Doctors specializing in environmental or integrative medicine have found that many of their patients have poor adrenal function (also known as adrenal fatigue or hypoadrenia) and that after taking steps to correct this their condition has improved, sometimes quite dramatically. While still a controversial diagnosis within conventional medicine (Mayo Clinic) due to lack of research, addressing adrenal fatigue is regarded as vital by organizations such as The Institute for Functional Medicine (IFM).
The Adrenal Glands
The adrenal glands are located above the kidneys and produce a large number of hormones. The cortex (outer part) produces corticosteroids made from cholesterol, these include cortisol, dehydroepiandrosterone (DHEA), aldosterone and the sex hormones, testosterone and estrogen. Cortisol is the major hormone involved in the stress response. In the medium term it is helpful as it is needed to regulate blood sugar metabolism and to prepare the body in case of injury, among other actions, to make sure the body is prepared for action. Under prolonged stress however cortisol levels remain elevated, causing high blood pressure and blood sugar imbalances and suppressing the inflammatory response of the immune system. DHEA is thought to counteract the negative effects of prolonged high cortisol levels such as immune suppression and damage to brain cells through over stimulation. DHEA levels decline with age which has caused some people to label it as the master anti-aging hormone. This may or may not be the case but in studies it has certainly been shown to increase energy and feelings of well being. The adrenal medulla (central part) makes adrenaline and noradrenaline, the substances that produce the "fight-or-flight response" when stimulated by the autonomic nervous system, giving that unmistakable short-term burst of energy that enables you to overcome whatever danger is present.
What is Adrenal Fatigue?
Adrenal fatigue occurs when the adrenal glands are no longer able to adequately control the stress response with the result that cotrisol, DHEA, and other hormones are produced in abnormal amounts (either high or low) and the patient experiences symptoms including fatigue and mood disturbances. Adrenal fatigue is usually caused by chronic stress, whether that stress is mental, emotional, physical, or environmental (e.g. infection, exposure to toxins, nutritional deficiency).
Adrenal fatigue is frequently described as occuring in four distinct stages usually defined in terms of hormone output. These four stages are as follows:
Stage 1: Alarm Reaction - This is what we commonly call the "fight-or-flight" response and is a healthy reaction in which the body reacts aggresively to a stressor, or stressors, and mounts a strong anti-stress response to overcome them. The adrenal glands increase their output of stress-mediating hormones including cortisol and DHEA but this level of output is well within the glands normal capacity. At this stage no symptoms are present and physiological dysfunction is undetectable.
Stage 2: Resistance Response - With chronic or severe stress the capacity of the adrenal glands to cope is eventually exceeded and they begin to struggle to meet demands for cortisol and DHEA production. At this stage cortisol levels are constantly elevated but DHEA may start to decline. The imbalance between the levels of these two hormones is thought to underly the symptoms that begin to emerge at this stage. The individual will still be able to carry out their normal daily routine but is likely to experience increasing levels of fatigue at the end of the day and require more rest and sleep to recover. Sleep may be unrefreshing so the person still feels tired in the morning. Other symptoms may also appear including anxiety, irritability, and insomnia. Thyroid function may also start to decline and bring with it yet more symptoms at this stage due to the close connection between adrenal and thyroid function (see below).
Stage 3: Adrenal Exhaustion - If the sources of stress are not reduced and continue unabated, adrenal function will decline further. At this stage the adrenal glands are unable to keep up with the body's constant demands for cortisol production, and this too now begins to decline; both DHEA and cortisol may now be low on diagnostic tests. The decline in cortisol production is usually gradual but steps must be taken to avoid progression to stage 4. At stage 3 the body slows down, or begins to shut down, many of its non-essential functions (e.g. reproduction) with the main focus on the conversion of energy for survival. The patient will experience increasingly severe aches and pains, muscle weakness, loss of exercise tolerance, brain fog, insomnia, and depression. Toxins will also build up as detoxification processes slow. The sufferer will almost certainly be struggling badly with daily living and may even be unable to take care of themselves.
