Metagenics
Adrenotone
Adrenal Support, HPA Regulation
Supports stress resilience, cognitive function and energy production via modulating the hypothalamic-pituitary-adrenal axis.
- Helps withstand physical and mental stress
- Improves physical and mental performance under stress
- Reduces fatigue associated mood disorders
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BENEFITS
CLINICALLY PROVEN;
Supports adaptability to stress by regulating gene keys
Improve physical performance under stress
Enhances cognitive performace under stress
Alleviates Fatigue, and fatigue associated mood disroders
Anti-inflammatory
ADAPTOGENIC
In vitro analysis of the molecular mechanisms purported by withania, Siberian ginseng and rhodiola indicates that of 3,516 genes regulated by these adaptogens, 75 genes encode key regulatory functions within adaptive stress response signalling pathways.[18] Further, these effects were observed in human neuroglial cells that comprise 90% of the central nervous system (CNS), serving as a link between the bloodstream and neurons within the brain.
All three herbs effectively modulated the expression of upstream mediators of the HPA axis, such as CRH and urocortin (UCN) involved in the regulation of allostasis. Specifically, withania and Siberian ginseng were shown to up-regulate the expression of stress protective and neuroprotective neurohormone UCN, whilst down-regulating cortisol inducing CRH, highlighting their modulatory effects upon HPA axis activity. Similarly, rhodiola has been observed to exert a stress protective effect via inhibition of CRH, resulting in a modulatory effect on cortisol production.[19]
..In vitro analysis of the molecular mechanisms purported by withania, Siberian ginseng and rhodiola indicates that of 3,516 genes regulated by these adaptogens, 75 genes encode key regulatory functions within adaptive stress response signalling pathways…
Further, in vivo studies reveal Siberian ginseng has been demonstrated to stimulate the release of neuropeptide Y (NPY) within neuroglial cells associated with HPA axis regulation.[20] Clinical studies support the role of NPY in improving behavioural performance under stress, whilst lower levels of NPY have been associated with dysfunctional HPA axis conditions including post-traumatic stress disorder, major depressive disorder and childhood stress[21]; indicating the role of NPY in a maladaptive stress response. In addition, NPY activity is also dependant on tyrosine availability as the structure of NPY is composed of the five tyrosine residues.
Further, NPY also up-regulates molecular chaperone, heat shock protein (HSP) 70 associated with promoting stress resistance.[22] HSP 70 plays a key role in eliminating stress-induced irregularities in DNA proteins, which interfere with normal cellular function, and increasing immune surveillance and innate immunity.[23] Both Siberian ginseng and rhodiola were also shown to increase HSP 70, giving rise to adaptive and stress protective effects via the CNS and sympathetic, endocrine, immune cardiovascular and gastrointestinal systems.[24]
SUPPORTS PERFORMANCE UNDER STRESS
Performance-enhancing mechanisms of adaptogens are associated with maintaining energy production under stress, in addition to modulating neuroendocrine activity. Energy production is altered under stressful conditions due to the effects of nitric oxide (NO) and nitric oxide synthase (i-NOS) activity, which supresses the production of adenosine triphosphate (ATP) under aerobic conditions.[25] Siberian ginseng has been shown to modulate inflammation-induced NO and i-NOS activity in animal models,[26] whilst withania[27] and liquorice[28],[29] can moderate levels of NO and i-NOS in models of cellular stress. As such, these adaptogens ameliorate the impacts of stress upon impaired cellular energy production.
Further, rhodiola and Siberian ginseng contain relatively high levels of phenolic compounds, namely lignans, phenylpropane or phenylethane derivatives.[30] These compounds are structurally related to catecholamines including adrenaline and dopamine, and exert similar effects in enhancing cognitive performance. The liquorice constituent, glycyrrhizin is structurally similar to corticosteroids,[31] while Korean ginseng contains relatively large amounts of tetracyclic triterpenoids structurally similar to cortisol.[32] Tyrosine is the core amino acid involved in the synthesis of dopamine and noradrenaline, and provides essential neurotransmitter support for cognitive enhancement.[33] Similarities between endogenous neurochemicals and plant compounds may partly explain the attenuating effects of nutritional and botanical extracts on performance in HPA axis dysfunction as well as enhanced physical and cognitive performance.
ANTI-INFLAMMATORY
In addition to the aforementioned mechanisms of action, withania, Siberian ginseng, rhodiola, liquorice and Korean ginseng also modulate inflammation as a driver of HPA axis dysfunction.[34] Chronic inflammation can increase circulation of cortisol from its inactivated form, cortisone, via cytokine-driven activation of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) illustrated in Figure 4.[35] Accordingly, systemic inflammation increases the risk of HPA axis dysfunction due to effects of long-term cortisol exposure resulting in supressed ACTH activity.[36]
Moreover, systemic inflammation is also associated with the generation of reactive oxygen species (ROS) which leads to damage of cell structures, triggering senescence and apoptosis; negatively impacting overall cellular respiration and function under stress.[38] Adaptogens regulate the effects of inflammation and subsequent oxidative stress as part of enhancing functional HPA axis activity.
The anti-inflammatory activity of withania has been shown in vivo to reduce the expression of inflammatory transcription proteins including nuclear factor kappa B (NFκB) and downstream inflammatory mediators such as tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6).[39] Further, ginsenosides, an important constituent in both Siberian ginseng and Korean ginseng, have been revealed to reduce inflammation via the modulation of NFκB activity, in addition to their antioxidant effects.[40] Similarly, constituents within rhodiola[41] and liquorice[42] demonstrate significant anti-inflammatory activity by reducing cyclooxygenase-2 (COX-2) pathways and subsequent downstream inflammatory mediators. Collectively, adaptogenic compounds offer a myriad of effects that aid and regulate HPA axis activity, providing therapeutic aid for a functional stress response.
ENHANCES COGNITIVE PERFORMANCE UNDER STRESS
Originally recorded in Ayurvedic texts, withania is considered to exert anti-stress effects which modify HPA axis activity.[43] Clinical evidence supports the actions of withania in reducing cortisol, whilst enhancing aerobic output and strength. For example, 52 subjects experiencing chronic stress received 600 mg/d of withania extract and demonstrated reductions in perceived stress after four and eight weeks of supplementation (p<0.05), as well as a reduction in serum cortisol levels after four and eight weeks (p<0.05).[44] Moreover, the same dose of withania administered to 50 athletes for 12 weeks significantly improved cardiorespiratory endurance by increasing blood oxygen levels at peak athletic performance (p<0.0001), in addition to enhancing quality of physical, psychological and social health (p<0.05).[45] Furthermore, 600 mg/d of withania extract in 57 subjects was also shown to increase muscle strength and size with resistance training (p<0.05), while preserving muscle quality under intense physical activity (p<0.03).[46] Such results highlight the efficacy of withania in optimising patient outcomes.
Research also substantiates the use of rhodiola for enhancing performance under stress. For instance, 18 subjects receiving rhodiola (3 mg/kg of body weight) an hour before a six-mile cycling time trial, significantly enhanced performance compared to placebo. Specifically, rhodiola decreased heart rate and increased performance speed in the treatment group (p<0.037). The subjects further reported a reduction in perceived exertion with herbal supplementation (p<0.04), supporting the effects of rhodiola in enhancing physical performance.[47] Further, performance-enhancing benefits were also reported in a study of 40 students receiving 1,100 mg/d of rhodiola for 20 days prior to undergoing experimental physical and mental testing. Outcomes of the study revealed a 50% improvement in psychomotor function including accuracy and speed (p<0.01).[48] As indicated, evidence endorses the effects of rhodiola in promoting cognitive outcomes under mentally and physically stressful circumstances.
..Rhodiola supplementation was shown to enhance associative thinking, short-term memory, calculation and concentration, and speed of audio-visual perception within a two week period..
Evidence indicates the efficacy of Korean ginseng for enhancing cognitive ability under stress. In two double-blind, placebo-controlled studies, young adults who received 200 mg/d of standardised Korean ginseng preparation completed a battery of cognitively demanding tasks to assess endurance. Effects within the treatment group revealed improved accuracy and performance of mental tasks with reduced mental fatigue (p<0.05).[49],[50]Comparably, in a double-blind, placebo-controlled study, 19 participants completed three 14-day treatment cycles with different potencies of Korean ginseng (high: 960 mg/d; low: 160 mg/d; or placebo) separated by a one week washout period. At the end of each treatment phase, participants underwent intense resistance exercise with screening for cortisol at 0, 30, 60 minutes and 24 hours after exercise.
Results of supplementation demonstrated dose-dependent reductions in circulating cortisol, reduced muscle damage and improved HPA axis responses to physical stress.[51] Furthermore, in a study evaluating 2 g/d of Korean ginseng or placebo for four weeks, treatment with Korean ginseng significantly decreased fatigue severity in a healthy population (p<0.033),[52] supporting the role of Korean ginseng in stress adaptation.
Acute stress relief and enhanced performance as a result of tyrosine supplementation has been demonstrated in human subjects. Short-term doses of tyrosine at 100 mg/kg/d have been found to reduce the effects of acute stress leading to performance impairments associated with cold stress and hypoxia.[53]Moreover, tyrosine supplementation was shown to improve performance of cognitive tasks with noise stress.[54] For example, daily administration of 2 g/d tyrosine for five days during a combat training course resulted in significantly improved short-term memory and perceptual motor skills, reducing the associated physical and psychosocial stress and fatigue (p<0.05).[55]
As such, selected adaptogenic extracts optimise and sustain performance through protecting and modulating HPA axis function, and mounting evidence continues to highlight the role of withania, rhodiola, Korean ginseng and tyrosine in improving performance under stress.
