5 Proven Benefits Of Curcumin （Curcuma Longa) For Multiple Myeloma
By Dr. Wangchuk (BBEbiotech)
Multiple myeloma is a type of blood cancer in which the plasma cells become malignant.
The plasma cells are derived from the B cells (B lymphocytes) of the white blood cells, formed in the bone marrow (spongy tissue inside some bones of the body like hip, skull, femur, rib cage etc).
The plasma cells are an important component of the immune system as they produce antibodies to fight infections.
In the case of multiple myeloma, these cells multiply abnormally and cause multiple tumour formation in many bones of the body. As a result, the healthy blood cells formation is impeded in the bone marrow.
The tumours can also cause weakening of the bone by breaking down the bone tissue and releasing calcium into the blood. The elevated calcium levels in the blood may affect other organs as well such as kidney, heart, digestive tract, muscles, and nerves.
The cause of this disease is unknown.
However, the mutation in the plasma cell DNA due to some genetic, chemical or environmental factors is thought to be a major cause.
The symptoms of this disease include bone problems, anaemia (causing weakness, breathlessness), high blood calcium levels in the blood (causing extreme thirst, loss of appetite, frequent urination, abdominal pain etc), kidney problems, recurrent infections (especially pneumonia) etc.
Multiple myeloma can give rise to a condition called amyloidosis due to build up of certain proteins. This can lead to purple spots on skin, swelling, diarrhoea, numbness in feet and legs etc.
The risk factors that are involved in the development of multiple myeloma are older age, exposure to radiations or certain chemicals, history of diseases like MGUS (high levels of M. Protein in the blood) and plasmacytoma (a cancer of plasma cells). Also, this disease is found to be common in males.
The treatment of this disease involves chemotherapy, radiotherapy, surgery, targeted therapy etc. The corticosteroids are also sometimes employed. Stem cell transplant is another emerging treatment option.
However, these treatment methods generally have several drawbacks due to the side-effects (nausea, organ damage, low blood count etc), high cost or limited access to these.
The limitations of conventional treatment approaches call for natural alternatives. A natural product that can be useful in the treatment of multiple myeloma is curcumin.
What is curcumin?
Curcumin (diferuloylmethane) is a polyphenolic compound present in the roots of Curcuma longa. This compound is responsible for the yellow-orange colour and it is the most biologically active component of Curcuma Longa.
Curcumin has the ability to modulate a number of molecular pathways of a living cell resulting in therapeutic benefits.
The modulation of various molecular pathways by curcumin confers it anti-inflammatory, antioxidant, antimicrobial, anti-cancer, immune-modulatory and many other properties.
These properties have medicinal value in numerous diseases such as diabetes, infections, kidney problems, heart problems, cancer, Alzheimer’s etc.
5 Proven Benefits of Curcumin in Multiple Myeloma
The anti-cancer activity of curcumin is effective against almost all types of cancer, including multiple myeloma. Curcumin has a therapeutic action on various aspects of this disease, from treatment to prevention.
1. Curcumin kills multiple myeloma cells
The development of multiple myeloma is primarily a result of activation of oncogenes (genes having the potential of causing cancer). The survival and proliferation of the cancer cells depend on various cytokines and other survival pathways. https://www.ncbi.nlm.nih.gov/pubmed/12965277
Curcumin has the capability of inducing apoptosis/ cell death in the multiple myeloma cells. It does so through its action on various molecular pathways involved in cancer development and survival.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758121
Curcumin is known to induce apoptosis in the myeloma cells by down-regulating the expression of Mcl-1 (involved in cancer survival).
https://www.ncbi.nlm.nih.gov/pubmed/25517601
It also down-regulates the proteins like survivin and Bcl-2 (involved in cancer survival) and up-regulates Bax proteins (activate apoptosis). This helps in killing the multiple myeloma cells and inhibiting their proliferation.
