In cases of cortisol insufficiency; therapies (including nutritional and herbal therapies) that would normally improve physiological function are often counterproductive, due to a failure to adapt properly to these therapies. 

It is very common that if cortisol output is lacking, another hormone, aldosterone, also made in the adrenal cortex is often insufficient. Aldosterone helps maintain adequate blood pressure by preventing excess loss of salt and other minerals into the urine. Aldosterone deficiency can be resolved with the use of suitable doses of liquorice. However, it is unwise to supplement with both cortisol and liquorice for more than two to three weeks as this renders it difficult to estimate the actual amount of cortisol produced over a 24 hour period. This is discussed in the full notes linked above. 

For marked adrenal insufficiency or a crisis/acute emergency situation it is wise to start with actual cortisol supplement first (Adrenal MAX Support +), and later experiment to see if one can move over to liquorice supplementation.  Also regular use of liquorice at doses higher than 1.5g daily (equivalent to 1 capsule of Adrenal Boost +) in some people can raise blood pressure higher than normal. Those suffering from excessively high blood pressure are advised not to take liquorice. 

Regular home testing of B.P. is recommended. 

Full spectrum salt like Celtic Ocean Sea Salt can help balance blood pressure; increasing low blood pressure and often lowering high blood pressure.

 

Topics discussed in this update are as follows....

When we stand up, those of us who are in good health experience a rise in blood pressure after one minute, or at least no significant drop. In contrast, adrenal fatigue sufferers will see a fall. In very general terms, a larger drop in blood pressure signifies a more severe case of adrenal fatigue.

Use only cuff blood pressure type monitor. 

Orthostatic hypotension (blood pressure dropping when comparing B.P. from lying position to standing) can be confirmed by measuring a person's blood pressure after lying flat for 5 minutes, then stand up and take B.P. reading again 1 minute after standing, and again 2 minutes later (still standing) Keep the B.P. cuff on left arm and when taking standing readings hold arm straight out (you may need to support it with something if muscles are tired) so that it is at the level of the heart.

Orthostatic hypotension is defined as a fall in systolic blood pressure (The first figure e.g. 130/XX) of at least 20 points and/or in the diastolic blood pressure (The second figure e.g xx/60) of at least 10 points between the lying down reading and the upright readings. In addition, the heart rate should also be measured for both positions. A significant increase in heart rate (e.g more than  30 beats per minute increase) from lying down to standing (with little drop in B.P.) may indicate a compensatory effort by the heart to maintain cardiac output or postural orthostatic tachycardia syndrome (POTS). 

If there is orthostatic hypotension it is indicative of some degree of failed response to the need for more blood to the brain when standing and suggests investigating the appropriateness of cortisol, or liquorice and full spectrum salt supplementation along with eliminating any chronic dehydration. It is unwise to try and drink more water than normal, especially in this situation without concomitantly making sure salt intake is to your needs.  For discussion of appropriate salt supplementation see celtic salt article here

There are many causes of postural hypotension, including dehydration to heart disease. If the person has had auto-immune disease of any kind excessive inflammation, asthma or chronic fatigue then it is highly likely that supplementation with cortisol (Bio-identical hydrocortisone) at safe physiological doses or aldosterone support with Liquorice will help the overall health of the person. 

These are only approximate guides and of course we must take into account the overall weakness and fatigue or otherwise of the person. Ultimately at some point a saliva cortisol (24 hour sample(s)) should be taken and compared with BP readings taken on that day to get a confirmatory reference.

We hope to be able to offer a cost effective cortisol saliva test (for less than the typical cost of £40 for mail order cortisol saliva tests) in the latter part of 2017. New technology is about to be released; a fairly simple device that one can use to measure saliva cortisol at home. These devices have not been priced yet, probably somewhere in region of £100 and and about £7 per test consumables. The device will need to be connected to a recent Android tablet or Phone or an Apple iPhone 6 or later. We await further details at the time of writing (April 2017). We hope to be able to offer the testing service and the devices from about July 2017. To register early interest please email j@rnemail.com 

These include....

