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Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Due to their known effects on bone metabolism, Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures. OBJECTIVES: To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, BIOSIS, CINAHL, HealthPLAN, Dissertation Abstracts, Index to UK Theses, Current Contents, and bibliographies of identified trials and reviews. Trials were also obtained from the Cochrane Musculoskeletal Injuries Group trials register. Date of the most recent search: December 1995. SELECTION CRITERIA: Any randomised or quasi-randomised trial which compared Vitamin D or a Vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with fracture as an outcome, in elderly men or women with involutional or post-menopausal osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a seven item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. MAIN RESULTS: Fourteen trials recording 13 different comparisons were included. In the only trial of Vitamin D alone, protection against hip fracture was not confirmed. Two regimens, each represented by one large trial, which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were: 1) Oral Vitamin D when accompanied by calcium supplementation. 2) 1,25 dihydroxy Vitamin D (calcitriol). This appeared more effective than calcium in a direct comparison. Regimens showing limited evidence of efficacy in reducing the incidence of vertebral deformity were: 1) 1,25 dihydroxy Vitamin D (calcitriol), which appeared more effective than calcium in one large trial, and more effective than placebo from pooled results of two small trials. 2) Oral 1-alpha hydroxy Vitamin D (alfacalcidol), when administered with calcium supplements (two small trials, which lacked power to confirm a possible effect). Hypercalcaemia and gastro-intestinal symptoms, reported in less than 5% of participants, were slightly more common when Vitamin D analogues were taken. However, the risk of death was marginally less. REVIEWER'S CONCLUSIONS: Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further randomised trials with economic evaluation are desirable before community fracture prevention programmes employing Vitamin D supplementation can be confidently introduced.

Aged↗

Plasma and milk concentrations of vitamin D3 and 25-hydroxy vitamin D3 following intravenous injection of vitamin D3 or 25-hydroxy vitamin D3.

Plasma levels of vitamin D3 or 25-hydroxyvitamin D3 in ewes after administration of a single massive intravenous dose of vitamin D3 (2 X 10(6) IU) or 25-hydroxy vitamin D3 (5 mg) were determined at zero, one, two, three, five, ten and 20 days postinjection. In six ewes injected with vitamin D3 conversion of vitamin D3 to 25-hydroxy vitamin D3 resulted in a six-fold increase in the plasma 25-hydroxy vitamin D3 level within one day. Elevated levels were maintained until day 10 but by day 20 a substantial decline in the plasma 25-hydroxy vitamin D3 level had occurred. Peak levels of vitamin D3 were reached one day after injection and then continuously declined until day 20. Administration of 25-hydroxy vitamin D3 increased plasma concentrations of 25-hydroxy vitamin D3 to fivefold higher levels than those observed when vitamin D3 was injected, with approximately threefold higher levels of 25-hydroxy vitamin D3 maintained for five days. On day 10 and day 20 ewes which were injected with 25-hydroxy vitamin D3 still maintained plasma levels of 25-hydroxy vitamin D3 which were twice as high as those of ewes injected with vitamin D3. In six ewes injected with vitamin D3, a sharp increase in vitamin D3 level in milk occurred within one day and more than a tenfold elevation of milk vitamin D3 concentrations were maintained for ten days. By 20 days the milk vitamin D3 level had returned to preinjection levels. These observations suggest that indirect supplementation of the suckling ruminant with vitamin D3 may be achieved through maternal injection and subsequent mammary transfer.

Animals↗

Biokinetics of dietary RRR-alpha-tocopherol in the male guinea pig at three dietary levels of vitamin C and two levels of vitamin E. Evidence that vitamin C does not "spare" vitamin E in vivo.

