“Adrenal Fatigue”/HPA Axis Dysfunction: Key Supplements to Boost Your Energy and Stress Resilience

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HPA axis dysfunction known as “adrenal fatigue” is characterized by profound fatigue, difficulty handling stress, and a slew of other challenging symptoms. It is usually caused by an ongoing high-stress lifestyle. Although the biggest factor in getting better is figuring out how to manage the stresses of life, certain nutritional supplements may have a role.

Specific vitamins, minerals, and herbal extracts are known to influence neurotransmitter production and brain function. The brain controls the body’s biochemical pathways involved in stress management. For instance, adaptogens such as ashwagandha and rhodiola can help modulate the body’s stress response, potentially improving resilience to stress and helping in the regulation of cortisol levels. Magnesium, omega-3 fatty acids, and B vitamins are crucial for supporting neurological function and mood regulation, thereby indirectly supporting HPA axis health. By nourishing the body at a cellular level and supporting the systems involved in stress response, these supplements can help reduce the harmful effects of stress on the body and promote a more balanced state of mental and physical well-being.

What Is Adrenal Fatigue?

Adrenal fatigue is a term often used to describe a collection of symptoms that may occur when the body and mind are under chronic stress, leading to a dysfunction in the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is a central part of our stress response system, involving the interaction between the hypothalamus, pituitary gland, and adrenal glands. It regulates many body processes, including stress response, digestion, immune system, mood, and energy levels.

Healthcare providers recognize that what is termed “adrenal fatigue” is HPA axis dysfunction, which doesn’t imply that the adrenal glands are fatigued from overwork. Instead, it recognizes chronic stress leading to symptoms like fatigue through dysregulation of the body’s stress response system.

Common symptoms that suggest a person might be experiencing adrenal fatigue include persistent tiredness that isn’t relieved by sleep, difficulty getting up in the morning even after a full night’s sleep, reliance on caffeine or other stimulants to get through the day, and a feeling of being overwhelmed or unable to cope with stress. Other symptoms can include craving for salty or sweet snacks, a weakened immune response, and a slow recovery from illness or stress.

How Does The HPA Axis Work?

The Hypothalamic-Pituitary-Adrenal (HPA) axis is a complex network that orchestrates the body’s hormonal response to stress through a series of interactions and feedback mechanisms between the hypothalamus, pituitary gland, and adrenal glands.

  • Stress Causes Release of CRH from the Hypothalamus: The process begins when the hypothalamus perceives a stressor. In response, it secretes corticotropin-releasing hormone (CRH).
  • The Hypothalamus Makes ACTH: CRH then travels to the pituitary gland, stimulating it to release adrenocorticotropic hormone (ACTH) into the bloodstream.
  • The Adrenals Make Cortisol: ACTH acts on the adrenal glands, located on top of the kidneys, signaling them to produce and release cortisol, the body’s primary stress hormone.

Cortisol has several effects on the body, including mobilizing energy stores, suppressing the immune system, and helping to maintain blood pressure. It also has a negative feedback effect on both the hypothalamus and pituitary gland, regulating the stress response and ensuring the system does not become overactive.

This hormonal cascade allows the body to respond to stress in a coordinated and efficient manner, preparing it for a “fight or flight” response. Once the stressor is removed, cortisol levels decrease, inhibiting the release of CRH and ACTH, and the system returns to homeostasis. This feedback loop is essential for the body to respond appropriately to stress and recover afterwards.

Additionally, researchers are finding that there are changes in the actual sizes of parts of the brain affected by stress hormones. [PMC7364861]

Elevated cortisol levels, stemming from HPA axis dysfunction due to chronic stress, play a significant role in increasing gut permeability, also known as “leaky gut.” This condition arises when the intestinal wall becomes more permeable, allowing substances that are normally contained to leak into the bloodstream. Prolonged stress with elevated cortisol levels can weaken the intestinal barrier. The resulting increased gut permeability can trigger inflammation, an overactive immune response, and a range of health issues, from digestive disorders to systemic problems. Recognizing the link between HPA axis dysfunction, elevated cortisol, and gut health is key to understanding the health implications of chronic stress.

How Does Cortisol Affect Sleep and Wakefulness?

Cortisol is often referred to as the “stress hormone,” but it is also intricately tied to the body’s circadian rhythm, so it fluctuates in a normal pattern throughout the day. If the Hypothalamic-Pituitary-Adrenal (HPA) axis becomes dysregulated by chronic stress, the result can be abnormal levels of cortisol. Here’s how it works.

Normal Fluctuation of Cortisol Levels:

  • Morning: Cortisol levels peak in the early morning, usually around 30 minutes after waking, in a surge known as the cortisol awakening response (CAR). This peak helps promote wakefulness and provides energy for the day ahead.
  • Daytime: After reaching its peak, cortisol levels gradually decline throughout the day, decreasing energy levels and preparing the body for rest.
  • Night: Cortisol levels reach their lowest point at night, facilitating sleep and allowing the body to recover and repair.

