Beta-carotene Group Research Articles

The Effect of Randomized Beta-Carotene Supplementation on CKD in Men

Beta-carotene (BC) protects the body against free radicals that may damage the kidney and lead to the development of acute kidney injury and chronic kidney disease (CKD). Previous studies in animal models have demonstrated a potential protective effect of 30 mg/kg BC supplementation on renal ischemia or reperfusion injury and subsequently improved kidney function. The extension of these findings to humans, however, remains unclear. Our study leverages previously collected data from the Physicians' Health Study I (PHS I), a large-scale, long-term, randomized trial of middle-aged and older US male physicians testing 50 mg BC every other day for primary prevention of cardiovascular disease and cancer. We examined the impact of randomized BC supplementation on self-reported incident CKD identified by self-reports stating "yes" to kidney disease from annual follow-up questionnaires from randomization in 1982 through the end of the randomized BC intervention at the end of 1995, and on CKD defined as an estimated glomerular filtration rate (eGFR)< 60 ml/min per 1.73 m2 at the end of 1995. Analyses compared incident CKD between BC supplementation and placebo using Cox proportional hazards regression models and logistic regression. We also examined whether smoking status (current vs. former or never smoker) or other factors modified the effect of randomized BC supplementation on CKD. A total of 10,966 participants were randomized to BC, and 10,952 participants were randomized to a placebo group. Baseline characteristics between randomized BC groups were similar. There was no significant benefit between BC supplementation and self-reported incident CKD after adjusting for age and randomized aspirin treatment (hazard ratio [HR]= 0.97, 95% confidence interval [CI]: 0.86-1.08, P-value= 0.56). Stratified by smoking status, there was no significant benefit of BC supplementation and self-reported incident CKD either among former or never smokers (HR= 0.95, 95% CI: 0.84-1.07, P-value= 0.41) or current smokers (HR= 1.08, 95% CI: 0.78-1.50, P-value= 0.64). Smoking status did not modify the association between BC supplementation and incident CKD (P-interaction= 0.47). In subgroup analysis among those with available serum creatinine at the study end (5480 with BC and 5496 with placebo), there was no significant benefit between BC supplementation and CKD based on eGFR< 60 ml/min per 1.73 m2 (odds ratio [OR]= 0.96, 95% CI: 0.85-1.08, P-value= 0.49). Long-term randomized BC supplementation did not affect the risk of incident CKD in middle-aged and older male physicians.

Comparison of effects of curcumin and beta-carotene on ovarian damage caused by cisplatin

Purpose: We aimed the potential protective effects of curcumin (CUR) and beta-carotene (BC) against cisplatin (CIS)-induced ovarian damage using histological and immunohistochemical methods.&#x0D; Materials and Methods: We used 56 female Wistar albino rats, divided randomly into seven groups. Control rats did not receive any treatment; the sham group was administered 1 ml/kg sesame oil by gavage; the CIS group 5 mg/kg CIS; the CUR group 200 mg/kg CUR; the BC group 100 mg/kg BC; the CUR + CIS group, CIS after administration of CUR; the BC + CIS group was pretreated with BC, then administered CIS. The ovaries of all groups were excised five days after the last application. We assessed histopathology and counted and classified follicles. Expression of anti-Mullerian hormone (AMH) and nuclear factor-kappa B (NF-κB) was detected immunohistochemically. Apoptosis was evaluated using the TUNEL method.&#x0D; Results: CUR and BC are protective against decreased numbers of primordial, primary, preantral, secondary, and tertiary follicles caused by CIS. Both Cur and BC reduced ovarian NF-κB levels in comparison to the control group, and AMH immunoreactivity was almost identical for the control and CUR + CIS groups. Apoptotic cell counts indicated that CUR exerts a stronger anti-apoptotic effect than BC.&#x0D; Conclusion: CUR has a protective effect against ovarian damage brought on by CIS and greater antioxidant and anti-inflammatory properties than BC.

