Changes in serum retinol,alpha-tocopherol,vitamin C,carotenoids, xinc and selenium after micronutrient supplementation during alcohol rehabilitation

OBJECTIVE: To test the effect of a 21-day supplementation with moderate doses of antioxidant nutrients on biochemical indicators of vitamin, carotenoid and trace element levels in alcohol-dependent patients during a program of alcohol rehabilitation. DESIGN: A randomized double-blind trial was performed comparing two groups receiving daily either a combination of micronutrients (beta-carotene: 6 mg, vitamin C: 120 mg, vitamin E: 30 mg, zinc: 20 mg, selenium: 100 micro g) or a placebo. SUBJECTS: 106 alcohol-dependent patients 20 to 60 years of age without severe liver disease, hospitalized for a 21-day rehabilitation program. Measure of Outcome: Vitamin C, retinol, alpha-tocopherol, zeaxanthin/lutein, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, zinc and selenium were measured in serum, initially and after supplementation. RESULTS: (1) In the placebo group, after 21 days of rehabilitation, serum concentrations of vitamin C and all five carotenoids significantly increased, whereas retinol and alpha-tocopherol concentrations decreased; zinc and selenium levels were unaffected. (2) At the end of the hospital stay, serum indicators were significantly improved in the supplement group as compared to the placebo group for vitamin C, alpha-tocopherol, beta-carotene, zinc and selenium; conversely, lycopene changes were higher in the placebo group than in supplement group. (3) Of the serum antioxidants measured at entrance, only vitamin C was significantly depleted in heavy smokers, and, after the supplementation period, vitamin C was efficiently repleted in this later group. CONCLUSION: Our results indicate that a short-term supplementation with physiological doses of antioxidant vitamins, carotenoids and trace elements during alcohol rehabilitation clearly improves micronutrient status indicators. Heavy smokers in particular seem to respond to vitamin C supplementation.     

Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population

OBJECTIVE: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc. METHODS: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. RESULTS: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. CONCLUSION: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.     

Micronutrient Intake and Risk of Hematological Malignancies in Adults: A Systematic Review and Meta-analysis of Cohort Studies

There has been accumulating evidence that several micronutrients may play a protective role in the risk of solid cancers. However, their role in hematological malignancies remains to be elucidated; this meta-analysis aims to evaluate the associations between micronutrient intake as well as supplementation and risk of hematological cancer in adults. Eligible cohort studies (examining intake of vitamin A, vitamin C, vitamin D, vitamin E, lycopene, folate, iron, carotenoids, beta-carotene, selenium, pyridoxine) were sought in PubMed up to July 31, 2016. Random-effects models were used for the calculation of pooled relative risks (RR) with their 95% confidence intervals (CI). Twelve cohort studies were deemed eligible. Null associations were noted regarding supplemented vitamin A (pooled relative risk [RR]?=?0.92, 95% confidence interval [CI]: 0.80–1.07), supplemented vitamin C (pooled RR?=?1.00, 95%CI: 0.90–1.12), total vitamin D (pooled RR?=?1.05, 95%CI: 0.91–1.20), supplemented vitamin E (pooled RR?=?0.98, 95%CI: 0.88–1.10), and dietary lycopene intake (pooled RR?=?1.00, 95%CI: 0.86–1.16) and the risk of non-Hodgkin lymphoma. No summary estimates are provided for other hematological malignancies due to the limited number of studies. Future prospective trials should be conducted for a better understanding of this field; especially regarding Hodgkin lymphoma, leukemia and plasma cell neoplasms, on which data are scarce.     

Nutritional factors and susceptibility to arsenic-caused skin lesions in West Bengal, India

