Group items tagged

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A. Am J Cardiol. 2007 Apr 1;99(7):903-5. Epub 2007 Feb 8. PMID: 17398180 In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. The mechanism by which atorvastatin increases vitamin D levels is related to inhibition of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol is synthesized from 7-dehydrocholesterol, which is also a precursor of vitamin D3. For this reason, we initially observed a statistically significant relation between total cholesterol and vitamin D. HMG-CoA enzyme reductase is key to the synthesis of cholesterol, whereas ultraviolet radiation causes the formation of 25-hydroxyvitamin D. Inhibition of the enzyme may increase levels of 7-dehydrocholesterol and increase the synthesis of 25-hydroxycholecalciferol, thereby increasing vitamin D levels,10 although we observed no relation between lower cholesterol and increased vitamin D. In addition, 25-hydroxyvitamin D has been shown to inhibit HMG-CoA enzyme reductase activity in in vitro studies.11 A greater concentration of vitamin D could increase enzymatic inhibition, acting in synergy with the statin in decreasing total cholesterol.

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Chen W, Dawsey SM, Qiao YL, Mark SD, Dong ZW, Taylor PR, Zhao P, Abnet CC. Br J Cancer. 2007 Jul 2;97(1):123-8. Epub 2007 Jun 5. PMID: 17551495 We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result. In conclusion, we found a direct association between higher serum 25(OH)D concentration and increased risk of ESCC in men but not women in a large population-based prospective cohort study from rural China. We found no association with risk of gastric cardia or noncardia adenocarcinoma in either sex. Greater than 50% of our cohort had an inadequate serum 25(OH)D concentration, yet higher concentrations were associated with increased risk of ESCC compared to lower concentrations.

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.

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.

Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, Lu N, Taylor PR, Qiao YL. Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1889-93. PMID: 17855710 doi: 10.1158/1055-9965.EPI-07-0461 Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. Conclusions: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. In conclusion, we found that a higher serum 25(OH)D concentration was associated with an increased risk of esophageal squamous dysplasia, the precursor lesion for ESCC. This finding concurs with our previous prospective study which found that higher vitamin D status was associated with increased risk of incident ESCC in this same population. These unexpected findings suggest that further studies of the association of vitamin D and digestive tract cancers are needed before the effect of vitamin D in different populations can be elucidated.

"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."

Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. Vieth R, Ladak Y, Walfish PG. J Clin Endocrinol Metab. 2003 Jan;88(1):185-91. PMID: 12519850 This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function

Not enough vitamin D: health consequences for Canadians. Schwalfenberg G. Can Fam Physician. 2007 May;53(5):841-54. Review PMID: 17872747 Conclusion Low levels of VTD are considered a major public health problem in Canada, especially during the winter. Those with risk factors should be screened for low 25(OH)D levels and repletion therapy instituted if needed. Researchers have estimated that the oral dose of vitamin D3 to attain and maintain 25(OH)D levels >80 nmol/L is 2200 IU/d if baseline levels are 20 to 40 nmol/L, 1800 IU/d if levels are 40 to 60 nmol/L, and 1160 IU/d if levels are between 60 and 80 nmol/L.64 We need to ensure that patients have healthy blood levels of 25(OH)D to prevent levels of parathyroid hormone from rising and to maximize absorption of calcium, magnesium, and phosphate. Positive effects on bone are marginal at best unless patients consume at least 800 IU/d of VTD. The emerging and exciting role of the VTD receptor and the actions of VTD in maintaining health in other cell types have become more apparent during the last decade.

Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. Kovacs CS. Am J Clin Nutr. 2008 Aug;88(2):520S-528S. Review. PMID: 18689394 Dosing recommendations for women during pregnancy and lactation might be best directed toward ensuring that the neonate is vitamin D-sufficient and that this sufficiency is maintained during infancy and beyond. A dose of vitamin D that provides 25(OH)D sufficiency in the mother during pregnancy should provide normal cord blood concentrations of 25(OH)D. Research has shown that during lactation, supplements administered directly to the infant can easily achieve vitamin D sufficiency; the mother needs much higher doses (100 µg or 4000 IU per day) to achieve adult-normal 25(OH)D concentrations in her exclusively breastfed infant. In addition, the relation (if any) of vitamin D insufficiency in the fetus or neonate to long-term nonskeletal outcomes such as type 1 diabetes and other chronic diseases needs to be investigated.

Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism. The active form of vitamin D binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. The major carrier is called, appropriately, vitamin D-binding protein. The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours. The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1,25-dihydroxycholecalciferol is roughly 1000 times that for 25-hydroxycholecalciferol, which explains their relative biological potencies

Vitamin D and type 2 diabetes: are we ready for a prevention trial? Scragg R. Diabetes. 2008 Oct;57(10):2565-6. PMID: 18820212 doi: 10.2337/db08-0879 Despite evidence from the current article (3) and the Finnish study (17), doubts still remain about whether low vitamin status is a cause of type 2 diabetes. Further cohort studies are required, assessing baseline vitamin D status using blood 25(OH)D to be sure that the Ely and Finnish studies are not false-positive results. Glucose clamp studies are also required because we are still not sure of the mechanism influenced by vitamin D-whether it is insulin resistance, secretion, or both. But most importantly, given that nearly three decades have passed since the first studies linking vitamin D with insulin metabolism (6,7), well-designed clinical trials of the effect of vitamin D supplementation on glycemia status and diabetes risk are urgently required to settle this question. And they need to prevent past mistakes. In particular, the vitamin D dose given in such trials needs to be high enough-above 2,000 IU per day (19)-to raise blood 25(OH)D levels above 80 nmol/l because diabetes risk is lowest at this level (9,20). If well-designed trials are carried out and confirm a protective effect from vitamin D, it could be used by the general population as a simple and cheap solution to help prevent the diabetes epidemic.

Diagnosis and treatment of vitamin D deficiency. Cannell JJ, Hollis BW, Zasloff M, Heaney RP. Expert Opin Pharmacother. 2008 Jan;9(1):107-18. PMID: 18076342 The recent discovery - in a randomised, controlled trial - that daily ingestion of 1100 IU of colecalciferol (vitamin D) over a 4-year period dramatically reduced the incidence of non-skin cancers makes it difficult to overstate the potential medical, social and economic implications of treating vitamin D deficiency. Not only are such deficiencies common, probably the rule, vitamin D deficiency stands implicated in a host of diseases other than cancer. The metabolic product of vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone that targets > 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. A common misconception is that government agencies designed present intake recommendations to prevent or treat vitamin D deficiency. They did not. Instead, they are guidelines to prevent particular metabolic bone diseases. Official recommendations were never designed and are not effective in preventing or treating vitamin D deficiency and in no way limit the freedom of the physician - or responsibility - to do so. At this time, assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis and to assure that treatment is adequate and safe. The authors believe that treatment should be sufficient to maintain levels found in humans living naturally in a sun-rich environment, that is, > 40 ng/ml, year around. Three treatment modalities exist: sunlight, artificial ultraviolet B radiation or supplementation. All treatment modalities have their potential risks and benefits. Benefits of all treatment modalities outweigh potential risks and greatly outweigh the risk of no treatment. As a prolonged 'vitamin D winter', centred on the winter solstice, occurs at many temperate latitudes, ≤ 5000 IU (125 μg) of vitamin D/d

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.

Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D ≤ 80 nmol or 32 µg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. Hollis BW. J Nutr. 2005 Feb;135(2):317-22. Review. PMID: 15671234 [

Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Vieth R. Ann Epidemiol. 2009 Jul;19(7):441-5. Epub 2009 Apr 11. Review. PMID: 19364661 Conclusion The results of well-conducted trials of vitamin D lead to the conclusion that the current U.S. National Academy of Sciences-Institute of Medicine upper limit for vitamin D intake of 2000IU per day 1, 37 is excessively conservative. That intake would raise serum 25(OH)D by an average of about 50 nmol/L (20 ng/mL), well within the safe range of serum 25(OH)D concentrations that extends to 500 nmol/L (200 ng/mL). Intake of 4,000IU per day would raise serum 25(OH)D by an average of about 100 nmol/L (40 ng/mL). Even prolonged physiologic-replacement intake of 10,000IU per day of vitamin D3 would pose no known risk of adverse effects in virtually all adults.

