nm w i

Women’s Functional and Integrative Medicine Professional Training

Supplements for HPA Axis Support: Nutrients, Nervines, and Adaptogens Part 2: The Adaptogens and Other Support

M o d u l e 7

Commonly Used AdaptogensHerbal Action Botanical Name Common Name

Adaptogens EleutherococcussenticosusPanax ginsengPanax quinquefoliumRhodiola roseaSchizandra chinensisWithania somniferaGanoderma lucidumCordyceps sinensisGlycyrrhiza glabra

Eleuthero

GinsengAmerican ginsengRhodiolaSchizandraAshwagandhaReishiCordycepsLicorice

Spectrum of Adaptogens

Ashwagandha, Mushrooms (i.e., Adrena Soothe)

Maca, Schizandra, Holy basil, Eleuthero

(i.e., Adrena Nourish)

Rhodiola American ginseng, Panax ginseng

(i.e., Adrena Uplift)

Ashwagandha (Withania somnifera)Traditional Use• Rasayana herb in Ayurveda• Increased vitality• Longevity• Prevent disease• Relieve fatigue, nervous exhaustion,

anxiety• Insomnia• Memory-enhancing• Retard “brain aging”• Regenerate neural tissue• Arthritis• GI disorders

Ashwagandha• Anxiety, stress response,

insomnia

• Arthritis

• Cancer

• Cardiovascular effects• Debility, Stamina

• Epilepsy

• Growth and development• Immune system/ Infection

• Inflammation/ Oxidation

• Memory

• Morphine withdrawal

• Muscle spasm, pain

• Sedation

• Thyroid stimulant

Ashwagandha Actions

• Withanolides structurally similar to ginsenosides.

• Animal research suggests analgesic, antipyretic, anxiolytic, immunomodulatory, sedative, hypotensive, anti-inflammatory, and antioxidant effects.

• Stimulates respiratory function

• Stimulate thyroid hormone synthesis and/or secretion.

• Suppresses stress-induced increases of dopamine receptors in the corpus striatum.

• Reduces stress-induced increases of corticosterone, BUN, and lactic acid.

Ashwagandha cont’d.• Anxiolytic effects, possibly as a GABA mimetic agent. Possible anticonvulsant

activity, by binding to the GABA receptor.

• Mobilization of macrophages, phagocytosis, and lysosomal enzymes.

• Reduced cyclophosphamide-induced immunosuppression and leukopenia; seems to increase bone marrow cell and white blood cell count in radiation-treated.

• Rich in iron, which may help reduce anemia and improve overall health & functioning. 2 Indian studies:

• 58 child given 2 g/day or a placebo for 60 days. Significant increase in hemoglobin and serum albumin and no adverse effects.

• 101 adults given 3 g/day or placebo for a year. Increase in hemoglobin and RBC counts, improved libido & sex performance.

Ashwagandha Clinical StudiesAnxietyRCT studying ashwagandha in a combination naturopathic care model for anxiety treatment (N=81) in subjects with moderate-to-severe anxiety lasting six weeks or longer. •Treatment was composed of dietary counseling, deep breathing exercises, a multivitamin,

and ashwagandha root 300mg twice daily (standardized to 1.5% anolides) for 12 weeks vs. control therapy without ashwagandha.

•Beck Anxiety Inventory scores decreased 56.5% from baseline (p

Enhanced Immunity• Combination Ayurvedic herbal tea increased NK cell activity (N=32).

Elettaria cardamomum, Glycyrrhiza glabra, Ocimum sanctum, Withania somnifera, and Zingiber officinale were compared to regular tea in healthy volunteers aged ≥55 years with low baseline NK cell activity and recurring coughs and colds.

• 6mL of ashwagandha root extract with whole milk twice daily for 96 increased CD4, CD8, CD19, CD56, and CD69 receptor cell surface expression and increased CD4 expression on CD3+ T cells after 96 hours. CD56+ NK cells were also activated. (N=5)

Phytother.Res 2010;24(1):129-135.J.Altern.ComplementMed. 2009;15(4):423-430.

Ashwagandha and Thyroid• 1998 mouse study, high dose ashwaganda extract (1.4g/kg/day) was

administered for 20 days. This increased serum T4 and T3 concentrations and reduced hepatic lipid peroxidation (while increasing SOD)

• A year later, the same researchers used a similar dosing regimen and protocol to test a combination of ashwaganda and Bauhinia purpurea bark extract. In this study, Bauhinia significantly increased concentrations of T3 and T4 but ashwaganda only increased T4, and to a lesser degree. Oral administration of either ashwaganda (1.4g/kg/day) or Bauhinia purpurea(2.5mg/kg/day) extract elevated the serum concentrations of T3 and T4 to euthyroid levels in a rodent model of metformin-induced hypothyroidism (using Type II diabetic mice).

