Essential Nutrients, Phytochemicals and Human Brain Function

Prof. David Kennedy

[email protected]

www.nutrition-neuroscience.com

Essential Nutrients, Phytochemicals

and Human Brain Function

• Focus on ‘safe’ treatments: essential nutrients, phytochemicals, functional foods and dietary components thought to improve mood and/or cognition

PLANT SECONDARY METABOLITES

• Ginkgo biloba • Panax ginseng • Ginkgo-ginseng combination • Melissa officinalis • Salvia officinalis • Salvia lavandulaefolia • Valerian • Guarana • Ginkgo-phosphatidylserine • Cocoa polyphenols • Resveratrol • EGCG • Caffeine • Theanine ESSENTIAL NUTRIENTS • Oxygen • Glucose • Water

• Polyunsaturated fatty acids

• Vitamins

• Minerals

Our Research

• Vitamin B6 - 10% of males and 11% of females

• % iron saturation indicating anaemia 7% males and 16% females -• Vitamin C - 5% males 3% females

• Folate - 4% males, 5% females

• Vitamin B 2 (riboflavin) – 66% of sample deficient (?)

25% males 16% females

13% males 11% females

Vitamins and Minerals

• Intrinsic to every aspect of brain function • Epidemiological evidence suggestive

• Survey and analyte data suggest deficiencies • Intervention trial evidence scant

Multivitamins and Mental performance

Design: Randomised, placebo-controlled, double-blind

study assessing 33 days administration with

multi-vitamins/minerals.

Outcomes: subjective feelings of stress (Perceived

Stress Scale), general health (GHQ), mood (POMS) and

mental performance (CDB, Stroop, Executive tasks) .

Participants: 210 healthy male participants (30 – 55

years) in full time work.

Vitamins: Amount Minerals: Amount Vitamin B₁ 15 mg Calcium 100 mg Vitamin B₂ 15 mg Magnesium 100 mg Vitamin B₆ 10 mg Zinc 10 mg Vitamin B₁₂ 10 mcg Vitamin C 500 mg Biotin 150 mcg Folic Acid 400 mcg Nicotinamide 50 mg Pantothenic acid 23 mg

Day -2/3 Lab visit

Day -2/3

Day -1 Day 7 Day 14 Day 21 Day 28

Day 33 +/-Lab visit L a b o ra to ry S tu d y Day 33 Treatment Day 1

Commences Mobile Phone Battery before and after a day’s work

M o b il e P h o n e S tu d y

Laboratory Study

Serial subtractions

892

*** Subtract 3 or 7 from

that starting number. The response shows

as asterisks in the box A random number between 800 – 1000 is generated by the computer as a starting number Enter key * ** ****** ***

Hold this new number in memory

RVIP

Task is to press the space bar whenever you see three consecutive odd or even digits Numbers appear in the middle of the screen at a rate of 100 per minute

6

6

6

6

1

1

1

1

4

4

9

0

0

0

0

9

9

8

6

8

1

1

3

3

5

5

6

6

6

9

6

7

7

7

5

5

6

5

7

7

5

7

4

3

4

3

8

2

4

4

4

6

7

6

2

5

3

8

5

3

3

3

7

1

1

4

2

2

Results

Perceived Stress Scale GHQ-12 Day 33 S c o re 20 22 24 26 28 30 POMS Vigour

POMS Total Score

F(1, 205)=4.52, p<0.05 F(1, 205)=4.25, p<0.05 F(1, 196)=6.03, p<0.05 * * * Day 33 S c o re 50 55 60 65 70

POMS Total Score

F(1, 196)=3.77, p=0.05

Day 33 N u m b e r 38 39 40 41 42 43 44 1 2 3 4 5 6 24 25 26 27 28 29 30 N u m b e r Serial 7s correct Serial 3s correct Day 33 m m 40 45 50 55 60 Mental Tiredness Day 33 50 52 54 56 58 60 m m Mental Fatigue F(1, 199)=1.93, p=0.09 F(1, 198)=4.90, p<0.05 F(1, 199)=4.05, p<0.05 F(1, 198)=2.90, p=0.09 ***** t t * * Repetition of task Placebo Berocca

Mobile Phone Study: Kennedy et al (2011) Human Psychopharmacology Healthy adult females: Haskell et al (2010) Human Psychopharmacology Children: Haskell et al (2008) British Journal of Nutrition

Omega-3 Fatty acids

Kennedy et al (2008) No cognitive effects of 8 weeks administration in children Jackson et al (2011) No cognitive effects of 12 weeks administration of high DHA or

high EPA fish oil in healthy adults

Jackson et al (2012) assessed the effects of 12 weeks administration of two

doses (1 g, 2 g) of DHA rich fish oil on the cerebral blood flow response to neural activation in 65 healthy adults.

