By Gene Bruno, MS, MHS, RH(AHG), Vice President of Scientific & Regulatory Affairs, NutraScience Labs09.09.21
According to the American Psychological Association, a bitter election season, political unrest and violence, a shaky economy, and COVID-19 related issues have affected the stress levels of Americans.1 In fact, 84% of adults reported feeling at least one emotion associated with prolonged stress in the prior two weeks. The most common were feelings of anxiety (47%), sadness (44%), and anger (39%). Furthermore, 2 in 3 adults (67%) said the number of issues America is facing is overwhelming to them.
Stress Supplement Sales Trends
So how do you think these increased levels of stress impact sales of stress supplements? If your answer is you think it caused an increase in sales, you are correct. Sales for anxiety/stress relief dietary supplements in 2020 grew 79% from 2018.2 Furthermore, trends seem to indicate that sales of these products won’t be slowing down anytime soon. According to Goldstein Market Intelligence, global sales of stress management supplements are expected to grow at a CAGR of 2.3% during the 2017-2030 period.3
With stress-relief products a starring dietary supplement category, let’s consider the types of nutraceuticals that are directly applicable to stress formulations.
B-Complex Vitamins
The B-complex vitamins are intimately involved in the function of the nervous system, and so can play a role in helping to counter some of the negative effects of stress.4 In fact, the ability of humans to respond to stress can be influenced by nutritional status—including the status of key B vitamins.5
In one study, vitamin B1 (thiamine) and vitamin B6 (pyridoxine) together were found to be especially necessary for workers whose activity is associated with nervous-emotional stress.6 Similar results were seen in a previous study.7
Research on individual B vitamins has also revealed important roles where stress and the nervous system are concerned. This includes vitamin B1 which protected against functional exhaustion,8 pantothenic acid (B5) which supports production of adrenal hormones associated with stress,9 and similar results with other B vitamins. A 12-week study conducted on 60 people found that those consuming one or two forms of vitamin B complex supplements were found to experience fewer work-related symptoms of stress, anger, and fatigue compared to the placebo group.10
Phosphatidylserine
Research has demonstrated that phosphatidylserine (PS) was able to blunt the release of cortisol—the “stress hormone”—in response to exercise stress.11 In some cases, PS supplementation also resulted in improved mood.12-13 A subsequent randomized, double-blind, placebo-controlled study found that, compared to placebo, supplementation with 300 mg PS/day was associated with feeling less stressed (p<0.001) and having a better mood with regard to feeling clear-headed (p<0.02), composed (p<0.03), and confident (p<0.02).14
L-Theanine
The amino acid L-theanine has been shown to increase both serotonin and dopamine production,15 and possibly gamma amino butyric acid (GABA) as well.16
Evidence from human electroencephalograph (EEG) studies show that it also significantly increases brain activity in the alpha frequency band, which indicates that it relaxes the mind without inducing drowsiness. Other research indicates that L-theanine has a significant effect on improving mental alertness while promoting relaxation.17 Additional studies have shown that supplementation with L-theanine resulted in a reduction in some physiological indicators of stress within 15 minutes,18 suppressed the initial stress response of students,19 and significantly reduced anxiety and reduced the blood-pressure increase in high-stress-response adults.20
Apocynum Venetum
Apocynum venetum is an herbal remedy with a long history of use in Traditional Chinese Medicine for soothing the nerves, and for other purposes.21 In a double-blind, randomized trial, individuals with mild depression and symptoms of anxiety were treated with Apocynum venetum leaf extract or placebo at different times over 8 weeks.22 Researchers found that after 8 weeks of treatment, subjects showed a significant decrease in depression scores, and had significant improvements in anxiety.
