Objectives To evaluate the impact of gender and ablation of β-carotene oxygenase 1 (BCO1), β-caro... more Objectives To evaluate the impact of gender and ablation of β-carotene oxygenase 1 (BCO1), β-carotene oxygenase 2(BCO2) or both on tissue accumulation of lycopene dosed transgenic mice. Previous work from our laboratories suggests that BCO2 appears to be the primary carotenoid cleavage enzyme for lycopene in vivo. Methods Three-week old C57BL/6 male and female mice (wild type [WT], Bco1-/-, Bco2-/-, Bco1-/- X Bco2-/- double knock out [DKO]) were divided into groups based on genotype (n = 8 per group/per gender) and fed a powdered AIN 93G diet for 2 weeks. The mice were gavaged daily for 2 weeks with 1 mg of lycopene dissolved in cottonseed oil after which they were fasted and sacrificed. Liver, serum, and extra-hepatic tissues were harvested. Lycopene concentration was measured with high-performance liquid chromatography. Data analyses were performed using one-way ANOVA. Results On a concentration basis, liver, duodenum and adrenal lycopene were higher than other tissues. Serum and ...
Background Vitamin E (α-tocopherol; α-T) deficiency causes spinocerebellar ataxia. α-T supplement... more Background Vitamin E (α-tocopherol; α-T) deficiency causes spinocerebellar ataxia. α-T supplementation improves neurological symptoms, but little is known about the differential bioactivities of natural versus synthetic α-T during early life. Objective We assessed the effects of dietary α-T dose and source on tissue α-T accumulation and gene expression in adolescent α-tocopherol transfer protein-null (Ttpa−/−) mice. Methods Three-week-old male Ttpa−/− mice (n = 7/group) were fed 1 of 4 AIN-93G–based diets for 4 wk: vitamin E deficient (VED; below α-T limit of detection); natural α-T, 600 mg/kg diet (NAT); synthetic α-T, 816 mg/kg diet (SYN); or high synthetic α-T, 1200 mg/kg diet (HSYN). Male Ttpa+/+ littermates fed AIN-93G [75 mg synthetic α-T (CON)] served as controls (n = 7). At 7 wk of age, tissue α-T concentrations and stereoisomer profiles were measured for all groups. RNA-sequencing was performed on cerebella of Ttpa−/− groups. Results Ttpa−/− mice fed VED had undetectable ...
Prostate cancer and prostatic diseases, Jan 25, 2017
Prostate cancer (PCa) is the fifth leading cause of cancer-related deaths worldwide. Many epidemi... more Prostate cancer (PCa) is the fifth leading cause of cancer-related deaths worldwide. Many epidemiological studies have investigated the association between prostate cancer and lycopene, however, results have been inconsistent. This study aims to determine the impact of dietary and circulating concentrations of lycopene on PCa risk and to investigate potential dose-response associations. We conducted a systematic review and dose-response meta-analysis for the for the association between dietary and circulating lycopene and PCa risk. Eligible studies were published before 1 December 2016 and were identified from PubMed, Web of Science and the Cochrane Library. We estimated pooled relative risk ratios (RR) and 95% confidence intervals (CI) using random and fixed effects models. Linear and nonlinear dose-response relationships were also evaluated for PCa risk. Forty-two studies were included in the analysis, which included 43 851 cases of PCa reported from 692 012 participants. Both die...
Lycopene, selenium, and vitamin E are three micronutrients commonly consumed and supplemented by ... more Lycopene, selenium, and vitamin E are three micronutrients commonly consumed and supplemented by men diagnosed with prostate cancer. However, it is not clear whether consumption of these compounds, alone or in combination, results in improved outcomes. We evaluated the effects of dietary lycopene (250 mg/kg diet), selenium (methylselenocysteine, 1 mg/kg diet), and vitamin E (gamma-tocopherol, 200 mg/kg diet) alone and in combination on the growth of androgen-dependent Dunning R3327-H rat prostate adenocarcinomas in male, Copenhagen rats. AIN-93G diets containing these micronutrients were prefed for 4 to 6 weeks prior to tumor implantation by subcutaneous injection. Tumors were allowed to grow for approximately 18 weeks. Across diet groups, methylselenocysteine consumption decreased final tumor area (P = 0.003), tumor weight (P = 0.003), and the tumor weight/body weight ratio (P = 0.003), but lycopene and gamma-tocopherol consumption intake did not alter any of these measures. There ...
