impact of stress on health essay

Stress and Its Effects on Health Essay

Introduction, physical effects, psychological effects, behavioral effects.

Stress is the emotional strain or tension experienced by an individual due to a reaction toward various demanding and influential situations. The challenging or compelling situations are termed stressors. Stressors can be internal or external and include life changes such as losing a significant figure, low socioeconomic status, relationship problems, occupational challenges, and familial or environmental factors. An individual’s response to stressors influences the outcome of their life. Health is a state of complete social, emotional, and physical well-being and not merely the absence of disease. Stress is a common risk factor for negative health status secondary to negative adaptation and coping with the stressors. Stressors can create a strain on one’s physical, psychological and behavioral well-being, leading to lasting effects that are detrimental to one’s health.

Stress is associated with various physical health impacts on an individual. In an online cross-sectional survey by Keech et al. (2020) to determine the association between stress and the physical and psychological health of police officers, the findings illustrate that stress negatively impacts physical and psychological well-being. One hundred and thirty-four police officers were involved in the study (Keech et al., 2020). The findings demonstrate that stress resulted in various short and long-term physical effects that included increased heart rates, sweating, high blood pressure, and long-term development of the cardiac condition. In addition, stress resulted in the development of gastrointestinal disorders such as peptic ulcer and irritable bowel syndrome. Keech et al. (2020) note that stress’s associated physical health effects are explained by various mechanisms that include overstimulation of the sympathetic nervous system and the hypothalamic-pituitary-adrenocortical axis.

Overstimulation of the sympathetic nervous system results in increased sympathetic actions on the peripheral body organs leading to increased sweat production, heart rate, respiration rate, and urinary and bowel elimination. The study notes that chronic stress without positive adaptation measures results in the progressive development of hypertension, peptic ulcers, and irritable bowel syndrome as long-term effects (Keech et al., 2020). Within the gastrointestinal tract, chronic stress activity on the sympathetic nervous system results in increased parietal cell action. Overactivity of the parietal cells results in excessive gastric acid production, gradually eroding the mucosa, and ulceration occurs.

The effects of stress on the cardiovascular system are explained in a review by Kivimäki & Steptoe (2017) to determine the impact of stress on the development and progression of cardiovascular diseases. In the review, stress is identified to cause cardiovascular conditions secondary to the effects of sustained sympathetic action on heart contractility and peripheral vascular resistance (Kivimäki & Steptoe, 2017). The sympathetic nervous system contributes to normal heart and blood vessel contractility. However, when the system is overstimulated, a surge in contractility above the normal limits ensues, leading to the progressive development of heart conditions.

Psychological well-being incorporates a positive mental health status evidenced by an individual’s satisfaction with life, happiness, rational thinking and decision-making, and positive mood patterns. Stress has been associated with alterations in an individual’s psychological wellness. An explanation for alteration in an individual’s psychological well-being secondary to stress is negative adaptation. Keech et al. (2020) note that an individual’s response to a stressor determines whether stress results in positive or negative effects. In the online cross-sectional survey by Keech et al. (2020), the findings illustrate that pressure resulted in the development of anxiety, depression, and bipolar disorders as long-term effects among the participants. Exposure to stressful situations resulted in progressively developing anxiety among the individual secondary to persistent worry over the issue. The anxiety results in other physical manifestations, including increased heart rate, palpitations, sweating, and altered mobility. Depression and bipolar conditions were also associated with chronic stress secondary to the impacts of stress on neurotransmitter function and nerves.

Similar findings are noted in a cross-sectional study by Zhang et al. (2020) to compare the prevalence and severity of stress-associated mental health symptoms, including anxiety, depression, and insomnia among healthcare workers during the COVID pandemic. Five hundred and twenty-four healthcare workers were involved in the study. The study findings illustrate that 31.3% of the participants developed depression secondary to the stressful working environment, 41.2% reported anxiety, and 39.3% reported sleep disturbances (Zhang et al., 2020). The scientific explanation for the relationship between stress and depression was attributed to the effects of stressful periods on neurotransmitter homeostasis. Chronic stress results in the altered regulation of neurotransmitters in the central nervous system. Alterations in serotonin, norepinephrine, and dopamine resulted in the progressive development of depression and anxiety. Sleep disturbances reported by the participants are attributed to alterations in cortisol hormone homeostasis secondary to overstimulation of the hypothalamic-pituitary-adrenocortical axis.

Stressful situations can also lead to alterations in the behavioral patterns of an individual. The most common behavioral effects secondary to stress include the development of eating disorders, altered sleeping patterns, impaired concentration, and drug abuse especially alcohol. Alterations in sleep and eating patterns are linked to stress’s effects on the hypothalamic-pituitary-adrenocortical axis (HPA). Exposure to stressful events leads to increased activation of the HPA axis with a net effect of increased catecholamine production (adrenaline and noradrenaline) (Moustafa et al., 2018). Increased adrenaline and noradrenaline production results in dysregulation in the eating and sleeping patterns. Sustained high levels of cortisol results in difficulty falling asleep and increased metabolic processes. The biological clock regulates the typical sleeping pattern that relies on producing the sleep hormone melatonin. Melatonin production by the pineal gland is regulated indirectly by the concentration of serum cortisol levels and directly by light perception. Imbalances in the serum concentration cycle secondary to stress results in imbalanced melatonin production and concentration with a net effect of sleeping difficulties.

The emotional strain caused by stress increases the risk of alcohol and other illicit drug use and dependence. Moustafa et al. (2018) conducted an integrative literature review to determine the relationship between childhood trauma, early-life stress, alcohol and drug use, addiction, and abuse. The review findings illustrate that stress increases the risk of alcohol and drug use, addiction, and abuse among the victims. An explanation for the increased risk is the individuals’ lack of identification and implementation of effective coping strategies (Moustafa et al., 2018). Lack of effective coping strategies results in maladaptive measures such as illicit drug use and alcohol consumption. Extensive use of the maladaptive measures results in progressive addiction and drug abuse among individuals with an increased predisposition to other health effects. Alcohol consumption and other illicit drug use over time increase the risk of developing cardiac, respiratory, and liver conditions.

Stress is the emotional strain or tension experienced by an individual due to a reaction toward various demanding and influential situations. Individual response to stressors influences their health. Maladaptive response to stress results in various physical, psychological, and behavioral negative effects. Negative effects of stress on physical health include increased heart rates, sweating, high blood pressure, and long-term development of the cardiac condition. Psychological effects include the development of anxiety, depression, and bipolar disorders. The behavioral effects of stress on an individual include the development of eating disorders, altered sleeping patterns, impaired concentration, and abuse of alcohol and other drugs. Based on the research findings, it is essential for healthcare providers to identify strategic measures and health initiatives to educate and sensitize the community members on effective stress management approaches in all settings to aid in combating the health effects.

Keech, J. J., Cole, K. L., Hagger, M. S., & Hamilton, K. (2020). The association between stress mindset and physical and psychological well being: Testing a stress beliefs model in police officers . Psychology & Health , 35 (11), 1306-1325. Web.

Kivimäki, M., & Steptoe, A. (2017). Effects of stress on the development and progression of cardiovascular disease . Nature Reviews Cardiology , 15 (4), 215–229. Web.

Moustafa, A. A., Parkes, D., Fitzgerald, L., Underhill, D., Garami, J., Levy-Gigi, E., Stramecki, F., Valikhani, A., Frydecka, D., & Misiak, B. (2018). The relationship between childhood trauma, early-life stress, and alcohol and drug use, abuse, and addiction: An integrative review . Current Psychology , 40 (2), 579–584. Web.

Zhang, X., Zhao, K., Zhang, G., Feng, R., Chen, J., Xu, D., Liu, X., Ngoubene-Italy, A. J., Huang, H., Liu, Y., Chen, L., & Wang, W. (2020). Occupational Stress and Mental Health: A comparison between frontline medical staff and non-frontline medical staff during the 2019 novel Coronavirus Disease outbreak . Frontiers in Psychiatry , 11 . Web.

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What Is Stress?

Your Body's Response to a Situation That Requires Attention or Action

Elizabeth Scott, PhD is an author, workshop leader, educator, and award-winning blogger on stress management, positive psychology, relationships, and emotional wellbeing.

• Identifying
• Next in How Stress Impacts Your Health Guide How to Recognize Burnout Symptoms

Stress can be defined as any type of change that causes physical , emotional, or psychological strain. Stress is your body's response to anything that requires attention or action. 

Everyone experiences stress to some degree. The way you respond to stress, however, makes a big difference to your overall well-being.

Verywell / Brianna Gilmartin

Sometimes, the best way to manage your stress involves changing your situation. At other times, the best strategy involves changing the way you respond to the situation.

Developing a clear understanding of how stress impacts your physical and mental health is important. It's also important to recognize how your mental and physical health affects your stress level.

Watch Now: 5 Ways Stress Can Cause Weight Gain

Signs of stress.

Stress can be short-term or long-term. Both can lead to a variety of symptoms, but chronic stress can take a serious toll on the body over time and have long-lasting health effects.

Some common signs of stress include:

• Changes in mood
• Clammy or sweaty palms
• Decreased sex drive
• Difficulty sleeping
• Digestive problems
• Feeling anxious
• Frequent sickness
• Grinding teeth
• Muscle tension, especially in the neck and shoulders
• Physical aches and pains
• Racing heartbeat

Identifying Stress

What does stress feel like? What does stress feel like? It often contributes to irritability, fear, overwork, and frustration. You may feel physically exhausted, worn out, and unable to cope.

Stress is not always easy to recognize, but there are some ways to identify some signs that you might be experiencing too much pressure. Sometimes stress can come from an obvious source, but sometimes even small daily stresses from work, school, family, and friends can take a toll on your mind and body.

If you think stress might be affecting you, there are a few things you can watch for:

• Psychological signs such as difficulty concentrating, worrying, anxiety, and trouble remembering
• Emotional signs such as being angry, irritated, moody, or frustrated
• Physical signs such as high blood pressure, changes in weight, frequent colds or infections, and changes in the menstrual cycle and libido
• Behavioral signs such as poor self-care, not having time for the things you enjoy, or relying on drugs and alcohol to cope

Stress vs. Anxiety

Stress can sometimes be mistaken for anxiety, and experiencing a great deal of stress can contribute to feelings of anxiety. Experiencing anxiety can make it more difficult to cope with stress and may contribute to other health issues, including increased depression, susceptibility to illness, and digestive problems.

Stress and anxiety contribute to nervousness, poor sleep, high blood pressure , muscle tension, and excess worry. In most cases, stress is caused by external events, while anxiety is caused by your internal reaction to stress. Stress may go away once the threat or the situation resolves, whereas anxiety may persist even after the original stressor is gone.

Causes of Stress

There are many different things in life that can cause stress. Some of the main sources of stress include work, finances, relationships, parenting, and day-to-day inconveniences.

Stress can trigger the body’s response to a perceived threat or danger, known as the fight-or-flight response .   During this reaction, certain hormones like adrenaline and cortisol are released. This speeds the heart rate, slows digestion, shunts blood flow to major muscle groups, and changes various other autonomic nervous functions, giving the body a burst of energy and strength.

Originally named for its ability to enable us to physically fight or run away when faced with danger, the fight-or-flight response is now activated in situations where neither response is appropriate—like in traffic or during a stressful day at work.

When the perceived threat is gone, systems are designed to return to normal function via the relaxation response .   But in cases of chronic stress, the relaxation response doesn't occur often enough, and being in a near-constant state of fight-or-flight can cause damage to the body.

Stress can also lead to some unhealthy habits that have a negative impact on your health. For example, many people cope with stress by eating too much or by smoking. These unhealthy habits damage the body and create bigger problems in the long-term.  

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Types of Stress

Not all types of stress are harmful or even negative. Some of the different types of stress that you might experience include:

• Acute stress : Acute stress is a very short-term type of stress that can either be positive or more distressing; this is the type of stress we most often encounter in day-to-day life.
• Chronic stress : Chronic stress is stress that seems never-ending and inescapable, like the stress of a bad marriage or an extremely taxing job; chronic stress can also stem from traumatic experiences and childhood trauma.
• Episodic acute stress : Episodic acute stress is acute stress that seems to run rampant and be a way of life, creating a life of ongoing distress.
• Eustress : Eustress is fun and exciting. It's known as a positive type of stress that can keep you energized. It's associated with surges of adrenaline, such as when you are skiing or racing to meet a deadline. 

