Nutrient Cost-Effectiveness of Fortified Blended Food Aid Products.

BACKGROUND: Sorghum-Soy Blend (SSB) and Sorghum-Cowpea Blend (SCB) fortified blended food aid porridge products were developed as alternatives to Corn-Soy Blend Plus (CSB+) and Super Cereal Plus (SC+), the most widely used fortified blended food aid products. However, the cost and nutrient cost-effectiveness of these products procured from different geographical areas have not been determined. OBJECTIVE: The objective of this study is to determine the nutrient cost-effectiveness of SSB and SCB compared to existing fortified blended foods. METHODS: Nutritional data as well as ingredient, processing, and transportation cost for SSB, SCB, and existing fortified blended foods were compiled. Using the omega value, the ratio of the fortified blended food's Nutrient Value Score to the total cost of the fortified blended food divided by an identical ratio of a different fortified blended food or the same fortified blended food produced in a different country and the nutrient cost-effectiveness of each of the fortified blended foods procured in the United States and several African countries were determined. RESULTS: Both CSB+ and SC+ are less expensive than SSB and SCB, but they also have lower Nutrient Value Scores of 7.7 and 8.6, respectively. However, the omega values of CSB+ and SC+ are all above 1 when compared to SSB and SCB, suggesting that the existing fortified blended foods are more nutrient cost-effective. CONCLUSIONS: Comparing the nutrient cost-effectiveness of various food aid products could provide valuable information to food aid agencies prior to making procurement decisions.

Salivary Cystatin SN Binds to Phytic Acid In Vitro and Is a Predictor of Nonheme Iron Bioavailability with Phytic Acid Supplementation in a Proof of Concept Pilot Study.

BACKGROUND: Acute phytic acid intake has been found to decrease iron bioavailability; however, repeated phytic acid consumption leads to iron absorption adaptation. Salivary proline-rich proteins (PRPs) have been shown to inhibit iron chelation to tannins and may mediate similar iron absorption adaptation with phytic acid intake. OBJECTIVES: The objectives of this study were to determine whether salivary proteins bind to phytic acid in vitro, and to explore a proof of concept in a pilot study that examined the impact of 4-wk, daily phytic acid supplementation on individuals' iron status, bioavailability, and salivary PRP concentrations. METHODS: High-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization-time of flight were used to characterize in vitro salivary protein-phytic acid interactions. Nonanemic women (n = 7) consumed 350 mg phytic acid supplements 3 times daily for 4 wk, and meal challenges were employed to determine iron bioavailability, iron status, and salivary protein concentrations before and after supplementation periods. Enzyme-linked immunosorbent assay (ELISA) analysis of purified protein fractions and participant saliva identified proteins bound to phytic acid. RESULTS: In vitro salivary protein-phytic acid interaction identified cystatin SN, a non-proline rich salivary protein, as the specific bound protein to phytic acid. Iron bioavailability (P = 0.32), hemoglobin (P = 0.72), and serum ferritin (P = 0.08) concentrations were not reduced from week 0 to week 4 after phytic acid supplementation. Basic PRPs and cystatin SN concentrations were positively correlated with iron bioavailability at week 4. CONCLUSIONS: Overall, results suggest that phytic acid binds to the non-PRP cystatin SN and that salivary protein production may improve iron bioavailability with phytic acid consumption.

Complementary Feeding of Sorghum-Based and Corn-Based Fortified Blended Foods Results in Similar Iron, Vitamin A, and Anthropometric Outcomes in the MFFAPP Tanzania Efficacy Study.

