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Important note for readers:
while many of the scientific discoveries and clinical developments listed in
this section are extremely exciting, they are stepping stones in the studies
of Diindolylmethane (DIM) and some of the other key natural ingredients in
ActivaMune. The exploration of clinical applications for Diindolylmethane is
an emerging science. Only the US FDA has the authority to recognize a compound as a
drug or therapeutic for a particular condition in the US and that only
occurs after the compound has been thoroughly studied and its efficacy
established in four consecutive human clinical trials. At this point in
time, Diindolylmethane and the other natural ingredients in ActivaMune are
regarded as dietary supplements and not therapeutics for any specific
condition by the US FDA. ActivaMune is a nutritional supplement. The
statements on this website have not been evaluated by the US Food and Drug
Administration. ActivaMune is not intended to diagnose, treat, cure or
prevent any disease.
Phase I human clinical studies of Diindolylmethane (DIM) as a therapeutic
candidate for castrate-resistant non-metastatic prostate cancer patients
demonstrated efficacy. DIM has now progressed to Phase II human clinical
studies. The recommended dosage for the Phase II study is approximately 2x
the DIM concentration in ActivaMune.
(In order for a therapeutic candidate to receive recognition as a treatment
for a particular condition by the US FDA, it must pass four progressive
phases of human clinical trials. DIM is currently regarded as a dietary
supplement and not a therapeutic for any condition.)
A phase I dose-escalation study of oral DIM (3,3'-Diindolylmethane) in
castrate-resistant, non-metastatic prostate cancer.
Am J Transl Res. 2010 Jul 23;2(4):402-11. Heath EI, Heilbrun LK, Li
J, Vaishampayan U, Harper F, Pemberton P, Sarkar FH. Karmanos Cancer
Institute, Wayne State University Detroit, MI, USA.
In a landmark preclinical study at UC Berkeley, Diindolylmethane (DIM) is shown to
promote cellular prostate health.
UC Berkeley Publication.
3,3'-Diindolylmethane induces a G(1) arrest in human
prostate cancer cells irrespective of androgen receptor and p53 status.
Biochemical Pharmacology. 2009 Sep 1;78(5):469-76. Epub 2009
May 9. Vivar OI, Lin CL, Firestone GL, Bjeldanes LF.
Department of Nutritional Sciences and Toxicology, University of California,
Berkeley, 94720-3104, USA.
Scientists at the Barbara Ann Karmanos Cancer
Institute publish their findings regarding Diindolylmethane (DIM) and its
potential as a dietary supplement. Cancer Treatment
Review. 2009 Aug 4. Harnessing the fruits of nature for the development of
multi-targeted cancer therapeutics. Sarkar FH, Li Y. Department of
Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University
School of Medicine, Detroit, MI, USA.
In a breakthrough preclinical study, biomedical investigators at the Genomics Institute of Novartis
Research Foundation elucidate a novel biological property of
Diindolylmethane (DIM) and its relevance to cardiovascular health. Lipid G
protein-coupled receptor ligand identification using beta-arrestin
PathHunter assay. Journal of Biological Chemistry 2009 May
1;284(18):12328-38. Epub 2009 Mar 13. Yin H, Chu A, Li W, Wang B, Shelton F,
Otero F, Nguyen DG, Caldwell JS, Chen YA. Genomics Institute of the Novartis
Research Foundation, San Diego,
California 92121, USA.
Diindolylmethane (DIM) is a potent activator of the immune response system in-vivo
- UC Berkeley Publication.
Scientists demonstrate for the first time that DIM modulates four key
cytokines in-vivo:
Interferon-Gamma (IFN-G), Granulocyte
Colony Stimulating Factor (G-CSF),
Interlukin-12 (IL-12),
and
Interlukin-6 (IL-6).
IFN-G is responsible for the entire immune
response system. G-CSF is responsible for White Blood
Cell production in the body. IL-6 is responsible for the body's direct
anti-bacterial response. IL-12 stimulates the growth and function of T-Cells
which help to fight off pathogens. This key publication marks the birth of a global
effort to study DIM as a potent natural therapeutic candidate for most forms of
cancer, most viral infections and most bacterial infections. According to Dr. Gary Firestone,
Director of the National Institutes of Health Cancer Research Program and
co-author of the study at UC Berkeley, "This study shows that there is a whole new universe
of molecular biology related to DIM....there are no other agents
known that can both directly promote apoptosis and
enhance the function of the immune system at the same time."