GABA
GABA is the primary neurotransmitter in the central nervous system for exerting anti-anxiety effects.23 A study investigated the effect of GABA on relaxation and stress in humans, showing that it significantly increased relaxing alpha waves.24 Another study found that GABA supplementation reduced psychological stress induced by an arithmetic task.25 Other research examined the effectiveness of Apocynum venetum and GABA used together, showing that the combination was able to reduce markers of cognitive-induced mental stress.26
Ashwagandha
Ashwagandha (Withania somnifera) is an adaptogenic herb historically used in Asia for treating stress-related health conditions. In one study, an ashwagandha extract was used in chronically stressed people.27 Results indicated subjects experienced a reduction in anxiety as well as serum cortisol (a stress hormone). Overall, the study showed that ashwagandha significantly reduced experiential and biochemical indicators of stress without adverse effects. Other effective adaptogenic herbs include ginseng and Rhodiola.
Panax Ginseng
Panax ginseng root, or ginseng for short, is a traditional Chinese herb which has been used for thousands of years in various aspects of healthcare. It is also one of the most widely researched herbs in modern science with over 5,000 published studies.
Ginseng helps stabilize physiological processes and promote homeostasis, especially in the case of stress and fatigue. This property was seen in two human clinical studies examining the effects of ginseng on mental performance.28-29 The results demonstrated that ginseng root extract improved speed of mental performance within 60 minutes, enhanced performance of mental arithmetic within 60 minutes, reduced feelings of mental fatigue within 60 minutes, quickly reduced feelings of mental fatigue during sustained mental activity, and quickly improved some measures of mental performance.
Rhodiola Rosea Root Extract
Rhodiola rosea root, another adaptogen, has been used for centuries in the traditional systems of healthcare throughout Russia, Scandinavia, and other countries where it was used to increase physical endurance, work productivity, and longevity, as well as to treat fatigue, mood, and promote a healthy nervous system.30
Currently, there are over 500 studies on Rhodiola demonstrating the value of this plant. Human clinical research shows that supplementation with Rhodiola can improve capacity for mental work during stress, support healthy cognitive function during stress, and reduce fatigue during stress.31-33
Conclusion
There are many other nutraceuticals with applications for stress but this overview provides some science-based nutraceutical options for addressing some of the most common issues associated with stress.
About the Author: Gene Bruno, MS, MHS, RH(AHG) possesses 42 years of dietary supplement industry experience. With a Master’s degree in nutrition and a second Master’s degree in herbal medicine, he has a proven track record of formulating innovative, evidence-based dietary supplements. Bruno currently serves as both the Vice President of Scientific and Regulatory Affairs at NutraScience Labs and Professor of Nutraceutical Science at Huntington University of Health Sciences where he’s taught doctors, nurses, and pharmacists about integrative healthcare. He also writes extensively on nutrition, health, and nutraceuticals and has formulated hundreds of evidence-based dietary supplements, including fitness, health, and wellness products. For more information: www.nutrasciencelabs.com.
References
1. APA: U.S. Adults Report Highest Stress Level Since Early Days of the COVID-19 Pandemic. American Psychological Association. February 2, 2021. Retrieved July 22, 2021 from https://www.apa.org/news/press/releases/2021/02/adults-stress-pandemic
2. Francis E. COVID-19 Stress Drives Anxiety-Reducing Supplement Sales Up 79% In US Since 2018. HBW Insight. 30 Apr 2021. Retrieved July 22, 2021 from https://hbw.pharmaintelligence.informa.com/RS151287/COVID19-Stress-Drives-AnxietyReducing-Supplement-Sales-Up-79-In-US-Since-2018
3. Global Stress Management/Relief Supplements Market Report- Trends, Share, Key Players, Manufacturer’s List, Trade Data, Industry Analysis, By Supplement (Tryptophan, Zinc, Magnesium, Vitamin B, Iron Supplement), By Nature(Herbal & Chemical Based), By Distribution Channel With COVID-19 Impact | Forecast Period 2017-2030. Goldstein Market Intelligence. May 24, 2021. 887 pgs.
