Following the recent discussions about abuse of gamma-hydroxybutyric acid
(GHB) - the following caught my eye. Having (for once) managed to read
this week's New England Journal of Medicine on time, this letter may be of
interest (along with teh manufacturer's somewhat fishy reply!)

If you want to see it with formatting look at:

http://www.nejm.org/content/1998/0339/0012/0847b.asp

Otherwise it follows below. Incidentally, the latest issue has a rather
thought provoking article on "alternative therapy".

Neil

.................................................................
Neil Iosson			Tel/Fax: (01223) 569015
Gonville & Caius College        E-mail:  [log in to unmask]
CAMBRIDGE, UK

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



          To the Editor:

          Ingestion of (gamma)-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, (gamma)-butyrolactone, a
solvent, is converted to (gamma)-hydroxybutyric acid. Studies
          suggest that (gamma)-butyrolactone poisoning can produce a
clinical picture similar to that associated with (gamma)-hydroxybutyric
          acid. (1)

          RenewTrient, described on the label as a dietary supplement that
"stimulates the body's own natural production of Growth Hormone,"
          contains (gamma)-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.

          (gamma)-Butyrolactone, a precursor in the synthesis of
(gamma)-hydroxybutyric acid, produced an intoxication similar to that
caused
          by (gamma)-hydroxybutyric acid. RenewTrient contains
(gamma)-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(trademark) 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

          References

          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;39:234-5.
          Return to Text


     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:

               WARNING: A dose of one ounce will induce stage 3 and 4
(deep) sleep in most people (except those who are clinically
               depressed) within 30 minutes. Sleep normally lasts 3 to 6
hours. Use ONLY when sleep is safe and desired. Ensure that those
               around you are aware that you may be unarousable and that
this is normal. Higher doses will result in proportionally longer
               periods of deep sleep. Excessive doses may result in
sweating, muscle spasms, vomiting, bedwetting, and diarrhea. Unless drugs
               or alcohol have been taken with RenewTrient(trademark) 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.

          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
          (gamma)-hydroxybutyric acid nor RenewTrient is. The insert for
Gamma-OH ((gamma)-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 (gamma)-butyrolactone, since
          (gamma)-hydroxybutyric acid is converted to
(gamma)-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
          (gamma)-hydroxybutyric acid and (gamma)-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 (gamma)-hydroxybutyric acid or
          (gamma)-butyrolactone are thereby put into nightly comas, even
if they may be unarousable. It should be noted that the effects of
          (gamma)-hydroxybutyric acid and (gamma)-butyrolactone are
quickly reversed by the administration of 2 mg of physostigmine. (4)

          Both (gamma)-hydroxybutyric acid and (gamma)-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




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