Adrenotone® Technical Data

Herbs and Nutrients That May Assist

Withania
Withania somnifera, root dry
Siberian ginseng
Eleutherococcus senticosus, root dry
Golden root
Rhodiola rosea, root dry
Liquorice
Glycyrrhiza glabra, root dry
Korean ginseng
Panax ginseng, root dry
Tyrosine

Actions

  • Modulates the HPA axis in response to stress
  • Supports performance under stress
  • Anti-inflammatory

Clinical Applications

  • Improves physical and mental performance under stress
  • Chronic fatigue
  • Fatigue associated with mood disorders

Herbal and Nutritional Support for Adrenal Health

Adaptogenic herbs like withania, Siberian ginseng, rhodiola, liquorice, and Korean ginseng, along with the amino acid tyrosine, can support health during mental and physical stress.[1] Clinical trials show these adaptogens can reduce fatigue, maintain cognitive performance, and improve mood, especially in those with chronic fatigue or mood disorders.[2-6]

Background Technical Information


The HPA Axis

The stress response, regulated by the HPA axis, involves the hypothalamus releasing corticotropin-releasing hormone (CRH) in response to stress.[7] This triggers the pituitary gland to secrete adrenocorticotropic hormone (ACTH), prompting the adrenal glands to produce cortisol.[7] Cortisol binds to brain receptors, creating a feedback loop that reduces CRH release (Figure 1).[7,8]

Figure 1: The HPA axis.[8]

This response helps in ‘fight or flight’ situations by increasing blood volume, pressure, and glucose levels while suppressing immune activation.[9] In chronic stress, the body fails to adapt, leading to HPA axis dysfunction and impaired stress response.[10]

Resolving a Dysfunctional Stress Response

HPA axis dysfunction can lead to fatigue, mood disorders, impaired cognition, and immune issues due to an irregular cortisol response.[10] Supporting HPA axis recovery is crucial for better health outcomes. Adaptogens help by enhancing the body’s ability to adapt to stress, providing a normalizing and protective effect that boosts mental and physical performance.[1] They also share structural similarities with natural stress-related chemicals, improving their interaction with receptors.[11]

Actions

Modulates the HPA axis in Response to Stress

Adaptogens like withania, Siberian ginseng, rhodiola, Korean ginseng, liquorice, and tyrosine enhance adaptation to stress through various pathways. Studies show they regulate key genes in stress response pathways and affect human neuroglial cells, which link the bloodstream and brain.[12] These adaptogens modulate HPA axis mediators, such as CRH and urocortin, to protect against stress and regulate cortisol production.[12]

In vivo studies show Siberian ginseng stimulates neuropeptide Y (NPY) release, which improves stress-related behaviour and is linked to HPA axis regulation.[13] Low NPY levels are associated with stress disorders.[14] NPY activity depends on tyrosine and also up-regulates heat shock protein (HSP) 70, promoting stress resistance.[15] Both Siberian ginseng and rhodiola increase HSP 70, enhancing stress protection across various body systems.[11]

Supports Performance Under Stress

Adaptogens help maintain energy production under stress by modulating neuroendocrine activity and nitric oxide (NO) levels. Siberian ginseng, withania, and liquorice can reduce NO and nitric oxide synthase (i-NOS) activity, improving cellular energy production.[1,15-18] Rhodiola and Siberian ginseng contain phenolic compounds similar to catecholamines, enhancing cognitive performance.[11] Liquorice and Korean ginseng have compounds similar to corticosteroids and cortisol, respectively.[10,11] Tyrosine supports neurotransmitter synthesis, aiding cognitive function.[19]

Anti-inflammatory

Adaptogens like withania, Siberian ginseng, rhodiola, liquorice, and Korean ginseng help modulate inflammation, which can drive HPA axis dysfunction.[20] Chronic inflammation increases cortisol circulation via cytokine-driven activation of 11β-HSD1, raising the risk of HPA axis dysfunction due to prolonged cortisol exposure and suppressed ACTH activity.[21]

Systemic inflammation also generates reactive oxygen species (ROS), damaging cell structures and impairing cellular function under stress.[10,11] Adaptogens mitigate inflammation and oxidative stress, enhancing HPA axis activity. Withania reduces inflammatory proteins like nuclear factor kappa B (NFκB), tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6).[22] Ginsenosides in Siberian and Korean ginseng modulate NFκB activity and have antioxidant effects.[23] Rhodiola and liquorice reduce COX-2 pathways and downstream inflammatory mediators.[24,25]

Clinical Applications

Improves Physical and Mental Performance Under Stress

Clinical evidence shows that 600 mg/day of withania extract reduces cortisol and perceived stress in subjects after four and eight weeks(p<0.05).[27] In athletes, the same dose over 12 weeks significantly improved cardiorespiratory endurance, blood oxygen levels (p<0.0001), and overall health(p<0.05).[27] Additionally, the same dose of withania increased muscle strength and size with resistance training(p<0.05), while preserving muscle quality under intense activity(p<0.03).[26]

In another study, 18 subjects taking rhodiola (3 mg/kg) an hour before a six-mile cycling trial showed improved performance, decreased heart rate, (p<0.037) and reduced perceived exertion compared to placebo (p<0.04).[28] Another study with 40 students taking 1,100 mg/day of rhodiola for 20 days reported a 50% improvement in psychomotor function, including accuracy and speed(p<0.01).[29]

