RNA-Seq analysis of the pyloric caecum, liver, and muscle reveals molecular mechanisms regulating fillet color in rainbow trout.

BACKGROUND: The characteristic pink-reddish color in the salmonids fillet is an important, appealing quality trait for consumers and producers. The color results from diet supplementation with carotenoids, which accounts for up to 20-30% of the feed cost. Pigment retention in the muscle is a highly variable phenotype. In this study, we aimed to understand the molecular basis for the variation in fillet color when rainbow trout (Oncorhynchus mykiss) fish families were fed an Astaxanthin-supplemented diet. We used RNA-Seq to study the transcriptome profile in the pyloric caecum, liver, and muscle from fish families with pink-reddish fillet coloration (red) versus those with lighter pale coloration (white). RESULTS: More DEGs were identified in the muscle (5,148) and liver (3,180) than in the pyloric caecum (272). Genes involved in lipid/carotenoid metabolism and transport, ribosomal activities, mitochondrial functions, and stress homeostasis were uniquely enriched in the muscle and liver. For instance, the two beta carotene genes (BCO1 and BCO2) were significantly under-represented in the muscle of the red fillet group favoring more carotenoid retention. Enriched genes in the pyloric caecum were involved in intestinal absorption and transport of carotenoids and lipids. In addition, the analysis revealed the modulation of several genes with immune functions in the pyloric caecum, liver, and muscle. CONCLUSION: The results from this study deepen our understanding of carotenoid dynamics in rainbow trout and can guide us on strategies to improve Astaxanthin retention in the rainbow trout fillet.

Evaluation of saturated and unsaturated fat with vitamin A or beta-carotene supplementation in nursery pigs.

One hundred and fifty-two nursery pigs (PIC, Hendersonville, TN) were randomly assigned to mix sex pens and one of six dietary treatments in a 3 × 2 factorial. Diets included no added fat, 3% added choice white grease, or 3% added soy oil with either a supplemented vitamin A (for a total of 11,640 IU vitamin A/kg, Rovimix A 1000, DSM, Parsippany, NJ, US) or beta-carotene (for a total of 8,708 IU vitamin A/kg equivalent, Rovimix ß-Carotene 10%, DSM). Pigs were given a 3-d adaptation period upon arrival. Pigs were weighed at the start of the study and at the end of each phase. A blood sample was taken from one pig per pen at the start and end of the study. Tissues were collected from eight pigs at the start of the study and six pigs per treatment at the end of the study. Data were analyzed via the GLIMMIX procedure in SAS 9.4 (SAS Inst., Cary, NC). Pen was the experimental unit, and repeated measures were used for growth performance and blood parameters. There was no fat by supplement interaction (P > 0.05) on body weight (BW), but there was a tendency (P = 0.054) for heavier BWs when soy oil was added to diets. There was no difference (P > 0.05) in average daily feed intake or average daily gain (ADG). There was an improved gain:feed (P = 0.02) when pigs were fed choice white grease over no added fat. There were time differences (P < 0.05) for plasma vitamins A (retinol), D (25 hydroxy vitamin D3), and E (alpha-tocopherol). Vitamin A and D values were higher at the end of the study, whereas vitamin E values were lower at the end of the study. The choice white grease diets had the highest (P < 0.05) plasma vitamins D and E (6.74 ng/mL and 2.87 ppm, respectively). Pigs supplemented with vitamin A had higher (P < 0.05) hepatic vitamin A than pigs supplemented with beta-carotene (19.9 vs. 15.6 ppm, respectively). There were no differences (P < 0.05) between immunoglobulins G and M or mRNA abundance of select genes (retinol binding protein 2, alcohol dehydrogenase class 1, lecithin retinol acyltransferase phosphatidylcholine-retinol O-acyltransferase, and beta-carotene oxygenase 1). In conclusion, fat inclusion level and type, with either vitamin A or beta-carotene supplementation, did not affect the overall nursery pig growth performance. The addition of fat resulted in an increase in ADG and BW. Diets with choice white grease had the highest plasma vitamins D and E, and supplemental vitamin A increased hepatic vitamin A.

Fabricating pectin and chitosan double layer coated liposomes to improve physicochemical stability of beta-carotene and alter its gastrointestinal fate.

