Assessment of Vitamin D Status

Osteocalcin is induced in osteoblasts by calcitriol, and circulating osteocalcin can be used as an index of calcitriol action and metabolic bone disease. In rachitic children, the plasma concentration of osteocalcin is lower than in controls, tmd rises on therapy, remtdning high until there is radiologictd evidence of cure. However, plasma osteocalcin cem be undetectably low in normal subjects with adequate vittunin D status, so this does not provide a useful indication of deficiency (Greig et td., 1989). 

The plasma concentration of calcidiol is the most sensitive and usefiil index of vitamin D status, and is correlated with elevated plasma parathyroid hormone and alkaline phosphatase activity (Table 3.4). As shown in Table 3.2, the reference range of plasma calcidiol is between 20 to 150 nmol per L, with a twofold seasonal variation in temperate regions. Concentrations below 20 nmol per L are considered to indicate impending deficiency, and osteomalacia is seen in adults when plasma calcidiol falls below 10 nmol per L. In children, clinical signs of rickets are seen when plasma calcidiol faUs below 20 nmol per L. The plasma concentration of calcitriol does not give a useful indication of vitamin D status. The reference range is between 38 to 144 pmol per L and is maintained because of the stimulation of calcidiol 1-hydroxylation by parathyroid hormone secreted in response to faUing concentrations of calcium (Holick, 1990). 

Tabie 3.4 Plasma Concentrations of Calcidiol, Alkaline Phosphatase, Calcium, and Phosphate as Indices of Nutritional Status 

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Biochemistry of Vtamin D Assessment of Vtamin D Status Action of 1 -Dihydroxyvitamin 03 in Regulating Transcriptkm Vitamin D Deficiency Phosphate Metabolism Treatment of Vitamin D Ddidency and Hazards of High Intake... 

Kudlacek S, Schneider B, Peterlik M, Leb G, Klaushofer K, Weber K, Woloszczuk W and Willvonseder R (2003) Assessment of vitamin D and calcium status in healthy adult Austrians. Eur J Clin Invest 33 323-331. 

Haskell MJ, Handelman GJ, Peerson JM, Jones AD, Rabbi MA, Awal MA, Wahed MA, Mahalanabis D, Brown KH (1997) Assessment of vitamin A status by the deuterated-retinol-dilution technique and comparison with hepatic vitamin A concentration in Bangladeshi surgical patients. Amer J Clin Nutr 66 61-1A Haskell MJ, Islam MA, Handelman GJ, Peerson JM, Jones AD, Wahed MA, Mahalanabis D, Brown KH (1998) Plasma kinetics of an oral dose of [ H4]retinyl acetate in human subjects with estimated low or high total body stores of vitamin A. Amer J Clin Nutr 68 90-95... 

Vitamin status can be assessed by a direct test for the levels of 25-(OHin the serum, This competitive binding test involves three components (1) a serum sample, (2) radioactive 25-hydroxy[ Hjvitamin Dj, and (3) vitamin D-binding protein. The source of vitamin D-binding protein may be sheep serum. The functional tests for deternrination of vitamin D irvdude the diagnostic tests for rickets and osteomalacia. A test for osteomalacia, for example, may include measurement of the width of the osteoid in a bone biopsy. The osteoid is described later. 

Vitamin D deficiency remains a cause of osteomalacia in the elderly, houschound or institutionalized patients. Vitamin D status can be assessed by measurement of the main circulating metabolite, 25-hydroxycholecalciferol. In severe osteomalacia due to vitamin I) deficiency, senim calcium will fall, and there will be an appropriate increase in PTH secretion. Alkaline phosphata.se will be elevated. 

Osteomalacia is the name given to defective bone mineralization in adults (Fig. 2). Rickets is chiiractcrized by defects of bone and cartilage mineralization in children. Vitamin D deficiency was once the most common reason for rickets and osteomalacia, but the addition of vitamin D to foodstuffs has almost eliminated the condition except in the elderly or housebound. the institutionalized, and in certain ethnic groups. Elderly Asian women with a predominantly vegetarian diet are particularly at risk. Vitamin D status can be assessed by measurement of the main circulating metabolite. 23-hydroxycholecalciferol. in a scrum specimen. The metabolism of vitamin D is shown in Figure 3. 

