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Drugs and Health Products

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

March 25, 2019

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

Table 1. Proper name(s), Common name(s), Source material(s)
Proper name(s) Common name(s) Source material(s)
Proper name(s) Part(s) Preparation

Group 1: Ingredients with nervine action

Anemone pulsatilla

  • European pasqueflower
  • Pasqueflower
  • Pulsatilla

Anemone pulsatilla

Herb top

Dried1

Avena sativa

  • Common oat
  • Oat
  • Red oat
  • Side oat
  • Tree oat

Avena sativa

Seed

Dried

Nepeta cataria

  • Catmint
  • Catnep
  • Catnip
  • Catswort
  • Field balm

Nepeta cataria

Herb top

Dried

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

Dried

Panax quinquefolius

  • American ginseng
  • Occidental ginseng
  • Sang
  • Shang
  • Xi yang shen

Panax quinquefolius

Root

Dried

Tilia cordata

  • Linden
  • Littleleaf linden
  • Small-leaf European linden
  • Small-leaf lime
  • Small-leaf lime tree
  • Small-leaf linden
  • Tilia

Tilia cordata

Flower

Dried

Tilia platyphyllos

  • Big-leaf linden
  • Broadleaf lime
  • Large-leaf lime
  • Large-leaf linden
  • Linden
  • Tilia

Tilia platyphyllos

Flower

Dried

Tilia x europaea

  • European Lime tree
  • European linden
  • Lime
  • Lime tree
  • Linden
  • Tilia

Tilia x europaea

Flower

Dried

Turnera diffusa

Damiana

Turnera diffusa

  • Leaf
  • Leaf and stem

Dried

Withania somnifera

  • Asgandh
  • Ashwagandha
  • Asvagandha
  • Winter-cherry
  • Withania

Withania somnifera

Root

Dried

Group 2: Ingredients with sedative action

Proper name(s) Common name(s) Source material(s)
Proper name(s) Part(s) Preparation

Eschscholzia californica

California poppy

Eschscholzia californica

Herb top

Dried

Humulus lupulus

  • Bine
  • European hop
  • Hop
  • Hops

Humulus lupulus

Strobile

Dried

Hypericum perforatum

  • Goatweed
  • Hypericum
  • St. John's wort
  • St. John's-wort

Hypericum perforatum

Herb top

Dried

  • 5-Hydroxy-L-tryptophan
  • L-5-Hydroxytryptophan

  • L-5-HTP
  • L-5-Hydroxytryptophan

Griffonia simplicifolia

Seed

Dried

Melissa officinalis

  • Balm
  • Bee balm
  • Lemon balm
  • Melissa

Melissa officinalis

Herb top

Dried

Passiflora incarnata

  • Apricot-vine
  • Maypop
  • Maypop passionflower
  • Passionflower

Passiflora incarnata

Herb top

Dried

Scutellaria lateriflora

  • Helmet flower
  • Hoodwort
  • Mad-dog skullcap
  • Quarter bonnet
  • Scullcap
  • Skullcap
  • Virginian skullcap

Scutellaria lateriflora

Herb top

Dried

Stachys officinalis

  • Bishop's-wort
  • Purple betony
  • Wood betony

Stachys officinalis

Herb top

Dried

Valeriana officinalis

  • Common valerian
  • Garden-heliotrope
  • Garden valerian
  • Valerian

Valeriana officinalis

  • Root
  • Root and rhizome

Dried

Withania somnifera

  • Asgandh
  • Ashwagandha
  • Asvagandha
  • Winter-cherry
  • Withania

Withania somnifera

Root

Dried

Group 3: Ingredients with cognitive support action

Proper name(s) Common name(s) Source material(s)
Proper name(s) Common name(s) Organism group(s) Part(s) Preparation

(2R)-2-(Acetyloxy)-3-carboxy-N,N,N-trimethyl-1-propanaminium inner salt

Acetylcarnitine

N/A

  • Acetyl-L-carnitine arginate dihydrochloride
  • N-Acetyl L-carnitine hydrochloride

N/A

N/A

N/A

Bacopa monnieri

  • Bacopa
  • Moneywort
  • Water hyssop

Bacopa monnieri

N/A

N/A

Herb top

Dried

  • 2-[[[(2R)-2,3-Dihydroxypropoxy]
    hydroxyphosphinyl]oxy]-
    N,N,N-trimethylethanaminium hydroxide inner salt
  • d-Choline hydroxide 2,3- dihydroxypropyl hydrogen phosphate inner salt
  • L-alpha-Glycerylphosphorylcholine

Choline alfoscerate

N/A

Choline alfoscerate

N/A

N/A

Synthetic

Cod liver oil

  • Cod liver oil
  • Lecoris Aselli Oleum

N/A

N/A

Gadidae

Liver

N/A

Eleutherococcus senticosus

  • Ci wu jia
  • Eleuthero
  • Siberian ginseng

Eleutherococcus senticosus

N/A

N/A

Root

Dried

Fish oil

Fish oil

N/A

N/A

  • Ammodytidae
  • Carangidae
  • Clupeidae
  • Engraulidae
  • Osmeridae
  • Salmonidae Scombridae

Whole

N/A

Ginkgo biloba

  • Ginkgo
  • Ginkgo biloba
  • Maidenhair tree
  • Baiguo
  • Icho

Ginkgo biloba

N/A

N/A

Leaf

N/A

Panax ginseng

  • Asian ginseng
  • Chinese ginseng
  • Hong shen
  • Korean ginseng
  • Korean red ginseng
  • Oriental ginseng
  • Panax ginseng
  • Red ginseng
  • Renshen

Panax ginseng

N/A

N/A

  • Root
  • Rootlet

Dried

Phosphatidylserine

Phosphatidylserine

Helianthus annuus

N/A

N/A

Seed

N/A

N/A

Phosphatidylserine-enriched soy lecithin

N/A

N/A

N/A

N/A

Phosphatidylserine

N/A

N/A

Synthetic

Rhodiola rosea

  • Hong jing tian
  • King's-crown
  • Rhodiola
  • Roseroot

Rhodiola rosea

N/A

N/A

  • Root
  • Root and rhizome

Dried

Schizochytrium spp.