ALLEVIATES FATIGUE
Stress-related disorders such as chronic fatigue syndrome (CFS), myalgic encephalitis (ME), and fibromyalgia (FMS) share several symptoms such as fatigue, pain, and disturbed sleep, which are exacerbated by stress[56] and inflammation.[57] Usually, fatigue remits after overcoming stressors with sufficient time to rest and recover. However, existing evidence indicates HPA axis dysfunction plays a major role in CFS, failing to achieve allostasis and adapt to stress (Figure 5).[58]
Scientific evidence indicates that there is an absence of structural abnormalities within the HPA axis in CFS, suggesting such symptoms are likely due to a functional cause.[60]Interestingly, meta-analysis data demonstrates clear evidence for an underactive stress response with adverse changes in cortisol rhythmicity and general cortisol output measures in these patients,[61] suggesting that some HPA dysfunction is likely to be implicated within CFS.
Adaptogens offer unique benefits in CFS by increasing resilience to stress. Further, the anti-inflammatory effects of adaptogens help to mitigate the effects of inflammation in CFS. Rhodiola supplementation has been found to improve several aspects of CFS including stress symptoms, unrefreshing sleep, quality of life, low mood and poor concentration; with excellent tolerability.[62] Researchers looking at the effects of 400 mg/d of rhodiola in 100 subjects with CFS over eight weeks found significant improvement in fatigue, in addition to improved physical activity levels, reduced cognitive impairment and enhanced sleep p<0.0001 (Figure 6).[63] Rhodiola supplementation further improved in work performance as well as social and family life experiences, reducing perceived stress by 41.8% (p<0.0001). Such data substantiates the use of rhodiola in supporting stress resilience and enhancing quality of life for patients with CFS.
Similarly, positive outcomes have also been demonstrated in 90 CFS subjects receiving 1 g/d and 2 g/d of Korean ginseng or placebo for four weeks. Clinical scores of CFS symptoms were significantly improved by both dosages of Korean ginseng, however only the 2 g/d significantly reduced the severity of fatigue compared with placebo (p<0.01).[65] In an additional study in patients experiencing chronic fatigue due to cancer treatment, 30 patients received 800 mg/d dose of Korean ginseng for one month and were assessed for adverse effects of cancer treatment, chronic fatigue and global symptom evaluation.[66] Results revealed that 87% of participants experienced improvements in fatigue and wellbeing (p<0.013), appetite (p<0.0097) and sleep (p<0.004) after just two weeks of supplementation. Further, global scores of fatigue (measured on a scale of 0 to 7) improved in 63% of patients, with a median improvement of five points. Further, physical and psychological distress scores were decreased by Korean ginseng in cancer patients (Figure 7), indicating the effects of adaptogen supplementation on supporting overall perceived stress during illness.[67]
As such, the therapeutic benefits of adaptogenic compounds aid patients experiencing chronic fatigue and help to mitigate additional condition-related stress. Moreover, the effects of adaptogens in enhancing energy and stress resilience, reducing inflammation, and enhancing sleep and mood, offers support to restore a functional allostatic response to stress.
ALLEVIATES FATIGUE ASSOCIATED MOOD DISORDERS
Dysregulation of the HPA axis is one of the most prominent neurobiological features of mood disorders,[69]and is associated with stress-induced remodelling of neural networks within the brain. This results in an enlarged and hyper-responsive amygdala, in addition to dendritic shrinkage, affecting both the hippocampus and the prefrontal cortex; two key areas that regulate the activity of the HPA axis and the stress response.[70] Such physiological changes may manifest with low mood, and are further correlated with chronic stress.[71] In this context, therapeutic effects of herbal extracts have been shown to assist in ameliorating symptoms related to mood disorders and chronic stress-induced fatigue.
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. Overall depression, together with insomnia, emotional instability and somatisation, improved significantly with rhodiola compared to placebo (p<0.0001)(Figure 8).[72]
In cases of major depressive disorder, Korean ginseng has been demonstrated to significantly improve symptoms at a dose of 3 g/d over eight weeks.[74] Several validated assessment tools were utilised in this study to analyse the effects of treatment on 10 depressive symptoms, including fatigue and global disease severity. After eight weeks, subjects reported a significant decrease in depressive symptoms including fatigue (p<0.05), alongside significant improvements in symptom severity (p<0.001). These results suggest that Korean ginseng is efficacious as an adjuvant treatment for patients experiencing mood disorders.
Evidence-based botanical and nutritional compounds exert a broad range of mechanisms that ultimately facilitate an allostatic stress response in a range of clinical presentations. Collectively, withania, Siberian ginseng, rhodiola, liquorice, Korean ginseng and tyrosine can offer acute relief from stress and further aid and protect healthy HPA axis function; thereby supporting patients with fatigue, impaired performance and low mood.
INGREDIENTS
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DIRECTIONS
Adults:
Take 1 tablet three times daily with food
EVIDENCE
References
[1] Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009 Sep;4(3):198-219. PMID: 19500070
[2] Lekomtseva Y, Zhukova I, Wacker A. Rhodiola rosea in subjects with prolonged or chronic fatigue symptoms: results of an open-label clinical trial. Complement Med Res. 2017;24(1):46-52. doi: 10.1159/000457918.
[3] Kim HG, Cho JH, Yoo SR, Lee JS, Han JM, Lee NH, et al. Antifatigue effects of Panax ginseng CA Meyer: a randomised, double-blind, placebo-controlled trial. PLoS One. 2013 Apr 17;8(4):e61271.
[4] Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmström C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-8.
[5] Jeong HG, Ko YH, Oh SY, Han C, Kim T, Joe SH. Effect of Korean red ginseng as an adjuvant treatment for women with residual symptoms of major depression. Asia Pac Psychiatry. 2015 Sep;7(3):330-6. doi: 10.1111/appy.12169.
[6] Head KA, Kelly GS. Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety, and restless sleep. Altern Med Rev. 2009;14(2):114-140.
[7] Edwards LD, Heyman AH, Swidan S. Hypocortisolism: An evidence-based review. Integrative Medicine. 2011;10(4):26-33.
[8] Hyman SE. How adversity gets under the skin. Nat Neurosci. 2009 Mar;12(3):241-3.
[9] McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol. 2008 Apr 7;583(2-3):174-85. doi: 10.1016/j.ejphar.2007.11.071
[10] McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol. 2008 Apr 7;583(2-3):174-85. doi: 10.1016/j.ejphar.2007.11.071
[11] Guilliams TG. The role of stress and the HPA axis in chronic disease management. Stevens Point, WI: Point Institute; 2015 p. 21.
[12] Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009 Sep;4(3):198-219. PMID: 19500070
[13] Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. doi: 10.1111/nyas.13399
[14] Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. doi: 10.1111/nyas.13399
[15] Guilliams TG. The role of stress and the HPA axis in chronic disease management. Stevens Point, WI: Point Institute; 2015 p. 21.
[16] Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals (Basel). 2010 Jan 19;3(1):188-224 doi: 10.3390/ph3010188
[17] Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals (Basel). 2010 Jan 19;3(1):188-224 doi: 10.3390/ph3010188
[18] Panossian A, Seo EJ, Efferth T. Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology. Phytomedicine. 2018 Sep 20. 50(1) 257-284. doi: 10.1016/j.phymed.2018.09.204
[19] Panossian A, Seo EJ, Efferth T. Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology. Phytomedicine. 2018 Sep 20. 50(1) 257-284. doi: 10.1016/j.phymed.2018.09.204
[20] Asea A, Kaur P, Panossian A, Wikman KG. Evaluation of molecular chaperons Hsp72 and neuropeptide Y as characteristic markers of adaptogenic activity of plant extracts. Phytomedicine. 2013 Nov 15;20(14):1323-9. doi:10.1016/j.phymed.2013.07.001.
[21] Kautz M, Charney DS, Murrough JW. Neuropeptide Y, resilience, and PTSD therapeutics. Neurosci Lett. 2017 May 10;649:164-169. doi:10.1016/j.neulet.2016.11.061.
[22] Asea A, Kaur P, Panossian A, Wikman KG. Evaluation of molecular chaperons Hsp72 and neuropeptide Y as characteristic markers of adaptogenic activity of plant extracts. Phytomedicine. 2013 Nov 15;20(14):1323-9. doi:10.1016/j.phymed.2013.07.001.
[23] Panossian A, Wikman G, Kaur P, Asea A. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine. 2009 Jun;16(6-7):617-22. doi: 10.1016/j.phymed.2008.12.003.
[24] Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. doi: 10.1111/nyas.13399
[25] Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009 Sep;4(3):198-219.
[26] Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009 Sep;4(3):198-219.
[27] Devkar ST, Kandhare AD, Zanwar AA, Jagtap SD, Katyare SS, Bodhankar SL et al. Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS. Pharm Biol. 2016 Nov;54(11):2394-2403.
[28] Li K, Ji S, Song W, Kuang Y, Lin Y, Tang S et al. Glycybridins A-K, Bioactive Phenolic Compounds from Glycyrrhiza glabra. J Nat Prod. 2017 Feb 24;80(2):334-346. doi: 10.1021/acs.jnatprod.6b00783.
[29] Yehuda I, Madar Z, Leikin-Frenkel A, Tamir S. Glabridin, an isoflavan from licorice root, downregulates iNOS expression and activity under high-glucose stress and inflammation. Mol Nutr Food Res. 2015 Jun;59(6):1041-52. doi: 10.1002/mnfr.201400876.
[30] Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. doi: 10.1111/nyas.13399
[31] Guilliams TG. The role of stress and the HPA axis in chronic disease management. Stevens Point, WI: Point Institute; 2015 p. 119.
[32] Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. doi: 10.1111/nyas.13399
[33] Coull N, Chrismas B, Watson P, Horsfall R, Taylor L. Tyrosine Ingestion and Its Effects on Cognitive and Physical Performance in the Heat. Med Sci Sports Exerc. 2016 Feb;48(2):277-86. doi: 10.1249/MSS.0000000000000757
[34] Morris G, Anderson G, Maes M. Hypothalamic-pituitary-adrenal hypofunction in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) as a consequence of activated immune-inflammatory and oxidative and nitrosative pathways. Mol Neurobiol. 2017 Nov;54(9):6806-6819.
