Vitamin D: drug of the future. A new therapeutic approach

Besides increasing calcium absorption in the bowel and promoting the normal formation and mineralization of bone, vitamin D exerts relevant pleiotropic effects in different tissues. Serum levels of vitamin D show correlation with the risk of infections, cardiovascular diseases, cancer and autoimmune disorders. The possible therapeutic role of vitamin D in different kind of diseases: inflammatory, immunologic, infectious and neoplastic ones, explains the growing interest in this vitamin due to its pleiotropic effects, and makes it a candidate to become a potential drug in the next future.     

Effects of dairy food supplements on bone mineral density in teenage girls

Summary Background Bone mineral density (BMD) is largely genetically determined and this influence is most powerful in the period of rapid skeletal development in childhood and late adolescence but environmental factors such as exercise and dietary calcium intake may influence up to 20%. Aims of the study The aims of the study were to examine healthy late adolescent females for the effects and benefits of a high calcium intake from dairy product foods on bone mineral density, body composition, lipids and biochemistry. The secondary aim is determine whether a high intake of dairy product foods in the diet is acceptable for this age group long term. Methods Ninety-one teenage girls who participated in a two-year randomised controlled study on the effect of dairy food supplementation on dietary patterns, body composition and bone density in post-pubertal teenage girls were approached one year after the cessation of the study to determine the effects of the cessation of dairy supplements on bone mineral density, dietary habits, biochemical markers, body composition and blood lipids. Bone mineral density and bone mineral content were assessed at the hip, spine and total body. Anthropometric data were collected, and exercise, Tanner, dietary assessment, preference and compliance questionnaires were administered. Lipid profiles, hydroxyproline excretion and urinary calcium and sodium excretion measurements were performed. Results There were no significant differences between the 2 groups for height, weight, lean and fat mass. The supplemented group had significantly higher calcium, phosphorus and protein intake during the supplementation period (p<0.001). No differences were seen between the groups 12 months after supplementation finished. There were no significant differences in exercise level, preference or acceptability of dairy products or in the lipids and bone markers between baseline the end of supplementation and 1 year follow-up. There was a significant increase in trochanter (4.6%), lumbar spine (1.5%) and femoral neck (4.8%) BMD (p<0.05) in the high calcium group at the end of supplementation. There was an increase in bone mineral content at the trochanter (p<0.05) and lumbar spine; however the latter was not statistically significant, in the high calcium group at the end of supplementation. There was no difference in vertebral height or width at any stage of the study, indicating no influence on bone size. Conclusions In this 3 year study (2 years of supplementation, 1 year follow-up), teenage girls, aged 15–18 years, were able to significantly increase their BMD at the trochanter, femoral neck and lumbar spine when supplemented with dairy product foods to a mean calcium intake of 1160 mg/d. There was also an effect seen on the BMC particularly at the trochanter and to a lesser extent at the lumbar spine. The dietary calcium intake achieved did not adversely affect body weight, fat and lean mass or blood lipid profiles. Twelve months after the supplementation finished the girls had returned to their baseline diet, indicating self-selection of a high dairy product diet may be hard to achieve. Received: 5 June 2000, Accepted: 5 September 2000     

Plasma glutathione peroxidase after selenium supplementation in patients with reduced selenium state

The plasma glutathione peroxidase (GSHPx) activity was measured in normal adults and children and in patients with reduced selenium state because of dietary treatment of metabolic diseases (phenylketonuria or maple-syrup-urine disease) before and after selenium supplementation. Besides GSHPx (measured with t-butyl hydroperoxide, cumene hydroperoxide and hydrogen peroxide as acceptor substrates) the activity of glutathione S-transferase was estimated in plasma. Plasma GSHPx activity in healthy children was significantly lower than in healthy adults. In 11 dietetically treated patients with phenylketonuria or maple-syrup-urine disease the plasma GSHPx was reduced to about 17% of the values of healthy children of the same age. No glutathione S-transferase activity could be found in plasma of children in normal or reduced Se state.During administration of yeast rich in Se (200g Se/d) for 90 days 2 healthy adults showed no significant change of plasma GSHPx activity. During Se supplementation (75–100g Se/d) for 120–163 days 5 dietetically treated patients with PKU or MSUD exhibited a significant increase of plasma GSHPx activity within 2 days. The values reached a plateau after 1 to 3 weeks of supplementation and remained at this level within the following 4 to 5 months. Therefore, the activity of plasma glutathione peroxidase can be used as an indicator of short-term changes of selenium intake in selenium deficient individuals.Abbreviations (PKU) Phenylketonuria - (MSUD) maple-syrup-urine disease - (GSHPx) glutathione peroxidase - (t-BOOH) t-butyl hydroperoxide - (COOH) cumene hydroperoxide - (H₂O₂) hydrogen peroxide - (GSH) reduced glutathione With support of the Deutsche Forschungsgemeinschaft     

