Mg Of Beta-carotene Research Articles

Investigation of the growth and metastasis of malignant melanoma in a murine model: the role of supplemental vitamin A.

Vitamin A possesses both wound-healing and antitumor actions. Vitamin A-induced fibroplasia results in subsequent increased collagen production and deposition. This effect of vitamin A has been shown to result in the production of collagenous capsules around several murine breast and lung tumor systems. This tumor encapsulation process can potentially convert a systemic disease to a local one that can be easily treated by tumor excision. The goal of the present study was to determine whether supplemental vitamin A could promote the encapsulation of a murine melanoma. Sixty DBA/2J male mice were inoculated intracutaneously with 1 x 106 Cloudman S91 melanoma cells using a 30-gauge needle. The mice were divided into three groups: a control group, a pre-vitamin A group, and a post-vitamin A group. The control mice were fed a commercial chow containing 15,000 IU of vitamin A and 6.4 mg of beta-carotene per kilogram diet, considerably more than the National Research Council's recommended daily allowance of vitamin A for normal mice. The control diet was, therefore, not vitamin A-deficient. The pre-vitamin A mice were fed the basal chow supplemented with 150,000 IU of vitamin A per kilogram diet for 10 days before inoculation and for the remainder of the study. The post-vitamin A mice were fed the vitamin A-supplemented diet beginning on the day of inoculation and continuing for the remainder of the study. Sixty days after inoculation, tumor growth was assessed and the five mice remaining in each group were euthanized. Ventral skin at the site of inoculation was harvested for histologic assessment of local tumor growth and invasiveness. The liver and lungs of each of these mice were also harvested for histologic assessment of tumor metastasis. Sixty days after tumor inoculation, a 60 percent survival rate was observed in the control group as opposed to the vitamin A-supplemented animals, which demonstrated a 100 percent survival rate in both groups (n = 5 in each group). Decreased mean tumor size and gross tumor in most vitamin A-supplemented animals were statistically significant when compared with the control animals. The control animals had a mean tumor size of 26.1 mm, whereas the post-vitamin A group had a mean tumor size of 5.7 mm. One hundred percent of the control group exhibited tumor; one animal had distant metastases. The pre-vitamin A group did not exhibit any tumor growth, and the post-vitamin A group exhibited tumor growth in 40 percent of animals. Neither vitamin A-supplemented group showed any evidence of distant metastases. The animals supplemented with vitamin A demonstrated decreased tumor growth and metastasis. This in vivo model may indicate a potential prophylactic and therapeutic role for supplemental vitamin A in the treatment of malignant melanoma.

Supplementation with β-Carotene or a Similar Amount of Mixed Carotenoids Protects Humans from UV-Induced Erythema

Carotenoids are useful oral sun protectants, and supplementation with high doses of beta-carotene protects against UV-induced erythema formation. We compared the erythema-protective effect of beta-carotene (24 mg/d from an algal source) to that of 24 mg/d of a carotenoid mix consisting of the three main dietary carotenoids, beta-carotene, lutein and lycopene (8 mg/d each). In a placebo-controlled, parallel study design, volunteers with skin type II (n = 12 in each group) received beta-carotene, the carotenoid mix or placebo for 12 wk. Carotenoid levels in serum and skin (palm of the hand), as well as erythema intensity before and 24 h after irradiation with a solar light simulator were measured at baseline and after 6 and 12 wk of treatment. Serum beta-carotene concentration increased three- to fourfold (P < 0.001) in the beta-carotene group, whereas in the mixed carotenoid group, the serum concentration of each of the three carotenoids increased one- to threefold (P < 0.001). No changes occurred in the control group. The intake of either beta-carotene or a mixture of carotenoids similarly increased total carotenoids in skin from wk 0 to wk 12. No changes in total carotenoids in skin occurred in the control group. The intensity of erythema 24 h after irradiation was diminished in both groups that received carotenoids and was significantly lower than baseline after 12 wk of supplementation. Long-term supplementation for 12 wk with 24 mg/d of a carotenoid mix supplying similar amounts of beta-carotene, lutein and lycopene ameliorates UV-induced erythema in humans; the effect is comparable to daily treatment with 24 mg of beta-carotene alone.