Schizochytrium Oil

Schizochytrium spp.

N/A

N/A

Whole

N/A

Group 4: Caffeine/Ingredients containing caffeine

Proper name(s) Common name(s) Source material(s)
Proper name(s) Common name(s) Part(s) Preparation

  • 1,3,7-trimethylxanthine
  • 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Caffeine

N/A

  • Caffeine
  • Caffeine citrate

N/A

Synthetic

Ilex paraguariensis

  • Brazilian tea
  • Mate

Ilex paraguariensis

N/A

Leaf

Dried

Paullinia cupana

Guarana

Paullinia cupana

N/A

Seed

Dried

Group 5: Ingredient with action on cognitive fatigue

Proper name(s) Common name(s) Source material(s)
Common name(s) Preparation

  • (S)-alpha-Amino-4-hydroxybenzenepropanoic acid
  • L-Tyrosine

  • L-Tyrosine
  • Tyrosine

  • L-Tyrosine ethyl ester
  • N-Acetyl tyrosine

N/A

Group 6: Ingredients with action on memory

Proper name(s) Common name(s) Source material(s)
Proper name(s) Part(s) Preparation

Bacopa monnieri

  • Bacopa
  • Moneywort
  • Water hyssop

Bacopa monnieri

  • Whole plant
  • Herb top

Dried

Withania somnifera

  • Asgandh
  • Ashwagandha
  • Asvagandha
  • Winter-cherry
  • Withania

Withania somnifera

Root

Dried

Group 7: Ingredients with relaxation action

Proper name(s) Common name(s) Source material(s)
Common name(s) Proper name(s) Part(s) Preparation

Gamma-Aminobutyric acid

  • GABA
  • gamma-Aminobutyric acid

  • Glutamic acid
  • GABA

Laminaria japonica

Whole

N/A

N/A

N/A

Synthetic

  • L-Theanine
  • N-Ethyl-L-glutamine

L-Theanine

L-Theanine

Camellia sinensis

Leaf

N/A

N/A

N/A

Synthetic

Group 8: Ingredients with adaptogen action

Proper name(s) Common name(s) Source material(s)
Proper name(s) Part(s) Preparation

Asparagus racemosus

  • Shatamuli
  • Shatavari

Asparagus racemosus

Root

Dried

Astragalus membranaceus

  • Astragalus
  • Huangqi
  • Huang qi
  • Membranaceus milk vetch
  • Membranous milk-vetch
  • Milk vetch root
  • Mo jia huang qi

Astragalus membranaceus

Root

Dried

Eleutherococcus senticosus

  • Ci wu jia
  • Eleuthero
  • Siberian ginseng

Eleutherococcus senticosus

  • Root
  • Root and rhizome
  • Root and stem bark

Dried

Ganoderma lucidum

  • Ganoderma
  • Ling zhi
  • Reishi

Ganoderma lucidum

  • Cultured mycelium
  • fruiting body
  • Mycelium

Dried

Glycyrrhiza glabra

  • Guang guo gan cao
  • Licorice
  • Liquorice

Glycyrrhiza glabra

  • Root
  • Root and stolon

Dried

Ocimum tenuiflorum

  • Holy basil
  • Rama tulsi
  • Sacred basil
  • Tulsi

Ocimum tenuiflorum

Leaf

Dried

Panax ginseng

  • Asian ginseng
  • Chinese ginseng
  • Hong shen
  • Korean ginseng
  • Korean red ginseng
  • Oriental ginseng
  • Panax ginseng
  • Red ginseng
  • Renshen

Panax ginseng

  • Root
  • Rootlet

Dried

Panax quinquefolius

  • American ginseng
  • Occidental ginseng
  • Sang
  • Shang
  • Xi yang shen

Panax quinquefolius

  • Root
  • Root and leaf

Dried

Rhodiola rosea

  • Hong jing tian
  • King's-crown
  • Rhodiola
  • Roseroot

Rhodiola rosea

  • Root
  • Root and rhizome

Dried

Schisandra chinensis

  • Chinese magnoliavine
  • Schisandra
  • Wu wei zi

Schisandra chinensis

Fruit

Dried

Tinospora cordifolia

Guduchi

Tinospora cordifolia

  • Stem
  • Stem and root
  • Stem, root and leaves

Dried

Withania somnifera

  • Asgandh
  • Ashwagandha
  • Asvagandha
  • Winter-cherry
  • Withania

Withania somnifera

  • Root
  • Whole plant

Dried

References: Proper names: NHPID 2019; Common names: NHPID 2019; Source materials: Group 1: Bone 2003; Hoffman 2003; Bradley 1992; Williamson et al. 1988; BHP 1983; Remington and Wood 1918; BPC 1911. Group 2: Hoffman 2003; Williamson et al. 1988. Group 3: Yurko-Mauro et al. 2010; Calabrese et al. 2008; Bone 2003; De Jesus Moreno Moreno 2003; Parnetti et al. 2001; Barbagallo et al. 1994; Parnetti et al. 1993; Canal et al. 1991. Group 4: EMA 2013; ESCOP 2009; Bradley 2006; Kennedy et al. 2004; Taylor 2003; Barnes et al. 2002; BHP 1983. Group 6: Bone 2003; API 2001. Group 7: Kanehira et al. 2011; Abdou et al. 2006; Yamakoshi et al. 2006. Group 8: Upton 2012; Winston and Kuhn 2008;Winston and Maimes 2007; WHO 2004; Bone 2003; Hoffman 2003; Thomsen 2002; Williamson 2002; Blumenthal et al. 2000; Upton 1999; WHO 1999; Bradley 1992; BHP 1983.

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

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 any age category listed in this monograph for the specified route of administration are listed in the Compendium of Monographs Guidance Document.

Use(s) or Purpose(s) and Dose(s)

Note
Claims for traditional use must include the term "Herbal Medicine", "Traditional Chinese Medicine", or "Ayurveda".

Subpopulation(s)

Adults 18 years and older

Quantity(ies)

Refer to Table 2. below.