To improve storage stability and gastrointestinal (GI) stability of liposomes, pectin and chitosan double layer coated liposome (P-C-L) was proposed and optimized using electrostatic deposition technique. The physical-chemical properties and GI fate of the carrier were then investigated in comparison to that of chitosan coated liposomes (C-L) and un-coated liposomes (L). The results showed P-C-L was successfully prepared at 0.2 % chitosan and 0.06 % pectin. It was hydrogen bonds between the amino groups in chitosan and liposomal interfacial region, and the interaction between the carboxyl groups in pectin layer and amino groups in chitosan layer maintained the structure of P-C-L after absorption by electrostatic interaction. The double layer coatings could improve chemical stability of the encapsulated ß-carotene (ßC), as well as the thermal stability of liposomes. What's more, the permeability of liposomal bilayers and ßC release mechanism in simulated GI fluids was changed by the polymer coating. P-C-L exhibited better controlled release for ßC than C-L and L, and displayer beneficial effect on delivering bioactive agents passing through intensity tract. This may assistant developing more efficient delivery system for bioactive agent.

Effects of ß-carotene supplementation in the diet of laying breeder hens on the growth performance and liver development of offspring chicks.

This experiment was conducted to evaluate the growth performance, growth regulating factors, and liver morphology of chicks hatched from egg-laying breeding hens dietary supplemented with additives (ß-carotene). Hy-line breeding hens were allocated into three groups with three replicates/group. The dietary treatments were as follows: basal diet as a control (Con), basal diet supplemented with 120 (ßc-L) or 240 (ßc-H) mg/kg of ß-carotene diet. After 6 weeks, the eggs were collected and incubated. The hatched chicks were fed the same diet. The results showed that chicks in the ßc-L group increased in body weight at 21 days (p < 0.01). At 42 days, chicks in the ßc-H group showed a significant increase in tibia length (p < 0.05). The liver index increased in the ßc-L and ßc-H groups at 7 days (p < 0.05). Serum HGF (7, 14, 21, and 42 days) and leptin (14 days) were significantly increased in the group supplemented with ßc. Hepatic GHR (14 days), IGF-1R (14 days), and LEPR (21 days) mRNA expression were significantly increased. In addition, there was an increase in PCNA-positive cells in the liver of chicks in the ßc group. In conclusion, the addition of ß-carotene to the diet of laying breeder hens was more advantageous in terms of growth performance and liver development of the offspring.

The evaluation of the supplementation of vitamin A, beta-carotene, and oxidized beta-carotene in prepubertal gilts.

Finishing pigs (N = 224; 28.66 ± 1.90 kg bodyweight) were randomly assigned across 56 pens of either four barrows or gilts, and assigned to one of four diets: control (7,656 IU vitamin A/kg), control supplemented with vitamin A (4.36 ppm, Rovimix A 1000, DSM, Parsippany, NJ, USA), control supplemented with beta-carotene (163.28 ppm, Rovimix ß-Carotene 10%, DSM, Parsippany), or control supplemented with oxidized beta-carotene (40 ppm; 10% active ingredient, Avivagen, Ottawa, ON, Canada). Pigs and feeder weights were obtained at the start of the study (d 0), and end of each phase (d 21, 42, and 63). A subset of gilts had a blood sample taken via jugular venipuncture on d 0, a blood sample and vaccinations of Lawsonia intracellularis and porcine circovirus type 2 (PCV2) on d 18, a blood sample and booster vaccination of PCV2 on d 39, a blood sample on day 60, and a final blood sample on day 63. Gilts were euthanized at the end of the study to obtain a liver (entire right lobe) and a jejunum sample (15.24 cm at 10% of length). Additionally, the second and fourth right anterior mammary were collected to assess anterior mammary tissues. Data were analyzed in SAS 9.4 (Statistical Analysis System, Cary, NC) via GLIMMIX procedure. Oxidized beta-carotene supplementation increased (P = 0.02) ADG across phases over vitamin A supplementation, although there were no differences (P = 0.18) in the body weight of pigs. There was no effect (P > 0.05) of diet on plasma or hepatic retinol, IgG or IgM levels, or immune cell presence in developing mammary tissue. Supplemented vitamin A tended (P = 0.05) to increase the mRNA abundance of retinol binding protein in the jejunum, but other mRNA abundance for genes (alcohol dehydrogenase class 1, lecithin retinol acyltransferase phosphatidylcholine-retinol O-acyltransferase, and beta-carotene oxygenase 1) were not affected (P > 0.05) by dietary treatments. A diet by time interaction (P = 0.04) was noted for the circovirus S/P ratio, where vitamin A supplementation had the best ratio compared to other diets. Analyzed titer levels for the circovirus vaccine had an interaction (P < 0.01) for diet by time, where vitamin A supplementation had the highest titer at the end of the study. Thus, pigs supplemented with oxidized beta-carotene had an improved ADG over vitamin A supplemented pigs, but pigs supplemented with vitamin A seemed to have an improved immune status.

