Presentation on theme: "Modified Citrus Pectin & Galectin-3 The Role of Modified Citrus Pectin and Galectin-3 in the Prevention and Treatment of Metastatic Cancer."— Presentation transcript:
Modified Citrus Pectin & Galectin-3 The Role of Modified Citrus Pectin and Galectin-3 in the Prevention and Treatment of Metastatic Cancer
Elevated Galectin-3 in the body is directly involved in: – Cancer – Cardiovascular Disease – Chronic Hepatitis – Kidney Disease – Diabetes – Inflammation & Fibrosis – Others Galectin-3 & Disease
Overall Average 11.9 Galectin-3 Levels & Mortality from All Causes in the General Population: PREVEND
In Cancer, Galectin-3 plays a role in: – Cell to Cell Adhesion – Aggregation of Cancer Cells – Tumor Growth – Metastasis – Angiogenesis – Inhibition of Apoptosis Galectin-3 & Cancer
MCP is derived from the pith of citrus fruit peels Complex polysaccharide fiber of repeating galacturonic acid groups with neutral sugar side chains Unmodified citrus pectin molecular weight 50 to 300 kiloDaltons (kDa) with esterification ~70% Optimal biological activity: molecular weight <13 kDa with esterification <10%, and specific structure What is Modified Citrus Pectin (MCP) ?
Binds to Galectin-3 molecules Blocks aggregation of cancer cells Blocks docking of cancer cells Blocks interactions with endothelium necessary for angiogenesis Modified Citrus Pectin is a Galectin-3 Blocker
Modified Citrus Pectin Cancer Research
Anti-Cancer and Anti-Metastasis Blocking of Galectin-3 Effects Synergistic Effect with Chemotherapy Protection Against Post-Radiation Damage Improved Quality of Life Benefits of MCP in Cancer Treatment
Method: MCP’s inhibition of prostate cell adhesion to endothelial cells. 0.1% and 1.0% MCP in rats’ drinking water; controls had plain water Results: Significant reduction in lung metastases -- 50% reduction in 0.1% group; 56% reduction in 1.0% group (P<0.03 & P<0.001). Inhibition of Spontaneous Metastasis in a Rat Prostate Model by Oral Administration of Modified Citrus Pectin Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle, TS, Lehr J, Donat TL, Tait L, Hogan V, Raz A Wayne State University School of Medicine, Detroit, MI, USA J Natl Cancer Inst 1995 87(5):348-53.
Conclusion: MCP acted as potent inhibitor of spontaneous prostate carcinoma metastasis. Inhibition of Spontaneous Metastasis in a Rat Prostate Model by Oral Administration of Modified Citrus Pectin Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle, TS, Lehr J, Donat TL, Tait L, Hogan V, Raz A Wayne State University School of Medicine, Detroit, MI, USA J Natl Cancer Inst 1995 87(5):348-53.
Method: MCP’s inhibition of breast & colon cancer progression; MCP’s interaction with Galectin-3 Results: 70.2% Reduction in Breast Tumor Growth – Breast Angiogenesis: 66% Reduction – Breast to Lung Metastasis: 0% MCP v. 100% Control – Colon to Liver Metastasis: 0% MCP v. 60% Control – Colon to Lymph Metastasis: 25% MCP v. 100% Control Inhibition of Human Cancer Cell Growth & Metastasis in Nude Mice by Oral Intake of Modified Citrus Pectin Nangia-Makker P, Hogan V, Honjo Y, Baccarini S, Tait L, Bresalier R, Raz A Wayne State University, School of Medicine, Detroit, MI, USA J Natl Cancer Inst. 2002 94(24):1854-62.
Conclusion: MCP inhibits carbohydrate mediated tumor growth, angiogenesis & metastasis via effects on Galectin-3 function Inhibition of Human Cancer Cell Growth & Metastasis in Nude Mice by Oral Intake of Modified Citrus Pectin Nangia-Makker P, Hogan V, Honjo Y, Baccarini S, Tait L, Bresalier R, Raz A Wayne State University, School of Medicine, Detroit, MI, USA J Natl Cancer Inst. 2002 94(24): 1854-62.
