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.

The potential role of soyfoods in weight and adiposity reduction: an evidence-based review.

Evidence concerning the relationship between soyfoods and weight loss was reviewed. Detailed searches of PubMed and Web of Science were performed to identify and evaluate evidence for or against four propositions related to soyfoods and weight loss (Data from in vitro, animal, epidemiologic, and clinical studies were evaluated and summarized). (1) Certain soyfoods will improve weight and/or fat loss when fed at isolcaloric levels (similar calories given across experimental conditions, but not necessarily at a level to maintain current body weight); generally supportive evidence in animal studies, but there is no compelling support in human studies. (2) Certain soyfoods will improve weight and fat loss when included as part of a diet by affecting caloric intake; limited supportive evidence in animal and human studies. (3) Certain soyfoods will prevent/improve risk factors related to glucoregulatory function and cardiovascular health during weight loss; some evidence supporting this proposition, but additional evidence is needed before conclusions can be made. (4) Certain soyfoods will minimize the loss of bone mass during weight loss; no data available pertinent to this proposition. Limitations in existing data make it difficult to reach conclusions regarding these four propositions. Overall, the current data suggest that soyfoods are as good as other protein sources for promoting weight loss and there is a suggestive body of evidence that soyfoods may confer additional benefits, but results must be carefully interpreted and additional evidence is needed before making firm conclusions concerning soyfoods and weight loss.

Use of packaged entrees as part of a weight-loss diet in overweight men: an 8-week randomized clinical trial.

AIM: This study assessed the efficacy of a weight-loss diet by using packaged portion-controlled entrees vs. a self-selected diet based on the United States Department of Agriculture Food Guide Pyramid (FGP). METHODS: Sixty healthy overweight men (body mass index (BMI) 26-42 kg/m2; aged 24-60 years) were randomized into two groups for an 8-week intervention. Group E consumed two portion-controlled entrees daily, plus recommended servings from the FGP. Group P consumed a self-selected diet consisting of a recommended number of servings from the FGP. Diets were designed to be isocaloric (1700 kcal) and identical in macronutrient composition (55% carbohydrate, 25% protein and 20% fat). Participants were instructed to make no changes in physical activity levels. Each group was blinded to the protocol of the other group, and received separate diet instructions, but no behavioural or diet counselling. Outcomes included weight, BMI, body composition by dual energy X-ray absorptiometry, waist and hip circumference, blood pressure (BP), fasting blood lipids, glucose, insulin and C-reactive protein. RESULTS: Fifty-one men completed the study. The portion-control group E (n = 25) experienced greater decreases in weight (-7.4 +/- 3.1 vs. -5.1 +/- 4.0 kg), BMI (-2.4 +/- 1.0 vs. -1.6 +/- 1.3 kg/m2), fat mass (-3.6 +/- 1.8 vs. -2.5 +/- 1.8 kg), waist circumference (-6.6 +/- 3.3 vs. -4.3 +/- 2.9 cm) and diastolic BP (-6.0 +/- 7.2 vs. + 0.2 +/- 10.1 mmHg) than group P (n = 26) (p < 0.05). Consumption of a packaged entree diet resulted in greater losses of weight and fat mass, and reduced BP. CONCLUSIONS: Use of packaged entrees as part of a weight-loss diet is an effective means of achieving portion control and enhancing losses of weight and fat mass in overweight men.

Testosterone and food restriction modulate hepatic lycopene isomer concentrations in male F344 rats.