Inhibition of immunoglobulin E production in allergic model mice by supplementation with vitamin E and beta-carotene.

A diet containing different amounts of vitamin E (alpha-tocopherol; 0.5 mg, 5 mg, 10 mg or 50 mg per 100 g diet) was supplemented to BALB/c mice for 6 weeks. These mice were subcutaneously immunized twice with ovalbumin (OVA). A passive cutaneous anaphylaxis (PCA) analysis demonstrated that the mice fed on the diet containing 5 mg of vitamin E produced the highest level of the OVA-specific immunoglobulin E (IgE) antibody. A lower level of serum IgE was found in the mice supplemented with 0.5 mg, 10 mg and 50 mg of vitamin E. A sandwich ELISA analysis showed that the pattern of the total IgE antibody level among these four groups was the same as that of the allergen-specific IgE. In a separate experiment, 5 mg of vitamin E and/or 50 mg of beta-carotene was supplemented to the basal diet containing vitamin E as alpha-tocopherol acetate (5 mg) in order to evaluate the effect of their combination on OVA-specific and total IgE production in the mice. The supplementation with beta-carotene alone had no effect on OVA-specific or total IgE production. In contrast, supplementation with vitamin E plus beta-carotene effectively suppressed both the antigen-specific and total IgE antibodies. The serum vitamin E and beta-carotene levels were increased by supplementation with the respective compounds. These results strongly suggest that the combination of dietary vitamin E and beta-carotene suppressed IgE production and would therefore help to prevent the type-I allergic reaction.

Dietary β-Carotene Absorption by Blood Plasma and Leukocytes in Domestic Cats

Three experiments were conducted to study the uptake of oral beta-carotene by blood plasma and leukocytes in domestic cats. In Experiment 1, mature female Tabby cats (12 mo old) were given once orally 0, 10, 20 or 50 mg of beta-carotene and blood taken at 0, 12, 24, 30, 36, 42, 48 and 72 h after dosing. Concentrations of plasma beta-carotene increased in a dose-dependent manner. Peak concentrations were observed at 12-24 h and declined gradually thereafter. The half-life of plasma beta-carotene was 12-30 h. In Experiment 2, cats were dosed daily for six consecutive days with 0, 1, 2, 5 or 10 mg beta-carotene. Blood was sampled once daily at 12 h after each feeding. Daily dosing of cats with beta-carotene for 6 d resulted in a dose-dependent increase in circulating beta-carotene. Experiment 3 was designed to study the uptake of beta-carotene by blood leukocytes. Cats were fed 0, 5 or 10 mg of beta-carotene daily for 14 d. Blood leukocytes were obtained on d 7 and 14 to determine beta-carotene content in whole lymphocytes and in subcellular fractions. Blood lymphocytes took up large amounts of beta-carotene by d 7 of feeding. Furthermore, beta-carotene accumulated mainly in the mitochondria (40-52%), with lower amounts accumulating in the microsomes (20-35%), cytosol (15-34%), and nuclei (1.5-6%). Therefore, domestic cats readily absorb beta-carotene across the intestinal mucosa and transfer the beta-carotene into peripheral blood leukocytes and their subcellular organelles. beta-Carotene uptake kinetics show that some aspects of beta-carotene absorption and metabolism in cats are similar to those of humans.

Effects of dietary antioxidant supplementation on oxidative damage and resistance to oxidative damage during prolonged exercise in sled dogs.

