Simplified Stress Management Protocol

A personalized protocol with proven interventions and evidenced-based supplements streamlines stress-management, ensures compliance and boosts patient outcomes.

Stress may be accepted as troublesome fact of modern life. But pervasive tension and anxiety are dangerous, even deadly. In the short term, stress disrupts mood and cognitive function, drives inflammation and dysregulates immune response. Over time, chronic stress heightens the risk of neurodegenerative disorders, diabetes, cardiovascular disease, cancer and other serious diseases, and stress-related conditions have been linked with higher all-cause mortality.^{1, 2, 3, 4, 5}

But stress is a complex situation, and a scattered or unduly complicated regimen with too many interventions can overburden an already-fragile nervous system and overwhelm patients, decreasing compliance, fueling frustration and increasing stress. Meanwhile, myriad bidirectional relationships exist between stress, sleep, diet and other factors, further confounding treatment protocols.

To simplify matters, begin by identifying influences or behaviors to minimize or eliminate and those to encourage. A streamlined, strategic approach will support your patients’ consistency and improve results. Personalized protocols should account for individual considerations: a patient’s experience or willingness, as well as financial and other resources should inform any stress-management plan. Here’s what the research shows:

Stress foes—what to minimize or eliminate.

• Sleep deprivation. Chronic lack of sleep is linked with a markedly higher incidence of anxiety and mental distress, and people who suffer from insomnia are significantly more vulnerable to stress. Insufficient sleep raises cortisol levels and intensifies reactivity in the amygdala and anterior insula, brain regions involved in emotional processing and experience; the amygdala is especially associated with fear and anxiety. Sleep deprivation also impairs attention span, problem-solving skills and emotional regulation, heightening sensitivity to stress and anxiety triggers. Research shows a bidirectional relationship between sleep issues and anxiety: lack of sleep exacerbates anxiety and stress, which leads to insomnia, sleep deprivation and an ongoing negative cycle.^{6, 7, 8, 9, 10}
• Stimulant overuse. Excess caffeine amplifies anxiety, disrupts sleep and dampens stress resilience. High caffeine intake is linked with an increased risk of anxiety and research shows it aggravates symptoms of anxiety, panic disorders and insomnia. Too much screen time and media exposure likewise overstimulate the brain and studies have demonstrated a correlation between prolonged screen time and greater levels of stress and anxiety, as well as depression. One study found a relationship between frequent smartphone use, elevated anxiety and lower quality of sleep. Blue light emitted from devices is also known to interfere with sleep, further exacerbating stress and diminishing emotional regulation.^{11, 12, 13, 14, 15}
• Poor eating habits. The typical Western diet high in processed or fried foods, refined grains and sugary foods is associated with more psychological symptoms, including increased stress and anxiety. Additionally, processed foods, excessive sugar and trans fats fuel neuroinflammation, shown to trigger psychiatric disorders like depression and anxiety in otherwise healthy people. Poor diet is known to disrupt the microbiome, impairing mood and contributing to stress and anxiety. Eating habits also impact sleep: low-fiber, high-sugar diets are linked with sleep disturbances, as are deficiencies in key vitamins and minerals.^{16, 17, 18, 19}
• Unresolved trauma. Emotional trauma, stress and anxiety are closely related, and unresolved trauma significantly heightens the risk of developing anxiety disorders and other conditions. Traumatic experiences, especially during childhood, produce enduring negative effects on brain structure and function, impacting emotional processing and stress regulation and increasing a patient’s vulnerability to anxiety as well as depression, substance abuses and impairment in other life areas. In the absence of treatment, lingering trauma can drive intrusive thoughts, flashbacks and nightmares, interfere with sleep, disrupt emotional balance and intensify anxiety.^{20, 21, 22, 23, 24}

Stress-management allies—what to encourage:

