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Vitamin D-induced up-regulation of tumour necrosis factor alpha (TNF-alpha) in prostate cancer cells. Golovko O, Nazarova N, Tuohimaa P. Life Sci. 2005 Jun 17;77(5):562-77. Epub 2005 Feb 25. PMID: 15904673 doi:10.1016/j.lfs.2004.10.072 Combined addition of human recombinant TNF-alpha with calcitriol or CB1093 cause enhanced effect in induction of apoptosis. We conclude that under physiological conditions vitamin D activates only the transcription of TNF-alpha gene, for TNF-alpha protein synthesis additional cofactors are required. Therefore a cooperation of vitamin D and TNF-alpha may play an important role in the control of cell growth in prostate cancer.

A German group has now shown that the important inflammatory marker, tumor necrosis factor (TNF), is also reduced by vitamin D supplementation. Many studies have implicated increased TNF levels in promoting cancer. In this study, a modest vitamin D dose of 3320 units (83 micrograms) was given vs. placebo. The 25-hydroxy D level reached in the treated group was 34.2 ng/ml (85.5 nmol/L), which resulted in a 26.5% reduction in TNF compared with 18.7% reduction (?) in the placebo group.

Frick KK, LaPlante K, Bushinsky DA. RANK ligand and TNF-alpha mediate acid-induced bone calcium efflux in vitro. Am J Physiol Renal Physiol. 2005 Nov;289(5):F1005-11. Epub 2005 Jun 21. PMID: 15972386 [PubMed - indexed for MEDLINE

A plethora of research documents the role of chronic inflammatory mediators such as 5-lipooxygenase (5-LOX) and tumor necrosis factor-alpha (TNF-α) in the manifestation and progression of prostate and other cancers.7-19,30,31,33,49,52-54,87,88 The typical American diet is high in omega-6 fatty acids, saturated fats, and arachidonic acid. Over-consumption of these foods, and under-consumption of omega-3 fatty acids, contribute significantly to systemic chronic inflammatory states. Boswellia extracts have been thoroughly studied as natural remedies for inflammatory disorders. A patented extract from boswellia called 5-LOXIN® has potent ability to inhibit the enzyme 5-LOX, preventing the formation of protein-degrading enzymes, and protecting against inflammation-induced events that can promote tumor angiogenesis.

Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. Peterson CA, Heffernan ME. J Inflamm (Lond). 2008 Jul 24;5:10. PMID: 18652680 doi:10.1186/1476-9255-5-10 Conclusion Serum 25(OH)D status is inversely related to TNF-α concentrations in healthy women, which may in part explain this vitamin's role in the prevention and treatment of inflammatory diseases. Results gleaned from this investigation also support the need to re-examine the biological basis for determining optimal vitamin D status.

"Let's shine some sunlight on these knowledge deficiencies: * Serum vitamin D levels have been dropping (as chronic inflammation has been increasing) over the last three decades -- has something changed in our diets? * Vitamin D deficiencies occur globally (not restricted to Northern latitudes or winter) -- related to diet? * Women are more vulnerable, because of cultural modesty in some countries, but males are still D-deficient. * A subset of people exposed to ample sunshine are still D-deficient. * Vitamin D deficient individuals also have elevated TNF. * Vitamin D deficiency and inflammation are risk factors in the same diseases. It seems that the simplest conclusion is that chronic inflammation leads to vitamin D deficiency, even though vitamin D deficiency may also contribute to inflammation."

The effects of whole mushrooms during inflammation. Yu S, Weaver V, Martin K, Cantorna MT. BMC Immunol. 2009 Feb 20;10:12. PMID: 19232107 doi:10.1186/1471-2172-10-12 In RAW 264.7 cells the induction of TNF-α production was highest in LPS and WB stimulated rather than the crimini, maitake, oyster, or shitake stimulated cells. The differences might be a result of differences in the quantity of the immunomodulatory substance or substances and or differences in solubility of mushrooms in the DMSO used to produce the extracts. However, the direction of the changes (increase versus decrease) were not different among the mushroom treatments. The lack of differential effects on cytokine secretion by the mushroom extracts suggests that the whole mushrooms must share a common component(s) that act to regulate immune function.

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Gogos CA, Ginopoulos P, Salsa B, Apostolidou E, Zoumbos NC, Kalfarentzos F. Cancer. 1998 Jan 15;82(2):395-402. PMID: 9445198 DOI: 10.1002/(SICI)1097-0142(19980115)82:23.0.CO;2-1 Dietary supplementation with omega-3 PUFA (18 g/day) restored both the Th/Ts cell ratio and TNF production by endotoxin-stimulated PBMC. Our finding is not in accordance with former reports that long term consumption of omega-3 PUFA decreases T cell mitogenic response, DTH, and the percentage of T-helper cells,[28] and this may be the result of the parallel antioxidant effect of vit E. Most significantly, omega-3 PUFA increased the survival of all our patients, ...