To determine effects of dietary antioxidant supplementation on plasma concentrations of antioxidants, exercise-induced oxidative damage, and resistance to oxidative damage during exercise in Alaskan sled dogs. 62 Alaskan sled dogs. Dogs were matched for age, sex, and ability and assigned to 1 of 3 groups: sedentary and nonsupplemented (control [C]; n = 21), exercised and supplemented (S; 22), and exercised and nonsupplemented (N; 19). Dogs in group S were given 400 units of alpha-tocopherol acetate, 3 mg of beta-carotene, and 20 mg of lutein orally per day for 1 month, then dogs in groups S and N completed 3 days of exercise. Blood samples were collected before and after 1 and 3 days of exercise and after 3 days of rest. Plasma antioxidant concentrations were determined, and oxidative damage to DNA (plasma 7,8 dihydro-8-oxo-2'deoxyguanosine [8-oxodG] concentration) and membrane lipids (plasma hydroperoxide concentration) and resistance of plasma lipoproteins to oxidation were assessed. Supplementation increased plasma concentrations of alpha-tocopherol, beta-carotene, and lutein. Plasma concentration of alpha-tocopherol increased and concentration of lutein decreased in group S with exercise. Concentration of 8-oxodG decreased in group S but increased in group N during and after exercise. Lag time of in vitro oxidation of lipoprotein particles increased with exercise in group S only. Dietary supplementation with antioxidants resulted in increased plasma concentrations of antioxidants. Moreover, supplementation decreased DNA oxidation and increased resistance of lipoprotein particles to in vitro oxidation. Antioxidant supplementation of sled dogs may attenuate exercise-induced oxidative damage.

Dietary β-Carotene Stimulates Cell-Mediated and Humoral Immune Response in Dogs

The role of beta-carotene on immune response in domestic dogs is not known. Female Beagle dogs were fed 0, 2, 20 or 50 mg beta-carotene/d; blood was sampled at wk 0, 1, 2, 4 and 8 for analysis of the following: lymphoproliferation, leukocyte subpopulations and concentrations of interleukin-2 (IL-2), immunoglobulin (Ig)G and IgM. Delayed-type hypersensitivity (DTH) response was assessed at wk 0, 3 and 7. beta-Carotene supplementation increased plasma beta-carotene concentrations in a dose-dependent manner. Compared with unsupplemented dogs, those fed 20 or 50 mg of beta-carotene had higher CD4+ cell numbers and CD4:CD8 ratio. However, there was no treatment difference in CD8+, CD21+ and major histocompatability complex (MHC) class II+ cells. Plasma IgG, but not IgM concentration was higher in dogs fed beta-carotene throughout the study period. The DTH response to phytohemagglutinin (PHA) and vaccine was heightened in beta-carotene-supplemented dogs. beta-Carotene feeding did not influence mitogen-induced lymphocyte proliferation or IL-2 production. Immune response was impaired in dogs classified as low beta-carotene absorbers compared with similar dogs fed the same amount of beta-carotene. Therefore, dietary beta-carotene heightened cell-mediated and humoral immune responses in dogs.

Dietary β-Carotene Is Taken up by Blood Plasma and Leukocytes in Dogs

beta-Carotene uptake by blood plasma and leukocytes was studied in mature beagle dogs. In expt. 1, dogs were fed once orally with 0, 50, 100 or 200 mg of beta-carotene and their blood was sampled at 0, 1. 5, 3, 6, 10, 18 and 24 h. Plasma beta-carotene concentrations increased dose-dependently to peak at 6 h postfeeding. Concentrations decreased rapidly thereafter, showing a half-life of 3 to 4 h. In expt. 2, dogs were given daily doses for seven consecutive days with 0, 12.5, 25, 50 or 100 mg beta-carotene. Plasma beta-carotene concentrations increased dose-dependently; concentrations after the last dose were two- to fourfold higher than after the first dose. In expt. 3, dogs were fed 0, 50 or 100 mg beta-carotene daily for 30 d. beta-Carotene was elevated in lymphocytes and neutrophils in supplemented dogs. Furthermore, beta-carotene was taken up by the cytosol, mitochondria, microsomes (lymphocytes and neutrophils) and nuclei (lymphocytes only), proving that dogs can absorb beta-carotene. beta-Carotene is taken up by subcellular organelles of blood lymphocytes and neutrophils and in the plasma and leukocytes beta-carotene may have physiological importance as it relates to immunity in dogs. Uptake kinetics indicated that dogs are not an appropriate animal model for studying beta-carotene absorption and metabolism in humans.