1. Carotenoids are 40 carbon pigmented compounds, of which approximately 600 have been identified... more 1. Carotenoids are 40 carbon pigmented compounds, of which approximately 600 have been identified throughout nature. The six main carotenoids found in diet, blood, and tissue are lycopene, β-carotene, α-carotene, β-cryptoxanthin, lutein, and zeaxanthin. 2. The production of retinoids, which promote cell differentiation and inhibit cell proliferation, could be one mechanism for the anticancer activity of carotenoids. However, carotenoids’ multiple
Soy protein was shown to exhibit several beneficial effects on renal function in nondiabetic pati... more Soy protein was shown to exhibit several beneficial effects on renal function in nondiabetic patients with nephropathy, and to improve serum lipids. This study examined the effects of isolated soy protein consumption on urinary albumin excretion, serum lipids, plasma amino acids, and isoflavones in diabetic patients with nephropathy. Male patients (n = 14) with type 2 diabetes and nephropathy were followed in a crossover design for 7 mo. The study comprised two 8-wk intervention periods, placed between a 4-wk lead-in and two 4-wk washout periods. In the 2 intervention periods, 0.5 g/(kg. d) of the dietary protein was provided as either isolated soy protein (ISP) or casein, in random order. Blood and urine samples were collected at the beginning and end of each period. Data were analyzed by multiple linear regression for a repeated-measure design. ISP consumption led to changes of -9.5% in urinary albumin excretion (P < 0.0001), -0.45 in the total-to-HDL-cholesterol ratio (P < ...
The consumption of diets containing 5 to 10 servings of fruits and vegetables daily is the founda... more The consumption of diets containing 5 to 10 servings of fruits and vegetables daily is the foundation of public health recommendations for cancer prevention, yet this concept has not been tested in experimental models of prostate cancer. We evaluated combinations of tomato and broccoli in the Dunning R3327-H prostate adenocarcinoma model. Male Copenhagen rats (n = 206) were fed diets containing 10% tomato, 10% broccoli, 5% tomato plus 5% broccoli (5:5 combination), 10% tomato plus 10% broccoli (10:10 combination) powders, or lycopene (23 or 224 nmol/g diet) for ∼22 weeks starting 1 month prior to receiving s.c. tumor implants. We compared the effects of diet to surgical castration (2 weeks before termination) or finasteride (5 mg/kg body weight orally, 6 d/wk). Castration reduced prostate weights, tumor areas, and tumor weight (62%, P < 0.001), whereas finasteride reduced prostate weights (P < 0.0001), but had no effect on tumor area or weight. Lycopene at 23 or 224 nmol/g of ...
Background Tomatoes contain carotenoids that have the potential to alter the effects of external ... more Background Tomatoes contain carotenoids that have the potential to alter the effects of external beam radiation therapy (EBRT). Objectives We hypothesized that dietary lyophilized tomato paste (TP) would reduce apoptosis within carotenoid-containing nonneoplastic tissues in EBRT-treated TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. Methods Male TRAMP mice (n = 73) were provided an AIN-93G diet or a modified AIN-93G diet containing 10% TP (wt:wt) at 4 wk of age. Prostate tumor growth was monitored by ultrasound. The caudal half of the mouse was irradiated with 7.5 Gy (Rad) or 0 Gy (sham) at 24 wk of age or after the tumor volume exceeded 1000 mm3 with a Cobalt-60 source. Mice were euthanized 24 h postradiation. Carotenoids and α-tocopherol were measured by HPLC and compared by a t test. Tissues were assessed for radiation-induced changes (hematoxylin and eosin) and apoptosis [cleaved caspase-3 (CC3)] and compared by Kruskal–Wallis test or Freedman–Lane's permutati...
