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Pharmacokinetics of a single, large dose of cholecalciferol. Ilahi M, Armas LA, Heaney RP. Am J Clin Nutr. 2008 Mar;87(3):688-91. PMID: 1832660 Conclusions: Cholecalciferol (100 000 IU) is a safe, effective, and simple way to increase calcidiol concentrations. The dosing interval should be ≤2 mo to ensure continuous serum calcidiol concentrations above baseline. Our study highlights that 100 000 IU cholecalciferol is a safe, efficient, and cost-effective means to increase calcidiol concentrations in the elderly. From this study we can safely recommend 100 000 IU cholecalciferol dosed every 2 mo in persons with moderate baseline calcidiol concentrations. However, in those persons with baseline calcidiol concentrations < 20 ng/mL, even this large dose will not adequately raise their calcidiol concentrations.

Serum vitamin D concentration and prostate cancer risk: a nested case-control study. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team. J Natl Cancer Inst. 2008 Jun 4;100(11):796-804. Epub 2008 May 27. PMID: 18505967 doi:10.1093/jnci/djn152 CONCLUSION: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. In summary, results from this large prospective study of men who underwent standardized prostate cancer screening in the context of a screening trial do not support the hypothesis that higher serum vitamin D status is associated with decreased risk of prostate cancer. The study showed no association of vitamin D level with nonaggressive disease; however, it raises the possibility that higher vitamin D level may be associated with increased risks for aggressive disease, although a clear monotonic dose-response relationship was lacking. Along with recent reports of adverse associations for higher vitamin D status and risk of pancreatic (32) and esophageal (33,34) cancer, caution should be taken in recommending high doses of vitamin D or sunlight exposure to the general public for prostate cancer prevention. Future analyses are warranted to confirm these results and to further clarify the effects of vitamin D on aggressive prostate cancer.

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

Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Stene LC, Joner G; Norwegian Childhood Diabetes Study Group. Am J Clin Nutr. 2003 Dec;78(6):1128-34. PMID: 14668274 Conclusion: Cod liver oil may reduce the risk of type 1 diabetes, perhaps through the antiinflammatory effects of long-chain n-3 fatty acids.

Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. Pilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, Boehm BO, Dobnig H. J Clin Endocrinol Metab. 2008 Oct;93(10):3927-35. Epub 2008 Aug 5. PMID: 18682515 doi:10.1210/jc.2008-0784 Conclusions: Low levels of 25(OH)D and 1,25(OH)2D are associated with prevalent myocardial dysfunction, deaths due to heart failure and SCD. Interventional trials are warranted to elucidate whether vitamin D supplementation is useful for treatment and/or prevention of myocardial diseases.

Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography.\nPilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, Boehm BO, Dobnig H.\nJ Clin Endocrinol Metab. 2008 Oct;93(10):3927-35. Epub 2008 Aug 5.\nPMID: 18682515

ScienceDaily (Dec. 5, 2009) - A new study has found that the amount of vitamin D in patients being treated for diffuse large B-cell lymphoma was strongly associated with cancer progression and overall survival. The results will be presented at the annual meeting of the American Society of Hematology in New Orleans. Also, several recent reports have concluded that vitamin D deficiency is associated with poor outcomes in other cancers, including breast, colon and head and neck cancer. This is the first study to look at lymphoma outcome

Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data. Diamond TH, Ho KW, Rohl PG, Meerkin M. Med J Aust. 2005 Jul 4;183(1):10-2. PMID: 15992330 Conclusions: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.

25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. Am J Clin Nutr. 2008 Jun;87(6):1738-42. PMID: 18541563 Conclusions: At physiologic inputs, there is rapid conversion of precursor to product at low vitamin D3 concentrations and a much slower rate of conversion at higher concentrations. These data suggest that, at typical vitamin D3 inputs and serum concentrations, there is very little native cholecalciferol in the body, and 25(OH)D constitutes the bulk of vitamin D reserves. However, at supraphysiologic inputs, large quantities of vitamin D3 are stored as the native compound, presumably in body fat, and are slowly released to be converted to 25(OH)D.

To conclude, our findings suggest an association between large-dose vitamin D supplementation in infancy and an increased risk of atopy, allergic rhinitis, and asthma later in life. Further study is required to determine whether these observations could imply that vitamin D supplementation in infancy may have long-term effects on immune regulation, or if they reflect some unmeasured determinants of vitamin D supplementation Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Hyppönen E, Sovio U, Wjst M, Patel S, Pekkanen J, Hartikainen AL, Järvelinb MR. Ann N Y Acad Sci. 2004 Dec;1037:84-95. DOI: 10.1196/annals.1337.013 PMID: 15699498

A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D William B. Grant Dermato-Endocrinology. Volume 1, Issue 1 January/February 2009 Pages: 25 - 33 The International Agency for Research on Cancer (IARC) released a report, Vitamin D and Cancer, on November 25, 2008. The report focused on the current state of knowledge and level of evidence of a causal association between vitamin D status and cancer risk. Although presenting and evaluating evidence for the beneficial role of UVB and vitamin D in reducing the risk of cancer, it discounted or omitted important evidence in support of the efficacy of vitamin D. The report largely dismissed or ignored ecological studies on the grounds that confounding factors might have affected the findings. The report accepted a preventive role of vitamin D in colorectal cancer but not for breast cancer.

