Randomized, placebo-controlled trial of dietary supplementation of alpha-tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial.

We evaluated the effects of vitamin E (dl-alpha-tocopherol) on mutagen sensitivity levels in a randomized placebo-controlled pilot trial. In brief, a dietary supplement of 1000 mg/day vitamin E or a placebo was randomly administered for 3 months to melanoma outpatients clinically free of the disease. Plasma vitamin E and mutagen sensitivity levels were measured at baseline and at the end of the trial after 3 months. At baseline, we found no significant differences in plasma vitamin E and mutagen sensitivity levels between the two groups. We also measured dietary intake at baseline and found dietary vitamin E to be a poor predictor of plasma levels of vitamin E. After 3 months of supplementation, we found that plasma levels of alpha-tocopherol increased significantly (P = 0.0005) in the vitamin E compared to the placebo group. We also found a non-significant, but consistent decrease in plasma gamma-tocopherol concentrations in the vitamin E supplemented compared to the placebo group. We did not find any significant difference between the vitamin E and placebo groups in mutagen sensitivity levels either at baseline or after 3 months of supplementation. We conclude that short term vitamin E supplementation, although it causes increased blood levels of alpha-tocopherol, does not provide protection against bleomycin-induced chromosome damage.

Alpha-tocopherol dietary supplement decreases titers of antibody against 5-hydroxymethyl-2'-deoxyuridine (HMdU).

This study evaluated the effects of vitamin E (alpha-tocopherol) on oxidative DNA damage in a randomized double-blind Phase II chemoprevention trial. Oxidative DNA damage was measured by the level of auto-antibody (Ab) against 5-hydroxymethyl-2'-deoxyuridine (HMdU) in plasma. After the baseline screening, eligible subjects (n = 31; plasma samples from 28 subjects were available for this study) were randomized to receive 15, 60, or 200 mg of alpha-tocopherol per day for 28 days. Biomarkers were measured twice at baseline--on day 1 (visit 1) and day 3 (visit 2)--and twice after intervention--on day 17 (visit 3) and day 31 (visit 4). At baseline, there was a highly significant inverse correlation between anti-HMdU Ab titer and plasma vitamin E level (r = -0.53; P = 0.004; n = 28). Smoking did not affect baseline anti-HMdU Ab titer; however, anti-HMdU Ab titer levels at baseline were significantly lower in subjects with above-median (0.75 ounce/day) alcohol consumption (P = 0.008). No significant change in anti-HMdU Ab level occurred at either visit 3 or visit 4 for subjects on the lowest dose, 15 mg alpha-tocopherol per day. Subjects receiving 60 mg of alpha-tocopherol per day had a significant decrease in anti-HMdU Ab level at visits 3 and 4 compared with baseline (P = 0.049 and P = 0.02, respectively). However, subjects receiving the highest dose, 200 mg/day, had less consistent results: a significant decrease in anti-HMdU Ab level was seen at visit 4 (P = 0.04) but not at visit 3. Our results demonstrate an inverse relationship between alpha-tocopherol and anti-HMdU Abs in plasma; oxidative DNA damage can be modulated by short-term dietary supplementation of alpha-tocopherol in some subjects.

Diet and nasopharyngeal cancer in a low-risk population.

