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Maté: a risk factor for oral and oropharyngeal cancer. Goldenberg D. Oral Oncol. 2002 Oct;38(7):646-9. Review. PMID: 12167417

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Michelakis ED, Webster L, Mackey JR. Br J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review. PMID: 18766181 doi:10.1038/sj.bjc.6604554 The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials More than 40 nonrandomised trials of DCA in small cohorts of patients have been reported, but the first two randomised control trials of chronic oral therapy with DCA in congenital mitochondrial diseases were reported in 2006. In the first, a blinded placebo-controlled study was performed with oral DCA administered at 25 mg kg-1 day-1 in 30 patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (Kaufmann et al, 2006). Most patients enrolled in the DCA arm developed symptomatic peripheral neuropathy, compared with 4 out of 15 in the placebo arm, leading to the termination of the study. Seventeen out of 19 patients had at least partial resolution of peripheral neurological symptoms by 9 months after discontinuation of DCA. This neurotoxicity res

Dietary vitamin D and cancers of the oral cavity and esophagus. Lipworth L, Rossi M, McLaughlin JK, Negri E, Talamini R, Levi F, Franceschi S, La Vecchia C. Ann Oncol. 2009 Sep;20(9):1576-81. Epub 2009 Jun 1. PMID: 19487490 Conclusion: We observed inverse associations between dietary vitamin D intake and risk of SCCE and, perhaps, oral/pharyngeal cancer, which were most pronounced among heavy current smokers and heavy consumers of alcohol.

Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity. Lachenmeier DW. J Occup Med Toxicol. 2008 Nov 13;3:26. PMID: 19014531 doi:10.1186/1745-6673-3-26

Grant WB, Garland CF, Gorham ED. An estimate of cancer mortality rate reductions in Europe and the US with 1,000 IU of oral vitamin D per day. Recent Results Cancer Res. 2007;174:225-34. PMID: 17302200 [PubMed - in process]

An estimate of cancer mortality rate reductions in Europe and the US with 1,000 IU of oral vitamin D per day. Grant WB, Garland CF, Gorham ED. Recent Results Cancer Res. 2007;174:225-34. Review. PMID: 17302200

Development of HPV vaccines for HPV-associated head and neck squamous cell carcinoma. Devaraj K, Gillison ML, Wu TC. Crit Rev Oral Biol Med. 2003;14(5):345-62. Review. PMID: 14530303

Benefits of Vitamin D Supplementation Joel M. Kauffman, Ph.D. Journal of American Physicians and Surgeons Volume 14 Number 2 - Summer 2009 Clinical trials show that vitamin D supplementation at higher levels than previously recommended is beneficial for many conditions. It decreases the frequency of falls and fractures, helps prevent cardiovascular disease, and reduces symptoms of colds or influenza. Benefits are also seen in diabetes mellitus, multiple sclerosis, Crohn disease, pain, depression, and possibly autism. Sunlight does not cause an overdose of vitamin D production, and toxicity from supplementation is rare. Dose recommendations are increasing, but appear to be lagging the favorable trial results. A number of common drugs deplete vitamin D levels, and others may limit its biosynthesis from sunlight. People with adequate levels from sun exposure will not benefit from supplementation. While dietary intake is helpful, supplementation is better able to raise serum 25-hydroxyvitamin D , the major circulating metabolite, to the level now thought adequate, 30-50 ng/mL. Where there is inadequate daily sun exposure, oral doses of 1,000-2,000 IU/d are now considered routine, with much higher doses (up to 50,000 IU) for rapid repletion now considered safe.

Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer. Lönnroth C, Andersson M, Arvidsson A, Nordgren S, Brevinge H, Lagerstedt K, Lundholm K. Cancer Immun. 2008 Feb 29;8:5. PMID: 18307280 MHC II protein (HLA-DP, -DQ, -DR) levels and infiltration by CD4+ T-helper cells of tumor stroma increased upon NSAID treatment, while CD8+ cytotoxic T-lymphocytes increased in both tumor stroma and epithelium. Molecules associated with immunosuppressive T regulatory cells (FOXP3, IL-10) were significantly decreased in indomethacin-exposed tumors. Standard oral administration of NSAID three days preoperatively was enough to increase tumor infiltration by seemingly activated immune cells. These findings agree with previous information that high pr

Beta glucan is a scientifically proven biological defense modifier (BDM) that nutritionally potentiates and modulates the immune response. As a supplement, after swallowing orally, Beta glucan is ingested primarily through macrophage and dendritic immune cells, to nutritionally and safely yield, through immune response potentiation and modulation, in many instances various therapeutic healing effects generated by the immune cells.  For many years Glucans have been investigated (History) for these immune enhancing properties, particularly their ability to activate macrophage immune cells and NK-Cells, plus in turn, the T-Cells, and B-Cells including selected cytokines and complement. 

