The Most Exciting AntiCancer Botanical?
A terrific summary article by: Integrative Oncologist, Brian D. Lawenda MD, Integrative Oncology Essentials, Mar 2013
Curcumin is one of the hottest plant polyphenol extracts being researched, today. Until recently, I was unaware of the extensive history of curcumin research…dating back over 170 years! In the last 10-years, alone, there have been over 4,600 scientific papers published on curcumin. Many of these studies suggest that this compound could be useful in the prevention and treatment of a wide spectrum of medical conditions and physiologic processes (i.e. cancer, inflammatory diseases, cystic fibrosis, Alzheimer’s disease, etc.)
Curcumin is derived from the roots of Curcuma longa, a member of the ginger family. Curcumin is the major component of the Indian spice turmeric, and is responsible for giving turmeric its bright orange-yellow color.
Why Do I Love Curcumin?
Most pharmaceutical drugs are designed to work only a single target (i.e. a cellular receptor, gene, protein, etc.) or physiologic pathway (i.e. inflammation, glucose metabolism, immune modulations, etc.) However, the more we learn about cancer, the more we recognize that in most cases each cancer is driven by a complex array of hundreds-to-thousands of targets and pathways. It is due to this complexity that (aside from some rare exceptions), scientists have been unable to discover a “silver bullet” cure for most cancers.
What Targets and Pathways Does Curcumin Hit?
Figure 1 shows how curcumin hits multiple targets and pathways that are critical for cancer survival and growth. Most drugs (colored ‘light blue-green’ in the figure), on the other hand, only hit single targets. To me, this figure clearly shows why I consider curcumin to be one of nature’s wonder ‘drugs.’
Below is a summary of some of the more important anti-cancer activities of curcumin:
- Inhibition of cancer cell division
- Increases cancer cell death
- Decreases cell growth
- Inhibition of cell survival
- Inhibits growth of blood vessels to tumors
- Decreased metastasis
- Inhibition of carcinogens
Curcumin Inhibits NF-kB
Perhaps one of curcumin’s most important activities is its ability to inhibit activation of NF-kB, a potent driver of chronic inflammation. NF-kB is a protein that acts as a crucial switch, turning on inflammation by activating genes involved in the production of inflammatory compounds. As NF-kB activation has been implicated in almost every stage of cancer development, progression and recurrence (as well as playing a key role in most chronic diseases), blocking this protein has tremendous health implications.
Curcumin Acts Synergistically With Chemotherapy and Radiation Therapy:
- Increases tumor cell sensitivity to chemotherapy and radiation therapy
- Protects normal tissues (liver, kidney, mucous membranes, heart, etc.) from radiation and chemotherapy injury
- One recent study demonstrated a significant reduction in radiation dermatitis (skin inflammation) in patients who received curcumin during their radiation therapy for breast cancer. Patients received either oral curcumin (2 gram tablets, taken 3 times per day) or a placebo. The authors reported that the patients taking the curcumin had dermatitis reactions that were on average 31% less than those taking placebo. One of the most impressive findings in this study was that the women taking curcumin had a marked reduction in their risk of developing severe skin reactions (called “moist desquamation”) compared with those taking the placebo; 28.6% (curcumin) versus 87.5% (placebo).
Preclinical studies have found that curcumin is able to inhibit the development of chemically-induced cancers of the:
Human studies have shown that curcumin (up to 8 grams per days for three months) is able to to reduce the progression of precancerous lesions of the:
- mouth (leukoplakia)
- cervix (high grade cervical intraepithelial neoplasia)
- skin (squamous carcinoma in situ)
- stomach (intestinal metaplasia)
Curcumin has been shown to have anti-cancer activity against numerous cancer types in preclinical studies (see Figure 2)…and unlike most conventional therapies, curcumin is completely non-toxic to normal cells.
To date, most of the clinical studies on curcumin have been “phase 1 trials,” which were designed to determine the bioavailability, safety, and early evidence of the efficacy of curcumin. One study demonstrated that curcumin is poorly absorbed across the bowel and into the systemic circulation, but is able concentrate in intestinal tumors quite well (in patients with advanced colorectal cancer who took 3.6 grams/day of curcumin orally for seven days.)
- If curcumin is so poorly absorbed into the blood, how could it be effective outside of the gastrointestinal tract? (Read the “epigenetic modulation” section, below, for one hypothesis.)
In a “phase 2 trial” (designed to investigate the effectiveness of curcumin in larger numbers of people, and to further evaluate its short-term side effects and safety) of patients with advanced pancreatic cancer, investigators reported some anti-cancer activity (albeit limited.)
- Read a nice review of this study by Tina Kaczor, ND, FABNO (11/2010)
Other phase 2 trials with curcumin are either completed or actively recruiting patients with breast cancer, colorectal cancer, pancreatic cancer, and head and neck cancer.
Epigenetic changes (also known as “modulation”) are changes to DNA that are due to either the addition of chemical groups (i.e. DNA methylation) or protein modifications (i.e. histone modifications) that impact how the DNA is processed. Epigenetic changes, such as these, can make it very easy or very hard to turn on or off various genes.
- Anti-cancer epigenetic changes are those thatturn off (or impair the function) of cancer promoting genes, or those that turn on cancer inhibitory genes.
In addition to all of the anti-cancer mechanisms illustrated in Figure 1 (above), new research suggests that curcumin (and other botanical compounds: EGCG, resveratrol, genistein, etc.) exerts some of its biological activities through anti-cancer “epigenetic” modulation. Investigators hypothesize that epigenetic modulation may help to explain how curcumin is able to affect so many biological processes despite the fact that curcumin is poorly absorbed into the systemic circulation. Epigenetic modifications only require very small concentrations of a compound to have a significant impact on gene expression.
