Oral Beta-carotene Research Articles

Clinical and dermoscopic evaluation of red light emitting diodes with beta-carotene versus red light emitting diodes alone in treatment of photoaging

Objectives: Red light-emitting diodes (LEDs) alter the extracellular matrix and increase fibroblast growth factor which increases the number of fibroblasts. Carotenoids have singlet oxygen quenching properties. The objective of this study was to evaluate combined effect of red light with oral beta-carotene in treating photo-damaged skin. Material and Methods: Enrolled subjects were randomized into two groups, A and B. Group A received two sessions/week for 4 weeks of red light therapy and oral beta-carotene 30 mg/day for 12 weeks and Group B received two sessions/week for 4 weeks of red light therapy alone. Before and after clinical as well as dermoscopic photographs were evaluated. Dermoscopic photoaging scale (DPAS), Physician Global Assessment, and Patient Global Assessment was done at baseline, at end of therapy at 4 weeks and at 12 weeks. Results: The mean DPAS of Group A before the treatment was 22.76 which decreased to 10.08 at the end of follow-up period (12 weeks) and was 19.80 in Group B before the treatment which decreased to 10.84. There was 28.25% reduction in DPAS in Group A at 4 weeks whereas it was 16.18% in Group B. Group A showed 56.12% reduction at week 12, while Group B showed 44.78% reduction. There was statistically significant difference in mean percentage reduction in DPAS between the two groups when compared (P = 0.001). Conclusion: Red LED therapy with oral beta-carotene is a better approach for treating photoaging than Red LED therapy alone.

English

Titanium dioxide nanoparticles are one of the famous widely produced nanoparticles in the world that are widely used in paints, cosmetics, plastics, pharmaceutical preparations, water treatment and purification and filtration of air. Beta carotene is provitamin A carotenoid with antioxidant and anti-apoptotic activities. The aim of this study is to evaluate the histopathological changes that occur in the testicular tissue of adult albino rats after intraperitoneal injection of titanium dioxide nanoparticles and to clarify possible protective role of beta carotene against this toxicity. 48 adult male albino rats weighing 180 to 200 g was divided into 4 groups: (I) Control group which consisted of 24 rats divided into 3 equal subgroups (Subgroup Ia (negative control): Received balanced diet for 14 days; Subgroup Ib (positive control): received intraperitoneal injection of distilled water for 14 days; Subgroup Ic: received corn oil by gastric gavage for 21 days (positive control)). Beta carotene group (positive control) which consisted of 8 rats received oral beta carotene 10 mg/kg once daily by gastric gavage for 21 days. The treated group which consisted of 8 rats received intraperitoneal (IP) injection of TiO2 nanoparticles (300 mg/kg) daily for 14 days. The protective group which consisted of 8 rats received 10 mg/kg beta carotene for 7 days by gavage then intraperitoneal (IP) injection of TiO2 nanoparticles (300 mg/kg) for 14 days together with10 mg/kg beta carotene by gavage. Testicular sections were stained with H&E, Masson’s trichrome, vimentin immunohistochemical staining. Serum testosterone level along with quantitative real-time PCR for TNFα gene was measured and statistical analysis was done. Results revealed that marked histopathological changes in testicular tissue was observed in TDN treated group which was improved by co-administration of beta carotene. In addition, statistically significant difference in TNFα expression in testicular tissue, testosterone level, body weights, testes weights and sperm count, motility, tubular dimensions, thickness of capsule in TDN treated group compared to the control group and protective group which showed significant improvement. Thus, titanium dioxide nanoparticles have hazardous effect on testis and that can be improved by beta carotene co-administration. Key words: Adult albino rats, testes, titanium dioxide nanoparticles, β-carotene and gene expression.

