Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: Forty-two studies were included in the analysis, which included 43 851 cases of PCa reported from 692 012 participants. Both dietary intake (RR=0.88, 95% CI: 0.78-0.98, P=0.017) and circulating concentrations (RR=0.88, 95% CI: 0.79-0.98, P=0.019) of lycopene were significantly associated with reduced PCa risk. Sensitivity analyses within the dose-response analysis further revealed a significant linear dose-response for dietary lycopene and PCa risk such that PCa decreased by 1% for every additional 2 mg of lycopene consumed (P=0.026). Additionally, PCa risk decreased by 3.5 to 3.6% for each additional 10 µgdl-1 of circulating lycopene in the linear and nonlinear models respectively (plinear=0.004, pnonlinear=0.006). While there were no associations between lycopene and advanced PCa, there was a trend for protection against PCa aggressiveness (RR=0.74, 95% CI: 0.55-1.00, P=0.052). CONCLUSIONS: Our data demonstrate that higher dietary and circulating lycopene concentrations are inversely associated with PCa risk. This was accompanied by dose-response relationships for dietary and circulating lycopene. However, lycopene was not associated with a reduced risk of advanced PCa. Further studies are required to determine the mechanisms underlying these associations.

Alterations in calcium intake on peak bone mass in the female rat.

This study compared the effect of a calcium deficit or surfeit on bone growth and development in the early phase of peak bone mass attainment with the late phase of peak bone mass attainment using the female Sprague-Dawley rat as a model. Groups of weanling animals were fed one of three nutritionally complete but calcium-altered diets (0.25%, 0.5%, or 1.0% calcium) for 8 weeks. Animals within each diet group were then rerandomized into one of the above diets and fed until 37 weeks of age. Each group contained five rats. In addition, three groups that received the 0.25% calcium diet for the first 8 weeks remained on the diet until week 20 when they were further randomized into one of the three diet groups and fed until 37 weeks of age. Results of this experiment indicate that increasing the calcium intake after adolescence (12-weeks-old) of those female rats consuming a low calcium diet will not substantially alter the adult bone volume of the metaphyseal region of the proximal tibia. Further, low calcium intakes through adolescence retard and prolong longitudinal bone growth. In contrast, however, those rats fed a diet providing calcium either at (0.5%) or twice the National Research Council's requirement level through adolescence had greater tibial bone volume as an adult when fed diets containing 1.0% calcium after this time period. It appears that the mechanism for this increase involves both a protection from resorption and an increase in bone formation/mineralization. This study is the first to show that low calcium intakes through adolescence have a nonreversible, deleterious effect on peak bone mass, whereas higher intakes promote greater peak bone mass and provide potential protection from age-related bone loss.

Soy products and the human diet.

This review focuses upon the nutritional significance of soy products in the human diet. The impact of the consumption of soy foods on a range of diet and health issues are discussed, including protein quality and growth promoting effects of soy protein, allergies in children, hypocholesterolemic effects of soy protein and soy fiber, effects of soy products upon glucose tolerance, and the bioavailability of zinc and iron from soy foods. Recent research reports involving humans and relevant animal studies are reviewed.

Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men.

BACKGROUND: Replacing animal protein with soy protein has been shown to reduce total and LDL-cholesterol concentrations in humans. However, the minimum amount of soy protein required for significant reduction of blood lipids is not known. OBJECTIVE: We evaluated the amount of soy protein needed to reduce blood lipids in moderately hypercholesterolemic men. DESIGN: Eighty-one men with moderate hypercholesterolemia (total cholesterol concentration between 5.70 and 7.70 mmol/L) were studied. After a 3-wk lead-in on a Step I diet, total cholesterol was measured and subjects were randomly divided into 5 groups. For 6 wk, each group received 50 g protein/d, which included isolated soy protein (ISP) and casein, respectively, in the following amounts: 50:0, 40:10, 30:20, 20:30, and 0:50 (control group) g. Blood was collected at baseline and weeks 3 and 6 of the intervention. RESULTS: At week 6, significant reductions (P < 0.05) from baseline compared with the control group were found for non-HDL and total cholesterol and apolipoprotein (apo) B for all ISP groups (except total cholesterol with 40 g ISP). At week 3, significant reductions (P < 0.05) were found in apo B for the groups that consumed >/=30 g ISP and in non-HDL cholesterol for the groups that consumed >/=40 g ISP. HDL-cholesterol, apo A-I, lipoprotein(a), and triacylglycerol concentrations were not significantly affected by dietary treatment. CONCLUSION: Our findings show that consuming as little as 20 g soy protein/d instead of animal protein for 6 wk reduces concentrations of non-HDL cholesterol and apo B by approximately 2.6% and 2.2%, respectively. 2000;71:-84.

