Location: Jean Mayer Human Nutrition Research Center On Aging
2015 Annual Report
Objectives
LAB NAME: Antioxidants Research
Objective 1. Determine the bioavailability, pharmacokinetics, metabolism, and mechanisms of phytochemicals (e.g., carotenoids, phenolic acids, polyphenols) from fruit, nuts, and whole grains using in vitro, animal model, and human studies.
Objective 2. Determine the effect of phytochemicals (e.g., alkylresorcinols, flavonoids) from fruit, nuts, and whole grains on intermediary biomarkers of age-related conditions (e.g., cytokines, isoprostanes), metabolomics parameters (e.g., fatty acids, organic acids), physiological profiles (e.g., endothelial responses, glucose homeostasis), and functional outcomes relevant to cardiovascular disease and type 2 diabetes.
Objective 3. Determine the effect of phytochemicals (e.g., anthocyanins, proanthocyanidins) from fruit, nuts, and whole grains on intermediary biomarkers of age-related conditions (e.g., oxidatively modified DNA) and physiological profiles (e.g., innate immunity) relevant to cancer, particularly colorectal and liver cancers.
Approach
LAB NAME: Antioxidants Research
Using in vitro, animal model, and human studies, we will characterize the bioavailability, pharmacokinetics, metabolism, and mechanisms of phytochemicals (e.g., carotenoids, phenolic acids, polyphenols) from fruit, nuts, and whole grains, particularly as relevant to the aging process and older adults. Building upon this information, we will determine the effect of phytochemicals (e.g., alkylresorcinols, flavonoids) from fruit, nuts, and whole grains on intermediary biomarkers of age-related conditions (e.g., cytokines, isoprostanes), metabolomic parameters (e.g., fatty acids, organic acids), physiological profiles (e.g., endothelial responses, glucose homeostasis), and functional outcomes relevant to cardiovascular disease and type 2 diabetes. In addition, we will investigate the effect of phytochemicals (e.g., anthocyanins, proanthocyanidins) from fruit, nuts, and whole grains on intermediary biomarkers of age-related conditions (e.g., oxidatively modified DNA) and physiological profiles (e.g., innate immunity) relevant to cancer, particularly colorectal and liver cancers.
Progress Report
This report documents research conducted under 1 project in a Non-Assistance Cooperative Agreement between ARS and TUFTS UNIVERSITY. Additional details for the research are associated with project 8050-51000-095-01S, Phytochemicals and
Aging: Bioavailability, Metabolomics, and Bioactivity.
Almonds have been shown to reduce cardiovascular disease risk via reductions in serum cholesterol, inflammation, and oxidative stress. We conducted a randomized, controlled, cross-over trial to determine whether the addition of 3 ounces of almonds daily to a National Cholesterol Education Program Step 1 (NCEP) diet for 6 weeks would improve vascular function and inflammation in 45 older adults with coronary artery disease. All the subjects were maintained on their usual drug treatment regimens. The addition of almonds to the NCEP diet increased plasma vitamin E, but altered neither vascular function (assessed by flow-mediated dilation and related measures) nor serum lipid profile, blood pressure, or biomarkers of inflammation. However, the almond intervention did improve the overall quality of the diet by increasing calcium, magnesium, choline, and fiber intake to or above recommended intakes. In conclusion, the addition of almonds to a NECP diet did not significantly impact vascular function, lipid profile, or systemic inflammation in patients with coronary artery disease who were receiving good medical care and polypharmacy therapies, but did improve diet quality without any untoward effect.
Skin is the largest organ in the human body and is exposed to an array of environmental insults. Among them, ultraviolet light (UV) is thought to be the most harmful because cumulative UV exposure can cause oxidative stress, inflammation, redness of the skin, wrinkling, and non-melanoma and melanoma skin cancer. Almonds are among the richest dietary sources of vitamin E and also contain an array of antioxidant polyphenols. These nutrients may serve to increase the skin’s defenses against UV (photoprotection). We assessed whether vitamin E and polyphenols could protect a model of human skin from UV-induced damage. After the human skin (derived from foreskin) was treated with vitamin E or polyphenols, the skin was irradiated with UV. The UV exposure decreased skin cell growth, increased cell death, and disorganized skin structure. However, these UV-induced harmful changes were alleviated by vitamin E or polyphenols. In conclusion, vitamin E and polyphenols present in almonds might provide some degree of photoprotection against UV in human skin.
Lutein is a fat-soluble carotenoid found especially in green leafy vegetables, corn, and egg yolks but is characterized as having a low bioavailability. Delivery of lutein via polymeric nanoparticles presents a novel approach to enhancing lutein bioavailability. We evaluated the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enhance lutein uptake and transport in human gastrointestinal cells in culture and lutein bioavailability and distribution in rats. Compared to free lutein, encapsulation of lutein in nanoparticles increased maximal plasma concentration and bioavailability in rats by over 50-fold, while promoting tissue accumulation in mesenteric adipose and spleen. However, in cell culture, lutein nanoparticles were a less effective form of delivery than lutein in micelles, the way they are transported in vivo. In conclusion, the nanodelivery of lutein with polymeric nanoparticles appears to be a promising approach to improve the bioavailability of this carotenoid.