BACKGROUND: Fortified blended foods (FBFs) are micronutrient-fortified food aid products containing cereals and pulses. It has been suggested to reformulate FBFs to include whey protein concentrate, use alternative commodities (e.g., sorghum and cowpea), and utilize processing methods such as extrusion to produce them. The Micronutrient Fortified Food Aid Pilot Project (MFFAPP) efficacy study was designed to test the efficacy of complementary feeding of newly formulated FBFs. OBJECTIVES: The aim of this study was to test the effectiveness of 5 newly formulated FBFs in combating iron deficiency anemia and vitamin A deficiency compared with traditionally prepared corn-soy blend plus (CSB+) and no intervention. A secondary aim was to determine the impact on underweight, stunting, wasting, and middle-upper arm circumference. METHODS: A 20-wk, partially randomized cluster study was completed. Two age groups (aged 6-23 and 24-53 mo) with hemoglobin status <10.3 g/dL, and weight-for-height z scores >-3 were enrolled and assigned to diet groups. Biochemical and anthropometric measurements were collected at 0, 10, and 20 wk. RESULTS: Both hemoglobin concentrations and anemia ORs were significantly improved in all intervention groups except for CSB+ and the no-intervention groups at week 20. Only extruded corn-soy blend 14 and the no-intervention age groups failed to significantly decrease vitamin A deficiency risk (P < 0.04). There were no consistent significant differences among groups in anthropometric outcomes. CONCLUSIONS: FBFs reformulated with sorghum, cowpea, corn, and soy significantly improved anemia and vitamin A deficiency ORs compared with week 0 and with no intervention. Although newly formulated FBFs did not significantly improve vitamin A deficiency or anemia compared with CSB+, CSB+ was the only FBF not to significantly improve these outcomes over the study duration. Our findings suggest that newly formulated sorghum- and cowpea-based FBFs are equally efficacious in improving these micronutrient outcomes. However, further FBF refinement is warranted. This trial was registered at clinicaltrials.gov as NCT02847962.

Novel Formulated Fortified Blended Foods Result in Improved Protein Efficiency and Hepatic Iron Concentrations Compared with Corn-Soy Blend Plus in Broiler Chickens.

BACKGROUND: Corn- and soybean-based fortified blended foods (FBFs) have been the primary food aid product provided by the United States. Sorghum and cowpea have been suggested as alternative FBF commodities because they are drought-tolerant, grown in food aid-receiving areas, and not genetically modified. Extrusion processing has also been suggested to improve the quality of these FBFs. OBJECTIVES: The aim of this study was to determine the protein quality and iron and vitamin A bioavailability of novel FBFs in broiler chickens. METHODS: Whey protein concentrate (WPC)-containing FBFs corn-soy blend 14, sorghum-soy, and sorghum-cowpea (SC); a soy protein isolate (SPI)-containing SC FBF (SC+SPI); 2 reformulated, overprocessed SC FBFs (O-SC+WPC, O-SC+SPI); and a nonextruded WPC-containing SC FBF were developed. Nonextruded corn-soy blend plus (CSB+), a currently used FBF, and a gamebird starter/grower diet were used as comparison diets. In the prepared FBF study, 9 groups of 8-d-old broiler chicks (n = 10) consumed prepared FBFs for 21 d. In the dry study, 8 groups of 4-d-old broiler chicks (n = 24; control: n = 23) consumed dry FBFs for 14 d. Results were analyzed by 1-factor ANOVA with least-significant-difference test. RESULTS: In the prepared study, novel formulated FBFs significantly increased caloric and protein efficiency and nonsignificantly increased body weight gain, despite similar food intake compared with CSB+. In the dry study, novel formulated FBFs, except for O-SC+SPI, significantly increased food intake, caloric efficiency, and protein efficiency and nonsignificantly increased body-weight gain compared with CSB+. Novel formulated FBFs nonsignificantly and significantly increased hepatic iron concentrations compared with all FBFs in the prepared and dry studies, respectively. CONCLUSION: Novel formulated FBFs, apart from O-SC+SPI, resulted in improved protein efficiencies and hepatic iron concentrations compared with CSB+, suggesting that they are of higher nutritional quality.

Bioavailable Iron and Vitamin A in Newly Formulated, Extruded Corn, Soybean, Sorghum, and Cowpea Fortified-Blended Foods in the In Vitro Digestion/Caco-2 Cell Model.