​Effect of Beta-carotene Supplementation on Plasma Carotene Content and Fertility of Lactating Crossbred Sahiwal Cows

Background: Beta-carotene (BETA) is a precursor of retinol (Vitamin A) and positively influenced on reproductive efficiency in cows. The aim of the study was to determine the effect of orally supplementation of beta-carotene on plasma carotene content and fertility rate of lactating crossbred Sahiwal cows. Methods: Twenty-four disease-free lactating crossbred Sahiwal cows with a close date of calving were randomly divided into two homogeneous groups for Control group (CONT; n = 12) and Beta-carotene group: 500 mg/cow/d (BETA; n = 12) from 7 days post partum (dpp) until 105 dpp thereafter on concentrations of beta-carotene and selected protein and energy parameters in plasma were determined. In addition, effects on fertility rate were studied. Result: Beta-carotene concentrations increased in plasma of beta-carotene (BETA-group) supplemented cows compared to control (CONT-group) cows (p less than 0.001). In BETA-group cows, urea concentration in blood plasma decreased significantly compared to cows of CONT-group (p less than 0.001) but did not differ in total protein, albumin, glucose and total cholesterol content in cows of both groups. Occurrence of first post partum estrus decreased (p less than 0.001) in beta-carotene (BETA-group: 74 dpp) cows compared to control (CONT-group: 81 dpp) cows. In this study, it was observed that the overall conception rate was higher (p greater than 0.001) in BETA-group: 83.33% (cows pregnant: 10/12) and lesser in the CONT-group: 50.00% (cows pregnant: 6/12). The results of this study indicated that oral supplementation with beta-carotene increased the concentration of beta-carotene and decreased the concentration of urea in plasma and cows with higher blood plasma beta-carotene content improved fertility over cows with lower blood plasma beta-carotene content.

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.

Comparative evaluation of micronuclei in Saudi smokers and non-smokers without any visible oral lesions– A pilot study.

Objectives: A systematic review was conducted to evaluate effectiveness and safety of beta carotenes for the treatment of oral leukoplakia regarding clinical resolution and prevention of malignant transformation. Material and Methods: The systematic search was conducted in three electronic databases and the study’s selection was performed according to pre-set eligibility criteria. Four studies evaluating the efficacy of beta carotenes in oral leukoplakia compared to placebo were included in the review; three of which were assigned for quantitative analysis. Data were extracted, tabulated, quality assessed and statistically analyzed. Results: The meta-analysis revealed that when comparing clinical resolution the beta carotene group favored was favored compared to placebo, with statistically significant difference. However, a meta-analysis comparing beta carotene and placebo groups regarding malignant transformation as a primary outcome failed to show any significant benefit. Furthermore, results showed evidence of beta carotene safety. Conclusion: the overall quality of evidence about efficacy of beta carotene in oral leukoplakia treatment was not high. However, given the obvious safety of this agent, data suggests it could have a promising effect in clinical improvement of oral leukoplakia lesions. However, no evidence supporting its benefits in reducing risk of malignant transformation in these lesions was found. Therefore, further long term, well designed randomized clinical trials are highly recommended.

Efficacy and safety of beta carotones in treatment of oral leukoplakia: systematic review and meta-analysis.

Objectives: A systematic review was conducted to evaluate effectiveness and safety of beta carotenes for the treatment of oral leukoplakia regarding clinical resolution and prevention of malignant transformation. Material and Methods: The systematic search was conducted in three electronic databases and the study’s selection was performed according to pre-set eligibility criteria. Four studies evaluating the efficacy of beta carotenes in oral leukoplakia compared to placebo were included in the review; three of which were assigned for quantitative analysis. Data were extracted, tabulated, quality assessed and statistically analyzed. Results: The meta-analysis revealed that when comparing clinical resolution the beta carotene group favored was favored compared to placebo, with statistically significant difference. However, a meta-analysis comparing beta carotene and placebo groups regarding malignant transformation as a primary outcome failed to show any significant benefit. Furthermore, results showed evidence of beta carotene safety. Conclusion: the overall quality of evidence about efficacy of beta carotene in oral leukoplakia treatment was not high. However, given the obvious safety of this agent, data suggests it could have a promising effect in clinical improvement of oral leukoplakia lesions. However, no evidence supporting its benefits in reducing risk of malignant transformation in these lesions was found. Therefore, further long term, well designed randomized clinical trials are highly recommended.

