Identification of novel F2-isoprostane metabolites by specific UDP-glucuronosyltransferases.

UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the ß-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F2-IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F2t-IsoP and 5-epi-5-F2t-IsoP, two abundantly produced F2-IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F2-IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F2t-IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F2t-IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F2-IsoPs in human urine and showed that F2-IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F2-IsoP levels can be modified by factors other than redox mechanisms.

Ca:Mg ratio, medium-chain fatty acids, and the gut microbiome.

BACKGROUND & AIMS: Ketogenic medium-chain fatty acids (MCFAs) with profound health benefits are commonly found in dairy products, palm kernel oil and coconut oil. We hypothesize that magnesium (Mg) supplementation leads to enhanced gut microbial production of MCFAs and, in turn, increased circulating MCFAs levels. METHODS: We tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (NCT01105169), a double-blind 2 × 2 factorial randomized controlled trial enrolling 240 participants. Six 24-h dietary recalls were performed for all participants at the baseline and during the intervention period. Based on the baseline 24-h dietary recalls, the Mg treatment used a personalized dose of Mg supplementation that would reduce the calcium (Ca): Mg intake ratio to around 2.3. We measured plasma MCFAs, sugars, ketone bodies and tricarboxylic acid cycle (TCA cycle) metabolites using the Metabolon's global Precision Metabolomics™ LC-MS platform. Whole-genome shotgun metagenomics (WGS) sequencing was performed to assess microbiota in stool samples, rectal swabs, and rectal biopsies. RESULTS: Personalized Mg treatment (mean dose 205.58 mg/day with a range from 77.25 to 389.55 mg/day) significantly increased the plasma levels of C7:0, C8:0, and combined C7:0 and C8:0 by 18.45%, 25.28%, and 24.20%, respectively, compared to 14.15%, 10.12%, and 12.62% decreases in the placebo arm. The effects remain significant after adjusting for age, sex, race and baseline level (P = 0.0126, P = 0.0162, and P = 0.0031, respectively) and FDR correction at 0.05 (q = 0.0324 for both C7:0 and C8:0). Mg treatment significantly reduced the plasma level of sucrose compared to the placebo arm (P = 0.0036 for multivariable-adjusted and P = 0.0216 for additional FDR correction model) whereas alterations in daily intakes of sucrose, fructose, glucose, maltose and C8:0 from baseline to the end of trial did not differ between two arms. Mediation analysis showed that combined C7:0 and C8:0 partially mediated the effects of Mg treatment on total and individual ketone bodies (P for indirect effect = 0.0045, 0.0043, and 0.03, respectively). The changes in plasma levels of C7:0 and C8:0 were significantly and positively correlated with the alterations in stool microbiome α diversity (r = 0.51, p = 0.0023 and r = 0.34, p = 0.0497, respectively) as well as in stool abundance for the signatures of MCFAs-related microbiota with acyl-ACP thioesterase gene producing C7:0 (r = 0.46, p = 0.0067) and C8:0 (r = 0.49, p = 0.003), respectively, following Mg treatment. CONCLUSIONS: Optimizing Ca:Mg intake ratios to around 2.3 through 12-week personalized Mg supplementation leads to increased circulating levels of MCFAs (i.e. C7:0 and C8:0), which is attributed to enhanced production from gut microbial fermentation and, maybe, sucrose consumption.

The Fish Oil to Reduce Tobacco Use iN Expectant mothers (FORTUNE) feasibility trial.

