Doses Of Beta-carotene Research Articles

Interactions of Oral β-Carotene and Canthaxanthin in Ferrets

Interactive effects of an oral dose of equal quantities of beta-carotene and either canthaxanthin or lycopene on serum and tissue beta-carotene accumulations were investigated in domestic ferrets. Like humans, ferrets absorb a substantial portion of ingested beta-carotene intact and accumulate it in tissues. After the ferrets ingested a low carotenoid purified diet for 13 d, they were randomly assigned to one of two groups of six animals. One group was dosed with beta-carotene (10 mg/kg body weight) and the other with beta-carotene and either canthaxanthin (Experiment 1) or lycopene (Experiment 2) (10 mg/kg body weight for each). In Experiment 1, ferrets that received a combined dose of beta-carotene and canthaxanthin had serum beta-carotene concentrations that were significantly lower at 8, 12 and 24 h post-dosing (P < 0.05), compared with those that received an individual dose of beta-carotene; liver, adrenal and kidney beta-carotene concentrations were also significantly reduced. In Experiment 2, ferrets that received a combined dose of lycopene and beta-carotene had lower serum and tissue beta-carotene concentrations than in those that received beta-carotene alone; the differences were not statistically significant with the exception of serum beta-carotene concentrations at 24 h post-dosing. The results suggest that, at the doses given, a concurrent oral canthaxanthin dose has a specific antagonistic effect on the bioavailability of a beta-carotene dose in ferrets.

Phytoene Is More Efficiently Absorbed Than Lycopene by In Vitro Intestinal Cells but Is Absorbed and Cleared Similarly to Lycopene by In Vitro Prostate Cancer Cells

ObjectivesConsuming tomatoes and the tomato carotenoid lycopene (LYC) is epidemiologically associated with reduced prostate cancer risk. Tomato carotenoids, including LYC, phytoene (PE), and beta-carotene (BC), are found in human prostate tissue, with greater PE: LYC ratios found in the blood and prostate tissue relative to the diet. We tested the hypothesis that PE is more efficiently absorbed by prostate cells and by absorptive intestinal cells than LYC, explaining the enrichment of PE in blood and prostate tissue. MethodsIn vitro prostate cancer (LNCaP, PC-3) and non-cancerous prostate epithelial (RWPE-1) cells were treated with human serum enriched with PE, LYC, BC, or control (final media concentration 1 uM) for 6 hours. Clearance of PE, LYC, and BC from LNCaP cells was monitored for 48 hours after a 16 hour pre-incubation with carotenoids (n = 5 trials). Differentiated in vitroabsorptive intestinal cells (Caco-2 HTB-37 cultured 21 d on a permeable support) were treated with mixed lipid micelles and either PE, LYC, BC, or no carotenoid (final media carotenoid concentration 2 uM) for 4 or 24 h (n = 5 trials). Cell and media carotenoid concentrations were measured by HPLC-PDA. ResultsPC-3s absorbed 3.8%, 1.9%, and 2.5% (not significantly different, ns) and LNCaP cells absorbed 1.5%, 2.6%, and 2.0% of the LYC, PE, and BC (ns) doses, respectively, while RWPE-1 cells absorbed more of the BC dose (8.7%) than the PE dose (0.4%, P < 0.05), and LYC dose absorption was intermediate and similar to both PE and BC (2.5%). LNCaP cells cleared PE at the same rate as BC and LYC over 48 h. Intestinal Caco-2 cells absorbed more PE dose at 4 and 24 h (16.3%, 10.8%) than LYC (0.6%, 0.9%, respectively) or BC (5.8%, 7.5% respectively) (P < 0.05), while the amount of carotenoid recovered in the basolateral media showed a similar, though non-significantly different, pattern. ConclusionsThese results align with whole body pharmacokinetic findings suggesting that differences in intestinal absorption may be a key determinant in relative tissue carotenoid accumulation, and reveal that cancer versus non-cancer cell types may differ in carotenoid absorption characteristics. Funding SourcesNIH NCCIH/ODS R01 AT008576.

