Effect of dietary canthaxanthin and iodine on the production performance and egg quality of laying hens.

In this study, we aimed to evaluate the effect of canthaxanthin (CX) and iodine (I) on the production of laying hens, on counteracting debilitation of the vitelline membrane, and on inhibiting Salmonella growth in eggs stored at 30°C. Three hundred hens were reared in cages. Birds were divided into six feeding groups (10 hens × 5 repetitions) that were administered 0, 3 or 6 ppm of CX and 1 or 10 ppm of I with their diets. Laying rate, egg weights, and feed conversion ratios were controlled. The quality of fresh eggs was assessed in wks 25-26, 48-50 and 62-63 of hens lives. An additional batch of eggs was incubated at the temperature of 30°C, and egg quality changes were monitored on days 3, 6 and 9 of storage. Additionally, eggs collected from four experimental groups of hens whose diets had been iodated with 1 or 10 ppm of I and supplemented with 0 or 6 ppm of CX were infected under laboratory conditions with Salmonella, and incubated for 5 and 10 d. The laying rate, egg weights, and feed conversion ratio were significantly improved. Dietary inclusion of CX contributed to a higher resistance of the vitelline membrane of egg yolks, but only for fresh eggs. Vitelline membrane degradation during egg storage at 30°C was significantly counteracted by dietary inclusion of I at a dose of 10 ppm. The same I dose resulted in the complete inhibition of Salmonella growth until day 10 of incubation, but exclusively for eggs collected from 40-week-old hens. Dietary supplementation with 10 ppm of I was found to impart high level of resistance to the vitelline membrane against the growth of Salmonella in case of eggs stored at 30°C; therefore, I was found to be more beneficial by ensuring longer preservation than that of CX. However, dietary supplementation with CX was found to increase the resistance of vitelline membrane in fresh eggs.

Effects of maternal dietary canthaxanthin and 25-hydroxycholecalciferol supplementation on antioxidant status and calcium-phosphate metabolism of progeny ducks.

Three experiments were conducted to investigate the effects of maternal dietary canthaxanthin (CX) and 25-hydroxycholecalciferol (25-OH-D3) supplementation on antioxidant status and calcium-phosphate metabolism of progeny ducks. Cherry Valley duck breeders (38 wk old) were fed either a control diet or the same diet plus CX (6 mg/kg) and 25-OH-D3 (0.069 mg/kg) for 32 weeks. Experiments 1, 2, and 3 were conducted with progeny ducks hatched from eggs laid by duck breeder hens at 54, 62, and 70 wk of age, respectively. Progeny ducks from both maternal treatments were fed with the same NRC (1994) vitamin regimen starter (1 to 14 d) and finisher (15 to 35 d) diets in experiments 1 and 2, and fed with the same high vitamin regimen starter (1 to 14 d) and finisher (15 to 35 d) diets in experiments 3. High vitamin regimen had higher levels of all vitamins, except biotin, than the NRC (1994) vitamin regimen. In experiment 1, maternal CX and 25-OH-D3 increased (P < 0.05) shank pigmentation and tibiotarsus ash and tended to decrease (P < 0.1) liver total superoxide dismutase activity (T-SOD) of one-day-old progeny ducks; and increased (P < 0.05) shank pigmentation, decreased (P = 0.05) liver protein carbonyl, and tended to increase (P < 0.1) liver total antioxidant capacity (T-AOC) of 14-day-old progeny ducks. In experiment 2, maternal CX and 25-OH-D3 increased (P < 0.05) shank pigmentation and liver T-AOC and decreased (P < 0.05) liver protein carbonyl of one-day-old progeny ducks, but increased (P < 0.05) the serum phosphate level of 14-day-old progeny ducks. In experiment 3, maternal CX and 25-OH-D3 increased (P < 0.05) shank pigmentation of one-, 14-, and 35-day-old progeny ducks and tended to increase (P < 0.1) liver T-SOD and tibiotarsus ash, but decrease (P < 0.1) liver malondialdehyde of one-day-old progeny ducks. It can be concluded that progeny dietary high vitamin regimen could partially prevent maternal CX-derived progeny shank pigmentation from bleaching. Maternal CX- and 25-OH-D3-derived effects are influenced by the hen's age and progeny's dietary vitamin regimen.

