Natural Products for

Stress Reduction
Michael T. Murray, N.D.

 The biology of the stress response

 Is stress affecting your life?
 Comprehensive stress management
 Emerging category leaders in stress,
anxiety and insomnia
 What exactly is
stress?
 Stress refers to a number of biological
changes that can be triggered by any
disturbance to our normal physiology.

 Stress is produced by an exposure to a

“stressor.”

 Stress is neutral – the body responds the

same to positive or negative stressors.

 The stress response is entirely

individualized.
“No one can live without experiencing
some degree of stress all the time. You
may think that only serious disease or
intensive physical or mental injury can
cause stress. This is false. Crossing a
busy intersection, exposure to a draft, or
even sheer joy are enough to activate the
body’s stress mechanisms to some
extent. Stress is not even necessarily bad
for you; it is also the spice of life, for any
emotion, any activity causes stress. But,
of course, your system must be prepared
 General Adaptation
Syndrome
Three stages:
1. Alarm stage
- Emergency reaction (fight-or-
flight)
1. Resistance stage
- Coping and adaptation
1. Exhaustion stage
- Termination of stress response
and onset of stress pathology
 The alarm phase or
“fight-or-flight” response
2-step physiological process:
1. Activation of the sympathetic
nervous system
- Quick response system, within
seconds
- Release of epinephrine
(adrenaline)
 The alarm phase or
“fight-or-flight” response
2-step physiological process:
2. HPA Axis (hypothalamic-
pituitary-adrenal axis)
– Slower response system,
minutes to hours
– Release of cortisol
 Is excessive
stress affecting
your life?
 Stress is linked to 80% of all
illnesses
 Angina  Irritable bowel
 Asthma syndrome
 Autoimmune  Lowered immunity
disease  Menstrual irregularities
 Cancer  Non-ulcer dyspepsia
 Cardiovascular  Obesity
 PMS
disease
 Rheumatoid arthritis
 Colds
 Ulcerative colitis
 Depression
 Ulcers
 Diabetes (Type 2)
 Headaches
 High blood
pressure
 PHYSICAL SYMPTOMS
Sleep changes Dizziness
Fatigue Fainting
Digestion Sweating &
changes trembling
Loss of sexual Tingling hands
drive & feet
Headaches Breathlessness
Aches and pains Palpitations
Infections Missed
Indigestion heartbeats
 MENTAL SYMPTOMS
Lack of concentration
Memory lapses
Difficulty in making decisions
Confusion
Disorientation
Nervousness, anxiety, panic
attacks
 BEHAVIOURAL SYMPTOMS
 Appetite changes - too much or too little
 Eating disorders - anorexia, bulimia
 Increased intake of alcohol & other drugs
 Increased smoking
 Restlessness, fidgeting, nail biting, etc.
 Hypochondria
 Deterioration of personal hygiene and
appearance
 EMOTIONAL SYMPTOMS

