The complete cause of the metabolic syndrome is not known at the present time. The metabolic syndrome is demonstrated by abdominal obesity, altered glucose metabolism, abnormal lipid metabolism and high blood pressure.

The metabolic syndrome has been defined by the National Cholesterol Education Program (NCEP) as at least three of the following:

1. Fasting blood glucose of 110 mg/dl or higher.

2. Serum triglyceride of 150 mg/dl or higher.

3. HDL cholesterol less than 40 mg/dl in men.

HDL cholesterol less than 50 mg/dl in women.

4. Blood pressure of 130/85 or higher.

5. Waist circumference over 102 cm. in men or over 88 cm. in women.

The International Diabetes Federation (IDF) defines the metabolic syndrome as being central obesity (waist circumference at least 94 cm. in men or 88 cm. in women) and at least two of the following:

1. Fasting blood triglyceride of 150 mg/dl or higher.

2. HDL cholesterol less than 40 mg/dl in men or less than 50 mg/dl in women.

3. Blood pressure of 130/85 mm Hg or higher.

4. Fasting glucose of 100 mg/dl or higher.

The goal behind the present study is to see if the metabolic syndrome is related to low serotonin neurotransmitter response in the brain. This is based on the idea that metabolism and blood pressure abnormalities are typical of the metabolic syndrome and they are both partly controlled by serotonin in the brain, which produced primarily in the brain stem.

To test the brain’s connection with the metabolic syndrome patients were given an intravenous dose of a medicine (citalopram) that should cause increased serotonin in the brain. The patients are then tested for the production of prolactin, which is a test for serotonin activity in the hypothalamic-pituitary axis in the brain. Increased serotonin production stimulated by the citalopram should result in increased prolactin. (Citalopram is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin in the brain).

Body size measurements, blood pressure and blood samples were tested for 328 patients. The results of the testing of patients who met the criteria for metabolic syndrome were compared with those who did not. The result was that those who were found to have metabolic syndrome had a reduced prolactin response compared to those who did not have metabolic syndrome. A reduced serotonin response is implied by these results.

CONCLUSION: The metabolic syndrome has been found to be associated with reduced brain serotonin activity. This is indicated by a reduced prolactin response to a serotonin stimulator (intravenous citalopram). In people who met the definition of metabolic syndrome the low prolactin response correlated with increased insulin resistance. “This association may have implications for the etiology, prevention and treatment of the metabolic syndrome.” Further testing needs to be done to see if the reduced serotonin production precedes the metabolic syndrome.

NOTE: Insulin resistance has been seen in some studies as the result of antibodies against insulin. Summary 147 discusses that the metabolic syndrome is promoted by the glucocorticoids produced by the adrenals as a result of stress. Summary 127 discusses the part dietary fructose plays in the metabolic syndrome by increasing uric acid. There is evidence that lowering the uric acid reduces metabolic syndrome. There are supplements that help reduce serum uric acid levels listed in Summary 127.

This article does not evaluate the benefit from the use of supplements to increase serotonin levels in treating metabolic syndrome and studies need to be done. Tryptophan and 5-OH tryptophan have been shown to be converted to serotonin in the body.

PMID: 16303834.

Summary #151.