What is Stress?
Stress generally occurs when external stimuli disturb the dynamic balance of the body’s physiological processes. A specialized signaling network called the HPA axis coordinates the body’s stress response.
Acute stress helps prime the body to respond to immediate, transient threats. Intermittent mild stress, such as exercise, is healthy and promotes positive adaptive changes. Chronic stress, however, causes maladaptive responses and dysregulated HPA axis function. It can contribute to many health problems by disrupting the circadian rhythm, promoting inflammation, altering the microbiome, and causing epigenetic changes.
Natural interventions such as adaptogens, L-theanine, B vitamins, and omega-3 fatty acids may help relieve stress and restore normal HPA axis function.
How Can I Determine If Stress is Affecting My Health?
- Blood tests (including cortisol, dehydroepiandrosterone [DHEA], salivary alpha-[a] amylase, and immunoglobulin A [IgA])
- Heart rate variability
What Dietary and Lifestyle Changes Can Help Relieve Stress?
- Cognitive-behavioral therapy
- Meditation and mindfulness
- Maintain good sleep hygiene, sufficient sleep duration, and consistent sleep patterns
- Maintain sex hormone balance
- Eat more fruits and vegetables
- Eat breakfast regularly
- Minimize caffeine and alcohol intake
Can Medications Help Relieve Stress?
Most cases of stress can be managed with dietary and lifestyle interventions. However, in more severe cases when stress is contributing to other conditions such as anxiety or insomnia, medications may be appropriate for short-term use to temporarily address the stress-related condition(s). It is important to understand that medications do not eliminate stress or the causes of stress, but simply provide temporary relief from some of the symptoms caused by stress.
- Antidepressants and anti-anxiety medications such as selective serotonin reuptake inhibitors (SSRIs) (eg, Prozac and Zoloft)
- Beta-blockers (eg, propranolol)
- Sedatives such as benzodiazepines (eg, Valium and Klonopin)
What Natural Interventions May Help Relieve Stress?
- B vitamins. B vitamin deficiencies are linked with multiple neuropsychiatric disorders. Supplementation with B vitamins has been shown to relieve stress and support normal HPA axis function.
- Vitamin C. Low intake and circulating levels of vitamin C are correlated with symptoms of depression and anxiety. Increasing vitamin C levels via supplementation has been shown to reduce symptoms.
- Omega-3 fatty acids. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil, may help prevent and treat stress, anxiety, and depression.
- L-theanine. L-theanine, an amino acid found in tea, has been shown to reduce perceived stress and physiological markers of the stress response.
- Bioactive milk peptides. Peptides found in milk, such as a-lactalbumin and casein, may support healthy neurological function, improve mood, and promote sleep.
- Probiotics and prebiotics. Probiotics and prebiotics can improve the balance of gut bacteria and have a positive impact on stress response. Probiotics may lower stress reactivity and anxiety, and improve mood, memory, and cognition.
- Adaptogens. Adaptogenic herbs help support homeostasis in the body and can be used to relieve fatigue, improve cognitive function and mood, and support the immune system.
- Magnolia and phellodendron. This herbal combination has been found to reduce stress and stress-related weight gain.
- Holy basil. A number of clinical and preclinical studies have demonstrated holy basil’s ability to improve mood and cognition.
- Ashwagandha. Ashwagandha has been shown to relieve stress, improve stress-related eating behaviors, and promote weight loss.
- Lemon balm. Lemon balm has been found to improve mood and cognition and relieve symptoms of anxiety and insomnia.
- Other adaptogens that may help relieve stress include bacopa, saffron, ginseng, rhodiola, cordyceps, and others.
- Other natural interventions may help relieve stress, including phosphatidylserine, L-tryptophan, melatonin, and dehydroepiandrosterone (DHEA).
Over the course of evolutionary time, the human body has become reliant on the acute stress response to overcome short-term adversity. But human
physiology is simply not adapted to the relatively modern phenomenon of
unrelenting low-level stress. Consequently, we now face an epidemic of
health problems to which chronic stress is a contributing factor.1,2
A key feature of chronic stress is dysregulation of the
hypothalamic-pituitary-adrenal (HPA) axis, a network of signaling centers
in the brain and body that modulates our physiological response to stress.
Normal activation of the HPA axis is necessary for healthy adaptive
responses to stressors, but chronic activation leads to a maladaptive
stress response marked by changes in the release and activity of the stress
hormone, cortisol, which contributes to stress-related illness.2,3 Interactions between the HPA axis and the central nervous
system, immune system, and gut microbiome contribute the wide-ranging
effects of stress on overall health.4,5
The good news is that making healthy lifestyle decisions and adhering to a
healthy diet can enhance resistance to the detrimental effects of chronic
stress.4-6 In this protocol, you will learn how chronic stress
causes health problems and how you can improve your ability to cope with
stress and fortify yourself against the negative health effects of our
stressful modern world.
Maintaining balance in today’s stressful world requires a multimodal approach that encompasses healthy eating habits, getting plenty of exercise, and using innovative natural ingredients to support the body’s natural adaptive abilities. Regular blood testing of DHEA-s, and morning and evening cortisol levels help ensure that stress hormones remain in balance.
- B-Complex vitamin:
- Thiamine (B1): 75 – 125 mg daily
- Riboflavin (B2): 50 mg daily
- Niacin (B3): 50 – 190 mg daily
- Folate (preferably as L-methylfolate): 400 – 1000 mcg daily
- Vitamin B12: 300 – 600 mcg daily
- Biotin: 300 – 3000 mcg daily
- Pantothenic acid: 100 – 600 mg daily
- Vitamin C: 1000 – 2000 mg daily
- Fish oil (with olive polyphenols): 2,000 – 4000 mg daily
- Phosphatidylserine: 100 – 600 mg daily
- L-Theanine: 200 – 400 mg daily
- Calcium: 200 – 1200 mg daily
- Magnesium: 140 – 500 elemental milligrams of highly-absorbable magnesium
- Zinc: 30 mg daily
- Chromium (Crominex™): 500 mcg daily
- Selenium: 200 mcg daily
- Manganese: 1 mg daily
- Comprehensive multivitamin formula: Per label instructions (note: some of the nutrients mentioned in the protocol [i.e. zinc, selenium, manganese, and vitamin C] can be obtained by taking a high quality multivitamin/ mineral supplement).