However, results obtained by Koo et al. (1991) indicate that low to moderate lead exposure (average lifetime PbB level range of 4.9-23.6 pg/dL, geometric mean of 9.8 pg/dL, n=105) in young children with adequate nutritional status, particularly with respect to calcium, phosphorus, and vitamin D, has no effect on vitamin D metabolism, calcium and phosphorus homeostasis, or bone mineral content. The authors attribute the difference in results from those other studies to the fact that the children in their study had lower PbB levels (only 5 children had PbB levels >60 pg/dL and all 105 children had average lifetime PbB levels <45 pg/dL at the time of assessment) and had adequate dietary intakes of calcium, phosphorus, and vitamin D. They concluded that the effects of lead on vitamin D metabolism observed in previous studies may, therefore, only be apparent in children with chronic nutritional deficiency and chronically elevated PbB levels. Similar conclusions were reached by IPCS (1995) after review of the epidemiological data. 

Before transplant, BMD should be measured and vitamin D and gonadal status assessed. Bone-healthy lifestyle changes and therapy should be instituted as needed (see Fig. 88-4) and hypogonadism corrected before and after transplant. Intermittent pamidronate has decreased bone loss in most transplant recipients." Use of bisphosphonates in children and when creatinine clearance is less than 30 mL/min is being explored. Glucocorticoid doses should be... 

Vitamin E Status of Humans. As hypovitaminosis E is a rare event (see D), a routine assessment of the vitamin E status in humans is not required but only justified for risk groups (e.g., prematures) and as part of studies on the chemoprevention of diseases presumably involving oxidative stress as an etiological factor, e.g., cancer, atherosclerosis, and cataract. Knowledge about the in vivo fate of vitamin E (see C) will guide in the choice of samples to be analyzed. The most common, easily obtainable biological matrix for the determination of vitamin E and of a-tocopherol in particular is plasma/serum. Plasma levels of Y-tocopherol, which is more abundant in foods, are of little importance except... 

Flavins are lost from the body as intael riboflavin, rather than as a breakdown product of riboflavin. Hence, vitamin status may be assessed by measuring the level of urinary riboflavin. Generally, the loss of 30 ig of riboflavin/g creatinine or less per day indicates a deficiency. This metht>d of assessment is not preferred because it is influenced by a number of factors unrelated to vitamin status. Another problem with this method is its great sensitivity to a short-term deficiency thus, it does not necessarily reflect the true concentrations of FAD and FMN in tissues. The most reliable way to assess riboflavin status is by a functional test. The test involves the assay of glutathione reductase, using red blood cells as the source of... 

Talwar D, Davidson H, Cooney J, St JO Reilly D. Vitamin B(l) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC comparison with erythrocyte transketolase activation assay. Clin Chem 2000 46 704-10. 

Considerable uncertainty and controversy exists concerning the folate requirement for humans. Hie review of data concerning the human folate requirement by the Food and Nutrition Board (1989) suggests that the daily maintenance requirement is 100-200 fig of avaUable folic acid equivalents. The 1989 RDAs were reduced to 200 and 180 fig for adult men and women, respectively, from the previous RDA of 400 on the basis of such evidence (Food and Nutrition Board, 1989). Similarly, the Canadian RDA for folate was set at 3 /ig/kg body wt or 210 fig for a 70-kg individual. These lower RDAs may be inadequate for certain population groups, however (Sauberlich, 1990 Bailey, 1992 McPartlin etai, 1 3). It is currently difficult or impossible to predict the quantitative effect on folate nutritional status of factors such as (a) changes in folate intake, (b) differences in folate bioavailability, (c) effects of pregnancy and lactation on folate requirements, and (d) pharmaceuticals with antifolate properties. In addition, the development of mathematical models would improve our ability to evaluate methods of nutritional status assessment for this vitamin. 

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