1a. Objectives (from AD-416):
1. Identify and quantify the phytochemical content of: blueberries, cranberries, and grapes; almonds, pistachios, and walnuts; whole grains; and cocoa-based foods and contribute to future updates of the USDA Database for the Flavonoid Content of Selected Foods. 2.Determine the bioavailability, pharmacokinetics, metabolism and bioactivity of flavonoids and other phytochemicals from antioxidant-rich foods using in vitro experiments, animal models, and human studies. 3. Investigate the effect of age on quercetin bioavailability and metabolism due to changes in phase II enzyme activity. 4. Test whether exposure of rat dams to a “Western” diet during pregnancy and lactation will increase obese phenotypes in their pups and whether dietary flavonoids, particularly isoflavones, will decrease the obese phenotype.
1b. Approach (from AD-416):
Using advanced chromatographic methods, we will measure the flavonoid content and evaluate the total antioxidant capacity of selected plant foods and the influence of geographical regions, agricultural practices, and processing and storage. A rat model as well as microsomes from various rat tissues will be utilized to determine the effect of age on quercetin bioavailability and metabolism due to changes in phase II enzyme activity. We will explore the possible fetal origins of chronic disease by feeding obesigenic diets to rat dams during pregnancy and lactation and examine the change in obese phenotypes in their pups and test whether dietary flavonoids, particularly isoflavones, will decrease this phenotype. Using healthy older adults, we will determine the bioavailability and distribution of cranberry anthocyanins to blood, urine, and feces. Employing volunteers with coronary heart disease, we will test the effect of almond consumption on biomarkers of oxidative stress, inflammation, and vascular reactivity.
3. Progress Report:
Walnuts may improve the function of blood vessels in part by reducing the action of damaging oxidative reactions. However, which components of the walnut (and thus, which nutrient constituents) provide this benefit is not known. We conducted a clinical study to evaluate the effect of consuming walnut skins, de-fatted nutmeat, and nut oil as well as whole walnuts in overweight and obese adults with moderately high serum cholesterol. Walnut oil improved the responsiveness of blood vessels to stress compared to walnut skins, and these changes were associated with improvement in the transport of cholesterol out of cells. However, these changes were not associated with differences in selected biomarkers of oxidative stress. This work helps substantiate the FDA health claim regarding the benefits of tree nuts on heart health. Avenanthramides (AV) are a class of plant chemicals with antioxidant and anti-inflammatory properties that appear unique to oats. We examined the absorption of AV from the bran of oats subjected to “false malting,” a process that enriches the AV content of native kernels up to 40-fold, in a clinical trial of healthy older adults. Blood samples were collected before and after a single consumption of muffins prepared with this bran and tested for the presence of six different forms of AV. We found AV from false malted oats were absorbed into plasma within 1 to 2 hours with the concentration of different forms of AV compounds varying up to 25-fold. The pattern of absorption suggested that some AV are excreted from the liver back into the small intestine where they are reabsorbed and distributed again to the liver. With additional support from a long-term feeding study, these results may suggest innovative foods formulated with oat bran. Increasingly high levels of blood sugar (glucose) are a risk factor of type 2 diabetes, partially due to their ability to increase oxidative damage to cells. Mulberry leaves are part of the traditional Chinese medicine approach to treating diabetes. Phenolic compounds, a class of plant chemicals, in mulberry leaves may protect tissues from oxidative damage. We examined the effect of mulberry leaf phenolics against oxidative damage induced by high glucose concentrations in mouse liver cells in culture. The high glucose increased the production of cellular free radicals that oxidized unsaturated fat in the cells, led to dysfunction of the mitochondria (the source of cellular energy production), and increased biochemical pathways leading to inflammation. Addition of mulberry leaf phenolics prevented these adverse effects of sugar on liver cells. Thus, mulberry leaves may prove a useful ingredient in novel functional foods to protect against the adverse effects of high blood sugar. Flavonoids represent a large class of plant chemicals, non-essential nutrients found in fruits, vegetables, and whole grains that appears to contribute importantly to health. Recent research indicates that flavonoid metabolites produced in the body are the ultimate bioactive forms of these compounds. We examined one metabolic pathway important to flavonoids, UDP-glucuronosyltransferase (UGT), in liver cells taken from adult rats and their offspring to understand how diet may influence flavonoid metabolism and the risk of chronic disease in the offspring. We fed the parents a diet high in fructose and saturated fat before conception and during gestation and lactation. The rat pups were then fed a regular diet until they were grown. UGT activity toward quercetin, a major dietary flavonoid, was determined. We found that high dietary fructose and saturated fat decreases UGT activity toward quercetin in female rats and exposure of the rat fetuses to this diet may decrease UGT activity in female offspring, possibly via an influence on the capacity of their genes to express this enzyme. Vitamin E is an important antioxidant for skin health. We established a 3-dimensional (3D) human skin cell culture that closely models the structure of normal skin. Vitamin E was found to be absorbed into the dermis and epidermis in a dose- and time-dependent manner similar to that found in humans. We tested the ability of vitamin E and almond polyphenols to protect these skin cells against ultraviolet-A (UVA) irradiation as occurs during sun exposure. UVA-induced photodamage of skin structure and cell differentiation was partially prevented by pretreatment with vitamin E or almond polyphenols. We have shown this 3D skin model is a useful tool for assessing the protection of skin against sun damage by dietary ingredients. Nutritional constituents of whole grains other than fiber and vitamins may contribute substantially to their health benefits, but studies examining their bioactivity in humans are limited. To determine the degree to which whole grain oat and barley phytochemicals are absorbed and affect blood sugar and insulin after a meal, we conducted a clinical trial in middle-age and older adults who were overweight or obese. Ferulic acid was found to be better absorbed from oats than barley, and from barley than from the control group consuming refined wheat. Barley and oats had a beneficial effect on the control of blood sugar and also reduced selected biomarkers of inflammation.