Stage 4: Adrenal Failure - Eventually, the adrenals become completely exhausted and unable to function. At this stage the patients' condition is akin to adrenal insufficiency, or Addison's disease. Output of adrenal hormones is so low that there is a high risk that even essential metabolic processes cannot be maintained. The patient in stage 4 is at risk of experiencing the symptoms of an Addisonian crisis which include sudden penetrating pain in the lower back, abdomen, or legs, severe vomiting and diarrhoea, dehydration, low blood pressure, and loss of consciousness. If treatment of such a crisis is not swift there is the risk of heart failure, and death. It must be pointed out that it will usually take many, many years to reach this stage and almost all patients will seek help before it ever becomes a possibility, but in theory the risk is there.
The Adrenal Glands in Environmental Illnesses
According to Dr. Jacob Teitelbaum who has worked extensively with CFS and fibromyalgia patients and had papers detailing his effective treatment regimen published, up to two thirds of sufferers have adrenal fatigue. There are a number of reasons why this may be the case. It has been found that CFS and fibromyalgia patients have low corticotropin-releasing hormone (CRH)1. This is a hormone produced by the hypothalamus in the brain that signals the release of another hormone, ACTH, that tells the adrenal glands to increase their hormone output. If CRH is low then adrenal hormones will also be low. Many CFS patients also show a response to ACTH that is similar to that found in secondary adrenal insufficiency disease.
Another reason for low adrenal function could be what is known as adrenal fatigue or adrenal exhaustion. When humans were hunter-gatherers there were large periods of time between exposures to stressful situations in which the body could recover. Nowadays the fight-or-flight response is activated many times a day for most people so the body never gets chance to recover and levels of stress hormones may be chronically raised. Over time the adrenal glands may be unable to keep up this pace of hormone production due to exhaustion of nutritional reserves or damage to the gland itself and the result is low production of adrenal hormones and resulting symptoms of illness such as fatigue. This condition is what is referred to as adrenal fatigue or adrenal exhaustion. Dr. Teitelbaum notes that one of the first doctors to research stress reactions, Dr. Hans Seyle, found that the adrenal glands of severely stressed animals first begin to bleed and show signs of destruction before the animal finally dies. It may be that the modern human lifestyle for many people produces a less severe form of this. Whatever the cause, be it low CRH causing understimulation of the adrenal glands or adrenal exhaustion, it has been shown in multiple studies that people suffering from CFS, fibromyalgia and other environmental illnesses have low output of the adrenal hormones cortisol and DHEA2, 3, 4.
The Effects of Low Adrenal Function
The are a number of symptoms associated with low adrenal function and they will be familiar to any sufferer of environmental illnesses. The most common and troublesome include:
- Poor response to stress
- Exercise Intolerance
- Depression, Anxiety, and Insomnia
- Cognitive Dysfunction (Braing Fog, Poor Memory & Concentration etc)
- Hypoglycemia (low blood sugar)
- Low blood pressure and dizziness upon standing up
- Recurrent and persistent infections
Some of the main jobs of the adrenal glands are to regulate arousal and control blood sugar levels so these symptoms are what you would expect when they are functionally below normal levels.
Testing Adrenal Function
Many of the testing laboratories mentioned throughout this site offer diagnostic tests for adrenal function. These usually involve taking saliva samples at set times throughout the day at home and sending them back to the lab for analysis. Several samples are needed at different times as adrenal hormone levels naturally rise and fall during the day. These tests indicate levels of cortisol and DHEA/DHEA-S (the sulfur salt of DHEA) and a result indicating low levels would indicate that therapy aimed at increasing adrenal activity may be beneficial. These tests are easy to complete and relatively inexpensive.
More on the Adrenal Stress Index (ASI) test
Treating Low Adrenal Function
If you are found to have low adrenal function there are a number of options available for treating the problem. Many of these treatments will also help with many other problems associated with environmental illnesses as well.
Treating Hypoglycemia - As mentioned earlier the adrenals are involved in maintaining blood sugar levels and low adrenal function leads to low blood sugar. Treating hypoglycemia will relieve, to some extent, symptoms such as fatigue, brain fog, headaches, lightheadedness/dizziness, muscles aches, spaced out feelings. It will also take stress off the adrenal glands and allow them recover somewhat, which in turn will also help maintain blood sugar balance.
Treating hypoglycemia involves adhering to a diet low in fast releasing sugars. These are sometimes difficult to spot on food labels but the general rule is that the names end in 'ose', e.g. sucrose, fructose, dextrose. Basic rules of the hypoglycemic diet are:
- Decrease fast releasing sugar consumption
- Decrease consumption of stimulants such as caffeine
- Increase intake of complex carbohydrates like grains.