4. Whitney E, Rolfes S. Understanding Nutrition, Ninth Edition, Belmont, CA: Wadsworth/Thomson Learning; 2002.
5. Sauberlich HE. Implications of nutritional status on human biochemistry, physiology, and health. Clin Biochem 1984; 17(2):132-42.
6. Bondarev GI, Martinchik AN, Khotimchenko SA, et al. [Correlation of the actual vitamin B1, B2 and B6 consumption with the biochemical indices of their body allowance] Korreliativnaia vzaimosviaz’ fakticheskogo potrebleniia vitaminov B1, B2 i B6 s biokhimicheskimi pokazateliami obespechennosti imi organizma. Vopr Pitan 1986; (2):34-7.
7. Bogdanov NG, Bondarev GI, Piatnitskaia IN, et al. [Vitamin status of diamond cutters] Vitaminnyi status rabochikn, zaniatykh promyshlennoi obrabotkoi almazov. Vopr Pitan 1984; (2):28-31.
8. Vinogradov VV, Tarasov IuA, Tishin VS, et al. [Thiamine prevention of the corticosteroid reaction after surgery] Optimizatsiia tiaminom korticosteroidnoi reaktsii pri khirurgicheskikh vmeshatel’stvakh. Probl Endokrinol 1981; 27(3):11-6.
9. Kutsky R, Handbook of Vitamins and Hormones. New York: Van Nostrand Reinhold Company; 1973:208.
10. Stough C, Scholey A, Lloyd J, et al. The effect of 90 day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. 2011 Oct;26(7):470-6.
11. Fahey TD, Pearl MS. The hormonal and perceptive effects of phosphatidylserine administration during two weeks of resistive exercise-induced overtraining. Biol Sport. 1998;15:135-44.
12. Monteleone P, Maj M, Beinat L, Natale M, Kemali D. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol. 1992;42(4):385-8.
13. Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990 Sep;52(3):243-8.
14. Benton D, Donohoe RT, Sillance B, Nabb S. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci. 2001;4(3):169-78.
15. L-Theanine monograph. Alternative Medicine Review 2005;10(2):136-8.
16. Lu K, Gray MA, Oliver C, et al. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol Clin Exp 2004;19:457–65.
17. Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr 2008;17 Suppl 1:167-8.
18. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol 2007;74(1):39-45.
19. Unno K, Tanida N, Ishii N, et al. Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary α-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav. 2013 Oct;111:128-35.
20. Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012 Oct 29;31:28.
21. Xie W, Zhang X, Wang T, Hu J. Botany, traditional uses, phytochemistry and pharmacology of Apocynum venetum L. (Luobuma): A review. J Ethnopharmacol. 2012 May 7;141(1):1-8.
22. Venetron® brochure, Tokiwa. Summarized in Maypro document “Venetron Clinical Evidence.” Topic: What was the effect of a daily dose of 50 mg of Venetron® in individuals with mild depression over 8 weeks?
23. Kalant H, Roschlau WHE, Eds. Principles of Med. Pharmacology. New York, NY: Oxford Univ Press, 1998.
24. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-8.
25. Nakamura H, Takishima T, Kometani T, Yokogoshi H. Psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA) in humans: assessment of stress using heart rate variability and salivary chromogranin A. Int J Food Sci Nutr. 2009;60 Suppl 5:106-13.
26. Yoto A, Ishihara S, Li-Yang J, Butterweck V, Yokogoshi H. The Stress Reducing Effect of γ-Aminobutyric Acid and Apocynum venetum Leaf Extract on Changes in Concentration of Salivary Chromogranin A. Japanese Journal of Physiological Anthropology. 2009 14(3): 55-59.
27. Auddy B, Hazra J, Mitra A, Abedon B, Ghosal S. A Standardized Withania Somnifera Extract Significantly Reduces Stress-Related Parameters in Chronically Stressed Humans: A Double-Blind, Randomized, Placebo-Controlled Study. JANA. 2008;11(1):2008:50-56.