Alterations in vitamin A and thyroid hormone status in anorexia nervosa and associated disorders.

Vitamin A and thyroid hormone status was investigated in 27 patients with anorexia nervosa. Subjects were divided into three groups based on eating behavior and serum carotene concentrations: anorexic (dietary restriction), normal carotene; anorexic, elevated serum carotene; bulimic, elevated serum carotene. All bulimic subjects fulfilling selection criteria were hypercarotenemic (weight loss and reduced metabolic rate). Data were compared to normal healthy volunteers. Serum retinol and retinol-binding protein levels were normal in all subjects whereas retinyl esters were elevated in the hypercarotenemic groups. Hypercarotenemia was primarily a result of elevation of vitamin A active carotenoids, especially beta-carotene. Diet was excluded from the etiology of hypercarotenemia. Thyroid hormones T4 and T3 were significantly depressed in hypercarotenemic groups and rT3 increased. A concomitant alteration in vitamin-hormone status is observed with progressive metabolic alterations: low T3, T4, and elevated retinyl esters in subjects with the hypercarotenemia associated with anorexia nervosa.

Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women.

The effects of soy protein (40 g/d) containing moderate and higher concentrations of isoflavones on blood lipid profiles, mononuclear cell LDL receptor messenger RNA, and bone mineral density and content were investigated in 66 free-living, hypercholesterolemic, postmenopausal women during a 6-mo, parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, during which subjects followed a National Cholesterol Education Program Step I low-fat, low-cholesterol diet, all subjects were randomly assigned to 1 of 3 dietary groups: Step I diet with 40 g protein/d obtained from casein and nonfat dry milk (CNFDM), Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein (ISP56), or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein (ISP90). Total and regional bone mineral content and density were assessed. Non-HDL cholesterol for both ISP56 and ISP90 groups was reduced compared with the CNFDM group (P < 0.05). HDL cholesterol increased in both ISP56 and ISP90 groups (P < 0.05). Mononuclear cell LDL receptor mRNA was increased in subjects consuming ISP56 or ISP90 compared with those consuming CNFDM (P < 0.05). Significant increases occurred in both bone mineral content and density in the lumbar spine but not elsewhere for the ISP90 group compared with the control group (P < 0.05). Intake of soy protein at both isoflavone concentrations for 6 mo may decrease the risk factors associated with cardiovascular disease in postmenopausal women. However, only the higher isoflavone-containing product protected against spinal bone loss.

Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women.

The long-term clinical effects of soy protein containing various amounts of isoflavones on lipoproteins, mononuclear cell LDL receptor messenger RNA concentrations, and other selected cardiovascular risk factors are not well known. Sixty-six hypercholesterolemic, free-living, postmenopausal women were investigated during a 6-mo parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, all subjects were randomly assigned to 1 of 3 dietary groups (all with 40 g protein): a National Cholesterol Education Program (NCEP) Step 1 diet with protein from casein and nonfat dry milk (control), an NCEP Step 1 diet with protein from isolated soy protein containing moderate amounts of isoflavones (ISP56), or an NCEP Step 1 diet with protein from isolated soy protein containing high amounts of isoflavones (ISP90). Non-HDL cholesterol in both the ISP56 and ISP90 groups was reduced compared with the control group (P < 0.05), whereas total cholesterol was not changed. HDL cholesterol increased in both the ISP56 and ISP90 groups (P < 0.05), whereas the ratio of total to HDL cholesterol decreased significantly in both groups compared with the control (P < 0.05). Mononuclear cell LDL receptor messenger RNA concentrations increased in subjects consuming ISP56 or ISP90 compared with the control (P < 0.05). These results indicate that soy protein, with different amounts of isoflavones, may decrease the risk of cardiovascular disease via improved blood lipid profiles, and that the mechanism by which apolipoprotein B-containing lipoproteins were depressed may be via alterations in LDL receptor quantity or activity.

cis-trans lycopene isomers, carotenoids, and retinol in the human prostate.

