Rehmannia
Rehmannia glutinosa, root dry
American ginseng
Panax quinquefolius, root dry
Wild oats
Avena sativa, herb dry
Lavender
Lavendula angustifolia, herb dry

• Improves physical and mental performance under stress
• Anxiolytic and nervine

• Fatigue
• Nervous exhaustion/Mental Fatigue
• Anxiety

A combination of Rehmannia, American ginseng, lavender and wild oats can aid the body’s ability to adapt to stress. These herbal extracts help sustain a healthy response to stress by regulating both central nervous system (CNS) and hypothalamic-pituitary-adrenal (HPA) axis function (Figure 1).^[1] Rehmannia and American ginseng have a long history of traditional use for nervous exhaustion. Additionally, lavender has a long history of use as an anxiolytic to help address restlessness, agitation, and insomnia associated with ongoing stress. Traditionally, wild oats are used as nervous system tonic, helping to induce feelings of calmness. Providing non-stimulating, nourishing, and restorative benefits, this combination may help to re-establish healthy HPA axis function during times of stress.

Prolonged stress is associated with numerous symptoms, including fatigue, exhaustion, tiredness, and weakness.^[3] Fatigue symptoms can drive stress levels, impacting cognitive abilities and concentration, and reducing one’s overall ability to adapt to environmental stressors.

The body’s response to stress is governed by the HPA axis. In response to environmental stress, the hypothalamus releases corticotrophin-releasing hormone (CRH), stimulating the pituitary gland to release adrenocorticotropic hormone (ACTH). This in turn signals the adrenal gland to produce glucocorticoids (cortisol), that bind to glucocorticoid receptors in the brain. In response to elevated glucocorticoids, the body decreases CRH release, forming a feedback axis between the hypothalamus and the adrenal glands, which effectively dials down HPA activation.^[4]

However, in the context of prolonged stress, chronically elevated cortisol activity can lead to exhaustion. Left unmanaged, chronic stress can lead to an unregulated allostatic response characterised inability to adapt to stress and balance HPA activity.^[4] As a result of HPA overactivation, the body downregulates cortisol output to curb excess glucocorticoid exposure in the body.^[5] Consequent to this, HPA response falls into a state of dysfunction, limiting its ability to adapt to stress appropriately. To resolve symptoms that arise from chronic HPA over activation, supporting the restoration of the HPA axis can assit individuals experiencing stress-induced exhaustion.

Adaptogens directly support HPA activity to aid stress adaptation and increase resilience. Rehmannia and American ginseng are adaptogenic herbs that have demonstrated the ability to increase mental capacity in times of stress and fatigue. Together, these herbal extracts may enhance tolerance to mental exhaustion with neuroprotective, anti-fatigue and anxiolytic effects.^[6] American ginseng is highly regarded for its ability to enhance physical performance, vitality and resilience via effects that can support HPA axis function via reduction of oxidative stress and the attenuation of cortisol production.^[7-9] These effects are attributed to the action of a group of ginseng-specific saponins known as ginsenosides associated with HPA axis enhancing benefits.^[8,9] Therefore, the use of adaptogens could increase the body’s ability to cope with stress, and minimize sensitivity to stress, supporting a greater ability to cope with and adapt to stress.

The anxiolytic effects of American ginseng are linked to the interaction between ginsenosides and gamma-aminobutyric acid (GABAA) receptors, as shown in animal studies.^[10] Supporting this, in vitro studies demonstrate that ginsenosides modulate nerve transmission by decreasing the availability of neurotransmitters like GABAA, glutamate, dopamine, noradrenaline, and serotonin in the brain.^[10]

Evidence shows that ginsenoside Rg3, the most active ginsenoside, interacts with and regulates voltage and ligand-gated ion channels. It does this by interacting with specific amino acids at the channel entryways or pore regions, which are associated with ion influx or efflux. This activity modulates nerve function and supports brain channel regulation.^[10]

