A Powerful Preventive Tool for Children at Risk for Migraine

There have not been enough studies in the scientific literature on nutrients, herbs, and other supplements that use either healthy or young subjects. This is true for several reasons (see Drugless Children - June 2000), not the least of which is that most biomedical journals are biased toward pathology and not focused on achieving optimal health. Therefore it is difficult, if not impossible, to know the full potential of a nutrient - what it can add to our life - unless we know what it can do for healthy and, preferably, young individuals. With only partial evidence, we might miss out on a nutrient that could greatly enhance our life - possibly enhancing inherent protective or restorative powers to new levels - if only we knew its applicability sooner rather than later. To build a better foundation for our nutritional health consciousness and wisdom, we need more information, across a wider age range, about how best to use nutrients to enhance our well-being.

A Major Study Ignored by the Health Press
It is refreshing, therefore, to see more studies appearing in the literature that explore further reaches of human potential, focusing on advantages rather than pathology. These studies, mostly of European and Asian origin, have tested phytonutrients and other nutrients on healthy children and adolescents, providing insights into the nature of our own physiology and allowing us to speculate more confidently about what we can expect as we age. We have recently reported that a phytonutrient used in the treatment of Alzheimer's disease, huperzine A (see also this article), is also beneficial for cognitive enhancement in healthy adolescents.1 In the present article, we describe a major study, largely ignored by the mainstream health press, in which the natural amino acid 5-HTP (5-hydroxytryptophan) was given to migraine-predisposed but otherwise healthy, 5-year-old Italian children, who were selected with parental consent.2

The study, concerned with the mechanisms of pain transmission, found that 5-HTP can help prevent the development of hyperalgesia - an abnormally high sensitivity to pain - and migraine. According to the authors, migraine is a possible consequence of hyperalgesia. In the children's story "The Princess and the Pea," the princess was so sensitive to pain that she could still feel the pea, no matter how many mattresses separated her from it. Think of hyperalgesia as "Princess and the Pea" Pain.

Four hundred thirteen healthy children (214 girls and 199 boys) with a mean age of 5.2 years  were selected, with parental consent, to participate in a double-blind, placebo-controlled, prospective study. The study was approved by the University of Florence, and the children were required to meet the following criteria:

  1. They had to be healthy,
    with no known experiences of the type of pain indicating the development of hyperalgesia, in which a reduction of the pain threshold leads to excessive sensitivity to pain.
  2. They had to have one or more genetic risk factors
    associated with inheritable hyperalgesia.
  3. They had to have one or more serotonergic risk factors,
    such as recurrent abdominal pain, growing pain, hyperactivity, attention deficit, sleep abnormalities, or kinetosis (motion sickness) associated with migraine.

In the selection process, the children were excluded from the study if they had any measure of disease or if they suffered from clinical anxiety or depression. Before the administration of 5-HTP or placebo began, they were given tests to determine their pain thresholds, to establish baselines.

The researchers created, by random selection, a control group of 206 (108 girls and 98 boys) and a test group of 207 (106 girls and 101 boys), matched by age and sex. For three consecutive years at bedtime, the control group received placebo (100 mg of vitamin C), and the test group received 5-HTP (100 mg/day for those up to 5 years of age, and 200 mg/day for those 6 years or older).

The Italian study is the first to
show that 5-HTP can prevent
the development of migraine
syndrome in those who are
predisposed to it.

During the period of the study, the children were evaluated for both behavioral and sensory changes, including growing pains and abdominal pains. Behavioral observations were provided by parents and teachers, and by the boys and girls themselves.

All the children were given routine blood tests by their family doctors at the beginning of the trial, then once a year for the three years of the study and for 17 more years of follow-up. The doctors were asked to record any possible side effects of the 5-HTP, and parents were instructed to help their children record diary information once a week during the first five years. In the event that migraines exceeded one per month, the investigators in this study were to be informed. At the end of the 20-year investigation, all the "children" were interviewed by phone or in person.

It was found that 5-HTP protected the children from the development of migraine syndrome. In the placebo group, 26.6% of the children had migraines more than once per month, on average, while in the 5-HTP group, only 1.4% did. The results were very clear: 5-HTP markedly reduced the occurrence of migraine.

The only side effect reported by the subjects taking 5-HTP was stomachache, of which there were 41 instances during the entire three-year trial. In the placebo group, there were only 10 instances of stomachache, but also 118 instances of nausea and 78 of abdominal pain. This is not inconsistent with the very few side effects other studies have reported by those taking 5-HTP. These results may be explained by 5-HTP's ability to reduce hypersensitivity to pain. Moreover, in the study, eosinophilia (elevation of the special white blood cells associated with inflammation) was not reported in the 5-HTP group; in the control group, there was one case.

