Vitamin lymphatic transport

Intestinal lymphatic transport has also been shown to substantially contribute to the absorption of fat-soluble vitamins [91], ontazolast [26], probucol [16] and others. 

With exceptions, including halofantrine, DDT, and the lipophilic vitamins, the extent of lymphatic transport (as a proportion of the dose) is generally low. However, the compounds described in Table 5 are hydrophobic (as evidenced by the high log Ps), and their bioavailability is often low. Therefore, although the absolute extent of lymphatic transport may be low, the lymphatic contribution to the small fraction that is absorbed may be high, and alterations in the extent of lymphatic transport may have a significant effect on the extent of oral bioavailability. 

Malabsorption is defined as an inadequate assimilation of dietary substances due to defects in digestion, absorption or transport. Malabsorption can affect macronutrients (proteins, carbohydrates, fats), micronutrients (vitamins, minerals) or both, causing excessive faecal excretion and producing nutritional deficiencies and GI symptoms. Digestion and absorption occur in three phases, namely (i) the intra-lumen hydrolysis of fats, proteins and carbohydrates by enzymes, and emulsification by bile salts, (ii) digestion by brush-border enzymes and uptake of end-products and (iii) lymphatic transport of nutrients. Malabsorption can occur when any of these phases is impaired. 

Lymphatic uptake of the lipid soluble dye Sudan blue and Vitamin A acetate from triolein-in-water emulsions requires the presence of both bile salts and phosphatidylcholine [237]. However, the overall contribution of lymphatic uptake for these two solutes is very small. In the absence of sodium taurocholate in rats with bile hstulae the administration of 20 ml polysorbate 80 did not stimulate lymphatic transport, although absorption from a 4 % polysorbate 80 solution is equivalent to that for the triolein emulsions in intact amounts, but slightly more rapid. 

R. Blomhoff P. Helgerud, S. Dueland, T. Berg, J. I. Pederson, K. R. Norum, and C. A. Drevon, Lymphatic absorption and transport of retinol and vitamin D-3 from rat intestine—evidence for different pathways, Biochim. Biophys. Acta. 772 109-116 (1984). 

Critical to vitamin D3 action is its further metabolic conversion to more active compounds (Figure 1.3). Via its transport by DBP, vitamin D3 accumulates in the liver [48]. In rats, as much as 60-80% of an injected or oral dose of vitamin D3 locates to the liver [49-51], Intestinal absorption of vitamin D3 is in association with the chylomicron fraction via the lymphatic system. Vitamin D3 is delivered to the liver in blood from the thoracic duct only a few hours post ingestion [44], A specific portion of hepatic vitamin D3 in the rat is converted to 25-OH-D3 by a 25-hydroxylase system in the endoplasmic reticulum of hepatocytes [52, 53]. This enzyme (Km 10"8 M) is regulated to an extent by 25-OH-D3 and its metabolites. Higher concentrations of vitamin D3 are handled by a second 25-hydroxylase located in liver mitochondria [54], This enzyme, also known as CYP27, 27-hydroxylates cholesterol and thus appears less discriminating than the microsomal 25-OHase which does not use cholesterol as substrate [55, 56]. In humans, however,... 

Sterile parenteral oil-in-water emulsions have been used extensively for over 40 years for the intravenous administration of fats, carbohydrates, and vitamins to debilitated patients. Several vegetable oil-in-water emulsions are now available commercially with droplet sizes similar to that of chylomicrons (approximately 0.5-2 pm), the natural fat droplets in the blood that transport ingested fats to the lymphatic and circulatory systems (Table 1). More recently, such emulsions have been employed as intravenous carriers for poorly water-soluble lipophilic drugs such as vitamin K (e.g.. Sterile Phytonadione Injection U.S.P.) diazepam... 

Preformed vitamin A, most often in the form of retinyi ester, or carotenoids are subject to emulsification and mised micelle formation by the action of bile salts before being transported into the intestinal cell. Here the retinyi esters are moved across the mucosal membrane and hydrolyzed to retinol within the cell to then be reesterified by cellular retinol-binding protein II and packaged into chylomicra, which then enter the mesenteric lymphatic system and pass mto the systemic circulation. A small amount of the ingested retinoid is also converted into retinoic acid in the intestinal cell. The efficiency of absorption of preformed vitamin A is high at between 70% and 90%. ... 