• Optimize sleep. Deep, restorative sleep is known to modulate cortisol, restore circadian rhythms, boost resilience to stress and lessen anxiety. In addition to diet and lifestyle modifications, sleep hygiene practices like maintaining a consistent sleep schedule, limiting electronics before bed and creating an environment conducive to sleep, are simple and effective ways to promote restful sleep. Exposure to sunlight, especially in the morning, restores circadian rhythm and improve sleep, mood and general well-being. Several studies report daytime exposure to white light increased evening fatigue and sleep quality, decreased sleep-onset latency and enhanced slow-wave sleep.^{25, 26, 27, 28, 29, 30}
• Prioritize exercise. Regular physical activity has been shown to modulate cortisol, improve sleep and mood, and ease stress and anxiety. In one study, six 20-minute sessions of aerobic exercise significantly reduced anxiety sensitivity, and bouts of acute exercise can minimize anxiety, even in patients with panic disorder. Additionally, physical activity benefits sleep quality and duration—essential for addressing stress. Besides aerobic exercise, slow, meditative movement practices such as yoga, tai chi and qi gong influence the sympathetic nervous system and effectively alleviate stress and anxiety.^{31, 32, 33, 34, 35, 36, 37, 38}
• Regulate emotions. Mindfulness practices like Mindfulness-Based Stress Reduction (MBSR) are valuable allies for improving emotional regulation and managing stress. In research MBSR decreased amygdala activity, increased activity in brain regions involved in attentional deployment, and lessened emotional reactivity and negative emotions. One clinical trial found a mindfulness-based stress reduction program was as effective as pharmaceutical treatment for patients with anxiety disorders. Other studies show MBSR not only decreases stress, anxiety and depression, but also promotes empathy and self-compassion.^{39, 40, 41, 42, 43}
• Retrain the brain. Cognitive Behavioral Therapy (CBT) is a powerful tool for helping patients reframe negative thought patterns that drive stress and anxiety, learn adaptive behaviors in response to triggers and build self-regulation. A number of studies point to CBT as a promising intervention for alleviating stress and different forms of anxiety. CBT is also widely used for treating various types of trauma, including post-traumatic stress disorder (PTSD), with research showing CBT effectively helps manage stress, anxiety, disrupted sleep and other trauma-related symptoms.^{44, 45, 46, 47}
• Correct nutritional deficiencies. A range of essential vitamins, minerals and nutrients are involved in regulating mood and stress hormones, and deficiencies interfere with neurotransmitter production, exacerbate sleep disturbances and heighten stress and anxiety. Correcting nutrient deficiencies is vital in the management of stress and behavioral health disorders. Foundational supplementation designed to address micronutrient deficiencies can support sleep and mood, improve resilience to stress and enhance the effectiveness of other interventions.^{48, 49, 50, 51, 52}

Science-backed supplements to tame stress.

In addition to filling in nutritional gaps, evidence-based supplements shown to influence neurotransmitters, dampen cortisol, modulate neuroinflammation and improve the microbiome offer fast symptom relief, especially during high-stress periods. Five essentials that form the framework of a comprehensive stress-management protocol.

1. GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the brain, and low levels or impaired functioning are associated with higher incidence of stress, anxiety disorders and sleep disturbances. Enhancing GABA levels through supplementation may calm the nervous system, act as a natural relaxant and ease stress. It’s thought to work in part by modulating neuroinflammation and imbalances in neurotransmitter systems, linked with anxiety disorders. Other research suggests GABA mitigates stress and anxiety by influencing the gut-brain axis, regulating the microbiome, and possibly preventing nitric oxide (NO) reduction caused by stress. It appears to act rapidly: one study found GABA significantly increased alpha waves and decreased beta waves within 1 hour of administration. GABA supplementation has also been shown to improve sleep, support immunity under conditions of stress, and alleviate depression.^{53, 54, 55, 56, 57, 58, 59}
2. L-theanine, found primarily in green tea, has proven anxiolytic and stress-reducing properties. Like GABA, it works rapidly: in one study, L-theanine increased alpha brain wave activity 40 minutes after ingestion and decreased cortisol in as little as 20 minutes. L-theanine also influences neurotransmitter levels and is especially noted for its ability to enhance GABAergic activity and promote calming. The relaxation effects of L-theanine have been validated by numerous studies showing L-theanine reduced stress and anxiety and improved stress-related symptoms. Other research points to its significant therapeutic benefits for mood, depression, emotional balance, cognitive function and sleep, as well as its neuroprotective properties. Suntheanine, a concentrated and patented brand, is considered a higher purity, more bioavailable form of L-theanine.^{60, 61, 62, 63, 64, 65, 66, 67, 68}
3. Vitamin B6 (pyridoxine) plays a crucial role in the production of neurotransmitters involved in regulating mood, anxiety and stress responses, with studies confirming its significant and selective modulatory impact on serotonin and GABA production. Low intake of vitamin B6 are linked with increased incidence of anxiety, depression and mood disorders, and supplementation may relieve stress and anxiety and boost mood. In one study of healthy young adults, vitamin B6 supplementation significantly reduced feelings of stress, anxiety and depression, and other research highlights its ability to enhance cognitive function, treat mood disorders and improve well-being. Vitamin B6 appears to be especially effective when combined with magnesium, minimizing the stress response and promoting a more relaxed state.^{69, 70, 71, 72, 73, 74, 75}
4. 5-HTP (L-5-hydroxytryptophan) acts as the precursor to serotonin and melatonin, and its synthesis represents the limiting step in serotonin and melatonin biosynthesis. 5-HTP supplementation may increase melatonin and serotonin levels, and both human and animal studies demonstrate its anxiolytic-like activities. Brain serotonergic pathways are involved in the pathogenesis of anxiety disorders, particularly agoraphobia and panic disorders. Research on patients suffering from anxiety have found 5-HTP significantly reduced anxiety compared to placebo. 5-HTP also appears to mitigate stress by influencing gut microbiota, and studies confirm its beneficial effects on mood, sleep and depression.^{76, 77, 78, 79, 80, 81, 82, 83}
5. Ashwagandha, used for centuries in traditional Ayurvedic medicine, is a known adaptogen, regulating various physiological processes to decrease stress and promote resilience. It works in part by modulating cortisol, and research demonstrate its effectiveness in lowering serum cortisol levels, especially in people with current stress or anxiety. A number of clinical trials highlight ashwagandha’s ability to manage stress and significantly reduce anxiety in both healthy patients and those with anxiety disorder. Ashwagandha extract also has positive impacts on several aspects of sleep, including sleep quality, sleep efficiency, total sleep time and sleep latency. In other studies, ashwagandha improved memory, concentration, mental clarity, focus, energy levels, psychological well-being and quality of life, Sensoril, a proprietary extract with a wider range of bioactive compounds, has been extensively researched, with studies finding significant improvements in stress and anxiety scores, as well as a reduction of cortisol and C-reactive protein (CRP) and other stress biomarkers.^{84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95}

Related: 

References:

