Cognitive Function Products

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.

Notes

Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's discretion.
The solidus (/) indicates that the terms and/or statements are synonymous. Either term or statement may be selected by the applicant.

Date

April 26, 2024

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

Table 1.1. Proper name(s), Common name(s), Source information for ingredients with nervine action
Proper name(s)	Common name(s)	Source information
Proper name(s)	Common name(s)	Source material(s)	Part(s)	Preparation(s)
Anemone pulsatilla	European pasqueflower Pasqueflower Pulsatilla	Anemone pulsatilla	Herb top	Dry¹
Avena sativa	Common oat Oat Red oat Side oat Tree oat	Avena sativa	Seed Herb top	Dry
Hypericum perforatum	Goatweed Hypericum St. John's wort St. John's-wort	Hypericum perforatum	Herb top	Dry
5-Hydroxy-L-tryptophan L-5-Hydroxytryptophan	L-5-HTP L-5-Hydroxytryptophan	Griffonia simplicifolia²	Seed	N/A
		Saccharomyces cerevisiae	Whole cell for biosynthesis	N/A
		Escherichia coli	Whole cell for biosynthesis	N/A
Nepeta cataria	Catmint Catnep Catnip Catswort Field balm	Nepeta cataria	Herb top	Dry
Matricaria chamomilla	Blue chamomile Chamomile Common chamomile German chamomile Hungarian chamomile Matricaria Scented chamomile Scented mayweed Sweet false chamomile True chamomile Wild chamomile	Matricaria chamomilla	Flower	Dry
Melissa officinalis	Balm Bee balm Lemon balm Melissa	Melissa officinalis	Herb top	Dry
Panax quinquefolius	American ginseng Occidental ginseng Sang Shang Xi yang shen	Panax quinquefolius	Root	Dry
Scutellaria lateriflora	Helmet flower Hoodwort Mad-dog scullcap Quarter bonnet Scullcap Skullcap Virginian skullcap	Scutellaria lateriflora	Herb top	Dry
Stachys officinalis	Bishop's-wort Purple betony Wood betony	Stachys officinalis	Herb top	Dry
Tilia cordata	Linden Littleleaf linden Small-leaf European linden Small-leaf lime Small-leaf lime tree Small-leaf linden Tilia	Tilia cordata	Flower	Dry
Tilia platyphyllos	Big-leaf linden Broadleaf lime Large-leaf lime Large-leaf linden Linden Tilia	Tilia platyphyllos	Flower	Dry
Tilia x europaea	European Lime tree European linden Lime Lime tree Linden Tilia	Tilia x europaea	Flower	Dry
Turnera diffusa	Damiana	Turnera diffusa	Leaf Leaf and stem	Dry
Withania somnifera	Asgandh Ashwagandha Asvagandha Winter-cherry Withania	Withania somnifera	Root	Dry

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.

Table 1.2. Proper name(s), Common name(s), Source information for ingredients with sedative action
Proper name(s)	Common name(s)	Source information
Proper name(s)	Common name(s)	Source material(s)	Part(s)	Preparation(s)
Eschscholzia californica	California poppy	Eschscholzia californica	Herb top	Dry
Humulus lupulus	Bine European hop Hop Hops	Humulus lupulus	Strobile	Dry
Passiflora incarnata	Apricot-vine Maypop Maypop passionflower Passionflower	Passiflora incarnata	Herb top	Dry
Valeriana officinalis	Common valerian Garden-heliotrope Garden valerian Valerian	Valeriana officinalis	Root Root and rhizome	Dry

