Adaptogens, Stress, and the HPA Axis

By Dr. Linda J. Dobberstein, DC, Board Certified in Clinical Nutrition

June 3, 2019

Adaptogens, Stress, and the HPA Axis
Too much or too little. Overstimulated or exhausted. These are examples of loss of stress tolerance that can affect all bodily systems. Your body is in a state of constant adaptation to daily needs and stressors in order to keep balance, or homeostasis. Homeostasis is fundamental to healthy function and aging well. Yet, millions of individuals struggle with maintaining health while under numerous stressors. Over 75 percent of patient visits to primary care physicians are due to stress. Nutritional support with adaptogenic herbs like cordyceps, holy basil, eleuthero, and rhodiola provide impressive support for stress tolerance and may help you restore your vitality.

Stress and HPA Axis

Stress comes in numerous forms including infections, toxins or other immune challenges, blood sugar, circadian rhythm disruptions, nutrient poor diet, sleep problems, and actual or perceived stress from physical or mental situations. Add a fast-paced life and constantly pushing the limits and you will eventually experience ongoing fatigue, feeling old and worn out, and a general loss of vitality.

This reflects a loss of homeostasis to the stress management system of your body. Some individuals might think this is “normal aging”, but what if this happens when you are in your 40’s or 50’s or younger? Understanding a few key elements can help you make better choices for your health.

At the heart of physiological homeostasis is the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus gland, which is part of the limbic system in the brain, is the central command center and conductor of a highly sophisticated neuroendocrine relay system. The hypothalamus governs basic functions like hunger, sleep, mood, sex drive, temperature regulation and thirst. It affects metabolism and body weight, electrolytes, and fluid balance.

The hypothalamus as a commander sends signals to the pituitary and subsequently to the adrenal glands. The pituitary is like a co-pilot and the adrenal glands are the work crew. They are in constant communications with the use of adrenal steroid hormones cortisol, DHEA, etc. and neurotransmitters like serotonin, dopamine, norepinephrine, epinephrine, acetylcholine, GABA and glutamate working with the autonomic nervous system. The HPA axis also affects the thyroid, sex hormones, growth hormone, and other hormone signals and pathways.

Three Stages of HPA Axis Imbalance

The HPA axis and the autonomic nervous system (ANS) silently monitor your body at all times. If they sense trouble or need to respond to any kind real or perceived stress, then your neuroendocrine system goes into an active “fight-flight” sympathetic autonomic nervous system stress mode. If the stress is resolved and your HPA axis system is healthy, all of the stress hormones and neurotransmitters down-regulate and everything goes back to being “cool” with the “rest-relax” parasympathetic autonomic nervous system.

On the other hand, if the stressors continue without resolution, then your neuroendocrine system gets dysregulated and “hot” and the sympathetic ANS stays engaged. As the system remains “on” and “hot” from too many demands than further long-standing dysregulation occurs. There are three main stages of HPA axis dysfunction. 1) Stressed and Wired. 2) Stressed and Tired 3) Exhaustion.

1) Stressed and Wired is the first stage of HPA axis distress. It reflects that the body is running in a state of alarm. The sympathetic autonomic nervous system, brain, and adrenal glands are in hyperdrive. High amounts of stress hormones and neurotransmitters are released in order to meet ongoing unrelenting demands.

You may feel wired, ramped-up, anxious and restless and have trouble getting to sleep and staying asleep. You may be more apt to catch the latest cold or germ. Caffeine and other stimulants accentuate this response. Getting out the door in the morning, with kids to school and yourself to work, while fighting traffic is a daily activity that ramps up the HPA axis for many individuals.

2) Stressed and Tired is the second stage of HPA axis dysregulation. Hormone and neurotransmitter levels may appear “normal”, but the “gas tank gauge” is fluttering towards empty with occasional rebounds of energy.

With this scenario, you may be able to meet the demands of the day, but as soon as you sit down, you crash or fall asleep. Your sleep rhythm may be off and blood sugar levels often fluctuate with hypoglycemia and insulin resistance. Your ability to repair from the day’s activity is compromised which makes it hard to get out of bed in the morning and feel refreshed. This is the “walking wounded”.