Altered Cortisol Levels and Their Effects:

  • Sleep: Elevated nighttime cortisol levels can disrupt the body’s natural sleep-wake cycle, making it difficult to fall asleep or stay asleep. Low levels in the morning can make waking up more challenging, leading to a feeling of grogginess or unrefreshed sleep.
  • Wakefulness: Abnormally high cortisol levels during the day can lead to heightened alertness and anxiety, making it hard to relax. Conversely, lower-than-normal daytime levels can result in fatigue and decreased energy, affecting overall alertness and mood.
  • Fatigue: Chronic stress and consequent dysregulation of cortisol can lead to sustained high levels of cortisol or a flattened day-night curve, where the natural peak and trough pattern is lost. This can result in persistent fatigue, as the body misses out on the natural rhythm that helps regulate energy levels.

In essence, the HPA axis and cortisol levels play a critical role in regulating the body’s daily cycle of sleep, wakefulness, and energy use. Disruptions in this cycle can significantly impact physical and mental health, leading to sleep disorders, chronic fatigue, and other stress-related conditions.

What Food and Lifestyle Factors Are Important For Managing Adrenal Fatigue?

Managing adrenal fatigue, or more accurately HPA axis dysfunction, involves a comprehensive approach that includes both dietary and lifestyle modifications. Here’s a guide to the essential food and lifestyle factors that can support adrenal health and help manage stress:

Food Factors:

  • Balanced Nutrition: Emphasize a diet rich in whole foods, including fruits, vegetables, whole grains, lean proteins, and healthy fats. Such a diet ensures a steady supply of essential nutrients that support adrenal function, like vitamin C, B vitamins, magnesium, and omega-3 fatty acids.
  • Regular Meals: Eating regular, balanced meals and snacks helps maintain stable blood sugar levels, reducing stress on the adrenals.
  • Hydration: Inadequate water intake can contribute to feelings of fatigue. Getting enough water intake is crucial for overall health and can help the body manage stress more effectively.
  • Limit Stimulants: Reduce intake of caffeine and sugar, which can exacerbate adrenal fatigue by causing spikes and crashes in blood sugar and cortisol levels.
  • Increase Intake of Adrenal-Supportive Foods: Foods rich in vitamins and minerals that support adrenal health include leafy greens, nuts, seeds, fish, and seaweed.

Lifestyle Factors:

  • Stress Management: Techniques such as meditation, yoga, deep breathing exercises, and mindfulness can reduce perceived stress and its impact on the HPA axis.
  • Adequate Sleep: Ensuring 7-9 hours of quality sleep per night can significantly impact adrenal health and stress resilience.
  • Moderate Exercise: While vigorous exercise might be too stressful for those with adrenal fatigue, gentle activities like walking, yoga, and swimming can be beneficial.
  • Reduce Overcommitment: Learning to say no and reducing the number of commitments can help lower stress levels.
  • Social Support: Maintaining a supportive network of friends and family can provide emotional support and reduce stress.
  • Limit Exposure to Toxins: Reducing exposure to environmental toxins and choosing clean, organic foods when possible can help minimize additional stress on the body.
  • Mindful Practices: Engaging in activities that promote relaxation and joy, such as hobbies, reading, or spending time in nature, can improve mental health and stress management.

By incorporating these food and lifestyle changes, people can support their body’s ability to manage stress, potentially reducing the fatigue associated with HPA axis dysfunction. It’s important to approach these changes gradually and consider working with a healthcare professional to tailor a plan that suits your individual needs and circumstances.


Dietary supplements are not designed to diagnose, treat, cure, or prevent any disease. This article aims to offer valuable insights into which nutritional supplements have undergone scientific study and shown promise in supporting specific health conditions. We break down the research, so you can work with your medical providers to make informed decisions about adding supplements to your health regimen. For personalized advice tailored to your needs, we recommend consulting with a registered dietitian in addition to your primary care provider.

Check with your physician when adding supplements. While supplements are generally safe for most people, do not add nutritional supplements without your physician’s specific approval if you are pregnant or nursing, are undergoing cancer treatment, have a history of organ transplant, liver or kidney disease, or take medications that interact with supplements.


