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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

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.

Table of Contents Ch. I Is calcidiol an active hormone? 1 Ch. II Vitamin D as a neurosteroid hormone : from neurobiological effects to behavior 29 Ch. III Inhibitors of vitamin D hydroxylases : mechanistic tools and therapeutic aspects 67 Ch. IV Vitamin D analogues as anti-cancer therapies 145 Ch. V Paricalcitol : a vitamin D2 analog with anticancer effects with low calcemic activity 169 Ch. VI Vitamin D use among older adults in U.S. : results form national surveys 1997 to 2002 181 Ch VII Vitamin D deficiency in migrants 199 Vitamin D is a fat-soluble steroid hormone precursor that contributes to the maintenance of normal levels of calcium and phosphorus in the bloodstream. Strictly speaking, it is not a vitamin since human skin can manufacture it, but it is referred to as one for historical reasons. It is often known as calciferol. The major biologic function of vitamin D is to maintain normal blood levels of calcium and phosphorus. Vitamin D aids in the absorption of calcium, helping to form and maintain strong bones. It promotes bone mineralisation in concert with a number of other vitamins, minerals and hormones. Without vitamin D, bones can become thin, brittle, soft or misshapen. Vitamin D prevents rickets in children and osteomalacia in adults -- skeletal diseases that result in defects that weaken bones. This book gathers international research on the leading-edge of the scientific front.

Acid-base balance has an effect on bone turnover, especially on the rates of bone resorption and calcium mobilization. Bone mineral participates in the defense against acid-base disturbances, especially against metabolic acidosis (Lemann et al. 1966, Green & Kleeman 1991). The role of the bone mineral is important in the acid-base disorders, as no appreciable change in the intestinal calcium absorption occurs (Bichara et al. 1990). In the mammalian body, mainly three hormones regulate the calcium metabolism and the bone turnover. 1,25-dihydroxycholecalciferol (vitamin D derivative) increases calcium absorption from the intestine and, indirectly, from bone. Parathyroid hormone mobilizes calcium from the bone and increases the urinary phosphate excretion. Calcitonin inhibits bone resorption (Ganong 1981). Used as drugs, these hormones are also capable of inducing acid-base disorders. Calcitonin administration (Escanero et al. 1991) and vitamin D excess (Bichara et al. 1990) have been reported to cause metabolic alkalosis.

A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls - a cross-sectional study. Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. Br J Nutr. 2006 Jul;96(1):124-30. PMID: 16870000 Seasonal variation in S-25-OHD and bone remodelling markers accompanied by negative correlation between S-25-OHD and S-iPTH was seen in this cross-sectional study of adolescent girls. In addition, the seasonal rhythm contributed 7.0-7.6 % difference in the BMD of lumbar vertebrae and left femur in early puberty girls. This variation should be avoided since it could hamper peak bone mass attainment.

25-hydroxyvitamin D3 is an active hormone in human primary prostatic stromal cells. Lou YR, Laaksi I, Syvälä H, Bläuer M, Tammela TL, Ylikomi T, Tuohimaa P. FASEB J. 2004 Feb;18(2):332-4. Epub 2003 Dec 4. PMID: 14657005

Comment: Although lower risk associated with vitamin D exposure was shown most consistently for ER+/PR+ tumors, the result might simply reflect that this tumor subtype was the most common. Nonetheless, these findings support vitamin D's beneficial effects on breast cancer risk, regardless of hormone-receptor status. Sun exposure and dietary intake (Table 1) are key sources of vitamin D.

Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer. Blackmore KM, Lesosky M, Barnett H, Raboud JM, Vieth R, Knight JA. Am J Epidemiol. 2008 Oct 15;168(8):915-24. Epub 2008 Aug 27. PMID: 18756015 doi:10.1093/aje/kwn198 This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor. Future studies with a larger number of receptor-negative and mixed tumors are required.

Why "Vitamin D" is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids. Vieth R. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):571-3. PMID: 15225841 doi:10.1016/j.jsbmb.2004.03.037

Reinehr T, de Sousa G, Alexy U, Kersting M, Andler W. Vitamin D status and parathyroid hormone in obese children before and after weight loss. Eur J Endocrinol. 2007 Aug;157(2):225-32. PMID: 17656603 [PubMed - in process]

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.