Table 2. Cognitive function uses or purposes and associated daily doses
Uses or Purposes1 Medicinal Ingredients Methods of preparation Doses/day2

Group 1: Ingredients with nervine action

(Traditionally) used in Herbal Medicine to help relieve restlessness and/or nervousness (nervine/calmative)

Anemone pulsatilla(Pasqueflower)

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract)

0.03-0.6 grams dried herb top, per day

Non-Standardized 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

Matricaria chamomilla(German chamomile)

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)

1.5-24 grams dried flower, 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 Ayurveda to balance aggravated Vata (nervine)

Withania somnifera(Ashwagandha)

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)

2-6 grams dried root, per day

Group 2: Ingredients with calmative sedative action

(Traditionally) used in Herbal Medicine to help relieve restlessness and/or nervousness (calmative)
AND/OR
(Traditionally) used in Herbal Medicine as a sleep aid (during times of mental stress)

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

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

Passiflora incarnata(Passionflower)

Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)

0.25-8 grams dried herb top, per day

Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)

1-8 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

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

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

Standardized Extracts

0.3-12 grams of dried root/r root and rhizome, per day; Not to exceed 3.6 grams per single dose and:

  • 0.04-0.90% valerenic acid
    OR
  • 0.10-0.90% sesquiterpenic acids

(Traditionally) used in Herbal Medicine to help relieve restlessness and/or nervousness (calmative)
AND/OR
(Used in Herbal Medicine to) help(s) relieve sleep disturbances associated with mood imbalance

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

Standardized Extracts

600-1800 milligrams of 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

Used as a sleep aid/to help promote sleep

L-5-Hydroxytryptophan(L-5-HTP)

Isolate

100-200 milligrams, per day

Used as a sleep aid/to help promote sleep and/or helps 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

Standardized Extracts

0.3-12 grams of dried root/r root and rhizome, per day; Not to exceed 3.6 grams per single dose and:

  • 0.04-0.90% valerenic acid
    OR
  • 0.10-0.90% sesquiterpenic acids

Traditionally used in Ayurveda as a sleep aid and/or to balance aggravated Vata (nervine)

Withania somnifera (Ashwagandha)

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)

2-6 grams dried root, per day

Group 3: Ingredients with cognitive support action

Helps support cognitive health and/or brain function

Acetyl-L-Carnitine (Acetylcarnitine)

N/A

1.5-4 grams, per day

Bacopa monnieri (Bacopa)

Standardized Extracts

300 milligrams of extract, per day, standardized to 40-55% bacosides

Cod liver oil

Standardized fixed oil

18 years:
0.77-3.7 grams Cod liver oil, per day
And
100-1,258 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

19 years and older:
0.77-4 grams Cod liver oil, per day
And
100-1,360 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

18 years:
100-2,500 milligrams EPA and DHA including at least 100 milligrams DHA, per day

19 years and older:
100-5,000 milligrams EPA and DHA including at least 100 milligrams DHA, per day

Phosphatidylserine

N/A

300 milligrams, per day

Schizochytrium oil

Standardized fixed oil

200-2,000 milligrams DHA, per day

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

80-240 milligrams of extract, per day (50:1; quantity crude equivalent 4 - 12 g of dried leaves) and:

  • 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

Standardized Extracts

200-600 milligrams of extract, per day; standardized to 4-7% total ginsenosides; Not to exceed 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

Standardized Extracts

144-680 milligrams of extract, per day; Not to exceed 200 milligrams per single dose and:

  • 0.8 - 3% salidroside
    And/or
  • 1 - 6% rosavins

Group 4: Caffeine/Ingredients containing caffeine

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

Extract corresponding to a maximum Quantity Crude Equivalent of 6 grams dried leaf, per day and 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 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 corresponding to a Quantity Crude Equivalent of 3-6 grams dried leaf, per day and not exceeding 150 milligrams caffeine per day

Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)

Extract 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 corresponding to a Quantity Crude Equivalent of 1-3 grams dried seed, per day and not exceeding 200 milligrams caffeine per day

Group 5: Ingredient with action on cognitive fatigue

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

Group 6: Ingredients with action on memory

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

Withania somnifera(Ashwagandha)

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract, Decoction, Infusion)

2-6 grams dried root, per day

Helps support memory

Bacopa monnieri (Bacopa)

Standardized Extracts

300 mg of extract, per day, standardized to 40- 55% bacosides

Group 7: Ingredients with relaxation action

Helps to temporarily promote relaxation

Gamma-Aminobutyric acid (GABA)

N/A

50-3,000 milligrams, per day; Not to exceed 750 milligrams per single dose

L-Theanine

N/A

200-250 milligrams, per day

Group 8: Ingredients with adaptogen action

Used in Herbal Medicine as an Adaptogen to help increase energy and resistance to stress (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/root and stem bark, per day

Non-Standardized Aqueous Extracts (Dry extract, Decoction, Infusion)

2-3 grams dried root/root and rhizome/root and stem bark, per day

Ganoderma lucidum(Reishi)

Dry, Powder, Non-Standardized 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 40 % polysaccharides

Decoction

3-15 grams dried cultured mycelium/ fruiting body/mycelium, per day

Decoction Standardized

3-15 grams dried cultured mycelium/ fruiting body/mycelium, per day and 40 % polysaccharides

Glycyrrhiza glabra(Licorice)

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract)

0.6-6 grams dried root, per day

Ocimum tenuiflorum(Holy basil)

Dry, Powder, Non-Standardized Ethanolic Extracts (Dry extract, Tincture, Fluid extract)

2-3 grams dried leaf, per day

Non-Standardised Aqueous Extracts (Dry extract, Decoction, Infusion)

4.2-28 grams dried leaf, per day

Panax ginseng

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract)

0.5-3 grams dried root, per day

Non-Standardized Extracts (Dry extract, Decoction, Infusion)

0.5-2 grams dried root, per day

Panax quinquefolius (American ginseng)

Dry, Powder, Non-Standardized Extracts (Dry extract, Tincture, Fluid extract)

1-3 grams dried root, per day

Non-Standardized Extracts (Dry extract, Decoction, Infusion)

