Life Extension Magazine December 2005
Cortisol, Stress, and Health
By Edward R. Rosick, DO, MPH, MS
By Edward R. Rosick, DO, MPH, MS
Supplements to Combat Cortisol
Exercise and meditation are two important modalities that may help many individuals manage stress-filled lives. In addition, studies suggest that effective natural supplements, such as vitamin C, fish oil, phosphatidylserine, and herbal adaptogens, may help keep the HPA axis in equilibrium, reduce elevated cortisol levels, and help optimize health.
Besides its beneficial effects in maintaining proper immune system function, vitamin C has been shown to help modulate high levels of cortisol brought about by stress. A study in 2001 examined the effects of supplemental vitamin C on high cortisol levels brought about by physical stress in marathon runners.31 In a randomized, placebo-controlled study, ultramarathon runners were given 500 mg a day of vitamin C, 1500 mg a day of vitamin C, or a placebo seven days before a marathon, the day of the race, and two days after the race. Researchers found that athletes who took 1500 mg per day of vitamin C had significantly lower post-race cortisol levels then those taking either 500 mg a day or placebo.31
Another study published in the journal Psychopharmacology reviewed evidence showing that vitamin C can reduce high cortisol levels brought about by psychologically induced stress.32 In a randomized, double-blind, placebo-controlled trial, researchers gave 3000 mg per day of vitamin C or a placebo to 120 volunteers who were subjected to psychological stress through the Trier Social Stress Test (TSST), a commonly used assessment tool in psychological research that simulates public speaking and arithmetic tests to induce stress and raise cortisol levels. Subjects who took vitamin C had lower blood pressure, subjective stress, and cortisol measures compared to those who were given placebo.
In a number of clinical tests, fish oil has been shown to reduce cardiovascular risk in women and men. Preliminary research has shown that fish oil may help individuals cope with psychological stress and lower their cortisol levels. In a study published in 2003, researchers gave seven study volunteers 7.2 grams per day of fish oil for three weeks and then subjected them to a battery of mental stress tests.33 Blood tests showed that these psychological stressors elicited changes in the subjects’ heart rate, blood pressure, and cortisol levels. After three weeks of fish oil supplementation, however, the rise in cortisol levels secondary to stress testing was significantly blunted, leading the authors to conclude that supplementation with omega-3 fatty acids from fish oil “inhibits the adrenal activation elicited by a mental stress, presumably through effects exerted at the level of the central nervous system.”33
Another supplement that has been shown to be useful in combating the deleterious effects of stress is phosphatidylserine. This phospholipid constitutes an essential part of biological cellular membranes. For more than 10 years, studies have shown that phosphatidylserine is able to cut elevated cortisol levels induced by mental and physical stress. In one early study, 800 mg per day given to healthy men significantly blunted the rise in cortisol caused by physical stress.34 Another paper reported that even small amounts of supplemental phosphatidylserine (50-75 mg administered intravenously) could blunt cortisol increases secondary to physical stressors.35 In this study, eight healthy men had their blood drawn before and after physical stress induced by riding a bicycle ergometer. While all subjects showed increased cortisol levels, pretreatment with the 50- or 75-mg dose of phosphatidylserine significantly blunted cortisol response to the physical stressor.35
Finally, a study published in 2004 examined phosphatidylserine’s effects on endocrine and psychological responses to mental stress.36 The stressor used was the Trier Social Stress Test (TSST), which consists of 15 minutes of psychological stress induced via a mock job interview, followed by a mental arithmetic challenge. This double-blind study followed 40 men and 40 women, aged 20-45, for three weeks. The subjects were given either phosphatidylserine (either 400 or 600 mg daily) or a placebo before taking the TSST. Phosphatidylserine was effective in blunting the cortisol response to stressors, with those taking 400 mg daily (but not, surprisingly, 600 mg) of phosphatidylserine showing a significantly decreased cortisol response. The authors concluded that phosphatidylserine helped dampen the effects of stress on the pituitary-adrenal axis, and may have a role in managing stress-related disorders.36
Plant-derived adaptogens can be a very useful in combating the mental and physical rigors of our modern lifestyle. Adaptogens work by modulating the levels and activity of hormones and brain neurochemicals that affect everything from cardiac activity to pain perception. For any herb or substance to be properly classified as an adaptogen, it should:
One such herbal adaptogen is Rhodiola rosea, or rhodiola. In traditional Asian and European medicine, this herb has been used for centuries to increase physical endurance and longevity, as well as to manage fatigue, depression, and impotence. Rhodiola’s positive effects are thought to be mediated through the actions of rosavins and salidrosides, chemical compounds found in the plant’s roots. Multiple studies from the former Soviet Union have demonstrated rhodiola’s effectiveness in combating both physically and psychologically stressful conditions.37
Another herb that serves as an adaptogen is ginseng, which has been used throughout Asia since antiquity. It is important to note that ginseng is the name given to three different plants used as adaptogens. The most widely used ginseng is Panax ginseng, also known as Korean, Chinese, or Asian ginseng. Panax quinquefolium—or American ginseng—is also considered a “true” ginseng. However, Siberian ginseng (Eleutherococcus senticosus), while commonly referred to as ginseng, is not a true ginseng but a closely related plant. Yet no matter what the genus or species, all three of these plants have experimental evidence backing their adaptogenic claims. Animal studies have shown that ginsenosides, bioactive compounds in ginsengs, improve the sensitivity of the HPA axis to cortisol.38,39 In addition, studies suggest that all three plants provide protection against both physical and psychological stresses.38,39
Finally, another plant that deserves mention as an adaptogen is ginkgo biloba. For the last 5,000 years, leaves of the ginkgo tree have been used to treat various medical conditions. While ginkgo is currently used to help combat the debilitating effects of memory decline and dementia,40-42 emerging evidence suggests that it may be useful in treating the impact of stress and elevated cortisol levels. A recent double-blind, placebo-controlled study published in the Journal of Physiology and Pharmacology examined ginkgo’s effects in modulating cortisol and blood pressure levels in 70 healthy male and female subjects.43 When subjected to physical and mental stressors, subjects who were given 120 mg per day of a standardized ginkgo extract saw smaller increases in their cortisol levels and blood pressure then did their counterparts who were given a placebo.
