Intake of supplemental and total fiber and risk of colorectal adenoma recurrence in the wheat bran fiber trial.

The Wheat Bran Fiber (WBF) trial was a double-blind Phase III clinical trial in which participants were randomized to a cereal fiber supplement of either 13.5 or 2.0 g/day. No protective effect for adenoma recurrence was observed for those randomized to the high-fiber group as compared with those in the low-fiber group. However, the high-fiber group had significantly lower adherence to the supplement as assessed by cereal box counts. The aim of this study was to determine whether reported supplemental and total fiber intake affected colorectal adenoma recurrence in the WBF trial population, regardless of treatment group assignment. A total of 1208 participants who completed the WBF trial had a colonoscopy before the date of the last cereal box count and/or at least one colonoscopy within 90 days after it and, thus, were eligible for the current analyses. Statistical analyses were done using multivariate logistic regression models that included potentially confounding variables. Compared with individuals consuming less than 1.8 g/day of supplemental fiber, the adjusted odds ratio (95% confidence interval) for adenoma recurrence for those consuming greater than 11.0 g/day was 0.94 (0.66-1.33). The odds ratio (95% confidence interval) for participants whose total fiber intake was greater than 30.3 g/day was 0.98 (0.68-1.42) compared with those whose intake was less than 17.9 g/day. The results of this study show that neither fiber intake from a wheat bran supplement nor total fiber intake affects the recurrence of colorectal adenomas, thus lending further evidence to the body of literature indicating that consumption of a high-fiber diet, especially one rich in cereal fiber, does not reduce the risk of colorectal adenoma recurrence.     

Baseline dietary fiber intake and colorectal adenoma recurrence in the wheat bran fiber randomized trial

BACKGROUND: The Wheat Bran Fiber (WBF) trial was a double-blind, high-fiber versus low-fiber phase III intervention trial in which participants were randomly assigned to receive a cereal fiber supplement of either 2.0 g/day or 13.5 g/day to assess whether a high-fiber supplement could decrease risk of recurrent colorectal adenomas. Although no effect of the supplement on polyp recurrence was observed, participants consumed a baseline average of 17.5 grams of fiber per day, which may have been sufficient to protect against adenoma recurrence. Therefore, we examined whether baseline fiber intake affected colorectal adenoma recurrence or modified the effect of treatment group in the WBF trial participants. METHODS: Quartiles of baseline fiber intake were calculated on the basis of the distribution in the study population. Odds ratios (ORs) for adenoma recurrence were calculated using the lowest quartile of fiber intake as the reference. The effect of fiber from specific food sources on adenoma recurrence was also assessed. All statistical tests were two-sided. RESULTS: Adjusted ORs (95% confidence intervals) for adenoma recurrence were 0.79 (0.56 to 1.12), 0.76 (0.54 to 1.08), and 0.83 (0.57 to 1.19) for the second, third, and fourth quartiles, respectively. Fiber from the three primary food sources (fruits; breads, cereals and crackers; and vegetables) had no appreciable effect on adenoma recurrence. Baseline fiber intake also had little effect on adenoma recurrence when the population was stratified by treatment group. In addition, there was no interaction between treatment group and quartile of baseline fiber intake. CONCLUSIONS: No association was found between amount of fiber consumed at baseline and adenoma recurrence in the WBF trial participants. The baseline fiber intake, whether considered as a whole or from specific sources, did not modify the effect of treatment group.     

Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients

There has been concern that long-term supplementation with high-dose antioxidant vitamins, especially vitamin E (alpha-tocopherol), may increase all-cause mortality. We conducted a randomized controlled trial with alpha-tocopherol (400 IU/day) and beta-carotene (30 mg/day) supplements among 540 head and neck cancer patients treated by radiation therapy. Supplementation with beta-carotene was discontinued during the trial. The supplements were given during radiation therapy and for 3 additional years. During the follow-up (median 6.5 years), 179 deaths were recorded. All death certificates were obtained. All-cause and cause-specific mortality rates were compared between the 2 arms of the trial by Cox regression. All-cause mortality was significantly increased in the supplement arm: hazard ratio: 1.38, 95% confidence interval 1.03-1.85. Cause-specific mortality rates tended to be higher in the supplement arm than in the placebo arm. Our results concur with previous reports to suggest that high-dose vitamin E could be harmful.     

