Only a tiny portion of the gram or two of tryptophan we eat each day finds its way into the brain, where serotonergic neurons convert it to 5-HTP and then serotonin.

Thanks to well-timed supplements of tryptophan or 5-HTP, millions of people have bolstered their brain's usual supply of serotonin, relieving their depression, chronic pain and other conditions, with few or no side effects. But some users have taken a bruising -- and not just from the catastrophic eosinophilia-myalgia syndrome (EMS) wrought by tryptophan in 1989.

The Eosinophilia-Myalgia Syndrome

The eosinophilia-myalgia syndrome (EMS) afflicted thousands, killed dozens and lingers in hundreds of victims to this day. It resembles a chronic autoimmune disease, with aching joints and muscles, elevated white blood cells (eosinophils), fever, skin rash and fibrosis (hardening), swollen limbs, weakness and such long-term complications as lung disease (including pulmonary hypertension) and cognitive impairment.

Based on overwhelming evidence, there is a virtual consensus among authorities that the EMS epidemic was due not to tryptophan itself, but to contaminated lots of tryptophan from a major Japansese manufacturer, Showa Denko. Unfortunately, this was not the only time that EMS or EMS-like symptoms occured in users of tryptophan and 5-HTP. Eosinophilia, scleroderma-like lesions, and even primary pulmonary hypertension have made rare appearances before and since. In one case a Showa Denko-like impurity was found in the 5-HTP. Some experts now wonder if mild, sporadic contamination has always been a problem with tryptophan and 5-HTP and/or if these nutrients may be inherently toxic.

There are, in fact, several normal products of tryptophan metabolism that, in excess, have been implicated in certain diseases, including AIDS dementia, bladder tumors, cataracts, Parkinson's disease and scleroderma.

Serotonin itself is one such toxic metabolite. Moderate peripheral excesses account for many of the side effects of tryptophan and 5-HTP. Extreme excesses are implicated in something more serious: fibrosis in the skin (scleroderma) and in the right chamber of the heart. While there have been no reports of heart fibrosis in tryptophan and 5-HTP users, sclerodermatous lesions are rare side effects -- and common symptoms of EMS.

So the bad news is that tryptophan and 5-HTP may pose inherent dangers. The better news is that, save for the bad Showa Denko lots, in many millions of patient years of use, only a few dozen cases of drastic or life-threatening reactions have been reported. Were the statistics much worse, it is doubtful that tryptophan and 5-HTP would still be available in pharmacies in Canada (tryptophan only) and Europe, through compounding pharmacies and as investigational drugs in the United States, in the mail order catalogs of several American and foreign retailers and in the liquid meal replacements of hospital patients and infants (tryptophan only). [Note: 5-HTP is now widely available over the counter in the US and Canada.]

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