Study finds blood sugar levels linked to cancer and death risk

Findings from the Korean Cancer Prevention Study published in the January 12, 2005, issue of the Journal of the American Medical Association revealed an association between having elevated blood sugar and diabetes and the risk of developing and dying from cancer, as well as with all cause mortality.

Assistant professor of epidemiology Sun Ha Jee, PhD, of the Graduate School of Public Health, Yonsei University, Seoul, Korea, and colleagues followed 1,298,385 Koreans aged 30 to 95 for ten years. The study population consisted of 829,770 men and 468,615 women. Participants were employees of an Insurance Corporation that provided medical evaluations to their workers every two years. Questionnaires assessed medical history and health habits, and fasting blood glucose was measured during routine blood tests. The participants were followed for ten years, during which the incidence of cancer and deaths associated with the disease were tracked.

After ten years 20,566 men and 5,907 women had died of cancer. Cancer risk was similar to the risk of dying from the disease in this population. Individuals who had diabetes, or those without the disease whose fasting blood sugar levels were elevated had a greater risk of developing or dying from cancer than those with normal blood sugar. Men and women whose fasting blood sugar levels were greater than 140 milligrams per deciliter (mg/dL) at the beginning of the study had a respective 29 and 23 percent higher death rate from all cancers compared to men and women whose blood glucose was less than 90 mg/dL. The risk was the greatest for pancreatic cancer, with high blood glucose levels nearly doubling the risk in men and more than doubling the risk in women. Significant associations were also found for other types of cancer.

When all-cause mortality was examined, fasting glucose levels were found to be positively associated with the 54,385 deaths that occurred. Subjects whose glucose was greater than or equal to 140 mg/dL had more than double the rate of death during the study period than that of subjects whose blood sugar was lower than 90 mg/dL.

The authors explained that glucose intolerance could be one way that obesity increases cancer risk. Dr Jee commented, "This study provides more information on glucose intolerance, an emerging cause of cancer. It points to increased cancer risk as another adverse consequence of rising obesity around the world."



Protocol
Cancer adjuvant therapy
Tumors are primarily obligate glucose metabolizers, meaning they require sugar for survival. Even though the brain normally uses high amounts of glucose, hepatomas (a tumor of the liver) and fibrosarcomas (a sarcoma that contains fibrous connective tissue) consume roughly as much glucose as the brain. Some Americans continuously satisfy cancer's appetite, ingesting as much as 295 pounds of sugar a year.

Nobel laureate Otto Warburg, Ph.D., discovered in 1955 that cancer cells use glucose for fuel. But glucose accomplishes another strategic maneuver that strongly favors the cancer: it immobilizes internal defenses, the actions of the immune system. A study involving 10 healthy human volunteers assessed fasting blood glucose levels and the phagocytic index of neutrophils, a type of white blood cell. Glucose, fructose, sucrose, honey, and orange juice all significantly decreased the capacity of neutrophils to engulf bacteria. A diet structured away from sugars deprives cancer of its energy and increases the reliability of the immune response.

Dr. Jeff Bland advises selecting foodstuffs low on the glycemic index to avoid gratifying the tumor's appetite. The glycemic index lists the relative speed at which different foods are digested and raise blood sugar levels. Each food is compared to the effect of the same amount of pure glucose on the body's blood sugar curve. Glucose itself has a glycemic index rating of 100. Foods that are broken down and raise blood glucose levels quickly have higher ratings. The closer to 100, the more the food resembles glucose. The lower the rating, the more gradually that food affects blood sugar levels.

The diseases such as obesity and diabetes mellitus (often characterized by hyperinsulinemia) are associated with an increased risk of endometrial, colorectal, and breast cancers. The mechanisms underlying insulin-mediated neoplasias appear to include enhanced DNA synthesis (with the resultant tumor cell growth), inhibited apoptosis, and an altered sex hormone milieu. The reduced insulin levels seen with physical activity, weight loss, and a high fiber diet may in fact account for the decreased cancer incidence observed in individuals who maintain normal glucose and insulin levels (Gupta et al. 2002).

http://www.lef.org/protocols/prtcl-027.shtml

I hope you do not mind my adding this to renforce your post.

***************************************
Below is a bunch of references that I have collected about cancer and sugar, and about Otto Warburg.
***************************************

Otto Warburg, "On The Origin of Cancer Cells," SCIENCE, (24FEB1956), Volume 123,
Number 3191, pp. 309-314.