The Journal of Pharmacy and Pharmacology, 1998. 50(9), 1065-8. •Journal of Ethnopharmacology, 1999. 67(2), 233-9. Phytotherapy Research. 2009. 23(8), 1140-5. •Journal of Ayurveda and Integrative Medicine, 5(4), 241-5.

J AlternComplement Med. August 22, 2017; [epubahead of print].

Ashwagandha and Thyroid • A surprising observation came out of a 2014 clinical trial testing ashwaganda for

the improvement of cognitive functioning in bipolar disorder. The researchers had seen a case report of ashwaganda-associated thyrotoxicosis4 and tested trial patients for thyroid function. 10 out of the 60 trial patients presented abnormal thyroid function , and all 3 that were treated with ashwaganda demonstrated increases in T4 concentrations from baseline.

• An 8-week study suggested that ASW may increase thyroxine levels, and therefore vigilance regarding hyperthyroidism may be warranted. “Nonetheless, the thyroid enhancing properties of ASW may also represent a clinical opportunity for the treatment of subclinical hypothyroidism”

• In a recent clinical trial, 50 patients with mild hypothyroidism took either 600 mg of ashwagandha or a placebo every day for eight weeks. By the end of the study, the people taking ashwagandha saw their thyroid hormone levels increase by 41%.

Ashwagandha Safety

• Used safely in clinical trials lasting up to 12 weeks.

• Orally, well tolerated at typical doses.

• Large doses may cause GI upset and vomiting secondary to irritation of the mucous membranes.

• While pregnancy abortifacient activity found in some literature is based on erroneous reporting of a single case history, safety during pregnancy is not conclusive though there is evidence of traditional use.

• Theoretical condition or drug interactions: CNS additive effects, antihypertensive effects, thyroid stimulating effects, aggravation of PUD, reduction in blood glucose levels.

Ashwagandha Dosing

• 1 to 6 grams daily of the whole herb in capsule or tea form in 2-3 divided doses

• Standardized extracts can be taken at 500 mg, 2-3 x/day.

• The tea is prepared by boiling ashwagandha roots in water for 15 minutes and cooled. The usual dose is 3 cups daily.

• Tincture or fluid extracts are dosed 2 to 4 mL 3 times per day.

Medicinal Mushrooms• Immunomodulation: Mushrooms

support immune function, and they do so in a way that is normalizing to the immune system as opposed to being a stimulant. You can think of them as immune tonics that are applicable in a wide variety of situations, including-

• Lowered resistance and “catching things” easily

• Chronic or persistent infections

• Certain autoimmune disorders

Mushrooms Alert Innate Immunity• Mushrooms affect immune function because they have compounds that resemble a

microbe.

• Our vigilant immune cells sense this and respond to it by increasing innate immune activity (our front-line defenses). This puts our system on alert and provides a workout for our immune systems, making them stronger over time.

• Many types of mushrooms provide this activity, even common edibles like Shiitake and Oyster mushrooms.

• They help support other areas of the body too, like the nervous system, liver, cardiovascular system, and have actions including: Improved immunocompetenceafter chemo, Anti-inflammatory, Platelet aggregation inhibition, Hepatoprotective

(hepatitis B, C), Antitumor, Hypoglycemic, Cholesterol lowering, Fatigue, insomnia,

restlessness

Reishi (Ganoderma lucidum)• Probably the most well-known medicinal mushroom.

• Its use as a general wellness tonic is evident in some of its other common names, like “Mushroom of Immortality” and “Mushroom of Longevity”.

• It can be used on an acute as well as long-term basis to support immune functioning. T

• This restorative mushroom also helps support the HPA Axis: this as the mushroom to use when you’re stressed out, run down, and getting sick frequently.

• It’s also a fabulous mushroom for allergies and hay fever as it can reduce the histamine response to environmental triggers.

• The doses are on the high end for medicinal mushrooms. It’s suggested to take 5ml of the tincture 3 times daily for active immune boosting, or 2ml twice daily for immune and

adrenal support.

Lion’s Mane (Hericium erinaceus)• Beautiful white mushroom that resembles a white pom pom with elongated

spines.

• Also supports immunity, but Lion’s Mane is really best known for its neurological and mental health benefits.

• It contains compounds that protect and promote growth in neurons. Clinical research with Lion’s Mane has demonstrated efficacy for anxiety, depression, and cognitive function.

• This is a mushroom to consider for overall nervous system health.

• Lion’s Mane mushroom powder is often found as an encapsulated product. Maintenance doses are 1-2g daily, with the therapeutic doses starting at 3g daily.

Maitake (Grifola frondosa)• Prized for its immune supportive properties.

• It contains a compound known as D-fraction that has been heavily researched for cancer treatment.

• Maitake may also help address common cardiovascular risk factors, such as high blood pressure, elevated cholesterol levels, and even blood sugar issues.

