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The Serotonin Connection

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

I will attempt to describe briefly The Serotonin Connection as asequence of psychological and biochemical events in the development of emotional disorders. Most of the statements below can be verified by scientific studies, but some are still controversial, especially the relationship between insulin resistance and absorption of amino acids. Much research needs to be done in this area. The events appear to follow a predetermined sequence as follows;

1) An extended period of physical or psychological stress, will produce stress hormones such as cortisol and adrenaline, that can interfere with the synthesis of the brain neurotransmitter, Serotonin.

2) A neurotransmitter is any one of numerous chemicals that occupy the gap (synapse) between two or more nerve cells (neurons) and thereby allows the triggering of a tiny electrical currents in adjacent cells. Each neurotransmitter fits into a unique receptor – like a key fitting into a lock – thus allowing messages to be carried along nerve pathways. See Figure 1



Figure 1

3) Serotonin is a neurotransmitter that conveys the positive sensations of satiety, satisfaction and relaxation. It regulates appetite and when converted to melatonin helps us to sleep.

4) A deficiency of Serotonin in the brain can cause endogenous depression, upsets the appetite mechanism and may lead to obesity or other eating disorders such as anorexia and bulimia nervosa and may be responsible for insomnia. Doctors usually prescribe Selective Serotonin Reuptake Inhibitors (SSRIs) which have the effects of increasing the amount Serotonin and thereby medically treat the above conditions. Unfortunately, SSRIs may have side effects in some patients, and generally do not address the underlying biochemical causes of depression.

5) Serotonin is produced from an essential amino acid (protein unit), called tryptophan, obtained from food and then converted to Serotonin under the influence of vitamin B6 (Pyridoxine) and magnesium. “Essential” amino acids are sources of protein, that the body cannot produce and must obtain from food!

6) If there is a deficiency of vitamin B3 (niacin),the body will use dietary tryptophan to synthesize niacin. It takes 60 mg of tryptophan to produce 1 mg of niacin. Hence, niacin deficiency may also be responsible for depression.

7) The absorption of tryptophan competes with the absorption of other amino acids in the digestive process.

8) The absorption of tryptophan can be accelerated by consuming refined carbohydrates, such as sugar.

9) Sugar consumption stimulates the body to produce insulin, a hormone which transports glucose, fatty acids and amino acids (except tryptophan) into body cells. Thus insulin speeds up the absorption of amino acids other than tryptophan.

10) This leaves tryptophan available for absorption and conversion to Serotonin (via 5-hydroxytryptophan, 5-HTP) in the presence of vitamin B6 and magnesium, and presto we feel happy.

11) A person low in Serotonin will be inclined to consume greater amounts of sugar in an attempt to increase Serotonin production and this may lead to sugar addiction.

12) Sugar addiction can lead to insulin resistance. High levels of insulin cause receptors for insulin to shut down by means of ‘down-regulation’.

13) Insulin resistance starts first as mild insulin resistance leading to hypoglycemia (low blood sugar level also called ‘hyperinsulinism’), then reactive hypoglycemia, more severe insulin resistance which causes unstable concentrations of blood glucose, and finally more complete insulin resistance, causing diabetes over time. Thus there is a range of insulin resistance from low to severe which causes erratic and unpredictable sugar levels in the blood and to the brain. This explains some of the variable ‘psychological’ and physical symptoms of hypoglycemia.

14) High levels of insulin – hyperinsulinism – blocks the utilization of fat cells (adipocytes) as a source of energy, thus causing obesity. It also causes to dump magnesium into the urine, upsetting the delicate balance of intracellular magnesium and calcium ions that regulate blood pressure, thereby contributing to hypertension.

15) The brain requires an inordinate amount of biological energy (about 70-80% at any time), mainly derived from carbohydrates, to synthesize the feel-good neurotransmitters, such as serotonin. In the absence of energy the brain is energy starved, cannot synthesize neurotramsmitters and will trigger the release of stress hormones.

16) In hypoglycemia wild fluctuations in blood sugar levels causes the body to produce excess adrenaline, which functions to convert glycogen (stored sugar) into glucose in an attempt to stabilize the supply of glucose to the brain. The brain normally has no other source of energy than glucose and needs a stable supply.

17) Treatment of hypoglycemia is achieved by adopting a hypoglycemic diet accompanied with vitamin and mineral supplements (Vitamin C, Zinc, Chromium picolinate, Thiamine (B1) and other B-complex vitamins, see “The Hypoglycemic Diet” ). This helps to stabilize the blood sugar, insulin and stress hormone levels, even out mood swings, rebalance the appetite mechanism, equalize energy intake and expenditure; and halt if not reverse obesity.

