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California strawberry consumption increased the abundance of gut microorganisms related to lean body weight, health and longevity in healthy subjects.
Ezzat-Zadeh, Z, Henning, SM, Yang, J, Woo, SL, Lee, RP, Huang, J, Thames, G, Gilbuena, I, Tseng, CH, Heber, D, et al
Nutrition research (New York, N.Y.). 2021;:60-70
Abstract
It was our hypothesis that foods high in polyphenols and fiber have prebiotic activity. This human intervention study aimed to determine if daily consumption of freeze-dried California strawberry powder (SBP) leads to changes in the intestinal microbiota, fecal cholesterol and bile acid (BA) microbial metabolites. Fifteen healthy adults consumed a beige diet+26 g of SBP for 4 weeks, followed by 2 weeks of beige diet only. Stool samples were collected at 0, 4, and 6 weeks. Fecal microbiota was analyzed by 16S rRNA sequencing; fecal cholesterol, BA, and microbial metabolites by gas chromatography. Confirming compliance, urine concentration of pelargonidin, urolithin A glucuronide and dimethylellagic acid glucuronide were present after 4 weeks of SBP consumption. Daily SBP altered the abundance of 24 operational taxonomic units (OTUs). Comparing week 4 to baseline the most significant increases were observed for one OTU from Firmicutes\Clostridia\ Christensenellaceae\NA, one OTU from Firmicutes\ Clostridia\Mogibacteriacea\NA, one OTU from Verrucomicrobia\ Verrucomicrobiaceae\Akkermansia\Muciniphila, one OTU from Actinobacteria\ Bifidobacteriaceae\Bifidobacterium\NA, and one OTU from Bacteroidetes\Bacteroidia\ Bacteroidaceae\Bacteroides and decrease of one OTU from Proteobacteria\ Betaproteobacteria\Alcaligenaceae\Sutterella. Comparing week 4 to 6, we observed a reversal of the same OTUs from C Christensenellaceae, V muciniphilia and C Mogibacteriaceae. Fecal short chain fatty acids and most of the fecal markers including cholesterol, coprostanol, primary and secondary BAs were not changed significantly except for lithocholic acid, which was increased significantly at week 6 compared to baseline. In summary, SBP consumption increased the abundance of gut microorganisms related to lean body weight, health and longevity, and increased fecal lithocholic acid at week 6 in healthy study participants.
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Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study.
Yang, J, Kurnia, P, Henning, SM, Lee, R, Huang, J, Garcia, MC, Surampudi, V, Heber, D, Li, Z
Nutrients. 2021;(11)
Abstract
Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equivalent of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metabolism in healthy adults. This study included a 4-week standardization to a low-polyphenol diet, followed by 4 weeks of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 weeks of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addition, there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body composition were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metabolism.
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A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer.
Pantuck, AJ, Pettaway, CA, Dreicer, R, Corman, J, Katz, A, Ho, A, Aronson, W, Clark, W, Simmons, G, Heber, D
Prostate cancer and prostatic diseases. 2015;(3):242-8
Abstract
BACKGROUND The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. METHODS Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. RESULTS One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). CONCLUSIONS Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.
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Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.
Li, Z, Henning, SM, Lee, RP, Lu, QY, Summanen, PH, Thames, G, Corbett, K, Downes, J, Tseng, CH, Finegold, SM, et al
Food & function. 2015;(8):2487-95
Abstract
The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.
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Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy.
Henning, SM, Wang, P, Said, JW, Huang, M, Grogan, T, Elashoff, D, Carpenter, CL, Heber, D, Aronson, WJ
The Prostate. 2015;(5):550-9
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Abstract
BACKGROUND Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. METHODS In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation (nuclear and cytoplasmic nuclear factor kappa B [NFκB]) and oxidation (8-hydroxydeoxy-guanosine [8OHdG]). Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. RESULTS Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFκB was significantly decreased in RP tissue of men consuming GT (P = 0.013) but not BT (P = 0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (P = 0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (P = 0.04). CONCLUSION Given the GT-induced changes in NFκB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis.
