Stress and cortisol: the impact on health

In the modern world, stress is no longer experienced in response to an occasional threat, as it once was, but has become a constant part of everyday life. Statistics from 2023 reveal that 76% of workers feel moderate to high levels of stress regularly, while 74% of the general public often feel overwhelmed by stress.

It is well known that chronic stress is linked to numerous adverse health outcomes and so finding effective stress-management strategies and ways to neutralise the ill-effects of unavoidable stress are more important than ever. In this article we will discuss not only how stress affects the body and can contribute to disease, but also how to support stress levels with nutrition, supplements and lifestyle.¹

What is cortisol? ^2-4

Known as the stress hormone, cortisol is a steroid hormone produced by the adrenal glands (that sit on top of each kidney) that is released, along with DHEA and adrenaline when we are faced with a stressor. Stress is a physiological and psychological reaction that activates the ‘fight or flight’ response to increase alertness, elevate blood pressure and increase heart rate to allow the body to react quickly to a threatening stimulus.

This stress response starts with the release of corticotropin releasing factor (CRF) and vasopressin from the hypothalamus, which stimulates the production of adrenocorticotropic hormone (ACTH) from the pituitary gland.

This prompts the adrenals to release glucocorticoids, including cortisol. Glucocorticoids are then transported into the blood stream by corticosteroid binding globulin (CBG) and diffuse through cellular membranes by binding to both mineralocorticoid receptors (MR) and glucocorticoid receptors (GR).

Once cortisol has been released to an appropriate concentration, it should signal a negative feedback mechanism to the hypothalamus to stop the release of CRH. This adaptive response in the short term triggers the suppression of inflammation, mobilises energy, increases focus and activates the immune system, which can all be useful when faced with a stressful situation or threat.

Along with its role in the stress response cortisol actually has many other functions in the body such as modulating inflammation, regulating blood pressure and supporting the metabolism through regulating blood sugar levels and playing a role in how the body uses macronutrients.

It is also vital for the regulation of the circadian rhythm; cortisol peaks in the morning (called the cortisol awakening response or CAR) to give us energy to get up and get ready for the day, and then gradually declines to its lowest point at midnight to allow for a restful night’s sleep.

Cortisol is therefore an essential hormone that affects almost every organ in the body.

Persistent stress and activation of the ‘fight or flight’ response halts non-essential functions such as digestion and repair. It also causes hyperactivity of the HPA axis leading to increased cortisol release and a dysregulation of the glucocorticoid negative feedback loop, which is linked to metabolic, immune and psychiatric dysfunction.

Symptoms of disrupted cortisol levels ⁵

Chronic ongoing stress resulting in continuous activation of the HPA axis means that cortisol is constantly being drawn upon, disrupting the delicate feedback mechanism and making the body less sensitive to its effects, known as cortisol resistance. This in turn can wreak havoc to health. Disrupted cortisol levels encompass both physical and psychological symptoms and include:

• Poor sleep and insomnia ⁶
• Fatigue upon waking
• Weight gain
• Poor immunity
• Food cravings for sugar
• Low libido
• Poor digestive health
• Anxiety
• Low mood and irritability
• Depression
• Pain sensitivity ⁷
• Migraines⁸
• Irregular mensural cycles

The impact of chronically high cortisol on health

Chronic stress resulting in a dysregulation of the HPA axis and cortisol resistance has been linked to many health concerns, conditions and diseases, many of which we will discuss below;

Blood sugar management ^{2, 9-11}

In a healthy individual, cortisol works in harmony with insulin to keep blood sugar levels stable, with cortisol ensuring sufficient glucose levels and insulin helping to promote glucose uptake into the cells.

When the body is in a sympathetic nervous system state or experiencing “fight or flight”, cortisol can trigger glucogenesis in the liver (converting glycogen into glucose to be used as fuel), which promotes lipolysis in the adipocytes and inhibits insulin secretion. This means glucose is less able to enter the cells and instead stays in the blood stream, elevating blood sugar levels. Chronically high cortisol levels therefore can lead to persistent high blood sugar (hyperglycemia), promoting insulin resistance and the risk of type two diabetes. Furthermore, research has found that participants with diabetes have higher cortisol levels and increased glucocorticoid sensitivity at baseline, while other studies found that those with glucose intolerance and other features of metabolic syndrome have raised fasting cortisol concentrations. 

