stress, fatigue and the adrenals tom archie, md tom archie, md st lukes wood river family medicine...

Stress, Fatigue Stress, Fatigue and and

The AdrenalsThe Adrenals

Tom Archie, MDTom Archie, MD

St Luke’s Wood River St Luke’s Wood River Family MedicineFamily Medicine

www.drtomsalchemy.com

When My Patients Visualize Stress…When My Patients Visualize Stress…

When I Visualize StressWhen I Visualize Stress

Outline of this PresentationOutline of this Presentation

Differential Diagnosis of FatigueDifferential Diagnosis of Fatigue Hypothalamic– Pituitary – Adrenal AxisHypothalamic– Pituitary – Adrenal Axis

Physiology of Chronic StressPhysiology of Chronic Stress Chinese MedicineChinese Medicine Relaxation TechniquesRelaxation Techniques Four CasesFour Cases SupplementsSupplements SummarySummary

Depression, anxiety, anemia, thyroid Depression, anxiety, anemia, thyroid disorder, insomnia, infection, sleep apnea, disorder, insomnia, infection, sleep apnea, alcohol overuse, mitochondrial alcohol overuse, mitochondrial dysfunction, heart failure, menopause, dysfunction, heart failure, menopause, pregnancy, domestic or workplace abuse, pregnancy, domestic or workplace abuse, celiac, irritable bowel syndrome, celiac, irritable bowel syndrome, inflammatory bowel disease, medications, inflammatory bowel disease, medications, autoimmune disease, hypogonadism, B12 autoimmune disease, hypogonadism, B12 deficiency, malnutrition, electrolyte deficiency, malnutrition, electrolyte abnormalityabnormality

Fatigue Differential DiagnosisFatigue Differential Diagnosis

Tests that can Help Narrow the Tests that can Help Narrow the Differential Diagnosis ListDifferential Diagnosis List

Complete blood countComplete blood count Electrolytes, liver enzymes, urinalysisElectrolytes, liver enzymes, urinalysis Thyroid assessment*Thyroid assessment* Serum or salivary cortisol, DHEA-Sulfate, Serum or salivary cortisol, DHEA-Sulfate,

17-OH progesterone17-OH progesterone QuestionnairesQuestionnaires

Beck’s Depression IndexBeck’s Depression Index Metagenics Stress IdentiT ProtocolMetagenics Stress IdentiT Protocol Medical Symptoms QuestionnaireMedical Symptoms Questionnaire

If all you have is a HammerIf all you have is a HammerEverything looks like a NailEverything looks like a Nail

- Look Before You Leap -- Look Before You Leap -Don’t jump from symptom of Fatigue to Don’t jump from symptom of Fatigue to

ThyroidThyroidAdrenalAdrenalCandidaCandida

DepressionDepressionCancerCancer

Without Considering and Evaluating ThoroughlyWithout Considering and Evaluating Thoroughly

Chronic Fatigue SyndromeChronic Fatigue Syndrome Four or moreFour or more of the following symptoms that persist of the following symptoms that persist

or recur during or recur during 6 or more consecutive months6 or more consecutive months of of illness and that do not predate the fatigue:illness and that do not predate the fatigue:

Impaired short-term Impaired short-term memorymemory or or concentrationconcentration Sore throatSore throat Tender Tender lymph nodeslymph nodes MuscleMuscle pain pain MultiMultijoint painjoint pain without swelling or redness without swelling or redness HeadachesHeadaches of a new type, pattern, or severity of a new type, pattern, or severity UnrefreshingUnrefreshing and/or interrupted and/or interrupted sleepsleep Postexertion malaisePostexertion malaise lasting more than 24 hours lasting more than 24 hours

Exclusion criteria:Exclusion criteria: Active, unresolved or suspected disease that is likely to cause Active, unresolved or suspected disease that is likely to cause

fatiguefatigue Psychotic, melancholic, or bipolar depression (but not Psychotic, melancholic, or bipolar depression (but not

uncomplicated major depression)uncomplicated major depression) Psychotic disorders, Dementia, Anorexia or bulimia nervosaPsychotic disorders, Dementia, Anorexia or bulimia nervosa Alcohol or other substance misuseAlcohol or other substance misuse Severe obesitySevere obesity

Major DepressionMajor Depression Five or moreFive or more of the following symptoms during the same 2- of the following symptoms during the same 2-

week period and week period and one of the symptoms is eitherone of the symptoms is either (1) (1) depressed depressed moodmood or (2) or (2) loss of interest or pleasureloss of interest or pleasure..

Depressed moodDepressed mood (sad, empty, irritable or tearful most of most days (sad, empty, irritable or tearful most of most days Loss of interestLoss of interest or pleasure in most activities on most of most or pleasure in most activities on most of most

daysdays Change in Change in WeightWeight of >5% in a month or change in appetite of >5% in a month or change in appetite InsomniaInsomnia or or hypersomniahypersomnia nearly every day nearly every day Psychomotor agitation or retardation nearly every day (others Psychomotor agitation or retardation nearly every day (others

observeobserve restlessness restlessness or or slowing downslowing down)) FatigueFatigue or loss of energy nearly every day or loss of energy nearly every day Feelings ofFeelings of worthlessness worthlessness or inappropriate or inappropriate guiltguilt most days most days Difficulty Difficulty thinking/concentratingthinking/concentrating, or indecisiveness most days, or indecisiveness most days Recurrent Recurrent thoughts of deaththoughts of death or of suicide without specific plan or of suicide without specific plan

Clinically significant distress or impairment in social, Clinically significant distress or impairment in social, occupational, or other functionoccupational, or other function

Not due to the direct physiological effects of a substance Not due to the direct physiological effects of a substance abuse or medical condition abuse or medical condition

FibromyalgiaFibromyalgia Widespread Widespread body painbody pain present for present for at least 3 monthsat least 3 months

Both sides of the bodyBoth sides of the body Above and below the waistAbove and below the waist (low back considered below waist) (low back considered below waist) Includes axial skeletal pain (Includes axial skeletal pain (cervical spine, anterior chest, cervical spine, anterior chest,

thoracic spine or low back painthoracic spine or low back pain)) Strongly tender Strongly tender 11 of 18 tender points11 of 18 tender points (9 bilateral) (9 bilateral)

Occiput - suboccipital muscle insertions Occiput - suboccipital muscle insertions Low cervical - anterior aspects intertransverse spaces C5/7Low cervical - anterior aspects intertransverse spaces C5/7 Trapezius - midpoint of the upper borderTrapezius - midpoint of the upper border Supraspinatus – origins near the medial border of scapulaSupraspinatus – origins near the medial border of scapula Second rib - upper lateral to the second costochondral junctionSecond rib - upper lateral to the second costochondral junction Lateral epicondyle - 2 cm distal to the epicondyleLateral epicondyle - 2 cm distal to the epicondyle Gluteal - outer quadrants of buttocks in anterior fold of muscleGluteal - outer quadrants of buttocks in anterior fold of muscle Greater trochanter - posterior to the trochanteric prominenceGreater trochanter - posterior to the trochanteric prominence Knee - medial fat pad proximal to the joint lineKnee - medial fat pad proximal to the joint line

AcupunctureAcupuncture: : GB20,BL10,GB21,SI13,KI27,LI10,BL53,GB30,LR8GB20,BL10,GB21,SI13,KI27,LI10,BL53,GB30,LR8

Mayo Clinic on “Adrenal Fatigue”Mayo Clinic on “Adrenal Fatigue”www.mayoclinic.comwww.mayoclinic.com May 2010May 2010

“ “Proponents of the adrenal fatigue diagnosis claim this is Proponents of the adrenal fatigue diagnosis claim this is a mild a mild form of adrenal insufficiency caused by chronic stressform of adrenal insufficiency caused by chronic stress.. The The unproven theory behind adrenal fatigue is that your adrenal glands unproven theory behind adrenal fatigue is that your adrenal glands are unable to keep pace with the demands of perpetual fight-or-flight are unable to keep pace with the demands of perpetual fight-or-flight arousal. As a result, they can't produce quite enough of the arousal. As a result, they can't produce quite enough of the hormones you need to feel good. Existing blood tests, according to hormones you need to feel good. Existing blood tests, according to this theory, aren't sensitive enough to detect such a small decline in this theory, aren't sensitive enough to detect such a small decline in adrenal function — but your body is.adrenal function — but your body is.

It‘s frustrating to have persistent symptoms your doctor can't readily It‘s frustrating to have persistent symptoms your doctor can't readily

explain. But accepting a explain. But accepting a medically unrecognized diagnosismedically unrecognized diagnosis from from an unqualified practitioner could be worse. Unproven remedies for an unqualified practitioner could be worse. Unproven remedies for so-called adrenal fatigue may leave you feeling sicker, while the real so-called adrenal fatigue may leave you feeling sicker, while the real cause — such as depression or fibromyalgia — continues to take its cause — such as depression or fibromyalgia — continues to take its toll.” toll.”

Lacking in curiosity – Excessive in sarcasmLacking in curiosity – Excessive in sarcasm

Adrenal FatigueAdrenal Fatigue

It’s not a DiagnosisIt’s not a Diagnosis--

It’s a FunctionIt’s a Function

Functional Medicine MatrixFunctional Medicine Matrixwww.www.functionalfunctionalmedicine.orgmedicine.org

PerspectivePerspective

““Adrenal Fatigue” is not a standard medical Adrenal Fatigue” is not a standard medical diagnosisdiagnosis Therefore often dismissed by doctorsTherefore often dismissed by doctors Closest is “Adrenal Insufficiency” which is of much Closest is “Adrenal Insufficiency” which is of much

greater pathology and less commongreater pathology and less common• InheritedInherited deficiency of enzyme needed to make adrenal deficiency of enzyme needed to make adrenal

hormoneshormones

““Adrenal Fatigue” is a Adrenal Fatigue” is a real and common real and common phenomenon,phenomenon, but the term is often misused to but the term is often misused to encourage purchase of supplements encourage purchase of supplements instead of instead of lifestyle changeslifestyle changes..

PerspectivePerspective

““Adrenal Fatigue” describes the same Adrenal Fatigue” describes the same process known as “chronic stress” process known as “chronic stress” Elevated cortisol in response to stressElevated cortisol in response to stress Can lead to depression Can lead to depression

• Depression, Chronic Fatigue, and Fibromyalgia Depression, Chronic Fatigue, and Fibromyalgia have a common root = prolonged elevated cortisol have a common root = prolonged elevated cortisol due to chronic stressdue to chronic stress

Term “Adrenal Fatigue” coined by James Term “Adrenal Fatigue” coined by James Wilson, ND in 1990sWilson, ND in 1990s

PerceivedPerceived Stress Stress

OriginOrigin Physical, metabolic, psychological, emotionalPhysical, metabolic, psychological, emotional

TimingTiming Acute and short livedAcute and short lived

versusversus Chronic, persisting, and unrelentingChronic, persisting, and unrelenting

Section that follows credited to excellent chapter by Michael Lumpkin, PhDSection that follows credited to excellent chapter by Michael Lumpkin, PhD Lumpkin M. The Hypothalamic Pituitary Adrenal Axis. Textbook of Functional Lumpkin M. The Hypothalamic Pituitary Adrenal Axis. Textbook of Functional

Medicine. Ed. Jones D. Institute for Functional Medicine. 2005 Medicine. Ed. Jones D. Institute for Functional Medicine. 2005

StressorsStressors(Extensive research citations exist for the stressors listed below.)(Extensive research citations exist for the stressors listed below.)