Beta-Carotene Affects the Effects of Heme Oxygenase-1 in Isolated, Ischemic/Reperfused Rat Hearts: Potential Role of the Iron.

Beta-carotene (BC) is a well-known antioxidant. However, increasing evidence shows that under severe oxidative conditions, BC can become pro-oxidant, an effect that may be enhanced in the presence of iron (II). In our earlier studies, we observed that despite increasing heme oxygenase-1 (HO-1) levels in the heart, the protective effects of BC have been lost when it was used at a high concentration. Since iron releases from heme as a consequence of HO-1 activity, we hypothesized that the application of an iron-chelator (IC) would reverse the lost cardiac protection associated with an elevated HO-1 level. Thus, in the present study, we investigated the effects of desferrioxiamine (DFO) in isolated, ischemic/reperfused rat hearts after long-term treatment with vehicle or high-dose (HD) BC. Vehicle or 150 mg/bw kg daily doses of BC were administered to the rats for 4 weeks, and then their hearts were removed and subjected to 30 min of global ischemia (ISA) followed by 120 min of reperfusion (REP). During the experiments, cardiac function was registered, and at the end of the REP period, infarct size (IS) and HO-1 expression were measured. The results show that DFO treatment alone during REP significantly ameliorated postischemic cardiac function and decreased IS, although HO-1 expression was not increased significantly. In hearts isolated from BC-treated rats, no cardioprotective effects, despite an elevated HO-1 level, were observed, while DFO administration after ISA resulted in a mild improvement in heart function and IS. Our results suggest that iron could have a role whether BC exerts antioxidant or pro-oxidant effects in ISA/REP-injured hearts.

Kinetics of hydrolysis reactions and triacylglycerols oxidation in olive oil during prolonged storage

The article presents the results of studies on the effect of the antioxidant beta-carotene and storage temperature on hydrolytic and oxidative processes occurring during storage of extra virgin olive oil obtained from olives grown in the soil and climatic conditions in Syria. The research aims to study the effect of temperature and beta-carotene on the kinetics of the hydrolysis reactions of triglycerides and fatty acids oxidation in olive oil during storage. The object of the study was extra virgin olive oil obtained from olives grown in Syria according to the generally accepted technology in 2019. And beta-carotene, produced by Ekoresurs, has been used as a natural antioxidant. The kinetics of the hydrolysis and oxidation reaction was evaluated by studying the change in the content of saturated and unsaturated fatty acids during storage of the control sample from olive oil (sample No. 1), and experimental samples with the addition of beta-carotene at concentrations of 400 mg/L (sample No. 2) and 600 mg/L (sample No. 3). These samples were stored at 18 ° C. And sample No. 4 was stored without adding beta-carotene at 4 ° C. Upon receipt for storage and during this process, the content of saturated and unsaturated fatty acids in the test samples was determined periodically by gas chromatography on an LC-20 Shimadzu chromatograph, and organoleptic quality indicators were evaluated on a five-point scale. In addition, the content of triacylglycerols, saturated and unsaturated fatty acids were determined based on the change in beta-carotene dose, temperature, and period of storage. Also, the rate constants of the fatty acid oxidation reaction have been calculated. It was shown that the minimum rate of free fatty acids oxidation during storage of extra virgin olive oil for 7 months was in the olive oil sample stored at + 18 ° C with the addition of 400 mg/L of beta-carotene, as well as in the olive oil sample stored in the refrigerator at + 4 ° C without adding antioxidant.

