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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

Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD. Bone. 2009 Nov;45(5):870-5. Epub 2009 Jul 23. PMID: 19631774 doi:10.1016/j.bone.2009.07.015 Cholecalciferol supplementation resulted in a 31% greater increase in total HPLC-measured 25OHD (p=0.010) and 52% greater rise in RIA-measured 25OHD (p0.05). In vitamin D-insufficient hip fracture patients, supplementation with cholecalciferol 1000 IU/day for three months was more effective in increasing serum 25OHD than an equivalent dose of ergocalciferol. However, the lack of difference in PTH lowering between calciferol treatments raises questions about the biological importance of this observation.

The bioavailability of vitamin D from fortified cheeses and supplements is equivalent in adults. Wagner D, Sidhom G, Whiting SJ, Rousseau D, Vieth R. J Nutr. 2008 Jul;138(7):1365-71. PMID: 18567762 Compared with baseline, serum parathyroid hormone decreased with both fortification (P = 0.003) and supplementation (P = 0.012). These data demonstrate that vitamin D is equally bioavailable from fortified hard cheeses and supplements, making cheese suitable for vitamin D fortification.

White button mushrooms (Agaricus bisporus), although often considered a poor relation of exotic, expensive varieties like maitake and matsutake mushrooms, provide as much or even more anti-oxidant activity as their costly cousins. Researchers at the Institut National de la Recherche Agrinomique in France found that the free radical scavenging ability of the humble button mushroom was equivalent to, if not higher than, that of maitake and the matsutake mushrooms - both of which are highly prized in Japanese cuisine for their reputed ability to lower blood pressure and fight cancer.

Together, the earlier data and the data of Heaney et al indicate that an oral dose of vitamin D2 or vitamin D3 would lead to a comparable increase in circulating 25(OH)D concentrations in children and adults when the initial 25(OH)D3 concentrations in the groups are similar and when equivalent oral vitamin D doses expressed per kilogram body weight/d are given. Serum 25-hydroxyvitamin D response to oral vitamin D intake in children. Zittermann A. Am J Clin Nutr. 2003 Sep;78(3):496-7. PMID: 12936937

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

Stevia comes from an herb in the chrysanthemum family called Stevia rebaudiana. It is native to Paraguay, also grows in Brazil and Argentina, and is cultivated in China. The leaves have been used for centuries by native peoples to make sweet teas, or to sweeten other foods, with no evidence of harm. It is available in the United States, and the European Union as a dietary supplement and is sold here in whole-leaf form or as stevioside, the extracted sweet principle, sold as a granular white powder. The powder has very few calories but is so sweet that to use it, you must dissolve it in water, then dispense the solution by drops. A teaspoon of the liquid is equivalent in sweetness of a whole cup of sugar. Stevia is safe for diabetics and is widely used as a nonnutritive sweetener around the world.

Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status. Hollis BW, Wagner CL, Drezner MK, Binkley NC. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):631-4. Epub 2007 Jan 10. PMID: 17218096 In the present study, we sought to investigate what circulating 25(OH)D levels would result in populations exhibiting no substrate limitations to the vitamin D-25-hydroxylase. To perform this, we chose two distinct populations. The first were individuals from a year-found sunny environment who spent a good deal of time outdoors. The second were a group of lactating women receiving a substantial daily oral dose of vitamin D3. Surprisingly, a study such as this previously had not been undertaken. There are several reasons for this. First, finding a group of sun-exposed individuals is not an easy task; in fact, we had to go to Hawaii to find them. Secondly, very few studies have been performed where subjects actually received adequate vitamin D3 supplementation to make them replete. Finally, it is very difficult and costly to measure circulating vitamin D3 and relate it to circulating 25(OH)D. The results of our study are far-reaching. This study also demonstrates that individuals can be vitamin D deficient with significant sun exposure if the skin area exposed is limited as was suggested several years ago (19). Finally, whether one receives their vitamin D3 orally or through UV exposure, the vitamin D-25-hydroxylase appears to handle it in an equivalent fashion with respect to maintaining circulating 25(OH)D levels. Thus, we believe that the relationship between circulating vitamin D and 25(OH)D may define adequate nutritional vitamin D status.

A diet high in fruit and vegetables, especially organically grown ones, may protect against cancer and heart disease and could be equivalent in this respect to taking a low dose of aspirin every day, scientists say.\n\nFruit and vegetables are known to have high levels of salicylates, which are also the active anti-inflammatory ingredient of aspirin. Vegetarians meanwhile are known to have low rates of cancer, as well as having higher levels of salicylates in their bodies.

March 23, 2009 -- Men and women who eat higher amounts of red meat and processed meat have a higher risk of dying from cancer, heart disease, and other causes compared to those who eat less, according to a new study. Those in the study who ate the most red meat took in about 4.5 ounces a day -- the equivalent of a small steak.

Researchers at the University of California, Berkeley, have identified a gene that plays a critical regulatory role in the process of converting dietary carbohydrates to fat. In a new study, they disabled this gene in mice, which consequently had lower levels of body fat than their normal counterparts, despite being fed the equivalent of an all-you-can-eat pasta buffet. The authors of the study, to be published in the March 20 issue of the journal Cell, say the gene, called DNA-PK, could potentially play a role in the prevention of obesity related to the over-consumption of high-carbohydrate foods, such as pasta, rice, soda and sugary snacks..