Why is it that vitamin D deficiency can manifest in so many different ways in different people? One big reason is something called vitamin D receptor (VDR) genotypes, the variation in the receptor for vitamin D. Why is it that the dose of vitamin D necessary to reach a specific level differs so widely from one person to the next? VDR genotype, again. Variation in blood levels of 25-hydroxy vitamin D from a specific dose of vitamin D can vary three-fold, as shown by a University of Toronto study. In other words, a dose of 4000 units per day may yield a 25-hydroxy vitamin D blood level of 30 ng/ml in Mary, 60 ng/ml in Paul, and 90 ng/ml in Pete--same dose, different blood levels

Defining Adequate Vitamin D Intake : Cross-sectional and Intervention Studies Viljakainen, Heli Tuulikki University of Helsinki 2008-05-23 Doctoral dissertation (article-based) Vitamin D is required for normal bone growth and maintenance of the skeleton throughout life. In Finland, like in many other Western countries, the population suffers from inadequate or deficient vitamin D status, especially during winter, which is thought to increase the risk of osteoporosis. New strategies to prevent osteoporosis are actively being sought. The main objective of this thesis was to determine whether vitamin D is feasible in the primary prevention of osteoporosis; does it affect bone mineral accrual during the growth period? A second goal was to ascertain whether seasonal variation in calcitropic hormones affects bone remodelling, and to elucidate the vitamin D intake needed to overcome this variation in different age groups. In summary, vitamin D intake remains inadequate among the target groups of this thesis, as reflected by seasonal variation in calcitropic hormones and bone metabolism. Dietary intake of vitamin D should be increased to achieve at least an adequate vitamin D status (S-25-OHD>50 nmol/l) and possibly an optimal vitamin D status (S-25-OHD>80 nmol/l) throughout the year. This could be accomplished by introducing new vitamin D-fortified foods to the market."

Differences in vitamin D status between countries in young adults and the elderly. McKenna MJ. Am J Med. 1992 Jul;93(1):69-77. PMID: 1385673 PURPOSE: To compare vitamin D status between countries in young adults and in the elderly. MATERIALS AND METHODS: Reports on vitamin D status (as assessed by serum 25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped according to geographic regions: North America (including Canada and the United States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and Central and Western Europe (including Belgium, France, Germany, Ireland, The Netherlands, Switzerland, and the United Kingdom). RESULTS: Vitamin D status varies with the season in young adults and in the elderly, and is lower during the winter in Europe than in both North America and Scandinavia. Oral vitamin D intake is lower in Europe than in both North America and Scandinavia. Hypovitaminosis D and related abnormalities in bone chemistry are most common in elderly residents in Europe but are reported in all elderly populations. CONCLUSIONS: The vitamin D status in young adults and the elderly varies widely with the country of residence. Adequate exposure to summer sunlight is the essential means to ample supply, but oral intake augmented by both fortification and supplementation is necessary to maintain baseline stores. All countries should adopt a fortification policy. It seems likely that the elderly would benefit additionally from a daily supplement of 10 micrograms of vitamin D.

Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Lancet. 1989 Nov 18;2(8673):1176-8. PMID: 2572900 Blood samples taken in 1974 in Washington County, Maryland, from 25 620 volunteers were used to investigate the relation of serum 25-hydroxyvitamin D (25-OHD) with subsequent risk of getting colon cancer. 34 cases of colon cancer diagnosed between August, 1975, and January, 1983, were matched to 67 controls by age, race, sex, and month blood was taken. Risk of colon cancer was reduced by 75% in the third quintile (27-32 ng/ml) and by 80% in the fourth quintile (33-41 ng/ml) of serum 25-OHD. Risk of getting colon cancer decreased three-fold in people with a serum 25-OHD concentration of 20 ng/ml or more. The results are consistent with a protective effect of serum 25-OHD on colon cancer.

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.