Mental and psychological ailments such as depression

Faintness and dizziness

Weakness and fatigue

Heart palpitations

Emotional hypersensitivity

Inability to cope with stress

Social anxiety

Muscle weakness

Headache, scalp ache, or general body ache

Severe or dull lower back pain

Extremely sensitive skin

Nausea, diarrhea, and vomiting

Abdominal pain and hunger pain despite an empty stomach

Craving for salty foods

Anxiety and jitters

Clumsiness and confusion

Motion sickness

Insomnia and dark circles under the eyes

Low bladder capacity and symptoms of IBS

Irregular or non-existent menstrual period

Difficulty getting out of bed each morning 

Constant tiredness and fatigue 

Inability to handle stress and stressful situations 

Feelings of being overwhelmed by events 

A lack of enthusiasm for things or events that were previously exciting 

cravings for sugary snacks 

Low energy levels in mornings 

A need to take a nap or rest in the afternoon 

Higher energy levels in the evenings, especially the late evenings 

Lying awake feeling "buzzed” at night, unable to sleep 

Regular cold viruses and/or a weakened immune system 

Asthma, allergies or respiratory complaints 

Dark circles under the eyes 

Dizziness 

Dry skin 

Extreme tiredness an hour after exercise 

Frequent urination 

Joint pain 

Lines in your fingertips 

Loss of muscle tone, or an inability to gain muscle 

Persistently low blood pressure 

Frequent low blood sugar 

Lack of libido, low sex drive 

Lower back pain 

Numbness in your fingers / Poor circulation 

Weight gain (especially abdominal) Anxiety?Panic attacks?Low thyroid function 

Brain fog 

Over-dependence on coffee to get through the day 

Intolerance of hot or cold temperatures 

Inability to focus or concentrate 

Psoriasis 

And.....ANY AUTO-IMMUNE DISORDER !

Of course, these symptoms won’t all occur simultaneously, or immediately. Some people suffering from low cortisol will experience a couple of these symptoms, perhaps one after another. If you experience any one of these, or a combination of them, severely enough that it is affecting your day to day quality of life, you should RECTIFY THE SITUATION. Failure to do so can be life threatening in some situations. Examples include: If you encounter unusual stress such as long haul flights, relationship problems, death of spouse etc that will demand more cortisol. If your adrenals are already struggling to produced the non-stressed daily cortisol need (about 40 mg) a stressful time/situation can need as much as 100 mg or more daily and your adrenals on this demand can and often will shut down and hardly produce any. In that situation a pre-existent health problem such as auto-immune tendency, asthma can suddenly flare up and become an emergency. Also just a common infection such as influenza demands high amounts of cortisol for the body to fight it. Without adequate cortisol during such an infection the result could be death.

This means that the regulating anti-inflammatory effect of cortisol is absent. Without sufficient cortisol, there is nothing to prevent severe, chronic inflammation. In effect, the immune system is running out of control. Low cortisol leads to increased production of pro-inflammatory cytokines, which lead to an over-activation of the immune system and inflammation. According to Dr. Thomas Guilliams, an immunologist, "The result is amplification of numerous inflammatory pathways and increased susceptibility to developing inflammatory diseases, including autoimmune diseases, mood disorders, atopy, malignancy, chronic fatigue syndrome, chronic pain syndromes, obesity, glucose dysregulation and fibromyalgia.

Cortisol releases glucose from the liver; this is used by all the cells of the body to provide the main fuel for the cells to make ATP. ATP produces most of the bodies energy for survival, regulation and homeostasis.

The circumstances and diseases that trigger low cortisol, or hypoadrenalism, vary. Besides the autoimmune disorder Addison’s disease, other causes include secondary hypoadrenalism, or a deficiency of ACTH. Secreted from the anterior pituitary gland. Tendency to produce inadequate amounts of cortisol can be genetic or constitutional e.g. acquired early in life due to poor mother or baby nutrition/vaccinations. Low cortisol output that occurs later in life can be brought on by long periods of excess cortisol production due to excess stress that 'tires' the adrenal cortex to the point of chronic insufficiency. Stresses can include serious infections, poor lifestyle, not enough sleep, to much work , combined with EMF stresses and so on.

Introducing energy therapies, energising nutritional supplements, energising herbs and even grounding minerals often has adverse effects on persons with low and especially very low cortisol status. This is because cortisol is the hormone of adaptation or change. Any activity in the body, any shift of energy, in fact any function of life requires some cortisol. The more potent the potential therapeutic input the more the body is pushed to up-rate its energy and systems as life is energy and activity. Without adequate cortisol the body is unable to cope with new or even existing energy and activity, whether it is internal physiological activity or external physical activities like talking, walking watching tv and so on.