*** web sites referring to Otto Warburg ****

Otto Warburg – Biography at The Nobel Foundation web site.
http://nobelprize.org/medicine/laur...arburg-bio.html

Warburg, Otto
Encyclopedia Britannica Article
http://www.britannica.com/eb/article-9076088

Cancer's Sweet Tooth
by Patrick Quillin, PHD, RD, CNS…from the book "Beating Cancer with Nutrition"
http://www.annieappleseedproject.org/cansweettoot.html
[About 2/3 the way down the page is the following]
In Europe, the "sugar feeds cancer" concept is so well accepted that oncologists, or cancer doctors, use the Systemic Cancer Multistep Therapy (SCMT) protocol.

Cancer Loves Sugar
http://www.mnwelldir.org/docs/nutrition/sugar.htm
[At beginning]Every doctor learned back in medical school all about Otto Warburg's discovery; a discovery of humongous proportions, because way back in the thirties Otto discovered the main biochemical cause of cancer, or what differentiates a cancer cell from a normal, healthy cell. So big a discovery was this, that Otto Warburg was awarded the Nobel Prize. [At very end]Then there are the food therapies: aimed at starving cancer. Knowing what cancer loves, the patient avoids them. Cancers loves cooked foods (this is a relatively recent finding) and cancer loves sugar. If you hate your cancer, then starve it.

The Origin of Cancer Cells
http://www.prostate90.com/sci_papers/warburg.html
[In fifth paragraph]Otto Warburg, won his first Nobel Prize in 1931 for the oxygen transferring enzyme of cell respiration and his second Nobel Prize in 1944 for his discovery of the hydrogen transferring enzyme. His discoveries are quoted above and as follows: "But, even for cancer. there is only one primary cause. Summarized in a few words, the cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar." [My reading indicates that cancer continues to be anaerobic EVEN in the presence of sufficient oxygen, so it is not an oxygen deficiency but a metabolic abnormality in cancer cells.]

REVERSING CANCER A Journey from Cancer to Cure by Dr. Gerald H. Smith
http://www.icnr.com/articles/rvcannounce.html
ghsdoc~icnr.com
[about 2/3 the way down the page at a heading titled "Real Cause of Cancer"]Cancer has only one prime cause. It is the replacement of normal oxygen respiration of the body's cells by an anaerobic [i.e., oxygen-deficient] cell respiration. -Dr. Otto Warburg-1931 Nobel Prize-Winner [Warburg's hypothesis on the cause is generally considered wrong. BUT the effect he described of anaerobic respiration is accepted as fact.]

HOW TO RECOVER FROM CANCER By Dr. James Howenstine, MD. March 20, 2004
http://www.newswithviews.com/Howenstine/james8.htm
jimhow~racsa.co.cr
[At the beginning of the page is-] Nobel Prize winner, Dr. Otto Warburg, discovered that he could produce cancer almost at will by lowering the oxygen level of tissues by 35 %. Tissues with low oxygen content are acidotic and raising the ph with alkalinizing therapy greatly increases the oxygen content of the tissue causing cancer to disappear. [That cancer tumors are very acidic is known, but it is not clear that this condition can be altered in as direct manner as the doctor claims.]

*** PubMed abstracts referring to the Warburg Effect ****

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=16025159
[Last line of abstract]Moreover, the PFKFB4 and PFKFB3 gene expression in
mammary gland cancer cells has also a significant role in the Warburg effect which is found in all malignant cells.

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15967109
[First line of abstract]Metastatic tumors generally exhibit aerobic glycolysis (the Warburg effect).

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15695406
[End of abstract]Our study shows a promising therapeutic strategy to
effectively kill cancer cells and overcome drug resistance. Because the
Warburg effect and hypoxia are frequently seen in human cancers, these findings may have broad clinical implications.

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=11943784
[End of abstract]Cancer cells display high rates of aerobic glycolysis, a phenomenon known historically as the Warburg effect.

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15601632
Energy Boost: The Warburg effect Returns in a New Theory of Cancer Garber
J Natl Cancer Inst.2004; 96: 1805-1806.


1: Novartis Found Symp. 2001;240:251-60; discussion 260-4.

'The metabolism of tumours': 70 years later.

Semenza GL, Artemov D, Bedi A, Bhujwalla Z, Chiles K, Feldser D, Laughner E,
Ravi R, Simons J, Taghavi P, Zhong H.