The net rates of uptake of "new" and loss of "old" 2R,4'R,8'R-alpha-tocopherol (RRR-alpha-TOH, which is natural vitamin E) have been measured in the blood and in nine tissues of male guinea pigs over an eight week period by feeding diets containing deuterium-labelled alpha-tocopheryl acetate (d6-RRR-alpha-TOAc). There was an initial two week "lead-in" period during which 24 animals [the "high" vitamin E (HE) group] received diets containing 36 mg of unlabelled (d0) RRR-alpha-TOAc and 250 mg of ascorbic acid per kg diet, while another 24 animals [the "low" vitamin E (LE) group] received diets containing 5 mg d0-RRR-alpha-TOAc and 250 mg ascorbic acid per kg diet. The HE group was then divided into three equal subgroups, which were fed diets containing 36 mg d6-RRR-alpha-TOAc and 5000 mg [the "high" vitamin C (HEHC) subgroup], 250 mg [the "normal" vitamin C (HENC) subgroup] and 50 mg [the "low" vitamin C (HELC) subgroup] ascorbic acid per kg diet. One animal from each group was sacrificed each week and the blood and tissues were analyzed for d0- and d6-RRR-alpha-TOH by gas chromatography-mass spectrometry. The LE group was similarly divided into three equal subgroups with animals receiving diets containing 5 mg d6-RRR-alpha-TOAc and 5,000 mg (LEHC), 250 mg (LENC) and 50 mg (LELC) ascorbic acid per kg diet with a similar protocol being followed for sacrifice and analyses. In the HE group the total (d0(-) + d6-) RRR-alpha-TOH concentrations in blood and tissues remained essentially constant over the eight week experiment, whereas in the LE group the total RRR-alpha-TOH concentrations declined noticeably (except in the brain, an organ with a particularly slow turnover of vitamin E). There were no significant differences in the concentrations of "old" d0-RRR-alpha-TOH nor in the concentrations of "new" d6-RRR-alpha-TOH found in any tissue at a particular time between the HEHC, HENC and HELC subgroups, nor between the LEHC, LENC and LELC subgroups. We conclude that the long-postulated "sparing" action of vitamin C on vitamin E, which is well documented in vitro, is of negligible importance in vivo in guinea pigs that are not oxidatively stressed in comparison with the normal metabolic processes which consume vitamin E (e.g., by oxidizing it irreversibly) or eliminate it from the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Vitamin A and vitamin E status of rural preschool children in West Java, Indonesia, and their response to oral doses of vitamin A and of vitamin E.

Vitamin A and E status was studied in five groups (satisfactory growth, reduced growth, night blindness, Bitot's spots, and corneal xerosis) of rural Indonesian preschool children. All groups except corneal xerosis showed satisfactory weight-height ratios. Initial serum retinol values were less than 0.35 mumol/L in 34% of all children. After oral administration of 24.4 mumol vitamin A, mean serum retinol values rose from 0.42 to 0.70 mumol/L at 10 d. After oral treatment of children with 244 or 314 mumol vitamin A, mean serum retinol remained greater than 0.56 mumol/L for 165 d. Of particular note were the low mean initial serum alpha-tocopherol concentrations (6.3 mumol/L) and alpha-tocopherol-total lipid ratios (1.5 mumol/g). Total serum lipids fell in the normal range. Oral administration of 84 mumol vitamin E raised serum alpha-tocopherol and alpha-tocopherol-total-lipid ratios by 46 and 44%, respectively. Thus, vitamin E inadequacy, which impairs vitamin A absorption and storage, may well contribute to the high incidence of clinical vitamin A deficiency in West Javan children.

Administration, Oral↗

Routine clinical determination of carotene, vitamin E, vitamin A, 25-hydroxy vitamin D3 and trans-vitamin K1 in human serum by straight phase HPLC.

A universal extraction procedure is described for fat-soluble vitamins in human serum. Methods are presented for routine quantitative analysis by isocratic straight phase HPLC with UV-detection of (alpha + beta)-carotene, vitamin E (alpha-tocopherol) and vitamin A (all-trans-retinol) in one single run, and of vitamin K1 (trans-phylloquinone) and 25-hydroxy vitamin D3 after sample clean-up using disposable reversed-phase cartridges. The limits of detection, precisions and selectivities of the developed assays are shown to be satisfactory after more than three years' experience. The routine clinical determination of fat-soluble vitamins can be performed in less than 5 mL of serum. Analyses of external quality control and randomly taken outpatient samples are shown to be of great value in assessing laboratory performance.

Calcifediol↗

Effects of vitamin D3, 25(OH) vitamin D3, 24,25(OH)2 vitamin D3, and 1,25(OH)2 vitamin D3 on the in vitro intestinal calcium absorption in the marine teleost, Atlantic cod (Gadus morhua).