The effect of a low-fat,high fiber,fruit and vegetable intervention on rectal mucosal proliferation

BACKGROUND: Because studies of diet and colorectal carcinoma tend to be large and complex, researchers have long been interested in the investigation of dietary exposures in relation to putative intermediate markers of large bowel malignancy, such as colorectal epithelial cell proliferation. The basic hypothesis underlying these investigations is that specific dietary components may reduce or increase the rate of cell proliferation, which, in turn, may reduce or increase neoplastic changes in the large bowel. METHODS: The authors assessed the effects of a 4-year, low-fat, high-fiber, fruit and vegetable-enriched dietary intervention on colorectal epithelial cell proliferation among 399 participants from the Polyp Prevention Trial, a randomized multicenter trial with adenoma recurrence as the primary endpoint. Rectal biopsies were taken from flat, normal appearing mucosa on patients at baseline, after 1 year, and after 4 years. Two assays, bromodeoxyuridine (Brd U) and proliferating cell nuclear antigen (PCNA), were used to evaluate two summary measures of proliferation: the labeling index (LI) and the proliferative height (PH). RESULTS: There were no significant differences between changes in LI and PH over the 4-year period for the intervention and control groups. This finding parallels the finding in the larger primary study, in which the dietary intervention did not alter adenoma recurrence rates. CONCLUSIONS: A low-fat, high-fiber, fruit and vegetable-enriched dietary intervention did not alter rectal mucosal cell proliferation rates.     

Vitamin supplement use and risk for breast cancer: the Shanghai Breast Cancer Study

Objective The influence of vitamin supplements on breast cancer risk is unclear and the interactive effects of dietary and supplemental sources are unknown. This study investigated (1) the association between self-reported vitamin supplement use (multivitamin, A, B, C, and E) and breast cancer and (2) the combined effect of vitamin supplements in relation to dietary vitamin intakes on breast cancer risk. Methods The Shanghai Breast Cancer Study was a population-based case-control study conducted in Shanghai in 1996-1998 (Phase I) and 2002-2004 (Phase II). Participants were aged 25-64 (Phase I) and 20-70 years (Phase II). The analyses included 3,454 incident breast cancer cases and 3,474 controls. Unconditional logistic regression models were used to determine adjusted odds ratios (ORs) for breast cancer risk associated with vitamin supplement use. Results Overall, breast cancer risk was not related to any vitamin supplement intake. However, a 20% reduction in breast cancer risk was observed with vitamin E supplement use among women with low-dietary vitamin E intake (OR = 0.8; 95% confidence interval (CI), 0.6-1.0). A non-significant 20% risk reduction was observed among vitamin B supplement users with low B dietary intake (OR = 0.8; 95% CI, 0.6-1.1). Frequent use of a vitamin B supplement was adversely associated with breast cancer risk among those with high dietary vitamin B intake (OR = 1.4; 95% CI: 0.9-2.1; P for interaction = 0.07). Conclusions This study suggests that vitamins E and B supplements may confer protection against breast cancer among women who have low dietary intake of those vitamins.     

Dietary supplement use and colorectal cancer risk: A systematic review and meta‐analyses of prospective cohort studies

Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta‐analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up to January 2013. Original and peer‐reviewed papers on dietary supplement use and colorectal cancer, colon cancer, or rectal cancer incidence were included. “Use‐no use”(U‐NU), “highest‐lowest”(H‐L) and “dose‐response”(DR) meta‐analyses were performed. Random‐effects models were used to estimate summary estimates. In total, 24 papers were included in the meta‐analyses. We observed inverse associations for colorectal cancer risk and multivitamin (U‐NU: RR = 0.92; 95% CI: 0.87,0.97) and calcium supplements (U‐NU: RR = 0.86; 95% CI: 0.79,0.95; H‐L: RR = 0.80; 95% CI: 0.70,0.92; DR: for an increase of 100 mg/day, RR = 0.96; 95% CI: 0.94,0.99). Inconsistent associations were found for colon cancer risk and supplemental vitamin A and vitamin C, and for colorectal cancer risk and supplemental vitamin D, vitamin E, garlic and folic acid. Meta‐analyses of observational studies suggest a beneficial role for multivitamins and calcium supplements on colorectal cancer risk, while the association with other supplements and colorectal cancer risk is inconsistent. Residual confounding of lifestyle factors might be present. Before recommendations can be made, an extensive assessment of dietary supplement use and a better understanding of underlying mechanisms is needed.     

