1. Stress Management: Phytotherapeutic Strategies for Adrenal Health Angela Hywood ND (Australia) B App Sc (Naturopathy); Dip Bot Med; Dip Hom; Dip NFM Member NHAA, ANTA, AHG

2. 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

3. 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 www.jbpub.com/samples/0763740411

4. 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 www.jbpub.com/samples/0763740411

5. normal resistance state alarm phase Phase 1 resistance phase Phase 2 exhaustion phase Phase 3 anabolic phase catabolic phase SELYE’S STRESS MODEL General Adaptation Syndrome www.brainconnection.com/topics/?main=fa/selye

6. 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

7. 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

8. Sources of Stress Psychological and Social Stressors  Performance stress (school, job, home)  Financial  Emotional worry  Relationship issues

9. Sources of Stress Biological  Viruses  Bacteria  Parasites Physiological Stressors  Nutritional deficiency  Biological aging  Illness (surgery)  Trauma  Toxicity

10. Adaptogens conserve adaptation energy  Eleuthero  Withania  Rhodiola  Codonopsis  Polygonum  Korean Ginseng  Tribulus Adaptogen vs Adrenal Tonics

11. General Tonics increase or release adaptation energy  Korean Ginseng  Astragalus Adrenal tonics support the adrenal cortex  Licorice  Rehmannia  Tribulus Adaptogen vs Adrenal Tonics

12. Allostasis refers to the process by which our bodies attempt to maintain homeostasis in response to environmental change and/or stressors 1 It links the brain which perceives a new or threatening situation, the endocrine system (HPA axis), and the immune system 1,2 Allostatic load refers to the cost of adaptation or the damage that an improperly functioning allostatic response causes or accumulates 1,2 1 McEwen BS. Metabolism 2003; 52(10)(suppl. 2): 10-16 2 Ray O. Am Psychol 2004; 59(1): 29-40 Allostasis and Allostatic Load

13. 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

14. Phase 1: Normal Adaptation and Resistance in Alarm phase both Cortisol and DHEA increase with stress usually asymptomatic SELYE’S STRESS MODEL General Adaptation Syndrome normal resistance state alarm phase Phase 1 resistance phase Phase 2 exhaustion phase Phase 3 anabolic phase catabolic phase

15. Phase 2: Resistance Phase (early stage of exhaustion) Cortisol increases but DHEA declines “stressed”, anxiety attacks, mood swings, small constricted pupils ANS in sympathetic dominance SELYE’S STRESS MODEL General Adaptation Syndrome normal resistance state alarm phase Phase 1 resistance phase Phase 2 exhaustion phase Phase 3 anabolic phase catabolic phase

16. normal resistance state alarm phase Phase 1 resistance phase Phase 2 exhaustion phase Phase 3 anabolic phase catabolic phase Phase 3: Exhaustion Phase (late stage of exhaustion) Both Cortisol and DHEA are low depression and exhaustion; large pupils ANS in parasympathetic dominance SELYE’S STRESS MODEL General Adaptation Syndrome

17. 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

18. 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

19. Sample of Cortisol Circadian Cycle Reference Ranges Patient Results Free Cortisol (nM) 8 am Noon 4 pmMidnight 30 25 20 15 10 5 0 Figure 1. Circadian Cortisol Profile

20. Adrenal Hormones Involved in the Stress Response Cortisol influences the activity of: Insulin Thyroid DHEA Testosterone Estrogen

21. Adrenal Hormones Involved in the Stress Response Cortisol is involved with: Blood glucose regulation Immune system response Bone turnover rate Mood and thought REM sleep Protein catabolism

22. Manufacture of Cortisol under Stress

23. Elevated cortisol is associated with: Anxiety Insulin resistance Obesity Osteoporosis Sex hormone imbalance Onset insomnia Accelerated aging Immune suppression Adrenal Hormones Involved in the Stress Response

24. Low cortisol is associated with: CFS Depression Anorexia nervosa PMS Menopause Fibromyalgia Impotence in men Infertility Maintenance insomnia

25. 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.

26. DHEA (Dehydroepiandrosterone) 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 Larsen P, et al. Williams Textbook of Endocrinology, 10th edition. Philadelphia: Saunders Publishers, December 2002.

27. DHEA (Dehydroepiandrosterone) 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) Larsen P, et al. Williams Textbook of Endocrinology, 10th edition. Philadelphia: Saunders Publishers, December 2002.

