The effect of a combined oral calcium and vitamin D supplement for treating mild to moderate vitamin D deficiency in postmenopausal women

Terry Golombick, Terry DiamondDepartment of Endocrinology, St George Hospital, Kogarah, Sydney, NSW, AustraliaObjective: To evaluate the efficacy of a combined calcium and vitamin D (Ca-D3) supplement for vitamin D deficiency in a small group of postmenopausal women.Methods: A prospective open label 3 month-study.Participants: 23 postmenopausal women (mean age 61.2 yrs) with vitamin D deficiency were given a combined oral Ca-D3 supplement called “Osteoblast”. The supplement comprises 500 mg elemental calcium and 500 IU of cholecalciferol. The dosing regimen comprised a loading dose of 1000 IU of cholecalciferol per day for one month (two tablets) and thereafter a maintenance dose of 500 IU of cholecalciferol per day for 2 months (one tablet).Outcome measure: Serum was collected for calcium, 25 hydroxyvitamin D3 (25OHD3), and PTH measurements, as well as early morning 2-hour urine calcium/creatinine excretion index (Uca/creat). Specimens were collected at baseline and after 3 months of therapy. Data are reported as mean ± 1 standard error and 95% confi dence intervals.Results: Data was available for the 21 subjects who completed the study. Two subjects (9%) withdrew because of gastrointestinal intolerance. There were 3 subjects with moderate (12.5–24 nmol/L) and 18 with mild (25–49 nmol/L) vitamin D deficiency. Ten subjects (48%) had secondary hyperparathyroidism. Following the oral Ca-D3 combination, serum 25OHD3 levels normalised in all subjects with 18 (86%) subjects achieving values of greater than 70 nmol/L. Serum 25OHD3 levels increased from 36 (31–41) to 91 (79–102) nmol/L (p = 0.0001), increasing by an average of 152% over the 3-month period. There was a corresponding 38% decrease in serum PTH concentrations at 3 months (5.1 + 0.6 pmol/L), compared with baseline (8.0 + 1 pmol/L) (p = 0.001). No subject developed hypercalcemia, but an elevated Uca/creat excretion index occurred in one subjects.Conclusions: A combined oral Ca-D3 product (Osteoblast) is effective for treating vitamin D deficiency and is adequately tolerated

The potential role of curcumin (diferuloylmethane) in plasma cell dyscrasias/paraproteinemia

Plasma cell dyscrasias, most commonly associated with paraproteinemia, are a diverse group of diseases. Monoclonal gammopathy of undefined significance (MGUS) can precede multiple myeloma, a progressive neoplastic disease. MGUS occurs in association with a variety of other diseases and currently no treatment is recommended but rather “watchful waiting”. Given that the size of the M-protein is a risk factor for disease progression, early intervention with the aim of reducing the paraprotein load would provide an innovative therapeutic tool. Preliminary results from our pilot study show a drop of between 5% and 30% serum paraprotein in patients taking curcumin compared with patients on placebo. Curcumin is a diferuloylmethane present in extracts of the rhizome of the Curcuma longa plant. As a natural product, this has exciting potential in the treatment of plasma cell dyscrasias

Addition of rice bran arabinoxylan to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies (monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or stage 0/1 chronic lymphocytic leukemia): a preliminary clinical study

Hypothesis. Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design. Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods. Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results. Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion. Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1-Risk Myelodysplastic Syndrome-A Small, Investigative Study

Background: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. Aim: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. Method: Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. Results: 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. Discussion: In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis

Rice bran arabinoxylan compound and quality of life of cancer patients (RBAC-QoL): Study protocol for a randomized pilot feasibility trial

