk medicine for treating diabetes, constipation, and many other human ailments (Caetano et al., 2016; Kherade et al., 2021). Due to the rise in mass FOS production over the last few decades, scientists have been able to examine this increasingly available prebiotic and the food properties and health benefits it exhibits. Some of these include:

• Stimulating the growth of healthy bacteria such as Bifidobacterium and Lactobacillus (Caetano et al., 2016; Davani-Davari et al., 2019; Kaur et al., 2021; Dou et al., 2022; Mahalak et al., 2023).
• Inhibiting the growth of pathogenic microorganisms such as Clostridium, Salmonella, and Escherichia coli (Caetano et al., 2016; Davani-Davari et al., 2019; Kaur et al., 2021; Dou et al., 2022).
• Supporting gastrointestinal health (Davani-Davari et al., 2019; Kherade et al., 2021).
• Improving mineral absorption (Kaur et al., 2021; Kherade et al., 2021).
• Reducing triglycerides (Caetano et al., 2016; Kaur et al., 2021).
• Supporting healthy glucose metabolism (Caetano et al., 2016).
• Improving immune function (Caetano et al., 2016; Davani-Davari et al., 2019; Kaur et al., 2021).
• Improving atopic dermatitis (Ahn et al., 2023).

Generally, FOS is well tolerated by humans, but some individuals may experience unwanted effects such as stomach discomfort, bloating, flatulence, and diarrhea (Kherade et al., 2021). In addition, when using FOS as a fat or sweetener replacement, the physical and sensory properties of food products should be considered as the taste and texture of foods can be altered (Jackson et al., 2022).

Sources
FOS is a low-molecular-weight version of inulin and can be found naturally in a variety of perennial plants such as artichokes, chicory, onions, leeks, garlic, asparagus, and yacon, as well as cereals and honey (Dou et al., 2022). Yacon is an apple-like herbaceous plant native to the Andean regions of South America that contain the highest concentration of FOS found naturally (Caetano et al., 2016). FOS can be chemically synthesized via glycosidase and glycosyl-transferase, however; this has proven to be a hazardous and costly method of production with a low concentration yield (Davani-Davari et al., 2019). Therefore, the preferred industrial methods of FOS production involve enzymatic synthesis. The first method partially hydrolyzes inulin extracted from chicory using enzymes, resulting in oligofructose (Kherade et al., 2021; Dou et al., 2022). The second method synthesizes sucrose extracted from sugar beet using fungal fructosidases, resulting in short chain FOS (Kherade et al., 2021; Dou et al., 2022). FOS is Generally Recognized As Safe (GRAS) by the United States (US) Food and Drug Administration (FDA) and European Food Safety Authority (EFSA) for use as a general-purpose food ingredient and/or bulking agent in various food categories and infant formulas. EFSA provided a scientific opinion on the substantiation of FOS obtained from chicory inulin as a sugar replacement for food and beverages and concluded that the claimed effect is sufficiently characterized (EFSA, 2014). In Canada, FOS is permitted for use as medicinal and non-medicinal ingredients in Natural Health Products (NHPs) under the Natural Health Products Regulations, in addition to being assessed as a non-novel food by Health Canada’s Food Directorate since FOS has a history of safe use as a food (Health Canada, 2023a; Health Canada, 2023b).

Dose Range
The following dose ranges have been established via clinical trial data and scientific reviews:

• 4 – 15% as a general-purpose food ingredient
• 400 – 680 mg/100 mL in infant formula
• < 500 mg per day as a non-medicinal ingredient in NHPs
• 4 g per day for healthy glucose metabolism
• 4 g per day for reducing triglycerides
• 5 – 15 g per day for supporting gastrointestinal health
• 8 – 15 g per day for supporting immune function
• 5 – 15 g per day for the growth of healthy bacteria