We previously demonstrated that the castration of male rats profoundly increases hepatic lycopene compared with intact controls. Here we further characterized the role of testosterone in modulating hepatic lycopene accumulation and isomer patterns in male rats. Furthermore, because castration significantly decreases ad libitum food consumption, we investigated the influence of food restriction on lycopene metabolism. Forty male F344 rats 8 wk of age were randomly assigned to one of four treatments (n = 10/group): 1) intact, free access to food, 2) castration, free access to food, 3) castration plus testosterone implants, free access to food and 4) intact, 20% food restricted. All rats were fed an AIN-based diet with 0.25 g lycopene (as 10% water-soluble beadlets)/kg diet for 3 wk. Serum testosterone was 5.31 +/- 1.46 nmol/L in intact controls allowed free access to food, reduced in castrated animals (0.52 +/- 0.10, P < 0.0001 versus controls) and intact, food-restricted rats (1.53 +/- 0.49 nmol/L, P < 0.0001 versus controls) and greater (17.23 +/- 3.09 nmol/L) in castrated rats administered testosterone (P < 0.0001 versus controls). Castrated rats accumulated approximately twice as much liver lycopene (74.5 +/- 8.5 nmol/g; P < 0.01 versus controls) as intact rats allowed free access to food (39.5 +/- 5.0) despite 13% lower dietary lycopene intake (P < 0.001; 3.38 +/- 0.07 versus 3.95 +/- 0.06 mg lycopene/d). Testosterone replacement in castrated rats returned liver lycopene concentrations (32.5 +/- 5.5 nmol lycopene/g with 3.76 +/- 0.05 mg dietary lycopene/d) to those observed in intact rats. Food restriction resulted in a 20% decrease in lycopene intake but significantly increased liver lycopene by 68% (66.3 +/- 7.9 nmol lycopene/g with 3.38 +/- 0.00 mg lycopene/d) compared with controls and castrated rats administered testosterone. These results suggest that androgen depletion and 20% food restriction increase hepatic lycopene accumulation. We hypothesize an endocrine and dietary interaction, where higher androgen concentrations and greater energy intake may stimulate lycopene metabolism and degradation.

Nutrition: a reservoir for integrative science.

In the last twenty years, powerful new molecular techniques were introduced that made it possible to advance knowledge in human biology using a reductionist approach. Now, the need for scientists to deal with complexity should drive a movement toward an integrationist approach to science. We propose that nutritional science is one of the best reservoirs for this approach. The American Society for Nutritional Sciences can play an important role by developing and delivering a cogent message that convinces the scientific establishment that nutrition fills this valuable niche. The society must develop a comprehensive strategy to develop our image as the reservoir for life sciences integration. Our efforts can start with our national meeting and publications, with the research initiatives for which we advocate, with our graduate training programs and with the public relations image we project for ourselves. Defining the image and future directions of nutrition as the discipline that can integrate scientific knowledge from the cell and molecule to the whole body and beyond to populations can be the most important task that our society undertakes. If we do not effectively meet this challenge, a golden opportunity will pass to others and nutritional scientists will be left to follow them.

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.

Amount of dietary fat and type of soluble fiber independently modulate postabsorptive conversion of beta-carotene to vitamin A in mongolian gerbils.

Current dietary guidelines recommend a decrease in fat intake and an increase in fiber consumption. Decreased bioavailability (BV) of carotenoids is thought to be associated with both of these recommendations. A 2 x 4 factorial design was used to test the effects of dietary fat level at 10 or 30% of total energy and fiber type using no fiber, silica, citrus pectin or oat gum (7 g/100 g) on beta-carotene (betaC) BV in 4- to 5-wk-old Mongolian gerbils. We assessed BV as both accumulation of betaC and bioconversion of betaC to vitamin A (VA) in tissues. A VA- and betaC-deficient diet was fed for 1 wk followed by one of eight isocaloric, semipurified diets supplemented with carrot powder [ approximately 1 microgram betaC, 0.5 microgram alpha-carotene (alphaC)/kJ diet] for 2 wk (n = 12/group). Increasing dietary fat resulted in higher VA (P: = 0.074) and lower betaC (P: = 0.0001) stores in the liver, suggesting that consumption of high fat diets enhances conversion of betaC to VA. The effect of soluble fiber on hepatic VA storage was dependent on fiber type. Consumption of citrus pectin resulted in lower hepatic VA stores and higher hepatic betaC stores compared with all other groups, suggesting less conversion of betaC to VA. In contrast, consumption of oat gum resulted in hepatic VA and betaC stores that were higher (P = 0.012) and lower (P = 0.022), respectively, than those of citrus pectin-fed gerbils. The level of dietary fat consumed with soluble fiber had no interactive effects on hepatic VA, betaC or alphaC stores. Results demonstrate that betaC BV is independently affected by dietary fat level and type of soluble fiber, and suggest that these dietary components modulate postabsorptive conversion of betaC to VA. This study confirms the negative effects of citrus pectin on betaC BV, and suggests that oat gum does not adversely affect betaC BV.

