5-Hydroxytryptophan side effects, dosage, benefits, safety, 50 mg and 100
mg, for depression, mood, weight loss, sleep, stress and
Ray Sahelian, M.D.
January 2 2015
Is there a natural supplement that
can give you similar benefits as SSRI drugs but with fewer side effects?
5-Hydroxytryptophan is a natural supplement that converts in the brain
into serotonin, an important brain chemical involved in mood,
behavior, appetite, and sleep. Serotonin is also involved in impulse
control. For instance, low serotonin levels may lead to addictive behavior
such as gambling or other habits caused by weak will power. Serotonin is
found in many places in the body particularly the brain,
gastrointestinal system, and blood cells.
Some people are deficient in serotonin and hence 5-Hydroxytryptophan may be helpful to them whereas other people may have depression, anxiety, and other symptoms that may appear to be due to serotonin deficiency, but may actually be from other causes. Other nutrients and herbs that have an influence on stress or anxiety include passion flower, tryptophan, kava, theanine, taurine, and valerian. Good Night Rx is quite helpful in most people to induce and maintain sleep, and it works well for sleep. 5-hydroxytryptophan can help some people reduce their food cravings. Other supplements that could may reduce appetite include green tea extract and hoodia.
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5-Hydroxytryptophan side effects,
safety, caution, risks, is it dangerous?
This nutrient was introduced to the over the counter market in 1994. We don't know as much as we should about the effects of chronic use. Therefore, until we learn more, the idea is to take it in the minimum effective dosage and to avoid its prolonged continuous use. As of now, and after more than two decades off 5-Hydroxytryptophan being available to the public, we are not aware of any reports in the medical literature of anyone who has encountered life threatening or other serious 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 include nausea, stomach upset, loose stools or constipation, and headache.
5-Hydroxytryptophan 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
those who experience nightmares or other adverse reactions such as nausea or
decreased libido, you may consider taking a lower dose.
Nightmares sometimes decrease after the first few
Long term side effects are not fully known. We don't know the consequences on the immune system, skin, and other tissues of long-term therapy. Regular long term use is not recommended at this time.
50 mg, 100 mg or 300 mg, is there a danger with too high a dose?
Some studies have used dosages of 300 mg a day for depression, but I consider any dose above 100 mg a high dose. Most 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. Those who do well with small doses can open a capsule and take a portion mixed with water. This nutrient is best absorbed on an empty stomach, or some users have tried taking a smaller amount sublingually, that is, under the tongue. Medical supervision is recommended if high doses are required to treat a particular condition. Some people may find 10 to 30 mg works better. Capsules can be easily opened by pulling on each end.
Some website say that a person can take up to 900
mg a day, this seems quite high to me.
Researchers have given as high as 300 mg three times a day, but most people do very well with 50 mg or 100 mg a day.
Timing, when to take
It's difficult to say what the best time to take it 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, take it any time of day. For weight loss or appetite control, 5-Hydroxytryptophan may be taken on an empty stomach an hour or two before a meal. If you do take it during the day, it's best to keep your dose to less than 50 mg since sleepiness may occur. This nutrient is absorbed better taken on an empty stomach.
There is has not been enough research to know the ideal timing. Also, there is significant individual variability. Hence, each person may need to find out for himself or herself the lowest dosage that works well, and the ideal timing, whether early in the day, midday or evening.
Safety as discussed in the 2004
issue of Toxicology Letters
5-Hydroxy-L-tryptophan is the immediate precursor in the biosynthesis of 5-hydroxy-tryptamine (5-HT; serotonin) from the essential amino acid L-Tryptophan. No definitive cases of toxicity have emerged despite the worldwide usage for the last 20 years. Extensive analyses of several sources have shown no toxic contaminants similar to those associated with L-Tryptophan, nor the presence of any other significant impurities.
At this point of our knowledge, it would be best not to use it while trying to become pregnant or during pregnancy. The safety during lactation and breast feeding is not known.
