Review
Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?

https://doi.org/10.1016/j.abb.2008.01.028Get rights and content

Abstract

Diets rich in polyphenols are epidemiologically associated with lower risk of developing some age-related diseases in humans. This apparent disease-protective effect of polyphenols is often attributed to their powerful antioxidant activities, as established in vitro. However, polyphenols can also exert pro-oxidant activities under certain experimental conditions. Neither pro-oxidant nor anti-oxidant activities have yet been clearly established to occur in vivo in humans, nor are they likely given the limited levels of polyphenols that are achievable in vivo after consumption of foods and beverages rich in them. Other actions of polyphenols may be more important in vivo. Many studies of the biological effects of polyphenols in cell culture have been affected by their ability to oxidise in culture media, and awareness of this problem can avoid erroneous claims.

Section snippets

Polyphenols as antioxidants

Foods and beverages rich in flavonoids and other polyphenols have been associated with decreased risk of age-related diseases in several (but not all) epidemiological studies [9], [10], [11], [12], [13], [14], [15]. Flavonoids have powerful antioxidant activities in vitro, being able to scavenge [16], [17], [18], [19], [20], [21], [22], [23] a wide range of reactive oxygen, nitrogen, and chlorine species, such as superoxide O2-, hydroxyl radical OH, peroxyl radicals RO2, hypochlorous acid

Polyphenols as pro-oxidants

Polyphenols oxidise readily in beverages [25], [26], [27] such as green tea. They can also oxidise in cell culture media (see below) and even in the oral cavity; holding or chewing green tea in the mouth generates substantial levels of H2O2[28]. Often, these pro-oxidant effects involve interactions of polyphenols with transition metal ions [1], [29], [30], [31], [32], [33], [34], [35]. Oxidation of polyphenols produces O2-, H2O2 and a complex mixture of semiquinones and quinones, all of which

Are polyphenols pro-oxidants or antioxidants in vivo in humans?

No data are available on whether polyphenols are antioxidant or pro-oxidant in vivo in the human stomach, intestines, and colon, where they can be present at significant levels [38], [39], [46], [47]. As for effects after absorption into the body, multiple well-designed human studies have been done using reliable biomarkers of oxidative damage in plasma (F2-isoprostanes) and urine (F2-isoprostanes, isoprostane metabolites, 8-hydroxy-2′-deoxyguanosine [8OHdG]), essentially testing for systemic

Antioxidants in cell culture

Cell culture has often been used to study the cellular effects of reactive species and of antioxidants, and many useful data have resulted. However, one must be cautious, for two reasons. First, normal culture conditions are a state of hyperoxia [70], [71]. Most cells in the human body are exposed to O2 concentrations in the range of 1–10 mm Hg (obvious exceptions include corneocytes, corneal and respiratory tract lining cells). Yet culture under 95% air/5% CO2 is about 150 mm Hg of O2. Rates of

Conclusion

Polyphenols are metabolized as “typical xenobiotics” by the human body, and such metabolism decreases their antioxidant and pro-oxidant abilities. It is now looking unlikely that polyphenols act as antioxidants in vivo, and attention is turning to their other potential effects. Even so, whether polyphenols contribute to human health by any mechanism remains uncertain. Care is needed when studying their effects in cell culture to use biologically-relevant levels, to examine the effects of

Acknowledgment

I am grateful to the Biomedical Research Council of Singapore for support (BMRC 01/1/21/18/213).

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