Part 2: Vitamin D Update 2010

Missouri State Chiropractors Association District II Andrew S. Bonci, BA, DC Private Practice of Chiropractic Instructor, National American University www.drbonci.com

We're All Connected www.drbonci.com

Vitamin D Status as an Evolutionary Pressure www.drbonci.com

Skin Color and Evolution ● Some authors question if vitamin D deficiency leads to sufficient health problems to act as a selection pressure. Med Hypotheses. 2009 Aug 28 www.drbonci.com

Skin Color and Vitamin D ● “... vitamin D deficiency is sufficient to pose as a potent selection pressure for lighter skin colour. ● Vitamin D deficiency manifesting as rickets and osteomalacia are sufficient to impair reproductive success, but additionally, animal studies and some clinical observations suggest that vitamin D may have more direct impact on human fertility. Med Hypotheses. 2009 Aug 28 www.drbonci.com

Skin Color and Vitamin D ● Vitamin D deficiency may lead to a whole host of clinical conditions which impair health and increase mortality rates: increase susceptibility to bacterial and viral infections; rickets, osteomalacia and osteoporosis, with increased risk of falls and fractures; increased risk of cancers; hypertension and cardiovascular disease; maturity onset diabetes; autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and Type 1 diabetes; and gum disease. Med Hypotheses. 2009 Aug 28 www.drbonci.com

Skin Color and Vitamin D ● We submit that at higher latitudes, lighter skin color evolved to facilitate vitamin D production under conditions of low ultra-violet B radiation in order to avoid a plethora of ill health, reproductive difficulties and early mortality. Med Hypotheses. 2009 Aug 28 www.drbonci.com

Vitamin D and Cancers www.drbonci.com

● It is projected that raising the minimum year-around serum 25(OH)D level to 40 to 60 ng/mL would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three fourths of deaths from these diseases in the United States and Canada, based on observational studies combined with a randomized trial. ● Such intakes also are expected to reduce case-fatality rates of patients who have breast, colorectal, or prostate cancer by half. There are no unreasonable risks from intake of 2000 IU per day of vitamin D3, or from a population serum 25(OH)D level of 40 to 60 ng/mL. The time has arrived for nationally coordinated action to substantially increase intake of vitamin D and calcium. www.drbonci.com

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Colorectal Cancer www.drbonci.com

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Skin Cancer Protection ● Skin cancers are known to be associated with sun exposure, whereas sunlight through the production of vitamin D may protect against some cancers. (95%CI=0.50-0.67). ● Vitamin D production in the skin seems to decrease the risk of several solid cancers (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). Eur J Cancer. 2007 Jul;43(11):1701-12. www.drbonci.com

“The killing of tumor cells primarily by cytolysis in SR/CR mice was extremely rapid and effective, yet was achieved with profound selectivity, with most normal cells being unharmed.” Zheng Cui et. al. Proc Natl Acad Sci U S A. 2003 May 27; 100(11): 6682–6687. www.drbonci.com

Vitamin D & Ovarian Cancer ● The maintenance of telomere length is required for continued cell proliferation, and approximately 85-90% of human cancers, including ovarian epithelial cancers (OCa), show high activity of telomerase. ● In the present study we report that 1,25-dihydroxyvitamin D(3) (1,25(OH)(2) VD)(3)induces OCa cell apoptosis by down- regulating telomerase. J Biol Chem. 2004 Dec 17;279(51):53213-21. www.drbonci.com

Vitamin D Prostate Cancer ● Combination treatment with 1alpha,25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells. ● The results of the present study provide evidence on the molecular mechanism of the inhibition of cell growth by these agents, and they could be novel therapeutic agents for prostate cancer. Mol Cancer Ther. 2003 Aug;2(8):739-46. www.drbonci.com

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Breast Cancer www.drbonci.com

