Psychological stress can have a dramatic effect on various aspects of our health. It can impair memory, reduce mental well-being, wreak havoc on the digestive tract, destroy cardiovascular health and reduce overall lifespan. With the poor economy looming over our heads, there has never been a more stressful time for many of us alive today.
In a three part series in this newsletter, I will discuss the destructive effects of stress on various systems of the body as well as natural stress-reducing supplement regimens. In this first part of the series, I will discuss the ways in which chronic stress can impair memory and how stress is linked to depression.
Chronic Stress and Memory
Stress is known to strongly influence the prefrontal cortex (PFC), a key brain region controlling cognition and emotion. Interestingly, acute, short-term stress can affect corticosteroid stress hormones and the PFC in such a way as to enhance learning and memory. This makes sense due to the fact that when a person is exposed to a dangerous stressor heightened vigilance is essential to survival. However, long-term, chronic stress can have the opposite effect and can damage cognition, emotion and memory.1
One of the reasons stress is so destructive to memory revolves around the adrenal glands’ production of excessive cortisol, which occurs during chronic stress. High cortisol levels, when maintained for a long time, are known to be linked to poor memory. This has been shown in a number of studies including a recent study where researchers investigated 37 unmedicated, non-delusional patients with major depression and 18 healthy controls. The subjects underwent psychiatric ratings, hourly assessments of cortisol activity over 24 hours, and neuropsychological assessments.
The study authors found that greater cortisol levels in the subjects were related to poorer memory performance. High cortisol levels also were significantly related to impaired verbal memory (paragraph recall).2
Perhaps one of the most graphic illustrations of how stress affects cognition involves Alzheimer’s disease, which is thought to develop as a result of over-production and aggregation of beta-amyloid (Abeta) peptides in the brain. Researchers have found that individuals suffering from chronic stress are at an increased risk for developing Alzheimer’s. Furthermore, in a recent rodent study, researchers induced chronic psychosocial stress in rats then administered Abeta to the animals. The effect of chronic stress on the severity of Abeta-induced spatial learning and memory impairment was tested by three approaches: behavioral testing in a water maze, in vivo electrophysiological recording in anesthetized rats, and analysis to determine protein levels of learning- and memory-related molecules. The results indicated that a marked impairment of learning and memory developed when stress was combined with Abeta, more so than that caused by Abeta alone.
Additionally, there was a significantly greater impairment of early-phase long-term potentiation in chronically stressed/Abeta-treated rats than in either the stressed or Abeta-treated rats.3 Long-term potentiation (LTP) refers to a long-lasting improvement in communication between two neurons that results from stimulating them simultaneously. Neurons use chemical synapses to communicate with each other, and it is thought that memories are encoded by modification of synapses. LTP, therefore, is widely considered to be one of the major cellular mechanisms involved in learning and memory, from the relatively simple learning processes occurring in all animals, to the more complex cognition in humans. Therefore the fact that stress combined with the formation of Abeta proteins impairs LTP indicates that stress plays a destructive role in learning and memory through inhibiting the beneficial effects of LTP.
Stress’s destructive effect on neuronal communication translates into decreased cognitive performance as evidenced by a study of 65 subjects suffering from work-stress-related burnout and 65 demographically matched, healthy reference subjects. Among burnout cases, lower diurnal cortisol variability was related to slower performance in several tests.4
Stress also seems to compound the adverse effects on learning and memory that occur after intake of a high-fat diet. Young adult rodents were exposed to chronic psychosocial stress and/or a high-fat diet for 3 months. In a water maze, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied daily until the animals reached what the researchers called days to criterion (DTC), which is the number of days that the animals took to make zero errors in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC.
