Cortisol, a Misunderstood Hormone

Cortisol is often presented as “the stress hormone,” which isn’t wrong, but it remains a largely incomplete label. In reality, cortisol is more the hormone of change or adaptation than that of stress. Without cortisol, it would be difficult to properly maintain blood glucose between meals, modulate inflammation, or even adapt to physical exertion or an infection. The bad press this hormone receives points to the wrong culprit. The problem therefore does not come from cortisol itself, but from the context associated with its production (acute vs. chronic), the time of day, tissue sensitivity, and situations where exposure is too high (corticosteroid treatments, Cushing’s syndrome) or too low (adrenal insufficiency/Addison’s disease).

But first, let’s move on to the official introductions…

What is cortisol, where does it come from, and what is it for?

Origin: the adrenal glands and the HPA axis

Cortisol is the main glucocorticoid produced by the fasciculata zone of the adrenal cortex. Its release is controlled by the hypothalamic–pituitary–adrenal axis (often abbreviated HPA axis: hypothalamus (CRH) → pituitary gland (ACTH) → adrenals (cortisol)).

This axis functions like a thermostat: cortisol exerts negative feedback on the hypothalamus and pituitary gland, which limits runaway activation of the response¹.

What is it for?

Its functions can be summarized into three main families.

Energy and metabolism

Cortisol helps the body mobilize energy when needed: maintaining blood glucose (via hepatic glucose production), modulating the use of energy substrates, and effects on energy expenditure^2-5.

Response to stress and exertion

Faced with a stressor (psychological, infection, intense effort, sleep deprivation), cortisol contributes to adaptation. During physical efforts, an acute rise is part of a normal physiological response to demanding training or competition^3-5.

Immunity and inflammation

Cortisol is a powerful immune modulator: it tends to reduce certain productions of pro-inflammatory cytokines and contributes to a system’s return to baseline after immune activation6.

How is cortisol measured?

There is no universal measure of cortisol: the fluid and the chronology are chosen depending on the question and what one wants to observe (acute stress? circadian rhythm? chronic exposure? endocrinological diagnosis?). The methods do not always yield the same absolute values, but they often describe comparable patterns^7,8.

Blood (serum/plasma)

• Advantage: very commonly used clinically; useful for dynamic tests (ACTH stimulation, dexamethasone suppression).
• Limitation: a large proportion of circulating cortisol is bound to a protein (CBG), so total cortisol can vary with CBG (oral contraceptives, physiological states), which complicates interpretation⁹.

Saliva (salivary cortisol)

• Advantage: better reflects the biologically active free fraction; easy and repeated sampling (useful for diurnal rhythm, evening cortisol, cortisol awakening response, etc.).
• Important clinical use: late-night salivary cortisol is a sensitive tool in screening for Cushing’s syndrome^7,8,10.

Urine (urinary free cortisol, 24 h)

• Advantage: estimate of overall daily production.
• Limitation: collection constraints, variability.

Hair

• Advantage: marker of more chronic exposure (weeks/months).
• Limitation: delicate interpretation (cosmetics, hair growth, methodological heterogeneity); mainly useful in research¹¹.

What influences cortisol and its production?

Timing (circadian rhythm)

In healthy adults, cortisol follows a diurnal rhythm: peak in the morning and nadir in the evening^7,12. This rhythm is central: comparing two measurements taken at different times often makes little sense.

Sleep, shift work schedules, and light

Sleep and circadian alignment strongly influence cortisol dynamics, including its slope over the course of the day¹³. Shift work and chronic disruptions are often associated with less favorable profiles (flattened slope, relatively higher evening levels) and an increased body mass index in some cohorts¹⁴.

Psychosocial stress and mental health

Acute stress often increases cortisol transiently; in contrast, chronic stress is more often associated with changes in the profile (flattened slope, higher evening cortisol in some people) and markers of lower well-being^15,16.

Physical activity and fitness

• Acute: intense effort can cause a large rise, sometimes up to ~200% above baseline, then return to normal within a few hours^17,18.
• Adaptation: good physical fitness and prior physical activity are associated with less cortisol secreted during psychosocial stress, suggesting better regulation¹⁹.