Bouts of depression
Impatience
Fits of rage
Tearfulness
Deterioration of personal
hygiene and appearance
 Comprehensive Stress
Management
 Develop an anti-stress attitude and
personality
Engage in an anti-stress lifestyle
Support an anti-stress physiology
Utilize appropriate natural products
 Explanatory style:
A key factor in stress management
Measure: Optimist
Pessimist
Permanence
negative events temporary
permanent
positive events permanent
temporary
Pervasiveness specific
universal
Hope hopeful
hopeless
Personalization
 Time Management
A key factor in stress management
Set priorities.
Organize your day.
Delegate authority.
Tackle tough jobs first.
Be prepared for meetings.
Avoid putting things off.
Plan ahead.
Don’t be a perfectionist.
 Good relationships
A key factor in stress
management
Focus on becoming a
good listener.
Be an active listener.
Be a reflective listener.
Wait to speak.
Pay attention to non-
verbal clues.
 Physical Exercise
A key factor in stress
management
 Uses up excess energy released by
the ‘Fight or Flight’ reaction.
 Improves blood circulation
 Lowers blood pressure
 Clears the mind of worrying thoughts
 Improves self image
 Improves sleep quality
 Relaxation Exercises
A key factor in stress
management
Promote the “Relaxation Response”
Popular techniques:
Deep breathing exercises
Meditation
Prayer
Progressive relaxation
Self-hypnosis
Biofeedback
 7 Key Dietary Principles
of the Optimal Health
Eat
 Eat to
to support Diet
support blood
blood sugar
sugar control.
control.
Eat
 Eat aa rainbow
rainbow assortment
assortment of
of fruits
fruits and
and
vegetables.
vegetables.
Reduce
 Reduce exposure
exposure to to pesticides.
pesticides.
Do
 Do not
not over
over consume
consume animal
animal foods.
foods.
Eat
 Eat the
the right
right types
types of
of fats.
fats.
Keep
 Keep salt
salt intake
intake low,
low, potassium
potassium intake
intake
high.
high.
Drink
 Drink sufficient
sufficient amounts
amounts of of water
water each
each
day.
day.
 Foundational
Supplements for Good
Health
 High Potency Multiple
 MultiStart
 Greens Drink
 Enriching Greens
 High Quality Fish Oils
 RxOmega-3 Factors
 Omega-3 Fatty Acids:
Practical
Recommendations
 Use the highest quality fish oils
providing at least a 60% concentration
of EPA and DHA.
 For general health, take 1,000 mg of
EPA/DHA daily.
 For inflammatory and other
therapeutic indications increase
dosage to 3,000 mg of EPA/DHA daily.
 Limit fish consumption to no more
than two servings per week.
 Fish Oils Effective in
Borderline Personality
1,000 mg of EPA daily for eight weeks shown to be effective in
reducing major symptoms in double-blind study.

Characteristics of Borderline Personality Disorder

 Unstable personal relationships.
 Frantic efforts to avoid real or imagined abandonment.
 Markedly and persistently unstable self-image or sense of self.
 Impulsivity in at least two areas that are potentially self-
damaging (e.g., spending, sex, substance abuse, etc.)
 Recurrent suicidal behavior, gestures, or threats, or self-
mutilating behavior.
 Tremendous mood swings.
 Chronic feelings of emptiness.
 Inappropriate, intense anger or difficulty controlling anger.

Am J Psychiatry.
Sedative/Hypnotic Drugs
 alprazolam (Alprazolam, Xanax)
 chlordiazepoxide (Librium)
 diazepam (Valium)
 eszopiclone (Lunesta)
 flurazepam (Dalmane)
 quazepam (Doral)
 temazepam (Restoril)
 triazolam (Halcion)
 zolpidem tartrate (Ambien)
Sedative/Hypnotic Drugs
 Highly addictive
 Very poor candidates for long-term use.

 Side effects are common:

Dizziness, drowsiness, and impaired coordination
Depression
Memory and cognitive impairment
Potentially dangerous:
 Should not be driving while on these drgus.
 Alcohol consumption while on these drugs can be fatal.

Sales of sedative/hypnotics have increased by

over 35% in the last year!!!
 Traditional Category Leaders
for Stress, Anxiety, and
Insomnia
Stress
Panax and Siberian ginseng
Adaptogens
Diverse antistress effects
Anxiety
Kava – removed from the marketplace
St. John’s wort – tainted by bad press
Insomnia
Melatonin – not a panacea
Valerian – can produce “hangover”
 Emerging Category
Leaders for Stress,
Anxiety, and Insomnia
Stress
Sensoril (Withania somnifera extract)
Pharma GABA
Anxiety
5-HTP
L-theanine
Insomnia
Combination of 5-HTP, L-theanine,
and melatonin
 Sensoril®
Sensoril® a proprietary
extract of Withania somnifera
(Ashwaganda)
Protected under United
States Patents 6,153,198 and
6,713,092.
Patents cover the extraction
process and the composition
of the extract.
 Sensoril® Clinical Trial
Interim Report
Improvements in Subjective Features
 Increased Energy
 Reduction in Fatigue
 Better Sleep
 Less Irritability
 Greater Levels of Concentration/Focus
 Reduction of Stress Symptoms
 Increased General Feeling of Overall
Wellbeing
 Sensoril® Clinical Trial
Interim Report
Improvements in Objective Features
Statistically significant decreases
in:
 Cortisol levels (by up to 26%)
 Fasting blood sugar
 Total cholesterol, LDL, VLDL and
triglycerides
Statistically significant increases in:
 HDL (good cholesterol)
 DHEA
Gamma AminoButyric Acid
(GABA)
NH 2
COOH

