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Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Low vitamin D status despite abundant sun exposure. Binkley N, Novotny R, Krueger D, Kawahara T, Daida YG, Lensmeyer G, Hollis BW, Drezner MK. J Clin Endocrinol Metab. 2007 Jun;92(6):2130-5. Epub 2007 Apr 10. PMID: 17426097 doi:10.1210/jc.2006-2250 CONCLUSIONS: These data suggest that variable responsiveness to UVB radiation is evident among individuals, causing some to have low vitamin D status despite abundant sun exposure. In addition, because the maximal 25(OH)D concentration produced by natural UV exposure appears to be approximately 60 ng/ml, it seems prudent to use this value as an upper limit when prescribing vitamin D supplementation.

Vitamin D: a D-Lightful health perspective. Holick MF. Nutr Rev. 2008 Oct;66(10 Suppl 2):S182-94. Review. PMID: 18844847 DOI: 10.1111/j.1753-4887.2008.00104.x Sunlight provides most humans with their vitamin D requirement. Adequate vitamin D(3) by synthesis in the skin or from dietary and supplemental sources is essential for bone health throughout life. Vitamin D deficiency is defined as a 25(OH)D concentration 30 ng/mL (75 nmol/L), and insufficiency as 21-29 ng/mL. Vitamin D deficiency and insufficiency has been linked to a wide variety of chronic diseases including common cancers, autoimmune, cardiovascular, and infectious diseases. Healthcare professionals need to be aware of the vitamin D deficiency pandemic. Guidelines for sensible sun exposure and supplemental vitamin D of 800-1000 IU/day are needed.

Upper levels of vitamin D intake were set at 50 microg/d (2000 IU/d) for all ages. Some individuals would require higher levels than these to achieve serum 25-hydroxyvitamin D concentrations for optimal calcium absorption. So much new information on vitamin D and health has been collected since the requirements were set in 1997 that this nutrient is likely the most in need of revised requirements. Vitamin D requirements: current and future. Weaver CM, Fleet JC. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1735S-9S. Review. Erratum in: Am J Clin Nutr. 2005 Mar;81(3):729. PMID: 15585797

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.

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.

Vitamin D Toxicity Fears Unwarranted Is vitamin D toxic? Not if we take the same amount nature intended when we go out in the sun. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentration, and safety. Am J Clin Nutr. 1999;69:842-56. Vieth attempted to dispel unwarranted fears in medical community of physiological doses of vitamin D in 1999 with his exhaustive and well-written review. D-Lite, Renew, & SunSplash UV/Tanning Systems Sunsplash Tanning System Is toxicity a concern for you? If so, then increase your levels the way nature intended, with ultraviolet B light! His conclusions: fear of vitamin D toxicity is unwarranted, and such unwarranted fear, bordering on hysteria, is rampant in the medical profession. Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001 Feb;73(2):288-94. Even Ian Monroe, the chair of the relevant IOM committee, wrote to the Journal to compliment Vieth's work and to promise his findings will be considered at the time of a future Institute of Medicine review. Munro I. Derivation of tolerable upper intake levels of nutrients. Letter, Am J Clin Nutr. 2001;74:865. That was more than two years ago.

Assessment of dietary vitamin D requirements during pregnancy and lactation. Hollis BW, Wagner CL. Am J Clin Nutr. 2004 May;79(5):717-26. Review. PMID: 15113709 We found that high-dose maternal vitamin D supplementation not only improves the nutritional vitamin D status of breastfeeding infants but also elevates the maternal concentrations into the mid-normal range. Thus, a dual benefit is achieved from high-dose maternal supplementation. It is noteworthy that in the Finnish study, the authors added a disclaimer, "A sufficient supply of vitamin D to the breastfed infant is achieved only by increasing the maternal supplementation up to 2000 IU/d. Such a dose is far higher than the RDA [DRI] for lactating mothers [and therefore] its safety over prolonged periods is not known and should be examined by further study." This point of concern was valid when this study was conducted in 1986 (92); however, on the basis of the current findings of Vieth et al (2) and of Heaney et al (3)-which showed that vitamin D intakes <= 10 000 IU/d (250 µg) are safe for prolonged periods (up to 5 mo)-we believe that it is time to reexamine the understated DRI of vitamin D for lactating mothers. This work is now being conducted in our clinics and laboratory.

Contains information how to convert serum 25(OH)D (calcidiol) concentration units nmol/l to ng/ml and vice versa.

Conclusions: Healthy men seem to use 3000-5000 IU cholecalciferol/d, apparently meeting > 80% of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months. Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin D. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Am J Clin Nutr. 2003 Jan;77(1):204-10. Erratum in: Am J Clin Nutr. 2003 Nov;78(5):1047. PMID: 12499343

Vitamin D3 and 25-hydroxyvitamin D3 in raw and cooked pork cuts. Ina Clausen, Jette Jakobsen, Torben Leth and Lars Ovesen. Journal of Food Composition and Analysis Volume 16, Issue 5, October 2003, Pages 575-585 doi:10.1016/S0889-1575(03)00064-4 Meat 25OHD3 contributes significantly to vitamin D activity. Food databases should include concentrations of both vitamin D and 25OHD.