Overall, this evidence highlights the potential of American ginseng as a preventative and supportive therapy for various nervous system disorders.^[11]

Wild oats extracts and tinctures have a long history of medicinal use for various psychotropic purposes, including alleviating anxiety and inducing calmness. Oats contain phytochemicals that have been shown to affect brain function and cognitive performance in humans.^[12] Notably, wild green oats extracts can inhibit the enzymes monoamine oxidase-B (MAO-B) and phosphodiesterase 4 (PDE 4). ^[12] This inhibition suggests potential benefits for cognitive function and mood by preventing the breakdown of monoamine neurotransmitters and cyclic adenosine monophosphate (cAMP).^[12]

Lavender has a long history of use as an anxiolytic, sedative, and calming agent.^[13] Research has shown that lavender oil can help with anxiety, sleep, and mood disorders.^[14] Although the exact mechanism is not fully understood, lavender is thought to modulate GABA similarly to benzodiazepines and possibly affect serotonin, like SSRIs/SNRIs, without the risk of addiction.^[14,15] The chemical constituents in lavender, such as linalool and linalyl acetate, are believed to act on GABAA receptors in the central nervous system, inducing relaxation.^[15] Additionally, lavender can reduce calcium influx through various voltage-operated calcium channels (VOCCs), which may help normalize hyperactive nerve cells and alleviate symptoms like anxiety and racing thoughts.^[16]

Traditionally, herbalists consider American ginseng to be an adaptogen that helps restore balance to the body,^[30] with fatigue reduction being one of the most well-known benefits of this herb. The active ginsenosides found within American ginseng are believed to act on the CNS and possess cortisol-modulating effects, impacting the HPA axis to improve energy, physical and emotional health, and wellbeing.^[31]

Rehmannia has been shown to possess anti-fatigue properties, as confirmed via research conducted in animal models.^[17] It has been noted that an increase in exercise endurance is a powerful representation of rehmannia’s anti-fatigue effect.^[18] The anti-fatigue effects are associated with the ability of rehmannia to reduce the levels of blood lactic acid (BLA) and serum urea nitrogen (SUN), two biochemical markers related to fatigue.^[18] Further research has pointed to the polysaccharide content of rehmannia as the main chemical components related to the anti-fatigue properties.^[18]

American ginseng has shown promise in preclinical studies assessing its impacts on human cognition and mood stabilisation. One clinical trial has shown significant benefit for the use of American ginseng for neurocognitive function and related acute mood state.^[8] In this randomised, double-blind, placebo-controlled, crossover trial 32 healthy young adults aged 18–40 years were assessed for acute mood (calmness), neurocognitive and glycaemic effects upon consuming one of three doses (100, 200, or 400 mg) of American ginseng (standardised to 10.65% ginsenosides). Participants' mood, cognitive function and blood glucose were measured at baseline and 1, 3 and 6 hours following administration. Results demonstrated a significant improvement in working memory (WM) performance associated with American ginseng intake (at all doses), with self-rated calmness increasing following 100 mg of American ginseng at 3 and 6 hours post treatment.^[8] This preliminary study identified American ginseng’s treatment-related improvements in neurocognitive performance and association of increased calmness in healthy young adults.^[8]

A follow-up study aimed to partially replicate the aforementioned double-blind, placebo-controlled, balanced, cross-over design, evaluated American ginseng‘s impact upon mood and WM.^[19] This study aimed to investigate whether the beneficial effects of American ginseng extended to healthy middle-aged individuals. Fifty-two healthy volunteers aged 40-60 years received either 200 mg of American ginseng or placebo to evaluate cognitive performance and impact on mood.^[19] A noted improvement in WM performance and mood stabilisation was yet again achieved. It was noted that as cognitive improvements are most consistently found in WM measures, a plausible explanation could relate to a ginsenoside-mediated augmentation of the dopaminergic neurotransmitter system.^[19] Therefore, American ginseng has the ability to improve cognitive performance on WM and stabilise mood, which may assist in areas of mental fatigue and support nervous exhaustion.

