Cognitive Function Products

Date

February 28, 2025

Proper name(s), Common name(s), Source information

References: Proper names: NHPID 2023; Common names: NHPID 2023; Source information: EMA 2008; Bone 2003; Hoffman 2003; Lemaire and Adosraku 2002; API 2001; Bradley 1992; Williamson et al. 1988; BHP 1983; Fellows and Bell 1970; Remington and Wood 1918; BPC 1911.

¹Do not use the fresh plant (Bone 2003; Hoffman 2003; Bradley 1992; BHP 1983).

²Isolate. The source information for L-5-Hydroxytryptophan can also be synthetic.

References: Proper names: NHPID 2023; Common names: NHPID 2023; Source information: Hoffman 2003; Williamson et al. 1988.

References: Proper names: NHPID 2023; Common names: NHPID 2023; Source information: NHPID 2023; Yurko-Mauro et al. 2010; Calabrese et al. 2008; Bone 2003; De Jesus Moreno Moreno 2003; API 2001; Parnetti et al. 2001; Barbagallo et al. 1994; Parnetti et al. 1993; Canal et al. 1991.

¹Synthetic

²Isolate

³For cod liver oil and fish oil, the species common name can be listed as source information on the label instead of the organism group. Fish oil corresponds to oil from the whole body of one or more of species of the families listed in the table in its natural and/or concentrated triglyceride/triacylglycerol form and/or its concentrated esterified form.

References: Proper names: NHPID 2023; Common names: NHPID 2023; Source information: EMA 2013; ESCOP 2009; Bradley 2006; Kennedy et al. 2004; Taylor 2003; Barnes et al. 2002; BHP 1983.

¹Synthetic

²If caffeine is sourced from Camellia sinensis, Coffea arabica, Coffea canephora, Cola acuminata, Ilex paraguariensis, Ilex guayusa, Paullinia cupana or Theobroma cacao , it must be isolated and purified. Extracts of Ilex paraguariensis and Paullinia cupana must be represented separately. This monograph does not support extracts of Camellia sinensis, Coffea arabica, Coffea canephora, Cola acuminata, Ilex guayusa or Theobroma cacao .

References: Proper names: NHPID 2023; Common names: NHPID 2023; Source information: Kanehira et al. 2011; Abdou et al. 2006; Yamakoshi et al. 2006.

¹Synthetic

²Isolate

References: Proper names: NHPID 2023; Common names: NHPID 2023; Source information: Upton 2012; Winston and Kuhn 2008; Winston and Maimes 2007; WHO 2004; Bone 2003; Hoffman 2003; Thomsen 2002; Williamson 2002; API 2001; Blumenthal et al. 2000; Upton 1999; WHO 1999; Bradley 1992; BHP 1983.

References: Proper names: NHPID 2023; Common names: NHPID 2023; Source information: NHPID 2023; DNP 2017; Martinez-Pinilla et al. 2015; Ma et al. 2007; Kihlman 1977.

¹Synthetic

²Isolate

Route of Administration

Oral

Dosage Form(s)

This monograph excludes foods or food-like dosage forms as indicated in the Compendium of Monographs Guidance Document.

Acceptable dosage forms for oral use are indicated in the dosage form drop-down list of the web-based Product Licence Application form for Compendial applications.

Use(s) or Purpose(s)

Refer to Tables 2.1 to 2.6. below.

Notes:

• The recommended uses can be combined on the product label if from the same traditional or non-traditional system of medicine.
• The terms 'Helps' or 'Helps to' can be used interchangeably on the label.

Dose(s)

Subpopulation(s)

Adults 18 years and older

Quantity(ies)

Refer to Tables 2.1 to 2.7. below.

Note: Methods of preparation: Solvents allowed for the methods of preparation, Non-Standardized Extracts “Dry extract” and Non-Standardized Ethanolic Extracts “Dry extract” as part of this monograph are ethanol and/or water only, unless otherwise specified. For Non-Standardized Aqueous Extracts “Dry extract”, water is the only solvent allowed.

¹References consulted for the uses or purposes: Sutanto et al. 2024; ESCOP 2009; Bradley 2006; Bone 2003; Hoffman 2003; Barnes et al. 2002; Kapoor 2001; Blumenthal et al. 2000; Upton 2000; Wheatley 1999; Poldinger et al. 1991; Williamson et al. 1988; Ellingwood 1983; Felter and Lloyd 1983; Soulairac and Lambinet 1977; Grieve 1971.

