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Assessment of thiamin (vitamin B1) and riboflavin (vitamin B2) status in an adult Mediterranean population.

The aim of the present study was to assess the nutritional status for thiamin (vitamin B1) and riboflavin (vitamin B2) in an adult Mediterranean population, in order to identify patterns of intake, groups at risk for deficiency and factors that might influence this risk. A cross-sectional survey was carried out in Andalusia, a western Mediterranean region in southern Spain. Nutrient intakes were studied in a random sample of 3390 subjects (1746 men, 1644 women) who were between 25 and 60 years of age. Blood samples were obtained for biochemical assays in a random subsample of 372 subjects (181 men, 191 women). Food consumption was assessed by 48 h recall. Vitamin B1 and B2 were measured as erythrocyte transketolase and as erythrocyte glutathione reductase activation coefficients, respectively. Energy and vitamin intakes were significantly higher in men than in women. Intakes were below two-thirds of the recommended dietary allowance for vitamin B1 in 7.80 % of the men and 4.50 % of the woman, and were below this level for vitamin B2 in 18.00 % of the men and 11.70 % of the women. Age, educational level, alcohol use and smoking were also associated with differences in the intake of these nutrients. Biochemical analyses showed that vitamin B1 and B2 status was deficient in 6.40 and 5.30 % of the population, respectively. Although factors such as gender, age, level of education, drinking and smoking can have an effect on the risk of inadequate intake of these nutrients, these factors did not affect biochemical indices of nutritional status in the present study.

Adult↗

The response of the dietary anti-oxidants vitamin E and vitamin C to oxidative stress in pre-eclampsia.

The relationship of oxidants and anti-oxidants in preeclampsia with reference to the dietary anti-oxidants vitamin C and vitamin E was investigated. Three groups of patients were studied in the third trimester of pregnancy: normotensives ( n = 32), mild pre-eclamptics ( n = 15) and severe pre-eclamptics ( n = 31) with a group of healthy non-pregnant women ( n = 18) serving as a control. Total anti-oxidant concentration, the concentrations of vitamin C, vitamin E, superoxide dismutase, uric acid and the concentration of total oxidant activity, as reflected by lipid peroxides, were measured in plasma or red blood cells. Total anti-oxidants and vitamin C concentrations were significantly lower in pre-eclamptic patients than in pregnant controls (P < 0.05), with the concentrations in the pregnant controls being significantly lower than in the non-pregnant controls (P < 0.05). There was no significant difference in vitamin E concentration for all four groups. Superoxide dismutase activity was significantly lower in the normal pregnancy group. Lipid peroxides were significantly increased in the three pregnant groups (P < 0.05) with no differences noted between these groups. The relationship of oxidants to anti-oxidants in pregnancy and pre-eclampsia is dependent on many factors but balance appears to be upset in pre-eclampsia. The reduction in anti-oxidant concentrations in pre-eclampsia suggests either a primary deficit or consumption of the anti-oxidants measured. Of the dietary anti-oxidants studied, vitamin C was most affected in pre-eclampsia.

Journal Article↗

Dietary intake of total and glycosylated vitamin B-6 and the vitamin B-6 nutritional status of unsupplemented lactating women and their infants.

The mean dietary intakes of total and glycosylated vitamin B-6, determined from analysis of 3-d diet composites collected from 30 lactating women, were 8.63 +/- 4.04 and 1.33 +/- 0.85 mumol/d (mean +/- SD), respectively. A comparison of linear regression models that either included or excluded dietary glycosylated vitamin B-6 content indicates that the intake of glycosylated vitamin B-6 had little, if any, effect upon maternal plasma pyridoxal 5'-phosphate concentration and maternal urinary excretion of total vitamin B-6 and 4-pyridoxic acid. On the basis of guidelines from the literature for evaluating biochemical indices of vitamin B-6 nutriture, the women appeared to be consuming adequate amounts of the vitamin. The mean breast-milk concentrations of total and glycosylated vitamin B-6 were 733 and 18 nmol/L, respectively. Infant plasma pyridoxal 5'-phosphate concentration was 54 +/- 44 nmol/L (mean +/- SD) and all infants had lengths and weights appropriate for age.

Adult↗

Influence of age and sex on vitamin B-6 vitamer distribution and on vitamin B-6 metabolizing enzymes in Wistar rats.