Vitamin A, beta-carotene, and oxidized beta-carotene were supplemented to finishing pigs to determine if feeding vitamin A, beta-carotene, or oxidized beta-carotene influences growth performance and the proliferation of immune cell populations in the developing mammary gland in prepubertal gilts. When evaluating overall growth parameters, there were no differences across the dietary treatments and no differences in the circulating immunoglobulin production. Supplementing vitamin A did increase the amount of retinol binding protein that was expressed in the small intestine. Pigs supplemented with oxidized beta-carotene did have an increase in average daily gain (ADG) during a health challenge over pigs supplemented with vitamin A. However, gilts that received vitamin A supplementation had an improved sample-to-positive ratio (S/P ratio) and titer response to porcine circovirus 2 vaccines, indicating that vitamin A supplemented gilts have an improved immune response to vaccinations.

Evaluation of oxidized beta-carotene on sow and piglet immune systems, sow reproductive performance, and piglet growth.

This study aimed to determine if supplementation of oxidized-beta carotene (OxC-Beta) improved sow reproductive performance, litter growth performance, vitamin A status, and ability to alter immune cells abundance in sows and piglets, subsequent litter performance, and nursery growth performance. On approximately day 60 of gestation and through the lactation period, 194 sows (blocked by parity) were assigned to a common gestation diet or the common diet supplemented with 80 ppm oxidized beta-carotene (OxC-Beta, Aviagen, Ottawa, ON, Canada). A subset of sows (N = 54 per treatment) were sampled for blood and body weight recorded at the beginning of the study, farrowing, and weaning. A blood sample was taken from a subset of piglets at birth and weaning, and all piglet weights were recorded. Blood was analyzed for vitamin A as retinol concentrations and immunoglobulin G (IgG) and immunoglobulin M (IgG) levels were assessed from the sow's blood. Twelve pigs (N = 6 per treatment) were euthanized at birth and weaning. The livers were collected and analyzed for the Kupffer cell phagocytic activity through flow cytometry. Whole blood was analyzed via flow cytometry for cluster of differentiation (CD335, CD8, and CD4). Colostrum during farrowing and milk at weaning were analyzed for IgG and IgA concentrations. Data were analyzed via SAS 9.4 using MIXED and frequency procedures where appropriate. No differences (P > 0.05) between dietary treatments were observed in sow reproductive performance, feed intake, wean to estrus interval, or piglet growth performance. No differences (P > 0.05) were observed in the plasma or liver for vitamin A. No differences (P > 0.05) were observed in the composition of the colostrum or milk. No immunological differences (P > 0.05) were observed in the piglets' liver and blood or sow antibodies in colostrum and milk. The supplementation of OxC-Beta did (P < 0.05) decrease IgM and tended (P < 0.10) to decrease IgG in sow plasma. No differences (P > 0.05) were observed in the reproductive performance of subsequent litter information from the sows. Gilt litter weaning weight and feed intake were reduced (P < 0.05) compared to sow performance. In conclusion, the supplementation of OxC-Beta at 80 ppm from day 60 of gestation through lactation does not affect the reproductive performance of sows, litter growth performance, vitamin A status, piglet immune status, and antibodies or composition in colostrum and milk.

Beta-carotene is a known antioxidant found in most red and orange-pigmented vegetables and has been documented to have health benefits. However, beta-carotene has been reported to gain oxygen molecules spontaneously, thus oxidizing it. Oxidized beta-carotene has been recognized to provide potential health benefits to animals, although its functions are independent of beta-carotene. Sows in this study were supplemented with an oxidized beta-carotene product to evaluate whether the product could improve reproductive performance, including the number of piglets born alive, piglet birth weight, weaning weight, sow milk quality, and immune function of both the sow and piglets. There were no significant findings between the reproductive performance or difference in colostrum and milk composition of the control sows and the sows supplemented with the product. There was also no difference in piglet growth between the two groups. The product did not affect the measured immune functions of the piglets. However, immunoglobulin G tended to decrease with the use of the product, and there was a decrease in immunoglobulin M. Overall, supplementing the oxidized beta-carotene product did not affect the reproductive performance of sows or the growth performance of piglets.