BACKGROUND: Fortified-blended foods (FBFs), particularly corn-soybean blend (CSB), are food aid products distributed in developing countries. The US Agency for International Development food aid quality review recommended developing extruded FBFs with the use of alternative commodities such as sorghum. OBJECTIVE: The objective of the study was to determine bioavailable iron and vitamin A content from newly developed extruded corn, soybean, sorghum, and cowpea FBFs compared with the nonextruded traditional food aid FBFs, corn-soy blend 13 (CSB13) and corn-soy blend plus (CSB+). METHODS: Eleven extruded FBFs-sorghum-cowpea (n = 7), sorghum-soy (n = 3), and corn-soy (n = 1)-along with 2 nonextruded FBFs-CSB13 and CSB+, and Cerelac (Nestlé), a commercially available fortified infant food, were prepared. Bioavailable iron and vitamin A contents were assessed by using the in vitro digestion/Caco-2 cell model. Dry FBFs, aqueous fractions, and Caco-2 cell pellet vitamin A contents were analyzed by HPLC. Dry FBF and aqueous fraction iron contents were measured by atomic absorptiometry, and bioavailable iron was assessed by measuring Caco-2 ferritin contents via ELISA. RESULTS: Iron and vitamin A concentrations in Cerelac and dry FBFs ranged from 8.0 to 31.8 mg/100 g and 0.3 to 1.67 mg/100 g, respectively. All of the extruded FBFs contained 4- to 7-fold significantly higher (P < 0.05) aqueous fraction iron concentrations compared with CSB13 and CSB+. However, there were no significant differences in Caco-2 cell ferritin and vitamin A concentrations between extruded FBFs, nonextruded FBFs, and or the basal salt solution negative control. CONCLUSION: Results support the theory that the consumption of newly developed extruded sorghum-cowpea, sorghum-soy, and corn-soy FBFs would result in iron and vitamin A concentrations comparable to traditional nonextruded CSB13 and CSB+ FBFs.

Salivary proline-rich protein may reduce tannin-iron chelation: a systematic narrative review.

BACKGROUND: Tannins are often cited for antinutritional effects, including chelation of non-heme iron. Despite this, studies exploring non-heme iron bioavailability inhibition with long-term consumption have reported mixed results. Salivary proline-rich proteins (PRPs) may mediate tannin-antinutritional effects on non-heme iron bioavailability. AIM: To review evidence regarding biochemical binding mechanisms and affinity states between PRPs and tannins, as well as effects of PRPs on non-heme iron bioavailability with tannin consumption in vivo. METHODS: Narrative systematic review and meta-analysis. Common themes in biochemical modeling and affinity studies were collated for summary and synthesis; data were extracted from in vivo experiments for meta-analysis. RESULTS: Thirty-two studies were included in analysis. Common themes that positively influenced tannin-PRP binding included specificity of tannin-PRP binding, PRP and tannin stereochemistry. Hydrolyzable tannins have different affinities than condensed tannins when binding to PRPs. In vivo, hepatic iron stores and non-heme iron absorption are not significantly affected by tannin consumption (d = -0.64-1.84; -2.7-0.13 respectively), and PRP expression may increase non-heme iron bioavailability with tannin consumption. CONCLUSIONS: In vitro modeling suggests that tannins favor PRP binding over iron chelation throughout digestion. Hydrolyzable tannins are not representative of tannin impact on non-heme iron bioavailability in food tannins because of their unique structural properties and PRP affinities. With tannin consumption, PRP production is increased, and may be an initial line of defense against tannin-non-heme iron chelation in vivo. More research is needed to compare competitive binding of tannin-PRP to tannin-non-heme iron complexes, and elucidate PRPs' role in adaption to non-heme iron bioavailability in vivo.

The impact of finasteride and dutasteride treatments on proliferation, apoptosis, androgen receptor, 5α-reductase 1 and 5α-reductase 2 in TRAMP mouse prostates.

