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1.  Hypersegmented neutrophils and reversible hyperpigmentation in vitamin B12 deficiency in Ghana 
BMJ Case Reports  2009;2009:bcr08.2008.0686.
The present report concerns three cases of vitamin B12 deficiency in Ghana. One case presented in the expected textbook manner with neurological signs, anaemia and a low serum vitamin B12 level, whereas another presented with anaemia and hyperpigmentation, but a high serum vitamin B12 level. Both responded well to treatment with vitamin B12. It is suggested from the literature that the high serum vitamin B12 may have been the result of high intrinsic factor antibodies. The third patient presented with haemolytic anaemia with depression, and was managed as such initially. She responded well, with a normalisation of haemoglobin levels. Persisting vague neurological symptoms lead to a check of serum vitamin B12, which was found to be low. Her symptoms cleared with vitamin B12 treatment. The need for a pragmatic approach in diagnosing vitamin B12 deficiency is stressed.
doi:10.1136/bcr.08.2008.0686
PMCID: PMC3029090  PMID: 21918662
2.  Correction of vitamin D deficiency in critically ill patients - VITdAL@ICU study protocol of a double-blind, placebo-controlled randomized clinical trial 
Background
Vitamin D deficiency is associated with multiple adverse health outcomes including increased morbidity and mortality in the general population and in critically ill patients. However, no randomized controlled trial has evaluated so far whether treatment with sufficiently large doses of vitamin D can improve clinical outcome of patients in an intensive care setting.
Methods/design
The VITdAL@ICU trial is an investigator-initiated, non-commercial, double-blind, placebo-controlled randomized clinical trial. This study compares high-dose oral cholecalciferol (vitamin D3) versus placebo treatment in a mixed population of 480 critically ill patients with low 25-hydroxyvitamin-D levels at study enrollment (≤ 20ng/ml). Following an initial loading dose of 540,000 IU of vitamin D3, patients receive 90,000 IU of vitamin D3 on a monthly basis for 5 months. The study is designed to compare clinical outcome in the two study arms with the primary endpoint being length of hospital stay. Secondary endpoints include among others length of ICU stay, the percentage of patients with 25(OH)D levels > 30 ng/ml at day 7, ICU and hospital mortality and duration of mechanical ventilation. We describe here the VITdAL@ICU study protocol for the primary report.
Discussion
This trial is designed to evaluate whether high-dose vitamin D3 is able to improve morbidity and mortality in a mixed population of adult critically ill patients and correct vitamin D deficiency safely.
Trial registration
ClinicalTrials: NCT01130181
doi:10.1186/1472-6823-12-27
PMCID: PMC3534412  PMID: 23134762
Critical Illness; Vitamin D deficiency; Cholecalciferol; Vitamin D; Critical care; Intensive care; Vitamin D3
3.  Treatment of osteomalacia associated with primary biliary cirrhosis with parenteral vitamin D2 or oral 25-hydroxyvitamin D3. 
Gut  1979;20(2):133-136.
The histological and biochemical response of osteomalacia has been studied in four patients with primary biliary cirrhosis, who were treated with oral 25-hydroxyvitamin D3, 50 microgram daily, or intramuscular vitamin D2, 150,000 units once weekly, for five to 12 months. All patients showed complete histological healing of osteomalacia, despite rapidly deteriorating liver function in three. Plasma 25-hydroxyvitamin D concentrations were low in all patients before treatment, but became normal during either vitamin therapy. Serum calcium and phosphate levels, and urinary calcium excretion were not always reliable in predicting the histological response to treatment. Serum alkaline phosphatase activity decreased in all patients during vitamin D therapy. We conclude that both high-dose parenteral vitamin D2 and oral 25-hydroxyvitamin D3 may be effective in healing osteomalacia associated with primary biliary cirrhosis. Measurement of plasma 25-hydroxyvitamin D levels during vitamin D therapy provides useful information about 25-hydroxylation of the parent vitamin and intestinal absorption of orally administered 25-hydroxyvitamin D3.