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Prevalence of Low Vitamin D 40 In this study of vitamin D 38.5 n = 512 status in 512 women: 37.5 ● 37.5% were deficient 30 ● 38.5% were insufficient Percentage ● 24% were adequate 20 24 Adequate is 30 ng/mL or higher (73 nmol/L). 10 0 Deficient Insufficient Adequate Vitamin D Status CA: A Cancer Journal for Clinicians. 2008 Sep/Oct;58:264-265. www.drbonci.com

Vitamin D and Breast Cancer Survival • Women with breast 2.0 cancer who had n = 512, 12 yrs 1.94 Cancer Free Survival (RR) adequate serum vitamin D levels (30+ ng/mL) 1.5 had nearly twice the survival rate after 12 1.0 years of follow-up than 1.00 vitamin D deficient (<20 0.5 ng/mL) women. 0.0 Low Adequate Serum Vitamin D Status CA: A Cancer Journal for Clinicians. 2008 Sep/Oct;58:264-265. www.drbonci.com

D, Season and Survivability ● Patients diagnosed during the summer and autumn had the best prognosis (Ralative risk (RR) death 0.8; 95% CI 0.75- 0.85). ● The seasonal effect on prognosis may be related to the seasonal variations of calcidiol (the marker of vitamin D status). J. Prostate. 2007 Sep 1;67(12):1362-70. www.drbonci.com

Vitamin D and Cancer Prevention www.drbonci.com

New Emerging Serum Vitamin D Norms Vitamin D status (ng/dL) (nmol/L) Deficient <20 <50 (high risk) Insufficient 20-29 50-72 (moderate risk) Adequate 30 or higher 73 or higher (low risk) Serum vitamin D test results (25-Hydroxyvitamin D) are shown in these two units. www.drbonci.com

Cardiovascular Disease www.drbonci.com

In summary, the results of the present study suggest that moderate to severe vitamin D deficiency is a risk factor for developing cardiovascular disease. These findings may have potentially broad public health implications, given the high prevalence of vitamin D deficiency in developed countries, the contribution of lifestyle and geography to vitamin D status, and the ease, safety, and low cost of treating vitamin D deficiency. www.drbonci.com

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Vitamin D and Infections www.drbonci.com

Infection and Deficiency ● Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human immunity. ● 1,25(OH)2D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the 'oxidative burst' potential of macrophages. Epidemiol Infect. 2006 Dec;134(6):1129-40. www.drbonci.com

Historical studies: cod liver oil prevents respiratory infections ● In the 1930’s, Vitamin A was investigated for its anti- infective properties using Cod liver oil, (which is also abundant in Vitamin D) ● Five studies using cod liver oil, (involving over 7,000 subjects), showed that cod liver oil reduced respiratory infections ● Cod liver oil given to 185 adults for four months reduced colds by 50%; Holmes AD, et al. Journal of Industrial and Engineering Chemistry 1932; 24; 1058-1060. ● In a five year study, cod liver reduced industrial absenteeism caused by colds and respiratory illness; days of missed work was reduced by 30%. (n=3031) Homes AD, et al. Industrial Medicine 1936; 5: 359-361. www.drbonci.com

Vitamin D Pharmacology ● Theoretically, pharmacological doses of vitamin D (2,000 IU per kg per day for three days) may produce enough of the naturally occurring antibiotic cathelicidin to cure common viral respiratory infections, such as influenza and the common cold, but such a theory awaits further science. Altern Med Rev. 2008 Mar;13(1):6-20. www.drbonci.com

Broad-Spectrum Antibiotic ● One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. ● Natural vitamin D levels, those found in humans living in a sun-rich environment, are between 40-70 ng per ml, levels obtained by few modern humans. Altern Med Rev. 2008 Mar;13(1):6-20. www.drbonci.com

Anti-Microbial Peptides ● Perhaps most importantly, it dramatically stimulates the expression of potent antimicrobial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. ● Vitamin D deficiency predisposes children to respiratory infections. Epidemiol Infect. 2006 Dec;134(6):1129-40. www.drbonci.com

