The effect of vitamin E and vitamin C on 3-year progression of carotid atherosclerosis: The antioxidant supplementation in atherosclerosis prevention (ASAP) study

Salonen, J. T.; Nyyssönen, Kristiina; Salonen, Riitta; Lakka, Hanna‐Maaria; Kaikkonen, Jari; Porkkala, E.; Voutilainen, Sari; Lakka, Timo A.; Rissanen, Tiina H.; Leskinen, Leena A.; Tuomainen, Tomi Pekka; Valkonen, Veli-Pekka; Ristonmaa, Ulla; Poulsen, Henrik Enghusen

doi:10.1016/s0021-9150(00)80112-4

Cited by 54 publications

(74 citation statements)

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“…Indeed, antioxidant supplementation in various animal models has shown both positive 3,4 and negative 3,5-8 results. Similarly, the effectiveness of antioxidant supplementation is also equivocal in human studies with a number of large human trials reporting either positive outcomes [9][10][11][12] or no effect. [13][14][15][16] At present, it appears likely that the focus of future studies will be directed towards using novel combinations of antioxidants at concentrations known to provide optimal antioxidant effects both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a non-antioxidant, dose-dependent role of α -lipoic acid in caspase-3 and ERK2 activation in endothelial cells

et al. 2005

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Endothelial cell apoptosis contributes to atherosclerosis and may be exacerbated by oxidative stress. Results from clinical trials using antioxidant supplementation are equivocal and could be enhanced by antioxidants with additional non-antioxidant properties such as alpha -lipoic acid and alpha -tocopherol. The aim of this study was to investigate the effects of these antioxidants on cytoprotective pathways and endothelial apoptosis. Endothelial cells were incubated with alpha -lipoic acid and alpha -tocopherol, alone or in combination, prior to incubation with H(2)O(2) or staurosporine. alpha -lipoic acid pre-treatment alone increased caspase-3 activity in a dose-dependent manner. Both H(2)O(2) and staurosporine increased DNA fragmentation and caspase-3 activity and pre-treatment of cells with alpha -lipoic acid and/or alpha -tocopherol failed to prevent stress-induced apoptosis. Neither antioxidant treatments nor apoptotic inducers alone altered expressions of Bcl-2, Bax, HSP70 or pERK1/2 or pJNK. alpha -lipoic decreased pERK2 in staurosporine-treated cells in a dose-dependent manner. These findings indicate that pre-incubation with alpha -lipoic acid and alpha -tocopherol, alone or in combination, does not protect against oxidative- or non-oxidative-induced apoptosis in endothelial cells. Moreover, we have demonstrated a non-antioxidant, dose-dependent role of alpha -lipoic acid in caspase-3 and ERK2 activation. These data provide an insight and indicate caution in the use of high doses of alpha -lipoic acid as an antioxidant.

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Section: Introductionmentioning

confidence: 99%

Evidence for a non-antioxidant, dose-dependent role of α -lipoic acid in caspase-3 and ERK2 activation in endothelial cells

et al. 2005

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“…A number of antioxidant vitamin trials including: Cambridge Heart Antioxidant Study (CHAOS), Antioxidant [132][133][134][135] demonstrate clinical benefits in CVD. However, these are often disregarded due to the large weight of evidence against the utility of antioxidants therapy in most large-scale trials.…”

Section: Reappraisal Of Antioxidants Use: Is There Emerging Evidence mentioning

confidence: 99%

“…Another successful randomised placebo controlled antioxidant trial is the ASAP study [133]. This trial investigated combined antioxidant supplementation, over 6 years, on carotid-artery intima-media thickness (CAIMT), using ultrasonography in 520 subjects with hypercholesterolaemia.…”

Section: Reappraisal Of Antioxidants Use: Is There Emerging Evidence mentioning

confidence: 99%

“…This is significant since F 2 -isoprostanes yield valuable information on antioxidant vitamin inhibition of lipid peroxidation, testing the 'oxidative modification hypothesis.' The ASAP trial, combining vitamin C and E use, significantly reduced F 2 -isoprostanes in men [133], signifying that F 2 -isoprostanes and other surrogate markers may be valuable in assessing cardiovascular risk in specific patient populations [141]. In particular, these markers could establish pre-and post-treatment oxidant stress levels and target patients most susceptible to 'antioxidant' treatment and delineate efficacious treatment regimens.…”

Section: Reappraisal Of Antioxidants Use: Is There Emerging Evidence mentioning

confidence: 99%

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Atherosclerosis and Oxidant Stress: The End of the Road for Antioxidant Vitamin Treatment?

