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"Ann Arbor, MI - New laboratory research suggests that the COX-2 inhibitor celecoxib (Celebrex, Pfizer), might impede the action of "baby" aspirin [1]. Dr Gilad Rimon (University of Michigan, Ann Arbor) and colleagues found evidence that this was the case in a dog model and say that "it will be important to determine" whether the same is true in humans. The report was published online December 1, 2009 in the Proceedings of the National Academy of Medicine. Celecoxib is the only COX-2 inhibitor to have remained on the market in the US, and doctors who recommend this painkiller often coprescribe a daily low dose of 81 mg of aspirin (known as a "baby" dose) to counteract any possible prothrombotic effects of the coxib, while minimizing potential gastrointestinal toxicity of the aspirin. Senior author of the new work, Dr William L Smith (University of Michigan, Ann Arbor), explained to heartwire that previous studies in humans have shown that celecoxib does not interfere with the effect of a standard dose of aspirin (325 mg), but any potential interaction of celecoxib with the lower dose has not been examined. Stagger dosing to avoid any potential problems First, Smith explained that he and his colleagues looked in vitro at celecoxib and found that it binds to one of two available sites on the COX-1 enzyme. "This surprised us," he commented. "It appears to interfere with the ability of some other drugs to affect COX-1, most notably aspirin." Second, in beagles, they administered the dog-equivalent of a baby dose of aspirin in humans and then gave some of the animals the equivalent of 100 mg of celecoxib twice daily in addition. "Celecoxib plus aspirin interfered with the normal effect of low-dose aspirin on platelets," he notes. Smith says this observation obviously requires confirmation in humans, but in the meantime he suggests "getting around the problem" by patients taking the low-dose aspirin at least 15 to 30 minutes before the celecoxib is taken, "because

I stumbled on one of the growing number of local media stories on the power of vitamin D. \nIn one story, a purported "expert" was talking about the benefits of "high-dose" vitamin D, meaning up to 1000, even 2000 units per day. \nI regard this as high-dose---for an infant. \nJudging by my experiences, now numbering well over 1000 patients over three years time, I'd regard this dose range not as "high dose," nor moderate dose, perhaps not even low dose. I'd regard it as barely adequate.

The Toronto group gave a fixed low dose (2,000 units) of the prehormone, cholecalciferol, a very safe compound that never causes high calcium in the doses used. In fact, the lowest dose of cholecalciferol known to cause high blood calcium is more than 20,000 units. Therefore, the Toronto group got better results with one-tenth the comparable dose of deltanoids! Vieth wanted to use more cholecalciferol but widespread ignorance about the physiology and pharmacology of vitamin D remains and he could not get adequate dosing past the various review committees.

Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. Koitaya N, Ezaki J, Nishimuta M, Yamauchi J, Hashizume E, Morishita K, Miyachi M, Sasaki S, Ishimi Y. J Nutr Sci Vitaminol (Tokyo). 2009 Feb;55(1):15-21. PMID: 19352059 It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Saw CL, Huang Y, Kong AN. Biochem Pharmacol. 2010 Feb 1;79(3):421-30. Epub 2009 Sep 8. PMID: 19744468

