Physiological Doses Of Vitamin Research Articles

Vitamin D for the older patient: from hype to hope?

The review critically appraises the most recent and important meta-analyses that have assessed the effect of vitamin D supplementation on bone health in the older population. Vitamin D status is generally lower in study participants with bone wasting. However, studies on the effects of vitamin D supplementation on bone health, summarized in different meta-analyses, have provided conflicting results, likely because of the heterogeneity between studies. Interventional studies performed using more physiological doses of vitamin D (i.e. avoiding very large, nonphysiological doses) or in study participants with low vitamin D status have provided more beneficial effects on bone health. Meta-analyses assessing the impact of vitamin D in the treatment of osteoporosis are heterogeneous in their conception or their results and sometimes have included inappropriate studies to answer the useful research question for the clinician, making the interpretation and the clinical use of these conflicting meta-analyses quite difficult.

Nutritional intervention and efficacy analysis of children with biliary atresia after Kasai portoenterostomy

Background: Biliary atresia (BA) is the most common cause of cholestatic cirrhosis in children, and liver transplantation (LT) is the sole treatment for this disease. However, a young age and light weight increase the difficulty and risk of LT. Currently, Kasai portoenterostomy (KPE) is the preferred treatment for children with BA to buy time while waiting for a donor liver to become available. The pretransplant nutritional status is the key factor determining post-surgery quality of survival. Therefore, in this study, we followed 40 children with BA who survived with autologous livers after KPE from 2010 to 2017. Individualized nutritional guidance was given, and the post-KPE nutritional status of the children and the jaundice clearance rate were evaluated to better formulate follow-up and nutritional intervention strategies. Methods: The multidisciplinary team (MDT) carried out regular physical examinations of the children after KPE and supplemented them with a physiological dose of vitamin D (400–800 IU). In addition to feeding guidance, children with malnutrition were given medium-chain triglyceride (MCT)-enriched nutritional formula milk. The children’s body weights, body lengths, head circumferences, liver functions, bilirubin levels and plasma vitamin A, D and E levels were measured. The Z-score of physique and the percentiles were calculated using the anthropometric calculator of the WHO Anthro software, and descriptive statistics were evaluated. An independent-samples t-test was used to compare pre- and post-KPE indicators and vitamins. Results: A total of 40 children were included in the study. Their jaundice clearance rate was 56% within 3 months after KPE. Among them, 25 children had good compliance and were followed up at least twice. The patient ages at the last follow-up were 13.38±21.70 months. The male-to-female ratio was 24:16. The mean Z-score and percentiles of body weight and body length/height at the last follow-up for the 40 children were weight for age (WFA) (−1.49±1.54, 26.53±25.91) and length for age (LFA) (−1.39±1.16, 18.93±18.96, respectively). A total of 17.5% (7/40) of the children were emaciated, and 22.5% (9/40) had a short stature. The vitamin A, D and E levels were 0.99±0.29 µmol/L (marginal level), 34.12±16.71 µmol/L and 12.82±1.53 µg/mL, respectively, which did not differ compared to those of children of the same ages from the outpatient children’s health clinic. The prealbumin level was 150.82±47.48 mg/L (lower than the normal level), and the albumin level was 40.67±4.76 g/L (normal range). Conclusions: The jaundice clearance rate was 56% (14/25) for this group of children with BA within 3 months after KPE. At the last follow-up (13.38±21.70 months), the emaciation rate was approximately 17.5% (7/40), and the short stature rate was 22.5% (9/40), which reflected more prominent long-term malnutrition among the BA children. Multidisciplinary cooperation is very important for long-term nutrition management of BA children after KPE.

