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Title:
METHODS OF IMPROVING MENTAL OR HEALTH CONDITIONS
Document Type and Number:
WIPO Patent Application WO/2013/164402
Kind Code:
A1
Abstract:
Methods of improving mental or health conditions of an individual are provided. In a general embodiment, the method provides administering to an individual in need of an improved mental or health condition a decaffeinated coffee product. The methods can be, for example, for improved alertness in the individual, improved attention, improved reaction time, reduction in the individual's jitteriness, tension, tiredness, mental fatigue and/or headache.

Inventors:
SILBER YVONNE BEATA (CH)
SCHMITT JEROEN ANTONIUS JOHANNES (CH)
Application Number:
PCT/EP2013/059141
Publication Date:
November 07, 2013
Filing Date:
May 02, 2013
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
NESTEC SA (CH)
International Classes:
A23F5/02; A61K31/216; A61K36/185
Domestic Patent References:
WO2003037098A12003-05-08
WO2009132889A12009-11-05
WO2012062928A12012-05-18
Foreign References:
EP1712137A12006-10-18
EP1078576A12001-02-28
EP0916267A21999-05-19
Other References:
DATABASE WPI Week 201104, Derwent World Patents Index; AN 2010-L20458, XP002627374
KWON S H ET AL: "Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice", EUROPEAN JOURNAL OF PHARMACOLOGY, ELSEVIER BV, NL, vol. 649, no. 1-3, 18 September 2010 (2010-09-18), pages 210 - 217, XP027451062, ISSN: 0014-2999, [retrieved on 20100918]
CHU YI-FANG ET AL: "Roasted coffees high in lipophilic antioxidants and chlorogenic acid lactones are more neuroprotective than green coffees.", 28 October 2009, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 28 OCT 2009 LNKD- PUBMED:19772322, VOL. 57, NR. 20, PAGE(S) 9801 - 9808, ISSN: 1520-5118, XP002626921
FARAH ADRIANA ET AL: "Effect of roasting on the formation of chlorogenic acid lactones in coffee", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 53, no. 5, 9 March 2005 (2005-03-09), pages 1505 - 1513, XP002527704, ISSN: 0021-8561, [retrieved on 20050210], DOI: DOI:10.1021/JF048701T
CROPLEY VANESSA ET AL: "Does coffee enriched with chlorogenic acids improve mood and cognition after acute administration in healthy elderly? A pilot study.", February 2012, PSYCHOPHARMACOLOGY FEB 2012 LNKD- PUBMED:21773723, VOL. 219, NR. 3, PAGE(S) 737 - 749, ISSN: 1432-2072, XP002684034
Attorney, Agent or Firm:
ELLEBY, Gudrun (Avenue Nestlé 55, Vevey, CH)
Download PDF:
Claims:
CLAIMS

The invention is claimed as follows:

1. A method of improving alertness, improving attention, reducing tension, and/or reducing mental fatigue in an individual for at least 1 hour, the method comprising:

administering to an individual in need of improved alertness, improved attention, reduced tension, and/or reduced mental fatigue a decaffeinated coffee product to improve alertness, improve attention, reduce tension, and/or reduce mental fatigue in the individual.

2. The method of Claim 1, wherein the decaffeinated coffee product has a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

3. The method of any one of Claims 1 to 2, wherein the decaffeinated coffee product comprises a mixture of unroasted coffee and roasted coffee.

4. The method of any one of Claims 1 to 3, wherein the decaffeinated coffee product comprises an extract of unroasted coffee.

5. The method of Claim 4, wherein the extract is derived from:

(i) a first portion comprising unroasted ground and/or unground coffee, in an amount of from 1 to 90% by weight based on the total weight of the coffee product, and

(ii) a second portion comprising ground coffee that has been roasted to a higher degree of roast than the first portion, in an amount of from 99 to 10% by weight based on the total weight of the coffee product, wherein the content of the chlorogenic acids is at least 4 g per 100 g of the coffee product.

6. A method of improving reaction time, reducing tiredness and/or reducing jitteriness in an individual, the method comprising: administering to an individual in need of improved reaction time, reduced tiredness and/or reduced jitteriness a decaffeinated coffee product to improve reaction time, reduce tiredness and/or reduce jitteriness in the individual.

7. The method of Claim 6, wherein the decaffeinated coffee product has a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

8. The method of any one of Claims 6 to 7, wherein the decaffeinated coffee product comprises a mixture of unroasted coffee and roasted coffee.

9. The method of any one of Claims 6 to 8, wherein the decaffeinated coffee product comprises an extract of unroasted coffee.

10. The method of Claim 9, wherein the extract is derived from:

(i) a first portion comprising unroasted ground and/or unground coffee, in an amount of from 1 to 90% by weight based on the total weight of the coffee product, and

(ii) a second portion comprising ground coffee that has been roasted to a higher degree of roast than the first portion, in an amount of from 99 to 10% by weight based on the total weight of the coffee product, wherein the content of the chlorogenic acids is at least 4 g per 100 g of the coffee product.

11. A method of reducing headache for at least 1 hour in an individual, the method comprising:

administering to an individual in need of reduced headache a decaffeinated coffee product to reduce headache in the individual.

12. The method of Claim 11, wherein the decaffeinated coffee product has a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

13. The method of any one of Claims 11 to 12, wherein the decaffeinated coffee product comprises a mixture of unroasted coffee and roasted coffee.

14. The method of any one of Claims 11 to 13, wherein the decaffeinated coffee product comprises an extract of an unroasted coffee.

15. The method of Claim 14, wherein the extract is derived from:

(i) a first portion comprising unroasted ground and/or unground coffee, in an amount of from 1 to 90% by weight based on the total weight of the coffee product, and

(ii) a second portion comprising ground coffee that has been roasted to a higher degree of roast than the first portion, in an amount of from 99 to 10% by weight based on the total weight of the coffee product, wherein the content of the chlorogenic acids is at least 4 g per 100 g of the coffee product.

16. A method of improving alertness in an individual for at least 1 hour, the method comprising:

administering to an individual in need of improved alertness a non-coffee product comprising a component selected from the group consisting of a decaffeinated coffee extract, chlorogenic acids and combinations thereof to improve alertness in the individual.

17. The method of Claim 21 , wherein the chlorogenic acids are derived from a food source.

18. A method of reducing jitteriness in an individual, the method comprising: administering to an individual in need of reduced jitteriness a non-coffee product comprising a component selected from the group consisting of a decaffeinated coffee extract, chlorogenic acids and combinations thereof to reduce jitteriness of the individual.

19. The method of Claim 23, wherein the chlorogenic acids are derived from a food source.

20. A method of reducing headache for at least 1 hour in an individual, the method comprising:

administering to an individual in need of reduced headache a non-coffee product comprising a component selected from the group consisting of a decaffeinated coffee extract, chlorogenic acids and combinations thereof to reduce headache of the individual.

21. The method of Claim 25, wherein the chlorogenic acids are derived from a food source.

22. The use of a decaffeinated coffee product to improve alertness, improve attention, reduce tension, and/or reduce mental fatigue in an individual for at least 1 hour.

23. The use of claim 22 wherein the decaffeinated coffee product comprises an extract of unroasted coffee.

24. The use of a decaffeinated coffee product to reduce tiredness, improve reaction time and/or reduce jitteriness in an individual.

25. The use of claim 24 wherein the decaffeinated coffee product comprises an extract of unroasted coffee.

26. The use of chlorogenic acids to reduce jitteriness in an individual.

27. The use of chlorogenic acids to reduce headache in an individual for at least 1 hour.

28. The use of chlorogenic acids to reducetiredness in an individual for at least 1 hour.

Description:
METHODS OF IMPROVING MENTAL OR HEALTH CONDITIONS

BACKGROUND

[0001] The present disclosure generally relates to methods for improving mental or physical health conditions of an individual. More specifically, the present disclosure relates to methods of improving attention, alertness, and/or reaction times, and methods of reducing jitteriness, tension, tiredness, mental fatigue, and/or headaches of an individual.

[0002] Coffee is a complex mixture of many hundreds of compounds, which, in combination, form a unique and pleasing aroma and taste desired by many consumers. Furthermore, coffee is consumed not only for its desirable flavor but often for other reasons, such as to increase short term mental alertness. The positive health impact of coffee has been studied over many decades and, for a long time, it has been known that certain coffee compounds are capable of providing benefits to the consumer, especially increased mental alertness through the ingestion of caffeine. However, it is less well known to consumers that certain coffee compounds are excellent anti-oxidants and that, weight for weight, coffee can potentially provide significantly more antioxidants to the consumer than, for example, a well known source of antioxidants such as green tea.

[0003] A very important source of antioxidants that has been identified in coffee is the class known as chlorogenic acids. Chlorogenic acids ("CGA") in coffee are mainly mono- and di-esters of quinic acid and phenolic groups (e.g., caffeic, ferulic, coumaric, methoxycinnamic) attached to different positions. In vitro studies have confirmed the antioxidant properties of CGA, which prevents oxidation by chelating metals and scavenging reactive oxygen species. In addition to its antioxidant effects, rodent models have also shown CGA compounds to have anxiolytic, anti-inflammatory, analgesic and antipyretic effects, weak caffeine-like psychostimulant actions on spontaneous locomotor activity. A distinct neuroprotective action of CGA compounds is also evidenced by its ability to protect neuronal cells from beta-amyloid-induced toxicity and oxidative stress.

