The Potential Role of Curcumin in Patients with Monoclonal Gammopathy of Undefined Significance—Its Effect on Paraproteinemia and the Urinary N-Telopeptide of Type I Collagen Bone Turnover Marker

Abstract

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...

Long term use of curcumin in two smoldering multiple myeloma patients

“…Both these patients showed a continued improvement in several markers of their disease activity and in particular, a decrease in % plasma cells in the bone marrow. These data are in accordance with our previous findings [5,6] . Although myeloma is a "patchy" disease, the bone histopathology failed to demonstrate progression of the disease, but suggested an improvement in the plasma cell infiltrate.…”

“…The most active component in turmeric is curcumin [2] . Based on its demonstrated anti-myeloma cell activity, both in vitro and in vivo [3,4] , we have carried out both a 6 month pilot study [5] and a 6 month randomised, double-blind placebo-controlled cross-over 4g study and a 3 month open-label 8g extension study [6] and shown that oral curcumin can, in a select group of MGUS and SMM patients, decrease free light chains (rFLC, dFLC and iFLC), paraprotein and bone resorption. Here, we present a report of two patients with SMM who were recruited into our second study [6] and who elected to continue on the same regimen of oral curcumin daily after the study.…”

Curcumine (Turmeric – Curcuma longa) as a Supportive Phytotherapeutic Treatment in Oncology

“…U 1/ 2 pa cientů, u kterých byla sérová hladina paraproteinu na začátku terapie > 20 g/ l, došlo k jeho poklesu o 12-30 %. Navíc 27 % pa cientů mělo v moči o 25 % nižší koncentraci osteoresorpčního markeru N-terminálního telopeptidu kolagenu typu I [46]. Zdá se tedy, že kurkumin může alespoň částečně blokovat osteoresorpci a snižovat tak pravděpodobnost fraktur.…”

Curcumin for the prevention of progression in monoclonal gammopathy of undetermined significance: A word of caution

“…More recently, Golombick and Diamond (2) and Golombick et al (3) reported the results of pilot studies which indicated that curcumin, in some patients with monoclonal gammopathy of undetermined significance (MGUS), decreases the paraprotein load and the urinary n-telopeptide of type 1 collagen bone turnover marker. MGUS indicates the presence of a monoclonal (M-) protein in individuals without evidence of multiple myeloma, Waldenström's macroglobulinemia, primary amyloidosis, or related disorders (4).…”

“…in a commentary on the above-mentioned study by Golombick et al (3), rajkumar emphasized the crucial importance of developing new methods to prevent the malignant progression of MGUS (11). As mentioned, MGUS often does not present symptoms, while progression leads to incurable disease.…”