Method: Human vascular endothelial cell layer & PC-3 prostate cancer cells. Results: Strong tumor cell death response with MCP, compared to controls. Modified Citrus Pectin Induces Cytotoxicity of Prostate Cancer Cells in Co-Culture with Human Endothelial Monolayers Weiss T, McCulloch M, Eliaz I Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA EcoNugenics, Santa Rosa, CA, USA Intl Conference on Diet & The Prevention of Cancer 1999, Tampere, Finland.
Method: MCP 15 g/day to patients with biochemical relapse post local therapy. PSA Doubling Time (PSADT) evaluated at intervals. Results: MCP significantly increased PSADT in prostate cancer patients. Strum S, Scholz M, McDermed J, McCulloch M, Eliaz, I Prostate Oncology Specialist, Marina del Rey, CA, USA Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA EcoNugenics, Santa Rosa, CA, USA. International Conference on Diet & The Prevention of Cancer 1999, Tampere, Finland. Effect of Modified Citrus Pectin on PSA Doubling Time in Prostate Cancer Patients: A Pilot Clinical Trial
Patient MCP Use (Months) PSADT ChangeStatus Patient 1 5193% Response Patient 2 6193% Response Patient 3 380% Response Patient 4>1555% Response Patient 5 66% P. Response Patient 6 6-7% Stable Disease Patient 7 5-69% No Response Pilot Clinical Results: MCP’s Effect on PSA Doubling Time
Method: 10 men with biochemical prostate cancer relapse used MCP: 15g daily for 1 year. Modified Citrus Pectin Increases the Prostate-Specific Antigen Doubling Time in Men with Prostate Cancer: A Phase II Pilot Study Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI Healing Touch Oncology, Marina del Rey, CA, USA Prostate Cancer & Prostatic Disease 2003;6(4):301-4.
Results: MCP significantly increased PSADT in 7 out of the 10 participants (p<0.01). Modified Citrus Pectin Increases the Prostate-Specific Antigen Doubling Time in Men with Prostate Cancer: A Phase II Pilot Study Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI Healing Touch Oncology, Marina del Rey, CA, USA Prostate Cancer & Prostatic Disease 2003;6(4):301-4.
968 % * * Phase II Study: PSADT Results After 1 Year
Using Splines to Detect Changes in PSA Doubling Times Guess B, Jennrich R, Johnson H, Redheffer R, Scholz M, Healing Touch Oncology, Marin del Ray, CA, Department of Statistics, UCLA, CA, The Prostate 2003 54:88-95.
MCP Typical Patient Results
Method: MCP 15g daily. Results: 49 patients with advanced solid tumors. 29 evaluated after 2 months -- 21% showed stabilization & improvements in quality of life. – One patient w/ metastasized prostate carcinoma showed 50% decrease in PSA, with significant increase in quality of life & decrease in pain. Clinical Benefit in Patients with Advanced Solid Tumors Treated with Modified Citrus Pectin Azémar M, Hildenbrand B, Haering B, Heim ME, Unger C Albert-Ludwigs-University in Freiburg, Germany Sonnenberg-Klinik, Bad Sooden-Allendorf, Germany Clinical Medicine: Oncology 2007 1:73–80.
Conclusion: MCP shows clinical benefits & improvements in quality of life in advanced cancer patients. Clinical Benefit in Patients with Advanced Solid Tumors Treated with Modified Citrus Pectin Azémar M, Hildenbrand B, Haering B, Heim ME, Unger C Albert-Ludwigs-University in Freiburg, Germany Sonnenberg-Klinik, Bad Sooden-Allendorf, Germany Clinical Medicine: Oncology 2007 1:73–80.
Method: 5 groups of 15 mice. MCP: 0.0%, 1.0%, 2.5% and 5.0%; and negative control. – Colon cancer cells injected into spleen except negative control - - liver metastasis observed after 3 wks. ELISA used to detect Galectin-3. Results: MCP groups: Metastasis 80%, 73.3% & 60%. MCP 0.0%: Metastasis100%. Inhibitory Effect of Modified Citrus Pectin on Liver Metastasis in a Mouse Colon Cancer Model Liu HY, Huang ZL, Yang GH, Lu WQ, Yu NR Guangzhou Medical College, Guangzhou, China World J Gastroenterol 2008 14(48): 7386-7391.
