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"As far as I can tell, MK-4 is capable of performing all the functions of vitamin K. MK-4 can even activate blood clotting factors, which is a role traditionally ascribed to vitamin K1. Babies are often born clotting deficient, which is why we give newborns vitamin K1 injections in the U.S. to prevent hemorrhaging. In Japan, they give children MK-4 to prevent hemorrhage, an intervention that is very effective. Could that have to do with the fact that Japan has half the infant mortality rate of the U.S.? Today, I found another difference between MK-4 and MK-7. I was reading a paper about SXR-independent effects of vitamin K2 on gene expression. The investigators found that MK-4 strongly activates transcription of two specific genes in osteoblast cells. Osteoblasts are cells that create bone tissue. The genes are GDF15 and STC2 and they're involved in bone and cartilage formation. They tested K1 and MK-7, and in contrast to MK-4, they did not activate transcription of the genes in the slightest. This shows that MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have. That being said, MK-7 may still have a place in a healthy diet. Just because it can't do everything MK-4 can, doesn't mean it has no role. It may be able to fill in for MK-4 in some functions, or reduce the dietary need for MK-4. But no one really knows at this point. Hunter-gatherers would have had a source of longer menaquinones, including MK-7, from livers. So it's possible that we're adapted to a modest MK-7 intake on top of MK-4. "

Vitamin K content of foods and dietary vitamin K intake in Japanese young women. Kamao M, Suhara Y, Tsugawa N, Uwano M, Yamaguchi N, Uenishi K, Ishida H, Sasaki S, Okano T. J Nutr Sci Vitaminol (Tokyo). 2007 Dec;53(6):464-70. PMID: 18202532 Several reports indicate an important role for vitamin K in bone health as well as blood coagulation. However, the current Adequate Intakes (AI) might not be sufficient for the maintenance of bone health. To obtain a closer estimate of dietary intake of phylloquinone (PK) and menaquinones (MKs), PK, MK-4 and MK-7 contents in food samples (58 food items) were determined by an improved high-performance liquid chromatography method. Next, we assessed dietary vitamin K intake in young women living in eastern Japan using vitamin K contents measured here and the Standard Tables of Food Composition in Japan. PK was widely distributed in green vegetables and algae, and high amounts were found in spinach and broccoli (raw, 498 and 307 microg/100 g wet weight, respectively). Although MK-4 was widely distributed in animal products, overall MK-4 content was lower than PK. MK-7 was observed characteristically in fermented soybean products such as natto (939 microg/100 g). The mean total vitamin K intake of all subjects (using data from this study and Japanese food composition tables) was about 230 microg/d and 94% of participants met the AI of vitamin K for women aged 18-29 y in Japan, 60 microg/d. The contributions of PK, MK-4 and MK-7 to total vitamin K intake were 67.7, 7.3 and 24.9%, respectively. PK from vegetables and algae and MK-7 from pulses (including fermented soybean foods) were the major contributors to the total vitamin K intake of young women living in eastern Japan

Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats. Yamaguchi M, Taguchi H, Gao YH, Igarashi A, Tsukamoto Y. J Bone Miner Metab. 1999;17(1):23-9. PMID: 10084398 This study demonstrates that the intake of dietary MK-7 has a preventive effect on bone loss caused by OVX. This effect may be partly caused by MK-4, which is formed by degradation of MK-7.

"18 645 patients with a total cholesterol of 6·5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. Findings At mean follow-up of 4·6 years, we detected the primary endpoint in 262 (2·8%) patients in the EPA group and 324 (3·5%) in controls-a 19% relative reduction in major coronary events (p=0·011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4·7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8·7%] in the EPA group vs 197 [10·7%] in the control group; p=0·048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1·4%] in the EPA group vs 127 [1·7%] in the control group; p=0·132)."

Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7.\nSchurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C.\nBlood. 2007 Apr 15;109(8):3279-83. Epub 2006 Dec 7.\nPMID: 17158229 \nDOI 10.1182/blood-2006-08-040709\n

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A. Am J Cardiol. 2007 Apr 1;99(7):903-5. Epub 2007 Feb 8. PMID: 17398180 In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. The mechanism by which atorvastatin increases vitamin D levels is related to inhibition of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol is synthesized from 7-dehydrocholesterol, which is also a precursor of vitamin D3. For this reason, we initially observed a statistically significant relation between total cholesterol and vitamin D. HMG-CoA enzyme reductase is key to the synthesis of cholesterol, whereas ultraviolet radiation causes the formation of 25-hydroxyvitamin D. Inhibition of the enzyme may increase levels of 7-dehydrocholesterol and increase the synthesis of 25-hydroxycholecalciferol, thereby increasing vitamin D levels,10 although we observed no relation between lower cholesterol and increased vitamin D. In addition, 25-hydroxyvitamin D has been shown to inhibit HMG-CoA enzyme reductase activity in in vitro studies.11 A greater concentration of vitamin D could increase enzymatic inhibition, acting in synergy with the statin in decreasing total cholesterol.

Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase 2 trial. Barrera JL, Verastegui E, Meneses A, Zinser J, de la Garza J, Hadden JW. Arch Otolaryngol Head Neck Surg. 2000 Mar;126(3):345-51. PMID: 10722007 The natural cytokine mixture is a collection of natural human cytokines induced from human peripheral blood mononuclear cells. It contains IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, interferon gamma, tumor necrosis factor , and granulocyte-macrophage and granulocyte colony-stimulating factor in nanogram quantities. It lacks IL-3, IL-4, IL-5, and IL-7. [...] This IRX-2 strategy uses perilymphatic local administration along with contrasuppression with low-dose cyclophosphamide and indomethacin and with zinc replacement therapy (as an immunorestorative). The data presented herein demonstrate that H&N SCC can respond very well to immunotherapy: there was a response rate of 100% in this series of 15 patients, with clinical reduction in tumor (1 complete response, 7 partial responses, and 7 minor responses) and histological evidence of tumor regression of 42%. Overall, the average combined estimated tumor reduction exceeded 70%. Also, patients with oral cancer noted marked analgesic and hemostatic effects from this therapy, with healing of oral lesions. [...] It is important to note that adjuvant chemotherapy is not used at INCAN. Many studies23 indicate that treatment with fluorouracil and cisplatin, the combination most in use, is effective for reducing tumors in the majority of patients; however, with no meaningful impact on survival, their routine use in the United States has recently been questioned.24-25 The expense, toxic effects, and lack of effectiveness of both drugs has made their use in other less affluent countries unwarranted. The current data on the use of IRX-2 in this and other protocols8-10 hint at improved survival, and a phase 3 randomized controlled study comparing this protocol with chemotherapy arm is to be initiat

Copper Control as an Antiangiogenic Anticancer Therapy: Lessons from Treating Wilson's Disease -- Brewer 226 (7): 665 -- Experimental Biology and Medicine

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Cardiovasc Diabetol. 2009 Feb 3;8:7. PMID: 19187564 doi:10.1186/1475-2840-8-7 CONCLUSION: The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.

Holick, M. F., MacLaughlin, J. A. & Doppelt, S. H. (1981) Factors that influence the cutaneous photosynthesis of previtamin D3. Science 211:590-593 When human skin was exposed to simulated solar ultraviolet radiation, epidermal 7-dehydrocholesterol was converted to previtamin D3. During prolonged exposure to simulated solar ultraviolet radiation, the synthesis of previtamin D3 reached a plateau at about 10 to 15 percent of the original 7-dehydrocholesterol content, and previtamin D3 was photoisomerized to two biologically inert isomers, lumisterol3 and tachysterol3. Increases either in skin melanin concentration or in latitude necessitated increases in the exposure time to simulated solar ultraviolet radiation required to maximize the formation, but not the total content, of previtamin D3. In order of importance, the significant determinants limiting the cutaneous production of previtamin D3 are (i) photochemical regulation, (ii) pigmentation, and (iii) latitude.

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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

Mechanisms underlying the biphasic effect of vitamin K1 (phylloquinone) on arterial blood pressure.\nTirapelli CR, Resstel LB, de Oliveira AM, Corrêa FM.\nJ Pharm Pharmacol. 2008 Jul;60(7):889-93.\nPMID: 18549675 \nDOI: 10.1211/jpp.60.7.0010\n

The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gómez AL, Scheett TP, Volek JS. J Nutr. 2002 Jul;132(7):1879-85. PMID: 12097663

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Mente A, de Koning L, Shannon HS, Anand SS. Arch Intern Med. 2009 Apr 13;169(7):659-69. PMID: 19364995

A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls - a cross-sectional study. Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. Br J Nutr. 2006 Jul;96(1):124-30. PMID: 16870000 Seasonal variation in S-25-OHD and bone remodelling markers accompanied by negative correlation between S-25-OHD and S-iPTH was seen in this cross-sectional study of adolescent girls. In addition, the seasonal rhythm contributed 7.0-7.6 % difference in the BMD of lumbar vertebrae and left femur in early puberty girls. This variation should be avoided since it could hamper peak bone mass attainment.

Conclusion: Vitamin D3 at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels. Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children. Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, El-Hajj Fuleihan G. J Clin Endocrinol Metab. 2008 Jul;93(7):2693-701. Epub 2008 Apr 29. PMID: 18445674 doi:10.1210/jc.2007-2530