A meta-analysis on the effect of canthaxanthin on egg production in brown egg layers.

A meta-analysis was conducted to evaluate the effect of the carotenoid canthaxanthin on production performance in layer hens. The data set contained 576 performance measurements from 34 trials. The trials were all conducted according to a similar experimental protocol from 1997 to 2012. The age of the animals ranged from 21 to 65 weeks. The experimental diets were predominantly wheat/SBM based, fed in mash form ad libitum. Depending on the trial and the treatment group considered, canthaxanthin supplementation was in the range of 0 to 8 mg/kg of feed.Using a linear mixed model regression applied to all 34 trials simultaneously, significant dose-dependent increases were found in egg yolk mass (+0.53% per ppm of canthaxanthin inclusion in the feed, P < 0.001), in egg mass (+0.47% per ppm, P = 0.0132), egg weight (+0.17% per ppm, P = 0.046), and in feed intake (+0.32% per ppm, P = 0.0054). A numerical increase was found in egg production (+0.28%, P = 0.14). The FCR decreased numerically (-0.24% per ppm, P = 0.36). The deposition of canthaxanthin in the egg yolk was 2.25 ppm per ppm of canthaxanthin in the feed (P < 0.001). It is concluded that in addition to egg yolk pigmentation, antioxidant effect, enhanced reproduction, and immune-modulation, canthaxanthin can significantly increase egg mass, thereby enhancing the productivity of the flock. Mechanisms relating to carotenoid metabolism and functions in avian species are a new research area that will require further investigation to explain the observed effects.

Effect of broiler breeders fed with corn or sorghum diet and canthaxanthin supplementation on production and reproductive performance.

This study was designed to evaluate the effect of corn or sorghum diet and canthaxanthin (CX) supplementation on performance in broiler breeders. A total of 440 females with similar body weight (BW) (3.71 ± 0.14 kg) and 60 roosters were placed in an open-sided house with 20 pens, randomly distributed in a factorial arrangement (2 × 2). There were 4 diets of 2 ingredients; corn (CO) or sorghum (SO) and 2 levels of CX; 6 mg/kg (CX) and 0 mg/kg (NCX) totaling 5 replicate pens of 22 females and 3 males each, from 42 to 65 wk, divided in 2 periods (from wk 42 to 53 and wk 54 to 65). Birds' BW was measured every 28 d and mortality rate was calculated at the end of trial. Egg production (%), egg specific gravity (g/cm3), egg weight (g), yolk weight (%), albumen weight (%), eggshell weight (%) and yolk colorimetric score were measured weekly. Incubation parameters were recorded in 12 incubations to evaluate hatching eggs, hatching (%), hatchability (%), fertility (%), weight of the chicks born and their quality. The BW, mortality, percentage of yolk and albumen weight, fertility and some incubation parameters were not affected (P > 0.05) by diets used. An increase in the egg production, hatching eggs, chicks born and first quality chick by hen at the second period were observed in CX breeder's diets (P = 0.0066; P = 0.0060; P = 0.0368; P = 0.0326). Egg specific gravity and eggshell weight were improved at the first period by SO+CX diet (P = 0.0138; P = 0.0209) and the same effect to egg weight, but at the second period (P = 0.0251). The CX was well absorbed from the diet and effectively transferred to the egg yolk, thereby increasing egg yolk pigmentation in the both periods (P < 0.0001). The CX supplementation in broiler breeder diets improved the productive and reproductive performance (laying% and hatchable eggs) at the second period, also to the both periods improved the egg yolk pigmentation.

Effect of maternal canthaxanthin and 25-hydroxycholecalciferol supplementation on the performance of ducklings under two different vitamin regimens.