[0004] From the health and nutritional perspective, it is desirable that consumers should be able to benefit from the positive health aspects of coffee identified above and so it would be highly advantageous to utilize the beneficial components of coffee such as chlorogenic acids. However, few studies have been performed to show the impact these beneficial components on a variety of mental and physical health conditions of an individual. SUMMARY

[0005] The present disclosure provides methods for improving the mental or health conditions in an individual. In an embodiment, the present disclosure provides a method of improving alertness, improving attention, reducing tension, and/or reducing mental fatigue in an individual for at least 1 hour, the method comprising: administering to an individual in need of improved alertness, improved attention, reduced tension, and/or reduced mental fatigue a decaffeinated coffee product to improve alertness, improve attention, reduce tension, and/or reduce mental fatigue in the individual. The decaffeinated coffee product can have a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

[0006] In another embodiment, the present disclosure provides a method of improving reaction time, reducing tiredness and/or reducing jitteriness in an individual, the method comprising: administering to an individual in need of improved reaction time, reduced tiredness and/or reduced jitteriness a decaffeinated coffee product to improve reaction time, reduce tiredness and/or reduce jitteriness in the individual. The decaffeinated coffee product can have a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

[0007] In an alternative embodiment, the present disclosure provides a method of reducing headache for at least 1 hour in an individual, the method comprising: administering to an individual in need of reduced headache a decaffeinated coffee product to reduce headache in the individual. The decaffeinated coffee product can have a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

[0008] In any of the methods described herein, the decaffeinated coffee product may include a mixture of unroasted coffee and roasted coffee. In any of the methods described herein, the unroasted coffee may be in the form of an extract of an unroasted coffee. For example, the extract can be derived from (i) a first portion including unroasted ground and/or unground coffee, in an amount of from 1 to 90% by weight based on the total weight of the coffee product, and (ii) a second portion including ground coffee that has been roasted to a higher degree of roast than the first portion, in an amount of from 99 to 10% by weight based on the total weight of the coffee product, wherein the content of the chlorogenic acids is at least 4 g per 100 g of the coffee product. [0009] In yet another embodiment, the present disclosure provides a method of improving alertness in an individual for at least 1 hour, the method comprising: administering to an individual in need of improved alertness a non-coffee product comprising a component selected from the group consisting of an unroasted coffee extract, chlorogenic acids and combinations thereof to improve alertness in the individual.

[0010] In still another embodiment, the present disclosure provides a method of reducing jitteriness in an individual, the method comprising: administering to an individual in need of reduced jitteriness a non-coffee product comprising a component selected from the group consisting of an unroasted coffee extract, chlorogenic acids and combinations thereof to reduce jitteriness of the individual.

[0011] In another embodiment, the present disclosure provides a method of reducing headache for at least 1 hour in an individual, the method comprising: administering to an individual in need of reduced headache a non-coffee product comprising a component selected from the group consisting of an unroasted coffee extract, chlorogenic acids and combinations thereof to reduce headache of the individual.

[0012] In any of the methods herein, the chlorogenic acids can be derived from a food source (including coffee). The non-coffee product can be a food product, a beverage, a food supplement, a pet care product, a pharmaceutical product or a combination thereof.

[0013] In an embodiment, the present disclosure provides the use of a decaffeinated coffee product to improve alertness, improve attention, reduce tension, and/or reduce mental fatigue in an individual for at least 1 hour. In another embodiment, the present disclosure provides the use of a decaffeinated coffee product to reduce tiredness, improve reaction time, and/or reduce jitteriness in an individual. In yet another embodiment, the present disclosure provides the use of chlorogenic acids to reduce jitteriness in an individual. In yet another embodiment, the present disclosure provides the use of chlorogenic acids to reduce headache in an individual for at least 1 hour. In yet another embodiment, the present disclosure provides the use of chlorogenic acids to reduce tiredness in an individual for at least 1 hour.

[0014] An advantage of the present disclosure is to provide a method of improving a mental condition of an individual using a decaffeinated coffee product.

[0015] Another advantage of the present disclosure is to provide a method of improving a health condition of an individual using a decaffeinated coffee product.

[0016] Still another advantage of the present disclosure is to provide a method of improving a mental or health condition of an individual using chlorogenic acids. [0017] Yet another advantage of the present disclosure is to provide a method of improving the alertness, and/or reducing jitteriness, tension, tiredness, headache and/or mental fatigue of an individual using an extract from a coffee product.

[0018] Additional features and advantages are described herein, and will be apparent from, the following Detailed Description.

DETAILED DESCRIPTION

[0019] The present disclosure relates generally to methods for improving the mental and/or health conditions of an individual. In a general embodiment, the method provides administering to an individual in need of an improved mental or health condition a decaffeinated coffee product. The decaffeinated coffee product can include portions of an unroasted and a roasted coffee in any suitable form.

[0020] Without being bound by theory, it has been surprisingly found that providing individuals with components of a decaffeinated coffee product can improve various mental and health conditions in an individual. The mental or health condition can be, for example, improved alertness in the individual, improved attention, improved reaction time, reduced jitteriness, reduced tension, reduced tiredness, reduced headache and/or reduced mental fatigue. These improved mental or health conditions can include those not normally attributable to caffeine typically found in coffee products.

[0021] As used herein, the term "alertness" refers to the state of paying close and continuous attention, being watchful and prompt, or being quick to perceive and/or act. It is being vigilantly attentive, mentally responsive and perceptive, and quick.

[0022] As used herein, the term "reaction time" refers to the elapsed time between the onset of a stimulus and the detection of a response to the stimulus.

[0023] As used herein, the term "jitteriness" refers to feeling nervous or uneasy. Can be marked by jittering movements.

[0024] As used herein, the term "tension" refers to mental, emotional, or nervous strain.

[0025] As used herein, the term "tiredness" refers to exhausted of strength and/or energy; fatigued or sleepy.

[0026] As used herein, the term "mental fatigue" refers to a state of awareness describing a range of afflictions, associated with mental weakness. Such mental fatigue can manifest itself either as somnolence (decreased wakefulness) or as a general decrease of attention (not necessarily sleepiness). It may also be described as a decreased level of consciousness. Mental fatigue can be caused by continual mental effort and attention on a particular task, as well as high levels of stress or emotion. Basically, any mental process that goes into overload can result in mental fatigue.

[0027] As used herein, the term "headache" refers to a persistent or lasting pain or discomfort in the head region.

[0028] As used herein the term "attention" refers to the ability to direct and focus cognitive activity on specific stimuli. It is the ability or power to concentrate mentally.

[0029] As used herein, the term "decaffeinated coffee product" refers to a coffee product that has some, most or all of the caffeine removed (e.g., via a decaffeination process). For example, the coffee product can have a reduced amount of caffeine (e.g., 95% removal, 97% removal, 99% removal) compared to the amount normally associated with that coffee product.

[0030] As used herein a "non-coffee product" is a product which is not based on coffee or coffee extract as the main ingredient, but which may contain coffee components or extracts, e.g. chlorogenic acids, as a minor compound, or may contain a purified fraction of coffee, e.g. purified chlorogenic acids.

[0031] Chlorogenic acids have the general formula:

[0032] The most prevalent chlorogenic acids are given in the following table.

Name Stxuctxirc R3 R4 R5

Chlorogenic acids

5-O-caffeoyl-D-quinic acid C H II caffeoyl

(5CQA)

4-O-caffeoyl-D-quinic acid C H caffeoyl H

(4CQA)

C caffeoyl II H

(3CQA)

[0033] Other isomers exist which also fall within the definition of the structure given above. Therefore, in the context of the present disclosure, the phrase "chlorogenic acids" denotes all chlorogenic acid isomers, which are defined by the aforementioned structure.

[0034] In an embodiment, the present disclosure provides a method of improving alertness, improving attention, reducing tension, and/or reducing mental fatigue in an individual for at least 1 hour, preferably for at least 2 hours. The method comprises administering to an individual in need of improved alertness, improved attention, reduced tension, and/or reduced mental fatigue a decaffeinated coffee product to improve alertness, improve reaction attention, reduce tension, and/or reduce mental fatigue in the individual. The decaffeinated coffee product can be partially or fully decaffeinated. The decaffeinated coffee product can have a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

[0035] In another embodiment, the present disclosure provides a method of improving reaction time, reducing tiredness and/or reducing jitteriness in an individual, the method comprising: administering to an individual in need of improved reaction time, reduced tiredness and/or reduced jitteriness a decaffeinated coffee product to reduce tiredness, improve reaction time and/or reduce jitteriness in the individual, preferably for at least 1 hour, more preferably for at least 2 hours. The decaffeinated coffee product can be partially or fully decaffeinated. The decaffeinated coffee product can have a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

[0036] In an alternative embodiment, the present disclosure provides a method of reducing headache for at least 1 hour, preferably for at least 2 hours, in an individual, the method comprising: administering to an individual in need of reduced headache a decaffeinated coffee product to reduce headache in the individual. The decaffeinated coffee product can be partially or fully decaffeinated. The decaffeinated coffee product can have a similar effect in the individual as an approximately equivalent amount of a caffeinated coffee product.

[0037] The following discussion of the decaffeinated coffee products and extracts applies to any embodiments of the present disclosure. In an embodiment, the decaffeinated coffee product can include unroasted coffee, or roasted coffee, or a mixture of unroasted coffee and roasted coffee. In another embodiment, the decaffeinated coffee product can include a high content of chlorogenic acids or an amount of chlorogenic acids beyond the amount naturally associated with a roasted coffee product. In an alternative embodiment, the decaffeinated coffee product can include an amount of chlorogenic acids ranging from about 100 mg to about 10,000 mg per serving, including for example, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1 ,000 mg, 2,000 mg, 3,000 mg, 4,000 mg, 5,000 mg, 6,000 mg, 7,000 mg, 8,000 mg, 9,000 mg and the like and any amount therebetween. Preferably, the decaffeinated coffee product can include an amount of chlorogenic acids ranging from about 100 mg to about 5000 mg, such as from about 150 mg to about 1000 mg, per serving.