PMCID: PMC1419456  PMID: 311747
4.  A Case of Vitamin D Deficiency without Elevation of Serum Alkaline Phosphatase in a Carrier of Hypophosphatasia 
Elevated serum alkaline phosphatase (ALP) is a screening marker for the diagnosis of vitamin D deficiency, which may fail to be diagnosed if serum ALP is not elevated. Here, we describe a case of vitamin D deficiency without elevation of serum ALP. A 1-year-old Japanese girl was referred to our hospital for the evaluation of genu varum. Her serum intact PTH level was elevated, while her serum ALP level was normal. Furthermore, her serum 25-hydroxyvitamin D level was reduced, and her urine phosphoethanolamine (PEA) level was mildly elevated. ALPL gene analysis revealed she was a heterozygous carrier of hypophosphatasia (c.1559delT). Serum intact PTH and urine PEA evaluations were helpful for diagnosing vitamin D deficiency and hypophosphatasia carrier status, respectively. Therefore, the possibility of vitamin D deficiency without elevation of serum ALP should be considered.
doi:10.1292/cpe.22.73
PMCID: PMC3809733  PMID: 24170964
vitamin D deficiency; hypophosphatasia; ALPL; intact PTH; phosphoethanolamine
5.  The JUPITER lipid lowering trial and vitamin D 
Dermato-endocrinology  2010;2(2):50-54.
There is growing evidence that vitamin D deficiency significantly increases the risk of adverse cardiovascular events and that a vitamin D status representing sufficiency or optimum is protective. Unfortunately, in clinical trials that address interventions for reducing risk of adverse cardiovascular events, vitamin D status is not generally measured. Failure to do this has now assumed greater importance with the report of a study that found rosuvastatin at doses at the level used in a recent large randomized lipid lowering trial (JUPITER) had a large and significant impact on vitamin D levels as measured by the metabolite 25-hydroxyvitamin D. The statin alone appears to have increased this marker such that the participants on average went from deficient to sufficient in two months. The difference in cardiovascular risk between those deficient and sufficient in vitamin D in observational studies was similar to the risk reduction found in JUPITER. Thus it appears that this pleiotropic effect of rosuvastatin may be responsible for part of its unusual effectiveness in reducing the risk of various cardiovascular endpoints found in JUPITER and calls into question the interpretation based only on LDL cholesterol and CRP changes. In addition, vitamin D status is a cardiovascular risk factor which up until now has not been considered in adjusting study results or in multivariate analysis, and even statistical analysis using only baseline values may be inadequate.
doi:10.4161/derm.2.2.13235
PMCID: PMC3081676  PMID: 21547097
vitamin D; rosuvastatin; cardiovascular disease; JUPITER; heart disease; statins
6.  Dose response to vitamin D supplementation among postmenopausal African American women123 
Background
Reports on the dose response to vitamin D are conflicting, and most data were derived from white men and women.
Objective
The objective was to determine the response of serum 25-hydroxyvitamin D [25(OH)D] to oral vitamin D3 supplementation in an African American population.
Design
Healthy black postmenopausal women (n = 208) participated in a vitamin D3 supplementation trial for a period of 3 y. Analyses were done in the vitamin D supplementation arm (n = 104) to quantify the response in serum 25-hydroxyvitamin D concentrations at a steady state vitamin D input. The participants received 20 μg/d (800 IU) oral vitamin D3 for the initial 2 y and 50 μg/d (2000 IU) for the third year.
Results
Supplementation with 20 μg/d (800 IU/d) vitamin D3 raised the mean serum 25(OH)D concentration from a baseline of 46.9 ± 20.6 nmol/L to 71.4 ± 21.5 nmol/L at 3 mo. The mean (± SD) concentration of serum 25(OH)D was 87.3 ± 27.0 nmol/L 3 mo after supplementation increased to 50 μg/d (2000 IU/d). All participants achieved a serum 25(OH)D concentration >35 nmol/L, 95% achieved a concentration >50 nmol/L, but only 60% achieved a concentration >75 nmol/L. All patients had concentrations <153 nmol/L. On the basis of our findings, an algorithm for prescribing vitamin D so that patients reach optimal serum concentrations was developed. The algorithm suggests a dose of 70 μg (2800 IU/d) for those with a concentration >45 nmol/L and a dose of 100 μg (4000 IU/d) for those with a concentration <45 nmol/L.