BACKGROUND: Three small clinical trials have suggested that supplementation with n-3 long-chain polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) found in fish oils may reduce nicotine cravings and at higher doses reduce cigarette consumption. Pregnant women who smoke have fewer pharmacologic options to aid them with smoking cessation. Although n-3 long-chain polyunsaturated fatty acid supplementation has been studied in pregnancy, few studies have evaluated doses of ≥4 g per day, and no previous studies have selectively enrolled pregnant women who smoke. High-dose n-3 long-chain polyunsaturated fatty acids may aid cessation but could be poorly tolerated in pregnant women who smoke because of gastrointestinal side effects. OBJECTIVE: We conducted a feasibility trial to determine the tolerability of high-dose n-3 long-chain polyunsaturated fatty acid supplementation in pregnant women who smoked. We hypothesized that n-3 long-chain polyunsaturated fatty acid doses of 4.2 g a day would be well-tolerated relative to an olive oil placebo. We assessed red blood cell phospholipid membrane concentrations at baseline and end of therapy (4 weeks) and piloted outcomes for a future efficacy trial of n-3 long-chain polyunsaturated fatty acid supplementation for smoking cessation in pregnancy. STUDY DESIGN: We recruited 28 pregnant women between the gestational ages of 6 and 36 weeks who reported daily cigarette smoking and were motivated to quit to participate in a double-blind placebo-controlled randomized feasibility trial of 4.2 g per day of n-3 long-chain polyunsaturated fatty acid supplementation. Participants reported cigarettes per day, completed the Fagerström Test for Cigarette Dependence, and provided blood, urine, and exhaled CO samples. We used repeated-measures analysis of variance to pilot analyses of changes in cigarettes per day and Fagerström Test for Cigarette Dependence scores. RESULTS: At baseline, red blood cell membrane eicosapentaenoic acid concentrations were negatively correlated with cigarettes per day (r=-0.44; P=.04). By 4 weeks, circulating n-3 long-chain polyunsaturated fatty acid levels increased by 18% in the n-3 long-chain polyunsaturated fatty acid supplementation arm vs a decrease of 3% in the placebo arm. Occurrence of gastrointestinal side effects such as burping, heartburn, diarrhea, abdominal pain, or nausea did not differ statistically between study arms. At 4 weeks, participants allocated to the n-3 long-chain polyunsaturated fatty acids arm reported a median of 3 cigarettes per day (interquartile range, 1-8) vs 7 cigarettes per day (interquartile range, 1-14) in the placebo arm, which was not statistically significant (P=.99). Participants allocated to the n-3 long-chain polyunsaturated fatty acids arm had a decrease of 1 (interquartile range, 0-1) on the Fagerström Test for Cigarette Dependence score vs 0 (interquartile range, 0-0) for placebo (P=.46). CONCLUSION: High-dose n-3 long-chain polyunsaturated fatty acids may be tolerated in pregnant women who smoke; however, there was a high level of participant dropout, with more participants allocated to the fish oil arm becoming lost to follow-up. These results will inform the design of a future large-scale randomized controlled trial to test the impact of fish oil supplements on smoking cessation in pregnancy.

N-3 Long Chain Fatty Acids Supplementation, Fatty Acids Desaturase Activity, and Colorectal Cancer Risk: A Randomized Controlled Trial.

INTRODUCTION: n-3 long-chain polyunsaturated fatty acids (LCPUFA) have anti-inflammatory effects and may reduce colorectal cancer risk. The purpose of this study was to evaluate the effects of n-3 LCPUFA supplementation on markers of rectal cell proliferation and apoptosis and examine how genetic variation in desaturase enzymes might modify this effect. METHODS: We conducted a randomized, double-blind, control six-month trial of 2.5 grams of n-3 LCPUFA per day compared to olive oil. Study participants had a history of colorectal adenomas. Randomization was stratified based on the gene variant rs174535 in the fatty acid desaturase 1 enzyme (FADS1). Our primary outcome was change in markers of rectal epithelial proliferation and apoptosis. RESULTS: A total of 141 subjects were randomized. We found no difference in apoptosis markers between participants randomized to n-3 LCPUFA compared to olive oil (P = 0.41). N-3 LCPUFA supplementation increased cell proliferation in the lower colonic crypt compared to olive oil (P = 0.03) however baseline indexes of proliferation were different between the groups at randomization. We found no evidence that genotype modified the effect. CONCLUSIONS: Our study did not show evidence of a proliferative or pro-apoptotic effect on n-3 LCPUFA supplementation on rectal mucosa regardless of the FADS genotype.ClinicalTrials.gov Identifier: NCT01661764Supplemental data for this article is available online at https://dx.doi.org/10.1080/01635581.2021.1955286.

Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS): study protocol for a double-blind, randomized, placebo-controlled parallel clinical trial of n-3 polyunsaturated fatty acids in pregnant smokers.

