Adaptogens are plant derived compounds that normalize endocrine function and promote adaptation to environmental stress. Adaptogenic herbs modulate stress responses, enhancing energy production and sleep quality and improving immune function. Eleuthero Root (Eleutherococcus), Holy Basil (Ocimum), and Rhodiola (Rhodiola) have been used for the treatment of stress, fatigue, sleep disturbances, elevated cortisol levels, adrenal deficiency, low DHEAS and alterations in DHEAS/cortisol ratio, chronic infection, impaired memory, and exercise intolerance. Adaptogens have been used as single agents or in combination with other plant-derived products such as Panax quinquefolius, Withania somnifera, Glycyrrhiza spp,Schisandra chinensis, and Gynostemma pentaphyllum. Other herbs that have shown efficacy as adjuncts to adaptogens include Scutellaria lateriflora,Matricaria recutita, Tilia spp, Hypericum perforatum and Melissa officinalis, which are known for their calming effect on the nervous system. Eleuthero root and rhodiola have been associated with anxiety and insomnia, although these effects have not been validated in clinical studies. Adverse effects of Eleutherococcus such as increased blood pressure in hypertensive patients and heart palpitations have occurred as a result of inappropriate dosing. Overall, adaptogenic herbs are safe and no known drug interactions exist with the exception of a few cases of accidental misidentification of the herb, and their broad range of beneficial effects supports their development as valuable agents for the treatment of a variety of conditions.
AARM REFERENCE REVIEWS:
These are AARM reference reviews in which clinicians can obtain a quick overview of understanding with respect to how herbs, nutrients, and hormones can be used effectively in clinical practice. The dosages recommended are based on therapeutic results. Side effects that have not been seen in clinical experience or found in clinical studies but only been theorized have been identified and depicted as Unsubstantiated Theoretical Concerns.
Since many nutrients and herbs on the market have not gone through double-blind studies but have been used extensively in clinical settings for hundreds, and for some thousands of years, these reference reviews have attempted to give a unified opinion on how to use these herbs effectively. The opinions expressed are from different professors and experts in the field of nutritional and botanical medicine. Some information is based on personal opinions and can not be quantified as fact. However, if clinicians only restricted themselves to what is fully proven by double-blind studies, the art of healing and restoring health with nutrients and herbs would be lost.
Adaptogens are a category of herbs that may increase an organism’s ability to adapt to its environment1. It is possible that adaptogenic herbs can prevent, treat, and enable people to recover from the effects of acute or long-term stress.
KEY HERBS DISCUSSED:
Eleuthero Root (Eleutherococcus), Holy Basil (Ocimum), and Rhodiola (Rhodiola)
Stress, fatigue, poor sleep, elevated cortisol, adrenal deficiency, low DHEAS, altered DHEAS/cortisol ratio, chronic infections, impaired memory and mental function, exercise intolerance, easy exhaustion with moderate exertion.
ADJUNCTIVE OR STAND-ALONE TREATMENT:
The herbs discussed in this review may be used either as an adjunctive or a stand-alone treatment for the above indications.
DOSE OF BIOACTIVE CONSTITUENTS:
Eleuthero Root (Eleutherococcus) (whole plant extracts) 80-900 mg per day; containing a minimum of 4 mg eleutherosides daily
Holy Basil (Ocimum) (whole plant extracts)80-900 mg per day
Rhodeola (Rhodeola)300 mg BID, containing a minimum of 1 mg Salidrocide Glycosides
SYNERGISTIC HERBAL FORMULA:
Eleuthero root (Eleutherococcus), Sarsparilla (Smilax), Rhodeola (Rhodiola), Holy Basil (Tulsi), other herbs to consider are Panax quinquefolius, Withania somnifera, Glycyrrhiza spp, Schisandra chinensis, Gynostemma pentaphyllum. Nervine (calming) herbs such as Scutellaria lateriflora, Matricaria recutita, Tilia spp, Hypericum perforatum, and Melissa officinalis are also useful adjuncts to adaptogens.
SIDE EFFECTS (AND CAUTIONS):
The key herbs discussed can be safely used when used appropriately. A few cases of drug interaction have been mistakenly blamed with Eleuthero Root as the herb was accidentally misidentified as the toxic herb Periploca.
UNSUBSTANTIATED THEORETICAL CONCERNS:
Although some Eleutherococcus users report symptoms of stimulation, anxiety and insomnia, it has not been validated in clinical studies. There has been some concern that Eleutherococcus may increase blood pressure in hypertensive patients, or promote heart palpitations–side effects suggested to occur with excessive and inappropriate dosing. Clinical studies have not substantiated any of these theoretical concerns. Rhodiola may also be stimulating and theoretically promote anxiety, heart palpitations, and insomnia.
