Cortisol may be the most famous hormone in wellness culture. Probably also the most misunderstood. Scroll through any health feed and you'll find claims that cortisol is making you fat, wrecking your sleep, destroying your gut, and accelerating aging. The solutions offered range from ashwagandha supplements to "cortisol face" TikTok routines to expensive "adrenal fatigue" protocols.
Some of this is directionally correct. Some of it is nonsense. And nearly all of it oversimplifies a system that is genuinely complex. One that a standard blood test captures poorly, that a single number cannot represent, and that the medical establishment and the wellness industry have each gotten partially wrong for different reasons.
This article attempts to get it right: what cortisol is, how the stress-response system actually works, why conventional testing falls short, what the research actually shows about chronic stress and health outcomes, and which biomarkers, measured properly, give you real information.
Cortisol isn't the villain wellness culture makes it. It's essential for life. Without adequate cortisol, you'd struggle to wake up in the morning, regulate blood pressure, mobilize energy, control inflammation, or respond to any physical or psychological challenge.
The system that produces cortisol is the hypothalamic-pituitary-adrenal (HPA) axis. A three-stage hormonal cascade: [1]
Step 1: The hypothalamus (a brain structure) detects a stressor and releases corticotropin-releasing hormone (CRH).
Step 2: CRH stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream.
Step 3: ACTH reaches the adrenal glands (small organs sitting atop each kidney), which respond by producing cortisol and other adrenal hormones, including DHEA-S.
Once cortisol rises sufficiently, it signals back to the hypothalamus and pituitary to stop producing CRH and ACTH. A negative feedback loop that prevents runaway cortisol production. This system is elegant when functioning properly. The problems begin when it's activated chronically, when its rhythms are disrupted, or when the feedback loop becomes dysregulated.
Cortisol isn't meant to be constant. In a healthy individual, it follows a pronounced diurnal (daily) rhythm: [2]
Cortisol is lowest around midnight. It begins rising in the second half of the night. Within 30–45 minutes of waking, there's a sharp spike called the cortisol awakening response (CAR) — typically a 50–150% increase from waking levels. [3] Cortisol then declines steadily throughout the day, reaching its nadir by bedtime.
This rhythm isn't random. The morning spike helps mobilize energy, sharpen cognition, and prepare you for the demands of the day. The evening decline is essential for melatonin production, sleep onset, and overnight repair processes. The slope of the decline — from morning peak to bedtime low — is one of the most clinically meaningful cortisol measures. [4]
And this is precisely why a single blood test is so inadequate.
Here's a fact that most people — and many wellness practitioners — don't appreciate: a single morning serum cortisol measurement has a between-visit reliability of just 0.18–0.47. [5] That means if you take the same test under the same conditions two weeks apart, the results may differ dramatically. For context, a reliability below 0.50 is generally considered poor for clinical use.
Why so unreliable? Because cortisol is:
Pulsatile. It's released in bursts, not steadily. A blood draw might catch a peak or a trough of the same underlying rhythm.
Acutely reactive. The stress of the blood draw itself — the needle, the clinical environment, the anxiety of waiting — can elevate cortisol. This is well-documented and essentially corrupts the measurement.
Time-dependent. A cortisol level at 7:30 AM means something completely different from a cortisol level at 7:45 AM, especially during the cortisol awakening response.
Influenced by dozens of variables. Sleep quality the night before, meal timing, exercise, caffeine intake, oral contraceptives, shift work, acute illness, and even the season can all shift cortisol levels significantly.
A single serum cortisol value tells you whether you might have Addison's disease (severely low cortisol) or Cushing's syndrome (severely high cortisol) — both rare endocrine conditions. It tells you almost nothing about the chronic stress-related cortisol dysregulation that actually affects most people.
By comparison, the diurnal salivary cortisol curve — multiple samples collected from waking to bedtime — has a between-visit reliability of 0.63–0.84. [5] Late-evening salivary cortisol alone reaches 0.78 reliability. These are the measurements that have been linked to actual health outcomes in major cohort studies.
Cortisol is just one piece of the stress picture.Aniva measures cortisol, DHEA-S, hs-CRP, fasting glucose, HbA1c, and magnesium — because chronic stress is a metabolic event, not just a feeling. 140+ biomarkers. One blood draw.
Let's address the elephant in the wellness room.
"Adrenal fatigue" is a term used by some alternative practitioners to describe a constellation of symptoms — fatigue, poor sleep, brain fog, salt/sugar cravings, needing caffeine to function — supposedly caused by adrenal glands that are "worn out" from chronic stress and can no longer produce adequate cortisol.
