Is it Safe to Take Curcumin for Cancer During Chemotherapy?

The term cancer is used to define a group of disorders characterized by a nonproliferative growth of cells. The cells multiply rapidly and spread to different tissues all over the body. [1]

The disease is treated through chemo or radiotherapeutic methods. However, the former is preferred as it is cheaper and has fewer side effects on the body as opposed to the treatment of tumors with strong ionic radiations.

Chemotherapy comes with its drawbacks: at times it is not effective as the cancer cells are not sensitive to it and it may pose a danger to the normal cells surrounding the cancerous growths.

To overcome these, scientists are taking significant effort to find a compound which could be used in combination with this treatment and produce positive results. [2]

Curcumin, with its multi-targeting system and natural origin, possesses ideal properties to fulfill this need.

Several studies have been conducted to assess the safety and efficacy of curcumin based formulations with chemotherapeutics.

The results of such endeavors have proven to be fruitful, prompting for further investigations for its application. [3]

What is Curcumin?

Curcumin is a naturally yellow compound which is an essential component of the spice, turmeric. It has been used throughout history as it is believed to display excellent healing properties.

It is highly bioactive and polyphenolic in nature, and its administration elicits several positive effects on the human body.

Medical professionals often refer to the compound as ‘curcumin’ as it is capable of fighting and reversing signs of almost any disease.

Curcumin & Drug Metabolism

Curcumin has a unique multi-targeting system that helps it monitor many different types of cellular activities.

The nutrients present in it have the ability to control the rate of cell division and fix cell damage.

This may be the reason it has become a popular compound for cancer studies. Another naturally occurring useful chemical is piperine, a bioactive extract of black pepper. [4]

Piperine and curcumin are often used in combination with one another as the former has been seen to enhance the absorption and bioavailability of the latter to the extent of up to 154%.

This phenomenon has been seen to be valid in animal and human models with no side effects. [5]

This was analysed in depth by Suresh D in 2010. He studied how oral administration of curcumin, piperine, and capsaicin (derived from turmeric, black pepper, and red pepper respectively) affected animals.

The main parameters being analysed were tissue distribution and elimination of these compounds. His most notable finding was the improved bioavailability of curcumin when coupled with piperine. [6]

Curcumin and piperine are known to interact with administered drugs and regulated their metabolism and availability to surrounding tissues. This is where they would come in handy for chemotherapeutic metabolism.

This property of the dyad was determined by the 2006 Canadian journal of physiology and pharmacology study which highlighted how the same three compounds used above (curcumin, piperine, and capsaicin) could regulate rat liver metabolism.

The results were obtained both in-vivo and in- vitro showing the effects of piperine, in particular on various metabolic pathways. This indicates a potent drug regulatory ability of the compound. [7]

Following this, scientists attempted to better understand the pharmacokinetics of curcumin and piperine. They studied their interaction with other conventional medicines, midazolam, flurbiprofen, and paracetamol.

However, the limited bioavailability of curcumin posed a hindrance to its drug modulating capabilities as was seen when attempts were made to use it to enhance heme oxygenase activity as well. [8][9]

More work on delivery systems for the compounds would aid its application in drug regulation.

Given the excellent anti-inflammatory and anti-oxidant effects the compounds elicit, such endeavors would prove to be very fruitful for boosting the effects of chemotherapy. [10]

What does this mean?

Curcumin and piperine work well together as piperine helps in elevating the bioavailability of curcumin while they monitor drug metabolism in body tissues.

Curcumin & Activity of the Chemotherapeutic Drug

Chemotherapeutics, though effective may at times pose harm to other body cells or at times, may not eliminate tumors to their full potential.

Extensive research has shown the advantages that curcumin provides in overcoming these hurdles to cancer treatment.

Some studies focused on using curcumin with standard chemotherapy drugs are listed as follows:

1. Adriamycin

Adriamycin is a commonly used cancer drug given its ability to halt the growth of tumors of various types and origins.

However, it comes with its own set of drawbacks. It has been observed that the drug induces cardiotoxicity with prolonged use.

Curcumin provides a solution to this problem. As shown by Narayan Venkatesan’s animal model experiment, curcumin protects from the harmful effects of Adriamycin.