Beta-carotene uptake and changes in ovarian steroids and uterine proteins during the estrous cycle in the canine.

The uptake of beta-carotene by reproductive tissues and the effects of beta-carotene on reproductive function in the dog are unknown. We studied the uptake of beta-carotene by blood, corpus luteum, and uterine endometrium and the role of dietary beta-carotene in influencing ovarian steroid and uterine protein production during the estrous cycle in the dog. Mature female Beagle dogs (n = 56) were fed diets containing 0, 2, 20, or 50 mg of beta-carotene daily for approximately 6 wk before estrus detection. Blood was sampled at regular intervals from estrus through d 45 after ovulation (d 0 = ovulation), when laparotomy was performed. The ovaries were obtained for the isolation of corpus luteum. The uterus was flushed with phosphate-buffered saline and the endometrium obtained by scraping. Beta-carotene was not detectable in plasma, corpus luteum, or endometrium of unsupplemented dogs. However, beta-carotene and alpha-carotene in plasma, corpus luteum, and uterine endometrium increased in a dose-dependent manner. Alpha-carotene made up a high percentage of total carotenoids even though the alpha-carotene content in the dietary source was very low. Dogs fed 50 mg of beta-carotene had significantly higher concentrations of plasma progesterone between d 12 and 26 compared with unsupplemented dogs. Dietary beta-carotene did not influence plasma estradiol-17beta and total uterine proteins. Therefore, beta-carotene is absorbed into plasma, corpus luteum, and uterine endometrium of dogs. Furthermore, dietary beta-carotene increased plasma progesterone concentrations during the estrous cycle. It is possible that dietary beta-carotene may improve reproductive function in the canine.

Antioxidant Nutrient Supplementation Reduces the Susceptibility of Low Density Lipoprotein to Oxidation in Patients With Coronary Artery Disease

Objectives. This study sought to determine the effect of antioxidant supplementation on the susceptibility of low density lipoprotein (LDL) to oxidation in patients with established cardiovascular disease (CVD).Background. Data are inconsistent regarding the role of antioxidant nutrients in the prevention of CVD.Methods. The study design was a 12-week, double-blind, placebo-controlled clinical trial. Patients with CVD (n = 45) were randomized to 1) placebo control; 2) 400 IU of vitamin E, 500 mg of vitamin C, 12 mg of beta-carotene (mid-dose); or 3) 800 IU of vitamin E, 1,000 mg of vitamin C, 24 mg of beta-carotene (high dose) daily. Reduced susceptibility of LDL to oxidation was estimated by an increase in lag phase (minutes). Baseline and 6- and 12-week measurements of lipoproteins and lag phase were obtained. Plasma levels of antioxidants were measured at baseline and 12 weeks.Results. Concentrations of alpha-tocopherol, vitamin C and beta-carotene significantly increased in the mid- and high dose groups during the trial. Lag phase significantly increased from baseline (190.1 ± 63.8 min [mean ± SD]) to 12 weeks (391.1 ± 153.0 min) in the high dose group (p < 0.01). A nonsignificant increase in lag phase in the mid-dose group was observed during the same time interval. A dose response was found for mean percent change from baseline to 12 weeks for lag phase for the placebo, mid- and high dose groups (p = 0.004 for trend).Conclusions. A high dose combination of antioxidant nutrients reduces the susceptibility of LDL to oxidation in patients with CVD and may be useful in secondary prevention.

Evidence for antioxidant nutrients‐induced pigmentation in skin: Results of a clinical trial

