Medium chain fatty acids, absorption

Lindmark T, Kimura Y, Artursson P (1998) Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J Pharmacol Exp Ther 284 362-369... 

Constantinides, P.P., et al., Water-in-oil microemulsions containing medium-chain fatty acids/salts formulation and intestinal absorption enhancement evaludfibarm. Res., 13, 210, 1996. 

An important issue that has been recognized recently concerns the potential adverse effect of absorption enhancers on the rectal mucosa, as shown in rats after a single application [61,62], Safety evaluation of the applicability of absorption enhancers is imperative. In clinical application, medium-chain fatty acids such as sodium caprate are used only for suppositories containing antibiotics [36],... 

Lindmark, T., T. Nikkila, and P. Artursson. 1995. Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther 275 958. 

Van Hoogdalem, E.J., et al. 1988. Absorption enhancement of rectally infused cefoxitin sodium by medium-chain fatty acids in conscious rats Concentration-effect relationship. Pharm Res 5 453. 

Strategies to overcome the absorption barrier focus on the other hand on low molecular mass permeation enhancers (Chapter 5) such as medium chain fatty acids, which can still be regarded as a kind of gold standard. As low molecular mass permeation enhancers are per se rapidly uptaken from the gastrointestinal mucosa, however, the macromolecular drug is to a considerable high extent left alone behind in the gastrointestinal tract. In addition, local and systemic toxic side effects of low molecular mass permeation enhancers cannot be excluded. In contrast, polymeric permeation enhancers (Chapter 6) are simply too big to be absorbed from the GI tract. Consequently, systemic toxic side effects can be excluded. More recently various excipients could be identified as potent efflux pump inhibitors which can be subdivided into low molecular mass efflux pump inhibitors and polymeric efflux pump inhibitors (Chapter 7). Certain polymeric... 

Constantinides, P. P, Welzel, G., Ellens, H., Smith, P. L., Sturgis, S., Yiv, S. H., et al. (1996), Water-in-oil microemulsions containing medium-chain fatty acids/salts Formulation and intestinal absorption enhancement evaluation, Pharm. Res., 13(2), 210-215. 

In neonate, suckling mammals, short- and medium-chain fatty acids are preferentially split at the sn-3 triacylglycerol position by oral and gastric lipases and are absorbed in the stomach, while the long-chain fatty acids are hydrolyzed at the sn- and sn-2 positions and by pancreatic lipases and are absorbed in the small intestine (50, 51). With growth, the neonate fat digestion system becomes less active, and is replaced by the small intestine-pancreatic lipase pathway. But residual oral and gastric lipase activities and direct absorption of short-chain fatty acids in the... 

The presence of medium chain fatty acids and glycerides in food products has stimulated interest in their potential utility as absorption enhancers. Some fatty acids and glycerides have been shown to increase drug absorption under a variety of conditions, almost always in animals and in most cases after rectal dosing. However, some studies have yielded positive results after oral dosing. Oral insulin bioavailability was increased to 9-13% relative to IM administration by a mixture of sodium dodecanoate and cetyl alcohol. Aftiraxone absorption was enhanced by glyceryl-1-monooctanoate after oral, duodenal, and rectal administration to animals. 

The small intestinal tract is the major place of digestion and absorption. Protein digestion reaches approximately 15% in the stomach, and in the lower intestine, the hydrolyzed fraction amounts to about 60%. Seventy percent of fats, 60% of carbohydrates, and about 30% of protein and peptide are absorbed within the duodenum. Within enterocytes, triglycerides are resynthesized from long-chain fatty acids and transformed into chylomicrons, which are transported via the lymphatic system, whereas short- and medium-chain fatty acids are directly transported into mesenteric and portal vein system. 