[0038] In another embodiment, the decaffeinated coffee is in the form of an extract. The extract can be derived from roasted coffee, unroasted coffee, (e.g., green coffee beans), or a mixture of unroasted coffee and roasted coffee (e.g., beans). Details of such an extract can be found, for example, in U.S. Patent Serial No. 11/911,046, which is incorporated herein by reference. In an embodiment, the extract can be derived from (i) a first portion including unroasted ground and/or unground coffee, in an amount of from 1 to 90% by weight based on the total weight of the coffee product, preferably in an amount of from 20% to 50%; and (ii) a second portion including ground coffee that has been roasted to a higher degree of roast than the first portion, in an amount of from 99 to 10% by weight based on the total weight of the coffee product, preferably from 80% to 50%. The content of the chlorogenic acids in the decaffeinated coffee product is preferably at least 4 g per 100 g of dry solids of the coffee product.

[0039] In any embodiments of the present disclosure, the extract can be derived from a mixture of green (e.g., unroasted) and roasted coffee beans in which the weight ratio of the green portion and roasted portion in the coffee product is from 1 :99 to 90: 10, alternatively from 20:80 to 50:50, alternatively from 30:70 to 45:55.

[0040] In an embodiment, the green coffee portion is substantially or wholly derived from Robusta coffee beans. In another embodiment, at least 65%, more preferably 75%, even more preferably 85%, most preferably 95%, for example 100% by weight of the green coffee beans are Robusta. This is because it has been found that Robusta coffee beans provide a greater level of chlorogenic acid per gram of bean than Arabica beans.

[0041] The roasted coffee portion may be a blend of Arabica and Robusta, although, in a preferred embodiment, the roasted portion is substantially or wholly derived from Arabica beans. This is because Arabica provides a richer taste and aroma profile, which is associated with coffee of higher quality.

[0042] The green coffee portion and/or the roasted coffee portion is partially or fully decaffeinated. However, it is particularly preferred that the green coffee portion is from fully decaffeinated coffee. Preferably the coffee product is used to provide a soluble coffee product.

[0043] The coffee beans to be extracted may be whole or ground. In an embodiment, green coffee beans are co-extracted with roasted coffee beans, i.e., green and roasted coffee beans are extracted simultaneously in the same extraction system to yield a mixed extract. The most volatile aroma components can be stripped from the beans before extraction, for example, if the extract is to be used for the production of pure soluble coffee. Methods for stripping of volatile aroma components are well known in the art, for example, from EP 1078576, which is incorporated herein by reference.

[0044] Following stripping, the less volatile components are then subjected to an "extraction" step. Extraction is a term common in the art of processing soluble coffee and indicate a process where water and/or steam are used to extract a complex mixture of coffee components from the roasted, ground coffee bean.

[0045] Extraction of coffee beans can be done using any suitable extraction method known to the skilled artisan. For example, extraction can be performed using water and/or steam as described in EP 0916267, which is incorporated herein by reference. In an embodiment, the coffee beans may be extracted by any suitable method yielding an extract including a desired amount of chlorogenic acids.

[0046] After extraction, the product may undergo a concentration step, following which, if a stripping step has taken place, the stripped aroma can be reintroduced into the resulting extract. Finally, the aromatized extract can be dried according to any standard procedure, such as freeze-drying, spray-drying or agglomerating. This produces a solid soluble product that may suitably be in the form of a powder or granules. If the extract has been dried, it may be resuspended as necessary for administration.

[0047] The soluble coffee mixture may be produced by co-extraction of the green portion and the roasted portion. Alternatively, the soluble coffee product can be produced by separately providing a roasted coffee portion and a green coffee portion and then extracting them individually before combining the resultant extracts. This is advantageous as the extraction conditions can be adapted to suit roasted and unroasted beans respectively.

[0048] The coffee extract may undergo any suitable treatment to remove undesired components of the extract. The extract may be separated from the extracted coffee beans by any suitable method, for example, filtration or centrifugation. The separation may be performed to the extent practically and economically feasible and needed in view of the desired use of the extract. The separation may thus not be 100% complete, for example, a minor part of undissolved material from the beans may still be present with the extract after separation.

[0049] In yet another embodiment, the present disclosure provides a method of improving alertness in an individual for at least 1 hour, the method comprising: administering to an individual in need of improved alertness a non-coffee product comprising a component selected from the group consisting of a decaffeinated coffee extract, chlorogenic acids and combinations thereof to improve attention in the individual.

[0050] In still another embodiment, the present disclosure provides a method of reducing jitteriness in an individual, the method comprising: administering to an individual in need of reduced jitteriness a non-coffee product comprising a component selected from the group consisting of a decaffeinated coffee extract, chlorogenic acids and combinations thereof to reduce jitteriness of the individual.

[0051] In still another embodiment, the present disclosure provides a method of reducing headache for at least 1 hour in an individual, the method comprising: administering to an individual in need of reduced headache a non-coffee product comprising a component selected from the group consisting of a decaffeinated coffee extract, chlorogenic acids and combinations thereof to improve the relaxation of the individual.

[0052] In any of the methods described herein, the chlorogenic acids can be derived, for example, from any suitable food source including coffee, tea, blackberry, potato or tomato. The chlorogenic acids can be derived, for example, from any suitable non-food source such as chemical synthesis. In an embodiment, the amount of chlorogenic acids added to the non-coffee product ranges from about 100 mg to about 10,000 mg per serving, including for example, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1 ,000 mg, 2,000 mg, 3,000 mg, 4,000 mg, 5,000 mg, 6,000 mg, 7,000 mg, 8,000 mg, 9,000 mg and the like and any amount therebetween. Preferably, the amount of chlorogenic acids added to the non-coffee product ranges from about 100 mg to about 5000 mg, such as from about 150 mg to about 1000 mg, per serving. The non-coffee product can be a food product, a beverage, a food supplement, a pet care product, a pharmaceutical product or a combination thereof.

[0053] In an alternative embodiment, the present disclosure provides a method of making a consumable product for improving an individual's mental capabilities. The method comprises providing a decaffeinated coffee extract for improving the individual's mental capabilities, and adding the decaffeinated coffee extract to a consumable product. The decaffeinated coffee extract may include an effective amount of chlorogenic acids for improving the individual's mental capabilities. The consumable product can be a food product, a beverage, a food supplement, a pet care product, a pharmaceutical product or a combination thereof. The mental capabilities can be alertness, mood, attention or a combination thereof.

[0054] In any embodiments of the present disclosure, the decaffeinated coffee extract can be used separately from the extracted coffee beans. The undissolved material from the beans can be substantially removed by separation as described herein and is not used in the production of the food or beverage product.

[0055] The decaffeinated coffee extract and/or chlorogenic acids can be added as an ingredient in any suitable form (e.g., liquid, powder, granules, etc.) to any suitable consumable product. In an embodiment, the consumable product may be any food or beverage product known in the art. For example, the food or beverage products can be a coffee beverage, pure soluble coffee, a soft drink, a dietary supplement, a dairy product, a cereal product, a fruit or vegetable juice product, or a confectionary product, such as a chocolate product, for example a chocolate drink. A soluble coffee product may be produced by concentrating and drying the decaffeinated coffee extract. A soluble coffee product produced from the decaffeinated coffee extract may be sold as such, or may, for example, be mixed with a creamer and/or sweetener and sold to prepare a coffee beverage including creamer and/or sweetener, for example, cappuccino or cafe latte.

[0056] In an embodiment, the present disclosure provides the use of a decaffeinated coffee extract to improve alertness, improve attention, reduce tension, and/or reduce mental fatigue in an individual for at least 1 hour, preferably for at least 2 hours. The decaffeinated coffee extract may comprise an extract of unroasted coffee. In another embodiment, the present disclosure provides the use of a decaffeinated coffee extract to reduce tiredness, improve reaction time and/or reduce jitteriness in an individual, preferably for at least 1 hour, more preferably for at least 2 hours. The decaffeinated coffee extract may be decaffeinated. [0057] In still another embodiment, the present disclosure provides the use of chlorogenic acids to reduce jitteriness in an individual, preferably for at least 1 hour, more preferably for at least 2 hours. In yet another embodiment, the present disclosure provides the use of chlorogenic acids to reduce headache of an individual for at least 1 hour, preferably for at least 2 hours. In yet another embodiment, the present disclosure provides the use of chlorogenic acids to reduce tiredness in an individual for at least 1 hour, preferably for at least 2 hours. The uses of chlorogenic acids disclosed herein may be performed e.g. by administrating chlorogenic acids to an individual for oral consumption, e.g. in the form of a coffee product, a decaffeinated coffee product as disclosed herein, or a non-coffee product as disclosed herein comprising chlorogenic acids. The use may be performed by administrating from about 100 mg to about 10,000 mg of chlorogenic acids to an individual for oral consumption, including for example, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1 ,000 mg, 2,000 mg, 3,000 mg, 4,000 mg, 5,000 mg, 6,000 mg, 7,000 mg, 8,000 mg, 9,000 mg and the like and any amount therebetween. Preferably, the amount of chlorogenic acids administered to an individual for oral consumption ranges from about 100 mg to about 5000 mg, such as from about 150 mg to about 1000 mg.

[0058] In another embodiment, the present disclosure provides a method of increasing sports performance in an individual for at least 1 hour, preferably for at least 2 hours. The method comprises administering to an individual in need thereof a decaffeinated coffee product comprising an unroasted coffee to increase the sports performance in the individual. In an alternative embodiment, the present disclosure provides a method of increasing sports performance in an individual for at least 1 hour, preferably for at least 2 hours. The method comprises administering to an individual in need of thereof a non-coffee product comprising a component selected from the group consisting of a decaffeinated coffee extract, chlorogenic acids and combinations thereof to increase the sports performance in the individual.