Curcumin has the ability to enhance the activity of p53 protein (a tumour suppressor protein) that promotes the apoptosis process.
https://www.ncbi.nlm.nih.gov/pubmed/17708799
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356419/
The suppression of the proliferation of multiple myeloma cells by curcumin is also attributed to its inhibitory action on the constitutive STAT3 phosphorylation induced by IL-6 (a process involved in the development of cancer by activating oncogenes).
https://www.ncbi.nlm.nih.gov/pubmed/14500688
Curcumin inhibits the expression of NF-kappa B gene as well. This leads to the inhibition of the gene products of this gene that are involved in cancer development and survival such as Bcl-1, Bcl-x, IL-6, etc. This leads to inhibition of proliferation and arrest of the cell cycle causing cell death.
https://www.ncbi.nlm.nih.gov/pubmed/12393461
What does it mean? It means consumption of curcumin can kill the multiple myeloma cells and suppress their proliferation. The inhibition of factors involved in cancer survival and the activation of the pro-apoptotic factors by curcumin helps in this.
2. Curcumin inhibits angiogenesis
Just like other cancer types, multiple myeloma is also characterized by increased angiogenic activity. This disease is developed due to enhanced angiogenesis (development of blood vessels) in the bone marrow.
The pro-angiogenic factors are expressed more and anti-angiogenic factors are suppressed resulting in an aberrant development of blood vessels which supply the cancer cells with oxygen and nutrients.
The involvement of various growth factors is seen in the process of angiogenesis in multiple myeloma. These include VEGF (vascular endothelial growth factor), bFGF (basic fibroblast growth factor), BDNF (brain derived neurotrophic factor) etc.
https://www.ncbi.nlm.nih.gov/pubmed/21735169
https://www.ncbi.nlm.nih.gov/pubmed/10942925
Curcumin has been found to have an anti-angiogenic effect as well. It can inhibit angiogenesis by acting on the signal transduction pathways that promote angiogenic activity.
https://www.ncbi.nlm.nih.gov/pubmed/17569211
It is known to inhibit the activity of bFGF significantly in an animal model.
Curcumin also inhibits BDNF production in the multiple myeloma cells, which in turn prevents the induction of angiogenesis.
https://www.ncbi.nlm.nih.gov/pubmed/10780880
https://www.ncbi.nlm.nih.gov/pubmed/16584595
What does it mean? It means curcumin can help in prevention of the development of multiple myeloma by inhibiting angiogenesis. Also, angiogenesis can be targeted by curcumin in order to treat the disease.
3. Curcumin overcomes drug-resistance in multiple myeloma cells
Multiple myeloma is a very challenging disease to treat due to a high probability of developing resistance to the drugs used in its treatment.The anti-apoptosis mechanisms and abnormal drug transport are primarily responsible for this.
The over-expression of proteins related to MDR (multi-drug resistance) genes is found to be strongly linked to the drug resistance in the multiple myeloma cells.
The faulty action of p53 gene products also results in prevention of apoptosis and promotes the drug resistance.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926819/
Thalidomide and bortezomib are the most commonly used chemotherapeutic drugs against multiple myeloma and resistance to which is frequently observed.
Curcumin has been found to reverse the drug resistance to many drugs in the drug-resistant cells of multiple myeloma through various mechanisms.
It can induce apoptosis in the cells by preventing damage repair to the DNA of the multiple myeloma cells.
https://www.ncbi.nlm.nih.gov/pubmed/19756599
Curcumin increases the toxic effect of the drug bortezomib on the multiple myeloma cells by interacting with NF-kappa B gene and by enhancing the proteasome inhibiting activity of the drug.
https://www.ncbi.nlm.nih.gov/pubmed/22606012
In many studies, a combination of curcumin with bortezomib has been found to have synergistic effect in inducing apoptosis in the multiple myeloma cells, thus, potentiating the action of the drug.
https://www.ncbi.nlm.nih.gov/pubmed/21729550
https://www.ncbi.nlm.nih.gov/pubmed/19383353
Curcumin has also been found to synergistically act on multiple myeloma cells with the drug thalidomide.
https://www.ncbi.nlm.nih.gov/pubmed/23784627
What does it mean? It means supplementation of curcumin with other chemotherapeutic drugs can be useful in overcoming the drug-resistance in the multiple myeloma cells. Action of curcumin helps in inducing apoptosis and enhances the activity of the chemotherapeutic drugs.