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

Table 1.3. Proper name(s), Common name(s), Source information for ingredients with cognitive support action
Proper name(s)	Common name(s)	Source information
Proper name(s)	Common name(s)	Source ingredient(s)	Source material(s)	Organism group(s)	Part(s)	Preparation(s)
(2R)-2-(Acetyloxy)-3-carboxy-N,N,N-trimethyl-1-propanaminium inner salt	Acetylcarnitine	Acetyl-L-carnitine arginate dihydrochloride² Acetyl L-carnitine hydrochloride¹	N/A	N/A	N/A	N/A
Bacopa monnieri	Bacopa Moneywort Water hyssop	N/A	Bacopa monnieri	N/A	Herb top Whole plant	Dry
2-[[[(2R)-2,3-Dihydroxypropoxy]hydroxyphosphinyl]oxy]-N,N,N-trimethylethanaminium hydroxide • inner salt d-Choline hydroxide 2,3-dihydroxypropylhydrogen phosphate inner salt L-alpha-Glycerylphosphorylcholine	Choline alfoscerate	Choline alfoscerate¹	N/A	N/A	N/A	N/A
Choline cytidine 5'-pyrophosphate (ester) Cytidine 5'-(trihydrogen diphosphate) P'-[2(trimethylammonio)ethyl] ester inner salt Cytidine 5'-diphosphocholine	Citicoline	Citicoline sodium¹ Citicoline¹	N/A	N/A	N/A	N/A
Cod liver oil	Cod liver oil Lecoris Aselli Oleum	N/A	N/A	Gadidae³	Liver	N/A
Eleutherococcus senticosus	Ci wu jia Eleuthero Siberian ginseng	N/A	Eleutherococcus senticosus	N/A	Root	Dry
Fish oil	Fish oil	N/A	N/A	Ammodytidae Carangidae Clupeidae Engraulidae Gadidae³ Osmeridae Salmonidae Scombridae	Whole	N/A
Ginkgo biloba	Ginkgo Ginkgo biloba Maidenhair tree Baiguo Icho	N/A	Ginkgo biloba	N/A	Leaf	N/A
Panax ginseng	Asian ginseng Chinese ginseng Hong shen Korean ginseng Korean red ginseng Oriental ginseng Panax ginseng Red ginseng Ren shen	N/A	Panax ginseng	N/A	Root Rootlet	Dry
Phosphatidylserine	Phosphatidylserine	N/A	Helianthus annuus ²	N/A	Seed	N/A
		Phosphatidylserine-enriched soy lecithin¹	N/A	N/A	N/A	N/A
		Phosphatidylserine¹	N/A	N/A	N/A	N/A
Rhodiola rosea	Hong jing tian King's-crown Rhodiola Roseroot	N/A	Rhodiola rosea	N/A	Root Root and rhizome	Dry
Schizochytrium spp.	Schizochytrium Oil	N/A	Schizochytrium spp.	N/A	Whole	N/A
(S)-alpha-Amino-4- hydroxybenzenepropanoic acid L-Tyrosine	L-Tyrosine Tyrosine	L-Tyrosine ethyl ester¹ N-Acetyl-L-tyrosine¹	N/A	N/A	N/A	N/A
Withania somnifera	Asgandh Ashwagandha Asvagandha Winter-cherry Withania	N/A	Withania somnifera	N/A	Root	Dry

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.

Table 1.4. Proper name(s), Common name(s), Source information for caffeine and ingredients containing caffeine
Proper name(s)	Common name(s)	Source information
Proper name(s)	Common name(s)	Source ingredient(s)	Source material(s)	Part(s)	Preparation(s)
1,3,7-Trimethylxanthine 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione	Caffeine	Caffeine¹ Caffeine citrate¹	N/A	N/A	N/A
		N/A	Camellia sinensis²	Leaf	N/A
		N/A	Coffea arabica² Coffea canephora²	Seed	N/A
		N/A	Cola acuminata²	Seed	N/A
		N/A	Ilex paraguariensis² Ilex guayusa²	Leaf	N/A
		N/A	Paullinia cupana²	Seed	N/A
		N/A	Theobroma cacao²	Seed	N/A
Ilex paraguariensis	Brazilian tea Mate Paraguayan tea Paraguay tea St Bartholomew's tea Yerba mate	N/A	Ilex paraguariensis	Leaf	Dry
Paullinia cupana	Guarana	N/A	Paullinia cupana	Seed	Dry

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.