Influenza is a seasonal illness Weekly consultation rates for clinically diagnosed flu www.drbonci.com Cannell JJ, Vieth R, Umhau JC,et al. Epidemiol Infect. 2006

The seasonal and latitudinal distribution of outbreaks of type A influenza in the world, 1964-1975 www.drbonci.com (WHO Data)

Seasonal variation of 25(OH)D levels www.drbonci.com Cannell JJ, Vieth R, Umhau JC,et al. Epidemiol Infect. 2006

Ultraviolet Light (UVR) Effects Immunity ● A sub-erythemal dose of UVR for 6-8 weeks doubled phagocytic activity in 21 children with recurrent respiratory tract infections. Krause R, et al. In: Holick MF and Jung EG, eds. Biological Effects of Light. Kluver Academic Publishers, 1998: pp. 49-51. ● Sub-erythemal doses of UVR (x5) increased polymorphonuclear chemotaxis in healthy volunteers. Csato M et al., British Journal of Dermatology 1984;111: 567-570. ● 410 athletes who received sub-erythemal doses of UVR (twice a year for three years) had more salivary IgA, IgG and IgM; 50% less respiratory viral infections, 300% fewer absence days and 30% shorter illness than did 446 non-irradiated control athletes. Gigineishvili GR, et al. Voprosy Kurortologii, Fizioterapii, i Lechebnoĭ Fizicheskoĭ Kultury 1990 May-Jun;(3):30-3. ● Dutch children with the most sun exposure were half as likely to develop cough, and a third as likely to develop rhinitis, compared to less sun exposed children. Termorshuizen F, et al. Photodermatology, Photoimmunology and Photomedicine 2004; 20: 270-271. www.drbonci.com

Vitamin D3 supplements eliminate the winter excess incidence of cold / flu Number of patients reporting colds / flu www.drbonci.com JOHN F. ALOIA AND MELISSA LI-NG, 2007, Epidemiology and Infection

Vitamin D Effects Immunity ● Vitamin D modulates the macrophage response, preventing the release of excessive inflammatory cytokines and chemokines Hewison M, et al. Molecular and Cellular Endocrinology 2004; 215: 31-38. Helming L, et al. Blood 2005; 106: 4351-4358. ● Vitamin D promotes macrophage production of specific surface antigens, the lysosomal enzyme acid phosphatase, and the secretion of H2O2 (which is antimicrobial), but vitamin D deficiency decreases these functions. 1986; 136: 1049-1053. Abu-Amer Y, Bar-Shavit Z. Cellular Immunology 1993; 151: 356-368. Cohen MS, et al. Journal of Immunology ● Vitamin D stimulates genetic expression of antimicrobial peptides, which have broad-spectrum antimicrobial activity and inactivate influenza virus. Wang TT, et al. Journal of Immunology 2004; 173: 2909-2912. Gombart AF et al, The FASEB Journal 2005; 19: 1067-1077. Liu PT, et al. 2006; 311: 1770-1773. Reddy KV et al, International Journal of Antimicrobial Agents 2004; 24: 536- 547. Hiemstra PS, et al. Current Pharmaceutical Design 2004; 10: 2891-2905. Daher KA et al, Journal of Virology 1986; 60: 1068-1074. www.drbonci.com

Vitamin D Metabolism www.drbonci.com John Cannell and Bruce Hollis, Alternative Medicine Review Volume 13, Number 1 March 2008

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UVB … Baby! ● Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). ● An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. Epidemiol Infect. 2006 Dec;134(6):1129-40. www.drbonci.com

HAART and Hypovitaminosis D We hypothesize that highly active antiretroviral therapy (HAART) may directly affect bone remodelling and/or may indirectly affect vitamin D metabolism. J Nucl Med Mol Imaging. 2004 Mar;48(1):39-48. www.drbonci.com

Vitamin D and Diabetes www.drbonci.com

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Type-1-DM Odds www.drbonci.com