- Probiotics (containing a blend of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175): 3 billion CFUs daily
In addition, the following blood testing resources may be helpful:
The Fight or Flight Response
Stress generally occurs when external stimuli disturb the dynamic balance
of the body’s physiological processes.7 The stress, or “fight or
flight,” response begins in the brain, where the perception of a threat
triggers the release of corticotropin releasing hormone (CRH) from the
region called the hypothalamus. This stimulates the anterior pituitary, a
gland that sits just under the hypothalamus, to increase release of
adrenocorticotropic hormone (ACTH) into the bloodstream. ACTH then acts on
the adrenal cortex, raising production and release of cortisol and the less
active glucocorticoid, corticosterone, as well as another adrenal hormone
called dehydroepiandrosterone, or DHEA.8
The signaling network between the nervous system and adrenal glands is
called the hypothalamic-pituitary-adrenal (HPA) axis and is regulated in
part by a negative feedback mechanism, through which rising blood levels of
cortisol inhibit release of both CRH and ACTH.3,9
Stress also directly engages sympathetic nervous system signaling in the
brain region called the locus coeruleus. Catecholamine neurohormones
(epinephrine and norepinephrine, also known as adrenaline and
noradrenaline) released by the adrenal medulla and sympathetic nerve
endings have physiologic effects intended to help the body respond and
adapt to stressful circumstances. Although it tends to work in concert with
the HPA axis, the sympathetic nervous system also functions independently
to activate the stress response.3,9
As mediators of the stress response, cortisol and catecholamines have
profound effects throughout the body (see Table 1). When acutely elevated,
they help prepare the body to escape danger. For example, cardiac output
increases to support stronger blood flow; blood sugar levels increase to
meet higher energy demands; pupils dilate to allow for greater visual
input; alertness and cognition are enhanced; and digestive and reproductive
functions are inhibited due to their not being essential in the short term.9
Table 1: Hidden Causes of Acute Stress
Acute Adaptive Stress Response
Low blood glucose level10,11
Catecholamines stimulate breakdown of carbohydrate stores
and conversion of protein and fat into glucose
Cortisol inhibits glucose use by non-central nervous system
Low blood pressure3,12
Catecholamines stimulate constriction of blood vessels
Cortisol increases sodium and water retention in the
Low oxygen saturation3,13,14
Catecholamines stimulate the respiratory center of the
brain to increase breathing, increase heart rate and
contraction strength, and selectively constrict blood
Catecholamines and cortisol alter cell metabolism to
restore reductive-oxidative balance
Catecholamines and cortisol modulate immune activities
The acute stress response can lead to positive adaptive effects, but when
the HPA axis and locus coeruleus are chronically activated, their effects
become maladaptive: the response to a chronic or repeated stress may become
dull, yet, at the same time, sensitivity to new stressors may be enhanced.12,17 A dysregulated stress response results in altered patterns
of cortisol and catecholamine production and/or receptor response to them.3,9 Chronic stress may even alter brain structure.18
In addition, impairment of the HPA axis due to chronic stress appears to
suppress DHEA production and release, even under acutely stressful
circumstances.8,19 This is important because DHEA opposes some
of the actions of cortisol: it protects nerves and stimulates development
of neuronal connections, has immune-regulating effects that oppose and
balance those of cortisol, and may prevent cortisol-induced metabolic
disturbances.8 The exact nature of the response to chronic
stress depends on individual characteristics such as personality traits,
gender and age, life experiences, and genetic and epigenetic factors.3
Prolonged stress is associated with many chronic disorders and diseases
affecting all of the body’s organ systems, and as life’s stressors take
their toll on the psyche and body, chronic illness itself becomes a source
of stress. The two-way relationship between stress and disease creates a
downward spiral in mental and physical health that can become difficult to
Stress and the Circadian Rhythm
The HPA axis is closely regulated by circadian signaling in the brain. This
circadian signaling is affected by day and night (light and dark) cycles,
patterns of eating times, and most likely other factors yet to be
discovered. Normally, cortisol levels peak shortly after waking in the
morning and are lowest around bedtime. By acting on receptors throughout
the body, cortisol imposes diurnal (two-phase; day-night) rhythms to other
Numerous studies have shown that disruption of the circadian clock, such as
due to shift work, sleep apnea, and other sleep disorders, is associated
with health problems including cardiovascular disease, type 2 diabetes,
obesity, and an array of age-related diseases.26,27 Circadian
disturbances may even correlate with reduced lifespan.28 Chronic
stress appears to impair circadian control of the HPA axis, which can
result in either excess evening levels or blunted morning levels of
cortisol.29 These dysfunctional patterns of cortisol release may
be an underlying factor in the negative physical and mental health
consequences of chronic stress and circadian rhythm disruption.30
Stress and Inflammation
One important way that chronic stress affects long-term health is through
dysregulated inflammatory signaling. Although cortisol is best known for
its immunosuppressive action, its effects on immunity are complex,
stimulating some aspects of immunity and inhibiting others.1,25
A phenomenon known as glucocorticoid resistance, in which tissues and cells
become less responsive to cortisol, occurs following long-term elevation of
cortisol levels due to chronic stress.31,32
Chronic stress-induced immune dysfunction results in reduced immune
protection against infections and cancer, as well as inflammatory
conditions, such as allergic and autoimmune disorders, and conditions
related to low-level systemic inflammation like heart disease and diabetes.1,33 Once inflammation is initiated, it perpetuates the stress
response through the actions of cytokines (small signaling proteins of the
immune system) on the hypothalamus, pituitary, and adrenal cortex.25,34
Stress and the Microbiome
Chronic stress may impact health through interactions with the gut
microbiome—the trillions of microorganisms that reside in the intestines.
Through its relationship with nervous system signaling, often referred to
as the “gut-microbiota-brain axis,” and its ability to regulate the immune
system, a healthy microbiome appears to be essential for modulating stress
responsiveness and preventing overstimulation of the HPA axis. Conditions
associated with chronic stress have been shown to alter the composition of
the gut microbial community. Microbial imbalances, in turn, can cause
intestinal and systemic inflammation and abnormal neurological signaling
that can trigger HPA activation.35-38
The Epigenetics of Stress
Exposure to stress early in life can alter stress responsiveness and
resilience throughout life. Part of this is likely due to effects of stress
on brain and adrenal gland development; another important element is
epigenetics. Epigenetics refers to environmentally induced modifications to
gene expression patterns (as opposed to changes in gene sequence) or
factors that control how genes are used to direct protein synthesis in
cells. These modifications are lasting, but can be reversed by future
The epigenetic changes induced by prenatal and early life stress result in
hyperresponsiveness of the HPA axis and increased risk of neuropsychiatric
problems in adulthood, such as depression, anxiety, and post-traumatic
stress disorder.39-41 Emerging research has shown that
stress-induced epigenetic changes can also occur in adulthood, affecting
HPA axis responsiveness and increasing vulnerability to stress-related
health problems.42 In addition, because the epigenome is passed
on to offspring by both parents, exposure to intense or unremitting stress
has implications for resilience and health that may span multiple
Chronic stress can exert considerable body-wide health effects. It can
contribute to the onset or worsening of many types of ailments. The
following discussion highlights some of the more common conditions to which
chronic stress often contributes.