Vitamin B-6 vitamer distribution and activities of vitamin B-6 metabolizing enzymes were evaluated in aging male and female Wistar rats fed a purified diet (containing 250 g of casein and 6 mg of pyridoxine hydrochloride per kg) from weaning until 31 mo of age. Plasma pyridoxal 5'-phosphate (PLP) concentration became lower with increasing age, with the largest decrease in the 1st yr of life. An age-related change in vitamin B-6 distribution between the various tissues examined was observed: B-6 vitamer content increased in heart and brain, whereas PLP content decreased in gastrocnemius muscle, kidney and liver. The decrease in muscle PLP content occurred in concert with a decrease in muscle glycogen phosphorylase activity. Urinary 4-pyridoxic acid (4-PA) excretion increased with age, especially in female rats, in parallel with an increase in liver pyridoxal oxidase and pyridoxal dehydrogenase activities. Age-related changes in vitamin B-6 distribution were probably not causally related to changes in activity of vitamin B-6 metabolizing enzymes; they were regarded as consequences of changes in protein metabolism. The higher urinary 4-PA excretion in older rats may reflect a lower vitamin B-6 requirement; however, the lower PLP content of gastrocnemius muscle may indicate an age-related decrease in vitamin B-6 body stores.

Aging↗

Vitamin C and other compounds in vitamin C rich food in relation to risk of tuberculosis in male smokers.

To examine whether vitamin C rich food consumption and related vitamin C intake are associated with the risk of tuberculosis, the authors analyzed 167 incident cases of tuberculosis during a median follow-up time of 6.7 years in a clinical trial cohort of 26,975 Finnish men for whom they had baseline dietary data. A highly statistically significant inverse association between calculated vitamin C intake and the incidence of tuberculosis was found, but adjustment for non-dietary factors weakened the association to nonsignificant. Furthermore, the risk of tuberculosis decreased with increasing intake of fruits, vegetables, and berries independent of vitamin C intake. Subjects who had dietary vitamin C intake >90 mg/day and who consumed more than the average amount of fruits, vegetables, and berries had a significantly lower risk of tuberculosis (adjusted relative risk = 0.40; 95% confidence interval 0.24, 0.69). Associations between dietary vitamin C intake and occurrence of various diseases without proper control of confounding have often been interpreted as causal. These findings show that such associations can be confounded even by some other dietary components. Lower tuberculosis incidence in subjects who consumed more fruits, vegetables, and berries poor in vitamin C suggests that other compounds in such a diet may reduce the risk of tuberculosis.

Aged↗

Metabolism of vitamin D2 and vitamin D3 in patients on anticonvulsant therapy.

We examined the effect of short-term treatment with pharmacological doses of vitamin D2 or vitamin D3 on the serum concentration of 1,25(OH)2D metabolites in epileptic patients on chronic anticonvulsant drug therapy. Nine patients were studied before and after treatment with vitamin D2 4000 IU daily for 24 weeks and 10 before and after treatment with vitamin D3 in the same dose. Before treatment the serum concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in epileptics than in normal subjects (P less than 0.01). Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D. The serum concentration of 25(OH)D2 and 25(OH)D increased significantly, whereas there was a small decrease in 25(OH)D3. Vitamin D3 treatment did not change the serum concentration of 1,25(OH)2D3 whereas serum 25(OH)D3 increased significantly. The correlation between the serum ratio of 1,25(OH)2D2/1,25(OH)2D3 and 25(OH)D2/25(OH)D3 estimated on vitamin D2-treated epileptic patients and normal subjects was highly significant (P less than 0.01). The data indicate that the serum concentration of 1,25(OH)2D2 and 1,25(OH)2D3 are directly proportional to the amount of their precursors 25(OH)D2 and 25(OH)D3 and that the concentration of total 1,25(OH)2D is tightly regulated.

25-Hydroxyvitamin D 2↗

Side chain metabolism of 25-hydroxy-[26,27-14C] vitamin D3 and 1,25-dihydroxy-[26,27-14C] vitamin D3 in vivo.

Radioactive CO2 was detected in expired air after the administration of 25-hydroxy-[26,27-14C] vitamin d3 to vitamin D-deficient hypocalcemic rats; 14co2 was also detected after the administration of 1,25-dihydroxy-[26,27-14C] vitamin D3 to rats raised on the same diet. Nephretcomy totally abolished 14CO2 formation after administration of 25-hydroxy-[26,27-14C] vitamin D3 but not after the administration of 1,25-dihydroxy-[26,27-14C] vitamin D3. The production of 14CO2 commenced within 4 hours after injection of 1,25-dihydroxy-[26,27-14C] vitamin D3, suggesting a possible relevance of this reaction to the function of 1,25-dihydroxyvitamin D3. These results at least demonstrate a new metabolic pathway of vitamin D3 metabolism involving the oxidation of a portion of the side chain of 1,25-dihydroxyvitamin D3 to CO2.