Effects of different vitamin A supplies on performance and the risk of ketosis in transition cows.

This experiment investigated the effects of feeding low and high supplies of vitamin A (VA) during the transition period on plasma metabolites, prevalence of ketosis, and early milk production. In a randomized complete block design, 42 prefresh Holstein cows and 21 heifers were blocked by parity and calving date and assigned to 1 of 3 dietary treatments (n = 21 per treatment unless noted): CON, a transition diet with supplemental VA (75,000 IU/d) to meet the requirement; LVA, a transition diet with no supplemental VA; or HVA, a transition diet receiving supplemental VA (187,500 IU/d) 2.5 times greater than the requirement. Experimental periods were prepartum (-14 d prepartum), postpartum (1 to 30 d in milk), and carryover period (31 to 58 d in milk; common lactating diet with adequate VA was fed). Differences in dry matter intake in the pre- and postpartum periods and milk yield were not detected among treatment. Milk fat, protein, and lactose yields were similar among treatments and not affected by VA. Somatic cell count increased linearly with increasing VA. Body weight and body condition score decreased postpartum, but no VA effect was observed. Plasma retinol concentrations (n = 10 per treatment) decreased at d 2 postpartum and increased as lactation progressed, but the concentrations were unaffected by treatment. Plasma ß-carotene (n = 10 per treatment) had a treatment by time interaction and its concentration decreased after parturition and remained low for 2 wk. Plasma fatty acids and ß-hydroxybutyrate did not differ among treatments. Milk retinol concentration and yield (n = 10 per treatment) increased as VA supply increased. Segmented neutrophils (%) decreased, and lymphocytes (%) increased in blood with increasing VA supply. In conclusion, providing different supplies of VA did not affect production, mobilization of body fat, and risk of ketosis; however, excessive VA supply may have negatively affected the immune response, in part contributing to increased milk somatic cell counts during early lactation.

The benefits of vitamin A as a complementary treatment for oncology patients: a systematic review.

PURPOSE: Vitamin A and its derivatives positively influence the differentiation of epithelia and other tissues and prevent the proliferation of preneoplastic and neoplastic cells. Vitamin A is therefore taken into account as a potential supporting factor in cancer therapy. METHODS: In November 2020, a systematic search was conducted searching five electronic databases (EMBASE, Cochrane, PsycINFO, CINAHL and Medline) to find studies looking at the effects of using vitamin A as a complementary therapy for cancer patients. From all 12,823 search results, 9 publications referring to 9 studies with 4296 patients were included in this systematic review. RESULTS: The patients treated with vitamin A were diagnosed with various cancers and stages. Outcome variables were overall survival of cancer, progression-free survival, occurrence of second primary tumours and recurrences, improvement of chronic radiation-induced proctopathy and side effects of vitamin A. For the most part, the studies had a limited methodological quality. In summary, it can be said that due to the methodological deficiencies of the studies, no concrete statement can be made regarding the prolongation of overall survival and progression-free survival. There is also no evidence of the benefit of vitamin A in the treatment of chronic radiation-induced proctopathy, which can be attributed to methodological deficiencies in the study, as well. In the studies that report on side effects, it becomes clear that side effects, such as mucocutaneous symptoms, temporary increase in liver enzymes and gastrointestinal side effects occur more frequently in the group with vitamin A intervention. CONCLUSION: The limited interpretability of the results due to the methodological deficiencies of the included studies does not allow a final statement on the benefits of vitamin A as a complementary treatment for cancer patients.

Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L.