[35] Straub RH, Cutolo M. Glucocorticoids and chronic inflammation. Rheumatology. 2016 Nov 17;55. doi:10.1093/rheumatology/kew348
[36] Guilliams TG. The role of stress and the HPA axis in chronic disease management. Stevens Point, WI: Point Institute; 2015 p. 21.
[37] Straub RH, Cutolo M. Glucocorticoids and chronic inflammation. Rheumatology. 2016 Nov 17;55. doi:10.1093/rheumatology/kew348
[38] Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017 Aug;1401(1):49-64. doi: 10.1111/nyas.13399
[39] Gupta M, Kaur G. Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study. J Neuroinflammation. 2016 Aug 22;13(1):193. doi: 10.1186/s12974-016-0650-3
[40] Kim HJ, Kim P, Shin CY. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J Ginseng Res. 2013 Mar;37(1):8-29.
[41] Bawa AS, Khanum F. Anti‐inflammatory activity of Rhodiola rosea–“a second‐generation adaptogen”. Phytotherapy Research. 2009 Aug;23(8):1099-102.
[42] Yu JY, Ha JY, Kim KM, Jung YS, Jung JC, Oh S. Anti-Inflammatory activities of licorice extract and its active compounds, glycyrrhizic acid, liquiritin and liquiritigenin, in BV2 cells and mice liver. Molecules. 2015 Jul 20;20(7):13041-54.
[43] Wankhede S, Langade D, Joshi K, Sinha SR, Bhattacharyya S. Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. Journal of the International Society of Sports Nutrition. 2015 Nov 25;12(1):43.
[44] Choudhary D, Bhattacharyya S, Joshi K. Body weight management in adults under chronic stress through treatment with ashwagandha root extract: a double-blind, randomized, placebo-controlled trial. J Evid Based Complementary Altern Med. 2017 Jan;22(1):96-106. doi:10.1177/2156587216641830.
[45] Choudhary B, Shetty A, Langade DG. Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults. Ayu. 2015 Jan;36(1):63.
[46] Wankhede S, Langade D, Joshi K, Sinha SR, Bhattacharyya S. Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. Journal of the International Society of Sports Nutrition. 2015 Nov 25;12(1):43.
[47] Noreen EE, Buckley JG, Lewis SL, Brandauer J, Stuempfle KJ. The effects of an acute dose of Rhodiola rosea on endurance exercise performance. The Journal of Strength & Conditioning Research. 2013 Mar 1;27(3):839-47.
[48] Spasov AA, Wikman GK, Mandrikov VB, Mironova IA, Neumoin VV. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine. 2000;7(2):85-9.
[49] Reay JL, Kennedy DO, Scholey AB. Effects of Panax ginseng, consumed with and without glucose, on blood glucose levels and cognitive performance during sustained 'mentally demanding' tasks. J Psychopharmacol 2006;20(6):771-81.
[50] Reay JL, Kennedy DO, Scholey AB. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J Psychopharmacol 2005;19(4):357-65.
[51] Flanagan SD, DuPont WH, Caldwell LK, Hardesty VH, Barnhart EC, Beeler MK, et al. The Effects of a Korean Ginseng, GINST15, on Hypo-Pituitary-Adrenal and Oxidative Activity Induced by Intense Work Stress. J Med Food. 2018 Jan;21(1):104-112. doi: 10.1089/jmf.2017.0071.
[52] Lee N, Lee SH, Yoo HR, Yoo HS. Anti-fatigue effects of enzyme-modified ginseng extract: a randomized, double-blind, placebo-controlled trial. The Journal of Alternative and Complementary Medicine. 2016 Nov 1;22(11):859-64.
[53] Banderet LE, Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull. 1989 Apr;22(4):759-62.
[54] Deijen JB, Orlebeke JF. Effect of tyrosine on cognitive function and blood pressure under stress. Brain Res Bull. 1994;33(3):319-23.
[55] Deijen JB, Wientjes CJ, Vullinghs HF, Cloin PA, Langefeld JJ. Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Res Bull. 1999 Jan 15;48(2):203-9.
[56] Strahler J, Skoluda N, Rohleder N, Nater UM. Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue. Neurosci Biobehav Rev. 2016 Sep;68:298-318. doi: 10.1016/j.neubiorev.2016.05.008.
[57] Milrad SF, Hall DL, Jutagir DR, Lattie EG, Ironson GH, Wohlgemuth W et al. Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women. Journal of neuroimmunology. 2017 Feb 15;303:43-50.
[58] Strahler J, Skoluda N, Rohleder N, Nater UM. Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue. Neurosci Biobehav Rev. 2016 Sep;68:298-318. doi: 10.1016/j.neubiorev.2016.05.008.
[59] Strahler J, Skoluda N, Rohleder N, Nater UM. Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue. Neurosci Biobehav Rev. 2016 Sep;68:298-318. doi:10.1016/j.neubiorev.2016.05.008.
[60] Tanriverdi F, Karaca Z, Unluhizarci K, Kelestimur F. The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome. Stress. 2007 Mar;10(1):13-25.
[61] Strahler J, Skoluda N, Rohleder N, Nater UM. Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue. Neurosci Biobehav Rev. 2016 Sep;68:298-318. doi: 10.1016/j.neubiorev.2016.05.008.
[62] Lekomtseva Y, Zhukova I, Wacker A. Rhodiola rosea in subjects with prolonged or chronic fatigue symptoms: results of an open-label clinical trial. Complement Med Res. 2017;24(1):46-52. doi: 10.1159/000457918.
[63] Lekomtseva Y, Zhukova I, Wacker A. Rhodiola rosea in subjects with prolonged or chronic fatigue symptoms: results of an open-label clinical trial. Complement Med Res. 2017;24(1):46-52. doi: 10.1159/000457918.
[64] Lekomtseva Y, Zhukova I, Wacker A. Rhodiola rosea in subjects with prolonged or chronic fatigue symptoms: results of an open-label clinical trial. Complement Med Res. 2017;24(1):46-52. doi: 10.1159/000457918.
[65] Kim HG, Cho JH, Yoo SR, Lee JS, Han JM, Lee NH, et al. Antifatigue effects of Panax ginseng CA Meyer: a randomised, double-blind, placebo-controlled trial. PLoS One. 2013 Apr 17;8(4):e61271.
[66] Yennurajalingam S, Reddy A, Tannir NM, Chisholm GB, Lee RT, Lopez G, et al. High-dose Asian ginseng (Panax ginseng) for cancer-related fatigue: a preliminary report. Integrative Cancer Therapies. 2015 Sep;14(5):419-27.
[67] Yennurajalingam S, Reddy A, Tannir NM, Chisholm GB, Lee RT, Lopez G, et al. High-dose Asian ginseng (Panax ginseng) for cancer-related fatigue: a preliminary report. Integrative Cancer Therapies. 2015 Sep;14(5):419-27.
[68] Yennurajalingam S, Reddy A, Tannir NM, Chisholm GB, Lee RT, Lopez G, et al. High-dose Asian ginseng (Panax ginseng) for cancer-related fatigue: a preliminary report. Integrative Cancer Therapies. 2015 Sep;14(5):419-27.
[69] Aihara M, Ida I, Yuuki N, Oshima A, Kumano H, Takahashi K et al. HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic/paralimbic regions.Psychiatry Res. 2007 Aug 15;155(3):245-56.
[70] Roozendaal B, McEwen BS, Chattarji S. Stress, memory and the amygdala. Nat Rev Neurosci. 2009 Jun;10(6):423-33.
[71] Fleshner M, Frank M, Maier SF. Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders. Neuropsychopharmacology. 2017 Jan;42(1):36-45. doi: 10.1038/npp.2016.125.
[72] Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmström C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-8.
[73] Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmström C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-8.
[74] Jeong HG, Ko YH, Oh SY, Han C, Kim T, Joe SH. Effect of Korean red ginseng as an adjuvant treatment for women with residual symptoms of major depression. Asia Pac Psychiatry. 2015 Sep;7(3):330-6. doi: 10.1111/appy.12169.
[75] European Medicines Agency. Community herbal monograph on Rhodiola rosea L., rhizome et radix. 2012 [cited 2018 Jan 2]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2012/05/WC500127863.pdf. p. 3.
[76] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 834-843.
[77] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1192-4.
[78] Fetrow CW, Avila JR. Professionals handbook of complementary and alternative medicines. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2004. p. 58-60.
[79] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[80] Baek JH, Nierenberg AA, Kinrys G. Clinical applications of herbal medicines for anxiety and insomnia; targeting patients with bipolar disorder. Australian & New Zealand Journal of Psychiatry. 2014;48(8):705-715.
[81] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 834-843.
[82] Health Canada [Internet]. Rholiola [updated 2017 Oct 23; cited 2018 Jan 2]. Available from: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=rhodiol&lang=eng.
[83] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[84] Dasgupta A, Peterson A, Wells A, Actor JK. Effect of Indian Ayurvedic medicine Ashwagandha on measurement of serum digoxin and 11 commonly monitored drugs using immunoassays: study of protein binding and interaction with Digibind. Arch Pathol Lab Med. 2007 Aug;131(8):1298-303.
[85] Dasgupta A, Tso G, Wells A. Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin immunoassay. J Clin Lab Anal. 2008;22(4):295-301. doi:10.1002/jcla.20252.
[86] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 329.
[87] Siberian ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 26]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[88] Prescribers’ Digital Reference [Internet]. Digoxin – drug summary. [2017; cited 2017 Oct 25]. Available from: http://www.pdr.net/drug-summary/Digoxin-digoxin-724.
[89] Drugs.com [Internet]. Digoxin tablets [2017; cited 2017 Oct 24]. Available from: https://www.drugs.com/pro/digoxin-tablets.html.