28. 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 Jul;19(4):357-65.
29. 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 Nov;20(6):771-81.
30. Brown RP, Gerbarg PL, Ramazanov Z. Rhodiola rosea: A Phytomedicinal Overview. HerbalGram 2002; 56:40-52.
31. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000 Oct;7(5):365-71.
32. 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 Apr;7(2):85-9.
33. Shevtsov VA, Zholus BI, Shervarly VI, Vol’skij VB, Korovin YP, Khristich MP, Roslyakova NA, Wikman G. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. 2003 Mar;10(2-3):95-105.
Stress Supplement Sales Trends
So how do you think these increased levels of stress impact sales of stress supplements? If your answer is you think it caused an increase in sales, you are correct. Sales for anxiety/stress relief dietary supplements in 2020 grew 79% from 2018.2 Furthermore, trends seem to indicate that sales of these products won’t be slowing down anytime soon. According to Goldstein Market Intelligence, global sales of stress management supplements are expected to grow at a CAGR of 2.3% during the 2017-2030 period.3
With stress-relief products a starring dietary supplement category, let’s consider the types of nutraceuticals that are directly applicable to stress formulations.
B-Complex Vitamins
The B-complex vitamins are intimately involved in the function of the nervous system, and so can play a role in helping to counter some of the negative effects of stress.4 In fact, the ability of humans to respond to stress can be influenced by nutritional status—including the status of key B vitamins.5
In one study, vitamin B1 (thiamine) and vitamin B6 (pyridoxine) together were found to be especially necessary for workers whose activity is associated with nervous-emotional stress.6 Similar results were seen in a previous study.7
Research on individual B vitamins has also revealed important roles where stress and the nervous system are concerned. This includes vitamin B1 which protected against functional exhaustion,8 pantothenic acid (B5) which supports production of adrenal hormones associated with stress,9 and similar results with other B vitamins. A 12-week study conducted on 60 people found that those consuming one or two forms of vitamin B complex supplements were found to experience fewer work-related symptoms of stress, anger, and fatigue compared to the placebo group.10
Phosphatidylserine
Research has demonstrated that phosphatidylserine (PS) was able to blunt the release of cortisol—the “stress hormone”—in response to exercise stress.11 In some cases, PS supplementation also resulted in improved mood.12-13 A subsequent randomized, double-blind, placebo-controlled study found that, compared to placebo, supplementation with 300 mg PS/day was associated with feeling less stressed (p<0.001) and having a better mood with regard to feeling clear-headed (p<0.02), composed (p<0.03), and confident (p<0.02).14
L-Theanine
The amino acid L-theanine has been shown to increase both serotonin and dopamine production,15 and possibly gamma amino butyric acid (GABA) as well.16
Evidence from human electroencephalograph (EEG) studies show that it also significantly increases brain activity in the alpha frequency band, which indicates that it relaxes the mind without inducing drowsiness. Other research indicates that L-theanine has a significant effect on improving mental alertness while promoting relaxation.17 Additional studies have shown that supplementation with L-theanine resulted in a reduction in some physiological indicators of stress within 15 minutes,18 suppressed the initial stress response of students,19 and significantly reduced anxiety and reduced the blood-pressure increase in high-stress-response adults.20
Apocynum Venetum
Apocynum venetum is an herbal remedy with a long history of use in Traditional Chinese Medicine for soothing the nerves, and for other purposes.21 In a double-blind, randomized trial, individuals with mild depression and symptoms of anxiety were treated with Apocynum venetum leaf extract or placebo at different times over 8 weeks.22 Researchers found that after 8 weeks of treatment, subjects showed a significant decrease in depression scores, and had significant improvements in anxiety.
