Liver vitamin A and

T.W. Knight and A.F. Death, Effects of oral and injected vitamin A (retinol) supplements on liver vitamin A and plasma carotenoid and cholesterol concentrations in cattle. Animal Sci. 69 (1999) 607-612. 

The amounts of most nutrients, especially vitamins, needed to both prevent and treat deficiency diseases are small. The average intake of Img of vitamin Bi is sufficient to prevent a deficiency disease of that vitamin, while lOmg of B could cure an advanced case of someone about to die of beriberi. Although small doses of vitamins cure deficiencies, large doses of some vitamins such as A and D can be harmful since these two vitamins are already stored by the liver. Vitamins A and D are fat soluble vitamins and can accumulate to the point of becoming toxic. Most other vitamins are water soluble and are excreted in the urine throughout the day. 

To look at the determinants of vitamin A disposal rate, we used multiple regression analysis to relate our data on disposal rate for 62 rats to vitamin A intake, liver vitamin A levels, and plasma retinol pool size (Fig. 10) (Kelley et al., 1994). These three variables predict 91% of the variation in disposal rate 68% of the reduction in sum of squares comes from plasma retinol, 18% from liver vitamin A, and 14% from vitamin A intake. Our data indicate that disposal rate does not fall until liver vitamin A levels are essentially depleted. That is, as long as plasma retinol levels are normal, degradation rate is high, implying a nonfunctional utilization of the vitamin. We call this degradative preservation. We conclude that plasma retinol is the major determinant of vitamin A disposal rate and hypothesize that... 

Dugan, M.E.R., RoUand, D.C., Best, D.R., and Meadus, WJ. (2002) The Effects of Feeding Conjugated Linoleic Acid on Pig Liver Vitamin A and Retinol Binding Protein mRNA, Can. J. Anim. Sci. 82,461-463. 

Both intact carotenoids and their apolar metabolites (retinyl esters) are secreted into the lymphatic system associated with CMs. In the blood circulation, CM particles undergo lipolysis, catalyzed by a lipoprotein lipase, resulting in the formation of CM remnants that are quickly taken up by the liver. In the liver, the remnant-associated carotenoid can be either (1) metabolized into vitamin A and other metabolites, (2) stored, (3) secreted with the bile, or (4) repackaged and released with VLDL particles. In the bloodstream, VLDLs are transformed to LDLs, and then HDLs by delipidation and the carotenoids associated with the lipoprotein particles are finally distributed to extrahepatic tissues (Figure 3.2.2). Time-course studies focusing on carotenoid appearances in different lipoprotein fractions after ingestion showed that CM carotenoid levels peak early (4 to 8 hr) whereas LDL and HDL carotenoid levels reach peaks later (16 to 24 hr). 

Health benefits — Research reports indicate that natural (3-carotene possesses numerous benefits for the human body and consistently supports the use of (3-carotene as part of the human diet. The human body converts (3-carotene to vitamin A via body tissues as opposed to the liver, hence avoiding a build-up of toxins in the liver. Vitamin A is essential for the human body in that it assists the immune system and helps battle eye diseases such as cataracts and night blindness, various skin ailments such as acne, signs of aging, and various forms of cancer. 

Carotene (all-trans), (3-cryptoxanthin (all-trans and -cis), zeaxanthin (all-trans), luteoxanthin isomers, violaxanthin (all-trans and -cis), and neoxanthin (all-trans and -cis) were identified in several mango cultivars (Mercadante and others 1997 Ornelas-Paz and others 2007, 2008). Mango retinol was found to be highly bioavail-able by estimating vitamin A and carotene reserves in the liver and plasma of rats. Information on the tocopherol content in mango is very scarce, but it seems to be low (Burns and others 2003 Ornelas-Paz and others 2007). 