Pharma-GABA
R
 Production of Pharma-
GABA™
Glutamic Acid, Glucose,
Yeast Extract
and other ingredients
⇓
fermentation
⇓
sterilization
⇓
filtration
⇓
Spray drying
⇓ Lactobacillus hilgardii K-3

Pharma-GABA80
(80% GABA powder) ）
 Clinical trial #1
1. Subject: 8 people with fear of heights, 5 Male; 3 Female

2. Method of loading stress: walk across the bridge with 50M height

3. Evaluation methods: Salivary IgA

4. Test schedule Sample saliva Sample saliva

Before start Outward start Homeward start End

Saliva ○ ○ ○
collections
Anti-Stress Effect of Pharma-GABA

Change of IgA level in saliva under stress

350 Control
GABA
300

250
総 IgA量（μ g）

200
Total IgA

150

100

50

0
Before
出発前 Center
真ん中of After
終了
start bridge returning
Clinical Trial #2
1. Subjects: 13 people; 7 male; 6 Female
2.Method of loading stress: Crossing a suspension bridge, 50m height

3.Evaluation methods: Psychological test (Profile of Mood States [POMS])

Salivary Chromogranin A

4.Schedule Saliva sampling

Saliva sampling

Before Start Outward start Homeward start End

Saliva ○ ○ ○
POMS ○ ○
 POMS Test Result of Loading Stress

GABA Confusion
Control
Fatigue

Vigor

Anger-Hostility

Depression-
Dejection

Tension-
Anxiety
-8 -6 -4 -2 0 2 4
Reduced 　　　←→　　　 Increased
Stress and Chromogranins A
(CgA) in Saliva
CRH Hypothalami
Stress c area
Adenohypoph
ACTH ysis

Adrenal Adrenal
medulla cortex
CgA Cortisol
・ saliva:mental stress ・ gluconeogenesis
marker enhancement
・ blood plasma:tumor ・ protein and fat
marker metabolism
・ immunity
enhancement
&
inflammation
constraint
 Test result – Chromogranin A

CgA variability rate% 140

120

100

80
Control
60
GABA
40

20

0
Before Mid point After
Effect of GABA on autonomic nervous system

diameter of pupil

large small
sympathetic parasympathetic
nerve nerve
Diameter of pupils and heart beat rate were measured before intake and
30 min., 60min., and 90 min. after intake of GABA (100mg), to identify
the effect of GABA on autonomic nervous system.
 Effect of Pharma-GABA on control
dextrin 100mg
autonomic nervous system GABA 100mg
Diameter of pupil Heartbeat rate
1.10 1.04
1.05
1.00
1.00
0.96
0.95
0.90 0.92
*
0.85 0.88
0 30 60 90 (min.) 0 30 60 90

Diameter of pupils and heart beat rate were measured before intake and
30 min., 60min., and 90 min. after intake of GABA (100mg), to identify
the effect of GABA on autonomic nervous system.
Clinical trial with GABA-Coffee
Test substance
○mineralwater 280ml
○non GABA-containing coffee 280ml
○GABA-containing coffee 280ml 　 (28mg of
GABA)

Test subjects: 19 males; average age:29

Method of stress loading: Uchida Kraepelin test (Japan

Mental Technic Laboratory)

Measured items: Visual analogue scale (VAS), CgA in saliva,

IgA, salivary luminescence
- - 0m 13 30 43m 60 63
5mi 3mi in min min in min min
n n brea brea
k k

2mi 2mi 2mi

n Stress loading n Stress loading n
in inta (Kraepelin test) (Kraepelin
Saliva ke Saliva test) Saliva
sampling
Change in CgA with GABA-Coffee>
140
ミ ネ Mineral
ラルウォーター
130 water
GABA無 添 加GABA-
Non コーヒー
120 containing
GABA添 加コーヒー
GABA-
CgA変化率（％）