Age, sex, body composition

• Age: average levels increase with age (reported order of magnitude: +20 to +50% between 20 and 80 years) and rhythm amplitude may decrease¹².
• Body composition: in obesity, cortisol is not necessarily higher in the blood. However, the body may produce/recycle more locally in certain organs, especially the liver and abdominal (visceral) fat. In other words, even if a blood test shows nothing abnormal, some tissues may be exposed to more cortisol locally, which more readily promotes fat storage around the abdomen and metabolic problems^20,21. In addition, obesity is often accompanied by changes in how the body converts and eliminates cortisol; cortisol can be inactivated and then reactivated later, which changes the overall balance^20,21. Diet may also have a combined impact with body composition and influence these mechanisms.

Nutrition

The literature suggests that, beyond total energy intake and weight changes, the quality of intake (macronutrient distribution) can modulate cortisol dynamics. In obese men, Stimson et al.²² notably showed that diet composition could alter cortisol metabolism independently of weight changes, reinforcing the idea that the nutritional environment directly influences the corticotropic axis and/or peripheral pathways of cortisol transformation (e.g., tissue activation/inactivation).

In parallel, some real-world studies indicate that a high intake of sugars is associated with an attenuated cortisol response after an acute physiological stressor²³. This observation fits within the “comfort foods” hypothesis, according to which eating highly palatable, sugar-rich (and more broadly energy-rich) foods could help dampen the stress response (at least in the short term), at the potential cost of reinforcing comfort-eating behaviors and a stress–diet vicious cycle.

What are the “normal” values?

In healthy adults, cortisol secretion by the adrenal cortex follows a circadian (diurnal) rhythm under control of the HPA axis. The typical profile is characterized by a high peak in the morning (around early morning, often around 08:00) followed by a gradual decline throughout the day, reaching a nadir in the evening and during the night^7,12.

In practice, reported average salivary measurements in healthy adults are about 15.5 ± 0.8 nmol/L in the morning (08:00) and 3.9 ± 0.2 nmol/L in the evening (20:00), illustrating a large gap between morning and evening7. At the individual level, baseline concentrations tend to be relatively stable from one day to the next²⁴, even though factors such as age can modulate amplitude and average level¹².

Discussing “normal ranges” without specifying the sample type (saliva/blood), time, method, and context is a classic source of confusion.

Variations between groups (trends)

Distinct profiles of cortisol production and dynamics can be observed^7,12,15,25:

• Obese adults: rhythm often preserved, but slope sometimes slightly flatter; evening cortisol sometimes higher, and tissue metabolism altered^20,25.
• Depression / comorbid anxiety: often higher evening cortisol and a flattened diurnal slope in several cohorts^15,26.
• Athletes: overall rhythm generally preserved; often less cortisol in response to certain standardized stresses, consistent with adaptation¹⁹.
• Cushing’s syndrome: loss of the normal rhythm, elevated cortisol including late at night^7,10.
• Adrenal insufficiency (Addison’s): low cortisol and insufficient response to stimulation tests⁷.

Physiological effects on health, body composition, and physical fitness

Cardiometabolic health

Unfavorable cortisol profiles (e.g., high cortisol at night, flattened diurnal slope) are associated with greater cardiometabolic risk in several observational studies: type 2 diabetes, metabolic syndrome, and cardiovascular events^27-30. It is important to understand that these are correlations for which a causal link cannot be established—meaning a daily pattern of cortisol production is not necessarily the cause of the condition or state. In this case, it is not necessarily elevated cortisol that leads to cardiometabolic disorders; rather, it may accompany other conditions or processes that have a more causal relationship.

Immunity and inflammation

When experiencing acute stress (fear, intense effort, infection, injury), the body triggers an inflammatory reaction to defend itself. Cortisol then rises and calms certain “messengers” of inflammation (pro-inflammatory cytokines), preventing the reaction from going too far.

This is what Petrovsky et al.⁶ emphasize: pro-inflammatory cytokines follow rhythms throughout the day, and cortisol contributes to their regulation (when cortisol is higher, these cytokines tend to be more “braked”).

If cortisol remains too high for too long (chronic stress, lack of sleep, disrupted circadian rhythms, etc.), or if its day/night rhythm is disturbed, the problem is that the immune system is kept under continuous “braking.”

Possible result:

• less effective immune response (poorer response to threats, slower recovery),
• inflammatory and metabolic imbalances,
• and, with age, an association with greater frailty (loss of physical reserves, increased vulnerability), as discussed by Erceg et al³¹.