Conclusions
Supplementation with 50 μg/d (2000 IU/d) oral vitamin D3 is sufficient to raise serum 25-hydroxyvitamin D concentrations to >50 nmol/L in almost all postmenopausal African American women. However, higher doses were needed to achieve concentrations >75 nmol/L in many women in this population.
PMCID: PMC2581841  PMID: 18065583
Ethnicity; vitamin D; 25-hydroxyvitamin D; osteoporosis; vitamin D deficiency; African Americans
7.  A possible correlation between vitamin D deficiency and loss of smell: 2 case reports 
Journal of Chiropractic Medicine  2011;10(4):310-315.
Objective
The purpose of this report is to present 2 cases of diminished olfaction that improved with increasing serum levels of vitamin D3.
Clinical Features
Both patients were under the care of medical and chiropractic physicians for various complaints. A 47-year-old hyposmic woman was diagnosed with vitamin D deficiency who incidentally noticed a progressive return of her sense of smell while taking vitamin D supplements as prescribed by her medical doctor. A 34-year-old anosmic woman noticed a direct relationship with her ability to smell and vitamin D3 supplementation.
Intervention and Outcome
Treatment for the first patient consisted of vitamin D supplementation of 10 000 IU a day. Her serum D3 levels increased substantially over a period of 8 months, at which time she reported a marked improvement in her sense of smell. The second patient was prescribed 50 000 IU of vitamin D a week; and she reported an increased ability to smell, although only the strongest of odors.
Conclusion
A link between hypovitaminosis D and a diminished sense of smell was noted in these 2 individuals.
doi:10.1016/j.jcm.2011.06.006
PMCID: PMC3315864  PMID: 22654691
Vitamin D; Vitamin D deficiency; Olfaction disorders; Smell; Odors; Chiropractic
8.  First Trimester Vitamin D, Vitamin D Binding Protein, and Subsequent Preeclampsia 
Hypertension  2010;56(4):758-763.
Prior studies report an association between vitamin D deficiency and hypertension, including the pregnancy-specific disorder, preeclampsia. Circulating vitamin D is almost entirely bound to vitamin D binding protein, which increases 2-fold during pregnancy, but previous studies have not examined vitamin D binding protein or free vitamin D levels. We performed a nested case-control study within the Massachusetts General Hospital Obstetrical Maternal Study (MOMS), measuring first trimester total 25-hydroxyvitamin D and vitamin D binding protein, and calculating free 25-hydroxyvitamin D levels. We compared these levels from pregnancies complicated by subsequent preeclampsia (cases, n=39) with those from normotensive pregnancies (controls, n=131). First trimester total 25-hydroxyvitamin D levels were similar in cases and controls (27.4 ±1.9 ng/ml vs. 28.8±0.80 ng/ml, p=0.435). Despite an association between higher first trimester blood pressures and subsequent preeclampsia, first trimester total 25-hydroxyvitamin D was not associated with first trimester systolic (r=0.11, p=0.16) or diastolic blood pressures (r=0.03, p=0.72). Although there was a trend toward increased risk of preeclampsia with 25-hydroxyvitamin D levels less than 15 ng/ml (OR 2.5, 95% CI 0.89-6.9), this was attenuated after adjustment for body mass index and other covariates (OR 1.35 95% CI 0.40-4.5). First trimester vitamin D binding protein and free 25-hydroxyvitamin D levels were similar in cases and controls and were not associated with first trimester blood pressures. These data suggest that first trimester total and free 25-hydroxyvitamin D levels are not independently associated with first trimester blood pressure or subsequent preeclampsia.
doi:10.1161/HYPERTENSIONAHA.110.158238
PMCID: PMC3775612  PMID: 20733087
vitamin D; vitamin D Binding Protein; preeclampsia; pregnancy
9.  Vitamin D Deficiency in Adults: When to Test and How to Treat 
Mayo Clinic Proceedings  2010;85(8):752-758.
