Serotonin by Ray Sahelian, M.D. Is there a serotonin supplement?

How to Increase Serotonin, Naturally
5-HTP supplement for sale -- a natural serotonin precursor
Plus: Mind Power Rx for healthy brain and mood support
Plus: Good Night Rx, natural herbal sleep aid

Subscribe to a FREE Supplement Research Update newsletter. Twice a month we email a brief abstract of several studies on various supplements and natural medicine topics, including serotonin research, and their practical interpretation by Ray Sahelian, M.D., author of Mind Boosters. This link leads to an index of more than 300 natural medicine topics

Serotonin happens to be the most widely studied neurotransmitter since it helps regulate a vast range of psychological and biological functions. Serotonin (5-hydroxytryptamine or 5-HT) was first identified in 1948. The wide extent of psychological functions regulated by serotonin involves mood, anxiety, arousal, aggression, impulse control, and thinking abilities. Other brain chemicals, such as dopamine and norepinephrine, also influence mood and arousal. However, serotonin generally has different effects. For instance, excess amounts of serotonin cause relaxation, sedation, and a decrease in sexual drive. Serotonin deficiency is associated with low mood, lack of will power, and poor appetite control.
     Disruption of the normal functioning of the serotonin system leads to a number of psychiatric conditions, which include anxiety disorders, depression, improper social behavior, and sexual aberrations. Common medical conditions associated with disruption of the serotonin system include disturbance in the sleep-wake cycle, obesity or eating disorders, and chronic pain.

Formation of Serotonin
The figure below shows tryptophan converting into 5-HTP, which then readily converts into serotonin. Once serotonin is made, the pineal gland is able to convert it at night into melatonin, the sleep-inducing hormone. Vitamin B6 is involved in the process of serotonin formation.

Tryptophan, 5-HTP, and melatonin are available for sale as supplements.
Serotonin is not sold since it cannot easily cross the blood brain barrier while tryptophan, 5-HTP and melatonin easily cross from the blood stream into the brain. 5-HTP is a natural serotonin precursor.

Tryptophan*
(available for sale, click the link)

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5-Hydroxy-Tryptophan (5-HTP)
(available for sale, see below)
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Serotonin
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N- Acetyl Serotonin
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Melatonin

*Note: Tryptophan is also metabolized on a different pathway, not all of it is converted into 5-HTP.

Figure 13.2 from the book Mind Boosters: Natural Supplements that enhance mind, memory, and mood: Conversion of Tryptophan into 5-HTP, Serotonin and Melatonin
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5-HTP 50 mg Natural Serotonin Precursor - 5-HTP converts into Serotonin
Formulated by Ray Sahelian, M.D.


HPLC tested - Purity and potency guaranteed by Dr. Sahelian. For low serotonin.

Amount Per Capsule:
5-HTP -  50 mg
Vitamin C - 10 mg
Vitamin E - 10 iu

Vitamin C and Vitamin E added as antioxidants

Click here to buy 5-HTP, Mind Power Rx, or to sign up to a highly popular and respected FREE newsletter
Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive a review of several studies on supplements and natural medicine topics, including serotonin, and their practical interpretation by Ray Sahelian, M.D. We will discuss serotonin, tryptophan, and 5-HTP.

Mind Power Rx - Formulated by Ray Sahelian, M.D. -- Supports Serotonin, Dopamine, Acetylchoine, and several other neurotransmitters.

Mind Power Rx is a sophisticated cognitive formula. It combines a delicate balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support:

• Memory and Mood
• Mental clarity
• Concentration 
• Alertness & Focus

The herbs in Mind Power Rx include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba,  Ginseng, Gotu kola, Mucuna pruriens, Reishi, and Rhodiola.  The nutrients and vitamins in Mind Power Rx include Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Pantothenic acid, Trimethylglycine, Tyrosine, and Vinpocetine.
Click 5-htp above in blue for more information
 

Good Night Rx helps you sleep deeper

Developed by Ray Sahelian, M.D.

 

Good Night Rx Supplement Facts:
Serving size: One Capsule
Servings per container: 60

Suggested Use: Take one capsule of Good Night Rx one to three hours before sleep, preferably on an empty stomach. Good Night Rx does not work as well when taken with a meal. Good Night Rx is formulated for those who need natural help due to occasional sleeplessness.