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Vitamin D receptor gene polymorphisms and prognosis of breast cancer among African-American and Hispanic women.
Mishra, DK, Wu, Y, Sarkissyan, M, Sarkissyan, S, Chen, Z, Shang, X, Ong, M, Heber, D, Koeffler, HP, Vadgama, JV
PloS one. 2013;(3):e57967
Abstract
BACKGROUND Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). Although African-Americans have the lowest levels of serum vitamin D, there is a dearth of information on VDR gene polymorphisms and breast cancer among African-Americans and Hispanics. This study examines whether VDR gene polymorphisms are associated with breast cancer in these cohorts. METHODS Blood was collected from 232 breast cancer patients (Cases) and 349 non-cancer subjects (Controls). Genotyping for four polymorphic variants of VDR (FokI, BsmI, TaqI and ApaI) was performed using the PCR-RFLP method. RESULTS An increased association of the VDR-Fok1 f allele with breast cancer was observed in African-Americans (OR = 1.9, p = 0.07). Furthermore, the FbTA, FbtA and fbtA haplotypes were associated with breast cancer among African-Americans (p<0.05). Latinas were more likely to have the VDR-ApaI alleles (Aa or aa) (p = 0.008). The VDR-ApaI aa genotype was significantly associated with poorly-differentiated breast tumors (p = 0.04) in combined Cases. Kaplan-Meier survival analysis showed decreased 5-year disease-free-survival (DFS) in breast cancer patients who had the VDR-Fok1 FF genotype (p<0.05). The Cox regression with multivariate analysis revealed the independent predictor value of the VDR-FokI polymorphism for DFS. The other three variants of VDR (BsmI, TaqI and ApaI) were not associated with disease outcome. CONCLUSIONS VDR haplotypes are associated with breast cancer in African-Americans, but not in Hispanic/Latinas. The VDR-FokI FF genotype is linked with poor prognosis in African-American women with breast cancer.
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Sibutramine plus meal replacement therapy for body weight loss and maintenance in obese patients.
Early, JL, Apovian, CM, Aronne, LJ, Fernstrom, MH, Frank, A, Greenway, FL, Heber, D, Kushner, RF, Cwik, KM, Walch, JK, et al
Obesity (Silver Spring, Md.). 2007;(6):1464-72
Abstract
OBJECTIVE Our objective was to assess the efficacy and safety of sibutramine with a low-calorie diet (LCD) and commercial meal-replacement product in achieving weight loss and weight-loss maintenance in obese patients. RESEARCH METHODS AND PROCEDURES Eight U.S. centers recruited 148 obese patients for a 3-month comprehensive weight-loss therapy (Phase I) comprising daily sibutramine 10 mg + LCD (two Slim-Fast meal-replacement shakes, one low-calorie meal; total kcal/d = 1200-1500). Patients (N = 113) who lost > or =5% of initial body weight during Phase I were randomized for a 9-month period (Phase II) to daily sibutramine 15 mg + LCD (one meal-replacement shake; two low-calorie meals: total kcal/d approximately 1200-1500) or daily placebo + three low-calorie meals (total kcal/d approximately 1200-1500). Both phases included behavior modification. Efficacy was assessed by body weight change during each phase and by the number of patients at endpoint maintaining > or =80% of the weight they had lost by the end of Phase I. Other outcomes included changes in cardiovascular and metabolic risk factors, adverse events, and vital signs. RESULTS Mean body weight change during Phase I was -8.3 kg (p < 0.001). Patients randomized to sibutramine in Phase II had an additional -2.5 kg mean weight loss vs. a 2.8-kg increase in the placebo group (p < 0.001). More sibutramine patients maintained > or =80% of their Phase I weight loss at the end of Phase II (85.5% vs. placebo 36.7%, p < 0.001). Most adverse events were mild or moderate in severity, and all serious adverse events were unrelated to sibutramine. DISCUSSION Sibutramine plus LCD with meal replacements and behavior modification is a safe and effective strategy for achieving and sustaining weight loss in obese patients.
