Vitamin tissue reserves

Tissue reserves of retinoids in the healthy adult are sufficiently large to require long-term dietary deprivation to induce deficiency. Vitamin A deficiency occurs more commonly in chronic diseases affecting fat absorption, such as biliary tract or pancreatic insufficiency, sprue, Crohn s disease involving the terminal ileum, and portal cirrhosis deficiency may also occur following partial gastrectomy or during extreme, chronic dietary inadequacy. 

Vitamin E deficiency is not a problem, even among people living on relatively poor diets. In depletion studies, very low intakes of vitamin E must be maintained for many months before there is any significant fall in circulating a-tocopherol, because there are relatively large tissue reserves of the vitamin. 

At intakes in excess of about 100 mg per day, there is quantitative urinary excretion of unmetabolized vitamin C with increasing intake, indicating that tissue reserves are saturated and the renal threshold has been exceeded. It is difficult to justify a requirement in excess of tissue storage capacity. 

Saturation and Intradermal Tests. Ascorbic acid saturation tests, based on observations that subjects with low tissue reserves excreted less of a test dose of vitamin C in the urine than subjects with adequate stores, did not distinguish between varying degrees of deficiency at the lower levels of nutrition. Relatively high plasma levels must be attained before the effect of the renal tubular reabsorption is surpassed and significant excretion occurs (see Section 5). 

That the livers of newborn puppies contain little vitamin A reserve was shown by Busson and Simmonet (1932) by biological assays the liver of the newborn animal was found to be inactive in these experiments, even when that of the dam contained ample quantities. In agreement with these results, Eekelen and WolfI (1936) in analysis of the liver from a newborn pup found a vitamin A concentration of only 6 I.U./gm. Fairly extensive studies on the vitamin A content of hepatic tissue in young dogs only a few months old, and in adult animals have been carried out by Linton and Brownlee (1939). The values observed by these authors, and those re-... 

Over 90% of the vitamin A reserve is found in the liver but substantial amounts are distributed in other tissues. Table VIII gives the concentration of vitamin A and carotenoids in several tissues. Isotope dilution techniques using tritium-labeled vitamin A have been applied to assess total body vitamin A status... 

Corneal ulceration (X3A, X3B), frequently referred to as keratomalacia, is accompanied most frequently by serious protein malnutrition. This may occur even while some body pools of vitamin A remain in the liver because of an ineffective transport system to peripheral tissues. Hence, although corneal involvement is indicative of vitamin A deficiency in ocular cells, it does not invariably reflect markedly inadequate hepatic vitamin A reserves (McLaren et al., 1965a). In these cases, dietary protein more than vitamin A is critical for long-term recovery, but in the short run, vitamin A alone will usually at least arrest further corneal degeneration (Reddy et al., 1979). Because there is no practical way of differentiating those children with adequate from those with exhausted vitamin A stores, when corneal involvement is assessed, treatment... 

In order to restore the tissue reserves, Mollin and Ross (1953b) advise giving five injections of 1000 ftg. in the first few weeks. They realize that unless a method is found for retarding absorption of the injected vitamin much of it will be lost in the urine. They estimate, however, that 200 or 300 fig. from each injection will be retained. More frequent injections of small amounts would be more economical but less convenient. After such intensive initial dosage, a monthly injection of 100 fig. should be more than adequate to maintain serum B12 levels well within the normal range (Mollin and Ross, 1953b). 

Estimates of riboflavin requirements are based on depletion/repletion studies to determine the minimum intake at which there is significant excretion of the vitamin. In deficiency there is virtually no excretion of the vitamin as requirements are met, so any excess is excreted in the urine. On this basis the minimum adult requirement for riboflavin is 0.5-0.8 mg/day. At intakes between 1.1 and 1.6mg/day urinary excretion rises sharply because tissue reserves are saturated. 

It is relatively easy to assess the state of body reserves of vitamin C by measuring the excretion after a test dose. A subject whose tissue reserves are saturated will excrete more or less the whole of a test dose of 500 mg of ascorbate over 6 hours. A more precise method involves repeating the loading test daily until more or less complete recovery is achieved, thus giving an indication of how depleted the body stores were. 

