participated in a 14-day, double-blind, placebo-controlled, crossover study with 7 days of PB treatment (30 mg three times a day and 7 days of placebo), during which exercise and cold testing were performed on days 2 and 3 and again on days 6 and 7. PB and control treatments resulted in similar metabolic rates, body temperatures, and regional heat concentrations. No differences were noted between earlier and later measurements with regard to any of the thermoregulatory and metabolic parameters. It was concluded that the study showed no “acute or chronic” effects of PB treatment on thermoregulation and metabolism during exercise in cold air.
In summary, review of studies of the effects of PB on healthy male volunteers are in general agreement with the conclusion that PB (at doses similar to those taken by troops during the Gulf War) results in no clinically significant perturbation of thermoregulatory homeostasis.
It should be noted, however, that some physiological parameters in some of the studies showed statistically significant differences for PB treatment compared to placebo. These PB-related findings include the following: mild, asymptomatic decrease in heart rate among heat- and exercise-stressed subjects (Epstein et al., 1990a); increase in nonevaporative heat exchange during heat stress with CW-protective clothing (Epstein et al., 1990b); increased sweating, increased evaporative water loss, and lowered skin temperature with dry heat stress and exertion, with an increased change in exercise-induced sweating and drop in skin temperature and heart rate on later days of treatment (Wenger et al., 1993); and episodes of self-limited but severe abdominal cramping in cold-exposed subjects (Prusaczyk and Sawka, 1991). These findings are of unknown clinical significance, but because of the rapid return to baseline, these PB-associated changes are not likely to be harbingers of long-term effects.
It is also important to notice that of the five studies (36 subjects) in which average weight and body surface area are stated,8 the measurements are similar to those expected for an average healthy male (the standard “70-kg man”). Smaller men and most women are substantially different from these subjects with regard to weight and body surface area (e.g., an average fit young American woman weighs approximately 55–65 kg and has a body surface area of about 1.5–1.75 m2). Since CW preexposure PB dosages are fixed (30 mg every 8 hours), the experimental findings in these studies could underestimate drug effects on many personnel.
Finally, these studies are limited by the small numbers of subjects and high degree of fitness among participants. Further, none of the studies were chronic in duration, nor did any study report long-term follow-up of experimental subjects. Hence, delayed effects of PB on thermoregulation, although unlikely, require further study.