5-HTP May Improve Serotonin-Dependent Alertness

Serotonin Is a Mood Booster

5-HTP May Improve 
Serotonin-Dependent Alertness

Staying alert may mean staying alive in today's hectic world
By Dr. Edward R. Rosick

uring the last 20,000 years (a mere blink of the eye in the span of evolutionary history), we humans have progressed from being hunters on the plains of Africa and the forests of Europe to creatures who now routinely travel into space. In terms of inherent nature, however, and even outward appearance, a modern man is little different from a Cro-Magnon man of 20,000 years ago - assuming that Mr. C-M had a good shave and a nice Armani suit! (And women, please stifle those rude jokes that are even now coming to mind.)

Of course, the Cro-Magnon man had to face far different daily stresses than we do. Life was short and brutal for our distant ancestors, who were fighting for their very survival every moment of their lives. Having to coexist with ferocious predators, such as the saber-toothed tiger and the monstrous cave bear (which would make today's grizzlies look like adorable teddy bears), the Cro-Magnon hunter could become the hunted at any moment. His motto could well have been "Be alert or die." The "lerts" made it to another day.

Your Brain Is Wired for Survival

Fortunately, being alive in the twenty-first century means that we are unlikely to become fast food for some hungry predator. Yet we still face occasional dangers that require high alertness and quick action. Imagine that you're crossing a busy intersection in heavy traffic (didn't your mother teach you not to do that?). Suddenly you hear the sound of screeching brakes, and out of the corner of your eye, you see a fully loaded SUV barreling down on you - with the driver blabbing on his cell phone, of course. Red alert! Which way do you turn? Which way do you run without getting hit by some other car? Decide! Run! Do it NOW!

Recent work has indicated that
a key player in attention, both
voluntary and involuntary, is the
brain chemical serotonin, which
is derived from 5-HTP.

Whew! Since you're reading this, you must have reacted quickly enough to save your life - congratulations. Your brain is hard-wired, as was Cro-Magnon's, so as to allow you to interact on a subconscious level with your everyday environment, including whatever perils may pop up out of the blue. (If you had to think about every single action you made, it would take hours just to get out of bed: "Which eye should I open first? How many breaths should I take? What sounds should I listen for that could be a sign of danger? What should I do if I hear one?")


Our innate ability to respond to sudden, unexpected stimuli or changes in our surroundings is called involuntary attention shifting, which is just a fancy term for "reacting." Although scientists can't pinpoint the areas of the brain that allow us to perform this vitally important task, they do know from extensive testing done with electroencephalography and magnetoencephalography (EEG and MEG - see the sidebar) that it takes place in the forebrain, which includes the cerebrum, thalamus, and hypothalamus.

EEG and MEG: Viewing the Brain in Action

Pick up any science fiction book about an advanced society of the future, and chances are there will be a description of some type of machine that can literally read a person's mind. Although such machines are still strictly imaginary, there is already equipment being used in hospitals and clinics around the world that can show how a person's brain is working while he or she is thinking.

In 1929, the German psychiatrist Hans Berger developed the world's first electroencephalograph (EEG). Berger's machine, like all other EEG machines after it, recorded the extremely small waves of electrical energy emitted by different regions of the brain (his first subject for these experiments was his young son). Electrodes placed strategically on the person's scalp pick up the waves. When the person thinks, the tiny signals (around 1 microvolt) are sensed by the electrodes, amplified, and displayed on a printer or video monitor as "brain waves."

EEG: Then and Now

Today's EEG machines are much more precise and sensitive than those in the early days. Berger's machine could show only that brain electrical activity changed when the functional status of the brain changed, as in sleep, hypoxia (lack of oxygen), or in certain diseases, such as epilepsy. Today, by simultaneously recording through a large number of electrodes placed in a precise, geometric array on the scalp, researchers can obtain accurate topographic maps of the brain's electrical activity. This helps them deduce what areas of the brain are active when a person is performing certain tasks and how certain drugs affect different areas of the brain. It also enables them to pinpoint areas that are being harmed by conditions such as stroke.

MEG: New Kid on the Block

A newer way to image the inner workings of the brain is with the magnetoencephalograph (MEG), which measures the small magnetic fields associated with the brain's electrical activity. Making the measurements requires that the patient be isolated in a magnetically shielded room so as to avoid interference from extraneous magnetic influences, including those of the earth's own magnetic field, which is about one billion times stronger than the fields produced by a human brain. Unlike an EEG, an MEG machine does not require anything to be attached to the patient's scalp; instead, a device called a biomagnetometer, which looks much like a large x-ray machine, scans the patient's head.

With MEG, researchers are now able to measure the activity of the brain in real time. They can produce detailed maps of the brain, showing just where it is active when a person is alert and attentive. Isn't science wonderful?

5-HTP and Serotonin - Keys to Alertness

Through several different avenues of research, scientists are beginning to unravel the mysteries of human consciousness, including how we stay attentive and focused in a world filled with distractions and potential dangers. Recent work has indicated that a key player in attention, both voluntary and involuntary, is the brain chemical serotonin. This vitally important neurotransmitter is known to be involved in a wide variety of behaviors, including mood, sleep, depression, aggression, and, most importantly (at least for our discussion), attention - specifically, reacting.