Recent evidence for the nonskeletal effects of vitamin D, coupled with recognition that vitamin D deficiency is common, has revived interest in this hormone. Vitamin D is produced by skin exposed to ultraviolet B radiation or obtained from dietary sources, including supplements. Persons commonly at risk for vitamin D deficiency include those with inadequate sun exposure, limited oral intake, or impaired intestinal absorption. Vitamin D adequacy is best determined by measurement of the 25-hydroxyvitamin D concentration in the blood. Average daily vitamin D intake in the population at large and current dietary reference intake values are often inadequate to maintain optimal vitamin D levels. Clinicians may recommend supplementation but be unsure how to choose the optimal dose and type of vitamin D and how to use testing to monitor therapy. This review outlines strategies to prevent, diagnose, and treat vitamin D deficiency in adults.
doi:10.4065/mcp.2010.0138
PMCID: PMC2912737  PMID: 20675513
10.  A case of metastatic leptomeningeal carcinomatosis from early gastric carcinoma 
Metastatic leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of solid carcinomas. The most common causes of leptomeningeal carcinomatosis are breast cancer, lung cancer and malignant melanoma. Leptomeningeal carcinomatosis associated with gastric cancer, especially in its early stages, is exceedingly rare. Its presenting symptoms include headache, nauseaand seizures. In this report, we describe a case of leptomeningeal metastasis that presented with early-stage gastric cancer. A 67-year-old woman with a history of early-stage gastric cancer in remission was admitted to our hospital with 3 days of headache and nausea. Her gastric cancer had been treated 29 months prior to presentation by a radical subtotal gastrectomy with a Billroth I anastomosis. She had an uneventful recovery until she was diagnosed with metastases to the left axilla and neck 26 months after surgery. Her presenting symptoms of headache and nausea prompted cytologic examination of the cerebrospinal fluid and measurement of tumor markers, which revealed metastatic leptomeningeal carcinomatosis from her gastric cancer. This report aims to raise awareness of the possibility that even early-stage gastric cancer can lead to leptomeningeal carcinomatosis.
doi:10.1186/1477-7819-10-74
PMCID: PMC3436725  PMID: 22553956
Early gastric cancer; Carcinomatosis; Leptomeningeal; Signet ring cell
11.  Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology 
AIM: To examine the vitamin D status in patients with alcoholic cirrhosis compared to those with primary biliary cirrhosis.
METHODS: Our retrospective case series comprised 89 patients with alcoholic cirrhosis and 34 patients with primary biliary cirrhosis who visited our outpatient clinic in 2005 and underwent a serum vitamin D status assessment.
RESULTS: Among the patients with alcoholic cirrhosis, 85% had serum vitamin D levels below 50 nmol/L and 55% had levels below 25 nmol/L, as compared to 60% and 16% of the patients with primary biliary cirrhosis, respectively (P < 0.001). In both groups, serum vitamin D levels decreased with increasing liver disease severity, as determined by the Child-Pugh score.
CONCLUSION: Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology, with lower levels of vitamin D in alcoholic cirrhosis than in primary biliary cirrhosis.
doi:10.3748/wjg.v17.i7.922
PMCID: PMC3051142  PMID: 21412501
Alcoholic liver cirrhosis; Child-Pugh score; Primary biliary cirrhosis; Vitamin D deficiency
12.  High Dose Vitamin D Therapy for Chronic Pain in Children and Adolescents with Sickle Cell Disease: Results of a Randomized Double Blind Pilot Study 
British journal of haematology  2012;159(2):211-215.
Summary
We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were followed for 6 months after receiving a six-week course of oral high-dose cholecalciferol or placebo. Vitamin D insufficiency and deficiency was present at baseline in 82.5% and 52.5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.
doi:10.1111/bjh.12019
PMCID: PMC3460143  PMID: 22924607
Vitamin D; Chronic Pain; Sickle Cell; Paediatrics; Quality of Life
13.  Vitamin D metabolism in acute and chronic cholestasis 
Gut  1979;20(10):840-847.
To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected 3H vitamin D3 (3HD3) and the subsequent production of 3H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less 3H 25OHD than expected were receiving vitamin D supplements. The urinary tritium (3H) excretion after the injection of 3HD3 correlated with the serum bilirubin. After the injection of 3H 25OHD3 the urinary excretion of 3H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the 3H vitamin D3 injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.
PMCID: PMC1412708  PMID: 230129
14.  Association between neurological and rheumatological manifestations in vitamin D deficiency and vitamin D levels 
Objective: We aimed to investigate the associations between the neurological manifestations of vitamin D deficiency and bone profile as well as the levels of 25-hydroxyvitamin D.