Table 1.5. Proper name(s), Common name(s), Source information for ingredients with action
Proper name(s)	Common name(s)	Source information
Proper name(s)	Common name(s)	Source ingredient(s)	Source material(s)	Part(s)
4-Aminobutanoic acid	GABA gamma-Aminobutyric acid	N/A	Lentilactobacillus hilgardii²	Whole cell for biosynthesis
		N/A	Levilactobacillus brevis²	Whole cell for biosynthesis
		N/A	Laminaria japonica²	Whole
		4-Aminobutanoic acid¹	N/A	N/A
L-Theanine N-Ethyl-L-glutamine	L-Theanine	N/A	Camellia sinensis²	Leaf
L-Theanine N-Ethyl-L-glutamine	L-Theanine	L-Theanine¹	N/A	N/A

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

Table 1.6. Proper name(s), Common name(s), Source information for ingredients with adaptogen action
Proper name(s)	Common name(s)	Source information
Proper name(s)	Common name(s)	Source material(s)	Part(s)	Preparation
Asparagus racemosus	Shatamuli Shatavari	Asparagus racemosus	Root	Dry
Astragalus membranaceus	Astragalus Huangqi Huang qi Membranaceus milk vetch Membranous milk-vetch Milk vetch root Mo jia huang qi	Astragalus membranaceus	Root	Dry
Eleutherococcus senticosus	Ci wu jia Eleuthero Siberian ginseng	Eleutherococcus senticosus	Root Root and rhizome	Dry
Ganoderma lucidum	Ganoderma Ling zhi Reishi	Ganoderma lucidum	Cultured mycelium fruiting body Mycelium	Dry
Glycyrrhiza glabra	Guang guo gan cao Licorice Liquorice	Glycyrrhiza glabra	Root Root and stolon	Dry
Ocimum tenuiflorum	Holy basil Rama tulsi Sacred basil Tulsi	Ocimum tenuiflorum	Leaf	Dry
Panax ginseng	Asian ginseng Chinese ginseng Hong shen Korean ginseng Korean red ginseng Oriental ginseng Panax ginseng Red ginseng Ren shen	Panax ginseng	Root Rootlet	Dry
Panax quinquefolius	American ginseng Occidental ginseng Sang Shang Xi yang shen	Panax quinquefolius	Root	Dry
Rhodiola rosea	Hong jing tian King's-crown Rhodiola Roseroot	Rhodiola rosea	Root Root and rhizome	Dry
Schisandra chinensis	Chinese Magnoliavine Schisandra Wu wei zi	Schisandra chinensis	Fruit	Dry
Tinospora cordifolia	Guduchi	Tinospora cordifolia	Stem	Dry
Withania somnifera	Asgandh Ashwagandha Asvagandha Winter-cherry Withania	Withania somnifera	Root Whole plant	Dry

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.

Table 1.7. Proper name(s), Common name(s), Source information for complementary ingredients
Proper name(s)	Common name(s)	Source information
Proper name(s)	Common name(s)	Source ingredient(s)	Source material(s)	Part(s)	Preperation(s)
[5R-(5alpha,9beta, 11E)]-5-Amino-11-ethylidne-5,6,9, 1-tetrahydro-7-methyl-5,9-methano cycloocta [b]pyridine-2(1H)-one	Huperzine A	Huperzine A¹	Huperzia serrata²	Whole plant	Dry
7,9-Dihydro-1,3,7,9-tetramethyl-1H-purine-2,6,8(3H)-trione	Theacrine	Theacrine¹	Camellia sinensis²	Leaf	Dry
7,9-Dihydro-1,3,7,9-tetramethyl-1H-purine-2,6,8(3H)-trione	Theacrine	Theacrine¹	Theobroma grandiflorum²	Fruit	Dry
3,7-Dihydro-3,7-dimethyl-1H-purine-2,6-dione 3,7-Dimethylxanthine	Theobromine	N/A	Theobroma cacao	Seed	Dry
Huperzia serrata	Toothed club-moss Toge-shiba	N/A	Huperzia serrata	Whole plant	Dry

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.

