Evaluation of the bioaccessibility of a carotenoid beadlet blend using an in vitro system mimicking the upper gastrointestinal tract.

The release characteristics of a unique blend of carotenoid beadlets designed to increase bioavailability were tested using the dynamic gastrointestinal model TIM-1. Individual carotenoid bioaccessibility peaks were observed over approximately 3-4 hr in the order of lutein and zeaxanthin first, followed by lycopene, and then finally α- and ß-carotene; when tested as a beadlet blend or when the beadlets were compressed into tablets. Bioaccessibility measurements of 7%-20% were similar to those previously reported in literature and comparable between the two formulations, beadlet blend and tablet formulations. Total recovery of carotenoids from all compartments ranged from 70% to 90% for all carotenoids, except lycopene where almost 50% was unrecoverable after digestion in the TIM system.

Role of ingestible carotenoids in skin protection: A review of clinical evidence.

Carotenoids, a class of phytonutrients, have been well established to boost skin's innate resistance against ultraviolet (UV) B-induced erythema (sunburn). Many of the published clinical studies thus far have focused on the measurement of erythema as the primary clinical indicator of skin protection against UVB radiation. More recent studies have shown that carotenoid supplementation provides even more skin protection than previously shown as new clinical and molecular endpoints beyond UVB-induced erythema have been reported. These recent studies have demonstrated that carotenoids also provide photoprotection against UVA-induced pigmentation and inhibit molecular markers of oxidative stress such as intercellular adhesion molecule 1, heme oxygenase-1, and matrix metalloproteinases 1 and 9. This article provides a comprehensive review of the published clinical evidence on skin benefits of carotenoids in the last five decades and indicates new perspectives on the role of ingestible carotenoids in skin protection.

Evidence for decreased interaction and improved carotenoid bioavailability by sequential delivery of a supplement.

Despite the notable health benefits of carotenoids for human health, the majority of human diets worldwide are repeatedly shown to be inadequate in intake of carotenoid-rich fruits and vegetables, according to current health recommendations. To address this deficit, strategies designed to increase dietary intakes and subsequent plasma levels of carotenoids are warranted. When mixed carotenoids are delivered into the intestinal tract simultaneously, competition occurs for micelle formation and absorption, affecting carotenoid bioavailability. Previously, we tested the in vitro viability of a carotenoid mix designed to deliver individual carotenoids sequentially spaced from one another over the 6 hr transit time of the human upper gastrointestinal system. We hypothesized that temporally and spatially separating the individual carotenoids would reduce competition for micelle formation, improve uptake, and maximize efficacy. Here, we test this hypothesis in a double-blind, repeated-measure, cross-over human study with 12 subjects by comparing the change of plasma carotenoid levels for 8 hr after oral doses of a sequentially spaced carotenoid mix, to a matched mix without sequential spacing. We find the carotenoid change from baseline, measured as area under the curve, is increased following consumption of the sequentially spaced mix compared to concomitant carotenoids delivery. These results demonstrate reduced interaction and regulation between the sequentially spaced carotenoids, suggesting improved bioavailability from a novel sequentially spaced carotenoid mix.

A multicarotenoid beadlet for human nutrition - proof of concept of in vitro timed release.

Since the 1980's when the predominate focus of study and use of carotenoids in human nutritional formulations was solely on beta-carotene, there has been a steady increase in research aimed to understand the role of a wide variety of carotenoids in human health. This work has increasingly demonstrated the benefits of a number of carotenoids, and there has been a corresponding increase in the number of carotenoids provided in nutritional supplements (multicarotenoids). Numerous published observations in both human and animal studies suggest significant interaction and competition between various carotenoids during absorption and metabolism, resulting in the inhibition of uptake of one over the other. This competition has the end result of reducing the beneficial effects of the inhibited carotenoid. To limit such competition and maximize carotenoid uptakes, a layered beadlet was designed to release a defined ratio of carotenoids sequentially. Preliminary dissolution testing is presented showing the release profile in simulated digestive conditions of a combination of beta-carotene, alpha carotene, lutein, zeaxanthin, lycopene and astaxanthin derived from natural sources. Comparison is made to an immediate release beadlet formulation using the same combination of carotenoids. These results will be used to guide proof of concept clinical testing for effectiveness in humans.

Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats.