No endocrinology society recognises adrenal fatigue as a medical condition. [6] The Endocrine Society has explicitly warned that it is not a real diagnosis. A 2016 systematic review by Cadegiani and Kater in BMC Endocrine Disorders evaluated every available study on the relationship between fatigue states and adrenal function and concluded that the evidence for "adrenal fatigue" was contradictory and methodologically flawed. The authors stated plainly that there is no substantiation for adrenal fatigue as a medical condition. [7]
The three core problems with the adrenal fatigue model: [8]
First, many people with the alleged "adrenal fatigue" don't actually have low cortisol. Their salivary free cortisol may test low, but total cortisol production — including cortisol metabolites — is often normal or even elevated.
Second, even when cortisol is low, it's rarely because the adrenal glands are "fatigued." The adrenals don't wear out from overuse. Cortisol production is governed primarily by the brain and central nervous system, not by adrenal capacity.
Third, the concept is based on an outdated model (Selye's General Adaptation Syndrome) that predicts progressive adrenal exhaustion from chronic stress. Modern endocrinology has largely moved past this model.
Here's where conventional medicine and the wellness industry both get something wrong. Conventional medicine tends to dismiss adrenal fatigue and offer nothing in its place — leaving patients with real, debilitating symptoms and no diagnosis. The wellness industry fills that vacuum with an invalid diagnosis, but at least acknowledges the symptoms.
The more accurate framework is HPA axis dysregulation (sometimes called HPA-D or HPA axis dysfunction). [1] This term describes what actually happens under chronic stress: the HPA axis doesn't break — it maladapts. Think of it as a thermostat that becomes miscalibrated rather than a battery that runs out. [8]
HPA axis dysregulation can manifest as: [1] [9]
These patterns have been documented in people with chronic fatigue syndrome, fibromyalgia, PTSD, burnout, depression, and various affective disorders. [9] They're real, measurable, and clinically significant. They're just not caused by "tired adrenals."
The strongest evidence linking cortisol to health outcomes comes not from single cortisol measurements but from studies of the diurnal cortisol slope — how steeply cortisol declines from morning to evening.
The Whitehall II study is a prospective cohort study of 4,047 British civil servants. Researchers measured six salivary cortisol samples across a single day (waking, +30 min, +2.5h, +8h, +12h, bedtime) and followed participants for a mean of 6.1 years. [4]
The findings were striking. Flatter slopes in cortisol decline across the day were associated with increased all-cause mortality (hazard ratio 1.30 per 1 SD reduction in slope steepness; 95% CI 1.09–1.55). This excess mortality risk was primarily driven by cardiovascular deaths, where the association was even stronger: hazard ratio 1.87 (95% CI 1.32–2.64). [4]
Critically, this association was independent of a wide range of covariates measured at the time of cortisol assessment — including BMI, smoking, socioeconomic status, and pre-existing conditions. And it was the pattern that mattered. Neither morning cortisol alone nor the cortisol awakening response predicted mortality. Only the diurnal slope did.
A 2022 German cohort study (n=1,090 from the general population) reinforced these findings. A greater diurnal cortisol peak-to-bedtime ratio — indicating a healthier, steeper decline — predicted 50% lower cardiovascular mortality (HR 0.50; CI 0.34–0.73). Elevated late-night salivary cortisol was associated with 49% higher cardiovascular mortality (HR 1.49; CI 1.13–1.97) and 24% higher stroke risk. [10]
In the CARDIA study, a flatter late-decline cortisol slope was associated with over 4-fold higher odds of developing diabetes over 10 years. A steeper cortisol awakening response was associated with lower odds of incident diabetes. [11]
A 2017 systematic review and meta-analysis published in Psychoneuroendocrinology synthesised the evidence across multiple studies and confirmed that flatter diurnal cortisol slopes were consistently associated with worse mental and physical health outcomes — including increased inflammation, higher BMI, depression, cardiovascular disease, and cancer-related mortality. [10]
The consistent finding across all these studies: it's not your cortisol level that matters most — it's your cortisol rhythm.
If cortisol represents the catabolic (breaking-down) side of the stress response, DHEA-S represents the anabolic (building-up) side. DHEA-S — dehydroepiandrosterone sulfate — is produced by the same adrenal glands that produce cortisol, but its effects are largely protective and restorative. [12]
DHEA-S serves as a precursor for both testosterone and oestrogen. It supports neurological function, immune competence, bone density, and muscle maintenance. Critically, DHEA-S appears to buffer some of the damaging effects of cortisol — particularly its neurotoxic and immunosuppressive properties. [12]
Here's what makes the cortisol-to-DHEA-S ratio particularly informative:
Cortisol levels tend to remain stable or increase with age. DHEA-S, by contrast, peaks in the mid-20s and declines steadily thereafter — by some estimates losing 10–20% per decade. [12] This means the cortisol:DHEA-S ratio naturally shifts toward cortisol dominance as you age, creating an increasingly catabolic hormonal environment.