6-9 grams dried root, per day; Not to exceed 3 grams per single dose

Rhodiola rosea(Rhodiola)

Non-Standardised Dry Ethanolic Extracts

144-400 milligrams of 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 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

144-680 milligrams of 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

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/stem and root/stem and root and leaf, per day

Decoction

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 and 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-Standardised Dry Ethanolic Extracts

144-400 milligrams of 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 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

144-680 milligrams of 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

1References consulted for the uses or purposes: Group 1: Bone 2003; Hoffman 2003; Ellingwood 1983; Felter and Lloyd 1983; Grieve 1971. Group 2: Tobyn et al. 2010; Williamson et al. 1988. Group 3: Morgan and Stevens 2010; Yurko-Mauro et al. 2010; Calabrese et al. 2008; Malaguanera et al. 2008; De Jesus Moreno Moreno 2003; 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. Group 4: 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. Group 6: Barbhaiya et al. 2008; Stough et al. 2008; Raghav et al. 2006; Murthy 2004; Roodenrys et al. 2002; API 2001. Group 7: Kanehira et al. 2011; Abdou et al. 2006. Group 8: Upton 2012; Winston and Maimes 2007; Mills and Bone 2005; API 2004; WHO 2004; Bone 2003; Hoffman 2003; Thomsen 2002; Williamson 2002; Blumenthal et al. 2000; Upton 1999; WHO 1999; Bradley 1992;

2References consulted for the doses: Group 1: CNF 2012; Bone 2003; Hoffman 2003; Bradley 1992; Williamson et al. 1988; BHP 1983; Ellingwood 1983; Felter and Lloyd 1983; Remington and Wood 1918; BPC 1911. Group 2: Williamson et al. 1988. Group 3: 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; De Jesus Moreno Moreno 2003; 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. Group 4: Health Canada 2018; EMA 2013; Health Canada 2012; EMA 2010; ESCOP 2009; Bradley 2006; Taylor 2003. Group 6: Bone 2003; API 2001. Group 7: Kanehira et al. 2011; Powers et al. 2007; Yamakoshi et al. 2006. Group 8: Upton 2012; Winston and Maimes 2007; Mills and Bone 2005; API 2004; WHO 2004; Bone 2003; Hoffman 2003; Thomsen 2002; Williamson 2002; Blumenthal et al. 2000; Upton 1999; WHO 1999; Bradley 1992.

Direction(s) for use

See Table 4 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 Table 2.
  • 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.
  • Traditional with non-traditional use or purpose: When traditional and non-traditional claims are both made, the traditional claim must be preceded with the medicinal ingredient that supports it, unless it is a single medicinal ingredient product.
  • Combination of paradigms: When traditional Herbal Medicine and traditional Ayurvedic claims are both made, each claim must be preceded with the medicinal ingredient that supports it.
  • If products contain caffeine (Group 4), sedative/relaxation claims are not permitted.
  • If products contain sedatives (Group 2), alertness claims are not permitted.

Rules for Caffeine

  • The maximum amount of total caffeine permitted from all ingredients in the product is 400 mg/day, and 200 mg per single dose.
  • The maximum daily amount of caffeine permitted for each medicinal ingredient must be respected. Please see Table 2 above.
  • 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 100 mg/day, risk statements from the NNHPD Caffeine Monograph are required. Please see Table 4 below.
  • Additional synthetic caffeine added to Guarana and/or Yerba mate extracts must be represented as a separate medicinal ingredient.

Rules for sedatives

  • When combining L-5-HTP, St. John's Wort, and/or Passionflower, an additional risk statement is required. Please see Table 4 below.
  • If ingredients are combined within Group 2 (Ingredients with sedative action), the sum of the percentages of the maximum daily reference dose must not exceed 100%, for all ingredients contributing to support the claim. Please see Table 3 below.

Table 3. Combination Table to assess Safety of Group 2 Ingredients
Additive Indication Group 2 (e.g. Traditionally 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 Monograph 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%

Hypericum perforatum (St John's wort)

0.5 g

12.6 g

0.5/12.6 = 3.96%

Sum of percentages

87.3%

The calculations are performed as follows:

  • Percentage of the Maximum Daily Monograph 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 Monograph Reference Dose is 87.3%, which is less than 100%. Safety of the combination of ingredients is therefore supported.

Duration(s) of Use

See Table 4 below.

Risk Information

Consult Table 4 for appropriate statements related to each medicinal ingredient. The medicinal ingredients in Table 4 are associated with the required numbered statements below.

  1. As per the respective NNHPD monograph.
  2. Duration(s) of Use

  3. Ayurvedic bacopa claim only: Use for at least 6 weeks to see beneficial effects.
  4. Products providing 300 mg or more GABA per day: Consult a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 4 weeks.
  5. Caution(s) and warning(s)

  6. Consult a health care practitioner/health care provider/health care professional/doctor/ physician if symptoms persist or worsen.
  7. Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to use if you are pregnant or breastfeeding.
  8. Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to use if you are pregnant.
  9. Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to use if you are breastfeeding.
  10. Stop use if you experience severe stomach and/or intestinal irritation.
  11. Do not use if you have gastrointestinal irritation.
  12. Consult a health care practitioner/health care provider/health care professional/ doctor/ physician prior to use if you have a urinary tract disorder and/or kidney disease.
  13. Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to use if you have liver disease, kidney disease and/or a seizure disorder.
  14. Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to use if you have high blood pressure.
  15. Products providing 300 mg or more GABA per day: Do not use with alcohol.
  16. Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to use if you have glaucoma, and/or overactive bladder syndrome (detrusor instability).
  17. Avoid taking with health products or foods that contain caffeine and/or increase blood pressure (e.g. medications, coffee, tea, colas, cocoa, guarana, mate, bitter orange extract, synephrine, ocotopamine, ephedra, ephedrine ).
  18. This product is not intended as a substitute for sleep.
  19. Combination of ingredients resulting in a total caffeine content of more than 300 mg per day: Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are of childbearing age.
  20. Stop use and consult a health care practitioner/health care provider/health care professional/doctor/physician if you experience any of the following symptoms within a few hours after taking this product: changes in mental state such as restlessness or confusion, increased heart rate, enlarged pupils, loss of muscle coordination, sweating, shivering and/or gastrointestinal symptoms such as nausea, vomiting, diarrhea.
  21. Contraindication(s)