Oxygenated Haemoglobin

Cerebral Blood

Improved Secondary

memory Improved Mood

Acetylcholinesterase -3 -2 -1 0 % i n h ib it io n 30 40 50 60 70 80 90 Concentration (log[mg/mL]) COMPOUND RETENTION TIME (MIN) PERCENTAGE COMPOSITION a-Pinene 9:56.04 5.6 Camphene 10:18.99 5.7 Sabinene 10:55.21 0.3 b-Pinene 11:00.31 5.1 b-Myrcene 11:17.65 0.6 p-Cymene 12:05.09 0.5 Limonene 12:11.21 4.2 1,8-Cineole 12:14.78 36.4 Linalool 13:37.41 0.4 Camphor 14:36.07 37.0 endo-Borneol 15:00.04 1.2 a-Terpineol 15:24.52 Tr Linalyl acetate 16:25.22 0.7 Bornyl acetate 17:02.97 0.7 Unidentified 17:04.50 1.2 Unidentified 19:16.10 0.1 Unidentified 19:46.19 0.1 A. B. C.

Methodology

• Design

– 36 healthy young participants

– Randomised, placebo controlled, double-blind, balanced crossover

• Two matched treatments

– placebo; 50 µl S. lavandulaefolia essential oil

baseline 1 hour 4 hours

basele

Testing days: assessment

(placebo + active treatments)

Treatment

(placebo + active treatments)

repeated for second treatment 7 days later

Minutes 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 70 10 20 30 40 50 60 80 90 0 Cognitive assessment

Shopping lists presentation Picture presentation

Name -to - face presentation Immediate word recall

Immediate name -to -face recall Telephone numbers task

Simple reaction time Choice reaction time

Delayed name -to -face recall Delayed word recall

Delayed word recognition Delayed picture recognition Bond-Lader Mood Scales

Bond-Lader Mood Scales State-Trait Anxiety Inventory

Minutes 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 3 s, 7 s, R V IP , v a s 70 10 20 30 40 50 60 80 90 0 Cognitive assessment

-2 -1 0 1 2

1 hour post-dose 4 hours post-dose

**

Alert

Interaction (assessment X treatment): F(1, 35)=2.21, P=0.003

C o m b in e d m m Salvia Placebo

MOOD

0 10 20 30 40 Mental Fatigue Salvia Placebo 1 2 3 4 5 6 1 2 3 4 5 6 -2 0 2 4 6 8 1 2 3 4 5 6 1 2 3 4 5 6 * * * ** ** ** ** * ** ** ** ** T o ta l n u m b e r o f s u b tr a c ti o n s M e n ta l F a ti g u e (m m ) Serial 3s 1 hour post-dose repetitions 4 hour post-dose 4 hour post-dose

• Resveratrol – phytoalexin polyphenol

• Attributed with a plethora of health benefits in humans (but low bioavailability in mammals)

• Increases peripheral and cerebral blood flow in rodents • Anti-oxidant and promoter of Nitric Oxide synthesis

• Nitric Oxide is a key modulator of neurovascular coupling between neural activity and blood flow

cerebral blood flow

Oxygen extraction

n g /m L 0 200 400 600 800 Resveratrol 250 mg 500 mg 250 mg 500 mg 250 mg 500 mg Resveratrol glucuronide Resveratrol sulfate

Pre-treatment 45 min 90 min 120 min Time with respect to treatment

Start of post dose tasks.

End of post dose tasks.

Summary and conclusions

It is clear from our research that the populations of economically

developed societies can benefit from augmented levels of the essential nutrients that they should be consuming in a normal healthy diet.

Furthermore many ‘voluntarily’ consumed plant derived chemicals can have specific effects on brain function in terms of modulation of physical parameters or cognitive performance.

Dr Crystal Haskell Dr Emma Stevenson Dr Philippa Jackson Joanne Gee Bernadette Robertson Rachel Veasey Anthony Watson Fiona Dodd Emma Wightman Ms Jade Elliott Javier Gonzalez Anthea Milne

And our many collaborators