Vitamin D and inflammation

Several studies found an inverse relationship between 25-hydroxyvitamin D [25(OH)D] and markers of inflammation. A controversy exists as to whether vitamin D lowers inflammation or whether inflammation lowers 25(OH)D concentrations. Certainly 25(OH)D concentrations fall after major surgery. However, is this due to inflammation lowering 25(OH)D or is 25(OH)D being metabolically cleared by the body to quell inflammation. We searched the literature and found 39 randomized controlled trials (RCT) of vitamin D and markers of inflammation. Seventeen found significantly reduced inflammatory markers, 19 did not, one was mixed and one showed adverse results. With few exceptions, studies in normal subjects, obesity, type 2 diabetics, and stable cardiovascular disease did not find significant beneficial effects. However, we found that 6 out of 7 RCTS of vitamin D3 in highly inflammatory conditions (acute infantile congestive heart failure, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, SLE, active TB and evolving myocardial infarction) found significant reductions. We found baseline and final 25(OH)D predicted RCTs with significant reduction in inflammatory markers. Vitamin D tends to modestly lower markers of inflammation in highly inflammatory conditions, when baseline 25(OH)D levels were low and when achieved 25(OH)D levels were higher. Future inquiries should: recruit subjects with low baseline 25(OH)D levels, subjects with elevated markers of inflammation, subjects with inflammatory conditions, achieve adequate final 25(OH)D levels, and use physiological doses of vitamin D. We attempted to identify all extant randomized controlled trials (RCTs) of vitamin D that used inflammatory markers as primary or secondary endpoints.

The Effects of Supraphysiologic Doses of Vitamin D3 in Conjunction With Teriparatide on Bone Mineral Density in Two Postmenopausal Females With Severe Osteoporosis

Teriparatide was approved by the FDA in 2002 for the treatment of osteoporosis in postmenopausal women who are at high risk for fractures. Previous studies involving the use of teriparatide in conjunction with vitamin D and calcium supplementation have suggested that sufficient vitamin D levels may not be a requirement to achieve an effective response to teriparatide. We present a case of two postmenopausal females with severe osteoporosis who were treated with teriparatide along with calcium and supraphysiologic doses of vitamin D, as illustrated by an increase from their baseline serum 25-hydroxyvitamin D concentrations. Both patients experienced an increase in bone mineral density that was significantly higher than what has been seen in prior studies of teriparatide administration in conjunction with physiologic doses of vitamin D. These findings suggest that administering supraphysiologic doses of vitamin D may in fact potentiate the effects of teriparatide in postmenopausal females with osteoporosis, resulting in larger increases in bone mineral density than would otherwise be expected. doi:10.4021/jem104 w

The Effects of Supraphysiologic Doses of Vitamin D3 in Conjunction With Teriparatide on Bone Mineral Density in Two Postmenopausal Females With Severe Osteoporosis

Teriparatide was approved by the FDA in 2002 for the treatment of osteoporosis in postmenopausal women who are at high risk for fractures. Previous studies involving the use of teriparatide in conjunction with vitamin D and calcium supplementation have suggested that sufficient vitamin D levels may not be a requirement to achieve an effective response to teriparatide. We present a case of two postmenopausal females with severe osteoporosis who were treated with teriparatide along with calcium and supraphysiologic doses of vitamin D, as illustrated by an increase from their baseline serum 25-hydroxyvitamin D concentrations. Both patients experienced an increase in bone mineral density that was significantly higher than what has been seen in prior studies of teriparatide administration in conjunction with physiologic doses of vitamin D. These findings suggest that administering supraphysiologic doses of vitamin D may in fact potentiate the effects of teriparatide in postmenopausal females with osteoporosis, resulting in larger increases in bone mineral density than would otherwise be expected. J Endocrinol Metab. 2012;2(3):139-144 doi: https://doi.org/10.4021/jem104w

Vitamin E supplementation enhances growth and condition of nestling barn swallows (Hirundo rustica)

