Title: Alternative Sweeteners

80 Bopp and Price
0.42 µg/ml and were correlated with the urinary cyclohexylamine levels (80). In
the other study, the blood pressure and heart rate of 20 subjects were monitored
three times a day during a 10-day dosing period with sodium cyclamate (81).
Half of these subjects did not convert cyclamate to cyclohexylamine, five were
low converters, and the other five were high converters. However, no significant
changes in blood pressure or heart rate were seen, even in the high converters.
Furthermore, noninvasive hemodynamic studies, which were conducted in six
subjects known to be good converters, failed to reveal any changes that were
attributable to cyclamate or cyclohexylamine, even though the cyclohexylamine
levels in serum ranged from about 0.2–0.6 µg/ml in most subjects and reached
1 µg/ml in one subject (81).
Buss et al. (82) conducted a controlled clinical study investigating the conversion
of cyclamate to cyclohexylamine and its possible cardiovascular consequences
in 194 diabetic patients who were given calcium cyclamate (1 g/day as
cyclamic acid equivalents) for 7 days. The incidence and extent of cyclohexylamine
formation in this group of subjects were similar to those reported in the earlier
studies; 78% of subjects excreted 0.1% of the daily dose as cyclohexylamine
in urine, but 4% (8 subjects) excreted more than 20% of the daily dose as cyclohexylamine.
Similar intersubject variability was observed in the cyclohexylamine
concentrations in plasma, with concentrations of 0–0.01 µg/ml in 168 subjects,
0.01–0.3 µg/ml in 18 subjects, 0.3–1.0 µg/ml in 6 subjects, and 1.0 µg/ml in
2 subjects. A significant correlation was found between the cyclohexylamine
in plasma and urine. The changes in mean arterial blood pressure and heart rate in
the eight subjects with plasma cyclohexylamine concentrations between 0.3 and
1.9 µg/ml were similar to those found in 150 subjects with very low (0.01 µg/
ml) cyclohexylamine concentrations. In a second study conducted 10–24 months
later, 20 of the subjects were given calcium cyclamate for 2 weeks at a dose of
2 g cyclamic acid equivalents/day (0.66 g tid). Cyclohexylamine concentrations
in plasma, blood pressure, and heart rate were measured every 30 minutes during
the final 8-hr dosing interval. Twelve of the subjects had plasma cyclohexylamine
concentrations of 0.09–2.0 µg/ml at the start of the dose interval. Transient
increases or decreases in the cyclohexylamine concentrations were not observed
during the 8-hr dosing interval nor were there any significant changes in
blood pressure or heart rate measurements. Collectively, these results indicate
that the metabolism of cyclamate (2 g/day) to cyclohexylamine does not significantly
affect blood pressure or heart rate, even in those few individuals who are
high converters and have relatively high concentrations of cyclohexylamine in
plasma.
The lack of cardiovascular effects in the subjects who had plasma cyclohexylamine
concentrations of 0.3–1.9 µg/ml in the study by Buss et al. contrasts
with the observation by Eichelbaum et al. that cyclohexylamine concentrations
of 0.7–0.8 µg/ml were sufficient to increase the blood pressure of subjects given