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Clarifying the Complex World of Nutrition Science

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5-HTP: The Natural Alternative to Prozac® - Section 5

Improving Sleep

One of tryptophan's primary claims to fame has long been its ability to improve sleep in a natural, non-druggy way, and early evidence indicates that 5-HTP may work just as well.43 In fact, the compounding pharmacies we contacted report that most of the 5-HTP prescriptions they receive are for sleep promotion.

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The level of serotonin in the brain appears to be an important variable in the sleep equation, although the research has a ways to go before scientists really understand the relationship. A few facts are clear, though. First, decreasing serotonin levels in the brain disrupts normal sleep patterns.44 On the other hand, raising serotonin levels, by taking either tryptophan, 5-HTP, or an SSRI, generally promotes sleep.

In its ability to promote sleep naturally, without the drugged feeling and morning hangover often associated with the use of powerful sedative hypnotic drugs like the benzodiazepines or barbiturates, tryptophan and 5-HTP are similar to the hormone melatonin, which is also well-known for its sleep-regulating function. This may not be a coincidence, because some of the serotonin produced in the body is converted directly into melatonin. Animal studies show that taking tryptophan supplements increases the level of circulating melatonin, and there's no reason to believe that the same thing does not happen in humans.45 Thus, at least part of the sleep-inducing effect of serotonin precursors may be due to increased melatonin.

While most of the scientific evidence concerning serotonin and sleep induction has involved tryptophan and SSRIs, a few studies, not to mention countless anecdotal reports, indicate that 5-HTP may be just as effective. In one Norwegian experiment in which cats received injections of either 5-HTP or tryptophan, for example, both treatments produced a "general deactivating effect on the waking state." In a French study, administration of 5-HTP to people described as "mildly insomniac" resulted in significant improvement.46 

Given the long-acknowledged role of tryptophan for promoting sleep, it is a little surprising that so little quality research has been done on 5-HTP and sleep. Nevertheless, that which has been done, plus many anecdotal accounts, leaves little doubt that 5-HTP can be very helpful for promoting sleep.

Because 5-HTP may make you sleepy, it is usually best to take it at bed time, especially if you're taking a high dose (200-300 mg or more). If you find that 5-HTP makes you sleepy, do not take it if you need to drive a car, operate heavy machinery, or do anything else that requires you to be awake and alert.

Paradoxically, some people find that taking 5-HTP at bedtime causes insomnia. It is not known why this happens, but it reinforces the idea that individuals need to experiment with the dosages and scheduling to find that which works best for them. See Chapter 11 for more on dosing.

Losing Weight

According to the British obesity expert, Dr. JE Blundell, among the most effective and safest candidates for drugs that genuinely suppress appetite are those that increase serotonin levels in the brain.47 Not surprisingly, one of the most common uses for SSRIs these days has been to suppress appetite with the goal of losing weight.

Laboratory studies uniformly demonstrate a suppression of eating behavior in laboratory animals treated with 5-HTP. Blundell, for example, found that administration of 5-HTP reduced food intake both in free-feeding rats and in hungry rats that had been deprived of food.48 In another study in laboratory rats, 5-HTP reduced food intake by nearly 70%.49 

Although much human research still needs to be done with 5-HTP and appetite suppression, it appears that the primary effect of 5-HTP and other serotonin-enhancing agents is to decrease the craving for carbohydrates.50 In one small, but well-controlled trial, 20 obese individuals were randomly assigned to receive either a high dose of 5-HTP (900 mg/day) or placebo.51 The trial lasted 12 weeks. During the first 6 weeks, the subjects ate as they usually did, with no restrictions. During weeks 7 through 12, they were placed on a restricted calorie diet.

The researchers reported significant weight loss in the 5-HTP-treated group, but not in the placebo group (Fig. 11). Weight loss, which was associated with reduced carbohydrate intake and early satiety, accelerated dramatically for the 5-HTP-treated subjects during the restricted diet phase of the study, suggesting that 5-HTP helped these people stay on their diets. The effectiveness of 5-HTP in reducing food intake along with its relative lack of serious side effects led the authors to conclude that it may be safely used to treat obesity.

How Safe is 5-HTP?

When taking any substance that alters the body's neurochemistry, it is always important to proceed with caution, and 5-HTP is no exception. It is almost inevitable that too high a dose will cause adverse effects, and it is possible that some of these could be serious. Having said this, we should point out that 5-HTP is an exceptionally safe nutritional supplement that has rarely, if ever, been associated with serious problems.