Methodology: We conducted a case series on patients with vitamin D deficiency who were followed up at King Abdulaziz Medical City, Jeddah between January 2010 and December 2011. We collected patients’ demographic data and gathered information on etiological factors for vitamin D deficiency as well as clinical presentations (typical, neurological and rheumatological) and radiological findings. The t-test was used to determine whether there was an association between the neurological manifestations of vitamin D deficiency and vitamin D levels and bone profile.
Results: We enrolled 60 patients with vitamin D deficiency. Of these, 44 (73.3%) had neurological presentations, namely progressive muscle weakness and proximal weakness, which was observed more often than distal weakness. In addition, gait disturbances were observed in 61.7% of all patients with neurological and rheumatological presentations. There was no significant association between neurological and rheumatological manifestations and bone profile or vitamin D levels. We found a significant association between difficulty in walking and the levels of serum calcium and phosphate (P = 0.043 and 0.037, respectively).
Conclusion: Neurological and rheumatologic manifestations of vitamin D deficiency are not associated with 25-hydroxyvitamin D levels or bone profile.
PMCID: PMC3809282  PMID: 24353618
Vitamin D deficiency; Vitamin D; Proximal myopathy; Bone profile
15.  Vitamin D Status and Incidence of Pulmonary Tuberculosis, Opportunistic Infections, and Wasting Among HIV-Infected Tanzanian Adults Initiating Antiretroviral Therapy 
The Journal of Infectious Diseases  2012;207(3):378-385.
Background. Maintaining vitamin D sufficiency may decrease the incidence of pulmonary tuberculosis and other infectious diseases. We present the first prospective study of vitamin D among human immunodeficiency virus (HIV)–infected adults receiving antiretrovirals in sub-Saharan Africa.
Methods. Serum 25-hydroxyvitamin D (25(OH)D) level was assessed at antiretroviral therapy (ART) initiation for 1103 HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania. Participants were prospectively followed at monthly visits at which trained physicians performed a clinical examination and nurses took anthropometric measurements and assessed self-reported symptoms. Cox proportional hazards models estimated hazard ratios (HRs) of morbidity outcomes.
Results. After multivariate adjustment, vitamin D deficiency (defined as a concentration of <20 ng/mL) had a significantly greater association with incident pulmonary tuberculosis, compared with vitamin D sufficiency (HR, 2.89; 95% confidence interval [CI], 1.31–7.41; P = .027), but no association was found for vitamin D insufficiency (defined as a concentration of 20–30 ng/mL; P = .687). Deficiency was also significantly associated with incident oral thrush (HR, 1.96; 95% CI, 1.01–3.81; P = .046), wasting (HR, 3.10; 95% CI, 1.33–7.24; P = .009), and >10% weight loss (HR, 2.10; 95% CI, 1.13–3.91; P = .019). Wasting results were robust to exclusion of individuals experiencing pulmonary tuberculosis. Vitamin D status was not associated with incident malaria, pneumonia, or anemia.
Conclusions. Vitamin D supplementation trials for adults receiving ART appear to be warranted.
doi:10.1093/infdis/jis693
PMCID: PMC3537448  PMID: 23162137
Vitamin D; micronutrient; HIV; tuberculosis; wasting; malaria; pneumonia; morbidity; ART
16.  Severe Hypocalcemia due to Vitamin D Deficiency after Extended Roux-en-Y Gastric Bypass 
Journal of Obesity  2011;2011:141024.
Vitamin D deficiency is a well-known comorbidity of obesity that can be exacerbated after bariatric surgery and can predispose the patient for hypocalcemia. Vitamin D and calcium doses to prevent and treat vitamin D deficiency after weight loss surgery are not well defined. We describe a patient who developed severe hypocalcemia due to vitamin D deficiency 5 years after an extended Roux-en-Y gastric bypass for a type II obesity. No precipitating factors were present and malabsorption induced by the bypass was considered to be the main causative factor. High doses of vitamin D and calcium were needed to reach and maintain normal calcium and vitamin D concentrations. This case emphasises the importance of routine screening for vitamin D deficiency in obese individuals and reflects that while consensus does not exist regarding optimal dosage, vitamin D replacement should be tittered based on calcidiol levels.
doi:10.1155/2011/141024
PMCID: PMC3136099  PMID: 21772998
17.  Congenital rickets caused by maternal vitamin D deficiency 
Paediatrics & Child Health  2002;7(7):455-458.