4 Main Types of Stress:

The main harmful types of stress are acute stress, chronic stress, and episodic acute stress. Acute stress is usually brief, chronic stress is prolonged, and episodic acute stress is short-term but frequent. Positive stress, known as eustress, can be fun and exciting, but it can also take a toll.

Impact of Stress

Stress can have several effects on your health and well-being. It can make it more challenging to deal with life's daily hassles, affect your interpersonal relationships, and have detrimental effects on your health. The connection between your mind and body is apparent when you examine stress's impact on your life.

Feeling stressed over a relationship, money, or living situation can create physical health issues. The inverse is also true. Health problems, whether you're dealing with high blood pressure or diabetes , will also affect your stress level and mental health. When your brain experiences high degrees of stress , your body reacts accordingly.

Serious acute stress, like being involved in a natural disaster or getting into a verbal altercation, can trigger heart attacks, arrhythmias, and even sudden death. However, this happens mostly in individuals who already have heart disease.

Stress also takes an emotional toll. While some stress may produce feelings of mild anxiety or frustration, prolonged stress can also lead to burnout , anxiety disorders , and depression.

Chronic stress can have a serious impact on your health as well. If you experience chronic stress, your autonomic nervous system will be overactive, which is likely to damage your body.

Stress-Influenced Conditions

• Heart disease
• Hyperthyroidism
• Sexual dysfunction
• Tooth and gum disease

Treatments for Stress

Stress is not a distinct medical diagnosis and there is no single, specific treatment for it. Treatment for stress focuses on changing the situation, developing stress coping skills , implementing relaxation techniques, and treating symptoms or conditions that may have been caused by chronic stress.

Some interventions that may be helpful include therapy, medication, and complementary and alternative medicine (CAM).

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Psychotherapy

Some forms of therapy that may be particularly helpful in addressing symptoms of stress including cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) . CBT focuses on helping people identify and change negative thinking patterns, while MBSR utilizes meditation and mindfulness to help reduce stress levels.

Medication may sometimes be prescribed to address some specific symptoms that are related to stress. Such medications may include sleep aids, antacids, antidepressants, and anti-anxiety medications.

Complementary and Alternative Medicine

Some complementary approaches that may also be helpful for reducing stress include acupuncture, aromatherapy, massage, yoga, and meditation .

Coping With Stress

Although stress is inevitable, it can be manageable. When you understand the toll it takes on you and the steps to combat stress, you can take charge of your health and reduce the impact stress has on your life.

• Learn to recognize the signs of burnout. High levels of stress may place you at a high risk of burnout. Burnout can leave you feeling exhausted and apathetic about your job.   When you start to feel symptoms of emotional exhaustion, it's a sign that you need to find a way to get a handle on your stress.
• Try to get regular exercise. Physical activity has a big impact on your brain and your body . Whether you enjoy Tai Chi or you want to begin jogging, exercise reduces stress and improves many symptoms associated with mental illness.  
• Take care of yourself. Incorporating regular self-care activities into your daily life is essential to stress management. Learn how to take care of your mind, body, and spirit and discover how to equip yourself to live your best life.  
• Practice mindfulness in your life. Mindfulness isn't just something you practice for 10 minutes each day. It can also be a way of life. Discover how to live more mindfully throughout your day so you can become more awake and conscious throughout your life.  

If you or a loved one are struggling with stress, contact the  Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline  at 1-800-662-4357 for information on support and treatment facilities in your area.

For more mental health resources, see our  National Helpline Database .

Cleveland Clinic. Stress .

National institute of Mental Health. I'm so stressed out! Fact sheet .

Goldstein DS. Adrenal responses to stress .  Cell Mol Neurobiol . 2010;30(8):1433–1440. doi:10.1007/s10571-010-9606-9

Stahl JE, Dossett ML, LaJoie AS, et al. Relaxation response and resiliency training and its effect on healthcare resource utilization [published correction appears in PLoS One . 2017 Feb 21;12 (2):e0172874].  PLoS One . 2015;10(10):e0140212. doi:10.1371/journal.pone.0140212

American Heart Association. Stress and Heart Health.

Chi JS, Kloner RA. Stress and myocardial infarction .  Heart . 2003;89(5):475–476. doi:10.1136/heart.89.5.475

Salvagioni DAJ, Melanda FN, Mesas AE, González AD, Gabani FL, Andrade SM. Physical, psychological and occupational consequences of job burnout: A systematic review of prospective studies .  PLoS One . 2017;12(10):e0185781. Published 2017 Oct 4. doi:10.1371/journal.pone.0185781

Bitonte RA, DeSanto DJ 2nd. Mandatory physical exercise for the prevention of mental illness in medical students .  Ment Illn . 2014;6(2):5549. doi:10.4081/mi.2014.5549

Ayala EE, Winseman JS, Johnsen RD, Mason HRC. U.S. medical students who engage in self-care report less stress and higher quality of life .  BMC Med Educ . 2018;18(1):189. doi:10.1186/s12909-018-1296-x

Richards KC, Campenni CE, Muse-Burke JL. Self-care and well-being in mental health professionals: The mediating effects of self-awareness and mindfulness .  J Ment Health Couns . 2010;32(3):247. doi:10.17744/mehc.32.3.0n31v88304423806.

American Psychological Association. 2015 Stress in America .

Krantz DS, Whittaker KS, Sheps DS.  Psychosocial risk factors for coronary heart disease: Pathophysiologic mechanisms .  In R. Allan & J. Fisher,  Heart and mind: The practice of cardiac psychology. American Psychological Association; 2011:91-113. doi:10.1037/13086-004

By Elizabeth Scott, PhD Elizabeth Scott, PhD is an author, workshop leader, educator, and award-winning blogger on stress management, positive psychology, relationships, and emotional wellbeing.

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Stress symptoms: Effects on your body and behavior

Stress symptoms may be affecting your health, even though you might not know it. You may blame sickness for that annoying headache, your sleeping troubles, feeling unwell or your lack of focus at work. But stress may really be the cause.

Common effects of stress

Stress symptoms can affect your body, your thoughts and feelings, and your behavior. Knowing common stress symptoms can help you manage them. Stress that's not dealt with can lead to many health problems, such as high blood pressure, heart disease, stroke, obesity and diabetes.

Act to manage stress

If you have stress symptoms, taking steps to manage your stress can have many health benefits. Check out many possible stress management tips. For example:

• Get regular physical activity on most days of the week.
• Practice relaxation techniques. Try deep breathing, meditation, yoga, tai chi or massage.
• Keep a sense of humor.
• Spend time with family and friends.
• Set aside time for hobbies. Read a book, listen to music or go for a walk. Schedule time for your passions.
• Write in a journal.
• Get enough sleep.
• Eat a healthy, balanced diet.
• Stay away from tobacco and alcohol use, and use of illegal substances.

Aim to find active ways to manage your stress. Idle ways to manage stress that don't get you moving may seem relaxing. But they may make your stress go up over time. Examples are watching television, going on the internet or playing video games.

When to ask for help

If you're not sure if stress is the cause, or if you've taken steps to control your stress but you keep having symptoms, see your health care provider. Your health care provider may want to check for other potential causes. Or think about seeing a counselor or therapist, who can help you find the sources of your stress and learn new coping tools. And if you are concerned about harming yourself, call 911 or a suicide hotline.

Also, get emergency help right away if you have chest pain, especially if you also have shortness of breath; jaw, back, shoulder or arm pain; sweating; dizziness; or nausea. These may be warning signs of a heart attack and not simply stress symptoms.

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• How stress affects your health. American Psychological Association. https://www.apa.org/helpcenter/stress. Accessed Jan. 25, 2023.
• Stress and your health. U.S. Department of Health and Human Services. https://www.womenshealth.gov/mental-health/good-mental-health/stress-and-your-health. Accessed Jan. 24, 2023.
• Manage stress. Healthfinder.gov. http://healthfinder.gov/healthtopics/population/men/mental-health-and-relationships/manage-stress. Accessed Jan. 25, 2023.
• Warning signs of a heart attack. American Heart Association. https://www.heart.org/en/health-topics/heart-attack/warning-signs-of-a-heart-attack#.VsZCDtj2bIU. Accessed Jan. 25, 2023.
• Seaward BL. Essentials of Managing Stress. 5th ed. Jones & Bartlett Learning; 2021.
• Creagan ET (expert opinion). Mayo Clinic. Feb. 14, 2023.

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The impact of stress on body function: A review

Habib yaribeygi.

1 Neurosciences Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

Yunes Panahi

2 Clinical Pharmacy Department, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran

Hedayat Sahraei

Thomas p. johnston.

3 Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, USA

Amirhossein Sahebkar

4 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Any intrinsic or extrinsic stimulus that evokes a biological response is known as stress. The compensatory responses to these stresses are known as stress responses. Based on the type, timing and severity of the applied stimulus, stress can exert various actions on the body ranging from alterations in homeostasis to life-threatening effects and death. In many cases, the pathophysiological complications of disease arise from stress and the subjects exposed to stress, e.g. those that work or live in stressful environments, have a higher likelihood of many disorders. Stress can be either a triggering or aggravating factor for many diseases and pathological conditions. In this study, we have reviewed some of the major effects of stress on the primary physiological systems of humans.

Abbreviations

ACTH: Adrenocorticotropic hormone

CNS: Central nervous system

CRH: Corticotropin releasing hormone

GI: Gastrointestinal

LTP: Long-term potentiation

NMDA : N-methyl-D-aspartate

VTA: Ventral tegmental area

Stress and the Brain Function Complications

For a long time, researchers suggested that hormones have receptors just in the peripheral tissues and do not gain access to the central nervous system (CNS) (Lupien and Lepage, 2001[ 63 ]). However, observations have demonstrated the effect of anti-inflammatory drugs (which are considered synthetic hormones) on behavioral and cognitive disorders and the phenomenon called “Steroid psychosis” (Clark et al., 1952[ 16 ]). In the early sixties, neuropeptides were recognized as compounds devoid of effects on the peripheral endocrine system. However, it was determined that hormones are able to elicit biological effects on different parts of the CNS and play an important role in behavior and cognition (De Kloet, 2000[ 22 ]). In 1968, McEven suggested for the first time that the brain of rodents is capable of responding to glucocorticoid (as one of the operators in the stress cascade). This hypothesis that stress can cause functional changes in the CNS was then accepted (McEwen et al., 1968[ 74 ]). From that time on, two types of corticotropic receptors (glucocorticosteroids and mineralocorticoids) were recognized (de Kloet et al., 1999[ 23 ]). It was determined that the affinity of glucocorticosteroid receptors to cortisol and corticosterone was about one tenth of that of mineralocorticoids (de Kloet et al., 1999[ 23 ]). The hippocampus area has both types of receptors, while other points of the brain have only glucocorticosteroid receptors (de Kloet et al., 1999[ 23 ]).

The effects of stress on the nervous system have been investigated for 50 years (Thierry et al., 1968[ 115 ]). Some studies have shown that stress has many effects on the human nervous system and can cause structural changes in different parts of the brain (Lupien et al., 2009[ 65 ]). Chronic stress can lead to atrophy of the brain mass and decrease its weight (Sarahian et al., 2014[ 100 ]). These structural changes bring about differences in the response to stress, cognition and memory (Lupien et al., 2009[ 65 ]). Of course, the amount and intensity of the changes are different according to the stress level and the duration of stress (Lupien et al., 2009[ 65 ]). However, it is now obvious that stress can cause structural changes in the brain with long-term effects on the nervous system (Reznikov et al., 2007[ 89 ]). Thus, it is highly essential to investigate the effects of stress on different aspects of the nervous system (Table 1 (Tab. 1) ; References in Table 1: Lupien et al., 2001[ 63 ]; Woolley et al., 1990[ 122 ]; Sapolsky et al., 1990[ 99 ]; Gould et al., 1998[ 35 ]; Bremner, 1999[ 10 ]; Seeman et al., 1997[ 108 ]; Luine et al., 1994[ 62 ]; Li et al., 2008[ 60 ]; Scholey et al., 2014[ 101 ]; Borcel et al., 2008[ 9 ]; Lupien et al., 2002[ 66 ]).

