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The Biochemistry of Insomnia

by Jurriaan Plesman BA (Psych), Post Grad Dip Clin Nutr

Insomnia can be a most devastating experience. It has been estimated that one third of people suffer from chronic insomnia.

Sleeping problems that last a couple of nights may be due to environmental stress or to excitement. Environmental stress can produce stress hormones, such as adrenaline and cortisol that can interfere with the synthesis of serotonin. When we are dealing with chronic insomnia it is more likely that these stress hormones are produced internally due to a metabolic disorder.

With chronic insomnia, lasting for months or even years, we need to look at the underlying biochemical factors that may contribute to the illness.

Sometimes causes are difficult to identify, but chronic physical pain, medications, even a bad mattress and continuous noise may contribute to sleeping disorders.  See also other health problems.

If we want to treat it we must look at the biochemistry of insomnia, before we can treat it.

The major cause of insomnia is the failure of the body to produce sufficient amounts of the neurotransmitter melatonin. This chemical induces us to sleep in conditions of total darkness. Thus an appropriate dark room is one necessary condition. The bedroom should never be used for reading or watching television. When you happen to go to the bathroom in the middle of the night, try to do so in the dark. Don’t switch on the light as this will switch off melatonin production. Melatonin production also decreases with age. (Source).

The neurotransmitter, melatonin, is produced in the pineal gland from serotonin – our feel good chemical – which in turn is derived from typtophan – an amino found in food. Thus biochemical pathway is

Tryptophan —> Serotonin —> Melatonin

Therefore insomnia is merely a symptom of a wider problem of metabolism. It is interesting to note that the production of serotonin – forerunner of melatonin – is helped along by bright daytime full-spectrum sunlight. It helps to produce vitamin D, one of the hormones produced in the skin and necessary in serotonin production.

Since an imbalance of serotonin is said to be responsible for depression it is obvious that when we have endogenous depression, we are most likely to be suffering from insomnia as well. The two symptoms are related. Because of the serotonin connection it may also be related to anxieties. A decline in melatonin production may also be a function of aging. Mohammad Shafii. Many drug addicts when they withdraw from drugs may suffer from anxiety and/or insomnia as part of the original cause of addiction  — hypoglycemia.

Nutritional sources of tryptophan can be found in “Rich Sources of Nutrients” at Tryptophan .
We could look up food sources of tryptophan to make sure that we have sufficient tryptophan to produce melatonin.

However, unfortunately human biochemistry is not as simple as that.

It would seem that treating insomnia would be the same as treating depression, which aims at getting to body to produce adequate amounts of serotonin as the forerunner of melatonin.

In order to produce serotonin from tryptophan we need plenty of Vitamin B6 (pyridoxine) and Magnesium as well as vitamin D (from sunlight). These are essential coenzymes necessary in the conversion of tryptophan into serotonin and without which the body cannot produce serotonin. If it cannot produce serotonin, it cannot produce melatonin (our sleeping hormone), which is also dependent on vitamin B6 and magnesium. In addition we need a normal source of biological energy called ATP from the normal metabolism of carbohydrates to energise the biochemical conversion tryptophan into serotonin and other biochemical mechanisms. This explains why insomnia is one sign of hypoglycemia.

It is interesting to note that taking vitamin supplements after six o’clock at night might cause insomnia, especially vitamin C and B6, which may be used for detoxification purposes.  For more details on insomnia see Getting off the Hook page 182.

People suffering from insomnia are often prescribed sleeping pills. Some of these may be highly addictive and may even cause the very symptoms that are meant to treat. See drugs causing insomnia.

Natural remedies that are much safer than prescription sleeping pills are:

Valerian: 250-500mg (Start with lower dose)
Melatonin: 1-3mg before bedtime (Start with lower dose, also useful in chronic pain)
St John’s wort: 100mg before bedtime
5-HTP: 100mg 5-hydroxytryptophan before bedtime (Not approved in Australia and New Zealand. Especially useful when taken with vitamin B6 and magnesium)
Calcium/magnesium: 600mg calcium and 600 magnesium before bedtime with food. (Be careful taking magnesium if you have a kidney disease.
Vitamin B6/niacinamide: 50mg B6 and 500 mg niacinamide before bedtime
Chamomile: as a tea, 1 cup in the evening
Kava: 250 mg before bedtime (Standardized to contain 3.5% kavapyrones)
Pantothenic acid (Vitamin B5): 50 mg daily. (good for relieving stress)
Inositol: 100mg daily (Enhances REM sleep
Herbs: California poppy, passionflower, skullscap, catnip

Note that these supplements are also used in depression.

You could also try the use of GLYCERINE.

Most of these supplements should be used one at a time and not be mixed with prescription drugs. Valerian and melatonin can be rotated with St John’s wort. It is always wise to consult a health practitioner when embarking on self-medication. See also: St John’s Wort & Pregnancy.

However, the effectiveness of taking natural remedies is often very disappointing to many people suffering from insomnia.

The reason is that nutritional or herbal supplements – as is the case with pharmaceutical drugs – do not always target the biochemical abnormality that is responsible for the symptoms we are trying to treat.

