Vitamin C pharmacokinetics of plain and slow
release formulations in smokers
Michael Viscovicha, Jens Lykkesfeldtb, Henrik E. Poulsena,*
aDepartment of Clinical Pharmacology Q 7642, Rigshospitalet, Copenhagen University Hospital,
Blegdamsvej 9, DK-2100 Copenhagen, Denmark
bDepartment of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University,
Received 13 October 2003; accepted 17 January 2004
Summary Background & aims: Combination of the antioxidants ascorbic acid in slow
release formulation and a-tocopherol can retard the progression of atherosclerosis.
In order to determine if differences in formulation could explain some of the
different results in the intervention trials we determined selected pharmacokinetics
for two different formulations of ascorbic acid together with a-tocopherol.
Methods: Single-blinded, randomised, placebo-controlled intervention study with
48 healthy men, aged 20–65 years, smoking X5 cigarettes/day. Subjects received
250mg plain release ascorbic acid and 91mg plain release d-a-tocopheryl acetate,
250mg slow release ascorbic acid and 91mg plain release d-a-tocopheryl acetate or
placebo twice daily for 4 weeks. A series of blood samples were collected after
administration of the first dose and repeated after 4 weeks of supplementation.
Results: The fluctuation of ascorbic acid plasma concentrations decreased
significantly (P ¼ 0:003) after 4 weeks supplementation in the slow versus the plain
Conclusions: This study shows that there were pharmacokinetic differences
between plain and slow release formulations of ascorbic acid. However, these
effects are small and unlikely to be of significant clinical importance.
& 2004 Elsevier Ltd. All rights reserved.
Vitamin C, or ascorbic acid, cannot be synthesised
by the human body.1Man therefore depends on
dietary intake to maintain vital biological functions
dependent on ascorbic acid. While it is well
accepted that ascorbic acid intake in doses of
about 20–90mg per day are sufficient to prevent
scurvy,2,3considerable controversy exists about the
effects of so-called mega doses, i.e. ‘‘gram’’ doses,
on the major diseases in the western society:
Cancer and atherosclerosis. A few small focused
trials4–6and larger preventive trials7of up to a few
years duration have shown benefits from antiox-
idant supplementation, e.g. reduction of the
atherosclerotic progression. These positive findings
from intervention studies are at variance with
larger and longer preventive trials where it was not
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*Corresponding author. Tel.: þ45-3545-7671; fax: þ45-3545-
E-mail address: firstname.lastname@example.org (H.E. Poulsen).
S0261-5614/$-see front matter & 2004 Elsevier Ltd. All rights reserved.
Clinical Nutrition (2004) 23, 1043–1050
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