Stress and Memory

Memory is one of the important functional aspects of the CNS and it is categorized as sensory, short term, and long-term. Short term memory is dependent on the function of the frontal and parietal lobes, while long-term memory depends on the function of large areas of the brain (Wood et al., 2000[ 121 ]). However, total function of memory and the conversion of short term memory to long-term memory are dependent on the hippocampus; an area of the brain that has the highest density of glucocorticosteroid receptors and also represents the highest level of response to stress (Scoville and Milner, 1957[ 107 ]; Asalgoo et al., 2015[ 1 ]). Therefore, during the past several decades, the relationship between the hippocampus and stress have been hotly debated (Asalgoo et al., 2015[ 1 ]; Lupien and Lepage, 2001[ 63 ]). In 1968, it was proven that there were cortisol receptors in the hippocampus of rats (McEwen et al., 1968[ 74 ]). Later, in 1982, by using specific agonists of glucocorticosteroid and mineralocorticoid receptors, the existence of these two receptors in the brain and hippocampus area of rats was proven (Veldhuis et al., 1982[ 119 ]). It should also be noted that the amygdala is very important to assessing the emotional experiences of memory (Roozendaal et al., 2009[ 91 ]).

The results of past studies have demonstrated the effect of stress on the process of memory (Ghodrat et al., 2014[ 32 ]). Various studies have shown that stress can cause functional and structural changes in the hippocampus section of the brain (McEwen, 1999[ 72 ]). These structural changes include atrophy and neurogenesis disorders (Lupien and Lepage, 2001[ 63 ]). Also, chronic stress and, consequently, an increase in plasma cortisol, leads to a reduction in the number of dendritic branches (Woolley et al., 1990[ 122 ]) and the number of neurons (Sapolsky et al., 1990[ 99 ]), as well as structural changes in synaptic terminals (Sapolsky et al., 1990[ 99 ]) and decreased neurogenesis in the hippocampus tissue (Gould et al., 1998[ 35 ]). Glucocorticosteroids can induce these changes by either effecting the cellular metabolism of neurons (Lawrence and Sapolsky, 1994[ 58 ]), or increasing the sensitivity of hippocampus cells to stimulatory amino acids (Sapolsky and Pulsinelli, 1985[ 98 ]) and/or increasing the level of extracellular glutamate (Sapolsky and Pulsinelli, 1985[ 98 ]).

High concentrations of stress hormones can cause declarative memory disorders (Lupien and Lepage, 2001[ 63 ]). Animal studies have shown that stress can cause a reversible reduction in spatial memory as a result of atrophy of the hippocampus (Luine et al., 1994[ 62 ]). In fact, high plasma concentrations of glucocorticosteroids for extended periods of time can cause atrophy of the hippocampus leading to memory disorders (Issa et al., 1990[ 45 ]). Additionally, people with either Cushing's syndrome (with an increased secretion of glucocorticosteroids), or people who receive high dosages of exogenous synthetic anti-inflammatory drugs, are observed to have atrophy of the hippocampus and associated memory disorders (Ling et al., 1981[ 61 ]). MRI images taken from the brains of people with post-traumatic stress disorder (PTSD) have demonstrated a reduction in the volume of the hippocampus along with neurophysiologic effects such as a weak verbal memory (Bremner, 1999[ 10 ]). Several human studies have suggested that even common therapeutic doses of glucocorticosteroids and dexamethasone can cause problems with explicit memory (Keenan et al., 1995[ 49 ]; Kirschbaum et al., 1996[ 53 ]). Thus, there is an inverse relationship between the level of cortisol and memory (Ling et al., 1981[ 61 ]), such that increasing levels of plasma cortisol following prolonged stress leads to a reduction in memory (Kirschbaum et al., 1996[ 53 ]), which improves when the level of plasma cortisol decreases (Seeman et al., 1997[ 108 ]).

Stress also has negative effects on learning. Results from hippocampus-dependent loading data demonstrate that subjects are not as familiar with a new environment after having been exposed to a new environment (Bremner, 1999[ 10 ]). Moreover, adrenal steroids lead to alteration in long-term potentiation (LTP), which is an important process in memory formation (Bliss and Lømo, 1973[ 7 ]).

Two factors are involved in the memory process during stress. The first is noradrenaline, which creates emotional aspects of memories in the basolateral amygdala area (Joëls et al., 2011[ 47 ]). Secondly, this process is facilitated by corticosteroids. However, if the release of corticosteroids occurs a few hours earlier, it causes inhibition of the amygdala and corresponding behaviors (Joëls et al., 2011[ 47 ]). Thus, there is a mutual balance between these two hormones for creating a response in the memory process (Joëls et al., 2011[ 47 ]).

Stress does not always affect memory. Sometimes, under special conditions, stress can actually improve memory (McEwen and Lupien, 2002[ 71 ]). These conditions include non-familiarity, non-predictability, and life-threatening aspects of imposed stimulation. Under these specific conditions, stress can temporarily improve the function of the brain and, therefore, memory. In fact, it has been suggested that stress can sharpen memory in some situations (Schwabe et al., 2010[ 105 ]). For example, it has been shown that having to take a written examination can improve memory for a short period of time in examination participants. Interestingly, this condition is associated with a decrease in the level of cortisol in the saliva (Vedhara et al., 2000[ 118 ]). Other studies have shown that impending stress before learning occurs can also lead to either an increase in the power of memory (Domes et al., 2002[ 27 ]; Schwabe et al., 2008[ 102 ]), or decrease in the capacity for memory (Diamond et al., 2006[ 26 ]; Kirschbaum et al., 1996[ 53 ]). This paradox results from the type of imposed stress and either the degree of emotional connection to the stressful event (Payne et al., 2007[ 83 ]; Diamond et al., 2007[ 25 ]), or the period of time between the imposing stress and the process of learning (Diamond et al., 2007[ 25 ]).

The process of strengthening memory is usually reinforced after stress (Schwabe et al., 2012[ 103 ]). Various studies on animal and human models have shown that administration of either glucocorticosteroids, or stress shortly after learning has occurred facilitates memory (Schwabe et al., 2012[ 103 ]). Also, it has been shown that glucocorticosteroids (not mineralocorticoids) are necessary to improve learning and memory (Lupien et al., 2002[ 66 ]). However, the retrieval of events in memory after exposure to stress will be decreased (Schwabe et al., 2012[ 103 ]), which may result from the competition of updated data for storage in memory in a stressful state (de Kloet et al., 1999[ 23 ]). Some investigations have shown that either exposure to stress, or injection of glucocorticosteroids before a test to assess retention, decreases the power of memory in humans and rodents (Schwabe and Wolf, 2009[ 104 ]).

In summary, it has been concluded that the effect of stress on memory is highly dependent on the time of exposure to the stressful stimulus and, in terms of the timing of the imposed stress, memory can be either better or worse (Schwabe et al., 2012[ 103 ]). Moreover, recent studies have shown that using a specific-timed schedule of exposure to stress not only affects hippocampus-dependent memory, but also striatum-dependent memory, which highlights the role of timing of the imposed stressful stimulus (Schwabe et al., 2010[ 105 ]).

Stress, Cognition and Learning

Cognition is another important feature of brain function. Cognition means reception and perception of perceived stimuli and its interpretation, which includes learning, decision making, attention, and judgment (Sandi, 2013[ 95 ]). Stress has many effects on cognition that depend on its intensity, duration, origin, and magnitude (Sandi, 2013[ 95 ]). Similar to memory, cognition is mainly formed in the hippocampus, amygdala, and temporal lobe (McEwen and Sapolsky, 1995[ 73 ]). The net effect of stress on cognition is a reduction in cognition and thus, it is said that any behavioral steps undertaken to reduce stress leads to increase in cognition (Scholey et al., 2014[ 101 ]). In fact, stress activates some physiological systems, such as the autonomic nervous system, central neurotransmitter and neuropeptide system, and the hypothalamus-pituitary-adrenal axis, which have direct effects on neural circuits in the brain involved with data processing (Sandi, 2013[ 95 ]). Activation of stress results in the production and release of glucocorticosteroids. Because of the lipophilic properties of glucocorticosteroids, they can diffuse through the blood-brain barrier and exert long-term effects on processing and cognition (Sandi, 2013[ 95 ]).

It appears that being exposed to stress can cause pathophysiologic changes in the brain, and these changes can be manifested as behavioral, cognitive, and mood disorders (Li et al., 2008[ 60 ]). In fact, studies have shown that chronic stress can cause complications such as increased IL-6 and plasma cortisol, but decreased amounts of cAMP responsive element binding protein and brain-derived neurotrophic factor (BDNF), which is very similar to what is observed in people with depression and mood disorders that exhibit a wide range of cognitive problems (Song et al., 2006[ 114 ]). Additionally, the increased concentrations of inflammatory factors, like interleukins and TNF-α (which play an important role in creating cognitive disorders), proves a physiologic relationship between stress and mood-based cognitive disorders (Solerte et al., 2000[ 113 ]; Marsland et al., 2006[ 68 ]; Li et al., 2008[ 60 ]). Studies on animals suggest that cognitive disorders resulting from stress are created due to neuroendocrine and neuroamine factors and neurodegenerative processes (Li et al., 2008[ 60 ]). However, it should be noted that depression may not always be due to the over activation of the physiological-based stress response (Osanloo et al., 2016[ 81 ]).

Cognitive disorders following exposure to stress have been reported in past studies (Lupien and McEwen, 1997[ 64 ]). Stress has effects on cognition both acutely (through catecholamines) and chronically (through glucocorticosteroids) (McEwen and Sapolsky, 1995[ 73 ]). Acute effects are mainly caused by beta-adrenergic effects, while chronic effects are induced in a long-term manner by changes in gene expression mediated by steroids (McEwen and Sapolsky, 1995[ 73 ]). In general, many mechanisms modulate the effects of stress on cognition (McEwen and Sapolsky, 1995[ 73 ]; Mendl, 1999[ 75 ]). For instance, adrenal steroids affect the function of the hippocampus during cognition and memory retrieval in a biphasic manner (McEwen and Sapolsky, 1995[ 73 ]). In chronic stress, these steroids can destroy neurons with other stimulatory neurotransmitters (Sandi, 2013[ 95 ]). Exposure to stress can also cause disorders in hippocampus-related cognition; specifically, spatial memory (Borcel et al., 2008[ 9 ]; Sandi et al., 2003[ 96 ]). Additionally, stress can halt or decrease the genesis of neurons in the dentate gyrus area of the hippocampus (this area is one of the limited brain areas in which neurogenesis occurs in adults) (Gould and Tanapat, 1999[ 34 ]; Köhler et al., 2010[ 54 ]). Although age is a factor known to affect cognition, studies on animals have demonstrated that young rats exposed to high doses of adrenal steroids show the same level of decline in their cognition as older adult animals with normal plasma concentrations of glucocorticoids (Landfield et al., 1978[ 57 ]). Also, a decrease in the secretion of glucocorticosteroids causes preservation of spatial memory in adults and has also been shown to have neuroprotective effects (Montaron et al., 2006[ 78 ]). Other studies have shown that stress (or the injection of adrenal steroids) results in varied effects on cognition. For instance, injection of hydrocortisone at the time of its maximum plasma concentration (in the afternoon) leads to a decrease in reaction time and improves cognition and memory (Lupien et al., 2002[ 66 ]).

In summary, the adverse effects of stress on cognition are diverse and depend on the type, timing, intensity, and duration (Sandi, 2013[ 95 ]). Generally, it is believed that mild stress facilitates an improvement in cognitive function, especially in the case of virtual or verbal memory. However, if the intensity of stress passes beyond a predetermined threshold (which is different in each individual), it causes cognitive disorders, especially in memory and judgment. The disruption to memory and judgment is due to the effects of stress on the hippocampus and prefrontal cortex (Sandi, 2013[ 95 ]). Of course, it must be realized that factors like age and gender may also play a role in some cognitive disorders (Sandi, 2013[ 95 ]). Importantly, it should be emphasized that different people may exhibit varied responses in cognition when exposed to the very same stressful stimulus (Hatef et al., 2015[ 39 ]).

