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LE Magazine March 2001

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Prostate cancer

Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer.

BACKGROUND: Selenium and alpha-tocopherol, the major form of vitamin E in supplements, appear to have a protective effect against prostate cancer. However, little attention has been paid to the possible role of gamma-tocopherol, a major component of vitamin E in the U.S. diet and the second most common tocopherol in human serum. A nested case-control study was conducted to examine the associations of alpha-tocopherol, gamma-tocopherol, and selenium with incident prostate cancer. METHODS: In 1989, a total of 10 456 male residents of Washington County, MD, donated blood for a specimen bank. A total of 117 of 145 men who developed prostate cancer and 233 matched control subjects had toenail and plasma samples available for assays of selenium, alpha-tocopherol, and gamma-tocopherol. The association between the micronutrient concentrations and the development of prostate cancer was assessed by conditional logistic regression analysis. All statistical tests were two-sided. RESULTS: The risk of prostate cancer declined, but not linearly, with increasing concentrations of alpha-tocopherol (odds ratio (highest versus lowest fifth) = 0.65; 95% confidence interval = 0.32-1.32; P:(trend) =.28). For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth (P:(trend) =.002). The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth (P:(trend) =.27). Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high. CONCLUSIONS: The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium.

J Natl Cancer Inst 2000 Dec 20;92(24):2018-2023

Under-used form of vitamin E may be the most protective against prostate cancer.

Scientists at the Johns Hopkins School of Public Health have found that higher blood levels of gamma-tocopherol, a form of vitamin E not usually included in vitamin supplements, is associated with a lower risk of developing prostate cancer than is alpha-tocopherol, the synthetic form of vitamin E most commonly found in supplements. Although seldom studied, gamma-tocopherol is a natural form of vitamin E routinely found in the U.S. diet, notably in soy foods. The study also revealed that high concentrations of gamma-tocopherol appear to boost the prostate cancer-fighting abilities of both alpha-tocopherol and the micronutrient selenium. The study appears in the December 20, 2000 issue of the Journal of the National Cancer Institute, where it is accompanied by an editorial.

“Given gamma-tocopherol's positive interactions with both alpha-tocopherol and selenium,” says Kathy J. Helzlsouer, MD, MHS, professor, Epidemiology, the Johns Hopkins School of Public Health, and the lead investigator of the study, “its use should be considered in upcoming prostate cancer prevention trials.” A previous intervention trial, designed to look at the effects of supplemental alpha-tocopherol on the risk of lung cancer among smokers, had observed that the men taking the supplements had a lower risk of developing prostate cancer. Little attention, however, has been paid to other forms of vitamin E such as gamma-tocopherol, which studies in cells suggest may have even stronger antioxidant properties than alpha-tocopherol. The present study is the first to simultaneously investigate the association between the risk of prostate cancer and concentrations of alpha-tocopherol, gamma-tocopherol, and selenium. It is also the first to simultaneously consider the association between the risk of prostate cancer and concentrations of these micronutrients when they are supplied primarily from normal dietary intake (i.e., not from supplements). In a countywide campaign in 1989, researchers from the Johns Hopkins School of Public Health collected and froze blood samples from a total of 10,456 male residents of Washington County, Md., for future study. At the time of blood donation, participants gave information about their medical and smoking histories; all supplements and medications taken within the past 48 hours; and their height and weight, both currently and at age 21. Each participant was also asked to mail in a nail clipping from the big toe so that selenium levels could be assessed. Among the men who gave a blood sample and nail clipping in 1989, 110 went on to develop prostate cancer between January 1990 and September 1996. Each of these men with prostate cancer were matched with two controls, men who had remained cancer-free. Serum levels of alpha-tocopherol and gamma-tocopherol, as well as toenail selenium levels, were measured and compared between the two groups. The researchers then compared all three micronutrients' concentrations, both singly and in combination, with each man's risk of developing prostate cancer. Median concentrations of both alpha-tocopherol and gamma-tocopherol were lower among the men with prostate cancer than among the control subjects, but these differences were statistically significant only for gamma-tocopherol. Compared with the men with the lowest levels of gamma-tocopherol, men with the highest levels had a fivefold reduction in their risk of developing prostate cancer. What is more, gamma-tocopherol appeared to boost the protective effects of both alpha-tocopherol and selenium. That is, compared with individuals with low concentrations of all three micronutrients, high concentrations of selenium and alpha-tocopherol were associated with a statistically significant decreased risk of prostate cancer only when high concentrations of gamma-tocopherol were also present.