• Maitake mushrooms can be incorporated into your diet for year-round immune health.

• Tincture doses are 5ml 3 times daily for active immune boosting, or 2ml twice daily for maintenance.

Reishi Chai TeaTo 1 quart of water, add:

• 2-3 slices of dried Reishi mushrooms (available organically through Mountain Rose Herbs)

• ½ cinnamon stick

• 3 cardamom pods

• 2 cloves

• 1 peppercorn

• Turn heat on medium-high until the tea reaches a boil. Lower heat and simmer for 15-20 minutes. Strain and add milk and sweetener of your choice. You may also add other herbs- I add a pinch of Ashwaganda root for extra adrenal support. Can be stored in the fridge and chilled for an iced version.

Eleuthero (Eleutherococcus senticocus)Traditional Use

• Increased endurance

• Memory improvement

• Immunological enhancement

• Overall well-being

Eleutherococcus (ES)Herbalists Use for:• General weakness and debility• Anorexia• Insomnia/ Dream-disturbed sleep• Immunomodulating• Stress reducing• Performance and energy enhancing• Anabolic• Reduction of serum lipid-peroxide levels and improved lipid metabolism. • Increased T-lymphocyte counts and • Chronic fatigue • Reductions in cardiovascular stress response

A review by Farnsworth et al of Russian clinical trials on more than 2,100 healthy human subjects, ranging in age from 19-72 yo indicates increased ability to accommodate to adverse physical conditions, improvement in mental performance, and enhancement the quality of work under stress.

Stress Health, 2002. 18:11-17Econ Med Plant Res, 1985.1:156-215.

ES Mechanisms of Action• Eleutherosides A through M identified 1954.

• Eleutheroside B (syringin) and eleutheroside E (syringaresinol) used as marker compounds for ES products.

• The eleutherosides include saponins, coumarins, lignans, phenylpropanoids, betulinic acid, vitamin E, and provitamins, i.e., beta-carotene.

• Thought to have antioxidant and possible anticancer effects.

• Some evidence that coniferyl aldehyde protects DNA against UV light damage. • Antiproliferative effect on leukemia cells and appear to potentiate the effect of

antimetabolites such as cytarabine (7525).

• Preliminary evidence that suggests it might act as an antioxidant and prevent damage in ischemic stroke.

J Ethnopharmacol 2000;72:345-93.J Pharm Sci 1984;73:270-2. J Nat Prod 1986;49:293-7.

• Immunostimulatory effects; ES increases lymphocyte counts and phagocyte activity.

• Eleutherosides A through G, particularly eleutheroside G, appear to have hypoglycemic activity. Some research suggests that ES may actually increase postprandial blood glucose levels.

• Some eleutherosides have structural similarities to cardiac glycosides and can interfere with measurement of serum digoxin levels by some assay methods. It is unclear whether ES has any of the pharmacological effects of cardiac glycosides.

• ES root extract seems to inhibit RNA-type viruses including human rhinovirus, respiratory syncytial virus (RSV), and influenza A virus, but has no effect on DNA viruses such as adenovirus or herpes simplex type 1 virus (HSV-1).

Am J Clin Pathol 2003;119:298-303. Antiviral Res 2001;50:223-8.

J Am Coll Nutr 2004;23:248-58.

ES & HSV-2A specific ES extract, standardized to contain eleutheroside 0.3% (Elagen), orally seems to reduce the frequency, severity, and duration of herpes simplex type II infections. • In a double-blind study to examine the effect of ES extract on symptoms of genital herpes in

93 men and women. a pure standardized extract of ES was used. • After 3 months patients using the ES extract reported a reduction in severity, duration, and

frequency of outbreaks compared with placebo.

ES & Common cold• A specific combination product containing ES plus andrographis (Kan Jang, Swedish Herbal

Institute) orally significantly improves symptoms of the common cold when started within 72 hours of symptom onset.

• Some symptoms can improve after 2 days of treatment. It typically takes 4-5 days of treatment before there is maximal symptom relief .

• The combination of ES and andrographis relieves cold symptoms better than Echinacea or placebo in children.

Phytomedicine 2002;9:589-97Phytother Res 2004;18:47-53.

ES & Upper Respiratory InfectionMelchior et al. conducted 2 randomized, double-blind, placebo controlled, parallel-group trials to investigate the effect of Kan Jang® in the treatment of uncomplicated URI. • Forty-six patients in the pilot study and 179 patients in the phase III study completed the

study. • Medication was taken tid for a minimum of 3 days and a maximum of 8 days for the pilot

study, and for 3 days in the phase III study.• Primary outcome measures were related to pain in the muscle, cough, throat symptoms,

headache, nasal symptoms, eye symptoms, and temperature. • The physician's fixed-score diagnosis was based on ear, nose, oral cavity, lymph gland,

tonsil, and eye symptoms. • The total symptom score showed a tendency toward improvement in the pilot study

(p=0.08), while both the total symptom score and total diagnosis score showed highly significant improvement (p≤0.0006 and 0.003, respectively) compared with the placebo group.