[90] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. CYP450 drug interactions. [2017 Oct 1; cited 2017 Oct 26]. Available from: http://www.emims.com.au/Australia/pub/latestIssue/Clinical%20Resources/CYP450%20Drug%20Interactions. Subscription required to view.
[91] Drugbank. Digoxin [Internet]. 2017 [cited Oct 26]. Available from: https://www.drugbank.ca/drugs/DB00390.
[92] Yu L. Quality and bioequivalence standards for narrow therapeutic index drugs [2011; cited 2017 May 18]. Available from: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/ucm292676.pdf.
[93] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[94] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[95] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[96] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[97] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A. Food Chem. 2012;135:2307-2312.
[98] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[99] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[100] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[101] Fetrow CW, Avila JR. Professionals handbook of complementary and alternative medicines. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2004. p. 501.
[102] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[103] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 452.
[104] Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Human Hyperten. 2017;31:699-707.
[105] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[106] Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Human Hyperten. 2017;31:699-707.
[107] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 329.
[108] Siberian ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 26]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[109] Stargrove MB, Treasure J, McKee DL. Herb, nutrient, and drug interactions. St Louis (MO): Mosby Elsevier; 2010. p. 698-705.
[110] Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Human Hyperten. 2017;31:699-707.
[111] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[112] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[113] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[114] Fetrow CW, Avila JR. Professionals handbook of complementary and alternative medicines. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2004. p. 501.
[115] Drugbank [Internet]. Amiodarone [2017; cited 2017 Oct 26]. Available from: https://www.drugbank.ca/drugs/DB01118.
[116] Prescribers’ Digital Reference [Internet]. Amiodarone hydrochloride – drug summary [2017; cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Cordarone-amiodarone-hydrochloride-997.
[117] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. CYP450 drug interactions. [2017 Oct 1; cited 2017 Oct 20]. Available from: http://www.emims.com.au/Australia/pub/latestIssue/Clinical%20Resources/CYP450%20Drug%20Interactions. Subscription required to view.
[118] Prescribers’ Digital Reference. Amiodarone hydrochloride – drug summary [Internet]. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Cordarone-amiodarone-hydrochloride-997.
[119] Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr. 2012 Jun 1;35(3):85.
[120] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[121] Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016;72:295-300.
[122] Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Biol. 2016;54(12):3249-56.
[123] Spanakis M, Vizirianakis IS, Batzias G, Niopas I. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacol. 2013;91(1-2):12-6.
[124] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[125] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[126] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[127] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[128] DynaMed Plus [Internet]. Serotonin Syndrome [updated 2016 Sep 30; cited 2018 Jan 2]. Available from: http://www.dynamed.com/topics/dmp~AN~T193270/Serotonin-syndrome.
[129] Stargrove MB, Treasure J, McKee DL. Herb, nutrient, and drug interactions. St Louis (MO): Mosby Elsevier; 2010. p. 698-705.
[130] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 834-843.
[131] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[132] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 834-843.
[133] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[134] McGovern E, McDonnell TJ. Herbal medicine – sets the heart racing! Irish Med J. 2010;103(7):219.
[135] Maniscalco I, Toffol E, Giupponi G, Conca A. The interaction of Rhodiola rosea and antidepressants. A case reports. Neuropsychiatrie. 2015;29(1):40-9.
[136] McGovern E, McDonnell TJ. Herbal medicine – sets the heart racing! Irish Med J. 2010;103(7):219.
[137] Maniscalco I, Toffol E, Giupponi G, Conca A. The interaction of Rhodiola rosea and antidepressants. A case reports. Neuropsychiatrie. 2015;29(1):40-9.
[138] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[139] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 619-23.
[140] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1022-1030.
[141] Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Human Hyperten. 2017;31:699-707.
[142] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[143] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 643-59.
[144] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[145] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 643-59.
[146] Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced neurotoxicity. Cancer Lett. 2000 Jan 1;148(1):9-17.
[147] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[148] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1192-4.
[149] Harkness R, Bratman S. Mosby’s handbook of drug-herb and drug-supplement interactions. St Louis (MO): Mosby Inc.; 2003. p. 204-5.
[150] Prescribers’ Digital Reference. Etravirine – drug summery [Internet]. 2017 [cited 2017 Oct 23]. Available from: http://www.pdr.net/drug-summary/Intelence-etravirine-1241.
[151] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. Etravirine – Full PI. [2017 Mar 1; cited 2017 Oct 23]. Available from: http://www.emims.com.au/Australia/drug/info/Intelence/Intelence?type=full. Subscription required to view.
[152] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[153] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[154] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[155] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[156] Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016;72:295-300.
[157] Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Biol. 2016;54(12):3249-56.
[158] Spanakis M, Vizirianakis IS, Batzias G, Niopas I. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacol. 2013;91(1-2):12-6.
[159] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[160] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[161] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[162] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[163] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 643-59.
[164] Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Human Hyperten. 2017;31:699-707.
[165] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[166] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 464.
[167] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 329.
[168] Kraft K, Kelber O, Schmidt M. Eleutherococccus senticosus root in hypertensive patients: an unjustified contradiction unmasked? J Altern Comp Med. 2014 may;20(5):A8-A81.
[169] Mills S, Bone K. The essential guide to herbal safety. Philadelphia (PA): Elsevier/Churchill Livingstone; 2005. p. 578.
[170] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 619-23.
[171] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[172] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 619-23.
[173] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[174] Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett. 2000 Jan 1;148(1):9-17.
[175] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[176] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1192-4.
[177] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 462.
[178] Siberian ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 26]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[179] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[180] Skidmore-Roth L. Mosby’s handbook of herbs & natural supplements. 4th ed. St Louis (MO): Mosby Elsevier; 2010. p. 296.
[181] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1022-1030.
[182] Tyrosine. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Oct 16; cited 2018 Jul 16]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1037. Subscription required to view.
[183] Tyrosine. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Oct 16; cited 2018 Jul 16]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1037. Subscription required to view.
[184] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[185] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1192-4.
[186] Fetrow CW, Avila JR. Professionals handbook of complementary and alternative medicines. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2004. p. 58-60.
[187] Takahashi N, Inui N, Morita H, Takeuchi K, Uchida S, Watanabe H, et al. Effect of thyroid hormone on the activity of CYP3A enzyme in humans. J Clin Pharmacol. 2010 Jan;50(1):88-93.
[188] Kim HI, Kim HT, Kim H, Kim YN, Jang HW, Chung JH, et al. Effect of rifampin on thyroid function test in patients on levothyroxine medication. PLoS ONE. 2017;12(1):e0169775.
[189] Drugs.com. Levothyroxine [Internet]. 2017 [updated 2017 Apr; cited 2017 Oct 4]. Available from: https://www.drugs.com/pro/levothyroxine.html.
[190] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[191] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[192] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[193] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[194] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[195] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[196] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 453.
[197] Drugbank [Internet]. Phenobarbital [2017; cited 2017 Oct 24]. Available from: https://www.drugbank.ca/drugs/DB01174.
[198] Prescribers’ Digital Reference. Phenobarbital – drug summary. 2017 [cited 2017 Oct 24]. Available from: http://www.pdr.net/drug-summary/Phenobarbital-Tablets--15-mg--30-mg--60-mg--100-mg--phenobarbital-861.
[199] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. CYP450 drug interactions. [2017 Oct 1; cited 2017 Oct 26]. Available from: http://www.emims.com.au/Australia/pub/latestIssue/Clinical%20Resources/CYP450%20Drug%20Interactions. Subscription required to view.
[200] Yu L. Quality and bioequivalence standards for narrow therapeutic index drugs [2011; cited 2017 May 18]. Available from: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/ucm292676.pdf.
[201] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[202] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[203] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[204] Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016;72:295-300.
[205] Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Biol. 2016;54(12):3249-56.
[206] Spanakis M, Vizirianakis IS, Batzias G, Niopas I. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacol. 2013;91(1-2):12-6.
[207] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[208] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[209] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[210] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[211] Prescribers’ Digital Reference. Phenytoin – drug summary [Internet]. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Dilantin-Capsules-phenytoin-sodium-1813.
[212] Drugbank. Phenytoin [Internet]. 2017 [cited Oct 26]. Available from: https://www.drugbank.ca/drugs/DB00252.
[213] Yu L. Quality and bioequivalence standards for narrow therapeutic index drugs. 2011 [cited 2017 May 18]. Available from: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/ucm292676.pdf.
[214] Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr. 2012 Jun 1;35(3):85.
[215] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[216] Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016;72:295-300.
[217] Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Biol. 2016;54(12):3249-56.
[218] Spanakis M, Vizirianakis IS, Batzias G, Niopas I. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacol. 2013;91(1-2):12-6.
[219] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[220] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[221] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[222] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[223] Prescribers’ Digital Reference. Rifampin – drug summary. 2017 [cited 2017 Oct 26]. Available from: https://www.drugbank.ca/drugs/DB01045.
[224] Drugbank. Rifampicin [Internet]. 2017 [cited 2017 Oct 26]. Available from: https://www.drugbank.ca/drugs/DB01182.
[225] Lucas C, Donovan P. Medications: Just a repeat: When drug monitoring is indicated. Australian Family Physician. 2013 Jan;42(1/2):18.
[226] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[227] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[228] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[229] Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016;72:295-300.
[230] Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Biol. 2016;54(12):3249-56.
[231] Spanakis M, Vizirianakis IS, Batzias G, Niopas I. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacol. 2013;91(1-2):12-6.
[232] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[233] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[234] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[235] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[236] Prescribers’ Digital Reference. Warfarin – drug summary [Internet]. 2017 [cited 2017 Oct 26]. Available from: http://www.pdr.net/drug-summary/Warfarin-warfarin-sodium-3720.
[237] Drugbank. Warfarin [Internet]. 2017 [cited 2017 Oct 26]. Available from: https://www.drugbank.ca/drugs/DB00682.