Influence of temperature and beta-carotene on the processes of hydrolysis and oxidation of triacylglycerins in extra virgin olive oil during storage

The article presents the results of studies on the effect of antioxidant beta-carotene and storage temperature on hydrolytic and oxidative processes occurring during storage of extra virgin olive oil obtained from olives grown in the soil and climatic conditions of Syria. The aim is to study the effect of temperature and beta-carotene on the kinetics of reactions of hydrolysis of triacylglycerides (TAG) and oxidation of free fatty acids (FFA) of olive oil during storage. The object of the study was extra virgin olive oil obtained from olives grown in the soil and climatic conditions of Syria according to the generally accepted technology (harvest 2019). Control sample № 1 (without the addition of antioxidant) and experimental samples with the addition of beta-carotene in the amount of 400 (№ 2) and 600 mg/100 g (№ 3) were stored at a temperature of 18 °C for 7 months. Oil sample № 4 without the addition of antioxidants was stored at 4 °C. In the samples under study, the acid value was periodically determined by the titration method, according to the change in which the formation of free fatty acids during the hydrolysis of TAG, as well as the peroxide value characterizing the formation of FFA oxidation products, was estimated. The organoleptic assessment of the oil quality indicators according to the studied descriptors was 5 points. The rate constants of TAG hydrolysis and oxidation of FFA in olive oil have been calculated. It has been shown that during the storage of experimental oil samples the hydrolytic and oxidative processes of TAG significantly slow down with the addition of the antioxidant beta-carotene. It was found that minimal changes in the content of TAG hydrolysis products and FFA oxidation during storage of olive oil at a temperature of + 18 °C are characteristic for samples containing 400 mg/L of beta-carotene and for oil samples stored at a temperature of + 4 °C without the addition of an antioxidant. Expiration dates of olive oil are substantiated depending on the dose of beta-carotene and storage temperature

The comparison of pegylated liposomal doxorubicin and beta-carotene effects on JAR and JEG-3 choriocarcinoma human cell culture models

Objective:The aim was to investigate the effectiveness of pegylated liposomal doxorubicin (PLD), beta-carotene, and a combination of PLD and beta-carotene on JAR and JEG-3 human choriocarcinoma (CC) cell lines for the treatment of CC.Material and Methods:JAR and JEG-3 cells were cultured. PLD and beta-carotene trial groups were determined with different doses (for single drug trial; PLD 1, 2, 5 μg/mL and beta-carotene 1, 5, 10 μg/mL, and for combined drug trial; all PLD doses combined with beta-carotene 5 μg/mL). Drugs were administered to cultures simultaneously, and 72 hours later the cells were detached using trypsin-ethylenediamine tetraacetic acid solution. The percentage of apoptotic cells was determined by flow cytometry after annexin V staining. One set of the supernatant was collected before trypsin application to investigate beta-human chorionic gonadotropin (β-hCG) and hyperglycosylated hCG (H-hCG) levels. Statistical analyses of the apoptotic ratios were performed using Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney U tests.Results:Apoptosis increased in JAR and JEG-3 cultures after treatment with all doses of PLD (p<0.05). A single application of each beta-carotene dose increased apoptosis in JAR cells (p<0.05) but had no apoptotic effects on JEG-3 cells. In the PLD and beta-carotene combination group, apoptosis increased in both JAR and JEG-3 cells (p<0.05).Conclusion:To our knowledge, this is the first investigation of the effectiveness of PLD, beta-carotene, and PLD + beta-carotene combination therapy in two different CC cell lines. PLD is a promising chemotherapeutic drug, and beta-carotene can be used as a novel non-chemotherapeutic agent for treatment of CC. Based on the results of this study, vitamin A supplementation may have promise as a preventive measure. However, these data need support from animal experiments and clinical trials.

Evaluation of novel and superior formulation CaroTexTM developed by Biofusion Technology

Per WHO, vitamin A deficiency is a systemic disease affecting cells, organs throughout the body. The gradual depletion of vitamin A stores results in xerophthalmia, night blindness, xerosis etc., reversed by vitamin A therapy. Beta-Carotene, a carotenoid, is the precursor of vitamin A, which cannot be synthesized by the human body. Hence beta carotene formulation has gathered considerable attention in the healthcare industry. Hydrophobicity of Beta carotene being a major challenge in the formulation, Zeushygia Life Sciences Pvt. Ltd (Telangana India) developed a novel beta carotene formulation, CaroTex, with enhanced bioavailability. The present study assesses the bioavailability of CaroTex in a rodent model. The animals were divided into 5 groups, Normal Control, Vehicle Control, Standard beta Carotene, Comparator and CaroTex. As rats efficiently convert beta carotene into vitamin A, high dose of beta-carotene (50mg/kg) was given orally for 7 consecutive days. Beta carotene, its metabolic product retinal were measured in rat liver. It was observed that beta carotene concentration in rats fed with CaroTex was about 1.70, 2.55 times higher than Comparator and control respectively whereas the concentration of retinal was the same in all groups. It is evident from this study that novel formulation technology (BioFusion Technology) of CaroTex reflects in relatively higher concentration levels of beta carotene.