Use of vitamins, minerals, and nutritional supplements by participants in a chemoprevention trial

BACKGROUND: The growing use of vitamins, minerals, and nutritional supplements has the potential to influence the design and interpretation of randomized controlled trials of chemopreventive agents. To the extent that these complementary agents are effective, they could limit the ability of trials to demonstrate an effect of the agents under study. METHODS: During the course of a colorectal neoplasia chemoprevention trial using aspirin in a group of colorectal carcinoma survivors, the authors obtained information on the use of vitamins, minerals, and supplements at baseline and every 6 months. The information from 622 study participants was categorized and enumerated. RESULTS: One or more supplements were used at some time by 341 (55%) subjects. Among those who took supplements, 66% took more than 1 and 13% took 5 or more. The mean number of supplements taken was 2.6 (1.7 standard deviation). Vitamins were the most commonly used (49%), followed by minerals (22%), botanicals (13%), and others (5%). Among the vitamins, the most frequently used were multivitamins (38% of subjects), vitamin C (18%), and vitamin E (22%). Calcium (16%) was the most frequent mineral. Among users, there were no differences in supplement use by age or gender. CONCLUSIONS: Supplement use was common among colorectal carcinoma survivors enrolled in a prevention trial. Investigators should record the information on supplement use so that the possible impact of the supplements on trial endpoints can be evaluated. It may be necessary to increase the size of studies if many of the subjects take potentially effective supplements.     

Large bowel cancer: prospects for control

The incidence of large bowel cancer, a major cancer in the western world, varies significantly for different segments of the colon as a function of geographic pathology, but the rectal cancer incidence shows smaller distinctions in different countries. Cancer in the descending and sigmoid colon relate to western lifestyle, particularly the high level of dietary fat (40-45% of calories). The lower risk seen in Finland is associated with a high intake of cereal fibers. The current information base with regard to the nutritional factors that show an enhancing effect by high-fat intake and protective effects of agents increasing stool bulk, such as cereal and vegetable fibers, is sufficiently convincing to allow recommendations for intervention trials using fat and fiber. Optimal levels for disease prevention are different from normally accepted and traditional intakes of fat and fiber, and measurable parameters such as serum cholesterol levels, stool weight, fecal bile acid concentration, and perhaps fecal mutagens reflect averages derived from the intake of a high-fat, low-fiber diet that are not optimal. Optimal recommendations are for a dietary level of 20-25% of fat calories and about 30 g of total fiber from whole grain cereals and cruciferous vegetables. Such measures (low-fat, high-fiber) have the advantage of having no obvious adverse effects and can be implemented now on a public and personal basis while additional options in preventive medicine are being explored.     

Vitamin C intake and apoptosis in normal rectal epithelium.

Apoptosis, or programmed cell death, may lower the risk of neoplasia by removing genetically damaged or mutated cells. A high rate of apoptosis has been linked to a reduced risk of colorectal adenomas; therefore, it is important to understand factors that impact apoptosis. Antioxidants (e.g., vitamin C) protect cells from harmful oxidation processes but may interfere with apoptosis by protecting genetically damaged cells from reactive oxygen species-dependent cell death. The objective of this study was to evaluate the association between vitamin C intake and apoptosis in normal rectal mucosa. Study participants were part of a large, cross-sectional study, the Diet and Health Study III. Participants were recruited from consecutive, consenting patients who underwent colonoscopy at University of North Carolina Hospitals between August 1, 1998 and March 4, 2000. Vitamin C intake, obtained from a food frequency questionnaire, included both dietary sources and vitamin supplements. Apoptosis was measured by morphological evaluation of H&E-stained sections obtained from pinch biopsy samples of normal rectal mucosa in consenting participants (n = 503). The relationship between vitamin C and apoptosis varied by adenoma status. Among individuals with adenomas, there was an inverse linear association between apoptosis and total vitamin C intake. Similarly, individuals with adenomas in the highest quintile of total vitamin C intake were substantially less likely than those in the lowest quintile to have increased colonic apoptosis (odds ratio, 0.05; 95% confidence interval, 0.01-0.46). Vitamin C was not significantly associated with apoptosis in adenoma-free patients. High vitamin C intake was associated with reduced colorectal apoptosis among individuals with adenomas in this study population. Given that high apoptosis may lower colorectal cancer risk, vitamin C supplements may be contraindicated for patients with a history of adenomas.     

Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients

BACKGROUND: Calcium supplements to the western-style diet may reduce the risk for colorectal neoplasia. Using rectal epithelial proliferation (REP) measurements as a biomarker of response to intervention, the authors evaluated the effects of 1-year calcium supplementation in adenoma patients and its possible interactions with the patients' dietary and lifestyle habits. METHODS: Consenting adenoma patients, without a family history of colorectal neoplasia, were randomly selected to receive 3.75 g calcium carbonate (1.5 g Ca2+) daily or to receive no treatment. All had their long-term dietary and lifestyle habits assessed and their REP labeling index (LI) evaluated before and at end of follow-up. The change in LI was compared between groups, and statistical associations were examined between mean nutrient consumption and treatment effect and between lifestyle and treatment effect. RESULTS: Fifty-two adenoma patients (33 treated and 19 untreated) completed intervention and follow-up. There were no significant differences between study groups in age, weight, cigarette smoking, or medication use. The LI decreased in 58% of calcium-intervened patients and in only 26% of nonintervened patients (P = 0.04); the mean LI x 100 (+/- standard deviation) of the former fell from 5.04 +/- 1.93 to 4.54 +/- 1.58, and rose from 4.32 +/- 1.58 to 4.93 +/- 1.58 in the latter (P = 0.04). A lower fat, a higher carbohydrate, fiber, or fluid intake each interacted with the calcium supplementation to decrease the LI (P = 0.02, 0.001, 0.02, and 0.08, respectively). CONCLUSIONS: Long-term calcium supplements significantly suppressed REP in adenoma patients, and long-term dietary habits contributed to this effect. Patient diet should be assessed when researchers use REP as a biomarker in calcium chemoprevention studies. Study results indicated that relevant dietary counseling may be useful in addition to calcium supplements in persons at increased risk for colorectal neoplasia.     

Carotenoids, vitamin A and risk of adenomatous polyp recurrence in the polyp prevention trial

One trial reported beta-carotene supplementation was protective of adenomatous polyp recurrence in nonsmokers. We now examine the relation of serum and dietary carotenoids and vitamin A to adenomatous polyp recurrence in a subcohort of 834 participants in a low fat, high fiber, high fruit and vegetable dietary intervention, the Polyp Prevention Trial. Multivariate odds ratio (OR) and 95% confidence intervals (CI) of polyp recurrence were obtained using baseline or the average (first 3 years of the trial) carotenoid and vitamin A values after adjustment for covariates. Compared to the lowest quartile of baseline alpha-carotene concentrations, the OR of multiple polyp recurrence for the highest quartile was 0.55 (95% CI = 0.30-0.99) and the OR of right-sided recurrence was 0.60 (95% CI = 0.37-0.95). Baseline dietary intakes of alpha-carotene and vitamin A from food with/without supplements were inversely associated with any recurrence (p for linear trend = 0.03-alpha-carotene; p = 0.004 and p = 0.007 -intakes of vitamin A). Compared to the lowest quartile of averaged beta-carotene concentrations, the OR of multiple adenomas for the highest quartile was 0.40 (95% CI = 0.22-0.75) with an inverse trend (p = 0.02). The risk was inversely related to averaged: alpha-carotene concentrations and right-sided polyps; alpha-carotene intake and recurrence of any, multiple and right-sided polyps; beta-carotene intake and multiple adenoma recurrence; vitamin A from food (with supplements) and each adverse endpoint. Thus, alpha-carotene and vitamin A may protect against recurrence in nonsmokers and nondrinkers or be indicative of compliance or another healthy lifestyle factor that reduces risk.     

