This evidence-based review of chronic stress and the top nutrients, herbs, and other supplements known to help the body counteract its effects, is reproduced with kind permission from the Life Extension Health Concerns and Protocols Library (www.LEF.org). ©1995-2012 Life Extension®. All Rights Reserved. See footnote* for link to all sources.
About Chronic Stress
Although the human body is relatively adept at managing acute physical and/or psychological stressors, chronic psychological stress can produce a variety of adverse effects. Chronic unremitting stress can increase our risk of suffering from a barrage of anxiety- and pressure-related diseases ranging from high blood pressure and dementia to depression…
According to reports by the American Academy of Family Practice and the Russian Department of Family Care, nearly two-thirds of doctor’s office visits are related to stress (Mechanic 1978; Servan-Schreiber 2000; Saleeby 2006).
Regrettably, while chronic stress produces significant adverse health effects, conventional medicine often relies upon psychoactive drugs to mask stressed patients’ symptoms. At the same time, mainstream stress management strategies often fail to address biochemical abnormalities, such as imbalanced adrenal hormone levels, that contribute to the detrimental health effects of chronic stress (Strous 2003; Wolkowitz 1997, 1999).
At the core of chronic stress is deregulation of the hypothalamic-pituitary-adrenal (HPA) axis, an interconnected network of physiologic command terminals that governs the production of stress hormones like cortisol and catecholamines like epinephrine and norepinephrine. Chronic stress leads to desynchronization of the HPA axis and subsequent imbalances in stress hormone levels, a critical feature of stress-related illness….
[To learn more about the mechanics, symptoms and effects of chronic stress, as background for the following review of helpful alternative stress management strategies, see Life Extension’s primer on Stress Management as a Health Concern.]
Alternative Stress Management Strategies
DHEA, an adrenal hormone, counters the action of cortisol, another adrenal hormone, in many tissues (Buoso 2011). The balance between cortisol and DHEA is generally maintained in youth. However, as we age, DHEA levels decline sharply (Zaluska 2009).
The unabated action of cortisol in the presence of declining DHEA levels can contribute to stress-related diseases.
Furthermore, DHEA replacement therapy can restore balance between cortisol and DHEA (Ferrari 2001).
• DHEA has been shown to reduce the negative impact of elevated levels of cortisol on the brain of dementia and Alzheimer’s disease study subjects (Rasmuson 2002).
• The heart benefits as well, with a decline in the incidence of coronary artery disease with DHEA supplementation (Barrett-Connor 1986; Feldman 1998; Shufelt 2010).
• In the context of metabolic syndrome, which is characterized by abdominal obesity, lipid disorders, insulin resistance, and hypertension, DHEA reduces lipid levels, lowers adipose tissue formation and reduces cardiovascular risk (Villareal 2004; Lasco 2001).
• DHEA also has a positive effect on cognitive function and mood (Ferrari 2004; van Broekhoven 2003; Schmidt 2005).
• DHEA appears to be beneficial in those with glucose intolerance and diabetes, lowering average serum glucose levels and averting the destructive effects of diabetes (Kameda 2005; Dhatariya 2005).
• There have been reports of cancer risk reduction with DHEA supplementation as well (Ciolino 2003).
• With regards to age related bone mineral loss, DHEA supplementation has been shown to combat osteoporosis (Villareal 2000).
A great deal of insight into the function of the adrenal glands can be gained through testing blood levels of DHEA and cortisol.
Deviations from the natural rhythm of adrenal function can be detected by an AM / PM cortisol test, in which levels of the adrenal hormone are tested early in the morning and early in the evening of the same day. A DHEA sulfate (DHEA-s) blood test can determine if DHEA levels are sufficient.
Supplemental doses of DHEA typically range from 10 – 25 mg daily for women and 25 – 75 mg daily for men, but should always be determined based upon DHEA-s (DHEA sulfate) blood tests. Life Extension suggests that in order to counter the negative effects of aberrant cortisol production, DHEA-s blood levels should remain between 350 – 490 µg/dL (micrograms per deciliter) for men, and 275 – 400 µg/dL for women.
Safety Caveat: Do not use DHEA if you are at risk for or have been diagnosed as having any type of hormonal cancer, such as prostate or breast cancer.
The hormone melatonin, which is released from the small gland at the base of the brain called the pineal gland, is known for its relationship with the sleep cycle. Melatonin has an antagonistic effect on cortisol, and the circadian rise in melatonin levels at night correlates with a drop in cortisol (Presman 2012). Low levels of melatonin can mean inappropriate and undesirable glucocorticoid signaling during the night when it should be at the lowest.
Chronic, late-night stress, whether physical or psychological, can result in an inappropriately elevated night time cortisol level.
