Purpose: To determine the effect of curcumin on plasma cells and osteoclasts in patients with MGUS. Experimental Design: Twenty-six patients with MGUS were recruited into the study and administered 4 grams/day oral curcumin. Blood and urine samples were collected at specified visits after initiating therapy. Full blood count, B2 microglobulin, serum paraprotein, and immunoglobulin electrophoresis (IEPG and EPG) were determined for all patients at each visit. Serum calcium, 25 hydroxyvitamin D3, and bone-specific alkaline phosphatase were determined at baseline only. Urine, as a morning second-void sample, was collected at each visit for urinary N-telopeptide of type I collagen. Results: Our results show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of >20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a >25% decrease in urinary N-telopeptide of type I collagen. Conclusion: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation. (Clin Cancer Res 2009;15(18):5917-22) Plasma cell dyscrasias, most commonly associated with paraproteinaemia, are a diverse group of disorders that includes multiple myeloma, Waldenstrom's macroglobulinaemia, heavy chain disease, monoclonal gammopathy of undefined significance (MGUS), and immunocytic amyloidosis. The incidence of plasma cell dyscrasias is age related, occurring in 1% of persons over age 25 years and 4% of those over age 70 years.MGUS is the most common of the monoclonal gammopathies. At Mayo Clinic, almost 60% of patients with a monoclonal gammopathy have MGUS (1). MGUS can precede multiple myeloma and is typified by a serum M-protein value of <30 g/L, fewer than 10% plasma cells in the bone marrow, no or a small amount of M protein in the urine, and absence of lytic bone lesions, anemia, hypercalcemia, or renal insufficiency related to the plasma-cell proliferative process (1). Myeloma is a progressive neoplastic disease and is characterized by high bone turnover, significant bone loss, and pathologic fractures resulting in significant morbidity and a high mortality. It is also associated with hypercalcemia, anemia, renal damage, and increased susceptibility to bacterial infections.Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover. Although MGUS is largely considered a benign condition, a number of studies show that patients with MGUS are at increased risk of developing fractures even before progression to myeloma (2).Elevated bone turnover is an independent predictor of fracture risk, and a number of studies have shown elevated bone resorption and/or reduced bone formation among patients with MGUS and myeloma (3, 4). A study by Diamond et al. (5) found that in a...

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) represent useful models for studying multiple myeloma precursor disease, and for developing early intervention strategies. Administering a 4g dose of curcumin, we performed a randomised, double-blind placebo-controlled cross-over study, followed by an open-label extension study using an 8g dose to assess the effect of curcumin on FLC response and bone turnover in patients with MGUS and SMM. 36 patients (19 MGUS and 17 SMM) were randomised into two groups: one received 4g curcumin and the other 4g placebo, crossing over at 3 months. At completion of the 4g arm, all patients were given the option of entering an open-label, 8g dose extension study. Blood and urine samples were collected at specified intervals for specific marker analyses. Group values are expressed as mean ± 1 SD. Data from different time intervals within groups were compared using Student's paired t-test. 25 patients completed the 4g cross-over study and 18 the 8g extension study. Curcumin therapy decreased the free light-chain ratio (rFLC), reduced the difference between clonal and nonclonal light-chain (dFLC) and involved free light-chain (iFLC). uDPYD, a marker of bone resorption, decreased in the curcumin arm and increased on the placebo arm. Serum creatinine levels tended to diminish on curcumin therapy. These findings suggest that curcumin might have the potential to slow the disease process in patients with MGUS and SMM. Am. J. Hematol. 87:455-460, 2012. V

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Introduction: Conventional cancer treatment, including surgery, chemotherapy, and radiotherapy, may not be sufficient to eradicate all malignant cells and prevent recurrence. Intensive treatment often leads to a depressed immune system, drug resistance, and toxicity, hampering the treatment outcomes. BioBran/MGN-3 Arabinoxylan is a standardized arabinoxylan concentrate which has been proposed as a plant-based immunomodulator that can restore the tumor-induced disturbance of the natural immune system, including natural killer cell activity to fight cancer, complementing conventional therapies. Objectives: To comprehensively review the available evidence on the effects and efficacies of MGN-3 as a complementary therapy for conventional cancer treatment. Methods: Systematic search of journal databases and gray literature for primary studies reporting the effects of MGN-3 on cancer and cancer treatment. Results: Thirty full-text articles and 2 conference abstracts were included in this review. MGN-3 has been shown to possess immunomodulating anticancer effects and can work synergistically with chemotherapeutic agents, in vitro. In murine models, MGN-3 has been shown to act against carcinogenic agents, and inhibit tumor growth, either by itself or in combination with other anticancer compounds. Fourteen successful MGN-3 treated clinical cases were found. Eleven clinical studies, including 5 nonrandomized, pre-post intervention studies and 6 randomized controlled trials (RCTs) were located. Reported effects include enhanced immunoprofile, reduced side effects, improved treatment outcomes; one RCT established significantly increased survival rates. There are no reports on adverse events on MGN-3. Most of the clinical trials are small studies with short duration. Conclusion: There is sufficient evidence suggesting MGN-3 to be an effective immunomodulator that can complement conventional cancer treatment. However, more well-designed RCTs on MGN-3 are needed to strengthen the evidence base.

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 (>20 × 10 9 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.

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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.

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