[0059] Caffeine is known to improve sports performance by improving attention, increasing alertness, and reducing mental fatigue (thus the improvement comes directly from improving cognitive function). Accordingly, improvements in cognitive processes as discussed herein are the same attributes that have been known to improve sports performance (e.g., alertness, sustained attention, reducing mental fatigue). EXAMPLES

[0060] By way of example and not limitation, the following examples are illustrative of various embodiments of the present disclosure.

EXAMPLE 1

[0061] Cognitive and mood data were collected from 66 healthy older participants (50+) who were light to moderate coffee drinkers (i.e. drinking no more than 8 cups of coffee per week). A randomised, double blind, placebo-controlled cross-over-design was employed. Each participant was tested under three acute oral coffee conditions: 1) 540 mg chlorogenic acid (equivalent to level found in 3 servings of decaffeinated Green Blend) mixed in a placebo matrix (5460mg maltodextrin and CHE mixed with coffee flavour and colour; 6g), 2) decaffeinated Green Blend coffee (6g), and 3) placebo (6g; maltodextrin and CHE mixed with coffee flavour and colour). A selected battery of cognitive tasks were performed to measure attention, emotional attention, information processing speed, reaction time performance, and mood.

Objectives

[0062] The primary objective was to evaluate whether an acute dose of chlorogenic acid (CGA) improves cognitive function and mood in healthy older adults.

[0063] The secondary objectives were to:

[0064] 1.) Evaluate whether it is the CGAs found in decaffeinated coffee that are attributed to the cognitive and mood enhancing effects;

[0065] 2.) Replicate the positive acute effects of 6 grams Green Blend decaffeinated coffee on attention and mood;

Description of tests

[0066] N-back task is a measure of sustained and selective attention and impulsivity. Single digits are presented on the screen. Participants are required to press 'YES' or 'NO' using a button box, to indicate whether the digit is the same as the n previously (e.g. 1-back the previous digit, 3-back the digit 3 previously). The task is scored for speed and accuracy. The duration of the task is approximately 4 minutes.

[0067] Jensen's Box Reaction Time task is an apparatus that distinguishes decision time and movement time from total reaction time. This apparatus has eight lights which are arranged in a semi-circular configuration. A response button is located adjacent to each light. A "home" button is situated in the centre of the panel. Subjects are required to press the home button until they see a target light and then to release the home button as quickly as possible and to press the response button adjacent to the stimulus light. Decision time (DT) is defined as the time from stimulus onset to the release of the home button, and movement time (MT) as the time from release of the home button to the depression of the stimulus button. Choice is manipulated by varying the number of stimulus alternatives, from 0 (i.e. one light at one possible location) to multiple (i.e. the stimulus may appear in any one of the eight light positions). Participants will be given several practice trials in the eight stimulus (i.e. eight lights) condition so that they can familiarise themselves with the task. DTs of less than 150 ms are discarded as outliers, as it has been argued that physiological limits prevent shorter DTs (Jensen, 1987). DTs over 999 ms will also be discarded and replaced with an additional trial. In addition, all DTs exceeding three SDs above the subject's mean DT are also discarded (Jensen, 1987). The outcome measures are the median, mean and intra- individual variability (*i - average standard deviation) of both DT and MT for all choice, intercept of the DT function across choice and the slope of this function.

[0068] Bond and Lader Visual Analogue Scales (VAS) (Bond & Lader, 1974) is a frequently used self-evaluation mood and alertness rating scale. In total, 16 dimensions of mood are given. The participant is required to mark, on a 100 mm line to what extent the described state is appropriate to him/her at that moment in time. The Bond and Lader VAS discriminates three affective dimensions: alertness, contentment, and calmness.

[0069] Caffeine Research Visual Analogue Scales consists of seven visual analogue scales ("relaxed", "alert", "jittery", "tired", "tense", "headache", overall mood") that have previously been used in research into the effects of caffeine (Rogers et al, 2003). In addition, a single "mentally fatigued" visual analogue scale was included, as previous research has shown it to be sensitive to a caffeine-glucose drink (Kennedy & Scholey, 2004).

[0070] Cognitive performance and mood was assessed at baseline, 40 minutes and 120 minutes post treatment consumption.

Design

[0071] This was an acute cross-over, placebo-controlled, double blind, randomized, single centre, clinical trial with three treatment conditions: chlorogenic acid, Green Blend decaffeinated coffee and placebo. Subjects

[0072] Sixty healthy older adults completed the study. Criteria for inclusion was: healthy older adults (male and female) aged 50+; light to moderate coffee drinkers (i.e. with caffeine), where subjects drink no more than 8 cups of coffee a week; no existing or preexisting physical or neurological conditions, no history of psychiatric, cardiac, endocrine, gastrointestinal, or bleeding disorders, not taking any medication that could potentially affect the outcome of the study (i.e. psychoactive medication) including drugs, excessive amounts of alcohol, non-smokers, not on a potassium reduced diet, not under treatment with spironolactone-like anti-diuretics, aldosteron-receptors antagonists or angiotensin II- antagonists and no food allergies.

Products tested

[0073] Chlorogenic acid in placebo matrix (maltodextrin and CHE mixed with coffee flavour and colour); Green Blend decaffeinated coffee; and placebo (maltodextrin and CHE mixed with coffee flavour and colour).

[0074] Amount, dosage, route of administration, duration of treatment:

540 mg chlorogenic acid mixed in a placebo matrix (5460mg maltodextrin and

CHE mixed with coffee flavour and colour) ("CGA"). The CGA is equivalent to the level found in 3 servings of a Green Blend decaffeinated coffee

Green Blend Decaffeinated coffee ("Green" or "Green Blend Decaf): A decaffeinated soluble coffee product produced by co-extraction of a blend of 65% by weight of roasted coffee beans and 35% by weight of unroasted coffee beans

(6g);

Placebo (6 g maltodextrin and CHE based with coffee flavour, colour and aroma). The composition of each coffee treatment are summarized in Table 1.

Table 1

Samples Unit Green Blend Decaf Placebo CGA

Caffeine g/lOOg as such 0.08 0.01 0.16

Chlorogenic acids g/lOOg as such 8.86 0.00 9.30

3CQA g/lOOg as such 2.01 0.00 1.52

4CQA g/lOOg as such 2.35 0.00 2.43

5CQA g/lOOg as such 2.58 0.00 2.56

3,4diCQA g/lOOg as such 0.32 0.00 0.60 3,5diCQA g/lOOg as such 0.18 0.00 0.36

4,5diCQA g/lOOg as such 0.28 0.00 0.55

4FQA g/lOOg as such 0.42 0.00 0.54

5FQA g/lOOg as such 0.72 0.00 0.74 caffeic acid g/lOOg as such 0.01 0.00 0.09

Per servings Unit Green Blend Decaf Placebo CGA dosage g /cup 6.00 6.00 5.70

Caffeine mg/cup 5.0 0.7 8.8

Chlorogenic acids mg/cup 532 0 530

[0075] All treatments were administered orally as a hot coffee beverage which was drunk within 15 minutes. Participants consumed each of the coffee beverages on separate testing days. Experimental testing sessions were separated by at least a one week washout period.

Statistical analysis

[0076] All dependent variables were tested for normality using the Box-Cox Log- likelihood plots for various values of lambda. In cases where the 95% confidence interval covered lamda = 1 the data was left as is. In cases where the confidence interval did not cover 1 the data was transformed using the appropriate box-cox power transformation. In many cases the logarithm or square root was appropriate for normalizing the data, while in isolated cases inverse or squared transformations were also used. The normality of the transformed data was subsequently confirmed using Kolmogorov-Smirnov.

[0077] All analysis of variance was conducted using SAS 9.2 with repeated measures mixed

[0078] modelling (PROC MIXED). The multivariate correlated error approach was used, whereby within- subject parameter estimates of residual covariance were estimated for each combination of time and treatment. This model was compared with a secondary model whereby each participant was treated as a random effect, and the former correlated error approach was found to result in superior fit (lower AIC value). The Residual Maximum Likelihood estimation method (REML) was used with unstructured (UN) covariance and a between-within degrees of freedom method. Fixed terms were fitted for the Treatment Effect (Placebo, Green Blend, CGA) and Time since dosing (40 mins, 120 mins). Baseline performance was fitted as a covariate and the interaction of Treatment* Visit was specified as the Repeated term.

[0079] Post-hoc differences of least squares means were compared between all levels of treatment and time. Significance values were reported using both unadjusted p-values as well as with Hommel correction of p-values for multiple comparisons. An alpha level of 0.05 was set for statistical significance of least square differences, when using the Hommel corrected p-values (highlighted in colour in tables of results). However, to allow greater exploration of the data, any least square differences associated with uncorrected p-values <.100 were taken as trend level and have also been discussed in text (highlighted in grey in tables of results).