GABA
GABA is the primary neurotransmitter in the central nervous system for exerting anti-anxiety effects.23 A study investigated the effect of GABA on relaxation and stress in humans, showing that it significantly increased relaxing alpha waves.24 Another study found that GABA supplementation reduced psychological stress induced by an arithmetic task.25 Other research examined the effectiveness of Apocynum venetum and GABA used together, showing that the combination was able to reduce markers of cognitive-induced mental stress.26
Ashwagandha
Ashwagandha (Withania somnifera) is an adaptogenic herb historically used in Asia for treating stress-related health conditions. In one study, an ashwagandha extract was used in chronically stressed people.27 Results indicated subjects experienced a reduction in anxiety as well as serum cortisol (a stress hormone). Overall, the study showed that ashwagandha significantly reduced experiential and biochemical indicators of stress without adverse effects. Other effective adaptogenic herbs include ginseng and Rhodiola.
Panax Ginseng
Panax ginseng root, or ginseng for short, is a traditional Chinese herb which has been used for thousands of years in various aspects of healthcare. It is also one of the most widely researched herbs in modern science with over 5,000 published studies.
Ginseng helps stabilize physiological processes and promote homeostasis, especially in the case of stress and fatigue. This property was seen in two human clinical studies examining the effects of ginseng on mental performance.28-29 The results demonstrated that ginseng root extract improved speed of mental performance within 60 minutes, enhanced performance of mental arithmetic within 60 minutes, reduced feelings of mental fatigue within 60 minutes, quickly reduced feelings of mental fatigue during sustained mental activity, and quickly improved some measures of mental performance.
Rhodiola Rosea Root Extract
Rhodiola rosea root, another adaptogen, has been used for centuries in the traditional systems of healthcare throughout Russia, Scandinavia, and other countries where it was used to increase physical endurance, work productivity, and longevity, as well as to treat fatigue, mood, and promote a healthy nervous system.30
Currently, there are over 500 studies on Rhodiola demonstrating the value of this plant. Human clinical research shows that supplementation with Rhodiola can improve capacity for mental work during stress, support healthy cognitive function during stress, and reduce fatigue during stress.31-33
Conclusion
There are many other nutraceuticals with applications for stress but this overview provides some science-based nutraceutical options for addressing some of the most common issues associated with stress.
References
1. APA: U.S. Adults Report Highest Stress Level Since Early Days of the COVID-19 Pandemic. American Psychological Association. February 2, 2021. Retrieved July 22, 2021 from https://www.apa.org/news/press/releases/2021/02/adults-stress-pandemic
2. Francis E. COVID-19 Stress Drives Anxiety-Reducing Supplement Sales Up 79% In US Since 2018. HBW Insight. 30 Apr 2021. Retrieved July 22, 2021 from https://hbw.pharmaintelligence.informa.com/RS151287/COVID19-Stress-Drives-AnxietyReducing-Supplement-Sales-Up-79-In-US-Since-2018
3. Global Stress Management/Relief Supplements Market Report- Trends, Share, Key Players, Manufacturer’s List, Trade Data, Industry Analysis, By Supplement (Tryptophan, Zinc, Magnesium, Vitamin B, Iron Supplement), By Nature(Herbal & Chemical Based), By Distribution Channel With COVID-19 Impact | Forecast Period 2017-2030. Goldstein Market Intelligence. May 24, 2021. 887 pgs.
4. Whitney E, Rolfes S. Understanding Nutrition, Ninth Edition, Belmont, CA: Wadsworth/Thomson Learning; 2002.
5. Sauberlich HE. Implications of nutritional status on human biochemistry, physiology, and health. Clin Biochem 1984; 17(2):132-42.
6. Bondarev GI, Martinchik AN, Khotimchenko SA, et al. [Correlation of the actual vitamin B1, B2 and B6 consumption with the biochemical indices of their body allowance] Korreliativnaia vzaimosviaz’ fakticheskogo potrebleniia vitaminov B1, B2 i B6 s biokhimicheskimi pokazateliami obespechennosti imi organizma. Vopr Pitan 1986; (2):34-7.