In two double-blind, placebo-controlled studies, young adults taking 200 mg/day of standardized Korean ginseng showed improved accuracy and performance on mental tasks with reduced fatigue (p<0.05).[30] Another study with 19 participants using different potencies of Korean ginseng (960 mg/day, 160 mg/day, or placebo) over three 14-day cycles found dose-dependent reductions in cortisol, less muscle damage, and better HPA axis responses to physical stress.[31] Additionally, a study with 2 g/day of Korean ginseng for four weeks significantly decreased fatigue severity (p<0.033).[32]

Short-term doses of 100 mg/kg/day of tyrosine reduce performance impairments from cold stress and hypoxia, and improve cognitive task performance under noise stress.[33,34] For instance, 2 g/day of tyrosine for five days during combat training significantly improved short-term memory and perceptual motor skills, reducing stress and fatigue(p<0.05).[35]

Chronic Fatigue

Stress-related disorders like chronic fatigue syndrome (CFS), myalgic encephalitis (ME), and fibromyalgia (FMS) share symptoms such as fatigue, pain, and disturbed sleep, worsened by stress and inflammation.[36,37] While fatigue typically resolves with rest, HPA axis dysfunction plays a major role in CFS, preventing proper stress adaptation.[36]

Evidence shows no structural abnormalities in the HPA axis in CFS, indicating a functional cause.[38] Meta-analysis data reveals an underactive stress response with altered cortisol rhythms and output, suggesting HPA dysfunction in CFS.[36]

Adaptogens, particularly rhodiola, offer unique benefits for chronic fatigue syndrome (CFS) by increasing stress resilience and reducing inflammation.[2] Rhodiola supplementation (400 mg/day) in 100 subjects over eight weeks significantly improved fatigue, physical activity, cognitive function, sleep quality, and overall quality of life (p<0.0001). It also reduced perceived stress by 41.8%, enhancing work performance and social interactions (p<0.0001).

Positive outcomes have been observed in 90 CFS subjects taking 1 g/day and 2 g/day of Korean ginseng for four weeks. Both dosages improved CFS symptoms, but only 2 g/day significantly reduced fatigue severity compared to placebo(p<0.01).[3] In another study, 30 cancer patients with chronic fatigue took 800 mg/day of Korean ginseng for one month. After two weeks, 87% reported improvements in fatigue and wellbeing (p<0.013), appetite (p<0.0097), and sleep (p<0.004).[39] Global fatigue scores improved in 63% of patients, with a median improvement of five points.

Fatigue Associated with Mood Disorders

Dysregulation of the HPA axis is a key feature of mood disorders, linked to stress-induced changes in brain neural networks.[40] This includes an enlarged, hyper-responsive amygdala and dendritic shrinkage in the hippocampus and prefrontal cortex, which regulate the HPA axis and stress response.[41] These changes can lead to low mood and are associated with chronic stress.[42]

Rhodiola was found to be effective in the treatment of mild to moderate depression in 91 individuals receiving dosages of either 340 mg/d and 680 mg/d of rhodiola or placebo, administered for six weeks.[4] Overall depression, together with insomnia, emotional instability and somatisation, improved significantly with rhodiola compared to placebo (p<0.0001).[4]

In major depressive disorder, 3 g/day of Korean ginseng over eight weeks significantly improved symptoms, including fatigue and overall disease severity.[5] Subjects reported a notable decrease in depressive symptoms (p<0.05) and improvements in symptom severity (p<0.001), indicating Korean ginseng’s efficacy as an adjunct treatment for mood disorders.[5]

Summary of ingredients

Ingredient and Dose Range

Duration of Studies

Sample of Results

Korean ginseng

200 mg/d – 400 mg/d

Single dose

Korean ginseng improved self-reported ratings of calmness and cognitive performance in a dose-dependent manner (p<0.05).[43]

Korean ginseng

200 mg/d

Single dose

Korean ginseng demonstrated improvements in accuracy and performance of mental tasks, as well as reduced mental fatigue following a battery of cognitively demanding tasks (p<0.05).[30,44]

Withania

600 mg/d

4 – 8 weeks

Withania significantly reduced scores for perceived stress (p<0.05) and decreased serum cortisol levels (p<0.05) among chronically stressed individuals.[27]

Withania

600 mg/d

8 weeks

Withania improved physical performance under stress, increasing muscle strength and size when combined with resistance training (p<0.05) and preserving muscle quality under intense physical activity (p<0.03).[26]

Withania

600 mg/d

12 weeks

Withania administered to 50 athletes significantly improved physical performance under stress (measured by cardiorespiratory endurance and increased blood oxygen levels [p<0.0001]), as well as enhancing scores for physical, psychological and social health (p<0.05).[45]

Rhodiola

340 mg/d – 680 mg/d

6 weeks

Treatment with rhodiola significantly improved mood scores, emotional instability and somatisation in patients experiencing mood disturbances.[4]

Rhodiola

400 mg/d

8 weeks

Rhodiola significantly improved fatigue, physical activity levels, work performance, social and family life experiences, as well as reducing cognitive impairment in fatigued individuals (p<0.0001). There was also a decrease in perceived stress by 41.8% (p<0.0001).[2]

Safety Information

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

Pregnancy and Lactation

  • Unsafe/insufficient reliable information available; avoid using.[46]

Contraindications

  • None listed.[46]

    References

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