Mounting evidence over the past decade suggests that the consumption of fresh and processed tomat... more Mounting evidence over the past decade suggests that the consumption of fresh and processed tomato products is associated with reduced risk of prostate cancer. The emerging hypothesis is that lycopene, the primary red carotenoid in tomatoes, may be the principle phytochemical responsible for this reduction in risk. A number of potential mechanisms by which lycopene may act have emerged, including serving as an important in vivo antioxidant, enhancing cell-to-cell communication via increasing gap junctions between cells, and modulating cell-cycle progression. Although the effect of lycopene is biologically relevant, the tomato is also an excellent source of nutrients, including folate, vitamin C, and various other carotenoids and phytochemicals, such as polyphenols, which also may be associated with lower cancer risk. Tomatoes also contain significant quantities of potassium, as well as some vitamin A and vitamin E. Our laboratory has been interested in identifying specific component...
In vitro lycopene is the most potent antioxidant among carotenoids. While antioxidant function ma... more In vitro lycopene is the most potent antioxidant among carotenoids. While antioxidant function may be relevant to health, we hypothesize that metabolites of lycopene may be bioactive and responsible for the beneficial effects of tomato product consumption. We term these metabolites “lycopenoids, ” which we believe may be produced from carotenoid monooxygenase (CMO) II, paralleling the production of retinoids from β-carotene by CMO I. We present evidence suggesting that tomato carotenoid metabolites may be responsible for the reduced risk of prostate cancer seen in men consuming high levels of tomato products. Finally, we identify gaps in knowledge in this evolving area of carotenoid research.
Epidemiologic investigations support the hypothesis that regular consumption of flavonoid-contain... more Epidemiologic investigations support the hypothesis that regular consumption of flavonoid-containing foods can reduce the risk of cardiovascular diseases (CVD). While flavonoids are ubiquitous in plants, cocoa can be particularly rich in a sub-class of flavonoids known as flavanols. A number of human dietary intervention trials with flavanol-containing cocoa products have demonstrated improvements in endothelial and platelet function, as well as blood pressure. These studies provide direct evidence for the potential cardiovascular benefits of flavanol-containing foods and help to substantiate the epidemiological data. In this review, results from selective published trials with cocoa and chocolate focused on risk for CVD will be discussed along with a study we recently completed evaluating the effects of the daily consumption of flavanol-containing dark chocolate (CocoaVia?) with and without plant sterol esters on CVD markers in a normotensive population with mild hypercholesterolem...
Background Vitamin E (α-tocopherol, α-T) deficiency causes neurological pathologies. α-T suppleme... more Background Vitamin E (α-tocopherol, α-T) deficiency causes neurological pathologies. α-T supplementation improves outcomes, but the relative bioactivities of dietary natural and synthetic α-T in neural tissues are unknown. Objective The aim was to assess the effects of dietary α-T source and dose on oxidative stress and myelination in adult α-tocopherol transfer protein–null (Ttpa−/− ) mouse cerebellum and spinal cord. Methods Three-week-old male Ttpa−/− mice (n = 56) were fed 1 of 4 AIN-93G–based diets for 37 wk: vitamin E–deficient (VED; below α-T limit of detection); natural α-T, 600 mg/kg diet (NAT); synthetic α-T, 816 mg/kg diet (SYN); or high synthetic α-T, 1200 mg/kg diet (HSYN). Male Ttpa+/+littermates (n = 14) fed AIN-93G (75 mg synthetic α-T/kg diet; CON) served as controls. At 40 wk of age, total and stereoisomer α-T concentrations and oxidative stress markers were determined (n = 7/group). Cerebellar Purkinje neuron morphology and white matter areas in cerebellum and spi...