The aim of this study was to demonstrate that modification of the cellular redox-equilibrium occurs as a consequence of antioxidant nutrients intake (carotenoids, vitamine E and vitamine C) and that these nutrients play a role in the pigmentation of the skin without any UV exposure. We conducted a randomized, double-blind study in 20 healthy subjects to evaluate and to compare the efficacy of two mixtures of dietary antioxidants with regard to direct determination of melanin and carotenes by chromametry at selected skin sites and multiple reflection spectrometry from a 1 cm2 region of skin of different parts of the body. Efficacy was assessed by a significant improvement of these parameters, in comparison with measurements performed on the day of randomization, before dietary supplement intake. The formulations per capsule of study dietary supplements are: 13 mg of beta-carotene, 2 mg of lycopene, 5 mg of vitamine E and 30 mg of vitamine C (B13/L2) or 3 mg of beta-carotene, 3 mg of lycopene, 5 mg of vitamine E and 30 mg of vitamine C (B3/L3). A 8-week B13/L2-supplementation lead to a detectable carotenodermia whereas the B3/L3-supplementation not. Signicative increase of melanin concentrations in skin were found after 4, 5, 6 and 8 weeks of dietary antioxidant intake in both groups (p < 0.05). These results are discussed with regard to the redox control theory of melanocytes which regulates the tyrosinase activity.

Effects of Vitamin A Supplementation on Viral Load in HIV-1-Infected Pregnant Women

The World Health Organization recommends high-dose vitamin A administration to lactating women in the first 8 postpartum weeks to improve infant nutritional status. Of concern however are reports suggesting that vitamin A supplementation in women infected with HIV-1 may increase the viral load thereby accelerating disease progression and transmission. To investigate this issue plasma samples were obtained from 24 HIV-infected women delivering at King Edward Hospital in Durban South Africa at the time of delivery and 1 week later. Women were enrolled in the study at 28-32 weeks of pregnancy and administered either 5000 IU of retinyl palmitate and 30 mg of beta-carotene (12 women) or a placebo (12 women) until delivery and 200000 IU of retinyl palmitate at delivery to boost the vitamin A content of breast milk. At delivery both the HIV viral load and the mean absolute CD4 counts were lower--but not significantly--in the vitamin A-treated group. A week after vitamin A treatment at delivery there was no increase in viral load in the treatment group but this parameter increased significantly (p = 0.02) in the placebo group. The mean change in viral load was not statistically different between groups however. These preliminary findings confirm the advisability of continuing vitamin A intervention trials to reduce vertical transmission of HIV-1 in developing countries.

Retention and storage stability of beta-carotene in dehydrated drumstick leaves (Moringa oleifera)

Drumstick leaves (Moringa oleifera) procured from home gardens were shade dried after steam blanching or after steam blanching followed by sulphiting in 0.2% potassium metabisulphite solution and were stored in polythene containers having double lids for three months. The samples were analyzed for total carotene, beta-carotene and ascorbic acid in the fresh form, immediately after drying and on 30, 60 and 90 days of storage. Analysis of fresh leaves revealed that they contained 27.1 mg of total carotene, 17.4 mg of beta-carotene, and 143.6 mg of ascorbic acid per 100 g. Sulphiting in addition to blanching was more effective in the retention of beta-carotene immediately after dehydration (72% vs. 59%) and at the end of one month of storage (64% vs. 51%) but not at the end of 90 days of storage (53% vs. 47%). The shade-dried drumstick leaves when rehydrated and incorporated into recipes suffered further losses of beta-carotene, which were smaller in recipes that involved steaming and shallow frying (27% and 31%) but greater in recipes that involved repeated boiling and stirring (65%). All recipes were rated as highly acceptable and two of them per one serving provided the full RDA for pre-school children. Thus dehydrated drumstick leaves have the potential to serve as a valuable source of beta-carotene in the diets of the population in India and other developing countries.

Influence of antioxidants on the quality of stored blood.

Blood is exposed to oxidation stress and therefore has a high antioxidant capacity (AOC). With the many factors increasing the demands on the AOC, there may be damage to erythrocytes by free radicals. This study was to investigate evidence of erythrocyte damage in stored donor blood and to affect this by premedication of blood donors. Blood samples of 15 healthy donors were collected in CPDA-1 solution and analyzed immediately, and then again after 10 days of incubation at 4 degrees C and 1 day of incubation at 37 degrees C. Prior to incubation, the following parameters were evaluated: Na+, K+, malondialdehyde (MDA), hemoglobin (Hb), AOC in the supernatant, superoxide dismutase (SOD) in erythrocytes, and glutathione peroxidase (GSHPx) in whole blood. Blood donors of group 1 were not given any drugs or vitamins before blood sampling. The same blood donors were then supplemented with the following daily doses of antioxidants for 10 days before the next blood sampling: 36 mg of beta-carotene, 300 mg of vitamin E, 200 mg of vitamin C, and 40 mg of selenium. The blood from donors of group 2 had a significantly smaller increase in MDA, K+, and Hb, and a smaller decrease in Na+ and AOC in the supernatant compared with that of group 1, while the activity of SOD and GSHPx did not change during blood storage. These results suggest that antioxidants given to blood donors can improve red cell storage parameters by reducing cell damage caused by free radicals.