Derived from the bulb or clove of the plant. Garlic is used as a spice and to treat hyperlipidemia, hypertension, atherosclerosis, cancer, and infections. Processing can have a substantial effect on the chemical content in garlic; the volatile oil components are sensitive to heat and certain enzymes are acid-labile. Several oral garlic formulations are available, and clinical studies have addressed a variety of the proposed claims. Placebo-controlled trials on the cholesterol lowering effect of garlic yielded mixed results (16) (17) (18) (21) (22) (26). Studies evaluating the antithrombotic effects repeatedly have shown modest reduction in platelet aggregation, but varying levels of fibrinolytic activity. Research shows mixed effects with regard to reductions in blood glucose, blood pressure, or risk of cardiovascular disease (23). Frequently reported adverse events include bad breath, headache, fatigue, GI upset, diarrhea, sweating, and possible hypoglycemia (9). Because garlic is known to decrease platelet aggregation and potentially elevate the INR, it should not be used with anticoagulants or in patients with platelet dysfunction (15). Garlic appears to induce cytochrome p450 3A4 and may enhance metabolism of many medications (e.g. cyclosporin and saquinavir) (12). An analysis of several case-control studies in Europe suggests an inverse association between garlic consumption and risk of common cancers (25).

Not enough vitamin D: health consequences for Canadians. Schwalfenberg G. Can Fam Physician. 2007 May;53(5):841-54. Review PMID: 17872747 Conclusion Low levels of VTD are considered a major public health problem in Canada, especially during the winter. Those with risk factors should be screened for low 25(OH)D levels and repletion therapy instituted if needed. Researchers have estimated that the oral dose of vitamin D3 to attain and maintain 25(OH)D levels >80 nmol/L is 2200 IU/d if baseline levels are 20 to 40 nmol/L, 1800 IU/d if levels are 40 to 60 nmol/L, and 1160 IU/d if levels are between 60 and 80 nmol/L.64 We need to ensure that patients have healthy blood levels of 25(OH)D to prevent levels of parathyroid hormone from rising and to maximize absorption of calcium, magnesium, and phosphate. Positive effects on bone are marginal at best unless patients consume at least 800 IU/d of VTD. The emerging and exciting role of the VTD receptor and the actions of VTD in maintaining health in other cell types have become more apparent during the last decade.

Simultaneously Blocking Glycolysis and Fat Metabolism Can the use of DCA and a fatty acid metabolism blocker together force more cancer cells into using aerobic metabolism? Tim McGough used green tea extract, which contains EGCG, in his fantastic response. DCA works by reactivating mitochondria and shifts metabolism from glycolysis to glucose oxidation. Hopefully the cancer cell will then undergo apoptosis. However, cancer cells have an alternate energy source: fat metabolism. This page explores to possibility of blocking fat metabolism to help force the cell into apoptosis. Oral squamous cell carcinoma is a cancer that does not respond well to DCA. This study, Head and Neck Cancer Cell Lines Are Resistant to Mitochondrial-Depolarization-Induced Apoptosis states: "Results: ΔΨm in head and neck cell lines started to show slight loss of ΔΨm, while HL-60 showed significant loss of ΔΨm after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. Conclusions: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane-depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.(head and neck squamous cell carcinoma)" Note that although the cell lines were depolarized, apoptosis did not occur. So I checked to see if fatty acid metabolism is used by squamous cell carcinoma.

For five gruelling months in 2006 and 2007, Carol Kanga suffered through treatment for a life-threatening case of throat cancer linked to an unlikely source: a sexually transmitted viral infection. Kanga's treatment was successful, but the virus that struck her is causing increasing concern among some researchers who think it is causing a small-scale epidemic of throat cancer. That virus, scientists have proved only in the last two years, is human papillomavirus, or HPV - the same virus that's behind most cases of cervical cancer.