²References consulted for the doses: Sutanto et al. 2024; CNF 2023; EMA 2008; Anghelescu et al. 2006; Bone 2003; Hoffman 2003; API 2001; Kapoor 2001; Blumenthal et al. 2000; Bradley 1992; Williamson et al. 1988; BHP 1983; Ellingwood 1983; Felter and Lloyd 1983; Soulairac and Lambinet 1977; Remington and Wood 1918; BPC 1911.

¹References consulted for the uses or purposes: Williamson et al. 1988; refer to respective single ingredient monographs.

²References consulted for the doses: Williamson et al. 1988; refer to respective single ingredient monographs.

³Note: For Valerian extracts standardized to valerenic acid or sesquiterpenic acids, the quantity dried equivalent and the extract ratio must be provided.

¹References consulted for the uses or purposes: Nakazaki et al. 2021; McGlade et al. 2015, 2012; Morgan and Stevens 2010; Yurko-Mauro et al. 2010; Barbhaiya et al. 2008; Calabrese et al. 2008; Malaguanera et al. 2008; Stough et al. 2008; Raghav et al. 2006; Murthy 2004; De Jesus Moreno Moreno 2003; Roodenrys et al. 2002; API 2001; Parnetti et al. 2001; Stough et al. 2001; Thal et al. 2000; Upton 2000; Neri et al. 1995; Barbagallo et al. 1994; Pettegrewet al. 1994; Parnetti et al. 1993; Sano et al. 1992; Canal et al. 1991; Spagnoli et al. 1991.

²References consulted for the doses : Nakazaki et al. 2021; McGlade et al. 2015, 2012; Cotroneo et al. 2013; EFSA 2013; Jensen et al. 2010; Morgan and Stevens 2010; Quinn et al. 2010; Yurko-Mauro et al. 2010; Calabrese et al. 2008; Malaguanera et al. 2008; Mahoney et al. 2007; Bone 2003; De Jesus Moreno Moreno 2003; API 2001; Kapoor 2001; Parnetti et al. 2001; Stough et al. 2001; Thal et al. 2000; Barbagallo et al. 1994; Pettegrewet al. 1994; Parnetti et al. 1993; Sano et al. 1992; Canal et al. 1991; Spagnoli et al. 1991.

³For fish oil including species of Gadidae as a source material, the vitamin A and D content should be tested to ensure that the daily maximum amounts meet the Multi-Vitamin/Mineral Supplements monograph for each age group.

¹References consulted for the uses or purposes: EMA 2013; EMA 2010; ESCOP 2009; Bradley 2006; Christopher et al. 2005; Kennedy al. 2004; Taylor 2003; Barnes et al. 2002; Kamimori et al. 2000; Zwyghuizen- Doorenbos et al. 1990.

²References consulted for the doses: Health Canada 2018; EMA 2013; Health Canada 2012; EMA 2010; ESCOP 2009; Bradley 2006; Taylor 2003.

¹References consulted for the uses or purposes: Kanehira et al. 2011; Abdou et al. 2006.

²References consulted for the doses: Kanehira et al. 2011; Powers et al. 2007; Yamakoshi et al. 2006.

¹References consulted for the uses or purposes: Upton 2012; Winston and Maimes 2007; Mills and Bone 2005; API 2004; WHO 2004; Bone 2003; Hoffman 2003; Thomsen 2002; Williamson 2002; API 2001; Blumenthal et al. 2000; Upton 2000, 1999; WHO 1999; Bradley 1992.

²References consulted for the doses: Upton 2012; Winston and Maimes 2007; Mills and Bone 2005; API 2004, 2001; WHO 2004; Bone 2003; Hoffman 2003; Thomsen 2002; Williamson 2002; Kapoor 2001; Blumenthal et al. 2000; Upton 1999; WHO 1999; Bradley 1992.

¹References consulted for the doses: Clewell et al. 2016; Taylor et al. 2016; Neufingerl et al. 2013; Ma et al. 2007; Sun et al. 1999.

Direction(s) for use

See Table 5 below.