BACKGROUND: Tobacco use during pregnancy is the most important modifiable risk factor associated with adverse pregnancy outcomes, increasing the risk of preterm birth, intrauterine growth restriction and sudden infant death syndrome. Fewer than half of pregnant smokers can quit on their own. Identifying safe and effective therapies to prevent tobacco-related adverse pregnancy outcomes and/or increase smoking cessation in pregnant women would have a substantial public health impact. Cigarette smoking is associated with a relative deficiency in circulating n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) levels. A recent analysis found that smokers taking n-3 LCPUFAs during pregnancy had a reduction in preterm labor risk when compared to non-smokers. Studies have shown that supplemental n-3 LCPUFAs may also reduce nicotine cravings and daily cigarette use. Thus, smokers may benefit from supplemental n-3 LCPUFAs by lowering the risk of preterm labor and/or increased smoking cessation. To address important remaining knowledge gaps, we propose the Investigating N-3 Fatty Acids to prevent Neonatal Tobacco related outcomeS (INFANTS). METHODS: The INFANTS study is a multicenter, randomized, double-blind, placebo-controlled study that will randomize 400 pregnant smokers to either supplemental n-3 LCPUFAs or placebo. Participants will be enrolled between 12 and 24 weeks' gestation and followed until 6 weeks after delivery. We will recruit from clinical centers throughout Middle Tennessee. We will assess smoking behavior after 12 weeks of supplementation using self-report and validated biomarkers of tobacco exposure. We will measure response to supplementation using biological markers of n-3 LCPUFA status. Our primary endpoint will be preterm labor as reflected by gestational age at delivery. Our secondary endpoint will be change from baseline in cigarettes per day at 12 weeks. DISCUSSION: This study tests the hypothesis that smoking-induced n-3 LCPUFA deficiencies contribute to tobacco-related adverse pregnancy outcomes and that supplementation of n-3 LCPUFAs in pregnant smokers may prevent these complications. If our study demonstrates that supplemental n-3 LCPUFAs are effective at reducing the risk of tobacco-related adverse neonatal outcomes and/or reducing tobacco use during pregnancy, our results could have an immediate and major impact on pregnancy care and neonatal outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04417595. Registered on April 21, 2020.

Evaluation of determinants for age disparities in the survival improvement of colon cancer: results from a cohort of more than 486,000 patients in the United States.

Over the past two decades, elderly colon cancer patients experienced less improvement in survival than their younger counterparts, yet the contributing factors remain unknown. We aimed to evaluate factors that may contribute to the age disparity of survival improvement among patients with colon cancer. Using data from the National Cancer Database, we identified patients diagnosed with colon cancer between 2004 and 2012 with follow-up data up to 2017. The hazard ratios (HR) and 95% confidence intervals (CI) for 5-year OS associated with study variables were estimated using multivariable Cox regression. Among 486,284 patients included in this study, elderly patients (aged ≥75) had a lower adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines (% of non-adherence: 45.3%) than younger patients (aged <50, 19.3%; P<0.001). After adjusting for demographics, access to care and clinical characteristics, compared with patients diagnosed between 2004 and 2006, younger and older patients diagnosed between 2010 and 2012 experienced 16% (HR: 0.84, 95% CI: 0.81-0.88) and 6% (HR: 0.94, 95% CI: 0.93-0.95) reductions in mortality (P for interaction=1.42×10-5), respectively. After an additional adjustment for guideline adherence status, no significant difference in the improvement of survival was noted (P for interaction=0.17). The association patterns were similar regardless of tumor stage, race, and high comorbidity scores (all P for interaction>0.05). Several patient-related factors were identified in association with noncompliance to NCCN guidelines, including comorbidity status. However, over 60% of noncompliance elderly patients had a Charlson comorbidity score of 0. The observed age disparity in survival improvement among colon cancer patients was primarily explained by a slower improvement in adherence to NCCN treatment guidelines in elderly than younger patients. Many older adults were not receiving recommended therapies despite minimal comorbidities. Our findings call for measures to increase adherence to treatment guidelines among elderly patients to improve survival.

Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.

BACKGROUND: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. METHODS: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. RESULTS: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. CONCLUSIONS: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. IMPACT: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial.