GI Upset

The most common side effects associated with oral 5-HTP are generally related to gastrointestinal upset, including nausea, vomiting, heartburn, and stomach pain. For most people, these tend to be mild and transient. Oral 5-HTP at doses of 100 to 300 mg/day has never been reported to cause significant changes in blood, liver, lung, metabolic, or kidney function.23 

As we noted earlier, for example, the Pöldinger et al study, which compared 5-HTP with the SSRI fluvoxamine in people with depression, found that the SSRI-treated subjects experienced significantly more, and more severe, adverse effects than did those treated with 5-HTP. Overall, the authors stated, "5-HTP-induced adverse events worthy of note are rare within the therapeutic dose range."10 

5-HTP may sometimes cause GI upset, because serotonin (produced from 5-HTP) is a major neurotransmitter in the gut. It has therefore been suggested that people taking oral 5-HTP should also take a drug like carbidopa (called a peripheral decarboxylase inhibitor, or PDI) that prevents the metabolism of 5-HTP to serotonin in the periphery but not in the brain and spinal cord. As a result, less serotonin is produced in the periphery to upset the GI system, and more 5-HTP is made available in the brain to make more serotonin where it is needed most. In essence, the use of a PDI means that a lower dose of 5-HTP can go a much longer way.

Is a PDI really necessary, though? Probably not. 5-HTP has been combined with a PDI in some studies and has been given alone in others. Either way it still raises serotonin levels in the brain, although you may need less 5-HTP when combined with a PDI. A Swiss study of 25 depressed patients found no difference in antidepressant efficacy between those who took 5-HTP alone and those who took it in combination with a PDI. Although the 5-HTP group experienced somewhat more GI side effects, the 5-HTP + PDI group had more psychopathological side effects, such as acute anxiety.52 

Thus, one would have to ask, why add another drug (which requires a prescription) to your regimen if you can get the same therapeutic benefit without it? Of course, if you find 5-HTP's GI side effects to be intolerable, you may want to consult with your physician about trying one of these drugs.

It has also been suggested that 5-HTP may cause GI upset directly by irritating the stomach lining.53 If so, then another possible means of reducing GI side effects may be to take 5-HTP in the form of enteric coated tablets, which dissolve only in the intestine. This is the form that Pöldinger group used and which resulted in very few side effects, but they are not readily available in the US.

Is Serotonin Syndrome a Concern?

Serotonin syndrome is a potentially serious disorder caused by the availability of too much serotonin in the body.5455 Symptoms include confusion, fever, shivering, sweating, diarrhea, muscular incoordination, exaggerated reflexes, and violent muscular contractions. Although serotonin syndrome has occasionally caused death, most people make a full recovery, once the causative agents are removed.

The drugs most commonly associated with serotonin syndrome are those that block the normal metabolism of serotonin -- the MAO inhibitors, the SSRIs, and the tricyclic antidepressants -- and thus increase its availability at certain serotonin receptors. Serotonin syndrome rarely if ever occurs when these drugs are taken by themselves. Rather, it is combinations, such as an SSRI plus an MAO inhibitor, or one of these drugs plus tryptophan, that most increases the risk of serotonin syndrome.

There have been no published reports of serotonin syndrome occurring in someone taking 5-HTP. Nevertheless, there is no reason to think that, given the right combination of drugs and doses, it could not occur. Common sense would dictate, therefore, that 5-HTP be combined with drugs known to affect serotonin metabolism only with the greatest of care and under the supervision of a knowledgeable physician. (See Chapter 11: 5-HTP Dosing Guidelines.)

Other Safety Concerns

Concern has been raised by some people that 5-HTP might increase the risk of a heart attack by enhancing the tendency of blood platelets to clot or by causing coronary arteries to go into spasm. Although it is unclear what the origin for this theoretical concern is, the facts speak for themselves. There has never been a single published report of 5-HTP causing a heart attack. The risk, if it exists at all, would seem to be extremely small and could probably be counteracted by a sensible nutritional program that includes supplements known to reduce platelet aggregation and coronary vasospasm, including vitamins C and E, calcium, magnesium, fish oil, and low-dose aspirin. Other concerns related to the concomitant use of vitamin B6 and the promotion of heart muscle and valve fibrosis by 5-HTP also seem to have no basis in fact.

It is conceivable that these problems could arise if there were excess peripheral serotonin. But, since very little serotonin is produced from 5-HTP outside of the central nervous system, the danger seems remote at best.