Adaptogens are herbs capable of restoring normal tone and function to the HPA (Hypothalamic/ pituitary/adrenal) axis and SAS (sympatho-adrenal system), and therefore to the entire body. Adaptogens are considered safe agents that normalize endocrine function through numerous broad and non-specific actions, and increase overall resistance to stressors. Because of this rather vague description, the term “adaptogen” has not been widely adopted in mainstream Western medicine. Nevertheless, adaptogenic herbs possess some unique actions on the adrenal system that tend to promote resistance to the negative effects of stress on the body.
The adrenal glands underlie much of the body’s response to external and internal stressors. Likewise, stress is a primary contributor to adrenal/HPA axis dysfunction. Adaptogenic herbs may improve resistance to stress as well as prevent some of the more common symptoms of stress (e.g., poor concentration, sleep disturbance, fatigue, decreased immune response, and decreased resistance to infections). Adaptogenic herbs modulate stress responses, prevent down-regulation of the adrenal glands, enhance energy production and sleep quality, and improve immune function. This review will elucidate current research on the use adaptogenic herbs for the adrenal axis, and general human health and well-being.
THE HPA AXIS AND ADRENAL GLAND HEALTH
The HPA axis encompasses the synergism and feedback between adrenal hormones, and hormones released by the hypothalamus and pituitary gland. The hypothalamus and pituitary gland are greatly affected by stress, and the emotional state of the individual person. The effect of the HPA axis on the emotional state was first described in the field of psychology, where biochemical adaptations noted from long-term stress and overwork led to sleep disturbances, irritability, and exhaustion. One portion of the HPA axis activated by stress is known as SAS. Psychological and physical challenges cause acute stress responses involving brain neurotransmitters that in turn affect the release of corticotropins and other hormones from the pituitary gland and hypothalamus. The pituitary and hypothalamic hormones subsequently act on the adrenal glands. Long-term stimulation of the adrenal glands leads to adrenal gland dysfunction.; the glands become hypertrophic, less responsive, or erratically responsive as evidenced by abnormal cortisol release, ACTH response, and altered DHEA to cortisol ratios (as well as other hormonal regulation disturbances). Chronic stress and the resultant increase in cortisol are known to suppress normal white blood cell activity, which subsequently is associated with altered cytokines and a greater incidence of inflammatory and allergic responses. Impairment and disturbance in the HPA axis is also associated with reproductive and metabolic dysfunctions, as well as altered psychological presentations (e.g., anxiety and depression).
THE HPA AXIS AND ADAPTOGENIC HERBS
Hsp70 is a molecular chaperone sometimes referred to as a stress sensor; it helps the body to repair damaged proteins that arise from chronic stress and inflammation. Hsp70 inhibits the expression of NO (nitric oxide) synthase II genes and interacts with glucocorticoid receptors directly and via kinase enzymes, thus affecting the levels of circulating cortisol and NO. Prevention of the stress-induced increase in NO (and the associated decrease in ATP production) results in increased performance and endurance; Eleutherococcus, Schisandra, and Rhodiola help the body elaborate specific heat shock proteins (Hsp). In addition, adaptogen herbs have also demonstrated significant antioxidant effects in humans. Reducing oxidative stress in the body with adaptogen herbs may improve overall health and well-being.
Eleutherococcus (Siberian ginseng) is a member of the Araliaceae family and a commonly used adaptogen. Not only is this herb commonly used in Russia (where the first studies were conducted in the 1950s), but in North America and throughout the world. Native to Siberia and the northern regions of Russia, the Korean peninsula, and the northeast region of China, Eleutherococcus has Panax ginseng-like effects. Interestingly, in Greek, the wordEleutheros means ‘free’, and the word kokkos means ‘seed’. Meanwhile, Eleutherococcus is known as Acanthopanax senticosus in China, and some research studies and texts still use this older nomenclature for this herb.
Beginning in the 1950s, the scientific literature on Eleutherococcus reported that it improved stress tolerance and energy, increased resistance to infection, and acted as an adrenal tonic. Eleutherococcus has demonstrated stress-relieving effects on the HPA axis, reducing excessive corticotropin release and optimizing adrenal response. Eleutherococcus may act directly on the hypothalamus to regulate hormones, including mineralocorticoids, glucocorticoids, and reproductive hormones. Syringen, lignans, and sesamin found in this plant have been shown to exert immune-enhancing effects.
