Dietary Β-carotene Research Articles

Effects of dietary beta-carotene on the immune response of rainbow trout Oncorhynchus mykiss

We attempt to assess the impact of different levels of dietary β-carotene on immune function in rainbow trout. Semi-purified diets containing 0, 40, 200, and 400 mg β-carotene/kg dry diet were fed for 12 weeks to fish with average weight of 45 g. In addition to the humoral and cellular immune parameters, growth and feed utilization were examined. There were no marked differences in growth and feed utilization showing that β-carotene was not particularly efficient in enhancing growth of rainbow trout. Of the immune parameters measured, total immunoglobulin was significantly highest for the 200 mg β-carotene fed group. Serum complement activity (alternate pathway) at 200 and 400 mg β-carotene supplementation was significantly higher than that of the unsupplemented group. An increasing trend in lysozyme activity was observed, however, the differences among the groups were not significant. Phagocytic activity was similar among diet groups except at the highest level of supplementation where it was the maximum. Oxygen radical production by peripheral blood leukocytes appeared to be lower at higher levels of carotenoid supplementation. Overall, dietary β-carotene clearly enhanced immune response parameters in rainbow trout such as serum complement activity and total plasma immunoglobulin but did not show a definite influence for the other factors examined in the present study.

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.

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.

β-Carotene Fails to Act as a Tumor Promoter, Induces RAR Expression, and Prevents Carcinoma Formation in a Two-Stage Model of Skin Carcinogenesis in Male Sencar Mice

Clinical trials have shown a significant increase in incidence of lung cancer among smokers and asbestos workers supplemented with β-carotene, suggesting a tumor- promoting activity for this agent. We set out to test possible tumor-promoting and chemopreventive activities of dietary and topical β-carotene in the two-stage 7,12-dimethylbenz[a]anthracene-12-O-tetradecanoylphorbol 13-acetate (TPA) model of mouse skin carcinogenesis. In the first study, the effects of three levels of dietary β-carotene (6, 60, and 600 μg/g purified diet containing no other retinoid or carotenoid) were assessed over a period of 42 weeks. Carcinoma yield was reduced by ∼50% in the 600 μg/g diet group (mean 0.22 carcinomas/mouse) compared with the 6 μg/g diet group (mean 0.44 carcinomas/mouse, p = 0.003). The 60 μg/g diet group showed a pattern of inhibition similar to the 600 μg/g diet group. A protective effect (25% reduction) of β-carotene (in the 600 μg/g diet group) on papilloma formation was also found. However, the intermediate 60 μg/g diet group showed the same incidence as the low 6 μg/g diet group. This points to a lack of correlation between papilloma and carcinoma incidence, as we also found in previous work on dietary retinoids and carotenoids. The purpose of the second study was to assess whether topical β-carotene (2 μg) has tumor-promoting or chemopreventive activity in the two-stage protocol. In the absence of TPA, β-carotene had no significant tumor-promoting activity. Instead, papilloma yield induced by TPA was decreased by topical β-carotene from an average of 20 to ∼10 papillomas/mouse (p = 2.5 ×10-7). The effect of topical β-carotene persisted beyond the treatment period (Week 24) until the termination of the study at Week 42. Western blot analysis of mouse skin extracts showed that topical β-carotene upregulated retinoic acid receptor-α and -γ expression in the dorsal skin. This finding suggests that β-carotene may work as a chemopreventive agent by upregulating the expression of retinoid receptors in mouse skin. In conclusion, our data show that β-carotene prevents skin carcinoma formation, induces retinoic acid receptor expression, and fails to act as a tumor promoter in the two-stage model of skin tumorigenesis.

Dietary Supplementation of a Natural Isomer Mixture of Beta-Carotene Inhibits Oxidation of LDL Derived from Patients with Diabetes mellitus