4. Curcumin has chemopreventive action against multiple myeloma
Being a nearly incurable disease, prevention is the best cure for multiple myeloma. Prevention of cancer or for that matter any disease can be achieved through diet, as there are plenty of phytochemicals that have chemopreventive properties, i.e. these compounds can prevent the development of cancer in the body.Curcumin is one such phytochemical with extraordinary chemopreventive action.It can protect against a number of cancers (including multiple myeloma) by virtue to its anti-cancer activities, such as induction of apoptosis, inhibition of angiogenesis and metastasis.
Moreover, curcumin has the ability to suppress the biological activation of carcinogens (cancer-causing agents) as well that helps in prevention of cancer.
https://www.ncbi.nlm.nih.gov/pubmed/17569209
The anti-inflammatory, antioxidant and immune-modulatory activities of curcumin have great implication in the prevention of cancer. These activities aid in overcoming adverse situations that can promote cancer development. Many studies have assured the efficacy of curcumin in chemoprevention of various types of cancers, including multiple myeloma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693758/
https://www.ncbi.nlm.nih.gov/pubmed/20726007
What does it mean? It means curcumin’s regular consumption can enable the body to combat the situations that may be potentially cancer causing. The anti-cancer, anti-inflammatory, antioxidant and immune-modulatory actions of curcumin help in this.
5. Curcumin protects from the side-effects of chemotherapeutic drugs
Most of the chemotherapeutic drugs, i.e. the drugs used for the treatment of cancer, pose serious side-effects to the patient. These side-effects can be life-threatening due to severe damage to vital organs such as kidney, lungs, heart, nerves, etc. Some of the commonly used drugs for the treatment of multiple myeloma are bortezomib, thalidomide, doxorubicin, etc.
Bortezomib is known to damage sensory neurons that results in
severe peripheral neuropathy. It also causes cardiotoxicity, i.e. damage to heart cells.
https://www.ncbi.nlm.nih.gov/pubmed/25588865
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906186/
In the patients of multiple myeloma, Bortezomib has been found to cause damage to the lungs causing respiratory problems.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774611/
Thalidomide causes mild toxicities like neuropathy, headache, skin rash, constipation, etc.
https://www.ncbi.nlm.nih.gov/pubmed/15327481
Doxorubicin is also known to cause severe side-effects such as those of cardiotoxicity, hepatotoxicity, gastrointestinal dysfunction, etc.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116111/
Curcumin is a compound that is fatal to the cancer cells but at the same time, it protects the normal cells of the body from the damage induced by the chemotherapeutic drugs.
https://www.ncbi.nlm.nih.gov/pubmed/20924967
It has been found to exert neuroprotective benefits in the neurotoxicity induced by the chemotherapeutic drugs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615942/
The antioxidant activity of curcumin has a cardioprotective effect against the damage induced by drugs like doxorubicin to the heart cells. It is also capable of attenuating the damages to the lungs and kidneys induced by doxorubicin.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271544/
https://www.ncbi.nlm.nih.gov/pubmed/19459743
Curcumin can ameliorate the damage to the stomach caused by chemotherapeutic treatment as well. It does so by preventing the apoptosis induced by the drugs in the normal intestinal cells. This is useful in improving the side-effects like nausea, vomiting, etc.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816802/
What does it mean? It means consumption of curcumin can protect the body tissues and vital organs from the side-effects of the chemotherapeutic drugs. This is useful in preventing a number of mild to severe side-effects.
Dosage of Curcumin For Multiple Myeloma
There is no specific dose of curcumin formulated for multiple myeloma.
However, most of the clinical trials on multiple myeloma patients have utilized dosage up to 12g of curcumin per day. These doses have been efficacious against the disease and well-tolerated by the patients.
Also, read Curcumin Dosage for cancer to get details on the accurate cycle for multiple myeloma. If looking for a maintenance curcumin dose for smoldering myeloma 8g of curcumin per day is advised.
Curcumin supplements are mostly normalized 95% curcumin with bioperine.
The amalgamation of curcumin with piperine and natural fats improves its bioavailability in the body.
Curcumin intake is better done after meals. Also, its consumption should follow a gap of at least 3-4 hours before taking a medication.