Digestion and absorption of triacylglycerols with medium-chain fatty acids 12 carbons) proceed by a different pathway. Medium-chain triacylglycerols are partly water-soluble, are rapidly hydrolyzed by lingual and pancreatic lipases, and do not require the participation of bile acids. Some are absorbed intact and hydrolyzed inside the absorptive cell. Medium-chain fatty acids enter the portal... 

Short- and medium-chain fatty acids (C4 to C12) do not reqnire bile salts for their absorption. They are absorbed directly into intestinal epithelial cells. Because they do not need to be packaged to increase their solnbility, they enter the portal blood (rather than the lymph) and are transported to the liver bonnd to serum albumin. 

Ikeda, I., Tomari, Y., Sugano, M., Watanabe, S., and Nagata, J. 1991. Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid, and their effect on cholesterol absorption in rats. Lipids 26 369-373. 

Normally, absorbed lipids leave the mucosal cells in the form of chylomicrons which are discharged into the lymphatic system. Only short and medium chain fatty acids (up to Ciq) are carried by portal vein blood (Isselbacher 1964). In a-/3-lipoproteinemia no fat is seen in the lymphatic spaces of the small bowel (Isselbacher 1965), and no chylomicrons appear in the plasma after fat loading (see figure 5). It appears that the defect in a-jS-lipoproteinemia concerns the lipid transport from the mucosal cells into the lymphatic system. For the formation of chylomicrons, jS-lipoproteins (Isselbacher 1965), but not a-lipoproteins (Fredrickson 1966) seem to be necessary. The fat absorption defect is not improved with transfusion of normal jS-lipoproteins (Frezal et al. 1961). 

Isselbacher (1965) was able to show that the absorption of short and medium chain fatty acids is not impaired in a-j8-lipoproteinemia, and that, on a diet rich in such fatty acids, there is a significant decrease of the mucosal fat content. 

Jeppesen, RB. and Mortensen, RB. The influence of apreserved colon on the absorption of medium chain fatty acids in patients with small bowel resection. Gut 43,... 

Carvajal, O., Sakono, M., Sonoki, H., Nakayams, M., Kishi, T., Sato, M., Ikeda, I., Sugano, M., and Imaizumi, K. Structured triacylglycerol containing medium-chain fatty acids in sn 1(3) facilitates the absorption of dietary long-chain fatty acids in rats. Biosci. Biotechnol. Biochem. 64, 793-798, 2000. 

A study involving two types of stmctured lipids (randomized v.s. specific product) revealed that the fatty acids located in the sn-2 position of TAG are preferentially absorbed (10). The randomized stmctured lipid used contained EPA, DHA and capric acid randomly distributed in the molecule. The specific stmctured lipid had EPA and DHA at the sn-2 position and capric acid at the sn-1 and snA positions of TAG. The concentrations of EPA and DHA in lyn5)hatics were higher in the specific stmctured lipid than in the randomized stmctured lipid. Rapid hydrolysis and absorption of stmctured lipids containing medium-chain fatty acids at the snA and snA positions and long-chain fatty acids at the sn-2 position have also been reported (II). 

Medium-chain fatty acids also improve the absorption of many other nutrients. The absorption of minerals (particularly calcium and magnesium), B vitamins, fat soluble vitamins (A, D, E, K and beta-carotene) and also amino acids has been foimd to increase when infants are fed a diet containing MCFA. In addition, coconut oil can be digested by the salivary lipase, getting absorbed very fast to give energy like carbohydrates. All other fats need the pancreatic lipase for digestion that the infants do not have (Murthi et al., 1987). 

Another chemical property of the MCT, water solubility, makes the MCT colon absorption possible, a very important process for the CD patients. Medium chain fatty acids are also energy sources for the patients which suffer from ulceration and inflammation in the intestine (Andoh et al., 2000). The nutrition plays an important role in the management of patients with IBD. It seems that a dose of MCT oil up to 50 g/day can be a good dose for patients with ileitis or an extensive resection of the small intestine, as osmotic diarrhea (Eiden, 2003). 

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