  22. Do not use this product if you are pregnant or breastfeeding.
  23. Do not use this product if you are pregnant.
  24. Known adverse reaction(s)

  25. May cause digestive problems.
Table 4. Risk information, durations of use, and directions for use associated with medicinal ingredients
Medicinal Ingredients Risk Information Durations of Use Directions for use2

1,3,7-trimethylxanthine (Caffeine)

1

Acetyl-L-Carnitine (Acetylcarnitine)

5, 11, 21

Asparagus racemosus (Shatavari)

6

Astragalus membranaceus (Astragalus)

1

Avena sativa (Oat)

4

Bacopa monnieri (Bacopa)

5, 21

2

Cod liver oil

1

Eleutherococcus senticosus (Eleuthero)

1

1

Eschscholzia californica (California poppy)

1

Fish oil

1

Gamma-Aminobutyric acid (GABA)

4, 5, 13

3

Ganoderma lucidum (Reishi)

1

1

1

Ginkgo biloba (Ginkgo)

1

1

Glycyrrhiza glabra (Licorice)

1

1

Humulus lupulus (Hops)

1

Hypericum perforatum (St. John's wort)

1

1

Ilex paraguariensis (Yerba mate)

5, 12

L-5-Hydroxytryptophan (L-5-HTP)

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

Paullinia cupana (Guarana)

5, 12

Phosphatidylserine

1

Anemone pulsatilla (Pasqueflower)

4, 8, 9, 10, 19

Rhodiola rosea (Rhodiola)

1

Schisandra chinensis (Schisandra)

7, 20

Scutellaria lateriflora (Skullcap)

1

Stachys officinalis (Wood Betony)

4, 5

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, 20

Valeriana officinalis (Valerian)

1

Withania somnifera (Ashwagandha)

1

Combination of ingredients resulting in a total caffeine content of 100 mg/day or more (e.g. Yerba mate and Guarana)

5, 12, 14, 15, 16, 17

Combination of two or more of the following ingredients: L-5-HTP, St John's Wort, and/or Passionflower

18

References consulted: EMA 2013; Gardner and McGuffin 2013; Fiebich et al. 2011; AMR 2010; Morgan and Stevens 2010; Okun et al. 2010; ESCOP 2009; Calabrese et al. 2008; CPS 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; FDA 2004; Nathan et al. 2004; Bone 2003; Erner et al. 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; Vahedi et al. 2000; Jee et al. 1999; Mester et al. 1995; Bradley 1992; Zimmerman 1992; Creighton and Stanton 1990; Rai et al. 1990; FDA 1988; 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

Products containing Cod liver oil, Fish oil or Schizochytrium oil

  • Refrigerate after opening (except when encapsulated) (Senanayake and Fichtali 2006; Wille and Gonus 1989).
  • Store in airtight container, protected from light (Ph.Eur. 2012; USP 35 2012).

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.

