IV Curcumin – Avoiding Poor Oral Curcumin Absorption

Curcumin is the principal curcuminoid of turmeric root.  Curcuminoids are natural phenols responsible for the yellow color of turmeric.  For centuries, turmeric root has been used successfully for a wide range of medicinal purposes, but studies have revealed the poor absorption and low bio-availability of curcumin through the intestines.  Oral curcumin is used successfully to modulate inflammation and support health and longevity, but its poor absorption has limited its ‘mega-dose’ orthomolecular usage up to now.  As of June 2015, there were 116 clinical trials evaluating the possible anti-disease effect of curcumin in humans, including studies on cancer, gastrointestinal diseases, cognitive disorders, and psychiatric conditions.  This began the impetus and interest of IV curcumin.

IV or intravenous curcumin is a novel and promising adjunct to the care of the cancer and chronically ill patient population.  Studies have shown that oral administration of curcumin provides some benefit, but
absorption and distribution kinetics do not always allow maximal benefit.  As we stay up to date with BIORC protocols and treatment modalities, we have been happy to hear of early successes with IV curcumin with difficult to treat conditions.  At Purety Clinic, our holistic cancer treatment center of Santa Barbara is very thankful for the work of Dr Paul Anderson of AMSA in Seattle and his continued research and compilation for successful holistic cancer treatments.

At this point, IV curcumin is still experimental with potential extraordinary effects for patients in need.  Safe protocols have been set in place in order to avoid side effects and control proper usage.

From the Abstract (Anand. Curcumin and cancer: an “old-age” disease with an “age-old” solution.): Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called ‘‘curry powder”) that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival(PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR 4) and inflammation (NF-jB, TNF, IL-6, IL- 1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an ‘‘old-age” disease such as cancer requires an ‘‘age-old”
treatment. From the Abstract (Reuter, Gupta. Epigenetic changes induced by curcumin and other natural compounds.):

Epigenetic regulation, which includes changes in DNA methylation, histone modifications, and alteration in microRNA (miRNA) expression without any change in the DNA sequence, constitutes an important
mechanism by which dietary components can selectively activate or inactivate gene expression.

Curcumin (diferuloylmethane), a component of the golden spice Curcuma longa, commonly known as turmeric, has recently been determined to induce epigenetic changes. This review summarizes current knowledge about the effect of curcumin on the regulation of histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and miRNAs. How these changes lead to modulation of gene expression is also discussed. We also discuss other nutraceuticals which exhibit similar properties. The development of curcumin for clinical use as a regulator of epigenetic changes, however, needs further investigation to determine novel and effective chemopreventive strategies, either alone or in combination with other anticancer agents, for improving cancer treatment.

From Anand:
Two in vivo studies were reported showing the antitumor activity as well as chemosensitization effect of curcumin against pancreatic cancer. In a xenograft model study, pancreatic cancer cells were injected subcutaneously on the side of the abdomen of female nude mice.  Once tumor masses became established, animals were randomized to receive intravenous liposomal IV curcumin (40 mg/kg, 3 time per week) for 20 days. Treatment with liposomal curcumin resulted in reduced tumor size and visible blanching of tumors showing decreased expression of CD31 as well as VEGF and IL-8. These results indicate that curcumin suppressed pancreatic carcinoma growth in murine xenograft models and inhibited tumor angiogenesis.

Abstract of Chen.  An in vitro study of liposomal curcumin: stability, toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B-cells.:
Curcumin is a multi-functional and pharmacologically safe natural agent. Used as a food additive for centuries, it also has anti-inflammatory, anti-virus and anti-tumor properties. We previously found that it is a potent inhibitor of cyclosporin A (CsA)-resistant T-cell co-stimulation pathway. It inhibits mitogen-stimulated lymphocyte proliferation, NFkB activation and IL-2 signaling. In spite of its safety and efficacy, the in-vivo bioavailability of curcumin is poor, and this may be a major obstacle to its utility as a therapeutic agent. Liposomes are known to be excellent carriers for drug delivery…  We conclude that liposomal curcumin may be useful for intravenous administration to improve the bioavailability and efficacy, facilitating in-vivo studies that could ultimately lead to clinical application of curcumin.

Wilken. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma.Intravenous liposomal IV curcumin has been studied by our laboratory in mouse xenograft tumors of the oral cancer cell lines CAL27 and UM-SCC-1, and was found to be both nontoxic as well as effective at suppressing tumor growth. Xenograft mouse tumors were stratified into groups receiving no treatment, treatment with empty liposomes or treatment with liposome encapsulated curcumin and a statistically significant growth suppressive effect was observed in the liposomal curcumin group [Wang D, Veena MS, Stevenson K, Tang C, Ho B, Suh JD, Duarte VM, Faull KF, Mehta K, Srivatsan ES, Wang MB:
Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibition of nuclear factor kappaB by an AKT-independent pathway.

Clin Cancer Res 2008, 14:6228-6236.].
Abstract of Kurzrock.  Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Journal of Clinical Oncology.2005 Background: Because a role for nuclear factor-kB (NF-kB) has been implicated in the pathogenesis of pancreatic cancer, this transcription factor is a potential target for treatment of this devastating disease. Curcumin (diferuloylmethane) is a phytochemical with potent NF-kB-inhibitory activity. It is pharmacologically safe, but its bioavailability is poor after oral administration.
Methods: We encapsulated curcumin in a liposomal delivery system that would allow intravenous administration. We studied the in vitro and in vivo effects of this compound on proliferation, apoptosis, signaling and angiogenesis using human pancreatic cancer cells. Conclusions: Liposomal curcumin downregulates the NF-kBmachinery, suppresses growth, and induces apoptosis of human pancreatic cells, in vitro. Antitumor and anti-angiogenesis effects are observed in vivo. Our experiments provide a biologic rationale for treatment of patients suffering from pancreatic cancer with this nontoxic phytochemical encapsulated in liposomes for systemic delivery.