Stress and Immune System Functions

The relationship between stress and the immune system has been considered for decades (Khansari et al., 1990[ 50 ]; Dantzer and Kelley, 1989[ 21 ]). The prevailing attitude between the association of stress and immune system response has been that people under stress are more likely to have an impaired immune system and, as a result, suffer from more frequent illness (Khansari et al., 1990[ 50 ]). Also, old anecdotes describing resistance of some people to severe disease using the power of the mind and their thought processes, has promoted this attitude (Khansari et al., 1990[ 50 ]). In about 200 AC, Aelius Galenus (Galen of Pergamon) declared that melancholic women (who have high levels of stress and, thus, impaired immune function) are more likely to have cancer than women who were more positive and exposed to less stress (Reiche et al., 2004[ 88 ]). This may be the first recorded case about the relationship between the immune system and stress. In an old study in the early 1920's, researchers found that the activity of phagocytes in tuberculosis decreased when emotional stress was induced. In fact, it was also suggested that living with stress increases the risk of tuberculosis by suppressing the immune system (Ishigami, 1919[ 44 ]). Following this study, other researchers suggested that the probability of disease appearance increases following a sudden, major, and extremely stressful life style change (Holmes and Rahe, 1967[ 41 ]; Calabrese et al., 1987[ 12 ]).

Over the past several decades, there have been many studies investigating the role of stress on immune system function (Dantzer and Kelley, 1989[ 21 ]; Segerstrom and Miller, 2004[ 109 ]). These studies have shown that stress mediators can pass through the blood-brain barrier and exert their effects on the immune system (Khansari et al., 1990[ 50 ]). Thus, the effect of stress on the immune system is now an accepted relationship or association.

Stress can affect the function of the immune system by modulating processes in the CNS and neuroendocrine system (Khansari et al., 1990[ 50 ]; Kiecolt-Glaser and Glaser, 1991[ 51 ]). Following stress, some neuroendocrine and neural responses result in the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and other stress mediators (Carrasco and Van de Kar, 2003[ 13 ]). However, evidence suggests that the lymphatic system, which is a part of the immune system, also plays a role in releasing these mediators (Khansari et al., 1990[ 50 ]). For instance, thymus peptides, such as thymopentine, thymopoietin, and thymosin fraction-5, cause an increase in ACTH production (Goya et al., 1993[ 36 ]). Additionally, the existence of CRH in thymus has been proven (Redei, 1992[ 87 ]). It has also been proven that interleukin-1 released from phagocytes has a role in ACTH secretion (Berkenbosch et al., 1987[ 4 ]). On the other hand, natural or synthetic glucocorticosteroids (which are the final stress operators) are known as anti-inflammatory drugs and immune suppressants and their role in the inhibition of lymphocytes and macrophages has been demonstrated as well (Elenkov et al., 1999[ 28 ]; Reiche et al., 2004[ 88 ]). Moreover, their role in inhibiting the production of cytokines and other immune mediators and decreasing their effect on target cells during exposure to stress has also been determined (Reiche et al., 2004[ 88 ]).

In addition to adrenal steroids, other hormones are affected during stress. For example, the secretion of growth hormone will be halted during severe stress. A study showed that long-term administration of CRH into the brain ventricles leads to a cessation in the release of growth hormone (Rivier and Vale, 1985[ 90 ]). Stress also causes the release of opioid peptides to be changed during the time period over which the person is exposed to stress (McCarthy et al., 2001[ 70 ]). In fact, stress modifies the secretion of hormones that play a critical role in the function of the immune system (Khansari et al., 1990[ 50 ]). To date, it has been shown that various receptors for a variety of hormones involved in immune system function are adversely affected by stress. For example, ACTH, vasoactive intestinal peptide (VIP), substance P, growth hormone, prolactin, and steroids all have receptors in various tissues of the immune system and can modulate its function (De la Fuente et al., 1996[ 24 ]; Gala, 1991[ 30 ]; Mantyh, 1991[ 67 ]). In addition, active immune cells are also able to secrete several hormones; thus, some researchers believe that these hormones, as mediators of immune system, play a significant role in balancing its function (Blalock et al., 1985[ 6 ]).

Severe stress can lead to malignancy by suppressing the immune system (Reiche et al., 2004[ 88 ]). In fact, stress can decrease the activity of cytotoxic T lymphocytes and natural killer cells and lead to growth of malignant cells, genetic instability, and tumor expansion (Reiche et al., 2004[ 88 ]). Studies have shown that the plasma concentration of norepinephrine, which increases after the induction stress, has an inverse relationship with the immune function of phagocytes and lymphocytes (Reiche et al., 2004[ 88 ]). Lastly, catecholamines and opioids that are released following stress have immune-suppressing properties (Reiche et al., 2004[ 88 ]).

Stress and the Function of the Cardiovascular System

The existence of a positive association between stress and cardiovascular disease has been verified (Rozanski et al., 1999[ 93 ]). Stress, whether acute or chronic, has a deleterious effect on the function of the cardiovascular system (Rozanski et al., 1999[ 93 ]; Kario et al., 2003[ 48 ]; Herd, 1991[ 40 ]). The effects of stress on the cardiovascular system are not only stimulatory, but also inhibitory in nature (Engler and Engler, 1995[ 29 ]). It can be postulated that stress causes autonomic nervous system activation and indirectly affects the function of the cardiovascular system (Lazarus et al., 1963[ 59 ]; Vrijkotte et al., 2000[ 120 ]). If these effects occur upon activation of the sympathetic nervous system, then it mainly results in an increase in heart rate, strength of contraction, vasodilation in the arteries of skeletal muscles, a narrowing of the veins, contraction of the arteries in the spleen and kidneys, and decreased sodium excretion by the kidneys (Herd, 1991[ 40 ]). Sometimes, stress activates the parasympathetic nervous system (Pagani et al., 1991[ 82 ]). Specifically, if it leads to stimulation of the limbic system, it results in a decrease, or even a total stopping of the heart-beat, decreased contractility, reduction in the guidance of impulses by the heart stimulus-transmission network, peripheral vasodilatation, and a decline in blood pressure (Cohen et al., 2000[ 17 ]). Finally, stress can modulate vascular endothelial cell function and increase the risk of thrombosis and ischemia, as well as increase platelet aggregation (Rozanski et al., 1999[ 93 ]).

The initial effect of stress on heart function is usually on the heart rate (Vrijkotte et al., 2000[ 120 ]). Depending upon the direction of the shift in the sympatho-vagal response, the heart beat will either increase or decrease (Hall et al., 2004[ 38 ]). The next significant effect of stress on cardiovascular function is blood pressure (Laitinen et al., 1999[ 56 ]). Stress can stimulate the autonomic sympathetic nervous system to increase vasoconstriction, which can mediate an increase in blood pressure, an increase in blood lipids, disorders in blood clotting, vascular changes, atherogenesis; all, of which, can cause cardiac arrhythmias and subsequent myocardial infarction (Rozanski et al., 1999[ 93 ]; Vrijkotte et al., 2000[ 120 ]; Sgoifo et al., 1998[ 111 ]). These effects from stress are observed clinically with atherosclerosis and leads to an increase in coronary vasoconstriction (Rozanski et al., 1999[ 93 ]). Of course, there are individual differences in terms of the level of autonomic-based responses due to stress, which depends on the personal characteristics of a given individual (Rozanski et al., 1999[ 93 ]). Thus, training programs for stress management are aimed at reducing the consequences of stress and death resulting from heart disease (Engler and Engler, 1995[ 29 ]). In addition, there are gender-dependent differences in the cardiovascular response to stress and, accordingly, it has been estimated that women begin to exhibit heart disease ten years later that men, which has been attributed to the protective effects of the estrogen hormone (Rozanski et al., 1999[ 93 ]).

Studies have shown that psychological stress can cause alpha-adrenergic stimulation and, consequently, increase heart rate and oxygen demand (Rozanski et al., 1998[ 92 ], 1999[ 93 ]; Jiang et al., 1996[ 46 ]). As a result, coronary vasoconstriction is enhanced, which may increase the risk of myocardial infarction (Yeung et al., 1991[ 124 ]; Boltwood et al., 1993[ 8 ]; Dakak et al., 1995[ 20 ]). Several studies have demonstrated that psychological stress decreases the microcirculation in the coronary arteries by an endothelium-dependent mechanism and increases the risk of myocardial infarction (Dakak et al., 1995[ 20 ]). On the other hand, mental stress indirectly leads to potential engagement in risky behaviors for the heart, such as smoking, and directly leads to stimulation of the neuroendocrine system as part of the autonomic nervous system (Hornstein, 2004[ 43 ]). It has been suggested that severe mental stress can result in sudden death (Pignalberi et al., 2002[ 84 ]). Generally, stress-mediated risky behaviors that impact cardiovascular health can be summarized into five categories: an increase in the stimulation of the sympathetic nervous system, initiation and progression of myocardial ischemia, development of cardiac arrhythmias, stimulation of platelet aggregation, and endothelial dysfunction (Wu, 2001[ 123 ]).

Stress and Gastrointestinal Complications

The effects of stress on nutrition and the gastrointestinal (GI) system can be summarized with two aspects of GI function.

First, stress can affect appetite (Bagheri Nikoo et al., 2014[ 2 ]; Halataei et al., 2011[ 37 ]; Ranjbaran et al., 2013[ 86 ]). This effect is related to involvement of either the ventral tegmental area (VTA), or the amygdala via N-methyl-D-aspartate (NMDA) glutamate receptors (Nasihatkon et al., 2014[ 80 ]; Sadeghi et al., 2015[ 94 ]). However, it should also be noted that nutrition patterns have effects on the response to stress (Ghanbari et al., 2015[ 31 ]), and this suggests a bilateral interaction between nutrition and stress.

Second, stress adversely affects the normal function of GI tract. There are many studies concerning the effect of stress on the function of the GI system (Söderholm and Perdue, 2001[ 112 ]; Collins, 2001[ 18 ]). For instance, studies have shown that stress affects the absorption process, intestinal permeability, mucus and stomach acid secretion, function of ion channels, and GI inflammation (Collins, 2001[ 18 ]; Nabavizadeh et al., 2011[ 79 ]). Stress also increases the response of the GI system to inflammation and may reactivate previous inflammation and accelerate the inflammation process by secretion of mediators such as substance P (Collins, 2001[ 18 ]). As a result, there is an increase in the permeability of cells and recruitment of T lymphocytes. Lymphocyte aggregation leads to the production of inflammatory markers, activates key pathways in the hypothalamus, and results in negative feedback due to CRH secretion, which ultimately results in the appearance of GI inflammatory diseases (Collins, 2001[ 18 ]). This process can reactivate previous silent colitis (Million et al., 1999[ 76 ]; Qiu et al., 1999[ 85 ]). Mast cells play a crucial role in stress-induced effects on the GI system, because they cause neurotransmitters and other chemical factors to be released that affect the function of the GI system (Konturek et al., 2011[ 55 ]).

Stress can also alter the functional physiology of the intestine (Kiliaan et al., 1998[ 52 ]). Many inflammatory diseases, such as Crohn's disease and other ulcerative-based diseases of the GI tract, are associated with stress (Hommes et al., 2002[ 42 ]). It has been suggested that even childhood stress can lead to these diseases in adulthood (Schwartz and Schwartz, 1983[ 106 ]). Irritable bowel syndrome, which is a disease with an inflammatory origin, is highly related to stress (Gonsalkorale et al., 2003[ 33 ]). Studies on various animals suggest the existence of inflammatory GI diseases following induction of severe stress (Qiu et al., 1999[ 85 ]; Collins et al., 1996[ 19 ]). Additionally, pharmacological interventions, in an attempt to decrease the response of CRH to stress, have been shown to result in an increase in GI diseases in rats (Million et al., 1999[ 76 ]).

Altering the permeability of the mucosal membrane by perturbing the functions of mucosal mast cells may be another way that stress causes its effects on the GI system, since this is a normal process by which harmful and toxic substances are removed from the intestinal lumen (Söderholm and Perdue, 2001[ 112 ]). Also, stress can both decrease the removal of water from the lumen, as well as induce sodium and chloride secretion into the lumen. This most likely occurs by increasing the activity of the parasympathetic nervous system (Barclay and Turnberg, 1987[ 3 ]). Moreover, physical stress, such as trauma or surgery, can increase luminal permeability (Söderholm and Perdue, 2001[ 112 ]) (Table 2 (Tab. 2) ; References in Table 2: Halataei et al., 2011[ 37 ]; Ranjbaran et al., 2013[ 86 ]; Mönnikes et al., 2001[ 77 ]; Collins, 2001[ 18 ]; Nabavizadeh et al., 2011[ 79 ]; Barclay and Turnberg, 1987[ 3 ]; Million et al., 1999[ 76 ]; Gonsalkorale et al., 2003[ 33 ]).