Active Hexose Correlated Compound (AHCC) is an alpha-glucan rich nutritional supplement produced from the mycelia of shiitake (Lentinula edodes) of the basidiomycete family of mushrooms, and should not be confused or used as a drug or medicine.[1][2] AHCC was originally designed to lower high-blood pressure. However, researchers at Tokyo University found AHCC's influence upon the innate immune system highly beneficial and published the results in 1992, though not in the commonly indexed scientific literature. In this study, researchers found that AHCC significantly increased natural killer (NK) cell activity in cancer patients, and also enhanced the effects of killer T-cells, and cytokines (interferon, IL-12, TNF-alpha

Derived from the cap and stem of the mushroom, Reishi mushroom is used as an immune stimulant by patients with HIV or cancer. The active constituents are thought to include both beta-glucan polysaccharides and triterpenes (1). Extracts of Reishi can stimulate macrophages and alter the levels of TNF and interleukins (2) (3) (4) (5). Reishi also inhibited platelet aggregation (11) (12) and improved lower urinary tract symptoms (LUTS) in men (9) (10). Studies done in rats have shown that Reishi extract may alleviate chemotherapy-induced nausea (13). In clinical studies, Reishi increased plasma antioxidant capacity (6) (7)and enhanced immune responses in advance-stage cancer patients (8).

American Academy of Sleep Medicine. "Inflammation May Be Link Between Extreme Sleep Durations And Poor Health." ScienceDaily 7 February 2009. 25 February 2009 .

Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006 Feb;83(2):456S-460S. Review. PMID: 16470012 [PubMed - indexed for MEDLINE]

According to a recent study in the Archives of Internal Medicine, 75 percent of Americans do not get enough Vitamin D. Researchers have found that the deficiency may negatively impact immune function and cardiovascular health and increase cancer risk. Now, a University of Missouri nutritional sciences researcher has found that vitamin D deficiency is associated with inflammation, a negative response of the immune system, in healthy women.

Fish oil and treatment of cancer cachexia. Giacosa A, Rondanelli M. Genes Nutr. 2008 Apr;3(1):25-8. PMID: 18850196

Why fish oils may not always be adequate treatments for depression or other inflammatory illnesses: docosahexaenoic acid, an omega-3 polyunsaturated fatty acid, induces a Th-1-like immune response. Maes M, Mihaylova I, Kubera M, Bosmans E. Neuro Endocrinol Lett. 2007 Dec;28(6):875-80. PMID: 18063921

K. L. Fritsche Are Omega-3 Fatty Acids Effective in Enhancing Tumoricidal Cell Activity? J. Nutr., December 1, 2005; 135(12): 2916S - 2917S.

Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment. Meydani SN, Lichtenstein AH, Cornwall S, Meydani M, Goldin BR, Rasmussen H, Dinarello CA, Schaefer EJ. J Clin Invest. 1993 Jul;92(1):105-13. PMID: 8325975 doi:10.1172/JCI116537 the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased

Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, Stehle P, Koertke H, Koerfer R. Am J Clin Nutr. 2009 May;89(5):1321-7. Epub 2009 Mar 25. PMID: 19321573

Strong correlations have been noted between cardiovascular diseases and low bone density / osteoporosis-connections so strong that the presence of one type of pathology is considered a likely predictor of the other. This potentially causal relationship has led to the hypothesis that these conditions share core mechanisms. Recent advances in our understanding of the complimentary roles played by vitamin D3 and vitamin K2 in vascular and bone health provide support for this hypothesis, along with insight into key metabolic dysfunctions underlying cardiovascular disease and osteoporosis. Part I of this review summarizes current research linking vitamin D deficiency to cardiovascular disease, the physiological mechanisms underlying vitamin D's cardiovascular effects, and leading vitamin D researchers' recommendations for significantly higher supplemental doses of the pro-hormone. Part II reviews the vitamin K connection to cardiovascular disease; the ways in which vitamin D and vitamin K pair up to prevent inflammation, vascular calcification and osteoporosis; and the necessity of providing vitamin K along with vitamin D to preclude adverse effects associated with hypervitaminosis D, which include vascular and other soft tissue calcification.

Modulation of inflammatory cytokines by omega-3 fatty acids. Kang JX, Weylandt KH. Subcell Biochem. 2008;49:133-43. Review. PMID: 18751910