Supplement use during an intergroup clinical trial for breast cancer (S0221)

The use of supplements during chemotherapy is controversial, partly due to the potential effect of antioxidants on reduced efficacy of chemotherapy-related cytotoxicity. We examined supplement use among breast cancer patients registered to a clinical trial (SWOG 0221) before diagnosis and during treatment. Patients (n = 1,467) completed questionnaires regarding multivitamin and supplement use at trial registration (baseline) to capture use before diagnosis. Of these patients, 1,249 completed a 6-month followup questionnaire to capture use during treatment. We examined the use of vitamins C, D, E, B6, B12, folic acid, and calcium at these timepoints, as well as physician recommendations regarding supplement use. The use of vitamins C, E, folic acid, and calcium decreased during treatment, while the use of vitamin B6 increased. Five hundred seventy four patients (51 %) received no physician recommendations regarding supplement use. Among the remaining 49, 10 % were advised not to take multivitamins and/or supplements, 7 % were advised to use only multivitamins, and 32 % received recommendations to use multivitamins and/or supplements. Among patients who took vitamin C before diagnosis, those who were advised not to take supplements were >5 times more likely not to use of vitamin C during treatment than those not advised to stop use (OR = 5.27, 95 % CI 1.13–24.6). Previous non-users who were advised to take a multivitamin were nearly 5 times more likely to use multivitamins during treatment compared to those who received no recommendation (OR = 4.66, 95 % CI 2.10–10.3). In this clinical trial for high-risk breast cancer, supplement use generally decreased during treatment. Upon followup from the clinical trial, findings regarding supplement use and survival outcomes will better inform physician recommendations for patients on adjuvant chemotherapy.     

Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort

Objective Vitamin E and selenium are promising nutrients for the prevention of prostate cancer, and both are currently being tested in a large randomized trial for prostate cancer. However, results are not expected for at least 6 years. We aimed to investigate the association of vitamin E and selenium supplementation with prostate cancer in the VITamins And Lifestyle (VITAL) study, a cohort study specifically designed to examine supplement use and future cancer risk. Methods In a prospective design, 35,242 men recruited between 2000 and 2002 from western Washington State completed a questionnaire, including detailed questions about vitamin E and selenium supplement intake during the past 10 years from brand-specific multivitamins and single supplements. Using linkage to the western Washington SEER cancer registry, we documented 830 new cases of prostate cancer from baseline through December 2004. Results A 10-year average intake of supplemental vitamin E was not associated with a reduced prostate cancer risk overall [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.65–1.1 for ≥400 IU/day vs. non-use, p for trend 0.36]; however, risk for advanced prostate cancer (regionally invasive or distant metastatic, n = 123) decreased significantly with greater intake of supplemental vitamin E (HR 0.43, 95% CI 0.19–1.0 for 10-year average intake ≥400 IU/day vs. non-use, p for trend 0.03). There was no association between selenium supplementation and prostate cancer risk (HR 0.90, 95% CI 0.62–1.3 for 10-year average intake >50 μg/day vs. non-use, p for trend 0.97). Conclusions In this prospective cohort, long-term supplemental intake of vitamin E and selenium were not associated with prostate cancer risk overall; however, risk of clinically relevant advanced disease was reduced with greater long-term vitamin E supplementation.     

Results and lessons from clinical trials using dietary supplements for cancer: direct and indirect investigations.

Randomized controlled trials are generally regarded as the standard of study designs to determine potential causality. The inclusion of a placebo group in these trials, when appropriate, is generally needed to access the efficacy of a drug or dietary supplement. The recent increasing use of dietary supplements and herbal medications by patients makes it imperative to reevaluate the past findings of clinical studies. Several large-scale trials of dietary supplements have been tested in various populations to determine their effect on cancer prevention. Other trials have focused on patients already diagnosed with cancer. In the latter case, it is difficult to involve a placebo because of the serious nature of the disease. Nevertheless, much has been gleaned from these trials directly and indirectly. Overall, when analyzing primary endpoints in these trials, the results have been discouraging and even support the nonuse of certain supplements because of potential adverse effects. Other secondary endpoints in these same trials have revealed some potential encouraging and discouraging data. Individuals who currently qualify for the potential use of dietary supplements for cancer may be restricted to those who have a deficiency in a certain compound despite adequate dietary sources or lifestyle changes. Those individuals with a smoking history or other unhealthy lifestyle seem to have the most to gain or lose from taking certain dietary supplements for cancer. The time seems more than ripe to evaluate past adequate trials with supplements, such as beta-carotene, N-acetyl-cysteine, selenium, shark cartilage, vitamin C, vitamin E, and others. Again, these studies have been disappointing, but they provide insight for the clinician and patient of what to potentially expect when using these supplements for cancer. In addition, indirect trials for other conditions (cardiovascular) may provide future insight into possible results for future cancer prevention trials.     