Sleep deprivationSleep deprivation Financial stressFinancial stress PovertyPoverty Conflict (interpersonal, business)Conflict (interpersonal, business) Persecution (domestic violence, incarceration)Persecution (domestic violence, incarceration) DeathDeath DivorceDivorce Moving/RelocatingMoving/Relocating Attachment to Emotional Responses to EventsAttachment to Emotional Responses to Events Chronic PainChronic Pain Chronic IllnessChronic Illness

Hypothalamic Pituitary Adrenal AxisHypothalamic Pituitary Adrenal Axis

Cerebral Cortex

Hypothalamus

Pituitary

Adrenal sits on Kidney

Stress Response - HypothalamusStress Response - Hypothalamus

Endocrine System’sEndocrine System’s Command Center Command Center Monitors neuronal, hormonal, metabolic and Monitors neuronal, hormonal, metabolic and

immune signals within the bodyimmune signals within the body

compares them withcompares them with Signals from receptors for temperature, pain, Signals from receptors for temperature, pain,

pressure, electrolytespressure, electrolytes blends this information withblends this information with

Higher cortical brain’s state of mindHigher cortical brain’s state of mind• Fear, depression, agitation, anger, humor, Fear, depression, agitation, anger, humor,

contentmentcontentment

HypothalamusHypothalamus

Produces “master” hormones called Produces “master” hormones called Releasing Releasing HormonesHormones

Communicates to Pituitary GlandCommunicates to Pituitary Gland Corticotropin Releasing Hormone –Corticotropin Releasing Hormone – “ “CRH”CRH” (Adrenal) (Adrenal) Thyrotropin Releasing Hormone (Thyroid)Thyrotropin Releasing Hormone (Thyroid) Prolactin Releasing Hormone (Breast)Prolactin Releasing Hormone (Breast) Gonadotropin RH Gonadotropin RH

• LH and FSH - Testes, OvaryLH and FSH - Testes, Ovary• Growth hormone – skeletal/muscle growth, liver effect on Growth hormone – skeletal/muscle growth, liver effect on

sugar levelssugar levels

Releasing HormonesReleasing Hormones

Messages to Pituitary gland (Messages to Pituitary gland (intermediary intermediary for the other endocrine organsfor the other endocrine organs)) Stress response, reproduction, metabolism Stress response, reproduction, metabolism

(including thyroid), growth regulation, (including thyroid), growth regulation, lactation, balance of water/electrolyteslactation, balance of water/electrolytes

Regulates feeding, appetite, drinking, sex Regulates feeding, appetite, drinking, sex behaviors, emotions, hormonal rhythmsbehaviors, emotions, hormonal rhythms

Event Data Event Data mixes withmixes withEmotional ResponseEmotional Response

Cortex – higher brainCortex – higher brain Observes factual data from eventsObserves factual data from events Sends this via neurons to hippocampus & amygdalaSends this via neurons to hippocampus & amygdala

HippocampusHippocampus• Learning and memory transferred to long term memoryLearning and memory transferred to long term memory

AmygdalaAmygdala• Emotional responses are Emotional responses are ATTACHEDATTACHED to factual info to factual info

The Root of Suffering is the Attachment to EmotionsThe Root of Suffering is the Attachment to EmotionsWe often confuse our emotional response to an eventWe often confuse our emotional response to an event

with the data about the actual event with the data about the actual event And And

We hold tightly to our attachment to our emotionsWe hold tightly to our attachment to our emotionsProblem is not the emotion – it is the Problem is not the emotion – it is the attachment to the emotion.attachment to the emotion.

BiofeedbackBiofeedback Hippocampus and Amygdala send neurons that Hippocampus and Amygdala send neurons that

converge on Hypothalamusconverge on Hypothalamus In response to a blend of sensory information and In response to a blend of sensory information and

emotional assignment to that data, emotional assignment to that data, Hypothalamic Hypothalamic Releasing Hormones produce Releasing Hormones produce body changesbody changes

Neurons from Hypothalamus also project up to Neurons from Hypothalamus also project up to higher cortical brainhigher cortical brain This way, This way, individual can notice changes in arousalindividual can notice changes in arousal

• Respiratory rate, muscle tremor due to fight/flight hormones, Respiratory rate, muscle tremor due to fight/flight hormones, alertness, body temperature, sweating, cold hands, dry alertness, body temperature, sweating, cold hands, dry mouth, changes in appetite and thirst, bowel discomfortmouth, changes in appetite and thirst, bowel discomfort

Individual can Individual can CHOOSE to observe and actCHOOSE to observe and act to change to change the response – this isthe response – this is natural Biofeedback natural Biofeedback


Cerebral Cortex

Hypothalamus

Pituitary

Adrenal sits on Kidney


Corticotropin Releasing Hormone (CRH)Corticotropin Releasing Hormone (CRH) Pain, trauma, infection, low blood pressure, Pain, trauma, infection, low blood pressure,

exercise, low blood sugar, grief, loss, anger, exercise, low blood sugar, grief, loss, anger, fear causes fear causes hypothalamus to release CRHhypothalamus to release CRH

Anterior Anterior PituitaryPituitary responds by secreting responds by secreting Adrenocorticotropic Hormone (Adrenocorticotropic Hormone (ACTHACTH))

• Also called “Corticotropin”Also called “Corticotropin”

ACTH –ACTH – Adrenocorticotropic Hormone (aka Cortitropin)Adrenocorticotropic Hormone (aka Cortitropin)

Turns cholesterol into adrenal steroidsTurns cholesterol into adrenal steroids First into First into PregnenolonePregnenolone, then by adrenal , then by adrenal

zone…into…zone…into… Mineralo-corticosteroids (Mineralo-corticosteroids (aldosteronealdosterone))

• Electrolyte balance – salt reabsorption in kidneyElectrolyte balance – salt reabsorption in kidney Gluco-corticosteroids (Gluco-corticosteroids (cortisolcortisol))

• Glucose regulation, immune suppressionGlucose regulation, immune suppression Androgenic steroidsAndrogenic steroids

• AndrostenedioneAndrostenedione >Testosterone > Estrogens >Testosterone > Estrogens• DHEA-SulfateDHEA-Sulfate

CortisolCortisol

Stress increases metabolic demandStress increases metabolic demand Cortisol Cortisol ensures adequate glucose and Oensures adequate glucose and O22

to vital organs to vital organs Brain, heart, lung, muscleBrain, heart, lung, muscle

Cortisol helps aldosteroneCortisol helps aldosterone Increase renal sodium reabsorptionIncrease renal sodium reabsorption Allows Allows increased blood volumeincreased blood volume

CRH > ACTH > Cortisol releaseCRH > ACTH > Cortisol release Normal response to acute stressNormal response to acute stress

Cerebrum, hippocampus, amygdala > hypothalamic Cerebrum, hippocampus, amygdala > hypothalamic release of Corticotropin Releasing Hormonerelease of Corticotropin Releasing Hormone

Cortisol rises until concentration Cortisol rises until concentration high enough to high enough to produce negative feedbackproduce negative feedback to hippocampus and thus to hippocampus and thus to the hypothalamus to reduce CRH secretion - no to the hypothalamus to reduce CRH secretion - no prolonged cortisol excessprolonged cortisol excess

Abnormal condition – prolonged stressAbnormal condition – prolonged stress Damage and death to negative feedback neuronsDamage and death to negative feedback neurons in in

the hippocampus that help reduce CRH - the hippocampus that help reduce CRH - sustained sustained cortisol elevationcortisol elevation

Sapolsky RM et al. Endocr Sapolsky RM et al. Endocr Rev. 1986;7:284-301Rev. 1986;7:284-301

Stress > Adrenal Medulla produces Epinephrine & Stress > Adrenal Medulla produces Epinephrine & Norepinephrine > leads to ACTH release by PituitaryNorepinephrine > leads to ACTH release by Pituitary Additional release of cortisolAdditional release of cortisol

Prolonged Stress – Cortisol Prolonged Stress – Cortisol

Cortisol rises with acute stress, then dropsCortisol rises with acute stress, then drops Cortisol stays high with chronic stressCortisol stays high with chronic stress

““I feel stressed most days.”I feel stressed most days.” After variable period of time (years) After variable period of time (years)

cortisol then drops to low levelscortisol then drops to low levels ““I feel fatigued most days.”I feel fatigued most days.” Time to get to a low cortisol depends on Time to get to a low cortisol depends on

individual’s individual’s constitutionconstitution and and type of stressorstype of stressors and and frequency of exposurefrequency of exposure to stressors to stressors

Chronic StressChronic StressProlonged Elevated CortisolProlonged Elevated Cortisol

Increasing Increasing glucoseglucose levels levels Fat redistributesFat redistributes

From thigh/buttocks to From thigh/buttocks to abdomen & lower neckabdomen & lower neck

Insulin resistanceInsulin resistance, fluid retention, , fluid retention, high blood high blood pressurepressure

Decline in musculoskeletal quality and functionDecline in musculoskeletal quality and function Proteolysis of muscle, bone, connective tissueProteolysis of muscle, bone, connective tissue Inhibits protein formationInhibits protein formation

Orth DN, Kova WJ. The Adrenal Cortex. Williams Textbook of Orth DN, Kova WJ. The Adrenal Cortex. Williams Textbook of Endocrinology. 9Endocrinology. 9thth Ed. 1998:517-664. Ed. 1998:517-664.

Chronic Stress- Immune DysfunctionChronic Stress- Immune Dysfunction

Reduced number & function of…Reduced number & function of… Lymphocytes, eosinophils, basophils, Lymphocytes, eosinophils, basophils,

monophils, macrophages, neutrophilsmonophils, macrophages, neutrophils Reduced production of immune cell Reduced production of immune cell

signaling moleculessignaling molecules Reduced antibody productionReduced antibody production Increased frequency of infectious diseaseIncreased frequency of infectious disease

Munck A et al. Endocr Rev. 1984;5(1):25-44Munck A et al. Endocr Rev. 1984;5(1):25-44

CRH and AdrenalineCRH and Adrenaline Corticotropin Releasing Hormone Corticotropin Releasing Hormone increases increases

sympathetic (fight/flight)sympathetic (fight/flight) and and reduces reduces parasympathetic (calming) parasympathetic (calming) outflow from brain outflow from brain and spinal cordand spinal cord Increases epinephrine & norepinephrine (NE) Increases epinephrine & norepinephrine (NE)

from adrenal medulla from adrenal medulla • Which further increases ACTH secretion by pituitaryWhich further increases ACTH secretion by pituitary

Increases NE & neuropeptide Y in the….Increases NE & neuropeptide Y in the….• Heart, peripheral vessels, kidney, lung, pancreas, GI Heart, peripheral vessels, kidney, lung, pancreas, GI

tract, testicles, ovariestract, testicles, ovaries• Whole body effectsWhole body effects

CRH and AdrenalineCRH and Adrenaline

Result of increased CRH release by Result of increased CRH release by hypothalamushypothalamus Increased pulse, heart contraction strength, Increased pulse, heart contraction strength,

blood pressure, respiratory rate, liver release blood pressure, respiratory rate, liver release of glucose and fatty acids, kidney secretion of of glucose and fatty acids, kidney secretion of anti-diuretic hormone, and blood volumeanti-diuretic hormone, and blood volume

Other effects of chronic stress/cortisol/CRHOther effects of chronic stress/cortisol/CRH ThyroidThyroid function decreased function decreased Reproductive hormonesReproductive hormones disrupted disrupted

CRH, Adrenaline, and the GutCRH, Adrenaline, and the Gut Gastrointestinal effectsGastrointestinal effects

Stomach Stomach • Reduced gastric contractilityReduced gastric contractility• Reduced gastric emptyingReduced gastric emptying

ColonColon• Increased colon motilityIncreased colon motility• Rapid transit timesRapid transit times• Poor absorption of nutrients and waterPoor absorption of nutrients and water

Bloating, fullness, diarrhea, cramps, Bloating, fullness, diarrhea, cramps, exacerbation of IBS and Crohn’s Diseaseexacerbation of IBS and Crohn’s Disease

Tache Y et al. Am J Physiol Gastrointest Liver Physiol. 2001;280:G6173-77Tache Y et al. Am J Physiol Gastrointest Liver Physiol. 2001;280:G6173-77

Persistent stress reduces growth of probiotic Persistent stress reduces growth of probiotic bacteria bacteria (good bacteria)(good bacteria) LactobacillusLactobacillus BifidobacteriaBifidobacteria

And increases growth of potentially pathologic And increases growth of potentially pathologic bacteriabacteria E. ColiE. Coli ClostridiaClostridia EnterobacterEnterobacter

