Stress Management: Phytotherapeutic Strategies for Adrenal Health Angela Hywood ND (Australia)

Stress Management: Phytotherapeutic Strategies

for Adrenal Health

Angela Hywood ND (Australia)B App Sc (Naturopathy); Dip Bot Med; Dip Hom; Dip NFMMember NHAA, ANTA, AHG

Hans Selye

• Adrenal research pioneer• Spent his lifetime in continuing research on

General Adaptation Syndrome (GAS) and wrote some 30 books and more than 1,500 articles on stress and related problems, including: Stress without Distress (1974) The Stress of Life (1956) Running out of GAS

• Selye formulated the General Adaptation Syndrome (GAS) as a non-specific response to stress

• This GAS enables you to increase your power of resistance to stressors and to adapt to environmental change

General Adaptation Syndrome

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• According to Hans Selye & W. Cannon (1935-6), stress is a state of threatened homeostasis the term was borrowed from physics

• A stressor is any agent or condition which threatens homeostasis

Stress & Adrenal Depletion

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normalresistance

state

alarm phase

Phase 1resistance phase

Phase 2exhaustion phase

Phase 3

anabolic phase

catabolic phase

SELYE’S STRESS MODELGeneral Adaptation

Syndrome

www.brainconnection.com/topics/?main=fa/selye

Adaptation Energy

• According to Selye there is a finite amount of “adaptation energy” which declines with increasing or continuous exposure to stressors

• One of the sequelae to this decrease is faulty adaptation and disease

Selye H. Br Med J 1950; 1(4667): 1383–1392

Sources of Stress

• Environmental Stress Weather (amount of sunlight,

temperature) Noise Pollution Radiation (gamma, ionizing, non-

ionizing)- cell phones, computers, electrical

equipment, power lines, air travel etc

Sources of Stress

• Psychological and Social Stressors Performance stress (school, job, home) Financial Emotional worry Relationship issues

Sources of Stress

• Biological Viruses Bacteria Parasites

• Physiological Stressors

Nutritional deficiency

Biological aging

Illness (surgery)

Trauma Toxicity

• Adaptogens conserve adaptation energy Eleuthero Withania Rhodiola Codonopsis Polygonum Korean Ginseng Tribulus

Adaptogen vs Adrenal Tonics

• General Tonics increase or release adaptation energy

Korean Ginseng Astragalus

• Adrenal tonics support the adrenal cortex Licorice Rehmannia Tribulus

Adaptogen vs Adrenal Tonics

• Allostasis refers to the process by which our bodies attempt to maintain homeostasis in response to environmental change and/or stressors1

• It links the brain which perceives a new or threatening situation, the endocrine system (HPA axis), and the immune system1,2

• Allostatic load refers to the cost of adaptation or the damage that an improperly functioning allostatic response causes or accumulates1,2

1 McEwen BS. Metabolism 2003; 52(10)(suppl. 2): 10-162 Ray O. Am Psychol 2004; 59(1): 29-40

Allostasis and Allostatic Load

• The primary mediators of allostasis are adrenal steroids (cortisol), catecholamines (epinephrine, norepinephrine) and dehydroepiandrosterone (DHEA)

• Each has short term protective adaptive actions (allostasis) and long term damaging effects (allostatic load)

McEwen BS, Seeman T, Ann NY. Acad Sci 1999; 896: 30-47

Allostasis and Allostatic Load

Phase 1Phase 1: Normal Adaptation and Resistance in Alarm phase: Normal Adaptation and Resistance in Alarm phase both Cortisol and DHEA increase with stressboth Cortisol and DHEA increase with stress

usually asymptomaticusually asymptomatic


Syndromenormalresistance

state

alarm phase



Phase 3

anabolic phase

catabolic phase

Phase 2Phase 2: Resistance Phase (early stage of exhaustion): Resistance Phase (early stage of exhaustion)Cortisol increases but DHEA declinesCortisol increases but DHEA declines

““stressed”, anxiety attacks, mood swings, small constricted pupilsstressed”, anxiety attacks, mood swings, small constricted pupilsANS in sympathetic dominanceANS in sympathetic dominance