Water buffalo bull fertility selection by sperm nuclear shape: Model development and evaluation

Dietary carotenoids have a high antioxidant capacity, so it has been hypothesised that carotenoid supplimentation will improve sperm production and quality by protecting sperm from oxidative damage. The effects of carotenoids on sperm have only been assessed in three vertebrate species, and evidence for improved sperm concentration and motility remains equivocal. One reason for this might be that in most studies there has not been an assessment of the effects of single carotenoid compounds over a range of doses. Applied research focused on developing ways to improve sperm quality could benefit the captive breeding and conservation of threatened species. The aim of the present study was to assess a dose-dependent effect of beta-carotene supplementation on sperm concentration and motility in the endangered booroolong frog (Litoria booroolongensis). Individuals were supplemented with one of four beta-carotene doses (0, 0.1, 1 and 10 mg/g) from hatching until sexual maturity (53 weeks). Sperm concentration was determined prior to activation, and percent sperm motility and sperm velocity were measured at 0, 3 and 6 h post-activation using computer-assisted sperm analysis. Unexpectedly, beta-carotene had no significant effect on sperm concentration, percent motility or velocity at any time point, providing no evidence for beneficial effects. Findings of the present study indicate there are likely to be species-specific differences in sperm production and motility that influence the risk of oxidative damage to sperm and dependence on dietary antioxidants to inhibit these detrimental effects.

Effect of long-term dietary beta-carotene supplementation on sperm concentration and motility in an endangered amphibian

Dietary carotenoids have a high antioxidant capacity, so it has been hypothesised that carotenoid supplimentation will improve sperm production and quality by protecting sperm from oxidative damage. The effects of carotenoids on sperm have only been assessed in three vertebrate species, and evidence for improved sperm concentration and motility remains equivocal. One reason for this might be that in most studies there has not been an assessment of the effects of single carotenoid compounds over a range of doses. Applied research focused on developing ways to improve sperm quality could benefit the captive breeding and conservation of threatened species. The aim of the present study was to assess a dose-dependent effect of beta-carotene supplementation on sperm concentration and motility in the endangered booroolong frog (Litoria booroolongensis). Individuals were supplemented with one of four beta-carotene doses (0, 0.1, 1 and 10 mg/g) from hatching until sexual maturity (53 weeks). Sperm concentration was determined prior to activation, and percent sperm motility and sperm velocity were measured at 0, 3 and 6 h post-activation using computer-assisted sperm analysis. Unexpectedly, beta-carotene had no significant effect on sperm concentration, percent motility or velocity at any time point, providing no evidence for beneficial effects. Findings of the present study indicate there are likely to be species-specific differences in sperm production and motility that influence the risk of oxidative damage to sperm and dependence on dietary antioxidants to inhibit these detrimental effects.

The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: The Role of HO-1.

Nowadays, there is a growing interest in compounds derived from plants as potential raw materials for drug development. One of the most studied compounds is beta-carotene (BC). Several clinical studies can be found investigating the cardiovascular effects of BC, however, all these results are controversial. There is an increasing body of evidence showing that besides the well-known antioxidant properties, under strong oxidative circumstances, BC could become prooxidant as well. In this study, we investigated the effects of long-term, low- and high-dose BC treatment in ischemic/reperfused (ISA/REP) hearts isolated from Zucker diabetic fatty (ZDF) rats. The animals were treated with various daily doses of BC for 4 weeks and then hearts were isolated and subjected to 30 min of global ischemia (ISA) followed by 120 min of reperfusion (REP). Blood glucose levels were measured before, after two weeks, and at the end of the treatment. In isolated hearts, the myocardial function was registered. At the end of the reperfusion period, the infarct size (IS) and heme oxygenase-1 (HO-1) expression were measured. The results showed that a low dose of BC treatment significantly improved postischemic recovery, which was reflected in a decreased IS. Interestingly, when BC was applied at high concentrations, the observed protective effects were lost. Although BC treatment increased HO-1 expression, we did not observe a better heart function and/or decreased IS in the high-dose-treated group. Glucose tolerance tests showed a concentration-independent decrease in blood glucose levels. Our results suggest that long-term, low-dose BC treatment could be effective in the treatment of type-2-diabetes and related cardiovascular diseases.