This study investigated the effects of maternal canthaxanthin (CX, 6 mg/kg) and 25-hydroxycholecalciferol (25-OH-D3 , 0.069 mg/kg) supplementation on the performance of Cherry Valley ducklings under two different vitamin regimens. A total of 780 duck breeder females and 156 males were randomly allotted to two diets with or without the addition of the mixture of CX and 25-OH-D3 (CX+25-OH-D3 ) for 32 weeks. Ducklings (males and females separately) hatched from eggs laid at 24 weeks of the duck breeder trial were fed with a NRC vitamin regimen, and ducklings (males and females separately) hatched from eggs laid at 32 weeks of the duck breeder trial were fed with a HIGH vitamin regimen (had higher levels of all vitamins except biotin than NRC vitamin regimen), for 14 days. The results showed that, maternal CX+25-OH-D3 supplementation increased the shank pigmentation for 7-days post hatch in ducklings under a NRC vitamin regimen, and for 14-days post hatch in ducklings under a HIGH vitamin regimen. Growth performance, antioxidant status and serum phosphorus of ducklings under a NRC vitamin regimen were increased by maternal CX+25-OH-D3 supplementation; however, these positive effects were not observed in ducklings under a HIGH vitamin regimen. Males revealed increased growth performance in ducklings under both NRC and HIGH vitamin regimens. Sexual differences in shank pigmentation, antioxidant status, tibia strength and serum phosphorus were not consistent as they were dependent on maternal CX+25-OH-D3 status or dietary vitamin regimens. Data suggest that maternal CX+25-OH-D3 supplementation is important for starter ducklings under a NRC vitamin regimen, but not HIGH vitamin regimen.

Effects of Dietary Xanthophylls, Canthaxanthin and Astaxanthin on N-Methyl-N-nitrosourea-induced Rat Mammary Carcinogenesis.

BACKGROUND: Natural xanthophylls, canthaxanthin and astaxanthin are known to exhibit anticancer activity. However, the dietary effects of canthaxanthin and astaxanthin on N-methyl-N-nitrosourea (MNU)-induced mammary cancer remain controversial, and their mechanisms of action have not been clearly identified. MATERIALS AND METHODS: Three-week-old female Sprague-Dawley rats were fed a xanthophyll-free (basal diet) diet or experimental diets containing canthaxanthin or astaxanthin (0.04% and 0.4%) for 5 weeks (until 8 weeks of age), after which all rats were provided the basal diet (n=15 each). Rats were administered MNU at 6 weeks of age, and the incidence of mammary tumors at 20 weeks of age was compared. The expression of adiponectin in mammary adipose tissues taken at 7 weeks of age was also compared. RESULTS: Compared to the basal diet group, the 0.4% (but not the 0.04%) astaxanthin diet significantly reduced the incidence of palpable mammary carcinoma (92% vs. 42%; p<0.05), while the low and high canthaxanthin diets produced no significant inhibition. Adiponectin immunoblotting showed significantly higher expression in the 0.4% astaxanthin diet group, while the other groups were similar to the basal diet group. CONCLUSION: High concentrations of astaxanthin suppress MNU-induced mammary carcinoma. Changes in adiponectin may be involved in the mechanism of action.

The effects of canthaxanthin on porcine oocyte maturation and embryo development in vitro after parthenogenetic activation and somatic cell nuclear transfer.

The objective of this study was to examine the effects of canthaxanthin (Cx) treatment during in vitro maturation (IVM) of porcine oocytes on embryonic development after parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT), on intracellular glutathione (GSH) and reactive oxygen species (ROS) levels in mature oocytes, and on gene expression in both PA- and SCNT-derived blastocysts. To determine the optimal effective concentration of Cx, porcine oocytes were cultured in IVM medium supplemented with various concentrations (0, 20, 40 and 80 µM) of Cx for 22 hr. Compared to other groups, supplementation with 40 µM Cx significantly improved blastocyst formation rates after PA (p < .05), but no significant differences were observed among groups in total blastocyst cell numbers. Subsequently, oocytes were cultured in IVM medium supplemented with or without 40 µM Cx. Oocytes treated with 40 µM Cx showed significantly increased cleavage and blastocyst formation rates after SCNT compared to the control group (p < .05). Moreover, significantly increased intracellular GSH and reduced ROS levels were observed in the Cx-treated group (p < .05). In addition, both PA- and SCNT-derived blastocysts from the 40 µM Cx-treated group showed significantly increased mRNA expression of Bcl2 and Oct4 and decreased Caspase3 expression level (p < .05), when compared with the control group. PA-derived blastocysts from the 40 µM Cx-treated group also exhibited significantly decreased expression of Bax (p < .05). Our results demonstrated that treatment with 40 µM Cx during IVM improves the developmental competence of PA and SCNT embryos. Improvement of embryo development by Cx is most likely due to increased intracellular GSH synthesis, which reduces ROS levels in oocytes, and it may also positively regulate apoptosis- and development-related genes.