Table 2.1. Cognitive function uses or purposes and associated daily doses for ingredients with nervine action
Uses or Purposes¹	Medicinal Ingredients	Methods of preparation	Doses/day²
(Traditionally) used in Herbal Medicine to help relieve restlessness and/or nervousness (nervine/calmative)	Anemone pulsatilla (Pasqueflower)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	0.03-0.6 grams dried herb top, per day
	Anemone pulsatilla (Pasqueflower)	Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	0.1-0.9 grams dried herb top, per day
	Avena sativa (Oat)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	0.6-20 grams dried seed, per day 3 grams dried herb top, per day
	Nepeta cataria (Catnip)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	1.2-12 grams dried herb top, per day
	Panax quinquefolius (American ginseng)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	0.5-12 grams dried root, per day
	Tilia cordata (Small-leaf linden)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	1.5-12 grams dried flower, per day
	Tilia platyphyllos (Large-leaf linden)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	1.5-12 grams dried flower, per day
	Tilia x europaea (European Linden)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	1.5-12 grams dried flower, per day
	Turnera diffusa (Damiana)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	1.5-4 grams dried leaf/leaf and stem, per day
(Traditionally) used in Herbal Medicine to help relieve restlessness and/or nervousness (nervine/calmative)	Hypericum perforatum (St. John's wort)	Dry, Powder, Non- Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	2-12.6 grams dried herb top, per day; Not to exceed 4.2 grams per single dose
Used in Herbal Medicine to help relieve restlessness and/or nervousness (nervine/calmative) AND/OR (Used in Herbal Medicine to) help(s) relieve sleep disturbances associated with mood imbalance	Hypericum perforatum (St. John's wort)	Standardized Extracts (Dry extract)	600-1800 milligrams of dried herb top extract, per day, standardized to 3-6% hyperforin and/or 0.12- 0.28% hypericin; Not to exceed 600 milligrams of extract per single dose
Helps (to) relieve sleep disturbances associated with mood imbalance	L-5-Hydroxytryptophan (L-5-HTP)	Isolate	100-200 milligrams, per day
(Traditionally) used in Herbal Medicine to help relieve restlessness and/or nervousness (which helps to promote sleep) (nervine/calmative)	Matricaria chamomilla (German chamomile)	Dry, Powder, Non- Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	1.5-24 grams dried flower, per day
	Melissa officinalis (Lemon balm)	Dry, Powder, Non- Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	0.4-13.5 grams dried herb top, per day
	Scutellaria lateriflora (Skullcap)	Dry, Powder, Non- Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	0.25-12 grams dried herb top, per day
	Scutellaria lateriflora (Skullcap)	Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	3-12 grams dried herb top, per day
	Stachys officinalis (Wood betony)	Dry, Powder, Non- Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	2-4 grams dried herb top, per day
Traditionally used in Ayurveda to balance aggravated Vata (nervine) AND/OR Traditionally used in Ayurveda to help relieve restlessness and/or nervousness (which helps to promote sleep).	Withania somnifera (Ashwagandha)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	2-6 grams dried root, per day

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.

Table 2.2. Cognitive function uses or purposes and associated daily doses for ingredients with sedative (soporific) action
Uses or Purposes¹	Medicinal Ingredients	Methods of preparation	Doses/day²
(Traditionally) used in Herbal Medicine as a sleep aid (during times of mental stress). AND/OR (Traditionally) used in Herbal Medicine to help relieve restlessness and/or nervousness (calmative).	Eschscholzia californica (California poppy)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	0.2-3 grams dried herb top, per day
	Humulus lupulus (Hops)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	0.5-6 grams dried strobile, per day
	Passiflora incarnata (Passionflower)	Dry, Powder, Non- Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	0.25-8 grams dried herb top, per day
	Passiflora incarnata (Passionflower)	Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	1-8 grams dried herb top, per day
(Traditionally used in Herbal Medicine as a) sleep aid/(to) help(s) to promote sleep. AND/OR (Traditionally) used in Herbal Medicine to relieve restlessness and/or nervousness (calmative)	Valeriana officinalis (Valerian)	Dry, Powder, Non- Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	0.3-12 grams dried root/root and rhizome, per day; Not to exceed 3.6 grams per single dose
	Valeriana officinalis (Valerian)	Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	0.3-12 grams of dried root/root and rhizome, per day³; Not to exceed 3.6 grams per single dose and: 0.05-0.90% valerenic acid OR 0.10-0.90% sesquiterpenic acids

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.