Raman spectroscopy: A novel experimental approach to evaluating cisplatin induced tissue damage

The aim of this work is to clarify the effect of curcumin and beta-carotene on cisplatin-induced tissue damage and to demonstrate the potential of Raman spectroscopy to detect tissue changes consistent with liver and kidney histopathology as a potential diagnostic adjunct. İn the study, 56 Wistar albino female rats were used and randomly divided into 7 groups (n:8). Sham group received only sesame oil; Cisplatin group, received a single dose injection of cisplatin; Beta-carotene group, treated with beta-carotene orally; Cisplatin + Beta-carotene group, pretreated with beta-carotene 30 min prior to the cisplatin injection, then received cisplatin; Curcumin group, orally treated with curcumin; Cisplatin + Curcumin group, pretreated with curcumin 30min prior to the cisplatin injection, then received cisplatin. The second application was performed 1 week after the first application. One of the liver and kidney tissues was taken to 10% form for histopathological examinations and the others were taken to −80 °C for raman spectroscopy. Received sections were hematoxylin-eosin stained. The avidin-biotin peroxidase method was used for to investigate anti-TNF-α and IL1-β activities. TUNEL method was applied to determine apoptotic cells.According to our histopathological findings, beta-carotene and especially curcumin have been found to possess hepatorenal protective activities. These datas were supported by the microscopic damage scores. Although some of these findings were observed in both the cisplatin + curcumin and cisplatin + beta-carotene groups, the incidence and severity of histopathological lesions were less than the cisplatin group. Both immunohistochemical studies and Raman spectroscopy results consistent with histopathological examination of hematoxylen-eosin stained sections. Raman spectroscopy represents a suitable tool to provide insights into structural factors involved in the mechanisms underlying antitumor effects of platinum drug.

Effect of β-Carotene Supplementation on the Risk of Pneumonia Is Heterogeneous in Males: Effect Modification by Cigarette Smoking.

Beta-carotene has been suggested to be a factor for improving the immune system, which implies that it might decrease the risk of infections. We therefore analyzed whether beta-carotene supplementation influenced pneumonia risk in 14,564 Finnish male smokers of the Alpha-Tocopherol Beta-Carotene (ATBC) Study. There were 231 pneumonia cases in the beta-carotene group and 217 cases in the placebo group. Thus, beta-carotene had no effect on the average incidence of pneumonia, RR=1.07 (95% CI: 0.89-1.29). However, cigarette smoking exposure significantly modified the effect. Beta-carotene increased pneumonia risk by RR=4.0 (95% CI: 1.63-10) among 990 participants who started to smoke at the age of ≥21 y and smoked ≥21 cigarettes per day at the study baseline. However, beta-carotene had no influence on pneumonia risk for the remaining participants. We also analyzed the effect of beta-carotene on participants who quit smoking during the ATBC Study. Among 4,290 participants who quit smoking, the 58 pneumonia cases were evenly distributed between the beta-carotene and placebo groups with RR=0.93 (95% CI: 0.55-1.55). Accordingly, no evidence was found that beta-carotene decreased pneumonia risk; instead, it significantly increased the incidence of pneumonia in a subgroup that covered 7% of the study population.