Conclusion: MCP significantly reduced liver metastasis. Inhibitory Effect of Modified Citrus Pectin on Liver Metastasis in a Mouse Colon Cancer Model Liu HY, Huang ZL, Yang GH, Lu WQ, Yu NR Guangzhou Medical College, Guangzhou, China World J Gastroenterol 2008 14(48): 7386-7391.
Method: 1% MCP treatment of human prostate cancer cell lines (LNCaP & PC3) and mouse prostate cancer cell lines (CASP2-1 & CASP1-1) PectaSol-C Modified Citrus Pectin Induces Apoptosis & Inhibition of Proliferation in Human & Mouse Androgen Dependent & Independent Prostate Cancer Cells Yan J, Katz A Columbia University Medical Center, New York, NY, USA Integrative Cancer Therapies 2010 9:197-203.
Results: Confirmed apoptosis and inhibition of cancer cell proliferation 4 day MCP treatment showed cytotoxicity: – 52.28% in LNCaP – 48.16% in PC3 – 23.03% in CASP2-1 – 49.01% in CASP1-1 PectaSol-C Modified Citrus Pectin Induces Apoptosis & Inhibition of Proliferation in Human & Mouse Androgen Dependent & Independent Prostate Cancer Cells Yan J, Katz A Columbia University Medical Center, New York, NY, USA Integrative Cancer Therapies 2010 9:197-203.
Method: 48 hour effects of PectaSol on Doxorubicin (Dox) cytotoxicity, apoptosis and cell cycle in prostate cancer cell lines. Combination Effect of PectaSol and Doxorubicin on Viability, Cell Cycle Arrest and Apoptosis in DU-145 and LNCaP Prostate Cancer Cell Lines Najmeh T, Houri S, Parvin M, Firouzeh B, Arash HN, Abdolfattah S, Ebrahim H Tehran University, Tehran, Iran Cell Biology International (2012) doi:10.1042/CBI20110309. IC 50 Decrease: 1.5 foldIC 50 Decrease: 1.3 fold
Conclusion: Lower, less toxic doses Dox needed when combined with PectaSol. Combination Effect of PectaSol and Doxorubicin on Viability, Cell Cycle Arrest and Apoptosis in DU-145 and LNCaP Prostate Cancer Cell Lines Najmeh T, Houri S, Parvin M, Firouzeh B, Arash HN, Abdolfattah S, Ebrahim H Tehran University, Tehran, Iran Cell Biology International (2012) doi:10.1042/CBI20110309.
MCP can enhance therapeutic effect of chemotherapy drugs and treatment of chemo resistant cancers – Cisplatin (Platinol), Bortezomib (Velcade), Dexamethasone (Decadron), Doxorubicin MCP use very important in preventing post chemotherapy & radiation damage – Specifically post radiation induced inflammation and fibrosis MCP During Chemotherapy & Radiation
MCP Reduces: – Primary Tumor – Angiogenesis – Metastatic Process MCP Provides: – Blocking of Galectin-3 Effects – Synergistic Effect with Chemotherapy – Protection Against Post-Radiation Damage – Improved Quality of Life Summary: MCP in Cancer Treatment
Modified Citrus Pectin Immune Research
Modified Citrus Pectin: Induces NK Cell Activation Induces NK Cell Activity Activates T Cytotoxic Cells Increases B Cell Activation MCP Immune System Benefits
Method (Part I): Healthy human blood samples incubated with increasing doses of MCP and antibodies. At 24 hours samples lyzed and run on a flow cytometer. Analyzed % of activated T-cytotoxic cell, B-cells, and NK-cells; and % increase over untreated control. Activation of Human T-Cytotoxic Cell, B-Cell, and Natural Killer (NK)-Cells and Induction of NK-Cell Activity Against K562 Chronic Myeloid Leukemia Cells with Modified Citrus Pectin Ramachandran C, Wilk, B, Hotchkiss, A, Eliaz, I & Melnick SJ Dharma Biomedical, Miami, FL, USA, EcoNugenics, Santa Rosa, CA, USA Eastern Regional Research Center, ARS, USDA, Wyndmoor, PA, USA Department of Pathology, Miami Children's Hospital, Miami, FL, USA BMC Complementary and Alternative Medicine 2011, 11:59.