Stress also affects movement of the GI tract. In this way, it prevents stomach emptying and accelerates colonic motility (Mönnikes et al., 2001[ 77 ]). In the case of irritable bowel syndrome, stress increases the movement (contractility and motility) of the large intestine (Mönnikes et al., 2001[ 77 ]). Previous studies have revealed that CRH increases movement in the terminal sections of the GI tract and decreases the movements in the proximal sections of the GI tract (Mönnikes et al., 2001[ 77 ]). A delay in stomach emptying is likely accomplished through CRH-2 receptors, while type 1 receptors affect the colon (Mönnikes et al., 2001[ 77 ]). The effects produced by CRH are so prominent that CRH is now considered an ideal candidate for the treatment of irritable bowel syndrome (Martinez and Taché, 2006[ 69 ]). When serotonin is released in response to stress (Chaouloff, 2000[ 14 ]), it leads to an increase in the motility of the colon by stimulating 5HT-3 receptors (Mönnikes et al., 2001[ 77 ]). Moreover, it has also been suggested that stress, especially mental and emotional types of stress, increase visceral sensitivity and activate mucosal mast cells (Mönnikes et al., 2001[ 77 ]). Stimulation of the CNS by stress has a direct effect on GI-specific nervous system ( i.e. , the myenteric system or plexus) and causes the above mentioned changes in the movements of the GI tract (Bhatia and Tandon, 2005[ 5 ]). In fact, stress has a direct effect on the brain-bowel axis (Konturek et al., 2011[ 55 ]). Various clinical studies have suggested a direct effect of stress on irritable bowel syndrome, intestinal inflammation, and peptic ulcers (Konturek et al., 2011[ 55 ]).

In conclusion, the effects of stress on the GI system can be classified into six different actions: GI tract movement disorders, increased visceral irritability, altered rate and extent of various GI secretions, modified permeability of the intestinal barrier, negative effects on blood flow to the GI tract, and increased intestinal bacteria counts (Konturek et al., 2011[ 55 ]).

Stress and the Endocrine System

There is a broad and mutual relationship between stress and the endocrine system. On one hand, stress has many subtle and complex effects on the activity of the endocrine system (Sapolsky, 2002[ 97 ]; Charmandari et al., 2005[ 15 ]), while on the other hand, the endocrine system has many effects on the response to stress (Ulrich-Lai and Herman, 2009[ 117 ]; Selye, 1956[ 110 ]). Stress can either activate, or change the activity of, many endocrine processes associated with the hypothalamus, pituitary and adrenal glands, the adrenergic system, gonads, thyroid, and the pancreas (Tilbrook et al., 2000[ 116 ]; Brown-Grant et al., 1954[ 11 ]; Thierry et al., 1968[ 115 ]; Lupien and McEwen, 1997[ 64 ]). In fact, it has been suggested that it is impossible to separate the response to stress from the functions of the endocrine system. This premise has been advanced due to the fact that even a minimal amount of stress can activate the hypothalamic-pituitary-adrenal axis, which itself is intricately involved with the activation of several different hormone secreting systems (Sapolsky, 2002[ 97 ]). In different locations throughout this article, we have already discussed the effects of stress on hormones and various endocrine factors and, thus, they will not be further addressed.

Altogether, stress may induce both beneficial and harmful effects. The beneficial effects of stress involve preserving homeostasis of cells/species, which leads to continued survival. However, in many cases, the harmful effects of stress may receive more attention or recognition by an individual due to their role in various pathological conditions and diseases. As has been discussed in this review, various factors, for example, hormones, neuroendocrine mediators, peptides, and neurotransmitters are involved in the body's response to stress. Many disorders originate from stress, especially if the stress is severe and prolonged. The medical community needs to have a greater appreciation for the significant role that stress may play in various diseases and then treat the patient accordingly using both pharmacological (medications and/or nutraceuticals) and non-pharmacological (change in lifestyle, daily exercise, healthy nutrition, and stress reduction programs) therapeutic interventions. Important for the physician providing treatment for stress is the fact that all individuals vary in their response to stress, so a particular treatment strategy or intervention appropriate for one patient may not be suitable or optimal for a different patient.

Yunes Panahi and Amirhossein Sahebkar (Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, P.O. Box: 91779-48564, Iran; Tel: 985118002288, Fax: 985118002287, E-mail: [email protected], [email protected]) contributed equally as corresponding authors.

Conflict of interest

The authors declare that have no conflict of interest in this study.

Acknowledgement

The authors would like to thank the "Neurosciences Research Center of Baqiyatallah University of Medical Sciences" and the “Clinical Research Development Center of Baqiyatallah (a.s.) Hospital” for providing technical supports.

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The editors of the Harvard Health letter maintain that there is evidence that individuals who are chronically stressed possess an increased risk of cancer and heart disease.  Although concrete evidence may not be available to substantiate this claim, other researchers and medical professionals continue to argue that the negative effects of stress are quite harmful on the human body.  “Stress is known to significantly alter one’s health, affecting such areas as immune function, heart disease, and susceptibility to cancer” (“Effects of Stress”, 2009, p. 9).  It is clear that stress can dangerously lower the immune system and force the body to be ill equipped to defend itself against harmful disease-causing agents.  Furthermore, research also shows that “stress decreases uterine receptivity by a pathway that is independent of the ovary in infertile women, state researchers in Japan” (“Effects of Stress”, 2009, p. 9).  In other words, it has been proven that stress can make women infertile or at least make the process of conceiving a child much more difficult than in ideal circumstances.  These negative health effects caused directly or indirectly by stress are clear examples that stress does harm the health of human beings each and every day.

However, a study by Coventry et al. (2009) showed marked results that the addition of stress had no negative or positive impact in males or females upon contracting cases of depression (p. 487).  This could be a case to support the claims of author Christopher Caldwell who argues that no one including doctors, can come to an agreement on what stress is, so stress can not be blamed as the cause of disease.  On the other hand, this is a separate case study designed only to examine the impact that stress has on contracting, maintaining and advancing cases of depression.  The case does not support that stress is not a causal agent for other health defects including those mentioned above such as chronic heart disease, immune deficiency and cancer.

I believe that stress is a definite causal factor for health problems in everyday life.  We live a hectic lifestyle that forces many people to get little sleep and have heightened stressful experiences.  I have had a case on Mono and brief period of back spasms that the doctors always told me were caused directly by stress.  When stress increases, I get tired and sometimes even exhausted.  Exhaustion reduces the immune system and can allow for harmful bacteria and viruses to enter the body and cause great damage.  Sometimes people with healthier immune systems are more likely to not experience these effects rather than people with unhealthier lifestyles that reduce the immune system.  Nobody can tell for sure when someone will become ill due to stress; however, it is clear that under the right circumstances stress can cause much damage to the human body.

To avoid stress, I do whatever I can to try to have a healthy outlet for any stress that I experience in everyday life.  For instance, I try to work out at least three times a week.  I know that we are supposed to work out more than that, but with a busy lifestyle it is difficult to fit exercise in each day.  Nevertheless, exercise is a great productive outlet for stress that reduces the stress levels significantly and keeps the body healthy, which also keeps the immune system strong.  I also make it a point to resolve any issues that I experience in my life as much as possible.  When people have stressful issues in their lives that go unresolved, it can continue to increase the stress levels and be very unhealthy.  If I have arguments with friends or feel disrespected, I try to have a constructive conversation to resolve any problems and keep my stress levels low.  This is great when I do not have to constantly worry about situations and problems in my life.  We have enough to worry about; I would much rather not become a victim of stress because of a hectic lifestyle and increased stress levels due to my own inaction.

(2009). Effects of Stress. Fertility Weekly , 9. Retrieved from Academic Search Complete database.

(2009). Stress Adds to Overweight Worries. Tufts University Health & Nutrition Letter , 27 (8), 8. Retrieved from Academic Search Complete database.

Coventry, W., Medland, S., Wray, N., Thorsteinsson, E., Heath, A., & Byrne, B. (2009). Phenotypic and Discordant-Monozygotic Analyses of Stress and Perceived Social Support as Antecedents to or Sequelae of Risk for Depression. Twin Research & Human Genetics , 12 (5), 469-488. doi:10.1375/twin.12.5.469.

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Home / Mental Health / How to deal with stress: Insight from Mayo Clinic experts

How to deal with stress: Insight from Mayo Clinic experts

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Stress is one of the truly universal human experiences — and no one exactly enjoys being frazzled or feeling unable to handle a new situation.

However, stress also can be a powerful, and even positive, motivator. For example, starting a new job might make you sweat, but it also may be deeply satisfying to take on a new professional challenge. Ideally, stress can lead to personal growth and make you more adaptable in new or uncertain situations.

But when stress becomes too overwhelming or chronic — like during a global pandemic, the loss of a loved one or extended financial difficulties — stress can undermine your quality of life. Chronic stress, for example, can not only cause day-to-day issues with concentration, fatigue and headaches, but can put you at higher risk of many health problems like heart disease, depression, cancer and insomnia.

It is possible to better manage and reduce stress. Of course, there is no magic bullet to remove life’s stressors. In fact, some stressors aren’t just personal but systemic — forces like poverty, oppression, racism and sexism can’t be addressed with simple tweaks on an individual level. But there are ways to shape your own relationship to stress and invite in more opportunities for joy, connection and rest.

• Take stock of how stress shows up in your life. What usually causes the most stress? Are there certain environments, people or situations that weigh on you? While it’s not always possible to avoid stressors, consider how you can better mitigate their impact. You may, for example, change how you interact with someone, ask for help, strengthen work-life boundaries, step back from a project, or shift toward more positive talk about yourself and your circumstances.
• Consider how you might invest in your holistic well-being. Of course, maintaining a good diet, exercise and sleep routine can help you be more resilient. Connecting with loved ones might be deprioritized during stressful periods, but research has shown that strong social support helps people better weather stress . This can be as simple as catching up with a friend, going for a distraction-free walk with your partner or talking through a problem with a trusted confidant. In moments of stress, practices like guided meditation, progressive muscle relaxation, and deep breathing can help calm you and clear your mind.

There are many strategies and resources to choose from, and luckily there are no wrong answers. Focus on the activities and relationships that bring you ease, joy or a little bit of calm in your hectic life. To help get you started, Mayo Clinic experts share how they manage stress in their own lives.

Katherine “Kate” A. Zeratsky, R.D.N., specialty editor for the Mayo Clinic Nutrition and Healthy Eating Guide

“Exercise has always been my go-to, before I even recognized what stress was. Now when stressed, I can also appreciate that in addition to the physical movement, that changes in how I’m breathing helps reduce stress. Paying attention to my breathing (even at rest) helps in my stress management. If I can be outside or even look out a window while exercising, that is a bonus — joy!”

Paul Yardley, Mayo Clinic well-being specialist

“Acceptance that some things are out of my control, [in addition to] gratitude, exercise, paced breathing, being with my dogs.”

Juliana “Jewel” Kling, M.D., M.P.H., professor of medicine and chair of Women’s Health Internal Medicine

“Exercise. Even a small walk can help reduce stress. Sometimes more vigorous exercise is what you need — cue the Peloton!”

Craig N. Sawchuk, Ph.D., L.P., professor of psychology, co-chair of Clinical Practice and co-chair of the Division of Integrated Behavioral Health, Department of Psychiatry and Psychology

“Coffee! Absolutely love coffee. Although caffeine can certainly run the risk of adding to physical symptoms of stress, the smell, culture and sense of community that comes with coffee instantly helps me de-stress. My wife, kids, and I love to do our Starbucks runs and explore new locations during our travels. Snagging a coffee with my colleagues at work is one of the things that I truly look forward to during my work week — it’s a great way to connect, collaborate and support each other.”

Daniel Roberts, M.D., hospitalist, senior medical editor of the Mayo Clinic Health Letter

“Reading and re-reading David Allen’s “ Getting Things Done: The Art of Stress Free Productivity ” made me aware of how much of my stress was from open loops I wasn’t dealing with because I assumed I’d get to them when inspiration struck or I had nothing else going on. As I’ve gotten older — and after the pandemic shifted a lot of my nonclinical work to home, where I had been lousy for decades at setting work/family boundaries — I’ve become more of a list-keeper, even for the mundane stuff. Knowing it’s on the list and that I’ll get to it at an actual time that isn’t right before the deadline, allows me to work when I need to work and not work when I need to be a husband and father.”

