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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.

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.

Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD. J Clin Endocrinol Metab. 2008 Mar;93(3):677-81. Epub 2007 Dec 18. PMID: 18089691 Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

"I discussed in my last post how Dr Vieth has a model of tissue 1,25(OH)2D synthesis and degradation in which the level of active substance is pretty well independent of blood vitamin D level, provided the level is either rising or stable. I think it is also worth pointing out that he is talking, hypothetically, about tissue 1,25(OH)2D, not plasma level... As we know, almost nothing is known about tissue 1,25(OH)2D control. By Vieth's hypothesis tissue 1,25(OH)2D is OK so long as there is at least SOME vitamin D present in plasma and the level dose not vary too much. Obviously there is a level below which you can have as much of the enzyme for converting vitamin D to the active form as you like, if there is no vitamin D in your blood you can't make any 1,25(OH)2D in your tissues, or in your kidneys for export to your blood to control calcium levels. At the lower extremes we have rickets and osteomalacia. These are clear cut, unarguable markers of vitamin D deficiency, in the absence of confounding factors (there are a few)."

Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD. Bone. 2009 Nov;45(5):870-5. Epub 2009 Jul 23. PMID: 19631774 doi:10.1016/j.bone.2009.07.015 Cholecalciferol supplementation resulted in a 31% greater increase in total HPLC-measured 25OHD (p=0.010) and 52% greater rise in RIA-measured 25OHD (p0.05). In vitamin D-insufficient hip fracture patients, supplementation with cholecalciferol 1000 IU/day for three months was more effective in increasing serum 25OHD than an equivalent dose of ergocalciferol. However, the lack of difference in PTH lowering between calciferol treatments raises questions about the biological importance of this observation.

Concentrations of vitamin D3 and 25-hydroxyvitamin D3 in raw and cooked New Zealand beef and lamb. Roger Purchas, Maggie Zoua, Philip Pearcea and Felicity Jackson- Journal of Food Composition and Analysis Volume 20, Issue 2, March 2007, Pages 90-98 For lamb, the highest levels of vitamin D3 were in the shoulder chop both before and after cooking, while levels were lowest in the rack muscle. Similar cut differences were shown for 25OHD3 concentrations. For beef there were no significant differences between the cuts for vitamin D3, but concentrations of 25OHD3 were lower in the striploin before and after cooking, Vitamin D3 levels tended to be higher in beef cuts than in lamb cuts, but the opposite held for 25OHD3. Concentrations of vitamin D3 were similar to those in other reports, but the 25OHD3 levels were at the high end of reported ranges. With 25OHD3 being more potent than vitamin D3, it is concluded that meat can make a useful contribution of this vitamin to the human diet.

Serum vitamin D level after an annual intramuscular injection of ergocalciferol. Heikinheimo RJ, Haavisto MV, Harju EJ, Inkovaara JA, Kaarela RH, Kolho LA, Rajala SA. Calcif Tissue Int. 1991;49 Suppl:S87. PMID: 1933611 An annual intramuscular injection of ergocalciferol (150,000 IU) normalized low serum (25(OH)D concentrations in elderly people for 1 year. The treatment had a slight effect on serum 24,25(OH)2D levels but no effect on 1,25(OH)2D levels.

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

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.

Severe vitamin D deficiency in Swiss hip fracture patients. Bischoff-Ferrari HA, Can U, Staehelin HB, Platz A, Henschkowski J, Michel BA, Dawson-Hughes B, Theiler R. Bone. 2008 Mar;42(3):597-602. Epub 2007 Nov 28. PMID: 18180211 BACKGROUND: Most clinical guidelines for the prevention of hip fractures recommend 800 IU vitamin D per day. This dose shifted serum 25-hydroxyvitamin D levels (25(OH)D) in previous studies to between 60 and 100 nmol/l. AIM: To measure 25(OH)D levels and prevalence of vitamin D supplementation in individuals age 65+ with acute hip fracture. METHODS: 222 consecutive hip fracture patients were investigated over a 12 month period. Mean age of patients was 86 years and 77% were women. RESULTS: Mean serum 25(OH)D levels were low among hip fracture patients admitted from home (34.6 nmol/l), from assisted living (27.7 nmol/l), and from nursing homes (24 nmol/l). Severe vitamin D deficiency below 30 nmol/l was present in 60%, 80% were below 50 nmol/l, and less than 4% reached desirable levels of at least 75 nmol/l. Consistently, only 10% of hip fracture patients had any vitamin D supplementation on admission to acute care with significantly higher 25(OH)D levels among individuals supplemented with 800-880 IU/day (63.5 nmol/l). Controlling for age and gender, vitamin D supplementation, type of dwelling, and season were independently and significantly associated with 25(OH)D levels. CONCLUSION: These data provide evidence that current guidelines for the prevention of hip fractures need further effort to be translated into clinical practice.

Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Jorde R, Figenschau Y. Eur J Nutr. 2009 Apr 16. [Epub ahead of print] PMID: 19370371 10.1007/s00394-009-0020-3 Conclusions We were not able to demonstrate that vitamin D supplementation had a significant effect on glucose metabolism in subjects with type 2 diabetes but without vitamin D deficiency. Further studies are needed in larger groups of subjects with type 2 diabetes or impaired glucose tolerance, who also exhibit low serum 25-hydroxyvitamin D levels.

Why would vitamin D be prescribed when vitamin D3 is available over-the-counter? Let's review the known differences between vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol): --D3 is the human form; D2 is the non-human form found in plants. --Dose for dose, D3 is more effective at raising blood levels of 25-hydroxy vitamin D than D2. It requires roughly twice to 250% of the dose of D2 to match that of D3 (Trang H et al 1998). --D2 blood levels don't yield long-term sustained levels of 25-hydroxy vitamin D as does D3. When examined as a 28-day area under the curve (AUC--a superior measure of biologic exposure), D3 yields better than a 300% increased potency compared to D2. This means that it requires around 50,000 units D2 to match the effects of 15,000 units D3 (Armas LA et al 2004). --D2 has lower binding affinity for vitamin D-binding protein, compared to D3 --Mitochondrial vitamin D 25-hydroxylase converts D3 to the 25-hydroxylated form five times more rapidly than D2. --As we age, the ability to metabolize D2 is dramatically reduced, while D3 is not subject to this phenomenon

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.

"ScienceDaily (Oct. 8, 2009) - Women with breast cancer should be given high doses of vitamin D because a majority of them are likely to have low levels of vitamin D, which could contribute to decreased bone mass and greater risk of fractures, according to scientists at the University of Rochester Medical Center." Scientists funded by the NCI analyzed vitamin D levels in each woman, and the average level was 27 nanograms per milliliter; more than two-thirds of the women had vitamin deficiency. Weekly supplementation with high doses of vitamin D -- 50,000 international units or more -- improved the levels, according to Peppone's study. The U.S. Institute of Medicine suggests that blood levels nearing 32 nanograms per milliliter are adequate.

"* Low levels of vitamin D were associated with increased risk of high blood pressure, high blood sugar and metabolic syndrome in teenagers. * The highest levels of vitamin D were found in whites, the lowest levels in blacks and intermediate levels in Mexican-Americans. PALM HARBOR, Fla., March 11, 2009 - Low levels of vitamin D were associated with an increased risk of high blood pressure, high blood sugar and metabolic syndrome in teenagers, researchers reported at the American Heart Association's 49th Annual Conference on Cardiovascular Disease Epidemiology and Prevention."