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.

Influence of dietary vitamin A content on serum and liver vitamin A concentrations and health in preruminant Holstein calves fed milk replacer.

Evidence has suggested that the current requirement for vitamin A tabulated by the NRC [(approximately 3800 IU of vitamin A/kg of dry matter (DM)] for dairy calves fed liquid diets is too low. The objective of this study was to assess the effects of vitamin A content in milk replacers on serum and liver vitamin A concentrations, growth, and development of clinical signs of vitamin A deficiency in calves. Male Holstein calves were separated from their dams at birth and given standardized feedings of colostrum and milk replacer for 3 d. On d 4, calves were assigned to five groups and fed milk replacer containing 2300, 6200, 9000, 18,300, or 44,000 IU of vitamin A/kg of DM. Liver biopsies and serum samples were taken on d 4, 9, 15, 21, and 28 to monitor vitamin A concentrations. Weekly physical and neurological examinations were performed to monitor the development of deficiency signs. Fecal scores, body temperature, and the presence of nasal and ocular discharge were recorded daily. Liver vitamin A concentrations in calves allotted to diets with 2300 and 6200 IU of vitamin A/kg decreased from d 4 to 28. Calves fed 9000 IU of vitamin A/kg maintained liver stores, while those fed 18,300 and 44,000 IU of vitamin A/kg had significant increases in hepatic vitamin A. A strong negative association existed between incidence of hyperthermic temperatures and vitamin A concentration in the diet; calves fed 2300 IU of vitamin A/kg had approximately three times more hyperthermic readings than did calves fed other treatments. A strong negative association also existed between fecal score and concentration of vitamin A in the diet; calves fed diets containing low vitamin A concentration had a higher incidence of high fecal scores (more watery) than did calves fed diets with higher vitamin A concentrations. Although slight differences were detected in serum retinol concentration, growth performance and incidence of ocular and nasal discharges were not different among treatment groups. Our data indicate that vitamin A concentrations of less than 9000 IU/kg of DM in milk replacers result in declining liver vitamin A stores in preruminant calves. Using the human Dietary Reference Intakes as a model for calculating the requirement, we recommend that the vitamin A requirement for preruminant calves should be increased to 11,000 IU of vitamin A/kg of DM.

beta-Carotene stability and uptake by prostate cancer cells are dependent on delivery vehicle.

Cell culture systems provide an opportunity to evaluate the effects of carotenoids on molecular and cellular processes involved in proliferation and differentiation of prostate cancer cells. The stability and cellular uptake of beta-carotene (BC) by prostate cancer cells were investigated in vitro by use of various delivery methods and three human prostate adenocarcinoma cell lines: PC-3, DU 145, and LNCaP. Recovery of BC from the media (prepared from water-dispersible BC beadlets) significantly (p < 0.05) decreased after 12 hours in culture and continued to significantly decrease (p < 0.05) after 24, 48, 72, and 96 hours, an observation primarily attributed to BC degradation rather than isomerization, metabolism, or cellular uptake. The uptake of BC by prostate cancer cells was compared when delivered by tetrahydrofuran, BC-enriched bovine serum, water-dispersible BC beadlets, and artificial liposomes. Recovery of BC after three days in culture from enriched bovine serum medium was significantly (p < 0.05) greater than recovery from medium prepared by beadlets, tetrahydrofuran, or artificial liposomes. We conclude that BC is relatively unstable in vitro and that degradation products may contribute to biological responses. Furthermore, our studies indicate that enriched bovine serum provides a stable and physiological approach to carotenoid treatment of cells in culture.

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.

Tissue lycopene concentrations and isomer patterns are affected by androgen status and dietary lycopene concentration in male F344 rats.