Eleutherococcus contains coumarins, steroidal glycosides, and a group of polysaccharides, eleutherosides A, B, C, D, and E, which have significant immune-stimulating properties. Among the specific conditions where Eleutherococcus has shown possible effects are in treating immune depression (i.e., compromise), head colds, influenza, bronchitis, respiratory allergies, atherosclerosis, rheumatic valve lesions, arrhythmias, arthritis, chemotherapy side effects, and altitude sickness, as well as for general weakness, fatigue, stress intolerance, and nervous debilities. Some of the anti-allergy and anti-inflammatory responses may relate to inhibition of nitric oxide synthase and cyclooxygenase during macrophage activation.
Numerous studies have demonstrated the ability of Eleutherococcus to enhance physical stamina in athletes and also inhabitants of high altitudes. The herb may increase oxygen consumption and utilization and increases overall work performance, though this effect is not seen in all studies. The mechanisms identified include improved physical stamina via adrenal responses as well as improved glucose uptake/metabolism in muscle cells and prevention of nitrogen depletion. Positive effects on fibrinogen and blood coagulation have been demonstrated and proposed as another mechanism of enhanced exercise performance. Eleutherococcus has been shown to improve general mental function, well-being and quality of life in the elderly.Eleutherococcus is reported to affect noradrenalin responses in the brain in a manner that helps to blunt the stress response. Specifically, the paraventricular and supra optic nuclei (regions of the brain found to be integral to stress responses) are affected.
Ocimum sanctum (Holy Basil or tulsi) is a plant species from India. Ocimum is in the Lamiaceae (mint) family and has been used traditionally in the treatment of diabetes, stress, ulcers and inflammation. Agrawal and colleagues showed its ability to reduce fasting and postprandial blood glucose levels in humans. Ocimum sanctum also has anti-inflammatory properties. Ocimum has been found to promote glutathione transferase, reductase, and peroxidase enzymes as well as promote superoxide dismutase Ocimum contains common anti-inflammatory flavonoids such as apigenin, luteolin, and one unique to Ocimum (called ocimarin). Other constituents include ocimumosides and cerebrosides. Oil extracted from the seeds can reduce inflammation by lipoxygenase inhibition and histamine antagonism and can help to heal ulcers. In addition to its antioxidant properties, modern research has shown Ocimum to be radioprotective, anticarcinogenic and cardioprotective. The ocimumosides in Ocimum have anti-stress effects in that they help to normalize hyperglycemia, corticosterones, and adrenal hypertrophy from chronic stress. Ocimum has been shown to reduce serum cortisol and glucose.
Numerous effects on the brain, neurotransmission, and stress response have been demonstrated by Ocimum. Ethanol extracts of Ocimum tend to blunt the stress response in animals regardless of the experimental protocol. The plant extract reduced behavioral and neurochemical responses to stress in the swimming endurance test and gravitation, restraint stress, and noise stress. In fact, noise pollution has been shown to be a real and significant stress causing changes in the central nervous system’s neurotransmitter balance and activity. Exposure to constant, irritating noise can lead to increased dopamine and serotonin in the brain, with a simultaneous reduction in acetylcholine and an increase in acetylcholinesterase, presumably as a stress response to the noise irritation. Response to a noise stimulus may be used as a research tool to evaluate the effects of stress-alleviating herbs and medications. Ocimum has been shown to prevent the above changes in brain neurotransmitters suggesting an anti-stress effect directly within the central nervous system. Animal studies have demonstrated a dopaminergic activity that promoted a calming and mood stabilizing activity. One study found enhancement of GABA neurotransmission enabled Ocimum to exert a normalizing effect on immune modulation.
Like other adaptogens, Ocimum has been shown to prevent both humoral and cell-mediated responses associated with stress, and researchers point to calming mechanisms as underlying contributors. These calming effects may also extend to the vasculature as Ocimum has been shown to be both vasodilating and hypotensive. It has demonstrated positive effects on cognitive ability and has possible application for dementia while animal studies have shown anticonvulsant affects. All of the above demonstrate the plant’s adaptogen normalizing effects on the brain and neurotransmission.
Rhodiola rosea (Rose Root or Golden Root) is a member of the Crassulaceae family. It is a widely used adaptogen and anti-stress herb for mood disorders, fatigue, and adrenal weakness. This plant is native to Russia, where most of the initial scientific and clinical research was conducted.Rhodiola contains rosavin, rosarin, rosin, tyrosol and salidroside, and these are often used as markers to standardize Rhodiola extracts. The herb’s main use is as an adaptogen for mood disorders, sleep difficulties, irritability, fatigue, poor concentration, headaches, vascular stress, and generalized deficiency states. Rhodiola elevates serotonin levels in the central nervous system in animal models of depression and hippocampal suppression.Rhodiola is believed to exert antidepressant, anti-anxiety and adaptogenic effects.
