Curcumin (“Indian Gold”): The Benefits
Curcumin is the bright yellow color pigment extracted from the spice turmeric (often known as "Indian Gold"). It is an extraordinary natural agents across dozens of human diseases, and as many readers who follow my research know, it forms a critical part of my well-known Edge-CAM anti-cancer regimen (developed for the No Surrender Breast Cancer Foundation (NSBCF)), of which it forms a sub-part known as "MEDiC" along with Melatonin plus EGCG (from Green Tea Extract) plus Vitamin D3 plus Curcumin, which stand together evidenced as one of the most powerful regimens in the battle against multiple types of human cancer.
Curcumin: The Magic
[Source: http://www.curcuminresearch.org. Bharat B. Aggarwal. MD Anderson Cancer Center]
The multifaceted role of this dietary agent is mediated through its inhibition of dozens of critical molecular pathways at multiple levels [Shanmugam 2015]. Besides its anticancer preventive and therapeutic activity [Perrone 2015] [Rahmani 2014] [Kaniklidis 2013], the evidence finds for:
- anticancer preventive and therapeutic activity
- anti-inflammatory / anti-arthritic;
- anti-infective; cardioprotective;
- lipid-modulating [Panahi 2014 a];
- thrombosuppressive (anti-clot);
- hepatoprotective (against liver toxicity);
- anti-ulcerative-colitis; antidiabetic, anti-obesity, and anti-metabolic syndrome [Yang 2014] [He 2015];
- powerful antidepressant (the BCM-95 formulation of curcumin matching the conventional antidepressant fluoxetine (Prozac) in a randomized controlled trial [Sanmukhani 2014],and can enhance their efficacy [Yu 2015], with antidepressant benefits confirmed in meta-analysis [Al-Karawi 2015);
- anti-anxiety [Esmaily 2015];
- anti-lichen and anti-mucositic;
- and pro-cognitive functioning activity (including potential modulation of the pathology of Alzheimer's Disease via neuroprotective and cognitive-enhancing properties [Goozee 2015]),
among dozens of other benefits in dermatological, cardiovascular, neurological, skeletal-muscular, and endocrinological human systems, and note that these benefits are supported by human clinical evidence (selectively cited below), not just preclinical (in vitro and in vivo) data.
There are now over 300 pages of publication references for curcumin in the medical literature as confirmed by the vast online Curcumin Resource Database (http://crdb.in/), totaling over 9000 studies stretching almost a century, from 1919 to 2015.
Curcumin: The Anticancer Advantage [Source: http://www.curcuminresearch.org. Bharat B. Aggarwal. MD Anderson Cancer Center]
In the oncology-specific context, a curcuminoid (480 mg) and quercetin (20 mg) combination therapy (curcuminoids are the active anticancer component of curcumin) consumed over a 6 month period was found to reduce both the size and number of colorectal polyps in patients with familial adenomatous polyposis [Cruz-Correa 2006]. And cross-confirmative of these findings, a month of curcuminoid supplementation reduced the number of foci in smokers with aberrant crypt foci on colonoscopy, in a non-randomized open-label study, where 4 grams/daily but not 2 grams/daily was effective [Carroll 2011].
And in one of our most challenging malignancies, high-dose curcumin at 8 g/d induced response in several patients with advanced pancreatic cancers [Dhillon 2008]. In confirmation, a recent Phase II trial found that the addition of curcumin (as Meriva, 2000 mg/daily) to gemcitabine (Gemzar) for the treatment of locally advanced or metastatic pancreatic cancer conferred a high (60%) disease control rate [Soldà 2015].
Furthermore, findings from a recent randomized double-blind placebo-controlled trial [Panahi 2014 b] of curcuminoids in patients with solid tumors (including breast cancer) supported the clinical efficacy of adjuvant therapy with curcuminoids using a bioavailable phosphatidylcholine complex formulation) in improving the QoL of patients with solid tumors. This finding was accompanied by a significant reduction in serum levels of key adverse inflammatory mediators and biomarkers (IL-6, TNF-α, MCP-1, CGRP, substance P and hs-CRP) revealing that curcuminoids suppress systemic inflammation. Thus adjuvant therapy with a bioavailable curcuminoid preparation can significantly improve both QoL and suppress systemic inflammation in patients with solid tumors under treatment with standard chemotherapy. In addition, a randomized, double-blind, placebo-controlled clinical trial [Ryan 2013] found that oral curcumin dosed at 6 grams daily during radiotherapy in breast cancer patients significantly reduced the severity of radiation dermatitis. And in further confirmation, a recent controlled study [Belcaro 2014] reported significant improvement in QoL and the reduction in side effects associated with chemotherapy or radiotherapy in 160 cancer patients (including breast cancer) treated for 4 months with a proprietary curcumin-phosphatidylcholine phytosome complex (commercially available as Meriva).