Table 2.3. Cognitive function uses or purposes and associated daily doses for ingredients with with cognitive support action
Uses or Purposes¹	Medicinal Ingredients	Methods of preparation	Doses/day²
Helps support cognitive/brain health/function.	Acetylcarnitine	N/A	1.5-4 grams, per day
	Bacopa monnieri (Bacopa)	Standardized Extracts (Dry extract)	300 milligrams dried whole plant/herb top extract, per day, standardized to 40-55% bacosides
	Cod liver oil	Standardized fixed oil	18 years: 0.77-4 grams Cod liver oil, per day And 150-1,360 milligrams EPA + DHA including at least 100 milligrams DHA, per day And 138-2,800 micrograms RAE (vitamin A), per day And 1.15-23.12 micrograms vitamin D3, per day
	Cod liver oil	Standardized fixed oil	19 years and older: 0.77-4 grams Cod liver oil, per day And 150-1,360 milligrams EPA + DHA including at least 100 milligrams DHA, per day And 138-3,000 micrograms RAE (Vitamin A), per day And 1.15-25 micrograms Vitamin D3, per day
	L-alpha-Glycerophosphorylcholine (Choline alfoscerate)	N/A	1.2 grams, per day
	Fish oil	Standardized fixed oil	150-5,000 milligrams EPA and DHA including at least 100 milligrams DHA, per day³
	Phosphatidylserine	N/A	300 milligrams, per day
	Schizochytrium oil	Standardized fixed oil	200-2,000 milligrams DHA, per day
Helps (to) support memory	Bacopa monnieri (Bacopa)	Standardized Extracts (Dry extract)	300 milligrams dried whole plant/herb top extract, per day, standardized to 40- 55% bacosides
Traditionally used in Ayurveda for memory enhancement	Bacopa monnieri (Bacopa)	Dry, Powder, Non- Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	1-6.5 grams dried whole plant/herb top, per day
Traditionally used in Ayurveda for memory enhancement	Withania somnifera (Ashwagandha)	Dry, Powder, Non- Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	2-6 grams dried root, per day
Helps (to) improve sustained attention.	Citicoline	N/A	250-1000 milligrams per day; not to exceed 500 milligrams per single dose
Helps (to) support cognitive health and/or brain function in older adults.	Citicoline	N/A	500-1000 milligrams per day; not to exceed 500 milligrams per single dose
Used in Herbal Medicine to help improve mental performance after periods of mental exertion	Eleutherococcus senticosus (Eleuthero)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	0.91-6 grams dried root, per day
Helps (to) enhance cognitive function and/or memory in adults	Ginkgo biloba (Ginkgo)	Standardized Extracts (Dry extract)	80-240 milligrams of extract, per day (50:1; quantity crude equivalent 4 - 12 g of dried leaves, per day) providing at least 80 milligrams of extract per single dose and standardized to: 22-27% flavonoid glycosides And 5-7% terpene lactones
(Used in Herbal Medicine to) help(s) support cognitive function and/or reduce mental fatigue (in cases of mental stress) AND/OR Helps support cognition	Panax ginseng (Panax ginseng)	Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid Extract, Decoction, Infusion)	0.5-9 grams dried root/ rootlet, per day
	Panax ginseng (Panax ginseng)	Standardized Extracts (Dry extract)	200-600 milligrams of extract, per day; standardized to 4-7% total ginsenosides; Not to exceed a quantity crude equivalent of 9 grams of dried root/rootlet, per day
(Used in Herbal Medicine) (to) help(s) support cognitive function (such as mental focus and mental stamina)	Rhodiola rosea (Rhodiola)	Tincture	1.2-1.8 grams of dried root/root and rhizome, per day
	Rhodiola rosea (Rhodiola)	Standardized Extracts (Dry extract)	144-680 milligrams of dried root/root and rhizome extract, per day; Not to exceed 200 milligrams per single dose and: 0.8-3% salidroside And/Or 1-6% rosavins
Helps to decrease cognitive fatigue due to physically stressful situations (e.g. extended wakefulness, exposure to cold, excessive noise).	L-Tyrosine	N/A	10-20 grams, per day; Not to exceed 10 grams per single dose

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.

