Does vitamin D affect disease severity in patients with ankylosing spondylitis?

Background Vitamin D has been found to have a role in the function of the immune system. There have been a lot of studies investigating a relation between vitamin D and disease activity in ankylosing spondylitis (AS). However, there have not been any studies arranging AS in groups according to vitamin D levels and determining any differences among these patients in terms of disease activity, functional status, quality of life, and other clinical parameters. The aim of this study is to compare 25-hydroxy-vitamin D3 (25(OH)D3) levels in AS patients with those in normal healthy subjects and to determine the relationship between 25(OH)D3 levels and AS disease activity, functional status, and quality of life.

 

Methods  Ninety-nine consecutive patients and 42 healthy volunteers were included in this study. After a comparison between the patient group and the control group, the patient group was divided into normal, insufficient and deficient subgroups according to the plasma 25(OH)D3 levels for another comparison.

 

Results  The differences in the 25(OH)D3 level between the patient and the control groups were statistically insignificant. The number of AS patients whose 25(OH)D3 levels were classified as normal, insufficient, and deficient were 34, 29, and 36, respectively. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Bath AS Disease Activity Index (BASDAI) scores were higher in the low (including insufficient and deficient) 25(OH)D3 level subgroups (P <0.05). The Bath AS Functional Index (BASFI) and AS Quality of Life (ASQoL) scores were significantly different between the normal and the deficient subgroups (P <0.05).  Pain, BASDAI, ESR, and CRP were inversely correlated to the 25(OH)D3 levels (P <0.05).

 

Conclusions  The plasma 25(OH)D3 levels may decrease in AS patients and this may negatively affect disease activity, functional status and quality of life.

     

Does this elderly patient have iron deficiency anaemia,and what is the underlying cause?

Important implications for the recognition of iron deficiency anaemia include diagnosis and correction of underlying causes, most of which are identifiable, in the older patient, by means of conventional upper gastrointestinal endoscopy, and by colonoscopy. The aetiological search may, however, have to be widened to include enteroscopic examination of the jejunum and ileum and, in some instances, investigation of potential non-gastrointestinal foci of chronic blood loss. A substantial minority may defy even the most thorough search for the underlying cause.     

Assessment of low vitamin D among Saudi Arabians: Did we overshoot the runway?

Objectives:

To compare the performance of 3 commonly used 25-hydroxyvitamin D (25-OHD) assays among a sample of the Saudi population.

Methods:

This cross-sectional study was carried out between January 2011 and December 2012 at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia. After informed consent, blood samples for measurement of 25-OHD level was extracted from 200 adults. The vitamin D level of each individual were determined using chemiluminescence immunoassay (CLIA), radio-immuno assay (RIA), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Assays were also compared through commonly used cut-points for classification of vitamin D deficiency. Bias between assays was evaluated using Bland-Altman plots.

Results:

The average age of patients was 45.7±16.1 years. A significant difference between the assays was found. The mean 25-OHD levels were highest for the LC-MS/MS (21.65 ng/mL, 95% CI 19.74-23.56), intermediate for RIA (16.607 ng/mL, 95% CI 14.87-18.32), and lowest for CLIA method (13.864 ng/mL, 95% CI 12.109-15.618). Using 30 ng/mL as a cutoff value, only 6% was found to have normal levels of 25-OHD using CLIA, 9% using RIA, and 22% using LC-MS/MS.

Conclusion:

Levels of 25-OHD and the prevalence of vitamin D deficiency are dependent on the assay used. The reported high prevalence of hypovitaminosis D among the Saudi population can be partially explained by the use of assays that underestimate vitamin D levels.Vitamin D deficiency has been known for a long time to cause skeletal diseases such as rickets in children, and osteomalacia in adults.1 Apart from its importance in the management of osteoporosis, lately it was recognized that an association exists between vitamin D deficiency and many acute and chronic illnesses such as cancer, type 1 and type 2 diabetes mellitus, hypertension, cardiovascular diseases, infectious diseases, autoimmune diseases, and depression.2-7 With the improved understanding of the risks of vitamin D deficiency, more attention for the evaluation of vitamin D status has been undertaken and the clinical demand for assessment of vitamin D status has rapidly increased. In general, measurement of 25-hydroxyvitamin D (25-OHD) level in serum or plasma is accepted as a reliable indicator of vitamin D status, but assay technology needs to be able to measure both D₂ and D₃ metabolites. Thresholds of serum 25-OHD concentration to define vitamin D deficiency are highly debated, but there is a consensus agreement that vitamin D sufficiency should be defined as 25-OHD level of >75 nmol/L (>30ng/ml), insufficiency as 50-75 nmol/L (20-30 ng/ml), and deficiency as <50 nmol/L (<20 ng/ml).8 These deficiencies are widespread and it is higher in the elderly and hospitalized population.9,10 Studies from Saudi Arabia revealed a varying prevalence of vitamin D deficiency (50-100%) in all age groups.11-14 This high variability of prevalence in the same ethnic group raises the questions of reliability and accuracy of the 25-OHD assays used. With the recognized epidemic of hypovitaminosis D worldwide, it became imperative to accurately assess circulating levels of 25-OHD. However, the issue of substantial variability among different assays make clinical assessment of the vitamin D status of an individual patient problematic.15,16 Binkley et al17 reported that it is less appreciated that the assays, which are used to measure levels of 25-OHD may yield discrepant results, and they were the first to drew attention of the clinical community to the large variability in 25-OHD results both between methods and between laboratories. Several assays are being used for the measurement of vitamin D in serum or plasma including competitive binding assay, different manual and automated immunoassays, high-performance liquid chromatography (HPLC), and the lately developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, which was found to be the most accurate and is currently considered the gold standard method for the assessment of 25OHD level.18,19 King Fahd Hospital of the University, Al-Khobar, Saudi Arabia laboratory uses the chemiluminescence immunoassay (CLIA) method to assess levels of 25-OHD, and we hypothesized that such an assay is overestimating the prevalence of hypovitaminosis D. The objective of this study is to compare the performance of the CLIA assay method used at our hospital with the radio-immuno assay (RIA) and the LCMS/MS assay methods among a sample of the Saudi population.     

Northern infant syndrome: a deficiency state?

A syndrome is described that affected 16 Indian and Inuit infants roughly 3 months old, most of whom were born in settlements in the Canadian Arctic. The infants presented with a clinical picture that included hepatitis, hemolytic anemia, rickets and respiratory distress, a combination that resembled a syndrome first described in malnourished infants at the turn of the century by von Jaksch and Luzet. The clinical course was self-limited, and all the infants survived without sequelae. The cause of the syndrome was not determined; no infectious agents were discovered. However, low levels of vitamins A, C, D and E were found in a few infants in whom assays were done. The implications of these findings and their relation to the possible cause of this "northern infant syndrome" are discussed.     

Hormone replacement therapy: to use or not to use?

The main indication for hormone replacement therapy (HRT) is to control menopausal symptoms and improve quality of life. Ideally, withdrawal of HRT should be attempted after 4-5 years of therapy. HRT reduces fracture risk and remains appropriate therapy for osteoporosis, particularly in women with symptoms. HRT is not appropriate for primary or secondary cardioprotection. HRT leads to a small increase in breast cancer incidence, which increases with duration of therapy and age. HRT increases the risk of thromboembolism. Patient management and therapy should be reviewed annually with risk-benefit counselling.     

The cure of ageing: vitamin D--magic or myth?

Vitamin D was initially thought only to function in calcium homeostasis. However, it has multiple roles in human health, including neuromuscular and immune modulation. Recently, its deficiency is increasingly implicated in many diseases. This discovery has led both popular culture and research to find ways that vitamin D can either treat or prevent many diseases. Since vitamin D not only affects the expression of many genes, but also has intra-individual pharmacokinetic variation, a simplistic cause and effect between vitamin D deficiency and illnesses should not be expected. Older adults pose a challenge not only because diseases become more prevalent with ageing, but they also are often complicated with other comorbidities. This article reviews the link of vitamin D deficiency and the associated medical conditions in middle aged and older adults. It also examines the variability in testing vitamin D values and evaluates dosing recommendations based on current evidence.     

Combining vitamin A and vaccines: convenience or conflict?