The role of vitamin D3, 25(OH) vitamin D3, 24,25(OH)2 vitamin D3, and 1,25(OH)2 vitamin D3, in the regulation of calcium absorption across the intestine in the marine teleost, Gadus morhua, was investigated. The intestine was perfused, in vitro, both vascularly and through the intestinal lumen, and the calcium influx was measured using 45Ca. Vitamin D3 and its metabolites were tested in perfusate concentrations of 10 ng.ml-1.25(OH)D3 increased the intestinal calcium uptake by 65%, while 24,25(OH)2D3 decreased it by 36%. Vitamin D3 and 1,25(OH)2D3, on the other hand, did not affect the calcium influx across the intestinal mucosa. This indicates that 25(OH)D3 and 24,25(OH)2D3 may be active regulators of calcium transport across the intestine of Atlantic cod.

24,25-Dihydroxyvitamin D 3↗

Foods predictive of nutrient intake in Chinese diet in Taiwan: II. Vitamin A, vitamin B1, vitamin B2, vitamin C and calcium.

Dietary consumption data obtained by food weighing for 539 households in Taiwan in 1980-1981 were used to search for predictor foods of individual intake of several vitamins and calcium. Stepwise multiple regression analysis was carried out on food items that were univariately and significantly associated with nutrient intakes, to screen for the important predictors. Less than ten foods were enough to explain more than 90% of the interperson variation for vitamin A, vitamin B1, and vitamin B2. For vitamin C and calcium, 20 food items could explain only 87% of the variation. Salt, brown sugar, and soy bean sauce were selected among calcium predictors. The information on foods predictive of nutrient intake is useful in designing food frequency questionnaires and materials for nutrition education. Although this paper provides such information for Chinese living in Taiwan, some issues described (such as the need to assess spices) may have been overlooked and could be generalized to populations using stir-frying as a major cooking method.

Ascorbic Acid↗

Excess vitamin A and the metabolism of carbohydrates: variation of enzyme activities in gingiva of rats submitted to excess vitamin A, vitamin A plus cortisol and vitamin A plus ascorbic acid.

The effect of 1 to 5 doses of 15,000 I.U. of vitamin A on some enzymes of the carbohydrate metabolism in gingival tissue from rats was studied. Vitamin A feeding resulted in a significant increase in the activities of hexokinase and pyruvate kinase with the different doses tested. A reduction in the activity of phosphofructokinase was observed with 2 and 4 doses. The administration of ascorbic acid along with vitamin A, did not prevent the effects of vitamin A on the activities of the enzymes studied. The data on the enzyme activities in the groups simultaneously fed on vitamin A and cortisol may indicate an additive effect of these compounds.

Animals↗

High-performance liquid chromatography of fat-soluble vitamins: separation and identification of vitamins D2 and D3 and their isomers in food samples in the presence of vitamin A, vitamin E and carotene.

Vitamins D2 and D3 and their corresponding previtamins and provitamins were resolved by reversed-phase high-performance liquid chromatography using a ternary solvent system (acetonitrile-methanol-water) pumped according to a gradient elution programme. The D vitamins were also resolved in the presence of other lipid-soluble vitamins (A, E and K1) and carotene. The peaks were monitored with a UV-visible variable-wavelength detector and were detected at their maximum absorbance, resulting in maximum sensitivity. Lipid-soluble vitamins and carotene were resolved in extracts obtained from oils and butter, thus permitting their identification in a single chromatographic run.

Butter↗

[Methods for determination of vitamins by means of high performance liquid chromatography (HPLC). I. Determination of vitamin D in vitamin concentrates, vitamin mixtures and mineral feedstuffs].

A method is described for the determination of vitamin D in vitamin-concentrates, -mixtures, and mineral feedstuffs. After saponification of the sample, vitamin D is extracted and purified on two columns. Vitamin D is separated by HPLC and determined photometrically.

Chromatography, High Pressure Liquid↗

Vitamin concentration and function of leukocytes from dairy calves supplemented with vitamin A, vitamin E, and beta-carotene in vitro.