1. Cohen S et al. Psychological stress and disease. JAMA. 2007 Oct 10;298(14):1685-7.
2. Mariotti A. The effects of chronic stress on health: new insights into the molecular mechanisms of brain-body communication. Future Sci OA. 2015 Nov 1;1(3):FSO23.
3. Liu YZ et al. Inflammation: The Common Pathway of Stress-Related Diseases. Front Hum Neurosci. 2017 Jun 20;11:316.
4. Rohleder N. Stress and inflammation – The need to address the gap in the transition between acute and chronic stress effects. Psychoneuroendocrinology. 2019 Jul;105:164-171.
5. Tian F et al. Association of stress-related disorders with subsequent risk of all-cause and cause-specific mortality: A population-based and sibling-controlled cohort study. Lancet Reg Health Eur. 2022 May 28;18:100402.
6. Blackwelder A et al. Effect of Inadequate Sleep on Frequent Mental Distress. Prev Chronic Dis 2021;18:200573.
7. Kalmbach DA et al. Insomnia symptoms and short sleep predict anxiety and worry in response to stress exposure: a prospective cohort study of medical interns. Sleep Med. 2019 Mar;55:40-47.
8. Goldstein AN et al. Tired and apprehensive: anxiety amplifies the impact of sleep loss on aversive brain anticipation. J Neurosci. 2013 Jun 26;33(26):10607-15.
9. Palmer CA et al. Sleep loss and emotion: A systematic review and meta-analysis of over 50 years of experimental research. Psychol Bull. 2024 Apr;150(4):440-463.
10. Richards A et al. Sleep disturbance in PTSD and other anxiety-related disorders: an updated review of clinical features, physiological characteristics, and psychological and neurobiological mechanisms. Neuropsychopharmacology. 2020 Jan;45(1):55-73.
11. Liu C et al. Caffeine intake and anxiety: a meta-analysis. Front Psychol. 2024 Feb 1;15:1270246.
12. Addicott MA. Caffeine Use Disorder: A Review of the Evidence and Future Implications. Curr Addict Rep. 2014 Sep;1(3):186-192.
13. Vilarim MM et al. Caffeine challenge test and panic disorder: A systematic literature review. Expert Rev Neurother. 2011;11:1185–1195.
14. Khan A et al. Excessive Smartphone Use is Associated with Depression, Anxiety, Stress, and Sleep Quality of Australian Adults. J Med Syst. 2023 Oct 20;47(1):109.
15. Francisquini MCJ et al. Associations of screen time with symptoms of stress, anxiety, and depression in adolescents. Rev Paul Pediatr. 2024 Sep 9;43:e2023250.
16. Jacka FN et al. Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry.  2010;167:305–311
17. Kip E, Parr-Brownlie LC. Healthy lifestyles and wellbeing reduce neuroinflammation and prevent neurodegenerative and psychiatric disorders. Front Neurosci. 2023 Feb 15;17:1092537.
18. Chrzastek Z et al. Dietary factors, risk of developing depression, and severity of its symptoms in older adults-A narrative review of current knowledge. Nutrition. 2023 Feb;106:111892.
19. Bear TLK et al. The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety. Adv Nutr. 2020 Jul 1;11(4):890-907.
20. Kascakova N et al. The Unholy Trinity: Childhood Trauma, Adulthood Anxiety, and Long-Term Pain. Int J Environ Res Public Health. 2020 Jan 8;17(2):414.
21. Kisely S. Child maltreatment and mental health problems in adulthood: Birth cohort study. Br. J. Psychiatry. 2018;213:698–703.
22. Fernandes V, Osório FL. Are there associations between early emotional trauma and anxiety disorders? Evidence from a systematic literature review and meta-analysis. Eur. Psychiatry. 2015;30:756–764.
23. Norman RE. The long-term health consequences of child physical abuse, emotional abuse, and neglect: A systematic review and meta-analysis. PLoS Med. 2012;9:e1001349.
24. Center for Substance Abuse Treatment (US). Trauma-Informed Care in Behavioral Health Services. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2014. (Treatment Improvement Protocol (TIP) Series, No. 57.) Chapter 3, Understanding the Impact of Trauma.
25. Desai D et al. Exploring the Role of Circadian Rhythms in Sleep and Recovery: A Review Article. Cureus. 2024 Jun 3;16(6):e61568.
26. Blume C et al. Effects of light on human circadian rhythms, sleep and mood. Somnologie (Berl). 2019 Sep;23(3):147-156.
27. Viola AU et al. Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality. Scand J Work Environ Health. 2008;34(4):297–306.
28. Boubekri M, Cheung IN, Reid KJ, et al. Impact of windows and daylight exposure on overall health and sleep quality of office workers: a case-control pilot study. J Clin Sleep Med. 2014;10:603–611
29. Figueiro MG et al. The impact of daytime light exposures on sleep and mood in office workers. Sleep Health. 2017;3:204–215.
30. Wams EJ et al. Linking Light Exposure and Subsequent Sleep: A Field Polysomnography Study in Humans. Sleep. 2017 Dec 1;40(12):zsx165.