Lizko NN et al. Lizko NN et al. Nahrung. 1984;28:599-605Nahrung. 1984;28:599-605

CRH, Adrenaline, and the GutCRH, Adrenaline, and the Gut

Adrenal Fatigue ObservationsAdrenal Fatigue Observationson Physical Examon Physical Exam

Achilles' tendon reflex slow, low amplitudeAchilles' tendon reflex slow, low amplitude Slow pupillary reflexesSlow pupillary reflexes General quality of integument is poorGeneral quality of integument is poor

Ridged nailsRidged nails Hair thinningHair thinning Creased/lined fingerprintsCreased/lined fingerprints

Pale line above vermillion border Pale line above vermillion border

No citation – observation shared with other physicians following this topicNo citation – observation shared with other physicians following this topic

Prolonged CRH = DepressionProlonged CRH = Depression

CRH injected into animals’ brainsCRH injected into animals’ brains Increased locomotor activity (escape)Increased locomotor activity (escape) Startle response Startle response AnxietyAnxiety Stress-induced fighting (increases with dose)Stress-induced fighting (increases with dose) Reduced appetite, avoidance of unfamiliar or Reduced appetite, avoidance of unfamiliar or

threatening locationsthreatening locations Sutton RE et al. Nature. 1982;297:331-33Sutton RE et al. Nature. 1982;297:331-33

Lenz HG et al. Horm Metab Res. 1987;16(suppl):17-23Lenz HG et al. Horm Metab Res. 1987;16(suppl):17-23

These are the features of human depressionThese are the features of human depression

Depressed humans have Depressed humans have sustained 24hr sustained 24hr elevations of cortisolelevations of cortisol

Depression pattern is Depression pattern is blocked with CRH blocked with CRH receptor blockersreceptor blockers in experimental animals in experimental animals CRH receptor blocker drug named “CRH receptor blocker drug named “AntalarminAntalarmin””

Chrousos GP, Gold PW. JAMA. Chrousos GP, Gold PW. JAMA. 1992;267(9):1244-521992;267(9):1244-52

Habib K et al. PNAS. Habib K et al. PNAS. 2000;2000;97(11):97(11):6079–60846079–6084

Prolonged CRH = DepressionProlonged CRH = Depression

High HPA Axis Activity Low HPA Axis ActivityHigh HPA Axis Activity Low HPA Axis Activity (Elevated Cortisol)(Elevated Cortisol) (Low Cortisol)(Low Cortisol)

Chronic StressChronic Stress Melancholic DepressionMelancholic Depression AnorexiaAnorexia Type 2 DiabetesType 2 Diabetes Syndrome XSyndrome X Premenstrual SyndromePremenstrual Syndrome

Adrenal InsufficiencyAdrenal Insufficiency Chronic Fatigue SyndChronic Fatigue Synd FibromyalgiaFibromyalgia Postpartum DepressionPostpartum Depression PTSDPTSD Rheumatoid Arthritis Rheumatoid Arthritis

exacerbationexacerbation

Chrousos GP, Gold PW. JAMA. 1992;267(9):1244-52Chrousos GP, Gold PW. JAMA. 1992;267(9):1244-52

Depression/Anxiety & Heart HealthDepression/Anxiety & Heart Health Depression and anxiety Depression and anxiety increase the risk of death increase the risk of death

after heart attackafter heart attack and can lead to diabetes and can lead to diabetes

Exercise works as well as pharmaceutical drugsExercise works as well as pharmaceutical drugs for depression at 4 months for depression at 4 months

Drugs worked more quickly but effects equal at 4 monthsDrugs worked more quickly but effects equal at 4 months

• Blumenthal JA et al. Effects of Exercise Training on Older Patients with Blumenthal JA et al. Effects of Exercise Training on Older Patients with Major Depression. Arch Intern Med. 1999;159:2349-2356. Major Depression. Arch Intern Med. 1999;159:2349-2356.

• Frasure-Smith N, Lesperance F. Depression and Anxiety as Predictors of 2-Frasure-Smith N, Lesperance F. Depression and Anxiety as Predictors of 2-Year Cardiac Events in Patients With Stable Coronary Artery Disease. Arch Year Cardiac Events in Patients With Stable Coronary Artery Disease. Arch Gen Psychiatry. 2008;65(1):62-71Gen Psychiatry. 2008;65(1):62-71

• Carney RM, et al. Depression and five-year survival following acute Carney RM, et al. Depression and five-year survival following acute myocardial infarction: a prospective study. Journal of Affective Disorders, myocardial infarction: a prospective study. Journal of Affective Disorders, 2008. doi:10.1016/j.jad.2007.12.0052008. doi:10.1016/j.jad.2007.12.005

Emotion and Heart HealthEmotion and Heart Health

High levels of High levels of anger anger 3.15-fold increase in future heart disease3.15-fold increase in future heart disease Dose-dependant (more anger = more risk)Dose-dependant (more anger = more risk)

Kawachi I et al. Circulation. Kawachi I et al. Circulation. 1996;94:2090-951996;94:2090-95

Strong experience of Strong experience of anxietyanxiety 3.2-fold increase in heart attack risk3.2-fold increase in heart attack risk

Kawachi I et al. Circulation. Kawachi I et al. Circulation. 1994;90:2225-22291994;90:2225-2229

Excessive Excessive worry worry 2.4-fold increase in heart attack risk2.4-fold increase in heart attack risk Kubzansky LD et al. Circulation. Kubzansky LD et al. Circulation.

1997;95:818-8241997;95:818-824

Emotion and Heart HealthEmotion and Heart Health Positive AffectPositive Affect

““Feelings that reflect a level of pleasurable Feelings that reflect a level of pleasurable engagementengagement with the environment” (environment = with the environment” (environment = everything outside the self)everything outside the self)

Happiness, joy, excitement, enthusiasm, and Happiness, joy, excitement, enthusiasm, and contentmentcontentment

65-99yo with65-99yo with higher positive affect 53% (half) as higher positive affect 53% (half) as likely to dielikely to die in 2 yr study in 2 yr study

Ostir, GV. J Am Geriatric Soc Ostir, GV. J Am Geriatric Soc 2000;48:473–4782000;48:473–478

660 adults median age 63. Above-average 660 adults median age 63. Above-average positive affect group positive affect group lived 7.5 years longerlived 7.5 years longer than than unhappier half.unhappier half.

Levy BR. J Personality and Social Psychology Levy BR. J Personality and Social Psychology 2002;83:261–2702002;83:261–270

Happiness produces…Happiness produces… Lower cortisolLower cortisol on working and nonworking on working and nonworking

days, reduced fibrinogen stress responses, days, reduced fibrinogen stress responses, and and lower ambulatory heart ratelower ambulatory heart rate in men. in men. • Independent of age, socioeconomic status, Independent of age, socioeconomic status,

smoking, body mass and psychological distress. smoking, body mass and psychological distress. Steptoe A.Neurobiology of Aging 26S (2005) Steptoe A.Neurobiology of Aging 26S (2005)

S108–S112S108–S112

Emotion and Heart HealthEmotion and Heart Health

Theory of Progesterone StealTheory of Progesterone Steal(aka: Pregnenolone Steal - or - Estrogen Dominance)(aka: Pregnenolone Steal - or - Estrogen Dominance)

Adrenal Fatigue assumes an Adrenal Fatigue assumes an inability to keep up inability to keep up with cortisol productionwith cortisol production demanded by continued demanded by continued hypothalamic CRH elevationhypothalamic CRH elevation

Progesterone (+/-pregnenolone) is “stolen” Progesterone (+/-pregnenolone) is “stolen” to to make more cortisolmake more cortisol

Low levels of progesterone out of proportion to Low levels of progesterone out of proportion to estrogen levels = Estrogen Dominanceestrogen levels = Estrogen Dominance Reinforced by chronic stress causing increased Reinforced by chronic stress causing increased

central abdominal fatcentral abdominal fat This fat increases total body estrogenThis fat increases total body estrogen

Complicated perimenopausal anovulationComplicated perimenopausal anovulation Ovulation Ovulation leaves behind the corpeus luteum which leaves behind the corpeus luteum which

secretes progesteronesecretes progesterone for the premenstrual week, for the premenstrual week, “runs out” of progesterone, and triggers menstrual “runs out” of progesterone, and triggers menstrual periodperiod

This theory presumes that This theory presumes that fixing adrenal function fixing adrenal function and estrogen dominanceand estrogen dominance go hand-in-hand go hand-in-hand

I can find no studiesI can find no studies (See Case 4) (See Case 4) My Clinical experience – My Clinical experience – progesterone is calmingprogesterone is calming

• Less insomnia & anxiety, reduction in hot flashesLess insomnia & anxiety, reduction in hot flashes


Progesterone is metabolized in the liver to Progesterone is metabolized in the liver to allopregnanoloneallopregnanolone which is a GABA receptor which is a GABA receptor agonist agonist CalmingCalming Helpful for Helpful for anxiety, insomnia, hot flashesanxiety, insomnia, hot flashes Topical progesterone bypasses the liverTopical progesterone bypasses the liver

• No studies on its effect on GABA receptorNo studies on its effect on GABA receptor• My clinical experience – topical progesterone easily adjusted My clinical experience – topical progesterone easily adjusted

to produce same effects aboveto produce same effects above

Is supplemental progesterone effective because Is supplemental progesterone effective because of its of its primary action as a GABA receptor agonistprimary action as a GABA receptor agonist or because it is or because it is replacing a deficiencyreplacing a deficiency created by created by chronic stress response by adrenals?chronic stress response by adrenals?


Chronic Stress and ThyroidChronic Stress and Thyroid Hypothalamic CRH neurons project onto Hypothalamic CRH neurons project onto

hypothalamic Thyrotropin Releasing Hormone hypothalamic Thyrotropin Releasing Hormone (TRH) neurons that govern pituitary’s release of (TRH) neurons that govern pituitary’s release of Thyroid Stimulating Hormone (TSH)Thyroid Stimulating Hormone (TSH)

Chronic stress reduces TRHChronic stress reduces TRH …lower thyroid fxn …lower thyroid fxn Low TSH, normal T4/T3 levelsLow TSH, normal T4/T3 levels associated with associated with

increased mortality in >60yo humansincreased mortality in >60yo humans• Indicator of chronic stressIndicator of chronic stress

Adding thyroxine (T4) in borderline hypothyroidism is Adding thyroxine (T4) in borderline hypothyroidism is no better than placebo for cognitive function, mood, or no better than placebo for cognitive function, mood, or wellbeingwellbeing

Pollock MA et Pollock MA et al. BMJ. 2001;323:891-95al. BMJ. 2001;323:891-95

Upstream AntecedentsUpstream AntecedentsDownstream DiagnosisDownstream Diagnosis

Chronic StressChronic Stress

CRH elevationCRH elevation

Cortisol elevationCortisol elevation

Depression, anxiety, Depression, anxiety, fatigue, IBS, hypothyroidfatigue, IBS, hypothyroidInsomnia, central weight,Insomnia, central weight,diabetes, PMS, high BPdiabetes, PMS, high BPpolycystic ovaries, polycystic ovaries, heart diseaseheart disease

Chinese Medicine and AdrenalsChinese Medicine and Adrenals


Debate: The Debate: The Root of All DiseaseRoot of All Disease boils down to boils down to one of two schools of thoughtone of two schools of thought

Kidney JingKidney Jing (dependent on KI Yin) (dependent on KI Yin) Ancestral/genetic inheritanceAncestral/genetic inheritance Lifestyle stress, Adrenal FatigueLifestyle stress, Adrenal Fatigue Enters body at conceptionEnters body at conception Leaves body with last breathLeaves body with last breath

Spleen QiSpleen Qi Dependent upon and responsible for proper nutrition, Dependent upon and responsible for proper nutrition,

gastrointestinal function, and immune function gastrointestinal function, and immune function

Three Treasures

Jing

Qi

Shen


Adrenals are part of the KidneyAdrenals are part of the Kidney Kidney is the solid organ manifesting the Kidney is the solid organ manifesting the