RESULTS

N-Back task

Analysis Variable : NBack Correct Reaction Time (ms)

Lower 95% Upper 95%

Treatment Time Obs Mean Median N Std Dev Std Error CL for Mean CL for Mean Minimum Maximum

Placebo Pre 60 1142 101960 409.3 52.84 1036 1248 637.1 2559

40 60 1137 103060 445.8 57.55 1021 1252 466.3 2459

120 60 1086 966.760 406.5 52.48 981.4 1191 601.4 2749

Green Pre 60 1131 1043 60 418.1 53.98 1023 1239 598.4 2418

40 60 1041 960.760 363.5 46.93 947.3 1135 373.4 2370

120 60 1013 920.1 60 366.8 47.35 918.6 1108 294.7 2702

CGA Pre 60 1125 106560 408.6 52.75 1020 1231 596.0 2431

40 60 1076 968.960 452.6 58.43 958.7 1193 488.6 3190

120 60 1048 952.660 354.6 45.78 956.4 1140 541.7 2304

[0080] Mixed ANCOVA adjusting for baseline accuracy and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was near-significant (F-value=3.12, p-value=0.05), while the Treatment* Time interaction was non- significant (F-value=0.46, p-value=0.63).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treat im-iif 2 59 3.12 0.0516

Time 1 59 3.56 0.0641

Treatment*Time 2 59 0.46 0.6321 tNBack CorrectRT Baseline 1 59 206.80 <.0001 [0081] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper I o C^n η,κ,, Ρ .U. S, , 2.45 „„n., ,,„s ,,.,, , Ι * -. . 14s

Placebo CGA 0.03270 0.02784 1.17 0.2449 0.24 -0.02300 0.08840

Green CGA -0.03047 0.02297 -1.33 0.1898 0.24 -0.07644 0.01549

Placebo 40 Placebo 120 0.04015 0.02676 1.50 0.1389 0.28 -0.01340 0.09371

Placebo 40 Green 40 0.06775 0.03161 2.14 0.0363 0.1 1 0.004487 0.13 10

Placebo 40 CGA 40 0.04855 0.03566 1.36 0.1785 0.36 -0.02280 0.1199

Placebo 120 Green 120 0.05860 0.02983 1 .96 , 0.0542 0. 16 -0.00108 0. 1 1 X3

Placebo 120 CGA 120 0.01685 0.02990 0.56 0.5753 0.58 -0.04298 0.07668

Green 40 Green 120 0.03101 0.01813 1.71 0.0925 0.21 -0.00528 <).<)(Γ3( Ι

Green 40 CGA 40 -0.01919 0.02629 -0.73 0.4682 0.47 -0.07179 0.03341

Green 120 CGA 120 -0.04175 0.02898 -1.44 0.1549 0.31 -0.09973 0.01623

CGA 40 CGA 120 0.008450 0.02545 0.33 0.7410 0.74 -0.04247 0.05937

[0082] At both 40 minutes and 120 minutes post-treatment, there was a trend towards reaction time (RT) being faster in the Green Blend group in comparison to placebo (p-values = 0.1 1 and 0.21 respectively). There was also a trend towards a reduction in RT from 40 to 120 minutes in the Green Blend group (p-value=0.21). Overall, RT was found to be significantly faster after consuming Green Blend in comparison to Placebo (p-value=0.05).

Jenson Box task

Analysis Variable(s) : Jensen Decision Time (ms)

Lower Upper

95% 95%

Std CL for CL for

Treat Time Obs Mean Median N Dev Std Error Mean Mean Minimum Maximum

2-ch Placebo Pre 60 342.9 338.5 60 58.00 7.488 327.9 357.8 231.0 504.0

40 60 354.9 350.0 60 54.17 6.993 340.9 368.9 218.0 489.0

120 60 351.3 344.0 60 58.14 7.506 336.3 366.4 234.0 554.0

Green Pre 60 354.2 340.5 60 64.55 8.334 337.5 370.8 249.0 522.0

40 60 350.7 340.0 60 59.66 7.703 335.3 366.1 260.0 475.0

120 60 356.9 347.5 60 58.31 7.527 341.9 372.0 250.0 516.0

CGA Pre 60 344.4 337.5 60 52.98 6.840 330.7 358.1 221.0 461.0

40 60 353.6 341.5 60 62.51 8.069 337.4 369.7 220.0 519.0

120 60 357.5 349.5 60 53.83 6.950 343.6 371.4 256.0 490.0

4-ch Placebo Pre 60 363.5 351.5 60 60.13 7.762 348.0 379.0 225.0 588.0

40 60 369.4 358.0 60 59.37 7.665 354.1 384.7 236.0 548.0

120 60 372.1 359.0 60 64.04 8.268 355.5 388.6 260.0 600.0

Green Pre 60 368.9 351.0 60 62.26 8.038 352.8 385.0 267.0 532.0

40 60 365.4 361.5 60 56.95 7.353 350.6 380.1 253.0 500.0

120 60 370.4 364.5 60 54.98 7.097 356.2 384.6 260.0 506.0

CGA Pre 60 362.2 353.5 60 55.32 7.142 347.9 376.5 244.0 492.0 Analysis Variable(s) : Jensen Decision Time (ms)

Lower Upper

95% 95%

Std CL for CL for

Treat Time Obs Mean Median N Dev Std Error Mean Mean Minimum Maximum

40 60 370.0 357.0 60 54.94 7.092 355.8 384.2 234.0 497.0 120 60 373.9 370.0 60 55.82 7.206 359.5 388.3 255.0 508.0

[0083] Jenson 2-choice. Mixed ANCOVA adjusting for baseline accuracy and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was non-significant (F-value=1.87, p-value=0.16) while the Treatment* Time interaction was approaching significance (F-value=2.36, p-value=0.10).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 1.87 0.1637

Time 1 59 1.50 0.2251

Trealmeiil ' -Tinie 2 59 2.36 0.1034 tJensen2 DT Baseline 59 262.24 <.0001

[0084] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 0.02039 0.01267 1.61 0.1129 0.23 -0.00496 0.04575 Placebo CGA -0.00132 0.01222 -0.11 0.9145 0.91 -0.02577 0.02314 Green CGA -0.02171 0.01238 - 1 .75 11.DS4 0.17 -0.04648 0.003057

Placebo 40 Placebo 120 0.01 133 0.01041 1.09 0.2807 0.28 -0.00950 0.03216

Placebo 40 CGA 40 0.01191 0.01593 0.75 0.4576 0.46 -0.01997 0.04379

Placebo 120 Green 120 0.005318 0.01478 0.36 0.7203 0.72 -0.02426 0.03490

Placebo 120 CGA 120 -0.01455 0.01300 -1.12 0.2678 0.54 -0.04057 0.01147

(ireen 40 Green 120 -0.01882 t l.O K M Ki -1.87 ( ) .2 ( ) -o. ( i S44 0.001303

Green 40 CGA 40 -0.02356 0.01569 -1.50 0.1386 0.28 -0.05496 0.007838

Green 120 CGA 120 -0.01987 0.01289 -1.54 0.1287 0.39 -0.04567 0.005935

CGA 40 CGA 120 -0.01512 0.01132 -1.34 0.1868 0.28 -0.03778 0.007533

[0085] At 40 minutes post-treatment, subjects receiving Green Blend displayed significantly faster decision time (DT) in comparison to the placebo group (p-value = 0.05). There was also a trend towards DT being faster in the Green Blend group in comparison to CGA overall (p-value=0.17). From 40 to 120 minutes post treatment there was a trend towards an increase in DT in the Green Blend group (p=0.20). [0086] Jenson 4-choice. Mixed A COVA adjusting for baseline accuracy and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was approaching significance (F-value=2.58, p-value=0.08) while the Treatment* Time interaction was non- significant (F-value=0.16, p-value=0.85).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 2.58 0.0845

Time 59 3.62 0.0619

Treatment*Time 2 59 0.16 0.8536

tJensen4 DT Baseline 1 59 398.12 <.0001

[0087] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted

(using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 0.01666 0.01131 1.47 0.1462 0.29 -0.00598 0.03930

Placebo CGA -0.00702 0.01145 -0.61 0.5422 0.54 -0.02993 0.01589

Green CGA -0.02368 0.01071 -2.21 0.0309 0.09 -0.04510 -0.00226

Placebo 40 Placebo 120 -0.00562 0.01208 -0.47 0.6434 0.64 -0.02980 0.01856

Placebo 40 Green 40 0.02124 0.01474 1.44 0.1547 0.31 -0.00824 0.05073

Placebo 40 CGA 40 -0.00466 0.01403 -0.33 0.7410 0.74 -0.03272 0.02341

Placebo 120 Green 120 0.01208 0.01309 0.92 0.3601 0.48 -0.01412 0.03828

Placebo 120 CGA 120 -0.00938 0.01333 -0.70 0.4844 0.48 -0.03606 0.01730

Green 40 Green 120 -0.01478 0.009874 -1.50 0.1397 0.34 -0.03454 0.004974

Green 40 CGA 40 -0.02590 0.01221 -2. 12 0.0381 0. 1 1 -i ) . ( ) 5033 -0.00147 :

Green 120 CGA 120 -0.02146 0.01335 -1.61 0.1133 0.34 -0.04817 0.005253

CGA 40 CGA 120 -0.01035 0.008492 -1.22 0.2280 0.46 -0.02734 0.006648

[0088] At 40 minutes post-treatment there was a trend towards subjects receiving CGA to display slower Decision Time (DT) in comparison to those receiving Green Blend (p-value=0.11).

