lipoprotein metabolism [7,8]. Pantethine has a mild antiplatelet
aggregation property [9] that can also modify the
membrane fluidity of cells and platelets. These multiple
mechanisms of action can contribute to the effects of
pantethine in decreasing CVD risk. A prior published
randomized, placebo-controlled, multicenter trial in Japan
of 201 high–CVD-risk individuals demonstrated that 600
mg/d (given orally in 3 divided doses over 16 weeks) of
pantethine lowered LDL-C by 15%, lowered TG by 14%,
and raised HDL-C by 17% from baseline [10].
A similar well-controlled trial of pantethine and its effect
on blood cholesterol and other lipometabolic factors has not
been previously performed on low– to moderate–CVD-risk
Western North American subjects. It has also not been
established that higher doses of pantethine above 600 mg/d
would provide incremental or proportional changes in serum
lipid levels. Pantethine is regarded as a well-tolerated agent
as described in the survey results of its clinical trials with a
median pantethine dosage of 900 mg/d to be 1.4 adverse
reactions per 100 subjects, most of which being classified as
gastrointestinal complaints of mild severity [11]. A more
recent review on the medical aspects on pantethine states that
the frequency of its side effects is very low and mild [12].
Oral pantethine has been shown to be safe and effective, and
an identical prescription product (Pantosin, a proprietary
formulation of highly absorbable and biologically active
pantethine) has been used in Japan for more than 30 years.
Oral pantethine is considered a nutritional supplement in the
United States (Pantesin, a proprietary formulation of highly
absorbable and biologically active pantethine for North
Americans) and is considered grandfathered for safe, overthe-
counter use. Based on these facts regarding the efficacy
of pantethine in high–CVD-risk subjects and its good
tolerability, we hypothesized that pantethine would improve
cholesterol metabolism in North American subjects with low
CVD risk and also causes no serious adverse events (AEs) in
these subjects. More specifically, our objective to test this
hypothesis was to clarify the benefit of oral pantethine for
subjects who are clinically less serious in terms of CVD risk
but, instead, need to have particular awareness and practices
for proper diets, dietary supplementation, and exercise rather
than taking nonnaturally occurring potent medicines that are
mainly prescribed for high–CVD-risk patients.
The purpose of this investigation was to determine the
effect of 2 dosing schedules of pantethine vs placebo on
blood cholesterol values over a 16-week treatment period for
North American subjects in ATP III CVD risk groups 1 and 2
(initially nonstatin candidates) immediately following a
4-week TLC diet lead-in.