The key role of targeted betacarotene supplementation on endocrine and reproductive outcomes in goats: Follicular development, ovulation rate and the GH-IGF-1 axis

The possible effects of betacarotene (BC) supplementation on the secretion pattern of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and their possible relationship with total ovarian activity (TOA), was evaluated in adult goats during the breeding season. In October, goats [n=22, 3.5y. old, 7/8 Sannen-Alpine] were randomly assigned to: a) Betacarotene group [BC, n=10; 45.9±1.97kg live weight (LW), 3.04±0.08 units, body condition score (BCS), supplemented with 50mg of BC goat day−1], and b) Control group [CONT, n=12; 46.2±2.04kg LW, 3.0±0.08 units, BCS]. An ultrasonographic scan was performed to evaluate corpus luteum number (OR) and antral follicle number (AF); TOA=OR+AF. Average LW and BCS did not differ (p>0.05) during the experimental period, yet BC-goats reflected an increased OR (3.4±0.2 vs. 2.8±0.2), AF (5.0±0.6 vs. 3.4±0.6) and TOA (8.4±0.5 vs. 6.2±0.6). Regarding the endocrine profile, the lowest (p<0.05) serum GH average concentrations (10.0 vs. 14.3±1.0ngmL−1; p=0.01) and GH-AUC (3670.4 vs. 5235.7±369.8 units; p=0.01), were observed in the BC-supplemented group. Neither serum IGF-1 concentrations (254.6±28.9ngmL−1 p>0.05) nor GH-PULSE (1.4±0.5 pulses 6h−1 p>0.05) differed between treatments. We document a potential role of BC as modulator of somatotrophic function, decreasing mean serum concentration and the area under the curve of GH, while also noting a positive action upon ovarian function with increases in ovulation rate and antral follicular development; such outcomes may embrace not only physiologic significance but also potential translational applications.

Beta-carotene supplementation positively affects selected blood metabolites across time around the onset of puberty in goats

The possible effect of beta-carotene supplementation upon peripubertal changes in serum concentrations across time for total protein (TP), urea (UR), cholesterol (CHOL), and glucose (GLU) around puberty onset was evaluated. The experiment was carried out from June to November and prepubertal goats (n = 17, 3 months old, 7/8 Saanen-Alpine, 1/8 Criollo) were randomly assigned to: (1) beta-carotene group (BC) (n = 9; 17.3 ± 1.0 kg live weight (LW), 3.3 ± 0.12 body condition score (BCS), oral supplementation with 50 mg beta-carotene per day per goat) and (2) control group (CC) (n = 8; 16.1 ± 1.0 kg LW, 3.1 ± 0.12 BCS). Serum blood samples were collected along the experiment to quantify progesterone concentrations (P4) through radioimmunoassay, while TP, UR, CHOL, and GLU through spectrophotometric analyses. No differences (P &amp;gt; 0.05) occurred between treatments regarding LW and BCS, and TP (67.6 ± 2.4 g/l), UR (3.8 ± 0.17 mmol/l), GLU (5.06 ± 0.09 mmol/l), and CHOL (1.62 ± 0.07 mmol/l) concentrations. However, while a treatment × time interaction occurred between treatments for TP, GLU, CHOL (P &amp;lt; 0.05) favouring the BC group, an increased serum UR levels occurred in the CC group. Nonetheless, such general serum metabolite profile was related neither to the age (215.7 vs 226.5 ± 6.6 days; P &amp;gt; 0.5) nor to the percentage (44.4 vs 25.0 ± 17.0%; P &amp;gt; 0.05) of goats reaching puberty in the BC and CC groups, respectively. Results should help speed-up goat productivity while may also engender key management applications to different animal industries.

Effect of beta-carotene on titanium oxide nanoparticles-induced testicular toxicity in mice

This study evaluated the protective effect of beta-carotene (BC) on titanium oxide nanoparticle (TNP) induced spermatogenesis defects in mice. Thirty-two NMRI mice were randomly divided into four groups. BC group received 10mg/kg of BC for 35days. TNP group received 300mg/kg TNP for 35days. TNP+BC group initially received 10mg/kg BC for 10days and was followed by concomitant administration of 300mg/kg TNP for 35days. Control group received only normal saline for 35days. Epididymal sperm parameters, testicular histopathology, spermatogenesis assessments and testosterone assay were performed for evaluation of the TNP and BC effects on testis. Serum testosterone levels were markedly decreased in TNP-intoxicated mice. Epididymal sperm parameters including sperm number, motility and percentage of abnormality were significantly changed in TNP-intoxicated mice (p < 0.01). Histopathological criteria such as epithelial vacuolization, sloughing of germ cells and detachment were significantly increased in TNP-intoxicated mice (p < 0.001). BC+TNP treatment significantly prevented these changes (p < 0.05). BC also significantly elevates testosterone levels in BC+TNP group compared to TNP-treated mice (p < 0.01). The results of this study demonstrated that BC improved the spermatogenesis defects in TNP-treated mice. BC had a potent protective effect against the testicular toxicity and might be clinically useful.