There has been widespread speculation about whether nutritional deficiencies increase the susceptibility to arsenic health effects. This is the first study to investigate whether dietary micronutrient and macronutrient intake modulates the well-established human risk of arsenic-induced skin lesions, including alterations in skin pigmentation and keratoses. The study was conducted in West Bengal, India, which along with Bangladesh constitutes the largest population in the world exposed to arsenic from drinking water. In this case-control study design, cases were patients with arsenic-induced skin lesions and had < 500 microg/L arsenic in their drinking water. For each case, an age- and sex-matched control was selected from participants of a 1995-1996 cross-sectional survey, whose drinking water at that time also contained < 500 microg/L arsenic. Nutritional assessment was based on a 24-hr recall for major dietary constituents and a 1-week recall for less common constituents. Modest increases in risk were related to being in the lowest quintiles of intake of animal protein [odds ratio (OR) = 1.94; 95% confidence interval (CI), 1.05-3.59], calcium (OR = 1.89; 95% CI, 1.04-3.43), fiber (OR = 2.20; 95% CI, 1.15-4.21), and folate (OR = 1.67; 95% CI, 0.87-3.2). Conditional logistic regression suggested that the strongest associations were with low calcium, low animal protein, low folate, and low fiber intake. Nutrient intake was not related to arsenic exposure. We conclude that low intake of calcium, animal protein, folate, and fiber may increase susceptibility to arsenic-caused skin lesions. However, in light of the small magnitude of increased risks related to these dietary deficiencies, prevention should focus on reducing exposure to arsenic.     

Micronutrient Malnutrition, Infection, and Immunity: An Overview

Micronutrient deficiencies and infectious diseases often coexist and exhibit complex interactions leading to the vicious cycle of malnutrition and infections among underprivileged populations of the developing countries, particularly in preschool children. Several micronutrients such as vitamin A, beta-carotene, folic acid, vitamin B_12, vitamin C, riboflavin, iron, zinc, and selenium, have immunomodulating functions and thus influence the susceptibility of a host to infectious diseases and the course and outcome of such diseases. Certain of these micronutrients also possess antioxidant functions that not only regulate immune homeostasis of the host, but also alter the genome of the microbes, particularly in viruses, resulting in grave consequences like resurgence of old infectious diseases or the emergence of new infections. These micronutrient infection and immune function interactions and their clinical and public health relevance in developing countries are briefly reviewed in this article.     

Supplementation with mixed fruit and vegetable juice concentrates increased serum antioxidants and folate in healthy adults

OBJECTIVE: Epidemiological studies have shown that low plasma levels of antioxidant micronutrients, which are commonly found in fruit and vegetables, are associated with increased risk for diseases such as heart disease, cancer, metabolic disorders and the like. The aim of this study was to monitor the dietary habits of a group of healthy, middle-aged, men and women and to assess the effect of supplementation with a natural phytonutrient preparation from fruits and vegetables, on plasma levels of various antioxidant micronutrients and oxidative stress assessed by measuring 8-oxodGuo (8-oxo-7,8-dihydro-2'-deoxyguanosine) in urine. METHODS: The study followed a double-blind randomized cross-over design involving 59 healthy men and women (40-60 years of age). The supplement or a placebo was given to two groups for a total period of 14 weeks (crossover week 7). Blood levels of beta-carotene, vitamin C, vitamin E, selenium and folate were measured at 0, 7 and 14 weeks. Fruit and vegetable consumption was monitored by means of a retrospective food frequency questionnaire at week 0, 7 and 14. Urinary 8-oxodGuo was also determined at these time points. RESULTS: Significant increases in blood nutrient levels after active supplementation were observed for beta-carotene, vitamin C, vitamin E, selenium and folate. Ranges measured, after supplementation, often fell into those associated with a reduced risk for disease. Our data suggests that, although generally health conscious, participants still fell short of the recommended five portions of fruit and vegetables per day. No significant group changes were noted for 8-oxodGuo concentration in urine. CONCLUSION: Supplementation with mixed fruit and vegetable juice concentrates effectively increased plasma levels of important antioxidant nutrients and folate.     

Dietary vitamins A, C, and E and selenium as risk factors for cervical cancer

The relation between cervical cancer and dietary intake of vitamins A, C, and E, beta-carotene, and selenium was examined in a population-based case-control study in Utah. Cervical cancer cases (n = 266) and population-based controls (n = 408) were interviewed between 1984 and 1987. Protective effects were observed for vitamins A, C, and E and beta-carotene but were attenuated by age, level of education, and lifetime cigarette use. Associated risk (comparing highest with lowest quartiles of intake) went from 0.53 (crude) to 0.71 (adjusted) for vitamin A; from 0.55 (crude) to 0.82 (adjusted) for beta-carotene; from 0.45 (crude) to 0.55 (adjusted) for vitamin C; from 0.58 (crude) to 0.60 (adjusted) for vitamin E; and from 0.95 (crude) to 0.70 (adjusted) for selenium. Adjustment for number of sex partners and church attendance, factors significantly related to cervical cancer risk, only slightly attenuated these adjusted risk estimates.     