Cortisol is useful for shutting down excessive inflammation in the moment, but if it is chronically high or poorly timed, it may contribute to less effective immunity and greater frailty, especially in older people. Again, one should not seek to lower cortisol to solve the problem, but rather act on the causes leading to prolonged cortisol elevation.

Body composition: fat, muscle, distribution

Chronic excess cortisol, together with a positive energy balance, promotes fat redistribution (notably visceral) and metabolic dysregulation^20-22.

On the muscle side, cortisol is catabolic. However, avoid the simplistic shortcut that “cortisol causes muscle loss.” In reality, cortisol is closely associated with muscle remodeling and enables muscle restructuring by specifically degrading less functional components³². A striking finding is that inactivity amplifies the catabolic muscle response to cortisol, linking endocrinology and behavior³³ and reinforcing the observation that an inactive muscle tends to deteriorate—not because cortisol is present, but because stimulation is absent. Cortisol acts only as a mediator of change.

The relationship with body mass index may be non-linear: some syntheses report a “U”-shaped association (higher cortisol in anorexia and severe obesity, lower in intermediate BMIs)³⁴.

Physical fitness and performance

• Acute: a transient rise during or after intense training is not “bad”: it is part of the adaptive response¹⁷.
• Chronic: if training load, lack of recovery, and stressors accumulate, an overreaching/overtraining state can be accompanied by hormonal alterations, poorer recovery, and declining performance^35,36. Again, cortisol is not the cause of reduced performance, but the mediator reflecting the imbalance between demand and recovery.

Psychological effects of cortisol

Cortisol also acts on the brain: attention, memory, learning, emotional reactivity. Here too, duration and intensity matter.

Acute stress: sometimes protective

Studies show that stress-induced increases can be associated with reduced negative affect after the event, suggesting a “buffering” role in certain contexts37. Other work describes effects on alertness and emotional state38.

Chronic stress: risk of dysregulation

Higher evening levels, a flattened diurnal slope, or chronic exposure reflected in hair are associated with indicators of lower well-being and more depressive symptoms^15,16.

Reward and motivation

Recent psychophysiology data suggest that acute stress, via increased cortisol, can reduce the neural response to reward³⁹, which offers a possible bridge to anhedonia and reduced motivation in some people exposed to repeated stress.

Distinguishing “everyday-life cortisol” from supraphysiological doses and pathological states

“Physiological” cortisol (general population)

• Varies across the day (high morning, low evening).
• Rises during intense effort or acute stress, then falls again17.
• Shows relative intra-individual stability: each person has a baseline “signature,” even though inter-individual variability is observed24.

In this framework, the goal is not to have “the lowest cortisol possible,” but a coherent rhythm and consistency between demand and recovery.

Pathological states (maladaptive exposure)

• Cushing’s syndrome (endogenous hypercortisolism): high cortisol, loss of circadian rhythm; late-night salivary cortisol is a key marker^7,10.
• Adrenal insufficiency/Addison’s (hypocortisolism): cortisol too low, inability to increase properly during stress; insufficient response to tests7.

Supraphysiological doses (corticosteroids)

Administration of glucocorticoids (e.g., high-dose or long-term hydrocortisone/prednisone) can reproduce certain hypercortisolism effects: muscle wasting, central fat gain, bone fragility, variable psychological effects. The essential nuance is that these effects often reflect sustained and “abnormally” high exposure, closer to Cushing’s than to normal fluctuations linked to a stressful day40.

Cortisol, energy expenditure, and appetite: what really changes

Cortisol influences energy balance through two main pathways: energy expenditure (what the body “burns”) and intake (hunger, appetite, food choices). The effects depend strongly on whether the elevation is acute vs. chronic, on circadian rhythm, and on context (sleep, stress, activity level, pathology).

Effects on components of energy expenditure

Resting energy expenditure (REE/RMR)

• Acute effect: increase in resting metabolism
  In healthy adults, induced acute hypercortisolemia (hydrocortisone infusion) increases resting metabolism by about +9 to +15%2. Proposed mechanisms include increased protein flux and substrate oxidation.
• Chronic effect: a less “linear” relationship in populations
  In prolonged dysregulation states, resting energy expenditure becomes difficult to interpret because it depends heavily on body composition and clinical context. For example, in anorexia nervosa (where hypercortisolism is common), resting metabolism may appear relatively high compared to body mass⁴¹. Conversely, in obesity, tissue exposure to cortisol is often modified (local metabolism), which complicates the simple link between cortisol measurement and energy metabolism²¹.