An evaluation of the Health Professionals Follow-Up Study has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene, a non-provitamin A carotenoid with potent antioxidant activity. Our goal was to define the concentrations of lycopene, other carotenoids, and retinol in paired benign and malignant prostate tissue from 25 men, ages 53 to 74, undergoing prostatectomy for localized prostate cancer. The concentrations of specific carotenoids in the benign and malignant prostate tissue from the same subject are highly correlated. Lycopene and all-trans beta-carotene are the predominant carotenoids observed, with means +/- SE of 0.80 +/- 0.08 nmol/g and 0.54 +/- 0.09, respectively. Lycopene concentrations range from 0 to 2.58 nmol/g, and all-trans beta-carotene concentrations range from 0.09 to 1.70 nmol/g. The 9-cis beta-carotene isomer, alpha-carotene, lutein, alpha-cryptoxanthin, zeaxanthin, and beta-cryptoxanthin are consistently detectable in prostate tissue. No significant correlations between the concentration of lycopene and the concentrations of any other carotenoid are observed. In contrast, strong correlations between prostate beta-carotene and alpha-carotene are noted (correlation coefficient, 0.88; P < 0.0001), as are correlations between several other carotenoid pairs, which reflects their similar dietary origins. Mean vitamin A concentration in the prostate is 1.52 nmol/g, with a range of 0.71 to 3.30 nmol/g. We further evaluated tomato-based food products, serum, and prostate tissue for the presence of geometric lycopene isomers using high-performance liquid chromatography with a polymeric C30 reversed phase column. All-trans lycopene accounts for 79 to 91% and cis lycopene isomers for 9 to 21% of total lycopene in tomatoes, tomato paste, and tomato soup. Lycopene concentrations in the serum of men range between 0.60 and 1.9 nmol/ml, with 27 to 42% all-trans lycopene and 58 to 73% cis-isomers distributed among 12 to 13 peaks, depending upon their chromatographic resolution. In striking contrast with foods, all-trans lycopene accounts for only 12 to 21% and cis isomers for 79 to 88% of total lycopene in benign or malignant prostate tissues. cis Isomers of lycopene within the prostate are distributed among 14 to 18 peaks. We conclude that a diverse array of carotenoids are found in the human prostate with significant intra-individual variation. The presence of lycopene in the prostate at concentrations that are biologically active in laboratory studies supports the hypothesis that lycopene may have direct effects within the prostate and contribute to the reduced prostate cancer risk associated with the reduced prostate cancer risk associated with the consumption of tomato-based foods. The future identification and characterization of geometric lycopene isomers may lead to the development of novel agents for chemoprevention studies.

Vitamin A deficiency reduces uptake of beta-carotene by brush border membrane vesicles but does not alter intestinal retinyl ester hydrolase activity in the rat.

Vitamin A deficiency has been reported to result in mild structural and functional changes within the small intestine. The objective of this study was to measure the impact of vitamin A deficiency in the rat on several functional aspects of beta-carotene uptake and intestinal retinyl ester hydrolysis. These included uptake of (14)C-beta-carotene by brush border membrane vesicles (BBMV) and in vitro activity of intrinsic retinyl ester hydrolase (REH). Rats (n = 33) were randomly assigned to receive one of three dietary treatments: vitamin A deficient (-VA), vitamin A sufficient pair-fed (PF), or vitamin A sufficient free access-fed (FA). Liver, serum retinol, and growth data were used to verify clinical vitamin A deficiency. Rats in the -VA group were clinically vitamin A deficient by Day 56 on a vitamin A-free diet and, at that point, all rats were randomly assigned to one of two experimental treatments: BBMV studies or REH activity assays. Uptake of (14)C-beta-carotene by BBMV was significantly suppressed (P < 0.05) in -VA rats when compared to both PF and FA control rats during early passive uptake equilibration (10-20 sec). Uptake was also significantly decreased by BBMV isolated from -VA rats compared to PF controls, but not FA controls, after a 10-min incubation (P < 0.05). In vitro activity of REH was not impacted by vitamin A deficiency in rats, although a trend for greater activity from -VA rats was noted. These data suggest that vitamin A deficiency impairs enterocyte membrane uptake of beta-carotene without altering the enzymatic activity of intrinsic REH.

Contributions of exercise, body composition, and age to bone mineral density in premenopausal women.

