Correspondence

Butyrolactone-Induced Central Nervous System Depression after Ingestion of RenewTrient, a “Dietary Supplement”

N Engl J Med 1998; 339:847-848September 17, 1998

Article

To the Editor:

Ingestion of γ-hydroxybutyric acid, marketed as a “body-building supplement,” may result in coma and apnea. Its sale has recently been banned by the Food and Drug Administration (FDA), but similar alternative products continue to be marketed. After the addition of water and sodium hydroxide, γ-butyrolactone, a solvent, is converted to γ-hydroxybutyric acid. Studies suggest that γ-butyrolactone poisoning can produce a clinical picture similar to that associated with γ-hydroxybutyric acid.1

RenewTrient, described on the label as a dietary supplement that “stimulates the body's own natural production of Growth Hormone,” contains γ-butyrolactone. We report a case of central nervous system depression after the ingestion of RenewTrient.

A 36-year-old man was stopped by the police after he was seen to be driving erratically. The police found him to be lethargic, with diaphoresis and vomiting. In the emergency department, a physical examination was unremarkable except that the man appeared to be inebriated. His vital signs were normal. His mental status returned to normal within one hour after his arrival at the emergency department. He reported that he had ingested, for the first time, 2 oz (59 ml) of RenewTrient approximately 30 minutes before he was placed in police custody. He stated that he had not ingested any other substances at the time.

His medical history was unremarkable. The blood ethanol level was 0, and a urinary screening test for drugs of abuse with the use of an enzyme-multiplied immunoassay technique was negative. The results of comprehensive urinary drug screening with thin-layer chromatography and gas chromatography–mass spectrometry were also negative. The urine was positive for butyrolactone, as determined by gas chromatography and flame ionization detection. The patient was well when discharged after six hours of observation. The FDA was notified.

γ-Butyrolactone, a precursor in the synthesis of γ-hydroxybutyric acid, produced an intoxication similar to that caused by γ-hydroxybutyric acid. RenewTrient contains γ-butyrolactone and as of this writing was available for purchase in health-food stores.

The label on RenewTrient states:

Higher doses will result in proportionally longer periods of deep sleep and sweating. Muscle spasms, vomiting, bedwetting, and diarrhea are typical reactions. Unless drugs or alcohol have been taken with RenewTrient™ the only treatment necessary is to SLEEP IT OFF! A call for help may result in uninformed emergency medical personnel using expensive, unnecessary and potentially dangerous methods of arousal.

This information is followed by the statement, “Use only under the direction of an orthomolecular physician.”

Frank LoVecchio, D.O.
Maricopa Medical Center, Phoenix, AZ 85006

Steve C. Curry, M.D.
Good Samaritan Regional Medical Center, Phoenix, AZ 85006

Teri Bagnasco, M.D.
Scottsdale North Memorial Hospital, Scottsdale, AZ 85251

1 References

1. 1

   Rambourg-Schepens MO, Buffet M, Durak C, Mathieu-Nolf M. Gamma butyrolactone poisoning and its similarities to gamma hydroxybutyric acid: two case reports. Vet Hum Toxicol 1997;39:234-235
   Medline

Author/Editor Response

A spokesperson for RenewTrient Research replies:

To the Editor: LoVecchio et al. quoted out of context only part of an older version of the RenewTrient label. The label now reads:

The man described by LoVecchio et al. ignored the instructions on the label, yet was discharged after six hours without treatment, which is consistent with the information on the label. We wonder whether similar reports involving any other over-the-counter sleep aids would warrant publication in the Journal.

LoVecchio et al. use misleading and inaccurate terminology. “Poisoning” suggests that the causative agent is a poison and that the patient is in imminent danger. Many over-the-counter sleep medications are indeed poisons (and hence are used in suicides), but neither γ-hydroxybutyric acid nor RenewTrient is. The insert for Gamma-OH (γ-hydroxybutyric acid as it is marketed in Europe) lists the median lethal dose as 4.28 g per kilogram of body weight, or more than half a pound for a person of average weight.

Research shows safe clinical use at levels of 40 to 80 g per day.1 This also applies to γ-butyrolactone, since γ-hydroxybutyric acid is converted to γ-butyrolactone by stomach acid (a fact confirmed by any chemistry textbook). “Coma” and “apnea” both suggest imminent danger due to hypometabolism, not normal sleep.2 Published research demonstrates that γ-hydroxybutyric acid and γ-butyrolactone do not cause hypometabolism but are treatments for it.3 It would be inappropriate to maintain that patients with narcolepsy or sleep apnea who are treated with γ-hydroxybutyric acid or γ-butyrolactone are thereby put into nightly comas, even if they may be unarousable. It should be noted that the effects of γ-hydroxybutyric acid and γ-butyrolactone are quickly reversed by the administration of 2 mg of physostigmine.4

Both γ-hydroxybutyric acid and γ-butyrolactone are nutrients that are always present in our bodies and occur in many foods.5 Their benefits and applications are well described in the literature. We have been deluged with positive responses from physicians, and we welcome correspondence.

C. Gorton
RenewTrient Research, Cocoa Beach, FL 32931

5 References

1. 1

   Entholzner E, Mielke L, Pichlmeier R, Weber F, Schneck H. EEG changes during sedation with gamma-hydroxybutyric acid. Anaesthesist 1995;44:345-350
   CrossRef | Web of Science | Medline

2. 2

   Yamada Y, Yamamoto J, Fujiki A, Hishikawa Y, Kaneko Z. Effect of butyrolactone and gamma-hydroxybutyrate on the EEG and sleep cycle in man. Electroencephalogr Clin Neurophysiol 1967;22:558-562
   CrossRef | Medline

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   Artru AA, Steen PA, Michenfelder JD. γ-Hydroxybutyrate: cerebral metabolic, vascular, and protective effects. J Neurochem 1980;35:1114-1119
   CrossRef | Web of Science | Medline

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   Henderson RS, Holmes CM. Reversal of the anaesthetic action of sodium gamma-hydroxybutyrate. Anaesth Intensive Care 1976;4:351-354
   Medline

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   Laborit H. Sodium 4-hydroxybutyrate. Int J Neuropharmacol 1964;3:433-452
   CrossRef | Medline

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