Table 2.4. Cognitive function uses or purposes and associated daily doses for caffeine and ingredients containing caffeine
Uses or Purposes¹	Medicinal Ingredients	Methods of preparation	Doses/day²
Helps (temporarily) (to) promote alertness and wakefulness, and (to) enhance cognitive performance AND/OR Helps (temporarily) (to) relieve/reduce fatigue/tiredness AND/OR Helps (temporarily) (to) support/promote mental sharpness/alertness	1,3,7-Trimethylxanthine (Caffeine)	N/A	100-400 milligrams, per day and 100-200 milligrams per single dose
	Ilex paraguariensis (Yerba mate)	Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	Extract standardized to caffeine corresponding to a maximum Quantity Crude Equivalent of 6 grams dried leaf, per day; not exceeding 150 milligrams caffeine per day; and providing 100-150 milligrams caffeine per single dose
	Paullinia cupana (Guarana)	Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	Extract standardized to caffeine corresponding to a maximum Quantity Crude Equivalent of 3 grams dried seed per day and not exceeding 200 milligrams caffeine per day; and providing 100-200 milligrams caffeine per single dose
Used in Herbal Medicine to help temporarily promote alertness and wakefulness, and to enhance cognitive performance	Ilex paraguariensis (Yerba mate)	Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	Extract standardized to caffeine corresponding to a Quantity Crude Equivalent of 3-6 grams dried leaf, per day and not exceeding 150 milligrams caffeine per day
	Ilex paraguariensis (Yerba mate)	Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	Extract standardized to caffeine corresponding to a Quantity Crude Equivalent of 2-6 grams dried leaf, per day and not exceeding 150 milligrams caffeine per day
	Paullinia cupana (Guarana)	Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	Extract standardized to caffeine corresponding to a Quantity Crude Equivalent of 1-3 grams dried seed, per day and not exceeding 200 milligrams caffeine per day

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.

Table 2.5. Cognitive function uses or purposes and associated daily doses for ingredients with relaxation action
Uses or Purposes¹	Medicinal Ingredients	Methods of preparation	Doses/day²
Helps (to) temporarily promote relaxation	4-Aminobutanoic acid (GABA)	N/A	50-3,000 milligrams, per day; Not to exceed 750 milligrams per single dose
Helps (to) temporarily promote relaxation	L-Theanine	N/A	200-250 milligrams, per day

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.