Background: Accelerated atherosclerosis is common in patients with diabetes mellitus which may be linked to increased lipid peroxidation. Therefore, we compared the oxidation of LDL derived from patients with diabetes to normoglycemic controls and followed-up the effect of dietary β-carotene supplementation on LDL oxidation. Methods: Twenty patients with long-standing non-insulin-dependent diabetes mellitus were studied in comparison with age- and sex-matched control subjects. Dunaliella bardawil-derived β-carotene was supplemented to the patients for 3 weeks, 60 mg daily dose. LDL oxidation was analyzed by measuring malondialdehyde (MDA), lipid peroxides (PD), and conjugated dienes (CD) generation in response to CuSO₄-induced oxidation. LDL lipid composition and the LDL associated vitamins A, E and carotenoids were also measured. Results: LDL susceptibility to oxidation by CuSO₄ was increased in the patients by 40% with a 35% shorter lag time required for the initiation of LDL oxidation, i.e. 56 ± 6 min in patients vs. 85 ± 9 min in controls (p <0.01). Patients showed increased cholesterol/phospholipid and polyunsaturated/saturated ratios, as well as reduced content of LDL associated vitamins. Upon β-carotene supplementation, there was a significant elevation in plasma and in LDL all-trans β-carotene [from 0.296 ± 0.020 to 0.968 ± 0.133 μg/mg LDL protein (p < 0.01)] paralleled by a significant reduction in LDL susceptibility to oxidation, as exhibited by increased lag time up to 115 ± 10 min (p < 0.01) and reduction in MDA and PD generation (by 25 and 40%), respectively (p < 0.01). Conclusions: Increased susceptibility to oxidation of LDL derived from patients with diabetes mellitus is associated with abnormal LDL lipid composition and antioxidant content. Natural β-carotene dietary supplementation normalizes the enhanced LDL oxidation and consequently may be of importance in delaying accelerated development of atherosclerosis in these patients.

Dietary β-carotene protects lung and liver parenchyma of rats treated with monocrotaline

Some studies have indicated that the injury induced by the hepato- and pneumotoxin monocrotaline (MCT) is in part mediated by oxidation. Because β-carotene is a potent antioxidant, we hypothesized that it would protect the lung and liver parenchyma against MCT-induced injury. Twenty rats were assigned randomly to four groups. All rats were fed a standard AIN93G diet with or without β-carotene. After 1 week on the purified diets, half of the rats fed the control (standard) diet and half of the rats fed the β-carotene-supplemented diet were injected subcutaneously with 60 mg MCT/kg body weight or its vehicle (water). All rats were sacrificed at 4 weeks. Histological examination showed that β-carotene alone did not affect lung or liver structure. On the other hand, lungs of MCT-treated rats had severe focal pneumonia, extensive deposition of collagen in the septa, marked inflammation of the small arteries and arterioles, and arterialization of the small venules. Livers of MCT-treated rats showed some fatty infiltration and diffuse hemorrhages, more prominent sometimes in the centrilobular area and sometimes in the periportal region. Concomitant treatment with β-carotene protected the lung parenchyma from the inflammatory reaction and the septal fibrosis, but did not prevent cardiac right ventricular hypertrophy and only slightly reduced the thickening of the wall of small arteries and arterioles. Incidence of steatosis and hemorrhages was decreased in the liver. These results indicate that MCT-induced pulmonary vascular remodeling occurs in the absence of inflammatory cell infiltration. Furthermore, β-carotene prevented inflammation and protected the lung and liver parenchyma of MCT-treated rats.

Effects of carotenoids on human immune function

Many epidemiological studies have shown an association between diets rich in carotenoids and a reduced incidence of many forms of cancer, and it has been suggested that the antioxidant properties of these compounds are a causative factor. Attention has focused on the potential role of one specific carotenoid, beta-carotene, in preventing cancer, and numerous publications have described in vitro experiments and animal studies which suggest that not only can this carotenoid protect against the development of cancer, but also several other chronic diseases. Since the immune system plays a major role in cancer prevention, it has been suggested that beta-carotene may enhance immune cell function. Several human trials, using dietary beta-carotene supplementation with a wide range of intakes, have been undertaken to address this hypothesis. The general conclusion of these studies is that this compound can enhance cell-mediated immune responses, particularly in the elderly. The present article will review some of these human studies and, hopefully, complement the reviews of other authors associated with the present symposium, some of whom will also describe work in this area. Potential mechanisms for the effects of carotenoids on immune function will also be reviewed. Finally, possible reasons for the failure of three major prospective studies to demonstrate a beneficial effect of beta-carotene supplementation on lung cancer risk will be discussed.

Dietary beta-carotene and alpha-tocopherol combination does not inhibit atherogenesis in an ApoE-deficient mouse model.

