GET YOUR BRAIN IN THE GAME

INTEGRATING COGNITIVE

SUPPORT IN SPORTS &

ACTIVE NUTRITION

Presented by Jeremy Appleton, ND - Director of Medical & Scientific Affairs, PLT Health Solutions2020 Sports Nutrition Summit – San Diego CA

www.plthealth.com

2

“Continuous non-linear interactions between system components support the exploration of fluent and flexibly creative performance solutions by athletes and sports teams.”

EXERCISE AND COGNITION

3

• Moderate to vigorous exercise improves cognition1

• Processing speed• Memory • Executive function

• Physical activity is directly related to high levels of Emotional Intelligence2

• Physical activity physically remodels white matter3

CO

GN

ITIVE HEALTH

IN SPO

RTS

1. Med Sci Sports Exerc. 2019 Jun;51(6):1242-51.2. Behav Sci (Basel). 2019 Apr 24;9(4). pii: E44. 3. Pediatrics. 2019 Oct;144(4). pii: e20184032.

EXERCISE AND MENTAL HEALTH

4

• Exercise improves mental disorders1

• Depression, Anxiety, Schizophrenia, ADHD• Eating disorders, PTSD, Substance abuse

• Greater amounts of physical activity reduce risk of cognitive impairment, including Alzheimer’s disease2

• Alzheimer’s benefitted by exercise via mTOR3

CO

GN

ITIVE HEALTH

IN SPO

RTS

1. Sports Med. 2020 Jan;50(1):151-170.2. Prog Cardiovasc Dis. 2019 Mar-Apr;62(2):94-101.3. Int J Mol Sci. 2019 Mar 29;20(7). pii: E1591.

THE NEED FOR SUPPORT

5

• Brain-body interactions in sport are difficult to study1

• Hypoxia counteracts exercise-induced improvements in cognition2

• Prior cognitive exertion is associated with a subsequent decline in physical performance3

• Mental fatigue impairs sport performance4-7

CO

GN

ITIVE HEALTH

IN SPO

RTS

1. Prog Brain Res. 2018;240:247-267.2. Scand J Med Sci Sports. 2019 Oct 12. doi: 10.1111/sms.13573.3. Sports Med. 2019 Dec 24. doi: 10.1007/s40279-019-01204-8. 4. J Sci Med Sport. 2019 Jun;22(6):723-728. 5. Eur J Sport Sci. 2019 Nov;19(10):1367-1376.6. Sports Med. 2011 Apr 1;41(4):307-28. 7. Prog Brain Res. 2018;240:291-315.

DIFFERENT TYPES OF COGNITIVE SUPPORT ARE AVAILABLE

SATIETY

6

SCIENTIFICALLY SUPPORTINGA RANGE OF BENEFITS

THINKING BEYOND THE SAME OLD COGNITIVE INGREDIENTS

7

Different benefit areas. Different mechanisms of action. All supported by science.

Targeted-releaseCAFFEINE

Bacopa monnieri

Crocus sativus

Sceletium tortuosum

Mangifera indica

• Primarily studied non-elderly populations (18-65), with a focus on work and school performance

• Synapsa: 4 chronic clinicals, 3 acute clinicals, 4 pre-clinicals • Dose is 320 mg (chronic) or 640 mg per day (acute)• Demonstrated outcomes: faster information processing, faster

learning, decreased forgetfulness, improved memory consolidation, and better multi-tasking accuracy

BACOPA MONNIERI (SYNAPSA, CDRI08)Review and Research Highlights

CLIN

ICAL R

ESEARC

H

8

Psychopharmacology. 2001; 156:481-484.Neuropsychopharmacology. 2002; 27:279-281.Indian Journal of Psychiatry. 2006; 48:238-242.Phytotherapy Research. 2008; 22:1629-1634..Human Psychopharmacology. 2001; 16:345-351.Phytotherapy Research. 2012; 27:1407-1413.Phytotherapy Research. 2013 21 Jun.

These studies focus on healthy adults from 18 to 65

What problems could it address in sports and active nutrition?

VALUE PR

OPO

SITION

• Improve stamina by preventing depletion of key neurotransmitters

• Decreasing adverse effects on sports performance of “prior cognitive exertion”

• Anti-inflammation• Synergy with exercise’s beneficial

effects on memory• Prevent hypoxia through increased

cerebral blood flow

MECHANISMS/ACTIONS• NOOTROPIC• ANTI-INFLAMMATORY• ANTIOXIDANT• NEURO-PROTECTIVE• METAL CHELATION• BETA-AMYLOID

REDUCTION• INCREASED CEREBRAL

BLOOD FLOW• ADAPTOGEN/↓CORTISOL

BACO

PA MO

NN

IERI

9

BACOPA MONNIERI (SYNAPSA, CDRI08)

Put on your game face: Bacopa is an adaptogen that enhances mental focus

CLIN

ICAL R

ESEARC

H

10

BACOPA MONNIERI

• “Prevention of neurotransmitter depletion is the cornerstone of adaptogenicstamina enhancement, both physical and mental”

• In animals, Bacopa attenuated stress-induced depletions of norepinephrine, dopamine, and 5-HT1

• In humans, Bacopa (Synapsa) has been shown to improve focus and concentration while reducing mental stress and cortisol levels2,3 1. J Ethnopharmacol. 2007 May 22; 111(3):671-6.