Anorexia that accompanies cellular dehydration in rats (DE-anorexia) offers a relatively simple model for investigating the functional organization of neural mechanisms that can suppress feeding during dehydration. Previous studies strongly suggest that the inputs that drive ingestive behavior control neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA) remain active during DE-anorexia. Here we examine whether these two regions retain their sensitivity to neuropeptide Y (NPY). NPY is an important component in two major feeding-related inputs from the arcuate nucleus and the hindbrain. We found that intake responses to NPY injections in the LHA and PVH were suppressed in DE-anorexia, but the PVH remained less sensitive to the effects of NPY than the LHA in DE-anorexic animals. Indeed the higher dose of NPY (238 pmol) completely overcame shorter periods of DE-anorexia when injected into the LHA but not the PVH. However, the latency to eat after NPY injections remained unchanged from control animals, regardless of NPY dose, injection location, or intensity of anorexia. Furthermore, the onset and size of the strong and rapidly induced compensatory feeding that follows the return of water to DE-anorexic animals was also unaffected by any NPY injections. These data support the hypothesis that DE-anorexia develops as a consequence of the premature termination of regularly initiated meals, which perhaps involves processes that alter the sensitivity of satiety mechanisms downstream to the PVH and LHA.

A high-sugar/low-fiber meal compared with a low-sugar/high-fiber meal leads to higher leptin and physical activity levels in overweight Latina females.

Acute effects of high-sugar/low-fiber meals vs low-sugar/high-fiber meals on hormones and behavior were studied in 10 overweight Latina females, age 11 to 12 years, using a crossover design. In this exploratory pilot study, participants arrived fasted at an observation laboratory on two occasions and randomly received either a high-sugar/low-fiber meal or a low-sugar/high-fiber meal at each visit. Glucose, insulin, and leptin were assayed from serum drawn at 0, 15, 30, 60, 90, and 120 minutes. Ad libitum snacks were provided at 120 minutes. Physical activity was measured using an observational system that provides data on time spent lying down, sitting, standing, walking, and in vigorous activity. Data were collected between March 2005 and July 2006. In the high-sugar/low-fiber condition, glucose and leptin levels decreased more slowly, glucose levels were higher at 60 minutes (111.2 mg/dL vs 95.4 mg/dL, P=0.03), and leptin levels were higher at 90 minutes (49.3 ng/mL vs 46.7 ng/mL, P=0.017) than in the low-sugar/high-fiber condition. Meals did not affect insulin or ad libitum dietary intake. Sitting, standing, lying down, and vigorous activity differed by condition, but not walking. Participants were significantly more active in the first 30 to 60 minutes after the high-sugar/low-fiber meal, but after 60 minutes there was a trend for activity to be lower after the high-sugar/low-fiber meal vs the low-sugar/high-fiber meal. High-sugar meals sustain glucose and leptin levels longer, which may play an important role in modulating levels of physical activity in this group at high risk for obesity-related disease.

The role of hypothalamic ingestive behavior controllers in generating dehydration anorexia: a Fos mapping study.

Giving rats 2.5% saline to drink for 3-5 days simply and reliably generates anorexia. Despite having the neurochemical and hormonal markers of negative energy balance, dehydrated anorexic rats show a marked suppression of spontaneous food intake, as well as the feeding that is usually stimulated by overnight starvation or a 2-deoxy-d-glucose (2DG) challenge. These observations are consistent with a dehydration-dependent inhibition of the core circuitry that controls feeding. We hypothesize that this inhibition is directed at those neurons in the paraventricular nucleus and lateral hypothalamic area that constitute the hypothalamic "behavior controller" for feeding rather than their afferent inputs from the arcuate nucleus or hindbrain that convey critical feeding-related sensory information. To test this hypothesis, we mapped and quantified the Fos-immunoreactive response to 2DG in control and dehydrated rats drinking 2.5% saline. Our rationale was that regions showing an attenuated Fos response to 2DG in dehydrated animals would be strong candidates as the targets of dehydration-induced suppression of 2DG feeding. We found that the Fos response to combined dehydration and 2DG was attenuated only in the lateral hypothalamic area, with dehydration alone increasing Fos in the lateral part of the paraventricular nucleus. In the arcuate nucleus and those regions of the hindbrain that provide afferent inputs critical for the feeding response to 2DG, the Fos response to 2DG was unaffected by dehydration. Therefore, dehydration appears to target the lateral hypothalamic area and possibly the lateral part of the paraventricular nucleus to suppress the feeding response to 2DG.