Cardiac complaints that arise from stress (such as hypertension and arrhythmias) may respond to Rhodiola therapy. As with other adaptogenic herbs, its cardio-protection may minimize ischemic injury. Antiarrhythmic effects are due to its ability to block excessive epinephrine-driven stimulation and activation of opiate pathways in the central nervous system.
In a rat model of acute stress, Rhodiola prevented changes in behavior, immunity and hormonal regulation to the same degree as fluoxetine. Certain stress-inducing paradigms can cause reproducible effects on serotonin, cell proliferation, and differentiation in the central nervous system. Rhodiolaincreased serotonin and had a normalizing effect on hippocampal stem cells and related structures of the brain in studies, restoring them to levels seen in non-stressed control animals. One research study in humans found Rhodiola supplementation improved energy and promoted mental focus and concentration in chronic fatigue syndrome (CFS) patients while normalizing their cortisol levels.
ADAPTOGEN HERBS FOR GENERAL HEALTH
DISCLOSURE OF INTERESTS
Dr. Saunders reports personal fees related to employment or seeing patients from CCNM, the Dundas Naturopathic Centre, and from Beaumont Health Systems, Troy Hospital, MI, outside the submitted work. Dr. Winston reports personal fees from Herbalist & Alchemist, Inc, outside the submitted work. Dr. Stansbury has nothing to disclose.
- Panossian A, Wikman G, Kaur P, Asea A. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones.
- Bleakney TL. Deconstructing an adaptogen: Eleutherococcus senticosus.
- Cicero AF, Derosa G, Brillante R, Bernardi R, Nascetti S, Gaddi A. Effects of Siberian ginseng (Eleutherococcus senticosus maxim.) on elderly quality of life: a randomized clinical trial.
- Ambroziak U, Bednarczuk T, Ginalska-Malinowska M et al. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency – management in adults.
- Breslow MJ, Ligier B. Hyperadrenergic states.
- Sebaai N, Lesage J, Vieau D, Alaoui A, Dupouy JP, Deloof S. Altered control of the hypothalamo-pituitary-adrenal axis in adult male rats exposed perinatally to food deprivation and/or dehydration.
- Golotin VG, Gonenko VA, Zimina VV, Naumov VV, Shevtsova SP. [Effect of ionol and eleutherococcus on changes of the hypophyseo-adrenal system in rats under extreme conditions].
- Wiegant FA, Surinova S, Ytsma E, Langelaar-Makkinje M, Wikman G, Post JA. Plant adaptogens increase lifespan and stress resistance in C. elegans.
- Chen TS, Liou SY, Chang YL. Antioxidant evaluation of three adaptogen extracts.
- Davydov M, Krikorian AD. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look.
- Gaffney BT, Hugel HM, Rich PA. The effects of Eleutherococcus senticosus and Panax ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes.
- Gaffney BT, Hugel HM, Rich PA. Panax ginseng and Eleutherococcus senticosus may exaggerate an already existing biphasic response to stress via inhibition of enzymes which limit the binding of stress hormones to their receptors.
- Deyama T, Nishibe S, Nakazawa Y. Constituents and pharmacological effects of Eucommia and Siberian ginseng.
- Brekhman II, Dardymov IV. New substances of plant origin which increase nonspecific resistance.
- Aicher B, Gund H, Schultz A. Eleutherococcus senticosus: Therapie bei akuten grippalen infekten.
- Facchinetti F, Neri I, Tarabusi M. Eleutherococcus senticosus reduces cardiovascular stress response in healthy subjects: a randomized, placebo-controlled trial.
- Maslov LN, Lishmanov YB, Arbuzov AG et al. Antiarrhythmic activity of phytoadaptogens in short-term ischemia-reperfusion of the heart and postinfarction cardiosclerosis.
- Park SH, Kim SK, Shin IH, Kim HG, Choe JY. Effects of AIF on Knee Osteoarthritis Patients: Double-blind, Randomized Placebo-controlled Study.
- Jung CH, Jung H, Shin YC et al. Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophage.
- Asano K, Takahashi T, Miyashita M et al. Effect of Eleutherococcus senticosus extract on human physical working capacity.
- Dowling EA, Redondo DR, Branch JD, Jones S, McNabb G, Williams MH. Effect of Eleutherococcus senticosus on submaximal and maximal exercise performance.
