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Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. Volvert ML, Seyen S, Piette M, Evrard B, Gangolf M, Plumier JC, Bettendorff L. BMC Pharmacol. 2008 Jun 12;8:10. PMID: 18549472 doi:10.1186/1471-2210-8-10 Conclusion Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties.

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.\nChen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR, Levine M.\nProc Natl Acad Sci U S A. 2007 May 22;104(21):8749-54. Epub 2007 May 14.\nPMID: 17502596 \n doi: 10.1073/pnas.0702854104\n

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9. Epub 2005 Sep 12. PMID: 16157892

Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Serhan CN, Chiang N. Br J Pharmacol. 2008 Mar;153 Suppl 1:S200-15. Epub 2007 Oct 29. Review. PMID: 17965751 doi:10.1038/sj.bjp.0707489

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11105-9. Epub 2008 Aug 4. PMID: 18678913 doi: 10.1073/pnas.0804226105

Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Serhan CN, Chiang N. Br J Pharmacol. 2008 Mar;153 Suppl 1:S200-15. Epub 2007 Oct 29. Review. PMID: 17965751 DOI: 10.1038/sj.bjp.0707489

Safety of vitamin D3 in adults with multiple sclerosis. Kimball SM, Ursell MR, O'Connor P, Vieth R. Am J Clin Nutr. 2007 Sep;86(3):645-51. PMID: 17823429 Conclusions: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.

Biologic/Organic/Pharmacologic Therapies: Coley Toxins Detailed Scientific Review

The combination effects index (CI) analysis confirmed the synergy of clioquinol and clofibrate on inhibiting cancer cell viability. Using inhibitors to block PPARalpha signaling diminished the synergistic cytotoxicity of clioquinol and DHA. These results provide pharmacological evidence that the synergistic anticancer action of clioquinol and DHA is mediated by PPARalpha signaling in human cancer cells. PPARalpha signaling mediates the synergistic cytotoxicity of clioquinol and docosahexaenoic acid in human cancer cells. Tuller ER, Brock AL, Yu H, Lou JR, Benbrook DM, Ding WQ. Biochem Pharmacol. 2009 May 1;77(9):1480-6. Epub 2009 Feb 13. PMID: 19426685

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.

A popular vitamin supplement is being advertised with claims that are demonstrably untrue, as revealed by research published in the open access journal BMC Pharmacology. Benfotiamine is a synthetic derivative of thiamine (vitamin B1). It is marketed heavily as a dietary supplement using a selection of unsubstantiated, 'not-quite-medical' claims that tend to characterize this field. A large part of this campaign has been built around the belief that benfotiamine is lipid-soluble and, therefore, more physiologically active. Scientific research led by Dr Lucien Bettendorff of the Center for Cellular and Molecular Neurobiology at the University of Liège, Belgium, has entirely disproved these claims.

Cyclooxygenase (COX) is an enzyme (EC 1.14.99.1) that is responsible for formation of important biological mediators called prostanoids (including prostaglandins, prostacyclin and thromboxane). Pharmacological inhibition of COX can provide relief from the

"THURSDAY, Dec. 3 (HealthDay News) -- New research points to the possibility of a genetic link between vitamin D and heart disease. People with high blood pressure who had a gene variant that reduces vitamin D activation in the body were found to be twice as likely as those without the variant to have congestive heart failure, the study found. The finding may lead to a way to identify people at increased risk for heart disease, according to Robert U. Simpson, an assistant professor of pharmacology at the University of Michigan Medical School and his research colleagues. They analyzed the genetic profiles of 617 people. One-third had hypertension, one-third had hypertension and congestive heart failure, and the remaining third served as healthy controls. The researchers found that a variant in the CYP27B1 gene was associated with congestive heart failure in people with hypertension. The study is in the November issue of Pharmacogenomics."

"Supplements of French maritime pine bark extract may improve the flow of blood in the tiny blood vessels of the retina, and enhance sight in diabetics with early stage eye problems, says a new study. Visual acuity, or the clearness of vision, was found to improve from 14/20 to 17/20 in people with early stage retina damage associated with diabetes (diabetic retinopathy) following daily supplements of the pine bark extract, Pycnogenol, for two months. Forty-six diabetics participated in the randomised controlled study with the findings published in the Journal of Ocular Pharmacology and Therapeutics. "Our study suggests that Pycnogenol taken in the early stages of retinopathy may enhance retinal blood circulation accompanied by a regression of oedema, which favourably improves vision of patients," said lead researcher Dr Robert Steigerwalt. "Pycnogenol may be particularly beneficial for preventing this complication in diabetic patients, based on the large number of individuals who were diagnosed when the disease had already significantly progressed"

Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Kulkami SK et al. Phytotherapy Research, Published Online: 8 Dec 2009 This review attempts to discuss the pharmacological basis of the use of berberine in various central nervous system and related disorders. Its protective effect in Alzheimer's, cerebral ischemia, mental depression, schizophrenia and anxiety are highlighted. However, more detailed clinical trials along with a safety assessment of berberine are warranted for positioning the alkaloid in the treatment of neurological disorders.

Berberine inhibits adipogenesis in high-fat diet-induced obesity mice. Hu Y, Davies GE. Fitoterapia. 2009 Oct 25. [Epub ahead of print] PMID: 19861153 doi:10.1016/j.fitote.2009.10.010 Our previous studies illustrated that berberine inhibited adipogenesis in murine-derived 3T3-L1 preadipocytes and human white preadipocytes. In this study, the effects of berberine on the adipogenesis of high-fat diet-induced obesity (FD) or normal diet (ND) mice and possible transcriptional impact are investigated. The results demonstrated that in FD mice, berberine reduced mouse weight gain and food intake and serum glucose, triglyceride, and total cholesterol levels accompanied with a down-regulation of PPARgamma expression and an up-regulation of GATA-3 expression. Berberine had no adverse effects on ND mice. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent obesity.

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.

"ScienceDaily (Dec. 17, 2009) - A diet rich in methionine, an amino acid typically found in red meats, fish, beans, eggs, garlic, lentils, onions, yogurt and seeds, can possibly increase the risk of developing Alzheimer's disease, according to a study by Temple researchers. "When methionine reaches too high a level, our body tries to protect itself by transforming it into a particular amino acid called homocysteine," said lead researcher Domenico Praticò, an associate professor of pharmacology in the School of Medicine. "The data from previous studies show -- even in humans -- when the level of homocysteine in the blood is high, there is a higher risk of developing dementia. We hypothesized that high levels of homocysteine in an animal model of Alzheimer's would accelerate the disease." Using a seven-month old mouse model of the disease, they fed one group an eight-month diet of regular food and another group a diet high in methionine. The mice were then tested at 15 months of age -- the equivalent of a 70-year-old human.

The controversial place of vitamin C in cancer treatment. Verrax J, Calderon PB. Biochem Pharmacol. 2008 Dec 15;76(12):1644-52. Epub 2008 Sep 30. Review. PMID: 18938145 doi:10.1016/j.bcp.2008.09.024    

Novel omega -- 3-derived local mediators in anti-inflammation and resolution. Serhan CN. Pharmacol Ther. 2005 Jan;105(1):7-21. Review. PMID: 15626453 doi:10.1016/j.pharmthera.2004.09.002