Antioxidants Attenuate Isolation- and L-DOPA-Induced Aggression in Mice.

Aggression is a major hallmark worldwide attributing negative traits in personality. Wide variety of antioxidants is used for the treatment of many ailments. The present study was conducted to evaluate the role of antioxidants such as ascorbic acid (15.42 and 30.84 mg/kg), beta carotene (1.02 and 2.05 mg/kg), vitamin E (2.5 and 5.0 mg/kg), and N-acetyl cysteine (102.85 and 205.70 mg/kg) in the treatment of aggression. Two aggression models (isolation induced aggression model and L-DOPA induced aggression model) were used in the study. Male albino mice (n = 330) were used in the study which were further subdivided into 11 groups (Group I-control, group II-diseased, group III-standard group, group IV–V treated with ascorbic, group VI–VII treated with beta carotene, group VIII–IX treated with vitamin E, group X–XI treated with N-acetyl cysteine for 14 consecutive days). Different biochemical markers (glutathione, superoxide dismutase, and catalase) were determined to evaluate the antioxidant potential in oxidative stress. High dose of vitamin E (5.0 mg/kg) was more effective to reduce the aggression in isolated animals while all other antioxidants produced dose-dependent anti-aggressive effect except N-acetyl cysteine which had marked anti-aggressive effect at low dose (102.75 mg/kg). Low doses of vitamin E (2.5 mg/kg) and N-acetyl cysteine (102.75 mg/kg) and high dose of beta carotene (2.05 mg/kg) were effective to prevent all aggression parameters in acute anti-aggressive activity against L-DOPA induced aggression. However, all test antioxidants were equally effective in chronic anti-aggressive studies against L-DOPA induced aggression. It may be concluded that selected antioxidants can reverse the aggression which is a key symptom of many neurological disorder.

P53 and ki67 as biomarkers in determining response to chemoprevention for oral leukoplakia.

We performed a randomized controlled chemoprevention trial of oral leukoplakia by administrating a low dose of beta-carotene and vitamin C supplements. 17% of subjects in the experimental arm (4/23) demonstrated clinical remission (complete or partial response) at completion of the trial. The objective of this study was to determine whether baseline expression of p53 and ki67 demonstrated any differences between those responding or not responding to our intervention. A secondary objective was to elucidate any relationship between dietary factors and clinical responses. For this biomarker study, we included all subjects in the experimental group (n = 23) who were non-smokers. Among 16 who completed the trial for 1 year of supplementation, there were four responders and 12 non-responders at 1-year follow-up. Following immuno-staining for p53 and ki67, the percentage of positive cell nuclei were analyzed as labeling index (LI). Expression of p53 was greater in basal layers than in para-basal layers. Mean para-basal LI of p53 was higher in non-responding (26.0) than in responding subjects (11.2) (P = 0.028). ki67 LIs were not significantly different in the two groups. Expression of p53 was inversely related to clinical response to the supplements. Other biomarkers that may recognize subject's responsiveness to chemoprevention require further study.