Intake of vitamin D and risk of type 1 Type-1-DM Odds diabetes: a birth-cohort study. Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Lancet. 2001 Nov 3;358(9292):1500-3. Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes. Ensuring adequate vitamin D supplementation for infants could help to reverse the increasing trend in the incidence of type 1 diabetes. www.drbonci.com

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Vitamin D Status in Neuro-Immune Disorders www.drbonci.com

Atopic Dermatitis ● A 2-week course of heliotherapy (HT) significantly improved vitamin D balance by increasing serum calcidiol concentration, and caused a marked healing of atopic dermatitis (AD). ● HT improves vitamin D balance and AD. Vähävihu K, Ylianttila L, Salmelin R, Lamberg-Allardt C, Viljakainen H, Tuohimaa P, Reunala T, Snellman E. Br J Dermatol. 2008 Jun;158(6):1323-8. www.drbonci.com

Neuro-Immune Impact ● “ ... vitamin D imbalance may lay the foundation for a range of adult disorders, including brain pathologies (Parkinson's disease, epilepsy, depression) and immune-mediated disorders (rheumatoid arthritis, type I diabetes mellitus, systemic lupus erythematosus or inflammatory bowel diseases). “ Psychoneuroendocrinology. 2009 Jun 20. www.drbonci.com

Vitamin D and SLE ● SLE patients have multiple risk factors for vitamin D deficiency and disease severity seems correlated with lower 25-OH vitamin D serum levels. ● Treatment of vitamin D deficiency could be particularly important in SLE patients due to concomitant insults on their tissues such as bone and in ... immunomodulatory effects exerted by vitamin D. Lupus. 2008;17(1):6-10. www.drbonci.com

A low vitamin D status has now been linked to several Th1- mediated autoimmune diseases, including multiple sclerosis, type 1 diabetes and rheumatoid arthritis, with the strongest evidence for the vitamin's protective role in multiple sclerosis. Med Hypotheses. 2009 Jul;73(1):94-6. Peyrin-Biroulet L, Oussalah A, Bigard MA www.drbonci.com

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Vitamin D and MS ● A protective effect of Vitamin D on multiple sclerosis is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. ● Moreover, high circulating levels of Vitamin D have been associated with lower risk of multiple sclerosis. Brain. 2009 May;132(Pt 5):1146-60. www.drbonci.com

Geography of MS www.drbonci.com

Vitamin D and MS ● “... 1,25(OH)(2)D(3) plays an important role in T cell homeostasis during the course of multiple sclerosis, thus making correction of its deficiency may be useful during treatment of the disease.” ● Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain. 2009 May;132(Pt 5):1146-60. www.drbonci.com

Vitamin D and Crohn's Disease ● Similarly to multiple sclerosis, we propose in CD the so-called north-south gradient may be partly explained by variations in the degree of sun exposure, with vitamin D being a "seasonal stimulus". ● These observations may yield a better understanding of the pathophysiology of Crohn's disease and pave the way for developing new therapeutic approaches for an incurable disease.” Med Hypotheses. 2009 Jul;73(1):94-6. www.drbonci.com

Vitamin D Status in Neuropsychological Disorders www.drbonci.com

Vitamin D and Brain Development ● There is growing evidence that low vitamin D impacts adversely on brain development. ● The current study investigated the impact of developmental vitamin D (DVD) deficiency on dopamine and serotonin metabolism in the neonatal rat brain. ● These results suggest that DVD-deficiency influences dopamine turnover during development. Neurosci Lett. 2009 Sep 18;461(2):155-8. www.drbonci.com

Prevalence of Infantile Autism Disease for Those Born Prior to 1985 vs. Effective Latitude 7 IAD Prevalence (cases/100,000) 6 5 4 3 2 1 30 35 40 45 50 55 60 Effective Latitude (degrees N) www.drbonci.com