Adding power to the study's conclusions is the dominance of Dr. Sicuteri in the field. He is the editor of ten books on primary headache, the discoverer of drugs to treat migraine and cluster headache, and the holder of academic and professional status in the world of pain and headache therapy. The current study upon which this article is based is included in the proceedings of the Ninth Meeting of the International Study Group for Tryptophan Research (ISTRY), held at the University of Hamburg in October 1998. These proceedings were edited by a group of distinguished researchers, including Dr. Gerald Huether.

5-HTP : A Preventive Tool
Other studies have shown that 5-HTP can relieve migraine,3 but the Italian study is the first to show that 5-HTP can prevent the development of migraine syndrome in those who are predisposed to it. To the best of the researchers' knowledge, no other drug or nutrient has ever been shown to do this, thereby preventing a life of chronic and debilitating pain.

5-HTP is as effective as or better than
a state-of-the-art antidepressive drug
(the SSRI fluvoxamine) in treating
patients with clinical

Migraine and major depression are related, according to epidemiologicstudies. Seeking to clarify the underlying mechanisms, researchers examined this relationship in a random sample of 1007 young adults (21-30 years of age).3 They were interviewed in 1989 and again (most of them) 3.5 years later, in 1992. A pattern was observed indicating that the relative risk for major depression was higher in those who had a prior history of migraine, and vice versa. The incidence of migraine was more than four times higher in the women than in the men.

The researchers claim that this is the first time that a causal connection between migraine and major depression has been established that results from bidirectional influences. This means that each disorder increases the risk for first onset of the other. In other words, having depression predisposes one to migraine, and vice versa. This undermines the idea that the connection is psychological - an explanation that would be plausible only if the researchers had found a one-directional effect from migraine to depression. The researchers concluded that there is no simple explanation for the migraine/depression connection and that it is probably biochemical in nature, indicating that supplementation is a plausible solution.

In another, more recent, controlled study done by the same researchers of the bidirectional-influences study cited above, subjects (ages 25 to 55 years) with migraine or other severe headaches were found to have a significantly higher lifetime prevalence of major depression - approximately three times higher than the controls.4

The best explanation of how 5-HTP, a chemical precursor of serotonin, works to treat migraine is that it boosts serotonin levels. A deficiency of this neurotransmitter is believed to underlie the cause of migraine. Although the mechanisms of migraine are far from fully understood, excessive dilation of blood vessels in the head is thought to cause the throbbing or sharp, pounding pain, which is synchronized with the heartbeat as it pumps blood through the arteries. Serotonin acts to constrict blood vessels and relieve pain, but only when present in sufficient amounts.

5-HTP also enhances the body's own pain-relief system, because serotonin controls the manufacture and release of beta-endorphins, which block pain signals in the nerves.5

5-HTP as Antidepressant
Serotonin serves the body in ways that make it indispensable in the prevention of depression, as various studies have demonstrated. Because of its nature as an inhibitory neurotransmitter in the body, serotonin buffers and modulates impulses, especially excessive ones. It can be thought of as the body's natural braking system. A group of Swiss and German psychiatric researchers, headed by Dr. W. Pöldinger of the University Psychiatric Clinic in Basel, Switzerland, has even shown that 5-HTP is as effective as or better than a state-of-the-art antidepressive drug (the SSRI fluvoxamine) in treating patients with clinical depression.6

It is becoming increasingly apparent that psychological depression is a major contributor to morbidity and mortality from heart disease, on a par with more familiar risk factors, such as poor diet, lack of exercise, high blood pressure, high stress, and cigarette smoking. Add to these the finding that anything you can do to minimize or eliminate serious depressive episodes, whether using antidepressants or 5-HTP, may also help reduce your risk of a heart attack. And when you now add migraine prevention and the prevention of depression, the choice should be obvious. The abatement of many of these problems, including their possible solution, may be as simple taking the natural and safe serotonin precursor 5-HTP.


  1. Sun QQ, Xu SS, Pan JL, Guo HM, Cao WQ Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Acta Pharmacol Sin 1999 Jul;20(7):601-3.
  2. Nicolodi M, Sicuteri F. L-5-Hydroxytryptophan can prevent nociceptive disorders in man. Adv Exp Med Biol 1999;467:177-82.
  3. Breslau N, Davis GC, Schultz LR, Peterson EL. Joint 1994 Wolff Award Presentation. Migraine and major depression: a longitudinal study. Headache 1994 Jul-Aug;34(7):387-93.
  4. Breslau N, Schultz LR, Stewart WF, Lipton RB, Lucia VC, Welch KM. Headache and major depression: is the association specific to migraine? Neurology 2000 Jan 25;54(2):308-13.
  5. Battistella P, Bordin A, Cernetti R, et al. Beta-endorphin in plasma and monocytes in juvenile headache. Headache 1996;36:91-4.
  6. Pöldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24:53-81.

In cases of chronic recurrent headaches,
it is vital to rule out any major underlying
illness, such as cancer or a brain tumor.
Factors that trigger headaches should be
eliminated or reduced, including food allergies,
histamine-releasing and histamine-containing
foods, alcohol (especially red wine), dietary
chemical additives, stress, fatigue, eyestrain, etc.

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