Shift-work is an example of such a stressor (James 2007). This chronic disruption and inappropriate release of cortisol at night may impair the normal circadian corticosteroid output in the morning (Soszynski 1989; Bruls 2000, Pawlikowski 002; Hertoghe 1999).
Melatonin is also a hormone with great penetration into the nucleus of the cells and is one of the most important antioxidant hormones, as it protects cellular (mitochondrial and nuclear) DNA from damage (Reiter 2002).
Melatonin has been found to affect the levels of cortisol and the balance between DHEA and cortisol in circulation (Soszynski 1989; Bruls 2000; Pawlikowski 2002).
Doses differ in individuals but can start as low as 0.3 mg; some may require up to 10 mg daily.
Safety Caveat: If you have asthma or an autoimmune disease, do not use melatonin.
Maintaining Sex Hormone Balance
Imbalances in the sex hormones (testosterone for men, and estrogen and progesterone for women) may exacerbate the detrimental effects of chronic stress.
Some experimental data indicates that having low levels of sex hormones impairs the response to cortisol in the brain (Mitsushima 2008). Over time, this may lead to an over-compensatory increase in stress hormone production by the adrenal glands, which could become damaging.
Likewise, human trials have confirmed that steroid hormones [hormones secreted by the testes, ovaries and adrenal cortex] exert considerable influence over the stress response.
• In a small trial of women who were overcoming cocaine addiction, higher progesterone levels were associated with a blunted stress response to a drug cue (Sinha 2007).
• In another clinical trial, menopausal women treated long-term with hormone replacement therapy (HRT) coped with stress better than non-HRT users in an experimental setting (Patacchioli 2006).
The biological actions of the sex hormone progesterone within the brain are calming, and so age-related declines in progesterone levels may predispose women to anxiety.
Specifically, some metabolites of progesterone have been shown to function as ligands at the GABAA receptor subunit, which is inhibitory upon activation (Majewska 1986).
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NUTRIENTS TO COUNTERACT THE EFECTS OF STRESS
Several members of the B-vitamin family impact varying aspects of stress response physiology.
For example, pantothenic acid [vitamin B 5] is necessary for the synthesis of coenzyme A (CoA), which is integral in the production of cholesterol, and in steroid hormone biosynthesis (Tahiliani 1991; Trumbo 2006). Pantothenic deficiency is rather rare, but it can result in adrenal insufficiency (Murray 1997; Webster 1998; Anon 1980; Plesofsky-Vig 1994).
Another correlation between B-vitamins was revealed in a clinical trial that found that injecting either ACTH (adrenocorticotropic hormone, which promotes cortisol production) or cortisol into healthy subjects for just four days significantly decreased levels of folic acid (aka B9) and B12 (Berg 2006).
These findings suggest that not only are B-vitamins important to promote healthy stress response, but stress itself may lower B-vitamin blood levels.
Therefore, B-vitamin supplementation may ameliorate the effects of stress from multiple angles.
Vitamin C (Ascorbic Acid)
Another crucial vitamin in adrenal function and maintenance of healthy levels of cortisol and DHEA is vitamin C (Bornstein 2004; Morfin 2002). Deficiencies of this vitamin can have profound effects on adrenal function (Brody 2002; Carroll 2000). The benefits of vitamin C are multiple, acting as an anti-inflammatory and co-factor in soft tissue synthesis and repair (Eipper 1992; Hemila 1996; Evans 2008).
In addition, ultra-marathon runners who were given 1,500 mg vitamin C after a race displayed less dramatic elevations in cortisol and epinephrine levels than is typical after such extreme stress (Peters 2001). Moreover, this same study found that vitamin C was able to suppress inflammation in the runners as well.
Calcium, magnesium, sodium and potassium are all macro elements. A macro element means that they are found in our bodies in greater quantities than other elements or minerals.
These four macro elements are important in supporting and maintaining balanced adrenal function (Kobayashi 1996; Carroll 2000). They are important in the formation and release of adrenal hormones.
Manganese, zinc, chromium, and selenium are some of the trace elements that have an impact on the function of the adrenal glands. Research shows that deficiencies in these trace elements can have a negative effect on adrenal function (Golf 1998; Wilborn 2004; Schulz 1998). Note: trace elements such as zinc, selenium and manganese can be obtained as part of a high quality muti-vitamin/mineral supplement.
L-theanine is an amino acid found exclusively in green tea that has traditionally been used to enhance relaxation and improve concentration and learning ability (Vuong 2011; Wakabayashi 2011; Nathan 2006).
L-theanine is chemically related to the neurotransmitter glutamate, and binds to glutamate receptors in the brain (Cho 2008). Unlike glutamate, however, which can cause a state called excitotoxicity [excessive stimulation] that can destroy nerve cells, L-theanine protects brain cells against excitotoxicity, calming the nerve networks in the brain (Kakuda 2002; Nagasawa 2004; Di 2010).