Animals↗

Vitamin B6 and vitamin C status in elderly patients with infections during hospitalization.

We have evaluated whether vitamin B6 and C metabolism may be altered by infection in the elderly. Vitamin B6 and C biochemical status has been assessed for times over a period of 21 days (days 0, 7, 14, and 21) in 18 subjects > or = 75 years. The subjects were divided into 3 groups: group I (8 subjects with acute infection), group II (4 malnourished subjects), and group III (6 control subjects). Vitamin B6 status was determined by plasma pyridoxal-5'-phosphate (PLP) and erythrocyte aspartate aminotransferase activation coefficient (alpha-EAST), and vitamin C status by plasma ascorbic acid. During the 3 weeks, vitamins B6 and C values were significantly different between groups: at days 7 and 14, PLP values were significantly higher in group III than in both groups I and II, and alpha-EAST values were significantly higher in group I than in both groups II and III. Plasma ascorbate values were significantly lower in group I than in both groups II and III. These data suggest that an acute catabolic state like infection may influence vitamin B6 and C metabolism. Nevertheless, more work is needed to assert that vitamin B6 and C supplementation may be useful during infection.

Acute-Phase Proteins↗

Effect of maternal dietary vitamin C intake on the level of vitamin C in breastmilk among nursing mothers in Baghdad, Iraq.

The vitamin C content of breastmilk was investigated in a group of nursing mothers attending maternal and child health centers in Baghdad during 1998-2000. Two hundred healthy, nonsmoking, 28- to 38-year-old lactating women were studied. Individual samples of breastmilk were obtained for estimation of vitamin C. Dietary data were collected by using 24-hour food recalls. The mean intake of vitamin C was far below the Food and Agriculture Organization/World Health Organization requirement of 26 +/- 2.13 (SD) mg/day). The vitamin C content of breastmilk was significantly correlated with the maternal intake of vitamin C (r = 0.61, p < .01). The vitamin C content of breastmilk varied with the season. The level was much higher in summer (3.9 +/- 1.05 mg/100 ml) than in winter (3.02 +/- 2.01 mg/100 ml; p < .05). This fluctuation indicates the dependence of breastmilk vitamin C on dietary intake. The results show the need to increase the consumption of vegetables and fruits and to monitor maternal ascorbic acid intake.

Adult↗

Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin.

Sunlight has long been recognized as a major provider of vitamin D for humans; radiation in the UVB (290-315 nm) portion of the solar spectrum photolyzes 7-dehydrocholesterol in the skin to previtamin D3, which, in turn, is converted by a thermal process to vitamin D3. Latitude and season affect both the quantity and quality of solar radiation reaching the earth's surface, especially in the UVB region of the spectrum, but little is known about how these influence the ability of sunlight to synthesize vitamin D3 in skin. A model has been developed to evaluate the effect of seasonal and latitudinal changes on the potential of sunlight to initiate cutaneous production of vitamin D3. Human skin or [3 alpha-3H]7-dehydrocholesterol exposed to sunlight on cloudless days in Boston (42.2 degrees N) from November through February produced no previtamin D3. In Edmonton (52 degrees N) this ineffective winter period extended from October through March. Further south (34 degrees N and 18 degrees N), sunlight effectively photoconverted 7-dehydrocholesterol to previtamin D3 in the middle of winter. These results quantify the dramatic influence of changes in solar UVB radiation on cutaneous vitamin D3 synthesis and indicate the latitudinal increase in the length of the "vitamin D winter" during which dietary supplementation of the vitamin may be advisable.

Alberta↗

Vitamin D3 metabolism in a pig strain with pseudo vitamin D-deficiency rickets, type I.