3) Exhaustion is the third stage of HPA axis dysregulation. At this point, your nervous system and adrenal glands can no longer muster up a response to adequately deal with life stressors. Severe, often incapacitating fatigue, imbalanced blood sugar and blood pressure concerns arise, significant mood stress occurs, along with hormone imbalances, oxidative stress, autoimmune disorders and conditions with “-itis”occur. The “walking wounded” are on thin ice and you may feel broken and ready to crumble with the slightest stressor.

The overall goal is to prevent the slide into any of these stages before they happen. If you find yourself in one of these categories, then it is time to work on rebuilding and repair. Life events and demands often outweigh the ability to rest and repair.

Whether you are high achiever looking to conquer the world, a high school or college student with academic demands, extracurricular activities and a job, an adult raising kids, working multiple jobs, and taking of parents, or you have reached the point of retirement and your “get up and go” has gone, you must support your body and regain stress tolerance. Adaptogenic herbs can help feed and support your HPA axis neuroendocrine system and assist in maintaining balance.


Adaptogenic herbs such as cordyceps, holy basil, eleutherococcus, and rhodiola rosea have been used for thousands of years. These herbs are hailed to be some of the most powerful adaptogenic tools for improving stress tolerance and bringing vitality to the body by supporting the HPA axis and homeostasis.


Cordyceps is a prized medicinal mushroom that has been used as a tonic and health supplement traditionally in Asia. It is often used to help with exhaustion and loss of function including in seniors. This centuries-old prized Chinese herbal tonic contains several active components that demonstrate powerful activity throughout multiple systems of the body.

The journal Evidenced Based Complementary Alternative Medicine’s nicely summed up the actions of the herb cordyceps in review study. Cordyceps is widely used to aid as an antioxidant, for immune modulatory and general immune support, liver, heart, lungs, sexual vitality, adrenal gland and kidney support, cholesterol and blood sugar metabolic support, anti-aging, cell clean-up, oxidative stress, and supports protection of the brain from stressors. Cordyceps sinesis is often referred to as “Himalayan Gold”.

Cordyceps reduces stress and fatigue changes associated with the adrenal glands, spleen, thymus, and immune concerns. It is also a valued adaptogen for thyroid health. Research published December 2018 shows that cordyceps helps aid the brain in time of oxidative stress and significant wear and tear by healthfully supporting glial cells, myelin, and cytokines.

Cordyceps affects production of energy or ATP. Cordyceps helps manage sleep cycle regulation and increases NREM sleep as it supports theta waves in the brain. Cordyceps active ingredients help promote deeper restorative sleep and buffers against stimulatory stress. It assists the heart, mood and mitochondria in protection from stress. Cordyceps may also aid in helping restore energy and immune vitality after the stress of illness and athletic training and events

Holy Basil

Holy basil, considered an incomparable, elixir of life of traditional Indian medicine has been used and even worshipped in Ayurvedic medicine for over 3,000 years due to its healing properties. Holy basil provides adaptogenic activity as an antioxidant, natural analgesic, and helps manage and support stress hormones and neurotransmitters with the HPA axis.

It supports the brain with mental, cognitive, and mood stress. It aids protection against industrial pollutants and heavy metals chemical stress and physical stress from overdoing it or prolonged physical activity and cold environmental temperatures. Holy basil supports healthy cholesterol and blood sugar management under stress. Holy basil is considered an “Ayurvedic herb for all reasons”.

A double-blind, placebo-controlled study evaluated the effect of OciBest®, a standardized extract of holy basil on stress. Prior to the study, participants experienced ongoing stress symptoms of headache, heart palpitations at rest, trouble with hearing, blurred vision, forgetfulness, sexual problems, frequent GI symptoms, lack of appetite, muscle tics and tremors, irritability, exhaustion or feeling overworked, sleep problems, and avoided people or tasks.

One group was supplemented with OciBest® holy basil for 6 weeks versus those who received no support. Individuals who received the holy basil experienced a marked reduction in stress-related symptoms. Forgetfulness, sexual problems of recent onset, exhaustion, and frequent sleep problems improved the most.

Holy basil research shows that it can help your nervous system dealing with the stress of noise. Considering how many people work or live in busy, noisy environments, holy basil offers a highly promising agent to help counteract the exhaustion caused by noise stimulus.

Eleuthero Extract

Eleutherococcus, also known as Siberian ginseng or eleuthero, offers profound adaptogenic support for many different stress-related concerns. A 2015 Journal of Internal Medicine Research study found significant improvements in burnout when eleutherococcus extract was used for 12 weeks.