Objectives To evaluate the impact of gender and ablation of β-carotene oxygenase 1 (BCO1), β-caro... more Objectives To evaluate the impact of gender and ablation of β-carotene oxygenase 1 (BCO1), β-carotene oxygenase 2(BCO2) or both on tissue accumulation of lycopene dosed transgenic mice. Previous work from our laboratories suggests that BCO2 appears to be the primary carotenoid cleavage enzyme for lycopene in vivo. Methods Three-week old C57BL/6 male and female mice (wild type [WT], Bco1-/-, Bco2-/-, Bco1-/- X Bco2-/- double knock out [DKO]) were divided into groups based on genotype (n = 8 per group/per gender) and fed a powdered AIN 93G diet for 2 weeks. The mice were gavaged daily for 2 weeks with 1 mg of lycopene dissolved in cottonseed oil after which they were fasted and sacrificed. Liver, serum, and extra-hepatic tissues were harvested. Lycopene concentration was measured with high-performance liquid chromatography. Data analyses were performed using one-way ANOVA. Results On a concentration basis, liver, duodenum and adrenal lycopene were higher than other tissues. Serum and ...
Background Vitamin E (α-tocopherol; α-T) deficiency causes spinocerebellar ataxia. α-T supplement... more Background Vitamin E (α-tocopherol; α-T) deficiency causes spinocerebellar ataxia. α-T supplementation improves neurological symptoms, but little is known about the differential bioactivities of natural versus synthetic α-T during early life. Objective We assessed the effects of dietary α-T dose and source on tissue α-T accumulation and gene expression in adolescent α-tocopherol transfer protein-null (Ttpa−/−) mice. Methods Three-week-old male Ttpa−/− mice (n = 7/group) were fed 1 of 4 AIN-93G–based diets for 4 wk: vitamin E deficient (VED; below α-T limit of detection); natural α-T, 600 mg/kg diet (NAT); synthetic α-T, 816 mg/kg diet (SYN); or high synthetic α-T, 1200 mg/kg diet (HSYN). Male Ttpa+/+ littermates fed AIN-93G [75 mg synthetic α-T (CON)] served as controls (n = 7). At 7 wk of age, tissue α-T concentrations and stereoisomer profiles were measured for all groups. RNA-sequencing was performed on cerebella of Ttpa−/− groups. Results Ttpa−/− mice fed VED had undetectable ...
Prostate cancer and prostatic diseases, Jan 25, 2017
Prostate cancer (PCa) is the fifth leading cause of cancer-related deaths worldwide. Many epidemi... more Prostate cancer (PCa) is the fifth leading cause of cancer-related deaths worldwide. Many epidemiological studies have investigated the association between prostate cancer and lycopene, however, results have been inconsistent. This study aims to determine the impact of dietary and circulating concentrations of lycopene on PCa risk and to investigate potential dose-response associations. We conducted a systematic review and dose-response meta-analysis for the for the association between dietary and circulating lycopene and PCa risk. Eligible studies were published before 1 December 2016 and were identified from PubMed, Web of Science and the Cochrane Library. We estimated pooled relative risk ratios (RR) and 95% confidence intervals (CI) using random and fixed effects models. Linear and nonlinear dose-response relationships were also evaluated for PCa risk. Forty-two studies were included in the analysis, which included 43 851 cases of PCa reported from 692 012 participants. Both die...
Lycopene, selenium, and vitamin E are three micronutrients commonly consumed and supplemented by ... more Lycopene, selenium, and vitamin E are three micronutrients commonly consumed and supplemented by men diagnosed with prostate cancer. However, it is not clear whether consumption of these compounds, alone or in combination, results in improved outcomes. We evaluated the effects of dietary lycopene (250 mg/kg diet), selenium (methylselenocysteine, 1 mg/kg diet), and vitamin E (gamma-tocopherol, 200 mg/kg diet) alone and in combination on the growth of androgen-dependent Dunning R3327-H rat prostate adenocarcinomas in male, Copenhagen rats. AIN-93G diets containing these micronutrients were prefed for 4 to 6 weeks prior to tumor implantation by subcutaneous injection. Tumors were allowed to grow for approximately 18 weeks. Across diet groups, methylselenocysteine consumption decreased final tumor area (P = 0.003), tumor weight (P = 0.003), and the tumor weight/body weight ratio (P = 0.003), but lycopene and gamma-tocopherol consumption intake did not alter any of these measures. There ...