For instance, if we were to take SAM-e a very well recognized antidepressant nutritional supplement – it could help produce serotonin IF, and only if, we have sufficient amounts of tryptophan, vitamin B6 and magnesium. SAM-e can only supply a methyl group to trigger a change in the shape and function of chemical molecules, i.e., convert tryptophan into serotonin or in the methylation of norepinephrine. The same applies to St John’s wort failure to induce relaxation if the real cause of insomnia is a tryptophan deficiency or B6 deficiency.

The body can produce its own SAM-e (S-Adenosylmethionine). It is present in every cell of the body and is derived from methionine in the presence of vitamin Vitamin B12 and Folic Acid, plus a molecule of biological energy (ATP). ATP is the end product of glucose metabolism and without that energy the body cannot manufacture the neurotransmitters necessary in sleep.

When the brain is threatened with energy starvation it will send a hormonal message to the adrenal glands to pour adrenaline into the system. Adrenaline is a hormone that converts glycogen – strings of glucose molecules stored in the body – back into glucose, so as to feed the brain again. (See image). But abnormal adrenaline secretion during the night can also cause insomnia and nightmares.

However, if the body has a deficiency of Vitamin B3 (Niacin), all the available tryptophan in the body may be used up in the conversion of tryptophan into niacin, leaving little for conversion to serotonin.

When there is a niacin deficiency tryptophan is converted to vitamin B3 at the ratio of 60 to 1, which may create a tryptophan deficiency despite adequate amounts in food !

The supplement of niacin alone has miraculously cured depression in some people.

It is said that many biochemical reactions need vitamin B6 (pyridoxine), but this vitamin, which is obtained from food, needs to be converted to an biologically active form (pyridoxine-5-phosphate or P5P) before it can be used in biochemical reactions. The enzyme converting vitamin B6 to P5P is via a zinc dependent enzyme (pyridoxine kinase).

Thus when the body is deficient in zinc it cannot utilize vitamin B6. Therefore, a zinc deficiency may also cause depression and insomnia.

Many prescription antidepressant drugs interfere with the natural synthesis of serotonin by inactivating vitamin B6 (pyridoxine). This causes a virtual B6 deficiency affecting many other biochemical reactions. With abnormal serotonin levels some AD medications can affect the appetite centres in the brain, creating weight problems.

Zinc is a mineral that is absorbed across the gut membrane if it is combined with picolinic acid. This is produced from tryptophan in the pancreas under the influence of vitamin B6. Thus there is an interdependency between vitamin B6 and zinc.

To complicate matters further all these chemical reactions are dependent on sufficient amounts of biological energy (ATP). For example, the effectiveness of SAM-e is dependent on biological energy and without ATP, SAM-e cannot be synthesized.

Thus people with hypoglycemia – which may be seen as a disease of energy production – are not likely to have sufficient ATP or SAM-e to carry out the necessary biochemical reactions to produce serotonin and melatonin. This explains why insomnia is one of the common symptoms of hypoglycemia.

We also need to take into account that food sensitivities and environmental allergies can affect serotonin production. See: Allergies: the Food and Disease Paradigm by Dr George Samra.

A healthy human biochemistry depend on many nutritional factors, too complex to be handled by single magic bullets like drugs or single nutrients. This theme has been further explained in “Hit or Miss Supplements for depression

Yet, the solution is so simple!!!

If the major cause of insomnia is the hypoglycemic syndrome, then this can easily tested by a special medical Glucose Tolerance Test for Hypoglycemia (GTTH). Hypoglycemia or a suspected nutritional abnormality can also be tested by a paper-and-pencil test called the NBI. Another test is at:   Hypoglycemia Questionnaire

If we are able to supply the body with all the nutrients, enzymes, coenzymes, vitamins and minerals, it will have all the ingredients to synthesize the necessary neurotransmitters and hormones that can make us feel happy and content when we should. A natural diet should provide us with all the components to build the necessary serotonin and melatonin to enable us to sleep.

The hypoglycemic diet works because it is a natural diet, that humans have consumed normally for eons of times, AND it is especially adjusted to the modern problems of hypoglycemia – a common element among depressed people – in that it aims to normalize blood sugar levels, insulin and stress hormone levels.

The era of indiscriminate drug taking for insomnia should belong to the past and patients need to educate themselves on the connection between insomnia and nutrition, if they want to really solve their emotional problems for good.

When you have been taking sleeping pills of any kind you can only withdraw from these under the supervision of your doctor. By gradually reducing the dosage over time the Hypoglycemic Diet will ease the withdrawal symptoms.

Medications causing insomnia are: Bronchodilators, Anti-Parkinson drugs, Zoloft, Prozac, Paxil, Celebrax, Zebata, Provachol. Norvasc, Caffeine, Excessive alcohol use, tobacco, caffeine, amphetamines, thyroid hormones, certain weight loss drugs, Phenylpropanolamine (PPA), nasal decongestants, diuretics – due to night urination, some high-potency vitamins especially after 6 pm i.e., vitamin C. And many more. Source.

Please discuss this article with your health care worker, doctor or nutritional doctor or therapist.

Also read:
What is Hypoglycemia?