A case-control study of diet and the risk of ovarian cancer.

Epidemiologic studies have suggested that some dietary factors may play a role in the etiology of ovarian cancer, but the findings have been inconsistent. We assessed the association of ovarian cancer with dietary factors in a population-based case-control study in Canada. Diet information was collected on 442 incident cases of ovarian cancer diagnosed in 1994 to 1997 and 2,135 population controls via a self-administered questionnaire. Compared with women in the lowest quartile of cholesterol intake, those in the second, third, and fourth quartiles had a multivariate adjusted odds ratio [OR; 95% confidence interval (95% CI)] of 1.12 (0.81-1.56), 1.20 (0.85-1.68), and 1.42 (1.03-1.97), respectively (P for trend = 0.031). Higher egg consumption was also associated with a nonsignificant increase in ovarian cancer risk. The ORs (95% CIs) for ovarian cancer were 0.77 (0.60-1.04) and 0.76 (0.56-0.99) among women in the highest quartile of total vegetable and cruciferous vegetable intake as compared with women in the lowest quartile. Women who took supplements of vitamin E, beta-carotene, and B-complex vitamins for > or =10 years had ORs (95% CIs) of 0.49 (0.30-0.81), 0.31 (0.11-0.91), and 0.61 (0.36-1.05), respectively. However, we did not observe an association of ovarian cancer risk with dietary fat intake, including saturated, monounsaturated, and polyunsaturated fatty acids, protein, carbohydrate, dietary fiber, fruit, dairy products, meat products, fish, chicken, grain products, nut products, baked desserts, margarine, butter, mayonnaise, and supplement of multiple vitamins, vitamin A, vitamin C, calcium, iron, zinc, and selenium. Our findings suggested that ovarian cancer risk was positively associated with higher consumption of dietary cholesterol and eggs and inversely associated with higher intake of total vegetables and cruciferous vegetables and supplementation of vitamin E, beta-carotene, and B-complex vitamins.     

The polyp prevention trial continued follow-up study: no effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization.

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), and low-fat (20% of total energy) diet on the recurrence of adenomatous polyps in the large bowel over a period of 4 years. Although intervention participants reported a significantly reduced intake of dietary fat, and increased fiber, fruit, and vegetable intakes, their risk of recurrent adenomas was not significantly different from that of the controls. Since the PPT intervention lasted only 4 years, it is possible that participants need to be followed for a longer period of time before treatment differences in adenoma recurrence emerge, particularly if diet affects early events in the neoplastic process. The PPT-Continued Follow-up Study (PPT-CFS) was a post-intervention observation of PPT participants for an additional 4 years from the completion of the trial. Of the 1,905 PPT participants, 1,192 consented to participate in the PPT-CFS and confirmed colonoscopy reports were obtained on 801 participants. The mean time between the main trial end point colonoscopy and the first colonoscopy in the PPT-CFS was 3.94 years (intervention group) and 3.87 years (control group). The baseline characteristics of 405 intervention participants and 396 control participants in the PPT-CFS were quite similar. Even though the intervention group participants increased their fat intake and decreased their intakes of fiber, fruits, and vegetables during the PPT-CFS, they did not go back to their prerandomization baseline diet (P < 0.001 from paired t tests) and intake for each of the three dietary goals was still significantly different from that in the controls during the PPT-CFS (P < 0.001 from t tests). As the CFS participants are a subset of the people in the PPT study, the nonparticipants might not be missing completely at random. Therefore, a multiple imputation method was used to adjust for potential selection bias. The relative risk (95% confidence intervals) of recurrent adenoma in the intervention group compared with the control group was 0.98 (0.88-1.09). There were no significant intervention-control group differences in the relative risk for recurrence of an advanced adenoma (1.06; 0.81-1.39) or multiple adenomas (0.92; 0.77-1.10). We also used a multiple imputation method to examine the cumulative recurrence of adenomas through the end of the PPT-CFS: the intervention-control relative risk (95% confidence intervals) for any adenoma recurrence was 1.04 (0.98-1.09). This study failed to show any effect of a low-fat, high-fiber, high-fruit and -vegetable eating pattern on adenoma recurrence even with 8 years of follow-up. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1745-52).     