ScienceDaily (Apr. 10, 2009) - New research from Trinity College Dublin published in this month's Annals of Surgery points to a potentially significant advance in the treatment of patients undergoing major cancer surgery. The study was carried out by the oesophageal research group at Trinity College Dublin and St James's Hospital. A randomised controlled trial showed omega-3 fatty acids given as part of an oral nutritional supplement resulted in the preservation of muscle mass in patients undergoing surgery for oesopahageal cancer, a procedure normally associated with significant weight loss and quality of life issues.

Phase I Study of White Button Mushroom Extract in Preventing the Recurrence of Breast Cancer in Postmenopausal Women Who Are Breast Cancer Survivors. This is a dose-escalation study. Patients receive oral white button mushroom extract twice daily for 12 weeks in the absence of a second primary ductal carcinoma in situ, invasive breast cancer, or unacceptable toxicity.ble toxicity.\n

Factors associated with clinical benefit from epidermal growth factor receptor inhibitors in recurrent and metastatic squamous cell carcinoma of the head and neck. Cohen EE, Halpern AB, Kasza K, Kocherginsky M, Williams R, Vokes EE. Oral Oncol. 2009 Oct;45(10):e155-60. Epub 2009 Jul 7. PMID: 19586795

Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator. Pereira CV, Machado NG, Oliveira PJ. Toxicol Sci. 2008 Oct;105(2):408-17. Epub 2008 Jul 3. PMID: 18599498 doi: 10.1124/jpet.107.128017 The data from the present work appear to show that berberine also presents some degree of toxicity to "nontumor" systems, which should be carefully understood. ANT inhibition in nontumor cells by berberine would be responsible for a decrease in energy production and could also result in MPT induction. To the best of our knowledge, no full toxicity assessment exists for berberine in humans, although its use in several commercially available supplements suggests that the compound may present a relatively wide safety interval. In fact, a study with patients with congestive heart failure treated with 1.2 g/day of oral berberine revealed low toxicity and resulted into an average plasma concentration of 0.11 mg/l which would translate into 0.3µM (Zeng and Zeng, 1999Go). Repeated cumulative treatments, alternative forms of formulation (e.g., topical application vs. injection) or more importantly, active mitochondrial accumulation due to its positive charge would be expected to increase its concentration in cells into the range of concentrations used in this study. Empirical data from nontraditional medicines plus the use of extensive clinical assays would allow the use of berberine as a promising antimelanoma agent while maintaining its safety for humans. In radial/vertical forms of melanoma, a possible topical application of berberine would also be possible, thus minimizing side effects on other organs. In conclusion, the present work identifies the ANT as an important target for berberine, with clear relevance for its proposed antitumor effects.

"Berberine is a quaternary ammonium salt from the group of isoquinoline alkaloids. It is found in such plants as Berberis, goldenseal (Hydrastis canadensis), and Coptis chinensis, usually in the roots, rhizomes, stems, and bark. Berberine is strongly yellow colored, which is why in earlier times berberis species were used to dye wool, leather and wood. Wool is still today dyed with berberine in Northern India Berberine (BBR) is a natural compound with up-regulating activity on both low-density-lipoprotein receptor (LDLR) and insulin receptor (InsR). This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome.[12] Berberine has been tested and used successfully in experimental[13] and human diabetes mellitus.[14][15][16] Berberine has been shown to lower elevated blood glucose as effectively as metformin.[17] The mechanisms include inhibition of aldose reductase,[18] inducing glycolysis,[19] preventing insulin resistance[20] through increasing insulin receptor expression[14] and acting like incretins. Berberine has drawn extensive attention towards its antineoplastic effects.[43][44] It seems to suppress the growth of a wide variety of tumor cells including breast cancer,[45] leukemia, melanoma,[46] epidermoid carcinoma, hepatoma, oral carcinoma, tongue carcinoma,[47] glioblastoma, prostate carcinoma, gastric carcinoma.[48][49] Animal studies have shown that berberine can suppress chemical-induced carcinogenesis, tumor promotion, tumor invasion,[50][51][52][53][54] prostate cancer,[55][56][57][58] neuroblastoma,[59][60] and leukemia.[34][61] It is a radiosensitzer of tumor cells but not of normal cells

Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration.\nYeom CH, Jung GC, Song KJ.\nJ Korean Med Sci. 2007 Feb;22(1):7-11.\nPMID: 17297243