Long-term betacarotene supplementation positively affects serum triiodothyronine concentrations around puberty onset in female goats

The effect of betacarotene (BC) supplementation on serum triiodothyronine (T3) levels over time in prepubertal goats was evaluated. Goats (n=17; 3 months old; 7/8 Saanen-Alpine; 26° NL) were randomly assigned to one of the following two groups: 1) the betacarotene group, supplemented daily with 50mg of BC (n=9; live weight [LW]: 17.3±1.0kg; body condition score [BCS]: 3.34±0.12), or 2) the control group (CC; n=8; LW: 16.1±1.0kg; BCS=3.17±0.12). The initial mean LW (16.7±1.0kg) and BCS (3.31±0.12) were similar (p>0.05) in both groups. Whereas BC supplementation did not affect the onset of puberty (215.7 vs. 226.7±6.6 days; p>0.05) for the BC and CC, respectively, increases in serum T3 during the second half of the experiment were observed in the BC supplementation group (p<0.05). As the LW and serum T3 levels increased, the natural photoperiod decreased, revealing a negative correlation (p<0.05) between the variables; the observed values were r=−0.94 for LW and photoperiod and r=−0.41 for T3 and photoperiod. Long-term BC supplementation was not associated with a precocious onset or an increased percentage of goats reaching puberty. Long-term BC supplementation positively affected the release pattern of triiodothyronine over time, suggesting a potential role of BC as a thyroid-activating molecule; these results might possess clinical significance.

Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration

Oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been shown to reduce the risk of progression to advanced age-related macular degeneration (AMD). Observational data suggest that increased dietary intake of lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]), or both might further reduce this risk.To determine whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation decreases the risk of developing advanced AMD and to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation.The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, randomized, double-masked, placebo-controlled phase 3 study with a 2 × 2 factorial design, conducted in 2006-2012 and enrolling 4203 participants aged 50 to 85 years at risk for progression to advanced AMD with bilateral large drusen or large drusen in 1 eye and advanced AMD in the fellow eye.Participants were randomized to receive lutein (10 mg) + zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA + EPA, or placebo. All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both.Development of advanced AMD. The unit of analyses used was by eye.Median follow-up was 5 years, with 1940 study eyes (1608 participants) progressing to advanced AMD. Kaplan-Meier probabilities of progression to advanced AMD by 5 years were 31% (493 eyes [406 participants]) for placebo, 29% (468 eyes [399 participants]) for lutein + zeaxanthin, 31% (507 eyes [416 participants]) for DHA + EPA, and 30% (472 eyes [387 participants]) for lutein + zeaxanthin and DHA + EPA. Comparison with placebo in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD (hazard ratio [HR], 0.90 [98.7% CI, 0.76-1.07]; P = .12 for lutein + zeaxanthin; 0.97 [98.7% CI, 0.82-1.16]; P = .70 for DHA + EPA; 0.89 [98.7% CI, 0.75-1.06]; P = .10 for lutein + zeaxanthin and DHA + EPA). There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. More lung cancers were noted in the beta carotene vs no beta carotene group (23 [2.0%] vs 11 [0.9%], nominal P = .04), mostly in former smokers.Addition of lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation in primary analyses did not further reduce risk of progression to advanced AMD. However, because of potential increased incidence of lung cancer in former smokers, lutein + zeaxanthin could be an appropriate carotenoid substitute in the AREDS formulation.clinicaltrials.gov Identifier: NCT00345176.