The double-blind, placebo-controlled study of professional adults received a placebo or eleutherococcus extract. Those taking the adaptogenic herb had marked improvement in all concerns associated with burnout as compared to those who received placebo.

Sleep deprivation is a major concern for many individuals. It greatly impacts HPA axis function and stress tolerance. Use of eleutherococcus in sleep deprived individuals led to improvement in cognitive skills, memory, and behavior.

Eleutherococcus and another adaptogenic herb - rhodiola rosea are often combined together as both support the HPA axis. Eleutherococcus increased endurance, strength and mental performance and rhodiola improved attention, cognitive function and mental performance in fatigued individuals. A review study confirmed that rhodiola and eleutherococcus provide strong effects for stress protection in mental and behavioral health.

Rhodiola Rosea

Rhodiola rosea has been part of traditional medicine systems in parts of Europe, Asia, and Russia for centuries for immune support, fertility, strength, endurance, and vitality. Today, rhodiola rosea is often used to help recover from professional burnout, mental fatigue, and support physical well-being. Researchers evaluated rhodiola’s impact with physician burnout and college students during exams.

Results showed significant improvement in physician burnout and fatigue levels with two weeks of supplementation. No adverse effects were noted. Dosages include 200-680 mg of rhodiola per day for physical fatigue and 100-576 mg per day for mental fatigue.

Students going through exams were placed on either placebo or rhodiola at 100 mg per day for 20 days. Improvements were noted in hand-eye coordination, mental energy, and general well-being with improvement noted in HPA stress tolerance compared the students that received the placebo. No adverse effects or toxicity concerns were experienced.

Athletes who received rhodiola for four weeks experienced improved exercise and endurance capacity as well as an improvement in cardiac-respiratory measurements. Other research demonstrates rhodiola’s benefit for mood stress and was better tolerated than common medications used for mood support.

Stress, Genes and Rhodiola

Stressful events trigger many changes in the brain and HPA axis neuroendocrine system. On a deeper level, genetic expression is also affected by stress. This is partly due to stress effects on methylation. Methylation requires several nutrients like many B vitamins, choline, glutathione, and magnesium. These nutrients are rapidly used during high demands by the neuroendocrine system. In the case of rhodiola rosea, it too aids in protection of genetic expression challenged by stress and may be used with these other nutrients for greater support.

A 2014 study had some rather impressive findings on rhodiola’s impact on genetic signaling. Rhodiola was found to target over 1,000 genes that regulated cellular responses, affecting multiple signaling pathways and molecular networks. Benefits were found particularly with emotional and agitated behavior, glutamate excess and negative moods. Rhodiola assisted with several genes that affected neurological cardiovascular, metabolic, endocrine, and gastrointestinal health.

Gamma Oryzanol

Gamma oryzanol is a bioactive phytochemical extracted from brown rice bran and rice bran oil. It is not a strict adaptogenic herb like the others discussed in this article. It does however support many aspects of healthy stress adaptation and metabolism.

Gamma oryzanol provides support as an antioxidant, cellular stress and wear and tear management, cholesterol and blood sugar support, GI protection, histamine buffering, and cellular protection. It helps regulate leptin and adiponectin levels which affects appetite, weight management, and fat burning. Even in the context of a high fat, high sugar diet, gamma oryzanol can help manage blood sugar distress that impacts the HPA axis.

Adaptogenic herbs have stood the test of time as they have been used literally over thousands of years to help mankind deal with innumerable life stressors and restoration of vitality. Current research explores the reasons behind the reliance of these herbs and the results are impressive.

Adaptogenic herbs have the propensity to positively support the HPA axis and regulate all types of cellular responses and organ systems related to stress and homeostasis. If you find yourself stressed and wired, wired and tired or simply exhausted and distressed consider using cordyceps sinesis, holy basil, eleutherococcus, and rhodiola rosea to help restore vitality.

Adaptogenic herbs may be used with other nutrients like B vitamins, vitamin C, magnesium, coenzyme Q10, astaxanthin, acetyl-l-carnitine, fisetin, curcumin and many others for stress tolerance restoration. Combine this with nutrient-dense meals, restorative sleep support, appropriate physical activity, play time, and active intentional rest. It may just put that spring back in your step!

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