Through exertion of its strong anti-oxidant abilities, it blocks free radicle mediated toxicity, targeting key enzymes like creatine kinase (CK) and Lactate Dehydrogenase (LDH). [11]

What does this mean?

Curcumin;’s free radicle mediating property makes it useful for combinatorial therapy with Adriamycin and preventing organ injury in the process.[12]

2. Cisplatin

A common barrier while using cisplatin for cancer treatment is that the malignant cells can be immune to the treatment. Therefore, they need to be sensitized. This can be achieved through usage of curcumin.

Curcumin has been seen to be able to increase cisplatin sensitivity in laryngeal carcinoma and lung cancer cells. It was able to aid cisplatin to limit metastatic growth and induce cell death.

In addition, cancer related genetic pathways were controlled and free radicles were eliminated owing to cisplatin’s chelating activity. [13][14]

What does this mean?

Curcumin regulates cancer cell properties to make them more sensitive to treatment with cisplatin.

3. Doxorubicin

The use of doxorubicin in cancer patients is often accompaniedby a decrease in quality of life (QOL). This can be countered by suitable food supplementation.

A 2012 International Journal of Pharmaceutics experiment brought to light how curcumin could upgrade the effects of doxorubicin.

Together, the compounds could bring about apoptosis and lower cancer cell viability. Cucrumin also played an instrumental role in doxorubicin mediated inhibition of the caspase pathway (an integral cancer development mechanism). [15]

What does this mean?

The doxorubicin- curcumin mixture has a lot of potential for future chemotherapeutic applications. They block tumour forming signals effectively and in turn, bring about cell death.

4. 5- Flourouracil

Antimetabolites such as 5- Flourouracil comprise some of the first effective chemotherapeutics to be discovered.

While they can control cell proliferation, they often cause cytotoxicity in cells surrounding the solid tumour.

Ferguson and Orlando attempted to overcome this hurdle to treatment by combining curcumin with 5-FU in a human breast cancer model.

Through complex cell viability assays they determined that this combination was highly beneficial. Along with preventing the multiplication of cancer cells, curcumin protected normal cells from the detrimental impacts of 5-FU. [16]

What does this mean?

Curcumin, when combined with 5-FU reduces the impact of its cytotoxic effects on cells. This could promote higher dosage or longer treatment durations with the drug.

5. Oxaliplatin

Although oxaliplatin displays high efficacy as a chemotherapeutics, its use is also accompanied with toxic effects on the patient. This could be a source of discomfort and could dissuade from treatment.

Curcumin could aid in preventing such effects. This was seen when the compound was used along with 5-FU and oxaliplatin to treat gastric cell cancer. The results were validated both in-vivo and in- vitro.

The cancer cell proliferation was blocked by downregulation of the expression of Bcl-2 protein and mRNA and upregulation of Bax and caspase 3, 8, and 9. [17]

What does this mean?

By modulation of protein expression, curcumin could induce apoptosis in cancer cells when used along with 5-FU and Oxaliplatin.

6. Paclitaxel

Paclitaxel is a chemotherapeutic commonly used for breast cancer or ovarian cancer. It works through inhibition of mitosis i.e. reduction in cell division.

Two studies have highlighted how thesynergistic activity of curcumin and paclitaxel could provide benefits to breast cancer therapy.

The first one illustrated how the curcumin-paclitaxel combination could inactivate a key carcinogenic signal- NF-kappaB.

The experiment carried out on a mouse model showed great promise for the dyads further chemotherapy applications as they were capable of deactivating NFKB successfully and in turn, causing cell death. [18]

The second study delved deeper into the numerous genetic reactions that could be controlled by this combination. The key takeaway from this research was that curcumin and paclitaxel were instrumental in blocking key cancerous proteins- NFKB and Bcl-2. [19]

What does this mean?

When curcumin and paclitaxel are used together for cancer treatment, they effectively block some of the main proteins responsible for cell proliferation.

Should you Avoid Curcumin with Chemotherapeutic Drugs?

The above statement may seem confusing given the many benefits that have been listed previously.

While there is scientific evidence boasting of the benefits of curcumin and chemotherapeutic drugs, there are several factors to consider before one begins its regular use.