Hyperhomocysteinemia and the response to vitamin supplementation

Summary The long-term vitamin requirements of men (n=22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 mol/1) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P<0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 mol/l or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomo-cysteinemia.Abbreviations HPLC high-performance liquid chromatography - Lp(a) lipoprotein(a) - PLP pyridoxal 5-phosphate     

The predictive characteristics of D-dimer testing in outpatients with suspected venous thromboembolism: a Bayesian approach

BACKGROUND: Despite the widespread use of quantitative methods to measure D-dimer, clinical decisions commonly are based only on binary test information (positive/negative). This study aimed to determine the significance of quantitative D-dimer results in the evaluation of venous thromboembolism (VTE) by means of a differentiated Bayesian approach. METHODS: Prospective study in 118 outpatients referred for workup of suspected pulmonary embolism (n = 75) or deep vein thrombosis (n = 43). The sensitivity and specificity of D-dimer results obtained by DD VIDAS (Biomerieux, France), STA Liatest (Diagnostica Stago, France), and D-dimer plus (Dade, US) were assessed for five different cut-offs. Further, predictive values and multilevel likelihood ratios were calculated in order to assess the operative test characteristics in excluding or confirming VTE. RESULTS: At a cut-off of 500 ng/ml and pretest probabilities < 47%, the VIDAS provides a negative predictive value (NPV) > 95%, whereas a positive predictive value (PPV) > 95% is obtained in patients with a D-dimer > 10,000 ng/ml and pretest probabilities > 50%. At a cut-off of 500 ng/ml and pretest probabilities < 33%, the Liatest exhibits a NPV > 95%, whereas a PPV > 95% is obtained in patients with a D-dimer >10,000 ng/ml and pretest probabilities > 37%. Finally, with the D-dimer plus, a NPV > 95% is seen at a cut-off of 150 ng/ml and pretest probabilities < 30%, whereas a PPV > 95% is obtained at a cut-off > 1000 ng/ml and pretest probabilities > 67%. CONCLUSIONS: D-dimer measurements in outpatients cannot only allow for exclusion but, in some situations, also for confirmation of venous thromboembolism. It is therefore advisable to conduct a quantitative interpretation of D-dimer results.     

Efficacy of Oral Zinc Sulfate Supplementation on Clearance of Cervical Human Papillomavirus (HPV); A Randomized Controlled Clinical Trial

Aim: Human Papillomavirus is one of the most crucial infectious disease in gynecology disease. To assess the efficacy of supplemental zinc treatment in clearance of HPV infection. Methods: Eighty zinc-sufficient women between 21-55 years, with positive HPV DNA testing, and abnormal cervical cytology in Pap test (ASCUS or LISL) were randomly divided to case (n=40) and control group (n=40). Case group received oral tablets of zinc sulfate twice a day for 3 months while control group received no placebo. During follow-up patients underwent repeat HPV DNA test and PAP test and were evaluated for clearance/persistence of HPV infection and regression/progression in the lesion grading. Results: As far as demographics, serum zinc levels and the relevant risk factors for persistence of HPV were concerned, there was no significant difference between two groups, except for the frequency distribution of HR-HPV which was significantly higher in case  group. Zinc treatment for 3 months reduced the risk of persistence of HPV infection and progression from baseline cytology (OR = 0.130) (CI 95% 0.04-0.381; p <0.001) and 0.301 (95% CI 0.777-0.116; p = 0.012), respectively. Age, initial cytology, HPV type, and contraceptive method were not related to persistence of HPV. Serum zinc levels increased in the casr group as a result of oral zinc consumption for 3-month period, though without any statistical significance (p = 0.407). Conclusion: The results of the following study suggested that oral intake of zinc sulfate supplement for 3 months increases the rates of HPV clearance and resolution of pre-existing cervical lesion.     

Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized,double blind,placebo-controlled trial

Objectives: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD.

Methods: Sixty-two children aged 5–12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed.

Results: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P?P?=?0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales.

Discussion: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism.

The trial was registered in www.irct.ir is (IRCT201404222394N10).