The key experiments leading to the identification of vitamin D were those of Mellanby (1918-1919) using puppies. When they were fed on bread, skimmed milk, linseed oil, yeast (to give B vitamins), and orange juice (vitamin C) the puppies developed rickets. When cod-liver oil and/or butter were added, rickets was prevented. The distinction between the effects of vitamin A and the anti-rachitic factor was aided by the sensitivity of vitamin A to oxidation. Aerated (oxidized) cod-liver oil no longer cured xerophthalmia but its anti-rachitic properties were unaffected (McCollum, 1922). 

In the Artie Eskimos depended historically on fish for their supply of vitamin D, whereas in the tropics a supply is unnecessary. Excessive intakes of vitamins A and D can be lethal. The liver is the storage organ for fat-soluble vitamins Eskimos avoided hypervitaminoses by discarding livers of polar bears which get a surfeit of vitamins A and D from their diet of seals and fish. 

Because 1,4-dichlorobenzene is a liver toxin, it probably can interact with other chemicals that are liver toxicants. These toxicants are many, and include ethanol, halogenated hydrocarbons (chloroform, carbon tetrachloride, etc ), benzene, and other haloalkanes and haloalkenes. In addition, 1,4-dichlorobenzene toxicity may also be exacerbated by concurrent exposure with acetaminophen, heavy metals (copper, iron, arsenic), aflatoxins, pyrrolizidine alkaloids (from some types of plants), high levels of vitamin A, and hepatitis viruses. Such interactions could either be additive or S5mergistic effects. 

It has been reported that toxins (BaP, TCDD) are able to disrupt the normal vitamin A metabolism and interact with vitamin A metabolizing enzymes (LRAT, REH) in different tissues (Hanberg et al, 1998 Nilsson et al, 2000). In limgs, intestine, adrenals, and liver, it has been well established that BaP and TCDD affect these tissue stores of vitamin A and cause decreased levels of vitamin A (Biesalski and Stofft, 1992 Nilsson et ah, 2000). 

Recently we published data that even in countries with excellent food sources and availability, insufficient vitamin A supply will occur (Schulz et ah, 2007). The aim of this trial was to analyze vitamin A and p-carotene status and investigate the contribution of nutrition to vitamin A and p-carotene supply in mother-infant pairs of multiparous births or births within short birth rates. Twenty-nine volimteers aged between 21 and 36 years were evaluated for 48 hours after delivery. In order to establish overall supply, retinol and p-carotene were determined in maternal plasma, cord blood, and colostrum via HPLC analysis. A food frequency protocol was obtained from all participants. Regardless of the high-to-moderate socioeconomic background, 27.6% of participants showed plasma retinol levels below 1.4 pmol/liter, which can be taken as borderline deficiency. In addition, 46.4% showed retinol intake <66% of RDA and 50.0% did not consume liver at all, although liver contributes as a main source for preformed retinol. Despite a high total carotenoid intake of 6.9 3.9mg/day, 20.7% of mothers showed plasma levels <0.5 pmol/liter p-carotene. 

Shensi, J. P., Chytil, F., and Stahlman, M. T. (1985). Liver vitamin A reserves of very low birth weight neonates. Pediatr. Res. 19,892-893. 

Mechanism of Action An antioxidant that prevents oxidation of vitamins A and C, protects fatty acids from aff ack by free radicals, and protects RBCs from hemolysis by oxidizing agents. Therapeutic Effect Prevents and treats vitamin E deficiency. Pharmacokinetics Variably absorbed from the GI tract (requires bile salts, dietary fat, and normal pancreatic function). Primarily concentrated in adipose tissue. Metabolized in the liver. Primarily eliminated by biliary system. 

Cod liver oil and shark liver oil Rich source of vitamin A and D. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

The liver of sharks and other oily fishes sometimes accumulate loxic levels of vitamin A, and cases of acme poisoning have been reported hoth among Eskimos and the Japanese. 