Beta-carotene prevents ozone-induced proinflammatory markers in murine skin

Beta-carotene has been thought to protect against oxidative stress generated by ultraviolet radiation and thus prevents skin cancer and skin aging (Biesalski and Obermueller-Jevic, 2001). However, nothing is known about its potential effects against other environmental sources of oxidative stress such as ozone (O3) in skin. Intake of oral beta-carotene supplements before exposure to sunlight (and thus inevitably also to (O3) has been recommended on a population-wide basis. However, although some studies have shown beta-carotene as providing skin protection as an antioxidant, other studies using skin cells in culture have shown that beta-carotene may have unexpected prooxidant properties (Obermüller-Jevic, et al., 2001). Given this, there is an ongoing debate regarding the protective or potentially harmful role(s) of beta-carotene in human skin. In this study, the effect of beta-carotene on ozone's effects on the skin of hairless mice was assessed. After feeding a diet supplemented with 0.5% beta-carotene for 1 month, mice were subjected to O3 exposure (0.8 ppm 6 h/day; 7 days) and the induction of proinflammatory markers such as tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein 2 (MIP2), and inducible nitric oxide synthase (iNOS), and markers of oxidative stress, heme-oxygenase-1 (HO-1), were quantitated. The data showed that beta-carotene downregulated the induction of TNFalpha, MIP2, iNOS, and HO-1 in response to O3. We conclude that beta-carotene provides protection against O3-induced skin oxidative stress in vivo, which is consistent with a protective role for beta-carotene in the skin.

Effects of 6-month daily supplementation with oral beta-carotene in combination or not with benzo[a]pyrene on cell-cycle markers in the lung of ferrets

Epidemiological studies have demonstrated that people who eat more fruits and vegetables (rich in carotenoids) and people who have higher serum beta-carotene (BC) levels have a lower risk of cancer, particularly lung cancer. However, the two main human intervention studies of BC supplementation (the ATBC and the CARET trials) revealed an increased risk of lung cancer among smokers and asbestos workers. Previous studies carried out in the ferret have reported that BC effects are related to dose. Here, we treated ferrets with two concentrations of oral BC (0.8 and 3.2 mg/kg body weight per day) for 6 months, using BC in a formulation also containing dl-alpha-tocopherol and ascorbyl palmitate. The effect of the smoke-derived carcinogenic agent benzo[a]pyrene (BP), with or without low-dose BC, was also analysed. We determined the protein levels and mRNA expression levels of activator protein 1 (c-Jun and c-Fos), c-Myc, cyclin D1, proliferating cellular nuclear antigen and retinoic acid receptor beta. We did not find higher levels of cell proliferation markers in the lung of ferrets treated with BC or signals of squamous metaplasia lesions either. On the other hand, although no evident signals of pulmonary carcinogenesis were observed in animals exposed to BP, BC supplementation in these animals may prevent against excess cell proliferation, since this reestablishes Jun protein and cyclin D1 mRNA levels in the lung of BP-exposed animals. In summary, these results show that the combination of BC with alpha-tocopherol and ascorbyl palmitate does not induce pro-oxidant effects in the lung of ferrets.

Morphology of ferret subcutaneous adipose tissue after 6-month daily supplementation with oral beta-carotene

Adipose tissue is an important retinoid depot and retinoids are known to influence white and brown adipocyte metabolism. Identifying nutrients that can affect the biological activity of the adipose organ would be of great medical interest in the light of the current obesity epidemic and related disorders in developed countries. The vast majority of mammal studies of chronic administration of oral beta-carotene have used murine models, while few have employed mammals exhibiting uptake and processing of intestinal beta-carotene similar to those of humans. While rodents transform practically all ingested beta-carotene into retinol, in ferrets, as in humans, part of the beta-carotene is absorbed and released into the circulation intact. We studied the effects of 6-month daily administration of two doses of oral beta-carotene (0.8 or 3.2 mg/kg/day) on ferret body weight, size of body fat depots, and, using morphological and morphometric methods, on subcutaneous (inguinal) white adipose tissue (WAT). Because of the oral mode of administration, liver, stomach, and small and large intestine were also studied. Control animals received the vehicle. Data show that at the end of treatment the higher dose induced significantly higher body weight compared with controls and significantly higher inguinal fat depot compared with animals treated with the lower dose. In addition, chronic treatment with beta-carotene induced a dose-dependent hypertrophy of white adipocytes and increased neoangiogenesis in subcutaneous WAT in all treated ferrets. Vasculogenesis was independent of adipocyte hypertrophy. We also found focally evident liver steatosis in the ferrets treated with the higher dose of beta-carotene. The other gastrointestinal tract organs studied were not significantly different from those of control animals.