2. Phytother Res. 2013; 21 Jun.3. Psychopharmacology. 2001; 156:481-4.

11

Review and research highlightsSCELETIUM TORTUOSUM (ZEMBRIN)

• Sceletium is a unique selection of South African botanical medicine with over 300 years of documented use

• Unlike Kanna, Zembrin is well-studied and well-characterized chemically, with a unique alkaloid profile, rich in mesembrenone and low in mesembrine

• Demonstrated clinical efficacy for physical and emotional stress, improved/decreased anxiety, and enhanced mental focus.

• Zembrin: 3 clinical trials; 5 pre-clinical studies.

SC

ELE

TIUM

TOR

TUO

SU

M (ZEM

BRIN

)

SCELETIUM TORTUOSUM (ZEMBRIN)

12

• Reduced anxiety-related activity in amygdala on fMRI1

• Increased mental focus2

• Improved cognitive set flexibility• Improved executive function

• Fast-acting: documented effects within 2 hrsafter a single dose1

• Synergy with exercise’s beneficial effects on depression, emotional regulation, mood and sleep

• Adoption by bodybuilders, stacking with forskolin to potentiate lipolysis, fat loss

SC

ELE

TIUM

TOR

TUO

SU

M (ZEM

BRIN

)

What problems could it address in sports and active nutrition?

MECHANISMS/ACTIONS• 5-HT TRANSPORT

INHIBITION (SSRI)3

• PDE4 INHIBITION3

• HAM-D2

• Improved sleep• HAM-D improved mood• HAM-D improved work

performance

1. J Ethnopharmacol. 2011 Oct 11;137(3):1124-9. 2. Evid Based Complement Alternat Med. 2014:6820143. Neuropsychopharmacology. 2013;1-9.

Evid Based Complement Alternat Med. 2014:682014.

SCELETIUM AND STRESS MANAGEMENT

13

Better impulse control + Goal-directed behavior

SC

ELE

TIUM

TOR

TUO

SU

M (ZEM

BRIN

)

13

35.4

60.2

49.7

Cognitive Set Flexibility

*p < 0.022 vs. placebo

*

Baseline PlaceboZembrin®

mea

n pe

rcen

tiles

13

*p < 0.032 vs. placebo

36.8

60.8

50.1

Executive Function

3 weeks

*

mea

n pe

rcen

tiles

Baseline PlaceboZembrin®

CROCUS SATIVUS (SAFFRON, SUPRESA) CR

OC

US

SATIV

US

(SAFFRO

N, SU

PRESA)

14

Review and Research Highlights

• Clinical trials on mood, depression 1

• Clinical trial (Supresa) on weight loss and snacking reduction 2

• Standardized extract with specific fingerprint of bioactives

• Safranal, Crocin, Picrocin

1. Many studies, e.g., Phytother Res. 2005; 19:148-151. 2. Nutr Res. 2010;30:305-13.

CR

OC

US

SATIV

US

(SAFFRO

N, SU

PRESA)

15

What problems could it address in sports and active nutrition?CROCUS SATIVUS (SAFFRON, SUPRESA)

• Synergize with the well-documented benefits of exercise on depression, and eating disorders

• Weight management and crave control,1 especially in athletes where small differences in body weight are influential

• Prevent anxiety- and depression-triggered reactive hyperphagia (compulsive overeating)

MECHANISMS/ACTIONS• 5-HT TRANSPORT INHIBITION

(SSRI)2

• ANTIDEPRESSANT EFFECTS3

• MOOD ELEVATION AND CRAVE CONTROL 1

• NEUROPROTECTION AND ANTIOXIDANT 4

• NEURO ANTI-INFLAMMATORY4

• MODULATES REWARD CENTERS IN THE BRAIN 4

1. Nutr Res. 2010;30:305-13.2. Arzneim-Forsch Drug Res. 1995;45: 145-8.3. Many studies, e.g., Phytother Res. 2005; 19:148-151. 4. Avicenna J Phytomed. 2015;5(5):376-91.

CROCUS SATIVUS: SUPRESA CLINICAL TRIAL CR

OC

US

SATIV

US

(SAFFRO

N, SU

PRESA)

16

Clinically evaluated for ability to reduce snacking and increase satiety

Randomized, Double-Blind, Placebo-Controlled Clinical Trail of Saffron Extract

• 60 healthy women 25-45 years old, 25-28 BMI (overweight)

• 8-week supplementation with SUPRESA® or placebo

• 2x/day at breakfast and dinner, 176.5 mg total• Unrestricted calorie intake• Primary endpoint: body weight (and difference

from baseline)• Other endpoints: snacking events, sensations

of hunger, body fat, lean mass, BMI

Mangifera indica (mango leaf) extract standardized to ≥ 60% mangiferin

MANGIFERA INDICA (ZYNAMITE, MANGIFERIN) MA

NG

IFER

A IND

ICA (ZYN

AMITE)

17

Review and Research Highlights

1. Nutrients. 2019;11:344. 2. Front Physiol. 2018;9:740.3. Nutrients. 2019; 11: 2592.4. Calbet JAL et al, 2019. Data on file.5. Dimpfel W et al, 2016. Data on file.6. Koch, 2019. Data on File.7. Koch et al, 2017. Data on file.

