Fructose and Uric Acid

Most of us know that uric acid serves an important purpose – it acts as the body's primary anti-oxident (neutralizer of free-radicals).

I came across the following URL today that made me wonder if we gouties are focusing too much on foods that have high levels of purines (e.g. beef, beer and shellfish) and not enough on the other things in our life that cause uric acid to rise…namely stuff like fructose.

Please take a minute to read this and let me know what you think (while this person champions the benefits of fructose, I see a direct application to our problem…)

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Copied from http://lpi.oregonstate.edu/fw04/apples.html (all bolding mine)

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Summary: Apples and other fruit are
considered to be healthy, in part due to the antioxidant flavonoids they
contain. However, these flavonoids are poorly absorbed into the bloodstream. We
found that the consumption of apples by volunteers resulted in a large increase
in the antioxidant capacity of their plasma, indicating that something other
than flavonoids may be responsible. Our further investigations showed that
fructose, a fruit sugar, in apples stimulated the production of uric acid in the
body, which provided the plasma antioxidant capacity.

Regular consumption
of fruits and vegetables lowers the risk of cardiovascular diseases, certain
types of cancer, and other chronic diseases. These beneficial effects of fruits
and vegetables have been partly attributed to their high content of flavonoids,
the intake of which is also inversely associated with the incidence of many
chronic diseases.

Flavonoids are
compounds that protect plants from pathogens, ultraviolet light, and other
stress and are responsible for the deep colors of flowers and fruits. Many
flavonoids are polyphenols, and their antioxidant properties are probably
related to their polyphenolic chemical structure.

The mechanisms by
which flavonoids may lower chronic disease risk, however, remain to be fully
elucidated. Most flavonoids have antioxidant properties, and extracts and juices
of fruits and vegetables exhibit substantial antioxidant capacity in the test
tube. Therefore, it is conceivable that the health benefits of flavonoid-rich
foods are related to the antioxidant protection of biological macromolecules,
such as lipids, proteins, and DNA. However, this remains controversial. Although
some studies have failed to show a short- or long-term antioxidant effect of
fruits, vegetables, or flavonoid consumption in humans, other studies have
reported positive results, especially an acute increase in the antioxidant
capacity of plasma. However, flavonoids cannot explain the observed increases in
plasma antioxidant capacity because their concentration in plasma is quite low.
Moreover, the metabolism of flavonoids may greatly affect their antioxidant
capacity. After consumption, flavonoids are poorly absorbed in humans. After
absorption, flavonoids are metabolized into glucuronides, which undergo further
chemical modifications, such as methylation or sulfation. Consequently, the
concentration of flavonoid metabolites in plasma is very low, yet the reported
increase in antioxidant capacity of plasma after flavonoid-rich foods are
consumed often greatly exceeds the increase in plasma flavonoids. This paradox
intrigued us.

Apples are one of the main sources
of flavonoids in the Western diets, providing approximately 22% of the total
phenols consumed per capita in the United States. Other dietary sources of
flavonoids are tea, wine, onions, fruit, and chocolate. An increased intake of
apples has been correlated with a decreased risk of heart disease, type 2
diabetes, and incidence of thrombotic stroke. Because we suspected that
flavonoids may be responsible for the health benefits of apples, exerting their
effects by antioxidant mechanisms, we conducted a study on apple consumption in
humans. First, we characterized the antioxidant capacity and flavonoid content
of apples. In collaboration with Dr. Ronald Wrolstad in the Department of Food
Science and Technology at Oregon State University, we extracted flavonoids from
the edible portion?flesh and skin?of different varieties of apples, including
Red Delicious, Granny Smith, and Fuji. We then measured the total phenol content
and the antioxidant capacity of these apple extracts by two assays: FRAP, ferric
reducing antioxidant potential, which determines the antioxidant capacity by the
ability to reduce iron, and ORAC, oxygen radical absorbance capacity, which
evaluates the antioxidant capacity by the ability to reduce peroxyl radicals.
Apple extracts, especially from Red Delicious, were powerful antioxidants, which
significantly correlated with the total phenol content. When added to human
plasma in the laboratory, Red Delicious apple extracts were remarkably
protective against oxidation. This effect could be clearly attributed to the
antioxidant polyphenol/flavonoid content in the apple extracts, which prevented
or delayed the oxidation of other plasma antioxidants and constituents, such as
lipids or proteins.

