Introducing: 5HTP-SeroTonic^TM

Forget Tryptophan! Forget Prozac!

DEPRESSION, ANXIETY, AND SLEEP BREAKTHROUGH

"With all due deference to scientific scepticism, the reluctance shown by some authors...to concede 5-HTP's place among acknowledged pharmacotherapeutics routinely applied against depression does not seem warranted, neither on empirical nor on theoretical grounds."

W.P. Poldinger, B. Calanchini, & W. Schwarz, authors of a 1991 review published in Psychopathology

We are living in the age of Prozac, and Zoloft, and Paxil, and other similar drugs. Originally developed to treat depression, these drugs are now also widely prescribed for such disorders as anxiety, obsessive-compulsive disorder, migraine headaches, sleep disturbances, weight loss, PMS, obesity, and back pain. Not only do we take these drugs, we also "listen" to them. In his best-selling book, Listening to Prozac, psychiatrist Peter D. Kramer, MD, has argued that taking Prozac and similar drugs may actually help some people reconfigure their personality. This has opened a broad new avenue of use by people with no obvious psychiatric illness, who just want to feel more confident, popular, mentally nimble, and emotionally resilient.1

Taking these expensive prescription drugs may not be the only way to obtain their substantial benefits, however. Prozac, as well as its chemical cousins, work by increasing the availability of the essential neurotransmitter serotonin, or 5-hydroxytryptamine (5-HT), in synapses in certain key areas of the brain by blocking their reuptake (See Fig. 1). Because of this action, they are classified as "selective serotonin reuptake inhibitors," or SSRIs.

You can also increase the availability of serotonin by taking supplements containing its metabolic precursors, the amino acids tryptophan and 5-hydroxytryptophan, (5-HTP), which increase the cell's output of serotonin (5HT).

As you can see in Figures 1 and 2, brain cells synthesize 5-HT by a two-step process that begins with tryptophan, which comes from dietary sources. Once taken up into a cell, tryptophan is converted into 5-HTP, which, in turn, is converted to 5-HT. Tryptophan supplements have a long history of use for treating depression and anxiety disorders, and for enhancing sleep. Unfortunately, since 1988, the FDA has enforced a dubious state of near-total tryptophan prohibition based on the occurrence of serious side effects caused by a single contaminated batch of the amino acid produced by a Japanese company during the late 1980s. This Japanese company had altered the time-honored manufacturing procedure for the production of tryptophan, introducing a new and untested procedure while abbreviating an important filtering step.

Such adverse effects have never been linked to any other batches of tryptophan. Nevertheless, the FDA, in its "wisdom," has maintained its prohibition in the face of overwhelming evidence that such prohibition is not only unnecessary, but may be forcing people to take dangerous and expensive drugs to achieve the benefits they could achieve safely and inexpensively with tryptophan.

The FDA's prohibition does not apply to the next step in serotonin metabolism, 5-HTP, though. And while tryptophan prohibition may be needless and deplorable, it has had one unforeseen benefit. It has allowed us to focus on 5-HTP, which, it turns out, may be even better than tryptophan ever was for treating disorders that appear to be related to a deficiency of serotonin in the brain.

The 5-HTP-Depression Connection

Various behavioral and biochemical studies have shown that 5-HTP is closely involved in depressive disorders. In a study employing positron-emission tomography (PET) scanning, eight healthy volunteers and six people diagnosed with major depression received infusions of radiolabelled 5-HTP. The researchers found that significantly less 5-HTP crossed the blood-brain barrier into the brains of the depressed subjects than into the brains of the normal controls. The authors suggested that the transport of 5-HTP across the blood-brain barrier may be compromised in major depression.2

In a French trial of 36 patients with severe depression who were treated with 5-HTP, the authors reported 28 positive results, four cases of intolerance to the treatment, and four treatment failures.3 Japanese researchers gave 5-HTP to 24 patients hospitalized for depression. After 2 weeks of treatment, they observed a "marked amelioration of depressive symptoms" in seven patients with unipolar depression. The administration of 5-HTP was also found to be associated with a 30% increase in the levels of 5-HIAA, the primary metabolite of serotonin, in the patients' cerebrospinal fluid. This suggested that the exogenous 5-HTP was being converted to serotonin.4

Double-blind clinical trials that compared the efficacy of tryptophan and 5-HTP in people with depression found 5-HTP to be clearly superior.5 A few studies have also compared 5-HTP with standard tricyclic antidepressants (eg, Elavil)--the most effective drugs for treating depression until the development of the SSRIs--and found 5-HTP to be at least as effective as these drugs in treating very severe depression, with fewer side effects.6-8

5-HTP vs SSRIs

How does 5-HTP stand up against the current standard of treatment, the SSRIs? That's the question that was asked in a double-blind, multicenter study by a team of Swiss and German psychiatric researchers headed by Dr. W. Poldinger of the Psychiatrische Universit tsklinik in Basel, Switzerland.9 The subjects, all of whom were diagnosed with depression, received either 100 mg of 5-HTP three times a day, or 150 mg of fluvoxamine (an SSRI) three times a day. The subjects were evaluated at 0, 2, 4, and 6 weeks, using standard depression rating scales. They also evaluated how they felt.