A useful supplement for hypoglycemia is glucose tolerance factor (GTF) chromium. A dose of 200-300 micrograms (mcg) twice a day is usual.
Nutrients and Herbs - There are a number of nutrients and herbs that may benefit adrenal function. The most widely used are:
Vitamin B5 (Pantothenic Acid) - A large proportion of vitamin B5 absorbed from the GI tract is stored in the adrenal glands14. It is a major component of coenzyme A (CoA) which is an enzyme at the heart of numerous biochemical reactions including energy production and the synthesis of neurotransmitters. Important here is the fact that pantothenic acid and its product CoA are required for the production of steroid hormones by the adrenal glands14 which is why a sufficient supply is essential in states of adrenal fatigue. Pantothenic acid is widespread in the diet and good sources include whole grains, broccoli, avocados, mushrooms, and organ meats. Supplements are cheap and widely available. The more bioactive pantethine, which is a step closer to CoA, is also available as a supplement but is more expensive.
Vitamin C (Ascorbic Acid) - The adrenal glands contain more vitamin C than any other organ in the body, suggesting an important role in the stress response14. Indeed, during stress the adrenal glands secrete vitamin C along with the stress hormones, although only locally; it is thought that this vitamin may therefore regulate the functioning of the adrenal glands15. As a result, the body's requirements for vitamin C increase in times of stress and when chronic stress is present14. Vitamin C is found in a wide variety of fruits and vegetables and supplements are inexpensive. Buffered supplement forms such as calcium and magnesium ascorbate help to avoid digestive upsets due to vitamin C's acidity.
Licorice - Contains a compound called glycyrrhizin which raises the body's level of cortisol by inhibiting its breakdown5. As such licorice acts as an adrenal stimulant. A common dosage is 2-3 grams of licorice root (make sure it's not de-glycyrrhizinated licorice or DGL) twice a day. It is best to use licorice only for a maximum of 8 weeks before tapering off the dosage as it can raise cortisol levels too high and cause high blood pressure as well as interfer with fluid balance if taken chronically due to its effect on mineralcorticoid hormones.
Asian Ginseng (Panax Ginseng) - It is important here to remember the 'asian' part of the name as different types of ginseng have different effects. Asian ginseng improves adrenal function and increases blood pressure and energy. In one large placebo controlled study, the subjects taking asian ginseng experienced a noticeable increase in energy and concentration over a 6 week period. Panax ginseng has been shown to have a strong anti-stress effect, reducing high cortisol levels and bringing the ratio of cortisol to DHEA to a more healthy balance6,7. Cortisol has damaging effects when it is chronically raised, these include immune-suppression and nerve cell damage. Typical dosage is 100mg twice per day. If you can't find asian ginseng then 2-3g of dry, powdered root of Siberian ginseng should have a similar effect.
Echinacea - This herb is best known for its immune stimulating activity and has been the subject of numerous scientific studies. However, it is also claimed to have an adrenal stimulating action so may benefit people with low adrenal function. Published support for this is less apparent than that for licorice and ginseng however8. Echinacea is available a a wide range of different forms so it is best to follow the directions on the packaging. It is wise to supplement vitamin C along with echinacea for treating low adrenal function as adrenal levels will otherwise decrease as the glands requirement increases due to the stimulation produced by the herb. 500-2000mg of vitamin C per day should be sufficient.
Relora® - A herbal preperation produced by Next Pharmaceuticals. The company states that 50 plant fractions were screened in the pursuit of the best anti-stress effects. Relora® is a combination of a patented extract of Magnolia officinalis and a patent-pending extract from Phellodendron amurense. Both of these herbs have a centuries long history of use in traditional Chinese medicine where their indications include improving general feelings of wellbeing and balancing blood sugar levels. The combination of the extracts in Relora® produce a supplement with potent stress reducing and adrenal hormone balancing effects by binding to important stress related receptors in the nervous system. Relora® has similar subjective effects on sleep and anxiety as tranquilizer medications such as the benzodiazepines (Valium, Xanax), but without any of the potential side-effects such as sedation and addiction. As such, Relora® is a very effective natural sleep aid. More importantly in the context of this page, studies have shown that Relora® has the ability to balance the adrenal hormones, cortisol and DHEA, moving them away from a stress profile to more healthy levels. In a small trial commissioned by Next Pharmaceuticals, cortisol and DHEA levels in 12 patients with mild to moderate stress were measured. As discussed earlier, raised cortisol and lowered DHEA levels are associated with chronic stress. After 2 weeks of Relora® supplementation at 600mg per day, in divided doses, study participants showed a significant increase in salivary DHEA of 227% and a moderate decrease in morning salivary cortisol levels of 37%. Relora® caused the levels of both hormones to return to the normal healthy range in all subjects during the 2 week trial. Findings from Next's trials regarding the anti-anxiety effects of Relora® have also been backed up by published research from independent researchers13. Relora® has no known side-effects and is reasonably priced. Many 'anti-stress formulas' now contain Relora® as well as other herbs and nutrients.