Institute of Genetic Medicine, Department of Medicine, The Johns Hopkins
University School of Medicine, Baltimore, Maryland 21287, USA.

Otto Warburg's classic treatise on the reprogramming of tumour metabolism from oxidative to glycolytic metabolism was published in London in 1930. Although the Warburg effect is one of the most universal characteristics of solid tumors, the molecular basis for this phenomenon has only recently been elucidated by studies indicating that increased expression of genes encoding glucose transporters and glycolytic enzymes in tumour cells is mediated by the transcription factors c-MYC and HIF-1. Whereas c-myc is a direct target for oncogenic mutations, expression of hypoxia-inducible factor 1 (HIF-1) is indirectly up-regulated via gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes that result increased HIF-1alpha protein expression and/or increased HIF-1 transcriptional activity in a cell-type-specific manner. As a result of genetic alterations and intratumoral hypoxia, HIF-1alpha is overexpressed in the majority of common human cancers relative to the surrounding normal tissue. In human breast cancer and brain tumors, HIF-1alpha overexpression is strongly correlated with tumour grade and vascularity.

Publication Types:
Review
Review, Tutorial

PMID: 11727934 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=11727934

2: Cancer Res. 2002 Nov 15;62(22):6674-81.

The bioenergetic signature of cancer: a marker of tumor progression.

Cuezva JM, Krajewska M, de Heredia ML, Krajewski S, Santamaria G,
Kim H, Zapata JM, Marusawa H, Chamorro M, Reed JC.

Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa,
Universidad Autonoma de Madrid-Consejo Superior Investigaciones Cientificas,
Universidad Autonoma de Madrid, 28049 Madrid, Spain. jmcuezva~cbm.uam.es

Mitochondrial H+-ATP synthase is required for cellular energy provision and for efficient execution of apoptosis. Almost one century ago, Otto Warburg proposed the hypothesis that mitochondrial function might be impaired in cancer cells. However, his hypothesis was never demonstrated in human carcinomas. In this study, we have analyzed the expression of the beta-catalytic subunit of the H+-ATP synthase (beta-F1-ATPase) of mitochondria in carcinomas of the human liver, kidney, and colon. We show that carcinogenesis in the liver involves a depletion of the cellular mitochondrial content, as revealed by reduced content of mitochondrial markers, whereas in kidney and colon carcinomas, it involves a selective repression of the expression of the beta-F1-ATPase concurrent with an increase in the expression of the glycolytic glyceraldehyde-3-phosphate dehydrogenase. Both mechanisms limit mitochondrial cellular activity in cancer, strongly supporting Warburg's hypothesis, and suggest a mechanism for the resistance and compromised apoptotic potential of tumor cells. Furthermore, we show that the metabolic state of the cell, as defined by a bioenergetic mitochondrial index relative to the cellular glycolytic potential, provides a signature of carcinogenesis of prognostic value in assessing the progression of colorectal carcinomas.

PMID: 12438266 [PubMed - indexed for MEDLINE]

http://cancerres.aacrjournals.org/c...full/62/22/6674

3: Cancer Res. 2003 Jul 15;63(14):3847-54.

The glycolytic phenotype in carcinogenesis and tumor invasion:
insights through mathematical models.

Gatenby RA, Gawlinski ET.
Department of Radiology, The University of Arizona,
Tucson, Arizona 85724-5067, USA.
rgatenby~radiology.arizona.edu