BACKGROUND: Previously, we studied the effect of finasteride- or dutasteride-containing diets in male C57BL/6 TRAMP x FVB mice. Pre (6 weeks of age) and post (12 weeks of age) groups received finasteride or dutasteride to determine the efficacy of these pharmaceuticals on prostate cancer (PCa) development in male C57BL/6 TRAMP x FVB mice. Post-Dutasteride treatment was more effective than Pre-Dutasteride treatment, and dutasteride treatments were more effective than finasteride treatments in decreasing prostatic intraepithelial neoplasia (PIN) progression and PCa development. Finasteride and Pre-Dutasteride treatments significantly decreased high-grade PIN incidence, but increased poorly differentiated PCa incidence. In this study, molecular changes in prostates of these mice were characterized in an effort to elucidate the discordant response in Pre-Dutasteride and finasteride groups, and determine why Post-Dutasteride treatment was more effective. METHOD/PRINCIPAL FINDINGS: Ki-67 (proliferation marker) and androgen receptor (AR) protein, apoptotic DNA fragmentation (TUNEL assay), 5α-reductase 1 (5αR1) and 5α-reductase 2 (5αR2) mRNA were quantified in male TRAMP mice prostate tissues with genitourinary weight < 1 and > 1 gram. Overall, proliferation and AR were decreased and apoptosis was increased in most tumors versus prostate epithelium and hyperplasia. Proliferation and AR were increased notably in hyperplasia versus prostate epithelium and tumor. There were no clear trends or differences in 5α-reductase 1 and 5α-reductase 2 levels between large and small tumors. The discordant response in Pre-Finasteride and Pre-Dutasteride groups may be due to upregulated 5αR1 levels in large versus small tumors. It is not clear what the mechanism is for the different response in the Post-Finasteride group. Post-Dutasteride treatment was more effective than Pre-Dutasteride treatment in decreasing 5αR1 in large tumors. Therefore, this may be why this treatment was more effective in decreasing PIN progression and PCa development. CONCLUSION: The effect of finasteride and dutasteride on these biomarkers did not clearly elucidate their mechanism of action, but tumor 5αR1 levels were significantly positively correlated with adjusted prostate severe lesion score.

Newly formulated, protein quality-enhanced, extruded sorghum-, cowpea-, corn-, soya-, sugar- and oil-containing fortified-blended foods lead to adequate vitamin A and iron outcomes and improved growth compared with non-extruded CSB+ in rats.

Corn and soyabean micronutrient-fortified-blended foods (FBF) are commonly used for food aid. Sorghum and cowpeas have been suggested as alternative commodities because they are drought tolerant, can be grown in many localities, and are not genetically modified. Change in formulation of blends may improve protein quality, vitamin A and Fe availability of FBF. The primary objective of this study was to compare protein efficiency, Fe and vitamin A availability of newly formulated extruded sorghum-, cowpea-, soya- and corn-based FBF, along with a current, non-extruded United States Agency for International Development (USAID) corn and soya blend FBF (CSB+). A second objective was to compare protein efficiency of whey protein concentrate (WPC) and soya protein isolate (SPI) containing FBF to determine whether WPC inclusion improved outcomes. Eight groups of growing rats (n 10) consumed two white and one red sorghum-cowpea (WSC1 + WPC, WSC2 + WPC, RSC + WPC), white sorghum-soya (WSS + WPC) and corn-soya (CSB14 + WPC) extruded WPC-containing FBF, an extruded white sorghum-cowpea with SPI (WSC1 + SPI), non-extruded CSB+, and American Institute of Nutrition (AIN)-93G, a weanling rat diet, for 4 weeks. There were no significant differences in protein efficiency, Fe or vitamin A outcomes between WPC FBF groups. The CSB+ group consumed significantly less food, gained significantly less weight, and had significantly lower energy efficiency, protein efficiency and length, compared with all other groups. Compared with WSC1 + WPC, the WSC1 + SPI FBF group had significantly lower energy efficiency, protein efficiency and weight gain. These results suggest that a variety of commodities can be used in the formulation of FBF, and that newly formulated extruded FBF are of better nutritional quality than non-extruded CSB+.