"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. "

"From 1955 to 1990, all infants in East Germany received 600,000 IU of Vitamin D every three months for a total of 3,600,000 IU at age 18 months. With the 400 IU/day recommendation of the American Pediatric Association in mind, I ran across this amazing paper while surfing Medline for Vitamin D. According to this paper, all infants in the German Democratic Republic (East Germany) received dangerously high doses of Vitamin D every three months in their doctors office. The policy was in place for 35 years. The first 600,000 IU dose was given at three months and then every three months until the child was 18 months of age. This works out to an average of 6,000 IU per day (actually, for several technical reasons it is not equivalent) for 18 months. The authors collected blood before the dose and then 2 weeks after the quarterly dose to obtain 25(OH)D, 1,25(OH)D, and calcium levels on a total of 43 infants. Before the first dose, at 3 months of age, the average infant was extremely deficient (median 25(OH)D of 7 ng/ml). Two weeks after the first dose the average 25(OH)D level was 120 ng/ml, the second dose 170 ng/ml, the third dose, 180 ng/ml, the fourth dose, 144 ng/ml, the fifth dose, 110 ng/ml and after the sixth and final dose, 3.6 million total units, at age 18 months, the children had mean levels of 100 ng/ml. That is, by the 15 and 18 month doses, the children were beginning to effectively handle these massive doses. The highest level recorded in any of the 43 infants was 408 ng/ml at age 9 months, two weeks after the third 600,000 IU dose. Thirty-four percent of the infants had at least one episode of hypercalcemia but only 3 had an elevated serum 1,25(OH)D. The authors reported that all the infants appeared healthy, even the infant with a level of 408 ng/ml, that is, no clinical toxicity was noted in any of these infants."

"Not everyone has access to pastured eggs. "Omega-3 eggs" come from hens fed an omega-3 enriched diet*. Not only do they have a much higher omega-3 content than conventional eggs, they also contain less AA. One study found that omega-3 eggs contain 39% less AA than conventional and organic eggs. Omega-3 eggs were also rich in short- and long-chain omega-3 fats. Omega-3 eggs are certainly not nutritionally equivalent to pastured eggs, but they're a step in the right direction. "

"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.

In an article published online on January 4, 2010 in the Journal of Agricultural and Food Chemistry, Robert Krikorian of the University of Cincinnati, along with his colleagues from the US and Canadian Departments of Agriculture, report that consuming blueberry juice was associated with improvements in learning and memory in individuals with age-related memory decline. The trial enrolled five men and four women over the age of 70 who reported forgetfulness and memory lapses characteristic of early memory decline. Participants were given the equivalent of 2 to 2 ½ cups of a commercially available blueberry juice daily for 12 weeks. Cognitive assessments were conducted at the beginning of the study and during the final week of the trial. At the study's conclusion, learning and recall were improved, and depressive symptoms and glucose levels tended to be reduced. When subjects who received blueberry juice were compared with a demographically matched sample who received a placebo beverage in a companion trial, test scores for learning ability were significantly better.

The Diet-Heart Hypothesis: Subdividing Lipoproteins Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids. Lipoproteins Can be Subdivided into Several Subcategories In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source): The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease. Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder. Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily

High-dose vitamin D3 supplementation in a cohort of breastfeeding mothers and their infants: a 6-month follow-up pilot study. Wagner CL, Hulsey TC, Fanning D, Ebeling M, Hollis BW. Breastfeed Med. 2006 Summer;1(2):59-70. PMID: 17661565 doi:10.1089/bfm.2006.1.59. Objective: To examine the effect of high-dose maternal vitamin D3 (vitD) supplementation on the nutritional vitD status of breastfeeding (BF) women and their infants compared with maternal and infant controls receiving 400 and 300 IU vitD/day, respectively. Design: Fully lactating women (n = 19) were enrolled at 1-month postpartum into a randomized- control pilot trial. Each mother received one of two treatments for a 6-month study period: 0 or 6000 IU vitD3 plus a prenatal vitamin containing 400 IU vitD3. The infants of mothers assigned to the control group received 300 IU vitD3/day; those infants of mothers in the high-dose group received 0 IU (placebo). Maternal serum and milk vitD and 25(OH)D were measured at baseline then monthly; infant serum vitD and 25(OH)D were measured at baseline, and months 4 and 7. Urinary calcium/creatinine ratios were measured monthly in both mothers and infants. Dietary and BF history and outdoor activity questionnaires were completed at each visit. Changes in skin pigmentation were measured by spectrophotometry. Data were analyzed using chi-square, t-test, and analysis of variance (ANOVA) on an intent-to-treat basis. Conclusion: With limited sun exposure, an intake of 400 IU/day vitamin D3 did not sustain circulating maternal 25(OH)D levels, and thus, supplied only extremely limited amounts of vitamin D to the nursing infant via breast milk. Infant levels achieved exclusively through maternal supplementation were equivalent to levels in infants who received oral vitamin D supplementation. Thus, a maternal intake of 6400 IU/day vitamin D elevated circulating 25(OH)D in both mother and nursing infant.

Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia -- Krauss et al. 83 (5): 1025 -- American Journal of Clinical Nutrition Changes in peak LDL diameter (Table 2) and mass concentrations of LDL subfractions (Table 3) induced by each of the diets were reflected by changes in the proportions of subjects exhibiting LDL subclass pattern B (Figure 2). There were linear reductions in the prevalence of pattern B as a function of reduced carbohydrate intake after both the stable-weight and weight-loss periods. However, the slopes of these relations differed (P = 0.04) such that the magnitude of the reduction in expression of pattern B induced by weight loss increased in association with the percentage of carbohydrate intake. Conclusions: Moderate carbohydrate restriction and weight loss provide equivalent but nonadditive approaches to improving atherogenic dyslipidemia. Moreover, beneficial lipid changes resulting from a reduced carbohydrate intake were not significant after weight loss. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. Am J Clin Nutr. 2006 May;83(5):1025-31; quiz 1205. Erratum in: Am J Clin Nutr. 2006 Sep;84(3):668. PMID: 16685042