References Cited

  • Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors 2006; 26(3):201-8.
  • AMR 2010: Alternative Medicine Review (AMR). Acetyl-L-Carnitine Monograph. Alternative Medicine Review 2010; 15(1): 76-83.
  • API 2001: The Ayurvedic Pharmacopoeia of India, Part I, Volume II. Delhi (IN): The Controller of Publications; 2001.
  • API 2004: The Ayurvedic Pharmacopoeia of India, Part 1, Volume IV. Delhi (IN): The Controller of Publications; 2004.
  • Arya LA, Myers DL, Jackson ND. Dietary caffeine intake and the risk for detrusor instability: a case-control study. Obstetrics and Gynecology 2000; 96(1):85-89.
  • Avisar R, Avisar E, Weinberger D. Effect of coffee consumption on intraocular pressure. The Annals of Pharmacotherapy 2002; 36(6):992-995.
  • Bain MA, Faull R, Fornasini G. Accumulation of trimethylamine and trimethylamine-N-oxide in
  • end-stage renal disease patients undergoing haemodialysis. Molecular Genetics and Metabolism 2004; 81:263-272.
  • Barbagallo SG, Barbagallo M, Giordano M, Meli M, Panzarasa R. Alpha-glycerophosphocholine in mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Annals of the New York Academy of Science 1994; 717: 253-269.
  • Barbhaiya C, Desai R, Saxena V, Pravina K, Wasim P, Geetharani P, Allan J, Venkateshwarlu K, Amit A. Efficacy and tolerability of bacomind® on memory improvement in elderly participants- A double blind placebo controlled study. Journal of Pharmacology and Toxicology 2008; 3(6): 425-434.
  • Barnes J, Anderson LA, Philipson JD. Herbal Medicines: A Guide for Healthcare Professionals, 2nd edition. London (GB): The Pharmaceutical Press; 2002.
  • Berardi RR, DeSimone EM, Newton GD, Oszko MA, Popovich NG, Rollins CJ, Shimp LA, Tietze KJ, editors. Handbook of Non-prescription Drugs: An Interactive Approach to Self-Care, 13th edition. Washington (DC): American Pharmaceutical Association; 2002.
  • BHP 1983: British Herbal Pharmacopoeia. Cowling (GB): British Herbal Medical Association; 1983.
  • Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine: Expanded Commission E Monographs. American Botanical Council; 2000.
  • Bone K. A clinical guide to blending liquid herbs: Herbal formulations for the individual patient. St. Louis (MI): Churchill Livingstone; 2003.
  • Bouchard NC, Howland MA, Greller HA, Hoffman RS, Nelson LS. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clinic Proceeding 2005; 80(4):541-545.
  • BPC 1911: British Pharmaceutical Codex. Council of the Pharmaceutical Society of Great Britain; 1911.
  • Bradley PR, editor. British Herbal Compendium: A Handbook of Scientific Information on
  • Widely Used Plant Drugs, Volume 1. Bournemouth (GB): British Herbal Medicine Association; 1992.
  • Bradley PR, editor. British Herbal Compendium: A Handbook of Scientific Information on
  • Widely Used Plant Drugs, Volume 2. Bournemouth (GB): British Herbal Medicine Association; 2006.
  • Brinker F. Herb Contraindications and Drug Interactions, 3rd edition. Sandy (OR): Eclectic Medical Publications; 2001.
  • Brinker F. 2010. Online Updates and Additions to Herb Contraindications and Drug Interactions, 3rd edition. Sandy (OR): Eclectic Medical Publications; 2010. [Accessed 2014-03-04]. Available from: http://www.eclecticherb.com/emp/updatesHCDI.html.
  • Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. The Annals of Pharmacotherapy 2006; 40(1):53-57.
  • Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, and Oken B. Effects of a standardized
  • Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: A randomized, double-blind, placebo-controlled trial. The Journal of Alternative and Complimentary Medicine 2008; 14(6): 707-713.
  • Canal N, Franceschi M, Alberoni M, Castiglioni C, De Moliner P, Longoni A. Effects of L- alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine. International Journal of Clinical Pharmacology. Therapy and Toxicology 1991; 29(3): 103-107.
  • Chandrasekaran S, Rochtchina E, Mitchell P. Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study. Journal of Glaucoma 2005;14(6):504-507.
  • Christopher G, Sutherland D, Smith A. Effects of caffeine in non-withdrawn volunteers. Human Psychopharmacology 2005;20(1):47-53.
  • CNF 2012: Canadian Nutrient File (CNF). Nutrition & Healthy Eating, Food and Nutrition, Health Canada. [Accessed 2014-03-26]. Available from: http://webprod3.hc-sc.gc.ca/cnf- fce/index-eng.jsp.
  • Cornelis MC, El-Sohemy A. Coffee, caffeine, and coronary heart disease. Current Opinion in Lipidology 2007;18(1):13-19.
  • CPS 2008: Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals. Ottawa (ON): Canadian Pharmacists Association; 2008.
  • Creighton SM, Stanton SL. Caffeine: does it affect your bladder? British Journal of Urology 1990;66(6):613-614.
  • De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: A multicenter, double-blind, randomized, placebo-controlled trial. Clinical Therapeutics 2003; 25(1): 178-193.
  • Ellingwood F. 1983. American Materia Medica, Therapeutics and Pharmacognosy. Sandy (OR): Eclectic Medical Publications [Reprint of 1919 original].
  • EMA 2010: European Medicines Agency. Community herbal monograph on Ilex paraguariensis St. Hilaire, folium. London (UK): Committee on Herbal Medicinal Products (HMPC); 2009.
  • [Accessed 29 May 2017]. Available from:
  • http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-
  • _Community_herbal_monograph/2010/01/WC500059234.pdf.
  • EMA 2013: European Medicines Agency. Community herbal monograph on Paullinia cupana Kunth ex H.B.K. var. sorbilis (Mart.) Ducke, semen. London (UK): Committee on Herbal
  • Medicinal Products (HMPC); 2013. [Accessed 29 May 2017]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-
  • _Community_herbal_monograph/2013/03/WC500140768.pdf.
  • Erner RA, Meglathery SB, Van Decker WA, Gallagher RM. Seratonin Syndrome and Other Serotonergic Disorders. Pain Medicine 2003; 4(1): 63-74.
  • ESCOP 2009: European Scientific Cooperative on Phytotherapy. ESCOP Monographs: The Scientific Foundation for Herbal Medicinal Products, 2nd edition, Supplement 2009. Exeter (GB): European Scientific Cooperative on Phytotherapy in collaboration with Thieme.
  • FDA 1988: Food and Drug Administration. 21 CFR Part 340. Stimulant drug products for over- the-counter human use; final monograph; final rule. Washington (DC): U.S. Food and Drug Administration, Department of Health and Human Services; 1988. [Accessed 2007-05-30]. Available from: http://ecfr.gpoaccess.gov/cgi/t/text/text- idx?c=ecfr&tpl=/ecfrbrowse/Title21/21cfr340_main_02.tpl.
  • FDA 2004: Food and Drug Administration. Sales of supplements containing ephedrine alkaloids (ephedra) prohibited. Washington (DC): Food and Drug Administration, US Department of
  • Health and Human Services; 2004. [Accessed 2007-04-13]. Available from: http://www.fda.gov/oc/initiatives/ephedra/february2004/.
  • Felter HW, Lloyd JU. King's American Dispensatory, Volume 1, 18th edition. Sandy (OR): Eclectic Medical Publications; 1983 [Reprint of 1898 original].
  • Fiebich BL, Knorle R, Appel K, Kammler T, Weiss G. Pharmacological studies in an herbal drug combination of St. John's Wort (Hypericum perforatum) and passion flower (Passiflora
  • incarnata): In vitro and in vivo evidence of synergy between Hypericum and Passiflora in antidepressant pharmacological models 2011; 82: 474-480.
  • Gardner Z and McGuffin M, editors. 2013. American Herbal Products Association's Botanical Safety Handbook Second Edition. Boca Raton (FL): CRC Press.
  • Grieve M. 1971. A Modern Herbal, Volume 1. New York (NY): Dover Publications [Reprint of 1931 Harcourt, Brace & Company publication].
  • Haller CA, Benowitz NL, Jacob P. Hemodynamic effects of ephedra-free weight-loss supplements in humans. The American Journal of Medicine 2005;118(9):998-1003.
  • Health Canada 2018. Caffeine monograph. Natural and Non-Prescription Health Products Directorate. Ottawa (ON). [Accessed 2019-02-14]. Available from: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=caffeine.cafeine&lang=eng
  • Health Canada 2012. Caffeine in foods. Health Canada. [Accessed 2019-02-14]. Available from: https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/food-additives/caffeine-foods/foods.html
  • Hoffmann D. Medical Herbalism: The Science and Practice of Herbal Medicine. Rochester (VT): Healing Arts Press; 2003.
  • Jee SH, He J, Whelton PK, Suh II, Klag MJ. The effect of chronic coffee drinking on blood pressure: a meta-analysis of controlled clinical trials. Hypertension 1999;33(2):647-652.
  • Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. Journal of Clinical Psychiatry 1988;49(2):72-73.
  • Jensen CL Voigt RG, Llorente AM, Peters SU, Prager TC, Zou YL, Rozelle JC, Turchich, MR, Frayley JK, Anerson RE, Heird WC. Effects of early maternal docosahexaenoic acid intake on
  • neuropsychological status and visual acuity at five years of age of breast-fed term infants. The Journal of Pediatrics 2010; 125:900-905.