Water ElementWater Element Adrenal Deficiency ~ Adrenal Deficiency ~ Water DeficiencyWater Deficiency

• Kidney Yin DeficiencyKidney Yin Deficiency• Kidney Yang DeficiencyKidney Yang Deficiency

Underlying any Yang Deficiency is Kidney Yin DeficiencyUnderlying any Yang Deficiency is Kidney Yin Deficiency

Five ElementsSystem of

Correspondences

Fire

Wood

Water Metal

Earth

HomeostasisHomeostasisSheng – Ke CycleSheng – Ke Cycle

Controlling or Dampening Influence

Supporting or Augmenting Influence

System Self-Correction (in the short term)

Five Element CorrespondencesFive Element Correspondences Water (Kidney, Bladder)Water (Kidney, Bladder)

Philosopher, contemplative, remarkably strong Philosopher, contemplative, remarkably strong or weak or weak motivation/willpowermotivation/willpower, sensitive to , sensitive to guilt guilt and fearand fear, hurt deeply by abuse, bladder , hurt deeply by abuse, bladder infections, kidney stones, incontinence, joint infections, kidney stones, incontinence, joint pain, low back pain, pain, low back pain, inner chillinner chill, music, hearing , music, hearing problems, throat, winter, black, north, salty, problems, throat, winter, black, north, salty, cold or heat intolerancecold or heat intolerance

Adrenal Gland governed by Water ElementAdrenal Gland governed by Water Element• Symptoms produced by imbalances in Symptoms produced by imbalances in WoodWood and and

FireFire Elements Elements triggered by Water deficiencytriggered by Water deficiency

Wood (Liver, Gallbladder) Wood (Liver, Gallbladder) DrivenDriven, multiple projects, , multiple projects, movementmovement, CEO, , CEO,

anger/anxietyanger/anxiety, tight traps/lateral neck/IT band, , tight traps/lateral neck/IT band, TMJ, migraine, TMJ, migraine, headachesheadaches, caffeine , caffeine sensitivity, fibromyalgia, blue/green, sensitivity, fibromyalgia, blue/green, sour/citrus, Spring, expansion, insomnia (esp. sour/citrus, Spring, expansion, insomnia (esp. sleep maintenance sleep maintenance 11pm-3am11pm-3am), east), east

Five Element CorrespondencesFive Element Correspondences

Fire (Heart, Small Intestine, Pericardium, Fire (Heart, Small Intestine, Pericardium, Triple Energizer)Triple Energizer) CreativeCreative, CEO, joy, , CEO, joy, awarenessawareness, ,

love/attachment, mania, love/attachment, mania, palpitationspalpitations, , insomnia (esp. insomnia (esp. sleep initiationsleep initiation), ), hot flasheshot flashes, , night sweats, cardiac disease, dysrhythmias, night sweats, cardiac disease, dysrhythmias, red/orange, bitter/roasted, summer, southred/orange, bitter/roasted, summer, south


Earth (Spleen, Stomach)Earth (Spleen, Stomach) NurturingNurturing, worry/obsession, , worry/obsession, GI issuesGI issues

(loose stools, gastritis, bloating, abd pain), (loose stools, gastritis, bloating, abd pain), sinusitissinusitis, cysts, tumors, lumps, dampness, , cysts, tumors, lumps, dampness, obesity, obesity, chronic fatigue (multifactorial)chronic fatigue (multifactorial), , sweet, sweet, dampnessdampness (cysts, edema), (cysts, edema), yellow/brown, transitions of seasons, yellow/brown, transitions of seasons, center of compass positionscenter of compass positions


Metal (Lung, Large Intestine)Metal (Lung, Large Intestine) RespiratoryRespiratory,, skin skin disorders (“3rd lung”), disorders (“3rd lung”),

constipation, dryness, constipation, dryness, sense of dutysense of duty,, grief, grief, lossloss, depression (multifactorial), , depression (multifactorial), flavorful/spicy, white/grey/colorless, autumn, flavorful/spicy, white/grey/colorless, autumn, westwest


Yin & Yang Deficiency & ExcessYin & Yang Deficiency & Excess

Yin DeficiencyYin Deficiency

Yang will appear in Yang will appear in excess with heat, excess with heat,

dryness, thirst, dryness, thirst, back pain, stiffness back pain, stiffness insomnia, loss of insomnia, loss of

willpower to follow willpower to follow through with through with

action. This is action. This is Empty Heat Empty Heat

compared to Full compared to Full Heat (tonify rather Heat (tonify rather

than disperse).than disperse).

Yang DeficiencyYang Deficiency

Yin will appear in Yin will appear in excess with cold, excess with cold,

fluid retention, fluid retention, chills, back pain, chills, back pain, daytime fatigue, daytime fatigue, low libido, loss of low libido, loss of

willpower to willpower to initiate action. initiate action. This is Empty This is Empty Cold (tonify Cold (tonify rather than rather than disperse).disperse).

Yang ExcessYang Excess

Yang appears Yang appears in excess with in excess with

Full Heat – Full Heat – migraines, migraines, pressure, pressure,

bloating, mania, bloating, mania, hypertension, hypertension,

anger, anger, insomnia, fever. insomnia, fever.

Full Heat Full Heat (disperse rather (disperse rather

than tonify).than tonify).

Yin ExcessYin Excess

Yin appears in Yin appears in excess with Full excess with Full

Cold – usually due Cold – usually due to Wind Cold to Wind Cold

invasion. Stiffness, invasion. Stiffness, contraction of contraction of

tendons, chilliness, tendons, chilliness, severe menstrual or severe menstrual or

abdominal pain, abdominal pain, fluid retention and fluid retention and

watery-loose watery-loose discharges discharges

including stools.including stools.

The Yo-Yo Rest-Stress CycleThe Yo-Yo Rest-Stress Cycle

What to Do?What to Do? Whip the adrenalsWhip the adrenals to give you more energy to give you more energy

Sustained use of hormones (cortisol, pregnenolone, Sustained use of hormones (cortisol, pregnenolone, DHEA, thyroid) and other supplementsDHEA, thyroid) and other supplements

Some brief gain before reaching the cliff’s edgeSome brief gain before reaching the cliff’s edge (Bad Idea)(Bad Idea)

Alter your LifestyleAlter your Lifestyle Acknowledge stressorsAcknowledge stressors Adequate sleepAdequate sleep Appropriate exerciseAppropriate exercise Nutritious dietNutritious diet Moving meditationMoving meditation PsychotherapyPsychotherapy Short term supplementsShort term supplements

Relaxation TechniquesRelaxation Techniques

The Five AgreementsThe Five Agreementsby Don Miguel Ruizby Don Miguel Ruiz

1. Be Impeccable With Your Word. 1. Be Impeccable With Your Word. 2. Don't Take Anything Personally. 2. Don't Take Anything Personally.

3. Don't Make Assumptions. 3. Don't Make Assumptions. 4. Always Do Your Best.4. Always Do Your Best.

5. Be Skeptical, But Learn to Listen.5. Be Skeptical, But Learn to Listen.

Relaxation TechniquesRelaxation Techniques

Cognitive Behavioral Therapy or other Cognitive Behavioral Therapy or other PsychotherapyPsychotherapy

Moderate Graded ExerciseModerate Graded Exercise Tai ChiTai Chi YogaYoga MeditationMeditation Guided ImageryGuided Imagery

Cognitive Behavioral TherapyCognitive Behavioral Therapy Form of psychotherapy – goal is to identify, modify and Form of psychotherapy – goal is to identify, modify and

change factors that may be maintaining symptoms change factors that may be maintaining symptoms Individualized therapy to improve patternsIndividualized therapy to improve patterns

Rest, activity, sleep patterns, exercise capacity, cognition, Rest, activity, sleep patterns, exercise capacity, cognition, coping strategies, problem solving, reducing stress, anxiety and coping strategies, problem solving, reducing stress, anxiety and depressiondepression

Well studied and effective in Chronic Fatigue SyndromeWell studied and effective in Chronic Fatigue Syndrome Meta analysis reviewed Meta analysis reviewed 10,768 publications published on 10,768 publications published on

interventions for chronic fatigue syndromeinterventions for chronic fatigue syndrome and selected 70 that and selected 70 that met the selection criteriamet the selection criteria

• Cognitive Behavioral Therapy hadCognitive Behavioral Therapy had best evidence of best outcomes best evidence of best outcomes • Moderate Graded Exercise was 2Moderate Graded Exercise was 2ndnd best evidence/outcomes best evidence/outcomes Chambers D et al. Chambers D et al. J R Soc MedJ R Soc Med. 2006;99:506-520. 2006;99:506-520

Improving fatigue symptoms and cortisol levelsImproving fatigue symptoms and cortisol levels Possible exception – Possible exception – very low morning cortisol may predict less very low morning cortisol may predict less

response to CBTresponse to CBT

Professional burnoutProfessional burnout (exhaustion, fatigue, (exhaustion, fatigue, feelings of reduced competence)feelings of reduced competence) 14 sessions of psychotherapy14 sessions of psychotherapy Low morning cortisol prior to series of Low morning cortisol prior to series of

treatments - increased after 14 sessionstreatments - increased after 14 sessions Mommersteeg PM. Health Psychology. 2006;25(2): 243-248Mommersteeg PM. Health Psychology. 2006;25(2): 243-248

PsychotherapyPsychotherapy

ExerciseExercise

Moderate Graded ExerciseModerate Graded Exercise Exercise with moderate exertion that gradually increases in Exercise with moderate exertion that gradually increases in

intensity over 6-8 weeksintensity over 6-8 weeks• Avoids over-exertion which causes post-exercise worsening of Avoids over-exertion which causes post-exercise worsening of

fatigue conditionfatigue condition 148 patients with Chronic Fatigue Syndrome randomized to 148 patients with Chronic Fatigue Syndrome randomized to

moderate graded exercise versus standard medical caremoderate graded exercise versus standard medical care• Highly significant improvements in Highly significant improvements in physical functioning, sleep, physical functioning, sleep,

fatigue, mood, and disabilityfatigue, mood, and disability Powell P et al. BMJ 2001; 322 : 387Powell P et al. BMJ 2001; 322 : 387

Cochrane review of 9 randomized trialsCochrane review of 9 randomized trials Moderate graded exercise Moderate graded exercise effective for fatigueeffective for fatigue Better than prozac, though Better than prozac, though prozac plus exercise superiorprozac plus exercise superior

Edmonds M et al. CoEdmonds M et al. Cochrane Database of Systematic Reviewschrane Database of Systematic Reviews 2004, Issue 3 2004, Issue 3

Tai ChiTai Chi

Moving MeditationMoving Meditation Equivalent to moderate physical exerciseEquivalent to moderate physical exercise

((walking 6mphwalking 6mph) and ) and superior to sitting meditationsuperior to sitting meditation and neutral reading in 96 men and womenand neutral reading in 96 men and women Reducing stress-induced elevations of urine Reducing stress-induced elevations of urine

catecholamines (stress hormones), salivary cortisol, catecholamines (stress hormones), salivary cortisol, pulse, and blood pressurepulse, and blood pressure

Jin P. J Psychosom Res. Jin P. J Psychosom Res. 1992;36(4);36-701992;36(4);36-70

Tai ChiTai Chi

After heart attack, Tai Chi more effective than moderate After heart attack, Tai Chi more effective than moderate exercise or support group in exercise or support group in lowering diastolic BPlowering diastolic BP

Channer KS et al. Postgrad Med J 1996; 72: 349-351Channer KS et al. Postgrad Med J 1996; 72: 349-351 66 Tai Chi practitioners controlled for experience and 66 Tai Chi practitioners controlled for experience and

time of day. time of day. Pre and post…Pre and post… Serum cortisol, norepinephrine, heart rate, Profile of Mood States, Trait Serum cortisol, norepinephrine, heart rate, Profile of Mood States, Trait

Anxiety InventoryAnxiety Inventory More experienced practitioners had higher pulse ratesMore experienced practitioners had higher pulse rates

