Herbal Treatments For Adrenocortical Dysfunction

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To compensate for increased stressors, many individuals have turned to ergogenic or energy enhancement substances. These herbal and nutritional supplements are thought to have some type of ergogenic activity and are among the best-selling natural products in nutrition stores, with a financial impact in the $2-$3 billion per year range. Although there is a body of scientific literature on a variety of natural ergogenic substances—such as pyruvate, creatine, ephedra (ma huang; Ephedra sinica), ginseng (Panax spp.), and guarana (Paullinia cupana)— using animal models, there are few well-designed human clinical trials. This lack of legitimate research and the high over-the-counter use of natural products suggest an urgent need to conduct studies on the long-term effectiveness and safety of these natural ergogenic aids. Natural products (such as phytopharmacologic agents), which appear to enhance performance capacity (as demonstrated in animal and human studies), include such nutrients as creatine and pyruvate and such herbs as guarana, ginseng, Siberian ginseng (eleuthero; Eleutherococcus senticosus), schisandra (Schisandra chinensis), and ashwagandha (Withania somnifera).79-81 Other botanicals with purported ergogenic efficacy include regular coffee (Coffea arabica), cola nut (Cola accuminata), and ephedra. These herbs are thought to have ergogenic effects because they contain methylxanthine compounds (cola nut and coffee beans), which have been shown to mimic the effects of endogenous epinephrine (ephedra). Caffeine, a methylxanthine, has been shown, in human trials, to enhance endurance and exercise performance.82 Perhaps the most misunderstood of all adrenal tonic herbs are the adaptogens. The term adaptogen, coined by Dr. Israel Brekhman, was proposed as a more appropriate description for isolated phytochemical compounds. Adaptogens, first identified in 1966 by Brekhman, are, collectively, a group of medically effective substances that put organisms into nonspecific heightened resistance states to help organisms to combat stressors and adapt to extraordinary

Table 1-1. Botanicals for Treating Adrenocortical Dysfunction

Botanical Agent

Mechanism of Action

Licorice (Glycyrrhiza glabra)

Hog weed (Boerhaavia diffusa)

Ashwagandha (Withania somnifera)

Siberian ginseng (Eleutherococcus senticosus)

Unknown

10-60 drops 3-4 times per day of fresh plant-liquid extract or 1-6 g daily of the whole herb in capsule or teaa Dry strength liquid extract: 20-60 drops 1-4 times per day

Suppresses 5b-reductase activity; inhibits 11b-hydroxysteroid-dehydrogenase, which converts active cortisol into inactive cortisone; may cause blood pressure elevations requiring monitoring Buffers plasma cortisol elevation; reverses adrenal cortisol depletion under high levels of stress Glucocorticoid-like effects from plant sterols

Binds to mineral and extract: 20-60 glucocorticoid-receptors aTilgner S. Herbal Medicine: From the Heart of the Earth. Cottage Grove, OR: Wise Acres Press, 1999.

challenges. These herbs are of most interest to nutritionally minded physicians as substances that can enhance an individual's resistance to the long-term, cumulative effects of highvolume and high-intensity stress (such as exercise). Perhaps the most studied of the adapto-genic herbs are Siberian ginseng (Eleuthero) and licorice (Glycyrrhiza glabra). The purported mechanism of action of licorice is to reduce the amount of hydrocortisone broken down via inhibition of 11-beta-hydroxysteroid-dehydrogenase, which converts active cortisol into inactive cortisone. Eleuthero may act as an adaptogen by regulation of glucose metabolism and enhancement of immune function. These herbs were the first to be studied as adaptogens. Additional first-generation adaptogens include schisandra and reishi (Ganoderma lucidum).83 There are additional botanical agents that have been reported to have adaptogenic qualities, but these agents have not been studied extensively for their support of the adrenal system. These include: ashwaganda, gotu kola (Centella asiatica), wild oats (Avena sativa), astragalus (huang chi; Astragalus membranaceous), fo-ti or hoshouwu (Polygonum multiflorum), burdock (Arctium lappa), Siberian Ginseng (Eleutherococcus senticosus) and suma (Pfaffia paniculata).

Withania somnifera (Ashwagandha)

Withania somnifera is a medicinal plant used in Ayurvedic medicine. Historically, this adaptogenic herb has been used to modulate the stress response as well as for immune modulation, and anti-inflammatory, anti-tumor, and antioxidant activity.84 Research using animal models indicates that supplementation with ashwagandha moderates the stress response when exposed to chronic environmental stressors, including attenuation of symptoms such as depression, increased blood sugar, glucose intolerance, increased cortisol, cognitive deficits and stomach ulcers.85 Additional studies have shown that ashwagandha exhibits anti-anxiety and antidepressant activity comparable to pharmaceutical agents.86 Research has also demonstrated that ashwagandha exhibits neuroprotective activity in the hippocampus with induced environmental stress. This study showed an 80% decrease in the number of degenerating cells in the hippocampus with ashwagandha compared to controls.87 Studies using animal models have also demonstrated ashwagandha supplementation increases antioxidant enzymes as well as decreases stress-induced gastric ulcers.88 Research has revealed immune modulating effects by up-regulation of Th-1 immune response measured by significant increases in CD4 and CD8 levels with ashwagandha root supplementation.89 Ashwagandha root also has been shown to decrease total plasma lipids, cholesterol, triglycerides, and lipid peroxidation and increase HDL levels in hypercholesterolemic animals.90