Arsenic in drinking water and skin lesions: dose-response data from West Bengal,India

BACKGROUND: Over 6 million people live in areas of West Bengal, India, where groundwater sources are contaminated with naturally occurring arsenic. The key objective of this nested case-control study was to characterize the dose-response relation between low arsenic concentrations in drinking water and arsenic-induced skin keratoses and hyperpigmentation. METHODS: We selected cases (persons with arsenic-induced skin lesions) and age- and sex-matched controls from participants in a 1995-1996 cross-sectional survey in West Bengal. We used a detailed assessment of arsenic exposure that covered at least 20 years. Participants were reexamined between 1998 and 2000. Consensus agreement by four physicians reviewing the skin lesion photographs confirmed the diagnosis in 87% of cases clinically diagnosed in the field. RESULTS: The average peak arsenic concentration in drinking water was 325 microg/liter for cases and 180 microg/liter for controls. The average latency for skin lesions was 23 years from first exposure. We found strong dose-response gradients with both peak and average arsenic water concentrations. CONCLUSIONS: The lowest peak arsenic ingested by a confirmed case was 115 microg/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions.     

Dietary antioxidants and lung cancer risk: a case-control study in Uruguay.

To examine the protective role of dietary antioxidants (carotenoids, vitamin C, vitamin E, glutathione, and flavonoids) in lung cancer risk, a case-control study involving 541 cases of lung cancer and 540 hospitalized controls was carried out in Uruguay. The relevant variables were energy adjusted using the residuals method and then categorized in quartiles. Adjusted odds ratios (ORs) for antioxidants were calculated through unconditional logistic regression. With the exception of lycopene and vitamin C, the remaining antioxidants were associated with significant reductions in risk of lung cancer. Of particular interest was the inverse association between dietary glutathione and lung cancer [OR of quartile with highest intake compared with lowest quartile = 0.42, 95% confidence interval (CI) = 0.27-0.63]. Also, carotenoids and vitamin E were associated with significant reductions in risk of lung cancer (OR = 0.43, 95% CI = 0.29-0.64 for total carotenoids and OR = 0.50, 95% CI = 0.39-0.85 for vitamin E). A joint effect for high vs. low intakes of beta-carotene and glutathione was associated with a significant reduction in risk (OR = 0.32, 95% CI = 0.22-0.46). It could be concluded that dietary antioxidants are associated with a significant protective effect in lung carcinogenesis and that the inverse association for glutathione persisted after controlling for total vegetables and fruits.     

Effects of a low-fat vegan diet and a Step II diet on macro- and micronutrient intakes in overweight postmenopausal women

OBJECTIVE: This study investigated the nutrient intake of overweight postmenopausal women assigned to a low-fat vegan diet or a Step II diet. METHODS: Fifty-nine overweight (body mass index, 26 to 44 kg/m2) postmenopausal women were randomly assigned to a self-selected low-fat vegan or a National Cholesterol Education Program Step II diet in a 14-wk controlled trial on weight loss and metabolism. Nutrient intake, which was measured per 1000 kcal, was the main outcome measure. Statistical analyses included within-group and between-group t tests examining changes associated with each diet. RESULTS: Consumption of a low-fat vegan diet was associated with greater decreases in fat, saturated fat, protein, and cholesterol intakes and greater increases in carbohydrate, fiber, beta-carotene, and total vitamin A intakes than was a Step II diet. The low-fat vegan group also increased thiamin, vitamin B6, and magnesium intakes more than the Step II group, and both groups increased folic acid, vitamin C, and potassium intakes. If considering only food sources of micronutrients, the low-fat vegan group decreased vitamin D, vitamin B12, calcium, selenium, phosphorous, and zinc intakes compared with baseline. However, with incidental supplements included, decreases were evident only in phosphorous and selenium intakes. No micronutrient decreases were found in the Step II group. CONCLUSIONS: Individuals on a low-fat vegan or Step II diet should take steps to meet the recommended intakes of vitamin D, vitamin K, folic acid, calcium, magnesium, and zinc. Individuals on a low-fat vegan diet should also ensure adequate intakes of vitamin B12, phosphorous, and selenium.     