[238] Yu L. Quality and bioequivalence standards for narrow therapeutic index drugs. 2011 [cited 2017 May 18]. Available from: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/ucm292676.pdf.
[239] Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr. 2012 Jun 1;35(3):85.
[240] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[241] Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016;72:295-300.
[242] Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Biol. 2016;54(12):3249-56.
[243] Spanakis M, Vizirianakis IS, Batzias G, Niopas I. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacol. 2013;91(1-2):12-6.
[244] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[245] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[246] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[247] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[248] Siberian ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 26]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[249] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 463.
[250] Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part 2): drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Med. 2012;78:1490-1514.
[251] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[252] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 619-23.
[253] Siberian ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 26]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[254] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 464.
[255] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[256] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 619-23.
[257] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[258] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[259] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[260] Hou Y-C, Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[261] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[262] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[263] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[264] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[265] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 835.
[266] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 462.
[267] Siberian ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 26]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[268] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[269] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[270] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1192-4.
[271] Harkness R, Bratman S. Mosby’s handbook of drug-herb and drug-supplement interactions. St Louis (MO): Mosby Inc.; 2003. p. 204-5.
[272] Prescribers’ Digital Reference. Carbamazepine – drug summary [Internet]. 2017 [cited 2017 Oct 26]. Available from: http://www.pdr.net/drug-summary/Carbamazepine-carbamazepine-3186.
[273] Drugbank. Carbamazepine [Internet]. 2017 [cited 2017 Oct 26]. Available from: https://www.drugbank.ca/drugs/DB00564.
[274] Lucas C, Donovan P. Medications:'Just a repeat': When drug monitoring is indicated. Australian family physician. 2013 Jan;42(1/2):18.
[275] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[276] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[277] Hou Y-C, Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[278] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[279] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[280] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1022-1030.
[281] Stargrove MB, Treasure J, McKee DL. Herb, nutrient, and drug interactions. St Louis (MO): Mosby Elsevier; 2010. p. 698-705.
[282] Prescribers’ Digital Reference. Cyclosporine – drug summary [Internet]. 2017 [cited 2017 Oct 26]. Available from: http://www.pdr.net/drug-summary/Gengraf-Capsules-cyclosporine-11.
[283] Drugbank. Cyclosporine [Internet]. 2017 [cited 2017 Oct 26]. Available from: https://www.drugbank.ca/drugs/DB00091.
[284] Yu L. Quality and bioequivalence standards for narrow therapeutic index drugs [2011; cited 2017 May 18]. Available from: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/ucm292676.pdf.
[285] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[286] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[287] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[288] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[289] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[290] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[291] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[292] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[293] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[294] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[295] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[296] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[297] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[298] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[299] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[300] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[301] Hou Y-C, Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[302] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[303] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[304] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. CYP450 drug interactions. [2017 Oct 1; cited 2017 Oct 26]. Available from: http://www.emims.com.au/Australia/pub/latestIssue/Clinical%20Resources/CYP450%20Drug%20Interactions. Subscription required to view.
[305] Prescribers’ Digital Reference. Disopyramide phosphate – drug summary [Internet]. 2017 [cited 2017 Oct 26]. Available from: http://www.pdr.net/drug-summary/Norpace-Norpace-CR-disopyramide-phosphate-1182.
[306] Sagawa K, Mohri K, Shimada S, Shimizu M, Muramatsu J. Disopyramide concentrations in human plasma and saliva: comparison of disopyramide concentrations in saliva and plasma unbound concentrations. E J Clin Pharmacol. 1996;65.
[307] Pharmacists Pharma Journal. List of narrow therapeutic range drugs [Internet]. 2017 [cited 2017 Oct 19]. Available from: http://www.pharmacistspharmajournal.org/2010/12/list-of-narrow-therapeutic-range-drugs.html.
[308] Tamargo J, Le Heuzey J-Y, Mabo P. Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide. Eu J Clin Pharmacol. 2015;71(5):549-567.
[309] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[310] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[311] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[312] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[313] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[314] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[315] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[316] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[317] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[318] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[319] Prescribers’ Digital Reference. Ethosuximide – drug summary [Internet]. 2017 [cited 2017 Oct 26]. Available from: http://www.pdr.net/drug-summary/Zarontin-Capsules-ethosuximide-1844.
[320] Drugbank. Ethosuximide [Internet]. 2017 [cited 2017 Oct 26]. Available from: https://www.drugbank.ca/drugs/DB00390.
[321] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[322] Pope ND. Generic substitution of narrow therapeutic index drugs. US Pharm. 2009;34(6)(Generic Drug Review suppl):12-19.
[323] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[324] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[325] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[326] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[327] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[328] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[329] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[330] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[331] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[332] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[333] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[334] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[335] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[336] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1192-4.
[337] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[338] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[339] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[340] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[341] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[342] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[343] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[344] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[345] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[346] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[347] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[348] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[349] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[350] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[351] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[352] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[353] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[354] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[355] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[356] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[357] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[358] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[359] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[360] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[361] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[362] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[363] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[364] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[365] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[366] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[367] Licorice. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Jun 4; cited 2018 Oct 25]. Available from: http://www.naturaldatabase.com. Subscription required to view
[368] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[369] Skidmore-Roth L. Mosby’s handbook of herbs & natural supplements. 4th ed. St Louis (MO): Mosby Elsevier; 2010. p. 396.
[370] Mills S, Bone K. The essential guide to herbal safety. Philadelphia (PA): Elsevier/Churchill Livingstone; 2005. p. 433-6.
[371] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. CYP450 drug interactions. [2017 Oct 1; cited 2017 Oct 26]. Available from: http://www.emims.com.au/Australia/pub/latestIssue/Clinical%20Resources/CYP450%20Drug%20Interactions. Subscription required to view.
[372] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[373] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[374] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[375] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[376] Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Human Hyperten. 2017;31:699-707.
[377] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[378] Drugbank. Propafenone [Internet]. 2017 [cited Oct 20]. Available from: https://www.drugbank.ca/drugs/DB01182.
[379] Prescribers’ Digital Reference. Propafenone hydrochloride – drug summary. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/rythmol?druglabelid=223.
[380] Tamargo J, Le Heuzey JY, Mabo P. Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide. Eur J Clin Pharmacol. 2015 May;71(5):549-67.
[381] Prescribers’ Digital Reference. Propafenone hydrochloride – drug summary [Internet]. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/rythmol?druglabelid=223.
[382] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[383] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[384] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[385] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[386] Prescribers’ Digital Reference. Quinidine sulfate – drug summary. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Quinidine-Sulfate-Tablets-quinidine-sulfate-3103.3451.
[387] MIMS Australia. CYP450 drug interactions [Internet]. 2016 [cited 2017 Oct 26]. Available from: http://www.emims.com.au/Australia/pub/latestIssue/Clinical%20Resources/CYP450%20Drug%20Interactions.
[388] Tamargo J, Le Heuzey JY, Mabo P. Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide. Eur J Clin Pharmacol. 2015 May;71(5):549-67.
[389] NPS Medicinewise [Internet]. Therapeutic drug monitoring [1997; cited 2017 Oct 19]. Available from: https://www.nps.org.au/australian-prescriber/articles/therapeutic-drug-monitoring.
[390] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[391] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[392] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[393] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[394] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[395] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[396] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[397] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[398] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[399] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[400] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[401] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[402] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[403] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[404] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[405] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[406] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[407] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[408] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[409] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[410] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[411] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[412] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. Sirolimus – Full PI. [2017 Oct 1; cited 2017 Oct 19]. Available from: http://www.emims.com.au/Australia/drug/info/Rapamune/Rapamune?type=full. Subscription required to view.
[413] Prescribers’ digital reference. Sirolimus – drug summary. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Rapamune-sirolimus-2097.4085.
[414] Drugs.com [Internet]. Sirolimus dosage [2017; cited 2017 Oct 19]. Available from: https://www.drugs.com/dosage/sirolimus.html.
[415] NPS Medicinewise [Internet]. Therapeutic drug monitoring: which drugs, why, when and how to do it [2008; cited 2017 Oct 19]. Available from: https://www.nps.org.au/australian-prescriber/articles/therapeutic-drug-monitoring-which-drugs-why-when-and-how-to-do-it.
[416] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[417] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[418] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[419] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[420] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[421] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[422] Mills S, Bone K. The essential guide to herbal safety. Philadelphia (PA): Elsevier/Churchill Livingstone; 2005. p. 434.
[423] Panax ginseng. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Aug 16; cited 2018 Oct 29]. Available from: http://www.naturaldatabase.com. Subscription required to view.
[424] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[425] MIMs Online [Internet]. St Leonards (NSW): MIMs Australia Pty Ltd.; 2017. Tacrolimus – Full PI. [2016 Nov 1; cited 2017 Oct 19]. Available from: http://www.emims.com.au/Australia/drug/info/Advagraf%20XL/Advagraf%20XL?type=full#Interactions. Subscription required to view.
[426] Prescribers’ Digital Reference. Tacrolimus – drug summary. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Prograf-tacrolimus-1331.3795.
[427] Tamargo J, Le Heuzey JY, Mabo P. Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide. Eur J Clin Pharmacol. 2015 May;71(5):549-67.
[428] Food and Drug Administration. Draft guidance on tacrolimus [Internet]. 2012 [cited 2017 Oct 19]. Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM181006.pdf.
[429] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[430] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[431] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[432] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[433] Fetrow CW, Avila JR. Professionals handbook of complementary and alternative medicines. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2004. p. 500.
[434] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[435] Prescribers’ Digital Reference. Theophylline – drug summary [Internet]. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Theophylline-Extended-Release-Tablets--100-mg--200-mg--300-mg--450-mg--theophylline-3337.
[436] Drugbank. Theophylline [Internet]. 2017 [cited 2017 Oct 20]. Available from: https://www.drugbank.ca/drugs/DB00277.