Syndromenormalresistance

state

alarm phase



Phase 3

anabolic phase

catabolic phase

normalresistance

state

alarm phase



Phase 3

anabolic phase

catabolic phase

Phase 3Phase 3: Exhaustion Phase (late stage of exhaustion): Exhaustion Phase (late stage of exhaustion)Both Cortisol and DHEA are lowBoth Cortisol and DHEA are low

depression and exhaustion; large pupilsdepression and exhaustion; large pupilsANS in parasympathetic dominanceANS in parasympathetic dominance


Syndrome

Measurement of Cortisol Levels

• The body's level of cortisol in the bloodstream displays what is known as a diurnal variation

normal concentrations of cortisol vary throughout a 24-hour period

• Cortisol levels in normal individuals are highest in the early morning at around 6-8 am and are lowest around midnight

Michaud K, Matheson K, Kelly O, Anisman H. Stress 2008; 11(3):177-97

Measurement of Cortisol Levels

• In addition to early morning, cortisol levels may be somewhat higher after meals

• While the most common test is measurement of the cortisol level in the blood, some doctors measure cortisol through a saliva sample, as salivary cortisol levels have been shown to be an index of blood cortisol levels

Michaud K, Matheson K, Kelly O, Anisman H. Stress 2008; 11(3):177-97

Sample of Cortisol Circadian Cycle

Reference Ranges

Patient Results

Fre

e C

ort

iso

l (n

M)

8 am Noon 4 pm Midnight

30

25

20

15

10

5

0

Figure 1. Circadian Cortisol Profile

Adrenal Hormones Involved in the Stress

ResponseCortisol influences the activity of:• Insulin• Thyroid • DHEA• Testosterone• Estrogen


ResponseCortisol is involved with:• Blood glucose regulation• Immune system response• Bone turnover rate• Mood and thought • REM sleep• Protein catabolism

Manufacture of Cortisol under Stress

Elevated cortisol is associated with:• Anxiety• Insulin resistance• Obesity• Osteoporosis• Sex hormone imbalance• Onset insomnia• Accelerated aging• Immune suppression


Response


ResponseLow cortisol is associated with:• CFS• Depression• Anorexia nervosa• PMS• Menopause• Fibromyalgia• Impotence in men• Infertility• Maintenance insomnia

DHEA (Dehydroepiandrosterone)

• Functions as an androgen (a male hormone) with anabolic activity

• Is a precursor to testosterone in men and is a precursor that is converted to testosterone in men and estrogen in women

• Reverses immune suppression caused by excess cortisol levels

Larsen P, et al. Williams Textbook of Endocrinology, 10th edition. Philadelphia: Saunders Publishers, December 2002.


• Stimulates bone deposition and remodeling to prevent osteoporosis

• Improves cardiovascular status by lowering total cholesterol and LDL levels, thereby lessening incidences of heart attack

• Increases muscle mass. Decreases percentage of body fat

• Involved in the thyroid gland's conversion of the less active T4 to the more active T3



• DHEA negates many of the unfavorable effects of excess cortisol, creating subsequent improvement in energy/vitality, sleep, premenstrual symptoms, and mental clarity

• Accelerates recovery from any kind of acute stress (eg insufficient sleep, excessive exercise, mental strain, etc)


• Decline in immunity• Chronic fatigue• Arthridites• Insomnia• Decreased libido• Obesity• Depression• Osteoporosis

Low DHEA-S is involved with:


Response

Adrenal Depletion

• In terms of herbal actions required for a treatment protocol for adrenal depletion: Adrenal tonic or restorative herbs Adaptogens Tonics (general or whole body tonics) Nervine tonics Immune facilitators

Prolonged Stress

• The systemic effects of stress include: Increased levels of stress hormones such

as cortisol Decline in certain aspects of immune

system function such as:- Natural killer cell cytotoxicity- Secretory-IgA levels- Disruption of gastrointestinal microflora

balance

Echinacea: A Miracle Herb?• In an extraordinarily entitled paper: “Echinacea: a

Miracle Herb against Aging and Cancer?”, Dr Sandra Miller has recently reviewed her research on Echinacea, specifically Echinacea purpurea root1