In practice, many with below par health find they are rather sensitive to therapy inputs so have to proceed slowly when adding in supplements and keep doses low or very gradually increase dose. Also, energy therapies need to be gentle and of shorter duration than most persons.  These types of individuals usually have mild to moderate cortisol insufficiency, although they may be unaware of this fact. Supplementing with cortisol to the correct physiological needs is perfectly side effect free on a long term basis, unlike the indiscriminate overdosing of artificial cortisol that have been used by Doctors that has given cortisol and its patented derivates a bad name.

There are many struggling with long term health problems and no mater what therapy they try, they fail to get well, typically the chronic fatigue cases and the  auto-immune cases. This is simply resolved by supplying the correct amount of cortisol the body needs on a daily basis. To some extent and certainly with experience of the patient this can be ascertained with the Postural blood pressure test.

Cortisol tests by laboratories are expensive and not reflective of the varying daily needs. There is soon to become available a device that enables home cortisol testing. The device will be in the order of 100 GBP and needs to be connected to a i-phone or android tablet, possibly more devices will be enabled soon. Each test done at home uses disposable materials that work out about 8£ per test.

This is an improvement on current saliva cortisol assay tests that have to be sent away at about £25 to £50 per single test. We hope to offer the devices or the cheaper testing service from about July or August 2017.

Adrenal Boost + a high potency liquorice supplement

It is common that if cortisol supplementation is required there will also be a need to improve another adrenal hormone called aldosterone. This hormone is to regulate the amount of salts and other minerals that should be kept in the body or eliminated via the urine.  If the pH of the urine is checked e.g. while we are dependent on cortisol (or at any time out of interest) and found to be too alkaline on a few successive days, this can be an indication the body is loosing too many salts and minerals. This, if continued is damaging to health overall, especially in the long term. The most fundamental protector of long term health is to maintain a good mineral store and balance and closely associated with that is correct acid / alkali (pH) balances in the body. We take in minerals via food, especially fruits and vegetables and good quality full spectrum salt. To loose these minerals excessively via the urine is a tragedy.  

Personally, I found that for the first few weeks of taking 20 mg cortisol daily the urine pH was too alkaline, however the urine pH returned to normal without introducing liquorice. This may be due to the overall therapeutic effect of cortisol and its side effect of taking stress of the adrenals allowing them to recover their aldosterone secretions.

We can support the aldosterone pathways/chemistry simply with Liquorice herb. Liquorice also acts to help the adrenal cortex produce cortisol and also helps in cortisol retention in the body. So once we have been supplementing with cortisol for a suitable time period, i.e when we have come out of any crisis of insufficiency i.e. acute asthma or other auto-immune flare up, we can see how we get on with replacing  cortisol supplementation with Liquorice. This may return the pH of the urine to our normal base line, i.e. a more acid state indicating we are no longer loosing excessive salts and minerals. 

The world expert on what the pH of urine and saliva should be for a healthy well mineralised individual who studied this for many years and had high success rate in his clinics with thousands of patients is Dr Carey Reams. He established that a healthy pH is 6.4 for both urine and saliva, although if we are actively improving mineralisation it can rise to around 6.8 for both urine and saliva. Having the urine and saliva pH the same is the ideal, if they are deviant this suggests all is not yet in balance.  

The reason for having slightly acid saliva and urine pH is that the process of breathing and metabolism of food is acidifying and this is reflected in the urine and saliva. The pH of the blood is /must be maintained at around 7.34. If insufficient minerals are taken in to neutralise proteins and various stresses of life and metabolic activity, minerals are drawn form the bones and tissues to keep the blood pH near as possible to 7.34. Long term over acidity of the tissues,  (this can be picked up with urine and saliva readings below 6.2 more severe into the 5's ) results in low oxygenation and excess free radicals (+ charges) that provide the breeding ground for cancer , diabetes and most other chronic disease.

pH values of urine and saliva do vary over the day , before and after meals. However the more stable the pH readings are, indicates that the mineralisation of the body and homeostasis in general is on track.

Taking a urine and saliva reading first thing every morning and or at night will over time give one a good guide to how one is doing.  Not all pH papers are of a suitable range or accuracy recommended Ph papers are pH Hyrdron  see here.