Collectively, these and numerous other lines of evidence strongly entail the exceptional benefits of curcumin against a wide spectrum of human diseases, including numerous challenging malignancies, delivering these benefits with uncommon tolerability and safety (for further information, and recommendations on dosing and commercial formulations, see my Edge-CAM regimen [Kaniklidis 2014].
- The Wrong Question:
- Why should anyone take curcumin?
- The Correct Question:
- Why should anyone not take curcumin?
A Consumer's Guide to Curcumin
Sabinsa-standardized C3 Complex
This is a standardized formulation delivering optimal amounts of the critical active component of curcumin, known as curcuminoids, where a pepper-derived compound piperine is used to enhance bioavailability. It is the most widely studied form, for which we have the greatest base of peer-reviewed studies, and the one most widely used in oncology trials, including the in-progress CUFOX trial which is combining curcumin with the standard-of-care FOLFOX (5-FU, folinic acid and oxaliplatin) chemotherapy regimen in patients with inoperable colorectal cancer [Irving 2015], with preliminary findings of enhanced efficacy in the context of colorectal liver metastasis, exerting anti-proliferative and proapoptotic (programmed death) effects on patient-derived cancer stem cells. It has also been used in completed successful randomized controlled trials in favorable cardiovascular lipid/cholesterol modulation [Panahi 2014 (a)], in an MD Anderson Phase IIb prevention study in women at increased risk for breast cancer, in depression and schizophrenia, osteoarthritis, in dyslipidemia and obesity, in oral lichen planus, and in, to date, over 34 clinical trials and dozens of other studies.
Thus, in the cancer context, no other formulation of curcumin is more evidenced by the clinical data to date, and this form remains the first choice in oncology deployment. There are currently 12 commercial preparations identified by Sabinsa Corporation as using their C3 Complex formulation (http://www.curcuminoids.com/users.htm), although the list may not be exhaustive; of these, Doctor's Best, Physician Naturals, and Pure Prescriptions are some of the more commonly available commercial labels.
Tip: the absorption of any Sabinsa-standardized C3 Complex preparation can be enhanced when taken with a fatty (oily) meal (such as with olive oil).
Essential Oils-based Curcumin
A second formulation is BCM-95 (manufactured by Arjurna Natural Extracts), which combines curcuminoids with other components of turmeric such as essential turmeric oils that have their own anticancer activity. Life Extension Bio Curcumin is one BCM-95-based commercial product. This form of curcumin was shown to have especially powerful antidepressant activity, along with benefits in inflammatory conditions and bone/joint diseases.
A third formulation is known as a phytosomal form, meaning it achieves enhanced bioavailability by binding curcumin to phosphatidycholine (PC), in humans a source of choline which also functions as a precursor to the neurotransmitter, acetylcholine. Several studies have demonstrated the anticancer benefit of phytosomal-based curcumin, along with anti-inflammatory and anti-osteo arthritic activity, and benefits in prostate/urinary disease, among other applications. Phytosomal-based curcumin (also known as Curcumin Phytosome) is marketed under the Meriva (manufacturer, Indena). Although widespread market has suggested that Meriva is vastly more bioavailable than piperine-enhanced Sabinsa-standardized C3 Complex, this has been disputed - convincingly we believe - by Sabinsa founder and curcumin expert Dr Muhammed Majeed, who has noted that phytosomal-based curcumins like Meriva only increase the bioavailability of curcuminoid metabolites, but not of the crritical active ingredients, curcuminoids, themselves [Watson 2011].
The fourth formulation, under the commercial label Longvida (verdure Sciences) uses what's called solid lipid curcumin particle technology (SLCP) based on a form of free curcumin that designed to survive the stomach environment to assure better absorption, bio-availability and efficacy, and the particulate technology involved allows the company to claim that this is the only form of curcumin that can cross the blood brain barrier (BBB). Although our own research suggests that the claim of being the only Curcumin formulation to have cross-BBB capability is arguable and requires more robust clinical trials, nonetheless it is the only form to date to demonstrate significant improvements in short-term memory after consumption [Cox 2015], but this was a small clinical trial in healthy older adults and the benefit was for up to 3 hours after consumption, leaving it unclear what more durable impact it may have. Still, these findings are sufficiently suggestive to warrant favoring the Longvida formulation if one's primary intent is benefit against age-related short-term memory loss.