5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores.

BACKGROUND: The contribution of 5α-reductase 1 and 5α-reductase 2 to prostate cancer development and progression is not clearly understood. TRAMP mice are a common prostate cancer model, in which 5α-reductase 1 and 5α-reductase 2 expression levels, along with prostate lesions scores, have not been investigated at different time points to further understand prostate carcinogenesis. METHOD/PRINCIPAL FINDINGS: To this end, 8-, 12-, 16-, and 20-week-old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion scores, 5α-reductase 1 and 5α-reductase 2 in situ hybridization expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry levels were measured. Levels of these markers were quantified in prostate epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12 and 16 weeks as the most severe lesion in all lobes. Moderately differentiated adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated carcinoma was not observed in any lobe until 12-weeks-old. 5α-reductase 1 and 5α-reductase 2 were not significantly decreased in tumors compared to prostate epithelium and hyperplasia in all groups, while proliferation, apoptosis, and androgen receptor were either notably or significantly decreased in tumors compared with prostate epithelium and hyperplasia in most or all groups. Prostate 5αR1 levels were positively correlated with adjusted prostate most severe lesion scores. CONCLUSION: Downregulation of androgen receptor and 5α-reductase 2, along with upregulation of 5α-reductase 1 in tumors may promote prostatic intraepithelial neoplasia and prostate cancer development in TRAMP mice.

Long-Term Dose-Response Condensed Tannin Supplementation Does Not Affect Iron Status or Bioavailability.

Background: Repeated phytic acid consumption leads to iron absorption adaptation but, to the best of our knowledge, the impact of repeated tannin consumption has not yet been established. Salivary proline-rich proteins (PRPs) may improve iron absorption by precipitating tannins. Objectives: This study aimed to determine the effect of long-term, dose-response condensed tannin supplementation on iron bioavailability and status and to assess the effect of salivary proteins on iron bioavailability during prolonged condensed tannin consumption. A secondary objective was to assess astringency as a potential marker for adaptation to tannins and iron bioavailability. Methods: Eleven nonanemic women were enrolled in a double-blind 3-dose crossover trial. Three (1.5, 0.25, or 0.03 g) condensed tannin supplements were consumed 3 times/d for 4 wk in random order, with 2-wk washouts in between. Meal challenges were employed before and after supplementation to assess iron bioavailability, iron status, salivary PRP changes, and astringency. Results: Tannin supplementation in any dose did not change iron bioavailability at any dose (P > 0.82) from weeks 0 to 4. Hemoglobin (P = 0.126) and serum ferritin (P = 0.83) were unchanged by tannin dose from weeks 0 to 4. There were significant correlations among tannin supplementation and iron bioavailability, basic proline-rich proteins (bPRPs) (r = 0.366, P = 0.003), and cystatin production (r = 0.27, P = 0.03). Astringency ratings did not change significantly within or between tannin doses (P > 0.126), but there were negative relations among bPRP (r < -0.32, P < 0.21), cystatin production (r < -0.2, P < 0.28), and astringency ratings. Conclusions: Condensed tannin consumption did not affect iron bioavailability or status regardless of the supplementation period in premenopausal nonanemic women. Correlation analyses suggest that bPRPs and cystatins are associated with improved iron bioavailability and that lower ratings of astringency may predict improved iron absorption with repeated tannin consumption.

The Impact of Tannin Consumption on Iron Bioavailability and Status: A Narrative Review.