Diets rich in lycopene from tomato products as well as greater concentrations of blood lycopene have been associated with a decreased risk for prostate cancer in epidemiologic studies. However, little is known about factors modulating lycopene absorption, metabolism and tissue distribution in humans and animal models of prostate cancer. A 2 x 4 factorial design was used to measure the effects of androgen status (castrated vs. intact), dietary lycopene concentration (0.00-5.00 g/kg lycopene) and their interaction on tissue lycopene accumulation and isomer patterns in male F344 rats. Male F344 rats ( 14 wk old; 44 castrated, 44 intact) were randomly assigned to one of four diets containing total lycopene concentrations of 0.00, 0.05, 0.50 or 5.00 g/kg as beadlets and fed for 8 wk. Tissue total lycopene and cis/trans lycopene profiles were determined by HPLC. Tissue and serum lycopene concentrations increased significantly (P < 0.01) as dietary lycopene levels increased between 0.00 and 0.50 g/kg. No further increases in serum or tissue concentrations were seen in rats fed dietary lycopene between 0.50 and 5.00 g/kg. As dietary lycopene increased, so did the percentage of cis lycopene in the liver (P < 0.05), due primarily to an increase in the 5-cis isomer. Castrated rats accumulated twice (P < 0.01) the liver lycopene as compared to intact controls, with no effect of castration on serum lycopene or adrenal, kidney, adipose, or lung tissue concentration. Livers from castrated rats had a greater proportion of cis-lycopene than those of intact rats (P < 0.05). A significant interaction between dietary lycopene concentration and androgen status was seen for liver lycopene concentration (P < 0.01). We conclude that serum and tissue lycopene reaches a plateau between 0.05 and 0.50 g/kg dietary lycopene, the tissue cis/trans lycopene ratio increases with greater dietary lycopene and androgens modulate hepatic lycopene metabolism.

Beta-carotene modulates human prostate cancer cell growth and may undergo intracellular metabolism to retinol.

Epidemiologic and animal studies provide support for a relationship between high intakes of carotenoids from fruits and vegetables with reduced risk of several malignancies including prostate cancer. The highly controlled environments of in vitro systems provide an opportunity to investigate the cellular and molecular effects of carotenoids. The effects of beta-carotene (BC) on in vitro growth rates, p21(WAF1) and p53 gene expression, as well as the conversion of BC to retinol were investigated in three human prostate adenocarcinoma cell lines: PC-3, DU 145 and LNCaP. In these experiments, media concentrations of 30 micromol BC/L for 72 h significantly (P < 0.05) slowed in vitro growth rates in all three cell lines, independently of p53 or p21(WAF1) status or expression. (14)C-labeled retinol was detected in prostate tumor cells incubated with (14)C-labeled BC, suggesting metabolic conversion of BC to retinol. Conversely, no (14)C-labeled retinol was detected in media incubated without prostate cancer cells. These studies support a hypothesis that in vitro biological effects of BC on prostate cells may result in part from the conversion of BC to retinol or other metabolites. The possibility that prostate cancer cells in vivo locally metabolize provitamin A carotenoids to retinol and other related metabolites may have implications for our understanding of prostate cancer etiology and the design of future prevention studies.

Review of animal models in carotenoid research.

Foods containing provitamin A carotenoids are the primary source of vitamin A in many countries, despite the poor bioavailability of carotenoids. In addition, epidemiologic studies suggest that dietary intake of carotenoids influences the risk for certain types of cancer, cardiovascular disease and other chronic diseases. Although it would be ideal to use humans directly to answer critical questions regarding carotenoid absorption, metabolism and effects on disease progression, appropriate animal models offer many advantages. This paper will review recent progress in the development of animal models with which to study this class of nutrients. Each potential model has strengths and weaknesses. Like humans, gerbils, ferrets and preruminant calves all absorb beta-carotene (betaC) intact, but only gerbils and calves convert betaC to vitamin A with efficiency similar to that of humans. Mice and rats efficiently convert betaC to vitamin A but absorb carotenoids intact only when they are provided in the diet at supraphysiologic levels. Mice, rats and ferrets can be used to study cancer, whereas primates and gerbils are probably more appropriate for studies on biomarkers of heart disease. No one animal model completely mimics human absorption and metabolism of carotenoids; thus the best model must be chosen with consideration of the specific application being studied, characteristics of the model, and the available funding and facilities.