For managing symptoms associated with HPA axis dysfunction, often referred to as “adrenal fatigue,” certain nutritional supplements are recommended to support adrenal health and stress response:

  • Adaptogens: Herbs like ashwagandha, rhodiola rosea, and holy basil help balance cortisol levels and improve the body’s resilience to stress.
    • Ashwagandha: This adaptogen has significant impact on reducing cortisol levels and supporting adrenal health.
    • Ginseng: Asian (Panax) ginseng is another adaptogen that can help improve stress resilience, enhance mental performance, and support energy levels.
    • Rhodiola Rosea: Also highlighted for its adaptogenic properties, Rhodiola is particularly noted for its ability to help combat fatigue and improve stress tolerance.
    • Holy Basil (Tulsi): An adaptogenic herb that helps counteract stress effects, balances cortisol levels, and promotes mental balance.
  • Magnesium: Known as a calming mineral, magnesium supports nervous system health and can help improve sleep quality and reduce fatigue.
  • Multivitamins: A good quality multivitamin can supplement the following:
    • Vitamin C: Essential for adrenal gland function, vitamin C helps regulate cortisol and supports the immune system.
    • B Vitamins: Particularly B5 (pantothenic acid), B6, and B12, these vitamins are crucial for energy production and supporting the body’s stress response. [PMC6770181]
    • Zinc: Important for neurotransmitter function and overall immune health, zinc can support the body’s ability to handle stress.
    • Vitamin D: Often referred to as the “sunshine vitamin,” vitamin D deficiency has been linked to mood disorders and fatigue. Supplementing with vitamin D may support overall mood and energy levels.
    • Selenium: An antioxidant that is essential for thyroid and adrenal gland health. Selenium can help regulate the production of reactive oxygen species within these glands.
  • Omega-3 Fatty Acids: Found in fish oil supplements, omega-3s can help reduce inflammation and support brain health, impacting mood and stress management.
  • Probiotics: Gut health is linked to mood and stress levels; probiotics can support a healthy gut flora, which may positively affect the HPA axis.
  • L-Theanine: An amino acid found in green tea, L-Theanine promotes relaxation without drowsiness, helping to manage stress and anxiety. It also helps reduce “jitters” related to caffeine intake.
  • More:
    • Phosphatidylserine: This phospholipid plays a crucial role in cell membrane integrity and may help decrease the effects of stress on the body by reducing cortisol levels. In a placebo-controlled study, 9 men took 800 mg/d phosphatidylserine for 10 days. This significantly blunted the ACTH and cortisol responses to physical exercise. The researchers concluded that phosphatidylserine may counteract stress-induced activation of the hypothalamic-pituitary-adrenal axis. [PMID: 1325348]
    • Cordyceps: A type of medicinal mushroom that may improve energy, endurance, and stress resistance by supporting mitochondrial function and oxygen utilization.
    • Ginkgo Biloba: Known for its benefits on cognitive function and circulation, Ginkgo Biloba can also aid in stress management by improving stress adaptation and reducing symptoms of anxiety.
    • Inositol: Sometimes used to manage anxiety and depression, inositol can help modulate the action of neurotransmitters and support a balanced mood.
    • Curcumin: The active component of turmeric, curcumin has potent anti-inflammatory and antioxidant properties that can help mitigate the physical effects of stress on the body.
    • Licorice Root: In moderate amounts, licorice root can help prolong the life of cortisol in the body, though it should be used cautiously and not recommended for those with high blood pressure.

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Supplement Safety Information

The safety profile of adaptogens, magnesium, multivitamins, fish oil, probiotics, and L-theanine is favorable, overall. When consumed within recommended guidelines, these supplements are well-tolerated by most people. Adaptogens have a long history of use, with minimal adverse effects reported. Magnesium is essential for numerous physiological functions. Multivitamins provide a broad spectrum of nutrients to support overall health, with a very low risk of side effects when taken as directed. Fish oil is widely recognized for its heart health benefits and is considered safe for daily intake, with quality products minimizing any concerns related to contaminants. Probiotics are generally regarded as safe, contributing to gut health and balance without significant side effects. L-theanine is known for its calming effects and is also safe for most people when used in moderation. It’s always prudent to consult with a healthcare professional before incorporating any new supplements into your routine, particularly to address specific health conditions or to avoid potential interactions with medications.

Medication Interactions

  • Anticoagulants and Antiplatelets: These medications, including warfarin and aspirin, may have increased bleeding risks when taken with fish oil due to its blood-thinning properties.
  • Antihypertensives: Blood pressure medications could interact with fish oil, potentially enhancing their blood pressure-lowering effect. Magnesium and adaptogens like rhodiola may also lower blood pressure, necessitating monitoring for low blood pressure.
  • Antibiotics: Certain antibiotics can be affected by magnesium and multivitamins because minerals like magnesium can bind to the antibiotics, reducing their absorption and effectiveness. It’s recommended to separate the intake of these supplements and antibiotics by a couple of hours.
  • Diabetes Medications: Magnesium and adaptogens may affect blood sugar levels, potentially requiring adjustments in diabetes medication dosages to prevent low blood sugar.
  • Central Nervous System Depressants: L-theanine may increase the sedative effects of medications that cause sedation or drowsiness, including benzodiazepines and some antidepressants, leading to increased sedation.
  • Immunosuppressants: Since adaptogens and probiotics can modulate immune system activity, they may interact with immunosuppressive drugs by possibly altering their intended effects.
  • Thyroid Hormones: It’s advisable to take supplements and thyroid hormones at different times of the day.