Serotonin, also known as 5-hydroxytryptamine, or 5-HT, is produced in the brain from the precursor molecule 5-hydroxytryptophan, or 5-HTP. 5-HTP is an amino acid that is produced from tryptophan, an amino acid found in most food proteins. So the biochemical sequence is tryptophan --> 5-HTP --> 5-HT (serotonin). The amount of serotonin in the brain is firmly linked to the dietary intake of both tryptophan and 5-HTP.

Increasing Serotonin Improves Reaction Time

Many studies on the effect of serotonin levels on attention have focused on a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), which increase the effective levels of serotonin in the brain. A small study in 1997 showed that volunteers given a single dose of an SSRI had quicker reaction times than volunteers given a placebo.1 Another study done in 2000 looked at the effects of a single dose of an SSRI or placebo on the cognitive and psychomotor performances of nine male volunteers.2 As in the earlier study, the men who received the SSRI had improved attention and reaction time compared with the men on placebo.

Decreasing Serotonin Impairs Reaction Time

Since increasing serotonin levels seems to improve attention, researchers have sought confirmation of this effect by looking at the other side of the coin: they want to know what happens when serotonin levels are decreased. This can be done by restricting dietary intake of the serotonin precursor tryptophan and thus, by extension, of its closer precursor 5-HTP.

A small, double-blind, placebo-controlled study examined the effects of a tryptophan-free drink on cognitive processing in 12 healthy young women.3 After a 24-hour period with low tryptophan intake and an overnight fast, the women were given one of two drinks that were balanced with regard to amino acid content except for tryptophan: one drink contained no tryptophan, and the other was fortified with 1.9 grams of it.

The women's blood tryptophan levels were measured 7 hours after ingesting the drinks, and cognitive testing was done immediately after that. As expected, the blood tests showed that the tryptophan-free drink significantly lowered the women's tryptophan levels and, therefore, their serotonin levels. In these women, the reaction times on standardized tests were significantly slower than in the women who had taken the tryptophan-fortified drinks.

Low Serotonin = Slow Reaction

Another recent study examined the effects of decreased serotonin levels on reaction time.4 In this double-blind, placebo-controlled study, 13 healthy volunteers (7 men and 6 women) were given either a balanced amino acid drink or one that caused acute tryptophan depletion (ATD). Blood samples taken 5 hours later showed that total tryptophan levels in the volunteers who had taken the ATD drink had dropped by 75%.

To test for reaction time, the researchers subjected the volunteers to a random sequence of tones, after instructing them to distinguish between different durations of the tones and to press a button as rapidly as they could after each tone. (This kind of test is considered to be safer than shoving the volunteers into oncoming traffic and seeing how they fare, but the principle is the same: reaction time matters.) EEG and MEG data were also recorded in the volunteers during their reaction-time testing.

5-HTP easily crosses the blood-
brain barrier and can effectively
increase the amount of serotonin
produced in the brain.

The results of this study were similar to those of the previous tryptophan-depletion study, in that the volunteers who had consumed the ATD drink had slower reaction times. Out on the road, whether as a pedestrian or as a driver, this factor could spell the difference between life and death.

Moreover, significant changes were observed in both the EEG and MEG readings of the ATD volunteers. The authors concluded that "The MEG and EEG results suggest that the reduction of the brain 5-HT [serotonin] function by ATD may delay automatic change detection at the auditory cortex and thus impair initiation of involuntary attention shifting . . . ."

In other words, low serotonin means slow reaction.

5-HTP - A Safe, Natural Route to More Serotonin

Although further research is needed, it doesn't seem like too great a leap of faith to think that people might increase their alertness by boosting their brain serotonin levels. One way to do this is by taking SSRIs - the disadvantages being that these drugs are available only by prescription, they're expensive, and they can have some undesirable side effects, such as nausea, headaches, and significant interference with sexual functioning.

A safer and more natural way to increase serotonin levels may be to supplement with serotonin precursors. Tryptophan itself is not available as a nutritional supplement, owing to a misguided FDA ruling, but 5-HTP is available, and it is well absorbed, with 70% of the amount ingested ending up in the bloodstream. 5-HTP easily crosses the blood-brain barrier and may effectively increase the amount of serotonin produced in the brain.5

Faster Reaction Time May Help Keep You Alive

It's safe to say that most people alive today would rather live here and now than 20,000 years ago. Even though we no longer have to worry about being the "meal du jour" for a saber-toothed tiger, we still face hazards in our technologically advanced world that can cause us as much harm as the teeth and claws of any animal. Supplementing with 5-HTP may help improve your reaction time so that you can more safely cope with the hazards of the modern world and live to enjoy another day.


  1. Hasbroucq T, Rihet P, Blin O, Possamal CA. Serotonin and human reaction processing: fluvoxamine can improve reaction time performance. Neurosci Lett 1997;229(3):204-8.
  2. Nathan PJ, Sitram G, Stough C, et al. Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor. Behav Pharmacol 2000;11(7-8):639-42.
  3. Murphy FC, Smith KA, Cowen PJ, et al. The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers. Psychopharmacol 2002;163:42-53.
  4. Ahveninen J, Kahkonen S, Pennanen S, et al. Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans. NeuroImage 2002;16:1052-61.
  5. Birdsall TC. 5-Hydroxytryptophan: a clinically effective serotonin precursor. Alt Med Rev 1998;3(4):271-80.

Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master's degree in healthcare administration.

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