Antidepressant-like activity of beta-carotene in unstressed and chronic unpredictable mild stressed mice

The antidepressant-like activity of beta-carotene in Swiss young male albino mice subjected to chronic unpredictable mild stress was evaluated. Beta-carotene (50 and 100mg/kg, p.o.) and imipramine (15mg/kg, p.o.) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. Higher dose (100mg/kg) of beta-carotene and imipramine significantly decreased immobility period of mice in tail suspension test. These compounds significantly restored the reduced sucrose preference in stressed mice. There was no significant effect on locomotor activity of mice by the drugs. Beta-carotene significantly reversed stress-induced increase in brain catalase, monoamine oxidase (MAO-A), thiobarbituric acid-reactive substances (TBARS); and plasma nitrite and corticosterone levels; and increased stress-induced decrease in reduced glutathione levels. Thus, beta-carotene showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of MAO-A and oxidative stress. Its antidepressant-like activity in stressed mice might also be due to decrease in plasma corticosterone levels.

Meta-Regression Analyses, Meta-Analyses, and Trial Sequential Analyses of the Effects of Supplementation with Beta-Carotene, Vitamin A, and Vitamin E Singly or in Different Combinations on All-Cause Mortality: Do We Have Evidence for Lack of Harm?

Background and AimsEvidence shows that antioxidant supplements may increase mortality. Our aims were to assess whether different doses of beta-carotene, vitamin A, and vitamin E affect mortality in primary and secondary prevention randomized clinical trials with low risk of bias.MethodsThe present study is based on our 2012 Cochrane systematic review analyzing beneficial and harmful effects of antioxidant supplements in adults. Using random-effects meta-analyses, meta-regression analyses, and trial sequential analyses, we examined the association between beta-carotene, vitamin A, and vitamin E, and mortality according to their daily doses and doses below and above the recommended daily allowances (RDA).ResultsWe included 53 randomized trials with low risk of bias (241,883 participants, aged 18 to 103 years, 44.6% women) assessing beta-carotene, vitamin A, and vitamin E. Meta-regression analysis showed that the dose of vitamin A was significantly positively associated with all-cause mortality. Beta-carotene in a dose above 9.6 mg significantly increased mortality (relative risk (RR) 1.06, 95% confidence interval (CI) 1.02 to 1.09, I2 = 13%). Vitamin A in a dose above the RDA (> 800 µg) did not significantly influence mortality (RR 1.08, 95% CI 0.98 to 1.19, I2 = 53%). Vitamin E in a dose above the RDA (> 15 mg) significantly increased mortality (RR 1.03, 95% CI 1.00 to 1.05, I2 = 0%). Doses below the RDAs did not affect mortality, but data were sparse.ConclusionsBeta-carotene and vitamin E in doses higher than the RDA seem to significantly increase mortality, whereas we lack information on vitamin A. Dose of vitamin A was significantly associated with increased mortality in meta-regression. We lack information on doses below the RDA.BackgroundAll essential compounds to stay healthy cannot be synthesized in our body. Therefore, these compounds must be taken through our diet or obtained in other ways [1]. Oxidative stress has been suggested to cause a variety of diseases [2]. Therefore, it is speculated that antioxidant supplements could have a potential role in preventing diseases and death. Despite the fact that a normal diet in high-income countries may provide sufficient amounts of antioxidants [3,4], more than one third of adults regularly take antioxidant supplements [5,6].

No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene

Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men. There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007. The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture. Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97). This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.

Effects of β-carotene supplementation on adipose tissue thermogenic capacity in ferrets ( Mustela putorius furo)

We previously described that the intake of pharmacological doses of beta-carotene (BC) resulted in higher body weight gain in the ferret (Mustela putorius furo), an animal model that resembles human subjects in terms of intestinal BC absorption and metabolism. These results were some way unexpected considering the condition of BC as a vitamin A precursor and the previous data in rodents showing these compounds as thermogenic activators. Here, we aimed to characterise in the ferret whether the mentioned changes in body weight could be explained by changes in adipose tissue thermogenic capacity. We studied the effects of 6-month supplementation with BC (0.8 and 3.2 mg/kg per d) on adipose tissue morphology and uncoupling protein-1 (UCP1) content. BC supplementation resulted in higher body weight (the high dose), induced depot- and dose-dependent hypertrophy of white adipocytes, decreased the amount of brown-like multilocular adipocytes in the retroperitoneal depot and decreased UCP1 content in different fat depots. To ascertain whether BC effects could be mediated by retinoic acid (RA), 1 week supplementation with RA (0.25 and 25 mg/kg per d) was also studied. RA treatment resulted in a slight decrease in adiposity, decreased cell lipid accumulation and increased UCP1 content, suggesting that the effects of BC on thermogenic capacity are not through RA. In conclusion, RA, but not BC, may have in the ferret comparable effects with those described in rodents, whereas differences concerning BC and RA treatments may be attributable to the different BC metabolism in the present animal model with a lower conversion of BC to RA compared with rodents.