Hormone Replacement - The most direct way to treat low adrenal function is by taking tablets of the hormones that are deficient.
DHEA - If your DHEA-S levels are low then taking DHEA is likely to produce an improvement in your symptoms. Numerous studies have found DHEA-S levels to be low in CFS patients and also that taking DHEA improves many symptoms of environmental illnesses, most notably fatigue, mood and general feelings of well being9, 10, 11. Many people describe feeling better in general, both physically and mentally. DHEA is available over the counter as a nutritional supplement in the US and can be easily purchased online. Most doctors who use it recommend starting at 5-25mg per day and increasing slowly to the point that feels best to the individual. Doses of 200mg have been used in studies and have shown no significant side-effects in the short-term. Long term data is scarce however, so caution should be used if you take DHEA over a long period. Women should tend toward the lower end of the dosage range whereas men can take more. It is recommended that DHEA-S levels be tested periodically so they don't increase above normal levels. It should be cautioned that DHEA converts into the sex hormones estrogen and testosterone and therefore potentially has the risks associated with an excess of these hormones which include facial hair growth in women and hair loss in men with high testosterone levels and menstrual irregularities in women and stronger expression of feminine characteristics in men when estrogen levels are high. Some doctors also do periodic liver function tests as some studies have shown that extremely high doses of DHEA can cause liver damage in animal subjects. People with existing liver problems should be especially wary of this and should think about using a sublingual form so less is entering the liver at the same time. DHEA supplements have the advantage of being cheap.
7-Keto DHEA - A derivative of DHEA and is said to be safer due to the fact that it can't be converted to the sex hormones testosterone and estrogen. Proponents of 7 keto suggest that at the same dose as DHEA, 7 keto has an equal or even stronger immune enhancing, memory enhancing and stress reducing action. However, clinical studies are lacking at this time so no definitive information can yet be given regarding its effectiveness or safety.
Hydrocortisone - This is the synthetic form of cortisol and is available only by prescription. If your cortisol levels are low then it is worthwhile trying low dose hydrocortisone treatment. Doctors prescribing this this therapy typically use doses in the range 2.5-20mg per day. A number of studies have shown that low dose hydrocortisone is effective for treating CFS in many patients12. Low cortisol levels result in fatigue, low blood pressure, poor immune function (as does high cortisol), hypoglycemia and an increased likelihood of having allergies and chemical sensitivity as well as an inability to deal with stress, to name the most prominent symptoms. It should be noted that the doses used to treat CFS and other environmental illnesses are well below those used in adrenal insufficiency diseases. Many doctors are unwilling to use hydrocortisone for anything other than in cases of full blown adrenal disease as there is a risk takin hydrocortisone may cause the adrenal glands to produce even less of its own cortisol as it's production is controlled by a feedback mechanism. Research on this matter is currently conflicting but it is wise to be cautious and use the lowest dose possible for the least amount of time possible. Hydrocortisone should be taken under the care of a doctor only.
The Adrenal - Thyroid Link
In the early stages of adrenal exhaustion cortisol levels become chronically raised and DHEA levels start to decline. This situation has a negative impact upon thyroid function since cortisol is directly antagonistic to thyroid function. Presumably, this is the body's way of conserving energy by reducing thyroid activity and thus slowing down metabolism. Cortisol reduces thyroid activity by reducing stimulation of the thyroid gland through decreased output of Thyroid Stimulating Hormone (TSH) from the pituitary. It also acts to stop the conversion of the thyroid hormone T4 (thyroxine) into the active form, T3.
Low thyroid function can have a host of consequences for health and wellbeing. To learn more see our thyroid page