Tara M. Schmidt, M.Ed., R.D.N., lead dietitian for the Mayo Clinic Diet

“While I do love a good book, true stress relief for me is when I can talk openly with others. It may be my best friend and I reminding each other that toddlers are toddlers or talking through an overwhelming project with a colleague. I don’t feel as alone when someone I’m close to shares a similar experience or can validate my point of view. I tend to come out of the conversation feeling less overwhelmed.”

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The Surprising Benefits of Stress

Daniela Kaufer is an associate professor at UC Berkeley who studies the biology of stress, examining at the molecular level how the brain responds to anxiety and traumatic events. Her recent findings reveal the difference between good stress and bad stress, as well as pointers for how to respond to stressful events in a healthy way. She was interviewed by health writer Peter Jaret for the Berkeley Wellness newsletter, where this Q&A originally appeared .

Peter Jaret: Most of us think of stress as a bad thing. Can stress be good for you?

Daniela Kaufer: The prevailing idea in our culture is that stress is bad. People complain about being stressed out. But we’re learning that moderate amounts of stress have powerful benefits. The stress response is designed to help us react when something potentially threatening happens, to help us deal with it and learn from it. Our research shows that moderate, short-lived stress can improve alertness and performance and boost memory.

PJ: How do you measure the effects of stress?

DK: In our work, we study the effects of stress on rats, and we look specifically at the growth of stem cells in a part of the brain called the hippocampus. The hippocampus is involved in the stress response, and it’s also very important for learning and memory. We’ve found that when rats are exposed to moderate stress for a short time—being immobilized for a few hours, for instance—stem cell growth is stimulated, and those cells go on to form neurons, or brain cells. A couple of weeks later, tests show improvements in learning and memory. We’ve shown that the specific cells generated during stress have become activated. But when the animals are exposed to chronic or intense stress—being immobilized for days at a time, for example, or being immobilized and then exposed to the smell of a predator—stem cell growth is suppressed and fewer brain cells are generated.

PJ: What about people? Can manageable amounts of stress boost brain power?

DK: We think the same thing happens in people. Manageable stress increases alertness and performance. And by encouraging the growth of stem cells that become brain cells, stress improves memory. The increase in stem cells and neuron generation makes sense from an adaptive point of view. If an animal encounters a predator and manages to escape, it’s important to remember where and when that encounter happened, to avoid it in the future. If you’re walking down an alley and somebody threatens you, it’s important to remember exactly where you were in order to avoid that alley in the future. The brain is constantly responding to stress. Extreme or chronic stress can have a negative effect. But moderate and short-lived stress—like an upcoming exam or preparing to deliver a speech in public—improves cognitive performance and memory.

PJ: When does too much stress become harmful?

DK: Individuals vary widely in how they respond to stress. The same stressor may be manageable for one person and overwhelming for another, depending in part on perception. People who feel resilient and confident that they can manage stress are much less likely to be overwhelmed by it—and more likely to have a healthy response—than people who think of stress as bad. Another factor is control. Stress is much less likely to be harmful if people have some control over the situation. A tight deadline is stressful but manageable if you have the ability to meet it. If not, if you feel helpless, the stress is more likely to be harmful. Early life experiences also shape how people respond to stress. If you have a lot of stress in your early life, you may be more vulnerable to the harmful effects of stress. Research by Rachel Yehuda, a scientist at the Icahn School of Medicine at Mount Sinai and the James J. Peters Veterans Affairs Medical Center in New York, has shown that Holocaust survivors have increased levels of stress hormones. Her most recent research shows that even offspring of Holocaust survivors have higher stress hormone levels.

PJ: Your work focuses on the effects of stress on the brain. Does stress affect other systems of the body?

DK: Chronic stress can constrict blood vessels and increase the risk of cardiovascular disease . Research shows that too much stress can suppress the immune system . Ours and other research has shown that chronic stress also reduces fertility in animals. In female mice, for instance, stress lowers libido, reduces fertility, and increases the risk of miscarriage. We also know that extreme stress can lead to post traumatic stress disorder, which is an area I’m very interested in. As I’ve said, it’s important to remember threats. But it’s also important to be able to forget them as new experiences come along. Let’s say a man with a long white beard frightens you as a child. It’s healthy to begin to forget that memory as you come to see that men with long white beards aren’t inherently dangerous. The problem with post traumatic stress disorder is that people can’t forget. They can’t let traumatic memories go. The question is why. And we don’t have an answer yet.

More on Stress

Kelly McGonigal explains "How to Transform Stress into Courage and Connection."

Robert Sapolsky explores the psychology of stress .

Jeremy Adam Smith explains the relationship between stress and empathy .

How stressed are you? Take the quiz !

PJ: Can you offer any helpful strategies to ensure that stress is beneficial rather than harmful?

DK: If you tend to have a positive attitude—a self-confident sense that you can get through a rough period—you’re more likely to have a healthy response than if you perceive stress as catastrophic. Another powerful factor is social support . If you have friends and family you can turn to during a stressful period, you’re more likely to handle the stress well. Social support buffers stress. That’s something most of us know intuitively. Now we’re beginning to understand it biologically. Researchers have identified a hormone called oxytocin that reduces the stress response. According to psychologist Kelly McGonigal , oxytocin is enhanced by social contact and support.

Another powerful buffer for stress is physical exercise. We see the evidence in animal studies. Rodents that are allowed to run are more likely to create new brain cells in response to stress than sedentary animals. I think the same thing may work for people. People who are active respond better when stress comes along than people who are inactive. Physical activity after a stressful experience also helps moderate the effects of stress.

PJ: What do you do when your own life gets stressful?

DK: I’m not the best role model. I’ll find myself writing grant proposals at one in the morning, totally stressed out. I know what I should do. Before I became a scientist, I trained as a yoga instructor. I know I should take a yoga break. But I guess it helps to know from my research that stress can be beneficial, so at least I have a positive attitude. And that plays a big role in helping people handle stress in a healthy way.

About the Author

Peter jaret.

Peter Jaret is the author of several health-related books, including In Self-Defense: The Human Immune System , Nurse: A World of Care , and Impact: On the Frontlines of Public Health . A frequent contributor to National Geographic, The New York Times, Reader’s Digest, Health magazine, More, AARP Bulletin , and dozens of other periodicals, Jaret is the recipient of an American Medical Association award for journalism and two James Beard awards. He lives in Petaluma, California.

This is how stress affects every organ in our bodies

Mental health is connected to physical well-being Image:  Unsplash/Robina Weermeijer

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• Mental health is a global crisis with half the world’s population developing a mental disorder in their lifetime.
• Our minds and bodies are deeply interlinked, so caring for them as a joint priority is vital to our overall well-being, says Dr Ruma Bhargava, the World Economic Forum’s Global Health Executive.
• Mental Health Awareness Month highlights how looking after our bodies directly helps us look after our minds.

Have you ever felt stressed and then noticed butterflies in your stomach? Or felt anxious and noticed your heart pounding harder in your chest? Well, you are not alone, as every single one of the more than 8 billion people on the planet likely has too.

What we think and how we feel are the same; our mental and physical well-being are not separate entities that we control individually. Thinking of our minds and bodies “in isolation would be a mistake,” Dr Ruma Bhargava, Global Health Executive at the World Economic Forum explains ahead of Mental Health Awareness Month .

Understanding this link – fundamental to your well-being and that of everyone you know – is more important than ever. One in every two people will develop a mental health disorder in their lifetime, a large-scale Harvard study shows.

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“Stress and anxiety affect each of organ in our body. If we feel stressed, depressed or have anxiety issues, then our bodies react. We feel our temperature increase and we are not able to control our movements, for example,” Dr Bhargava says.

“Similarly, if we have physical health conditions, like diabetes, hypertension or obesity, then we have severe mental health problems.”

Understanding the bigger picture

This deep connection between our minds and bodies is not a recent discovery. The phrase “a sound mind in a sound body” was coined by a Greek philosopher more than 2,500 years ago and many historical medical theories are based around this sense of unity.

Today, the spotlight is back on how to understand and benefit from this ancient link – especially as mental health issues are on the rise.

The far-reaching negative impact of the COVID-19 pandemic and the potential geopolitical recession add to the stresses of everyday life. The same applies to climate change, with higher temperatures linked to increases in aggression and anxiety, as well as neurological diseases like Alzheimer’s .

“If we consider our immune system as an army protecting us from invaders, like bacteria and viruses, this gets weakened with mental health issues. It then makes us susceptible to most common colds and infections,” Dr Bhargava shares.

The impact affects all age groups. A study with 30-year-old men showed that heavy stress shortens their life expectancy by 2.8 years and 2.3 years for women of the same age. Such facts can motivate us to think more about how our minds and bodies can work harmoniously together to strengthen our own “army”, and live happier and healthier lives.

The more we understand this connection, the faster we can act on it. This is where collaborative efforts, such as the Forum’s Global Future Council , can help, such as developing novel public-private initiatives to shift mental health treatment.

Opening our minds at work

Ending taboos around mental health in and out of the workplace is a must, Dr Bhargava stresses. Depression and anxiety disorders cost the global economy $1 trillion every year in lost productivity, so it also makes commercial sense to improve what and how we share our feelings.

“Workplaces are the foremost setting where a person grows into an adult and where mental health should be nurtured,” says Dr Bhargava. Open communication should be “infused into the leadership”.

With more than 1.3 billion formal workers globally , the Forum’s Healthy Workforces Initiative also aims to enhance how we talk about and manage our minds and bodies at work.

How can we create more balance?

Today, more than one billion people worldwide are obese , which weakens mental and physical health. Accordingly, one cardinal rule of good mental well-being is to eat well, making sure the food on our plate is fresh, as unprocessed as possible and full of “natural colours”, Dr Bhargava says.

The effort can significantly pay off, research shows. Eating plenty of fruits can increase life expectancy by 1.4 years while eating vegetables can extend it further.

“Move away from your screens.” That is another crucial piece of advice from Dr Bhargava to keep a better balance in life. A poll revealed that British adults spend nearly 5,000 hours a year staring at screens , including phones, computers and TVs. This means a British adult will look at a screen for 34 years – nearly half of their life expectancy.

Spending at least 20 to 30 minutes immersed in a nature setting is associated with the biggest drop in cortisol , a major stress hormone. This then helps reduce heart and stomach issues, plus many other physical ailments.

Experiencing a high level of natural diversity brings mental health benefits for up to eight hours at a time. That potentially equates to 56 hours a week of feeling good in exchange for a short daily walk. Dr Bhargava says: “We have beautiful nature. Go and spend time there.”

Finally, spend time with people you love and like. Emotional intimacy is fundamental to how we mentally and physically thrive as humans; it is wired into our DNA. Being able to depend on family and friends and share your concerns while listening to theirs enhances our mood and relieves physical strain – breaking the “vicious cycle” Dr Bhargava describes.

As “owners” of our minds and bodies – each unique to us – we can leverage these three steps to help us enjoy happier and healthier futures.

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License and Republishing

World Economic Forum articles may be republished in accordance with the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License, and in accordance with our Terms of Use.

The views expressed in this article are those of the author alone and not the World Economic Forum.

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Premium Content

Can scientists ‘solve’ stress? They’re trying.

From cardiovascular disease and obesity to a weakened immune system, the side effects of stress can be life-altering. But there may be a way to prevent those outcomes.

As modern-day stress ratchets up to what feels like unbearable levels, researchers are striving to learn more about the precise mechanisms through which it affects our body and mind. The hope is that by unlocking more about how stress works physiologically, we can find ways to prevent it from permanently harming people.

Over the last five decades, scientists have established beyond doubt that persistent stress really can poison our overall health. In addition to increasing the risk of cardiovascular disease , stress plays a role in obesity and diabetes and can weaken the immune system , leaving us more vulnerable to infectious diseases. You can recover swiftly from an episode of acute stress—for example, the alarm one might feel when caught unprepared for a presentation. Chronic stress, on the other hand, is more toxic as it is an unrelenting circumstance that offers little chance for a return to normalcy. Financial strain, having a bully for a boss, and social isolation are all examples.

Today chronic stress seems to be increasing worldwide, as people grapple with rapid socioeconomic and environmental change.   A 2023 national survey by the American Psychological Association found that stress has taken a serious toll since the start of the pandemic , with the incidence of chronic illnesses and mental health problems going up significantly, especially among those ages 35 to 44.