Although lipid oxidation plays a major role in atherogenesis, the role of antioxidants in the prevention and treatment of the process is not clear. Apolipoprotein (apo) E-deficient mice develop spontaneous atherosclerotic lesions in major arteries. The presence of oxidized lipoprotein epitopes in the lesion suggests that oxidation reactions are involved in atherogenesis in this mouse model, but the inhibitory effect of antioxidants on atherogenesis in the model is controversial. To test the effect of dietary antioxidants on atherogenesis, male apoE-deficient mice (n=15) were fed a standard chow diet supplemented with 0.05% alpha-tocopherol and 0.05% all-trans beta-carotene. A control group (n=15) received no antioxidant supplement. At the end of the trial, mice consuming vitamins had 5x more plasma vitamin E but undetectable beta-carotene levels. However, liver levels of the beta-carotene metabolite, retinyl palmitate, were higher in antioxidant-treated mice compared with control mice. The antioxidants had no effect on lipoprotein or on plasma anti-oxidatively modified low density lipoproteins (anti-oxLDL) antibody levels. The vitamins had a small but insignificant effect on lipoprotein resistance to ex vivo oxidation, determined by a longer lag period of conjugated diene formation. Atherosclerosis, determined by the lesion size at the aortic sinus, was insignificantly suppressed in antioxidant-treated mice (mean area+/-SE, 20 000+/-7129 versus 13 281+/-5861 micrometer(2); P=0.40). The aortic atherosclerotic lesion area was similar in both experimental groups (2.55+/-0.65% and 2.08+/-0.5% of total aortic area in the control and antioxidant group, respectively; P=0.58). The results of the current study suggest that moderate levels of synthetic antioxidant vitamins have no effect on atherogenesis in apoE-deficient mice.

Dietary supplementation with β-carotene, but not with lycopene, inhibits endothelial cell-mediated oxidation of low-density lipoprotein

Carotenoids may protect low-density lipoprotein from oxidation, a process implicated in the development of atherosclerosis. Our previous studies showed that in vitro enrichment of low-density lipoprotein (LDL) with β-carotene protected it from cell-mediated oxidation. However, in vitro enrichment with either lutein or lycopene actually enhanced oxidation of the LDL. In the present studies we have examined the impact of LDL carotenoid content on its oxidation by human aortic endothelial cells (EaHy-1) in culture, comparing the effects of in vivo supplementation with in vitro enrichments. The β-carotene content in human LDL was increased three- to sixfold by daily supplementation with 15 mg β-carotene for 4 weeks, and the lycopene content of LDL in other individuals was increased two- to threefold by ingestion of one glass (12 ounce) of tomato juice daily for 3 weeks. LDL isolated from these healthy, normolipidemic donors not taking supplemental carotenoid was incubated at 0.25 mg protein/ml with EaHy-1 cells in Ham’s F-10 medium for up to 48 h. Following dietary β-carotene supplementation, LDL oxidation (as assessed by formation of lipid hydroperoxides) was markedly inhibited, to an even greater extent than was observed for LDL enriched in vitro with β-carotene (that resulted in an 11- to 12-fold increase in LDL β-carotene). No effect on cell-mediated oxidation was observed, however, for LDL enriched in vivo with lycopene. Thus, β-carotene appears to function as an antioxidant in protecting LDL from cell-mediated oxidation although lycopene does not. The fact that the three- to sixfold enrichments of LDL with β-carotene achieved by dietary supplementation were more effective in inhibiting oxidation than the 11- to 12-fold enrichments achieved by an in vitro method suggests that dietary supplementation is a more appropriate procedure for studies involving the enrichment of lipoprotein with carotenoids.