Asian studies have reported that risk of nasopharyngeal cancer (NPC) is increased in individuals who frequently consume salted fish, which contains high levels of N-nitroso compounds. As part of a collaborative, population-based, case-control study in the U.S., where the annual incidence of the disease is low, we investigated whether dietary intake of preformed nitrosamines or nitrosamine precursors, or of antioxidants including vitamin C and carotenoids, was associated with altered risk of NPC overall, or of specific histologic subtypes of disease. Cases (n = 133) identified at 5 population-based cancer registries and controls (n = 212) identified through random digit dialing completed a telephone interview and self-administered food frequency questionnaire. Dietary exposures were expressed as quartiles of intake, and odds ratios (ORs) calculated using the lowest quartile of intake as the reference category. Risk of non-keratinizing and undifferentiated tumors of the nasopharynx was increased in frequent consumers of preserved meats, which contain high levels of added nitrites. ORs in the 2nd, 3rd and highest quartile were 1.99, 4.35 and 4.59, although 95% confidence intervals did not exclude 1.0. Risk of differentiated squamous cell carcinoma, but not other histologic types, was significantly reduced in individuals with vitamin C intake above the lowest quartile (ORs 0.30, 0.33 and 0.30 in the 2nd, 3rd and highest quartiles, respectively). This association was markedly stronger among non-smokers and former smokers than among current smokers. Finally, individuals who reported consuming supplemental vitamins were at an approximately 50% reduced risk of NPC. Our results indicate that future studies should consider the effects of dietary risk factors on the risk of specific histologic subsets of NPC, and not assume that the disease is etiologically homogeneous.

Effects of dietary supplementation of alpha-tocopherol on plasma glutathione and DNA repair activities.

In a randomized double-blind trial of alpha-tocopherol (vitamin E), we investigated the effects of alpha-tocopherol supplementation on lipid- and water-soluble antioxidants in plasma and DNA repair activities in peripheral mononuclear leukocytes. Baseline levels of antioxidants and DNA repair activities were assessed twice before alpha-tocopherol intervention: on day 1 (visit 1) and day 3 (visit 2). During the second visit, participants were randomized to receive one of three dosages of alpha-tocopherol, 15, 60, or 200 mg/day for 4 weeks. The same biochemical measurements as at baseline were repeated twice after intervention: on day 17 (visit 3) and day 31 (visit 4). A total of 31 healthy volunteers were eligible for the study, completed all four visits and were included in the final data analysis. At baseline, no appreciable differences of dietary intake of vitamin E and plasma alpha-tocopherol were observed among the three dosage groups. In general, supplementation of alpha-tocopherol for 2-4 weeks resulted in a dose-dependent increase of plasma level of alpha-tocopherol (compared to baseline); significant increases of plasma alpha-tocopherol at visits 3 and 4 were observed in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. At visit 4 (but not visit 3), plasma glutathione levels were significantly elevated (compared to baseline) in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In addition, there was an increase in the lipid protection ratio by supplementation of alpha-tocopherol for 2-4 weeks in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In general, there were no consistent effects of alpha-tocopherol on DNA repair activities in peripheral mononuclear leukocytes after being adjusted for baseline DNA repair activities. Results from this study demonstrate the interrelationship between alpha-tocopherol and other antioxidants in plasma; total plasma antioxidants can be modulated by short-term dietary supplementation of alpha-tocopherol.

Assessment of exposure to indoor air contaminants from combustion sources: methodology and application.

A methodology for assessing indoor air pollutant exposures is presented, with specific application to unvented combustion by-products. This paper describes the method as applied to a study of acute respiratory illness associated with the use of unvented kerosene space heaters in 333 residences in the New Haven, Connecticut, area from September 1982 to April 1983. The protocol serves as a prototype for a nested design of exposure assessment which could be applied to large-scale field studies of indoor air contaminant levels. Questionnaires, secondary records, and several methods of air monitoring offer a reliable method of estimating environmental exposures for assessing associations with health effects at a reasonable cost. Indoor to outdoor ratios of NO2 concentrations were found to be 0.58 +/- 0.31 for residences without known sources of NO2. Levels of NO2 were found to be comparable for homes with a kerosene heater only and those with a gas cooking stove only. Homes with a kerosene heater and a gas stove had average two-week NO2 levels approximately double those with only one source. Presence of tobacco smokers had a small but significant impact on indoor NO2 levels. Two-week average levels of indoor NO2 were found to be excellent predictors of total personal NO2 exposure for a small sample of adults. Residences with kerosene space heaters had SO2 levels corresponding to the number of hours of heater use and the sulfur content of the fuel. Formaldehyde levels were found to be low and not related to unvented combustion sources. NO2, SO2, and CO2 levels measured in some of the residences were found to exceed those levels specified in current national health standards.