( Do you have chronic stress? Look for these signs. )

So far, one of the major realizations among scientists is that stress harms all of us in different and powerful ways. But is there any way to avoid it—or at least recover more quickly? Some promising avenues of research offer hope for the future.

Preventing chronic stress from harming you in the first place

Groundbreaking studies in orphans showed how stress in early life can leave an indelible mark on the brain.

For Hungry Minds

“Chronic stress in early life has more serious and lasting effects, because that’s when a lot of connections are being laid down in the brain,” says Aniko Korosi, a researcher at the University of Amsterdam who has been conducting experiments on mice to elucidate that link between early-life stress and brain development.

Korosi may have found a surprising link between stress and the resulting nutrient composition in the brain . She and her colleagues noticed that mouse pups that had been exposed to stress in the first week of their lives—having been moved from their mother’s care to a cage—had lower levels of certain fatty acids and amino acids in their brains compared with pups being raised in a stress-free environment.

She wondered if it was possible to normalize a stressed pup’s development by feeding it a diet rich in the specific nutrients its brain would be lacking. To find out, the researchers first fed a supplemented diet to the mothers so it would pass through their milk, then continued to provide it in the pups’ feed for two weeks after they were weaned. A few months later, the researchers tested the now adult mice in learning and memory. Unlike stressed mice that had never received an enriched diet, these mice did not display cognitive impairments.

( How wild animals cope with stress—from overeating to sleepless nights. )

“I was surprised that changing the nutrition could have such a powerful effect, because it’s such an easy intervention,” Korosi says.

If further studies provide more evidence of the nutritional pathway, she says, there would be a strong basis for supplementing the diets of infants born to mothers living in stressful conditions.

Developing an early warning system for stress

Katie McLaughlin, a psychologist at the University of Oregon, is investigating how mental health problems arise in adolescents as they’re going through a particularly vulnerable time in their lives, transitioning to adulthood.

She and her colleagues are still collecting data , but a smaller, precursor study tracking 30 teenagers offers clues about what the researchers might learn—and how it might help them identify stress before it goes too far.  

In that study, McLaughlin found that the extent of stress experienced by a subject in the month before their lab visit changed how their brain responded to emotionally impactful information such as when they were shown a picture of a threatening face. The brain’s prefrontal cortex, which helps regulate emotions, showed less activation when the subject had experienced higher levels of stress.

McLaughlin is optimistic that data from the ongoing study will help pinpoint changes in behavior as well as brain activity that predict the emergence of mental health problems like anxiety and depression. This could enable the development of targeted interventions delivered to teenagers at just the right time, she says. If the identified marker of stress were a sudden decrease in sleep duration or a sharp decline in social interactions, for example, it would be possible to push the intervention out to the individual on their smartphone.

“Like, here’s a reminder about good sleep hygiene, or this might be a good time to check in with your counselor at school about what’s been going on in your life,” McLaughlin explains.

( ‘Hysterical strength’? Fight or flight? This is how your body reacts to extreme stress. )

Learn more about stress and how to manage it

Preventing inflammation caused by chronic stress.

Gaining a deeper understanding of how stress affects the immune system may also help find a way to reverse those effects.

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How to cope with stress at work—and avoid burning out

In the 1980s, psychologist Janice Kiecolt-Glaser and her virologist husband, Ronald Glaser, began exploring the physiological impact of stress on two notably stressed segments of society: medical students and older caregivers. The researchers found the students’ immune systems were less robust when they were taking exams than during non-exam times—and that stress altered the body’s response to vaccines.

Researchers then administered the flu and pneumonia vaccines to individuals responsible for a spouse with dementia. Unlike medical students taking exams, who were likely stressed only in the short term, these people were experiencing unrelenting stress. When tested at set periods after inoculation, they had fewer antibodies compared with a control group —they couldn’t maintain their protective response. “That gave us good evidence that the changes brought on by stress were biologically meaningful,” says Kiecolt-Glaser, now an emeritus professor at the Ohio State University.

Around the same time, researchers led by Sheldon Cohen, now emeritus professor of psychology at Carnegie Mellon University, delivered cold-causing viruses into the nostrils of about 400 adult volunteers in the U.K. “The more stress they reported prior to our exposing them to a virus, the higher the risk was for them to develop a cold,” says Cohen. The duration and type of stress mattered: Chronic economic or interpersonal stress were what really put people at high risk—and the longer it went on, the greater the susceptibility to falling sick.

Cohen and his colleagues also learned that when exposed to viruses, chronically stressed people tended to produce an excess of cytokines—proteins that serve as messengers of the immune system, traveling to sites of infection and injury and activating inflammation and other cellular processes to protect the body. Too many cytokines cause an excess of inflammation.

Researchers still don’t know enough about how stress alters the immune system’s ability to regulate cytokines to devise an intervention to reduce the inflammation, but in one way, these findings signal some hope: There are clear targets for more work to be done.  

Understanding stress on a cellular level

The future of understanding and combating stress may lie in our DNA.

In 2023, Ursula Beattie, then a doctoral student at Tufts University, and her colleagues found possible evidence that stress can overwhelm DNA’s repair mechanisms . In their study, researchers repeatedly tapped on sparrow cages with pens, played the radio loudly, and other actions designed to cause distress but no physical harm. Blood and tissue samples from the sparrows after three weeks of this unpleasant treatment revealed damage to the DNA. “It’s like if you had two pieces of string coiled up, just like DNA, and you took a pair of scissors and cut them,” Beattie says.

While these kinds of double-strand breaks in DNA occur all the time in sparrows and other species, including humans, the damage is typically reversed through self-repair mechanisms. In a chronic-stress setting, “those repair mechanisms get overwhelmed, which is how we see a buildup of DNA damage,” Beattie explains. The damage in the birds appears to be the most severe in cells of the liver, she adds, suggesting that for humans, too, the extent and type of damage inflicted by stress might be different for different tissues of the body.

Separately, Kiecolt-Glaser and psychologist Lisa Christian at OSU are conducting a longitudinal study to determine whether chronic stress ages you more quickly. If results support a smaller, earlier study, it appears that chronically stressed caregivers not only are more likely to get sick and heal more slowly but they also show signs of accelerated aging.

We’re still learning how deep stress goes into our bodies. But these exploratory findings mean we’re getting closer to solving the puzzle that is stress, which promises a future where we can better meet the ongoing demand for change.

( 20 stress-relief gifts for the frazzled friend in your life. )

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Scientists Explained: The Link Between Stress and Digestive Health

I n the intricate web of the human body, the relationship between stress and digestive health is a complex and fascinating one. While it’s widely recognized that stress can impact various aspects of physical and mental well-being, its effects on the digestive system are often underestimated or overlooked. However, scientific research has shed light on the profound connection between stress and digestive health, revealing how stress can influence everything from gastrointestinal function to the composition of the gut microbiome. In this comprehensive exploration, we’ll delve into the latest findings from scientists, uncovering the mechanisms behind the stress-digestive connection and examining strategies for maintaining optimal digestive health in the face of stress.

Part 1: Understanding Stress and Its Impact on the Body

Before we delve into the specifics of how stress affects the digestive system, it’s essential to understand what stress is and how it manifests in the body. Stress is the body’s natural response to perceived threats or challenges, triggering a cascade of physiological changes designed to help us cope with the situation. When faced with a stressor, whether physical, emotional, or psychological, the body releases hormones such as cortisol and adrenaline, initiating the “fight or flight” response.

• The Fight or Flight Response : The fight or flight response is an evolutionary adaptation that prepares the body to either confront the threat head-on or flee from it. In response to stress, the sympathetic nervous system is activated, leading to increased heart rate, elevated blood pressure, and heightened alertness—all of which are designed to help us respond effectively to the perceived danger.
• Chronic Stress and Its Consequences : While the fight or flight response is beneficial in the short term, chronic or prolonged stress can have detrimental effects on health. Chronic stress has been linked to a range of health problems, including cardiovascular disease, immune dysfunction, mood disorders, and digestive issues. When the body is constantly in a state of heightened arousal, it can lead to dysregulation of various physiological systems, including the digestive system.

Part 2: The Gut-Brain Axis: A Two-Way Communication System

At the heart of the stress-digestive connection lies the gut-brain axis, a complex bidirectional communication system that links the central nervous system (CNS) with the enteric nervous system (ENS) of the gut. This intricate network of communication pathways allows the brain and the gut to communicate and influence each other’s function, playing a crucial role in regulating digestion, mood, and overall health.

• The Role of the Enteric Nervous System : Often referred to as the “second brain,” the enteric nervous system is a complex network of neurons located within the walls of the gastrointestinal tract. The ENS controls various digestive processes, including peristalsis, secretion of digestive enzymes, and absorption of nutrients, largely independent of the central nervous system.
• Impact of Stress on Gut Function : Stress can disrupt the delicate balance of the gut-brain axis, affecting gastrointestinal motility, secretion of digestive juices, and gut barrier function. In response to stress, the sympathetic nervous system becomes overactivated, leading to changes in blood flow to the digestive organs and alterations in gut microbiota composition.

Part 3: Stress and Digestive Disorders: Exploring the Links

Numerous studies have documented the association between stress and various digestive disorders, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastroesophageal reflux disease (GERD), and functional dyspepsia. While stress may not directly cause these conditions, it can exacerbate symptoms and contribute to disease progression through its effects on gut function and immune response.

• Irritable Bowel Syndrome (IBS) : IBS is a common gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, diarrhea, and constipation. Stress is known to trigger or exacerbate symptoms in many individuals with IBS, leading to increased gut sensitivity and altered bowel habits.
• Inflammatory Bowel Disease (IBD) : IBD, which includes conditions such as Crohn’s disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. While the exact cause of IBD remains unknown, stress has been implicated as a potential trigger for disease flares and symptom exacerbations in some individuals.
• Gastroesophageal Reflux Disease (GERD) : GERD is a chronic condition characterized by the reflux of stomach acid into the esophagus, causing symptoms such as heartburn, chest pain, and difficulty swallowing. Stress can exacerbate GERD symptoms by increasing esophageal sensitivity and altering esophageal motility.

Part 4: Strategies for Managing Stress and Promoting Digestive Health

While the link between stress and digestive health is undeniable, there are steps you can take to mitigate the effects of stress on your gastrointestinal system and promote overall digestive wellness.

• Stress Management Techniques : Incorporate stress-reduction techniques into your daily routine, such as mindfulness meditation, deep breathing exercises, yoga, or progressive muscle relaxation. These practices can help activate the body’s relaxation response, counteracting the effects of stress on the digestive system.
• Healthy Lifestyle Habits : Adopting a healthy lifestyle can support both stress management and digestive health. Prioritize regular exercise, adequate sleep, and a balanced diet rich in fiber, fruits, vegetables, and probiotic-rich foods to nourish your body and support optimal digestive function.
• Mindful Eating Practices : Practice mindful eating to promote better digestion and reduce stress-related eating. Slow down, savor each bite, and pay attention to hunger and fullness cues to avoid overeating and improve satisfaction with meals.
• Seek Professional Support : If you’re struggling with chronic stress or digestive issues, don’t hesitate to seek support from healthcare professionals such as a therapist, gastroenterologist, or registered dietitian. They can provide personalized guidance and interventions to help you manage stress, alleviate symptoms, and optimize digestive health.

In the intricate dance between stress and digestive health, fostering a balanced mind-body connection is key to promoting overall wellness. By understanding the link between stress and digestive function and implementing strategies to manage stress effectively, you can support your gastrointestinal health and cultivate a greater sense of well-being. Remember that taking care of your mental and emotional health is just as important as caring for your physical body, and prioritizing both can lead to a happier, healthier life.

Many of us can’t imagine starting the day without a cup of coffee. One reason may be that it supplies us with a jolt of caffeine, a mild stimulant to the central nervous system that quickly boosts our alertness and energy levels. [1] Of course, coffee is not the only caffeine-containing beverage. Read on to learn more about sources of caffeine, and a review of the research on this stimulant and health.