Iron deficiency remains a global health issue, and antinutritional factors, such as tannins, are often cited as contributors to the high prevalence of deficiency. Despite this, tannin-rich diets may have potential beneficial cardiovascular and cancer-fighting properties because of the antioxidant activity of tannins. Furthermore, epidemiologic studies and long-term trials involving participants who consumed diets rich in antinutritional factors, particularly tannins, conflict with single-meal bioavailability studies. The purpose of this narrative review is to determine the effect of tannins on iron bioavailability and status and establish whether adaptation to tannins reduces the antinutritional effects of tannins over time. We also aimed to compare tannins used in iron studies. Common themes related to iron bioavailability and iron status with tannin consumption were collected and collated for summary and synthesis based on models and subjects used. Overall, there was dissonance between iron bioavailability and status in studies. Single-meal studies with hydrolyzable and oligomeric catechin and epicatechin tannins (tea and tannic acid) generally support reductions in bioavailability related to tannin consumption but not consumption of condensed tannin, which are more commonly found in food. Long-term animal model, epidemiologic, and multimeal studies generally do not support changes in iron status related to tannin intake. Studies suggest that long-term tannin consumption may impact iron status in a different manner than single-meal studies or bioavailability iron models predict. Furthermore, iron bioavailability studies that use condensed tannins, which are more commonly consumed, may better predict mealtime iron bioavailability. More research is needed to develop representative antinutritional iron studies and investigate mechanisms underlying the adaptation to tannins and other antinutritional factors that occur over time.

The MFFAPP Tanzania Efficacy Study Protocol: Newly Formulated, Extruded, Fortified Blended Foods for Food Aid.

Fortified blended foods (FBFs) are micronutrient-fortified blends of milled cereals and pulses that represent the most commonly distributed micronutrient-fortified food aid. FBFs have been criticized due to lack of efficacy in treating undernutrition, and it has also been suggested that alternative commodities, such as sorghum and cowpea, be investigated instead of corn and soybean. The Micronutrient Fortified Food Aid Pilot Project (MFFAPP) Tanzania efficacy study was the culmination of economic, processing, sensory, and nutrition FBF research and development. MFFAPP Tanzania was a 20-wk, partially randomized cluster design conducted between February and July 2016 that enrolled children aged 6-53 mo in the Mara region of Tanzania with weight-for-height z scores >-3 and hemoglobin concentrations <10.3 mg/dL. The intervention was complementary feeding of newly formulated, extruded FBFs (white sorghum cowpea variety 1, white sorghum-cowpea variety 2, red sorghum-cowpea, white sorghum-soy blend, and corn-soy blend 14) compared with Corn Soy Blend Plus (CSB+), a current US Agency for International Development-distributed corn-soy blend, and a no-FBF-receiving control. Screened participants (n = 2050) were stratified by age group (6-23 and 24-53 mo) and allocated to 1 of 7 FBF clusters provided biweekly. Biochemical and anthropometric data were measured every 10 wk at weeks 0, 10, and 20. The primary objectives of this study were to determine whether newly formulated, extruded corn-, soy-, sorghum-, and cowpea-based FBFs result in equivalent vitamin A or iron outcomes compared with CSB+. Changes in anthropometric outcomes were also examined. Results from the MFFAPP Tanzania Efficacy Study will inform food aid producers and distributers about whether extruded sorghum- and cowpea-based FBFs are viable options for improving the health of the undernourished. This trial was registered at clinicaltrials.gov as NCT02847962.

Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth.

Saw palmetto supplements (SPS) are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP) SPS ≥ 750 nM with testosterone significantly increased and ≥500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP) SPS ≥ 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP) SPS ≥ 750 nM or with androgens significantly decreased LNCaP cell number (n = 3; p < 0.05). Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n = 4), HLLP, HLHP, and HMLP SPS (n = 6) groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p < 0.05). Results may suggest that SPS inhibit 5α-reductase thereby preventing hamster flank organ growth.

Is the inclusion of animal source foods in fortified blended foods justified?