Fluctua 110 containing

tion
100
Rate of 90
CgA 80
70
(%)
60
0 10 20 30 40 50 60 70
飲料摂取後時間（分）

Time passage after test

substance intake (min)
 Salivary LuminescenceEntry
H2O slot record
3 kinds of
Light- peroxidases,
2 er

emitting thiocyanate ion,

and other few
materials
・ Antibacterialkinds.
oral cavity
action in the

・ Natural immune strength of

main body

•Responds to various
stresses Weak luminescence measurement device
微弱発光測定装置（浜松ホトニクス
(Hamamatsu photonics )
（株））
微弱発光量の計測グラフ
•Fluctuates according to Measurement graph of weak
1400 luminescence
slight emotional 1200 After stress
loading
changes 1000
(counts/ 100sec)

800
photon

600
Superior features to traditional 400
Before stress
ストレス負荷前
stress markers 200
0
loading
1 11 21 31 41 51 61 71 81 91 101 111121
time
 Change in stress level and luminescence –
emitting amount in
Kraepelin stress – loading test
250

200

150
（％）

100
Mineral
ミネラル ウォーター
water
Non GABA
50 ＧＡＢＡ無 添 加 coffee
コーヒー
GABA coffee
ＧＡＢＡ添 加 コーヒー
0
At静 時
安 30
３０分 後 60 Min.
６０分 後
rest Min.late later
drink r
Kraepelin test Kraepelin test
At rest 0min 30 min. 30 min.

Saliva sampling Saliva sampling Saliva sampling

 Pharma-GABA:
Clinical Summary
 Major neurotransmitter in brain
 Promotes relaxation
 Exerts anti-stress effects
 Improves sleep quality
 Exerts anti-caffeine effects
 Preliminary evidence indicates useful in:
– Stress, anxiety, nervousness, & sleep
disturbances
Dosage: 50 to 200 mg up to 6 times daily
 5-HTP: 5-
Hydroxytryptophan
Well researched direct precursor to

serotonin.
Advantages over L-tryptophan.
Absorption, CNS uptake, antioxidant aspect

5-HTP increases the level of serotonin.

5-HTP increases the level of endorphins.

5-HTP: A real serotonin solution.

 The Effects of Different
Levels of Serotonin
Optimal Level Low Level
Hopeful, optimistic Depressed
Calm Anxious
“Good-natured” Irritable
Patient Impatient
Reflective and thoughtful Impulsive
Loving and caring Abusive
Able to concentrate Short attention span
Creative, focused Blocked, scattered
Able to think things through “Flies off the handle”
Responsive Reactive
Does not overeat carbohydrates Craves carbohydrates
Sleeps well with good dream recall Insomnia\poor dream recall
 The Effects of Different
Levels of Beta-Endorphin
Optimal Level Low Level
High tolerance for painLow pain tolerance
Sensitive, sympathetic Tearful, reactive
High self-esteem Low self-esteem
Hopeful, optimistic, euphoric Depressed, hopeless
Takes personal responsibilityFeels like a victim
Solution-orientedProblem-oriented
No addiction to sweet foods Craves sweets
 Conditions Associated with
Low Serotonin Levels
Obesity
Insomnia
Carbohydrate
Narcolepsy
craving
Bulemia Sleep apnea

Depression Headaches

Anxiety PMS

Obsessive Fibromyalgia
compulsive Seizure
disorder disorders
Key Factors Linked to

Low Serotonin
Stress
Syndrome
Loss of sensitivity to insulin

Nutrient and cofactor deficiencies

Magnesium, B vitamins, SAM, biopterin, etc.

Hormonal imbalances
 Tryptophan Pathways
Tryptophan Kynurenine pathway

5-HTP

Serotonin 5-Hydroxyindoleaceatic acid

(5-HIAA)
N-acetyl-serotonin

Melatonin
Psychopathology 24:53-81, 1991
5-HTP vs. Fluvoxamine:
Percentage Changes in the HDS
Time 5-HTP (n34) Fluvoxamine (n29)
% decrease in HDS
After 2 weeks 23 18.9
After 4 weeks 46.2 46.1
After 6 weeks 60.7 56.1