The cases of four newborn infants with congenital rickets are reported. All infants were native Canadian: three were Cree and one was Inuit. One had a narrow chest and pulmonary hypoplasia, two had clinical and radiological signs of rickets with craniotabes, thickened wrists, and prominent costochondral junctions, and one had perinatal asphyxia and hydrops. All had hypocalcemia, hypophosphatemia and secondary hyperparathyroidism. Serum 25-hydroxyvitamin D levels were low in three of the infants. The four mothers had evidence of vitamin D deficiency. All infants recovered following treatment with 5000 IU oral vitamin D daily.
PMCID: PMC2795674  PMID: 20046322
Congenital rickets; Hyperparathyroidism; Hypocalcemia; 25-hydroxyvitamin D
18.  The prevalence of vitamin D deficiency in iron-deficient and normal children under the age of 24 months 
Blood research  2013;48(1):40-45.
Background
Iron and vitamin D deficiencies cause a variety of health issues in children, which might have long-lasting effects even in asymptomatic cases. The present study sought to elucidate the potential association between iron status and serum vitamin D levels in infants.
Methods
We evaluated 102 infants aged 3-24 months who visited the CHA Bundang Medical Center from August 2010 to July 2011. Questionnaire and laboratory data were collected. The infants were classified into iron deficiency anemia (IDA), iron deficiency (ID), and normal groups according to hemoglobin (Hb) and ferritin levels. They were then classified into vitamin D deficiency (VDD), vitamin D insufficiency (VDI), and vitamin D sufficiency (VDS) groups according to 25-hydroxyvitamin D [25(OH)D] levels.
Results
VDD was present in 67% of IDA, 53% of ID, and 29% of normal subjects. The proportion of breastfed infants was the highest in the IDA (97%) and VDD (96%) groups. The odds ratio for the likelihood of iron-deficient infants to have subnormal vitamin D levels was 4.115. There was a significant correlation between Hb and 25(OH)D levels. Plasma 25(OH)D levels were lower in the winter/spring. Body mass index values were higher in the IDA/ID groups. Iron, age, and season were predictors of 25(OH)D levels.
Conclusion
The prevalence of iron and vitamin D deficiency was high in breastfed infants. There was also a significant association between Hb and 25(OH)D levels in infants. Since all breastfed infants should receive vitamin D supplementation, there should also be concern about concurrent deficiencies in infants with IDA.
doi:10.5045/br.2013.48.1.40
PMCID: PMC3624995  PMID: 23589794
Iron deficiency anemia; Vitamin D deficiency; 25(OH)D; Breastfeeding
19.  The effect of hepatectomy on the synthesis of 25-hydroxyvitamin D3. 
Journal of Clinical Investigation  1976;57(5):1213-1220.
The metabolism of [3H]vitamin D3 in hepatectomized vitamin D-deficient rats has been studied. Hepatectomy drastically disrupts vitamin D3 metabolism as revealed by prolonged high levels of [3H] vitamin D3 in the plasma compartment even 12 h after dose in contrast to sham-operated controls. Some conversion of [3H] vitamin D3 to [3H]25-hydroxyvitamin D3 was detected in hepatectomized rats, but the amount was small in spite of the high circulating levels of [3H]vitamin D3. Since the liver initially takes up much of an administered dose in normal animals and the conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 is small in hepatectomized rats in spite of high circulating [3H]-vitamin D3, it is concluded that the liver plays a major role in the metabolism of vitamin D3 to 25-hydroxy-vitamin D3.