Vitamin D, nervous system and aging. P. Tuohimaa, T. Keisala, A. Minasyan, J. Cachat and A. Kalueff. . Psychoneuroendocrinology, Volume 34, Supplement 1, December 2009, Pages S278-S286 NEUROACTIVE STEROIDS: EFFECTS AND MECHANISMS OF ACTION doi:10.1016/j.psyneuen.2009.07.003 This is a mini-review of vitamin D3, its active metabolites and their functioning in the central nervous system (CNS), especially in relation to nervous system pathologies and aging. The vitamin D3 endocrine system consists of 3 active calcipherol hormones: calcidiol (25OHD3), 1α-calcitriol (1α,25(OH)2D3) and 24-calcitriol (24,25(OH)2D3). The impact of the calcipherol hormone system on aging, health and disease is discussed. Low serum calcidiol concentrations are associated with an increased risk of several chronic diseases including osteoporosis, cancer, diabetes, autoimmune disorders, hypertension, atherosclerosis and muscle weakness all of which can be considered aging-related diseases. The relationship of many of these diseases and aging-related changes in physiology show a U-shaped response curve to serum calcidiol concentrations. Clinical data suggest that vitamin D3 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. 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 calcipherol system appear to cause abnormal function, including premature aging, of the CNS.

My doctor advised us to give Vitamin D to both our children, though our son is more than 4 year old. I decided to find out more about it. I surfed the Internet, read the description of the vitamin (here Canadian Pharmacy site https://www.canadapharmacy.com/ helped me a lot). Finally, I decided to give it to my children. But I didn't know, it is good for adults. Thanks for sharing this information, it is very useful for me!

Wintertime vitamin D supplementation inhibits seasonal variation of calcitropic hormones and maintains bone turnover in healthy men. Viljakainen HT, Väisänen M, Kemi V, Rikkonen T, Kröger H, Laitinen EK, Rita H, Lamberg-Allardt C. J Bone Miner Res. 2009 Feb;24(2):346-52. PMID: 18847321

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

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Cardiovasc Diabetol. 2009 Feb 3;8:7. PMID: 19187564 doi:10.1186/1475-2840-8-7 CONCLUSION: The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.

Association of low 25-hydroxyvitamin D concentrations with elevated parathyroid hormone concentrations and low cortical bone density in early pubertal and prepubertal Finnish girls. Cheng S, Tylavsky F, Kröger H, Kärkkäinen M, Lyytikäinen A, Koistinen A, Mahonen A, Alen M, Halleen J, Väänänen K, Lamberg-Allardt C. Am J Clin Nutr. 2003 Sep;78(3):485-92. Erratum in: Am J Clin Nutr. 2006 Jan;83(1):174. PMID: 12936933 CONCLUSIONS: Vitamin D-deficient girls have low cortical BMD and high iPTH concentrations, which are consistent with secondary hyperparathyroidism. A low vitamin D concentration accompanied by high bone resorption (TRAP 5b) may limit the accretion of bone mass in young girls.

A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, Mononen I. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):152-7. Epub 2007 Jun 19. PMID: 17578859 doi:10.1136/jnnp.2006.105320 Conclusions: The endocrine circuitry regulating serum calcium may be altered in MS. There is an inverse relationship between serum vitamin D level and MS clinical activity. The role of vitamin D in MS must be explored further.

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.

Human lung tumors have the ability to eliminate Vitamin D, a hormone with anti-cancer activity, a new study from the University of Pittsburgh Cancer Institute (UPCI) suggests. Results of the study are being presented at the 100th annual meeting of the American Association for Cancer Research (AACR), April 18 to 22, in Denver.

Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Hoogendijk WJ, Lips P, Dik MG, Deeg DJ, Beekman AT, Penninx BW. Arch Gen Psychiatry. 2008 May;65(5):508-12. PMID: 18458202 Conclusion The results of this large population-based study show an association of depression status and severity with decreased serum 25(OH)D levels and increased serum PTH levels in older individuals.