Click 5-htp above in blue for more information

Serotonin reuptake inhibitor
Several drugs are sold as serotonin reuptake inhibitors, such as Prozac, Paxil, Zoloft and others. These serotonin drugs are used for depression with some success. Side effects of selective serotonin reuptake inhibitors include loss of sex drive, headache, nausea, and sleep disturbances.

Natural ways to influence Serotonin levels
There is an over-the-counter nutrient called 5-hydroxytryptophan (
5-HTP) that is the immediate precursor to serotonin and can, in some cases, temporarily substitute for serotonin-influencing drugs. 5-HTP may play a role in reducing anxiety and depression. Tryptophan is another option since it converts into 5-HTP. Some research suggests that perhaps the herbal antidepressant St. John’s wort also works by influencing levels of serotonin in the brain.

Side effects of Serotonin - Caution with Serotonin Syndrome
One of the side effects of excess serotonin is reduced sex drive, which occurs with the use of selective serotonin reuptake inhibitors. Fortunately, there are many natural sex herbs that can reverse this process and boost libido, erectile function, and enhance orgasms and climaxes.
   A serious concern with excess serotonin that can sometimes occur from the misuse of a
selective serotonin reuptake inhibitor is serotonin syndrome. Excessive stimulation of serotonin receptors is usually a result of administration of a high dose serotonin agonist to a patient who is already receiving a drug capable of potentiating the serotonin pathways. This could occur as a result of decreased serotonin re-uptake (from tricyclic antidepressants), decreased serotonin metabolism (from monoamine oxidase inhibitors), or excessive adminstration of serotonin precursors or agonists (trazodone, L-tryptophan, 5-HTP).Certain street drugs may cause serotonin syndrome. These include cocaine and MDMA or "ecstacy." Caution is advised when combining drugs or supplements that have an effect on the serotonin system.
   A serious serotonin syndrome symptom is coma. Other symptoms include confusion and agitation.
 
Serotonin Syndrome with SSRI and Lithium
Serotonin syndrome, which occurs as a result of enhanced serotonin concentration in the central nervous system, is a well-known adverse effect of serotonin-active medications. The use of SSRi drugs along with lithium increases the risk of serotonin syndrome.
   
Serotonin and Premature Ejaculation
Increasing serotonin levels with SSRIs or 5-HTP can be helpful to those with premature ejaculation.

Serotonin Reuptake Inhibitors
Prozac, Paxil, Zoloft, and other selective serotonin reuptake inhibitors elevate serotonin levels in the brain, and perhaps influence the levels of other brain chemicals such as norepinephrine.

Serotonin Research Update
Effect of orally administered L-tryptophan on serotonin, melatonin, and the innate immune response in the rat.
Mol Cell Biochem. 2004 Dec;267(1-2):39-46.
To assess the effects of external administration of L- tryptophan on the synthesis of serotonin and melatonin as well as on the immune function of Wistar rats, 300 mg of the amino acid were administered either during daylight (08:00) or at night (20:00) for 5 days. Brain, plasma, and peritoneal macrophage samples were collected 4 h after the administration. The accumulation of 5-hydroxytryptophan ( 5HTP ) after decarboxylase inhibition was used to measure the rate of tryptophan hydroxylation in vivo. The results showed a diurnal increase in the brain 5HTP, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindolacetic acid (5-HIAA) of the animals which had received tryptophan at 08:00 and were killed 4 h later. In the animals which received tryptophan during the dark period, the serotonin declined but the serotonin /5-HIAA ratio remained unchanged. There was also a significant increase in nocturnal circulating melatonin levels. The results indicated that the synthesis of serotonin and melatonin, as well as the innate immune response, can be modulated by oral ingestion of tryptophan.

Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain.
Arch Med Res. 2004 Jul-Aug;35(4):271-4.
The aim of this study was to evaluate effects of pyridoxine and butylated hydroxytoluene (BHT) on lipid peroxidation and on levels of 5-hydroxytryptophan and serotonin. Thirty rats were used in the survey, measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxytryptophan (5-HTP), and serotonin after intraperitoneal injections of pyridoxine HCl during 20 days and a single dose of BHT. RESULTS: Levels of TBARS and 5-HTP increased considerably in all vitamin- and/or BHT-treated groups, and serotonin increased partially only in B(6) with or without BHT-treated groups compared with control group. CONCLUSIONS: Results suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-HTP.

Corticosteroids, depression and the role of serotonin.