18) The overproduction of adrenaline, known as the fight/flight hormone, can cause nervousness, panic attacks, anxiety, phobias, extreme mood swings and bouts of aggression and many other symptoms of hypoglycemia, described in the article “What is Hypoglycemia?” An immediate natural remedy (but not a cure) is Glycerine, that bypasses a faulty insulin production and directly enters glycolysis and may restore proper energy levels to the brain.

19) Depressant drugs, such as alcohol, tranquilizers, benzodiazepines, sleeping pills may temporarily counteract the effects of adrenaline, these are however very addictive and this helps to explain how hypoglycemia may lead to alcohol or drug addiction. Most drug addicts have been found to be hypoglycemic!

20) It is suggested that insulin resistance may also interfere with the absorption of other essential amino acids such as phenylalanine and tyrosine, which are forerunners of important brain neurotransmitters, such as dopamine and norepinephrine.

21) Norepinephrine (closely associated with dopamine) is believed to be a neurotransmitter that blocks out any irrelevant information from the brain and helps a person (usually young children) to concentrate on the task at hand. An error in norepinephrine synthesis has been associated with Attention Deficit and Hyperactivity Disorder (ADHD), because the person is bombarded with irrelevant information and cannot concentrate. Thus ADHD is considered another consequence of insulin resistance and hypoglycemia.

22) Hypoglycemia and/or insulin resistance is believed to result in a dysfunction of dopamine metabolism. Dopamine conveys the sensation of pleasure and many addictive drugs such as heroin and cocaine increase the amount of dopamine, by blocking (inhibiting) the reabsorption (reuptake) of dopamine by brain cells. This causes increased levels of dopamine which is felt by the addict as a high and as a feeling of great pleasure.

23) The presence of excess dopamine in the brain causes the down-regulation of dopamine receptors as a defence against superfluous dopamine. Receptors for dopamine are reduced and the person becomes dependent on the heroin, cocaine or any other addictive drug to artificially obtain ‘normal’ levels of dopamine. Treatment aims at rebuilding natural dopamine receptors through abstinence from drugs and with nutritional aids, such as omega-3 essential fatty acids (fish oil) which is thought to help restore brain cell membranes.

24) Treatment aims at reversing the Serotonin Connection by correcting the chemical imbalance of the various neurotransmitters. It is essential that the patient adopt the hypoglycemic diet together with nutrient supplements, vitamins and minerals, omega-3 fatty acids, neurotransmitter precursors, exercises and so on as explained in the article Treatment of Drug Addiction. This is generally a medical treatment intended to restore a person’s health.

25) Considering exposure to emotional STRESS as being a possible factor of the Serotonin Connection, it is important that the person undergoes a course of  psychotherapy to help him deal with stress situations more effectively by learning new social skills. But it is important to realize that psychotherapy can only be effective AFTER treatment of the biochmical factors. Talk therapy can not “cure” a physiological abnormality. Such a course is available free of charge at the web Hypoglycemic site at: Psychotherapy Course.

Further readings:
“What is Hypoglycemia?”

“The Hypoglycemic Diet”

“Depression – a Nutritional Disorder”

“Depression – a Disease of Energy Production”

“Post Traumatic Stress Disorder (PTSD) and Hypoglycemia”

“Hypochondria and Hypoglycemia”

“Hit or Miss Supplements for Depression”

“Beating Anxiety and Panic Attacks”

52 Responses

  1. Xuxakat says:

    That is great material for a research I am doing right now. Thanks a lot!
    Could you answer me a question? Have you found studies that show that a serotonin deficiency can lead to an excess of cortisol? I always only found it the opposite way. I know that serotonin deficiency can lead to insulin-related issues that can lead to elevated cortisol levels. But if there were no such problems with insulin, could then a serotonin deficiency still cause an increase in cortisol? It sounds logical to me as taht condition might activate the HPA axis what could lead to an increase of cortisol, but I haven’t found any research on that topic. I even found a study saying that tryptophan depletion leads to lower morning cortisol.