3,3′-Diindolylmethane stimulates murine immune
function in vitro and in vivo, Xue
L, Pestka J, Maoxiang L, Firestone GL, Bjeldanes LF, Journal of
Nutritional Biochemistry, published
online, 8-20-07. Department of Nutritional Sciences and Toxicology,
University of California, Berkeley, 94720-3104, USA.
Diindolylmethane (DIM)
activates and potentiates interferon-gamma signaling in human cells - UC
Berkeley Publication.
Activation and potentiation of
interferon-gamma signaling by 3,3'-diindolylmethane in MCF-7 breast cancer
cells.
Molecular Pharmacology. 2006 Feb;69(2):430-9.
Riby JE, Xue L, Chatterji U, Bjeldanes EL, Firestone GL, Bjeldanes LF.
Department of Nutritional Sciences and Toxicology, University of California,
Berkeley, 94720-3104, USA.
Diindolylmethane (DIM) stimulates Interferon-Gamma gene expression in human cells - UC Berkeley
Publication.
DIM stimulates IFNgamma gene expression in
human breast cancer cells via the specific activation of JNK and p38
pathways.
Xue L,
Firestone GL, Bjeldanes LF. Department of Nutritional Sciences and
Toxicology, University of California, Berkeley, CA
94720-3104, USA. Oncogene. 2005 Mar 31;24(14):2343-53.
Diindolylmethane (DIM) supplementation in humans increases the 2-hydroxylation of estrogen
metabolites - UC Berkeley
Publication. As 2-hydroxylation of estrogen metabolites is a
process that scientists believe
helps to reduce the risk of breast and prostate cancer, this human clinical
study on DIM's effect on estrogen metabolites made headline news world-wide and added to the
popularity of DIM as a nutritional supplement. Pilot study: effect of
3,3'-diindolylmethane supplements on urinary hormone metabolites in
postmenopausal women with a history of early-stage breast cancer.
Journal of
Nutrition and Cancer. 2004;50(2):161-7. Dalessandri KM,
Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF Department of
Molecular and Cell Biology, University of California, Berkeley, 94720-3200,
USA.
Biomedical researchers in
Europe and the United States, after studying over 10,000 women, confirm that
2-hydroxylation of estrogen metabolites reduces the risk of breast
cancer. Estrogen metabolism
and risk of Breast cancer: A prospective study of the 2:16α-hydroxyestrone
ratio in premenopausal and postmenopausal women.
Epidemiology, 2000, vol. 11, no6,
pp. 635-640 Muti P, Bradlow HL, Micheli A, Krogh V, Freudenheim JL,
Schunemann HJ, Stanulla M, Jun Y, Sepkovic DW, Trevisan M, Berrino F.
Department of Social and Preventive Medicine, University at Buffalo, State
University of New York at Buffalo, Buffalo, NY, USA, Epidemiology Division
of the National Cancer Intitute (Istituto Nazionale Tumori), Milan, Italy,
Department of Pediatric Hematology and Oncology, Medical School of Hannover, Hannover,
Germany.
A preclinical study shows that Diindolylmethane (DIM) synergizes with Paclitaxel (Taxol) - Thomas Jefferson
University Publication. Biomedical investigators at the Jefferson Medical
College have demonstrated that DIM synergizes with the number one selling
cancer drug worldwide, Paclitaxel (Taxol)--a phytochemical extracted from
the Pacific Yew Tree. Their paper was published in the Journal of Surgical
Research. 3,3′-Diindolylmethane and Paclitaxel Act Synergistically to
Promote Apoptosis in HER2/Neu Human Breast Cancer Cells. Journal of
Surgical Research, 2006
May 15;132(2):208-13.
K. McGuire, N. Ngoubilly, M. Neavyn,
S. Lanza-Jacoby Department of Surgery, Jefferson Medical
College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
Biomedical scientists find that cruciferous vegetable intake reduces
the risk of late stage prostate cancer by up to 52%.
Prospective Study of Fruit and Vegetable Intake and Risk
of Prostate Cancer. Journal of the National Cancer Institute.
2007 Jul 24; (Epub ahead of print) Krish VA,
Peters U, Mayne ST, Subar AF, Chatterjee N, Johnson CC, Hayes RB.
Click
here for the BBC Report covering this publication.
Biomedical investigators publish their findings linking high Brassica
vegetable consumption with a 40% reduction in the risk of breast cancer
development.