Comparative effects of β-carotene and fucoxanthin on retinol deficiency induced oxidative stress in rats

This study aimed at comparing antioxidant potential of fucoxanthin (FUCO) with beta-carotene in relieving lipid peroxidation (Lpx) caused by retinol deficiency (RD) in rats. RD rats (n = 45) were fed a dose of either beta-carotene (0.81 mumol) or FUCO (0.83 mumol). Plasma and liver lipid peroxide levels and activity of antioxidant enzymes catalase (CAT) and glutathione transferase (GST) were measured for 8 h. Results revealed that RD increased (P < 0.05) Lpx in plasma and liver by 34.3% and 19.4%, while the CAT activity in plasma (89%) and liver microsomes (91%) and GST in liver homogenate (31%) and liver microsomes (30%) were decreased (P < 0.05) compared to control (rats fed basal diet). FUCO suppressed (P < 0.05) the Lpx level by 7-85% (plasma) and 24-72% (liver) as compared to beta-carotene (51-76%, 33-65%) over a period of 8 h. The activity of CAT in plasma and liver microsomes was higher (P < 0.05) in FUCO (90-95%, 85-93%) and beta-carotene (87-96%, 79-91%) groups as compared to RD group. Similarly, the activity of GST in liver and its microsomes was also elevated (P < 0.05) in FUCO (44-51%, 22-51%) and beta-carotene (19-54%, 30-43%) groups as compared to RD group. Results demonstrate that FUCO has greater potential than beta-carotene in modulating Lpx, CAT, GST in plasma and liver of RD rats.

Two common single nucleotide polymorphisms in the gene encoding β‐carotene 15,15′‐monoxygenase alter β‐carotene metabolism in female volunteers

The key enzyme responsible for beta-carotene conversion into retinal is beta-carotene 15,15'-monoxygenase (BCMO1). Since it has been reported that the conversion of beta-carotene into vitamin A is highly variable in up to 45% of healthy individuals, we hypothesized that genetic polymorphisms in the BCMO1 gene could contribute to the occurrence of the poor converter phenotype. Here we describe the screening of the total open reading frame of the BCMO1 coding region that led to the identification of two common nonsynonymous single nucleotide polymorphisms (R267S: rs12934922; A379V: rs7501331) with variant allele frequencies of 42 and 24%, respectively. In vitro biochemical characterization of the recombinant 267S + 379V double mutant revealed a reduced catalytic activity of BCMO1 by 57% (P<0.001). Assessment of the responsiveness to a pharmacological dose of beta-carotene in female volunteers confirmed that carriers of both the 379V and 267S + 379V variant alleles had a reduced ability to convert beta-carotene, as indicated through reduced retinyl palmitate:beta-carotene ratios in the triglyceride-rich lipoprotein fraction [-32% (P=0.005) and -69% (P=0.001), respectively] and increased fasting beta-carotene concentrations [+160% (P=0.025) and +240% (P=0.041), respectively]. Our data show that there is genetic variability in beta-carotene metabolism and may provide an explanation for the molecular basis of the poor converter phenotype within the population.