Raising DHEA Levels
While cortisol levels stay the same or even increase as we age, levels of another vitally important hormone, DHEA, decrease with each passing year. This relationship between cortisol and DHEA has led some to suggest that these adrenal hormones may play a significant role in the aging process and its associated negative health effects. A recent paper in the European Journal of Endocrinology examined the pathophysiological correlates of age-related changes in the HPA axis.44 The authors showed that the cortisol/DHEA ratio increases significantly as one ages, and is even higher in elderly patients who suffer from dementia. Supplemental DHEA, however, enhances the brain’s resistance to stress-mediated changes, maintains functional abilities, and protects against age-related diseases. The authors concluded, “the changes of the hormonal balance [between cortisol and DHEA] occurring in aging may contribute to the onset and progression of the aging-associated neurogenerative diseases.”44
Exercise, stress management techniques such as relaxation and meditation, and nutritional supplements can help you manage stress and lower cortisol to promote optimal health and longevity. The following are scientifically supported techniques that can help support a healthy response to stress.
1. Behavioral techniques to lower stress and manage high cortisol levels
2. Supplements to reduce high cortisol levels secondary to stress
1. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002 Oct;53(4):865-71.
2. Carrasco GA, Van de Kar LD. Neuroendocrine pharmacology of stress. Eur J Pharmacol. 2003 Feb 28;463(1-3):235-72.
3. De Kloet ER. Hormones and the stressed brain. Ann NY Acad Sci. 2004 Jun;1018:1-15.
4. Kudielka BM, Buske-Kirschbaum A, Hellhammer DH, Kirschbaum C. HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender. Psychoneuroendocrinology. 2004 Jan;29(1):83-98.
5. Bauer ME. Stress, glucocorticoids and ageing of the immune system. Stress. 2005 Mar;8(1):69-83.
6. Valenti G. Neuroendocrine hypothesis of aging: the role of corticoadrenal steroids. J Endocrinol Invest. 2004;27(6 Suppl):62-3.
7. Ferrari E, Mirani M, Barili L, et al. Cognitive and affective disorders in the elderly: a neuroendocrine study. Arch Gerontol Geriatr Suppl. 2004;(9):171-82.
8. Selye H. A syndrome produced by diverse nocuous agents. 1936. J Neuropsychiatry Clin Neurosci. 1998;10(2):230-1.
9. Selye H. The general adaptation syndrome and the diseases of adaptation. J Clin Endo. 1946;6:117-20.
10. Schedlowski M, Wiechert D, Wagner TO, Tewes U. Acute psychological stress increases plasma levels of cortisol, prolactin and TSH. Life Sci. 1992;50(17):1201-5.
11. Schulz P, Kirschbaum C, Prubner J, Hellhammer D. Increased free cortisol secretion after awakening in chronically stressed individuals due to work overload. Stress Med. 1998;14:91-7.
12. Lac G, Chamoux A. Elevated salivary cortisol levels as a result of sleep deprivation in a shift worker. Occup Med (Lond). 2003 Mar;53(2):143-5.
13. Cohen S. Psychological stress and susceptibility to upper respiratory infections. Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 2):S53-8.
14. Buljevac D, Hop WC, Reedeker W, et al. Self reported stressful life events and exacerbations in multiple sclerosis: prospective study. BMJ. 2003 Sep 20;327(7416):646.
15. Locke GR, III, Weaver AL, Melton LJ, III, Talley NJ. Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study. Am J Gastroenterol. 2004 Feb;99(2):350-7.