• Dr Miller’s interest in Echinacea was triggered by her team’s research on the drug indomethacin, which is a COX inhibitor that reduces the suppressors of natural killer (NK) cells, prostaglandins2,3

1 Miller SC. eCAM 2005; 2(3): 309-3142 Christopher FL, Dussault I, Miller SC. Immunobiology 1991; 184: 37-523 Dussault I, Miller SC. Nat Immun 1993; 12: 66-78

Echinacea Boosts NK Cells

• In healthy young adult mice, oral doses of Echinacea purpurea root (0.45 mg per 25 g body weight, similar to human dose rates) stimulated NK cell production by bone marrow in the first 7 days which resulted in significantly higher levels (around 25% more) of NK cells in the spleen by 2 weeks1

• In addition, the ‘helper’ or accessory cells for NK cells, the monocytes, were also increased by 25%

1 Sun LZ-Y, Currier NL, Miller SC. J Altern Complement Med 1999; 5: 437-446

Echinacea Boosts NK Cells

• The Echinacea treatment influenced no other white blood cell counts

• Polysaccharides, even by injection, were found to be not responsible for this effect

• Dr Miller feels that alkylamides are largely responsible for the effect (personal communication)

Currier NL, Lejtenyi D, Miller SC. Phytomedicine 2003; 10: 145-153

Echinacea ReversesImmune Aging

• NK cells decline in number and function with age and this is thought to be one factor behind the increase of various cancers with age

• Experiments conducted in healthy, elderly mice found that 2 weeks of oral doses of Echinacea returned NK cell numbers in bone marrow and spleen to the levels of young adults and also resurrected the functional capacity (target cell binding, lysis) of these cells1

1 Currier NL, Miller SC. Exp Gerontol 2000; 35: 627-639

• On this result Dr Miller writes:

“These observations appear to apply uniquely to this herb since we could never rejuvenate the NK cell-mediated component of the immune system in elderly mice by any of the other typical NK cell enhancers….”

Miller SC. eCAM 2005; 2(3): 309-314

Echinacea ReversesImmune Aging

• One of the persistent controversies about Echinacea is whether it is safe to be taken consistently for long periods of time. According to Miller’s findings, the answer is definitely in the affirmative

• Mice were fed Echinacea purpurea root from 7 weeks of age to 13 months at the dose previously described.1 Long-term use of Echinacea was not only not detrimental, but distinctly beneficial

1 Brousseau M, Miller SC. Biogerontology 2005; 6: 157-163

Echinacea is Beneficialif Taken Regularly


• By 13 months of age 46% of the control mice fed the standard chow were still alive compared to 74% of those consuming Echinacea

• As might be expected from previous experiments, the NK cell levels in the Echinacea-fed mice were considerably elevated compared to controls

Miller SC. eCAM 2005; 2(3): 309-314

“Given that the key immune cells acting as the first line of defence against developing neoplasms in mice and humans are NK cells, it is not difficult to conclude that sustained enhancement of NK cells alone, throughout life, could readily account for the reduced frequency in deaths with advancing age.

Miller SC. eCAM 2005; 2(3): 309-314


Spontaneous neoplasms, clinically undetectable, are well known to increase with advancing age in humans and mice.Thus, the logical corollary from this study indicates that chronic daily intake of Echinacea, is clearly not detrimental to the immune system, but rather prophylactic.”

Miller SC. eCAM 2005; 2(3): 309-314


Clinical Tests To Evaluate Physiological Stress

• The most accurate objective method to assess adrenal status is via Adrenal Stress Index (ASI) Salivary Hormone Test Metametrix Labs (www.metametrix.com) Diagnostechs Labs

(www.diagnostechs.com)

Primary Evaluation for Adrenal Fatigue

Ragland’s Postural Hypotension Test • This test is performed by taking the blood pressure

while the patient is lying down, and repeating immediately after the patient stands up

• A systolic increase of 5 to 10 mm upon standing is a normal response to this sudden change in gravity

• A systolic blood pressure that fails to rise (or falls) when standing, adrenal fatigue and a lack of adrenals ability to adapt to gravitational changes (physical stressor)

Weatherby D, Ferguson S. In-Office Lab Testing - Functional Terrain Analysis. 2005.