The reason Liquorice can raise Blood pressure is that it helps via aldosterone pathway to retain minerals especially salt from being excreted via the urine. Usually for adrenal insufficiency cases this is a good thing as it can help raise excessively low blood pressure, ensuring all the cells get and adequate pressure of blood, therefore nutrients and oxygen. The role of salt in blood pressure management is seemingly contradictory, but in reality full spectrum salts are balancers of blood pressure. One of the most successful ways of reducing consistently high B.P. is to take a full spectrum highly mineralised salt such as Celtic Salt for full extensive information on why we need salt for health see here.  On the other hand excessively low blood pressure can be raised with the correct amounts of Celtic salt (and or liquorice but make sure you have sufficient salt)

When it comes to normalising pH the best most balanced and sustainable way to achieve this is with a fluid that has the same pH as the blood around 7.4 and an almost identical minerals and trace minerals profile of the ideal extracellular fluids in our body (about 22pints in the average individual) This is a liquid or mineral matrix from where our cells first evolved, the sea. So by taking a pure pollution free inland sea water concentrate in the correct way daily will act as the most homogenous and powerful pH buffer available. For detailed information see here

In some cases of adrenal insufficiency it may be possible to come off cortisol and maintain cortisol output with the aid of sufficient doses of liquorice and vitamin B5/pantothenic acid alone. However, one has to be vigilant in checking ones symptoms, B.P. lying then standing readings on a long term basis, and if possible obtaining salivary cortisol tests periodically. 

After time it is normal to loose vigilance but it is best to regard the truth, if one has been adrenal deficient regarding cortisol production this is often a lifetime issue. It's one thing to be able to to support the adrenals with liquorice and B5 and have normal cortisol levels in an unstressed situation. This requires about 40 mg a day of  adrenal cortisone production. Don't assume your adrenals are competent as stressful situations such as infections, relationship or financial problems, long haul flights, excess worry, work, not enough relaxation and sleep, can  trigger almost total cortisol failure on demand.  If you adrenals are only capable of producing 40 mg daily and suddenly the demand is on to produce 100 mg daily, it can exhaust the ability of the adrenals to produce even 40 mg cortisol, so production may fall to very low levels and this is in a stress full situation!  This happened to me and I ended up in the emergency room being pumped with oxygen and bronchial dilators for 2 days just because I thought I no longer needed to take cortisol above meager levels.  Blood test taken at the time revealed I had only about 1% of the normal cortisol levels. (This was after taking 100 mg cortisol that day, as the auto-immune crisis with rampant inflammation was absorbing cortisol faster than It could, in one day keep up with)

So the reality is we have two levels of cortisol support: Unstressed levels, typical adult needs are around 40 mg daily if the adrenals are unable to produce any significant amount) and stressed levels e.g. in a cortisol demand crisis typically 100 mg daily for up to 7 days (that would not have happened if we had immediately upped cortisol levels to that required eg 100 mg  prior to the full blown crisis for a few days)

Note : Artificial cortisone medications that closely mimic the naturally produced cortisol are more potent per milligram. E.G. prednisolone  is approximately 4 times the potency as the cortisol supplement sometimes called hydrocortisone or bio-identicle hydrocortisone.  So for example, 10 mg prednisolone is equivalent in potency to 40 mg cortisol. If you cannot obtain the cortisol/hydrocortisone soon enough from here prednisolone prescribed by Doctor can be used on a temporary basis.

Cortisol supplementation as indicated is perfectly safe in the  long term if we do not consistently exceed physiological NEEDS. If a person has no ability to produce cortisol  then 40 mg daily is the unstressed amount required. In practice, most long term adrenal insufficiency cases can produce some e.g. in the range of 5 to 30 mg daily, a common support is around 20 mg daily in unstressed situations. There is a feed back mechanism via pituitary hormones so that e.g. if one where to take 30mg daily and one only needed 10 mg daily supplementation in that unstressed situation, the feedback mechanism would tell the adrenal cortex to produce less resulting in the required total of 40 mg daily.  If one supplements e.g. at 30 mg daily then the cortex still has to produce some, so avoiding the adrenal cortex from getting too lazy. If 40mg cortisol daily is taken but the adrenals can still produce some, this would not be a good idea in the long term as the adrenal cortex would become de-conditioned i.e lazy and if cortisol supplementation where stopped suddenly there could be a state where almost no cortisol would be produced, i.e a wean off period would be needed.