Associations between drinking water and urinary arsenic levels and skin lesions in Bangladesh

The present study examined the associations between drinking water and urinary arsenic levels and skin lesions among 167 residents of three contiguous villages in Bangladesh. Thirty-six (21.6%) had skin lesions (melanosis, hyperkeratosis, or both), of which 13 (36.1%) occurred in subjects who were currently drinking water containing concentrations of arsenic < 50 micrograms/L. The risk for skin lesions in relation to the exposure estimates based on urinary arsenic was elevated more than 3-fold, with the odds ratios for the highest versus the lowest quartiles being 3.6 (95% confidence interval, 1.2 to 12.1) for urinary total arsenic and 3.2 (95% confidence interval, 1.1 to 10.0) for urinary creatinine-adjusted total arsenic. The risks for skin lesions in relation to the exposure estimates based on arsenic in drinking water were less strongly elevated, with the odds ratios for the highest versus the lowest quartiles of exposure being 1.7 (95% confidence interval, 0.6 to 5.1) for drinking-water arsenic and 2.3 for cumulative arsenic index. The study suggests that arsenic exposure is associated with skin lesions in the Bangladesh population and that urinary arsenic may be a stronger predictor of skin lesions than arsenic in drinking water in this population.     

The comparative impact of iron, the B-complex vitamins, vitamins C and E, and selenium on diarrheal pathogen outcomes relative to the impact produced by vitamin A and zinc

Micronutrient supplementation offers one of the most cost-effective means of improving the health and survival of children in developing countries. However, the effects of supplementation with single micronutrients on diarrhea are not always consistent, and supplementation with multi-micronutrient supplements can have negative effects. These inconsistencies may result from the failure to consider the diverse etiological agents that cause diarrhea and the unique effects each micronutrient has on the immune response to each of these agents. This review examines the separate effects that supplementation with the B-complex vitamins, vitamin C, vitamin E, selenium, and iron have on diarrheal disease-related outcomes. Supplementation with iron may increase the risk of infection by invasive diarrheal pathogens, while supplementation with the remaining micronutrients may reduce this risk. These differences may be due to distinct regulatory effects each micronutrient has on the pathogen-specific immune response, as well as on the virulence of specific pathogens. The findings of these studies suggest that micronutrient supplementation of children must take into account the pathogens prevalent within communities as reflected by their diarrheal disease burdens. The effectiveness of combining multiple micronutrients into one supplement must also be reconsidered.     

Relations between vegetable, fruit and micronutrient intake. Implications for odds ratios in a case-control study

OBJECTIVE: To investigate whether the protection observed for some micronutrients, such as beta-carotene, in several observational studies may simply reflect vegetable and fruit intake. DESIGN: A case-control study conducted in Italy. SUBJECTS: The subjects were 1225 colon cancer patients, 728 rectal cancer patients and 4154 hospital controls. RESULTS: For the 16 micronutrients considered, the more closely a micronutrient was correlated with total vegetable and fruit intake, the more it appeared protective against colorectal cancer. CONCLUSION: When studying the effect of a nutrient on disease risk in an observational setting, its relation to other nutrients and foods must be taken into account.     