Betacarotene supplementation increases ovulation rate without an increment in LH secretion in cyclic goats

This study aimed to evaluate the effects of betacarotene (BC) supplementation on ovulation rate (OR) and luteinizing hormone (LH) secretion in adult goats during the breeding season. Additionally, total ovarian activity (TOA) comprising the total number of ultrasonographically detectable antral follicles (AF) and corpora lutea (OR) was also assessed. In early October, adult goats [n=22, 3.5 years of age, 7/8 Sannen-Alpine; 26°N, 103°W at 1117m.a.s.l.] were randomly assigned to: (i) BC group (BCG), orally supplemented with 50mg of BC/goat/day [n=10; live weight (LW)=45.9±2.0kg, body condition score (BCS; range: 0-emaciated to 5-obese)=3.0±0.1], and (ii) control group (CONT) [n=12; LW=46.2±2.0kg, BCS=3.0±0.1]. All animals received a basal diet of alfalfa hay, corn silage and corn grain, with free access to water and mineral salts. The whole experimental period spanned 34 days before and 17 days after ovulation. On day 23 of the experiment, estrus was synchronized with progestin-releasing intravaginal sponges; 36h prior to estrus, an intensive blood sampling (every 15min for 6h) was performed to determine mean LH concentrations, pulsatility (LH-PULSE) and area under the curve (LH-AUC) for serial LH concentrations. Afterwards, by the end of the luteal phase (i.e., 17 days after the onset of estrus), an ultrasonographic scanning was performed to evaluate OR and TOA [AF+OR]. The average LW and BCS did not differ (p>0.05) during the experimental period. BC-supplemented goats showed an increase in OR (3.4±0.2 versus 2.8±0.2; p<0.05) and exhibited lower (p<0.05) serum LH concentrations, LH-AUC and LH-PULSE compared to CONT. A positive correlation was recorded between OR and LW (r2=0.42, p<0.05) and BCS (r2=0.47, p<0.05). In addition, AF (5.0±0.6 versus 3.4±0.6) and TOA (8.4±0.6 versus 6.2±0.6) were greater (p<0.05) in the BC-supplemented group than CONT. Supplementation with BC enhanced ovarian follicular development and ovulation rate in adult female goats under decreased photoperiods through LHRH-independant pathways or direct effects of BC on ovarian function.

Effect of Beta-Carotene on Oxidative Stress and Expression of Cardiac Connexin 43

BackgroundIntervention studies have shown an increased mortality in patients who received beta-carotene. However, the mechanisms involved in this phenomenon are still unknown. ObjectiveEvaluate the influence of beta-carotene on oxidative stress and the expression of connexin 43 in rat hearts. MethodsWistar rats, weighing approximately 100 g, were allocated in two groups: Control Group (n = 30), that received the diet routinely used in our laboratory, and Beta-Carotene Group (n = 28), which received beta-carotene (in crystal form, added and mixed to the diet) at a dose of 500 mg of beta carotene/kg of diet. The animals received the treatment until they reached 200-250g, when they were sacrificed. Samples of blood, liver and heart were collected to perform Western blotting and immunohistochemistry for connexin 43; morphometric studies, dosages of beta carotene by high performance liquid chromatography as well as reduced glutathione, oxidized glutathione and lipids hydroperoxides were performed by biochemical analysis. ResultsBeta-carotene was detected only in the liver of Beta-Carotene Group animals (288 ± 94.7 μg/kg). Levels of reduced/ oxidized glutathione were higher in the liver and heart of Beta-Carotene Group animals (liver - Control Group: 42.60 ± 1.62; liver - Beta-Carotene Group: 57.40 ± 5.90; p = 0.04; heart: - Control Group: 117.40 ± 1.01; heart - Beta-Carotene Group: 121.81 ± 1.32 nmol/mg protein; p = 0.03). The content of total connexin 43 was larger in Beta-Carotene Group. ConclusionBeta-carotene demonstrated a positive effect, characterized by the increase of intercellular communication and improvement of anti-oxidizing defense system. In this model, mechanism does not explain the increased mortality rate observed with the beta-carotene supplementation in clinical studies.

