- CASE REPORT
Long-term stabilisation of myeloma with curcumin
- Correspondence toDr Abbas Zaidi, firstname.lastname@example.org
- Accepted 19 February 2017
- Published 16 April 2017
Myeloma is a haematological malignancy which typically follows a relapsing-remitting course. While treatment can control the myeloma and improve quality of life for given periods of time, remissions generally become progressively shorter with subsequent relapses, and patients ultimately enter a final refractory phase. To help control symptoms and enhance quality of life, some patients use complementary therapies as an adjunct to their conventional therapy. Here, we describe a myeloma patient who started a daily dietary supplement of curcumin when approaching her third relapse. In the absence of further antimyeloma treatment, the patient plateaued and has remained stable for the last 5 years with good quality of life.
Myeloma is a B-cell malignancy that is characterised by the monoclonal expansion and accumulation of abnormal plasma cells within the bone marrow. Clinical manifestations include bone pain, renal impairment, recurrent infections and anaemia.1 Over the past decade, advances in the understanding of the disease, together with the development of several novel treatments, have led to significant improvements in overall survival.2
Despite this, myeloma remains incurable, with a median overall survival of 5.2 years from diagnosis.3 The course of the disease is typically one of recurrent remission and relapse. However, patients progressively acquire resistance to treatment and subsequent remissions become shorter and shorter. Eventually, either they run out of treatment options or become refractory to them.
In an effort to improve long-term outcomes, some myeloma patients seek to use dietary supplements, mostly for palliative purposes. While they may help to improve quality of life, there is little evidence they can increase survival.4 Among them, curcumin, the active constituent of turmeric, has gained popularity as a complementary therapy in several cancers.
Here, we present a case of a heavily pretreated relapsing myeloma patient who, in the absence of further treatment options at the time, started daily curcumin and has since remained stable for the past 5 years.
A woman aged 57 years was initially diagnosed with monoclonal gammopathy of undetermined significance (MGUS) in 2007 following an incidental finding of M-protein (18 g/L) during investigation for hypertension.
Within 15 months, the patient had rapidly progressed to ISS stage 3 myeloma with M-protein 49 g/L, urinary protein 1.3 g/24-hour, Bence-Jones protein 1.0 g/24-hour, Hb 9.7 g/dL and increasing back pain. She initially declined antimyeloma treatment but 6 months later, following vertebral collapse at T5 and T12, started cyclophosphamide, thalidomide and dexamethasone (CTD) treatment. However, after a week, the patient was admitted with idiosyncratic syndrome including hyponatraemia, a fall in albumin and worsening of blood counts. She received red cell transfusion and her electrolyte abnormalities were carefully corrected.
Although there was evidence of a response to CTD (M-protein 34 g/L), bortezomib and dexamethasone treatment was initiated as an alternative, but this was discontinued after three cycles due to progressive disease (M-protein 49 g/L). The patient was then treated with lenalidomide and dexamethasone with the aim of reducing disease burden prior to high-dose therapy and autologous stem cell transplantation. Treatment was frequently interrupted and dose adjusted to account for neutropenia and despite a minor response after six cycles (starting M-protein 47 g/L, finishing M-protein 34 g/L), in October 2009, she proceeded with stem cell mobilisation. However, neither cyclophosphamide nor plerixafor/GCSF priming were successful. A bone marrow biopsy revealed 50% myeloma cells and a course of CTD was restarted with cautious titration of thalidomide.
The patient achieved a partial response with CTD retreatment over the course of 17 cycles (M-protein 13 g/L) with no further episodes of idiosyncratic syndrome. However, attempts to harvest stem cells in February 2011 and again there months later, both failed. By then, her M-protein had risen to 24 g/L and the patient was too neutropenic to be considered for a clinical trial.
At this point, the patient began a daily regime of oral curcumin complexed with bioperine (to aid absorption), as a single dose of 8 g each evening on an empty stomach. A few months later, she also embarked on a once-weekly course of hyperbaric oxygen therapy (90 min at 2 ATA) which she has maintained ever since. Her paraprotein levels gradually declined to a nadir of 13 g/L, her blood counts steadily improved and there was no evidence of further progressive lytic bone disease.
