Background α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-co... more Background α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-controlled clinical trials in otherwise healthy, overweight adults using LA supplementation are lacking. Objectives The primary objective was to evaluate whether LA supplementation decreases elevated plasma triglycerides in overweight or obese adults. Secondary aims examined if LA promotes weight loss and improves oxidative stress and inflammation. Methods Overweight adults [n = 81; 57% women; 21–60 y old; BMI (in kg/m2) ≥ 25] with elevated plasma triglycerides ≥100 mg/dL were enrolled in a 24-wk, randomized, double-blind, controlled trial, assigned to either (R)-α-lipoic acid (R-LA; 600 mg/d) or matching placebo, and advised not to change their diet or physical activity. Linear models were used to evaluate treatment effects from baseline for primary and secondary endpoints. Results R-LA did not decrease triglyceride concentrations, but individuals on R-LA had a greater reduction in BMI at...
Are Extension healthy youth programs needed in highly educated U.S. communities? To answer this q... more Are Extension healthy youth programs needed in highly educated U.S. communities? To answer this question, 175 children from four public elementary schools in Corvallis, Oregon, self-reported in a crosssectional study their dietary intake, and 71 children provided a blood sample for measuring vitamin D concentrations. Most children had insufficient blood vitamin D and reported a diet insufficient in fiber, essential fatty acids, potassium, and vitamin E and excessive in saturated fatty acids and sodium. Our data indicate a need for Extension to provide youth programs in highly educated U.S. communities to improve nutrient intakes and vitamin D status in children.
Objectives Micronutrient inadequacies are common in older adults. We sought to assess if multivit... more Objectives Micronutrient inadequacies are common in older adults. We sought to assess if multivitamin/multimineral supplement (MVM) use improved micronutrient intake and biomarker status among older adults enrolled in NHANES. Methods The National Cancer Institute Method was used to estimate usual intakes of 18 micronutrients stratified by age and frequency of MVM use. Insufficiency and deficiency prevalence were evaluated using nutrient biomarkers. Results Compared with food alone, MVM use was associated with higher nutrient intake and lower prevalence of inadequacies of almost all micronutrients exam- ined and improved nutrient biomarker status of folate, iodine, selenium, and vitamins B6, B12, and D. Regular MVM use (!16days/month) decreased the odds of clinical deficiency (defined by biomarker status) of vitamins B6 and D but increased the proportion exceeding the tolerable upper intake level of folic acid. Vitamin B6 deficiency in MVM non-users was common and increased with age....
The intracellular distribution of Ca2+ and, in particular, the level of cytosolic free Ca2+ are k... more The intracellular distribution of Ca2+ and, in particular, the level of cytosolic free Ca2+ are known to be extremely important in the regulation of many cellular processes, including metabolism, motility, exocytosis, membrane transport, and cell division [1, 2]. In many cells, such as hepatocytes, the cytosolic free Ca2+ concentration is thought to be controlled through the concerted action of Ca2+ transport systems located in the membranes of mitochondria [3], endoplasmatic reticulum [4], and plasmalemma [5].
Fruits from 107 genotypes of Vaccinium L., Rubus L., and Ribes L., were analyzed for total anthoc... more Fruits from 107 genotypes of Vaccinium L., Rubus L., and Ribes L., were analyzed for total anthocyanins (ACY), total phenolics (TPH), and antioxidant capacities as determined by oxygen radical absorbing capacity (ORAC) and ferric reducing antioxidant power (FRAP). Fruit size was highly correlated (r) 0.84) with ACY within Vaccinium corymbosum L., but was not correlated to ACY across eight other Vaccinium species, or within 27 blackberry hybrids. Certain Vaccinium and Ribes fruits with pigmented flesh were lower in ACY, TPH, ORAC, and FRAP compared to those values in berries with nonpigmented flesh. ORAC values ranged from 19 to 131 µmol Trolox equivalents/g in Vaccinium, from 13 to 146 in Rubus, and from 17 to 116 in Ribes. Though ACY may indicate TPH, the range observed in ACY/TPH ratios precludes prediction of ACY from TPH and vice versa for a single genotype. In general, TPH was more highly correlated to antioxidant capacity than ACY was. This study demonstrates the wide diversity of phytochemical levels and antioxidant capacities within and across three genera of small fruit.