Supplement Interactions

  • Adaptogens: May enhance the effects of other stress-relieving supplements like L-theanine, potentially leading to over-relaxation or sedation, and combining with stimulant-based supplements (like caffeine or guarana) might reduce their intended energizing effects.
  • Magnesium: Can interact with calcium supplements, as excessive amounts of one can inhibit the absorption of the other, affecting bone health. Taking zinc supplements alongside magnesium without balancing their intake can lead to imbalances, as high doses of zinc can hinder magnesium absorption.
  • Multivitamins: May lead to excessive intake of certain nutrients when taken with single-nutrient supplements (like vitamin D or iron), increasing the risk of toxicity. Fat-soluble vitamins (A, D, E, K) within multivitamins can interact with omega-3 fatty acids in fish oil, potentially enhancing absorption but also increasing the risk of vitamin toxicity if not monitored.
  • Fish Oil: When taken with vitamin E supplements, may increase the antioxidant effect but also the risk of bleeding, as both can have anticoagulant properties. Combining with garlic supplements could further enhance fish oil’s blood-thinning effect, increasing bleeding risk.
  • Probiotics: Combining with antibiotic supplements (like allicin from garlic or berberine) might reduce the effectiveness of probiotics, as these supplements can have antibacterial properties that affect gut flora. Taking fiber supplements might enhance the growth and activity of probiotics, improving their efficacy in supporting gut health.
  • L-Theanine: Combining with caffeine supplements can modulate caffeine’s stimulating effects, promoting a more focused and less jittery energy. When taken with other calming supplements (like valerian root or melatonin), L-theanine might enhance their sedative effects, potentially leading to excessive drowsiness.

Food First!

Although this article discusses supplements in detail, don’t forget that we are absolutely committed to the “Food First” approach to nutrition. When it comes to your health, the totality of your eating habits far surpasses the impact of individual nutrients or any single supplement you consume. Even though this article doesn’t delve into the broader picture of your overall diet, it’s crucial to keep this element at the forefront of our minds. Your food needs to provide all the vitamins, minerals, fiber, and phytochemicals to nourish your body systems down to the cellular level.

Food choices, rather than supplements, are the most critical factors for a healthy gut microbiome. These trillions of tiny inhabitants in your gut affect your brain waves; they orchestrate your immune system. They possess the power to create molecules that can switch genes on or off and are even capable of synthesizing neurotransmitters. Opting for organic foods and steering clear of plastic packaging (including those labeled BPA-free) is a smart move to limit toxin exposure. The sum of all these parts leads to a powerful conclusion: the ultimate key to your health lies in the quality and balance of the food you consume. Supplements are secondary.

What To Eat

What Lab Tests Might Help Diagnose and Manage Adrenal Fatigue?

Testing For Cortisol Levels

A Salivary Cortisol Test (affiliate link) can help you and your physician decide if this type of stress hormone disruption is involved in your fatigue symptoms. This lab can be ordered in the NutriScape Lab Shop.

To Sum It Up

The strategic use of supplements including adaptogens, magnesium, multivitamins, fish oil, probiotics, and L-theanine offers a complementary approach to managing the symptoms associated with “adrenal fatigue”, or HPA axis dysfunction. Each of these supplements brings unique benefits to the table: adaptogens for stress resilience, magnesium for relaxation and sleep, multivitamins for overall nutritional support, fish oil for inflammation reduction and cognitive health, probiotics for gut-brain axis balance, and L-theanine for focused relaxation. Together, they can form a holistic strategy to support adrenal health and improve the quality of life for those struggling with chronic stress and fatigue.

While these supplements provide valuable support, it’s crucial to remember that they are part of a broader approach to wellness that includes diet, lifestyle changes, and professional guidance. A Dietitian can offer tailored recommendations based on your individual health status, dietary needs, and lifestyle factors, helping you navigate the journey toward optimal health with confidence.


This Article is Not a Substitute for Medical Advice

Dietary supplements are not designed to diagnose, treat, cure, or prevent any disease. The Supplement Sciences website seeks to provide comprehensive access to the most relevant supplement information along with convenient online ordering. We do not provide medical advice and cannot guarantee that every product suggested is completely without risk. Since each person is unique in their health history and medication use, it is important to discuss supplements with your personal physician. Specifically, pregnant women and individuals being treated for cancer or liver or kidney problems must consult their physician about every nutritional supplement they plan to take. People taking medications for the treatment of HIV or with a history of organ transplant must not take supplements without consulting with their physician.


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