Slowly learned skill which Slowly learned skill which will result in more benefits with experiencewill result in more benefits with experience Mood improvedMood improved and remained elevated and remained elevated >> 1 hour 1 hour Reduced tension, anger, fatigue, depression, confusion, Reduced tension, anger, fatigue, depression, confusion,

anxiety, cortisol, and norepinephrineanxiety, cortisol, and norepinephrine Tai Chi has low physical workload - 50% of VO2 maxTai Chi has low physical workload - 50% of VO2 max

Jin P. J Psychosom Res. 1989;33;197-206Jin P. J Psychosom Res. 1989;33;197-206

MeditationMeditation Sitting Meditation Sitting Meditation effective for relieving stresseffective for relieving stress

Improves cortisol, pulse, blood pressure, total protein, Improves cortisol, pulse, blood pressure, total protein, reaction timereaction time

Sudsuang R et al. Physiol Behav. 1991 Sudsuang R et al. Physiol Behav. 1991 Sep;50(3):543-8Sep;50(3):543-8

Compassion meditation vs discussion groupCompassion meditation vs discussion group Cortisol, IL-6, Profile of Mood States, Trier Social Cortisol, IL-6, Profile of Mood States, Trier Social

Stress Test measured before and afterStress Test measured before and after No group differenceNo group difference Subset who Subset who meditated longer than the medianmeditated longer than the median had had

significant improvements in IL-6, POMS, TSST but significant improvements in IL-6, POMS, TSST but not cortisolnot cortisol

Pace TWW et al. Psychoneuroendocrin Pace TWW et al. Psychoneuroendocrin 2009;24(1):87-882009;24(1):87-88

Sitting Meditation Sitting Meditation not as effective as Tai Chinot as effective as Tai Chi Jin P. J Psychosom Res. 1992;36(4);36-70Jin P. J Psychosom Res. 1992;36(4);36-70

YogaYoga

Women in 3-month yoga training versus Women in 3-month yoga training versus wait list controlswait list controls ImprovedImproved perceived stress, State and Trait perceived stress, State and Trait

Anxiety, well-being, vigor, fatigue, depression, Anxiety, well-being, vigor, fatigue, depression, pain relief, salivary cortisol levelspain relief, salivary cortisol levels

Michalsen A et al. Med Sci Monit, 2005; 11(12): CR555-561Michalsen A et al. Med Sci Monit, 2005; 11(12): CR555-561

EffectiveEffective in women with breast cancer in women with breast cancer Fatigue, well-being, sleep, cortisol levelsFatigue, well-being, sleep, cortisol levels

Raghavendra RM J Clin Oncol 28:15s, 2010 Raghavendra RM J Clin Oncol 28:15s, 2010 (suppl; abstr 9099 (suppl; abstr 9099

Guided ImageryGuided Imagery

13 week program of Bonny Guided 13 week program of Bonny Guided Imagery and Music Imagery and Music Profile of Mood States testProfile of Mood States test Morning cortisolMorning cortisol Tests baseline, after 13 wks, & 6 months laterTests baseline, after 13 wks, & 6 months later

Improved mood, depression states, and Improved mood, depression states, and morning cortisolmorning cortisol

McKinney CH. Health Psychology. McKinney CH. Health Psychology. 1997:16(4):390-401997:16(4):390-40

PerspectivePerspective Moving MeditationMoving Meditation

Tai Chi superior to Sitting Meditation for improving Tai Chi superior to Sitting Meditation for improving stress response stress response Jin P. J Psychosom Res. 1992;36(4);36-70Jin P. J Psychosom Res. 1992;36(4);36-70

• I assume a likely similar finding for yoga, but have not seen I assume a likely similar finding for yoga, but have not seen comparison study.comparison study.

• I assume that I assume that very active and rhythmic engagement of spine very active and rhythmic engagement of spine and pelvisand pelvis is the mechanism for this difference is the mechanism for this difference

Experience GrowsExperience Grows Tai Chi studyTai Chi study

• More experienced practitioners had higher pulse More experienced practitioners had higher pulse ratesrates

Slowly learned skill which Slowly learned skill which will result in more benefits with will result in more benefits with experience experience Jin P. J Psychosom Res. 1989;33;197-206Jin P. J Psychosom Res. 1989;33;197-206

Meditation studyMeditation study• Subset who Subset who meditated longer than the medianmeditated longer than the median had had

significant improvements in stress responsesignificant improvements in stress responsePace TWW et al. Pace TWW et al.

Psychoneuroendocrin 2009;24(1):87-88Psychoneuroendocrin 2009;24(1):87-88

A Few CasesA Few Cases

62yo F with fatigue for 5 months and feels cold, 62yo F with fatigue for 5 months and feels cold, sweaty all day. Chronic insomnia. sweaty all day. Chronic insomnia.

Major stressor:Major stressor: frequent interstate travel to care frequent interstate travel to care for father with dementia in setting of lack of for father with dementia in setting of lack of support by local sibling and intermittent sibling support by local sibling and intermittent sibling conflictconflict

Low basal body temp 97.3-97.7. Long flu-like Low basal body temp 97.3-97.7. Long flu-like illness 1 month earlier complicated her fatigueillness 1 month earlier complicated her fatigue

AcupunctureAcupuncture and (Chinese Herbal) and (Chinese Herbal) Minor Minor BupleurumBupleurum started for 4-6 weeks, labs drawn. started for 4-6 weeks, labs drawn.

TSH 1.56, Free T3 2.9, Free T4 1.37, RT3 30, TSH 1.56, Free T3 2.9, Free T4 1.37, RT3 30, normal CBC and Chem 7normal CBC and Chem 7

Case 1: Cortisol High, DHEA lowCase 1: Cortisol High, DHEA low

Case 1: Cortisol High, DHEA lowCase 1: Cortisol High, DHEA low

Adrenocortex Stress ProfileAdrenocortex Stress Profile(saliva sampling x 4 in one day)(saliva sampling x 4 in one day)

Case 1: Treatment PlanCase 1: Treatment Plan Encourage adequate rest and sleepEncourage adequate rest and sleep MeditationMeditation training referral training referral AcupunctureAcupuncture

Tonify Kidney Yin and settle Heart ShenTonify Kidney Yin and settle Heart Shen CorticoB5B6 CorticoB5B6 (Vit C 250mg, B6 100mg, (Vit C 250mg, B6 100mg,

pantothenic acid 500mg, magnesium 75mg, pantothenic acid 500mg, magnesium 75mg, citrus bioflavanoid complex 100mg) 1 tablet citrus bioflavanoid complex 100mg) 1 tablet three times per daythree times per day

L-TheanineL-Theanine 200mg twice per day 200mg twice per day GABA GABA 700mg daily in morning700mg daily in morning DHEADHEA 25mg daily in morning 25mg daily in morning Rescue FormulaRescue Formula 3 twice per day (TCM: Heart 3 twice per day (TCM: Heart

Shen disturbance)Shen disturbance)

Case 1: Follow-Up Case 1: Follow-Up

Over the next 3 weeks, GABA increased Over the next 3 weeks, GABA increased gradually to 1400mg twice per day and gradually to 1400mg twice per day and

L-theanine increased to 400mg in AM, 200mg in L-theanine increased to 400mg in AM, 200mg in PMPM

Ambien stopped.Ambien stopped. By week 5-6, By week 5-6, Fatigue 75% betterFatigue 75% better, insomnia , insomnia

improving intermittently with no ambienimproving intermittently with no ambien Eventually had to use intermittent lower dose Eventually had to use intermittent lower dose

Ambien but able to remain of nightly higher doseAmbien but able to remain of nightly higher dose

Case 2: Cortisol LowCase 2: Cortisol Low 71yo male with 1 year of 71yo male with 1 year of worsening profound worsening profound

fatiguefatigue. Previously athletic. Now so tired that . Previously athletic. Now so tired that “the other day I didn’t have the energy to read “the other day I didn’t have the energy to read the newspaper.”the newspaper.”

Stressors:Stressors: stressful years in business, divorce, stressful years in business, divorce, two decades of simple carb diet, prostate cancer two decades of simple carb diet, prostate cancer 5 years ago, major stress including extensive 5 years ago, major stress including extensive and prolonged anger 4-5 years ago, low and prolonged anger 4-5 years ago, low testosteronetestosterone

Other: low back pain, dry mouth, tendency to Other: low back pain, dry mouth, tendency to anger when stressedanger when stressed

Exam: horizontal creases in fingerprints, thinning Exam: horizontal creases in fingerprints, thinning hair and eyebrows, pitted nails, normal hair and eyebrows, pitted nails, normal heart/lung/abdomen exam. heart/lung/abdomen exam.

Case 2: Cortisol Low, DHEA normCase 2: Cortisol Low, DHEA norm

Adrenal Fatigue – InducedAdrenal Fatigue – InducedConnective Tissue Dysfunction?Connective Tissue Dysfunction?

Ridged Fingernails

Case 2 - Considerably worse than this until 2 months into treatment

Creased Fingerprints

Suggests deficiency Connective Tissue integrity – often improves

with resolution of fatigue

Adrenocortex Stress ProfileAdrenocortex Stress Profile(saliva sampling x 4 in one day)(saliva sampling x 4 in one day)

Case 2: Treatment PlanCase 2: Treatment Plan AcupunctureAcupuncture weekly weekly

Kidney Yin, Ming Men tonified (10 treatments over 3 months)Kidney Yin, Ming Men tonified (10 treatments over 3 months) Meditation – “too time consuming”Meditation – “too time consuming” Encourage rest when needed and Encourage rest when needed and adequate sleepadequate sleep

Chinese Medicine (Kidney Yin Deficiency)Chinese Medicine (Kidney Yin Deficiency) Nourish the RootNourish the Root 4 tablets at bedtime 4 tablets at bedtime

Gut mucosal and digestive/absorption support:Gut mucosal and digestive/absorption support: Glutagenics Glutagenics ( L-glutamine 3 grams, DGL 200mg, Aloe ( L-glutamine 3 grams, DGL 200mg, Aloe

50mg per tsp) 1 teaspoon twice per day50mg per tsp) 1 teaspoon twice per day Bio-Gest Bio-Gest (Betaine HCl, Ox Bile concentrate, pancreatic (Betaine HCl, Ox Bile concentrate, pancreatic

enzymes) 2-4 capsules with each meal. enzymes) 2-4 capsules with each meal. Ultra Flora Plus DFUltra Flora Plus DF Capsules (Lactobacillus species and Capsules (Lactobacillus species and

Bifidobacteria 15 billion colonies per capsule) 2/dayBifidobacteria 15 billion colonies per capsule) 2/day

Case 2: Treatment PlanCase 2: Treatment Plan Adrenal Support:Adrenal Support: AdresetAdreset (1 tablet: cordyceps 400mg, panax ginseng 200mg, (1 tablet: cordyceps 400mg, panax ginseng 200mg,

rhodiola 50mg) 1 tablet three times per dayrhodiola 50mg) 1 tablet three times per day CorticoB5B6 CorticoB5B6 (1 tablet: Vit C 250mg, B6 100mg, pantothenic acid (1 tablet: Vit C 250mg, B6 100mg, pantothenic acid

500mg, magnesium 75mg, citrus bioflavanoid complex 100mg) 500mg, magnesium 75mg, citrus bioflavanoid complex 100mg) 1 tablet three times per day1 tablet three times per day PregnenolonePregnenolone (1 capsule: 30mg) 1 capsule in morning and (1 capsule: 30mg) 1 capsule in morning and

afternoon no later than 2pmafternoon no later than 2pm EPA-DHA 720EPA-DHA 720 (Fish Oil with EPA 430mg, DHA 290mg per gelcap) (Fish Oil with EPA 430mg, DHA 290mg per gelcap)

2 twice per day2 twice per day Collagen Collagen JS (Pure Encapsulations- Hydrolyzed type II collagen JS (Pure Encapsulations- Hydrolyzed type II collagen

complex from chicken sternal cartilege 500mg/capsule) 4 capsules complex from chicken sternal cartilege 500mg/capsule) 4 capsules per day with meals and 8oz waterper day with meals and 8oz water

Adrenal RebuilderAdrenal Rebuilder (porcine adrenal, gonad, hypothalamus and (porcine adrenal, gonad, hypothalamus and pituitary concentrates processed to remove hormones) 1 pill three pituitary concentrates processed to remove hormones) 1 pill three times per day for one week and then increase to 2 three times per times per day for one week and then increase to 2 three times per day on week 2day on week 2

Case 2: Follow-UpCase 2: Follow-Up 4 weeks4 weeks: 85-90% improved compared to 2 years prior. : 85-90% improved compared to 2 years prior.