A fifth formulation, under the commercial CurcuWin (OmniActive Health Technologies) label, combines curcumin with a hydrophilic carrier to make it more dispersible in water, which is claimed to yield the most dramatic effect on bioavailability, however the study [Jäger 2014] was sponsored by the manufacturer, and used a relatively short sampling time frame rather than a more realistic 24 sample, so independently, we need robust human clinical studies of actual benefit before judging that such bioavailability is of any true clinical relevance.
[Technical Note - The Issue of Brain Activity: Myth and Reality]
It is often claimed that at least some forms of curcumin can cross the protective blood-brain barrier (BBB) to allow them to exert CNS (central nervous system) effects in the brain which is otherwise relatively impermeable, which most of the focus being on the Longvida formulation because of some human clinical evidence of benefit in memory function [Cox 2015], besides weaker and only provisional preclinical data. But several studies have in fact shown that native curcumin, due to its lipophilicity, can cross the blood-brain barrier, reaching brain tissue at a functional pharmacological level [Estabeyoglu 2012, [Faria 2010], [Pluta 2015].
But a more serious error in reasoning also occurs. From this cross-BBB activity, many have deduced the potential use and benefit in the treatment of brain metastasis from various cancers, including breast cancer, and also in the treatment of brain tumors like glioblastoma (GBM). However this is in error and is based on a misunderstanding of what is required for anticancer activity in the brain: it is not enough that an agent cross the BBB; favorable activity is also dependent on other complex factors of dynamic flow (and flow gradient differentials) and resistance, as well as factors affecting barrier permeability. In fact, some of the non-oncological CNS benefits of curcumin may modulate permeability negatively [Kaniklidis 2015]. Thus, in a study of curcumin's effect on the permeability of the blood–brain barrier during brain ischemia / hypoxia [Wang 2013], it was found that curcumin improved the barrier function of the BBB under these ischemic conditions, which is good for protection against ischemic damage (stroke) but definitely not good for antimetastatic brain activity, as enhanced barrier function restores greater impermeability, limiting cranial anticancer activity. This is further confirmed in other studies that document curcumin's reversal of the permeability of the blood-brain barrier, hence protecting blood–brain barrier integrity [Estabeyoglu 2012] [Jiang 2007], which again would limit curcumin-based anticancer activity in the brain.
The clinical lesson to take away here is that from any curcumin formulation's ability to merely cross the blood-brain barrier (BBB), it does not even in the remotest degree follow that curcumin will exert clinical significant anticancer activity within the brain, and in fact we have no data whatever of cranial anticancer / antimetastatic benefit. This does NOT mean that curcumin is of no potential benefit in the brain-metastatic context, since it must be remembered (1) that mortality is generally due to extracranial metastases (lung, liver), not cranial mets themselves, and (2) in the case of brain metastases, the blood-brain barrier (BBB) is often partially disrupted [Kaniklidis 2015]. Still, the possibility of restoration of the integrity of the barrier function strongly suggests that on its own, curcumin is unlikely to provide significant and clinical relevant anticancer activity in the brain, although it's anticancer activity in other organs and viscera (see my discussion above) may still hold some potential attraction in fighting systemic disease.
Patient Buying Summary
1. The preponderance of data supporting curcumin's benefits across multiple diseases and conditions still rests with the piperine-enhanced Sabinsa-standardized C3 Complex formulations, discussed and identified above.
2. For potential benefit in short-term memory function in healthy older adults, there is limited but suggestive evidence that particulate-based curcumin (Longvida) may hold some special advantage although this still requires confirmation in larger more robust trials.
3. For the specific oncology context, for general broad anticancer activity, no formulation has shown superiority over piperine-enhanced Sabinsa-standardized C3 Complex formulations, and that remains the best-evidenced option to date.
4. Data shows that curcumin is relatively well-tolerated even at higher doses of six grams daily, but tolerability always shows some non-trivial individual variation, so a user who experiences any GI adverse events on Sabinsa-standardized C3 Complex formulations can do a trial of a phytosomal-based curcumin like Meriva which appears to have minimal side effects.
5. We will review any new data that may change these clinical lessons as they may appear in the future.
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