The results indicated that the groups exposed to chronic stress, high-fat diet and both chronic stress and high-fat diet showed impaired learning as indicated by committing significantly more errors than the control group. In memory tests, chronic stress, high-fat diet and chronic stress/high-fat diet groups showed significantly impaired performance compared to the control group. Additionally, the group exposed to both stress and a high-fat diet was the only group that showed significantly impaired performance in memory tests on the fifth training day, suggesting more severe memory impairment in that group. Furthermore, DTC value (the number of days that the animals take to make zero errors in two consecutive days) for all the above groups indicated that chronic stress or high-fat diet alone resulted in a mild impairment of spatial memory, but the combination of chronic stress and high-fat diet resulted in a more severe and long-lasting memory impairment.5
Furthermore, humans often have to perform complex social cognitive tasks while under stress (such as during a social conflict). The link between stress and cognitive dysfunction is further cemented by the fact that the brain regions responsible for social cognitive tasks are target regions for stress hormones.6
Stress and Depression
Cognitive dysfunction and high cortisol levels often occur side-by-side in depressed individuals. Cortisol’s actions occur via mineralocorticoid and glucocorticoid receptors, which occur in the highest density in the hippocampus, a brain area closely related to cognitive function. Scientists recently examined this connection in 52 medication-free patients with major depression (37 women, 15 men) and 50 healthy control subjects, matched for age, gender, and years of education. The researchers applied several neuropsychological tests and measured salivary cortisol levels four times throughout the same day.
The researchers found that compared with healthy subjects, depressed patients had significantly higher cortisol levels and were impaired in verbal memory, visuospatial memory, working memory, and selective attention. In depressed patients, but not in healthy control subjects, the study authors found that the higher the salivary cortisol levels the greater the impairment of verbal memory and visuospatial memory.7 There was also a link between higher cortisol levels in the depressed patients and impaired executive function, a term used by psychologists and neuroscientists to describe brain processes responsible for planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions, and selecting relevant sensory information.
According to the researchers, “Cognitive deficits, especially those closely related to hippocampus function, appear to be related to cortisol secretion in depressed patients. Elevated cortisol may downregulate mineralocorticoid and glucocorticoid receptors in the hippocampus, which could, in part, be responsible for cognitive deficits in depressed patients.”
Three strategies can be employed to reduce the harmful effects of stress on the body. The first step is to take a salivary hormone test (adrenal function panel) in order to measure levels of cortisol in the body and to determine the state of the adrenal glands.
Based on the results of the test, chronically excessive cortisol levels can be lowered using a combination of Relora® (a proprietary blend of a patented extract from Magnolia officinalis bark and a patent-pending extract from Phellodendron amurense bark) and Sensoril™ (a patented proprietary extract of roots and leaves from Withania somnifera Dunn, known as Ashwagandha. Both Relora and Sensoril are found in the formula Cortisol Control.
Studies have shown that these two compounds can alleviate high cortisol’s effects on the body. Fifty stressed people were given 200 mg Relora three times per day for two weeks. Post-trial analysis revealed that 82 percent found Relora effective in controlling stress-induced symptoms, such as depression, anxiety, irritability, emotional ups and downs, concentration difficulties and restlessness. Seventy-eight percent reported increased relaxation, while 74 percent had more restful sleep.8
In another trial 12 stressed subjects took Relora for two weeks. Salivary DHEA and cortisol measurements were taken. Morning salivary cortisol levels (when cortisol levels are normally highest) dropped 37 percent, while DHEA levels rose 227 percent. Previously abnormal cortisol/DHEA levels returned to normal in all subjects by the study’s end.8
Sensoril, a carefully balanced formulation of the key compounds that provide Ashwagandha’s immunomodulating and anti-stress activity, can work synergistically with Relora. By optimizing the ratio of oligosaccharides to polysaccharides in the Ashwagandha, this formulation protects the withanolides from digestive inactivation and enhances their absorption. Ashwagandha has been used in Ayurvedic medicine for many centuries to promote resistance to stress and has been reported to enhance mental function and memory.
Sensoril’s extracts have been subject to a wide range of tests to measure anti-stress activity. In one experiment, rats were exposed to severe overcrowding conditions or tactile stress (continuous poking), and then given morphine. Seventy percent of the tactile-stressed and 100 percent of the overcrowding-stressed control rats developed convulsions, and 80 percent and 90 percent died, respectively. Yet only 10 percent of the tactile-stressed rats and 10 percent of the overcrowding-stressed rats given morphine plus Sensoril developed convulsions, while 0 percent and 10 percent died.9
Severe stress causes adrenal glands to enlarge, and their vitamin C and corticosterone content drops. Another experiment showed that when stress is induced in rats, the rodents given Sensoril had smaller adrenal glands with more corticosterone in them than the unstressed control rats, and almost as much vitamin C.9
Another effective strategy to control stress, thereby improving cognitive function, is to supplement with the adaptogens Eleutherococcus senticosus, Manchurian Thorn Tree (Aralia manchurica), and Schisandra (Schisandra chinensis), all found in AdaptaPhase® I.