"THURSDAY, Dec. 17 (HealthDay News) -- In a surprise finding, Canadian researchers report that the immediate effect of the fish oil fatty acids that are good for the heart is a short-term increase in blood fats and the molecules that help them form clots. "We were surprised to find that the acute response has some potentially negative effects in comparison to what you might expect from chronic, long-term intake," said Lindsay E. Robinson, an associate professor of nutrition at the University of Guelph, and leader of the group reporting the finding in the January issue of the Journal of Nutrition. However, the study results shouldn't affect the current recommendation for eating more oily fish to get the omega-3 polyunsaturated acids that reduce the risk of blood clots that can cause heart attacks and stroke, Robinson said. "The recommendation to increase intake is very well-studied, and this doesn't change it," she said. And the effects were seen in a selected group of middle-aged men with metabolic syndrome, a combination of high blood pressure, obesity and elevated blood fat levels, Robinson noted. In the study, eight men had controlled intake of three regimens: high doses of omega-3 fatty acids, low doses of them and just plain water. Robinson and her colleagues measured several blood components involved in clotting, including fats and clotting factors such as plasminogen-activator inhibitor-1 (PAI-1) for the following eight hours. PAI-1 inhibits the destruction of blood clots, so high levels of it in the blood increase the risk of artery-blocking clots. The researchers found that both omega-3 fatty acid regimens increased blood fat and clotting factor activity. But the increase in clotting factor was greater for the higher doses of omega-3 fatty acids than for the lower intakes. Robinson said her group hopes to do further studies of the immediate effects of omega-3 fatty acid intake. "We need to look at the mechanisms, why blood lipid levels go up," she

Venn BJ, Green TJ, Moser R, Mann JI. Related Articles, Links Free Full Text Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study. Am J Clin Nut

Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nogusa S, Gerbino J, Ritz BW. Nutr Res. 2009 Feb;29(2):139-43. PMID: 19285605 doi:10.1016/j.nutres.2009.01.005

"Possible effects of berberine, a chemical found in small amounts in goldenseal, include headache, slow heart rate, nausea, vomiting, abdominal bloating, and low white blood cell count. It is not clear if the amount of berberine in goldenseal products is enough to cause these reactions. Toxic doses of berberine may cause seizures or irritation of the esophagus and stomach when taken by mouth. Berberine used intravenously (through the veins) may cause abnormal heart rhythms. Based on laboratory and animal studies, berberine may increase blood concentrations of bilirubin. Berberine theoretically may cause low blood pressure, although a different chemical in goldenseal, hydrastine, may actually cause increased blood pressure. There is limited study of the blood pressure effects of these agents in humans. Based on laboratory and animal studies, the use of goldenseal or berberine could increase the risk of bleeding. However, there are no reliable published reports of bleeding in humans. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. Based on an initial report, goldenseal or berberine may cause increased sun sensitivity, although this is not a commonly reported symptom. Based on laboratory studies, berberine may lower blood sugar. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary. "

Ketogenic diets and physical performance. Phinney SD. Nutr Metab (Lond). 2004 Aug 17;1(1):2. PMID: 15507148 doi:10.1186/1743-7075-1-2 Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15-25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis. Both observational and prospectively designed studies support the conclusion that submaximal endurance performance can be sustained despite the virtual exclusion of carbohydrate from the human diet. Clearly this result does not automatically follow the casual implementation of dietary carbohydrate restriction, however, as careful attention to time for keto-adaptation, mineral nutriture, and constraint of the daily protein dose is required. Contradictory results in the scientific literature can be explained by the lack of attention to these lessons learned (and for the most part now forgotten) by the cultures that traditionally lived by hunting. Therapeutic use of ketogenic diets should not require constraint of most forms of physical labor or recreational activity, with the one caveat that anaerobic (ie, weight lifting or sprint) performance is limited by the low muscle glycogen levels induced by a ketogenic diet, and this would strongly discourage its use under most conditions of competitive athletics.

"ScienceDaily (Oct. 8, 2009) - Women with breast cancer should be given high doses of vitamin D because a majority of them are likely to have low levels of vitamin D, which could contribute to decreased bone mass and greater risk of fractures, according to scientists at the University of Rochester Medical Center." Scientists funded by the NCI analyzed vitamin D levels in each woman, and the average level was 27 nanograms per milliliter; more than two-thirds of the women had vitamin deficiency. Weekly supplementation with high doses of vitamin D -- 50,000 international units or more -- improved the levels, according to Peppone's study. The U.S. Institute of Medicine suggests that blood levels nearing 32 nanograms per milliliter are adequate.