31. De Nys L et al. The effects of physical activity on cortisol and sleep: A systematic review and meta-analysis. Psychoneuroendocrinology. 2022 Sep;143:105843.
32. Anderson E, Shivakumar G. Effects of exercise and physical activity on anxiety. Front Psychiatry. 2013 Apr 23;4:27.
33. Smits JA et al. Reducing anxiety sensitivity with exercise. Depress Anxiety. 2008;25(8):689-99.
34. Broman-Fulks JJ, Storey KM. Evaluation of a brief aerobic exercise intervention for high anxiety sensitivity. Anxiety Stress Coping. 2008 Apr;21(2):117-28.
35. Alnawwar MA et al. The Effect of Physical Activity on Sleep Quality and Sleep Disorder: A Systematic Review. Cureus. 2023 Aug 16;15(8):e43595.
36. Xie Y et al. Effects of Exercise on Sleep Quality and Insomnia in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Psychiatry. 2021 Jun 7;12:664499.
37. Zou L et al. Effects of Mind⁻Body Exercises (Tai Chi/Yoga) on Heart Rate Variability Parameters and Perceived Stress: A Systematic Review with Meta-Analysis of Randomized Controlled Trials. J. Clin. Med. 2018;7:404
38. Chen KW et al. Meditative therapies for reducing anxiety: a systematic review and meta-analysis of randomized controlled trials. Depress Anxiety. 2012 Jul;29(7):545-62.
39. Goldin PR, Gross JJ. Effects of mindfulness-based stress reduction (MBSR) on emotion regulation in social anxiety disorder. Emotion. 2010 Feb;10(1):83-91.
40. Ramel W et al. The effects of mindfulness meditation on cognitive processes and affect in patients with past depression. Cognitive Therapy and Research. 2004;28:433–455
41. Chiesa A, Serretti A. Mindfulness-based stress reduction for stress management in healthy people: a review and meta-analysis. J Altern Complement Med. 2009 May;15(5):593-600.
42. Hoge EA et al. Mindfulness-Based Stress Reduction vs Escitalopram for the Treatment of Adults With Anxiety Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Jan 1;80(1):13-21.
43. Evans S et al. Mindfulness-based cognitive therapy for generalized anxiety disorder. J Anxiety Disord. 2008 May;22(4):716-21.
44. Pollio E, Deblinger E. Trauma-focused cognitive behavioural therapy for young children: clinical considerations. Eur J Psychotraumatol. 2018 Mar 15;8(Suppl 7):1433929.
45. Curtiss JE et al. Cognitive-Behavioral Treatments for Anxiety and Stress-Related Disorders. Focus (Am Psychiatr Publ). 2021 Jun;19(2):184-189.
46. Murray H et al. Ten misconceptions about trauma-focused CBT for PTSD. Cogn Behav Therap. 2022 Jul 22;15:s1754470x22000307.
47. Feng G et al. The Clinical Effectiveness of Cognitive Behavioral Therapy for Patients with Insomnia and Depression: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2020 Jul 15;2020:8071821.
48. Bremner JD et al. Diet, Stress and Mental Health. Nutrients. 2020 Aug 13;12(8):2428.
49. Ikonte CJ et al. Micronutrient Inadequacy in Short Sleep: Analysis of the NHANES 2005-2016. Nutrients. 2019 Oct 1;11(10):2335.
50. Kris-Etherton PM et al. Nutrition and behavioral health disorders: depression and anxiety. Nutr Rev. 2021 Feb 11;79(3):247-260.
51. Grosso G et al. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One. 2014;9:e96905.
52. Sarris J et al. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015;2:271–274
53. Hepsomali P et al. Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Front Neurosci. 2020 Sep 17;14:923.
54. Nemeroff CB. The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull. 2003;37:133–146.
55. Abdou AM et al. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-8.
56. Xu J et al. Long-term GABA supplementation mitigates anxiety by modulating complement and neuroinflammatory pathways. NPJ Sci Food. 2025 Apr 24;9(1):60.
57. Liwinski T et al. Exploring the Therapeutic Potential of Gamma-Aminobutyric Acid in Stress and Depressive Disorders through the Gut-Brain Axis. Biomedicines. 2023 Nov 24;11(12):3128.
58. Braga JD et al. Gamma-aminobutyric acid as a potential postbiotic mediator in the gut-brain axis. NPJ Sci Food. 2024 Apr 2;8(1):16.
59. He Y et al. Intervention mechanism of repeated oral GABA administration on anxiety-like behaviors induced by emotional stress in rats. Psychiatry Res. 2019 Jan;271:649-657.
60. Evans M et al. A Randomized, Triple-Blind, Placebo-Controlled, Crossover Study to Investigate the Efficacy of a Single Dose of AlphaWave® L-Theanine on Stress in a Healthy Adult Population. Neurol Ther. 2021 Dec;10(2):1061-1078
61. Dashwood R, Visioli F. l-theanine: From tea leaf to trending supplement – does the science match the hype for brain health and relaxation? Nutr Res. 2025 Feb;134:39-48. .
62. Nathan PJ et al. The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2):21-30.
63. Lu K et al. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol. 2004;19(7):457–65.
64. Everett JM et al. Theanine consumption, stress and anxiety in human clinical trials: A systematic review. J Nutr Intermed Metab. 2016;4:41-42.