In fact according to the worlds expert on cortisol Professor William Jeffries The Safe Use of Cortisol supplementing with cortisol to a little below the bodies needs, so that the cortex only has to produce a little cortisol give the adrenals  time to rest and recover form previous excessive strains and exhaustion.

In the vast majority of cases these people will not be producing enough cortisol to maintain health/homeostasis. It is usually unproductive to take any course of therapeutic input be it energy therapy or nutritional supplements (except for the most gentle, gradual inputs of non-stimulating remedies and full spectrum salt) as any 'move' within the persons physiology to improve energy will demand more cortisol that is simply not available. In such a situation the engendered increased need for cortisol or the gap between the physiological demand and the actual cortisol output produced by the adrenals will be widened. This will cause a worsening of the disorder as the immune system deepens and expands its inflammatory attack on the vulnerable areas of the body such as the gut, the brain, the muscles and any susceptible organs such as the heart. It is on this basis that I say cortisol status MUST be rectified by supplementation BEFORE any other therapeutic input for chronic fatigue and to be monitored and if need be, raised on an ongoing basis always preventing a gap between available circulating cortisol and physiological demands on a daily basis. This approach can save years of disability.

Once cortisol levels in the chronic fatigue sufferer are normalised a picture will emerge of the post cortisol supplementation health level (don't forget pH and the liquorice aspect)  The common issues of mitochondrial insufficiency , infection, and toxicity can then be dealt with over a sufficient period of time to restore full health if required.  For my article on Chronic Fatigue syndrome see here

For the previous extensive article on this subject with references and quotes from other researchers see here

Warning: Make Sure you do not cause excess cortisol by taking Adrenal MAX Support + AND Adrenal Boost +

Ideally we should have a 24 hour saliva cortisol test if taking Adrenal MAX Support and even regular high dose i.e more the 3 capsules daily Adrenal Boost on a regular basis. However  this is not foolproof as some people have cellular cortisol resistance so a salivary or blood test can read high but the cells may not be getting enough. In the words of the foremost world expert on Safe Uses of Cortisol Professor William Jeffries a patient trial with taking cortisol to see what the response is, is the only sure way to tell if it is helpful.

If a person where to take more than the physiological needs for cortisol i.e. more than 40 mg daily in unstressed situations on a regular basis e.g more than about 2 weeks, this is not good or healthy, as it would upset the bodies regulation of other hormones and balances, most obviously insulin would rise above beneficial levels and  along with that with have a path towards obesity, syndrome X and eventually insulin resistance and further on leading towards the development of diabetes. That is why chronically stressed individuals who do not succumb to adrenal fatigue (cortisol deficiency as adrenals become exhausted) have raised levels of cortisol over a 24 hour period each day and this in turn raises insulin.

If a person takes liquorice as well as cortisol i.e Adrenal Boost and Adrenal Max, a strategy I have used sometimes to wean off cortisol and eventually just take the Adrenal Boost for the reasons previously discussed, (re aldosterone) it complicates the monitoring of safe dose. This is due to the fact that the normal breakdown and elimination of cortisol in the body is slowed and preserved by the use of liquorice. Also Liquorice can help the adrenal cortex to make cortisone. Normally the level of cortisol in the blood should be high first thing in the morning when we get up and drop down to much lower in the evening and especially in the middle of the night. Taking liquorice and cortisol can render the levels of cortisol in the blood higher than ideal even though one is taking an amount less than 40 mg daily of cortisol. So this throws us back to the question of how can we ascertain if we are have too much or too little cortisol in our system. 

Details have been given about the orthostatic blood pressure readings than can indicate if a person has adrenal insufficiency, however, as we supplement with cortisol and or liquorice the blood pressure orthostatic readings improve, but may not quickly return to absolutely no drop, even though e.g. after a week or so our cortisol blood levels may be adequate.  So as we come up in cortisol status we need more sensitive ways to monitor if we have too little or too much cortisol in our system.

There are many symptoms that MAY reflect cortisol excess but many of these can take weeks months or years to manifest. I noticed that after taking adrenal max and Boost for about two weeks (40 mg cortisol and  2 to 4 adrenal boost capsules) as a come down from an emergency situation I was in when I was taking 100 mg daily of cortisol for 7 days due to auto-immune crisis (asthma) in the face of almost complete failure of adrenal cortex to produce any significant amount of cortisol  I rapidly found my way back to health.

