Because of their antioxidant properties, carotenoids may have beneficial effects in preventing cancer and cardiovascular disease. However, in humans consuming carotenoid-rich vegetables, data concerning the antioxidant effects of carotenoids are rather scarce. A human intervention trial was conducted, therefore, to determine whether a moderately increased consumption of carotenoid-rich vegetables would influence the antioxidant status in 23 healthy men. This short-term feeding study lasted 8 wk during which the men consumed a low carotenoid diet. A 2-wk low carotenoid period was followed by daily consumption of 330 mL tomato juice, then by 330 mL carrot juice and then by 10 g of spinach powder, each for 2 wk. Antioxidant status [water-soluble antioxidants in serum, ferric reducing ability of plasma (FRAP) and antioxidant enzyme activities] and lipid peroxidation (plasma malondialdehyde and ex vivo oxidation of LDL) were determined. In a subgroup of 10 men, lipoprotein carotenoids were measured. The consumption of carotenoid-rich vegetables significantly increased selected carotenoids in lipoproteins but had only minor effects on their relative distribution pattern. Tomato juice consumption reduced plasma thiobarbituric acid reactive substances (TBARS) by 12% (P Ͻ 0.05) and lipoprotein oxidizability in terms of an increased lag time (18%, P Ͻ 0.05). Carrot juice and spinach powder had no effect on lipid peroxidation. Water-soluble antioxidants, FRAP, glutathione peroxidase and reductase activities did not change during any study period. In evaluating the low carotenoid diet, we conclude that the additional consumption of carotenoid-rich vegetable products enhanced lipoprotein carotenoid concentrations, but only tomato juice reduced LDL oxidation in healthy men.

A combination of dietary and host-related factors determines iron and zinc absorption, and several in vitro methods have been developed as preliminary screening tools for assessing bioavailability. An expert committee has reviewed evidence for their usefulness and reached a consensus. Dialyzability (with and without simulated digestion) gives some useful information but cannot predict the correct magnitude of response and may sometimes predict the wrong direction of response. Caco-2 cell systems (with and without simulated digestion) have been developed for iron availability, but the magnitude of different effects does not always agree with results obtained in human volunteers, and the data for zinc are too limited to draw conclusions about the validity of the method. Caco-2 methodologies vary significantly between laboratories and require experienced technicians and good quality cell culture facilities to obtain reproducible results. Algorithms can provide semi-quantitative information enabling diets to be classified as high, moderate, or low bioavailability. While in vitro methods can be used to generate ideas and develop hypotheses, they cannot be used alone for important decisions concerning food fortification policy, selection of varieties for plant breeding programs, or for new product development in the food industry. Ultimately human studies are required for such determinations.

Several in vitro assays have been developed to evaluate the gastrointestinal absorption of compounds. Our aim was to compare 3 of these methods: 1) the bio-mimetic artificial membrane permeability assay (BAMPA) method, which offers a highthroughput, noncellular approach to the measurement of passive transport; 2) the traditional Caco-2 cell assay, the use of which as a high-throughput tool is limited by the long cell differentiation time (21 days); and 3) The BioCoat™ high-throughput screening Caco-2 Assay System, which reduces Caco-2 cell differentiation to 3 days. The transport of known compounds (such as cephalexin, propranolol, or chlorothiazide) was studied at pH 7.4 and 6.5 in BAMPA and both Caco-2 cell models. Permeability data obtained was correlated to known values of human absorption. Best correlations (r = 0.9) were obtained at pH 6.5 for BAMPA and at pH 7.4 for the Caco-2 cells grown for 21 days. The Caco-2 BioCoat™ HTS Caco-2 Assay System does not seem to be adequate for the prediction of absorption. The overall results indicate that BAMPA and the 21-day Caco-2 system can be complementary for an accurate prediction of human intestinal absorption. (Journal of Biomolecular Screening 2004:598-606) Key words: BAMPA, bioavailability, Caco-2, permeability A LTHOUGH BIOLOGICAL EFFICACY is the key issue during the discovery process of active compounds, other factors such as bioavailability are equally important when the action of the ingredient is not limited to the gastrointestinal tract. An efficacious compound must be sufficiently bioavailable to perform its expected activity. The gastrointestinal absorption of an orally administered compound is one of the key factors for its bioavailability. Because absorption potential has become a more important criterion in the discovery process, there is a need for reliable screening methods to assess for compound permeability. 1Intestinal absorption screening assays should be highly predictive, fast, reliable, cost-effective, and require a small amount of compound. 2,3Current approaches include physicochemical models, in silico computational models, in vitro models (cell and tissue based), in situ models of intestinal perfusion, and in vivo animal models. 1The intestinal absorption of a compound depends on 2 major parameters: 1) permeability across the epithelial mucosa and 2) gastrointestinal transit. Because gastrointestinal transit can be evaluated only in vivo, all in vitro systems can determine only mucosal permeability.The main barrier for the absorption of a compound is formed by the intestinal epithelium, and several routes can be followed to cross this barrier. The passive transcellular pathway involves the movement of solute molecules across the apical membrane, through the cytoplasm, and across the basolateral membrane. This is the predominant route for hydrophobic compounds. Another passive route is via the tight junctions between the enterocytes: the paracellular pathway. Small hydrophilic compounds are mostly transported via the paracellular route...

Iron deficiency is the most common nutritional disorder worldwide. Iron fortification of foods is considered to be the most cost-effective long-term approach to reduce iron deficiency. However, for fortified foods to be effective in reducing iron deficiency, the added iron must be sufficiently bioavailable. In this study, fortification of whole-grain wheat flour with different sources of iron was evaluated in vitro by measuring the amount of dialyzable iron after simulated gastrointestinal digestion of flour baked into chapatis and subsequent intestinal absorption of the released iron using Caco-2 cell layers. The dialyzability of iron from iron-fortified wheat flour was extremely low. Additions of 50 mg/kg iron to the flour in the form of ferrous sulfate, Ferrochel amino acid chelate, ferric amino acid chelate taste free (TF), Lipofer, ferrous lactate, ferrous fumarate, ferric pyrophosphate, carbonyl iron, or electrolytic iron did not significantly increase the amount of in vitro dialyzable iron after simulated gastrointestinal digestion. In contrast, fortification of flour with SunActive Fe or NaFeEDTA resulted in a significant increase in the amount of in vitro dialyzable iron. Relative to iron from ferrous sulfate, iron from SunActive Fe and NaFeEDTA appeared to be 2 and 7 times more available in the in vitro assay, respectively. Caco-2 cell iron absorption from digested chapatis fortified with NaFeEDTA, but not from those fortified with SunActive Fe, was significantly higher than from digested chapatis fortified with ferrous sulfate. On the basis of these results it appears that fortification with NaFeEDTA may result in whole-grain wheat flour that effectively improves the iron status.

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