  • Kamimori GH, Penetar DM, Headley DB, Thorne DR, Otterstetter R, Belenky G. Effect of three caffeine doses on plasma catecholamines and alertness during prolonged wakefulness. European Journal of Clinical Pharmacology 2000;56(8):537-544.
  • Kanehira T, Nakamura Y, Nakamura K, Horie K, Horie N, Furugori K, Sauchi Y, Yokogoshi H. Relieving Occupational Fatigue by Consumption of a Beverage Containing gamma-Amino
  • Butyric Acid. Journal of Nutritional Science and Vitaminology 2011; 57(1):9-15.
  • Kennedy DO, Haskell CF, Wesnes KA, Scholey AB (2004). Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison
  • and interaction with Panaxginseng. Pharmacology, Biochemistry, and Behaviour 2004; 79(3):401-411.
  • Malaguarnera M, Gargate, MP, Cristaldi E, Colonna V, Messano M, Koverech A, Neri S, Vacante M, Cammalleri L, Motta, M. Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Archives of Gerontology and Geriatrics 2008; 46: 181-190.
  • Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A. Caffeine withdrawal increases lithium blood levels. Biological Psychiatry 1995;37(5):348-350.
  • Mills E, Dugoua JJ, Perri D, Koren G. Herbal Medicines in Pregnancy and Lactation.Boca Raton (FL):Taylor and Francis Medical; 2006.
  • Mills S and Bone K. The Essential Guide to Herbal Safety. St. Louis (MO): Elsevier Churchill Livingstone; 2005.
  • Morgan and Stevens. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. The Journal of Alternative and Complementary Medicine 2010; 16 (7): 753-759.
  • Murthy KRS. Bhavaprakasha of Bhavmisra, Volume 1. Varanasi (IND): Chowkhamba Krishnadas Academy; 2004.
  • Nathan PJ, Clarke, J, Lloyd J, Hutchison CW, Downey L, Stough C. The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects. Human Psychopharmacology 2001; 16:345-351.
  • Nathan PJ, Tanner S, Lloyd J, Harrison B, Curran, L, Oliver C, Stough C. Effects of a combined extract of Ginkgo biloba and Bacopa monniera on cognitive function in healthy humans. Human Psychopharmacology 2004; 19(2):91-96.
  • NHPID 2019. Natural Health Products Ingredients Database. [Accessed 2019-02-14]. Available from: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/search-rechercheReq.do
  • Noordzij M, Uiterwaal CS, Arends LR, Kok FJ, Grobbee DE, Geleijnse JM. Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. Journal of Hypertension 2005;23(5):921-928.
  • Okun MS, Boothby LA, Bartfield RB, Doering PL. GHB: an important pharmacologic and
  • clinical update. Journal of Pharmacy & Pharmaceutical Sciences: A Publication of the Canadian
  • Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques. 2001; 4(2):167-175.
  • Parnetti L, Abate G, Bartorelli L, Cucinotta D, Cuzzupoli M, Maggioni M, Villardita C, Senin U.
  • Multicentre study of l-?-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer's type. Drugs and Aging 1993; 3(2): 159-164.
  • Parnetti L, Amenta F, and Gallai, V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mechanisms of Ageing and Development 2001; 122:2041-2055.
  • Pettegrew JA, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. Clinical and neurochemical effects of acetyl-l-carnitine in Alzheimer's disease. Neurobiology of Aging 1994; 16(1):1-4.
  • Ph.Eur. 2012: European Pharmacopoeia, 8th edition. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM); 2012.
  • Powers ME, Yarrow JF, McCoy SC, Borst SE. Growth Hormone Isoform Responses to GABA Ingestion at Rest and after Exercise. Medicine & Science in Sports & Exercise 2007; 40(1):104- 110.
  • Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer's disease. Journal of the American Medical Association 2010; 304(17): 1903-1911.
  • Raghav S, Singh H, Dalal P, Srivastava J, Asthana O. Randomized controlled trial of
  • standardized Bacopa monniera extract in age-associated memory impairment. Indian Journal of Psychiatry 2006; 48(4): 238-242.
  • Rai G, Wright G, Scott L, Beston B, Rest J, Exton-Smith AN. Double-blind, placebo controlled study of acetyl-L-carnitine in patients with Alzheimer's dementia. Current Medical Research Opinion 1990; 11:638-647.
  • Remington JP and Woods HC, editors. The Dispensatory of the United States of America, 20th edition; 1918.
  • Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology 2002; 27(2):279-81.
  • Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux
  • R. Double blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Archive of Neurology 1992; 49 (11): 1137-1141.
  • Senanayake SPJN, Fichtali J. Single-cell oils as sources of nutraceutical and specialty lipids: processing technologies and applications. In: Shahidi F, editor. Neutraceutical and speciality lipids and their co-products. Boca Raton (FL): Taylor and Francis Group; 2006.
  • Shils ME, Olson JA, Shike M, Ross AC, editors. Modern Nutrition in Health and Disease, 10th edition. Philadelphia (PA): Lippincott Williams and Wilkins; 2006.
  • Spagnoli A, Lucca U, Menasce, Bandera L, Cizza G, Forloni G, Tettamanti M, Frattura L, Tiraboschi P, Comelli M, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology 1991; 41(11):1726-1732.
  • Stough C, Downey L, Lloyd J, Silber B, Redman S, Hutchison C, Wesnes K, Nathan P. Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial. Phytotherapy Research 2008; 22(12):1629-34.
  • Stough C, Lloyd J, Clarke J, Downey L, Hutchison CW, Rodgers T, Nathan PJ. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human
  • subjects. Psychopharmacology 2001; 156(4): 481-484
  • Taylor L. Technical data report for Yerba mate: Reprinted from Herbal Secrets of the Rainforest, 2nd Edition. Sage Press Inc.; 2003.
  • Thal LJ, Calvani M, Amato A, Carta AA. 1-year controlled trial of acetyl-L-carnitine in early- onset AD. Neurology 2000; 55: 805-810.
  • Thomsen M. Shatavari-Asparagus racemosus, Herbal Monograph, Phytomedicine. NSW Australia; 2002.
  • Tobyn G, Denham A, Vhitelegg M. The Western Herbal Tradition: 2000 years of medicinal plant knowledge. Churchill-Livingstone; 2010.
  • Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacology & Therapeutics 2006;109(3):325-338.
  • Upton R, editor. American Herbal Pharmacopoeia and Therapeutic Compendium: American Ginseng Root (Panax quinquefolius L.)-Standards of Analysis, Quality Control, and
  • Therapeutics. Santa Cruz (CA): American Herbal Pharmacopeia; 2012.
  • Upton R, editor. American Herbal Pharmacopoeia and Therapeutic Compendium: Schisandra Berry (Schisandra chinensis)-Analytical, Quality Control, and Therapeutic Monograph. Santa Cruz (CA): American Herbal Pharmacopoeia; 1999.
  • USP 35 2012: United States Pharmacopeia and the National Formulary (USP 35 - NF 30). Rockville (MD): The United States Pharmacopeial Convention; 2012.
  • Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischaemic stroke in a sportsman who
  • consumed MaHuang extract and creatine monohydrate for body building. Journal of Neurology, Neurosurgery and Psychiatry 2000;68(1):112-113.
  • Wille HJ, Gonus P. Preparation of Fish Oil for Dietary Applications. In: Galli C, Simopolous AP, editors. Dietary ?3 and ?6 Fatty Acids. Biological Effects and Nutritional Essentiality. New York (NY): Plenum Press; 1989.
  • Williamson EM, editor. Major Herbs of Ayurveda. Edinburgh (GB): Churchill Livingstone; 2002
  • Williamson EM, Evans FJ, Wren RC. Potter's New Cyclopaedia of Botanical Drugs and
  • Preparations. Saffron Walden (GB): C.W. Daniel Company Limited; 1988.
  • Winston D, Maimes S. Adaptogens: Herbs for strength, stamina and stress relief. Rochester (VT): Healing Arts Press; 2007.
  • Winston D and Kuhn MA. Herbal Therapy and Supplements: A Scientific and Traditional
  • Approach. Philadelphia (PA): Wolters Kluwer Health and Lippincott Williams & Wilkins; 2008.
  • WHO: World Health Organization. WHO monographs on selected medicinal plants 2004; Volume 2.
  • WHO: World Health Organization. WHO monographs on selected medicinal plants 1999; Volume 1.
  • Yamakoshi J, Shiojo R, Nakagawa S, Izui N, Ogihaara T. Hypotensive Effects and Safety of Less-salt Soy Sauce Containing gamma-aminobutyric acid (GABA) on High-Normal Blood Pressure and Mild Hypertensive Subjects. Yakuri To Chirya 2006; 34:691-709 [English Translation].
  • Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N, Stedman
  • M. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline, Alzheimer's and Dementia 2010; 6:1-9.
  • Zimmerman DR. Zimmerman's Complete Guide to Non-prescription Drugs, 2nd edition. Detroit (MI): Gale Research Inc.; 1992.
  • Zwickey H, Brush J, Iacullo CM, Connelly E, Gregory WL, Soumyanath A, Buresh R. The effect of Echinacea purpurea, astragalus membranaceus and Glycyrrhiza glabra on CD25 Expression in Humans: A Pilot Study. Phytotherapy Research 2007; 21(11): 1109-1112.
  • Zwyghuizen-Doorenbos A, Roehrs TA, Lipschutz L, Timms V, Roth T. Effects of caffeine on alertness. Psychopharmacology 1990; 100(1):36-39.