• In both studies, throat symptoms showed the most significant improvement.

Phytomedicine. 2000;7(5):341-350.

ES & InfluenzaKulichenko et al. conducted a randomized controlled study comparing Kan Jang® (a combination product containing ES) vs. amantadine in the treatment of influenza. •540 patients enrolled in the first phase of the study; the second phase enrolled 66 patients. •Outcomes were the duration of sick leave and frequency of post-influenza complications. •Kan Jang® contributed to quicker recovery and reduced the risk of post-influenza complications.•Kan Jang® was well tolerated by patients.

ES & General ImmunityBohn et al. conducted a placebo controlled study to examine the effect of a ES extract (Eleu-kokk®) on immune system function in 36 healthy volunteers.•Volunteers received 10mL of an ethanolic extract of ES or placebo (wine) three times daily for four

weeks. •The main endpoint was cellular immune status, as determined by quantitative flow cytometry. •ES use resulted in an increase in the absolute number of immunocompetent cells, mainly T helper

cells. There were also effects on cytotoxic and natural killer cells. •There were no side effects observed over a six-month period.

Arzneimittelforschung. 1987;37(10):1193-1196.Int J AlternComplemMed 1995;13:9-12.J.Herb.Pharmacother. 2003;3(1):77-93

Osteoarthritis/InflammationDouble-blind, randomized, placebo controlled study to determine the effect of anti-inflammatory factor (AIF) on knee osteoarthritis in Korean patients. • AIF is a water-soluble extract of Panax notoginseng, Rehmannia glutinosa, and ES. • Fifty-seven patients with knee OA, from 43 to 73 years of age, who fulfilled the

American College of Rheumatology classification of idiopathic osteoarthritis of knee with radiographic criteria

• Randomized to receive two capsules of 400mg of AIF or similar identical placebo twice daily for six weeks.

• Outcome measures included pain intensity using a visual analog scale, as well as changes in the Korean version of the Western Ontario and McMaster Universities (K-WOMAC) index score.

• Pain was significantly reduced (at visit 2: 54.64 ± 14.72, at visit 4: 37.32 ± 16.58, p

McNaughton et al. compared the effects of ES and Chinese ginseng with placebo on exercise tolerance in a randomized crossover study. • Thirty trained runners were included and assigned to ES (1g daily), Chinese ginseng, or placebo,

for six weeks each. • Major endpoints included VO2max, heart rate recovery, and strength. ES had no effect on

VO2max, heart rate recovery, or grip strength, compared with the placebo. • There was a significant increase in pectoral and quadriceps strength, by 15 and 13%,

respectively.

Asano et al. conducted a single-blind crossover study to examine the effect of ES on physical working capacity in six healthy male athletes.• Subjects belonged to the same baseball team and ate the same food. • No other inclusion or exclusion criteria were provided. Subjects were given 2mL of ES extract

(150mg of dried material) or placebo twice daily for eight consecutive days. • The main endpoints were maximal work on a bicycle ergometer and aerobic capacity. • Total work increased significantly with ES compared with the placebo group (23.3% vs. 7.5%),

as did exhaustion time (16.3% vs. 5.4%). • Maximal oxygen uptake was only increased compared with control (presupplementation). • Limitations to this trial include the single-blind nature of the study and no mention of

randomization.

Planta Med 1986;(3):175-177.Int.Clin.Nutr.Rev. 1989;9:32-35.

Comparison of the effect of ES to a combination ES, Cordyceps, and ginseng on cardiorespiratory fitness during submaximal cycling exercise.•16 healthy male volunteers•Group A (N=8) received 10mL of oral ES preparation (Endurox®)

equivalent to 800mg of ES daily, 30 minutes before breakfast. Group B (N=8) also received the same dose of Endurox®, in addition to 400mg of Cordyceps and 200mg of ginseng liquid extract, in the form of an oral liquid preparation.

•2 week duration of study•Both groups received placebo medication for three days prior to

treatment initiation.•Subjects completed aerobic and anaerobic exercise tests, once after

three days of placebo, and again after two weeks of active treatment. •Outcome measures included heart rate, lactate accumulation, and

respiratory quotient. •The submaximal cycling test started at an initial load of 60W for three

minutes and then increased every three minutes by 30W, up to 210W. •Following ES supplementation, both heart rate and lactate

accumulation decreased (34%, in group A), load increased (12% in group A), VO2 at anaerobic threshold) increased (7%, in group A), and fat metabolism increased (43%).

•ES supplementation alone was more effective than the combination with Cordyceps and ginseng.

