Carotenoid plasma concentrations

It is well known that excessive intake of P-carotene may lead to carotenodermia (yellow skin), and it is undoubtedly the case that some carotenoid is directly lost via the skin or through photo-oxidation in the skin. As far as is known the carotenoids are not cytotoxic or genotoxic even at concentrations up to 10 times the normal plasma concentration which may cause carotenodermia. However, they are associated with amenorrhoea in girls who may be consuming bizarre diets and, in long-term supplementation studies, with an increase in lung cancer (The Alpha-tocopherol, Beta-carotene Cancer Prevention Study Group, 1994). 

The measurement of carotenoid absorption is fraught with difficulties and riddled with assumptions, and it is therefore a complex matter. Methods may rely on plasma concentration changes provoked by acute or chronic doses, oral-faecal mass balance method variants and compartmental modelling. 

Health benefits of carotenoids are related to their bioavailability and thus then-absorption. Plasma concentration is considered a good biomarker of fruit and vegetable consumption. Table 3.1.1 shows plasma carotenoid levels in EPIC study subjects from 16 European locations. EPIC was the first large cross-sectional study analyzing plasma carotenoid levels in several European populations. ... 

Potischman, N. et al.. Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A, Am. J. Clin. Nutr, 52, 909, 1990. 

Azeredo, V. B. and N. M. Trugo (2008). Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations. Nutrition 24(2) 133-139. 

Caroteneinplasma is mainly inlipoproteins thus, as with vitamin E (Section 4.5), measurements of plasma concentrations of carotene should be related to either cholesterol or total plasma lipids. Only 10% to 20% of total plasma carotenoids is /S -carotene, with a very wide range of individual variation. There are no reliable determinations of /S - carotene or total provitamin A carotenoids... 

Decreased carotenoid concentrations are associated with increased risk of stroke (Leppala et al., 1999) and vitamin A levels are decreased in stroke patients (Cherubini et al., 2000). Plasma concentrations of alpha- and beta-carotene are lower in patients with acute ischemic stroke than in healthy controls and are negatively correlated with neurological deficits in stroke patients (Chang et al., 2005). 

A concern has been raised that phytosterol doses that are effective for cholesterol reduction may impair the absorption and lower blood concentrations of fat-soluble vitamins and antioxidants. A number of studies showed that phytosterols had no effect on plasma concentrations of vitamin D, retinol, or plasma-lipid-standardized alpha-tocopherol. Moreover, the reports of the effect of phytosterols on concentrations of blood carotenoids (lutein, lycopene, and alpha-carotene) are controversial. There seems to be general agreement that phytosterol doses >1 g/d significantly decrease LDL-C standardized beta-carotene concentrations however, it remains to be determined whether a reported 15-20% reduction in beta-carotene due to phytosterol supplementation is associated with adverse health effects. Noakes et al. found that consumption of one or more carotenoid-rich vegetable or fruit servings a day was sufficient to prevent lowering of plasma carotenoid concentrations in 46 subjects with hypercholesterolemia treated with 2.3 g of either sterol or stanol esters. 

If the prevention of oxidative DNA damage plays an important role in the cancer chemopreventive effects of dietary antioxidants, then one would expect to see an inverse relationship between antioxidant intake and biomarkers of oxidative DNA damage. Lymphocyte ascorbate concentrations were inversely associated with lymphocyte 8-oxodG concentrations in 105 men and women (r=-0.28)." However, plasma concentrations of a-tocopherol and carotenoids were positively correlated with lymphocyte concentrations of 8-oxodG in a study of 52 healthy women (r=0.29 to... 

Schneeman, B.O. 1998. Dietary fiber and gastrointestinal function. Nutr. Res. 18, 632-652. Schweigert, F.J., Klingner, J., Hurtienne, A., and Zunfl, H.J. 2003. Vitamin A, carotenoid and vitamin E plasma concentrations in children fi om l os in relation to sex and growth failure. Nutr. J. 2, 17 available from http //www.nutritionj.eom/content/2/l/17). 

Mathews-Roth, M.M., Plasma concentration of carotenoids after large doses of beta-carotene. Am. J. Clin. Nutr., 52, 500, 1990. 

Case-control studies measuring plasma concentrations of antioxidants concluded that high levels of carotenoids or vitamin C are consistent with reduced risk (Jacques et al., 1988 Mohan et al., 1989). Robertson et al. (1989) showed that regular use of vitamin C or vitamin E supplements reduces the risk of cataract surgery by 50 to 60%. 