Micronutrients: dietary intake v. supplement use

Whilst clinical deficiency of micronutrients is uncommon in the developed world, a suboptimal intake of certain micronutrients has been linked with an increased risk of chronic diseases such as CVD and cancer. Attention has therefore focused on increasing micronutrient status in order to theoretically reduce chronic disease risk. Increasing micronutrient status can involve a number of approaches: increasing dietary intake of micronutrient-rich foods; food fortification; use of supplements. Observational cohort studies have demonstrated an association between high intakes of micronutrients such as vitamin E, vitamin C, folic acid and beta-carotene, and lower risk of CHD, stroke and cancer at various sites. However, randomised intervention trials of micronutrient supplements have, to date, largely failed to show an improvement in clinical end points. The discordance between data from cohort studies and the results so far available from clinical trials remains to be explained. One reason may be that the complex mixture of micronutrients found, for example, in a diet high in fruit and vegetables may be more effective than large doses of a small number of micronutrients, and therefore that intervention studies that use single micronutrient supplements are unlikely to produce a lowering of disease risk. Studies concentrating on whole foods (e.g. fruit and vegetables) or diet pattern (e.g. Mediterranean diet pattern) may be more effective in demonstrating an effect on clinical end points. The present review will consider the clinical trial evidence for a beneficial effect of micronutrient supplements on health, and review the alternative approaches to the study of dietary intake of micronutrients.     

The role of micronutrients in heart failure

Heart failure is a common condition in the Western world, particularly among elderly persons and with an ever-aging population, the incidence is expected to increase. Diet in the setting of heart failure is important--patients with this condition are advised to consume a low-salt diet and monitor their weight closely. Nutritional status of patients with heart failure also is important--those with poor nutritional status tend to have a poor long-term prognosis. A growing body of evidence suggests an association between heart failure and micronutrient status. Reversible heart failure has been described as a consequence of severe thiamine and selenium deficiency. However, contemporary studies suggest that a more subtle relationship may exist between micronutrients and heart failure. This article reviews the existing literature linking heart failure and micronutrients, examining studies that investigated micronutrient intake, micronutrient status, and the effect of micronutrient supplementation in patients with heart failure, and focusing particularly on vitamin A, vitamin C, vitamin E, thiamine, other B vitamins, vitamin D, selenium, zinc, and copper.     

A randomized, double-blind placebo-controlled trial evaluating the effects of vitamin E and selenium on arsenic-induced skin lesions in Bangladesh

OBJECTIVE: We sought to determine whether supplementation of vitamin E (alpha-tocopherol), selenium (L-selenomethionine), or their combination improves arsenical skin lesions. METHODS: A 2 x 2 randomized, placebo-controlled, double-blind trial among 121 men and women chronically exposed to arsenic in drinking water was conducted in rural Bangladesh. Participants were randomized to one of four treatment arms: vitamin E, selenium, vitamin E and selenium (combination), or placebo and were treated for 6 months. RESULTS: At baseline, the average skin lesion scores were 2.23, 2.26, and 2.63 and at follow-up, the average skin lesion scores went down to 2.00, 2.06, and 2.47 in those receiving vitamin E, selenium, and the combination, respectively. CONCLUSIONS: Supplementation with vitamin E and selenium, either alone or in combination, slightly improved skin lesion status, although the improvement was not statistically significant.     

Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India

A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.     

Redistribution of vitamin A after iron supplementation in Indonesian infants

BACKGROUND: Deficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. OBJECTIVE: This study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements. DESIGN: In a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. RESULTS: Iron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the non-supplemented infants. In contrast, the modified relative dose response of the iron-supplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but beta-carotene supplementation did not significantly improve vitamin A status. CONCLUSIONS: In this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status.     

High dietary iron and copper and risk of colorectal cancer: a case-control study in Burgundy, France

Several hypotheses have been proposed for colorectal carcinogenesis, including formation of free radicals. A case-control study compared nutrient intake in 171 colorectal cancer cases versus 309 general population controls, using a detailed face-to-face food history questionnaire. A food composition table enabled us to determine the mean composition of the diet in macro- and micronutrients. Dietary intakes were separately categorized into quartiles by gender. Logistic regression models were adjusted for age, sex, energy, exercise, and body mass index. High energy, copper, iron, and vitamin E intakes were associated with an overall increased risk of colorectal cancer. The odds ratios associated with the fourth quartile of intake were 2.3 (95% confidence interval, 1.3-4.0), 2.4 (1.3-4.6), 2.2 (1.1-4.7), and 1.8 (1.0-3.4) for energy, copper, iron, and vitamin E, respectively. There were no significant associations with dietary fiber, folate, calcium, or antioxidant vitamins other than vitamin E. These findings regarding iron and copper suggest that free radicals play an important role in colorectal carcinogenesis, while the findings regarding vitamin E are so far unexplained.