1. Carotenoids are 40 carbon pigmented compounds, of which approximately 600 have been identified... more 1. Carotenoids are 40 carbon pigmented compounds, of which approximately 600 have been identified throughout nature. The six main carotenoids found in diet, blood, and tissue are lycopene, β-carotene, α-carotene, β-cryptoxanthin, lutein, and zeaxanthin. 2. The production of retinoids, which promote cell differentiation and inhibit cell proliferation, could be one mechanism for the anticancer activity of carotenoids. However, carotenoids’ multiple
Soy protein was shown to exhibit several beneficial effects on renal function in nondiabetic pati... more Soy protein was shown to exhibit several beneficial effects on renal function in nondiabetic patients with nephropathy, and to improve serum lipids. This study examined the effects of isolated soy protein consumption on urinary albumin excretion, serum lipids, plasma amino acids, and isoflavones in diabetic patients with nephropathy. Male patients (n = 14) with type 2 diabetes and nephropathy were followed in a crossover design for 7 mo. The study comprised two 8-wk intervention periods, placed between a 4-wk lead-in and two 4-wk washout periods. In the 2 intervention periods, 0.5 g/(kg. d) of the dietary protein was provided as either isolated soy protein (ISP) or casein, in random order. Blood and urine samples were collected at the beginning and end of each period. Data were analyzed by multiple linear regression for a repeated-measure design. ISP consumption led to changes of -9.5% in urinary albumin excretion (P < 0.0001), -0.45 in the total-to-HDL-cholesterol ratio (P < ...
The consumption of diets containing 5 to 10 servings of fruits and vegetables daily is the founda... more The consumption of diets containing 5 to 10 servings of fruits and vegetables daily is the foundation of public health recommendations for cancer prevention, yet this concept has not been tested in experimental models of prostate cancer. We evaluated combinations of tomato and broccoli in the Dunning R3327-H prostate adenocarcinoma model. Male Copenhagen rats (n = 206) were fed diets containing 10% tomato, 10% broccoli, 5% tomato plus 5% broccoli (5:5 combination), 10% tomato plus 10% broccoli (10:10 combination) powders, or lycopene (23 or 224 nmol/g diet) for ∼22 weeks starting 1 month prior to receiving s.c. tumor implants. We compared the effects of diet to surgical castration (2 weeks before termination) or finasteride (5 mg/kg body weight orally, 6 d/wk). Castration reduced prostate weights, tumor areas, and tumor weight (62%, P < 0.001), whereas finasteride reduced prostate weights (P < 0.0001), but had no effect on tumor area or weight. Lycopene at 23 or 224 nmol/g of ...
Background Tomatoes contain carotenoids that have the potential to alter the effects of external ... more Background Tomatoes contain carotenoids that have the potential to alter the effects of external beam radiation therapy (EBRT). Objectives We hypothesized that dietary lyophilized tomato paste (TP) would reduce apoptosis within carotenoid-containing nonneoplastic tissues in EBRT-treated TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. Methods Male TRAMP mice (n = 73) were provided an AIN-93G diet or a modified AIN-93G diet containing 10% TP (wt:wt) at 4 wk of age. Prostate tumor growth was monitored by ultrasound. The caudal half of the mouse was irradiated with 7.5 Gy (Rad) or 0 Gy (sham) at 24 wk of age or after the tumor volume exceeded 1000 mm3 with a Cobalt-60 source. Mice were euthanized 24 h postradiation. Carotenoids and α-tocopherol were measured by HPLC and compared by a t test. Tissues were assessed for radiation-induced changes (hematoxylin and eosin) and apoptosis [cleaved caspase-3 (CC3)] and compared by Kruskal–Wallis test or Freedman–Lane's permutati...
