Adjuvant Nutritional Intervention in Cancer (ANICA) was a clinical study carried out in Denmark in the 1990s with 32 typical patients with breast cancer, aged 32-81 yr and classified high risk because of tumor spread to the lymph nodes. The patients received standard therapy for their breast cancer, but got from the start additionally an adjuvant therapy in form of a cocktail consisting of vitamin C (2,850 mg/day), vitamin E (2,500 IU/day), beta-carotene (32.5 IU/day), selenium (Se; 387 micrograms/day), various other vitamins and essential trace elements, essential fatty acids (1.2 g gamma-linolenic acid/day and 3.5 g omega-3 PUFAs/day), and coenzyme Q10 (CoQ10, 90 mg/day). The protocol was later changed, with reduction of the Se intake and more coenzyme Q10 than when the study was started. The average survival of high-risk breast patients in the study was 50% after 5 yr, whereas for low-risk breast cancer patients (without metastases in the axilla when treatment was started), the average survival was 90% after ten years. The main investigator died, and the final report from the ANICA study was therefore never written. However, the published preliminary results from the trial were very promising; it seems, therefore, important to follow-up this study.
The anti-phlogistic effect of dietary vitamin E supplementation on the acute inflammation observed in experimental lens-induced uveitis in Brown Norway rats was studied. The effects of vitamin E were examined using histopathologic parameters as well as by measuring the levels of arachidonic acid metabolites. Histologic examination of the eyes revealed that the vitamin E-deficient animals had the most severe destruction of the retina, while those animals receiving the vitamin E-supplemented diet exhibited the best preservation of the retinal architecture. Levels of arachidonic acid metabolites, as determined by radioimmunoassay, were significantly higher in vitamin E deficient rats as compared with rats on a normal diet.
Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.
Dietary antioxidants such as vitamin E, vitamin C, beta carotene and flavonoids may retard atherosclerosis by preventing low density lipoprotein oxidation. Observational epidemiological studies, including ecological correlations, case control and prospective studies, indicate that high vitamin E levels may be associated with decreased cardiovascular disease. Beta carotene may be protective among smokers and the elderly. Few studies have been able to show that vitamin C has a protective effect. A handful of intervention studies have examined the effects of vitamin E and beta carotene with mixed results. While few side effects of antioxidant supplementation are known, the results of current, large-scale studies in primary intervention must be awaited before recommendations can be made. Increased intake of fruits and vegetables that are rich in antioxidants is recommended.
The Danish Fitness and Nutrition Council has evaluated the basis for recommendations on the intake of antioxidants and has found limited basis for increasing the recommended intake levels for the antioxidants vitamin C and E. Evidence was insufficient to support recommendations for polyphenol or carotenoid supplementation. Supplementation with high doses of vitamin E and beta-carotene may present a health risk. A high intake of fruit and vegetables is associated with a reduced risk of lifestyle diseases, but there is no evidence that this association is due to an antioxidant effect.
Comment In: Ugeskr Laeger. 2006 Oct 9;168(41):3537; author reply 353717066533
The aim of the study was to assess the relationships between individual-level dietary intakes of antioxidant vitamins C, E and beta-carotene with all-cause and cause-specific mortality in three Central and Eastern European (CEE) populations.
Data from the Health, Alcohol and Psychosocial factors in Eastern Europe cohort study were used. At the baseline survey, between 2002 and 2005, 28,945 men and women aged 45-69 years were examined in Novosibirsk (Russia), Krakow (Poland) and seven Czech towns. Deaths in the cohorts were identified through mortality registers. Cox regression was used to estimate the association between vitamin consumption and all-cause, cardiovascular (CVD) disease and cancer mortality.
In multivariable-adjusted analyses, there were no clear inverse associations between antioxidant vitamin intakes and mortality, although in some groups, several hazard ratios (HRs) were significant. For example, in men, compared with the lowest quintile of vitamin C intake, all-cause mortality in the third and fourth quintiles was lower by 28 % (HR 0.72; 95 % CI 0.61-0.85) and by 20 % (HR 0.80; 95 % CI 0.68-0.95), respectively. CVD mortality was lower by 35 % (HR 0.65; 95 % CI 0.50-0.84) and by 23 % (HR 0.77; 95 % CI 0.59-0.99) in third and fourth quintile of vitamin C intake, respectively. In women, the third and fourth quintiles of dietary intake of vitamin E were associated with reduced risk of all-cause death by 33 % (HR 0.67; 95 % CI 0.53-0.84) and by 23 % (HR 0.77; 95 % CI 0.61-0.97), respectively. Consumption of vitamin C, vitamin E and beta-carotene was not related to CVD mortality in women and to cancer mortality in either gender.