** ** *p < 0.05 ** p < 0.01 Results Part I: MCP Activates T-Cytotoxic Cells
** *** Results Part I: MCP Increases B-Cell Activation
** * * Results Part I: MCP Increases NK Cell Activation
Method (Part II): NK cell ability to induce leukemia cell death analyzed by co-incubating MCP-treated lymphocytes with K562 T-cell leukemia cells. Healthy human lymphocyte samples treated with increasing doses of MCP. After 24 hours, K562 labeled. Plates returned to incubator (for 4 hrs) to induce leukemia cell death. MCP: Induction of NK-Cell Activity Against K562 Chronic Myeloid Leukemia Cells
Results Part II: MCP Induces NK Cell Activity
Modified Citrus Pectin: Chelation & Detoxification Research
Forms stacked “egg box” structure Each pocket negatively charged Negative charge binds heavy metals Toxic metal trapped in the “egg box” Safely excreted from the body MCP Heavy Metal Elimination
Methods: MCP administered for 6 days. Baseline 24 hr urine collection before MCP, and on days 1 and 6. Days 1 - 5: MCP 15 g/day & Day 6: MCP 20 g/day. The Effect of Modified Citrus Pectin on Urinary Excretion of Toxic Elements Eliaz I, Hotchkiss AT, Fishman ML, Rode D; Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA; Eastern Regional Research Center, ARS, USDA, Wyndmoor, PA, USA; UC, Davis, CA, USA Phytother Res 2006 20(10):859-64.
Results: Urinary excretion of lead, mercury, cadmium & arsenic increased. Essential minerals not changed. No side effects reported. The Effect of Modified Citrus Pectin on Urinary Excretion of Toxic Elements Eliaz I, Hotchkiss AT, Fishman ML, Rode D; Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA; Eastern Regional Research Center, ARS, USDA, Wyndmoor, PA, USA; Univer. of CA, Davis, CA, USA Phytother Res 2006 20(10):859-64.
* # # * # # * *p <.05 #p <.10 The Effect of Modified Citrus Pectin on Urinary Excretion of Toxic Elements
MCP Chelation: Increased urinary excretion of toxic metals Demonstrated heavy metal chelation due to reduced molecular size & esterification 10% rhamnogalacturonan II -- known for binding affinity and immune enhancement Does not affect essential minerals No side effects reported MCP & Urinary Excretion of Toxins
Eliaz I. Amitabha Medical Clinic & Healing Center, Sebastopol, California, USA. EcoNugenics, Santa Rosa, California, USA. 228 th ACS National Meeting, Philadelphia, PA. 2004. Methods: Oral intake 5 g Modified Citrus Pectin/3x day for 4-10 months. Base line body burden and change measured with DMPS challenge (250mg i.v. followed by 6 hr. urine collection). Results: All subjects showed significant decrease in Mercury levels. Average decrease was 62.17%, ranging between 38.13% & 74.83% (p=0.0313). No significant side effects were noted. Modified Citrus Pectin Decreases the Total Body Burden: A Pilot Human Clinical trial
MCP was effective in decreasing the total body burden of Mercury in all subjects. MCP is a promising systemic gentle chelator of heavy metals that can be used on an on going basis. Percent Reduction in Mercury from Baseline 10 months4.5 months6 months 4 months 6.5 months Study Conclusion MCP Intervention Individual Results
The Role of Modified Citrus Pectin as an Effective Chelator of Lead in Children Hospitalized with Toxic Lead Levels Zhao ZY, Liang L, Fan X, Yu Z, Hotchkiss AT, Wilk BJ, Eliaz I Children’s Hospital, Zhejiang University, School of Medicine, Hangzhou, Republic of China Centrax International, Inc, San Francisco, CA, USA Eastern Regional Research Center, ARS, USDA, Wyndmoor, PA, USA EcoNugenics, Santa Rosa, CA, USA Altern Ther Health Med. 2008 14(4):34-8.