Pretorius E.University of Pretoria, South Africa.
Patients frequently use medications simultaneously for different complaints, without being aware of the interactions these products may have. An example of this is the simultaneous use of corticosteroids and medications for depression, defiant or aggressive behavior. Research has also indicated that corticosteroids lower serotonin levels. However, lowered serotonin levels may result in depression, aggression and other psychological conditions. These secondary complaints, caused by the corticosteroids and other products that lower serotonin levels, may then be treated with selective serotonin reuptake inhibitors or psycho-stimulants (that are known to indirectly increase serotonin levels). The current research takes a look at lowered serotonin levels when using corticosteroids, as well as the interactions with serotonin reuptake inhibitors and psycho-stimulants. Furthermore, evidence is presented to prove the hypothesis that some individuals with asthma (e.g. children using systemic corticosteroids that lower serotonin levels) might present with symptoms of depression, attention deficit hyperactivity disorder, oppositional defiant disorder and even conduct disorder; and that treating these secondary complaints with serotonin reuptake inhibitors and psycho-stimulants will result in the upregulating of serotonin levels, and that, in turn, will trigger asthma.

Tryptophan administration increase contractility and change the ultrastructure of mice duodenum.
Amino Acids. 2004 Oct;27(2):215-20. Epub 2004 Jun 21.
Serotonin is a metabolite of tryptophan. Serotonin has been shown to induce contractions in rat duodenum and ileum. We planned to investigate the in vivo effects of Tryptophan administration on duodenal contractility and ultrastructure together. Two equal groups of adult male Swiss-albino mice were used in the experiments. Controls and Tryptophan treated (100 mg/kg/24 hr in 0.2 ml. saline solution ip, 7 days). Body weights decreased and duodenal contractile response of ACh increased significantly by Tryptophan treatment. The duodenal ultrastructural changes in Tryptophan group illustrated partially loss of apical surface and fusion in microvilli. Immunohistochemical detection showed that Serotonin increased by Tryptophan treatment. There is a relation between duodenal contractility increased by Tryptophan treatment and changes in the duodenal tissue Serotonin level and ultrastructure.

Protective effect of N-acetyl- serotonin on the nonenzymatic lipid peroxidation in rat testicular microsomes and mitochondria.
J Pineal Res. 2004 Oct;37(3):153-60.
N-acetyl- serotonin, the immediate precursor of melatonin in the tryptophan metabolic pathway in the pineal gland, has been reported to be an antioxidant. The aim of this study was to test the in vitro protective effect of N-acetyl- serotonin on the ascorbate-Fe(++) induced lipid peroxidation of polyunsaturated fatty acids (PUFAs) located in testis microsomes and mitochondria. We assayed increasing concentrations (0-10 mm) of N-acetyl- serotonin in testis microsomes and (0-1 mm) of N-acetyl- serotonin in testis mitochondria. Control experiments were performed by incubating microsomal and mitochondrial membranes with N-acetyl- serotonin in the absence of lipid peroxidation-inducing drugs.  N-acetyl- serotonin reduced lipid peroxidation in testicular microsomes or mitochondria for both C20:4 n6 and C22:5 n6. Both long chain PUFAs were protected when N-acetyl- serotonin was incorporated either into microsomes or mitochondria. In these experimental conditions, N-acetyl- serotonin was about 18 times more potent in testicular mitochondria in inhibiting the oxidative processes than it was in testicular microsomes. These results suggest that the protective role of N-acetyl- serotonin in preserving the long PUFAs may be related to its ability to reduce lipid peroxidation.

Serotonin in autism and pediatric epilepsies.
Chugani DC. Detroit Medical Center, Wayne State University School of Medicine, Detroit, Michigan.
Ment Retard Dev Disabil Res Rev. 2004;10(2):112-6.
Serotonin abnormalities have been reported in both autism and epilepsy. This association may provide insights into underlying mechanisms of these disorders because serotonin plays an important neurotrophic role during brain development-and there is evidence for abnormal cortical development in both autism and some forms of epilepsy. This review explores the hypothesis that an early disturbance in the serotonin system affects cortical development and the development of thalamocortical innervation, and is a potential mechanism, common to autism and pediatric epilepsies associated with cortical dysplasia. An argument is made that cortical malformation leads to abnormalities of thalamocortical connectivity, and that serotonin plays a critical role in this process. Finally, a role for altered metabolism of the serotonin precursur, tryptophan, in both epilepsy and autism is discussed.