[437] Lucas C, Donovan P. Medications: 'Just a repeat': When drug monitoring is indicated. Aust Fam Physic. 2013 Jan;42(1/2):18.
[438] Liang BA, Mackey TK, Lovett KM. Illegal “no prescription” internet access to narrow therapeutic index drugs. Clinical Therapeutics. 2013 May 31;35(5):694-700.
[439] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[440] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[441] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[442] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[443] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[444] Tyrosine. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Oct 16; cited 2018 Jul 16]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1037. Subscription required to view.
[445] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1022-1030.
[446] Stolbach A, Paziana K, Heverling H, Pham P. A review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015;11:326-341.
[447] Justesen US. Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral therapy. Basic Clin Pharmacol Toxicol. 2006;98(1):20-31.
[448] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[449] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney: Elsevier/Churchill Livingstone; 2015. p. 841.
[450] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[451] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[452] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[453] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[454] MIMS Australia. CYP450 drug interactions [Internet]. 2016 [cited 2017 Oct 4]. Available from: http://www.emims.com.au/Australia/pub/latestIssue/Clinical%20Resources/CYP450%20Drug%20Interactions.
[455] Prescribers’ Digital Reference. Valproate sodium – drug summary [Internet]. 2017 [cited 2017 Oct 20]. Available from: http://www.pdr.net/drug-summary/Depacon-valproate-sodium-2015.
[456] Pharmacists Pharma Journal. List of narrow therapeutic range drugs [Internet]. 2010 [cited 2017 Sep 4]. Available from: http://www.pharmacistspharmajournal.org/2010/12/list-of-narrow-therapeutic-range-drugs.html.
[457] Tu J-H, He Y-J, Chen Y, Fan L, Zhang W, Tan Z-R, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010;66:805-810.
[458] Hou Y-C. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP3A. Food Chem. 2012;135:2307-2312.
[459] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 654.
[460] Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique “guide drug” of traditional Chinese medicine: a review of its role in drug interactions. J Ethnopharmacol. 2013;15:781-90.
[461] Ashwagandha. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Oct 31; cited 2018 Mar 7]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=953. Subscription required to view.
[462] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 1192-4.
[463] Fetrow CW, Avila JR. Professionals handbook of complementary and alternative medicines. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2004. p. 58-60.
[464] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 418.
[465] Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th ed. Vol 2. Sydney (AU): Elsevier/Churchill Livingstone; 2015. p. 655.
[466] Rhodiola. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2017 Dec 14; cited 2018 Jan 2]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=883.
[467] Skidmore-Roth L. Mosby’s handbook of herbs & natural supplements. 4th ed. St Louis (MO): Mosby Elsevier; 2010. p. 566.
[468] Mills S, Bone K. The essential guide to herbal safety. Philadelphia (PA): Elsevier/Churchill Livingstone; 2005. p. 578.
[469] Tyrosine. In: Natural Medicines Comprehensive Database [database on the Internet]. Stockton (CA): Therapeutic Research Faculty; 1995-2018 [updated 2018 Oct 16; cited 2018 Jul 16]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1037. subscription required to view.
[470] Gardner Z, McGuffin M. Botanical safety handbook. 2nd ed. Boca Raton (FL): CRC Press; 2013. p. 418.
[471] Mills S, Bone K. The essential guide to herbal safety. Philadelphia (PA): Elsevier/Churchill Livingstone; 2005. p. 499.
WARNINGS
Contraindications
Allergies and sensitivities: Avoid in individuals with known allergy or hypersensitivity to rhodiola and/or members of the Crassulaceae family,[75],[76] or sensitivities to the Solanaceae family of plants.[77],[78]
Bipolar disorder: Rhodiola has been shown to increase central serotonin levels and exert an antidepressant effect.[79] There are concerns that rhodiola may be stimulating and increase the risk of cycling;[80] therefore, the use of rhodiola in patients with bipolar is considered contraindicated.[81],[82]
Digoxin: Use cautiously in patients on this medication, and only under medical supervision. Avoid long-term use (e.g. more than two weeks).[83]
In vitro studies have found that withania may interfere with serum digoxin measurements by the fluorescent polarization immunoassay and other assays.[84],[85]A case report associated Siberian ginseng with increased digoxin levels, however it is possible the herb was adulterated with a common substitute Periploca sepium, which contains cardiac glycosides.[86],[87]
This cardiac glycoside drug is metabolised by P-glycoprotein[88],[89] and cytochrome P450 3A4,[90],[91] and has a narrow therapeutic range.[92],[93] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[94],[95] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[96] with animal evidence showing the whole herb to exert a similar effect,[97] which theoretically could change the drug’s therapeutic effect.[98],[99]
Due to the potassium-decreasing activity of liquorice, the combination of liquorice with digoxin may increase the risk of cardiac/digitalis toxicity due to potassium loss.[100],[101]Korean ginseng contains glycosides with structural similarities to digoxin, which may interfere with some serum digoxin measurements. No case reports have been identified of an actual interaction; however as these glycosides may falsely alter digoxin results, be aware of possible false changes to serum digoxin measurements.[102],[103]
Heart disease: Avoid use in patients with heart disease due to glycyrrhizin content in this product.[104]
The mineralocorticoid effects of liquorice can worsen congestive heart failure and fluid retention, as well as increase the risk of arrhythmias.[105],[106]Siberian ginseng has been reported to cause tachycardia, pericardial pain, palpitations and insomnia in patients with atherosclerosis or rheumatic heart disease.[107],[108]
Hereditary tyrosinemia type 1 (HT1): HT1 is a severe metabolic disease associated with tyrosine catabolism. Individuals that have this disorder should avoid tyrosine.[109]
Hypokalemia: The mineralocorticoid effects of liquorice (attributed to the glycyrrhizin[110]) can decrease serum potassium levels and exacerbate hypokalemia,[111],[112] therefore avoid use in patients with this condition.
Renal (kidney) disease/insufficiency: The mineralocorticoid effects of liquorice may worsen renal function.[113] Avoid use in patients with severe kidney insufficiency/renal disease.[114]
Moderate Level Cautions
Amiodarone: This class III anti-arrhythmic drug is metabolised by P-glycoprotein[115],[116] and cytochromes P450 2C9 and 3A4,[117],[118] and has a narrow therapeutic range.[119],[120] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein and both human and animal evidence has shown rhodiola can inhibit the activity of CYP2C9;[121],[122],[123] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[124] with animal evidence showing the whole herb to exert a similar effect,[125] which theoretically may change the drug’s therapeutic effect.[126],[127] Use cautiously in patients on this medication and monitor for symptom changes.
Antidepressant medications: Use cautiously in patients on these medications and monitor closely for symptom changes or symptoms of additive effects or symptoms of Serotonin Syndrome (e.g. agitation, confusion, tachycardia, dilated pupils, incoordination, muscle rigidity, myoclonus, shivering, fever, tremor, and diarrhoea).[128],[129] Avoid in patients with hypertension, monitor blood pressure in all other patients and only combine under professional supervision.Rhodiola may inhibit monoamine oxidase (MAO)-A[130] and MAO-B,[131] which therefore may theoretically interact with MAO-inhibitor (MAOI) antidepressants.[132]
In case reports, patients taking the selective serotonin reuptake inhibitors (SSRIs) escitalopram[133],[134] and paroxetine with rhodiola experienced symptoms associated with Serotonin Syndrome[135] (including tachycardia,[136] vegetative syndrome, restlessness and trembling).[137] Whilst case reports can be difficult to determine, these reports are in line with the known serotonergic effect of rhodiola.
Theoretically, Korean ginseng may interfere with MAOI therapy. Case reports have identified concomitant use of Korean ginseng with phenelzine to cause symptoms of mania, insomnia, tremors and headaches.[138],[139]
Concurrent use of tyrosine with monoamine oxidase inhibitors (MOAIs), tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and/or selective noradrenaline reuptake inhibitors (SNRIs), may result in enhanced antidepressant effects and/or elevated blood pressure.[140]
Antihypertensive medication: The mineralocorticoid effects of liquorice can increase blood pressure (attributed to the glycyrrhizin[141]).[142] Use with caution in patients taking antihypertensive drugs, and not for prolonged periods (e.g. more than two weeks),[143] as liquorice may alter the efficacy of the antihypertensive medication.
Corticosteroids: Concurrent use of liquorice with oral corticosteroids may potentiate the effects of the corticosteroids. When used in combination, liquorice may increase potassium loss and increase the risk of potassium depletion. Use with caution in patients on acute or chronic corticosteroid therapy.[144],[145]
Cyclophosphamide: Withania may decrease the effectiveness of immunosuppressant therapy because of its immunostimulating effects (withania stimulates stem-cell proliferation). There is preliminary evidence that withania might decrease immunosuppression caused by cyclophosphamide.[146],[147],[148],[149] Caution should be exercised with patients taking cyclophosphamide and withania concurrently.
Etravirine:This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by P-glycoprotein and cytochromes P450 2C9[150],[151] and 3A4, and has a narrow therapeutic range.[152],[153] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein[154],[155] and both human and animal evidence has shown Rhodiola can inhibit the activity of CYP2C9.[156],[157],[158] Additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[159] with animal evidence showing the whole herb to exert a similar effect,[160] which theoretically may change the drug’s therapeutic effect.[161],[162] Use cautiously in patients on this medication and monitor for symptom changes.
Hypertension: Use with caution in patients with hypertension, and not for prolonged periods (e.g. more than two weeks).[163]The mineralocorticoid effects of liquorice can increase blood pressure (attributed to the glycyrrhizin).[164],[165]
Conflicting data exists regarding the safety of Siberian ginseng in patients with hypertension.[166],[167] The recent consensus is that the caution for regarding hypertension is unfounded, with Siberian ginseng potentially displaying antihypertensive activity.[168],[169] Given the current data, negative effects are unlikely from Siberian ginseng; however, it is suitable to monitor patients due to this.