Fortified blended foods (FBF) are used for the prevention and treatment of moderate acute malnutrition (MAM) in nutritionally vulnerable individuals, particularly children. A recent review of FBF recommended the addition of animal source food (ASF) in the form of whey protein concentrate (WPC), especially to corn-soy blends. The justification for this recommendation includes the potential of ASF to increase length, weight, muscle mass accretion and recovery from wasting, as well as to improve protein quality and provide essential growth factors. Evidence was collected from the following four different types of studies: (1) epidemiological; (2) ASF versus no intervention or a low-calorie control; (3) ASF versus an isocaloric non-ASF; and (4) ASF versus an isocaloric, isonitrogenous non-ASF. Epidemiological studies consistently associated improved growth outcomes with ASF consumption; however, little evidence from isocaloric and isocaloric, isonitrogenous interventions was found to support the inclusion of meat or milk in FBF. Evidence suggests that whey may benefit muscle mass accretion, but not linear growth. Overall, little evidence supports the costly addition of WPC to FBFs. Further, randomized isocaloric, isonitrogenous ASF interventions with nutritionally vulnerable children are needed.

Preventive and therapeutic efficacy of finasteride and dutasteride in TRAMP mice.

BACKGROUND: The prostate cancer prevention trial (PCPT) and Reduction by dutasteride of Prostate Cancer Events (REDUCE) trial found that 5α-reductase (5αR) inhibitors finasteride and dutasteride respectively, decreased prostate cancer prevalence but also increased the incidence of high-grade tumors. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have high 5αR1 and low 5αR2 expression. Because finasteride inhibits only 5αR2, we hypothesized that it would not be as efficacious in preventing prostate cancer development and/or progression in C57BL/6 TRAMP x FVB mice as dutasteride, which inhibits both 5αR1 and 5αR2. METHOD/PRINCIPAL FINDINGS: Six-week-old C57BL/6 TRAMP x FVB male mice were randomized to AIN93G control or pre- and post- finasteride and dutasteride diet (83.3 mg drug/kg diet) groups (n =30-33) that began at 6 and 12 weeks of age, respectively, and were terminated at 20 weeks of age. The pre- and post- finasteride and dutasteride groups were designed to test the preventive and therapeutic efficacy of the drugs, respectively. Final body weights, genitourinary tract weights, and genitourinary tract weights as percentage of body weights were significantly decreased in the Pre- and Post-dutasteride groups compared with the control. The Post-dutasteride group showed the greatest inhibition of prostatic intraepithelial neoplasia progression and prostate cancer development. Surprisingly, the Post-dutasteride group showed improved outcomes compared with the Pre-dutasteride group, which had increased incidence of high-grade carcinoma as the most common and most severe lesions in a majority of prostate lobes. Consistent with our hypothesis, we found little benefit from the finasteride diets, and they increased the incidence of high-grade carcinoma. CONCLUSION: Our findings have commonalities with previously reported PCPT, REDUCE, and the Reduction by dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial results. Our results may support the therapeutic use of dutasteride, but not finasteride, for therapeutic or preventive use.

Fatty acid and phytosterol content of commercial saw palmetto supplements.

Saw palmetto supplements are one of the most commonly consumed supplements by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH and lower urinary tract symptoms (LUTS) with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fatty acids and phytosterols, of the saw palmetto supplements. To this end, we quantified the major fatty acids (laurate, myristate, palmitate, stearate, oleate, linoleate) and phytosterols (campesterol, stigmasterol, ß-sitosterol) in 20 commercially available saw palmetto supplements using GC-FID and GC-MS, respectively. Samples were classified into liquids, powders, dried berries, and tinctures. Liquid saw palmetto supplements contained significantly higher (p < 0.05) concentrations of total fatty acids (908.5 mg/g), individual fatty acids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Powders contained significantly higher (p < 0.05) concentrations of total fatty acids than tinctures, which contain negligible amounts of fatty acids (46.3 mg/g) and phytosterols (0.10 mg/g). Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement with the highest concentrations of both fatty acids and phytosterols.

The effect of finasteride and dutasteride on the growth of WPE1-NA22 prostate cancer xenografts in nude mice.