Antioxidant and lipid peroxidation activities in rats fed with Aspergillus carbonarius carotenoid.

Effect of feeding partially saturated canthaxanthin (PSC), purified from Aspergillus carbonarius mutant, was studied using four groups of female albino rats (n=6) for 4 weeks. While the control group received basal diet ad libitum, Groups I, II and III were fed with basal diet containing 50, 100 and 250 ppm PSC, respectively. PSC feeding did not cause any significant changes in food intake and there was no gain in body weight either. PSC included in the diet significantly decreased cholesterol in blood. There was 44.75% and 60.54% decrease in LDL-cholesterol in rats fed with 50 and 100 ppm carotenoid. Hepatic ascorbic acid content increased by 44.59% in rats fed with 50 ppm PSC. Dietary PSC at 250 ppm lowered lipid peroxides by 19.49%. Activities of antioxidant enzymes, glutathione transferase and catalase were significantly higher in serum and liver of PSC fed rats compared to the controls. The results suggested that PSC feeding can induce hypocholesterolmic and antioxidant properties in rats.

Impact of dietary carotenoid and packaging during frozen storage on the quality of rainbow trout (Oncorhynchus mykiss) fed carotenoids.

BACKGROUND: The storage life of frozen salmonids is often limited primarily by oxidation and flesh discolouration due to carotenoid degradation. The objective of this research was to determine the carotenoid changes and therefore the muscle colour modifications during 6 months of frozen storage (-18 °C) of whole rainbow trout fed astaxanthin (100 ppm) or canthaxanthin (80 ppm), kept under two different packagings: plastic film and cardboard box. RESULTS: After 6 months of frozen storage, the carotenoid type effect was seen for dry matter while there was no packaging material effect on carotenoid, total lipids, and TBARS contents of trout fillets. The time under frozen storage had an effect on carotenoid and TBARS fillet concentration. The carotenoid-type effect was noted for the four colour parameters (lightness difference, chroma difference, hue angle difference, and total colour difference) of rainbow trout fillet, while the packaging material effect was observed only for chroma. Frozen storage time had an effect on the four colour parameters of rainbow trout fillet. CONCLUSION: Carotenoid and packaging material effects were more marked for colour parameters than for biochemical parameters. In this study, as fish were frozen and stored as whole fish, fish skin provided good protection against oxidation.

beta-Carotene and canthaxanthin alter the pro-oxidation and antioxidation balance in rats fed a high-cholesterol and high-fat diet.

This study investigated the effects of beta-carotene and canthaxanthin on lipid peroxidation and antioxidative enzyme activities in rats fed a high-cholesterol, high-fat diet. Wistar rats were divided into six groups. Negative control group (group NC) received a high-fat (150 g/kg) diet; cholesterol control group (group CC) received a high-cholesterol (10 g/kg), high-fat diet. The other four groups were fed a high-cholesterol, high-fat diet supplemented with crystal beta-carotene (group BC), beta-carotene beadlet (group BB), canthaxanthin beadlet (group CX) or alpha-tocopherol (group AT). Blood and livers were collected for analysis after 6 weeks of feeding. Group BB had significantly lower hepatic thiobarbituric acid reactive substance (TBARS) and conjugated diene concentrations, whereas group CX had a significantly lower plasma TBARS concentration than did group CC. In erythrocytes, glutathione peroxidase activities were significantly greater in groups BC, BB and CX than in group CC. Moreover, compared with group CC, catalase activities were significantly greater in groups BB and CX, and superoxide dismutase (SOD) activity was significantly greater in group BB. In livers, SOD activities were significantly greater in groups BC, BB and CX, and glutathione reductase activities were significantly greater in groups BB and CX than in group CC. Compared with group CC, hepatic retinol and alpha-tocopherol concentrations were significantly greater in groups BC, BB and CX, whereas plasma and hepatic cholesterol concentrations were significantly lower in group BC. These findings suggest that beta-carotene and canthaxanthin altered the pro-oxidation and antioxidation balance and suppressed cholesterol-induced oxidative stress via modulation of antioxidant system and cholesterol metabolism.

Effect of soybean phospholipids on canthaxanthin lipoproteins transport, digestibility, and deposition in rainbow trout (Oncorhynchus mykiss) muscle.