Vitamin D metabolism was studied in the 'Hannover Pig', a strain which suffers from pseudo vitamin D-deficiency rickets, type I. Animals of this strain are known to be devoid of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase and -24-hydroxylase activities. Pigs with florid rickets and hypocalcaemia were treated with single im injections of 0.25 to 1.25 mg of vitamin D3, doses that have been shown in previous studies to be effective in producing transient healing of rachitic symptoms. The levels of vitamin D3 and its most relevant physiological metabolites in plasma were estimated at intervals before and after this vitamin D3 treatment. Vitamin D3 rose from 14.8 +/- 8.1 to 364 +/- 190 nmol/l (mean +/- SD) 2 to 3 days post injectionem, 25-hydroxyvitamin D3 from 131.0 +/- 46.2 to 1068 +/- 160 nmol/l within 7 days post injectionem. The 1 alpha, 25-dihydroxyvitamin D3 concentration in plasma was elevated from 73.9 +/- 25.0 to 281 +/- 168 pmol/l 2 to 3 days post injectionem and declined continually from that time. 24R,25-dihydroxyvitamin D3 and 25S,26-dihydroxyvitamin D3 levels after treatment showed different responses in different animals being either elevated or unchanged. Clinical healing of the pigs with these doses of vitamin D3 was attributed to the transient rise of 1 alpha,25-dihydroxyvitamin D3 in plasma. It was assumed that 1 alpha,25-dihydroxyvitamin D3 synthesis takes place under these circumstances in extrarenal tissues.

24,25-Dihydroxyvitamin D 3↗

Vitamin D3 levels in certain sheep tissues at various times after the intramuscular administration of vitamin D3.

Twenty crossbred wethers were injected intramuscularly with 1 X 10(6) IU of Vitamin D3 and four killed at the end of each of five time periods (1, 2, 3, 4 and 7 months). The results indicated that in these sheep dosed with this large dose of vitamin D3, their depletion in this liposoluble vitamin was a long process. The rate of uptake varied for the different tissues examined. Among the various tissues, vitamin D3 was stored primarily in the adipose tissue. One month after administration of vitamin D3, levels amounted to approximately 220 ng/g fresh tissue and 7 months later there were still appreciable amounts of D3 (2.5 ng/g fresh tissue). Kidney, pancreas, liver had also accumulated a significant amount of the administered dose (1st month: 58, 32 and 20 ng/g fresh tissue, respectively) which was retained in these sheep's organs for over 4 months (13, 32 and 15 ng/g fresh weight). In three muscles (heart and two skeletal muscles) appreciable amounts of vitamin D3 were recorded, which remained high until 4 months after administration (over 8 ng/g fresh tissue). The lowest uptake was recorded in the skin (9 ng/g the first month and 4 ng/g fresh weight at the end of experiment). All these results show that vitamin D3 was taken up rapidly by various tissues and was retained for a long period of time.

Adipose Tissue↗

Combination of vitamin D metabolites with selective inhibitors of vitamin D metabolism.

1alpha,25(OH)2D3 exerts antiproliferative, differentiating effects on many cell types, including cancer tissues. In most of its target cells, levels of 1alpha,25(OH)2D3 are regulated by local synthesis via CYP27B and metabolism via CYP24. Rapidly induced by vitamin D, CYP24 repeatedly hydroxylates the vitamin D side chain and ultimately terminates hormonal activity. Aiming at increased hormone levels, lifetime and function, numerous vitamin D analogs have been synthesized with structural modifications, which impede oxidation of the vitamin D side chain. Our group followed a different strategy, namely, blocking 1,25(OH)2D3 metabolism with inhibitors of CYP24. As appropriate inhibitors, we exploited compounds termed azoles, which directly bind to the heme iron of the CYPs via an azole nitrogen and to other parts of the substrate site. We synthesized some 400 azoles and tested their potential to selectively inhibit CYP24, but not hormone synthesis by the related CYP27B. Using primary human keratinocyte cultures as the source of CYP24 and CYP27, we discovered some 50 inhibitors of CYP24 with IC50 values in the nanomole range and selectivities up to 60-fold. As the first representative of selective CYP24 inhibitors, VID400 underwent preclinical development. In human keratinocytes, VID400 stabilized levels of endogenously produced 1alpha,25(OH)2D3, and thereby strongly amplified and prolonged expression of CYP24, a surrogate marker of hormonal function. In parallel, antiproliferative activity showed up at 100-fold or more lower concentrations of 1alpha,25(OH)2D3. This data suggests that CYP24 inhibitors could become attractive drugs in antiproliferative therapy, used as single entities to increase or extend endogenous hormone function or in combination with low doses of potent analogs. Moreover, we used selective inhibitors as valuable tools to (a) elucidate regulatory mechanisms of vitamin D synthesis and metabolism, (b) determine intrinsic activities of the otherwise highly transient vitamin D metabolites and (c) model the active sites of CYP24 and CYP27B.

Animals↗

[Serum vitamin A determinations and their value in determining vitamin A status].

