Carotenoid study results

The absorption and transport processes of many of the phytochemicals present in food are complex and not fully understood, and prediction of their bioavailability is problematic. This is particularly true of the lipid-soluble phytochemicals. In this chapter the measurement of carotenoid bioavailability will be discussed. The carotenoids serve as an excellent example of where too little understanding of food structure, the complexity of their behaviour in foods and human tissues, and the nature and cause of widely different individual response to similar intakes, can lead to misinterpretation of study results and confusion in our understanding of the relevance of these (and other) compounds to human health. 

A large set of results obtained in recent years for various carotenoids (see, e.g., Simonyi et al. (2003) for review) suggests that planarity of the carotenoid molecule is crucial for aggregation. This hypothesis is supported by the observation that zeaxanthin and astaxanthin, both fairly planar molecules, form aggregates more readily than other carotenoids. Moreover, zeaxanthin and astaxanthin are the only two carotenoids studied so far that can, depending on preparation conditions, form exclusively either H- or J-aggregates (Billsten et al. 2005, Kopsel et al. 2005, Avital... 

Pathways. Studies of carotenoid transformations that take place when a mutant strain, PGl, of the green alga Scenedesmus obliquus is transferred from dark to light conditions have indicated that the transformations 15-cw-phytoene (180) 15-c/5-phytofluene (181) - 15-cis- -carotene (182) -> trans-C-caro-tene (183) (Scheme 7) take place in the biosynthesis of the normal cyclic carotenoids. The results were also in agreement with the formation of the xanthophylls lutein (16) and zeaxanthin (174) from the corresponding carotenes. 

Several studies have investigated the role of dietary factors in prostate cancer risk, but results appear inconsistent. Significant effects have not been detected for dietary soya products certain vegetables, beans, fruit, rice and seaweed appear to be protective in some studies, while another has shown no protective effect from seaweed or vegetable consumption. In addition, a number of other risk factors have been shown to be associated with an increased risk of this cancer, including meat and dairy products and carotenoids. 

The antioxidant activities of carotenoids and other phytochemicals in the human body can be measured, or at least estimated, by a variety of techniques, in vitro, in vivo or ex vivo (Krinsky, 2001). Many studies describe the use of ex vivo methods to measure the oxidisability of low-density lipoprotein (LDL) particles after dietary intervention with carotene-rich foods. However, the difficulty with this approach is that complex plant foods usually also contain other carotenoids, ascorbate, flavonoids, and other compounds that have antioxidant activity, and it is difficult to attribute the results to any particular class of compounds. One study, in which subjects were given additional fruits and vegetables, demonstrated an increase in the resistance of LDL to oxidation (Hininger et al., 1997), but two other showed no effect (Chopra et al, 1996 van het Hof et al., 1999). These differing outcomes may have been due to systematic differences in the experimental protocols or in the populations studied (Krinsky, 2001), but the results do indicate the complexity of the problem, and the hazards of generalising too readily about the putative benefits of dietary antioxidants. 

The relationship between serum and tissue concentrations of lutein and zeaxanthin was recently studied by Johnson et al, (2000). Dietary intake of xanthophyll-rich vegetables (for example, spinach and com) resulted in significant increases in lutein concentration in serum, adipose tissue and buccal cells, and this correlated with changes in MP density. However, P-carotene and lycopene are normally the major carotenoids detected in buccal cells (Peng et al, 1994). 

Carotenoids and breast cancer — Among seven case-control studies investigating the correlation between different carotenoid plasma levels or dietary intakes and breast cancer risk, five showed significant inverse associations with some carotenoids. - In most cases, this protective effect was due to 3-carotene and lutein. However, one (the Canadian National Breast Screening Study ) showed no association for all studied carotenoids including (I-carotene and lutein. More recently, another study even demonstrated a positive correlation between breast cancer risk and tissue and serum levels of P-carotenes and total carotenes. Nevertheless, these observational results must be confirmed by intervention studies to prove consistent. 

Dorgan, J.F. et al.. Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk results from a prospective study in Columbia, Missouri (United States), Cancer Causes Control, 9, 89, 1998. 

Botterweck, A. A. et al., Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma results from a prospective study after 6.3 years of foUow-up, Cancer, 88, 131, 2000. 

Zeegers, M.P. et al.. Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk Results from the Netherlands Cohort Study, Br. J. Cancer, 85, 977, 2001. 

Both intact carotenoids and their apolar metabolites (retinyl esters) are secreted into the lymphatic system associated with CMs. In the blood circulation, CM particles undergo lipolysis, catalyzed by a lipoprotein lipase, resulting in the formation of CM remnants that are quickly taken up by the liver. In the liver, the remnant-associated carotenoid can be either (1) metabolized into vitamin A and other metabolites, (2) stored, (3) secreted with the bile, or (4) repackaged and released with VLDL particles. In the bloodstream, VLDLs are transformed to LDLs, and then HDLs by delipidation and the carotenoids associated with the lipoprotein particles are finally distributed to extrahepatic tissues (Figure 3.2.2). Time-course studies focusing on carotenoid appearances in different lipoprotein fractions after ingestion showed that CM carotenoid levels peak early (4 to 8 hr) whereas LDL and HDL carotenoid levels reach peaks later (16 to 24 hr). 

Results obtained in in vivo and ex vivo experiments are of various types. Some studies have found positive effects of the consumption of carotenoids or foods containing carotenoids on the markers of in vivo oxidative stress, even in smokers. Other studies demonstrated no effects of carotenoid ingestion on oxidative stress biomarkers of lipid peroxidation. " It should be noted that for studies using food, the activity observed may also be partly due to other antioxidant molecules in the food (phenols, antioxidant vitamins) or to the combination of actions of all the antioxidants in the food. 

Extensive studies in vitro from many groups have confirmed that exposure of LDL to a variety of pro-oxidant systems, both cell-free and cell-mediated, results in the formation of lipid hydroperoxides and peroxidation products, fragmentation of apoprotein Bioo, hydrolysis of phospholipids, oxidation of cholesterol and cholesterylesters, formation of oxysterols, preceded by consumption of a-tocopherol and accompanied by consumption of 8-carotene, the minor carotenoids and 7-tocopherol. 

To validate the skin carotenoid RRS detection approach, we initially carried out an indirect validation experiment that compared HPLC derived carotenoid levels of fasting serum with RRS derived carotenoid levels for inner palm tissue sites. Measuring a large group of 104 healthy male and female human volunteers, we obtained a significant correlation (p < 0.001) with a correlation coefficient of 0.78 (Smidt et al. 2004). Recently, we carried out a direct validation study, in which we compared in vivo RRS carotenoid skin responses with HPLC-derived results, using the thick... 

The interaction of carotenoids with cigarette smoke has become a subject of interest since the results of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group 1994 (ATBC) and CARET (Omenn et al. 1996) studies were released. P-Carotene has been hypothesized to promote lung carcinogenesis by acting as a prooxidant in the smoke-exposed lung. Thus, the autoxidation of P-carotene in the presence of cigarette smoke was studied in model systems (toluene) (Baker et al. 1999). The major product was identified as 4-nitro-P-carotene, but apocarotenals and P-carotene epoxides were also encountered. 

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