Is Your Stress System Burned Out? The HPA Axis and Chronic Illness

Many people living with Chronic Fatigue Syndrome (ME/CFS), Long Covid, or Fibromyalgia experience overwhelming fatigue, brain fog, poor sleep, and a frustrating lack of answers. One of the most overlooked—but increasingly studied—factors behind these symptoms is dysfunction in the HPA axis, the body’s central stress-response system.

Let’s explore what the HPA axis is, how it goes wrong in chronic illness, and what the latest research says.

What Is the HPA Axis?

The Hypothalamic-Pituitary-Adrenal (HPA) axis is a communication pathway between three key parts of your body:

• Hypothalamus: your brain’s stress detector

• Pituitary gland: the middleman

• Adrenal glands: produce cortisol, your main stress hormone

  
  

When you face a stressful event, your HPA axis kicks into gear, producing cortisol to help you stay alert, manage inflammation, and keep your blood sugar stable.

But in people with chronic illness, this system may become blunted, exhausted, or dysregulated—a condition often referred to as hypocortisolism.

When the Stress System Fails: What Happens?

Normally, cortisol levels are highest in the morning (to help you wake up) and lowest at night (so you can sleep). In chronic illness, this natural rhythm often breaks down. You may feel:

• Exhausted in the morning

• Wired but tired at night

• Extra sensitive to stress or stimulation

• Prone to dizziness, blood sugar crashes, or mood swings

These symptoms often point to a dysregulated HPA axis.

HPA-Axis Dysfunction in Chronic Fatigue Syndrome (ME/CFS)

Researchers have studied ME/CFS and the HPA axis since the 1980s. Here’s what they’ve found:

• People with ME/CFS often have low baseline cortisol levels, especially in the morning (1)

• They may also have a blunted response to stress, meaning their body doesn't make enough cortisol when needed  (1)

• The system’s “off switch” (called negative feedback) may be overly sensitive—so once cortisol is released, it shuts down too quickly (2)

• Childhood trauma, chronic infections (like Epstein-Barr Virus), and long-term stress can all contribute to HPA dysfunction (3)

  
  

In simple terms, the HPA axis in ME/CFS is like a fire alarm system that once went off too often—and now no longer responds properly to actual emergencies.

What About Long Covid?

Long Covid shares many symptoms with ME/CFS—and mounting evidence suggests the HPA axis may also be involved here.

• A 2022 review noted that cortisol levels in Long Covid patients are often low, and this may contribute to ongoing fatigue and stress intolerance (4)

• Autopsy reports have found microscopic damage to adrenal glands in people who died from COVID-19 (5)

• In a 2023 patient survey, many Long Covid sufferers had cortisol levels less than half of normal, with no compensatory rise in ACTH (the hormone that should stimulate cortisol production) (6)

• There's even some evidence that people who lost their sense of smell or taste (dysosmia/dysgeusia)—a common Long Covid symptom—may also have lower cortisol (7)

  
  

Researchers believe the virus may directly impact the endocrine system via ACE2 receptors, which are found in the adrenal glands, hypothalamus, and pituitary—the key players in the HPA axis.

Fibromyalgia: A Similar Pattern

In fibromyalgia, the evidence is mixed but points toward blunted or disrupted cortisol patterns, especially in response to stress (8).

• Studies have shown reduced 24-hour urinary cortisol levels, and a blunted response to stress tests like the Trier Social Stress Test (9) (10)

• However, some patients—especially those with depression—show slightly elevated levels. This shows how complex and individualized the HPA dysfunction can be (11)

• Many experts believe that chronic inflammation and central sensitization (an overactive nervous system) play a role—and the HPA axis struggles to regulate this (12)

  
  

Summary of What Research Shows

Condition	HPA Axis Changes
ME/CFS	Low morning cortisol, poor stress response, trauma link
Long Covid	Low cortisol in many cases, possible adrenal damage
Fibromyalgia	Blunted cortisol rhythm, poor recovery from stress

Supporting the HPA Axis: Nutrition and Lifestyle

Recovery from hypocortisolism requires a multi-faceted approach focused on restoring adrenal and gut function.

1. Remove Stressful Foods

Avoid:

• Alcohol and caffeine (disrupt sleep and stress response)

• Sugars, sweeteners, and refined carbs (promote inflammation and cortisol insensitivity)

• Processed foods and inflammatory oils (e.g., soybean, corn, sunflower oils)

  
  

2. Balance Blood Sugar

Blood sugar fluctuations can blunt the body’s cortisol response. Stabilize it by:

• Avoiding sugary spikes

• Eating protein with every meal

• Choosing complex carbohydrates and healthy fats

3. Emphasize Nutrient-Dense Foods

Focus on:

• High-quality proteins: poultry, fish, legumes, eggs, dairy, organ meats

• Healthy fats: olive oil, avocados, nuts, oily fish

• Colourful fruits & vegetables: rich in polyphenols and antioxidants

• Sea salt in moderation: supports adrenal function, especially if low blood pressure is present

  
  

4. Load Up on Antioxidants

Chronic oxidative stress disrupts cortisol synthesis. Prioritize:

• Vitamin C (bell peppers, kiwi, citrus, broccoli)

• Vitamin E (sunflower seeds, almonds, spinach)

• Carotenoids (carrots, sweet potatoes, leafy greens)

• Selenium (Brazil nuts, tuna, seeds – but don’t overdo Brazil nuts!)

• Zinc (oysters, red meat, pumpkin seeds)

• Vitamin B5 (avocados, eggs, mushrooms, liver)

• Magnesium and CoQ10 (nuts, leafy greens, beans, fatty fish)

  

5. Heal the Gut

• Eat 30g of fibre per day from diverse plant sources

• Include fermented foods: kefir, sauerkraut, kombucha, plain live yogurt

• Reduce sugar and additives that harm the microbiome

  
  

6. Support Mind-Body Balance

• Sleep: Crucial for cortisol rhythm; manage circadian rhythms and maintain consistent sleep schedules.

• Yoga: Reduces stress and anxiety by downregulating the HPA axis.

• Mindfulness meditation: Promotes emotional resilience and has moderate effects on stress and sleep.

• Breathwork: Practices like those in the Wim Hof Method have been shown to reduce perceived stress.

  
  

In Summary

Hypocortisolism is a real, measurable condition affecting a significant subset of people with ME/CFS, Long Covid and Fibromyalgia. Although not every patient will show clear hormonal deficiencies, the overall picture points to a dysregulated stress response system—one that is deeply intertwined with lifestyle, gut health, and psychological resilience.

Healing isn’t quick or linear, but by adopting a holistic, nutrition- and lifestyle-cantered approach, many people can find significant relief. The key is to nourish the body at every level—from hormones and nerves to microbes and mitochondria—and gently guide the system back into balance.