The results were startling. Both treatment groups showed a significant and nearly equal reduction in depression beginning at week 2 and continuing through week 6. After 4 weeks, 15 of the 36 patients treated with 5-HTP, and 18 of the 33 patients treated with fluvoxamine had improved by at least 50%, according to scores on the depression rating scales. By week 6, the two groups had about equal numbers showing 50% improvement (See Fig. 3). When the numbers were totaled up at the end of the study, the researchers found that the mean percentage improvement from baseline to the final assessment was actually greater for the patients treated with 5-HTP. The number of treatment failures was also higher in the fluvoxamine group (17%) than in the 5-HTP group (6%), although this difference was not statistically significant. The patients' self-assessments of how they were feeling closely paralleled the scores on the depression rating scales.

Adverse side effects from both treatments were rare and generally mild, usually occurring during the first few days of treatment and then disappearing. Overall, 5-HTP appeared to be better tolerated than the SSRI. Curiously, the Physicians' Desk Reference reports serious adverse effects for fluvoxamine in other studies, although no serious side effects could be found for 5-HTP.

Poldinger and his colleagues argue that, although 5-HTP appears to be treating depression, it may, in fact, be treating a much broader disease, which they term "serotonin deficiency syndrome." This syndrome may manifest in any of a variety of forms, including depression, anxiety, sleeplessness, aggressiveness, aggitation, obsessive-compulsive traits, migraines, and other common behavioral disorders; in short, everything that is currently being treated with SSRIs today.

"The behavioral expression (symptoms) of the dimensions related to disturbances of the serotonergic system make up a functional target syndrome, which calls for being corrected through making up for the serotonin deficiency and through inducing a down-regulation of serotonergic receptors," they write.9 If Dr. Poldinger and his colleagues are correct about their conceptualization of serotonin deficiency disorders, 5-HTP should also be effective in treating many of the same syndromes that SSRIs are currently used for. While no one has looked at this question systematically, let's see what a brief perusal of the literature shows:

Relieving Anxiety

Ten patients diagnosed with anxiety syndromes were treated with 5-HTP. A significant reduction in anxiety was observed on three different scales designed to measure anxiety.10 In a study of 20 people with panic disorders, several experienced a feeling of "relief" after receiving 5-HTP.11

Enhancing Sleep

One of the main reasons people used to take tryptophan during the pre-prohibition days was to enhance their sleep. If you look closely at Figure 2, you may see the reason why. One of serotonin's metabolic pathways leads directly to melatonin, widely acknowledged today as the hormone that helps determine our sleep-wake cycle. (See article on melatonin, Life Enhancement News, p. 7, issue 25). By increasing your production of serotonin by taking 5-HTP, you're also increasing your production of melatonin. While the role of serotonin and melatonin in sleep has been well-documented, only a few studies have looked at the connection between 5-HTP and sleep. French researchers found that 100 mg of 5-HTP resulted in significant improvement in people described as "mildly insomniac."12 Looking at sleep patterns in cats, a Norwegian scientist found that 5-HTP had effects on sleep that were similar to those produced by tryptophan.13

Suppressing Appetite

SSRIs are commonly prescribed to suppress appetite in people who want to lose weight. It appears that 5-HTP may have a similar effect. A group of Italian researchers reported that 20 obese patients taking 5-HTP (900 mg/day) lost a significant amount of weight, had less carbohydrate intake, and consistently became sated earlier than a similar group taking a placebo. They concluded that since 5-HTP was well-tolerated, it could be safely used to treat obesity.14 According to British researcher, J. Blundell, of the University of Leeds, of the many appetite suppressants found to be "active" in laboratory animals, very few have clinical potential. Among the most promising candidates, he argues, are those that increase central levels of serotonin.15