Natural products have offered a number of exciting approaches in cancer treatment over the years. In this study, we investigated the prophylactic and therapeutic effects of the polyphenol-enriched fraction extracted from Myrtus communis (PEMC) on acute and chronic leukemia. According to the UHPLC-MSn, the fraction is rich in flavonoids. Protective activity of the PEMC was assessed by evaluating the antioxidant, anti-inflammatory, wound healing, and hemolysis potential in a series of in vivo and in vitro assays, while the therapeutic approach consisted of the evaluation of cytotoxic activity of the PEMC against HL60 and K562 leukemia cell lines. Safety of the fraction was also evaluated on a non-cancerous Vero cell line and by an acute toxicity test performed in mice. The PEMC demonstrated a significant anti-inflammatory and healing potential. The activities found at the dose of 100 mg/kg were better than those observed using a reference drug. The PEMC demonstrated a significant antioxidant effect and a specific cytotoxicity towards HL60 (IC50 = 19.87 µM) and K562 (IC50 = 29.64 µM) cell lines being non-toxic to the Vero cell line. No hemolytic activity was observed in vitro and no toxicity effect was found in mice. Thus, the PEMC has a pharmacological potential as both preventive and therapeutic agent. However, further research is necessary to propose its mechanism of action.

The association between dietary total antioxidant capacity and quality of nutrients with odds of colorectal cancer: A hospital-based case-control study.

BACKGROUND & AIMS: Dietary quality and patterns have been associated with reduced incidence and increased colorectal cancer (CRC) survival. Two validated scores representing the quality of diet defined respectively by their content in micronutrients (nutritional quality index (INQ)) and antioxidant (dietary antioxidant index (DAI)) were used for assessing dietary quality. INQ standardizes all micronutrients using the recommended values and adjusts nutrients intakes based on total energy. Major dietary antioxidants are standardized based on the global mean and then divided by the global standard deviation to calculate the DAI. We hypothesize that a quality diet with higher scores of DAI can reduce CRC odds. METHODS: In this hospital-based case-control study, 207 definite CRC cases and 220 controls met the inclusion criteria. Cases and controls were frequency-matched for age (±5 years) and sex. A 168-item semi-quantitative food frequency questionnaire was completed. Adjusted and unadjusted odds ratios (OR) and 95% confidence intervals (CI) were reported in logistic and multivariable regression models. RESULTS: DAI as a continuous (OR = 0.91, 95% CI: 0.85-0.98) and as a categorical (OR = 0.58, 95% CI: 0.37-0.92) variable and the INQs of vitamin A (OR = 0.30, 95% CI: 0.10-0.89), riboflavin (OR = 0.55, 95% CI: 0.32-0.94), magnesium (OR = 0.37, 95% CI: 0.18-0.77) and selenium (ORmultiple adjusted = 0.55, 95% CI: 0.36-0.86) in the regression crude models, and multivariable adjustments significantly have a protective association in reducing the odds of CRC (all p-values <0.05). CONCLUSIONS: It can be concluded that dietary antioxidants, including vitamins A, C, E, zinc, selenium, and manganese from a high-quality diet, including vegetables, whole grains, and fruits, can significantly reduce CRC incidence.

Once-Daily Low Inflammatory Foods Everyday (LIFE) Smoothie or the Full LIFE Diet Lowers C-Reactive Protein and Raises Plasma Beta-Carotene in 7 Days.

Serum C-reactive protein (CRP), a marker of systemic inflammation, is associated with increased risk for numerous inflammation-driven chronic diseases. A prior longitudinal study showed that the Low Inflammatory Foods Everyday (LIFE) diet, which is rich in dark green leafy vegetables (DGLV), lowered CRP over a mean follow-up period of 6 months. In this retrospective study, we investigate whether patients who consume the LIFE diet or their regular diet plus one component of the LIFE diet (LIFE smoothie), experience reductions in high-sensitivity CRP (hsCRP) in 7 days. Sixteen patients in a community practice met inclusion criteria. Patient compliance was assessed by patient interviews and measurements of beta-carotene, which is abundant in DGLV. Following the interventions, CRP decreased in both the LIFE diet (-0.47 mg/L, P = .02) and smoothie groups (-1.2 mg/L, P = .04). No statistically significant difference in reduction was observed between groups (P = .18). Plasma beta-carotene increased in both groups (+23.2, P = .02; +20.6, P = .006, respectively). These findings suggest that the LIFE diet or a regular American diet supplemented with the LIFE smoothie may quickly reduce systemic inflammation and the risk of many chronic diseases.