Absorption and Metabolism of Caffeine

The chemical name for the bitter white powder known as caffeine is 1,3,7 trimethylxanthine. Caffeine is absorbed within about 45 minutes after consuming, and peaks in the blood anywhere from 15 minutes to 2 hours. [2] Caffeine in beverages such as coffee, tea, and soda is quickly absorbed in the gut and dissolves in both the body’s water and fat molecules. It is able to cross into the brain. Food or food components, such as fibers, in the gut can delay how quickly caffeine in the blood peaks. Therefore, drinking your morning coffee on an empty stomach might give you a quicker energy boost than if you drank it while eating breakfast.

Caffeine is broken down mainly in the liver. It can remain in the blood anywhere from 1.5 to 9.5 hours, depending on various factors. [2] Smoking speeds up the breakdown of caffeine, whereas pregnancy and oral contraceptives can slow the breakdown. During the third trimester of pregnancy, caffeine can remain in the body for up to 15 hours. [3]

People often develop a “caffeine tolerance” when taken regularly, which can reduce its stimulant effects unless a higher amount is consumed. When suddenly stopping all caffeine, withdrawal symptoms often follow such as irritability, headache, agitation, depressed mood, and fatigue. The symptoms are strongest within a few days after stopping caffeine, but tend to subside after about one week. [3] Tapering  the amount gradually may help to reduce side effects.

Sources of Caffeine

Caffeine is naturally found in the fruit, leaves, and beans of coffee , cacao, and guarana plants. It is also added to beverages and supplements. There is a risk of drinking excess amounts of caffeinated beverages like soda and energy drinks because they are taken chilled and are easy to digest quickly in large quantities.

• Coffee. 1 cup or 8 ounces of brewed coffee contains about 95 mg caffeine. The same amount of instant coffee contains about 60 mg caffeine. Decaffeinated coffee contains about 4 mg of caffeine. Learn more about coffee .
• Espresso. 1 shot or 1.5 ounces contains about 65 mg caffeine.
• Tea. 1 cup of black tea contains about 47 mg caffeine. Green tea contains about 28 mg. Decaffeinated tea contains 2 mg, and herbal tea contains none. Learn more about tea .
• Soda. A 12-ounce can of regular or diet dark cola contains about 40 mg caffeine. The same amount of Mountain Dew contains 55 mg caffeine.
• Chocolate (cacao) . 1 ounce of dark chocolate contains about 24 mg caffeine, whereas milk chocolate contains one-quarter of that amount.
• Guarana. This is a seed from a South American plant that is processed as an extract in foods, energy drinks, and energy supplements. Guarana seeds contain about four times the amount of caffeine as that found in coffee beans. [4] Some drinks containing extracts of these seeds can contain up to 125 mg caffeine per serving.
• Energy drinks. 1 cup or 8 ounces of an energy drink contains about 85 mg caffeine. However the standard energy drink serving is 16 ounces, which doubles the caffeine to 170 mg. Energy shots are much more concentrated than the drinks; a small 2 ounce shot contains about 200 mg caffeine. Learn more about energy drinks .
• Supplements. Caffeine supplements contain about 200 mg per tablet, or the amount in 2 cups of brewed coffee.

Recommended Amounts

In the U.S., adults consume an average of 135 mg of caffeine daily, or the amount in 1.5 cups of coffee (1 cup = 8 ounces). [5] The U.S. Food and Drug Administration considers 400 milligrams (about 4 cups brewed coffee) a safe amount of caffeine for healthy adults to consume daily. However, pregnant women should limit their caffeine intake to 200 mg a day (about 2 cups brewed coffee), according to the American College of Obstetricians and Gynecologists.

The American Academy of Pediatrics suggests that children under age 12 should not consume any food or beverages with caffeine. For adolescents 12 and older, caffeine intake should be limited to no more than 100 mg daily. This is the amount in two or three 12-ounce cans of cola soda.

Caffeine and Health

Caffeine is associated with several health conditions. People have different tolerances and responses to caffeine, partly due to genetic differences. Consuming caffeine regularly, such as drinking a cup of coffee every day, can promote caffeine tolerance in some people so that the side effects from caffeine may decrease over time. Although we tend to associate caffeine most often with coffee or tea, the research below focuses mainly on the health effects of caffeine itself. Visit our features on coffee , tea , and energy drinks for more health information related to those beverages.

Caffeine can block the effects of the hormone adenosine, which is responsible for deep sleep . Caffeine binds to adenosine receptors in the brain, which not only lowers adenosine levels but also increases or decreases other hormones that affect sleep, including dopamine, serotonin, norepinephrine, and GABA. [2] Levels of melatonin, another hormone promoting sleep, can drop in the presence of caffeine as both are metabolized in the liver. Caffeine intake later in the day close to bedtime can interfere with good sleep quality. Although developing a caffeine tolerance by taking caffeine regularly over time may lower its disruptive effects, [1] those who have trouble sleeping may consider minimizing caffeine intake later in the day and before going to bed.

In sensitive individuals, caffeine can increase anxiety at doses of 400 mg or more a day (about 4 cups of brewed coffee). High amounts of caffeine may cause nervousness and speed up heart rate, symptoms that are also felt during an anxiety attack. Those who have an underlying anxiety or panic disorder are especially at risk of overstimulation when overloading on caffeine.

Caffeine stimulates the heart, increases blood flow, and increases blood pressure temporarily, particularly in people who do not usually consume caffeine. However, strong negative effects of caffeine on blood pressure have not been found in clinical trials, even in people with hypertension, and cohort studies have not found that coffee drinking is associated with a higher risk of hypertension. Studies also do not show an association of caffeine intake and atrial fibrillation (abnormal heart beat), heart disease , or stroke. [3]

Caffeine is often added to weight loss supplements to help “burn calories.” There is no evidence that caffeine causes significant weight loss. It may help to boost energy if one is feeling fatigued from restricting caloric intake, and may reduce appetite temporarily. Caffeine stimulates the sympathetic nervous system, which plays a role in suppressing hunger, enhancing satiety, and increasing the breakdown of fat cells to be used for energy. [6] Cohort studies following large groups of people suggest that a higher caffeine intake is associated with slightly lower rates of weight gain in the long term. [3] However, a fairly large amount of caffeine (equivalent to 6 cups of coffee a day) may be needed to achieve a modest increase in calorie “burn.” Additional calories obtained from cream, milk, or sweetener added to a caffeinated beverage like coffee or tea can easily negate any calorie deficit caused by caffeine.

Caffeine can cross the placenta, and both mother and fetus metabolize caffeine slowly. A high intake of caffeine by the mother can lead to prolonged high caffeine blood levels in the fetus. Reduced blood flow and oxygen levels may result, increasing the risk of miscarriage and low birth weight. [3] However, lower intakes of caffeine have not been found harmful during pregnancy when limiting intakes to no more than 200 mg a day. A review of controlled clinical studies found that caffeine intake, whether low, medium, or high doses, did not appear to increase the risk of infertility. [7]

Most studies on liver disease and caffeine have specifically examined coffee intake. Caffeinated coffee intake is associated with a lower risk of liver cancer, fibrosis, and cirrhosis. Caffeine may prevent the fibrosis (scarring) of liver tissue by blocking adenosine, which is responsible for the production of collagen that is used to build scar tissue. [3]

Studies have shown that higher coffee consumption is associated with a lower risk of gallstones. [8] Decaffeinated coffee does not show as strong a connection as caffeinated coffee. Therefore, it is likely that caffeine contributes significantly to this protective effect. The gallbladder is an organ that produces bile to help break down fats; consuming a very high fat diet requires more bile, which can strain the gallbladder and increase the risk of gallstones. It is believed that caffeine may help to stimulate contractions in the gallbladder and increase the secretion of cholecystokinin, a hormone that speeds the digestion of fats.

Caffeine may protect against Parkinson’s disease. Animal studies show a protective effect of caffeine from deterioration in the brain. [3] Prospective cohort studies show a strong association of people with higher caffeine intakes and a lower risk of developing Parkinson’s disease. [9]

Caffeine has a similar action to the medication theophylline, which is sometimes prescribed to treat asthma. They both relax the smooth muscles of the lungs and open up bronchial tubes, which can improve breathing. The optimal amount of caffeine needs more study, but the trials reviewed revealed that even a lower caffeine dose of 5 mg/kg of body weight showed benefit over a placebo. [10] Caffeine has also been used to treat breathing difficulties in premature infants. [3]

Caffeine stimulates the release of a stress hormone called epinephrine, which causes liver and muscle tissue to release its stored glucose into the bloodstream, temporarily raising blood glucose levels. However, regular caffeine intake is not associated with an increased risk of diabetes . In fact, cohort studies show that regular coffee intake is associated with a lower risk of type 2 diabetes , though the effect may be from the coffee plant compounds rather than caffeine itself, as decaffeinated coffee shows a similar protective effect. [3] Other observational studies suggest that caffeine may protect and preserve the function of beta cells in the pancreas, which are responsible for secreting insulin. [11]

Signs of Toxicity

Caffeine toxicity has been observed with intakes of 1.2 grams or more in one dose. Consuming 10-14 grams at one time is believed to be fatal. Caffeine intake up to 10 grams has caused convulsions and vomiting, but recovery is possible in about 6 hours. Side effects at lower doses of 1 gram include restlessness, irritability, nervousness, vomiting, rapid heart rate, and tremors.

Toxicity is generally not seen when drinking caffeinated beverages because a very large amount would need to be taken within a few hours to reach a toxic level (10 gm of caffeine is equal to about 100 cups of brewed coffee). Dangerous blood levels are more often seen with overuse of caffeine pills or tablets. [3]

Did You Know?

• Caffeine is not just found in food and beverages but in various medications. It is often added to analgesics (pain relievers) to provide faster and more effective relief from pain and headaches. Headache or migraine pain is accompanied by enlarged inflamed blood vessels; caffeine has the opposite effect of reducing inflammation and narrowing blood vessels, which may relieve the pain.
• Caffeine can interact with various medications. It can cause your body to break down a medication too quickly so that it loses its effectiveness. It can cause a dangerously fast heart beat and high blood pressure if taken with other stimulant medications. Sometimes a medication can slow the metabolism of caffeine in the body, which may increase the risk of jitteriness and irritability, especially if one tends to drink several caffeinated drinks throughout the day. If you drink caffeinated beverages daily, talk with your doctor about potential interactions when starting a new medication.

Energy Drinks

• Clark I, Landolt HP. Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep medicine reviews . 2017 Feb 1;31:70-8. *Disclosure: some of HPL’s research has been supported by Novartis Foundation for Medical-Biological Research.
• Institute of Medicine (US) Committee on Military Nutrition Research. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington (DC): National Academies Press (US); 2001. 2, Pharmacology of Caffeine. Available from: https://www.ncbi.nlm.nih.gov/books/NBK223808/
• van Dam RM, Hu FB, Willett WC. Coffee, Caffeine, and Health.  NEJM .  2020 Jul 23; 383:369-378
• Moustakas D, Mezzio M, Rodriguez BR, Constable MA, Mulligan ME, Voura EB. Guarana provides additional stimulation over caffeine alone in the planarian model. PLoS One . 2015 Apr 16;10(4):e0123310.
• Drewnowski A, Rehm CD. Sources of caffeine in diets of US children and adults: trends by beverage type and purchase location. Nutrients . 2016 Mar;8(3):154.
• Harpaz E, Tamir S, Weinstein A, Weinstein Y. The effect of caffeine on energy balance. Journal of basic and clinical physiology and pharmacolog y. 2017 Jan 1;28(1):1-0.
• Bu FL, Feng X, Yang XY, Ren J, Cao HJ. Relationship between caffeine intake and infertility: a systematic review of controlled clinical studies.  BMC Womens Health . 2020;20(1):125.
• Zhang YP, Li WQ, Sun YL, Zhu RT, Wang WJ. Systematic review with meta‐analysis: coffee consumption and the risk of gallstone disease. Alimentary pharmacology & therapeutics . 2015 Sep;42(6):637-48.
• Hong CT, Chan L, Bai CH. The Effect of Caffeine on the Risk and Progression of Parkinson’s Disease: A Meta-Analysis. Nutrients . 2020 Jun;12(6):1860.
• Welsh EJ, Bara A, Barley E, Cates CJ. Caffeine for asthma.  Cochrane Database Syst Rev . 2010;2010(1):CD001112.
• Lee S, Min JY, Min KB. Caffeine and Caffeine Metabolites in Relation to Insulin Resistance and Beta Cell Function in US Adults. Nutrients . 2020 Jun;12(6):1783.

Last reviewed July 2020

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