Subsequently, we
studied the short-term effect of apple consumption in humans by evaluating the
plasma resistance to oxidation after apple consumption. Additionally, we
measured the total plasma antioxidant capacity, as an estimation of the total
amount of antioxidants present in the plasma after apple consumption. After an
eight-hour fast, six healthy, nonsmoking volunteers (three men and three women,
average age of 36 years) consumed five whole Red Delicious apples with a total
weight of about 2.3 pounds. We collected blood samples from these subjects
before and 1, 2, 3, 4, and 6 hours after they ate the apples. For comparative
purposes, the same subjects consumed 2 plain bagels and water on a different
day, which provided a flavonoid-free control. We collected blood samples from
the subjects at the same time points.

When the plasma of
these subjects was exposed to chemical oxidation in the laboratory, no
significant increase in antioxidant protection was observed in plasma components
after apple consumption, in contrast to the in vitro results with apple
extracts. These results suggest that apple flavonoids are not absorbed in
sufficient amounts to significantly contribute to the antioxidant protection of
plasma components in the body. When we measured the total antioxidant capacity
of plasma after apple consumption, we observed a large, statistically
significant increase in plasma antioxidant capacity. This indicated that,
indeed, there were more antioxidants present in plasma after apple consumption.
The results obtained after apple consumption differed remarkably from those
obtained after bagel consumption. But if flavonoids weren?t responsible, what
was? Apples also contain vitamin C?about 10 mg per apple?that could also make an
important contribution to the plasma antioxidant capacity. However, neither
vitamin C nor flavonoids explained the increase in antioxidant capacity after
apple consumption. Surprisingly, the plasma antioxidant capacity increased
concomitantly with transient increases in plasma uric acid, which is an
important biological antioxidant.

A significantly
large and unexpected increase in plasma uric acid was observed 1-2 hours after
the subjects ate apples, and rapidly decreased to basal levels after 3 hours,
paralleling the increases in antioxidant capacity. The healthy participants in
this study had baseline levels of uric acid within the normal range, and the
consumption of apples did not increase uric acid beyond the previously
established healthy range of plasma uric acid.

The increase in
uric acid after apple consumption was a very surprising finding, since apples do
not contain uric acid or its dietary precursors, such as inosine or other
purines. So where did this uric acid come from? It has been known for over 30
years that fructose?a sugar present in large quantities in fruits?may increase
plasma uric acid. Fructose is quickly absorbed and taken up by the liver, where
it is rapidly metabolized. This rapid metabolism stimulates the production of
uric acid in the liver, which is subsequently excreted into plasma. The fructose
content of apples and other fruits is quite high. Thus, we hypothesized that the
fructose content in apples caused the transient increase in plasma uric acid?and
antioxidant capacity?after apple consumption. To prove this hypothesis, we
conducted a third experiment in which our healthy volunteers consumed a liter of
fructose-containing water, which matched the fructose content in their apples.
Our analyses indicated that the consumption of fructose closely mimicked the
effects of apple consumption on plasma antioxidant capacity and uric acid
concentrations, thus supporting our hypothesis.

Increases in plasma
uric acid after consumption of tea, coffee, wine, spinach, and strawberries have
been described in some previously published short-term studies. However, none of
the investigators could explain the reason. With our observations, we can now
offer the explanation that fruits may transiently increase plasma uric acid due
to the metabolism of fructose, and the contribution of this antioxidant to the
measured total antioxidant capacity of plasma is, indeed, much more significant
than the possible antioxidant contribution of the flavonoids.

These results lead
to another question: does this transient increase in uric acid after fruit
consumption represent a beneficial effect for human health? Without any doubt
the consumption of fruits and vegetables has been long associated with a lower
risk of chronic diseases and much better quality of life. Uric acid is an
important physiological antioxidant, normally present in high concentrations in
plasma, but whose metabolic functions remain unclear. Excessive uric acid in
blood causes gout in susceptible individuals, and it has been suggested that
high levels of uric acid may be linked to cardiovascular diseases. Additionally,
the long-term consumption of excessive fructose in the diet from manufactured
foods and beverages has been correlated with chronic diseases like hypertension,
hyperlipidemia, and type 2 diabetes. However, consumption of fructose in fruit
has not been shown to be harmful in healthy individuals, and several health
benefits have recently been described for uric acid, especially its possible
protection against multiple sclerosis and other inflammatory
conditions.

Based on our data,
it is conceivable that the presumed antioxidant role of flavonoids in plasma
after fruit consumption reported in numerous previous studies may have been
confounded by uric acid. The potential, specific beneficial effect of these
transient increases in uric acid after fruit consumption remains uncertain but
deserves further investigation. On the other hand, we continue to explore the
mechanism by which low concentrations of flavonoids and their metabolites may
exert health benefits. Clearly, our apple study has demonstrated that the
consumption of fruit may have a greater impact on human health and potential
health benefits for more reasons than we expected.

Last
updated November 2004