Images
PMCID: PMC436774  PMID: 1262467
20.  Bioavailability and Efficacy of Vitamin D2 from UV-Irradiated Yeast in Growing, Vitamin D-Deficient Rats 
New food sources are needed to bridge the gap between vitamin D intake and recommended intake. We assessed the bioavailability and efficacy of vitamin D in an 8 week dose–response study of bread made with vitamin D2-rich yeast compared to vitamin D3 in growing, vitamin D-deficient rats. Plasma 25-hydroxyvitamin D (25OHD) levels increased in a curvilinear, dose-dependent manner with both forms of vitamin D, but rats fed vitamin D2-rich yeast achieved lower levels than rats fed vitamin D3. Rats fed the highest doses of vitamin D had significantly greater (p < 0.05) trabecular BMC, BMD, bone volume, and connectivity density, and greater midshaft total cross-sectional area, compared to rats on the vitamin D-deficient diets, with no significant difference due to vitamin D source. Vitamin D2-rich yeast baked into bread is bioavailable and improves bone quality in vitamin D-deficient animals.
doi:10.1021/jf104679c
PMCID: PMC3235799  PMID: 21332187
Vitamin D; fortification; bioavailability; bone; rats
21.  Vitamin D deficiency and prognostics among patients with pancreatic adenocarcinoma 
Background
The prevalence of vitamin D deficiency among patients with cancer has been previously reported. Because vitamin D is fat soluble, patients with pancreatic adenocarcinoma may have an especially high risk of vitamin D deficiency in association with ongoing and varying degrees of malabsorption. However, little is known about the correlation between vitamin D status and prognosis in these patients.
Methods
We conducted a retrospective review of vitamin D status in patients with pancreatic adenocarcinoma who were treated at Siteman Cancer Center. Patients’ demographic information, clinical staging at the time of vitamin D assessment, vitamin D levels, and survival data were collected. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25[OH]D) level of less than 20 ng/mL, and vitamin D insufficiency was defined as a 25(OH)D level of between 20 ng/mL and 30 ng/mL.
Results
Between December 2007 and June 2011, 178 patients with pancreatic adenocarcinoma had their vitamin D levels checked at the time of initial visit at this center. Of these 178 patients, 87 (49%) had vitamin D deficiency, and 44 (25%) had vitamin D insufficiency. The median 25(OH)D level was significantly lower among nonwhite patients and among patients with stage I and II disease. A 25(OH)D level of less than 20 ng/mL was found to be associated with poor prognosis (p = 0.0019) in patients with stage III and IV disease.
Conclusions
Vitamin D insufficiency and deficiency were prevalent among patients with pancreatic adenocarcinoma. The vitamin D level appears to be prognostic for patients with advanced pancreatic adenocarcinoma, and its effects should be further examined in a prospective study.
doi:10.1186/1479-5876-11-206
PMCID: PMC3844423  PMID: 24011168
Vitamin D; Vitamin D receptor; Pancreatic cancer; Prognostic factors
22.  Sunlight exposure or vitamin D supplementation for vitamin D-deficient non-western immigrants: a randomized clinical trial 
Osteoporosis International  2010;22(3):873-882.
Summary
Vitamin D deficiency is very common in non-western immigrants. In this randomized clinical trial, vitamin D 800 IU/day or 100,000 IU/3 months were compared with advised sunlight exposure. Vitamin D supplementation was more effective than advised sunlight exposure in improving vitamin D status and lowering parathyroid hormone levels.
Introduction
Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 25 nmol/l) is common among non-western immigrants. It can be treated with vitamin D supplementation or sunlight exposure.
Methods
To determine whether the effect of vitamin D3 supplementation (daily 800 IU or 100,000 IU/3 months) or sunlight exposure advice is similar with regard to serum 25(OH)D and parathyroid hormone (PTH) concentrations. Randomized clinical trial in 11 general practices in The Netherlands. Non-western immigrants, aged 18–65 years (n = 232) and serum 25(OH)D < 25 nmol/l were randomly assigned to supplementation (daily 800 IU or 100,000 IU/3 months) or advice for sunlight exposure for 6 months (March–September). Blood samples were collected at baseline, during treatment (3 months, 6 months), and at follow-up (12 months). Statistical analysis was performed with multilevel regression modelling.
Results
The intention-to-treat analysis included 211 persons. Baseline serum 25(OH)D was 22.5 ± 11.1 nmol/l. After 6 months, mean serum 25(OH)D increased to 53 nmol/l with 800 IU/day, to 50.5 nmol/l with 100,000 IU/3 months, and to 29.1 nmol/l with advised sunlight exposure (supplementation vs sunshine p < 0.001). Serum PTH decreased significantly in all groups after 3 months, more in the supplementation groups than in the advised sunlight group (p < 0.05). There was no significant effect on physical performance and functional limitations.
