Location: Jean Mayer Human Nutrition Research Center On Aging
2017 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
Reduced Coenzyme Q10 is more absorbable than oxidized Coenzyme Q10. Coenzyme Q10 plays an important role in energy production and exists in both reduced and oxidized states, namely ubiquinol and ubiquinone, respectively. Ubiquinol is also appreciated as an important antioxidant, and in this role, it protects lipids, proteins, and DNA against free radical-induced damages, and recycled oxidized vitamin E. Ubiquinone can be synthesized in the body. Given that older adults have an increased risk of free radical induced-damages and a decreased capability to replenish utilized Coenzyme Q10, we tested whether ubiquinol would be more absorbable than ubiquinone in older adults and if it could confer larger health benefits. Our data indeed showed that as compared to the value before the supplementation, ubiquinol supplement led to a larger improvement in Coenzyme Q10 status as compared to ubiquinone supplement, suggesting the form of Coenzyme Q10 supplement may affect absorption and the overall health effects.
Cranberry modifies the bacteria profile in the gut. Microbes inhabit the human gut and have an intimate symbiotic relationship that affects immunity, metabolism, physiology, and signaling transduction of the host and contributes to disease etiology. While diet is appreciated for its role in disease development and prevention, dietary constituents can affect health indirectly via modulation of the gut microbiota and subsequent production of the primary and secondary products. We examined in a clinical trial whether the addition of cranberry powder to a control diet comprising animal foods and simple carbohydrate foods would affect the microbe profile in the stool of people eating the control diet. We observed that the control diet increased the relative abundance of Firmicutes and decreased Bacteroidetes, but the addition of cranberry powder reversed the changes. Further, as compared to the corresponding baseline, the control diet also decreased R. bromii, B. ovatus, Lachnospira, Anaerostipes, and increased R. gnavus, C. clostridioforme, D. formicigenerans, S. Moorei, Bilophila, Gemella, Actinomycosis, Dorea, and Ruminococcus. We also noted that the cranberry powder increased Anaerostipes and Lachnospira as compared to the control diet. These results suggest that the addition of one polyphenol-rich plant food is capable of shifting the gut microbial composition.
Lutein is protective of docosahexaenoic acid oxidation in the brain of rhesus macaques. Lutein, an antioxidant carotenoid, preferentially accumulates in the brain of primates and is positively related to cognition in humans. Docosahexaenoic acid, an omega-3 polyunsaturated fatty acid, is also beneficial for cognition but is susceptible to oxidation. Thus, we determined the membrane distribution of lutein in brain regions important for different domains of cognitive functions and whether membrane lutein was associated with brain docosahexaenoic acid oxidation in adult rhesus monkeys. All-trans-lutein was detected in all regions and membranes, including prefrontal cortex, cerebellum, striatum, and hippocampus but was highly varied among monkeys. Lutein supplementation significantly increased total concentrations of lutein in serum, prefrontal cortex, and cerebellum. We also noted there was an inverse association between mitochondrial lutein in the prefrontal cortex and striatum and docosahexaenoic acid oxidation products.
Accomplishments
1. Lutein uptake into the brain may depend on age. Lutein, a dietary carotenoid common in fruits and vegetables, selectively accumulates in the human eye and brain. While many studies show evidence of a relationship between lutein in the diet and body tissues (including the brain) and cognitive health, the reason for lutein's selective uptake into human brain tissue is poorly understood. Thus, ARS-funded researchers in Boston, Massachusetts, evaluated whether a known binding protein for lutein would play a role in lutein uptake into the human brain. They measured lutein and the binding protein in the brain and found that there was a strong relationship in infant brains, a significant but weaker relationship in older adults, and an insignificant relationship in centenarians. These findings suggest that a decrease in or abnormal function of lutein's binding protein in the human brain occurs with aging.
Review Publications
Sawicki, C., McKay, D.L., McKeown, N.M., Dallal, G.E., Chen, C., Blumberg, J.B. 2016. Phytochemical pharmacokinetics and bioactivity of oat and barley flour: a randomized crossover trial. Nutrients. 8:813. doi: 10.3390/nu8120813.
Chen, C., Rasmussen, H., Kamil, A., Du, P., Blumberg, J.B. 2017. Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men. Nutrients. 9:130. doi: 10.3390/nu9020130.
Vishwanathan, R., Schalch, W., Johnson, E.J. 2015. Macular pigment carotenoids in the retina and occipital cortex are related in humans. Nutritional Neuroscience. doi: 10.1179/1476830514Y.0000000141.
Martins, I., Roberto, B.S., Blumberg, J.B., Chen, C., Macedo, G. 2016. Enzymatic biotransformation of polyphenolics increases antioxidant activity of red and white grape pomace. Food Research International. 89:533-539.
McKay, D.L., Wilson, T. 2016. Cranberry juice: effects on health. In: Wilson, T.,Temple, N., editors. Beverage Impacts on Health and Nutrition. Switzerland: Springer International. doi: 10.1007/978-3-319-23672-8_7.