Thomson

Püntmann

Kaski

2007

Cardiovasc Drugs Ther

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Extensive experimental data have revealed a central role for oxidative stress in atherogenesis and suggested a potential role for 'antioxidant' treatment in cardiovascular disease (CVD) [1-11]. Experimental data, however, have not translated into clinical benefit: most antioxidant vitamin trials have failed to reduce cardiovascular morbidity and mortality [12]. Moreover, recent clinical trials have suggested that mono-therapy with certain antioxidant vitamins like vitamin E may, in fact, be detrimental [13]. As a result of the disappointing outcome of 'antioxidant' vitamin trials, some authors have questioned both the utility of 'antioxidant' treatment in CVD and the supposedly central role of oxidative stress in atherogenesis [14-19]. Other investigators, however, sustain that the beneficial effects of lipid lowering and anti-hypertensive treatment are at least, in part, due to their 'antioxidant' properties, in addition to their specific pharmacological properties [20, 21]. Oxidant stress plays a pivotal role in atherogenesis, however, the clinical promise of antioxidant vitamins has failed to translate into clinical benefit. Increasing evidence suggests that more rigorous clinical trial designs are necessary to effectively divulge antioxidant utility and that a multifaceted antioxidant approach to atherosclerosis may yield the most clinical reward. This article reviews currently available evidence on the role of oxidant stress in atherosclerosis, analyzes the results of large anti-oxidant trials, and suggests ways to investigate the true role of antioxidant treatment in the clinical setting.

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“…This intervention did not reduce total mortality and cerebrovascular disease. Recently, Salonen et al [38] studied a subgroup of 520 male smokers and nonsmokers and postmenopausal women aged 45 to 69 followed for 3 years; they reported an attenuation in carotid atherosclerosis progression only in male smokers with the combination of vitamins C and E [38].…”

Section: Randomized Trialsmentioning

confidence: 99%

Beta-carotene, vitamin C, and vitamin E and cardiovascular diseases

2000

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Observational studies have shown an inverse relationship between consumption of fruits and vegetables high in beta-carotene, vitamins C and E, and ischemic heart disease (IHD) and stroke. In large observational studies, beta- carotene reduced the risk of IHD events in men, particularly in smokers. In contrast, four large randomized trials did not reveal a reduction in cardiovascular events with beta-carotene use, and may, in fact, increase IHD and total mortality in male smokers. There have been only a few large observational studies and one randomized trial with vitamin C, which have shown no beneficial or deleterious impact of this vitamin on cardiovascular events. Most large observational studies have shown an inverse relationship between vitamin E and IHD. However, a meta-analysis of the four randomized trials done in Europe and America involving a total of 51,000 participants allocated to vitamin E or placebo for 1.4 to 6 years, did not demonstrate a reduction in cardiovascular and IHD mortality and nonfatal myocardial infarction. Currently, there are no data to support the use of these vitamins to reduce the risk of cardiovascular events. Trials are in progress to determine whether a longer duration of administration of vitamin E or the association of vitamin E with cofactors may reduce cardiovascular events.

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The effect of vitamin E and vitamin C on 3-year progression of carotid atherosclerosis: The antioxidant supplementation in atherosclerosis prevention (ASAP) study

Cited by 54 publications

References 0 publications

Evidence for a non-antioxidant, dose-dependent role of α -lipoic acid in caspase-3 and ERK2 activation in endothelial cells

Evidence for a non-antioxidant, dose-dependent role of α -lipoic acid in caspase-3 and ERK2 activation in endothelial cells

Atherosclerosis and Oxidant Stress: The End of the Road for Antioxidant Vitamin Treatment?

Beta-carotene, vitamin C, and vitamin E and cardiovascular diseases

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