Brain Function and D ● [In line with this] recent animal and human studies suggest that vitamin D insufficiency is associated with abnormal development and functioning of the CNS. ● Overall, imbalances in the calciferol system appear to cause abnormal function, including premature aging, of the CNS. Psychoneuroendocrinology. 2009 Aug 4. www.drbonci.com

Dementia & D Deficiency ● Clinical data suggest that vitamin D(3) insufficiency is associated with an increased risk of several CNS diseases, including multiple sclerosis, Alzheimer's and Parkinson's disease, seasonal affective disorder and schizophrenia. Psychoneuroendocrinology. 2009 Aug 4. www.drbonci.com

Vitamin D and Dementia ● ...low serum 25-hydroxyvitamin D [25(OH)D] has been associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which are either considered risk factors for dementia or have preceded incidence of dementia. ● The laboratory evidence includes several findings on the role of vitamin D in neuroprotection and reducing inflammation. J Alzheimers Dis. 2009 May;17(1):151-9. www.drbonci.com

Vitamin D and Cognitive Impairment ● 25-Hydroxyvitamin D deficiency was associated with cognitive impairment in this cohort of community- dwelling older women. Neurology. 2009 Sep 30 www.drbonci.com

Vitamin D and Depression ● Research indicates that vitamin D supplementation may decrease depressive symptoms during the winter months … This study suggests that supplemental vitamin D3 reduces depressive symptoms. Appl Nurs Res. 2009 Aug;22(3):221-5. www.drbonci.com

Seasonal Serotonin ● We showed that turnover of serotonin by the brain was lowest in winter (p=0.013). ● Moreover, the rate of production of serotonin by the brain was directly related to the prevailing duration of bright sunlight (r=0.294, p=0.010), and rose rapidly with increased luminosity. ● Our findings are further evidence for the notion that changes in release of serotonin by the brain underlie mood seasonality and seasonal affective disorder. Lancet. 2002 Dec 7;360(9348):1840-2. www.drbonci.com

Anticonvulsants & Osteomalacia ● The study suggests that exposure to sunshine in our patients probably prevented the development of anticonvulsant- induced osteomalacia or rickets. Vitamin D metabolism and anticonvulsant therapy: effect of sunshine on incidence of osteomalacia. Williams C, Netzloff M, Folkerts L, Vargas A, Garnica A, Frias J. South Med J. 1984 Jul;77(7):834-6, 842. www.drbonci.com

Anticonvulsants & Osteomalacia ● Seventy-five percent of patients who had received anticonvulsants for more than ten years had osteomalacia. ● The single most costly medical problem at the school is the treatment of pathologic bone fractures due to demineralized bone. Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children. Tolman KG, Jubiz W, Sannella JJ, Madsen JA, Belsey RE, Goldsmith RS, Freston JW. Pediatrics. 1975 Jul;56(1):45-50. www.drbonci.com

Vitamin D Status in Athletic and Physical Performance www.drbonci.com

Athletic Performance ● Vitamin D also increases the size and number of Type II (fast twitch) muscle fibers. Most cross-sectional studies show that 25(OH)D levels are directly associated with musculoskeletal performance in older individuals. ● Most randomized controlled trials, again mostly in older individuals, show that vitamin D improves physical performance. J. Med Sci Sports Exerc. 2009 May;41(5):1102-10. www.drbonci.com

Athletic Performance ● Peak athletic performance may occur when 25(OH)D levels approach those obtained by natural, full-body, summer sun exposure, which is at least 50 ng/mL. ● Such 25(OH)D levels may also protect the athlete from several acute and chronic medical conditions. J. Med Sci Sports Exerc. 2009 May;41(5):1102-10. www.drbonci.com

Pulmonary Disorders www.drbonci.com

Vitamin D and Asthma ● A number of genes involved in the vitamin D pathway demonstrate modest levels of association with asthma and atopy. Respir Res. 2009 Oct 24;10(1):98. www.drbonci.com