Wu, Y. N. X. Q. Wang Y. F. Zhao J. Z. Wang H. J. Chen and H. Z. Effect of Ciwujia (Radix acanthopanacis senticosus) preparation on human stamina. J.Hyg.Res. 1996;25:57-61.

Evidence from a Phase II DB,PC, RCT that ADAPT-232 (containing Rhodiola rosea, Schisandra chinensis, and ES) improved cognitive function in females.• Forty healthy females (20-68 years of age) that reported

living under chronically psychologically stressful conditions participated. The participants were randomized into to receive a single tablet of 270mg of ADAPT-232 (N=20) or a single tablet of placebo (N=20).

• A Stroop color-word test was used to exhaust the volunteers before the assessment of cognitive function of patients. The effects of ADAPT-232 extract were measured prior to treatment and two hours after treatment using the d2 test of attention (d2).

• The subjects in the ADAPT-232 group quickly gained improved attention and increased speed and accuracy during stressful cognitive tasks, in comparison to placebo (p

RCT to examine the effect of ES for chronic fatigue syndrome.• Subjects were required to have substantial fatigue for 6

months or more, with no identifiable cause. • Patients with HTN and certain medications, diseases,

and abnormal laboratory results were excluded • 96 subjects (~ 80% female) were included, and 76

patients completed the study. The remaining patients were lost to follow-up or to side effects, such as nervousness, headache, and breast tenderness.

• Patients were given placebo or four 500mg capsules of ES (Frontier Herbs, Norway, IA) for 2 months.

• Main endpoint: mean change in a fatigue measure, compared with placebo, at one and two months.

• Fatigue was reduced in study subjects overall, with no differences between groups.

• In patients with less severe fatigue, fatigue severity and duration were reduced in those taking ES.

Hartz, A. J., Bentler, S., Noyes, R., Hoehns, J., et al. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol.Med2004;34(1):51-61

Other interesting ES dataNeurocirculatory Hypotension

(i.e., Potts Syndrome, Autonomic Dysfunction)

• Preliminary data suggest that use of ES extract increases systolic and diastolic blood pressure in individuals with neurocirculatoryhypotension.

• Kaloeva examined the efficacy of ES extract on neurocirculatoryhypotension in children aged 7-10 years. Systolic and diastolic blood pressures were increased with treatment.

Farmakol.Toksikol. 1986;49(5):73.

Safety

• According to a review, side effects of ES are considered to be minimal.

• Root extract has been used safely in clinical trials lasting up to 2 months.

• A specific combination product containing ES plus andrographis (Kan Jang, Swedish Herbal Institute) has also been safely used in multiple short-term clinical trials lasting 4-7 days

• One clinical trial used this combination (with andrographis) product in low doses for up to 3 months.

Dosing

• Powder: 400 mg bid-tid

• Tincture (1:4) 60-100 drops 3-4 times daily or a fluid extract (1:1) 20-40 drops three times daily has been use

• Variably standardized to eleutherosides B and E Phytomedicine1997;4:101-4.Phytomedicine1999;6:217-23.Arch Gerontol Geriatr Suppl 2004;9:69-73

ES Safety & Dosing

Rhodiola (Rhodiola rosea)Traditional Use

• “Asthenic” conditions

• Decline in work performance

• Sleep disturbance

• Poor appetite• Irritability

• Sexual dysfunction

• Fatigue subsequent to intense physical or intellectual strain or illness.

• Headache

Krasik E, PetrovaK, RogulinaG, et al. New data on the therapy of asthenic conditions(clinical prospects for the use of Rhodiolaextract). Proceedings of All-Russia Conference: Urgent Problems in Psychopharmacology 1970 May 26-29. Sverdlovsk, Russia: Sverdlovsk Press; 1970.p. 215-7.

Krasik E, MorozovaE, PetrovaK, et al. Therapy of asthenic conditions: clinical perspectives of application of Rhodiola roseaextract. In. Proceedings Modern problems in psycho-pharmacology. Kemerovo-city, Russia: Siberian Branch of Russian Academy of Sciences: 1970.p. 298-330.

RhodiolaThe adaptogenic, cardiopulmonary protective, and central nervous system activities of Rhodiola have been attributed primarily to its ability to influence levels and activity of monoamines and opioid peptides such as beta-endorphins.

• Anxiety (GAD) – increases 5-HT • Stress• Burn out feelings, irritability• Immune support – decrease frequency of colds, infections• Decreased inflammation. i.e. lower CRP• Physical and somatic concerns

Rhodiola (Rhodiola rosea) cont.• CFS, FM

• Antiarrhythmic

• Potentiation of antitumor meds, i.e. cyclophosphamide

• Prevent high altitude sickness

• Work performance

• Sleep difficulties, fatigue

• Poor appetite

• Hypertension

• Headaches

• Erythropoeisis

Rhodiola Systematic ReviewHung et al. conducted a systematic review to evaluate the randomized controlled trials evaluating Rhodiola rosea. • Twelve randomized controlled trials were included, all

of which were placebo controlled trials.• Six trials evaluated rhodiola for exercise

performance, four for mental performance, and two for mental health conditions.