Conflicting data exists regarding the safety of Korean ginseng in patients with hypertension. Whilst ginseng has been associated with the development of hypertension, the opposite has been demonstrated with some studies showing Korean ginseng may moderately decrease blood pressure in patients.[170],[171]
Hypotension: Whilst conflicting information exists regarding Korean ginseng’s effect on blood pressure, studies show it may moderately decrease blood pressure in patients.[172],[173] Monitor blood pressure changes in patients with hypotension.
Immunosuppressants: Use with caution in patients on immunosuppressants (e.g. cyclosporine, tacrolimus, sirolimus, daclizumab, azathioprine, prednisone and other corticosteroids).Withania may decrease the effectiveness of immunosuppressant therapy because of its immunostimulating effects (withania stimulates stem-cell proliferation).[174],[175],[176]
Siberian ginseng can modulate the immune system,[177] and therefore may stimulate the immune system which theoretically may interfere with immunosuppressant medications.[178]
Korean ginseng has been shown to modulate the immune system, and therefore may stimulate the immune system which theoretically may interfere with immunosuppressant medications.[179],[180]
Levodopa: L-Dopa competes with tyrosine for brain uptake, therefore concurrent use may decrease effectiveness of Levodopa.[181],[182] Separate doses by at least two hours.[183]
Levothyroxine/Thyroxine: Use cautiously in patients on this medication and monitor for symptom changes.Withania may add to the effects of thyroid medication. An in vivo study reported that daily administration of withania enhanced serum thyroxine concentrations.[184],[185],[186]
This thyroid hormone is a substrate for cytochrome P450 3A4,[187],[188] and has a narrow therapeutic range.[189],[190] Human evidence shows constituents of liquorice induce the activity of this enzyme,[191] with animal evidence showing the whole herb to exert a similar effect,[192] which theoretically may change the drug’s therapeutic effect.[193],[194]
Nifedipine: Korean ginseng has been shown to increase the plasma concentration of this calcium channel blocker in healthy subjects.[195],[196] This may cause an increase in the blood pressure lowing activity of nifedipine, therefore monitor blood pressure in patients if combining.
Phenobarbital (phenobarbitone): This barbiturate is a widely used anti-seizure medication and is metabolised by P-glycoprotein[197] and cytochromes P450 2C9 and 3A4,[198],[199] and has a narrow therapeutic range.[200],[201] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein,[202],[203] and both human and animal evidence has shown rhodiola can inhibit the activity of CYP2C9.[204],[205],[206] Additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[207] with animal evidence showing the whole herb to exert a similar effect,[208] which theoretically may change the drug’s therapeutic effect.[209],[210] Use cautiously in patients on this medication and monitor for symptom changes.
Phenytoin: This anti-epileptic, anticonvulsant and anti-seizure drug is metabolised by cytochromes P450 2C9 and 3A4,[211],[212] and has a narrow therapeutic range.[213],[214],[215] Both human and animal evidence has shown Rhodiola can inhibit the activity of CYP2C9;[216],[217],[218] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[219] with animal evidence showing the whole herb to exert a similar effect,[220] which theoretically may change the drug’s therapeutic effect.[221],[222] Use cautiously in patients on this medication and monitor for symptom changes.
Rifampicin (rifampin): This antibiotic drug is metabolised by P-glycoprotein and cytochromes P450 2C9 and 3A4,[223],[224] and has a narrow therapeutic range.[225],[226] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein[227],[228] and both human and animal evidence has shown Rhodiola can inhibit the activity of CYP2C9.[229],[230],[231] In addition, human evidence shows constituents of liquorice induce the activity of CYP3A4,[232] with animal evidence showing the whole herb to exert a similar effect,[233] which theoretically may change the drug’s therapeutic effect.[234],[235] Use cautiously in patients on this medication and monitor for symptom changes.
Warfarin: This anticoagulant medication is metabolised by cytochromes P450 2C9 and 3A4,[236],[237] and has a narrow therapeutic range.[238],[239],[240] Both human and animal evidence has shown Rhodiola can inhibit the activity of CYP2C9;[241],[242],[243] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[244] with animal evidence showing the whole herb to exert a similar effect,[245] which theoretically may change the drug’s therapeutic effect.[246],[247] Use cautiously in patients on this medication and monitor INR levels.
Low Level Cautions
Anticoagulant/antiplatelet drugs: Increased bleeding is unlikely, however it is suitable to monitor patient for changes.Siberian ginseng may have anticoagulant activity, although mixed results have been seen. Evidence of anticoagulant activity is mainly based on dated animal studies,[248] and recent evidence shows Siberian ginseng in combination with warfarin did not cause significant changes in bleeding times.[249]
Korean ginseng has been reported to possess anticoagulant activity, and case reports have speculated ginseng to reduce warfarin anticoagulation. However, human research suggests Korean ginseng does not affect platelet aggregation, and has no effect on the pharmacodynamics or pharmacokinetics of warfarin.[250],[251],[252]
Antidiabetic drugs: Use with caution and monitor blood glucose levels if combining.
Conflicting information exists regarding Siberian ginseng and its effect on blood glucose. Animal studies have shown Siberian ginseng can have hypoglycaemic effects. However, this has not been observed in humans, and the herb may rather increase postprandial blood glucose levels.[253],[254]Korean ginseng may have hypoglycaemic effects, therefore an additive effect alongside antidiabetic drugs is possible.[255],[256]
Atazanavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[257],[258] Human evidence shows constituents of liquorice induce the activity of this enzyme,[259] with animal evidence showing the whole herb to exert a similar effect,[260] which theoretically may change the drug’s therapeutic effect.[261],[262] Use cautiously in patients on this medication and monitor for symptom changes.
Autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis): Use with caution in patients with autoimmune disease and monitor symptoms.Withania may have immunostimulant effects, which theoretically might exacerbate autoimmune diseases by stimulating immune activity.[263]
There is some evidence from animal and in vitro research from rhodiola in isolation, and human evidence using rhodiola in combination with other herbs, which demonstrates rhodiola may have immunostimulatory effects.[264],[265] Theoretically, rhodiola could therefore exacerbate autoimmune diseases by stimulating disease activity.
Siberian ginseng may have immunostimulant activity,[266] and therefore may exacerbate autoimmune diseases by increasing immune activity.[267]
Korean ginseng may have immunostimulant activity, and therefore may exacerbate autoimmune diseases by increasing immune activity.[268]
Benzodiazepines, barbiturates and CNS depressants: Withania has sedative effects and when taken with barbiturates, additive effects are theoretically possible, leading to increased sedation. A beneficial effect is possible under medical supervision. Observe patients taking withania and these types of medicines concurrently.[269],[270],[271]
Carbamazepine: This anti-epileptic, neurotropic and psychotropic drug is metabolised by cytochrome P450 3A4,[272],[273] and has a narrow therapeutic range.[274],[275] Human evidence shows constituents of liquorice induce the activity of this enzyme,[276] with animal evidence showing the whole herb to exert a similar effect,[277] which theoretically may change the drug’s therapeutic effect.[278],[279] Use cautiously in patients on this medication and monitor for symptom changes.
Central nervous system (CNS) stimulants (amphetamines, dextroamphetamine, methylphenidate e.g. Concerta, Ritalin): Conflicting information exists regarding co-administration of tyrosine with CNS stimulant drugs. Tyrosine is a precursor to a number of neurotransmitters, so it is thought that additive effects may occur,[280] resulting in excessive stimulation. However, tyrosine may enhance dopamine synthesis, therefore reversing or preventing tyrosine depletion caused by amphetamines.[281] Monitor patients closely for symptoms associated with excessive stimulation (e.g. anxiety, difficulty with sleep, impaired concentration and hyperactivity).
Cyclosporine (ciclosporin): This potent immunosuppressant anti-rejection drug is metabolised by P-glycoprotein and cytochrome P450 3A4,[282],[283] and has a narrow therapeutic range.[284],[285] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[286],[287] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[288] with animal evidence showing the whole herb to exert a similar effect,[289] which theoretically may change the drug’s therapeutic effect.[290],[291] Use cautiously in patients on this medication and consult the patient’s specialist if prescribed to manage organ transplant.
Darunavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[292],[293] Human evidence shows constituents of liquorice induce the activity of this enzyme,[294] with animal evidence showing the whole herb to exert a similar effect,[295] which theoretically may change the drug’s therapeutic effect.[296],[297] Use cautiously in patients on this medication and monitor for symptom changes.
Delavirdine: This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[298],[299] Human evidence shows constituents of liquorice induce the activity of this enzyme,[300] with animal evidence showing the whole herb to exert a similar effect,[301] which theoretically may change the drug’s therapeutic effect.[302],[303] Use cautiously in patients on this medication and monitor for symptom changes.
Disopyramide: This class IA anti-arrhythmic drug is metabolised by cytochrome P450 3A4,[304],[305] and has a narrow therapeutic range.[306],[307],[308] Human evidence shows constituents of liquorice induce the activity of this enzyme,[309] with animal evidence showing the whole herb to exert a similar effect,[310] which theoretically may change the drug’s therapeutic effect.[311],[312] Use cautiously in patients on this medication and monitor for symptom changes.
Efavirenz: This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by cytochrome P540 3A4 and has a narrow therapeutic range.[313],[314] Human evidence shows constituents of liquorice induce the activity of this enzyme,[315] with animal evidence showing the whole herb to exert a similar effect,[316] which theoretically may change the drug’s therapeutic effect.[317],[318] Use cautiously in patients on this medication and monitor for symptom changes.
Ethosuximide: This anticonvulsant drug is metabolised by cytochrome P450 3A4,[319],[320] and has a narrow therapeutic range.[321],[322] Human evidence shows constituents of liquorice induce the activity of this enzyme,[323] with animal evidence showing the whole herb to exert a similar effect,[324] which theoretically may change the drug’s therapeutic effect.[325],[326] Use cautiously in patients on this medication and monitor for symptom changes.