7. Bogdanov NG, Bondarev GI, Piatnitskaia IN, et al. [Vitamin status of diamond cutters] Vitaminnyi status rabochikn, zaniatykh promyshlennoi obrabotkoi almazov. Vopr Pitan 1984; (2):28-31.
8. Vinogradov VV, Tarasov IuA, Tishin VS, et al. [Thiamine prevention of the corticosteroid reaction after surgery] Optimizatsiia tiaminom korticosteroidnoi reaktsii pri khirurgicheskikh vmeshatel’stvakh. Probl Endokrinol 1981; 27(3):11-6.
9. Kutsky R, Handbook of Vitamins and Hormones. New York: Van Nostrand Reinhold Company; 1973:208.
10. Stough C, Scholey A, Lloyd J, et al. The effect of 90 day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. 2011 Oct;26(7):470-6.
11. Fahey TD, Pearl MS. The hormonal and perceptive effects of phosphatidylserine administration during two weeks of resistive exercise-induced overtraining. Biol Sport. 1998;15:135-44.
12. Monteleone P, Maj M, Beinat L, Natale M, Kemali D. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol. 1992;42(4):385-8.
13. Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990 Sep;52(3):243-8.
14. Benton D, Donohoe RT, Sillance B, Nabb S. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci. 2001;4(3):169-78.
15. L-Theanine monograph. Alternative Medicine Review 2005;10(2):136-8.
16. Lu K, Gray MA, Oliver C, et al. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol Clin Exp 2004;19:457–65.
17. Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr 2008;17 Suppl 1:167-8.
18. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol 2007;74(1):39-45.
19. Unno K, Tanida N, Ishii N, et al. Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary α-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav. 2013 Oct;111:128-35.
20. Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012 Oct 29;31:28.
21. Xie W, Zhang X, Wang T, Hu J. Botany, traditional uses, phytochemistry and pharmacology of Apocynum venetum L. (Luobuma): A review. J Ethnopharmacol. 2012 May 7;141(1):1-8.
22. Venetron® brochure, Tokiwa. Summarized in Maypro document “Venetron Clinical Evidence.” Topic: What was the effect of a daily dose of 50 mg of Venetron® in individuals with mild depression over 8 weeks?
23. Kalant H, Roschlau WHE, Eds. Principles of Med. Pharmacology. New York, NY: Oxford Univ Press, 1998.
24. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26(3):201-8.
25. Nakamura H, Takishima T, Kometani T, Yokogoshi H. Psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA) in humans: assessment of stress using heart rate variability and salivary chromogranin A. Int J Food Sci Nutr. 2009;60 Suppl 5:106-13.
26. Yoto A, Ishihara S, Li-Yang J, Butterweck V, Yokogoshi H. The Stress Reducing Effect of γ-Aminobutyric Acid and Apocynum venetum Leaf Extract on Changes in Concentration of Salivary Chromogranin A. Japanese Journal of Physiological Anthropology. 2009 14(3): 55-59.
27. Auddy B, Hazra J, Mitra A, Abedon B, Ghosal S. A Standardized Withania Somnifera Extract Significantly Reduces Stress-Related Parameters in Chronically Stressed Humans: A Double-Blind, Randomized, Placebo-Controlled Study. JANA. 2008;11(1):2008:50-56.
28. 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 Jul;19(4):357-65.
29. 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 Nov;20(6):771-81.
30. Brown RP, Gerbarg PL, Ramazanov Z. Rhodiola rosea: A Phytomedicinal Overview. HerbalGram 2002; 56:40-52.
31. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000 Oct;7(5):365-71.
32. 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 Apr;7(2):85-9.
33. Shevtsov VA, Zholus BI, Shervarly VI, Vol’skij VB, Korovin YP, Khristich MP, Roslyakova NA, Wikman G. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. 2003 Mar;10(2-3):95-105.