Brassica Vegetables and Breast Cancer Risk. Terry P,
Wolk A, Persson I, Magnusson C, (2001). JAMA 285 (23): 2975-2976.
A preclinical study at UC Berkeley demonstrates that Diindolylmethane
(DIM) promotes cellular breast health - UC
Berkeley Publication. 3,3'-Diindolylmethane (DIM) induces a G(1) cell
cycle arrest in human breast cancer cells that is accompanied by
Sp1-mediated activation of p21(WAF1/CIP1) expression. Hong C, Kim HA,
Firestone GL, Bjeldanes LF. Carcinogenesis. 2002
Aug;23(8):1297-305. Department of Nutritional Sciences and
Toxicology, University of California, Berkeley, CA 94720, USA.
Broccoli sprouts found to boost
the body's ability to eliminate toxins in human study by investigators at
the Johns Hopkins School of Medicine.
Cancer Epidemiology Biomarkers and Prevention. 2005 Nov. 14
:2605-13. Effects of glucosinolate-rich broccoli sprouts on
urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a
randomized clinical trial in He Zuo township, Qidong, People's Republic of
China. Talalay P, Fahey JW. Department of Environmental Health Sciences,
Bloomberg School of Public Health, Johns Hopkins University, Room E7541, 615
North Wolfe Street, Baltimore, MD 21205, USA
US medical researchers publish findings linking Calcium and Vitamin D3
intakes with up to a 77% reduction in cancer risk relative to placebo
controls.
Vitamin D and Calcium supplementation reduces cancer risk: results of a
randomized trial. American Journal of Clinical Nutrition. 2007
Jun:85(6): 1586-91. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR,
Heaney RP.
Osteoporosis Research Center, Creighton University, Omaha, NE
68131, USA.
Molecular biologists publish findings that Vitamin D3 boosts the
immune system by promoting the production of
cathelicidin antimicrobial peptides. Human cathelicidin antimicrobial peptide (CAMP) gene
is a direct target of the vitamin D receptor and is strongly up-regulated in
myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005
Jul;19(9):1067-77. Gombart AF, Borregaard N, Koeffler HP. Department of
Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, David
Geffen School of Medicine at UCLA, Los Angeles, California 90048, USA
Scientists discover that selenium blocks
NFkB activity. NFkB inhibits
apoptosis and promotes inflammation. High selenium reduces NF-kappaB-regulated
gene expression in uninduced human prostate cancer cells. Christensen MJ,
Nartey ET, Hada AL, Legg RL, Barzee BR, Journal of Nutrition and Cancer,
2007;58(2):197-204.
Department of Nutrition, Dietetics, and Food Science, Brigham
Young University, Provo, UT 84602, USA.
United States Department of Agriculture scientists
publish an
important
review of selenium as a nutrient. Selenium as an anticancer
nutrient: roles in cell proliferation and tumor cell invasion. Zeng H,
Combs GF Jr., 2007 Jun 22, Journal of
Nutritional Biochemistry. United States
Department of Agriculture, Agricultural Research Service, Grand Forks Human
Nutrition Research Center, P.O. Box 9034, Grand Forks, ND 58202-9034, USA.
Researchers at Johns
Hopkins determine that women with low serum selenium and total carotenoids
have higher mortality rates--a publication of the Women's Health and Aging
Studies. Journal of Nutrition. 2006 Jan;136(1):172-6.
Ray AL, Semba RD, Walston J., Ferrucci L, Cappola AR, Ricks MO, Xue QL,
Fried LP. The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Researchers at the German Institute of Human
Nutrition determine that
the
association of decreased cancer risk with intake of cruciferous vegetables
and selenium is stronger than that reported for fruits and vegetables in
general. From dietary antioxidants
to regulators in cellular signaling and gene regulation: Sulforaphane and
selenium, partners in adaptive response and prevention of cancer.
Free Radical Research.
2006 Aug;40(8):775-87. Brigelius-Flohe R., Banning A. German
Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114
- 116, D-14558, Nuthetal, Germany.
Researchers in the UK
demonstrate that selenium and sulforaphane synergize in their antioxidative
activity.
Synergy between sulforaphane and selenium in the induction
of thioredoxin reductase 1 requires both transcriptional and translational
modulation.