Beginning to exerciseBeginning to exercise 6 weeks6 weeks: 95% improved. Leg pressed 400lbs 12 : 95% improved. Leg pressed 400lbs 12

repetitions/set for 6 sets at age 72.repetitions/set for 6 sets at age 72. 3 months:3 months: 100% resolved to normal energy. 100% resolved to normal energy. Blood Blood

pressure high in 150s for 1st timepressure high in 150s for 1st time. Stopped Adreset, . Stopped Adreset, Collagen, Pregenonlone, and BiogestCollagen, Pregenonlone, and Biogest

5 months5 months: Blood pressure normal, Fatigue still resolved. : Blood pressure normal, Fatigue still resolved. Hair and eyebrows thick and bushy after prior thinning. Hair and eyebrows thick and bushy after prior thinning. Pitted/ridged fingernails normalized. All supplements Pitted/ridged fingernails normalized. All supplements stopped.stopped.

7 months to 1 year later:7 months to 1 year later: Added testosterone in face of Added testosterone in face of history of prostate cancer with close PSA monitoring. history of prostate cancer with close PSA monitoring. Athletic. No fatigue. VibrantAthletic. No fatigue. Vibrant

Risks of Treatment of Risks of Treatment of “Adrenal Fatigue”“Adrenal Fatigue”

Expense (short term but significant)Expense (short term but significant) High Blood Pressure High Blood Pressure

Resolved by lowering DHEA, pregnenolone, glandularResolved by lowering DHEA, pregnenolone, glandular

InsomniaInsomnia Resolved by lowering DHEA, pregnenolone, glandularResolved by lowering DHEA, pregnenolone, glandular

DHEA impairs function of TamoxifenDHEA impairs function of Tamoxifen (used in ER (used in ER positive breast cancer) positive breast cancer) when level of when level of DHEA-Sulfate DHEA-Sulfate >> 90 90

Failure to recognize other causes of fatigueFailure to recognize other causes of fatigue

Case 3: Case 3: Cortisol & DHEA Normal, Glucose HighCortisol & DHEA Normal, Glucose High

38 yo M - 38 yo M - fasting glucose 106fasting glucose 106 with no diabetes with no diabetes risk factors, excellent nutrition, strong family risk factors, excellent nutrition, strong family history of early heart disease. history of early heart disease.

Normal blood pressure, BMI 21.5. Tendency to Normal blood pressure, BMI 21.5. Tendency to irritabilityirritability, some fatigue if not rested, back ache, , some fatigue if not rested, back ache, easily chilled, frequent viral infectionseasily chilled, frequent viral infections

Stressors:Stressors: demanding career, demanding career, family commitments, family commitments, inadequate sleepinadequate sleep due to work due to work and variety of outside interestsand variety of outside interests

Case 3: Case 3: Cortisol Normal, Glucose HighCortisol Normal, Glucose High

Adrenocortex Stress ProfileAdrenocortex Stress Profile

- Case 3 – - Case 3 – Cortisol Normal, Glucose High Cortisol Normal, Glucose High

Glucometer for Fasting Blood Glucose over 2 ½ monthsGlucometer for Fasting Blood Glucose over 2 ½ months

Best predictor for elevated fasting BG in this case: Inadequate Sleep and 2-3 consecutive work days

4 months, 1 year, 2 years out

Glucometer with “lifestyle diary” as Biofeedback

Case 3: Treatment PlanCase 3: Treatment Plan

Promote Promote adequate rest, Tai Chi, yoga, adequate rest, Tai Chi, yoga, meditation, exercise, counseling referralmeditation, exercise, counseling referral

Acupuncture weekly x 5-8 weeksAcupuncture weekly x 5-8 weeks Alternate Liver Qi movement, Kidney TonificationAlternate Liver Qi movement, Kidney Tonification

Chinese herbs for Chinese herbs for Kidney Yang DeficiencyKidney Yang Deficiency Dynamic Warrior 60 drops/day in AMDynamic Warrior 60 drops/day in AM Warmth Warmth

• Keep warm while exercisingKeep warm while exercising• Eat warming foods (teas, garlic, ginger, steamed vegetables Eat warming foods (teas, garlic, ginger, steamed vegetables

vs. raw)vs. raw)• Avoid cold foods (ice, cool liquids, minimize raw veg)Avoid cold foods (ice, cool liquids, minimize raw veg)

Case 4: Case 4: Perimenopausal AnovulationPerimenopausal Anovulation

42 yo female, normal BMI 24, exercises, fit42 yo female, normal BMI 24, exercises, fit Mild autoimmuneMild autoimmune hypothryoidism hypothryoidism 2005 2005 History suggestive of History suggestive of mild Adrenal stressmild Adrenal stress

4/2010 low secretory IgA, salivary cortisol mildly low in AM (rest 4/2010 low secretory IgA, salivary cortisol mildly low in AM (rest of day normal). Normal fasting insulin and 17-OH progesteroneof day normal). Normal fasting insulin and 17-OH progesterone

• Secretory IgASecretory IgA low levels strongly correlate with daily stress, loss of low levels strongly correlate with daily stress, loss of sense of humor, negative emotions, anger/irritabilitysense of humor, negative emotions, anger/irritability

Martin RA. Int J Psychiatry Med 1998;18:93-105. Rein G. J Adv Med 1995;8:87-105Martin RA. Int J Psychiatry Med 1998;18:93-105. Rein G. J Adv Med 1995;8:87-105

Fatigue responsive to adrenal support supplements in Fatigue responsive to adrenal support supplements in Summer 2010, but Summer 2010, but increased androgenic effect (mild increased androgenic effect (mild facial hair) - facial hair) - Supplements stopped 9/2010Supplements stopped 9/2010

Fatigue partially returned, then better with change from Fatigue partially returned, then better with change from sustained release T3/T4 to Armour Thyroid (low dose 15mg)sustained release T3/T4 to Armour Thyroid (low dose 15mg)

Case 4: Case 4: Perimenopausal AnovulationPerimenopausal Anovulation

Missed menstrual period 9/2010 Missed menstrual period 9/2010 Self-corrected – menstruation 10/2010Self-corrected – menstruation 10/2010 Single ovarian cyst found on ultrasound 10/2010 (not Single ovarian cyst found on ultrasound 10/2010 (not

polycystic)polycystic)

Spring 2011 - Missed menstrual period 60+ daysSpring 2011 - Missed menstrual period 60+ days Abdominal bloating/discomfort, fatigue, hot Abdominal bloating/discomfort, fatigue, hot

flashesflashes Family history of early menopauseFamily history of early menopause Question:Question: Is this perimenopause? Is thyroid Is this perimenopause? Is thyroid

dose correct? Time for hormones? Which?dose correct? Time for hormones? Which?

Urine Pregnancy NegativeUrine Pregnancy NegativeThyroid normalThyroid normal TSH 1.97, FT4 0.93, FT3 2.9TSH 1.97, FT4 0.93, FT3 2.9

Luteinizing HormoneLuteinizing Hormone 55.9 u/L 55.9 u/L (0.8-15.5) (0.8-15.5)

Follicle Stim HormFollicle Stim Horm 30.7 u/L 30.7 u/L (1.4-9.6) (1.4-9.6)

ProgesteroneProgesterone 1.5 ng/ml 1.5 ng/ml (1.4-16.6) (1.4-16.6) 1.5mcg/L1.5mcg/L

Estradiol 129 pg/ml (19-157)Estradiol 129 pg/ml (19-157) 0.129mcg/L0.129mcg/L

Because FSH is only 30 and is Because FSH is only 30 and is about half LH, about half LH, this is not this is not menopause yetmenopause yet (would be very (would be very high FSH)high FSH)

With Progesterone very low, With Progesterone very low, Estradiol modest, and LH high, Estradiol modest, and LH high, this is “anovulation”.this is “anovulation”.

Treatment: Progesterone x 7-10 dTreatment: Progesterone x 7-10 d

Ovulation triggered by LH Surge. If Ovulation triggered by LH Surge. If this is not high enough or is this is not high enough or is gradual or poorly timed, then gradual or poorly timed, then ovulation cannot occur. ovulation cannot occur. Can Can stress play a role?stress play a role?

Hypothalamus - Pituitary – OvaryHypothalamus - Pituitary – Ovary((Stress and the “LH Surge”)Stress and the “LH Surge”)

Ovulation requires correct timing and level of Ovulation requires correct timing and level of Luteinizing Hormone (from pituitary)Luteinizing Hormone (from pituitary) ““LH Surge”LH Surge” Pulsing Pulsing too late, too slowly, or ill timedtoo late, too slowly, or ill timed – no ovulation – no ovulation No ovulationNo ovulation > no corpus luteum > > no corpus luteum > low progesteronelow progesterone

LH Surge requires very specific pulsations of LH Surge requires very specific pulsations of Gonadotropin Releasing Hormone by the Gonadotropin Releasing Hormone by the hypothalamushypothalamus

Can stress influence LH surge?Can stress influence LH surge? Could influencing any stress effect help alleviate Could influencing any stress effect help alleviate

perimenopausal symptoms?perimenopausal symptoms?

Stress and AnovulationStress and Anovulation Administering Corticotropin Releasing Hormone (CRH) inhibits Administering Corticotropin Releasing Hormone (CRH) inhibits

release of Gonadotropin Releasing Hormone (GnRH) at the release of Gonadotropin Releasing Hormone (GnRH) at the HypothalamusHypothalamus

Stress causes ineffective pulsation of the “LH Surge”Stress causes ineffective pulsation of the “LH Surge” Hypothalamic amenorrheaHypothalamic amenorrhea

Stress-induced loss of periods Stress-induced loss of periods • Extensive exercise in young athletes with low body fatExtensive exercise in young athletes with low body fat

High cortisol, High ACTHHigh cortisol, High ACTH• Consistent with chronic stress responseConsistent with chronic stress response

Low LH, FSH, estradiol, allopregnanoloneLow LH, FSH, estradiol, allopregnanolone• Don’t have periods and don’t have enough estrogen to build liningDon’t have periods and don’t have enough estrogen to build lining

Much less responsive to CRH given experimentally and already prone to Much less responsive to CRH given experimentally and already prone to lower CRH due to persistently high cortisol (stress)lower CRH due to persistently high cortisol (stress)

Meczekalski B et al. European Journal of Endocrinology 2000;142:280–285Meczekalski B et al. European Journal of Endocrinology 2000;142:280–285

East German war refugees low cortisol, high LH compared to normal East German war refugees low cortisol, high LH compared to normal

Bauer M et al. Psychiatry Research 1993;5 I:75435Bauer M et al. Psychiatry Research 1993;5 I:75435

Stress-induced high cortisol, high ACTH, and high CRH all cause Stress-induced high cortisol, high ACTH, and high CRH all cause pituitary to release a weak LH surge in sheep, cowspituitary to release a weak LH surge in sheep, cows

Breen KM et al. Endocrinology 148(4):1882–Breen KM et al. Endocrinology 148(4):1882–18901890

Stoebel DP et al. J Dairy Sci 1982;65:1016-1024Stoebel DP et al. J Dairy Sci 1982;65:1016-1024

Stress and PerimenopauseStress and Perimenopause Can stress influence LH surge?Can stress influence LH surge?