The research implications are significant:
A higher cortisol:DHEA-S ratio has been associated with sarcopenia (age-related muscle loss) — one study found a ratio of 0.2 or above was an independent risk factor in diabetic patients over 65. [13] The ratio has been linked to cognitive decline, immune dysfunction, treatment-resistant depression, and increased infection risk in hospitalised patients. [13]
A 2025 study in Biogerontology using data from 969 individuals in the MIDUS cohort investigated cortisol, DHEA-S, and their ratio as predictors of epigenetic age acceleration — how fast you're ageing at the molecular level. The study found that the cortisol/DHEA-S ratio added predictive power to epigenetic age estimates beyond either hormone alone. [14]
Yet DHEA-S is rarely included in standard blood panels. Most people have no idea what their levels are, let alone how they relate to their cortisol.
Stress isn't just a feeling. It's measurable.Aniva measures cortisol, DHEA-S, testosterone, SHBG, hs-CRP, fasting insulin, and magnesium — because chronic stress leaves a metabolic fingerprint across your entire blood panel, not just in a single cortisol number.
Chronic stress doesn't only affect cortisol. It leaves measurable traces across multiple biomarker categories — and this is precisely why a comprehensive blood panel reveals stress-related dysfunction that a cortisol test alone cannot.
Blood sugar and insulin. Cortisol directly raises blood glucose by stimulating hepatic gluconeogenesis (glucose production in the liver) and inhibiting insulin's effect on muscle and fat tissue. Chronically elevated cortisol is associated with insulin resistance, elevated fasting glucose, higher HbA1c, and eventually type 2 diabetes. The Whitehall II study found that elevated evening cortisol predicted incident diabetes over 9 years. [11]
Inflammation. While cortisol is anti-inflammatory in the short term, chronic HPA axis dysregulation can lead to glucocorticoid resistance — where immune cells become less responsive to cortisol's anti-inflammatory signalling. The result: elevated hs-CRP and other inflammatory markers despite cortisol being present. [11]
Thyroid function. Cortisol inhibits the conversion of T4 to active T3 and can suppress TSH secretion. People under chronic stress often show a pattern of normal TSH with low-normal fT3 — a subclinical thyroid pattern that won't trigger a diagnosis but contributes to fatigue, weight gain, and brain fog.
Sex hormones. Under chronic stress, the HPA axis prioritises cortisol production at the expense of sex hormone pathways — a phenomenon sometimes called "pregnenolone steal." Elevated cortisol suppresses gonadotropin-releasing hormone (GnRH), reducing testosterone in both men and women and contributing to menstrual irregularities, low libido, and fertility problems.
Nutrient depletion. Chronic stress increases utilisation of magnesium, zinc, B vitamins, and vitamin C. Magnesium depletion is particularly consequential because magnesium deficiency itself exacerbates HPA axis dysregulation — creating a self-reinforcing cycle of stress and depletion.
Cardiovascular markers. Cortisol promotes sodium retention (raising blood pressure), increases platelet aggregation (raising thrombotic risk), and contributes to endothelial dysfunction. The Whitehall II findings on cardiovascular mortality are not surprising when you consider cortisol's direct effects on the vasculature.
This is why testing cortisol in isolation — even if done well — misses the full picture. Chronic stress is a systemic metabolic event. Its fingerprint appears across glucose metabolism, lipids, inflammation, thyroid function, sex hormones, and micronutrient status simultaneously.
Given the limitations of single-point cortisol testing, what should you actually measure — and how?
For most people (screening and optimisation):
A morning cortisol blood draw has limited standalone value but becomes meaningful when interpreted alongside DHEA-S (for the cortisol:DHEA-S ratio), hs-CRP (for inflammatory context), fasting glucose and fasting insulin (for metabolic effects), magnesium and zinc (for nutrient depletion), and thyroid markers (for downstream effects). This cross-referencing approach compensates for cortisol's variability by looking at what cortisol does rather than just what cortisol is.
For suspected HPA axis dysfunction:
The gold standard for assessing the diurnal cortisol curve is multiple salivary cortisol samples collected at waking, 30 minutes post-waking, midday, and bedtime. [5] This captures the cortisol awakening response, the diurnal slope, and evening levels — the three parameters with the strongest evidence linking cortisol to health outcomes. Some functional medicine laboratories offer this as a 4-point salivary cortisol panel (sometimes called an Adrenal Stress Index or similar).