Statins and vitamin D. Aloia JF, Li-Ng M, Pollack S. Am J Cardiol. 2007 Oct 15;100(8):1329. Epub 2007 Jul 5. No abstract available. PMID: 17920383 A total of 208 women were randomized to receive vitamin D3 (n=104) or placebo (n=104). 51 women were on statins. At baseline, the subjects on statins had a significantly higher 25-OHD level than the subjects who were not on statins (51.2 ± 20.1 nmol/L versus 43.2 ± 18.0 nmol/L respectively, p=0.008). This was also true when averaging 25-OHD levels across the 3-year study period and looking at active and placebo patients separately. 185 subjects had follow-up 25-OHD levels drawn every 6 months during the study. Higher levels were seen in the statin use subgroup whether they were on placebo or active vitamin D (Figure 1Figure 1). There was no interaction seen between vitamin D use and statin use, i.e. the impacts are additive (p=0.5502). This significant difference is comparable to the increase in 25-OHD levels seen in Pérez-Castrillón's study (41 ± 19 versus 47 ± 19 nmol/L, p=0.003) [1]. Although Pérez-Castrillón et al found a statistically significant relation between total cholesterol and 25-OHD (r=0.277, p=0.002), we did not find a significant relation between total cholesterol and 25-OHD in our study population.

Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic. Cannell JJ, Vieth R, Willett W, Zasloff M, Hathcock JN, White JH, Tanumihardjo SA, Larson-Meyer DE, Bischoff-Ferrari HA, Lamberg-Allardt CJ, Lappe JM, Norman AW, Zittermann A, Whiting SJ, Grant WB, Hollis BW, Giovannucci E. Ann Otol Rhinol Laryngol. 2008 Nov;117(11):864-70. Review. PMID: 19102134 Until we have better information on doses of vitamin D that will reliably provide adequate blood levels of 25(OH)D without toxicity, treatment of vitamin D deficiency in otherwise healthy children should be individualized according to the numerous factors that affect 25(OH)D levels, such as body weight, percent body fat, skin melanin, latitude, season of the year, and sun exposure.2 The doses of sunshine or oral vitamin D3 used in healthy children should be designed to maintain 25(OH)D levels above 50 ng/mL. As a rule, in the absence of significant sun exposure, we believe that most healthy children need about 1,000 IU of vitamin D3 daily per 11 kg (25 lb) of body weight to obtain levels greater than 50 ng/mL. Some will need more, and others less. In our opinion, children with chronic illnesses such as autism, diabetes, and/or frequent infections should be supplemented with higher doses of sunshine or vitamin D3, doses adequate to maintain their 25(OH)D levels in the mid-normal of the reference range (65 ng/mL) - and should be so supplemented year round. Otolaryngologists treating children are in a good position to both diagnose and treat vitamin D deficiency.

"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."

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.

Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol. Vieth R, Milojevic S, Peltekova V. J Nutr. 2000 Mar;130(3):578-84. PMID: 10702588 We conclude suppression of 1,25(OH)(2)D and PTH, and higher renal VDR mRNA and 24-hydroxylase did not involve higher free 1,25(OH)(2)D concentration or a first pass effect at the gut. Thus, 25(OH)D or a metabolite other than 1,25(OH)(2)D is a physiological, transcriptionally and biochemically active, noncalcemic vitamin D metabolite. When viewed from a perspective that starts with higher vitamin D nutrition, the results indicate that low vitamin D nutrition may bring about a form of resistance to 1,25(OH)2D. This situation would explain why, in humans, nutritional rickets and osteomalacia are commonly associated with normal or increased levels of 1,25(OH)2D (Chesney et al. 1981Citation , Eastwood et al. 1979Citation , Garabedian et al. 1983Citation ,Rasmussen et al. 1980Citation )-these are not like the low hormone levels associated with any other endocrine-deficiency disorder. A connection between lower vitamin D nutrition and vitamin D resistance helps to explain why the supposedly inactive compound 25(OH)D is more relevant in diagnosing nutritional rickets than is the active hormone 1,25(OH)2D. If the features of improved vitamin D nutrition shown here were demonstrated for any newly synthesized compound, the compound would be classified as a noncalcemic 1,25(OH)2D analogue (Brown et al. 1989Citation , Finch et al. 1999Citation , Goff et al. 1993Citation , Koshizuka et al. 1999Citation ). Thus, we contend that 25(OH)D or a metabolite of it other than 1,25(OH)2D exists as a physiological and biologically-active noncalcemic vitamin D metabolite whose effects require further examination, particularly in relationship to studies involving the synthetic analogs of 1,25(OH)2D.