65. Williams JL et al. The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review. Plant Foods Hum Nutr. 2020 Mar;75(1):12-23.
66. Hidese S et al. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019 Oct 3;11(10):2362.
67. Nobre AC et al. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8.
68. Li MY et al. L-Theanine: A Unique Functional Amino Acid in Tea (Camellia sinensis L.) With Multiple Health Benefits and Food Applications. Front Nutr. 2022 Apr 4;9:853846.
69. Durrani D et al. Vitamin B6: A new approach to lowering anxiety, and depression? Ann Med Surg (Lond). 2022 Sep 15;82:104663.
70. McCarty MF. High-dose pyridoxine as an ‘anti-stress’ strategy. Med. Hypotheses. 2000 May;54(5):803–807.
71. Odai T et al. Depressive Symptoms in Middle-Aged and Elderly Women Are Associated with a Low Intake of Vitamin B6: A Cross-Sectional Study. Nutrients. 2020 Nov 9;12(11):3437.
72. Ekinci GN, Sanlier N. The relationship between nutrition and depression in the life process: A mini-review. Exp Gerontol. 2023 Feb;172:112072.
73. Mahdavifar B et al. Dietary intake of B vitamins and their association with depression, anxiety, and stress symptoms: A cross-sectional, population-based survey. J Affect Disord. 2021 Jun 1;288:92-98.
74. Field DT et al. High-dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression. Hum Psychopharmacol. 2022 Nov;37(6):e2852.
75. Pouteau E et al. Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PLoS One. 2018 Dec 18;13(12):e0208454.
76. Maffei ME. 5-hydroxytryptophan (5-HTP): natural occurrence, analysis, biosynthesis, biotechnology, physiology and toxicology. Int J Mol Sci. 2020;22(1):181. Published 2020 Dec 26.
77. Javelle F et al. Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis. Nutr Rev. 2020;78(1):77-88.
78. Carnevale G et al. Anxiolytic-like effect of griffonia simplicifolia baill. Seed extract in rats. Phytomedicine. 2011;18:848–851.
79. Schruers K et al. Acute l-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Psychiatry Res. 2002;113:237–243.
80. Maron E et al. The effect of 5-hydroxytryptophan on chotecystokinin-4-induced panic attacks in healthy volunteers. J Psychopharmacol. 2004;18:194–199.
81. Sutanto C et al. The impact of 5-hydroxytryptophan supplementation on sleep quality of older adults in Singapore: a randomized controlled trial. Curr Dev Nutr. 2021;5(Suppl 2):372. Published 2021 Jun 7.
82. Shaw K et al. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.
83. Meloni M et al. Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease. Sleep Breath. 2022;26(3):1023-1031.
84. Auddy B et al. A standardized Withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: A double-blind, randomized, placebo-controlled study. J Am Nutraceutical Assoc. 2008;11:50–6.
85. Chandrasekhar K et al. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012 Jul-Sep; 34(3): 255–262.
86. Salve J et al. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus. 2019 Dec 25;11(12):e6466.
87. Gopukumar K et al. Efficacy and safety of ashwagandha root extract on cognitive functions in healthy, stressed adults: a randomized, double-blind, placebo-controlled study. Evid Based Complement Alternat Med. 2021;2021:8254344.
88. Lopresti AL et al. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: a randomized, double-blind, placebo-controlled study. Med. 2019;98:e17186.
89. Pingali U et al. Effect of Withania somnifera extract on mental stress induced changes in hemodynamic properties and arterial wave reflections in healthy subjects. Curr Top Nutraceutical Res. 2013;11:151–158.
90. Mishra DN, Kumar M. Shoden promotes Relief from stress and anxiety: A randomized, double-blind, placebo-controlled study on healthy subjects with high stress levels. Heliyon. 2024 Aug 29;10(17):e36885.
91. Fuladi S et al. Assessment of the Efficacy of Withania somnifera Root Extract in Patients with Generalized Anxiety Disorder: A Randomized Double-blind Placebo- Controlled Trial. Curr Rev Clin Exp Pharmacol. 2021;16(2):191-196.
92. Pandit S et al. Effects of Withania somnifera Extract in Chronically Stressed Adults: A Randomized Controlled Trial. Nutrients. 2024 Apr 26;16(9):1293.
93. Majeed M et al. A standardized Ashwagandha root extract alleviates stress, anxiety, and improves quality of life in healthy adults by modulating stress hormones: Results from a randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2023 Oct 13;102(41):e35521.
94. Smith SJ et al.  Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2023 Nov;37(11):1091-1104.
95. Fatima K et al. Safety and efficacy of Withania somnifera for anxiety and insomnia: Systematic review and meta-analysis. Hum Psychopharmacol. 2024 Nov;39(6):e2911.