X-Message-Number: 29508 Date: Sun, 13 May 2007 09:48:11 -0700 (PDT) From: Subject: life extension with vitamin D: Part 2 J Am Geriatr Soc. 2007 Feb;55(2):234-9. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts 02131, USA. OBJECTIVES: To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents. DESIGN: Secondary data analysis of a previously conducted randomized clinical trial. SETTING: Seven hundred twenty-five-bed long-term care facility. PARTICIPANTS: One hundred twenty-four nursing home residents (average age 89). INTERVENTION: Participants were randomly assigned to receive one of four vitamin D supplement doses (200 IU, 400 IU, 600 IU, or 800 IU) or placebo daily for 5 months. MEASUREMENTS: Number of fallers and number of falls assessed using facility incident tracking database. RESULTS: Over the 5-month study period, the proportion of participants with falls was 44% in the placebo group (11/25), 58% (15/26) in the 200 IU group, 60% (15/25) in the 400 IU group, 60% (15/25) in the 600 IU group, and 20% (5/23) in the 800 IU group. Participants in the 800 IU group had a 72% lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months (rate ratio=0.28; 95% confidence interval=0.11-0.75). No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups. CONCLUSION: Nursing home residents in the highest vitamin D group (800 IU) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses. Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group. PMID: 17302660 Mol Aspects Med. 2005 Jun;26(3):203-19. Vitamin D in the aging musculoskeletal system: an authentic strength preserving hormone. Montero-Odasso M, Duque G. Geriatric Medicine Program, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. Until recently, vitamin D was only considered as one of the calciotrophic hormones without major significance in other metabolic processes in the body. Several recent findings have demonstrated that vitamin D plays also a role as a factor for cell differentiation, function and survival. Two organs, muscle and bone, are significantly affected by the presence, or absence, of vitamin D. In bone, vitamin D stimulates bone turnover while protecting osteoblasts of dying by apoptosis whereas in muscle vitamin D maintains the function of type II fibers preserving muscle strength and preventing falls. Furthermore, two major changes associated to aging: osteoporosis and sarcopenia, have been also linked to the development of frailty in elderly patients. In both cases vitamin D plays an important role since the low levels of this vitamin seen in senior people may be associated to a deficit in bone formation and muscle function. In this review, the interaction between vitamin D and the musculoskeletal components of frailty are considered from the basic mechanisms to the potential therapeutic approach. We expect that these new considerations about the importance of vitamin D in the elderly will stimulate an innovative approach to the problem of falls and fractures which constitutes a significant burden to public health budgets worldwide. PMID: 15811435 Neurology. 2006 Dec 12;67(11):2005-14. Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact on bone. Mikati MA, Dib L, Yamout B, Sawaya R, Rahi AC, Fuleihan Gel-H. Adult and Pediatric Epilepsy Program, Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon. OBJECTIVE: To investigate the effects of two doses of vitamin D given over 1 year on bone density in ambulatory patients on long-term antiepileptic drug (AED) therapy. METHODS: We conducted two parallel, randomized, controlled trials in 72 adults (18 to 54 years old) and 78 children and adolescents (10 to 18 years) on long-term AED therapy. They received either low-dose vitamin D 400 IU/day or high-dose vitamin D 4,000 IU/day (adults) and 2,000 IU/day (children/adolescents). Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry. RESULTS: In adults, baseline BMD was lower than that of age- and gender-matched controls vs either a Western or an ethnically identical population. After 1 year, there were significant increases in BMD at all skeletal sites compared to baseline in the high-, but not in the low-dose treatment group. However, BMD at 1 year remained below normal. In children, baseline BMD was normal vs age- and gender-matched controls and showed significant and comparable increases in both treatment groups. CONCLUSIONS: In ambulatory adults on antiepileptic drugs, high-dose vitamin D therapy substantially increased bone mineral density at several skeletal sites. In children, both doses resulted in comparable increases in bone mass. PMID: 17159108 Osteoporos Int. 2007 Apr;18(4):401-7. Epub 2006 Dec 7. How to select the doses of vitamin D in the management of osteoporosis. Bischoff-Ferrari HA.Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Gloriastrasse 25, 8091, Zurich, Switzerland. The dose of vitamin D in the management of osteoporosis should be no less than 700-800 IU per day. An optimal dose of vitamin D should raise serum concentrations of 25(OH)D to the desirable range of at least 75 nmol/l. Higher intermittent oral doses of vitamin D may overcome low adherence. Vitamin D supplementation in the management of osteoporosis holds a significant public health potential because of its low cost, excellent tolerability, and combined musculo-skeletal benefits. Fall and fracture prevention with vitamin D is especially appealing in the treatment of older individuals at risk for fall-related fractures. However, bone density, strength, and function benefits with vitamin D include active and inactive subgroups of community-dwelling older men and women. Based on a recent expert panel and supportive evidence presented in this review, serum concentrations of at least 75 nmol/l 25(OH)D will be referred to as desirable. Today, desirable serum 25(OH)D levels of at least 75 nmol/l may only be reached in about one third of US older individuals and even fewer European older individuals. Two main factors discussed in this review may help public health efforts to ensure desirable vitamin D levels for fall and fracture prevention, including (1) a sufficient dose of vitamin D and (2) improved adherence to supplementation. PMID: 17151835 Med Hypotheses. 2007;68(5):1026-34. Epub 2006 Dec 4. Vitamin D toxicity redefined: vitamin K and the molecular mechanism. Masterjohn C.Weston A. Price Foundation, 4200 Wisconsin Ave., NW, Washington, DC 20016, United States. The dose of vitamin D that some researchers recommend as optimally therapeutic exceeds that officially recognized as safe by a factor of two; it is therefore important to determine the precise mechanism by which excessive doses of vitamin D exert toxicity so that physicians and other health care practitioners may understand how to use optimally therapeutic doses of this vitamin without the risk of adverse effects. Although the toxicity of vitamin D has conventionally been attributed to its induction of hypercalcemia, animal studies show that the toxic endpoints observed in response to hypervitaminosis D such as anorexia, lethargy, growth retardation, bone resorption, soft tissue calcification, and death can be dissociated from the hypercalcemia that usually accompanies them, demanding that an alternative explanation for the mechanism of vitamin D toxicity be developed. The hypothesis presented in this paper proposes the novel understanding that vitamin D exerts toxicity by inducing a deficiency of vitamin K. According to this model, vitamin D increases the expression of proteins whose activation depends on vitamin K-mediated carboxylation; as the demand for carboxylation increases, the pool of vitamin K is depleted. Since vitamin K is essential to the nervous system and plays important roles in protecting against bone loss and calcification of the peripheral soft tissues, its deficiency results in the symptoms associated with hypervitaminosis D. This hypothesis is circumstantially supported by the observation that animals deficient in vitamin K or vitamin K-dependent proteins exhibit remarkable similarities to animals fed toxic doses of vitamin D, and the observation that vitamin D and the vitamin K-inhibitor Warfarin have similar toxicity profiles and exert toxicity synergistically when combined. The hypothesis further proposes that vitamin A protects against the toxicity of vitamin D by decreasing the expression of vitamin K-dependent proteins and thereby exerting a vitamin K-sparing effect. If animal experiments can confirm this hypothesis, the models by which the maximum safe dose is determined would need to be revised. Physicians and other health care practitioners would be able to treat patients with doses of vitamin D that possess greater therapeutic value than those currently being used while avoiding the risk of adverse effects by administering vitamin D together with vitamins A and K. PMID: 17145139 J Bone Miner Res. 2007 Apr;22(4):509-19. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, Prynne CJ, Mishra GD, Shearer MJ. Nutrition Research Group, CVEU, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK. Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. INTRODUCTION: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age. MATERIALS AND METHODS: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. RESULTS: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 2 5-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). CONCLUSIONS: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation. PMID: 17243866 [Quick summary: It's probably a good idea to take 1,000 IU of vitamin D during the summer, and 2000 IU during the winter, as well as plenty of deep green vegetables or a supplement to provide adequate vitamin K as well.] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=29508