The Hypoglycemic diet

The Serotonin Connection

Hypoglycemia- is it a cure-all for mental illness?

Hit or Miss Supplement. for depression

Depression: a Disease of Energy production.


19 Responses

  1. Very well put together summary thank you Jurriaan

  2. Tired of This says:

    Your following quote is quite ridiculous, it implies we are not “allowed” to stop taking any over the counter sleep aid without going to see the “doctor”. If that were true, nobody would ever stop taking valerian, etc without first paying someone ingnorant in natural sleep aids for their “expert help” in “withdrawing”:
    Your page erroneously states “When you have been taking sleeping pills of any kind you can only withdraw from these under the supervision of your doctor” Ha.

    • Jurriaan Plesman says:

      We are referring to serious mind altering drugs. 
      It is medically advisable that when you are addicted to pharmaceutical tranquilizers or  illegal drugs to withdraw from them under the supervision of a doctor. 
      It is possible to withdraw from drugs without medical supervision, but there certain risks attached. to this. 
      No responsible counselor would suggest to a client to withdraw from psychotropic drugs without the help of a doctor. Detoxification can have serious medical consequences. 

  3. Jessica says:

    I have been sleeping fine lately until I started a multi vitamin, mainly b vitamins. I have been taking them for one week and have no not slept for two days and still don’t really feel tired. I have been reading research that suggest taking vit b6 has been linked with chronic insomnia in some people (with some individuals up for days at a time of 5mg). Was wondering what you’re thoughts on that was? 🙂

  4. Jennifer says:

    For Jessica; I have to take my B Vitamins with breakfast or lunch. Any later in the day, and it disrupts sleep. So try taking your new vitamins earlier 🙂

  5. Badley says:

    i’m an iraq war vet diagnosed with psychosomatic insomnia and narcolepsy without cataplexy due to possible ptsd. i currently take amitriptyline 50mg and seroquel 100mg nightly for sleep. sometimes it doesn’t even make me sleepy. without the medicantions i wake up on average 12-15 times in an eight hour period, 4-6 with medication. i found this article very interesting and would like to give it a try. i would really like to at least be able to cure my insomnia, although i’ve been struggling with this for over 2 years. i’ve tried taking 3 10mg melatonin pills the past few nights with the amitriptyline to fall asleep (i forgot to fill it in time for the weekend) but i feel nothing. do you think it may work, or am i an extreme case?

  6. chris says:

    do you recommend seriphos for night time cortisol reduction and its effect on the tryptophan serotonin melatonin effect?.
    you say niacin can miraculously cure people of depression but why not insomnia?..

    • jur says:

      I am not familiar with serifs, but if this is a drug then i suggest you discuss this with a doctor. Niacin is certainly involved with serotonin production from tryptophan. Whatever helps the production of serotonin, helps the production of melatonin, the sleeping hormone.

  7. chris says:

    i also noticed worsening insomnia after taking B 6 (after breakfast!)(as pyrodoxine hydrochloride) and that i couldnt go back to sleep like i used too after waking after 3 hours or so…my theory is that this is a very poor form of b 6 that somehow interferes with the needed conversion of b 6 to pyrodoxal 5 phosphate the zinc based enzyme that is needed for serotonin/melotonin and good sleep..

    my insomnia improved after supplementing with sublingual 5000mcg methyl B12 and methyl folate(i was severely deficient in b12(146) after being vegan for years and proper b12 levels are needed for production of melatonin..at one point before starting the methylation therapy i was waking after sleeping just one hour and could never get back to sleep until getting my b12 normalised, which meant i could go back to sleep after waking and sleep a total of 4-5 hours of much more restful sleep than before the b12 therapy.

    sleep deprivation stress will cause one to lose zinc rapidly and as i also need alcohol to put me to sleep and am a vegetarian this means i am likely zinc deficient(lost my sex drive also and zinc is needed for testosterone) so i have started supplementing with zinc picolonate at 50-75 mg daily…hopefully as my zinc builds it will mean i can convert B 6 properly with the needed P-5-P zinc based enzyme and so create sufficient serotonin/melotonin..

    i may also be B 6 deficient so i have just ordered some pyrodoxal 5 phosphate supplements and as i wont need proper zinc levels for this already converted B 6 to work i am curious to see if it amps up my melotonin and finally cure my insomnia of 15+ years.

    i hope what i say can help others in remedying their insomnia..

    thank you jurriaan for this intelligent article,it has been very helpful to me.

  8. Citrine says:

    Thank you for publishing this online for all to see. With longstanding secondary insomnia I have been frustrated by the overly simplistic things I read or hear from most medical folks that seem to want to explain away the problem with one “cause”. I’ve wanted to understand the chemistry involved and this is the most comprehensive thing I have seen. I am going to pursue the hypoglycemic route. Being post-menopausal – and this was the onset of the insomnia – I wonder how this enters into the picture. The insomnia stats for PM women is staggering and it is not just about hot flashes.

  9. solid says:

    is melatonin the only hormone that regulates sleep. i read elswhere that cortisol also plays a vital role.please can you let me know of any other hormones thta can have an effect on insomnia and how they do so?

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