YesYes Is it possible to reverse the chronic stress Is it possible to reverse the chronic stress

response and normalize cortisol and CRH?response and normalize cortisol and CRH? YesYes

Could influencing any stress effect help alleviate Could influencing any stress effect help alleviate perimenopausal symptoms?perimenopausal symptoms? Probably, and with other positive health benefitsProbably, and with other positive health benefits

Other considerationsOther considerations Luteal phase progesterone supplementation to Luteal phase progesterone supplementation to

facilitate menstruationfacilitate menstruation Due to development of facial hair (androgen effect)Due to development of facial hair (androgen effect)

• Adaptogens instead of glandulars, pregnenolone, DHEAAdaptogens instead of glandulars, pregnenolone, DHEA• **Elevated LH also increases androgen production**Elevated LH also increases androgen production

Case 4 - Treatment PlanCase 4 - Treatment Plan Induce menses with “progesterone withdrawal” Induce menses with “progesterone withdrawal”

((7-10 days progesterone7-10 days progesterone – period 2 days later) – period 2 days later) Self-examine lifestyleSelf-examine lifestyle

Adequate sleep (use relaxants if needed), negative Adequate sleep (use relaxants if needed), negative vs. positive emotions, regular moving meditation (Tai vs. positive emotions, regular moving meditation (Tai Chi or yoga), B-vitamins, fish oil, magnesium, Chi or yoga), B-vitamins, fish oil, magnesium, consider adaptogens, acupunctureconsider adaptogens, acupuncture

Consider hormones Consider hormones (Testing is useful)(Testing is useful) Test menstrual cycle hormone levelsTest menstrual cycle hormone levels (3 day interval) (3 day interval) Likely to benefit from additional bioidentical Likely to benefit from additional bioidentical

progesteroneprogesterone• Oral if planning to use salivary sampling Oral if planning to use salivary sampling (topical hormones (topical hormones

concentrate in saliva, making followup salivary test useless)concentrate in saliva, making followup salivary test useless) Birth control pill would help but not likely necessary Birth control pill would help but not likely necessary

• Avoid blood clot risk by avoiding estrogens if not indicatedAvoid blood clot risk by avoiding estrogens if not indicated

Lumpkin M. The Hypothyalamic Pituitary Adrenal Axis. Textbook of Functional Medicine. Ed. Jones D. Institute for Functional Medicine. 2005

Polycystic Ovary SyndromePolycystic Ovary Syndrome

SupplementsSupplementsCarrot or Stick? Depends on Use.Carrot or Stick? Depends on Use.

PerspectivePerspective There are There are very few good human studiesvery few good human studies on the on the

use of supplements for fatigue/stressuse of supplements for fatigue/stress There are There are NO long-termNO long-term supplement studies in supplement studies in

fatiguefatigue There are There are numerous studiesnumerous studies on Tai Chi, Yoga, on Tai Chi, Yoga,

Meditation, Exercise, Psychotherapy, SleepMeditation, Exercise, Psychotherapy, Sleep I prescribe supplements with the intention to use I prescribe supplements with the intention to use

them for them for 2-6 months2-6 months Goal: Help restore improved function and less fatigue Goal: Help restore improved function and less fatigue

in order to begin and maintain lifestyle changesin order to begin and maintain lifestyle changes that that are critical to reversing the HPA axis dysfunctionare critical to reversing the HPA axis dysfunction

Primarily based on clinical experience, some Primarily based on clinical experience, some mechanism researchmechanism research

Chronic Fatigue SyndromeChronic Fatigue Syndrome - treatment review - - treatment review -

Chambers D et al. Chambers D et al. J R Soc MedJ R Soc Med. 2006;99:506-520. 2006;99:506-520 Meta analysis reviewed 10,768 publications published on Meta analysis reviewed 10,768 publications published on

interventions for chronic fatigue syndrome and selected interventions for chronic fatigue syndrome and selected 70 that met the selection criteria70 that met the selection criteria

Graded evidence and success of Graded evidence and success of several treatments in orderseveral treatments in order

1.Cognitive Behavioral Therapy1.Cognitive Behavioral Therapy

2. Graded exercise program2. Graded exercise program

3. Inosine pranobex3. Inosine pranobex

4. Low dose hydrocortisone4. Low dose hydrocortisone

Others deserving mentionOthers deserving mention

DHEA DHEA

Acetyl-L-carnitine and propionyl-Acetyl-L-carnitine and propionyl-L-carnitineL-carnitine

EPA-DHA (fish oil)EPA-DHA (fish oil)

MagnesiumMagnesium

Supplement CategoriesSupplement Categories

Adrenal AdaptogensAdrenal Adaptogens NutrientsNutrients

B-vitaminsB-vitamins MagnesiumMagnesium EPA-DHA (fish oil)EPA-DHA (fish oil) CollagenCollagen

RelaxantsRelaxants HormonesHormones GlandularsGlandulars

Adrenal AdaptogensAdrenal Adaptogens

Term coined by Russian Lazarev in 1947 and Term coined by Russian Lazarev in 1947 and modified by Brekhman in 1960smodified by Brekhman in 1960s 1)1) Harmless to host Harmless to host 2)2) Nonspecific, general effect Nonspecific, general effect 3)3) Increases resistance to stressors (physical, Increases resistance to stressors (physical,

chemical or biological)chemical or biological) 4)4) Acts as stabilizer/normalizer Acts as stabilizer/normalizer

ExamplesExamples Rhodiola, Panax ginseng, american ginseng, Rhodiola, Panax ginseng, american ginseng,

ashwaghanda, holy basilashwaghanda, holy basil

Adaptogens - RhodiolaAdaptogens - Rhodiola

Slows degradation of serotonin, dopamine, NESlows degradation of serotonin, dopamine, NE Prevent catecholamine release & activity in heart musclePrevent catecholamine release & activity in heart muscle Prevent catecholamine depletion in adrenalPrevent catecholamine depletion in adrenal

Stancheva SL. Med Physiol 1987;40:85-87Stancheva SL. Med Physiol 1987;40:85-87

Maslova LV et al. Eksp Klin Farmakol 1994;57:61-63Maslova LV et al. Eksp Klin Farmakol 1994;57:61-63

60 subjects with fatigue randomized; rhodiola vs placebo60 subjects with fatigue randomized; rhodiola vs placebo Improved concentrationImproved concentration, , decreased stress-related fatigue,decreased stress-related fatigue,

improved cortisol improved cortisol Olsson EM et al. Planta Med 2009;75:105-112Olsson EM et al. Planta Med 2009;75:105-112

Anxiety improved in RCT of rhodiola use Anxiety improved in RCT of rhodiola use Bystritsky A et al. J Altern Complement Med 2008;14:175-180Bystritsky A et al. J Altern Complement Med 2008;14:175-180

PhysiciansPhysicians in residency (sleep deprivation, night duty) in residency (sleep deprivation, night duty) Reduced fatigue, improved mental performanceReduced fatigue, improved mental performance

Darbinyan V et al. Phyotmedicine 2000;7:365-71Darbinyan V et al. Phyotmedicine 2000;7:365-71

Other AdaptogensOther Adaptogens Ashwagandha Ashwagandha (Ayruvedic Medicine)(Ayruvedic Medicine)

Animal studies show Animal studies show anti-stress, anti-depressant, anti-stress, anti-depressant, anxiolytic, anti-inflammatory, antioxidant, immune anxiolytic, anti-inflammatory, antioxidant, immune function improvement effectsfunction improvement effects

No large human studiesNo large human studies Does not cause high blood pressure, water retention Does not cause high blood pressure, water retention

or insomnia sometimes seen in prolonged high dose or insomnia sometimes seen in prolonged high dose ginseng useginseng use

Holy Basil Holy Basil (Ayruvedic Medicine)(Ayruvedic Medicine) Reduces blood glucoseReduces blood glucose in clinical trial of Type 2 in clinical trial of Type 2

Diabetics Diabetics Animal studies: Animal studies: Stabilizes response to stress, immune Stabilizes response to stress, immune

modulation, liver protective, reduces stomach ulcersmodulation, liver protective, reduces stomach ulcers

Other AdaptogensOther Adaptogens Ginseng Ginseng (Panax, American, Siberian)(Panax, American, Siberian) (Chinese Med)(Chinese Med)

Animal research suggests that the ginsengs produce Animal research suggests that the ginsengs produce stress modulation effects opposite the current cortisol stress modulation effects opposite the current cortisol statusstatus

• Low cortisol – HPA-axis stimulationLow cortisol – HPA-axis stimulation• High cortisol – HPA-axis relaxationHigh cortisol – HPA-axis relaxation

I recommend Panax or American but not Siberian (too I recommend Panax or American but not Siberian (too excitatory/warm)excitatory/warm)

Gaffney BT et al. Life Sci Gaffney BT et al. Life Sci

2001;70:431-4422001;70:431-442

Cordyceps Cordyceps (Chinese Medicine)(Chinese Medicine) Extensively used in Chinese Medicine for Extensively used in Chinese Medicine for

fatigue/vitality, immune dysfunction, and asthma or fatigue/vitality, immune dysfunction, and asthma or other causes of lung dysfunctionother causes of lung dysfunction

Nutrients: Adrenal, CNS and GINutrients: Adrenal, CNS and GI

B vitamins and MagnesiumB vitamins and Magnesium• Important Important co-factors for many reactions in synthesis of co-factors for many reactions in synthesis of

neurotransmittersneurotransmitters. Well documented calming qualities.. Well documented calming qualities.

EPA-DHA (fish oil)EPA-DHA (fish oil) Reduces inflammation, depression, improves lean Reduces inflammation, depression, improves lean

muscle massmuscle mass, lowers epinephrine and norepinephrine , lowers epinephrine and norepinephrine release in stress responserelease in stress response, , lower all-cause mortalitylower all-cause mortality

Chromium – insulin sensitivity, depression, lipidsChromium – insulin sensitivity, depression, lipids Collagen – chicken sternum – for poor Collagen – chicken sternum – for poor

connective tissue in setting of fatigueconnective tissue in setting of fatigue GI – probiotics, glutagenicsGI – probiotics, glutagenics

B-vitaminsB-vitamins B1 – RiboflavinB1 – Riboflavin

Reduces post-operative stress responseReduces post-operative stress response 120mg injected daily for several days pre-surgery 120mg injected daily for several days pre-surgery

reduced cortisol spike during and immediately reduced cortisol spike during and immediately following surgeryfollowing surgery

Continued use for days prevented usual post-Continued use for days prevented usual post-operative rebound cortisol dropoperative rebound cortisol drop

Vinowgradov VV et al. Probl Endokrinol Vinowgradov VV et al. Probl Endokrinol 1981;27:11-161981;27:11-16

B3 – NiacinamideB3 – Niacinamide High doseHigh dose (used for lipid treatment) (used for lipid treatment) increases REMincreases REM

sleep in normal sleepers, and sleep in normal sleepers, and helpful for insomniahelpful for insomnia Mechanism:Mechanism: TryptophanTryptophan levels likely increased levels likely increased

• Negative feedback on tryptophan pyrrolase (trypt > niacin)Negative feedback on tryptophan pyrrolase (trypt > niacin)• Pushes tryptophan into making 5HTP and then to serotoninPushes tryptophan into making 5HTP and then to serotonin• Vitamin B6 is important co-factorVitamin B6 is important co-factor

Robinson CR et al. Biol Psyhiatry 1977;12:139-43Robinson CR et al. Biol Psyhiatry 1977;12:139-43

B-vitaminsB-vitamins B5 Pantothenic AcidB5 Pantothenic Acid

Enhances function of adrenal cortexEnhances function of adrenal cortex Also down-regulates adrenal response in times of high stress Also down-regulates adrenal response in times of high stress

• Blunts response to infused ACTHBlunts response to infused ACTH• Adrenal response to Vit B5 depends on current adrenal functionAdrenal response to Vit B5 depends on current adrenal function

B6 Pyridoxal-5-Phosphate B6 Pyridoxal-5-Phosphate (P5P – active form of Vit B6)(P5P – active form of Vit B6) Essential cofactor for synthesis of Essential cofactor for synthesis of serotonin, dopamine and serotonin, dopamine and

GABAGABA Conversion of tryptophan to 5HTP is the “rate-limiting step for Conversion of tryptophan to 5HTP is the “rate-limiting step for

the creation of serotoninthe creation of serotonin• Inhibited by stress, P5P deficiency, insulin resistance, Mag defInhibited by stress, P5P deficiency, insulin resistance, Mag def