To optimize fitness, organisms may have to trade the number and quality of individual offspring against their own condition and survival. Limiting micronutrients such as antioxidants may be crucial to this trade-off. We investigated whether vitamin E, a major antioxidant in the diet of vertebrates, is limiting to barn swallow (Hirundo rustica) nestlings. We manipulated brood size to alter the intensity of sib–sib competition and supplemented nestlings with two different physiological doses of vitamin E while establishing a control group. Treatment effects were measured on body mass and size, feather growth, T cell-mediated immune response and hematocrit. Supplementation with vitamin E at intermediate physiological doses improved nestling mass and condition and feather growth, whereas higher physiological doses did not enhance offspring quality compared to a control treatment. The positive effects of vitamin E on body mass and condition were only detectable from days 6 to 10 when maximum growth rate is attained. Experimental enlargement of broods reduced body mass and size and T cell-mediated immune response only during the late nestling period. The effect of vitamin E supplementation did not depend on brood size manipulation, as revealed by the nonsignificant statistical interaction. This result contradicts the hypothesis that availability of vitamin E depends on intrabrood competition and instead suggests that it depends on concentration of vitamin E in the insect prey of swallows. Thus, antioxidants may be available in limited amounts to barn swallow nestlings and such limitation affects growth. In addition, present results confirm that barn swallow parents trade progeny number against growth and immunity of individual offspring.

Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete

Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation.

Effect Of Alendronate Treatment On Bone Mineral Density In Male Patients With Osteoporosis

To assess the efficacy of alendronate therapy on bone mineral density (BMD) at the lumbar spine and hip in men with osteoporosis. Medical records of male patients with osteoporosis, who had undergone follow-up in the Endocrinology Clinic at the National Naval Medical Center, were reviewed, and nine patients treated with alendronate for at least 1 year were identified. Patients were excluded from analysis if they had evidence of osteomalacia or if baseline and follow-up BMD results on the same dual-energy x-ray absorptiometry (DEXA) densitometer, at least 10 months apart, were not available. DEXA BMD results at the lumbar spine and hip, before and after at least 10 months of alendronate treatment, were analyzed for significant differences. Patients were also receiving calcium supplementation (1,000 to 1,500 mg/day), and all but one patient received vitamin D (400 to 800 U/day). Lumbar spine BMD increased by 6.4 +/- 1.8% per year with alendronate treatment (P = 0.008). A mean absolute gain of 0.052 +/- 0.010 g/cm 2 (P = 0.005) in lumbar spine BMD was noted for the entire study group (N = 9), after a mean duration of treatment of 14 +/- 1 months. The mean lumbar spine BMD Z score improved by 0.40 +/- 0.09 (P = 0.002) with alendronate therapy. The femoral neck BMD also increased by 4.5 +/- 1.4% per year with alendronate treatment (P = 0.013). The mean absolute gain in femoral neck BMD was 0.028 +/- 0.009 g/cm 2 (P = 0.013) for the study group (N = 9) after 14 +/- 1 months of therapy. The mean femoral neck BMD Z score improved 0.30 +/- 0.08 (P = 0.005) with treatment. BMD gains at the greater trochanter of 3.2 +/- 1.5% per year (P = 0.067) and at Ward's triangle of 9.1 +/- 4.2% per year (P = 0.061) were not statistically significant. Two patients discontinued alendronate treatment after 1 year because of epigastric or retrosternal pain. Oral alendronate treatment, given in combination with calcium supplementation and physiologic doses of vitamin D, resulted in significant improvements in lumbar spine and femoral neck BMD after a 14-month period in this small group of men with osteoporosis. Although controlled, prospective trials involving larger numbers of male patients with fracture incidence data are needed before definitive conclusions can be made, alendronate treatment seems to be effective in improving BMD in men with osteoporosis, similar to its efficacy in women.

Is there a differential response to alfacalcidol and vitamin D in the treatment of osteoporosis?

: There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)2D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 micro;g twice daily improved calcium absorption, decreased serum PTH, and reduced alkaline phosphatase, whereas vitamin D2 500-1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of elderly women with vertebral osteoporosis.

Is there a differential response to alfacalcidol and vitamin D in the treatment of osteoporosis?

There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)2D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 μg twice daily improved calcium absorption, decreased serum PTH, and reduced alkaline phosphatase, whereas vitamin D2 500–1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of elderly women with vertebral osteoporosis.

Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus.