Critical Reviews in Food Science and Nutrition, 2003
Increasing interest in the health benefits of tea has led to the inclusion of tea extracts in die... more Increasing interest in the health benefits of tea has led to the inclusion of tea extracts in dietary supplements and functional foods. However, epidemiologic evidence regarding the effects of tea consumption on cancer and cardiovascular disease risk is conflicting. While tea contains a number of bioactive chemicals, it is particularly rich in catechins, of which epigallocatechin gallate (EGCG) is the most abundant. Catechins and their derivatives are thought to contribute to the beneficial effects ascribed to tea. Tea catechins and polyphenols are effective scavengers of reactive oxygen species in vitro and may also function indirectly as antioxidants through their effects on transcription factors and enzyme activities. The fact that catechins are rapidly and extensively metabolized emphasizes the importance of demonstrating their antioxidant activity in vivo. In humans, modest transient increases in plasma antioxidant capacity have been demonstrated following the consumption of tea and green tea catechins. The effects of tea and green tea catechins on biomarkers of oxidative stress, especially oxidative DNA damage, appear very promising in animal models, but data on biomarkers of in vivo oxidative stress in humans are limited. Larger human studies examining the effects of tea and tea catechin intake on biomarkers of oxidative damage to lipids, proteins, and DNA are needed.
Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, an... more Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV. These effects correlated with increased reactive oxygen species (ROS) levels that favored CAV1-induced migration and invasion. Interestingly, pY14-CAV1 promoted the metabolic switch associated with increased migration/invasion and augmented ROS-inhibited PTP1B, a phosphatase that controls pY14 levels. Finally, the glycolysis inhibitor 2-deoxy-D-glucose reduced CAV1-enhanced migration in vitro and metastasis in vivo of murine melanoma cells. In conclusion, CAV1 promo...
Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the ... more Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the Lcat gene in the mouse is associated with dramatic decreases in HDL concentration and the accumulation of nascent HDL in the plasma. We examined whether LCAT deficiency in mice is associated with a concomitant decrease in two antioxidative enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). In control Lcat (؉ / ؉) mice both these enzymes are transported on HDL. Compared to Lcat (؉ / ؉) mice, HDL-cholesterol is reduced 94% and apoA-I, 90%, in Lcat (؊ / ؊) mice; this reduction in HDL is paralleled by a 71% decrease in PAF-AH activity and in a 58% decrease in PON activity. Apolipoprotein J (apoJ) levels, rather than being decreased, were significantly (P ؍ 0.01) higher (36%) in Lcat (؊ / ؊) than in Lcat (؉ / ؉) mice, and the apo J/PON ratio was 3-fold greater in Lcat (؊ / ؊) than in Lcat (؉ / ؉) animals. Even though apolipoprotein A-I (apoA-I) concentration and PON activity were drastically reduced, there was no reduction in apoA-I and PON liver mRNA levels suggesting that post-transcriptional events are responsible for the reduction of plasma PON and apoA-I levels. Fast protein liquid chromatography (FPLC) revealed that in Lcat (؉ / ؉) mice both PON and PAF-AH activity is associated with large, apoA-I-containing HDL particles (9.7 nm by non-denaturing gradient gel electrophoresis) while in Lcat (؊ / ؊) mice both enzymes are associated with small 8.2 nm particles. We conclude that the concomitant reduction in HDL and apoA-I concentrations and PON and PAF-AH activities is best explained by rapid clearance of the small HDL particles found in LCAT deficiency.-Forte, T.
A nutritional study was initiated to determine which carotenoids found in tomato result in decrea... more A nutritional study was initiated to determine which carotenoids found in tomato result in decreased lipid oxidation ex vivo. To compare the carotenoids in a human diet without the use of purified supplements, tomatoes expressing nonfunctional enzymes in the carotenoid pathway were used. Tomato lines carrying the genes t, B, ogc, Del, or r were grown to produce fruit containing with high levels of prolycopene, beta-carotene, lycopene, or delta-carotene respectively, or low total carotenoids in r. Juices were processed from these lines and used in a dietary intervention study. Plasma samples were drawn before and after consumption of each juice. These samples were subjected to a battery of tests to analyze the contribution of carotenoids to the total lipid antioxidant status. Results of these tests are discussed.