The use of 5-Hydroxytryptophan 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 a small amount, 50 mg or less, with reduced doses of SSRIs. The effects of taking it for depression along with a pharmaceutical antidepressant are sometimes difficult to predict. Since the SSRIs, like Prozac, block serotonin reuptake, and 5-Hydroxytryptophan converts into serotonin, it is possible that dangerously high levels could occur, a condition called serotonin syndrome.
It is difficult to predict the interaction of 5-Hydroxytryptophan 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-Hydroxytryptophan, St. John's wort, SAM-e, and others. However the interactions are not fully known and caution is advised when it is used for depression in combination with other supplements.
A small amount of alcohol usually does not interfere with 5-Hydroxytryptophan, but larger amounts may.
Gastroenterology. 2009. Estrogen rapidly modulates 5-hydroxytrytophan-induced visceral hypersensitivity via GPR30 in rats.
Benefit for anxiety and sleep
Some people who take 5-hydroxy-l-tryptophan 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. It 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. Another supplement that could help with sleep is theanine.
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, 5-Hydroxytryptophan may play an important role. 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 while the others received a placebo. Those who took 5-Hydroxytryptophan had a significantly diminished panic response compared to those on placebo.
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.
In the current study, we investigated the acute effects of 5-HT precursor l-5-hydroxytryptophan on the response to panic inducing challenge with cholecystokinin-tetrapeptide (CCK-4) in healthy volunteers. Thirty-two subjects were randomized to receive either 200 mg of 5-Hydroxytryptophan or placebo with the CCK-4 challenge. The results showed a nonsignificant difference between the groups in panic rate (19% after 5-Hydroxytryptophan and 44% after placebo) with a trend for lower intensity of symptoms after 5-Hydroxytryptophan . Further analysis by gender revealed that females in the 5-Hydroxytryptophan group had a significantly lower panic rate and intensity of cognitive symptoms whereas, in males, the effect 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.
Weight loss and
Does 5hydroxy tryptophan help with weight loss? Some find that it 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. A study in rodents indicates that 5-Hydroxytryptophan may be useful in controlling the excessive food intake sometimes generated by stress. Long term human studies are not available to determine whether it is a good treatment for weight loss.
5-Hydroxytryptophan may be temporarily helpful in conditions that normally require prescription antidepressants, anti-anxiety agents, sleeping pills, and weight loss drugs. It may also be helpful in some individuals with migraine headaches and fibromyalgia although much more research is needed.
This supplement reduces the severity of a panic attack which may indicate that panic attacks may partly be due to low serotonin levels.
Role of the vitamin B6
Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain.
Arch Med Res. 2004.
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 (30 days of age) were used in the survey, measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxytryptophan and serotonin (5-HT) after intraperitoneal injections of 4 and 10 mg/kg/day of pyridoxine HCl during 20 days and a single dose of BHT. Levels of TBARS and 5-Hydroxytryptophan increased considerably in all vitamin- and/or BHT-treated groups, and 5-HT increased partially only in B6 with or without BHT-treated groups compared with control group. Results suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-Hydroxytryptophan.
ACS Synth Biol. 2014. Precursor-Directed Biosynthesis of 5-Hydroxytryptophan Using Metabolically Engineered E. coli. A novel biosynthetic pathway was designed and verified reversely leading to the production of 5-hydroxytryptophan (5-HTP) from glucose. This pathway takes advantage of the relaxed substrate selectivities of relevant enzymes without employing the unstable tryptophan 5-hydroxylase. First, high-titer of 5-HTP was produced from 5-hydroxyanthranilate (5-HI) by the catalysis of E. coli TrpDCBA. Then, a novel salicylate 5-hydroxylase was used to convert the non-natural substrate anthranilate to 5-HI. After that, the production of 5-HI from glucose was achieved and optimized with modular optimization. In the end, we combined the full pathway and adopted a two-stage strategy to realize the de novo production of 5-HTP. This work demonstrated the application of enzyme promiscuity in non-natural pathway design.