LINUS PAULING INSTITUTE RESEARCH REPORT
Why Apples are Healthful
Silvina Lotito, Ph.D.
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.
updated November 2004
Micronutrient Research for Optimum Health
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