The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function.
Psychol Med. 2003 Nov;33(8):1381-6.
Dieting in healthy women results in a decrease in the availability of tryptophan, the amino-acid precursor of serotonin, for brain serotonin synthesis. This is associated with increases in the prolactin response to serotonin drug challenge suggesting a 'supersensitivity' of serotonin neuroendocrine responses. The aim of the study was to assess whether increased tryptophan intake during dieting would prevent the changes in tryptophan availability and serotonin neuroendocrine function. Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced tryptophan (1.8 g daily) or placebo in a double-blind, parallel group, design. Tryptophan supplementation failed to modify the dieting-induced reduction in fasting tryptophan availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional tryptophan did not show enhanced prolactin responses to intravenous tryptophan challenge. The decrease in tryptophan availability produced by dieting may be due to increased tryptophan metabolism rather than decreased tryptophan intake. While tryptophan treatment did not increase fasting tryptophan availability it may have modified the effect of dieting on brain serotonin function. Further studies will be needed to see if this effect of tryptophan has consequences for the effectiveness of dieting as means of weight control.

Serotonin receptor ligands and the treatment of obesity.

Curr Opin Investig Drugs. 2004 Apr;5(4):377-88.
It was first established in the 1970s that the brain serotonin system was involved in the control of eating. Subsequent progress in the molecular pharmacology of serotonin receptors, and the development of selective serotonin receptor ligands, has clarified our understanding of the role of serotonin  in the regulation of ingestive behavior. Of the 14 serotonin receptor subtypes currently described, 5-HT1A, 5-HT1B and 5-HT2C receptors have been of principal interest in the regulation of food intake. This is largely due to the development of suitable agonists, antagonists and gene-knockout animals with which the role of these receptors can be elucidated. The recent development of selective ligands and knockout mice for other serotonin receptors, including the 5-HT2B and 5-HT6 receptors, has also suggested a role for these receptor subtypes in eating behavior. Studies using such approaches should further our understanding of the role of serotonin in the regulation of feeding behavior and thus, may lead to the development of novel, safe, serotonin receptor ligands for the treatment of obesity.

Aggression: the testosterone-serotonin link.
Be'er Yaakov Mental Health Center, Magen Prison, Ramleh, Israel.
Isr Med Assoc J. 2003 Sep;5(9):653-8.
The relevance of central neurotransmission to aggressive and impulsive behavior has become more evident due to extensive research in humans and animals. Among other findings, there are abundant data relating low serotonin activity--as measured by low cerebrospinal fluid 5-hydroxyindolacetic acid, and a blunted response of prolactin to fenfluramine--to impulsive behavior. Many studies on testosterone activity show a relation between high plasma levels and a tendency towards aggression. It is hypothesized that the interaction between low serotonin and high testosterone levels in the central nervous system has a significant effect on the neural mechanisms involved in the expression of aggressive behavior. It seems that testosterone modulates serotonin receptor activity in a way that directly affects aggression, fear and anxiety. Our survey reviews the main findings on serotonin, testosterone and the possible interaction between them with regard to these behavioral phenomena.

The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function.
Psychol Med. 2003 Nov;33(8):1381-6.
Dieting in healthy women results in a decrease in the availability of tryptophan, the amino-acid precursor of serotonin, for brain serotonin synthesis. This is associated with increases in the prolactin response to serotonin drug challenge suggesting a 'supersensitivity' of serotonin neuroendocrine responses. The aim of the study was to assess whether increased tryptophan intake during dieting would prevent the changes in tryptophan availability and serotonin neuroendocrine function. Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced tryptophan (1.8 g daily) or placebo in a double-blind, parallel group, design. Tryptophan supplementation failed to modify the dieting-induced reduction in fasting tryptophan availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional tryptophan did not show enhanced prolactin responses to intravenous tryptophan challenge. The decrease in tryptophan availability produced by dieting may be due to increased tryptophan metabolism rather than decreased tryptophan intake. While tryptophan treatment did not increase fasting tryptophan availability it may have modified the effect of dieting on brain serotonin function. Further studies will be needed to see if this effect of tryptophan has consequences for the effectiveness of dieting as means of weight control.

Learn more about neurotransmitters

Serotonin, MDMA, Depression, and Ecstasy
Ecstasy, the illegal recreational drug blamed by doctors for depression and anxiety, may often only enhance these symptoms rather than cause them. Dutch researchers found that children who suffered from depression were more likely to go on to use the MDMA drug when they grew up to make them feel better. The appearance later in life of emotional problems in these people might not therefore be primarily due to their use of ecstasy, but could reflect pre-existing conditions.