Preventing Migraine Headaches

Migraine headaches are closely associated with serotonergic activity. The most effective drugs for halting migraine attacks (eg, sumatriptan and dihydroergotamine) block specific serotonin receptors in the brain. SSRIs have also been effective in some people in preventing migraines. A few studies have found that 5-HTP may also be able to prevent migraines. Spanish researchers gave 5-HTP or methysergide, a long-time migraine treatment, to 124 migraineurs. They noted significant improvement in 71% of the 5-HTP-treated people and 75% of the methysergide-treated people. Among those treated with 5-HTP, improvement took the form of reduced intensity and duration, while frequency remained unchanged, and 5-HTP caused far fewer side effects than methysergide. The authors suggested that 5-HTP could be a treatment of choice in migraine prophylaxis.16

A group of Italian researchers confirmed the prophylactic effect of 5-HTP in 40 patients with migraine in a double-blind study. The patients were randomized to receive either 5-HTP (400 mg/day) or placebo for 2 months. By the end of 2 months, more than 90% of the 5-HTP-treated patients responded with a reduction in headache severity, frequency and duration, compared with only 16% of the placebo-treated patients.17

Listening to 5-HTP

"In functional dimensional parlance, treating a serotonin deficiency is tantamount to treating all symptoms figuring as behavioral expressions of the serotonin-dependent psychological dysfunctions," write Poldinger, Calanchini, and Schwarz.9 They point out that these symptoms of serotonin deficiency may include depression, anxiety, sleep disorders, obsessive-compulsive traits, and other psychological disorders. They also argue that the best way to address this deficiency may not be through SSRIs and other powerful, expensive, and in some cases, dangerous drugs. Rather, the answer may lie in a precursor to serotonin, 5-HTP, which has been neglected by many scientists despite tantalizing hints in the scientific literature that it may have profound effects on a variety of extremely common and often debilitating ailments. Perhaps we should be listening.

References

1. Kramer PD. Listening to Prozac. New York: Viking; 1993.
2. Agren H, Reibring L, Hartvig P, et al. Low brain uptake of L-(11C)5-hydroxytryptophan in major depression: A positron emission tomography study on patients and healthy volunteers. Acta Psychiatr Scand. 1991;83:449-455.
3. Laboucarie J, Rascol A, Guiraud-Chaumeil B, El-Hage W. La place du 5-hydroxytryptophane levogyre dans les etats depressifs. Rev Med. 1977;13:519-524.
4. Takahashi S, Kondo H, Kato N. Effect of L-5-hydroxytryptophan on brain monoamine metabolism and evaluation of its clinical effect in depressed patients. J Psychiat Res. 1975;12:177-187.
5. van Praag HM, Lemus C. Monamine precursors in the treatment of psychiatric disorders. In: Wurtman R, Wurtman J, eds. Food Constituents Affecting Normal and Abnormal Behavior: Nutrition and the Brain. New York: Raven Press; 1986:80-138.
6. van Praag HM, Van Den Burg W, Bos ERH, Dols LCA. 5-hydroxytryptophan in combination with clomipramine in "therapy-resistant" depression. Psychopharmacology. 1974;38:267-269.
7. Nardini M, DeStefano R, Ianuccelli M, Borghesi R, Battistini N. Treatment of depression with l-5-hydroxytryptophan combined with chlorimipramine: A double-blind study. J Clin Pharmacol Res. 1983;3:239-250.
8. Angst J, Woggon B, Schoopf J. The treatment of depression with l-5-hydroxytryptophan versus imipramine: Results of two open and one double-blind study. Arch Psychiatr Nervenkr. 1977;224:175-186.
9. Poldinger 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.
10. Kahn RS, Westenberg HGM. L-5-Hydroxytryptophan in the treatment of anxiety disorders. J Affect Disord. 1985;8:197-200.
11. Den Boer JA, Westenberg HGM. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res. 1990;31:267-278.
12. Soulairac A, Lambinet H. Action du 5-hydroxytryptophane, precurseur de la serotonine, sur les troubles du sommeil. Ann Med-Psychol. 1977;135:792-798.
13. Ursin R. The effect of 5-hydroxytryptophan and l-tryptophan on wakefulness and sleep patterns in the cat. Brain Res. 1976;106:106-115.
14. Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese subjects treated with 5-hydroxytryptophan. Am J Clin Nutr. 1992;56:863-868.
15. Blundell J. Pharmacological approaches to appetite suppression. Trends Pharmacol. 1991;12:147-157.
16. Titus F, Davalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol. 1986;25:327-329.
17. De Benedittis G, Massei R. 5-HT precursors in migraine prophylaxis: A double-blind cross-over study with L-5-hydroxytryptophan versus placebo. Clin J Pain. 1986;3:123-129.