Weight management ¹²

Weight management and obesity is a complex and multifactorial issue with a multitude of individual differences. Research has found that there is a relationship between HPA axis activation and energy homeostasis, with findings suggesting that while not all obese individuals have high cortisol levels, stress may play a role in the development and maintenance of obesity and weight gain.

CRH, released during the stress response initially suppresses appetite, but a short while after appetite returns due to neuropeptide Y stimulation, this reduces the sensitivity of leptin and insulin, promotes insulin resistance and increases the desire for energy dense sweet and fatty foods. Furthermore, cortisol enhances gluconeogenesis and lipolysis increasing free fatty acids that promote fat storage and insulin resistance, as well as contributing to a reduction in muscle mass and an increase of visceral fat accumulation, which increases the risk of obesity and metabolic syndrome.

Elevated cortisol may also play a role in food consumption, food choice and can affect sleep quality and duration, disrupting blood sugar levels and promoting unhealthy food choices.

Thyroid  ^{13, 14}

The Hypothalamic-pituitary-thyroid axis (HPT) control thyroid hormone production. The HPT axis is slightly upregulated during acute stress, however when this becomes prolonged and chronic, there is a dampening of this axis negatively affecting thyroid hormone production. Cortisol can reduce TSH which subsequently affects T3 and T4 levels, as well as increasing the conversion of T4 to reverse T3 (rT3). rT3 can then bind to T3 receptor sites, interfering with T3 binding. Although research is mixed, high rT3 has been linked to lower mental and physical functioning with one study finding that women with stress related mental health concerns exhibited lower levels of TSH and T3.

Inflammation ^15,16

Cortisol functions to reduce inflammation in the body in the short term, hence it is used in medications for autoimmune and inflammatory disease. However, if the body’s production of cortisol is constantly elevated over time this can actually increase inflammation in the body and drive immune dysfunction.

Stress, when chronic, causes the immune system to overact and release excessive amounts of inflammatory molecules to push the body into a more inflamed state. This effects the permeability of the blood brain barrier and negatively influences the central nervous system, leading to the increased risk of neuroinflammation and subsequent conditions such as depression and anxiety. Imaging studies have found that inflammation impacts certain areas of the brain such as the amygdala, which is particularly involved in anxiety conditions.

Inflammation is bidirectionally linked to HPA dysregulation, with inflammatory mediators having a significant effect on the HPA axis and the malfunctioning of the HPA contributing to inflammation. Research has found that chronic and even acute stress can raise pro-inflammatory markers such as IL-6.

Immunity ^17-19

Chronic stress can suppress the functioning of the immune system, altering immune cells and increasing the production of proinflammatory cytokines.  Glucocorticoid hormones, catecholamines and opioids released from HPA activation can decrease the activity of cytotoxic T lymphocytes and natural killer cells. A healthy immune system has an optimal balance of Th1 and Th2 cells (T helper cells involved in cellular and humoral immunity), however glucocorticoids can modulate T cell function and cause a shift from Th1 to Th2, which is linked to autoimmunity. One study found that those with stress related disorders were associated with a higher risk of autoimmune disease compared to matched controls.

Stress mediators can pass through the blood brain barrier and can adversely affect a range of hormone receptors involved in immune function (for example growth hormone) altering immune function.

Cardiovascular ²⁰

An association between stress and the cardiovascular system is well noted with researchers finding that stress can alter heart rate, strength of contraction, blood pressure and induces the narrowing of veins. It can signal to the autonomic nervous system to increase vasoconstriction, increase blood lipids and blood pressure, inducing vascular changes and atherogenesis which can cause cardiac arrythmias and myocardial infraction.

Researchers state that even raised morning cortisol have been associated with an increased risk of cardiovascular disease and that targeting stress reduction, among other factors, is a vital strategy in reducing the risk of cardiovascular diseases.

Methylation ²¹

Stress can impair by depleting crucial B vitamins such as B12 and folate, as well as reducing adrenaline clearance produced from the stress response.  Long term exposure to stress can alter DNA methylation, and therefore gene expression, contributing to poor health and disease. Poor methylation is associated with increased levels of the waste product homocysteine which is associated with and increased risk of chronic disease including cardiovascular disease, metabolic syndrome and dementia.