Fosamprenavir: This HIV antiretroviral protease inhibitor is metabolised by P-glycoprotein and cytochrome P450 3A4, and has a narrow therapeutic range.[327],[328] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein[329],[330]; additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[331] with animal evidence showing the whole herb to exert a similar effect,[332] which theoretically may change the drug’s therapeutic effect.[333],[334] Use cautiously in patients on this medication and monitor for symptom changes.
Gastric ulcers: Use with caution in people with active stomach (peptic) or duodenal ulcers. Withania may cause gastric irritation.[335],[336] If there is an increase in pain, patients could try taking a demulcent also, or taking the herb with food.
Indinavir: This HIV antiretroviral protease inhibitor is metabolised by P-glycoprotein and cytochrome P450 3A4, and has a narrow therapeutic range.[337],[338] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[339],[340] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[341] with animal evidence showing the whole herb to exert a similar effect,[342] which theoretically may change the drug’s therapeutic effect.[343],[344] Use cautiously in patients on this medication and monitor for symptom changes.
Lopinavir: This HIV antiretroviral protease inhibitor is metabolised by P-glycoprotein and cytochrome P450 3A4, and has a narrow therapeutic range.[345],[346] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[347],[348] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[349] with animal evidence showing the whole herb to exert a similar effect,[350] which theoretically may change the drug’s therapeutic effect.[351],[352] Use cautiously in patients on this medication and monitor for symptom changes.
Nelfinavir: This HIV antiretroviral protease inhibitor is metabolised by P-glycoprotein and cytochrome P450 3A4, and has a narrow therapeutic range.[353],[354] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[355],[356] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[357] with animal evidence showing the whole herb to exert a similar effect,[358] which theoretically may change the drug’s therapeutic effect.[359],[360] Use cautiously in patients on this medication and monitor for symptom changes.
Nevirapine: This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[361],[362] Human evidence shows constituents of liquorice induce the activity of this enzyme,[363] with animal evidence showing the whole herb to exert a similar effect,[364] which theoretically may change the drug’s therapeutic effect.[365],[366] Use cautiously in patients on this medication and monitor for symptom changes.
Oestrogen therapy and/or oestrogen-sensitive conditions: Use with caution alongside oestrogen therapy or in patients with a history of oestrogen-sensitive cancers (e.g. breast, overian, uterine) or conditions such as endometriosis or fibroids.[367],[368]Liquorice may have phytoestrogenic properties, thus exerting a balancing effect on oestrogen levels.[369]
Korean ginseng may have oestrogenic properties.[370]
Oral contraceptive pill (OCP): Use cautiously in patients on this medication, monitor blood pressure and consider alternative contraceptive options whilst combining liquorice with OCP’s.Most OCP’s (e.g. those containing levonorgestrel, ethinyloestradiol, drospirenone) are metabolised by cytochrome P450 3A4.[371] Human evidence shows glycyrrhizin from liquorice can induce the activity of this enzyme,[372] with animal evidence showing the whole herb to exert a similar effect,[373] which theoretically may reduce the drug’s therapeutic effect.[374],[375]
The mineralocorticoid effects of liquorice can increase the risk of side effects from the OCP including hypokalaemia, fluid retention and elevated blood pressure (attributed to the glycyrrhizin[376]).[377]
Propafenone: This class IC anti-arrhythmic drug is metabolised by cytochrome P450 3A4,[378],[379] and has a narrow therapeutic range.[380],[381] Human evidence shows constituents of liquorice induce the activity of this enzyme,[382] with animal evidence showing the whole herb to exert a similar effect,[383] which theoretically may change the drug’s therapeutic effect.[384],[385] Use cautiously in patients on this medication and only under medical supervision.
Quinidine: This anti-malarial and class IA anti-arrhythmic drug is metabolised by P-glycoprotein and cytochrome P450 3A4,[386],[387] and has a narrow therapeutic range.[388],[389] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[390],[391] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[392] with animal evidence showing the whole herb to exert a similar effect,[393] which theoretically may change the drug’s therapeutic effect.[394],[395] Use cautiously in patients on this medication and monitor for symptom changes.
Ritonavir: This HIV antiretroviral protease inhibitor is metabolised by P-glycoprotein and cytochrome P450 3A4, and has a narrow therapeutic range.[396],[397] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[398],[399] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[400] with animal evidence showing the whole herb to exert a similar effect,[401] which theoretically may change the drug’s therapeutic effect.[402],[403] Use cautiously in patients on this medication and monitor for symptom changes.
Saquinavir: This HIV antiretroviral protease inhibitor is metabolised by P-glycoprotein and cytochrome P450 3A4, and has a narrow therapeutic range.[404],[405] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[406],[407] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[408] with animal evidence showing the whole herb to exert a similar effect,[409] which theoretically may change the drug’s therapeutic effect.[410],[411] Use cautiously in patients on this medication and monitor for symptom changes.
Sirolimus (Rapamycin): This immunosuppressant anti-rejection drug is metabolised by P-glycoprotein and cytochrome P450 3A4,[412],[413] and has a narrow therapeutic range.[414],[415] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[416],[417] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[418] with animal evidence showing the whole herb to exert a similar effect,[419] which theoretically may change the drug’s therapeutic effect.[420],[421] Use cautiously in patients on this medication and consult the patient’s specialist if prescribed to manage organ transplantation.
Stimulants: Due to the risk of overstimulation, it is recommended to use with caution when combining Korean ginseng with a high caffeine intake or other stimulants due to an additive effect.[422],[423]
Surgery: Withania has CNS depressant effects. Theoretically, withania might cause additive CNS depression when combined with anesthesia and other medications during and after surgical procedures. Tell patients to discontinue withania at least two weeks before elective surgical procedures.[424]
Tacrolimus: This potent immunosuppressant anti-rejection drug is metabolised by cytochrome P450 3A4,[425],[426] and has a narrow therapeutic range.[427],[428] Human evidence shows constituents of liquorice induce the activity of this enzyme,[429] with animal evidence showing the whole herb to exert a similar effect,[430] which theoretically may change the drug’s therapeutic effect.[431],[432] Use cautiously in patients on this medication and consult the patient’s specialist if prescribed to manage organ transplant.
Testosterone: Liquorice may decrease testosterone levels,[433] however conflicting results exist in clinical trials.[434] Monitor patients for reduction in testosterone levels.
Theophylline: This methylxanthine drug is used for acute relief in respiratory diseases such as COPD and asthma. This drug is metabolised by cytochrome P450 3A4,[435],[436] and has a narrow therapeutic range.[437],[438] Human evidence shows constituents of liquorice induce the activity of this enzyme,[439] with animal evidence showing the whole herb to exert a similar effect,[440] which theoretically may change the drug’s therapeutic effect.[441],[442] Use cautiously in patients on this medication and monitor for any adverse effects.
Thyroid dysfunction/disease: Use with caution and monitor patient for symptoms of thyroid dysfunction. Monitor thyroid hormone levels if altered thyroid function is suspected.There is some evidence that withania can stimulate thyroid hormone synthesis or secretion. Theoretically, withania might exacerbate hyperthyroidism as it might increase thyroid hormone levels.[443]
Tyrosine is a precursor to thyroid hormone which may increase thyroid hormone levels and may have an additive effect when taken alongside thyroid medication.[444],[445]
Tipranavir: This HIV antiretroviral protease inhibitor is metabolised by P-glycoprotein and cytochrome P450 3A4, and has a narrow therapeutic range.[446],[447] Rhodiola has the potential to affect the clearance of drugs that are transported via P-glycoprotein;[448],[449] additionally, human evidence shows constituents of liquorice induce the activity of CYP3A4,[450] with animal evidence showing the whole herb to exert a similar effect,[451] which theoretically may change the drug’s therapeutic effect.[452],[453] Use cautiously in patients on this medication and monitor for symptom changes.
Valproate (sodium valproate): This anti-epileptic, anticonvulsant and anti-seizure drug is metabolised by cytochrome P450 3A4,[454],[455] and has a narrow therapeutic range.[456] Human evidence shows constituents of liquorice induce the activity of this enzyme,[457] with animal evidence showing the whole herb to exert a similar effect,[458] which theoretically may change the drug’s therapeutic effect.[459],[460] Use cautiously in patients on this medication and monitor for any adverse effects.
Pregnancy and Breastfeeding
Pregnancy: Contraindicated.Withania is generally not for use in pregnancy except under the supervision of a qualified health practitioner.
There are references to Withania as an ‘abortifacient’ and a ‘pregnancy tonic.’ The strength or accuracy of this information is difficult to assess given the lack of detail. It may be that low doses pose little danger; however clinicians should discuss the strength and limitations of the evidence when counselling about its use in pregnancy.
Western texts urge caution in pregnancy due to a reputed abortifacient activity and antifertility effects notes in early animal studies, despite there being no evidence of fetal damage. Note that withania is used to support pregnancy and lactation in the ayurvedic tradition.[461],[462],[463]
Liquorice is unlikely to cause adverse effects if used for preconception and in the early weeks of pregnancy. However, a monthly pregnancy test is recommended, and liquorice should be discontinued once pregnancy is confirmed. Two studies have shown that high glycyrrhizin intake during pregnancy significantly increased the likelihood of early delivery, although did not affect birth weight or maternal blood pressure. Additionally, children who were exposed to high glycyrrhizin exposure prenatally (≥500 mg/wk) experienced changes to cognitive and psychiatric development.[464],[465] Therefore, it is recommended to avoid the use of liquorice during pregnancy.
Breastfeeding: Appropriate for use.[466],[467],[468]No risks found in humans with the use of tyrosine[469] or liquorice[470],[471] during lactation, although research is limited or unavailable.
Children: No available information
MGXATS