Relationships between 25-Hydroxyvitamin D Levels and Plasma Glucose and Lipid Levels in Pediatric Outpatients. Johnson MD, Nader NS, Weaver AL, Singh R, Kumar S. J Pediatr. 2009 Nov 17. [Epub ahead of print] PMID: 19926097 Conclusions Low 25(OH) D levels in children and adolescents are associated with higher plasma glucose and lower HDL concentrations.

Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial. von Hurst PR, Stonehouse W, Coad J. Br J Nutr. 2009 Sep 28:1-7. [Epub ahead of print] PMID: 19781131 In conclusion, improving vitamin D status in insulin resistant women resulted in improved IR and sensitivity, but no change in insulin secretion. Optimal vitamin D concentrations for reducing IR were shown to be 80-119 nmol/l, providing further evidence for an increase in the recommended adequate levels. Registered Trial No. ACTRN12607000642482.

Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, Arden NK, Godfrey KM, Cooper C; Princess Anne Hospital Study Group. Lancet. 2006 Jan 7;367(9504):36-43. Erratum in: Lancet. 2006 May 6;367(9521):1486. PMID: 16399151 doi:10.1016/S0140-6736(06)67922-1 Interpretation Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium. Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.

"Kuluttajille on eräillä keskustelufoorumeilla yritelty uskotella, että öljypohjaiset D-vitamiinivalmisteet omaavat paremman biologisen hyväksikäytettävyyden kuin D-vitamiinitabletit, mutta tälle väitteelle ei löydy mitään tukea tieteellisestä kirjallisuudesta. Norjalaistutkimuksessa verrattiin D3-vitamiinia sisältävät multivitamiinitabletin ja D3-vitamiinia sisältävän kalaöljykapselin vaikutuksia seerumin (veren) 25-OH-D-vitamiinipitoisuuteen (S-25(OH)D). Koehenkilöt saivat neljän viikon ajan 10 mikrogrammaa D3-vitamiinia joko tableteista tai öljykapseleista. Tablettiryhmässä S-25(OH)D-pitoisuus nousi keskimäärin 35,8 nmol/l ja kapseliryhmässä 32,3 nmol/l. "We conclude that fish oil capsules and multivitamin tablets containing 10 microg cholecalciferol administered over a 4-week period produced a similar mean increase in s-25(OH)D concentration", päättelivät tutkijat. Vuotta aiemmin julkaistussa suomalaistutkimuksessa havaittiin, että D3-vitamiini imeytyy erilaisista leivistä samalla tehokkuudella kuin D-vitamiinivalmisteesta. Kanadalaistutkijat raportoivat juuston osalta samanlaisia tuloksia. Vuonna 2003 jenkkitutkijat totesivat, että "fat is not required for vitamin D to be bioavailable." Mainittakoon lopuksi, että D3-vitamiinitabletteihin lisätään yleensä D3-vitamiinivalmistetta, jossa on öljy jo valmiina. Ainesosaluetteloissa lukee lähes säännönmukaisesti "D3-vitamiinivalmiste" ja sen jälkeen suluissa pelkkä aktiiviaine eli "kolekalsiferoli" tai "sisältää mm. kolekalsiferolia ja soijaöljyä" tai jotain vastaavaa. Tämä D3-vitamiinivalmiste on sitten ympäröity täyteaineilla, jotka eivät vaikuta D3-vitamiinin imeytymiseen millään tavalla. Tabletti hajoaa hyvin nopeasti maha-suolikanavassa."

Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese. Pan A, Lu L, Franco OH, Yu Z, Li H, Lin X. J Affect Disord. 2009 Nov;118(1-3):240-3. Epub 2009 Feb 27. PMID: 19249103 doi:10.1016/j.jad.2009.02.002 Conclusions Depressive symptoms are not associated with 25(OH)D concentrations in middle-aged and elderly Chinese. Further prospective studies are required to determine whether they are correlated.

Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J. BMJ. 2009 Oct 1;339:b3692. doi: 10.1136/bmj.b3692. PMID: 19797342 doi: 10.1136/bmj.b3692 Conclusions Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.

Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Chirlaque MD, Barricarte A, Larrañaga N, González CA, Argüelles MV, Sánchez MJ, Stattin P, Hallmans G, Khaw KT, Bingham S, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ. Am J Epidemiol. 2009 May 15;169(10):1223-32. Epub 2009 Apr 9. PMID: 19359375 In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.

Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. Heikkinen AM, Tuppurainen MT, Niskanen L, Komulainen M, Penttilä I, Saarikoski S. Eur J Endocrinol. 1997 Nov;137(5):495-502. PMID: 9405029 CONCLUSIONS: Our results confirm the positive long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin D3 treatment was associated with increased serum LDL cholesterol. Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D3. However, the relevance of these associations to cardiovascular morbidity remains to be established.