16. Lea R, Whorwell PJ. Psychological influences on the irritable bowel syndrome. Minerva Med. 2004 Oct;95(5):443-50.
17. van der PG, Antoni MH, Heijnen CJ. Elevated basal cortisol levels and attenuated ACTH and cortisol responses to a behavioral challenge in women with metastatic breast cancer. Psychoneuroendocrinology. 1996 May;21(4):361-74.
18. Reiche EM, Nunes SO, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol. 2004 Oct;5(10):617-25.
19. Allison TG, Williams DE, Miller TD, et al. Medical and economic costs of psychologic distress in patients with coronary artery disease. Mayo Clin Proc. 1995 Aug;70(8):734-42.
20. Ohlin B, Nilsson PM, Nilsson JA, Berglund G. Chronic psychosocial stress predicts long-term cardiovascular morbidity and mortality in middle-aged men. Eur Heart J. 2004 May;25(10):867-73.
21. Grundman M, Thal LJ. Treatment of Alzheimer’s disease: rationale and strategies. Neurol Clin. 2000 Nov;18(4):807-28.
22. Mayeux R, Sano M. Treatment of Alzheimer’s disease. N Engl J Med. 1999 Nov 25;341(22):1670-9.
23. Ferrari E, Casarotti D, Muzzoni B, et al. Age-related changes of the adrenal secretory pattern: possible role in pathological brain aging. Brain Res Brain Res Rev. 2001 Nov;37(1-3):294-300.
24. Raber J. Detrimental effects of chronic hypothalamic-pituitary-adrenal axis activation. From obesity to memory deficits. Mol Neurobiol. 1998 Aug;18(1):1-22.
25. Lee AL, Ogle WO, Sapolsky RM. Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord. 2002 Apr;4(2):117-28.
26. Carlson LE, Sherwin BB. Relationships among cortisol (CRT), dehydroepiandrosterone-sulfate (DHEAS), and memory in a longitudinal study of healthy elderly men and women. Neurobiol Aging. 1999 May;20(3):315-24.
27. Wilson RS, Evans DA, Bienias JL, et al. Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology. 2003 Dec 9;61(11):1479-85.
28. Traustadottir T, Bosch PR, Matt KS. The HPA axis response to stress in women: effects of aging and fitness. Psychoneuroendocrinology. 2005 May;30(4):392-402.
29. MacLean CR, Walton KG, Wenneberg SR, et al. Effects of the Transcendental Meditation program on adaptive mechanisms: changes in hormone levels and responses to stress after 4 months of practice. Psychoneuroendocrinology. 1997 May;22(4):277-95.
30. Cruess DG, Antoni MH, McGregor BA, et al. Cognitive-behavioral stress management reduces serum cortisol by enhancing benefit finding among women being treated for early stage breast cancer. Psychosom Med. 2000 May;62(3):304-8.
31. Peters EM, Anderson R, Nieman DC, Fickl H, Jogessar V. Vitamin C supplementation attenuates the increases in circulating cortisol, adrenaline and anti-inflammatory polypeptides following ultramarathon running. Int J Sports Med. 2001 Oct;22(7):537-43.
32. Brody S, Preut R, Schommer K, Schurmeyer TH. A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress. Psychopharmacology (Berl). 2002 Jan;159(3):319-24.
33. Delarue J, Matzinger O, Binnert C, Schneeiter P, Chiolero P, Tappy L. Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Diabetes Metab. 2003 Jun;29(3):289-95.
34. 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.
35. 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.
36. Hellhammer J, Fries E, Buss C, et al. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress. 2004 Jun;7(2):119-26.
37. Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev. 2001 Jun;6(3):293-302.
38. Kelly GS. Nutritional and botanical interventions to assist with the adaptation to stress. Altern Med Rev. 1999 Aug;4(4):249-65.
39. Nocerino E, Amato M, Izzo AA. The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia. 2000 Aug;71 Suppl 1:S1-5.
40. Kanowski S, Herrmann WM, Stephan K, Wierich W, Horr R. Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry. 1996 Mar;29(2):47-56.
41. Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997 Oct 22;278(16):1327-32.
42. Le Bars PL, Kieser M, Itil KZ. A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia. Dement Geriatr Cogn Disord. 2000 Jul;11(4):230-7.
43. Jezova D, Duncko R, Lassanova M, Kriska M, Moncek F. Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761) in healthy volunteers. J Physiol Pharmacol. 2002 Sep;53(3):337-48.
44. Ferrari E, Cravello L, Muzzoni B, et al. Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates. Eur J Endocrinol. 2001 Apr;144(4):319-29.
45. Epel ES, McEwen B, Seeman T, et al. Stress and body shape: Stress-induced cortisol secretion is consistently greater among women with central fat. Psychosomatic Med. 2000 Sept;62(5):623-32.
46. Gluck ME, Geliebter A, Lorence M. Cortisol stress response is positively correlated with central obesity in obese women with binge eating disorder (BED) before and after cognitive-behavioral treatment. Ann NY Acad Sci. 2004 Dec;1032:202-7.