Carcinogenesis, 2003
Mar;24(3):497-503. Nutrition Division,
Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
Zhang J, Svehikova V., Bao Y, Howie AF, Beckett GJ, Williamson G.
Click
here for the BBC Report covering this publication.
A landmark
preclinical nutrition study shows that a combined diet of broccoli and
tomatoes has significant health promoting effects on prostate cells.
Combinations of Tomato and Broccoli Enhance
Antitumor Activity in Dunning R3327-H Prostate Adenocarcinomas. Canene-Adams
K, Lindshield B, Wang S, Jeffery E, Clinton S, Erdman J.,
Cancer Research 2007; 67: (2). January 15,
2007
Groundbreaking clinical trial demonstrates that selenium supplementation can
help support the immune system. Suppression of human
immunodeficiency virus type 1 viral load with selenium supplementation: a
randomized controlled trial. Archives
of Internal Medicine.
2007 Jan 22;167(2):148-54. Hurwitz BE, Klaus JR, Lllabre MM, Gonzalez A,
Lawrence PJ, Maher KJ, Greenson JM, Baum MK, Shor-Posner G, Skyler JS,
Schneiderman N.
Scientists at the University
of California, San Diego publish findings regarding selenium's immune
enhancing properties. Selenium in the maintenance and
therapy of HIV-infected patients. Chemical and Biological Interactions.
1994 Jun;91(2-3):199-205.
Schrauzer GN, Sacher J. University of California, San Diego,
Department of Chemistry and Biochemistry, La Jolla 92093.
Seminal epidemiology study conducted by researchers at the
Massachusetts Eye and Ear Infirmary establishes a direct link between higher
intakes of Lutein and Zeaxanthin and vision health.
Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular
degeneration. Eye Disease Case-Control Study Group. Journal of the
American Medical Association.1994 Nov 9;272(18):1413-20.
Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD,
Gragoudas ES, Haller J., Miller DT. Epidemiology Unit, Massachusetts
Eye and Ear Infirmary, Boston 02114.
British biomedical researchers
report that supplementation with the carotenoids Lutein or Zeaxanthin
improves human visual performance. Study Title: supplementation with the
carotenoids lutein or zeaxanthin improves human visual performance. Ophthalmic & Physiological
Optics. Kvansakul J, Rodriguez-Carmona M., Edgar DF, Barker FM, Kapcke W.,
Schalch W., Barbur JL. Applied Vision Research Centre, Department of
Optometry and Visual Science, City University, London, UK.
Canadian biomedical researchers announce
epidemiological evidence linking increased Lycopene intake to the reduction
of oxidative stress. Lycopene.
Advances in Food and Nutrition Research 2006;51:99-164. Rao
AV, Ray MR, Rao LG, Department of Nutritional Sciences, Faculty of
Medicine, University of Toronto, Toronto, Ontario, Canada.
Researchers at Tufts University
publish the relationship between Vitamin E intake and enhanced immune
function.
Vitamin E and immune
response in the aged: molecular mechanisms and clinical implications.
Immonology Reviews. 2005 June;205:269-84. Meydani SN, Han SN, Wu D.
Nutritional Immunology
Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at
Tufts University, Boston, MA 02111, USA
Scientists at the Johns Hopkins School of Medicine
publish an important study regarding sulforaphane and its promotion of
gastrointestinal health - Sulforaphane inhibits
extracellular, intracellular, and antibiotic-resistant strains of
Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors.
2002 May 28;99(11):7610-5. Proclamation of the National Academy of Sciences.
Fahey JW, Haristoy X, Dolan PM, Kensler TW,
Sholtus I, Stephenson KK, Talalay P, Lozniewski A. Lewis B. and Dorothy
Cullman Cancer Chemoprotection Center, Department of Pharmacology and
Molecular Sciences, The Johns Hopkins University School of Medicine, 725
North Wolfe Street, Baltimore, MD 21205-2185, USA.
Dr.
Leonard Bjeldanes and Dr. Gary Firestone of UC Berkeley publish an important
study elucidating the molecular biology of Diindolylmethane (DIM).
Cytostatic effects of 3,3'-diindolylmethane in human endometrial cancer
cells result from an estrogen receptor-mediated increase in transforming
growth factor-alpha expression. Carcinogenesis.
2001 Nov;22(11):1809-17. Leong H, Firestone, GL, Bjeldanes LF.
Department of Nutritional Sciences and Toxicology, University of
California-Berkeley, Berkeley, CA 94720, USA.