Ferrets (Mustela putoius furo) Inefficiently Convert β-Carotene to Vitamin A 4-5

The ferret has recently been used as a model to evaluate the absorption and metabolism of several carotenoids; however, little is known about the vitamin A (VA) requirements of this species or the ability of ferrets to convert dietary β-carotene (βC) to VA. Three studies were conducted to estimate the daily utilization of VA in ferrets and to determine the effect of prior VA status on the ability of ferrets to utilize βC as a source of VA. Weanling male ferrets were fed a pelleted, low carotenoid, semipurified diet either with (+VA) or without VA (−VA) for 21- to 35-d prefeeding periods. Upon initiation of the experiments, several ferrets were killed to determine base-line VA status. The remaining ferrets were fed VA, βC, or VA and βC in pelleted feed (Studies 1–3) or liquid carrier (Study 3) for 16–21 additional days. Hepatic VA and βC concentrations were used as the primary indicators of VA status, although serum and adrenal VA and βC also were measured. The results showed the following: 1) provision of βC at up to a 15:1 weight ratio of βC to VA in pelleted feed or liquid carrier was not sufficient to maintain hepatic VA stores after a −VA prefeeding period; 2) the daily utilization rate of VA by ferrets ranged from 80 to 171 μg in the three studies; 3) the ferret was confirmed to be a species that has the majority of its serum VA in ester form; and 4) feeding −VA diets significantly reduced serum retinyl esters but had less effect on serum retinol. We conclude that although ferrets can convert βC to VA, the process is inefficient. The ferret model can be most appropriately used when studying the biological effect of tissue βC stores on VA status and is less appropriate for the evaluation of dietary βC conversion to VA.

Dietary β-carotene, but not lycopene, inhibits endothelial cell-mediated LDL oxidation: [formula omitted], D.W. Morel and E.H. Harrison. MCP-Hahnemann School of Medicine and University of the Sciences in Philadelphia, Philadelphia, PA

Dietary β-carotene, but not lycopene, inhibits endothelial cell-mediated LDL oxidation: [formula omitted], D.W. Morel and E.H. Harrison. MCP-Hahnemann School of Medicine and University of the Sciences in Philadelphia, Philadelphia, PA

Acquired risk factors and susceptibility to environmental toxicants

Susceptibility to illness after exposure to environmental toxicants is determined by the interaction of numerous factors involving both constitutive and acquired traits. Constitutive susceptibility (risk) factors are the intrinsic traits determined by developmental stage, gender, and genetic makeup. Within a population, changes in constitutive risk factors tend to occur slowly, through aging, alterations in the birth or death rate, or by migration in or out of the population. Often overlooked is the effect of acquired susceptibility factors on susceptibility to environmental toxicants. Acquired susceptibility factors, which are related to the effects of living conditions, psychosocial factors, diet, behavior and access to medical care, may modify the effect of constitutive factors. Three examples demonstrate the interaction of acquired susceptibility factors with exposure and constitutive factors. The increased prevalence of asthma in children is suspected of having a strong environmental component but the underlying acquired susceptibility factors, if any, are difficult to identify because of the multifactorial nature of asthma and the use of surrogate risk factors such as parent's education. β-Carotene is a dietary component which may modify acquired susceptibility. While numerous observational studies find that dietary β-carotene reduces the risk of lung cancer in cigarette smokers, intervention studies do not support this role. Hepatitis B is an example of an infectious agent functioning as an acquired susceptibility factor. Hepatitis B synergistically increases the risk of hepatocellular carcinoma when accompanied by exposure to aflatoxin, a relationship that may be modified by constitutive risk factors, such as epoxide hydrolase capabilities. Acquired risk factors have the potential to greatly influence risk and their impact should be included in future studies of the health effects of environmental toxicants.

The effect of β-carotene supplementation on the immune function of blood monocytes from healthy male nonsmokers

Although there is strong epidemiologic evidence that diets rich in carotenoids such as β-carotene are associated with a reduced incidence of cancer, the cellular mechanisms underlying this phenomenon remain unknown. This article describes the effect of dietary β-carotene supplementation on both the expression of functionally associated surface molecules on human monocytes and on the secretion of the cytokine tumor necrosis factor-α (TNF-α) by monocytes, all of which are involved in the initiation and regulation of immune responses involved in tumor surveillance. A double-blind, placebo-controlled, crossover study was undertaken in which 25 healthy, adult male nonsmokers were randomly assigned to receive β-carotene (15 mg daily) or placebo for 26 days, followed by the alternative treatment for a further 26 days. The expression of functionally related monocyte surface molecules was quantified by flow cytometry, and ex vivo secretion of TNF-α was quantified by an enzyme-linked immunosorbent assay, before and after each treatment period. After dietary supplementation there were significant increases in plasma levels of β-carotene and in the percentages of monocytes expressing the major histocompatibility complex class II molecule HLA-DR and the adhesion molecules intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. In addition, the ex vivo TNF-α secretion by blood monocytes was significantly increased after supplementation. These findings suggest that moderate increases in the dietary intake of β-carotene can enhance cell-mediated immune responses within a relatively short period of time, providing a potential mechanism for the anticarcinogenic properties attributed to β-carotene.