28. Decline in immunity Chronic fatigue Arthridites Insomnia Decreased libido Obesity Depression Osteoporosis Low DHEA-S is involved with: Adrenal Hormones Involved in the Stress Response

29. 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

30. 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

31. 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 root 1 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, prostaglandins 2,3 1 Miller SC. eCAM 2005; 2(3): 309-314 2 Christopher FL, Dussault I, Miller SC. Immunobiology 1991; 184: 37-52 3 Dussault I, Miller SC. Nat Immun 1993; 12: 66-78

32. 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 weeks 1 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

33. 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

34. Echinacea Reverses Immune 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 cells 1 1 Currier NL, Miller SC. Exp Gerontol 2000; 35: 627-639

35. 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 Reverses Immune Aging

36. 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 Beneficial if Taken Regularly

37. 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

38. “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 Echinacea is Beneficial if Taken Regularly

39. 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 Echinacea is Beneficial if Taken Regularly

40. 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)

41. 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.

42. 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

43. 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

44. Core Phytotherapy for Adrenal Health Adaptogens  Withania  Korean Ginseng  Tribulus Adrenal Tonics  Licorice

45. 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

46. 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

47. Mode of Action of Adaptogens 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

48. Mode of Action of Adaptogens 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.

49. 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

50. Stress Management Protocol Treatment 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

51. Licorice: Actions Adrenal tonic  Contraindicated in hypertension Anti-inflammatory Mucoprotective Demulcent Anti-ulcer (peptic) Expectorant Antitussive Mild laxative Dose:Licorice High Grade 1:1, 2-4 mL per day

52. Stress Management Protocol Treatment 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

53. 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

54. 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

55. 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)

56. Phase 2 Adrenal Stress Protocol 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 Approach Withania Complex tablets (2 to 4 per day) in the 2-4 pm energy slump time of the afternoon

57. Phase 2 Adrenal Stress Protocol ANS in Sympathetic Dominance Tonic Herbal Formula Licorice High Grade1:130 mL Echinacea Premium1:220 mL Zizyphus 1:220 mL Withania1:130 mL 100 mL Dose: 8 mL with water twice a day

58. Phase 3 Adrenal Stress Protocol 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 Support Echinacea Premium (2 tablets or 5 mL per day)

59. Phase 3 Adrenal Stress Protocol ANS in Parasympathetic Dominance Tonic Herbal Formula Grade Licorice High Grade1:120 mL St John’s Wort High Grade1:230 mL Tribulus2:150 mL 100 mL Dose: 8 mL with water twice a day

60. 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

61. 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

62. 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  Gravimetric40%  UV3% by Bulgarian method Raw herb results  Fruit0.5%  Aerial parts3.5%

63. 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.

64. 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)

65. 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

66. 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

67. Case Study Family History:  Breast cancer (mother)  Osteoporosis (mother, grandmother)  Osteoarthritis (mother, grandmother and grandfather)

68. 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

69. Adrenal Stress Index Test 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

70. Protocol Development Manage HPA Axis and support endogenous production of GH/DHEA  Tribulus Forte (2 tablets twice daily)

71. Protocol Development Select an adaptogen:  Withania 1:1 extract 5 mL daily in the evening Ideal for elevated cortisol

72. Protocol Development Select an adrenal tonic:  Rehmannia 1:2 extract 5 mL mid morning when cortisol is lowest Ideal for low DHEA-S and elevated cortisol

73. Protocol Development Supportive Herbal Formula (Sympathetic dominance basis of support) Californian Poppy 1:2 100 mLNervine Valerian 1:2 100 mLNervine Echinacea Premium 1:2 80 mLImmune support Gotu Kola 1:1 120 mLMS support Chaste Tree 1:2 100 mLPineal and Pituitary 500 mL Dose: 8 mL twice daily

74. 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

75. normal resistance state alarm phase Phase 1 resistance phase Phase 2 exhaustion phase Phase 3 anabolic phase catabolic phase Phase 1: Support (ie supporting normal or borderline adrenals) Simple approach with Withania Complex tablets Sympathetic Dominant 3 months recovery time SELYE’S STRESS MODEL General adaptation syndrome

76. normal resistance state alarm phase Phase 1 resistance phase Phase 2 exhaustion phase Phase 3 anabolic phase catabolic phase Sympathetic Dominant 6 months recovery time Phase 2: Withania 1:1 will bring elevated cortisol down to normal levels and to support DHEA. Support with Adrenal tonics such as Tribulus Forte tablets; Licorice High Grade 1:1. Note: In cases of hypertension use Tribulus instead of Licorice. SELYE’S STRESS MODEL General adaptation syndrome

77. normal resistance state alarm phase Phase 1 resistance phase Phase 2 exhaustion phase Phase 3 anabolic phase catabolic phase Phase 3: Licorice High Grade 1:1, Tribulus Forte tablets, Korean Ginseng. Note: In cases of hypertension use Tribulus instead of Licorice. 1 year recovery time SELYE’S STRESS MODEL General adaptation syndrome

78. 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