Fibromyalgia and Serotonin

Serotonin is important for initiating sleep and adapting to stressful situations. It also gives us an ability to cope with depression. However, sometimes serotonin does just the opposite to us. It causes insomnia and/or depression. This seems to be the case in fibromyalgia. A mishandling of serotonin plays a part in creating the insomnia, fatigue, fibro-fog, pain and depression of fibromyalgia.

Some of the earlier investigations into fibromyalgia indicated that the blood’s serum levels of serotonin might be low. More recently, a study using a different method of investigation showed that most people with fibromyalgia have very high levels of serotonin present in the blood’s plasma rich platelets, although there were also a few people who had very little serotonin. [2] So which is it? Too much or too little? Or is the most important thing how the serotonin is being used?

The real problem is the misuse of serotonin. In many ways, the body of someone with fibromyalgia acts like it has too much serotonin. There are many observations that are very consistent with an excessive serotonin-like influence.

1. Central Hypothyroidism. Chronic pain or stress elevates free serotonin in the brain and this induces central hypothyroidism. [3] (Hypothyroidism means the body doesn’t have enough thyroid hormone. This causes fatigue, mood alterations, and poor immunity. “Central” hypothyroidism means that the brain isn’t telling the thyroid gland to create and release thyroid hormone.) Central hypothyroidism occurs in about half the people who have fibromyalgia. This suggests that free serotonin might be too high in parts of the brain.

2. Hormone Dysregulation. Serotonin promotes the formation of corticotropin-releasing hormone (CRH). An activation of the CRH neurons would disturb regulation of many hormones in exactly the same manner as observed in fibromyalgia. [3] (Other types of stressors, such as infection and pain also increase CRH.)

3. Disrupted Non-REM Sleep. Serotonin promotes the formation of CRH, and CRH increases spontaneous waking and reduces Non-REM sleep. [4] Those with fibromyalgia experience poor Non-REM sleep. (REM means rapid-eye-movement.) In fact, just a lack of non-REM stage 4 sleep may cause muscle pain and mood changes similar to fibromyalgia.

4. Elevated Substance P. Substance P is elevated in the spinal fluid of those with fibromyalgia. This heightens the sensitivity to pain. Since serotonin increases substance P, this is another indication that perhaps free serotonin is elevated.

5. Defective Mitochondria. In fibromyalgia, defects in the cells’ mitochondria have been observed. When cells are exposed to free serotonin, it poisons the cells’ mitochondria. [5] This disrupts energy production and causes fatigue. (“Free” serotonin means that the serotonin is not contained within cells. It is surrounding the cells. When cells are left to soak in a bath of serotonin, it damages their mitochondria.)

6. Elevated cytokine IL-6. An immune system cytokine called IL-6 is elevated in fibromyalgia. IL-6 decreases REM sleep, causes fatigue, and interferes with concentration in humans. [6, 7] Free serotonin and substance P both may increase this IL-6 cytokine. [6, 8 ] This is yet another hint that free serotonin might be high.

7. Blood Coagulation and Fibrin. Increased blood clotting and fibrin formation has been observed in fibromyalgia. Free serotonin promotes this.

8. Poor Microcirculation. This interferes with oxygen getting to the cells. Free serotonin contributes to poor microcirculation by increasing fibrin formation and constricting blood flow. (When you are cut, some of the cells release serotonin. This constricts blood vessels and helps form a clot. This is an important function because the bleeding from a cut needs to be stopped. The released serotonin helps the body do this. However, you don’t want serotonin to be released when it isn’t needed. This would be a harmful misuse of serotonin.)

All of the above is consistent with a high presence of free serotonin in parts of the brain and possibly elsewhere in the body.

Serotonin Dominance?

Why could there be such a strong serotonin-like influence in fibromyalgia? Here are a few possibilities.

1. Early life stress. There is an enzyme in the brain that converts tryptophan into serotonin. This enzyme can be activated under prenatal or early life stress and not return to normal activity levels. [1] Activation of this enzyme means that there would be more serotonin in the brain. eg. Blood serotonin levels could look normal or even low, although the brain has plenty of serotonin.