Erythropoetic protoporphyria presenting as “solar urticaria”

Rationale We describe a case of a 6-year old male initially diagnosed with solar urticaria but found to have a genetically based disorder of heme synthesis. Methods The patient presented with a 3-year history of a photosensative dermatosis which occurred during each summer season. He routinely developed pruritic, erythematous, and indurated skin eruptions to the face and arms within minutes of sun exposure. The lesions were not responsive to anti-histamine therapy and would remit within 48 hours. Past medical history was only significant for allergic rhinitis. Family history was significant for a similar rash to sun exposed areas in the mother and allergic rhinitis in the father. Results On exam there was evidence of dermal xerosis, hyperpigmentation and cicatrix formation over the face and hands. No significant lymphadenopathy or hepato-splenomegaly. Laboratory evaluation revealed a mild normochromic normocytic anemia (Hgb=11.2 g/dL), normal ESR and urinalysis, elevated total bilirubin (1.7 mg/dL), and a highly elevated erythrocyte protoporphyrin (>350 ug/dL). An autoimmune screen and 24- hour urine for porphyrin, porphobilinogen and delta-aminolevulinic acid were all negative. Conclusion Erythropoetic Protoporphyria was diagnosed in view of the clinical history and strong laboratory evidence. He had an excellent clinical response to treatment with oral beta-carotene, daily sunscreen, and topical zinc oxide. In summary, this is a young atopic male with porphyria who was originally diagnosed as having sun induced urticaria. As solar urticaria is a rare disorder, especially in children, suspected cases should be carefully assessed to rule out a rheumatologic or metabolic cause for their condition.

Dietary Lutein/Zeaxanthin Decreases Ultraviolet B-Induced Epidermal Hyperproliferation and Acute Inflammation in Hairless Mice

Lutein and zeaxanthin are carotenoids found in green leafy vegetables with interesting antioxidant properties. They are present in high concentrations in the fovea centralis of the human retina and their role in the prevention of age-related macula degeneration has been reported. We have investigated the effect of orally administered lutein and zeaxanthin in the cutaneous response to ultraviolet B irradiation. Female hairless SKh-1 mice receiving 0.4% and 0.04% lutein plus zeaxanthin-enriched diet for 2 wk were exposed to single doses of ultraviolet B radiation. Skin biopsies were taken at 24 and 48 h after irradiation and analyzed for the presence of apoptotic cells, proliferating cells, and expression of proliferating cell nuclear antigen. Our results show a clear ultraviolet-induced dose-dependent inflammatory response. Orally administered 0.4% lutein and zeaxanthin decreased significantly the edematous cutaneous response (p<0.01) as determined by the reduction of the UVB-induced increase of ear bifold thickening. Additionally, dietary carotenoids were efficient in reducing the ultraviolet B-induced increases in the percentage of proliferating cell nuclear antigen (p<0.05), bromodeoxyuridine (p<0.05), and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling-positive cells (p<0.01). These data demonstrate that oral supplementation of lutein and zeaxanthin diminishes the effects of ultraviolet B irradiation by reducing acute inflammatory responses and ultraviolet-induced hyperproliferative rebound.

UV Light, Beta-carotene and Human Skin—Beneficial and Potentially Harmful Effects

Solar radiation is one of the most important environmental stress agents for human skin, causing sunburn, premature skin aging, and skin cancer. Beta-carotene is discussed to protect against photooxidative stress and thus prevent skin damage. Though beta-carotene has been successfully used against photosensitivity in patients with erythropoietic protoporphyria, its beneficial potential in normal skin is still uncertain. A number of experimental studies indicate protective effects of beta-carotene against acute and chronic manifestations of skin photodamage. However, most clinical studies have failed to convincingly demonstrate its beneficial effects so far. Nevertheless, intake of oral beta-carotene supplements before sun exposure has been recommended on a population-wide basis. Recent studies on skin cells in culture have revealed that beta-carotene acts not only as an antioxidant but also has unexpected prooxidant properties. At present, there is an ongoing debate on the protective or potentially harmful role of beta-carotene in human skin.

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.