One of the most widely recognized health effects of chronic stress is
heart disease. Through the effects of cortisol and catecholamines, and by disrupting
circadian rhythms through sleep disturbance, chronic stress has been shown
to impair nervous system regulation of cardiac function,49 and
can cause high blood pressure, arrhythmia, and vascular inflammation
leading to atherosclerosis and blood clots.50 Prolonged stress
at home and at work has been clearly linked to increased risk of coronary
artery disease and cardiac events including heart attack and stroke.12,51 A recent meta-analysis highlights the influence of work
stress on heart disease risk: after analyzing data from more than 740,000
men and women, researchers found that people who work 55 or more hours per
week have a 12% increased risk of coronary artery disease and a 21%
increased risk of stroke compared with those who work less.52
Acute stress can also pose a threat to the heart. Studies have noted the
incidence of heart attack increases following acutely stressful events such
as earthquakes and World Cup soccer championships.53 Takotsubo
cardiomyopathy, a sudden weakening of the heart muscle that mimics the
symptoms of heart attack or angina and is potentially fatal, is another
example of the danger of acute stress to the heart. Also known as stress
cardiomyopathy, broken heart syndrome, and apical ballooning syndrome,
Takotsubo cardiomyopathy typically occurs a few hours after a severe
physical or emotional trauma and is most common in postmenopausal women.54,55
Persistently high cortisol levels, a marker of chronic stress, can trigger
changes to neuronal structure and reduce brain plasticity (the ability to
make new neuronal connections).56 Chronic stress is closely
associated with several common neuropsychiatric disorders, including
anxiety, dementia, and
Inflammation in the brain triggered by stress-related signaling appears to
underlie a number of these illnesses.57 In Alzheimer disease,
stress-related immune dysfunction appears to weaken the brain’s ability to
clear amyloid-beta, a protein involved in Alzheimer disease development and
progression.58,59 Early life, repetitive, or chronic stress may
also reduce the activity of nerve growth factors, especially brain-derived
neurotrophic factor (BDNF), involved in formation of new nerve connections.60-62 Low levels of BDNF are associated with mood disorders as
well as learning and memory deficits.62 Furthermore, these
stress-related changes may be encoded epigenetically, altering nerve system
plasticity and function in lasting ways.63
A growing body of evidence suggests that the neurohormones of the stress
response can promote the initiation and progression of cancer.64,65 Furthermore, chronic stress may be associated with
behaviors, such as smoking, substance abuse, overeating, and decreased
physical activity, that increase the risks of certain cancers.66,67 Coping with a cancer diagnosis, symptoms, and treatment is
inherently extremely stressful for some individuals,68,69 yet a
high burden of stress may negatively impact response to cancer treatment
The mechanism by which stress influences cancer is likely to be
multifaceted, but the cornerstone may be immune dysregulation, marked by
decreased immune surveillance and systemic inflammation. HPA axis
dysregulation suppresses immune defenses against cancer, and chronic
systemic inflammation creates conditions that support cancer initiation,
progression, and metastasis.72,73 Inflammation may stem from
other stress-induced sequelae, including weight gain and metabolic
disturbance, disruption of the gut microbiome, and epigenetic alterations72; in turn, inflammation can contribute to these processes.74 In addition, stress may affect cancer development by
desynchronizing circadian regulation of biological activities.29,75
Metabolic Disturbance: Why Does Stress Make it Hard to Lose Weight?
One of the most important functions of the stress response is to ensure
that adequate energy is available to cope with stressful circumstances.
During episodes of acute stress, appetite is suppressed to reserve
attention for fight or flight, and extra energy in the form of glucose is
freed from stored fats and carbohydrates. Under conditions of chronic
stress, however, appetite is typically up-regulated and cravings for
high-sugar, high-fat, high-calorie foods can intensify as a result of
long-term hyperstimulation of the HPA axis and its complex interactions
with appetite-regulating neurohormones such as ghrelin and leptin. For
reasons that are not entirely clear, an increased appetite as a reaction to
chronic stress is more pronounced in women than men.10,76
To make matters worse, chronic stress and HPA axis dysregulation are
associated with insulin resistance and
type 2 diabetes
, as well as fat tissue growth and obesity.77,78 In one study,
salivary cortisol tests showed disturbances in the diurnal rhythm of
cortisol release were correlated with body mass index (BMI) and waist
circumference, a measure of visceral fat and one of the cardiovascular risk
factors in metabolic syndrome.79 These metabolic consequences of
long-term stress then promote widespread inflammatory signaling that
damages blood vessels and increases cardiovascular risk.80,81
Systemic inflammation also affects the nervous system, contributing to mood
and cognitive disorders, and creates a vicious cycle of increased HPA axis
Although widely believed that chronic stress can lead to weakened thyroid
function, there is little evidence as of the date of this writing to
support this notion. In one study, hair cortisol levels were higher in
adults with overt hypothyroidism than in healthy adults, and were
correlated with higher body weight and BMI; however, in participants with
subclinical hypothyroidism, a condition characterized by normal to slightly
abnormal lab values and possibly symptoms of hypothyroidism, hair cortisol
levels were not significantly different from those of healthy participants.83 Findings from preliminary studies indicate stress may
contribute to the onset of autoimmune hypothyroidism; however, a review of
these studies was unable to confirm the connection.84 On the
other hand, evidence from animal studies suggest hypothyroidism may trigger
HPA axis dysregulation and, when chronic, reduce adrenal output.85,86
Additional Health Conditions Stress Can Worsen
Virtually any health condition can be negatively affected by stress. In
addition to those already discussed, the following are some of the
disorders and diseases that stress may impact:
Chronic fatigue syndrome90
Upper and lower respiratory infections91
Irritable bowel syndrome93
Although the effects of chronic stress can vary among individuals, several
laboratory and clinical assessments can help determine if stress may be
contributing to health problems. Objective tests that may be helpful in
assessing the extent to which stress is affecting overall health include
cortisol, DHEA level, salivary alpha-[a] amylase and immunoglobulin A (IgA)
levels, and heart rate variability.