The daily requirement of vitamin A (Table 6.3) is provided to an extent of 75% by retinol intake (as fatty acid esters, primarily retinyl palmitate), while the remaining 25% is through P-carotene and other provitaminactive carotenoids. Due to the limited extent of carotenoid cleavage, at least 6 g of P-carotene are required to yield 1 g retinol. Vitamin A absorption and its storage in the fiver occur essentially in the form of fatty acid esters. Its content in fiver is 250pg/g fresh tissue, i.e. a total of about 240-540 mg is stored. The fiver supplies the blood with free retinol, which then binds to proteins in blood. The plasma concentration of retinol averages 1.78 pmol/1 in women and 2.04 lamol/l in men. 

When the concentration of a solution of a given retinoid or carotenoid is known, the best way to express the value is by using molar units, e.g. a plasma concentration of 2 pmol/1 is equivalent to 57.2 pg/dl. In such chemical calculations, molecular weights are used 286 g/mol for vitamin A and 537 g/mole for P-carotene. 

Carotenoid and tocopherol concentrations in plasma, peripheral blood mononuclear cells and red blood cells after long-term beta-carotene supplementation in men. Am J Clin Nutr 63(4) 553-8. 

Among 27 prospective and case-control studies, 16 reported inverse associations between some carotenoids and CVDs, taking plasma or serum concentration as carotenoid biomarkers (11 of 16 studies), dietary intake (5 of 16 studies), or adipose tissue level (1 of 16 studies). With regard to the findings from the studies based on CVD risk, only two of seven presented significant inverse associations of carotenoids, particularly lycopene and P-carotene, whereas five studies of nine showed inverse correlations between myocardial infarcts and lycopene and/or P-carotene the others presented no associations. ... 

The lag-phase measurement at 234 nm of the development of conjugated dienes on copper-stimulated LDL oxidation is used to define the oxidation resistance of different LDL samples (Esterbauer et al., 1992). During the lag phase, the antioxidants in LDL (vitamin E, carotenoids, ubiquinol-10) are consumed in a distinct sequence with a-tocopherol as the first followed by 7-tocopherol, thereafter the carotenoids cryptoxanthin, lycopene and finally /3-carotene. a-Tocopherol is the most prominent antioxidant of LDL (6.4 1.8 mol/mol LDL), whereas the concentration of the others 7-tocopherol, /3-carotene, lycopene, cryptoxanthin, zea-xanthin, lutein and phytofluene is only 1/10 to 1/300 of a-tocopherol. Since the tocopherols reside in the outer layer of the LDL molecule, protecting the monolayer of phospholipids and the carotenoids are in the inner core protecting the cholesterylesters, and the progression of oxidation is likely to occur from the aqueous interface inwards, it seems reasonable to assign to a-tocopherol the rank of the front-line antioxidant. In vivo, the LDL will also interact with the plasma water-soluble antioxidants in the circulation, not in the artery wall, as mentioned above. 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

Carotenoids are also present in animals, including humans, where they are selectively absorbed from diet (Furr and Clark 1997). Because of their hydrophobic nature, carotenoids are located either in the lipid bilayer portion of membranes or form complexes with specific proteins, usually associated with membranes. In animals and humans, dietary carotenoids are transported in blood plasma as complexes with lipoproteins (Krinsky et al. 1958, Tso 1981) and accumulate in various organs and tissues (Parker 1989, Kaplan et al. 1990, Tanumihardjo et al. 1990, Schmitz et al. 1991, Khachik et al. 1998, Hata et al. 2000). The highest concentration of carotenoids can be found in the eye retina of primates. In the retina of the human eye, where two dipolar carotenoids, lutein and zeaxan-thin, selectively accumulate from blood plasma, this concentration can reach as high as 0.1-1.0mM (Snodderly et al. 1984, Landrum et al. 1999). It has been shown that in the retina, carotenoids are associated with lipid bilayer membranes (Sommerburg et al. 1999, Rapp et al. 2000) although, some macular carotenoids may be connected to specific membrane-bound proteins (Bernstein et al. 1997, Bhosale et al. 2004). 

Breastfed infants are exclusively dependent on the lutein and zeaxanthin content of mother s milk because lutein and zeaxanthin cannot be biosynthesized by the human body as mentioned earlier. In comparison to other carotenoids present in mother s milk, lutein and zeaxanthin were reported to constitute the highest relative amount (Khachik et al. 1997b, Azeredo and Trugo 2008). Their concentrations in mother s milk approximately reflect maternal intake levels of these carotenoids (Canfield et al. 2003, Jackson and Zimmer 2007). Currently, most commercially available infant formulas either do not contain lutein and zeaxanthin at all or only in trace amounts. In this context, an earlier publication (Johnson and Norkus 1995) documented decreasing lutein and zeaxanthin plasma levels in infants who were formula-fed for 1 month after birth. 

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