Diabetic hyperglycemia promotes sorbitol production from glucose via aldose reductase. Since the intracellular accumulation of sorbitol, or its sequelae, are postulated to contribute to the progression of chronic diabetic complications, aldose reductase inhibitors (ARI) offer therapeutic promise. Others have shown that vitamin C at pharmacologic doses decreases erythrocyte (RBC) sorbitol. We examined whether smaller, physiologic doses of vitamin C were also effective in individuals with insulin-dependent diabetes mellitus (IDDM) and whether vitamin C was an ARI in vitro. Vitamin C supplements (100 or 600 mg) were taken daily for 58 days by young adults with IDDM and nondiabetic adults in an otherwise free-living design. Diabetic control was monitored by fasting plasma glucose, glycosylated hemoglobin, and glycosuria and was moderate to poor throughout the study. RBC sorbitol was measured at baseline and again at 30 and 58 days. Three-day dietary records and 24-hour urine collections were performed for each sampling day. RBC sorbitol levels were significantly elevated in IDDMs, on average doubled, despite their more than adequate dietary intakes of vitamin C and normal plasma concentrations. Vitamin C supplementation at either dose normalized the RBC sorbitol in IDDMs within 30 days. This correction of sorbitol accumulation was independent of changes in diabetic control. Furthermore, our in vitro studies show that ascorbic acid inhibited aldose reductase activity. Vitamin C supplementation is effective in reducing sorbitol accumulation in the erythrocytes of diabetics. Given its tissue distribution and low toxicity, we suggest a superiority for vitamin C over pharmaceutic ARIs.

Osteopetrorickets

Rickets is a common and paradoxical feature of infantile malignant osteopetrosis and results from the inability of osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. Despite a markedly positive total body calcium balance, rickets arises when the serum calcium x phosphorus product is insufficient to mineralize newly formed chondroid and osteoid. In five children with malignant infantile osteopetrosis, there were clinical, radiographic, biochemical, and histologic findings of rickets. Characteristic biochemical abnormalities included hypocalcemia, hypophosphatemia, and elevated levels of serum acid phosphatase, alkaline phosphatase, c-terminal parathyroid hormone, and 1,25-dihydroxyvitamin D. The urinary calcium/creatinine ratio was markedly depressed. The serum calcium x phosphorus product was below 30 in all children at the time the rickets was diagnosed, and above 40 by the time the rickets had resolved. Baseline bone density measurements were markedly elevated in all children (> 5 standard deviation above normal) and showed even significant increases (> 7 SD) when the rickets was treated with vitamin D and calcium. The children showed marked clinical improvement, decreased lethargy, increase in mobility and activity, and stimulation of appetite, without any additional adverse hematologic or neurologic effects. The rickets was reversible in all children: in one by HLA-identical sibling bone marrow transplantation and in four by physiologic doses of vitamin D and calcium. The parathyroid and renal responses to hypocalcemia were appropriate, but glucocorticoids, used in treating the hematologic complications of the disease, may have blunted the intestinal response to maximal vitamin D stimulation. This latter blockade can be overcome by increasing dietary calcium. By liberalizing rather than by restricting calcium and phosphorus intake, hypocalcemia can be minimized, phosphorus metabolism can be improved, and rickets can be cured.

Vitamin D metabolism in children with malabsorption syndrome

In 16 children with malabsorption syndrome, out of which 5 had impaired lipid absorption or diarrhoea, and in 14 children in the control group the concentrations of vitamin D and 25 OH D3 were determined after oral administration of vitamin D in dose of 1200 U/kg.b.wt. or 12000 U/kg.b.wt. No decrease in initial 25 OH D3 concentrations was noted in children with malabsorption syndrome (40,5 +/- 0,7 ng/ml) in comparison with the control group (40,0 +/- 0,4 ng/ml). In children with impaired lipid absorption and diarrhoea the 25 OH D3 concentration was 33,6 +/- 2,4 ng/ml. After oral administration of vitamin D in small doses no differences were noted in the increase in vitamin D and 25 OH D3 concentrations in children with malabsorption syndrome or the control group. After administration of vitamin D in the dose 10 times higher no difference in the increase in vitamin D concentration was noted in children with malabsorption syndrome and the control group. However the increase in 25 OH D3 concentration in children with malabsorption syndrome was 49,8 +/- 1,2 ng/ml and 145,0 +/- 3,5 ng/ml in the control group. In the children with impaired lipid absorption and diarrhoea decreased vitamin D and 25 OH D3 concentrations were noted. This means that physiological doses of vitamin D in children with malabsorption syndrome are sufficient to supply vitamin D. Diarrhoea and impaired lipid absorption however, are indications for stimulation of skin synthesis of vitamin D.

