Group items tagged

Nutrients, endpoints, and the problem of proof. Heaney RP. 2008 W. O. Atwater Memorial Lecture J Nutr. 2008 Sep;138(9):1591-5. PMID: 18716155 To sum up, I think that there would be general agreement to the effect that nutrition is important, despite the fact that the still growing number of failed trials of individual nutrients might suggest that no nutrient actually made much of a difference, a conclusion that is absurd on its face and ought to have alerted us to the possibility that there was something wrong with how we were investigating the matter. To provide the proof needed to sustain revised intake recommendations, we shall have to find a design better suited to nutrients than the randomized controlled trial as currently implemented, and we need to develop a series of global indices, nutrient by nutrient, which better capture the polyvalent nature of most nutrients. Perhaps it would be useful for the ASN, in collaboration with concerned governmental entities such as the USDA, to convene a workshop to address these structural issues. Such deliberation may well be arduous and frustrating, but it is terribly important and, in my view, well worth the effort.

"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)."

Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Lancet. 2007 Mar 31;369(9567):1090-8. Erratum in: Lancet. 2007 Jul 21;370(9583):220. PMID: 17398308 doi:10.1016/S0140-6736(07)60527-3 Interpretation EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients

Benefit-risk assessment of vitamin D supplementation. Bischoff-Ferrari HA, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett WC. Osteoporos Int. 2009 Dec 3. [Epub ahead of print] PMID: 19957164 Conclusion Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.

[Vitamin K2] Ishida Y. Clin Calcium. 2008 Oct;18(10):1476-82. Review. Japanese. PMID: 18830045 "Vitamin K2 has been approved for the treatment of osteoporosis in Japan since 1995. Vitamin K2 treatment in osteoporosis has been shown to inhibit the occurrence of new bone fractures and to maintain BMD. The uniqueness of the prevention of bone fractures by vitamin K2 is that there has been no direct evidence of the relationship between increase of BMD and a decrease in the occurrence of bone fractures. A recent systematic review of seven Japanese randomized controlled trials by Cockayne has also shown that supplementation with phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone-4, is associated with increased BMD and reduced fracture incidence. To confirm these results, a larger well design RCT using fractures as the primary endpoint is clearly needed."

Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Bischoff-Ferrari HA. Adv Exp Med Biol. 2008;624:55-71. Review. PMID: 18348447 DOI: 10.1007/978-0-387-77574-6_5 Recent evidence suggests that higher vitamin D intakes beyond current recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, admission to nursing home, fractures, cancer prevention and incident hypertension. For all endpoints, the most advantageous serum levels for 25(OH)D appeared to be at least 75 nmol/l (30 ng/ml) and for cancer prevention, desirable 25(OH)D levels are between 90-120 nmol/l (36-48 ng/ml). An intake of no less than 1000IU (25 meg) of vitamin D3 (cholecalciferol) per day for all adults may bring at least 50% of the population up to 75 nmol/l. Thus, higher doses of vitamin D are needed to bring most individuals into the desired range. While estimates suggest that 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of 2000 IU or higher doses for the total adult population need to be addressed in future studies.

Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. Whiting SJ, Calvo MS. J Nutr. 2005 Feb;135(2):304-9. Review. PMID: 15671232 In summary, vitamin D has emerged as a critical nutrient for which there is a compelling health need to establish adequate dietary guidelines in North America and worldwide given the increasing evidence of vitamin D deficiency and insufficient links to risk of chronic disease. We strongly argue that now there are enough data to consider setting an estimated average requirement for vitamin D and to recognize the crucial need for more research to determine the role of vitamin D in noncalciotropic functions and prevention of chronic diseases