To our knowledge, this is the first reported placebocontrolled
and diet-controlled investigation into the potential
lipid altering abilities of oral pantethine in North American
subjects. The purpose of the TLC diet lead-in phase was to
“level the playing field” so that we could eliminate or
minimize any concerns of dietary influences on our results
between the 2 treatment groups.
The results of our study confirmed the hypothesis that
pantethine lowers TC and low-density lipoprotein in low–
CVD-risk subjects in North America with statistical
significance. The comparison of our study results with
other results reported on high–CVD-risk subjects may not be
discussed precisely because of the inconsistent results and
study designs including dosages in those small-scale studies.
The primary conclusion of this investigation in low– to
moderate–CVD-risk subjects is, over and above a TLC
diet, that pantethine produced a significant decrease in TC,
LDL-C, TC/HDL ratio, non-HDL, and Apo-B documented
at week 2 after randomization that was sustained
throughout the 16-week study period. The increase from
600 mg/d in weeks 1 to 8 to 900 mg/d from weeks 9 to 16
did not appear to provide any additional or measurable
benefit with respect to lipid parameters. This would suggest
that the optimal benefit in low- to moderate-risk subjects is
achieved at a 300-mg twice-per-day dosing schedule. The
“drift” from the maximum pantethine benefit at week 2 of a
7% reduction in LDL-C to only 4% at week 16 is unclear;
however, the trend for this drift upward of LDL-C was noted
in both the placebo and pantethine study subjects and is likely
due to a similar (but not consistently documented) relaxing of
the TLC diet adherence with time. Alternatively, this could
represent a level of tachyphlaxis to pantethine at 600 mg/d,
and it remains uninvestigated whether this could have, with
time, been overcome by the higher doses of pantethine.
A prior investigation in Japan [10] had noted additionally
significant increases in HDL-C and significant decreases in
TG with the same pantethine dosing schedule used in the
current investigation; however, this investigation did not
observe similar magnitudes for changes in these lipid
parameters. There is no immediate biochemical explanation
for these differences, although it is noted that the baseline
HDL-C and TG values in our study subjects (since they were
already in the low- to moderate-CVD categories) were nearly
benefits of the TLC diet. A recent review of the “get with the
guidelines” database analysis of more than 136 000 individuals
admitted to hospital with coronary artery disease
showed the average admission LDL-C to be 104 ± 40 mg/dL
[20]; furthermore, the baseline LDL-C value was less than
130 mg/dL in three quarters—supporting the notion that
lowering LDL-C by any amount, regardless of perceived
“risk,” would be beneficial.
Although we confirmed in this study that pantethine
lowers TC and LDL-C in these low–CVD-risk subjects in
North America, there are several limitations of this study.
Even after 16 weeks of administration of pantethine, the
measured parameters did not plateau or reach a constant
level, which makes it difficult to predict the outcome of longterm
administration of pantethine. Pharmacokinetic data
such as blood levels of pantethine during the course of 600 or
900 mg of pantethine administration are limited in this study.
The precise understanding of the mechanisms of actions of
pantethine and the optimum dosage determination requires
further investigation.