Variability of the conversion of β-carotene to vitamin A in women measured by using a double-tracer study design

Blood beta-carotene and vitamin A responses to oral beta-carotene are variable in humans. Some individuals are characterized as responders and others as low- or nonresponders. A better understanding of the conditions that produce the variability is important to help design public health programs that ensure vitamin A sufficiency. Our objective was to assess variability in absorption and conversion of beta-carotene to vitamin A in vivo in humans by using a novel double-tracer ¿hexadeuterated (D(6)) beta-carotene and D(6) retinyl acetate approach. Eleven healthy women were housed at the US Department of Agriculture Western Human Nutrition Research Center metabolic unit for 44 d, where they consumed diets adequate in vitamins and minerals except for carotenoids. After an adaptation period, the women were given 30 micromol D(6) retinyl acetate orally, followed 1 wk later with 37 micromol D(6) beta-carotene (approximately equimolar doses). Time-dependent plasma concentration curves were determined for D(6) retinol, D(6) beta-carotene, and trideuterated (D(3)) retinol (derived from D(6) beta-carotene). Mean (+/-SE) absorption of D(6) beta-carotene was 3.3 +/- 1.3% for all subjects. The mean conversion ratio was 0.81 +/- 0.34 mol D(3) retinol to 1 mol D(6) beta-carotene for all subjects. However, only 6 of the 11 subjects had plasma D(6) beta-carotene and D(3) retinol concentrations that we could measure. The mean absorption of D(6) beta-carotene in these 6 subjects was 6.1 +/- 0.02% and their conversion ratio was 1.47 +/- 0.49 mol D(3) retinol to 1 mol D(6) beta-carotene. The remaining 5 subjects were low responders with </=0.01% absorption and a mean conversion ratio of 0.014 +/- 0.004 mol D(3) retinol to 1 mol D(6) beta-carotene. Variable absorption and conversion of beta-carotene to vitamin A both contribute to the variable response to consumption of beta-carotene. Our double-tracer approach is adaptable for identifying efficient converters of carotenoid to retinoid.

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial

The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Piperine, an alkaloid derived from black pepper increases serum response of beta-carotene during 14-days of oral beta-carotene supplementation

The effectiveness of an extract from the fruit of black pepper, consisting of a minimum of 98.0% pure alkaloid piperine, was evaluated for its ability to improve serum response of beta-carotene during oral supplementation using a double-blind, crossover study design. Subjects were randomly selected to ingest a daily beta-carotene dose (15 mg) either with 5 mg of piperine or placebo during each of two 14-day supplementation periods. Inter-subject variability in pre-supplementation serum beta-carotene levels was minimized by limiting the selection of volunteers to healthy, adult males with fasting serum beta-carotene values <20 μg/dL. The results indicate that significantly greater increases (P<0.0001) in serum beta-carotene occurred during supplementation with beta-carotene plus piperine (49.8±9.6μg/dL vs. 30.9±5.4μg/dL) compared to beta-carotene plus placebo. Supplementation with beta-carotene plus piperine for 14-days produced a 60% greater increase in area under the serum beta-carotene curve (AUC) than was observed during supplementation with beta-carotene plus placebo. We suggest that the serum response during oral beta-carotene supplementation is improved through the non-specific, thermogenic property(s) of piperine, described in this paper as thermonutrient in action.

Colposcopic regression patterns in high-grade cervical intraepithelial neoplasia

To evaluate the serial changes in colposcopic and cervicographic findings of women with cervical intraepithelial neoplasia (CIN) II and III enrolled in a phase III randomized comparison of oral beta carotene and placebo. All subjects treated with beta carotene or placebo for at least 6 months were included if they met the criteria of persistent or progressive disease (no change or worsening of CIN grade) or disease regression (improvement of two grades or more). These two groups were compared for changes in colposcopic and cervicographic patterns. Colposcopically directed biopsies and cervicography were done at enrollment and after 6 months. Quarterly Papanicolaou smears and colposcopic assessments also were performed. Findings of mosaic pattern, punctation, and white epithelium were graded and diagrammed at colposcopic examinations. Cervicographic measurements of the centripetal movement of metaplastic epithelium were recorded. Data were analyzed by chi 2 analysis and Fisher exact tests. Data were available for 23 subjects with regression and 16 with persistent lesions. Small lesions were significantly more likely to regress than large ones. Lesions without coarse punctation were significantly more likely to regress than lesions with coarse punctation, and lesions with mild acetowhite changes were more likely to regress than those with dense white epithelium. A pattern of centripetal movement of the metaplastic epithelium toward the cervical os was noted in lesions that regressed, but not in those that persisted or progressed. This study describes the centripetal growth of metaplastic squamous epithelium associated with the regression of CIN II and III. This observation contributes to our understanding of the process of disease regression in CIN and may be useful in identifying individuals for conservative management. Failure to identify this pattern correlates with persistent or progressive disease.