As demonstrated in the literature on vitamin A metabolism and homeostasis of retinol in serum, the concentration of retinol in serum is regulated very exactly if the liver stores are within the physiological range (20-300 micrograms/g liver). Therefore, the serum level indicates the status of vitamin A storage only if there is an extreme depletion or overconsumption of vitamin A. At marginal depletion, however, there is damage to peripheral tissue before changes in the vitamin A level in serum occur. At the beginning of hypervitaminosis A, changes in the level of vitamin A in serum also occur later. Therefore, the determination of vitamin A in serum gives no information on the adequacy of liver reserves for judging the necessity of a substitution.

Humans↗

A morphometric investigation of the duodenal mucosa of normal, vitamin D-deficient, and vitamin D-replete rats.

Light and electron microscopy were utilized to determine differences in morphology and size in duodenal villi and microvilli from normal, vitamin D-deficient, and vitamin D-replete rats. An increase in villus diameter and surface area was observed in vitamin D-deficient rats. Administration of vitamin D reversed the increase in diameter but the height of villi increased resulting in longer, thinner villi without a significant change in surface area. A decrease in microvillus surface area seen in vitamin D-deficient animals was reversed by the administration of vitamin D.

Animals↗

The effect of vitamin D status on the severity of bone disease and on the other features of primary hyperparathyroidism (pHPT) in a vitamin D deficient region.

A clear relationship between vitamin D status and the clinical indices of primary hyperparathyroidism (pHPT) severity has not been convincingly established. We proposed that such a relationship might exist, in so far as vitamin D deficiency could contribute to the severity of metabolic bone disease and promote the growth of the parathyroid tumor. Accordingly, we undertook a retrospective study and analyzed the clinical, biochemical, radiological and histopathological findings in a group of 49 patients who underwent parathyroidectomy at our center. Patients who had skeletal X-rays were grouped, according to their X-ray findings, in group A (19 patients; 45%) if they had severe bone changes, or group B (23 patients; 55%) if they had mild or no bone changes. Patients were also stratified according to their 25-hydroxyvitamin D (25-OHD) levels in tertiles. The 2 groups were compared using Fisher's exact test or analysis of variance as appropriate. Group A patients were younger (p=0.001), had more musculoskeletal symptoms (p=0.0003), and complained more frequently of fatigue (p=0.02). They had higher alkaline phosphatase (AP; p=0.0002), PTH index (p=0.0007), and serum Ca level (p=0.006). There were more patients from the lower and middle vitamin D tertiles and fewer patients from the upper vitamin D tertile in group A (p=0.02). Post-operative severe hypo-calcemia was more prevalent in group A patients (p<0.0001). Resected parathyroid tumors were larger in size in group A patients (p=0.01), and weighed more (p=0.01). There was a positive correlation between the weight of the parathyroid tumor and the PTH index (p=0.002), and AP level (p=0.0007). We concluded that vitamin D deficiency is a contributing factor to both the severity of bone disease and the high activity of parathyroid tumors seen in many patients with pHPT in vitamin D deficient regions.

Adenoma↗

Vitamin K-dependent carboxylase: effect of detergent concentrations, vitamin K status, and added protein precursors on activity.

Activity of the rat liver microsomal vitamin K-dependent carboxylase has been studied at various concentrations of detergent. The activity which could be solubilized by 0.25% Triton X-100 was low but could be greatly increased if vitamin K-deficient rats were given vitamin K a few minutes before they were killed. At higher concentrations of Triton, more activity was solubilized and this effect was not seen. In vitro carboxylation of endogenous microsomal proteins was decreased by 80-90% if vitamin K was administered 1 min before rats were killed, but the amount of assayable prothrombin precursor was decreased by only 20%. Decarboxylated vitamin K-dependent rat plasma proteins were not substrates for the carboxylase and did not influence peptide carboxylase activity significantly. Purified microsomal prothrombin precursors did, however, stimulate carboxylation of peptide substrate and were used as a substrate for the carboxylase in a preparation from precursor depleted vitamin K-deficient rats.

Animals↗

Absorption and metabolism of vitamin K in Swiss 3T3 mouse fibroblasts--a model system for study of vitamin K absorption and metabolism.

The vitamin K cycle previously described in liver has been demonstrated in Swiss 3T3 mouse fibroblasts. Vitamin K epoxide and gamma-carboxyglutamic acid were isolated from the cells and chemically characterized. Menaquinone (MK4) is also metabolized to its epoxide and vitamin K epoxide is reduced to vitamin K in these cells. Thus Swiss 3T3 mouse fibroblasts provide a useful model system for the study of vitamin K metabolism. Possible functions of the vitamin K-dependent protein(s) in fibroblasts are discussed.

1-Carboxyglutamic Acid↗