Some researchers feel that curcumin’s mechanism is still unclear to recommend its use

Firstly, cancer is a highly complicated disease. There are a large number of cell processes, pathways, and interactions involved in its development and progression.

Compounds like curcumin are employed to treat it as they have high anti-inflammatory and antioxidant capacities.

However, the scientist Sarah Crawford recently hypothesized that many of these drugs, in an attempt to block cancer cycles are targeted at establishing an equilibrium within cells which should halt their proliferation.

Over time, disturbances in this equilibrium may be the cause of recurrence of the disease. [20]

The number of proteins, metabolites, and cellular signals it alters is vast, and their long-term implications- recurrence of disease, side effects remain unknown. [21]

It is therefore essential for doctors to maintain caution when suggesting its use to patients. They must fully inform them of the risks involved, possible side effects and regulations to be followed.

Taking certain precautions may help increase the safety and efficacy of curcumin with chemotherapy

One must consult a doctor before taking curcumin for cancer treatment. The dose of curcumin matters: for example, curcumin at low doses serves as an antioxidant while at high doses serves as a prooxidant.

It is also essential, to begin with, smaller doses and maintain a minimum of 3-4 hours gap between drug consumption and curcumin supplementation.

The reason for this is the drug metabolizing activity of the compound which may lead to undesirable reactions within the body. [22]

Since curcumin boosts the action of chemotherapeutic drugs, it is necessary to inform the health practitioner as this may require altering chemotherapeutic drug doses.

Diet and disease are known to have a direct relationship with one another.

Therefore, proper regulation of the natural products we consume is essential to maintain good health and keep ourselves fighting fit.

Dosage

A specific dosage of curcumin has not been prescribed for combination with chemotherapeutics.

However many studies utilize a dose of 300mg twice a day for such conditions. [23]

Read: Curcumin Dosage in Cancer

Most research studies utilise a dose of 500-1000mg of curcumin per day. It is best to consult a doctor for the appropriate dosage and formulation of curcumin.

The most commonly used curcumin supplements are standardized 95% curcumin extract with bioperine. Curcumin requires piperine or fats for absorption.

However, you can go through other curcumin supplement formulations here that aid in increasing bioavailability of curcumin.

Read: Best Curcumin Supplements

Always start with a low dosage and increase gradually over weeks. Curcumin supplements are best taken after meals and avoid taking them at the same time as any other medication. Maintain a 3-4 hour gap.

Precautions

Turmeric in diet is safe and most studies have demonstrated that curcumin, even at high dosages, is safe.

However, a few precautions must be noted

• Rule out any allergies with turmeric and curcumin.
• Avoid taking curcumin supplements on an empty stomach as they may trigger acid reflux in susceptible individuals.
• Gastric discomfort is possible with the sudden introduction of curcumin, especially at high doses. Start with small dosages and increase gradually over weeks to recommended dosages to minimise gastric side effects.
• In case of serious gastric side effects, discontinue usage of curcumin.
• Curcumin interferes in drug metabolism. Hence it is advised to avoid taking curcumin supplements at the same time as taking other medicines.
• Maintain a 3-4 hour gap. Also, consult a health practitioner with regards to this to avoid any drug interactions.
• Curcumin has blood thinning activity. If taking blood thinners or suffering from a bleeding /clotting disorder it is advisable to avoid curcumin supplements in this case. Consult a health practitioner with regards to this.
• Discontinue curcumin supplements 2 weeks prior to surgical procedures to avoid bleeding risk.
• If suffering from gallstones or bile duct obstructions, avoid curcumin supplements.
• Avoid turmeric supplements in pregnancy and lactation.
• Ensure that you opt for good quality curcumin supplements that are free from toxicity, heavy metal contamination, fillers or additives.
• It is best to take curcumin supplements with Bioperine or other agents that increase its bioavailability.
• Consult a health practitioner before taking curcumin supplements.

Conclusion

Through the above studies, we can see that curcumin offers a variety of benefits for cancer treatment when combined with other commonly used chemotherapeutics. But, it is still work in progress.

However, it must be understood that optimizing cancer therapy has been a 70+ yearlong endeavor with the struggle continuing. The markers and mechanisms of the disease are incredibly complex.

Bearing that in mind, caution must be exercised before applying any new or novel technique for treatment.