Short-term beta-carotene-supplementation positively affects ovarian activity and serum insulin concentrations in a goat model.

In early October 2010, adult goats (no.=22, 3.5 yr old, 7/8 Sannen-Alpine, 26° N, 103° W, at 1117 m), were randomly assigned to: i) beta-carotene group (BC) [no.=10; live weight (LW)=45.9±1.97 kg, body condition score (BCS) =3.04±0.08; orally supplemented with 50 mg of BC per goat per day]; ii) control group (CONT) (no.=12; LW=46.2±2.04 kg, BCS=3.0±0.08). Animals received a basal diet of alfalfa hay, corn silage, and corn grain, having free access to water, shade, and mineral salts. During the second half of October, estrus was synchronized by using intravaginal sponges. Thereafter, by mid-follicular phase, an intensive blood sampling (6 h × 60 min) was performed to evaluate serum insulin concentrations (INS) by radioimmunoassay. By the end of the luteal phase, an ultrasonographic scanning was performed to evaluate total ovarian activity (TOA) [TOA=total follicles (TF) + total corpus luteum (TCL)]. The whole experimental period consisted of 34 days pre- and 17 days post-ovulation, for a total of 52 days. Average LW and BCS did not differ (p>0.05) during the experimental period. Nonetheless, increases in TF no. (5.0 vs 3.4±0.6 units; p=0.05), TCL no. (3.4 vs 2.8±0.2 units; p=0.05), TOA (8.1 vs 6.2±0.6 units; p=0.05) and INS (4.6 vs 3.9±0.4 ng ml-1; p=0.05) favored to the BC-supplemented group. A positive correlation between LW (r(2)=0.42; p=0.04) and BCS (r(2)=0.47; p=0.02) with respect to ovulation rate, was detected. BC-supplementation increased ovarian activity in the female goat while positively affected the release pattern of insulin, suggesting a potential role of BC as a central and/or pancreas-activating molecule in adult goats; such results may hold not only physiologic but also clinical significance.

Beta-carotene Antioxidant Use During Radiation Therapy and Prostate Cancer Outcome in the Physicians' Health Study

The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined as prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group. The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.

Long-term betacarotene-supplementation enhances serum insulin concentrations without effect on the onset of puberty in the female goat

The effect of betacarotene (BC) supplementation on the onset of puberty and serum insulin levels in goats was evaluated in the study. In June, prepuberal goats (n=17; 3 months old; 7/8 Saanen-Alpine; 26° NL) were randomly assigned to one of two groups: 1/ betacarotene group supplemented daily with 50 mg of BC (n=9; live weight [LW]: 17.3±1.0 kg; body condition score [BCS]: 3.34±0.12) or 2/ control group (CONT; n=8; LW:16.1±1.0 kg; BCS=3.17±0.12). From June to November, an intermittent blood sampling was performed twice per week in both groups to evaluate serum progesterone (P(4)), while monthly samples were intended for insulin (INS) determination. Initial mean LW (16.7±1.0 kg) and BCS (3.31±0.12) were similar (p>0.05) in both groups. Mean serum insulin (1.37 vs. 1.18±0.09 ng/ml), age of puberty (215.7 vs. 226.5±6.6 days) and the percentage of goats reaching puberty (44.4 vs. 25.0±17.0%) did not differ (p>0.05) between BC and CONT group, respectively. However, increase in serum insulin during the second half of the experiment was observed in BC group (p<0.05) which was positively correlated with LW (r=0.95; p<0.05). In addition, as LW (r=-0.89) and serum insulin (r=-0.76) levels increased, the natural photoperiod decreased, revealing negative correlations (p<0.05) between the respective variables. In this study, BC supplementation did not promote precocious puberty and did not affect the percentage of goats reaching activation of the hypothalamic-hypophyseal-gonadal axis during the establishment of puberty. Nonetheless, BC supplementation positively affected the release pattern of insulin suggesting a potential role of BC as pancreas-activating molecule.

