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Curcumin (“Indian Gold”): The Benefits

Constantine Kaniklidis

  [curcumin-600x400] 

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  [image] 

[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  [image]  [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].


Bottom Line:

  • 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.

Phytosomal-based Curcumin

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].

Particulate-based Curcumin

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.

Hydrophilic Curcumin

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.

 

 

Selected References

Al-Karawi D, Al Mamoori DA, Tayyar Y. The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials. Phytother Res 2015 Nov 27.

Belcaro G, Hosoi M, Pellegrini L, et al. A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment. Phytother Res 2014; 28(3):444-50.

Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011; 4: 354–364.

Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol 2015 May; 29(5):642-51.

Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol 2006; 4: 1035–1038.

Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 2008;14:4491–9.

Esmaily H, Sahebkar A, Iranshahi M, et al. An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial. Chin J Integr Med 2015; 21(5):332-8.

Estabeyoglu T, Huebbe P, Ernst IMA, Chin D, Wagner AE, Rimbach G. Curcumin-From molecule to biological function. Angew Rev Int Ed 2012; 51: 5308-5332.

Faria A, Pestana D, Teixeira D, Azevedo J, De Freitas V, Mateus N, Calhau C. Flavonoid transport across RBE4 cells: a blood-brain barrier model. Cell Mol Biol Lett 2010; 15: 234-241.

Goozee KG, Shah TM, Sohrabi HR, et al. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease. Br J Nutr 2015 Dec 14; :1-17.

He Y, Yue Y, Zheng X, Zhang K, Chen S, Du Z. Curcumin, inflammation, and chronic diseases: how are they linked? Molecules 2015; 20(5):9183-213.

Irving GR, Iwuji CO, Morgan B, et al. Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial. Trials 2015; 16:110.

Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J 2014; 13:11.

Jiang J, Wang W, Sun YJ, Hu M, Li F, Zhu DY. Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage. Eur J Pharmacol 2007; 561: 54-62.

Kaniklidis C. Why does curcumin contain anticancer properties? ResearchGate 2013 Dec 28.

Kaniklidis C. Edge-CAM Regimen V. 4.0. Breast Cancer Watch Digest. Special Issue. July 2014.

Kaniklidis C. CNS Metastasis from Breast Cancer – New Promise: A Review [2015 revision; pending publication]. Available on ResearchGate.

Panahi Y, Khalili N, Hosseini MS, et al. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med 2014; 22(5):851-7. [a]

Panahi Y, Saadat A, Beiraghdar F, Sahebkar A. Adjuvant Therapy with Bioavailability-Boosted Curcuminoids Suppresses Systemic Inflammation and Improves Quality of Life in Patients with Solid Tumors: A Randomized Double-Blind Placebo-Controlled Trial. Phytother Res 2014 Mar 19. [b]

Perrone D, Ardito F, Giannatempo G, et al. Biological and therapeutic activities, and anticancer properties of curcumin. Exp Ther Med 2015; 10(5):1615-1623.

Pluta R1, Bogucka-Kocka A, Ułamek-Kozioł M, et al. Neurogenesis and neuroprotection in postischemic brain neurodegeneration with Alzheimer phenotype: is there a role for curcumin? Folia Neuropathol. 2015;53(2):89-99.

Rahmani AH, Al Zohairy MA, Aly SM, Khan MA. Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways. Biomed Res Int 2014; 2014:761608.

Ryan JL, Heckler CE, Ling M, et al. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res 2013; 180(1):34-43.

Sanmukhani J, Satodia V, Trivedi J, et al.. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res 2014; 28(4):579-85.

Shanmugam MK, Rane G, Kanchi MM, et al. The multifaceted role of curcumin in cancer prevention and treatment. Molecules 2015; 20(2):2728-69.

Soldà C, Bardini R, Sperti C, et al. Phase II study of Gemcitabine and Curcumin (Meriva®) as first line treatment for locally advanced or metastatic pancreatic cancer: preliminary results. Ann Oncol (2015) 26 (suppl 6): vi.

Wang YF, Gu YT, Qin GH, Zhong L, Meng YN. Curcumin ameliorates the permeability of the blood-brain barrier during hypoxia by upregulating heme oxygenase-1 expression in brain microvascular endothelial cells. J Mol Neurosci 2013; 51(2):344-51.

Watson E. Sabinsa weighs into curcumin bioavailability debate. NutraIngredients 02 May 2011. At: http://www.nutraingredients-usa.com/Research/Sabinsa-weighs-into-curcumin-bioavailability-debate.

Yang YS, Su YF, Yang HW, Lee YH, Chou JI, Ueng KC. Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial. Phytother Res 2014; 28(12):1770-7.

Yu JJ, Pei LB, Zhang Y, Wen Zy, Yang JL. Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. J Clin Psychopharmacol 2015; 35(4):406-10.