The absorption of natural vitamin K from-the small intestine into the lymphatic system is facilitated by bile, as is true for other fat-soluble materials. Efibciency of absorption varies from 15% to 65% as reflected by recovery in lymph within 24 hours. Vitamins Ki and K2 are bound to chylomicrons for transport from mucosal cells to the liver. Menadione (Ks) is more rapidly and completely absorbed from the gut before entering the portal blood. In liver, intraceUular distribution is mostly in the microsomal fraction, where phenylation of menadione to form K2 occurs. Release of vitamin K to the blood stream allows association with circulating P-lipoproteins for transport to other tissue. Significant levels of vitamin K have been noted in the spleen and skeletal muscle. 

There is no doubt that in the absence of luminal bile salts there is diminished transport of long-chain fatty acids in intestinal lymph and there is evidence that a greater proportion of absorbed long-chain fatty acid is transported in portal venous blood [81,82]. Such observations have been interpreted to show diminished fatty acid esterification by the enterocyte. A similar re-routing of absorbed vitamin A in the bile-diverted animal from the lymphatic to the portal venous route has also been ascribed to defective esterification [83]. 

ABSORPTION, FATE, AND EXCRETION Both vitamins and are absorbed from the small intestine and transported as chylomicrons in the lymphatics. Bile salts are essential for adequate absorption. The primary route of vitamin D excretion also is the bile. Severe shortening or inflammation of the small bowel or hepatic or bihary dysfunction may cause overt vitamin D deficiency. 

Vitamin A in foods is present in its ester form and, after enzyme-catalyzed hydrolysis, it is absorbed into the gastrointestinal tract. After forming an emulsion in the presence of bile salts and pancreatic juices, it is incorporated into molecules of chylomicrons (Olson, 1996). Other forms of carotenoids are oxidatively converted to retinal in the intestinal mucosa. Then, via lymphatic vessels, it is transported from the bloodstream to the liver (Cortner et al., 1987). Vitamin A is primarily stored in the liver, and is also found in ester form in lipocytes. Transport from the liver depends on the level of retinol binding proteins (RBP) (Wolf and Phil, 1991). Vitamin A is well absorbed... 

The rate of vitamin K absorption in humans depends on the kind of fats included in the diet. Long-chain unsaturated fatty acids facilitate absorption of vitamin Kj in lymphatic vessels. The efficiency of this process is affected by the presence of bile salt and pancreatic juices, the form of vitamin K, as well as the site in the gastrointestinal tract. Vitamin Kj is primarily absorbed in the jejunum and ileum only small amounts are absorbed in the colon. From the lymphatic system, vitamin K is transported to the circulatory system and, in chylomicrons, to the liver from which it is distributed to target tissues. 

Dietary and endogenous fats are carried to the target organs by different lipoproteins, i.e. chylomicrons, LDL and HDL. These particles contain a core of TAG liposoluble vitamins and cholesteryl esters, surrounded by a phospholipid and free cholesterol layer. These also contain, by the way, specific proteins, called apolipoproteins (apo) which act as enzyme cofactors or receptor ligands. Exogenous fat is transported in chylomicrons from the intestinal epithelium to the peripheral cells, reaching the bloodstream via flie lymphatic system [11],... 

Retinol is nearly always present in the food in the form of esters which are hydrolysed in the lumen of the intestine. The retinol released is quite readily absorbed into the mucosal cells where it is re-esterified, chiefly with palmitic acid. The retinyl esters are then transported via the lymphatic system into the portal circulation from which they are removed and stored in the liver. Release of the vitamin from the liver depends on the production by the liver of a special retinolbinding protein (RBP). Production of the retinol-binding protein may be disturbed in diseases of the liver or kidneys or in protein/energy malnutrition. In such circumstances retinol cannot be mobilized from the stores and a secondary deficiency may result. Thus it can be seen that the level of retinol in the general circulation is normally highly regulated and is more or less independent of the body s reserves. 

Cholecalciferol, ergocalciferol and metabolites of these vitamins ingested via foods are resorbed in the intestines and, bound to DBP, are transported to the liver by the lymphatic vascular system, where they are stored or metabolised. 

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