Effects of Vitamin A or Beta Carotene Supplementation on Pregnancy-Related Mortality and Infant Mortality in Rural Bangladesh

Maternal vitamin A deficiency is a public health concern in the developing world. Its prevention may improve maternal and infant survival. To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality. Cluster randomized, double-masked, placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks (84 days) postpartum in rural northern Bangladesh between 2001 and 2007. Interventions Five hundred ninety-six community clusters (study sectors) were randomized for pregnant women to receive weekly, from the first trimester through 12 weeks postpartum, 7000 μg of retinol equivalents as retinyl palmitate, 42 mg of all-trans beta carotene, or placebo. Married women (n = 125,257) underwent 5-week surveillance for pregnancy, ascertained by a history of amenorrhea and confirmed by urine test. Blood samples were obtained from participants in 32 sectors (5%) for biochemical studies. All-cause mortality of women related to pregnancy, stillbirth, and infant mortality to 12 weeks (84 days) following pregnancy outcome. Groups were comparable across risk factors. For the mortality outcomes, neither of the supplement group outcomes was significantly different from the placebo group outcomes. The numbers of deaths and all-cause, pregnancy-related mortality rates (per 100,000 pregnancies) were 41 and 206 (95% confidence interval [CI], 140-273) in the placebo group, 47 and 237 (95% CI, 166-309) in the vitamin A group, and 50 and 250 (95% CI, 177-323) in the beta carotene group. Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 (95% CI, 0.75-1.76) and 1.21 (95% CI, 0.81-1.81), respectively. In the placebo, vitamin A, and beta carotene groups the rates of stillbirth and infant mortality were 47.9 (95% CI, 44.3-51.5), 45.6 (95% CI, 42.1-49.2), and 51.8 (95% CI, 48.0-55.6) per 1000 births and 68.1 (95% CI, 63.7-72.5), 65.0 (95% CI, 60.7-69.4), and 69.8 (95% CI, 65.4-72.3) per 1000 live births, respectively. Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study (1.46 [95% CI, 1.42-1.50] μmol/L vs 1.13 [95% CI, 1.09-1.17] μmol/L and 1.18 [95% CI, 1.14-1.22] μmol/L, respectively; P < .001) and reduced, but did not eliminate, gestational night blindness (7.1% for vitamin A vs 9.2% for placebo and 8.9% for beta carotene [P < .001 for both]). Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh, compared with placebo, did not reduce all-cause maternal, fetal, or infant mortality. clinicaltrials.gov Identifier: NCT00198822.

β‐Carotene exhibits antioxidant and anti‐apoptotic properties to prevent ethanol‐induced cytotoxicity in isolated rat hepatocytes

The study was designed to evaluate the effects of 1 microM beta-carotene on antioxidant status in ethanol-treated rat hepatocytes and investigate possible anti-apoptotic mechanisms of beta-carotene in protecting ethanol-induced cytotoxicity. The isolated rat hepatocytes were incubated for 48 h in a medium with or without alcohol (100 mM) and mu-carotene (1 microM) using the following groups: the control (C), beta-carotene (CB), ethanol (E), and ethanol + beta-carotene (EB) groups. The cell viability, antioxidative status, cytochrome P450 2E1 (CYP2E1) and caspase expressions in hepatocytes were measured. The E group demonstrated lower cell viability, glutathione (GSH) levels, and lipid peroxide accumulation in rat hepatocytes; meanwhile, CYP2E1, caspase-3, and caspase-9 expressions increased. In contrast, cell viability, GSH levels, and glutathione reductase (GRD) activity significantly increased while lipid peroxides and expressions of CYP2E1, casapse-3, and caspase-9 decreased in the EB group. The results suggest that ethanol treatment decreases cell viability in rat hepatocytes via induced oxidative stress. 1 muM beta-carotene decreased oxidative stress and prevented ethanol-induced cell death by inhibiting caspase-9 and caspase-3 expression.