Measuring cortisol levels can be helpful in assessing HPA axis function.
Cortisol levels in saliva, blood, urine, and hair have been shown to be
reliable markers of adrenal cortisol output.98,99 These tests
are widely available and are sometimes used as indicators of HPA axis
function. In general, long-term increased cortisol output, reflecting
over-activity of the HPA axis, is typical in major depression, while
decreased cortisol output, reflecting under-activity of the HPA axis, is
typical in chronic fatigue syndrome and post-traumatic stress disorder.100
is a non-invasive test that may be helpful in determining whether the
circadian rhythm of adrenal gland function is intact or disturbed. Late
night salivary cortisol is sometimes used to diagnose Cushing syndrome
(a condition caused by excess exposure to cortisol or drugs that mimic
cortisol), but tests that measure cortisol levels at multiple times in
a day, creating a curve that reflects the diurnal pattern of cortisol
release, may have broader usefulness in assessing stress.101,102 One research review found that flatter diurnal
cortisol curves are correlated with poorer health.103
Cortisol levels rise gradually with age and are affected by gender,
especially around puberty and in the elderly. Although every lab determines
its own reference ranges, peak salivary cortisol levels (within the first
hour after waking) in adults appear to range from 1.8 to 26 nanomoles per
liter (nmol/L), and evening trough levels (about 16 hours after waking)
range from 0.2 to 3.5 nmol/L.104
concentration is a novel and non-invasive method of evaluating
long-term cortisol exposure over months to years. Because stress levels
can fluctuate over time, cortisol is generally measured in the three
centimeters of hair closest to the scalp (reflecting HPA axis activity
during the previous three months).105 Cortisol
concentrations in scalp hair have been found to vary with psychological
and physical stressors, and have been correlated with perceived stress
and stress-related symptoms and illnesses, including obesity, metabolic
syndrome, and cardiovascular disease.99,106
Salivary Alpha [a]-Amylase and Immunoglobulin A (IgA)
a-amylase is a starch-digesting enzyme produced in the salivary glands as
well as the pancreas. Production of salivary a-amylase increases under
stimulation by the sympathetic nervous system, which triggers the “fight or
flight” reaction and has a critical role in the stress response. On the
other hand, production of salivary proteins like a-amylase and the antibody
IgA is inhibited by the parasympathetic nervous system, which controls
resting body functions. Therefore, salivary a-amylase and salivary IgA have
been proposed as markers of the balance of nervous system regulation and
objective measures of stress.107-109
Numerous studies show that a-amylase increases as a result of physical and
psychological stress, and high levels have been seen in stress-related
conditions such as anxiety.107,110 It is sometimes tested along
with salivary cortisol, which reflects HPA axis activity, to provide a more
comprehensive assessment of stress. Although not performed routinely,
evidence suggests this combination of salivary tests may be useful for
non-invasively and objectively evaluating the contribution of stress in
patients with chronic conditions111 and monitoring the effects
of stress-reducing therapies.112
Salivary secretory IgA (sIgA) has also been proposed as a marker of stress.
A number of studies have shown that acute stress can increase levels of
this important antibody.113-115 With chronic stress, however,
sIgA appears to be depleted and salivary levels drop,116,117
possibly increasing risk of oral, gastrointestinal, and respiratory
infections.118 Interpretation of salivary sIgA is somewhat
challenging due to its sensitivity to other factors in the oral
Salivary sIgA and a-amylase tests are commercially available and frequently
recommended and interpreted by integrative health care providers. In
general, standardization of these salivary tests and more information about
factors that interfere with their interpretation, such as smoking, food and
beverage consumption, and medication use, will help increase their
usefulness and acceptance.108,119,120
Dehydroepiandrosterone (DHEA) is an adrenal hormone that opposes some of
the actions of cortisol in many tissues. Acute stress can increase
production of both DHEA and cortisol in healthy individuals, but chronic
stress has been correlated with low DHEA and high cortisol output.8 In one study, levels of DHEA-S (DHEA-Sulfate, the form of DHEA
typically measured in the blood) were 23% lower in healthy adults with the
highest perceived work-related stress compared to those with the lowest
work-related stress.121 The balance between cortisol and DHEA
production also varies dramatically with age: DHEA release is lowest in
older age, and it is thought that the unabated action of cortisol in the
presence of declining amounts of DHEA may contribute to age- and
Evidence suggests blood levels of DHEA-S that generally correspond with
optimal health are 350–500 µg/dL for men and 275–400 µg/dL for women.
Measuring the ratio of serum cortisol to DHEA-S may also provide some
insights into the function of the adrenal gland and stress resilience.8
Heart Rate Variability
The heartbeat is not a precisely regular rhythm but instead oscillates
unpredictably over time in response to dynamic shifting in the balance of
sympathetic and parasympathetic regulation. Heart rate variability is the
fluctuation in the length of time between heartbeats.124 In a
healthy person at rest, when the parasympathetic nervous system is the
predominant heart rhythm regulator, heart rate variability increases, but
during times of stress, when the sympathetic nervous system is strongly
activated, heart rate variability decreases. Like salivary a-amylase, heart
rate variability at rest provides information regarding the stress-related
activity of the nervous system.125 Greater variability in the
heart rate reflects more robust ability to adapt to changing conditions.124
A growing body of evidence shows that resting heart rate variability is a
meaningful reflection of cardiac and nervous system activity.124,125 Low heart rate variability has been noted to be closely
correlated with other measures of stress and is an indicator of low
stress-resilience and increased risk of heart attack and overall mortality.125-128 Furthermore, stress management strategies like exercise
and mindfulness practices can improve heart rate variability.128,129 Taken together, the evidence suggests heart rate
variability may prove helpful in predicting risk of stress-related physical
and psychological disorders.126,130
Heart rate variability is measured during long (24-hour), short
(five-minute), or ultrashort (shorter than five-minute) monitoring periods.