Combination rules and restrictions

All medicinal ingredients included in this monograph may be combined across all groups, with the following restrictions:

Use or Purpose Restrictions

• A use or purpose statement is only acceptable if at least one medicinal ingredient associated with that statement is present at a dose at or above the minimum daily dose listed in Tables 2.1 to 2,6.
• Medicinal ingredients which do not meet the minimum daily dose for a use or purpose statement will be considered as acceptable complementary medicinal ingredients in product formulations.
• For multi-ingredient products making at least one claim based on traditional use:
  • To prevent the product from being represented as a "traditional medicine," any indicated traditional use claim must refer to the specific medicinal ingredient(s) and recognized traditional system of medicine from which the claim originates when 1) both traditional and modern claims are present or 2) when claims originate from multiple systems of traditional medicine (e.g. German chamomile is traditionally used in Herbal Medicine to help relieve restlessness and/or nervousness. Ashwagandha is traditionally used in Ayurveda to balance aggravated Vata.).
  • When ALL of the medicinal ingredients (MIs) in the product are used within the SAME identified system of traditional medicine AND the product makes ONLY traditional claims, listing of MIs in the traditional claim(s) is not required.

Rules for sedative (soporific) ingredients (table 2.2)

If sedative ingredients (table 2.2) are combined, the sum of the percentages of the maximum daily reference dose must not exceed 120%, for all sedative ingredients in the product (including sedative ingredients supported by other NNHPD monographs such as melatonin). Note that no single ingredient can exceed 100% of its maximum daily reference dose. Please see Table 3 below for a calculation example.

The calculations are performed as follows:

• Percentage of the Maximum Daily Reference Dose = [(Maximum Daily Recommended Dose on PLA form) / (Maximum Daily Monograph Reference Dose)] x 100%

Safety assessment - Sum of Percentages:

• In the example above, the sum of Percentages of the Maximum Daily Reference Dose is 89.6%, which is less than 120%. Safety of the combination of ingredients is therefore supported by the monograph.

Rules for Caffeine

• If a product contains caffeine from any source, it cannot contain a sedative at a therapeutic dose (table 2.2) and nervine/sedative/relaxation claims (tables 2.1, 2.2 & 2.5) are not permitted.
• Products containing a total amount of caffeine per day that meets the minimum therapeutic dose (100 mg/day) must indicate a use or purpose associated with caffeine.
• Products containing caffeine either synthetic, isolated or from plant materials must not:
  • indicate any uses or purpose related to healthy blood pressure or cardiovascular health at any dose (except if supported by a monograph for a medicinal ingredient providing caffeine such as green coffee bean extract).
  • indicate any uses or purpose related to the maintenance/support of good/general health at a daily dose of 40 mg or more total caffeine from all sources.
• The maximum amount of total caffeine permitted from all ingredients in the product is 400 mg/day, and 200 mg per single dose.
• If the total amount of caffeine provided by the combination of ingredients in the product (e.g. Yerba mate and Guarana) is equal to or higher than 40 mg per day, risk statements from the NNHPD Caffeine Monograph are required. Please see Table 5 below.
• Additional synthetic caffeine added to Guarana and/or Yerba mate extracts must be represented as a separate medicinal ingredient.
• When caffeine (from any source) is combined with theacrine and/or theobromine, the sum of the percentages of the maximum daily/single reference dose must not exceed 120% for these ingredients. Note that no single ingredient can exceed 100% of its maximum daily/single reference dose. Please see table 4 below.

See table 3 above for an example of calculations. In this example, the sum of Percentages of the Maximum Monograph Reference Single Dose is 95.9%, which is less than 120%. Safety of the combination of ingredients is therefore supported by the monograph.

Rules for Huperzine A

When combining Huperzia serrata extract and Huperzine A (isolate or synthetic), the total quantity of Huperzine A provided by the product cannot exceed 200 micrograms per day.

Duration(s) of Use

See Table 5 below.

Risk Information

Consult Table 5 for appropriate statements related to each medicinal ingredient. The medicinal ingredients in Table 5 are associated with the required numbered statements below.

1. As per the respective NNHPD monograph.

Duration(s) of Use

2. Products providing Huperzia serrata, Huperzine A, 300 mg or more GABA per day, or over 150 mg Theobromine per day: Ask a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 4 weeks.
3. Products providing 101 to 300 mg/day Theacrine: Ask a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 8 weeks.