Recent Research
Currently, there are two studies actively recruiting on ClinicalTrials.gov proposing FOS as a prebiotic dietary supplement to evaluate its effect on exercise, the gut microbiome, gastrointestinal and overall human health (ClinicalTrials.gov, 2023). Moreover, searching “fructooligosaccharides” and “oligofructose” retrieved 106 and 13 study results published this year, respectively, highlighting the use of FOS as a fat and sugar replacement and for its beneficial health properties such as gut microbiota, immune function, and others (PubMed, 2023a; PubMed, 2023b). Gonçalves et al. (2023) considered the demand for new food products with reduced sugar and low caloric value and developed a successful and functional prebiotic strawberry preparation for the dairy industry using in situ enzymatic conversion of sucrose into FOS. This study showed that the prebiotic strawberry preparation contained more than 50% (w/w) FOS in total sugars with less than 80% of its original sucrose content and 26-31% less calories. A simulation of the human digestive system showed that more than 90% of FOS would reach the colon intact, validating the prebiotic potential of the strawberry preparation. A study by Mahalak et al. (2023) conducted a 24-hour in vitro experiment that cultured fecal samples of three different adult age groups (25-70 years) to examine the effects of FOS on the gut’s microbiome. The results showed that FOS impacted Bifidobacterium levels in all age groups and that age plays a significant role in the effectiveness of FOS. Another study by Tavares et al. (2023) examined the anti-inflammatory property of a synbiotic containing FOS and Lactobacillus delbrueckii CIDCA 133 on the intestinal mucosal damage induced by chemotherapy in mice. The results of this study revealed that Lactobacillus delbrueckii CIDCA 133 is able to metabolize FOS. A reduction in cellular inflammation was observed, concluding that this synbiotic is a promising treatment for protecting the intestinal mucosa from epithelial damage caused by chemotherapy.

How is FOS used in the marketplace?
FOS is currently being incorporated into various food applications such as formula for infants, baby food, dairy products, meat/fish/poultry products, confectionary/candy, cereal products, beverages, cookies, crackers, bakery products, food supplements, processed foods, etc., throughout the US and Europe. In Canada, FOS has been formulated into foods as well as NHPs for non-medicinal and medicinal purposes such as supporting and maintaining gastrointestinal health, stimulating the growth of healthy bacteria (Bifidobacterium) in the intestine/gut, prebiotic, and many others.

The FOS market is estimated to reach $3.1678 billion USD in 2023 and is projected to grow at a 6% compound annual growth rate (CAGR) to hit $4.9195 billion USD by 2033 (Future Market Insights, 2023). An increased public interest in prebiotic supplementation and healthy food alternatives is a good opportunity to take advantage of the many beneficial properties of FOS, especially in combination with other prebiotics, probiotics, and synbiotics.

Ahn K. (2023). The Effect of Prebiotics on Atopic Dermatitis. Allergy Asthma Immunology Research, 15(3):271-275. https://doi.org/10.4168/aair.2023.15.3.271

Caetano, B.F.R., De Moura, N.A., Almeida, A.P.S., Dias, M.C., Sivieri, K., & Barbisan, L.F. (2016). Yacon (Smallanthus sonchifolius) as a Food Supplement: Health-Promoting Benefits of Fructooligosaccharides. Nutrients, 8(7):436. https://doi.org/10.3390/nu8070436

ClinicalTrials.gov. Retrieved on 2023 Jul 25. Available from: https://clinicaltrials.gov/search?intr=Fructooligosaccharide%20%5C(FOS%5C)&aggFilters=status:rec

Davani-Davari, D., Negahdaripour, M., Karimzadeh, I., Seifan, M., Mohkam, M., Masoumi, S.J., Berenjian, A., & Ghasemi, Y. (2019). Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods, 8(3):92. https://doi.org/10.3390/foods8030092

Dou, Y., Yu, X., Luo, Y., Chen, B., Ma, D., & Zhu, J. (2022). Effect of Fructooligosaccharides Supplementation on the Gut Microbiota in Human: A Systematic Review and Meta-Analysis. Nutrients, 14(16):3298. https://doi.org/10.3390/nu14163298