Movement Time

[0089] Outlier Removal: Participant Number 8 in the Green Blend condition at 120 minutes was removed due to a 1 millisecond movement time. This movement time is not physiologically feasible, and is due to either anticipatory response or data entry error. Analysis Variable(s) : Jensen Decision Time (ms)

Lower Upper

95% 95%

Std CL for CL for

Treat Time Obs Mean Median N Dev Std Error Mean Mean Minimum Maximum

4-ch Placebo Pre 60 671.0 661.5 60 114.9 14.83 641.3 700.7 386.0 968.0

40 60 678.2 675.0 60 109.7 14.16 649.9 706.5 402.0 956.0

120 60 684.6 682.0 60 116.3 15.01 654.6 714.7 420.0 1013.0

Green Pre 60 678.3 653.0 60 113.0 14.59 649.1 707.5 476.0 915.0

40 60 678.3 666.5 60 111.8 14.44 649.4 707.2 475.0 944.0

120 60 683.7 663.0 60 112.7 14.55 654.5 712.8 464.0 946.0

CGA Pre 60 665.7 652.5 60 109.8 14.18 637.3 694.0 422.0 991.0

40 60 678.9 679.5 60 108.1 13.96 651.0 706.9 388.0 909.0

120 60 689.8 676.5 60 114.1 14.73 660.3 719.3 468.0 972.0

[0090] Jensen 4-choice. Mixed A COVA adjusting for baseline movement time and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was approaching significance (F-value=2.58, p-value=0.08) while the Treatment* Time interaction was non- significant (F-value=0.25, p-value=0.78).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment . . . 2 ^ 59 2.58 0.0845

Time 59 5.73 0.0199

Treatment*Time 2 59 0.25 0.7806 baseline 1 59 711.55 <.0001

[0091] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj p Lower Upper

Placebo Green 0.01040 0.009340 1.11 0.2702 0.29 -0.00829 0.02908

Placebo CGA -0.01054 0.009854 -1.07 0.2890 0.29 -0.03026 0.009175

Green CGA -0.02094 0.009239 -2.27 0.0271 0.08 -0.03943 -<i.oi ) 245

Placebo 40 Placebo 120 -0.00808 0.007901 -1.02 0.3106 0.43 -0.02389 0.007729

Placebo 40 Green 40 0.01023 0.01199 0.85 0.3972 0.56 -0.01377 0.03422

Placebo 40 CGA 40 -0.00698 0.01186 -0.59 0.5584 0.56 -0.03072 0.01676

Placebo 120 Green 120 0.01056 0.01113 0.95 0.3465 0.35 -0.01171 0.03284

Placebo 120 CGA 120 -0.01410 0.01051 -1.34 0.1847 0.35 -0.03513 0.006922

Green 40 Green 120 -0.00774 0.009832 -0.79 0.4341 0.43 -0.02742 0.01193

Green 40 CGA 40 -0.01721 0.01068 -1.61 0.1125 0.34 -0.03858 0.004162

Green 120 CGA 120 -0.02467 0.01283 -1.92 0.0593 0.18 -0.05034 0.00 1 003

CGA 40 CGA 120 -0.01520 0.008307 -1.83 0.0723 0.22 -0.03182 0.001418

[0092] At 120 minutes post-treatment, there was a trend towards subjects consuming Green Blend displaying faster MT in comparison to CGA (p-value=0.18). Overall, there was also a trend towards subjects in the Green Blend group displaying faster MT in comparison to the CGA group (p-value=0.08).

Bond & Lader Visual Analogue Scales

[0093] Outlier Removal: Due to the fact that possible scores are limited between 0 and 100 on all Bond-Lader scales, no outliers were removed from the dataset. However, a number of transformations were required in order to normalize the data.

Alertness

Analysis Variable : Bond-Lader ScoreAlert2

Lower 95% Upper 95%

Std Std CL for CL for

Treat Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 64.06 60.50 60 19.18 2.476 59.11 69.02 27.38 99.67

40min 60 59.90 57.45 60 21.31 2.751 54.40 65.41 13.11 99.67

120min 60 56.76 55.56 60 20.48 2.644 51.47 62.05 11.89 99.89

Green Blend Pre 60 63.48 67.00 60 19.59 2.529 58.42 68.54 19.67 100.0

40min 60 61.49 60.78 60 20.12 2.598 56.29 66.69 13.33 100.0

120min 60 59.51 57.00 60 21.05 2.718 54.07 64.94 14.78 99.56

CGA Pre 60 66.29 68.11 60 18.17 2.346 61.59 70.98 33.67 100.0

40min 60 59.95 58.78 60 20.05 2.589 54.77 65.13 14.67 99.56

120min 60 57.09 60.72 60 20.24 2.613 51.86 62.31 15.33 99.67

[0094] Mixed ANCOVA adjusting for baseline accuracy and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be significant (F-value=4.18, p-value=0.02), while the

Treatment* Time interaction was found to be non-significant (F-value=0.36, p-value=0.70).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Si) U K

■■llilM 4. 1 s 0 < P( I( I

Time 1 59 10.44 " o ' .oo o

Treatment*Time 2 59 0.36 0.6960 baseline 1 59 442.14 <.0001

[0095] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green -2.6912 1.5153 78 0.0809 0Λ6 -5.7233 0.3409

Placebo CGA 1.8075 1.3347 1.35 0.1808 0.18 -0.8632 4.4782

Placebo 1.0960 4.9822 Placebo -6.2947 -0.2451 Placebo -1.2986 4.6425 Green -0.2049 4.1712 Given 0.6907 7.4203

lil l 4,»,, .J* n.,.,,5, ,,„: u ™ ■■■iii

CGA 40 CGA 2.8695 1.3424 2.14 0.0367 0.07 0.1835 5.5555

[0096] B-L Alertness was found to be significantly higher in the Green Blend group in comparison to CGA at 120 minutes (p-value=0.02). Similarly, there was a trend towards B-L Alertness being higher in the Green Blend group in comparison to placebo at 120 minutes (p-value=0.07). At 40 minutes post-treatment there was a trend towards Alertness being higher in the Green Blend group in comparison to placebo (p-value=0.06). In the placebo group Alertness significantly decreased from 40 to 120 minutes post-treatment (p- value = 0.008). Overall, B-L Alertness was found to be significantly higher after receiving Green Blend in comparison to CGA (p-value=0.02).

Caffeine Research Visual Analogue Mood Scales (Caff- VAS)

[0097] Outlier Removal: As with the Bond-Lader scales, possible scores for the Caff- VAS scales are limited between 0 and 100, and for this reason no outliers were removed from the Caffeine VAS dataset. However, a number of transformations were required in order to normalize the data.

Alert

Analysis Variable : CaffVAS Alert2

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 62.67 59.50 60 21.39 2.761 57.14 68.19 17.00 100.0

40min 60 57.12 55.00 60 21.27 2.745 51.62 62.61 9.000 100.0

120min 60 51.40 48.50 60 21.99 2.839 45.72 57.08 4.000 100.0

Green Blend Pre 60 60.20 62.50 60 22.81 2.945 54.31 66.09 19.00 100.0

40min 60 58.42 57.00 59 22.66 2.950 52.52 64.33 13.00 98.00

120min 60 56.65 53.50 60 21.77 2.810 51.03 62.27 10.00 100.0

CGA Pre 60 61.95 63.50 60 21.52 2.778 56.39 67.51 9.000 99.00

40min 60 55.95 56.00 60 24.05 3.105 49.74 62.16 3.000 100.0 Analysis Variable : CaffVAS Alert2

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

120min 60 49.43 46.00 60 21.65 2.795 43.84 55.03 5.000 99.00

[0098] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be significant (F-value=3.40, p-value=0.04) while the Treatment*Time interaction was found to be non-significant (F-value=2.06, p-value=0.14).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

1 1 mi liu m Ι tiίiΐiίiίwΐίlΐlϊi Ι tiίiΐiiίwιίlΐlϊi tiiiiw tilHiiw tilHiiw 3.4.. .....4«.

Time 1 59 17.97 <.0001

Treatment*Time 2 59 2.06 0.1365 baseline 1 59 147.90 <.0001

[0099] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment*Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Placebo 40 Green 40 -2.9439 2.4649 -1.19 0.2371 0.47 -7.8762 1.9884

Placebo 40 CGA 40 0.7059 2.8132 0.25 0.8027 0.80 -4.9233 6.3350

1 20

Placebo 120 CGA 120 1.5059 2.2648 0.66 0.5087 0.51 -3.0259 6.0377" "* '

Green 40 Green 120 1.8246 1.3125 1.39 0.1697 0.17 -0.8017 4.4509

Green 40 CGA 40 3.6498 3.0032 1.22 0.2291 0.46 -2.3597 9.6592

[00100] 120 minutes after receiving treatments, subjects receiving Green Blend were found to be significantly more Alert than those receiving both placebo (p-value=0.02) and CGA (p-value=0.009). This can be attributed to significant decreases in Alertness from 40 to 120 minutes in both the Placebo group (p-value=0.001 ) and the CGA group (p- value=0.03). Overall, subjects were found to be significantly more Alert post-treatment after receiving Green Blend in comparison to CGA (p-value=0.05). A similar trend was also observed for Green Blend in comparison to Placebo (p-value=0.06). Jittery

Pre-Testing

Analysis Variable : CaffVAS Jitteryl

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 14.45 11.50 60 12.16 1.570 11.31 17.59 0 55.00

40min 60 18.97 13.00 60 17.36 2.242 14.48 23.45 0 81.00

120min 60 17.70 13.00 60 16.59 2.142 13.41 21.99 0 63.00

Green Blend Pre 60 18.97 15.00 60 16.89 2.180 14.60 23.33 0 77.00

40min 60 16.32 12.50 60 13.85 1.789 12.74 19.90 0 57.00

120min 60 17.10 10.00 60 15.93 2.057 12.98 21.22 0 65.00

CGA Pre 60 18.73 12.50 60 17.49 2.258 14.22 23.25 0 86.00

40min 60 16.35 10.00 60 15.03 1.940 12.47 20.23 0 58.00

120min 60 18.10 14.50 60 16.38 2.115 13.87 22.33 0 61.00

[00101] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was approaching significance (F-value=2.46, p-value=0.09), while the Treatment* Time interaction was non-significant (F-value=1.43, p-value=0.25).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 2.46 0.0938

Time 1 59 0.00 0.9875

Treatment*Time 2 59 1.43 0.2485 baseline 1 59 78.12 <.0001

[00102] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 0.3458 2. 1 - 0.0354 0.11 0.02445 0.6671

Placebo CGA 0.3001 0.1714 1.75 0.0851 0.17 -0.04278 0.6430

Green CGA -0.04566 0.1458 -0.31 0.7552 0.76 -0.3373 0.2460

Placebo 40 Placebo 120 0.1312 0.1964 0.67 0.5069 0.99 -0.2619 0.5242

Placebo 40 Green 40 i 0.4123 0.1842 2.24 0.0290 0.06 0.04378 0.7808

Placebo 40 CX A. 40 0.4278 J 0.1942 \ 2.20 0.0315 0.06 0.03928 0.8163

Placebo 120 Green 120 0.2793 0.2101 1.33 0.1888 0.53 -0.1411 0.6996

Placebo 120 CGA 120 0.1724 0.1845 0.93 0.3537 0.55 -0.1967 0.5415

Green 40 Green 120 -0.00184 0.1180 -0.02 0.9876 0.99 -0.2380 0.2343

Green 40 CGA 40 0.01553 0.1625 0.10 0.9242 0.92 -0.3096 0.3406

Green 120 CGA 120 -0.1068 0.1777 -0.60 0.5499 0.55 -0.4624 0.2487

CGA 40 CGA 120 -0.1242 0.1390 -0.89 0.3751 0.76 -0.4023 0.1539 [00103] At 40 minutes post-treatment there was a trend towards subjects receiving Green Blend being significantly less jittery than those in the placebo group (p- value=0.06). A similar trend was also observed for the CGA group in comparison to placebo at 40 minutes (p-value=0.06). Overall, CaffVAS- Jittery was found to be lower in the Green Blend treatment in comparison to placebo (p-value=0.1 1) as well as in the CGA group in comparison to placebo (p-value=0.17).