For suspected adrenal insufficiency (the real condition):
True adrenal insufficiency (Addison's disease) or secondary adrenal insufficiency requires medical evaluation with dynamic testing — typically an ACTH stimulation test or insulin tolerance test. [7] These are clinical procedures, not at-home tests, and should be ordered by an endocrinologist if symptoms are severe (extreme fatigue, weight loss, hyperpigmentation, hypotension, lightheadedness).
A notable recent finding adds a contemporary dimension to cortisol testing. A 2024 prospective study of 96 participants at a Long COVID clinic in Rome found that long COVID patients and asymptomatic post-COVID individuals both showed reduced morning salivary cortisol, flattened diurnal variation, and elevated evening cortisol compared to healthy controls — all hallmarks of HPA axis dysregulation. [15]
Remarkably, blood cortisol levels did not differ between groups. The dysregulation was only visible in the salivary diurnal profile. Long COVID patients also had higher ACTH than asymptomatic controls, suggesting compensatory HPA activation. This study illustrates precisely why standard blood cortisol testing fails to capture clinically meaningful cortisol abnormalities — and why the pattern of cortisol across the day matters more than any single value.
Chronic stress is a metabolic event. Your blood panel should reflect that.Aniva's 140+ biomarker panel measures stress hormones, metabolic markers, inflammatory markers, thyroid function, sex hormones, and micronutrients together — because that's how chronic stress actually manifests. Not as a single number. As a pattern across your entire physiology.
Full membership: €199/year.
The research on cortisol and health outcomes points to a clear conclusion: it's the rhythm that matters, and the rhythm is modifiable.
The four primary drivers of HPA axis dysregulation, as outlined in the integrative medicine literature, are: perceived psychological stress, chronic inflammation, blood sugar dysregulation, and circadian disruption. [8] Each of these is addressable:
Circadian alignment. Consistent wake times, morning light exposure, and evening light reduction support the natural cortisol rhythm. The cortisol awakening response is influenced by light exposure during morning awakenings — sleep/wake consistency may matter more than sleep duration.
Blood sugar stability. Blood sugar dysregulation is both a consequence and a driver of HPA axis dysfunction. Cortisol raises glucose; glucose crashes trigger cortisol. Breaking this cycle through balanced meals, adequate protein, and reduced refined carbohydrate intake can reduce cortisol demand.
Inflammation reduction. Chronic inflammation activates the HPA axis. Addressing inflammatory drivers — including gut health, food sensitivities, poor sleep, and sedentary behaviour — reduces the inflammatory load that chronically stimulates cortisol production.
Stress modulation. Mindfulness, meditation, and structured relaxation have measurable effects on cortisol patterns — though the evidence is mixed on which specific practices produce the most consistent results. The key insight is that perceived stress is a major cortisol driver, and perceived stress is modifiable.
Nutrient repletion. Magnesium, zinc, B vitamins, and vitamin C are consumed at higher rates during chronic stress. Replenishing these cofactors supports both HPA axis function and the downstream systems affected by cortisol — thyroid conversion, neurotransmitter synthesis, and immune regulation.
Cortisol is essential, not inherently harmful. The problem isn't cortisol itself — it's the disruption of cortisol's rhythm under chronic stress.
"Adrenal fatigue" is not a recognised medical diagnosis. HPA axis dysregulation is a documented clinical phenomenon, supported by large cohort studies linking flattened cortisol slopes to cardiovascular mortality, diabetes, inflammation, and accelerated ageing.
A single cortisol blood test has reliability as low as 0.18. The diurnal salivary cortisol curve, measured across multiple timepoints, reaches 0.63–0.84 reliability and is the measurement actually linked to health outcomes in the Whitehall II, KORA-F3, and CARDIA studies.
DHEA-S — the counter-hormone to cortisol — declines with age while cortisol stays stable, progressively shifting the body toward a catabolic state. The cortisol:DHEA-S ratio is linked to sarcopenia, immune dysfunction, cognitive decline, and epigenetic age acceleration.
Most importantly: chronic stress is not just a psychological experience. It's a measurable metabolic event that leaves traces across glucose metabolism, inflammatory markers, thyroid function, sex hormones, and micronutrient status. Testing cortisol alone — even when done well — captures only one dimension of a systemic disturbance. A comprehensive blood panel captures the rest.
Medical disclaimer: This content is for informational purposes only and is not medical advice. If you suspect adrenal insufficiency or have severe fatigue symptoms, consult a qualified healthcare professional. True adrenal insufficiency requires medical evaluation and treatment.