The purpose of this cross-sectional study were to determine whether exercisers have greater bone mineral density (BMD) than nonexercisers, whether aerobic dancers have greater BMD than walkers, and to determine the contributions of energy expenditure, body composition, and dietary factors to spine and femur BMD. Measurements were obtained on 93 eumenorrheic women (walkers N = 28; aerobic dancers, N = 34; nonexercisers, N = 31) ages 25-41 yr; lumbar spine and proximal femur BMD, body composition, physical activity, and nutrient intakes. Mean height, weight, and body mass index and median age and calcium intakes were similar for the three groups. Mean (+/- SD) values of the spine, total femur, and femoral neck BMD, respectively, were: walkers (1.092 (+/- 0.098), 0.947 g.cm-2), dancers (1.070 (+/- 0.124), 0.990 (+/- 0.104), 0.908 (+/- 0.106) g.cm-2), and nonexercisers (1.020 (+/- 0.112), 0.887 (+/- 0.073), 0.792 (+/- 0.089) g.cm-2) multiple regression analyses indicated that exercise contributed to spine (P = 0.018), total femur (P =0.012), and femoral neck (P < 0.0001) BMD, whereas type of exercise (aerobic dance vs walking) did not (P > 0.05). Total femoral BMD was influenced by exercise (P = 0.012) and energy expenditure (P = 0.023), while vertebral BMD was influenced by age (P = 0.0067), body weight (P = 0.017), and exercise (P = 0.018). These findings suggest that walking and aerobic dance exercise may provide physically active premenopausal women with greater lumbar and femoral BMD than sedentary females.

Use of the modified relative dose response (MRDR) assay in rats and its application to humans for the measurement of vitamin A status.

After an appropriate dose of 3,4-didehydroretinol (vitamin A2, DR) is given orally in corn oil to retinol (R)-depleted rats, the ratio of plasma DR/R values at 3.5 h is inversely related to the liver concentration of vitamin A (Tanumihardjo & Olson, 1988). In the present study, a similar procedure, termed the modified relative dose response (MRDR) assay, was employed with rats containing a much broader range of liver reserves; ie, less than 2 to 107 nmol of vitamin A per g wet weight of liver (less than 1 to 30 micrograms/g). The DR/R ratio for 15 of 16 rats with liver reserves less than 17 nmol/g (less than 5 micrograms/g) was greater than 0.15, whereas the ratio was less than 0.15 for 7 of 8 rats with liver reserves greater than 17 nmol/g. This distribution provides sensitivity, specificity and positive predictive values of 94, 88 and 94 per cent, respectively. The DR/R ratios reached a maximal plateau in two other groups of rats between 3.5 and 8 h. At all times up to 24 h, mean DR/R ratios for vitamin A-depleted rats (45 +/- 6 nmoles of vitamin A/g liver) were approximately twice those for vitamin A-sufficient rats (230 +/- 40 nmoles of vitamin A/g liver). In three well-nourished adults, presumably with liver reserves of greater than 300 nmol/g wet weight liver (greater than 80 micrograms retinol equivalents/g), and in two young (1- and 3-years old) well-nourished children, maximal DR/R ratios were less than 0.023. In these cases, peak DR/R ratios were observed, with one possible exception, between 8 and 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperlipidemia in rats fed retinoic acid.

This report describes a series of experiments that attempt to characterize the lipidemia accompanying retinoic acid administration. After feeding young adult male Sprague-Dawley rats, 1.2 Retinol Equivalents (R.E.) retinyl acetate plus supplemental retinoic acid (100 microgram/g dry diet) for three days and fasting for 6-8 hr, triglyceride, cholesterol, and phospholipid content of various serum lipoprotein fractions were determined. When compared to unsupplemented controls, both the serum very low density lipoprotein (VLDL) and the high density lipoprotein (HDL) fractions of the retinoic acid-fed rats were found to harbor an elevated triglyceride content. While VLDL cholesterol and phospholipid content were also elevated, total serum cholesterol and phospholipids were not statistically altered. The detergent Triton WR-1339 was used to depress serum triglyceride clearance in order to assess the effects of retinoic acid feeding on serum triglyceride levels. Triglyceride accumulation started earlier after Triton treatment and was greater when rats were fed 100 microgram/g retinoic acid for three days prior to testing. Red and white gastrocnemius muscle, cardiac ventricular muscle, and perirenal adipose tissue were removed from rats following retinoic acid feeding. Analysis of these tissues for lipoprotein lipase (EC 3.1.1.3) activity showed a decrease in adipose tissue, a large depression in both areas of gastrocnemius muscle and no change in cardiac muscle as a result of retinoic acid feeding.

Vitamin A induced hypertriglyceridemia in cholesterol-fed rats.