After 6 weeks number of patients per category

less than 35% decrease 4 5
35-50% decrease 8 3
50-75% decrease 12 8
more than 75% decrease 10 13
 5-HTP vs. Antidepressant
Drugs: Comparison of Side Effects
Side Effect % of Patients Experiencing Side Effect
5-HTP Tricyclics SSRIs
Nausea 9% 15% 23%
Headache 5% 16% 20%
Nervousness 2.5% 11% 16%
Insomnia 2.5% 7% 17%
Anxiety 2.5% 9% 14%
Drowsiness 7% 23% 11%
Diarrhea 2.5% 4% 12%
Tremor 0% 18% 11%
Dry mouth 7% 64.5% 12%
Sweating 2.5% 15% 9%
Dizziness 5% 25.5% 7%
Constipation 5% 25% 5.5%
Vision Changes 0% 14.5% 4%
 5-HTP in Insomnia
 Increases both serotonin and
melatonin levels
 Enhances sleep quality
Reduces sleep latency and promotes
sleep maintainence
Increases REM sleep
Increases non-REM deep sleep stages 3
and 4
 Useful in sleep apnea, narcolepsy,
and other parasomnias
 5-HTP: Clinical
Guidelines
 Dosage:
Begin with 50 mg 3x/d for two weeks,
increase up to 200 mg 3x/d if necessary
Give 20 minutes before meals for weight
loss
In children: 4.5 to 5 mg per kg body
weight in divided dosages

 Side Effects:
Most common: Nausea, drowsiness
 L-theanine:
Clinical Summary
 Major amino acid in green tea
 Preliminary evidence indicates useful in:
– Anxiety, nervousness, & sleep disturbances
– ADD
Increases brain GABA and dopamine levels
Does not produce drowsiness
Dosage: 100 to 200 mg up to 6 times daily
 Suntheanine - Patented
Technology
•Suppression of Anxiety, Obesity, PMS, Menopause, and Sleep Disorders -
US Patent 6,589,566
•Composition for Improving Mental Concentration - WO 02089786
•Composition for Ameliorating ADD/ADHD - WO0210039
•Compositions for Regulating Desire for Smoking - US 20030003130
•Compositions for Ameliorating Blood Flow - JP2001316256
•Compositions for Promoting Sleep - WO 01/74352
•Composition for Suppressing Behavior Problems of Pets - US Patent
6,297,280
•Anxiety Inhibitory Composition - JP2001089365
•Composition for Pet Food Effective for Improving Palatability -
JP2001029022
•Theanine Containing Composition - JP2000247878, JP9012454
•Premenstrual Syndrome Depressant Composition - JP2000143508
•Anti-Obesity Composition - JP2000053568
•
 L-Theanine and
Glutamine

L-Theanine L-Glutamine

GABA**
 Classification of Brain
Waves
0.5 ~ 3Hz

Delta δ waves deep sleep

4 ~ 7Hz
Theta θ waves light sleep

8 ~ 13Hz
Alpha α waves awake, relaxed

14 ~

Beta β waves awake, excited

 Brain Wave Topography

Weak Front strong

Rear
 Topography Changes of Brain
Waves after Oral Administration
of Water
After 10 min 20 min 30 min 40 min 50 min 60 min

Theta waves
4 - 8 Hz

Alpha 1 waves
8 - 10 Hz

Alpha 2 waves
10 - 13 Hz
 Topography Changes of Brain Waves
after Oral Administration of L-
theanine
After 10 min 20 min 30 min 40 min 50 min 60 min

Theta waves
4 - 8 Hz

Alpha 1 waves
8 - 10 Hz

Alpha 2 waves
10 - 13 Hz
 Effect of L-theanine on the
Emission of Alpha Waves Based
on Anxiety
1.3
Relative ratio

1.2

1.1

1.0

0mg 50mg 200mg 0mg 50mg 200mg

Low anxiety group High anxiety group

Nippon Nogeikagaku kaishi, 72(2), 153-157, 1998

 Sleep Efficiency
100
p=0.047
99

98

97 96.6

96
%

95

94 93.8

93 n=22
92

91

90
プラセボ テアニン
Placebo Theanine
 L-Theanine, 5-HTP,
Melatonin Chewable
Tablet for Insomnia
Each chewable tablet contains:
L-Theanine 200 mg
5-HTP 25 mg
Melatonin 1.5 mg

Dosage: One or two tablets 30 to

45 minutes before bedtime