• For mental and physical energy; experiential and fast-acting

• Standardized to mangiferin, a xanthone• 3 preclinical studies, 7 clinical trials

• Four clinicals on sports performance and recovery1-4

• Three clinicals on cognition5-7

• Studied alone, and in combination with flavonoids and phospholipids Demonstrated synergy with quercetin

MA

NG

IFER

A IND

ICA (ZYN

AMITE)

18

What problems could it address in sports and active nutrition?MANGIFERA INDICA (ZYNAMITE, MANGIFERIN)

• Improved oxygen extraction from muscles during workout

• Faster reaction time and improved calculation performance (mental energy)

• Enhanced mean and peak power output on cycle ergometer, including in exhaustion and EIMD scenarios (physical energy)

• Reduced muscle soreness and accelerated recovery

• No changes in HR variability or BP

MECHANISMS/ACTIONS• ANTIOXIDANT• ANTI-INFLAMMATORY• COMT INHIBITION• TRADITIONAL USE AS A TONIC

FOR EXHAUSTION AND FATIGUE

• ELICITS BRAIN WAVE CHANGES IN ANIMALS AND HUMANS

• MENTAL STIMULATION SIMILAR TO CAFFEINE, WITHOUT ADVERSE CAFFEINE-EFFECTS

MANGIFERA INDICA (ZYNAMITE) MAN

GIFER

A IND

ICA (ZYN

AMITE)

19

Push beyond limits. Expand what’s possible.

COGNITIVE SPORTSENHANCED MENTAL ENERGYFASTER REACTIONSBETTER COGNITIVE PERFORMANCENON-STIM

ENHANCED POWER OUTPUTFASTER REACTION TIMES

IMPROVED COGNITIONACCELERATE RECOVERY

TARG

ETED-R

ELEASE CAFFEIN

E (zümXR

)

20

Review and Research HighlightsTARGETED-RELEASE CAFFEINE (zümXR)

• Anti-fatigue via adenosine receptor blockade• Widely used by athletes and non-athletes (80% of adults

consume caffeine)• Improved alertness, vigilance, attention, reaction time,

attention and motivation• Ergogenic effects on exercise performance are well-

established and well-replicated across a broad range of exercise modalities

TARG

ETED-R

ELEASE CAFFEIN

E (zümXR

)

21

What problems could it address in sports and active nutrition?TARGETED-RELEASE CAFFEINE (zümXR)

Immediate-release caffeine has a PK problem

• Caffeine is effective for workouts, but 60% surveyed say it doesn’t last long enough

• Crash too quickly, effects wear off too quickly for sustained workouts

• Stimulation desired by some, but 26% complain that an effective dose creates unpleasant “jitters”

TARGETED-RELEASE CAFFEINE (zümXR)

22

CUSTOMIZE TO YOUR PREFERRED ENERGY PROFILE

TARG

ETED-R

ELEASE CAFFEIN

E (zümXR

)

Combining conventional anhydrous caffeine with zümXR Extended Release Caffeine

CAFFEINEEXPERIENCE

TIME (Hours)

Extended workout

Pre-Workout

Morning Pick Me Up

TARGETED RELEASE CAFFEINE (zümXR)

23

TARG

ETED-R

ELEASEC

AFFE

INE

(zümXR

)

EXTENDED RELEASE & DELAYED RELEASE PROFILES• Total caffeine payloads above 80% • Composed of GRAS ingredients• Highly adaptable ingredient• Heat stable• Wide application base: recommended for use in supplements, stick packs, powders, gummies & gels

Two unique caffeine solutions

DELAYED RELEASE PROFILE*

% C

AFFE

INE

REL

EASE

TIME

EXTENDED RELEASE PROFILE*

% C

AFFE

INE

REL

EASE Immediate

zümXR Extended

* Charts are for illustrative purposes

TIME

zümXR Delayed

Immediate

THE COMMERCIAL OPPORTUNITY

25

MAKE YOUR FORMULATIONS EXPERIENTIAL• Easier first-time sale• Repeat business

GIVE YOUR CUSTOMERS WHAT THEY WANT

DIFFERENTIATE YOUR PRODUCTS• Gain/protect market share• Increase pricing

BE A LEADER IN INNOVATION• Enhance your brand

CO

NC

LUSIO

NS

Adding cognitive ingredients to sports and active nutrition products

GET YOUR BRAIN IN THE GAME

INTEGRATING COGNITIVE

SUPPORT IN SPORTS &

ACTIVE NUTRITION