Eleutherococcus has been traditionally used for modulation of stress and fatigue as well as immune-stimulating action. In a single-blind, placebo-controlled crossover study, supplementation with Eleutherococcus was evaluated in regards to maximal working capacity in adolescent males. The results indicated a 23.3 percent increase in total work after Eleutherococcus supplementation.10 Animal studies measuring forced swimming time show that supplementation with Eleutherococcus inhibits stress-induced cortisol increase and stress-induced immune suppression and improves endurance demonstrated by increased swimming time.11
Schisandra is another adaptogenic traditional Chinese botanical. Evidence suggests that adaptogens such as Schisandra support the stress response both by affecting the sympathetic-adrenal response with short term administration as well as supporting the hypothalamic-pituitary-adrenal axis with longer-term administration.12-13 Studies using animal models confirm that Schisandra can reduce elevated serum corticosterone levels.14
Aralia manchurica (Manchurian Thorn Tree) has historically been used in Russia as an adaptogen for fatigue, weakness, headaches, depression, immune support, and stress-overload. One study showed a 90 percent success rate using this herb in individuals with stress overload and weakness.15Aralia has also been shown to decrease blood glucose levels in animal studies.16
Chronic stress is an under-recognized factor in the development of cognitive impairment. Furthermore, stress also is linked to depression. Therefore, employing a supplement regimen that combines a cortisol-lowering supplement (Cortisol Control) with adaptogenic support (AdaptaPhase 1) can be an effective strategy to manage stress and preserve memory.
1. Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc Natl Acad Sci USA. 2009 Aug 18;106(33):14075-9.
2. Gomez RG, Posener JA, Keller J, DeBattista C, Solvason B, Schatzberg AF. Effects of major depression diagnosis and cortisol levels on indices of neurocognitive function. Psychoneuroendocrinology. 2009 Aug;34(7):1012-8.
3. Srivareerat M, Tran TT, Alzoubi KH, Alkadhi KA. Chronic psychosocial stress exacerbates impairment of cognition and long-term potentiation in beta-amyloid rat model of Alzheimer’s disease. Biol Psychiatry. 2009 Jun 1;65(11):918-26.
4. Osterberg K, Karlson B, Hansen AM. Cognitive performance in patients with burnout, in relation to diurnal salivary cortisol. Stress. 2009;12(1):70-81.
5. Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA. Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats. Behav Brain Res. 2009 Dec 1;204(1):117-23.
6. Smeets T, Dziobek I, Wolf OT. Horm Behav. Social cognition under stress: Differential effects of stress-induced cortisol elevations in healthy young men and women. 2009 Feb 6. Published Online Ahead of Print.
7. Hinkelmann K, Moritz S, Botzenhardt J, Riedesel K, Wiedemann K, Kellner M, Otte C.Biol Psychiatry. Cognitive Impairment in Major Depression: Association with Salivary Cortisol. 2009 Aug 25. Published Online Ahead of Print.
8. LaValle J and Hawkins, E. Relora—The Natural Breakthrough to Losing Stress-Related Fat and Wrinkles. North Bergen, NJ: Basic Health Publications; 2003:16.
9. Bhattacharya S. et al. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother Res. 1987;1: 32-37.
10. Kimura Y, Sumiyoshi M. Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice. J Ethnopharmacol. 2004 Dec;95(2-3):447-53.
11. Upton R, ed. Schisandra Berry: Analytical, quality control, and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999;1-25.
12. Panossian A, Wagner H. Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother Res. 2005 Oct;19(10):819-38.
13. Lee S, Kim DH, Jung JW, et al. Schizandra chinensis and Scutellaria baicalensis counter stress behaviors in mice. Phytother Res. 2007 Dec;21(12):1187-92.
14. Chiu PY, Leung HY, Ko KM. Schisandrin B Enhances Renal Mitochondrial Antioxidant Status, Functional and Structural Integrity, and Protects against Gentamicin-Induced Nephrotoxicity in Rats. Biol Pharm Bull. 2008 Apr;31(4):602-5.
15. Martinez B, Staba EJ. The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats. Jpn J Pharmacol. 1984 Jun;35(2):79-85.
16. Wang L, Tu YC, Lian TW, et al. Distinctive antioxidant and antiinflammatory effects of flavonols. J Agric Food Chem. 2006 Dec 27;54(26):9798-804.
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