Tired

Pre-Testing

Analysis Variable : CaffVAS Tiredl

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 26.50 25.00 60 17.62 2.274 21.95 31.05 0 71.00

40min 60 34.03 28.50 60 21.99 2.839 28.35 39.71 0 81.00

120min 60 40.45 39.00 60 20.27 2.616 35.21 45.69 0 76.00

Green Blend Pre 60 26.75 24.00 60 20.10 2.595 21.56 31.94 0 83.00

40min 60 32.92 30.50 60 20.99 2.709 27.50 38.34 0 73.00

120min 60 36.25 34.00 60 20.67 2.668 30.91 41.59 1.00 82.00

CGA Pre 60 29.62 23.00 60 22.72 2.933 23.75 35.48 0 84.00

40min 60 33.33 29.00 60 21.18 2.735 27.86 38.81 0 99.00

120min 60 36.97 36.00 60 20.82 2.688 31.59 42.35 1.00 82.00

[00104] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be non-significant (F-value=.17, p-value=0.32) as well as the

Treatment* Time interaction (F-value=0.99, p-value=0.38).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 1.17 0.3173

Time 1 59 9.92 0.0026

Treatment*Time 2 59 0.99 0.3762 baseline 1 59 55.76 <.0001

[00105] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted

(using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 0.4034 0.2995 1.35 0.1832 0.37 -0.1959 1.0028

Placebo CGA 0.4579 0.3687 1.24 0.2191 0.44 -0.2798 1.1956

Green CGA 0.05452 0.3591 0.15 0.8799 0.88 -0.6641 0.7731

■ 4.. Pkuvho 1 2» - 1 .23 , 2 45 -:„2 , s „.,,„ -2,.:o, -„ Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo 40 Green 40 0.1157 0.3681 0.31 0.7544 0.89 -0.6209 0.8523

Placebo 40 CGA 40 0.1888 0.5377 0.35 0.7268 0.89 -0.8872 1.2647

Placebo 120 Green 120 0.6911 0.3886 1.78 ii.osm 0.16 -0.08634 1.4686

Placebo 120 CGA 120 0.7271 0.3718 1.96 0.0553 0.12 -0.01690 1.4711

Green 40 Green 120 -0.6557 j 0.3795 -1.73 0.0892 0.15 ' -1.4151 0.1036

Green 40 CGA 40 0.07310 0.5214 0.14 0.8890 0.89 -0.9701 1.1163

Green 120 CGA 120 0.03594 0.4261 0.08 0.9331 0.93 -0.8167 0.8886

CGA 40 CGA 120 -0.6929 0.4790 -1.45 0.1533 0.15 -1.6513 0.2655

[00106] There was a significant increase in Tiredness observed in the Placebo group from 40 to 120 minutes (p-value=0.008). At 120-minutes post-treatment there was a trend towards Tiredness being higher in the placebo in comparison to Green Blend (p- value=0.16) as well as CGA (p-value=0.12).

Post-testing

Analysis Variable : CaffVAS Tired2

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 38.38 41.50 60 22.42 2.894 32.59 44.17 0 94.00

40min 60 47.13 49.00 60 23.40 3.021 41.09 53.18 0 90.00

120min 60 49.95 53.00 60 21.94 2.832 44.28 55.62 1.000 91.00

Green Blend Pre 60 35.98 36.50 60 21.73 2.805 30.37 41.60 0 81.00

40min 60 44.39 45.00 59 24.81 3.230 37.92 50.86 1.000 93.00

120min 60 46.63 47.00 60 23.27 3.004 40.62 52.64 0 92.00

CGA Pre 60 34.95 32.00 60 21.84 2.819 29.31 40.59 0 83.00

40min 60 39.80 40.50 60 21.35 2.756 34.28 45.32 0 87.00

120min 60 50.45 51.50 60 21.76 2.809 44.83 56.07 2.000 89.00

[00107] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be non-significant (F-value=0.50, p-value=0.61) whilst the

Treatment* Time interaction was found to be significant (F-value=3.79, p-value=0.03).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 0.50 0.6066

Time 1 59 15.06 0.0003

I reahm m l ime ^^^^^^^^^^ MfMNMIifM I ) ( N^ baseline 1 59 70.18 'Α'Λ <.οοοϊ '

[00108] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported. Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 1.9456 2.5790 0.75 0.4536 0.91 -3.2150 7.1062

Placebo CGA 1.9361 2.1779 0.89 0.3776 0.76 -2.4219 6.2940

Green CGA -0.00955 2.7149 -0.00 0.9972 0.997 -5.4421 5.4230

Placebo 40 Placebo 120 -2.8167 2.1813 -1.29 0.2016 0.40 -7.1814 1.5480

Placebo 40 Green 40 1.6096 3.6123 0.45 0.6575 0.66 -5.6187 8.8378

Placebo 4.. C GA 4.. 5.X52 " 2.3 1 5* 2.53 .....142 .....4 1 . 1 W K Sf

Placebo 120 Green 120 2.2817 3.2652 0.70 0.4874 0.51 -4.2519 8.8153

Placebo 120 CGA 120 -1.9806 2.9556 -0.67 0.5054 0.51 -7.8948 3.9336

Green 40 Green 120 -2.1445 3.5547 -0.60 0.5486 0.55 -9.2575 4.9684

Green 40 CGA 40 4.2432 3.7863 1.12 0.2670 0.53 -3.3332 11.8196

Green 120 CGA 120 -4.2623 3.3566 -1.27 0.2091 0.51 -10.9788 2.4543

Π .Λ 4.. Π .Λ 1 2.. - I <>. ( ,5...> 2.2'>24 -4.( . .IK... I - 1 5.23- j -<M

[00109] At 40 minutes post-treatment, subjects in the CGA group were found to be significantly less tired than those receiving placebo (p-value=0.04). However, a significant increase in Tiredness was also observed in the CGA group from 40 to 120 minutes post-treatment (p-value<.0001) whilst levels remained relatively unchanged in the placebo group over this time period.

Tense

Pre-Testing

Analysis Variable : CaffVAS Tensel

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 19.85 17.00 60 15.31 1.977 15.89 23.81 0 75.00

40min 60 20.97 16.00 60 16.40 2.117 16.73 25.20 0 64.00

120min 60 26.03 23.50 60 18.69 2.412 21.21 30.86 1.00 69.00

Green Blend Pre 60 20.78 17.00 60 16.58 2.141 16.50 25.07 1.00 73.00

40min 60 22.33 18.00 60 19.09 2.464 17.40 27.26 0 67.00

120min 60 22.47 17.00 60 18.28 2.360 17.74 27.19 0 62.00

CGA Pre 60 19.85 16.00 60 15.79 2.039 15.77 23.93 1.00 69.00

40min 60 21.42 19.00 60 16.26 2.099 17.22 25.62 0 63.00

120min 60 24.78 18.50 60 19.14 2.471 19.84 29.73 0 74.00

[00110] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be non-significant (F-value=1.06, p-value=0.35), however the

Treatment* Time interaction was found to be near- significant (F-value=3.03, p-value=0.06).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 1.06 0.3527

Time 1 59 4.74 0.0334 Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment*Time 2 59 3.03 0.0560 baseline 1 59 78.96 .0001

[00111] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 0.2186 0.1693 1.29 0.2018 0.41 -0.1202 0.5574

Placebo CGA 0.03813 0.1855 0.21 0.8379 0.84 -0.3331 0.4093

Green CGA -0.1805 0.1626 -1.11 0.2714 0.54 -0.5058 0.1448 cb 40 Placebo 1 " "11 - ( 1.43 " >( ) ( I. I .-1 N2 -2. .3 0.00S3 0.(13 li -l0.-4N5

ltiiilliSltl -0. 1 1 55

Placebo * 4u Green '"" o " υ.( )( )(ΓΝ( ) 0.1973 0.03 0.9727 0.97 -0.3881 0.4016

Placebo 40 CGA 40 -0.04567 0.2053 -0.22 0.8247 0.97 -0.4565 0.3652

Placebo 120 Green 120 0.4304 0.1825 0.0 r o.(|- 0.06521 0.7957

Placebo 120 CGA 120 0.1219 0.2072 0.59 0.5586 0.56 -0.2928 0.5366

Green 40 Green 120 -0.00837 0.1441 -0.06 0.9539 0.95 -0.2966 0.2799

Green 40 CGA 40 -0.05245 0.1757 -0.30 0.7664 0.97 -0.4041 0.2992

Green 120 CGA 120 -0.3085 0.1981 -1.56 0.1248 0.25 -0.7049 0.08791

CGA 40 CGA 120 -0.2644 0.1464 -1.81 0.0760 0.15 -0.5574 0.02854

[00112] At 120 minutes post-treatment there was a trend towards subjects receiving Green Blend being less tense than those receiving placebo (p-value=0.07). This may be attributable to the significant increase in Caff- V AS Tense score observed from 40 to 120 minutes post-treatment in the placebo group (p-value=0.03) while levels remained relatively stable in the Green Blend group over the same time period. In the CGA group there was also a trend towards an increase in Caff-VAS Tense from 40 to 120 minutes (p- value=0.15).