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Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.
Pantuck, AJ, Leppert, JT, Zomorodian, N, Aronson, W, Hong, J, Barnard, RJ, Seeram, N, Liker, H, Wang, H, Elashoff, R, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;(13):4018-26
Abstract
PURPOSE Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy. EXPERIMENTAL DESIGN A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels. RESULTS The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption. CONCLUSIONS We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.
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Risk of prostate cancer in a randomized clinical trial of calcium supplementation.
Baron, JA, Beach, M, Wallace, K, Grau, MV, Sandler, RS, Mandel, JS, Heber, D, Greenberg, ER
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2005;(3):586-9
Abstract
BACKGROUND In some studies, high calcium intake has been associated with an increased risk of prostate cancer, but no randomized studies have investigated this issue. METHODS We randomly assigned 672 men to receive either 3 g of calcium carbonate (1,200 mg of calcium), or placebo, daily for 4 years in a colorectal adenoma chemoprevention trial. Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses. Subject reports were verified by medical record review. Serum samples, collected at randomization and after 4 years, were analyzed for 1,25-(OH)2 vitamin D, 25-(OH) vitamin D, and prostate-specific antigen (PSA). We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels. RESULTS After a mean follow-up of 10.3 years, there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [unadjusted rate ratio, 0.83; 95% confidence interval (95% CI), 0.52-1.32]. Most cases were not advanced; the mean Gleason's score was 6.2. During the first 6 years (until 2 years post-treatment), there were significantly fewer cases in the calcium group (unadjusted rate ratio, 0.52; 95% CI, 0.28-0.98). The calcium risk ratio for conversion to PSA >4.0 ng/mL was 0.63 (95% CI, 0.33-1.21). Baseline dietary calcium intake, plasma 1,25-(OH)2 vitamin D and 25-(OH) vitamin D levels were not materially associated with risk. CONCLUSION In this randomized controlled clinical trial, there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect.
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Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein.
Li, Z, Hong, K, Saltsman, P, DeShields, S, Bellman, M, Thames, G, Liu, Y, Wang, HJ, Elashoff, R, Heber, D
European journal of clinical nutrition. 2005;(3):411-8
Abstract
BACKGROUND Achieving significant weight loss and glycemic control in diabetic patients remains a challenging task. OBJECTIVE This study compared the effects of a soy-based meal replacement (MR) plan vs an individualized diet plan (IDP; as recommended by the American Diabetes Association) on weight loss and metabolic profile. DESIGN/SUBJECTS A total of 104 subjects were randomized prospectively to the two treatments for a total of 12 months. RESULTS In all, 77 of the 104 subjects completed the study. Percentage weight loss in MR group (4.57+/-0.81%) was significantly greater (P<0.05) than in IDP group (2.25+/-0.72%). Fasting plasma glucose was significantly reduced in MR group (126.4+/-4.9 mg/dl) compared with IDP group (152.5+/-6.6 mg/dl, P<0.0001) at 6 months but not at 12 months. Controlling for baseline levels, hemoglobin Alc level improved by 0.49+/-0.22% for those receiving MR when compared to IDP group (P<0.05). A greater number of subjects in MR group reduced their use of sulfonylureas (P<0.0001) and metformin (P<0.05) as compared to IDP group. High-sensitivity C-reactive protein (hs-CRP) decreased -26.3% (P = 0.019) in MR group compared to -7.06% (P = 0.338) in IDP group at 6 months. Similar changes were observed at 12 months with MR groups, with hs-CRP decreasing by -25.0% (P = 0.019) compared to -18.7% (P = 0.179) in IDP group. CONCLUSION This study demonstrates that MR is a viable strategy for weight reduction in diabetic patients, resulting in beneficial changes in measures of glycemic control and reduction of medications.