Studies on the mode of action of calciferol. X. 24-Nor-25-hydroxyvitamin D 3, an analog of 25-hydroxyvitamin D 3 having “anti-vitamin” activity

24-Nor-25-hydroxyvitamin D 3, an analog of 25-hydroxyvitamin D 3, has been chemically synthesized in six steps. This steroid was tested in chicks, in vivo , for its ability to generate the classic vitamin D mediated responses of stimulation of intestinal calcium transport and bone calcium mobilization. Although the 24-nor-25-OH-vitamin D 3 itself exhibited no biological activity in these assays, the analog was found to inhibit the normal responses produced by a physiological dose of vitamin D 3. These results suggest that 24-nor-25-OH-vitamin D 3 may satisfy certain requirements expected of a calciferol “anti-vitamin.”

Effect of mixed micellar lipid on the absorption of cholesterol and vitamin D3 into lymph.

The absorption of endogenous cholesterol, labeled with tracer doses of cholesterol (14)C or cholesterol-(3)H and of near physiological doses of vitamin D(3)-(3)H was studied in rats with cannulated intestinal lymphatics. The effects of administering mixed micellar solutions of fatty acid, monoglyceride, and bile salt on the absorption of these labeled sterols was determined. It was observed that the specific activity of free cholesterol and the amounts of vitamin D(3) appearing in lymph were significantly increased during the intraduodenal administration of mixed micellar solutions of either linoleic or palmitic acid, in contrast to control rats receiving a micellar solution of taurocholate. These increases were related linearly to the lymph triglyceride level. In addition it was observed that when the linoleic acid solution was administered there was a more marked increase in the ratio of the specific activities of free and esterified cholesterol in lymph than with either the palmitic acid or taurocholate solutions. Additional studies in rats with intact lymphatics showed that the uptake of labeled cholesterol and vitamin D(3) from the intestinal lumen into the wall was similar whether the sterols were administered in taurocholate or in mixed micellar solution. These findings suggest that mixed micellar lipid increased the rate of appearance of labeled free cholesterol and vitamin D(3) in lymph by enhancing their transport out of the intestinal mucosa, rather than by an effect on uptake.

The Antagonistic Effect of Vitamin a on Vitamin K in the Germfree Rat.

Survival time of the germfree rat on a diet deficient in vitamin K is not affected by physiological doses of vitamin A. However, excess doses of vitamin A may result in systemic antagonism to vitamin K.

The site of absorption and tissue distribution of orally administered 56Co-labelled vitamin B12 in the rat.

BOOTH and Mollin (1956), using vitamin B,, labelled with 56C~, have shown that when normal human subjects are given physiological doses of vitamin B,,, which arc absorbed through the agency of intrinsic factor, the amount that appears in the plasma is very small. Furthermore, tlic appearance of radioactive material in the plasma is dclaycd until 3 hours or morc after the administration of the dose and peak concentrations do not appear for 8 to 12 hours. These observations suggest cithcr that vitamin B,, is absorbed low down in the intestine or that the passage of thc vitamin through the intestinal wall is a slow and complicated process. They also indicate that the absorbed B,, is probably cleared rapidly from the plasma into the tissues. Watson and Florey (195s) and Nieweg, Areiids, Manderna and Castle (1956) have shown that the rat possesses an intrinsic-factor mechanism for the absorption of vitamin B,, which is similar to that found in man. Thcir work suggested that this animal might be suitable for investigating the mechanism of absorption of small doses of labelled B12. We have therefore studied the uptakc of radioactive B,, by the intestine of thc rat, its transfer to the blood stream and subsequent distribution in the tissues. The purpose of this paper is to report the results of our observations.