Product Name : 5-HTP (5-hydroxytryptophan or 5-hydroxy-l-tryptophan)
Botanical Source: Griffonia simplicifolia
Country of Origin :
China

5-HTP side effects
5-HTP was introduced to the over the counter market in 1994. Our understanding of 5-HTP's clinical role and its side effect profile is still fuzzy. We don't know as much as we should about the effects of chronic 5-HTP use. Therefore, until we learn more, the idea is to take 5-HTP in the minimum effective dosage and to avoid its prolonged continuous use. I tell my patients who use 5-HTP for depression or other reasons to take frequent breaks to avoid potential 5-HTP side effects (the frequency and length of breaks varies since each person is unique). During these breaks, other forms of therapy could be substituted. As of now, and after more than a decade off 5-HTP being available to the public, I am not aware of any reports in the medical literature of anyone who has encountered life threatening or other serious 5-HTP side effects. It's best to be cautious, limit use to 50 mg or at most 100 mg a day, and take breaks.
Common side effects with 5-HTP include nausea, stomach upset, loose stools or constipation, and headache.

5-HTP Dosage
Some studies have used dosages of 300 mg a day of 5-HTP for depression, but I consider any 5-HTP dose above 50 mg to 100 mg a high dose. Most 5-HTP products on the market are sold in 50 and 100 mg capsules. Some people do well with 20 to 50 mg, while others may temporarily require 100 mg or more. I'm not aware of 5-HTP products on the market that are less than 50 mg. Those who do well with small doses can open a capsule and take a portion mixed with water. 5-HTP is best absorbed on an empty stomach, or some users have tried taking a smaller amount of 5-HTP sublingually, that is, under the tongue. Medical supervision is recommended if high doses of 5-HTP are required to treat a particular condition. I don't recommend the routine use of daily intake doses greater than 100 mg since there's the possibility of nausea or nightmares. Also, we still don't know if there are any long term 5-HTP side effects if people take high doses for many years. 5-HTP enhances dreams and makes them more vivid. Use less than 50 mg in the evening to avoid or reduce nightmares. Some people may find 10 to 30 mg works better. Capsules can be easily opened by pulling on each end.

Safety of 5-HTP
5-Hydroxy-L-tryptophan (5-HTP) is the immediate precursor in the biosynthesis of 5-hydroxy-tryptamine (5-HT; serotonin) from the essential amino acid L-tryptophan. The use of L-Tryptophan as a dietary supplement was discontinued in 1989 due to an outbreak of eosinophilia-myalgia syndrome (EMS) that was traced to a contaminated synthetic L-Tryptophan from a single manufacturer. 5-HTP has since become a popular dietary supplement in lieu of the removal of L-Tryptophan from the market. Because of its chemical and biochemical relationship to L-Tryptophan, 5-HTP has been under vigilance by consumers, industry, academia and government for its safety. However, no definitive cases of toxicity have emerged despite the worldwide usage of 5-HTP for the last 20 years, with the possible exception of one unresolved case of a Canadian woman. Extensive analyses of several sources of 5-HTP have shown no toxic contaminants similar to those associated with L-Tryptophan, nor the presence of any other significant impurities. A minor chromatographic peak (peak X) reported in some 5-HTP samples lacks credibility due to chromatographic artifacts and infinitesimal concentrations, and has raised undue speculations concerning its chemistry and toxicity.
Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004 Apr 15;150(1):111-22. ISSI Laboratories Inc., 515 Blue Ridge Avenue, Piscataway, NJ 08854, USA.

Biochemistry of 5-HTP
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.

Tryptophan converts to 5-HTP which converts to Serotonin, then to N-Acetyl-serotonin, followed by Melatonin. Note: Tryptophan is also metabolized by a different pathway, not all of it is converted into 5-HTP.

From the book Mind Boosters: Conversion of Tryptophan into 5-HTP, Serotonin and Melatonin.

Short term 5-HTP side effects
6-HTP side effects from high doses (which could be 70 to 100 mg and greater) include nausea and vomiting, stomach cramps, nightmares, and decreased sex drive. Serotonin has an inhibitory effect on sexual behavior, therefore, one of the 5HTP side effects is decreased libido. Tiredness and sleepiness can occur after several days or weeks of use, which may indicate that a break should be taken from 5-HTP use. For those who experience nightmares or other 5HTP side effects such as nausea or decreased libido, you may consider taking a lower dose. Here's a report from one user, "Hi, great website. I am writing because I just yesterday took a 100 mg. 5-htp. I feel awful for the most part. I am usually sensitive to any side effects, and I just feel the stomach discomfort and fullness and then feel kind of disoriented and weird."
     Nightmares sometimes decrease after the first few nights.