Wild oats extract contains a range of bioactive components that have been shown to enhance and improve cognitive performance in humans.^[12] The effects of a single dose green oat extract (GOE) were assessed in a double-blind, placebo-controlled, counterbalanced cross-over study. Healthy adults aged 40–65 years who self-reported their memory had declined with age received a single dose of either 800 or 1600 mg GOE or placebo, with the treatments repeated twice for each participant. Cognitive function was assessed with a range of computerised tasks measuring attention, spatial/working/episodic memory, and executive function at baseline and at 1, 2.5, 4, and 6 hours post-dose.^[12] The results showed that 800 mg GOE increased the speed of performance across post-dose assessments on a global measure including data from all of the timed tasks. Performance improved in a variety of mental tasks with decreased thinking time and overall completion time.^[12] These results confirm the beneficial effects of GOE on cognitive performance.

Lavender’s anxiolytic properties have been postulated to have a positive effect on generalised anxiety disorder (GAD). A controlled clinical study was performed to evaluate the efficiency of 6 weeks’ intake of an oral lavender capsule preparation, compared with Lorazepam (benzodiazepine) in adults with GAD. The primary target variable was the change in the Hamilton Anxiety Rating Scale (HAM-A) as an objective measurement of the severity of anxiety between baseline at week 6. During the active treatment period, the mean HAM-A total score decreased clearly and to a similar extent in both groups (by 11.3 + 6.7 points (45%) in the lavender group and by 11.6 + 6.6 points (46%) in the Lorazepam group), from a baseline of 25 + 4 points in both groups. The HAM-A subscores for somatic anxiety and psychic anxiety also decreased clearly and to a similar extent in both groups. The results note that oral lavender effectively ameliorates generalised anxiety, comparable to Lorazepam.^[15] This research indicates that lavender may deliver a gentle, yet effective treatment option as an alternative to conventional anxiolytic drugs.

Lavender has also been demonstrated to be efficacious in sub-syndromal and syndromal anxiety disorders and concommitant depressive symptoms.^[16] In this study, 318 adult out-patients with mixed anxiety and depressive disorder (MADD) according to international classification of disease (ICD-10) criteria (a total score ≥18 points on the HAM-A, and at least moderately severe anxious and depressed mood), were randomised and received 80 mg/d lavender or placebo for a scheduled period of 70 days. Primary outcomes measured were total score changes in the HAM-A and Montgomery Åsberg Depression Rating Scale (MADRS) between baseline and treatment end. The HAM-A total score decreased by 10.8 ± 9.6 points for patients in the lavender group compared with 8.4 ± 8.9 points for placebo (treatment group difference: p<0.01). Total score decreases of 9.2 ± 9.9 and 6.1 ± 7.6 points respectively, were observed for the MADRS (p<0.001).^[47] Compared to placebo, the patients treated with lavender had better overall clinical outcomes for anxiety and depressive symptoms, and showed more pronounced improvements of impaired daily living skills and health related quality of life.^[16] This study strengthens the use of lavender as efficacious and safe in the treatment of mixed anxiety and depression symptoms.

Disclaimer: In the interest of supporting Healthcare Practitioners, all safety information provided at the time of publishing is in accordance with Natural Medicine Database (NATMED PRO), renowned for its professional monographs which include a thorough assessment of safety, warnings, and adverse effects.

For further information on specific interactions with medications, please contact Clinical Support on 1800 777 648, or via email, anz_clinicalsupport@metagenics.com

• Possibly unsafe/insufficient reliable information available; avoid using.[21]

• Contraindicated with Warfarin (Coumadin); avoid this combination.[21]

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21. Natural Medicines Database. AusDi; 2024. Accessed September 20, 2024. https://ausdi.hcn.com.au/