OBJECTIVE: The binding of sweet-tasting compounds in a human (Mcg) Bence-Jones
dimer has been characterized by x-ray crystallography. Aspartame binding in this
immunoglobulin fragment is remarkable. Unexpected pain relief noted by A.B.E., a
crystallographer with diagnosed osteoarthritis, suggested that the accommodation
of aspartame in the active site of the dimer may represent surrogate binding by
other proteins, with analgesia as the outcome. METHODS: X-ray analysis of the
complex of aspartame and the Bence-Jones dimer was conducted with crystalline
Mcg protein and pure aspartame. A single-blind (n = 1) study to confirm
analgesia was completed by administration of aspartame to A.B.E. A controlled
double-blind trial was performed in patients with x-ray-documented
osteoarthritis. Pain and performance changes were evaluated with use of two
doses of placebo and two doses of aspartame. Effects on bleeding time were then
evaluated by determination of template bleeding times in 34 normal volunteers.
Finally, antipyretic effects were studied in Sprague-Dawley rats given
intramuscular turpentine injections. RESULTS: Aspartame binding in the
Bence-Jones dimer was verified by x-ray crystallography. Improvements in
performance and pain relief were observed in A.B.E. at p < 0.001. Decreased
pain and improved performance were also observed in patients with osteoarthritis
(p < 0.001). Mild antihemostatic responses were observed in bleeding times
after aspartame treatment. Modified template bleeding times increased at p <
0.01. Aspartame blocked the turpentine-mediated febrile responses in the treated
rats (p < 0.01). CONCLUSIONS: L-Aspartyl-L-phenylalanine methyl ester is
biologically active and appears to relieve pain, induce mild antithrombotic
effects in humans, and decrease fever in animals.