2. Excess ammonia. Ammonia increases the amount of tryptophan entering the brain. Subsequently, this increases the amount of serotonin in the brain and enhances its use. [9]

3. Whiplash. This could set the stage for an infection in the brain stem. The infection would cause an immune response, and the cytokines from this immune response would create a strong serotonin-like influence in the brain’s hypothalamus. (The hypothalamus regulates hormones, and affects the autonomic nervous system.)

4. Poor intestinal flora. Lipopolysaccharide (LPS) is a toxin found in the shell of gramnegative bacteria. This toxin makes a person feel sick. It also increases the release of serotonin in the brain’s hypothalamus and changes the way the body regulates hormones. [3, 10]

5. The leaking of serotonin from cells. There is some preliminary indication that serotonin is leaking out of cells in fibromyalgia. The cells appear to be releasing their serotonin into the blood’s plasma compartments. Testing showed that higher plasma to serum ratios of serotonin meant higher pain and anxiety. [11] In other words, the more the cells leak serotonin, the more pain and anxiety that is present. When serotonin is outside of cells, it can be very harmful.

Is Serotonin Leaking from Cells?

If the cells are leaking serotonin, what could be causing this? Are pesticides and chemicals to blame? Stress? Bacterial toxins? Here are some possible scenarios:

1. Lipopolysaccharide (LPS). This is a toxin that is found in the shell of gram-negative intestinal bacteria. LPS can release serotonin from mast cells. LPS can also increase platelet aggregation and this leads to increased release of serotonin from the platelets. [12] Hence LPS can increase free serotonin levels.

2. Intestinal Inflammation. This causes the intestinal enterochromaffin cells to dump serotonin. Some of this ends up in the general circulation.

3. Low Magnesium. This increases the likelihood that platelets and mast cells will release their serotonin and histamine.

4. Stress Plus Polyunsaturated Oils. Stress, combined with excess polyunsaturated oils in the diet, will cause serotonin to leak from cells.

This is Dr. Raymond Peat’s explanation of the relationship between stress, fats, and serotonin leaking from cells:

Stress also liberates free fatty acids from storage, and these fatty acids increase the uptake of tryptophan into the brain, increasing the formation of serotonin. … Serotonin liberates polyunsaturated fats, and these in turn liberate serotonin from cells such as the platelets, and liberates tryptophan from serum albumin, increasing its uptake and the formation of serotonin in the brain. Saturated fats don’t liberate serotonin …[5]

Therefore, it seems prudent to eliminate most of the polyunsaturated oils in the diet Corn, safflower, cottonseed, canola, soy, fish, flax and most oils from nuts are all high in polyunsaturated fatty acids. Notice that fish and flax oils are in this list of polyunsaturated oils. Even though there is some benefit to limited use of fish and flax oils, too much can be quite harmful. In my opinion, one should limit their fats/oils to mainly butter, olive and coconut.

Natural factors that will help keep serotonin levels under control are thyroid, protein, magnesium, carbon dioxide, decreased tryptophan consumption, vitamin B1, progesterone and exposure to light. [5, 13] Also, the amino acid glycine may counter some of the effects of excess serotonin. Compare this list of harmful effects of excess serotonin with this list of protective properties of glycine. Raymond Peat, PhD states:

“Serotonin excess produces a broad range of harmful effects: Cancer, inflammation, fibrosis, neurological damage, shock, broncho-constriction, and hypertension, for example. Increased serotonin impairs learning, serotonin antagonists improve it. The simplest, nonessential, amino acid, glycine, has been found to protect against carcinogenesis, inflammation, fibrosis, neurological damage, shock, asthma, and hypertension. Increased glycine improves learning (Handlemann, et al., 1989; File, et al., 1999), glycine antagonists usually impair it.” [5]

Although the benefits of a glycine supplement are impressive, please be careful. Oral glycine can feed some bacteria in preference to others. This shift in population may or may not be good. If you wish to purchase some glycine, a bottle of just glycine powder will be cheaper than encapsulated glycine. Glycine tastes sweet, so you probably won’t mind the taste of it.

To stop the leaking of serotonin, a person needs to increase magnesium, eliminate food allergies, eliminate stress, eliminate much of the gram-negative bacteria in the intestines, and eliminate most of the polyunsaturated oils from the diet.

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