Diet-induced thermogenesis

• Modulated by nutrition and individual context
  Diet-induced thermogenesis primarily depends on meal energy and composition (e.g., fats, carbohydrates, proteins), and to a lesser extent on characteristics such as BMI and sex⁴².
• When cortisol is chronically elevated, diet-induced thermogenesis may be increased in some states
  In people with anorexia nervosa during fasting/malnutrition, energy expenditure associated with digestion is reported to be higher and correlated with hormonal markers including cortisol and ACTH⁴¹.
• In obesity: heterogeneous data
  Findings on diet-induced thermogenesis in obesity are variable and method-sensitive⁴³. One hypothesis is that differences in cortisol metabolism (not only its circulating level) may contribute to these discrepancies^20,21.

Activity-related energy expenditure

• Major indirect effect: cortisol and activity co-modulate
  Physical activity is an important determinant of changes in body composition⁴⁴. It also seems to reduce cortisol secretion during psychosocial stress: better fitness and prior activity lead to less cortisol secreted during stress¹⁹.

In other words, in “real life,” part of the cortisol–weight association may run through loops where stress/inactivity and cortisol reinforce each other.

Effects on appetite, cravings, and food choices

Cortisol does not regulate appetite alone: it interacts with other signals (sleep, perceived stress, emotions, food availability), but several observations converge.

Chronic stress, “comfort” eating, and energy density

In field studies, higher stress is associated with less favorable eating habits, with more energy-dense foods; some data also report links between stress, morning cortisol, and consumption of more energy-rich foods⁴⁵.

In parallel, a real-world study observes that higher sugar intake is associated with reduced cortisol reactivity after an acute stressor, consistent with the “comfort food” hypothesis²³.

Why does it matter?

Even if cortisol can increase certain components of energy expenditure, weight-gain trajectories associated with chronic stress often seem explained by a combination of:

• circadian dysregulation and sleep,
• less physical activity,
• more energy-dense and more irregular eating,
• and, in some people, increased tissue exposure to cortisol (local metabolism), especially at the visceral level^20,21.

High cortisol: direct cause of harmful effects, or just a “thermometer” of stressors?

The most accurate answer is: both, depending on the context. Cortisol can be a causal mediator (it actively contributes to effects), but it is also very often a marker of what is going on (chronic stress, sleep deprivation, illness, inflammation, circadian misalignment), and these factors themselves have independent harmful effects.

When cortisol is probably causal (direct effect)

This is mainly seen when exposure is strong, prolonged, or disconnected from physiological need:

• Pathological hypercortisolism (e.g., Cushing’s syndrome): loss of circadian rhythm and high cortisol day and night, with a typical clinical picture^7,10. Here, it is hard to attribute effects solely to the “stressor”: hormonal excess is central.
• Exogenous glucocorticoids (treatments): they reproduce metabolic and body effects consistent with an excess glucocorticoid signal, supporting the idea that high exposure can be harmful in itself⁴⁰.
• Plausible and demonstrated mechanisms: cortisol directly influences metabolism, muscle proteolysis, and other pathways; for example, inactivity amplifies the muscle catabolic response to cortisol³³, and elevations can increase protein flux².

When cortisol is mostly a marker

In the general population, most studies linking cortisol and health are observational: they show associations, but causality is complex.

• “At-risk” profiles (flattened diurnal slope, higher nocturnal cortisol) are associated with cardiovascular outcomes and mortality^29,46,47. However, these profiles may reflect global dysregulation related to disease, sleep, work, inflammation, or health behaviors.

The most realistic model: bidirectional loops and confounders

A key point is that relationships are often bidirectional: illness, chronic stress, or inflammation can alter cortisol, and sustained (or poorly timed) cortisol elevation can then worsen certain parameters. This “two-way” view is explicitly discussed in recent reviews on cortisol–stress–disease⁴⁸.

Practical implication: focus less on “the number” and more on context and rhythm

Rather than concluding that elevated cortisol is synonymous with danger, the data support a more nuanced interpretation:

• Acute spikes (exercise, brief stress) are generally adaptive and transient^17,18.
• What often seems most informative for risk is disruption of the rhythm (flattened slope, elevated nighttime cortisol) and chronicity, which may signal a high stress load, circadian misalignment, or an underlying condition^13,29.

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