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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
Hypothalamic Pituitary Adrenal AxisHypothalamic Pituitary Adrenal Axis
Cerebral Cortex
Hypothalamus
Pituitary
Adrenal sits on Kidney
Hypothalamic Pituitary Adrenal AxisHypothalamic Pituitary Adrenal Axis
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
Theory of Progesterone StealTheory of Progesterone Steal(aka: Pregnenolone Steal - or - Estrogen Dominance)(aka: Pregnenolone Steal - or - Estrogen Dominance)
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?
Theory of Progesterone StealTheory of Progesterone Steal(aka: Pregnenolone Steal - or - Estrogen Dominance)(aka: Pregnenolone Steal - or - Estrogen Dominance)
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
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
Chinese Medicine and AdrenalsChinese Medicine and Adrenals
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
Five Element CorrespondencesFive Element Correspondences
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
Five Element CorrespondencesFive Element Correspondences
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
Five Element CorrespondencesFive Element Correspondences
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