Table 2.6. Cognitive function uses or purposes and associated daily doses for ingredients with adaptogen action
Uses or Purposes¹	Medicinal Ingredients	Methods of preparation	Doses/day²
Used in Herbal Medicine as an adaptogen to help increase energy and resistance to stress over time (e.g. in case of mental and physical fatigue related to stress)	Asparagus racemosus (Shatavari)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	2-6 grams dried root, per day
	Astragalus membranaceus (Astragalus)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	2-4.8 grams dried root, per day
	Eleutherococcus senticosus (Eleuthero)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	1-6 grams dried root/root and rhizome, per day
	Eleutherococcus senticosus (Eleuthero)	Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	2-3 grams dried root/root and rhizome, per day
	Ganoderma lucidum (Reishi)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	1.5-6 grams dried cultured mycelium/ fruiting body/mycelium, per day
		Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	1.5-6 grams of dried cultured mycelium/ fruiting body/mycelium, per day and not to exceed 40 % polysaccharides
		Decoction, Decoction concentrate	3-15 grams dried cultured mycelium/ fruiting body/mycelium, per day
		Decoction Standardized, Decoction concentrate Standardized	3-15 grams dried cultured mycelium/ fruiting body/mycelium, per day and not to exceed 40 % polysaccharides
	Glycyrrhiza glabra (Licorice)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	0.6-6 grams dried root/root and stolon, per day
	Ocimum tenuiflorum (Holy basil)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	2-3 grams dried leaf, per day
	Ocimum tenuiflorum (Holy basil)	Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	4.2-28 grams dried leaf, per day
	Panax ginseng (Panax ginseng)	Dry, Powder, Non- Standardized Extracts (Dry extract, Tincture, Fluid Extract, Decoction, Infusion)	0.5-9 grams dried root/ rootlet, per day
	Panax ginseng (Panax ginseng)	Standardized Extracts (Dry extract)	200-600 milligrams of extract, per day; standardized to 4-7% total ginsenosides; Not to exceed a quantity crude equivalent of 9 grams dried root/rootlet, per day
	Panax quinquefolius (American ginseng)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	1-3 grams dried root, per day
	Panax quinquefolius (American ginseng)	Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	6-9 grams dried root, per day; Not to exceed 3 grams per single dose
	Rhodiola rosea (Rhodiola)	Non-Standardized Ethanolic Extracts (Dry extract)	144-400 milligrams of dry extract and a quantity crude equivalent of 216-2,000 milligrams of dried root/root and rhizome, per day; Not to exceed 200 milligrams of dry extract and a QCE of 1 gram of dried root/root and rhizome, per single dose
		Tincture	1.2-1.8 grams of dried root/root and rhizome, per day
		Standardized Extracts (Dry extract)	144-680 milligrams of dried root/root and rhizome extract, per day; Not to exceed 200 milligrams per single dose and: 0.8 - 3% salidroside And/Or 1 - 6% rosavins
	Schisandra chinensis (Schisandra)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract	1.2-6 grams dried fruit, per day
	Schisandra chinensis (Schisandra)	Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)	1.5-6 grams dried fruit, per day
	Tinospora cordifolia (Guduchi)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	0.9-3 grams dried stem, per day
	Tinospora cordifolia (Guduchi)	Decoction, Decoction concentrate	20-30 grams dried stem, per day
	Withania somnifera (Ashwagandha)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract	2.5-6.5 grams dried root/whole plant, per day
(Used as an adaptogen) (to) help(s) (to) temporarily relieve symptoms of stress (such as mental fatigue and sensation of weakness)	Rhodiola rosea (Rhodiola)	Non-Standardized Ethanolic Extracts (Dry extract)	144-400 milligrams dry extract and a Quantity Crude Equivalent (QCE) of 216-2,000 milligrams of dried root/root and rhizome, per day; Not to exceed 200 milligrams of extract and a QCE of 1 gram of dried root/root and rhizome, per single dose
		Tincture	1.2-1.8 grams of dried root/root and rhizome, per day
		Standardized Extracts (Dry extract)	144-680 milligrams of dried root/root and rhizome extract, per day; Not to exceed 200 milligrams per single dose and: 0.8 - 3% salidroside And/Or 1 - 6% rosavins
Traditionally used in Ayurveda as Rasayana (rejuvenative tonic)	Asparagus racemosus (Shatavari)	Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)	3-6 grams dried root, per day
	Withania somnifera (Ashwagandha)	Dry, Powder, Non- Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)	2-6 grams dried root, per day

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.

Table 2.7. Maximum daily doses for complementary ingredients with no associated recommended use
Medicinal Ingredients	Methods of preparations	Doses/day¹
Huperzia serrata (Toothed club-moss)	Standardized extracts (Dry extract)	Up to 20 milligrams extract standardized to huperzine A, per day; Not to exceed 1% huperzine A potency
Huperzine A	N/A	Up to 200 micrograms, per day
Theacrine	N/A	Up to 300 milligrams, per day
Theobromine	N/A	Up to 850 milligrams, per day

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.

Table 3. Combination Table to assess Safety of Sedative/Soporific Ingredients
Additive Indication	e.g. Used in Herbal Medicine as a sleep aid
Medicinal Ingredients	Maximum Daily Recommended Dose on PLA form	Maximum Daily Monograph Reference Dose	Percentage of the Maximum Daily Reference Dose (%)
Eschscholzia californica (California poppy)	0.5 g	3 g	0.5/3 = 16.67%
Humulus lupulus (Hops)	4 g	6 g	4/6 = 66.66%
Passiflora incarnata (Passionflower)	0.5 g	8 g	0.5/8 = 6.25%
Sum of Percentages			89.6%

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.

Table 4. Combination Table to assess safety of ingredients with a caution for cardiovascular and/or blood pressure conditions.
Additive Effect	Ingredients which may have an impact on heart rate and/or blood pressure
Medicinal Ingredients	Maximum Daily/ Single Recommended Dose on PLA form	Maximum Daily/ Single Monograph Reference Dose	Percentage of the Maximum Daily/ Single Reference Dose (%)
Caffeine	100 mg	200 mg per single dose/400 mg per day	100/200 = 50% (single dose) 100/400 = 25% (day)
Theacrine	120 mg	300 mg	120/300 = 40%
Theobromine	50 mg	850 mg	50/850 = 5.9%
Sum of Percentages			95.9% per single dose/ 70.9% per day

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.