The Xanthophyll Composition of Biofortified Maize (Zea mays Sp.) Does Not Influence the Bioefficacy of Provitamin A Carotenoids in Mongolian Gerbils (Meriones unguiculatus)

Maize has been targeted for biofortification with provitamin A carotenoids through traditional breeding. Two studies were conducted in gerbils to evaluate factors that may affect provitamin A activity. Maize diets had equal theoretical concentrations of vitamin A (VA) assuming 100% bioefficacy. Study 1 ( n = 57) varied the ratio of beta-cryptoxanthin and beta-carotene but maintained the same theoretical VA. Study 2 ( n = 67) varied lutein and zeaxanthin. Other treatments were oil, VA, or beta-carotene doses. Serum and livers were analyzed for VA and carotenoids. In study 1, total liver VA did not differ among the maize groups. In study 2, total liver VA of the VA and maize groups were higher than controls ( P < 0.05). Conversion factors were 2.1-3.3 mug beta-carotene equivalents to 1 mug retinol. Twice the molar amount of beta-cryptoxanthin was as efficacious as beta-carotene and the proportion of beta-cryptoxanthin or xanthophylls did not appreciably change the VA value of biofortified maize.

A Randomized Controlled Trial for the Treatment of Oral Leukoplakia With the Aid of Chemopreventive Agents

The evidence base for an effective treatment of oral leukoplakia is limited. Although several options for treatment of oral leukoplakia are available, there is lack of consensus on the most appropriate methods of management and ways to minimize malignant transformation. It is hypothesized that high dietary intake of carotenoids may reduce human cancer. Observational studies on diet suggest that its role on cancer prevention effects is related to beta-carotene. Antioxidant nutrients are known to interact, and synergistic protective effect by carotenoids with vitamin C via an antioxidant pathway has been shown. The purpose of this study was to evaluate the utility of beta-carotene and vitamin C supplements for the treatment of oral leukoplakia among non smokers and to assess the efficacy of these chemo-preventive agents in clinical remission and preventing malignant transformation. A randomized double-blind controlled trial involving 46 Japanese subjects (25 males, 21 females, age: 66±8.9, age range: 38-80) with oral leukoplakia who had either never smoked or were ex-smokers was undertaken in 3 centers. Subjects were allocated either to the experimental arm (23 subjects; 10mg/day of beta-carotene and 500mg/day of vitamin C) or to the control arm (23 subjects; 50mg/day of vitamin C alone). The random allocation was performed centrally with stratification by blocking randomization according to presence or absence of dysplasia. Two in the experimental arm and one in the control arm did not receive allocated interventions. The supplements were continued over one year, and subjects followed up a further year. The serum levels of antioxidant micronutrients were measured. Scientific and ethical committees of the involved institutes approved the protocol for this study, and the written informed consent was obtained from all subjects prior to the allocation to the trial. Intention to treat analysis (ITT) was used for the analysis. During the intervention 5 in the experimental arm and 5 in the control arm dropped out. Among those 3 in the experimental arm and 4 in the control arm returned for follow up at close of study. Finally 40 subjects were analyzed. Based on the sample size calculation the power of the test has met 82%. The outcome of the clinical responses was analyzed by Fisher’s exact test for overall response rate (CR + PR). Cox proportional hazards model was used to estimate relative risk with 95% CI for the development of oral cancer. Among 19 in the experimental arm, 1 had complete remission (CR), 3 partial remission (PR), 14 no change (NC) and 1 progress disease (PD), and among 21 in the control arm 1 had PR, 16 NC and 4 PD. Three subjects with oral leukoplakia and +/- dysplasia in the control arm, so far have developed oral cancer at 11, 23 and 30 months periods from the onset of the intervention. The overall response rate was 21.1% in the experimental group and 4.8% in the control group (p =0.172). Relative risk adjusted for age, sex and dysplasia of oral cancer by the supplement of beta-carotene and vitamin C was 0.80 (95%CI: 0.56-1.14) (p =0.221). No untoward side effects have been noted. It is concluded that the supplemental low dose of beta-carotene and vitamin C was effective for neither clinical remission nor protection of cancer development statistically. Nevertheless the outcome suggests a benefit from their anti-oxidant effect for the management of potentially malignant disorders. Further large-scale intervention studies will be necessary with longer observation periods, and inclusion of biological and molecular assessments may provide useful intermediate endpoints for the evaluation of the future chemo-preventive studies.