Outcome and follow-up
The patient continues to take oral curcumin 8 g daily without further antimyeloma treatment. Over the last 60 months, her myeloma has remained stable with minimal fluctuation in paraprotein level, her blood counts lie within the normal range and she has maintained good quality of life throughout this period. Repeat bone imaging in 2014 identified multiple lucencies <1 cm in the right hip and degenerative changes in both hips, but these were attributed to osteoarthritis rather than the myeloma. Recent cytogenetic analysis revealed she had no abnormal cytogenetics by fluorescent in situ hybridisation.
A small but significant number of myeloma patients consume dietary supplements in conjunction with conventional treatment primarily to help cope with the side effects of treatment, manage symptoms and enhance general well-being. Few, if any, use dietary supplementation as an alternative to standard antimyeloma therapy. Here, we describe a case in which curcumin has maintained long-term disease control in a multiply-relapsed myeloma patient. To the best of our knowledge, this is the first report in which curcumin has demonstrated an objective response in progressive disease in the absence of conventional treatment.
Curcumin is a polyphenol derived from the perennial herb Curcuma longa (turmeric) and has, for centuries, been used as a traditional Indian medicine. Several reports published over the two decades have claimed various health benefits of curcumin and this has led to its increasing popularity as a dietary supplement to prevent or treat a number of different diseases.5 ,6
The biological activity of curcumin is indeed remarkable. It is a highly pleiotropic molecule which possesses natural antioxidant, anti-inflammatory, antiseptic and analgesic properties.7 More recently, it has demonstrated antiproliferative effects in a wide variety of tumour cells including myeloma cells and exerts its antiproliferative effects through multiple cellular targets that regulate cell growth and survival.
In vitro, curcumin prevents myeloma cell proliferation through inhibition of IL-6-induced STAT-3 phosphorylation and through modulation of the expression of NF-kB-associated proteins such as IkB〈,Bcl-2, Bcl-xL, cyclin D1 and IL-68 and apoptosis-related molecules including p53 and Bax.9In other studies, curcumin was shown to circumvent resistance to dexamethasone, doxorubicin and melphalan as well as potentiate the effects of bortezomib, thalidomide10 and lenalidomide.11Furthermore, curcumin-induced cell death was not influenced by myeloma molecular heterogeneity.12
The antimyeloma effects of curcumin in the clinical setting however are less clear. Only one phase I/II study has evaluated curcumin treatment in myeloma patients. These patients were either asymptomatic, relapsed or had plateau phase disease. Treatment with curcumin downregulated the expression of NFkB, COX-2 and STAT3 in peripheral blood mononuclear cells, but no objective responses were observed in any subgroup of patients.13 This may be as a result of small sample size in this study, follow-up was limited to 3 months and clinical responses may have been observed with longer follow-up. However, downregulation of NFkB, COX-2 and STAT3 expression may not correlate with the clinical activity of curcumin and there may be further mechanisms of action that remain unclear, possibly through the modulation of another target. We would not be able to identify any patient-specific mechanisms of activity in this case study, as the patient has been taking curcumin for some time now and baseline bone marrow or peripheral blood samples are not available. However, in the setting of a clinical trial, it may be possible to use next-generation sequencing to help identify a mutation that may be a potential target for curcumin.
Another study examined its effects in preventing the progression of MGUS and smouldering myeloma to myeloma.14 ,15 The results showed that curcumin exerted a trace of biological activity with modest decreases in free light chain and paraprotein levels and a reduction in a marker of bone resorption with curcumin treatment, suggesting the therapeutic potential of curcumin in MGUS and smouldering myeloma. However, more studies are needed to address this further.
Whether such effects are observed in patients with active disease remains to be seen. The fact that our patient, who had advanced stage disease and was effectively salvaged while exclusively on curcumin, suggests a potential antimyeloma effect of curcumin. She continues to take daily curcumin and remains in a very satisfactory condition with good quality of life. This case provides further evidence of the potential benefit for curcumin in myeloma. We would recommend further evaluation of curcumin in myeloma patients in the context of a clinical trial.
Myeloma is a relapsing-remitting cancer for which there is currently no cure.