Risk of basal cell and squamous cell skin cancers after ionizing radiation therapy. For The Skin Cancer Prevention Study Group.

Human evidence that ionizing radiation is carcinogenic first came from reports of nonmelanoma skin cancers (NMSCs) on the hands of workers using early radiation devices. An increased risk of NMSC has been observed among uranium miners, radiologists, and individuals treated with x rays in childhood for tinea capitis (ringworm of the scalp) or for thymic enlargement; NMSC is one of the cancers most strongly associated with the atomic bombing of Hiroshima and Nagasaki. Although exposure to ionizing radiation is a known cause of NMSC, it is not yet clear whether therapeutic radiation causes both major histologic types of NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Additionally, the potentially modifying effects, such as latency, age when treated, and type of treatment, are not well understood. We investigated the relative risks of BCC and SCC associated with previous radiation therapy and evaluated these risks in relation to age and time since initial treatment and the medical condition for which radiation therapy was given. The study group comprised individual diagnosed with at least one BCC or SCC from January 1980 through February 1986, who were recruited to participate in a skin cancer prevention trial designed to test whether oral beta-carotene supplementation would reduce the risk of new NMSCs. Patients were identified through the dermatology and pathology records of academic medical centers in Hanover, NH; Los Angeles, CA; San Francisco, CA; and Minneapolis, MN. Each participant completed a questionnaire detailing lifetime residence, pigmentary characteristics, occupational and recreational sun exposure, and history of radiation therapy. At enrollment, a study dermatologist assessed skin type (tendency to burn or tan) and extent of actinic skin damage. Participants were followed with an annual dermatologic examination for an average of 4 years. Of the 5232 potentially eligible individuals, 1805 were enrolled in the trial. We excluded 112 patients who reported previous radiation therapy for skin cancer only and three with missing information on whether they were ever treated with radiation therapy, leaving 1690 patients for the analysis. Approximately 4% of the patients died or discontinued participation for other reasons during each study year. We examined time to occurrence of first new histopathologically confirmed BCC and SCC during the follow-up period in relation to history of radiation therapy (for reasons other than NMSC) using a proportional hazards model. A multiple end points survival model was used to compare the rate ratios (RRs) for BCC and SCC. We also used a longitudinal method of analysis to compute the RR of total new BCC and SCC tumors per person per study year associated with radiation therapy. Using this method, we additionally assessed the potential modifying effects of age at treatment, latency, and type of therapy. All P values were derived from two-sided statistical tests of significance. Among the participants we studied, 597 developed a new BCC (n = 1553 tumors) and 118 developed a new SCC (n = 179 tumors). The time to first new BCC, but not SCC, was associated with prior radiation therapy (RR = 1.7; 95% confidence interval [CI] = 1.4-2.0 and RR = 1.0; 95% CI = 0.6-1.7, respectively; P = .03 for the difference between the RRs). The RR of total BCC tumors was slightly higher (RR = 2.3; 95% CI = 1.7-3.1), but it was still unity for SCC (RR = 1.0; 95% CI = 0.5-1.9). BCC risk appeared to increase with younger age at exposure and time since initially treated, although these effects were only marginally statistically significant (P for trend = .06 and .07, respectively). Also, risk of BCC was more strongly related to treatment for acne (RR = 3.3; 95% CI = 2.1-5.2) than other conditions. Our data suggest that exposure to therapeutic radiation is associated with BCC but not with SCC.