Barrett's esophagus: ordering the events that lead to cancer.

Reid, B J1,2,3; Barrett, M T1; Galipeau, PC1; Sanchez, C A1; Neshat, K2; Cowan, D S1; Levine, D S2 Author Information

Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease

Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Performance of young calves supplemented with vitamins C and E and beta-carotene (1996)

Newborn Holstein calves were used to investigate responses to supplemental antioxidants provided in daily milk allotments. Treated calves assigned to receive daily 100 IU of d-α tocopherol (vitamin E), 5 mg of beta-carotene, and 500 mg of ascorbic acid (vitamin C) in a 5-ml carrier. Control calves received the carrier alone. Additional vitamins C and E and beta carotene did not affect weaning age, weekly or total body weight gain, or dry feed intake. Supplementation of these antioxidants affected bull and heifer calves scour scores differently at different birth weights. Antioxidant supplementation increased the severity of scours during the first week for bull and heifer calves and the second week for bull calves but decreased the severity for heifer calves during the second week.; Dairy Day, 1996, Kansas State University, Manhattan, KS, 1996

Effect of beta-carotene supplementation on the concentrations and distribution of carotenoids, vitamin E, vitamin A, and cholesterol in plasma lipoprotein and non-lipoprotein fractions in healthy older women.

We studied the effect of beta-carotene supplementation on the concentrations and distribution in plasma lipoprotein and non-lipoprotein fractions of carotenoids, alpha-tocopherol, retinol, and cholesterol. Ten women ingested either 90 mg of beta-carotene or placebo daily for 3 weeks while residing in their homes and eating their usual meals. Carotenoids (beta-carotene, lycopene, lutein/zeaxanthin), retinol, alpha-tocopherol, and cholesterol were measured in plasma lipoprotein and non-lipoprotein fractions before and after treatment. In the beta-carotene-supplemented group, total plasma beta-carotene increased 14-fold from 0.48 +/- 0.13 to 6.83 +/- 2.12 mumol/L (p = 0.04). Although the greatest increase in beta-carotene was in low-density-lipoproteins (LDL), the magnitude of increase was similar in LDL, high-density-lipoproteins (HDL), and very-low-density-lipoproteins (VLDL). Thus, the relative distribution of beta-carotene in lipoproteins was unchanged: approximately 71% was in LDL, approximately 15% in HDL and approximately 12% in VLDL, before and after beta-carotene supplementation. There were no changes in amounts and distribution in lipoproteins of the other carotenoids, alpha-tocopherol, and cholesterol. There was no change in the amount of retinol in lipoprotein-deficient plasma. There were no changes in total plasma triglycerides. Significant positive correlations were found between LDL- or VLDL-cholesterol and alpha-tocopherol in LDL or VLDL, respectively; between LDL- or VLDL-cholesterol and lutein/zeaxanthin in LDL or VLDL, respectively; and between HDL-cholesterol and beta-carotene in HDL. beta-Carotene supplementation (90 mg/day for 3 weeks) in healthy older women results in an enrichment of all plasma lipoprotein fractions with beta-carotene, but does not alter the relative distribution of beta-carotene in lipoproteins. beta-Carotene supplementation has no effect on the amounts and relative distribution of lycopene, lutein/zeaxanthin, and alpha-tocopherol in lipoproteins, or of retinol in the non-lipoprotein fraction of plasma. Short-term beta-carotene supplementation has no effect on the concentrations of plasma total triglycerides, total cholesterol, HDL-, LDL-, and VLDL-cholesterol.