5-HTP Dosing Guidelines

The dose of 5-HTP that has most often been reported in the scientific literature and prescribed by physicians is 300 mg per day. When taking 5-HTP for depression, anxiety, or fibromyalgia, the general practice in scientific studies has been to take 100 mg three times a day. This dosing regimen may leave some people too sleepy during the day, however.

Some physicians have found it best to start their patients out by taking 150 to 200 mg at bedtime. If this is insufficient to provide antidepressant/anti-anxiety relief, they can take additional doses of 33 to 50 mg during the day. The number of these doses should be adjusted to a level that provides adequate relief without causing daytime sedation.

If you are taking 5-HTP to enhance sleep, it is probably best to take the entire 300-mg dose at bedtime. The dose used in the best migraine study was 400 mg (100 mg four times per day).34 The dose found to effectively suppress appetite was 900 mg per daily (300 mg three times per day).51 Incidentally, the fact that this very high dose of 5-HTP was used without significant side effects can be taken as an indication of the general safety of this substance.

Different individuals may require higher or lower doses than these, but these are good starting points. As with any drug, it is usually better to start with a low dose and increase it gradually. If you find that a lower dose delivers the therapeutic effect you are looking for, then you can stop there. If the 300-mg dose seems inadequate, you can slowly increase it (preferably under your physician's supervision). In any case, always be alert for adverse side effects. If a given dose makes you feel uncomfortable, either physically or mentally, back off the dose and do not go any higher until you consult with a knowledgeable physician. In most cases, lowering the dose will quickly cause the adverse effects to disappear.

What About Taking 5-HTP With Prozac or Other Drugs?

Although basic dosing of 5-HTP is fairly straightforward, it becomes significantly more complicated if you are currently taking other drugs that affect serotonin levels, such as an SSRI (eg, Prozac, Luvox, Paxil, Effexor, Zoloft), a tricyclic antidepressant (eg, Elavil, Tofranil, Pamelor), or St. John's wort. If you are taking one of these drugs and want to switch to 5-HTP, it is recommended that you first consult with your physician, because taking them together can cause a potentially dangerous elevation of serotonin levels. Never attempt to combine 5-HTP with any of these drugs without the help of a physician.

It is usually necessary to gradually lower the dose of your SSRI (or other drug) as you gradually increase the dose of 5-HTP. Since each individual is likely to react differently to a given combination of doses, your physician will probably want to monitor your responses to these drug combinations very closely. If you experience any symptoms of serotonin overload, such as confusion, fever, shivering, sweating, diarrhea, muscular incoordination, exaggerated reflexes, or violent muscular contractions, the dose of one or both agents can be easily and safely adjusted until the symptoms disappear. Eventually, the SSRI can be completely eliminated. 

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I have been taking 50 mg of venlafaxine twice daily for chronic depression and as a possible treatment for insomnia, as my doctor suggested having resulted from a mood disorder.  My prescription is for 50 mg. 3 times daily but twice daily has been sufficient for my depression.  I have been suffering more of insomnia with it gradually becoming worse in the past 2 1/2 years.  I began taking lunesta intermittently with benedryl and lately now only either benedryl or 25 gm of doxylamine succinate but neither of these seem to work any longer.  I am wondering if it would be safe to take 5 HTP at bedtime instead of the 50 mg. of venlafaxine or should I switch completely to 5 HTP and what is the best way to accomplish this?  Is there any benefit to using 5 HTP long term versus venlafaxine? Or can either be taken safely for the rest of my life if necessary?  What are the actual dangers of long term use of venlafaxine? If 5 HTP will give me a night’s sleep it would definitely be worth it to switch to this or whatever you would recommend.  I would appreciate any additional comments you can make.  Your site has had the best information I have found so far on 5 HTP.  Thank you!

I have had chronic insomnia for the last two years.  I was averaging between a 1/2 hour and 2 hours per night and usually 1 day per week where I would just crash for 10 hours.  I tried 5-HTP three weeks ago (3 100mg before bed) and on the third day of taking it I had the best night of sleep I’ve had in years.  I’ve only had one night of insomnia since that time.  I hope it keeps working.  Insomnia is hell.


In today’s busy society, it’s almost a badge of honour to claim that you get too little sleep. In fact, the average person sleeps 60 to 90 minutes less than they did 50 years ago. Thirty-five to 40 percent of the North American adult population has problems with falling asleep or with daytime sleepiness. “It’s a big problem,” says Lawrence Epstein, MD, regional director for the Harvard-affiliated Sleep Health Centers and author of The Harvard Medical School Guide to a Good Night’s Sleep. “People don’t think sleep is important because we can get by with less, but we’re putting our health at risk.”

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