  2. Jurriaan Plesman says:

    This is an interesting question. Whenever there is a serotonin deficiency it is indication that the body has problems producing serotonin from nutritional forerunners such as tryptophan. Environmental stress can interfere with serotonin synthesis. (Strickland) Tryptophan may be deficient because of niacin deficiency,in which case tryptophan is converted to niacin at the rate of 60 to 1. This may cause a tryptophan defiency. It may also be due to deficiencies of any of many the co-enzymes necessary in serotonin synthesis. (See 6) above.
    But it can also be caused by deficiency or biological energy called Adenosinetriphosphate (ATP) ultimately derived mainly from glucose metabolism.
    Thus when a person has problems converting carbohydrates into ATP as in hypoglycemia, causing dangerous brain starvation, it will trigger the release of stress hormones – adrenaline and cortisol. These hormones function to convert energy sources in the body – into glucose in order to feed the brain again. The brain cannot survive without glucose as its only source of energy.
    Hence stress hormones serve to feed the brain with energy in case of emegency. The brain is very sensitive to blood glucose levels.
    “The name glucocorticoid (glucose + cortex + steroid) derives from their role in the regulation of the metabolism of amino acids into glucose. Wikipedia
    Adrenaline is a hormone that triggers the conversion of glycogen into glucose.
    Thus yes, there is an association between serotonin deficiency and production of stress hormones whenever the brain senses energy starvation as in hypoglycemia.

    There are of course other silent diseases (look up) that can cause brain starvation resulting in stress hormones production.
    I hope this answers the question.
    Jurriaan Plesman

  3. Jasmine says:

    This is a life saving site! I’m so glad to finally find information about my condition which really ruined my life for the past 8 years. I always beleived that my depression was caused by hypoglycemia but NO ONE doctor agreed with me. I was diagnosed with agoraphobia and that due to having low blood sugar attacks while i was at university, and having these attacks led to fear and anxiety not knowing what’s wrong with me until i went through a severe depression, anxiety and panic attacks. Now i’m on seroxat 30 mg per day for the past 8 years and i admit that i’m an addict now and it’s horrible as it’s hard to quit the med due to its severe withdrawal symptoms and I really want to quit the med but don’t know from where to start how, when and what to do! i really need help! i’m going to follow the hypoglycemic diet with therapy and accupunture in a hope of getting my life back.

    Again thanks for these wonderul information

    People out there who read this and are facing the same problems please feel free to contact me on the below email maybe we can support each other. bassilko@gmail.com
    Best regards,

  4. Jurriaan Plesman says:

    Hi Jasmine,
    I know how you must feel. 
    I too suffered for many years from mood disorder without understanding why. But there is indeed hope. When you feel you are addicted to psychotropic drugs, never withdraw “cold turkey’. 
    The idea behind nutritional therapy is to first treat the underlying nutritional disorder before anything else. 

    There are plenty of studies showing that HYPOGLYCEMIA is a major if not the most important factor in depression. (See RESEARCH EVIDENCE FOR HYPOGLYCEMIA)


    When you start to feel better whilst you are on the HYPOGLYCEMIC DIET, you should begin to think about WITHDRAWING from drugs very gradually and preferably under doctor’s supervision. 
    Also research GLYCERINE to help you beat anxiety and possibly insomnia. 
    The quickest way is of course to work with a nutritional doctor or therapist.
    The principle in nutritional therapy is to FIRST treat the underlying metabolic disorder, before withdrawing.
    When you feel you are not feeling better on the Hypo diet, we need to look at other factors, such hypothyroidism, allergies etc 

    The more you know about nutritional therapy, the less time you waste consulting nutritional therapists or doctors. 

  5. Nathan Becker says:

    Why do you say never to quit psychotropic drugs cold turkey? I was taking Ambien as directed for 6 weeks and decided to quit cold turkey after experiencing inter-dose withdrawal. Within a day, I started having massive panic and anxiety attacks, depression, and total systemic malaise. The intense symptoms abated over the next few days, but a general sense of unease and anxiety and depression plagued me throughout the week after withdrawing, and I slept perhaps an hour or so per night. Now, 8 days free of Ambien, I feel like I’m stabilizing to some degree.

    Is your suggestion not to quit cold turkey simply based on the fact that cold turkey intensifies withdrawal symptoms, or is there some evidence to show that cold turkeying can perhaps do some permanent damage?

  6. Jurriaan Plesman says:

    Withdrawing from psychotropic drugs “cold turkey” can be dangerous. 


    “The symptoms of too-rapid withdrawal from psychiatric drugs include extreme nausea, anxiety, insomnia, restlessness, muscular reactions, and strange behaviour. In the case of minor tranquilizers and sedatives, the reactions to sudden withdrawal can be life-threatening.”


  7. Nathan Becker says:

    Oh, certainly, the acute effects of cold turkey withdrawal are dangerous, and in many ways. I’m now 9 days removed from Ambien, and I feel so much better at this point, but the first full week was an absolute war with my body and mind. Never have I experienced anything so terrifying, intense, and systemic. Right now, I have a low-grade and intermittent anxiety issue which I assume is still a function of my withdrawal as I have never had any real anxiety or stress issues before in my life.