Primary Evaluation for Adrenal Fatigue

• Pupil Dilation Test Equipment required: flashlight and a mirror Shine the flashlight into the pupil of one

eye It should contract if adrenals are healthy

and adapting to light stressor If after 30 seconds, it stays the same or,

even worse, dilates, this is an indicator of adrenal fatigue

• Pain when pressing on adrenal glands (located over kidneys) Palpation or symptom of chronic lower back

pain in the absences of structural issues

Natural Medicine for Adrenal Health

• These include: Adaptogenic herbs

such as Eleuthero and Withania

Adrenal Tonic herbs such as Licorice and Rehmannia

Vitamin C Vitamin B1 Vitamin B6

Vitamin B5 (pantethine)

Vitamin B12 (methylcobalamin)

Tyrosine Lipoic acid (naturally

found in liver) Phosphatidylserine Plant sterols, such as

those found in Tribulus and Korean Ginseng

Rogero MM, Mendes RR, Tirapegui J. Arq Bras Endocrinol Metabol 2005 Jun; 49(3):359-68 Epub 2006 Mar 16

Core Phytotherapy for Adrenal Health

Adaptogens Withania Korean Ginseng Tribulus

Adrenal Tonics Licorice

Adrenal Tonics

• Nourish the adrenal glands• Allow for improved regulation of cortisol and

DHEA output• Release stored adaptation energy• Reduce side effects of corticosteroid drug

use• Cortisol sparing action in cases of Phase 3

exhaustion of adrenals

Mode of Action of Adaptogens

General Effects• Fine-tune the stress response mechanism so

that Phase 1 of GAS is more efficient• Response is stronger and faster and feedback

control is more effective so the response is shut off faster

• Have a sparing effect in Phase 2, so that Phase 3 is delayed

• So they are biphasic, can increase or decrease stress response

Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Churchill Livingstone, Edinburgh, 2000.

Gaffney B, et al. Medical Hypotheses 2001; 56(5): 567-572


Specific Effects• Positive effects on biosynthesis of RNA and proteins• Positive effects on carbohydrate metabolism, eg

increased formation of glucose-6-phosphate• Reduction of catecholamine depletion by inhibition of

catecholamine-O-methyl transferase (COMT) – especially in CNS (mainly Eleuthero)

• Inhibition of breakdown of corticosteroids via inhibition of 11-beta hydroxysteroid dehydrogenase in CNS

Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Churchill Livingstone, Edinburgh, 2000

Gaffney B, et al. Medical Hypotheses 2001; 56(5): 567-572


Adaptogens and Immunity• Increased secretion of glucocorticoids in response to

injury or infection is to prevent defence mechanisms from overreacting

• Acute and chronic stress can result in immune suppression (well-known in athletes), probably by this mechanism

• By their positive effects in Phase 2, adaptogens will counter chronic immune depletion in stressed individuals

Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Churchill Livingstone, Edinburgh, 2000.

Actions of Adaptogens

• Improved adaptation to stress• Promote regeneration• Increased concentration• Fewer mental errors• May sensitize corticosteroid feedback on the

HPA axis making the stress response more efficient

• Increase glucocorticoid action

Stress Management ProtocolTreatment Strategy• Support the adrenal gland function with

adrenal restorative (adrenal tonics) herbs such as: Licorice High Grade 1:1

- 2-4 mL per day- Phase 2 or 3 adrenal stress or exhaustion- Contraindicated in hypertension- If hypertensive patient, use Tribulus Forte

(2 tablets twice daily) as alternative

Licorice: Actions• Adrenal tonic

Contraindicated in hypertension• Anti-inflammatory• Mucoprotective• Demulcent• Anti-ulcer (peptic)• Expectorant• Antitussive• Mild laxativeDose: Licorice High Grade 1:1, 2-4 mL per day