Long term 5-HTP side effects
Long term side effects with 5-HTP are not fully known. When hundreds of thousands of people start taking a supplement that has not had adequate long-term testing, there may be some individuals who have a biochemical abnormality in metabolizing that nutrient that was previously not known. We don't know the consequences on the immune system, skin, and other tissues of long-term 5-HTP therapy. Regular long term use is not recommended at this time.
     At this point of our knowledge with 5-HTP, it would be best not to use it while trying to become pregnant or during pregnancy. The safety of 5-HTP during lactation and breast feeding is not known.

5-HTP Source and manufacture
5-HTP is made in the body from the amino acid tryptophan. Most of the 5-HTP produced in the body comes from its manufacture in the intestines from tryptophan. Tryptophan is an essential amino acid; that is, the body does not have the capacity to synthesize it. All the supply of tryptophan must be gotten through foods that contain protein.
      5-HTP sold over the counter is extracted from the Griffonia seed. The seeds come from an African tree grown mostly in Ghana and the Ivory Coast. 5-HTP can also be made synthetically in the laboratory. The final product is the same as the one made by the body. Only a small (3 to 7) percent of the griffonia seed is made of 5-HTP, therefore, consuming griffonia seeds is not an efficient way of getting 5-HTP. 5-HTP is not made from fermentation of bacteria.

5-HTP Interactions
The use of 5-HTP for depression in combination with SSRIs such as Prozac, Paxil, Zoloft, and others has not been formally evaluated. Anecdotal reports indicate that many people tolerate small amount of 5-HTP, 50 mg or less, with reduced doses of SSRIs when used under the guidance of a medical professional. The effects of taking 5-HTP for depression along with a pharmaceutical antidepressant are sometimes difficult to predict. Since the SSRIs, like Prozac, block serotonin reuptake, and 5-HTP converts into serotonin, it is possible that dangerously high levels of serotonin could occur, a condition called serotonin syndrome.
     It is difficult to predict the interaction of 5-HTP with lithium, MAO inhibitors, anti-anxiety agents, beta blockers, birth control pills, and other pharmaceutical medicines.
     Some physicians are using a combination of two or more natural antidepressants such as 5-HTP, St. John's wort, SAM-e, and others. However the interactions are not fully known and caution is advised when 5-HTP is used for depression in combination with other supplemetns. Any such combination should be done under medical supervision.

5-HTP Dosage and Timing
It's difficult to say what the best time to take 5-HTP since it varies among individuals. It depends whether 5-HTP is being used for sleep, in that case it is taken in the evening; for anxiety or depression, 5-HTP can be taken any time of day. For weight loss or appetite control, 5-HTP may be taken on an empty stomach an hour or two before a meal.
     If you do take 5-HTP during the day, it's best to keep your 5-HTP dosage to less than 50 mg since sleepiness may occur. 5-HTP is absorbed better taken on an empty stomach.
     There is has not been enough research done with 5-HTP to know the ideal dosage and timing. Also, there is significant individual variability to the response to 5-HTP. Hence, each person may need to find out for himself or herself the lowest 5-HTP dosage that works well, and the ideal timing, whether early in the day, midday or evening.
     A small amount of alcohol usually does not interfere with 5-HTP, but larger amounts may.

Benefit of 5-HTP for Anxiety, 5-HTP for Depression and Sleep
Some people who take 5-HTP notice the benefit of better mood balance, decrease in appetite, reduced anxiety, better impulse control, and better sleep. Try a dose lower than 50 mg for sleep, and 5-HTP is not consistent in inducing sleep. I have come across some individuals who find themselves more alert rather than in a relaxed, sleepy state of mind with 5-HTP.
     Does 5-HTP help with weight loss? Some find that 5-HTP helps curb appetite. This nutrient could be used temporarily for appetite suppression while other lifestyle and dietary changes are being incorporated regarding a life long plan for keeping weight off. Not everyone notices the appetite suppressing effect from 5-HTP. A study in rodents indicates that 5-HTP may be useful in controlling the excessive food intake sometimes generated by stress. Long term human studies are not available to determine whether 5-HTP for weight loss is a good option.
     5-HTP may be temporarily helpful in conditions that normally require prescription antidepressants, anti-anxiety agents, sleeping pills, and weight loss drugs. 5-HTP may also be helpful in some individuals with migraine headaches and fibromyalgia although much more research is needed.
     5-HTP reduces the severity of a panic attack which may indicate that panic attacks may partly be due to low serotonin levels.