D and Lung Function ● Vitamin D appears capable of inhibiting pulmonary inflammatory responses while enhancing innate defense mechanisms against respiratory pathogens. Clin Exp Immunol. 2009 Oct;158(1):20-5. www.drbonci.com

Lung Disease and D ● Chronic lung diseases such as asthma and chronic obstructive lung disease have also been linked to vitamin D on a genetic basis. ● A recent observational study notes a significant association between vitamin D deficiency and decreased pulmonary function tests in a large ambulatory population. Can Respir J. 2009 May-Jun;16(3):75-80. www.drbonci.com

Lung Disease and D ● Various cytokines, cellular elements, oxidative stress and protease/antiprotease levels appear to affect lung fibroproliferation, remodelling and function, which may be influenced by vitamin D levels. Can Respir J. 2009 May-Jun;16(3):75-80. www.drbonci.com

Vitamin D and Musculoskeletal Disease www.drbonci.com

Lower Back Pain ● Common manifestations of vitamin D deficiency are symmetric low back pain, proximal muscle weakness, muscle aches, and throbbing bone pain elicited with pressure over the sternum or tibia. ● The goal of treatment is to normalize vitamin D levels to relieve symptoms and decrease the risk of fractures, falls, and other adverse health outcomes. Recognition and management of vitamin D deficiency. Bordelon P, Ghetu MV, Langan RC. Am Fam Physician. 2009 Oct 15;80(8):841-6. www.drbonci.com

Osteomalacia ● Vitamin D deficiency and osteomalacia should be considered in the differential diagnosis of patients with musculoskeletal pain, fibromyalgia, chronic fatigue syndrome, or myositis. ● There is a need for better education of health professionals and the general public regarding the optimization of vitamin D status in the care of rehabilitation patients. Vitamin d and rehabilitation: improving functional outcomes. Shinchuk LM, Holick MF. Nutr Clin Pract. 2007 Jun;22(3):297-304. www.drbonci.com

Osteomalacic Myopathy ● Our objectives were to describe features of myopathy associated with Vitamin D deficiency and examine the contributing factors leading to osteomalacic myopathy in our region. ● Remarkable recovery was documented in all patients following oral cholecalciferol and calcium supplementation. ● The diagnosis is frequently delayed or missed. Severe proximal myopathy with remarkable recovery after vitamin D treatment. Al-Said YA, Al-Rached HS, Al-Qahtani HA, Jan MM. Can J Neurol Sci. 2009 May;36(3):336-9. www.drbonci.com

Osteomalacic Cephalgia ● The prevalence of tension-type headache and vitamin D deficiency are both very high in the general population. ● The headache and osteomalacia ... responded to vitamin D and calcium supplementation. ● The improvement in the headache was much earlier than the improvements in the symptom complex of osteomalacia. Chronic tension-type headache with vitamin D deficiency: casual or causal association? Prakash S, Shah ND. Headache. 2009 Sep;49(8):1214-22. www.drbonci.com

Osteomalacic Heel Pain ● We report five patients with nutritional osteomalacia who presented with the symptoms and signs of plantar fasciitis. All the patients were Asian vegetarian women. All improved with treatment of the osteomalacia, albeit slowly in two cases. Nutritional osteomalacia presenting with plantar fasciitis. Paice EW, Hoffbrand BI. J Bone Joint Surg Br. 1987 Jan;69(1):38-40. www.drbonci.com

Physical Rehabilitation ● Vitamin D inadequacy is pandemic among rehabilitation patients in both inpatient and outpatient settings. ● Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and worsens proximal muscle strength and postural sway. Nutr Clin Pract. 2007 Jun;22(3):297-304. www.drbonci.com

Vitamin D and Walking ● In the resulting models for 6- minute walking distance, calcidiol was a significant predictor, which tended to be more marked in the underweight patients than in the normal-weight ones. Exp Lung Res. 2009 Aug;35(6):524-38. www.drbonci.com