A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

"NOTTINGHAM, England, Dec. 29 (UPI) -- A drug derived from a mushroom -- cordycepin -- may be used to treat some cancers, British researchers say. Dr. Cornelia de Moor of The University of Nottingham in England and colleagues are investigating the drug originally extracted from a rare parasitic mushroom called cordyceps that grows on caterpillars. The researchers say low-dose cordycepin seems to inhibit the uncontrolled growth and division of cells and at high doses it also inhibits growth by stopping cells from sticking together. Both of these effects, they say, probably have the same underlying mechanism -- interfering with the production of cell proteins.

Should new vitamin D recommendations be made? According to a new study carried out at the University of California at Davis, the recommended dose of vitamin D that most experts recommend taking is too low during the winter months when there's less direct sunlight

Side Effects and Warnings Berberine has been reported to cause nausea, vomiting, hypertension (high blood pressure), respiratory failure and paresthesias (abnormal sensations such as numbness or tingling); however, clinical evidence of such adverse effects is not prominent in the literature. Rare adverse effects including headache, skin irritation, facial flushing, headache, bradycardia (slowed heart rate) have also been reported with the use of berberine. Use cautiously when taking berberine for longer than eight weeks due to theoretical changes in bacterial gut flora. Use cautiously in individuals with diabetes, as both human and animal studies indicate that berberine may decrease blood sugar levels. Also use cautiously in individuals with hypotension (low blood pressure), as berberine may have antihypertensive effects. Patients with cardiovascular disease should also use caution as berberine has been associated with the development of ventricular arrhythmias in subjects with congestive heart failure. Although not well studied in humans, berberine may also theoretically cause delays in small intestinal transit time or increase the risk of bleeding. Berberine may cause abortion, eye or kidney irritation, nephritis (inflamed kidneys), dyspnea (difficulty breathing), flu-like symptoms, giddiness, lethargy, or liver toxicity. Patients with leukopenia (abnormally low white blood cell count) should use cautiously due to the potential for development of leukopenia symptoms. When injected under the skin, berberine may cause hyperpigmentation in the arm. Use berberine cautiously in individuals with high exposure to sunlight or artificial light due to potential for adverse phototoxic reactions. Avoid in newborns due to potential for increase in free bilirubin, jaundice, and development of kernicterus (brain damage caused by severe newborn jaundice). Use berberine cautiously in children due to a lack of safety information. Pregnancy and Breastfeeding Berberine is not recomme

Jenkins DJ, Kendall CW, Marchie A, Parker TL, Connelly PW, Qian W, Haight JS, Faulkner D, Vidgen E, Lapsley KG, Spiller GA. Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a),

Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. Koitaya N, Ezaki J, Nishimuta M, Yamauchi J, Hashizume E, Morishita K, Miyachi M, Sasaki S, Ishimi Y. J Nutr Sci Vitaminol (Tokyo). 2009 Feb;55(1):15-21. PMID: 19352059 These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

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

"Nov 14, 2005 | Michael O'Riordan. Dallas, TX - The addition of eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduced the incidence of major coronary events, largely driven by a reduction in unstable angina, when compared with patients taking statins alone. A subgroup analysis of the study, which involved a large number of primary-prevention patients, revealed that statin-treated secondary-prevention patients gained the most benefit from fish-oil supplementation. Dr Mitsuhiro Yokoyama Presenting the results of the Japan EPA Lipid Intervention Study (JELIS) during the late-breaking clinical-trials session at the American Heart Association Scientific Sessions 2005, Dr Mitsuhiro Yokoyama (Kobe University Graduate School of Medicine, Japan) said that the mechanism of benefit with EPA, a seafood-based, long-chain, n-3 polyunsaturated fatty acid, appears to be unrelated to the effects of cholesterol lowering. Commenting on the results of the study for heartwire, Dr Lawrence Appel (Johns Hopkins University School of Medicine, Baltimore, MD) said the findings are impressive given that the benefit of fish oil was observed on top of a regimen of statin therapy. He added that there are still some unknowns about which patient population would benefit most from fish oil."

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.