Email Questions about Serotonin
Q. Is it possible to measure the brain’s serotonin levels via blood tests and if so, how accurate are the results?
   A. Most researchers find that levels of serotonin and other brain chemicals are more accurately measured in spinal fluid as opposed to blood.

Q. Can urine specimens give accurate information regarding serotonin levels? Also, are there any dangers in taking Dr. Sahelian's supplements to raise low serotonin levels?
   A. There are always potential side effects when serotonin or other brain chemical levels are manipulated, especially with high doses of supplements, but when do in a gradual low dose way, it is much safer. We are not sure about urine serotonin levels, we have not heard about this, although we have not looked into it in any detail.

Q. Is there a blood test for serotonin level ?
   A. There is a blood test for serotonin levels in the blood stream, but this test is not routinely available in a doctor's office. Researchers are also able to check the serotonin level in the brain and spinal fluid, but this is complicated and may require a spinal tap. Even if one knows the serotonin level in the blood, this serotonin level may fluctuate throughout the day and basing treatment for depression on the serotonin level in the blood is not practical and probably not effective.

Q. Is Serotonin in food?
   A. There may be small amounts of serotonin in food but this small amount is clinically irrelevant.

Q. What herbs reduce excess serotonin?
   A. First, we have to ask, how do you know you have excess serotonin? Unless a spinal or brain fluid is analyzed, there is no accurate way to determine that a mind or body condition you have is due to excess serotonin. The body and brain and too complicated to think of them in terms of one excess or deficiency of one chemical causing the problem. Having said this, I am not aware of any herb or nutrient that would reduce serotonin levels in the body in a safe way.

Q. Why don't they sell serotonin supplement pills?
   A. Serotonin is not able to easily cross the blood brain barrier, hence either tryptophan or 5-hydroxy-trytophan supplements are good options since they convert into serotonin after going into the brain. You cannot find serotonin pills over the counter or by prescription, the closest supplement to a serotonin pill is 5-HTP.

Q. Both neurotransmitter serotonin and dopamine lift mood, how does one know which to focus on?
   A. Short of spinal fluid analysis - for the neurotransmitters serotonin, norepinephrine, dopamine, and others - which is not practical, it is difficult to know the brain chemicals that are involved in a particular person's depression. Is is serotonin or dopamine or a combination or several other brain chemicals or hormones? All kinds of combinations are possible.

Q. Does 5-HTP help with gambling problem?
   A. It's difficult to predict, but nutrients that influence serotonin levels should be considered in those who have a gambling problem. It's worth trying a ten dollar supplement like 5-HTP for a month or so to see if there is any improvement.

Q. In a clinic in Los Angeles they told me that they are able to prescribe exactly what I need, a missing ingredient, but doing an analysis of urine to determine which of the 6 serotonin producers in the brain I am missing. Is this true?
   A. If this is what they said, I don't agree.

Q. I am looking for a serotonin supplement but can't find one on the internet.
   A. There is no such thing as a serotonin supplement, but there is a nutrient and an amino acid, 5-HTP and tryptophan, than convert into serotonin. In some ways they are indirect serotonin supplements.

Q. I have taken tryptophan off and on for many years - even from Canada when you couldn't get it here - and have never had a problem with it. Recently, a new doctor did a serotonin test on me and it came back at 24, which she told me was very low. I was taking 500 mg of tryptophan at night and was getting good sleep, even tho I was still mildly depressed. I asked the doctor if I should up my tryptophan and she said she could give me a serotonin shot instead. I was hesitant, but she assured me it was safe, so I went ahead with it. About an hour later, I started having a pain across the top of my chest that lasted for about 30 - 40 minutes. Then later that day, I started dropping things. I didn't feel bad - just kinda spacey and so didn't pay much attention. But then either that night or the next, I can't really remember, I woke up with the most horrendous anxiety attack you can imagine. Its been 3 months and I'm better, but still am having a lot of anxiety and depression and don't feel like myself at all. So my regular doctor did a serotonin test and it was 117 which she said was in the normal range so she didn't understand why I was having any problems. But thats almost 5 times what it was when I was sleeping OK and not having anxiety. I wish I would have done what I thought and just taken a little more tryptophan instead of that serotonin shot. Please warn people to be careful about raising their serotonin level too fast and too high for their bodies.
   A. I am not aware of such a thing as a serotonin shot.

 

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