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies). (2014). Scientific Opinion

on the substantiation of a health claim related to non-digestible carbohydrates and reduction of post-prandial glycaemic responses pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA Journal, 12(1):3513. https://doi.org/10.2903/j.efsa.2014.3513

Future Market Insights. Fructo-Oligosaccharides Market Outlook (2023 to 2033). Retrieved on 2023 Jul 26. Available from: https://www.futuremarketinsights.com/reports/fructo-oligosaccharides-market

Gonçalves, D.A., Alves, V.D., Teixeira, J.A., & Nobre, C. (2023). Development of a functional prebiotic strawberry preparation by in situ enzymatic conversion of sucrose into fructo-oligosaccharides. Food Research International, 168(112671). https://doi.org/10.1016/j.foodres.2023.112671

Health Canada a. NHPID: Fructooligosaccharides. Retrieved on 2023 Jul 26. Available from: https://webprod.hc-sc.gc.ca/nhpid-bdipsn/ingredReq.do?id=3646&lang=en

Health Canada b. List of non-novel determinations for food and food ingredients. Retrieved on 2023 Jul 26. Available from: https://www.canada.ca/en/health-canada/services/food-nutrition/genetically-modified-foods-other-novel-foods/requesting-novelty-determination/list-non-novel-determinations.html#wb-auto-4

Jackson, P.P.J., Wijeyesekera, A., & Rastall, R.A. (2022). Inulin-type fructans and short-chain fructooligosaccharides–their role within the food industry as fat and sugar replacers and texture modifiers–what needs to be considered! Food Science & Nutrition, 11:17-38. https://doi.org/10.1002/fsn3.3040

Kaur, A.P., Bhardwaj, S., Dhanjal, D.S., Nepovimova, E., Cruz-Martins, N., Kuča, K., Chopra, C., Singh, R., Kumar, H., Șen, F., Kumar, V., Verma, R., & Kumar, D. (2021). Plant Prebiotics and Their Role in the Amelioration of Diseases. Biomolecules, 11(3):440. https://doi.org/10.3390/biom11030440

Kherade, M., Solanke, S., Tawar, M. & Wankhede, S. (2021). Fructooligosaccharides: A comprehensive review. Journal of Ayurvedic and Herbal Medicine, 7(3):193-200.

Mahalak, K.K., Firrman, J., Narrowe, A.B., Hu, W., Jones, S.M., Bittinger, K., Moustafa, A.M., & Liu L. (2023). Fructooligosaccharides (FOS) differentially modifies the in vitro gut microbiota in an age-dependent manner. Frontiers in Nutrition, 9:1058910. https://doi.org/10.3389/fnut.2022.1058910

PubMed a. Fructooligosaccharides. Retrieved on 2023 Jul 25. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=fructooligosaccharides&filter=years.2023-2023

PubMed b. Oligofructose. Retrieved on 2023 Jul 25. Available from:

https://pubmed.ncbi.nlm.nih.gov/?term=oligofructose&filter=years.2023-2023

Tavares, L.M., de Jesus, L.C.L., Batista, V.L. Barroso, F.A.L., dos Santos Freitas, A., Campos, G.M., Américo, M.F., da Silva, T.F., Coelho-Rocha, N.D., Belo, G.A., Drumond, M.M., Mancha-Agresti, P., Vital, K.D., Fernandes, S.O.A., Cardoso, V.N., Birbrair, A., Ferreira, E., Martins, F.S., Laguna, J.G., & Azevedo, V. (2023). Synergistic synbiotic containing fructooligosaccharides and Lactobacillus delbrueckii CIDCA 133 alleviates chemotherapy-induced intestinal mucositis in mice. World Journal of Microbiology and Biotechnology, 39:235. https://doi.org/10.1007/s11274-023-03679-0