Blood neutrophils and pulmonary alveolar macrophages, isolated from calves at 3 and 6 wk of age, were cultured in medium without added vitamins or supplemented with 100 micrograms/dl of vitamin A, 1000 micrograms/dl of vitamin E, 100 micrograms/dl of vitamin A plus 1000 micrograms/dl of vitamin E, or .25 micrograms/dl of beta-carotene plus 1000 micrograms/dl of vitamin E. Macrophage bactericidal activity improved with supplementation of vitamins A plus E compared with supplementation of beta-carotene plus E or vitamin E at wk 3. Neutrophil bactericidal activity decreased with all vitamin E treatments at wk 3 and with vitamins E or A plus E at wk 6. Neutrophil phagocytosis improved at wk 3 with supplementations of vitamins A, E, and A plus E. The chemotactic index improved with beta-carotene and vitamin E compared with vitamin E alone at wk 3 and at wk 6 with vitamin E compared with vitamin A and control treatments. Retinol content of neutrophils varied at wk 3, but, by wk 6, cells supplemented with vitamins A, E, or A plus E had greater retinol concentrations than control cells. Neutrophil alpha-tocopherol concentrations at wk 3 increased from those of controls with supplementation of vitamin E or beta-carotene and vitamin E, but, at wk 6, vitamin E-supplemented cells were different only from vitamin A-supplemented cells. These data suggest that optimal plasma concentrations of vitamins A and E exist for leukocyte function.

Animal Feed↗

Vitamin E, vitamin B-6, vitamin B-12, and folate status of gastric bypass surgery patients.

The vitamin E, vitamin B-6, vitamin B-12, and folate status of 22 gastric bypass subjects aged 23 to 60 years was evaluated before surgery and at 6 and 12 months after surgery. Before surgery, 77% of subjects had adequate plasma vitamin E levels; 36%, adequate plasma pyridoxal phosphate levels; 100%, adequate plasma vitamin B-12 levels; and 45%, adequate plasma folate levels. The food intake of all subjects was sharply reduced after surgery. After surgery, subjects were classified into three vitamin supplement groups on the basis of average daily vitamin supplement intake. Subjects taking higher levels of supplements containing the vitamins in question had significantly higher plasma concentrations of the vitamins than those taking low or moderate levels. The mean plasma vitamin values in the moderate supplement group were indicative of adequate status for all vitamins, but plasma vitamin B-12 levels at 12 months post-surgery were significantly lower than pre-surgery levels. In the low supplement group, mean plasma vitamin levels were in or near marginal or deficient ranges. The majority of subjects consuming supplements of vitamin E, vitamin B-6, and folate near the US RDA maintained normal vitamin status. Subjects taking more than 100 micrograms vitamin B-12 daily had adequate vitamin B-12 status. Significant correlations (r = .67 to .94) were observed between vitamin supplement levels and the respective plasma vitamin concentrations.

Adult↗

Vitamin D therapy of osteoporosis: plain vitamin D therapy versus active vitamin D analog (D-hormone) therapy.