The effects of level and feeding frequency of retinoic acid (OIC) or retinyl acetate (YL) on the accumulation of lipids in the serum and liver of rats were investigated. Male Sprague-Dawley rats were fed ad libitum 1% cholesterol diets with or without supplemental OIC or YL. Vitamin A-fed groups included (per g of dry diet): 105 microgram of OIC or 113 microgram YL daily for 28 days, 735 microgram OIC or 791 microgram YL once each week for 28 days; and 735 or 105 microgram OIC on day 1 or 105 microgram OIC daily for the week experiment. Daily feeding of OIC or YL increased serum triglyceride concentrations as compared to conrols. Several days after removal of OIC or 1 week after removal of supplemental YL from the rat diets, serum triglyceride concentrations returned to basal levels. Cholesterol feeding elevated serum cholesterol as well as hepatic cholesterol, total lipids and vitamin A concentrations. Daily OIC feeding depressed serum and hepatic cholesterol concentrations. These results show that daily supplement of vitamin A increased serum triglycerides and reduced serum and hepatic cholesterol concentrations. Serum and liver alterations were dependent on continued feeding.

Determination of lycopene, alpha- and beta-carotene and retinyl esters in human serum by reversed-phase high performance liquid chromatography.

A rapid specific, microdetermination of the major human blood carotenoids by high performance liquid chromatography (HPLC) separation and quantitation at 466 nm is detailed in this paper. Serum retinyl esters can also be quantified utilizing the same separation procedure but detected at 325 nm. One hundred microliters of deproteinated serum were extracted with chloroform and injected on a reverse-phase column. Separation occurred within 16 min for all compounds of interest employing a mobile solvent of MeOH/AcN/CHCl3 (47:47:6). All compounds were quantified at the wavelengths cited by integrated peak areas using retinyl acetate as a daily standard. Analysis of serum from a hypercarotenemic anorexia nervosa patient and a person suffering from hypervitaminosis A are presented as examples of the clinical application of this procedure.

Technical note: a technique for multiple liver biopsies in neonatal calves.

Our objective was to develop a rapid and safe liver biopsy technique that could be repeated on multiple occasions in individual neonatal calves. A pilot study was performed to verify the efficacy of sedation and restraint procedures and to evaluate different biopsy instruments. Following the pilot experiment, a biopsy trocar was fabricated and an experiment was conducted using this procedure. Liver biopsies were performed in neonatal calves on d 4, 9, 15, 21, and 28 of life to evaluate the effect of vitamin A intake on liver vitamin A concentrations. On these days, a single injection of ceftiofur sodium was administered i.m. 1 to 2 h prior to the procedure. Calves were lightly sedated with xylazine and placed on a surgical table in left-lateral recumbency. The right caudo-thoracic area was clipped and scrubbed with an iodophor agent. Following administration of a local anesthetic (lidocaine), a small incision was made in the skin between the 12th and 13th ribs approximately 15 cm from the dorsal midline. The biopsy trocar was inserted through the body wall and peritoneum and introduced into the liver parenchyma, and a liver sample was collected. Following the biopsy, the cutaneous incision was sutured and an antiseptic agent was applied to prevent infection. An i.m. injection of an analgesic was administered 1 h following the procedure to alleviate postsurgical discomfort. Most calves were able to stand within 2 h after the biopsy. The entire procedure, which could be performed by a single individual, usually required about 20 min from initial sedation until skin closure. Although liver samples of up to 500 mg were obtained, most samples weighed 75 to 150 mg (wet weight). A total of 156 liver biopsies were performed on 33 calves. Complications due to the biopsy procedure were observed in only two calves. Therefore, this procedure can be useful for studies designed to monitor changes in liver composition or enzyme activities over time.

Hydrated sodium calcium aluminosilicate: effects on zinc, manganese, vitamin A, and riboflavin utilization.

Three experiments were conducted to evaluate effects of hydrated sodium calcium aluminosilicate (HSCAS, a phyllosilicate) on Zn, Mn, vitamin A, and riboflavin utilization in young broiler chicks. In Experiment 1, addition of either .5% or 1.0% HSCAS to practical corn-soybean meal diets had no effect (P greater than .05) on total tibia Mn content or total liver vitamin A concentration. Total tibia Zn decreased slightly, but linearly (P less than .05), as level of HSCAS increased. Graded increments of riboflavin (0, .6 and 1.2 mg per kg of diet) were added to a riboflavin-free purified amino acid diet to assess riboflavin utilization as affected by HSCAS in Experiments 2 (.5% HSCAS) and 3 (1.0% HSCAS). Linear growth responses to riboflavin were obtained in the absence and presence of HSCAS. Common intercept multiple-linear regression indicated that riboflavin utilization was not affected (P greater than .05) by .5% or 1.0% HSCAS. The results suggest that .5% or 1.0% dietary HSCAS does not impair Mn, vitamin A, or riboflavin utilization, but that Zn utilization is reduced slightly as a result of HSCAS ingestion.