Association Between Beta-Carotene Supplementation and Mortality: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Aging is a phenomenon universally involving all organisms, genetically determined, and epigenetically influenced by the environment. Numerous observational studies have shown the positive impact of non-pharmacological approaches started in younger age on chronic conditions affecting the elderly health and survival. This meta-analysis aimed to investigate the effect of beta-carotene on the total and cause-specific mortality as reported by randomized controlled trials (RCTs). Methods: We searched Medline, Scopus, Web of Science, and CENTRAL Cochrane from inception to September 2021. Studies were eligible if enrolled adults with any health condition, compared beta-carotene supplements at any dose with placebo or no intervention, provided information on deaths from any cause, and were RCTs, in English. The risk of bias was assessed by the Cochrane risk of bias tool and the GRADE. Risk ratios and their 95% confidence intervals were used and a P-value less than 0.05 was considered statistically significant. Results: Among 3,942 articles searched, 44 articles on 31 RCTs, which included 216,734 total subjects, 108,622 in beta-carotene supplement groups, and 108,112 in the placebo or no-intervention groups, were involved in the final analyses. In a random-effects meta-analysis of all 31 trials, beta-carotene supplements were found to have no preventive effect on mortality (risk ratio 1.02, 95% confidence interval 0.98-1.05, I 2 = 42%). Further, the analysis showed no preventive effect on cancer, cardiovascular, cerebrovascular, and other mortality causes. Instead, beta-carotene supplementation significantly increased the risk of lung cancer mortality (RR 1.14, 95% CI 1.02, 1.27, I 2 = 3%) but decreased the risk of human immunodeficiency virus-related mortality (RR 0.55, 95% CI 0.33, 0.92, I 2 = 0). Conclusion: More studies should be performed to better define the role of beta-carotene on survival, to confirm or deny our results. Therefore, the possible beneficial or harmful effects of the beta-carotene supplementation on mortality must not be overstated. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259354], identifier [CRD42021259354].

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.

Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression.

Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in reducing lung cancer risk is lifestyle change, most patients favour the use of supplements, for example, rather than quitting smoking or following a healthy diet. To better understand the efficacy of such interventions, a systematic review was performed of data from randomized controlled trials concerning the influence of beta-carotene supplementation on lung cancer risk in subjects with no lung cancer before the intervention. The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06-1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08-1.35) and non-medics (RR = 1.18, 95% CI = 1.07-1.29). A meta-regression found no relationship between the beta-carotene supplementation dose and the size of the negative effect associated with lung cancer risk. Our findings indicate that beta-carotene supplementation has no effect on lung cancer risk. Moreover, when used as the primary chemoprevention, beta-carotene may, in fact, increase the risk of lung cancer.

ß-carotene regulates cancer stemness in colon cancer in vivo and in vitro.

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). ß-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133+CD44+ HCT116 and CD133+CD44+ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/ß-catenin signaling were examined. In addition, CD133+CD44+ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and ß-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133+CD44+ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/ß-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

Low Serum Vitamin D Status Is Associated with Incident Alzheimer's Dementia in the Oldest Old.

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer's dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies.

Genotype Effects on ß-Carotene Conversion to Vitamin A: Implications on Reducing Vitamin A Deficiency in the Philippines.

BACKGROUND: The study aimed to identify 2 beta-carotene 15,15'-monooxygenase (BCMO1) mutations, namely R267S and A379V, and determine their association with vitamin A status among Filipinos 6 to 19 years old respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. MATERIALS AND METHODS: This study followed cross-sectional design. Whole blood specimen was collected in the morning and was used as source of genomic DNA and serum for retinol concentration determination. Fisher exact test was performed to determine whether genotype frequencies were associated to retinol concentrations/vitamin A deficiency status. A level of P < .05 was identified as significant. RESULTS: A total of 693 Filipino children and adolescents were included. Of the 693, there were at least 7.6% who bear the combined mutations for R267S + A379V. Association analysis showed that an inverse relationship exists between the A379V TT variant and vitamin A status, although the exact role of these identified polymorphisms on retinol/carotenoid metabolism need to be confirmed in dedicated functional studies. CONCLUSION: This study has identified for the first time the presence of 2 nonsynonymous genetic variants/mutations in the coding region of BCMO1 gene. Interestingly, one of these 2 variants, the A379V T, was found to be associated with vitamin A status. It is, therefore, warranted to investigate the role of BCMO1 variants for the success of supplementation programs and fortification efforts among vulnerable populations in this region. Genetic variability should be considered for future provitamin A supplementation recommendations among children and adolescents in the Philippines.