The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or beta-carotene

To investigate the effects of selenium or beta-carotene supplementation in human immunodeficiency virus (HIV)-infected patients, who are known to have deficiencies of selenium and vitamin A, we evaluated the blood enzymatic antioxidant system, including superoxide dismutase (SOD), selenodependent glutathione peroxidase (GPX), and catalase (Cat); glutathione (GSH) status; and plasma selenium concentration. The placebo group consisted of 18 HIV-infected patients with no supplementation, the selenium group was composed of 14 patients receiving oral selenium treatment, and the beta-carotene group comprised 13 patients receiving oral beta-carotene supplementation. All groups were studied for 1 y. At the beginning of the study, a significantly higher SOD activity (P < 0.001) was observed in all HIV-infected patients compared with uninfected control subjects, and GPX activity at baseline was higher in the placebo (P < 0.004) and selenium (P < 0.014) groups than in the control subjects. These higher enzyme activities could be related to an increased synthesis of these enzymes in erythrocyte precursors under oxidative stress. Moreover, we observed significantly lower GSH values in all HIV-infected patients than in control subjects at the beginning of the study (P < 0.001). After selenium or beta-carotene supplementation, no significant difference was observed for SOD activity compared with baseline. On the contrary, GPX activity increased significantly after selenium treatment (P < 0.04 between 3 and 6 mo), whereas a slight increase was found after beta-carotene treatment. Similarly, a significant increase in GSH values was observed at 12 mo compared with baseline both after selenium supplementation (P < 0.001) and beta-carotene supplementation (P < 0.01). Because GPX and GSH play an important role in the natural enzymatic defense system in detoxifying hydrogen peroxide in water, selenium supplementation could be of great interest in protecting cells against oxidative stress. The lower efficiency of beta-carotene could be attributed to the seriousness of the pathology at the time of recruitment into the beta-carotene group.

Neutrophil elastase/alpha 1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation.

Lung inflammation in cystic fibrosis (CF) is associated with an increased release from activated neutrophils of oxidants and proteinases. Free radical generation is not efficiently neutralized, and the major anti-proteinase, alpha 1-proteinase inhibitor (alpha 1-PI) is thought to be oxidatively inactivated. We hypothesized that enhanced antioxidant protection could represent an additional long-term strategy to attentuate the host inflammatory response. The effect on plasma neutrophil elastase/alpha 1-PI (NE/alpha 1-PI) complex levels (as a marker of lung inflammation) and plasma malondialdehyde concentrations (as a marker of lipid peroxidation) of additional oral beta-carotene supplementation was studied in 33 CF patients who had already received long-term vitamin E supplementation. In the presence of a more than 10-fold increase in plasma beta-carotene concentrations (mean +/- SEM) (0.09 +/- 0.01 to 1.07 +/- 0.19 mumol/L; p < 0.0001), a small increase in plasma alpha-tocopherol concentrations (23.8 +/- 1.31 to 28.4 +/- 1.81 mumol/L; p = 0.02), and a more than 50% decrease in plasma malondialdehyde concentrations (1.00 +/- 0.07 to 0.46 +/- 0.03 mumol/L; p < 0.0001), plasma NE/alpha 1-PI complex levels decreased from 102.2 +/- 16.0 to 83.0 +/- 10.4 micrograms/L; (p = 0.02). Plasma retinol concentrations increased (1.05 +/- 0.06 to 1.23 +/- 0.07 mumol/L; p = 0.0001) due to conversion of beta-carotene to retinol, which could have contributed to the decrease in NE/alpha 1-PI complex levels. Based on these results, we speculate that efficient antioxidant supplementation could attenuate lung inflammation in CF.

A randomized clinical trial of beta carotene vs placebo for the treatment of cervical HPV infection

The objective of the study was to determine if oral beta carotene would improve abnormalities observed in Papanicolaou smears or reduce the amount of HPV DNA in genital samples. A randomized double blind placebo controlled trial was designed for 117 women with abnormal cervical morphology, not undergoing laser ablative therapy, at The Royal Women’s Hospital, Victoria. Thirty milligrams of oral beta carotene were administered daily for 12 months. Post-intervention cervical cytology and the amount of HPV DNA present on tampon specimens as determined by polymerase chain reaction and Hybrid Capture were the main outcome measures. After 12 months therapy there was no difference between the beta carotene and placebo groups in Papanicolaou smear results (58% and 62% normal) and HPV positivity (42% and 46% positive) (P> 0.86). Women taking beta carotene were not more likely to have improved cervical cytology or a decrease in the amount of HPV DNA (P> 0.2). The median post-intervention beta carotene level was 0.63 µm ml−1 (range 0.04–1.6) for the beta carotene group and 0.15 µm ml−1 (range 0.02–1.51) for the lecithin group (P < 0.0001). This clinical trial did not identify a beneficial effect of 30 mg of oral beta carotene on cervical cytology, or on the amount of HPV DNA present from tampon specimens.