• Significant benefit was noted in eight studies. • Adverse effects were mild and infrequent. • Five of the studies had a Jadad score of 3 or higher,

indicating good quality.

Phytomedicine, 2011. 8(4):235-244.

Rhodiola Actions• Salidroside is thought to be responsible for many of the stimulant or "adaptogenic" effects.

• The adaptogenic, cardiopulmonary protective, and CNS effects attributed to influence on levels and activity of monoamines via reduction of MAO and increasing NTs (i.e., serotonin) and opioid peptides (i.e., beta-endorphins. )

• Appears to have significant CNS activity.

• In animal models, a rhodiola extract containing 3% rosavin and 1% salidroside has antidepressant, anxiolytic, and stimulant effects.

• In animal models, the salidroside constituent also has sedative effects.

• Rhodiola extracts also demonstrate potential for improving learning and memory.

• Rhodiola extracts might also prevent stress-induced cardiac damage by preventing rises in cardiac catecholamines and cyclic-AMP

Phytomedicine, 2011. 8(4):235-244.Med Physiol, 1987. 40:85-87.

• Extracts of rhodiola also significantly inhibit alpha-glucosidase activity ACE.

• Anti-inflammatory effect, decreases seen in CRP levels.

• In animal models of diabetes, rhodiola extract decreases blood glucose and has antioxidant effects demonstrated by reduced lipid peroxidation and increased levels of reduced glutathione.

• Likely secondary to the the tannins and flavonoids such as catechins and proanthocyanidins

• Extract reduces experimentally induced mutations, possibly by increasing the efficiency of intracellular DNA repair mechanisms.

• Rhodiola extracts also demonstrate hepatoprotective and myeloprotectiveeffects.

• In human research found to reduce cortisol.

Rhodiola & AnxietyOpen-label study on effects in the treatment of generalized anxiety disorder (GAD) in 10 patients, men and women, ages 18-64, with a DSM-IV diagnosis of GAD.• Hamilton Depression Rating Scale (HDRS) scores > 17

and Hamilton Anxiety Rating Scale (HARS) 16 or >. • Patients allowed to take SSRIs, SNRIs and

benzodiazepines daily prn. • Rhodax® (Phoenix Laboratories by Bodyonics Ltd.)

340mg daily for 10 weeks.• Assessments included the HARS, HDRS.• Rhodiola group found to have significant decreases in

mean HARS scores at endpoint (p=0.01), as well as a significant difference in HDRS scores (p=0.001).

J AlternComplement Med., 2008. 14(2), 175-80.

Randomized cross-over trial looking at Rhodiola & Mental Performance/Mental Fatigue• 56 young, healthy physicians.• Standardized extract of Rhodiola (SHR-5)

study of fatigue during night duty• Treated with SHR-5 (170mg daily) or

placebo, followed by a 2 week washout and 2weeks with the opposite treatment.

• During the first two weeks of testing, SHR-5 treatment resulted in significant improvement in the mental performance tests.

Nord J Psychiatry, 2007. 61:343-8.

Cognitive Stress in StudentsRCT with placebo arm Rhodaxon on physical and intellectual working capacity and psychoemotional state of foreign students in their first year of studies. • 60 male Indian students studying in Russia. • 660 mg daily for 20 days. • Treatment group showed a 60.7% (p

Rhodiola & Exercise PerformanceRCT/PC to examine the effect of acute and chronic Rhodiola intake on physical capacity, muscle strength, speed of limb movement, reaction time, and attention • 24 healthy young subjects over two sessions• 200 mg rhodiola.• Speed of limb movement, aural and visual reaction time, and

the ability to sustain attention were assessed 1 hr after administration, crossed over to placebo and endurance tests repeated the next day.

• Following a 5-day washout period, the experiment was repeated with the opposite treatment group.

• In the second, longer-term study, 12 subjects were included.• Rhodiola vs placebo, 4 weeks, and then crossed over to

placebo. • Short-term use of Rhodiola significantly increased time to

exhaustion peak compared with placebo. • Longer-term use of Rhodiola lacked effect on any variables.

Int J Sport Nutr.Exerc.Metab2004;14(3):298-307.