Malignant cells characteristically exhibit altered metabolic patterns when compared with normal mammalian cells with increased reliance on anaerobic metabolism of glucose to lactic acid even in the presence of abundant oxygen. The inefficiency of the anaerobic pathway is compensated by increased glucose flux, a phenomenon first noted by Otto Warburg approximately 80 years ago and currently exploited for 2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging in clinical radiology. The latter has demonstrated the glycolytic phenotype is a near-universal phenomenon in human cancers. The potential role of the glycolytic phenotype in facilitating tumor invasion has been investigated through mathematical models of the tumor-host interface. Modified cellular automaton and diffusion reaction models demonstrate protons will diffuse from the tumor into peritumoral normal tissue subjecting nontransformed cells adjacent to the tumor edge to an extracellular pH significantly lower than normal. This leads to normal cell death via p53-dependent apoptosis pathways, as well as degradation of the interstitial matrix, loss of intercellular gap junctions, enhanced angiogenesis, and inhibition of the host immune response to tumor antigens. Transformed cells maintain their proliferative capacity in acidic extracellular pH because of mutations in p53 or some other component in the apoptosis pathways. This allows tumor cells to remain proliferative and migrate into the peritumoral normal tissue producing the invasive phenotype. Mathematical models of invasive cancer based on tumor-induced acidification are consistent with extant data on tumor microenvironment and results from clinical positron emission tomography imaging, including the observed correlation between tumor invasiveness and glucose utilization. Novel treatment approaches focused on perturbation of the tumor microenvironment are predicted from the mathematical models and are supported by recent clinical data demonstrating the benefits of azotemia and metabolic acidosis in survival of patients with metastatic renal cancer. The evolutionary basis for adoption of the glycolytic phenotype during carcinogenesis remains unclear because it appears to confer significant competitive disadvantages on the tumor cells due to of inefficient energy production and expenditure of resources to remove the acid byproducts. We propose that the glycolytic phenotype represents a successful adaptation to environmental selection parameters because it confers the ability to invade. That is, the glycolytic phenotype allows the cell to move from the microenvironment of a premalignant lesion to adjacent normal tissue. There it competes with normal cells that are less fit than the populations within the tumor in a microenvironment of relative substrate abundance. The consequent unrestrained proliferation allows the glycolytic phenotype to emerge simultaneous with the transition from a premalignant lesion to an invasive cancer.

PMID: 12873971 [PubMed - indexed for MEDLINE]

http://cancerres.aacrjournals.org/c...full/63/14/3847

4: Proteomics. 2004 Sep;4(9):2789-95.

Mitochondrial proteome: cancer-altered metabolism associated
with cytochrome c oxidase subunit level variation.

Krieg RC, Knuechel R, Schiffmann E, Liotta LA, Petricoin EF 3rd, Herrmann PC.

Institute of Pathology, UKAachen der RWTH, Aachen, Germany.

Shifts in metabolism associated with tumorigenesis were first noted by Otto Warburg in the 1920s. In the ensuing decades many examples of the phenomenon have been elucidated while the underlying molecular mechanism has remained elusive. As the enzyme complex at the crux of oxidative phosphorylation, cytochrome c oxidase is uniquely positioned to have a very high impact on cellular metabolism. In this study, we test the hypothesis that there is a specific association between altered cytochrome c oxidase subunit levels and altered metabolism by combining the technique of reverse-phase protein microarray with radiolabeled glucose metabolic studies. Such a relationship is observed with five different cell lines, two of which (1542N and 1542T) are a matched set of normal and tumor-based lineages derived from the same prostate gland. By measuring the [(14)C]carbon dioxide production of a cell line metabolizing [1-(14)C]glucose and comparing those measurements to values obtained for the same cell line metabolizing [6-(14)C]glucose, we determined the relative utilization of the hexose monophosphate shunt and glycolysis progressing through the Krebs cycle metabolic pathway in each cell line. In all cases there is an increased utilization of hexose monophosphate shunt relative to glycolysis progressing through the Krebs cycle in tumor derived relative to normal derived cell lines. Additionally, there is an associated increase in the ratio of nuclear encoded cytochrome c oxidase subunits to mitochondrially encoded cytochrome c oxidase subunits in the tumor-derived cell lines. These results demonstrate an alteration in subunit levels of a single enzyme complex (cytochrome c oxidase) commensurate with tumor-altered metabolism.

PMID: 15352252 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15352252
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Larry - You The Man!

I thought that this link existed - but I did not know there was any scientific evidence to prove the link.

It dumb founds me that medical experts can know that sugar causes cancer, type 2 diabetes, heart attack, stroke, etc -- but not education its citizens like they do on cigarettes, drugs, and alcohol.

Since my father died of Prostate Cancer when I was only 20, he was just 58, perhaps you can forgive my TOTAL cynicism in the following comments.

OF COURSE, the medical INDUSTRY does NOT tell about the link! Think of ALL THE MONEY they would loose if they were to say, "cancer can be cured by total restriction of carbohydrates." (And, you would also need some other dietary changes.) And what would the sugar lobby say to that? They would "have a COW" and threaten to sue the AMA and anyone else they could to protect their profits.

And such a declaration would be UNpopular with the drug manufactures. The people that fund MOST of the research needed to validate such a claim for curing cancer. So just like research on fats, the research on the cancer sugar connection is not getting funded the way it needs to be to prove the connection.

Which leads me to believe -- that once America wakes up -- lawsuits against doctors, hospitals, pharma companies, AMA, FDA, etc -- are going to make the tobacco lawsuits look like "chump change".