High-dose oral vitamin D3 supplementation in the elderly. Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. Osteoporos Int. 2009 Aug;20(8):1407-15. Epub 2008 Dec 20. PMID: 19101755 Sixty-three elderly participants were randomized to three regimens of vitamin D supplementation: a 500,000-IU loading dose; the loading dose plus 50,000 IU/month; or 50,000 IU/month. CONCLUSIONS: Large loading doses of vitamin D(3) rapidly and safely normalize 25OHD levels in the frail elderly. Monthly dosing is similarly effective and safe, but takes 3-5 months for plateau 25OHD levels to be reached.

The prevalence of hypovitaminosis D among US adults: data from the NHANES III. Zadshir A, Tareen N, Pan D, Norris K, Martins D. Ethn Dis. 2005 Autumn;15(4 Suppl 5):S5-97-101. PMID: 16315387 CONCLUSION: Serum levels of 25(OH) D3 are below the recommended levels for a large portion of the general adult population and in most minorities. Need exists for a critical review and probable revision of current recommendations for adult vitamin D intake to maintain adequate 25(OH) D3 levels.

Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density. Outila TA, Kärkkäinen MU, Lamberg-Allardt CJ. Am J Clin Nutr. 2001 Aug;74(2):206-10. PMID: 11470722 Conclusion: A large percentage of adolescent females have low vitamin D status during the winter in Finland, which seems to have negative effects on bone health.

Vitamin D status and the risk of lung cancer: a cohort study in Finland. Kilkkinen A, Knekt P, Heliövaara M, Rissanen H, Marniemi J, Hakulinen T, Aromaa A. Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3274-8. PMID: 18990771v In conclusion, although there was no overall association between vitamin D and lung cancer risk, women and young participants with a higher level of vitamin D were observed to have a lower lung cancer risk. Although experimental data support the suppressing effect of vitamin D on the development of lung cancer, large epidemiologic studies from different populations with repeated measurements of vitamin D are warranted to confirm this finding. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3274-8)

March 27, 2009 - A significant decrease in serum 25-hydroxyvitamin D (25[OH]D) levels has led to an increase in vitamin D insufficiency in the US population, especially in racial and ethnic groups, according to results of a population-based study reported in the March 23 issue of the Archives of Internal Medicine. "Vitamin D insufficiency has been associated with increases in cardiovascular disease, cancer, and infection," write Adit A. Ginde, MD, from the Department of Emergency Medicine at the University of Colorado Denver School of Medicine, Aurora, Colorado, and colleagues. "Vitamin D supplementation appears to mitigate the incidence and adverse outcomes of these diseases and may reduce all-cause mortality." [...] "These findings have important implications for health disparities and public health," the study authors conclude. "Our data provide additional evidence that current recommendations for vitamin D supplementation (200-600 IU/d) are inadequate to achieve optimal serum 25(OH)D levels in most of the US population." They add that large, randomized controlled trials of higher doses of vitamin D supplementation are needed to evaluate their effect on general health and mortality.

A large number of new vitamin D studies have appeared in the scientific literature since I wrote my plea to the federal government. These studies don't just confirm what we knew 16 months ago-they show that optimizing vitamin D intake will save even more lives than what we projected. Vitamin D More Effective Than Previously Known For instance, a study published in June 2008 showed that men with low vitamin D levels suffer 2.42 times more heart attacks. Now look what this means in actual body counts.

PLYMOUTH medical researchers have discovered a link between lack of the 'sunshine vitamin' and the onset of dementia.\n\nTeams from the city's Peninsula Medical School and the universities of Cambridge and Michigan have for the first time found a relationship between lower Vitamin D levels and cognitive impairment in older people.\n\nThe results of their large-scale study are to be published in the Journal of Geriatric Psychology and Neurology.

Vitamin D and breast cancer. Bertone-Johnson ER. Ann Epidemiol. 2009 Jul;19(7):462-7. Epub 2009 Feb 20. Review. PMID: 19230714 Though the relationship between vitamin D and breast cancer remains unclear, a growing body of evidence suggests that vitamin D may modestly reduce risk. A large number of in vitro studies indicate that vitamin D can inhibit cell proliferation and promote apoptosis and cell differentiation in breast tumor tissue. Results from analytic studies of sunlight exposure and dietary intake have been inconsistent but together generally support a modestly protective role of vitamin D, at least in some population subgroups. Studies using blood vitamin D metabolites to assess vitamin D status may be less prone to misclassification than those of diet and sunlight exposure. Overall, the two prospective and four case-control studies of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D tend to support a protective effect in older women. The relationship between common vitamin D receptor polymorphisms and risk remains unclear. Many questions about this relationship clearly remain, including the utility of assessing vitamin D through diet and sunlight exposure, the relationship between plasma metabolites, and the potential modifying effects of age, menopausal status and tumor characteristics. Given that vitamin D status is modifiable, additional prospective studies are necessary to determine if vitamin D may have important potential for breast cancer prevention.

Seasonality of UV-radiation and vitamin D status at 69 degrees north. Brustad M, Edvardsen K, Wilsgaard T, Engelsen O, Aksnes L, Lund E. Photochem Photobiol Sci. 2007 Aug;6(8):903-8. Epub 2007 Jun 27. PMID: 17668121 The generally high dietary intakes of vitamin D, especially in winter, mask largely the effect of seasonal variation in UV-exposure, causing an atypical seasonal variation in vitamin D status. The UV-hour variable significantly predicted 25(OH)D levels in blood when adjusted for intakes and artificial UV-radiation exposure and sun holidays abroad.