As per the respective NNHPD monograph.

Duration(s) of Use

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.
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)

Ask a health care practitioner/health care provider/health care professional/doctor/ physician if symptoms persist or worsen.
Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are pregnant or breastfeeding.
Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are pregnant.
Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are breastfeeding.
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.
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.
Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you have high blood pressure or glaucoma.
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.
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).
Ask a health care practitioner/health care provider/health care professional/doctor/ physician before use if you are taking dopaminergic or cholinergic drugs.
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).
When using this product exercise caution if you drive or use machinery as you may experience drowsiness.
Products providing 300 mg or more GABA per day: When using this product avoid taking with alcohol.

Contraindication(s)

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

Known adverse reaction(s)

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.
Stop use and ask a health care practitioner/health care provider/health care professional/doctor/physician if hypersensitivity/allergy occurs.
Stop use if you experience severe stomach and/or intestinal irritation.
When using this product you may experience gastrointestinal discomfort/disturbances.
When using this product you may experience headaches or gastrointestinal disturbances.
When using this product (a) diuretic effect may occur.

Table 5. Risk information, durations of use, and directions for use associated with medicinal ingredients
Medicinal Ingredients	Risk Information	Durations of Use	Directions for use
1,3,7-Trimethylxanthine (Caffeine)	1		1
4-Aminobutanoic acid (GABA)	5,16	2
Acetyl-L-Carnitine (Acetylcarnitine)	5, 9, 23
Anemone pulsatilla (Pasqueflower)	4, 8, 17, 19, 22
Asparagus racemosus (Shatavari)	6
Astragalus membranaceus (Astragalus)	1
Avena sativa (Oat)	4
Bacopa monnieri (Bacopa)	5, 23
Citicoline	5, 13, 14, 24
Cod liver oil	1
Eleutherococcus senticosus (Eleuthero)	1	1
Eschscholzia californica (California poppy)	1		1
Fish oil	1
Ganoderma lucidum (Reishi)	1		1
Ginkgo biloba (Ginkgo)	1	1
Glycyrrhiza glabra (Licorice)	1	1
Humulus lupulus (Hops)	1		1
Huperzia serrata; Huperzine A	11, 12, 17, 20	2
Hypericum perforatum (St. John's wort)	1	1
Ilex paraguariensis (Yerba mate)	5, 10, 21, 25
L-5-Hydroxytryptophan (L-5-HTP)	1	1	1
L-alpha-Glycerophosphorylcholine (Choline alfoscerate)	5
L-Theanine	1
L-Tyrosine	1	1	1
Matricaria chamomilla (German chamomile)	1
Melissa officinalis (Lemon balm)	1
Nepeta cataria (Catnip)	1
Ocimum tenuiflorum (Holy basil)	1
Panax ginseng (Asian ginseng)	1	1
Panax quinquefolius (American ginseng)	1
Passiflora incarnata (Passionflower)	1		1
Paullinia cupana (Guarana)	5, 10, 21, 25
Phosphatidylserine	1
Rhodiola rosea (Rhodiola)	1
Schisandra chinensis (Schisandra)	7, 18
Scutellaria lateriflora (Skullcap)	1
Stachys officinalis (Wood Betony)	4, 5, 15
Theacrine	5, 10	3
Theobromine	5, 11, 23	2
Tilia cordata (Small-leaf linden)	1
Tilia platyphyllos (Large-leaf linden)	1
Tilia x europaea (European linden)	1
Tinospora cordifolia (Guduchi)	5
Turnera diffusa (Damiana)	4, 7, 18
Valeriana officinalis (Valerian)	1		1
Withania somnifera (Ashwagandha)	1
Combination of ingredients resulting in a total caffeine content of 40 mg/day or more (e.g. Yerba mate and Guarana extracts)	as per the caffeine monograph		as per the caffeine monograph

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.

Product Facts Table

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