Normal intestinal calcium (Ca) absorption is an essential feature of bone homeostasis. As with many other organ systems, intestinal Ca absorption declines with aging, and this is one pathological factor that has been identified as a cause of senile osteoporosis in the elderly. This abnormality leads to secondary hyperparathyroidism, which is characterized by high serum parathyroid hormone (PTH) and an increase in bone resorption. Secondary hyperparathyroidism due to poor intestinal Ca absorption has been implicated not only in senile osteoporosis but also in age-related bone loss. Accordingly, in population-based studies, there is a gradual increase in serum PTH from about 20 years of age onward, which constitutes a maximum increase at 80 years of age of 50% of the basal value seen at 30 years of age. The cause of the increase in PTH is thought to be partly due to impaired intestinal Ca absorption that is associated with aging, a cause that is not entirely clear but at least in some instances is related to some form of vitamin D deficiency. There are three types of vitamin D deficiency: (1) primary vitamin D deficiency, which is due to a deficiency of vitamin D, the parent compound; (2) a deficiency of 1,25(OH)(2)D(3) resulting from decreased renal production of 1,25(OH)(2)D(3); and (3) resistance to 1,25(OH)(2)D(3) action owing to decreased responsiveness to 1, 25(OH)(2)D(3) of target tissues. The cause for the resistance to 1, 25(OH)(2)D(3) could be related to the finding that the vitamin D receptor level in the intestine tends to decrease with age. All three types of deficiencies can occur with aging, and each has been implicated as a potential cause of intestinal Ca malabsorption, secondary hyperparathyroidism, and senile osteoporosis. There are two forms of vitamin D replacement therapies: plain vitamin D therapy and active vitamin D analog (or D-hormone) therapy. Primary vitamin D deficiency can be corrected by vitamin supplements of 1000 U a day of plain vitamin D whereas 1,25(OH)(2)D(3) deficiency/resistance requires active vitamin D analog therapy [1, 25(OH)(2)D(3) or 1alpha(OH)D(3)] to correct the high serum PTH and the Ca malabsorption. In addition, in the elderly, there are patients with decreased intestinal Ca absorption but with apparently normal vitamin D metabolism. Although the cause of poor intestinal Ca absorption in these patients is unclear, these patients, as well as all other patients with secondary hyperparathyroidism (not due to decreased renal function), show a decrease in serum PTH and an increase in Ca absorption in response to therapy with 1, 25(OH)(2)D(3) or 1alpha(OH)D(3). In short, it is clear that some form of vitamin D therapy, either plain vitamin D or 1,25(OH)(2)D(3) or 1alpha(OH)D(3), can be used to correct all types of age-dependent impairments in intestinal Ca absorption and secondary hyperparathyroidism during aging. However, from a clinical standpoint, it is important to recognize the type of vitamin D deficiency in patients with senile osteoporosis so that primary vitamin D deficiency can be appropriately treated with plain vitamin D therapy, whereas 1,25(OH)(2)D(3) deficiency/resistance will be properly treated with 1,25(OH)(2)D(3) or 1alpha(OH)D(3) therapy. With respect to postmenopausal osteoporosis, there is strong evidence that active vitamin D analogs (but not plain vitamin D) may have bone-sparing actions. However, these effects appear to be results of their pharmacologic actions on bone formation and resorption rather than through replenishing a deficiency.

Aging↗

Effect of an oral dose of vitamin E on the vitamin E and cholesterol content of tissues of the vitamin E-deficient rat.

Weanling rats (female Sprague-Dawley) were fed until maturity a vitamin E-deficient diet or the deficient diet supplemented with 66 IU RRR-alpha-tocopheryl acetate/kg. Vitamin E, vitamin E quinone and total cholesterol levels in plasma, liver, paraovarian adipose tissue, lung, ovary and adrenal tissue were measured by high performance liquid chromatography. Vitamin E levels were greatly diminished, but cholesterol levels were unchanged in all tissues except adipose tissue of animals fed the deficient diet. Vitamin E-deficient animals received a single oral dose of 2 or 16.7 mg of RRR-alpha-tocopherol, and tissues were examined at 12 and 48 h. Plasma and liver formed a vitamin E pool that peaked at 12 h, had a high vitamin E/cholesterol ratio at 12 h and contained only trace amounts of vitamin E quinone. Adipose tissue, lung, ovary and adrenal concentrated vitamin E throughout the 48-h period, had low vitamin E/cholesterol ratios and contained small but significant amounts of vitamin E quinone. Vitamin E levels (micrograms/gram) at 48 h in lung, ovary and adrenal were higher than the vitamin E level in liver but the liver contained much more vitamin E (micrograms/organ) than the other tissues combined. Cholesterol levels (micrograms/gram) in plasma and liver decreased 45 to 55% in a dose- and time-dependent manner when a single oral dose of vitamin E was administered to deficient animals. Cholesterol levels in adipose tissue, lung and ovary were unchanged while the cholesterol level in adrenal increased 122% in a time-dependent manner with a single oral dose of vitamin E. These data show that a single oral dose of vitamin E has a profound effect on cholesterol levels in short-time experiments with the vitamin E-deficient rat. This rat model is appropriate for studies on the relationship between vitamin E and cholesterol metabolism in plasma, liver and the adrenal.

Adipose Tissue↗

Synergistic action of vitamin E and vitamin C in vivo using a new mutant of Wistar-strain rats, ODS, unable to synthesize vitamin C.