However I was having unusual difficulty in getting a full nights sleep, only getting about 5 hours and rarely feeling sleepy in the evening. My normal pattern is to need /obtain 7 to 9 hours sleep nightly with a relaxed sleepy feeling around bedtime. Cortisol levels normally do and should drop down to low levels around bed time, as cortisol is related to activity and lower levels are needed at night to promote sleep. So having difficulty in unwinding and getting sufficient sleep can be one of the most obvious and immediate signs of cortisol excess, although there can be other reasons for this. 

Reducing my cortisol intake to 20mg in the morning only and continuing with 4 adrenal boost daily solved the sleep issue and proved there was excess cortisol in my system when on the higher dose of 40 mg daily + 4 adrenal boost capsules (liquorice concentrate)  as liquorice reduces the normal breakdown of cortisol in the system. Shortly after this I stopped taking adrenal boost so I could more easily monitor safe cortisol levels. At some time in the future I can stop cortisol and just take liquorice (Adrenal Boost) to see how I get on with that, but always ready to switch back to cortisol if any signs of cortisol deficiency develop as determined by my unique symptoms of chest tightness, allergic symptoms, (plus orthostatic hypotension.) Any stressful situations will need to be monitored carefully.

This sleep problem related to high cortisol levels is well recognised and an inability to relax and wind down in the evening or when one should be tired are all part of that:

While there is no single cause for insomnia, recent studies suggest stress and the body’s inability to control the adrenal hormone cortisol may be a major contributor. Cortisol is a trigger of the stress response, and is accountable for the ‘fight or flight’ feeling we have during stressful situations. Cortisol plays many positive roles in the body, but it also arouses us and wakes us up, and blood levels of cortisol rise between 50 to 160 percent within the first thirty minutes of waking. For the insomniac, however, blood levels of cortisol remain stuck on high and build up in the body instead of being regulated by restful sleep. So the insomniac’s brain is in a constant state of arousal, the result being fragmented, restless sleep, trouble falling asleep and more frequent awakenings during the course of the night.

Below are some symptoms that MAY, but not always indicate you may be producing excess cortisol. This is not relevant to people who are in marked adrenal insufficiency who are not taking liquorice and or cortisol. However some writers state that in the first stage of adrenal insufficiency excess cortisol production occurs, this is confusing as it is not insufficiency but excess, or dysregulation where cortisol levels swing up and down excessively. A common cause of Adrenal insufficiency is being in stressed /excess cortisone state for years, this exhausts the adrenal cortex resulting in a failure of cortisol production at sufficient levels to maintain health. Another trigger can be infection such as glandular fever or a serious case of influenza in susceptible persons, and as infection places great demands for cortisol production. This can be the "straw that broke the camels back” for some persons leading to adrenal insufficiency and often, on from than, chronic fatigue syndrome. 

Sleep problems.

Cortisol stimulates the appetite and cravings for sweet calorie dense foods and high crab food. So if you have high levels of cortisol in your body over a long period of time, the chances are you are going to want to eat fatty and high calorie food.

The symptoms of high cortisol develop gradually and mostly overlap with many other conditions and include

    Depression

    Fatigue

    Weight gain, especially in the face, upper back ("buffalo hump”), and torso

    Obesity, especially abdominal obesity/central obesity

    Back pain

    Thin skin

    Decreased concentration

    Swelling in the hands and feet

    Low libido

    Acne

    Impaired memory (especially short term)

    Female facial hair or female balding

    Insomnia

    Poor skin healing

    Irritability

    Menstrual abnormalities

    Blood sugar dysregulation/high blood sugar

    Decreased bone mineral density

    High blood pressure

    Easy bruising

    Muscle wasting and weakness of arms and legs

    Reddish purple streaks on skin

Certain conditions are well known to cause the types of chronic physical and psychological stress which damage the HPA axis and lead to high cortisol levels. These conditions, which are often associated with high cortisol symptoms, include

    depression

    panic disorder

    generalised anxiety disorder

    post traumatic stress disorder

    anorexia nervosa

    bulimia nervosa

    alcoholism

    diabetes mellitus

    severe obesity

    metabolic syndrome

    polycystic ovary syndrome (PCOS)

    obstructive sleep apnea syndrome

    shift work

    end-stage kidney disease

    major life stressors

    chronic pain