Effect of Vitamin D Supplementation in Type 2 Diabetes Patients with Tuberculosis: A Systematic Review

Background: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as re-emerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity. Objective: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients. Method: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review. Result: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters including HbA1c, FBS, and PLBS, and laboratory parameters such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant. Conclusion: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population.

Low serum 1,25(OH)2D3 in end stage renal disease – is reduced 1α-hydroxylase the only problem?

Low serum 1,25-dihydroxyvitamin D (1,25(OH)2D) in end stage renal disease (ESRD) is considered a consequence of elevated fibroblast growth factor 23 (FGF23) and concomitant reduced activity of renal 1α-hydroxylase (CYP27B1). Current ESRD treatment strategies to increase serum calcium and suppress secondary hyperparathyroidism involve supplementation with vitamin D analogues that circumvent 1α-hydroxylase. This overlooks the potential importance of 25-hydroxyvitamin D (25(OH)D) deficiency as a contributor to low serum 1,25(OH)2D. We investigated the effects of vitamin D (cholecalciferol) supplementation (40,000IU for 12 weeks and maintenance dose of 20,000IU fortnightly), on multiple serum vitamin D metabolites (25(OH)D, 1,25(OH)2D3 and 24,25(OH)2D3) in 55 haemodialysis patients. Baseline and 12 month data were compared using related-samples Wilcoxon signed rank test. All patients remained on active vitamin D analogues as part of routine ESRD care. 1,25(OH)2D3 levels were low at baseline (normal range 60-120pmol/L). Cholecalciferol supplementation normalised both serum 25(OH)D and 1,25(OH)2D3. Median serum 25(OH)D increased from 35.1nmol/L (IQR 23.0-47.5nmol/L) to 119.9nmol/L (IQR 99.5-143.3nmol/L) (P<0.001). Median serum 1,25(OH)2D3 and 24,25(OH)2D3 increased from 48.3pmol/L (IQR 35.9-57.9pmol/L) and 3.8nmol/L (IQR 2.3-6.0nmol/L) to 96.2pmol/L (IQR 77.1-130.6pmol/L) and 12.3nmol/L (IQR 9-16.4pmol/L), respectively (P<0.001). A non-significant reduction in daily active vitamin D analogue dose occurred, 0.79mcg at baseline to 0.64mcg at 12 months (P=0.73). The ability to synthesise 1,25(OH)2D3 in ESRD is maintained but is substrate dependent, and serum 25(OH)D was a limiting factor at baseline. Therefore, 1,25(OH)2D3 deficiency in ESRD is partly a consequence of 25(OH)D deficiency, rather than solely due to reduced 1α-hydroxylase activity as suggested by current treatment strategies.

Bone Metabolism In Patients With Type 1 Neurofibromatosis: Key Role of Sun Exposure and Physical Activity

Bone metabolism has been rarely investigated in children affected by Neurofibromatosis (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and BMD data obtained during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry (DXA) than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced BMD (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z.score (p = 0.000). We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. We also demonstrated that treatment with vitamin D can be effective in improving BMD in NF1 patients, including children. In conclusion, the findings of the current study are expected to have important implications for the follow-up and prevention of osteopenia/osteoporosis in this common genetic disease.

Health-Related Quality of Life In T1DM Patients After High-Dose Cholecalciferol Supplementation.

Background: Type 1 Diabetes Mellitus (T1DM) impacts health-related quality of life (HRQoL). Cross-sectional studies suggest that low levels of vitamin D (VD) may impair HRQoL, however, the effect of VD supplementation on quality of life in patients with T1DM has not yet been clarified. The objective of the study was to evaluate the effects of high-dose VD supplementation on HRQoL in patients with T1DM. Methods: We performed a prospective interventional study with 64 patients supplemented with high doses of cholecalciferol (4,000 IU/day for patients with 25-OH-vitamin D [25(OH)D] between 30 and 60 ng/mL, and 10,000 IU/day for those with 25(OH)D below 30 ng/mL) for 12 weeks. HRQoL was assessed with EuroQol instruments (EQ-5D and EQ-VAS). Results: There was an improvement in global EQ-5D index at the end of vitamin D supplementation. Analysing only the EQ-5D domains, we observed particularly an improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p <0.01). Evaluating possible outcome influencing variables, we detected a reduction in albuminuria at the end of the trial, without changes in BMI, lipids, blood pressure, glycemic control, insulin doses and in peripheral diabetic neuropathy. We also found a correlation between final albuminuria and the dimensions: mobility (r = 0.6; p <0.01), personal care (r = 0.7; p <0.01), pain and discomfort (r = 0.6; p <0.01) and habitual activities (r = 0.6; p <0.01), suggesting an association between albuminuria reduction and the impact of VD supplementation on HRQoL. Conclusion: Our data showed that high doses of cholecalciferol supplementation can improve HRQoL in patients with T1DM, and the reduction of albuminuria seems to be an important factor in this context.Trial registration: ISRCTN, ISRCTN32601947. Registered 3 June 2017 - Retrospectively registered, http://www.isrctn.com/ISRCTN32601947

VITADIAL “Does correction of 25 OH-VITAmin D with cholecalciferol supplementation increase muscle strength in hemoDIALysis patients?”: study protocol for a randomized controlled trial

Background Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength. Methods/design VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient’s autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective. Discussion In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient’s muscle strength. Trial registration ClinicalTrials.govNCT04262934. Registered on 10 February 2020 - Retrospectively registered.