Atherosclerosis, the underlying cause of ischemic heart disease and stroke, is an inflammatory di... more Atherosclerosis, the underlying cause of ischemic heart disease and stroke, is an inflammatory disease of arteries in a hyperlipidemic milieu. Endothelial expression of cellular adhesion molecules, such as endothelial-leukocyte adhesion molecule-1 (E-selectin) and intercellular adhesion molecule-1 (ICAM-1), plays a critical role in the initiation and progression of atherosclerosis. The dietary flavonoid, quercetin, has been reported to inhibit expression of cellular adhesion molecules, but the underlying mechanisms are incompletely understood. In this study, we found that quercetin dose-dependently (5-20µM) inhibits lipopolysaccharide (LPS)-induced mRNA and protein expression of E-selectin and ICAM-1 in human aortic endothelial cells (HAEC). Incubation of HAEC with quercetin also significantly reduced LPS-induced oxidant production, but did not inhibit activation of the nuclear factor-kappaB (NF-κB). Furthermore, quercetin induced activation of the nuclear factor erythroid 2-related...
Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to... more Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to delayed tissue damage following traumatic spinal cord injury (SCI). Ubiquinols (reduced coenzyme Q), ascorbate (vitamin C), and alpha-tocopherol (vitamin E) are endogenous antioxidants; decreases in tissue levels of these compounds may, therefore, reflect ongoing oxidative reactions. In the present studies, alterations in tissue levels of ubiquinol-9 and -10, ascorbate, and alpha-tocopherol were examined after SCI of varying severity in the rat. Levels of alpha-tocopherol did not change significantly after injury. Ascorbate and ubiquinol levels were decreased after trauma. Changes in tissue levels of ubiquinol, but not ascorbate reflected the degree of trauma. Thus, ubiquinol levels may provide a useful marker of the oxidative component of the secondary injury response.
Background α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-co... more Background α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-controlled clinical trials in otherwise healthy, overweight adults using LA supplementation are lacking. Objectives The primary objective was to evaluate whether LA supplementation decreases elevated plasma triglycerides in overweight or obese adults. Secondary aims examined if LA promotes weight loss and improves oxidative stress and inflammation. Methods Overweight adults [n = 81; 57% women; 21–60 y old; BMI (in kg/m2) ≥ 25] with elevated plasma triglycerides ≥100 mg/dL were enrolled in a 24-wk, randomized, double-blind, controlled trial, assigned to either (R)-α-lipoic acid (R-LA; 600 mg/d) or matching placebo, and advised not to change their diet or physical activity. Linear models were used to evaluate treatment effects from baseline for primary and secondary endpoints. Results R-LA did not decrease triglyceride concentrations, but individuals on R-LA had a greater reduction in BMI at...
Are Extension healthy youth programs needed in highly educated U.S. communities? To answer this q... more Are Extension healthy youth programs needed in highly educated U.S. communities? To answer this question, 175 children from four public elementary schools in Corvallis, Oregon, self-reported in a crosssectional study their dietary intake, and 71 children provided a blood sample for measuring vitamin D concentrations. Most children had insufficient blood vitamin D and reported a diet insufficient in fiber, essential fatty acids, potassium, and vitamin E and excessive in saturated fatty acids and sodium. Our data indicate a need for Extension to provide youth programs in highly educated U.S. communities to improve nutrient intakes and vitamin D status in children.
Objectives Micronutrient inadequacies are common in older adults. We sought to assess if multivit... more Objectives Micronutrient inadequacies are common in older adults. We sought to assess if multivitamin/multimineral supplement (MVM) use improved micronutrient intake and biomarker status among older adults enrolled in NHANES. Methods The National Cancer Institute Method was used to estimate usual intakes of 18 micronutrients stratified by age and frequency of MVM use. Insufficiency and deficiency prevalence were evaluated using nutrient biomarkers. Results Compared with food alone, MVM use was associated with higher nutrient intake and lower prevalence of inadequacies of almost all micronutrients exam- ined and improved nutrient biomarker status of folate, iodine, selenium, and vitamins B6, B12, and D. Regular MVM use (!16days/month) decreased the odds of clinical deficiency (defined by biomarker status) of vitamins B6 and D but increased the proportion exceeding the tolerable upper intake level of folic acid. Vitamin B6 deficiency in MVM non-users was common and increased with age....