The present thesis is based on 11 papers from 1995-2010. The studies have mainly taken place at the Bandim Health Project in Guinea-Bissau, West Africa, but a reanalysis of a randomised trial from Ghana is also included. My research has explored the consequences of combining high-dose vitamin A supplementation and childhood vaccines. Vitamin A deficiency is associated with increased mortality. To protect against the consequences of vitamin A deficiency the World Health Organization recommends that high-dose vitamin A supplements be given together with routine vaccines to children between 6 months and 5 years of age in more than 100 low-income countries. The recommendation is based on logistical considerations. The consequences of combining vitamin A and vaccines were not investigated in randomised trials prior to the implementation of this policy - it was assumed that the interventions were independent. My first project aimed to study the effect on the immune response to measles of providing vitamin A together with measles vaccine. We found that the two interventions were not independent. Vitamin A enhanced the antibody response to measles vaccine given at 9 months of age significantly, especially in boys. The effects were sustained over time; the children who had received vitamin A with their measles vaccine were more protected against measles at 6-8 years of age. Though vitamin A supplementation had a beneficial effect on the immune response to measles vaccine, it intrigued me that the effect of vitamin A supplementation on overall mortality was not always beneficial. While vitamin A was beneficial when given after 6 months of age, and two studies had shown a beneficial effect when given at birth, all studies testing the effect between 1-5 months of age had found no effect. These time windows are dominated by three different childhood vaccines: BCG vaccine given at birth, diphtheria-tetanus-pertussis (DTP) vaccine given between 1-5 months of age, and measles vaccine given at 9 months of age. These vaccines have been shown to have strong effects on mortality from infectious diseases in general, so-called non-specific effects. The live BCG and measles vaccine protects against more mortality than can be ascribed to the prevention of tuberculosis and measles, respectively. The inactivated DTP vaccine worryingly has been associated with increased mortality from other infectious diseases. Both positive and negative effects are strongest for girls. I proposed the hypothesis that vitamin A amplifies not only the specific vaccine effects, as we saw for measles vaccine, but also the non-specific effects of vaccines on mortality from other infectious diseases. According to my hypothesis, vitamin A would enhance the non-specific beneficial effects on mortality of BCG and measles vaccine, but also the negative effects of DTP vaccine. Hence, the hypothesis offered an explanation for the mortality-age pattern after vitamin A supplementation. Since it was formulated, I have aimed to test this hypothesis. Since it is associated with ethical problems to randomise children above 6 months of age to vitamin A supplementation, and to randomise children in general to recommended vaccines, we have had to be pragmatic when designing the trials. Hence, our studies have taken many different forms. We conducted an observational study during a vitamin A campaign in which missing vaccines were also provided, and a randomised trial testing the effect of two different doses of vitamin A during another campaign; we tested the effect of providing vitamin A with BCG at birth in two randomised trials, and we reanalysed data from one of the original randomised trials of vitamin A supplementation from the perspective of vaccination status. In all studies the main outcome was mortality. The results document that vitamin A supplements do more than protect against vitamin A deficiency. They support the hypothesis that vitamin A supplements interact with vaccines with important consequences for mortality. First, a smaller dose of vitamin A was more beneficial than a larger dose for girls. Second, the effect of vitamin A given with DTP vaccine was significantly different from the effect of vitamin A given with measles vaccine, and children, who received vitamin A with DTP vaccine, had higher mortality than children, who had received vitamin A alone, or who did not receive anything. Third, vitamin A given with BCG at birth interacted negatively with subsequent DTP vaccines in girls. Fourth, the effect of vitamin A to older children in Ghana depended on vaccination status, being beneficial in boys, but harmful in girls who received DTP vaccine during follow-up. The results also show that boys and girls respond differently to vitamin A and vaccines. It is a common assumption within public health in low-income countries that interventions can be combined without producing unexpected consequences. The work presented in this thesis confronts this assumption; the results show that vitamin A and vaccines should be seen not only as specific interventions with specific and independent effects, but as immuno-modulators, which can interact with important consequences for overall mortality. Combining interventions can be convenient and lead to synergistic health benefits, but we documented several examples, where it also leads to unexpectedly increased mortality. Thus, to optimise the child health intervention policy in low-income countries a shift in paradigm is needed. Health interventions should no longer be seen as merely specific and independent, and the policy should probably not be the same for boys and girls. Though more complex, it is necessary to evaluate all health interventions in terms of their effect on overall mortality - and their potential interactions with other health interventions and potential sex-differential effects should always be investigated. Only in this way can we assure that the children in the poorest countries get the best possible treatment and avoid using large amounts of money and resources on interventions which may, in worst case, kill them.