Prebiotics

What is it used for?

Refer to Tables 2.1 to 2.3 below.

What this guide covers

Prebiotics are defined by their ability to selectively feed beneficial gut microbiota to confer a health benefit, not by being a fibre itself. It is important to note that some prebiotics are not fibres. i.e., Not all prebiotics contain fibre and not all fibres are prebiotics.

• this reference may be used to support single ingredient products or multi-ingredient products containing a active ingredient from Table 1. Combination restrictions are described in the ‘Combination rules' section.

• this reference is intended to support prebiotic claims for the listed active ingredients under specified conditions of use. Certain listed ingredients may also be eligible for fibre-content claims, where applicable. Prebiotic and fibre-content claims are distinct concepts and are assessed independently. Not all fibres qualify as prebiotics, and a fibre-content claim must not be represented or implied as a prebiotic effect (and vice versa).

• Refer to Appendix I for the definitions of prebiotics, both internationally and domestically, and for the additional considerations applied by the source authority when establishing evidence requirements.

Restrictions when this reference is combined with other references (source review category II and III):

The following combinations are not acceptable as source review category II. These products may be submitted as a source review category III with supporting evidence.

• Inulin and/or FOS - with invertase

• GOS - with lactase or alpha-galactosidase

• XOS - with hemicellulase or xylanase

• 2'-Fucosyllactose and/or Lacto-N-neotetraose - with lactase

• Acacia gum - with any digestive enzymes

Who does this guide cover?

Adults 18 years and older

How is it taken?

Oral

Which forms are covered?

this reference excludes foods or food-like dosage forms as indicated in the Compendium of references Guidance Document.

Quantities

¹References consulted for the uses or purposes: Lee et al. 2024; Looijesteijn et al. 2024; Van Harsselaar et al. 2024; Jackson et al. 2023; Parker et al. 2023; Wilson et al. 2021; Vulevic et al. 2018; Hong et al. 2017; Elison et al. 2016; Ramnani et al. 2015; Finegold et al. 2014; Holscher et al. 2014; Xiao et al. 2012; Marteau et al. 2011; Ramnani 2010; Calame et al. 2009; Silk et al. 2009; Na and Kim 2007; Roberfroid 2007a,b; Bouhnik et al. 2006; IOM 2005; Bouhnik et al. 2004; Cherbut et al. 2003; Menne et al. 2000; Bouhnik et al. 1999; Iino et al. 1997; Gibson et al. 1995; Tamai et al. 1992. ²References consulted for the doses: Lee et al. 2024; Looijesteijn et al. 2024; Van Harsselaar et al. 2024; Jackson et al. 2023; Parker et al. 2023; Jarrar et al. 2021; Wilson et al. 2021; Kaddam et al. 2019; Vulevic et al. 2018; Babiker et al. 2017; Hong et al. 2017; Elison et al. 2016; Hernandez-Gonzalez et al. 2016; Ramnani et al. 2015; Childs et al. 2014; Finegold et al. 2014; Holscher et al. 2014; Xiao et al. 2012; Calame et al. 2009; Glover et al. 2009; Silk et al. 2009; Kolida and Gibson 2007; Kolida et al. 2007; Na and Kim 2007; Bouhnik et al. 2006; IOM 2005; Bouhnik et al. 2004; Cherbut et al. 2003; Menne et al. 2000; Bouhnik et al. 1999; Coussement 1999; Iino et al. 1997; Tamai et al. 1992. ³For products containing 2'-fucosyllactose (2'-FL) in combination with lacto-N-neotetraose (LNnt), the prebiotic/growth of healthy bacteria uses or purposes are supported only when the combined daily intake of 2'-FL and LNnt is 10-20 grams and the 2'-FL:LNnt ratio is between 2:1 and 4:1 [Source note 1].

How is it used?

All products except those containing 2'-Fucosyllactose alone or in combination with Lacto-N-neotetraose

• Take with at least 250 mL of liquid [Source note 3].

• Maintain adequate fluid intake [Source note 4].

• Take a few hours before or after taking other medications or health products [Source note 5].