Conclusion
Vitamin D supplementation is more effective than advised sunlight exposure for treating vitamin D deficiency in non-western immigrants.
doi:10.1007/s00198-010-1343-x
PMCID: PMC3034877  PMID: 20683712
Non-western immigrants; RCT vitamin D; Secondary hyperparathyroidism; Sunlight exposure; Vitamin D deficiency; Vitamin D supplementation
23.  Effect of age on the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 by kidney of rat. 
Journal of Clinical Investigation  1980;66(5):1118-1123.
The decreased absorption of calcium by the small intestine of the adult may reflect changes in vitamin D metabolism with age. The purpose of this study was to compare the capacity of young (1.5 mo of age) and adult (12 mo of age) vitamin D-deficient rats to convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the physiologically active form of vitamin D. Young rats responded to an oral dose of 25-hydroxyvitamin D3 with significantly increased intestinal absorption of calcium and a three-fold increase in the intestinal content of vitamin D-stimulated calcium-binding protein. Adult rats showed no significant increase in these parameters. The conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 was measured in the whole animal by administering a dose of tritiated 25-hydroxyvitamin D3 and determining the appearance of tritiated metabolites in plasma and small intestine. In the adult rat, only 2.1 +/- 0.6% of the plasma radioactivity was in the form of 1,25-dihydroxyvitamin D3 after 24 h compared with 20.8 +/- 3.0% in the young. The conversion of tritiated 25-hydroxyvitamin D3 to its products was also measured directly in isolated slices of renal cortex. 1,25-Dihydroxyvitamin D3 production by adult renal slices was found to be less than one-tenth that of slices from the young. These results indicate that there is a marked decrease in the capacity of the vitamin D-deficient adult rat to convert 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3. This is probably due to the decreased capacity of the adult kidney to 1-hydroxylate 25-hydroxyvitamin D3. These studies also demonstrate the usefulness of renal slices in measuring changes in the renal conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 in the mammal.
PMCID: PMC371550  PMID: 6893596
24.  Osteomalacia and vitamin D deficiency in a psychiatric rehabilitation unit: case report and survey 
BMC Research Notes  2009;2:82.
Background
Vitamin D deficiency is common and predisposes to many serious diseases, yet often goes unrecognized.
Findings
We describe a case of severe vitamin D deficiency with osteomalacia in a patient resident in a psychiatric hospital for more than 35 years, and discuss causes and complications. We assayed the serum 25-hydroxyvitamin D levels of all patients under our care on one old-age psychiatry rehabilitation unit. Ten of twelve (83%) of patients had vitamin D deficiency, and 92% had suboptimal vitamin D levels. Vitamin D status was strongly predicted by dietary supplementation. Of those not on vitamin D supplements, 100% had vitamin D deficiency, with vitamin D levels significantly below those of historical controls. Age, sex, and duration of admission did not predict vitamin D status in this group.
Conclusion
We advocate vitamin D screening in all patients admitted to psychogeriatric units, and discuss treatment options given the current problems affecting high-dose vitamin D supply to the United Kingdom.
doi:10.1186/1756-0500-2-82
PMCID: PMC2683864  PMID: 19426538
25.  Severe Anaemia during Late Pregnancy 
Vitamin B12 deficiency is uncommon in pregnancy, it occurs in 10–28% of uncomplicated pregnancies, and is associated with a few complications. We present a case report of a 21-year-old patient with severe anaemia during late pregnancy caused by vitamin B12 deficiency. At 38 weeks gestation and with a BMI of 48.9, a history of rupture of membranes was given but not confirmed. On examination, she appeared pale and therefore full blood counts were done. Interestingly her haemoglobin (Hb) levels were 3.7 g/dL. Folate and vitamin B12 levels were also found to be low, and the diagnosis of anaemia caused by vitamin B12 deficiency was made. After treatment with vitamin B12 injections, folic acid and blood transfusions, the patient's haemoglobin levels improved from 3.7 g/dL to 10.7 g/dL. The conclusion is that effective history taking, diagnosis, and management can prevent many complications that are usually associated with vitamin B12 deficiency anaemia.
doi:10.1155/2012/485452
PMCID: PMC3439950  PMID: 22988533

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