Calico

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Hi Constantine,

Thank you for the update, I really appreciate all the information and research.
It was you that directed my attention to curcumin back when I was diagnosed and you also pointed out the minimal ingredient of the supplement I used back then, so I could make an informed decision and switch.
Glad to see it is so widely known (my onc should know as well I hope, he did look at me back then like I have two heads but was receptive when I mentioned the doc at head of research. I wasn't taking it regularly in the last 6 months but will def start asap. Much appreciation for what you do to help the cancer community, Dear Edgy [smile] 

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Calico:

Thanks for the acknowledgment.

Based on successes in oncology and inflammatory diseases, the research scene in curcumin has exploded open - there are now over 124 NCI-registered clinical trials alone, with several dozen more under private registry or institutional sponsorship, and I anticipate further positive findings across a  wide spectrum of diseases, and with no significant safety signals raised (as per my Drug Interactions in Oncology review, curcumin now having been tested concurrently with a large segment of our major oncotherapy agents without clinically significant adverse interactions), it will be  recognized along with Vitamin D3 as an essential disease-preventive nutrient, even independent of its impressive therapeutic applications. 

kind regards
Constantine
Calico

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Wow! 124 trials! 
Thank you for the update [wink] 

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Constantine,
What are your current recommendations regarding daily intake of Curcumin at this time? Any change from the previous Edge Cam? 

My daughter is going back on the daily regimen since you posted this very helpful update, which she read and is thankful for as well. Looking forward to your recommendation [smile]

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Still taking it, still thankful dear Edgy [wink]
It is quiet here but nonetheless, still reading and appreciative of all your research that you did for us!

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Dear Calico;

Apologies for the delay in responding but as always so nice hearing from you, a young "old" [smile] friend. Hope you're well and that your daughter Gina - what a nice serendipity! - is doing well too. 

There is an update to my regimen, now up to Edge-CAM V. 5.0 as of July 1st of this year, which represents an extensive revision and update of the curcumin recommendations, along with new information on Vitamin D3 and melatonin. I haven't posted it here as yet - there are some gymnastics involved because the length of a posting is restricted, and my Edge-CAM page would have to somehow to broken into multiple parts rather clumsily - but as a compromise I have posted to a "private" site, at:

http://edgecam.evidencewatch.com/

which is not indexed and to which I do not provide the link except to the NS community (and it is marked at the top of page as "Commissioned on behalf of No Surrender Breast Cancer Foundation (NSBCF)" which several other pages I am launching (including an update  on TNBC) will also display).

As to my current guidance on curcumin, it has indeed changed significantly: I now counsel:

(1)  For prevention (namely in women without any active malignancy, past or present), use of the phytosomal formulation of curcumin, commercially known as Meriva, dosed at 1000 mg daily (two capsules, available most affordably from PipingRock.com.

(2)  For prevention in non-active disease but high-risk women, I counsel 1500 - 2000 mg daily of phytosomal curcumin, the higher amount in the highest risk cases (BRCA, family history, or other risk-elevating factors).

(3)  For treatment of active  malignancy or to reduce risk of recurrence, I counsel a combination of 2000 mg of Meriva PLUS 3000 mg of a Sabinsa-certified piperine-bioavailability enhanced formulation, leveraging the unique benefits of each type, based on the best evidence to date which I present on that site.

As we learn more about curcumin formulations, I make the needed adjustments to preserve optimality of efficacy and safety.

Any questions on this - or on anything else - please don't hesitate to ask.

Best of fortune to you and yours,

Warmest regards

Constantine   

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This is wonderfully informative. Thank you, Constantine!
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Calico

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Hi Constantine,
It's so nice to hear from you, I missed reading your posts. I hope that you and your family are well and enjoying the nice long summer days. I have taken to the trails again after a long hiatus and I enjoy being outdoors more than ever.
Thank you for asking about 'my' Gina [wink] She is doing much better (and appreciates you asking about her). It appears there is a 5 year 'rule' to chemo brain that applies to other drugs too. Her memory function is better, yet improvement is still needed but better overall, much improved. Working part time and she tackled her most fearful class, Calc II over summer, something she used to not be afraid of before since she was a nerd all her life (pre drug side effects).....but there is hope.

I appreciate your research regarding the Edge Cam and keeping us informed. Thank you very much for sharing your site [smile], so very informative and explained in detail.  I will definitely add the Meriva Curcumin in combination with the C3 complex [smile] 





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Hi Constantine,
Still following the CAM, especially the Curcumin.
I tried the Meriva (tried the Curcumin Phytosome with Meriva by Doctor's Best, tolerated it well but I think it might thin my blood, which isn't necessarily a bad thing, just need to figure a dose to alternate the other Curcumin(I use the NOW brand, Swanson Vitamins has a 20% deal often).
Just wanted to let you know that your research shared with us is still very much appreciated and followed.

xoxo

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Dear Calico:

 

Yes, any curcumin preparation can have a modest effect on coagulation although it is still unclear whether this is at a clinically significant level, especially in the absence of other anticoagulating agent (like aspirin, NSAIDs or warfarin).