At this time, 24-hour data sets are considered the “gold standard” and seem
to offer a better reflection of health status. Questions
remain about the significance of short- and ultrashort-term heart rate
variability measurements, ideal timing of data collection, frequency of
oscillations, and the influence of individual factors such as gender,
disease status, and medication use on heart rate variability measurements.124 Nevertheless, devices that measure heart rate variability
are increasingly commercially available.
Stress is well known to trigger changes in eating behaviors, often
increasing appetite for unhealthy “comfort” foods like those high in sugar
and fat.212 One reason may be that stress alters levels of
appetite-regulating hormones, ghrelin and leptin, producing more hunger
signaling.213 Although not everyone eats more in response to
stress (about 40% of individuals eat more, 40% eat less, and 20% eat the
same number of calories when under stress), a stress-induced rise in
preference for high-sugar foods has been consistently observed and may be
partly due to a dampening effect of sugar on the stress response.214-217 Compounding the problem, stress appears to increase
susceptibility to diet-related metabolic disturbances like abdominal
obesity and insulin resistance.218
Countering stress-related appetite changes and food cravings is
challenging; however, eating a healthy diet may be even more important
during times of stress. Healthy eating habits can help ensure adequate
intake of vitamins, minerals, protein, complex carbohydrates,
anti-inflammatory fats, fiber, and phytochemicals needed to combat the
negative health effects of chronic stress and interrupt the cycle of stress
and stress-related behaviors.219,220
Eat More Fruits and Vegetables
Increasing fruit and vegetable intake can help combat stress. A study in
young adults showed that increasing fruit and vegetable intake by two
servings per day for two weeks resulted in enhanced psychological
well-being, vitality, flourishing, and motivation.221 A
Mediterranean-style diet, which emphasizes olive oil, whole grains, fruits,
vegetables, fish, and nuts and seeds, may improve the stress response and
has been associated with better regulation of HPA axis activity. This
dietary pattern may also mitigate the effects of stress by reducing
systemic inflammation and the risk of many chronic health problems.222-224
Eat Breakfast Regularly
Eating breakfast may help build stress resilience. Compared to breakfast
skipping, habitual breakfast eating was associated with lower levels of
perceived stress, better cognitive function, and fewer job injuries and
accidents in a study that included more than 800 nurses.225 In
another study in 65 female participants, habitual breakfast skippers had
blunted diurnal cortisol variation, increased overall cortisol output, and
higher blood pressure compared with habitual breakfast eaters, suggesting a
morning meal may be important for maintaining normal circadian regulation
of the HPA axis.226
Minimize Caffeine and Alcohol Intake
Caffeine may seem attractive to those affected by stress-related fatigue,
but its effects may aggravate symptoms such as anxiety and poor sleep in
susceptible people.227,228 Caffeine stimulates the sympathetic
nervous system, and in this way may activate the stress response.229 Even with daily consumption, its intake can raise cortisol
levels and has been found to increase the cortisol response to mental
stress230,231 and prolong the effects of physical stress on
heart rate and blood pressure.232 In one study, habitual coffee
drinking was associated with greater increases in heart rate and vascular
inflammation in response to mental stress.233 On the other hand,
drinking coffee appears to promote healthy metabolism and may protect
against type 2 diabetes, liver cancer, and cognitive decline.234
While sensitive individuals may fare better eliminating caffeine during
times of stress, moderate intake may be reasonable for others.227
Alcohol is often used as a relaxant during times of stress235,236; however, excessive intake raises cortisol levels and
long-term use leads to dysregulated HPA axis signaling and disrupts the
normal function of the stress response.237-239 Individuals
experiencing stress-related insomnia frequently turn to alcohol as a form
of self-medication, but because alcohol erodes sleep quality and quantity,
it may actually exacerbate sleep difficulties.240 In addition,
because people experiencing intense life stress or with a history of early
life stress are more vulnerable to developing problematic drinking habits,239,241 it is especially important to avoid stress-related
A variety of natural, integrative interventions have been shown to help
balance HPA axis function and counteract the detrimental effects of chronic
Multivitamins and B-Complex Vitamins
Deficiencies of B vitamins are associated with neuropsychiatric disorders
such as depression, Alzheimer disease, schizophrenia, and other types of
psychosis and dementia, and adequate amounts of all B vitamins are needed
for healthy nervous system function.242,243
The ability of multivitamins to reduce perceived stress and fatigue has
been demonstrated in a number of trials.244-248 In one
randomized controlled trial in 60 working adults, those receiving a
high-dose B complex daily for 12 weeks reported lower levels of stress,
confusion, and depressed mood compared with those receiving placebo.249 A review of the research concluded that multivitamins, and B
complex supplements in particular, can be effective for lowering perceived
stress, reducing mild psychiatric symptoms, and improving everyday mood in
B vitamins may also support normal HPA axis function. In a
placebo-controlled trial with 138 subjects, 16 weeks of supplementation
with a multivitamin containing B vitamins increased the cortisol awakening
response. The cortisol awakening response, which occurs about 30 minutes
after waking and generally results in the highest cortisol level of the
day, is considered a marker of healthy HPA axis tone and has been
associated with lower distress levels during the rest of the day.251 Another randomized controlled crossover trial examined the
effect of one week of treatment with a multivitamin supplement in 240
Chinese military personnel who underwent intense physical stress. The
multivitamin was associated with better recovery of normal HPA axis
function and improvements in psychological symptoms.252
Vitamin C (Ascorbic Acid)
The adrenal glands have the highest concentration of vitamin C in the body.253 In addition to its well-known function as a free radical
scavenger, vitamin C is a cofactor in the synthesis of
catecholamines—neurohormones involved in the stress response—and may help