The authors note that since alpha-tocopherol supplementation may lower gamma-tocopherol concentrations in plasma and tissues, supplementation with combined alpha- and gamma-tocopherol may be called for in future prostate cancer prevention trials. Support for this study was provided by a Public Health Service grant from the National Cancer Institute at the National Institutes of Health, and by grants from the Department of Defense.


Vegetable/Mineral consumption

Dietary intake of whole grains.

OBJECTIVE: The objective of this study was to provide national estimates of whole-grain intake in the United States, identify major dietary sources of whole grains and compare food and nutrient intakes of whole-grain consumers and nonconsumers. METHODS: Data were collected from 9,323 individuals age 20 years and older in USDA's 1994-96 Continuing Survey of Food Intakes by Individuals through in-person interviews on two non-consecutive days using a multiple-pass 24-hour recall method. Foods reported by respondents were quantified in servings as defined by the Food Guide Pyramid using a new database developed by the USDA. Whole-grain and nonwhole-grain servings were determined based on the proportion, by weight, of the grain ingredients in each food that were whole grain and nonwhole grain. Sampling weights were applied to provide national probability estimates adjusted for differential rates of selection and nonresponse. Then, tests were used to assess statistically significant differences in intakes of nutrients and food groups by whole-grain consumers and nonconsumers. RESULTS: According to the 1994-96 survey, U.S. adults consumed an average of 6.7 servings of grain products per day; 1.0 serving was whole grain. Thirty-six percent averaged less than one whole-grain serving per day based on two days of intake data, and only eight percent met the recommendation to eat at least three servings per day. Yeast breads and breakfast cereals each provided almost one-third of the whole-grain servings, grain-based snacks provided about one-fifth, and less than one-tenth came from quick breads, pasta, rice, cakes, cookies, pies, pastries and miscellaneous grains. Whole-grain consumers had significantly better nutrient profiles than nonconsumers, including higher intakes of vitamins and minerals as percentages of 1989 Recommended Dietary Allowances and as nutrients per 1,000 kilocalories, and lower intakes of total fat, saturated fat and added sugars as percentages of food energy. Consumers were significantly more likely than nonconsumers to meet Pyramid recommendations for the grain, fruit and dairy food groups. CONCLUSION: Consumption of whole-grain foods by U.S. adults falls well below the recommended level. A large proportion of the population could benefit from eating more whole grain, and efforts are needed to encourage consumption.

J Am Coll Nutr 2000 Jun;19(3 Suppl):331S-38S

Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects.

BACKGROUND: Recommendations by the UK Department of Health suggest that protection from neural tube defects (NTD) can be achieved through intakes of an extra 400 microgram daily of folate/folic acid as natural food, foods fortified with folic acid, or supplements. The assumption is that all three routes of intervention would have equal effects on folate status. METHODS: We assessed the effectiveness of these suggested routes of intervention in optimising folate status. 62 women were recruited from the University staff and students to take part in a 3-month intervention study. Participants were randomly assigned to one of the following five groups: folic acid supplement (400 microgram/day; I); folic-acid-fortified foods (an additional 400 microgram/day; II); dietary folate (an additional 400 microgram/day; III); dietary advice (IV), and control (V). Responses to intervention were assessed as changes in red-cell folate between pre-intervention and post-intervention values. FINDINGS: 41 women completed the intervention study. Red-cell folate concentrations increased significantly over the 3 months in the groups taking folic acid supplements (group I) or food fortified with folic acid (group II) only (p<0.01 for both groups). By contrast, although aggressive intervention with dietary folate (group III) or dietary advice (group IV) significantly increased intake of food folate (p<0.001 and p<0.05, respectively), there was no significant change in folate status. INTERPRETATION: We have shown that compared with supplements and fortified food, consumption of extra folate as natural food folate is relatively ineffective at increasing folate status. We believe that advice to women to consume folate-rich foods as a means to optimise folate status is misleading.

Lancet 1996 Mar 9;347(9002):657-9

Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study.