Powder dosage forms

• (Thoroughly) Mix product in at least 250 mL of liquid immediately before consumption [Source note 6].

• Maintain adequate fluid intake [Source note 7].

• Take a few hours before or after taking other medications or health products [Source note 8].

Products containing inulin or fructooligosaccharides (FOS) (optional)

To minimize gastrointestinal side effects, take in divided doses with meals [Source note 9].

Products containing inulin, fructooligosaccharides (FOS) or Short-chain fructooligosaccharides (scFOS) for constipation/irregularity

Start at a lower dose and increase gradually to the recommended daily dose or until the desired effect is obtained.

How long is it used?

Products providing more than 10 g acacia, per day

Ask a healthcare professional for use beyond 12 weeks [Source note 10].

Products providing up to 4 g xylooligosaccharides (XOS), per day

Ask a healthcare professional for use beyond 8 weeks [Source note 11].

Products providing more than 4 g xylooligosaccharides (XOS), per day

Ask a healthcare professional for use beyond 3 weeks [Source note 12].

Warnings and precautions

Products containing inulin for constipation/irregularity

Ask a healthcare professional if symptoms persist or worsen.

When should it be avoided?

Products containing inulin for constipation and/or irregularity

Do not use if you have fever or any undiagnosed gastrointestinal trouble [Source note 13].

Possible side effects

Products containing inulin, fructooligosaccharides (FOS), or transgalactooligosaccharides (GOS)

Stop use if hypersensitivity/allergy occurs [Source note 14].

Products providing 5 g or more inulin, fructooligosaccharides (FOS) or short-chain fructooligosaccharides (scFOS) per day

When using this product you may experience temporary gas and bloating (Mysonhimer and Hoslcher 2022; Ramnani et al. 2015, 2010; Schaafsma and Slavin 2015; Holsher et al. 2014; Marteau et al. 2011; Bonnema et al. 2010; Bruhwyler et al. 2009; Bouhnik et al. 2007, 2006; Kolida and Gibson 2007; Menne et al.p2000; Coussement 1999).

Storage

Must be established in accordance with the requirements described in the applicable product regulations.

Optional

Store in a cool, dry place. Keep tightly closed.

Conditions for combined preparations

• The total amount of a combination of 2 or more active ingredients from Table 1 must not exceed 15 g per day and the amount of the active ingredient XOS must not exceed 8 g per day.

• The claims listed in Table 2.2. can be supported by a combination of the supporting active ingredients if the total amount meets a minimum of 2 g per day. Note that only 80% of the daily dose of acacia gum should be included in the calculation.

Fibre-related claims

¹References consulted for the uses or purposes: HC 2025; CNF 2024; FCC 2024; Calame et al. 2009; IOM 2005; Cherbut et al. 2003. ²References consulted for the doses: HC 2025; CNF 2024; Jarrar et al. 2021; Kaddam et al. 2019; Babiker et al. 2017; Canfora et al. 2017; Childs et al. 2014; Calame et al. 2009; Glover et al. 2009; IOM 2005; Cherbut et al. 2003; Menne et al. 2000; Coussement 1999. ³The claim “source of fibre” may be further qualified on the label, as applicable. Products providing at least 4 grams of fibre per day may use the additional qualifier “High source of fibre” on the label, while products providing at least 6 grams of fibre per day may use “Very high source of fibre”. These thresholds were adapted from source authority's food labelling approach and applied within the NHP framework, where products are evaluated based on the recommended daily dose [Source note 2]. ⁴The minimum dose of acacia was adjusted to 2.5 g as acacia contains around 80% fibre (2.5 g of acacia would provide 2 g of fibre).

¹References consulted for the use or purpose and doses: Watson et al. 2019; Buddington et al. 2017; Micka et al. 2017; Meksawan et al. 2016; Holscher et al. 2014; Marteau et al. 2011; Yen et al. 2011; IOM 2005; Chen et al. 2000.

• The claims from Table 2.1. can be combined on the product label (e.g., A source of prebiotic which helps stimulate the growth of healthy bacteria (such as bifidobacteria) in the intestine).