5-HTP Research update
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. METHODS: Thirty rats (30 days of age) were used in the survey, measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxytryptophan (5-HTP or l 5-htp), and serotonin (5-HT) after intraperitoneal (i.p.) injections of 4 and 10 mg/kg/day of pyridoxine HCl during 20 days and a single dose of 2 microM/kg (440 microg) of BHT. RESULTS: Levels of TBARS and 5-HTP increased considerably (p <0.05) in all vitamin- and/or BHT-treated groups, and 5-HT increased partially (p <0.05) 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.

5-HTP is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C.
J Pineal Res. 2005 Jan;38(1):62-6.
Hydroxyl radicals are involved in direct damage of important biomolecules. Potent radical scavengers such as vitamin C and indoles of the tryptophan family can avert the potential damage. Melatonin and its precursor 5-hydroxytryptophan ( 5-HTP ) were compared with water-soluble vitamin C.  5-HTP showed highest hydroxyl radical scavenging effects, more than vitamin C, which was more than melatonin.

5-HTP Prevents Panic Attacks -- A panic attack involves the sudden appearance of several symptoms including shortness of breath, sweating or shaking, palpitations, and the fear of dying or losing control. Women are more likely than men to have this condition. Doctors often prescribe anti-anxiety medicines such as Xanax or Valium. However, a nutrient known as 5-HTP may play an important role. 5-HTP stands for 5-Hydroxytryptophan, a supplement available over the counter that, when ingested, goes to the brain and converts into the brain chemical serotonin. Serotonin is known to induce relaxation and balance mood. Researchers at the Department of Neuropsychology at Maastricht University in The Netherlands were able to induce a panic attack in volunteers who suffer from panic disorder by having them breathe a high concentration of carbon dioxide. They repeated the study, this time giving half of the volunteers 200-mg of 5-HTP while the others received a placebo. Those who took 5-HTP had a significantly diminished panic response compared to those on placebo.
     Dr. Sahelian says: 5-HTP is available in health food stores in a dosage of 50 mg. The results of this study are quite interesting and indicate that those with panic attacks may not have adequate levels of serotonin. If you suffer from frequent panic attacks, it would be worthwhile to discuss the findings of this 5-HTP study with your physician.

The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers.
Department of Psychiatry, University of Tartu, Raja, Estonia.
J Psychopharmacol. 2004 Jun;18(2):194-9.
Previous studies suggest a modulatory role of serotonin in experimentally-induced panic attacks. In the current study, we investigated the acute effects of 5-HT precursor l-5-hydroxytryptophan (5-HTP) on the response to panicogenic challenge with cholecystokinin-tetrapeptide (CCK-4) in healthy volunteers. Thirty-two subjects were randomized to receive either 200 mg of 5-HTP or placebo with the CCK-4 challenge following in 90 min in a double-blind, parallel-group design. The results showed a nonsignificant difference between the groups in panic rate (19% after 5-HTP and 44% after placebo, p = 0.13) with a trend for lower intensity of symptoms after 5-HTP (p = 0.08). Further analysis by gender revealed that females in the 5-HTP group had a significantly lower panic rate and intensity of cognitive symptoms whereas, in males, the effect of 5-HTP was limited to lowering the intensity of somatic panic symptoms. Thus, an increased availability of 5-HT may have a gender-dependent protective effect in CCK-4-induced panic.

Single-dose administration of 5-hydroxytryptophan (5-HTP) is regularly used as a challenge test of the serotonergic system. The use of 5-HTP has been limited by an apparent small window between the occurrence of neuroendocrine endpoints and the occurrence of side effects. Therefore, many dosing strategies have been tried with and without concurrent administration of carbidopa, a peripheral inhibitor of the decarboxylation from 5-HTP to serotonin. The aim of the current study was to assess the relation between pharmacokinetics and pharmacodynamics of 5-HTP. Twelve healthy male volunteers were included in a placebo-controlled, randomized, four-way crossover, double-blind, single-dose investigation of oral 5-HTP with or without coadministration of carbidopa. The four dose regimens were placebo, 5-HTP 100 mg, 5-HTP 200 mg, and 5-HTP 100 mg with coadministration of carbidopa 100 mg and 50 mg at 3 hours before and 3 hours after the administration of 5-HTP, respectively. The last regimen resulted in a doubling of the elimination half-life, an apparent clearance at least 14 times smaller, and a 15.4 times greater area under the curve compared with 5-HTP 100 mg without carbidopa. Furthermore, it was the only regimen to induce a significant change in cortisol and prolactin. It did not induce any change in subjective psychologic symptoms or cardiovascular parameters, but it was the only regimen to induce some nausea in three participants. The authors conclude that this regimen of 5-HTP 100 mg plus carbidopa is a relatively simple, effective, and tolerable challenge of the presynaptic serotonergic system.