BACKGROUND: High intake of folate may reduce risk for colon cancer, but the dosage and duration relations and the impact of dietary compared with supplementary sources are not well understood. OBJECTIVE: To evaluate the relation between folate intake and incidence of colon cancer. DESIGN: Prospective cohort study. SETTING: 88,756 women from the Nurses' Health Study who were free of cancer in 1980 and provided updated assessments of diet, including multivitamin supplement use, from 1980 to 1994. PATIENTS: 442 women with new cases of colon cancer. MEASUREMENTS: Multivariate relative risk (RR) and 95% CIs for colon cancer in relation to energy-adjusted folate intake. RESULTS: Higher energy-adjusted folate intake in 1980 was related to a lower risk for colon cancer (RR, 0.69 [95% CI, 0.52 to 0.93] for intake > 400 microg/d compared with intake < or = 200 microg/d) after controlling for age; family history of colorectal cancer; aspirin use; smoking; body mass; physical activity; and intakes of red meat, alcohol, methionine, and fiber. When intake of vitamins A, C, D, and E and intake of calcium were also controlled for, results were similar. Women who used multivitamins containing folic acid had no benefit with respect to colon cancer after 4 years of use (RR, 1.02) and had only nonsignificant risk reductions after 5 to 9 (RR, 0.83) or 10 to 14 years of use (RR, 0.80). After 15 years of use, however, risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]), representing 15 instead of 68 new cases of colon cancer per 10,000 women 55 to 69 years of age. Folate from dietary sources alone was related to a modest reduction in risk for colon cancer, and the benefit of long-term multivitamin use was present across all levels of dietary intakes. CONCLUSIONS: Long-term use of multivitamins may substantially reduce risk for colon cancer. This effect may be related to the folic acid contained in multivitamins.

Ann Intern Med 1998 Oct 1;129(7):517-24

Plasma pyridoxal 5'-phosphate concentration and dietary vitamin B6 intake in free-living, low-income elderly people.

Free-living, elderly persons (aged greater than or equal to 60 y, n = 198) were recruited to determine the effects of age, sex, health status, dietary vitamin B6 intakes, and B6 supplement use on plasma pyridoxal 5'-phosphate (PLP). Vitamin B6 intakes were determined from 3-d diet records; supplementation was based on self-reported brand and frequency data. Fasting blood samples were analyzed for PLP. Subjects were primarily low-income Caucasians. There was no linear relationship between dietary vitamin B6 intake, age, sex or health status, and PLP while accounting for supplemental vitamin B6 use. PLP, however, was negatively correlated with age (p less than 0.001) in individuals with PLP values between 32 and 90 nmol/L. Vitamin B6 status was low (PLP less than 32 nmol/L) in 32% of this elderly population (n = 198) and could be attributed to low dietary vitamin B6 intakes and/or the presence of health problems reported to alter vitamin B6 status. This research suggests that low vitamin B6 status is prevalent in low-income, elderly persons, especially those with multiple health problems.

Am J Clin Nutr 1989 Aug;50(2):339-45

Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6) in healthy individuals. Oral doses of vitamin B6 reduce concentrations of serum folate.

Plasma total homocysteine response was compared in four groups of healthy individuals given orally divided doses of vitamin supplementations for a duration of 5 weeks. The vitamin supplements; A, 0.3 mg folic acid; B, 120 mg vitamin B6; C, combination of 0.3 mg folic acid and 120 mg vitamin B6 or D, 0.6 mg folic acid reduced the concentrations of plasma total homocysteine 20, 17, 32 and 24%, respectively. However, the intergroup comparisons did not show a significant difference in the effects of vitamin supplements. Multivariate analysis with correction for differences in pre-supplement values indicated a significant effect of vitamin B6 supplementation on plasma total homocysteine and serum folate. Our data show that plasma total homocysteine concentrations are reduced with low to medium divided doses of folic acid alone or in combination with vitamin B6.

Scand J Clin Lab Invest 1999 Apr;59(2):139-46

Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.