Curcumin, a polyphenol derived from turmeric, has been used for many years in some
We report a case of a myeloma patient with advanced myeloma who, in the absence of conventional treatment, plateaued and has remained stable for many years with daily curcumin.
Dietary supplements, such as curcumin, may be beneficial for some myeloma patients.
Twitter Follow Maggie Lai @MyelomaUK
Contributors AZ and JC involved in treating the described patient initially discussed and planned writing this case. The planning was made with ML of Myeloma UK. Each performed a review of the literature and a summary of the case was provided by AZ and JC to ML who wrote the initial draft. The final paper was edited by AZ and reviewed and edited by JC.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
How Dieneke Ferguson beat multiple myeloma with curcumin
With one year to live, Dieneke Ferguson beat multiple myeloma cancer using high dose curcumin after conventional treatment failed. And her case is documented in the BMJ!
In March 2007, at 57 years old, Dieneke Ferguson was diagnosed with monoclonal gammopathy of undetermined significance (MGUS), which developed into multiple myeloma (a type of blood cancer) by May 2008.
She underwent three rounds of chemotherapy, as well as four failed attempts to harvest stem-cells for a stem-cell transplant. During this time, she also lost her memory for three days.
In November 2008, two of Dieneke’s vertebrae collapsed, as a result of the myeloma. One vertebrae could not be repaired, and she lost 7 cm of height.
By May 2011, her future looked bleak, as no other traditional medical options were available. According to statistics at the time, her life expectancy was, at the very best, one more year.
Dieneke learned about the anti-cancer effects of high-dose curcumin from another myeloma patient/blogger named Margaret and in May 2011, she started taking high doses of curcumin (8g a day). This is the protocol used by the curcumin-myeloma clinical trial (2007) at the MD Anderson Cancer Research Center in Houston, Texas.
A few months later she began weekly hyperbaric oxygen therapy for 90 minutes at 2ATA.
Her paraprotein levels gradually decreased and her blood numbers steadily improved. Five years later she was reported stable with no progression of disease and normal quality of life. And she even carried the torch in the 2016 Rio Olympics!
Dieneke’s remarkable case was written up in the British Medical Journal, and was published in April 2017 – “Long Term Stabilisation of Myeloma with Curcumin.”
She is still alive and well today!
In May 2017, BBC4 Radio Food Programme produced a show on turmeric/curcumin and interviewed Dieneke and her consultant/co-author of the report, Prof. Jamie Cavenagh (Consultant Haematologist at London’s Barts Hospital). Dieneke’s interview starts at 22:30.
In January 2018, the British Medical Journal published its most read case studies of 2017, and Dieneke’s case study was second on the list.
Dieneke’s Curcumin Protocol
Dieneke took/takes Doctor’s Best C3 Complex Curcumin with BioPerine (1000mg tablets).
C3 Complex is a standardized curcumin extract that has been used in 45 human clinical trials. BioPerine is a extract from black pepper that increases curcumin absorption.
Dieneke took 8g (eight 1000 mg pills) all at once at night on an empty stomach. She is currently taking 9g per day.
The 8 gm per day protocol will cost roughly $100 per month. A 120 tablet bottle is currently $50 per bottle on amazon and will last two weeks. I think it makes sense to get six bottles, take high dose curcumin daily for three months and then get your blood work checked to see if there’s improvement.
To prevent any adverse reaction, it is recommended that you gradually increase the curcumin dose over four weeks, doubling each week, until you get to 8 grams per day, which is what Dieneke did.
Week 1: 1 gram per day
Week 2: 2 grams per day
Week 3: 4 grams per day
Week 4: 8 grams per day
*1 gram is one 1000 mg tablet. If you buy 500mg tablets instead of 1000mg tablets, you will need to take twice as many.
Multiple human clinical trials have demonstrated that 8 grams of curcumin per day is generally safe, and this study demonstrated that 12 grams of C3 Complex can be taken per day with out adverse effects.
However, for a high dose protocol such as this I would rotate between several brands of C3 Complex with Bioperine such as Doctor’s Best, Pure Encapsulations, and Designs for Health as they are more cost effective.
You might also like this post: How Mona healed multiple myeloma without conventional therapy.
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