Rhodiola on Exercise Induced Inflammation and Muscle Damage

Randomized, double-blind, placebo trial to evaluate the effects of Rhodiola on CRP and CK • 36 healthy volunteers, 21-24 yo.• 340mg of Rhodiola bid 30 days before and 6 days after

exhausting physical exercise (intense mechanical bicylcing)• CRP and CK measured 30 minutes before exercise, 5 hours

after, and five days after. The increase in CRP following exercise was less pronounced in the rhodiola group five hours after exercise (p

RCT/ DB/PCO to evaluate the effects of SHR-5 in the treatment of mild-to-moderate depression • 89 subjects ages of 18 to 70 participated in the 6 week study.

• Participants with initial scores of ≥13 on the Beck Depression

Inventory and ≥21 on the HAMD eligible

• Randomized to one of three groups. Group 1 340mg daily,

Group 2 two 680mg daily, and Group 3 2 placebo tablets daily.

• Statistically significant differences not reported in the average

depression scale scores before the herb extract or placebos

were given.

• Post treatment, both groups given SHR-5 experienced

statistically significant declines in total levels of symptoms

compared to placebo (p

Rhodiola Safety & DosingSafety

• Very low level of toxicity in animal studies.

• The toxic dose for humans is calculated to be about 235,000 mg; the typical daily dose for chronic problems is 360-600 mg per day when standardized for 1% rosavin, 180-300 mg when standardized for 2% rosavin, or 100-170 mg when standardized for 2.6% rosavin.

• May be activating in some individuals, not recommended for patients with BPAD.

Dose

• Clinical trials use products containing 2-3% rosavin and 0.8-1% salidroside. • Dose 100 mg-400 mg/day

Phytomedicine, 2000. 7(5):365-71.Phytomedicine, 2000. 7(2):85-89.

Licorice (Glycyrrhiza glabra)• Traditionally used in TCM for inflammation (heat clearing), digestion (spleen), and vitality

(chi).

• Demonstrates a reliable reduction in testosterone and a highly reliable increase in circulating cortisol after consumption.

• Both of these effects are dose-dependent and not as. Low Glycyrrhizin content (less than 500mg total dose daily) or < 150mg has been confirmed to not influence these hormonal effects.

• Also increases serum DHEA

• Demonstrates high reduction in oxidative stress

• Has the potential to increase blood pressure secondary to increasing cortisol

• Dose: 150-300mg daily, DGL(without glycyrrhizin) up to 1800mg daily for 4 weeks are not associated with toxicity in humans.

https://examine.com/supplements/licorice/#ref169

Ginseng (Panax ginseng)• Improvement in physical stamina, exercise

performance and well-being

• Improvement in mental performance, learning, memory

• Reduction in fatigue• Improved stress response and functioning under

stress

• Glucose regulation/blood sugar reduction in NIDDM

• Improve cardiac function in congestive heart failure

• Improved LDL and HDL levels• Improvement for diminished libido, male fertility

problems, erectile dysfunction

Ginseng• Cancer prevention

• Improved recovery in infection, especially chronic bronchitis, and for the treatment of asthma, COPD, and dyspnea

• Psychological an d physical complaints associated with menopause

• Improvement in metabolism; anabolic effects

• A tonic for the elderly and during convalescence

• Reduction in preeclampsia in pregnant women compared to matched controls

• Neuralgia, convulsions, neurosis, anxiety, insomnia

• Improvement of bifida strains and inhibition of clostridia strains in human intestinal flora

Curcumin - An Adaptogen?• Adaptogenic potential of curcumin seen in an experimental chronic stress

model (mouse study) with prevention (pretx with 25 and 50 mg/kg p.o) of chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis.

• Attenuated chronic stress, biochemical alterations, corticosterone levels, and oxidative stress observed.

• A recent study demonstated that those who took 1000 mg of curcumin for 6 weeks showed lower blood levels of inflammatory cytokines interleukin-1βand TNF-α, as well as lower salivary cortisol.

• A study published in 2016 demonstrated curcumin’s impact specifically in people suffering from occupational stress-related anxiety and fatigue.

J Nat Med. 2011 Jul;65(3-4):532-43Journal of Psychopharmacology 2017. Vol 31, Issue 3, pp. 287 - 302

Curcumin an Adaptogen?• 60 adults with occupational stress disorders were randomly assigned to take an

enhanced-absorption curcumin formula, standard curcumin, or a placebo (all 500 mg twice daily) for 30 days. Compared with the other two groups, those taking the enhanced-absorption curcumin experienced significant improvements in quality of life, stress reduction, anxiety, and fatigue. These improvements correlated with reduced evidence of oxidative damage.

• A study of healthy, middle-aged people, taking an enhanced-absorption curcumin formula produced a wide array of health benefits, including reducing salivary amylase levels (a marker of acute stress), increasing scavenging of free radicals, and lowering blood markers of brain deterioration—all effects that would be expected to reduce the impact of stress in the brain.

• Another study focused on anxiety in obese people at risk for both anxiety and depression. Subjects took curcumin (1,000 mg/day) or a placebo. After 30 days, the curcumin-supplemented subjects experienced a significant reduction in mean anxiety scores.