© 2020 Introduction: Rice bran arabinoxylan compound (RBAC) is a nutraceutical for enhancing a depleted immune system during and after cancer treatment. This pilot feasibility trial aims to evaluate the effects of RBAC on cancer patients\u27 quality of life during active treatment, compared to placebo, using a validated questionnaire. Other outcome measures include changes in inflammatory and nutritional status, cytokine profile, and gut microbiota. Methods/Design: The study will recruit 50 participants from a regional cancer center in Australia. Patients aged 18–70, diagnosed with solid organ cancers stage II and above, and currently undergoing active systemic therapies, are eligible. Random allocation of participants into two groups is stratified based on metastatic status and treatment type. The dosage is either 3 g/day of RBAC or placebo in identical packaging. The participants, study coordinator, and treating oncologists are blinded to the interventions. Data collections are at baseline and at four follow-up sessions, which are six weeks apart (24 weeks). Statistical analysis will involve a protected p-value with multiple dependent values and analyzed by ANOVA with repeated measures on the occasion of testing and with both a full Bonferroni or Sidak corrections applied to protect against Type I errors. Any observed significance warrants further analysis with pairwise comparisons. Analysis of covariance will also be performed to assess any influence of the demographic data, cancer diagnosis, as well as changes in physical activity, dietary habits, and complementary medicine usage. Comparisons of gut microbiota will be based on the analysis of the fecal microbiome using 16S ribosomal ribonucleic acid amplicon sequencing. The proposed research timeline is from October 2018 to May 2022. Trial registration: ANZCTR. Reg No: ACTRN12619000562178p

Monoclonal gammopathy of undetermined significance and bone health outcomes: a systematic review and exploratory meta-analysis

Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in the elderly. A number of studies have investigated the relationship between MGUS and bone health outcomes including bone mineral density (BMD), osteoporosis and fractures, but no meta-analysis exists. We conducted a systematic review and exploratory meta-analysis comparing bone health outcomes in patients with MGUS. Two independent authors searched PubMed and Scopus from inception until 19 October 2016. A meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD was conducted. Standardised mean differences (SMD) ± 95% confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures. Of 174 initial hits, 10 studies of moderate methodological quality were eligible, including 8711 individuals with MGUS vs. 52,865 controls. Compared to controls, subjects with MGUS showed significantly lower values for radial cortical volumetric BMD (1 study; SMD = -5.45, 95% CI: -7.24 to -3.66), but not at the lumbar spine, femoral neck or hip. The incidence of fractures was higher in people with MGUS (n = 7466) vs. controls (n = 52,304) (RR = 1.36, 95% CI 1.28-1.44, I 2 = 0%) over a median of 12.5-year follow-up. The incidence of vertebral fractures was particularly elevated (RR = 2.50, 95% CI 1.53-4.06) although limited to two studies. In conclusion, although with limitations, our preliminary meta-analysis suggests that patients with MGUS are at higher risk of fractures despite evidence for differences in BMD being equivocal. Future longitudinal research is required to confirm our findings and determine if fracture prevention interventions are warranted in people with MGUS

Use of Curcumin in Multiple Myeloma patients intolerant of steroid therapy

Curcumin, when used in a combination regimen in multiple myeloma patients, has comparable progression-free survival without the adverse effects of steroid-based combination therapies that is curcumin may be a viable alternative to corticosteroids in combination with an immunomodulatory drug or proteasome inhibitor

The effect of curcumin (as Meriva) on absolute lymphocyte count (ALC), NK cells and T cell populations in patients with stage 0/1 chronic lymphocytic leukemia

Purpose: To determine the effect of curcumin (as Meriva) on absolute lymphocyte count (ALC), T cell populations and NK cells in patients with Rai stage 0/1 chronic lymphocytic leukemia (CLL) over a period of six months. Experimental Design: Twenty-one patients with significant lymphocytosis (\u3e20 x 109 lymphocytes/L) and stage 0/1 CLL were recruited into the study and received oral curcumin 2 grams/day. Blood samples were collected at baseline and at 2 monthly intervals for six months for full blood count, leukocyte surface antigens, liver function, serum biochemistry, immunoglobulins, CRP and ESR. A positive biologic response was defined as a reduction in the ALC of more than 20% from pre-treatment levels. Results: Four patients (20%) demonstrated more than 20% decrease in ALC, three of whom had lower ALC at the end of the study as compared to baseline. The decrease in ALC was accompanied by an increase in CD4, CD8 and NK cells. No demonstrable response was seen in seventeen patients (80%) who exhibited stable, fluctuating or increasing ALC during the study. Conclusion: A subgroup of stage 0/1 CLL patients may be responsive to curcumin therapy. The beneficial response appears to be immunomodulated