The intracellular distribution of Ca2+ and, in particular, the level of cytosolic free Ca2+ are k... more The intracellular distribution of Ca2+ and, in particular, the level of cytosolic free Ca2+ are known to be extremely important in the regulation of many cellular processes, including metabolism, motility, exocytosis, membrane transport, and cell division [1, 2]. In many cells, such as hepatocytes, the cytosolic free Ca2+ concentration is thought to be controlled through the concerted action of Ca2+ transport systems located in the membranes of mitochondria [3], endoplasmatic reticulum [4], and plasmalemma [5].
Fruits from 107 genotypes of Vaccinium L., Rubus L., and Ribes L., were analyzed for total anthoc... more Fruits from 107 genotypes of Vaccinium L., Rubus L., and Ribes L., were analyzed for total anthocyanins (ACY), total phenolics (TPH), and antioxidant capacities as determined by oxygen radical absorbing capacity (ORAC) and ferric reducing antioxidant power (FRAP). Fruit size was highly correlated (r) 0.84) with ACY within Vaccinium corymbosum L., but was not correlated to ACY across eight other Vaccinium species, or within 27 blackberry hybrids. Certain Vaccinium and Ribes fruits with pigmented flesh were lower in ACY, TPH, ORAC, and FRAP compared to those values in berries with nonpigmented flesh. ORAC values ranged from 19 to 131 µmol Trolox equivalents/g in Vaccinium, from 13 to 146 in Rubus, and from 17 to 116 in Ribes. Though ACY may indicate TPH, the range observed in ACY/TPH ratios precludes prediction of ACY from TPH and vice versa for a single genotype. In general, TPH was more highly correlated to antioxidant capacity than ACY was. This study demonstrates the wide diversity of phytochemical levels and antioxidant capacities within and across three genera of small fruit.
Critical Reviews in Food Science and Nutrition, 2003
Increasing interest in the health benefits of tea has led to the inclusion of tea extracts in die... more Increasing interest in the health benefits of tea has led to the inclusion of tea extracts in dietary supplements and functional foods. However, epidemiologic evidence regarding the effects of tea consumption on cancer and cardiovascular disease risk is conflicting. While tea contains a number of bioactive chemicals, it is particularly rich in catechins, of which epigallocatechin gallate (EGCG) is the most abundant. Catechins and their derivatives are thought to contribute to the beneficial effects ascribed to tea. Tea catechins and polyphenols are effective scavengers of reactive oxygen species in vitro and may also function indirectly as antioxidants through their effects on transcription factors and enzyme activities. The fact that catechins are rapidly and extensively metabolized emphasizes the importance of demonstrating their antioxidant activity in vivo. In humans, modest transient increases in plasma antioxidant capacity have been demonstrated following the consumption of tea and green tea catechins. The effects of tea and green tea catechins on biomarkers of oxidative stress, especially oxidative DNA damage, appear very promising in animal models, but data on biomarkers of in vivo oxidative stress in humans are limited. Larger human studies examining the effects of tea and tea catechin intake on biomarkers of oxidative damage to lipids, proteins, and DNA are needed.
Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, an... more Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV. These effects correlated with increased reactive oxygen species (ROS) levels that favored CAV1-induced migration and invasion. Interestingly, pY14-CAV1 promoted the metabolic switch associated with increased migration/invasion and augmented ROS-inhibited PTP1B, a phosphatase that controls pY14 levels. Finally, the glycolysis inhibitor 2-deoxy-D-glucose reduced CAV1-enhanced migration in vitro and metastasis in vivo of murine melanoma cells. In conclusion, CAV1 promo...
Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the ... more Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the Lcat gene in the mouse is associated with dramatic decreases in HDL concentration and the accumulation of nascent HDL in the plasma. We examined whether LCAT deficiency in mice is associated with a concomitant decrease in two antioxidative enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). In control Lcat (؉ / ؉) mice both these enzymes are transported on HDL. Compared to Lcat (؉ / ؉) mice, HDL-cholesterol is reduced 94% and apoA-I, 90%, in Lcat (؊ / ؊) mice; this reduction in HDL is paralleled by a 71% decrease in PAF-AH activity and in a 58% decrease in PON activity. Apolipoprotein J (apoJ) levels, rather than being decreased, were significantly (P ؍ 0.01) higher (36%) in Lcat (؊ / ؊) than in Lcat (؉ / ؉) mice, and the apo J/PON ratio was 3-fold greater in Lcat (؊ / ؊) than in Lcat (؉ / ؉) animals. Even though apolipoprotein A-I (apoA-I) concentration and PON activity were drastically reduced, there was no reduction in apoA-I and PON liver mRNA levels suggesting that post-transcriptional events are responsible for the reduction of plasma PON and apoA-I levels. Fast protein liquid chromatography (FPLC) revealed that in Lcat (؉ / ؉) mice both PON and PAF-AH activity is associated with large, apoA-I-containing HDL particles (9.7 nm by non-denaturing gradient gel electrophoresis) while in Lcat (؊ / ؊) mice both enzymes are associated with small 8.2 nm particles. We conclude that the concomitant reduction in HDL and apoA-I concentrations and PON and PAF-AH activities is best explained by rapid clearance of the small HDL particles found in LCAT deficiency.-Forte, T.
A nutritional study was initiated to determine which carotenoids found in tomato result in decrea... more A nutritional study was initiated to determine which carotenoids found in tomato result in decreased lipid oxidation ex vivo. To compare the carotenoids in a human diet without the use of purified supplements, tomatoes expressing nonfunctional enzymes in the carotenoid pathway were used. Tomato lines carrying the genes t, B, ogc, Del, or r were grown to produce fruit containing with high levels of prolycopene, beta-carotene, lycopene, or delta-carotene respectively, or low total carotenoids in r. Juices were processed from these lines and used in a dietary intervention study. Plasma samples were drawn before and after consumption of each juice. These samples were subjected to a battery of tests to analyze the contribution of carotenoids to the total lipid antioxidant status. Results of these tests are discussed.
Atherosclerosis, the underlying cause of ischemic heart disease and stroke, is an inflammatory di... more Atherosclerosis, the underlying cause of ischemic heart disease and stroke, is an inflammatory disease of arteries in a hyperlipidemic milieu. Endothelial expression of cellular adhesion molecules, such as endothelial-leukocyte adhesion molecule-1 (E-selectin) and intercellular adhesion molecule-1 (ICAM-1), plays a critical role in the initiation and progression of atherosclerosis. The dietary flavonoid, quercetin, has been reported to inhibit expression of cellular adhesion molecules, but the underlying mechanisms are incompletely understood. In this study, we found that quercetin dose-dependently (5-20µM) inhibits lipopolysaccharide (LPS)-induced mRNA and protein expression of E-selectin and ICAM-1 in human aortic endothelial cells (HAEC). Incubation of HAEC with quercetin also significantly reduced LPS-induced oxidant production, but did not inhibit activation of the nuclear factor-kappaB (NF-κB). Furthermore, quercetin induced activation of the nuclear factor erythroid 2-related...
Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to... more Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to delayed tissue damage following traumatic spinal cord injury (SCI). Ubiquinols (reduced coenzyme Q), ascorbate (vitamin C), and alpha-tocopherol (vitamin E) are endogenous antioxidants; decreases in tissue levels of these compounds may, therefore, reflect ongoing oxidative reactions. In the present studies, alterations in tissue levels of ubiquinol-9 and -10, ascorbate, and alpha-tocopherol were examined after SCI of varying severity in the rat. Levels of alpha-tocopherol did not change significantly after injury. Ascorbate and ubiquinol levels were decreased after trauma. Changes in tissue levels of ubiquinol, but not ascorbate reflected the degree of trauma. Thus, ubiquinol levels may provide a useful marker of the oxidative component of the secondary injury response.
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