B12 MethylcobalaminB12 Methylcobalamin Combines with bright light exposure to Combines with bright light exposure to reset circadian cortisol reset circadian cortisol

rhythmrhythm (up in AM, low in PM) (up in AM, low in PM) FolateFolate

Required for synthesis of BH4 (tetrahydrobiopterin) which is Required for synthesis of BH4 (tetrahydrobiopterin) which is essential for creation of serotonin, dopamine, epi, & NEessential for creation of serotonin, dopamine, epi, & NE

RelaxantsRelaxants L-TheanineL-Theanine (Green Tea is common source – blunts caffeine effect)(Green Tea is common source – blunts caffeine effect)

Increases serotonin, dopamine, glycineIncreases serotonin, dopamine, glycine Increases alpha-wave activity in brain Increases alpha-wave activity in brain

• Calming, more alert, lower pulse rate with stressorsCalming, more alert, lower pulse rate with stressorsYokogoshi H. Neurochem Res 1998;23:667-73. Yamada T. Amino Acids 2009;36:21-37Yokogoshi H. Neurochem Res 1998;23:667-73. Yamada T. Amino Acids 2009;36:21-37Ito K. Nippon Nogeikagaku Kaishi 1998;72:153-7 Kimura K. Biol Psychol 2007;74:39-45Ito K. Nippon Nogeikagaku Kaishi 1998;72:153-7 Kimura K. Biol Psychol 2007;74:39-45

GABAGABA – – gamma-Aminobutyric acid – inhibitory gamma-Aminobutyric acid – inhibitory neurotransmitterneurotransmitter GABA receptor bound by benzodiazepines and sleep GABA receptor bound by benzodiazepines and sleep

aids (calming effect)aids (calming effect) Reduces stress response, anxiety/panic, insomniaReduces stress response, anxiety/panic, insomnia Abdou AM Biofactors Abdou AM Biofactors

2006;26:201-82006;26:201-8 Green ML Biofeedback Self Regul 1988;13:187-99Green ML Biofeedback Self Regul 1988;13:187-99

RelaxantsRelaxants L-tryptophan / 5-HTP L-tryptophan / 5-HTP (5-hydroxytryptophan)(5-hydroxytryptophan)

Precursor to serotonin. As effective as tricyclics for Precursor to serotonin. As effective as tricyclics for depressiondepression. . Improves Improves PremenstrualPremenstrual mood swings. mood swings.

Improves Improves sleepsleep onset and quality. onset and quality. Richard DM. Int J Tryptophan Res. 2009 March 23; 2: 45–60Richard DM. Int J Tryptophan Res. 2009 March 23; 2: 45–60

Does not limit cognitive performance or inhibit arousal from sleepDoes not limit cognitive performance or inhibit arousal from sleep Lieberman HR. Am J Clin Nutr 1985;42:366-70Lieberman HR. Am J Clin Nutr 1985;42:366-70

5HTP 2mg/kg effective for childhood 5HTP 2mg/kg effective for childhood night terrorsnight terrors Bruni O et al. Eur J Pediatr Bruni O et al. Eur J Pediatr

2004;163:402-72004;163:402-7

Bacopa Bacopa (Ayruvedic Medicine)(Ayruvedic Medicine) Effective for anxiety and cognitive function in randomized trialsEffective for anxiety and cognitive function in randomized trials

Singh RH et al. J Res Ayru Singh RH et al. J Res Ayru Siddha1980;1:133-148Siddha1980;1:133-148

Stough C. Stough C. Psychopharmacology 2001;156:481-84Psychopharmacology 2001;156:481-84

Calabrese C. Altern Complement Med 2008;14:707-13Calabrese C. Altern Complement Med 2008;14:707-13

RelaxantsRelaxants

L-TyrosineL-Tyrosine Precursor to catecholamines (dopamine, epinephrine, Precursor to catecholamines (dopamine, epinephrine,

norepinephrine)norepinephrine) Helps prevent stress-induced depletion of Helps prevent stress-induced depletion of

catecholaminescatecholamines Improved performance in stressful situationsImproved performance in stressful situations

MelatoninMelatonin Well documented efficacy for insomnia and jet lagWell documented efficacy for insomnia and jet lag Can cause Can cause dream disturbed sleepdream disturbed sleep Can inhibit arousal from sleep (Can inhibit arousal from sleep (sleep hangover effectsleep hangover effect))

HormonesHormones A word to the wise….A word to the wise….

Use as little dose (per day and over time) as Use as little dose (per day and over time) as necessarynecessary Avoid very long periods (>6 months) if possibleAvoid very long periods (>6 months) if possible Accept the risks if outweighed by benefitsAccept the risks if outweighed by benefits Try intermittent downward tapers of hormonesTry intermittent downward tapers of hormones

If low hormones are replaced, the rest of the If low hormones are replaced, the rest of the Endocrine System will respond/adjustEndocrine System will respond/adjust Very complex systemVery complex system Screen for Screen for prostate/breast cancerprostate/breast cancer Remember the Carrot/Whip metaphor Remember the Carrot/Whip metaphor

Glandular HormonesGlandular Hormones Animal endocrine organs purified/extracted/driedAnimal endocrine organs purified/extracted/dried Common example of standardized glandular is Armour ThyroidCommon example of standardized glandular is Armour Thyroid Literature review dominated by 1930-1940s – no current scientific Literature review dominated by 1930-1940s – no current scientific

articles on medicinal use of adrenal glandulararticles on medicinal use of adrenal glandular Adrenal cortical extractAdrenal cortical extract

Injected into children, studied blood chemistry and immunological Injected into children, studied blood chemistry and immunological effectseffects

Increased cholesterol, tendency toward lower glucose level.Increased cholesterol, tendency toward lower glucose level. Normal CBC, sedimentation rate, total protein and pertussis titres – no Normal CBC, sedimentation rate, total protein and pertussis titres – no

changechange Kelley VC, Adams JM. J Peds 1948;32(3):Kelley VC, Adams JM. J Peds 1948;32(3):282-287282-287

My anecdotal clinical experienceMy anecdotal clinical experience Equivalent to a low dose of cortisol, Equivalent to a low dose of cortisol, frequently helpful for fatiguefrequently helpful for fatigue Adverse:Adverse: Can cause Can cause over-stimulation of the HPA Axisover-stimulation of the HPA Axis – increased – increased

cortisol, insomnia, high blood pressure, “wired” effectcortisol, insomnia, high blood pressure, “wired” effect Two concerns:Two concerns: 1) prolonged use (>6 months) 2) contaminants from 1) prolonged use (>6 months) 2) contaminants from

food chainfood chain

HormonesHormones

PregnenolonePregnenolone Modulates NMDA and GABA receptorsModulates NMDA and GABA receptors Use – in setting of low cortisol with fatigueUse – in setting of low cortisol with fatigue

• Short term 2-3 months for symptomatic relief. Short term 2-3 months for symptomatic relief. Increase exercise, rest, relaxation, adaptogensIncrease exercise, rest, relaxation, adaptogens

AdverseAdverse – increased androgens (hair growth, – increased androgens (hair growth, acne, irritability), insomnia, palpitationsacne, irritability), insomnia, palpitations

ProgesteroneProgesterone – previously discussed – previously discussed No long-term studiesNo long-term studies

Hormones - DHEAHormones - DHEA Effective in major and non-major depression in men and Effective in major and non-major depression in men and

women women Wolkowitz OM et al. Am J Wolkowitz OM et al. Am J

Psychiatry.1999;156:646-649Psychiatry.1999;156:646-649 Rabkin JG. Am J Psychiatry. 1996;163:59-66 Rabkin JG. Am J Psychiatry. 1996;163:59-66

Schmidt. Arch Gen Psychiatry. 2005;62:154-Schmidt. Arch Gen Psychiatry. 2005;62:154-162162

ImprovesImproves concentration, libido and fatigue in small concentration, libido and fatigue in small studies of Chronic Fatigue Syndrome and Lupusstudies of Chronic Fatigue Syndrome and Lupus

Adverse effectsAdverse effects Facial hair, acne, irritability, elevated BP, insomnia, reduces Facial hair, acne, irritability, elevated BP, insomnia, reduces

efficacy of tamoxifen if DHEA-S levels efficacy of tamoxifen if DHEA-S levels >>9090 Theoretical fear of amplifying breast/ovarian/prostate cancer due Theoretical fear of amplifying breast/ovarian/prostate cancer due

to conversion to estrogen and testosterone – to conversion to estrogen and testosterone – clinical exam and clinical exam and lab screeninglab screening

No long term studies to establish safety of long term useNo long term studies to establish safety of long term use

Hormones - CortisolHormones - Cortisol

5-10mg/day for 1 month effective for CFS 5-10mg/day for 1 month effective for CFS without psychological diagnosis without psychological diagnosis Physiologic dosing equivalentPhysiologic dosing equivalent Reduced fatigue without affecting endogenous Reduced fatigue without affecting endogenous

adrenal functionadrenal function Cleare AJ et al. Lancet 1999; 353(9151):455 – 458Cleare AJ et al. Lancet 1999; 353(9151):455 – 458

Well established in Adrenal InsufficiencyWell established in Adrenal Insufficiency Failure to double cortisol level with ACTH 250mcgFailure to double cortisol level with ACTH 250mcg

No long-term studies other than Adren InsuffNo long-term studies other than Adren Insuff

SupplementsSupplements

I select supplements based either on I select supplements based either on testing or on questionnaire-based protocoltesting or on questionnaire-based protocol Adrenocortex Stress ProfileAdrenocortex Stress Profile

• Salivary Cortisol at 7AM, 10AM, 4PM, 11PMSalivary Cortisol at 7AM, 10AM, 4PM, 11PM• Salivary DHEA at 7AMSalivary DHEA at 7AM• Some tests include 17-OH ProgesteroneSome tests include 17-OH Progesterone

More objective rationale for use of progesterone, More objective rationale for use of progesterone, however clinical observation is as usefulhowever clinical observation is as useful

Thyroid studies, CBC, Chem 14Thyroid studies, CBC, Chem 14• Make sure no thyroid, hematologic, kidney, liver dzMake sure no thyroid, hematologic, kidney, liver dz

Metagenics Stress IdentiT protocolMetagenics Stress IdentiT protocol

SummarySummary Chronic, persistent stress is harmful & feels badChronic, persistent stress is harmful & feels bad Restful, uninterrupted Restful, uninterrupted sleep is essentialsleep is essential Loosen Attachment to Destructive EmotionsLoosen Attachment to Destructive Emotions

Anger, worry, anxiety, irritabilityAnger, worry, anxiety, irritability Psychological Psychological counseling importantcounseling important

Promote positive outlookPromote positive outlook Tai Chi, Yoga, Moderate Exercise, MeditationTai Chi, Yoga, Moderate Exercise, Meditation Supplements can play a role for Supplements can play a role for short termshort term

2-6 months 2-6 months Not likely good to use on a chronic, continuous basisNot likely good to use on a chronic, continuous basis Used to improve quality of life and well-being Used to improve quality of life and well-being long long

enough to take advantage of lifestyle changesenough to take advantage of lifestyle changes

The Five AgreementsThe Five Agreementsby Don Miguel Ruizby Don Miguel Ruiz

1. Be Impeccable With Your Word. 1. Be Impeccable With Your Word. 2. Don't Take Anything Personally. 2. Don't Take Anything Personally.

3. Don't Make Assumptions. 3. Don't Make Assumptions. 4. Always Do Your Best.4. Always Do Your Best.

5. Be Skeptical, But Learn to Listen.5. Be Skeptical, But Learn to Listen.

Stress, Fatigue Stress, Fatigue and and

The AdrenalsThe Adrenals

Tom Archie, MDTom Archie, MD

St Luke’s Wood River St Luke’s Wood River Family MedicineFamily Medicine

www.drtomsalchemy.com

stress, fatigue and the adrenals tom archie, md tom archie, md st lukes wood river family medicine...

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