P Value = 0.0016 Lead in Blood Serum
P Value = 0.0007 Lead in 24 Hour Urine Excretion
Synergistic Benefits of MCP
Integrative blend of 33 ingredients: Vitamins, Minerals, Botanically Enhanced Medicinal Mushrooms, and Botanical Extracts Prostate Poly Botanical Formula
ProstaCaid Induces G2/M Cell Cycle Arrest & Apoptosis in Human & Mouse Androgen-Dependent & -Independent Prostate Cancer Cells Effects on long-term cell viability by colony formation Effects on cell viability on androgen- dependent, LNCaP (A) & CASP 2.1 (C), & androgen-independent PC3 (B) & CASP 1.1 (D) Yan J & Katz AE; Department of Urology, Columbia University Medical Center, New York, NY, USA. Integr Cancer Ther 2010 9:186-196.
Effect of ProstaCaid on Invasive Behavior of Prostate Cancer Cells AB CD uPA 0 20 40 80 ProstaCaid ( g/ml) 1.00 0.61 0.38 0.16 uPA Density (A) Cell adhesion. PC-3 cells were treated with ProstaCaid for 24 hours and cell adhesion to fibronectin determined. (B) Cell migration. Cell migration was determined after 24 hours of incubation with ProstaCaid in Boyden Chambers. (C) Cell invasion. Cell invasion was determined after 24 hours of incubation with ProstaCaid in Boyden Chambers coated with Matrigel. (D) uPA secretion. PC-3 cells were treated for 24 hours and the expression of uPA detected in conditioned media with anti-uPA antibody by Western blot. * p<0.05
ProstaCaid Inhibits Tumor Growth in a Xenograft Model of Human Prostate Cancer Results: No effect on body weight or activity of liver enzymes (ALT, AST). No sign of toxicity in liver, spleen, kidney, lung and heart Inhibition of tumor volumes (1024.6±378.6 vs. 749.3±234.3, P<0.001) qRT-PCR analysis showed significant up regulation of expression of CDKN1A (p21) and inhibition of expression of IGF2, NR2F2 and PLAU (uPA) Conclusion: ProstaCaid has significant anticancer activity in vivo with no signs of toxicity.
Prostate Polybotanical Formula
Contains botanicals, purified biologically active nutritional compounds and botanically enhanced medicinal mushrooms Breast Polybotanical Formula
Suppression of Proliferation & Invasive Behavior of Human Metastatic Breast Cancer Cells by Dietary Supplement BreastDefend Jiang J, Wojnowski R, Jedinak A, Sliva D; Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN, USA Department of Medicine, Indiana University. Cancer Center, School of Med., Indiana University, Indianapolis, IN, USA. Integr Cancer Ther 2011; Jun 10 (2):192 – 200.
Method: Highly aggressive triple negative human breast cancer cells (MDA-MB-231) implanted into the mammary gland in mice then given the formula orally (100 mg/kg of body weight) for four weeks. Results: The formula significantly decreased tumor growth and breast to lung metastasis, and did not affect body weight or activity of liver enzymes or show any sign of toxicity in liver spleen, kidney, lung and heart tissues in mice. – The cancer metastasized to the lungs in 67% of controls but only 20 percent of treated mice. The number of metastases per animal was also significantly affected by the formula. – Down-regulation of primary tumor genes PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor- 4). BreastDefend Suppresses MDA-MB-231 Growth and Breast-to-Lung Metastasis in a Orthotopic Tumor Model Jiang J, Thyagarajan-Sahu A, Loganathan J, Eliaz I, Terry C, Sandusky GE, Sliva D. Oncol Rep. 2012; 28: 1139-1145.
