Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and Curcumin: A randomized, double-blind placebo controlled cross-over 4 g study and an open-label 8 g extension study

 

Am J Hematol. 2012; 87(5):455-60. 

 

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell disorders which can progress to multiple myeloma. Therefore, they can be considered for studying multiple myeloma precursor disease and for developing early intervention strategies. Given the uncertainty of disease progression with MGUS and SMM, early intervention aimed at reducing the abnormal protein load and potential negative effects on the skeleton might be therapeutic. In the previous study based on 4 g of oral Curcumin in MGUS patients, showed decrease paraprotein load and bone resorption.

Objective:

To study the effect of Curcumin on serum free light chains and bone turnover in MGUS and SMM patients with a 4 g dose study and 8 g dose extension study. This in turn will help to determine whether a dose of 4 g or 8 g would provide benefit to patients with myeloma precursor disease.

 

Study Design:

A randomized double blind placebo controlled cross-over 4 g study, followed by an open-label extension study using 8 g dose, was planned. Thirty six patients (19 MGUS and 17 SMM) were selected on the basis of elevated paraprotein level (>20 g/L), an abnormal free light chain ratio or both. Patients were randomized into two groups: one received 4 g Curcumin and other 4 g placebo, crossing over at 3 months. All patients were given the option of entering open-label 8 g extension study for further 3 months. Blood and urine samples were collected at baseline and specific intervals. Serum paraprotein, immunoglobulin-electrophoresis, serum calcium and serum B2 microglobulin were measured. FLC (Free light chain) levels and marker of bone turnover Urinary deoxypyridinoline (u-DPYD) were also measured. Group values were expressed as the mean ±1 standard deviation. Data from within the groups were compared using student’s paired t-test.

 

Results and Discussion:

  1. A total of 25 (16 MGUS and 9 SMM i.e. 69%) patients completed the 4 g cross-over study. Whereas, 18 patients completed the 8 g extension study.
  2. This was the first study to describe the beneficial effect of Curcumin on free light chains in MGUS and SMM patients. The results showed that Curcumin (4 and 8 g daily) decreased the free light-chain ratio (rFLC, -35 and -36 %), involved free light-chain (iFLC, -8 and -10 %) and difference between clonal and nonclonal light-chain (dFLC, -9 and -11 %) in both MGUS and SMM patients.
  3. The baseline rFLC was an important variable affecting the response to Curcumin supplementation. Patients were divided into two groups: one with abnormal rFLC at baseline and other with normal rFLC at baseline. Patients with abnormal ratio at baseline showed a greater response (decrease) in their ratios as compared to those having normal rFLC ratio at baseline.
  4. Curcumin therapy also showed the reduction in total serum protein and random urinary protein concentrations.
  5. Excretion of uDPYD (a marker for bone resorption) was also found to decrease after Curcumin supplementation.

 

Conclusion:

The study showed that Curcumin may benefit some patients with MGUS or SMM. More benefit was seen in case of patients having abnormal FLC at baseline and increased benefit was seen for the higher dose of 8 g/day. None of the patient showed progression to active disease one year after the study was complete. 

These findings suggest that Curcumin have the potential to slow the disease progression and can be used to plan intervention strategies in patients with MGUS and SMM. However, larger studies are needed to assess the role of Curcumin in patients at risk of transformation.

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