This study was designed to assess the effect of dietary soybean phospholipids on canthaxanthin transport by serum lipoproteins and canthaxanthin muscle deposition in trout. Three groups of 12 immature trout in triplicate with a mean body weight of 130 g were fed with three experimental diets containing (1) canthaxanthin plus lecithin plus fish oil, (2) canthaxanthin plus lecithin, and (3) canthaxanthin alone, for 12 days. The two major lipoprotein classes in rainbow trout are high-density lipoproteins, which transport principally carotenoids present in the serum, and low-density lipoproteins, which are responsible for the transport of cholesterol, both independently of the administered diet. In addition, very low density lipoproteins are responsible for triglyceride transport in serum. Nevertheless, the amount of canthaxanthin in the serum increased when carotenoid was associated with phospholipids plus fish oil. When canthaxanthin is transported by lecithin plus fish oil, the amount of phospholipids, cantaxanthin, and cholesterol deposited in muscle increased but not significantly. The highest apparent canthaxanthin digestibility coefficient was obtained when canthaxanthin was carried by lecithin plus fish oil. The administration of canthaxanthin carried by phospholipids improved its accumulation in the muscle of rainbow trout. This accumulation could be enhanced if the time of administration of canthaxanthin is increased.

Tissue astaxanthin and canthaxanthin distribution in rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar).

A comparative investigation of tissue carotenoid distribution between rainbow trout, Oncorhynchus mykiss, and Atlantic salmon, Salmo salar, was undertaken to identify the relative efficiency of utilization of astaxanthin and canthaxanthin. Higher apparent digestibility coefficients (ADCs) (96% in trout vs. 28-31% in salmon; P<0.05), and pigment retention efficiencies (11.5-12.5% in trout vs. 5.5% in salmon; P<0.05), for both astaxanthin and canthaxanthin, were observed for rainbow trout. Astaxanthin deposition was higher than canthaxanthin in rainbow trout, while the reverse was true for Atlantic salmon, suggesting species-specificity in carotenoid utilization. The white muscle (95% in trout vs. 93% in salmon) and kidneys (0.5% in trout vs. 0.2% in salmon) represented higher proportions of the total body carotenoid pool in rainbow trout than in Atlantic salmon (P<0.05), whereas the liver was a more important storage organ in Atlantic salmon (2-6% in salmon vs. 0.2% in trout; P<0.05). The liver and kidney appeared to be important sites of carotenoid catabolism based on the relative proportion of the peak chromatogram of the fed carotenoid in both species, with the pyloric caecae and hind gut being more important in Atlantic salmon than in the rainbow trout. Liver catabolism is suspected to be a critical determinant in carotenoid clearance, with higher catabolism expected in Atlantic salmon than in rainbow trout.

Skin pigmentation evaluation in broilers fed natural and synthetic pigments.

Broiler carcass skin color is important in the United States and Mexico. This study evaluated the use of natural and synthetic pigments in broiler diets at commercial levels. Birds were fed natural or synthetic pigments at low or high levels, simulating US and Mexican commercial practices. Skin color was measured during live production (3 to 7 wk of age) and after slaughter and chilling. The natural pigments had consistently greater skin b* values (yellowness) than the synthetic pigments. The high levels produced greater skin b* values than the low levels, regardless of source. The synthetic pigments had a slower increase in skin b* but reached the same level as the natural low by 7 wk. There was no difference in skin a* values (redness) due to pigment source or level or the age of the bird. By 7 wk, all pigment sources approached plateau levels in the blood, but the synthetic pigment diet produced higher blood levels of yellow and red pigments than the natural pigment diets. Processing intensified skin yellowness and reduced skin redness. These data suggest that although synthetic pigments might have been absorbed better than natural ones, natural pigments were more efficient at increasing skin yellowness and there were only small differences between high and low levels for each pigment source. This finding may allow reduction in pigment use and feed cost to achieve the same skin acceptance by the consumer.

Effect of canthaxanthin content of the maternal diet on the antioxidant system of the developing chick.