BACKGROUND: 5α-reductase 1 (5αR1) and 5α-reductase 2 (5αR2) convert testosterone into the more potent androgen dihydrotestosterone. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have increased 5αR1 and decreased 5αR2 expression. Previously, finasteride (5αR2 inhibitor) treatment begun 3 weeks post-tumor implantation had no effect on Dunning R3327-H rat prostate tumor growth. We believe the tumor compensated for finasteride treatment by increasing tumor 5αR1 expression or activity. We hypothesize that finasteride treatment would not significantly alter tumor growth even if begun before tumor implantation, whereas dutasteride (5αR1 and 5αR2 inhibitor) treatment would decrease tumor growth regardless of whether treatment was initiated before or after tumor implantation. METHODOLOGY/PRINCIPAL FINDINGS: Sixty 8-week-old male nude mice were randomized to Control, Pre- and Post-Finasteride, and Pre- and Post-Dutasteride (83.3 mg drug/kg diet) diet groups. Pre- and post-groups began their treatment diets 1-2 weeks prior to or 3 weeks after subcutaneous injection of 1×105 WPE1-NA22 human prostate cancer cells, respectively. Tumors were allowed to grow for 22 weeks; tumor areas, body weights, and food intakes were measured weekly. At study's conclusion, prostate and seminal vesicle weights were significantly decreased in all treatment groups versus the control; dutasteride intake significantly decreased seminal vesicle weights compared to finasteride intake. No differences were measured in final tumor areas or tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 prostate cancer cells and parent line RWPE-1 prostate epithelial cells were unaltered by treatment with testosterone, dihydrotestosterone, or mibolerone, suggesting that these cell lines are not androgen-sensitive. CONCLUSION: The lack of response of WPE1-NA22 prostate cancer cells to androgen treatment may explain the inadequate tumor growth observed. Additional studies are needed to determine whether finasteride and dutasteride are effective in decreasing prostate cancer development/growth.

Lycopene and apo-12'-lycopenal reduce cell proliferation and alter cell cycle progression in human prostate cancer cells.

Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8'-lycopenal, or apo-12'-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12'-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12'-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression.

Selenium, but not lycopene or vitamin E, decreases growth of transplantable dunning R3327-H rat prostate tumors.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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 were no significant interactions among nutrient combinations on tumor growth. Methylselenocysteine consumption also led to small, but significant decreases in body weight (P = 0.007), food intake (P = 0.012), and body weight gain/food intake ratio (P = 0.022). However, neither body weight nor gain/food intake ratio was correlated with tumor weight. Methylselenocysteine, lycopene, and gamma-tocopherol consumed alone and in combination did not alter serum testosterone or dihydrotestosterone concentrations; tumor proliferation or apoptosis rates. In addition, the diets also did not alter tumor or prostate androgen receptor, probasin, selenoprotein 15, selenoprotein P, or selenium binding protein 2 mRNA expression. However, using castration and finasteride-treated tissues from a previous study, we found that androgen ablation altered expression of these selenium-associated proteins. CONCLUSIONS: Of the three micronutrients tested, only methylselenocysteine consumption reduced growth of transplantable Dunning R3327-H prostate tumors, albeit through an unresolved mechanism.

Are the health attributes of lycopene related to its antioxidant function?

A variety of epidemiological trials have suggested that higher intake of lycopene-containing foods (primarily tomato products) or blood lycopene concentrations are associated with decreased cardiovascular disease and prostate cancer risk. Of the carotenoids tested, lycopene has been demonstrated to be the most potent in vitro antioxidant leading many researchers to conclude that the antioxidant properties of lycopene are responsible for disease prevention. In our review of human and animal trials with lycopene, or lycopene-containing extracts, there is limited support for the in vivo antioxidant function for lycopene. Moreover, tissue levels of lycopene appear to be too low to play a meaningful antioxidant role. We conclude that there is an overall shortage of supportive evidence for the "antioxidant hypothesis" as lycopene's major in vivo mechanism of action. Our laboratory has postulated that metabolic products of lycopene, the lycopenoids, may be responsible for some of lycopene's reported bioactivity.