Mounting evidence over the past decade suggests that the consumption of fresh and processed tomat... more Mounting evidence over the past decade suggests that the consumption of fresh and processed tomato products is associated with reduced risk of prostate cancer. The emerging hypothesis is that lycopene, the primary red carotenoid in tomatoes, may be the principle phytochemical responsible for this reduction in risk. A number of potential mechanisms by which lycopene may act have emerged, including serving as an important in vivo antioxidant, enhancing cell-to-cell communication via increasing gap junctions between cells, and modulating cell-cycle progression. Although the effect of lycopene is biologically relevant, the tomato is also an excellent source of nutrients, including folate, vitamin C, and various other carotenoids and phytochemicals, such as polyphenols, which also may be associated with lower cancer risk. Tomatoes also contain significant quantities of potassium, as well as some vitamin A and vitamin E. Our laboratory has been interested in identifying specific component...
In vitro lycopene is the most potent antioxidant among carotenoids. While antioxidant function ma... more In vitro lycopene is the most potent antioxidant among carotenoids. While antioxidant function may be relevant to health, we hypothesize that metabolites of lycopene may be bioactive and responsible for the beneficial effects of tomato product consumption. We term these metabolites “lycopenoids, ” which we believe may be produced from carotenoid monooxygenase (CMO) II, paralleling the production of retinoids from β-carotene by CMO I. We present evidence suggesting that tomato carotenoid metabolites may be responsible for the reduced risk of prostate cancer seen in men consuming high levels of tomato products. Finally, we identify gaps in knowledge in this evolving area of carotenoid research.
Epidemiologic investigations support the hypothesis that regular consumption of flavonoid-contain... more Epidemiologic investigations support the hypothesis that regular consumption of flavonoid-containing foods can reduce the risk of cardiovascular diseases (CVD). While flavonoids are ubiquitous in plants, cocoa can be particularly rich in a sub-class of flavonoids known as flavanols. A number of human dietary intervention trials with flavanol-containing cocoa products have demonstrated improvements in endothelial and platelet function, as well as blood pressure. These studies provide direct evidence for the potential cardiovascular benefits of flavanol-containing foods and help to substantiate the epidemiological data. In this review, results from selective published trials with cocoa and chocolate focused on risk for CVD will be discussed along with a study we recently completed evaluating the effects of the daily consumption of flavanol-containing dark chocolate (CocoaVia?) with and without plant sterol esters on CVD markers in a normotensive population with mild hypercholesterolem...
Background Vitamin E (α-tocopherol, α-T) deficiency causes neurological pathologies. α-T suppleme... more Background Vitamin E (α-tocopherol, α-T) deficiency causes neurological pathologies. α-T supplementation improves outcomes, but the relative bioactivities of dietary natural and synthetic α-T in neural tissues are unknown. Objective The aim was to assess the effects of dietary α-T source and dose on oxidative stress and myelination in adult α-tocopherol transfer protein–null (Ttpa−/− ) mouse cerebellum and spinal cord. Methods Three-week-old male Ttpa−/− mice (n = 56) were fed 1 of 4 AIN-93G–based diets for 37 wk: vitamin E–deficient (VED; below α-T limit of detection); natural α-T, 600 mg/kg diet (NAT); synthetic α-T, 816 mg/kg diet (SYN); or high synthetic α-T, 1200 mg/kg diet (HSYN). Male Ttpa+/+littermates (n = 14) fed AIN-93G (75 mg synthetic α-T/kg diet; CON) served as controls. At 40 wk of age, total and stereoisomer α-T concentrations and oxidative stress markers were determined (n = 7/group). Cerebellar Purkinje neuron morphology and white matter areas in cerebellum and spi...
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Papers by John Erdman