Shalgam juice is a dark red-colored and sour fermented beverage produced and consumed in Turkey. Commercially available shalgam juice is made from black carrots, a source of anthocyanin flavonoids (from which we measured cyanidin-3-galactoside, cyanidin-3-glucoside, and cyanidin-3-arabinoside) as well as other phenolic compounds providing antioxidant capacity, demonstrated via three different assays (ABTS, DPPH, FRAP). We also identified a total of 21 Lactobacillus bacteria using species-specific polymerase chain reaction assays. These results suggest the shalgam juice possess high antioxidant capacity and may also provide a dietary source of probiotic bacteria.
The benefit of antioxidant micronutrients for slowing the progression to advanced stages of age-related macular degeneration was supported by the two Age-Related Eye Disease Studies (AREDS): 4 daily tablets utilized in AREDS1 and 2 daily softgels in AREDS2. However, the choice of excipient, dosage form, and ingredient chemistry as well as patient physiology and pathologies can influence the bioavailability and efficacy of the supplement. So, we explored the influence of dosage form on bioavailability of the five primary AREDS1 and AREDS2 micronutrients: the metals zinc and copper, beta-carotene, and vitamins E and C. Fifteen healthy men and women were recruited into a randomized crossover trial of the AREDS1 micronutrients and the pharmacokinetic profile established for each ingredient/dosage form in plasma or serum over the course of one week. Results suggest modestly contradictory requirements in dosage form for water-soluble and lipid-soluble ingredients, based on a goal of improved bioavailability. Comparative consistency in bioavailability was observed across dosage forms and most nutrients between AREDS1 and AREDS2 formulations relative to the significant variations observed within this controlled population. These results emphasize the importance of defining the bioavailability for each micronutrient and the influence of dosage form. With the recognition of global and population-specific micronutrient deficiencies, notably in the elderly populations afflicted with age-related macular degeneration, and their metabolic and health consequences, establishing efficient means of dietary supplementation remains an important research goal.
A high glucose milieu promotes generation of free radicals which can cause cellular damage, but may also modulate phase II enzymes which are responsible for the metabolism of flavonoids. We examined the effect of a high glucose concentrations in vitro on the metabolism of the flavonoid quercetin in human liver cells. Four major quercetin metabolites were observed in the culture medium and inside the liver cells. Quercetin and its metabolites were reduced in cells grown in high, compared to normal, glucose concentrations in the culture media. Addition of a flavonoid anthocyanidin (as a natural antioxidant) or superoxide dismutase plus catalase did not prevent or enhance the reduction of quercetin metabolites. Thus, in vitro, a high glucose milieu decreases the production of the principal metabolite quercetin in human liver cells mediated via mechanisms that appear independent of oxidative stress.
Oxidative stress is an early response to the restriction of blood supply to the brain and may to play an important role in the development of injury after a stroke. We sought to evaluate whether a biomarker of oxidative stress (plasma and urinary isoprostanes) and antioxidant defenses, which can be affected by dietary antioxidants, can predict infarct growth in patients presenting with acute ischemic stroke. Baseline levels of isoprostanes were significantly correlated with infarct growth and volume. These results suggest the potential for nutritional interventions to reduce the severity of the consequences of a stroke.
Accomplishments
1. Cranberry juice protects against inflammation and improves vascular function in healthy but overweight adults. Clinical trials with cranberry products have mainly focused on urinary tract health. ARS funded researchers at the Jean Mayer USDA Human Nutrition Center on Aging in Boston, Massachusetts, studied the effects of chronic cranberry beverage consumption on oxidative damage, inflammation, and vascular (endothelial) function in 78 healthy but overweight adults. The subjects consumed 15.2 oz. daily of a placebo or a high cranberry polyphenol beverage for 8 weeks in a randomized, double-blind trial. Scientists found that a single dose of the cranberry beverage could improve redox status and vascular function, while chronic consumption caused a reduction in inflammatory biomarkers. These outcomes suggest that cranberry polyphenols may reduce the risk of cardiovascular disease.
2. Urinary alkylresorcinols may be useful biomarkers of whole wheat intake. Alkylresorcinols (AR) are phenolic lipids present in the bran of wheat and rye, and they, along with their urinary metabolites, may be suitable biomarkers of whole-grain consumption. ARS funded researchers at the Jean Mayer USDA Human Nutrition Center on Aging in Boston, Massachusetts, examined plasma AR and urinary AR metabolites in response to whole wheat consumption in a randomized crossover trial with 3 or 6 servings of whole wheat daily incorporated into the regular diet for 1 week. Urinary AR metabolites were significantly higher after the 6 than the 3 daily servings of whole wheat. This dose-response relationship was independent of age, sex, energy intake, and baseline urinary AR metabolite level. Plasma total AR tended to be higher after 6 than 3 daily servings. The results suggest that urinary AR metabolites may be useful as biomarkers of compliance in intervention studies of whole wheat.