Stress Management ProtocolTreatment Strategy• Decrease the detrimental effects of stress on

the adrenal glands with adaptogens such as: Withania 1:1 (5-10 mL per day) for Phase 2

adrenal stress Tribulus Forte (2 tablets twice daily) for

Phase 3 adrenal exhaustion

Withania: Actions

• Adrenal adaptogen Particularly if high cortisol levels

• Mild sedative or relaxant Promotes a feeling of calmness and more

sustained energy Useful for insomnia

Withania: Actions

• Anti-inflammatory• Immune modulating

Promotes the production of white blood cells Enhances immune function

• Antianemic Promotes the production of red blood cells

• Promotes growth and appetite in children and adults

Dose: Withania 1:1 extract, 5-10 mL per day

Phase 2 Adrenal Stress Protocol

ANS in Sympathetic Dominance• Adrenal Tonic

Licorice High Grade 1:1 (2 mL per day) or Tribulus Forte (2 tablets twice daily) if patient hypertensive

• Adaptogen Withania 1:1 extract (5-10 mL per day) or

Tribulus Forte (4 tablets per day) or liquid 2:1 (10 mL per day)


ANS in Sympathetic Dominance• Nervous System Support

Valerian Complex tablets (3 to 4 per day)Zizyphus 1:2 (5 mL per day)Hawthorn 1:2 (5 mL per day, if cardiac

symptoms)• Simplified ApproachWithania Complex tablets (2 to 4 per day) in the

2-4 pm energy slump time of the afternoon


ANS in Sympathetic Dominance

Tonic Herbal FormulaLicorice High Grade 1:1 30 mLEchinacea Premium 1:2 20 mLZizyphus 1:2 20 mLWithania 1:1 30 mL

100 mLDose: 8 mL with water twice a day


ANS in Parasympathetic Dominance• Adrenal Tonic

Licorice High Grade 1:1 (4 mL per day)• Adaptogen Tribulus Forte (2 tablets twice daily)• Nervous System Support Nevaton tablets (4 per day)• Immune SupportEchinacea Premium (2 tablets or 5 mL per day)


ANS in Parasympathetic Dominance

Tonic Herbal Formula GradeLicorice High Grade 1:1 20 mLSt John’s Wort High Grade 1:2 30 mLTribulus 2:1 50 mL

100 mLDose: 8 mL with water twice a day

Tribulus

• In recent years, Tribulus has gained a reputation as an optimal herb to support both endogenous GH and DHEA levels for the age of the individual

• This is a native herb to many parts of the world but it is the Bulgarian Tribulus which has been extensively researched

• The active components of Tribulus herb are steroidal saponins, mainly the furostanol saponins, especially protodioscin

Tribulus

• Clinically documented benefits include: Growth hormone regulation via HP axis Intensification of protein synthesis (anabolic) Male and female infertility Menopause Andropause Impotence Erectile dysfunction Libido enhancing

Tribulus: Quality Issues

• Bulgarian clinical trials are based on a leaf extract containing 40% furostanol saponins by UV-Vis measurement

• Chinese and Indian sources are of a different Tribulus chemotype and typically use the fruit, analyzed at 40% by gravimetric methods Gravimetric 40% UV 3% by Bulgarian method

• Raw herb results Fruit 0.5% Aerial parts 3.5%

Stress Management Protocol

Simplified Treatment and Maintenance Strategy

• Withania Complex tablets (3 to 4 per day) Ideal for either parasympathetic or

sympathetic dominance due to adrenal stress

Contains Licorice, hence contraindicated in hypertension if used long term. Short term use is appropriate.

Case Study

Case History: • Female patient aged 46 presents with primary

complaints: Onset insomnia for the past 12 years with

night sweats. She had tried pharmaceutical medications in the past to no avail (temazepam and hormone replacement therapy)

She found the insomnia was worse after long term use of temazepam (rebound insomnia)

Case Study• Secondary complaints:

Hot flashes with perspiration: recent female hormonal pathology tests had revealed slightly low estrogen with normal progesterone. Thyroid panel normal (TSH, Free and bound T4 and T3 all within normal range)

Anxiety syndrome: not previously medicated as was resistance to the use of anti-anxiolytic or anti-depressant medications. Highly emotional, teary and irritable