References Reviewed

  • Blumenthal M, Busse W, Goldberg A, Gruenwald, J, Hall T, Riggins C, Rister R. The complete German Commission E monographs. Austin, TX: American Botanical Council; 1998.
  • Brinker F. The Toxicology of Botanical Medicines. Sandy (OR): Eclectic Medical Publications; 2000.
  • Calvani, M., Carta, A., Benedetti, N., Iannuccelli, M., Caruso, G. Action of acetyl-L-carnitine in neurodegeneration and Alzheimer's disease. Aging and Cellular Defense Mechanisms 1992; 663:483-486.
  • Gogte VVM. Ayurvedic Pharmacology and Therapeutic Uses of Medicinal Plants. Mubai (IN): Bharatiya Vidya Bhavan; 2000.
  • Rege NN, Thatte UM, and Dahanukar SA. Adaptogenic properties of sixrasayana herbs used in Ayurvedic medicine. Phytotherapy Research 1999; 13(4):275-291.
  • Sayre, L. A Manual of Organic Materia Medica and Pharmacognosy. P. Blakiston's Son & Company; 1917.
  • Upton R, editor. American Herbal Pharmacopoeia and Therapeutic Compendium: Astragalus Root (Astragalus membranaceus & Astragalus membranaceus var. mongolicus)-Analytical, Quality Control, and Therapeutic Monograph. Santa Cruz (CA): American Herbal
  • Pharmacopoeia; 1999.
  • Wilson L. Review of adaptogenic mechanisms: Eleutherococcus senticosus, Panaxginseng, Rhodiola rosea, Schisandra chinensis and Withania somnifera. Australian Journal of Medical Herbalism 2007; 19(3): 126-131.
  • Zwickey H, Brush J, Iacullo CM, Connelly E, Gregory WL, Soumyanath A, Buresh R. The effect of Echinacea purpurea, astragalus membranaceus and Glycyrrhiza glabra on CD25 Expression in Humans: A Pilot Study. Phytotherapy Research 2007; 21(11): 1109-1112.