• The claims from Table 2.2. and 2.3 can also be combined; however, it is recommended to keep claims from Table 2.1 separate from the other claims on the label to avoid any misinterpretation or implied links between the effects.

• The terms 'Helps' or 'Helps to' can be used interchangeably on the label.

APPENDIX I - INTERNATIONAL AND DOMESTIC PREBIOTIC DEFINITIONS AND CONSIDERATIONS

Various definitions and considerations for prebiotics are available in the scientific and regulatory literature. The following is provided as background for future refinement of the product class's definition and regulation in Canada.

The International Scientific Association for Probiotics and Prebiotics (ISAPP) prebiotic definition is described as follows:

• “A substrate that is selectively utilized by host microorganisms conferring a health benefit”. [Source note 16]

The ISAPP definition has also been adopted by the International Probiotics Association [Source note 17], which has published a narrative scientific review on prebiotic history, challenges, and proposed standards [Source note 18]. Notably and importantly, this includes five recommendations for prebiotic characteristics:

• “The first characteristic is that the prebiotic compound should be resistant to digestion by the host; a prebiotic must reach the sipe of action intact.”

• “The second characteristic for a prebiotic is that they should not be absorbed within the GI tract, so that they will remain available for selective utilisation by the gastrointestinal microbes.“

• “The third characteristic for a prebiotic relates to its fermentability, and the fourth (related) characteristic implies that microbial fermentation must be selective.”

• “The last characteristic requires that the product must have positive physiological effects, i.e. a prebiotic compound must be delivered in a sufficient/appropriate dose to elicit a physiological benefit (i.e. promote health).” [Source note 19]

For clarity, the source authority recommends the ISAPP definition and IPA characterization of prebiotics be followed. The source authority intends to uphold the notions of selectivity (i.e., increasing beneficial bacterial levels with limited/no growth of problematic/pathogenic bacteria) and beneficial physiological effects (based on human clinical evidence) in all prebiotic products.

However, the source authority's approach to evidence requirements is also risk-based as outlined in the Pathway for Licensing supplements Making Modern Health Claims guidance document. This approach means that low-risk prebiotic products do have a specific set of minimum requirements that would potentially not meet ISAPP's defined criteria of controlled, well-conducted trials. Medium- and high-risk prebiotic product use scenario evidence requirements are considered to align with the ISAPP definition's criteria and the IPA characterization requirements, however.

The source authority's approach to low-risk minimum evidence requirements for prebiotics includes corroborated preliminary scientific findings (e.g. two pilot or open-label well conducted human clinical trials). This amounts to a scientific likelihood of effect that is derived from small sample sizes and potentially uncontrolled data. Under low-risk requirements and based on the accumulated evidence, a significant beneficial shift to the microbiota composition is considered to be consistent with general physiological benefits inherent to a prebiotic compound's effects. This includes helping support and maintain a healthy digestive system (e.g., microbiota utilization of the prebiotic leads to fermentation and production of metabolites that are known to influence gut function by supporting normal bowel movements and promoting a favourable gut environment).

Overall, this means that demonstration of a significant and selective beneficial shift to the microbiota composition can be considered sufficient evidence of a beneficial physiological effect in low-risk scenarios for claims such as ‘Source of Prebiotics' (e.g., supported by human clinical evidence from two pilot studies or open-label well conducted human clinical trials). These minimum evidence requirements were obligatorily applied in the creation of this reference as the ingredients and prebiotic claims are considered low-risk as per the Pathway for Licensing supplements Making Modern Health Claims guidance document.

Considering the difference between source authority's low-risk minimum requirements and ISAPP's criteria, it is also recognized that the term “prebiotic” is used variably across the global marketplace and the scientific literature. Some publications, such as that from the Global Prebiotic Association [Source note 20], use broader definitions that don't put as much weight on “selectivity” as the ISAPP definition does. While source authority does not currently apply these broader definitions, they are considered indicative of a need for continued discussion.

Given this, the source authority re-iterates that it currently intends to follow the ISAPP definition of a prebiotic as best possible, including within the limitations of pre-existing source guidance for low-risk products. The source authority will continue to monitor the literature for future developments.