Breast Polybotanical Formula
Synergistic and Additive Effects of Modified Citrus Pectin with Two Novel Polybotanical Compounds, in the Suppression of Invasive Behavior of Human Breast and Prostate Cancer Cells Jiang J, Eliaz I, and Sliva D. Cancer Research Laboratory, MRI, Indiana University Health, Indianapolis, IN, USA Amitabha Med. Clinic & Healing Center, Sebastopol, CA, USA Depart. of Med., and Indiana Univer. Cancer Center, Indiana Univer. School of Med., Indianapolis, IN, USA. Integr Cancer Ther. 2013 March 12 (2):145-52.
* * * PC3 growth measured using MTT assay. Cells incubated for 24 hrs with ProstaCaid (ug/ml). *P <.05 Prostate Polybotanical Formula Effect on Proliferation of Human Prostate Cancer Cells
BA The invasive behavior of PC3 evaluated using migration assay in the presence of (A) MCP (mg/mL) & (B) MCP (mg/mL) plus Prostacaid (10 ug/mL). Prostate Formula & MCP Effect on Migration of Human Prostate Cancer Cells
* * * Breast Polybotanical Formula Effect on Proliferation of Human Breast Cancer Cells Growth of MDA-MB-231 measured using MTT assay. MDA-MB-231 cells incubated for 24 hrs with BreastDefend (ug/mL) at the indicated concentrations. *P <.05
B A Invasive behavior of MDA-MB-231 evaluated using migration assay in the presence of (A) MCP (mg/mL) & (B) MCP (mg/mL) plus BreastDefend (20 ug/mL). Breast Formula & MCP
Modified Citrus Pectin Published Data Summary Preclinical and Clinical Research Highlights on Modified Citrus Pectin
Preclinical Studies with MCP (17 Published Articles) *One in vitro study reported on both prostate and breast cancer (Glinskii OV, Huxley VH, Glinsky GV. et al. Neoplasia. 2005;7(5):522-527). **One article reported two in vivo studies and one in vitro study (Nangia-Makker P, Hogan V, Honjo Y, et al. J Natl Cancer Inst. 2002 Dec 18;94(24):1854-62). ***One articles reported both an in vivo and an in vitro study (Platt D, Raz A. J Natl Cancer Inst. 1992 Mar;84(6):438-42) In vitro (Type of Cancer)In vivo (Type of Cancer)Ex vivo (Type of Cancer) 5 (Prostate*)2 (Prostate) including 1 Lung Metastasis Study1 (Immune; Leukemia) 2 (Breast*,**)2 (Breast*,**) including 1 Lung Metastasis Study 1 (Angiosarcoma & Hemangiosarcom) 1 (Melanoma***)1 (Melanoma***) including 1 Lung Metastasis Study 3 (Colon**) including 1 Lymph and 1 Liver Metastasis Study 1 (Non Cancer; Small Intestine Permeability) 2 (Non Cancer; Kidney Injury, Arteriole Fibrosis) 9 Total10 Total2 Total
Human Clinical Study (Number of Participants ) Type of TrialResults Zhoa, et al., Altern Ther Health Med. 2008. (n = 7) Pilot trial: Lead toxicity in hospitalized children ages 5- 12 Very significant decrease in blood serum levels of lead (P =.0016) and very significant increase in 24-hour urine collection (P =.0007). No adverse effects. Azémar, et al., Clinical Medicine: Oncology. 2007. (n = 49) Pilot trial: To assess the quality of life, clinical benefit and antitumoral efficacy in advanced stage solid tumors (colorectal, prostate, breast, kidney, cervix/uterine, liver, pharynx, pancreatic, melanoma, stomach, bile duct carcinoma and chondrosarcoma) 22.5% patients showed a stable disease (SD) and 12.3% patients had a SD for a period longer than 24 weeks. One patient with metastasized prostate carcinoma showed a 50% decrease in serum PSA level after 16 weeks of treatment associated with a significant increase of clinical benefit, quality of life and decrease in pain. 20.7% patients had an overall clinical benefit response associated with a stabilization or improvement of life quality. All patients tolerated the therapy well without any severe adverse events. Eliaz, et al. Forsch Komplementmed. 2007. (n = 5) Case studies: Involving lowering of lead and mercury body burden 5 case studies presented show reduction in toxic heavy metals was achieved without side effects. Gradual decrease of total body burden is believed to have played an important role in recovery and health maintenance. Seven Clinical Studies with MCP