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D, Folate and Falls ● Vitamin D was related to most functional and balance measurements. ● Serum folate was protective against falls. For every 1 ng/ml increase in serum folate the occurrence of falls decreased by 19%.” ● Nutritional status in relation to balance and falls in the elderly: a preliminary look at serum folate. Ann Nutr Metab. 2009;54(1):59-66. www.drbonci.com

Glucocorticoids and Vitamin D ● The present results show that one of the means by which large doses of adrenal corticoids alter intestinal calcium transport is by stimulating the further metabolism of 1,25- dihydroxyvitamin D(3) to a more polar, biologically inactive intestinal metabolite. Proc Natl Acad Sci U S A. 1974 Aug;71(8):2996-3000. www.drbonci.com

Vitamin D and UCTD In patients with Undifferentiate Connective Tissue Disease (UCTD), a seasonal variance in levels of 25(OH)D3 was identified and showed that these levels were significantly lower than in controls during the corresponding seasons … vitamin D deficiency in UCTD patients may play a role in the subsequent progression into well- defined CTDs. Arthritis Res Ther. 2008;10(5):R123. www.drbonci.com

Early surgical repair, control of secondary hyperparathyroidism, early use of vitamin D analogs, and total parathyroidectomy with or without autotransplantation analogs of part of the parathyroid gland, can treat and prevent tendon rupture or re-rupture with satisfactory results. [J Formos Med Assoc 2006;105(11):941–945] www.drbonci.com

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Vitamin D and Aging www.drbonci.com

Age Related Changes ● These results indicate that there is a marked decrease in the capacity of the vitamin D- deficient adult rat to convert 25- hydroxyvitamin D3 to 1,25- dihydroxyvitamin D3. This is probably due to the decreased capacity of the adult kidney to 1-hydroxylate 25- hydroxyvitamin D3. J Clin Invest. 1980 Nov;66(5):1118-23. www.drbonci.com

Vitamin D and Aging ● Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. ● Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation. ● Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases. Am J Clin Nutr. 2007 Nov;86(5):1420-5. www.drbonci.com

Economic Burden of Vitamin D Deficiency www.drbonci.com

Worth the Skin Cancer Risk? ● The U.S. economic burden due to vitamin D insufficiency from inadequate exposure to solar UVB irradiance, diet, and supplements was estimated at $40-56 billion in 2004, whereas the economic burden for excess UV irradiance was estimated at $6-7 billion. Photochem Photobiol. 2005 Nov-Dec;81(6):1276-86. www.drbonci.com

Reduced Economic Burden ● These results suggest that increased vitamin D through UVB irradiance, fortification of food, and supplementation could reduce the health care burden in the United States, UK, and elsewhere. Photochem Photobiol. 2005 Nov-Dec;81(6):1276-86. www.drbonci.com

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Economic Burden of Deficiency ● US economic burden due to vitamin D insufficiency from inadequate exposure to solar UVB irradiance, diet and supplements was estimated at $40 billion to $56 billion in 2004, whereas the economic burden for excess UV irradiance was estimated at $6 billion to $7 billion. Adv Exp Med Biol. 2008;624:16-30. www.drbonci.com

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Deficiency Death Toll ● We estimate that 50,000- 63,000 individuals in the United States and 19,000- 25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D. Photochem Photobiol. 2005 Nov-Dec;81(6):1276-86. www.drbonci.com

An Ethical Question? ● The recent discovery--from a meta-analysis of 18 randomized controlled trials-- that supplemental cholecalciferol (vitamin D) significantly reduces all- cause mortality emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency. Altern Med Rev. 2008 Mar;13(1):6-20. www.drbonci.com

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Acknowledgements ● Cannell JJ ● Vieth R ● Holick MF ● Grant WB ● Madronich S ● Garland CF ● Giovannucci E www.drbonci.com

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Part 2: Vitamin D Update 2010

by Andrew Bonci on Apr 08, 2010

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Part 2: Vitamin D Update 2010 — Presentation Transcript