Eleutherococcus senticosus (Eleuthero; Siberian Ginseng)

Siberian ginseng is another adaptogenic herb used for various immune and stress modulating effects. Studies with animal models indicate that Siberian ginseng supplementation combined with induced physical stress showed inhibition of elevation in serum cortisol, inhibition of the reduction in natural killer cell activity, and increased physical endurance.91 Studies indicate that the constituents in Siberian ginseng also exhibit immune stimulating, antibacterial, cholesterol lowering, antioxidant, anti-cancer, and insulin modulating activity.92

Panax Ginseng (Korean Ginseng)

Panax ginseng has been traditionally used in Asian countries as an adaptogenic herb to modulate stress, fatigue, and immune function. Ginseng has numerous active constituents, most notably are the triterpenoid saponins referred to collectively as ginsenosides. Research shows that ginseng saponins directly influence the HPA axis. Animal models show that these saponins increase plasma levels of ACTH and cortisol, and this stimulation is suppressed by dexa-methasone suggesting they act via the hypothalamus.93 Panax has also been shown to increase DHEA sulfate and improve the cortisol : DHEA ratios in menopausal women. Panax also stimulates the Th-1 immune response. Studies show an increase in IgA production, and the Th-1 cytokines interleukin-2 and interferon-gamma as well as interleukin-10. Also, the activity of natural killer cells was increased.94 Evidence suggests that Panax ginseng exhibits antioxidant, anti-cancer, and anti-inflammatory activity. Research shows that Panax provides protection of neurons from toxicity and hypoxia, improve cognitive performance, exhibits anti-atherosclerotic and antihypertensive activity, improves wound healing, decreases allergic response, and enhances insulin sensitivity.95

Rhodiola rosea

Rhodiola is another medicinal plant used to tonify and for general balancing. A double-blind crossover study performed with humans showed that Rhodiola supplementation improved mental fatigue and cognition under stressful conditions.96 Investigation of Rhodiola also demonstrates that this herb prevents stress-induced cardiac damage by preventing catacholamine release and higher cAMP levels in the myocardium associated with increased stress.97 Rhodiola has numerous other traditional uses as well. It exhibits antidepressant and anti-cancer activity, improves physical and mental performance, and increases endogenous opioid peptides.98

Botanicals with Purported Adaptogenic Properties

American ginseng (Panax quinquefolium)

Ashwagandha (Withania somnifera)

Astragalus (Astragalus membranaceus) root

Borage (Borago officinalis)

Bupleurum (Bupleurum chinense)

Cola nut (Cola nitida)

Devil's club (Oplopanax horridum)

Echinacea (Echinacea spp.)

Ginseng (Panax spp.)

Korean ginseng (Panax Ginseng)

Licorice (Glycyrrhiza glabra)

Matricaria chamomile

Oats (Avena sativa)

Prickly ash (Xanthoxylum clava-herculis) bark Siberian ginseng (Eleutherococcus senticosus) Scullcap (Scutellaria lateriflora) Suma (Pfaffia paniculata) Turmeric (Curcuma longa)

From: Tilgner S. Herbal Medicine: From the Heart of the Earth. OR: Wise Acres Press, 1999.

Camellia sinensis

Camellia sinensis, commonly known as green tea, is well known for its antioxidant, antiinflammatory, and anti-cancer properties. Additionally, it is believed to improve cardiovascular health, protect the skin from ionizing radiation, and enhance weight loss.99 The amino acid theanine is one of the constituents of green tea. Human studies show that oral intake of theanine attenuates the sympathetic response to an acute stressor. Specifically, a decrease in heart rate and salivary immunoglobulin A was demonstrated.100 Theanine increases dopamine and serotonin levels in the brain, which may accountfor itsanxiolyticactivity.101 Also, animal models also show that theanine decreases blood pressure in spontaneously hypertensive rats.102

Matricaria chamomile

Matricaria chamomile, also known as Chamomilla recutita, has been shown to modulate the HPA axis. Animal models have shown that chamomile supplementation reduced cortisol levels in response to an acute stressor.103 Additionally, chamomile inhalation decreased the stress-induced increase in ACTH levels.104 The constituent in chamomile apigenin has been shown to bind the central benzodiazepine receptors inducing anxiolytic and slight sedating effects.105

Holy Basil

Research has documented that holy basil (Ocimim sanctum) acts as an antioxidant and may decrease levels of stress hormones.106 This herb is a powerful anti-inflammatory that has an effec tiveness that is similar to aspirin and ibuprofen. However, unlike aspirin and ibuprofen, this herb is not irritating to the lining of the stomach. Animal studies have found that holy basil has similar effects to a variety of mood-enhancing pharmaceuticals, such as stimulants and antidepressants.

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