 

However, I counsel that a Vitamin K Complex formulation can be taken to modulate this potential effect (I recommend Vitacost's Ultra Vitamin K with Advanced K2 Complex), often independently desirable given that only about one-third (35%) of  the population have total usual intakes meeting or exceeding greater proscribed adequate intake levels of Vitamin K, as I showed in my paper "Multivitamin Mineral Supplementation – Enough Is Not Enough: Review of Micronutrient Deficiencies" (available on Academia.edu), and remember also that prospective cohort analysis of PREDIMED Study data found that an increase in dietary intake of vitamin K is associated with a reduced risk of cardiovascular, cancer, and all-cause mortality.

 

As to dosing, Meriva is optimized at 2000 mg daily for advanced/metastatic disease, 1000 mg in the non-metastatic context, and 500 mg in at-risk non-cancer populations.  

 

Thanks much, Calico, both for your always kind appreciation, and for your contributions to the No Surrender Breast Cancer Community!

 

Kind regards

Constantine

Calico

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Dear Constantine,

You are always so kind to find a solution, thank you for that. I am going to look into Vit K, however, I seem to have a theory stuck in my head that a 'fluid' thinned blood flow may prevent cancer cells from getting too comfortable on cell walls and are washed away..so somewhat of a thinning of blood may perhaps be beneficial?  Ok....it was more professionally written from what I remember [biggrin] or perhaps it never existed, so would somewhat of a thinning of blood benefit breast cancer survivors?  


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Dear Calico:

 

Smart question!  There's been a lot of media attention to this theme - of either anticoagulants (like warfarin (Coumadin)) or antiplatelets (like aspirin) being associated with lower cancer risk - based on a large observational study in Norway [Haaland GS, Falk RS, Straume O, Lorens JB. Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years. JAMA Intern Med. 2017 Dec 01; 177(12):1774-1780.] published in JAMA Internal Medicine this past December (2017).

 

However, tantalizing though this is, the study actually failed to convincingly support this conclusion:

 

  1. As the study's lead investigator cautioned: "The findings don't prove that warfarin reduces the risk of cancer", and Ken Lichtenfeld of the ACS adds the highly sensible warning that: "The study does not suggest that we should be prescribing warfarin to reduce cancer risk. No one should be taking warfarin as a cancer prevention measure."
  2. In addition, the study did NOT collect critical data on other medications or risk factors, confounding the study's conclusions.  So, for example, many (most in fact) of the subjects were taking warfarin for cardiac arrhythmia disorders (atrial fibrillation and atrial flutter), but in that case, most would have also been on a beta blocker, a standard of care in atrial rhythm disorders and one that, independently has been associated with lower cancer risk, so the observed benefit may have been consequent to the beta blockers, not warfarin itself.  And many would have been on statins, also with an association with reduced cancer risk. (And many other potential confounders were not controlled for, along with other methodological limitations). Thus, the study was insufficiently powered to detect any of these confounding possibilities.
  3. The study authors speculate rather over-boldly on the putative causative mechanism of benefit being inhibition by warfarin of the AXL receptor on tumor cells, a known property of this anticoagulant.  However, the study's lead investigator, Dr. James Lorens at the University of Bergen (Norway) has ownership interest in the BerGenBio ASA company, a commercial firm actively marketing and promoting AXL inhibitors.  This conflict of interest erodes confidence in the independence of the research team, given the well-known association of dramatically more favorable results being reported in studies with conflictive allegiance.

 

Similar problems infect the research on antiplatelets (with likely the exception of low-dose/baby aspirin), and given the potential of chronic administration of antiplatelet and anticoagulant agents to induce some degree of thrombocytopenia (compromised platelet counts) while potentially elevating risk of bleeding complications, along with some isolated reports of increased cancer incidence, the speculative data cannot prudently as yet inform clinical practice.

 

Finally anticoagulation and antiplatelet function are different from CELL ADHESION, the property of tumor cells that is an essential component of what's called the metastatic cascade, but that is a fundamentally different phenomenon (one of the activities that underlies curcumin's anti-metastatic properties is in fact to regulate positively tumor cell adhesion - and tumor migration and cell proliferation and angiogenesis, all also components of the metastatic cascade - so we already have a powerful cell-adhesion blocker in this natural agent).

 

If robust prospective randomized data should at some point appear to change my conclusions here, I'll post the information here.

 

Thanks for raising this important issue!

 

Best fortune

Constantine

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Thank you! 


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Reply with quote  #15 
I am digesting in small bites [biggrin]
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