Effects of dietary wheat bran fiber on rectal epithelial cell proliferation in patients with resection for colorectal cancers

A preponderance of carcinogenesis studies in rodents and epidemiologic studies in humans suggests a potential role of dietary fiber in the prevention of colorectal cancer. Recently, wheat bran fiber used as a dietary supplement has been shown to decrease the growth of rectal adenomatous polyps in patients with familial polyposis; however, few studies of high-risk human populations have been attempted to determine the effects of dietary fiber supplementation on markers of carcinogenesis in the colon or rectum. We have designed a one-arm study to evaluate the effects of dietary supplementation with wheat bran fiber [i.e., 13.5 g/day for 8 wk; after 1 mo, 2 g/day (compliance evaluation period)] on [3H]thymidine rectal mucosa cell labeling (i.e., percent of epithelial cells incorporating [3H]thymidine into DNA in intact rectal crypt cells over a 90-min exposure as well as in minced rectal biopsy tissue over a 24-hr exposure) in rectal biopsy specimens. The biopsy specimens were obtained at sigmoidoscopy in 17 compliant patients with a history of resected colon or rectal cancer. We categorized patients as having initially low or initially high [3H]thymidine-labeling indices (i.e., percent of mucosa cells that incorporate [3H]thymidine into DNA during 1.5- or 24-hour in vitro incubations) by using the median baseline labeling index as a cutoff between high and low values. On the basis of a chi-square test used to identify patients with a statistically significant (P less than .001) change, six of the eight patients who initially had high 24-hour outgrowth labeling indices showed a significant decrease in the rectal mucosa biopsy specimens obtained after treatment. An overall 22% decrease was observed in rectal mucosa cell biopsy specimens obtained at study termination (P less than .001). Of the eight patients with initially high total [3H]thymidine-labeling indices in crypt organ culture, four had a significant (P less than .001) decrease from baseline values, one had a significant increase, and three showed no change following the fiber intervention. The wheat bran fiber dietary supplement of 13.5 g/day was well tolerated by this group of older (54-70 yr) patients. Although the [3H]-thymidine labeling index data suggest that the wheat bran fiber supplement can inhibit DNA synthesis and rectal mucosa cell proliferation in high-risk patients, the results of this small pilot study should not be overinterpreted vis à vis the potential role of wheat bran fiber as a chemopreventive agent for colorectal cancer.(ABSTRACT TRUNCATED AT 400 WORDS)     

A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps

Because supplements of vitamins C and E had been associated with reduction of fecal mutagen levels, a double-blind randomized trial was designed to examine the effects of these vitamins on the rate of recurrence of colorectal polyps, presumed precursors for colorectal cancer. Two hundred patients believed to be free of polyps after removal of at least one colorectal polyp were randomized to receive a supplement of 400 mg each of ascorbic acid and alpha-tocopherol, or a placebo. Fifteen patients had to be excluded because a review of pathology indicated that their polyps were not adenomatous. A second colonoscopic examination was planned after 2 yr of supplementation. One hundred thirty-seven people (75% of eligible subjects) completed the study; polyps were observed in the second colonoscopy in 41.4% of 70 subjects on vitamin supplements and in 50.7% of 67 subjects on placebos. After adjustment for differences between groups in demographic and dietary factors before study entry, the relative risk of polyp occurrence was 0.86, with 95% confidence limits from 0.51 to 1.45, in an analysis of 129 subjects with complete information on demographic and dietary factors who had completed the trial. Of the 48 patients who had not completed the study, 7 had died, 33 had not returned to their physician for an examination, and 8 had had a follow-up colonoscopy or sigmoidoscopy. Inclusion of the three polyps found in these eight examinations led to an estimate of relative risk of 0.86 (95% confidence limits, 0.51 to 1.43). The findings of this investigation suggest that any reduction in the rate of polyp recurrence associated with vitamin supplementation is small, and a larger study would be required to ensure that an effect of this size was not a chance finding.     