Digestion ^22,23

Stress may alter food consumption, digestion and nutrient absorption as well as affecting bowel motility, mucus secretion, stomach acid levels, microbial balance, pathogenic bacteria, inflammation and intestinal permeability.

Evidence points to a bidirectional communication pathway between the gut microbiota and the neuroendocrine system, with conditions such as irritable bowel syndrome (IBS), which is seen as a stress sensitive disorder, being associated with HPA activation. Gut microbiome imbalances can lead to inflammation and HPA activation. Research has found that pro and prebiotics can not only have a beneficial effect on the health of the gut, but can also be used to support the regulation of the HPA axis.

Sleep ^24,25

The circadian rhythm, the 24-hour cycle that is part of the body’s internal clock, is very sensitive to external stressors and disturbed sleep has been found to be detrimental to mental and physical health, increasing the risk of cardiovascular disease, mood disorders, obesity, pain conditions and blood sugar imbalances. Greater daily stress is associated with shorter durations in sleep, greater trouble getting to and staying asleep and higher cortisol levels upon waking.

A typical diurnal pattern involves high cortisol upon waking with an increase 30 minutes later – called the CAR, followed by a gradual decrease, with lowest levels occurring at midnight. Chronic stress can not only impair this pattern, disrupting the sleep-wake cycle and affecting sleep, it can also have knock on effects with blood sugar management, inflammation and mood. 

Brain health ^{26, 27}

High stress levels are a risk factor for a multitude of other health conditions, including neurodegenerative diseases such as Alzheimer’s disease (AD). In addition to its complex pathophysiology, including the elevated levels of inflammatory markers and oxidative stress implicated in the disease, one of the proposed ideas is that one of the main brain areas compromised in AD, the hippocampus, also contains the highest numbers of glucocorticoid receptors, and therefore may be susceptible to chronic activation and subsequent damage.

Chronic stress and elevated cortisol may play a large role in the development of depressive disorders. Studies have found that those with major depressive disorder have higher cortisol levels compared to controls, suggesting that a dysregulation of the HPA may play a significant role in depression.

Other research has found that chronic stress can actually cause structural changes in different parts of the brain, including atrophy of the brain mass and reduction in overall brain weight, which can then alter cognition, memory and have long lasting effects on the nervous system.

How to reduce cortisol levels naturally

Reducing stress and cortisol is a lot easier said than done, in the modern world we live in, but being mindful of how stress can negatively affect health both physically and psychologically can highlight the importance of incorporating stress management techniques into your day to live a healthy life. While a great deal of everyday stress is unavoidable, there are things you can do to support yourself to be more resilient to stress and practices that can help reduce its ill effects. 

Nutrition

An anti-inflammatory diet consisting of unprocessed, wholefoods, with an abundance of fruits and vegetables, good quality protein and healthy fats should be the foundation of any healing plan to ensure adequate nutrient intake. Pro and prebiotics, including fermented foods can support stress reduction due to the intrinsic link between the gut and the brain, known as the gut-brain axis.

Certain things are known to impact cortisol levels are and best avoided including:

• Caffeine is a stimulant that can activate the HPA axis and increase levels of salivary cortisol. ²⁸ It is instead advised to opt for herbal tea, or green tea which contains L-theanine.

• Sugar can contribute to inflammation and effect glycaemic regulation by creating big fluctuations in blood sugar, with low blood sugar levels triggering cortisol release. ²⁹

Lifestyle interventions to reduce raised cortisol

Exercise ^{30, 31}

Light to moderate exercise has been shown to decrease cortisol levels and improve sleep. Research shows that regular exercise can have numerous beneficial effects on quality of life both physically and mentally, with those who maintain regular physical activity having better overall mood, self-esteem and feelings of well-being. Although exercise initially causes a short-term increase in cortisol, levels then decline, supporting the body’s resilience to physical exertion and improving the functioning of the HPA axis. It can also help to increase REM sleep and improve overall quality and help balance levels of leptin and ghrelin, modulating appetite to support blood sugar balance and weight management. Exercise even has immunomodulating effects, reducing inflammation in the body and promoting brain derived neurotrophic factor (BDNF).

Yoga ^{32, 33}

Yoga asana and mindfulness movement are popular tools for stress reduction and have been found to be associated with better sympathetic nervous system regulation as well as reduced waking and evening cortisol, reduced cholesterol, higher heart rate variability, reduced blood pressure and fasting blood glucose.