1. Effects of canthaxanthin supplementation of the maternal diet on the antioxidant system of the developing chick were investigated. 2. Three hundred and twenty female broiler breeder birds were housed in one of 4 controlled environment rooms with 3 replicates for all treatments, with the exception of the control treatment of which there were 4 replicates. All birds received one of 5 diets: control low xanthophyll diet, or the same diet supplemented with 3, 6, 12 or 24 mg/kg canthaxanthin in the form of Carophyll Red. At 30 weeks of age 60 eggs from each of the 5 groups were incubated. At d 16 of the embryo development, at d 1 and d 7 posthatch tissue samples were collected and analysed by HPLC-based methods. 3. Canthaxanthin accumulation in the egg yolk was proportional to dietary content. Furthermore, at 12 to 24 mg/kg canthaxanthin was associated with an increase in gamma-tocopherol concentration in the egg yolk. Canthaxanthin was transferred from the egg yolk to the developing embryo and, as a result, its concentration in the liver of the embryo at 16 and in 1-d-old chicks was increased. Even at d 7 posthatch canthaxanthin concentration in the chicken liver was elevated. 4. Canthaxanthin supplementation of the maternal diet at 12 mg/kg was associated with an increased alpha-tocopherol concentration in the liver of 1-d-old chicks and resulted in decreased tissue susceptibility to lipid peroxidation. 5. Canthaxanthin supplementation at 6 to 24 mg/kg was also associated with a delay in alpha-tocopherol depletion from the liver for 7-d posthatch. As a result of the increased canthaxanthin and vitamin E concentrations in the liver of 7-d-old chicks, tissue susceptibility to lipid peroxidation decreased. 6. The results support an idea that dietary carotenoids can modulate antioxidant systems of the developing chicken.

Absorption of canthaxanthin by the rat is influenced by total lipid in the intestinal lumen.

In this study the effect of luminal lipid on the absorption of canthaxanthin (CTX) was investigated using the lymph duct cannulated rat. Treatments were emulsions designed to deliver increasing amounts of olive oil (10, 30, 50, 70, or 90 mg/h) and CTX (12.5 nmol/h). Emulsions were continuously infused into the duodenum for 12 h, and lymph was collected during the final 6 h of infusion for analysis. As the amount of lipid in the emulsion increased, a linear increase in the absorption of CTX was observed. The recovery of CTX in the lymph when infused with 10 mg/h olive oil was 14.2 +/- 1.2% and with 90 mg/h was 26.9 +/- 5.7%. The efficiency of CTX absorption nearly doubled by increasing the amount of lipid infused with CTX. The correlation between lipid load and CTX absorbed was r= 0.85. We conclude that luminal lipid load affects CTX absorption.

Lipid oxidation in fresh and spray-dried eggs enriched with omega3 and omega6 polyunsaturated fatty acids during storage as affected by dietary vitamin E and canthaxanthin supplementation.

A 2 x 2 x 2 factorial experiment was planned to study the influence of dietary fat source (linseed oil or sunflower oil) and dietary doses of alpha-tocopheryl acetate (alpha-TA) (0 or 200 mg/kg of feed) and canthaxanthin (CX) (0 or 5 mg/kg of feed) on fatty acid (FA) composition and lipid oxidation of fresh and spray-dried eggs. Dietary supplementation with alpha-TA and CX modified the levels of certain long-chain polyunsaturated FA (PUFA). Lipid oxidation in fresh eggs and spray-dried eggs at 0, 6, and 12 mo of storage was measured by the lipid hydroperoxide (LHP) and TBA values. The LHP and TBA values were up to 10 times higher in spray-dried eggs than in fresh eggs. The evolution of LHP and TBA values in spray-dried eggs showed that omega3 FA-enriched eggs were more susceptible to lipid oxidation than those enriched with omega6 FA. The omega-TA supplementation increased the lipid stability of enriched eggs and was very effective throughout the storage of spray-dried eggs. On the other hand, CX supplementation did not prevent lipid oxidation in PUFA-enriched eggs. Moreover, no synergistic effect between both compounds was detected.

Dose dependency of canthaxanthin crystals in monkey retina and spatial distribution of its metabolites.