Excretion. Vitamin C is largely excreted in the urine, with the amount excreted controlled by the kidney tubules. When the tissues are saturated, a large amount is excreted but when the tissue reserves are depleted, only a small amount is excreted. Some vitamin C is always excreted by the kidneys even when the tissues are severely depleted. 

Effects of Vitamin A Deficiency.—(1) Failure of Growth.— This is obvious only in young animals. The growth-rate falls off rapidly when the vitamin is withheld and the tissue-reserves have been exhausted. The animal continues to exist at a subnormal weight until secondary disturbances or infections develop. 

When liver vitamin A reserves fall below about 20-30 pg retinol g liver, the secretion of holo-RBP is compromised due to inadequate retinol. Plasma retinol levels begin to fall and, if liver vitamin A continues to decline, plasma levels will fall into the deficient range and will be inadequate to supply retinol to tissues. Essentially all of the vitamin A in liver can be mobilized when it is needed to meet the needs of peripheral tissues. But ultimately, vitamin A intake must increase to bring plasma retinol levels back to the normal range. 

Adults require a maintenance level of vitamin A. The RDA is based on maintaining an adequate level of vitamin A in liver while meeting normal tissue demands. In animals fed a normal vitamin A adequate diet, retinyl esters tend to accumulate as the animal ages, such that it becomes very difficult to induce vitamin A deficiency in adult animals, even by feeding them a diet free of vitamin A. These data imply that tissue reserves readily make up for lapses in the day-to-day intake of vitamin A. As is evident from Table 1, some foods contain an amount of vitamin A well in excess of 100% of the daily value (%DV). 

Based on the body content of 15 pmol (3.7mg) of vitamin Bg per kilogram body weight, and the rate of weight gain, the minimum requirement for infants over the first 6 months of life would appear to be 100 pg (417 nmol) per day to establish tissue reserves. 

As the intake of vitamin A increases, there is an increase in the excretion of metabolites in bile, once adequate liver reserves have been established. However, the biliary excretion of retinol metabolites reaches a plateau at relatively low levels, and it seems likely that this explains the relatively low toxic threshold (Olson, 1986). Vitamin A intoxication is associated with the appearance of both retinol and retinyl esters bound to albumin and in plasma lipoproteins, which can be taken up by tissues in an uncontrolled manner the amount of circulating retinol bound to RBP does not increase. Retinol has a membrane lytic action it was noted in Section 2.2.2.3 that one of the functions of RBP binding seems to be to protect tissues against retinol, as well as to protect retinol against oxidation (Meeks et al., 1981). 

Muscle pyridoxal phosphate is released into the circulation (as pyridoxal) in starvation as muscle glycogen reserves are exhausted and there is less requirement for glycogen phosphorylase activity. Under these conditions, it is potentially available for redistribution to other tissues, especially the liver and kidneys, to meet the increased requirement for gluconeogenesis from amino acids (Black et al., 1978). However, during both starvation and prolonged bed rest, there is a considerable increase in urinary excretion of 4-pyridoxic acid, suggesting that much of the vitamin Be released as a result of depletion of muscle glycogen and atrophy of muscle is not redistributed, but rather is ca-tabolized and excreted (Cobum et al., 1995). 

Vitamin C status is generally assessed by estimating the saturation of body reserves or measuring plasma and leukocyte concentrations of the vitamin. Urinary excretion of hydroxyproline-containing peptides is reduced in people with inadequate vitamin C status, but a number of other factors that affect bone and connective tissue turnover confound interpretation of the results (Bates, 1977). The ratio of deoxypyridinolineipyridinoline compounds derived from collagen cross-links provides a more useful index, but is potentially affected by copper status (Tsuchiya and Bates, 1997). 

The minerals in bones are completely replaced about every seven years, being deposited and withdrawn many times, just like money in a bank account. The body is designed so that minerals and trace elements that play key roles in body activities have a backup reserve in case of emergency. Extra iron, if needed, is stored in the liver, spleen, and bone marrow as ferritin, an iron-phosphorus protein. Sodium reserves are in the bones, stomach walls, and joints.The liver stores a year s supply of vitamin B)2 in case of temporary deficiency in the diet. Fat tissue in the body is also an energy fuel reserve. The body is prepared to deal with short-term deficiencies of most essential nutrients. 

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