J Nat Med. 2011 Jul;65(3-4):532-43 •Journal of Psychopharmacology 2017. Vol 31, Issue 3, pp. 287 – 302Nutr J. 2012;11:79. • Chin J Integr Med. 2015;21(5):332-8.

Holy basil: The vitalizerHoly or “sacred” basil calms the mind and spirit, and promotes longevity. This herb, called tulsi in Ayurvedic medicine, is used to improve energy and relieve fatigue, and it elevates the mood, especially providing relief from mild depression. While this herb is related to common basil, that is not a substitute.

It’s suited for when you might say:

• I want a gentle tonic for mind, mood, and immunity.

• I am struggling with depression, anxiety, or low mood.

• I have sleep problems.

• I want help shifting to a new mindset and making healthy lifestyle changes.

• I struggle with mental clarity

• I have chronic inflammation.

• I have high blood sugar, cholesterol, or triglycerides.

• Dose: 2 to 3 mL (40 to 60 drops) tincture in water 3x/day

Maca: The mother of hormone nourishers

The Quechua Indians of Peru consider maca a food that promotes mental acuity, physical vitality, endurance, and stamina. Maca reduces anxiety and depression and is rich in essential amino acids, iodine, iron, and magnesium, as well as sterols that may possess a wide range of activities that support adrenal and hormone function.

It’s suited for when you might say:

• I want more vitality and feel I need deep nourishment.

• I have a low libido.

• I have hormonal imbalances.

• I want to improve my fertility.

• I want to boost my mood, or I have anxiety or depression.

• Dose: 75 to 100 mg/day

Schizandra: The detoxifierSchizandra, revered as an elite tonic herb in traditional Chinese herbalism, is used to improve mental focus, while having calming, anti-anxiety effects. It’s been widely used to enhance athletic performance and endurance, improving energy and stamina in general, and to relieve anxiety.

It’s suited for when you might say:

• I can’t focus. I have brain fog or memory problems.

• I don’t have energy anymore. I tired out easily with physical exertion.

• I have anxiety.

• I want to support or boost my detoxification.

• Dose: 20 to 30 drops of extract 1 or 2x/day or 2 to 4 capsules daily. NOT safe for useduring pregnancy.

Shatavari: The hormonal harmonizer, queen of women’s adaptogens

Shatavari is considered the “Queen of Herbs” in Ayurvedic medicine, where it is beloved as one of the most powerful rejuvenating tonics for women. It is nourishing and calming, as well as hormonally balancing; it is used for irritability and many hormonal imbalances affecting the mood, for example, emotional symptoms of PMS and menopause.

It’s suited for when you might say:

• I feel like I need rejuvenation, balance, and calm.

• I have hormonal imbalances, including PMS, fertility, or menopausal problems.

• Dose: 2-4 mL (40 to 80 drops) of tincture in water 2 to 3x/day

• Cautions: Avoid if you have a history of estrogen-receptor positive cancer

Nervous System Support: Nervines

Hypericum perforatumLavendula officinalisLeonorus cardiacaMatricaria recutitaPassiflora incarnataScutellaria laterifloraValeriana officinalis

St. John’s wortLavenderMotherwortChamomilePassion flowerSkullcapValerian

Nervous System Support: Anxiolytics

Avena sativaEschscholtzia californicaLavendula officinalisLeonorus cardiacaMatricaria recutitaPassiflora incarnataPiper methysticumScutellaria laterifloraValeriana officinalis

Milky oatsCalifornia poppyLavenderMotherwortChamomilePassion flowerKava kavaSkulllcapValerian

HPA Axis “Nutritional” Support • Vitamin C – replace losses

• B-complex – precursor to catecholamines, glucorticoids, DHEA

• PS (400 mg/day)– improved stamina, cognitive function, possible blunting of HPA response to acute stressors

• Also consider 5-HTP, GABA, L-theanine (TBD in Mind and Mood)

• DHEA (10-100mg/day)- improved aging parameters; buffers stress response, possible benefits for menopausal women w/sex. dysfunctiona and HPA-Axis-D. Can be used po, subling, micronized (converts to DHEA-S most readily).Poss androgens in some women.

• Pregnenalone- little data for HPA-Axis-D; steroid hormone precursor

nmwi

HPA Axis Summary• Obtain history and timeline

• Apply history to matrix

• Assess for symptoms of SRS-D/SOS

• Rule out other causes

• Test for allostatic load

• Assess for Root Causes of SOS: circadian rhythm disruption, inflammation, stress, blood sugar imbalances and restore

• Assess for Specific Systemic Imbalance: leaky gut à inflammation, hypothyroidism, etc.

• Address Root Causes with Add/Remove model in diet, lifestyle, etc.

• Remember the HEART model and Total Women’s Ecology

nmwi