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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. James says:

    What if any research have you done on useing a vitamin/magnesium supplement to deal with depression and anxiety?

    • Jurriaan Plesman says:

      The production of serotonin – the feel-good neurotransmitter – requires a multitude of enzymes, co-enzymes and nutrients to complete transformation into serotonin. Furthermore, each individual has a unique biochemistry – “one man’s meat is another man’s toxin”. Lacking any one of the necessary factors can stop the production of serotonin. Therefore, the best strategy is to aim at a diet that is the most natural and inclusive. For instance the paleolithic diet. For people with hypoglycemia the best diet is the hypoglycemic diet.
      Hit or Miss Supplements for Depression

  2. Joe P says:

    5-HTP is probably the best supplement for someone who is serotonin deficient. It the direct precursor to serotonin, whereas tryptophan is the direct precursor to 5-HTP.

    Also supplement with vitamin B6 as it is required in the conversion of tryptophan to serotonin.

    Probably the best remedy is proper diet, exercise and removing stress, however sometimes we need some help getting to a point where we can change our life or our diet.

  3. ron says:

    I’m interested in your take on how a mild cortisol deficiency might also lead to low serotonin-levels? In my own case, years ago I had a whopping case of “chronic-fatigue syndrome” which was resolved with cortisol meds. During my years of sickness, I experienced, among other things, a permanently switched-on fight/flight response, and no sleep or drowsiness at all, literally for years. Never fully awake, either, in a constant brain-fog. Could it be that the non-reactive hypoglycemia I also had from low cortisol caused my low-energy brain to not be able to make serotonin, causing the cycle of insomnia which leads to more cortisol deficiency as cortisol is mostly produced during deep sleep?

    • Jurriaan Plesman says:

      I believe that Chronic Fatigue Syndrome is caused by lack of biological energy due to hypoglycemia. Hypoglycemia can trigger the release of adrenaline and cortisol in an endeavor to rebalance energy levels to the brain. These hormones emanate from the adrenal glands and may eventually exhaust that gland causing adrenal exhaustion, leading to chronic fatigue. Adrenaline and cortisol are not the source of energy, but hormones to release stored energy in the body. Ultimately that energy has to come from our diet and since I consider the hypoglycemic diet to be the natural hunter-gatherer’s diet, it is the proper diet adapted to the individual that can restore normal energy sources to the body.

    • silvan says:

      Hey Ron I can’t sleep either and I’m pretty much a zombie my sleep problem sounds almost like yours.For the last 3years or so I stopped sleeping and became irritated and paranoid and couldn’t figure it out for nothing.Well I got my cortisol levels tested and they came back low at 31 8.5% plus low progesterone and Low T,did you have numbers similar to this.Any way I’m trying to get to a Endo now my test rsults came from a holistic multi care practioner and I don’t think they specialize in adrenal or low cortisol.Well alright I hope to hear back from you soon this sleep disorder has been a nightmare only if I could sleep I could have dreams.

  4. Ron says:

    Hi and thanks,
    Yes, seems hypoglycemia has been underrated as far as the chronic-fatigue community goes. From my own experience and also subsequent research, without enough cortisol in the body (or abnormal receptors), blood-sugar levels are never up to par–in my case the fasting levels were always in the low 50’s or high 40’s. And as endocrinologist Jefferies used to say, the main causes of non-reactive hypo. were either low thyroid or low cortisol. Low blood-sugar triggers adrenaline-release, and along with low serotonin, now we don’t sleep, so don’t produce enough cortisol, and the cycle continues. I’ve yet to see one CFS-expert mention this!

  5. Jurriaan Plesman says:

    I know it is very difficult for conventional doctors to accept and understand what prediabetic insulin resistance is. I suggest that you contact nutritional doctors in future.

  6. Serotonin says:

    Serotonin is the most fascinating neurotransmitter I know, by the time passes a lot of new things are discovered about it.

    I saw in the article that you said how can serotonin can be produced through ingestion of food, in some way. I will also like to add that serotonin levels can be raised through Sunlight at sepecific times, massages, positive thinking and physical exercises.

  7. silvan says:

    Hello Ron My email is sylvan365@yahoo.com If you could email me your post sleep condition and cortisol problems if they were fixed quickly or did it take a while to get back to normal.Thanks…Silvan

  8. John Ripi says:

    I have a high level of serotonin 1382. Is there any natural substance, vitamin, mineral or what ever that can lower it. Too high a serotonin level
    does contribute to heart valve disease. Please, this is serious. I have Carcinoid tumors that produce the serotonin. I’d appreciate any helpful
    suggestion. Thank you.

    John R.

  9. fred says:


    may i get your opinion on treatment of OCD and diet for OCD?

    thank you in advance.

  10. Diana says:

    My 48 yr old son has successfully been on medication for nine years to treat anxiety/depression caused by an adrenaline/serotonin imbalance. Four months ago his doctor decided to reduce the dosage and a short time later his symptoms returned. He was put back on the full dosage but more than six weeks later there is no improvement. He has lost weight, is sleeping badly and shakes constantly. What other treatment can he have?

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