1131-labeled fats, absorption

The potential use of C-labelled compounds in clinical research has not yet been fully appreciated. There is an increasing demand for C-labelled amino acids to complement N studies of human nitrogen metabolism in addition to C fatty acids, which would permit the study of fatty acid and triglyceride metabolism to be extended to patients in whom the use of C analogues are ethically unacceptable. One of the few reports involving the use of C-labelled fatty acids employed palmitic and oleic acids to study fat absorption in a patient with chyluria [308]. These investigators fed (carhox y/- C)-labelled... 

The frequently met statement that the major portion of absorbed fat passes into the lymph stream stems from the classical experiments performed by Munk and Rosenstein in 1891 on a patient suffering from elephantiasis, in whom a lymphatic fistula developed in the left leg. From such a fistula, these workers were able to recover as much as 60% of the fat of an ingested meal. Ever since the appearance of this report, much time has been expended in a search for the path of absorption of the 40 % that was not recovered from lymph fistula. Recent work with labeled fats has shown, however, that this search was unnecessary, at least so far as long-chain fatty acids are concerned. 

Because Olestra is not digested, it behaves much like mineral oil. The laxative properties, which are widely discussed, appear on the label. Like other indigestible lipids, Olestra can dissolve fat-soluble vitamins and carotenoids, which makes them unavailable for absorption. 

A study with a dog exposed to an occluded dermal dose of TOCP labeled with radioactive phosphorus provides limited evidence that organophosphate esters in hydraulic fluids may be widely distributed after dermal absorption (Hodge and Sterner 1943). Similar widespread distribution of radioactivity among tissues was observed in male cats after dermal exposure to [uniformly labeled 14C-phenyl]TOCP (Nomeir and Abou-Donia 1986). Tissues and fluids with the highest concentrations of radioactivity in these studies included the bile, gall bladder, urinary bladder, liver, kidney, and fat, thus suggesting that TOCP and metabolites are somewhat preferentially distributed to these tissues. 

B14. Blomstrand, R., A study on the intestinal absorption of fat in normal adults and in non-tropieal sprue with carbon-labelled oleic acid and palmitic acid. Acta Med. Scand. 152, 129-138 (1955). 

In animals, as is the case with humans, absorption and bioavailability is influenced by age. Smith s result of Ca retention equivalence between CCM and CaCOa in older rats is different to how younger rodents responded (Smith et al., 1987). CCM in OJ was determined to be relatively better absorbed and retained than the Ca in 2% fat milk (mean SFM retention rates 51.1 1.7 vs 42.2 1.8% p <. 001), respectively. This result was reproduced when, based on extrinsic labeling, the Ca from CCM in both AJ and OJ was reported to be better absorbed in juvenile rats than was the Ca from milk (p <. 05) (Andon et al., 1996b). 

In 1995 the FDA approved saquinavir, the first protease inhibitor, for use in combination with other nucleoside analogue medications. In 1999 a soft gel capsule formulation of saquinavir with considerably improved absorption characteristics was developed. Ritonavir and indinavir have been approved for use alone or in combination with nucleoside analogue medications in people with advanced HIV disease. Nelfinavir is the first protease inhibitor labeled for use in children. Amprenavir is the newest of the protease inhibitors. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. The most disturbing adverse reactions to protease inhibitors consist of the lipodystrophy syndrome with severe hyperlipidemia and unpredictable fat redistributions over the body... 

After 20 years and more than 200 million in research and development, Proctor Gamble received permission from the FDA in 1996 to market its fat substitute Olestra in certain snack foods (e.g., potato chips, crackers, and cheese puffs). Olestra, technically a sucrose polyester, is not digestible, so it adds neither fat nor calories to food. However, Olestra can inhibit the absorption of certain fat-soluble vitamins and other nutrients. Therefore, all products containing Olestra must be labeled with the following information This product contains Olestra. Olestra inhibits the absorption of some vitamins and other nutrients. Vitamins A, D, E, and K have been added. Also, as a condition of approval, Proctor Gamble must monitor consumption and conduct studies on Olestra s long-term effects. 

The walnut oil used in our study contained 26 6 mg naturally occurring hydroxy fatty acids. After the meal, plasma concentration of these unlabeled hydroxy fatty acids increased by 100% (from 0.54 0.07 to 1.09 0.24 imol/L, P < 0.05). One should realize that the calculation of absorption of the [U- C]-labeled hydroxy- or epoxy-fatty acids is based on the assumption that hydroxy TG are metabolized, transported in chylomicrons, and incorporated into VLDL as any other long-chain fatty acid (37). This may not be true. Less oxidized linoleic acid was incorporated into chylomicrons in CaCo-2 epithelial cells in culture (40). Thus, we may have underestimated the extent of absorption. Nevertheless, an important conclusion is that the more fat that is oxidized, the less there is to be absorbed. 

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