One intervention study found that healthcare professionals who attended weekly yoga classes and practiced independently had better health and well-being outcomes, scoring better on scales for mindfulness, stress and perceived stress, sleep and vitality.

Sleep ³⁴

Prioritising sleep is vital to support the immune system, cognition, blood sugar balance and mood and for the glycogenotic process of replenishing glucose storage in the neurons. Deep sleep inhibits the HPA axis and gives the body a chance to rest and repair. To support good sleep, aim to improve your sleep hygiene by avoiding screens before bed and aiming for 7-9 hours a night.

Meditation ^{35, 36}

Meditation has been shown to support psychological health by enhancing mindfulness and supporting feelings of well-being and can therefore be a helpful tool for stress reduction. Meditation has been shown to increase activity in the left anterior brain, which is associated with happiness.

Other lifestyle practices to support stress reduction and management include spending time in nature ³⁷ and breathwork, such as diaphragmatic breathing which have both been found to be effective stress management habits.³⁸ 

Supplements that can help reduce cortisol 

Magnesium ³⁹

Magnesium is involved in almost all metabolic and biochemical processes in the body and deficiency is a common complaint that can present as fatigue, anxiety, headaches and muscle tension. Research has found that magnesium is an important mineral in the central nervous system and that stress can rapidly deplete levels in the body. Low magnesium could reduce the body’s resilience to stress, creating a cycle that can contribute to deficiency. Magnesium inhibits glutamatergic transmission and promotes GABA activity while playing an indirect role in reducing the release of ACTH by having a modulating effect on neurotransmission pathways to help decrease levels of cortisol.

B vitamins ⁴⁰

B vitamins are key nutrients in supporting the nervous system and the production of energy, and are rapidly depleted in the stress response. They are also needed for the production of GABA which can in turn affects the hormonal control of cortisol.

Vitamin C ⁴¹

Vitamin C is an antioxidant that plays a role in adrenal function and has the ability to modulate monoaminergic and glutamatergic neurotransmitter systems.

L-theanine ^42-44

L- theanine is an amino acid found in green tea leaves that has been shown to have a neuroprotective effect on the brain when exposed to stress. Studies have found that L-theanine has a relaxing effect and helps to reduce the stress response by having an effect on heart rate and blood pressure, alongside increasing alpha brain waves which are associated with a relaxed calm state – much like that achieved through meditation. It can also have a mild effect on levels of neurotransmitters in the brain such as serotonin, dopamine, glycine and GABA.​

Ashwagandha ^45,46

Studies have found that ashwagandha exhibits its significant stress reducing properties via its effect on the HPA axis, sympathetic-adrenal medullary axes and through serotonergic and GABAergic pathways. Studies have found the ashwagandha root attenuated the increase in glucocorticoids cortisol and corticosterone after stress. Further exploration of the mechanisms has suggested that ashwagandha’s use in anxiety, depression and insomnia may be due to its effect on reducing oxidative stress, pro-inflammatory cytokines and neuroinflammation, while modulating the GABA receptor and supporting immune function.

Rhodiola ⁴⁷

Rhodiola is an adaptogen that has antioxidant, neuroprotective, anti-fatigue, anti-inflammatory and mood supportive effects, and is therefore a popular choice for those suffering with fatigue and ‘burnout’ from stress.

Omega-3 ^{48, 49}

Studies have found that omega-3 supplementation reduced overall cortisol levels compared to placebo. Authors theorised that omega-3 intake helped build up stress resilience by reducing the effects of elevated cortisol after a stressful experience, while other research found that supplementing omega-3 inhibited adrenal activation associated with stress.

Probiotics ⁵⁰

The evidence of the gut-brain axis signifies the important relationship between the gastrointestinal tract and the central nervous system. Probiotics are now thought to have the potential to exert psychotropic effects on depression, anxiety and stress, perhaps due to their ability to regulate neurotransmitters including GABA, serotonin and glutamate. Certain strains of Lactobacillus spp and Bifidobacterium spp such as Lactobacillus plantarum are thought to be directly involved in the production of GABA and serotonin.

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Post originally published in 2017. Now completely updated and revised.

Last updated on 31st May 2024 by cytoffice