BACKGROUND: Deterioration of ionized calcium (Ca2+) handling in neurons could lead to neurodegenerative disease. Magnesium (Mg) antagonizes Ca during many physiologic activities, including energy metabolism and catalyzation of demethylation from 5-methylcytosine(5-mC) to 5-hydroxymethylcytosine(5-hmC). OBJECTIVE: To test the hypothesis that actively reducing the Ca:Mg intake ratio in the diet through Mg supplementation improves cognitive function, and to test whether this effect is partially mediated by modified cytosines in Apolipoprotein E (APOE). METHODS: This study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized. RESULTS: Among those aged > 65 years old who consumed a high Ca:Mg ratio diet, we found that reducing the Ca:Mg ratio to around 2.3 by personalized Mg supplementation significantly improved cognitive function by 9.1% (p = 0.03). We also found that reducing the Ca:Mg ratio significantly reduced 5-mC at the cg13496662 and cg06750524 sites only among those aged > 65 years old (p values = 0.02 and 0.03, respectively). Furthermore, the beneficial effect of reducing the Ca:Mg ratio on cognitive function in those aged over 65 years was partially mediated by reductions in 5-mC levels (i.e., cg13496662 and cg06750524) in APOE (p for indirect effect = 0.05). CONCLUSION: Our findings suggest that, among those age 65 and over with a high dietary Ca:Mg ratio, optimal Mg status may improve cognitive function partially through modifications in APOE methylation. These findings, if confirmed, have significant implications for the prevention of cognitive aging and Alzheimer's disease.Clinical Trial Registry number and website: #100106 https://clinicaltrials.gov/ct2/show/NCT03265483.

Effects of fish oil supplementation on eicosanoid production in patients at higher risk for colorectal cancer.

Fish oil supplementation may represent a potential chemopreventive agent for reducing colorectal cancer risk. The mechanism of action of fish oil is unknown but presumed to be related to eicosanoid modification. The purpose of this study was to evaluate the effects of fish oil supplementation on the levels of urinary and rectal eicosanoids. We conducted a randomized, double-blind, controlled trial of 2.5 g of fish oil per day compared with olive oil supplementation over a 6-month period. Study participants had a history of colorectal adenomas. Randomization was stratified based on the gene variant rs174535 in the fatty acid desaturase 1 enzyme (FADS1), which affects tissue levels of arachidonic acid. A total of 141 participants were randomized. Urinary prostaglandin E2 metabolite (PGE-M) was measured at baseline, 3, and 6 months and rectal prostaglandin E2 (PGE2) at baseline and 6 months. Repeated-measures linear regression was used to determine the effect of the intervention on each outcome measure. Overall, fish oil supplementation was found to reduce urinary PGE-M production compared with olive oil (P=0.03). Fish oil did not reduce rectal PGE2 overall; however, it did significantly reduce PGE2 in the subgroup of participants not using aspirin or NSAIDs (P=0.04). FADS1 genotype did not seem to modify effects of fish oil on PGE2 production. We conclude that fish oil supplementation has a modest but beneficial effect on eicosanoids associated with colorectal carcinogenesis, particularly in those not taking aspirin or NSAIDs.

Dietary intake of PUFAs and colorectal polyp risk.

BACKGROUND: Marine-derived n-3 (omega-3) PUFAs may reduce risk of developing colorectal cancer; however, few studies have investigated the association of n-3 PUFA intakes on colorectal polyp risk. OBJECTIVE: The objective of this study was to examine the associations of dietary PUFA intake on risk of colorectal adenomatous and hyperplastic polyps. DESIGN: This was a colonoscopy-based case-control study that included 3166 polyp-free control subjects, 1597 adenomatous polyp cases, and 544 hyperplastic polyp cases. Dietary PUFA intake was calculated from food-frequency questionnaires and tested for association by using unconditional logistic regression. The urinary prostaglandin E(2) metabolite, which is a biomarker of prostaglandin E(2) production, was measured in 896 participants by using liquid chromatography and tandem mass spectrometry. RESULTS: n-6 PUFAs were not associated with adenomatous or hyperplastic polyps in either men or women. Marine-derived n-3 PUFAs were associated with reduced risk of colorectal adenomas in women only, with an adjusted OR of 0.67 (95% CI: 0.47, 0.97) for the highest quintile of intake compared with the lowest quintile of intake (P-trend = 0.01). Dietary intake of α-linolenic acid was associated with an increased risk of hyperplastic polyps in men (P-trend = 0.03), which was not seen in women. In women, but not in men, dietary intake of marine-derived n-3 PUFAs was negatively correlated with urinary prostaglandin E(2) production (r = -0.18; P = 0.002). CONCLUSION: Higher intakes of marine-derived n-3 PUFAs are associated with lower risk of adenomatous polyps in women, and the association may be mediated in part through a reduction in the production of prostaglandin E(2). This trial was registered at clinicaltrials.gov as NCT00625066.

Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: a prospective cohort study.

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFAs) and the ratio of n-6 PUFAs to marine-derived n-3 PUFAs with breast cancer risk in the Shanghai Women's Health Study, a prospective cohort study including 72,571 cancer-free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person-years of follow-up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α-linolenic acid or marine-derived n-3 PUFA. We found a statistically significant interaction between n-6 PUFA intake, marine-derived n-3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine-derived n-3 PUFA and higher intake (the highest tertile) of n-6 PUFA had an increase risk for breast cancer (RR = 2.06; 95% CI = 1.27-3.34) compared to women with higher intake (the highest tertile) of marine-derived n-3 PUFAs and lower intake (the lowest tertile) of n-6 PUFAs after adjusting for potential confounders. The relative amounts of n-6 PUFA to marine-derived n-3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids.

The association of plasma fatty acids with prostate cancer risk in African Americans and Africans.

Higher risk for prostate cancer (PCa) among African Americans is partly associated with exposure to dietary fatty-acids, the carcinogenic effects of which remain controversial. Odds ratio of PCa risk was determined by unconditional logistic regression comparing highest with lowest quartiles of plasma fatty-acids in a case-control design. Mean age for 173 African Americans and 340 Nigerians was 56.9 +/- 9.8 and 60.1 +/- 14.0, p<.006, median (25th, 75th percentile) plasma fatty-acid was 2598 (2306, 3035) microg/ml and 2420 (2064, 2795) microg/ml, p<.001, with 48 (27.7%) and 66 (19.4%) PCa cases, respectively. African Americans recorded higher total, omega-6, and trans, but lower saturated and omega-3 fatty-acids, with non-significant PCa risk association for total, omega-6 and trans fatty acids. Positive PCa risk trend was observed in both populations with nervonic, erucic, and arachidonic acids, with docosahexaenoic acid (DHA) among African Americans, and with behenic and stearic acids in Nigerians. Non-significant negative PCa risk trend was observed with ecosapentaenoic acid (EPA) in Nigerians only. These preliminary findings need to be further explored in a larger study that will include risk analysis of fatty-acid ratios to clarify their combined impact on PCa risk.

Race and socioeconomic status are independently associated with benign prostatic hyperplasia.

PURPOSE: Prostate enlargement is common as men age. However, differences in the diagnosis or treatment of clinical benign prostatic hyperplasia between black and white men remain poorly understood. We investigated racial differences in and surgical intervention for benign prostatic hyperplasia in a large and predominantly low income population. MATERIALS AND METHODS: Participants included 21,949 men, of whom 79.8% were black and 20.2% were white, recruited from 60 community health centers in the southeastern United States between 2002 and 2007. Benign prostatic hyperplasia, surgical intervention for benign prostatic hyperplasia, and economic and demographic indexes, eg education, household income, health insurance and marital status, were determined by an interview in person. Logistic regression was used to summarize the association between race and benign prostatic hyperplasia while controlling for health care access and socioeconomic status. RESULTS: Black men were approximately half as likely to report a benign prostatic hyperplasia diagnosis compared to white men (4.1% vs 9.9%, age adjusted OR 0.45, 95% CI 0.40, 0.51), a difference that persisted with only small abatement after controlling for age, income, insurance coverage, comorbidity, education and other factors (adjusted OR 0.49, 95% CI 0.43, 0.56)). Of men with benign prostatic hyperplasia surgical intervention for that condition (133 patients) was more prevalent in black vs white men (12.9% vs 9.1%, adjusted OR 1.65, 95% CI 1.10, 2.48). CONCLUSIONS: After controlling for economic factors associated with benign prostatic hyperplasia black men were significantly less likely to report a prior benign prostatic hyperplasia diagnosis. In contrast, surgical intervention typically reserved for severe benign prostatic hyperplasia was more common in black men. Our results suggest that race and socioeconomic status are independently associated with benign prostatic hyperplasia.