PURPOSE: To establish the threshold level of canthaxanthin crystals in the retina of cynomolgus monkeys. To correlate the spatial distribution of all-trans canthaxanthin and its metabolites with the grade of crystals. METHODS: Monkeys were orally administered 0, 0.2, 0.6, 1.8, 5.4, 16.2, and 48.6 mg/kg body wt canthaxanthin daily for 2.5 to 3 years. A second group of monkeys were administered 200 and 500 mg/kg body wt/d for 5 years. Ophthalmoscopy, electroretinography (ERG), retina and carotenoid analysis were performed as previously reported. RESULTS: Crystals in the retina periphery were observed by ophthalmoscopy preterminally only in the extreme high doses of 200 to 500 mg/kg body wt/d. There were no adverse effects on visual functions as measured by ERG. Crystals in the peripheral retina, and/or in the macula, were detected microscopically in all canthaxanthin treated groups except at the lowest dose of 0.2 mg/kg body wt/d. The grade of crystals increased up to a dose of 16.2 mg/kg body wt/d. Dose-dependent increases in canthaxanthin content also were noted in the retina, the liver, and in plasma. All-trans canthaxanthin was the major compound in the peripheral and paracentral retina of very highly dosed animals, where its concentration correlated largely with the grade of inclusions. In the macula, 4'-OH-echinenone was the dominant canthaxanthin metabolite. CONCLUSIONS: The grade of crystals in monkey retinas was dose dependent with a threshold level at 0.6 mg canthaxanthin/kg body wt/d. It correlated in the retinal periphery with the concentrations of all-trans-canthaxanthin and in the macula with its metabolites.

Canthaxanthin supplementation alters antioxidant enzymes and iron concentration in liver of Balb/c mice.

The 4,4'-diketo-beta-carotene, canthaxanthin, alters tocopherol status when fed to Balb/c mice, suggesting an involvement of carotenoids in the modulation of oxidative stress in vivo. We investigated further the modifications induced by an oral administration of canthaxanthin on lipid peroxidation, antioxidant enzymes and iron status in liver of Balb/c mice. Female 6-wk-old Balb/c mice were randomly divided into two groups (n = 10/group). The control group (C) received olive oil alone (vehicle) and the canthaxanthin-treated group (Cx) received canthaxanthin at a dose of 14 microg/(g body wt.d). The 15-d canthaxanthin treatment resulted in carotenoid incorporation but did not modify lipid peroxidation as measured by endogenous production of malondialdehyde (MDA). However, glutathione peroxidase activity was 35% lower (P<0.01) and catalase (59%, P<0.005) and manganese superoxide dismutase (MnSOD) (28%, P<0.05) activities were higher in canthaxanthin-treated mice than in controls. Moreover, carotenoid feeding caused a significant (P<0.05) overexpression of the MnSOD gene; mRNA levels of the enzyme were greater in treated mice than in controls. Concomitantly, a 27% (P<0.05) greater iron concentration was found in liver from canthaxanthin-treated mice compared with controls. These findings support the hypothesis that canthaxanthin alters the protective ability of tissues against oxidative stress in vivo.

A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo.

The anticancer activities of beta-carotene, astaxanthin and canthaxanthin against the growth of mammary tumors were studied in female eight-wk-old BALB/c mice. The mice were fed a synthetic diet containing 0, 0.1 or 0.4% beta-carotene, astaxanthin or canthaxanthin. After 3 weeks, all mice were inoculated with 1 x 10(6) WAZ-2T tumor cells into the mammary fat pad. All animals were killed on 45 d after inoculation with the tumor cells. No carotenoids were detectable in the plasma or tumor tissues of unsupplemented mice. Concentrations of plasma astaxanthin (20 to 28 mumol/L) were greater (P < 0.05) than that of beta-carotene (0.1 to 0.2 mumol/L) and canthaxanthin (3 to 6 mmol/L). However, in tumor tissues, the concentration of canthaxanthin (4.9 to 6.0 nmol/g) was higher than that of beta-carotene (0.2 to 0.5 nmol/g) and astaxanthin (1.2 to 2.7 nmol/g). In general, all three carotenoids decreased mammary tumor volume. Mammary tumor growth inhibition by astaxanthin was dose-dependent and was higher than that of canthaxanthin and beta-carotene. Mice fed 0.4% beta-carotene or canthaxanthin did not show further increases in tumor growth inhibition compared to those fed 0.1% of each carotenoid. Lipid peroxidation activity in tumors was lower (P < 0.05) in mice fed 0.4% astaxanthin, but not in those fed beta-carotene and canthaxanthin. Therefore, beta-carotene, canthaxanthin and especially astaxanthin inhibit the growth of mammary tumors in mice; their anti-tumor activity is also influenced by the supplemental dose.