Synergistic suppression of azoxymethane-induced foci of colonic aberrant crypts by the combination of β-carotene and perilla oil in rats

The modulating effect of the combined dietary feeding of beta-carotene and perilla oil, which is rich in alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Rats received oral administration of beta-carotene (0, 50 or 200 mg/kg body weight/day) and fed a basal diet containing either 12% olive oil, 3% perilla oil plus 9% olive oil, or 12% perilla oil. A dose-dependent suppressive effect of perilla oil was found. The numbers of ACF were 42.0 and 18.4% of those of the 12% olive oil-fed controls in the rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. The development of ACF was also reduced significantly by the addition of dietary beta-carotene in each of the oil-fed groups (P < 0.05, respectively). The suppression by the combination of beta-carotene and perilla oil was synergistic, as the numbers of ACF were 12.9 and 8.9% of those of the 12% olive oil-fed controls in beta-carotene-treated rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. beta-carotene plus perilla oil also suppressed the numbers of silver-stained nucleolar organizer regions and the expression of ras mRNA in the colonic mucosa (cell proliferation biomarkers). Following administration of beta-carotene, a significant increase in the concentration of intact beta-carotene molecules was found in the colonic mucosa, livers, and sera. However, no accumulation of retinoids was observed in the colonic mucosa, suggesting that the inhibitory effect may not be related to the provitamin A activity. These results suggest that the combination of beta-carotene and perilla oil may be useful in the prevention of colon cancer.

Serum β-carotene response to supplementation with raw carrots, carrot juice or purified β-carotene in healthy non-smoking women

Epidemiological studies have shown that high intake of carotenoid-rich vegetables and fruits and high blood levels of β-carotene are associated with decreased risk of cancer. In western countries, carrot is the most important source of dietary β-carotene. In the present study, the serum response to chronic ingestion of β-carotene from raw carrots, carrot juice and capsules containing purified β-carotene was studied. The subjects were 38 healthy, non-smoking female volunteers, aged 20–53 years. They were instructed to consume low-carotenoid diets for 10 days before starting the supplementation and throughout the study. According to food frequency questionnaires, the average habitual intake of β-carotene was 4.5 mg/day, whereas the low-carotenoid diet provided only 0.4 mg/day. After the 10-day depletion period, the average serum β-carotene concentration fell to 53% of the habitual level. The participants were assigned into three groups with similar mean serum β-carotene concentrations. Each group was supplemented for 6 weeks with approximately 12 mg of β-carotene/day, either as raw carrots (120 g/day), carrot juice (1 dl/day) or β-carotene capsules (2 capsules/day). The increase in serum β-carotene level was determined after 3 and 6 weeks of supplementation. The mean serum β-carotene concentration increased significantly in all test groups, the response being greatest in the group receiving β-carotene capsules. No difference in the serum response between carrot and carrot juice was detected. However, there was a wide variation in the individual response of serum β-carotene to supplementation, regardless of the source. Variation was especially large — ranging from a lack of response to over 8-fold increase in the serum β-carotene concentration — in the group receiving β-carotene capsules. These data indicate that 1) serum response is lower after ingestion of natural β-carotene than after ingestion of purified β-carotene from capsules, and 2) equal intake of β-carotene, whether from carrot, carrot juice or capsules, elicits very different serum responses in different individuals.

Effects of dietary beta-carotene and selenium on initiation and promotion of pancreatic carcinogenesis in azaserine-treated rats.