    What I’m interested in is whether or not such an intense, acute shock to my central nervous system will have lasting (e.g. permanent) effects, and if there is any research evidence to support any related claims. I ask because I haven’t been able to find any such articles myself, but perhaps you are aware of some existing information on the long-term effects of acute/cold-turkey withdrawal?

  8. Jurriaan Plesman says:

    Whatever the psychological symptoms are, they usually cannot be cured by drugs, although they may mask symptoms. This is why in nutritional psychotherapy you FIRST treat the underlying metabolic disorder possibly responsible for mood disorder BEFORE withdrawing from drugs (under doctor’s supervision). 
    I suggest that you adopt the hypoglycemic diet and use GLYCERINE (look up) to lessen ongoing feelings of anxiety. 
    If things don’t improve within the next three weeks, please consult a Nutritional Doctor. I hope I have been of some help. 

  9. susan bevis says:

    I would like to purchase your article to pass on to the team where my daughter currently is. She has been on about 14/15 different drugs and none have worked. The shocking care at the Bethlem Royal Hospital where she was referred for a drug free period of assessment led to her being plied with Olanzapine mixed with Seroquel which caused her to go psychotic – she was already suffering from Akathisia on Seroquel 750mg. Now they have put her on Metformne and Clozapine and I am horrified by this. She has been transferred miles from home to a private hospital called Cambian 4 Star Wards. Anyway I would like to buy your article to show to the team there – already the psychiatrist does not like me and the law has changed in Wales allowing hollistic care and I want this for my daughter who should never have been put on these chemicals in the first place as she was a victim of crime. Now I want her off them or else on t he minimal of these drugs. I would like to buy something from you to show to the team and so please can you send me a bill that I can pay through paypal or something like this via my email address above. The hospital did wrong taking her off such a large dosage and as thre is a tribunal coming up I need something to show the team from experts that this simply is the cause of psychosis to come off a large amount. It is disgusting what is going on in the UK and I would like some change and already things are changing in Ireland where patients have the right to say No or so I believe and in Wales a patient can choose hollistic care and the law has just changed. I look forward to hearing from you. Also I would like you to come up with a diet that my daughter should be having. She has aspergers and schizophrenina mentioned in the files and I do not believe the diagnoses as nothing has been done properly and professor murray said a drug free period and he has let us all down tremendously. They are the ones to cause the psychosis at the Maudsley hospital – no wonder it is called the National Psychosis Unit and you should see the horrifying sights on this ward. I was banned completely and given and not even allowed to visit my daughter and they could give me no reasons for this behaviour. I brought wonderful things onto their ward from Dr Tracy and I am always looking to learn more in the way of alternative care as this is the answer as everything else has failed for my daughter.

    I look forward to hearing from you and will need this information urgently as there is a tribunal coming up on the 12th September.


    Susan Bevis

    • Jurriaan Plesman says:

      Hello Susan,
      We are strictly a non-profit organization and all articles published at our web site are freely available for anybody to read. All you need to do is to acknowledge the source. We understand how difficult it is for patients and carers to encourage doctor to even consider complementary medicine. My advise is to get hold of a nutritional doctor and see if they can be of any help to doctors in the hospital. In cases of psychotic disorders it is not always possible to treat them with complementary medicine alone. Usually, it is combination of drug and nutritional therapy. The hospital needs to be geared at being able to carry out nutritional tests to obtain an accurate diagnosis. I also suggest to research:
      Alternative Mental Health articles:

  10. Sheree DuBois says:

    I am angry!
    I am 49 yrs old, have had a traumatic childhood (stress) and have been medicated for depresion for years. I have done a LOT of psychology treatment, read every self help book I could lay my hands on! Because of this I have now been unmedicated for 2 yrs.
    In my 20s I was diagnosed by Professor Heller (Carbohydrate Addicts Diet) as hypogycemic. I hav gradually put on weight. The Drs had blamed this on antidepressant meds and I believed them, but since Ive been unmedicated i havent been ablle to lose the weight.
    I have had prolonged stress
    I have had depression, with bipolar tenancies (Cyclothymia)
    I have had terrible PMT
    I have high blood pressure
    I have polycystic ovaries
    I have been diagnosed as hypogycemic
    so…. 29 yrs later I am insulin resistant and prediabetic!!
    I have found this out by doing research myself then going to the Drs…a month ago I went 3 days in a row because Im sick of asking the same questions for nearly 30 yrs without proper answers or treatment.
    I am now taking chromium and vanadium along with multi vits, fish oil and Bvits.
    I have begun a “diabetic” diet and for the first time since I can remember I dont crave sugar!
    Im so upset that Ive had no help with all this…just put me on Prozac!!!
    thanks for reading

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