Uric acid, not flavonoids increases antioxidant capacity from (apple) juice

In my article on “super”fruits I noted that many flavonoids have poor bioavailability, necessitating in vivo studies when assessing health effects- we cannot extrapolate the antioxidant capacity results of in vitro studies of flavonoid extracts to suggest that they are the reason fruits/vegetables are healthy.  This 2006 review by Lotito and Frei concluded that uric acid may be the major reason antioxidant capacity increases in the in vivo studies, consequent to the metabolism of fructose.  I also wrote about a recent study that suggests anthocyanins from cranberry juice don’t achieve a high enough concentration in human plasma to be major antioxidant contributors.

A recent study by Godycki-Cwirko et al. adds some insight to the issue.

In vitro studies have similarly shown that some apple polyphenols have strong antioxidant activities.  In most studies where subjects consume apple juice (or other juices) (even just slightly more than a half a cup) plasma antioxidant activity increases.  Recent studies have demonstrated that this may be better explained by the fructose content of apples/juice causing an increase in plasma uric acid, which has antioxidant activity, however baseline plasma polyphenols were not measured in some of these and there were other limitations.

This new study had 12 healthy subjects consume 1L of clear apple juice with defined antioxidant activity, sugar, and polyphenol content on antioxidant capacity (measured by FRAP and DPPH radical-scavenging activity (abbreviated DPPH during the rest of this post)) and measured uric acid, glucose, quercetin, and total plasma polyphenol concentrations over 4 hours post juice consumption.  The same measurements were done after ingestion of cloudy apple juice (positive control) clear apple juice with polyphenols removed, as well as water (negative control).  Each subject consumed each of the 4 drinks on different days.

The juices contained the following (note the similar sugars in each; fructose content was ~90 grams or ~a little over 4 12oz cans of soda):

In vitro experiments showed that cloudy and clear apple juice increased antioxidant activity measured by both DPPH and FRAP, and FRAP increased by the clear juice without polyphenols, as seen below, but note that its ability is not as great as the juices with polyphenols.

Serum uric acid increased with the cloudy juice, clear juice, and clear juice without polyphenols 21.4%, 11.1%, and 14.8% respectively after 1 hour then decreased to baseline within 4 hours.

Uric acid concentrations correlated strongly with FRAP and DPPH before and after each juice consumption at all time-points.

In vivo, there was no significant changes in total plasma polyphenols after consumption of any of the juices. This of course resulted in no correlations between plasma polyphenols and blood antioxidant activity.

These experiments suggest that even though polyphenols from the juice add a significant amount of antioxidant activity in vitro, the main cause for the measurement of antioxidant activity in vivo is from the increase in uric acid, as FRAP and DPPH measurements were not significantly different after the consumption of each juice.  Fructose is the only sugar that increases uric acid.

So is the increase in antioxidant activity from uric acid a good or bad thing?  Probably more likely the latter- the authors note that it has negative effects especially on the epithelial and vascular smooth muscle cells, and is associated with cardiovascular and renal disease and gout.  This is a good example of why we can’t associate “antioxidant” with good without considering context. Fructose at this amount is likely over the amount that may have negative effects on metabolic markers.  At lower amounts, it may in fact have some benefits.  Using antioxidant activity as evidence that fruit and fruit juice consumption is healthy is clearly misrepresenting the complexity of the system in different contexts (e.g. doses).  And even though uric acid is associated with certain diseases, this should not scare us away from fruit consumption, in which it would be difficult to consume the amount of fructose used in this study, and uric acid would have a dose dependent negative effect.

Existing studies on fruit and fruit juice consumption (except for 1?) have not measured uric acid, thus uric acid could explain at least part of their findings of increased antioxidant activity.

A lack of a measurement of antioxidant activity from polyphenols in vivo does not mean polyphenols are worthless.  Next week, i’ll detail an interesting paper that suggests their effects in the body are much more complex than I had imagined.


Godycki-Cwirko M, Krol M, Krol B, Zwolinska A, Kolodziejczyk K, Kasielski M, Padula G, Grębocki J, Kazimierska P, Miatkowski M, Markowski J, & Nowak D (2010). Uric acid but not apple polyphenols is responsible for the rise of plasma antioxidant activity after apple juice consumption in healthy subjects. Journal of the American College of Nutrition, 29 (4), 397-406 PMID: 21041815