Human Clinical Study (Number of Participants) Type of TrialResults Eliaz, et al. Phytother Res. 2006. (n = 8) Pilot trial: Toxic heavy metal removal in healthy population In the first 24 hours the urinary excretion of arsenic increased significantly (p < 0.05). On day 6, urinary excretion was increased significantly for cadmium (p < 0.05). Lead showed a dramatic increase in excretion (p < 0.08), and mercury approached significance on day six. Other elements analyzed including essential elements did not show any significant change in excretion. Eliaz. 228th Annual American Chemistry Meeting. August 2004. (n = 5) Pilot trial: Decrease total body burden of mercury A significant decrease in total body mercury burden was seen in all participants. The decrease was found more significant over time. The mercury burden for the group dropped 68.32% (p=0.0313). All individual completed the study, and there were no side effects reported. Guess, et al. Prostate Cancer Prostatic Dis. 2003. (n = 13) Phase II pilot trial: Lengthening of PSA doubling time in biochemical relapsed prostate cancer patients. There were no serious side effects in any patient, but three patients withdrew from the study due to abdominal cramping or diarrhea. MCP was well tolerated by the remaining 10 evaluable patients. Seven (70%) of these evaluable patients had a significantly increased doubling time of PSA compared with their times before the treatment. Strum, et al. International Conference on Diet and Prevention of Cancer. May 1999. (n = 7) Pilot Study: Lengthening of prostate-specific antigen doubling time in biochemical relapsed prostate cancer patients. PSA doubling time was lengthened by more than 30% in 4/7 (57%) of patients. One patient had a partial response, one patient had stable disease, and one patient did not respond. No adverse effects were reported.
Galectin-3 Research The role of active biomarker galectin-3 in chronic disease progression
The PREVEND Study (Prevention of Renal and Vascular End-stage Disease) de Boer RA, van Veldhuisen DJ, R. T. Gansevoort RT, et al. The fibrosis marker Galectin-3 and outcome in the general population. J Intern Med. 2012 doi: 10.1111/j.1365-2796.2011.02476.x. University of Groningen, Groningen, The Netherlands
Overall Average 11.9 Galectin-3 Levels & Mortality from All Causes in the General Population: PREVEND
Galectin-3 in General Population: PREVEND (number of subjects = 7,968) CHARACTERISTIC Median Gal3 TOTAL 11.9 QUINTILE-1 7.7 QUINTILE-2 9.4 QUINTILE-3 10.9 QUINTILE-4 12.6 QUINTILE-5 15.6 P DM%3.62.3 220.127.116.11.000 MI18.104.22.168.74.27.40.000 Hypertension33.422.226.631.139.747.90.000 Stroke %0.90.80.6 1.31.60.004 Systolic BP 129.2±20.2125.0±18.1126.6±19.0128.6±19.6131.3±20.6134.9±22.5 0.000 Diastolic BP74.0±9.772.1 ±9.473.3±9.874.1±9.675.2±9.875.4±9.80.000
The COACH (Coordinating Study on Outcomes of Advising and Counseling in Heart Failure) Multicenter, randomized, controlled trial conducted in The Netherlands. A prospective sub-study was designed to evaluate Galectin-3 in patients with chronic heart failure and define cut-off levels for subsequent validation studies. Galectin-3 levels were measured in 582 banked EDTA-plasma samples.
