Vitamin C pharmacokinetics of plain and slow release formulations in smokers

Department of Clinical Pharmacology Q 7642, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Denmark.
Clinical Nutrition (Impact Factor: 4.48). 11/2004; 23(5):1043-50. DOI: 10.1016/j.clnu.2004.01.007
Source: PubMed


Combination of the antioxidants ascorbic acid in slow release formulation and alpha-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 alpha-tocopherol.
Single-blinded, randomised, placebo-controlled intervention study with 48 healthy men, aged 20-65 years, smoking > or = 5 cigarettes/day. Subjects received 250 mg plain release ascorbic acid and 91 mg plain release d-alpha-tocopheryl acetate, 250 mg slow release ascorbic acid and 91 mg plain release d-alpha-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.
The fluctuation of ascorbic acid plasma concentrations decreased significantly (P = 0.003) after 4 weeks supplementation in the slow versus the plain release group.
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.

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    ABSTRACT: Smoking has been identified as one of the major risk factors in human diseases such as atherosclerosis and several cancers (Doll et al. 1994; Mosca et al. 1997; Palmer 1985; Stein et al. 1993), yet approximately one third of the Western World's adult population continues to smoke (WHO Health for All Database 2000). Among other factors, oxidative stress has been suggested to play an important role as initiator of the pathological conditions resulting from tobacco smoking (Colditz et al. 1987; Frei et al. 1991; Genkinger et al. 2004; Gey 1986; Hirvonen et al. 2000; Macfarlane et al. 1995; Poulsen et al. 1998; Pryor and Stone 1993). Because cigarette smoke has been shown to result in increased oxidative stress as measured by a variety of biochemical markers, it has been speculated that increased consumption of fruits and vegetables rich in antioxidants or even specific antioxidant supplements could perhaps be particularly beneficial to smokers (Ames 1998; Ames and Gold 1998; Ames and Wakimoto 2002; Ames et al. 1995;). Indeed, numerous reports have shown that cigarette smokers have lower plasma concentrations of almost all low-molecular-weight antioxidants (Eiserich et al. 1995; Kallner et al. 1981; Lykkesfeldt et al. 1997; Munro et al. 1997). This condition results from at least two factors, one of diet and one of smoking (Dietrich et al. 2003; Lykkesfeldt et al. 1996, 2000; Schectman 1993; Schectman et al. 1991). Thus, because of the consumption of a diet containing more fat and less fruits and vegetables, smokers have a lower intake of a variety of phytonutrients, compared with nonsmokers (Dallongeville et al. 1998; Faruque et al. 1995; Jarvinen et al. 1994; Larkin et al. 1990; Ma et al. 2000; Marangon et al. 1998a; Morabia and Wynder, 1990; Preston, 1991; Serdula et al. 1996; Zondervan et al. 1996). However, in addition to dietary differences, it has been shown in studies correcting for dietary intakes of antioxidants, that in particular, vitamin C is further depleted by the smoke itself (Dietrich et al. 2003; Lykkesfeldt et al. 1996, 2000; Schectman et al. 1991). So the question remains: Should supplementation with vitamin C among smokers be a higher priority for health professionals?
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    ABSTRACT: Antioxidants are emerging as prophylactic and therapeutic agents. These are the agents, which scavenge free radicals otherwise reactive oxygen species and prevent the damage caused by them. Free radicals have been associated with pathogenesis of various disorders like cancer, diabetes, cardiovascular diseases, autoimmune diseases, neurodegenerative disorders and are implicated in aging. Several antioxidants like SOD, CAT, epigallocatechin-3-O-gallate, lycopene, ellagic acid, coenzyme Q10, indole-3-carbinol, genistein, quercetin, vitamin C and vitamin E have been found to be pharmacologically active as prophylactic and therapeutic agents for above mentioned diseases. Antioxidants are part of diet but their bioavailability through dietary supplementation depends on several factors. This major drawback of dietary agents may be due to one or many of the several factors like poor solubility, inefficient permeability, instability due to storage of food, first pass effect and GI degradation. Conventional dosage forms may not result in efficient formulation owing to their poor biopharmaceutical properties. Principles of novel drug delivery systems need to be applied to significantly improve the performance of antioxidants. Novel drug delivery systems (NDDS) would also help in delivery of these antioxidants by oral route, as this route is of prime importance when antioxidants are intended for prophylactic purpose. Implication of NDDS for the delivery of antioxidants is largely governed by physicochemical characteristics, biopharmaceutical properties and pharmacokinetic parameters of the antioxidant to be formulated. Recently, chemical modifications, coupling agents, liposomes, microparticles, nanoparticles and gel-based systems have been explored for the delivery of these difficult to deliver molecules. Results from several studies conducted across the globe are positive and provided us with new anticipation for the improvement of human healthcare.
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