In the present study the effects of 0.1 or 1.0 g beta-carotene/kg diet (L beta C or H beta C) and 1.0 mg or 2.5 mg selenium/kg diet (LSel or HSel), as well as combinations of the respective low and high concentrations of beta-carotene and selenium (LMix or HMix) on the initiation/early promotion phase or on the late promotion phase of pancreatic carcinogenesis in azaserine-treated rats, were investigated using cell proliferation and volumetric data of atypical acinar cell foci (AACF) as parameters. The present results indicate chemopreventive effects of dietary selenium, dietary beta-carotene and of their combination on the development of acinar pancreatic lesions induced in rats by azaserine. The inhibitory effect was most pronounced when beta-carotene and/or selenium were added to the diets during the late promotion phase of the carcinogenic process, although inhibition was also observed with these compounds when they were added to the diets during the first 5 weeks of the study only (initiation/early promotion phase). Neither in the initiation/early promotion phase nor in the late promotion phase was a dose-related trend observed. The multiplicities of AACF with a diameter over 1.0 mm and of carcinomas in situ (CIS), as well as the incidence of CIS were not significantly different among the groups. However, in the late promotion experiment a dose-related decline in multiplicity could be observed in the selenium supplemented groups and in the groups receiving combinations of beta-carotene and selenium. Cell proliferation in azaserine-induced AACF, as estimated by the bromodeoxyuridine (BrdU) labeling index, was significantly higher in H beta C, HSel, LMix and HMix groups (initiation/early promotion phase) as well as in H beta C, LSel, HSel, LMix and HMix groups (late promotion phase) than in high fat controls. From the present results it can be concluded that: (i) beta-carotene and selenium have inhibitory effects on pancreatic carcinogenesis induced in rats by azaserine; (ii) the most clear effects were observed when selenium was given as such, or in combination with beta-carotene during the late promotion phase; and (iii) beta-carotene and selenium stimulate cell proliferation in AACF.

Relationship of serum cholesterol, dietary and plasma β-carotene with lung cancer in male smokers

It has been hypothesized that beta-carotene mediates the association between low serum cholesterol levels and increased risk of lung cancer. It follows from this assumption that this association should be greater in population strata with a low intake of beta-carotene than in with those with a high intake. To investigate this hypothesis, we analysed dietary beta-carotene, plasma beta-carotene and serum cholesterol levels in 20 male smokers with lung cancer and 103 male smoking controls, a subsample taken from a larger case-control study on oxidant-antioxidant status. As predicted, we found that the association between low serum cholesterol levels and lung cancer risk was greater in subjects with low plasma beta-carotene. Controlling for plasma beta-carotene decreased but did not negate the magnitude of the inverse association between serum cholesterol and lung cancer. A low serum cholesterol level tended to increase the risk associated with low plasma beta-carotene. Our data suggest that a low plasma beta-carotene does not totally explain the association between serum cholesterol and lung cancer.

Effects of dietary β-carotene supplementation on nitroso-amine induced squamous cell carcinoma of the esophagus in rats

Effects of dietary β-carotene supplementation on nitroso-amine induced squamous cell carcinoma of the esophagus in rats

β-Carotene Supplementation Increases Antioxidant Capacity of Plasma in Older Women , ,

The antioxidant effect of dietary β-carotene supplementation on the peroxidation potential of plasma was investigated in a randomized double-blind, placebo-controlled study. Twelve healthy women (62–80 y) supplemented their usual daily diet with 90 mg of β-carotene (n = 6) or placebo (n = 6) capsules for 3 wk. Plasma concentrations of β-carotene, α- and γ-tocopherol, ascorbate, urate, bilirubin and in vitro production of phosphatidylcholine hydroperoxides (PC-OOH) and utilization of plasma antioxidants in the presence of 50 mmol/L 2,2′-azobis (2-aminopropane) hydrochloride (AAPH), a free radical generator, at 37°C were measured before and after dietary treatment. Plasma β-carotene increased from 0.76 ± 0.16 to 6.45 ± 1.16 µmol/L (P < 0.05) in supplemented but not placebo-treated subjects. The plasma concentrations of other antioxidants did not change significantly in either group. β-Carotene supplementation did not affect basal levels of plasma PC-OOH as measured by HPLC post-column chemiluminescence but did affect AAPH-induced production of PC-OOH. Before supplementation, the induction period of plasma PC-OOH production was 2.4 ± 0.4 h, with levels reaching 5.39 ± 1.50 µmol/L after 6 h of incubation. After supplementation, the induction period increased significantly to 4.2 ± 0.4 h (P < 0.01), with a lower PC-OOH production of 2.16 ± 0.90 µmol/L after 6 h (P < 0.05). In this system, plasma ascorbate concentrations were depleted first, followed by loss of bilirubin and α-tocopherol and then by the sequential loss of γ-tocopherol, urate and β-carotene. These results indicate that β-carotene supplementation increases the plasma antioxidant capacity of older women.