modulate central nervous system activities.253-255 Levels of
vitamin C in the blood and white blood cells drop quickly during times of
stress or infection,256 and symptoms of depression and anxiety
have been correlated with low intake and low circulating levels of vitamin
In a controlled clinical trial, patients with stress-induced anxiety and
depression had lower levels of vitamin C, as well as vitamins E and A, than
healthy subjects, and the addition of these nutrients (1,000 mg per day
vitamin C, 800 mg per day vitamin E, and 600 mg per day vitamin A) to
antidepressant therapy led to greater reductions in symptoms of anxiety and
depression compared with antidepressant therapy alone.257
Another controlled trial found that supplementing with 500 mg per day of
vitamin C reduced anxiety levels and lowered average heart rate in healthy
high school students.258 In addition, a review of research
indicated high doses of vitamin C may reduce anxiety and mitigate
stress-related increases in blood pressure.259
Omega-3 Fatty Acids
Omega-3 fatty acids (primarily EPA [eicosapentaenoic acid] and DHA
[docosahexaenoic acid] from fish oil) may help prevent and treat stress,
anxiety, and depression.260-262 Low blood levels of EPA and DHA
have been correlated with several biological indicators of stress: elevated
markers of inflammation, dysregulated nervous system signaling, and HPA
axis hyper-reactivity.263,264 Conversely, omega-6 fatty acids,
mainly obtained through eating animal fats and processed vegetable oils,
promote inflammation and can thereby induce stress signaling and contribute
to stress-related illnesses.261
In a randomized controlled trial in participants with high triglyceride
levels, taking 3,400 mg of combined EPA and DHA for eight weeks increased
heart rate variability, indicating lower stress-related nervous system
signaling; however, a lower dose of 850 mg per day had no effect.265 Another controlled trial found that three weeks of treatment
with 60 mg EPA and 252 mg DHA per day improved perceived stress and anxiety
and reduced cortisol levels in alcoholic subjects in a residential
treatment program.266 Evidence from trials in patients with
depression suggest omega-3 fatty acids can correct HPA hyperactivity,
mitigate symptoms, and may improve responsiveness to antidepressant
L-theanine is an amino acid found in tea that has demonstrated anti-stress
effects. Numerous studies have found that tea and theanine reduce perceived
stress and physiologic markers of the stress response, including blood
pressure, heart rate, cortisol levels, and patterns of brain activity.268 In one trial that included 20 pharmacy students, taking 200
mg theanine twice daily for one week decreased morning salivary a-amylase
levels more than placebo.269 Its short-term effect was confirmed
in another randomized controlled trial in 36 healthy participants between
18 and 40 years old: a single 200 mg dose of theanine decreased subjective
stress one hour after administration and the cortisol response to a
cognitive stressor three hours after administration. In addition, in a
subset of participants whose scores on a test of tendency to experience
anxiety were high, theanine increased brain wave activity associated with
relaxation.270 Theanine has also been shown to counter the
stress-inducing effects of caffeine and enhance focused attention,271 and a two-month clinical trial noted that theanine, in
combination with a vitamin/mineral/herbal supplement, lowered perceived
stress scores and improved cognitive function in elderly subjects.272
The phospholipid phosphatidylserine is found in cell membranes and helps
facilitate healthy cellular communication. It modulates the tissue response
to inflammation and can reduce oxidative stress.273 Several
studies have shown that phosphatidylserine can balance HPA axis signaling
and may limit the negative consequences of over-activation of the adrenal
In a trial in 75 healthy male volunteers, taking a supplement providing 400
mg each of phosphatidylserine and its precursor phosphatidic acid for 42
days diminished the HPA axis response to acute stress in a subset of men
reporting high levels of chronic stress.274 In other clinical
research, this same combination was noted to dampen the stress response to
mental stress,275 and 300 mg per day of phosphatidylserine alone
reduced perceived stress and improved mood in healthy young adults prone to
negative emotions like anxiety, worry, and fear.276
Phosphatidylserine has also been found to lower cortisol levels overall and
reduce the cortisol response to acute exercise in men, an effect that may
help to prevent the harmful outcomes of overtraining, such as decreased
performance, injury, immune suppression, and deterioration of psychological
L-tryptophan is an amino acid precursor to the neurotransmitter serotonin.
Serotonin has a complex relationship with the stress response.278 Stress-induced inflammation appears to cause excessive
breakdown of tryptophan, which may decrease serotonin production and
increase risk of depression279; in addition, tryptophan
depletion has been shown to increase stress sensitivity.280
Studies in healthy adults suggest tryptophan supplementation, ranging from
800 to 2,800 mg per day, may reduce the cortisol response to stress,
mitigate stress-related negative moods, and prevent stress eating in some
individuals.281-283 In a randomized controlled trial, a
tryptophan-rich hydrolyzed protein supplement increased positive mood and
lowered cortisol release in response to acute stress.284
Bioactive Milk Peptides
Upon ingestion, milk proteins are broken down into peptides (shortened
amino acid chains) by enzymes. Some of the resulting peptides can be
absorbed intact and exert biological activities.285 For example,
a-lactalbumin is a bioactive milk peptide that has a high tryptophan
content and has been found to support healthy neurological function,
improve mood, and promote sleep.286 An enzyme-treated form of
the milk protein, casein, has also demonstrated anti-stress and relaxing
properties in animal studies, and appears to work by increasing signaling
via receptors for GABA—a neurotransmitter that generally inhibits nervous
One randomized, controlled, crossover trial included 63 women with
stress-related symptoms such as anxiety, sleep problems, and fatigue.
Thirty days of treatment with 150 mg per day of a-S1 casein hydrolysate (a
form of bioactive milk peptides) was more effective than placebo at
relieving symptoms.290 In healthy volunteers, a 200 mg dose of
a-S1 casein hydrolysate was found to mitigate increases in blood pressure,
heart rate, and cortisol release induced by experimental stress.291
Probiotics and Prebiotics
The gut microbiome, nervous system, and HPA axis are closely connected.