Relationship between urinary cotinine and serum vitamin A levels in Korean adults: the Korea National Health and Nutrition Examination Survey (KNHANES), 2016-2018.

OBJECTIVE: To examine the relationship between urinary cotinine and serum vitamin A levels in Korean adults. METHODS: A total of 4445 adults (age ≥19 years) participating in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2016 to 2018 were classified by sex and as smokers/electronic cigarette users (SE) or non-smokers (NS). Data were analyzed using complex sample general linear models. RESULTS: There were no differences in dietary intake of vitamin A, carotene, or retinol between the SE and NS groups. Adjusted mean serum vitamin A levels were higher in the SE group compared with those in the NS group (0.63 mg/L vs 0.60 mg/L among men; 0.55 mg/L vs 0.51 mg/L among women). Among all participants, urinary cotinine and serum vitamin A levels were positively correlated (R2 = 0.037). However, no correlation was observed in either the SE or NS groups individually. In a model adjusted for age, body mass index, sex, frequency of binge drinking, and dyslipidemia, a stronger correlation was observed (R2 = 0.244). CONCLUSION: In Korean adults, urinary cotinine levels were positively associated with serum vitamin A levels. Mean serum vitamin A levels were significantly higher in the SE group compared with the NS group.

Neuroprotective Effects of Acrocomia aculeata Pulp Oil Microcapsules on Rats Subjected to Chronic Stress.

Acrocomia aculeata fruits are rich in monounsaturated fatty acid, ß-carotene, tocopherol, and other antioxidant compounds. The aim of our study was to investigate and compare the protective effects of A. aculeata pulp oil and microencapsulated pulp oil on brain oxidative damage induced by chronic restraint stress (CRS) in rats (cortex, hippocampus, and striatum). Thirty-six Wistar rats were divided into six treatment groups: C, P, and M groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively. The SC, SP, and SM groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively, and were then subjected to uninterrupted 6 h of CRS. After 21 days of testing, the rats were euthanized and the brain tissue of the groups was removed for evaluation for oxidative damage markers and antioxidant enzymes. Endpoints of oxidative stress (OS) markers (lipid peroxidation, protein carbonylation, and reduced glutathione [GSH]) and antioxidant enzymes (superoxide dismutase and catalase) were evaluated. By imposing chronic stress on rats, pulp oil and microcapsules of pulp oil induced positive antioxidant responses, mainly by increasing the GSH content, increasing the ability of neural tissues to deal with inherent OS, thus protecting against neurodegenerative diseases. The administration of A. aculeata pulp oil and microencapsulated pulp oil made the reversal of the oxidant parameters, which may protect the brain tissue of rats altered by CRS. The Clinical Trial Registration number: n° 1.008/2018 CEUA/UFMS.

Carotenoid deprivation and beta-carotene's effects on male and female turtle color.

Carotenoid-colored integuments commonly function as sexually selected honest signals because carotenoid pigments can be costly to obtain, ingest, absorb, metabolize or transport before being deposited into the integument. As such, carotenoid pigmentation is often sexually dichromatic, with males being more colorful than females. Sexual dichromatism may also occur in ultraviolet (UV) wavelengths, which is visible to organisms who possess UV-sensitive photoreceptors. The stripes and spots of painted turtles (Chrysemys picta) are carotenoid-based and reflect UV wavelengths. This research describes UV sexual dichromatism in painted turtles and shows how carotenoid deprivation changes spot and stripe color in male and female painted turtles. Adult turtles were fed a diet that was supplemented with carotenoids (i.e., C diet) or deprived of carotenoids (C-). Stripe and spot color were measured with UV-vis spectrometry, and blood was drawn from all turtles before and after the dietary treatment. HPLC analysis revealed five carotenoids (4 xanthophylls and beta-carotene) circulating in turtle blood. C-diet reduced yellow chroma and increased brightness of yellow and red stripes or spots, relative to the C diet, but there was no sexually dimorphic effect of carotenoid deprivation on color, nor did carotenoid deprivation affect UV reflectance. Carotenoid deprivation reduced all circulating carotenoids, but beta-carotene was the only pigment with a significant effect on post-experimental carotenoids, implying that changes in color were due in part to reduction in circulating levels of beta-carotene. Color generation appears to be complex in turtles and have dietary as well as non-dietary components.