This large prospective cohort study in CEE populations with low prevalence of vitamin supplementation did not find a strong, dose-response evidence for protective effects of antioxidant vitamin intake.
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The study aimed to reveal associations between dietary antioxidant vitamins and other personal characteristics.
Population based, cross sectional survey.
Twenty seven rural, industrial, and semiurban communities in six different regions of Finland.
Subjects included 5304 men and 4750 women aged 15 years or older, who were interviewed about their dietary habits at the baseline study of the Finnish Mobile Clinic Health Examination Survey, 1967-72.
Intakes of carotenoids and vitamins A, E, and C were estimated from dietary history interviews covering the subjects' food consumption in the preceding year. In older age groups intakes of all the vitamins studied were low. Occupation had a profound effect on dietary antioxidant vitamins: intakes were highest in white collar workers and lowest in farmers; those classified as service workers, industrial workers, or housewives came in between. Current smoking was inversely associated with dietary carotenoids and vitamin C, especially in men. The vitamin intakes of ex-smokers were equal to or even slightly higher than those of never smokers. Married men had higher intakes of carotenoids and vitamin C than men living alone. Body mass index was not an important determinant of the intake of antioxidant vitamins.
The associations of dietary antioxidant vitamins with sociodemographic characteristics and smoking were strong enough to exert a confounding or modifying effect in studies on diet and diseases.
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It was shown that creatinphosphokinase activity of blood serum might be used as a criterion for evaluating the level of sparsely distributed damage in myocardium as a result of adrenaline administration. The protective effect of vitamin E under adrenaline-induced myocarditis was studied. The best effect was obtained after triple intramuscular injection of vitamin E before administration of pathological agent. Intravenous injection of the preparation has no benefits over that of intramuscular way of administration. Preventive action of vitamin E shows functioning itself in an increase of the quantity and activity of ubiquinone--the component of electron transport chain in mitochondria.
Affiliations of authors: Cancer Prevention Program (ARK) and SWOG Statistical Center (AKD, CMT, PJG), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Epidemiology (ARK, GEG) and Department of Environmental Health (GEG), University of Washington, Seattle, WA; University of Missouri, Research Reactor Center, Columbia, MO (JSM); Harry S. Truman Memorial Veterans Hospital, Columbia, MO (JSM); Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX (IMT); Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA (FLM); Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (LMM, HLP); Moores Cancer Center, University of California San Diego, San Diego, CA (SML); Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH (EAK).
The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.
There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided.
Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (
Comment In: J Natl Cancer Inst. 2014 Mar;106(3):dju00524563520
Alzheimer patients (AD) are known to be at risk for malnutrition and their older spouses may also have nutritional problems. The aim of our study was to clarify the association of caregivers' sex on the nutrient intake of AD couples.
Our study uses the baseline data of a randomized nutritional trial exploring the effectiveness of nutrition intervention among home-dwelling AD patients.
The central AD register in Finland was used to recruit AD patients living with a spousal caregiver, 99 couples participated in our study.
Nutritional status was assessed using the Mini-Nutritional Assessment (MNA). Nutrient intakes for both AD patients and their spouses were calculated from 3-day food diaries.
The mean age of caregivers and AD spouses was 75.2 (SD 7.0) and 77.4 years (SD 5.6), respectively. According to the MNA, 40% of male and 52% of female AD spouses were at risk for malnutrition. Among male caregivers, the mean energy and protein intakes were 1605 kcal (SD 458) and 0.93 g/body kg (SD 0.30), whereas the respective figures for their female AD spouses were 1313 kcal (SD 340) and 0.86 g/body kg (SD 0.32), respectively. Among female caregivers, the mean energy and protein intakes were 1536 kcal (SD 402) and 1.00 g/body kg (SD 0.30), whereas the respective figures for their male AD spouses were 1897 kcal (SD 416) and 1.04 g/body kg (SD 0.30). The interaction between male caregiver sex and lower energy (p