Mortality Associated With Low Plasma Concentration of Beta Carotene and the Effect of Oral Supplementation

To examine the relationship between beta carotene plasma concentration and beta carotene supplementation and risk of death from major disease causes. Cohort study of plasma concentrations; randomized, controlled clinical trial of supplementation. Medical school-affiliated dermatology practices. A total of 1188 men and 532 women with mean age of 63.2 years, who had enrolled in a randomized clinical trial of beta carotene supplementation to prevent nonmelanoma skin cancer. Oral beta carotene, 50 mg per day for a median of 4.3 years. All-cause mortality and mortality from cardiovascular disease and cancer. During a median follow-up period of 8.2 years, there were 285 deaths. Persons whose initial plasma beta carotene concentrations were in the highest quartile (>0.52 micromol/L [27.7 microg/dL]) had a lower risk of death from all causes (adjusted relative rate [RR], 0.52; 95% confidence interval [CI] 0.44 to 0.87) and from cardiovascular diseases (adjusted RR, 0.57; 95% CI, 0.34 to 0.95) compared with persons with initial concentrations in the lowest quartile (<0.21 micromol/L [11.2 microg/dL]). Patients randomly assigned to beta carotene supplementation showed no reduction in relative mortality rates from all causes (adjusted RR, 1.03; 95% CI, 0.82 to 1.30) or from cardiovascular disease (adjusted RR, 1.16; 95% CI, 0.82 to 1.64). There was no evidence of lower mortality following supplementation among patients with initial beta carotene concentrations below the median for the study group. These analyses provide no support for a strong effect of supplemental beta carotene in reducing mortality from cardiovascular disease or other causes. Although the possibility exists that beta carotene supplementation produces benefits that are too small or too delayed to have been detected in this study, noncausal explanations should be sought for the association between plasma concentrations of beta carotene and diminished risk of death.

Response to oral beta-carotene supplementation in patients with cystic fibrosis: a 16-month follow-up study.

The aim of this study was to determine the efficacy of long-term oral beta-carotene supplementation for correcting impaired beta-carotene status in cystic fibrosis patients. Thirty-five patients (2.3-30.5 years of age) with coefficients of fat absorption of 46-96% (median 88%) received beta-carotene 0.5 mg/kg daily and were followed over a 16-month treatment period. Baseline plasma beta-carotene concentrations in patients (mean +/- SD, 0.09 +/- 0.06 mumol/l) were significantly lower than those of age-matched controls (0.86 +/- 0.56 mumol/l) (p < 0.0001). Concentrations increased rapidly and reached a plateau at or before 3 weeks that was maintained throughout the study period. Values obtained at 3 weeks (0.89 +/- 0.64 mumol/l) were significantly higher (p < 0.0001) than those at baseline and did not differ from controls. Plasma retinol and alpha-tocopherol concentrations increased during the observation period, but remained within normal ranges. Plasma retinyl palmitate, which was below the detection limit in all but one patient at baseline, did not increase. Thus oral beta-carotene supplementation is effective and normalizes beta-carotene status of cystic fibrosis patients without evidence of significant side effects.

Relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids

We evaluated the relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids. In Study 1, beta-carotene intakes were significantly greater in vegetarians than in nonvegetarians. Plasma concentrations of beta-carotene were also significantly higher in vegetarians than in nonvegetarians but only after two nonvegetarians with excessive intake of carrots were omitted. Plasma retinoid (retinol, retinyl esters, and retinoic acid) concentrations were not different between the two groups. In Study 2, female subjects ingested a daily placebo or 90 mg beta-carotene for 3 wk. In the group fed beta-carotene, plasma beta-carotene concentrations were significantly increased from baseline at 1, 2, and 3 wk. No beta-carotene changes were observed in the placebo-fed group. Plasma retinoid concentrations did not change in either group. In Study 3, adipose tissue beta-carotene and retinoid concentrations were measured in men after an oral beta-carotene dose (120 mg, experimental subjects) or no beta-carotene (control subjects). In the experimental subjects, adipose beta-carotene concentrations increased from baseline at 5 and 10 d postdosing. The control group's adipose tissue beta-carotene concentration did not change over a 10-d period. Changes in retinoids in adipose tissue were not significant in either group. In conclusion, dietary and supplemental beta-carotene increased plasma beta-carotene concentrations but had no effect on plasma retinoid concentrations. There may be little tissue metabolism of beta-carotene to retinoids. Therefore, the anticarcinogenic effect of beta-carotene, if any, may be due to properties of the molecule itself.