Relations between antioxidant vitamins in adipose tissue, plasma, and diet.

For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of beta-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of beta-carotene, retinol, and alpha-tocopherol, respectively. Data were collected in 1992 in the Netherlands for 85 healthy, nonsmoking volunteers aged 50-70 years (38 males and 47 females). For alpha-tocopherol, a significant age- and sex-adjusted partial correlation (r = 0.24, p < 0.05) was observed between adipose tissue levels and intake. For beta-carotene, the partial r was 0.20. Adipose tissue retinol did not reflect intake (partial r = 0.08). Correlations of adipose tissue vitamin levels with plasma vitamin levels were higher overall (r = 0.34 for alpha-tocopherol, r = 0.56 for beta-carotene, and r = 0.17 for retinol) than correlations with intake. Plasma concentrations of alpha-tocopherol, beta-carotene, and retinol were not associated with dietary intake (partial r's were 0.05, 0.17, and -0.12, respectively). Pearson correlations of repeated measurements in adipose tissue (after 4 months) were 0.24 for retinol, 0.50 for beta-carotene, and 0.78 for alpha-tocopherol. Adipose tissue beta-carotene was shown to increase sixfold after 6 months' supplementation with 30 mg of beta-carotene daily. It is concluded that adipose tissue vitamin concentrations are an acceptable alternative to plasma levels as relatively stable indicators of dietary intake. However, both plasma and adipose tissue levels are more useful as markers of internal dose, taking into account variations in absorption and metabolism, than of dietary intake.

Migraine and Subsequent Risk of Stroke in the Physicians' Health Study

To evaluate, in a prospective design, whether migraine is an independent risk factor for subsequent stroke. Evaluated as part of the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer begun in 1982. The aspirin component of the study was terminated in 1988, with average follow-up of 60.2 months. Conducted by mail among male physicians throughout the United States. A total of 22,071 US male physicians aged 40 to 84 years in 1982 with no prior history of cancer or cardiovascular diseases who were enrolled in the Physicians' Health Study. Participants were randomized to receive 325 mg of aspirin or aspirin placebo every other day and to receive 50 mg of beta-carotene or placebo on alternate days. The primary outcomes of the Physicians' Health Study were cardiovascular disease and cancer. Because stroke was a main outcome, this provided the opportunity to evaluate the association between migraine headaches and stroke. Physicians reporting migraine (n = 1479) had significantly increased risks of subsequent total stroke and ischemic stroke compared with those not reporting migraine. After adjustment for age, aspirin and beta-carotene treatment assignment, and a number of cardiovascular risk factors, the relative risks were 1.84 (95% confidence interval, 1.06 to 3.20) for total stroke and 2.00 (95% confidence interval, 1.10 to 3.64) for ischemic stroke. There were too few hemorrhagic strokes in the study to evaluate this end point. No associations were seen between ordinary nonmigraine headache and subsequent stroke or between migraine and subsequent myocardial infarction or cardiovascular death. These data raise the possibility that vascular events associated with migraine may also have causative importance in stroke but require confirmation in other studies specifically designed to evaluate this question.

A clinical trial of antioxidant supplements in the treatment of oral leukoplakia

Seventy-nine patients with oral leukoplakia that was histologically verified as either hyperkeratosis or epithelial dysplasia with hyperkeratosis were enrolled in an antioxidant supplementation program for the treatment of the oral lesions. The patients received 30 mg of beta-carotene, 1000 mg of ascorbic acid, and 800 IU of alpha-tocopherol per day for 9 months. Clinical improvement of the oral lesion was noted in 55.7% of the patients and was more likely to occur in patients who reduced their use of alcohol or tobacco ( p = 0.0056). Although risk-factor reduction was important, approximately half of the patients who did not alter their exposure to either alcohol or tobacco showed clinical improvement. The antioxidant supplementation significantly increased serum and tissue levels of beta-carotene, ascorbic acid, and alpha-tocopherol, but these changes did not correlate strongly with clinical improvement.