It is well known that vitamins E and C exhibit synergistic action in in vitro systems, but with regard to in vivo systems, much of the available data are confusing. To elucidate this problem we used a new mutant of Wistar-strain rats that cannot synthesize vitamin C, namely, ODS rats. Two experiments were planned: (1) during development of vitamin E deficiency, whether vitamin C could spare the consumption of vitamin E; and (2) under conditions of a regular level of vitamin E intake, whether different dose levels of vitamin C can affect vitamin E concentration in tissues. The results obtained show that with vitamin C intake, higher levels of vitamin E were deposited in tissues in both experiments. With the development of vitamin E deficiency, rats in the group with a higher dose of vitamin C deposited higher concentrations of alpha-tocopherol. With simultaneous administration of vitamin E and vitamin C to the same mutant rats, the rats in the group with a higher dose of vitamin C deposited higher levels of vitamin E in all tissues tested. Thus, we concluded that vitamin C can spare the consumption of vitamin E in vivo as well as in vitro.

Animals↗

Vitamin A during lactation: relationship of maternal diet to milk vitamin A content and to the vitamin A status of lactating rats and their pups.

We have investigated the effects of maternal vitamin A intake during pregnancy and lactation or during lactation alone on the concentration of vitamin A in rat's milk and on vitamin A levels in plasma and liver of dams and their pups. Groups of Sprague-Dawley rats were fed diets having either a high vitamin A content [15 retinol equivalents (R.E.)/g diet] or a low vitamin A content (0.6 R.E./g) for 42 d, including 7-8 d prior to pregnancy, pregnancy, and for 14 d of lactation. The concentration of vitamin A in milk on d 14 of lactation was significantly greater on the high vitamin A diets [114 +/- 16 micrograms/dl (mean +/- SEM; n = 8) versus 52 +/- 7.3 micrograms/dl (n = 11), P less than 0.005]. However, milk vitamin A concentration on d 1 of lactation did not vary with maternal vitamin A intake during pregnancy. In a second study in which supplementation with vitamin A (30 R.E./g diet) was begun on d 1 postpartum, the milk vitamin A content increased progressively with duration of lactation. Maternal plasma vitamin A concentrations did not differ between rats fed the higher or lower vitamin A diets. However, liver vitamin A concentrations both of dams and of their 14-d-old pups were significantly higher when dams were fed the higher vitamin A diets during pregnancy and/or lactation. The results of these studies indicate that the transfer of vitamin A from mother to offspring by milk and the vitamin A status of dams and their suckling neonates is influenced by maternal vitamin A intake during lactation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Population Groups↗

Interdependence of serum concentrations of vitamin K1, vitamin E, lipids, apolipoprotein A1, and apolipoprotein B: importance in assessing vitamin status.

Vitamin E (alpha-tocopherol) and vitamin K1 (phylloquinone) are fat-soluble vitamins and are important nutrients in health and disease. In this study serum concentrations of vitamin E and vitamin K1, lipids and apolipoproteins A1 and B were measured in neonates, normal and hyperlipidaemic individuals in an attempt to establish their interrelationships. A high degree of correlation was observed between the concentrations of the vitamins and those of lipids and apolipoproteins (r ranged from 0.42 to 0.92; p<0.001). Stepwise linear regression methods determined that serum concentrations of both vitamin E and vitamin K1 could best be predicted by using equations excluding lipids but containing only apolipoprotein A1 and B concentrations. Correlation coefficients between predicted and measured values were 0.89 for serum vitamin E, and 0.83 for serum vitamin K1 concentrations. To test the validity of the derived formulae, measured and estimated vitamin K1 and vitamin E concentrations in serum were determined in another group of neonates, normal adults and hypercholesterolemic adults and the comparisons were shown to be very good. These results indicate that the serum levels of both vitamins depend critically on the concentration of the lipoprotein carriers, apolipoproteins A1 and B. Hence, in order to identify variations in serum vitamin K1 and vitamin E concentrations, which are independent of variations in carrier concentration, it will be necessary to express these serum vitamins as ratios of vitamins to apolipoprotein A1 and B carriers.

Adult↗

Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man.

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.

Adult↗