- Eschbach LF, Webster MJ, Boyd JC, McArthur PD, Evetovich TK. The effect of siberian ginseng (Eleutherococcus senticosus) on substrate utilization and performance.
- Niu HS, Liu IM, Cheng JT, Lin CL, Hsu FL. Hypoglycemic effect of syringin from Eleutherococcus senticosus in streptozotocin-induced diabetic rats.
- Azizov AP. [Effects of eleutherococcus, elton, leuzea, and leveton on the blood coagulation system during training in athletes].
- Soya H, Deocaris CC, Yamaguchi K et al. Extract from Acanthopanax senticosus harms (Siberian ginseng) activates NTS and SON/PVN in the rat brain.
- Agrawal P, Rai V, Singh RB. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus.
- Devi PU, Ganasoundari A. Modulation of glutathione and antioxidant enzymes by Ocimum sanctum and its role in protection against radiation injury.
- Sood S, Narang D, Thomas MK, Gupta YK, Maulik SK. Effect of Ocimum sanctum Linn. on cardiac changes in rats subjected to chronic restraint stress.
- Singh S, Taneja M, Majumdar DK. Biological activities of Ocimum sanctum L. fixed oil–an overview.
- Singh S, Majumdar DK. Evaluation of the gastric antiulcer activity of fixed oil of Ocimum sanctum (Holy Basil).
- Sood S, Narang D, Dinda AK, Maulik SK. Chronic oral administration of Ocimum sanctum Linn. augments cardiac endogenous antioxidants and prevents isoproterenol-induced myocardial necrosis in rats.
- Gupta P, Yadav DK, Siripurapu KB, Palit G, Maurya R. Constituents of Ocimum sanctum with antistress activity.
- Gholap S, Kar A. Hypoglycaemic effects of some plant extracts are possibly mediated through inhibition in corticosteroid concentration.
- Maity TK, Mandal SC, Saha BP, Pal M. Effect of Ocimum sanctum roots extract on swimming performance in mice.
- Sen P, Maiti PC, Puri S, Ray A, Audulov NA, Valdman AV. Mechanism of anti-stress activity of Ocimum sanctum Linn, eugenol and Tinospora malabarica in experimental animals.
- Sembulingam K, Sembulingam P, Namasivayam A. Effect of Ocimum sanctum Linn on noise induced changes in plasma corticosterone level.
- Sembulingam K, Sembulingam P, Namasivayam A. Effect of Ocimum sanctum Linn on the changes in central cholinergic system induced by acute noise stress.
- Ravindran R, Rathinasamy SD, Samson J, Senthilvelan M. Noise-stress-induced brain neurotransmitter changes and the effect of Ocimum sanctum (Linn) treatment in albino rats.
- Samson J, Sheela DR, Ravindran R, Senthilvelan M. Biogenic amine changes in brain regions and attenuating action of Ocimum sanctumin noise exposure.
- Sakina MR, Dandiya PC, Hamdard ME, Hameed A. Preliminary psychopharmacological evaluation of Ocimum sanctum leaf extract.
- Mediratta PK, Sharma KK, Singh S. Evaluation of immunomodulatory potential of Ocimum sanctum seed oil and its possible mechanism of action.
- Singh S, Rehan HM, Majumdar DK. Effect of Ocimum sanctum fixed oil on blood pressure, blood clotting time and pentobarbitone-induced sleeping time.
- Joshi H, Parle M. Evaluation of nootropic potential of Ocimum sanctum Linn. in mice.
- Jaggi RK, Madaan R, Singh B. Anticonvulsant potential of holy basil, Ocimum sanctum Linn., and its cultures.
- Kelly GS. Rhodiola rosea: a possible plant adaptogen.
- Chen QG, Zeng YS, Qu ZQ et al. The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats.
- Perfumi M, Mattioli L. Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L extract in mice.
- Kucinskaite A, Briedis V, Savickas A. [Experimental analysis of therapeutic properties of Rhodiola rosea L. and its possible application in medicine].
- Arbuzov AG, Maslov LN, Burkova VN, Krylatov AV, Konkovskaia I, Safronov SM. [Phytoadaptogens-induced phenomenon similar to ischemic preconditioning].
- Maimeskulova LA, Maslov LN, Lishmanov I, Krasnov EA. [The participation of the mu-, delta- and kappa-opioid receptors in the realization of the anti-arrhythmia effect of Rhodiola rosea].
- Mattioli L, Funari C, Perfumi M. [Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats].
- Qin YJ, Zeng YS, Zhou CC, Li Y, Zhong ZQ. [Effects of Rhodiola rosea on level of 5-hydroxytryptamine, cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress].
- Olsson EM, von SB, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of th