Probiotics and prebiotics (indigestible dietary carbohydrates that support
the growth of beneficial bacterial colonies) can improve the balance of gut
bacteria, and a growing body of evidence points to their potential to have
a positive impact on the stress response.35,37,260 Research
indicating probiotics may lower stress reactivity and anxiety, and improve
mood, memory, and cognition have led some researchers to call probiotics
with these effects psychobiotics.292
Fermented milk products made with Lactobacillus casei strain
Shirota have been found in several trials to suppress cortisol elevations
in response to stress and reduce stress-related health concerns such as
depressed or anxious mood, digestive upset, and cold symptoms in healthy
medical students.293-295 In a randomized controlled trial, 10
days of supplementation with 10 billion colony forming units (CFUs) of L. plantarum 299v per day decreased salivary cortisol levels in
students facing an upcoming exam.296 In other controlled trials,
taking a combination of L. helveticus R0052 and Bifidobacterium longum R0175, at a dose of 3 billion CFUs per day,
for 30 days lowered scores on scales of perceived stress as well as urinary
cortisol levels in healthy volunteers,297 and supplementing with
1 billion CFUs per day of B. longum 1714 for four weeks suppressed
the cortisol rise and subjective anxiety associated with an acute stressor.298
Prebiotics are also demonstrating positive effects in clinical research: in
a trial in 45 healthy adults, taking 5.5 grams of a prebiotic supplement
containing galacto-oligosaccharides for three weeks resulted in lower
early-morning cortisol levels and more balanced processing of positive and
negative emotional stimuli.299
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 plays a central role in circadian regulation of
body systems, including the HPA axis.300 Stress can reduce
melatonin levels and destabilize the body’s biological rhythms.301 Chronic disruption of the brain’s internal clock, such as
through shift-work or insomnia, harms mental and physical health.302,303
Melatonin supplementation can improve sleep quantity and quality and help
restore normal circadian processes,304,305 which may lead to
reduced stress and prevention of stress-related deterioration of health.306 In one study, 2 mg of melatonin taken in the evening for six
months improved sleep and increased DHEA-S levels in a group of elderly
DHEA is an adrenal hormone that, like cortisol, is secreted in response to
acute stress, but chronic stress has been associated with low levels.8 The effect of stress on DHEA may be one of the factors linking
stress to poor health and accelerated aging.121 Low DHEA-S
levels have been correlated with conditions such as osteoporosis, cognitive
decline and dementia, cardiovascular disease, mood disorders, and sexual
dysfunction.123 Findings from preclinical and clinical research
suggest DHEA replacement therapy may have a role in protecting aging bone
and vasculature and may help in the treatment of depression and sexual
In a randomized, placebo-controlled, crossover trial that enrolled 13 men
and 17 women between ages 40 and 70 years, treatment with 50 mg DHEA daily
for six months led to significant improvements in physical and
psychological well-being. Subjects in this study reported a better ability
to handle stress, improved mood, and being generally relaxed.308
In a different study, 24 healthy young men took high-dose DHEA (150 mg
twice daily) for seven days. Subjects reported improved mood, and DHEA
treatment led to reduced levels of cortisol on evening measures.309
Supplemental doses of DHEA typically range from 10–25 mg daily for women and 25–75 mg daily for men, but should be based on DHEA-S blood levels. More information is available in Life Extension’s
DHEA Restoration Therapy protocol.
Adaptogenic herbs have multi-faceted beneficial effects that support the
body’s intrinsic resilience to stressful conditions. They work by
regulating biological networks in ways that support homeostasis. For
example, adaptogens can raise energy levels, yet also support sound sleep.
Some typical reasons adaptogens are used include to relieve fatigue,
improve cognitive function and mood, and support the immune system.310-312
Magnolia and phellodendron.
Magnolia (Magnolia officinalis) is an important plant in
traditional Chinese herbal medicine. Its active constituents, magnolol and
honokiol, have been found in preclinical and clinical trials to have a
variety of beneficial effects, including stress reduction.313 In
rodents exposed to chronic stress, both magnolol and honokiol, as well as
their combination, have been found to normalize serotonin and HPA axis
activity, increase levels of a brain growth factor (brain-derived
neurotrophic factor, or BDNF), reduce neuroinflammation and brain oxidative
stress, and prevent behaviors indicative of depression.314-317
A combination of magnolia and phellodendron ( Phellodendron amurense) has also been studied for anti-stress
effects. In one controlled clinical trial, 56 healthy subjects with
moderate stress levels received either a supplement providing 250 mg of
magnolia plus phellodendron or placebo twice daily for four weeks.
Participants underwent three (morning, noon, and night) salivary cortisol
tests and answered mood questionnaires at the beginning and end of the
trial. Those receiving the supplement had lower total cortisol exposure and
better mood scores than those receiving placebo.318
The same combination supplement was studied for its effect on
stress-induced appetite and weight gain. In one controlled trial, magnolia
plus phellodendron, at a dose of 250 mg three times daily for six weeks,
reduced weight gain compared with placebo in overweight but otherwise
healthy premenopausal women who reported stress eating and above-average
levels of anxiety.319 In another similarly designed trial,
magnolia plus phellodendron reduced temporary anxiety, but did not affect
longstanding depression or anxiety, appetite, sleep, or levels of salivary
cortisol and amylase.320
Holy basil (Ocimum sanctum, also known as tulsi basil) is an
adaptogenic herb from the Ayurvedic tradition. In Hindu spirituality, holy
basil is considered a sacred plant and an incarnation of the goddess,
Tulsi.321 A number of clinical and preclinical studies have
demonstrated holy basil’s anti-stress potential by providing evidence that
it improves mood and cognition, normalizes metabolism, regulates immune
function, reduces oxidative stress, and prevents toxic damage in various
tissues by supporting detoxification.321,322
In a randomized controlled trial with 40 participants, 300 mg of holy basil
extract per day for 30 days resulted in reduced anxiety symptoms and
improved cognitive test scores compared with placebo.323
Findings from another randomized controlled trial, in which 150
participants received 1,200 mg holy basil per day or placebo, indicated
that holy basil lowered stress-related symptoms such as anxiety, fatigue,
sleep difficulties, and sexual dysfunction.324 A pilot trial in
which 35 patients with anxiety were treated with 500 mg holy basil twice
daily found that treatment led to reductions in symptoms of anxiety,
stress, and depression.325
Ashwagandha (Withania somnifera) is another important herb in the
Ayurvedic herbal pharmacy, in which it is used as a general tonic and
aphrodisiac.326 Numerous preclinical studies show ashwagandha
prevents oxidative damage, supports normal mitochondrial activity,
modulates central nervous system signaling, and contributes to immune
regulation, suggesting it may be useful in the treatment of chronic
stress-related, inflammatory, metabolic, cardiovascular, and
Several clinical trials further indicate that ashwagandha is effective for
relieving stress and anxiety.330 For example, in a trial with 64
participants, 300 mg ashwagandha extract twice daily was more effective for
reducing perceived stress scores and lowering blood cortisol levels than