Everything below can be found at pubmed.gov (which is all you need type and
you arrive at)
http://www.ncbi.nlm.nih.gov:80/entr....fcgi?db=PubMed
by putting the following in to the search box you will get the hits listed below the search list.

cancer[Text Word] AND copper[Text Word]

Zinc deficiency, DNA damage and cancer risk.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15542347
The first sentence in this is very signifant in view of the stand of the AMA
over the years, that nutrition has no role in disease.

The sugar link is harder to get good research on. I suspect that it is in part because
who wants to fund research that would show that you can stop cancer in its' tracks by
starving it by eating NO sugar/carbohydrates, just protein and fat, the good ones of course.
Remember, there is NO known disease from a deficiency of any carbohydrate. BUT, there
are lots for protein deficiencies and also for fat.

Here is the article on Sugar and Cancer.
http://www.lowcarbluxury.com/newsle...3-no04-pg2.html
There seems to be no disagreement that (most) cancer cells cannot use
triglycerides for energy but must use glucose. They also don't need oxygen
since the usage of glucose can be anaerobic, again there seems to be no
disagreement on that fact.

Here is search parameters for PubMed.
anaerobic[Text Word] AND glycolysis[Text Word] AND cancer[Text Word]

A review of cancer cachexia and abnormal glucose metabolism in humans with cancer.
http://www.ncbi.nlm.nih.gov/entrez/...st_uids=1506607

Fatty acid synthase: a metabolic oncogene in prostate cancer?
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=14689581

I was somewhat confused by the seemingly dual role of glycolysis as both aerobic
(uses oxygen) and anaerobic. But I have finally understood why both paths exist.
The aerobic is the preferred path and is used for "normal" metabolism. BUT, when
you intensely use a muscle, as in when you are running for you LIFE!, then you
just CANNOT get enough oxygen to the muscle. So to keep you alive, the muscle
switches over to the anaerobic path so you can have energy to keep running and
not become dinner. I have included aerobic in the search, since these references
also use as fact the conclusion that cancer cells use large amounts of glucose.

aerobic[Text Word] AND glycolysis[Text Word] AND cancer[Text Word]

Why do cancers have high aerobic glycolysis?
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15516961
http://www.nature.com/cgi-taf/DynaP...s=doi1110228193

Hydrodynamic consequences of glycolysis: thermodynamic basis and clinical relevance.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15467425

Akt stimulates aerobic glycolysis in cancer cells.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15172999
QUOTE from Abstract!! "Akt-expressing cells were more susceptible than control
cells to death after glucose withdrawal."

Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=11943784

Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=12659686

Contribution by different fuels and metabolic pathways to the total ATP turnover of proliferating MCF-7 breast cancer cells.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=11988105
Interesting, seems to run counter to the others. But also it is looking at
aerobic not anaerobic glycolysis. ????

And here is another article from the same group.
Cancer metabolism: facts, fantasy, and fiction.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=14697210

***Related Articles (to Cancer metabolism: facts, fantasy, and fiction.)
AND cancer[Text Word]*** search below

Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=12659686

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo (13)C MRS.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=12217878
http://ajpendo.physiology.org/cgi/c...full/283/4/E623

The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=12873971
http://cancerres.aacrjournals.org/c...full/63/14/3847
Quote "Malignant cells characteristically exhibit altered metabolic patterns when compared with normal mammalian cells with increased reliance on anaerobic metabolism of glucose to lactic acid even in the presence of abundant oxygen.
The inefficiency of the anaerobic pathway is compensated by increased glucose flux, a phenomenon first noted by Otto Warburg ~80 years ago..."


Below are some of the journal articles that link copper to cancer.
Put the following in to the search box.
angiogenesis[Text Word] AND cancer[Text Word] AND copper[Text Word]

Angiogenesis and Cancer Control: From Concept to Therapeutic Trial
by Steven Brem, MD
http://www.moffitt.usf.edu/pubs/ccj/v6n5/article2.htm

Role of copper in tumour angiogenesis--clinical implications.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15487757

Copper deficiency as an anti-cancer strategy.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15163301
Zinc is also a copper chelator, so tetrathiomolybdate does not have to be
used - of course then the drug companies do not make any money, just the
vitamin/mineral/supplment companies do. Smile

A requirement for copper in angiogenesis.
http://www.ncbi.nlm.nih.gov/entrez/...t_uids=15080367