CONTEXT: Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available. OBJECTIVE: To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD. DESIGN: Prospective cohort study. SETTING AND PATIENTS: In 1980, a total of 80,082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6. MAIN OUTCOME MEASURE: Nonfatal MI and fatal CHD confirmed by World Health Organization criteria. RESULTS: During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58). CONCLUSION: These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

JAMA 1998 Feb 4;279(5):359-64

Age differences in vitamin B6 status of 617 men.

The effect of age on vitamin B6 metabolism was studied in 617 community-dwelling subjects, ages 18 to 90. These are, for the most part, clinically healthy, educated men whose intake of nutrients is not limited by economic factors. Plasma pyridoxal phosphate (PLP) was used as the primary criterion of vitamin B6 status. About one-third of the subjects were taking supplementary vitamins on their own initiative. The amount of pyridoxine-HCl varied from 0.1 to 105 mg/day. The average plasma PLP of the men not taking a supplement (N = 414) was 12.3 +/-0.3 ng/ml, with 25% of the values below 7.5 ng/ml and 7% below 5 ng/ml. There was a statistically significant decrease in plasma PLP with age of 0.9 ng/ml per decade. For those taking a supplement, the average plasma PLP was 20.5 +/- 1.0 ng/ml, with only 8% of the values below 7.5 ng/ml and none below 5 ng/ml. Glutamic-oxaloacetic transaminase activity in plasma (PGOT) and erythrocytes (EGOT) was determined on all subjects. The ratio of EGOT with in vitro stimulation by PLP to EGOT actual (alpha-EGOT) was also studied. These studies provide the most extensive normative data on vitamin B6 status available on men in the adult years of life.

Am J Clin Nutr 1976 Aug;29(8):847-53

Dietary sources of nutrients among US adults, 1989 to 1991.

OBJECTIVE: To identify major food sources of 27 nutrients and dietary constituents for US adults. DESIGN: Single 24-hour dietary recalls were used to assess intakes. From 3,970 individual foods reported, 112 groups were created on the basis of similarities in nutrient content or use. Food mixtures were disaggregated using the US Department of Agriculture (USDA) food grouping system. SUBJECTS/SETTING: A nationally representative sample of adults aged 19 years or older (n = 10,638) from USDA's 1989-91 Continuing Survey of Food Intakes by Individuals. ANALYSES PERFORMED: For each of 27 dietary components, the contribution of each food group to intake was obtained by summing the amount provided by the food group for all respondents and dividing by total intake from all food groups for all respondents. RESULTS: This article updates previous work and is, to the authors' knowledge the first to provide such data for carotenes, vitamin B12, magnesium, and copper. Beef, yeast bread, poultry, cheese, and milk were among the top 10 sources of energy, fat, and protein. The following other major sources also contributed more than 2% to energy intakes: carbohydrate: yeast bread, soft drinks/soda, cakes/cookies/, quick breads/doughnuts, sugars/syrups/jams, potatoes (white), ready-to-eat cereal, and pasta; protein: pasta; and fat: margarine, salad dressings/mayonnaise, and cakes/ cookies/quick breads/doughnuts. Ready-to-eat cereals, primarily because of fortification, were among the top 10 food sources for 18 of 27 nutrients. APPLICATIONS/CONCLUSIONS: These analyses are the most current regarding food sources of nutrients and, because of disaggregation of mixtures, provide a truer picture of contributions of each food group.

J Am Diet Assoc 1998 May;98(5):537-47

Folate intake and food sources in the US population.

Dietary data from 24-h recalls collected in the Second National Health and Nutrition Examination Survey (NHANES II) were analyzed to determine intake and food sources of folate in US adults between ages 19 and 74 y. Mean daily folate intake was 242 +/- 2.8 micrograms (means +/- SEM) for all adults, 281 +/- 3.6 micrograms for males, and 207 +/- 2.9 micrograms for females. Daily intake per 1000 kcal was 130 +/- 1.3 micrograms for all adults 122 +/- 1.3 micrograms for males, and 137 +/- 1.7 micrograms for females. Based on the Recommended Dietary Allowance of 400 micrograms/d, our results suggest that folate intake in the United States is low, particularly among women and blacks. Intake by age, education, and poverty index is discussed. Orange juice, white breads, dried beans, green salad, and ready-to-eat breakfast cereals are the major food sources of folate on a given day, contributing 37% of total folate intake.

Am J Clin Nutr 1989 Sep;50(3):508-16

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