Headache

Post-Testing

Analysis Variable : CaffVAS Headache2

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 15.03 7.000 60 18.09 2.335 10.36 19.71 0 65.00

40min 60 16.38 9.000 60 19.00 2.453 11.47 21.29 0 78.00

120min 60 21.22 9.500 60 23.05 2.976 15.26 27.17 0 80.00

Green Blend Pre 60 18.98 8.000 60 23.90 3.086 12.81 25.16 0 89.00

40min 60 17.68 8.000 59 22.92 2.983 11.71 23.65 0 81.00

120min 60 19.95 5.000 60 25.91 3.345 13.26 26.64 0 87.00

CGA Pre 60 17.18 10.00 60 17.94 2.317 12.55 21.82 0 64.00 Analysis Variable : CaffVAS Headache2

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

40min 60 18.20 9.500 60 20.24 2.613 12.97 23.43 0 75.00

120min 60 17.18 8.000 60 19.28 2.489 12.20 22.16 0 69.00

[00113] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be non-significant (F-value=1.92, p-value=0.16) whilst the

Treatment* Time interaction was found to be significant (F-value=5.93, p-value<.01).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 1.92 0.1552

Time 1 59 1.93 0.1696 l m.hiH-m --- l i .iH- baseline 1 59 304.80 - .iiiiii i

[00114] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted (using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 0.2117 0.1083 1 .Wi 0.0553 0.17 -ο.οο-Νί, 0.42*4

Placebo CGA 0.1621 0.1211 1.34 0.1856 0.37 -0.08011 0.4043

Green CGA -0.04960 0.1000 -0.50 0.6218 0.62 -0.2497 0.1505

40 1 _i i "", 7v:

"— , S ( >.< > lOS -. >._ " .· ·>

Placebo 40 Green 40 0.1015 0.1140 0.89 0.3772 0.75 -0.1267 0.3296

Green 40 Green 120 -0.01733 0.08968 -0.19 0.8474 0.85 -0.1968 0.1621

Green 40 CGA 40 -0.08580 0.1110 -0.77 0.4427 0.89 -0.3080 0.1364

Green 120 CGA 120 -0.01339 0.1153 -0.12 0.9080 0.91 -0.2441 0.2174

CGA 40 CGA 120 0.05509 0.06121 0.90 0.3718 0.74 -0.06740 0.1776

[00115] From 40 to 120 minutes post-treatment there was a significant increase in headache symptoms in the placebo group (p-value=0.006). At 120 minutes post-treatment subjects receiving Green Blend were found to report significantly less headache symptoms in comparison to placebo (p-value=0.03). Similarly, subjects receiving CGA were also found to report significantly less headache symptoms in comparison to placebo at 120 minutes (p- value=0.04). Overall there was a trend towards subjects receiving Green blend reporting significantly less headache symptoms in comparison to placebo (p-value=0.17). Mental Fatigue

Pre-Testing

Analysis Variable : CaffVAS MentFatiguel

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 21.65 18.00 60 17.08 2.205 17.24 26.06 0 77.00

40min 60 31.72 28.00 60 21.59 2.787 26.14 37.29 1.000 77.00

120min 60 37.08 36.00 60 20.84 2.690 31.70 42.47 1.000 80.00

Green Blend Pre 60 21.73 15.00 60 19.21 2.480 16.77 26.70 0 73.00

40min 60 32.62 26.50 60 23.45 3.028 26.56 38.68 0 92.00

120min 60 37.42 30.00 60 24.63 3.179 31.05 43.78 0 97.00

CGA Pre 60 22.75 14.00 60 20.65 2.666 17.42 28.08 0 87.00

40min 60 29.73 23.50 60 21.39 2.761 24.21 35.26 0 73.00

120min 60 37.77 31.00 60 25.79 3.329 31.10 44.43 2.000 96.00

[00116] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be non-significant (F-value=0.38, p-value=0.69) as well as the Treatment*Time interaction (F-value=0.28, p-value=0.76).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 0.38 0.6856

Time 1 59 14.64 0.0003

Treatment*Time 2 59 0.28 0.7577 baseline 1 59 70.32 <.0001

[00117] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted

(using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green -0.04651 0.3556 -0.13 0.8964 0.90 -0.7580 0.6650

Placebo CGA 0.2735 0.3530 0.77 0.4417 0.88 -0.4329 0.9799

Green CGA 0.3200 0.4131 0.77 0.4417 0.88 -0.5067 1.1467

I'lii ebo 4. ) I'ln cbo 1 20 - I . ( ) (i ( i3 0.441 3 -2.40 0.0 0.04 - Ι Λ 33 -D. I 7 . ;,

Placebo 40 Green 40 J*" -5tl39l 0.4260 -0.33 0.7451 0.75 -0.9916 0.7134

Placebo 40 CGA 40 0.4310 0.4330 1.00 0.3236 0.65 -0.4355 1.2975

Placebo 120 Green 120 0.04613 0.5728 0.08 0.9361 0.94 -1.1001 1.1923

Placebo 120 CGA 120 0.1159 0.4999 0.23 0.8174 0.94 -0.8843 1.1161

Green 40 Green 120 -0.8750 0.5503 -1.59 0.1172 0.12 -1.9763 0.2262

Green 40 CGA 40 0.5701 0.4722 1.21 0.2321 0.49 -0.3748 1.5151

Green 120 CGA 120 0.06981 0.6071 0.11 0.9088 0.94 -1.1450 1.2846

CGA 40 C CA 1 20 - 1 ,.^54 Q .4 Q -2M Q .0 Q 44 P.P . -2.MX* -0.44 M . [00118] No significant treatment effects were observed, although significant increases in mental fatigue were observed from 40 to 120 minutes in both the Placebo (p- value=0.04) and CGA group (p-value=0.01).

Post-Testing

Analysis Variable : CaffVAS MentFatigue2

Lower 95% Upper 95%

Std Std CL for CL for

Treatment Time Obs Mean Median N Dev Error Mean Mean Minimum Maximum

Placebo Pre 60 37.58 35.00 60 24.06 3.106 31.37 43.80 0 94.00

40min 60 44.77 42.00 60 24.12 3.114 38.53 51.00 0 90.00

120min 60 52.02 59.00 60 25.01 3.228 45.56 58.48 0 94.00

Green Blend Pre 60 38.22 36.50 60 24.32 3.139 31.94 44.50 0 87.00

40min 60 45.31 45.00 59 25.36 3.302 38.70 51.91 1.000 92.00

120min 60 48.67 56.00 60 25.51 3.294 42.08 55.26 2.000 94.00

CGA Pre 60 37.22 34.50 60 23.72 3.062 31.09 43.34 0 80.00

40min 60 45.62 46.50 60 24.02 3.101 39.41 51.82 1.000 91.00

120min 60 53.55 57.50 60 24.00 3.098 47.35 59.75 0 94.00

[00119] Mixed ANCOVA adjusting for baseline score and considering time, treatment and their interaction as independent variables were fitted. The main effect for treatment was found to be non-significant (F-value=0.88, p-value=0.42) as well as the Treatment*Time interaction (F-value=0.72, p-value=0.49).

Type 3 Tests of Fixed Effects

Effect Num DF Den DF F Value Pr > F

Treatment 2 59 0.88 0.4183

Time 1 59 15.82 0.0002

Treatment*Time 2 59 0.72 0.4886 baseline 1 59 72.23 <.0001

[00120] Differences of Least Square Means were calculated between the three treatments as well as the interaction of Treatment* Time. Both unadjusted and adjusted

(using Hommel correction) p-values are reported.

Treat Time Treat Time Estimate Std Error t Value Pr > |t| Adj P Lower Upper

Placebo Green 1.7074 2.6265 0.65 0.5182 0.52 -3.5482 6.9629

Placebo CGA -1.3548 2.1087 -0.64 0.5230 0.52 -5.5743 2.8646

Green CGA -3.0622 2.3448 -1.31 0.1966 0.52 -7.7542 1.6298

P vfc, 4. ) vho 1 2. ) -.:5<»<» 2*244 -Vo <U»<»^ "·<>: - L\S» I .< - 1 .99* 1

Placebo 40 Green 40 -0.2171 3.8589 -0.06 0.9553 0.96 -7.9388 7.5045

Placebo 40 CGA 40 -1.0132 3.0625 -0.33 0.7419 0.96 -7.1412 5.1148

Placebo 120 Green 120 3.6319 2.5142 1.44 0.1539 0.31 -1.3989 8.6627

Placebo 120 CGA 120 -1.6965 2.3904 -0.71 0.4807 0.48 -6.4797 3.0866

Green 40 Green 120 -3.4010 2.6572 -1.28 0.2056 0.21 -8.7180 1.9160

Green 40 CGA 40 -0.7960 3.4962 -0.23 0.8207 0.96 -7.7919 6.1998

[00121] There was a significant increase in ratings of mental fatigue from 40 to

120 minutes in both placebo (p-value=0.02) and CGA groups (p-value=0.01), whilst levels remained relatively unchanged in the Green Blend group over this time period. At 120 minutes post-treatment there was a trend towards subjects receiving Green Blend were reporting less mental fatigued in comparison to those receiving CGA (p-value=0.13).




 
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