High vitamin A and procarotenoids content (20,000 76.000 IU./100 grams).1. Carrot, dandelion green, kohlrabi, liver (beef, calf, chicken, pig, sheep), liver oil (cod, halibut, salmon, shark, sperm whale), mint, palm oil, parsley, spinach, turnip greens. 

Medium vitamin A and procarotenoids content (1,000-10,000 I. U./100 grams). Apricot, beet greens, broccoli, butter, chard, cheese (except cottage), cherry (sour), chicory, chives, collards, cream, eel. egg yolk, endive, fennel, kale, kidney (beef. pig. sheep), leek greens, lettuce (butterhead and romaine), liver (pork), mango, margarine, melons (yellow), milk (dried), mustard, nectarine, peach, pumpkin, squash (acorn, butternut, hnbhard), sweet potato, tomato, watercress, whitefish. 

Unusual features of vitamin A as observed by some investigators include (1) decreases serum cholesterol in large-quantity administration (chicks) (2) dietary protein required to mobilize liver reserves of vitamin A (3) decreased quantities in tumors (4) coenzynre Q10 accumulates in A-deficient rat liver (5) Ubichromenol-50 accumulation in A-deficient rat liver (6) retinoic acid functions as vitamin A except for visual and reproductive functions (7) anti-infection properties and anti-allergic properties (8) decreases basal metabolism (9) detoxification of poisons in the liver aided by vitamin A and (10) vitamin A is involved in triose —> glucose conversions. 

Oily fish and extracted fish oils contain high concentrations of EPA and DHA. Fish oils also contain vitamins A and D. Oil derived from cod, halibut, or shark liver, or from fish body, typically contains about 200 mg/ml of long-chain omega-3 fatty acids. In addition, cod liver oil provides 50 pg/ml of vitamin A and 2 pg/ml of vitamin D. Many fish oil supplements are artificially enriched with omega-3 fatty acids. 

Liver and kidneys are excellent sources of vitamins A and B12, folate, niacin, iron, and other minerals... 

There is little in the literature relative to vitamin A and colon cancer in human populations. Experimental animal studies, however, strongly suggest that vitamin A deficiency may have a role in this type of cancer. We have shown that a deficiency of vitamin A increased DMH-induced tumors and shortened the lag time for induction, compared to normally supplemented controls (72). More recently (73) we have confirmed a protective role for vitamin A in colon carcinogenesis (Table XVII). Furthermore, we have shown (74) that vitamin A deficiency can result in colon tumors in rats given aflatoxin (AFB ) which is normally a liver carcinogen (Table XVIII). The colon tumors associated with the hepatocarcinogen AFB.. appear to be a result of differences in metabolism and binding of AFB or its metabolite ) to colon DNA under conditions of vitamin A deficiency (75). 

The liver distributes fat-soluble vitamins or their precursors throughout the organism. Whereas vitamins A and D are transported away from the liver in... 

When vitamin A stores are adequate, the liver secretes retinol bound to retinol-binding protein (RBP) into the circulation to provide tissues with a constant supply of vitamin A. In the circulation, the retinol-RBP complex is found bound to another circulating protein of hepatic origin, transthyretin (TTR). TTR also binds thyroid hormone and consequently plays a role in the transport of both vitamin A and thyroid hormone. The molecular size of the retinol-RBP complex is quite small, and the formation of the... 

Figure 29-4. Stellate cell lipid droplets present in a biopsy obtained from the liver of a patient experiencing vitamin A toxicity. Image obtained from electron microscopy of a biopsied human liver showing the characteristic lipid droplets (LD) found in hepatic stellate cells (SC).These lipid droplets are highly enriched in vitamin A, and the size and number of lipid droplets is influenced by dietary vitamin A intake and nutritional status. In this image of a human stellate cell, the nucleus (N) is compressed by the surrounding lipid droplets, and very little cell cytoplasm within the stellate cell can be seen in this view.Adjoining the stellate cell are two hepatocytes (H).

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