Influence of observational study design on the interpretation of cancer risk reduction by carotenoids.

Recently published literature has been reviewed to determine whether lycopene, beta-carotene, alpha-carotene, and beta-cryptoxanthin are associated with reductions in cancer risk and whether study findings differ by study design. A total of 57 publications meeting pre-defined inclusion and exclusion criteria were identified, with the majority (55) being observational studies. None of the intervention studies supported a significant reduction in cancer risk with carotenoid (beta-carotene) supplementation. The majority of observational studies did not support significant reductions in cancer risk with increased carotenoid dietary intakes/circulating levels. A larger percentage of case-control studies supported significant associations between increased dietary intakes/circulating levels of carotenoids relative to prospective (cohort and nested case-control) studies. Compared to prospective studies, case-control studies cannot be used to establish temporality and may be more susceptible to selection and recall biases. Thus, diet-disease relationships suggested by case-control studies should ideally be confirmed by additional evidence from prospective studies.

Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection.

BACKGROUND: The amount of dietary fat required for optimal bioavailability of carotenoids in plant matrices is not clearly defined. OBJECTIVE: The objective was to quantify the appearance of carotenoids in plasma chylomicrons after subjects ingested fresh vegetable salads with fat-free, reduced-fat, or full-fat salad dressings. DESIGN: The subjects (n = 7) each consumed 3 salads consisting of equivalent amounts of spinach, romaine lettuce, cherry tomatoes, and carrots with salad dressings containing 0, 6, or 28 g canola oil. The salads were consumed in random order separated by washout periods of > or =2 wk. Blood samples were collected hourly from 0 to 12 h. Chylomicrons were isolated by ultracentrifugation, and carotenoid absorption was analyzed by HPLC with coulometric array detection. RESULTS: After ingestion of the salads with fat-free salad dressing, the appearance of alpha-carotene, beta-carotene, and lycopene in chylomicrons was negligible. After ingestion of the salads with reduced-fat salad dressing, the appearance of the carotenoids in plasma chylomicrons increased relative to that after ingestion of the salads with fat-free salad dressing (P < 0.04). Similarly, the appearance of the carotenoids in plasma chylomicrons was higher after the ingestion of salads with full-fat than with reduced-fat salad dressing (P < 0.02). CONCLUSIONS: High-sensitivity HPLC with coulometric array detection enabled us to quantify the intestinal absorption of carotenoids ingested from a single vegetable salad. Essentially no absorption of carotenoids was observed when salads with fat-free salad dressing were consumed. A substantially greater absorption of carotenoids was observed when salads were consumed with full-fat than with reduced-fat salad dressing.

Molecular factor analysis applied to collections of NMR spectra.

It is often useful to identify and quantify mixture components by analyzing collections of NMR spectra. Such collections arise in metabonomics and many other applications. Many mixtures studied by NMR can contain hundreds of compounds, and it is challenging to analyze the resulting complex spectra. We have approached the problem of separating signals from different molecules in complex mixtures by using self-modeling curve resolution as implemented by the alternating least-squares algorithm. Alternating least squares uses nonnegativity criteria to generate spectra and concentrations from a collection of mixture spectra. Compared to previous applications of alternating least squares, NMR spectra of complex mixtures possess unique features, such as large numbers of components and sample-to-sample variability in peak positions. To deal with these features, we developed a set of data preprocessing methods, and we made modifications to the alternating least-squares algorithm. We use the term "molecular factor analysis" to refer to the preprocessing and modified alternating least-squares methods. Molecular factor analysis was tested using an artificial data set and spectra from a metabonomics study. The results show that the tools can extract valuable information on sample composition from sets of NMR spectra.

Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6J mouse.

We have previously shown that the C57BL/6J (B6) mouse will develop obesity and diabetes if raised on a high-fat diet. Because high fat feeding is associated with hyperphagia, the present study was designed to separate the effects of fat from those of excess caloric consumption in this animal model. B6 mice were fed a low-fat diet (LF group) diet, high-fat diet (HF group) diet, or high-fat-restricted diet (HFR group), in which intake animals were pair-fed a high-fat diet to caloric level consumed by LF for 11 weeks. Within 3 weeks, HFR were significantly heavier than LF and, after 11 weeks, weight and glucose levels, but not insulin, were significantly increased in HFR when compared to LF. Body composition analysis showed the weight increase in HFR arose from an increase in percent fat consumed. We conclude that reducing the number of kilocalories consumed from a high-fat diet attenuates but does not prevent the development of type 2 diabetes and obesity in the B6 mouse.

Carotenoids in health and disease: recent scientific evaluations, research recommendations and the consumer.

In addition to his many research achievements, James Allen Olson made important contributions to evaluations of the role of dietary carotenoids in prevention of chronic diseases such as cancer, heart disease and age-related macular degeneration in well-nourished populations. This paper reviews recent scientific evaluations of the role of carotenoids in disease, recommendations for future research, and consumer-related trends of relevance to carotenoids. Authoritative scientific evaluations by key leading thinkers have not been able to ascribe a disease prevention function to carotenoids because of the absence of definitive evidence. These leading thinkers recommend that future research on the role of carotenoids in disease focus on the complexities of diet, genetics and environment in the disease process. This research is important to make it possible for consumers to derive optimal health promoting benefits from fruits and vegetables in the context of changing dietary patterns.

Diet and lifestyle correlates of lutein in the blood and diet.

Observational studies have suggested an inverse relationship between dietary or serum lutein and risk for age-related macular degeneration and cataracts. This evidence has stimulated interest in the biological and other characteristics of lutein, and also zeaxanthin, a structurally similar carotenoid; together, they comprise the macular pigment. Accurate interpretation of data linking dietary intake or serum concentrations of lutein and zeaxanthin and risk for eye disease in epidemiologic and clinical studies requires knowledge of biological and nondietary factors influencing these intake data or concentrations. The primary aims of this study were to identify the correlates of dietary lutein + zeaxanthin intake and the determinants of serum lutein and zeaxanthin concentrations in a heterogeneous community-based sample of adults aged 18-92 y, recruited and examined at three U.S. sites (n = 2786). An additional aim was to identify the determinants of change in serum lutein concentration from baseline to 1 y in a subset of 1368 study participants followed prospectively. Demographic characteristics (age, sex, race/ethnicity, education), body mass index and lifestyle factors (exercise, sun exposure, smoking, alcohol consumption) were significantly (P < 0.05) associated with dietary lutein + zeaxanthin intake. Demographic characteristics, dietary intake, serum cholesterol concentration, body mass index and smoking explained 24% of the variance in serum lutein concentration. Race/ethnicity, education level and smoking had the strongest associations with serum lutein concentration. Every 10% increase in dietary lutein + zeaxanthin intake was associated with a 2.4% increase in serum lutein concentration. Notably, however, the amount of variance in serum concentration that is explained by demographic characteristics, health-related behaviors and lifestyle factors remains substantial.