Feasibility of a randomized controlled trial of vitamin D vs. placebo in women with recently diagnosed breast cancer

Low serum vitamin D levels have been associated with poor outcomes in women diagnosed with early breast cancer. However, no randomized controlled trials (RCTs) have been performed to determine whether vitamin D supplementation might be an effective intervention in this population. We prospectively evaluated vitamin D adequacy and supplementation rates in a contemporary cross-sectional sample of breast cancer patients from 2 large urban centers and examined the feasibility of an RCT of vitamin D supplementation. Women with recently diagnosed early breast cancer were prospectively identified and recruited in Toronto and Los Angeles between March 2009 and January 2010. Anthropometric measurements, dietary, lifestyle, and medication histories were obtained by means of structured questionnaires and interviews. Tumor and treatment characteristics were abstracted from clinical records and blood samples were collected for analysis of 25-OH vitamin D. 173 eligible patients (median age 57) were enrolled. Clinical and treatment characteristics were similar between centres. 84.4 % of women reported use of vitamin D-containing supplements with median daily doses of 1,400 IU. Median 25-OH vitamin D levels were 85.5 and 98.5 nmol/L (P = 0.1), and levels of deficiency (<50 nmol/L), insufficiency (50-72 nmol/L), and adequacy (>72 nmol/L) were 3.8, 23.8, 72.5 % (Toronto) and 4.3, 20.7, 75 % (Los Angeles). 25-OH vitamin D levels were strongly correlated with vitamin D supplement use (r = 0.41, P < 0.0001). 68 % of women expressed willingness to participate in a vitamin D supplementation RCT; however, only 12.7 % of the study population met the pre-specified feasibility criteria (25-OH vitamin D <72 nmol/L, willing to participate, and taking ≤1,000 IU vitamin D supplement/day). Both vitamin D levels and supplementation rates are higher than in previous reports. While the majority of women would be willing to participate in an RCT of vitamin D supplementation, low levels of deficiency/insufficiency and high rates of supplement use would limit the feasibility of such a study.     

Dietary supplement use among cancer survivors and the general population: a nation-wide cross-sectional study

Background

Use of dietary supplements among cancer survivors is common and controversial, but information on the amount of nutrients from supplements among cancer survivors is limited. We examined the amount of nutrients and their contribution to total nutrient intake from supplements and compared these data between cancer survivors and cancer-free individuals. We also identified factors associated with supplement use among cancer survivors.

Methods

We identified 400 cancer survivors and 10,387 cancer-free individuals, aged ≥?19 years, from the fifth Korea National Health and Nutrition Examination Survey (KNHANES) V-1, 2 (2010, 2011). We calculated the amount of nutrients consumed from foods and supplements, the percent contributions of supplement nutrients to total nutrient intakes and cancer survivors’ nutrient intakes relative to the Estimated Average Requirements (EARs) and the Tolerable Upper Intake Levels (ULs). We examined factors associated with supplement use among cancer survivors.

Results

We found that 33.3% of cancer survivors and 22.1% of cancer-free individuals reported the use of dietary supplements. Compared to cancer-free individuals, cancer survivors had higher intakes of riboflavin, folate, and iron from foods (p?<?0.05 for each), and higher intakes of calcium (p?=?0.05) and vitamin C (p?=?0.01) from foods and supplements. The similar pattern was observed for the percent contributions to total nutrient intake. Cancer survivors had higher proportion of participants below EARs than cancer-free individuals for thiamin and niacin (p?<?0.05 for each). The proportions of cancer survivors below the EARs were 61.2% for calcium, 49.1% for riboflavin, and 43.5% for folate and the proportions of cancer survivors above the ULs were 3.3% for iron, and 2.3% for vitamin A. For female cancer survivors, education above an elementary school level, moderate physical activity, low vegetable intake, and high circulating vitamin D levels were associated with supplement use. For male cancer survivors, living in an urban area, no consumption of alcohol, and lower energy intake, were associated with supplement use.

Conclusions

Korean cancer survivors have higher rate of dietary supplement use and higher contribution from supplements to total nutrient intake than cancer-free individuals. Demographic and lifestyle factors were associated with supplement use among cancer survivors.