Caution(s) and warning(s)

4. Ask a health care practitioner/health care provider/health care professional/doctor/ physician if symptoms persist or worsen.
5. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are pregnant or breastfeeding.
6. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are pregnant.
7. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are breastfeeding.
8. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you have a urinary tract disorder and/or kidney disease.
9. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you have kidney disease and/or a seizure disorder.
10. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you have high blood pressure or glaucoma.
11. Products providing Huperzia serrata, huperzine A, or over 150 mg/day theobromine: Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you have a cardiovascular or blood pressure condition.
12. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are taking medications which affect acetylcholine levels (cholinergic or anticholinergic drugs).
13. Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are taking dopaminergic or cholinergic drugs.
14. Products making a sustained attention claim: Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you have an attention deficit disorder with or without hyperactivity (ADD or ADHD).
15. When using this product exercise caution if you drive or use machinery as you may experience drowsiness.
16. Products providing 300 mg or more GABA per day: When using this product avoid taking with alcohol.

Contraindication(s)

17. Do not use this product if you are pregnant or breastfeeding.
18. Do not use this product if you are pregnant.
19. Do not use if you have gastrointestinal irritation.

Known adverse reaction(s)

20. Stop use and ask a health care practitioner/health care provider/health care professional/doctor/physician if you experience dizziness, unusual muscle cramping, agitation, gastrointestinal symptoms such as nausea, vomiting, diarrhea or excessive salivation.
21. Stop use and ask a health care practitioner/health care provider/health care professional/doctor/physician if hypersensitivity/allergy occurs.
22. Stop use if you experience severe stomach and/or intestinal irritation.
23. When using this product you may experience gastrointestinal discomfort/disturbances.
24. When using this product you may experience headaches or gastrointestinal disturbances.
25. When using this product (a) diuretic effect may occur.

References: Nakazaki et al. 2021; Clewell et al. 2016; Taylor et al. 2016; Kuhman et al. 2015, McGlade et al. 2015, Morasch et al. 2015, Baggott et al. 2013, Cotroneo et al. 2013; EFSA 2013; EMA 2013; Gardner and McGuffin 2013, Neufingerl et al. 2013, Yang et al. 2013, McGlade et al. 2012, Fiebich et al. 2011; AMR 2010; Morgan and Stevens 2010; Okun et al. 2010, Van den Bogaard et al. 2010; ESCOP 2009; Wang et al. 2009; Calabrese et al. 2008; CPS 2008; Li et al. 2008, Cornelis and El-Sohemy 2007; Powers et al. 2007; Bain et al.2006; Bradley 2006; Bui et al. 2006; Mills et al. 2006; Shils et al. 2006; Turner et al. 2006; Bouchard et al. 2005; Chandrasekaran et al. 2005; Haller et al. 2005; Noordzij et al. 2005; Nathan et al. 2004; Bone 2003; Zangara 2003; Avisar et al. 2002; Barnes et al. 2002; Berardi et al. 2002; Thomsen 2002; Brinker 2001; Nathan et al. 2001; Stough et al. 2001; Arya et al. 2000; Pepping 2000; Vahedi et al. 2000; Jee et al. 1999; Sun et al. 1999; Mester et al. 1995; Xu et al. 1995, Bradley 1992; Zimmerman 1992; Creighton and Stanton 1990; Rai et al. 1990; Jefferson 1988.

Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database (NHPID) and must meet the limitations outlined in the database.

Storage conditions

Must be established in accordance with the requirements described in the Natural Health Products Regulations.

Products containing Cod liver oil, Fish oil or Schizochytrium oil

(except when encapsulated)

Refrigerate after opening (Senanayake and Fichtali 2006; Wille and Gonus 1989).

(information for industry; not for labelling)

To be packaged in airtight container, protected from light (Ph.Eur. 2023; USP-NF 2023).

Specifications

• The finished product specifications must be established in accordance with the requirements described in the Natural and Non-prescription Health Products Directorate (NNHPD) Quality of Natural Health Products Guide.
• The medicinal ingredient must comply with the requirements outlined in the NHPID.
• For the following ingredients please see the respective NNHPD monograph for additional quality requirements: Astragalus, American ginseng, Cod liver oil, Eleuthero, Fish oil, German chamomile-Oral, Gingko biloba, Hops, Licorice, Panax ginseng, St John's wort, L-Tyrosine, L-Theanine, Valerian.

EXAMPLE OF PRODUCT FACTS:

Consult the Guidance Document, Labelling of Natural Health Products for more details.

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