COACH Galectin-3 Sub-Study Mortality from All Causes at 1 Year in Patients with CHF
COACH Galectin-3 Sub-Study Cardiovascular Mortality or Heart Failure-Related Hospitalization at 1 Year in Patients with CHF
DeFillipi et al, U.S. Cardiology, 7,1, 3–6 (2010) clearly indicate that circulating Galectin-3 is an important factor in fibrosis of many organs and organ systems, and that reducing circulating Galectin-3 may have an important role in remediating cardiac injury and progression to heart failure (HF). Similarly, Psarras et al, Eur. Heart J., April 26 (2011) demonstrate that reduction in Galectin-3 levels in the myocardium may reduce fibrosis in the heart and improve outlook. De Boer et al, Ann. Med., 43,1, 60–68 (2011) identify Galectin-3 as a key indicator in cardiac health. Shash et al, Eur J. Heart Fail., 12,8, 826–32 (2011) identify Galectin-3 levels as a key agent in heart failure through fibrosis. De Boer et al. Eur. J. Heart Fail., 11, 9, 811-817 (2009) link an increase in Galectin-3 expression and presence to heightened fibrosis, and heart failure. The same article links Galectin-3 to inflammation. Inflammation is the hallmark of arteriosclerosis, therefore Galectin-3 levels also contribute to coronary artery disease, peripheral artery disease, strokes, and vascular dementia. Galectin-3 and Cardiovascular Health
Modified Citrus Pectin Reduces Galectin- 3 Expression and Disease Severity in Experimental Acute Kidney Injury Kolatsi-Joannou M, Price KL, Winyard PJ, Long DA. Nephro- Urology Unit, UCL Institute of Child Health, London, UK PLoS ONE 2011 April 6(4): e18683.
Background: Folic acid (FA)-induced acute kidney injury model Method: Mice given 1% MCP-supplemented water, or plain water, 1 week before FA injection Results: During initial injury phase, all FA treated mice lost weight while their kidneys enlarged secondary to renal insult – Gross changes significantly lessened in MCP group – MCP clearly reduced renal cell proliferation – Recovery phase: MCP group showed decreased Galectin-3 expression with decreased renal fibrosis, macrophages, pro- inflammatory cytokine expression, and apoptosis MCP & Kidney Injury Study
Background: Aldosterone is involved in arterial stiffness and heart failure. Galectin-3 plays an important role in inflammation, fibrosis, and heart failure. MCP blocks Galectin-3 Methods and Results: Rats were treated with aldosterone combined with MCP for 3 weeks. Hypertensive aldosterone- treated rats presented vascular hypertrophy, inflammation, fibrosis, and increased aortic Gal-3 expression. Those also treated with MCP treatment abolished all the above effects. Conclusion: Galectin-3 is required for inflammatory and fibrotic responses to aldosterone in vascular smooth muscle cells in vitro and in vivo. By inhibiting Galectin-3, MCP prevents vascular fibrosis. Aldosterone Galectin-3 MCP Vascular Fibrosis Study
Test for Galectin-3 levels Address general inflammation & hyperviscosity Use MCP at appropriate dosages by: – Condition – Galectin-3 levels – Therapeutic goal Elevated Galectin-3: What can we do?
Serum Galectin-3 Testing Serum Galectin-3 Testing USFDA approved blood test that measures Galectin-3 for Cardiovascular Disease
Galectin-3 Levels: Reference Ranges Galectin-3 levels > 17.8 ng/ml are considered to be an extreme risk factor of mortality. Ideal levels are < 14 ng/ml in the general population. For cancer and cardiac patients, ideal levels are < 12 ng/ml. Galectin-3 levels change in 20% of population every 3 months. Repeated testing is important.
Desired levels <12.0 ng/ml Follow up on Galectin-3 levels routinely every 3-6 months Galectin-3 Levels: Cancer
Levels <17.8, or not tested MCP 15g daily Levels >17.8 MCP 20 - 25g daily Active Cancer
Levels < 12.0 ng/ml MCP 5g daily Levels = 12.0 – 14.0 ng/ml MCP 10g daily Levels = 14.0 – 17.8 ng/ml MCP 15g daily Levels >17.8 ng/ml MCP 20 – 25g daily Cancer Long Term Maintenance (3 years post therapy)
Galectin-3 Levels: MCP Dosage (grams)
Galectin-3 is a novel, active biomarker that is both a cause of multiple diseases and a diagnostic and prognostic biomarker. Modified Citrus Pectin is a proven natural Galectin-3 blocker. In Conclusion: Galectin-3 and Modified Citrus Pectin