Animal studies verify the behavioral benefits of these biochemical effects. In in vitro studies, L-theanine reduces electrical activity associated with anxiety (Dimpfel 2007).
L-theanine reduces evidence of anxiety and depression in several different animal models of stress (Yin 2011; Heese 2009). In one animal model, L-theanine led to decreases in nearly all frequencies of brainwave activity, indicating a state of calmness and relaxation (Dimpfel 2007).
Moreover, L-theanine has been shown to act synergistically with the GABAergic drug midazolam, a relative of Valium® (Heese 2009).
Brain wave studies have shed some light on the mechanism by which L-theanine may appease anxiety.
• In one study, healthy subjects took a soft drink containing green tea enriched with L-theanine while their brainwave power was measured (Dimpfel 2007). Power was initially reduced in all frequencies and areas during the first hour, indicating relaxation. Later changes indicated both an increase in mental performance and a higher degree of relaxation. In this case, L-theanine seemed to produce desirable increases in attention, accompanied by durable relaxation – that means subjects could concentrate better without being distracted by anxiety.
• Another brainwave study demonstrated that L-theanine significantly increased activity in the frequency band associated with relaxation without inducing drowsiness (Nobre 2008).
• A third trial concluded that L-theanine plays a general role in sustaining attention during a long-term difficult task (Gomez-Ramirez 2009).
Another way to assess stress and anxiety is by measuring vital signs such as heart rate and salivary content of certain proteins that are increased during stress.
Japanese researchers did just that with 12 subjects during a mental arithmetic test given as an acute stressor (Kimura 2007). Results showed that:
• The supplement [L-theanine] reduced heart rate response to the acute stress task, compared with placebo.
• In addition, heart rate variability was improved, a sign that the L-theanine was modulating the sympathetic nervous system, or “fight-or-flight” response.
Omega 3-Fatty Acids (Fish/Krill Oil)
Research indicates that intake of fish/krill oil or omega 3-fatty acids (n-3 EFA, or EFA) can act in an adaptogenic fashion [supports ability to adapt] to help ameliorate the effects of stress (Bradbury 2004; Delarue 2003). Omega-3 fatty acids balance the effects of omega-6 metabolism (Warren 1999; Puri 2007; Maes 2005).
Fatty acid balance is also critical for glucorcorticoid hormone receptor function (Hirata 1980; Hidalgo 1978; Willis 1981).
In recent years omega-3 fatty acids have been documented to be successful in treating those suffering from depression and anxiety disorders, which themselves can be a consequence or an inducer of stress (Logan 2004; Rocha 2010; Silvers 2005).
The phospholipid phosphatidylserine (PS) is found in cell membranes and is a critical component for healthy cellular communication.
Several studies have shown that a diet rich in PS is able to balance the HPA [hypothalamic pituitary adrenal] axis and limit the negative consequences of over-activation of the adrenal cortex (Monteleone 1990; Kelly 1999; Benton 2001; Kimura 2006; Hellhammer 2004).
Phosphatidylserine also helps attenuate the increase in cortisol levels during periods of intense, acute stress (Fahey 1998).
Safety Caveat: Contains soy. The genisten in soy can interfere with the ability of radiation to kill cancer cells, though there are contradictory studies on this issue. When undergoing treatment for cancer consult your healthcare practitioner before using this product.
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Sedative herbs such as hops, passionflower, poppy, and valerian can provide calming effects to reduce stress.
The herbal lemon balm (Melissa officinalis) has been shown in a number of studies to reduce stress. This is yet another herbal that has shown benefit in reducing negative effects of stress on the body (Kennedy 2004 and 2006; Dimpfel 2004).
In a recent small clinical trial including 20 stressed volunteers, a standardized lemon balm extract (Cyracos®) was shown to significantly combat anxiety symptoms and insomnia (Cases 2011). The extract “reduced anxiety manifestations by 18%, ameliorated anxiety-associated symptoms by 15% and lowered insomnia by 42%.”
A class of herbs known as adaptogens are helpful in regulation of the HPA axis.
Dr. Nikolai Lazarev, a noted Russian pharmacologist during the cold war era, coined the term “adaptogenic herb” to describe about 25 of the hundreds of medicinal herbs having particular properties (Kelly 2001). These properties are unique to this class of herbs, making them important for human health.
To be classified as an adaptogen, herbs must have the following three properties:
• There can be no toxicity associated with them;
• They must have a normalizing ability (i.e. the same dose can raise or lower physiologic properties),
• And the mechanisms by which the herbs carry out their effects must be due to more than one physiologic or pharmacologic mechanism (Lipnick 1992; Brekhman: 1969; Saleeby 2006).
Unlike any other compound, adaptogens condition your body to respond favorably to stress.