Fatigue, worse mid-morning to midday

Case Study• Secondary complaints continued…

Very poor libido with subsequent relationship stress

Osteopenia (past 18 months), but currently taking calcium hydroxyapetite prescribed by primary medical doctor

Recurrent sinus infections. Three infections in a 8 month period with subsequent antibiotic and antifungal therapy

Case Study

• Family History: Breast cancer (mother) Osteoporosis (mother, grandmother) Osteoarthritis (mother, grandmother and

grandfather)

Case Study

• Lifestyle Factors: Exercise twice weekly (walking) Had gained 18 lb over the past 2 years

and was trying to reduce weight with a low carbohydrate diet but notes difficulty due to intense sugar and caffeine cravings

In an unhappy relationship, has 2 young children

Works a part-time high stress job

Adrenal Stress IndexTest Results

• Elevated afternoon cortisol often associated with poor glucose counter

regulation process• Low DHEA-S indicated anabolic enhancement

is necessary low DHEA-S is precursor issue to low

estrogen and testosterone• DHEA-S: cortisol relationship:

maladaption phase 2

Protocol Development

• Manage HPA Axis and support endogenous production of GH/DHEA Tribulus Forte (2 tablets twice daily)


• Select an adaptogen: Withania 1:1 extract

•5 mL daily in the evening•Ideal for elevated cortisol


• Select an adrenal tonic: Rehmannia 1:2 extract

•5 mL mid morning when cortisol is lowest

•Ideal for low DHEA-S and elevated cortisol

Protocol Development• Supportive Herbal Formula

(Sympathetic dominance basis of support)

Californian Poppy 1:2 100 mL NervineValerian 1:2 100 mL NervineEchinacea Premium 1:2 80 mL Immune supportGotu Kola 1:1 120 mL MS supportChaste Tree 1:2 100 mL Pineal and

Pituitary 500 mL

Dose: 8 mL twice daily

Results

• She was re-evaluated after 16 weeks on treatment with Salivary Adrenal Stress Index testing and her results showed normal adaptation to stress Insomnia was substantially improved, such

that she was achieving 7 hours of continual sleep per night and waking feeling refreshed

Libido had improved and menopausal symptoms had subsided

Energy remarkably improved - felt more “reserve” of energy rather than feeling anxious or fatigued

normalresistancestate

alarm phase



Phase 3

anabolic phase

catabolic phase

Phase 1:Phase 1: Support (ie supporting normal or borderline adrenals) Support (ie supporting normal or borderline adrenals)Simple approach with Withania Complex tabletsSimple approach with Withania Complex tablets

Sympathetic Dominant

3 months recovery time

SELYE’S STRESS MODELGeneral adaptation

syndrome


alarm phase



Phase 3

anabolic phase

catabolic phase

Sympathetic Dominant

6 months recovery time

Phase 2Phase 2:: Withania 1:1 will bring elevated cortisol down to normal Withania 1:1 will bring elevated cortisol down to normal levels and to support DHEA. Support with Adrenal tonics such as levels and to support DHEA. Support with Adrenal tonics such as Tribulus Forte tablets; Licorice High Grade 1:1.Tribulus Forte tablets; Licorice High Grade 1:1. Note: In cases of Note: In cases of

hypertension use Tribulus instead of Licorice.hypertension use Tribulus instead of Licorice.


syndrome


alarm phasePhase 1

resistance phase


Phase 3

anabolic phase

catabolic phase

Phase 3Phase 3: : Licorice High Grade 1:1, Tribulus Forte tablets, Korean Licorice High Grade 1:1, Tribulus Forte tablets, Korean Ginseng. Ginseng. Note: In cases of hypertension use Tribulus instead of Note: In cases of hypertension use Tribulus instead of

Licorice.Licorice.

1 year recovery time


syndrome

Acknowledgements

I would like to gratefully thank my colleagues Associate Professor Kerry Bone

Lee Carroll Curt Hamilton

for contributing to the preparation of information delivered in this presentation

Stress Management: Phytotherapeutic Strategies for Adrenal Health Angela Hywood ND (Australia)

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