- I know this is a difficult subject to understand. If you want to know more about epigenetics, watch this excellent 13 minute video to further explain the concept (“Our lifestyles and environment can change the way our genes are expressed.” NOVA ScienceNow)
Risks, Side Effects and Interactions:
Curcumin is considered to be a safe supplement, food additive and spice (by the U.S. FDA.) That said, there are still potential side effects, drug interactions and contraindications that you should know about:
- Doses up to 10g daily of curcumin have not been found to be associated with any signs of toxicity.
- Curcumin may cause an upset stomach. Dosages of 6g daily have been associated with minor flatulence and a yellowing of the stool.
- There is a risk of exacerbating existing gallbladder disease.
- May cause uterine stimulation (caution is recommended during pregnancy)
- May increase the risk of bleeding (due to platelet inhibition) when combined with other medications or botanicals such as, aspirin, anticoagulants (blood thinners), antiplatelet drugs, non-steroidal anti-inflammatory drugs, Gingko biloba, garlic, saw palmetto.
- May decrease the effectiveness of cyclophosphamide and camptothecin.
- Curcumin may also interact with drugs that are metabolized by the cytochrome P450 enzymes. Check this list of drugs that are also metabolized by cytochrome P450 enzymes.
- Patients with gastrointestinal disorders or predisposed to kidney stone formation should also use this supplement with caution.
How Do You Take It?
- Oral curcumin is poorly absorbed from the bowel. However, the absorption of curcumin can be increased when administered with piperine (an extract from black pepper.) Simply adding piperine to curcumin has been shown to increase curcumin absorption by 2000%!
- Newer formulations of curcumin are available with greater absorption characteristics (i.e. complexed with piperine, nanoparticles, liposomal formulations, etc.)
- Taking curcumin with meals can increase its absorption (especially fatty/oily foods: olive oil, avocado, fish oil, milk, seeds, etc.)
- Curcumin is rapidly cleared from the blood (within 1-4 hours of ingestion, most of it is cleared.) To maintain blood levels of curcumin, it is best to take it in divided doses throughout the day. Dr Andrew Weil recommends taking it three times per day.
- Dosage: Unfortunately, we don’t know the optimal dosing. That said, doses from 500-3600 mg of curcumin per day have been used in recent studies. For cancer prevention: 400-500 mg per day (The “Curcumin Guru,” Dr Bharat Aggarwal, says he takes 500 mg per day.) During and after cancer treatment: 800-3000 mg per day (divided dose, with meals.)
- If you want to take turmeric instead of curcumin, how much turmeric powder would you need to take per day? 1 tablespoon of dried turmeric powder weighs 6.8 grams. The average amount of curcumin (by weight) in turmeric powder is 3.4%. So, 1 tablespoon of turmeric powder is equal to 6.8 grams x 3.4% = 0.231 grams or 231 milligrams. Therefore, if you want to take 500 milligram of curcumin per day, you will need to consume approximately 2 tablespoons of dried turmeric powder.
- As with any supplement, please first discuss your interest in using curcumin with your oncology team before you start taking it.
Is Whole Turmeric More Potent Than Curcumin Extract?
In a personal communication with Dr Bharat Aggarwal, he shared with me some of his unpublished research that helps to shed some light on this question. (As with all unpublished data, it is important to await the results in a peer reviewed journal.)
His researchers implanted a colon cancer tumor into the intestines of a group of mice, waited for 7 days (for the tumors to grow) and then gave the mice (by mouth) either turmeric (at a dose of 0.1 g/kg per day) or curcumin (at a dose of 1 g/kg per day) for 28 days. The curcumin and turmeric were administered with extra virgin olive oil to improve their absorption. To test the possibility of synergy with chemotherapy, he also tested a separate group of mice with eitherolive oil (“vehicle”), curcumin, capecitibine (a commonly used chemotherapy agent) or curcumin with capcetibine. The mice were euthanized on day 29 and autopsied to measure the tumors.
He repeated the same experiment with a different group of mice, but this time implanted a pancreatic cancer tumor in the mice. He also tested for possible synergistic effects with another commonly used chemotherapy, gemcitibine, employing the same design: olive oil, curcumin, gemcitibine, gemcitibine with curcumin. (results not shown for space constraints)
- Both turmeric and curcumin suppressed the growth of the implanted colorectal and pancreatic cancers however, the turmeric dose required to suppress growth was1000% smaller than the curcumin dose!
- The combination of curcumin with the chemotherapy drugs was the most effective in slowing tumor growth for both colon and pancreatic tumors (this demonstrates the synergistic effect.)
Both curcumin and turmeric have significant anti-cancer activity against colon and pancreatic cancer in this preclinical study. Curcumin acts synergistically with two commonly used chemotherapy drugs for colon and pancreatic cancers. These data are exciting and if you are undergoing cancer treatment they are worth sharing with your cancer care team to see if taking curcumin or turmeric makes sense and is safe for you.
Curcumin (Linus Pauling Institute)
Curcumin Research (curcuminresearch.org)
Curcumin (research review and references; Examine.com)
Curcumin and Cancer Research (Ajay Goel, PhD, director of epigenetics and cancer prevention at Baylor Research Institute discusses research and controversies surrounding curcumin; 15 minute audio interview by Karolyn A. Gazella, May 2012.)
Turmeric and Frankincense in Inflammation: An Update (Study examines botanical remedies as treatments for various inflammatory conditions; by Jeremy Appleton, ND, September 2011.)
Prevention and Treatment of Lung Cancer “Naturally”, Dr Bharat B. Aggarwal, PhD (February 23, 2012)
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