Adaptogenic herbs can become an important supplement to support a healthy HPA axis stress response. The list of adaptogenic herbs includes about 25 known, and of these several have been studied for their affects on the HPA system.
• Ginseng (Panax ginseng),
• Eleuthero (Eleutherococcus senticosus),
• Rhodiola (Rhodiola rosea),
• Cordyceps (Cordyceps sinensis)
• And Ashwaghanda (Withania somnifera)… to name a few. (Gaffney 2001; Saleeby 2006; Panossian 2005; Kelly 2001; Spasov 2000).
The adaptogenic herb Rhodiola (Rhodiola rosea) has demonstrated in a number of studies improvements in both physical endurance and cognitive performance (De Bock 2004; Spasov 2000; Shevtsov 2003).
Its ability to reduce fatigue associated with stress is documented in well-designed research papers (Olsson 2009; Spasov 2000; Panossian 2009).
The apparent mechanism of action of Rhodiola is related to its ability in assisting neurotransmitter transport in the brain and the blunting of catecholamine release (Stanchev 1987; van Diermen 2009).
A large, phase III placebo-controlled clinical trial was conducted in Sweden in 2009, studying participants aged 20-55 years with a diagnosis of stress-related fatigue (Olsson 2009). Subjects taking the Rhodiola extract:
• Had significantly lower cortisol responses to chronic stress than did the placebo recipients –
• And as a result they had lower scores on scales of burnout and improved performance on cognitive testing.
Safety Caveat: Individuals with manic or bipolar disorder should not use rhodiola. Take rhodiola extract early in the day if it interferes with your sleep.
Ashwagandha, also known as Withania somnifera, is an important Ayurvedic medicinal herb. It has many uses in traditional Indian medicine such as treatments for stress, fatigue, pain, diabetes, GI and rheumatologic disorders (Mishra 2000).
Ashwagandha has shown promise in neuroprotection as scientists have discovered that this adaptogenic herb prevents damage to neurons and improves neurological function in the face of stress (Cooley 2009; Tohda 2005; Choudhary 2004).
Additionally, data suggests that Ashwagandha may reduce the harmful effects of stress on male reproductive capacity (Ahmad 2010).
A double blind, randomized, placebo-controlled clinical trial assessed the effects of ashwagandha in 130 chronically stressed subjects (Auddy 2008). Over a 60-day period, doses ranging from 125 mg to 500 mg daily of a patented ashwagandha extract (Sensoril®):
• Significantly improved scores on a standardized measurement of stress intensity,
• And also favorably modulated several biomarkers associated with cardiovascular health, including C-reactive protein and blood pressure.
• Moreover, at the end of the study period subjects who received 500 mg of ashwagandha daily had cortisol levels nearly 30% lower than subjects who took a placebo, and their DHEA-s levels were significantly higher as well.
Probably the most recognized of the adaptogen herbs in the West is Ginseng (Panax ginseng). There are 11 species of this medicinal herb, P. ginseng being among the most widely studied (Chen 2004; Huang 1999).
American Ginseng (Panax quinquefolius) is another species within the Panax genus that shares medicinal properties (Chan 2000).
Siberian ginseng (Eleutherococcus senticosus), while not technically a true ginseng botanical, has similar beneficial properties and is closely related to the Panax family of plants (Davydov 2000).
A wealth of studies exist showing stress reducing properties of true ginseng and the other ginseng related herbals (Barton 2010; Ma 2008). For example the isolated polysaccharides from P. ginseng have demonstrated anti-fatigue properties in one recent study (Wang 2010).
American ginseng extract shows a reduction in oxidative endothelial damage due to diabetes (Sen 2011; Amin 2011). Anti-depressive effects and the positive modulation that benefits the HPA axis is outlined in a research paper on protective ginsenosides in Panax and other ginseng plants showing usefulness in the management of chronic stress (Liu 2011; Cao 2011).
Licorice (Glycyrrhiza glabra and G. uralensis)
A mainstay in Traditional Chinese Medicine (TCM), licorice extracts may be of benefit for those who have reached the exhaustion stage and are no longer producing sufficient cortisol.
Licorice has the ability to decrease the breakdown or metabolism of hydrocortisone by the liver, thus increasing the amount of cortisol in circulation and reducing the strain on the adrenal glands to produce it (Methlie 2011).
The combination of low doses of licorice with supplemental DHEA may help balance the HPA axis (Palermo 2004).
It is important to understand that licorice may not be ideal for everyone dealing with day-to-day stress. In high doses over prolonged periods licorice may cause electrolyte imbalance (hypokalemia) and elevations in blood pressure, a syndrome called hypermineralocorticoidism (Schambelan 1994).
Due to its ability to increase cortisol levels, licorice is best reserved for those individuals who are experiencing fatigue due to chronic stress and also have low cortisol levels.
* Sources: All stress management references cited in this article can be found HERE.
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