placebo after 60 days of treatment.331 Another trial noted the
possible beneficial effects of ashwagandha on weight management in people
with chronic stress. Fifty-two chronically stressed participants received
either 300 mg ashwagandha twice daily or placebo for eight weeks; those
receiving ashwagandha had greater reductions in perceived stress and serum
cortisol levels, more improvements in food cravings and eating behaviors,
and greater weight loss than those receiving placebo.332
Bacopa (Bacopa monnieri) has been used historically in Ayurvedic
medicine to support healthy cognitive function.333 A number of
animal studies have demonstrated its adaptogenic potential, noting its
ability to normalize stress hormone levels and neurotransmitter balance,334 reduce oxidative stress,335 protect against
neurodegeneration,336 and prevent or reverse other negative
physiologic and behavioral consequences of stress.337-339
Furthermore, in rodent models of chronic stress, bacopa and an active
constituent (bacopaside-I) have been found to reduce depressive behavior,
normalize HPA axis function, reduce brain oxidative stress, and prevent a
drop in BDNF and other changes in the brain environment,340-342
Bacopa has also been found to increase stress resilience and lifespan in
another laboratory animal model.343
In a preliminary trial in 17 healthy adults, a standardized extract of
bacopa, taken in single doses of 320 mg and 640 mg, improved cognitive
performance one to two hours later on multitasking mental tests while also
reducing cortisol levels, suggesting that part of its cognitive benefits
may be related to stress-reducing effects.344 In a randomized
controlled trial in 54 elderly subjects, taking 300 mg per day of bacopa
for 12 weeks led to improved cognitive performance, lower depression and
anxiety scores, and reduced heart rate compared with placebo.345
Lemon balm (Melissa officinalis) is a plant in the mint family
used in herbal medicine as a relaxing and uplifting nervous system tonic.346,347 Consumed in food or drink, lemon balm was found to
generally improve mood and cognitive performance in healthy young adults.348 In healthy subjects exposed to experimental stress,
individual doses of lemon balm had acute anti-stress and
cognitive-enhancing effects, and increased self-reported calmness and
In a pilot trial in 20 stressed volunteers with mild-to-moderate anxiety
and insomnia, 15 days of treatment with 300 mg lemon balm extract twice
daily led to symptom improvement in 19 (95%) of the participants. In
addition, 14 participants had a complete remission of anxiety, 17 had
remission of insomnia, and 14 had remission of both anxiety and insomnia.350 In a placebo-controlled clinical trial in 80 patients with
stable angina, 3 grams per day of lemon balm for eight weeks reduced
anxiety, depression, and stress, and improved sleep.351 In
animal research, lemon balm decreased stress-induced symptoms of irritable
Saffron (Crocus sativus) is a yellow spice prized for its color
and flavor. It also has a long history of use in herbal medicine for its
sedative, adaptogenic, and other properties. Several clinical trials have
shown that saffron is helpful in treating mild-to-moderate depression.353,354 Saffron and its active constituent crocin have also
demonstrated anti-stress and anti-anxiety effects in animal studies, and
preclinical evidence suggests it may exert its benefits in part by
moderating HPA axis responsiveness.355-358 In addition,
crocetin, another active compound from saffron, was found to prevent
stress-induced depressive behavior in rats.359
In a randomized controlled trial, subjects without depression but reporting
low mood who received treatment with 28 mg per day of saffron extract for
four weeks had greater improvement in mood and reductions in symptoms of
stress and anxiety than those receiving placebo.360
Ginseng is a common name for a group of similar plants, including Asian
ginseng (Panax ginseng), American ginseng (Panax quinquefolius), and Chinese ginseng ( Panax notoginseng). These plants all contain active compounds
called ginsenosides. Panax ginseng and its unique ginsenosides
have been especially widely studied for their effects on disease prevention
and overall well-being.361 This herb has been used for thousands
of years to enhance vitality and longevity, and numerous studies show it
has a broad range of actions such as immune-modulating, anti-inflammatory,
anti-cancer, free radical scavenging, neuroprotective, and
cardioprotective.362-365 With regard to stress physiology, a
fermented ginseng extract was found to reduce oxidative stress and HPA axis
signaling in response to exercise stress.366
Although unrelated to the Panax species of ginseng, Siberian
ginseng (Eleutherococcus or Acanthopanax senticosus) is
another popular adaptogenic herb. It contains active compounds called
eleutherosides and has also demonstrated a range of anti-stress properties.367
Rhodiola (Rhodiola rosea, also known as roseroot or golden root),
is an adaptogenic herb that grows in Arctic regions and is used around the
world to enhance physical and mental stamina and relieve stress.368 Rhodiola appears to modulate HPA axis function, reduce
oxidative stress, and regulate immune activity.369,370
Pilot trials in patients with chronic fatigue symptoms, burnout, and mild
anxiety have found that 400 mg rhodiola extract daily is associated with
improvements in measures of energy level, mood, sleep, cognitive function,
and general well-being.371-373 Rhodiola has also been found to
help patients with stress-induced depression.374 This effect may
be due in part to its promotion of new connections in the brain.375
Amla (Phyllanthus emblica), an adaptogen also known as Indian
gooseberry, is used in Ayurvedic medicine to restore strength and good
health.376 Some of its active constituents have demonstrated
strong oxidative stress-reducing capacity.377 In a preliminary
trial in 12 healthy volunteers, 500 mg of a standardized alma extract twice
daily for 14 days mitigated acute stress-induced increase in arterial
stiffness and decrease in cardiac blood flow.378 Research in
animals suggests alma may reduce brain oxidative stress, prevent chronic
stress-related damage to testicular tissue, improve stress resilience in
general, and lengthen lifespan.379-381
Schisandra (Schisandra chinensis) has been used for centuries in
the treatment of depression, anxiety, and insomnia, as well as a wide range
of health problems related to fatigue and weakness.382,383
Schisandra and its active constituents have also demonstrated
liver-protecting, anti-inflammatory, immunomodulating, anti-proliferative,
and cognitive enhancing effects. Schisandra also holds promise as a cardiac
and neurological protectant.382-384 Findings from animal
research suggest Schisandra may help regulate HPA axis activity and relieve
the negative effects of stress.385-387
Cordyceps (Ophiocordyceps [formerly Cordyceps] sinensis) is a fungal/insect complex used in traditional Chinese
medicine to treat fatigue and as a promoter of health, longevity, and
physical performance.388,389 Many active compounds from
cordyceps have been identified and studies have shown their actions to
include anti-inflammation, immune-modulation, and oxidative stress
reduction.390 Furthermore, preclinical research suggests it has
potential as an anti-aging, anti-fatigue, neuroprotective, and aphrodisiac
agent.389 In an animal model of chronic stress, cordyceps
supplementation alleviated depression-like behavior induced by
unpredictable and repeated mild stress. Furthermore, cordyceps treatment
reduced some markers of inflammation and upregulated expression of BDNF.391 Preliminary clinical evidence suggests cordyceps may improve
athletic performance and suppress the exercise-induced rise in cortisol
release, which may help prevent the harmful effects of overtraining.392
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